Miracle-dz/UniFAR-FTUs huggingface dataset:
Are you listening? Brain activation associated with sustained nonspatial auditory attention in the presence and absence of stimulation

Neuroimaging studies investigating the voluntary (top‐down) control of attention largely agree that this process recruits several frontal and parietal brain regions. Since most studies used attention tasks requiring several higher‐order cognitive functions (e.g. working memory, semantic processing, temporal integration, spatial orienting) as well as different attentional mechanisms (attention shifting, distractor filtering), it is unclear what exactly the observed frontoparietal activations reflect. The present functional magnetic resonance imaging study investigated, within the same participants, signal changes in (1) a “Simple Attention” task in which participants attended to a single melody, (2) a “Selective Attention” task in which they simultaneously ignored another melody, and (3) a “Beep Monitoring” task in which participants listened in silence for a faint beep. Compared to resting conditions with identical stimulation, all tasks produced robust activation increases in auditory cortex, cross‐modal inhibition in visual and somatosensory cortex, and decreases in the default mode network, indicating that participants were indeed focusing their attention on the auditory domain. However, signal increases in frontal and parietal brain areas were only observed for tasks 1 and 2, but completely absent for task 3. These results lead to the following conclusions: under most conditions, frontoparietal activations are crucial for attention since they subserve higher‐order cognitive functions inherently related to attention. However, under circumstances that minimize other demands, nonspatial auditory attention in the absence of stimulation can be maintained without concurrent frontal or parietal activations. Hum Brain Mapp 35:2233–2252, 2014. © 2013 Wiley Periodicals, Inc.
Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo

Natural killer (NK) cells are lymphocytes of the innate immune system able to recognize and kill tumors lacking self-MHC class I molecules. This “missing-self” recognition is mediated by the lack of engagement of MHC class I-specific inhibitory NK cell receptors that include the killer cell Ig-like receptors (KIR) in humans and Ly49 molecules in mice. A promising immunotherapeutic strategy against MHC class I+ cancer cells is to block NK cell inhibitory receptors using monoclonal antibodies (mAb). However, interactions between MHC class I molecules and their inhibitory receptors are also required for the acquisition of NK cell functional competence, a process referred as to “education. ” In addition, inhibitory receptors are involved in self-tolerance on educated NK cells. Here, we developed a preclinical mouse model in which all NK cells are educated by a single transgenic inhibitory receptor, human KIR2DL3, through the engagement with its HLA-Cw3 ligand. This approach revealed that NK cells could be reprogrammed to control the development of mouse syngenic tumors in vivo. Moreover, in vivo anti-KIR mAb treatment induced the killing of HLA+ target cells without breaking self-tolerance. Finally, the long-term infusion of anti-KIR mAb neither abolished NK cell education nor tumor cell recognition. Therefore, these results strongly support the use of inhibitory receptor blockade in cancer patients.
Computational evaluation of cellular metabolic costs successfully predicts genes whose expression is deleterious

Significance Biologists frequently overexpress genes to learn about their cellular functions, and biotechnologists do so to construct novel metabolic pathways that produce valuable chemical compounds. However, gene overexpression often leads to deleterious consequences whose cause is unclear. Here, we present a computational method named Expression-Dependent Gene Effects (EDGE) that can successfully predict the deleterious effects resulting from overexpression of either native or foreign (originating in another species) metabolic genes. EDGE relies on genome-scale metabolic models, an emerging computational paradigm for studying metabolism in silico. Beyond its biotechnological significance, gene overexpression also plays an important role in human disease. We show EDGE’s applicability in the latter case by demonstrating its ability to detect toxic genes whose expression tends to be suppressed in cancer cells. Gene suppression and overexpression are both fundamental tools in linking genotype to phenotype in model organisms. Computational methods have proven invaluable in studying and predicting the deleterious effects of gene deletions, and yet parallel computational methods for overexpression are still lacking. Here, we present Expression-Dependent Gene Effects (EDGE), an in silico method that can predict the deleterious effects resulting from overexpression of either native or foreign metabolic genes. We first test and validate EDGE’s predictive power in bacteria through a combination of small-scale growth experiments that we performed and analysis of extant large-scale datasets. Second, a broad cross-species analysis, ranging from microorganisms to multiple plant and human tissues, shows that genes that EDGE predicts to be deleterious when overexpressed are indeed typically down-regulated. This reflects a universal selection force keeping the expression of potentially deleterious genes in check. Third, EDGE-based analysis shows that cancer genetic reprogramming specifically suppresses genes whose overexpression impedes proliferation. The magnitude of this suppression is large enough to enable an almost perfect distinction between normal and cancerous tissues based solely on EDGE results. We expect EDGE to advance our understanding of human pathologies associated with up-regulation of particular transcripts and to facilitate the utilization of gene overexpression in metabolic engineering.
Idiopathic Stabbing Headache (Jabs and Jolts Syndrome)

