Miracle-dz/UniFAR-FTUs huggingface dataset:
Complex regulation controls Neurogenin3 proteolysis

Summary The ubiquitin proteasome system (UPS) is known to be responsible for the rapid turnover of many transcription factors, where half-life is held to be critical for regulation of transcriptional activity. However, the stability of key transcriptional regulators of development is often very poorly characterised. Neurogenin 3 (Ngn3) is a basic helix–loop–helix transcription factor that plays a central role in specification and differentiation of endocrine cells of the pancreas and gut, as well as spermatogonia and regions of the brain. Here we demonstrate that Ngn3 protein stability is regulated by the ubiquitin proteasome system and that Ngn3 can be ubiquitylated on lysines, the N-terminus and, highly unusually, on non-canonical residues including cysteines and serines/threonines. Rapid turnover of Ngn3 is regulated both by binding to its heterodimeric partner E protein and by the presence of cdk inhibitors. We show that protein half-life does appear to regulate the activity of Ngn3 in vivo, but, unlike the related transcription factor c-myc, ubiquitylation on canonical sites is not a requirement for transcriptional activity of Ngn3. Hence, we characterise an important new level of Ngn3 post-translational control, which may regulate its transcriptional activity.
Sequential pattern mining from trajectory data

In this paper, we study the problem of mining for frequent trajectories, which is crucial in many application scenarios, such as vehicle traffic management, hand-off in cellular networks, supply chain management. We approach this problem as that of mining for frequent sequential patterns. Our approach consists of a partitioning strategy for incoming streams of trajectories in order to reduce the trajectory size and represent trajectories as strings. We mine frequent trajectories using a sliding windows approach combined with a counting algorithm that allows us to promptly update the frequency of patterns. In order to make counting really efficient, we represent frequent trajectories by prime numbers, whereby the Chinese reminder theorem can then be used to expedite the computation.
Isolated Diastolic Hypotension and Incident Heart Failure in Older Adults

Aging is often associated with increased systolic blood pressure and decreased diastolic blood pressure. Isolated systolic hypertension or an elevated systolic blood pressure without an elevated diastolic blood pressure is a known risk factor for incident heart failure in older adults. In the current study, we examined whether isolated diastolic hypotension, defined as a diastolic blood pressure <60 mm Hg and a systolic blood pressure ≥100 mm Hg, is associated with incident heart failure. Of the 5795 Medicare-eligible community-dwelling adults age ≥65 years in the Cardiovascular Health Study, 5521 were free of prevalent heart failure at baseline. After excluding 145 individuals with baseline systolic blood pressure <100 mm Hg, the final sample included 5376 participants, of whom 751 (14%) had isolated diastolic hypotension. Propensity scores for isolated diastolic hypotension were calculated for each of the 5376 participants and used to match 545 and 2348 participants with and without isolated diastolic hypotension, respectively, who were balanced on 58 baseline characteristics. During >12 years of median follow-up, centrally adjudicated incident heart failure developed in 25% and 20% of matched participants with and without isolated diastolic hypotension, respectively (hazard ratio associated with isolated diastolic hypotension: 1.33 [95% CI: 1.10–1.61]; P=0.004). Among the 5376 prematch individuals, multivariable-adjusted hazard ratio for incident heart failure associated with isolated diastolic hypotension was 1.29 (95% CI: 1.09–1.53; P=0.003). As in isolated systolic hypertension, among community-dwelling older adults without prevalent heart failure, isolated diastolic hypotension is also a significant independent risk factor for incident heart failure.
Conformational stability and multistate unfolding of poly(A)‐specific ribonuclease

