Delayed Cellular Maturation and Decreased Immunoglobulin κ Light Chain Production In Immature B Lymphocytes Lacking B Cell Linker Protein

B cell linker (BLNK) protein is a component of the B cell receptor (BCR) signaling pathway and BLNK−/− mice have a block in B lymphopoiesis at the pro-B/pre-B cell stage. To study the effect of BLNK mutation at later stages of B cell development, we introduce an innocuous transgenic BCR into BLNK−/− mice and show that two populations of immature B cells distinguishable by their IgMlow (lo) and IgMhigh (hi) phenotypes are found in the bone marrow of these mice in contrast to a single population of IgMhi cells found in control BCR-transgenic BLNK+/+ mice. The mutant IgMlo and IgMhi cells are at an earlier developmental stage compared with the control IgMhi cells as indicated by their differential expression of CD43, B220, and major histocompatibility complex class II antigens and their timing of generation in culture. Thus, in the absence of BLNK the differentiation of immature B cells is delayed. Furthermore, mutant IgMlo cells produce equivalent level of immunoglobulin (Ig) μ but less Ig κ proteins than control and mutant IgMhi cells and this defect is attributed to a decrease in the amount of κ transcripts being generated. Finally, splenic B cells in BCR-transgenic BLNK−/− mice are predominantly of the transitional B cell phenotype and are rapidly lost from the peripheral B cell pool. Taken together, the data suggest a role for BLNK and perhaps BCR signaling, in the regulation of κ light chain expression and continued immature B cell differentiation

Streamlined Data Fusion: Unleashing the Power of Linear Combination with Minimal Relevance Judgments

Linear combination is a potent data fusion method in information retrieval tasks, thanks to its ability to adjust weights for diverse scenarios. However, achieving optimal weight training has traditionally required manual relevance judgments on a large percentage of documents, a labor-intensive and expensive process. In this study, we investigate the feasibility of obtaining near-optimal weights using a mere 20\%-50\% of relevant documents. Through experiments on four TREC datasets, we find that weights trained with multiple linear regression using this reduced set closely rival those obtained with TREC's official "qrels." Our findings unlock the potential for more efficient and affordable data fusion, empowering researchers and practitioners to reap its full benefits with significantly less effort.Comment: 12 pages, 8 figure

Advanced Modeling and Design Methodology for Pavements using Plasticity-Based Shakedown Theory

Pavement design is a process intended to find the most economical combination of layer thickness and material type for the pavement, taking into account the properties of the subgrade soil and the traffic to be carried during the service life of the road. The currently prevalent methods of pavement analysis and design, however, are more or less empirical in U.S., which possess the shortcoming that the important type of pavement distress of rutting related to the accumulation of plastic or permanent deformations cannot be effectively considered. This project proposes an exploratory study on the application of the plasticity theory-based shakedown concept to the analysis and design of pavements under repeated loading, with a more realistic incorporation of the roughness impact of the top pavement layer on the dynamic amplification of vehicle loading as well as on the elastic stress responses in the underlying subsoils. Numerical results from the newly developed vehicle-road coupling model show that the total vehicle load amplification factor ranges from 0.88 to 1.16 under different roughness levels and traveling speeds. This indicates the necessity and importance of incorporating the factors of roughness/vehicle speed in the pavement response analysis. Extensive parametric analyses for the shakedown limit show that increases in the pavement cohesion strength and internal friction angle and in the pavement thickness have a positive influence on the calculated shakedown limit value. The analysis results also indicate that there generally exists an optimal Young’s modulus ratio between the pavement and subsoil, for which a maximum shakedown load of the pavement system will be reached. The outcomes of this project on one hand add contributions to the development of a more rational theoretical framework for the pavement design/analysis. On the other hand, the shakedown design approach can prevent the flexible pavement from excessive rutting failure, and hence is of great practical value for prediction/design of the vehicle load, traveling speed, and layer thickness that is required to warrant shakedown state of the pavements (i.e., no excessive rutting) in the long run

DD correlations as a sensitive probe for thermalization in high-energy nuclear collisions

We propose to measure azimuthal correlations of heavy-flavor hadrons to address the status of thermalization at the partonic stage of light quarks and gluons in high-energy nuclear collisions. In particular, we show that hadronic interactions at the late stage cannot significantly disturb the initial back-to-back azimuthal correlations of DDbar pairs. Thus, a decrease or the complete absence of these initial correlations does indicate frequent interactions of heavy-flavor quarks and also light partons in the partonic stage, which are essential for the early thermalization of light partons

China’s Scientific Journals in a Transforming Period: Present Situation and Developing Strategies

Based on a detailed analysis of the global academic impact of China’s scientific journals, as well as of the publishing strategies and communication media used by their publishers, we conclude that the Science, Technology, and Medicine (STM) journal publishing industry in China is going through very rapid transformation. Journals are attempting to become more broadly international, and doing so by adopting new digital production methods and commercial models. In light of these efforts, we discuss the current challenges to the development of China’s scientific journal industry and suggest strategies that may be useful for reaching key goals

Ganoderma lucidum Protects Dopaminergic Neuron Degeneration through Inhibition of Microglial Activation

Abundant evidence has suggested that neuroinflammation participates in the pathogenesis of Parkinson's disease (PD). The emerging evidence has supported that microglia may play key roles in the progressive neurodegeneration in PD and might be a promising therapeutic target. Ganoderma lucidum (GL), a traditional Chinese medicinal herb, has been shown potential neuroprotective effects in our clinical trials that make us to speculate that it might possess potent anti-inflammatory and immunomodulating properties. To test this hypothesis, we investigated the potential neuroprotective effect of GL and possible underlying mechanism of action through protecting microglial activation using co-cultures of dopaminergic neurons and microglia. The microglia is activated by LPS and MPP+-treated MES 23.5 cell membranes. Meanwhile, GL extracts significantly prevent the production of microglia-derived proinflammatory and cytotoxic factors [nitric oxide, tumor necrosis factor-α (TNF-α), interlukin 1β (IL-1β)] in a dose-dependent manner and down-regulate the TNF-α and IL-1β expressions on mRNA level as well. In conclusion, our results support that GL may be a promising agent for the treatment of PD through anti-inflammation