Miracle-dz/UniFAR-FTUs huggingface dataset:
Fluid-induced propulsion of rigid particles in wormlike micellar solutions

In the absence of inertia, a reciprocal swimmer achieves no net motion in a viscous Newtonian fluid. Here, using tracking methods and birefringence imaging, we investigate the ability of a reciprocally actuated particle to translate through a complex fluid that possesses a network. A geometrically polar particle, a rod with a bead on one end, is reciprocally rotated using magnetic fields. The particle is immersed in a wormlike micellar (WLM) solution that is known to be susceptible to the formation of shear bands and other localized structures due to shear-induced remodeling of its microstructure. Results show that the nonlinearities present in this WLM solution break time-reversal symmetry under certain conditions, and enable propulsion of an artificial “swimmer. ” We find three regimes dependent on the Deborah number (De): net motion towards the bead-end of the particle at low De, net motion towards the rod-end of the particle at intermediate De, and no appreciable propulsion at high De. At low De, where the particle time scale is longer than the fluid relaxation time, we believe that propulsion is caused by an imbalance in the fluid first normal stress differences between the two ends of the particle (bead and rod). At De ∼ 1, however, we observe the emergence of a region of network anisotropy near the rod using birefringence imaging. This anisotropy suggests alignment of the micellar network, which is “locked in” due to the shorter time scale of the particle relative to the fluid.
The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms.

Metformin is regarded as an antihyperglycaemic agent because it lowers blood glucose concentrations in type 2 (non-insulin-dependent) diabetes without causing overt hypoglycaemia. Its clinical efficacy requires the presence of insulin and involves several therapeutic effects. Of these effects, some are mediated via increased insulin action, and some are not directly insulin dependent. Metformin acts on the liver to suppress gluconeogenesis mainly by potentiating the effect of insulin, reducing hepatic extraction of certain substrates (e.g. lactate) and opposing the effects of glucagon. In addition, metformin can reduce the overall rate of glycogenolysis and decrease the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake into skeletal muscle is enhanced by metformin. This has been attributed in part to increased movement of insulin-sensitive glucose transporters into the cell membrane. Metformin also appears to increase the functional properties of insulin- and glucose-sensitive transporters. The increased cellular uptake of glucose is associated with increased glycogen synthase activity and glycogen storage. Other effects involved in the blood glucose-lowering effect of metformin include an insulin-independent suppression of fatty acid oxidation and a reduction in hypertriglyceridaemia. These effects reduce the energy supply for gluconeogenesis and serve to balance the glucose-fatty acid (Randle) cycle. Increased glucose turnover, particularly in the splanchnic bed, may also contribute to the blood glucose-lowering capability of metformin. Metformin improves insulin sensitivity by increasing insulin-mediated insulin receptor tyrosine kinase activity, which activates post-receptor insulin signalling pathways. Some other effects of metformin may result from changes in membrane fluidity in hyperglycaemic states. Metformin therefore improves hepatic and peripheral sensitivity to insulin, with both direct and indirect effects on liver and muscle. It also exerts effects that are independent of insulin but cannot substitute for this hormone. These effects collectively reduce insulin resistance and glucotoxicity in type 2 diabetes.
Thrombolytic therapy for acute ischaemic stroke in octogenarians: selection by magnetic resonance imaging improves safety but does not improve outcome

Background: Owing to the fear of an increased bleeding risk, thrombolytic therapy is withheld from many patients with acute stroke >80 years of age. Objective: To analyse the risk for symptomatic intracranial haemorrhage (sICH), morbidity and mortality after thrombolytic therapy in octogenarians focusing, in particular, on whether patients selected using magnetic resonance imaging (MRI) had a better risk:benefit ratio. Methods: The prospectively collected single-centre data of all patients treated with systemic thrombolytic therapy for acute ischaemic stroke since 1998 (n = 468) were reviewed, and patients ⩾80 years (n = 90) were compared with those aged <80 years (n = 378). In addition, the group of octogenarians was analysed with respect to initial imaging modality. Results: The overall rate of sICH in the octogenarians was 6.9%, compared with 5.3% in younger patients (p = 0.61). In older patients selected by computed tomography, the rate of sICH was 9.4%; no patient selected by MRI had sICH (p = 0.10). Mortality in the octogenarians selected by computed tomography was 29.7% after 3 months as compared with 26.9% in the patients selected by MRI (p = 1.0). 20.3% of the octogenarians selected by computed tomography and 15.4% of those selected by MRI had a favourable outcome (modified Rankin scale ⩽1) after 3 months (p = 0.77). Conclusion: Compared with younger patients, octogenarians do not have an increased risk of sICH. The use of MRI to select octogenarians for thrombolytic therapy seemed to decrease the risk of sICH, but did not influence the overall outcome after 3 months.
Spatio-temporal modelling of extreme storms

