The primary screening of hybridoma cells is a time-critical and laborious step during the development of monoclonal antibodies. Often critical errors occur in this phase, which supports the notion that the generation of monoclonal antibodies with hybridoma technology is difficult to control and hence a risky venture. We think that it is crucial to improve the screening process to eliminate most of the immanent deficits of the conventional approach. With this new microarray-based procedure, several advances could be achieved: Selectivity for excellent binders, high throughput, reproducible signals, avoidance of misleading avidity (multivalency) effects, and simultaneous performance of competition experiments. The latter can directly be used to select clones of desired cross-reactivity properties. In this paper, a model system with two excellent clones against carbamazepine, two weak clones and blank supernatant has been designed to examine the effectiveness of the new system. The excellent clones could be detected largely independent of the IgG concentration, which is unknown during the clone screening since the determination and subsequent adjustment of the antibody concentration is not possible in most cases. Furthermore, in this approach, the enrichment, isolation, and purification of IgG for characterization is not necessary. Raw cell culture supernatant can be used directly, even when fetal calf serum (FCS) or other complex media had been used. In addition, an improved method for the oriented antibody-immobilization on epoxy-silanized slides is presented. Based on the results of this model system, we conclude that this approach should be preferable to most other protocols leading to many of false positives, causing expensive and lengthy confirmation steps to weed out the poor clones.

Additive manufacturing (AM) or 3D printing is a promising industrial technology that enables rapid prototyping of complex configurations. Powder Bed Fusion (PBF) is one of the most popular AM techniques for metallic materials. Until today, only a few metals and alloys are available for AM, e.g. titanium alloys, the most common of which is Ti-6Al-4V. After optimization of the PBF parameters, with or without post processing such as heat treatment or hot isostatic pressing, the printed titanium alloy can easily reach tensile strengths of over 1100 MPa due to the quickly cooling of AM process. However, attributed to the unique features of metallurgical defects and microstructure introduced by this AM process, their fatigue strength has been low, often only not less than 30% of the tensile strength, especially in very-high-cycle regime, i.e. failure life beyond 107 cycles. Here, we have reviewed the current state of research on the very-high-cycle fatigue (VHCF) of additively manufactured (AMed) titanium alloys, refined the basic quantities of AMed microstructure and metallurgical defects, summarized the main factors limiting their VHCF strengths, and suggested possible ways to improve VHCF performance.

Polyetheretherketone is a promising material for implants due to its good mechanical properties and excellent biocompatibility. Its accessibility to a wide range of applications is facilitated by the ability to process it with an easy-to-use manufacturing process such as Fused Filament Fabrication. The elimination of disadvantages associated with the manufacturing process, such as a poor surface quality, is a main challenge to deal with. As part of the mass finishing process, centrifugal disc finishing has demonstrated good results in surface optimization, making it a promising candidate for post-processing of additively manufactured parts. The objective of this study is to identify the key parameters of the centrifugal disc finishing process on the waviness of additively manufactured PEEK specimen, which has not been investigated yet. Waviness of the specimen was investigated by means of confocal laser scanning microscopy (CLSM), while weight loss was additionally tracked. Six parameters were investigated: type, amount and speed of media, use of compound, amount of water and time. Type of media, time and speed were found to significantly influence waviness reduction and weight loss. Surface electron microscopy images demonstrated the additional effects of deburring and corner rounding. Results on previous studies with specimens made of metal showed similar results. Further investigation is required to optimise waviness reduction and polish parts in a second post-processing step.

A general procedure is described, to generate material parameter sets to simulate fire propagation in horizontal cable tray installations. Cone Calorimeter test data is processed in an inverse modelling approach. Here, parameter sets are generated procedurally and serve as input for simulations conducted with the Fire Dynamics Simulator (FDS). The simulation responses are compared with the experimental data and ranked based on their fitness. The best fitness was found for a test condition of \SI{50}{\kilo\watt\per\meter^2}. Low flux conditions \SI{25}{\kilo\watt\per\meter^2} and less exhibited difficulties to be simulated accurately. As a validation step, the best parameter sets are then utilised to simulate fire propagation within a horizontal cable tray installation and are compared with experimental data. It is important to note, the inverse modelling process is focused on the Cone Calorimeter and not aware of the actual validation step. Despite this handicap, the general features in the fire development can be reproduced, however not exact. The fire in the tray simulation extinguishes earlier and the total energy release is slightly higher as compared to the experiment. The responses of the material parameter sets are briefly compared with a selection of state of the art procedures.

The generation of isogenic induced pluripotent stem cell (iPSC) lines using CRISPR-Cas9 technology is a technically challenging, time-consuming process with variable efficiency. Here we use fluorescence-activated cell sorting (FACS) to sort biallelic CRISPR-Cas9 edited single-cell iPS clones into high-throughput 96-well microtiter plates. We used high-content screening (HCS) technology and generated an in-house developed algorithm to select the correctly edited isogenic clones for continued expansion and validation. In our model we have gene-corrected the iPSCs of a Parkinson’s disease (PD) patient carrying the autosomal dominantly inherited heterozygous c.88G>C mutation in the SNCA gene, which leads to the pathogenic p.A30P form of the alpha-synuclein protein. Undertaking a PCR restriction-digest mediated clonal selection strategy prior to sequencing, we were able to post-sort validate each isogenic clone using a quadruple screening strategy. Subsequent transfection with mRNA encoding excision-only transposase allows for the generation of footprint-free isogenic iPSC lines. These monoclonal isogenic iPSC lines retain a normal molecular genotype, express pluripotency markers and have the ability to differentiate into the three germ layers. This combinatory approach of FACS, HCS and post-sorted restriction digestion facilitates the generation of isogenic cell lines for disease modelling to be scaled-up on an automated platform.

Three-dimensional (3D) printing technologies are transforming the design and manufacture of components and products across a variety of disciplines, however their application in the construction industry is still limited. Material deposition processes can achieve infinite geometries and have advanced from rapid prototyping and model-scale markets to their application in fabricating functional products, large objects and the construction of full-scale buildings. Many international projects have recently been realized and the construction industry is beginning to utilise these dynamic technologies. The potential advantages for integrating 3D printing into house construction are significant, these include the capacity for mass customization of designs and parameters for functional and aesthetic purposes, reduction in construction waste from highly precise material placement, and the use of recycled waste products in layer deposition materials. With the ultimate goal of improving construction efficiency and decreasing building costs, applying Strand7 Finite Element Analysis software, a numerical model was designed specifically for 3D printing in a cement mix incorporated with recycled waste product High Density Polyethylene (HDPE) and found that construction of an arched truss-like roof was structurally feasible without the need for steel reinforcements. The lab sizes prototypes were manufactured based on the destined numerical model by using a 3D printing technology. Currently available 3D printing technologies can be adopted for building construction and this paper discusses the applications, advantages, limitations and future directions of 3D printing as an innovative and viable solution for affordable house construction.

During middle age, women are less susceptible to nonalcoholic steatohepatitis (NASH) than men. Thus, we investigated the underlying molecular mechanisms behind these sexual differences using an established rat model of NASH. Mature female and male stroke-prone spontaneously hypertensive 5/Dmcr rats were fed control or high-fat-cholesterol (HFC) diets for 2, 8, and 14 weeks. Although HFC-induced hepatic fibrosis was markedly less severe in females than in males, only minor gender differences were observed in expression levels of cytochrome P450 enzymes (CYP)7A1, CYP8B1 CYP27A1, and CYP7B1, and multidrug resistance-associated protein 3, and bile salt export pump, which are involved in fibrosis-related bile acid (BA) kinetics. However, the BA detoxification-related enzymes UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) 2A1, and the nuclear receptors constitutive androstene receptor (CAR) and pregnane X receptor (PXR), were strongly suppressed in HFC fed males, and were only slightly changed in HFC-diet fed females. Expression levels of the farnesoid X receptor and its small heterodimer partner were similarly regulated in a gender-dependent fashion following HFC feeding. Hence, the pronounced female resistance to HFC-induced liver damage likely reflects sustained expression of the nuclear receptors CAR and PXR and the BA detoxification enzymes UGT and SULT.

The classification of Trojans in modern analog microcircuits is considered. Using high-speed operational amplifiers (Op-Amps) as an example, the relationship between Op-Amp circuit design and the formation of undesirable states in typical switching circuits is shown. Circuit solutions are proposed to minimize the Trojan states of high-speed Op-Amps. These include limiting the maximum output currents of the input stages of the Op-Amp during the transient process and the use of differentiating transient correction circuits in the Op-Amp.

Melting phase relations of the diamond-forming system olivine (Ol) – jadeite (Jd) – diopside (Di) – (Mg, Fe, Ca, Na)-carbonates (Carb*) – (C-O-H-fluid) are studied in experiments at 6.0 GPa in the polythermal section Ol74Carb*18.5(C-O-H)7.5 - Omp74Carb*18.5(C-O-H)7.5, where Ol = Fo80Fa20, Omp (omphacite) = Jd62Di38 and Carb* = (MgCO3)25(FeCO3)25(CaCO3)25(Na2CO3)25. Peritectic reaction of olivine and jadeite-bearing melt with formation of garnet has been determined as a physico-chemical mechanism of ultrabasiс-basiс evolution of the diamond-forming system. In the process CO2-component of the supercritical C-O-H-fluid can react with silicate components to form additional carbonates of Mg, Fe, Ca and Na. Solidus temperature of the diamond-forming system is depressed to 1000-1020°C by joint effect of the H2O-fluid and carbonate constituents thereof. The experimentally recognized peritectic mechanism of ultrabasiс-basiс evolution of the diamond-forming system explains the origin of the associated paragenetic inclusions of peridotite and eclogite minerals in diamonds as well as the xenoliths of diamond-bearing peridotites and eclogites of the kimberlitic deposits of diamond. The diamond-forming systems have formed with the use of material of the upper mantle native peridotite rocks. In this case the capacity of the rocks to run the peritectic reaction of olivine was transmitted with silicate components to the diamond-forming systems.

The glucocorticoid receptor alpha (GRα), a pivotal component of the ancient glucocorticoid (GC) signaling system that emerged nearly 450 million years ago, has been instrumental in directing vertebrate evolution and is essential for survival, regulating fertility and fetal development, the function of every organ and circulating cells, metabolism, immune responses, and adaptation to stress. While its anti-inflammatory properties have been recognized since the mid-20th century, GRα’s broader role as the master regulator of homeostatic corrections, particularly in health and critical illness, has only recently been fully appreciated.GRα orchestrates three key phases of homeostatic correction: the Priming Phase, where it rapidly activates early immune responses, mobilizes energy reserves, and prepares the body to mount an immediate defense against various physiological stressors, including infection and injury. During this phase, GRα enhances glucose metabolism, supports mitochondrial function, and facilitates the release of key immune cells to the site of damage, ensuring the body is equipped to handle the initial assault. The Modulatory Phase follows, in which GRα fine-tunes the inflammatory response to prevent excessive tissue damage. By balancing pro- and anti-inflammatory signals, GRα helps contain the immune response, preventing the harmful effects of prolonged inflammation while maintaining immune surveillance. This phase also involves the regulation of oxidative stress, vascular tone, and the preservation of cellular integrity to protect vital organs from injury. Finally, in the Restorative Phase, GRα plays a critical role in resolving inflammation and initiating tissue repair. During this phase, GRα supports cellular regeneration, promotes the clearance of apoptotic cells and debris, and restores anatomical and physiological balance. It aids in rebuilding tissue architecture and returning the neuroendocrine-immune system to its baseline state, ensuring long-term recovery and stability.Throughout these phases, GRα manages complex interactions, including recently discovered co-regulation with pro-inflammatory transcription factors, while also regulating mitochondrial function to ensure bioenergetic and metabolic stability during stress. In critically ill patients, depletion of bioenergetic and micronutrient reserves severely impairs GRα’s capacity to regulate immune responses, heightening the risk of morbidity and mortality.This review, in light of this new understanding, underscores the need to re-evaluate current glucocorticoid (GC) treatment strategies, emphasizing the incorporation of micronutrient support to optimize GRα function across all phases of homeostatic correction. This integrated therapeutic approach has the potential to enhance both immediate immune responses and long-term recovery in critically ill patients, offering a more comprehensive strategy for managing the complex pathobiology of critical illness. Furthermore, this integrative approach could decrease glucocorticoid dose and duration requirements and potential side effects.

High temperature (HT) geothermal wells can provide green power 24h a day 7 days a week. Harsh environmental and operational conditions, long-term durability requirements of such wells require special cementitious composites for well construction. This paper reports a comprehensive assessment of geothermal cement composites in cyclic pressure function laboratory tests, field exposures in an HT geothermal well (300-350oC) as well as a numerical model to complement the experimental results. Performances of calcium-aluminate-cement (CAC)-based composites and calcium free cement were compared against reference Ordinary Portland Cement (OPC)/silica blend. The stability and degradation of the tested materials was characterized by crystalline composition, thermo-gravimetric, and elemental analyses, morphological studies, water-fillable porosity, and mechanical properties measurements. All CAC-based formulations outperformed the reference blend both in the function and exposure tests. The reference OPC/silica lost its mechanical properties during the 9-month well exposure through extensive HT carbonation, while properties of the CAC-based blends improved over that period. The Modified Cam-Clay (MCC) plasticity parameters of several HT cement formulations were extracted from triaxial and Brazilian tests and verified against the experimental results of function cyclic tests. These parameters can be used in well integrity models to predict field-scale behavior of the cement sheath under geothermal well conditions.

Engineering application of additively manufactured (AM) metallic materials is quite limited by their fatigue behaviors which are very inconsistent with that of conventionally wrought or cast ones. Here, based on advanced material characterization techniques, such as focused ion beam (FIB), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), the mi-crostructures underneath fracture surfaces were thoroughly investigated in an AM aluminium (AlSi10Mg) alloy with horizontal and vertical building orientation endured very-high-cycle fa-tigue (VHCF) loading under stress ratios R = –1, 0 and 0.5. Two VHCF failure specimens A and B were representatively selected to further SEM examine and TEM samples preparation via FIB milling. Specimen A was horizontally printed and failed at R = –1; specimen B was vertically printed and failed at R = 0. TEM samples A1 and B1 were lifted from locations near the crack ini-tiation sites on the fracture surfaces of specimens A and B; The locations of TEM samples A2 and B2 kept away from the crack origin sites but still within the “fish-eye” region of crack steady growth. TEM observations show that there was no characteristic microstructure induced by VHCF in different oriented specimens and under various R values.

This paper attempts to develop a Dynamic Mode Decomposition (DMD) based Reduced Order Model (ROMs) which can quickly but accurately predict the forces and moments experienced by a road vehicle such that they be used by an on-board controller to determine the vehicle's trajectory. DMD can linearize a large dataset of high-dimensional measurements by decomposing them into low-dimensional coherent structures and associated time-dynamics. This ROM then also can be applied to predict the future state of the fluid flow. Existing literature on DMD is limited to low Reynolds number applications. This paper presents DMD analyses of the flow around an idealized road vehicle, called the Ahmed body, at a Reynolds number of 2.7E6. The high dimensional dataset used in this paper was collected from a computational fluid dynamics (CFD) simulation performed using Menter's shear stress transport (SST) turbulence model within the context of Improved Delayed Detached Eddy Simulations (IDDES). The DMD algorithm, as available in literature, was found to suffer nonphysical dampening of the medium-to-high frequency modes. Enhancements to the existing algorithm were explored, and a modified DMD approach is presented in this paper which includes: (a) a requirement of higher sampling rate to obtain higher resolution of data, and (b) a custom filtration process to remove spurious modes. The modified DMD algorithm thus developed was applied to the high Reynolds number, separation dominated flow past the idealized ground vehicle. The effectiveness of the modified algorithm was tested by comparing future predictions of force and moment coefficients as predicted by the DMD-based ROM to the reference CFD simulation data, and found to offer significant improvement.

