Miracle-dz/UniFAR-FTUs huggingface dataset:
PPARβ/δ directs the therapeutic potential of mesenchymal stem cells in arthritis

Objectives To define how peroxisome proliferator-activated receptor (PPAR) β/δ expression level in mesenchymal stem cells (MSCs) could predict and direct both their immunosuppressive and therapeutic properties. PPARβ/δ interacts with factors such as nuclear factor-kappa B (NF-κB) and regulates the expression of molecules including vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1. Since these molecules are critical for MSC function, we investigated the role of PPARβ/δ on MSC immunosuppressive properties. Methods We either treated human MSCs (hMSCs) with the irreversible PPARβ/δ antagonist (GSK3787) or derived MSCs from mice deficient for PPARβ/δ (PPARβ/δ−/− MSCs). We used the collagen-induced arthritis (CIA) as model of immune-mediated disorder and the MSC-immune cell coculture assays. Results Modulation of PPARβ/δ expression in hMSCs either using GSK3787 or hMSCs from different origin reveals that MSC immunosuppressive potential is inversely correlated with Ppard expression. This was consistent with the higher capacity of PPARβ/δ−/− MSCs to inhibit both the proliferation of T lymphocytes, in vitro, and arthritic development and progression in CIA compared with PPARβ/δ+/+ MSCs. When primed with proinflammatory cytokines to exhibit an immunoregulatory phenotype, PPARβ/δ−/− MSCs expressed a higher level of mediators of MSC immunosuppression including VCAM-1, ICAM-1 and nitric oxide (NO) than PPARβ/δ+/+ MSCs. The enhanced NO2 production by PPARβ/δ−/− MSCs was due to the increased retention of NF-κB p65 subunit on the κB elements of the inducible nitric oxide synthase promoter resulting from PPARβ/δ silencing. Conclusions Our study is the first to show that the inhibition or knockdown of PPARβ/δ in MSCs primes their immunoregulatory functions. Thus, the regulation of PPARβ/δ expression provides a new strategy to generate therapeutic MSCs with a stable regulatory phenotype.
Visualization of the Particle Dendrite Deposition Phenomenon by Using Computer Technology

The phenomenon of dust particles surface deposition in the fibrous medium showed the dendrites structures, which had been confirmed and could be visualized by using computer technology for better understanding particle deposition behavior on filtration process of fibrous media. The pseudo-random movement model was used and the impact of particle inertia movement and diffusion movement on the dust cake growth process in the fibrous filtration media surface were studied by simulation. The simulation method and programs were introduced in detail in the paper, and the result simulation of particle deposition was in good agreement with experimental test result. The results showed that more irregular the dust cake morphology structure was, the greater the dust particles dispersion was and the greater dust cake porosity was.
A Seven-degrees-of-freedom Robot-arm Driven by Pneumatic Artificial Muscles for Humanoid Robots

Braided pneumatic artificial muscles, and in particular the better known type with a double helical braid usually called the McKibben muscle, seem to be at present the best means for motorizing robot-arms with artificial muscles. Their ability to develop high maximum force associated with lightness and a compact cylindrical shape, as well as their analogical behavior with natural skeletal muscle were very well emphasized in the 1980s by the development of the Bridgestone “soft robot” actuated by “rubbertuators”. Recent publications have presented ways for modeling McKibben artificial muscle as well as controlling its highly non-linear dynamic behavior. However, fewer studies have concentrated on analyzing the integration of artificial muscles with robot-arm architectures since the first Bridgestone prototypes were designed. In this paper we present the design of a 7R anthropomorphic robot-arm entirely actuated by antagonistic McKibben artificial muscle pairs. The validation of the robot-arm architecture was performed in a teleoperation mode.
High-contrast algorithm behavior: observation, conjecture, and experimental design

After extensive experiments with two algorithms, CPLEX and our implementation of all-integer dual simplex, we observed extreme differences between the two on a set of design automation benchmarks. In many cases one of the two would find an optimal solution within seconds while the other timed out at one hour. We conjecture that this contrast is accounted for by the extent to which the constraint matrix can be made block diagonal via row/column permutations. The actual structure of the matrix without the permutations is not important. Our conjecture is made more precise in two steps: (a) crossing minimization is used on a derived graph to achieve desirable permutations of rows and columns; and (b) the degree of randomness (lack of structure) is measured using diffusion, a measure that approximates what a human perceives as lack of structure. Additional experiments on synthetic instances related to the benchmarks add validity to our conjecture. We observe unexpectedly sharp thresholds where, with only slight variation of our measure, the dominance of the algorithms reverses dramatically. The nature of and explanation for this threshold behavior is left for future research as are many other questions. As far as we are aware the approach taken here is unique and, we hope, will inspire other research of its kind.
Phytoplankton community of the drinking water supply reservoir Borovitsa (South Bulgaria) with an emphasis on cyanotoxins and water quality

The phytoplankton diversity, algal biomass, and selected physicochemical parameters were investigated in the drinking water reservoir (Borovitsa) located in the Kardzhali region, Bulgaria. Particular attention was given to Cyanoprokaryota and presence of cyanotoxins in the water samples. Twenty-nine species belonging to six divisions (Cyanoprokaryota, Chlorophyta, Zygnemophyta, Dinophyta, Euglenophyta and Bacillariophyta) were identified. The microscopic examination of the phytoplankton samples showed the dominance of Ankyra judayi, Oocystis lacustris (Chlorophyta) and Aphanizomenon flos-aquae (Cyanoprokaryota) in July 2006, and Microcystis pulverea, Synechococcus elongatus (Cyanoprokaryota), Radiococcus planktonicus (Chlorophyta) and Melosira varians (Bacillariophyta) in September 2006. A blooming event due to Aphanizomenon flos-aquae was observed in July 2006. The reservoir exhibits a tendency to shift from an oligotrophic environment to a state of mesotrophy. Presence of cyanotoxins such as anatoxin-a, microcystins and saxitoxins were analyzed by HPLC and ELISA methods. Our results demonstrated the presence of anatoxin-a and microcystins (0.09 µg/L) in the raw water samples from July 2006, and saxitoxins (2.5 µg/L) and microcystins (0.18 µg/L) in the raw water samples from September 2006. The study underlines that permanent monitoring programs of Cyanoprokaryota in the reservoirs used as sources of drinking water and toxicity assessments should be implemented. Indirect exposure and transfer of cyanotoxins through food chains must also be considered.
Culture Period-Dependent Change of Function and Expression of ATP-Binding Cassette Transporters in Caco-2 Cells

The objective of this study was to determine an appropriate culture period to assess whether a compound of interest is transported by efflux transporters such as human multidrug resistance 1 (hMDR1), human multidrug resistance-associated protein 2 (hMRP2), and human breast cancer resistance protein (hBCRP) in Caco-2 cells. Caco-2 cells were cultured on a Transwell for 1 to 6 weeks. The expression of these transporters in the mRNA and protein levels was examined using a real-time polymerase chain reaction and Western blotting, respectively. Transcellular transport activities using digoxin, ochratoxin A, olmesartan, and estrone-3-sulfate were also examined. Except for digoxin, the permeability coefficient (Papp) ratio of the three compounds at 2 weeks was the highest in the periods tested. The Papp ratio of digoxin at 2 weeks was higher than that at 3 weeks. The temporal expression profile of each transporter in the mRNA level was similar to that in the protein level, and the functions of hMRP2 and hBCRP were roughly correlated with the expression in the mRNA and protein levels, but that of hMDR1 was not. These data suggest that among all the culture periods evaluated a 2-week culture is the best culture period for transport studies to identify whether a compound is a substrate for hMDR1, hMRP2, and hBCRP.
Optimization of operating conditions in photon-counting multi-slit mammography based on Si-strip detectors

Measurements and simulations of the signal-difference-to-noise ratio (SDNR) and average glandular dose (AGD) have been performed on a photon counting full-field digital mammography system to determine the optimal operating conditions. Several beam qualities were experimentally evaluated by using different combinations of tube voltage, added filters and thickness of BR12 with a tungsten target x-ray tube. The SDNR and AGD were also calculated theoretically for an extended number of operating conditions and a more accurate breast model. As figure of merit for each operating condition, a spectral quantum efficiency (SQE) was calculated as the polychromatic SDNR squared over the optimal monochromatic SDNR squared at the same AGD. The theoretical model agreed within ±4% relative the measured SDNR throughout the evaluated breast thickness (30-70 mm) and tube voltage range (26-38 kV). The optimization was performed with a constant SDNR-rate as compared to using a fixed filter thickness. The optimal combinations of tube voltage-filter material were: 32 kV-Ag, 34 kV-Cd, 36 kV-Sn for a breast thickness of 30, 50 and 70 mm respectively. These K-edge filter materials increased the SQE by less than 4% compared to the optimal Al filtration.
On-line identification of MIMO evolving Takagi- Sugeno fuzzy models

Evolving Takagi-Sugeno (eTS) fuzzy models and the method for their on-line identification has been recently introduced as an effective tool for design of flexible system models with minimum a priori information. Their structure develops on-line during the process of model identification itself. In this paper, this approach has been extended for the case of multi-input multi-output (MIMO) system model. Both parts of the identification algorithm, namely the unsupervised fuzzy rule-base antecedents learning by a recursive, noniterative clustering, and the supervised linear sub-model parameters learning by Kalman-filtering-based procedure, are extended for the MIMO case. The radius of influence of each fuzzy rule is considered a vector instead of a scalar as in the original eTS approach, allowing different areas of the data space to be covered by each input variable. As in the eTS, in MIMO eTS, the rule-base and parameters of the fuzzy model continually evolve by adding new rules with more summarization power and by modifying existing rules and parameters. Simulation results using a well-known benchmark are considered in this paper. Further investigation concern the application of MIMO eTS to predictive modeling of the speech spectrum magnitude, classification of multi-channel source modulation etc.
Rating the Risk Factors for Breast Cancer

ObjectiveTo update and summarize evidence of risk factors for breast cancer. Summary Background DataWomen who are at high risk for breast cancer have a variety of options available to them, including watchful waiting, prophylactic surgery, and chemoprevention. It is increasingly important to accurately assess a patient’s risk profile to ensure that the cost/benefit ratio of the selected treatment is favorable. MethodsEstimates of relative risk for documented risk factors were obtained from seminal papers identified in previous reviews. These estimates were updated where appropriate with data from more recent reports using large sample sizes or presenting meta-analyses of previous studies. These reports were identified from a review of the Medline database from 1992 to 2002. ResultsRisk factors that have received a great deal of publicity (hormone use, alcohol consumption, obesity, nulliparity) present a relatively modest relative risk for breast cancer (<2). Factors associated with a prior history of neoplastic disease or atypical hyperplasia and factors associated with a genetic predisposition significantly affect the risk of breast cancer, with relative risks ranging from 3 (for some cases of positive family history) to 200 (for premenopausal women positive for a BRCA mutation). ConclusionsMore precise tools, based on techniques of molecular biology such as microarray analysis, will be needed to assess individual risk for breast cancer.
Oncostatin M induces procoagulant activity in human vascular smooth muscle cells by modulating the balance between tissue factor and tissue factor pathway inhibitor

Oncostatin M (OSM) is a cytokine of the interleukin-6 (IL-6) family secreted by activated monocytes, and is expressed in atherosclerotic plaque. Smooth muscle cells (SMC), by expressing tissue factor (TF) and tissue factor pathway inhibitor (TFPI) can contribute to the thrombogenicity of atherosclerotic plaque. Consequently, the aim of this study was to evaluate the effects of OSM on the procoagulant activity of SMC. We observed that OSM induced in a concentration-dependent manner a potent procoagulant activity (PCA) that was related in part to an increased synthesis of TF, both at the cell membrane and in SMC lysates. The increased expression of TF on SMC membrane induced by OSM was sustained and was still observed 24 h after stimulation by OSM. IL-6 and leukaemia inhibitory factor (LIF), two OSM-related cytokines, did not significantly modify TF expression at the surface of SMC. In addition to its effects on TF, OSM decreased the secretion of TFPI in the supernatants of SMC, as well as in the lysates, but was devoid of effect on TFPI bound at the membrane of SMC. IL-6 and LIF reduced also TFPI secretion, which could explain why the PCA of SMC lysates treated by IL-6 or LIF was increased, despite an absence of effect on TF expression. In conclusion, these data support the hypothesis that by increasing the PCA of SMC, OSM might be involved in the thrombotic complications associated with plaque rupture.
Clinimetric properties of bronchoalveolar lavage inflammatory markers in cystic fibrosis

The Standardisation Committee of the European Cystic Fibrosis Society Clinical Trial Network has undertaken the evaluation of clinical end-points for therapeutic interventions regarding their use in multicentre clinical trials in cystic fibrosis (CF). This review of biomarkers in bronchoalveolar lavage (BAL) is part of the group’s work. The aims of this project were: 1) to review the literature on reliability, validity and responsiveness of BAL in patients with CF; 2) to gain consensus of the group on the feasibility of BAL; and 3) to gain consensus on answers to key questions regarding the promotion of BAL to surrogate end-point status. Assessment of BAL inflammatory markers in the literature indicates that their reliability, validity and responsiveness are adequate for clinical trials. After discussion of the practical characteristics it was concluded that BAL has an attractive validity profile, albeit with limited feasibility. It is particularly applicable to multicentre trials in preschool children with CF and early or mild lung disease. This is the first article to collate the literature in this manner. This provides a rationale to support the use of BAL in early clinical trials in preschool children with CF. Review of the literature provides rationale to support the use of BAL in well-designed early-phase clinical trials in CF http://ow.ly/qGInZ
Perceptions of Speed and Risk: Experimental Studies of Road Crossing by Older People

Crossing a road safely is a complex task requiring good sensorimotor function and integration of information about traffic speed, distances and one’s own speed. Poor judgement through age-related sensorimotor or cognitive impairment or a predisposition to take risks could lead to errors with serious consequences. On a simulated road, 85 participants (age ≥70 years) were asked to cross in front of an approaching car with a clearance as small as considered safe in two conditions; (1) with nothing else to attend to (free crossing) and (2) with an additional ball-gathering task while waiting to cross (task crossing). Participants were categorised according to their crossing outcome (failed to cross, ‘hit’, exact, safe, cautious). Participants also performed two sub-studies; (1) the perception of the time-to-arrival of moving objects and (2) the perception of own gait speed. Physical and cognitive function and everyday risk-taking behaviour were also assessed. In free crossing, clearances varied but no participants were “hit” by the car. In task crossing, participants allowed smaller clearances and 10% of participants would have been hit while 13% missed the opportunity to cross altogether. Across a wide range of physical and cognitive measures, including perceived and actual gait speed, a consistent pattern was observed in the task crossing condition. The exact group performed best, the ‘hit’, safe and cautious groups performed less well while those who missed the opportunity (fail) performed worst. The exact group reported taking the greatest risks in everyday life whereas the remaining groups reported being cautious. In conclusion, we found older people with poorer perceptual, physical and cognitive function made inappropriate and risky decisions in a divided attention road-crossing task despite self-reports of cautious behaviour in everyday life.
The Marmoset Model of GB Virus B Infections: Adaptation to Host Phenotypic Variation