The clinical features of idiopathic stabbing headache (“jabs and jolts syndrome”) were studied in 38 patients who were diagnosed throughout a 1-year period. Mean age at the onset of symptoms was 47.1 years ± 14.5 (SD), and a clear female preponderance was demonstrated (female/male ratio=6.6), Painful attacks were ultrashort, i.e. virtually all attacks in more than two thirds of cases lasted only one second. The frequency of attacks varied immensely, ranging from 1 attach per year to 50 attacks daily. The pain paroxysms usually occurred with an irregular or sporadic temporal pattern. The localization of painful attacks was reported frequently as unifocal, usually in the orbital area, but also multifocal patterns were observed, the attacks frequently changing location from one area to the next. The majority of attacks occurred spontaneously, and accompanying phenomena were reported only rarely. Indomethacin treatment (75 mg daily) seemed to have a complete or partial effect in most patients treated as such (n = 17).
Design and Synthesis of Novel N-Arylsulfonyl-3-(2-yl-ethanone)-6-methylindole Derivatives as Inhibitors of HIV-1 Replication

Seven novel N-arylsulfonyl-3-(2-yl-ethanone)-6-methylindole derivatives 4a–f and 6 were readily synthesized and have been identified as inhibitors of human immunodeficiency virus type-1 (HIV-1) replication. Initial biological studies indicated that among these derivatives, N-(p-ethyl)phenylsulfonyl-3-[2-morpholinoethanone]-6-methylindole (4f) and N-(p-ethyl)phenylsulfonyl-3-[2-(5-phenyl-1,3,4-oxadiazole-2-yl-thio)ethanone]-6-methylindole (6) showed the most promising activity against HIV-1 replication. The effective concentration (EC50) and therapeutic index (TI) values of 4f and 6 were 9.42/4.62 μM, and >49.77/66.95, respectively. The cytotoxicity of these compounds has also been assessed. No significant cytotoxicities were found for any of these compounds.
A regularized kernel-based approach to unsupervised audio segmentation

We introduce a regularized kernel-based rule for unsupervised change detection based on a simpler version of the recently proposed kernel Fisher discriminant ratio. Compared to other kernel-based change detectors found in the literature, the proposed test statistic is easier to compute and has a known asymptotic distribution which can effectively be used to set the false alarm rate a priori. This technique is applied for segmenting tracks from TV shows, both for segmentation into semantically homogeneous sections (applause, movie, music, etc.) and for speaker diarization within the speech sections. On these tasks, the proposed approach outperforms other kernel-based tests and is competitive with a standard HMM-based supervised alternative.
Usefulness and Safety of Shortened Head‐Up Tilt Testing Potentiated with Sublingual Glyceryl Trinitrate in Older Patients with Recurrent Unexplained Syncope

OBJECTIVES: To evaluate the sensitivity and tolerability of shortened, glyceryl trinitrate (GTN)‐potentiated, head‐up tilt test (HUT) in patients older and younger than 65 with unexplained syncope and to compare the specificity of GTN‐potentiated HUT (GTN‐HUT) in older and younger controls.
Characterization and localization of the KpsE protein of Escherichia coli K5, which is involved in polysaccharide export

In Escherichia coli with group II capsules, the synthesis and cellular expression of capsular polysaccharide are encoded by the kps gene cluster. This gene cluster is composed of three regions. The central region 2 encodes proteins involved in polysaccharide synthesis, and the flanking regions 1 and 3 direct the translocation of the finished polysaccharide across the cytoplasmic membrane and its surface expression. The kps genes of the K5 polysaccharide, which is a group II capsular polysaccharide, have been cloned and sequenced. Region 1 contains the kpsE, -D, -U, -C, and -S genes. In this communication we describe the KpsE protein, the product of the kpsE gene. A truncated kpsE gene was fused with a truncated beta-galactosidase gene to generate a fusion protein containing the first 375 amino acids of beta-galactosidase and amino acids 67 to 382 of KpsE (KpsE'). This fusion protein was isolated and cleaved with factor Xa, and the purified KpsE' was used to immunize rabbits. Intact KpsE was extracted from the membranes of a KpsE-overexpressing recombinant strain with octyl-beta-glucoside. It was purified by affinity chromatography with immobilized anti-KpsE antibodies. Cytofluorometric analysis using the anti-KpsE antibodies with whole cells and spheroplasts, as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting (immunoblotting) of proteins from spheroplasts and membranes before and after treatment with proteinase K, indicated that the KpsE protein is associated with the cytoplasmic membrane and has an exposed periplasmic domain. By TnphoA mutagenesis and by constructing beta-lactamase fusions to the KpseE protein, it was possible to determine the topology of the KpsE protein within the cytoplasmic membrane.
Influence of minimum quantity lubrication parameters on grind-hardening process

ABSTRACT Currently, dry grind-hardening has been studied to achieve a deep grinding harden layer. For dry grind-hardening process, the ground surface may have a poor surface quality. In our previous research, minimum quantity lubrication (MQL) has been proved as an effective way to improve the surface quality in grind-hardening process. Unfortunately, the relationship between the surface quality and parameters of MQL is still not clear. In this paper, different spraying parameters (fluid flow, air pressure, nozzle location, spraying distance) are investigated in surface grinding experiments of annealed steel AISI 5140. Grind-hardening performances are analyzed for grinding force and surface quality, such as surface roughness, micro-hardness, and grinding harden layer depth. Consequently, the results show that MQL can improve the grinding surface roughness and the micro-hardness of the grinding harden layer. The surface roughness can be improved with a better lubrication, which can be achieved with the appropriate spray direction. The surface roughness and the harden layer depth are reduced with the increasing fluid flow rate and air pressure, while they increase with the spraying distance.
Formation and structure of the three Neptune-mass planets system around HD 69830

Since the discovery of the first giant planet outside the solar system in 1995 (Mayor & Queloz 1995, Nature, 378, 355), more than 180 extrasolar planets have been discovered. With improving detection capabilities, a new class of planets with masses 5-20 times larger than the Earth, at close distance from their parent star is rapidly emerging. Recently, the first system of three Neptune-mass planets has been discovered around the solar type star HD 69830 (Lovis et al. 2006, Nature, 441, 305). Here, we present and discuss a possible formation scenario for this planetary system based on a consistent coupling between the extended core accretion model and evolutionary models (Alibert et al. 2005a, AA Baraffe et al. 2004, AA Baraffe et al. 2006, A&A, 450, 1221). We show that the innermost planet formed from an embryo having started inside the iceline is composed essentially of a rocky core surrounded by a tiny gaseous envelope. The two outermost planets started their formation beyond the iceline and, as a consequence, accrete a substantial amount of water ice during their formation. We calculate the present day thermodynamical conditions inside these two latter planets and show that they are made of a rocky core surrounded by a shell of fluid water and a gaseous envelope.
Field Response of the Twig Beetle, Pityophthorus pubescens, to the Aggregation Pheromone, (E)-(+)-pityol, is not Inhibited by (E)-(-)-pityol, and Evidence of Monogyny

