Studies on Monitoring and Tracking Genetic Resources: An Executive Summary

The principles underlying fair and equitable sharing of benefits derived from the utilization of genetic resources are set out in Article 15 of the UN Convention on Biological Diversity, which stipulate that access to genetic resources is subject to the prior informed consent of the country where such resources are located and to mutually agreed terms regarding the sharing of benefits that could be derived from such access. One issue of particular concern for provider countries is how to monitor and track genetic resources once they have left the provider country and enter into use in a variety of forms. This report was commissioned to provide a detailed review of advances in DNA sequencing technologies, as those methods apply to identification of genetic resources, and the use of globally unique persistent identifiers for persistently linking to data and other forms of digital documentation that is linked to individual genetic resources. While the report was written for an audience with a mixture of technical, legal, and policy backgrounds it is relevant to the genomics community as it is an example of downstream application of genomics information

TGF-β and IL-10 Production by HIV-Specific CD8+ T Cells Is Regulated by CTLA-4 Signaling on CD4+ T Cells

Immune dysregulation in HIV-1 infection is associated with increased expression of inhibitory molecules such as CTLA-4, TGF-β, and IL-10. In this study we examined one potential mechanism for regulating TGF-β and IL-10 expression by HIV-specific suppressor CD8+ T cells. No overlap between TGF-β, IL-10, and IFN-γ cytokine production by HIV-specific CD8+ T cells was observed. TGF-β positive and IL-10 positive cells were FOXP3 negative, CD25 negative, and displayed a heterogeneous surface expression of CD127. TGF-β and IL-10 positive CD8+ T cells did not express CTLA-4. Nevertheless, CTLA-4 blockade resulted in a significant decrease in HIV-specific TGF-β positive and IL-10 positive CD8+ T cell responses, and a concomitant increase in HIV-specific IFN-γ positive CD8+ T cell responses. Depletion of CD4+ T cells abrogated the impact of CTLA-4 on HIV-specific TGF-β positive and IL-10 positive CD8+ T cells. Our study suggests that CTLA-4 Signaling on CD4+ T cells regulates the inhibitory functions of the HIV-specific suppressor CD8+ T cells

Structure of a Protozoan Virus from the Human Genitourinary Parasite Trichomonas vaginalis

The flagellated protozoan Trichomonas vaginalis is an obligate human genitourinary parasite and the most frequent cause of sexually transmitted disease worldwide. Most clinical isolates of T. vaginalis are persistently infected with one or more double-stranded RNA (dsRNA) viruses from the genus Trichomonasvirus, family Totiviridae, which appear to influence not only protozoan biology but also human disease. Here we describe the three-dimensional structure of Trichomonas vaginalis virus 1 (TVV1) virions, as determined by electron cryomicroscopy and icosahedral image reconstruction. The structure reveals a T = 1 capsid comprising 120 subunits, 60 in each of two nonequivalent positions, designated A and B, as previously observed for fungal Totiviridae family members. The putative protomer is identified as an asymmetric AB dimer consistent with either decamer or tetramer assembly intermediates. The capsid surface is notable for raised plateaus around the icosahedral 5-fold axes, with canyons connecting the 2- and 3-fold axes. Capsid-spanning channels at the 5-fold axes are unusually wide and may facilitate release of the viral genome, promoting dsRNA-dependent immunoinflammatory responses, as recently shown upon the exposure of human cervicovaginal epithelial cells to either TVV-infected T. vaginalis or purified TVV1 virions. Despite extensive sequence divergence, conservative features of the capsid reveal a helix-rich fold probably derived from an ancestor shared with fungal Totiviridae family members. Also notable are mass spectrometry results assessing the virion proteins as a complement to structure determination, which suggest that translation of the TVV1 RNA-dependent RNA polymerase in fusion with its capsid protein involves −2, and not +1, ribosomal frameshifting, an uncommonly found mechanism to date

Disparities in registration and use of an online patient portal among older adults: findings from the LitCog cohort

(C) The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved.Financial disclosure: This project was supported by the National Institute on Aging (R01 AG030611), the National Center for Research Resources (5UL1RR025741), and the National Center for Advancing Translational Sciences (Grant 8UL1TR000150). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Smith is currently supported by a Cancer Research UK Fellowship

Measurement of Charged Pion Production Yields off the NuMI Target

The fixed-target MIPP experiment, Fermilab E907, was designed to measure the production of hadrons from the collisions of hadrons of momenta ranging from 5 to 120 GeV/c on a variety of nuclei. These data will generally improve the simulation of particle detectors and predictions of particle beam fluxes at accelerators. The spectrometer momentum resolution is between 3 and 4%, and particle identification is performed for particles ranging between 0.3 and 80 GeV/c using $dE/dx$, time-of-flight and Cherenkov radiation measurements. MIPP collected $1.42 \times10^6$ events of 120 GeV Main Injector protons striking a target used in the NuMI facility at Fermilab. The data have been analyzed and we present here charged pion yields per proton-on-target determined in bins of longitudinal and transverse momentum between 0.5 and 80 GeV/c, with combined statistical and systematic relative uncertainties between 5 and 10%.Comment: 15 pages, 13 figure

Molecular Gas in Spiral Galaxies

In this review, I highlight a number of recent surveys of molecular gas in nearby spiral galaxies. Through such surveys, more complete observations of the distribution and kinematics of molecular gas have become available for galaxies with a wider range of properties (e.g., brightness, Hubble type, strength of spiral or bar structure). These studies show the promise of both interferometers and single-dish telescopes in advancing our general understanding of molecular gas in spiral galaxies. In particular, I highlight the contributions of the recent BIMA Survey of Nearby Galaxies (SONG).Comment: 8 pages, 1 figure. To appear in the proceedings of the 4th Cologne-Bonn-Zermatt-Symposium, "The Dense Interstellar Medium in Galaxies", which was held in Zermatt, Switzerland in September 200

Forward Neutron Production at the Fermilab Main Injector

We have measured cross sections for forward neutron production from a variety of targets using proton beams from the Fermilab Main Injector. Measurements were performed for proton beam momenta of 58 GeV/c, 84 GeV/c, and 120 GeV/c. The cross section dependence on the atomic weight (A) of the targets was found to vary as $A^(alpha)$ where $\alpha$ is $0.46\pm0.06$ for a beam momentum of 58 GeV/c and 0.54$\pm$0.05 for 120 GeV/c. The cross sections show reasonable agreement with FLUKA and DPMJET Monte Carlos. Comparisons have also been made with the LAQGSM Monte Carlo.Comment: Accepted for publication in Physical Review D. This version incorporates small changes suggested by referee and small corrections in the neutron production cross sections predicted by FLUK

Understanding the impact of complicated grief on combat related posttraumatic stress disorder, guilt, suicide, and functional impairment in a clinical trial of post‐9/11 service members and veterans

BackgroundComplicated grief (CG) is a bereavement‐specific syndrome distinct from but commonly comorbid with posttraumatic stress disorder (PTSD). While bereavement is common among military personnel (Simon et al., 2018), there is little research on the impact of CG comorbidity on PTSD treatment outcomes.MethodsTo evaluate the impact of comorbid CG on PTSD treatment outcomes we analyzed data from a randomized trial comparing prolonged exposure, sertraline, and their combination in veterans with a primary diagnosis of combat‐related PTSD (n = 194). Assessment of PTSD, trauma‐related guilt, functional impairment, and suicidal ideation and behavior occurred at baseline and weeks 6, 12, and 24 during the 24‐week trial.ResultsCG was associated with lower PTSD treatment response (odds ratio (OR) = 0.29, 95% confidence interval (CI) [0.12, 0.69], p = 0.005) and remission (OR = 0.28, 95% CI [0.11, 0.71], p = 0.007). Those with CG had greater severity of PTSD (p = 0.005) and trauma‐related guilt (<0.001) at baseline and endpoint. In addition, those with CG were more likely to experience suicidal ideation during the study (CG: 35%, 14/40 vs. no CG 15%, 20/130; OR = 3.01, 95% CI [1.29, 7.02], p = 0.011).ConclusionsComorbid CG is associated with elevated PTSD severity and independently associated with poorer endpoint treatment outcomes in veterans with combat‐related PTSD, suggesting that screening and additional intervention for CG may be needed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153078/1/da22911_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153078/2/da22911.pd

Numerical Relativity: A review

Computer simulations are enabling researchers to investigate systems which are extremely difficult to handle analytically. In the particular case of General Relativity, numerical models have proved extremely valuable for investigations of strong field scenarios and been crucial to reveal unexpected phenomena. Considerable efforts are being spent to simulate astrophysically relevant simulations, understand different aspects of the theory and even provide insights in the search for a quantum theory of gravity. In the present article I review the present status of the field of Numerical Relativity, describe the techniques most commonly used and discuss open problems and (some) future prospects.Comment: 2 References added; 1 corrected. 67 pages. To appear in Classical and Quantum Gravity. (uses iopart.cls

Repeated ovarian stimulation with corifollitropin alfa in patients in a GnRH antagonist protocol: no concern for immunogenicity

BACKGROUND One injection of corifollitropin alfa replaces the first seven daily FSH injections in controlled ovarian stimulation (COS) cycles. Repeated treatment with therapeutic proteins may cause immune responses or hypersensitivity reactions. We assessed the immunogenicity and safety of corifollitropin alfa treatment in up to three COS cycles. METHODS In this multicentre, phase III uncontrolled trial, patients (>60 kg) started treatment with one injection of 150 µg corifollitropin alfa on cycle Day 2 or 3 of menses and 0.25 mg ganielix on stimulation Day 5 or 6. Primary outcome measures were antibody formation against corifollitropin alfa (using highly sensitive radioimmunoprecipitation assay), hypersensitivity reactions, local tolerance and adverse events (AEs). RESULTS First, second and third COS cycles were started by 682, 375 and 198 patients, respectively. No clinically relevant immunogenicity or drug-related hypersensitivity was observed. For 192 patients undergoing their third cycle a post-treatment blood sample was negative in the anti-corifollitropin antibody assay, resulting in an upper limit of the one-sided 95% confidence interval (CI) of 1.5%. Most frequent AEs were procedural pain (17.7%, 95% CI: 14.9–20.8%), headache (9.1%, 95% CI: 7.0–11.5%) and pelvic pain (7.6%, 95% CI: 5.7–9.9%). Cumulative ongoing pregnancy rate after three cycles, including frozen-thawed embryo transfer cycles and spontaneous pregnancies, was 61% (95% CI: 56–65%) after censoring for patients who discontinued. CONCLUSIONS Treatment with corifollitropin alfa can safely and effectively initiate and sustain ovarian stimulation during the first 7 days of COS in normal responder patients undergoing up to three treatment cycles, without concerns of immunogenicity.Robert J. Norman, Fernando Zegers-Hochschild, Bruno S. Salle, Jolanda Elbers, Esther Heijnen, Maya Marintcheva-Petrova, and Bernadette Mannaerts for the Trust Investigator