gebhart/patrepeval huggingface dataset:
<i>In Silico</i> Prediction of Drug Side Effects (2015)

Established drugs frequently lack selectivity, and a third to half of research compounds in pharmacological databases are reported to be promiscuous. Correspondingly, attempts to predict adverse drug reactions (ADRs) must take multitarget drug activity into account. Systems pharmacology approaches do so by combining systems biology with chemoinformatic inference to investigate how molecular interactions drive whole-body outcomes. These multiscale models form networks of target perturbation and biological effect that, when organized into layers of increasing complexity, comprise the drug response of a binding site, cell, tissue, organ, or entire patient in the clinic.Systems pharmacology's application to the prediction of antitarget-mediated side effects is the focus of this chapter. In broad strokes, we consider in silico methods to predict drug off-target activity from a chemocentric perspective and then turn to the analysis of off-targets as antitargets and the means by which we may associate specific side effects with them.To address this, we survey current techniques in the systematic inference of drug off-targets, such as the Similarity Ensemble Approach (SEA). These target predictions, when taken together across collections of drugs and drug-like molecules, may be organized into global pharmacological networks linking small molecules to their known and putative protein targets.Drug-to-target networks serve as a foundation for multiscale models incorporating the more complex phenotypic, disease, and ADR outcomes we ultimately seek to predict. However, the associations known between protein targets and the biological outcomes of their modulation are at times surprisingly tenuous. Whereas certain antitargets, such as the hERG channel, are well accepted, it is far from clear how one might comprehensively ask what antitarget role an arbitrary target plays, much less whether certain targets are only antitargets when perturbed together. This chapter consequently addresses the means by which off-targets might be sifted for antitargets.Looking forward, a long-standing limitation in the annotation of ADRs to new antitargets has been the inability to perform forward chemical and genetic perturbations confirming these mechanistic hypotheses in sufficiently relevant models of human patients. One approach to this, complementary to computational models, has been the emergence of rapid, whole-organism and cell-based model systems tractable to genetic perturbation that can be assayed for quantitative phenotypic readouts. The chapter thus concludes with a consideration of the current advances, challenges, and opportunities in the generation and analysis of these phenotypic data, including their use within the broader systems pharmacology context introduced at its beginning.
Comments: Rights of the Maryland Probationer: A Primer for the Practitioner (1982)

Until relatively recently, persons placed on probation were denied even the most basic of due process protections. Beginning in the late 1960's, a series of Supreme Court decisions made it clear that many of the rights afforded the average citizen were equally applicable to the probationer. Since that time the rights afforded the Maryland probation have expanded greatly. This comment presents the current state of those rights and its author concludes that although burdened by many restrictions, the Maryland probationer is nonetheless in an advantageous position when compared with his counterpart in other jurisdictions.
Live or computerized simulation of clinical encounters: Do clinicians work up patient cases differently? (2006)

Computer simulation of clinical encounters is increasingly used in clinical settings to train patient work-up. The aim of this prospective, controlled study was to compare the characteristics of data collection and diagnostic exploration of physicians working up cases with a standardized patient and in a computerized simulation. Six clinicians of different clinical experience in internal medicine worked up three cases with a standardized patient and through a computer simulation allowing free inquiry. After each encounter, we asked the subjects to justify the information collected and to comment on their working diagnoses. The characteristics of data collected and working diagnoses generated were assessed and compared, according to the simulation method used. In the computer simulation, physicians limited their data collection and focused earlier and more specifically on information and working diagnoses with high levels of relevance. They reached a similar diagnostic accuracy and made decisions of a similar relevance. Computer simulation with a free-inquiry approach reproduces the data collection and the diagnostic exploration observed in a standardized-patient simulation and promotes an early collection of relevant data. Its contribution to extend the competence of learners in clinical settings should be further evaluated.
Modified lymphocyte response to mitogens after intraperitoneal injection of glycopeptidolipid antigens from Mycobacterium avium complex (1988)

Intraperitoneal injection of glycopeptidolipid (GPL) antigens from Mycobacterium avium complex serovar 4 resulted in the decreased ability of murine splenic lymphocytes to respond to nonspecific-mitogen-induced blastogenesis when exposed to concanavalin A, phytohemagglutinin, and lipopolysaccharide. Adherent cell depletion and cell mixing experiments with T lymphocytes indicated that macrophages were not a major contributor to the immunosuppression observed in this study. Enumeration of splenic lymphocytes by means of flow-cytometry with fluorescein isothiocyanate-conjugated monoclonal antibodies demonstrated that intraperitoneal injection of GPL antigens resulted in a significant decrease in Thy-1+ and Lyt-1+ cells but no change in the numbers of Lyt-2+ cells. Treatment with GPL antigens in vitro affected the ability of splenic mononuclear cells to respond optimally for concanavalin A-induced blastogenesis at 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml and lipopolysaccharide-induced blastogenesis at concentrations ranging from 5 to 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml. However, in vitro treatment with GPL antigens did not affect phytohemagglutinin-induced blastogenesis at concentrations ranging from 5 to 40 micrograms of GPL per 4 X 10(5) cells per 0.2 ml. These findings suggest that GPL antigens or their metabolites affect lymphocyte function and may be important cofactors in the overall pathogenesis of M. avium complex infections.
Kerala Pioneering Pediatric Surgery in India (2014)

