Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypercholesterolemia attenuates angiogenesis but does not preclude augmentation by angiogenic cytokines.

BACKGROUND The impact of hyperlipidemia on collateral vessel development in vivo remains enigmatic. We sought to determine the anatomic extent and functional capacity of the collateral bed that develops in response to limb ischemia in a well characterized animal model of spontaneous hypercholesterolemia, the Watanabe heritable hyperlipidemic (WHHL) rabbit. We further characterized the impact of exogenous angiogenic cytokine administration on collateral vessel development and function in the same animal model. METHODS AND RESULTS Weight-matched 6-month-old male homozygous WHHL (n=9) and normal New Zealand White (NZW) (n=9) rabbits underwent surgical resection of one femoral artery. Ten days later, the ischemic hindlimb was evaluated for collateral vessel formation, blood flow, and tissue damage. Collateral vasculature was less extensive among WHHL than NZW, as indicated by a significant reduction in angiographic score (0.19+/-0.02 versus 0.35+/-0.03, P<.001) and capillary density (46.4+/-4.1 versus 78.9+/-4.6/mm2, P<.0002). This was associated with a reduction in calf blood pressure index (9.5+/-3.5% versus 32.8+/-2.8%, P<.0001), arterial blood flow (7.5+/-0.6 versus 13.6+/-0.7 mL/min, P<.0001), and muscle perfusion index (40.1+/-3.2% versus 65.9+/-2.0%, P<.0001) and an increase in muscle necrosis (48.16+/-5.41% versus 25.90+/-3.83% negative 2,3,5-triphenyltetrazolium chloride staining, P<.004). Treatment of WHHL rabbits (n=9) with recombinant human vascular endothelial growth factor produced a statistically significant improvement in all functional as well as anatomic indices of collateral development. CONCLUSIONS Collateral vessel development associated with hindlimb ischemia in vivo is severely attenuated in an animal model of spontaneous hypercholesterolemia but nevertheless may be augmented by administration of angiogenic cytokines.
Influence of Experience on the Thought Process of Clinical Psychologists: An Analysis from the Dual-Process Theories Framework

Abstract In the course of their work, psychologists must make judgments and complex decisions, skills that are part of clinical reasoning. Recent models approach the analysis of such process using the dual-process theories framework. This study provides an assessment of the two systems, System 1 and System 2, in forty-five clinical psychologists with different levels of experience (novices, intermediates and experts) with the purpose of exploring their level of activation and evolution throughout such stages of expertise. According to the results, clinical psychologists mainly activate System 2, M = 70.91, SD = 6.71, than System 1, M = 60.49, SD = 3.78; $ {F}_{\left(1,\kern0.5em 41\right)}=7.99;p<. 01;{\upeta}^2=. 163, $ when performing their clinical duties. However, no significant changes have been observed regarding the preferential use of thinking Systems 1 or 2 throughout the experience, both systems are used in a similar way in the different levels of expertise analyzed, with an increase of System 2 at the intermediate level of expertise. The results are analyzed in terms of intermediate effect and discussed focusing on the unremitting need for System 2 in psychologist work given the idiosyncratic characteristics of each case requiring treatment in the area of psychology and on the relationship of the two systems in clinical reasoning.
Analyse de séquences d'événements avec TraMineR

Les méthodes de fouille de motifs séquentiels fréquents ont donné lieu, depuis le travail fondateur de Agrawal et Srikant (1995), à un grand nombre de travaux de recherche. La librairie TraMineR pour l’environnement statistique R cherche à rendre ces méthodes accessibles aux chercheurs de divers domaines désirant analyser ou visualiser des ensembles de séquences d’événements. Il est à noter que TraMineR n’est pas adapté à l’étude d’une séquence unique d’événements. La librairie est disponible sur le CRAN (Comprehensive R Archive Network) et possède une aide en ligne ainsi qu’un manuel de l’utilisateur détaillé (Gabadinho et al., 2009). TraMineR offre les fonctionnalités pour séquences d’événements suivantes : – l’importation et la conversion de plusieurs formats de données et leur transformation en séquences d’événements, – l’extraction des motifs séquentiels fréquents, en prenant en compte des contraintes temporelles telles que le temps maximum entre deux événements ou la taille de la fenêtre, – le calcul de mesure de dissimilarité entre séquences d’événements afin de procéder, par exemple, à une classification non-supervisée des séquences (Studer et al., 2010) – l’identification des motifs séquentiels fréquents les plus discriminants par rapport à une autre variable d’intérêt en se basant sur des tests du χ de Pearson (Studer et al., 2010), – la visualisation des motifs séquentiels discriminant à l’aide des résidus,
Fibroblast-Like Synoviocytes of Mesenchymal Origin Express Functional B Cell-Activating Factor of the TNF Family in Response to Proinflammatory Cytokines1

Immunohistochemical analysis revealed that the intimal lining cells of synovial tissue of inflamed joints of patients with rheumatoid arthritis differed from that of normal joints or of diseased joints in osteoarthritis in that they stained with mAb specific for the B cell-activating factor of the TNF family (BAFF; also called BLyS). We generated fibroblast-like synoviocytes (FLS) cell lines that were bereft of myelomonocytic cells to examine whether mesenchymal-derived FLS could express this critical B cell survival factor. We found that FLS expressed low amounts of BAFF mRNA relative to that of myelomonocytic cells. However, when various cytokines/factors were added to such FLS cell lines, we found that IFN-γ or TNF-α were unique in that they could induce significant increases in BAFF mRNA and protein. Even minute amounts of IFN-γ primed FLS for TNF-α, allowing the latter to stimulate significantly higher levels of BAFF mRNA and protein than could TNF-α alone. Consistent with this, B cells cocultured with IFN-γ and/or TNF-α-treated FLS had a significantly greater viability than B cells cocultured with nontreated FLS. The enhanced protection of B cells afforded by IFN-γ/TNF-α-treated FLS was inhibited by the addition of BAFF-R:Fc fusion protein. We conclude that the proinflammatory cytokines IFN-γ and TNF-α can induce mesenchymal-derived FLS to express functional BAFF in vitro. The induced expression of BAFF on FLS by proinflammatory cytokines may enhance the capacity of such cells to protect B cells from apoptosis in inflammatory microenvironments in vivo.
uPAR (CD87) as a Biocompatibility Marker of Dialysis Membrane

Background/Aims: Hemodialysis (HD) therapy may lead to functional changes in patient leukocytes. For example, the upregulation of inflammatory cytokines, such as IL-1β and TNFα, has been well characterized. However, these findings do not explain the entire response of leukocytes in HD. In this study, we carried out a comprehensive gene expression analysis in leukocytes treated with various dialysis membranes using DNA microarrays. The identified gene has the potential to be a new marker for testing dialysis membrane biocompatibility. Methods: Gene expression profiles were compared between a group of leukocytes treated with various dialysis membranes and an untreated group by using DNA microarray analysis. Expression was confirmed by quantitative RT-PCR. The expression of the gene product (leukocyte surface protein) was examined in 20 chronic HD patients by flow cytometry. Results: In addition to the inflammatory cytokines, the urokinase plasminogen activator receptor (uPAR or CD87) gene was induced in leukocytes treated with each dialysis membrane. The extent of induction depended on the membrane’s material composition. The expression of the uPAR (CD87) protein on leukocytes was markedly increased in patients undergoing dialysis therapy. The magnitude of uPAR (CD87) protein expression was correlated with clinical findings, i.e., the degree of leukopenia and the expression of adhesion molecules. Conclusions: The gene and protein expression of uPAR (CD87) depended on the dialysis membrane material and correlated closely with clinical findings. These results suggest that uPAR has the potential to serve as a marker not only for clinical use but also for the development of new dialysis membranes.
Reliability of clinical findings and magnetic resonance imaging for the diagnosis of chondromalacia patellae.

BACKGROUND This diagnostic study was performed to determine the correlation between anterior knee pain and chondromalacia patellae and to define the reliability of magnetic resonance imaging for the diagnosis of chondromalacia patellae. METHODS Fifty-six young adults (median age, 19.5 years) with anterior knee pain had magnetic resonance imaging of the knee followed by arthroscopy. The patellar chondral lesions identified by magnetic resonance imaging were compared with the arthroscopic findings. RESULTS Arthroscopy confirmed the presence of chondromalacia patellae in twenty-five (45%) of the fifty-six knees, a synovial plica in twenty-five knees, a meniscal tear in four knees, and a femorotibial chondral lesion in four knees; normal anatomy was seen in six knees. No association was found between the severity of the chondromalacia patellae seen at arthroscopy and the clinical symptoms of anterior knee pain syndrome (p = 0.83). The positive predictive value for the ability of 1.0-T magnetic resonance imaging to detect chondromalacia patellae was 75% (95% confidence interval, 53% to 89%), the negative predictive value was 72% (95% confidence interval, 56% to 84%), the sensitivity was 60% (95% confidence interval, 41% to 77%), the specificity was 84% (95% confidence interval, 67% to 93%), and the diagnostic accuracy was 73% (95% confidence interval, 60% to 83%). The sensitivity was 13% (95% confidence interval, 2% to 49%) for grade-I lesions and 83% (95% confidence interval, 59% to 94%) for grade-II, III, or IV lesions. CONCLUSIONS Chondromalacia patellae cannot be diagnosed on the basis of symptoms or with current physical examination methods. The present study demonstrated no correlation between the severity of chondromalacia patellae and the clinical symptoms of anterior knee pain syndrome. Thus, symptoms of anterior knee pain syndrome should not be used as an indication for knee arthroscopy. The sensitivity of 1.0-T magnetic resonance imaging was low for grade-I lesions but considerably higher for more severe (grade-II, III, or IV) lesions. Magnetic resonance imaging may be considered an accurate diagnostic tool for identification of more severe cases of chondromalacia patellae.
LuxS-Based Signaling Affects Streptococcus mutans Biofilm Formation

ABSTRACT Streptococcus mutans is implicated as a major etiological agent in human dental caries, and one of the important virulence properties of this organism is its ability to form biofilms (dental plaque) on tooth surfaces. We examined the role of autoinducer-2 (AI-2) on S. mutans biofilm formation by constructing a GS-5 luxS-null mutant. Biofilm formation by the luxS mutant in 0.5% sucrose defined medium was found to be markedly attenuated compared to the wild type. Scanning electron microscopy also revealed that biofilms of the luxS mutant formed larger clumps in sucrose medium compared to the parental strain. Therefore, the expression of glucosyltransferase genes was examined and the gtfB and gtfC genes, but not the gtfD gene, in the luxS mutant were upregulated in the mid-log growth phase. Furthermore, we developed a novel two-compartment system to monitor AI-2 production by oral streptococci and periodontopathic bacteria. The biofilm defect of the luxS mutant was complemented by strains of S. gordonii, S. sobrinus, and S. anginosus; however, it was not complemented by S. oralis, S. salivarius, or S. sanguinis. Biofilm formation by the luxS mutant was also complemented by Porphyromonas gingivalis 381 and Actinobacillus actinomycetemcomitans Y4 but not by a P. gingivalis luxS mutant. These results suggest that the regulation of the glucosyltransferase genes required for sucrose-dependent biofilm formation is regulated by AI-2. Furthermore, these results provide further confirmation of previous proposals that quorum sensing via AI-2 may play a significant role in oral biofilm formation.
Three dimensional geo-tweet visualization system for spatio-temporal events

Geo-tweet visualization help users know the events that is happening over the space and time from the tweets or wikipedia while they click on the specified location for a 3D based tag visualization. Normal events are detected by system which happens anywhere or anytime using machine learning algorithm and special events are also extracted by comparing current situation to normal regularities. Generally, people look for location along with its route and information about surrounding tourist locations for which system provides spatial context of location which is being harvested from freely available source like wikipedia, Twitter, tumblr etc… Initially, Geo-referenced information are gathered which are closed to specified points and then gathered data is filtered based on frequency of words from data harvested, which is then visualized as a tag cloud in android mobile. Visualization details could be adjusted interactively based on interest of the client by changing radius of specified region. Visualization of tag cloud is then summarized to aid user to gain an overview of current situation that is happening over the time.
The firing of hippocampal place cells in the dark depends on the rat's recent experience

Hippocampal “place cells” fire when a freely moving rat is in a given location. The firing of these cells is controlled by visual and nonvisual environmental cues. The effects of darkness on the firing of place cells was studied using the task of Muller et al. (1987), in which rats were trained to chase randomly scattered food pellets in a cylindrical drum with a white cue-card attached to the wall. The position of the rats was tracked via an infrared LED on the headstage with a video system linked to computer. Two experimental protocols were used: in the first, lights were turned off after the rat had already been placed in the chamber; in the second, the rat was placed in the darkened chamber. The dark segments produced by these 2 methods were identical with respect to light and other cues but differed with respect to the rat's experience. The firing patterns of 24 of 28 cells were unaffected by darkness when it was preceded by a light period. In contrast, the firing patterns of 14 of 22 cells changed dramatically when the rats were put into the darkened chamber. Furthermore, the majority of cells that changed their firing pattern in initial darkness maintained that change when the lights were turned on. These results show that place cells can fire differently in identical cue situations and that the best predictor of firing pattern is a combination of current cues and the rat's recent experience. The results are discussed in terms of mnemonic properties of hippocampal cells and “remapping” of place cell representations.
A Two-Way Direct Control of Central Air-Conditioning Load Via the Internet

A novel real-time optimization approach for two-way direct load control (TWDLC) of central air-conditioning chillers is proposed. For TWDLC, the main computer in the control center constantly monitors the average controllable load of every customer. For real-time calculations, a computationally fast and effective approach based on linear programming is proposed to determine the shedding ratio of every customer. The proposed optimization approach will minimize the difference between the load required to shed and the load actually shed at each sampling interval. Every customer's contribution to the load shedding is also leveled by the proposed approach. A gateway is installed at every customer's site to coordinate shedding control with the main computer through the Internet. As soon as the gateway receives the expected shedding ratio, it calculates the load required to shed and coordinates all chiller units in operation to conduct load shedding, thereby achieving the load reduction amount.
The mechanism of oxidative damage in the nephrotoxicity of mice caused by nano-anatase TiO2

While the nephrotoxicity of high-dose nano-TiO2 has been demonstrated, very little is known about the mechanism of oxidative stress to the animal kidney. In order to understand the nephrotoxicity of nano-anatase TiO2 particles, various biochemical and chemical parameters were assayed in mouse kidneys. Abdominal exposures of high-dose nano-anatase TiO2 caused nephritis and oxidative stress to kidney. An increase in coefficients of the kidney, Ti accumulation and histopathological changes in kidney could be observed, followed by increased reactive oxygen species generation and lipid peroxidation, and decreased activities of superoxide dismutase, catalase, ascorbate peroxidase and total antioxidant capacity as well as antioxidants such as glutathione and ascorbic acid content. In addition, kidney functions were disrupted, including increase of the creatinine, calcium and phosphonium, and reduction of uric acid and blood urea nitrogen. Our results suggest that nephritis generation in mice caused by nano-anatase TiO2 particles is closely related to oxidative stress.
Fatigue in multiple sclerosis: The contribution of occult white matter damage

Background: A functional cortico-subcortical disconnection has been recognized in fatigued multiple sclerosis (MS) patients. Normal appearing white matter (NAWM) damage might contribute to the abovementioned disconnectivity. Objectives: To assess the relationship between fatigue and microstructural NAWM damage in relapsing-remitting (RR) MS. Methods: Sixty RRMS patients and 29 healthy controls (HC) underwent a magnetic resonance imaging (MRI) protocol including diffusion tensor imaging (DTI). Patients with a mean Fatigue Severity Scale (FSS) score ⩾ 4 were considered fatigued (fatigued MS (F-MS)). Tract-based spatial statistics were applied for voxel-wise analysis of DTI indices. A correlation analysis was performed between FSS score and DTI indices in the entire MS group. Results: Thirty MS patients were F-MS. Compared to HC, F-MS patients showed a more extensive NAWM damage than not fatigued MS (NF-MS) patients, with additional damage in the following tracts: frontal and occipital juxtacortical fibers, external capsule, uncinate fasciculus, forceps minor, superior longitudinal fasciculus, cingulum, and pons. No differences were found between F-MS and NF-MS patients. Fatigue severity correlated to DTI abnormalities of corona radiata, cingulum, corpus callosum, forceps minor, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamus and anterior thalamic radiation, cerebral peduncle, and midbrain. Conclusions: Fatigue is associated to a widespread microstructural NAWM damage, particularly in associative tracts connected to frontal lobes.
Molecular Mechanism of MBX2319 Inhibition of Escherichia coli AcrB Multidrug Efflux Pump and Comparison with Other Inhibitors

ABSTRACT Efflux pumps of the resistance nodulation division (RND) superfamily, such as AcrB, make a major contribution to multidrug resistance in Gram-negative bacteria. The development of inhibitors of the RND pumps would improve the efficacy of current and next-generation antibiotics. To date, however, only one inhibitor has been cocrystallized with AcrB. Thus, in silico structure-based analysis is essential for elucidating the interaction between other inhibitors and the efflux pumps. In this work, we used computer docking and molecular dynamics simulations to study the interaction between AcrB and the compound MBX2319, a novel pyranopyridine efflux pump inhibitor with potent activity against RND efflux pumps of Enterobacteriaceae species, as well as other known inhibitors (D13-9001, 1-[1-naphthylmethyl]-piperazine, and phenylalanylarginine-β-naphthylamide) and the binding of doxorubicin to the efflux-defective F610A variant of AcrB. We also analyzed the binding of a substrate, minocycline, for comparison. Our results show that MBX2319 binds very tightly to the lower part of the distal pocket in the B protomer of AcrB, strongly interacting with the phenylalanines lining the hydrophobic trap, where the hydrophobic portion of D13-9001 was found to bind by X-ray crystallography. Additionally, MBX2319 binds to AcrB in a manner that is similar to the way in which doxorubicin binds to the F610A variant of AcrB. In contrast, 1-(1-naphthylmethyl)-piperazine and phenylalanylarginine-β-naphthylamide appear to bind to somewhat different areas of the distal pocket in the B protomer of AcrB than does MBX2319. However, all inhibitors (except D13-9001) appear to distort the structure of the distal pocket, impairing the proper binding of substrates.
Comparison of the Physical and Sensory Properties of Hybrid Citrus Fruit Jaffa® Sweetie in Relation to the Parent Fruits

In the presented study, an overall Jaffa sweetie evaluation was made to find a correlation between Citrus grandis Osbeck × Citrus paradisi Macf. and its parent fruits’ (Citrus grandis Osbeck, Citrus paradisi Macf.) properties. Based on the sensory analysis, it was found that the taste and aroma of the new hybrid fruit are close to pummelo. By the use of chromatographic analysis, the selected monoterpenes present in the fruits were quantified. α-terpineol was typed as the main monoterpene compound in the headspace of sweetie and grapefruit, with the concentrations: 20.96 and 87.9 μg/g, respectively. In turn, γ-terpinene was chosen as the most important monoterpene determining the flavor of sweetie fruit. Based on two-dimensional gas chromatography (GC × GC-TOF-MS) and principal component analysis (PCA) of the data, several volatile compounds were associated with analyzed fruits’ aroma. Jaffa Sweetie is the hybrid fruit with sensory properties similar to pummelo with a higher content of monoterpenes, which improves its health benefits compared to the parent fruit. The research presents an instrumental method for assessing the aroma properties of the fruit as a reference method for sensory analysis, commonly used in the industry.
Higher naloxone dosing in a quantitative systems pharmacology model that predicts naloxone-fentanyl competition at the opioid mu receptor level

Rapid resuscitation of an opioid overdose with naloxone, an opioid antagonist, is critical. We developed an opioid receptor quantitative systems pharmacology (QSP) model for evaluation of naloxone dosing. In this model we examined three opioid exposure levels that have been reported in the literature (25 ng/ml, 50 ng/ml, and 75 ng/ml of fentanyl). The model predicted naloxone-fentanyl interaction at the mu opioid receptor over a range of three naloxone doses. For a 2 mg intramuscular (IM) dose of naloxone at lower fentanyl exposure levels (25 ng/ml and 50 ng/ml), the time to decreasing mu receptor occupancy by fentanyl to 50% was 3 and 10 minutes, respectively. However, at a higher fentanyl exposure level (75 ng/ml), a dose of 2 mg IM of the naloxone failed to reduce mu receptor occupancy by fentanyl to 50%. In contrast, naloxone doses of 5 mg and 10 mg IM reduced mu receptor occupancy by fentanyl to 50% in 5.5 and 4 minutes respectively. These results suggest that the current doses of naloxone (2 mg IM or 4 mg intranasal (IN)) may be inadequate for rapid reversal of toxicity due to fentanyl exposure and that increasing the dose of naloxone is likely to improve outcomes.