Applications of bioconvection for tiny particles due to two concentric cylinders when role of Lorentz force is significant.

The bioconvection flow of tiny fluid conveying the nanoparticles has been investigated between two concentric cylinders. The contribution of Lorenz force is also focused to inspect the bioconvection thermal transport of tiny particles. The tiny particles are assumed to flow between two concentric cylinders of different radii. The first cylinder remains at rest while flow is induced due to second cylinder which rotates with uniform velocity. Furthermore, the movement of tiny particles follows the principle of thermophoresis and Brownian motion as a part of thermal and mass gradient. Similarly, the gyro-tactic microorganisms swim in the nanofluid as a response to the density gradient and constitute bio-convection. The problem is modeled by using the certain laws. The numerical outcomes are computed by using RKF -45 method. The graphical simulations are performed for flow parameters with specific range like 1≤Re≤5, 1≤Ha≤5, 0.5≤Nt≤2.5, 1≤Nb≤3, 0.2≤Sc≤1.8, 0.2≤Pe≤1.0 and 0.2≤Ω≤1.0. It is observed that the flow velocity decreases with the increase in the Hartmann number that signifies the magnetic field. This outcome indicates that the flow velocity can be controlled externally through the magnetic field. Also, the increase in the Schmidt numbers increases the nanoparticle concentration and the motile density.

Molecular Inversion Probe-Based Sequencing of USH2A Exons and Splice Sites as a Cost-Effective Screening Tool in USH2 and arRP Cases.

A substantial proportion of subjects with autosomal recessive retinitis pigmentosa (arRP) or Usher syndrome type II (USH2) lacks a genetic diagnosis due to incomplete USH2A screening in the early days of genetic testing. These cases lack eligibility for optimal genetic counseling and future therapy. USH2A defects are the most frequent cause of USH2 and are also causative in individuals with arRP. Therefore, USH2A is an important target for genetic screening. The aim of this study was to assess unscreened or incompletely screened and unexplained USH2 and arRP cases for (likely) pathogenic USH2A variants. Molecular inversion probe (MIP)-based sequencing was performed for the USH2A exons and their flanking regions, as well as published deep-intronic variants. This was done to identify single nucleotide variants (SNVs) and copy number variants (CNVs) in 29 unscreened or partially pre-screened USH2 and 11 partially pre-screened arRP subjects. In 29 out of these 40 cases, two (likely) pathogenic variants were successfully identified. Four of the identified SNVs and one CNV were novel. One previously identified synonymous variant was demonstrated to affect pre-mRNA splicing. In conclusion, genetic diagnoses were obtained for a majority of cases, which confirms that MIP-based sequencing is an effective screening tool for USH2A. Seven unexplained cases were selected for future analysis with whole genome sequencing.

Reports of Coding-Complete Genome Sequences of Five 2019 Novel Coronavirus (SARS-CoV-2) Strains Isolated in Bangladesh.

This study determined five coding-complete genome sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains isolated from oropharyngeal swab specimens of Bangladeshi patients who were diagnosed with coronavirus disease 2019 (COVID-19) and had no travel history.

Entropy optimized Darcy-Forchheimer nanofluid (Silicon dioxide, Molybdenum disulfide) subject to temperature dependent viscosity.

Background In this research communication, entropy optimized Darcy-Forchheimer flow with magnetohydrodynamic over a stretched surface is considered. Here Molybdenum disulfide (MOS2) and Silicon dioxide (SiO2) are taken as a nanoparticles and Propylene glycol as a continuous phase liquid. Electrically conducting fluid is considered and flow is generated via stretched surface of sheet. The total entropy rate which is depends on four types of irreversibilities i.e., heat transfer, porosity, fluid friction and dissipation) is calculated via second law of thermodynamics. The energy expression is mathematically modeled and discussed subject to heat generation/absorption, dissipation, thermal radiation and Joule heating. Furthermore, temperature dependent viscosity is accounted. Method The nonlinear PDE's (partial differential equations) are first changed to ODE's (ordinary differential equations) through implementation of appropriate similarity variables (transformations). The numerical results of ordinary ones are computed via Built-In-Shooting method. The results for the flow field, temperature, skin friction, Nusselt number and entropy generation are discussed against various sundry flow parameters graphically. Results Salient characteristics of sundry flow parameters on the entropy generation rate, velocity, Bejan number, gradients of velocity, gradient of temperature and temperature are examined and display graphically. The results are computed for both nanoparticles. From obtained results it is observed that temperature field increases versus higher thermal Biot number for both nanoparticles. It is also observed that the thermal field is more in presence of Molybdenum disulfide as compared to Silicon dioxide, because the thermal conductivity of Molybdenum disulfide is higher than Silicon dioxide. Entropy generation and Bejan number show contrast impact versus higher estimations of Brinkman number versus both nanoparticles.

Modeling and computational analysis of 3D radiative stagnation point flow of Darcy-Forchheimer subject to suction/injection.

BACKGROUND: This manuscript elaborates the three-dimensional radiated Darcy-Forchheimer viscous liquid flow subject to permeable stretched surface. The stretched surface is nonlinear and saturated via Darcy-Forchheimer medium. Energy expression is derived through implementation of first of thermodynamics and discussed subject to convective condition and nonlinear heat flux. Mixed convection is also considered. METHOD: The governing systems of nonlinear equations are tackled numerically by Shooting method. RESULTS: Graphical results are depicted and examined with different values of non-dimensional parameters for velocity and energy equations respectively. Drag force and Nusselt number are computationally computed and analyzed through Tables. CONCLUSIONS: It is concluded from the derived outcomes that both component of velocity decay against higher values of local inertia coefficient and inverse Darcy number variables. For suction case both velocities increases while opposite trend is observed for injection case. Temperature profile has an increasing impact for higher values of Radiation, and Biot number while opposite result is seen for injection. Drag force or skin friction declines via larger injection variable. Nusselt number increases for radiation variable.

Spleen tyrosine kinase expression is correlated with human papillomavirus in head and neck cancer.

OBJECTIVES: Spleen tyrosine kinase (SYK) is a promoter of cell survival in a variety of cell types, including normal and cancerous epithelial cells. We hypothesized that SYK would an important therapeutic target to inhibit for the treatment of HNSCC. MATERIALS AND METHODS: SYK protein abundance in patient tumours was evaluated. SYK protein and mRNA abundance was used to examine patient survival and human papillomavirus (HPV) status. Small-interfering RNAs and gene editing with CRISPR/Cas9 were used to evaluate SYK expression on proliferation in HNSCC cell lines. The potency of SYK inhibitor ER27319 maleate on cellular proliferation was tested using a panel of 28 HNSCC cell lines and in vivo in HNSCC patient-derived xenograft (PDX) models. RESULTS: Moderate to high protein expression of SYK was observed in 24% of patient tumors and high SYK expression was exclusively observed in HPV-positive samples (p < 0.001). SYK inhibition with RNA interference, gene editing or a SYK inhibitor (ER27319) decreased cell proliferation and migration. Treatment of PDXs with ER27319 maleate was observed to reduce tumour burden in vivo in two of three models. CONCLUSIONS: HPV-positive HNSCC harbours high SYK protein levels. We demonstrate that proliferation, migration and overall burden of these tumours can be reduced by genetic or pharmacologic inhibition of SYK. Taken together, these data establish SYK as a therapeutic target for HNSCC.

Chromatic Full-Field Stimulus Threshold and Pupillography as Functional Markers for Late-Stage, Early-Onset Retinitis Pigmentosa Caused by CRB1 Mutations.

