b tagging in ATLAS and CMS

Many physics signals presently studied at the high energy collision experiments lead to final states with jets originating from heavy flavor quarks. This report reviews the algorithms for heavy flavor jets identification developed by the ATLAS and CMS Collaborations in view of the Run2 data taking period at the Large Hadron Collider. The improvements of the algorithms used in 2015 and 2016 data analyses with respect to previous data taking periods are discussed, as well as the ongoing developments in view of the next years of data taking. The measurements of the performance of the algorithms on data as well as the dedicated techniques for the identification of heavy flavor jets in events with boosted topologies are also presented. Finally, the effectiveness of heavy flavor jet identification in the complex environment expected during the high luminosity LHC phase is discussed.Comment: 6 pages, Proceeding for the Fifth Annual Large Hadron Collider Physics (LHCP2017) conferenc

Sequences of trivalent SLPs including SART3_734-742.

<p>Sequences of trivalent SLPs including SART3_734-742.</p

Hematoxylin-eosin staining of <i>Tg</i><i>(</i><i>tyr:HRAS^G12V</i><i>)</i>/<i>Tg</i><i>(</i><i>hsp:cre</i><i>)</i> medaka.

<p>(<b>A</b>) Overall image of fish #7 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054424#pone-0054424-g003" target="_blank">Figure 3</a>. (<b>B</b>)– (<b>E</b>), Melanophore layers (arrows) of a wild-type adult fish (<b>B</b>) as well as of fish #7 (<b>C</b>), #6 (<b>D</b>), and #4 (<b>E</b>) in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054424#pone-0054424-g003" target="_blank">Figure 3</a>. (<b>F</b>)– (<b>J</b>), Eye, bone and spinal cord, heart, muscle, and gill, respectively, of fish #7 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054424#pone-0054424-g003" target="_blank">Figure 3</a>. (<b>K</b>) Enlarged image of the boxed region in (<b>J</b>). (<b>L</b>) Kidney and digestive duct of fish #7 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054424#pone-0054424-g003" target="_blank">Figure 3</a>. (<b>M</b>) Enlarged image of the boxed region in (<b>L</b>). Scale bars: 1 mm (<b>A</b>) and 0.1 mm (<b>B</b>–<b>M</b>).</p

Development of a novel immunoproteasome digestion assay for synthetic long peptide vaccine design

<div><p>Recently, many autologous tumor antigens have been examined for their potential use in cancer immunotherapy. However, the success of cancer vaccines in clinical trials has been limited, partly because of the limitations of using single, short peptides in most attempts. With this in mind, we aimed to develop multivalent synthetic long peptide (SLP) vaccines containing multiple cytotoxic T-lymphocyte (CTL) epitopes. However, to confirm whether a multivalent vaccine can induce an individual epitope-specific CTL, the only viable screening strategies currently available are interferon-gamma (IFN-μ enzyme-linked immunospot (ELISPOT) assays using human peripheral blood mononuclear cells, or expensive human leukocyte antigen (HLA)-expressing mice. In this report, we evaluated the use of our developed murine-20S immunoproteasome (i20S) digestion assay, and found that it could predict the results of IFN-μ ELISPOT assays. Importantly, the murine-i20S digestion assay not only predicted CTL induction, but also antitumor activity in an HLA-expressing mouse model. We conclude that the murine-i20S digestion assay is an extremely useful tool for the development of “all functional” multivalent SLP vaccines.</p></div

Sequences of multivalent peptides.

<p>Sequences of multivalent peptides.</p

Establishment of <em>HRAS</em> Transgenic Medaka as a Stable Tumor Model for <em>In Vivo</em> Screening of Anticancer Drugs

<div><p>Most targeted anticancer drugs have been identified by screening at the molecular or cellular level <em>in vitro</em>. However, many compounds selected by such costly and time-consuming screening do not prove effective against tumors <em>in vivo</em>. The development of anticancer drugs would thus be facilitated by the availability of an <em>in vivo</em> screening system based on a multicellular organism. We have now established a transgenic line of the freshwater fish medaka in which melanophores (melanocytes) proliferate in a manner dependent on heat shock–induced signaling by a human RAS oncoprotein. The human <em>HRAS^G12V</em> oncogene was expressed under the control of a melanophore-specific gene promoter in order to allow visualization of tumor growth in live fish maintained in a water tank. The expression of <em>HRAS^G12V</em> was induced as a result of Cre-mediated recombination by exposure of the fish to a temperature of 37°C for 30 min, given that the Cre gene was placed under the control of a medaka heat shock promoter. One of the stable transgenic lines developed abnormal pigment cell proliferation in the eyes and epidermis with 100% penetrance by 6 months postfertilization. Sorafenib, an inhibitor of RAS signaling, was administered to the transgenic fish and was found both to reduce the extent of melanophore proliferation and to improve survival. The transgenic medaka established here thus represents a promising <em>in vivo</em> system with which to screen potential anticancer drugs that target RAS signaling, and this system can readily be adapted for the screening of agents that target other oncogenes.</p> </div

Antitumor efficacy of multivalent SLP vaccines in the syngeneic tumor mouse model.

<p><i>HLA-A24</i> KI mice (n = 10) were subcutaneously treated with distilled water (control), SART2_93-101 or multivalent SLPs that were emulsified with Montanide ISA-51VG. Seven days after the final vaccination, B16F10.A24/SART2_93-101 cells (5 × 10⁶ cells) were subcutaneously engrafted into vaccinated mice. Tumor sizes were monitored with calipers, twice per week. Data are presented as mean tumor volume ± s.d.; * Student’s t-test, p < 0.05 vs. control group.</p

Comparison between the murine-i20S digestion assay and specific CTL induction using HLA-expressing mice.

<p>(a)-(f) The digestion maps of trivalent SLP fragments after 1, 2, or 4 h (highlighted in purple, green, or red, respectively). Epitope-related fragments are outlined in bold. (g)-(l) Results of IFN-γ ELISPOT in trivalent SLP-treated mice. Data represent mean ± s.d. (n = 3–4); open bars, target epitope peptide stimulation; closed bars, negative control peptide stimulation; * Student’s t-test, p < 0.05. (m) IFN-γ ELISPOT results in each short epitope peptide-treated mice. (n) Comparison of the results between CTL induction and the murine-i20S digestion assay. CTL-induced epitopes are colored in dark grey, and i20S digested epitopes are colored in purple, green or red, based on their first detected time-point i.e. 1, 2, or 4 h, respectively.</p

Effect of sorafenib (0.1 μM) treatment on melanophore hyperplasia and overall survival in <i>Tg</i><i>(</i><i>tyr:HRAS^G12V</i><i>)</i><i>/Tg</i><i>(</i><i>hsp:cre</i><i>)</i> medaka.

<p>(<b>A</b>) Schedule of drug administration. (<b>B</b>) Photos taken from the dorsal side of all fish at 7 days before (day –7) and 29 days after (day +29) the first drug administration. The area of MPLs in the fish body was measured based on the set of captured images on the right, and the average fold change from day –7 to day +29 was calculated for each group. (<b>C</b>) Kaplan-Meier survival curves for the sorafenib-treated and control (DMSO-treated) groups were generated from the experiment shown in (<b>B</b>). Fish with obvious melanophore hyperplasia were divided into two groups, one of which was treated with 0.1 μM sorafenib (<i>n</i> = 14) and the other with DMSO as a control (<i>n</i> = 13). *<i>P</i> = 0.0267 (log-rank test).</p

Characteristics of <i>Tg</i><i>(</i><i>tyr:HRAS^G12V</i><i>)</i>/<i>Tg</i><i>(</i><i>hsp:cre</i><i>)</i> medaka.

<p>Age-dependent changes in eight double-transgenic fish were monitored after heat treatment at 1 wpf. Five of the eight fish manifested hyperproliferation of pigment cells around the eyes by 8 wpf. All of the fish had developed MPLs with characteristics of infiltrative tumors by 20 wpf, and all had died by 43 wpf. Arrows indicate the first appearance of metastasis-like lesions.</p