Present contribution has consisted of a construction of a class of new shooting methods and application to Darcy Forchheimer fluid flow over the linearly stretching sheet under the influence of thermal radiations. Governing equations of the flow phenomena are presented in the form of partial differential equations, and these governing partial differential equations are reduced into ordinary differential equations. The final ordinary differential equations are resolved by the present given shooting method based on the class of Adam Moulton's techniques with the Gauss-Siedel iterative method. Since the system of the first-order differential is discretized by the Adam Moulton method with the Gauss-Siedel iterative method containing some unknown initial conditions, a shooting approach is employed for finding unknown initial conditions. Also, it is proved that the Adam Moulton methods using Gauss-Seidel iterative method are unconditionally stable for any system of differential equations. In additions to this, finite element simulations containing velocity profile, streamlines, temperature profile and temperature contours are deliberated with the help of graphs, and tables. Thus, the main aim of the current paper is to calculate the unique results for a coupling approach based on Adams Moulton's method for the boundary layer flow problem with the effect of heat transfer.
In this paper, we define a non-iterative transformation method for an Extended Blasius Problem. The original non-iterative transformation method, which is based on scaling invariance properties, was defined for the classical Blasius problem by T\”opfer in 1912. This method allows us to solve numerically a boundary value problem by solving a related initial value problem and then rescaling the obtained numerical solution. In recent years, we have seen applications of the non-iterative transformation method to several problems of interest. The obtained numerical results are improved by both a mesh refinement strategy and Richardson’s extrapolation technique. In this way, we can be confident that the computed six decimal places are correct.
The current work is devoted for operating the Lie symmetry approach, to coupled complex short pulse equation. The method reduces the coupled complex short pulse equation to a system of ordinary differential equations with the help of suitable similarity transformations. Consequently, these systems of nonlinear ordinary differential equations under each subalgeras are solved for traveling wave solutions. Further, with the help of similarity variable, similarity solutions and traveling wave solutions of nonlinear ordinary differential equation, complex soliton solutions of the coupled complex short pulse equation are obtained which are in form of sinh, cosh, sin and cos functions.
Background: Prostate cancer early detection (PCa-ED) trough prostatic specific antigen (PSA) and digital rectal examination (DRE) has proved to lower mortality rates and should be carry out by primary care physicians (PCP). In Mexico, 80% of prostate cancers are detected in advanced-stages but PCP trends on PCa-ED remain unknown. Aim: To assess PCP knowledge and skills regarding PCaED. Materials and Methods: A self-administrating survey about the knowledge and skills of PCa-ED was created and delivered to PCP. Logistic regression analysis was conducted for the propensity of PCP to test prostatic specific antigen (PSA) on asymptomatic men. Results: The survey was completed by 170 PCP. The 13.5% answered being “not-well trained”. Score on risk factors knowledge was 51.5±15.7% but a score above the mean was not associated with testing PSA on asymptomatic men (p=0.674). The 40.6% answered having an institutional program on PCa-ED and 86% having access to PSA testing. Testing PSA on asymptomatic men was found in 40%. Moreover, 61.2% do not perform any digital rectal examination for PCa-ED, and this was not associated with preventing factors like lack of space, time, and assistance (p>0.05). Fewer years in practice and being a family medicine resident was associated with a less likelihood of testing PSA in asymptomatic men whereas having access to PSA testing and an institutional program on PCa-ED, increased the probability. The only significantly associated factor in the multivariable model was to have access to PSA testing [OR: 3.36 (CI 95% 1.54-7.30) p=0.002]. Conclusions: A low proportion of PCP in southeast Mexico performs PCa-ED and uses concepts outside evidence-based recommendations. A national program on PCa-ED and continuing medical education for PCP is a promising strategy to improve PCa-ED.
Recent efforts to determine the high-resolution crystal structures for the adenosine receptors (A1R and A2AR) have utilized modifications to the native receptors in order to facilitate receptor crystallization and structure determination. One common modification is a truncation of the unstructured C-terminus, which has been utilized for all the adenosine crystal structures obtained to date. However, the C-terminus has been identified as a location for protein-protein interactions that may be critical for physiological function of these important drug targets. Here, we determine whether the presence of the full-length C-terminus affected downstream signaling using a yeast MAPK response-based fluorescence assay. Upon ligand binding, the A1Δ291R or A2AΔ316R variants were unable to couple to human-yeast chimeric G-protein chimeras to generate a downstream signal in yeast, though full-length receptors showed native-like G-protein coupling. Further, constructs transfected into mammalian cells (HEK-293) showed similar behavior – i.e. the variants with C-terminal truncations lacked cAMP-linked signaling compared to the full-length receptors. Although the C-terminus was essential for Gα protein- associated signaling, chimeras of A1R with a C-terminus of A2AR coupled to the A1R-specific Gα (i.e. Gαi1 versus Gαs). This surprising result suggests that the C-terminus is important in signaling, but not specificity, for the interaction with Gα protein. This result has further implications in drug discovery both in enabling the experimental use of chimeras for ligand design, and in cautious interpretation of structure-based drug design based on truncated receptors.
Background and Purpose. Despite widespread abuse of cocaine, there are no approved treatments for cocaine use disorder. Chronic cocaine use is associated with upregulated dopamine D3 receptor (D3R) expression in the brain, and therefore, most D3R-based medication development has focused on D3R antagonists. However, D3R antagonists do not attenuate cocaine intake under “easy” self-administration conditions when response requirements are low. Here we evaluated a novel, highly selective and metabolically stable D3R partial agonist, VK4-40, for its efficacy in reducing cocaine intake and relapse to drug seeking. Experimental Approach. The impact of VK4-40 on cocaine intake and relapse were evaluated using intravenous self-administration procedures under a fixed-ratio 2 reinforcement schedule and cocaine-primed reinstatement conditions in rats. Optogenetic brain-stimulation reward procedures were used to evaluate the interaction of VK4-40 and cocaine in the mesolimbic dopamine system. Sucrose self-administration and a conditioned place preference paradigm was used to evaluate the abuse potential of VK4-40 alone and other unwanted effects. Key Results. VK4-40 dose-dependently reduced cocaine self-administration and cocaine-primed reinstatement of drug-seeking behavior. In addition, VK4-40 inhibited cocaine-enhanced brain-stimulation reward caused by optogenetic stimulation of dopamine neurons in the ventral tegmental area. VK4-40 alone decreased brain-stimulation reward, and produced neither conditioned place preference nor place aversion. This new D3R partial agonist also failed to alter oral sucrose self-administration. Conclusions and Implications. The novel D3R partial agonist, VK4-40, attenuates cocaine reward and relapse in rodents, without significant unwanted effects. These findings support further investigation of D3R partial agonists as putative treatments for cocaine use disorder.
Widespread dispersal of progeny is expected to result in enough gene flow to maintain genetic homogeneity over large areas. Surveys of genetic markers in species with planktonic larvae have mostly confirmed this expectation. However, genetic structure has occasionally been found at small spatiotemporal scales and interpreted as evidence of restricted dispersal, natal homing, sweepstakes reproductive success, or natural selection. We investigated genetic population structure in blue crabs from the Atlantic and Gulf of Mexico coasts of North America. Sampling was most intensive from five estuaries along the coast of Louisiana, with megalopae, juveniles and adults sampled from 2010 to 2016. 1446 individuals were genotyped at 2486 SNPs in 1363 putative protein-coding loci. Levels of differentiation between locations were consistently low, but significant differentiation was found among locations and among years. No evidence was found for chaotic genetic patchiness or sweepstakes reproductive success: no genetic differentiation was detected among collections of megalopae and none of the sampled individuals were closely related. Our results indicate that gene flow in blue crabs maintains near genetic homogeneity from the northern Gulf of Mexico through the Atlantic coast of North America.
