Time-varying correlation coefficients estimation and its application to dynamic connectivity analysis of fMRI

Exploration of the dynamics of functional brain connectivity based on the correlation coefficients of functional magnetic resonance imaging (fMRI) data is important for understanding the brain mechanisms. Because fMRI data are time-varying in nature, the functional connectivity shows substantial fluctuations and dynamic characteristics. However, an effective method for estimating time-varying functional connectivity is lacking, which is mainly due to the difficulty in choosing an appropriate window to localize the time-varying correlation coefficients (TVCC). This paper introduces a novel method for adaptively estimating the TVCC of non-stationary signals and studies its application to infer dynamic functional connectivity of fMRI data in a visual task. The proposed method employs a sliding window having a certain bandwidth to estimate the TVCC locally and the window bandwidths are selected adaptively by a local plug-in rule to minimize the mean squared error. The results show that the functional connectivity changes in the visual task are transient, which suggests that simply assuming sustained connectivity changes during task period might not be sufficient to capture dynamic connectivity changes induced by tasks.published_or_final_versio

Lightest sterile neutrino abundance within the nuMSM

We determine the abundance of the lightest (dark matter) sterile neutrinos created in the Early Universe due to active-sterile neutrino transitions from the thermal plasma. Our starting point is the field-theoretic formula for the sterile neutrino production rate, derived in our previous work [JHEP 06(2006)053], which allows to systematically incorporate all relevant effects, and also to analyse various hadronic uncertainties. Our numerical results differ moderately from previous computations in the literature, and lead to an absolute upper bound on the mixing angles of the dark matter sterile neutrino. Comparing this bound with existing astrophysical X-ray constraints, we find that the Dodelson-Widrow scenario, which proposes sterile neutrinos generated by active-sterile neutrino transitions to be the sole source of dark matter, is only possible for sterile neutrino masses lighter than 3.5 keV (6 keV if all hadronic uncertainties are pushed in one direction and the most stringent X-ray bounds are relaxed by a factor of two). This upper bound may conflict with a lower bound from structure formation, but a definitive conclusion necessitates numerical simulations with the non-equilibrium momentum distribution function that we derive. If other production mechanisms are also operative, no upper bound on the sterile neutrino mass can be established.Comment: 34 pages. v2: clarifications and a reference added; published version. v3: erratum appende

A semi-parametric approach to estimate risk functions associated with multi-dimensional exposure profiles: application to smoking and lung cancer

A common characteristic of environmental epidemiology is the multi-dimensional aspect of exposure patterns, frequently reduced to a cumulative exposure for simplicity of analysis. By adopting a flexible Bayesian clustering approach, we explore the risk function linking exposure history to disease. This approach is applied here to study the relationship between different smoking characteristics and lung cancer in the framework of a population based case control study

B-L Cosmic Strings in Heterotic Standard Models

E_{8} X E_{8} heterotic string and M-theory, when compactified on smooth Calabi-Yau manifolds with SU(4) vector bundles, can give rise to softly broken N=1 supersymmetric theories with the exact matter spectrum of the MSSM, including three right-handed neutrinos and one Higgs-Higgs conjugate pair of supermultiplets. These vacua have the SU(3)_{C} X SU(2)_{L} X U(1)_{Y} gauge group of the standard model augmented by an additional gauged U(1)_{B-L}. Their minimal content requires that the B-L symmetry be spontaneously broken by a vacuum expectation value of at least one right-handed sneutrino. The soft supersymmetry breaking operators can induce radiative breaking of the B-L gauge symmetry with an acceptable B-L/electroweak hierarchy. In this paper, it is shown that U(1)_{B-L} cosmic strings occur in this context, potentially with both bosonic and fermionic superconductivity. We present a numerical analysis that demonstrates that boson condensates can, in principle, form for theories of this type. However, the weak Yukawa and gauge couplings of the right-handed sneutrino suggests that bosonic superconductivity will not occur in the simplest vacua in this context. The electroweak phase transition also disallows fermion superconductivity, although substantial bound state fermion currents can exist.Comment: 41 pages, 5 figure

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Release of Lungworm Larvae from Snails in the Environment: Potential for Alternative Transmission Pathways

Background: Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis). In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host. Methodology/Principal Findings: Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior) and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior). Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior. Conclusions: Results of this study indicate that A. abstrusus and T. brevior infective L3 are shed in the mucus of H. aspersa or in water where infected gastropods had died submerged. Both elimination pathways may represent alternative route(s) of environmental contamination and source of the infection for these nematodes under field conditions and may significantly affect the epidemiology of feline lungworms. Considering that snails may act as intermediate hosts for other metastrongyloid species, the environmental contamination by mucus-released larvae is discussed in a broader context

Fat Mass and Obesity-Associated Gene (FTO) in Eating Disorders: Evidence for Association of the rs9939609 Obesity Risk Allele with Bulimia nervosa and Anorexia nervosa

Objective: The common single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity-associated gene (FTO) is associated with obesity. As genetic variants associated with weight regulation might also be implicated in the etiology of eating disorders, we evaluated whether SNP rs9939609 is associated with bulimia nervosa (BN) and anorexia nervosa (AN). Methods: Association of rs9939609 with BN and AN was assessed in 689 patients with AN, 477 patients with BN, 984 healthy non-population-based controls, and 3,951 population-based controls (KORA-S4). Based on the familial and premorbid occurrence of obesity in patients with BN, we hypothesized an association of the obesity risk A-allele with BN. Results: In accordance with our hypothesis, we observed evidence for association of the rs9939609 A-allele with BN when compared to the non-population-based controls (unadjusted odds ratio (OR) = 1.142, one-sided 95% confidence interval (CI) 1.001-infinity; one-sided p = 0.049) and a trend in the population-based controls (OR = 1.124, one-sided 95% CI 0.932-infinity; one-sided p = 0.056). Interestingly, compared to both control groups, we further detected a nominal association of the rs9939609 A-allele to AN (OR = 1.181, 95% CI 1.027-1.359, two-sided p = 0.020 or OR = 1.673, 95% CI 1.101-2.541, two-sided p = 0.015,). Conclusion: Our data suggest that the obesity-predisposing FTO allele might be relevant in both AN and BN. Copyright (C) 2012 S. Karger GmbH, Freibur

Monoidal computer III: A coalgebraic view of computability and complexity

Monoidal computer is a categorical model of intensional computation, where many different programs correspond to the same input-output behavior. The upshot of yet another model of computation is that a categorical formalism should provide a much needed high level language for theory of computation, flexible enough to allow abstracting away the low level implementation details when they are irrelevant, or taking them into account when they are genuinely needed. A salient feature of the approach through monoidal categories is the formal graphical language of string diagrams, which supports visual reasoning about programs and computations. In the present paper, we provide a coalgebraic characterization of monoidal computer. It turns out that the availability of interpreters and specializers, that make a monoidal category into a monoidal computer, is equivalent with the existence of a *universal state space*, that carries a weakly final state machine for any pair of input and output types. Being able to program state machines in monoidal computers allows us to represent Turing machines, to capture their execution, count their steps, as well as, e.g., the memory cells that they use. The coalgebraic view of monoidal computer thus provides a convenient diagrammatic language for studying computability and complexity.Comment: 34 pages, 24 figures; in this version: added the Appendi

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer