Miracle-dz/UniFAR-FTUs huggingface dataset:
Obstructive sleep apnoea, insulin resistance and sleepiness

Our understanding of obstructive sleep apnoea (OSA) has advanced much beyond that of the condition being a noisy breathing abnormality during sleep which classically presents with daytime sleepiness, to a condition with numerous potentially significant downstream sequelae and multisystem manifestations. The relationship between OSA and metabolic dysfunction is a moving target. Cross sectional studies have provided suggestive evidence for an independent relationship between OSA and adverse glucose metabolism, while supportive longitudinal data and interventional data from randomised controlled trials are still lacking.1 Recently, data from the Sleep Heart Health Study again confirmed the independent association between sleep disordered breathing and impaired glucose metabolism in normal weight and overweight/obese individuals.2 In this issue of Thorax , the study of Barcelo and colleagues3 suggested that the presence/absence of daytime sleepiness determined the presence/absence of increased insulin resistance in OSA, and that continuous positive airway pressure (CPAP) treatment decreased insulin resistance in sleepy subjects but had no effect in non-sleepy subjects (see page 946) . Their findings showed a pattern analogous to the previously reported phenomenon regarding OSA and elevated blood pressure, whereby the severity of daytime sleepiness in OSA predicted a blood pressure lowering response to CPAP treatment.4 5 Excessive daytime sleepiness has always been considered as one of the cardinal symptoms of OSA, and it is usually improved by effective treatment of OSA. However, it has also been well recognised that excessive daytime sleepiness is not universally present in OSA …
Nonlinearities of the Human Carotid Baroreceptor‐Cardiac Reflex

Carotid baroreceptors of nine healthy young men and women were stretched or compressed with neck suction or pressure, before and after β-adrenergic and cholinergic blockade, to evaluate several nonlinearities of sinus node baroreflex responses. Sinus node inhibition was related linearly to the intensity of brief baroreceptor stimuli over a range extending from carotid-distending pressures of about 101 ± 5 (mean ± SE) to 160 ± 6 mm Hg (the subjects' average systolic pressure was 108 ± 2 mm Hg). Sinus node responses to sustained (5 seconds) neck suction or pressure were strikingly asymmetrical. Responses were abolished by atropine, or by atropine and propranolol. Propranolol alone augmented sinus node responses to both neck suction and pressure. These results suggest that, in normal human subjects, sinus node responses to abrupt alterations of afferent baroreceptor traffic are nonlinear and are mediated by fluctuations of efferent cholinergic activity. Most of the observed nonlinear behavior of the integrated reflex can be explained on the basis of known properties of afferent and central portions of the baroreflex arc. Circ Res 47: 208-216, 1980
Are job and personal resources associated with work ability 10 years later? The mediating role of work engagement

Using a two-wave 10-year longitudinal design, this study examined the motivational process proposed by the Job Demands-Resources (JD-R) model. The aim was to examine whether work engagement acts as a mediator between job resources (i.e. supervisory relations, interpersonal relations and task resources) and personal resources (self-esteem) on the one hand and future work ability (i.e. a worker's functional ability to do their job) on the other. The second aim was to investigate the mediating role of engagement between past work ability and future work ability. Structural equation modelling was used to test the mediation hypotheses among Finnish firefighters (N = 403). As hypothesized, engagement at T2 fully mediated the impact of job and personal resources at T1 on work ability at T2. In addition, the effect of work ability at T1 on work ability at T2 was partially mediated by engagement at T2. These results indicate that job and personal resources may have long-term effects on engagement, and consequently on work ability, thus expanding on the propositions of the JD-R model. The results show a dual role of work ability, as a health-related resource that may foster engagement and an outcome driven by the motivational process proposed by the JD-R model.
Insulin‐Like Growth Factor‐I‐Enhanced Secretion Is Abolished in Protein Kinase C‐Deficient Chromaffin Cells

