Miracle-dz/UniFAR-FTUs huggingface dataset:
Ephemeral protein binding to DNA shapes stable nuclear bodies and chromatin domains

Fluorescence microscopy reveals that the contents of many (membrane-free) nuclear "bodies" exchange rapidly with the soluble pool whilst the underlying structure persists; such observations await a satisfactory biophysical explanation. To shed light on this, we perform large-scale Brownian dynamics simulations of a chromatin fiber interacting with an ensemble of (multivalent) DNA-binding proteins; these proteins switch between two states – active (binding) and inactive (non-binding). This system provides a model for any DNA-binding protein that can be modified post-translationally to change its affinity for DNA (e.g., like the phosphorylation of a transcription factor). Due to this out-of-equilibrium process, proteins spontaneously assemble into clusters of self-limiting size, as individual proteins in a cluster exchange with the soluble pool with kinetics like those seen in photo-bleaching experiments. This behavior contrasts sharply with that exhibited by "equilibrium", or non-switching, proteins that exist only in the binding state; when these bind to DNA non-specifically, they form clusters that grow indefinitely in size. Our results point to post-translational modification of chromatin-bridging proteins as a generic mechanism driving the self-assembly of highly dynamic, non-equilibrium, protein clusters with the properties of nuclear bodies. Such active modification also reshapes intra-chromatin contacts to give networks resembling those seen in topologically-associating domains, as switching markedly favors local (short-range) contacts over distant ones.
Relationships between work task types, complexity and dwell time of information resources

Information seeking research often reports about types of information resources, ways of acquiring them and opinions on their importance in various professions. Based on self-reporting, these findings are affected by human memory and rationalisation. This article proposes a new way of studying information resource use – based on dwell time in the context provided by concrete work tasks. We use log data of 21 information workers from six organisations to analyse how work task complexity is connected to the time used in various information resources; how task complexity is connected to information resource use in different task types. Unlike traditionally, our findings consist of objective data on which resource types are used, and for how long, in work tasks of varying complexity and type. For example, the findings suggest that growing work task complexity increases the dwell time in local personal computer (PC) resources; these resources are especially popular in intellectual tasks. Such findings help understand factors affecting information resource use. Likewise, they help focus attention on most time-consuming aspects of task-based information interaction when developing support for work.
Complete Genome Sequence of Borrelia afzelii K78 and Comparative Genome Analysis

The main Borrelia species causing Lyme borreliosis in Europe and Asia are Borrelia afzelii, B. garinii, B. burgdorferi and B. bavariensis. This is in contrast to the United States, where infections are exclusively caused by B. burgdorferi. Until to date the genome sequences of four B. afzelii strains, of which only two include the numerous plasmids, are available. In order to further assess the genetic diversity of B. afzelii, the most common species in Europe, responsible for the large variety of clinical manifestations of Lyme borreliosis, we have determined the full genome sequence of the B. afzelii strain K78, a clinical isolate from Austria. The K78 genome contains a linear chromosome (905,949 bp) and 13 plasmids (8 linear and 5 circular) together presenting 1,309 open reading frames of which 496 are located on plasmids. With the exception of lp28-8, all linear replicons in their full length including their telomeres have been sequenced. The comparison with the genomes of the four other B. afzelii strains, ACA-1, PKo, HLJ01 and Tom3107, as well as the one of B. burgdorferi strain B31, confirmed a high degree of conservation within the linear chromosome of B. afzelii, whereas plasmid encoded genes showed a much larger diversity. Since some plasmids present in B. burgdorferi are missing in the B. afzelii genomes, the corresponding virulence factors of B. burgdorferi are found in B. afzelii on other unrelated plasmids. In addition, we have identified a species specific region in the circular plasmid, cp26, which could be used for species determination. Different non-coding RNAs have been located on the B. afzelii K78 genome, which have not previously been annotated in any of the published Borrelia genomes.
Reproducibility of Lobar Perfusion and Ventilation Quantification Using SPECT/CT Segmentation Software in Lung Cancer Patients

