The effect of Turbulence Models on Numerical Prediction of Air Flow within Street Canyons

November 15-17, Belgrad

Borna disease virus infects human neural progenitor cells and impairs neurogenesis.

Understanding the complex mechanisms by which infectious agents can disrupt behavior represents a major challenge. The Borna disease virus (BDV), a potential human pathogen, provides a unique model to study such mechanisms. Because BDV induces neurodegeneration in brain areas that are still undergoing maturation at the time of infection, we tested the hypothesis that BDV interferes with neurogenesis. We showed that human neural stem/progenitor cells are highly permissive to BDV, although infection does not alter their survival or undifferentiated phenotype. In contrast, upon the induction of differentiation, BDV is capable of severely impairing neurogenesis by interfering with the survival of newly generated neurons. Such impairment was specific to neurogenesis, since astrogliogenesis was unaltered. In conclusion, we demonstrate a new mechanism by which BDV might impair neural function and brain plasticity in infected individuals. These results may contribute to a better understanding of behavioral disorders associated with BDV infection

Key Features Relevant to Select Antigens and TCR From the MHC-Mismatched Repertoire to Treat Cancer

Adoptive transfer of T cells transgenic for tumor-reactive T-cell receptors (TCR) is an attractive immunotherapeutic approach. However, clinical translation is so far limited due to challenges in the identification of suitable target antigens as well as TCRs that are concurrent safe and efficient. Definition of key characteristics relevant for effective and specific tumor rejection is essential to improve current TCR-based adoptive T-cell immunotherapies. We here characterized in-depth two TCRs derived from the human leukocyte antigen (HLA)-mismatched allogeneic repertoire targeting two different myeloperoxidase (MPO)-derived peptides presented by the same HLA-restriction element side by side comprising state of the art biochemical and cellular in vitro, in vivo, and in silico experiments. In vitro experiments reveal comparable functional avidities, off-rates, and cytotoxic activities for both TCRs. However, we observed differences especially with respect to cytokine secretion and cross-reactivity as well as in vivo activity. Biochemical and in silico analyses demonstrate different binding qualities of MPO-peptides to the HLA-complex determining TCR qualities. We conclude from our biochemical and in silico analyses of peptide-HLA-binding that rigid and high-affinity binding of peptides is one of the most important factors for isolation of TCRs with high specificity and tumor rejection capacity from the MHC-mismatched repertoire. Based on our results, we developed a workflow for selection of such TCRs with high potency and safety profile suitable for clinical translation

Taking a Proposal Seriously : Orientations to Agenda and Agency in Support Workers’ Responses to Client Proposals

While joint decision-making is regularly launched by a proposal, it is the recipients’ responses that crucially influence the proposal outcome. This chapter examines how support workers respond to the proposals made by clients during rehabilitation group meetings at the Clubhouse. Drawing on a collection of 180 client-initiated proposal sequences, the paper describes two dilemmas that the support workers face when seeking to take client proposals “seriously.” The first concerns the meeting’s agenda and consists of a tension between providing recognition for the individual client and encouraging collective participation. The second dilemma has to do with agency and consists of a tension between focusing on the client as the originator of the proposal and avoiding treating him or her alone accountable for it. The analysis of these dilemmas contributes to a deeper understanding of group decision-making, in general, while these findings have specific relevance in mental health rehabilitation.While joint decision-making is regularly launched by a proposal, it is the recipients’ responses that crucially influence the proposal outcome. This chapter examines how support workers respond to the proposals made by clients during rehabilitation group meetings at the Clubhouse. Drawing on a collection of 180 client-initiated proposal sequences, the paper describes two dilemmas that the support workers face when seeking to take client proposals “seriously.” The first concerns the meeting’s agenda and consists of a tension between providing recognition for the individual client and encouraging collective participation. The second dilemma has to do with agency and consists of a tension between focusing on the client as the originator of the proposal and avoiding treating him or her alone accountable for it. The analysis of these dilemmas contributes to a deeper understanding of group decision-making, in general, while these findings have specific relevance in mental health rehabilitation.Peer reviewe

