Microbe bioengineering has the potential to improve the nutritional value and health benefits of food products. Modifying microbial cells to produce specific proteins or compounds that can improve human health is one approach. Penicillin and recombinant insulin are two examples of this. The production of recombinant insulin by genetically modified E. coli bacteria has transformed diabetes treatment by providing a consistent and cost-effective source of insulin. Previously, insulin was extracted from the pancreas of animals, which was an expensive process that frequently resulted in impurities that could cause adverse reactions. Bioengineered insulin is now the standard diabetes treatment, providing a safe and effective method of controlling blood glucose levels. Bacteria, for example, can be genetically modified to produce vitamins like B12, which are difficult to obtain from plant sources. Likewise, yeasts can be genetically modified to produce β-carotene, a precursor to vitamin A that is required for vision, immune function, and skin health. Overall, bioengineered microorganisms have the potential to provide significant health benefits by producing essential compounds and proteins. Because of ongoing advances in genetic engineering techniques and understanding microbial metabolism, the possibilities for improving human health through bioengineering are limitless.

The JC polyomavirus virus (JCPyV) affects more than 80% of the human population in their early life stage. It mainly affects immunocompromised individuals where virus replication in oligodendrocytes and astrocytes may lead to fatal progressive multifocal encephalopathy (PML). Virus protein 1 (VP1) is one of the major structural proteins of the viral capsid, responsible for keeping the virus alive in the gastrointestinal and urinary tracts. VP1 is often targeted for antiviral drug and vaccine development. Similarly, this study implied immunoinformatics and molecular dynamics simulation-based approaches to design a multi-epitope subunit vaccine targeting JCPyV. The VP1 protein epitopic sequences, which are highly conserved, were used to build the vaccine. This designed vaccine includes two adjuvants, five HTL epitopes, six CTL epitopes, and two linear BCL epitopes to stimulate cellular, humoral, and innate immune responses against JCPyV. Furthermore, molecular docking and molecular dynamics simulation (100ns) studies were used to examine the interaction and stability of the vaccine protein with TLR4. Trajectory analysis showed that the vaccine and TLR4 receptor form a stable complex with the vaccine protein. Overall, this study contributed to the path of vaccine development against JCPyV and may prevent PML from happening. However, this study needs experimental validation to conclude our findings.

This study aimed to develop chitosan-based apigenin spray dried solid dispersion using 1:1,1:1.5,1:2 w/w ratios. The results of process yield and drug assay were found to be (87.5%, 94.2%, and 95.86%), (95.2 ±1.34%), (99.5 ±0.85%), and (97.6 ±2.42%), respectively, for AC1, AC2, and AC3. Flow properties indicate the free flow of powders. FTIR revealed compatibility among chitosan and apigenin, and DSC and XRD showed prepared solid dispersion was on a molecular level and available in amorphous. In contrast, SEM images reflect irregular block and near-spherical shape elongated particles in the selected AC2. The antimicrobial examination reflects that AC2 was more effective against Gram-positive, negative, and fungal strains. AC2 SDSDs has more anti-oxidant property compared to pure flavonoid (AGN). Anti-proliferative activity against A549 lung cancer cell lines showed better anti-cancer activity by AC2 SDSDs. The selected AC2 SDSD filled in a 3D shell pill and further characterized for 3D shell pill for dissolution profiles and stability studies. The product has sustained release and similar release profiles after three months of storage. The findings suggest that the AC2 SDSDs may be a promising candidate for further development as a 3D printed drug delivery system for treating multiple disease conditions using model flavonoid- apigenin.

Multi-disciplinary archaeological investigations have been conducted since 2006 at the Pattanam coastal village of Ernakulam District in Kerala. The archaeological investigations have confirmed that Pattanam is an integral part of the legendary port of Muziris aka Muciri Pattinam, which played an important role in the transoceanic exchanges between 100 BCE and 300 CE. So far the material evidence with direct provenance to the maritime exchange related to ancient migrations like Romans, Jews, traders of the Middle East and Catholics have been identified at Pattanam. However, the genetic evidence supporting the impact of multiple cultures or their admixing is still missing for this important archaeological site of South India. Hence, in the current study, we made the first attempt to infer the genetic composition of the skeletal remains excavated from the site in a broader context of South Asian and worldwide maternal affinity. We applied the MassArray-based genotyping approach of mitochondrial makers and observed that ancient samples of Pattanam represent a mixed ancestry pattern as both the West Eurasian ancestry and the South Asian ancestry can be seen in the final analysis. A high occurrence of West Eurasian (T, JT and HV) haplogroups and South Asian-specific mitochondrial haplogroups (M2a, M3a, R5 and M6) was found. The findings are consistent with the previously published archaeological findings, in which a mixture of multiple cultural and linguistic groups migrated, settled, and eventually died on the Southwestern coast of India.

Objective: Determine the feasibility of utilizing longitudinal electronic dental record (EDR) data to track change over time in patient periodontal disease (PD) and to generate three patient cohorts: 1) patients whose disease did not change over time, 2) patients whose PD progressed, and 3) patients whose disease improved over time using informatics approaches. Methods: We conducted a retrospective study of 28,908 patients who received a comprehensive oral evaluation between January 1, 2009, and December 31, 2014, at the Indiana University School of Dentistry (IUSD) clinics. We developed and tested three automated computer applications to: 1) diagnose periodontitis cases from periodontal charting, 2) retrieve clinician-documented diagnoses from clinical notes, and 3) track disease change over time. We also evaluated the density of longi-tudinal EDR data for the following follow-up times: 1) none, 2) up to 5 years, 3) >5 and <=10 years, and 4) >10 and <=15 years Results: Thirty-four percent (n=9,954) of the study cohort had up to five years of follow-up visits with an average of 2.78 visits with periodontal charting information. An average of three patient visits per year that contained periodontal charts (63,552) were utilized to obtain a diagnosis, which is considered excellent. For clinician-documented diagnoses from clinical notes, 42% of patients (n=5,562) had at least two PD diagnoses to determine their disease change. In this cohort with cli-nician-documented diagnoses, 72% percent of patients (n=3,919) did not have a disease status change between their first and last visits, 669 (13%) patients' disease status progressed, and 589 (11%) patients’ disease improved. Conclusions: This study demonstrated the feasibility of utilizing longitudinal EDR data to track disease changes over 15 years during the observation study period. We found excellent longitudinal data when diagnoses generated from periodontal charting were considered (three visits per pa-tient). This information can be now utilized for studying the clinical course of periodontitis.

Abstract: Background: Surgery on varicose veins (crossectomy and stripping) leads to recurrence and has clinical and socio-economic repercussions. Their etiopathogenesis has yet to fully under-stood. Objective: Study the expression of endoglin and other molecules involved in the neovascu-larisation process in patients suffering from this disease. Methods: 43 patients that have undergone surgery for varicose veins (24 primary and 19 recurrent). They were identified on the venous wall (proximal -saphenofemoral junction- and distal), via real-time RT-PCR, and in serum, via ELISA: Endoglin (Eng), Vascular Endothelial Growth Factor (VEGF-A), its receptors 1 and 2 (VEGFR1 or FLT1), (VEGFR2 or FLK), and the Hypoxia-Inducible Factor (HIF-1A). All the patients signed a con-sent form. Results: The recurrent group recorded a higher expression of Eng, VEGF-A, VEGFR1 and VEGFR2 at the level of proximal venous wall compared to the primary group. HIF-1A did not record any differences. As regards the determination of the distal venous wall, no markers recorded differ-ences between the groups. Among the serum determinations, only sFLT1 recorded a significant drop among the patients with recurrent varicose veins. Conclusions: Patients with recurrent vari-cose veins record a higher expression of endoglin and other markers of angiogenesis in proximal veins. Endoglin in the blood (sEng) has not proven to be of any use in recurrent varicose veins.

Uncontrolled transmission of Mycobacterium tuberculosis (M. tuberculosis, MTB) drug resistant strains is a challenge to control efforts of global tuberculosis programme. Due to increasing multi-drug resistant (MDR) cases in Arunachal Pradesh, a northeastern state of India, the tracking and tracing of these resistant MTB strains is crucial for infection control and spread of drug resistance. This study aims to correlate the phenotypic DST, genomic DST (gDST) and phylogenetic analysis of MDR-MTB strains in the region. Of total 200 suspected MDR-MTB isolates, 125(62.5%) were identified as MTB. MGIT-960 SIRE DST detected 71/125(56.8%) isolates as MDR/RR-MTB of which 22(30.9%) were detected resistant to second line drugs. Whole genome sequencing of 65 isolates and their gDST found Ser315Thr mutation in katG (35/45;77.8%) and Ser531Leu mutation in rpoB (21/41;51.2%) associated with drug resistance. SNP barcoding categorized the dataset with Lineage2 (41;63.1%) being predominant followed by Lineage3 (10;15.4%), Lineage1 (8;12.3%) and Lineage4 (6;9.2%) respectively. Phylogenetic assignment by cgMLST gave insights of two Beijing sub-lineages viz; 2.2.1 (SNP difference &lt; 19) and 2.2.1.2 (SNP difference &lt; 9) associated with recent ongoing transmission in Arunachal Pradesh. This study provides first insight in identifying the ongoing transmission of two virulent Beijing sub-lineages associated with TB drug resistance.

Epilepsy is a heterogenous neurological disorder characterized by recurrent unprovoked seizures, mitochondrial stress, and neurodegeneration. Hydrogen sulfide (H2S), a gasotransmitter, promotes mitochondrial function and biogenesis, elicits neuromodulation and neuroprotection, and may acutely suppress seizures. A major gap in knowledge remains in understanding the role of mitochondrial dysfunction and progressive changes in H2S levels following acute seizures and during epileptogenesis. We thus sought to quantify changes in H2S and its methylated metabolite (MeSH) via LC-MS/MS subsequent to acute maximal electroshock and 6 Hz 44 mA seizures in mice, as well as in the corneal kindled mouse model of chronic seizures. Plasma H2S was acutely reduced after a maximal electroshock seizure. H2S or MeSH levels in whole brain homogenate and expression of related genes in corneal kindled mice were not altered. However, plasma H2S and MeSH levels were significantly lower during kindling, but not after established kindling. Morever, we demonstrated a time-dependent increase in expression of mitochondrial membrane integrity-related proteins, Opa1, Mfn2, Drp1, and Mff during kindling, which did not correlate with gene expression. Taken together, short-term reductions in plasma H2S could be a novel biomarker for seizures. Future studies should further define the role of H2S and mitochondrial stress in epilepsy.

Quantum turbulence is characterized by many degrees of freedom interacting non-linearly to produce disordered states, both in space and time. The advances in trapping, cooling, and tuning the interparticle interactions in atomic Bose-Einstein condensates (BECs) make them excellent candidates for studying quantum turbulence. In this work, we investigate the decaying regime of quantum turbulence in a trapped BEC. Although much progress has been made in understanding quantum turbulence, other strategies are needed to overcome some intrinsic difficulties. We present an alternative way of investigating this phenomenon by defining and computing a characteristic length scale, which possesses relevant characteristics to study the establishment of the quantum turbulent regime. One intrinsic difficulty related to these systems is that absorption images of BECs are projected to a plane, thus eliminating some of the information present in the original momentum distribution. We overcome this difficulty by exploring the symmetry of the cloud, which allows us to reconstruct the three-dimensional momentum distributions with the inverse Abel transform. We present our analysis with both the two- and three-dimensional momentum distributions, discussing their similarities and differences. We argue that the characteristic length allows us to visualize the time evolution of the turbulent state intuitively.

In this work, we derive the spectral efficiency, secrecy outage probability, and bit error rate of a communication system assisted by a large intelligent surface (LIS). We consider a single-antenna user and an array of antennas at the transmitter side and the possibility of a direct link between transmitter and receiver. Additionally, there is a single-antenna eavesdropper with a direct link to the transmitter, which is modeled as a Nakagami-m distributed fading coefficient. The channels from transmitter to the LIS and from the LIS to the user may or may not have the line-of-sight (LoS) and are modeled by the Nakagami- m distribution. Moreover, we assume that the LIS elements perform non-ideal phase cancellation leading to a residual phase error that assumes a Von Mises distribution. We show that the resulting channel can be accurately approximated by a Gamma distribution whose parameters are analytically estimated using the moments of the equivalent signal-to-noise ratio. We also provide an upper bound for the error probability for M-QAM modulations. With the derived formulas, we analyze the effect of the strength of the LoS link by varying the Nakagami parameter, m.

This paper presents an analysis of future precipitation patterns over the Lake Victoria Basin using bias-corrected CMIP6 model projections. A mean increase of about 5% in mean annual (ANN) and seasonal [March-May (MAM), June-August (JJA), and October-December (OND)] precipitation climatology is expected over the domain by mid-century (2040-2069). The changes intensify towards the end of the century (2070-2099) with an increase in mean precipitation of about 16% (ANN), 10% (MAM), and 18% (OND) expected, relative to the 1985-2014 baseline period. Additionally, the mean daily precipitation intensity (SDII), the maximum 5-day precipitation values (RX5Day), and the heavy precipitation events, represented by the width of the right tail distribution of precipitation (99p-90p) show an increase of 16%, 29%, and 47%, respectively, by the end of the century. The projected changes have a substantial implication for the region - which is already experiencing conflicts over water and water-related resources.

The innovation of the new psychoactive substances (NPS) market requires the rapid identification of new substances that can be a risk to public health, in order to reduce the damage due to their use. Twelve seized products suspected to contain illicit substances were analyzed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), gas chromatography coupled to mass spectrometry (GC-MS), and nuclear magnetic resonance spectroscopy (NMR). Synthetic cathinones (SCat) were found in all products, either as a single component or in mixtures. Infrared spectra of all products were consistent with the molecular structure of SCat, showing an intense absorption band at 1700–1674 cm‐1, corresponding to the carbonyl stretching, a medium/strong peak at 1605-1580 cm-1, indicating stretching vibrations in the aromatic ring (C=C) and bands with relative low intensity at frequencies near 2700–2400 cm-1, corresponding to an amine salt. It was possible to identify a total of eight cathinone derivatives by GC-MS and NMR analysis: 4’-methyl-α-pyrrolidinohexanophenone (MPHP), α-pyrrolidinohexanophenone (α-PHP), 3-fluoromethcathinone (3-FMC), methedrone, methylone, buphedrone, N-ethylcathinone, and pentedrone. Among the adulterants found in these samples, caffeine was the most frequently detected substance, followed by ethylphenidate. These results highlight the prevalence of SCat in seized materials of the Portuguese market. Reference standards are usually required for confirmation, but when reference materials are not available, the combination of complementary techniques is fundamental for a rapid and an unequivocal identification of such substances.

