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

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Dinosaur tracks from the Kilmaluag Formation (Bathonian, Middle Jurassic) of Score Bay, Isle of Skye, Scotland, UK

Tracks of a juvenile theropod dinosaur with footprint lengths of between 2 and 9 cm as well as adults of the same ichnospecies with footprints of about 15–25 cm in length were found in the Bathonian (Middle Jurassic) Kilmaluag Formation of Score Bay, northwestern Trotternish Peninsula, Isle of Skye, Scotland, UK. Two footprint sizes occur together on the same bedding plane in the central portion of Score Bay, both in situ and on loose blocks. Another horizon containing footprints above this was also identified. The footprints from the lowest horizon were produced in a desiccated silty mud that was covered with sand. A close association of both adults and juveniles with similar travel direction indicated by the footprints may suggest post-hatching care in theropod dinosaurs. Other footprints, produced on a rippled sandy substrate, have been found on the slightly higher bedding plane at this locality. Loose blocks found 130 m to the northeast in the central part of Score Bay have not been correlated with any in situ sediments, but were preserved in a similar manner to those from the higher bedding plane. These tracks represent the youngest dinosaur remains yet found in Scotland

Space-time smoothing of complex survey data: Small area estimation for child mortality

Many people living in low- and middle-income countries are not covered by civil registration and vital statistics systems. Consequently, a wide variety of other types of data, including many household sample surveys, are used to estimate health and population indicators. In this paper we combine data from sample surveys and demographic surveillance systems to produce small area estimates of child mortality through time. Small area estimates are necessary to understand geographical heterogeneity in health indicators when full-coverage vital statistics are not available. For this endeavor spatio-temporal smoothing is beneficial to alleviate problems of data sparsity. The use of conventional hierarchical models requires careful thought since the survey weights may need to be considered to alleviate bias due to nonrandom sampling and nonresponse. The application that motivated this work is an estimation of child mortality rates in five-year time intervals in regions of Tanzania. Data come from Demographic and Health Surveys conducted over the period 1991-2010 and two demographic surveillance system sites. We derive a variance estimator of under five years child mortality that accounts for the complex survey weighting. For our application, the hierarchical models we consider include random effects for area, time and survey and we compare models using a variety of measures including the conditional predictive ordinate (CPO). The method we propose is implemented via the fast and accurate integrated nested Laplace approximation (INLA).Comment: Published at http://dx.doi.org/10.1214/15-AOAS872 in the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Primary and secondary controls on reservoir quality: relationships between lithofacies and the development of deformation bands

Primary sedimentological processes in mixed eolian-fluvial systems can result in lithological variability at the sub-seismic scale. This variation in genetic origin has a direct control on the porosity and permeability of a body of sediment, with variations in lithofacies types, their assemblages and contacts responsible for creating fluid pathways or baffles. Post-depositional near-surface and deep process diagenesis affects original porosity and permeabilities through mineral dissolution and re-precipitation, and the generation of stress induced fractures. Examination of bedrock exposure and drillcore from the depositionally heterogeneous Triassic Sherwood Sandstone of north-west England demonstrates that there is a strong facies control on the presence and type of secondary processes, namely in the form of deformation bands. This is despite the entire range of lithofacies being subject to the same regional and local stresses. The mixed eolian-fluvial Sherwood Sandstone Group exhibits a wide range of facies types which allows a good insight in to those most susceptible to deformation band formation. Preliminary work indicates that the eolian grainfall and grainflow facies types are at most risk of being host to deformation bands above all other facies types (both eolian and fluvial). This is significant as both of these facies have very good permeabilities in excess of 6000 mD (millidarcy), whilst the deformation bands have significantly less ranging from 0.1-10 mD. The deformation bands are also identified to occur in a range of styles that vary from: i) isolated thin (1-2 mm thick) individual seams, ii) complex conjugate interlocking sets, and iii) chaotic thick amalgamations of multiple deformation bands ranging from 5-120 cm thick. Each of the deformation types has been constrained in three dimensions and a range of idealised conceptual models are presented that indicate the potential of effects on reservoir quality

Inferior vena cava branch variations in C57BL/6 mice have an impact on thrombus size in an IVC ligation (stasis) model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110835/1/jth12866.pd

Single capstone or multiple cornerstones? Distributed model of capstone subjects in construction education

Capstone experiences provide critical opportunities for undergraduate students to integrate and apply the skills and knowledge they have previously developed in their degree or program. Commonly, this involves students engaging in learning experiences that involve real-world issues and which in turn enhance the student experience and employability skills. The research on capstone experiences in the construction management education literature indicates a need to develop customized delivery models that addresses the specific requirements of construction industry and education providers. This paper aims to showcase an innovative model of distributed delivery for multiple capstones (cornerstones) in a construction management program. The case study described in this paper realized an improvement in capstone design and practice-based learning by incrementally enhancing a student's knowledge of construction project management skills. The model of multiple capstones discussed here is applicable to diverse disciplines, including construction engineering and management programs

Wind field and sex constrain the flight speeds of central-place foraging albatrosses

By extracting energy from the highly dynamic wind and wave fields that typify pelagic habitats, albatrosses are able to proceed almost exclusively by gliding flight. Although energetic costs of gliding are low, enabling breeding albatrosses to forage hundreds to thousands of kilometers from their colonies, these and time costs vary with relative wind direction. This causes albatrosses in some areas to route provisioning trips to avoid headwind flight, potentially limiting habitat accessibility during the breeding season. In addition, because female albatrosses have lower wing loadings than males, it has been argued that they are better adapted to flight in light winds, leading to sexual segregation of foraging areas. We used satellite telemetry and immersion logger data to quantify the effects of relative wind speed, sex, breeding stage, and trip stage on the ground speeds (Vg) of four species of Southern Ocean albatrosses breeding at South Georgia. Vg was linearly related to the wind speed component in the direction of flight (Vwf), its effect being greatest on Wandering Albatrosses Diomedea exulans, followed by Black-browed Albatrosses Thalassarche melanophrys, Light-mantled Sooty Albatrosses Phoebatria palpebrata, and Gray-headed Albatrosses T. chrysostoma. Ground speeds at Vwf = 0 were similar to airspeeds predicted by aerodynamic theory and were higher in males than in females. However, we found no evidence that this led to sexual segregation, as males and females experienced comparable wind speeds during foraging trips. Black-browed, Gray-headed, and Light-mantled Sooty Albatrosses did not engage in direct, uninterrupted bouts of flight on moonless nights, but Wandering Albatrosses attained comparable Vg night and day, regardless of lunar phase. Relative flight direction was more important in determining Vg than absolute wind speed. When birds were less constrained in the middle stage of foraging trips, all species flew predominantly across the wind. However, in some instances, commuting birds encountered headwinds during outward trips and tail winds on their return, with the result that Vg was 1.0–3.4 m/s faster during return trips. This, we hypothesize, could result from constraints imposed by the location of prey resources relative to the colony at South Georgia or could represent an energy optimization strategy

Debating DSM-5:diagnosis and the sociology of critique

The development of the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders—the DSM-5—has reenergised and driven further forward critical discourse about the place and role of diagnosis in mental health. The DSM-5 has attracted considerable criticism, not least about its role in processes of medicalisation. This paper suggests the need for a sociology of psychiatric critique. Sociological analysis can help map fields of contention, and cast fresh light on the assumptions and nuances of debate around the DSM-5; it underscores the importance of diagnosis to the governance of social and clinical life, as well as the wider discourses critical commentaries connect with and are activated by. More normatively, a sociology of critique can indicate which interests and values are structuring the dialogues being articulated, and just how diverse clinical opinion regarding the DSM can actually be. This has implications for the considerations of health services and policy decision-makers who might look to such debates for guidance