Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacology of losartan, an angiotensin II receptor antagonist, in animal models of hypertension

Background: Clinical experience with angiotensin converting enzyme (ACE) inhibitors has shown that inhibition of the renin–angiotensin system is effective therapy for hypertension and heart failure. Losartan (DuP753, MK954, cozaar) is the first non-peptidic drug that inhibits the renin-angiotensin system by selectively blocking the interaction of angiotensin II with its receptor Differences between losartan and ACE inhibitors: Pharmacological differences between ACE inhibitors and losartan could affect comparative efficacy and/or safety. In addition to angiotensin I, ACE has other substrates (e.g. kinins). Blocking the metabolism of kinins with ACE inhibitors could be beneficial (e.g. vasodilation) and/or elicit side effects (e.g. cough) which will not be produced by losartan. Non-ACE pathways of angiotensin II formation have been described (e.g. angiotensin I convertase) which may limit the ability of ACE inhibitors to prevent formation of angiotensin II in all tissues. Losartan blocks angiotensin II responses irrespective of the route or site of angiotensin II formation. Two binding sites for angiotensin II are widely accepted, AT1 and AT2. Losartan blocks only AT1 sites while ACE inhibitors functionally block angiotensin II interaction with both sites. Since the physiological role for AT2 sites is unknown, the relevance of this difference between ACE inhibitors and losartan is questionable Hypertension: In animal models of hypertension, the efficacy of losartan is equivalent to the efficacy of ACE inhibitors. In animal models that reflect complications of hypertension, such as kidney dysfunction, cardiac and vascular hypertrophy and stroke, losartan and ACE inhibitors are also equally effective. From these results, kinin potentiation and lack of inhibition of angiotensin I convertase do not lead to differences in pharmacological efficacy between ACE inhibitors and losartan. Therefore, with respect to therapeutic efficacy, results in animal models indicate that losartan will display the beneficial pharmacology of ACE inhibitors without the detrimental side effects attributed to kinin potentiation
Recent advances in neuropathology, biomarkers and therapeutic approach of multiple system atrophy

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterised by a variable combination of autonomic failure, levodopa-unresponsive parkinsonism, cerebellar ataxia and pyramidal symptoms. The pathological hallmark is the oligodendrocytic glial cytoplasmic inclusion (GCI) consisting of α-synuclein; therefore, MSA is included in the category of α-synucleinopathies. MSA has been divided into two clinicopathological subtypes: MSA with predominant parkinsonism and MSA with predominant cerebellar ataxia, which generally correlate with striatonigral degeneration and olivopontocerebellar atrophy, respectively. It is increasingly recognised, however, that clinical and pathological features of MSA are broader than previously considered. In this review, we aim to describe recent advances in neuropathology of MSA from a review of the literature and from information derived from review of nearly 200 definite MSA cases in the Mayo Clinic Brain Bank. In light of these new neuropathological findings, GCIs and neuronal cytoplasmic inclusions play an important role in clinicopathological correlates of MSA. We also focus on clinical diagnostic accuracy and differential diagnosis of MSA as well as candidate biomarkers. We also review some controversial topics in MSA. Cognitive impairment, which has been a non-supporting feature of MSA, is considered from both clinical and pathological perspectives. The cellular origin of α-synuclein in GCI and a ‘prion hypothesis’ are discussed. Finally, completed and ongoing clinical trials targeting disease modification, including immunotherapy, are summarised.
Central Role for MyD88 in the Responses of Microglia to Pathogen-Associated Molecular Patterns1