Large intelligent surfaces (LIS) promises not only to improve the signal to noise ratio, and spectral efficiency but also to reduce the energy consumption during the transmission. We consider a base station equipped with an antenna array using the maximum ratio transmission (MRT), and a large reflector array sending signals to a single user. Each subchannel is affected by the Rayleigh flat fading, and the reflecting elements perform non-perfect phase correction which introduces a Von Mises distributed phase error. Based on the central limit theorem (CLT), we conclude that the overall channel has an equivalent Gamma fading whose parameters are derived from the moments of the channel fading between the antenna array and LIS, and also from the LIS to the single user. Assuming that the equivalent channel can be modeled as a Gamma distribution, we propose very accurate closed-form expressions for the bit error probability and a very tight upper bound. For the case where the LIS is not able to perform perfect phase cancellation, that is, under phase errors, it is possible to analyze the system performance considering the analytical approximations and the simulated results obtained using the well known Monte Carlo method. The analytical expressions for the parameters of the Gamma distribution are very difficult to be obtained due to the complexity of the nonlinear transformations of random variables with non-zero mean and correlated terms. Even with perfect phase cancellation, all the fading coefficients are complex due to the link between the user and the base station that is not neglected in this paper.

In this study, a novel task of printing speed optimization for continuous fiber composites is investigated. Using continuous fibers is an innovative approach to reinforce products made by fused filament fabrication (FFF) additive manufacturing (AM) technology. In the printing process of composites with continuous fibers, the printing speed is critical because of its significant effect on the geometric shape of the samples, especially their corners. During optimization in this research, continuous glass fiber (CGF) and polylactic acid (PLA) filaments were utilized as reinforcing phase and matrix, respectively, and were simultaneously fed into the extrusion-based polymer 3D printer to form PLA/CGF composites. The optimization was carried out by calculating the temperature changes of the deposited rasters in the presence and absence of fibers as a first step and then determining the special relationship between the printing speeds and rasters temperature changes. Finally, the optimal and the maximum printing speed was computed based on a hypothesis, which is proved by the results of high-quality printed composites with different geometric shapes.

Agile methods promise to achieve high productivity and provide high-quality software. Agile software development is the most important approach that has spread through the world of software development over the past decade. Software team productivity measurement is essential in agile teams to increase the performance of software development. Due to the prevalence of agile methodologies and increasing competition of software development companies, software team productivity has become one of the crucial challenges for agile software companies and teams. Awareness of the level of team productivity can help them to achieve better estimation results on the time and cost of the projects. However, to measure software productivity, there is no definitive solution or approach whether in traditional and agile software development teams that lead to the occurrence of many problems in achieving a reliable definition of software productivity. Hence, this study aims to propose a statistical model to assess the team’s productivity in agile teams. A survey was conducted with forty software companies and measured the impact of six factors of the team on productivity in these companies. The results show that team effectiveness factors including inter-team relationship, quality conformance by the team, team vision, team leader, and requirements handled by the team had a significant impact on the team’s productivity. Moreover, the results also state that inter-team relations affect the most on software teams’ productivity. Finally, the model fit test showed that 80% of productivity depends on team effectiveness factors.

In the application of classical nucleation theory (CNT) and all other theoretical models of crystallization of liquids and glasses it is always assumed that nucleation proceeds only after the supercooled liquid or the glass have completed structural relaxation processes towards the metastable equilibrium state. Only employing such assumption, the thermodynamic driving force of crystallization and the surface tension can be determined in the way it is commonly performed. The present paper is devoted to the theoretical treatment of a different situation when nucleation proceeds concomitantly with structural relaxation. To treat the nucleation kinetics theoretically for such cases, we need adequate expressions for the thermodynamic driving force and the surface tension accounting for the contributions caused by the deviation of the supercooled liquid from metastable equilibrium. In the present paper, such relations are derived. They are expressed via deviations of structural order parameters from their equilibrium values. Relaxation processes result in changes of the structural order parameters with time. As a consequence, the thermodynamic driving force and surface tension, and basic characteristics of crystal nucleation, such as the work of critical cluster formation and the steady-state nucleation rate, also become time-dependent. We show that this scenario may be realized in the vicinity and below the glass transition temperature, and it may occur only if diffusion (controlling nucleation) and viscosity (controlling the alpha-relaxation process) in the liquid decouple. Analytical estimates are illustrated and confirmed by numerical computations for a model system. The theory is successfully applied to the interpretation of experimental data. Several further consequences of this newly developed theoretical treatment are discussed in detail. In line with our previous investigations, we reconfirm that only when the characteristic times of structural relaxation are of similar order of magnitude or longer than the characteristic times of crystal nucleation, elastic stresses evolving in nucleation may significantly affect this process. Completing the analysis of elastic stress effects, for the first time expressions are derived for the dependence of the surface tension of critical crystallites on elastic stresses. As the result, a comprehensive theoretical description of crystal nucleation accounting appropriately for the effects of deviations of the liquid from the metastable states and of relaxation on crystal nucleation of glass-forming liquids, including the effect of simultaneous stress evolution and stress relaxation on nucleation, is now available. As one if its applications, this theoretical treatment provides a new tool for the explanation of the low-temperature anomaly in nucleation in silicate and polymer glasses (the so-called \breakdown" of CNT at temperatures below the temperature of the maximum steady-state nucleation rate). We show that this anomaly results from much more complex features of crystal nucleation in glasses caused by deviations from metastable equilibrium (resulting in changes of the thermodynamic driving force, the surface tension, and the work of critical cluster formation, in the necessity to account of structural relaxation and stress effects) than assumed so far.

Blockchain technology has become one of the most popular technologies for maintaining digital transactions. From the foundation of Bitcoin to the now predominant smart contract, blockchain technology promises to induce a shift in thought about digital transactions in many fields, such as energy, healthcare, Internet of Things, cybersecurity, financial services and the supply chain. Despite blockchain technology offers many cryptography advantages such as immutability, digital signature and hashing; it has suffered from several critical cybersecurity threats and vulnerabilities. In this paper, we build upon the previous studies on vulnerabilities and investigates over 60 real cybersecurity incidents that have been happening on the blockchain networks between 2009 and 2019. We categorise those incidents against the key cybersecurity vulnerabilities in blockchain technologies; and have developed a taxonomy that captures five types of cybersecurity threats and vulnerabilities based on five main players in blockchain. The outcome of this research prompted concerns and research direction in developing countermeasures to alleviate these risks.

Considering citizens' perceptions of their living environment is very helpful in making the right decisions for city planners who intend to build a sustainable society. Mental map analyses are widely used in understanding the level of perception of individuals regarding the surrounding environment. The present study introduces Aram Mental Map Analyzer (AMMA), an open-source program, which allows researchers to use special features and new analytical methods to receive outputs in numerical data and analytical maps with greater accuracy and speed. AMMA performance is contingent upon two principles of accuracy and complexity, the accuracy of the program is measured by Accuracy Placed Landmarks (APL) and General Orientation (GO), which respectively analyses the landmark placement accuracy and the main route mapping accuracy. Also, the complexity section is examined through two analyses Cell Percentage (CP) and General Structure (GS), which calculates the complexity of citizens’ perception of space based on the criteria derived from previous studies. AMMA examines all the dimensions and features of the graphic maps, and its outputs have a wide range of valid and differentiated information, which is tailored to the research and information subject matter that is required.

Most of the municipalities in the Gulf region are facing performance related issues in their municipal solid waste management (MSWM) systems. They lack to possess a deliberate inter-municipality benchmarking processes. Instead of identifying the performance gaps for their key components (e.g., personnel productivity, operational reliability, etc.) and adopt proactive measures, the municipalities primarily rely on an efficient emergency response. A novel hierarchical modeling framework, based on deductive reasoning, is developed for performance assessment of MSWM systems. Fuzzy rule based modeling using Simulink-MATLAB was used for performance inferencing at different levels, i.e., component, sub-components, etc. The model is capable of handling the inherent uncertainties due to limited data and imprecise knowledge base. The model’s outcomes can exclusively assist the managers working at different levels of organizational hierarchy for effective decision-making. Performance of the key component, assists the senior management to assess the overall compliance level of performance objectives. Subsequently, operation management can hone in the sub-components to acquire useful information for intra-municipality performance management. While, individual indicators are useful for inter-municipality benchmarking. The model has been implemented on two municipalities operating in Qassim Region, Saudi Arabia. The results demonstrate the model’s pragmatism for continuous performance improvement of MSWM systems in the country and elsewhere.

Cost-effective and functionalized scaffolds are in high demand for stem-cell-based regenerative medicine to treat refractory bone defects in craniofacial abnormalities and injuries. One potential strategy is to utilize pharmacological and cost-effective plant polyphenols and biocompatible proteins, such as gelatin. Nevertheless, the use of chemically modified proteins with plant polyphenols in this strategy has not been standardized. Here, we demonstrated that gelatin chemically modified with epigallocatechin gallate (EGCG), the major catechin isolated from green tea, can be a useful material for dedifferentiated fat cells and adipose-derived stem cells and can induce bone regeneration in a rat congenial cleft-jaw model in vivo. Vacuum-heated gelatin sponge modified with EGCG (vhEGCG-GS) induced superior osteogenesis from these two cell types compared with vacuum-heated gelatin sponge (vhGS). The EGCG-modification converted the water wettability of vhGS to a hydrophilic property (contact angle: 110° to 3.8°) and the zeta potential to a negative surface charge; the modification enhanced the cell adhesion property and promoted calcium phosphate precipitation. These results suggest that the EGCG-modification with chemical synthesis can be a useful platform to modify the physicochemical property of gelatin. This alteration is likely to provide a preferable microenvironment for multipotent progenitor cells, inducing superior bone formation in vivo.

Adenosine to inosine (A-to-I) RNA editing is a highly conserved regulatory process carried out by adenosine-deaminases (ADARs) on dsRNAs. Although a considerable fraction of the transcriptome is edited, the function of most editing sites is unknown. Previous studies indicate changes in A-to-I RNA editing frequencies following exposure to several stress types. However, the overall effect of stress on the expression of ADAR targets is not fully understood. Here, we performed high-throughput RNA sequencing of wild-type and ADAR mutant C. elegans worms after heat-shock to analyze the effect of heat-shock stress on the expression pattern of genes. We found that ADAR regulation following heat-shock does not directly involve heat-shock related genes. Our analysis also revealed that lncRNAs and pseudogenes, which have a tendency for secondary RNA structures, are enriched among upregulated genes following heat-shock in ADAR mutant worms. The same group of genes is downregulated in ADAR mutant worms under permissive conditions, which is likely, considering that A-to-I editing protects endogenous dsRNA from RNA-interference (RNAi). Therefore, temperature increases may destabilize dsRNA structures and protect them from RNAi degradation, despite the lack of ADAR function. These findings shed new light on the dynamics of gene expression under heat-shock in relation to ADAR function.

In this work we demonstrate the proof-of-concept of real-time discrimination between patches of serine or isoleucine monomers in the primary structure of custom-engineered, macro-dipole-like peptides, at uni-molecular level. We employed single-molecule recordings to examine the ionic current through the α-hemolysin (α-HL) nanopore, when hydrophilic serine or hydrophobic isoleucine residues, flanked by segments of oppositely charged arginine and glutamic amino acids functioning as a voltage-dependent ‘molecular brake’ on the peptide, were driven at controllable rates across the nanopore. The observed differences in the ionic currents blockades through the nanopore, visible at time resolutions corresponding to peptide threading through the α-HL’s constriction region, was explained by a simple model of the volumes of electrolyte excluded by either amino acid species, as groups of three serine or isoleucine monomers transiently occupy the α-HL. To provide insights into the conditions ensuring optimal throughput of peptide readout through the nanopore, we probed the sidedness-dependence of peptide association to and dissociation from the electrically and geometrically asymmetric α-HL.

Thermoelectric materials may be used in devices as thermoelectric “air conditioner” in a smart house for improved energy efficiency. Energy harvesting uses ambient energy to generate electricity. It provides potentially low-cost, maintenance-free, long-life equipment by reducing the need for batteries or power chords. Energy harvesting (EH) is also known as power harvesting or energy scavenging. EH is considered to give benefits related to environmental friendliness, safety, security, convenience and affordability. EH can be used for brand enhancing. Technically, it can be used to make new things possible depending on visionary engineering. The variety of thermoelectric (TE) materials that can be used in energy harvesting is quite large, and the optimal material for a given application depends mainly on the temperature range in which the material is to be used. In this work we study the development and characterization of thermoelectric materials which were prepared by two different method, which were: a) ball-milling followed by sintering and b) ball-milling, microwave synthesis, high energy planetary ball milling, and sintering. Finally, we study the thermoelectric properties, calculate the band gaps and the ZT for the thermoelectric materials.

Crystal structures of simple metals and binary alloy phases based on the face-centered cubic (fcc) structure are analyzed within the model of Fermi sphere – Brillouin zone interactions to understand the stability of original cubic structure and derivative structures with distortions, superlattices and vacancies. Examination of the Brillouin-Jones configuration in relation to the nearly-free electron Fermi sphere for several representative phases reveals significance of the electron energy contribution to the phase stability. Representation of complex structures in the reciprocal space clarifies their relationship to the basic cubic cell.

In this project, four of fibers Bragg gratings were fabricated by injecting different volumes of liquids (star line Glass Mechanix optical adhesive material, olive oil diluted with ethanol) into the hollow core fiber. The amplitude splitting interferometric technique with a high resolution specially designed translation stage was used for the fabrication process. The fabrication was done using ultraviolet laser operated at wavelength 405nm. The fabricated Bragg length of the four fibers is equal to 3.8 cm. The results presented fiber Bragg grating (FBG) with successful fabrication at 653.3 nm Bragg reflected wavelength.

