854 research outputs found

    Spin qubits with electrically gated polyoxometalate molecules

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    Spin qubits offer one of the most promising routes to the implementation of quantum computers. Very recent results in semiconductor quantum dots show that electrically-controlled gating schemes are particularly well-suited for the realization of a universal set of quantum logical gates. Scalability to a larger number of qubits, however, remains an issue for such semiconductor quantum dots. In contrast, a chemical bottom-up approach allows one to produce identical units in which localized spins represent the qubits. Molecular magnetism has produced a wide range of systems with tailored properties, but molecules permitting electrical gating have been lacking. Here we propose to use the polyoxometalate [PMo12O40(VO)2]q-, where two localized spins-1/2 can be coupled through the electrons of the central core. Via electrical manipulation of the molecular redox potential, the charge of the core can be changed. With this setup, two-qubit gates and qubit readout can be implemented.Comment: 9 pages, 6 figures, to appear in Nature Nanotechnolog

    Magnetic resonance imaging evidence for presymptomatic change in thalamus and caudate in familial Alzheimer’s disease

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    Amyloid imaging studies of presymptomatic familial Alzheimer’s disease have revealed the striatum and thalamus to be the earliest sites of amyloid deposition. This study aimed to investigate whether there are associated volume and diffusivity changes in these subcortical structures during the presymptomatic and symptomatic stages of familial Alzheimer’s disease. As the thalamus and striatum are involved in neural networks subserving complex cognitive and behavioural functions, we also examined the diffusion characteristics in connecting white matter tracts. A cohort of 20 presenilin 1 mutation carriers underwent volumetric and diffusion tensor magnetic resonance imaging, neuropsychological and clinical assessments; 10 were symptomatic, 10 were presymptomatic and on average 5.6 years younger than their expected age at onset; 20 healthy control subjects were also studied. We conducted region of interest analyses of volume and diffusivity changes in the thalamus, caudate, putamen and hippocampus and examined diffusion behaviour in the white matter tracts of interest (fornix, cingulum and corpus callosum). Voxel-based morphometry and tract-based spatial statistics were also used to provide unbiased whole-brain analyses of group differences in volume and diffusion indices, respectively. We found that reduced volumes of the left thalamus and bilateral caudate were evident at a presymptomatic stage, together with increased fractional anisotropy of bilateral thalamus and left caudate. Although no significant hippocampal volume loss was evident presymptomatically, reduced mean diffusivity was observed in the right hippocampus and reduced mean and axial diffusivity in the right cingulum. In contrast, symptomatic mutation carriers showed increased mean, axial and in particular radial diffusivity, with reduced fractional anisotropy, in all of the white matter tracts of interest. The symptomatic group also showed atrophy and increased mean diffusivity in all of the subcortical grey matter regions of interest, with increased fractional anisotropy in bilateral putamen. We propose that axonal injury may be an early event in presymptomatic Alzheimer’s disease, causing an initial fall in axial and mean diffusivity, which then increases with loss of axonal density. The selective degeneration of long-coursing white matter tracts, with relative preservation of short interneurons, may account for the increase in fractional anisotropy that is seen in the thalamus and caudate presymptomatically. It may be owing to their dense connectivity that imaging changes are seen first in the thalamus and striatum, which then progress to involve other regions in a vulnerable neuronal network

    Smc5/6: a link between DNA repair and unidirectional replication?

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    Of the three structural maintenance of chromosome (SMC) complexes, two directly regulate chromosome dynamics. The third, Smc5/6, functions mainly in homologous recombination and in completing DNA replication. The literature suggests that Smc5/6 coordinates DNA repair, in part through post-translational modification of uncharacterized target proteins that can dictate their subcellular localization, and that Smc5/6 also functions to establish DNA-damage-dependent cohesion. A nucleolar-specific Smc5/6 function has been proposed because Smc5/6 yeast mutants display penetrant phenotypes of ribosomal DNA (rDNA) instability. rDNA repeats are replicated unidirectionally. Here, we propose that unidirectional replication, combined with global Smc5/6 functions, can explain the apparent rDNA specificity

    Using florbetapir positron emission tomography to explore cerebrospinal fluid cut points and gray zones in small sample sizes

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    INTRODUCTION: We aimed to assess the feasibility of determining Alzheimer's disease cerebrospinal fluid (CSF) cut points in small samples through comparison with amyloid positron emission tomography (PET). METHODS: Twenty-three individuals (19 patients, four controls) had CSF measures of amyloid beta (Aβ)1-42 and total tau/Aβ1-42 ratio, and florbetapir PET. We compared CSF measures with visual and quantitative (standardized uptake value ratio [SUVR]) PET measures of amyloid. RESULTS: Seventeen of 23 were amyloid-positive on visual reads, and 14 of 23 at an SUVR of ≥1.1. There was concordance (positive/negative on both measures) in 20 of 23, of whom 19 of 20 were correctly classified at an Aβ1-42 of 630 ng/L, and 20 of 20 on tau/Aβ1-42 ratio (positive ≥0.88; negative ≤0.34). Three discordant cases had Aβ1-42 levels between 403 and 729 ng/L and tau/Aβ1-42 ratios of 0.54-0.58. DISCUSSION: Comparing amyloid PET and CSF biomarkers provides a means of assessing CSF cut points in vivo, and can be applied to small sample sizes. CSF tau/Aβ1-42 ratio appears robust at predicting amyloid status, although there are gray zones where there remains diagnostic uncertainty

    Spin dynamics of molecular nanomagnets fully unraveled by four-dimensional inelastic neutron scattering

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    Molecular nanomagnets are among the first examples of spin systems of finite size and have been test-beds for addressing a range of elusive but important phenomena in quantum dynamics. In fact, for short-enough timescales the spin wavefunctions evolve coherently according to the an appropriate cluster spin-Hamiltonian, whose structure can be tailored at the synthetic level to meet specific requirements. Unfortunately, to this point it has been impossible to determine the spin dynamics directly. If the molecule is sufficiently simple, the spin motion can be indirectly assessed by an approximate model Hamiltonian fitted to experimental measurements of various types. Here we show that recently-developed instrumentation yields the four-dimensional inelastic-neutron scattering function S(Q,E) in vast portions of reciprocal space and enables the spin dynamics to be determined with no need of any model Hamiltonian. We exploit the Cr8 antiferromagnetic ring as a benchmark to demonstrate the potential of this new approach. For the first time we extract a model-free picture of the quantum dynamics of a molecular nanomagnet. This allows us, for example, to examine how a quantum fluctuation propagates along the ring and to directly test the degree of validity of the N\'{e}el-vector-tunneling description of the spin dynamics

    Consensus over Random Graph Processes: Network Borel-Cantelli Lemmas for Almost Sure Convergence

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    Distributed consensus computation over random graph processes is considered. The random graph process is defined as a sequence of random variables which take values from the set of all possible digraphs over the node set. At each time step, every node updates its state based on a Bernoulli trial, independent in time and among different nodes: either averaging among the neighbor set generated by the random graph, or sticking with its current state. Connectivity-independence and arc-independence are introduced to capture the fundamental influence of the random graphs on the consensus convergence. Necessary and/or sufficient conditions are presented on the success probabilities of the Bernoulli trials for the network to reach a global almost sure consensus, with some sharp threshold established revealing a consensus zero-one law. Convergence rates are established by lower and upper bounds of the ϵ\epsilon-computation time. We also generalize the concepts of connectivity/arc independence to their analogues from the ∗*-mixing point of view, so that our results apply to a very wide class of graphical models, including the majority of random graph models in the literature, e.g., Erd\H{o}s-R\'{e}nyi, gossiping, and Markovian random graphs. We show that under ∗*-mixing, our convergence analysis continues to hold and the corresponding almost sure consensus conditions are established. Finally, we further investigate almost sure finite-time convergence of random gossiping algorithms, and prove that the Bernoulli trials play a key role in ensuring finite-time convergence. These results add to the understanding of the interplay between random graphs, random computations, and convergence probability for distributed information processing.Comment: IEEE Transactions on Information Theory, In Pres

    Statistical Power of Model Selection Strategies for Genome-Wide Association Studies

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    Genome-wide association studies (GWAS) aim to identify genetic variants related to diseases by examining the associations between phenotypes and hundreds of thousands of genotyped markers. Because many genes are potentially involved in common diseases and a large number of markers are analyzed, it is crucial to devise an effective strategy to identify truly associated variants that have individual and/or interactive effects, while controlling false positives at the desired level. Although a number of model selection methods have been proposed in the literature, including marginal search, exhaustive search, and forward search, their relative performance has only been evaluated through limited simulations due to the lack of an analytical approach to calculating the power of these methods. This article develops a novel statistical approach for power calculation, derives accurate formulas for the power of different model selection strategies, and then uses the formulas to evaluate and compare these strategies in genetic model spaces. In contrast to previous studies, our theoretical framework allows for random genotypes, correlations among test statistics, and a false-positive control based on GWAS practice. After the accuracy of our analytical results is validated through simulations, they are utilized to systematically evaluate and compare the performance of these strategies in a wide class of genetic models. For a specific genetic model, our results clearly reveal how different factors, such as effect size, allele frequency, and interaction, jointly affect the statistical power of each strategy. An example is provided for the application of our approach to empirical research. The statistical approach used in our derivations is general and can be employed to address the model selection problems in other random predictor settings. We have developed an R package markerSearchPower to implement our formulas, which can be downloaded from the Comprehensive R Archive Network (CRAN) or http://bioinformatics.med.yale.edu/group/

    Cellular Radiosensitivity: How much better do we understand it?

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    Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

    Wild Chimpanzees Exchange Meat for Sex on a Long-Term Basis

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    Humans and chimpanzees are unusual among primates in that they frequently perform group hunts of mammalian prey and share meat with conspecifics. Especially interesting are cases in which males give meat to unrelated females. The meat-for-sex hypothesis aims at explaining these cases by proposing that males and females exchange meat for sex, which would result in males increasing their mating success and females increasing their caloric intake without suffering the energetic costs and potential risk of injury related to hunting. Although chimpanzees have been shown to share meat extensively with females, there has not been much direct evidence in this species to support the meat-for-sex hypothesis. Here we show that female wild chimpanzees copulate more frequently with those males who, over a period of 22 months, share meat with them. We excluded other alternative hypotheses to exchanging meat for sex, by statistically controlling for rank of the male, age, rank and gregariousness of the female, association patterns of each male-female dyad and meat begging frequency of each female. Although males were more likely to share meat with estrous than anestrous females given their proportional representation in hunting parties, the relationship between mating success and sharing meat remained significant after excluding from the analysis sharing episodes with estrous females. These results strongly suggest that wild chimpanzees exchange meat for sex, and do so on a long-term basis. Similar studies on humans will determine if the direct nutritional benefits that women receive from hunters in foraging societies could also be driving the relationship between reproductive success and good hunting skills
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