Microglia, the innate immune effector cells of the CNS parenchyma, express TLR that recognize conserved motifs of microorganisms referred to as pathogen-associated molecular patterns (PAMP). All TLRs identified to date, with the exception of TLR3, use a common adaptor protein, MyD88, to transduce activation signals. Recently, we reported that microglial activation in response to the Gram-positive bacterium Staphylococcus aureus was not completely attenuated following TLR2 ablation, suggesting the involvement of additional receptors. To assess the functional role of alternative TLRs in microglial responses to S. aureus and its cell wall product peptidoglycan as well as the Gram-negative PAMP LPS, we evaluated primary microglia from MyD88 knockout (KO) and wild-type mice. The induction of TNF-α, IL-12 p40, and MIP-2 (CXCL2) expression by S. aureus- and peptidoglycan-stimulated microglia was MyD88 dependent, as revealed by the complete inhibition of cytokine production in MyD88 KO cells. In addition, the expression of additional pattern recognition receptors, including TLR9, pentraxin-3, and lectin-like oxidized LDL receptor-1, was regulated, in part, via a MyD88-dependent manner as demonstrated by the attenuated expression of these receptors in MyD88 KO microglia. Microglial activation was only partially inhibited in LPS-stimulated MyD88 KO cells, suggesting the involvement of MyD88-independent pathways. Collectively, these findings reveal the complex mechanisms for microglia to respond to diverse bacterial pathogens, which occur via both MyD88-dependent and -independent pathways.
Importance of Si-N atomic configuration at the Si/oxynitride interfaces on the performance of scaled MOSFETs

This paper reports the studies on the inversion-layer mobility in n-MOSFETs having N/sub 2/O- and NO-based oxynitrided gate oxides. Different behavior on the effective normal field (E/sub eff/) dependence have been found between N/sub 2/Oand NO-based oxynitrided samples. It has been found that the positioning of O-Si-N bonds slightly inner from the interface leads to higher Id in NO-samples than N/sub 2/O-samples. This improvement of Id takes place through two mechanisms. One is less surface roughness scattering due to smoother interface and the other is less Coulomb scattering probability due to remote interaction with inversion carriers.
Long-interval T 2 w subtraction MRI : A powerful new outcome measure in MS trials Running Head : T 2 w subtraction MR imaging in phase II MS trials

1 Department of Radiology, 2 Department of Epidemiology and Biostatistics, 3 Department of Pathology, 4 Department of Physics and Medical Technology, 5 Department of Informatics, 6 Department of Neurology, MS Center Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. Center for Neurological Imaging, Departments of Radiology and Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA
Machine Learning for Recommendation System

Recommendation system has been seen to be very useful for user to select an item amongst many. Most existing recommendation systems rely either on a collaborative approach or a content-based approach to make recommendations. We have applied machine learning techniques to build recommender systems. We have taken two approaches. In the first approach a content based recommender system is built, which uses collaborative data, so that it gets the effect of a hybrid approach to get better result of recommendation. Attributes used for content based recommendations are assigned weights depending on their importance to users. The weight values are estimated from a set of linear regression equations obtained from a social network graph which captures human judgment about similarity of items. In the second approach agent of call centre have been recommended some procedure depending on the current state of online call. A combination of K-Means Algorithm and Hidden Markov model is used.
Perfluorooctane sulfonate in fish-eating water birds including bald eagles and albatrosses.

Perfluorooctane sulfonate (PFOS) was measured in 161 samples of liver, kidney, blood, or egg yolk from 21 species of fish-eating water birds collected in the United States including albatrosses from Sand Island, Midway Atoll, in the central North Pacific Ocean. Concentrations of PFOS in the blood plasma of bald eagles collected fromthe midwestern United States ranged from 13 to 2,220 ng/mL (mean: 330 ng/mL), except one sample that did not contain quantifiable concentrations of PFOS. Concentrations of PFOS were greater in blood plasma than in whole blood. Among 82 livers from various species of birds from inland or coastal U.S. locations, Brandt's cormorant from San Diego, CA, contained the greatest concentration of PFOS (1,780 ng/g, wet wt). PFOS was also found in the sera of albatrosses from the central North Pacific Ocean at concentrations ranging from 3 to 34 ng/mL. Occurrence of PFOS in birds from remote marine locations suggests widespread distribution of PFOS and related fluorochemicals in the environment.
Research on the Application of O2O E-Commerce in the New Rural Agricultural Construction of HuNan Province

This paper expounded the citrus industry development of ShiMen county,analyzed the current problems in the citrus industry development of ShiMen according to the investigating data,explored the application in the citrus industry depending on newly 020 E-commence pattern,and solved the bottleneck in the citrus industry development of ShiMen through the online-offline linkage interaction. It will accelerate the development of the new countryside construction in HuNan province.
Alternative complement pathway-mediated lysis of measles virus infected cells: induction by IgG antibody bound to individual viral glycoproteins and comparative efficacy of F(ab')2 and Fab' fragments.

Lysis of measles virus-infected cells by human serum is dependent on IgG antibody and an intact alternative complement pathway. The binding sites of IgG measles virus antibody, or its fragments, on the surface of measles virus-infected cells were determined by cell surface radioiodination and immunoprecipitation. It was found that IgG bound to either of the two measles virus surface glycoproteins was effective in inducing cell lysis by the alternative pathway. Thus, IgG bound only to the viral hemagglutinin (HA) or only to the fusion protein (F) could induced lysis in C4-depleted human serum; the same number of IgG molecules bound to either HA or F induced equivalent dose-related lysis. Divalent antibody bound preferentially to HA on the surface of intact cells; this enabled antibody to F to be obtained free of antibody to HA by adsorption. Quantitative studies of binding and lysis showed that lysis of measles virus-infected cells by whole or C4-depleted serum required binding of at least 10 times more Fab′ than F(ab′)2 or IgG molecules per cell. In these experiments, C4-depleted serum was quantitatively and kinetically equivalent to whole serum in mediating lysis of measles-infected cells. Hence, the binding of IgG to either of the two measles viral polypeptides (HA, F) expressed on the surface of infected cells induces lysis by the alternative pathway, and there is a clear requirement for divalency for effective induction of lysis.
CPW-Fed Planar Printed Monopole Antenna With Impedance Bandwidth Enhanced

A coplanar waveguide (CPW)-fed monopole antenna is proposed, which is composed of a rectangular monopole patch notched at the bottom, a T-shaped CPW ground in the notch, and a tapered CPW ground out of the notch. The simulated and experimental results show that the antenna achieves a fractional impedance bandwidth of 164% for S11 ¿ -10 dB, which is about 2.3 times of the conventional one. The parametric studies and measured radiation characteristics are presented. The results show that the antenna exhibits good characteristics and is suitable for portable mobile ultrawideband (UWB) applications.
APPRAISAL OF ETHNOBOTANICAL USES OF THE WETLAND PLANTS OF PUNJAB, PAKISTAN

The present study was carried out during the years 2008-2011 to document the ethnobotanical data on the traditional uses of Punjab, Pakistan. The data included local name, habit and habitat of these plants with special emphasis on their therapeutic uses against different human ailments. Various visits of the study area were made to interview the local elderly, knowledgeable people and herbal healers. A total of eighteen aquatic and semi-aquatic plants belonging to three monocotyledonous and fourteen dicotyledonous families were reported, having medicinal and food value as well as the uses making ropes, mats, baskets and as soil binders and ornamentals.Background: Aquatic and semiaquatic plants have a multiplicity of traditional and ethnopharmacological uses ranging from medicinal, famine food to fodder and others. Therefore, the present study was carried out during the years 2008-2011 to document the locally used medicinal, ethnobotanical and traditional data of aquatic and semiaquatic plants of the Punjab, Pakistan. Material and Method: Various visits of the study area were made to collect the data of these plants included local name, habit and habitat with special emphasis on their therapeutic uses against different human ailments. The local elderly, knowledgable people and herbal healers were also interviewed during the visits. Results: A total of thirty-four aquatic and semiaquatic plants were collected and out of these, eighteen plants belonging to the three monocotyledonous and fourteen dicotyledonous families were reported to medicinal and food value as well as found useful in making ropes, mats, baskets and soil binding. Conclusion: The wetland of Punjab (Pakistan) possesses a variety of medicinal plants that are being utilized against various human diseases, e.g. Respiratorical, dermatological, gastrontological, neurological and cardio-vascular diseases.
The effectiveness of dementia care mapping in intellectual disability residential services

This article is presented as a follow-up to exploratory work published in this journal in 2001. It describes a study that aimed to assess the effectiveness of dementia care mapping in supporting practice improvement in intellectual disability residential services. An average of 9 hours of observational data was collected using dementia care mapping in relation to 14 adults with severe or profound intellectual disabilities. Sixteen interviews were also undertaken with staff over a 4 month period.The findings provided a detailed picture of the activities and interactions between the participants involved in the study and raised some issues about ‘organizational culture’ when developing person-centred approaches.They have helped strengthen the case that care mapping has the potential to be a useful addition to the existing repertoire of tools to support effective practice improvement and person-centred planning.
Photochemical Modeling in California with Two Chemical Mechanisms: Model Intercomparison and Response to Emission Reductions

ABSTRACT An updated version of the Statewide Air Pollution Research Center (SAPRC) chemical mechanism (SAPRC07C) was implemented into the Community Multiscale Air Quality (CMAQ) version 4.6. CMAQ simulations using SAPRC07C and the previously released version, SAPRC99, were performed and compared for an episode during July– August, 2000. Ozone (O3) predictions of the SAPRC07C simulation are generally lower than those of the SAPRC99 simulation in the key areas of central and southern California, especially in areas where modeled concentrations are greater than the federal 8-hr O3 standard of 75 parts per billion (ppb) and/or when the volatile organic compound (VOC)/nitrogen oxides (NOx) ratio is less than 13. The relative changes of ozone production efficiency (OPE) against the VOC/NOx ratio at 46 sites indicate that the OPE is reduced in SAPRC07C compared with SAPRC99 at most sites by as much as approximately 22%. The SAPRC99 and SAPRC07C mechanisms respond similarly to 20% reductions in anthropogenic VOC emissions. The response of the mechanisms to 20% NOx emissions reductions can be grouped into three cases. In case 1, in which both mechanisms show a decrease in daily maximum 8-hr O3 concentration with decreasing NOx emissions, the O3 decrease in SAPRC07C is smaller. In case 2, in which both mechanisms show an increase in O3 with decreasing NOx emissions, the O3 increase is larger in SAPRC07C. In case 3, SAPRC07C simulates an increase in O3 in response to reduced NOx emissions whereas SAPRC99 simulates a decrease in O3 for the same region. As a result, the areas where NOx controls would be disbeneficial are spatially expanded in SAPRC07C. Although the results presented here are valuable for understanding differences in predictions and model response for SAPRC99 and SAPRC07C, the study did not evaluate the impact of mechanism differences in the context of the U.S. Environmental Protection Agency's guidance for using numerical models in demonstrating air quality attainment. Therefore, additional study is required to evaluate the full regulatory implications of upgrading air quality models to SAPRC07. IMPLICATIONS CMAQ simulations of gas-phase pollutants over California were conducted using the newly released SAPRC07C gas-phase chemical mechanism and the previous released version, SAPRC99. SAPRC07C predicted slightly lower concentrations of O3 and important radical species than did SAPRC99 in key polluted regions of California. In certain regions, SAPRC07C simulates an increase in O3 in response to 20% reductions in NOx emissions, whereas SAPRC99 simulates a decrease in O3. A consequence of this difference is that areas where NOx controls would be disbeneficial are spatially expanded for SAPRC07C compared with SAPRC99.
Implementation of clustering of uncertain data on probability distribution similarity