Livestock production in the Cajamarca, La Libertad and Amazonas basins is based on pasture-based feeding with "Cajamarquino ecotype" ryegrass under monoculture or in association with white clover. The objective of this research work was the morphological characterization and evaluation of the productive yield and cutting time of annual ryegrass - Lolium multiflorum L. Six local genotypes of Lolium multiflorum in six locations were characterised, using the multiplicative interaction effect model and additive main effects for the analysis of interaction and variability of the genotypes and locations. Ryegrass “Cajamarquino ecotype” is semi-erect with intermediate growth, with a dark green colouring, 0.8 cm broadleaf, and can reach an average stem length of 46 cm, up to 1.6 cm.day, achieving the growth of the fourth leaf after 28 days under adequate management conditions. Despite the differentiated characteristics, according to the BLASTn evaluation, the ITS1 sequences showed an identification greater than 99.9% similar to Lolium multiflorum L. It was determined that the Cajamarquino ecotype produces from 3.52 to 4.98 Mg.ha.biomass cutting. Likewise, the pasture's quality is better when used at 30 days with 14.84% protein and at 45 days, it achieves 12.75% protein with a biomass of 4.05 Mg.ha.cut. With these morphological and yield characteristics, the "Cajamarca ecotype" ryegrass is a well-adapted species for local livestock farming. These species are adapted to the Sierra Norte area of Peru.

Background: Glioblastoma remains a challenging brain tumor to treat due to its infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful tumor resection. This study introduces an innovative intraoperative visualization method utilizing a surgical fluorescence microscope to precisely locate tumor cells. The focus of the study is on IR-Glint, a novel preparation comprising Cy7.5-labeled aptamers Gli-233nt and Gli-55_3L specific to human glioblastoma. Methods: The aptamers were modified using molecular modeling and quantum chemical techniques. The effectiveness of the preparation was assessed using flow cytometry and microscopy on primary cultures of human glioblastoma. In vivo studies were conducted on mouse and rabbit models, employing orthotopic xenotransplantation of human brain glioblastoma with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. Results: The experiments validated the potential of IR-Glint for intraoperative visualization of glioblastoma using infrared imaging. Surface application of the aptamer-based formulation on the brain allowed clear visualization of the tumor, aiding surgeons in tumor resection. This approach also reduces the dosage required and mitigates potential toxic effects on the patient. Conclusions: This study demonstrates the promising potential of using in-frared dye-labeled aptamers for intraoperative visualization of glioblastoma. By improving surgical treatment outcomes in neurosurgery, this novel approach may pave the way for future advancements in the field.

Global demand for food shows an increasing trend, which implies that volumes of food waste also increase. These wastes contain bioactive compounds that are not properly utilized or valorized. It was reported that ginger waste contains phenolic compounds with high antioxidant activity. Thus, this study aimed to evaluate the effect of temperature, time, and particle size on the total phenolic content (TPC) and antioxidant activity (AA) of ginger (Zingiber officinale R.) waste aqueous extract using the Pressurized Liquid Extraction (PLE) method with water as the sole solvent. Box-Behnken design was used. The sample was 1.60 kg of dried ginger peel powder. Data analysis was performed with Minitab ® 19.1 (64-bit). TPC ranged from 10.42 to 14.1 mg GAE/g, and AA (DPPH method) ranged from 72.9 to 111.9 μmol TE/g. The model explained 81.07% of AA’s total variability. Positive correlation was found between TPC and AA (Pearson's ρ = 0.58, p &lt; 0.05). Response optimization values were 126 °C and 38 min. Temperature was a significant factor (p &lt; 0.05) influencing AA, while time and particle size were not significant. Higher temperatures, longer extraction times and smaller particle sizes increase TPC and AA of the ginger waste aqueous extract.

The main objective of this study is to analyze the impact of investment in Research & Development on the performance and value of companies, that is, to try to explain how R&D investment influences the companies’ performance. For this purpose, a dynamic panel data model was estimated using the Generalized Method of Moments, which made possible to measure the impact of R&D investment on performance through the Return on Operating Assets ratio for the Portuguese companies that invested the most between 2012 to 2019. The results show that the investment in R&D is not statistically significant in explaining the operating return on assets. However, the lagged financial performance in one period, the leverage, the asset turnover ratio and the accounts payable turnover show to have impact on the variable under study.

This study empirically analyzes how R&D expenditures affect firm value using a regression model for listed firms in Shandong Province, China. The dependent variable is measured by To-bin Q, which measures firm value, and the experimental variable among the independent varia-bles is R&D expenditure. In addition, financial leverage and firm size, which have been found to have a significant impact on firm value in previous studies, were selected as control variables. The study sample consisted of 554 data points analyzed over a nine-year period from 2010 to 2018. Without controlling for variables that affect firm value, the correlation analysis shows that R&D expenditures of listed firms in Shandong Province, China have a significant positive impact on firm value at the 1% level. For a more precise analysis, we ran a multivariate regression analysis controlling for other variables that affect firm value and found that R&D expenditure has a significant positive impact on firm value at the 1% level. These findings suggest that man-agers of listed companies in Shandong Province, China, need to actively engage in R&D activi-ties to increase firm value. Companies in Shandong Province, China, are currently experiencing very strong growth, and this study, which shows that R&D is the key to increasing the value of these companies, can help companies in Shandong formulate their business strategies.

In this article we estimate the value of “Non-R&D Innovation Expenditures” in Europe. We use data from the European Innovation Scoreboard-EIS of the European Commission from the period 2010-2019. We test data with the following econometric models i.e.: Pooled OLS, Dynamic Panel, Panel Data with Fixed Effects, Panel Data with Random Effects, WLS. We found that “Non-R&D Innovation Expenditures” is positively associated among others to “Innovation Index” and “Firm Investments” and negatively associated among others to “Human Resources” and “Government Procurement of Advanced Technology Products”. We use the k-Means algorithm with either the Silhouette Coefficient and the Elbow Method in a confrontation with the network analysis optimized with the Distance of Manhattan and we find that the optimal number of clusters is four. Furthermore, we propose a confrontation among eight machine learning algorithms to predict the level of “Non-R&D Innovation Expenditures” either with Original Data-OD either with Augmented Data-AD. We found that Gradient Boost Trees Regression is the best predictor for OD while Tree Ensemble Regression is the best Predictor for AD. Finally, we verify that the prediction with AD is more efficient of that with OD with a reduction in the average value of statistical errors equal to 40,50%.

Stage of cancer is a discrete ordinal response that indicates aggressiveness of disease and is often used by physicians to determine the type and intensity of treatment to be administered. For example, the FIGO stage in cervical cancer is based on the size and depth of the tumor as well as the level of spread. It may be of clinical relevance to identify molecular features from high-throughput genomic assays that are associated with stage of cervical cancer, to elucidate pathways related to tumor aggressiveness, identify improved molecular features that may be useful for staging, and identify therapeutic targets. High-throughput RNA-Seq data and corresponding clinical data (including stage) for cervical cancer patients has been made available through The Cancer Genome Atlas Project (TCGA). We recently described penalized Bayesian ordinal response models that can be used for variable selection for over-parameterized datasets such as the TCGA-CESC dataset. Herein, we describe our ordinalbayes R package, available from the Comprehensive R Archive Network (CRAN), which is capable of fitting cumulative logit models when the outcome is ordinal and the number of predictors exceeds the sample size, P>N, such as for TCGA data. We demonstrate use of this package through application to TCGA cervical cancer dataset. Our ordinalbayes package can be used to fit models to high-dimensional dataset and effectively performs variable selection.

The study focuses on the application of R programming language towards marine geological research with a case study of Mariana Trench. Due to its logical and straightforward syntax, multi-functional standard libraries, R is especially attractive to the geologists for the scientific computing. Using R libraries, the unevenness of various factors affecting Mariana Trench geomorphic structure has been studied. These include sediment thickness, slope steepness, angle aspect, depth at the basement and magmatism of the nearby areas. Methods includes using following R libraries: {ggplot2} for regression analysis, Kernel density curves, compositional charts; {ggalt} for Dumbbell charts for data comparison by tectonic plates, ranking dot plots for correlation analysis; {vcd} for mosaic plots, silhouette plots for compositional similarities among the bathymetric profiles, association plots; {car} for ANOVA. Bathymetric GIS data processing was dome in QGIS and LaTeX. The innovativeness of the work consists in the multi-disciplinary approach combining GIS analysis and statistical methods of R which contributes towards studies of ocean trenches, aimed at geospatial analysis of big data.

Automated Electrocardiogram (ECG) processing is an important technique which helps in identifying abnormalities in the heart before any formal diagnosis. This research presents a real-time and lightweight R-assisted feature extraction algorithm and a heartbeat classification scheme which achieves highly accurate abnormality detection. In the proposed algorithm, we extract fifteen features from each heartbeat taken from raw Lead-II ECG signals. The features carry medically valuable information such as locations, amplitude and energy of ECG waves (P, Q, R, S, T waves) which are then used for detection of any abnormality that might be present in the heartbeat using various classification algorithms. We have used four popular databases from Physionet and extracted ten thousand ECG signals from each for training the models and benchmarking results. Four classification models i.e. Naïve Bays, k-Nearest Neighbor, Neural Network, Decision Tree were used for abnormality detection validating the efficiency of the system.

Telemedicine is the use of Information and Communication Technology (ICT) for clinical health care from a distance. The exchange of radiographic images and electronic patient health information/records (ePHI/R) for diagnostic purposes has the risk of confidentiality, ownership identity, and authenticity. In this paper, a data hiding technique for ePHI/R is proposed. The color information in the cover image is used for key generation, and stego-images are produced with ideal case. As a result, the whole stego-system is perfectly secure. This method includes the features of watermarking and steganography techniques. The method is applied to radiographic images. For the radiographic images, this method resembles watermarking, which is an ePHI/R data system. Experiments show promising results for the application of this method to radiographic images in ePHI/R for both transmission and storage purpose.

Purpose: The study investigates soil pores' impact on carbon dynamics and sequestration processes, examining their physical and chemical characteristics and their mechanisms for carbon sequestration.Research Method: Existing literature and research on soil pores, carbon dynamics, and carbon sequestration are analyzed. The interrelationships between soil pore structure, water movement, microbial activity, root penetration, carbon input, soil aggregation, and gas exchange are examined. Traditional techniques and advanced imaging methods are used to quantify and characterize soil pores.Findings: Soil pores play a critical role in facilitating carbon sequestration through various mechanisms. They affect water movement, microbial activity, root penetration, carbon input, soil aggregation, and gas exchange. Understanding these relationships is crucial for sustainable soil management.Research Limitations: This study relies on existing literature and research, which may have limitations and uncertainties. Further research is needed to address these gaps and enhance understanding.Originality Value: This research enhances the existing knowledge by comprehensively examining the significance of soil pores in carbon dynamics and sequestration. It incorporates both traditional and advanced methods, providing insights for soil management and contributing to climate change mitigation efforts.

Earth’s near space is a region between 20 and 100 km above sea level, which is characterized by low temperature, low atmospheric pressure, harsh radiation, and extreme dryness. These conditions are analogous to the surface of Mars and the atmosphere of Venus, and thus make it a unique natural lab for astrobiologists. To address the important astrobiological questions of the effects of the near space environmental conditions on biology and of the survival strategies of representative organisms in this planetary analog, teams from the Chinese Academy of Sciences have developed a scientific balloon platform named the Chinese Academy of Sciences Balloon-Borne Astrobiology Platform (CAS-BAP) and carried out a series of experiments in lower near space since 2019. Here, we describe the Biological Samples Exposure Payload (BIOSEP) loaded on CAS-BAP with respect to its structure and function. The primary role of BIOSEP is to expose biological/chemical samples to the planetary analog environments of Earth’s lower near space. Exposed samples will be returned to laboratories for morphological, physiological, chemical, and genetic analyses. The development of BIOSEP and associated biological exposure experiments will improve our understanding of the livelihood of potential Mars lives and the potential habitability of the atmosphere regions of other planets in the Solar System and beyond.

Surfactant proteins A and D (SP-A and SP-D) belong to the collectin subfamily of C-type oligomeric lectins. They are pattern-recognition molecules (PRM), able to recognise pathogen- or dan-ger-associated molecular patterns (PAMP, DAMP) in the presence of Ca2+ cations. That property enables opsonisation or agglutination of non-self or altered/abnormal self-cells, and contributes to their clearance. Like other collectins, SP-A and SP-D are characterised by the presence of four distinct domains: a cysteine-rich domain (at N-terminus), a collagen-like region, an α-helical neck domain and a globular carbohydrate-recognition domain (CRD) (at C-terminus). Pulmonary sur-factant is a lipoprotein complex, preventing alveolar collapse by reducing surface tension at the air-liquid interface. SP-A and SP-D, produced by type II alveolar epithelial cells, and Clara cells, are not only pattern-recognition molecules but also contribute to the surfactant structure and homeo-stasis. Moreover, they are expressed in a variety of extrapulmonary sites where they are involved in local immunity. The term “cancer” includes a variety of diseases: tumours start from uncontrolled growth of abnormal cells in any tissue which may further spread to other sites of the body. Many cancers are incurable, difficult to diagnose and often fatal. This short review summarises anti- and pro-tumourigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy.

Objective biomarkers have been a critical challenge for the field of psychiatry, where diagnostic, prognostic and theranostics assessments are still based on subjective narratives. Psychopathology operates with idiographic knowledge and subjective evaluations incorporated into clinical as-sessment inventories, but is considered to be a medical discipline and, as such, uses medical in-tervention methods (e.g., pharmacological, ECT; rTMS; tDCS), and therefore is supposed to oper-ate with the language and methods of nomothetic networks. The idiographic assessments are pro-visionally “quantified” into “structured clinical scales” to in some way resemble nomothetic measures. Instead of fostering data merging and integration, this approach further encapsulates the clinical psychiatric methods, as all other, biological tests (molecular, neuroimaging) are per-formed separately, only after the clinical assessment has provided diagnosis. Translational cross-validation of clinical assessment instruments and fMRI is an attempt to address the gap. The aim of this approach is to investigate whether there exist common and specific neural circuits, which underpin differential item responses to clinical self-rating scales during fMRI session in pa-tients suffering from the two main spectra of mental disorders: schizophrenia and major depres-sion. The current status of this research program and future implications to promote the devel-opment of psychiatry as a medical discipline are discussed.

