Tracking environmental trends in the Great Bay Estuarine System through comparisons of historical and present-day green and red algal community structure and nutrient content

Monitoring macroalgae populations is an effective means of detecting long term water quality changes in estuarine systems. To investigate the environmental status of New Hampshire’s Great Bay National Estuarine Research Reserve, this study assessed the abundance/distribution of macrophytes, particularly Gracilaria and Ulva species, relative to eutrophication patterns; compared historical (1970s-1990s) and current algal biomass/cover at several sites; and compared Ulva and Gracilaria tissue N/P content to ambient and historical levels. Ulva and Gracilaria biomass/cover have increased significantly at several sites. Cover by Ulva species, at seasonal maxima, was over 90 times the value recorded in the 1970s at Lubberland Creek, and exceeded 50% at all sites in the upper estuary. Gracilaria cover was greater than 25% at Depot Road in the upper estuary, whereas the historical measure was 1%. Sequencing of ITS2, rbcL and CO1 revealed the presence of previously undetected Ulva and Gracilaria species, including Gracilaria vermiculophylla (Ohmi) Papenfuss, an invasive species of Asian origin. Gracilaria vermiculophylla has exceeded G. tikvahiae as the dominant Gracilaria species in Great Bay. Historical voucher specimen screening suggests G. vermiculophylla was introduced as recently as 2003. Nitrogen and phosphorus levels are elevated in the estuary. We should expect continued seasonal nuisance algal blooms

Polarization restricts hepatitis C virus entry into HepG2 hepatoma cells

The primary reservoir for hepatitis C virus (HCV) replication is believed to be hepatocytes, which are highly polarized with tight junctions (TJ) separating their basolateral and apical domains. HepG2 cells develop polarity over time, resulting in the formation and remodeling of bile canalicular (BC) structures. HepG2 cells expressing CD81 provide a model system to study the effects of hepatic polarity on HCV infection. We found an inverse association between HepG2-CD81 polarization and HCV pseudoparticle entry. As HepG2 cells polarize, discrete pools of claudin-1 (CLDN1) at the TJ and basal/lateral membranes develop, consistent with the pattern of receptor staining observed in liver tissue. The TJ and nonjunctional pools of CLDN1 show an altered association with CD81 and localization in response to the PKA antagonist Rp-8-Br-cyclic AMPs (cAMPs). Rp-8-Br-cAMPs reduced CLDN1 expression at the basal membrane and inhibited HCV infection, supporting a model where the nonjunctional pools of CLDN1 have a role in HCV entry. Treatment of HepG2 cells with proinflammatory cytokines, tumor necrosis factor alpha and gamma interferon, perturbed TJ integrity but had minimal effect(s) on cellular polarity and HCV infection, suggesting that TJ integrity does not limit HCV entry into polarized HepG2 cells. In contrast, activation of PKC with phorbol ester reduced TJ integrity, ablated HepG2 polarity, and stimulated HCV entry. Overall, these data show that complex hepatocyte-like polarity alters CLDN1 localization and limits HCV entry, suggesting that agents which disrupt hepatocyte polarity may promote HCV infection and transmission within the liver

Pkd1 transgenic mice: Adult model of polycystic kidney disease with extrarenal and renal phenotypes

While high levels of Pkd1 expression are detected in tissues of patients with autosomal dominant polycystic kidney disease (ADPKD), it is unclear whether enhanced expression could be a pathogenetic mechanism for this systemic disorder. Three transgenic mouse lines were generated from a Pkd1-BAC modified by introducing a silent tag via homologous recombination to target a sustained wild type genomic Pkd1 expression within the native tissue and temporal regulation. These mice specifically overexpressed the Pkd1 transgene in extrarenal and renal tissues from approximately 2- to 15-fold over Pkd1 endogenous levels in a copy-dependent manner. All transgenic mice reproducibly developed tubular and glomerular cysts leading to renal insufficiency. Interestingly, Pkd1(TAG) mice also exhibited renal fibrosis and calcium deposits in papilla reminiscent of nephrolithiasis as frequently observed in ADPKD. Similar to human ADPKD, these mice consistently displayed hepatic fibrosis and approximately 15% intrahepatic cysts of the bile ducts affecting females preferentially. Moreover, a significant proportion of mice developed cardiac anomalies with severe left ventricular hypertrophy, marked aortic arch distention and/or valvular stenosis and calcification that had profound functional impact. Of significance, Pkd1(TAG) mice displayed occasional cerebral lesions with evidence of ruptured and unruptured cerebral aneurysms. This Pkd1(TAG) mouse model demonstrates that overexpression of wildtype Pkd1 can trigger the typical adult renal and extrarenal phenotypes resembling human ADPKD.This work was supported by the Canadian Institutes of Health Research (CIHR) [MOP-81325 to MT] and a CIHR Frederick Banting and Charles Best studentship to AK and a Fonds de la Recherche en Santé du Québec (FRSQ) studentship to MC

Intraoperative electrocochleographic characteristics of auditory neuropathy spectrum disorder in cochlear implant subjects

