To improve accessibility, this article describes a static, four-legged, walker that can be constructed from materials and fasteners commonly available from hardware stores coupled by open-source 3-D printed joints. The designs are described in detail, shared under an open-source license, and fabricated with a low-cost open-source desktop 3-D printer and hand tools. The resulting device is loaded to failure to determine the maximum load that the design can safely support in both vertical and horizontal failure modes. The experimental results showed the average vertical failure load capacity was 3680±694.3N, equivalent to 375.3±70.8kg of applied weight with the fractured location at the wood dowel handlebars. The average horizontal load capacity was 315.6±49.4N, equivalent to 32.2±5.1kg. The maximum weight capacity of a user of 187.1±29.3kg was obtained, which indicates the open-source walker design can withstand the weight requirements of all genders with a 95% confidence interval that includes a safety factor of 1.8 when considering the lowest deviation weight capacity. The design has a cost at the bottom of the range of commercial walkers and reduces the mass compared to a commercial walker by 0.5kg (19% reduction). It can be concluded that this open-source walker design can aid accessibility in low-resource settings.

Low-lying coastal communities are often threatened by compound flooding (CF), which can be determined through the joint occurrence of storm surges, rainfall and river discharge either successively or in close succession. The trivariate distribution can demonstrate the risk of the compound phenomenon more realistically rather than considering each contributing factor independently or in a pairwise dependency. Recently vine copula has been recognized as the highly flexible approach to constructing a higher dimensional joint density framework. In such construction, parametric class copula with parametric univariate marginal distributions is often involved. Such incorporation can lack flexibility due to parametric functions with prior distribution assumptions about their univariate marginal and/or copula joint density. This study introduces the vine copula approach in a nonparametric setting by introducing Bernstein and Beta kernel copula density in establishing trivariate flood dependence. The proposed model is applied to 46 years of flood characteristics collected on the west coast of Canada. The univariate flood marginal distribution is modelled using nonparametric kernel density estimation (KDE). The 2-D Bernstein estimator and Beta kernel copulas estimator are tested independently in capturing pairwise dependencies to establish D-vine structure in a stage-wise nesting approach in three alternative ways, each by permutating the location of the conditioning variable. The best-fitted vine structure is selected using goodness-of-fit (GOF) test statistics. The performance of the nonparametric vine approach is also compared with the vine constructed in the parametric and semiparametric fitting procedure. Investigation reveals that the D-vine constructed using Bernstein copula with normal KDE marginals nonparametrically performed well in capturing dependence of the compound events. Finally, the derived nonparametric model is used in the estimation of trivariate OR- and AND-joint return periods, further employed in estimating failure probability (FP) statistics. The trivariate return periods for the AND-joint case are higher than for the OR-joint case for the same flood combination. Also, the trivariate flood hazard results in a high-value FP than bivariate and univariate events. Ignoring the trivariate dependence could result in the underestimation of FP

PHLNs (polymeric lipid hybrid nanoparticles) are core–shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) & glyceryl tripalmitate prepared using solvent injection & homogenization method for glioblastoma treatment option. The MTX loaded PLHNPs optimized by Box–Behnken design to minimize particle size, higher entrapment efficacy, and maximize MTX concentration in the brain at 4h. The particle size, entrapment efficacy, concentration of drug in brain at 4h, zeta potential and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51-233.37nm, 70.56-86.34%, 6.38-12.38 μg/mL, 25.78-36.31mV & 1.02-5.32. in-vitro drug release studies, cellular internalization of optimized formulation against U-87 MG shows good anticancer effects.

Barriers to inventing electronic devices involve challenges of iterating electronic designs due to long lead times for professional circuit board milling or high-costs of commercial milling machines. To overcome these barriers this study provides open source (OS) designs for a low-cost circuit milling machine. First, design modifications for mechanical and electrical sub-systems of the OS D3D Robotics prototyping system are provided. Next, Copper Carve, an OS custom graphical user interface, is developed to enable circuit board milling by implementing backlash and substrate distortion compensation. The performance of the OS D3D circuit mill is then quantified and validated for: positional accuracy, cut quality, feature accuracy and distortion compensation. Finally, the return on investment is calculated for inventors using it. The results show by properly compensating for motion inaccuracies with Copper Carve, the machine achieves a motion resolution of 10 microns, which is more than adequate for most circuit designs. The mill is at least five times less expensive than all commercial alternatives and the material costs of the D3D mill are repaid from fabricating 20-43 boards. The results show that the OS circuit mill is of high-enough quality to enable rapid invention and distributed manufacturing of complex products containing custom electronics.

A useful and increasingly common additive manufacturing (AM) process is the selective laser melting (SLM) or direct metal laser sintering (DMLS) process. SLM/DMLS can produce full-density metal parts from difficult materials, but it tends to suffer from severe residual stresses introduced during processing. This limits the usefulness and applicability of the process, particularly in the fabrication of parts with delicate overhanging and protruding features. The purpose of this study was to examine the current insight and progress made toward understanding and eliminating the problem in overhanging and protruding structures. To accomplish this, a survey of literature was undertaken, focusing on process modeling (general, heat transfer, stress and distortion, and material models), direct process control (input and environmental control, hardware-in-the-loop monitoring, parameter optimization, and post-processing), experiment development (methods for evaluation, optical and mechanical process monitoring, imaging, and design-of-experiments), support structure optimization, and overhang feature design; approximately 140 published works were examined. The major findings of this study were that a small minority of the literature on SLM/DMLS deals explicitly with the overhanging stress problem, but some fundamental work has been done on the problem. Implications, needs, and potential future research directions are discussed in-depth in light of the present review.

Hydraulic fracturing has enabled production from unconventional reservoirs in the U.S., but production rates often decline sharply, limiting recovery factors to under 10%. This study optimizes the CO2 huff-n-puff process for multistage-fractured horizontal wells in Wolfcamp A formation in the Delaware Basin. The potential for enhanced oil recovery and CO2 sequestration simultaneously was addressed using a coupled geomechanics-reservoir simulation. Geomechanical properties were derived from a 1D mechanical earth model and integrated into reservoir simulation to replicate hydraulic fracture geometries. The fracture model was validated using a robust production history matching. Fluid phase behavior analysis refined the equation of state, and 1D slim tube simulations determined a minimum miscibility pressure of 4300 psi for CO2 injection. After the primary production phase, various CO2 injection rates were tested from 1 to 25 MMSCFD/well, resulting in incremental oil recovery ranging from 6.3% to 69.3%. Different injection, soaking, and production cycles were analyzed to determine the ideal operating condition. The optimal scenario improved cumulative oil recovery by 68.8% while keeping the highest CO2 storage efficiency. The simulation approach proposed by this study provides a systematic workflow for evaluating and optimizing CO2 huff-n-puff in hydraulically fractured wells, enhancing the recovery factor of unconventional reservoirs.

Materials engineering based on metal oxides for manipulating the solar spectrum and producing solar energy have been under intense investigation over the last years. In this work, we present NiO thin films double-doped with niobium (Nb) and nitrogen (N) as cation and anion dopants (NiO:(Nb,N)) to be used as p-type layers in all oxide transparent solar cells. The films were grown by sputtering a composite Ni-Nb target on room-temperature substrates in plasma containing 50% Ar, 25% O2 and 25% N2 gases. The existence of Nb and N dopants in the NiO structure was confirmed by the Energy Dispersive X-Ray and X-Ray Photoelectron Spectroscopy techniques. The nominally undoped NiO film, which was deposited by sputtering a Ni target and used as the reference film, was oxygen-rich, single-phase cubic NiO, having a visible transmittance of less than 20%. Upon double doping with Nb and N the visible transmittance of NiO:(Nb,N) film increased to 60%, which was further improved after thermal treatment to around 85%. The respective values of the direct band gap in the undoped and double-doped films were 3.28 eV and 3.73 eV just after deposition and 3.67 eV and 3.76 eV after thermal treatment. The changes in the properties of the films such as structural disorder, direct and indirect energy band gaps, Urbach tail states and resistivity were correlated with the incorporation of Nb and N in their structure. The thermally treated NiO:(Nb,N) film was used to form a diode with a spin-coated two-layer, mesoporous on top of a compact, TiO2 film. The NiO:(Nb,N)/TiO2 heterojunction exhibited visible transparency of around 80%, showed rectifying characteristics and the diode’s parameters were deduced using the I-V method. The diode revealed photovoltaic behavior upon illumination with UV light exhibiting a short circuit current density of 0.2 mA/cm2 and open-circuit voltage of 500 mV. Improvements of the output characteristics of the NiO:(Nb,N)/TiO2 UV-photovoltaic by proper engineering of the individual layers and device processing procedures are addressed. Transparent NiO:(Nb,N) films can be potential candidates in all-oxide ultraviolet photovoltaics for tandem solar cells, smart windows and other optoelectronic devices.

The predatory mirids Macrolophus pygmaeus Ramber and Nesidiocoris tenuis Reuter (Heteroptera: Miridae) are used for the biological control of Tuta absoluta Meyrick (Lep.: Gelechiidae) and other pests in tomato greenhouses. The functional response of 1 (young) and 10 (old) days old adult females and males of M. pygmaeus and N. tenuis on eggs of T. absoluta, was determined on tomato at two temperatures (20° and 25°C) and LD 16:8 and found to be Type II. M. pygmaeus females exhibited higher predation efficiency, than males at both tested temperatures. Young M. pygmaeus females had a higher efficiency than old ones, whereas males had a low efficiency irrespective of age. The predation efficiency of N. tenuis was high (but lower than M. pygmaeus) in both young females and males, although old females had a higher efficiency than the respective males. Our results show that the two predatory species have different functional response characteristics to their prey depending mainly on sex and age which may affect their role as biological control agents.

