GPT-4 was released in March 2023 to wide acclaim, marking a very substantial improvement across the board over GPT-3.5 (OpenAI's previously best model, which had powered the initial release of ChatGPT). Despite the genuinely impressive improvement, however, there are good reasons to be highly skeptical of GPT-4's ability to reason. This position paper discusses the nature of reasoning; criticizes the current formulation of reasoning problems in the NLP community and the way in which the reasoning performance of LLMs is currently evaluated; introduces a collection of 21 diverse reasoning problems; and performs a detailed qualitative analysis of GPT-4's performance on these problems. Based on the results of this analysis, the paper argues that, despite the occasional flashes of analytical brilliance, GPT-4 at present is utterly incapable of reasoning.

Exploring the biological significance of mutations in SARS-CoV-2 coronavirus, causing the COVID–19 pandemic, has recently become an area of paramount interest for many researchers, who are pouring their tremendous efforts, in cracking the COVID–19 pandemic code. One of many such mutations that have occurred in the viral genome is V483A mutation, which is a part of the receptor-binding motif (RBM), present in the S1 domain of the spike protein. V483A mutant virus is becoming popular in North America with 36 cases so far, due to its frequent occurrences in recent days. In this review, we have assembled all information, currently available on V483A mutation, and have made a critical analysis based on the perspectives of many researchers all around the world. Comparison is made between the wild type and the V483A mutants to analyze certain factors like the type of interaction between the virus and host cell interface, binding affinity, stability, partition energy, hydrophobicity, occurrence rate, and transmissibility. Insilico dynamic analysis shows minimal alteration in the receptor-binding domain (RBD) of V483A mutant protein in free-state and no significant change of mutant tertiary structure of RBM upon binding to the ACE2 receptor. Comprehensive details about infectivity and evasion of the immune system by the virus are discussed. This information can in turn be of monumental importance in the field of vaccine and drug development because the mutants are becoming resistant to the vaccines and monoclonal antibodies.

As the echoes of ChatGPT's remarkable success continue to permeate the AI community, its formidable successor, GPT-4, has emerged, showing off a wealth of novel features. In this concise paper, we elucidate the capabilities of GPT-4 and conduct a comparative analysis with its predecessor, ChatGPT, offering insights into their relative strengths and advancements in the rapidly evolving field of generative AI. We also present a comprehensive summary of the major performance results reported by OpenAI on GPT-4 across various Natural Language Processing (NLP) tasks. We place great emphasis on the innovative advancements offered by GPT-4 in comparison to its predecessors. Our focus is on highlighting its remarkable performance while also mentioning its limitations. The purpose of this paper is to deliver a succinct understanding of the new features and performance benchmarks of GPT-4.

COVID-19 (2019-nCoV) is a pandemic disease with an estimated mortality rate of 3.4% (estimated by the WHO as of March 3, 2020). Until now there is no antiviral drug and vaccine for COVID-19. The current overwhelming situation by COVID-19 patients in hospitals is likely to increase in the next few months. About 15 percent of patients with serious disease in COVID-19 require immediate health services. Rather than waiting for new anti-viral drugs or vaccines that take a few months to years to develop and test, several researchers and public health agencies are attempting to repurpose medicines that are already approved for another similar disease and have proved to be fairly effective. This study aims to identify FDA approved drugs that can be used for drug repurposing and identify biomarkers among high- risk and asymptomatic groups. In this study gene-disease association related to COVID-19 reported mild, severe symptoms and clinical outcomes were determined. The high-risk group was studied related to SARS-CoV-2 viral entry and life cycle by using Disgenet and compared with curated COVID-19 gene data sets from the CTD database. The overlapped gene sets were enriched and the selected genes were constructed for protein-protein interaction networks. Through interactome, key genes were identified for COVID-19 and also for high risk and asymptomatic groups. The key hub genes involved in COVID-19 were VEGFA, TNF, IL-6, CXCL8, IL10, CCL2, IL1B, TLR4, ICAM1, MMP9. The identified key genes were used for drug-gene interaction for drug repurposing. The chloroquine, lenalidomide, pentoxifylline, thalidome, sorafenib, pacitaxel, rapamycin, cortisol, statins were proposed to be probable drug repurposing candidates for the treatment of COVID-19. However, these predicted drug candidates need to be validated through randomized clinical trials. Also, a key gene involved in high risk and the asymptomatic group were identified, which can be used as probable biomarkers for early identification.

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.

The rapidly increasing adoption of high-resolution accurate-mass methods in analytical laboratories has fueled demand for instruments that combine high performance and reliability with small size and greater ease-of-use. This paper presents the major design principles that are driving the evolution of the hybrid quadrupole-Orbitrap instrument architecture to enable a greater range of applications and users. These principles may be summarized as follows: better usage of physical space and better access for service by means of size reduction of pumping and ion optics; expanded use of technologies from electronics in ion-optical design; flexibility in performance via modularity of design of the hardware and software components; and, harmonization of interfaces with other instruments to facilitate sharing and transferability of analytical workflows. The design of a novel family of hybrid mass spectrometers is described in detail, and performance evaluation is carried out on a wide variety of samples for its three representatives: the Orbitrap Exploris 120, Orbitrap Exploris 240 and Orbitrap Exploris 480 mass spectrometers.The new instrument family is shown to offer compelling potential not only for high-end proteomics and biopharmaceutical applications, but also for screening, trace, targeted and clinical analysis by liquid chromatography/mass spectrometry methods.

Origins of the time, mass, electric charges and magnetic monopoles are explained. The energies, electric charges and magnetic charges of the particles are defined as E = cDtDV and |q| = cDt = E/DV, and |q_m| = c²Dt, respectively, for the 3-D quantized spaces warped along the time axis direction of ct in the 4-D Euclidean space. The energy (or mass) and charges (or electric charges and magnetic charges) are the vectors along the time axis of ct in the 4-D Euclidean space. This new concept is closely connected to the wave function of the quantum mechanics. The electric charges, magnetic charges and energies have the property of the space direction independence. Magnetic monopoles (charges) are the force carrying bosons with the inside electric field time loop. Electric monopoles are the elementary fermions. Photon space fluctuations are explained with the quantized magnetic charges.

Large population passages of the SARS-CoV-2 in the past two and a half years have allowed the circulating virus to accumulate an increasing number of mutations in its genome. The most recently emerging Omicron subvariants have the highest number of mutations in the Spike (S) protein gene and these mutations mainly occur in the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the S gene. The eCDC and the WHO recommend partial Sanger sequencing of the SARS-CoV-2 S gene RBD and NTD on the PCR-positive samples in diagnostic laboratories as a practical means of determining the variants of concern to monitor a possible increased transmissibility, increased virulence, or reduced effectiveness of vaccines against them. The author’s diagnostic laboratory has implemented the eCDC/WHO recommendation by sequencing a 398-base segment of the N gene for the definitive detection of SARS-CoV-2 in clinical samples, and sequencing a 445-base segment of the RBD and a 490-509-base segment of the NTD for variant determination. This paper presents 5 selective cases to illustrate the challenges of using Sanger sequencing to diagnose Omicron subvariant when the samples harbor a high level of co-existing minor subvariant sequences with multi-allelic single nucleotide polymorphisms (SNPs) or possible recombinant Omicron subvariants containing a BA.1 NTD and a BA.2 RBD, which can only be detected by using specially designed PCR primers. The current large-scale surveillance programs using next-generation sequencing (NGS) do not face similar problems because NGS focuses on deriving consensus sequence.

With the existence of several programming languages such as C/C++, Java, C#, LISP, Prolog, Python, Simula, F#, Go, Haskell, Scala, Ruby, Dart, Swift, Groovy etc. and diverse paradigms like structured, object-oriented, list, aspect-oriented, service-oriented, web, mobile and logic programming, there is a need to perform an exhaustive comparative analysis of diverse compilers and environments before making a choice of implementation technology in software engineering. Optimization of compilers helps to reduce execution time by making use of high speed processor registers, thereby, eliminating redundant computation. This paper reports some series of performance analysis done with some popular programming languages including Java, C++, Python and PHP. Programs involving recursive and iterative functions like factorial of large numbers and binary search of large arrays were run on the various platforms with the execution time recorded in milliseconds and represented in a chart. This can aid in making a selection of the appropriate language to use for a given application domain.

Biological systems are highly regulated. They are also highly resistant to sudden perturbations enabling them to maintain the dynamic equilibrium essential for sustenance of life. This robustness is conferred by regulatory mechanisms that influence the activity of enzymes/proteins within their cellular context, to adapt to changing environmental conditions. However, the initial rules governing the study of enzyme kinetics were tested and implemented for mostly cytosolic enzyme systems that were easy to isolate and/or recombinantly express. Moreover, these enzymes lacked complex regulatory modalities. Now, with academic labs and pharmaceutical companies turning their attention to more complex systems (for instance, multi-protein complexes, oligomeric assemblies, membrane proteins and post-translationally modified proteins), the initial axioms defined by Michaelis-Menten (MM) kinetics are rendered inadequate and the development of a new kind of kinetic analysis to study these systems is required. The current review strives to present an overview of enzyme kinetic mechanisms that are atypical and, oftentimes, do not conform to the classical MM kinetics. Further, it presents initial ideas on the design and analysis of experiments in early drug-discovery for such systems, to enable effective screening and characterisation of small-molecule inhibitors with desirable physiological outcomes.

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.

Abstract The COVID-19 pandemic is thought to began in Wuhan, China in December 2019. Mobility analysis identified East-Asia and Oceania countries to be highly-exposed to COVID-19 spread, consistent with the earliest spread occurring in these regions. However, here we show that while a strong positive correlation between case-numbers and exposure level could be seen early-on as expected, at later times the infection-level is found to be negatively correlated with exposure-level. Moreover, the infection level is positively correlated with the population size, which is puzzling since it has not reached the level necessary for population-size to affect infection-level through herd immunity. These issues are resolved if a low-virulence Corona-strain (LVS) began spreading earlier in China outside of Wuhan, and later globally, providing immunity from the later appearing high-virulence strain (HVS). Following its spread into Wuhan, cumulative mutations gave rise to the emergence of an HVS, known as SARS-CoV-2, starting the COVID-19 pandemic. We model the co-infection by an LVS and an HVS, and show that it can explain the evolution of the COVID-19 pandemic and the non-trivial dependence on the exposure level to China and the population-size in each country. We find that the LVS began its spread a few months before the onset of the HVS, and that its spread doubling-time is $\sim 1.59\pm 0.17$ times slower than the HVS. Although more slowly spreading, its earlier onset allowed the LVS to spread globally before the emergence of the HVS. In particular, in countries exposed earlier to the LVS and/or having smaller population-size, the LVS could achieve herd-immunity earlier, and quench the later-spread HVS at earlier stages. We find our two-parameter (the spread-rate and the initial onset time of the LVS) can accurately explain the current infection levels (R^2$\mathrm{=0.74}$; correlation p-value (p) of 5x10^-13$$). Furthermore, countries exposed early should have already achieved herd-immunity. We predict that in those countries cumulative infection levels could rise by no more than 2-3 times the current level through local-outbreaks, even in the absence of any containment measures. We suggest several tests and predictions to further verify the double-strain co-infection model and discuss the implications of identifying the LVS.

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.

The use of machine learning techniques in predictive health care is on the rise with minimal data used for training machine-learning models to derive high accuracy predictions. In this paper, we propose such a system, which utilizes Heart Rate Variability (HRV) as features for training machine learning models. This paper further benchmarks the usefulness of HRV as features calculated from basic heart-rate data using a window shifting method. The benchmarking has been conducted using different machine-learning classifiers such as artificial neural network, decision tree, k-nearest neighbour and naive bays classifier. Empirical results using MIT-BIH Arrhythmia database shows that the proposed system can be used for highly efficient predictability of abnormality in heartbeat data series.

The high radio frequency polarization imaging of non-thermal emission from active galactic nuclei (AGN) is a direct way to probe the magnetic field strength and structure in the immediate vicinity of supermassive black holes (SMBHs) and is crucial in testing the jet-launching scenario. To explore the the magnetic field configuration at the base of jets in blazars, we took advantage of the full polarization capabilities of the GMVA (Global Millimeter VLBI Array). With an angular resolution of ~50 micro-arcseconds at 86 GHz, one could reach scales down to ~900 Schwarzschild radii (for a 10^9 solar mass black hole). We present here the preliminary results of our study on the blazar BL Lac. Our results imply that on sub-mas scales the core and central jet of BL Lac is significantly polarized with two distinct regions of polarized intensity. We also noted a great morphological similarity between the 7mm/3mm VLBI images at very similar angular resolution.

In this paper, we first discuss the research status and application progress of the finite element method and the smoothed particle method. By analyzing the advantages of the smoothed particle method and the finite element method, a new coupling algorithm, namely FEM-SPH algorithm, is proposed. By the method of comparison, it shows that finite element method and SPH method in the simulation of large deformation problems each have advantages and disadvantages, the finite element method smoothed particle coupling algorithm is effective to achieve the performance of high computational efficiency and can naturally simulate large deformation problems across. In the process of calculation, the large deformation unit can be freely into an algorithm to facilitate the calculation accuracy and efficiency of three methods of numerical simulation. Through the study found, FEM-SPH algorithm not only overcome the defect of smooth particle tensile instability, but also overcomes the problem of low efficiency of finite element computation. To further test the FEM-SPH algorithm has advantages in the practical engineering, we have carried out the actual test to the example of the super high speed collision, concluded that, since the target of most of the computational domain is always finite element, smoothed particle focused only in contact with the projectile and target of local area, particle number is not much, the whole calculation process just ten minutes, computational efficiency has been greatly improved, at the same time in the simulation of large deformation, the advantage is very obvious .This provides a criterion for the actual project, depending on the specific material deformation mode and choose a more appropriate conversion algorithm.

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.

Originally developed to image the shadow region of the central black hole in Sagittarius A* and in the nearby galaxy M87, the Event Horizon Telescope (EHT) provides deep, very high angular resolution data on other AGN sources too. The challenges of working with EHT data have spurred the development of new image reconstruction algorithms. This work briefly reviews the status of the EHT and its utility for observing AGN sources, with emphasis on novel imaging techniques that offer the promise of better reconstructions at 1.3 mm and other wavelengths.

A high intake of carbohydrates, associated with obesity, is one of the major causes of fatty liver disease in humans. This study investigated how high carbohydrate intake induces fatty liver disease in Blunt snout bream (Megalobrama amblycephala). Blunt snout bream were fed a high-carbohydrate diet (HCBD) for 60 days. Their growth indices were evaluated, and the transcriptomes, metabolites, biochemistry, and histology of their blood and livers were analyzed. The final weight, weight gain, specific growth rate, and feed conversion ratio were all higher in the HCBD group than in the control group, but not significantly so (P > 0.05). The hepatosomatic index (HSI) differed significantly in the two groups (P < 0.05), and the metabolomics results showed that a high carbohydrate intake induced significant increases in plasma α/β-glucose, succinate, and tyrosine, which could increase hepatic glycogen and triglyceride. Low levels of betaine were also found in the livers of the HCBD group. The histology and blood biochemistry results suggested abnormal liver, with excessive lipid accumulation and liver damage. A transcriptome analysis and quantitative reverse transcription–PCR (RT–qPCR) indicated that the expression of the factors INSR, IRS, PI3K, PDK, AKT, ACC, IL6, AP1, ChREBP-MLX, PEPCK, and FBP in the insulin signaling pathway was significantly upregulated and that of SOCS3, GSK3β, and AMPK significantly downregulated in the HCBD. This pattern is associated with the nonalcoholic fatty liver disease (NAFLD) pathway. This study extends our understanding of how high carbohydrate causes increased fat deposition in the liver, enhanced glycolysis (α/β-glucose) in the plasma, and reduced betaine in the liver. This leads to activation of hepatocyte insulin resistance and lipogenesis by regulating the expression of genes related to fatty liver disease.

The preparation of gold nanoparticles (AuNPs) involves a variety of chemical and physical methods. These methods use toxic and environmentally harmful chemicals. Consequently, the synthesis of AuNPs using green chemistry has been under investigation to develop eco-friendly nanoparticles. One method to achieve this is the use of plant-derived phytochemicals capable of reducing gold ions to produce AuNPs. The aim of this study was to implement a facile microtitre-plate method to screen a large number of aqueous plant extracts to determine the optimum concentration (OC) to bio-synthesize the AuNPs. Several AuNPs of different sizes and shapes were successfully synthesized and characterized from seventeen South African plants. The characterization was done using Ultra Violet-Visible Spectroscopy, Dynamic Light Scattering, High Resolution Transmission Electron Microscopy and Energy-Dispersive X-ray Spectroscopy. We also studied the effects of temperature on the synthesis of the nanoparticles and measured its effect on the particle size of the synthesized AuNPs and the data showed that changes in temperatures affect the size and dispersity of the generated AuNPs. Further, some of the synthesized AuNPs were stable upon incubation with different biological solutions in vitro.

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

IL1RA intron 2 86-bp repeat and IL4 intron 3 70-bp repeat are VNTRs that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher adiposity - even after controlling for ethnicity [Odds Ratio (OR) of I/II genotype = 12.21 (CI = 2.54, 58.79; p = 0.002); II allele = 5.78 (CI = 1.73, 19.29; p = 0.004)]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23; p = 0.03)]. TBF was also significantly higher in those with IL1RA II allele compared with I allele (31.79 ± 2.52 vs. 23.51 ± 0.40; p = 0.005). Taken together, IL1RA intron 3 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects.

An experimental study is carried out in a cavitation tunnel on a propeller operating downstream of a non-uniform wake. The goal of this work is to establish quantitative correlations between the near pressure field and the cavitation pattern that takes place on the propeller blades. The pressure field is measured at the walls of the test section and in the near wake of the propeller, and is combined with quantitative high-speed image recording of the cavitation pattern. Through simple harmonic analysis of the pressure data and image processing techniques that allow to retrieve the cavitation extension and volume, we discuss the potential sources that generate the pressure fluctuations. Time correlations are unambiguously established between pressure peak fluctuations and cavitation collapse events, based upon the Rayleigh collapse time. Finally, we design a model to predict the cavitation-induced pressure fluctuations from the derivation of the cavitation volume acceleration. This simple model demonstrates a remarkable agreement with the actual pressure field.

Warming of the climate system is unequivocal, and many of the observed changes are unprecedented over five decades to millennia. Globally the atmosphere and ocean is increasingly getting warmer, the amount of ice on the earth is decreasing over the oceans, and the sea level has risen. According to Intergovernmental Panel on Climate Change, the total increasing temperature globally averaged combined land and surface between the average of the 1850-1900 period and the 2003 to 2012 period is 0.78 °C (0.72 to 0.85). But should we prepare for such the relatively small change? The importance is not the mean of the warming but the considerable likelihood of climate change that could trigger extreme natural hazards. The impact and the risk of climate change associated with railway infrastructure have not been fully addressed in the literature due to the difference in local environmental parameters. On the other hand, the current railway network in Malaysia, over the last decade, has been significantly affected by severe weather conditions such as rainfall, lightning, wind and very high temperatures. Our research findings point out the extremes that can lead to asset system failure, degraded operation and ultimately, delays to train services. During the period of flood, the embankment of the track can be swept away and bridge can be demolished, while during drought, the embankment of the track can suffer from soil desiccation and embankment deterioration, high temperature increases the risk of track buckling and high winds can result in vegetation or foreign object incursion on to the infrastructure as well as additional quasi-static burden exerted. This review is of significant importance for planning and design of the newly proposed high speed rail link between Malaysia and Singapore.

The activity and cyclability of Cu-MOF-74 as catalyst was studied for the ligand-free C-O cross-coupling reaction of 4-nitrobenzaldehyde (NB) with phenol (Ph) to form 4-formyldiphenyl ether (FDE). Cu-MOF-74 is characterized by unsaturated copper sites in a highly porous metal-organic framework. The influence of solvent, reaction temperature, NB/Ph ratio, catalyst concentration and basic agent (type and concentration) were evaluated. High conversions were achieved at 120°C, 5 mol% of catalyst, NB/Ph ratio of 1:2, DMF as solvent and 1 equivalent of K2CO3 base. The activity of Cu-MOF-74 material was higher than other ligand-free copper catalytic systems tested in this study. This catalyst was easily separated and reused in five successive runs, achieving a remarkable performance without significant porous framework degradation. The leaching of copper species in the reaction medium was negligible. The O-arylation between NB and Ph took place only in the presence of Cu-MOF-74 material, being negligible without the solid catalyst.

The present work investigates primarily the morphology evolution of the body-centered-cubic (BCC)/B2 phases in AlxNiCoFeCr high-entropy alloys (HEAs) with increasing Al content, which has been neglected so far. There exist two types of microscopic morphologies of BCC and B2 phases in this HEA series: one is the weave-like morphology induced by the spinodal decomposition, and the other is the microstructure of a spherical disordered BCC precipitation on the ordered B2 matrix that appears in HEAs with a much higher Al content. The shape of coherent precipitates is found to be closely related to the lattice misfit between BCC and B2 phases, which is sensitive to Al. The mechanical properties, including the compressive yielding strength and microhardness of the AlxNiCoFeCr HEAs, are also discussed in light of the concept of the valence electron concentration (VEC).

