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Predicting Cortical Dark/Bright Asymmetries from Natural Image Statistics and Early Visual Transforms

The nervous system has evolved in an environment with structure and predictability. One of the ubiquitous principles of sensory systems is the creation of circuits that capitalize on this predictability. Previous work has identified predictable non-uniformities in the distributions of basic visual features in natural images that are relevant to the encoding tasks of the visual ...

Uveal Melanoma Cells Utilize a Novel Route for Transendothelial Migration

Uveal melanoma arises in the eye, and it spreads to distant organs in almost half of patients, leading to a fatal outcome. To metastasize, uveal melanoma cells must transmigrate into and out of the microvasculature, crossing the monolayer of endothelial cells that separates the vessel lumen from surrounding tissues. We investigated how human uveal melanoma cells cross the ...

Tipranavir/Ritonavir (500/200 mg and 500/100 mg) Was Virologically Non-Inferior to Lopinavir/Ritonavir (400/100 mg) at Week 48 in Treatment-Naïve HIV-1-Infected Patients: A Randomized, Multinational, Multicenter Trial

Ritonavir-boosted tipranavir (TPV/r) was evaluated as initial therapy in treatment-naïve HIV-1-infected patients because of its potency, unique resistance profile, and high genetic barrier. Trial 1182.33, an open-label, randomized trial, compared two TPV/r dose combinations versus ritonavir-boosted lopinavir (LPV/r). Eligible adults, who had no prior antiretroviral therapy were ...

Role of Cortactin Homolog HS1 in Transendothelial Migration of Natural Killer Cells

Natural Killer (NK) cells perform many functions that depend on actin assembly, including adhesion, chemotaxis, lytic synapse assembly and cytolysis. HS1, the hematopoietic homolog of cortactin, binds to Arp2/3 complex and promotes actin assembly by helping to form and stabilize actin filament branches. We investigated the role of HS1 in transendothelial migration (TEM) by NK ...

Impaired Mitochondrial Energy Production Causes Light-Induced Photoreceptor Degeneration Independent of Oxidative Stress

Two insults often underlie a variety of eye diseases including glaucoma, optic atrophy, and retinal degeneration—defects in mitochondrial function and aberrant Rhodopsin trafficking. Although mitochondrial defects are often associated with oxidative stress, they have not been linked to Rhodopsin trafficking. In an unbiased forward genetic screen designed to isolate mutations that ...

Clinical Utility of a Coronary Heart Disease Risk Prediction Gene Score in UK Healthy Middle Aged Men and in the Pakistani Population

Background Numerous risk prediction algorithms based on conventional risk factors for Coronary Heart Disease (CHD) are available but provide only modest discrimination. The inclusion of genetic information may improve clinical utility. Methods We tested the use of two gene scores (GS) in the prospective second Northwick Park Heart Study (NPHSII) of 2775 healthy UK men (284 cases), ...

How Accurate Is MOLLI T1 Mapping In Vivo? Validation by Spin Echo Methods

T1 mapping is a promising quantitative tool for assessing diffuse cardiomyopathies. The purpose of this study is to quantify in vivo accuracy of the Modified Look-Locker Inversion Recovery (MOLLI) cardiac T1 mapping sequence against the spin echo gold standard, which has not been done previously. T1 accuracy of MOLLI was determined by comparing with the gold standard inversion ...

You Turn Me Cold: Evidence for Temperature Contagion

Introduction During social interactions, our own physiological responses influence those of others. Synchronization of physiological (and behavioural) responses can facilitate emotional understanding and group coherence through inter-subjectivity. Here we investigate if observing cues indicating a change in another's body temperature results in a corresponding temperature change in ...

Correction: Raltegravir Non-Inferior to Nucleoside Based Regimens in SECOND-LINE Therapy with Lopinavir/Ritonavir over 96 Weeks: A Randomised Open Label Study for the Treatment Of HIV-1 Infection

. Sohn Hedy Teppler Boris Renjifo Jean-Michel Molina Sean Emery David A. Cooper SECOND-LINE - The group author, SECOND-LINE, was omitted from the author byline and should be listed as the fifteenth

Effect of the PPARG2 Pro12Ala Polymorphism on Associations of Physical Activity and Sedentary Time with Markers of Insulin Sensitivity in Those with an Elevated Risk of Type 2 Diabetes

Background Peroxisome proliferator-activated receptor gamma (PPARγ) is an important regulator of metabolic health and a common polymorphism in the PPAR-γ2 gene (PPARG2) may modify associations between lifestyle behaviour and health. Objective To investigate whether the PPARG2 Pro12Ala genotype modifies the associations of sedentary behaviour and moderate-to-vigorous intensity ...