Abstract: Previous studies have demonstrated that bovine chromaffin cells cultured in medium with 10 nM insulin‐like growth factor‐I (IGF‐I) secrete about twofold more catecholamine when exposed to secretory stimuli than do cells cultured without IGF‐I. The purpose of this study was to determine whether protein kinase C (PKC) is involved in the effect of IGF‐I on secretion from these cells. PKC was down‐regulated in the cells by 16–18 h of treatment with β‐phorbol didecanoate (β‐PDD; 100 nM). Such treatment had no effect on high‐K+‐stimulated secretion from cells cultured without IGF‐I; however, secretion from cells cultured with IGF‐I was reduced to a level comparable to that in cells cultured without the peptide. The inactive isomer, α‐PDD (100 nM), had no effect on secretion from untreated or IGF‐I‐treated chromaffin cells. The effect of β‐PDD was time and concentration dependent, with 100 nM β‐PDD producing a maximal effect in 8–10 h. In situ PKC activity measured in permeabilized cells treated with PMA (300 nM) was decreased by∼40% by 10 h and was reduced to almost basal levels by 18 h. Immunoblotting experiments demonstrated that both α‐and ε‐PKC were lost from the cells with time courses similar to that seen in the in situ PKC assay. Overnight treatment with the PKC inhibitor H7 (100 μM) prevented the enhanced secretion normally seen in IGF‐l‐treated cells, whereas HA1004 had no effect. High‐K+‐stimulated 45Ca2+ uptake in IGF‐I‐treated cells was attenuated by long‐term treatment with β‐PDD (200 nM) or H7 (100 μM). Together these observations suggest that PKC is required for IGF‐I‐enhanced secretion from chromaffin cells.
Composition and integrity preservation of secure reactive systems

We consider compositional properties of reactive systems that are secure in a cryptographic sense. We follow the wellknown simulatability approach, i.e., the specification is an ideal system and a real system should in some sense simulate it. We recently presented the first detailed general definition of this concept for reactive systems that allows abstraction and enables proofs of efficient real-life systems like secure channels or certified mail. We prove two important properties of this definition, preservation of integrity and secure composition: First, a secure real system satisfies all integrity requirements (e.g., safety requirements expressed in temporal logic) that are satisfied by the ideal system. Secondly, if a composed system is designed using an ideal subsystem, it will remain secure if a secure real subsystem is used instead. Such a property was so far only known for non-reactive simulatability. Both properties are important for putting formal verification methods for systems using cryptography on a sound basis.
Identification of cis-Acting Elements and Splicing Factors Involved in the Regulation of BIM Pre-mRNA Splicing

Aberrant changes in the expression of the pro-apoptotic protein, BCL-2-like 11 (BIM), can result in either impaired or excessive apoptosis, which can contribute to tumorigenesis and degenerative disorders, respectively. Altering BIM pre-mRNA splicing is an attractive approach to modulate apoptosis because BIM activity is partly determined by the alternative splicing of exons 3 or 4, whereby exon 3-containing transcripts are not apoptotic. Here we identified several cis-acting elements and splicing factors involved in BIM alternative splicing, as a step to better understand the regulation of BIM expression. We analyzed a recently discovered 2,903-bp deletion polymorphism within BIM intron 2 that biased splicing towards exon 3, and which also impaired BIM-dependent apoptosis. We found that this region harbors multiple redundant cis-acting elements that repress exon 3 inclusion. Furthermore, we have isolated a 23-nt intronic splicing silencer at the 3′ end of the deletion that is important for excluding exon 3. We also show that PTBP1 and hnRNP C repress exon 3 inclusion, and that downregulation of PTBP1 inhibited BIM-mediated apoptosis. Collectively, these findings start building our understanding of the cis-acting elements and splicing factors that regulate BIM alternative splicing, and also suggest potential approaches to alter BIM splicing for therapeutic purposes.
Effect of PWM inverters on AC motor bearing currents and shaft voltages