A novel stationary phase for affinity separations is presented. This material is based on sintered borosilicate glass readily available as semi-finished filter plates with defined porosity and surface area. The material shows fast binding kinetics and excellent long-term stability under real application conditions due to lacking macropores and high mechanical rigidity. The glass surface can be easily modified with standard organosilane chemistry to immobilize selective binders or other molecules used for biointeraction. In this paper, the manufacturing of the columns and their respective column holders by 3D printing is shown in detail. The model system protein A/IgG was chosen as an example to examine the properties of such monolithic columns under realistic application conditions. Several specifications, such as (dynamic) IgG capacity, pressure stability, long-term performance, productivity, non-specific binding, and peak shape, are presented. It could be shown that due to the very high separation speed, 250 mg antibody per hour and column can be collected, which surpasses the productivity of most standard columns of the same size. The total IgG capacity of the shown columns is around 4 mg (5.5 mg/mL), which is sufficient for most tasks in research laboratories. The cycle time of an IgG separation can be less than 1 minute. Due to the glass material's excellent pressure resistance, these columns are compatible with standard HPLC systems. This is usually not the case with standard affinity columns, limited to manual use or application in low-pressure systems. The use of a standard HPLC system also improves the ability for automation, which enables the purification of hundreds of cell supernatants in one day. The sharp peak shape of the elution leads to an enrichment effect, which might increase the concentration of IgG by a factor of 3. The final concentration of IgG can be around 7.5 mg/mL without the need for an additional nanofiltration step. The purity of the IgG was > 95% in one step and nearly 99% with a second polishing run.

Posttraumatic stress disorder (PTSD) and/or specific PTSD symptoms may evoke disordered eating and unhealthy lifestyles, resulting in adverse cardiometabolic events (e.g., hypertension and obesity) in certain groups, which may implicate the treatment of this complex condition. The diagnostic criteria of PTSD have lately expanded beyond the three common symptoms (intrusion, avoidance, and hyperarousal). Simultaneously, four-, five-, and six-dimensional structures of the Impact of Event Scale-Revised (IES-R), a popular PTSD measure, seem to be more robust than the original three-dimension structure. Within the context of COVID-19, this instrumental study used a convenience sample of 58 dental healthcare workers (HCWs) from Russia (mean age = 44.1±12.2 years, 82.8% females) to examine the criterion and predictive validity of two IES-R structures: the IES-R3 and the IES-R6 (with the added symptoms of numbing, sleep disturbance, and irritability). The subscales of the two IES-R structures expressed good internal consistency, strong correlations with the PTSD Symptom Scale (PSS), hypertension diagnosis, and high body mass index (BMI). In receiver-operating characteristic (ROC) curve analysis, all IES-R models perfectly predicted the PSS (all area under the curve (AUC) >0.9, p values <0.001). The IES-R, both hyperarousal subscales, and the IES-R3 intrusion subscale significantly predicted high BMI. Both avoidance subscales and the IES-R3 intrusion subscale, not the IES-R, significantly predicted hypertension. In conclusion, both IES-R structures can reliably measure PTSD symptoms. The IES-R, hyperarousal, and intrusion may be credible criterion variables for predicting high BMI within PTSD while the intrusion and avoidance subscales may reflect the cardiovascular consequences associated with PTSD more reliably than the IES-R itself. The IES-R subscales may predict cardiometabolic adversities in PTSD, signifying a need for proper assessment of lifestyle and the application of dietary and exercise interventions in order to lower physical morbidity in PTSD. Replicating the study in larger samples, which comprise different physical and mental conditions from heterogenous cultural contexts is pivotal to validate the results (e.g., in specific groups such as those with confirmed traumatic exposure and comorbid mood dysfunction).

Neuroblastoma (NB) is a solid tumor occurring in infancy and childhood, whose high-risk form has currently a survival rate &lt; 50 %, despite aggressive treatments. Additionally, drugs-induced secondary tumorigenesis and the emergency of drug resistance worsen the already worrying scenario, calling for an urgent development of new extra-genomic treatments. Quaternary phosphonium salts (QPSs) possess both antimicrobial and anticancer effects. Triphenyl phosphonium salts (TPPs) are mitochondria-targeting compounds, exerting anticancer effects, impairing mitochondria functions and damaging DNA, at the same time. TPP-based bola-amphiphiles, previously proven to self-assemble nanoparticles (NPs) in water and successfully assayed as possible antibacterials, were never tested as suitable antitumor agents. Here, aiming at the development of new antitumor devices to counteract resistant forms of NB, the anticancer effects of a TPP-based amphiphile molecule have been investigated for the first time. To this end, we considered the water-soluble sterically hindered quaternary phosphonium salt (BPPB) encompassing two triphenyl phosphonium groups linked by a C12 alkyl chain, thus embodying both the characteristics of mitochondria-targeting compounds and those of bola-amphiphiles. The anticancer effects of BPPB were assessed against HTLA-230 human stage-IV NB cells and their counterpart resistant to etoposide (ETO), doxorubicin (DOX) and to many other therapeutics (HTLA-ER). Determined IC50 values were very low on both cell populations, already after 24 hours of treatment, when cells viability did not significantly differ from that observed for the longest exposure timing. Moreover, to investigate a putative future inclusion of BPPB in a chemotherapeutic cocktail for NB, its cytotoxic effects were assessed against mammalian cell lines. These included monkey kidney cells (Cos-7), human hepatic cells (HepG2), a lung-derived fibroblast cell line (MRC-5) and red blood cells. From appreciable to very high selectivity indices have been determined after 24 hours treatments, an exposure time after which both NB cell populations tested appeared already fully exterminated.

