49 research outputs found

    Web 2.0 Tools Ease Renovation Service Disruptions at The Ohio State University Libraries

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    The Thompson Library, the main library of The Ohio State University (OSU), began a major renovation in fall 2006 that required the library to close for three years. During this time, the bulk of the circulating collection and many of the personnel relocated to an interim facility. The distance imposed by the renovation created special challenges for service to patrons and communication among library faculty and staff. The OSU Libraries used blogs, podcasts, a wiki, instant messaging, and the campus course management system to reach as many of the constituents of the campus community as possible

    Alternative Solutions for Off-Campus Authentication

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    The Ohio State University Libraries created scripts to overcome the local limitations of the proxy server and to offer resource connections at the point of need. All libraries struggle to provide seamless authentication for access to paid resources, such as research databases and electronic journals. In order to obtain access to this content, the libraries must sign contracts promising to limit access to these resources to their user community. The challenge then comes in balancing the patron’s need for easy access to these rich data sources from any computer and the vendors’ desire to protect their assets

    971-54 A Non-invasive Method of Visually Assessing Renal Perfusion Using a Newly Developed Intravenous Ultrasound Contrast

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    Present methods of quantifying renal artery blood flow (RABF) in renovascular disease require either radionuclide techniques or invasive delivery of radiographic or ultrasound contrast. Perfluoropropane is a gas routinely used for intraocular injections which, when sonicated with dextrose albumin (PESDA). produces microbubbles with prolonged survival in blood. We hypothesized, therefore, that this prolonged ultrasound contrast effect could be utilized to non-invasively evaluate RABF and perfusion, Accordingly, we gave intravenous injections (IVI) of PESDA (0.06 cc/kg) to seven dogs while imaging with an external 4.5 MHz linear array transducer RABF was monitored using a Transonic Doppler probe placed around the renal artery. Contrast two-dimensional enhancement was quantified off-line. Both echo and color Doppler enhancement were also qualitatively graded as 0=no enhancement, 1+=mild, 2+=marked enhancement.Following all 36 (100%) IVI of PESDA, there was 2+ contrast ultrasound enhancement of the renal cortex. A linear correlation existed between Doppler renal artery flow and peak renal cortex videointensity follOWing IV PESDA (r=0.65, P<0.001), Color Doppler signals were also enhanced following IV PESDA, and resulted in excellent visualization of the main renal artery as well as segmental and lobar arteries. When renal artery stenosis was induced to decrease RABF to less than 10% of baseline, the segmental and lobar arteries were not visualized with color Doppler following IV PESDA, and peak renal cortex videointensity was reduced from 26 ± 10 to 15 ± 8 units (p<0.05). These data demonstrate that renal artery and cortical blood flow abnormalities can be detected using intravenous PESDA. This ultrasound contrast agent could be a new non-invasive method to detect renal artery stenosis or abnormal renal perfusion

    Active impedance matching of a cryogenic radio frequency resonator for ion traps

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    A combination of direct current (DC) fields and high amplitude radio frequency (RF) fields is necessary to trap ions in a Paul trap. Such high electric RF fields are usually reached with the help of a resonator in close proximity to the ion trap. Ion trap based quantum computers profit from good vacuum conditions and low heating rates that cryogenic environments provide. However, an impedance matching network between the resonator and its RF source is necessary, as an unmatched resonator would require higher input power due to power reflection. The reflected power would not contribute to the RF trapping potential, and the losses in the cable induce additional heat into the system. The electrical properties of the matching network components change during cooling, and a cryogenic setup usually prohibits physical access to integrated components while the experiment is running. This circumstance leads to either several cooling cycles to improve the matching at cryogenic temperatures or the operation of poorly matched resonators. In this work, we demonstrate an RF resonator that is actively matched to the wave impedance of coaxial cables and the signal source. The active part of the matching circuit consists of a varactor diode array. Its capacitance depends on the DC voltage applied from outside the cryostat. We present measurements of the power reflection, the Q-factor, and higher harmonic signals resulting from the nonlinearity of the varactor diodes. The RF resonator is tested in a cryostat at room temperature and cryogenic temperatures, down to 4.3 K. A superior impedance matching for different ion traps can be achieved with this type of resonator

    siRNA Screening of a Targeted Library of DNA Repair Factors in HIV Infection Reveals a Role for Base Excision Repair in HIV Integration

