Miracle-dz/UniFAR-FTUs huggingface dataset:
Perindopril chronically inhibits angiotensin-converting enzyme in both the endothelium and adventitia of the internal mammary artery in patients with ischemic heart disease.

BACKGROUND ACE inhibitors are widely used in treating hypertension and heart failure, but the sites and mechanisms of ACE inhibition in human blood vessels are not understood. The present study was undertaken to assess the sites and extent of in vivo inhibition of ACE by long-term perindopril treatment in different layers of the internal mammary artery in patients with ischemic heart disease. METHODS AND RESULTS Sixteen patients with ischemic heart disease were treated either with perindopril (4 mg/d PO) for up to 36 days before surgery (n = 9) or without the inhibitor as control subjects (n = 7). The segments of the internal mammary artery were collected for measurement of vascular free and total ACE by quantitative in vitro autoradiography with 125I-351A binding. The patients treated with perindopril had lower plasma ACE (P < .001) and plasma angiotensin (Ang) II-to-Ang I ratio (P < .05). In the internal mammary artery, free ACE was similarly inhibited by perindopril in the endothelium (P < .05) and adventitia (P < .05), and the free ACE-to-total ACE ratio, an index of ACE inhibition, was markedly decreased by perindopril in parallel in the endothelium (P < .001) and adventitia (P < .001). Moreover, plasma ACE correlated highly with vascular ACE in the endothelium (r = .85, P < .001) or adventitia (r = .78, P < .001), and mean arterial pressure correlated significantly with free ACE in the endothelium (r = .52, P < .05) or adventitia (r = .53, P < .05) and with the plasma Ang II-to-Ang I ratio (r = .53, P < .05). Light microscopic autoradiographs of 125I-351A binding revealed a marked inhibition of ACE by perindopril in both layers of the vascular wall. CONCLUSIONS The present demonstrates that long-term administration of perindopril potently inhibits both endothelial and adventitial ACE to a comparable degree in the human internal mammary artery. These results indicate that perindopril effectively penetrates the vascular wall to inhibit ACE in the adventitia, thus providing evidence that perindopril may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall.
Can muscle stiffness alone stabilize upright standing?

A stiffness control model for the stabilization of sway has been proposed recently. This paper discusses two inadequacies of the model: modeling and empiric consistency. First, we show that the in-phase relation between the trajectories of the center of pressure and the center of mass is determined by physics, not by control patterns. Second, we show that physiological values of stiffness of the ankle muscles are insufficient to stabilize the body "inverted pendulum. " The evidence of active mechanisms of sway stabilization is reviewed, pointing out the potentially crucial role of foot skin and muscle receptors.
The Open University ’ s repository of research publications and other research outputs Collaboration in Pair Programming : driving and switching Conference Item

This paper reports on an empirical study about the mechanisms of the collaboration of drivers and navigators in Pair Programming (PP) sessions. Based on video recordings of professional software developers, we analysed the mechanisms of role switches and how developers split the task of driving. We found that developers do not evenly contribute to the task of driving and that they spend on average a third of the session without any computer interaction focusing mainly on communication. In addition, our results show that most pairs switch roles frequently and that the frequency and fluidity of switches indicate a high level of engagement on the part of both developers.
Activated escape over oscillating barriers: The case of many dimensions

We present a novel path‐integral method for the determination of time‐dependent and time‐averaged reaction rates in multidimensional, periodically driven escape problems at weak thermal noise. The so obtained general expressions are evaluated explicitly for the situation of a sinusoidally driven, damped particle with inertia moving in a metastable, piecewise parabolic potential. A comparison with data from Monte‐Carlo simulations yields a very good agreement with our analytic results over a wide parameter range.
Drug use, abuse, and dependence and the persistence of nicotine dependence.