We report a case of colloid carcinoma (CC) arising from an intestinal-type intraductal papillary mucinous neoplasm with high-grade dysplasia (IPMNHGD) of the pancreas, diagnosed with serial pancreatic juice aspiration cytological examination (SPACE). A rapidly growing intraductal papillary mucinous neoplasm (IPMN) in a 71-year-old Japanese man accelerated his hospitalization in our institute. Clinically, a large, ruptured pancreatic cyst was suspected. Cytologically, several mucin-positive signet-ring cells were scattered in the inflammatory, necrotic, or mucinous background. Signet-ring cells in cell block specimens were immunoreactive for MUC2, MUC5AC, maspin, S100P, and claudin-18. The final cytologic diagnosis was CC arising in an intestinal-type IPMNHGD with intraperitoneal penetration. The patient died two months postoperatively. The cytologic diagnosis was achieved through SPACE, and the presence of signet-ring cells was characteristic. Anti-claudin-18.2-specific monoclonal antibody therapy will likely be used to treat patients with IPMNHGD in the future. To our knowledge, this is the first report in English on mucin-positive signet-ring cells of CC arising in an intestinal-type IPMNHGD evaluated by SPACE cytology.

The morphology of virgin reactor powder (RP) of high-density polyethylene HDPE with MW = 160,000 g/mol was investigated with the help of DSC, SEM, SAXS and WAXS methods. The morphological SEM analysis showed, that the main morphological units of RP are macro- and micro-shish kebab structures with significantly different geometric dimensions, as well as individual lamellae of folded chain crystals. Quantitative analysis of an asymmetric SAXS reflection made it possible to reveal the presence of several periodic morphoses in the RP with long periods from 20 nm to 60 nm and to correlate them with the observed powder morphology. According to the DSC crystallinity data, the thickness of the lamellae in each long period was estimated. Their surface energy was calculated in the framework of the Gibbs-Thompson theory. The presence of regular and irregular folds on the surface of the different shish-kebab lamellae is discussed. The percentage of identified morphoses in the RP was calculated. It has been suggested that the specific structure of HDPE RP is due to the peculiarity of polymer crystallization during suspension synthesis in a quasi-stationary regime, in which local overheating and inhomogeneous distribution of shear stresses in a chemical reactor are possible.

The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n=11) and patients with PDAC (n=24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using Ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia.

Several studies have shown that physical activity (PA) is related to physical and mental health. Yet, there are few studies on the frequency of PA as it relates to health and a healthy lifestyle. The purpose of this study was to investigate the relationship between the frequency of practicing different types of physical activities (dependent variables), living a healthy lifestyle (BMI, smoking and alcohol consumption), physical health (sum of all doctor visits except psychiatrists) and mental health (a sum of visits to psychiatrists) at different ages (independent variables). We fo-cused on three types of PA: (1) medium to high-intensity aerobic exercises; (2) low to medium intensity relaxing and stretching exercises, (3) outdoor leisure PA. 9,617 participants (ages: 19 -81) were included in the study (with health registries over a period of 10 years prior to a cross-sectional survey). Descriptive statistics and multinomial logistic regression on frequencies of three types of PA and factors related to health and healthy lifestyles, as well as age and sex, were performed in this study. The results indicate that a higher frequency of practicing PA had a higher probability of association with the following factors: lower BMI, less or non-smoking behavior (types 1 & 3); higher education (types 1 & 2); higher age (types 2 & 3) and better physical health (type 1). Occasional (practicing sometimes) PA, type 2, was positively associated with poorer mental health (higher number of psychiatrist visits). Women were more likely to practice PA type 2, and men – PA types 3 & 1. Conclusion: In general, a higher frequency of PA is related with better health and healthy life styles; with the exception of PA type 2 that is related to poorer mental health.

The goods and services produced by forest vegetation ecosystem are the driving force for the rapid, high-quality and sustainable development of human society. In history, with the increase of population and economic development, there is an increasing demand for the quantity and variety of forest vegetation ecosystem products and services in a country or a region. To meet the demands, most of the original forest has become farmland, plantation and grass and crops land. As a result, the plant water relationship changed from equilibrium to non-equilibrium, which easily led to soil drought, soil degradation and vegetation decline in dry years or waste of soil water in rainy years in most of water-limited regions. In order to solve the question and realize the sustainable utilization of soil water resources and the high-quality sustainable development of forest, it is necessary to apply the limit theory of plant utilization of soil water resources and the vegetation carrying capacity theory in the critical period of plant-water relationship regulation to adjust the relationship between plant growth and soil moisture to obtain the maximum yield and benefit and realize high-quality and sustainable development.

Background: Co-treatment of the fetal estrogen estetrol (E4) with androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) may further inhibit endocrine PCa tumor stimulators including testosterone (T), prostate-specific antigen (PSA), follicle-stimulating hormone (FSH), and insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study in advanced PCa patients requiring ADT (the PCombi study) was conducted to assess the effect of E4 co-treatment with LHRH agonist ADT on total T, free T, PSA, FSH, and IGF-1. Patients starting ADT were randomized 2:1 to 40 mg E4 (n=41) or placebo (n=21) for 24 weeks. Analyses were performed on the per-protocol population (PP), using the Wilcoxon-rank sum and the Kruskal-Wallis test. Results: The PP population consisted of 57 patients (37 ADT+E4; 20 ADT+placebo). All individual data of the four endocrine tumor stimulators are presented in figures in the paper and in supplementary tables, showing that E4 co-treatment almost completely suppressed FSH levels in all patients, on average by 98% versus 37% in the placebo group (p

While paresthesia-based spinal cord stimulation (SCS) has been proven effective to treat chronic neuropathic pain, initial benefits may lead to the development of “Failed SCS Syndrome’ (FSCSS) defined as decrease over time related to Loss of Efficacy (LoE) with or without Loss of Coverage (LoC). Development of technologies associating new paresthesia-free stimulation waveforms and implanted pulse generator adapters provide opportunities to manage patients with LoE. The main goal of our study was to investigate salvage procedures, through neu-rostimulation adapters, in patients already implanted with SCS and experienced LoE. We retro-spectively analyzed a cohort of patients who were offered new SCS programs/waveforms through an implanted adapter between 2018 and 2021. Patients were evaluated before, and at 1, 3, 6 and 12-month follow-up. Outcomes included pain intensity rating with Visual Analog Scale (VAS), pain/coverage mappings and stimulation preferences. Last follow-up evaluations (N=27) showed significant improvement in VAS (p = 0.0001), ODI (p = 0.021) and Quality of Life (p=0.023). In the 11/27 patients with LoC, SCS efficacy on pain intensity (36.89%) was accompa-nied by paresthesia coverage recovery (55.57%) and pain surface decrease (47.01%). At 12-month follow-up, 81.3% preferred to keep tonic stimulation in their waveform portfolio. SCS conver-sion using adapters appears promising as a salvage solution, with an emphasis on paresthesia recapturing enabled by spatial retargeting. In light of these results, adapters could be integrated to SCS rescue algorithms or should be considered in SCS rescue.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

Multi-junction solar cells comprised of stacked III-V semiconductor junctions represent the highest-efficiency photovoltaic technology, with recent demonstrations exceeding 47% efficiency . Optimizing the design and thickness of each junction is critical for maximizing performance . This work utilizes Silvaco TCAD tools to systematically optimize a 5-junction cell based on AlInP, AlGaInP, AlGaInAs, GaInP, GaAs, InGaAs, and Ge similar to recent record cells . The junction thicknesses are varied using a predictive profiler to sample the parameter space . For each combination, the spectral absorption and I-V characteristics are simulated to determine the efficiency . Statistical analysis identifies the optimal thickness set that maximizes performance to 26% under 1 sun illumination .

During the conceptual and preliminary design stage of a ship, designers need to ensure that the selected principal dimensions and parameters are good enough to deliver a stable ship (statically and dynamically) besides deadweight and speed. To support this, the initial intact stability of the proposed ship is required to be calculated, and in doing so, the lightship weight and its detailed breakdown are necessary to be known. After hull steel weight, machinery weight, mainly, marine propulsion and power generation machinery, play a vital role in the lightship weight estimate of a ship due to its robustness. The correct estimation of respective weights improves the accuracy of calculating a ship's initial stability typically to be designed and built. Hence, it would be advantageous for the designer to convince the ship owner. A total of 3006 marine propulsion (main marine diesel) engines and 348 power generation (auxiliary marine diesel) engines/generators of various power output (generators output for auxiliary engines), engine RPM and cylinder number of different engine makers are collected. These are analyzed and presented in both tabular and graphical forms to demonstrate the possible relationship between marine propulsion engine weight and power generation engine weight, and their respective power output, RPM, cylinder number, power-RPM ratio and power-RPM ratio per cylinder.In this article, the authors have attempted to investigate the behavior of marine propulsion engine weight and power generation engine/generator weight regarding engine power output, generator power output, engine RPM and cylinder number (independent variables). Further attempts have been made to identify those independent variables that influence the weight of the marine propulsion engine and power generation engine/generator (dependent variables), and their interrelationships. A mathematical model has thus been developed and proposed, as a guiding tool, for the designer to estimate the weight of main and auxiliary engines more accurately during the conceptual and preliminary design stage.

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

This literature review investigates the role of plumage in the hunting tactics of Velociraptor, integrating anatomical analysis and biomechanical modeling. Velociraptor, a swift and agile theropod from the Late Cretaceous, exhibited advanced intelligence and sensory capabilities that contributed to its effective predatory strategies. Recent discoveries have confirmed that Velociraptor was covered in feathers, with quill knobs indicating well-developed plumage. This review explores the potential functions of feathers beyond flight, focusing on their impact on hunting behavior. Evidence suggests that Velociraptor’s plumage likely facilitated camouflage and enhanced aerodynamic control, improving its stealth and maneuverability during high-speed chases. Additionally, feathers might have contributed to stability during incline running, further supporting its adaptability in diverse environments. Velociraptor’s hunting strategies, characterized by agility and precision, were complemented by its feathered anatomy, which may have also played a role in pack hunting and social interactions. Overall, the integration of plumage with Velociraptor’s anatomical features and behavioral adaptations underscores its efficiency as a predator, demonstrating how feathers may have been a critical factor in its successful hunting tactics.

The trafficking of illegal drugs by criminal networks at borders, harbors, or airports is an increasing issue in public health as these routes ensure the main supply of illegal drugs. The prevention of drug smuggling, including the installation of scanners and other analytical devices to detect ultra-small traces of drugs within a reasonable time frame, remains a challenge. The presented immunosensor is based on a monolithic affinity column with a large excess of immobilized hapten, which traps fluorescently labeled antibodies as long as the analyte cocaine is absent. In the presence of the drug, some binding sites of the antibody will be blocked, which leads to an immediate breakthrough of the labeled protein, detectable by highly sensitive laser-induced fluorescence with the help of a Peltier-cooled complementary metal-oxide-semiconductor (CMOS) camera. Liquid handling is performed with high-precision syringe pumps and microfluidic chip-based mixing devices and flow cells. The biosensor achieved limits of detection of 23 pM (7 ppt) of cocaine with a response time of 90 seconds and a total assay time below 3 minutes. With surface wipe sampling, the biosensor was able to detect 300 pg of cocaine. This immunosensor belongs to the most sensitive and fastest detectors for cocaine and offers near-continuous analyte measurement.

