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Significance Influenza A viruses (IAVs) are a cause of major morbidity in the human population. Being RNA viruses, replication is error prone, and proteins such as viral envelope hemagglutinin rapidly mutate. Current vaccines stimulate antibodies targeting exposed virion proteins but require annual reformation due to constant sequence variation. In contrast, vaccines that stimulate CD8 T cells directed at conserved peptides from internal proteins would offer stable immunity if these peptides are displayed by HLA proteins on infected cells. Currently, functional readouts infer the IAV peptides displayed. Using new MS technology, epitopes on infected human HLA-A2 ⁺ lung epithelium are identified and abundances characterized. The data show interconnections between viral evasion, immunodominance, and stealth responses that will aid in developing cellular vaccines against influenza. Vaccines eliciting immunity against influenza A viruses (IAVs) are currently antibody-based with hemagglutinin-directed antibody titer the only universally accepted immune correlate of protection. To investigate the disconnection between observed CD8 T-cell responses and immunity to IAV, we used a Poisson liquid chromatography data-independent acquisition MS method to physically detect PR8/34 (H1N1), X31 (H3N2), and Victoria/75 (H3N2) epitopes bound to HLA-A*02:01 on human epithelial cells following in vitro infection. Among 32 PR8 peptides (8–10mers) with predicted IC ₅₀ < 60 nM, 9 were present, whereas 23 were absent. At 18 h postinfection, epitope copies per cell varied from a low of 0.5 for M1 ₃–₁₁ to a high of >500 for M1 ₅₈–₆₆ with PA, HA, PB1, PB2, and NA epitopes also detected. However, aside from M1 ₅₈–₆₆, natural CD8 memory responses against conserved presented epitopes were either absent or only weakly observed by blood Elispot. Moreover, the functional avidities of the immunodominant M1 ₅₈–₆₆/HLA-A*02:01-specific T cells were so poor as to be unable to effectively recognize infected human epithelium. Analysis of T-cell responses to primary PR8 infection in HLA-A*02:01 transgenic B6 mice underscores the poor avidity of T cells recognizing M1 ₅₈–₆₆. By maintaining high levels of surface expression of this epitope on epithelial and dendritic cells, the virus exploits the combination of immunodominance and functional inadequacy to evade HLA-A*02:01-restricted T-cell immunity. A rational approach to CD8 vaccines must characterize processing and presentation of pathogen-derived epitopes as well as resultant immune responses. Correspondingly, vaccines may be directed against “stealth” epitopes, overriding viral chicanery.

The human CD1b protein presents lipid antigens to T cells, but the molecular mechanism is unknown. Identification of mycobacterial glucose monomycolate (GMM) as a CD1b-presented glycolipid allowed determination of the structural requirements for its recognition by T cells. Presentation of GMM to CD1b-restricted T cells was not affected by substantial variations in its lipid tails, but was extremely sensitive to chemical alterations in its carbohydrate or other polar substituents. These findings support the view that the recently demonstrated hydrophobic CD1 groove binds the acyl chains of lipid antigens relatively nonspecifically, thereby positioning the hydrophilic components for highly specific interactions with T cell antigen receptors.

A diverse group of soil bacteria known as plant growth promoting rhizobacteria (PGPR) is able to inhabit the area close to plant roots and exert beneficial effects on plant growth. Beneficial interactions between rhizospheric bacteria and plants provide prospects for isolating culturable PGPR that can be used as bio-fertilizers for sustainable crop production in communities that cannot easily afford chemical fertilizers. This study was conducted with the aim of isolating rhizospheric bacteria from grasses along the Kavango River and screening the bacterial isolates for plant growth promoting characteristics. The bacteria were isolated from rhizospheres of Phragmites australis, Sporobolus sp., Vetiveria nigritana, Pennisetum glaucum and Sorghum bicolor. The isolates were screened for inorganic phosphate solubilization, siderophore production and indole-3-acetic acid (IAA) production. The nitrogen-fixing capability of the bacteria was determined by screening for the presence of the nifH gene. Up to 21 isolates were obtained from P. australis, Sporobolus sp., S. bicolor, P. glaucum and V. nigritana. The genera Bacillus, Enterobacter, Kocuria, Pseudomonas and Stenotrophomonas, identified via 16S rDNA were represented in the 13 PGPR strains isolated. The isolates exhibited more than one plant growth promoting trait and they were profiled as follows: three phosphate solubilizers, four siderophore producers, eight IAA producing isolates and five nitrogen-fixers. These bacteria can be used to develop bio-fertilizer inoculants for improved soil fertility management and sustainable production of local cereals.

