Profound Depletion of HIV-1 Transcription in Patients Initiating Antiretroviral Therapy during Acute Infection

Early intervention resulted in profound depletion of PBMC expressing HIV-1 RNA. This is contrary to chronically infected patients who predominantly showed continuous UsRNA expression on cART. Thus, antiretroviral treatment initiated during the acute phase of infection prevented establishment or expansion of long-lived transcriptionally active viral cellular reservoirs in peripheral blood

Rational design of HIV-1 fluorescent hydrolysis probes considering phylogenetic variation and probe performance

Quantitative PCR (qPCR) using fluorescent hydrolysis probes (FH-probes; TaqMan®-probes) of variable genomes, such as HIV-1, can result in underestimation of viral copy numbers due to mismatches in the FH-probe's target sequences. Therefore both target conservation and physical properties of FH-probes, such as melting temperature, baseline fluorescence and secondary structure, should be considered in design of FH-probes. Analysis of a database of 1242 near full-length HIV-1 sequences with a novel computational tool revealed that the probability of target and FH-probe identity decreases exponentially with FH-probe length. In addition, this algorithm allowed for identification of continuous sequence stretches of high conservation, from which FH-probes with global HIV-1 clade coverage could be chosen. To revise the prerequisites of physical FH-probe function, properties of 30 DNA and 21 chimeric DNA locked nucleic acid (DLNA) HIV-1 FH-probes were correlated with their performance in qPCR. This identified the presence of stable secondary structures within FH-probes and the base composition and thermal stability of the 5′ proximal end as novel predictors of FH-probe performance. Thus, empirically validated novel principles of FH-probe design regarding conservation and qPCR-performance were identified, which complement and extend current rules for FH-probe design

Objectivity/CORBA distributed database performance on a Gigabit SUN-Ultra-10 cluster

Dynacore's project objective is to provide tools for the remote operation of large physics experiments [1], [2], [3]. Our group concentrates on the design of a remote control room for the Textor-94 plasma-physics experiment [4], which will incorporate a distributed database, accessible with Corba over Internet [5]. During normal operation, Textor-94 generates hundreds of megabytes of measurement data within the few seconds of a plasma shot. These shots are generated approximately every ten minutes, in total around 30 shots per day. A database will make the measurement data available to scientists, both at the experiment and in remote control rooms, which can be located in different countries, within minutes after the acquisition. Fast access to the database and a high data-storage speed are, therefore, of utmost importance.We have defined a set of data objects, which allow storage of virtually any kind of Terror measurement data. An Objectivity [6] object-oriented database is used to store these objects. We have also designed an architecture in which database clients access the measurement database solely via data managers with Corba-interfaces. The data managers introduce security into the database, and also hide details of the database implementation for the users. An object manager provides clients with a central starting point, and distributes the total database load in an intelligent way over all available data-managers.We have tested the performance of our architecture on a computer cluster consisting of eight Sun-Ultra-10 workstations [7]. These computers are interconnected with 1-gigabit/s Ethernet fiber-optic links over two Cabletron SSR-8000 IP routers, and also via 100 Mbit/s Ethernet UTP cables over one Cabletron SS-6000 [8]. This article will discuss the database model, the distributed architecture and the performance measurements results. The measurements showed that our high performance goals can be achieved with the presented architecture