In addition to nucleic acids, various viral proteins are involved in the assembly of virion. If it is possible to create a biologically active agent that leads to the degradation of one of the key proteins for virus assembly and/or destroys the viral factory, then this agent will effectively cope with virus replication. One of these key proteins for the SARS-CoV-2 virus is the nucleocapsid protein (N-protein). As such a bioactive agent, we offer a modular nanotransporter (MNT) developed by us, which, in addition to an antibody mimetic to the N-protein, contains an amino acid sequence for the attraction of the Keap1 E3 ubiquitin ligase. This should lead to the subsequent degradation of the N-protein. We have shown that functional properties of modules within the MNT permit its internalization into target cells, endosome escape into the cytosol, and binding to the N-protein. Using flow cytometry and Western blot, it was demonstrated that significant degradation of N-protein is observed when A549 and A431 cells transformed with N-protein are incubated with the developed MNTs. The proposed MNTs open up a new approach for the treatment of viral diseases.

The excessive use of synthetic insecticides in modern agriculture has led to the contamination of the environment and the development of insect resistance. In this study, we evaluated the potential of tangerine (Citrus reticulata L.) peel essential oil (EO) as a natural insecticide against greenhouse whitefly (Trialeurodes vaporariorum W. (Homoptera: Aleyrodidae)), a common pest in greenhouse production. Petroleum ether (PET) and n-hexane (HEX) were used as solvents to extract essential oil (EO) from tangerine peels. The yield of EO was 1.59 % and 2.00 % (m/m) for PET and HEX, respectively. The insecticidal activity of EO was evaluated by measuring the mortality rate (MR) of greenhouse whiteflies at different time intervals. The results showed that PET and HEX extracts of tangerine EO effectively controlled the greenhouse whitefly. With both solvents, it was observed that with doses of 12.5% (v/v), similar results were achieved as with the positive control (corresponding to the commercial insecticide imidacloprid). Additionally, the FTIR analysis found that the EO contained d-limonene, which may be the source of its insecticidal properties. Therefore, tangerine peel essential oil is an excellent natural insecticide candidate for controlling greenhouse whiteflies effectively and sustainably.

Antisense oligonucleotide (ASO)-mediated exon skipping has become a valuable tool for investigating gene function and developing gene therapy. Machine learning-based computational methods such as eSkip-Finder have been developed to predict the efficacy of ASOs via exon skipping. However, these methods are computationally demanding, and the accuracy of predictions remains suboptimal. In this study, we propose a new approach to reduce computational burden and improve prediction performance by using feature selection within machine learning algorithms and ensemble learning techniques. We evaluated our approach using a dataset of experimentally validated exon skipping events, dividing it into training and testing sets. Our results demonstrate that using a 3-way voting approach with random forest, gradient boosting, and XGBoost can significantly reduce computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2’-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. Our findings suggest that our approach has the potential to enhance the accuracy and efficiency of predicting ASO efficacy via exon skipping. It could also facilitate the development of novel therapeutic strategies. This study could contribute to the ongoing efforts to improve ASO design and optimize gene therapy approaches.

Antisense oligonucleotide (ASO)-mediated exon skipping has emerged as a powerful tool for examining the function of genes and exons in basic research, as well as gene therapy. Computational methods, such as eSkip-Finder, have been developed to predict the efficacy of ASOs via exon skipping using machine learning. However, these methods can be computationally demanding and the prediction accuracy of the tool is not yet optimal. In this study, we propose an approach to reduce computational burden and improve prediction performance by utilizing feature selection within machine learning algorithms and employing ensemble learning techniques. The method was evaluated using a dataset of genes with experimentally validated exon skipping events. The dataset was divided into training and testing sets to assess the accuracy of the algorithm. Our results demonstrate that using a 3-way voting approach with random forest, gradient boosting, and XGBoost can significantly reduce computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2’-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. These findings suggest that this approach has the potential to enhance the efficiency and accuracy of predicting ASO efficacy via exon skipping, facilitating the development of novel therapeutic strategies.

The enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B; ARSB) was originally identified as a lysosomal enzyme which was deficient in Mucopolysaccharidosis VI (MPS VI; Maroteaux-Lamy Syndrome). Newly directed attention to the impact of ARSB in human pathobiology indicates a broader, more pervasive effect, encompassing roles as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling. By controlling the degradation of chondroitin 4-sulfate and dermatan sulfate by removal or failure to remove the 4-sulfate residue at the non-reducing end of the sulfated glycosaminoglycan chain, ARSB modifies the binding or release of critical molecules into the cell milieu. These molecules, such as galectin-3 and SHP-2, in turn, influence crucial cellular processes and events which determine cell fate. Identification of ARSB at the cell membrane and in the nucleus expands perception of the potential impact of decline in ARSB activity. Regulation of availability of sulfate from chondroitin 4-sulfate and dermatan sulfate may also affect sulfate assimilation and production of vital molecules, including glutathione and cysteine. Increased attention to ARSB in mammalian cells may help to integrate and deepen our understanding of diverse biological phenomenon and to approach human diseases with new insights.

The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for biocrimes in several cases. Here, the main steps of ricin research are reported with particular regards to its enzymatic activity, structure and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation amongst bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been of great utility to develop a number of immunotoxins specific for the elimination of unwanted cells, mainly cancer cells; some of these immunotoxins gave promising results also in clinical trials.

Daily vitamin D supplementation using higher than normal dosing (up to the upper limit, UL) and intermittent (once or twice per week) dosing were studied in patients with increased risk of vitamin D deficiency. Using a PubMed database an adequate search for published randomized control trials and other studies was done and results were analyzed. This review provides overview of use of 7000 IU daily, 30,000 IU per week or twice weekly and 50,000 IU weekly of vitamin D on rapid restore of 25(OH)D concentrations to at least 30 ng/mL in different groups of patients at high risk of vitamin D deficiency. The above mention dosing should be considered in adults with obesity or multi-diseased patients on requiring multi-treatment with the use of several drugs, including drugs affecting vitamin D metabolism. The simple schedule for 7000 IU/day, 30,000 IU/week or twice weekly or 50,000 IU/week, all for 6-8 weeks of use by patients representing the increased risk of vitamin D deficiency were provided for consideration. It appeared that higher daily doses or intermittent doses suggested above are effective, safe and responsive for patient’s preferences.

Plant hormones regulate the adaptive responses to various biotic and abiotic stress factors. Applied exogenously they trigger the natural plant defense mechanisms, a feature that could be implemented in strategies for supporting crop resilience. The potential of exogenous cytokinin-like acting compound (kinetin), the auxin analogue 1-naphtyl acetic acid (NAA), abscisic acid (ABA) and the ethylene-precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to mitigate dehydration was tested on Lactuca sativa (lettuce) grown on 12% polyethylene glycol (PEG). Priming with different blends containing these plant growth regulators applied in bioequivalent concentrations was evaluated through biometric measurements and biochemical analyses. The combined treatment with the four plant hormones exhibited the best dehydration protective effect. The antioxidative enzyme profiling of the PGR-primed individuals revealed increased SOD, catalase and peroxidase activity in the leaves. Immunodetection of higher levels of the rate-limiting enzyme for proline biosynthesis (delta-pyroline-5-carboxylate synthase) in the primed plants coincided with a significantly higher content of the amino acid measured in the leaves. These plants also accumulated particular dehydrin types, which may have contributed to the observed stress-relieving effect. The four-component hormonal mix applied by spraying or through the roots exerted similar stress-mitigating properties on soil-grown lettuce subjected to moderate drought.

In photolithography process, nanometer level precise, wavefront aberration models enable the machine to be able to meet the overlay (OVL) drift and critical dimension (CD) specifications. Software control algorithms take as input these models and correct any expected wavefront imperfections before reaching the wafer. In such way a near optimal image is exposed on the wafer surface. Optimizing the parameters of these models though, involves several time costly sensor measurements which reduce the throughput performance, in terms of exposed wafers per hour, of the machine. In that case, photolithography machines come across the trade-off between throughput and quality. Therefore one of the most common Optimal Experimental Design (OED) problems in photolithography machines (and not only) is how to choose the minimum amount of sensor measurements that will provide the maximum amount of information. Additionally, each sensor measurement corresponds to a point on the wafer surface and therefore we must measure uniformly around the wafer surface as well. In order to solve this problem, we propose a Sensor Marks Selection Algorithm which exploits Genetic Algorithms. The proposed solution first selects a pool of points that qualify as candidates to be selected in order to meet the uniformity constraint. Then, the point that provides the maximum amount of information, quantified by the Fisher based criteria of G, D and A-Optimality, is selected and added to the measurement scheme. This process though is considered "greedy", and for this reason Genetic Algorithms (GA) are exploited to further improve the solution. By repeating in parallel the "greedy" part several times we get an initial population that will be the input to our GA. This meta-heuristic approach outperforms the "greedy" approach significantly. The proposed solution is applied in a real life semiconductors industry use case and achieves interesting industry and academical results as well.

Background: Studies have demonstrated the link between vitamin D-related genetic variations and non-skeletal outcomes. We aimed to identify all available data on the association of vitamin D-related genetic variations with non-alcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible study must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3,495 articles were identified. After systematic review, twelve studies were in-cluded. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indi-cating the role of vitamin D in the pathogenesis of NAFLD.

