Miracle-dz/UniFAR-FTUs huggingface dataset:
Genome‐wide significant association between alcohol dependence and a variant in the ADH gene cluster

Alcohol dependence (AD) is an important contributory factor to the global burden of disease. The etiology of AD involves both environmental and genetic factors, and the disorder has a heritability of around 50%. The aim of the present study was to identify susceptibility genes for AD by performing a genome‐wide association study (GWAS). The sample comprised 1333 male in‐patients with severe AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 2168 controls. These included 487 patients and 1358 controls from a previous GWAS study by our group. All individuals were of German descent. Single‐marker tests and a polygenic score‐based analysis to assess the combined contribution of multiple markers with small effects were performed. The single nucleotide polymorphism (SNP) rs1789891, which is located between the ADH1B and ADH1C genes, achieved genome‐wide significance [P = 1.27E–8, odds ratio (OR) = 1.46]. Other markers from this region were also associated with AD, and conditional analyses indicated that these made a partially independent contribution. The SNP rs1789891 is in complete linkage disequilibrium with the functional Arg272Gln variant (P = 1.24E–7, OR = 1.31) of the ADH1C gene, which has been reported to modify the rate of ethanol oxidation to acetaldehyde in vitro. A polygenic score‐based approach produced a significant result (P = 9.66E–9). This is the first GWAS of AD to provide genome‐wide significant support for the role of the ADH gene cluster and to suggest a polygenic component to the etiology of AD. The latter result may indicate that many more AD susceptibility genes still await identification.
Fast-Evolving Mitochondrial DNA in Ceriantharia: A Reflection of Hexacorallia Paraphyly?

The low evolutionary rate of mitochondrial genes in Anthozoa has challenged their utility for phylogenetic and systematic purposes, especially for DNA barcoding. However, the evolutionary rate of Ceriantharia, one of the most enigmatic “orders” within Anthozoa, has never been specifically examined. In this study, the divergence of mitochondrial DNA of Ceriantharia was compared to members of other Anthozoa and Medusozoa groups. In addition, nuclear markers were used to check the relative phylogenetic position of Ceriantharia in relation to other Cnidaria members. The results demonstrated a pattern of divergence of mitochondrial DNA completely different from those estimated for other anthozoans, and phylogenetic analyses indicate that Ceriantharia is not included within hexacorallians in most performed analyses. Thus, we propose that the Ceriantharia should be addressed as a separate clade.
Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). II. Comparison of hybridomas derived by lipopolysaccharide stimulation and secondary protein immunization

We have obtained the complete variable region mRNA sequences of 11 LPS- derived and 14 secondary immunization-derived monoclonal IgM anti-IgG antibodies (rheumatoid factors, RFs). A comparative analysis of these sequences showed that monoclonal RFs derived after polyclonal activation are structurally very similar to RFs derived after secondary protein immunization. This study was undertaken to evaluate the potential relationship between two previously described phenomena: (a) during a secondary response to a protein antigen, RF is produced in quantities that equal or exceed the immunogen-specific antibody; and (b) the frequency of B cells that make RF after polyclonal activation is quite high; 3-10%. It has been unclear whether LPS-stimulated cells that produce IgM anti-IgG that is detected by an in vitro assay are related to the cells that produce RF after in vivo stimulation. The similarity of the antigen receptors found in the two types of RF, however, suggests that most or all of the RF-producing B cells detected after LPS stimulation would also be stimulated during the secondary immune response. Thus, the presence of relatively large number of B cells that can make RF after nonspecific stimulation provides an explanation for the magnitude of RF production accompanying the secondary immune response.
Interactions of full‐fat canola seed, oat hulls as an insoluble fiber source and pellet temperature for nutrient utilization and growth performance of broiler chickens

