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The problem of how complex quantum systems eventually come to rest lies at the heart of statistical mechanics. The maximum-entropy principle describes which quantum states can be expected in equilibrium, but not how closed quantum many-body systems dynamically equilibrate. Here, we report the experimental observation of the non-equilibrium dynamics of a density wave of ultracold bosonic atoms in an optical lattice in the regime of strong correlations. Using an optical superlattice, we follow its dynamics in terms of quasi-local densities, currents and coherences-all showing a fast relaxation towards equilibrium values. Numerical calculations based on matrix-product states are in an excellent quantitative agreement with the experimental data. The system fulfills the promise of being a dynamical quantum simulator, in that the controlled dynamics runs for longer times than present classical algorithms can keep track of.
Optical control of magnetization using femtosecond laser without applying any external magnetic field offers the advantage of switching magnetic states at ultrashort time scales. Recently, all-optical helicity-dependent switching (AO-HDS) has drawn a significant attention for potential information and data storage device applications. In this work, we employ element and magnetization sensitive photoemission electron microscopy (PEEM) to investigate the role of heating in AO-HDS for thin films of the rare-earth transition-metal alloy TbFe. Spatially resolved measurements in a 3–5 μm sized stationary laser spot demonstrate that AO-HDS is a local phenomenon in the vicinity of thermal demagnetization in a ‘ring’ shaped region. The efficiency of AO-HDS further depends on a local temperature profile around the demagnetized region and thermally activated domain wall motion. We also demonstrate that the thickness of the film determines the preferential switching direction for a particular helicity.
We combine HST imaging from the GEMS ( Galaxy Evolution from Morphologies and SEDs) survey with photometric redshifts from COMBO-17 to explore the evolution of disk-dominated galaxies since z less than or similar to 1.1. The sample is composed of all GEMS galaxies with Sersic indices n < 2.5, derived from fits to the galaxy images. We account fully for selection effects through careful analysis of image simulations; we are limited by the depth of the redshift and HST data to the study of galaxies with M-V less than or similar to -20, or equivalently, log (M/M-circle dot) greater than or similar to 10. We find strong evolution in the magnitude-size scaling relation for galaxies with M-V less than or similar to -20, corresponding to a brightening of similar to 1 mag arcsec(-2) in rest-frame V band by z similar to 1. Yet disks at a given absolute magnitude are bluer and have lower stellar mass-to-light ratios at z similar to 1 than at the present day. As a result, our findings indicate weak or no evolution in the relation between stellar mass and effective disk size for galaxies with log (M/M-circle dot) greater than or similar to 10 over the same time interval. This is strongly inconsistent with the most naive theoretical expectation, in which disk size scales in proportion to the halo virial radius, which would predict that disks are a factor of 2 denser at fixed mass at z similar to 1. The lack of evolution in the stellar mass-size relation is consistent with an "inside-out'' growth of galaxy disks on average (galaxies increasing in size as they grow more massive), although we cannot rule out more complex evolutionary scenarios
We have performed Hubble Space Telescope imaging of a sample of 23 high-redshift (1.8<z<2.75) active galactic nuclei (AGNs), drawn from the COMBO-17 survey. The sample contains moderately luminous quasars (M(B)similar to-23). The data are part of the Galaxy Evolution from Morphologies and SEDs imaging survey that provides high-resolution optical images obtained with the Advanced Camera for Surveys in two bands (F606W and F850LP), sampling the rest-frame UV flux of the targets. To deblend the AGN images into nuclear and resolved (host galaxy) components, we use a point-spread function subtraction technique that is strictly conservative with respect to the flux of the host galaxy. We resolve the host galaxies in both filter bands in nine of the 23 AGNs, whereas the remaining 14 objects are considered nondetections, with upper limits of less than 5% of the nuclear flux. However, when we co-add the unresolved AGN images into a single high signal-to-noise