Deletion within the Src homology domain 3 of Bruton's tyrosine kinase resulting in X-linked agammaglobulinemia (XLA).

The gene responsible for X-linked agammaglobulinemia (XLA) has been recently identified to code for a cytoplasmic tyrosine kinase (Bruton's agammaglobulinemia tyrosine kinase, BTK), required for normal B cell development. BTK, like many other cytoplasmic tyrosine kinases, contains Src homology domains (SH2 and SH3), and catalytic kinase domain. SH3 domains are important for the targeting of signaling molecules to specific subcellular locations. We have identified a family with XLA whose affected members have a point mutation (g-->a) at the 5' splice site of intron 8, resulting in the skipping of coding exon 8 and loss of 21 amino acids forming the COOH-terminal portion of the BTK SH3 domain. The study of three generations within this kinship, using restriction fragment length polymorphism and DNA analysis, allowed identification of the mutant X chromosome responsible for XLA and the carrier status in this family. BTK mRNA was present in normal amounts in Epstein-Barr virus-induced B lymphoblastoid cell lines established from affected family members. Although the SH3 deletion did not alter BTK protein stability and kinase activity of the truncated BTK protein was normal, the affected patients nevertheless have a severe B cell defect characteristic for XLA. The mutant protein was modeled using the normal BTK SH3 domain. The deletion results in loss of two COOH-terminal beta strands containing several residues critical for the formation of the putative SH3 ligand-binding pocket. We predict that, as a result, one or more crucial SH3 binding proteins fail to interact with BTK, interrupting the cytoplasmic signal transduction process required for B cell differentiation

Fairness-Oriented User Scheduling for Bursty Downlink Transmission Using Multi-Agent Reinforcement Learning

In this work, we develop practical user scheduling algorithms for downlink bursty traffic with emphasis on user fairness. In contrast to the conventional scheduling algorithms that either equally divides the transmission time slots among users or maximizing some ratios without physcial meanings, we propose to use the 5%-tile user data rate (5TUDR) as the metric to evaluate user fairness. Since it is difficult to directly optimize 5TUDR, we first cast the problem into the stochastic game framework and subsequently propose a Multi-Agent Reinforcement Learning (MARL)-based algorithm to perform distributed optimization on the resource block group (RBG) allocation. Furthermore, each MARL agent is designed to take information measured by network counters from multiple network layers (e.g. Channel Quality Indicator, Buffer size) as the input states while the RBG allocation as action with a proposed reward function designed to maximize 5TUDR. Extensive simulation is performed to show that the proposed MARL-based scheduler can achieve fair scheduling while maintaining good average network throughput as compared to conventional schedulers.Comment: 30 pages, 13 figure

Rotational Reconstruction of Sapphire (0001)

The structure of the $(\sqrt{31}\times \sqrt{31})R\pm9^\circ$ reconstructed phase on sapphire (0001) surface is investigated by means of a simulation based on the energy minimization. The interaction between Al adatoms is described with the semi-empirical many-body Sutton-Chen potential, corrected for the charge transfer between the metallic overlayer and the substrate. The interactions between the Al adatoms and sapphire substrate are described with a simple three-dimensional potential field which has the hexagonal periodicity of sapphire surface. Our energy analysis gave evidence that the structure which is observed at room temperature is in fact a frozen high-temperature structure. In accordance with the X-ray scattering, a hexagonal domain pattern separated by domain walls has been found. The Al adatoms, distributed in two monolayers, are ordered and isomorphic to metallic Al(111) in the domains and disordered in the domain walls. The main reason for the rotational reconstruction is the lattice misfit between the metallic Al and sapphire.Comment: 15 pages with 4 eps figures in text. Uses psfig and elsart.cls (ELSEVIER Science). Submitted to Surf. Sc

Fuzzy logic damping controller for FACTS devices in interconnected power systems

Fuzzy controllers are designed for flexible AC transmission systems (FACTS) in interconnected power systems. Two typical FACTS devices, a static synchronous compensator (STATCOM) and a unified power flow controller (UPFC), are used as examples to show that FACTS devices with well-designed fuzzy controllers can significantly improve the dynamic behavior of interconnected power systems.published_or_final_versio

Sparse Optical Arbitrary Waveform Measurement by Compressive Sensing

We propose and experimentally demonstrate a compressive sensing scheme based on optical coherent receiver that recovers sparse optical arbitrary signals with an analog bandwidth up to 25GHz. The proposed scheme uses 16x lower sampling rate than the Nyquist theorem and spectral resolution of 24.4MHz

Gene Structure Evolution of the Na+-Ca2+ Exchanger (NCX) Family

<p>Abstract</p> <p>Background</p> <p>The Na⁺-Ca²⁺exchanger (NCX) is an important regulator of cytosolic Ca²⁺levels. Many of its structural features are highly conserved across a wide range of species. Invertebrates have a single <it>NCX </it>gene, whereas vertebrate species have multiple <it>NCX </it>genes as a result of at least two duplication events. To examine the molecular evolution of <it>NCX </it>genes and understand the role of duplicated genes in the evolution of the vertebrate <it>NCX </it>gene family, we carried out phylogenetic analyses of <it>NCX </it>genes and compared <it>NCX </it>gene structures from sequenced genomes and individual clones.</p> <p>Results</p> <p>A single <it>NCX </it>in invertebrates and the protochordate <it>Ciona</it>, and the presence of at least four <it>NCX </it>genes in the genomes of teleosts, an amphibian, and a reptile suggest that a four member gene family arose in a basal vertebrate. Extensive examination of mammalian and avian genomes and synteny analysis argue that <it>NCX4 </it>may be lost in these lineages. Duplicates for <it>NCX1</it>, <it>NCX2</it>, and <it>NCX4 </it>were found in all sequenced teleost genomes. The presence of seven genes encoding <it>NCX </it>homologs may provide teleosts with the functional specialization analogous to the alternate splicing strategy seen with the three <it>NCX </it>mammalian homologs.</p> <p>Conclusion</p> <p>We have demonstrated that <it>NCX4 </it>is present in teleost, amphibian and reptilian species but has been secondarily and independently lost in mammals and birds. Comparative studies on conserved vertebrate homologs have provided a possible evolutionary route taken by gene duplicates subfunctionalization by minimizing homolog number.</p

Overcoming gaps to advance global health equity: a symposium on new directions for research

<p>Abstract</p> <p>The 20^thanniversary of the groundbreaking report of the Commission on Health Research for Development inspired a Symposium to assess progress made in strengthening essential national health research capacity in developing countries and in global research partnerships. Significant aspects of the health gains achieved in the 20^thcentury can be attributed to the advancement and translation of knowledge, and knowledge continues to occupy center stage amidst growing complexity that characterizes the global health field. The way forward will entail a reinvigoration of research-generated knowledge as a crucial ingredient for global cooperation and global health advances. To do this we will need to overcome daunting gaps, including the divides between domestic and global health, among the disciplines of research (biomedical, clinical, epidemiological, health systems), between clinical and public health approaches, public and private investments, and between knowledge gained and action implemented. Overcoming systematically these obstacles can accelerate progress towards research for equity in health and development.</p