Abstract
Intense particle beams generated from the interaction of ultrahigh intensity lasers with sample foils provide options in radiography, high-yield neutron sources, high-energy-density-matter ...generation, and ion fast ignition. An accurate understanding of beam transportation behavior in dense matter is crucial for all these applications. Here we report the experimental evidence on one order of magnitude enhancement of intense laser-accelerated proton beam stopping in dense ionized matter, in comparison with the current-widely used models describing individual ion stopping in matter. Supported by particle-in-cell (PIC) simulations, we attribute the enhancement to the strong decelerating electric field approaching 1 GV/m that can be created by the beam-driven return current. This collective effect plays the dominant role in the stopping of laser-accelerated intense proton beams in dense ionized matter. This finding is essential for the optimum design of ion driven fast ignition and inertial confinement fusion.
Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial ...side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal epithelial surfaces. We report here the first receptor for the cell wall glycopolymer WTA on nasal epithelial cells. In several assay systems this type F-scavenger receptor, termed SREC-I, bound WTA in a charge dependent manner and mediated adhesion to nasal epithelial cells in vitro. The impact of WTA and SREC-I interaction on epithelial adhesion was especially pronounced under shear stress, which resembles the conditions found in the nasal cavity. Most importantly, we demonstrate here a key role of the WTA-receptor interaction in a cotton rat model of nasal colonization. When we inhibited WTA mediated adhesion with a SREC-I antibody, nasal colonization in the animal model was strongly reduced at the early onset of colonization. More importantly, colonization stayed low over an extended period of 6 days. Therefore we propose targeting of this glycopolymer-receptor interaction as a novel strategy to prevent or control S. aureus nasal colonization.
Zika virus (ZIKV) is a re-emerging flavivirus that has caused large-scale epidemics. Infection during pregnancy can lead to neurologic developmental abnormalities in children. There is no approved ...vaccine or therapy for ZIKV. To uncover cellular pathways required for ZIKV that can be therapeutically targeted, we transcriptionally upregulated all known human coding genes with an engineered CRISPR-Cas9 activation complex in human fibroblasts deficient in interferon (IFN) signaling. We identified Ras homolog family member V (
) and WW domain-containing transcription regulator 1 (
) as proviral factors, and found them to play important roles during early ZIKV infection in A549 cells. We then focused on RhoV, a Rho GTPase with atypical terminal sequences and membrane association, and validated its proviral effects on ZIKV infection and virion production in SNB-19 cells. We found that RhoV promotes infection of some flaviviruses and acts at the step of viral entry. Furthermore, RhoV proviral effects depend on the complete GTPase cycle. By depleting Rho GTPases and related proteins, we identified RhoB and Pak1 as additional proviral factors. Taken together, these results highlight the positive role of RhoV in ZIKV infection and confirm CRISPR activation as a relevant method to identify novel host-pathogen interactions.
Objective
To systematically explore the outcomes of Independent Housing and Support (IHS) for people with severe mental disorders when compared to other residential settings.
Method
Systematic review ...of Randomised and Non‐Randomised Controlled Trials of publications that analyse the outcomes of living in independent settings versus institutionalised accommodation. Risk of bias assessment was adapted from the Cochrane Collaboration's ACROBAT‐Tool. The analysis was conducted separately for publications with homeless and non‐homeless people.
Results
Twenty‐four publications from studies with homeless people and eight publications from studies with non‐homeless people were included. Risk of bias was much lower in studies with the homeless. No RCT was found in the sample of publications with the non‐homeless. Overall, results from Independent Housing and Support‐settings are not inferior to results from institutionalised settings.
Conclusion
The results indicate that Independent Housing and Support‐settings provide at least similar outcomes than residential care. We propose that clients’ preferences should determine the choice of housing setting.
We report on a precision energy loss measurement and theoretical investigation of 100 keV/u helium ions in a hydrogen-discharge plasma. Collision processes of helium ions with protons, free ...electrons, and hydrogen atoms are ideally suited for benchmarking plasma stopping-power models. Energy loss results of our experiments are significantly higher than the predictions of traditional effective charge models. We obtained good agreement with our data by solving rate equations, where in addition to the ground state, also excited electronic configurations were considered for the projectile ions. Hence, we demonstrate that excited projectile states, resulting from collisions, leading to capture-, ionization-, and radiative-decay processes, play an important role in the stopping process in plasma.
Interferon-stimulated genes (ISGs) form the backbone of the innate immune system and are important for limiting intra- and intercellular viral replication and spread. We conducted a ...mass-spectrometry-based survey to understand the fundamental organization of the innate immune system and to explore the molecular functions of individual ISGs. We identified interactions between 104 ISGs and 1,401 cellular binding partners engaging in 2,734 high-confidence interactions. 90% of these interactions are unreported so far, and our survey therefore illuminates a far wider activity spectrum of ISGs than is currently known. Integration of the resulting ISG-interaction network with published datasets and functional studies allowed us to identify regulators of immunity and processes related to the immune system. Given the extraordinary robustness of the innate immune system, this ISG network may serve as a blueprint for therapeutic targeting of cellular systems to efficiently fight viral infections.
