Targeted Derepression of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat by Pyrrole-Imidazole Polyamides

The host factor LSF represses the human immunodeficiency virus type 1 long terminal repeat (LTR) by mediating recruitment of histone deacetylase. We show that pyrrole-imidazole polyamides targeted to the LTR can specifically block LSF binding both in vitro and within cells via direct access to chromatin, resulting in increased LTR expression

Spatial Variation in Otolith Chemistry of Atlantic Croaker Larvae in the Mid-Atlantic Bight

Larval Atlantic croaker Micropogonias undulatus (1 to 7 mm in standard length) were collected on the east coast of the United States from North Carolina to Delaware during 2000. We defined 3 water-mass boundaries for potential groups of spawning Atlantic croaker using temperature and salinity measured at each sampling station. We tested the hypothesis that distinct otolith chemistries existed among 3 groups of larval Atlantic croaker collected from these water masses using solution-based inductively coupled plasma-mass spectrometry. Multivariate analysis of variance indicated that otolith chemistry differed significantly among water masses. Using a quadratic discriminant function, we were able to correctly classify fish from the Mid-Atlantic Bight (MAB) 73 % of the time, South Atlantic Bight (SAB) 53 % of the time, and Chesapeake Bay plume 36 % of the time. The correct reclassification rates observed were significantly better than random. Results from this study indicate that it is possible to obtain measurable elemental concentrations from otoliths much smaller than previously analyzed (weight 0.015 to 1.976 μg). Moreover, contrary to previous studies, our results indicate that it is possible to distinguish natal signatures among larvae on different spawning grounds in the MAB and SAB. Further, this new information could benefit investigations of dispersal from offshore spawning grounds to estuaries or other nursery habitats

Walking a High Beam: The Balance Between Employment Stability, Workplace Flexibility, and Nonresident Father Involvement

Compared with resident fathers, nonresident fathers are more likely to be unemployed or underemployed and less likely, when they are employed, to have access to flexible work arrangements. Although lack of employment stability is associated with lower levels of father involvement, some research shows that increased stability at work without increased flexibility is negatively related to involvement. Using data from the Fragile Families and Child Wellbeing Study (N = 895), the authors examined the relationship between nonresident fathers’ employment stability, workplace flexibility, and father involvement. Results indicate that workplace flexibility, but not employment stability, is associated with higher levels of involvement. Policy and practice implications are discussed

Patterns of Larval Atlantic Croaker Ingress into Chesapeake Bay, USA

We compared ingress patterns of Atlantic croaker Micropogonias undulatus larvae into Chesapeake Bay, USA, with published ingress patterns through barrier island inlets, the accepted model for larval fish ingress. This model asserts that larvae ingress on night flood tides at the flooddominated side of the inlet and at all depths. At the Chesapeake Bay mouth and in the adjacent coastal waters, we compared the distribution of abundance, size, age, and growth rates of croaker prior to ingress, In contrast to the barrier island inlet model, croaker larvae were more abundant at depth than closer to the surface regardless of location. However, the response to light was variable, where croaker larvae farther offshore showed no response to light, but croaker larvae in the bay mouth were more abundant at night. Croaker larvae followed an expected pattern of increasing age and length from offshore stations to the bay mouth station. Further, among nearshore coastal stations there was evidence of larger and older croaker larvae at the northern portion of the bay mouth than at middle or southern stations. Patterns in growth were similar at all locations, indicating the likelihood of a single source location or similar environments among transport pathways for croaker larvae. Ingress can occur across the entire mouth of Chesapeake Bay; however, net tidal inflow may result in age and size structuring, which allows more rapid movement into the northern flood-dominated portions of the bay mouth

On Steady State Neutrino Heated Ultra-Relativistic Winds from Compact Objects

We study steady state winds from compact objects in the regime where the wind velocity at infinity is ultra-relativistic. This may have relevance to some models of Gamma-Ray-Bursts (GRB's). Particular attention is paid to the case where neutrinos provide the heating. Unless the neutrino luminosity is very large, L>10^{54} erg/s, the only allowed steady state solutions are those where energy deposition is dominated by neutrino-antineutrino annihilation at the sonic point. In this case, the matter temperature near the neutron star surface is low, less than 1MeV for typical neutrino luminosities. This is in contrast to the case for sub-relativistic winds discussed in the context of supernovae where the matter temperature near the neutron star approximates the temperature characterizing the neutrinos. We also investigate the setting of the neutron to proton ratio (n/p) in these winds and find that only for large (>10 MeV) electron neutrino or electron anti-neutrino temperatures is n/p entirely determined by neutrino capture. Otherwise, n/p retains an imprint of conditions in the neutron star

Cerebral Blood Flow and Gray Matter Volume Covariance Patterns of Cognition in Aging