A high step-up DC-to-DC converter that integrates an isolated transformer and a switched-clamp capacitor is presented in this study. The voltage stress of the main power switch should be clamped to 1/4 V by using the turn ratio and switched-clamp capacitor of an isolated transformer to achieve a high voltage gain. In addition, a passive clamp circuit is employed reduce voltage stress on the main power switch. The energy of the leakage inductor can be recycled by the clamp capacitor because of the passive clamp circuit, thereby improving the power converter efficiency. The converter consists of one isolated transformer, one main switch, three capacitors, and four diodes. Operating principle and steady-state analyses are also discussed. Finally, a 24-V-input voltage to 200-V-output voltage and a 150 W output power prototype converter are fabricated in the laboratory. The maximum efficiency of the converter is 95.1 at 60 W.

Aerial image classification has become popular and has attracted extensive research efforts in recent decades. The main challenge lies in its very high spatial resolution but relatively insufficient spectral information. To this end, spatial-spectral feature extraction is a popular strategy for classification. However, parameter determination for that feature extraction is usually time-consuming and depends excessively on experience. In this paper, an automatic spatial feature extraction approach based on image raster and segmental vector data cross-analysis is proposed for the classification of very high spatial resolution (VHSR) aerial imagery. First, multi-resolution segmentation is used to generate strongly homogeneous image objects and extract corresponding vectors. Then, to automatically explore the region of a ground target, two rules, which are derived from Tobler’s First Law of Geography (TFL) and a topological relationship of vector data, are integrated to constrain the extension of a region around a central object. Third, the shape and size of the extended region are described. A final classification map is achieved through a supervised classifier using shape, size, and spectral features. Experiments on three real aerial images of VHSR (0.1 to 0.32 m) are done to evaluate effectiveness and robustness of the proposed approach. Comparisons to state-of-the-art methods demonstrate the superiority of the proposed method in VHSR image classification.

This study evaluated batch fermentation modes, namely, separate hydrolysis and fermentation (SHF), Quasi-simultaneous saccharification and fermentation (Q-SSF), and simultaneous saccharification and fermentation (SSF), and fermentation conditions, i.e., enzyme and yeast loadings, nutrient supplementation and sterilization, on high titer bioethanol production from SPORL-pretreated Douglas-fir forest residue without detoxification. The result indicated Q-SSF and SSF were obviously superior to SHF operation in terms of ethanol yield. The enzyme loading showed a strong positive correlation between enzyme loading and the ethanol yield. The nutrient supplementation and sterility was not necessary for ethanol production from SPORL-pretreated Douglas-fir. The yeast loading showed no significant influence on the ethanol yield for typical SSF conditions. The terminal ethanol titer of 43.2 g/L, or 75.1% theoretical based on glucose, mannose, and xylose theoretical was achieved when SSF was conducted at the condition of following: whole slurry solids loading of 15%, enzyme loading of 20 FPU/g glucan, 1.8 g/kg (wet) yeast loading, without nutrition supplementation and sterilization, at 38°C, on shake flask at 150 rpm for 96h. It is believed that with mechanical mixing, enzyme loading can be substantially reduced with affect ethanol yield by using a long fermentation time.

Cocrystallizaiton could improve most physicochemical properties of specific active pharmaceutical ingredients, which has great potential in pharmaceutical development. In this study, the cocrystal of nitrofurantoin and 4-aminobenzoic acid was prepared with solid-state (solvent-free or green-chemistry) grinding approach, and the above cocrystal has been characterized by Raman and terahertz vibrational spectroscopic techniques. Spectral results show that the vibrational modes of the cocrystal within the whole spectral region are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman spectra. These results offer us unique means for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic of cocrystal formation within pharmaceutical fields.

One mechanism by which fructose could exert deleterious effect in metabolism and inflammation is via its potency vis-à-vis de Maillard reaction. We employed simulated stomach and duodenum digestion of ovalbumin to test the hypothesis that indeed AGEs are formed by fructose during simulated digestion of an ubiquitous food protein with intrinsic allergenic potential and under model physiological conditions. Methods: OVA was subjected to simulated gastric and intestinal digestion using standard models, in presence of fructose or glucose (0-100 mM). Peptide fractions were analyzed by fluorescence spectroscopy and intensity at Excitation: λ370 nm, Emission: λ 440nm. Results: AGE adducts form between fructose and OVA which can be found in peptide fractions (< 5 kDa) at times (30 min) and concentration ranges (10 mM) plausibly found in the intestines, whereas no reaction occurs with glucose. The reaction is inhibited by chlorogenic acid at concentrations compatible with those found in the gut. The reaction is inhibited by AG, a specific antiglycation agent. Conclusion: Our proof of principle study shows that fructose-AGE formation on an ubiquitous allergenic protein indeed occurs in one hour and thereby may pave the way for the study of yet another mechanism by which the excess fructose in our Western diets is contributing to disease: intestinal AGE formation, absorption and RAGE engagement.

Transition-metal-free synthesis of 4-pyrones via TfOH-promoted nucleophilic addition/cyclization of diynones and water has been developed. This transformation is simple, atom economical and environmentally benign, providing rapid and efficient access to substituted 4-pyrones.

The open source CFD code OpenFOAM has emerged as one of the most popular alternative to commercial CFD solvers. The recent version of OpenFOAM supports overlapping grids, so called Overset mesh. In this type of mesh, one or more sub-collection of control volumes (or cells) are allowed to overlap with other set of cells. This allows for great flexibility in modelling Fluid Structure Interaction (FSI) problems. Fluid mesh can be standard structured mesh of a rectangular/cuboidal/or cylindrical domain. The structure mesh can be generated separately by creating multiple layers around a given body. The overset mesh functionality allows for overlapping or immersing this structured mesh inside the fluid mesh and a relevant FSI or moving dynamics problems can be solved. The idea of overset mesh has been around since eighties but its support in OpenFOAM is very recent. Most CFD codes which support overset mesh have either been in-house or commercial CFD codes. OpenFOAM's support for overset is the first major open source code resource available for CFD problems. The aim of this research is to solve a classical benchmark airfoil problem using OpenFOAM overset mesh and compare the numerical results with experimental result. We report here flow simulations results around NACA 0018. The result obtained from overset mesh compares convincingly well with experimental results. Computations have been carried out for Reynolds numbers in the range of 10⁵ with angle of attack ranging from α= 5 degree to α= 30 degree with an interval of 5 degree. Turbulence is incorporated using k - ε turbulence model. This study helps developing confidence in using OpenFOAM overset support for more complicated flows and moving dynamics. This report is complemented with a brief description of finite volume discretization using overset mesh.

Background: Studies employing next-generation sequencing (NGS) show that the oral fungal community (mycobiome) is far more complex than hitherto thought. However, the role of the oral mycobiome in health and disease, including oral carcinogenesis, has not been explored. Objective: To characterize the mycobiome associated with oral squamous cell carcinoma (OSCC). Methods: Tissue biopsies [cases: 25 OSCC; controls: 27 intra-oral fibro-epithelial polyp (FEP)] were collected from oral and maxillofacial units in Sri Lanka. Total DNA was extracted and subjected to sequencing of the fungal ITS2 region using Illumina’s 2x300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a BLASTN-algorithm with UNITE’s named species sequences as reference. Downstream analyses were performed using QIIME and LEfSe. Results: 364 species representing 160 genera and 2 phyla (Ascomycota and Basidiomycota) were identified, with Candida and Malassezia making up 48% and 11% of the average mycobiome, respectively. However, only 5 species and 4 genera were detected in ≥50% of the samples. The species richness and diversity were significantly lower in OSCC. At the genus level, Candida, Hannaella and Gibberella were overrepresented in OSCC while Alternaria and Trametes were more abundant in FEP. Species-wise, C. albicans, C. etchellsii and Hannaella luteola-like species were enriched in OSCC while Malassezia restricta, Aspergillus tamarii, Alternaria alternate, Cladosporium halotolerans, and Hanseniaspora uvarum-like species were the most significantly abundant in FEP. Conclusions: A dysbiotic mycobiome dominated by C. albicans was found in association with OSCC. Whether this dysbiosis plays a role in oral carcinogenesis warrants further investigation.

Studies on the possible association between bacteria and oral squamous cell carcinoma (OSCC) remain inconclusive, largely due to methodological variations/limitations. The objective of this study was to characterize the species composition as well as functional attributes of the bacteriome associated with OSCC. DNA obtained from 20 fresh OSCC biopsies (cases) and 20 deep-epithelium swabs (matched control subjects) were sequenced for the V1-V3 region using Illumina’s 2x300 bp chemistry. High quality, non-chimeric merged reads were classified to species level using a prioritized BLASTN-algorithm. Downstream analyses were performed using QIIME, PICRUSt, and LEfSe. Fusobacterium nucleatum subsp. polymorphum was the most significantly overrepresented species in the tumors followed by Pseudomonas aeruginosa and Campylobacter sp. Oral taxon 44, while Streptococcus mitis, Rothia mucilaginosa and Haemophilus parainfluenzae were the most significantly abundant in the controls. Functionally, genes involved in bacterial mobility, flagellar assembly, bacterial chemotaxis and LPS synthesis were enriched in the tumors while those responsible for DNA repair and combination, purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, ribosome biogenesis and glycolysis/gluconeogenesis were significantly associated with the controls. This is the first epidemiological evidence for association of F. nucleatum and P. aeruginosa with OSCC. Functionally, an “inflammatory bacteriome” is enriched in OSSC.

In this paper we introduce a computational model for the simulation of hypervelocity impact (HVI) phenomena which is based on the Discrete Element Method (DEM). Our paper constitutes the first application of DEM to the modeling and simulating of impact events for velocities beyond 5 kms⁻¹. We present here the results of a systematic numerical study on HVI of solids. For modeling the solids, we use discrete spherical particles that interact with each other via potentials. In our numerical investigations we are particularly interested in the dynamics of material fragmentation upon impact. We model a typical HVI experiment configuration where a sphere strikes a thin plate and investigate the properties of the resulting debris cloud. We provide a quantitative computational analysis of the resulting debris cloud caused by impact and a comprehensive parameter study by varying key parameters of our model. We compare our findings from the simulations with recent HVI experiments performed at our institute. Our findings are that the DEM method leads to very stable, energy–conserving simulations of HVI scenarios that map the experimental setup where a sphere strikes a thin plate at hypervelocity speed. Our chosen interaction model works particularly well in the velocity range where the local stresses caused by impact shock waves markedly exceed the ultimate material strength.

