Miracle-dz/UniFAR-FTUs huggingface dataset:
The Synaptic Proteome during Development and Plasticity of the Mouse Visual Cortex*

During brain development, the neocortex shows periods of enhanced plasticity, which enables the acquisition of knowledge and skills that we use and build on in adult life. Key to persistent modifications of neuronal connectivity and plasticity of the neocortex are molecular changes occurring at the synapse. Here we used isobaric tag for relative and absolute quantification to measure levels of 467 synaptic proteins in a well-established model of plasticity in the mouse visual cortex and the regulation of its critical period. We found that inducing visual cortex plasticity by monocular deprivation during the critical period increased levels of kinases and proteins regulating the actin-cytoskeleton and endocytosis. Upon closure of the critical period with age, proteins associated with transmitter vesicle release and the tubulin- and septin-cytoskeletons increased, whereas actin-regulators decreased in line with augmented synapse stability and efficacy. Maintaining the visual cortex in a plastic state by dark rearing mice into adulthood only partially prevented these changes and increased levels of G-proteins and protein kinase A subunits. This suggests that in contrast to the general belief, dark rearing does not simply delay cortical development but may activate signaling pathways that specifically maintain or increase the plasticity potential of the visual cortex. Altogether, this study identified many novel candidate plasticity proteins and signaling pathways that mediate synaptic plasticity during critical developmental periods or restrict it in adulthood.
Structure of the Children's Revised Impact of Event Scale (CRIES) with Children and Adolescents Exposed to Debris Flood

Aim PTSD symptoms were pervasive among children and adolescents after experiencing or exposure to traumatic events. Screening and diagnosis of PTSD symptoms is crucial in trauma-related research and practice. The 13-item Children's Revised Impact of Event Scale (CRIES) has been demonstrated to be a valid and reliable tool to achieve this goal. This study was designed to examine the psychometric properties of the 13-item CRIES in a sample of Chinese debris flood victims. Methods A total of 268 participants (145 girls, 123 boys) aged 8–18 years were recruited from an integral part of a service oriented project, supported by the Institute of Psychology, Chinese Academy of Sciences following the debris flood. The participants were given the 13-item CRIES 3 months after the debris flood. Results The results of confirmatory factor analysis indicated that a two-factor structure (intrusion+arousal vs avoidance) emerged as the model best fit in total sample, boys and girls subsamples, respectively. The scale was also demonstrated to have good internal consistency (Cronbach's alpha = 0.83). Conclusion The study confirmed the good psychometric properties of the CRIES and its' applicability to Chinese children and adolescents. Moreover, these findings imply that the CRIES factor structure is stable across age, gender, and different types of trauma.
Methylene Blue Modulates β-Secretase, Reverses Cerebral Amyloidosis, and Improves Cognition in Transgenic Mice*

Background: Recent focus has been given to anti-amyloidogenic approaches for Alzheimer disease therapy. Results: Methylene blue prevented behavioral impairment and mitigated Alzheimer disease-like pathology. Conclusion: Methylene blue may be prophylactic for Alzheimer disease by inhibiting β-secretase activity and mitigating brain pathology. Significance: Oral methylene blue treatment modulates β-secretase. Amyloid precursor protein (APP) proteolysis is required for production of amyloid-β (Aβ) peptides that comprise β-amyloid plaques in the brains of patients with Alzheimer disease (AD). Here, we tested whether the experimental agent methylene blue (MB), used for treatment of methemoglobinemia, might improve AD-like pathology and behavioral deficits. We orally administered MB to the aged transgenic PSAPP mouse model of cerebral amyloidosis and evaluated cognitive function and cerebral amyloid pathology. Beginning at 15 months of age, animals were gavaged with MB (3 mg/kg) or vehicle once daily for 3 months. MB treatment significantly prevented transgene-associated behavioral impairment, including hyperactivity, decreased object recognition, and defective spatial working and reference memory, but it did not alter nontransgenic mouse behavior. Moreover, brain parenchymal and cerebral vascular β-amyloid deposits as well as levels of various Aβ species, including oligomers, were mitigated in MB-treated PSAPP mice. These effects occurred with inhibition of amyloidogenic APP proteolysis. Specifically, β-carboxyl-terminal APP fragment and β-site APP cleaving enzyme 1 protein expression and activity were attenuated. Additionally, treatment of Chinese hamster ovary cells overexpressing human wild-type APP with MB significantly decreased Aβ production and amyloidogenic APP proteolysis. These results underscore the potential for oral MB treatment against AD-related cerebral amyloidosis by modulating the amyloidogenic pathway.
Epidemiologic Features of Kawasaki Disease in South Korea: Data from Nationwide Survey, 2009–2011

Background: To assess the recent epidemiologic features of Kawasaki disease (KD) in South Korea from the nationwide survey conducted between 2009 and 2011. Methods: We collected data regarding the incidence, symptoms, treatment and coronary complications associated with acute KD by sending questionnaires to the 100 hospitals that have pediatric residency programs from 2009 to 2011. Results: We received complete responses from 73 hospitals and partial responses from 14 hospitals. A total of 13,031 patients of KD were reported from the 87 hospitals (3941 in 2009, 4635 in 2010 and 4455 in 2011). The male to female ratio was 1.44:1, and the median age at diagnosis was 28 months. From the questionnaires with complete responses, we noted that the incidence of KD per 100,000 children <5 years of age was 115.4 in 2009, 132.9 in 2010 and 134.4 in 2011 (average rate, 127.7). KD occurred more frequently during summer (June, July and August) and during winter (December and January). The recurrence rate was 3.83%. The standard dose of intravenous immunoglobulin was administered to 93.6% of the patients, and nonresponder rate was 11.6%. Coronary aneurysm occurred in 1.9% of the patients and giant aneurysm developed in 26 patients (0.26%) over 3 years, and 2 patients had myocardial infarction. No mortality was reported. Conclusions: The average annual incidence of KD in South Korea has continuously increased to 134.4 per 100,000 children <5 years of age in 2011, which is the second highest incidence of KD worldwide, following its incidence in Japan.
Skin aging and hair graying in Hiroshima.

Estimation of age by appearance, skin elasticity and looseness, and hair graying were studied in the irradiated and nonirradiated population of Hiroshima. No differences in these several measurements were detected between the radiation- exposed and nonexposed components of the sample. The study provided no support for the concept of a general, nonspecific aging acceleration, exemplified by aging of skin and hair, as a late radiation sequela. (auth)
Indirect Immunofluorescence Assay for the Simultaneous Detection of Antibodies against Clinically Important Old and New World Hantaviruses

In order to detect serum antibodies against clinically important Old and New World hantaviruses simultaneously, multiparametric indirect immunofluorescence assays (IFAs) based on biochip mosaics were developed. Each of the mosaic substrates consisted of cells infected with one of the virus types Hantaan (HTNV), Puumala (PUUV), Seoul (SEOV), Saaremaa (SAAV), Dobrava (DOBV), Sin Nombre (SNV) or Andes (ANDV). For assay evaluation, serum IgG and IgM antibodies were analyzed using 184 laboratory-confirmed hantavirus-positive sera collected at six diagnostic centers from patients actively or previously infected with the following hantavirus serotypes: PUUV (Finland, n = 97); SEOV (China, n = 5); DOBV (Romania, n = 7); SNV (Canada, n = 23); ANDV (Argentina and Chile, n = 52). The control panel comprised 89 sera from healthy blood donors. According to the reference tests, all 184 patient samples were seropositive for hantavirus-specific IgG (n = 177; 96%) and/or IgM (n = 131; 72%), while all control samples were tested negative. In the multiparametric IFA applied in this study, 183 (99%) of the patient sera were IgG and 131 (71%) IgM positive (accordance with the reference tests: IgG, 96%; IgM, 93%). Overall IFA sensitivity for combined IgG and IgM analysis amounted to 100% for all serotypes, except for SNV (96%). Of the 89 control sera, 2 (2%) showed IgG reactivity against the HTNV substrate, but not against any other hantavirus. Due to the high cross-reactivity of hantaviral nucleocapsid proteins, endpoint titrations were conducted, allowing serotype determination in >90% of PUUV- and ANDV-infected patients. Thus, multiparametric IFA enables highly sensitive and specific serological diagnosis of hantavirus infections and can be used to differentiate PUUV and ANDV infection from infections with Murinae-borne hantaviruses (e.g. DOBV and SEOV).
Stabilization Strategies for Unstable Dynamics

Background When humans are faced with an unstable task, two different stabilization mechanisms are possible: a high-stiffness strategy, based on the inherent elastic properties of muscles/tools/manipulated objects, or a low-stiffness strategy, based on an explicit positional feedback mechanism. Specific constraints related to the dynamics of the task and/or the neuromuscular system often force people to adopt one of these two strategies. Methodology/Findings This experiment was designed such that subjects could achieve stability using either strategy, with a marked difference in terms of effort and control requirements between the two strategies. The task was to balance a virtual mass in an unstable environment via two elastic linkages that connected the mass to each hand. The dynamics of the mass under the influence of the unstable force field and the forces applied through the linkages were simulated using a bimanual, planar robot. The two linkages were non-linear, with a stiffness that increased with the amount of stretch. The mass could be stabilized by stretching the linkages to achieve a stiffness that was greater than the instability coefficient of the unstable field (high-stiffness), or by balancing the mass with sequences of small force impulses (low-stiffness). The results showed that 62% of the subjects quickly adopted the high-stiffness strategy, with stiffness ellipses that were aligned along the direction of instability. The remaining subjects applied the low-stiffness strategy, with no clear preference for the orientation of the stiffness ellipse. Conclusions The choice of a strategy was based on the bimanual coordination of the hands: high-stiffness subjects achieved stability quickly by separating the hands to stretch the linkages, while the low-stiffness subjects kept the hands close together and took longer to achieve stability but with lower effort. We suggest that the existence of multiple solutions leads to different types of skilled behavior in unstable environments.
Comparison of immunohistochemistry, DNA sequencing and allele-specific PCR for the detection of IDH1 mutations in gliomas.

Previous studies have identified mutations of the isocitrate dehydrogenase 1 (IDH1) gene in more than 70% of World Health Organization (WHO) grade II and III gliomas. The most frequent mutation leads to a specific amino acid change from arginine to histidine at codon 132 (c.395G>A, p.R132H). IDH1 mutated tumors have a better prognosis than IDH1 non-mutated tumors. The aim of our study was to evaluate and compare the methods of mIDH1 R132H immunohistochemistry, allele-specific PCR and DNA sequencing for determination of IDH1 status. We performed a retrospective study of 91 patients with WHO grade II (n=43) and III (n=48) oligodendrogliomas. A fragment of exon 4 spanning the sequence encoding the catalytic domain of IDH1, including codon 132, was amplified and sequenced using standard conditions. Allele-specific amplification was performed using two forward primers with variations in their 3' nucleotides such that each was specific for the wild-type or the mutated variant, and one reverse primer. Immunohistochemistry was performed with mouse monoclonal mIDH1 R132H. DNA was extracted from FFPE sections following macrodissection. IDH1 mutations were found in 55/90 patients (61.1%) by direct sequencing. R132H mutations were found in 47/55 patients (85.4%). The results of the allele-specific PCR positively correlated with those from DNA sequencing. Other mutations (p.R132C, p.R132S and pR132G) were found by DNA sequencing in 3, 3 and 2 tumors, respectively (8/55 patients, 14.6%). mIDH1 R132H immunostaining was found in the 47 patients presenting the R132H mutation (sensitivity 47/47, 100% for this mutation). None of the tumors presenting a wild-type IDH1 gene were stained (specificity 35/35, 100%). Our results demonstrate that immunohistochemistry using the mIDH1 R132H antibody and allele-specific amplification are highly sensitive techniques to detect the most frequent mutation of the IDH1 gene.
Introductory Remarks on Large Deviation Statistics

