2,537 research outputs found

    Earth-based lunar atmosphere investigation Final report

    Get PDF
    Instrumentation and results of earth-based spectrometric identification of lunar atmospheric constituents in visible regio

    Molecular motion in cell membranes: analytic study of fence-hindered random walks

    Full text link
    A theoretical calculation is presented to describe the confined motion of transmembrane molecules in cell membranes. The study is analytic, based on Master equations for the probability of the molecules moving as random walkers, and leads to explicit usable solutions including expressions for the molecular mean square displacement and effective diffusion constants. One outcome is a detailed understanding of the dependence of the time variation of the mean square displacement on the initial placement of the molecule within the confined region. How to use the calculations is illustrated by extracting (confinement) compartment sizes from experimentally reported published observations from single particle tracking experiments on the diffusion of gold-tagged G-protein coupled mu-opioid receptors in the normal rat kidney cell membrane, and by further comparing the analytical results to observations on the diffusion of phospholipids, also in normal rat kidney cells.Comment: 10 pages, 5 figure

    Key determinants of target DNA recognition by retroviral intasomes

    Get PDF
    BACKGROUND: Retroviral integration favors weakly conserved palindrome sequences at the sites of viral DNA joining and generates a short (4–6 bp) duplication of host DNA flanking the provirus. We previously determined two key parameters that underlie the target DNA preference for prototype foamy virus (PFV) and human immunodeficiency virus type 1 (HIV-1) integration: flexible pyrimidine (Y)/purine (R) dinucleotide steps at the centers of the integration sites, and base contacts with specific integrase residues, such as Ala188 in PFV integrase and Ser119 in HIV-1 integrase. Here we examined the dinucleotide preference profiles of a range of retroviruses and correlated these findings with respect to length of target site duplication (TSD). RESULTS: Integration datasets covering six viral genera and the three lengths of TSD were accessed from the literature or generated in this work. All viruses exhibited significant enrichments of flexible YR and/or selection against rigid RY dinucleotide steps at the centers of integration sites, and the magnitude of this enrichment inversely correlated with TSD length. The DNA sequence environments of in vivo-generated HIV-1 and PFV sites were consistent with integration into nucleosomes, however, the local sequence preferences were largely independent of target DNA chromatinization. Integration sites derived from cells infected with the gammaretrovirus reticuloendotheliosis virus strain A (Rev-A), which yields a 5 bp TSD, revealed the targeting of global chromatin features most similar to those of Moloney murine leukemia virus, which yields a 4 bp duplication. In vitro assays revealed that Rev-A integrase interacts with and is catalytically stimulated by cellular bromodomain containing 4 protein. CONCLUSIONS: Retroviral integrases have likely evolved to bend target DNA to fit scissile phosphodiester bonds into two active sites for integration, and viruses that cut target DNA with a 6 bp stagger may not need to bend DNA as sharply as viruses that cleave with 4 bp or 5 bp staggers. For PFV and HIV-1, the selection of signature bases and central flexibility at sites of integration is largely independent of chromatin structure. Furthermore, global Rev-A integration is likely directed to chromatin features by bromodomain and extraterminal domain proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-015-0167-3) contains supplementary material, which is available to authorized users

    Dental-related Emergency Department Visits and Community Dental Care Resources for Emergency Room Patients

    Get PDF
    BACKGROUND: The number and cost of dental-related visits to Emergency Departments (ED) is a significant issue nationwide. A better understanding of the treatment provided to ED patients presenting with dental complaints and community dental resources is needed. METHODS: A three-tiered approach included: 1) a 12-month retrospective chart review for dental-related ICD-9 visit codes at an urban academic ED in Kansas City; 2) surveys of 30 providers at the same ED regarding the dental patient process and treatment; and 3) telephone surveys of 16 Kansas City area safety net clinics regarding service access. RESULTS: Out of 49,276 ED visits, 676 were related to dental conditions (70 were repeat dental ED visits). Most patients were female (54%), white (45%), age 20-39 (65%), and self-pay (56%). The most prevalent codes utilized were dental disorder not otherwise specified (NOS; 57%), periapical abscess (22%), and dental caries NOS (15%). Nearly all providers (97%) felt comfortable seeing patients with dental complaints. Chart review indicated that patients received a dental screen/exam during 80% of the encounters, with medication provided to 90% of the patients. Over two-thirds of the providers (N = 23/30) regularly prescribed antibiotics and pain medications for their ED dental patients. ED providers performed dental procedures in 63% of the patient cases. The most common procedures included dental blocks (N = 16 providers) and incision and drainage (N = 4 providers). Only two of the 16 safety net clinics provided comprehensive dental care, almost all (94%) clinics required patients to call to schedule an appointment, and there was a two to six month waiting period for 31% of the clinics. CONCLUSION: The limited scope of dental treatment in the ED, coupled with poor availability of safety-net dental resources, may result in dental exacerbations and suboptimal patient clinical outcomes. The enhancement of safety-net dental service accessibility is crucial to reducing dental ED visits and improving dental health, particularly among low-income, self-pay populations