Research with deuterium-depleted water (DDW) in the last two decades proved that deuterium/hydrogen ratio has a key role in cell cycle regulation and cellular metabolism. The present study aimed to investigate the possible effect of deuterium-depleted organic compounds (DDOC) alone and in combination with DDW on cancer growth in two in vivo mouse models. To produce DDOC, drinking water of laying hens was replaced with DDW (25 ppm) for 6 weeks, resulting in 60 ppm D level in dried egg yolk that was used as deuterium-depleted food additive. In one model, 4T1, a cell line with high metastatic capacity to the lung, was inoculated in the mice’s mammary pad. After three weeks of treatment with DDW and/or DDOC, the tumor volume in the lungs was smaller in all treated groups vs. controls with natural D level. Tumor growth and survival in mice transplanted with MCF-7 breast cancer cell line showed that the anticancer effect of DDW was enhanced by food containing the deuterium-depleted yolk. The study confirmed the importance of D/H ratio not only in consumed water but also in metabolic water produced by the mitochondria while oxidizing nutrient molecules. This is in line with the concept that initiation of cell growth requires the cells to generate a higher D/H ratio, but DDW, DDOC, or the naturally low-D lipids in a ketogenic diet, have significant effect on tumor growth by preventing the cells from raising D/H ratio to the threshold.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/ml). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

The terpolymers of N-vinylpyrrolidone (VP) with acrylic acid and triethylene glycol methacrylate were synthesized with more than 90% yield by radical copolymerization in ethanol from monomeric mixtures of different composition (98 : 2 : 2, 95 : 5: 2 and 98 : 2: 5). Their physical and chemical characteristics such as monomer composition, absolute molecular masses and hy-drodynamic radii in aqueous media at different temperature were determined. The temperature effect on the behavior of terpolymers in water and aqueous saline buffer solution with pH 7.4 has been studied and the ability of a copolymer enriched with dimethacrylates units was discovered to respond to a temperature change in these media. On the basis of terpolymers and linear polyvi-nylpyrrolidone (PVP), polymer compositions of hydrophobic dye methyl pheophorbide a, MPP, that is fluorescent in the red region of the spectrum, were obtained; the sizes of the polymer nanostructures of MPP in water were determined. The structures based on terpolymers were demonstrated to be more stable than MPP-PVP ones. It was carried out the quantum-chemical modelling of the possible structures of MPP-copolymer that formed as a result of intermolecular interaction between MPP and terpolymer’s chains; the possibility of the formation of hydrogen bonds between the donors of the electrons of terpolymer units and the proton donors of the MPP molecule was shown. Using the MTT test, it was established that copolymers of various compositions are low toxic for non-tumor Vero cells and HeLa tumor cells. It was shown that the cytotoxicity of polymer particles loaded with MPP for FetMSC and HeLa cells increased. Using fluorescence microscopy, the accumulation and distribution of polymer particles in non-tumor (FetMSC) and tumor (HeLa) cells was studied and an increase in the accumulation of MPP with both types of particles was shown.

Mediterranean Diet (MD), rich in minimally processed plant foods and in monounsaturated fats, but low in saturated fats, meat and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratio, lipids, and inflammation markers, and even prevents the development of fatal and non-fatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns on its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbioma.

To better understand how immunity develops against SARS-CoV-2 during the pandemic period of 2020 to 2022, we analyzed the immune response of a small group of university staff and students who were either infected or vaccinated. We investigated the levels of receptor-binding domain (RBD)-specific and nucleocapsid (N)-specific IgG and IgA antibodies in serum and saliva samples taken early (around 10 days after infection or vaccination) and later (around 1 month later), as well as N-specific T-cell responses. One patient who had been infected in 2020 developed serum RBD and N-specific IgG antibodies, but declined 8 months later, then mRNA vaccination in 2021 produced a higher level of anti-RBD IgG than natural infection. In the vaccination of naïve individuals, vaccines induced anti-RBD IgG, but it declined after 6 months. A third vaccination boosted the IgG level again, albeit to a lower level than after the second. In 2022, when the Omicron variant became dominant, familial transmission occurred even among vaccinated people. In infected individuals, the levels of serum anti-RBD IgG antibodies increased later, while anti-N IgG peaked earlier. The N-specific activated T cells expressing IFN- or CD107a were detected early. In saliva, SARS-CoV-2-specific IgG but not IgA was detected. Interestingly, two individuals showed a temporary peak in RBD- and N-specific IgA antibodies in their saliva on the second day after infection. Thus, SARS-CoV-2 infection triggers typical immune responses in humans against acute viral infections, but mucosal immune responses, which are temporarily induced early during infection, may be more important for protection than current intramuscular vaccines.

Vasculitis diseases include Kawasaki Disease (KD), Kawasaki Disease Shock Syndrome (KDSS), Multisystem Inflammatory Syndromes (MIS), Henoch-Schönlein purpura (HS) or IgA Vasculitis, and additional vasculitis diseases. These diseases are often preceded by infections or immunizations. Disease incidence rates are higher in children than adults. These diseases have been extensively studied, but understanding of the disease etiology remains to be established. Many studies have failed to demonstrate an association between these vasculitis diseases and vaccination. Here, the Vaccine Adverse Event Reporting System (VAERS) is used to demonstrate that, in certain rare cases, the number of cases of KD, MIS, and HS is higher than background following vaccination. These rare cases are predicted to occur in individuals with genetic risk factors who produce antibody titer levels above primary immune response level. Herein, the model of humoral immune response antibodies bound to antigens (pathogen or vaccine) creating immune complexes is proposed. These immune complexes are proposed to bind Fc receptors on immune cells and platelets resulting in cell activation and release of inflammatory molecules including histamine and serotonin. Immune complexes and inflammatory molecules including serotonin and histamine likely trigger vasculitis. Elevated serotonin and likely histamine drive initial vasoconstrictions disrupting blood flow. Increased blood flow pressure from cardiac capillary vasoconstrictions is predicted to trigger coronary artery aneurysms in some patients. For KDSS and MIS patients, these cardiac capillary vasoconstrictions are predicted to result in ischemia followed by ventricular dysfunction. Ongoing ischemia can result in long-term cardiac damage. Cases associated with pathogens are likely to have persistent infections triggering disease onset.

The mechanisms underlying the de novo regeneration of adventitious roots are still poorly understood, particularly in trees. In this study, we developed a system for studying different modulators of adventitious rooting (AR) at physiological and molecular levels by using for the first time leaves excised from chestnut microshoots. The rooting response of leaves was ontogenetic-stage dependent, and similar to that of the original microshoots. Initiation of root primordia and root development were inhibited by application of N-1-naphthyl-phthalamic acid (NPA), although the effect of this inhibitor of auxin polar transport (PAT) depended on the timing of application. Expression of CsSCL1, an auxin-inducible gene in juvenile and mature shoots during AR, was upregulated by auxin only in rooting-competent leaves during the novo root organogenesis and the expression was reduced by the NPA treatment. This inhibitory effect on gene expression was detected during reprograming of rooting competent cells towards root initials in response to auxin, indicating that PAT-mediated upregulation of CsSCL1 is required in the initial steps of AR in chestnut leaves. The localized expression of CsSCL1 in the quiescent center (QC) also suggests a role for this gene in the maintenance of meristematic competence and root radial patterning.

In present paper, spatial Minkowski Pythagorean Hodograph (MPH) curves are characterized with Rational Rotation Minimizing Frames (RRMFs). We define Euler-Rodrigues Frame (ERF) for MPH curves and by means of this concept, we reach the definition of MPH curves of type (n, m). Expressing the conditions provided by these curves in the form of Minkowski-Hopf map that we define, it is aimed to establish a connection with the Lorentz force which occurs during the process of Computer Numerical Control (CNC) type sinker Electronic Discharge Machines (EDMs). This approach is reinforced by split quaternion polynomials. Finally, we give conditons satisfied by MPH curves of low degree to be type (n, m) and construct illustrative examples.

Bone tissue engineering has developed significantly in recent years as the increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

In this work, kinetics of the reaction between 5,10,15,20-tetrakis(N-methylpyridium-4-yl)porphyrin and Ni2+ species were investigated in aqueous solution at 25 ±1 ºC in I = 0.10 M (NaNO3). Speciation of Ni2+ was carried out in I = 0.10 M (NaNO3) in order to provide the distribution of the Ni2+ species with different solution pH. The experimental data have been compared with the speciation diagram constructed from the values of hydrolysis constants of Ni2+ ion. Speciation data showed that the hexaaquanickel(II), [Ni(H2O)6]2+, ions take place in hydrolysis reactions through formation of [Ni(OH2)6-n(OH)n]2-n species with solution pH. Based on the speciation of Ni2+ and pH dependent rate constants, rate expression can be written as: d[Ni(TMPyP)4+]/dt = (k1[Ni2+(aq)] + k2[Ni(OH)+(aq)] + k3[Ni(OH)2o(aq)] + k4[Ni(OH)3-(aq)])[H2TMPyP4+], where k1, k2, k3 and k4 were found to be k1 = (0.62 ± 0.22) × 10-2; k2 = (3.60 ± 0.40) × 10-2; k3 = (2.09 ± 0.52) × 10-2, k4 = (0.53 ± 0.04) × 10-2 M-1s-1 at 25 ±1 °C, respectively. Kinetic results showed that monohydroxo, [Ni(H2O)5(OH)]+, is the most reactive among the [Ni(OH2)6-n(OH)n]2-n species. The enhanced reactivity has been ascribed to the formation of hydrogen bonding between oxygen atom of hydroxyl group of the [Ni(H2O)5(OH)]+ species and the pyrrolic hydrogen atom of the [H2TMPyP]4+. The rate of formation of [Ni(II)TMPyP]4+ complex was to be 3.99 × 10-2 M-1s-1 in I = 0.10 M, NaNO3 (25 ± 1 ºC). Ionic strength effect on the reaction rate is suggested that the net charge of the tetracationic porphyrin is to be +3.6 on the basis of Brønsted-Bjerrum equation. The UV-Vis and fluorescence data revealed that [Ni(II)TMPyP]4+ and H2(TMPyP)4+ interact with DNA, and UV-Vis results suggest that Ni(II)-porphyrin and free base porphyrin interact with DNA via outside binding with self-stacking and intercalation, respectively. Mechanism of kinetics of formation of the [Ni(II)TMPyP]4+ complex in aqueous medium is discussed. An investigation of application of the [Ni(II)TMPyP]4+ complex along with other metalloporphyrins such as Zn2+-, Ru2+-, Pt2+-, [Au(III)TMPyP]5+ as anti-COVID-19 agents is now in progress under international collaboration.