Nitrogen (N) and phosphorus (P) additions to grasslands increase aboveground plant biomass and modify plant community composition, thereby affect plant-derived organic carbon inputting to soil and soil C cycling and storage. However, the effects of nutrient additions on SOC decomposition and soil C sequestration have no census and their underlying mechanisms are poorly understood. This study aimed to explore the mechanisms underlying SOC decomposition and SOC content decline in the topsoil of Tibetan alpine meadows after nine-year field N and P additions. Soil and microbial stoichiometric characteristics were measured and priming effects (PEs), substrate decomposition, as well as microbial C use efficiency (CUE) by adding 13C labeled substrate (glucose or vanillin) were analyzed. N and P additions differentially affected the magnitude and direction of PEs and SOC decomposition, accelerated substrate mineralization of glucose by 33-45% and that of vanillin by 11-45%, but decreased microbial CUE of glucose by 9-15% and that of vanillin by 11-48%. This was associated with the N and P additions-induced lower soil ecological stoichiometric ratios and higher microbial C:N:P ratios compared with Control. Therefore, these comprehensive effects of N and P additions on decomposition of SOC and plant-derived C substrates reduced SOC sequestration and thus SOC content. Long-term N and P additions would weaken soil functioning as C pool of Tibetan alpine meadows.
Sequential model-based design of experiments (MBDoE) uses information from previous experiments to select run conditions for new experiments. Computation of the objective functions for popular MBDoE can be impossible due to a non-invertible Fisher Information Matrix (FIM). Previously, we evaluated a leave-out (LO) approach that design experiments by removing problematic model parameters from the design process. However, the LO approach can be computationally expensive due to its iterative nature and some model parameters are ignored. In this study, we propose a simple Bayesian approach that makes the FIM invertible by accounting for prior parameter information. We compare the proposed Bayesian approach to the LO approach for designing sequential A-optimal experiments. Results from a pharmaceutical case study show that the Bayesian approach is superior, on average, to the LO approach for design of experiments. However, for subsequent parameter estimation, a subset-selection-based LO approach gives better parameter values than the Bayesian approach.
Experimental results on pressure drop and flow patterns for gas-liquid flow through packed beds obtained in the International Space Station with two types of packing are presented and analyzed. It is found that the pressure drop depends on the packing wettability in the viscous-capillary (V-C) regime and this dependence is compared with previously published results developed using short duration low-gravity aircraft tests. Within the V-C regime, the capillary contribution is the dominant force contributing to the pressure drop for the wetting case (glass) versus the viscous contribution dominating for the non-wetting case (Teflon). Outside of the V-C regime, it is also found that hysteresis effects that are often strong in normal gravity gas-liquid flows are greatly diminished in microgravity and pressure drop is nearly independent of packing wettability. A flow pattern transition map from bubble to pulse flow is also compared with the earlier aircraft data.
Emerging pathogens have been an eternal threat to mankind. In a series of pandemics caused by notorious coronaviruses, a newly emerged virus is creating panic among world population. Originating in late December, 2019 from Wuhan, China, the SARS-CoV-2 is spreading its terror throughout the world. The virus is rapidly transmitted due to unavailability of effective theranostics. In this study, multiple sequence alignment of SARS-CoV-2 spike protein was done and four novel inserts were found in comparison to SARS-CoV. Using computational informatics tool viz. IEDB B-cell epitopes prediction tool, B-cell immunogenic epitopes of SARS-CoV-2 spike protein was predicted. Five novel potent epitopes i.e. ‘71SGTNGTKRFDN81, 247SYLTPG252, 634RVYST638, 675QTQTNSPRRARSV687 and 1054QSAPH1058 were selected as antigenic determinants and their docking with the 3D structure of ACE2 receptor was delineated. The quantum of information generated by this study will prove beneficial for development of effective therapeutics, diagnostics and multiepitopic vaccines to combat this ongoing menace.
Background and purpose: Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome- Coronavirus 2 (SARS-CoV2) is a highly contagious disease that has infected more than 200,000 patients and led to more than 10000 deaths in 166 countries in less than four months. New medications are needed to combat this disease. Since the process of discovery, development and approval of new drugs is long, old drugs can be repurposed for treatment of COVID-19. Oseltamivir is used for management of COVID-19 and Influenza A. Rimantadine is an alternative drug to oseltamivir for management of influenza A. Therefore, it is possible that rimantadine can be used for management of COVID-19 as an alternative to oseltamivir. The purpose of the study is to verify the potential of rimantadine as a drug for COVID-19 Methods: The SARS-CoV2 nucleocapsid was downloaded from the Protein databank and the chemical structure of rimantadine downloaded from Pubchem. Molecular docking of the nucleocapsid as the receptor and rimantadine as the ligand was done using avogadro and chimera software. Prediction of pharmacokinetic properties was done using SWISSADME website while the toxicity properties predicted using the ProTox server. Results: The interactions between rimantadine and the SARS-CoV2 nucleocapsid involved conventional hydrogen bonding with threonine & asparagine; attractive charge interaction with aspartate and Pi-alkyl interaction with tryptophan. Rimantadine has high gastrointestinal activity, very few drug-drug interactions and is relatively safe. Conclusion: Rimantadine binds to the SARS-CoV2 nucleocapsid and can thus be used for management of COVID-19. Keywords: Rimantadine, COVID-19, SARS-CoV2, Oseltamivir
To understand the growth response to drought, we performed a proteomics study in the leaf growth zone of maize (Zea mays L.) seedlings and functionally characterized the role of starch biosynthesis in the regulation of growth, photosynthesis and antioxidant capacity, using the shrunken2 mutant (sh2), defective in ADP-glucose pyrophosphorylase. Drought induced differential expression of 284 proteins overrepresented for photosynthesis, amino acids, sugar and starch metabolism, and redox-regulation. Changes in protein levels correlated with enzyme activities (increased ATP synthase, cysteine synthase, starch synthase, RuBisCo, peroxiredoxin, glutaredoxin, thioredoxin and decreased triosephosphate isomerase, ferredoxin, cellulose synthase activities, respectively) and metabolite concentrations (increased ATP, cysteine, glycine, serine, starch, proline and decreased cellulose levels). The sh2 mutant had a reduced ability to increase starch levels under drought conditions, causing soluble sugar starvation at the end of the night and impaired leaf growth. Increased RuBisCo activity and pigment concentrations observed in WT in response to drought were lacking in the mutant, which suffered more oxidative damage and recovered more slowly after re-watering. These results demonstrate that starch biosynthesis plays a crucial role in maintaining leaf growth under drought stress and facilitates enhanced carbon acquisition upon recovery.
Objective To compare the safety and efficacy of Veregen® ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). Design A Phase II randomised control trial. Setting A tertiary gynaecological oncology referral center. Population All women diagnosed with primary and recurrence uVIN. Methods Eligible patients were randomised to receive either Veregen® or placebo ointment (applied 3 times daily for 16 weeks), and were followed up at 2, 4, 8, 16, 32 and 52 weeks. Main outcome measures Outcome measures, recorded at 16 and 32 weeks, were histological (HR) and clinical (CR) response (as measured by ≥30% reduction in the sum of the longest diameter of all lesions when compared to baseline), toxicity and changes in quality of life and pain scores. Results 26 patients were randomised and all 13 patients who received Veregen® showed either complete (n=5) or partial (n=8) CR with a trend towards an improvement in baseline symptoms. In placebo group, 3 patients had complete CR, 2 had partial CR and 6 had stable disease. Patients in the Veregen® group showed a significant improvement in CR as compared to the placebo group (P=0.0026). There was no evidence of difference in HR and toxicity reported in both groups. Conclusion Our study indicates that Veregen application is safe and leads to at least a partial clinical resolution of uVIN lesions and symptoms improvement, thus warranting a phase III multi-centre RCT.
