Miracle-dz/UniFAR-FTUs huggingface dataset:
Atomic structure of a toxic, oligomeric segment of SOD1 linked to amyotrophic lateral sclerosis (ALS)

Significance More than 170 mutations in superoxide dismutase 1 (SOD1) are linked to inherited forms of ALS, and aggregates of this protein are a pathological feature associated with this disease. Although it is accepted that SOD1 gains a toxic function in the disease state, a molecular understanding of the toxic species is lacking. Here, we identify a short segment of SOD1 that is both necessary and sufficient for toxicity to motor neurons. The crystal structure of the segment reveals an out-of-register β-sheet oligomer, providing a structural rationale for the toxic effects of mutant SOD1 in ALS. Fibrils and oligomers are the aggregated protein agents of neuronal dysfunction in ALS diseases. Whereas we now know much about fibril architecture, atomic structures of disease-related oligomers have eluded determination. Here, we determine the corkscrew-like structure of a cytotoxic segment of superoxide dismutase 1 (SOD1) in its oligomeric state. Mutations that prevent formation of this structure eliminate cytotoxicity of the segment in isolation as well as cytotoxicity of the ALS-linked mutants of SOD1 in primary motor neurons and in a Danio rerio (zebrafish) model of ALS. Cytotoxicity assays suggest that toxicity is a property of soluble oligomers, and not large insoluble aggregates. Our work adds to evidence that the toxic oligomeric entities in protein aggregation diseases contain antiparallel, out-of-register β-sheet structures and identifies a target for structure-based therapeutics in ALS.
Lattice Defects in Hydrogenated and HPT Processed Pd

Pure palladium (99.95%) was hydrogenated, subsequently deformed by High Pressure Torsion (HPT) and analyzed by differential scanning calorimetry (DSC). For comparison some hydrogen-free HPT processed samples were also investigated. In case of the hydrogenated HPT Pd, the concentration of single / double vacancies is noticeably higher. The importance of hydrogen for the formation and stabilization of vacancy type defects and dislocations is discussed.
Intraspecific Variation in Cryptocaryon irritans

ABSTRACT. Intraspecific variation in the ciliate Cryptocaryon irritans was examined using sequences of the first internal transcribed spacer region (ITS‐1) of ribosomal DNA (rDNA) combined with developmental and morphological characters. Amplified rDNA sequences consisting of 151 bases of the flanking 18 S and 5.8 S regions, and the entire ITS‐1 region (169 or 170 bases), were determined and compared for 16 isolates of C. irritans from Australia, Israela and the USA. There was one variable base between isolates in the 18 S region nd 11 variables indicate that Australian C. irritans isolates from estuarine (Moreton Bay) and coral reef (Heron Island) environments are distinct. The Heron Island isolate was genetically closer to morphologically dissimilar isolates from Israel (1.8% divergence) and USA (2.3 % divergence) than it was to the Moreton Bay isolates. Three isolates maintained in our laboratory since February 1994 originated from the same source. During this time the sequence of the isolates from wild fish in Moreton Bay remained unchanged. These genetic differences indicate the existence of a founder effects in laboratorty populations of C. irritans. The genetic variation found here, combined with known morphological and developmental differences, is used to characterise four strains of C. irritans.
Controlled Exposure of Healthy Young Volunteers to Ozone Causes Cardiovascular Effects

