Fast-neutron induced background in LaBr3:Ce detectors

The response of a scintillation detector with a cylindrical 1.5-inch LaBr3:Ce crystal to incident neutrons has been measured in the energy range En = 2-12 MeV. Neutrons were produced by proton irradiation of a Li target at Ep = 5-14.6 MeV with pulsed proton beams. Using the time-of-flight information between target and detector, energy spectra of the LaBr3:Ce detector resulting from fast neutron interactions have been obtained at 4 different neutron energies. Neutron-induced gamma rays emitted by the LaBr3:Ce crystal were also measured in a nearby Ge detector at the lowest proton beam energy. In addition, we obtained data for neutron irradiation of a large-volume high-purity Ge detector and of a NE-213 liquid scintillator detector, both serving as monitor detectors in the experiment. Monte-Carlo type simulations for neutron interactions in the liquid scintillator, the Ge and LaBr3:Ce crystals have been performed and compared with measured data. Good agreement being obtained with the data, we present the results of simulations to predict the response of LaBr3:Ce detectors for a range of crystal sizes to neutron irradiation in the energy range En = 0.5-10 MeVComment: 28 pages, 10 figures, 4 Table

Monitoring of northern climate exposure

Currently, facility managers are faced with many advanced decisions regarding when and how to inspect, maintain, repair or renew existing facilities in a costeffective manner. The evolution of the deteriorations of road structures in reinforced concrete depends on the exposure of the elements to water in liquid form or vapour and to other aggressive agents such as chloride. Current models of ionic transport neglect the effect of real ionic concentration in contact with concrete structures, it means boundary conditions are considered with simple tendency as uniform concentration during the winter period and model parameters are derived from the fitting method. Therefore, it implies in ineffective prediction models of deterioration, i.e. steel rebar corrosion by chloride presence or carbonation, alkali-granular reaction, acid attacks, etc. Structure are sensitive to their environment and their interaction with it is directly related to the processes of deterioration. The degradation of structures exposed to salt-laden mist is faster in the wetter areas. On the contrary, the deterioration of the structures caused by salt spray in the drier zone is slower. The structures, exposed to splashing (precipitation, wind, splash, etc.), have a slower rate of degradation in the wetter regions. The amount of rain has an indirect effect in the process of deterioration of the structure exposed to salt-laden mist because it changes the contact time of chloride on the surface of the structures. For this purpose, a unique exposure monitoring was developed. This mobile station, named MExStUL, contains an atmospheric sensor and new possibilities of chloride detection contained in splashes, mist and static water near the road improving the real exposure of structure and the boundary conditions. First results highlight the real influence of environmental parameters on structures durability on highways. Salt concentration is not uniform during winter period and water thickness demonstrate important periods of drying

Cross sections relevant to gamma-ray line emission in solar flares:3^3He-induced reactions on 16^{16}O nuclei

Gamma-ray production cross sections have been measured for gamma-ray lines copiously emitted in the $^3$He bombardment of $^{16}$O nuclei: the 937, 1042 and 1081 keV lines of $^{18}$F and the 1887 keV line of $^{18}$Ne. Four Ge detectors with BGO shielding for Compton suppression were used to measure the angular distributions of the gamma-rays. The excitation functions have been obtained for $^3$He bombarding energies from 3.7 to 36 MeV. Total cross sections are tabulated for calculations relevant to gamma-ray astronomy. The importance of these lines as diagnosis for the presence and properties of accelerated $^3$He in solar flares is discussed in light of the measured cross sections.Comment: Phys. Rev. C68 (2003) 0258XX, in pres

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

Fine Definition of the CXCR4-Binding Region on the V3 Loop of Feline Immunodeficiency Virus Surface Glycoprotein

The chemokine receptor CXCR4 is shared by primary and laboratory-adapted strains of feline immunodeficiency virus (FIV) for viral entry. Our previous studies implicated a contiguous nine-amino-acid region of the V3 loop of the FIV envelope surface as important in CXCR4 binding and virus entry. The binding is specific for CXCR4 since it can be inhibited by AMD3100, a selective CXCR4 inhibitor. Additional site-directed mutagenesis was used to further reveal the key residues. Binding studies indicated that basic residues R395, K397, R399 as well as N398 are critical for CXCR4 binding. The effect of other amino acid residues on receptor binding depends on the type of amino acid residue substituted. The binding study results were confirmed on human CXCR4-expressing SupT1 cells and correlated with entry efficiency using a virus entry assay. Amino acid residues critical for CXCR4 are not critical for interactions with the primary binding receptor CD134, which has an equivalent role as CD4 for HIV-1 binding. The ELISA results show that W394 and W400 are crucial for the recognition by neutralizing anti-V3 antibodies. Since certain strains of HIV-1 also use CXCR4 as the entry receptor, the findings make the feline model attractive for development of broad-based entry antagonists and for study of the molecular mechanism of receptor/virus interactions

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

CD160-Associated CD8 T-Cell Functional Impairment Is Independent of PD-1 Expression.

Expression of co-inhibitory molecules is generally associated with T-cell dysfunction in chronic viral infections such as HIV or HCV. However, their relative contribution in the T-cell impairment remains unclear. In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160+ CD8 T cells may be independent of PD-1 expression. The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160+ CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin