We put forward a co-axial pump(optical)-probe(X-rays) experimental concept and show performance of the optical component. A Bessel beam generator with a central 100 micrometers-diameter hole (on the optical axis) was fabricated using femtosecond (fs) laser structuring inside a silica plate. This flat-axicon optical element produces a needle-like axial intensity distribution which can be used for the optical pump pulse. The fs-X-ray free electron laser (X-FEL) beam of sub-1 micrometer diameter can be introduced through the central hole along the optical axis onto a target as a probe. Different realisations of optical pump are discussed. Such optical elements facilitate alignment of ultra-short fs-pulses in space and time and can be used in light-matter interaction experiments at extreme energy densities on the surface and in the volume of targets. Full advantage of ultra-short 10 fs X-FEL probe pulses with fs-pump(optical) opens an unexplored temporal dimension of phase transitions and the fastest laser-induced rates of material heating and quenching. A wider field of applications of fs-laser-enabled structuring of materials and design of specific optical elements for astrophotonics is presented.

Electrical properties of the thin films of poly(arylene ether ketone) copolymers (co-PAEKs) with the fraction of phthalide-containing units of 3, 5 and 50 mol% in the main chain were investigated by using radiation induced conductivity (RIC) measurements. Transient current signals and current-voltage (I-V) characteristics were obtained under exposing 20÷25 thick films of the co-PAEKs to monoenergetic electron pulses of the energy ranged from 3 to 50 keV in the electric field ranged from 5 to 40 V/μm. The Rose-Fowler-Vaisberg semi-empirical model based on a multiple trapping formalism was used for an analysis of the RIC data and the parameters of the highly dispersive charge carrier transport were evaluated. The analysis revealed that charge carriers moved in isolation from each other and the applied electric fields were below the threshold field triggering the switching effect (a reversible high-to-low resistivity transition) in the co-PAEK films. It was also found that the co-PAEK films due to the super-linear I-V characteristics are highly resistant to electrostatic discharges arising from the effects of ionizing radiation. This property is important for the development of protective coatings for electronic devices.

In this work, we focus on investigating electrothermal flow in a rotating electric field (ROT-ETF), with primary attention paid to the horizontal traveling-wave electrothermal (TWET) vortex induced at the center of the electric field. The frequency-dependent flow profiles in the microdevice are analyzed using different heat transfer models. Accordingly, we address in particular the importance of electrode cooling in ROT-ETF as metal electrodes of high thermal conductivity while substrate material of low heat dissipation capability are employed to develop such microfluidic chips. Under this circumstance, cooling of electrode array due to external natural convection on millimeter-scale electrode pads for external wire connection occurs and makes the internal temperature maxima shift from the electrode plane to a bit of distance right above the cross-shaped interelectrode gaps, giving rise to reversal of flow rotation from a typical repulsion-type to attraction-type induction vortex, which is in good accordance with our experimental observations of co-field TWET streaming at frequencies on the order of reciprocal charge relaxation time of the bulk fluid. These results point out a way to make a correct interpretation of out-of-phase electrothermal streaming behavior, which holds great potential for handing high-conductivity analytes in modern microfluidic systems.

The concept of a Social License to Operate (SLO) has become increasingly important in the sustainability literature in recent years. Having its origins in the business discourse of the mining industry with respect to limiting opposition to mining projects, the notion of a social contract above and beyond legal requirements has since become applied across a number of different industries. Despite the concepts adoption confusion exists over the practices and outcomes of SLO, and particularly the nature of engagement. Given this situation it is surprising that not more attention to the role of marketing, and social marketing in particular, in operationalizing the concept. The paper discusses the potential of social marketing to contribute to SLO. Economic, political and social relations are complex in SLO and exchange is intricate in such relational environments. A community-based social marketing orientation is proposed as a means to improve exchange relations and enhance engagement. Seven models of SLO related social marketing models are discussed with community-based social marketing and adaptive co-marketing models being regarded as the most positive for the achievement of an SLO. Potential barriers to adoption of these approaches are noted.

Modular nanotransporters (MNTs) are drug delivery systems for targeted cancer treatment. Being composed of several modules, they offer the advantage of high specificity and biocompatibility in delivering drugs to the target compartment of cancer cells. The large carrier module brings together functioning MNT modules and serves as a platform for drug attachment. The development of smaller-sized MNTs via truncation of the carrier module looks advantageous in facilitating tissue penetration. In this study, two new MNTs with a truncated carrier module containing either an N-terminal (MNTN) or a C-terminal (MNTC) part were developed by genetic engineering. Both new MNTs demonstrated high affinity for target receptors, as revealed by fluorescently labeled ligand-competitive binding. The liposome leakage assay proved the endosomolytic activity of MNTs. Binding to the importin heterodimer of each truncated MNT was revealed by a thermophoresis assay, while only MNTN possessed binding to Keap1. Finally, the photodynamic efficacy of the photosensitizer attached to MNTN was significantly higher than when attached to either MNTC or the original MNT. Thus, this work reveals that MNT’s carrier module can be truncated without losing MNT functionality, favoring the N-terminal part of the carrier module due to its ability to bind Keap1.

In this study the distribution of heavy metal in the agricultural soils in the vicinity of 3 large mine-landfills around Kizhnica mine in Kosovo was investigated. The mining sector is one of the most important sectors of the economic development of Kosovo. The Kizhnica mine is one of the main ore producers in Kosovo. In addition to the positive aspects of production development it has its own side effects such as: industrial waste and the possibility of contamination of sur-rounding areas including the agricultural lands in the surrounding region. Ten sampling sites close to the Kizhnica mining complex were selected. These sampling sites have been characterized and evaluated as the most critical points, due to the anthropogenic influences of the discharge of industrial water from mining flotation and open tailing dumps in the Kizhnica. Concentration of Pb, Zn, Cu, As, Cd, Ni, Mn and Sb in selected samples was carried out by inductively coupled plasma–optical emission spectrometry (ICP–OES). Obtained data were used in order to generate geochemical maps and for calculatation the contamination factor (CF), pollution load index (PLI) and geo-accumulation index (Igeo). The statistical clustering analysis (CA), Pearson correlation coefficient (r) and air spatial distribution patterns using AERMOD View-Gaussian air dispersion model are used to perform evaluation within the area. The results demonstrated higher contents of the heavy metals in the vicinity of the mining area. It may be concluded that the heavy metal contents are impacted by anthropogenic nature of the contamination that confirms a current eco-logical threat of the mining activities in the region. Finally, a paper proposes the potential reas-signment of the deposed waste material into different combinations in construction in order to enhance the waste management and reduce the continued risk to: residents, lands and all living beings in the region.

Glutamate functions as the major excitatory neurotransmitter for primary sensory neurons and has a crucial role in sensitizing peripheral nociceptor terminals producing sensitization. Glutaminase (GLS) is the synthetic enzyme that converts glutamine to glutamate. GLS-immunoreactivity (-ir) and enzyme activity are elevated in dorsal root ganglion (DRG) neuronal cell bodies during chronic peripheral inflammation, but the mechanism for this GLS elevation is yet to be fully characterized. It has been well established that, after nerve growth factor (NGF) binds to its high-affinity receptor tropomyosin receptor kinase A (TrkA), a retrograde signaling endosome is formed. This endosome contains the late endosomal marker Rab7GTPase and is retrogradely transported via axons to the cell soma located in DRG. This complex is responsible for regulating the transcription of several critical nociceptive genes. Here, we show that this retrograde NGF signaling mediates the expression of GLS in DRG neurons during the process of peripheral inflammation. We disrupted the normal NGF/TrkA signaling in adjuvant-induced arthritic (AIA) Sprague Dawley rats by pharmacological inhibition of TrkA or blockade of Rab7GTPase, which significantly attenuated the expression of GLS in DRG cell bodies. These results indicate that NGF/TrkA signaling is crucial for the production of glutamate and has a vital role in the development of neurogenic inflammation. In addition, our pain behavioural data suggest that Rab7GTPase can be a potential target for attenuating peripheral inflammatory pain.

Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s^-1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s-1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modelling informed by biology can provide new pathphysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.

As a key mediator of chronic pain, neurotrophin nerve growth factor (NGF) binds to two neurotrophin receptors: p75 neurotrophin receptor (p75NTR) and tyrosine kinase receptor A (TrkA). The formation of the p75NTR-NGF-TrkA complex is implicated in the potentiation of chronic pain signals, making it an attractive target for therapeutic explorations. NGF analogues and monoclonal antibodies (mAbs) targeting NGF represent two distinct approaches in modulating the intricate signaling pathways involved in pain transduction mediated by the p75NTR-NGF-TrkA complex. While NGF analogues offer the advantage of tailored design to fine-tune neurotrophic responses, monoclonal antibodies provide a more systemic and comprehensive blockade of NGF, inhibiting its interactions with both p75NTR and TrkA receptors. However, the use of mAbs may pose challenges related to potential side effects and interference with the physiological functions of NGF. As a result, balancing the benefits and drawbacks of the two approaches is critical for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain. In this study, therefore, a novel structural and biophysical approach was employed for the design of NGF analogues to suppress p75NTR-NGF-TrkA-related chronic pain signaling. Employing high-throughput structural modeling and biophysics-based intermolecular binding affinity calculations, this article for the first time puts forward a set of NGF analogues, including in particular NGF analogues with four site-specific mutations, for whose dimerizations the K d at 37 ^◦C were reduced by three orders of magnitude (from 10^-9 M to 10^-6 M) compared to the K d at 37 ^◦C for the dimerization of native NGFs. Overall, the integration of structural and biophysical perspectives enhances our understanding of the rational design of NGF analogues as promising candidates for the development of NGF-targeted analgesic therapies, which balances the benefits and drawbacks of anti-NGF antibodies and NGF analogues for advancing therapeutic strategies towards the alleviation of p75NTR-NGF-TrkA-mediated pain.

This paper presents a new implementation of a 2-box absolute flow model, enabling the calculation of CO₂ transfer between the atmosphere and a mixing reservoir representing the combined effect of the terrestrial and ocean regions. The model uses published values of anthropogenic CO₂ fossil fuel emissions (CO2ff), atmospheric CO₂ mixing ratio and nuclear weapons bomb yields, to compute atmospheric d¹³C and Δ¹⁴C time-series. The level of agreement between the calculated values and the accepted values for d¹³C is within ± 0.05 ‰, and for Δ¹⁴C is within ± 3‰, spanning 200 years. The model contains only seven internal parameters; these are varied to optimize the fit, leading to reasonable parameter values, indicating the validity of the method. In addition, the model shows how a rising CO₂ exchange influx fluctuating with surface temperature is compatible with a nett atmospheric CO₂ sink. The study demonstrates that a single CO₂ residence time applies to both the ¹⁴C bomb pulse and the anthropogenic flux, contrary to the conventional view that "bomb radiocarbon and anthropogenic CO₂ do not behave identically." [Joos 1994 Nature 370, 181–182]. It is shown that the difference in behaviour, claimed to be due to seawater chemistry, is not significant in practice since fluctuating bulk carbon dominates fluctuating isotopic ratio. A new analysis of the airborne fraction indicates that the assumption of a time-dependent exchange influx results in a similar residence time for bulk CO₂ as for ¹⁴C in the nuclear bomb pulse, reinforcing the view that the ¹²C, ¹³C and ¹⁴C carbon isotopic forms of CO₂ behave similarly in the carbon cycle.

Solventogenic Clostridium species are important for establishing sustainable industrial bioproduction of fuels and important chemicals. The inherent versatility of these species in substrate utilization and the range of solvents produced during acetone butanol-ethanol (ABE) fermentation make solventogenic Clostridium an attractive choice for biotechnological applications such as production of fuels and chemicals. The functional qualities of these microbes have thus been identified to be due to complex regulatory networks that play essential roles in modulating the metabolism of this group of bacteria. Genomes of solventogenic Clostridium species have relatively greater prevalence of genes that are intricately controlled by various regulatory molecules than most other species. Consequently, the use of genetic or metabolic engineering strategies that do not consider the underlying regulatory mechanisms will not be effective. Several regulatory factors involved in substrate uptake/utilization, sporulation, solvent production, and stress responses (Carbon Catabolite Protein A, Spo0A, AbrB, Rex, CsrA) have been identified and characterized. In this review, the focus is on newly identified regulatory factors in solventogenic Clostridium species, the interaction of these factors with previously identified molecules, and potential implications on substrate utilization, solvent production, and resistance/tolerance to lignocellulose-derived microbial inhibitory compounds.

Hypoxia can induce pulmonary edema (PE) and inflammation. Furthermore, hypoxia depresses left ventricular (LV) inotropy despite sympathetic activation. Here, we investigated the role of nitrosative stress and cardiovascular dysfunction in hypoxic lung injury. Additionally, we studied effects of adrenergic blockade (AB) on hypoxia-induced pulmonary injury. Eighty-six female rats were exposed for 72 h to normoxia or normobaric hypoxia and received infusions with NaCl, prazosin, propranolol or prazosin-propranolol combination. We evaluated hemodynamic function and performed histological and immunohistochemical analyses of the lung. Hypoxia significantly depressed LV but not right ventricular (RV) inotropic and lusitropic functions. AB significantly decreased LV function both in normoxia and hypoxia. AB effects on RV were weaker. Hypoxic rats showed signs of moderate PE and inflammation. This was accompanied by elevated levels of tumor necrosis factor (TNF)  and nitrotyrosine, a marker of nitrosative stress in the lungs. In hypoxia, all types of AB significantly reduced both TNF and nitrotyrosine to normoxic levels. However, AB did not attenuate PE. Results suggest that hypoxia-induced sympathetic activation contributes to inflammation and nitrosative stress in the lungs but not to PE. We suggest that AB in hypoxia aggravates hypoxia-induced inotropic LV dysfunction and backlog into pulmonary circulation, thus promoting PE.