Planar perfusion scintigraphy with 99mTc-labeled macroaggregated albumin is often used for pretherapy quantification of regional lung perfusion in lung cancer patients, particularly those with poor respiratory function. However, subdividing lung parenchyma into rectangular regions of interest, as done on planar images, is a poor reflection of true lobar anatomy. New tridimensional methods using SPECT and SPECT/CT have been introduced, including semiautomatic lung segmentation software. The present study evaluated inter- and intraobserver agreement on quantification using SPECT/CT software and compared the results for regional lung contribution obtained with SPECT/CT and planar scintigraphy. Methods: Thirty lung cancer patients underwent ventilation–perfusion scintigraphy with 99mTc-macroaggregated albumin and 99mTc-Technegas. The regional lung contribution to perfusion and ventilation was measured on both planar scintigraphy and SPECT/CT using semiautomatic lung segmentation software by 2 observers. Interobserver and intraobserver agreement for the SPECT/CT software was assessed using the intraclass correlation coefficient, Bland–Altman plots, and absolute differences in measurements. Measurements from planar and tridimensional methods were compared using the paired-sample t test and mean absolute differences. Results: Intraclass correlation coefficients were in the excellent range (above 0.9) for both interobserver and intraobserver agreement using the SPECT/CT software. Bland–Altman analyses showed very narrow limits of agreement. Absolute differences were below 2.0% in 96% of both interobserver and intraobserver measurements. There was a statistically significant difference between planar and SPECT/CT methods (P < 0.001) for quantification of perfusion and ventilation for all right lung lobes, with a maximal mean absolute difference of 20.7% for the right middle lobe. There was no statistically significant difference in quantification of perfusion and ventilation for the left lung lobes using either method; however, absolute differences reached 12.0%. The total right and left lung contributions were similar for the two methods, with a mean difference of 1.2% for perfusion and 2.0% for ventilation. Conclusion: Quantification of regional lung perfusion and ventilation using SPECT/CT-based lung segmentation software is highly reproducible. This tridimensional method yields statistically significant differences in measurements for right lung lobes when compared with planar scintigraphy. We recommend that SPECT/CT-based quantification be used for all lung cancer patients undergoing pretherapy evaluation of regional lung function.
Developmental Origins of Low Mathematics Performance and Normal Variation in Twins from 7 to 9 Years

Abstract A previous publication reported the etiology of mathematics performance in 7-year-old twins (Oliver et al., 2004). As part of the same longitudinal study we investigated low mathematics performance and normal variation in a representative United Kingdom sample of 1713 same-sex 9-year-old twins based on teacher-assessed National Curriculum standards. Univariate individual differences and DeFries-Fulker extremes analyses were performed. Similar to our results at 7 years, all mathematics scores at 9 years showed high heritability (.62–.75) and low shared environmental estimates (.00–.11) for both the low performance group and the full sample. Longitudinal analyses were performed from 7 to 9 years. These longitudinal analyses indicated strong genetic continuity from 7 to 9 years for both low performance and mathematics in the normal range. We conclude that, despite the considerable differences in mathematics curricula from 7 to 9 years, the same genetic effects largely operate at the two ages.
Examining Patterns of Exposure to Family Violence in Preschool Children: A Latent Class Approach.

Young children can experience violence directly or indirectly in the home, with some children exposed to multiple forms of violence. These polyvictims often experience violence that is severe, chronic, and multifaceted. The current study used latent class analysis to identify and examine the pattern of profiles of exposure to family violence (i.e., violence directed towards the child and between caregivers) among a sample of 474 children ages 3-6 year who were drawn from the Multidimensional Assessment of Preschoolers Study (Wakschlag et al., 2014). The data yielded 3 classes: a polyvictimized class (n = 72; 15.2%) with high probability of exposure to all forms of violence, a harsh parenting class (n = 235; 49.5%), distinguished mainly by child-directed physical discipline in the absence of more severe forms of violence, and a low-exposure class (n = 167; 35.2%). Classes were differentiated by contextual factors, maternal characteristics, and mother-reported and observational indicators of parenting and child functioning with most effect sizes between medium and large. These findings add to emerging evidence linking polyvictimization to impaired caregiving and adverse psychological outcomes for children and offer important insight for prevention and intervention for this vulnerable population.
A Novel Local Features Based Salient Object Recognition Algorithm via Hybrid SVM-QPSO Model