— Clustering on uncertain data, one of the essential tasks in mining uncertain data, posts significant challenges on both modeling similarity between uncertain objects and developing efficient computational methods. The previous methods extend traditional partitioning clustering methods like k-means and density-based clustering methods like DBSCAN to uncertain data, thus rely on geometric distances between objects. Such methods cannot handle uncertain objects that are geometrically indistinguishable, such as products with the same mean but very different variances in customer ratings. Surprisingly, probability distributions, which are essential characteristics of uncertain objects, have not been considered in measuring similarity between uncertain objects. In this project, we systematically model uncertain objects in both continuous and discrete domains, where an uncertain object is modeled as a continuous and discrete random variable, respectively. We use the well-known Kullback-Leibler divergence to measure similarity between uncertain objects in both the continuous and discrete cases, and integrate it into partitioning and density-based clustering methods to cluster uncertain objects.
Mediated Generalization of the Effect of Reprimands Across Two Topographies of Self-Injury

This study sought to assess the effects of pairing a neutral stimulus with a reprimand contingent on occurrences of two topographies of problem behavior. Using a multiple baseline withdrawal with a nested multi-element design, contingencies were first applied to eye poking and, subsequently, to a second behavior, skin picking. In each case, the participant wore wristbands (a previously neutral stimulus) during treatment sessions. Results indicated that the reprimands were effective in decreasing both behaviors. In addition, when skin picking resulted in reprimands, eye poking also decreased. However, when reprimands were contingent on eye-poking, the effects did not appear to generalize to skin-picking. Some possible accounts for this asymmetrical pattern of generalization are discussed.
Wnt5a participates in hepatic stellate cell activation observed by gene expression profile and functional assays.

AIM To identify differentially expressed genes in quiescent and activated hepatic stellate cells (HSCs) and explore their functions. METHODS HSCs were isolated from the normal Sprague Dawley rats by in suit perfusion of collagenase and pronase and density Nycodenz gradient centrifugation. Total RNA and mRNA of quiescent HSCs, and culture-activated HSCs were extracted, quantified and reversely transcripted into cDNA. The global gene expression profile was analyzed by microarray with Affymetrix rat genechip. Differentially expressed genes were annotated with Gene Ontology (GO) and analyzed with Kyoto encyclopedia of genes and genomes (KEGG) pathway using the Database for Annotation, Visualization and Integrated Discovery. Microarray data were validated by quantitative real-time polymerase chain reaction (qRT-PCR). The function of Wnt5a on human HSCs line LX-2 was assessed with lentivirus-mediated Wnt5a RNAi. The expression of Wnt5a in fibrotic liver of a carbon tetrachloride (CCl(4))-induced fibrosis rat model was also analyzed with Western blotting. RESULTS Of the 28 700 genes represented on this chip, 2566 genes displayed at least a 2-fold increase or decrease in expression at a P < 0.01 level with a false discovery rate. Of these, 1396 genes were upregulated, while 1170 genes were downregulated in culture-activated HSCs. These differentially expressed transcripts were grouped into 545 GO based on biological process GO terms. The most enriched GO terms included response to wounding, wound healing, regulation of cell growth, vasculature development and actin cytoskeleton organization. KEGG pathway analysis revealed that Wnt5a signaling pathway participated in the activation of HSCs. Wnt5a was significantly increased in culture-activated HSCs as compared with quiescent HSCs. qRT-PCR validated the microarray data. Lentivirus-mediated suppression of Wnt5a expression in activated LX-2 resulted in significantly impaired proliferation, downregulated expressions of type I collagen and transforming growth factor-β1. Wnt5a was upregulated in the fibrotic liver of a CCl(4)-induced fibrosis rat model. CONCLUSION Wnt5a is involved in the activation of HSCs, and it may serve as a novel therapeutic target in the treatment of liver fibrosis.
Substrate-Guided Ablation of Ischemic Ventricular Tachycardia: Is itReally Necessary to Induce Ventricular Tachycardia to be Successful?

Traditionally, catheter ablation of ventricular tachycardia (VT) consists of mapping the circuit during VT, and using pacing maneuvers to localize critical isthmus of the circuit. However, substrate-guided ablation of VT is a relatively new technique and involves identifying potentially arrhythmogenic regions of myocardium in sinus rhythm and avoids the need for mapping during VT. In this short editorial article, we aimed to discuss substrate mapping of VT.