&NA; The effectiveness of the addition of oat hulls (OH) as an insoluble fiber for improving nutrient digestibility and performance of birds fed diets containing full‐fat canola seed (CS) was studied. A 2 × 2 × 2 factorial arrangement of treatments was used to assess the main effects of canola source (CS vs canola meal plus oil as control), OH (0 or 3%), pellet temperature (75 and 90°C) and their interactions. A total of 576 male day‐old Ross 308 chickens were assigned to 8 experimental treatments, each replicated 6 times (12 birds per replicate). All birds were fed a same commercial starter diet for the first 10 d of age. Canola meal and canola oil in the control diets were replaced with CS at 11.6% and 13.5% in the grower (d 10 to 24) and finisher (d 24 to 35) diets, respectively. An interaction was observed between canola source and OH led to improved body weight gain (P < 0.01) and FCR (P < 0.05) in birds fed the combination of CS and OH in grower phase. Pelleting temperature at 75 vs 90°C did not affect performance of broilers. Birds fed diets containing OH had heavier gizzards at 24 and 35 d of age. Inclusion of CS in the diets depressed fat digestibility at d 24 (P < 0.001) and AME of the grower diets. At d 35, there was a significant interaction (P < 0.05) between CS and pellet temperature where birds fed CS diets pelleted at 75°C had higher fat digestibility than birds fed CS pelleted at 90°C. Regardless of canola source or pellet temperature, OH increased fat utilization at d 35 (P < 0.001) but had no effect on AME of the grower diets. In conclusion, CS can replace supplemental oil in broiler diets when an adequate source of insoluble fiber is included in the diet, which may help to maintain feed intake of broilers fed CS in steam‐pelleted diets.
DNA sequence analysis of the YCN2 region of chromosome XI in Saccharomyces cerevisiae

A 6·8 kbp DNA fragment localized to the left arm of chromosome XI from Saccharomyces cerevisiae was sequenced and analysed (EMBL accession no. X69765). Two genes involved in protein phosphatase activity were identified: YCN2 and an open reading frame encoding a protein that shares 46% amino acid identity with the sds22+ protein from Schizosaccharomyces pombe. A comparison of the genomic YCN2 sequence with the published cDNA sequence suggests the presence of an intron near the 5′ end of the gene. Further sequence analysis suggests the presence of three additional genes near YCN2: a mitochondrial acyl‐carrier protein, a gene encoding a putative hydrophobic protein, and a new gene coding for a tRNALeu (UAA) isoacceptor located near a delta sequence.
Altered neural activation pattern during teeth clenching in temporomandibular disorders.

OBJECTIVE The aim was to explore the neural activations during teeth clenching in TMDs patients pre- and post-treatment. SUBJECTS AND METHODS Thirty TMDs patients and 20 controls underwent clinical evaluations and functional magnetic resonance imaging with a teeth clenching task. Eleven patients received repeat evaluation and imaging after wearing a stabilization splint for 3 months. RESULTS During teeth clench, the TMDs patients showed decreased positive activity in the left precentral gyrus, right and left inferior temporal gyrus, and left cerebellum and increased negative activations in the right medial prefrontal cortex (P < 0.05 after AlphaSim correction). The 11 TMDs patients after treatment showed a return to normal neural activity in these areas. No brain areas in TMDs patients showed differences in activation after treatment compared with the controls, except for an increase in activation in the right cerebellum in the 11 TMDs patients (P < 0.05 after AlphaSim correction). CONCLUSION Decreased activations in cerebral areas associated with motor and cognitive functions in TMDs patients during teeth clenching were observed. Normalized activations of these areas happened in patients after routine treatment. These findings may facilitate the understanding of TMDs pathogenesis and the therapeutic mechanisms of the stabilization splint.
Long-term cardiovascular mortality in patients with differentiated thyroid carcinoma: an observational study.

PURPOSE The primary aim was to study the risk of cardiovascular mortality in patients with differentiated thyroid carcinoma (DTC). Secondary aims were to evaluate all-cause mortality and explore the relation between thyroid-stimulating hormone (TSH; also known as thyrotropin) level and these outcome parameters. PATIENTS AND METHODS Subjects from two cohorts were retrospectively compared by Cox regression analyses; 524 patients with DTC and 1,572 sex- and age-matched controls from a large population-based study in the same geographic region. RESULTS Mean age plus or minus standard deviation was 49 ± 14 years. Median follow-up was 8.5 years (interquartile range [IQR], 4.1 to 15.9 years) for patients with DTC and 10.5 years (IQR, 9.9 to 10.9 years) for controls. One hundred patients with DTC (19.1%) died, 22 (4.2%) as a result of cardiovascular disease, 39 (7.4%) as a result of DTC, and 39 (7.4%) as a result of other/unknown causes. Eighty-five controls (5.4%) died, 24 (1.5%) as a result of cardiovascular disease and 61 (3.9%) as a result of other/unknown causes. Patients with DTC had an increased risk of cardiovascular and all-cause mortality (hazard ratios [HRs], 3.35 [95% CI, 1.66 to 6.74] and 4.40 [95% CI, 3.15 to 6.14], respectively, adjusted for age, sex, and cardiovascular risk factors). Within the DTC group, TSH level was predictive for cardiovascular mortality; the adjusted HR was 3.08 (95% CI, 1.32 to 7.21) for each 10-fold decrease in geometric mean TSH level. CONCLUSION The risk of cardiovascular and all-cause mortality is increased in patients with DTC, independent of age, sex, and cardiovascular risk factors. A lower TSH level is associated with increased cardiovascular mortality, supporting the current European Thyroid Association and the American Thyroid Association guidelines of tempering TSH suppression in patients with low risk of cancer recurrence. Furthermore, patients with DTC may benefit from assessment and treatment of cardiovascular risk factors.
Transcriptome profiling of dorsal root ganglia in a rat model of complex regional pain syndrome type-I reveals potential mechanisms involved in pain

Purpose: Complex regional pain syndrome type-I (CRPS-I) is a progressive and devastating pain condition, which remains clinically challenging. The mechanisms of CRPS-I still remain largely unknown. We aim to identify transcriptome profiles of genes relevant to pain mechanisms and major pathways involved in CRPS-I. Methods: A rat model of chronic post-ischemia pain (CPIP) was established to mimic CRPS-I. RNA-sequencing (RNA-Seq) was used to profile transcriptome of L4-6 dorsal root ganglia (DRGs) of a rat model of CRPS-I. Results: CPIP model rats developed persistent mechanical/thermal hyperalgesia in ipsilateral hind paw. RNA-Seq identified a total of 295 differentially expressed genes (DEGs), including 195 up- and 100 downregulated, in ipsilateral DRGs of CPIP rats compared with sham rats. The expression of several representative genes was confirmed by qPCR. Functional analysis of DEGs revealed that the most significant enriched biological processes of upregulated genes include response to lipopolysaccharide, inflammatory response and cytokine activity, which are all important mechanisms mediating pain. We further screened DEGs implicated in pain progress, genes enriched in small- to medium-sized sensory neurons and enriched in TRPV1-lineage nociceptors. By comparing our dataset with other published datasets of neuropathic or inflammatory pain models, we identified a core set of genes and pathways that extensively participate in CPIP and other neuropathic pain states. Conclusion: Our study identified transcriptome gene changes in DRGs of an animal model of CRPS-I and could provide insights into identifying promising genes or pathways that can be potentially targeted to ameliorate CRPS-I.
A General Process Model: Application to Unanticipated Fault Diagnosis

The improvement of the detection and diagnosis capability for the unanticipated fault is a tendency in the research and application of fault diagnosis. In this paper, some notions and the basic principles for the unanticipated fault detection and diagnosis are given. A general process model applied to the diagnosis for the unanticipated fault is designed, by adopting a three-layer progressive structure, which is comprised of an inherent detection layer, an unanticipated isolation layer and an unanticipated recognition layer. Several key problems in the general process model are analyzed. The model and methods proposed in this paper are driven by pure data and they can detect and diagnose the unanticipated fault. The approach is evaluated by using an example of a satellite’s attitude control system, and excellent results have been obtained.
A Generalization of Sleep Sets Based on Operator Sequence Redundancy

Pruning techniques have recently been shown to speed up search algorithms by reducing the branching factor of large search spaces. One such technique is sleep sets, which were originally introduced as a pruning technique for model checking, and which have recently been investigated on a theoretical level for planning. In this paper, we propose a generalization of sleep sets and prove its correctness. While the original sleep sets were based on the commutativity of operators, generalized sleep sets are based on a more general notion of operator sequence redundancy. As a result, our approach dominates the original sleep sets variant in terms of pruning power. On a practical level, our experimental evaluation shows the potential of sleep sets and their generalizations on a large and common set of planning benchmarks.
Determining Verb Phrase Referents in Dialogs

This paper discusses two problems central to the interpretation of utterances: determining the relationship between actions described in an utterance and events in the world, and inferring the "state of the world" from utterances. Knowledge of the language, knowledge about the general subject being discussed, and knowledge about the current situation are all necessary for this. The problem of determining an action referred to by a verb phrase is analogous to the problem of determining the object referred to by a noun phrase.This paper presents an approach to the problem of determining verb phrase referents in which knowledge about language, the subject area, and the dialog itself is combined to interpret such references. Presented and discussed are the kinds of knowledge necessary for interpreting references to actions, as well as algorithms for using that knowledge in interpreting dialog utterances about ongoing tasks and for drawing inferences about the task situation that are based on a given interpretation.
Thread scheduling mechanisms for multiple-context parallel processors

Scheduling tasks to efficiently use the available processor resources is crucial to minimizing the runtime of applications on shared-memory parallel processors. One factor that contributes to poor processor utilization is the idle time caused by long latency operations, such as remote memory references or processor synchronization operations. One way of tolerating this latency is to use a processor with multiple hardware contexts that can rapidly switch to executing another thread of computation whenever a long latency operation occurs, thus increasing processor utilization by overlapping computation with communication. Although multiple contexts are effective for tolerating latency, this effectiveness can be limited by memory and network bandwidth, by cache interference effects among the multiple contexts, and by critical tasks sharing processor resources with less critical tasks. This thesis presents techniques that increase the effectiveness of multiple contexts by intelligently scheduling threads to make more efficient use of processor pipeline, bandwidth, and cache resources. This thesis proposes thread prioritization as a fundamental mechanism for directing the thread schedule on a multiple-context processor. A priority is assigned to each thread either statically or dynamically and is used by the thread scheduler to decide which threads to load in the contexts, and to decide which context to switch to on a context switch. We develop a multiple-context model that integrates both cache and network effects, and shows how thread prioritization can both maintain high processor utilization, and limit increases in critical path runtime caused by multithreading. The model also shows that in order to be effective in bandwidth limited applications, thread prioritization must be extended to prioritize memory requests. We show how simple hardware can prioritize the running of threads in the multiple contexts, and the issuing of requests to both the local memory and the network. Simulation experiments show how thread prioritization is used in a variety of applications. Thread prioritization can improve the performance of synchronization primitives by minimizing the number of processor cycles wasted in spinning and devoting more cycles to critical threads. Thread prioritization can be used in combination with other techniques to improve cache performance and minimize cache interference between different working sets in the cache. For applications that are critical path limited, thread prioritization can improve performance by allowing processor resources to be devoted preferentially to critical threads. These experimental results show that thread prioritization is a mechanism that can be used to implement a wide range of scheduling policies.
Roles of Subthreshold Calcium Current and Sodium Current in Spontaneous Firing of Mouse Midbrain Dopamine Neurons

