Long RNA sequencing and ribosome profiling of inflamed beta-cells reveal an extensive translatome landscape

Type 1 diabetes (T1D) is an autoimmune disease characterized by autoreactive T cell-mediated destruction of the insulin-producing pancreatic beta -cells. Increasing evidence suggest that the beta -cells themselves contribute to their own destruction by generating neoantigens through the production of aberrant or modified proteins that escape central tolerance. We recently demonstrated that ribosomal infidelity amplified by stress could lead to the generation of neoantigens in human beta -cells, emphasizing the participation of nonconventional translation events in autoimmunity, as occurring in cancer or virus-infected tissues. Using a transcriptome-wide profiling approach to map translation initiation start sites in human beta -cells under standard and inflammatory conditions, we identify a completely new set of polypeptides derived from noncanonical start sites and translation initiation within long noncoding RNA. Our data underline the extreme diversity of the beta -cell translatome and may reveal new functional biomarkers for beta -cell distress, disease prediction and progression, and therapeutic intervention in T1D.Molecular Epidemiolog

Protons in near earth orbit

The proton spectrum in the kinetic energy range 0.1 to 200 GeV was measured by the Alpha Magnetic Spectrometer (AMS) during space shuttle flight STS-91 at an altitude of 380 km. Above the geomagnetic cutoff the observed spectrum is parameterized by a power law. Below the geomagnetic cutoff a substantial second spectrum was observed concentrated at equatorial latitudes with a flux ~ 70 m^-2 sec^-1 sr^-1. Most of these second spectrum protons follow a complicated trajectory and originate from a restricted geographic region.Comment: 19 pages, Latex, 7 .eps figure

A Study of Cosmic Ray Secondaries Induced by the Mir Space Station Using AMS-01

The Alpha Magnetic Spectrometer (AMS-02) is a high energy particle physics experiment that will study cosmic rays in the $\sim 100 \mathrm{MeV}$ to $1 \mathrm{TeV}$ range and will be installed on the International Space Station (ISS) for at least 3 years. A first version of AMS-02, AMS-01, flew aboard the space shuttle \emph{Discovery} from June 2 to June 12, 1998, and collected $10^8$ cosmic ray triggers. Part of the \emph{Mir} space station was within the AMS-01 field of view during the four day \emph{Mir} docking phase of this flight. We have reconstructed an image of this part of the \emph{Mir} space station using secondary $\pi^-$ and $\mu^-$ emissions from primary cosmic rays interacting with \emph{Mir}. This is the first time this reconstruction was performed in AMS-01, and it is important for understanding potential backgrounds during the 3 year AMS-02 mission.Comment: To be submitted to NIM B Added material requested by referee. Minor stylistic and grammer change

Measurement of the Charged Multiplicities in b, c and Light Quark Events from Z0 Decays

Average charged multiplicities have been measured separately in $b$, $c$ and light quark ($u,d,s$) events from $Z^0$ decays measured in the SLD experiment. Impact parameters of charged tracks were used to select enriched samples of $b$ and light quark events, and reconstructed charmed mesons were used to select $c$ quark events. We measured the charged multiplicities: $\bar{n}_{uds} = 20.21 \pm 0.10 (\rm{stat.})\pm 0.22(\rm{syst.})$, $\bar{n}_{c} = 21.28 \pm 0.46(\rm{stat.}) ^{+0.41}_{-0.36}(\rm{syst.})$ $\bar{n}_{b} = 23.14 \pm 0.10(\rm{stat.}) ^{+0.38}_{-0.37}(\rm{syst.})$, from which we derived the differences between the total average charged multiplicities of $c$ or $b$ quark events and light quark events: $\Delta \bar{n}_c = 1.07 \pm 0.47(\rm{stat.})^{+0.36}_{-0.30}(\rm{syst.})$ and $\Delta \bar{n}_b = 2.93 \pm 0.14(\rm{stat.})^{+0.30}_{-0.29}(\rm{syst.})$. We compared these measurements with those at lower center-of-mass energies and with perturbative QCD predictions. These combined results are in agreement with the QCD expectations and disfavor the hypothesis of flavor-independent fragmentation.Comment: 19 pages LaTex, 4 EPS figures, to appear in Physics Letters

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

A SNP panel for identification of DNA and RNA specimens

Development and application of statistical models for medical scientific researc

Neuroimaging and Responsibility Assessments

Could neuroimaging evidence help us to assess the degree of a person’s responsibility for a crime which we know that they committed? This essay defends an affirmative answer to this question. A range of standard objections to this high-tech approach to assessing people’s responsibility is considered and then set aside, but I also bring to light and then reject a novel objection—an objection which is only encountered when functional (rather than structural) neuroimaging is used to assess people’s responsibility

America's Rural Hospitals: A Selective Review of 1980s Research

We review 1980s research on American rural hospitals within the context of a decade of increasing restrictiveness in the reimbursement and operating environments. Areas addressed include rural hospital definitions, organizational and financial performance, and strategic management activities. The latter category consists of hospital closure, diversification and vertical integration, swing-bed conversion, sole community provider designation, horizontal integration and multihospital system affiliation, marketing, and patient retention. The review suggests several research needs, including: developing more meaningful definitions of rural hospitals, engaging in methodologically sound work on the effects of innovative programs and strategic management activities—including conversion of the facility itself—on rural hospital performance, and completing studies of the effects of rural hospital closure or conversion on the health of the communities served.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74857/1/j.1748-0361.1990.tb00682.x.pd

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations

Cellular mechanisms in basic and clinical gastroenterology and hepatolog