PURPOSE: Mutations in the CRB1 gene cause early-onset retinal degeneration (EORD). Clinical disease progression markers, such as visual fields or electrophysiology, are not reliably measurable in most patients to follow the retinal function in patients with CRB1-mutations. METHODS: Ten patients (five females, five males; age 22-56 years) with EORD caused by CRB1 mutations were examined in a cross-sectional manner using best corrected visual acuity (BCVA), perimetry, full-field and multifocal electroretinography, full-field stimulus threshold (FST), and pupillography to red and blue light. Disease duration was defined as the difference between the age at the first symptoms to the age at examination in years. RESULTS: BCVA was quantifiable in six patients and ranged from light perception to 20/50. The visual field was measurable only in three patients who had the shortest disease duration. Full-field and multifocal electroretinography were not measurable in any patient. FST to blue and red light were measurable in all patients except the one with the longest disease duration; the thresholds ranged from -16.7 to 1.5 dB for red light and from -40.2 to 2.5 dB for blue light (0 dB = 0.01 cd.s/m2) and showed correlations with disease duration (r = 0.87 for blue, r = 0.65 for red, r = 0.8 for blue-red difference). The maximal relative pupil constriction amplitude (MRA) showed low or no correlations with disease duration (r = -0.55 for blue, r = -0.3 for red light); the blue-red difference in the post-illumination pupil responses (PIPR) showed no correlation with disease duration (r = -0.05). Compared to healthy eyes, the MRA to red and blue light was significantly decreased (P < 0.001) and the blue-red PIPR difference was significantly increased (P = 0.003). CONCLUSIONS: FST features a valid clinical marker in late-stage early-onset retinitis pigmentosa caused by CRB1 mutations correlating with disease duration. This indicates the potential as a progression marker of disease. The pupil responses to full-field chromatic stimuli show significant differences from the normal population: the remaining responses, although reduced, indicate a partially preserved inner retinal function despite severe photoreceptor dysfunction. TRANSLATIONAL RELEVANCE: The functional measurements presented in this study present a valid clinical progression marker in late-stage early onset retinitis pigmentosa caused by biallelic CRB1 mutations. Additionally, they can be used as outcome measures for safety and efficacy in clinical therapy trials.

Theoretical and mathematical analysis of entropy generation in fluid flow subject to aluminum and ethylene glycol nanoparticles.

BACKGROUND: Here we have conducted a magnetohydrodynamic (MHD) flow of viscous material with alumina water and ethylene glycol over a stretched surface. The flow is discussed with and without effective Prandtl number. MHD liquid is considered. Electric field is absent. Effect of uniform magnetic field is taken in the vertical direction to the surface. Influence of thermal radiation as well as Joule heating are taken into account for both aluminum oxide-water and aluminum oxide-Ethylene glycol nanofluids. Velocity slip and melting heat effects are considered. METHODS: The nonlinear flow expressions are numerically solved via ND-solve technique (built-in-Shooting). RESULTS: The physical impacts of flow variables like mixed convection parameter, magnetic parameter, Reynold number, Eckert number, melting parameter and heat source/sink parameter are graphically discussed. Moreover, entropy generation (irreversibility) and Bejan number are discussed graphically through various flow variables. Physical quantities like skin friction coefficient and Sherwood and Nusselt numbers are numerically calculated and discussed through Tables. CONCLUSIONS: Impact of magnetic and slip parameters on the velocity field show decreasing behavior for both effective and without effective Prandtl number. Temperature field increases for both effective and without effective Prandtl number for higher values of magnetic and radiative parameters. Entropy number is an increasing function of Reynolds number while Bejan number shows opposite impact against Reynolds number. Moreover, heat transfer rate upsurges versus larger melting and radiative parameter.

Nanomaterial based flow of Prandtl-Eyring (non-Newtonian) fluid using Brownian and thermophoretic diffusion with entropy generation.

BACKGROUND: The augmentation of cooling or heating in a mechanical and industrial process may create a saving in energy, decrease process time, protract the working existence of hardware and raise thermal rating. A few procedures are even influenced subjectively by the action of increased heat transport. The advancement of high performance thermal frameworks for heat transport augmentation has turned out to be well known these days. Various works has been conducted to gain an understanding of heat transport execution for their viable application to heat transport enhancement. Consequently the appearance of high heat flow procedures has made huge interest for new innovations to increase the heat transport. Therefore, entropy generation in dissipative nanomaterial flow of Prandtl-Eyring nanofluid subject to heated stretchable surface. The impact of zero shear rate viscosity is discussed through Prandtl-Eyring fluid model. Through implementation of thermodynamics second law's total entropy rate is calculated. Heat and mass transfer features are discussed using Brownian diffusion and thermophoresis. Homogeneous and heterogeneous chemical reactions are also accounted. METHODS: Nonlinear partial differential systems are leads to ordinary systems through adequate similarity transformations. The obtained nonlinear ordinary systems are solved by Newton built in shooting technique. RESULTS: Behaviors of different flow parameters on velocity, temperature, entropy generation rate, Bejan number and concentration are graphically discussed. Skin friction coefficient and heat transfer rate are discussed through tables. Entropy generation rate enhances for larger estimation of material parameter and Brinkman number. Bejan number is equal to one when Brinkman number is equal to zero and then progressively decreases for higher values of Brinkman number. CONCLUSIONS: A significant increment has been observed in the velocity field versus material parameter, while opposite trends is noticed forß.Temperature field enhances against higher values of thermophoresis and Brownian parameters while it decays through larger Prandtl number. Mass concentration upsurges versus higher thermophoresis parameter and declined via larger Brownian parameter and homogeneous and heterogeneous parameters. Furthermore, entropy rate and Bejan number show contrast impact versus material parameter and Brinkman number.

Elastic layered rubber-graphene composite fabricated by rubbing-in technology for the multi-functional sensors.

In this work, the elastic layered rubber-graphene composite based multi-functional sensor has been fabricated by rubbing-in technology. The effects of temperature, displacement, pressure and humidity on the impedance of the multi-functional sensor has been investigated in the frequency range of 0-200 kHz. The impedance of the samples decreased under the effect of uniaxial compressive displacement and under the effect of pressure. The temperature coefficient of the samples was found to be -0.836 and -0.862 %/°C with the increase in temperature from 29 °C to 54 °C, respectively, while the impedance of the samples decreased 1.26 ± 0.01 times with the increase in temperature from 29 °C to 54 °C while, respectively. The humidity dependent cross-sensitivity of the samples was investigated in the relative humidity range of (58-93) %RH and no effect of humidity on the performance of the sensor has been observed. The elastic layered rubber-graphene composite potentially can be used as displacement, frequency, temperature and pressure sensors.

Effects of Residual Stress Distribution on Interfacial Adhesion of Magnetron Sputtered AlN and AlN/Al Nanostructured Coatings on a (100) Silicon Substrate.

The present study investigated the influence of nanoscale residual stress depth gradients on the nano-mechanical behavior and adhesion energy of aluminium nitride (AlN) and Al/AlN sputtered thin films on a (100) silicon substrate. By using a focused ion beam (FIB) incremental ring-core method, the residual stress depth gradient was assessed in the films in comparison with standard curvature residual stress measurements. The adhesion energy was then quantified by using a nanoindentation-based model. Results showed that the addition of an aluminum layer gave rise to additional tensile stress at the coating/substrate interface, which can be explained in terms of the differences of thermal expansion coefficients with the silicon substrate. Therefore, the coatings without the Al layer showed better adhesion because of a more homogeneous compressive residual stress in comparison with the coating having the Al layer, even though both groups of coatings were produced under the same bias voltage. Results are discussed, and some general suggestions are made on the correlation between coating/substrate property combinations and the adhesion energy of multilayer stacks. The results suggested that the Al bond layer and inhomogeneous residual stresses negatively affected the adhesion of AlN to a substrate such as silicon.

Phase I of the Surveillance for Enteric Fever in Asia Project (SEAP): An Overview and Lessons Learned.

Objective: The objective of Phase I of the Surveillance for Enteric Fever in Asia Project (SEAP), a multiphase surveillance study characterizing the burden of disease in South Asia, was to inform data collection for prospective surveillance and to capture clinical aspects of disease. Methods: Through a retrospective record review conducted at hospitals in Bangladesh, India, Nepal, and Pakistan, we examined laboratory and clinical records to assess the culture positivity rate for Salmonella Typhi and Salmonella Paratyphi, age and sex distribution, and antimicrobial susceptability in each country. Results: Of all blood cultures performed in Bangladesh, India, Nepal, and Pakistan, 1.5%, 0.43%, 2%, and 1.49%, respectively, were positive for S. Typhi and 0.24%, 0.1%, 0.5%, and 0.67%, respectively, were positive for S. Paratyphi. A higher proportion of laboratory-confirmed infections in Bangladesh and Pakistan were aged ≤5 years, while India and Nepal had a higher proportion of participants aged 15-25 years. In all countries, the sex of the majority of participants was male. The majority of isolates in all countries were resistant to fluoroquinolones, with a high proportion also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Discussion: Enteric fever remains endemic in South Asia. Data generated by this study can help inform strategies for implementation and evaluation of prevention and control measures.

Identification of Inherited Retinal Disease-Associated Genetic Variants in 11 Candidate Genes.

Inherited retinal diseases (IRDs) display an enormous genetic heterogeneity. Whole exome sequencing (WES) recently identified genes that were mutated in a small proportion of IRD cases. Consequently, finding a second case or family carrying pathogenic variants in the same candidate gene often is challenging. In this study, we searched for novel candidate IRD gene-associated variants in isolated IRD families, assessed their causality, and searched for novel genotype-phenotype correlations. Whole exome sequencing was performed in 11 probands affected with IRDs. Homozygosity mapping data was available for five cases. Variants with minor allele frequencies ≤ 0.5% in public databases were selected as candidate disease-causing variants. These variants were ranked based on their: (a) presence in a gene that was previously implicated in IRD; (b) minor allele frequency in the Exome Aggregation Consortium database (ExAC); (c) in silico pathogenicity assessment using the combined annotation dependent depletion (CADD) score; and (d) interaction of the corresponding protein with known IRD-associated proteins. Twelve unique variants were found in 11 different genes in 11 IRD probands. Novel autosomal recessive and dominant inheritance patterns were found for variants in Small Nuclear Ribonucleoprotein U5 Subunit 200 (SNRNP200) and Zinc Finger Protein 513 (ZNF513), respectively. Using our pathogenicity assessment, a variant in DEAH-Box Helicase 32 (DHX32) was the top ranked novel candidate gene to be associated with IRDs, followed by eight medium and lower ranked candidate genes. The identification of candidate disease-associated sequence variants in 11 single families underscores the notion that the previously identified IRD-associated genes collectively carry > 90% of the defects implicated in IRDs. To identify multiple patients or families with variants in the same gene and thereby provide extra proof for pathogenicity, worldwide data sharing is needed.

Barriers to typhoid fever vaccine access in endemic countries.

Typhoid vaccines have been available as a means of disease control and prevention since 1896; however, their use as a routine tool for disease prevention in endemic settings has been hampered because of: 1) insufficient data on disease burden particularly regarding the lack of health care access in the poorest communities affected by typhoid; 2) limitations of the typhoid vaccine, such as shorter duration of protection, moderate efficacy in young children, and no efficacy for infants; 3) inadequate evidence on potential economic benefits when used for a larger population; 4) neglect in favor of alternative interventions that require massive infrastructure; 5) no financial support or commitment regarding vaccine delivery cost; 6) ambivalence about whether to invest in water and sanitation hygiene versus the vaccine; and 7) clarity on global policy for country adoption. If current typhoid-protein conjugate vaccines live up to their promise of higher efficacy, longer duration of protection, and efficacy in young children, typhoid vaccine use will be a critical component of short- and medium-term disease control strategies. Typhoid control could be accelerated if the global framework includes plans for accelerated introduction of the conjugate typhoid vaccine in developing countries.

Effect of nano-hydroxyapatite reinforcement in mechanically alloyed NiTi composites for biomedical implant.

