Identification of a CD4+ T cell-stimulating antigen of pathogenic bacteria by expression cloning.

Identifying the immunogenic proteins that elicit pathogen-specific T cell responses is key to rational vaccine design. While several approaches have succeeded in identifying major histocompatibility complex (MHC) class I bound peptides that stimulate CD8+ T cells, these approaches have been difficult to extend to peptides presented by MHC class II molecules that stimulate CD4+ T cells. We describe here a novel strategy for identifying CD4+ T cell-stimulating antigen genes. Using Listeria monocytogenes-specific, lacZ-inducible T cells as single-cell probes, we screened a Listeria monocytogenes genomic library as recombinant Escherichia coli that were fed to macrophages. The antigen gene was isolated from the E. coli clone that, when ingested by the macrophages, allowed generation of the appropriate peptide/MHC class II complex and T cell activation. We show that the antigenic peptide is derived from a previously unknown listeria gene product with characteristics of a membrane-bound protein

Magnetic Field Geometry in "Red" and "Blue" BL Lacs

We compare the systematics of the magnetic field geometry in the "red" low-energy peaked BL Lacs (LBLs) and "blue" high-energy peaked BL Lacs (HBLs) using VLBI polarimetric images. The LBLs are primarily "radio--selected" BL Lacs and the HBLs are primarily "X-ray selected". In contrast to the LBLs, which show predominantly transverse jet magnetic fields, the HBLs show predominantly longitudinal fields. Thus, while the SED peaks of core-dominated quasars, LBLs and HBLs form a sequence of increasing frequency, the magnetic field geometry does not follow an analogous sequence. We briefly investigate possible connections between the observed parsec-scale magnetic field structures and circular polarization measurements in the literature on various spatial scales.Comment: 12 pages, 5 figures, Proceedings of the Amsterdam workshop on "Circular polarisation from relativistic jet sources", to be published in Astrophysics and Space Science, eds. Rob Fender & J-P Macquar

Characterization of the Blackpatch mutation in Drosophila melanogaster

Mutations at the Blackpatch locus cause death and degeneration in the developing visual system of Drosophila melanogaster. Some Bpt alleles cause recessive lethality in the larval stage during development. To understand the role of Bpt in visual system development, the mutant phenotype was characterized for its effects on structure of the developing eye and the electrical activity of adult mutant eyes. The first hypothesis was that Bpt gene function may be required for the visual transduction pathway to receive and process light signals correctly. This is an electrical/biochemical process that can be visualised as an electroretinogram (ERG) and mutations in the pathway lead to abnormal ERGs. Bpt mutations may affect this pathway causing abnormal electroretinograms (ERGs). Analyses of the electroretinograms of mutant flies showed that mutant flies receive and process light correctly. Bpt does not function in the visual transduction pathway. The second hypothesis was that Bpt functions in a neurotrophic pathway. Genes in this pathway interact with signal transduction pathways necessary for cell-cell signaling and exhibit temporal and spatial specificity. Mutations in this pathway characteristically cause cell death in an apoptotic manner. In Bpt mutants, cell death in the developing eye occurs in a spatial and temporally specific manner suggesting a similar specificity for the action of the Bpt gene. The genetic focus of the mutation is in the lamina which is seen first around 42 hours post pupariation (pp) followed by death in the retina around 58 hours pp. Previous analyses has shown that Bpt interacts with Notch , an important cell signaling molecule that communicates by sending lateral inhibitory signals to its neighbors. The Bpt mutation affects the eye at a time of axonal innervation of the lamina. In mammalian systems, this phase involves the action of neurotrophic genes. Several lines of evidence suggest that Bpt may indeed be working in a neurotrophic pathway to maintain the laminar cells as they complete development;In the developing fly, Bpt mutations cause lethality in the homozygous condition. The lethal phase for Bpt is between 36 to 48 hours during the larval II instar phase of development. This suggests a time when the Bpt gene product is needed. The lethal phase is at a time of proliferation and development in the nervous system. Our results show that the morphology of the nervous system is normal at the end of embryogenesis. Bpt is necessary at a very specific time in development and any abnormalities due to Bpt take place during this time window. It is possible that the systemic death of the larva is due to multiple primary and secondary effects of the Bpt mutation. We suggest that Bpt has a vital function and this may be involved in the proliferation of the central brain neuroblasts during development;Blackpatch plays an important role in the development of Drosophila. In the adult visual system development it may be acting within a neurotrophic pathway that is necessary for maturation and maintenance when the retinal axons are innervating the lamina. In the larva, Bpt may again be functioning as part of a neurotrophic pathway in central nervous system development

Imatinib Resistance and Relapse in CML Patients with Complex Chromosomal Variants

The BCR-ABL tyrosine kinase inhibitor Imatinib is highly effective for chronic myeloid leukemia (CML). However, some patients gradually develop resistance to Imatinib, resulting in therapeutic failure. In the present study, we analyzed 192 CML patients, from which CML relapse was observed in 17 individuals with involvement of other chromosomes in addition to Philadelphia translocation and who were on treatment of Imatinib (400mg per day since last 3-4 years). Interestingly, all 17 individuals had only BCR/ABL fusion at the time of diagnosis and attained complete Cytogenetic and hematological remission (CHR) within 18 weeks of the therapy. Three individuals among these 17 were not regular in the uptake of Imatinib after attaining CHR and CCyR and could be probable reason for relapse. In addition, we have also recorded primary resistance to Imatinib in 4 individuals who were diagnosed with some complex chromosomal variants. Therefore, either involvement of other genes along with BCR/ABL fusion, or additional chromosomes and point mutation in the fusion BCR/ABL gene itself could be a reason for primary resistance and relapse to Imatinib

Massively Parallel Simulation of Structured Connectionist Networks: An Interim Report

We map structured connectionist models of knowledge representation and reasoning onto existing general purpose massively parallel architectures with the objective of developing and implementing practical, real-time knowledge base systems. Shruti, a connectionist knowledge representation and reasoning system which attempts to model reflexive reasoning, will serve as our representative connectionist model. Efficient simulation systems for shruti are developed on the Connection Machine CM-2 - an SIMD architecture - and on the Connection Machine CM-5 - an MIMD architecture. The resulting simulators are evaluated and tested using large, random knowledge bases with up to half a million rules and facts. Though SIMD simulations on the CM-2 are reasonably fast - requiring a few seconds to tens of seconds for answering simple queries - experiments indicate that MIMD simulations are vastly superior to SIMD simulations and offer hundred- to thousand-fold speedups. This work provides new insights into the simulation of structured connectionist networks on massively parallel machines and is a step toward developing large yet efficient knowledge representation and reasoning systems

Silicon saw-tooth refractive lens for high-energy X-rays made using a diamond saw

A Si saw-tooth refractive lens, fabricated by a dicing process, is demonstrated to focus a 115 keV X-ray beam

Virtual DBA for SQL Thin Client

The users has to connect the company database remotely and make requested changes. This project allows the users to connect with the database without having any client software�s to be installed. The DBA and the other employees working on MS SQL Server can access it if and if it is installed in the machine, if the MS SQL server is not installed it is impossible to get connected and work with the server. If the DBA is not in the organization and it is very immediately require restoring or taking the back-up of the database or any other tsk like that, the DBA can get connected to the server only through a machine in which MS SQL server is installed. The only requirement is web browser. The current study presents a tool for remote database administration that is executed through web application. The web application provides database administrators (DBAs) to perform their task by automatically identifying databases. The proposed tool provides database administrationservices anywhere and anytime. Furthermore, the proposed tool enables DBAs to Manage databaseresiding in mobile hosts or famed hosts. The MS SQL Server has to be installed in the server machines, through which the workers will access the respective databases to write there codes. The DBA too can access the MS SQL Server only if it installed in the machine. If MS SQL Server is not installed in the machine neither the DBA can access the server nor can the workers access it. Therefore in the present study we are developing a web application which helps us to perform the entire DBA tasks can creating user, setting the access permissions, creating databases, taking back-up of the database, restoring the database etc

External auditor\u27s ethical dilemma: Perceived threat to auditor\u27s responsibility posed by the auditor\u27s allegiance to corporate management

Major accounting scandals and audit failures (such as Enron and WorldCom) during the turn of the century seriously impaired the public\u27s confidence and trust in audited financial statements. This had cast a shadow on auditor independence, integrity and professional conduct, and led to the collapse of Arthur Andersen (AA), one of the then Big-5 public accounting firms. Some have argued that auditors align their interest with that of corporate management instead of investors and the general public because audit fees are paid by management. This leads to the following question: do auditors appear to compromise their independence and align with their clients\u27 interest rather than shareholders\u27 interest? Our examination of audit fees charged by the Big-5 to a sample of companies investigated by the Securities and Exchange Commission (SEC) reveals that auditors (except for AA) appear to recognize engagement risk at an increased level for SEC investigated audit clients. Accordingly, SEC investigated clients are charged higher audit fees than non-SEC investigated clients. However, AA appeared not to distinguish the engagement risk differences between its SEC investigated and non-SEC investigated clients. Results overall suggest that auditors fulfill their professional responsibility of serving the public interest by maintaining client-auditor independence and objectivity. Although the Sarbanes-Oxley Act of 2002 has been implemented, misleading and fraudulent financial reporting persist, which suggests that there is room for improving audit quality. Accordingly, we provide suggestions to strengthen both audit quality and professional conduct (particularly regarding auditor independence) to enhance the public\u27s confidence in audited financial statements