julilili42/papers huggingface dataset:
System f-omega with equirecursive types for datatype-generic programming
2016-01-07

Traversing an algebraic datatype by hand requires boilerplate code which duplicates the structure of the datatype. Datatype-generic programming (DGP) aims to eliminate such boilerplate code by decomposing algebraic datatypes into type constructor applications from which generic traversals can be synthesized. However, different traversals require different decompositions, which yield isomorphic but unequal types. This hinders the interoperability of different DGP techniques. In this paper, we propose Fωμ, an extension of the higher-order polymorphic lambda calculus Fω with records, variants, and equirecursive types. We prove the soundness of the type system, and show that type checking for first-order recursive types is decidable with a practical type checking algorithm. In our soundness proof we define type equality by interpreting types as infinitary λ-terms (in particular, Berarducci-trees). To decide type equality we β-normalize types, and then use an extension of equivalence checking for usual equirecursive types. Thanks to equirecursive types, new decompositions for a datatype can be added modularly and still interoperate with each other, allowing multiple DGP techniques to work together. We sketch how generic traversals can be synthesized, and apply these components to some examples. Since the set of datatype decomposition becomes extensible, System Fωμ enables using DGP techniques incrementally, instead of planning for them upfront or doing invasive refactoring.
Regional Gray Matter Volume Differences Between Adolescents With ADHD and Typically Developing Controls: Further Evidence for Anterior Cingulate Involvement
2016-01-08

Objective: The present study investigated structural brain differences between adolescents with ADHD and matched control participants. Method: Voxel-based morphometry (VBM) using the DARTEL approach was performed to assess regional gray matter (GM) volumes. Additionally, individual performance on tests of attention was recorded to correlate ADHD related cognitive impairments with regional gray matter abnormalities. Results: We found significantly smaller GM volume in subjects with ADHD compared to their matched controls within the anterior cingulate cortex (ACC), the occipital cortex, bilateral hippocampus/amygdala and in widespread cerebellar regions. Further, reductions of the ACC gray matter volume were found to correlate with scores of selective inattention. Conclusion: These findings underline that structural alterations in a widespread cortico-subcortical network seem to underlie the observable attention problems in patients with ADHD.
Quantumness of spin-1 states
2016-01-08

We investigate quantumness of spin-1 states, defined as the Hilbert-Schmidt\\ndistance to the convex hull of spin coherent states. We derive its analytic\\nexpression in the case of pure states as a function of the smallest eigenvalue\\nof the Bloch matrix and give explicitly the closest classical state for an\\narbitrary pure state. Numerical evidence is provided that the exact formula for\\npure states provides an upper bound on the quantumness of mixed states. Due to\\nthe connection between quantumness and entanglement we obtain new insights into\\nthe geometry of symmetric entangled states.\\n
Oxygen‐dependent regulation of c‐di‐ GMP synthesis by SadC controls alginate production in P seudomonas aeruginosa
2016-01-08

Summary P seudomonas aeruginosa produces increased levels of alginate in response to oxygen‐deprived conditions. The regulatory pathway(s) that links oxygen limitation to increased synthesis of alginate has remained elusive. In the present study, using immunofluorescence microscopy, we show that anaerobiosis‐induced alginate production by planktonic PAO 1 requires the diguanylate cyclase ( DGC ) SadC , previously identified as a regulator of surface‐associated lifestyles. Furthermore, we found that the gene products of PA 4330 and PA 4331, located in a predicted operon with sadC , have a major impact on alginate production: deletion of PA 4330 ( odaA , for oxygen‐dependent alginate synthesis activator) caused an alginate production defect under anaerobic conditions, whereas a PA 4331 ( odaI , for oxygen‐dependent alginate synthesis inhibitor) deletion mutant produced alginate also in the presence of oxygen, which would normally inhibit alginate synthesis. Based on their sequence, OdaA and OdaI have predicted hydratase and dioxygenase reductase activities, respectively. Enzymatic assays using purified protein showed that unlike OdaA , which did not significantly affect DGC activity of SadC , OdaI inhibited c‐di‐ GMP production by SadC . Our data indicate that SadC , OdaA and OdaI are components of a novel response pathway of P . aeruginosa that regulates alginate synthesis in an oxygen‐dependent manner.
Peregrine falcon egg pollutants: Mirror Stockholm POPs list including methylmercury
2016-01-08

The role of the peregrine falcon (Falco peregrinus) as a bioindicator for the accumulation of organohalogen compounds and other persistent organic pollutants has been established in field studies. Biometric indices for damage caused by pollutants such as the shell thickness and the shell index were determined and the egg contents were analyzed for various pollutants by gas chromatography/mass spectrometry. A wide range of chemically activated luciferase expression (CALUX®) bioassays were performed on subsamples of the eggs.The following organohalogen compounds were found in the eggs of 2009: dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethane, heptachlor epoxide, hexachlorobenzene, dieldrin, hexachlorocyclohexane, polychlorobiphenyls and polychlorodibenzodioxins and polychlorodibenzofurans, polybromodiphenyl ethers, hexabromocyclododecane, tetrabromobisphenyl A, perfluoro compounds, and mercury. The DDT metabolite, dichlorodiphenyldichloroethene (DDE) (11,800 ng/g dry matter),...
Effect of temporal resolution and serial autocorrelations in event‐related functional MRI
2016-01-09

Purpose To assess the impact of colored noise on statistics in event‐related functional MRI (fMRI) (visual stimulation using checkerboards) acquired by simultaneous multislice imaging enabling repetition times (TRs) between 2.64 to 0.26 s. Methods T‐values within the visual cortex obtained with analysis tools that assume a first‐order autoregressive plus white noise process (AR(1)+w) with a fixed AR coefficient versus higher‐order AR models with spatially varying AR coefficients were compared. In addition, dependency of T‐values on correction of physiological noise (respiration, heart rate) was evaluated. Results Optimal statistical power was obtained for a TR of 0.33 s, but T‐values as obtained by AR(1)+w models were strongly dependent on the predefined AR coefficients in fMRI with short TRs which required higher‐order AR models to achieve stable statistics. Direct estimation of AR coefficients revealed the highest values within the default mode network while physiological noise had little influence on statistics in cortical structures. Conclusion Colored noise in event‐related fMRI obtained at short TRs originates mainly from neural sources and calls for more sophisticated correction of serial autocorrelations which cannot be achieved with standard methods relying on AR(1)+w models with globally fixed AR coefficients. Magn Reson Med 76:1805–1813, 2016. © 2016 International Society for Magnetic Resonance in Medicine
Impact of refugee camps on their environment. A case study using multi-temporal SAR data
2016-01-10

Monitoring the environment is a key task of remote sensing in particular in areas whose access is difficult or dangerous or where dense cloud cover obscures optical information. This study proposes an assessment of landscape changes related to large refugee camps, where information about environmental conditions is needed by both humanitarian organizations and regional administrations. Our intention is to provide a robust workflow which is applicable for an operational use. The study area is located in Western Kenya hosts a total number of 350.000 people. Images of ERS-2 and Sentinel-1 are used for the assessment of land degradation in a semi-arid savannah between 1997 and 2014. We expect a relationship between the existence of the refugee camps and the degradation of surrounding landscapes. For this purpose we present an approach which objectively reveals developments in natural resources based on six land-use / land cover classes integrating their relative importance for the ecosystem given by expert-based weights.
Genetic Influence on the Peripheral Blood CD4+T-cell Differentiation Status in CMV Infection
2016-01-11

A latent infection with cytomegalovirus (CMV), a ubiquitous beta herpesvirus, is associated with an accumulation of late-differentiated memory T-cells, often accompanied by a reciprocal reduced frequency of early-differentiated cells (commonly also referred to as "naïve"). However, this impact of CMV on T-cell phenotypes is variable between individuals. Our previous findings in a subgroup of participants in the Leiden familial Longevity Study indicated an important role of genetics. For further testing, we have analyzed middle-aged monozygotic (MZ, n = 42) and dizygotic (DZ, n = 39) twin pairs from the Danish Twin Registry for their T-cell differentiation status, assessed by surface expression of CD27, CD28, CD57, and KLRG-1. We observed a significant intraclass correlation between cotwins of MZ, but not DZ pairs for the differentiation status of CD4<sup>+</sup> and CD8<sup>+</sup> subsets. Classical heritability analysis confirmed a substantial contribution of genetics to the differentiation status of T-cells in CMV infection. The humoral (IgG) response to different CMV antigens also seems to be genetically influenced, suggesting that a similar degree of immune control of the virus in MZ twins might be responsible for their similar T-cell differentiation status. Thus, the way T-cells differentiate in the face of a latent CMV infection, and the parallel humoral responses, both controlling the virus, are genetically influenced.
Within‐Person Link between Depressed Affect and Moderate‐to‐Vigorous Physical Activity in Adolescence: An Intensive Longitudinal Approach
2016-01-11

Background During adolescence, young women and men frequently show low physical activity and elevated depressed affect. This study aimed to examine the within‐person link between moderate‐to‐vigorous physical activity ( MVPA ) and depressed affect in everyday life. Methods Within an intensive longitudinal approach, adolescents ( N = 72; 37% young women; M age = 17.36 years; age range: 12–26 years; mid‐90% age range: 13–22 years) wore accelerometers to assess their daily MVPA and reported next‐morning and same‐evening depressed affect in diaries over eight consecutive days. The within‐person link between MVPA and depressed affect on the next morning (time‐lagged prediction) and the same evening (same‐day link) was analyzed with mixed‐effects models. Results More‐than‐usual MVPA significantly predicted less next‐morning depressed affect on weekdays in young women, to the extent that a 60‐min increase in MVPA over the person mean significantly predicted 50 per cent lower next‐morning depressed affect. Conclusions This study encourages the development of individually tailored physical activity interventions that could help adolescents enhance their daily amount of unstructured, self‐initiated MVPA to reduce depressed affect. This approach may be particularly suitable for young women who have the highest risk for an inactive lifestyle and elevated depressed affect.
Methods for the determination of the substantivity of topical formulations
2016-01-11

Skin diseases are usually treated using topical formulations. Frequently, multiple applications per day are necessary, as up to 90% of the formulation (and thus of the active) are withdrawn from the skin by contact with the environment. During the development of topical formulations ex vivo permeation and penetration experiments are deployed to characterize the formulations. Still, these tests do not take into account the removal of formulations during the application period. To date, only few methods exist to probe the substantivity of dermal formulations. The aim of this investigation was to develop methods that simulate skin-to-skin or clothing-to-skin contact and enable the determination of the amount of formulation that is removed from the skin due to the contact. Three different types of formulations were used to validate the systems: a conventional semisolid cream, an oil-in-oil-emulsion, and a film forming formulation. The results showed that the substantivity decreased in the order: film forming formulation > semisolid cream > oil-in-oil-emulsion. A similar trend could be determined with both methods although the total amounts of withdrawn formulation differed. The developed methods can add to the knowledge about the formulation and can be used to develop formulations that exhibit higher substantivity.
Ricci flows with bursts of unbounded curvature
2016-01-11

Given a completely arbitrary surface, whether or not it has bounded curvature, or even whether or not it is complete, there exists an instantaneously complete Ricci flow evolution of that surface that exists for a specific amount of time. In the case that the underlying Riemann surface supports a hyperbolic metric, this Ricci flow always exists for all time and converges (after scaling by a factor ) to this hyperbolic metric, i.e. our Ricci flow geometrises the surface. In this paper we show that there exist complete, bounded curvature initial metrics, including those conformal to a hyperbolic metric, which have subsequent Ricci flows developing unbounded curvature at certain intermediate times. In particular, when coupled with uniqueness, we find that any complete Ricci flow starting with such initial metrics must develop unbounded curvature over some intermediate time interval, but that nevertheless, the curvature must later become bounded and the flow must achieve geometrisation as t → ∞, even though there are other conformal deformations to hyperbolic metrics that do not involve unbounded curvature.Another consequence of our constructions is that while our Ricci flow must agree initially with the classical flow of Hamilton and Shi in the special case that the initial surface is complete and of bounded curvature, by uniqueness, it is now clear that our flow lasts for a longer time interval in general, with Shi's flow stopping when the curvature blows up, but our flow continuing strictly beyond in these situations.All our constructions of unbounded curvature developing and then disappearing are in two dimensions. Generalisations to higher dimensions are then immediate.
System f-omega with equirecursive types for datatype-generic programming
2016-01-11

Traversing an algebraic datatype by hand requires boilerplate code which duplicates the structure of the datatype. Datatype-generic programming (DGP) aims to eliminate such boilerplate code by decomposing algebraic datatypes into type constructor applications from which generic traversals can be synthesized. However, different traversals require different decompositions, which yield isomorphic but unequal types. This hinders the interoperability of different DGP techniques. In this paper, we propose Fωμ, an extension of the higher-order polymorphic lambda calculus Fω with records, variants, and equirecursive types. We prove the soundness of the type system, and show that type checking for first-order recursive types is decidable with a practical type checking algorithm. In our soundness proof we define type equality by interpreting types as infinitary λ-terms (in particular, Berarducci-trees). To decide type equality we β-normalize types, and then use an extension of equivalence checking for usual equirecursive types. Thanks to equirecursive types, new decompositions for a datatype can be added modularly and still interoperate with each other, allowing multiple DGP techniques to work together. We sketch how generic traversals can be synthesized, and apply these components to some examples. Since the set of datatype decomposition becomes extensible, System Fωμ enables using DGP techniques incrementally, instead of planning for them upfront or doing invasive refactoring.
Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG
2016-01-12

Abstract Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Experimental Design: Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control. Results: Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P = 0.010) or the 26-gene signature (P = 0.002). In multivariate analyses, in patients with HPV16 DNA–negative but not with HPV16 DNA–positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P = 0.006; 26-gene signature: HR 10.27, P = 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P = 0.016; SLC3A2: HR 8.54, P = 0.037; CD44: HR 3.36, P = 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA–negative subgroup. Conclusions: We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA–negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies. Clin Cancer Res; 22(11); 2639–49. ©2016 AACR.
Super-Resolution Microscopy Reveals Presynaptic Localization of the ALS/FTD Related Protein FUS in Hippocampal Neurons
2016-01-12

Fused in Sarcoma (FUS) is a multifunctional RNA-/DNA-binding protein, which is involved in the pathogenesis of the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A common hallmark of these disorders is the abnormal accumulation of mutated FUS protein in the cytoplasm. Under normal conditions FUS is confined to the nuclear compartment, in neurons, however, additional somatodendritic localization can be observed. In this study, we carefully analyzed the subcellular localization of endogenous FUS at synaptic sites of hippocampal neurons which are among the most affected cell types in FTD with FUS pathology. We could confirm a strong nuclear localization of FUS as well as its prominent and widespread neuronal expression throughout the adult and developing rat brain, particularly in the hippocampus, the cerebellum and the outer layers of the cortex. Intriguingly, FUS was also consistently observed at synaptic sites as detected by neuronal subcellular fractionation as well as by immunolabeling. To define a pre- and/or postsynaptic localization of FUS, we employed super-resolution fluorescence localization microscopy. FUS was found to be localized within the axon terminal in close proximity to the presynaptic vesicle protein Synaptophysin1 and adjacent to the active zone protein Bassoon, but well separated from the postsynaptic protein PSD-95. Having shown the presynaptic localization of FUS in the nervous system, a novel extranuclear role of FUS at neuronal contact sites has to be considered. Since there is growing evidence that local presynaptic translation might also be an important mechanism for plasticity, FUS - like the fragile X mental retardation protein FMRP - might act as one of the presynaptic RNA-binding proteins regulating this machinery. Our observation of presynaptic FUS should foster further investigations to determine its role in neurodegenerative diseases such as ALS and FTD.
Cellular and molecular modifier pathways in tauopathies: the big picture from screening invertebrate models
2016-01-12

Abstract Abnormal tau accumulations were observed and documented in post‐mortem brains of patients affected by Alzheimer's disease ( AD ) long before the identification of mutations in the Microtubule‐associated protein tau ( MAPT ) gene, encoding the tau protein, in a different neurodegenerative disease called Frontotemporal dementia and Parkinsonism linked to chromosome 17 ( FTDP ‐17). The discovery of mutations in the MAPT gene associated with FTDP ‐17 highlighted that dysfunctions in tau alone are sufficient to cause neurodegeneration. Invertebrate models have been diligently utilized in investigating tauopathies, contributing to the understanding of cellular and molecular pathways involved in disease etiology. An important discovery came with the demonstration that over‐expression of human tau in Drosophila leads to premature mortality and neuronal dysfunction including neurodegeneration, recapitulating some key neuropathological features of the human disease. The simplicity of handling invertebrate models combined with the availability of a diverse range of experimental resources make these models, in particular Drosophila a powerful invertebrate screening tool. Consequently, several large‐scale screens have been performed using Drosophila , to identify modifiers of tau toxicity. The screens have revealed not only common cellular and molecular pathways, but in some instances the same modifier has been independently identified in two or more screens suggesting a possible role for these modifiers in regulating tau toxicity. The purpose of this review is to discuss the genetic modifier screens on tauopathies performed in Drosophila and C. elegans models, and to highlight the common cellular and molecular pathways that have emerged from these studies. Here, we summarize results of tau toxicity screens providing mechanistic insights into pathological alterations in tauopathies. Key pathways or modifiers that have been identified are associated with a broad range of processes including, but not limited to, phosphorylation, cytoskeleton organization, axonal transport, regulation of cellular proteostasis, transcription, RNA metabolism, cell cycle regulation, and apoptosis. We discuss the utility and application of invertebrate models in elucidating the cellular and molecular functions of novel and uncharacterized disease modifiers identified in large‐scale screens as well as for investigating the function of genes identified as risk factors in genome‐wide association studies from human patients in the post‐genomic era. image In this review, we combined and summarized several large‐scale modifier screens performed in invertebrate models to identify modifiers of tau toxicity. A summary of the screens show that diverse cellular processes are implicated in the modification of tau toxicity. Kinases and phosphatases are the most predominant class of modifiers followed by components required for cellular proteostasis and axonal transport and cytoskeleton elements.