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

Historically, viral hepatitis is a considerable public health problem in Central Asian countries, which may have worsened after dissolution of the Soviet Union. However, up-to-date seroepidemiological studies are lacking. The aim of the present study was, therefore, to provide current estimates of seroprevalence of viral hepatitis in Kyrgyzstan, one of the economically least developed countries in the region. We conducted a population-based cross-sectional study in 2018 in the capital of Kyrgyzstan, Bishkek (n=1075). Participants, children and adults, were recruited from an outpatient clinic. Data were collected during face-to-face interviews. A blood sample (6 ml) was collected from each participant and tested with ELISA for the presence of serological markers for five viral hepatitides (A, B, C, D and E). Poststratification weighting was performed to obtain nationally representative findings. The overwhelming majority of the study participants were positive for anti-HAV (estimated seroprevalence, 75.3%; 95% confidence interval: 72.5–77.9%). The weighted seroprevalence estimates of HBsAg, anti-HCV and anti-HDV were 2.2% (1.5–3.3%), 3.8% (2.8–5.1%), and 0.40% (0.15–1.01%), respectively. Anti-HEV seropositivity was 3.3% (2.4–4.5%). Of the 33 HBsAg positive participants, five (15%) were anti-HDV positive. Our study confirms that Kyrgyzstan remains a high endemic country for hepatitis virus A and C infections. However, seroprevalences of HBV and HDV were lower than previously reported, and based on these data, the country could potentially be reclassified from high to (lower) intermediate endemicity. The observed anti-HEV seroprevalence resembles the low endemicity pattern characteristic of high-income countries.

Space-time evolution is briefly explained by using the 3-dimensional quantized space model (TQSM) based on the 4-dimensional (4-D) Euclidean space. The energy (mass), charges and absolute time are newly defined based on the 4-D Euclidean space. The photons and gravitons are understood as the 2-D space fluctuations along the space axes and 1-D time fluctuations along the time axis, respectively. This indicates that the electromagnetic (EM) and gravitational (G) waves can be unified into the so called gravityelectromagnetic (GEM) wave which has both space and time fluctuations. The photon with zero force fields is the 2EM wave because an EM wave corresponds to a charged fermion. The dark matter bosons, weak force bosons, strong force bosons are the 1-D time fluctuations which can be expressed by the G waves. This indicates that all five forces are unified by the GEM wave. It is called as the super unification theory in the present work. And the force carrying bosons and mesons are, for the first time, proposed as the possible candidates of the magnetic monopoles like the fermions and baryons are the electric monopoles. The signs of the magnetic charges quantized as q_m=cq are newly defined. The big bang is understood by the space-time evolution of the 4-D Euclidean space but not by the sudden 4-D Minkowski space-time creation. The big bang process created the matter universe with the positive energy and the partner anti-matter universe with the negative energy from the CPT symmetry.

To assist firefighters and other first responders to use their existing equipment for respiration during the COVID-19 pandemic without using single-use, low-supply, masks, this study outlines an open source kit to convert a 3M-manufactured Scott Safety self-contained breathing apparatus (SCBA) into a powered air-purifying particulate respirator (PAPR). The open source PAPR can be fabricated with a low-cost 3-D printer and widely available components for less than $150, replacing commercial conversion kits saving 85% or full-fledged proprietary PAPRs saving over 90%. The parametric designs allow for adaptation to other core components and can be custom fit specifically to fire-fighter equipment, including their suspenders. The open source PAPR has controllable air flow and its design enables breathing even if the fan is disconnected or if the battery dies. The open source PAPR was tested for air flow as a function of battery life and was found to meet NIOSH air flow requirements for 4 hours, which is 300% over expected regular use.

Multi-stakeholder based construction projects are subject to various risk factors due to dynamic business environments. These risks affect project activities which indirectly impact construction costs, resulting in delays and poor building quality. So, managing these project risks requires suitable risk mitigation strategies to evaluate and analyse their severity. Hence, risk evaluation and assessment of construction projects is a multi-criteria decision making (MCDM) problem. In present real-life problems, evaluation of project risks is often uncertain and even incomplete, and the prevailing methodologies fail to handle such situations. To address the problem, this paper extends the analytical network process (ANP) methodology in the D number domain to handle three types of ambiguous evaluations, viz. complete, uncertain, and incomplete, and assesses the weight of risk criteria. The D number based approach overcomes the deficiencies of the exclusiveness hypothesis and completeness constraint of Dempster-Shafer (D-S) theory. Here, preference ratings of the decision matrix for each decision-maker are determined using a D number extended consistent fuzzy preference relation (D-CFPR). An extended multi-attributive border approximation area comparison (MABAC) method in D number is then developed to rank and select the best alternative risk response strategy. Finally, an illustrative example from construction sector is presented to check the feasibility of the proposed approach. For checking the reliability of alternative ranking, a comparative analysis is performed with different MCDM approaches (D-COPRAS, D-ARAS, D-MABAC, and D-TOPSIS). Based on different criteria weights, a sensitivity analysis of obtained ranking of the hybrid D-ANP-MABAC model is performed for verify the robustness of the proposed method.

Evidence suggests that COVID-19 infection increases the risk of type 1 (T1D) and type 2 diabetes (T2D). Diabetes, in turn, increases COVID-19 susceptibility and contributes to increased COVID-19 morbidity and mortality. Oxidative stress (OxS) has emerged as a common factor driving the pathogenesis of diabetes and COVID-19 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). The mechanistic links between OxS, T2D, and COVID-19 have primarily been studied in adults and will be summarized in this review. However, we suggest that studying these interconnections in children and young adults is critical since early intervention is optimal for improving outcomes. At the height of the pandemic, COVID-19 was a leading cause of death in children and young people, and people in this age group are as susceptible to COVID-19 as adults and the elderly. Glutathione (GSH) is the primary water-soluble intracellular antioxidant and can be deficient in both diabetes and COVID-19. GSH is a tripeptide containing cysteine (CYS), glutamic acid (GLU), and glycine (GLY). Strategies to increase GSH levels may be beneficial in helping to manage COVID-19-induced diabetes as well as diabetes-induced COVID-19 risk. Dietary supplementation with GlyNAC may be optimal since it contains two metabolic GSH precursors, i.e., n-acetyl-l-cysteine (NAC) and GLY.

The inability to delineate a unified physical ontology that accounts simultaneously for the laws of special relativity and the results of quantum experiments has been a defining problem in physics for more than 100 years. This analysis addresses the problem by positing an ontic, mixed ontology composed of a “discrete” 4D spacetime and a physical, ultra-high dimensional (3 x N) “Planck Space.” Together, Planck Space and the three spatial dimensions of 4D spacetime form a tightly integrated ((3 x N) + 3) hyperspace (the “Dual Ontology”). Critically, the Dual Ontology’s structure replaces 1) the continuous, differentiable manifold of 4D spacetime with a discrete 4D spacetime and 2) mathematical 3N configuration spaces with a physical (3 x N) Planck Space. Moreover, the Dual Ontology is structurally and dynamically predicated on the one-to-one mapping and identity between the discrete spatial units that simultaneously form 4D spacetime and Planck Space. The one-to-one mapping and identity of the discrete spatial units support an integrated quantum dynamics based upon the dynamic evolution of single and N-body quantum states in 4D spacetime in full compliance with the laws of special relativity and the instantaneous collapse of all quantum states in an ontic Planck Space, where special and general relativity and more generally, 4D spacetime’s laws of physics, do not apply.

In this article, the multitouch option, also called the n  touch option (or the “baseball” option when n  3 ) is analyzed and valued in closed form. This is a kind of barrier option that sets a gradual knockout / knock-in mechanism based on the number of times the underlying asset has crossed a predefined barrier in various time intervals before expiry. The higher the number of predefined time intervals during which the barrier has been touched, the lower the value of a knock-out contract at expiry, and conversely for a knock-in one. Multitouch options can be viewed as an extension of step barrier options, preserving the ability of the latter to adjust the exposure to risk over time, while eliminating the notorious danger of “sudden death” that holders of step barrier options are faced with. Unlike occupation time derivatives, the payoff at expiry does not depend on the amount of time spent outside the authorized range, but on the number of passages beyond the authorized range.

Despite huge effort has been devoted to the design of the initiators and reaction conditions, it remains challenging to synthesize high molecular weight polypeptides with conventional solution phase synthesis. In this work, surface-initiated vapor deposition polymerization (SI-VDP) was utilized to graft synthetic polypeptides poly (γ-benzyl L-glutamate) (PBLG) from polystyrene (PS) resin beads by ring-opening polymerization of N-carboxyanhydrides (NCAs). It was demonstrated for the first time that high molecular weight bulk PBLG (> 500,000) could be readily obtained within one hour via solvent-free synthetic method which paves the way for the synthesis of copolypeptides with high molecular weight.

