Machine-learning prediction of tumor antigen immunogenicity in the selection of therapeutic epitopes

Current tumor neoantigen calling algorithms primarily rely on epitope/major histocompatibility complex (MHC) binding affinity predictions to rank and select for potential epitope targets. These algorithms do not predict for epitope immunogenicity using approaches modeled from tumor-specific antigen data. Here, we describe peptide-intrinsic biochemical features associated with neoantigen and minor histocompatibility mismatch antigen immunogenicity and present a gradient boosting algorithm for predicting tumor antigen immunogenicity. This algorithm was validated in two murine tumor models and demonstrated the capacity to select for therapeutically active antigens. Immune correlates of neoantigen immunogenicity were studied in a pan-cancer data set from The Cancer Genome Atlas and demonstrated an association between expression of immunogenic neoantigens and immunity in colon and lung adenocarcinomas. Lastly, we present evidence for expression of an out-of-frame neoantigen that was capable of driving antitumor cytotoxic T-cell responses. With the growing clinical importance of tumor vaccine therapies, our approach may allow for better selection of therapeutically relevant tumor-specific antigens, including nonclas-sic out-of-frame antigens capable of driving antitumor immunity

An evolutionarily-unique heterodimeric voltage-gated cation channel found in aphids

We describe the identification in aphids of a unique heterodimeric voltage-gated sodium channel which has an atypical ion selectivity filter and, unusually for insect channels, is highly insensitive to tetrodotoxin. We demonstrate that this channel has most likely arisen by adaptation (gene fission or duplication) of an invertebrate ancestral mono(hetero)meric channel. This is the only identifiable voltage-gated sodium channel homologue in the aphid genome(s), and the channel’s novel selectivity filter motif (DENS instead of the usual DEKA found in other eukaryotes) may result in a loss of sodium selectivity, as indicated experimentally in mutagenised Drosophila channels

Uncertainties of the CJK 5 Flavour LO Parton Distributions in the Real Photon

Radiatively generated, LO quark (u,d,s,c,b) and gluon densities in the real, unpolarized photon, calculated in the CJK model being an improved realization of the CJKL approach, have been recently presented. The results were obtained through a global fit to the experimental F2^gamma data. In this paper we present, obtained for the very first time in the photon case, an estimate of the uncertainties of the CJK parton distributions due to the experimental errors. The analysis is based on the Hessian method which was recently applied in the proton parton structure analysis. Sets of test parametrizations are given for the CJK model. They allow for calculation of its best fit parton distributions along with F2^gamma and for computation of uncertainties of any physical value depending on the real photon parton densities. We test the applicability of the approach by comparing uncertainties of example cross-sections calculated in the Hessian and Lagrange methods. Moreover, we present a detailed analysis of the chi^2 of the CJK fit and its relation to the data. We show that large chi^2/DOF of the fit is due to only a few of the experimental measurements. By excluding them chi^2/DOF approx 1 can be obtained.Comment: 28 pages, 8 eps figures, 2 Latex figures; FORTRAN programs available at http://www.fuw.edu.pl/~pjank/param.html; table 10, figure 10 and section 6 correcte

The Frequency Dependence of Critical-velocity Behavior in Oscillatory Flow of Superfluid Helium-4 Through a 2-micrometer by 2-micrometer Aperture in a Thin Foil

The critical-velocity behavior of oscillatory superfluid Helium-4 flow through a 2-micrometer by 2-micrometer aperture in a 0.1-micrometer-thick foil has been studied from 0.36 K to 2.10 K at frequencies from less than 50 Hz up to above 1880 Hz. The pressure remained less than 0.5 bar. In early runs during which the frequency remained below 400 Hz, the critical velocity was a nearly-linearly decreasing function of increasing temperature throughout the region of temperature studied. In runs at the lowest frequencies, isolated 2 Pi phase slips could be observed at the onset of dissipation. In runs with frequencies higher than 400 Hz, downward curvature was observed in the decrease of critical velocity with increasing temperature. In addition, above 500 Hz an alteration in supercritical behavior was seen at the lower temperatures, involving the appearance of large energy-loss events. These irregular events typically lasted a few tens of half-cycles of oscillation and could involve hundreds of times more energy loss than would have occurred in a single complete 2 Pi phase slip at maximum flow. The temperatures at which this altered behavior was observed rose with frequency, from ~ 0.6 K and below, at 500 Hz, to ~ 1.0 K and below, at 1880 Hz.Comment: 35 pages, 13 figures, prequel to cond-mat/050203

Guidebook for the sixteenth annual field conference of the Tri-State Geological Society / Illinois State Geological Survey guidebook series, vol. 2

Cover title."Illinois, Iowa, Wisconsin - 1933"--Cover."October 11 and 12, 1952."Includes bibliographical references (l. 9)

Modeling of Photoionized Plasmas

In this paper I review the motivation and current status of modeling of plasmas exposed to strong radiation fields, as it applies to the study of cosmic X-ray sources. This includes some of the astrophysical issues which can be addressed, the ingredients for the models, the current computational tools, the limitations imposed by currently available atomic data, and the validity of some of the standard assumptions. I will also discuss ideas for the future: challenges associated with future missions, opportunities presented by improved computers, and goals for atomic data collection.Comment: 17 pages, 8 figures, to appear in the proceedings of Xray2010, Utrecht, the Netherlands, March 15-17 201

Paying for treatments? Influences on negotiating clinical need and decision-making for dental implant treatment

Background The aim of this study is to examine how clinicians and patients negotiate clinical need and treatment decisions within a context of finite resources. Dental implant treatment is an effective treatment for missing teeth, but is only available via the NHS in some specific clinical circumstances. The majority of people who receive this treatment therefore pay privately, often at substantial cost to themselves. People are used to paying towards dental treatment costs. However, dental implant treatment is much more expensive than existing treatments – such as removable dentures. We know very little about how dentists make decisions about whether to offer such treatments, or what patients consider when deciding whether or not to pay for them. Methods/Design Mixed methods will be employed to provide insight and understanding into how clinical need is determined, and what influences people's decision making processes when deciding whether or not to pursue a dental implant treatment. Phase 1 will use a structured scoping questionnaire with all the General dental practitioners (GDPs) in three Primary Care Trust areas (n = 300) to provide base-line data about existing practice in relation to dental implant treatment, and to provide data to develop a systematic sampling procedure for Phase 2. Phases 2 (GDPs) and 3 (patients) use qualitative focused one to one interviews with a sample of these practitioners (up to 30) and their patients (up to 60) to examine their views and experiences of decision making in relation to dental implant treatment. Purposive sampling for phases 2 and 3 will be carried out to ensure participants represent a range of socio-economic circumstances, and choices made. Discussion Most dental implant treatment is conducted in primary care. Very little information was available prior to this study about the quantity and type of treatment carried out privately. It became apparent during phase 2 that ISOD treatment was an unusual treatment in primary care. We thus extended our sample criteria for Phase 3 to include people who had had other implant supported restorations, although not single tooth replacements

Ion-beam-induced reconstruction of amorphous GaN

Wurtzite GaN can be rendered amorphous by high-dose heavy-ion bombardment. We show here that relatively low-dose reirradiation of such amorphous GaN (a-GaN) with MeV light ions can significantly change some of the physical properties of a-GaN. In particular, light-ion reirradiation of a-GaN results in (i) an increase in material density, (ii) the suppression of complete decomposition during postimplantation annealing, (iii) a significant increase in the values of hardness and Young's modulus, and (iv) an apparent decrease in the absorption of visible light. Transmission electronmicroscopy shows that a-GaN remains completely amorphous after light-ion reirradiation. Therefore, we attribute the above effects of light-ion reirradiation to an ion-beam-induced atomic-level reconstruction of the amorphous phase. Results indicate that electronic energy loss of light ions is responsible for the changes in the mechanical properties and for the suppression of thermally induced decomposition of a-GaN. However, the changes in the density of a-GaN appear to be controlled by the nuclear energy loss of light ions

Grain Destruction in Interstellar Shocks

Interstellar shock waves can erode and destroy grains present in the shocked gas, primarily as the result of sputtering and grain-grain collisions. Uncertainties in current estimates of sputtering yields are reviewed. Results are presented for the simple case of sputtering of fast grains being stopped in cold gas. An upper limit is derived for sputtering of refractory grains in C-type MHD shocks: shock speeds v_s \gtrsim 50 \kms are required for return of more than 30\% of the silicate to the gas phase. Sputtering can also be important for removing molecular ice mantles from grains in two-fluid MHD shock waves in molecular gas. Recent estimates of refractory grain lifetimes against destruction in shock waves are summarized, and the implications of these short lifetimes are discussed.Comment: To appear in Shocks in Astrophysics, ed. T.J. Millar. Talk given at conference Shocks in Astrophysics, Manchester, Jan. 1995. 13 pages with 6 figures: uuencoded compressed postscript. Also available as POPe-633 on http://astro.princeton.edu/~library/prep.htm