Poly(A)‐specific ribonuclease (PARN) specifically catalyzes the degradation of the poly(A) tails of single‐stranded mRNAs in a highly processive mode. PARN participates in diverse and important intracellular processes by acting as a regulator of mRNA stability and translational efficiency. In this article, the equilibrium unfolding of PARN was studied using both guanidine hydrochloride and urea as chemical denaturants. The unfolding of PARN was characterized as a multistate process, but involving dissimilar equilibrium intermediates when denatured by the two denaturants. A comparison of the spectral characteristics of these intermediates indicated that the conformational changes at low concentrations of the chemical denaturants were more likely to be rearrangements of the tertiary and quaternary structures. In particular, an inactive molten globule‐like intermediate was identified to exist as soluble non‐native oligomers, and the formation of the oligomers was modulated by electrostatic interactions. An active dimeric intermediate unique to urea‐induced unfolding was characterized to have increased regular secondary structures and modified tertiary structures, implying that additional regular structures could be induced by environmental stresses. The dissimilarity in the unfolding pathways induced by guanidine hydrochloride and urea suggest that electrostatic interactions play an important role in PARN stability and regulation. The appearance of multiple intermediates with distinct properties provides the structural basis for the multilevel regulation of PARN by conformational changes.
Angiotensin-converting enzyme gene insertion/deletion polymorphism in Egyptian patients with myocardial infarction

Introduction. This work aimed to test the association of the angiotensin-converting enzyme gene insertion/deletion (I/D) polymorphism with myocardial infarction. Subjects and methods. This study comprised 79 Egyptian myocardial infarction cases with a mean age of 54.4±9.9 years including 60 males and 19 females, plus 238 healthy unrelated individuals of nearly matched age and sex as a control group. For all subjects, DNA testing for the angiotensin-converting enzyme gene I/D polymorphism was done using PCR amplification for detection of both the D and I alleles followed by a second run PCR specific for the I allele for samples typed as DD in the first run. Results. Cases had a higher frequency of DD (29.1%) and ID (62.0%) genotypes than II (8.9%) genotype, with a higher frequency of D allele than I allele (64.4% vs. 33.6%). Compared to controls, cases had a significantly higher frequency of ID genotype (62.0% vs. 47.5%, p<0.05). This was more apparent among cases in the low risk group (p=0.002) than in the high risk group (p=0.041). Conclusion. The angiotensin-converting enzyme gene I/D polymorphism is probably a risk factor for ischaemic heart disease among Egyptian cases, particularly if integrated with other environmental and genetic risk factors.
Nociceptor Sensitization by Extracellular Signal-Regulated Kinases

Inflammatory pain, characterized by a decrease in mechanical nociceptive threshold (hyperalgesia), arises through actions of inflammatory mediators, many of which sensitize primary afferent nociceptors via G-protein-coupled receptors. Two signaling pathways, one involving protein kinase A (PKA) and one involving the epsilon isozyme of protein kinase C (PKCε), have been implicated in primary afferent nociceptor sensitization. Here we describe a third, independent pathway that involves activation of extracellular signal-regulated kinases (ERKs) 1 and 2. Epinephrine, which induces hyperalgesia by direct action at β2-adrenergic receptors on primary afferent nociceptors, stimulated phosphorylation of ERK1/2 in cultured rat dorsal root ganglion cells. This was inhibited by a β2-adrenergic receptor blocker and by an inhibitor of mitogen and extracellular signal-regulated kinase kinase (MEK), which phosphorylates and activates ERK1/2. Inhibitors of Gi/o-proteins, Ras farnesyltransferases, and MEK decreased epinephrine-induced hyper-algesia. In a similar manner, phosphorylation of ERK1/2 was also decreased by these inhibitors. Local injection of dominant active MEK produced hyperalgesia that was unaffected by PKA or PKCε inhibitors. Conversely, hyperalgesia produced by agents that activate PKA or PKCε was unaffected by MEK inhibitors. We conclude that a Ras–MEK–ERK1/2 cascade acts independent of PKA or PKCε as a novel signaling pathway for the production of inflammatory pain. This pathway may present a target for a new class of analgesic agents.
Food Allergy Diagnosis and Management Practices Among Pediatricians

Our goals were to (1) estimate the rates of parent-reported versus physician-diagnosed food allergy, (2) determine pediatrician adherence to national guidelines, and (3) obtain pediatricians’ perspectives on guideline nonadherence. A mixed method approach was used, including survey, chart review, and qualitative methods. Overall, 10.9% of parents reported having a child with food allergy and two thirds of these cases were detected by the pediatrician. Chart reviews revealed high rates of guideline adherence with respect to allergist referral (67.3%), but less consistent adherence regarding documentation of reaction history (38.8%), appropriate use of diagnostic tests (34.7%), prescription of epinephrine autoinjectors (44.9%), and counseling families in food allergy management (24.5%). Pediatricians suggested that poor adherence was due to lack of documentation, familiarity with guidelines, and clarity regarding the pediatrician’s role in managing food allergy. Findings emphasize the need to better establish the role of the pediatrician and to improve awareness and adherence to guidelines.
Detection of Lipid-Core Plaques by Intracoronary Near-Infrared Spectroscopy Identifies High Risk of Periprocedural Myocardial Infarction

