Noise kernel for a quantum field in Schwarzschild spacetime under the Gaussian approximation

A method is given to compute an approximation to the noise kernel, defined as the symmetrized connected 2-point function of the stress tensor, for the conformally invariant scalar field in any spacetime conformal to an ultra-static spacetime for the case in which the field is in a thermal state at an arbitrary temperature. The most useful applications of the method are flat space where the approximation is exact and Schwarzschild spacetime where the approximation is better than it is in most other spacetimes. The two points are assumed to be separated in a timelike or spacelike direction. The method involves the use of a Gaussian approximation which is of the same type as that used by Page to compute an approximate form of the stress tensor for this field in Schwarzschild spacetime. All components of the noise kernel have been computed exactly for hot flat space and one component is explicitly displayed. Several components have also been computed for Schwarzschild spacetime and again one component is explicitly displayed.Comment: 34 pages, no figures. Substantial revisions in Secs. I, IV, and V; minor revisions elsewhere; new results include computation of the exact noise kernel for hot flat space and an approximate computation of the noise kernel for a thermal state at an arbitrary temperature in Schwarzschild spacetime when the points are split in the time directio

In Vitro Derived Dendritic Cells trans-Infect CD4 T Cells Primarily with Surface-Bound HIV-1 Virions

In the prevailing model of HIV-1 trans-infection, dendritic cells (DCs) capture and internalize intact virions and transfer these virions to interacting T cells at the virological synapse. Here, we show that HIV-1 virions transmitted in trans from in vitro derived DCs to T cells principally originate from the surface of DCs. Selective neutralization of surface-bound virions abrogated trans-infection by monocyte-derived DCs and CD34-derived Langerhans cells. Under conditions mimicking antigen recognition by the interacting T cells, most transferred virions still derived from the cell surface, although a few were transferred from an internal compartment. Our findings suggest that attachment inhibitors could neutralize trans-infection of T cells by DCs in vivo

Mutational processes of distinct POLE exonuclease domain mutants drive an enrichment of a specific TP53 mutation in colorectal cancer

Author summary Cancer arises through the accumulation of somatic mutations. The way that these somatic mutations form can vary greatly in different cancers. One of the most mutagenic processes that have been identified is caused by mutations within a replicative DNA polymerase known as Polymerase Epsilon (POLE). Cancers with such mutations present with hundreds of thousands of somatic mutations in their genome. Previous cancer genomics studies have identified a number of mutation hotspots in POLE, however how these different POLE mutants behave in affecting mutation distribution has not been studied. Here, we describe the genome-wide mutation profiles of distinct POLE mutant cancers. We find that different mutants indeed result in different mutation profiles and that this can be explained by the different fidelities of these mutants in replicating specific DNA sequences. Significantly, these differences have important implications in cancer formation as we found that a POLE mutation is strongly associated with a specific truncation of the TP53 cancer driver gene. This study furthers our understanding of the POLE mutagenic process in cancer and provide important insights into carcinogenesis in cancers with such mutations.Peer reviewe

Dynamic Microtubules Promote Synaptic NMDA Receptor-Dependent Spine Enlargement

Most excitatory synaptic terminals in the brain impinge on dendritic spines. We and others have recently shown that dynamic microtubules (MTs) enter spines from the dendritic shaft. However, a direct role for MTs in long-lasting spine plasticity has yet to be demonstrated and it remains unclear whether MT-spine invasions are directly influenced by synaptic activity. Lasting changes in spine morphology and synaptic strength can be triggered by activation of synaptic NMDA receptors (NMDARs) and are associated with learning and memory processes. To determine whether MTs are involved in NMDAR-dependent spine plasticity, we imaged MT dynamics and spine morphology in live mouse hippocampal pyramidal neurons before and after acute activation of synaptic NMDARs. Synaptic NMDAR activation promoted MT-spine invasions and lasting increases in spine size, with invaded spines exhibiting significantly faster and more growth than non-invaded spines. Even individual MT invasions triggered rapid increases in spine size that persisted longer following NMDAR activation. Inhibition of either NMDARs or dynamic MTs blocked NMDAR-dependent spine growth. Together these results demonstrate for the first time that MT-spine invasions are positively regulated by signaling through synaptic NMDARs, and contribute to long-lasting structural changes in targeted spines

Visual acuity and contrast sensitivity in preterm and full-term children using a novel digital test

Visual assessment in preverbal children mostly relies on the preferential looking paradigm. It requires an experienced observer to interpret the child’s responses to a stimulus. DIVE (Device for an Integral Visual Examination) is a digital tool with an integrated eye tracker (ET) that lifts this requirement and automatizes this process. The aim of our study was to assess the development of two visual functions, visual acuity (VA) and contrast sensitivity (CS), with DIVE, in a large sample of children from 6 months to 14 years (y) of age, and to compare the results of preterm and full-term children. Participants were recruited in clinical settings from five countries. There were 2208 children tested, 609 of them were born preterm. Both VA and CS improved throughout childhood, with the maximum increase during the first 5 years of age. Gestational age, refractive error and age had an impact on VA results, while CS values were only influenced by age. With this study we report normative reference outcomes for VA and CS throughout childhood and validate the DIVE tests as a useful tool to measure basic visual functions in children

Tunable Multiferroic Properties in Nanocomposite PbTiO\u3csub\u3e3\u3c/sub\u3e-CoFe\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e4\u3c/sub\u3e Epitaxial Thin Films

We report on the synthesis of PbTiO3–CoFe2O4 multiferroic nanocomposites and continuous tuning of their ferroelectric and magnetic properties as a function of the average composition on thin-film composition spreads. The highest dielectric constant and nonlinear dielectric signal was observed at (PbTiO3)85–(CoFe2O4)15, where robust magnetism was also observed. Transmission electron microscopy revealed a pancake-shaped epitaxial nanostructure of PbTiO3 on the order of 30 nm embedded in the matrix of CoFe2O4 at this composition. Composition dependent ferroics properties observed here indicate that there is considerable interdiffusion of cations into each other

Near-Infrared Photometric Survey of Proto-Planetary Nebula Candidates

We present JHK' photometric measurements of 78 objects mostly consisting of proto-planetary nebula candidates. Photometric magnitudes are determined by means of imaging and aperture photometry. Unlike the observations with a photometer with a fixed-sized beam, the method of imaging photometry permits accurate derivation of photometric values because the target sources can be correctly identified and confusion with neighboring sources can be easily avoided. Of the 78 sources observed, we report 10 cases in which the source seems to have been misidentified or confused by nearby bright sources. We also present nearly two dozen cases in which the source seems to have indicated a variability which prompts a follow-up monitoring. There are also a few sources that show previously unreported extendedness. In addition, we present H band finding charts of the target sources.Comment: 3 tables, 1 figur

Bacillus thuringiensis Cry5B protein as a new pan-hookworm cure

Hookworms are intestinal nematode parasites that infect nearly half a billion people and are globally one of the most important contributors to iron-deficiency anemia. These parasites have significant impacts in developing children, pregnant women and working adults. Of all the soil-transmitted helminths or nematodes (STNs), hookworms are by far the most important, with disease burdens conservatively estimated at four million DALYs (Disability-Adjusted Life Years) and with productivity losses of up to US$139 billion annually. To date, mainly one drug, albendazole is used for hookworm therapy in mass drug administration, which has on average approximately 80% cure rate that is lower ( \u3c 40%) in some places. Given the massive numbers of people needing treatment, the threat of parasite resistance, and the inadequacy of current treatments, new and better cures against hookworms are urgently needed. Cry5B, a pore-forming protein produced by the soil bacterium Bacillus thuringiensis (Bt) has demonstrated good efficacy against Ancylostoma ceylanicum hookworm infections in hamsters. Here we broaden studies of Cry5B to include tests against infections of Ancylostoma caninum hookworms in dogs and against infections of the dominant human hookworm, Necator americanus, in hamsters. We show that Cry5B is highly effective against all hookworm parasites tested in all models. Neutralization of stomach acid improves Cry5B efficacy, which will aid in practical application of Cry5B significantly. Importantly, we also demonstrate that the anti-nematode therapeutic efficacy of Cry5B is independent of the host immune system and is not itself negated by repeated dosing. This study indicates that Bt Cry5B is a pan-hookworm anthelmintic with excellent properties for use in humans and other animals

Altered metabolism in cancer

Cancer cells have different metabolic requirements from their normal counterparts. Understanding the consequences of this differential metabolism requires a detailed understanding of glucose metabolism and its relation to energy production in cancer cells. A recent study in BMC Systems Biology by Vasquez et al. developed a mathematical model to assess some features of this altered metabolism. Here, we take a broader look at the regulation of energy metabolism in cancer cells, considering their anabolic as well as catabolic needs