The war to technology and economic power have been the driver for industrialization in most developed countries. The first industrial revolution (industry 1.0) earned millions for textile mill owners while the second industrial revolution (industry 2.0) opened the way for tycoons and captains of industry like John D. Rockefeller, J.P. Morgan and Henry Ford. The third industrial revolution (industry 3.0) engendered technology giants like Apple and Microsoft, and made magnates of men like Steve Jobs and Bill Gates. Now, the race for the fourth industrial revolution (industry 4.0) is on and there is no option, every country whether developed or developing must participate. Many countries have positively responded to industry 4.0 by developing strategic initiatives to strengthen industry 4.0 implementation. Unlocking the country’s potential to industry 4.0 has been of interest to researchers in the recent past. However, the extent to which industry 4.0 initiatives being launched globally has never been revealed. Therefore, the present study aimed at exploring industry 4.0 initiatives through comprehensive electronic survey of literature to estimate the extend of its launching in different regions. Inferences were drawn from industry 4.0 initiatives in developed nations to be used as the recommendations for East Africa Community. Results of the survey revealed that 117 industry 4.0 initiatives have been launched in 56 countries worldwide consisting of five regions. The country’s percent of industry 4.0 initiatives as per region were: Latin America and the Caribbean (15%), North America (40%), Europe (53%), Asia and Oceania (25%), Middle East and Africa (11%). While the worldwide percent was estimated as 25%. This revealed that the big gap is existing between countries towards the race for industry 4.0.

We present an overview over eight brightly luminescent Cu(I) dimers of the type Cu2X2(PN)3 with X = Cl, Br, I and P^N = 2-diphenylphosphino-pyridine (Ph2Ppy), 2-diphenylphosphino-pyrimidine (Ph2Ppym), 1-diphenylphosphino-isoquinoline (Ph2Piqn) including three new crystal structures (Cu2Br2(Ph2Ppy)3, 1-Br, Cu2I2(Ph2Ppym)3, 2-I, and Cu2I2(Ph2Piqn)3, 3-I). However, we mainly focus on their photo-luminescence properties. All compounds exhibit combined thermally activated delayed fluorescence (TADF) and phosphorescence at ambient temperature. Emission color, decay time, and quantum yield varies over large ranges. For deeper characterization, we select Cu2I2(Ph2Ppy)3, 1-I, showing a quantum yield of 81 %. DFT and SOC-TDDFT calculations provide insight into the electronic structures of the singlet S1 and triplet T1 states. Both stem from metal+iodide-to-ligand charge transfer transitions. Evaluation of the emission decay dynamics, measured from 1.2 ≤ T ≤ 300 K, gives ∆E(S1-T1) = 380 cm-1 (47 meV), a transition rate of k(S1→S0) = 2.25×106 s-1 (445 ns), T1 zero-field splittings, transition rates from the triplet substates, and spin-lattice relaxation times. We also discuss the interplay of S1-TADF and T1-phosphorescence. The combined emission paths shorten the overall decay time. For OLED applications, utilization of both singlet and triplet harvesting can be highly favorable for improvement of the device performance.

This paper introduces an innovative theoretical framework for quantum-inspired data embeddings, grounded in foundational concepts of quantum mechanics such as superposition and entanglement. This approach aims to advance semi-supervised learning in contexts characterized by limited labeled data by enabling more intricate and expressive embeddings that capture the underlying structure of the data effectively. Grounded in foundational quantum mechanics concepts such as superposition and entanglement, this approach redefines data representation by enabling more intricate and expressive embeddings. Emulating quantum superposition encodes each data point as a probabilistic amalgamation of multiple feature states, facilitating a richer, multidimensional representation of underlying structures and patterns. Additionally, quantum-inspired entanglement mechanisms are harnessed to model intricate dependencies between labeled and unlabeled data, promoting enhanced knowledge transfer and structural inference within the learning paradigm. In contrast to conventional quantum machine learning methodologies that often rely on quantum hardware, this framework is fully realizable within classical computational architectures, thus bypassing the practical limitations of quantum hardware. The versatility of this model is illustrated through its application to critical domains such as medical diagnosis, resource-constrained natural language processing, and financial forecasting—areas where data scarcity impedes the efficacy of traditional models. Experimental evaluations reveal that quantum-inspired embeddings substantially outperform standard approaches, enhancing model resilience and generalization in high-dimensional, low-sample scenarios. This research marks a significant stride in integrating quantum theoretical principles with classical machine learning, broadening the scope of data representation and semi-supervised learning while circumventing the technological barriers of quantum computing infrastructure.