Abstract Background: Cluster randomized controlled trials are increasingly becoming popular in public health research interventions and health services research in primary health care design and use in low and middle-income countries. However, the majority of researchers in these trials did not account correctly for the effect of confounders and clustering in the design and analysis stages. Objectives: This article aimed to review the main implications of implementing a cluster randomized controlled trials design in public health research and emphasize the practical application of proper analytical methods and the performance of different statistical models. Methods: The practical application of various analytical methods is validated via the utilization of experimental data from a public health research case study. This article also demonstrated the performance of hierarchical models and made comparisons in terms of empirically precise effect size estimates. Results: Three hierarchical statistical models were provided with highly varied effect sizes during the analysis of the intervention effect on outcome, such as model 1 (AOR: 14.32; 95% CI: 3.75–54.68), model 2 (ARR: 3.52; 95% CI: 2.16–5.77), and model 3 (ARR: 4.79; 95% CI: 2.69–5.52).Conclusion: Inaccurate results and potentially misleading conclusions can arise from improper cluster randomized controlled trial designs and analyses. This article has shown that real-world data can be adjusted for the effects of confounders and clustering, and we advocate for the routine use of suitable design and analytical methods. This article concludes that researchers should be careful when selecting hierarchical models to analyze cluster randomized controlled trials.

Perilla frutense var. acuta (Lamiaceae) has been used to treat indigestion, asthma, and allergies in traditional medicine. In this study, luteolin 7-O-diglucuronide (1), apigenin 7-O-diglucuronide (2), and rosmarinic acid (3) were isolated from the leaves of P. frutescens var. acuta. Various approaches were performed to investigate the anti-inflammatory activity of the isolated compounds (1-3) and their working mechanisms. In silico docking simulation demonstrated that 1-3 would work as a PPAR-α/δ/γ agonist, and in vitro PPAR-α/δ/γ transcriptional assay showed that the Perilla extract and 3 increased PPAR-α luciferase activity [1.71 and 1.61 times of the control (PPAR-α + PPRE, p < 0.001)]. In the NF-κB luciferase assay, 1 suppressed NF-κB activity the most (56.83 % at 5 µM; 74.96 % at 10 µM; 79.86 % at 50 µM). In addition, 1 and 2 inhibited the mRNA expression of NF-κB target genes, including Il6, Mcp1, and Tnfa, at 50 µM, and 3 suppressed the genes at the mRNA level in a dose-dependent manner. We report that 1 and 2 exert anti-inflammatory effects through NF-κB inhibition, and PPAR-α/NF-κB signaling pathway is related to the anti-inflammatory activity of 3.

This study is based on the fatty acid and amino acid profile of 7 edible insect species: Acheta domesticus, Alphitobius diaperinus, Blaptica dubia, Galleria mellonella, Locusta migratoria, Tenebrio molitor and Zophobas morio. The fatty acid distribution within lipid classes (neutral lipids, glycolipids and phospholipids) was studied, while the amino acid profile was used to calculate the species-specific nitrogen-protein conversion factor (Kp). The profiles were used to evaluate the nutritional quality of the lipids and proteins. Oleic acid was the predominant fatty acid in all insects except for A. domesticus, in which a larger percentage of linoleic acid was found. The majority of the lipids were neutral lipids. L. migratoria showed a remarkably high content of α-linolenic acid in its phospholipid fraction, while T. molitor phospholipids were the only fraction in which a measurable amount of docosahexaenoic acid was found. Overall, in most insects, the phospholipid fraction had the highest polyunsaturated fatty acid content compared to the other classes, which may be protective in terms of autoxidative stability. Kp values in the range of 4.17 to 6.43 were obtained. Within the nutritional quality indices, all insects showed healthy fatty acid and high quality amino acid profiles.

Glioblastoma (GBM) is a representative malignant brain tumor characterized by a dismal prognosis, with survival rates of less than 2 years and high recurrence rates. Despite surgical resection and several alternative treatments, GBM remains a refractory disease due to its aggressive invasiveness and resistance to anticancer therapy. In this report, we explore the role of fibronectin type III domain containing 3B (FNDC3B) and its potential as a prognostic and therapeutic biomarker in GBM. GBM exhibited a significantly higher cancer-to-normal ratio compared to other organs, and patients with high FNDC3B expression had a poor prognosis (p < 0.01). In vitro studies revealed that silencing FNDC3B significantly reduced the expression of Survivin, an apoptosis inhibitor, and also reduced cell migration, invasion, extracellular matrix adhesion ability, and stem cell properties in GBM cells. Furthermore, we identified that FNDC3B regulates PTEN/PI3K/Akt signaling in GBM cells using MetaCore integrated pathway bioinformatics analysis and a proteome profiler phospho-kinase array with sequential western blot analysis. Collectively, our findings suggest FNDC3B as a potential biomarker for predicting GBM patient survival and for the development of treatment strategies for GBM.

Long span cable-stayed bridge is the main bridge type with a span of more than 400 meters. It is generally designed as a double tower long-span structure with good spanning capacity and economic performance. Wind resistance safety performance is the main index to control the long-span cable-stayed bridge structure. During the operation of long-span cable-stayed bridge structure, because the service life of the cable is far less than the design life of the structure, the wind resistance performance of the structure will inevitably deteriorate significantly, which will seriously affect the structural service performance of symmetric cable-stayed bridge. Based on symmetric reliability theory, this paper takes flutter and static wind stability of long-span cable-stayed bridge structure as the main design control index, uses positive reliability theory to calculate the reliability index of symmetric cable-stayed bridge structure, uses inverse reliability theory to calculate the safety factor of symmetric cable-stayed bridge structure, and evaluates the wind resistant time-varying performance of long-span cable-stayed bridge structure by comprehensively considering the reliability index and safety factor. Taking a practical project of a long-span cable-stayed bridge as a specific case, the wind resistant time-varying reliability of the bridge during its operation for more than 30 years is analyzed, and the parameter sensitivity is analyzed. The results show that the wind resistance performance of the cable-stayed bridge structure is obviously affected by the cable, and the degradation of the cable performance will have an important impact on the wind resistance time-varying performance of the structure, especially the critical wind speed of the structure has obvious time-varying characteristics. The safety factor and reliability index can objectively evaluate the wind resistance time-varying performance of the long-span cable-stayed bridge structure.

The Apetala2/ethylene response factor superfamily refers to a group of transcription factors that share a conserved AP2 DNA binding domain. These factors have been found to have different roles in plant responses to both biotic and abiotic stresses. Samples of hexaploid wheat, tetraploid pasta (or durum wheat), and diploid wheat progenitors were selected. The 29 dehydration-responsive element binding transcription factors in these samples were downloaded from NCBI GenBank for six different countries: Iran, China, Italy, France, Afghanistan, and Azerbaijan. The AP2 domain sequences were identified from the dehydration-responsive element binding transcription factors using PROSITE, ProDom, and SMART software. Next, all sequences were aligned using Multalin and Jalview software. The aligned sequences were then analyzed to identify amino acid locations, types, and frequencies. The multiple alignments showed that approximately 76% of the amino acid residues in the AP2 domains are conserved. According to the amino acid analysis, alanine, serine, and glutamic acid are the most abundant amino acids found in three motifs. The performed phylogenetic analysis illustrates the role of geographical effects on the transcription factor sequences of bread wheat in the Middle East. Significant differences were found between Iranian and Chinese transcription factor sequences. Moreover, genetic variation was observed in the transcription factors of Italian sequences found in pasta and wheat progenitors. Motif structures play a critical role in the domain organization of wheat proteins to enhance the characteristics of assorted metabolic pathways. The structure of the AP2 domain was analyzed by several programs, I-TASSER for instance, to identify the α-helix, β-sheets, and the regions of some significant amino acids in the 3-D model.

Lead-based ternary chalcogenide thin films of the (PbTe)1-x(PbS)x system were obtained by plasma-enhanced chemical vapor deposition technique (PECVD) under conditions of a nonequilibrium low-temperature argon plasma of an RF discharge (40.68 MHz) at a reduced pressure (0.01 Torr). High-purity elements were directly used as starting materials – Pb, S and Te. Plasma-chemical synthesis was carried out on the surface of of c-sapphire and silicon substrate. The physicochemical properties of the films were studied by various analytical methods. The dependence of the Seebeck coefficient, resistivity, and power factor on the structural properties and composition has been studied. The thermoelectric characteristics were found to be dependent on the film composition. Upon the selection of optimal sulfur concentration one can increase the power factor as compared to single phase PbS ot PbTe films.

Breast cancer represents the most frequent cancer and the leading cause of cancer death among women. Thus, the prevention and early diagnosis of breast cancer appears to be of primary urgency as well as the development of new treatments able to improve its prognosis. Nerve Growth Factor (NGF) is a neurotrophic factor that plays a key role in the regulation of neuronal functions thought the binding to the Tropomyosin receptor kinase A (TrkA) and the Nerve Growth Factor receptor or Pan-Neurotrophin Receptor 75 (NGFR/p75NTR). Also, its precursor (pro-NGF) can extert biological activity by forming a trimeric complex with NGFR/p75NTR and sortilin or by binding to TrkA receptors with low affinity. Both in vitro and in vivo studies showed that NGF is synthesized and released by breast cancer cells and has mitogen, antiapoptotic and angiogenic effects on these cells through the activation of different signaling cascades that involve TrkA and NGFR/p75NTR receptors. Conversely, pro-NGF signaling has been related to breast cancer invasion and metastasis. Other studies suggested that NGF and its receptors could represent a good diagnostic and prognostic tool, as well as promising therapeutic targets for breast cancer. Here, we comprehensively summarize and systematically review the current experimental evidence on this topic.

In this work, we examine the deflection angle of black hole in effective loop quantum gravity in non-plasma medium via the geometrical technique of Gibbons and Werner in weak field limits. For this, we attain the optical metric and calculate the Gaussian optical curvature and then we apply the Gauss-Bonnet theorem. We also study the influence of the plasma and dark matter mediums on the deflection angle. Further, we obtain the deflection angle by using Keeton and Petters method. We also calculate the Hawking temperature via Gauss-Bonnet theorem. In addition, we determine the fermionic greybody bounds. Moreover, we discuss the graphical behaviour of the bending angle and bounds on the greybody factor. We also examine that the results obtained for the black hole in effective loop quantum gravity are reduces to the Schwarzschild black hole solutions when dimensionless non-negative parameter $A_{\lambda}=0$.

Tick-borne encephalitis virus (TBEV) is a pathogenic, enveloped, positive-stranded RNA virus in the family Flaviviridae. Structural studies of flavivirus virions have primarily focused on mosquito-borne species with only one cryo-electron microscopy (cryo-EM) structure of a tick-borne species published. Here, we present a 3.3 Å cryo-EM structure of the TBEV virion of the Kuutsalo-14 isolate, confirming the overall organisation of the virus. We observe conformational switching of the peripheral and transmembrane helices of M protein, which can explain the quasi-equivalent packing of the viral proteins and highlights their importance in stabilizing the membrane protein arrangement in the virion. The residues responsible for the M protein inter-actions are highly conserved in TBEV but not in the structurally studied Hypr strain, nor in mosquito-borne flaviviruses. These interactions may compensate for the lower number of hydrogen bonds between E proteins in TBEV compared to the mosquito-borne flaviviruses. The structure reveals two lipids bound in the E protein, which are important for virus assembly. The lipid pockets are comparable to those recently described in mosquito-borne Zika, Spondweni, Dengue, and Usutu viruses. Our results thus advance the understanding of tick-borne flavivirus architecture and virion-stabilising interactions.

The Short-Term Assessment of Risk and Treatability (START) is deemed the most appropriate instrument for assessing violence risks and management because of its balanced approach between dynamic risk and protective factors. Although several facets of reliability and predictive validity of this tool were strong, its inter-rater reliability, construct validity, and implementation in Asian population were under-investigated. The objective of this research was to examine the inter-rater reliability and construct validity of the START: Thai version within forensic psychiatric inpatients. The participants consisted of 118 forensic psychiatric inpatients hospitalized at Galya Rajanagarindra Institute in Thailand. Trained mental health professionals (i.e., psychiatrists, forensic nurses, clinical psychologists, social workers, and occupational therapists) assessed each participant across twenty domains of the Thai START. The inter-rater reliability was examined using the intraclass correlation coefficient and a confirmatory factor analysis for ordinal data was used to test the construct validity of the scale. The main finding showed a good-to-excellent inter-rater reliability and supported two relational constructs (i.e., strength vs vulnerability subscales) of the Thai START. The Thai START is a promising tool for using in Thai forensic psychiatric setting but some items were not significant in contributing to the scale. This study also provides the guideline for implementing the tool in non-Western forensic psychiatric populations.

Approximately 240 million people are chronically infected with hepatitis B virus (HBV), despite four decades of an effective HBV vaccine. During chronic infection, HBV forms two distinct templates responsible for viral gene transcription: (1) episomal covalently closed circular (ccc)DNA and (2) host-genome integrated viral templates. Multiple ubiquitous and liver-specific transcription factors are recruited onto these templates and modulate viral gene transcription. This review details the latest developments in antivirals that inhibit HBV gene transcription, and their impact on the stability of viral transcripts. Notably, nuclear receptor agonists exhibit potent inhibition of viral gene transcription from cccDNA, small molecule inhibitors repress HBV X protein-mediated transcription from cccDNA and small interfering RNAs and single-stranded oligonucleotides result in transcript degradation from both cccDNA and integrant templates. These antivirals mediate their effects by reducing viral transcripts abundance, eventually leading to loss of surface antigen expression, and can potentially be added to the arsenal of drugs with demonstrable anti-HBV activity. Thus, these candidates deserve special attention for future repurposing or further development as anti-HBV therapeutics.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

The structure of self-reinforced composites (SRCs) based on ultra-high molecular weight 21 polyethylene (UHMWPE) was studied by means of Wide-Angle X-Ray Scattering (WAXS), X-Ray 22 tomography, Raman spectroscopy, Scanning Electron Microscopy (SEM) and in situ tensile testing 23 in combination with advanced processing tools like Avizo, ImageJ, and Ncorr to determine the cor-24 relation between the processing conditions, on the one hand, and the molecular structure and 25 mechanical properties, on the other. SRCs were fabricated by hot compaction of UHMWPE fibers at 26 different pressure and temperature combinations without addition of polymer matrix or softener. 27 It was found by WAXS that higher compaction temperatures led to more extensive melting of 28 fibers with the corresponding reduction of the Herman’s factor reflecting the degree of molecular 29 orientation, while the increase of hot compaction pressure suppressed the melting of fibers within 30 SRCs at a given temperature. X-Ray tomography proved the absence of porosity while polarized 31 light Raman spectroscopy measurements for both longitudinal and perpendicular fiber orienta-32 tions showed qualitatively the anisotropy of SRC samples. SEM revealed that the matrix was 33 formed by interlayers of molten polymer entrapped between fibers in SRCs. Moreover, in situ 34 tensile tests demonstrated the increase of Young’s modulus and tensile strength with increasing 35 temperature.

Penicillium digitatum is the major postharvest pathogen of citrus fruit under Mediterranean climate conditions. In the present work, we have addressed the study of the role of P. digitatum’s proteases in virulence following two complementary approaches. In a first approach, we have undertaken the functional characterization of the P. digitatum prtT gene, which codes for a transcription factor previously shown to regulate extracellular proteases in other filamentous fungi. Deletion of prtT caused a significant loss in secreted protease activity during in vitro growth assays. However, there was no effect on virulence. Gene expression of the two major secreted acid proteases was barely affected in the ΔprtT deletant during infection of citrus fruit. Hence, no conclusion could be drawn on the role of these secreted acidic proteases on the virulence of P. digitatum. In a second approach, we have studied the effect of different protease inhibitors and chelators in virulence. Co-inoculation of citrus fruit with P. digitatum conidia and a cocktail of protease inhibitors resulted in almost a complete absence of disease development. Analysis of individual inhibitors revealed that the metalloprotease inhibitor 1,10-phenanthroline was responsible for the observed effect. The application of metal ions reverted the protective effect caused by the metallopeptidase inhibitor. These results may set the basis for the development of new alternative treatments to combat this important postharvest pathogen.

A Natural gas is increasingly being sought after as a vital source of energy, given that its production is very cheap and does not cause the same environmental harms that other resources, such as coal combustion, do. Understanding and characterizing the behavior of natural gas is essential in hydrocarbon reservoir engineering, natural gas transport, and process. Natural gas compressibility factor, as a critical parameter, defines the compression and expansion characteristics of natural gas under different conditions. In this study, a simple second-order polynomial model based on the group method of data handling (GMDH) is presented to determine the compressibility factor of different natural gases at different conditions, using corresponding state principles. The accuracy of the model evaluated through graphical and statistical analyses. The results show that the model is capable of predicting natural gas compressibility with an average absolute error of only 2.88%, a root means square of 0.03, and a regression coefficient of 0.92. The performance of the developed model compared to widely known, previously published equations of state (EOSs) and correlations, and the precision of the results demonstrates its superiority over all other correlations and EOSs.

Due to the upward trend in the globalization of sustainability issues and the intense competitive environment, it is evident that higher education institutions need new strategic approaches to succeed. To this end, the inquiry for this paper has been made into the debate about student relationship management. Going through the literature indicates that institutions have mainly perceived the concept as a technological initiative for solving the problems in individual domains, accompanied by uncoordinated efforts. Thus, the aims of this study are to theoretically present critical success factors of this strategic approach and to empirically examine the recognized factors. To do so, confirmatory factor analysis that is a quantitative analytic method was performed. The results and analyses revealed that there has been a significant correlation between the four critical success factors including knowledge management, student relationship management technology, student orientation, and employees’ involvement. It was also found that these factors are significantly correlated with the construct of student relationship management success. The findings have consequently highlighted that in addition to the technological tool, the role of knowledge management, employees’ involvement, and student orientation appeared to be particularly important for the implementation of the application.

Referring to the concept of inclusive growth, the authors analyse the transition economies of the Central and Eastern European countries, which are the current EU members (Bulgaria, Croatia, the Czech Republic, Estonia, Latvia, Lithuania, Hungary, Poland, Romania, Slovakia and Slovenia). That region was selected as the CEE countries characterized by comparable historic and economic background but now they seem to reach diversified stages of development. The objective of the study is to identify the level of inclusive growth among the CEE countries, taking into account indicators assigned to its seven pillars. The thesis is that the CEE countries represent socio and economic heterogeneity as well as different levels of sustainable development. The research methods involved the application of the principal components analysis and the multivariate analysis. For literature review, the bibliometric analysis was conducted with the visualization prepared by the VOSviewer software. The main findings suggest that Estonia, Slovenia and the Czech Republic seem to be the ones with the highest inclusive growth. On the other hand, Bulgaria and Romania represent the lowest level of inclusive growth indicators.

The key to simulating soil erosion is to calculate the vegetation cover (C) factor. Methods that apply remote sensing to calculate C factor at regional scale cannot directly use the C factor formula. That is because the C factor formula is obtained by experiment, and needs the coverage ratio data of croplands, woodlands and grasslands at standard plot scale. In this paper, we present a C factor conversion method from a standard plot to a km-sized grid based on large sample theory and multi-scale remote sensing. Results show that: 1) Compared with the existing C factor formula, our method is based on the coverage ratio of croplands, woodlands and grasslands on a km-sized grid, takes the C factor formula obtained from the standard plot experiment and applies it to regional scale. This method improves the applicability of the C factor formula, and can satisfy the need to simulate soil erosion in large areas. 2) The vegetation coverage obtained by remote sensing interpretation is significantly consistent (paired samples t-test, t = −0.03, df = 0.12, 2-tail significance p < 0.05) and significantly correlated with the measured vegetation coverage. 3) The C factor of the study area is smaller in the middle, southern and northern regions, and larger in the eastern and western regions. The main reason for that is the distribution of woodlands, the Hunshandake and Horqin sandy lands and the valleys affected by human activities. 4) The method presented in this paper is more meticulous than the C factor method based on the vegetation index, improves the applicability of the C factor formula, and can be used to simulate soil erosion on large scale and provide strong support for regional soil and water conservation planning.

Thirteen benzylethylenearyl ureas and one carbamate have been designed, synthesized and biologically evaluated as regards their antiproliferative activity on tumor cell lines HEK-293 and A-549 and on the immune and endothelial Jurkat T cells and HMEC-1, respectively. A relationship between the structure of the synthetic compounds and their antiproliferative activity has been established. Compounds C.1, C.3, C.12 and C.14 were chosen for further biological studies in order to determine their potential as oncoimmunomodulating agents. Some compounds exhibited significant inhibitory effects on both total PD-L1 and VEGFR-2 in HT-29 cell line, showing urea C.12 active against both targets. Some compounds could reduce more than 50% of cancer living cells, compared to non-treated ones, when assessed in co-cultures using HT-29 and THP-1 cells. In addition, these compounds showed no effect on the immune cell viability and significantly reduce CD11b expression, which is a promising target for immune modulation in anti-cancer therapies.

Using of the organic base tetramethylammonium hydroxides (TMAH) is a viable, cheap and fast route, for the MgZnAl-LDH type materials synthesis by both co-precipitation and mechano-chemical methods. TMAH provided several advantages as smaller quantity of water required in the washing step compared to the use of inorganic alkalis, prevention of LDH contamination with alkali cations, acting as template molecule in texture tailoring along with disadvantages as its presence in small quantities in the resulting layered materials. Regardless the use of organic / inorganic bases and co-precipitation / mechano-chemical methods, zincite stable phase was found in all the synthesized solids. The basicity of catalysts followed the trend: mixed oxides &gt; reconstructed &gt; parent LDH. The memory effect of LDH is supported only by the presence of Mg and Al cations, while Zn remains as zincite stable phase. The catalytic activities for Claisen-Schmidt condensation of benzaldehyde with cyclohexanone provided values higher than 90% after 2h, with a total selectivity in 2,6-dibenzylidenecyclohexanone, while in self-condensation of cyclohexanone no more than 7.29% after 5h. These behaviors depended on catalysts basicity as well as the planar rigidity of the compound.

Selection of co-belonging fragments from the numerous ceramic findings of an archaeological excavation remains a difficult process of questionable effectiveness, based exclusively on the experience and patience of the conservators. While the screening of the fragments is a central prerequisite and the most important stage of the process of vase reconstruction, established methods based on scientific criteria and guaranteed efficiency for the detection of co-belonging ceramic fragments suggested in the bibliography, do not exist. On the contrary, for methods dealing with the assembly of vases from co-belonging fragments, which is a secondary process that can be done more easily and effectively in an empirical way, there exist numerous studies based on fragment morphology. However, even these are also not implemented because of the time requirements, sheer volume and complexity of the proposed methods, in order for them to be applicable in practice. The proposed methods in this paper are based on thermoremanent magnetization (A/m), which is calculated from the weak magnetic field measurements by a fluxgate-sensor/magnet apparatus forming a three-dimensional orthogonal system. Experimental measurements from fragments of 6 vases show that the magnetization magnitude of co-belonging fragments display similar values, despite the magnetic anisotropy of the ceramic material, since these belong to vases that are made of the same clay and fired under the same conditions. This is the criterion for finding ceramic fragments of the same vase from archaeological excavations. The thermoremanent magnetism directionality of fragments, which is aligned along the geomagnetic field at the same place and time during the vase firing process, as it is configured by their rotational symmetry, defines the position of the fragments on the body of the 6 vases. The shape of the original vase can be reconstructed when only a few non adjacent fragments are available. The proposed measurement apparatus can be used for the construction of a useable portable magnetometer specialized for ceramic surface measurements to achieve the above objectives.

The purpose of this study is nutrient resources recovery by achieving the optimal chemical oxygen demand (COD) and carbon to nitrogen ratio (C/N) in co-composting wastewater treatment plant sludge with Municipal Solid Wastes (MSW). In this effort, the co-composting has been conducted in form of a case study in the northern region of Iran. In this research, 192 tests were carried out on four series of samples examined in terms of waste to sludge ratio, different aeration period, the percent of porous materials and the moisture content. This study was carried out at a temperature of 50 °C for a 15 day period by application of the in-vessel system and shows that the best ratio for waste to sludge is 2:1, while the 8 hour period is the best aeration period. The porous material which can be added to the composting process is limited to 15% in weight. In other words, any more or less amount of this material will adversely impact the process. Moreover, this research suggests that the sludge dewatering is not required in such processes. In Addition, the efficiency of both COD and C/N reductions equals to about 40%.

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that anti-proliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a co-culture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to monoculture. Notably, pseudopterosin proved to block cytokine elevation, representing key players in tumor progression, in the co-culture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy.

Abstract: We review the development and application of an organic polymer-gel capable of producing fixed, three-dimensional fluorescent images of complex radiation fields. The gel consists for more than 99% of γ-ray-polymerized (~15% conversion) tertiary-butyl acrylate (TBA) containing ~100 ppm of a fluorogenic compound, e.g. maleimido-pyrene (MPy). The radio-fluorogenic effect depends on copolymerization of the MPy into growing chains of TBA on radiation-induced polymerization. This converts the maleimido residue, which quenches the pyrene fluorescence, into a succinimido moeity (SPy), which doesn't. The intensity of the fluorescence is proportional to the yield of free-radicals formed and hence to the local dose deposited. Because the SPy moieties are built into the cross-linked polymer matrix the image is fixed. The method of preparing the gel and imaging the radiation-induced fluorescence are presented and discussed. The effect is illustrated with fluorescent images of the energy deposited in the gel by beams of X-rays, electrons and protons as well as a radioactive isotope.

In this paper, the performance of Cu-(In,Ga)-S2 (CIGS2) solar cells with adjusting composite CGI-ratio absorber is explored and compared through an improved three-stage co-evaporation technique. For co-evaporating CIGS2 absorber as a less toxic alternative to Cd-containing film, we analyse the effect of the CGI-ratio stoichiometry and crystallinity, and explore its opto-electric sensing characteristic of individual solar cell. The results of this research signify the potential of high-performance CIGS2-absorption solar cells for photovoltaic (PV)-module industrial applications. For the optimal CIGS2-absorption film (CGI=0.95), the Raman main-phase signal (A1) falls at 291 cm-1, which is excited by the 532-nm line of Ar+-laser. Using photo-luminescence (PL) spectroscopy, the corresponding main-peak bandgaps measured is 1.59 eV at the same CGI-ratio film. Meanwhile, the best conversion efficiency (=3.212%) and the average external quantum efficiency (EQE=51.1% in the visible-wavelength region) of photo-electric properties were achieved for the developed CIGS2-solar cells (CGI=0.95). The discoveries of this CIGS2-absorption PV research provide a new scientific understanding of solar cells. Moreover, this research undeniably contributes to a major advancement towards practical PV-module applications and can help more to build an eco-friendly community.

Ghana, blessed with abundant solar resources and has strategically invested in solar photovoltaic (PV) technologies to diversify its energy mix and reduce the environmental impacts of traditional energy technologies. The 50 MW solar PV installation by the Bui Power Authority exemplifies the nation's dedication to utilizing clean energy for sustainable growth. This study seeks to close the knowledge gap by providing a detailed analysis of the system's performance under different weather conditions, particularly on days with abundant sunshine and those with cloudy skies. The research consists of one-year monitoring data of the climatic and AC energy output fed into the grid. This data was used to analyze PV performance on each month's sunniest and cloudiest days. The results show that the total amount of AC energy output fed into the grid each month on the sunniest day varies between 229.3 MWh in December and 278.0 MWh in November, while the total amount of AC energy output fed into the grid each month on the cloudiest day varies between16.1 MWh in August and 192.8 MWh in February. Also, the percentage variation in energy produced between the sunniest and cloudiest days within a month ranges from 16.9% (December) to 94.1% (August). The reference and system yield analysis showed that the PV plant has a high conversion efficiency of 91.3%; however, only the sunniest and overcast days had an efficiency of 38% and 92%, respectively. The BPA plant's performance can be enhanced by using this analysis to identify erratic power generation on sunny days and schedule timely maintenance to keep the plant's performance from deteriorating. Optimizing a solar PV system's design, installation, and operation can significantly improve its AC energy output, performance ratio, and capacity factor on sunny and cloudy days.