My innovative entropy measure, Ismail entropy, namely, (IE) is an ultimate generalization to numerous generalized entropies within the literature. The fractal dimension of IE is identified in this paper. On another applicative note, this paper offers some potential applications of fractal dimension to smart cities. The paper ends with closing remarks combined with some challenging open problems and the next phase of research.

(R)-1-(4-Amino-3,5-dichlorophenyl)-2-bromoethan-1-ol has been synthesised in 93% enantiomeric excess (ee) by asymmetric reduction of the corresponding ketone catalysed by a ketoreductase and NADPH as the co-factor in DMSO. (S)-N-(2,6-Dichloro-4-(1-hydroxyethyl)phenyl)acetamide has been synthesised in >98% ee by the same system. Both synthons are potential precursors for clenbuterol enantiomers. Clenbuterol is a β₂-agonist used in veterinary treatment of asthma in several countries. The drug is listed on the World Anti-doping Agency’s Prohibited list due to its effect on increased protein synthesis in the body. However, racemic clenbuterol has recently been shown to reduce the risk of Parkinson’s disease. In order to reveal which one (or both) of the enantiomers that cause this effect, the pure enantiomers need to be studied separately. Our biocatalytic approach in order to obtain enantiopure clenbuterol should be applicable to industrial scale.

Bovine Respiratory Disease Complex, a complex respiratory ailment in cattle, results from a combination of viral and bacterial factors, compounded by environmental stressors such as overcrowding, transportation, and adverse weather conditions. Its impact extends beyond mere health concerns, posing significant economic threats to the cattle industry. This study presents an extensive investigation into viral pathogens associated with BRDC in Serbian cattle, utilizing serum samples and nasal swabs. A cross-sectional study was conducted in 2024 across 65 randomly selected dairy farms in Serbia, excluding vaccinated farms. Farms were categorized by livestock count: small (≤50 animals), medium-sized (51-200 animals), and large (>200 animals). Serum samples from adult cattle older than 24 months were tested for antibodies against BVDV, BHV-1, BRSV, and BPIV3. Nasal swab samples from animals with respiratory signs were tested using PCR for viral genome detection. Results showed seropositivity for all four viruses across all farms, with BPIV3 exhibiting universal seropositivity. Medium-sized and large farms demonstrated higher seropositivity for BRSV and BHV-1 compared to small farms (p<.05). True seroprevalence estimates at the animal level were 84.29% for BRSV, 54.08% for BVDV, 90.61% for BHV-1, and 84.59% for BPIV3. PCR analysis of nasal swabs revealed positive detections for BRSV (20%), BHV-1 (1.7%), BVDV (8%), and BPIV3 (10.9%). Influenza D virus was not found in any of samples. This study provides critical insights into the prevalence and circulation of viral pathogens associated with BRDC in Serbian cattle, emphasizing the importance of surveillance and control measures to mitigate the impact of respiratory diseases in cattle populations.

Multiple myeloma (MM) accounts for about 10 to 15% of all diagnosed hematologic malignancies and about 1-2% of all cancer cases. Approximately 80-90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the levels of selected bone turnover markers associated with the Wnt pathway in patients with MM. Results from 35 patients divided into training (NW and IF NW) and non-training (IF and control) groups were included in the analysis. A 6-week training cycle involving 60-minute workouts 3 times a week was conducted. Body mass and composition and the levels of: vitamin D, calcium and phosphorus, beta2-microglobulin and albumin were examined before and after completion of training cycle. Markers of bone turnover were also determined: sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), osteoprotegrin (OPG), osteopontin (OPN) and Tartrate-resistant acid phos-phatase 5b (TRACP 5b). There was no negative effect of IF or combined training and fasting on the nutritional status of the patients (the level of albumines was unchanged). Both training groups showed an increase in serum concentrations of the active metabolite of vitamin D (IF NW and NW: p=0.001 and p=0.022, re-spectively). The change in the concentration of this vitamin negatively correlated with the con-centration of TRACP 5b (r=-0.413, p=0.014). Evaluating the concentrations of markers related to bone turnover, a reduction in the concentrations of SOST (time: p=0.026, time vs. group: p=0.033) and TRACP 5b (time: p

Syringomyelia can be associated with multiple etiologies. The treatment of the underlying causes is the first-line therapy, however, a direct approach to the syrinx is accepted as rescue treatment. Any direct intervention on the syrinx requires a myelotomy, posing a significant risk of iatrogenic spinal cord (SC) injury. Intraoperative neurophysiological monitoring (IONM) is crucial to detect and prevent surgically induced damage in neural SC pathways. We retrospectively reviewed the perioperative and intraoperative neurophysiological data and perioperative neurological examinations in ten cases of syringomyelia surgery. All monitored modalities remained stable throughout the surgery in six cases, correlating with no new postoperative neurological deficits. In two patients, significant transitory attenuation, or loss of motor evoked potentials (MEPs), were observed and recovered after a corrective surgical maneuver, with no new postoperative deficit. In two cases, a significant MEP decrement was noted, which lasted until the end of the surgery and was associated with postoperative weakness. A transitory train of neurotonic electromyography (EMG) discharges was reported in one case, the surgical plan was adjusted and the patient showed no postoperative deficit. The dorsal nerve roots were stimulated and identified in the seven cases where the myelotomy was performed via the dorsal root entry zone. Dorsal column mapping guided the myelotomy entry zone in four cases. In conclusion, multimodal IONM is feasible and reliable and may help prevent iatrogenic SC injury during syringomyelia surgery.

Age-related macular degeneration is one of the most common causes of blindness, and the incidence exhibits profound racial bias, occurring most frequently in Caucasians. A primary cell type affected in the disease is the retinal pigment epithelium, but the etiology is unclear. The end 10% of the photoreceptor outer segments are shed each day, and the underlying retinal pigment epithelium engulfs, digests, and recycles molecules back to the sensory retina. In previous work, we showed that GPR143 signaling in response to L-DOPA may be effective in the prevention or delay of age-related macular degeneration. In this study, we explore a novel potential effector of GPR143 signaling, that of outer segment uptake and digestion. Using isolated outer segments, labelled with a pH-sensitive marker to fluoresce in lysosomes, we show that GPR143 signaling does not impact outer segment uptake, but does have a significant effect on subsequent degradation. Interestingly, GPR143 signaling did not affect the digestive capacity of the cells, marked by total proteolytic capacity and cathepsin D activity. Rather, our data suggest GPR143 improved endosomal trafficking efficiency of the phagocytosed outer segments to the lysosome. This result is similar to the effect we previously reported for GPR143 on exosome release from the endosomal compartment. Our data illustrate that GPR143 is active in endosomal traffic A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

The absolute time and relative time are defined in terms of the 4-D Euclidean space. Our universe is the 3-D x₁x₂x₃ quantized photon space which follows the absolute time simultaneity when the universe moves along the absolute time axis of ct. The length expansion of Dx = gDx₀ is derived under the condition of the absolute time (ct) simultaneity. From the similarity between this length expansion of Dx = gDx₀ and the energy increasing of E = gE₀, it is assumed that the energy is proportional to the particle size of Dx. The extension of this assumption to the 4-D Euclidean space gives the new definition that the particle energy (E) is the 4-D volume. Then, the particle mass energy is defined as E= mc² = cDtDV = gE₀. The masses of the elementary particles are originated from the 4-D warped volume of the photon space because the particle is the warped photon space with the velocity of v < c. Therefore, the Higgs boson concept in the standard model (SM) is not needed in the present 3-D quantized space model (TQSM). The scalar boson with the spin of zero, photon with the spin of 1 and graviton with the spin of 2 are the two-boson states. Therefore, the observed Higgs boson is reinterpreted as the two-boson state of the scalar boson with the spin of zero. The cosmic muon observation and twin paradox are explained by using the absolute time and relative time. The relative time is the observed time in the twin paradox and cosmic muon observation. In the twin paradox, a person who travels the long distance is more aged than a person on the earth in terms of the relative time ages because of the space and time conversion effect (STCE effect) of the moving space distance (x). But twins are in the same ages in terms of the absolute time without STCE effect. The fast-moving cosmic muon has the expanded half-life from the time expansion of the relative time. Also, the quantum entanglement and Pauli exclusion principle are explained. The quantum base of the photon space line connects two entangled particles. Two particles and quantum base system is fluctuated along the absolute time axis by the time clicking when one particle is measured. Another particle is instantly selected by the time clicking. This is called as the quantum entanglement. The photons which are the flat photon space with the constant speed of c along the space axis and absolute time axis have the 4-D photon velocity of c_eff = 2^0.5 c. Total 10-D Euclidean space including three 3-D quantized spaces and one absolute time axis is required for the electric charges (EC), lepton charges (CC) and color charges (CC) of the elementary particles. The 3-D photon space is very stiff along the absolute time (ct) axis and very soft along the space axes. The Coulomb force through the photons (2EM waves) of the space fluctuations is much stronger than the Gravitational force through the gravitons (G waves) of the time fluctuations between two electrons.