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

In the case of long-stator linear drive, unlike rotative drives for which speed or position sensors are a single unit attached to the shaft, these sensors extend along the guideway. The position signals transmitted from maglev vehicle can’t meet the need of the real-time propulsion control in the on-ground inverter power substations. In this paper the design of the propulsion inverter control system with a position estimator for driving long-stator synchronous motor in high speed maglev train is proposed. The experiments have been carried out at the 150m long guideway in O-song test track. To investigate the performance of the position estimator, the propulsion control system with and without the position estimator are compared. The result confirms that the proposed strategy can meet the dynamic property need of propulsion inverter control system for driving long-stator linear synchronous motors

High pressure crystallization technique has been successfully used to prepare an elusive form II of a non-steroidal anti-inflammatory drug, Mefenamic acid. Single crystal of form II was grown at 0.3 GPa from an 4:1 methanol/ ethanol mixture as a solvent using Diamond Anvil Cell. Comparison of crystal structures show that the efficient packing of MA molecules in Form II results from the structural flexibility of MA acid molecules. Compression studies performed on the single crystal of form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallization at high pressure results.

Semantic image segmentation has recently witnessed considerable progress by training deep convolutional neural networks (CNNs). The core issue of this technique is the limited capacity of CNNs to depict visual objects. Existing approaches tend to utilize approximate inference in a discrete domain or additional aides and do not have a global optimum guarantee. We propose the use of the multi-label manifold ranking (MR) method in solving the linear objective energy function in a continuous domain to delineate visual objects and solve these problems. We present a novel embedded single stream optimization method based on the manifold ranking (MR) model to avoid approximations without sacrificing expressive power. In addition, we propose a novel network, which we refer to as dual multi-scale manifold ranking (\textbf{DMSMR}) network, that combines the dilated, multi-scale strategies with the single stream MR optimization method in the deep learning architecture to further improve the performance. Experiments on high resolution images, including close-range and remote sensing datasets, demonstrate that the proposed approach can achieve competitive accuracy without additional aides in an end-to-end manner.

A series of novel N-n-butyl-1,8-naphthalimide derivatives were synthesized via a three-step reaction involving nucleophilic substitution and acylation. All of the compounds were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis, and the crystal structure of N-n-butyl-4-[N’,N’-bis(2`,4`-dichlorobenzoyl)ethylamino]-1,8-naphthalimide was determined. The π-π stacking interactions and hydrogen bonds between the two molecular core planes (naphthalimide ring) and the van der Waals forces between the flexible n-butyl groups resulted in a 3D long-chain structure. The UV-vis and fluorescence properties of the title compounds were investigated. The results indicated that the monosubstituted 1,8-naphthalimide derivatives bearing an electron-donating group on the benzene ring or a structure with a larger conjugative effect exhibited enhanced fluorescence properties.

Abstract: High step-up voltage gain nonisolated DC-DC converter have attracted much attention in photovoltaic, fuel cells and other renewable energy system applications. In this paper, by combining input current ripple-free boost cell with coupled-inductor voltage-doubler cell, an input current ripple-free high voltage gain nonisolated converter is proposed. In addition, passive lossless clamp circuit is adopted to recycle the leakage inductor energy and to reduce the voltage spike across the power switch. By utilizing voltage-doubler cell consisting of diode and capacitor, the voltage stress of switch is further reduced and the resonance between the leakage inductor and the stray capacitor of the output diode is eliminated. A low switch-on-resistance low-voltage-rated MOSFET can therefore be employed to reduce the conduction loss and cost. The reverse recovery loss of output diode is reduced, and the efficiency of converter can be improved. Furthermore, the proposed converter can achieve nearly zero input current-ripple and make the design of electromagnetic interference (EMI) filter easy. Steady state analysis and operation mode of the converter is performed. Finally, experimental results are presented to verify the analysis results of the proposed converter.

The abundant mechanical vibration energy in bridge road environment can be converted into electric energy by using the piezoelectric energy harvest technology, which could be an efficient way to provide energy required by the wireless sensor network in the bridge condition monitoring system. An autonomous energy harvesting system has been designed based on cantilever beams for sensing and acquiring the bridge vibration energy. After the analysis of the dynamic properties of the piezoelectric cantilever beam in the energy conversion, three kinds of interface circuits were compared through simulation and experimental results. It was shown that the VD interface circuit has less power loss. Furthermore, the proposed closed loop control method based on the VD circuit was simple, adaptive, and self-powered, which is suitable for the road energy harvesting application. Finally, the energy harvesting system based on VD circuit was realized with harvested power of around 0.8mW.

The oxidative stress is one of the main cause for cardiovascular diseases (like Hypertension) also one of the results of these diseases. This study involved 56 subjects matched ages and sex divided into two groups; 28 hypertensive subject and 28 healthy subject as control group. The following analysis was done: 4-Hydroxy-2-nonenal(4HNE) and albumin. The results show that there is a significant increase in (4HNE) between patients group and control group. The increase in 4HNE which is a product of lipid peroxidation is attributed to destruction in body cell caused by due to the increase in stress events. It has been concluded that is important nappy on ideal weight, because obesity considered main factors for heart disease and hardening of the arteries. The aim of this study was to investigate the relationship between of some oxidative stress markers and cardiovascular diseases.

The critical hypoxia in COVID-19 patients during this pandemic, has taken away many lives all around the globe. The mechanism has been poorly understood and initially, word got around that it was a SARS (Severe Acute Respiratory Syndrome) pneumonia. The atypical images in lung computerized axial tomography (CAT) scans were alarming. This immediately alerted everyone including poor countries to purchase lacking sophisticated ventilator equipment. However, in some countries, even 88% of the patients on ventilators lost their lives. New observations and pathological findings are gradually clarifying the disease. What seems evident is that it is not only one disease but several, with different responses in different countries and different altitudes. The critical hypoxia and «gasping» present in some patients are not totally understood. It was mentioned that it could be like a High-Altitude Pulmonary Edema (HAPE). Hereby, as high-altitude medicine and hypoxia physiology specialists, we compare the pathophysiology with that of high-altitude exposure in order to understand the mechanisms involved. Some differences in lung radiological images along with transmission and viral attack mechanisms are discussed. The oxygen transport triad used at high-altitude can be applied on this pathology in order to propose even the use of erythropoietin (EPO) early in the treatment. The immune system is the most important long-term survival tool, so we suggest a short-term strategy: the use of special Earth open-circuit astronaut-resembling suits with effective outside air filtering re-breathing mechanisms in order to return to work and daily activities, without contamination risk. Thereby, the curve can be flattened without quarantine and the economy could recover.

The objective of this study is to evaluate the effect of constitutive equations on the prediction accuracy for springback in cold stamping with various deformation modes. In this study, two types of yield functions—Hill’48 and Yld2000-2d—were considered to describe yield behavior. Isotropic and kinematic hardening models based on the Yoshida–Uemori model were also adopted to describe hardening behavior. Various material tests (such as uniaxial tension, tension- compression, loading-unloading, and hydraulic bulging tests) were carried out to determine the material parameters of the models. The obtained parameters were implemented in the finite element (FE) simulation to predict springback, and the results were compared with experimental data. U-bending and T-shape drawing were employed to evaluate the springback prediction accuracy. Obviously, the springback prediction accuracy was greatly influenced by constitutive equations. Therefore, it is important to choose appropriate constitutive equations for accurate description of material behaviors in FE simulation.

This study describes all the properties of high T_c cuprates by introducing rotating holes that are created by angular momentum conservations on a 2D CuO₂ surface, and which have a different mass from that of a normal hole because of the magnetic field energy induced by the rotation. This new particle called a macroscopic Boson describes the doping dependences of pseudo-gap temperature and the transition temperature at which an anomaly metal phase appears and describes the origin of the pseudo-gap. Furthermore, this study introduces a new model to handle many-body interactions, which results in a new statistic equation. This statistic equation describing many-body interactions accurately explains why high T_c cuprates have significantly high critical temperatures. Moreover a partition function of macroscopic Bosons describes all the properties of anomaly metal phase, which sufficiently agree with experiments, using the result from our previous study [1] that analytically describes the doping dependence of T_c. By introducing a macroscopic Boson and the new statistical model for many-body interactions, this study uncovered the mystery of high T_c cuprates, which have been a challenge for many researchers. An important point is that, in this study, pure analytical calculations are consistently conducted, which agree with experimental data well (i.e., they do not use numerical calculations or fitting methods but use many actual physical constants).

In the end of December 2019, a new strain of coronavirus was identified in the Wuhan city of Hubei province in China. Within a shorter period of time, an unprecedented outbreak of this strain was witnessed over the entire Wuhan city. This novel coronavirus strain was later officially renamed as COVID-19 (Coronavirus disease 2019) by the World Health Organization. The mode of transmission had been found to be human-to-human contact and hence resulted in a rapid surge across the globe where more than 1,100,000 people have been infected with COVID-19. In the current scenario, finding potent drug candidates for the treatment of COVID-19 has emerged as the most challenging task for clinicians and researchers worldwide. Identification of new drugs and vaccine development may take from a few months to years based on the clinical trial processes. To overcome the several limitations involved in identifying and bringing out potent drug candidates for treating COVID-19, in the present study attempts were made to screen the FDA approved drugs using High Throughput Virtual Screening (HTVS). The COVID-19 main protease (COVID-19 Mpro) was chosen as the drug target for which the FDA approved drugs were initially screened with HTVS. The drug candidates that exhibited favorable docking score, energy and emodel calculations were further taken for performing Induced Fit Docking (IFD) using Schrodinger’s GLIDE. From the flexible docking results, the following four FDA approved drugs Sincalide, Pentagastrin, Ritonavir and Phytonadione were identified. In particular, Sincalide and Pentagastrin can be considered potential key players for the treatment of COVID-19 disease.

The article reveals distinctive features of the interaction between architectural and structural solutions for the design of tall buildings as well as spotlights the most distinctive cases of expression. In the contemporary world, interaction is turning into the antithesis of the formerly dominant utilitarian attitude and standardization of tall buildings architectural solutions. Meanwhile, the search for rational structural solutions leads to new possibilities of architectural expression. This necessitates the transformation of a structural solution and its adaptation to the need of a modern architect to be exceptional and noticed. Interaction covers the current as well as retrospective and perspective periods. SWOT analysis was used by the authors of the article to assess the interaction between architectural and structural solutions in tall buildings design, select the most important criteria that could be used searching for rational architectural and structural solutions in future by applying multi-criteria decision making methods.

Previous studies on the prognostic impact of survivin expression in gastrointestinal (GI) cancer have yielded inconsistent results. This study was initiated to assess the relationship between survivin expression and overall survival (OS) or disease free survival (DFS) in GI cancer patients. We applied system literature searches on EMBASE, PubMed, Web of science, and the Cochrane library to conduct this up-to-date meta-analysis. Thirty studies with totally 3622 GI cancer patients were collected. The prevalence of high survivin expression in GI cancer was 0.57 (95% CI: 0.51-0.63). High survivin expression was significantly associated with shorter OS (HR 1.57, 95% CI: 1.42-1.74) and DFS (HR 1.38, 95% CI: 1.21-1.58). Subgroup analysis also showed significant association between high survivin expression and poorer OS or DFS in gastric cancer or colorectal cancer. In summary, our study indicated that high survivin expression was related to poor prognosis in GI cancer. Well-designed studies with large sample and more convincing data are needed to confirm our conclusion.