A flexible spatio-temporal model is implemented to analyse extreme extra-tropical cyclones objectively identified over the Atlantic and Europe in 6-hourly re-analyses from 1979-2009. Spatial variation in the extremal properties of the cyclones is captured using a 150 cell spatial regularisation, latitude as a covariate, and spatial random effects. The North Atlantic Oscillation (NAO) is also used as a covariate and is found to have a significant effect on intensifying extremal storm behaviour, especially over Northern Europe and the Iberian peninsula. Estimates of lower bounds on minimum sea-level pressure are typically 10-50 hPa below the minimum values observed for historical storms with largest differences occurring when the NAO index is positive.
Use of emergency departments by primary care patients

Introduction In many Western countries, accident and emergency (A&E) departments are frequently attended. Apparently this phenomenon occurs in countries with less (i.e. Spain’) and more (i.e. the Netherlands*) structured healthcare systems. As a result, overcrowding of A&E departments hinders urgent healthcare delivery. In some countries (as in Belgium) general practitioners (GPs) provide continuous out-of-hours services while A&E departments have free access. In Belgium patients d o not pay direct fees a t the A&E department, whereas a t a GP surgery they do. We studied patients’ reasons for visiting an A&E department and the appropriateness of these visits. A patient’s visit was judged ‘appropriate’ if the hospital consultant was of the opinion that a GP in primary care could not have treated the patient properly.
Rapid increase in clusters of synaptophysin at onset of homosynaptic potentiation in Aplysia

Imaging studies have shown that even the earliest phases of long-term plasticity are accompanied by the rapid recruitment of synaptic components, which generally requires actin polymerization and may be one of the first steps in a program that can lead to the formation of new stable synapses during late-phase plasticity. However, most of those results come from studies of long-term potentiation in rodent hippocampus and might not generalize to other forms of synaptic plasticity or plasticity in other brain areas and species. For example, recruitment of presynaptic proteins during long-term facilitation by 5HT in Aplysia is delayed for several hours, suggesting that whereas activity-dependent forms of plasticity, such as long-term potentiation, involve rapid recruitment of presynaptic proteins, neuromodulatory forms of plasticity, such as facilitation by 5HT, involve more delayed recruitment. To begin to explore this hypothesis, we examined an activity-dependent form of plasticity, homosynaptic potentiation produced by tetanic stimulation of the presynaptic neuron in Aplysia. We found that homosynaptic potentiation involves presynaptic but not postsynaptic actin and a rapid (under 10 min) increase in the number of clusters of the presynaptic vesicle-associated protein synaptophysin. These results indicate that rapid recruitment of synaptic components is not limited to hippocampal potentiation and support the hypothesis that activity-dependent types of plasticity involve rapid recruitment of presynaptic proteins, whereas neuromodulatory types of plasticity involve more delayed recruitment.
Osteoblastic differentiation and mRNA analysis of STRO‐1‐postitive human bone marrow stromal cells using primary in vitroculture and poly (A) PCR

Investigation of osteoblast dysfunction in osteoporosis has been hampered by a poor understanding of normal early osteoblast differentiation, due to a relative lack of markers for the earliest cells in the lineage. Attempts to identify such markers have used cultures of animal or immortalized human cells, of uncertain relevance to human biology, or heterogeneous cultures in which genetic variability precludes the isolation of stage‐specific genotypic markers. Primary in vitro generation of clonal populations of human bone marrow stromal cells was used in order to overcome these problems. Fibroblast‐like stromal cells were isolated from human sternal bone marrow. They showed differentiation to an osteoblastic phenotype when stimulated with dexamethasone (10−7 m) and fluorescence activated cell analysis demonstrated immunopositivity for STRO‐1 (an antibody that recognizes osteoprogenitor stem cells of the colony‐forming unit‐fibroblastic) in from 8 to 40 per cent of the cells, dependent on time post‐harvest. Cells positive for STRO‐1 were immunoselected using magnetic activated cell sorting and seeded at low density (10 cells/cm2 ) to produce clones. Each clone was subpassaged, osteoblastic differentiation stimulated with dexamethasone, and mRNA‐extracted at time points post‐stimulation (0h and 1–14 days). A novel poly (A) reverse transcriptase‐polymerase chain reaction (RT‐PCR) was used to amplify cDNA representative of all transcripts expressed at each time point. Differential gene expression within the amplified cDNA was assessed using 3′ end cDNA probes to osteocalcin, osteopontin, and collagen type I (positive), demonstrating the acquisition of an osteoblastic phenotype. Time‐specific gene products for early osteoblast differentiation have been generated from primary human cultures, utilizing very low density seeding and poly (A) RT‐PCR. These products overcome the problems associated with animal, immortalized or heterogeneous culture and can be used to study normal and altered early osteoblast differentiation, indicating the possibility of using the same system to study other disease states. Copyright © 1999 John Wiley & Sons, Ltd.
Incidence and Distribution of Vaginal Yeasts in Malaysian Women: Häufigkeit und Verteilung vaginaler Hefen bei malaysischen Frauen

Summary: A total of 2 153 high vaginal swabs were processed for the presence of yeasts. The specimens were obtained from pregnant and non‐pregnent Malaysian women with and without vaginitis. The yeast species most commonly isolated were Candida albicans, C. glabrata, C. famata and C. parapsilosis. C. albicanswas isolated from 27 % of pregnant women with vaginitis, 14% of pregnant women with no overt vaginitis, 15% of non‐pregnant women with vaginitis, and 3% of non‐pregnant women with no vaginitis. The significant difference of the isolation rates from women with and without vaginitis indicates that C. albicans is likely to be a vaginal pathogen.
Design of Distributed LTI Observers for State Omniscience

Consider that an autonomous linear time-invariant (LTI) plant is given and that each member of a network of LTI observers accesses a portion of the output of the plant. The dissemination of information within the network is dictated by a pre-specified directed graph in which each vertex represents an observer. This paper proposes a distributed estimation scheme that is a natural generalization of consensus in which each observer computes its own state estimate of the plant using only the portion of the output vector accessible to it and the state estimates of other observers that, according to the graph, are available to it. Unlike straightforward high-order solutions in which each observer broadcasts its measurements throughout the network, the average dimension of the state of each observer in the proposed scheme does not exceed the order of the plant plus one. We determine necessary and sufficient conditions for the existence of a parameter choice for which the proposed scheme attains asymptotic omniscience of the state of the plant at all observers. The conditions reduce to certain detectability requirements that imply that if omniscience is not possible under the proposed scheme then it is not viable under any other scheme—including higher-order LTI, nonlinear, and time-varying ones—subject to the same graph.
Expression and activation of alpha v beta 3 integrins by SDF-1/CXC12 increases the aggressiveness of prostate cancer cells.

BACKGROUND Stromal cell-derived factor-1 (SDF-1 or CXCL12) and CXCR4 are key elements in the metastasis of prostate cancer cells to bone--but the mechanisms as to how it localizes to the marrow remains unclear. METHODS Prostate cancer cell lines were stimulated with SDF-1 and evaluated for alterations in the expression of adhesion molecules using microarrays, FACs, and Western blotting to identify alpha(v)beta(3) receptors. Cell-cell adhesion and invasion assays were used to verify that activation of the receptor is responsive to SDF-1. RESULTS We demonstrate that SDF-1 transiently regulates the number and affinity of alpha(v)beta(3) receptors by prostate cancer cells to enhance their metastatic behavior by increasing adhesiveness and invasiveness. SDF-1 transiently increased the expression of beta(3) receptor subunit and increased its phosphorylation in metastatic but not nonmetastatic cells. CONCLUSIONS The transition from a locally invasive phenotype to a metastatic phenotype may be primed by the elevated expression of alpha(v)beta(3) receptors. Activation and increased expression of alpha(v)beta(3) within SDF-1-rich organs may participate in metastatic localization.
Consent for genetics studies among clinical trial participants: findings from Action for Health in Diabetes (Look AHEAD)

