Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural Basis for the Interaction between Pectin Methylesterase and a Specific Inhibitor Protein

Pectin, one of the main components of the plant cell wall, is secreted in a highly methyl-esterified form and subsequently deesterified in muro by pectin methylesterases (PMEs). In many developmental processes, PMEs are regulated by either differential expression or posttranslational control by protein inhibitors (PMEIs). PMEIs are typically active against plant PMEs and ineffective against microbial enzymes. Here, we describe the three-dimensional structure of the complex between the most abundant PME isoform from tomato fruit (Lycopersicon esculentum) and PMEI from kiwi (Actinidia deliciosa) at 1.9-Å resolution. The enzyme folds into a right-handed parallel β-helical structure typical of pectic enzymes. The inhibitor is almost all helical, with four long α-helices aligned in an antiparallel manner in a classical up-and-down four-helical bundle. The two proteins form a stoichiometric 1:1 complex in which the inhibitor covers the shallow cleft of the enzyme where the putative active site is located. The four-helix bundle of the inhibitor packs roughly perpendicular to the main axis of the parallel β-helix of PME, and three helices of the bundle interact with the enzyme. The interaction interface displays a polar character, typical of nonobligate complexes formed by soluble proteins. The structure of the complex gives an insight into the specificity of the inhibitor toward plant PMEs and the mechanism of regulation of these enzymes.
Prenatal Exposure to Carbamazepine Reduces Hippocampal and Cortical Neuronal Cell Population in New-Born and Young Mice without Detectable Effects on Learning And Memory

Pregnant women with epilepsy have to balance maternal and fetal risks associated with uncontrolled seizures against the potential teratogenic effects from antiepileptic drugs (AEDs). Carbamazepine (CBZ) is among the four most commonly used AEDs for treatment of pregnant epileptic women. We previously reported that new-born children had a decreased head circumference after in utero CBZ exposure. This study investigates how prenatal exposure of CBZ influences the number of neurons in new-born and young mouse hippocampus, amygdala and cortex cerebri. Clinical studies describe inconclusive results on if prenatal CBZ treatment influences cognition. Here we investigate this issue in mice using two well characterized cognitive tasks, the passive avoidance test and the Morris water maze test. Prenatal exposure of CBZ reduced the number of neurons (NeuN-immunoreactive cells) in the new-born mouse hippocampus with 50% compared to non-exposed mice. A reduction of neurons (20%) in hippocampus was still observed when the animals were 5 weeks old. These mice also displayed a 25% reduction of neurons in cortex cerebri. Prenatal CBZ treatment did not significantly impair learning and memory measured in the passive avoidance test and in the Morris water maze. However, these mice displayed a higher degree of thigmotaxic behaviour than the control mice. The body weight of prenatally CBZ exposed five-week old mice were lower compared to control mice not exposed to CBZ (p = 0.001). In conclusion, prenatal exposure to CBZ reduces the number of neurons dramatically in areas important for cognition such as hippocampus and cortex, without severe impairments on learning and memory. These results are in line with some clinical studies, reporting that CBZ has minor negative effects on cognition. The challenge for future studies are to segment out what possible effects a reduction of neurons could have on different types of cognition, like intellectual ability and social interaction.
Probabilistic image segmentation with closedness constraints

We propose a novel graphical model for probabilistic image segmentation that contributes both to aspects of perceptual grouping in connection with image segmentation, and to globally optimal inference with higher-order graphical models. We represent image partitions in terms of cellular complexes in order to make the duality between connected regions and their contours explicit. This allows us to formulate a graphical model with higher-order factors that represent the requirement that all contours must be closed. The model induces a probability measure on the space of all partitions, concentrated on perceptually meaningful segmentations. We give a complete polyhedral characterization of the resulting global inference problem in terms of the multicut polytope and efficiently compute global optima by a cutting plane method. Competitive results for the Berkeley segmentation benchmark confirm the consistency of our approach.
Sense of meaning as a predictor of burnout in emergency physicians in Israel: a national survey

Objective Burnout is common in physicians and particularly acute in emergency physicians. Physician burnout may adversely affect physicians’ lives and the quality of care they provide, but much remains unknown about its main contributing factors. The present study evaluated burnout rates and contributing factors in emergency physicians in Israel, specifically focusing on the role of a sense of meaning, which has received little attention in the literature concerning burnout in emergency physicians. Methods A multicenter study, involving a convenience sample of physicians working full-time in the emergency departments of 16 general hospitals in Israel, was conducted. Questionnaires were used to assess burnout, demographic characteristics, professional stress, emotional distress, satisfaction, and quality of professional life, and open-ended questions were used to evaluate subjective perception of job satisfaction. Results Seventy physicians completed the questionnaires; 71.4% reported significant burnout levels in at least one of the burnout measures, while 82% also reported medium or high levels of competency. Burnout levels were associated with work-life balance, work satisfaction, social support, depressive symptoms, stress, and preoccupying thoughts. Regression analysis yielded two significant factors associated with burnout: worry and a sense of existential meaning derived from work. In addition, 61%, 51%, and 17% of participants exhibited high emotional exhaustion, high depersonalization, and a low sense of personal accomplishment, respectively. Conclusion These results indicate a high burnout rate in emergency physicians in Israel and highlight relevant positive and negative factors including the importance of addressing existential meaning in designing specific intervention programs to counter burnout.
Reduced Plasma Fibrin Clot Permeability and Susceptibility to Lysis in Patients with Inflammatory Bowel Disease: A Novel Prothrombotic Mechanism

Background:Inflammatory bowel disease (IBD) is associated with an increased risk of thromboembolism. Its mechanism is still unclear. Altered fibrin clot properties have been reported in patients with thromboembolism and those with chronic inflammatory states. We investigated whether fibrin characteristics are abnormal in IBD. Methods:Ex vivo plasma fibrin clot permeability (Ks), compaction, turbidity, and efficiency of fibrinolysis were assessed in 85 consecutive patients with IBD, including 47 with ulcerative colitis (UC) and 38 with Crohn's disease (CD), all with no history of thromboembolism. Forty-eight patients matched for age and sex served as controls. Results:Compared with controls, patients with UC and CD had 29.5% and 35.7% lower Ks associated with 13.8% and 23.1% lower compaction, respectively (all P < 0.001). Patients with UC and CD had higher maximum clot absorbance (+8.9%, P = 0.008, and +15.2%, P < 0.0001, respectively), higher maximum D-dimer released from clots (D-Dmax, +27.0%, P = 0.01, and +28.7%, P < 0.0001, respectively), and prolonged clot lysis time (+19.0%, P < 0.0001, and +25.5%, P < 0.0001, respectively). Lag phase was similar in both group of patients. D-Dmax was the only parameter that differed between patients in the UC and CD groups, being higher in CD (P = 0.04). The multiple linear regression model showed that in patients with UC, but not with CD, Ks, compaction, lysis time, and D-Dmax were all independently associated with disease activity. In patients with CD, Ks and lysis time were independently predicted by fibrinogen and C-reactive protein. Conclusions:Both UC and CD are characterized by formation of dense fibrin networks relatively resistant to lysis. Prothrombotic clot phenotype might represent a novel mechanism increasing thrombotic risk in IBD.
A Largely Deformable Surface Type Neural Electrode Array Based on PDMS

This paper describes a largely deformable surface type neural electrode array based on polydimethylsiloxane (PDMS) for cortical use. Noncracked and reliable metal patterns were fabricated successfully on PDMS substrate by employing an intermediate parylene layer. The mechanical and electrical stability of the fabricated electrode arrays was demonstrated by repeatable bending test using a custom-designed bending test module. Also the adhesion of the electrode structure consisting of PDMS, parylene and metal layers was proven by ASTM tape test. The electrode impedance was measured in phosphate buffered saline (PBS) solution at 37°C over three months and analyzed using equivalent circuit models. Based on these results, it is concluded that the suggested electrode array provides a largely deformable structure with mechanical integrity and electrical stability, which can withstand mechanical stresses when inserted through a small trephination hole in the skull and expanded in the small room between the cortex and the skull without damage to the electrode array.
NHLBI viewpoint: Lung health and disease prevention research starting in childhood

Lung health begins in utero when the complex structure of the airway, alveolar, and vascular structures are formed. To really impact the United States and global burden of chronic lung diseases in both adults and children, we must understand normal and abnormal development, the outcomes of disrupted development, and the effects of in utero and postnatal exposures on lung health. With increasing recognition of early life origins of adult diseases,1 it is important to know what early events and interventions can alter the trajectory of lung development, growth, and decline to help promote lung health and reduce chronic lung disease. Pediatr Pulmonol. 2015; 50:604–606. © 2015 Wiley Periodicals, Inc.
Novel molecular trends in the management of advanced non-small-cell lung cancer

In this article, we will summarize some of the aspects covered by key opinion leaders at the Perspectives in Lung Cancer Congress, particularly focusing on the most recent molecular discoveries in non-small-cell lung cancer which, we believe, will have a deep impact on the clinical development of novel targeted therapies in the future. We discuss genetic alterations in squamous cell carcinoma, crizotinib therapy for ALK-positive tumors, the latest information on antiangiogenic therapies, and strategies aimed at interfering with the Ras–Raf–MEK pathway in more detail. A special emphasis is placed on the potential implications that each covered point will have for the management of advanced non-small-cell lung cancer.
A Comparison of Neural Networks to Detect Failures in Micro-electro-mechanical Systems

The development of microelectronic industry has been related with the development of methodologies for detection of faults, either in production lines or in the field of action of devices. This has not happened in the industry of micro electromechanical systems (MEMS), which have made great progress in developing device but the fault detection techniques have been inherited the microelectronic. This presents a major problem since the nature of failures in MEMS is radically different from microelectronic failure. Given the complexity of fault modeling MEMS multi physics propose the use of neural networks as classifier system failures that could be implemented in systems self-test or verification in production line for these devices. Defective Comb Drive is detected by neural networks using as an input the resonance frequency and the gain.
Mobile phone-based interventions for smoking cessation

ABSTRACT BACKGROUND: Innovative effective smoking cessation interventions are required to appeal to those who are not accessing traditional cessation services. Mobile phones are widely used and are now well integrated into the daily lives of many, particularly young adults. Mobile phones are a potential medium for the delivery of health programmes such as smoking cessation. OBJECTIVES: To determine whether mobile phone-based interventions are effective at helping people who smoke, to quit. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Cinahl, PsycINFO, The Cochrane Library, the National Research Register and the ClinicalTrials register, with no restrictions placed on language or publication date. SELECTION CRITERIA: We included randomized or quasi-randomized trials. Participants were smokers of any age who wanted to quit. Studies were those examining any type of mobile phone-based intervention. This included any intervention aimed at mobile phone users, based around delivery via mobile phone, and using any functions or applications that can be used or sent via a mobile phone. DATA COLLECTION AND ANALYSIS: Information on the specified quality criteria and methodological details was extracted using a standardised form. Participants who dropped out of the trials or were lost to follow up were considered to be smoking. Meta-analysis of the included studies was undertaken using the Mantel-Haenszel Risk Ratio fixed-effect method provided that there was no evidence of substantial statistical heterogeneity as assessed by the I2 statistic. Where meta-analysis was not possible, summary and descriptive statistics are presented. MAIN RESULTS: Four studies were excluded as they were small non-randomized feasibility studies, and two studies were excluded because follow up was less than six months. Four trials (reported in five papers) are included: a text message programme in New Zealand; a text message programme in the UK; and an Internet and mobile phone programme involving two different groups in Norway. The different types of interventions are analysed separately. When combined by meta-analysis the text message programme trials showed a significant increase in short-term self-reported quitting (RR 2.18, 95% CI 1.80 to 2.65). However, there was considerable heterogeneity in long-term outcomes, with the much larger trial having problems with misclassification of outcomes; therefore these data were not combined. When the data from the Internet and mobile phone programmes were pooled we found statistically significant increases in both short and long-term self-reported quitting (RR 2.03, 95% CI 1.40 to 2.94). AUTHORS’ CONCLUSIONS: The current evidence shows no effect of mobile phone-based smoking cessation interventions on long-term outcome. While short-term results are positive, more rigorous studies of the long-term effects of mobile phone-based smoking cessation interventions are needed.
A Creative Improvisational Companion Based on Idiomatic Harmonic Bricks

We describe an improvisational companion based on the concept of harmonic bricks, as articulated by Cork and others. Our companion is software that can play background for, and trade melodies with, a human soloist. While exhibiting creativity itself, its greater purpose is to improve creativity of its user. Bricks, originally intended for memorization of chord progressions, are used here as a structuring device for improvised melodies within a tune, as a basis for interaction, and as a means of learning new grammars for the purpose of generating melodies by the companion. A user interface for a partially implemented system is presented.
RobuSTore: Robust Performance for Distributed Storage Systems

Emerging large-scale scientific applications involve massive, distributed, shared data collections in petabytes, and require robust, high performance for read-dominated workloads. Achieving robust performance, i.e. low variability, in storage systems is difficult. We propose RobuSTore, a novel storage technique, which combines erasure codes and speculative access to reduce performance variability and increase performance. RobuSTore uses erasure codes to add flexible redundancy then spreads the encoded data across a large number of disks. Speculative access to the redundant data from multiple disks enables application requests to be satisfied with only early-arriving blocks, reducing performance dependence on the behavior of individual disks. We present the design and an evaluation of RobuSTore which shows improved robustness, reducing the standard deviation of access latencies by as much as 5-fold vs. traditional RAID. In addition, RobuSTore improves access bandwidth by as much as 15-fold. RobuSTore secures these benefits at the cost of a 2-3x storage capacity overhead and ~1.5x network and disk I/O overhead.
Structure and function of small arteries.