Sediment and mercury distribution in the Dow Wetlands, San Francisco Bay-Delta

The main goal of this study was to assess distribution of sediment sizes and mercury concentrations in the vicinity of Dow Wetlands area and to correlate distribution of sediment sizes and mercury concentrations to different types of depositional environments in this area. The area of study is located to the north of the town of Antioch. Sediment samples were collected from the following sites in the Bay Delta: Dow Wetlands, Brown Island, Sherman Island, Antioch Marina, and Big Break Bay. Sampling was performed in August 2003 and November 2004. Sediment samples were collected both from shore and from a boat using handheld coring devices and an Eckman grab sampler from the upper 10 cm of sediments. The grain size analyses were performed at Moss Landing Marine Laboratory using a laser diffraction grain size analyzer Beckman Coulter Model LS 13 320, and by pipette method at the Department of Geological Sciences at California State University East Bay. The grain size distribution was related to distribution of total mercury concentration. The statistical parameters (mean size, standard deviation, skewness, and kurtosis) were calculated using the method of moment. The samples show characteristics of multi-source (poorly sorted) sediments with pronounced skewness and kurtosis, or large deviation from normal distribution curves. The curves derived from grain size distributions are bimodal to polymodal, which could mean that samples consist of two or more subpopulations with different means and standard deviations. The average size of all samples is approximately 103 μm, which is in the range of very fine sand. The majority of samples are extremely leptokurtic and strongly fine skewed. They have peaks of values within the range of fine sand or coarse silt with significant amounts of fines (silt and clay). The data suggest that samples with larger specific surface areas have higher mercury concentrations due to the increased amount of fine fractions, particularly clay. The average mercury concentration at the area of study is 385 ppb. The highest concentration of mercury occurred in the Dow Wetlands at location S-30 (1929 ppb), which exceeds the Total Maximum Daily Load target for mercury in sediments by almost 10 times. There are three different depositional types of environments in the area of study: the open channel (sandy bottoms with traces of fines and low mercury concentrations), stream banks (sandy and silty bottoms with more clay and higher mercury concentrations), and enclosed areas with low current velocities (dominant fine fractions, particularly clay, and highest mercury concentrations). In general, the data suggest that mercury concentrations are higher in areas with denser vegetation, low water currents, dominant fine sediment fractions, and away from open water

Maternal psychological distress in primary care and association with child behavioural outcomes at age three

Observational studies indicate children whose mothers have poor mental health are at increased risk of socio-emotional behavioural difficulties, but it is unknown whether these outcomes vary by the mothers’ mental health recognition and treatment status. To examine this question, we analysed linked longitudinal primary care and research data from 1078 women enrolled in the Born in Bradford cohort. A latent class analysis of treatment status and self-reported distress broadly categorised women as (a) not having a common mental disorder (CMD) that persisted through pregnancy and the first 2 years after delivery (N = 756, 70.1 %), (b) treated for CMD (N = 67, 6.2 %), or (c) untreated (N = 255, 23.7 %). Compared to children of mothers without CMD, 3-year-old children with mothers classified as having untreated CMD had higher standardised factor scores on the Strengths and Difficulties Questionnaire (d = 0.32), as did children with mothers classified as having treated CMD (d = 0.27). Results were only slightly attenuated in adjusted analyses. Children of mothers with CMD may be at risk for socio-emotional and behavioural difficulties. The development of effective treatments for CMD needs to be balanced by greater attempts to identify and treat women. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00787-015-0777-2) contains supplementary material, which is available to authorized users

Dynamical model of antibiotic responses linking expression of resistance genes to metabolism explains emergence of heterogeneity during drug exposures

Antibiotic responses in bacteria are highly dynamic and heterogeneous, with sudden exposure of bacterial colonies to high drug doses resulting in the coexistence of recovered and arrested cells. The dynamics of the response is determined by regulatory circuits controlling the expression of resistance genes, which are in turn modulated by the drug's action on cell growth and metabolism. Despite advances in understanding gene regulation at the molecular level, we still lack a framework to describe how feedback mechanisms resulting from the interdependence between expression of resistance and cell metabolism can amplify naturally occurring noise and create heterogeneity at the population level. To understand how this interplay affects cell survival upon exposure, we constructed a mathematical model of the dynamics of antibiotic responses that links metabolism and regulation of gene expression, based on the tetracycline resistance tet operon in E. coli. We use this model to interpret measurements of growth and expression of resistance in microfluidic experiments, both in single cells and in biofilms. We also implemented a stochastic model of the drug response, to show that exposure to high drug levels results in large variations of recovery times and heterogeneity at the population level. We show that stochasticity is important to determine how nutrient quality affects cell survival during exposure to high drug concentrations. A quantitative description of how microbes respond to antibiotics in dynamical environments is crucial to understand population-level behaviors such as biofilms and pathogenesis

Detection and analysis of new psittacine beak and feather disease virus (PBFDv) nucleotide sequences

ΔΕΝ ΥΠΑΡΧΕΙ ΠΕΡΙΛΗΨΗPsittacine beak and feather disease (PBFD) affects a large number of Psittaciformes species. In this study, five White Cockatoo parrots (Cacatua alba) with clinical signs of PBFD were examined. After euthanasia, a full necropsy of parrots was performed and organs with macroscopic changes were sampled for routine histopathological evaluation. To confirm the presence of psittacine beak and feather disease virus (PBFDv), feather samples were analyzed with the PCR method. Sequence analysis of the obtained PCR products indicated their close relationship (99%) to other PBFDv isolates. Six variable nucleotide sites were discovered, two missense and four silent mutations. This paper presents the evidence of new PBFDv sequence in Cockatoo species