Many anti-tumor effects of group-specific component-derived macrophage-activating factors (GcMAFs) have been reported; however, the specific mechanisms remain unclear. Controlling tumor-associated macrophages (TAMs) in the tumor microenvironment is essential for cancer treatment. This study assessed the role of GcMAF in macrophage activation, elucidated the mechanisms by which it exerts its anti-tumor effects, and determined its effects on TAMs in the tumor microenvironment. GcMAF-stimulated RAW264.7 macrophages and EMT6 breast tumor cells were co-cultured in a 0.4-µm pore cell culture insert, and gene and protein expression and cell viability were evaluated. DNA microarray analysis of GcMAF-stimulated RAW264.7 cells was conducted. The induction of M2 RAW264.7 cells by interleukin (IL)-4 and IL-13 was analyzed. GcMAF stimulation increased the tumor necrosis factor-α and inducible nitric oxide synthase mRNA and protein levels in RAW264.7 cells but decreased the viability of co-cultured EMT6 cells. These results were confirmed in the M2 RAW264M2.7 cells, suggesting that GcMAF exerts anti-tumor effects by inducing the differentiation of macrophages into the M1 type and reprogramming M2 macrophages to the M1 type. The anti-tumor activity of GcMAF via M2-to-M1 macrophage reprogramming could aid in developing novel cancer immunotherapies.

Keywords: retinoblastoma, RB, gastric inhibitory polypeptide receptor, GIPR, trefoil factor family peptide, TFF1, CAM, tumorigenesis, MK0893, miR5-542-5p

We presented a fractional order model to capture the transmission dynamics of Anthrax infection with a nonlinear force of infection and its long-term impacts. Analysis by the standard Fabrizio Caputo approach established the model is well-posed and investigation on the stability of the model, Anthrax-free equilibrium as connected to the basic reproduction number R0

This study determines the equivalent stress intensity factor (SIF) model that best fits the experimental behavior of low-carbon steel under mixed mode (I and II). The study assessed Tanaka, Richard, and Pook's equivalent SIF models. The theoretical values used for comparison correspond to experimental results in a modified C(T) geometry by machining a hole ahead of the crack tip subjected to fatigue loads with a load ratio of R = 0.1. The comparison involved the SIF for six experimental points and the values computed through the numerical simulation. The Paris, Klesnil, and modified Forman-Newman crack growth models were used with each equivalent SIF to analyze the prediction in the estimated number of cycles. The Klesnil model showed the closest prediction since the error between the calculated and experimentally recorded number of cycles is the lowest. However, the material behavior reflects a reduced crack propagation rate attributed to plasticity in the crack tip. Results suggest that Asaro equivalent SIF conservatively estimates the element lifespan with increasing errors from 2.3% at the start of growth to 27 % at the end of the calculation.

The homeostasis of cellular calcium is fundamental for many physiological activities, while calcium levels maintain inhomogeneous within cells. During the onset of asthma, epithelial and inflammatory cells secrete platelet derived growth factor (PDGF), inducing proliferation and migration of airway smooth muscle (ASM) to the epidermal layer, narrowing the airway. The regulation of ASM cells by PDGF is closely related to the conduction of calcium signals. In this work, we generated subcellular-targeted FRET biosensors to investigate calcium regulations at different compartments of ASM cells. PDGF-induced cytoplasmic calcium [Ca2+]C increase was attributed from both extracellular calcium influx and endoplasmic reticulum (ER) calcium [Ca2+]ER release, which was partially regulated by PLC-IP3R pathway. Interestingly, removal of extracellular calcium influx led to inhibited ER calcium release, likely through inhibitory effect on calcium-dependent activation of ER ryanodine receptor. Inhibition of L-type calcium channel on plasma membrane, or SERCA pump on ER resulted in both reduced [Ca2+]C and [Ca2+]ER from PDGF stimulation, while IP3R channel inhibition led to reduced [Ca2+]C only. Inhibited SERCA pump caused immediate [Ca2+]C increase and [Ca2+]ER decrease, indicating an active calcium exchange between cytosol and ER storage in resting cells. PDGF-induced calcium at outer mitochondrial membrane sub-region showed similar regulatory response to cytosolic calcium, not influenced by inhibition of mitochondrial calcium uniporter channel. Therefore, our work identified calcium flow pathways among extracellular medium, cell cytosol, and ER by regulatory calcium channels. Particularly, extracellular calcium flow has an essential function to fully activate ER calcium release.

Obesity is a worldwide epidemic; hence it is crucial to understand how it can be effectively prevented/treated. Thus, obesity should be tackled considering that it is a multifactorial condition. This work examines a wide range of factors and attempts to understand which contribute most to variability in overweight/obesity. Eighty-four subjects with overweight/obesity were recruited. Dietary baseline information was obtained by analyzing three 24-hour recalls. Resting metabolic rate was measured using indirect calorimetry, physical activity through accelerometry, cardiometabolic parameters were determined in blood samples and body composition by anthropometry and bioimpedance. Factor analysis of principal components (PCA) was carried out (SPSS v22.0). Large interindividual variability was observed in dietetic, biochemical, and physical activity measurements (coefficient of variation ≥30%), but body composition was homogeneous. Volunteers had an unbalanced diet and low physical activity. PCA reduced the 26 analyzed variables into 7 factors, accounting for 81,5% of total data variability. The main factor was the ‘‘caloric and lipid factor’’ related to diet, responsible for 25.9% of total variability, followed by ‘‘adiposity factor’’ (16,9%) and ‘‘cardiometabolic risk factor’’ (13,2%). Diet seems to be the factor that contributes the most to data variability in people with overweight/obesity, especially the intake of lipids, energy and proteins.

Abstract: In this study, a computational fluid dynamics (CFD) simulation was conducted to validate the CFD model with experimental data from Zimparov et.al (2012), which investigates the heat transfer performance in a spirally corrugated tube that has a twisted tape inserted. The heat transfer was then compared to a simple corrugated tube without the twisted tape and to a smooth tube with no corrugations and no twisted tape. This simulation is compared with a previous experimental study conducted by (Zimparov et al. 2012), which focuses on tubes with a height-to-diameter ratio e/Di > 0.04 and small relative pitches of the twisted tape, H/Di. The largest improvement was noticed in the tube with e/Di= 0.057 and ridge pitch-to-height ratio p/e=6.77 with a twisted tape of H/Di= 4.7. This tube is labeled 5035. Tube 5035 was found to have the most significant enhancement, hence the focus of the CFD simulation will be on this tube, and the simulation will range for Reynolds numbers, 3.5 x 103 < Re < 5.0 x 104. The focus of this simulation is the evaluation of heat transfer and friction factors; a metric was used to obtain an empirical representation of the tube’s performance. Keywords: Spirally corrugated tube; Twisted tape; Heat transfer enhancement; Friction factor; Nusselt number; Computational fluid dynamics (CFD); Star CCM+

Non-alcoholic fatty liver disease (NAFLD), a frequent complication of metabolic syndrome and visceral obesity, is characterized by marked accumulation of lipids in hepatocytes, accompanied by oxidant stress. In a substantial minority of cases, this progresses to steatohepatitis, which in turn can lead to life-threatening hepatic fibrosis and/or hepatocarcinogenesis. This essay analyzes the molecular biology underlying fat accumulation and oxidant stress in NAFLD, and identifies targets that can be addressed by nutraceutical or dietary measures. Nutraceuticals with potential for prevention or control of NAFLD – as suggested on theoretical grounds, and borne out by experience in rodent studies and/or clinical trials - include ferulic acid, melatonin, methylnicotinamide, tetrahydrocurcumin, nicotinamide riboside, carnosic acid, urolithin A, quercetin, high-dose biotin, citrulline, astaxanthin, long-chain omega-3 fatty acids, berberine, lipoic acid, silibinin, N-acetylcysteine, taurine, capsaicin, spermidine, spirulina, and carnitine. Some of these agents can also address the NLRP3 inflammasome activation and transforming growth factor-β signaling that play a role in driving the transition to steatohepatitis and fibrosis. In addition, soy isoflavones, via estrogen receptor-beta agonism, have anti-fibrotic potential, and supplemental glycine may blunt the contribution of Kupffer cells to the progression of NAFLD. Whole-food plant-based diets of modest protein content, owing to their impact on hormones such as fibroblast growth factor 21 and adiponectin, as well as on the obesity and metabolic syndrome underlying NAFLD, may also be protective in this syndrome. There is considerable potential for complex medical foods or nutraceutical supplementation regimens of rational design to aid prevention and control of NAFLD.

A scientific carbon accounting system can help enterprises reduce carbon emissions. This study took the enterprise in the Yangtze River basin as a case study. The accounting classification of carbon emissions in the life cycle of lime production was assessed, and the composition of the sources of carbon emission was analyzed, covering mining explosives, fuel (diesel, coal), electricity and high temperature limestone decomposition. Using the IPCC emission factor method, a carbon life cycle emission accounting model for lime production was established. We determined that a total of 354,200 tons of carbon emissions were generated from producing 321,000 tons of lime in a year. The decomposition of limestone at a high temperature was the largest carbon emission source, accounting for 62.34% of the total carbon emission. Coal combustion was also an important source of carbon emissions, accounting for 32.66% of total carbon emissions. The carbon emission for one ton of activated lime was 1.46kg, 1.49kg, 1100kg and 1102.95kg respectively for the open-pit, mining stage, crushing stage, and the calcination stage. Based upon the main sources of carbon emission for lime production, carbon emission reduction should focus on CO2 capture technology, fuel optimization and energy control. Using our analysis of carbon emissions, the carbon emission factor of producing unit quicklime of the lime enterprise in the Yangtze River basin was determined. Furthermore, the research into carbon emission reduction for lime production can provide a point of reference for the promotion of carbon neutrality in the same industry.

Transcription factors are diverse intracellular proteins facilitating cellular responses to inducing factors via gene expression. Regulatory signalling cascades from the membrane proteins (sensors) to transcription factors (effectors) are paramount to accurate phenotypic display against external factors. This review examines several transcription factors germane to Cryptococcus (C.) neoformans adaptation and survival for human infection. These opportunistic pathogenic single-cell yeasts (fungi) possess several gene duplications and peculiar membrane proteins due to adaptive phenotypes and morphological plasticity. Consequently, hundreds of responsible pleiotropic genes have been studied to understand how these genes are induced, regulated, and coordinated. However, these findings are sparsely converged and interlinked, making it cumbersome to relate one gene to the other or group them by their functions. We reviewed several wide-ranging transcriptional analysis works associated with C. neoformans into comparable phenotypic traits that necessitate adaptation, survival, and human infection. We present a robust work that addresses several transcription factors and their inducing factors. Lastly, we converge, link, and group several of these factors according to their multifunctional expression pattern. We also provide adequate information on certain genes critical to this fungus, which could be explored pharmaceutically in drug targeting for more effective antifungal management.

How complex morphological patterns form is an intriguing question in developmental biology. However, the mechanisms that generate complex patterns remain largely unknown. Here we sought to identify the genetic mechanisms that regulate the tan (t) gene in a multi-spotted pigmentation pattern on the abdomen and wings of Drosophila guttifera. Previously, we showed that yellow (y) gene expression completely prefigures the abdominal [1] and wing [2] pigment patterns of this species. In the current study, we demonstrate that the t gene is co-expressed with the y gene in nearly identical patterns, both transcripts foreshadowing the adult abdominal and wing melanin spot patterns. We identified cis-regulatory modules (CRMs) of t, one of which drives reporter expression in six longitudinal rows of spots on the developing pupal abdomen, while the second CRM activates the reporter gene in a spotted wing pattern. Comparing the abdominal spot CRMs of y and t, we found a similar composition of putative transcription factor binding sites that are thought to regulate the complex expression patterns of both terminal pigmentation genes y and t. In contrast, the y and t wing spots appear to be regulated by distinct upstream factors. Our results suggest that the D. guttifera abdominal and wing melanin spot patterns have been established through the co-regulation of y and t, shedding light on how complex morphological traits may be regulated through the parallel coordination of downstream target genes.

This study was to determine the effects of different irrigation, fertigation and mulching applications on the yield and quality parameters of strawberries. The study was conducted at the Bursa Uludağ University Yenişehir Ibrahim Orhan Vocational School Agricultural Research Field in 2019-2020. In the research, four different irrigation topics, three different fertigation and three different mulching topics were selected The maximum and minimum yield values of the study years were calculated as 5.05-18.70 t ha-1 and 1.20-8.7 t ha-1, respectively, from I100F100M1 and I25F50M0 treatments. As a result, a three-factor study determined that irrigation, fertigation, and mulching had a significant effect on the yield and quality characteristics of strawberries. However, when the reductions in yield and quality losses are evaluated together, despite the reductions in irrigation water and fertigation levels, I75 and F75 topics can be recommended. Also, in mulching treatments, black mulch material (M1) should be chosen over clear mulch material (M1) and no mulch (M0).

The main regulatory factors during the adaptation of cancer cells to hypoxic stress are the hypoxia-inducible factors (HIFs), which are being increasingly recognized as an interesting and challenging target for the design of new chemotherapeutic molecules. HIF2A was found to have an large internal hydrophilic cavity within its PAS-B domain, unique to this sub-unit and is suggested to be a possible ligand-binding site. Regulation of HIF2A by cellular molecules is still greatly unknown. In This paper we have employed in-silico techniques, such as molecular docking and dynamic simulation, to design new direct inhibitors against HIF-2A subunit via targeting one of its critical domains and the final top screened molecules have been tested on hypoxic cancer cells for further validation of their inhibitory potential. we targeted the hydrophilic cavity inside the PAS-B domain of the HIF2A to identify novel molecules with a high binding capacity. Virtual Screening methodology was used for molecular docking of NSC library against the target domain inside the HIF2A PAS-B domain with the top 5% compounds with significant MolDock and Re-rank scores were selected for further analysis. The NSC 106416, NSC 217021, NSC 217026, and NSC 215639 compounds were selected based on their docking scores. NSC 215639 had the minimum polar solvation energy and also had a relative strong binding energy. NSC 217026 had the strongest binding energy among other compounds.

Since its inception in 2019, COVID-19 has been associated with significant changes in lifestyle-related behavior, including physical activity, diet, and sleep, which are vital to maintaining our well-being. This study measures lifestyle-related behavior during the COVID-19 pandemic lockdown using a 21-item questionnaire. The responses were collected from March 2021 to September 2021. Four hundred sixty-seven participants were engaged in assessing the changes caused by the pandemic and their effect on BMI. The validity and reliability of the questionnaire were tested for 71 participants. Cronbach's alpha values for the questionnaire all exceeded 0.7, demonstrating good validity and internal consistency for it. The effect of each question regarding physical activity and dietary habits over the BMI difference was studied using ANOVA. The study shows that more than half of the participants reported snacking more between meals and increased their sitting and screen time, while 74% felt more stressed and anxious. These indications were the cause of the increase in the BMI rate for individuals in the lockdown. In contrast, 62% of the participants showed more awareness about their health by increasing the intake of immunity-boosting foods, and 56% of the participants showed an increase in the consumption of nutrition supplements. Females and married individuals tended to be healthier, so their BMI showed stability compared to others based on their gender and marital status.

We explore the deflection angle in the framework of improved Schwarzschild Black hole utilizing the most advance geometrical path adopted by Gibbon-Werner. To investigate deflection angle of the photon ray by weak gravitational lensing for this black hole, we derive the optical curvature and perform the application of Gauss-Bonnet theorem on the optical metric. Moreover, we study the impacts of the plasma medium in context of the weak gravitational lensing in relate to this black hole. Further, we also study the graphical analysis of the deflection angle in both the plasma and non-plasma mediums. Also, we find the rigorous bound base upon the greybody factor for improved Schwarzschild black hole. A while later, we contrast our conclusions about deflection angle with the deflection angles of Schwarzschild black hole within plasma and non-plasma mediums.

Cemented rock fill (CRF) is commonly used in cut-and-fill stoping operation in underground mining. This allows for the maximum recovery of ore. Backfilling can improve stope stability in underground workings, and then improve ground stability of the whole mine site. Backfilling step scenarios vary from site to site. This paper presents the investigation of five different backfilling step scenarios and their impacts on the stability of stopes at four different mining levels. A comprehensive comparison of displacements, major principal stress and stress concentration factor (SCF) was conducted. The results show that different backfilling step scenarios have little influence on the final displacement for displacement in the stopes. Among the five backfilling scenarios, the major principal stress and stress concentration factor (SCF) have almost the same final results. The backfilling scenario SCN-1 is the optimum option among these five backfilling scenarios. It can immediately prevent the increase of the displacement and reduce the sidewall stress concentration, thereby preventing possible failures. Using the same strength of CRF can achieve same effects among the four mining levels. Applying backfilling CRF of the same strength at different mining depths is acceptable and feasible to improve the stability of the stopes.

Construction project management and cost management is a difficult process that affects the overall success of construction projects. The success of a construction project can be assessed according to key performance indicators (KPIs). Cost savings and cost optimization over the life of a construction project is one of these KPIs. Cost management is largely performed through intelligent information technology in the construction industry. Information systems and information technologies have seen an increase in use in the management of construction projects. The same goes for cost management. Several studies mentioned in the paper point to this increase in use in recent years also in the management of costs at various stages. Many studies point to the use of information technology and software applications in the field of cost management. Still, to a large extent, there are no surveys focused on the analysis of the impact and impact factor of information technology on cost savings or cost optimization in various phases of construction projects. The research discusses the issue of the impact of information technology on cost management in various phases of a construction project. The main goal of the research is to analyze the influence of information technology factors on cost savings and optimization in individual phases of a construction project. Several statistical methods were used in the research. The resulting model of information technology impact factor was created based on data processing and the use of the AHP method.

Enterovirus 71 (EV71) infection hand-foot-mouth disease (HFMD), meningoencephalitis, neonatal sepsis, and even fatal encephalitis in children, thereby representing a serious public health hazard. It is important to determine the mechanisms underlying the regulation of EV71 infection. In this study, we initially reveal that the interleukin enhancer binding factor 2 (ILF2) down-regulates EV71 50% tissue culture infective dose (TCID50), attenuates EV71 plaque formation unit (PFU), thereby repressing EV71 infection. Moreover, we reveal a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects. Chip data analyses show that ILF2 mRNA is reduced upon EV71 infection. Cellular studies indicate that EV71 infection represses ILF2 mRNA expression and protein production in human leukemic monocytes (THP-1) differentiated macrophages and in human rhabdomyosarcoma (RD) cells. Additionally, EV71 non-structural protein 2B interacts with ILF2 in human embryonic kidney (HEK293T) cells. Interestingly, in the presence of EV71 2B, ILF2 is translocated from the nucleus to the cytoplasm and co-localizes with 2B in the cytoplasm. Therefore, we reveal a distinct mechanism by which EV71 antagonizes ILF2-mediated antiviral effects by inhibiting ILF2 expression and promoting ILF2 translocation from the nucleus to cytoplasm through its 2B protein.

Indirubin-3′-monoxime (I3M) exhibits anti-proliferative activity in various cancer cells; however, its anti-cancer mechanism remains incompletely elucidated. This study revealed that I3M promotes the expression of death receptor 5 (DR5) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in HCT116 p53+/+ cells, resulting in caspase-mediated apoptosis. However, this study demonstrated that HCT116 p53-/- cells are insensitive to I3M-mediated apoptosis, indicating that I3M-induced apoptosis depends on the p53 status of HCT116 cells. Additionally, in HCT116 p53-/- cells, I3M significantly increased Ras expression, while in HCT116 p53+/+ cells, it reduced Ras expression. Furthermore, I3M remarkably increased the production of reactive oxygen species (ROS), which were reduced in transient p53 knockdown, indicating that I3M-mediated apoptosis is promoted by p53-mediated ROS production. Our results also showed that I3M enhanced transcription factor C/EBP homologous protein (CHOP) expression, resulting in endoplasmic reticulum (ER) stress-mediated DR5 expression, which is upregulated by ROS production in HCT116 p53+/+ cells. Moreover, co-treatment with TRAIL synergistically enhanced I3M-induced DR5 expression, thereby triggering TRAIL-induced apoptosis of HCT116 p53+/+ cells, which was interfered by a DR5-specific blocking chimeric antibody. In summary, I3M potently enhances TRAIL-induced apoptosis by upregulating DR5 expression via p53-mediated ROS production in HCT116 p53+/+ cells. However, HCT116 p53-/- cells were resistant to I3M-mediated apoptosis, suggesting that I3M could be a promising anti-cancer candidate against TRAIL-resistant p53+/+ cancer cells.

This study presents a new form of velocity distribution in laminar liquid flow in rectangular microchannels using the eigenfunction expansion technique. Darcy friction factor and Poiseuille number are also obtained analytically. Due to the symmetry of the solutions, the effects of changing the aspect ratio from 0 to ∞ are also discussed. Using finite element method (FEM), the obtained analytical results are further compared with the 3D numerical simulations for the rectangular microchannels with different range of aspect ratio and pressure gradient, and excellent agreements were found. These findings provide additional insights in interpreting the results of the pressure-driven flows in finite aspect ratio microchannels, in which very precise comparison with the macroscale theory is crucial.

The cellular stress response corresponds to the molecular changes that cell undergoes in response to various environmental stimuli. It induces drastic changes in the regulation of gene expression, at transcriptional and post-transcriptional levels. Actually, translation is strongly affected with a blockade of the classical cap-dependent mechanism, whereas alternative mechanisms are activated to support translation of specific mRNAs. One of the major mechanisms involved in stress-activated translation is the internal ribosome entry site (IRES)-driven initiation. IRESs, first discovered in viral mRNAs, are present in cellular mRNAs coding for master regulators of cell responses, whose expression must be tightly controlled. IRESs allow translation of these mRNAs in response to different stresses, including DNA damage, amino-acid starvation, hypoxia or endoplasmic reticulum stress, as well as to physiological stimuli such as cell differentiation or synapse network formation. Importantly, cellular mRNA IRESs are regulated by IRES trans-acting factor (ITAFs), exerting their action by at least nine different mechanisms. This review presents an update of the reported ITAFs regulating cellular mRNA translation and of the different mechanisms allowing them to control translation initiation in specific conditions. The impact of ITAFs on coordinated expression of mRNA families and consequences in cell physiology and diseases are also highlighted.

The details of antigen-antibody interactions and the identification of epitopes are critical for the development of monoclonal antibody drugs. Ab42 is a native human-derived anti-CFH monoclonal antibody. In this study, the interaction between antigen pCFH and antibody (Ab42) was theoretically demonstrated by molecular docking and MD simulation, combined with free energy calculation and computational alanine scanning (CAS), and key amino acids and epitopes were identified. Experimental alanine scanning (EAS) was then carried out to verify the results of the calculation, and our results indicated that Ab42 antibody forms hydrogen bonds and interacts hydrophobically with pCFH through the Tyr315, Ser100, Gly33, and Tyr53 residues on its CDR, while the main pCFH epitopes are located at the six sites of Pro441, Ile442, Asp443, Asn444, Ile447, and Thr448. In conclusion, this study has explored the mechanism of antigen-antibody interaction from both theoretical and experimental aspects, and our results have important theoretical significance for the design and development of relevant antibody drugs.

The application of thermoelectric generators (TEG) on the nozzle of an aviation jet engine was studied by finite element TEG-simulations. Against the background of system-level requirements of the reference aircraft this work reports the resulting requirements on the TEG design with respect to applied thermoelectric (TE) element lengths and fill factors (F) within the TE modules in order to maintain a positive effect on the specific fuel consumption. Assuming a virtual optimized TE material and varying the convective heat transfer coefficients at the nozzle surfaces this work reports the achievable power output. System-level requirement on the gravimetric power density (> 100 Wkg-1) can only be met for F ≤ 21%. Extrapolating TEG coverage to the full nozzle surface, the power output reaches 1.65 kW per engine. Assessment of further potential is demonstrated by a parametric study on the fill factor, convective heat transfer coefficients, and materials performance. This study confirms a feasible design range for TEG installation on the aircraft nozzle with a positive impact on the fuel consumption. This application translates into a reduction of operational costs, allowing for an economically efficient installation of TEG in consideration of the cost-specific power output of modern thermoelectric materials.

The Colebrook equation is a popular model for estimating friction loss coefficients in water and gas pipes. The model is implicit in the unknown flow friction factor . To date, the captured flow friction factor can be extracted from the logarithmic form analytically only in the term of the Lambert -function. The purpose of this study is to find an accurate and computationally efficient solution based on the shifted Lambert -function also known as the Wright -function. The Wright -function is more suitable because it overcomes the problem with the overflow error by switching the fast growing term of the Lambert -function to the series expansions that further can be easily evaluated in computers without causing overflow run-time errors. Although the Colebrook equation transformed through the Lambert -function is identical to the original expression in term of accuracy, a further evaluation of the Lambert -function can be only approximate. Very accurate explicit approximations of the Colebrook equation that contains only one or two logarithms are shown. The final result is an accurate explicit approximation of the Colebrook equation with the relative error of no more than 0.0096%. The presented approximations are in the form suitable for everyday engineering use, they are both accurate and computationally efficient.

Improving air quality and reducing human exposure to unhealthy levels of airborne chemicals are important global missions, particularly in China. Satellite remote sensing offers a powerful tool to examine regional trends in NO2, thus providing a direct measure of key parameters that strongly affect surface air quality. To accurately resolve spatial gradients in NO2 concentration using satellite observations and thus understand local and regional aspects of air quality, a priori input data at sufficiently high spatial and temporal resolution to account for pixel-to-pixel variability in the characteristics of the land and atmosphere are required. In this paper, we adapt the Berkeley High Resolution product (BEHR v3.0A, v3.0B and v3.0C) and meteorological outputs from the Weather Research and Forecasting (WRF) model to describe column NO2 in southern China. The BEHR approach is particularly useful for places with large spatial variabilities and terrain height differences such as China. We retrieved tropospheric NO2 vertical column density (TVCD) within part of southern China, for four seasons of 2015, based upon satellite datasets from Ozone Monitoring Instrument (OMI). Retrieval results are validated by comparing with MAX-DOAS tropospheric column measurements conducted in Guangzhou. BEHR retrieval algorithms are more consistent with MAX-DOAS measurements than OMI-NASA retrieval, opening new windows into research questions that require high spatial resolution, for example retrieving NO2 vertical column and ground pollutant concentration in China and other countries.

This paper generalizes the actuator disc theory to the application of crosswind kite power systems. For simplicity, it is assumed that the kite sweeps an annulus in the air, perpendicular to the wind direction (i.e. straight downwind configuration with tether parallel to the wind). It is further assumed that the wind flow has a uniform distribution. Expressions for power harvested by the kite is obtained, where the effect of the kite on slowing down the wind (i.e. the induction factor) is taken into account. It is shown that although the induction factor may be small for a crosswind kite (of the order of a few percentage points), neglecting it in calculations may result in noticeable overestimation of the amount of power harvestable by a crosswind kite system.