The Alaskan boreal forest is characterized by frequent extensive wildfires whose spatial extent has been mapped for the past 70 years. Simple predictions based on this record indicate that area burned will increase as a response to climate warming in Alaska. However, two additional factors have affected the area burned in this time record: the Pacific decadal oscillation (PDO) switched from cool and moist to warm and dry in the late 1970s and the Alaska Fire Service instituted a fire suppression policy in the late 1980s. In this paper a geographic information system (GIS) is used in combination with statistical analyses to reevaluate the changes in area burned through time in Alaska considering both the influence of the PDO and fire management. The authors found that the area burned has increased since the PDO switch and that fire management drastically decreased the area burned in highly suppressed zones. However, the temporal analysis of this study shows that the area burned is increasing more rapidly in suppressed zones than in the unsuppressed zone since the late 1980s. These results indicate that fire policies as well as regional climate patterns are important as large-scale controls on fires over time and across the Alaskan boreal forest.

. Building on the successful experience in operating the DarkSide-50 detector, the DarkSide Collaboration is going to construct DarkSide-20k, a direct WIMP search detector using a two-phase Liquid Argon Time Projection Chamber (LAr TPC) with an active (fiducial) mass of 23 t (20 t). This paper describes a preliminary design for the experiment, in which the DarkSide-20k LAr TPC is deployed within a shield/veto with a spherical Liquid Scintillator Veto (LSV) inside a cylindrical Water Cherenkov Veto (WCV). This preliminary design provides a baseline for the experiment to achieve its physics goals, while further development work will lead to the final optimization of the detector parameters and an eventual technical design. Operation of DarkSide-50 demonstrated a major reduction in the dominant 39 Ar background when using argon extracted from an underground source, before applying pulse shape analysis. Data from DarkSide-50, in combination with MC simulation and analytical modeling, shows that a rejection factor for discrimination between electron and nuclear recoils of > 3 × 10 9 is achievable. This, along with the use of the veto system and utilizing silicon photomultipliers in the LAr TPC, are the keys to unlocking the path to large LAr TPC detector masses, while maintaining an experiment in which less than < 0 . 1 events (other than ν -induced nuclear recoils) is expected to occur within the WIMP search region during the planned exposure. DarkSide-20k will have ultra-low backgrounds than can be measured in situ , giving sensitivity to WIMP-nucleon cross sections of 1 . 2 × 10 - 47 cm 2 ( 1 . 1 × 10 - 46 cm 2 ) for WIMPs of 1 TeV/c 2 (10 TeV/c 2 ) mass, to be achieved during a 5 yr run producing an exposure of 100 t yr free from any instrumental background.

Neutrinos were assumed to be massless particles until the discovery of the neutrino oscillation process. This phenomenon indicates that the neutrinos have non-zero masses and the mass eigenstates ( ν 1 , ν 2 , ν 3 ) are mixtures of their flavour eigenstates ( ν e , ν μ , ν τ ). The oscillations between different flavour eigenstates are described by three mixing angles ( θ 12 , θ 23 , θ 13 ), two differences of the squared neutrino masses of the ν 2 / ν 1 and ν 3 / ν 1 pairs and a charge conjugation parity symmetry violating phase δ CP . The Double Chooz experiment, located near the Chooz Electricité de France reactors, measures the oscillation parameter θ 13 using reactor neutrinos. Here, the Double Chooz collaboration reports the measurement of the mixing angle θ 13 with the new total neutron capture detection technique from the full data set, yielding sin 2 (2 θ 13 ) = 0.105 ± 0.014. This measurement exploits the multidetector configuration, the isoflux baseline and data recorded when the reactors were switched off. In addition to the neutrino mixing angle measurement, Double Chooz provides a precise measurement of the reactor neutrino flux, given by the mean cross-section per fission 〈 σ f 〉 = (5.71 ± 0.06) × 10 −43  cm 2 per fission, and reports an empirical model of the distortion in the reactor neutrino spectrum. The Double Chooz collaboration reports the neutrino oscillation parameter θ 13 from a measurement of the disappearance of reactor anti-electron neutrinos with the total neutron capture technique.