Tarsal tunnel syndrome is a focal compressive neuropathy of the posterior tibial nerve or one of its associated branches. Brief mention is made in the literature of the use of corticosteroid injections for this condition. The basic technique of hydrodissection is used for other nerve entrapments and includes identifying the region of nerve compression, and the injection of a fluid medium to dissect between structures or fascial planes. We introduce our treatment protocol using a methylprednisolone/sterile water/ropivacaine hydrochloride injectate mix and peripheral nerve stimulation to a perform hydrodissection technique for tarsal tunnel syndrome.

In networked driving simulation, two or more human drivers participate interactively within a shared virtual environment. Thereby, typical applications of driving simulation can be extended to consider multi-driver scenarios, where a much closer approximation of reality with its unpredictability is achieved. However, the utilized network is typically prone to a considerable amount of message traffic. In addition to restricted system scalability, the resulting degradation of network performance leads to invalid simulation outcomes or unacceptable system behavior. High-level architecture (HLA) is an IEEE standard for networked simulation. Data distribution management (DDM) is one of the service groups provided by HLA standard. The aim of the DDM service is to reduce network traffic and to save effort required to process unnecessary received data. However, different approaches for current DDM implementations show major drawbacks in terms of utilization complexity, inefficiency, and yet added network overhead. This paper presents a concept of an interest manager that takes over the DDM functionality and avoids these drawbacks. Simulation data is exchanged between the participating driving simulators only when it is necessary according to the driving situations. The concept is validated by analyzing the network load of two driving maneuvers with and without the interest manager.

_{Superconducting foams of YBa$_2$Cu$_3$O$_y$ (YBCO) are proposed as trapped field magnets or supermagnets. The foams with an open-porous structure are light-weight, mechanically strong and can be prepared in large sample sizes. The trapped field distributions were measured using a scanning Hall probe on various sides of an YBCO foam sample after field-cooling in a magnetic field of 0.5 T produced by a square Nd-Fe-B permanent magnet. The maximum trapped field (TF) measured is about 400 G (77 K) at the bottom of the sample. Several details of the TF distribution, the current flow and possible applicatons of such superconducting foam samples in space applications, e.g., as active elements in flux-pinning docking interfaces (FPDI) or as portable strong magnets to collect debris in space, are outlined.}

Endoplasmic reticulum (ER) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are up-regulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression, and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation up-regulates SOX2OT expression. This up-regulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ER stress reprogramming of breast cancer cells.

In the recent concrete industry, high fluidity concrete is being widely used for the pouring of dense reinforced concrete. Normally, in the case of high fluidity concrete, it includes high binder contents, so it is necessary to replace part of the cement through admixtures such as fly ash to procure economic feasibility and durability. This study shows the mechanical properties and field applicability of high fluidity concrete that using mass of fly ash as alternative materials of cement. The high fluidity concrete mixed with 50% fly ash was measured to manufacture concrete that applies low water/binder ratio to measure the mechanical characteristics as compressive strength and elastic modulus. Also, in order to evaluate the field applicability, high fluidity concrete containing high volume fly ash was evaluated that fluidity, compressive strength, heat of hydration and drying shrinkage of concrete.

A space charge density wireless measurement system based on the idea of distributed measurement is proposed for collecting and monitoring the space charge density in an ultra-high-voltage direct-current (UHVDC) environment. The proposed system architecture is composed of a number of wireless nodes connected with space charge density sensors and a base station. The space charge density sensor based on atmospheric ion counter method is elaborated and developed, and the ARM microprocessor and Zigbee radio frequency module are applied. The wireless network communication quality and the relationship between energy consumption and transmission distance in the complicated electromagnetic environment is tested. Based on the experimental results, the proposed measurement system demonstrates that it can adapt to the complex electromagnetic environment under the UHVDC transmission lines and can accurately measure the space charge density.

Distribution systems can form islands when faults occur. Each island represents a subsection with variable boundaries subject to the location of a fault(s) in the system. A subsection with variable boundaries is referred to as island in this paper. For operation in autonomous mode, it is imperative to detect the island configurations and stabilize these subsections. This paper presents a novel scheme for the detection of islanding boundaries and stabilizing the system during autonomous operation. In the first stage, a boundary detection method is proposed to detect the configuration of the island. In the second stage a dynamic voltage sensitivity factor (DVSF) is proposed to assess the dynamic performance of the system. In the third stage, a wide area load shedding program is adopted based on DVSF to shed the load in weak busbars and stabilize the system. The proposed scheme is validated and tested on a generic 18-bus system using a combination of EMTDC/PSCAD and MATLAB softwares.

A novel high-voltage powerline inspection system is investigated, which consists of the cooperated ground vehicle and drone. The ground vehicle acts as a mobile platform that can launch and recycle the drone, while the drone can fly over the powerline for inspection within limited endurance. This inspection system enables the drone to inspect powerline networks in a very large area. Both vehicle’ route in the road network and drone’s routes along the powerline network have to be optimized for improving the inspection efficiency, which generates a new two-layer point-arc routing problem. Two constructive heuristics are designed based on “Cluster First, Rank Second” and “Rank First, Split Second”. Then local search strategies are developed to further improve the quality of the solution. To test the performance of the proposed algorithms, practical cases with different-scale are designed based on the road network and powerline network of Ji’an, China. Sensitivity analysis on the parameters related with the drone’s inspection speed and battery capacity is conducted. Computational results indicate that technical improvement on the inspection sensor is more important for the cooperated ground vehicle and drone system.

This paper identifies a criterion for choosing the largest set of rejected hypotheses in high-dimensional data analysis where Multiple Hypothesis testing is used in exploratory research to identify significant associations among many variables. The method neither requires predetermined thresholds for level of significance, nor uses presumed thresholds for false discovery rate. The upper limit for number of rejected hypotheses is determined by finding maximum difference between expected true hypotheses and false hypotheses among all possible sets of rejected hypotheses. Methods of choosing a reasonable number of rejected hypotheses and application to non-parametric analysis of ordinal survey data are presented.

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

Nanotechnology is an emerging field of modern science based on the use of nanoparticles (NPs) with a huge potential in many sectors, including nanomedicine. Their small size confers them unique properties because they are subject to physical laws that are in the middle between classical and quantum physics. In this context, NPs project plays a pivotal role because the composition, size, shape and surface proprieties need to be carefully considered for their optimal design and application. As reported in this review, NPs are classified in inorganic (metallic NPs; quantum dots; carbon-based nanostructures; mesoporous silica nanoparticles) and organic (liposomes and micelles, dendrimers and polymer nanoparticles) ones. Here, we report an accurate description of the potential of each NPs type focusing on their multiple areas of application like theranostics drug delivery, imaging, tissue engineering, antimicrobial techniques and nanovaccines, and therefore they represent a promise to revolutionize the new era of nanomedicine, especially in cancer research.

Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for approximately 80–90 % of all primary kidney cancer. Treatment for patients with advanced RCC remains unsatisfactory. Rare cancer stem cells (CSCs) are proposed to be responsible for failure of current treatment. Here, we investigate the effects of CBFA2T2 on CSCs regulation in RCC, as well as to elucidate the possible mechanisms. We showed that CBFA2T2 expression can significantly predict the survival of RCC patients. Functional assays showed that knocking-down of CBFA2T2 can inhibit cell migration and invasion in 786-O and A-498 cells in vitro, and reduce ALDH^high CSCs populations. Furthermore, CBFA2T2 expression is necessary for sphere-forming ability and cancer stem cells marker expression in RCC cell lines. Collectively, our data suggest that CBFA2T2 expression correlates with aggressive characteristics of RCC and CBFA2T2 is required for maintenance of “stemness” through regulation of stem cells factors, thereby highlighting CBFA2T2 as a potential therapeutic target for RCC treatment.

Long-term, high-accuracy mapping of built-up land dynamics is essential for understanding urbanization and its consequences for the environment. Despite advances in remote sensing and classification algorithms, built-up land mapping using early satellite imagery (e.g., from the 2000s and earlier) remains prone to uncertainty. We mapped the extent of built-up land in the North China Plain, one of China’s most important agricultural regions, from 1990 to 2019 at three-year intervals. Using dense time-stack Landsat data, we applied discrete Fourier transformation to create temporal predictors and reduce mapping uncertainties for early years. We improved overall accuracy by 8% compared to using spectral and indices predictors alone. We implemented a temporal correction algorithm to remove inconsistent pixel classifications, further improving accuracy to a consistently high level (>94%) across years. A cross-product comparison showed that our study achieved the highest levels of accuracy across years. Total built-up land in the North China Plain increased from 37,941 km² in 1990–1992 to 131,578 km² in 2017–2019. Consistent, high-accuracy built-up land mapping provides a reliable basis for policy planning in one of the most rapidly urbanizing regions of the planet.

We synthesized a small series of five 3-[4-arylmethoxy)phenyl]propanoic acids using an easy and short step synthetic route. All compounds were tested in vitro against a set of four protein targets identified as key elements in diabetes: GPR40, aldose reductase (AKR1B1), PPARγ and GLUT-4. Compound 1 displayed an EC₅₀ value of 0.075 μM against GPR40 and was an AKR1B1 inhibitor, showing IC₅₀ = 7.4 μM. Compounds 2 and 3 behave as AKR1B1 inhibitors, GPR40 agonists and showed an increase of 2 to 4-times in the mRNA expression of PPARγ, as well as the GLUT-4 levels. Docking studies were conducted in order to explain the polypharmacological mode of action and the interaction binding mode of the most active compounds on these targets. Compounds 1-3 were tested in vivo at 100 mg/kg dose, being 2 and 3 orally actives, reducing glucose levels in a non insulin-dependent diabetes mellitus mice model. Compounds 2 and 3 showed robust in vitro and in vivo efficacy, and could be considered as promising multitarget antidiabetic drug candidates. This is the first report of a single molecule with these four polypharmacological target action.

The peroxiredoxin (PRDX) family, a new family of proteins with a pivotal antioxidative function, is ubiquitously synthesized and abundantly identified in various organisms. In contrast to the intracellular localization of other family members (PRDX1/2/3/5/6), PRDX4 is the only known secretory form and protects against oxidative damage by scavenging reactive oxygen species in both the intracellular (especially the endoplasmic reticulum) compartments and the extracellular space. Recently, we generated unique human PRDX4 (hPRDX4) transgenic (Tg) mice on a C57BL/6J background and investigated the critical and diverse protective roles of PRDX4 against diabetes mellitus, atherosclerosis, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) as well as evaluated its role in the intestinal function in various animal models. Our published data have shown that PRDX4 helps prevent the progression of metabolic syndrome by reducing local and systemic oxidative stress and synergistically suppressing steatosis, inflammatory reactions, and/or apoptotic activity. These observations suggest that Tg mice may be a useful animal model for studying the relevance of oxidative stress on inflammation and the dysregulation of lipid/bile acid/glucose metabolism upon the progression of human metabolic syndrome, and that specific accelerators of PRDX4 may be useful as therapeutic agents for ameliorating various chronic inflammatory diseases.