Space-time evolution of our universe is explained by using the 3-dimensional quantized space model (TQSM) based on the 4-dimensional (4-D) Euclidean space. The energy (E = cDtDV), charges and energy density (|q| = r = cDt) and absolute time (ct) are newly defined based on the 4-D Euclidean space. The photon flat space with the constant energy density of r = cDt_q is proposed as the dark energy (DE). The dark energy is separated into the n DE and photon DE which create the new photon spaces with the constant energy density of r = cDt_q. The v DE is from the n pair production by the CPT symmetry and the photon DE is from the photon space pair production by the T symmetry. The vacuum energy crisis and Hubble’s constant puzzle are explained by the photon space with the n DE and photon DE. The big bang and inflation of the primary black hole is connected to the accelerated space expansion and big collapse of the photon space through the universe evolution. The big bang from the nothing is the pair production of the matter universe with the positive energy and the partner anti-matter universe with the negative energy from the CPT symmetry. Our universe is the matter universe with the negative charges of electric charge (EC), lepton charge (LC) and color charge (CC). This first universe is made of dark matter -, lepton -, and quark - primary black holes with the huge negative charges which cause the Coulomb repulsive forces much bigger than the gravitational forces. The huge Coulomb forces induce the inflation of the primary black holes, that decay to the super-massive black holes and particles.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Article explores participant specific study of muscle inherehit dynamics hidden inside the diognostic electromyography (D-EMG) signals during load pull exercises, aiming to uncover underlying patterns and nonlinear behaviors. Employing a multi-step analytical framework, the study first evaluates signal stationarity through Quantile-Quantile (Q-Q) plot and surrogate data analyses, revealing insights into signal stability. Subsequent use of phase space reconstruction techniques exposes intrinsic dynamics within the EMG signals, visualized through Poincar´e maps, elucidating attractor geometry and system dynamics. Histogram analysis further dissects the Poincar´e maps, offering insights into signal behavior relative to physiological processes. Additionally, the study quantifies the largest Lyapunov exponent from the Poincar´e maps, providing a measure of dynamical complexity within the muscle EMG signals during load pull exercises. By integrating these methods, this research sheds light on the nuanced interplay between EMG signals and muscle activity during dynamic exercises, offering valuable insights for rehabilitation strategies.

It has been more than a century since Erlang published his paper in 1909. The classical queueing system for the M/D/c queue has been investigated by many authors. The key is to find the roots of an equation using explicit or numerical methods. We present an alternate form of explicit solution(s) of this/these root(s) using the Lambert-W function in this paper. In addition, the unsaturated probabilities of the number of customers in the system is derived explicitly in terms of this/these root(s). Finally, the mean number of customers in the system and the mean queueing delay are obtained from these probabilities. The exact queueing delay formula for the M/D/c queue is expressed in closed-form in terms of the root(s). Numerical results show that they are in excellent agreement with the numerical results published by Seelen, Tijms and Van Hoorn.

Abstract: In order to accelerate deployment of distributed recycling by providing low-cost feed stocks of granulated post-consumer waste plastic, this study analyzes an open source waste plastic granulator system. It is designed, built and tested for its ability to convert post-consumer waste, 3-D printed products and waste into polymer feedstock for recyclebots of fused particle/granule printers. The technical specifications of the device are quantified in terms of power consumption (380 to 404W for PET and PLA, respectively) and particle size distribution. The open source device can be fabricated for less than USD$2000 in materials. The experimentally-measured power use is only a minor contribution to the overall embodied energy of distributed recycling of waste plastic. The resultant plastic particle size distributions were found to be appropriate for use in both recyclebots and direct material extrusion 3-D printers. Simple retrofits are shown to reduce sound levels during operation by 4dB-5dB for the vacuum. These results indicate that the open source waste plastic granulator is an appropriate technology for community, library, makespace, fab lab or small business-based distributed recycling.

Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

Abstract: Extensive research shows nurses’ work environment to be particularly stressful. This study develops, explores, and psychometrically tests a new profession specific ques-tionnaire identifying generalized and specific resistance resources, that make it possible to measure resources to manage work-related stress. An exploratory study design was em-ployed. The questionnaire was developed inspired by the MEASURE approach and the salutogenic theory of health. Building on the results from a literature review of nursing re-search and salutogenesis, supplemented by twelve interviews with hospital nurses, an item pool was generated. A first version was pilot tested in a group of nurses who were studying to become specialist nurses. A second version of the questionnaire was psycho-metrically tested on nurses in close patient care (n = 475), analysed using Principal Com-ponent Analysis as the extracting technique to identify the underlying structure of the questionnaire. The Principal Component Analysis revealed a four-component model of 19 items. “Manageability as a resource for handling the workload” was the strongest compo-nent, accounting for 21 % of the explained variance. “Contacts with patients as resources for nurses’ job satisfaction” (17.8 %). “Professional attitudes are labelled as resources to nursing” (15 %). “Colleagues are important resources for remaining in the nursing profes-sion” (11 %). The structure of the questionnaire indicates its usefulness in clinical practice for measuring resistance resources.

We present results on the spontaneous crystallization of freely-jointed polymers of hard spheres obtained in an unprecedentedly long Monte Carlo (MC) simulation on a system of 54 chains of 1000 monomers. Starting from a purely amorphous configuration and after a transitory dominance of the hexagonal closed packed (HCP) polymorph, the system crystallizes in a final, stable, face centered cubic (FCC) crystal of very high perfection. Through refined metrics we gauge the degree of ordering and identify the regions of the phase transition and the corresponding morphologies. An analysis of chain conformational characteristics, of the spatial distribution of monomers and of the volume accessible to them shows that the phase transition is caused by an increase in translational entropy that is larger than the loss of conformational entropy of the chains in the crystal compared to the amorphous state. Polymer chains in the crystal adopt ideal random walk statistics as their great length renders local conformational details, imposed by the geometry of the FCC crystal, irrelevant.

Both SARS-CoV-2 and SARS-CoV initially appeared in China and spread to other parts of the world. SARS-CoV-2 has generated a COVID-19 pandemic causing more than 6 million human deaths worldwide while the SARS outbreak quickly ended in six months with a global total of 774 reported deaths. One of the factors contributing to this stunning difference in the outcome between these two outbreaks is the inaccuracy of the RT-qPCR tests for SARS-CoV-2, which generated a large number of false-negative and false-positive test results that have misled patient management and public health policy-makers. This article presented Sanger sequencing evidence to show that the RT-PCR diagnostic protocol established in 2003 for SARS-CoV can in fact detect SARS-CoV-2 accurately due to the well-known nonspecific PCR amplification of DNAs with similar sequences. Using nested RT-PCR followed by Sanger sequencing to retest 50 patient samples collected in January, 2022 and sold as RT-qPCR positive reference confirmed 21 (42%) were false-positive. Although the other 29 positive isolates were categorized as Omicron variant by partial sequencing of the N gene, and the RBD and the NTD of the S gene, 9 (31%) showed focal to complete sequencing failure in the S gene segments due to multi-allelic SNPs. During the course of the study, an Omicron variant isolate containing a BA.1 NTD and a BA.2 RBD in its S gene was also detected. Routine partial S gene sequencing of all PCR-positive samples can timely discover multi-allelic SNPs and viral recombination in the circulating variants for investigation of their impacts on vaccine efficacies, therapeutics and diagnostics.

Diarrhoea caused by enterotoxigenic Escherichia coli is one of the leading causes of mortality in children under five years of age and is a great burden on developing countries. The major virulence factor of the bacterium is the heat-labile enterotoxin (LT), a close homologue of the cholera toxin. The toxins bind to carbohydrate receptors in the gastrointestinal tract, leading to toxin uptake and, ultimately, to severe diarrhoea. Previously, LT from human- and porcine-infecting ETEC (hLT and pLT, respectively) were shown to have different carbohydrate-binding specificities, in particular with respect to N-acetyllactosamine-terminating glycosphingolipids. Here, we probed eleven single-residue variants of the heat-labile enterotoxin with surface plasmon resonance spectroscopy and compared the data to the parent toxins. In addition we present a 1.45 Å crystal structure of pLTB in complex with branched Lacto-N-neohexaose (Galbeta4GlcNAcbeta6[Galbeta4GlcNAcbeta3]Galbeta4Glc). The largest difference in binding specificity is caused by mutation of residue 94, which links the primary and secondary binding sites of the toxins. Residue 95 (and to a smaller extent also residues 7 and 18) also contribute, whereas residue 4 shows no effect on monovalent binding of the ligand and may rather be important for multivalent binding and avidity.

Using coherent optical detection and digital signal processing, laser phase noise and equalization enhanced phase noise can be effectively mitigated using the feed-forward and feed-back carrier phase recovery approaches. In this paper, theoretical analyses of feed-back and feed-forward carrier phase recovery methods have been carried out in the long-haul high-speed n-level phase shift keying (n-PSK) optical fiber communication systems, involving a one-tap normalized least-mean-square (LMS) algorithm, a block-wise average algorithm, and a Viterbi-Viterbi algorithm. The analytical expressions for evaluating the estimated carrier phase and for predicting the bit-error-rate (BER) performance (such as the BER floors) have been presented and discussed in the n-PSK coherent optical transmission systems by considering both the laser phase noise and the equalization enhanced phase noise. The results indicate that the Viterbi-Viterbi carrier phase recovery algorithm outperforms the one-tap normalized LMS and the block-wise average algorithms for small phase noise variance (or effective phase noise variance), while the one-tap normalized LMS algorithm shows a better performance than the other two algorithms for large phase noise variance (or effective phase noise variance). In addition, the one-tap normalized LMS algorithm is more sensitive to the level of modulation formats.

Nutrition, diabetes, and mental disorders are interconnected and significantly impact an individual's overall health and well-being. This comprehensive review aims to explore the complex interplay between nutrition, diabetes, and mental disorders, highlighting the latest research findings in this field. While the influence of nutrition on the development and management of both diabetes and mental disorders is widely recognized, there remains a gap in understanding the intricate interplay between nutrition, mental health, and diabetes. Diabetes is associated with an increased risk of mental disorders, including depression, anxiety, and cognitive decline. Mental disorders can also contribute to the development of diabetes through various mechanisms including increased stress, poor self-care behaviors, and adverse effects on glucose metabolism. Thus, the mechanisms linking nutrition, diabetes, and mental disorders are complex and multi-factorial. Inflammation, oxidative stress, gut microbiota alterations, and neuroendocrine dysregulation have emerged as potential pathways that may mediate the relationship between nutrition, diabetes, and mental disorders. Additionally, deficiencies in essential nutrients such as omega-3 fatty acids, vitamin D, B vitamins, zinc, chromium, magnesium, and selenium have been implicated in the pathogenesis of both diabetes and mental disorders. Our findings indicate that the use of personalized dietary interventions and targeted nutrient supplementation can improve metabolic and mental health outcomes in patients with type 2 diabetes.