The (benzylthio)acetic acid (HBTA) and some aminopyrimidines, namely 2-aminopyrimidine (2-AP), 5-aminopyrimidine (5-AP), 2-amino-4,6-dimethylpyrimidine (2-A-4,6-DMP) and 2,4,6-triaminopyrimidine (2,4,6-TAP), were successfully embodied as structural units into the construction of a total of four novel supramolecular organic frameworks. The received crystalline solids were inspected by single crystal X-ray diffraction (SC XRD) in order to obtain insight into the structural and supramolecular facets. The SOFs deriving from 2-AP, 5-AP as well as 2-A-4,6-DMP crystallize in the form of true co-crystals (1-3), while the one originating from 2,4,6-TAP crystallizes as salt solvate (4). The SC XRD results indicated the different contents of structural residues present in the asymmetric units of the crystals 1-4 despite the using the same molar ratio of molecular co-formers in each case. The molecular structures of co-crystals 1-3 consist of either one neutral residue of each starting components (1 and 3) or a half nonionized residue of aminopyrimidine ingredient and one neutral residue of acidic specie (2). The asymmetric unit of salt solvate 4 is composed of two ionized residues of each co-former (two 2,4,6-TAP+ cations and two BTA- anions) and one MeOH solvent molecule. The most extensive H-bonding network is observed in the crystal structure of salt solvate 4. The relevant molecular ingredients in co-crystals 1-3 are mainly hold together by the neutral Ocarboxylic–H···Npyrimidine and Namine–H···Ocarboxylic H-bonds. In the case of aggregate 4, the corresponding ionic residues are predominantly sustained by the charged-assisted Npyrimidinium–H···Ocarboxylate and Namine–H···Ocarboxylate hydrogen interactions. The MeOH solvent incorporated into the crystal lattice of adduct 4 is also involved in H-bonding by simultaneously serving as the single donor in OMeOH–H···S and the single acceptor in Namine–H···OMeOH H-bonds afforded the structural diversity within the 2,4,6-TAP+ cations and BTA- anions. Other weaker sets of additional non-covalent contacts existing in the crystal structures of analyzed conglomerates are involved in the self-assembly, stabilization and expansion of total supramolecular organic frameworks. The fact of the formation of non-covalent bonded supramolecular organic frameworks in question is also reflected in corresponding results obtained through elemental analysis (EA), Fourier transform infrared spectroscopy (FT−IR) and thermal analysis (TG/DSC).

The extremely controversial conclusions about the function of human interferon-gamma (hIFNγ) C-terminus as well as the lack of a consistent model explaining its role in the receptor binding prompted us to scrutinize the interaction of hIFNγ with its extracellular receptor hIFNGR1 in different scenarios by means of molecular dynamics simulations. We find that the two molecules alone fail to form a stable complex but the presence of heparan-sulfate-like oligosaccharides largely facilitates the process by both demobilizing the highly flexible C-termini of the cytokine and assisting in the proper positioning of its globule between the receptor subunits. An antiproliferative-activity essay on cells depleted from surface sulfation confirms qualitatively the simulation-based multistage complex-formation model. Our results reveal the key role of HS and its proteoglycans in all processes involving hIFNγ signalling.

The complete regression of clear cell renal cell carcinoma (ccRCC) obtained pre-clinically with anti-carbonic anhydrase IX (CAIX) G36 chimeric antigen receptor (CAR) T cells in doses equivalent to 10e8 CAR T cells/ Kg renewed the potential of this target to treat ccRCC and other tumors in hypoxia. The immune checkpoint blockade (ICB) brought durable clinical responses in advanced ccRCC and other tumors. Here we tested CD8/4-1BB compared to CD28-based anti-CAIX CAR PBMCs cells-releasing anti-programmed cell death ligand-1 (PD-L1) IgG4 for human ccRCC treatment in vitro and in an orthotopic NSG mice model in vivo. Using a 10e7 CAR PBMCs cells/ Kg dose, anti-CAIX CD28 CAR T cells releasing anti-PD-L1 IgG highly decrease both tumor volume and weight in vivo, avoiding the occurrence of metastasis. This antitumoral superiority of CD28-based CAR PBMCs cells compared to 4-1BB occurred under ICB via PD-L1. Furthermore, T cell exhaustion status in peripheral CD4 T cells, additionally to CD8 was critical for CAR T cells efficiency. The lack of hepatotoxicity and nephrotoxicity upon administration of 10e7 CAR PMBCs cells/Kg dose is the basis for carrying out clinical trials using anti-CAIX CD28 CAR PBMCs cells releasing anti-PD-L1 antibodies or anti-CAIX 4-1BB CAR T cells, offering exciting new prospects for the treatment of refractory ccRCC and hypoxic tumors.

Directional protective relaying based on amplitude comparison of traveling wave on continuous co-phase auto-transformer(AT) power transmission system was proposed. Phase-model transformation is used for decoupling transient fault signals and get aerial mode component. The forward and backward traveling wave are obtained by calculating aerial mode component, then the intrinsic mode function(IMF) components can be obtained through Variational Mode Decomposition(VMD), the module maxima are obtained through calculating the IMF components. The fault direction is determined by the ratio of fault components. If two faults relays at the ends of electric traction networks detect a fault to be in the forward direction, the fault occurred in the internal area, the protection would operate properly. The simulation tests indicate that the protection scheme is feasible, and the proposed protection method can discriminate internal faults from external faults under various fault types, and its performances are immune to fault initial angle, ground resistance, etc.

Data from Earth Observation (EO) satellites are increasingly used to monitor the environment, understand variability and change, inform evaluations of climate model forecasts and manage natural resources. Policy makers are progressively relying on the information derived from these datasets to make decisions on mitigating and adapting to climate change. These decisions should be evidence based, which requires confidence in derived products as well as the reference measurements used to calibrate, validate or inform product development. In support of the European Union’s Earth Observation Programmes Copernicus Climate Change Service, the Quality Assurance for Essential Climate Variables (QA4ECV) project fulfilled a gap in the delivery of climate quality satellite derived datasets by prototyping a robust, generic system for the implementation and evaluation of Quality Assurance (QA) measures for satellite-derived ECV climate data record products. The project demonstrated the QA system on six new long-term, climate quality ECV data records for surface Albedo, Leaf Area Index, FAPAR, NO₂, HCHO and CO. Provision of standardized QA information provides data users with evidence-based confidence in the products and enables judgement on the fitness-for-purpose of various ECV data products their specific applications.

Though Cyber Physical Systems (CPS) become very popular in last the decade, dependability of CPS is still a critical issue and related survey is rare. We try to spell out the jigsaw of technologies and figure out the technical trends of dependable self-managing CPS. This survey first recalls the motivation and the similar concepts. By analyzing four generic architectures, we summarize the common characteristics and related assurance technologies, and propose a more generic environment-in-loop processing flow of CPS and a formal interaction flow between physical space and cyber space. Further, the similarity between correctness and dependability is formally analyzed and the new five research questions of dependable self-managing CPS are presented. Then we review the critical technologies and related correctness verification & validation (V&V) methods, the architectures for dependable self-managing CPS. Further, the detail dependability management and V&V technologies are surveyed, which covers the areas of running-time fault management methods and whole life cycle V&V technologies, maintenance and available tool sets. For holistic CPS development, Modeling techniques and MDE (model driven engineering) based V&V methods are analyzed in detail. Then we complete the jigsaw of technologies and figure out the missing part. Further, we propose the technical challenges and the further direction. To our best knowledge, this is the first comprehensive survey on dependable self-managing CPS development and evaluation.

Abstract: The study used whole-genome sequencing (WGS) and bioinformatics analysis for the genomic characterization of 60 isolates of Listeria monocytogenes isolated from cattle farms, cattle abattoirs, and retail outlets in Gauteng province, South Africa. The isolates' sequence types (STs), clonal complexes (CCs), and lineages were determined using in silico multilocus sequence typing (MLST). We used BLAST-based analyses to identify virulence and antimicrobial genes, plasmids, proviruses, and the CRISPR-Cas system. The study investigated any association of the detected genes to the origin in the beef production chain of the L. monocytogenes isolates. Overall, in 60 isolates of Listeria monocytogenes, there were 7 STs, 6 CCs, 44 putative virulence factors, 2 resistance genes, 1 plasmid with AMR genes and 3 with conjugative genes, 1 CRISPR gene, and all 60 isolates were positive for proviruses. Among the 7 STs detected, ST204 (46.7%) and ST2 (21.7%) were the most prominent, with ST frequency varying significantly (p&lt;0.001). The predominant CC detected were CC2 (21.7%) and CC204 (46.7%) in lineages I and II, respectively. Of the 44 virulence factors detected, 26 (across Listeria Pathogenicity Islands, LIPIs) were present in all the isolates. The difference in the detection frequency varied significantly (P&lt;0.001). The two AMR genes (fosX and vga(G)) detected were present in all 60 (100%) isolates of L. monocytogenes. The only plasmid, NF033156, was present in 3 (5%) isolates. A CRISPR-Cas system was detected in 6 (10%), and all the isolates carried proviruses. Significant differences were detected in the frequencies of STs and virulence factors regarding the source and sample type of the L. monocytogenes isolates. The presence of both fosX and vga(G) genes in all the isolates from the three industries (cattle farms, abattoirs, and retail outlets) can potentially cause therapeutic implications. Our study, which characterized L. monocytogenes recovered from the three levels in the beef production chain in the country, provides the first evidence of the distribution of the pathogen with potential food safety and therapeutic implications.

In India, particularly within its North-Eastern territories, the occurrence of landslides triggered by post-dry period rainfall events is a significant concern, with the phenomena persistently causing extensive damage to both life and infrastructure. Despite the inevitability of such natural disasters, it is understood that the impact they exert can be substantially mitigated through the implementation of pre-emptive measures. Critical to the endeavour of landslide prevention is the application of a spectrum of mitigation strategies, predicated upon a foundational analysis of slope stability to ascertain critical surfaces for intervention. This investigation delves into the dynamics of partially saturated soils, a condition commonly resultant from the prolonged dry periods preceding the monsoonal rains. The study's focal point is an experimental examination conducted on soil samples to assess parameters such as soil matric suction and unconfined compressive strength across varying degrees of saturation and density, alongside performing analyses of slope failure incidents after dry period during the 2017 monsoon in the Lunglei district, Mizoram based on some established data. The Soil-Water Characteristic Curve (SWCC), derived from soil suction measurements employing the ASTM D5298-10 standard, utilizes a contact filter paper method and serves to delineate the moisture transition phases of the slope. To replicate the desiccation of the soil slope after monsoonal rains, a microwave drying technique based on the ASTM standard was employed to prepare unsaturated soil samples for Unconfined Compressive Strength (UCS) testing. The integrity of the slope was evaluated in a temporal context, before and after rainfall events of varied intensities throughout the calendar year, utilizing a blend of numerical modeling and empirical laboratory investigations. The persistence of real onsite slope failures underscores the necessity for a numerical analysis approach to unravel the underlying factors causing slope instability, especially given the absence of prior stability assessments for the landslide in question. An evaluation of SWCC curves, UCS tests on partially saturated soil at different densities and saturation and the utilization of the benchmark data collected in 2017 on the shallow transitional landslide in Lunglei, Mizoram caused by intense monsoonal precipitation, are central key data and information used to carry out this research. Rainfall data for Lunglei, sourced from the Mizoram Meteorological Department, facilitated a real-time monsoonal data-driven numerical analysis. This analysis elucidated the pivotal role of rainfall in inducing slope failure, indicating a marked destabilization of the slope after precipitation events. The implications of these findings are far-reaching, suggesting a foundational basis for the development of an advanced landslide early warning system, thereby enhancing disaster preparedness, and mitigating potential damages.

Abstract Background In tumors, somatic mutagenesis presumably drives DNA damage response (DDR) via altered regulatory pathways increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation activated DNA repair pathways of tumors. Purpose Justifying that cancer cells are not enemies to be killed, but rather they are ill human cells having the remnants of physiologic regulatory pathways. Results 1. Genomic instability and cancer development may be originated from the flaw of estrogen signal rather than excessive estrogen signaling. 2. Healthy cells with genomic instability exhibit somatic mutations helping DNA restitution. 3. Somatic mutations in tumor cells aim the restoration of DNA damage rather than further genomic derangement. 4. In tumors, estrogen signal drives the pathways of DNA stabilization leading to apoptotic death. 5. In the peritumoral cellular infiltration, the genomic damage of tumor induces inflammatory cytokine secretion and increased estrogen synthesis. In the inflammatory cells, increased growth factor receptor (GFR) signal confers unliganded activation of estrogen receptors (ERs). 6. In tumor cells responsive to genotoxic therapy, constitutive mutations help the upregulation of estrogen signal and consequential apoptosis. In tumors non responsive to genotoxic therapy, the possibilities for ER activation via either liganded or unliganded pathway, are exhausted leading to farther genomic instability and unrestrained proliferation. Conclusion Understanding the real character and behavior of human tumors at molecular level suggests that we should learn the genome repairing methods of tumors and follow them by supportive therapy rather than provoking additional genomic damages.

Depression is the commonest mental disorder worldwide. Both antidepressants and psychotherapy are effective in treating depression, but response to these treatments is often incomplete. Yoga-based interventions (YBIs) have emerged as a promising adjunctive treatment for depression. Recent research has attempted to identify the biological mechanisms associated with the antidepressant actions of YBIs. In this scoping review, conducted according to the PRISMA-ScR guidelines, the PubMed and Scopus databases were searched to retrieve research on biomarkers of response to YBIs in patients with depression. Eleven studies were included in the review. Based on these studies, YBIs may improve depression through beneficial effects on systemic inflammation, stress axis regulation, cardiac autonomic functioning, and possibly reductions in oxidative stress-related cellular damage. Increases in brain-derived neurotrophic factor (BDNF) may represent a final common pathway upon which these processes converge. Though these results are theoretically plausible, they should be interpreted with caution due to certain methodological limitations in the existing research. Replication of these results and improvements in study methodology, and the evaluation of other biomarkers relevant to the pathophysiology of depression, could further elucidate the mechanism of action of YBIs in this disorder, and identify which patients would benefit most from this treatment approach.

Diabetic retinopathy (DR), a prevalent complication of diabetes mellitus affecting a significant portion of the global population, has long been viewed primarily as a microvascular disorder. However, emerging evidence suggests that it should be redefined as a neurovascular disease with multifaceted pathogenesis rooted in oxidative stress and advanced glycation end products. The transforming growth factor-β (TGF-β) signaling family has emerged as a major contributor to DR pathogenesis due to its pivotal role in retinal vascular homeostasis, endothelial cell barrier function, and pericyte differentiation. However, the precise roles of TGF-β signaling in DR remain incompletely understood, with conflicting reports on its impact in different stages of the disease. Additionally, the BMP subfamily within the TGF-β superfamily introduces further complexity, with BMPs exhibiting both pro- and anti-angiogenic properties. Furthermore, TGF-β signaling extends beyond the vascular realm, encompassing immune regulation, neuronal survival, and maintenance. The intricate interactions between TGF-β and reactive oxygen species (ROS), non-coding RNAs, and inflammatory mediators have been implicated in the pathogenesis of DR. This review delves into the complex web of signaling pathways orchestrated by the TGF-β superfamily and their involvement in DR. A comprehensive understanding of these pathways may hold the key to developing targeted therapies to halt or mitigate the progression of DR and its devastating consequences.