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    Host DNA repair enzymes have long been assumed to play a role in HIV replication, and many different DNA repair factors have been associated with HIV. In order to identify DNA repair pathways required for HIV infection, we conducted a targeted siRNA screen using 232 siRNA pools for genes associated with DNA repair. Mapping the genes targeted by effective siRNA pools to well-defined DNA repair pathways revealed that many of the siRNAs targeting enzymes associated with the short patch base excision repair (BER) pathway reduced HIV infection. For six siRNA pools targeting BER enzymes, the negative effect of mRNA knockdown was rescued by expression of the corresponding cDNA, validating the importance of the gene in HIV replication. Additionally, mouse embryo fibroblasts (MEFs) lacking expression of specific BER enzymes had decreased transduction by HIV-based retroviral vectors. Examining the role BER enzymes play in HIV infection suggests a role for the BER pathway in HIV integration

    Efficient and Specific Internal Cleavage of a Retroviral Palindromic DNA Sequence by Tetrameric HIV-1 Integrase

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    BACKGROUND: HIV-1 integrase (IN) catalyses the retroviral integration process, removing two nucleotides from each long terminal repeat and inserting the processed viral DNA into the target DNA. It is widely assumed that the strand transfer step has no sequence specificity. However, recently, it has been reported by several groups that integration sites display a preference for palindromic sequences, suggesting that a symmetry in the target DNA may stabilise the tetrameric organisation of IN in the synaptic complex. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the ability of several palindrome-containing sequences to organise tetrameric IN and investigated the ability of IN to catalyse DNA cleavage at internal positions. Only one palindromic sequence was successfully cleaved by IN. Interestingly, this symmetrical sequence corresponded to the 2-LTR junction of retroviral DNA circles-a palindrome similar but not identical to the consensus sequence found at integration sites. This reaction depended strictly on the cognate retroviral sequence of IN and required a full-length wild-type IN. Furthermore, the oligomeric state of IN responsible for this cleavage differed from that involved in the 3'-processing reaction. Palindromic cleavage strictly required the tetrameric form, whereas 3'-processing was efficiently catalysed by a dimer. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that the restriction-like cleavage of palindromic sequences may be a general physiological activity of retroviral INs and that IN tetramerisation is strongly favoured by DNA symmetry, either at the target site for the concerted integration or when the DNA contains the 2-LTR junction in the case of the palindromic internal cleavage

    Host Cell Factors in HIV Replication: Meta-Analysis of Genome-Wide Studies

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    We have analyzed host cell genes linked to HIV replication that were identified in nine genome-wide studies, including three independent siRNA screens. Overlaps among the siRNA screens were very modest (<7% for any pairwise combination), and similarly, only modest overlaps were seen in pairwise comparisons with other types of genome-wide studies. Combining all genes from the genome-wide studies together with genes reported in the literature to affect HIV yields 2,410 protein-coding genes, or fully 9.5% of all human genes (though of course some of these are false positive calls). Here we report an “encyclopedia” of all overlaps between studies (available at http://www.hostpathogen.org), which yielded a more extensively corroborated set of host factors assisting HIV replication. We used these genes to calculate refined networks that specify cellular subsystems recruited by HIV to assist in replication, and present additional analysis specifying host cell genes that are attractive as potential therapeutic targets

    Ancient and Recent Adaptive Evolution of Primate Non-Homologous End Joining Genes

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    In human cells, DNA double-strand breaks are repaired primarily by the non-homologous end joining (NHEJ) pathway. Given their critical nature, we expected NHEJ proteins to be evolutionarily conserved, with relatively little sequence change over time. Here, we report that while critical domains of these proteins are conserved as expected, the sequence of NHEJ proteins has also been shaped by recurrent positive selection, leading to rapid sequence evolution in other protein domains. In order to characterize the molecular evolution of the human NHEJ pathway, we generated large simian primate sequence datasets for NHEJ genes. Codon-based models of gene evolution yielded statistical support for the recurrent positive selection of five NHEJ genes during primate evolution: XRCC4, NBS1, Artemis, POLλ, and CtIP. Analysis of human polymorphism data using the composite of multiple signals (CMS) test revealed that XRCC4 has also been subjected to positive selection in modern humans. Crystal structures are available for XRCC4, Nbs1, and Polλ; and residues under positive selection fall exclusively on the surfaces of these proteins. Despite the positive selection of such residues, biochemical experiments with variants of one positively selected site in Nbs1 confirm that functions necessary for DNA repair and checkpoint signaling have been conserved. However, many viruses interact with the proteins of the NHEJ pathway as part of their infectious lifecycle. We propose that an ongoing evolutionary arms race between viruses and NHEJ genes may be driving the surprisingly rapid evolution of these critical genes
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