The aim of this study was to examine oxidative stress and low level of alpha-1-antitrypsin (A1AT) in primary Sjögren's syndrome (pSS), and evaluate the associated autoreactivity against unmodified and their 4-hydroxy-2-nonenal (HNE)-modified peptides with pSS. Two differentially expressed proteins, alpha-1-acid glycoprotein 1 (A1AG1) and A1AT, exhibited 2-fold differences, and their HNE modifications were identified by depleted-albumin and immunoglobulin G (IgG) serum protein, in-solution digestion, in-gel digestion, and nano-LC-MS/MS from pSS patients and age-matched healthy controls (HCs). Furthermore, levels of proteins, confirmation of HNE modifications, HNE-protein adducts and autoreactivity against unmodified and their HNE-modified peptides were further validated. Levels of the HNE-protein adduct and A1AG1 were significantly higher in pSS patients than HCs, but levels of A1AT were significantly lower in pSS patients compared to HCs. Only the HNE modification of A1AT was confirmed. Further, concentrations of anti-A1AT^50-63 IgG and anti-A1AT^50-63 HNE IgA were significantly lower in pSS patients than HCs. Our study suggests that elevated HNE-protein adduct, oxidative stress, level [odds ratio (OR) 4.877, p = 0.003], lowered A1AT level (OR 3.910, p = 0.010) and a decreased level of anti-A1AT^50-63 IgG (OR 3.360, p = 0.010) showed an increased risk in pSS patients compared to HCs, respectively.

The dependence of the critical temperature $T_c$ of high-temperature superconductors of various families on their composition and structure is proposed. A clear dependence of the critical temperature of high-temperature superconductors (hydrides, Hg- and Y-based cuprates) on the serial number of the constituent elements, their valence and crystal lattice structure has been revealed. For cuprates, it is shown that it is possible to obtain even higher temperatures of superconducting transitions at normal pressure by implanting mercury atoms into the crystal lattice of cuprate.

The three-dimensional single fin configuration finds application in an intake geometry where the cowl-shock wave interacts with the side-wall boundary-layer. Accurate numerical simulation of such three-dimensional shock/turbulent boundary-layer interaction flows, which are characterized by the appearance of strong crossflow separation, is a challenging task. Reynolds-averaged Navier-Stokes computations using the shock-unsteadiness modified Spalart-Allmaras model is carried out at Mach of 5 at large fin angle of 23^◦. The computed results using the modified model are compared to the standard Spalart-Allmaras model and validated against the experimental data. The focus of work is to implement the modified model and to study the flow physics in detail in the complex region of swept-shock-wave turbulent boundary-layer interaction in terms of the shock structure, expansion fan, shear layer and the surface streamlines. The flow structure is correlated to the wall pressure and skin friction in detail. It is observed that the standard model predicts an initial pressure location downstream of the experiments. The modified model reduces the eddy viscosity at the shock and predicts close to the experiments. Overall, the surface pressure using modified model is predicted accurately at all the locations. The skin friction is under predicted by both the models in the reattachment region and is attributed to the poor performance of turbulence models due to flow laminarization.

Based on a modified dice-and-fill technique, a PIN-PMN-PT single crystal 1-3 composite with the kerf of 12 μm and pitch of 50 μm was prepared. The as-made piezoelectric composite material behaved with high piezoelectric constant (d33 = 1500 pC/N), high electromechanical coefficient (kt = 0.81), and low acoustic impedance (16.2 Mrayls). Using lithography and flexible circuit method, a 48-element phased array was successfully fabricated from such a piezoelectric composite. The array element was measured to have a central frequency of 20 MHz and a fractional bandwidth of approximately 77% at −6 dB. Of particular significance was that this PIN-PMN-PT single crystal 1-3 composite-based phased array exhibits a superior insertion loss compared with PMN-PT single crystal and PZT-5H-based 20 MHz phased arrays. The focusing and steering capabilities of the obtained phased array were demonstrated theoretically and experimentally. These promising results indicate that the PIN-PMN-PT single crystal 1-3 composite-based high frequency phased array is a good candidate for ultrasound imaging applications.

Significant problems have arisen in the last years, such as climate change, global warming, and hunger. These complications are correlated with the depletion and exploitation of natural resources and environmental contamination. Due to overcrowding, the list of challenges for the next few years is growing. A comprehensive approach was made to the agro-industrial production of Avocado (Persea americana) and the management of all its biomass waste. So, bioprocesses and biorefinery can be used to produce high added-value products. A large number of residues are composed of lignin and cellulose. They have many potentials to be exploited sustainably for chemical and biological conversion; physical, chemical, and natural treatments improve the following operations. There are some applications to many fields such as pharmaceutical, medical, material engineering, and environmental remediation. Possible pathways are mentioned to take advantage of Avocado as biofuels, drugs, bioplastics, and even in the environmental part and emerging technologies such as nanotechnology using bioprocesses and biotech. In conclusion, Avocado and its waste could be transformed into high value-added products in industries above to mitigate global warming and save non-renewable energy.

Immune checkpoint inhibitors (ICIs) have obtained durable responses in many cancers, making it possible to foresee their potential in improving the health of cancer patients. However, immunotherapies are limited at the moment to a minority of patients and there is a need for a better understanding of the basic molecular mechanisms and functions of pivotal immune regulatory molecules. Immune checkpoint cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and regulatory T (Treg) cells play pivotal roles in hindering the anticancer immunity. Treg cells suppress antigen-presenting cells (APCs) by depleting immune stimulating cytokines, producing immunosuppressive cytokines and constitutively expressing CTLA-4. CTLA-4 molecules bind with higher affinity to CD80 and CD86 than CD28 and act as competitive inhibitors of CD28 in APCs. The purpose of this review is to summarize state-of-the-art understanding of the molecular mechanisms underlining CTLA-4 immune regulation and the correlation of ICI response with CTLA-4 expression in Treg cells from preclinical and clinical studies for possibly improving CTLA-4-based immunotherapies, while highlighting the knowledge gap.

High-Intensity Functional Training (HIFT) is a novel exercise intervention that may test body systems in a balanced and integrated fashion by challenging individuals’ abilities to complete mechanical work. However, research has not previously determined if physical work capacity is unique to traditional physiologic measures of fitness. Twenty-five healthy men and women completed a six-week HIFT intervention with physical work capacity and various physiologic measures of fitness assessed pre- and post-intervention. At baseline, these physiologic measures of fitness (e.g., aerobic capacity) were significantly associated with physical work capacity and this relationship was even stronger at post-intervention assessment. Further, there were significant improvements across these physiologic measures in response to the delivered intervention. However, the change in these physiologic measures failed to predict the change in physical work capacity induced via HIFT. These findings point to the potential utility of HIFT as a unique challenge to individuals’ physiology beyond traditional resistance or aerobic training. Elucidating the translational impact of increasing work capacity via HIFT may be of great interest to health and fitness practitioners ranging from strength/conditioning coaches to physical therapists.

Integrated ultra-low-loss waveguides are highly desired for integrated photonics to enable applications that require long delay lines, high-Q resonators, narrow filters, etc. Here we present an ultra-low-loss silicon waveguide on 500 nm thick SOI platform. Meter-scale delay lines, million-Q resonators and tens of picometer bandwidth grating filters are experimentally demonstrated. We design a low-loss low-reflection taper to seamlessly integrate the ultra-low-loss waveguide with standard heterogeneous Si/III-V integrated photonics platform to allow realization of high-performance photonic devices such as ultra-low-noise lasers and optical gyroscopes.

Background: Some patients who have recovered from COVID-19 have experienced a range of persistent symptoms or the appearance of new ones after a SARS-CoV-2 infection. These symptoms can last from weeks to months, impacting everyday functioning to a significant number of patients. Methods: A cross-sectional analysis based on an online, self-reporting questionnaire was conducted in Ecuador from April to July 2022. Participants were invited by social media, radio, and TV to voluntarily participate in our study. A total of 2103 surveys were included in this study. We compared socio-demographic variables and long-term persisting symptoms at low (&lt; 2,500 m) and high altitude (&gt;2,500 m).Results: Overall, 1100 (52.3%) responders claimed to have long-term symptoms after SARS-CoV-2 infection. Most of these symptoms were reported by women (64.0%), the most affected group was young adults (68.5%), and the majority of long-haulers were mestizos (91.6%). We found that high altitude residents were more likely to report persisting symptoms (71.7%) versus those living at lower altitudes (29.3%). The most common symptoms were fatigue or tiredness (8.4%), hair loss (5.1%) and difficulty concentrating (5.0%). The highest proportion of persisting symptoms was observed among those who received an incomplete vaccine scheme.Conclusions: This is the first study describing post-COVID symptoms' persistence in low and high-altitude residents. Our findings demonstrate that women, especially those aging between 20-40, are more likely to describe sequalae associated with post-COVID. We also found that living at a high altitude was associated with earlier onset and longer symptom duration. Finally, we found a greater risk to report long lasting symptoms among women, those with previous comorbidities and those who had a severer acute SARS-CoV-2 infection.

Topology optimization is a pioneering design method that can provide various candidates with high mechanical properties. However, the high-resolution for the optimum structures is highly desired, normally in turn leading to computationally intractable puzzle, especially for the famous Solid Isotropic Material with Penalization (SIMP) method. In this paper, an efficient and high-resolution topology optimization method is proposed based on the Super-Resolution Convolutional Neural Network (SRCNN) technique in the framework of SIMP. The SRCNN includes four processes, i.e. refining, path extraction & representation, non-linear mapping, and reconstruction. The high computational efficiency is achieved by a pooling strategy, which can balance the number of finite element analysis (FEA) and the output mesh in optimization process. To further reduce the high computational cost of 3D topology optimization problems, a combined treatment method using 2D SRCNN is built as another speeding-up strategy. A number of typical examples justify that the high-resolution topology optimization method adopting SRCNN has excellent applicability and high efficiency for 2D and 3D problems with arbitrary boundary conditions, any design domain shape, and varied load.

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

Understanding of the decisive role of the interaction mechanism and kinetics in the combustion processes is highly relevant for the elaboration of optimal conditions for obtaining Mo-Cu composite powders. From this perspective, the efficient delivery of the reduction mechanism of copper and molybdenum oxides with combined Mg + C reducing agents at high heating rates is crucial to develop a valuable approach for the combustion synthesis of Mo-Cu composite powders. Herein, we shed light on the mechanism of the reactions in all the studied binary, ternary and quaternary systems contemporaneously demonstrating the effect of the heating rate on the conversion degree. The combination of two highly exothermic and speedy reactions (MoO3+3Mg and CuO+Mg vs MoO3+CuO+4Mg) led to a slow interaction with weak self-heating (dysynergistic effect) due to a change in the reaction mechanism. On the other hand, it has been shown that during the simultaneous utilization of the Mg and C reducing agents, the process begins exclusively with carbothermic reduction, and at relatively high temperatures it continues with magnesiothermic one. The effective activation energy values of the magnesiothermic stages of the studied reactions were determined by Kissinger isoconversional method.