ratio composite image, we find again an unambiguously resolved host galaxy. The recovered host galaxies have apparent magnitudes of 23.0<F606W<26.0 and 22.5<F850LP<24.5, with rest-frame UV colors in the range -0.2<(F606W-F850LP)(obs)<2.3. The rest-frame absolute magnitudes at 200 nm are -20.0<M-200 nm<-22.2. The photometric properties of the composite host are consistent with the individual resolved host galaxies. We find that the UV colors of all host galaxies are substantially bluer than expected from an old population of stars with formation redshift z<=5, independent of the assumed metallicities. These UV colors and luminosities range up to the values found for Lyman break galaxies (LBGs) at z=3. Our results suggest either a recent starburst of, e. g., a few percent of the total stellar mass at 100 Myr before observation, with mass fraction and age strongly degenerate, or the possibility that the detected UV emission may be due to young stars forming continuously. For the latter case we estimate star formation rates of typically &SIM;6 M&ODOT; yr(-1) (uncorrected for internal dust attenuation), which again lies in the range of rates implied from the UV flux of LBGs. Our results agree with the recent discovery of enhanced blue stellar light in AGN hosts at lower redshifts
We present the results from a study of the host galaxies of 15 optically selected active galactic nuclei (AGNs) with 0.5<z<1.1 from the Galaxy Evolution from Morphology and SEDs project (GEMS). GEMS is a Hubble Space Telescope imaging survey of a similar to28' x 28' contiguous field centered on the Chandra Deep Field-South in the F606W and F850LP filter bands. It incorporates the spectral energy distributions and redshifts of similar to10,000 objects, obtained by the COMBO-17 project. We have detected the host galaxies of all 15 AGNs in the F850LP band (and 13 of 15 in the F606W band), recovering their fluxes, morphologies, and structural parameters. We find that 80% of the host galaxies have early-type (bulge-dominated) morphologies, while the rest have structures characteristic of late-type (disk-dominated) galaxies. We find that 25% of the early types and 30% of the late types exhibit disturbances consistent with galaxy interactions. The hosts show a wide range of colors, from those of red-sequence galaxies to blue colors consistent with ongoing star formation. Roughly 70% of the morphologically early-type hosts have rest-frame blue colors, a much larger fraction than those typical of nonactive morphologically early-type galaxies in this redshift and luminosity range. Yet, we find that the early-type hosts are structurally similar to red-sequence elliptical galaxies, inasmuch as they follow an absolute magnitude versus half-light size correlation that is consistent with the mean relation for early-type galaxies at similar redshifts
Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
(2020)
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
We report the discovery of six spatially extended (10-100 kpc) line-emitting nebulae in the z approximate to 0.57 galaxy group hosting PKS 0405-123, one of the most luminous quasars at z < 1. The discovery is enabled by the Multi Unit Spectroscopic Explorer and provides tantalizing evidence connecting large-scale gas streams with nuclear activity on scales of <10 proper kpc (pkpc). One of the nebulae exhibits a narrow, filamentary morphology extending over 50 pkpc toward the quasar with narrow internal velocity dispersion (50 km s(-1)) and is not associated with any detected galaxies, consistent with a cool intragroup medium filament. Two of the nebulae are 10 pkpc north and south of the quasar with tidal-arm-like morphologies. These two nebulae, along with a continuum-emitting arm extending 60 pkpc from the quasar, are signatures of interactions that are expected to redistribute angular momentum in the host interstellar medium (ISM) to facilitate star formation and quasar fueling in the nucleus. The three remaining nebulae are among the largest and most luminous [O III] emitting "blobs" known (1400-2400 pkpc(2)) and correspond both kinematically and morphologically to interacting galaxy pairs in the quasar host group, consistent with arising from stripped ISM rather than large-scale quasar outflows. The presence of these large- and small-scale nebulae in the vicinity of a luminous quasar bears significantly on the effect of large-scale environment on galaxy and black hole fueling, providing a natural explanation for the previously known correlation between quasar luminosity and cool circumgalactic medium.