The physical concept of entropy as it is used in thermodynamics is related to the mathematical formulation of a Shannon entropy. Usually only the Shannon entropy of equilibrium distributions such as a canonical distribution is considered. Large deviations statistics goes beyond that framework. Entropies are considered for arbitrary distributions or physical states, and they describe, e.g., “how fast” non-equilibrium distributions and states “die out” with increasing number of degrees of freedom or increasing number of particles. Hence the concept of an entropy acquires a new meaning, referring to the statistical fluctuations in collectives of empirical events. In the particular case of experiments with independent and identically distributed (i.i.d.) events, Shannon entropy can be shown to play its usual role (Sanov’s theorem). Jaynes’ maximum entropy principle, important in statistical physics, is a consequence of Sanov’s theorem and thereby obtains a precise interpretation. In the general case of non-i.i. d. events, all sorts of (even nonconvex) entropies can arise. As illustrative examples, large deviation statistics of phase transitions and multifractals are addressed.
Income inequality, individual income, and mortality in Danish adults: analysis of pooled data from two cohort studies

Abstract Objective: To analyse the association between area income inequality and mortality after adjustment for individual income and other established risk factors. Design: Analysis of pooled data from two cohort studies. The relation between income inequality in small areas of residence (parishes) and individual mortality was examined with Cox proportional hazard analyses. Setting: Two population studies conducted in Copenhagen, Denmark. Participants: 13 710 women and 12 018 men followed for a mean of 12.8 years. Main outcome measure: All cause mortality. Results: Age standardised mortality was highest in the parishes with the least equal income distribution. After adjustment for individual risk factors, parish income inequality was not associated with mortality, whereas individual household income was. Thus, individuals in the highest income quarter had lower mortality than those in the lowest quarter (adjusted hazard ratio for men 0.51 (95% confidence interval 0.45 to 0.59) and for women 0.60 (0.54 to 0.68)). Conclusion: Area income inequality is not in itself associated with all cause mortality in this Danish population. Adjustment for individual risk factors makes the apparent effect disappear. This may be the result of Denmark's welfare system, based on a Nordic model. What is already known on this topic Several ecological studies have shown that higher levels of income inequality in countries, states, or smaller areas are associated with higher all cause mortality A few prospective studies from the United States have examined this after controlling for individual risk factors What this study adds Inequality in the distribution of income in parishes in Copenhagen is as high as inequality reported from metropolitan areas in the United States Area based income inequality did not affect all cause mortality after adjustment for individual income and other risk factors Denmark's welfare system (based on a Nordic model) may even out the effect of area inequality
Epidemiology of acute rheumatic fever in New Zealand 1996–2005

Aim: Acute rheumatic fever (ARF) and its sequela chronic rheumatic heart disease remain significant causes of morbidity and mortality in New Zealand, particularly among Māori and Pacific peoples. Despite its importance, ARF epidemiology has not been reviewed recently. The aims of this study were to assess trends in ARF incidence rates between 1996 and 2005 and the extent to which ARF is concentrated in certain populations based on age, sex, ethnicity and geographical location.
Inactivation of the peroxisomal ABCD2 transporter in the mouse leads to late-onset ataxia involving mitochondria, Golgi and endoplasmic reticulum damage.

ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substances, ranging from peptides to lipids, across cell or organelle membranes. In peroxisomes, a subfamily of four ABC transporters (ABCD1 to ABCD4) has been related to fatty acid transport, because patients with mutations in ABCD1 (ALD gene) suffer from X-linked adrenoleukodystrophy (X-ALD), a disease characterized by an accumulation of very-long-chain fatty acids (VLCFAs). Inactivation in the mouse of the abcd1 gene leads to a late-onset neurodegenerative condition, comparable to the late-onset form of X-ALD [Pujol, A. , Hindelang, C. , Callizot, N. , Bartsch, U. , Schachner, M. and Mandel, J.L. (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet. , 11, 499-505. ]. In the present work, we have generated and characterized a mouse deficient for abcd2, the closest paralog to abcd1. The main pathological feature in abcd2-/- mice is a late-onset cerebellar and sensory ataxia, with loss of cerebellar Purkinje cells and dorsal root ganglia cell degeneration, correlating with accumulation of VLCFAs in the latter cellular population. Axonal degeneration was present in dorsal and ventral columns in spinal cord. We have identified mitochondrial, Golgi and endoplasmic reticulum damage as the underlying pathological mechanism, thus providing evidence of a disturbed organelle cross-talk, which may be at the origin of the pathological cascade.
Learning from the past: answering new questions with past answers

