3'-UTR SIRF: A database for identifying clusters of short interspersed repeats in 3' untranslated regions

BACKGROUND:Short (~5 nucleotides) interspersed repeats regulate several aspects of post-transcriptional gene expression. Previously we developed an algorithm (REPFIND) that assigns P-values to all repeated motifs in a given nucleic acid sequence and reliably identifies clusters of short CAC-containing motifs required for mRNA localization in Xenopus oocytes.DESCRIPTION:In order to facilitate the identification of genes possessing clusters of repeats that regulate post-transcriptional aspects of gene expression in mammalian genes, we used REPFIND to create a database of all repeated motifs in the 3' untranslated regions (UTR) of genes from the Mammalian Gene Collection (MGC). The MGC database includes seven vertebrate species: human, cow, rat, mouse and three non-mammalian vertebrate species. A web-based application was developed to search this database of repeated motifs to generate species-specific lists of genes containing specific classes of repeats in their 3'-UTRs. This computational tool is called 3'-UTR SIRF (Short Interspersed Repeat Finder), and it reveals that hundreds of human genes contain an abundance of short CAC-rich and CAG-rich repeats in their 3'-UTRs that are similar to those found in mRNAs localized to the neurites of neurons. We tested four candidate mRNAs for localization in rat hippocampal neurons by in situ hybridization. Our results show that two candidate CAC-rich (Syntaxin 1B and Tubulin beta4) and two candidate CAG-rich (Sec61alpha and Syntaxin 1A) mRNAs are localized to distal neurites, whereas two control mRNAs lacking repeated motifs in their 3'-UTR remain primarily in the cell body.CONCLUSION:Computational data generated with 3'-UTR SIRF indicate that hundreds of mammalian genes have an abundance of short CA-containing motifs that may direct mRNA localization in neurons. In situ hybridization shows that four candidate mRNAs are localized to distal neurites of cultured hippocampal neurons. These data suggest that short CA-containing motifs may be part of a widely utilized genetic code that regulates mRNA localization in vertebrate cells. The use of 3'-UTR SIRF to search for new classes of motifs that regulate other aspects of gene expression should yield important information in future studies addressing cis-regulatory information located in 3'-UTRs.

A Performance Evaluation of Hyper Text Transfer Protocols

Version 1.1 of the Hyper Text Transfer Protocol (HTTP) was principally developed as a means for reducing both document transfer latency and network traffic. The rationale for the performance enhancements in HTTP/1.1 is based on the assumption that the network is the bottleneck in Web transactions. In practice, however, the Web server can be the primary source of document transfer latency. In this paper, we characterize and compare the performance of HTTP/1.0 and HTTP/1.1 in terms of throughput at the server and transfer latency at the client. Our approach is based on considering a broader set of bottlenecks in an HTTP transfer; we examine how bottlenecks in the network, CPU, and in the disk system affect the relative performance of HTTP/1.0 versus HTTP/1.1. We show that the network demands under HTTP/1.1 are somewhat lower than HTTP/1.0, and we quantify those differences in terms of packets transferred, server congestion window size and data bytes per packet. We show that when the CPU is the bottleneck, there is relatively little difference in performance between HTTP/1.0 and HTTP/1.1. Surprisingly, we show that when the disk system is the bottleneck, performance using HTTP/1.1 can be much worse than with HTTP/1.0. Based on these observations, we suggest a connection management policy for HTTP/1.1 that can improve throughput, decrease latency, and keep network traffic low when the disk system is the bottleneck.

On Class-based Isolation of UDP, Short-lived and Long-lived TCP Flows

The congestion control mechanisms of TCP make it vulnerable in an environment where flows with different congestion-sensitivity compete for scarce resources. With the increasing amount of unresponsive UDP traffic in today's Internet, new mechanisms are needed to enforce fairness in the core of the network. We propose a scalable Diffserv-like architecture, where flows with different characteristics are classified into separate service queues at the routers. Such class-based isolation provides protection so that flows with different characteristics do not negatively impact one another. In this study, we examine different aspects of UDP and TCP interaction and possible gains from segregating UDP and TCP into different classes. We also investigate the utility of further segregating TCP flows into two classes, which are class of short and class of long flows. Results are obtained analytically for both Tail-drop and Random Early Drop (RED) routers. Class-based isolation have the following salient features: (1) better fairness, (2) improved predictability for all kinds of flows, (3) lower transmission delay for delay-sensitive flows, and (4) better control over Quality of Service (QoS) of a particular traffic type.