The Detail Behind Web-Scale: Selecting and Configuring Web-Scale Discovery Tools to Meet Music Information Retrieval Needs.

Web-scale discovery tools are rapidly gaining popularity as a purported "one-stop search" for discovering library information. Music, particularly printed music and recordings, presents unique information retrieval needs. This article identifies, explores, and makes recommendations regarding key music-related aspects to consider when selecting and implementing a discovery tool, considering scope, metadata, and interface

The ABC130 barrel module prototyping programme for the ATLAS strip tracker

For the Phase-II Upgrade of the ATLAS Detector, its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100 % silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-25) and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.Comment: 82 pages, 66 figure

DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity

Contains fulltext : 118242.pdf (publisher's version ) (Open Access)BACKGROUND: Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. METHODOLOGY/PRINCIPAL FINDINGS: The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44-817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5-102) and were not associated with protection. Ex vivo IFN-gamma ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13-408; AMA1 348, range 88-1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-gamma mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. SIGNIFICANCE: The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection. TRIAL REGISTRATION: ClinicalTrials.govNCT00870987

Trial design.

<p>Subjects were immunized week 0, 4, 8 and 24 and challenged week 28 (blue arrows). Samples for measuring cell-mediated immunity (ELISpot assay and flow cytometry) were collected at six time points (black arrows), and for measuring antibody levels (ELISA, IFA and growth inhibition assay) at similar time points plus after the DNA immunizations (gray arrows). See text for details.</p

Development of parasitemia in the immunized and infectivity control subjects.

<p><b>Panel A</b>: Parasitemia-free survival curves (Kaplan-Meier) for immunized volunteers and infectivity controls based on microscopic examination of peripheral blood smears. <b>Panel B</b>: Quantitative(q)-PCR measurements of parasitemia in immunized and challenge controls (error bars show standard deviation) (see reference 28).</p

Study subjects demographics.

<p>Twenty volunteers were enrolled into the immunization group; five dropped out prior to CHMI (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055571#pone-0055571-g003" target="_blank">Figure 3</a>). Infectivity controls were enrolled later, in time for CHMI on week 28. NAb titers are provided for the 15 study subjects who were challenged (included in the immunogenicity analysis); these were measured just prior to Ad boost.</p

Flow diagram of immunized and control volunteers.

<p>Thirty-seven volunteers met all eligibility criteria and were allocated to the immunization group (n = 20) and infectivity controls (n = 6), and 11 were either alternates (n = 6) or not used. WBC = white blood count; DVT = deep venous thrombosis. See text for explanation.</p

Numbers of volunteers experiencing local, systemic and laboratory adverse events (days 0–7 post each immunization).

<p>All local AE’s were considered definitely related to immunization, all systemic AE’s were considered probably related to immunization, except for diarrhea that was possibly related, and all laboratory AE’s were considered possibly related to immunization, Solicited local and systemic adverse events were recorded on days 0, 1, 2 and 7 and laboratory tests were recorded on days 0, 2, 7 and 28 after each immunization. Severity classification for signs and symptoms: Gr1 = adverse event does not interfere with daily activities; Gr2 = interferes with but does not prevent daily activities; Gr3 = prevents daily activities. Severity classification for decreased platelets: Gr1 = 75,000/ul; decreased WBC: Gr1 = 3,000/ul; elevated WBC: Gr1 = >upper limit of normal, <15,000/ul; elevated ALT: Gr1 = >upper limit of normal, <3 times upper limit of normal; decreased Hb: Gr1 = 10.0 g/dL. All adverse events in the table are Gr1 (mild) unless noted otherwise.</p>1<p> = Gr2 (moderate);</p>2<p> = Gr3 (severe). All local adverse events occurred in the arm ipsilateral to the injection site.</p

Antibody responses by ELISA to CSP and AMA1.

<p>The box plots (see Statistical Analysis section for description) represent anti-CSP titers and anti-AMA1 antibody concentration in µg/mL by ELISA for all 15 challenged volunteers. The time points on the x-axis are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055571#pone-0055571-g001" target="_blank">Figure 1</a>. Four protected volunteers are shown as larger, color-coded dots. For the protected volunteers, the antibody titer to CSP of v11 post-DNA and the antibody concentration to AMA1 of v11 post-Ad are box plot outliers. Group geomean CSP and AMA1 ELISA activities for the fifteen recipients were significantly higher than baseline (*) post-DNA, post-Ad, post-Ch and post-Ch final relative to pre-immunization levels (p = <0.0001, mixed linear model).</p

Schematic of DNA and Adenovirus CSP and AMA1 vaccines.

<p>Each panel presents the native protein (top of each panel) and the protein expressed by the DNA or Ad construct (middle and bottom of each panel) for the CSP (Panel <b>A</b>) and AMA1 (Panel <b>B</b>) vaccine antigens. N = amino terminus; C = carboxy terminus; TPA = human tissue plasminogen activator signal sequence; TM = transmembrane domain. See text for explanation. Identical colors indicate identical sequences. Not represented is a single amino acid substitution (G → R) in the AMA DNA construct at position 143.</p