This research focuses on the effect of trampling on vegetation in high-mountain ecosystems through the electromagnetic spectrum’s interaction with plant pigments, cell structure, water content and other substances that have a direct impact on leaf properties. The most heavily visited part of the High Tatras in Poland was divided into polygons and, after selecting the dominant species within alpine swards, a detailed analysis of trampled and reference patterns was performed. An ASD FieldSpec 3 was used to acquire high-resolution spectral properties of plants, their fluorescence and the leaf chlorophyll content with the ts-ta temperature index and fraction of accumulated radiation in the range of photosynthesis (fAPAR) used as reference data. The results show that, along tourist trails, vegetation adapts to trampling with the impact depending on the species. A lower chlorophyll value was confirmed by a decrease in fluorescence, and the state of cellular structures was degraded in trampled compared to reference species, with a lower leaf reflectance. Also, at the extreme, trampling can eliminate certain species such as Luzula alpino-pilosa.

Lattice and code cryptography can replace existing schemes such as Elliptic Curve Cryptography because of their resistance to quantum computers. In support of public key infrastructures, the distribution, validation and storage of the cryptographic keys is then more complex to handle longer keys. This paper describes practical ways to generate keys from physical unclonable functions, for both lattice and code based cryptography. Handshakes between client devices containing the PUFs and a server are used to select sets of addressable positions in the PUFs, from which streams of bits called seeds are generated on demand. The public and private cryptographic key pairs are computed from these seeds together with additional streams of random numbers. The method allows the server to independently validate the public key generated by the PUF, and act as a certificate authority in the network. Technologies such as High performance computing, and graphic processing units can further enhance security by preventing attackers to make this independent validation when only equipped with less powerful computers.

Farmers and seed companies constantly require high-quality seeds with excellent agronomic performance. However, faced with environmental adversity, limited natural resources and increasing food demand around the globe, more attention has turned to improving crop plant production by implementing efficient strategies. Seed priming technology has shown promising biological improvements leading to suitable agronomic performance in crop plants under adverse environmental conditions. Seeds are subjected to controlled conditions that are conducive to complex physiological, biochemical, and molecular changes, conferring specific stress tolerance to subsequent germination and growth conditions. In this review paper, we aimed to study the recent approaches in the efficiency of hydropriming, osmopriming, chemopriming, hormopriming, nanopriming, matrix priming, biopriming, physical priming and hybrid priming procedures in the production of crop plants under environmental adversity, as well as their biological mechanism changes. All priming methods demonstrated relevant changes in the biological mechanism related to crop plant production by mitigating salinity effects, heavy metals, and flooding stress and enhancing chilling, heat, drought and phytopathogen tolerance. We strongly recommend that researchers combine multiple priming methods, known as hybrid priming, in their investigations to provide novel technologies and additional biological approaches to enhance the knowledge of crop plant science. Thus, the findings shed light on the use of seed priming technology as a key strategy to increase crop plant production under environmental adversity by acquiring stress tolerance and enhancing agronomic traits to meet the global food demand.

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

Sulfonated carbon was used as an efficient and reusable heterogeneous solid acid catalyst for the synthesis of biodiesel via esterification of oleic acid with methanol under high voltage conditions. Using an inexpensive and reusable catalyst, environmental benignity, excellent yields in short times, synthesis in atmospheric pressure and low temperature conditions are some of the important features of this protocol. In the final results were confirmed by GC.

This manuscript provides a new integrated view of the development of allergen-specific TH2 and the lack of their associated Treg cells in a unified model, justifying the need for IL-2 to correct allergy conditions.

This paper presents the systematic development and performance characterization of a non-proprietary 3D-printable ultra-high-performance fiber-reinforced concrete (UHPFRC) for digital construction. Several fresh and hardened properties of the developed 3D-printable UHPFRC matrix (without fiber) and composite (with 2% volume fraction of steel fibers) were evaluated and compared to that of conventionally mold-cast UHPFRC. Additionally, the effects of testing direction on the compressive and flexural strengths of the printed UHPFRC were investigated. The fresh properties of the UHPFRC developed in this study satisfied the criteria for extrudability, buildability, and shape-retention-ability, which are relevant for ensuring printability. The printed UHPFRC exhibited superior flexural performance to the mold-cast UHPFRC due to alignment of the short fibers in the printing direction. The high compressive and flexural strengths, along with the deflection-hardening behavior, of the developed UHPFRC can enable the production of thin 3D-printed components with significant reduction or complete elimination of conventional steel bars.

Background: Extremely rare progressive diseases like Sedaghatian-type Spondylometaphyseal Dysplasia (SSMD) can be neonatally lethal and therefore go undiagnosed or are difficult to treat. Recent sequencing efforts have linked this disease to mutations in GPX4, with consequences in the resulting enzyme, glutathione peroxidase 4. This offers potential diagnostic and therapeutic avenues for those suffering from this disease, though the steps toward these treatments is often convoluted, expensive, and time-consuming. Main body: The CureGPX4 organization was developed to promote awareness of GPX4-related diseases like SSMD, as well as support research that could lead to essential therapeutics for patients. We provide an overview of the 21 published SSMD cases and have compiled additional sequencing data for four previously unpublished individuals to illustrate the genetic component of SSMD, and the role of sequencing data in diagnosis. We outline in detail the steps CureGPX4 has taken to reach milestones of team creation, disease understanding, drug repurposing, and design of future studies. Conclusion: The primary aim of this review is to provide a roadmap for therapy development for rare, ultra-rare, and difficult to diagnose diseases, as well as increase awareness of the genetic component of SSMD. This work will offer a better understanding of GPx4-related diseases, and help guide researchers, clinicians, and patients interested in other rare diseases find a path towards treatments.

Crimean-Congo hemorrhagic fever virus (CCHFV) is the causative agent of a tick-borne infection with significant mortality rate of up to 40% in the endemic areas, with evidence for geographical expansion. Lacking effective therapeutics and control measures, the development of protective CCHFV vaccine remains a crucial public health task. This manuscript describes, for the first time, a Bovine herpesvirus type 4 (BoHV-4) based viral vector (BoHV4-∆TK-CCHFV-N) and its immunogenicity and protection potential in BALB/c and IFNAR^-/- mice models in comparison with Adenovirus type 5 (Ad5-N) and pCDNA3.1 myc/His A (pCD-N1), two widely used vaccine platforms. All constructs expressing viral nucleocapsid (N) protein successfully elicited cytokine and total/specific antibody responses in BALB/c mice. BoHV4-∆TK-CCHFV-N and Ad5-N constructs further produced 100% protection in IFNAR^-/- mice during CCHFV Ank-2 strain lethal challenge. Despite elevated specific antibody responses in both animal models, the produced antibodies were unable to neutralize the virus in vitro. A comparison of delivery platforms was not possible, due to similar protection rates in IFNAR^-/- mice. In conclusion, vector-based CCHFV N protein expression proved to constitute an effective approach for the vaccine development pipeline and BoHV-4 emerged as a strong alternative to previously-used virus vectors.

The aim of this research is to determine the factors that may prevent high school students from participating in recreational activities and to investigate whether these factors differ within the scope of various variables. This study consisted of total 1459 (681 women and 778 men) student volunteers who educated in high school level. Sampling method was preferred for easy sampling. The face-to-face survey method was used to collect the data. The "Leisure Constraints Scale" developed by Alexandris and Carroll (1997) and adapted to Turkish by Gürbüz, Öncü, and Emir (2012) was used to determine the factors that might prevent individuals from participating in leisure activities. The data obtained for the research were first transferred to the computer and then analyzed by SPSS packet program. The error margin level in the study was taken as p<0.05. The cronbach alpha of the study was found to be 0.91. As a result, it was found that women participated in the leisure time more than men. It was also observed that the participants met with more leisure constrain in Turkey's eastern regions.

Evaluation of the effect of a high frequency acceleration device on clear aligner exchange intervals and treatment time required to achieve prescribed tooth movements. Sixteen subjects with similar Class I malocclusions, 5mm or less crowding, and treated with Invisalign were divided into two groups. Group 1 (experimental; N=8) underwent aligner treatment in conjunction with daily use of the high frequency acceleration device and exchanged aligners every 5 days. Group 2 (controls; N=8) underwent aligner treatment without use of the device and exchanged aligners every 14 days according to the manufacturer's recommended interval. All subjects were treated by one investigator, and results were evaluated by both; total number of aligners used, and number of refinements required, prior to final Vivera retention scan. A significant decrease in both treatment time, and number of aligners required to complete treatment was observed by experimental subjects as compared to controls. In addition, no refinements were required by experimental subjects, whereas 6 of 8 of the control subjects required 1 or more refinements. Use of the high frequency acceleration device in conjunction with Invisalign treatment resulted in more predictable tooth movement and a significant decrease in the length of treatment.

Mostly populous city like Chennai is subjected to frequent flooding due to its complex nature of natural and man-made activities. From the analysis of the past records of flood events of 1943,1976,1985,2005 and 2008,it has been observed Adayar watershed is subjected to cataclysmic flooding in low-lying areas of the city and its suburbs because of inoperativeness of the local drainage system, rainfall associated with cyclonic activity, topography of the terrain, encroachments along the floodplain, hugh upstream flow discharge into the river and the highly impervious area which blocked the runoff to flow into the storm water drainage. After looking into these problems of flooding, a study have been conducted on Adayar watershed to develop a 2D hydrodynamic model for the two scenarios of existing condition of storm water drainage network and revised conditions of storm water drainage network using high resolution Lidar DEM to assess the volume of runoff with respect to time and duration on flood peaks for the two flood events of 2005 and 2015.Secondly to develop a 1D flood model to predict the river stages during peak floods using MIKE 11 for the Adayar watershed. Thirdly to integrate the coupled 1D and 2D model using MIKEFLOOD for assessing the extent of inundation in the floodplain area of Adayar river. Finally results from the integrated model have been validated and the results found satisfactory. As a part of mitigation measures, two flood mitigation measures have been adopted. One measure such as revised storm water drainage system which enhances the flood carrying capacity of the drains and results in less inundated area which solves the problem of urban flooding and second measure such as regrading the river bed which reduces the floodplain inundation around the adjacent area of the river. After adopting these measures, the river is free to flow into the sea without any blockades.