Age-related macular degeneration (AMD) is an eye disease and the most common cause of vision loss in the Western World. In its advanced stage, AMD occurs in two clinically distinguished forms: dry and wet, but only wet AMD is treatable. However, the treatment based on repeated injections with vascular endothelial growth factor A (VEGFA) antagonists may at best stop the disease progression and prevent or delay vision loss but without an improvement of visual dysfunction. Moreover, it is a serious mental and financial burden for patients and may be linked with some complications. The recent first success of intravitreal gene therapy with ADVM-022, which transformed retinal cells to continuous production of aflibercept, a VEGF antagonist, after a single injection, has opened a revolutionary perspective in wet AMD treatment. Promising results obtained so far in other ongoing clinical trials support this perspective. In this narrative/hypothesis review, we present basic information on wet AMD pathogenesis and treatment, the idea of gene therapy in retinal diseases, update evidence on completed and ongoing clinical trials with gene therapy for wet AMD, and perspectives on the road to the clinic of “one and done” therapy for wet AMD to replace a lifetime of injections. Gene editing targeting the VEGFA gene is also presented as another gene therapy strategy to improve wet AMD management.

We are introducing a highly efficient 48-channel ultrasound beamforming system ideal for ultrasound endoscopy applications. The system includes a transmitter and a receiver, which allow for low-area, high-resolution imaging acquisition. The transmitter uses a charge redistribution HV (high voltage) scheme to generate three-level pulses that actuate the transducer, implemented with the standard CMOS process for optimal cost and power savings. Meanwhile, the receiver features a sub-array structure and a delay generator that reduces area usage. To achieve high-resolution ultrasound imaging acquisition with low computational power, we developed the Shift Coherence Factor (SCF) algorithm, which is hardware-friendly. This approach delivers a lateral resolution over 20% better than the conventional delay and sum (DAS) algorithm, with a contrast ratio of over 30 dB. The system was implemented in a 180 nm standard CMOS process with an area of 24.98 mm2, power consumption of 8.23 mW per channel, achieving a delay resolution of 8.33 ns, and a low-area implementation of 0.52 mm2 per channel. The system offers high-quality imaging acquisition with minimal additional area and power consumption, which has great potential for 3D imaging or catheterized ultrasound systems.

The loss or dysfunction of skeletal tissue often necessitates surgical intervention, particularly in cases involving trauma, tumors, or abnormal development leading to critical-sized defects. Despite autografts being considered the gold standard for bone grafts, their limitations and complications prompt the exploration of alternative approaches for bone repair and regeneration. Current advancements in bone tissue engineering have led to innovative strategies aiming to regenerate injured bone structures, providing viable alternatives to traditional autografts or allografts. Among these strategies, Hydrogel Microparticles (HMPs) have emerged as promising scaffolds due to their notable characteristics, including high porosity and mechanical tunability. HMPs play an important role in facilitating vasculature formation, mineral deposition, and overall bone tissue regeneration. HMPs, fabricated through various techniques, exhibit versatility in functions such as drug and cell delivery, structural scaffolding, and bioinks for 3D printing. In addition, these microgels can be injected for minimally invasive delivery and can display modular properties with different designs and configurations. This review exclusively focuses on the advancements in HMPs for bone regeneration, delving into synthesis and functionalization techniques while highlighting their diverse applications documented in the literature. Our aim is to shed light on the unique benefits and potential of HMPs in the intricate field of engineering bone tissue.

Brain-derived neurotrophic factor (BDNF) is a key molecule in promoting neurogenesis, dendritic and synaptic health, and neuronal survival, plasticity, and excitability, all of which are disrupted in neurological and cognitive disorders such as Alzheimer’s disease (AD). Extracellular aggregates of amyloid-β (Aβ) in the form of plaques and intracellular aggregates of hyperphosphorylated tau protein have been identified as major pathological insults in AD brain, along with immune dysfunction, oxidative stress, and other toxic stressors. Although aggregated Aβ and tau lead to decreased brain BDNF expression, early losses in BDNF prior to plaque and tangle formation may be due to other insults such as oxidative stress and contribute to early synaptic dysfunction. Physical exercise, on the other hand, protects synaptic and neuronal structure and function, with increased BDNF as a major mediator of exercise-induced enhancements in cognitive function. Here, we review recent literature on mechanisms behind exercise induced BDNF upregulation and its effects on improving learning and memory and on Alzheimer’s disease pathology. Mechanisms include elevations in peripheral BDNF-inducing hormones such as osteocalcin, FNDC5/irisin, and lactate. The fundamental mechanisms of how exercise impacts BDNF and cognition are unclear but are a prerequisite to developing new biomarkers and therapies to delay or prevent cognitive decline.

Today, the most powerful approach to detect distant homologs of a protein is based on structure prediction and comparison. Yet this approach is still inapplicable to many viral proteins. Therefore, we developed a powerful sequence-based procedure to identify distant homologs of viral proteins. It relies on 3 main principles: 1) Traces of sequence similarity with a protein can persist beyond the significance cutoff of homology detection programs; 2) Candidate homologs can be identified among proteins with weak sequence similarity to the query, by using "contextual" information, e.g. taxonomy or type of host infected; 3) These candidate homologs can be validated using highly sensitive profile-profile comparison.As a test case, we applied our approach to a protein without known homologs, ORF4 of Lake Sinai virus (which infects bees). We discovered that ORF4 is composed of a domain that has homologs in proteins from >20 taxa of viruses infecting arthropods. We called it “Widespread, Intriguing, Versatile” (WIV) domain because it is found in proteins with a wide variety of domain organizations and functions. For example, WIV is encoded by the NSs protein of tospoviruses, a global threat to food security, which infect plants through arthropod vectors; by the protein encoded by RNA2 ORF1 of chronic bee paralysis virus, a widespread virus of bees; and by various proteins of cypoviruses, which infect the silkworm bombyx mori. WIV has a previously unknown structural fold, according to Alphafold predictions. In some viral species, WIV facilitates infection of arthropods, according to bibliographical evidence

The potentially active A subunit of coagulation factor XIII (FXIII-A) is an intracellular transglutaminase expressed in various cell types including platelets and monocytes/macrophages. It is involved in stabilizing protein structures by cross-linking through Nε-(?-L-glutamyl)-L-lysyl iso-peptide bonds. Macrophages are major cellular constituents of the atherosclerotic plaque and are important in determining its structural/functional features. Two of their important functions are the accumulation of oxidized LDL in the lipid core, and by cross-linking structural proteins they may stabilize the plaque and protect the thrombi of atherogenic origin against fibrinolytic degradation. It is important to know whether these functions operate in parallel utilizing the same cellular compartments. First, we showed that monocyte-derived human macrophages significantly increase their FXIII-A content when up-taking oxidized LDL. This phenomenon is very likely independent of the process of transformation into foam cells, as the transformation of vascular smooth muscle cells into foam cells fails to result in the expression of FXIII-A. FXIII containing macrophage-like cells are abundant in the plaque and FXIII-A is also present in the extracellular core. Several cells co-stained for FXIII-A and for Oil Red O suggest that expression of FXIII-A and lipid up-take are common features of macrophages present in the atherosclerotic plaque.

Hypotrochoidal profile contours have been produced in industrial applications in recent years using twin-spindle processes, and they are considered effective high-quality solutions for positive shaft–hub connections. This study mainly concerns analytical approaches to determine the bending stresses in hypotrochoidal profile shafts. The formulation was developed according to bending principles using the mathematical theory of elasticity and conformal mappings. The loading was further used to investigate the rotating bending behaviour. The stress factors for the classical calculation of maximum bending stresses were also determined for all those profiles presented and compiled in the German standard DIN3689-1 for practical applications. The results were also compared with the corresponding numerical and experimental results, and very good agreement was observed. Additionally, based on previous work, the stress factor was determined for the case of torsional loading to calculate the maximum torsional stresses in the standardised profiles, and the results are listed in a table. This study contributes to the further refinement of the current DIN3689 standard.

Antimicrobial resistance (AMR) has been a serious threat to human health, and combination therapy is proved to be an economic and effective strategy to fight the resistance. However, the abuse of drug combinations would conversely accelerate the spread of AMR. In our previous work, it had been concluded that the mutant selection indexes (SIs) of one agent against a specific bacterial strain are closely related to the proportions of two agents in a drug combination. To discover probable correlations, predictors and laws for further proposing feasible principles and schemes guiding the AMR-preventing practice, here three aspects were further explored. First, the power function (y=ax^b, a > 0) correlation between the SI (y) of one agent and the ratio value (x) of two agents in a drug combination was further established based on the mathematical and statistical analyses for those experimental data, and two rules a₁ × MIC₁ = a₂ × MIC₂ and b₁ + b₂ = -1 were discovered from both equations of y=a₁x^b1 and y=a₂x^b2 respectively for two agents in drug combinations. Simultaneously, it was found that one agent with larger MPC alone for drug combinations show greater potency for narrowing itself MSW and preventing the resistance. Second, a new concept as mutation-preventing selection index (MPSI) was proposed and used for evaluating the mutation-preventing potency difference of two agents in drug combinations, and the positive correlation between the MPSI and the mutant prevention concentration (MPC) or minimal inhibitory concentration (MIC) was subsequently established. Inspired by this, the significantly positive correlation, contrary to previous reports, between the MIC and the corresponding MPC of antimicrobial agents against pathogenic bacteria was established using one hundred and eighty-one of data pairs reported. These results together of above three aspects indicate that the MPCs in alone and combination are very important indexes for drug combinations to predict the mutation-preventing effects and the trajectories of collateral sensitivity, and while the MPC of an agent can be roughly calculated from its corresponding MIC. Subsequently, the former conclusion was further verified and improved by the antibiotic exposure to forty-three groups designed as different drug concentrations and various proportions. The results further proposed that the C/MPC for the agent with larger proportion in drug combinations can be considered as a predictor and is the key to judge whether the resistance and the collateral sensitivity occur to two agents. Based on these above correlations, laws, and their verification experiments, some principles were proposed, and a diagram of the mutation-preventing effects and the resistant trajectories for drug combinations with different concentrations and ratios of two agents was presented. Simultaneously, the reciprocal of MPC alone (1/MPC), proposed as the stress factors of two agents in drug combinations, together with their SI in combination, is the key to predict the mutation-preventing potency and control the trajectories of collateral sensitivity. Finally, a preliminary scheme for antimicrobial combinations preventing the AMR was further proposed for subsequent improvement research and clinic popularization, based on the above analyses and discussion. Moreover, some similar conclusions were speculated for triple or multiple drug combinations.

Lung cancer is a common malignant tumor of the lung and the leading cause of cancer mortality worldwide. Non-small-cell lung cancer (NSCLC) accounts for 80%–85% of lung cancer, 40% of NSCLCs will have spread beyond the lungs by the time it is diagnosed. Long non-coding RNA (LncRNA) prostate androgen-regulated transcript 1 (PART-1) was reported that promote the development of several cancers. In the current study, we conducted experiments to investigate the role of PART-1 in the proliferation, invasion, and migration of NSCLC. The expression level of the PART-1 gene increased significantly in the NSCLC cell lines, including A549, H1229, H1650, H1975, and PC9. Knocking down of PART-1 inhibited the proliferation, invasion, and migration of A549 cells, moreover, decreased the tumor proliferation in nude mice. We confirmed that PART-1 targeted miR-204-3p directly, and miR-204-3p targeted the insulin-like growth factor binding protein 2 (IGFBP-2) directly. Furthermore, we discovered that PART-1 involved the NSCLC progression by regulating the miR-204-3p-targeted IGFBP-2 pathway. LncRNA PART-1 might be a target for treating NSCLC, and a warning sign of diagnosis of early lung cancer.

According to current guidelines, growth hormone (GH) therapy is strongly recommended in children and adolescents with GH deficiency (GHD) in order to accelerate growth rate and attain normal adult height. The diagnosis of GHD requires demonstration of decreased GH secretion in stimulation tests, below the established threshold value. Currently, GHD in children is classified as secondary insulin-like growth factor-1 (IGF-1) deficiency. Most of children diagnosed with isolated GHD presents with normal GH secretion at the attainment of near-final height or even in mid-puberty. The most important clinical problems, related to the diagnosis of isolated GHD in children and to optimal duration of rhGH therapy include: arbitrary definition of subnormal GH peak in stimulation tests, disregarding factors influencing GH secretion, insufficient diagnostic accuracy and poor reproducibility of GH stimulation tests, discrepancies between spontaneous and stimulated GH secretion, clinical entity of neurosecretory dysfunction, discrepancies between IGF-1 concentrations and results of GH stimulation tests, significance of IGF-1 deficiency for the diagnosis of GHD, a need for validation IGF-1 reference ranges. Many of these issues have remained unresolved for 25 years or even longer. It seems that finding solutions to them should optimize diagnostics and therapy of children with short stature.

Partial shading on solar photovoltaic (PV) arrays is a prevalent problem in photovoltaic systems that impair the performance of PV modules and is responsible for reduced power output as compared to that in standard irradiance conditions thereby resulting in the appearance of multiple maximas on panel output power characteristics. These maxims contribute to mismatch power losses among PV modules. The mismatch losses depend on shading characteristics together with different interconnected configuration schemes of PV modules. The research presents a comparative analysis of partial shading effects on a 4 x4 PV array system connected in series(S), parallel (P), serries-parallel (SP),total-cross-tied (TCT),central-cross-tied(CCT),bridge-linked(BL),bridge-linked total cross-tied (BLTCT) ,honey-comb(HC), honey-comb total-cross-tied (HCTCT) and ladder (LD) configurations using MATLAB/Simulink. The PV module SPR-X20-250-BLK was used for modeling and simulation analysis. Each module is comprised of 72 number of PV cells and a combination of 16 PV modules was employed for the contextual analysis. Accurate mathematical modeling for the HCTCT configuration under partial shading conditions (PSCs) is provided for the first time and is verified from the simulation. The different configuration schemes were investigated under short-narrow,short-wide,long-narrow,long-wide, diagonal, entire row distribution, and entire column distribution partial shading condition patterns with mathematical implementation and simulation of passing clouds. The performance of array configurations is compared in terms of maximum power generated ), mismatch power loss (∆), relative power loss ) and the fill factor (FF). It was inferred that on average, TCT configuration yielded maximum power generation under all shading patterns among all PV modules interconnection configurations with minimum mismatch power losses followed by hybrid and conventional PV array configurations respectively.

Lung cancer is the most common malignancy across the world. The new era in lung cancer treatments, especially this past decade, has yielded novel categories of targeted therapy for specific mutations and adjuvant therapy, both of which have led to improved survival rates. In the present study, we review the changes and development of treatments, with a special focus on adjuvant therapy using tyrosine kinase inhibitors (TKIs) administered to non-small-cell lung carcinoma patients who had a complete resection of the tumor harboring a mutated epidermal growth factor receptor. The clinical trials are dating from the past (chemotherapy trials), present (TKIs) and future (ongoing trials).

Insulin-like growth factor binding proteins (IGFBPs) are critical modulators of the metabolism. In adults, IGFBPs are associated with obesity and insulin resistance but the association of IGFBPs with metabolic homeostasis in children and adolescents is not fully characterized. In this study we investigated the association of plasma IGFBPs (IGFBP-1, 3 and 7) with weight status, central adiposity and cardiovascular disease markers Hs-CRP and Ox-LDL. A total of 420 adolescents (age 11-14 years) were randomly recruited from public middle schools in Kuwait. IGFBPs were measured using bead-based multiplexing while Hs-CRP and Ox-LDL were measured using ELISA. IGFBP-1 levels were significantly lower in obese and overweight participants compared to normal weight children. Only IGFBP-1 was negatively associated with waist circumference to height (WC/Ht) ratio. IGFBP-1 was negatively correlated with Hs-CRP while IGFBP-3 and IGFBP-7 were negatively correlated with Ox-LDL. These data demonstrate a robust negative association of IGFBP-1, but not IGFBP-3 or -7, with overweight and obesity, and the inflammation marker Hs-CRP. Central adiposity (WC/Ht ratio) was a stronger predictor of IGFBP-1 than BMI-for-age z-score. IGFBP-1 could thus be used as a sensitive predictive diagnostic tool for obesity and its subsequent effects in screening and monitoring of obesity-related metabolic complications in adolescents.

BACKGROUND: Manufacturing costs, along with operational performance, are among the major factors determining the selection of the propulsion system for unmanned aerial vehicles (UAVs), especially for aerial targets and cruise missiles. OBJECTIVES: In this paper, the design requirements and operating parameters of small turbofan engines for single-use and reusable UAVs are analysed to introduce alternative materials and technologies for manufacturing their compressor blades, such as sintered titanium, a new generation of aluminium and an alloy based on titanium aluminides. METHODS: To assess the influence of severe plastic deformation (SPD) on the hardening efficiency of the proposed materials, the alloys in the coarse-grained and submicrocrystalline states were studied. Changes in physical and mechanical properties of materials were taken into account. The thermodynamic analysis of the compressor was performed in a finite element analysis system (ANSYS) to determine the impact of gas pressure and temperature on the aerodynamic surfaces of compressor blades of all stages. RESULTS: Based on thermal and structural analysis, the stress and temperature maps on compressor blades and vanes were obtained, taking into account the physical and mechanical properties of advanced materials and technologies of their processing. The safety factors of the components were established based on the assessment of their stress-strength reliability. Thanks to nomograms, the possibility of using the new materials and the technologies was confirmed in view of the permissible operating temperature and safety factors of blades. CONCLUSIONS: The proposed alternative materials and production technologies for the compressor blades and vanes meet the design requirements of the turbofan at lower manufacturing costs.

FoxP3 is a transcription factor essential for the differentiation and function of T regulatory cells (Tregs). There are two major subsets of Tregs: natural Tregs (nTregs) generated in thymus and inducible Tregs (iTregs) produced in peripheral immune system. It has been documented that iTreg development is dependent on soluble mediators including interleukin 2 (IL2), transforming growth factor β (TGFβ) and all-trans-retinoic acid (ATRA). In our experiments we performed a gene expression array, followed by Real-time PCR experiments, to study the expression of genes regulated by 1,25-dihydroxyvitamin D (1,25D) or ATRA in cells of myeloid origin. Our experiments revealed that ATRA alone, but also a cocktail of mediators consisting of IL2, TGFβ and ATRA, upregulate the expression of FOXP3 gene in lymphoid cells, but also in normal and leukemic myeloid cells. The FoxP3 expression is followed by a phenotypic changes in cells of myeloid origin. Our results indicate that signaling pathways which are used in the late stages of T cell differentiation, are also active in the cells of myeloid lineage

This paper gives a new unified formula for the Newtonian fluids valid for all pipe flow regimes from laminar to the fully rough turbulent. It includes laminar, unstable sharp jump from laminar to turbulent, and all types of the turbulent regimes: smooth turbulent regime, partial non-fully developed turbulent and fully developed rough turbulent regime. The formula follows the inflectional form of curves as suggested in Nikuradse’s experiment rather than monotonic shape proposed by Colebrook and White. The composition of the proposed unified formula consists of switching functions and of the interchangeable formulas for laminar, smooth turbulent and fully rough turbulent flow. The proposed switching functions provide a smooth and a computationally cheap transition among hydraulic regimes. Thus, the here presented formulation represents a coherent hydraulic model suitable for engineering use. The model is compared to existing literature models, and shows smooth and computationally cheap transitions among hydraulic regimes.

The beating heart is subject to intrinsic mechanical factors, exerted by contraction of the myocardium (stretch and strain) and fluid forces of the enclosed blood (wall shear stress). The earliest contractions of the heart occur already in the 10-somite stage in the tubular as yet unsegmented heart. With development the looping heart becomes asymmetric providing varying diameters and curvatures resulting in unequal flow profiles. These flow profiles exert various wall shear stresses and as a consequence different expression patterns of shear responsive genes. In this paper we investigate the morphological changes of the heart after changes the blood flow by ligation of the right vitelline vein in a model chicken embryo and analyze the extended expression in the endocardial cushions of the shear responsive gene Tgfbeta receptor III. A major phenomenon is the diminished endocardial-mesenchymal transition resulting in hypoplastic (even absence of) atrioventricular and outflow tract endocardial cushions, that might be lethal in early phases. The surviving embryos exhibit several cardiac malformations including ventricular septal defects and malformed semilunar valves related to a malposition of the aortopulmonary septum and the enclosed neural crest cells. We discuss the results in the light of the interactions between several shear stress responsive signaling pathways including Vegf, Notch, Pdgf, Klf2, eNos, Endothelin and Tgfβ/Bmp/Smad.

This research paper focuses on the synthesis and characterization of Cu-doped Mg-Co ferrites with varying compositions (Mg_0.6-xCo_0.4Cu_xFe₂O₄, where x = 0.0, 0.1, 0.2, and 0.3) using a solid-state reaction method. This paper also investigates the structural, morphological, magnetic, and electrical characteristics of synthesized Mg_0.6-xCo_0.4Cu_xFe₂O₄, where x = 0.0, 0.1, 0.2, and 0.3. The X-ray diffraction (XRD) technique confirms the ferrites spinel structure in the Fd-3m space group, with average crystallite sizes ranging from 57.29 to 48.57 nm. Fourier Transform Infrared (FTIR) spectroscopy verifies chemical and structural changes, while scanning electron microscopy (SEM) reveals cubic crystal growth with an average grain size of 1 to 1.5 μm. DC electrical resistivity decreases with increasing temperature and Cu²⁺ substitution, ranging from 1.4 x 10⁶ Ω-cm to 6.7 x 10⁵ Ω-cm. The study suggests a correlation between resistivity and Cu²⁺ concentration. Magnetic behaviour, studied using a Vibrating Sample Magnetometer (VSM), shows dependence on dopant concentration, with coercivity ranging from 157 Oe to 256 Oe. The results indicate potential applications in magnetic storage devices, antennas, transformers, and high-frequency electronics.

The mushroom industry generates large amounts of stems, a co-product with valuable sensory and health characteristics. This work aimed to study the influence of particle size (L — &gt;0.510 mm; LI — 0.510-0.315 mm; SI—0.315-0.180 mm; S — &lt;0.180 mm) and species in the characterization and antioxidant activity of flours from stems of Agaricus bisporus (ABSF) and Pleurotus ostreatus (POSF). ABSF was rich in protein (14 g/100 g), calcium (428.23-700.77 mg/100 g), and sorbitol (22.57-26.60 g/100 g), while POSF in β-glucans (36.62-40.34 g/100 g) and linoleic acid (20.57-39.86 g/100 g of lipid). Both species were flush in amino acids with umami flavor. The highest hydration properties and oil holding capacity were exhibited in the S size of both species. ABSF showed elevated values for emulsifying activity than POSF. ABSF-S recorded the heightened antioxidant capacity in vitro, in consonance with the total phenolic compounds (0.91 mg/g). However, this antioxidant assays in POSF presented a positive correlation with β-glucans content. According to these results, there could be several food applications for these co-products, such as emulsifier stabilizer, sweetener or fortifier in the development of functional food.

This study examined the patterns of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) deposition in the small intestine and colon to evaluate the association between histopathological severity of EFEMP1 deposition and constipation and determine if amyloid transthyretin (ATTR) and EFEMP1 deposits can colocalize. In 40 older cases (≥80 years of age), EFEMP1 deposition in the small intestine initiated in the submucosal and subserous vessels, subserous interstitium, and serosa (early stage); progressing to the muscularis propria and peri-Auerbach plexus area (intermediate stage); and finally, spreading diffusely to areas, excluding the mucosa and muscularis mucosa (advanced stage). The colon had a similar pattern of progression. During the middle-to-advanced stages, amyloid formation was observed in some vascular and serous deposits. We identified a subgroup of cases in which EFEMP1 deposition was the only presumed cause of constipation. Additionally, we demonstrated the colocalization of ATTR and EFEMP1 deposition. Apple-green birefringence was detected under polarized light only in approximately one-half of the cases in the small intestine and one-third of the cases in the colon. These findings emphasize that EFEMP1 deposits may be associated with lower gastrointestinal pathological conditions. Given the challenges of histopathological diagnosis on Congo red-stained specimens, we recommend the combined use of elastic fiber staining and immunohistochemistry for EFEMP1 to prevent overlooking this deposition.

Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Seventeen eyes with PNV that underwent half-fluence PDT with adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9–18 mm from the fovea. The <9- and 9–18-mm subfields were divided into four quadrants. Choroidal thickness in each subfield decreased significantly after half-fluence PDT (P<0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9x9-mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. In conclusion, half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

With the economic recession and the deterioration of the ecological environment becoming more and more prominent in the world, the sustainable operation of enterprises is facing the most difficult choice in history. For each responsible enterprise, it is crucial to choose the market power expansive strategy that can improve the realistic viability or the technological innovation strategy that can improve the future development potential. This is of great significance to reduce the negative external effects of the corporate social environment and ensure their sustainable development. In this paper, we select the data of 18 large listed petrochemical companies from 2003 to 2018 as samples and construct a linear regression model for empirical analysis. Meanwhile, we put forward more practical business management strategies for the sustainable development of petrochemical enterprises in developing countries in further research.

Cornelian cherry (Cornus mas L.) fruits, abundant in iridoids and anthocyanins, are natural products with proven beneficial impact on the functions of the cardiovascular system and the liver. The aim of this study is to stipulate and compare whether and to what extent two different doses of resin-purified cornelian cherry extract (10 mg/kg b.w. or 50 mg/kg b.w.) applied in a cholesterol-rich diet rabbit model affect the levels of ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, CCAAT/enhancer binding protein α, sterol regulatory ele-ment-binding protein 1c, fatty acid synthase, endothelial lipase, carnitine palmitoyltransferase 1A, and adiponectin receptor 2 in liver tissue; lipoprotein lipase, visceral adipose tissue-derived serine protease inhibitor, and retinol-binding protein 4 in visceral adipose tissue; resistive index of com-mon carotid arteries and aortas, and histopathological changes in CCAs. Obtained outcomes are referred to the results of our previous works. Moreover, our study, to our knowledge, test the in-fluence of Cornus derivative on CPT1A, AdipoR2, RBP4, LIPG, and vaspin for the first time, with a relevant outcome for the first three. Oral administration of the cornelian cherry extract decreased the SREBP-1c and C/EBPα in both doses. The dose of 10 mg/kg b.w. increased ABCA1 and de-creased FAS, CPT1A, and RBP4, and the dose of 50 mg/kg b.w. enhanced ABCG1 and AdipoR2. Mitigation in atheromatous changes in rabbits’ CCAs was also observed. The beneficial results confirm that cornelian cherry fruit extract may constitute a potentially effective product in the prevention and treatment of obesity-related disorders.

This paper conducts an extensive literature review focusing on the utilisation of crack tip plasticity as a crucial parameter in determining and enhancing crack growth models. The review encompasses a comprehensive analysis of various methodologies, predominantly emphasising numerical simulations of crack growth models while also considering analytical approaches. Although experimental investigations are not the focus of this review, their relevance and interplay with numerical and analytical methods are acknowledged. The paper critically examines these methodologies, providing insights into their advantages and limitations. Ultimately, this review aims to offer a holistic understanding of the role of crack tip plasticity in the development of effective crack growth models, highlighting the synergies and gaps between theoretical, experimental, and simulation-based approaches.