INTRODUCTION Illicit drug use and nicotine dependence (ND) frequently co-occur. Yet, to date very few studies have examined the role of alcohol and illicit drug use in ND persistence. The objectives of this study were to investigate the relationships between specific classes of drug use, abuse, and dependence and the persistence of ND over time among adults in the United States. METHODS Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a national survey of 34,653U.S. adults interviewed between 2001-2002 and reinterviewed 3 years later. Logistic regression analyses were used to investigate the relationships between various classes of drug use, abuse, and dependence among adults with ND at Wave 1 and the odds for persistent ND at Wave 2. Analyses were adjusted for differences in demographic characteristics, mood/anxiety disorders, alcohol use disorders, and other substance use disorders. RESULTS Lifetime drug use was not associated with significantly increased likelihood for persistent ND. Sedative abuse was associated with increased odds for nicotine persistence, but no other types of drug abuse were predictive of ND persistence, after adjusting for demographics, mood/anxiety, and alcohol use disorders. All types of drug dependence were associated with persistence of ND; the strongest associations emerged between opioid and tranquilizer dependence and persistent ND, while the associations between cannabis and cocaine dependence were no longer significant after adjusting for mood/anxiety disorders. CONCLUSIONS Clinicians should take care to evaluate the presence and/or history of drug dependence among patients seeking treatment for smoking cessation. These data suggest that a history of substance dependence predicts increased vulnerability to persistent ND.
Operative versus non-operative treatment for closed, displaced, intra-articular fractures of the calcaneus: randomised controlled trial

Objective To investigate whether surgery by open reduction and internal fixation provides benefit compared with non-operative treatment for displaced, intra-articular calcaneal fractures. Design Pragmatic, multicentre, two arm, parallel group, assessor blinded randomised controlled trial (UK Heel Fracture Trial). Setting 22 tertiary referral hospitals, United Kingdom. Participants 151 patients with acute displaced intra-articular calcaneal fractures randomly allocated to operative (n=73) or non-operative (n=78) treatment. Main outcome measures The primary outcome measure was patient reported Kerr-Atkins score for pain and function (scale 0-100, 100 being the best possible score) at two years after injury. Secondary outcomes were complications; hindfoot pain and function (American Orthopaedic Foot and Ankle Society score); general health (SF-36); quality of life (EQ-5D); clinical examination; walking speed; and gait symmetry. Analysis was by intention to treat. Results 95% follow-up was achieved for the primary outcome (69 in operative group and 74 in non-operative group), and a complete set of secondary outcomes were available for 75% of participants. There was no significant difference in the primary outcome (mean Kerr-Atkins score 69.8 in operative group v 65.7 in non-operative group; adjusted 95% confidence interval of difference −7.1 to 7.0) or in any of the secondary outcomes between treatment groups. Complications and reoperations were more common in those who received operative care (estimated odds ratio 7.5, 95% confidence interval 2.0 to 41.8). Conclusions Operative treatment compared with non-operative care showed no symptomatic or functional advantage after two years in patients with typical displaced intra-articular fractures of the calcaneus, and the risk of complications was higher after surgery. Based on these findings, operative treatment by open reduction and internal fixation is not recommended for these fractures. Trial registration Current Controlled Trials ISRCTN37188541.
N‐terminal contributions of the γ‐subunit of fetal hemoglobin to its tetramer strength: Remote effects at subunit contacts