High storage density magnetic devices rely on the precise, reliable and ultrafast switching times of the magnetic states. Optical control of magnetization using femtosecond laser without applying any external magnetic field offers the advantage of switching magnetic states at ultrashort time scales, which has attracted a significant attention. Recently, it has been reported and demonstrated the,so-called, all-optical helicity-dependent switching (AO-HDS) in which a circularly polarized femtosecond laser pulse switches the magnetization of a ferromagnetic thin film as function of laser helicity [1]. Afterward, in more recent studies, it has been reported that AO-HDS is a general phenomenon existing in magnetic materials ranging from rare earth - transition metals ferrimagnetic (e.g. alloys, multilayers and hetero-structures system) to even ferromagnetic thin films. Among numerous studies in the literature which are discussing the microscopic origin of AO-HDS in ferromagnets or ferrimagnetic alloys, the most renowned concepts are momentum transfer via Inverse Faraday Effect (IFE) [1-3]and the concept of preferential thermal demagnetization for one magnetization direction by heating close to Tc (Curie temperature) in the presence of magnetic circular dichroism (MCD) [4-6]. In this study, we investigate all-optical magnetic switching using a stationary femtosecond laser spot (3-5 μm) in TbFe alloys via photoemission electron microscopy (PEEM) and x-ray magnetic circular dichroism (XMCD) with a spatial resolution of approximately 30 nm. We spatially characterize the effect of laser heating and local temperature profile created across the laser spot on AO-HDS in TbFe thin films. We find that AO-HDS occurs only in a `ring' shaped region surrounding the thermally demagnetized region formed by the laser spot and the formation of switched domains relies further on thermally induced domain wall motion. Our temperature dependent measurements highlight the importance of attainin...
This paper presents a study of the galactic environment of a chemically pristine (<0.6 per cent solar metallicity) Lyman Limit system (LLS) discovered along the sightline towards QSO SDSSJ 135726.27+043541.4 (Z(QSO) = 1.233) at projected distance d = 126 physical kpc (pkpc) from a luminous red galaxy (LRG) at z = 0.33. Combining deep Hubble Space Telescope images, MUSE integral field spectroscopic data, and wide-field redshift survey data has enabled an unprecedented, ultradeep view of the environment around this LRG-LLS pair. A total of 12 galaxies, including the LRG, are found at d less than or similar to 400 pkpc and line-of-sight velocity Delta v < 600 km S-1 of the LLS, with intrinsic luminosity ranging from 0.001 L-* to 2 L-* and a corresponding stellar mass range of M-star approximate to 10(7-11) M-circle dot. All 12 galaxies contribute to a total mass of M-star = 1.6 x 10(11) M-circle dot with approximate to 80 per cent contained in the LRG. The line-of-sight velocity dispersion of these galaxies is found to be sigma (group) = 230 km s(-1) with the centre of mass at d(group) = 118 pkpc and line-of-sight velocity offset of Delta v(group) = 181 km s(-1) from the LLS. Three of these are located at d less than or similar to 100 pkpc from the LLS, and they are all faint with intrinsic luminosity less than or similar to 0.02 L-* and gas-phase metallicity of approximate to 10 per cent solar in their interstellar medium. The disparity in the chemical enrichment level between the LLS and the group members suggests that the LLS originates in infalling intergalactic medium and that parts of the intergalactic gas near old and massive galaxies can still remain chemically pristine through the not too distant past.
Genome-wide association analysis in humans links nucleotide metabolism to leukocyte telomere length
(2020)
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1 , PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Permanent genetic resources added to molecular ecology resources database 1 April 2011-31 May 2011
(2011)
This article documents the addition of 92 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Anopheles minimus, An. sinensis, An. dirus, Calephelis mutica, Lutjanus kasmira, Murella muralis and Orchestia montagui. These loci were cross-tested on the following species: Calephelis arizonensi, Calephelis borealis, Calephelis nemesis, Calephelis virginiensis and Lutjanus bengalensis.
Morphological and genetic evidence for early Holocene cattle management in northeastern China
(2013)
The domestication of cattle is generally accepted to have taken place in two independent centres: around 10,500 years ago in the Near East, giving rise to modern taurine cattle, and two millennia later in southern Asia, giving rise to zebu cattle. Here we provide firmly dated morphological and genetic evidence for early Holocene management of taurine cattle in northeastern China. We describe conjoining mandibles from this region that show evidence of oral stereotypy, dated to the early Holocene by two independent C-14 dates. Using Illumina high-throughput sequencing coupled with DNA hybridization capture, we characterize 15,406 bp of the mitogenome with on average 16.7-fold coverage. Phylogenetic analyses reveal a hitherto unknown mitochondrial haplogroup that falls outside the known taurine diversity. Our data suggest that the first attempts to manage cattle in northern China predate the introduction of domestic cattle that gave rise to the current stock by several thousand years.
A light source that emits single photons at well-defined times and into a well-defined mode would be a decisive asset for quantum information processing, quantum metrology, and sub-shot-noise detection of absorption. One of the central challenges in the realization of such a deterministic device based on a single quantum emitter concerns the collection of the photons, which are radiated into a 4 pi solid angle. Here, we present the fabrication and characterization of an optical antenna designed to convert the dipolar radiation of an arbitrarily oriented quantum emitter to a directional beam with more than 99% efficiency. Our approach is extremely versatile and can be used for more efficient detection of nanoscopic emitters ranging from semiconductor quantum dots to dye molecules, color centers, or rare-earth ions in various environments. Having addressed the issue of collection efficiency, we also discuss the photophysical limitations of the existing quantum emitters for the realization of a deterministic single-photon source. (C) 2014 Optical Society of America
The ability of some plant species to dominate communities in new biogeographical ranges has been attributed to an innate higher competitive ability and release from co-evolved specialist enemies. Specifically, invasive success in the new range might be explained by release from biotic negative soil-feedbacks, which control potentially dominant species in their native range. To test this hypothesis, we grew individuals from sixteen phylogenetically paired European grassland species that became either invasive or naturalized in new ranges, in either sterilized soil or in sterilized soil with unsterilized soil inoculum from their native home range. We found that although the native members of invasive species generally performed better than those of naturalized species, these native members of invasive species also responded more negatively to native soil inoculum than did the native members of naturalized species. This supports our hypothesis that potentially invasive species in their native range are held in check by negative soil-feedbacks. However, contrary to expectation, negative soil-feedbacks in potentially invasive species were not much increased by interspecific competition. There was no significant variation among families between invasive and naturalized species regarding their feedback response (negative vs. neutral). Therefore, we conclude that the observed negative soil feedbacks in potentially invasive species may be quite widespread in European families of typical grassland species.
Light-switchable proteins offer numerous opportunities as tools for manipulating biological systems with exceptional degrees of spatiotemporal control. Most designed light-switchable proteins currently in use have not been optimised using the randomisation and selection/screening approaches that are widely used in other areas of protein engineering. Here we report an approach for screening light-switchable DNA-binding proteins that relies on light-dependent repression of the transcription of a fluorescent reporter. We demonstrate that the method can be used to recover a known light-switchable DNA-binding protein from a random library.
Objective. We evaluated the long-term effect of a smoking intervention embedded in an adherence program in patients with an increased risk for cardiovascular disease.
Method. Secondary analysis of a randomized controlled trial: In 2002-2004,8108 patients with hypercholesterolemia were enrolled from general practices in Germany. Patients received a 12-month adherence program and statin medication (intervention) or statin medication only (control). The program aimed to improve adherence to medication and lifestyle by educational material, mailings, and phone calls. Smoking was self-reported at baseline and every 6 months during the 3-year follow-up.
Results. In total, 7640 patients were analyzed. At baseline, smoking prevalence was 21.7% in the intervention and 21.5% in the control group. Prevalence decreased in both groups to 16.6% vs. 19.5%, 153% vs. 16.8%, and 14.2% vs. 15.6% at the 12-, 24-, and 36-month follow-up. The intervention had a beneficial effect on smoking differing over time (group x time: P = 0.005). The effect was largest after 6 and 12 months [odds ratios (95% confidence intervals): 0.67 (0.54-0.82) and 0.63 (0.51-0.78)]. The effect decreased until the 18-month follow-up [0.72 (0.58-0.90)] and was not significant after 24 months.
Conclusion. A low-intensity smoking intervention embedded in an adherence program can contribute to smoking cessation although the intervention effect diminished over time. (C) 2015 Elsevier Inc. All rights reserved.
Numerous (meta-)gabbroic dikes or stocks occur within the latest Neoproterozoic-early Cambrian series of the Menderes Massif (Anatolide-Tauride Block, western Turkey). These well-preserved rocks were locally converted into eclogitic metagabbros and garnet amphibolites along the contacts or shear zones. Both bulk-rock composition and compositions of igneous clinopyroxenes suggest continental tholeiitic affinity. U-Pb dating of igneous zircons from gabbroic rocks yielded a mean age of 563 +/- 1 Ma (2 sigma), indicating emplacement during the latest Neoproterozoic (Ediacaran). On the other hand, rims of zircons from eclogitic metagabbro gave 535 +/- 3 Ma (2 sigma) (early Cambrian), in addition to 558 +/- 3 Ma (2 sigma) obtained from the igneous core of zircons. These ages are interpreted as the time of high-P metamorphism and crystallization age of gabbroic protolith, respectively. Given the estimated paleogeographic position of the Anatolide-Tauride Block during the late Neoproterozoic and early Cambrian, this orogenic event can be spatially and temporally related to the northward continuity of 600-500 Ma orogenic event (Malagasy/Kuunga orogeny) extending from western margin of India, Madagascar, via Arabia up to northern margin of Gondwana beneath thick Phanerozoic cover series in Arabian Peninsula. Therefore, the high-P evolution of the basement of the Menderes Massif and associated basic intrusions can be interpreted to mark the latest stages of consumption of the basin/oceanic branches and final amalgamation of the Gondwana during the late Neoproterozoic-early Cambrian around the Arabian region. (C) 2015 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.
Numerical simulation of fluid-flow processes in a 3D high-resolution carbonate reservoir analogue
(2014)
A high-resolution three-dimensional (3D) outcrop model of a Jurassic carbonate ramp was used in order to perform a series of detailed and systematic flow simulations. The aim of this study was to test the impact of small- and large-scale geological features on reservoir performance and oil recovery. The digital outcrop model contains a wide range of sedimentological, diagenetic and structural features, including discontinuity surfaces, shoal bodies, mud mounds, oyster bioherms and fractures. Flow simulations are performed for numerical well testing and secondary oil recovery. Numerical well testing enables synthetic but systematic pressure responses to be generated for different geological features observed in the outcrops. This allows us to assess and rank the relative impact of specific geological features on reservoir performance. The outcome documents that, owing to the realistic representation of matrix heterogeneity, most diagenetic and structural features cannot be linked to a unique pressure signature. Instead, reservoir performance is controlled by subseismic faults and oyster bioherms acting as thief zones. Numerical simulations of secondary recovery processes reveal strong channelling of fluid flow into high-permeability layers as the primary control for oil recovery. However, appropriate reservoir-engineering solutions, such as optimizing well placement and injection fluid, can reduce channelling and increase oil recovery.
Along the NE Pamir margin, flights of late Quaternary fluvial terraces span actively deforming fault-related folds. We present detailed results on two terraces dated using optically stimulated luminescence (OSL) and cosmogenic radionuclide Be-10 (CRN) techniques. Quartz OSL dating of two different grain sizes (4-11 mu m and 90-180 mu m) revealed the fine-grain quartz fraction may overestimate the terrace ages by up to a factor of ten. Two-mm, small-aliquot, coarse-grain quartz OSL ages, calculated using the minimum age model, yielded stratigraphically consistent ages within error and dated times of terrace deposition to similar to 9 and similar to 16 ka. We speculate that, in this arid environment, fine-grain samples can be transported and deposited in single, turbid, and (sometimes) night-time floods that prevent thorough bleaching and, thereby, can lead to relatively large residual OSL signals. In contrast, sand in the fluvial system is likely to have a much longer residence time during transport, thereby providing greater opportunities for thorough bleaching. CRN Be-10 depth profiles date the timing of terrace abandonment to similar to 8 and similar to 14 ka: ages that generally agree with the coarse-grain quartz OSL ages. Our new terrace age of similar to 13-14 ka is broadly consistent with other terraces in the region that indicate terrace deposition and subsequent abandonment occurred primarily during glacial-interglacial transitions, thereby suggesting a climatic control on the formation of these terraces on the margins of the Tarim Basin. Furthermore, tectonic shortening rates calculated from these deformed terraces range from similar to 1.2 to similar to 4.6 mm/a and, when combined with shortening rates from other structures in the region, illuminate the late Quaternary basinward migration of deformation to faults and folds along the Pamir-Tian Shan collisional interface.
Piggyback basins on the margins of growing orogens commonly serve as sensitive recorders of the onset of thrust deformation and changes in source areas. The Bieertuokuoyi piggyback basin, located in the hanging wall of the Pamir Frontal Thrust, provides an unambiguous record of the outward growth of the northeast Pamir margin in northwest China from the Miocene through the Quaternary. To reconstruct the deformation along the margin, we synthesized structural mapping, stratigraphy, magnetostratigraphy, and cosmogenic burial dating of basin fill and growth strata. The Bieertuokuoyi basin records the initiation of the Pamir Frontal Thrust and the Takegai Thrust similar to 5-6Ma, as well as clast provenance and paleocurrent changes resulting from the Pliocene-to-Recent uplift and exhumation of the Pamir to the south. Our results show that coeval deformation was accommodated on the major structures on the northeast Pamir margin throughout the Miocene to Recent. Furthermore, our data support a change in the regional kinematics around the Miocene-Pliocene boundary (similar to 5-6Ma). Rapid exhumation of NE Pamir extensional domes, coupled with cessation of the Kashgar-Yecheng Transfer System on the eastern margin of the Pamir, accelerated the outward propagation of the northeastern Pamir margin and the southward propagation of the Kashi-Atushi fold-and-thrust belt in the southern Tian Shan. This coeval deformation signifies the coupling of the Pamir and Tarim blocks and the transfer of shortening north to the Pamir frontal faults and across the quasi-rigid Tarim Basin to the southern Tian Shan Kashi-Atushi fold-and-thrust system.
Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin expression in C-elegans
(2015)
Pak choi (Brassica rapa subsp. chinensis) is a leafy vegetable that is widely available in Asia and consumed in rising quantities in Europe. Pak choi contains high levels of secondary plant metabolites, such as carotenoids, chlorophylls, glucosinolates, phenolic compounds, and vitamin K, which are beneficial for humans if consumed on a regular basis. The evaluation of the genotype-induced variation of secondary plant metabolites revealed that the cultivar ‘Amur’ contained the highest concentration of secondary plant metabolites. Furthermore, steaming retained more chlorophylls, glucosinolates, phenolic acids and flavonoid compounds than boiling. In contrast, both domestic cooking methods – boiling, and steaming – reduced the formation of glucosinolate breakdown products, especially the undesired epithionitriles and nitriles but less of the health-beneficial isothiocyanates.
Loss of pdr-1/parkin influences Mn homeostasis through altered ferroportin expression in C. elegans
(2015)
Overexposure to the essential metal manganese (Mn) can result in an irreversible condition known as manganism that shares similar pathophysiology with Parkinson's disease (PD), including dopaminergic (DAergic) cell loss that leads to motor and cognitive impairments. However, the mechanisms behind this neurotoxicity and its relationship with PD remain unclear. Many genes confer risk for autosomal recessive, early-onset PD, including the parkin/PARK2 gene that encodes for the E3 ubiquitin ligase Parkin. Using Caenorhabditis elegans (C. elegans) as an invertebrate model that conserves the DAergic system, we previously reported significantly increased Mn accumulation in pdr-1/parkin mutants compared to wildtype (WT) animals. For the current study, we hypothesize that this enhanced accumulation is due to alterations in Mn transport in the pdr-1 mutants. While no change in mRNA expression of the major Mn importer proteins (smf-1-3) was found in pdr-1 mutants, significant downregulation in mRNA levels of the putative Mn exporter ferroportin (fpn-1.1) was observed. Using a strain overexpressing fpn-1.1 in worms lacking pdr-1, we show evidence for attenuation of several endpoints of Mn-induced toxicity, including survival, metal accumulation, mitochondrial copy number and DAergic integrity, compared to pdr-1 mutants alone. These changes suggest a novel role of pdr-1 in modulating Mn export through altered transporter expression, and provides further support of metal dyshomeostasis as a component of Parkinsonism pathophysiology.
Instruments for measuring the absorbed dose and dose rate under radiation exposure, known as radiation dosimeters, are indispensable in space missions. They are composed of radiation sensors that generate current or voltage response when exposed to ionizing radiation, and processing electronics for computing the absorbed dose and dose rate. Among a wide range of existing radiation sensors, the Radiation Sensitive Field Effect Transistors (RADFETs) have unique advantages for absorbed dose measurement, and a proven record of successful exploitation in space missions. It has been shown that the RADFETs may be also used for the dose rate monitoring. In that regard, we propose a unique design concept that supports the simultaneous operation of a single RADFET as absorbed dose and dose rate monitor. This enables to reduce the cost of implementation, since the need for other types of radiation sensors can be minimized or eliminated. For processing the RADFET's response we propose a readout system composed of analog signal conditioner (ASC) and a self-adaptive multiprocessing system-on-chip (MPSoC). The soft error rate of MPSoC is monitored in real time with embedded sensors, allowing the autonomous switching between three operating modes (high-performance, de-stress and fault-tolerant), according to the application requirements and radiation conditions.
Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER) stress, autophagy dysregulation, apoptosis, and disruption of other metal homeostasis. The mechanisms of Mn homeostasis are not fully understood. Here, we will address recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells. We will conclude with recommendations for future research areas on Mn metabolism.
Photogeneration, recombination, and transport of free charge carriers in all-polymer bulk heterojunction solar cells incorporating poly(3-hexylthiophene) (P3HT) as donor and poly([N,N'-bis(2-octyldodecyl)-naphthelene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5'-(2,2'-bithiophene)) (P(NDI2OD-T2)) as acceptor polymer have been investigated by the use of time delayed collection field (TDCF) and time-of-flight (TOF) measurements. Depending on the preparation procedure used to dry the active layers, these solar cells comprise high fill factors (FFs) of up to 67%. A strongly reduced bimolecular recombination (BMR), as well as a field-independent free charge carrier generation are observed, features that are common to high performance fullerene-based solar cells. Resonant soft X-ray measurements (R-SoXS) and photoluminescence quenching experiments (PQE) reveal that the BMR is related to domain purity. Our results elucidate the similarities of this polymeric acceptor with the superior recombination properties of fullerene acceptors.
Pavlovian-to-instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high-risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18-year-old male adults. Participants (N = 191) were instructed to 'collect good shells' and 'leave bad shells' during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high-risk and low-risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high-risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high-risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High-risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom-up), decreased lPFC response (top-down), and their altered interplay may contribute to poor interference control in the high-risk drinkers.
Pavlovian cues can influence ongoing instrumental behaviour via Pavlovian-to-instrumental transfer (PIT) processes. While appetitive Pavlovian cues tend to promote instrumental approach, they are detrimental when avoidance behaviour is required, and vice versa for aversive cues. We recently reported that susceptibility to interference between Pavlovian and instrumental control assessed via a PIT task was associated with risky alcohol use at age 18. We now investigated whether such susceptibility also predicts drinking trajectories until age 24, based on AUDIT (Alcohol Use Disorders Identification Test) consumption and binge drinking (gramme alcohol/drinking occasion) scores. The interference PIT effect, assessed at ages 18 and 21 during fMRI, was characterized by increased error rates (ER) and enhanced neural responses in the ventral striatum (VS), the lateral and dorsomedial prefrontal cortices (dmPFC) during conflict, that is, when an instrumental approach was required in the presence of an aversive Pavlovian cue or vice versa. We found that a stronger VS response during conflict at age 18 was associated with a higher starting point of both drinking trajectories but predicted a decrease in binge drinking. At age 21, high ER and enhanced neural responses in the dmPFC were associated with increasing AUDIT-C scores over the next 3 years until age 24. Overall, susceptibility to interference between Pavlovian and instrumental control might be viewed as a predisposing mechanism towards hazardous alcohol use during young adulthood, and the identified high-risk group may profit from targeted interventions.
Background:
Prejudices against minorities can be understood as habitually negative evaluations that are kept in spite of evidence to the contrary. Therefore, individuals with strong prejudices might be dominated by habitual or "automatic" reactions at the expense of more controlled reactions. Computational theories suggest individual differences in the balance between habitual/model-free and deliberative/model-based decision-making.
Methods:
127 subjects performed the two Step task and completed the blatant and subtle prejudice scale.
Results:
By using analyses of choices and reaction times in combination with computational modeling, subjects with stronger blatant prejudices showed a shift away from model-based control. There was no association between these decision-making processes and subtle prejudices.
Conclusion:
These results support the idea that blatant prejudices toward minorities are related to a relative dominance of habitual decision-making. This finding has important implications for developing interventions that target to change prejudices across societies.
Background:
Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associatedwith worse outcomes. However, AKI among hospitalized patients with COVID19 in the United States is not well described.
Methods:
This retrospective, observational study involved a review of data from electronic health records of patients aged >= 18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality.
Results:
Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patientswith AKI required dialysis. The proportionswith stages 1, 2, or 3 AKIwere 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up.
Conclusions:
AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.
Pavlovian-to-instrumental transfer (PIT) tasks examine the influence of Pavlovian stimuli on ongoing instrumental behaviour. Previous studies reported associations between a strong PIT effect, high-risk drinking and alcohol use disorder. This study investigated whether susceptibility to interference between Pavlovian and instrumental control is linked to risky alcohol use in a community sample of 18-year-old male adults. Participants (N = 191) were instructed to 'collect good shells' and 'leave bad shells' during the presentation of appetitive (monetary reward), aversive (monetary loss) or neutral Pavlovian stimuli. We compared instrumental error rates (ER) and functional magnetic resonance imaging (fMRI) brain responses between the congruent and incongruent conditions, as well as among high-risk and low-risk drinking groups. On average, individuals showed a substantial PIT effect, that is, increased ER when Pavlovian cues and instrumental stimuli were in conflict compared with congruent trials. Neural PIT correlates were found in the ventral striatum and the dorsomedial and lateral prefrontal cortices (lPFC). Importantly, high-risk drinking was associated with a stronger behavioural PIT effect, a decreased lPFC response and an increased neural response in the ventral striatum on the trend level. Moreover, high-risk drinkers showed weaker connectivity from the ventral striatum to the lPFC during incongruent trials. Our study links interference during PIT to drinking behaviour in healthy, young adults. High-risk drinkers showed higher susceptibility to Pavlovian cues, especially when they conflicted with instrumental behaviour, indicating lower interference control abilities. Increased activity in the ventral striatum (bottom-up), decreased lPFC response (top-down), and their altered interplay may contribute to poor interference control in the high-risk drinkers.
Background Host factors such as angiotensin-converting enzyme 2 (ACE2) and the transmembrane protease, serine-subtype-2 (TMPRSS2) are important factors for SARS-CoV-2 infection. Clinical and pre-clinical studies demonstrated that RAAS-blocking agents can be safely used during a SARS-CoV-2 infection but it is unknown if DPP-4 inhibitors or SGLT2-blockers may promote COVID-19 by increasing the host viral entry enzymes ACE2 and TMPRSS2. Methods We investigated telmisartan, linagliptin and empagliflozin induced effects on renal and cardiac expression of ACE2, TMPRSS2 and key enzymes involved in RAAS (REN, AGTR2, AGT) under high-salt conditions in a non-diabetic experimental 5/6 nephrectomy (5/6 Nx) model. In the present study, the gene expression of Ace2, Tmprss2, Ren, Agtr2 and Agt was assessed with qRT-PCR and the protein expression of ACE2 and TMPRSS2 with immunohistochemistry in the following experimental groups: Sham + normal diet (ND) + placebo (PBO); 5/6Nx + ND + PBO; 5/6Nx + high salt-diet (HSD) + PBO; 5/6Nx + HSD + telmisartan; 5/6Nx + HSD + linagliptin; 5/6Nx + HSD + empagliflozin. Results In the kidney, the expression of Ace2 was not altered on mRNA level under disease and treatment conditions. The renal TMPRSS2 levels (mRNA and protein) were not affected, whereas the cardiac level was significantly increased in 5/6Nx rats. Intriguingly, the elevated TMPRSS2 protein expression in the heart was significantly normalized after treatment with telmisartan, linagliptin and empagliflozin. Conclusions Our study indicated that there is no upregulation regarding host factors potentially promoting SARS-CoV-2 virus entry into host cells when the SGLT2-blocker empagliflozin, telmisartan and the DPP4-inhibitor blocker linagliptin are used. The results obtained in a preclinical, experimental non-diabetic kidney failure model need confirmation in ongoing interventional clinical trials.
INTRODUCTION:
We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort.
METHODS:
We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI).
RESULTS:
Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI <= 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile.
DISCUSSION:
Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.