Auditory neuropathy spectrum disorder (ANSD) is characterized by an apparent discrepancy between measures of cochlear and neural function based on auditory brainstem response (ABR) testing. Clinical indicators of ANSD are a present cochlear microphonic (CM) with small or absent wave V. Many identified ANSD patients have speech impairment severe enough that cochlear implantation (CI) is indicated. To better understand the cochleae identified with ANSD that lead to a CI, we performed intraoperative round window electrocochleography (ECochG) to tone bursts in children (n = 167) and adults (n = 163). Magnitudes of the responses to tones of different frequencies were summed to measure the “total response” (ECochG-TR), a metric often dominated by hair cell activity, and auditory nerve activity was estimated visually from the compound action potential (CAP) and auditory nerve neurophonic (ANN) as a ranked “Nerve Score”. Subjects identified as ANSD (45 ears in children, 3 in adults) had higher values of ECochG-TR than adult and pediatric subjects also receiving CIs not identified as ANSD. However, nerve scores of the ANSD group were similar to the other cohorts, although dominated by the ANN to low frequencies more than in the non-ANSD groups. To high frequencies, the common morphology of ANSD cases was a large CM and summating potential, and small or absent CAP. Common morphologies in other groups were either only a CM, or a combination of CM and CAP. These results indicate that responses to high frequencies, derived primarily from hair cells, are the main source of the CM used to evaluate ANSD in the clinical setting. However, the clinical tests do not capture the wide range of neural activity seen to low frequency sounds

Craniotomy Alone Results in Defalul Mode Network Dysfunction in the Inmature Rat

It remains controversial whether rodents with a craniotomy-only are required, or even appropriate to serve as a sham group to control for the effect of surgery after experimental TBI. Published data show significant molecular and behavioral changes that occur due to craniotomy compared to naïve controls, indicating that craniotomy alone likely constitutes a brain insult. We hypothesized that these confounding effects of craniotomy are also accompanied with alterations in neural circuit dysfunction. We tested this by acquiring resting state functional-MRI data from male, 23 day-old Sprague Dawley rat pups at day 4 post-craniotomy (3mm diameter, -3mm, +4mm left-lateral; intact dura) as well as from age-matched, naïve controls with no craniotomy but with time-matched exposure to isoflurane anesthesia (n= 5/group). Imaging data were acquired on a 7 T Bruker spectrometer using a single-shot, gradient-echo sequence, echo/repetition time: 20/1000ms, 300 repetitions, 128 x 128 matrix, 30 x 30mm field-of-view and 1mm slice-thickness). After typical preprocessing of the time-series data, voxel-wise functional connectivity analysis was then performed by calculating Pearson correlation coefficients between all brain voxels. The Root Mean Square of the correlation values for each voxel were calculated as an index of global functional connectivity (fc), clusterized for the presence of 30 voxels ore more. Large scale, significant (p< 0.01) differences in fc were found between the two groups following group ANOVA. Center of mass for the peaks of the clusters that survived statistical correction for multi voxel comparison were located predominantly in regions previously assigned to the rodent default mode network: bilaterally in auditory, temporal association, and primary visual cortex, and in right retrosplenial cortex and hippocampus. These network alterations provide additional evidence to support the idea that craniotomy-alone constitutes a brain injury, and that it might not always serve as an appropriate control

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

A statistical approach for detecting genomic aberrations in heterogeneous tumor samples from single nucleotide polymorphism genotyping data

We describe a statistical method for the characterization of genomic aberrations in single nucleotide polymorphism microarray data acquired from cancer genomes. Our approach allows us to model the joint effect of polyploidy, normal DNA contamination and intra-tumour heterogeneity within a single unified Bayesian framework. We demonstrate the efficacy of our method on numerous datasets including laboratory generated mixtures of normal-cancer cell lines and real primary tumours

Environmentally Responsible Aviation N plus 2 Advanced Vehicle Study

This is the Northrop Grumman final report for the Environmentally Responsible Aviation (ERA) N+2 Advanced Vehicle Study performed for the National Aeronautics and Space Administration (NASA). Northrop Grumman developed advanced vehicle concepts and associated enabling technologies with a high potential for simultaneously achieving significant reductions in emissions, airport area noise, and fuel consumption for transport aircraft entering service in 2025. A Preferred System Concept (PSC) conceptual design has been completed showing a 42% reduction in fuel burn compared to 1998 technology, and noise 75dB below Stage 4 for a 224- passenger, 8,000 nm cruise transport aircraft. Roadmaps have been developed for the necessary technology maturation to support the PSC. A conceptual design for a 55%-scale demonstrator aircraft to reduce development risk for the PSC has been completed

Brane decay of a (4+n)-dimensional rotating black hole: spin-0 particles

In this work, we study the `scalar channel' of the emission of Hawking radiation from a (4+n)-dimensional, rotating black hole on the brane. We numerically solve both the radial and angular part of the equation of motion for the scalar field, and determine the exact values of the absorption probability and of the spheroidal harmonics, respectively. With these, we calculate the particle, energy and angular momentum emission rates, as well as the angular variation in the flux and power spectra -- a distinctive feature of emission during the spin-down phase of the life of the produced black hole. Our analysis is free from any approximations, with our results being valid for arbitrarily large values of the energy of the emitted particle, angular momentum of the black hole and dimensionality of spacetime. We finally compute the total emissivities for the number of particles, energy and angular momentum and compare their relative behaviour for different values of the parameters of the theory.Comment: 24 pages, 13 figure