We used a preparation of acutely dissociated neurons to quantify the ionic currents driving the spontaneous firing of substantia nigra pars compacta neurons, isolated from transgenic mice in which the tyrosine hydroxylase promoter drives expression of human placental alkaline phosphatase (PLAP) on the outer surface of the cell membrane. Dissociated neurons identified by fluorescent antibodies to PLAP showed firing properties similar to those of dopaminergic neurons in brain slice, including rhythmic spontaneous firing of broad action potentials and, in some cells, rhythmic oscillatory activity in the presence of tetrodotoxin (TTX). Spontaneous activity in TTX had broader, smaller spikes than normal pacemaking and was stopped by removal of external calcium. Normal pacemaking was also consistently silenced by replacement of external calcium by cobalt and was slowed by more specific calcium channel blockers. Nimodipine produced a slowing of pacemaking frequency. Pacemaking was also slowed by the P/Q-channel blocker ω-Aga-IVA, but the N-type channel blocker ω-conotoxin GVIA had no effect. In voltage-clamp experiments, using records of pacemaking as command voltage, cobalt-sensitive current and TTX-sensitive current were both sizeable at subthreshold voltages between spikes. Cobalt-sensitive current was consistently larger than TTX-sensitive current at interspike voltages from −70 to −50 mV, with TTX-sensitive current larger at voltages positive to −45 mV. These results support previous evidence for a major role of voltage-dependent calcium channels in driving pacemaking of midbrain dopamine neurons and suggest that multiple calcium channel types contribute to this function. The results also show a significant contribution of subthreshold TTX-sensitive sodium current.
Unsupervised Learning of Deep Features for Music Segmentation

Music segmentation refers to the dual problem of identifying boundaries between, and labeling, distinct music segments, e.g., the chorus, verse, bridge etc. in popular music. The performance of a range of music segmentation algorithms has been shown to be dependent on the audio features chosen to represent the audio. Some approaches have proposed learning feature transformations from music segment annotation data, although, such data is time consuming or expensive to create and as such these approaches are likely limited by the size of their datasets. While annotated music segmentation data is a scarce resource, the amount of available music audio is much greater. In the neighboring field of semantic audio unsupervised deep learning has shown promise in improving the performance of solutions to the query-by-example and sound classification tasks. In this work, unsupervised training of deep feature embeddings using convolutional neural networks (CNNs) is explored for music segmentation. The proposed techniques exploit only the time proximity of audio features that is implicit in any audio timeline. Employing these embeddings in a classic music segmentation algorithm is shown not only to significantly improve the performance of this algorithm, but obtain state of the art performance in unsupervised music segmentation.
The Average Common Substring Approach to Phylogenomic Reconstruction

We describe a novel method for efficient reconstruction of phylogenetic trees, based on sequences of whole genomes or proteomes, whose lengths may greatly vary. The core of our method is a new measure of pairwise distances between sequences. This measure is based on computing the average lengths of maximum common substrings, which is intrinsically related to information theoretic tools (Kullback-Leibler relative entropy). We present an algorithm for efficiently computing these distances. In principle, the distance of two l long sequences can be calculated in O(l) time. We implemented the algorithm using suffix arrays our implementation is fast enough to enable the construction of the proteome phylogenomic tree for hundreds of species and the genome phylogenomic forest for almost two thousand viruses. An initial analysis of the results exhibits a remarkable agreement with "acceptable phylogenetic and taxonomic truth. " To assess our approach, our results were compared to the traditional (single-gene or protein-based) maximum likelihood method. The obtained trees were compared to implementations of a number of alternative approaches, including two that were previously published in the literature, and to the published results of a third approach. Comparing their outcome and running time to ours, using a "traditional" trees and a standard tree comparison method, our algorithm improved upon the "competition" by a substantial margin. The simplicity and speed of our method allows for a whole genome analysis with the greatest scope attempted so far. We describe here five different applications of the method, which not only show the validity of the method, but also suggest a number of novel phylogenetic insights.