Advancing age results in altered cognitive and neuroimaging-derived markers of neural integrity. Whether cognitive changes are the result of variations in brain measures remains unclear and relating the two across the lifespan poses a unique set of problems. It must be determined whether statistical associations between cognitive and brain measures truly exist and are not epiphenomenal due solely to their shared relationships with age. The purpose of this study was to determine whether cerebral blood flow (CBF) and gray matter volume (GMV) measures make unique and better predictions of cognition than age alone. Multivariate analyses identified brain-wide covariance patterns from 35 healthy young and 23 healthy older adults using MRI-derived measures of CBF and GMV related to three cognitive composite scores (i.e., memory, fluid ability, and speed/attention). These brain-cognitive relationships were consistent across the age range, and not the result of epiphenomenal associations with age and each imaging modality provided its own unique information. The CBF and GMV patterns each accounted for unique aspects of cognition and accounted for nearly all the age-related variance in the cognitive composite scores. The findings suggest that measures derived from multiple imaging modalities explain larger amounts of variance in cognition providing a more complete understanding of the aging brain

Fabrication of centimeter-scale and geometrically arbitrary vascular networks using in vitro self-assembly

One of the largest challenges facing the field of tissue engineering is the incorporation of a functional vasculature, allowing effective nourishment of graft tissue beyond diffusion length scales. Here, we demonstrate a methodology for inducing the robust self-assembly of endothelial cells into stable three-dimensional perfusable networks on millimeter and centimeter length scales. Utilizing broadly accessible cell strains and reagents, we have rigorously tested a state space of cell densities (0.5-2.0 × 106 cell/mL) and collagen gel densities (2-6 mg/mL) that result in robust vascular network formation. Further, over the range of culture conditions with which we observed robust network formation, we advanced image processing algorithms and quantitative metrics to assess network connectivity, coverage, tortuosity, lumenization, and vessel diameter. These data demonstrate that decreasing collagen density produced more connected networks with higher coverage. Finally, we demonstrated that this methodology results in the formation of perfusable networks, is extensible to arbitrary geometries and centimeter scales, and results in networks that remain stable for 21 days without the need for the co-culture of supporting cells. Given the robustness and accessibility, this system is ideal for studies of tissue-scale biology, as well as future studies on the formation and remodeling of larger engineered graft tissues

Hybrid Lattice-Boltzmann-Potential Flow Simulations of Turbulent Flow around Submerged Structures

We report on the development and validation of a 3D hybrid Lattice Boltzmann Model (LBM), with Large Eddy Simulation (LES), to simulate the interactions of incompressible turbulent flows with ocean structures. The LBM is based on a perturbation method, in which the velocity and pressure are expressed as the sum of an inviscid flow and a viscous perturbation. The far- to near-field flow is assumed to be inviscid and represented by potential flow theory, which can be efficiently modeled with a Boundary Element Method (BEM). The near-field perturbation flow around structures is modeled by the Navier–Stokes (NS) equations, based on a Lattice Boltzmann Method (LBM) with a Large Eddy Simulation (LES) of the turbulence. In the paper, we present the hybrid model formulation, in which a modified LBM collision operator is introduced to simulate the viscous perturbation flow, resulting in a novel perturbation LBM (pLBM) approach. The pLBM is then extended for the simulation of turbulence using the LES and a wall model to represent the viscous/turbulent sub-layer near solid boundaries. The hybrid model is first validated by simulating turbulent flows over a flat plate, for moderate to large Reynolds number values, Re ∈ [3.7×104;1.2×106]; the plate friction coefficient and near-field turbulence properties computed with the model are found to agree well with both experiments and direct NS simulations. We then simulate the flow past a NACA-0012 foil using a regular LBM-LES and the new hybrid pLBM-LES models with the wall model, for Re = 1.44 x 106. A good agreement is found for the computed lift and drag forces, and pressure distribution on the foil, with experiments and results of other numerical methods. Results obtained with the pLBM model are either nearly identical or slightly improved, relative to those of the standard LBM, but are obtained in a significantly smaller computational domain and hence at a much reduced computational cost, thus demonstrating the benefits of the new hybrid approach

Does malaria cause diarrhoea? A systematic review

Malaria is a systemic febrile disease that may progress to prostration, respiratory distress, encephalopathy, anemia, and death. Malaria is also an established risk factor for invasive bacterial disease caused, in the majority of cases, by invasive enteropathogens and in particular by non-Typhoidal Salmonella (NTS). Whilst various malaria-related pathologies have been implicated in the risk of NTS bacteraemia in animal models, including intestinal dysbiosis and loss of gut homeostasis, clinical evidence is lacking. As a first step in gathering such evidence, we conducted a systematic review of clinical and epidemiological studies reporting the prevalence of diarrhoea among malaria cases and vice versa. Database searches for "plasmodium" and "diarrhoea" identified 1,771 articles; a search for "plasmodium" and "gastroenteritis" identified a further 215 articles. After review, 66 articles specified an association between the search terms and referred primarily, but not exclusively, to Plasmodium falciparum infections. Overall, between 1.6 and 44% of patients with acute malaria infection reported symptoms of diarrhoea (812 of 7,267 individuals, 11%) whereas 5-42% of patients presenting to hospital with diarrhoea had an underlying malaria parasite infection (totaling 749 of 2,937 individuals, 26%). However, given the broad range of estimates, a paucity of purposeful case control or longitudinal studies, and varied or poorly specified definitions of diarrhoea, the literature provides limited evidence to draw any firm conclusions. The relationship between malaria and gastrointestinal disturbance thus remains unclear. Carefully designed case-control studies and prospective longitudinal studies are required to confidently assess the prevalence and significance of intestinal manifestations of malaria parasite infection