An obituary for Vincent Clifford Moran, who died on Aug 30, 2023, is presented. After completing his MSc, Cliff was appointed as a Lecturer in Zoology at Rhodes, with promotions to Senior Lecturer, ...Associate Professor and, in 1979, Professor of Entomology, a position he retained until 1985. He also served as Dean of the Faculty of Science at Rhodes from 1983 to 1985 and was elected to the Rhodes University Council from 1984 to 1985. In 1986, he moved to the University of Cape Town (UCT) where he served as Dean of the Faculty of Science, a permanent, full-time appointment he held until 1998. He was also elected to the University of Cape Town's Council from 1987 to 1995. He retired in 1999, becoming Professor Emeritus and a Research Fellow at UCT. In his early career, Cliff excelled as a lecturer and inspired many young undergraduate and postgraduate students to pursue careers in entomology. He also became a diligent administrator and was widely appreciated for his fairness and untiring efforts to facilitate and improve the working environment for all.
Aim Geologically dynamic areas often harbour remarkable levels of biodiversity. Among other factors, mountain building is assumed to be a precondition for species radiation, and yet, the potential ...role of immigration as a source of biodiversity prior to radiation is often neglected. Here, we studied the biogeographical history of the large genus Saxifraga to unravel the role played by the Qinghai-Tibet Plateau (QTP) for the diversification of this genus and to understand factors that have led to the establishment of high biodiversity in and around this region. Location QTP and surrounding mountain ranges and worldwide distribution range of Saxifraga. Methods Using a total of 420 taxa (321 ingroup taxa) comprising more than 60% of extant Saxifraga species, we studied the evolutionary history of Saxifraga by performing phylogenetic analyses (maximum likelihood and Bayesian inference on nuclear ITS and plastid trnL-trnV, matK sequences), divergence time estimation (using uncorrelated log-normal clock models and four fossil constraints in beast) and ancestral range estimation (using BioGeoBEARS). Results Saxifraga originated in North America around 74 (64–83) Ma, dispersed to South America and northern Asia during its early diversification and colonized Europe and the QTP region by the Late Eocene. The QTP region was colonized several times independently, followed in some lineages by rapid radiations, temporally coinciding with recent uplifts of the Hengduan Mountains at the southeastern fringe of the QTP. Subsequently, several lineages dispersed out of Tibet. Main conclusions Immigration, recent rapid radiation and lineage persistence were all important processes for the establishment of a rich species stock of Saxifraga in the QTP region. Because floristic exchanges between the neighbouring areas and the QTP region were bi-directional, the spatio-temporal evolution of Saxifraga contrasts with the 'out of QTP' pattern, which has often been assumed for northern temperate plants.
People with severe mental illness (SMI) have a high risk of living socially excluded from the mainstream society. Policy initiatives and health systems aim to improve the social situation of people ...who suffer from mental health disabilities. The aim of this study was to explore the extent of social exclusion (employment and income, social network and social activities, health problems) of people with SMI in Switzerland.
Data from the Swiss Health Survey 2012 were used to compare the social exclusion magnitude of people with SMI with those suffering from severe physical illness, common mental illness and the general population.
With the exception of Instrumental Activities of Daily Living, we found a gradient of social exclusion that showed people with SMI to be more excluded than the comparison groups. Loneliness and poverty were widespread among people with SMI. Logistic regression analyses on each individual exclusion indicator revealed that people with SMI and people with severe physical illness were similarly excluded on many indicators, whereas people with common mental illness and the general population were much more socially included.
In contrast to political and health system goals, many people with SMI suffer from social exclusion. Social policy and clinical support should increase the efforts to counter exclusionary trends, especially in terms of loneliness and poverty.
To facilitate the development of therapies for rheumatoid arthritis (RA), the Innovative Medicines Initiative BTCure has combined the experience from several laboratories worldwide to establish a ...series of protocols for different animal models of arthritis that reflect the pathogenesis of RA. Here, we describe chronic pristane-induced arthritis (PIA) model in DA rats, and provide detailed instructions to set up and evaluate the model and for reporting data.
We optimized dose of pristane and immunization procedures and determined the effect of age, gender, and housing conditions. We further assessed cage-effects, reproducibility, and frequency of chronic arthritis, disease markers, and efficacy of standard and novel therapies.
Out of 271 rats, 99.6% developed arthritis after pristane-administration. Mean values for day of onset, day of maximum arthritis severity and maximum clinical scores were 11.8±2.0 days, 20.3±5.1 days and 34.2±11 points on a 60-point scale, respectively. The mean frequency of chronic arthritis was 86% but approached 100% in long-term experiments over 110 days. Pristane was arthritogenic even at 5 microliters dose but needed to be administrated intradermally to induce robust disease with minimal variation. The development of arthritis was age-dependent but independent of gender and whether the rats were housed in conventional or barrier facilities. PIA correlated well with weight loss and acute phase reactants, and was ameliorated by etanercept, dexamethasone, cyclosporine A and fingolimod treatment.
PIA has high incidence and excellent reproducibility. The chronic relapsing-remitting disease and limited systemic manifestations make it more suitable than adjuvant arthritis for long-term studies of joint-inflammation and screening and validation of new therapeutics.
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