Regulation of B cell fate by chronic activity of the IgE B cell receptor.

IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE+ B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help. This antigen-independent PC differentiation involved multiple IgE domains and Syk, CD19, BLNK, Btk, and IRF4. Disruption of BCR signaling in mice led to consistently exaggerated IgE+ germinal center (GC) B cell but variably increased PC responses. We were unable to confirm reports that the IgE BCR directly promoted intrinsic apoptosis. Instead, IgE+ GC B cells exhibited poor antigen presentation and prolonged cell cycles, suggesting reduced competition for T cell help. We propose that chronic BCR activity and access to T cell help play critical roles in regulating IgE responses

The Relationship between Information Systems (IS) Assets, Organizational Capabilities, and IS-enabled Absorptive Capacity in U.S. State Information Technology Departments

Despite the recognition that information is a strategic asset for any state government, we lack research on the deployment and use of information systems in the U.S. state government context. Information systems are central for state agencies’ efforts to develop optimal responses to demands from their internal and external constituents. We examine how a specific IS asset combines with prior knowledge to influence organizational capabilities. We also examine the connection between organizational capabilities and the IS-enabled absorptive capacity of U.S. state IT departments from the perspective of IS employees. This study may help researchers and practitioners understand the role of IS assets in forming IS-enabled absorptive capacity in government organizations. We collected survey data from 417 government IS employees that represented 21 different states. The findings indicate that the role of an IS asset depends on the type of asset. Inside-out IS assets (ERP) moderate the relationship between prior knowledge and organizational capabilities, while outside-in IS assets (CRM) directly affect organizational capabilities. In addition, organizational capabilities can directly affect IS-enabled absorptive capacity in IT departments. This research increases our understanding of the influence of different IS assets on IS-enabled absorptive capacity in state government IT departments. We discuss limitations and directions for future research

How Managers and Workers See Their World: Perceptions of the Relationship Between Organizational Capabilities and Absorptive Capacity in U.S. State Information Systems Departments

Despite the recognition that information is a strategic asset to any state government, there is a relative dearth of research on the information systems (IS) function in state government. This stands in contrast to the number of articles devoted to e-government initiatives. IS departments however are central to state agencies’ efforts to develop optimal responses to demands from their internal and external constituents. The authors examine the connections between perceptions of critical agency capabilities (socialization, coordination, and systems) and the absorptive capacity of state IS departments from the perspective of IS workers and IS managers. Findings indicate that two critical capabilities (socialization and coordination) explained 62.5% of the variation in absorptive capacity for IS workers and 47% of the variation for IS managers. In addition, the influence of the relevant knowledge of IS workers and managers is found to have differing influences on agency capabilities

The HIV Genomic Incidence Assay Meets False Recency Rate and Mean Duration of Recency Infection Performance Standards.

HIV incidence is a primary metric for epidemic surveillance and prevention efficacy assessment. HIV incidence assay performance is evaluated via false recency rate (FRR) and mean duration of recent infection (MDRI). We conducted a meta-analysis of 438 incident and 305 chronic specimens' HIV envelope genes from a diverse global cohort. The genome similarity index (GSI) accurately characterized infection stage across diverse host and viral factors. All except one chronic specimen had GSIs below 0.67, yielding a FRR of 0.33 [0-0.98] %. We modeled the incidence assay biomarker dynamics with a logistic link function assuming individual variabilities in a Beta distribution. The GSI probability density function peaked close to 1 in early infection and 0 around two years post infection, yielding MDRI of 420 [361, 467] days. We tested the assay by newly sequencing 744 envelope genes from 59 specimens of 21 subjects who followed from HIV negative status. Both standardized residuals and Anderson-Darling tests showed that the test dataset was statistically consistent with the model biomarker dynamics. This is the first reported incidence assay meeting the optimal FRR and MDRI performance standards. Signatures of HIV gene diversification can allow precise cross-sectional surveillance with a desirable temporal range of incidence detection

Multi-Channel Stochastic Variational Inference for the Joint Analysis of Heterogeneous Biomedical Data in Alzheimer's Disease

The joint analysis of biomedical data in Alzheimer's Disease (AD) is important for better clinical diagnosis and to understand the relationship between biomarkers. However, jointly accounting for heterogeneous measures poses important challenges related to the modeling of the variability and the interpretability of the results. These issues are here addressed by proposing a novel multi-channel stochastic generative model. We assume that a latent variable generates the data observed through different channels (e.g., clinical scores, imaging, ...) and describe an efficient way to estimate jointly the distribution of both latent variable and data generative process. Experiments on synthetic data show that the multi-channel formulation allows superior data reconstruction as opposed to the single channel one. Moreover, the derived lower bound of the model evidence represents a promising model selection criterion. Experiments on AD data show that the model parameters can be used for unsupervised patient stratification and for the joint interpretation of the heterogeneous observations. Because of its general and flexible formulation, we believe that the proposed method can find important applications as a general data fusion technique.Comment: accepted for presentation at MLCN 2018 workshop, in Conjunction with MICCAI 2018, September 20, Granada, Spai

Post-fossilization processes and their implications for understanding Ediacaran macrofossil assemblages

Fossil assemblages from Newfoundland's Avalon Peninsula preserve diverse examples of the enigmatic Ediacaran macrobiota, offering some of the earliest evidence for large and complex multicellular life. These fossils are exposed on extensive coastal bedding planes in extraordinary abundances, permitting palaeoecological studies based on census data from spatially extensive palaeocommunities. Such studies have been used to constrain the reproductive strategy and phylogenetic placement of Ediacaran organisms. Geological mapping and stratigraphic correlation in the Mistaken Point Ecological Reserve reveal that some fossil-bearing surfaces can be tracked over distances of several kilometres. These laterally extensive surfaces reveal that the modern processes by which the sediment overlying a fossil surface is removed may impose important controls on the observed composition of fossil assemblages. Weathering and erosion – along with factors associated with tectonics, metamorphism and discovery – are here grouped as ‘post-fossilization processes’ and introduce biases that are often not explicitly accounted for in palaeoecological studies. Specifically, post-fossilization processes may differentially influence the preservational fidelity of individual specimens on a given surface and generate features that could be mistaken for original morphological characters. We therefore recommend that post-fossilization processes must be considered when undertaking palaeoecological studies in Ediacaran successions in Newfoundland and, potentially, elsewhere