A bstract The Double Chooz experiment presents improved measurements of the neutrino mixing angle θ 13 using the data collected in 467.90 live days from a detector positioned at an average distance of 1050 m from two reactor cores at the Chooz nuclear power plant. Several novel techniques have been developed to achieve significant reductions of the backgrounds and systematic uncertainties with respect to previous publications, whereas the efficiency of the ν ¯ e signal has increased. The value of θ 13 is measured to be sin 2  2 θ 13  = 0.090 − 0.029 + 0.032 from a fit to the observed energy spectrum. Deviations from the reactor ν ¯ e prediction observed above a prompt signal energy of 4 MeV and possible explanations are also reported. A consistent value of θ 13 is obtained from a fit to the observed rate as a function of the reactor power independently of the spectrum shape and background estimation, demonstrating the robustness of the θ 13 measurement despite the observed distortion.

Tumor-infiltrating lymphocytes (TIL) are considered enriched for T cells recognizing shared tumor antigens or mutation-derived neoepitopes. We performed exome sequencing and HLA-A 02:01 epitope prediction from tumor cell lines from two HLA-A2-positive melanoma patients whose TIL displayed strong tumor reactivity. The potential neoepitopes were screened for recognition using autologous TIL by immunological assays and presentation on tumor major histocompatibility complex class I (MHC-I) molecules by Poisson detection mass spectrometry (MS). TIL from the patients recognized 5/181 and 3/49 of the predicted neoepitopes, respectively. MS screening detected 3/181 neoepitopes on tumor MHC-I from the first patient but only one was also among those recognized by TIL. Consequently, TIL enriched for neoepitope specificity failed to recognize tumor cells, despite being activated by peptides. For the second patient, only after IFN-γ treatment of the tumor cells was one of 49 predicted neoepitopes detected by MS, and this coincided with recognition by TIL sorted for the same specificity. Importantly, specific T cells could be expanded from patient and donor peripheral blood mononuclear cells (PBMC) for all neoepitopes recognized by TIL and/or detected on tumor MHC-I. In summary, stimulating the appropriate inflammatory environment within tumors may promote neoepitope MHC presentation while expanding T cells in blood may circumvent lack of specific TIL. The discordance in detection between physical and functional methods revealed here can be rationalized and used to improve neoantigen-targeted T cell immunotherapy.

We have established a differential peptide display method, based on a mass spectrometric technique, to detect peptides that show semiquantitative changes in the neurointermediate lobe (NIL) of individual rats subjected to salt-loading. We employed matrix-assisted laser desorption/ionization mass spectrometry, using a single-reference peptide in combination with careful scanning of the whole crystal rim of the matrix-analyte preparation, to detect in a semiquantitative manner the molecular ions present in the unfractionated NIL homogenate. Comparison of the mass spectra generated from NIL homogenates of salt-loaded and control rats revealed a selective and significant decrease in the intensities of several molecular ion species of the NIL homogenates from salt-loaded rats. These ion species, which have masses that correspond to the masses of oxytocin, vasopressin, neurophysins, and an unidentified putative peptide, were subsequently chemically characterized. We confirmed that the decreased molecular ion species are peptides derived exclusively from propressophysin and prooxyphysin (i.e., oxytocin, vasopressin, and various neurophysins). The putative peptide is carboxyl-terminal glycopeptide. The carbohydrate moiety of the latter peptide was determined by electrospray tandem MS as bisected biantennary Hex3HexNAc5Fuc. This posttranslational modification accounts for the mass difference between the predicted mass of the peptide based on cDNA studies and the measured mass of the mature peptide.

We present a search for signatures of neutrino mixing of electron anti-neutrinos with additional hypothetical sterile neutrino flavors using the Double Chooz experiment. The search is based on data from 5 years of operation of Double Chooz, including 2 years in the two-detector configuration. The analysis is based on a profile likelihood, i.e. comparing the data to the model prediction of disappearance in a data-to-data comparison of the two respective detectors. The analysis is optimized for a model of three active and one sterile neutrino. It is sensitive in the typical mass range 5×10-3eV2≲Δm412≲3×10-1eV2 for mixing angles down to sin22θ14≳0.02. No significant disappearance additionally to the conventional disappearance related to θ13 is observed and correspondingly exclusion bounds on the sterile mixing parameter θ14 as a function of Δm412 are obtained.