The greatly increased tetramer strength of liganded fetal hemoglobin compared with adult hemoglobin is shown by its 70‐fold smaller tetramer‐dimer dissociation constant. This property has been shown previously to be only partially caused by the 5‐amino‐acid differences at both types of interfaces in each hemoglobin. A major contributor to tetramer strengthening is the 18‐amino‐acid N‐terminal A helix of the γ‐subunit of fetal hemoglobin, which differs from the β‐subunit of adult hemoglobin at eight amino acid residues. This long‐distance communication between the A helix and the distant C helix and FG helical corner comprising the subunit contacts at the allosteric interface represents internal signaling. Physiologically, its greater tetramer strength endows fetal hemoglobin with the capacity to abstract oxygen from maternal adult hemoglobin. It also leads to resistance of fetal red cells to the malaria parasite because the HbF tetramer does not dissociate to dimers as readily as HbA; dimers are digested by malaria proteases but tetramers are not. In this communication, we report which sites on the A helix of the γ‐subunit are important for tetramer strengthening in HbF by substituting certain amino acids in the β‐subunit by the corresponding residues in the γ‐subunit. The recombinant hemoglobins containing up to five replacements together have been extensively characterized. Mass values were within 1 unit of theory. Gly 1 (γ) of HbF with its high pKa of 8.1 compared with a 7.1 value for Val 1 (β) of HbA creates a highly electropositive N terminus that may couple with the electronegative sequence just after it on the γ‐subunit. The Leu 3 to Phe replacement has no apparent role; however, position 5 is important because replacement of Pro 5 (β) by Glu 5 (γ) promotes tetramer strengthening. The Glu → Asp replacement at position 7 enhances this effect because of the lower pKa of Asp but the Val → Ile substitution at position 11 has no effect. Thus, the three positive/negative sites at positions 1, 5, and 7 account for practically all of the tetramer strength of HbF, as illustrated by an electrostatic surface potential analysis. The pathway by which information is transmitted to the distant allosteric subunit interfaces is currently under study. Oxygen‐binding properties of the hemoglobins with charged substitutions more closely resemble those of HbA rather than those of HbF. Thus, whereas the A helix has a major role in controlling the strength of interactions at the tetramer‐dimer allosteric interface, oxygen‐binding properties of HbA and HbF are influenced by sequences in the C helix and at the FG helical corner constituting the allosteric interface.
WCET Analysis of a Parallel 3D Multigrid Solver Executed on the MERASA Multi-Core

To meet performance requirements as well as constraints on cost and power consumption, future embedded systems will be designed with multi-core processors. However, the question of timing analysability is raised with these architectures. In the MERASA project, a WCET-aware multicore processor has been designed with the appropriate system software. They both guarantee that the WCET of tasks running on dierent cores can be safely analyzed since their possible interactions can be bounded. Nevertheless, computing the WCET of a parallel application is still not straightforward and a high-level preliminary analysis of the communication and synchronization patterns must be performed. In this paper, we report on our experience in evaluating the WCET of a parallel 3D multigrid solver code and we propose lines for further research on this topic.
Mushroom Cosmetics: The Present and Future

Mushrooms have been valued as a traditional source of natural bioactive compounds for centuries and have recently been exploited for potential components in the cosmetics industry. Numerous mushrooms and their ingredients have been known to be beneficial to the skin and hair. The representative ingredients are as follows: phenolics, polyphenolics, terpenoids, selenium, polysaccharides, vitamins, and volatile organic compounds. These compounds show excellent antioxidant, anti-aging, anti-wrinkle, skin whitening, and moisturizing effects, which make them ideal candidates for cosmetics products. This review provides some perspectives of mushrooms (and/or extracts) and their ingredients presently used, or patented to be used, in both cosmeceuticals for topical administration and nutricosmetics for oral administration. With the small percentage of mushrooms presently identified and utilized, more mushroom species will be discovered, verified, and cultivated in the future, boosting the development of relevant industry. Combining with progress in genomics, proteomics, metabolomics, and systems pharmacology, mushrooms can find their way into cosmetics with multiple approaches.
The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics

The retromer complex is required for the efficient endosome-to-Golgi retrieval of the CIMPR, sortilin, SORL1, wntless and other physiologically important membrane proteins. Retromer comprises two protein complexes that act together in endosome-to-Golgi retrieval; the cargo-selective complex is a trimer of VPS35, VPS29 and VPS26 that sorts cargo into tubules for retrieval to the Golgi. Tubules are produced by the oligomerization of sorting nexin dimers. Here, we report the identification of five endosomally-localised proteins that modulate tubule formation and are recruited to the membrane via interactions with the cargo-selective retromer complex. One of the retromer-interacting proteins, strumpellin, is mutated in hereditary spastic paraplegia, a progressive length-dependent axonopathy. Here, we show that strumpellin regulates endosomal tubules as part of a protein complex with three other proteins that include WASH1, an actin-nucleating promoting factor. Therefore, in addition to a direct role in endosome-to-Golgi retrieval, the cargo-selective retromer complex also acts as a platform for recruiting physiologically important proteins to endosomal membranes that regulate membrane tubule dynamics.
Detection of myocardial viability based on measurement of sodium content: A 23Na‐NMR study

MRI of total sodium (Na) content may allow assessment of myocardial viability, but information on Na content in normal myocardium, necrotic/scar tissue, and stunned or hibernating myocardium is lacking. Thus, the aims of the study were to: 1) quantify the temporal changes in myocardial Na content post‐myocardial infarction (MI) in a rat model (Protocol 1); 2) compare Na in normally perfused, hibernating, and stunned canine myocardium (Protocol 2); and 3) determine whether, in buffer‐perfused rat hearts, infarct scar can be differentiated from intact myocardium by 23Na‐MRI (Protocol 3). In Protocol 1, rats were subjected to LAD ligation. Infarct/scar tissue was excised at control and 1, 3, 7, 28, 56, and 128 days post‐MI (N = 6–8 each), Na content was determined by 23Na‐NMR spectroscopy (MRS) and ion chromatography. Na content was persistently increased at all time points post‐MI averaging 306*–160*% of control values (*P < 0.0083 vs. control). In Protocol 2, 23Na‐MRS of control (baseline), stunned and hibernating samples revealed no difference in Na. In Protocol 3, 23Na‐MRI revealed a mean increase in signal intensity, to 142 ± 6% of control values, in scar tissue. A threshold of 2 standard deviations of the image intensity allowed determination of infarct size, correlating with histologically determined infarct size (r = 0.91, P < 0.0001). Magn Reson Med 45:756–764, 2001. © 2001 Wiley‐Liss, Inc.
Revised intrauterine growth curves for an Australian hospital population

ABSTRACT. Intrauterine growth curves require periodic revision because of changes in population, socio‐economic factors and technology used in obstetric care. Anthropometric measurements were derived from consecutive livebirths in the Royal Women's Hospital in 1979 and all those born before 35 weeks in 1977 and 1978; at gestational ages less than 30 weeks, data previously published was also incorporated. Infants were included if an ultrasonic examination of the uterus had been performed in the first 20 weeks of pregnancy or gestation based on “certain” menstrual history was confirmed clinically. From data on 3120 infants, intrauterine growth curves from 24‐‐42 weeks' gestation were prepared; compared with births in the same hospital in 1966, there was generally an elevation of all centiles, particularly so for the 10th centile for weight after 37 weeks' gestation. Factors in the infant such as sex and ethnic origin and also maternal factors, especially pregnancy weight and height should be considered when using standard intrauterine growth charts.
Mesenchymal Stem Cells Derived from Human Gingiva Are Capable of Immunomodulatory Functions and Ameliorate Inflammation-Related Tissue Destruction in Experimental Colitis1

Aside from the well-established self-renewal and multipotent differentiation properties, mesenchymal stem cells exhibit both immunomodulatory and anti-inflammatory roles in several experimental autoimmune and inflammatory diseases. In this study, we isolated a new population of stem cells from human gingiva, a tissue source easily accessible from the oral cavity, namely, gingiva-derived mesenchymal stem cells (GMSCs), which exhibited clonogenicity, self-renewal, and multipotent differentiation capacities. Most importantly, GMSCs were capable of immunomodulatory functions, specifically suppressed peripheral blood lymphocyte proliferation, induced expression of a wide panel of immunosuppressive factors including IL-10, IDO, inducible NO synthase (iNOS), and cyclooxygenase 2 (COX-2) in response to the inflammatory cytokine, IFN-γ. Cell-based therapy using systemic infusion of GMSCs in experimental colitis significantly ameliorated both clinical and histopathological severity of the colonic inflammation, restored the injured gastrointestinal mucosal tissues, reversed diarrhea and weight loss, and suppressed the overall disease activity in mice. The therapeutic effect of GMSCs was mediated, in part, by the suppression of inflammatory infiltrates and inflammatory cytokines/mediators and the increased infiltration of regulatory T cells and the expression of anti-inflammatory cytokine IL-10 at the colonic sites. Taken together, GMSCs can function as an immunomodulatory and anti-inflammatory component of the immune system in vivo and is a promising cell source for cell-based treatment in experimental inflammatory diseases.
Effects of amisulpride on emotional memory using a dual-process model in healthy male volunteers

