Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Myelin in Theiler's Virus Persistence in the Central Nervous System

Theiler's virus, a picornavirus, persists for life in the central nervous system of mouse and causes a demyelinating disease that is a model for multiple sclerosis. The virus infects neurons first but persists in white matter glial cells, mainly oligodendrocytes and macrophages. The mechanism, by which the virus traffics from neurons to glial cells, and the respective roles of oligodendrocytes and macrophages in persistence are poorly understood. We took advantage of our previous finding that the shiverer mouse, a mutant with a deletion in the myelin basic protein gene (Mbp), is resistant to persistent infection to examine the role of myelin in persistence. Using immune chimeras, we show that resistance is not mediated by immune responses or by an efficient recruitment of inflammatory cells into the central nervous system. With both in vivo and in vitro experiments, we show that the mutation does not impair the permissiveness of neurons, oligodendrocytes, and macrophages to the virus. We demonstrate that viral antigens are present in cytoplasmic channels of myelin during persistent infection of wild-type mice. Using the optic nerve as a model, we show that the virus traffics from the axons of retinal ganglion cells to the cytoplasmic channels of myelin, and that this traffic is impaired by the shiverer mutation. These results uncover an unsuspected axon to myelin traffic of Theiler's virus and the essential role played by the infection of myelin/oligodendrocyte in persistence.
IDEAL in 2014 illustrates interaction networks composed of intrinsically disordered proteins and their binding partners

IDEAL (Intrinsically Disordered proteins with Extensive Annotations and Literature, http://www.ideal.force.cs.is.nagoya-u.ac.jp/IDEAL/) is a collection of intrinsically disordered proteins (IDPs) that cannot adopt stable globular structures under physiological conditions. Since its previous publication in 2012, the number of entries in IDEAL has almost tripled (120 to 340). In addition to the increase in quantity, the quality of IDEAL has been significantly improved. The new IDEAL incorporates the interactions of IDPs and their binding partners more explicitly, and illustrates the protein–protein interaction (PPI) networks and the structures of protein complexes. Redundant experimental data are arranged based on the clustering of Protein Data Bank entries, and similar sequences with the same binding mode are grouped. As a result, the new IDEAL presents more concise and informative experimental data. Nuclear magnetic resonance (NMR) disorder is annotated in a systematic manner, by identifying the regions with large deviations among the NMR models. The ordered/disordered and new domain predictions by DICHOT are available, as well as the domain assignments by HMMER. Some examples of the PPI networks and the highly deviated regions derived from NMR models will be described, together with other advances. These enhancements will facilitate deeper understanding of IDPs, in terms of their flexibility, plasticity and promiscuity.
The effects of visual input on postural control mechanisms: an analysis of center-of-pressure trajectories using the auto-regressive model.

New measures to characterize center-of-pressure (COP) trajectories during quiet standing were proposed and then utilized to investigate changes in postural control with respect to visual input. Eleven healthy male subjects (aged 20-27 years) were included in this study. An instrumented force platform was used to measure the time-varying displacements of the COP under each subject's feet during quiet standing. The subjects were tested under eyes-open and eyes-closed conditions. The COP time series were separately analyzed for the medio-lateral and antero-posterior directions. The proposed measures were obtained from the parameter estimation of auto-regressive (AR) models. The percentage contributions and geometrical moment of AR coefficients showed statistically significant differences between vision conditions. The present COP displacements under the eyes-open condition showed higher correlation with the past COP displacements at longer lag times, when compared to the eyes-closed condition. In contrast, no significant differences between vision conditions were found for conventional summary statistics, e.g., the total length of the COP path. These results suggest that the AR parameters are useful for the evaluation of postural stability and balance function, even for healthy young individuals. The role of visual input in the postural control system and implications of the findings were discussed.
How to Elicit Many Probabilities

In building Bayesian belief networks, the elicitation of all probabilities required can be a major obstacle. We learned the extent of this often-cited observation in the construction of the probabilistic part of a complex influence diagram in the field of cancer treatment. Based upon our negative experiences with existing methods, we designed a new method for probability elicitation from domain experts. The method combines various ideas, among which are the ideas of transcribing probabilities and of using a scale with both numerical and verbal anchors for marking assessments. In the construction of the probabilistic part of our influence diagram, the method proved to allow for the elicitation of many probabilities in little time.
Highly conserved upstream regions of the alpha 1-antitrypsin gene in two mouse species govern liver-specific expression by different mechanisms

alpha 1-Antitrypsin (AT), the major elastase inhibitor in mammalian serum, is produced primarily in the liver. We have characterized AT gene structure and expression in the mouse species Mus caroli, which expresses high levels of AT in the kidneys as well as in the liver. Analysis of cDNA and genomic clones showed that the AT gene in M. caroli exhibits high sequence homology (greater than 90%) to the gene in laboratory mice (M. domesticus) throughout the coding and 5'-flanking regions. Despite this extensive sequence conservation, the functional organization of cis-acting regulatory elements governing liver-specific expression is strikingly different between these species. Transient-transfection assays showed that the proximal region of the M. caroli promoter (i.e., between -120 and -2 relative to the transcriptional start site) is 10-fold more active than the analogous region of M. domesticus in driving the expression of an indicator gene in cultured liver cells. The increased activity of the proximal region of the M. caroli AT promoter appears to be the result of one or both of the two base substitutions at positions -46 and -48. The weak proximal promoter in M. domesticus is compensated for by the presence of upstream, liver-specific enhancers between -199 and -520; the analogous region in M. caroli is inactive. Thus, during the course of evolution, the modest 7% sequence divergence that has occurred between the 5'-flanking regions of the AT genes in these two species has generated distinct, yet equally effective, modes of hepatocyte-specific expression.
A neural network approach to the placement problem

In this paper, we introduce a new neural network approach to the placement of gate array designs. The network used is a Kohonen self-organising map. An abstract specification of the design is converted to a set of appropriate input vectors fed to the network at random. At the end of the process, the map shows a 2-dimensional plane of the design in which the modules with higher connectivity are placed adjacent to each other, hence minimising total connection length in the design. The approach can consider external connections and is able to place modules in a rectilinear boundary. These features makes the approach capable of being used in hierarchical floorplanning algorithms.
The Mammalian Target of Rapamycin Signaling Pathway: Twists and Turns in the Road to Cancer Therapy

The immunosuppressive drug rapamycin played a key role in the functional characterization of mammalian target of rapamycin (mTOR), an unusual protein kinase that coordinates growth factor and nutrient availability with cell growth and proliferation. Several rapamycin-related compounds are now in various stages of clinical development as anticancer agents. This article highlights recent advances in our understanding of the mTOR signaling pathway and the implications of these findings for the clinical application of mTOR inhibitors in cancer patients.
“He's a Big Old Girl!” Negotiation by Gender Inversion in Gay Men's Speech

ABSTRACT On the basis of participant observation in the gay communities of San Francisco, Paris and Oslo, this article charts a pattern of gender inversion in the negotiation of identities and social relations that can be related to an international gay culture. The use of gender inversion in gay men's speech is seen as evidence of the discursive construction of specific generic identities whose capacity to carry meaning is dependent on conventional categories of gender.
Experimental Shopping Analysis of Consumer Stimulation and Motivational States in Shopping Experiences

The present research investigates the roles of both the individual reaction to environmental stimuli and personality characteristics in consumers’ pursuit of hedonic and/or utilitarian shopping values. The individual reaction to environmental stimuli is operationalised by two closely related measures: the optimal stimulation level (OSL), concerning the level of external stimulation with which an individual feels comfortable, and the arousability, concerning the rate with which the internal stimulation (i.e. the arousal) level of an individual changes in response to a sudden increase (or decrease) in the environmental stimulation. Results from an experimental study showed, first, that these two constructs (OSL and arousability) are positively correlated with those personality traits (i.e. Agreeableness and Openness to Experience, according to the Big Five-Factor mode (see Digman 1990)) mostly associated with the hedonic shopping value. Second, drawing on Reversal Theory (see Apter 1989), results showed that paratelic individuals (i.e. those who are interested in the shopping activity itself) have higher OSL and arousability than telic individuals (those who are interested in shopping outcomes, such as the purchase of specific products). These motivational states, in turn, are differently related to the two shopping values (i.e. hedonic vs utilitarian). Theoretical and practical implications for marketing are discussed.
Early Microglia Activation Precedes Photoreceptor Degeneration in a Mouse Model of CNGB1-Linked Retinitis Pigmentosa

Retinitis pigmentosa (RP) denotes a family of inherited blinding eye diseases characterized by progressive degeneration of rod and cone photoreceptors in the retina. In most cases, a rod-specific genetic defect results in early functional loss and degeneration of rods, which is followed by degeneration of cones and loss of daylight vision at later stages. Microglial cells, the immune cells of the central nervous system, are activated in retinas of RP patients and in several RP mouse models. However, it is still a matter of debate whether activated microglial cells may be responsible for the amplification of the typical degenerative processes. Here, we used Cngb1−/− mice, which represent a slow degenerative mouse model of RP, to investigate the extent of microglia activation in retinal degeneration. With a combination of FACS analysis, immunohistochemistry and gene expression analysis we established that microglia in the Cngb1−/− retina were already activated in an early, predegenerative stage of the disease. The evidence available so far suggests that early retinal microglia activation represents a first step in RP, which might initiate or accelerate photoreceptor degeneration.
Maternal Situations: Sectarianism and Civility in a Divided City

This paper explores the tensions between civility and sectarianism in contemporary Belfast. Drawing on interviews with mothers engaged in raising young children in the largely working-class and divided inner city, the paper offers a situated account of the dynamics of social reproduction and change. This is pursued through an analysis of the interplay between expectations of civility and sectarianism in three situations: walking, shopping and playing. The tensions and dilemmas of maternal action as the divided inner city is navigated indicate the gendered character of civility, an important emerging norm facilitating social change in the post-conflict era. The situation of motherhood itself, both at the centre of ethno-national reproduction and at the interface of public and private life, is not insignificant in routinely drawing mothers into the everyday dynamics of post-conflict continuity and change.
Commentary: Functional connectome fingerprint: identifying individuals using patterns of brain connectivity

Centre of Mathematics, Computation and Cognition, Universidade Federal do ABC, Santo Andre, Brazil, Department of Radiology, School of Medicine, University of São Paulo, São Paulo, Brazil, Hospital de Clinicas de Porto Alegre and Department of Psychiatry, Federal University of Rio Grande do Sul, Porto Alegre, Brazil, National Institute of Developmental Psychiatry for Children and Adolescents, CNPq, São Paulo, Brazil, 5 Interdisciplinary Lab for Clinical Neurosciences, Universidade Federal de São Paulo, São Paulo, Brazil, Department of Psychiatry, School of Medicine, University of São
Homework: Motivation and Learning Preference

A Model of Homework Performance and Instrument Validation Understanding Homework Profiling Homework Motivation and Preference Research on Homework Motivation and Preference Preferred versus Actual and Parental Awareness of Homework Performance Cultural, Gender, and Age Difference in Homework Motivation and Preference Relationship of Homework Motivation and Preference to Achievement and Attitude toward Homework Homework Motivation and Preference of Gifted and Talented Learners Homework Strategies and Interventions Solving Homework Problems Homework Intervention: Focusing on Homework Motivation and Preference Children's Structural and Motivational Needs in Homework Arranging Home Environment Epilogue Bibliography Index
Pharmacokinetic-Pharmacodynamic Modeling the Hypnotic Effect of Sevoflurane Using the Spectral Entropy of the Electroencephalogram

Spectral entropy is a new electroencephalogram (EEG)-derived parameter that may be used to model the pharmacokinetic-pharmacodynamic (PKPD) effects of general anesthetics. In the present study we sought to derive a PKPD model of the relationship between sevoflurane concentration and spectral entropy of the EEG. We collected spectral entropy data during increasing and decreasing sevoflurane anesthesia from 20 patients. The first cycle consisted of induction and lightening phases with no supplemental medications. An effect-site compartment and inhibitory Emax model described the relation between sevoflurane concentration and spectral entropy. PKPD parameters were derived from the full cycle and separately from the increasing and decreasing stages. The second anesthetic cycle consisted of a redeepening phase only and included airway manipulation and routinely administered adjunctives. PKPD data obtained from the first cycle were used to predict second cycle entropy changes. There was a consistent relationship between effect-site sevoflurane concentration and spectral entropy (median absolute weighted residual = 11.6%). For complete first-cycle response entropy (mean ± sd): T1/2 Keo = 2.4 ± 1.5 min, &ggr; = 5.9 ± 2.3, EC50 = 1.7 ± 0.3. We found significant differences between &ggr; values when the sevoflurane concentration was increasing (61.1 ± 55.2) compared with the decreasing part of the cycle (5.7 ± 2.8). Above an effect-site concentration of 3%, spectral entropy of the EEG is unresponsive to further increases in sevoflurane concentration. The effect-compartment inhibitory Emax model accurately describes the relation between sevoflurane concentration and spectral entropy of the EEG. Spectral entropy decreases with increasing sevoflurane concentrations up to 3%. The steepness of the dose-response curve varies between phases of increasing and decreasing anesthetic concentrations.
Characterization of Treatment Resistant Depression Episodes in a Cohort of Patients from a US Commercial Claims Database

Context Treatment Resistant Depression (TRD) is a significant and burdensome health concern. Objective To characterize, compare and understand the difference between TRD and non-TRD patients and episodes in respect of their episode duration, treatment patterns and healthcare resource utilization. Design and Setting Patients between 18 and 64 years with a new diagnosis of major depressive disorder (MDD) and without a previous or comorbid diagnosis of schizophrenia or bipolar disease were included from PharMetrics Integrated Database, a claims database of commercial insurers in the US. Episodes of these patients in which there were at least two distinct failed regimens involving antidepressants and antipsychotics were classified as TRD. Patients 82,742 MDD patients were included in the analysis; of these patients, 125,172 episodes were identified (47,654 of these were drug-treated episodes). Main Outcome Measures Comparison between TRD and non-TRD episodes in terms of their duration, number and duration of lines of treatment, comorbidities, and medical resource utilization. Results Of the treated episodes, 6.6% (N = 3,134) met the criteria for TRD. The median time to an episode becoming TRD was approximately one year. The mean duration of a TRD episode was 1,004 days (vs. 452 days for a non-TRD episode). More than 75% of TRD episodes had at least four lines of therapy; half of the treatment regimens included a combination of drugs. Average hospitalization costs were higher for TRD than non-TRD episodes: $6,464 vs. $1,734, as were all other health care utilization costs. Conclusions While this study was limited to relatively young and commercially covered patients, used a rigorous definition of TRD and did not analyze for cause or consequence, the results highlight high unmet medical need and burden of TRD on patients and health care resources.
DWI Intensity Values Predict FLAIR Lesions in Acute Ischemic Stroke

Background and Purpose In acute stroke, the DWI-FLAIR mismatch allows for the allocation of patients to the thrombolysis window (<4.5 hours). FLAIR-lesions, however, may be challenging to assess. In comparison, DWI may be a useful bio-marker owing to high lesion contrast. We investigated the performance of a relative DWI signal intensity (rSI) threshold to predict the presence of FLAIR-lesions in acute stroke and analyzed its association with time-from-stroke-onset. Methods In a retrospective, dual-center MR-imaging study we included patients with acute stroke and time-from-stroke-onset ≤12 hours (group A: n = 49, 1.5T; group B: n = 48, 3T). DW- and FLAIR-images were coregistered. The largest lesion extent in DWI defined the slice for further analysis. FLAIR-lesions were identified by 3 raters, delineated as regions-of-interest (ROIs) and copied on the DW-images. Circular ROIs were placed within the DWI-lesion and labeled according to the FLAIR-pattern (FLAIR+ or FLAIR−). ROI-values were normalized to the unaffected hemisphere. Adjusted and nonadjusted receiver-operating-characteristics (ROC) curve analysis on patient level was performed to analyze the ability of a DWI- and ADC-rSI threshold to predict the presence of FLAIR-lesions. Spearman correlation and adjusted linear regression analysis was performed to assess the relationship between DWI-intensity and time-from-stroke-onset. Results DWI-rSI performed well in predicting lesions in FLAIR-imaging (mean area under the curve (AUC): group A: 0.84; group B: 0.85). An optimal mean DWI-rSI threshold was identified (A: 162%; B: 161%). ADC-maps performed worse (mean AUC: A: 0.58; B: 0.77). Adjusted regression models confirmed the superior performance of DWI-rSI. Correlation coefficents and linear regression showed a good association with time-from-stroke-onset for DWI-rSI, but not for ADC-rSI. Conclusion An easily assessable DWI-rSI threshold identifies the presence of lesions in FLAIR-imaging with good accuracy and is associated with time-from-stroke-onset in acute stroke. This finding underlines the potential of a DWI-rSI threshold as a marker of lesion age.
Serum Vitamin D status and its relations to body fatness and fitness and risk factors in young adults

The study examined the relations of serum vitamin D levels to body fatness, cardiorespiratory fitness (CRF), and metabolic risk factors in young adults in Korea. A total of 593 young men completed a health examination, body fatness, maximal treadmill exercise test, and assessment of metabolic risk factors. Participants were classified by serum vitamin D levels as deficient (< 20 ng/mL), insufficient (20~30 ng/mL), and sufficient (> 30 ng/mL). Body fatness, CRF, and metabolic risk factors were evaluated according to serum vitamin D classification. Significant inverse trends in body fatness and metabolic risk factors were observed, as was a significant linear trend for CRF across incremental vitamin D categories in this study population. Serum vitamin D levels were negatively associated with body fatness parameters, blood pressures, total cholesterol, triglycerides, and insulin and positively associated with high-density lipoprotein cholesterol and CRF. Compared to the BMI-based lean group, the obese groups had significantly higher odds ratio for serum vitamin D insufficiency before and after adjusting for age, CRF, and physical activity. Similarly, compared to percent body fat- and waist circumference-based lean groups, the obese groups had significant higher odds ratios for serum vitamin D insufficiency. In conclusion, the current findings of the study suggest that along with vitamin D intakes, body fat loss and outdoor physical activity should be promoted as non-pharmacologic means to improve metabolic risk factors in young adults.
An Analysis of the Search Spaces for Generate and Validate Patch Generation Systems

We present the first systematic analysis of key characteristics of patch search spaces for automatic patch generation systems. We analyze sixteen different configurations of the patch search spaces of SPR and Prophet, two cur- rent state-of-the-art patch generation systems. The analysis shows that 1) correct patches are sparse in the search spaces (typically at most one correct patch per search space per defect), 2) incorrect patches that nevertheless pass all of the test cases in the validation test suite are typically orders of magnitude more abundant, and 3) leveraging information other than the test suite is therefore critical for enabling the system to successfully isolate correct patches.We also characterize a key tradeoff in the structure of the search spaces. Larger and richer search spaces that contain correct patches for more defects can actually cause systems to find fewer, not more, correct patches. We identify two reasons for this phenomenon: 1) increased validation times because of the presence of more candidate patches and 2) more incorrect patches that pass the test suite and block the discovery of correct patches. These fundamental properties, which are all characterized for the first time in this paper, help explain why past systems often fail to generate correct patches and help identify challenges, opportunities, and productive future directions for the field.
Lives in Translation: Sikh Youth as British Citizens

1 Introduction: A Different Immigration Story 2 From Subjects to Citizens 3 The Politics of Language Recognition 4 "Becoming like Us" 5 Mediated Traditions 6 "You Can't Be Religious and Be Westernized" 7 "There's a Time to Act English and a Time to Act Indian" 8 Consciousness, Self-Awareness, and the Life Path Epilogue: An Unfinished Story Notes Works Cited Index Acknowledgments