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

We demonstrate an RF photonic fractional Hilbert transformer based on an integrated Kerr micro-comb source featuring a record low free spectral range of 49 GHz. By programming and shaping the comb lines according to calculated tap weights for up to 39 wavelengths across the C-band, we achieve tunable bandwidths ranging from 1.2 to 15.3 GHz as well as variable center frequencies from baseband to 9.5 GHz, for both standard integral and arbitrary fractional orders. We experimentally characterize the RF amplitude and phase response of the tunable bandpass and lowpass Hilbert transformers with 90 and 45-degree phase shifts. The experimental results show good agreement with theory, confirming the effectiveness of our approach as a powerful way to implement standard and fractional order Hilbert transformers with broad and variable bandwidths and center frequencies, with high reconfigurability and greatly reduced size and complexity. Tan, and D. J. Moss are with the Optical Sciences Centre, Swinburne University of Technology, Hawthorn, VIC 3122, Australia. (Corresponding e-mail: dmoss@swin.edu.au). Xu is with the Electro-Photonics Laboratory, Department of Electrical and Computer System Engineering, Monash University, Clayton, 3800 VIC, Australia

When extract building from high resolution remote sensing image with meter/sub-meter accuracy, the shade of trees and interference of roads are the main factors of reducing the extraction accuracy. Proposed a Bayesian Convolutional Neural Networks(BCNET) model base on standard fully convolutional networks(FCN) to solve these problems. First take building with no shade or artificial removal of shade as Sample-A, woodland as Sample-B, road as Sample-C. Set up 3 sample libraries. Learn these sample libraries respectively, get their own set of feature vector; Mixture Gauss model these feature vector set, evaluate the conditional probability density function of mixture of noise object and roofs; Improve the standard FCN from the 2 aspect:(1) Introduce atrous convolution. (2) Take conditional probability density function as the activation function of the last convolution. Carry out experiment using unmanned aerial vehicle(UVA) image, the results show that BCNET model can effectively eliminate the influence of trees and roads, the building extraction accuracy can reach 97%.

A multiscale (micro-macro) approach is proposed for the establishment of the full thermal and induced stress fields in cracked composites that are subjected to heat flow. Both the temperature and stresses distributions are determined by the solution of a boundary value problem with one-way coupling. In the micro level and for combined thermomechanical loading, a micromechanical analysis is employed to determine the effective moduli, coefficients of thermal expansion and thermal conductivities of the undamaged composite. In the macro level, the representative cell method is employed according to which the periodic damaged composite region is reduced, in conjunction with the discrete Fourier transform, to a finite domain problem. As a result, a boundary value problem is obtained in the Fourier transform domain which is appropriately discretized and solved. The inverse transform and an iterative procedure provide the full thermal and stress fields. The proposed method is verified by comparisons with exact solutions. Applications are given for the determination of the thermal and stress fields in cracked fiber-reinforced polymeric composite, cracked porous ceramic material and cracked periodically layered ceramic composite caused by the application of heat flow. The presented formulation admits however the application of a combined mechanical and heat flux on cracked composites.

Increasing salt intake has substantial negative impacts on health and well-being. This review article focusses on the effect of salinity intrusion (SI) on the water quality and community health of coastal Bangladesh and to find out the effectiveness of interventions for reducing the negative effects of salinity. Saline water is a noteworthy reason for hypertension or high blood pressure in the coastal areas. Health status of women especially the pregnant women are vulnerable because of drinking water sodium (DWS) prompting to pre-eclampsia, high blood pressure and hypertension as well as infant mortality. Several interventions such as rainwater harvesting and Pond sand filter (PSF) system as well as managed aquifer recharge (MAR) usage and the integration of mixed sources were reviewed on the content of drinking water sodium (DWS). Although rainwater has the positive impact of low or no sodium intake on human health, it still possesses negative impacts from not having vital minerals. Despite what might be expected, in MAR a steady increment in sodium concentration through the span of the dry season was observed. It is, subsequently, important to increase awareness about drinking water sodium (DWS) intake by providing and adopting correct technological interventions.

Mineral dust is one of the most important aerosol in mass over the world, affecting health and dynamics. This aerosol is mainly emitted over arid areas but may be long-range transported, impacting the local budget of air quality in many cities. While models were extensively used to study a single specific event, or making a global analysis at coarse resolution, the goal of our study is to simultaneously focus on several areas - Europe, North America, Central Asia, East China and the Caribbean area - for a one month period, March 2014, avoiding any parameter fitting to better simulate a given dust outbreak. The simulation is performed for the first time with the hemispheric version of the CHIMERE model, with a horizontal resolution of 10km. In this study, an overview of several simultaneous dust outbreaks over the north hemisphere is proposed to assess the capability of such modelling tools to predict dust pollution events. A quantitative and qualitative evaluation of the most striking episodes is presented with comparisons to satellite data, ground based Particulate Matter and calcium measurements. Despite some overestimation of dust concentrations far from emission areas, the model is able to simulate the timing of the arrival of dust outbreaks on observational sites. For instance, several spectacular dust storms in the US and China are perfectly captured by the models. The high resolution allows to better describe and understand the orographic effects and the long-range transport of dust plumes.

A series of Si-bearing MgAl₂O₄-spinels were synthesized at 1500-1650 °C and 3–6 GPa. These spinels had SiO₂ contents up to ~1.03 wt%, and showed a substitution mechanism of Si⁴⁺ + Mg²⁺ = 2Al³⁺. Unpolarized Raman spectra were collected from polished single grains, and displayed a set of well-defined Raman peaks at ~610, 823, 856 and 968 cm^-1 which had not been observed before. Aided with the Raman features of natural Si-free MgAl₂O₄-spinel, synthetic Si-free MgAl₂O₄-spinel, natural low quartz, synthetic coesite, synthetic stishovite and synthetic forsterite, we infer that these Raman peaks should belong to the SiO₄ groups. The relations between the Raman intensities and SiO₂ contents of the Si-bearing MgAl₂O₄-spinels suggest that at some P-T conditions some Si must adopt the M-site. Unlike the SiO₄ groups with very intense Raman signals, the SiO₆ groups are largely Raman-inactive. We have further found that the Si cations primarily appear on the T-site at P-T conditions ≤ ~3–4 GPa and 1500 °C, but attain a random distribution between the T-site and M-site at P-T conditions ≥ ~5–6 GPa and 1630–1650 °C. This Si-disordering process observed for the Si-bearing MgAl₂O₄-spinels hints that similar Si-disordering might happen to the (Mg,Fe)₂SiO₄-spinels (ringwoodite), the major phase in the lower part of the mantle transition zone of the Earth and the index mineral for the very strong shock stage experienced by extraterrestrial materials. The likely consequences have been explored.

This paper reports a novel fabric phase sorptive extraction-high performance liquid chromatography-ultra violet detection (FPSE-HPLC-UV) method for the simultaneous extraction and analysis of four phenyltin derivatives that include triphenyltin hydroxide, triphenyltin acetate, triphenyltin chloride and tetraphenyltin in environmental water (agricultural waste water and municipal waste water) and canned food samples. The selected analytes were well resolved by Waters Nova pack C18 column (3.9 x 150 mm, 4 µm particle size) in isocratic elution mode within 15 minutes. The new microextraction media has been analytically evaluated using phenyltin derivatives as model compounds. The factors affecting the extraction efficiency of FPSE have been evaluated and the optimum extraction conditions were determined. Under these optimum conditions, the limits of detection (LODs) for sol-gel C18 coated fabric phase sorptive extraction (FPSE) media in combination with HPLC-UV for the analysis of the phenyltin derivatives were in the range of 10-100 ng/mL with high precision (low relative standard deviation) at 10 ng/mL concentration with good absolute recoveries. To the best of our knowledge, this is the first FPSE extraction procedure applied to environmental water and canned food samples for the simultaneous determination of phenyltin derivatives and could be readily adopted as a rapid and robust green analytical tool for routine environmental and food analytical laboratories.

The effect of low cycle fatigue (LCF) pre-damage on the subsequent very high cycle fatigue (VHCF) behavior is investigated in TC21 titanium alloy. LCF pre-damage is applied under 1.8% strain amplitude up to various fractions of the expected life and subsequent VHCF properties are determined using ultrasonic fatigue tests. Results show that 5% of LCF pre-damage insignificantly affects the VHCF limit due to the absent of pre-crack, but decreases the subsequent fatigue crack initiation life estimated by Pairs’ law. Pre-cracks introduced by 10% and 20% of LCF pre-damage significantly reduce the subsequent VHCF limits. The crack initiation site shifts from subsurface-induced fracture for undamaged and 5% of LCF pre-damage specimens to surface pre-crack for 10% and 20% of LCF pre-damage specimens in very high cycle region. The fracture mechanism analysis indicate that LCF pre-crack will re-start to propagate under subsequently low stress amplitude when stress intensity factor of pre-crack is larger than its threshold. Furthermore, the predicted fatigue limits based on EI Haddad model for the LCF pre-damage specimens well agree with the experimental results.

Toll-like receptors (TLRs) play a key role in the innate immune response to numerous pathogens, including Acanthamoeba sp. The aim of this study was to determine the expression of TLR2 and TLR4 in the eyes of mice following intranasal infection with Acanthamoeba sp. Amoebae used in this study were isolated from the bronchial aspirate of a patient with acute myeloid leukemia (AML) and atypical symptoms of pneumonia. We found statistically significant differences in the expression of TLR2 and TLR4 in the eyes of immunocompetent mice at 8, 16, and 24 days post Acanthamoeba sp. infection (dpi) compared to control. Immunosuppressed mice showed significant differences in the expression of TLR2 at 16 and 24 dpi compared to uninfected animals. Our results indicate that TLR2 and TLR4 are upregulated in the eyes of mice in response to Acanthamoeba sp. We suggest that it is possible for trophozoites to migrate through the optic nerve from the brain to the eyes.

Transplant of human cancer cells into zebrafish larvae has emerged as a useful methodology in cancer research. Zebrafish have very low husbandry costs, are amenable to large-scale drug screening, and are unmatched for optical clarity in live animal imaging. However, there is currently no consensus on the ideal methods for xenograft of human cancer cells into zebrafish. Here, we have examined the effects of transplant site and housing temperature on both zebrafish larvae and human cancer cells using survival analyses, metabolomic approaches, and in vivo imaging. Our data show that while zebrafish larvae can adapt to the ideal conditions for mammalian cells, human cancer cells are highly sensitive to both temperature change and transplant site. Human cells housed in slightly cooler than physiologic temperatures had a significantly altered metabolism that resulted in changes in growth, survival, and response to chemotherapy. Cancer cells xenografted into the yolk of the larvae also had reduced proliferation and drug response compared to those xenografted into the soma, in part due to the differences in metabolites available at these sites. In total, temperature and transplant site can have profound effects on xenografted cells. Standardization of zebrafish xenograft methods will enhance data reproducibility between individual laboratories.