    Galactic Gamma-Ray Background Radiation from Supernova Remnants

    Get PDF
    The contribution of the Source Cosmic Rays (SCRs), confined in Supernova Remnants, to the diffuse high energy \gr emission above 1 GeV from the Galactic disk is studied. \grs produced by the SCRs have a much harder spectrum compared with those generated by the Galactic Cosmic Rays which occupy a much larger residence volume uniformly. SCRs contribute less than 10% at GeV energies and become dominant at \gr energies above 100 GeV. The contributions from π0\pi^0-decay and Inverse Compton \grs have comparable magnitude and spectral shape, whereas the Bremsstrahlung component is negligible. At TeV energies the contribution from SCRs increases the expected diffuse \gr flux almost by an order of magnitude. It is shown that for the inner Galaxy the discrepancy between the observed diffuse intensity and previous model predictions at energies above a few GeV can be attributed to the SCR contribution.Comment: 25 pages, 1 figures, to appear in Ap

    Mammography screening: views from women and primary care physicians in Crete

    Get PDF
    Background: Breast cancer is the most commonly diagnosed cancer among women and a leading cause of death from cancer in women in Europe. Although breast cancer incidence is on the rise worldwide, breast cancer mortality over the past 25 years has been stable or decreasing in some countries and a fall in breast cancer mortality rates in most European countries in the 1990s was reported by several studies, in contrast, in Greece have not reported these favourable trends. In Greece, the age-standardised incidence and mortality rate for breast cancer per 100.000 in 2006 was 81,8 and 21,7 and although it is lower than most other countries in Europe, the fall in breast cancer mortality that observed has not been as great as in other European countries. There is no national strategy for screening in this country. This study reports on the use of mammography among middleaged women in rural Crete and investigates barriers to mammography screening encountered by women and their primary care physicians. Methods: Design: Semi-structured individual interviews. Setting and participants: Thirty women between 45–65 years of age, with a mean age of 54,6 years, and standard deviation 6,8 from rural areas of Crete and 28 qualified primary care physicians, with a mean age of 44,7 years and standard deviation 7,0 serving this rural population. Main outcome measure: Qualitative thematic analysis. Results: Most women identified several reasons for not using mammography. These included poor knowledge of the benefits and indications for mammography screening, fear of pain during the procedure, fear of a serious diagnosis, embarrassment, stress while anticipating the results, cost and lack of physician recommendation. Physicians identified difficulties in scheduling an appointment as one reason women did not use mammography and both women and physicians identified distance from the screening site, transportation problems and the absence of symptoms as reasons for non-use. Conclusion: Women are inhibited from participating in mammography screening in rural Crete. The provision of more accessible screening services may improve this. However physician recommendation is important in overcoming women's inhibitions. Primary care physicians serving rural areas need to be aware of barriers preventing women from attending mammography screening and provide women with information and advice in a sensitive way so women can make informed decisions regarding breast caner screening

    Deciphering the folding kinetics of transmembrane helical proteins

    Full text link
    Nearly a quarter of genomic sequences and almost half of all receptors that are likely to be targets for drug design are integral membrane proteins. Understanding the detailed mechanisms of the folding of membrane proteins is a largely unsolved, key problem in structural biology. Here, we introduce a general model and use computer simulations to study the equilibrium properties and the folding kinetics of a CαC_{\alpha}-based two helix bundle fragment (comprised of 66 amino-acids) of Bacteriorhodopsin. Various intermediates are identified and their free energy are calculated toghether with the free energy barrier between them. In 40% of folding trajectories, the folding rate is considerably increased by the presence of non-obligatory intermediates acting as traps. In all cases, a substantial portion of the helices is rapidly formed. This initial stage is followed by a long period of consolidation of the helices accompanied by their correct packing within the membrane. Our results provide the framework for understanding the variety of folding pathways of helical transmembrane proteins

    Pion-Lambda-Sigma Coupling Extracted from Hyperonic Atoms

    Full text link
    The latest measurements of the atomic level width in Sigma-hyperonic Pb atom offer the most accurate datum in the region of low-energy Sigma-hyperon physics. Atomic widths are due to the conversion of Sigma-nucleon into Lambda-nucleon. In high angular momentum states this conversion is dominated by the one-pion exchange. A joint analysis of the data of the scattering of negative-Sigma on proton converting into a Lambda and a neutron and of the atomic widths allows to extract a pseudovector pion-hyperon-Sigma coupling constant of 0.048 with a statistical error of +-0.005 and a systematic one of +-0.004. This corresponds to a pseudoscalar coupling constant of 13.3 with a statistical uncertainty of 1.4 and a systematic one of 1.1.Comment: 12 pages, 1 figure, Use of Revtex.st

    A supramolecular assembly mediates lentiviral DNA integration

    Get PDF
    Retroviral integrase (IN) functions within the intasome nucleoprotein complex to catalyze insertion of viral DNA into cellular chromatin. Using cryo–electron microscopy, we now visualize the functional maedi-visna lentivirus intasome at 4.9 angstrom resolution. The intasome comprises a homo-hexadecamer of IN with a tetramer-of-tetramers architecture featuring eight structurally distinct types of IN protomers supporting two catalytically competent subunits. The conserved intasomal core, previously observed in simpler retroviral systems, is formed between two IN tetramers, with a pair of C-terminal domains from flanking tetramers completing the synaptic interface. Our results explain how HIV-1 IN, which self-associates into higher-order multimers, can form a functional intasome, reconcile the bulk of early HIV-1 IN biochemical and structural data, and provide a lentiviral platform for design of HIV-1 IN inhibitors

    Arrgh! Hollywood Targets Internet Piracy

    Get PDF
    As technology advances, the threat of rampant and unprecedented theft of digital media continues to grow. The music industry has already faced, and continues to face, this threat, but has largely failed in defending musicians’ intellectual property
    corecore