Abstract Field studies were conducted to determine the flight response of the twig beetle Pityophthorus pubescens (Marsham) (Coleoptera: Curculionidae: Scolytinae) to the potential aggregation pheromone component, (E)-(+)-pityol, and its racemic form, (E)-(±)-pityol, in different Pinus spp. L. (Pinales: Pinaceae) stands in the Basque Country (Northern Spain). Both (E)-(+)-pityol and (E)-(±)-pityol equally attracted more males than females, and they were all significantly different from the blank controls. Data about P. pubescens gallery systems in naturally infested P. radiata D. Don branches are also provided. The presence of one male and one female was the most common gallery habitation found in debarked twigs. Current results suggest that P. pubescens may be monogynous and females might mediate the aggregation of mating partners.
Rapid evolution of the human gut virome

Humans are colonized by immense populations of viruses, which metagenomic analysis shows are mostly unique to each individual. To investigate the origin and evolution of the human gut virome, we analyzed the viral community of one adult individual over 2.5 y by extremely deep metagenomic sequencing (56 billion bases of purified viral sequence from 24 longitudinal fecal samples). After assembly, 478 well-determined contigs could be identified, which are inferred to correspond mostly to previously unstudied bacteriophage genomes. Fully 80% of these types persisted throughout the duration of the 2.5-y study, indicating long-term global stability. Mechanisms of base substitution, rates of accumulation, and the amount of variation varied among viral types. Temperate phages showed relatively lower mutation rates, consistent with replication by accurate bacterial DNA polymerases in the integrated prophage state. In contrast, Microviridae, which are lytic bacteriophages with single-stranded circular DNA genomes, showed high substitution rates (>10−5 per nucleotide each day), so that sequence divergence over the 2.5-y period studied approached values sufficient to distinguish new viral species. Longitudinal changes also were associated with diversity-generating retroelements and virus-encoded Clustered Regularly Interspaced Short Palindromic Repeats arrays. We infer that the extreme interpersonal diversity of human gut viruses derives from two sources, persistence of a small portion of the global virome within the gut of each individual and rapid evolution of some long-term virome members.
Parallelizing Compiler Techniques Based on Linear Inequalities

Shared-memory multiprocessors, built out of the latest microprocessors, are becoming a widely available class of computationally powerful machines. These affordable multiprocessors can potentially deliver supercomputer-like performance to the general public. To effectively harness the power of these machines it is important to find all the available parallelism in programs. The Stanford SUIF interprocedural parallelizer we have developed is capable of detecting coarser granularity of parallelism in sequential scientific applications than previously possible. Specifically, it can parallelize loops that span numerous procedures and hundreds of lines of codes, frequently requiring modifications to array data structures such as array privatization. Measurements from several standard benchmark suites demonstrate that aggressive interprocedural analyses can substantially advance the capability of automatic parallelization technology. However, locating parallelism is not sufficient in achieving high performance. It is critical to make effective use of the memory hierarchy. In parallel applications, false sharing and cache conflicts between processors can significantly reduce performance. We have developed the first compiler that automatically performs a full suite of data transformations (a combination of transposing, strip-mining and padding). The performance of many benchmarks improves drastically after the data transformations. We introduce a framework based on systems of linear inequalities for developing compiler algorithms. Many of the whole program analyses and aggressive optimizations in our compiler employ this framework. Using this framework general solutions to many compiler problems can be found systematically.
Actions on blood clotting of peptide material in human brain: with special reference to enhancement of antithrombin activity.