As the salient objects extraction is of great importance in computer vision and multimedia information retrieval, this paper concentrates on the problem of salient object recognition using local features. Considering the rotational invariance performance of circular region is much better, we exploit a circular region to replace the rectangular region. To implement the salient object detection, the visual object classes should be constructed from training image dataset through SIFT features clustering. Furthermore, for a test image, the object class which the test image belonged to can be detected by interest points matching. Afterwards, the SIFT features clustering and local features matching process can be implemented through the proposed hybrid SVM-QPSO model. To promote the quality of parameter selection in SVM, we utilize the quantum behaved particle swarm optimization technique to select suitable SVM parameters. Finally, experiments are conducted to make performance evaluation using the MSRC dataset. Experimental results show that compared with other methods, the proposed algorithm can effectively detect salient objects in both object detecting precision and computing efficiency.
Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis

BACKGROUND Sporothrix brasiliensis is the most virulent sporotrichosis agent. This species usually responds to antifungal drugs, but therapeutic failure can occur in some patients. Antifungal susceptibility tests have been performed on this species, but no clinical breakpoints (CBPs) are available. In this situation, minimal inhibitory concentration (MIC) distributions and epidemiological cutoff values (ECVs) support the detection of identification of resistant strains. OBJECTIVES To study the MIC distributions of five antifungal drugs against S. brasiliensis and to propose tentative ECVs. METHODS MICs of amphotericin B (AMB), itraconazole (ITR), ketoconazole (KET), posaconazole (POS), and terbinafine (TRB) against 335 S. brasiliensis strains were determined by the Clinical and Laboratory Standards Institute broth microdilution method. FINDINGS The proposed ECV, in µg/mL, for AMB, ITR, KET, POS, and TRB were 4.0, 2.0, 1.0, 2.0, and 0.25, respectively. Percentages of wild-type strains in our population for the above antifungal drugs were 98.48, 95.22, 95.33, 100, and 97.67%, respectively. MAIN CONCLUSIONS These ECVs will be useful to detect strains with resistance, to define CBPs, and to elaborate specific therapeutic guidelines for S. brasiliensis. Rational use of antifungals is strongly recommended to avoid the emergence of resistant strains and ensure the therapeutic effectiveness of sporotrichosis.
Load-sensitive rat gastric vagal afferents encode volume but not gastric nutrients

Mathis, Carole, Timothy H. Moran, and Gary J. Schwartz. Load-sensitive rat gastric vagal afferents encode volume but not gastric nutrients. Am. J. Physiol. 274 (Regulatory Integrative Comp. Physiol. 43): R280–R286, 1998. —To assess nutrient sensitivity in a population of gastric loadsensitive vagal afferents, their neurophysiological activity was examined in anesthetized rats with inflated pyloric cuffs after gastric infusion of a range of volumes of nutrient and equiosmotic saline solutions. Responses to physiological saline loads (1, 2, 4, and 8 ml) were compared with responses elicited by the same volume range of carbohydrate (12.5% glucose), protein (12.5% peptone), and equiosmotic hypertonic (750 mosM) saline. The threshold load volume of physiological saline required to increase gastric vagal afferent activity was 1 ml. Thereafter, there was a dose-dependent relationship between increasing gastric volume and firing rate and between gastric volume and pressure. The doseresponse relationships elicited by glucose, peptone, and equiosmotic hypertonic saline loads did not differ from those elicited by physiological saline loads. These data identify a population of gastric load-sensitive vagal afferents unresponsive to the chemical composition of gastric contents and are consistent with a role for vagal gastric volume signals but not gastric nutrient content in the negative feedback control of ingestion.
Fraternal Dropout

Recurrent neural networks (RNNs) are important class of architectures among neural networks useful for language modeling and sequential prediction. However, optimizing RNNs is known to be harder compared to feed-forward neural networks. A number of techniques have been proposed in literature to address this problem. In this paper we propose a simple technique called fraternal dropout that takes advantage of dropout to achieve this goal. Specifically, we propose to train two identical copies of an RNN (that share parameters) with different dropout masks while minimizing the difference between their (pre-softmax) predictions. In this way our regularization encourages the representations of RNNs to be invariant to dropout mask, thus being robust. We show that our regularization term is upper bounded by the expectation-linear dropout objective which has been shown to address the gap due to the difference between the train and inference phases of dropout. We evaluate our model and achieve state-of-the-art results in sequence modeling tasks on two benchmark datasets - Penn Treebank and Wikitext-2. We also show that our approach leads to performance improvement by a significant margin in image captioning (Microsoft COCO) and semi-supervised (CIFAR-10) tasks.
Prevalence and Hospital Discharge Status of Human Immunodeficiency Virus–Associated Pulmonary Arterial Hypertension in the United States

Pulmonary arterial hypertension (PAH) is a noninfectious complication of human immunodeficiency virus (HIV) infection that has gained in importance since the advent of antiretroviral therapy. HIV-associated PAH (HIV-PAH) has a higher prevalence than idiopathic PAH (IPAH), although the vascular pathology seen in HIV-PAH is virtually identical to that seen in IPAH. Initiating therapy for PAH at an early stage is associated with a better prognosis; however, because of the nonspecific symptoms associated with PAH, the diagnosis is often delayed. In addition, because of the low prevalence of HIV-PAH, routine screening for this condition has never been recommended. We hypothesize that the failure to create screening guidelines for HIV-PAH has resulted in underdiagnosis of the condition. This, in turn, results in individuals with HIV-PAH remaining undetected, allowing the disease to progress to more advanced stages or even remain unrecognized until death. If this hypothesis is correct, it may provide a strong argument for HIV-PAH screening guidelines, because HIV-PAH portends a poor prognosis and creates a significant economic burden if left untreated. To address this issue, we conducted a retrospective review of the National Hospital Discharge Survey data and the multiple-cause mortality data to determine the prevalence of HIV-PAH at hospital discharge and death. Using these large data sets, we observed that the prevalence of HIV-PAH among HIV-infected individuals at hospital discharge and death was significantly lower than the reported prevalence in the literature. In addition, we found that PAH was designated as the most common cause of mortality in patients with HIV-PAH.
Arginase activity is modulated by IL-4 and HOArg in nephritic glomeruli and mesangial cells.

Arginase shares a common substrate, l-arginine, with nitric oxide synthase (NOS). Both enzymes are active at inflammatory sites. To understand regulation of arginase and its relationship to nitric oxide (NO) production, we studied effects of N G-hydroxy-l-arginine (HOArg) and interleukin-4 (IL-4) on urea and[Formula: see text] synthesis by glomeruli during rat immune glomerulonephritis and compared these with macrophages and glomerular mesangial cells (MC). In nephritic glomeruli, elicited macrophages, and MC stimulated with IL-1 and adenosine 3',5'-cyclic monophosphate agonists, increased arginase and induced NOS activity was found. Urea production was inhibited by HOArg and increased by IL-4. NO inhibition [ N G-monomethyl-l-arginine (l-NMMA)] increased arginase activity in nephritic glomeruli and macrophages but not MC. [Formula: see text] synthesis was inhibited byl-NMMA and IL-4. It was increased with HOArg under conditions of NO inhibition. In contrast, in normal glomeruli and basal MC, where there was no induced NO synthesis, IL-4 had no effect on arginase activity, whereas HOArg consistently reduced it in glomeruli only. Type II arginase (Arg II) mRNA was detected in normal glomeruli; nephritic glomeruli expressed both Arg I and Arg II mRNAs. This is the first demonstration of arginase modulation in glomeruli and MC and of the expression of arginase isoforms in glomeruli. The differential responses to two endogenous compounds generated by inflammation suggest this may be part of coordinated regulation of arginase and inducible NOS in immune injury, whereby arginase is inhibited during high-output NO production and stimulated with NO suppression. This, together with control of arginase and NOS isoforms, may be important in controlling the balance of inflammatory and repair mechanisms.
The science of fake news

