Optimality of mutation and selection in germinal centers

The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ~100-fold affinity improvements, the number of mutations, the hypermutation rate, and the "all or none" phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understandings to the functions of germinal centers.Comment: 5 figures in main text, and 4 figures in Supplementary Informatio

A review of tennis racket performance parameters

The application of advanced engineering to tennis racket design has influenced the nature of the sport. As a result, the International Tennis Federation has established rules to limit performance, with the aim of protecting the nature of the game. This paper illustrates how changes to the racket affect the player-racket system. The review integrates engineering and biomechanical issues related to tennis racket performance, covering the biomechanical characteristics of tennis strokes, tennis racket performance, the effect of racket parameters on ball rebound and biomechanical interactions. Racket properties influence the rebound of the ball. Ball rebound speed increases with frame stiffness and as string tension decreases. Reducing inter-string contacting forces increases rebound topspin. Historical trends and predictive modelling indicate swingweights of around 0.030–0.035 kg/m2 are best for high ball speed and accuracy. To fully understand the effect of their design changes, engineers should use impact conditions in their experiments, or models, which reflect those of actual tennis strokes. Sports engineers, therefore, benefit from working closely with biomechanists to ensure realistic impact conditions

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Sensible heat has significantly affected the global hydrological cycle over the historical period

Globally, latent heating associated with a change in precipitation is balanced by changes to atmospheric radiative cooling and sensible heat fluxes. Both components can be altered by climate forcing mechanisms and through climate feedbacks, but the impacts of climate forcing and feedbacks on sensible heat fluxes have received much less attention. Here we show, using a range of climate modelling results, that changes in sensible heat are the dominant contributor to the present global-mean precipitation change since preindustrial time, because the radiative impact of forcings and feedbacks approximately compensate. The model results show a dissimilar influence on sensible heat and precipitation from various drivers of climate change. Due to its strong atmospheric absorption, black carbon is found to influence the sensible heat very differently compared to other aerosols and greenhouse gases. Our results indicate that this is likely caused by differences in the impact on the lower tropospheric stability

The potential of low-cost ROV for use in deep-sea mineral, ore prospecting and monitoring

With the development of ever more powerful micro-computers, the cost and capabilities of robotic systems for environmental surveying using remotely control systems continues to decrease and improve. Historically, submarine exploration was restricted to companies or organisations with considerable finances and resources; however, the last decade has seen the advent of ‘low cost’ remotely operated vehicles (ROV). These cost anywhere from $400-$40,000 and provide an opportunity for wider participation in ocean exploration. However, with 60% of the world's seafloor lying at depths in excess of 1000 m and current low cost ROVs typiclly depth limited to just 100 m, there is presently an inability to “go deep” affordably. This review assesses the state of the art for deep ROV technologies and identifies the primary technological hurdles to overcome in order to facilitate proliferation of low cost ROVs for deep ocean exploration with an emphasis on their application to mineral and ore prospecting

Adolescents' self-efficacy and digital health literacy: a cross-sectional mixed methods study.

BACKGROUND: The internet and social media are increasingly popular sources of health information for adolescents. Using online health information requires digital health literacy, consisting of literacy, analytical skills and personal capabilities such as self-efficacy. Appraising trustworthiness and relevance of online health information requires critical health literacy to discriminate between sources, critically analyse meaning and relevance, and use information for personal health. Adolescents with poor digital health literacy risk using misinformation, with potential negative health outcomes. We aimed to understand adolescents' contemporary digital health literacy and compared self-efficacy with capability. METHODS: Adolescents (12-17 years) completed an eHEALS self-report digital health literacy measure, a practical search task using a think-aloud protocol and an interview to capture perceived and actual digital health literacy. eHEALS scores were generated using descriptive statistics, search tasks were analysed using an observation checklist and interviews were thematically analysed based on Social Cognitive Theory, focussing on self-efficacy. RESULTS: Twenty-one participants generally had high self-efficacy using online health information but perceived their digital health literacy to be higher than demonstrated. They accessed online health information unintentionally on social media and intentionally via search engines. They appraised information medium, source and content using general internet searching heuristics taught at school. Information on social media was considered less trustworthy than websites, but participants used similar appraisal strategies for both; some search/appraisal heuristics were insufficiently nuanced for digital health information, sometimes resulting in misplaced trust or diminished self-efficacy. Participants felt anxious or relieved after finding online health information, depending on content, understanding and satisfaction. They did not act on information without parental and/or health professional advice. They rarely discussed findings with health professionals but would welcome discussions and learning how to find and appraise online health information. CONCLUSIONS: Whilst adolescents possess many important digital health literacy skills and generally feel self-efficacious in using them, their critical health literacy needs improving. Adolescents desire increased digital health literacy so they can confidently appraise health information they find online and on social media. Co-designed educational interventions with adolescents and health providers are required

Reduced Amygdala and Ventral Striatal Activity to Happy Faces in PTSD Is Associated with Emotional Numbing

There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1) individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2) that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral) faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing

A Review of Current Coral Monitoring Tools/ Diagnostic Methods & Introducing a New Tool to the Coral Health Toolkit

Rapidly and repeatedly ascertaining the health status of coral reefs is an ever more pressing issue as part of activities to understand and monitor the damaging impacts of climate change. A combination of increasing ocean temperatures, acidity and frequency of extreme storm events continues to alter the marine environment beyond what sensitive organisms, such as coral, can cope with. It is therefore vital to establish technologies and validated methods to provide a metric or indication into the health of these organisms. There are currently many surveys and techniques used by coral scientists to uncover insights into the status and assessment of coral reefs, from colour wheels to multispectral satellite surveys. Here we outline an array of current techniques and methods focused specifically on coral monitoring and health diagnosis, ranging across the length scales from simple diver-based surveyance to satellite remote sensing. The technique of using hyperspectral fluorescence imaging is also introduced as a viable novel addition to aid and extend the current toolbox of available technologie

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications