Impact of Admission and Cache Replacement Policies on Response Times of Jobs on Data Grids

Caching techniques have been used widely to improve the performance gaps of storage hierarchies in computing systems. Little is known about the impact of policies on the response times of jobs that access and process very large files in data grids, particularly when data and computations on the data have to be co-located on the same host. In data intensive applications that access large data files over wide area network environment, such as data-grids, the combination of policies for job servicing (or scheduling), caching and cache replacement can significantly impact the performance of grid jobs. We present preliminary results of a simulation study that combines an admission policy with a cache replacement policy when servicing jobs submitted to a storage resource manager.The results show that, in comparison to a first come first serve policy, the response times of jobs are significantly improved, for practical limits of disk cache sizes, when the jobs that are back-logged to access the same files are taken into consideration in scheduling the next file to be retrieved into the disk cache. Not only are the response times of jobs improved, but also the metric measures for caching policies, such as the hit ratio and the average cost per retrieval, are improved irrespective of the cache replacement policy used. Ekow Otoo is research staff scientist with the scientific data management group at Lawrence Berkeley National Laboratory, University of California, Berkeley. He received his B.Sc. degree in Electrical Engineering from the University of Science and Technology, Kumasi, Ghana and a post graduate diploma in Computer Science from the University of Ghana, Legon. In 1977, he received his M.Sc. degree in Computer Science from the University of Newcastle Upon Tyne in Britain and his Ph.D. degree in Computer Science from McGill University, Montreal, Canada in 1983. He joined the faculty of the School of Computer Science, Carleton University, in 1983 and from 1987 to 1999, he was a tenured faculty member of the School of Computer Science, Carleton University, Ottawa, Canada. He has served as research consultant to Bell Northern Research, Ottawa, Canada, and as a research project consultant to the GIS Division, Geomatics Canada, Natural Resources Canada, from 1990 to 1998. Ekow Otoo is a member of the ACM and IEEE. His research interests include database management systems, data structures and algorithms, parallel I/O for high performance computing, parallel and distributed computing. Doron Rotem is currently a senior staff scientist and a member of the Data Management group at the Lawrence Berkeley National Lab. His research interests include Grid Computing, Workflow, Scientific Data Management and Paralled and Distributed Computing and Algorithms. He has published over 80 papers in international journals and conferences in these areas. Prior to that, Dr Rotem co-founded and served as a CTO of a startup company, called CommerceRoute, that made software products in the area of workflow and data integration and before that, he was an Associate Professor in the Department of Computer Science, University of Waterloo, Canada. Dr. Rotem holds a B.Sc degree in Mathematics and Statistics from the Hebrew University, Jerusalem, Israel and a Ph.D. in Computer Science from the University of the Witwatersrand, Johannesburg, South Africa. Arie Shoshani is a senior staff scientist at Lawrence Berkeley National Laboratory. He joined LBNL in 1976. He heads the Scientific Data Management Group. He received his Ph.D. from Princeton University in 1969. From 1969 to 1976, he was a researcher at System Development Corporation, where he worked on the Network Control Program for the ARPAnet, distributed databases, database conversion, and natural language interfaces to data management systems. His current areas of work include data models, query languages, temporal data, statistical and scientific database management, storage management on tertiary storage, and grid storage middleware. Arie is also the director of a Scientific Data Management (SDM) Integrated Software Infrastructure Center (ISIC), one of seven centers selected by the SciDAC program at DOE in 2001. In this capacity, he is coordinating the work of collaborators from 4 DOE laboratories and 4 universities (see: http://sdmcenter.lbl.gov). Dr. Shoshani has published over 65 technical papers in refereed journals and conferences, chaired several workshops, conferences, and panels in database management; and served on numerous program committees for various database conferences. He also served as an associate editor for the ACM Transactions on Database Systems. He was elected a member of the VLDB Endowment Board, served as the Publication Board Chairperson for the VLDB Journal, and as the Vice-President of the VLDB Endowment. His home page is http://www.lbl.gov/arie.     

Strong and ubiquitous expression of transgenes targeted into the beta-actin locus by Cre/lox cassette replacement

Conventional approaches to produce transgenic mice recurrently yield unpredictable patterns and levels of transgene expression, a situation calling for the development of new techniques to overcome these drawbacks in the context of overexpression studies. Here we present an efficient method for rapid and reproducible transgenesis using the recombinase mediated cassette exchange (RMCE) (Bouhassira et al.: Blood 90:3332-3344, 1997) procedure. A lox511-EGFP-TK/neo-loxP cassette was placed under the control of the endogenous mouse beta-actin promoter. Heterozygous mice revealed strong and ubiquitous EGFP expression throughout embryogenesis and adulthood. Reproducibly, the same expression pattern was obtained with RMCE when it was used to replace the EGFP-harboring cassette by ECFP or placental alkaline phosphatase (PLAP) reporter genes (DePrimo et al.: Transgenic Res 5:459-466, 1996). Furthermore, the RMCE procedure proved efficient as well in embryonic stem (ES) cells as directly in zygotes. Our results demonstrate ubiquitous expression of floxed transgenes in the endogenous beta-actin locus and they support the general use of the beta-actin locus for targeted transgenesis.     

Inhibition of HIV-1 envelope glycoprotein-mediated cell fusion by a DL-amino acid-containing fusion peptide: possible recognition of the fusion complex

The N-terminal fusion peptide (FP) of human immunodeficiency virus-1 (HIV-1) is a potent inhibitor of cell-cell fusion, possibly because of its ability to recognize the corresponding segments inside the fusion complex within the membrane. Here we show that a fusion peptide in which the highly conserved Ile(4), Phe(8), Phe(11), and Ala(14) were replaced by their d-enantiomers (IFFA) is a potent inhibitor of cell-cell fusion. Fourier transform infrared spectroscopy confirmed that despite these drastic modifications, the peptide preserved most of its structure within the membrane. Fluorescence energy transfer studies demonstrated that the diastereomeric peptide interacted with the wild type FP, suggesting this segment as the target site for inhibition of membrane fusion. This is further supported by the similar localization of the wild type and IFFA FPs to microdomains in T cells and the preferred partitioning into ordered regions within sphingomyelin/phosphatidyl-choline/cholesterol giant vesicles. These studies provide insight into the mechanism of molecular recognition within the membrane milieu and may serve in designing novel HIV entry inhibitors.     

Hyperphosphorylation and aggregation of tau in experimental autoimmune encephalomyelitis

Axonal damage is a major morphological correlate and cause of permanent neurological deficits in patients with multiple sclerosis (MS), a multifocal, inflammatory and demyelinating disease of the central nervous system. Hyperphosphorylation and pathological aggregation of microtubule-associated protein tau is a common feature of many neurodegenerative diseases with axonal degeneration including Alzheimer's disease. We have therefore analyzed tau phosphorylation, solubility and distribution in the brainstem of rats with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Tau was hyperphosphorylated at several sites also phosphorylated in Alzheimer's disease and became partially detergent-insoluble in EAE brains. Morphological examination demonstrated accumulation of amorphous deposits of abnormally phosphorylated tau in the cell body and axons of neurons within demyelinating plaques. Hyperphosphorylation of tau was accompanied by up-regulation of p25, an activator of cyclin-dependent kinase 5. Phosphorylation of tau, activation of cdk5, and axonal pathology were significantly reduced when diseased rats were treated with prednisolone, a standard therapy of acute relapses in MS. Hyperphosphorylation of tau was not observed in a genetic or nutritional model of axonal degeneration or demyelination, suggesting that inflammation as detected in the brains of rats with EAE is the specific trigger of tau pathology. In summary, our data provide evidence that axonal damage in EAE and possibly MS is linked to tau pathology.     

Hetero-assembly between all-L- and all-D-amino acid transmembrane domains: forces involved and implication for inactivation of membrane proteins

Protein-protein interactions within the membrane, partially or fully mediated by transmembrane (TM) domains, are involved in many vital cellular processes. Since the unique feature of the membrane environment enables protein-protein assembly that otherwise is not energetically favored in solution, the structural restrictions involved in the assembly of soluble proteins are not necessarily valid for the assembly of TM domains. Here we used the N-terminal TM domain (Tar-1) of the Escherichia coli aspartate receptor as a model system for examining the stereospecificity of TM-TM interactions in vitro and in vivo in isolated systems, and in the context of the full receptor. For this propose, we synthesized Tar-1 all-l and all-d amino acid TM peptides, a mutant TM peptide and an unrelated TM peptide. The data revealed: (i) Tar-1 all-d specifically associated with Tar-1 all-l within a model lipid membrane, as determined by using fluorescence energy transfer experiments; (ii) Tar-1 all-l and all-d, but not the control peptides, demonstrated a dose-dependant dominant negative effect on the Tar-1 TM homodimerization in the bacterial ToxR assembly system, suggesting a wild-type-like interaction; and most interestingly, (iii) both Tar-1 all-l and all-d showed a remarkable ability to inhibit the chemotaxis response of the full-length receptor, in vivo. Peptide binding to the bacteria was confirmed through confocal imaging, and Western blotting confirmed that ToxR Tar-1 chimera protein levels are not affected by the presence of the exogenous peptides. These findings present the first evidence that an all-d TM domain peptide acts in vivo similarly to its parental all-l peptide and suggest that the dimerization of the TM domains is mainly mediated by side-chain interactions, rather than geometrically fitted conformations. In addition, the study provides a new approach for modifying the function of membrane proteins by proteolysis-free peptides.     

The matrilineal ancestry of Ashkenazi Jewry: portrait of a recent founder event

Both the extent and location of the maternal ancestral deme from which the Ashkenazi Jewry arose remain obscure. Here, using complete sequences of the maternally inherited mitochondrial DNA (mtDNA), we show that close to one-half of Ashkenazi Jews, estimated at 8,000,000 people, can be traced back to only 4 women carrying distinct mtDNAs that are virtually absent in other populations, with the important exception of low frequencies among non-Ashkenazi Jews. We conclude that four founding mtDNAs, likely of Near Eastern ancestry, underwent major expansion(s) in Europe within the past millennium.     

Surface plasmon resonance for real-time evaluation of immobilized fructosyltransferase activity

The extracellular enzyme fructosyltransferase (FTF) is considered to be a significant virulence factor in the dental biofilm. We have developed a method using surface plasmon resonance to detect the activity of immobilized FTF in situ. This real time technique provides a sensitive direct assay for characterizing functional properties of immobilized enzymes such as FTF.