Background— Percutaneous coronary intervention (PCI) is associated with periprocedural myocardial infarction (MI) in 3% to 15% of cases (depending on the definition used). In many cases, these MIs result from distal embolization of lipid-core plaque (LCP) constituents. Prospective identification of LCP with catheter-based near-infrared spectroscopy (NIRS) may predict an increased risk of periprocedural MI and facilitate development of preventive measures. Methods and Results— The present study analyzed the relationship between the presence of a large LCP (detected by NIRS) and periprocedural MI. Patients with stable preprocedural cardiac biomarkers undergoing stenting were identified from the COLOR Registry, an ongoing prospective observational study of patients undergoing NIRS before PCI. The extent of LCP in the treatment zone was calculated as the maximal lipid-core burden index (LCBI) measured by NIRS for each of the 4-mm longitudinal segments in the treatment zone. A periprocedural MI was defined as new cardiac biomarker elevation above 3× upper limit of normal. A total of 62 patients undergoing stenting met eligibility criteria. A large LCP (defined as a maxLCBI4 mm ≥500) was present in 14 of 62 lesions (22.6%), and periprocedural MI was documented in 9 of 62 (14.5%) of cases. Periprocedural MI occurred in 7 of 14 patients (50%) with a maxLCBI4 mm ≥500, compared with 2 of 48 patients (4.2%) patients with a lower maxLCBI4 mm (P=0.0002). Conclusions— NIRS provides rapid, automated detection of extensive LCPs that are associated with a high risk of periprocedural MI, presumably due to embolization of plaque contents during coronary intervention.
Vacuum static compactified wormholes in eight-dimensional Lovelock theory

In this paper, new exact solutions in eight-dimensional Lovelock theory will be presented. These solutions are the vacuum static wormhole, the black hole, and generalized Bertotti-Robinson space-times with nontrivial torsion. All of the solutions have a cross product structure of the type M{sub 5}x{sigma}{sub 3}, where M{sub 5} is a five-dimensional manifold and {sigma}{sub 3} a compact constant curvature manifold. The wormhole is the first example of a smooth vacuum static Lovelock wormhole which is neither Chern-Simons nor Born-Infeld. It will be also discussed how the presence of torsion affects the 'navigableness' of the wormhole for scalar and spinning particles. It will be shown that the wormhole with torsion may act as 'geometrical filter': A very large torsion may 'increase the traversability' for scalars while acting as a 'polarizator' on spinning particles. This may have interesting phenomenological consequences.
Bronchodilator treatment in moderate asthma or chronic bronchitis: continuous or on demand? A randomised controlled study.

OBJECTIVE--To examine the effect of bronchodilator treatment given continuously versus on demand on the progression of asthma and chronic bronchitis and to compare the long term effects of a beta 2 adrenergic drug (salbutamol) and an anticholinergic drug (ipratropium bromide). DESIGN--Two year randomised controlled prospective 'crossover' study in which patients were assigned to one of two parallel treatment groups receiving continuous treatment or treatment on demand. SETTING--29 general practices in the catchment area of the University of Nijmegen. PATIENTS--223 patients aged greater than or equal to 30 with moderate airway obstruction due to asthma or chronic bronchitis, selected by their general practitioners. INTERVENTIONS--1600 micrograms salbutamol or 160 micrograms ipratropium bromide daily (113 patients) or salbutamol or ipratropium bromide only during exacerbations or periods of dyspnoea (110). No other pulmonary treatment was permitted. MAIN OUTCOME MEASURES--Decline in ventilatory function and change in bronchial responsiveness, respiratory symptoms, number of exacerbations, and quality of life. RESULTS--Among 144 patients completing the study, after correction for possible confounding factors the decline in forced expiratory volume in one second was -0.072 l/year in continuously treated patients and -0.020 l/year in those treated on demand (p less than 0.05), irrespective of the drug. The difference in the decline in patients with asthma was comparable with that in patients with chronic bronchitis (asthma: 0.092 v -0.025 l/year; chronic bronchitis: -0.082 v -0.031 l/year). Bronchial responsiveness increased slightly (0.4 doubling dose) with continuous treatment in chronic bronchitis, but exacerbations, symptoms, and quality of life were unchanged. Salbutamol and ipratropium bromide had comparable effects on all variables investigated. CONCLUSIONS--Continuous bronchodilator treatment without anti-inflammatory treatment accelerates decline in ventilatory function. Bronchodilators should be used only on demand, with additional corticosteroid treatment, if necessary.
Durability of E-Glass/Vinylester Reinforcement in Alkaline Solution