Background Increasingly, genetic specimens are collected to expand the value of clinical trials through study of genetic effects on disease incidence, progression or response to interventions. Purpose and methods We describe the experience obtaining IRB-approved DNA consent forms across the 19 institutions in the Action for Health in Diabetes (Look AHEAD), a clinical trial examining the effect of a lifestyle intervention for weight loss on the risk of serious cardiovascular events among individuals with type 2 diabetes. We document the rates participants provided consent for DNA research, identify participant characteristics associated with consent, and discuss implications for genetics research. Results IRB approval to participate was obtained from 17 of 19 institutions. The overall rate of consent was 89.6% among the 15 institutions that had completed consenting at the time of our analysis, which was higher than reported for other types of cohort studies. Consent rates were associated with factors expected to be associated with weight loss and cardiovascular disease and to affect the distribution of candidate genes. Non-consent occurred more frequently among participants grouped as African-American, Hispanic, female, more highly educated or not dyslipidemic. Limitations The generalizabilty of results is limited by the inclusion/exclusion criteria of the trial. Conclusions Barriers to obtaining consent to participate in genetic studies may differ from other recruitment settings. Because of the potentially complex associations between personal characteristics related to adherence, outcomes and gene distributions, differential rates of consent may introduce biases in estimates of genetic relationships.
Calidad sanitaria en queso artesanal tipo telita. Upata, estado Bolívar, Venezuela

En este trabajo se investigaron microorganismos indicadores de calidad sanitaria en queso artesanal tipo “telita” de Upata,municipio Piar, estado Bolivar. Se analizaron 60 muestras y se investigaron estafilococos coagulasa positivos (Staphylococcus aureus)segun Norma Venezolana COVENIN 1292-89 como indicador de manipulacion; bacterias coliformes segun Norma VenezolanaCOVENIN 1104-96 y presencia de Escherichia coli como indicador de contaminacion fecal. Todos los crecimientos bacterianos correspondierona estafilococos coagulasa negativos con recuentos de hasta 104 diluciones decimales. Coliformes totales mostraron recuentos dehasta ≤105 NMP/g y coliformes fecales en concentracion ≤104 NMP/g. Escherichia coli estuvo presente en 43,3% de los quesos. Se concluyoque el queso artesanal tipo “telita” que se expende en los alrededores de Upata, estado Bolivar, evidencia fallas en la manipulacione higiene posterior a su elaboracion; y por no cumplir con los criterios que establece el Reglamento Centroamericano de Criterios Microbiologicosde los Alimentos Procesados, se considera un producto que podria representar un alto riesgo microbiologico para el consumidor.
Clinical teachers as humanistic caregivers and educators: perceptions of senior clerks and second-year residents.

BACKGROUND The acquisition and nurturing of humanistic skills and attitudes constitute an important aim of medical education. In order to assess how conducive the physician-learning environment is to the acquisition of these skills, the authors determined the extent to which clinical teachers are perceived by their trainees as humanistic with patients and students, and they explored whether undergraduate and graduate students share the same perceptions. METHODS A mail survey was conducted in 1994/95 of all senior clerks and second-year residents at Laval University, University of Montreal and University of Sherbrooke medical schools. Of 774 trainees, 259 senior clerks and 238 second-year residents returned the questionnaire, for an overall response rate of 64%. Students' perceptions of their teachers were measured on a 6-point Likert scale applied to statements about teachers' attitudes toward the patient (5 items) and toward the student (5 items). RESULTS On average, only 46% of the senior clerks agreed that their teachers displayed the humanistic characteristics of interest. They were especially critical of their teachers' apparent lack of sensitivity, with as many as 3 out of 4 declaring that their teachers seemed to be unconcerned about how patients adapt psychologically to their illnesses (75% of clerks) and that their teachers did not try to understand students' difficulties (78%) or to support students who have difficulties (77%). Compared with the clerks, the second-year residents were significantly less critical, those with negative perceptions varying from 27% to 58%, 40% on average. Except for this difference, their pattern of responses from one item to another was similar. INTERPRETATION This study suggests the existence of a substantial gap between what medical trainees are expected to learn and what they actually experience over the course of their training. Because such a gap could represent a significant barrier to the acquisition of important skills, more and urgent research is needed to understand better the factors influencing students' perceptions.
Modelling and exploring human sleep with event history analysis