Memory dysfunction occurs in a number of neuropsychiatric disorders. Therapeutic psychopharmacological agents may exacerbate such memory impairment. Detailed characterisation of drug-induced memory impairment is therefore important. We recently showed that the D2/D3 antagonist amisulpride quantitatively impairs emotional memory in a randomised placebo-controlled study of 33 healthy volunteers. Current evidence suggests that two qualitatively different processes (recollection and familiarity) contribute to recognition memory and can be investigated using a Dual-Process Signal Detection model. Using such a model, we found that amisulpride levels at encoding were significantly inversely correlated with recollection estimates for emotional but not neutral stimuli or familiarity estimates in healthy male volunteers. This suggests that dopamine antagonism at encoding preferentially impairs the recollection component of emotional memory, relative to the familiarity component. This was supported by receiver operating characteristic analysis. We also found a significantly increased false recognition rate, associated with significantly shorter reaction times for emotional but not neutral stimuli in the amisulpride group. These findings have important implications for our understanding of recognition memory processes, as well as the interpretation of neuropsychological findings in medicated patients.
Indirect Reciprocity and Strategic Reputation Building in an Experimental Helping Game

We study indirect reciprocity and strategic reputation building in an experimental helping game. At any time only half of the subjects can build a reputation. This allows us to study both pure indirect reciprocity that is not contaminated by strategic reputation building and the impact of incentives for strategic reputation building on the helping rate. We find that while pure indirect reciprocity appears to be important, the helping choice seems to be influenced at least as much by strategic considerations. Strategic do better than non-strategic players and non-reciprocal do better than reciprocal players, casting doubt on previously proposed evolutionary explanations for indirect reciprocity.
Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide

CD138 expression is a hallmark of plasma cells and multiple myeloma cells. However, decreased expression of CD138 is frequently observed in plasma cells of myeloma patients, although the clinical significance of this is unclear. To evaluate the significance of low expression of CD138 in MM, we examined the phenotypes of MM cells expressing low levels of CD138. Flow cytometric analysis of primary MM cells revealed a significant decrease in CD138 expression in patients with relapsed/progressive disease compared with untreated MM patients. Patients with low levels of CD138 had a worse overall survival compared with patients with high levels of CD138, in newly diagnosed patients and patients receiving high-dose chemotherapy followed by autologous stem-cell transplantation. Two MM cell lines, KYMM-1 (CD138− low) and KYMM-2 (CD138− high), were established from a single MM patient with decreased CD138 expression. High expression of BCL6 and PAX5, and downregulation of IRF4, PRDM1 and XBP1 was observed in KYMM-1 compared with KYMM-2 cells, indicative of the immature phenotype of KYMM-1. KYMM-1 was less sensitive to lenalidomide than KYMM-2, while no difference in sensitivity to bortezomib was observed. KYMM-2 cells were further divided in CD138+ and CD138− fractions using anti-CD138-coated magnetic beads. CD138− cells sorted from the KYMM-2 cell line also showed high BCL6, low IRF4 expression and decreased sensitivity to lenalidomide compared with CD138+ cells. Our observations suggest that low CD138 expression relates to i) poor prognosis, ii) immature phenotype and iii) low sensitivity to lenalidomide. The observed distinct characteristics of CD138 low MM cells, suggest this should be recognized as a new clinical entity. Establishment of a treatment strategy for MM cells expressing low levels of CD138 is needed to improve their poor outcome.