A COR DIN G T 0 SEE G E R S et al. (1954) there are four mechanisms or properties which might be called 'antithrombin' and to which the numbers I, II, III and IV have been given. Antithrombin I refers to the adsorption of thrombin on fibrin, antithrombin II to the cofactor of heparin in plasma or serum which interferes with the action of thrombin on fibrinogen. Antithrombin III is usually called the 'normal' antithrombin of plasma or serum; it neutralizes thrombin, and in the reaction both antithrombin and thrombin disappear. Antithrombin IV is an additional form of antithrombin which appears in plasma when prothrombin is activated to form thrombin. Antithrombin IV has been demonstrated in dog plasma but whether it is a property of human plasma is uncertain (Seegers et al., 1954). In the present paper, unless otherwise stated, the term antithrombin refers to the 'normal' or antithrombin III. Several substances have been used to abolish or at least antagonize antithrombin activity such as ether (Seegers et al., 1954), ethanol (Sternberger, 1947) and phenols (Fantl, 1954). But, so far as I know, enhancement or acceleration of the action of antithrombin has not been recognized or described previously. This form of activity was discovered by accident during prothrombin conversion experiments and the enhancing agent was found to be material of peptide nature in human brain. The material was present in some samples of brain thromboplastin and therefore had practical significance for blood clotting experiments as well as theoretical interest. Another new observation was that peptide preparations of brain, and some other tissues, retarded in vitro blood clotting by other mechanisms.
Speech Outcomes After Clinically Indicated Posterior Pharyngeal Flap Takedown

BackgroundVelopharyngeal insufficiency affects as many as one in three patients after cleft palate repair. Correction using a posterior pharyngeal flap (PPF) has been shown to improve clinical speech symptomatology; however, PPFs can be complicated by hyponasality and obstructive sleep apnea. The goal of this study was to assess if speech outcomes revert after clinically indicated PPF takedown. MethodsThe cleft-craniofacial database of the Children's Hospital of Pittsburgh at the University of Pittsburgh Medical Center was retrospectively queried to identify patients with a diagnosis of velopharyngeal insufficiency treated with PPF who ultimately required takedown. Using the Pittsburgh Weighted Speech Score (PWSS), preoperative scores were compared to those after PPF takedown. Outcomes after 2 different methods of PPF takedown (PPF takedown alone or PPF takedown with conversion to Furlow palatoplasty) were stratified and cross-compared. ResultsA total of 64 patients underwent takedown of their PPF. Of these, 18 patients underwent PPF takedown alone, and 46 patients underwent PPF takedown with conversion to Furlow Palatoplasty. Patients averaged 12.43 (range, 3.0–22.0)(SD: 3.93) years of age at the time of PPF takedown, and 58% were men. Demographics between groups were not statistically different. The mean duration of follow-up after surgery was 38.09 (range, 1–104) (SD, 27.81) months. For patients undergoing PPF takedown alone, the mean preoperative and postoperative PWSS was 3.83 (range, 0.0–23.0) (SD, 6.13) and 4.11 (range, 0.0–23.0) (SD, 5.31), respectively (P = 0.89). The mean change in PWSS was 0.28 (range, −9.0 to 7.0) (SD, 4.3). For patients undergoing takedown of PPF with conversion to Furlow palatoplasty, the mean preoperative and postoperative PWSS was 6.37 (range, 0–26) (SD, 6.70) and 3.11 (range, 0.0–27.0) (SD, 4.14), respectively (P < 0.01). The mean change in PWSS was −3.26 (range, −23.0 to 4.0) (SD, 4.3). For all patients, the mean preoperative PWSS was 5.66 (range, 0.0–26) (SD, 6.60) and 3.39 (range, 0.0–27) (SD, 4.48), respectively (P < 0.05). The mean change in PWSS was −2.26 (range, −23.0 to 7) (SD, 5.7). There was no statistically significant regression in PWSS for either surgical intervention. Two patients in the PPF takedown alone cohort demonstrated deterioration in PWSS that warranted delayed conversion to Furlow palatoplasty. Approximately 90% of patients, who undergo clinically indicated PPF takedown alone, without conversion to Furlow Palatoplasty, will show no clinically significant reduction in speech. ConclusionsAlthough there is concern that PPF takedown may degrade speech, this study finds that surgical takedown of PPF, when clinically indicated, does not result in a clinically significant regression of speech.