This study investigates the petroleum potential of the Middle Jurassic Khatatba Formation (Fm) in the Matruh Basin, northwestern Egypt. This formation shows in situ dual source and reservoir characteristics, where alternations of fine and coarse clastics were deposited during semi-arid and semi-humid conditions due to climate changes and Tethyan sea level fluctuations. The organic-rich shales and argillaceous siltstones are fair to very good/excellent (TOCm wt%: 0.91–3.07) source rocks. They are rich in late mature to early postmature mostly gas-prone organic facies C, which sourced the juxtaposing intraformational coarse clastics of the Lower Safa Member with gas and condensates. The source rocks show poor to fair gas generation potential (S2: 0.38–1.96, mg HC/g rock). The middle part of the Lower Safa Member shows excellent organic richness (TOCm wt%: 5.39 and 22.90) of early postmature gas-prone carbonaceous material and coal deposits. These coaly shale layers exhibit fair to excellent wet gas and condensate generation potential (S2: 4.51–27.43, mg HC/g rock). Maturation of the source rocks was related to the Late Jurassic–Early Cretaceous Tethyan rifting. The onset of oil generation occurred in the Early Cretaceous (~ 116 Ma ago), while the onset of gas generation occurred in the Oligocene (~ 24 Ma ago). Shales of the Lower Cretaceous Alam El Bueib Fm are primary sealing rocks, while carbonates and shales of the Khatatba Fm are secondary sealing rocks. Trap types are structural, formed during the Late Jurassic and Early Cretaceous rifting of the Matruh Basin. Sandstones of the Upper Safa Member show upward increases in kaolinite and exhibit low-quality tight sandstone reservoirs. The Lower Safa Member sandstones show better gas reservoir quality with lower shale volumes. Operationally, the Lower Safa sandstone reservoirs in the Imhotep W-1X well are not suitable for gas production because they are ductile and show a high decline in production and pressure. Overall, the petroleum system of the Khatatba Fm shows mainly fair hydrocarbon potential in the study area.

Hematopoietic stem cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation have been critical in our fundamental understanding of HSC biology and developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone marrow (BM) niches. Various signaling molecules and growth factors secreted by HSCs and the niche microenvironment play critical roles in homing and engraftment of the transplanted cells. The sustained equilibrium of these chemical and biologic factors ensures that engrafted HSCs generate healthy and durable hematopoiesis. Transplanted healthy HSCs compete with residual host cells to repopulate stem cell niches in the marrow. Stem cell niches, in particular, can be altered by the effects of previous treatments, aging, and paracrine effects of leukemic cells that create inhospitable bone marrow niches that are unfavorable for healthy hematopoiesis. More work to understand how stem cell niches can be restored to favour normal hematopoieis may be key to reducing leukemic relapses following transplant.

Sepsis is an inflammatory disorder caused by the host’s dysfunctional response to infection. Septic patients present diverse clinical characteristics, and in the recent years it has been the main cause of death in intensive care units (ICU). Aquaporins, membrane proteins with role in water transportation, have been reported to participate in numerous biological processes. Their role in sepsis progression has been studied extensively. This review aims to examine recent literature on aquaporin expression and regulation in clinical sepsis, as well as established experimental models of sepsis. We will present how sepsis affects aquaporin expression at the molecular and protein level. Moreover, we will delve into the importance of aquaporin regulation at the transcriptional, post-transcriptional, translational, and post-translational level in sepsis, by presenting data on aquaporin regulation by non-coding RNAs and selected chemical molecules. Finally, we will focus on the importance of aquaporin single nucleotide polymorphisms in the setting of sepsis.

Background The coronavirus pandemic has led to the creation of clinical guidelines by a large number of professional medical communities. However, the quality and methodology of development of Russian clinical guidelines has been little studied. The continued relevance of studying the use of DOACs in patients with COVID-19 was the basis for conducting this study. Aim The objective of this study was to assess DOACs consumption and expenditures in Russian Federation during COVID-19 pandemic and to analyse domestic evidence base for the use of DOACs in COVID-19 patients through identifying all publicly available Russian-produced CPGs for the treatment of COVID-19 and assessing their quality as the source of recommendations for the use of oral anticoagulants for the prevention of thrombotic complications in COVID-19 patients. Methods We searched Russian databases for CPGs, published between 2020 and 2023. We identified 7 relevant documents that met our inclusion criteria. Three authors analyzed Russian clinical guidelines using a AGREE II questionnaire. We calculated DOACs DDD consumption according to Russian clinical guidelines and DDD consumption in patients with COVID-19 for the period 2020-2022. Results 7 clinical CPGs were analyzed with the AGREE II tool, it was revealed that experts gave the highest scores for the sections scope and purpose (from 62.98% to 100%), clarity of presentation (from 96.30% to 100%). The lowest scores were given for the sections stakenholder involment (33.33% to 64.81%), rigour of development (from 0% to 49.31%), applicability (from 23.61% to 50%), editory independence ( from 0% to 50%). When comparing the total score, it was found that two clinical guidelines received the highest scores - ROPNIZ (Livzan), ROPNIZ (Drapkina). The minimum score is registered with the NIIOZMM (Khripun) clinical guideline. No guideline received a total score of more than 70%. According to clinical recommendations, the consumption of apixaban and rivaroxaban is 15 DDD (30-day course of therapy), 22.5 DDD (45-day course of therapy). Consumption of apixaban in the Russian Federation in 2020 and 2021 corresponds to the indicators presented in clinical recommendations (in 2020 – 26.59 DDD per patient with COVID-19; in 2021 – 15.75 DDD per patient with COVID-19), and in 2022 – 10.67 DDD, which is below the recommended values. In 2020, consumption of rivaroxaban in the Russian Federation was 26.59 which corresponds to data from clinical recommendations; in 2021, consumption decreased to 7.87 DDD; in 2022 – 5.48 DDD, which is 2.74 times less than recommended.

Multidrug resistance (MDR) among gram-negative bacteria is a global public health threat because it has exhausted all standard therapeutic options. This has necessitated clinicians to reconsider colistin, an “old sort” antibiotic which was deemed toxic for clinical use. Unfortunately, swift resistance towards colistin by K. pneumoniae has been reported in different parts of the world. The study aimed at investigating the genetic determinants of colistin resistance in K. pneumoniae isolated from patients admitted in a tertiary care hospital in Kampala, Uganda. 31 archived multidrug resistant K. pneumoniae isolates obtained from rectal swabs of patients admitted to the Mulago Hospital ICU were retrieved. From this collection, we selected 7 colistin resistant K. pneumoniae isolates for whole genome sequencing and molecular profile analysis. In silico sequence data analyses were performed using established web-based bioinformatics tools. The sequence analysis of the genes involved in colistin resistance revealed several non-synonymous mutations in nucleotide sequences of pmrA, pmrB, phoP, phoQ and mgrB genes. Insertion transposase genes for the insertion sequences IS1 and IS5 which are highly implicated in colistin resistance via modification or inactivation of mgrB gene were identified in all isolates and were located in the chromosomal DNA at different genomic positions. No plasmid-borne mcr genes were detected. More so, the strains harbored numerous multidrug resistant genes. This study underscores the need of genomic surveillance of K. pneumoniae strains to limit further spread of colistin resistance genes to avert the potential risk of pandrug resistance. And high throughput sequencing is imperative.

Zero-dose children, or children who have not received any routine vaccination, are a priority population for global health policy makers as these children are at high risk of mortality from vaccine-preventable illnesses. We conducted a narrative review to identify potential interventions, both within and outside of the health sector, to reach zero-dose children. We reviewed peer-reviewed and grey literature and identified 59 relevant resources. Additionally, we interviewed six key informants to enhance synthesis of our findings. Data were organized into three priority settings: (1) urban slums, (2) remote or rural communities, and (3) conflict settings. We found that zero-dose children in the three-priority settings face differing barriers to vaccina-tion and, therefore, require context-specific interventions, such as leveraging slum health commit-tees for urban slums or integrating with existing humanitarian response services for conflict set-tings. Three predominant themes emerged for grouping the various interventions: (1) community engagement, (2) health systems strengthening and integration, and (3) technological innovations. The barriers to reaching zero-dose children are multifaceted and nuanced to each setting, there-fore, no one intervention is enough. Technological interventions especially must be coupled with community engagement and health systems strengthening efforts. Evaluations of the suggested interventions are needed to guide scale up, as the evidence-base around these interventions is rel-atively small.

This study scrutinizes the complexities of designing and exploring the potential energy surface (PES) of systems containing more than twenty atoms with planar tetracoordinate carbons (ptCs). To tackle this issue, we utilized an established design rule to design a Naphtho [1,2-b:4,3-b′:5,6-b′′:8,7-b′′′]tetrathiophene derivative computationally. This process began with substituting S atoms with CH– units, then replacing three sequential protons with two Si2+ units in the resultant polycyclic aromatic hydrocarbon polyanion. Despite not representing the global minimum, the newly designed Si8C22 system with four ptCs provided valuable insights into strategic design and PES exploration. Our results underscore the importance of employing adequate methodologies to confirm the stability of newly designed molecular structures containing planar hypercoordinate carbons.

A land cover map of two arctic catchments, nearby the Abisko Scientific Research Station, was obtained from a classification of a Sentinel-2 satellite image and a ground survey performed in July 2022. The two contiguous catchments, Miellajokka and Stordalen, are covered by various ecotypes, from boreal forest to alpine tundra and peatland. The Random Forest algorithm correctly identified 83% of polygon pixels reserved for testing. The developed workflow relied solely on open source software and acquired ground observations. Space organization was directed by the altitude as shown by the intersection of the land cover with the topography. Comparison between this new land cover map and previous ones based on data acquired between 2008 and 2011 demonstrates some trends of vegetation cover evolution in response to climate change in the considered area. The potential applications in terms of permafrost modeling (hiperborea.omp.eu) are finally discussed.

Precise association of serum leptin with body mass index (BMI) and blood pressure (BP; both systolic blood pressure (SBP) and diastolic blood pressure (DBP) is not well known for understanding their involvement in health and disease. Hence, the present study was planned to be conducted for investigating the association of BP, BMI and serum leptin levels in young normal weight (NW) and overweight (OW) male Saudi students. The NW (n: 198) and OW male subjects (n: 192) in the age range of 18-20 years were consulted. Blood pressure (BP) was measured with a mercury sphygmomanometer. Leptin Human ELISA Kits were employed for the determination of the serum leptin levels. The mean ± SD values of BMI (kg/m2), serum leptin (ng/ml), SBP (mmHg), and DBP (mmHg) all showed significant difference for young OW vs. NW male university students as: 27.52± 1.42 vs. 21.49± 2.03; 10.70± 4.67 vs. 4.68± 1.91; 121.37±2.59 vs.118.51±1.54 and 81.44±1.97 vs. 78.79±1.44 respectively. All associations (among BMI, leptin, SBP and DBP) showed positive linear and significant correlation except nonsignificant correlation of BMI and SBP for NW group. The present study in the young Saudi male students, presents significant variations for BP and serum leptin levels and significant positive linear association among serum leptin, BMI and BP.

The rhizosphere is a rich source of actinomycetes which can produce several potential biologically-active secondary metabolites. The principal goals for this research are to extract, purify and characterize the bioactive secondary metabolites produced by three different strains of actinomycetes isolated from the rhizosphere of rosemary, black locust and olive. The plant growth-promoting effect (PGPE) of the studied strains of actinomycetes on Ocimum basilicum L. (basil) and disease-control effect on necrotic stem lesions of “black leg” caused by Fusarium tabacinum on basil, were in silico evaluated. The cell-free culture filtrates from the studied actinomycetes isolates were evaluated in vitro for their antimicrobial activity against some common phytopathogens. The secondary metabolites obtained from the cell-free culture filtrates have been chemically characterized using high‐resolution electrospray ionization of liquid-chromatography/mass-spectrometric detection (ESI-(HR)Orbitrap-MS). Results of in silico trial showed that all studied isolates demonstrated PGPE on basil seedlings improving some Eco-physiological characteristics and reduced the disease incidence of F. tabacinum. The extracted metabolites from the studied actinomycetes demonstrated antimicrobial activity in Petri-plates assay. The chemical analysis revealed the presence of totally 20 different components. This research emphasizes how valuable the examined isolates are for producing bioactive compounds, indicating their putative antimicrobial activity and their potential employment as fungal-biocontrol agents. In particular, the obtained results revealed the possibility of green-synthesis of some important secondary metabolites such as N-Acetyl-L-histidinol, Rhizocticin A and Eponemycin from actinomycetes. The bioactive metabolites may be successively used to develop novel bio-formulations for both crop protection and/or PGPE.

Abstract: Cancer cells are originated by normal cells and with those share the need to be fed. Metabolic reprogramming in cancer cells is not yet fully understood although there is a vast literature suggesting that huge amounts of both energy and substrates are require for synthesis of components of new neoplastic cells so that any macronutrient may be efficiently utilized. Recently, in vitro data show that EAA supplementation promoted colon cancer cells apoptosis by enhanced autophagy. Therefore, in this study we tested in vivo the effects of matched macronutrients standard laboratory diet (control) versus EAA rich modified diet (EAArmd) in mice injected with colon cancer cells. Results of the first set of 12 animals, 6 controls and 6 EAArmd-fed, showed that controls mice develop cancer volume cancers 5 times larger and heavier than EAArmd-fed. If confirmed, these results would open new scenarios for the cancer integrate therapies.

Rapid solidification during metal additive manufacturing (AM) leads to non-equilibrium microsegregation, which can result in the formation of detrimental phases and cracking. Most of the microsegregation models, assume a Scheil-type solidification, where the solidification interface is planar and there exists local equilibrium at the interface along with either zero or infinite solute diffusion in the respective participating phases - solid and liquid. This assumption leads to errors in prediction. One has to account for finite solute diffusion and the curvature at the dendritic tip for more accurate predictions. In this work, we compare different microsegregation models that do and do not consider finite diffusion and dendrite tip kinetics against the experiments. We also propose a method to couple dendrite tip kinetics with the diffusion module (DICTRA®) implemented in Thermo-Calc®. The models which accounted for both finite diffusion and dendrite tip kinetics matched well with the experimental data.

: Cancer metastasis is the lethal developmental step in cancer, responsible for the majority of cancer deaths. To metastasize, cancer cells must acquire the ability to disseminate systemically and to escape an activated immune response. Here, we endeavoured to investigate if metastatic dissemination reflects acquisition of genomic traits that are selected for. We acquired mutation and copy number data from 8,332 tumours representing 19 cancer types acquired from The Cancer Genome Atlas and the Hartwig Medical Foundation. A total of 827,344 non-synonymous mutations across 8,332 tumour samples representing 19 cancer types were timed as early or late relative to copy number alterations, and potential driver events were annotated. We found that metastatic cancers had significantly higher proportion of clonal mutations and a general enrichment of early mutations in p53 and RTK/KRAS pathways. However, while individual pathways demonstrated a clear time-separated preference for specific events, the relative timing did not vary between primary and metastatic cancers. These results indicate that the selective pressure that drives cancer development does not change dramatically between primary and metastatic cancer on a genomic level, and is mainly focused on alterations that increase proliferation.

Gas-liquid mass transfer is a significant issue in most bioprocesses. More importantly, gas-liquid mass transfer limitation requires further attention during syngas fermentation (SNF). The gas-liquid mass transfer of gaseous substrates (CO, CO2, and H2) into the fermentation broth is a rate-limiting step in SNF that leads to low productivity and poor economic feasibility. Enhancing this process during SNF can result in high efficiency, better production of ethanol, as well as lower energy consumption. While pressure and power input are important factors for improving reactor design, adding magnetic nanoparticles (MNPs) in the liquid phase is critical to achieving an enhanced gas-liquid mass transfer. The present study reviewed recent advances in the application of MNPs for an improved gas-liquid mass transfer during syngas fermentation. A brief overview of SNF and the effects of MNPs on SNF process are outlined. In addition, the hydrodynamic effect at the gas-liquid boundary is also seen as a mechanism in which nanoparticles increase mass transfer, and the mechanism is elucidated in detail.

In Europe, the recent application of regulations oriented to zero-energy buildings and climate neutrality in 2050 has led to a reduction in energy consumption for heating and cooling in the construction sector. The thermal insulation of the building envelope plays a key role in this process and the requirements about the maximum allowable thermal transmittance are defined by country-specific guidelines. Typically, high insulation values provide low energy consumption for heating, however, they may paradoxically imply the risk of overheating in summer period and thus negatively affect the overall performance of the building. In addition, the embodied energy and related emissions caused by the manufacturing and transportation processes of thermal insulation cannot be further neglected in the evaluation of the best optimal solution. Therefore, this paper aims to evaluate the influence in terms of embodied and operational energy of various walls’ thermal insulation thicknesses on residential buildings in Europe. To this end, the EnergyPlus engine was used for the energy simulation within Ladybug &amp; Honeybee tools, by parametrically conducting multiple iterations; 53 variations of external wall U-value, considering high and low thermal mass scenarios, were simulated for 100 reference cities of the European context, using a representative multifamily building as a reference. The results demonstrate that massive walls generally perform better than lightweight structures and, of course, the best solution in terms of energy varies according to each climate. The optimal values are graphically reported on the map of Europe according to specific climatic features, providing a guidance for new constructions and building retrofit.

Biofouling is the unwanted adsorption of cells, proteins, or intracellular and extracellular bio-molecules that can spontaneously occur on the surface of metal nanocomplexes. It represents a major issue in bioinorganic chemistry because it leads to the creation of a protein corona, which can destabilize a colloidal solution and result in undesired macrophage-driven clearance, consequently causing failed delivery of a targeted drug-cargo. Hyaluronic acid (HA) is a bioactive, natural mucopolysaccharide with excellent antifouling properties, arising from its hydrophilic and polyanionic characteristics in physiological environments which prevent opsonization. In this study, hyaluronate-thiol (HA-SH) (MW 10 kDa) was used to surface-passivate gold nanoparticles (GNPs) synthesized using a citrate reduction method. HA functionalized GNP complexes (HA-GNPs) were characterized using absorption spectroscopy, scanning electron microscopy, zeta potential, and dynamic light scattering. GNP cellular uptake and potential dose-dependent cytotoxic effects due to treatment were evaluated in vitro in HeLa cells using ICP-OES and Trypan blue and MTT assays. Further, we quantified the in vivo biodistribution of intratumorally injected HA functionalized GNPs in Lewis Lung carcinoma (LLC) solid tumors grown on the flank of C57BL/6 mice and compared localization and retention with nascent particles. Our results reveal that HA-GNPs show overall greater peritumoral distribution (**p<0.005, 3 days post-intratumoral injection) than citrate-GNPs with reduced biodistribution in off-target organs. This property represents an advantageous step forward in localized delivery of metal nano-complexes to the infiltrative region of a tumor, which may improve the application of nanomedicine in the diagnosis and treatment of cancer.

This study investigated the influence of land-use and precipitation change and variability on Lake Victoria’s water-level fluctuations. Extreme precipitation events, corresponding to extreme water-levels, over the lake and its catchment area were identified and their return periods estimated by fitting them into a generalized extreme value (GEV) distribution. Using general circulation models from the 6^th phase of the Coupled Model Intercomparison Project (CMIP6)’s Detection & Attribution Model Intercomparison Project (DAMIP), an assessment of the potential contribution of human-induced climate change on the observed precipitation patterns over the study area was done. The greatest precipitation anomalies for the period 1900-2020 were recorded in 1961’s October-December (OND) season and 2019’s June-August (JJA) and OND seasons, corresponding to the period when the highest water-levels were recorded in Lake Victoria. While land-use change in the study domain was observed, extended and unusually heavy June to December 2019 precipitation bore the greatest responsibility for the 2019/2020 high water-levels in Lake Victoria. The OND precipitation event of 2019 was a 1-in-52-year event compared to the 1961’s 1-in-693 years. Differences in return periods at various parts of the lake imply a high spatial climate variability within the lake itself. An analysis of the fraction of attributable risk (FAR) showed natural variability to have a greater influence on the JJA and OND precipitation patterns over Lake Victoria than human-induced climate change. However, variability over the land area of the study domain was mainly driven by human-induced climate change rather than natural variability, implying a unique climate system over Lake Victoria. Findings from the current study enhance the understanding of Lake Victoria’s water budget and motivate for further research to inform effective strategies on the planning and use of Lake Victoria’s water resources in a changing climate.

Due to their well-defined plasmonic properties, gold nanorods (GNRs) can be fabricated with optimal light absorption in the near-infrared region of the electromagnetic spectrum, which make them suitable for cancer-related theranostic applications. However, their controversial safety profile, as a result of surfactant stabilization during synthesis, limits their clinical translation. We report a facile method to improve GNR biocompatibility through the presence of sodium dodecyl sulfate (SDS). GNRs (120 x 40 nm) were synthesized through a seed-mediated approach, using cetyltrimethylammonium bromide (CTAB) as a cationic surfactant to direct the growth of nanorods and stabilize the particles. Post-synthesis, SDS was used as an exchange ligand to modify the net surface charge of the particles from positive to negative while maintaining rod stability in an aqueous environment. GNR cytotoxic effects, as well as the mechanisms of their cellular uptake, were examined in two different cancer cell lines, Lewis lung carcinoma (LLC) and HeLa cells. We not only found a significant dose-dependent effect of GNR treatment on cell viability but also a time-dependent effect of GNR surfactant charge on cytotoxicity over the two cell lines. Our results promote a better understanding of how we can mediate the undesired consequences of GNR synthesis byproducts when exposed to a living organism, which so far has limited GNR use in cancer theranostics.

Savouring is an emotion regulation strategy and intervention that focuses on the process of attending, intensifying and prolonging positive experiences and positive affect associated with these memories. Personal savouring involves a reflection on positive memories that are specific to the individual and do not involve others. In contrast, relational savouring entails reflecting on instances when people were responsive to the needs of their significant others. Such interventions hold potential to benefit parents of children with autism spectrum disorder (ASD). Mothers of children with ASD tend to experience higher anxiety, lower positive affect (PA) and more negative affect (NA) compared to mothers of neurotypical children, leading to a diminished overall well-being. Moreover, ASD has multiplied by up to four times in the recent decade. Thus, this paper investigates whether savouring may enhance the overall well-being of mothers of young children with ASD by increasing positive affect and decreasing negative affect. 52 mothers of neurotypical children and 26 mothers of children with ASD aged 3-7 years old were given a series of questionnaires and randomly assigned to either relational savouring or personal savouring conditions. In relational savouring, mothers were asked to reflect upon a shared positive experience with their child while in the personal savouring condition, a personal positive experience was recalled. Across mothers of children with ASD and neurotypical children, findings suggest that savouring leads to a decrease in NA (p &lt; .01) but not increases in PA. Similarly, mothers with higher levels of anxiety experience a greater decrease in NA (p &lt; .001) compared to mothers with lower levels of anxiety post-savouring. This study proposes that a brief savouring intervention may be effective among mothers of preschoolers. As lower levels of negative affect is linked to healthier psychological well-being, mothers might be able to engage in more effective and warm parenting after savouring exercises, which would cultivate positive mother-child relationships that benefit their children in the long-term.

Metabolically unhealthy obesity (MUO) was associated with increased cardiometabolic risk. However, it is not fully understood which lifestyle factors are associated with MUO in youth. We aimed to investigate the relationship between MUO and lifestyle patterns in youth. 7-17 years old youth with overweight (N=48; 60.4% girls) and obesity (N=71; 56.3% girls) were recruited in the Pediatric Clinic, Luxembourg (cross-sectional study). Eating and sedentary habits, moderate to vigorous physical activity (MVPA) and vigorous physical activity (VPA) were assessed. 72.3% of the participants had MUO. Multivariable logistic regressions showed that MUO is most likely to be associated with moderate to low weekly levels of MVPA [OR: 2.09 (95% CI: 1.07 – 4.09; p = 0.030)] and moderate to high weekly soda and lemonade drinks consumption [OR: 2.92 (95% CI: 1.32 – 6.48; p = 0.008)]. After adjustment for age, gender and Tanner stages, MUO was most likely to be associated with moderate to high soda and lemonade drinks consumption [OR: 2.72 (95% CI: 1.21– 6.12; p = 0.016)] and with Tanner stages [OR: 2.06 (95% CI: 1.08– 3.94; p = 0.029)]. We support the promotion of MVPA and the moderation in the sugar-sweetened beverages consumption to manage cardiometabolic health in youth with obesity.

This paper presents a system that merges computer vision and surface electromyography techniques to carry out grasping tasks. To perform this, the vision-driven system is used to compute pre-grasping poses of the robotic system based on the analysis of tridimensional object features. Then, the human operator can correct the pre-grasping pose of the robot using surface electromyographic signals from the forearm during wrist flexion and extension. Weak wrist flexions and extensions allow a fine adjustment of the robotic system to grasp the object and finally, when the operator considers that the grasping position is optimal, a strong flexion is performed to initiate the grasping of the object. The system has been tested with several subjects to check its performance showing a grasping accuracy of around 95% of the attempted grasps which increases by around a 9% the grasping accuracy of previous experiments in which electromyographic control was not implemented.

Biomarkers have the potential to aid in the study of Alzheimer’s disease (AD); unfortunately, AD biomarker values often have a high degree of overlap between healthy and AD individuals. This study investigates the potential utility of a series of novel AD biomarkers, the sixty second ¹²⁹Xe retention time, and the xenon washout parameter, based on the washout of hyperpolarized ¹²⁹Xe from the brain of AD participants following inhalation. The xenon washout parameter is influenced by cerebral perfusion, T1 relaxation of xenon, and the xenon partition coefficient, all factors influenced by AD. Participants with Alzheimer’s disease (n=4) and healthy volunteers (n=4) were imaged using hyperpolarized ¹²⁹Xe magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to determine the amount of retain xenon in the brain. At 60 sec post breath hold, AD patients retained significantly higher amounts of ¹²⁹Xe compared to healthy controls. Data was fit to a pharmacokinetic model and the xenon washout parameter was extracted. Xenon washout in white and grey matter occurs at a slower rate in Alzheimer’s participants (¹²⁹Xe half-life time of 42s and 43s, respectively) relative to controls (20s and 16s, respectively). Following larger scale clinical trials for validation, the xenon washout parameter has the potential to become a useful biomarker for the support of an AD diagnosis.

Embryonic and larval Danio rerio is increasingly used as a toxicological model to conduct rapid in vivo tests and developmental toxicity assays; the zebrafish features as high genetic homology to mammals; robust phenotypes; and its value in high-throughput genetic and chemical screening have made it a powerful tool to evaluate in vivo toxicity. New methodologies of genome editing as CRISPR/Cas9; ZFN or Talen make it a suitable model to perform studies to pair human genetic diseases as well. This review surveys recent studies; employing zebrafish as experimental model; comparing it with other in vivo and in vitro models; presenting zebrafish as a potent vertebrate tool to evaluate drug toxicity to facilitate more extensive; easy and comprehensive knowledge of new generation drugs.

A compact Mach-zehnder interferometer with a novel design of directional couplers and a phase shifter has been presented as a thermo-optical sensor. With the aim of reducing device size to micro and nano dimension silicon-on-insulator technology was employed. That allowed miniaturization of device size through the reduction of its cross sectional area to 0.066 µm² and the radius of curvature of both the arms of the directional coupler and S-bends of the phase shifter to 5 µm and C-bends to 3 µm. These nano size device dimensions made it possible to reduce the coupling gap to 0.2 µm, which resulted in a significant reduction in the coupling length. The device geometry and its performance characteristics were analyzed and optimized using coupled mode analysis and finite difference time domain simulation tools, respectively. The wavelength dependent transmission loss of the device was measured at different temperature to verify and validate its performance characteristics. Tested devices showed a remarkable temperature dependent transmission characteristic offering significant changes in transmission loss band – with as low as 0.45 ⁰C change in substrate temperature. The extinction ratio and the free spectral range of the device were 26 dB and 0.26 nm respectively in the wavelength range of 1549.5 nm – 1550.5 nm. These results imply that the devices presented here can be used as compact and highly sensitive thermal sensors and optical switches.

To assess the efficacy of washing cloth masks, we simulated SARS-CoV-2 contamination in tricoline fabric and tested decontaminants to reduce viral particles. Viral suspensions using two variants (B.1.1.28 and P.1) were inoculated in these fabrics, and the inactivation kinetics were evaluated after washing with various household disinfection products (Soap powder, Lysoform®, Hypochlorite sodium and 70% Alcohol), rinse numbers, and exposure times. Afterward, the fabrics were washed in sterile water, viral RNA extracted and amplified using RT-qPCR. Finally, viral replication in cell cultures was examined. Our findings show that all biocidal treatments successfully disinfected the tissue tested. Some products showed less reduction in viral loads, Soap powder (1.60 x 104, 1.04 x 103), Soap powder and Lysoform® (1.60 x 104, 1.04 x 103) and Alcohol 70% (1.02 x 103, 5.91 x 101) respectively. However, when sodium hypochlorite was used, this reduction was significantly increased (viral inactivation in 100% of the washes). After the first wash, the reduction of viral particles was greater for the P.1 variant than for the B.1.1.28 variant (W = 51759, p 0.05). In conclusion the sodium hypochlorite role on cloth masks disinfection may also have implications for future health emergencies as well as recommended by WHO.

Review of the existing bibliography shows that the direction and magnitude of the long-term trends of UV irradiance, and their main drivers, vary significantly throughout Europe. Analysis of total ozone and spectral UV data recorded at four European stations during 1996 – 2017 reveals that long-term changes in UV are mainly driven by changes in aerosols, cloudiness, and surface albedo, while changes in total ozone play a less significant role. The variability of UV irradiance is large throughout Italy due to the complex topography and large latitudinal extension of the country. Analysis of the spectral UV records of the urban site of Rome, and the alpine site of Aosta reveals that differences between the two sites follow the annual cycle of the differences in cloudiness and surface albedo. Comparisons between the noon UV index measured at the ground at the same stations and the corresponding estimates from the DWD forecast model and OMI/Aura observations reveal differences of up to 6 units between individual measurements, which are likely due to the different spatial resolution of the different datasets, and average differences of 0.5 – 1 unit, possibly related to the use of climatological surface albedo and aerosol optical properties in the retrieval algorithms.

Enamel matrix derivative (EMD) is used for periodontal tissue regeneration therapy, and can induce mineralization in dental pulp cells (DPCs). We designed a synthetic peptide (SP) derived from the response of cells to EMD, and investigated the effect of the SP on potentiating osteogenesis in DPCs, which have a critical role of dental pulp homeostasis. DPCs were treated with 0, 10, 100, or 1000 ng/mL SP to determine its effect on cell proliferation, cell migration, cell differentiation, and mineralization. We then examined the molecular effects of the SP, focusing on changes in the mitogen-activated protein kinases (MAPK) signaling pathway in these cells. The SP significantly promoted DPC proliferation and migration. Cultures treated with the SP also showed an enhanced expression of markers of osteogenic differentiation and mineralization. The SP also induced the activation of MAPK signaling pathway components. These results suggest that our SP could promote the dental pulp tissue repair by hard tissue formation and the mineralization through activating MAPK signaling pathway. This study provides the first evidence that SP might be a new material for dental pulp tissue treatment.

Research in complex network analysis, including tasks such as information dissemination and link prediction, has traditionally advanced by examining groups of nodes with similar characteristics. In multilayer complex networks, these analyses are performed layer-wise, with each layer representing a distinct feature. However, this approach often neglects interlayer interactions, leading to limited predictive power, underestimation of network resilience, and incomplete identification of influential nodes. This article introduces a novel block modeling technique that integrates dominant features from multiple layers, addressing these shortcomings. Our approach introduces a new centrality metric that combines layer weight and PageRank centrality to identify influential nodes within multilayer networks. Nodes are aggregated into blocks centered around these influencers, accounting for both intra- and interlayer connections. Empirical evaluation of various datasets demonstrates that our method effectively identifies influential nodes, thereby enhancing information dissemination and link prediction across diverse multilayer network structures. This technique offers significant potential for improving decision-making processes in various fields, including social network analysis, transportation systems, and biological networks.

The International Renewable Energy Agency (IRENA) was established in 2009 and in 2024, its membership increased to 168 members plus the European Union countries. The purpose of IRENA is to promote the adoption of renewable energy across all industries in the world. Despite the utilization of renewable energy in sectors like power generation and construction, its application in other industries remains limited. Therefore, a literature review study was conducted to investigate the cost and other spatial constraints associated with renewable energy resources, including modeling and optimization techniques that could offer viable solutions to the future challenges faced by the renewable energy production systems. This paper has summarized the result of this study with a focus on the significance of modeling and optimization techniques in energy conservation to highlight the untapped potential for leveraging renewable energy resources in industrial applications. This paper also examined a few case studies from various regions of the world, demonstrating the promising opportunities for research in the modeling and optimization of renewable energy management systems.

Objective: The key to the success of pedicled skin flaps in the head and neck region is preserved perfusion. The use of thermal imaging can provide an indirect indicator of tissue perfusion, which consecutively would be of interest for perioperative prediction of the viability. The effectiveness of thermal imaging has already been demonstrated for assessing pedicled and free flaps [1]. This work investigates the implementation of SBTI as a noninvasive and cost-efficient method in clinical practice for predicting the vitality and perioperative monitoring of pedicled skin flaps in head and neck surgery. Methods: The FLIR One Pro camera was used for this pilot study (Teledyne FLIR LLC, Wilsonville, Oregon, United States). It is a multispectral camera that contains a near-infrared camera unit with a resolution of 160 x 120 pixels, a temperature range of 0 ° - 400 °C, and a thermal resolution of 70 millikelvin. For the study, after implementing the system, n = 11 skin flaps were photographed by SBTI (n=44) after marking (T1), after elevation (T2), after completed surgery (T3), and 24 hours postoperatively (T4), and the outcome was assessed clinically in correlation after one week by one surgeon. Results: The pedicled skin flaps examined all showed a preserved, uniform thermal image signature peri- and postoperatively for time points T1-4. This corresponded to a good postoperative result regarding the vitality of the tissue transfer in the clinical assessments 24 hours and one week postoperatively. Conclusion: The acquisition of a continuously obtained thermal image signature as a surrogate marker for preserved tissue perfusion by SBTI proved simple, inexpensive, noninvasive, and efficient in the present sentinel study. The application of SBTI has been primarily investigated in identifying perforators in large pedicled or free flaps. [2, 3] The concordance of the obtained thermal image signature with a positive clinical outcome suggests that the presented method is also suitable for perioperative prognostic statements on postoperative flap vitality in pedicled skin flaps and for monitoring those during surgery. Further studies are necessary for the implementation of this method in clinical practice to support the surgeon's intraoperative decision-making in the future.

Following the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) joint guide-lines (2018) for the management of patients with cervical cancer, treatment decisions should be guided by modern imaging techniques. After five years (2023), an update of the ES-GO-ESTRO-ESP recommendations was performed furtherly confirming this statement. Trans-vaginal/transrectal ultrasound (TRS/TVS) or pelvic magnetic resonance (MRI) enables tumour delineation and precise assessment of its local extent, including the evaluation of the depth of infiltration in the bladder- or rectal wall. Additionally, both techniques have very high specificity to confirm the presence of metastatic pelvic lymph nodes but fail to exclude them due to insuffi-cient sensitivity to detect small-volume metastases, as any other currently available imaging modality. In early-stage disease (T1a to T2a1, except T1b3) with negative lymph nodes on TVS/TRS or MRI, surgicopathological staging should be performed. In all other situations, con-trast-enhanced computed tomography (CECT) or 18F-fluorodeoxyglucose positron emission tomography in combination with CT (PET-CT) are recommended to assess extrapelvic spread. The aim of this paper is to review the evidence supporting the implementation of diagnostic imaging with a focus on ultrasound at primary diagnostic workup of cervical cancer.

[Objective] To investigate the expression of ALDH2 in hepatocellular carcinoma and its correlation with macrophage infiltration and with the activation of specific subtypes of macrophages. [Methods] Transcriptome and clinical data from patients with hepatocellular carcinoma were downloaded from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases and analyzed and collated using R and Perl software. In the TCGA hepatocellular carcinoma dataset, the Wilcoxon test was used to identify macrophage activation-related gene sets that show differential expression between hepatocellular carcinoma and normal tissues. Single-cell sequencing combined with bulk data was used to analyze macrophage infiltration of hepatocellular carcinoma immune cells and the activation and recruitment of different subtypes of macrophages. Single-factor Cox regression and minimum absolute convergence and selection operator (Lasso) were used to identify survival-related genes and construct prognostic models of HCC. The patients were divided into two groups based on their model scores. The Wilcoxon test was used to identify differentially expressed genes (DEGs) between the two groups, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of the DEGs were performed. Single-sample gene set enrichment analysis (ssGSEA) was performed to explore the possible mechanism underlying the differences in prognosis. The reliability of the model was verified using the ICGC hepatocellular carcinoma dataset. A Kaplan‒Meier curve was constructed and used to analyze the influence of macrophage activation-related gene expression on survival and prognosis in patients with hepatocellular carcinoma. The log-rank test and the independent t test were used to analyze survival time data and to compare immune cell infiltration in the two groups. [Results] In a comparison of hepatocellular carcinoma and paracancerous tissues, the expression of six of 137 macrophage activation-related genes (ALDH2, CCNB2, CYP2C9, CYP3A4, F9 and KLKB1) was found to be significantly correlated with overall survival time (OS) in patients with hepatocellular carcinoma. Based on this finding, a prognosis assessment model for hepatocellular carcinoma was constructed. The OS of the patients in the high-scoring group was significantly shorter than the OS of the patients in the low-scoring group (P<0.05), and the model predicted the prognosis of patients with hepatocellular carcinoma independently of sex, age, tumor grade and stage. The area under the receiver operating characteristic (ROC) curve of the model used to predict 1-, 2-, and 3-year survival was greater than 0.7 in both the test set and the validation set. GO enrichment of DEGs between the high- and low-scoring groups of the model suggested that the DEGs are mainly related to immune function. GSEA suggested that the tumor-infiltrating immune cells in the high-scoring group were macrophages, Th2 cells and Treg cells and showed that the number of tumor-infiltrating immune cells, including NK cells, was lower in the high-scoring group than in the low-scoring group. With respect to immune function, the immune checkpoint of the high-scoring group was higher than that of the low-scoring group. Single-cell sequencing data indicated the recruitment of B cells, M0 cells, M1 cells and M2 cells to the hepatocellular carcinoma microenvironment and suggested that ALDH2 regulates related signaling pathways in a way that promotes the differentiation of macrophages into M2-type macrophages. [Conclusion] M2-type macrophages are the dominant type of macrophages associated with immune infiltration in hepatocellular carcinoma. The macrophage-associated activation gene ALDH2 activates the macrophage polarization signaling pathway and negatively regulates the differentiation of macrophages into M2-type macrophages.

The concept and policies of multiple early cancer detection (MCED) have gained significant attention from governments worldwide in recent years. In the era of burgeoning artificial intelligence (AI) technology, the integration of MCED with AI has become a prevailing trend, giving rise to a plethora of MCED AI products. However, due to the heterogeneity of both the detection targets and the AI technologies, the overall diversity of MCED AI products remains considerable. The types of detection targets encompass protein biomarkers, cell-free DNA, or combinations of these biomarkers. In the development of AI models, different model training approaches are employed, including datasets of case-control researches or real-world cancer screening datasets. Various validation techniques, such as cross-validation, location-wise validation, and time-wise validation are used. All of the factors show significant impacts on the predictive efficacy of MCED AIs. After the completion of AI model development, deploying the MCED AIs in clinical practice presents numerous challenges, including presenting the predictive reports, identifying the potential locations and types of tumor, and addressing cancer-related information such as clinical follow-up and treatment. This study reviews several mature MCED AI products currently available in the market, detecting their composing factors from serum biomarkers detection, MCED AIs training/validation, and the clinical application. The review illuminates the challenges encountered by existing MCED AI products across these stages, offering insights into the continued development and obstacles within the field of MCED AI.

The widespread use of hydrophilic intraocular lenses (IOL) in eye surgery, fabricated by poly-2- (hydroxyethylmethacrylic acid) (PHEMA), has highlighted their calcification as a serious problem, which implies their surgical explantation a rather risky process. The field of biomaterials has been developing rapidly in recent years with research interest turning to the development of novel ma-terials which involve either copolymers of PHEMA or protective functional coatings. Graphene coatings are particularly attractive because of the respective unique properties. In the present work we present the results of the investigation of the development of graphene coatings on hydrophilic IOLs and their subsequent performance with respect to calcification opacification. Hydrophilic IOL with water content of 18% by weight, were coated with graphene oxide (GO) by equilibration with GO suspensions in water. The concentrations of the suspensions ranged 1x10-4 to 20x10-4 % w/v. The GO suspensions were equilibrated with the IOLs for 5 days at constant temperature, 37°C, rotated in 30 mL tubes end over end. This treatment, resulted in the formation of a uniform coating of GO on the IOLs verified by scanning electron microscopy (SEM) and other physicochemical methods. The contact angle of the GO coated IOLs decreased significantly in comparison with the uncoated. The GO-coated IOLs exhibited higher tendency to calcify in supersaturated solutions simulating aqueous humor (SAH). The growth rate of hydroxyapatite (Ca5(PO4)3OH, HAP) on GO-coated IOLs was higher, in comparison with the respective untreated IOLs. The conversion of the GO coating by reduction with phenyl hydrazine resulted in the formation of reduced graphene (rGO) surface film, identified by Raman and XPS spectroscopy. of the rGO film was hydrophobic (contact angle 100 o) and did not calcify in supersaturated calcium phosphate solutions.

Formaldehyde, sulfuric acid and salicylic acid were combined to create 3,3’-methylenebis[2-hydroxybenzoic acid] (MHB) ligand, which was subsequently permitted to bind with zinc ions. The ligand and its zinc (II) complex (Zn-MHB) have been described by a combination of elemental analyses, spectral (UV-Vis, IR, MS, NMR), XRD, TEM as well as TGA measurement. The ligand has been suggested to coordinate to the zinc center in tetradentate manner forming binuclear tetrahedral complex. An X-ray analysis indicated a considerable difference between MHB (crystalline) and Zn-MHB (amorphous). UV-Vis spectra were used to determine the optical properties such as bandgap, refractive index, optical conductivity and penetration depth. Possibility of employing the samples for optoelectronic applications was indicated from the band gap values which underlie the range of semiconductors. TEM revealed spherical shapes and mutation of ligand particles into nano-scale by complexation. The antimicrobial potential of the MHB towards gram-positive and negative bacterial growths has been investigated. The results suggested that it would be possible to employ MHB to stop bacterial development, particularly salmonella typhimurium. Cytotoxicity of the MHB was assessed against two types of mammalian cells: VERO (the kidney of an African green monkey) and HFB4 (human skin melanocytes). Lower sensitivity was observed in VERO cells.

Transposable elements (TEs) are repetitive elements which make up around 45% of the human genome. A class of TEs known as SINE-VNTR-Alu (SVA) demonstrate the capacity to mobilise throughout the genome, resulting in SVA polymorphisms for presence or absence within the population. Although studies have previously highlighted the involvement of TEs within neurodegenerative diseases, such as Parkinson’s disease and amyotrophic lateral sclerosis (ALS), however the exact mechanism has yet to be identified. In this study we used whole genome sequencing and RNA sequencing data of ALS patients and healthy controls from the New York Genome Center ALS Consortium, to elucidate the influence of reference SVA elements on gene expression genome-wide within central nervous system (CNS) tissues. To investigate this, we applied matrix expression quantitative trait loci analysis and demonstrated that reference SVA insertion polymorphisms can significantly modulate the expression of numerous genes, preferentially in the trans position, and in a tissue-specific manner. We also highlight that SVAs significantly regulate mitochondrial genes as well as genes within the HLA and MAPT loci, previously associated within neurodegenerative disease. In conclusion, this study continues to bring to light the effects of polymorphic SVAs on gene regulation and further highlights the importance of TEs within disease pathology.

The development of modern genomic tools has sped up the breeding program of food crops. More recently, genomic resources are being developed for tropical forages and will be key resources for developing climate resilient high yielding forage varieties. In this study, we present a genome-wide association study for biomass yield and feed quality traits in buffel grass (Cenchrus ciliaris L. aka Pennisetum ciliare L.,). Genome-wide markers generated using the DArTSeq platform and mapped onto the reference genome of Setaria italica were used for the genome-wide association study. The results revealed several markers associated with biomass yield and feed quality traits. A total of 78 marker trait associations were identified with R2 values ranging from 0.138 to 0.236. The marker trait associations were distributed across different chromosomes. Of these associations, the most marker trait associations (23) were observed on Chr9, followed by Chr5 with 12. The fewest number of marker trait associations were observed on Chr4 with 2. In terms of traits, 17 markers were associated with biomass yield, 24 with crude protein, 26 with TDN, 14 with ADF, 10 with NDF and six with DMI. Twenty of the identified markers were associated with at least two traits. The identified marker trait associations provide a useful genomic resource for future improvement and breeding of buffel grass.

Thoracic aortic aneurysm (TAA) has a prevalence of 0.16%-0.34% and an incidence of 7.6 per 100,000 person-years, accounting for 1%-2% of all deaths in Western countries. Currently, no effective pharmacological therapies have been identified to slow TAA development and prevent TAA rupture. Large TAAs are treated with open surgical repair and less invasive thoracic endovascular aortic repair, both of which have high perioperative mortality risk. Therefore, there is an urgent medical need to identify the cellular and molecular mechanisms underlying TAA development and rupture to develop new therapies. In this review, we summarize animal TAA models including recent developments in porcine and zebrafish models: porcine models can assess new therapeutic devices or intervention strategies in a large mammal and zebrafish models can employ large-scale small-molecule suppressor screening in microwells. The second part of the review covers current views of TAA pathogenesis, with a focus on the roles of the transforming growth factor-beta (TGFβ) pathway and the vascular smooth muscle cell (VSMC)-elastin-contractile unit. The last part discusses TAA treatment options as they emerge from recent preclinical studies.

Although cancer care is often contextualized in terms of survival, there are other important cancer care outcomes, such as quality of life and cost of care. The ASCO Value Framework assesses the value of cancer therapies not only in terms of survival but with consideration of quality of life and financial cost. Early palliative care for patients with advanced cancer is associated with improved quality of life, mood, symptoms, overall survival, and cost savings. While palliative care has been shown to have numerous benefits, the impact of real-world implementation of outpatient embedded palliative care on value-based metrics is not fully understood. We sought to describe the association of outpatient embedded palliative care in a multidisciplinary thoracic oncology clinic on inpatient value-based metrics. We performed a retrospective cohort study of 215 patients being treated for advanced thoracic malignancies with non-curative intent. We evaluated the association of outpatient embedded palliative care with inpatient clinical outcomes including emergency room visits, hospitalizations, intensive care unit admissions, hospital charges, as well as hospital quality metrics including 30-day readmissions, admissions within 30 days of death, inpatient mortality, and inpatient hospital charges. Outpatient embedded palliative care was associated with lower hospital charges per day ($3,807 versus $4,695, p=0.024). Furthermore, patients who received outpatient embedded palliative care had decreased hospital admissions within 30 days of death (O.R. 0.50; 95% CI 0.34, 0.74; P<0.001) and decreased inpatient mortality (O.R. 0.46; 95%CI 0.23, 0.94; p=0.032). Our study further supports that outpatient palliative care is a high-value intervention and alternative models of palliative care, including one embedded into a multidisciplinary thoracic oncology clinic, is associated with improved value-based metrics.

Epoxy matrix composites reinforced with high-performance fibers such as carbon, Kevlar, and glass, exhibit excellent specific stiffness and strength in many mechanical applications. However, these composites are disappointingly non-recyclable and are usually disposed of in landfill sites, with no realistic prospect for biodegradation in reasonable time. In contrast, moldable composites with carbonized elastomeric matrices developed in the last decades possess attractive mechanical properties in final net-shape products and can also be incinerated or recycled. Many carbon and inorganic fillers have recently been evaluated to adjust the properties of carbonized elastomeric composites. Renewable organic fillers such as human or animal hair offer an attractive fibrous material with substantial potential for reinforcing composites with elastomeric matrices. Samples of unidirectional fiber composites (with hair volume fraction up to 7 %) and quasi-isotropic short fiber composites (with hair volume fraction up to 20 %) of human hair-reinforced nitrile butadiene rubbers (HH-NBR) were produced in the peroxide-cured and carbonized states. The samples were characterized using SEM, Raman spectroscopy and photoacoustic microscopy. Mechanical tests were performed in tension using a miniature universal testing machine. The expected effect of fiber reinforcement on the overall mechanical performance has been demonstrated for both cured and carbonized composites. Considerable enhancement of the elastic modulus (up to 10 times), ultimate tensile strength (up to 3 times) and damage tolerance was achieved. The evidence of satisfactory interfacial bonding between hair and rubber was confirmed by SEM imaging of fracture surfaces. The suitability of photoacoustic microscopy was assessed for 3D reconstruction of the fiber sub-system spatial distribution and non-destructive testing.

Self-adaptive systems are capable of reconfiguring themselves while in use to reduce the risks forced by environments for which they may not have been specifically designed. Run-time validation techniques are required because complex Self-adaptive systems must consistently offer acceptable behavior for important services. The run-time testing can offer further confidence that a Self-adaptive system will continue to act as intended even when operating in unknowable circumstances. This article introduces an evolutionary framework that supports adaptive testing for Self-adaptive systems. To ensure that the adaptive systems continue to operate following its requirements and that both test plans and test cases continuously stay relevant to shifting operational conditions. The proposed approach using the SPEA2 algorithm facilitates both the execution and adaptation of run-time testing operations.

An experiment was conducted in 2016 & 2017 for development of novel rice hybrids for aerobic ecology with lesser yield penalties in comparison to irrigated ecosystem, further with added advantage of reduced methane emissions and water budget as witnessed in irrigated system. Based on the restorer / maintainer reaction and spikelet fertility (%), 10 restorer lines were selected to cross with 3 CMS lines in the line by tester fashion in Yasangi (summer) season 2016-17. Resulting 30 experimental hybrids besides 13 parental lines (10 Restorer lines and 3 B - lines of akin CMS lines) and checks (GK 5022, CR Dhan 201) assessed during Vankalam (rainy) season 2017 at three different places/locations viz., Rajendranagar, Warangal and Kampasagar. The outcome of experiment were two experimental hybrids viz., APMS-6A × HRSV – 7 and IR-79156A × ATR – 372, were categorized as stable hybrids with desirable sca effects, heterosis (ranging from 7% to 13%) over best check GK 5022 along with an in-essence performance for yield and other yield attributing characters.

Treatment of the [AuCl(tetrahydrothiophene)] complex with 4-chloro-2-iodo-1-isocyanobenzene furnished the gold(I) compound [AuCl(CNC6H3-4-Cl-2-I)] (1). In the crystal structure of 1, the linear C–Au–Cl group is subject to the solid-state head-to-tail pairing which is determined by the aurophilic Au···Au and the rare π-holeCN···Cl interactions. These two types of structure-determining interactions are complementary to each other and the system of Au···Au and CCN···Cl contacts accomplishes 2D extended ladder-type architecture. In addition, the terminal I-atoms are involved in the three-center halogen bonding. Density functional theory calculations, employing a set of computational tools, verified the role of Au···Au and π-holeCN···Cl noncovalent bonds in the spectrum of noncovalent forces.

In the present study, the ability of novel carbon microspheres (CMs) derived from a date palm (Phoenix dactylifera) biomass using a hydrothermal carbonization (HTC) process and activated using phosphoric acid in removing methylene blue dye was investigated. Three types of palm-based wastes (seeds, leaflet and inedible crystallized date palm molasses) were used and converted to CMs via HTC process. The prepared samples were then activated using phosphoric acid via incipient wetness impregnation method. The CMs samples before and after activation were analyzed using scanning electron microscopy (SEM), elemental analysis and scanning (CHNS), Fourier Transform-Infrared (FTIR) and Brunauer–Emmet–Teller (BET) method. The samples exhibited high BET surface areas after activation (1,584 m2/g). The methylene blue adsorption results showed good fittings to the Langmuir and Redlich-Peterson isotherm models for all activated samples. The maximum adsorption capacity achieved was 409.84 mg/g for activated CM obtained from the palm date molasses, indicating high potential for application as dye-based adsorption materials.

Two-stage surgery is unintentionally necessary when total tumor removal cannot be accomplished in the first surgery, although, it has not yet been established how to leave the tumor for the next surgery. There is a risk of postoperative hemorrhage in the residual tumor, especially in hypervascular tumors. We report a case of hypervascular choroid plexus papilloma in which preservation of intratumoral venous drainage was considered important to avoid hemorrhagic complications during a two-stage surgery. In hypervascular tumor resection, to prevent postoperative hemorrhage associated with a residual tumor, it may be important to preserve venous drainage of the tumor.

Currently, software development is more associated with families of configurable software rather than the single implementation of a product. Due to the numerous possible combinations in a software product line, testing these families of software product lines (SPLs) is a difficult undertaking (SPL). Moreover, the presence of optional features makes the testing of SPLs impractical. Several features are presented in SPLs, but due to the environment's time and financial constraints, these features are rendered unfeasible. Testing subsets of configured products is thus one approach to solving this issue. In order to reduce testing effort and get better results, alternative methods of testing SPLs are required, such as the combinatorial interaction testing (CIT) technique. Unfortunately CIT method produces unscalable solutions for large size SPLs with excessive constraints. The CIT method costs more because of feature combinations. The optimization of the various conflicting testing objectives, such as reducing the cost and configuration number, have also been considered. In this article, we have proposed a search-based software engineering solution using multi-objective optimization algorithms (MOEAs). In particular, the research is applied to different types of MOEA methods; Indicator-Based Evolutionary Algorithm (IBEA), Multi-objective Evolutionary Algorithm based on Decomposition (MOEA/D), Non-Dominated Sorting Genetic Algorithm II (NSGAII), NSGAIII, and Strength Pareto Evolutionary Algorithm 2 (SPEA2). The results of the algorithms are examined in the context of distinct objectives and two quality indicators. The results revealed how feature model attributes, implementation context and the number of objectives affect the performance of the algorithms.

As the major greenhouse gas, CO2 gas emission has been noticeably increased over the past decades resulting in global warming and climate change. As a result, it is imperative to reduce the excess CO2 in the atmosphere to hold “the increase in the global average temperature to well below 2°C (ideally 1.5°C) above pre-industrial levels set by the Paris Agreement on climate change. Among many ways, CO2 capture technology is considered as the most promising technology among the available technologies. Porous materials such as carbons, silica, zeolites, hollow fibers, and alumina are widely used as CO2 sorbents. However, among the available porous sloid sorbents, porous silica-based materials grabbed a significant attention due to their unique properties including high surface area, pore volume, good thermal and mechanical stability, and low cost. Therefore, development of porous silica materials as a promising CO2 absorbent is a continuously expanding research area in the current moment. Herein, we aim to visualize a full picture of the porous silica-based materials for CO2 capture. This review presents a comprehensive study of existing CO2 capture techniques and highlights the recent progress of different porous silica materials and synthesis processes. CO2 adsorption capacities of unmodified porous silica materials are less effective as compared with functionalized silica materials. Various research activities have been reported about functionalization of pours silica using amine groups. Therefore, in this review, different synthesis routes of amine-functionalized porous silica materials, CO2 adsorption capacities, gas selectivity and reusability were discussed. Moreover, the research challenges associated with the porous silica materials and future research directions are summarized.