Space-time evolution is briefly explained by using the 3-dimensional quantized space model (TQSM) based on the 4-dimensional (4-D) Euclidean space. The energy (E=cDtDV), charges (|q|= cDt) and absolute time (ct) are newly defined based on the 4-D Euclidean space. The big bang is understood by the space-time evolution of the 4-D Euclidean space but not by the sudden 4-D Minkowski space-time creation. The big bang process created the matter universe with the positive energy and the partner anti-matter universe with the negative energy from the CPT symmetry. Our universe is the matter universe with the negative charges of electric charge (EC), lepton charge (LC) and color charge (CC). This first universe is made of three dark matter -, lepton -, and quark - primary black holes with the huge negative charges which cause the Coulomb repulsive forces much bigger than the gravitational forces. The huge Coulomb forces induce the inflation of the primary black holes, that decay to the super-massive black holes. The dark matter super-massive black holes surrounded by the normal matters and dark matters make the galaxies and galaxy clusters. The spiral arms of galaxies are closely related to the decay of the 3-D charged normal matter black holes to the 1-D charged normal matter black holes. The elementary leptons and quarks are created by the decay of the normal matter charged black holes, that is caused by the Coulomb forces much stronger than the gravitational forces. The Coulomb forces are very weak with the very small Coulomb constants (k₁(EC) = k_dd(EC) ) for the dark matters and very strong with the very big Coulomb constants (k₂(EC) = k_nn(EC)) for the normal matters because of the non-communication of the photons between the dark matters and normal matters. The photons are charge dependent and mass independent. But the dark matters and normal matters have the similar and very weak gravitational forces because of the communication of the gravitons between the dark matters and normal matters. The gravitons are charge independent and mass dependent. Note that the three kinds of charges (EC, LC and CC) and one kind of mass (m) exist in our matter universe. The dark matters, leptons and quarks have the charge configurations of (EC), (EC,LC) and (EC,LC,CC), respectively. Partial masses of elementary fermions are calculated, and the proton spin crisis is explained. The charged black holes are not the singularities.

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

For Visually impaired People (VIPs), the ability to convert text to sound can mean a new level of independence or the simple joy of a good book. With significant advances in Optical Character Recognition (OCR) in recent years, a number of reading aids are appearing on the market. These reading aids convert images captured by a camera to text which can then be read aloud. However, all of these reading aids suffer from a key issue – the user must be able to visually target the text and capture an image of sufficient quality for the OCR algorithm to function – no small task for VIPs. In this work, a Sound-Emitting Document Image Quality Assessment metric (SEDIQA) is proposed which allows the user to hear the quality of the text image and automatically captures the best image for OCR accuracy. This work also includes testing of OCR performance against image degradations, to identify the most significant contributors to accuracy reduction. The proposed No-Reference Image Quality Assessor (NR-IQA) is validated alongside established NR-IQAs and this work includes insights into the performance of these NR-IQAs on document images.

As SARS-CoV-2 continues to spread among human populations, genetic changes occur and accumulate in the circulating virus. Some of these genetic changes have caused amino acid mutations, including deletions, which may have potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics. Considerable efforts have been made to categorize the amino acid mutations of the angiotensin-converting enzyme 2 (ACE2) receptor binding domain (RBD) of the spike (S) protein along with certain mutations in other regions within the S protein as specific variants in an attempt to study the relationship between these mutations and the biological behavior of the virus. However, the currently used whole genome sequencing surveillance technologies can test only a small fraction of the positive specimens with high viral loads and often generate uncertainties in nucleic acid sequencing that needs additional verification for precision determination of mutations. This article introduces a generic protocol to routinely sequence a 437-bp nested RT-PCR cDNA amplicon of the ACE2 RBD and a 490-bp nested RT-PCR cDNA amplicon of the N-terminal domain (NTD) of the S gene for detection of the amino acid mutations needed for accurate determination of all variants of concern and variants of interest according to the definitions published by the U.S. Centers for Disease Control and Prevention. This protocol was able to amplify both nucleic acid targets into cDNA amplicons to be used as templates for Sanger sequencing on all 16 clinical specimens that were positive for SARS-CoV-2.

C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.

Centrifuges are commonly required devices in medical diagnostics facilities as well as scientific laboratories. Although there are commercial and open source centrifuges, costs of the former and required electricity to operate the latter, limit accessibility in resource-constrained settings. There is a need for low-cost, human-powered, verified and reliable lab-scale centrifuge. This study provides the designs for a low-cost 100% 3-D printed centrifuge, which can be fabricated on any low-cost RepRap-class fused filament fabrication (FFF) or fused particle fabrication (FPF)-based 3-D printer. In addition, validation procedures are provided using a web camera and free and open source software. This paper provides the complete open source plans including instructions for fabrication and operation for a hand-powered centrifuge. This study successfully tested and validated the instrument, which can be operated anywhere in the world with no electricity inputs obtaining a radial velocity of over 1750rpm and over 50N of relative centrifugal force. Using commercial filament the instrument costs about US$25, which is less than half of all commercially available systems; however, the costs can be dropped further using recycled plastics on open source systems for over 99% savings. The results are discussed in the contexts of resource-constrained medical and scientific facilities.

The following system of equations {x_1 \cdot x_1=x_2, x_2 \cdot x_2=x_3, 2^{2^{x_1}}=x_3, x_4 \cdot x_5=x_2, x_6 \cdot x_7=x_2} has exactly one solution in ({\mathbb N}\{0,1})^7, namely (2,4,16,2,2,2,2). Hypothesis 1 states that if a system of equations S \subseteq {x_i \cdot x_j=x_k: i,j,k \in {1,...,7}} \cup {2^{2^{x_j}}=x_k: j,k \in {1,...,7}} has at most five equations and at most finitely many solutions in ({\mathbb N}\{0,1})^7, then each such solution (x_1,...,x_7) satisfies x_1,...,x_7 \leq 16. Hypothesis 1 implies that there are infinitely many composite numbers of the form 2^{2^{n}}+1. Hypotheses 2 and 3 are of similar kind. Hypothesis 2 implies that if the equation x!+1=y^2 has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(4,5),(5,11),(7,71)}. Hypothesis 3 implies that if the equation x(x+1)=y! has at most finitely many solutions in positive integers x and y, then each such solution (x,y) belongs to the set {(1,2),(2,3)}. We describe semi-algorithms sem_j (j=1,2,3) that never terminate. For every j \in {1,2,3}, if Hypothesis j is true, then sem_j endlessly prints consecutive positive integers starting from 1. For every j \in {1,2,3}, if Hypothesis j is false, then sem_j prints a finite number (including zero) of consecutive positive integers starting from 1.

We point out an inconsistency in Newton's equations of celestial mechanics. A set of differential equations implied by Newton's equations are shown to be free of this inconsistency. We then investigate the integrals of motion associated with this relative difference system.

In this paper, we study the effect of parasitic channel on electrical characteristics and power consumptions of vertically stacked gate-all-around (GAA) silicon nanosheet (NS) MOSFETs of the bulk and silicon-on-insulator (SOI) substrates. Through deliberate control of the bottom parasitic channel coverage, we systematically assess its influence on DC, AC, and RF characteristics including power consumption. The observed findings highlight a significant differentiation among the bottom parasitic channels: GAA (i.e., control sample with 100% coverage), omega-shaped gate NS (70% and 80% coverages), and FinFET (60% coverage). Compared with the device with a 60% coverage channel, the device with a 100% coverage channel possesses 3520% and 8030% normalized leakage current improvement for both NFET and PFET under the bulk substrate, respectively. Compared with bulk-substrate devices, the SOI-substrate devices further significantly improve the leakage current. Due to enhanced off-state current leakages in the 100% covered bulk-substrate device, the static power demonstrates a notable improvement (about 98.1%), compared to 60% covered devices. Hence, the utilization of a 60% covered channel will result in a degradation of both device and circuit performance. The observation of GAA NS MOSFET indicates that an increase in the bottom parasitic channel coverage ratio leads to a positive impact on power consumption and leakage currents. The examination presented here is useful in the fabrication of stacked GAA NS MOSFETs.

This work introduces the mathematical framework of the novel “First-Order Comprehensive Adjoint Sensitivity Analysis Methodology for Neural Ordinary Differential Equations (1st-CASAM-NODE)” which yields exact expressions for the first-order sensitivities of NODE decoder-responses to the NODE parameters, including encoder initial conditions, while enabling the most efficient computation of these sensitivities. The application of the 1st-CASAM-NODE is illustrated by using the Nordheim-Fuchs reactor dynamics/safety phenomenological model, which is representative of physical systems that would be modeled by NODE while admitting exact analytical solutions for all quantities of interest (hidden states, decoder outputs, sensitivities with respect to all parameters and initial conditions, etc.). This work also lays the foundation for the ongoing work on conceiving the “Second-Order Comprehensive Adjoint Sensitivity Analysis Methodology for Neural Ordinary Differential Equations (2nd-CASAM-NODE)” which aims at yielding exact expressions for the second-order sensitivities of NODE decoder-responses to the NODE parameters and initial conditions while enabling the most efficient computation of these sensitivities.