Background— Recent epidemiology studies have reported associations between short-term ozone exposure and mortality. Such studies have previously reported associations between airborne particulate matter pollution and mortality, and support for a causal relationship has come from controlled-exposure studies that describe pathophysiological mechanisms by which particulate matter could induce acute mortality. In contrast, for ozone, almost no controlled-human-exposure studies have tested whether ozone exposure can modulate the cardiovascular system. Methods and Results— Twenty-three young healthy individuals were exposed in a randomized crossover fashion to clean air and to 0.3-ppm ozone for 2 hours while intermittently exercising. Blood was obtained immediately before exposure, immediately afterward, and the next morning. Continuous Holter monitoring began immediately before exposure and continued for 24 hours. Lung function was performed immediately before and immediately after exposure, and bronchoalveolar lavage was performed 24 hours after exposure. Immediately after ozone exposure, we observed a 98.9% increase in interleukin-8, a 21.4% decrease in plasminogen activator inhibitor-1, a 51.3% decrease in the high-frequency component of heart rate variability, and a 1.2% increase in QT duration. Changes in interleukin-1B and plasminogen activator inhibitor-1 were apparent 24 hours after exposure. In agreement with previous studies, we also observed ozone-induced drops in lung function and an increase in pulmonary inflammation. Conclusions— This controlled-human-exposure study shows that ozone can cause an increase in vascular markers of inflammation and changes in markers of fibrinolysis and markers that affect autonomic control of heart rate and repolarization. We believe that these findings provide biological plausibility for the epidemiology studies that associate ozone exposure with mortality. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT01492517.
Detection of Glottal Closure Instants From Speech Signals: A Quantitative Review

The pseudo-periodicity of voiced speech can be exploited in several speech processing applications. This requires however that the precise locations of the glottal closure instants (GCIs) are available. The focus of this paper is the evaluation of automatic methods for the detection of GCIs directly from the speech waveform. Five state-of-the-art GCI detection algorithms are compared using six different databases with contemporaneous electroglottographic recordings as ground truth, and containing many hours of speech by multiple speakers. The five techniques compared are the Hilbert Envelope-based detection (HE), the Zero Frequency Resonator-based method (ZFR), the Dynamic Programming Phase Slope Algorithm (DYPSA), the Speech Event Detection using the Residual Excitation And a Mean-based Signal (SEDREAMS) and the Yet Another GCI Algorithm (YAGA). The efficacy of these methods is first evaluated on clean speech, both in terms of reliabililty and accuracy. Their robustness to additive noise and to reverberation is also assessed. A further contribution of the paper is the evaluation of their performance on a concrete application of speech processing: the causal-anticausal decomposition of speech. It is shown that for clean speech, SEDREAMS and YAGA are the best performing techniques, both in terms of identification rate and accuracy. ZFR and SEDREAMS also show a superior robustness to additive noise and reverberation.
Semantic Role Labeling using Maximum Entropy Model

In this paper, we propose a semantic role labeling method using a maximum entropy model, which enables not only to exploit rich features but also to alleviate the data sparseness problem in a well-founded model. For applying the maximum entropy model to semantic role labeling, we take a incremental approach as follows: firstly, the semantic roles are assigned to the arguments in the immediate clause including a predicate, and then, the semantic roles are assigned to the arguments in the upper clauses by using previously assigned labels. The experimental result shows that the proposed method has about 64.76% (F1-measure) on the test set.
Onecut transcription factors act upstream of Isl1 to regulate spinal motoneuron diversification

During development, spinal motoneurons (MNs) diversify into a variety of subtypes that are specifically dedicated to the motor control of particular sets of skeletal muscles or visceral organs. MN diversification depends on the coordinated action of several transcriptional regulators including the LIM-HD factor Isl1, which is crucial for MN survival and fate determination. However, how these regulators cooperate to establish each MN subtype remains poorly understood. Here, using phenotypic analyses of single or compound mutant mouse embryos combined with gain-of-function experiments in chick embryonic spinal cord, we demonstrate that the transcriptional activators of the Onecut family critically regulate MN subtype diversification during spinal cord development. We provide evidence that Onecut factors directly stimulate Isl1 expression in specific MN subtypes and are therefore required to maintain Isl1 production at the time of MN diversification. In the absence of Onecut factors, we observed major alterations in MN fate decision characterized by the conversion of somatic to visceral MNs at the thoracic levels of the spinal cord and of medial to lateral MNs in the motor columns that innervate the limbs. Furthermore, we identify Sip1 (Zeb2) as a novel developmental regulator of visceral MN differentiation. Taken together, these data elucidate a comprehensive model wherein Onecut factors control multiple aspects of MN subtype diversification. They also shed light on the late roles of Isl1 in MN fate decision.
Finite Field Multiplier Using Redundant Representation

This article presents simple and highly regular architectures for finite field multipliers using a redundant representation. The basic idea is to embed a finite field into a cyclotomic ring which is based on the elegant multiplicative structure of a cyclic group. One important feature of our architectures is that they provide area-time trade-offs which enable us to implement the multipliers in a partial-parallel/hybrid fashion. This hybrid architecture has great significance in its VLSI implementation in very large fields. The squaring operation using the redundant representation is simply a permutation of the coordinates. It is shown that, when there is an optimal normal basis, the proposed bit-serial and hybrid multiplier architectures have very low space complexity. Constant multiplication is also considered and is shown to have an advantage in using the redundant representation.
SOX9 is a key player in ultraviolet B-induced melanocyte differentiation and pigmentation

SOX (SRY type HMG box) proteins are transcription factors that are predominantly known for their roles during development. During melanocyte development from the neural crest, SOX10 regulates microphthalmia-associated transcription factor, which controls a set of genes critical for pigment cell development and pigmentation, including dopachrome tautomerase and tyrosinase. We report here that another SOX factor, SOX9, is expressed by melanocytes in neonatal and adult human skin and is up-regulated by UVB exposure. We demonstrate that this regulation is mediated by cAMP and protein kinase. We also show that agouti signal protein, a secreted factor known to decrease pigmentation, down-regulates SOX9 expression. In adult and neonatal melanocytes, SOX9 regulates microphthalmia-associated transcription factor, dopachrome tautomerase, and tyrosinase promoters, leading to an increase in the expression of these key melanogenic proteins and finally to a stimulation of pigmentation. SOX9 completes the complex and tightly regulated process leading to the production of melanin by acting at a very upstream level. This role of SOX9 in pigmentation emphasizes the poorly understood impact of SOX proteins in adult tissues.
Fenugreek Seed Extract Inhibit Fat Accumulation and Ameliorates Dyslipidemia in High Fat Diet-Induced Obese Rats

This study investigated the inhibitory effect of aqueous extract of Trigonella foenum-graecum seeds (AqE-TFG) on fat accumulation and dyslipidemia in high fat diet- (HFD-) induced obese rats. Female Wistar rats were fed with HFD ad libitum, and the rats on HFD were treated orally with AqE-TFG or orlistat ((HFD for 28 days + AqE-TFG (0.5 and 1.0 g/kg) or orlistat (10 mg/kg) from day 8 to 28), respectively. Treatment with AqE-TFG produced significant reduction in body weight gain, body mass index (BMI), white adipose tissue (WAT) weights, blood glucose, serum insulin, lipids, leptin, lipase, and apolipoprotein-B levels and elevation in adiponectin levels. AqE-TFG improved serum aspartate amino transferase (AST), alanine amino transferase (ALT), and lactate dehydrogenase (LDH) levels. AqE-TFG treatment reduced the hepatic and cardiac thiobarbituric acid reactive substances (TBARS) and elevated the antioxidant enzyme (glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) levels. In addition, liver and uterine WAT lipogenic enzyme (fatty acid synthetase (FAS) and glucose-6-phosphate dehydrogenase (G6PD)) activities were restored towards normal levels. These findings demonstrated the preventive effect of AqE-TFG on fat accumulation and dyslipidemia, due to inhibition of impaired lipid digestion and absorption, in addition to improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, increased antioxidant defense, and downregulation of lipogenic enzymes.
Prevalence of Campylobacter jejuni in two California chicken processing plants

Two federally inspected California chicken processing plants participated in Campylobacter jejuni prevalence studies. Twelve sampling sites were included in each of four groups. Groups were based on bird age, scald water temperature, and plant sampled. Scald water temperatures of 60 degrees C (140 degrees F) did not contribute to a lower prevalence of C. jejuni in edible parts, as did temperatures of 53 degrees C (127 degrees F) and 49 degrees C (120 degrees F). The feather picker and chilling tank were areas of major cross-contamination. C. jejuni was isolated from 68% of the ready-for-market products. The organism was recovered from 60 to 100% of the ceca in the four groups, and some numbers in the fecal material exceeded 10(6)/g. The level of C. jejuni in intestinal tracts seemed to correlate with the presence of the organism in the edible parts.
Disk galaxy evolution up to redshift z=1 ∗

We have performed intermediate-resolution VLT/FORS spectroscopy and HST/ACS imaging of 129 field spiral galaxies within the FORS Deep Field. The gala xies cover the redshift range 0.1 ≤ z ≤ 1.0 and comprise all types from Sa to Sdm/Im. Spatially resolved rotation curves were extracted and fitted with synthetic velocity fields that take into account all geometric (e.g., inclination and misalignment) and observational effects (in particular, blurring due to optical beam smearing and seeing). Using these fits, the maximum rotation velocity Vmax could be determined for 73 objects. The Tully-Fisher relation of this sample at a mean look-back time of ∼ 5 Gyr shows a luminosity evolution which amounts to ∼ 2 mag in rest-frame B for low-mass spirals (Vmax ≈ 100 km/s) but is negligible for high-mass spirals (Vmax ≈ 300 km/s). This confirms our previous analysis which was limited to ground-based imaging. The observed overluminosity of low-mass galaxies is at variance with predictions from simulations. On the other hand, at given Vmax, we find slightly smaller disk sizes towards higher redshifts, in compliance with the CDM hierarchical model. The observed mass-dependent luminosity evolution might therefore point towards the need for a more realistic modelling of the stellar (i.e. baryonic) compone nt in N-body codes.
miRNA regulation of BK polyomavirus replication during early infection

Viral microRNAs (miRNAs) play an important role during infection by posttranscriptionally regulating both host and viral gene expression. However, the function of many viral miRNAs remains poorly understood. In this study, we investigated the role of the BK polyomavirus (BKPyV) miRNA in regulating virus replication. The function of the polyomavirus miRNA was investigated in archetype BKPyV, which is the transmissible form of the virus and thought to establish a persistent infection in the host urinary tract. In agreement with previous studies, we show that the BKPyV miRNA targets early mRNAs. Importantly, we show that the miRNA plays a significant role in limiting archetype BKPyV replication in a natural host cell model of infection. This regulation is accomplished through the balance of regulatory elements located within the noncoding control region that control early gene expression and miRNA expression before genome replication. We therefore provide evidence for a unique function of the polyomavirus miRNA that may have important implications for the mechanism of viral persistence.
Model selection in cosmology

Model selection aims to determine which theoretical models are most plausible given some data, without necessarily considering preferred values of model parameters. A common model selection question is to ask when new data require introduction of an additional parameter, describing a newly discovered physical effect. We review model selection statistics, then focus on the Bayesian evidence, which implements Bayesian analysis at the level of models rather than parameters. We describe our CosmoNest code, the first computationally efficient implementation of Bayesian model selection in a cosmological context. We apply it to recent WMAP satellite data, examining the need for a perturbation spectral index differing from the scale-invariant (Harrison-Zel'dovich) case.
The effect of thermal history on the susceptibility of reef-building corals to thermal stress

SUMMARY The mutualistic relationship between corals and their unicellular dinoflagellate symbionts (Symbiodinium sp.) is a fundamental component within the ecology of coral reefs. Thermal stress causes the breakdown of the relationship between corals and their symbionts (bleaching). As with other organisms, this symbiosis may acclimate to changes in the environment, thereby potentially modifying the environmental threshold at which they bleach. While a few studies have examined the acclimation capacity of reef-building corals, our understanding of the underlying mechanism is still in its infancy. The present study focused on the role of recent thermal history in influencing the response of both corals and symbionts to thermal stress, using the reef-building coral Acropora aspera. The symbionts of corals that were exposed to 31°C for 48 h (pre-stress treatment) 1 or 2 weeks prior to a 6-day simulated bleaching event (when corals were exposed to 34°C) were found to have more effective photoprotective mechanisms. These mechanisms included changes in non-photochemical quenching and xanthophyll cycling. These differences in photoprotection were correlated with decreased loss of symbionts, with those corals that were not prestressed performing significantly worse, losing over 40% of their symbionts and having a greater reduction in photosynthetic efficiency. These results are important in that they show that thermal history, in addition to light history, can influence the response of reef-building corals to thermal stress and therefore have implications for the modeling of bleaching events. However, whether acclimation is capable of modifying the thermal threshold of corals sufficiently to cope as sea temperatures increase in response to global warming has not been fully explored. Clearly increases in sea temperatures that extend beyond 1–2°C will exhaust the extent to which acclimation can modify the thermal threshold of corals.
Public Sector Size and Corruption: Evidence from 290 Swedish Municipalities

In this paper, we use data from a corruption survey conducted among top politicians and high level civil servants in 290 Swedish municipalities in 2007 to investigate the effects of government size on corruption. We construct several measures of corruption based on the survey, and combine these corruption measures with detailed administrative municipality level data to estimate the effect of local government resources on corruption. In cross-sectional analysis, we find a robust and negative association between total public expenditure and corruption. When we use lagged population growth rates and age structure as instruments for expenditure in 2-stage-least-squares regressions, the point estimates remain negative, but are no longer significant. In contrast with standard political economy models, where a bigger public sector is typically assumed to cause problems with corruption and public office abuse, our results suggest that corruption pressures may be particularly high when government resources are limited.
Bayesian Integration of Information in Hippocampal Place Cells

Accurate spatial localization requires a mechanism that corrects for errors, which might arise from inaccurate sensory information or neuronal noise. In this paper, we propose that Hippocampal place cells might implement such an error correction mechanism by integrating different sources of information in an approximately Bayes-optimal fashion. We compare the predictions of our model with physiological data from rats. Our results suggest that useful predictions regarding the firing fields of place cells can be made based on a single underlying principle, Bayesian cue integration, and that such predictions are possible using a remarkably small number of model parameters.
Cyclin D1 and Ki-67 expression correlates to tumor staging in tongue squamous cell carcinoma

Background The immunohistochemical expression of Cyclin D1 and Ki-67 were analyzed in tongue squamous cell carcinomas (SCC), relating them to the clinical and morphological exhibition of these tumors. Material and Methods Twenty-nine patients fulfilled the inclusion criteria; clinical data included gender, age, ethnicity and use of licit drugs such as alcohol and tobacco. The TNM staging and histopathological differentiation grading was assessed for each case. In addition, T1 patients were gathered with T2 patients; and T3 patients were gathered with T4 patients to assemble two distinct groups: (T1/T2) and (T3/T4). Results The mean follow-up time was 24 months and 30% of the patients died as a consequence of the disease, while 23.3% lived with the disease and 46.7% lived lesion-free. T1 and T2 tumors showed statistically lesser Ki-67 and Cyclin D1 staining when compared to T3 and T4 tumors. Conclusions Ki-67 and Cyclin D1 pose as auxiliary tools when determining the progression of tongue SCC at the time of diagnosis. Key words:Carcinoma, squamous cell, cyclin D, immunohistochemistry, Ki-67 antigen, prognosis.
Voice Conversion from Unaligned Corpora Using Variational Autoencoding Wasserstein Generative Adversarial Networks

Building a voice conversion (VC) system from non-parallel speech corpora is challenging but highly valuable in real application scenarios. In most situations, the source and the target speakers do not repeat the same texts or they may even speak different languages. In this case, one possible, although indirect, solution is to build a generative model for speech. Generative models focus on explaining the observations with latent variables instead of learning a pairwise transformation function, thereby bypassing the requirement of speech frame alignment. In this paper, we propose a non-parallel VC framework with a variational autoencoding Wasserstein generative adversarial network (VAW-GAN) that explicitly considers a VC objective when building the speech model. Experimental results corroborate the capability of our framework for building a VC system from unaligned data, and demonstrate improved conversion quality.