Equi-atomic NiTi alloy composites reinforced with 0, 2, 4 and 6vol.% nano-hydroxyapatite (HA) were successfully synthesized using pressureless sintering. Pure Ni and Ti elements were ball milled for 10h in order to produce a mechanically alloyed equi-atomic NiTi alloy (MA-NiTi). Mechanically alloyed NiTi and HA powders were blended, compacted and then sintered for 3h at 1325K. The sintered density varied inversely with volume percent of HA reinforcement. The X-Ray diffraction spectra and SEM images showed the formation of multiple phases like NiTi, NiTi2, Ni3Ti, and Ni4Ti3. The back scattered-SEM image analysis confirmed the presence of Ni-rich and Ti-rich phases with increasing HA content. The 6vol.% HA reinforced composite showed Ni3Ti as the major phase having the highest hardness value which can be attributed to the presence of relatively harder phases along with higher HA content as a reinforcement. The composite of MA-NiTi with 2vol.% HA manifested the most desirable results in the form of better sintering density mainly due to the minute decomposition of NiTi into other phases. Therefore, the 2vol.% reinforced MA-NiTi composite can be exploited as a novel material for manufacturing biomedical implants.

Nontyphoidal salmonella disease: Current status of vaccine research and development.

Among more than 2500 nontyphoidal Salmonella enterica (NTS) serovars, S. enterica serovar Typhimurium and S. enterica serovar Enteritidis account for approximately fifty percent of all human isolates of NTS reported globally. The global incidence of NTS gastroenteritis in 2010 was estimated to be 93 million cases, approximately 80 million of which were contracted via food-borne transmission. It is estimated that 155,000 deaths resulted from NTS in 2010. NTS also causes severe, extra-intestinal, invasive bacteremia, referred to as invasive nontyphoidal Salmonella (iNTS) disease. iNTS disease usually presents as a febrile illness, frequently without gastrointestinal symptoms, in both adults and children. Symptoms of iNTS are similar to malaria, often including fever (>90%) and splenomegaly (>40%). The underlying reasons for the high rates of iNTS disease in Africa are still being elucidated. Evidence from animal and human studies supports the feasibility of developing a safe and effective vaccine against iNTS. Both antibodies and complement can kill Salmonella species in vitro. Proof-of-principle studies in animal models have demonstrated efficacy for live attenuated and subunit vaccines that target the O-antigens, flagellin proteins, and other outer membrane proteins of serovars Typhimurium and Enteritidis. More recently, a novel delivery strategy for NTS vaccines has been developed: the Generalized Modules for Membrane Antigens (GMMA) technology which presents surface polysaccharides and outer membrane proteins in their native conformation. GMMA technology is self-adjuvanting, as it delivers multiple pathogen-associated molecular pattern molecules. GMMA may be particularly relevant for low- and middle-income countries as it has the potential for high immunologic potency at a low cost and involves a relatively simple production process without the need for complex conjugation. Several vaccines for the predominant NTS serovars Typhimurium and Enteritidis, are currently under development.

Status of paratyphoid fever vaccine research and development.

Salmonella enterica serovars Typhi and Paratyphi (S. Paratyphi) A and B cause enteric fever in humans. Of the paratyphoid group, S. Paratyphi A is the most common serovar. In 2000, there were an estimated 5.4 million cases of S. Paratyphi A worldwide. More recently paratyphoid fever has accounted for an increasing fraction of all cases of enteric fever. Although vaccines for typhoid fever have been developed and in use for decades, vaccines for paratyphoid fever have not yet been licensed. Several S. Paratyphi A vaccines, however, are in development and based on either whole cell live-attenuated strains or repeating units of the lipopolysaccharide O-antigen (O:2) conjugated to different protein carriers. An O-specific polysaccharide (O:2) of S. Paratyphi A conjugated to tetanus toxoid (O:2-TT), for example, has been determined to be safe and immunogenic after one dose in Phase I and Phase II trials. Two other conjugated vaccine candidates linked to diphtheria toxin and a live-attenuated oral vaccine candidate are currently in preclinical development. As promising vaccine candidates are advanced along the development pipeline, an adequate supply of vaccines will need to be ensured to meet growing demand, particularly in the most affected countries.