In the face of the burgeoning electricity demands and the imperative for sustainable development amidst rapid industrialization, this study introduces a dynamic and adaptable framework suitable for policy-makers and renewable energy experts working on integrating and optimizing renewable energy solutions. While using a case study representative model for Sub-Saharan Africa (SSA) to demonstrate the challenges and opportunities present in introducing optimization methods to bridge power supply deficits and the scalability of the model to other regions, this study presents an agile multi-criteria decision tool that pivots on four key development phases, advancing upon established methodologies and pioneering refined computational techniques, to select optimal configurations from a set of Policy Decision Making Metrics (PDM-DPS). Central to this investigation lies a rigorous comparative analysis of variants of three advanced algorithmic approaches: Swarm-Based Multi-objective Particle Swarm Optimization (MOPSO), Decomposition-Based Multi-objective Evolutionary Algorithm (MOEA/D), and Evolutionary-Based Strength Pareto Evolutionary Algorithm (SPEA2). These are applied to a grid-connected hybrid system, evaluated through a comprehensive 8760-hour simulation over a 20-year planning horizon. The evaluation is further enhanced by a set of refined Algorithm Performance Evaluation Metrics (AL-PEM) tailored to the specific constraints. The findings not only underscore the robustness and consistency of the SPEA2 variant over 15 runs of 200 generations each, which ranks first on the AL-PEM scale but also validate the strategic merit of combining multiple technologies and empowering policymakers with a versatile toolkit for informed decision-making.

This article explores the cutting-edge advancement of gypsum and cement building boards infused with shape-stabilized n-octadecane, an organic phase change material (PCM). The primary focus is on improving energy efficiency and providing electromagnetic interference (EMI) shielding capabilities for contemporary buildings. The research investigates the integration of these materials into construction materials, using red-mud Carbon Foam as a stabilizer for n-octadecane (OD@CCF). Various analyses, including microstructural examination, porosity assessment, and additive dispersion, were conducted using X-ray microtomography and density measurements. Thermal conductivity measurements demonstrated the enhancement of composite boards as the OD@CCF content increased, while mechanical tests indicated an optimal additive content of up to 20%. The thermal-regulated capabilities of these advanced panels were evaluated in a custom-designed room model equipped with a homemade environmental chamber, illustrating a consistent temperature environment during heating and cooling cycles. The incorporation of OD@CCF into cement boards exhibited improved thermal energy storage properties. Moreover, the examined composite boards displayed efficient electromagnetic shielding performance within the frequency range of 3.2–7.0 GHz, achieving EMI values of approximately 18 and 19.5 dB for gypsum and cement boards, respectively, meeting the entry-level value required for commercial applications.

The influence and importance of research and development (R&D) for business sustainability have gained increasing interests, especially in the high-tech sector. However, the efforts of R&D might cause complex and mixed impacts on the financial results considering the associated expenses. Thus, this study aims to examine how R&D efforts may influence business to improve its financial performance considering the dual objectives: the gross and the net profitability. This research integrated a rough-set-based soft computing technique and multiple criteria decision-making (MCDM) methods to explore this complex and yet valuable issue. A group of public listed companies from Taiwan, all in the semiconductor sector, was analyzed as a case study. Initially, more than 30 variables were considered, and the adopted soft computing technique retrieved 14 core attributes—for the dual profitability objectives—to form the evaluation model. The importance of R&D for pursuing superior financial prospects is confirmed, and the empirical case demonstrates how to guide an individual company to plan for improvements to achieve its long-term sustainability by this hybrid approach.

We investigate some information properties of consecutive k-out-of-n:G systems in light of fractional generalized cumulative residual entropy. We firstly derive a formula to compute fractional generalized cumulative residual entropy related to the system's lifetime and explore its preservation properties in terms of established stochastic orders. Additionally, we obtain useful bounds. To aid practical applications, we propose two non parametric estimators for the fractional generalized cumulative residual entropy in these systems. The efficiency and performance of these estimators are illustrated using simulated and real datasets.

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz need to provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT) and fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide POUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm POUT. The calibrated HD2 level is -82.2 dBc at 9.93 dBm POUT, resulting in a transmitter figure of merit (TX_FoM) of -97.52 dB. Higher order harmonic levels remain below -41.2 dBm even at 12.1 dBm POUT, meeting regulatory requirements.

This study describes the development of an automated bag valve mask (BVM) compression system, which, during acute shortages and supply chain disruptions can serve as a temporary emergency ventilator. The resuscitation system is based on the Arduino controller with a real-time operating system installed on a largely RepRap 3-D printable parametric component-based structure. The cost of the system is under $170, which makes it affordable for replication by makers around the world. The device provides a controlled breathing mode with tidal volumes from 100 to 800 milliliters, breathing rates from 5 to 40 breaths/minute, and inspiratory-to-expiratory ratio from 1:1 to 1:4. The system is designed for reliability and scalability of measurement circuits through the use of the serial peripheral interface and has the ability to connect additional hardware due to the object-oriented algorithmic approach. Experimental results demonstrate repeatability and accuracy exceeding human capabilities in BVM-based manual ventilation. Future work is necessary to further develop and test the system to make it acceptable for deployment outside of emergencies in clinical environments, however, the nature of the design is such that desired features are relatively easy to add with the test using protocols and parametric design files provided.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

A typical halogen-free flame-retardant (HFFR) formulation for electric cables may contain polymers, various additives, and fire-retardant fillers. In this study, composites are prepared by mixing natural magnesium hydroxide (n-MDH) with linear low-density polyethylene (LLDPE) and a few types of ethylene-octene copolymers (C₈-POE). Depending on the content of LLDPE and C₈-POE, we obtained composites with different crystallinity that affected the final mechanical properties. The nucleation effect of the n-MDH and the variations in crystallinity caused by the blending of C₈-POE/LLDPE/n-MDH were investigated. In the C₈-POE/LLDPE blend, we found a decrease in the crystallization temperature of LLPDE compared to pure LLDPE and an increase in the crystallization temperature of C₈-POE compared to pure C₈-POE. On the contrary, the addition of n-MDH led to an increase in the crystallization temperature of LLDPE. As expected, the increase in the crystallinity of the polyolefin matrix of composites led to higher elastic modulus, higher tensile strength, and lower elongation at break. Overall, these results show how to obtain the required mechanical features for halogen-free flame-retardant compounds for electric cable applications depending on the quantities of the two miscible components in the final blend.

Glycosylation, a prevalent post-translational modification, plays a pivotal role in regulating intricate cellular processes by covalently attaching glycans to macromolecules. Dysregulated glycosylation is linked to a spectrum of diseases, encompassing cancer, neurodegenerative disorders, congenital disorders, infections, and inflammation. This review delves into the intricate interplay between glycosylation and protein conformation, with a specific focus on the profound impact of N-glycans on the selection of distinct protein conformations, characterized by distinct interactomes – namely protein assemblies - under normal and pathological conditions across various diseases. We begin by examining the spike protein of the SARS virus, illustrating how N-glycans regulate the infectivity of pathogenic agents. Subsequently, we utilize the prion protein and the chaperone glucose-regulated protein 94 as examples, exploring instances where N-glycosylation transforms physiological protein structures into disease-associated forms. Unraveling these connections provides valuable insights into potential therapeutic avenues and a deeper comprehension of the molecular intricacies that underlie disease conditions. This exploration of glycosylation's influence on protein conformation effectively bridges the gap between the glycome and disease, offering a comprehensive perspective on the therapeutic implications of targeting conformational mutants and their pathologic assemblies in various diseases. The goal is to unravel the nuances of these post-translational modifications, shedding light on how they contribute to the intricate interplay between protein conformation, assembly and disease.

This paper explores the Wilsonian renormalization group of probe-D-branes, focusing on the Dirac-Born-Infeld (DBI) action. The analysis involves deriving the constant of motion and formulating the Wilsonian renormalization group equation. The study extends to the infrared regime, considering both zero and non-zero temperatures. Additionally, thermodynamic aspects related to the functional form of the grand potential are discussed. The investigation provides insights into the renormalization of probe-D-branes and their thermodynamic properties.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.

In this work, several random Boolean networks (RBN) are generated and analyzed from two characteristics: their time evolution diagram and their transition diagram. To do this, its randomness is estimated using three metrics, of which algorithmic complexity is the only one capable of revealing both transitions towards the chaotic regime and the algorithmic contribution of certain states to the transition diagram and their relationship with the order they occupy in the temporal evolution of the respective RBN.

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (K_d), can be considered as one of the most important characteristics for any antibody-antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC₅₀ approaches the K_d value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to K_d. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols.

The use of chimeric antigen receptors (CAR-T cells) for the treatment of patients with malignant haematological diseases has become a well-established application, for conditions such as refractory or relapsed B cell acute lymphoblastic leukaemia (B-ALL), B cell lymphomas (BCL), and multiple myeloma (MM). Nearly 35,000 patients have received autologous CAR-T cells for the treatment of these conditions only in the USA. Since their approval by the Food and Drug Administration (FDA) in 2017, over 1200 clinical trials have been initiated globally and there are at least 10 different CAR-T cells with approval by different regulatory agencies around the globe. In the USA the Food and Drug Administration (FDA) has approved 6 commercial CAR-T cells that are widely distributed worldwide. At the time of this writing, several clinical trials have been performed in patients with solid tumours such as glioblastoma, renal and pancreatic cancer, as well as in patients with autoimmune conditions such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SS). There are also several studies showing the potential benefit of CAR-T cells for other non-malignant diseases such as asthma and even fungal infections. In this review, without pretending to cover all the current areas of treatments with CAR-T cells, we offer a brief summary of some of the most relevant aspects of the use of CAR-T cells for some of these conditions.