The small arteries (prearteriolar vessels with lumen diameter less than approximately 500 microns) contribute importantly to and participate actively in the regulation of the peripheral resistance. New techniques, building on the classic histological and hemodynamic techniques, have enabled detailed in vitro investigation of small arteries. At present, research in small arteries is in its infancy, and our understanding of the heterogeneity of small arteries within vascular beds, between vascular beds, and between species is extremely limited. This review attempts to describe the current status of the field. New techniques, based primarily on a wire myograph (where the vessels are mounted as ring preparations) and a pressure myograph (where vessels are cannulated and pressure-lumen relations are determined), have allowed in vitro investigations of small arteries. The more physiological arrangement of the pressure myograph allows, for example, investigation of the vasoconstrictor response to raised intravascular pressure (the Bayliss response), whereas the less-sophisticated wire myograph is similar to use and may be more useful in certain situations where particular mechanisms are being investigated. Both techniques allow simultaneous measurements of vessel tone and a variety of parameters (e.g., membrane potential and intracellular ion activities) and thus allow precise determination of the relation between small artery structure and function. The vessels appear to remain fully viable with regard to the contractility of their smooth muscle cells as well as to the function of their perivascular nerves and their endothelium. The evidence suggests that the monovalent transport mechanisms in the plasma membrane, in particular potassium channels, play an important role in the determination of the membrane potential in small arteries, although the relation is more complex than indicated by the Goldman equation. Confirmation of these findings requires, however, simultaneous determinations of ion transport and vascular tone under conditions where vessels are subjected to mechanical loading. The membrane potential, through its effect on potential-dependent calcium channels, plays an important role in the determination of vascular tone. With regard to calcium homeostasis, current knowledge is hampered by the lack of direct measurements of the relation between cytoplasmic calcium and vascular tone. The evidence, however, suggests that besides potential-dependent calcium channels, receptor-operated calcium channels are present in the plasma membrane, although this still requires confirmation. The role of the sarcoplasmic reticulum is not clarified. (ABSTRACT TRUNCATED AT 400 WORDS)
The Gifted Side of Autism

I sat rocking in bed as isolated pieces of information that I had received throughout my life suddenly came together. As an infant and toddler, I rocked, both sitting and on hands and knees, for long periods of time. I squirmed when my mother tried to hold me. I erupted frequently with horrific temper tantrums, especially at meals and bedtime, screaming long and loud, kicking, scratching my face, pulling my hair, banging my head, and holding my breath until I turned blue. My brother told me, &dquo;We couldn’t figure out where the off-switch was. &dquo; My cousin (who always couches what she says as gently as possible) told me, &dquo;You showed at an early age that you had a will of your own. &dquo; Because I was no longer acting that badly at age 50, I assumed I could not
DRESS down: /ɛ/-lowering in apparent time in a rural Scottish community

This paper presents a sociophonetic investigation of /ɛ/-lowering in apparent time. The data come from 24 speakers, across three generations from Buckie, northeast Scotland (12 males, 12 females). Acoustic analysis of the DRESS-vowel reveals that it is lowering in apparent time. Inspection of the constraints reveals an interaction of internal and external constraints. Analysis of the phonetic context revealed that following-l promoted DRESS lowering. However, this conditioning was only significant for the young females who were shown to be leading the change. The results presented here are related to broader phonological characteristics of the Buckie dialect as well as ongoing changes in a number of different English varieties
The Experience of Outdoor Education at Operation Purple® Camp

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Fas‐mediated hepatocyte apoptosis is increased by hepatitis C virus infection and alcohol consumption, and may be associated with hepatic fibrosis: mechanisms of liver cell injury in chronic hepatitis C virus infection

Epidemiological studies have established that heavy alcohol consumption in persons with chronic hepatitis C virus (HCV) infection is associated with advanced liver disease, including cirrhosis. The aims of this study were to evaluate the relationship between alcohol consumption and hepatocyte apoptosis in HCV‐infected patients and to determine the role of Fas in HCV‐mediated apoptosis. Liver tissue from 44 HCV‐infected patients with variable alcohol consumption, and 10 normal control subjects who did not consume alcohol was examined for hepatocyte apoptosis, proliferation and Fas expression. Alcohol consumption was assessed using the ‘Lifetime Drinking History’ alcohol questionnaire. HCV RNA, alanine aminotransferase (ALT) and ferritin were also assessed in addition to demographic data. Hepatocyte apoptosis was significantly greater in HCV‐infected patients compared to controls. Expression of Fas (CD95) was found in HCV patients but not in controls. The degree of Fas expression correlated with hepatocyte apoptosis as detected by terminal UTP nick end labelling (TUNEL). Active ethanol consumption led to a significant increase in hepatocyte apoptosis. Fas expression correlated with fibrosis in HCV‐infected patients who were not actively drinking ethanol. In summary, HCV leads to increased apoptotic cell death in hepatocytes. Programmed cell death can be further up‐regulated by active ethanol consumption. The correlation between Fas expression and TUNEL supports the hypothesis that the Fas–Fas ligand interaction is the major mechanism for HCV‐induced hepatocyte apoptosis.