This paper investigates AC induction motor shaft voltage problems, current flow through motor bearings and electric discharge current problems within bearings when operated under both pure sinewave and pulse width modulated (PWM) inverter sources. Experience suggests that PWM voltage sources with steep wavefronts especially increase the magnitude of the above electrical problems, leading to motor bearing material erosion and early mechanical failure. Previous literature suggests that shaft voltage-bearing current problems under 60 Hz sinewave operation are predominantly electromagnetically induced. It is proposed that under PWM operation these same problems are now predominantly an electrostatic phenomenon. A system model to describe this phenomenon is characterized and developed. Construction and test of a new electrostatic shielded induction motor (ESIM) verifies this model and is also a possible solution to the bearing current problem under PWM operation. <<ETX>>
Association between Social Capital and Self-Efficacy among Latinas in Nebraska

ABSTRACT Ensuring the health and well-being of Latinas is critical given the size of the population and its rapid growth across the United States. Social capital may be a tool for alleviating some of the individual, neighborhood, and societal challenges that Latina immigrants face. This study uses bivariate tests and multivariate regression to assess the association between social capital and self-efficacy among Latina immigrants in the Midwest (N = 94). Self-efficacy was positively correlated with bonding and bridging social capital. Findings from a multiple regression model indicate that bonding and bridging social capital are significantly associated with self-efficacy after adjusting for the effect of related covariates. Public health interventions may benefit from building and fostering bonding and bridging social capital among immigrants as way to improve self-efficacy, promote health, and enhance public health practice.
Reliable ℋ∞ filtering for LPV systems with sensor faults in finite frequency domain

This article deals with the reliable ℋ∞ filtering problem for linear parameter varying continuous-time systems with bounded disturbances and sensor faults. Different from existing approaches, a parameter-dependent filter is designed in finite frequency range, which is important in practice since full frequency approaches are conservative to some extent for the case when frequency ranges of disturbances are known beforehand. With the aid of Generalised Kalman–Yakubovich–Popov lemma, the filter design problem is formulated into solving a set of linear matrix inequalities problem. A numerical example is given to illustrate the effectiveness of the proposed methods.
Staying alive. Advancing medicinal chemistry by enhancing student responsibility for learning

Our Innovations in Teaching portfolio describes the most recent of our strategies to increase student interest in medicinal chemistry and in taking responsibility for learning. Course content was updated, rewritten and packaged in conversational packets containing a detailed lesson handout, learning objectives, lesson summary, and case study problems. Students read the handout packet and complete a comprehensive quiz over the material no later than 24 hours prior to class. Quiz questions are provided in the lesson packet to guide learning and the final quiz average counts for ten percent of the final grade, serving as the reward for preparedness. Lecturing over handout materials has been abandoned in favor of interactive discussion on areas of difficulty, active learning exercises and group presentations designed to stimulate analytical thinking and sharpen clinical problem solving skills. Students have been much better prepared for class discussion than in previous years, and responded positively to the quizzes and the interactive classroom. Performance, as measured by exam and final grades, did not suffer. This approach shows that small changes in content delivery, and the offering of relatively small academic rewards, can stimulate students to preparedness and enliven the classroom by allowing time for activities which foster higher level thinking and reinforce clinical relevance. In addition, interest in the subject matter is increased when classroom activities are more meaningful to the learners. Finally, professionalism will be optimized when the entire academic culture fosters student responsibility for learning.
Design and implementation of a fully-digital, high efficiency class-D amplifier system

Recent advances in semiconductor technology have renewed interest in class-D audio amplifiers, especially for portable devices and consumer electronics. The motivating factor driving research in class-D amplifiers is efficiency. In addition, one important benefit that class-D amplifiers bring is the ability to directly couple to a digital audio signal, removing the need to convert to analog first. In this paper, a FPGA-based digital audio amplifier has been developed, implemented and tested. The proposed class-D amplifier system can keep the audio signal chain in the digital domain, which prevents transmission noise from distorting the audio signal. In order to achieve the goals of high fidelity and high efficiency, a zero voltage switching (ZVS) modulation strategy is also presented. The experimental system demonstrates that fully digital audio amplification is possible. According to the experimental results, the proposed test system is able to deliver more than 15 W into a 4 Omega load with an efficiency of 80% and total harmonic distortion less than 2%.
Decorin enhances the proliferation and differentiation of myogenic cells through suppressing myostatin activity

