Impaired antibody-mediated protection and defective IgA B cell memory in experimental infection of adults with respiratory syncytial virus

Rationale: Despite relative antigenic stability, respiratory syncytial virus (RSV) re-infects throughout life. After >40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection. Objectives: Characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development. Methods: We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B cell frequencies and antibody longevity. Measurements and Main Results: Despite moderately high levels of pre-existing serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from PCR-confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects, but correlated with plasmablasts that peaked around day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, where virus-specific IgA memory B cells were readily recovered. Conclusions: This observed specific defect in IgA memory may partly explain RSV's ability to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone

Impaired antibody-mediated protection and defective IgA B cell memory in experimental infection of adults with respiratory syncytial virus

Rationale: Despite relative antigenic stability, respiratory syncytial virus (RSV) re-infects throughout life. After >40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection. Objectives: Characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development. Methods: We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B cell frequencies and antibody longevity. Measurements and Main Results: Despite moderately high levels of pre-existing serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from PCR-confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects, but correlated with plasmablasts that peaked around day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, where virus-specific IgA memory B cells were readily recovered. Conclusions: This observed specific defect in IgA memory may partly explain RSV's ability to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone

مشكلات تدريس اللغة العربية في المدرسة الثانوية الإسلامية الحكومية مالكاجي منطقة غووا

ويلاخص الباحث انطلاقا من التفصيلات السابقة، كنتيجة من البحث العلمي، لاخص الباحث عدة المعلومات التالية : 1.أن المشكلة التي واجهها مدرسون, ومن جانب آخر أن الحصة لتعليم العربية حصتان في الأسبوع فقط ، وهناك مدرس اللغة العربية واحد فقط 2.أن عملية تدريس اللغة العربية تمشي بسبب جهد مدرس مادة اللغة العربية في أداء واجبهم كمدرس ومرب. 3.العمليات التي قام بها مدرسو اللغة العربية في مكافحة المشكلات في عملية تدريس اللغة العربية هي ترقية جودة المدرسين، ومحاولة زيادةعدد المدرسين

A Comparative Study of Li-ion Battery Models and Nonlinear Dual Estimation Strategies

Due to their high energy density, durability, low cost, and inherent safety, lithium-ion (Li-ion) batteries are quickly becoming the most popular energy storage method for electric vehicles. Difficulty arises in properly modeling these types of batteries due to a large number of parameters and different architectures. This paper looks at studying six different Li-ion battery models found in literature, and compares their relative performance based on a benchmark dataset. Kalman-based filtering strategies are also employed to estimate important battery parameters such as capacitance, hysteresis, and state of charge (SOC). In addition, the relatively new smooth variable structure filter (SVSF) is used and compared with these Kalman-based strategies. © 2012 IEEE

RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection

In animal models, resident memory CD8+ T (Trm) cells assist in respiratory virus elimination but their importance in man has not been determined. Here, using experimental human respiratory syncytial virus (RSV) infection, we investigate systemic and local virus-specific CD8+ T cell responses in adult volunteers. Having defined the immunodominance hierarchy, we analyze phenotype and function longitudinally in blood and by serial bronchoscopy. Despite rapid clinical recovery, we note surprisingly extensive lower airway inflammation with persistent viral antigen and cellular infiltrates. Pulmonary virus-specific CD8+ T cells display a CD69+CD103+ Trm phenotype and accumulate to strikingly high frequencies into convalescence without continued proliferation. These are more highly differentiated but express fewer cytotoxicity markers than in blood, but their abundance prior to infection correlates with protection from more severe disease

Sustainable and inclusive demand-side resilience: a semi-dynamic model for outage costs

The power system is primarily designed and concerned with supplying electricity to its customers at all times. Nevertheless, power outages are inevitable; therefore, one of the challenges is to accurately determine the costs and damages to consumers in a fair and inclusive manner. Outage events are regularly costed based on a parameter called the Value of Lost Load (VoLL/VOLL). Although some of the influencing factors on outage costs have been identified in the literature, the exact determination of the damage to customers is still considered a big challenge. This work is an effort toward a more sustainable and inclusive demand-side resilience that provides a semi-dynamic model for the assignment of the power outage damage costs to the customers. The results of the proposed method show how using a semi-dynamic model for outage costs leads to more sustainable and inclusive operating decisions in the power system while also leads to a fairer allocation of costs

Approaches towards expression profiling the response to treatment

Over the past 8 years there has been a wealth of breast cancer gene expression studies. The majority of these studies have focused upon characterising a tumour at presentation, before treatment, rather than looking at the effects of treatment on the tumour. More recently, a number of groups have moved from predicting prognosis based upon long-term follow-up to alternative approaches of using expression profiling to measure the effect of treatment on breast tumours and potentially predict response to therapy using either post-treatment samples or both pre-treatment and post-treatment samples. Whilst this provides great potential to further our understanding of the mode of action of treatments and to more accurately select which patients will benefit from a particular treatment, serious issues of experimental design must be considered

Resilience of the respiratory microbiome in controlled adult RSV challenge study

This study of healthy adults revealed no major changes in the bacterial community of the respiratory tracts following RSV inoculation, suggesting that the adult respiratory microbial community is resilient to viral perturbations https://bit.ly/3AwnMc

Resveratrol attenuates hepatic oxidative stress and preserves gut mucosal integrity in high-fat diet-fed rats by modulating antioxidant and anti-inflammatory pathways

This study evaluated the protective effects of resveratrol against high-fat diet (HFD)-induced hepatic dysfunction and intestinal mucus layer depletion with a focus on antioxidant and anti-inflammatory mechanisms. HFD-fed rats were treated with resveratrol for eight weeks, and various metabolic, molecular, and histological parameters were assessed. Resveratrol therapy significantly reduced body weight gain and adiposity, lowered plasma and hepatic oxidative stress markers, and restored endogenous antioxidant enzyme activity. Liver function markers including ALT, AST, and ALP were normalized in treated animals. RT-PCR analysis showed enhanced expression of lipid-metabolizing and antioxidant genes including PPARα, CPT-1, Nrf2, and HO-1. Histological analysis revealed that resveratrol attenuated hepatic steatosis, collagen deposition, and fibrosis. Importantly, it preserved the goblet cell population within both intestinal crypts and villi, thereby maintaining the integrity of the gut-mucus barrier. These findings demonstrate that resveratrol exerts a multi-organ protective effect by simultaneously preserving intestinal mucus, improving hepatic antioxidant defenses, and reducing fibrosis. This study highlights a novel gut–liver axis mechanism for resveratrol action that extends beyond its well-known anti-obesity and mitochondrial benefits