Although cell wall polymers play important roles in the tolerance of plants to abiotic stress, the effects of salinity on cell wall composition and metabolism in grasses remain largely unexplored. Here, we conducted an in-depth study of changes in cell wall composition and phenolic metabolism induced upon salinity in maize seedlings and plants. Cell wall characterization revealed that salt stress modulated the deposition of cellulose, matrix polysaccharides and lignin. The extraction and analysis of arabinoxylans by size-exclusion chromatography, two-dimensional NMR spectroscopy and carbohydrate gel electrophoresis showed a reduction of arabinoxylan content in salt-stressed roots, with no changes in xylose/arabinose ratios. Saponification and mild acid hydrolysis followed by RP-HPLC analysis revealed that salt stress also reduced the feruloylation of arabinoxylans. Determination of lignin content and composition by nitrobenzene oxidation and two-dimensional NMR confirmed the increased incorporation of syringyl units in lignin polymer. Our data also revealed the induction of the expression of genes and enzymes enrolled in phenylpropanoid biosynthesis under salinity. The UPLC-MS-based metabolite profiling confirmed the modulation of phenolic profiling by salinity and the accumulation of ferulate and its derivatives 3- and 4-O-feruloyl quinate. In conclusion, we present a model for explaining cell wall remodeling in response to salinity.
Due to the urbanization and human invasion of the natural environments, a great deal of changes have occurred on the food composition and feeding ecology of several animals especially those are sharing humans their habitats in fields, wadis and gardens. The Desert Hedgehogs Paraechinus aethiopicus populations inhabiting different localities in Saudi Arabia were studied by using stomach contents analysis between February 2015 and October 2019. Precise analysis of 55 stomach contents of hedgehogs showed that the food of The Desert Hedgehogs Paraechinus aethiopicus is highly diverse and highly influenced with effect of humans on the environment includes cooked rice, insects, plant materials, egg shells, worms, garbage and remains of mammals and birds. Diet composition showed seasonal variations that are apparently associated with changes in the availability of different food items. The present results clearly showed that The Desert Hedgehogs Paraechinus aethiopicus is a generalist animal, capable of adapting to a great variety of dietary compositions in the study sites.
Abstract: In this paper the feeding index (FI), Gastro somatic index (GaSI) and Food Prevalence Index (FPI) of freshwater prawn M. assamense peninsulare were evaluated to assess the quantity and kind of food which this prawn consumes in the Rawasan stream. A total of 401 prawns were collected for an interval of two years form five selected site in Rawasan stream of Garhwal in Central Himalaya, India from August 2013 to July 2015. Collected prawn was in the size range of 20-75 mm in male and 24-65 mm in female in total length during the study period. The stomach contents of 10 collected specimens were examined monthly and observed that 35% of the stomach was full or semi-full and 15% stomach were empty. Highest Gastro somatic value (Mean±SE) was obtained 2.95±0.80 during June in the male and 3.25±0.44 during May in the female. After that, it gradually decreased in both the sex and this repeated in cyclic pattern each year. More or less a similar trend was reported in the feeding index value during the study indicate a significant relationship between feeding intensity and Gastro somatic index. Highest Food Prevalence Index (FPI) was seen in fragment of animals in both sex, which was (88.48) in male and (58.26) in female prawn and lowest FPI value in sand debris 7.9 and 5.7 in male & female prawn respectively. Main food items were fragment of plants & animal, diatoms, algae, and sand. In overall, the results show that this prawn is selectively abstemious
When establishing a hypothesis testing procedure to ensure its credibility, the most significant step is unquestionably to select and/or compute the optimal type-I and type-II error probabilities, namely the producer’s and consumer’s risks, or α & β errors, respectively if the research hypothesis is set to be a good product vs bad. This article is fundamentally opposed to conventionally and judgmentally picking at best a subjective type-I error probability (α error) and it therefore outlines a game theoretic approach, i.e. that of von Neumann, to this historically century-old unresolved paradigm to justify optimal choices when relevant market-centric factors such as cost and utility are incorporated for input data. A game theory-based algorithmic methodology and several detailed numerical examples of practical nature with specific emphasis to company-specific acceptance sampling plans (including a simple hospital scenario) for quality control are studied. A side benefit of this method, in addition to improving the enterprise acceptance sampling plans, is to transform the traditional hypothesis testing procedure so as to make sound engineering decisions from a “subjective” to an “objective” stance, provided that the monetary cost and utility values as consequences to committing error and non-error combinations are available.