HLA Alleles Association with Changes in Bone Mineral Density in HIV-1-Infected Adults Changing Treatment to Tenofovir-Emtricitabine or Abacavir-Lamivudine

Background There are limited data regarding the influence of human leukocyte antigen (HLA) polymorphisms on reduced bone mineral density (BMD). We investigated the relationship between HLA supertypes and BMD in HIV-infected adults changing their existing treatment to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) in the STEAL study. Methods Lumbar spine and ...

HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5-8 Days—Implications for HIV Remission

HIV infection can be effectively controlled by anti-retroviral therapy (ART) in most patients. However therapy must be continued for life, because interruption of ART leads to rapid recrudescence of infection from long-lived latently infected cells. A number of approaches are currently being developed to ‘purge’ the reservoir of latently infected cells in order to either eliminate ...

Moving Away from Ritonavir, Abacavir, Tenofovir, and Efavirenz (RATE) - Agents That Concern Prescribers and Patients: A Feasibility Study and Call for a Trial

Objectives Regimens sparing RATE (ritonavir, abacavir, tenofovir, efavirienz) agents might have better long-term safety. We conducted a feasibility exercise to assess the potential for a randomised trial evaluating RATE-sparing regimens. Design Observational. Methods We first calculated RATE-sparing options available to an average patient receiving RATE agents. We reviewed ...

Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment

A newer generation of anti-cancer drugs targeting underlying somatic genetic driver events have resulted in high single-agent or single-pathway response rates in selected patients, but few patients achieve complete responses and a sizeable fraction of patients relapse within a year. Thus, there is a pressing need for identification of combinations of targeted agents which induce ...

Raltegravir Non-Inferior to Nucleoside Based Regimens in SECOND-LINE Therapy with Lopinavir/Ritonavir over 96 Weeks: A Randomised Open Label Study for the Treatment Of HIV-1 Infection

Objective To determine the durability over 96 weeks of safety and efficacy of lopinavir/ritonavir (LPV/r) and raltegravir (RAL) which was demonstrated to have non-inferior efficacy relative to a regimen of LPV/r with nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) (Control) in primary analysis at 48 weeks. Design Open label, centrally randomised trial. Setting ...

Differences in the Direction of Change of Cerebral Function Parameters Are Evident over Three Years in HIV-Infected Individuals Electively Commencing Initial cART

from Abbott, Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck Sharp and Dohme, Roche, IDS, Bayer Schering and Merck Serono. David A. Cooper has received honoraria, consultancies and

Explaining the Determinants of First Phase HIV Decay Dynamics through the Effects of Stage-dependent Drug Action

A recent investigation of the effect of different antiretroviral drug classes on first phase dynamics of HIV RNA plasma virus levels has indicated that drugs acting at stages closer to viral production, such as the integrase inhibitor raltegravir, can produce a steeper first phase decay slope that may not be due to drug efficacy. Moreover it was found that for most drug classes the ...

Consuming Transgenic Goats' Milk Containing the Antimicrobial Protein Lysozyme Helps Resolve Diarrhea in Young Pigs

Childhood diarrhea is a significant problem in many developing countries and E. coli is a main causative agent of diarrhea in young children. Lysozyme is an antimicrobial protein highly expressed in human milk, but not ruminant milk, and is thought to help protect breastfeeding children against diarrheal diseases. We hypothesized that consumption of milk from transgenic goats which ...

HIV Lipodystrophy in Participants Randomised to Lopinavir/Ritonavir (LPV/r) +2–3 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (N(t)RTI) or LPV/r + Raltegravir as Second-Line Antiretroviral Therapy

Objective To compare changes over 48 weeks in body fat, lipids, Metabolic Syndrome and cardiovascular disease risk between patients randomised 1∶1 to lopinavir/ritonavir (r/LPV) plus raltegravir (RAL) compared to r/LPV plus 2–3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second-line therapy. Methods Participants were HIV-1 positive (>16 years) failing ...