Two-Dimensional Nuclear Magnetic Resonance (2D NMR) spectroscopy has become a cornerstone in pharmaceutical research, offering enhanced structural elucidation capabilities for complex molecules. This technique overcomes the limitations of one-dimensional (1D) NMR by providing detailed insights into molecular interactions through the use of advanced spectroscopic methods like COSY, HSQC, and HMBC. In pharmaceutical applications, 2D NMR plays a crucial role in drug characterization, quality control, formulation development, and the structural analysis of natural products. Recent technological advancements such as high-field spectrometers and cryogenic probes have further improved the sensitivity and resolution of 2D NMR, making it indispensable for ensuring drug quality and intellectual property protection. This article delves into the principles and applications of 2D NMR in the pharmaceutical industry, highlighting its critical contributions to drug discovery, development, and quality assurance. Additionally, it addresses the future prospects of 2D NMR in areas like metabolomics, structural biology, and the development of new analytical tools. Despite its numerous advantages, 2D NMR presents challenges such as high operational costs, complexity in data analysis, and sensitivity issues when dealing with low-concentration samples. The article concludes by discussing the ongoing advancements in 2D NMR technology and its evolving role in pharmaceutical innovation.

We work within a Winterberg framework where space, i.e., the vacuum, consists of a two component superfluid/super-solid made up of a vast assembly (sea) of positive and negative mass Planck particles, called planckions. These material particles interact indirectly, and have very strong restoring forces keeping them a finite distance apart from each other within their respective species. Because of their mass compensating effect, the vacuum appears massless, charge-less, without pressure, net energy density or entropy. In addition, we consider two variable models, where, , is Newton’s constant, and, , increases with an increase in cosmological time. We argue that there are at least two competing models for the quantum vacuum within such a framework. The first follows a strict extension of Winterberg’s model. This leads to nonsensible results, if increases, going back in cosmological time, as the length scale inherent in such a model will not scale properly. The second model introduces a different length scale, which does scale properly, but keeps the mass of the Planck particle as, the Planck mass. Moreover we establish a connection between ordinary matter, dark matter, and dark energy, where all three mass densities within the Friedman equation must be interpreted as residual vacuum energies, which only surface, once aggregate matter has formed, at relatively low temperatures. The symmetry of the vacuum will be shown to be broken, because of the different scaling laws, beginning with the formation of elementary particles. Much like waves on an ocean where positive and negative planckion mass densities effectively cancel each other out and form a zero vacuum energy density/ zero vacuum pressure surface, these positive mass densities are very small perturbations (anomalies) about the mean. This greatly alleviates, i.e., minimizes the cosmological constant problem, a long standing problem associated with the vacuum.

The Hyper-Torus Universe Model (HTUM) proposes a novel framework to unify quantum mechanics, cosmology, and consciousness. This paper introduces HTUM's core concept: a higher-dimensional hyper-torus encompassing all possible states of existence. HTUM suggests that the universe functions as a quantum system where all outcomes are inherently connected, with consciousness playing a significant role in actualizing reality. The model introduces several key innovations, including the universe's 4-dimensional toroidal structure (4DTS), providing a new geometric interpretation of spacetime. HTUM presents dark matter and dark energy as nonlinear probabilistic phenomena within this toroidal framework, offering a unique perspective on their nature and interactions. The model proposes a mechanism for wave function collapse through universal self-observation, bridging quantum mechanics and gravity. It introduces a Topological Vacuum Energy Modulator (TVEM) function, offering a potential resolution to the cosmological constant problem. Furthermore, HTUM integrates consciousness as a fundamental aspect of the universe, influencing quantum state actualization and potentially resolving the hard problem of consciousness. The model explores the implications of a timeless singularity and the emergence of time as a product of causal relationships within the toroidal structure. This framework addresses critical challenges in modern physics, including the nature of quantum entanglement, the origin and fate of the universe, and the relationship between mind and matter. The paper discusses the mathematical formulation of HTUM, its implications for quantum mechanics and cosmology, and its potential to bridge the gap between science and philosophy. We present detailed predictions for the cosmic microwave background (CMB) power spectrum, gravitational wave signatures, and large-scale structure formation, demonstrating how HTUM differs from the standard ΛCDM model. Our analysis reveals distinctive oscillatory patterns in the relative difference between HTUM and ΛCDM predictions, with deviations reaching up to ±20% at certain scales. The paper also explores the unification of fundamental forces within the HTUM framework, proposing novel approaches to particle physics and quantum field theory. It introduces the concept of unified mathematical operations, suggesting a more holistic approach to mathematical thinking that aligns with the model's interconnected view of the universe. Additional testable predictions and proposed experimental approaches are discussed, including advanced space-based tests and laboratory experiments probing quantum gravity effects. These specific, quantifiable predictions offer multiple avenues for empirical validation, highlighting HTUM's potential to be distinguished from ΛCDM and other alternative cosmological models. HTUM represents a significant new perspective in our understanding of the universe, inviting further research and exploration into the nature of reality, consciousness, and the fundamental structure of the cosmos. By providing a comprehensive framework that unifies various aspects of physics, cosmology, and consciousness studies, HTUM offers a promising path toward a more complete understanding of our universe.

Backward electromagnetic waves are extraordinary waves with contra-directed phase velocity and energy flux. Unusual properties of the coherent nonlinear optical coupling of the phase-matched ordinary and backward electromagnetic waves with contra-directed energy fluxes are described which enable greatly-enhanced frequency and propagation direction conversion, parametrical amplification, as well as control of shape of the light pulses. Extraordinary transient processes that emerge in such metamaterials in pulsed regimes are described. The results of the numerical simulation of particular plasmonic metamaterials with hyperbolic dispersion are presented, which prove the possibility to match phases of such coupled guided ordinary and backward electromagnetic waves. Particular properties of the outlined processes in the proposed metamaterial are demonstrated through numerical simulations. Potential applications include ultra-miniature amplifiers, frequency changing reflectors, modulators, pulse shapers, and remotely actuated sensors.