Coupling Between B Cell Receptor and Phospholipase C-γ2 Is Essential for Mature B Cell Development

Two signaling pathways known to be essential for progression from immature to mature B cells are BAFF receptor (BAFF-R) and the B cell receptor (BCR). Here, we first show that phospholipase C (PLC)-γ2 is required for a BAFF-R–mediated survival signal. Then, we have examined the question of whether the reduced number of mature B cells in PLC-γ2−/− mice is caused by a defect in either BCR or BAFF-R signaling. We find that a PLC-γ2 SH2 mutant, which inhibits coupling between BCR and PLC-γ2, fails to restore B cell maturation, despite supporting BAFF-dependent survival. Therefore, our data suggest that the BAFF-R–mediated survival signal, provided by PLC-γ2, is not sufficient to promote B cell maturation, and that, in addition, activation of PLC-γ2 by BCR is required for B cell development

Spatial profiles of collimated laser Compton-scattering γ\gamma-ray beams

The intensity and energy spatial distributions of collimated laser Compton scattering (LCS) $\gamma$-ray beams and of the associated bremsstrahlung beams have been investigated as functions of the electron beam energy, electron beam phase space distribution, laser optics conditions and laser polarization. We show that the beam halo is affected to different extents by variations in the above listed parameters. In the present work, we have used laser Compton scattering simulations performed with the \texttt{eliLaBr} code (https://github.com/dan-mihai-filipescu/eliLaBr) and real LCS and bremsstrahlung $\gamma$-ray beams produced at the NewSUBARU synchrotron radiation facility. A 500~$\mu$m MiniPIX X-ray camera was used as beamspot monitor in a wide $\gamma$-ray beam energy range between 1.73~MeV and 38.1~MeV

Requirement for Ras Guanine Nucleotide Releasing Protein 3 in Coupling Phospholipase C-γ2 to Ras in B Cell Receptor Signaling

Two important Ras guanine nucleotide exchange factors, Son of sevenless (Sos) and Ras guanine nucleotide releasing protein (RasGRP), have been implicated in controlling Ras activation when cell surface receptors are stimulated. To address the specificity or redundancy of these exchange factors, we have generated Sos1/Sos2 double- or RasGRP3-deficient B cell lines and determined their ability to mediate Ras activation upon B cell receptor (BCR) stimulation. The BCR requires RasGRP3; in contrast, epidermal growth factor receptor is dependent on Sos1 and Sos2. Furthermore, we show that BCR-induced recruitment of RasGRP3 to the membrane and the subsequent Ras activation are significantly attenuated in phospholipase C-γ2–deficient B cells. This defective Ras activation is suppressed by the expression of RasGRP3 as a membrane-attached form, suggesting that phospholipase C-γ2 regulates RasGRP3 localization and thereby Ras activation

Contrastive Decoding: Open-ended Text Generation as Optimization

Likelihood, although useful as a training loss, is a poor search objective for guiding open-ended generation from language models (LMs). Existing generation algorithms must avoid both unlikely strings, which are incoherent, and highly likely ones, which are short and repetitive. We propose contrastive decoding (CD), a more reliable search objective that returns the difference between likelihood under a large LM (called the expert, e.g. OPT-13b) and a small LM (called the amateur, e.g. OPT-125m). CD is inspired by the fact that the failures of larger LMs are even more prevalent in smaller LMs, and that this difference signals exactly which texts should be preferred. CD requires zero training, and produces higher quality text than decoding from the larger LM alone. It also generalizes across model types (OPT and GPT2) and significantly outperforms four strong decoding algorithms in automatic and human evaluations

Neutrino Masses and a Fourth Generation of Fermions

We study neutrino mass generation in models with four chiral families of leptons and quarks and four right handed neutrinos. Generically, in these models there are three different contributions to the light neutrino masses: the usual see-saw contribution, the tree-level contribution due to mixing of light neutrinos with neutrino of the fourth generation, and the two loop contribution due to the Majorana mass term of the fourth neutrino. We study properties of these contributions and their experimental bounds. The regions of the parameters (mixings of the fourth neutrino, masses of RH neutrino components, etc.) have been identified where various contributions dominate. New possibilities of a realization of the flavour symmetries in the four family context are explored. In particular, we consider applications of the smallest groups, e.g. SG(20,3), with irreducible representation 4.Comment: 33 pages, 4 figures; Eq. (18) corrected and thus corrections to Eqs. (21,26-28,41,42,44-46) and figures, the loop contribution reduced by 2 orders of magnitude; general conclusions unchanged; accepted by Nucl. Phys.

A Spin Chain for the Symmetric Product CFT_2

We consider "gauge invariant" operators in Sym^N T^4, the symmetric product orbifold of N copies of the 2d supersymmetric sigma model with T^4 target. We discuss a spin chain representation for single-cycle operators and study their two point functions at large N. We perform systematic calculations at the orbifold point ("tree level"), where non-trivial mixing is already present, and some sample calculations to first order in the blow-up mode of the orbifold ("one loop").Comment: 52 pages, 10 figure

Gene Organization in Rice Revealed by Full-Length cDNA Mapping and Gene Expression Analysis through Microarray

Rice (Oryza sativa L.) is a model organism for the functional genomics of monocotyledonous plants since the genome size is considerably smaller than those of other monocotyledonous plants. Although highly accurate genome sequences of indica and japonica rice are available, additional resources such as full-length complementary DNA (FL-cDNA) sequences are also indispensable for comprehensive analyses of gene structure and function. We cross-referenced 28.5K individual loci in the rice genome defined by mapping of 578K FL-cDNA clones with the 56K loci predicted in the TIGR genome assembly. Based on the annotation status and the presence of corresponding cDNA clones, genes were classified into 23K annotated expressed (AE) genes, 33K annotated non-expressed (ANE) genes, and 5.5K non-annotated expressed (NAE) genes. We developed a 60mer oligo-array for analysis of gene expression from each locus. Analysis of gene structures and expression levels revealed that the general features of gene structure and expression of NAE and ANE genes were considerably different from those of AE genes. The results also suggested that the cloning efficiency of rice FL-cDNA is associated with the transcription activity of the corresponding genetic locus, although other factors may also have an effect. Comparison of the coverage of FL-cDNA among gene families suggested that FL-cDNA from genes encoding rice- or eukaryote-specific domains, and those involved in regulatory functions were difficult to produce in bacterial cells. Collectively, these results indicate that rice genes can be divided into distinct groups based on transcription activity and gene structure, and that the coverage bias of FL-cDNA clones exists due to the incompatibility of certain eukaryotic genes in bacteria