ABSTRACT Worldwide, approximately 170 million people are chronically infected with hepatitis C virus (HCV), and chronic infection frequently progresses to serious liver disease, including cirrhosis and hepatocellular carcinoma. GB virus B (GBV-B), the virus phylogenetically most closely related to HCV, causes hepatitis in tamarins. We have demonstrated the suitability of the tamarin as a host for GBV-B and as a surrogate nonhuman primate model for HCV infection, and we have initiated studies of GBV-B infection in a closely related species, the common marmoset (Callithrix jacchus). Here, we demonstrate that marmosets exhibit two phenotypes upon infection with GBV-B: the susceptible phenotype and the partially resistant phenotype. In addition, we identify changes that may correlate with adaptation of the virus to the partially resistant host. GBV-B was serially passaged five times through 14 marmosets as one lineage and two times through 6 marmosets as a second lineage. Virus adapted to the marmosets and eventually exhibited robust infections in two separate lineages, lineages 1 and 2. A third lineage was initiated with a molecular clone, and again, susceptible and partially resistant phenotypes were observed. Three isolates were fully sequenced (from lineage 1), and 21 nucleotide changes were observed, with six amino acid changes. We speculate that the marmoset partially resistant phenotype may be due to a polymorphism in the marmoset population that affects critical virus-host interactions and that wild-type GBV-B is capable of rapidly adapting to this altered host.
Functional Mapping of Human Learning: A Positron Emission Tomography Activation Study of Eyeblink Conditioning

Regional cerebral blood flow (rCBF) was measured using positron emission tomography during eyeblink conditioning in young adults. Subjects were scanned in three experimental conditions: delay conditioning, in which binaural tones preceded air puffs to the right eye by 400 msec; pseudoconditioning, in which presentations of tone and air puff stimuli were not correlated in time; and fixation rest, which served as a baseline control. Compared with fixation, pseudoconditioning produced rCBF increases in frontal and temporal cortex, basal ganglia, left hippocampal formation, and pons. Learning-specific activations were observed in conditioning as compared with pseudoconditioning in bilateral frontal cortex, left thalamus, right medial hippocampal formation, left lingual gyrus, pons, and bilateral cerebellum; decreases in rCBF were observed for bilateral temporal cortex, and in the right hemisphere in putamen, cerebellum, and the lateral aspect of hippocampal formation. Blood flow increased as the level of learning increased in the left hemisphere in caudate, hippocampal formation, fusiform gyrus, and cerebellum, and in right temporal cortex and pons. In contrast, activation in left frontal cortex decreased as learning increased. These functional imaging results implicate many of the same structures identified by previous lesion and recording studies of eyeblink conditioning in animals and humans and suggest that the same brain regions in animals and humans mediate multiple forms of associative learning that give meaning to a previously neutral stimulus.
Top-down contingent feature-specific orienting with and without awareness of the visual input

In the present article, the role of endogenous feature-specific orienting for conscious and unconscious vision is reviewed. We start with an overview of orienting. We proceed with a review of masking research, and the definition of the criteria of experimental protocols that demonstrate endogenous and exogenous orienting, respectively. Against this background of criteria, we assess studies of unconscious orienting and come to the conclusion that so far studies of unconscious orienting demonstrated endogenous feature-specific orienting. The review closes with a discussion of the role of unconscious orienting in action control.
The objective structured clinical examination: can physician‐examiners participate from a distance?

Currently, a ‘pedagogical gap’ exists in distributed medical education in that distance educators teach medical students but typically do not have the opportunity to assess them in large‐scale examinations such as the objective structured clinical examination (OSCE). We developed a remote examiner OSCE (reOSCE) that was integrated into a traditional OSCE to establish whether remote examination technology may be used to bridge this gap. The purpose of this study was to explore whether remote physician‐examiners can replace on‐site physician‐examiners in an OSCE, and to determine the feasibility of this new examination method.