Community-based Question Answering sites, such as Yahoo! Answers or Baidu Zhidao, allow users to get answers to complex, detailed and personal questions from other users. However, since answering a question depends on the ability and willingness of users to address the asker's needs, a significant fraction of the questions remain unanswered. We measured that in Yahoo! Answers, this fraction represents 15% of all incoming English questions. At the same time, we discovered that around 25% of questions in certain categories are recurrent, at least at the question-title level, over a period of one year. We attempt to reduce the rate of unanswered questions in Yahoo! Answers by reusing the large repository of past resolved questions, openly available on the site. More specifically, we estimate the probability whether certain new questions can be satisfactorily answered by a best answer from the past, using a statistical model specifically trained for this task. We leverage concepts and methods from query-performance prediction and natural language processing in order to extract a wide range of features for our model. The key challenge here is to achieve a level of quality similar to the one provided by the best human answerers. We evaluated our algorithm on offline data extracted from Yahoo! Answers, but more interestingly, also on online data by using three "live" answering robots that automatically provide past answers to new questions when a certain degree of confidence is reached. We report the success rate of these robots in three active Yahoo! Answers categories in terms of both accuracy, coverage and askers' satisfaction. This work presents a first attempt, to the best of our knowledge, of automatic question answering to questions of social nature, by reusing past answers of high quality.
Opsin Repertoire and Expression Patterns in Horseshoe Crabs: Evidence from the Genome of Limulus polyphemus (Arthropoda: Chelicerata)

Horseshoe crabs are xiphosuran chelicerates, the sister group to arachnids. As such, they are important for understanding the most recent common ancestor of Euchelicerata and the evolution and diversification of Arthropoda. Limulus polyphemus is the most investigated of the four extant species of horseshoe crabs, and the structure and function of its visual system have long been a major focus of studies critical for understanding the evolution of visual systems in arthropods. Likewise, studies of genes encoding Limulus opsins, the protein component of the visual pigments, are critical for understanding opsin evolution and diversification among chelicerates, where knowledge of opsins is limited, and more broadly among arthropods. In the present study, we sequenced and assembled a high quality nuclear genomic sequence of L. polyphemus and used these data to annotate the full repertoire of Limulus opsins. We conducted a detailed phylogenetic analysis of Limulus opsins, including using gene structure and synteny information to identify relationships among different opsin classes. We used our phylogeny to identify significant genomic events that shaped opsin evolution and therefore the visual system of Limulus. We also describe the tissue expression patterns of the 18 opsins identified and show that transcripts encoding a number, including a peropsin, are present throughout the central nervous system. In addition to significantly extending our understanding of photosensitivity in Limulus and providing critical insight into the genomic evolution of horseshoe crab opsins, this work provides a valuable genomic resource for addressing myriad questions related to xiphosuran physiology and arthropod evolution.
Reasoning about Record Matching Rules

To accurately match records it is often necessary to utilize the semantics of the data. Functional dependencies (FDs) have proven useful in identifying tuples in a clean relation, based on the semantics of the data. For all the reasons that FDs and their inference are needed, it is also important to develop dependencies and their reasoning techniques for matching tuples from unreliable data sources. This paper investigates dependencies and their reasoning for record matching. (a) We introduce a class of matching dependencies (MDs) for specifying the semantics of data in unreliable relations, defined in terms of similarity metrics and a dynamic semantics. (b) We identify a special case of MDs, referred to as relative candidate keys (RCKs), to determine what attributes to compare and how to compare them when matching records across possibly different relations. (c) We propose a mechanism for inferring MDs, a departure from traditional implication analysis, such that when we cannot match records by comparing attributes that contain errors, we may still find matches by using other, more reliable attributes. (d) We provide an O(n2) time algorithm for inferring MDs, and an effective algorithm for deducing a set of RCKs from MDs. (e) We experimentally verify that the algorithms help matching tools efficiently identify keys at compile time for matching, blocking or windowing, and that the techniques effectively improve both the quality and efficiency of various record matching methods.