Mutations within the Primer Binding Site of the Human Immunodeficiency Virus Type 1 Define Sequence Requirements Essential for Reverse Transcription

AbstractThe primer binding site (PBS) is involved in two stages during the reverse transcription of the retroviral RNA genome. In the early stage, the PBS provides complementary sequences through which tRNALys,3binds the viral RNA genome to initiate minus-strand DNA synthesis; in the later stages, complementarity between the plus- and minus-strand copies of the PBS is required to facilitate the second template transfer needed to complete reverse transcription. We previously constructed a mutant HIV-1 proviral genome, designated as pHXB2PBS(pheC + 5) (now referred to as pheC + 5), which was used to identify regions of the PBS involved in the initiation and second template transfer steps of reverse transcription. To further define the sequence requirements of the PBS for the initiation of reverse transcription, we have made single nucleotide substitutions within the first six nucleotides of the pheC + 5 PBS. Our results demonstrate that mutations within the first five nucleotides of the PBS which disrupt base paring with tRNALys,3-PBS results in an noninfectious virus; a G-U base pair at position six of the tRNALys,3-PBS complex was tolerated. In contrast to the requirements for initiation, we found that complementary binding between only three base pairs of the plus- and minus-strand PBSs was required for the extension of plus-strand DNA during the second template transfer. Furthermore, regions of the minus-strand DNA of up to 24 nucleotides could be looped-out to facilitate the complementarity required for the completion of plus-strand DNA synthesis. Taken together, the results of our studies demonstrate that different features of the PBS with respect to RNA:RNA and DNA:DNA interactions are required for initiation of reverse transcription and the completion of plus-strand DNA synthesis, respectively

Uncertainties of predictions from parton distribution functions II: the Hessian method

We develop a general method to quantify the uncertainties of parton distribution functions and their physical predictions, with emphasis on incorporating all relevant experimental constraints. The method uses the Hessian formalism to study an effective chi-squared function that quantifies the fit between theory and experiment. Key ingredients are a recently developed iterative procedure to calculate the Hessian matrix in the difficult global analysis environment, and the use of parameters defined as components along appropriately normalized eigenvectors. The result is a set of 2d Eigenvector Basis parton distributions (where d=16 is the number of parton parameters) from which the uncertainty on any physical quantity due to the uncertainty in parton distributions can be calculated. We illustrate the method by applying it to calculate uncertainties of gluon and quark distribution functions, W boson rapidity distributions, and the correlation between W and Z production cross sections.Comment: 30 pages, Latex. Reference added. Normalization of Hessian matrix changed to HEP standar

Gluon polarization in the proton

We combine heavy-quark renormalization group arguments with our understanding of the nucleon's wavefunction to deduce a bound on the gluon polarization Delta g in the proton. The bound is consistent with the values extracted from spin experiments at COMPASS and RHIC.Comment: 4 page

Healthcare Staffs’ Experiences and Perceptions of Caring for People with Dementia in the Acute Setting: Qualitative Evidence Synthesis

Background Dementia is a global issue, with increasing prevalence rates impacting on health services internationally. People with dementia are frequently admitted to hospital, an environment that may not be suited to their needs. While many initiatives have been developed to improve their care in the acute setting, there is a lack of cohesive understanding of how staff experience and perceive the care they give to people with dementia in the acute setting. Objectives The aim of this qualitative synthesis was to explore health care staffs’ experiences and perceptions of caring for people with dementia in the acute setting. Qualitative synthesis can bring together isolated findings in a meaningful way that can inform policy development. Settings A screening process, using inclusion/exclusion criteria, identified qualitative studies that focused on health care staff caring for people with dementia in acute settings. Participants Twelve reports of nine studies were included for synthesis. Data extraction was conducted on each report by two researchers. Methods Framework synthesis was employed using VIPS framework, using Values, Individualised, Perspective and Social and psychological as concepts to guide synthesis. The VIPS framework has previously been used for exploring approaches to caring for people with dementia. Quality appraisal was conducted using Critical Appraisal Skills Programme (CASP) and NVivo facilitated sensitivity analysis to ensure confidence in the findings. Results Key themes, derived from VIPS, included a number of specific subthemes that examined: infrastructure and care pathways, person-centred approaches to care, how the person interacts with their environment and other patients, and family involvement in care decisions. The synthesis identified barriers to appropriate care for the person with dementia. These include ineffective pathways of care, unsuitable environments, inadequate resources and staffing levels and lack of emphasis on education and training for staff caring for people with dementia. Conclusions This review has identified key issues in the care of people with dementia in the acute setting: improving pathways of care, creating suitable environments, addressing resources and staffing levels and placing emphasis on the education for staff caring for people with dementia. Recommendations are made for practice consideration, policy development and future research. Leadership is required to instil the values needed to care for this client group in an effective and personcentred way. Qualitative evidence synthesis can inform policy and in this case, recommends VIPS as a suitable framework for guiding decisions around care for people with dementia in acute settings

Geochemical characterization of supraglacial debris via in situ and optical remote sensing methods: a case study in Khumbu Himalaya, Nepal

Surface glacier debris samples and field spectra were collected from the ablation zones of Nepal Himalaya Ngozumpa and Khumbu glaciers in November and December 2009. Geochemical and mineral compositions of supraglacial debris were determined by X-ray diffraction and X-ray fluorescence spectroscopy. This composition data was used as ground truth in evaluating field spectra and satellite supraglacial debris composition and mapping methods. Satellite remote sensing methods for characterizing glacial surface debris include visible to thermal infrared hyper- and multispectral reflectance and emission signature identification, semi-quantitative mineral abundance indicies and spectral image composites. Satellite derived supraglacial debris mineral maps displayed the predominance of layered silicates, hydroxyl-bearing and calcite minerals on Khumbu Himalayan glaciers. Supraglacial mineral maps compared with satellite thermal data revealed correlations between glacier surface composition and glacier surface temperature. Glacier velocity displacement fields and shortwave, thermal infrared false color composites indicated the magnitude of mass flux at glacier confluences. The supraglacial debris mapping methods presented in this study can be used on a broader scale to improve, supplement and potentially reduce errors associated with glacier debris radiative property, composition, areal extent and mass flux quantifications

Electrical characterization of the soft breakdown failure mode in MgO layers

The soft breakdown (SBD) failure mode in 20 nm thick MgO dielectric layers grown on Si substrates was investigated. We show that during a constant voltage stress, charge trapping and progressive breakdown coexist, and that the degradation dynamics is captured by a power-law time dependence. We also show that the SBD current-voltage (I-V) characteristics follow the power-law model I = aVb typical of this conduction mechanism but in a wider voltage window than the one reported in the past for SiO2. The relationship between the magnitude of the current and the normalized differential conductance was analyzed