Addressing fake news requires a multidisciplinary effort The rise of fake news highlights the erosion of long-standing institutional bulwarks against misinformation in the internet age. Concern over the problem is global. However, much remains unknown regarding the vulnerabilities of individuals, institutions, and society to manipulations by malicious actors. A new system of safeguards is needed. Below, we discuss extant social and computer science research regarding belief in fake news and the mechanisms by which it spreads. Fake news has a long history, but we focus on unanswered scientific questions raised by the proliferation of its most recent, politically oriented incarnation. Beyond selected references in the text, suggested further reading can be found in the supplementary materials.
Stimulation of protein kinase C activity by tumor necrosis factor-α in bovine bronchial epithelial cells.

Bronchial epithelial cell migration, attachment, and proliferation are important processes in response to airway injury. We have shown that tumor necrosis factor (TNF)-α stimulates the migration of bovine bronchial epithelial cells (BBEC) in vitro. We hypothesized that protein kinase C (PKC) may be one of the intracellular signaling mediators of TNF-α in BBEC. In this study, we have identified multiple PKC isoforms in BBEC and measured total cellular PKC activity. Polyclonal antibodies to the PKC-α, -β2, -δ, and -ε isoforms recognized protein bands around 80-90 kDa. BBEC primary cultures treated with either 500 U/ml TNF-α for 2-4 h or 100 ng/ml 12- O-tetradecanoylphorbol 13-acetate for 15 min resulted in three- to fivefold increases in PKC activity in the particulate fractions of crude cell lysates. This activity was inhibited by 1 μM calphostin C or 10 μM H-7. Similarly, TNF-α-stimulated BBEC migration was reduced at least twofold in the presence of H-7 or calphostin C. These studies suggest that the activation of PKC is necessary for TNF-α-stimulated BBEC migration.
Effects of hyperthyroidism on vascular contractile and relaxation responses.

Previous research has shown that skeletal muscle blood flow, at rest and during muscular contractions, is elevated in the hyperthyroid state. We hypothesized that reduced vascular contractile and enhanced endothelium-dependent relaxation responses contribute to these observations. To test these hypotheses, male rats were administered triiodothyronine (Hyper, n = 27; 300 μg/kg) for 6-12 wk. Compared with euthyroid control rats (Eut, n = 27), Hyper exhibited left ventricular hypertrophy (Eut, 2.01 ± 0.04 mg/g body wt; Hyper, 2.70 ± 0.06; P < 0.0005) and greater oxidative enzyme activity in several skeletal muscles (all P < 0.0005). Vascular rings, 2-3 mm in axial length, were prepared from abdominal aortas, and responses to vasoactive agents were determined in vitro. Compared with Eut, vascular rings with intact endothelium from Hyper exhibited reductions in contractile responses to norepinephrine (NE) across a range of NE concentrations ( P < 0.05). Maximal tension developed in response to NE was reduced ∼30% in hyperthyroidism (Eut, 3.8 ± 0.2 g; Hyper, 2.6 ± 0.4; P < 0.01). Contractile responses to NE were not different between Eut and Hyper in rings denuded of endothelium. Maximal vasorelaxation responses to acetylcholine (ACh), after precontraction with NE (10-7 M), were enhanced in the hyperthyroid state (Eut, 65.1 ± 4.8%; Hyper, 84.0 ± 7.1; P < 0.05). Enhanced vasorelaxation to ACh was also observed when precontraction was induced by prostaglandin F2α. These findings indicate that vascular contractile and relaxation responses are altered in male hyperthyroid rats.