In this paper we propose the use of statistical models of event history analysis for investigating human sleep. These models provide appropriate tools for statistical evaluation when sleep data are recorded continuously over time or on a fine time grid, and are classified into sleep stages such as REM and nonREM as defined by Rechtschaffen and Kales (1968). In contrast to conventional statistical procedures, event history analysis makes full use of the information contained in sleep data , and can therefore provide new insights into non‐stationary properties of sleep. Probabilities of or intensities for transitions between sleep stages are the basic quantities for characterising sleep processes. The statistical methods of event history analysis aim at modelling and estimating these intensities as functions of time, taking into account individual sleep history and assessing the influence of factors of interest, such as hormonal secretion. In this study we suggest the use of non‐parametric approaches to reveal unknown functional forms of transition intensities and to explore time‐varying and non‐stationary effects. We then apply these techniques in a study of 30 healthy male volunteers to assess the mean population intensity and the effects of plasma cortisol concentration on the transition between selected sleep stages as well as the influence of elapsed time in a current REM period on the intensity for a transition to nonREM. The most interesting findings are that (a) the intensity of the nonREM‐to‐REM transitions after sleep onset in young men shows a periodicity which is similar to that of nonREM/REM cycles; (b) 30–45 min after sleep onset, young men reveal a great propensity to pass from light sleep (stages 1 or 2) into slow‐wave sleep (SWS) (stages 3 or 4); (c) high cortisol levels imposed additional impulses on the transition intensity of (i) wake to sleep around 2 h after sleep onset, (ii) nonREM to REM around 6 h later, (iii) stage 1 or stage 2 sleep to SWS around 2, 4 and 6 h later and (iv) SWS to stage 1 or stage 2 sleep about 2 h later. Moreover, high cortisol concentrations at the beginning of REM periods favoured the change to nonREM sleep, whereas later their influence on a nonREM change became weak and weaker. As sleep data are also available as event‐oriented data in many studies in sleep research, event history analysis applied additionally to conventional statistical procedures, such as regression analysis or analyis of variance, could help to acquire more information and knowledge about the mechanisms behind the sleep process.
Cell Surface Heparan Sulfate Is a Receptor for Human Herpesvirus 8 and Interacts with Envelope Glycoprotein K8.1

ABSTRACT An immunodominant envelope glycoprotein is encoded by the human herpesvirus 8 (HHV-8) (also termed Kaposi's sarcoma-associated herpesvirus) K8.1 gene. The functional role of glycoprotein K8.1 is unknown, and recognizable sequence homology to K8.1 is not detectable in the genomes of most other closely related gammaherpesviruses, such as herpesvirus saimiri or Epstein-Barr virus. In search for a possible function for K8.1, we expressed the ectodomain of K8.1 fused to the Fc part of human immunoglobulin G1 (K8.1ΔTMFc). K8.1ΔTMFc specifically bound to the surface of cells expressing glycosaminoglycans but not to mutant cell lines negative for the expression of heparan sulfate proteoglycans. Binding of K8.1ΔTMFc to mammalian cells could be blocked by heparin. Interestingly, the infection of primary human endothelial cells by HHV-8 could also be blocked by similar concentrations of heparin. The specificity and affinity of these interactions were then determined by surface plasmon resonance measurements using immobilized heparin and soluble K8.1. This revealed that K8.1 binds to heparin with an affinity comparable to that of glycoproteins B and C of herpes simplex virus, which are known to be involved in target cell recognition by binding to cell surface proteoglycans, especially heparan sulfate. We conclude that cell surface glycosaminoglycans play a crucial role in HHV-8 target cell recognition and that HHV-8 envelope protein K8.1 is at least one of the proteins involved.