Predicting Antigen Presentation-What Could We Learn From a Million Peptides?

Antigen presentation lies at the heart of immune recognition of infected or malignant cells. For this reason, important efforts have been made to predict which peptides are more likely to bind and be presented by the human leukocyte antigen (HLA) complex at the surface of cells. These predictions have become even more important with the advent of next-generation sequencing technologies that enable researchers and clinicians to rapidly determine the sequences of pathogens (and their multiple variants) or identify non-synonymous genetic alterations in cancer cells. Here, we review recent advances in predicting HLA binding and antigen presentation in human cells. We argue that the very large amount of high-quality mass spectrometry data of eluted (mainly self) HLA ligands generated in the last few years provides unprecedented opportunities to improve our ability to predict antigen presentation and learn new properties of HLA molecules, as demonstrated in many recent studies of naturally presented HLA-I ligands. Although major challenges still lie on the road toward the ultimate goal of predicting immunogenicity, these experimental and computational developments will facilitate screening of putative epitopes, which may eventually help decipher the rules governing T cell recognition

A Functional Elaboration Theory Perspective on Management Accounting in Small Firms

We note a lack of theoretical explanations in a recent review of small-firm management accounting research and draw on recent organizational research (functional elaboration theory and theory of asymmetric effects of misfit, specifically) that may further illuminate findings in some small-firm management accounting studies. After briefly discussing how the functional elaboration process model in Wilkerson and Seers (2019) may be adapted to small-firm management accounting research, we offer recommendations for questionnaire measures of management accounting’s qualitative functional elaboration and underfit in small firms. Finally, we discuss implications for practice and entrepreneurship education

Quantum-kinetic theory of photocurrent generation via direct and phonon-mediated optical transitions

A quantum-kinetic theory of direct and phonon mediated indirect optical transitions is developed within the framework of the non-equilibrium Green's function formalism. After validation against the standard Fermi-Golden-Rule approach in the bulk case, it is used in the simulation of photocurrent generation in ultra-thin crystalline silicon p-i-n-junction devices.Comment: 12 pages, 11 figure

Fading of the Transient Anomalous X-ray Pulsar XTE J1810-197

Three observations of the 5.54 s Transient Anomalous X-ray Pulsar XTE J1810-197 obtained over 6 months with the Newton X-Ray Multi-Mirror Mission (XMM-Newton) are used to study its spectrum and pulsed light curve as the source fades from outburst. The decay is consistent with an exponential of time constant 300 days, but not a power law as predicted in some models of sudden deep crustal heating events. All spectra are well fitted by a blackbody plus a steep power law, a problematic model that is commonly fitted to anomalous X-ray pulsars (AXPs). A two-temperature blackbody fit is also acceptable, and better motivated physically in view of the faint optical/IR fluxes, the X-ray pulse shapes that weakly depend on energy in XTE J1810-197, and the inferred emitting areas that are less than or equal to the surface area of a neutron star. The fitted temperatures remained the same while the flux declined by 46%, which can be interpreted as a decrease in area of the emitting regions. The pulsar continues to spin down, albeit at a reduced rate of (5.1+/-1.6)x10^{-12} s s^{-1}. The inferred characteristic age Tau_c = P/2Pdot ~17,000 yr, magnetic field strength B_s ~1.7x10^{14} G, and outburst properties are consistent with both the outburst and quiescent X-ray luminosities being powered by magnetic field decay, i.e., XTE J1810-197 is a magnetar.Comment: 10 pages, 5 figures, accepted by Ap.

'Hotspots' of Antigen Presentation Revealed by Human Leukocyte Antigen Ligandomics for Neoantigen Prioritization.

The remarkable clinical efficacy of the immune checkpoint blockade therapies has motivated researchers to discover immunogenic epitopes and exploit them for personalized vaccines. Human leukocyte antigen (HLA)-binding peptides derived from processing and presentation of mutated proteins are one of the leading targets for T-cell recognition of cancer cells. Currently, most studies attempt to identify neoantigens based on predicted affinity to HLA molecules, but the performance of such prediction algorithms is rather poor for rare HLA class I alleles and for HLA class II. Direct identification of neoantigens by mass spectrometry (MS) is becoming feasible; however, it is not yet applicable to most patients and lacks sensitivity. In an attempt to capitalize on existing immunopeptidomics data and extract information that could complement HLA-binding prediction, we first compiled a large HLA class I and class II immunopeptidomics database across dozens of cell types and HLA allotypes and detected hotspots that are subsequences of proteins frequently presented. About 3% of the peptidome was detected in both class I and class II. Based on the gene ontology of their source proteins and the peptide's length, we propose that their processing may partake by the cellular class II presentation machinery. Our database captures the global nature of the in vivo peptidome averaged over many HLA alleles, and therefore, reflects the propensity of peptides to be presented on HLA complexes, which is complementary to the existing neoantigen prediction features such as binding affinity and stability or RNA abundance. We further introduce two immunopeptidomics MS-based features to guide prioritization of neoantigens: the number of peptides matching a protein in our database and the overlap of the predicted wild-type peptide with other peptides in our database. We show as a proof of concept that our immunopeptidomics MS-based features improved neoantigen prioritization by up to 50%. Overall, our work shows that, in addition to providing huge training data to improve the HLA binding prediction, immunopeptidomics also captures other aspects of the natural in vivo presentation that significantly improve prediction of clinically relevant neoantigens

Life cycle economic and environmental impacts of cdw recycled aggregates in roadway construction and rehabilitation

The use of recycled materials in roadway construction and rehabilitation can achieve significant benefits in saving natural resources, reducing energy, greenhouse gas emissions and costs. Construction and demolition waste (CDW) recycled aggregate as an alternative to natural one can enhance sustainability benefits in roadway infrastructure. The objective of this study was to quantitatively assess the life cycle economic and environmental benefits when alternative stabilizedCDW aggregates are used in pavement construction. Comparative analysis was conducted on a pavement project representative of typical construction practices in northern Italy so as to quantify such benefits. The proposed alternative sustainable construction strategies considered CDW aggregates stabilized with both cement and cement kiln dust (CKD) for the base layer of the roadway. The life cycle assessment results indicate that using CDW aggregate stabilized with CKD results in considerable cost savings and environmental benefits due to (i) lower energy consumption and emissions generation during material processing and (ii) reduction in landfill disposal. The benefits illustrated in this analysis should encourage the wider adoption of stabilized CDW aggregate in roadway construction and rehabilitation. In terms of transferability, the analysis approach suggested in this study can be used to assess the economic and environmental benefits of these and other recycled materials in roadway infrastructure elsewhere

Caracterização de resíduos sólidos de coleta seletiva em condomínios residenciais Estudo de Caso em Vitória - ES.

A caracterização, identificação e quantificação de resíduos sólidos é de grande importância para a elaboração dos planos de gerenciamento de resídos sólidos. Os condomínios residenciais verticalizados merecem destaque no gerenciamento, pois constituem uma importante fonte de geração de resíduos sólidos, em grande escala. Assim, o presente trabalho teve como objetivo realizar a caracterização física dos resíduos sólidos de coleta seletiva de condomínios residenciais verticalizados da cidade de Vitória ES. Foram realizados levantamentos de dados, ensaios de caracterização física dos resíduos e avaliados os resultados com relação à participação, à receita da venda dos recicláveis, à operacionalidade do programa e à redução de resíduos encaminhados ao aterro sanitário. O valor per capita médio de lixo seco encontrado foi de 0,069 kg/hab/dia. Dentre os materiais segregados o que obteve maior quantidade em peso e volume foi o papel e os menos observados foram os REEE. O papel apresentou percentual gravimétrico acima da média nacional. Os demais materiais ficaram abaixo da média do país. Não foi observado comportamento padrão semanal na geração dos resíduos, nem encontrada correlação entre o tempo de existência do programa de coleta seletiva e o valor per capita observado. Observou-se alta correlação negativa entre a geração per capita e o número de apartamentos nos condomínios, sugerindo-se que condomínios com maior número de residências têm dificuldades de disseminar a coleta seletiva em todos os apartamentos, levando a índices menores de participação. O peso específico aparente médio observado para os resíduos sólidos secos foi de 68,04 kg/m3, com rejeitos, e 62,58 kg/m3, sem rejeitos. O IRMR obtido foi de 6,53%, valor considerado médio, e o percentual de participação estimado em 19,93%. A receita potencial gerada a partir da venda dos recicláveis foi de mais de 120 mil reais por mês, garantindo a sustentabilidade econômica das associações de catadores. Detectou-se a possibilidade de ajustes na freqüência de coleta para minimizar os custos do serviço. A transferência de resíduos para associações de catadores poderia ser aumentada em 293 vezes, e tem potencial de redução de mais de 5% dos resíduos do município encaminhados a aterros sanitários