This paper presents results from a 9-month experimental study to evaluate the durability of E-glass/vinylester reinforcement used by the U.S. Navy in the construction of the MRI Pier in San Diego, California. A total of 36 specimens were tested. These were split into 4 groups of 9 specimens each exposed to simulated pore solution with a pH ranging from 13.3 to 13.5 for periods of 1, 3, 6, and 9 months. Of the 9 specimens in each group, 33% were unstressed, 33% were stressed to 10%, and the remaining 33% were stressed to either 15 or 25% of their ultimate short-term tensile strength. At the end of the exposure periods, surviving specimens were tested to failure to determine their residual tensile strength. Results showed that the E-glass/vinylester bars tested had very limited durability in this environment, especially at stress levels of 15% or higher. Overall, findings indicate that first-generation glass fiber-reinforced polymer bars are unsuitable as structural reinforcement in concrete members.
Phenotypes and Genotypes of Erythromycin-Resistant Pneumococci in Italy

ABSTRACT Of 120 erythromycin-resistant pneumococci isolated in Italian hospitals, 39 (32.5%) were M-type isolates, carrying the mef gene alone. The mef gene was also detected, together with erm(AM), in one constitutively resistant isolate and in five isolates of the partially inducible phenotype. Among the 45 mef-positive isolates, 25 (55.6%) carried mef(A) and 20 (44.4%) carried mef(E) as observed from PCR-restriction fragment length polymorphism analysis of a 1,743-bp amplicon. The same result was obtained by a similar method applied to a more common 348-bp amplicon.
Limit Loads for Pipe Elbows Subjected to In-Plane Opening Moments and Internal Pressure

The purpose of this study is to determine limit loads for pipe elbows subjected to in-plane bending moments that tend to open the elbow (i.e., increase its radius of curvature), and the influence of internal pressure on the value of the limit load. Load-deflection curves were obtained, and from these curves plastic collapse and instability loads at various values of internal pressure were determined. This was done for different pipe bend factors (h = Rt/r 2 ) using the nonlinear finite element analysis code (ABAQUS) with its special elbow element. A set of limit curves was generated from the results. These curves show the variation of collapse and instability loads with internal pressure for different elbows. Collapse loads were found to increase and then decrease with increasing pressure for all the elbow geometries studied. Instability loads were difficult to reach because of the large stiffening effect of the elbow cross-sectional deformation, and they were generally found to decrease with increasing pressure.
Unsupervised Human Action Detection by Action Matching

We propose a new task of unsupervised action detection by action matching. Given two long videos, the objective is to temporally detect all pairs of matching video segments. A pair of video segments are matched if they share the same human action. The task is category independent—it does not matter what action is being performed—and no supervision is used to discover such video segments. Unsupervised action detection by action matching allows us to align videos in a meaningful manner. As such, it can be used to discover new action categories or as an action proposal technique within, say, an action detection pipeline. Moreover, it is a useful pre-processing step for generating video highlights, e.g., from sports videos. ,,,,,, We present an effective and efficient method for unsupervised action detection. We use an unsupervised temporal encoding method and exploit the temporal consistency in human actions to obtain candidate action segments. We evaluate our method on this challenging task using three activity recognition benchmarks, namely, the MPII Cooking activities dataset, the THUMOS15 action detection benchmark and a new dataset called the IKEA dataset. On the MPII Cooking dataset we detect action segments with a precision of 21.6% and recall of 11.7% over 946 long video pairs and over 5000 ground truth action segments. Similarly, on THUMOS dataset we obtain 18.4% precision and 25.1% recall over 5094 ground truth action segment pairs.
Optimal detection of fetal chromosomal abnormalities by massively parallel DNA sequencing of cell-free fetal DNA from maternal blood.