This study describes a comparative in vitro study of the toxicity behavior of zinc oxide (ZnO) nanoparticles and micro-sized particles. The study aimed to understand the impact of particle size on ZnO toxicity by characterizing the particles in different media, including cell culture media, human plasma, and protein solutions (bovine serum albumin and fibrinogen). The study used various techniques such as atomic force microscopy (AFM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) to characterize the particles and their interactions with proteins. Hemolytic activity, coagulation time, and cell viability assays were used to assess ZnO toxicity. The results highlight the complex interactions between ZnO NPs and biological systems, including their aggregation behavior, hemolytic activity, protein corona formation, coagulation effects, and cytotoxicity. Moreover, the study indicates that ZnO nanoparticles are not more toxic than micro-sized particles, and the 50 nm particles resulted in general the least toxic. Furthermore, the study found that at low concentrations, no acute toxicity was observed. Overall, this study provides important insights into the toxicity behavior of ZnO particles and highlights that no direct relationship between nanometer size and toxicity can be directly attributed.

The processes of the sublimation and thermal decomposition of the 1‐ethyl‐3‐methylimidazolium hexafluorophosphate ionic liquid (EMImPF6) were studied by a complex approach including Knudsen effusion mass spectrometry, IR and NMR spectroscopy, and quantum chemical calculations. It was established that the vapor over liquid phase primarily consists of decomposition products under equilibrium conditions. Otherwise, the neutral ion pairs are the only vapor components under Langmuir conditions. To identify the nature of the decomposition products an experiment on the distillation of the ionic liquid was performed and the collected distillate was analyzed. It was revealed by the IR and NMR spectroscopy that EMImPF6 decomposes to substituted imidazole‐2‐ylidene (C6N2H10PF5) and HF. The measured vapor pressure of C6N2H10PF5 reveals a very low activity of the decomposition products (&lt;10–4) in the liquid phase. The absence of significant accumulation of decomposition products in the condensed phase makes it possible to determine the enthalpy of sublimation of the ionic liquid assuming its unchanged activity. The thermodynamics of the EMImPF6 sublimation was studied by Knudsen effusion mass spectrometry. The formation enthalpy of EMImPF6 in ideal gas state was found from combination of the sublimation enthalpy and formation enthalpy of ionic liquid in the condensed state. The obtained value is in good agreement with those calculated by quantum chemical methods.

This work demonstrated the potential of CNC as a substitute for PEG as an additive in ultrafiltration membrane fabrication. Two sets of modified membranes were fabricated using the phase inversion technique with polyethersulfone (PES) as the base polymer, and 1-N-methyl-2 pyrrolidone (NMP) as the solvent. The first set was fabricated with 0.075 wt% CNC, while the second set was fabricated with 2 wt% PEG. All membranes were characterized using SEM, EDX, FTIR, and contact angle measurements. The SEM images were analyzed for surface characteristics using WSxM 5.0 Develop 9.1 software. The membranes were tested, characterized, and compared for their performance in treating both synthetic turbid water and real restaurant Both membranes exhibited improved hydrophilicity, morphology, pore structure, and roughness. Both membranes also exhibited similar water flux for real and synthetic polluted water. However, the membrane prepared with CNC gave the higher turbidity removal and COD removal when raw restaurant water was treated. The membrane compared well with the UF membrane containing 2 wt% PEG in terms of morphology and performance when synthetic turbid water and raw restaurant water were treated.

The study aims to investigate Gen Z's intentions to utilize the Waze mobile application as a solution for sustainable traffic management in Meto Manila. The extended Technology Acceptance Model (TAM) was used to define user behavior and technology usage to determine the factors influencing Filipino drivers' application acceptance of Waze. The study’s data results have revealed that the System Quality, Perceived Location Accuracy, Perceived Usefulness, and Perceived Ease of Use affect Filipinos' intentions to use traffic navigation applications, particularly Waze. The study utilized a survey and was given to 300 Filipino drivers traveling within the National Capital Region to accurately measure the factors and their connections to usage intention and actual use. The analytical approach used for this investigation was partial least squares structural equation modeling (PLS-SEM). The study's results can be applied as a theoretical framework for future researchers of Waze mobile applications, Waze route accuracy, and Waze overall application performance, as well as the features of the Waze application, to evaluate how the use of the Waze mobile application could help in the effective management of traffic situations in Metro Manila. The study was able to assess the effectiveness of the Waze navigation app as a platform for efficiently managing traffic situations in Metro Manila. Moreover, this study also highlighted the application performance of Waze and its acceptance by Filipino drivers in Metro Manila. Furthermore, the study implores a critical review of Waze's application performance. The study recommends that similar future studies must consider samples from a more diverse geographic background to obtain a more accurate representation of Filipinos traveling. Future researchers are also advised to adopt a qualitative research design to gain more detailed insights of Filipinos regarding their experience with the Waze application.

The ultimate objective of this research work is to design a sensitive and selective electrochemical sensor for efficient detection of ascorbic acid (AA), a vital antioxidant found in blood serum that may serve as a biomarker for oxidative stress. To achieve this, we utilized a novel Yb2O3.CuO@rGO nanocomposite (NC) as the active material to modify the glassy carbon working electrode (GCE). The structural properties and morphological characteristics of the Yb2O3.CuO@rGO NC were investigated using various techniques to ensure their suitability for the sensor. The resulting sensor electrode was able to detect a broad range of AA concentrations (0.5 - 1571 µM) in neutral phosphate buffer solution with a high sensitivity of 0.4341 µAµM-1cm-2 and a reasonable detection limit of 0.062 µM. The sensor's great sensitivity and selectivity allowed it to accurately determine the levels of AA in human blood serum and commercial vitamin C tablets. It demonstrated high levels of reproducibility, repeatability, and stability, making it a reliable and robust sensor for the measurement of AA at low overpotential. Overall, the Yb2O3.CuO@rGO/GCE sensor showed great potential in detecting AA from real samples.

Commonly employed methods for reversibly disrupting gene expression, such as those based on RNAi or CRISPRi, are rarely capable of achieving >80-90% downregulation, making them unsuitable for targeting genes that require more complete disruption to elicit a phenotype. Genetic deletion, on the other hand, while enabling complete disruption of target genes, often produces undesirable irreversible consequences such as cytotoxicity or cell death. Here we describe the design, development and detailed characterization of a dual-function "TRE-Lox" system for effecting either (a) doxycycline (Dox)-mediated downregulation or (b) genetic deletion of cathepsin D (CatD), based on targeted insertion of a tetracycline-response element (TRE) and two LoxP sites into the 5' end of the endogenous gene (CTSD). Using an optimized reverse-tetracycline transrepressor (rtTR) variant fused with the Krüppel-associated box (KRAB) domain, we show that CatD expression can be disrupted by as much as 98% in mouse embryonic fibroblasts (MEFs). This system is highly sensitive to Dox (IC50 = 1.46 ng/mL) and results in rapid (t1/2 = 0.57 d) and titratable downregulation of CatD. Notably, even near-total disruption of CatD expression was completely reversed by withdrawal of Dox. As expected, transient expression of Cre recombinase results in complete deletion of the CTSD gene. The dual functionality of this novel system will facilitate future studies of the involvement of CatD in various diseases, particularly those attributable to partial loss of CatD function. In addition, the TRE-Lox approach should be applicable to the regulation of other target genes requiring more complete disruption than can be achieved by traditional methods.

Bacterial nitroreductase enzymes that convert prodrugs to cytotoxins are valuable tools for creating transgenic targeted ablation models to study cellular function and cell-specific regeneration paradigms. We recently engineered a nitroreductase (“NTR 2.0”) for substantially enhanced reduction of the prodrug metronidazole, which permits faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms useful for modelling chronic diseases. To provide insight into the enhanced enzymatic mechanism of NTR 2.0, we have solved the X-ray crystal structure at 1.85 Angstroms resolution and compared it to the parental enzyme, NfsB from Vibrio vulnificus. We additionally present a survey of reductive activity with eight alternative nitroaromatic substrates, to provide access to alternative ablation prodrugs, and explore applications such as remediation of dinitrotoluene pollutants. The predicted binding modes of four key substrates were investigated using molecular modelling.

Downward short-wave (SW) solar radiation is the only essential energy source powering the atmospheric dynamics, ocean dynamics, biochemical processes, etc. on our planet. Clouds are the main factor limiting the SW flux over the land and the Ocean. For the accurate meteorological measurements of the SW flux one needs expensive equipment - pyranometers. For some cases where one does not need golden-standard quality of measurements, we propose estimating incoming SW radiation flux using all-sky optical RGB imagery which is assumed to incapsulate the whole information about the SW flux. We used DASIO all-sky imagery dataset with corresponding SW downward radiation flux measurements registered by an accurate pyranometer. The dataset has been collected in various regions of the World Ocean during several marine campaigns from 2014 to 2022, and it will be updated. We demonstrate the capabilities of several machine learning models in this problem, which are multilinear regression, Random Forests, Gradient Boosting and convolutional neural networks (CNN). We also applied the inverse target frequency (ITF) re-weighting of the training subset and the approach of pre-classification in order to raise the SW flux approximation quality. We found that the CNN is capable of approximating downward SW solar radiation with higher accuracy compared to existing empiric parameterizations. We also found that the ITF reweighting of the training subset increases the approximation quality substantially. The estimates of the SW radiation flux using all-sky imagery may be of particular use in case of the need for the fast radiative budgets assessment of a site.

Generalized relativistic pseudopotentials (GRPP) of atomic cores implying the use of different potentials for atomic electronic shells with different principal quantum numbers give rise to accurate and reliable relativistic electronic structure models of atoms, molecules, clusters, and solids. These models readily incorporate the effects of Breit electron-electron interactions and one-loop quantum electrodynamics effects. Here we report the computational procedure for evaluating one-electron integrals of GRPP over contracted Gaussian functions. This procedure was implemented in a library of routines named LIBGRPP, which can be integrated into existing quantum chemistry software, thus enabling the application of various methods to solve the many-electron problem with GRPPs. Pilot applications to electronic transitions in the ThO and UO2 molecules using the new library and intermediate-Hamiltonian Fock space relativistic coupled cluster method are presented. The results clearly demonstrate that rather economical tiny-core GRPP models can exceed in accuracy relativistic all-electron models defined by Dirac-Coulomb and Dirac-Coulomb-Gaunt Hamiltonians.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

Cryopreservation has been used extensively for cattle in Bangladesh, albeit no study was conducted on the cryopreservation techniques of buffalo. This study compares two freezing methods and the effects of diluters on the semen quality of buffalo. In the first freezing protocol, semen was frozen in two-step: from 37 °C to 5 °C for 30 minutes in a BLRI-developed equilibration chamber and from 5 oC to -120 oC in a Styrofoam box using liquid nitrogen vapor from different distances (0.5, 1.5, 1.6, 2 and 3 inches). At the same time semen was frozen in a programmable freezer in three steps. The semen samples were then evaluated for motility and morphological quality by CASA. In another experiment, the efficacy of one locally developed diluter-Tris-fructose-egg yolk-based (TFE) and three commercial diluters (Andromed, Triladyl and Steridyl) were evaluated. The highest number of motile sperms (62.67±1.12; P< 0.01) and progressive motility (38.97±1.10; P < 0.001) was observed at 1.6 inches above liquid nitrogen. There was no significant difference in overall motility, progressive and slow motility between semen cryopreserved in the cheap nitrogen vapor technique (57.49±5.67, 38.70± 4.04 and 3.83± 0.63, respectively) and expensive automated technique (65.94±4.65, 45.54 ± 3.64 and 2.43± 0.36, respectively). The highest recovery rate and conception rate were observed in semen diluted with TFE (82.4% and 80%, respectively). Hence, the cryopreservation technique using nitrogen vapor and TFE diluent is cost-effective and suitable for freezing buffalo semen that would produce superior semen for artificial insemination.

Short Linear Motifs (SLiMs) are short linear sequences that can mediate protein-protein interaction. Mimicking eukaryotic SLiMs to compete with extra or intracellular binding partners or to sequester host proteins is the crucial strategy of viruses to pervert the host system. The evolved proteins in viruses facilitate minimal protein-protein interactions that significantly affect intracellular signaling networks. Unfortunately, very little information about the SARS-CoV-2 SLiMs is known, especially across the SARS-CoV-2 variants. Through ELM database-based sequence analysis of spike protein from all the major SARS-CoV-2 variants, we identified four overriding SLiMs in the SARS-CoV-2 Omicron variant including LIG_TRFH_1, LIG_REV1ctd_RIR_1, LIG_CaM_NSCaTE_8, and MOD_LATS_1. These SLiMs are highly likely to interfere with various immune functions, interact with host intracellular proteins, regulate cellular pathways, and lubricate viral infection and transmission. These cellular interactions possibly serve as potential therapeutic targets for these variants, and this approach can be further exploited to combat emerging SARS-CoV-2 variants.

Genomics has put prokaryotic rank-based taxonomy on a solid phylogenetic foundation. However, most taxonomic ranks were set long before the advent of DNA sequencing and genomics. In this concept paper, we thus ask the simple yet profound question: Should prokaryotic classification schemes besides the current phylum-to-species ranks be explored, developed, and incorporated into scientific discourse? Could such alternative schemes provide better solutions to the basic need of science and society for which taxonomy was developed, namely, precise and meaningful identification? A neutral genome-similarity based framework is then described that could allow alternative classification schemes to be explored, compared, and translated into each other without having to choose only one as the gold standard. Classification schemes could thus continue to evolve and be selected according to their benefits and based on how well they fulfill the need for prokaryotic identification.

TP53 is a tumor suppressor gene that encodes a sequence-specific DNA-binding transcription factor activated by stressful stimuli and upregulates target genes involved in growth suppression, cell death, DNA repair, metabolism, among others. P53 is the most frequently mutated gene in tumors with mutations not only leading to loss-of-function (LOF), but also gain-of-function (GOF) which promotes tumor progression, and metastasis. The tumor-specific status of mutant p53 protein has suggested it is a promising target for cancer therapy. We summarize the current progress of targeting wild-type and mutant p53 for cancer therapy through biotherapeutic and biopharmaceutical methods for 1) boosting p53 activity in cancer, 2) p53-dependent and p53-independent strategies for targeting p53 pathway functional restoration in p53-mutated cancer, 3) targeting p53 in immunotherapy, and 4) combination therapies targeting p53, p53 checkpoints, or mutant p53 for cancer therapy.