Decorin, a small leucine‐rich proteoglycan, plays an important role in the regulation of cell growth. Our recent study has shown that immobilized decorin in the collagen matrix sequesters myostatin into the extracellular matrix and prevents its inhibitory action to myoblast proliferation in vitro. However, it still remains unclear whether free decorin could affect the proliferation and differentiation of myogenic cells by regulating myostatin activity. In the present study, we generated stable clonal C2C12 myoblasts that were over‐expressing decorin, and showed that decorin over‐expressing cells had an increased rate of proliferation as compared to control cells. Decorin over‐expressing cells formed multi‐giant hypertrophic myotubes with an elongated morphology and larger size as compared to control cells, although the initiation of differentiation in decorin over‐expressing cells was somewhat delayed as compared to control cells. Western blot analysis demonstrated that MyoD expression in decorin over‐expressing cells was lower than that in control cells until 12 h after induction to differentiate. At 48‐h differentiation, the expressions of MyoD, p21 and myogenin were dramatically increased in cells that over‐expressed decorin. Furthermore, we revealed that over‐expression of decorin suppressed the activity of myostatin endogenously synthesized in C2C12 myoblasts and attenuated the signaling of exogenous myostatin. Consistent with these results, knock‐down of decorin impairs C2C12 myoblast growth by increasing the sensitivity to exogenous myostatin. These results clearly show that decorin enhances the proliferation and differentiation of C2C12 myoblasts through suppressing myostatin activity. J. Cell. Physiol. 215: 856–867, 2008. © 2007 Wiley‐Liss, Inc.
The Promigratory Activity of the Matricellular Protein Galectin-3 Depends on the Activation of PI-3 Kinase

Expression of galectin-3 is associated with sarcoma progression, invasion and metastasis. Here we determined the role of extracellular galectin-3 on migration of sarcoma cells on laminin-111. Cell lines from methylcholanthrene-induced sarcomas from both wild type and galectin-3−/− mice were established. Despite the presence of similar levels of laminin-binding integrins on the cell surface, galectin-3−/− sarcoma cells were more adherent and less migratory than galectin-3+/+ sarcoma cells on laminin-111. When galectin-3 was transiently expressed in galectin-3−/− sarcoma cells, it inhibited cell adhesion and stimulated the migratory response to laminin in a carbohydrate-dependent manner. Extracellular galectin-3 led to the recruitment of SHP-2 phosphatase to focal adhesion plaques, followed by a decrease in the amount of phosphorylated FAK and phospho-paxillin in the lamellipodia of migrating cells. The promigratory activity of extracellular galectin-3 was inhibitable by wortmannin, implicating the activation of a PI-3 kinase dependent pathway in the galectin-3 triggered disruption of adhesion plaques, leading to sarcoma cell migration on laminin-111.
Closed-Loop Control of Grasping With a Myoelectric Hand Prosthesis: Which Are the Relevant Feedback Variables for Force Control?

In closed-loop control of grasping by hand prostheses, the feedback information sent to the user is usually the actual controlled variable, i.e., the grasp force. Although this choice is intuitive and logical, the force production is only the last step in the process of grasping. Therefore, this study evaluated the performance in controlling grasp strength using a hand prosthesis operated through a complete grasping sequence while varying the feedback variables (e.g., closing velocity, grasping force), which were provided to the user visually or through vibrotactile stimulation. The experiments were conducted on 13 volunteers who controlled the Otto Bock Sensor Hand Speed prosthesis. Results showed that vibrotactile patterns were able to replace the visual feedback. Interestingly, the experiments demonstrated that direct force feedback was not essential for the control of grasping force. The subjects were indeed able to control the grip strength, predictively, by estimating the grasping force from the prosthesis velocity of closing. Therefore, grasping without explicit force feedback is not completely blind, contrary to what is usually assumed. In our study we analyzed grasping with a specific prosthetic device, but the outcomes are also applicable for other devices, with one or more degrees-of-freedom. The necessary condition is that the electromyography (EMG) signal directly and proportionally controls the velocity/grasp force of the hand, which is a common approach among EMG controlled prosthetic devices. The results provide important indications on the design of closed-loop EMG controlled prosthetic systems.
Structure-function studies of two polysaccharide-degrading enzymes: Bacillus stearothermophilus α-amylase and Trichoderma reesei cellobiohydrolase II

Amylases and cellulases are important enzymes both for the global carbon cycle on earth and for biotechnical applications. They are capable of degrading polysaccharides, which are chemically simple polymers of repeating glucose units that form very complex and water-insoluble macroscopic structures. The enzymatic degradation of starch and cellulose is poorly understood at the molecular level. The cloning and DNA sequence determination of amylaseand cellulase-encoding genes from various organisms allows the use of modern techniques of molecular biology to study and alter their function. In the present investigation two different approaches were used to study the relationship between enzyme structure and function. In the first of these a random mutagenesis method developed in this study was applied. This method is applicable even without structural knowledge of a protein. The complete Bacillus stearothermophilus α-amylase gene was subjected to random mutagenesis, which was optimised to produce a single amino acid change at a time in the corresponding enzyme. Nearly 100 different mutant α-amylases were produced in an Escherichia coli host. The mutated enzymes had different activities on substrate plates used in screening. The location of the mutation(s) was analysed by sequencing the mutated gene. A molecular model of Bacillus stearothermophilus α-amylase was constructed on the basis of sequence alignment and the known structure of a fungal α-amylase from Aspergillus oryzae. The protein is expected to fold into three domains (A, B and C), like many other α-amylases. The data obtained from the analysis of the random mutants was compared to the constructed three-dimensional model. A reasonably good overall correlation was obtained between the mutant data and the model. Two areas on the α-amylase structural model were identified as being important for the activity on polymeric substrate: the open active site cleft situated between domains A and B and containing conserved amino acids known to be important for catalysis and multiple binding of glucose units in other α-amylases; and an interface between the catalytic domain A and domain C about 30 A away from the active site groove. The three-dimensional structure of Trichoderma reesei cellobiohydrolase II (CBHII) catalytic domain has been determined. The catalytic domain has an α/β barrel fold similar to that of the α-amylase catalytic domain A. Two stable surface loops generate a 20 A long tunnel for substrate binding and catalysis. The active site tunnel contains four defined binding sites (A-D) for glucosyl units. In the
Insulin Rescues Impaired Spermatogenesis via the Hypothalamic-Pituitary-Gonadal Axis in Akita Diabetic Mice and Restores Male Fertility

The mechanism responsible for poor reproductive outcomes in type 1 diabetic males is not well understood. In light of new evidence that the Sertoli cells of the testis secrete insulin, it is currently unclear whether diabetic subfertility is the result of deficiency of pancreatic insulin, testicular insulin, or both. In this study, the Akita mouse diabetic model, which expresses a mutant, nonfunctional form of ins2 in testes and pancreas, was used to distinguish between systemic and local effects of insulin deficiency on the process of spermatogenesis and fertility. We determined that Akita homozygous male mice are infertile and have reduced testis size and abnormal morphology. Spermatogonial germ cells are still present but are unable to mature into spermatocytes and spermatids. Exogenous insulin treatment regenerates testes and restores fertility, but this plasma insulin cannot pass through the blood-testis barrier. We conclude that insulin does not rescue fertility through direct interaction with the testis; instead, it restores function of the hypothalamic-pituitary-gonadal axis and, thus, normalizes hormone levels of luteinizing hormone and testosterone. Although we show that the Sertoli cells of the testis secrete insulin protein, this insulin does not appear to be critical for fertility.
Next Generation Group Facilitation

This article suggests that the effectiveness of group problem solving using facilitated processes appears to have reached an intellectual and methodological plateau. The time has come to move our thinking about group facilitation research and practice beyond this “plateau. ” Warfield's (1986) Domain of Science Model is seen as providing the appropriate frame from which to construct a new set of principles for group facilitation. These principles are set forth for designing an approach to facilitation of communication in problem-solving groups that is appropriate for dealing with the increasingly complex problems characteristic of today's organizations.