BACKGROUND Massively parallel DNA sequencing of cell-free fetal DNA from maternal blood can detect fetal chromosomal abnormalities. Although existing algorithms focus on the detection of fetal trisomy 21 (T21), these same algorithms have difficulty detecting trisomy 18 (T18). METHODS Blood samples were collected from 1014 patients at 13 US clinic locations before they underwent an invasive prenatal procedure. All samples were processed to plasma, and the DNA extracted from 119 samples underwent massively parallel DNA sequencing. Fifty-three sequenced samples came from women with an abnormal fetal karyotype. To minimize the intra- and interrun sequencing variation, we developed an optimized algorithm by using normalized chromosome values (NCVs) from the sequencing data on a training set of 71 samples with 26 abnormal karyotypes. The classification process was then evaluated on an independent test set of 48 samples with 27 abnormal karyotypes. RESULTS Mapped sites for chromosomes of interest in the sequencing data from the training set were normalized individually by calculating the ratio of the number of sites on the specified chromosome to the number of sites observed on an optimized normalizing chromosome (or chromosome set). Threshold values for trisomy or sex chromosome classification were then established for all chromosomes of interest, and a classification schema was defined. Sequencing of the independent test set led to 100% correct classification of T21 (13 of 13) and T18 (8 of 8) samples. Other chromosomal abnormalities were also identified. CONCLUSION Massively parallel sequencing is capable of detecting multiple fetal chromosomal abnormalities from maternal plasma when an optimized algorithm is used.
Origin of negative potentials in the light-adapted ERG of cat retina.

1. The light-adapted diffuse-flash electroretinogram (ERG) in the cat exhibits two prominent negative components: a sustained negative potential during illumination and a negative-going OFF response. We investigated their intraretinal origins and found that the sustained component originates from the rod photoreceptors, whereas the OFF response represents a combination of the return to base line of the rod-receptor potential, the offset of PII (rod and cone), and a cone-dependent OFF response originating proximal to the photoreceptors at very high background levels. 2. The ERG, evoked in response to diffuse illumination of the light- and dark-adapted cat retina, was recorded between a chlorided silver wire in the vitreous and a plate behind the eye. Extracellular field potentials were recorded simultaneously with a microelectrode placed intraretinally at different retinal depths. 3. The sustained negative potential and the negative OFF response were not the M-wave ON and OFF responses of proximal retina, despite an overall resemblance in form and time course: 1) the M-wave was spatially tuned, whereas the ERG components were not; 2) tetrodotoxin (TTX) (3.8-microM vitreal concentration) did not alter the M-wave, but it reduced the ERG OFF response; 3) picrotoxin (0.14 mM, after TTX) enhanced the M-wave but did not affect the negative ERG; and 4) 2-amino-4-phosphonobutyric acid (APB; 0.95 mM) removed the M-wave ON response, and aspartate (43 mM) removed the M-wave OFF response, in addition, while the sustained negative potential persisted. 4. The sustained negative potential was not slow PIII, the neural retinal component of the c-wave, a Müller cell response to the photoreceptor-dependent light-evoked decrease in subretinal extracellular K+ concentration [( K+]o). Although Ba2+ (repeated injections of 4-5 mM), a K+ conductance blocker, eliminated slow PIII, it did not remove the sustained negative potential. We concluded that the sustained negative potential was a photoreceptor potential, and the spectral sensitivity of the response indicated that it arose from rods. 5. The contribution of the rod-receptor potential to the ERG depended on background illumination. It was a sustained potential for a range of backgrounds near and 1 or 2 log units above the illumination that saturates rod-driven responses in cat (8.2 log quanta.deg-2.s-1). At lower background intensities, it appeared only as a dip between the b- and c-waves, the b-wave trough, which also was present in fully dark-adapted responses. (ABSTRACT TRUNCATED AT 400 WORDS)