BATSE Observations of the Piccinotti Sample of AGN

BATSE Earth occultation data have been used to search for emission in the 20-100 keV band from all sources in the Piccinotti sample, which represents to date the only complete 2-10 keV survey of the extragalactic sky down to a limiting flux of 3.1 x 10^(-11) erg cm^(-2)$ s^(-1). Nearly four years of observations have been analyzed to reach a 5sigma sensitivity level of about 7.8x 10^(-11) erg cm^(-2) s^(-1) in the band considered. Of the 36 sources in the sample, 14 have been detected above 5sigma confidence level while marginal detection (3<sigma<5) can be claimed for 13 sources; for 9 objects 2sigma upper limits are reported. Comparison of BATSE results with data at higher energies is used to estimate the robustness of our data analysis: while the detection level of each source is reliable, the flux measurement maybe overestimated in some sources by as much as 35%, probably due to incomplete data cleaning. Comparison of BATSE fluxes with X-ray fluxes, obtained in the 2-10 keV range and averaged over years, indicates that a canonical power law of photon index 1.7 gives a good description of the broad band spectra of bright AGNs and that spectral breaks preferentially occur above 100 keV.Comment: 18 pages, 1 figure. Accepted for publication on Apj

Engineering Silicon Nanocrystals: Theoretical study of the effect of Codoping with Boron and Phosphorus

We show that the optical and electronic properties of nanocrystalline silicon can be efficiently tuned using impurity doping. In particular, we give evidence, by means of ab-initio calculations, that by properly controlling the doping with either one or two atomic species, a significant modification of both the absorption and the emission of light can be achieved. We have considered impurities, either boron or phosphorous (doping) or both (codoping), located at different substitutional sites of silicon nanocrystals with size ranging from 1.1 nm to 1.8 nm in diameter. We have found that the codoped nanocrystals have the lowest impurity formation energies when the two impurities occupy nearest neighbor sites near the surface. In addition, such systems present band-edge states localized on the impurities giving rise to a red-shift of the absorption thresholds with respect to that of undoped nanocrystals. Our detailed theoretical analysis shows that the creation of an electron-hole pair due to light absorption determines a geometry distortion that in turn results in a Stokes shift between adsorption and emission spectra. In order to give a deeper insight in this effect, in one case we have calculated the absorption and emission spectra going beyond the single-particle approach showing the important role played by many-body effects. The entire set of results we have collected in this work give a strong indication that with the doping it is possible to tune the optical properties of silicon nanocrystals.Comment: 14 pages 19 figure

Swift-XRT observation of 34 new INTEGRAL/IBIS AGNs: discovery of Compton thick and other peculiar sources

For a significant number of the sources detected at high energies (>10 keV) by the INTEGRAL/IBIS and Swift/BAT instruments there is either a lack information about them in the 2-10 keV range or they are totally unidentified. Herein, we report on a sample of 34 IBIS AGN or AGN candidate objects for which there is X-ray data in the Swift/XRT archive. Thanks to these X-ray follow up observations, the identification of the gamma ray emitters has been possible and the spectral shape in terms of photon index and absorption has been evaluated for the first time for the majority of our sample sources. The sample, enlarged to include 4 more AGN already discussed in the literature, has been used to provide photon index and column density distribution. We obtain a mean value of 1.88 with a dispersion of 0.12, i.e. typical of an AGN sample. Sixteen objects (47%) have column densities in excess of 10^{22} cm^{-2} and, as expected, a large fraction of the absorbed sources are within the Sey 2 sample. We have provided a new diagnostic tool (NH versus F(2-10)keV/F(20-100)keV softness ratio) to isolate peculiar objects; we find at least one absorbed Sey 1 galaxy, 3 Compton thick AGN candidates; and one secure example of a "true" type 2 AGN. Within the sample of 10 still unidentified objects, 3 are almost certainly AGN of type 2; 3 to 4 have spectral slopes typical of AGN; and two are located high on the galactic plane and are strong enough radio emitters so that can be considered good AGN candidates.Comment: 15 pages, 5 figures, ApJ accepte