Pediatric surgeons of Kerala are very proud to have led the development of superspeciality in any branch of medicine in Kerala and also superspeciality of Pediatric surgery in whole of India. Late Prof. Raman Nair returned in 1954 after training under Dr. Everett Koop in US. Same year, in his far-sighted vision for future development of the speciality, he moved to SATH, Medical College, Trivandrum and started Pediatric surgery as a speciality attached to Paediatrics department; this was the beginning of Pediatric surgery in India. He opted for Pediatric surgery as a full time job and did not do any general surgery work in adults. He was the first full time Pediatric surgeon of India; during the next few years, 2 surgeons, one in Calcutta, Prof. UC Chakraboty and Prof. D Anjaneyulu in Hyderabad started working as full time Pediatric surgeons. In Mumbai, Delhi and Chennai, Pediatric surgery developed much later and then all over the country.
Biomimetic Arrays of Oriented Helical ZnO Nanorods and Columns (2002)

Extended helical or chiral nanostructures are usually associated with biomolecules but are mostly absent in synthetic materials. Here we report the first synthesis of unusual oriented and extended helical nanostructures in synthetic ceramics. Large arrays of oriented helical ZnO nanorods and columns are formed using simple citrate ions to control the growth habits of the ZnO crystal. This novel mechanism could lead to new approaches to control the orientation, the surface area, and the defect structure of synthetic materials that are critical for practical applications. The morphology generated in the helical ZnO nanostructure shows remarkable resemblance to the growth morphology of nacreous calcium carbonate and thus may shed new light on morphology and orientation control of biominerals.
Nutrient-dependent regulation of autophagy through the target of rapamycin pathway (2009)

In response to nutrient deficiency, eukaryotic cells activate macroautophagy, a degradative process in which proteins, organelles and cytoplasm are engulfed within unique vesicles called autophagosomes. Fusion of these vesicles with the endolysosomal compartment leads to breakdown of the sequestered material into amino acids and other simple molecules, which can be used as nutrient sources during periods of starvation. This process is driven by a group of autophagy-related (Atg) proteins, and is suppressed by TOR (target of rapamycin) signalling under favourable conditions. Several distinct kinase complexes have been implicated in autophagic signalling downstream of TOR. In yeast, TOR is known to control autophagosome formation in part through a multiprotein complex containing the serine/threonine protein kinase Atg1. Recent work in Drosophila and mammalian systems suggests that this complex and its regulation by TOR are conserved in higher eukaryotes, and that Atg1 has accrued additional functions including feedback regulation of TOR itself. TOR and Atg1 also control the activity of a second kinase complex containing Atg6/Beclin 1, Vps (vacuolar protein sorting) 15 and the class III PI3K (phosphoinositide 3-kinase) Vps34. During autophagy induction, Vps34 activity is mobilized from an early endosomal compartment to nascent autophagic membranes, in a TOR- and Atg1-responsive manner. Finally, the well-known TOR substrate S6K (p70 ribosomal protein S6 kinase) has been shown to play a positive role in autophagy, which may serve to limit levels of autophagy under conditions of continuously low TOR activity. Further insight into these TOR-dependent control mechanisms may support development of autophagy-based therapies for a number of pathological conditions.
Fuel cells and their applications (1996)

The book describes a technology dating from the early experiments of the1850s and classical studies of electrochemical systems in the early 1900s predicting that a direct conversion of chemical energy into electricity using fuel cells would be far more efficient at lower temperatures than with combustion processes. The importance of fuel cells for energy saving is explained and evaluated and the extremely low pollution characteristics of dispersed fuel cells are emphasised. Their wide-ranging applications in homes, small factories and power plants, and in some industries for the highly efficient conversion of waste and biomass materials, with the general effect of carbon dioxide reduction in all fossil-fuel-burning processes, are discussed. Their unique uses, for example in high technology spacecrafts and in the development of affordable electric cars, are also detailed.
Monoclonal and Polyclonal Antibodies Reactive with the 1-32 Amino Terminal Sequence of the Alpha Subunit of Human 32K Inhibin (1990)

A monoclonal antibody was made after immunization of mice with the 1-32 amino terminal peptide of the alpha subunit of 32K human ovarian inhibin. The IgG2a mouse antibody reacted 6 times better with bovine 1-32 peptide than it did with 32K bovine inhibin. By contrast sheep polyclonal antibodies made by a similar method had a 29 fold bias in reactivity towards the immunizing peptide. Relative to homologous 1-32 peptide standards, the monoclonal antibody measured apparently higher amounts of immunoreactive material(s) in human (13.5 fold) and bovine (27 fold) follicular fluids than did the polyclonal anti 1-32 peptide antibodies. Immunochemical studies revealed that the epitope recognized by the monoclonal antibody was different from the major epitope recognized by the polyclonal antibodies. The monoclonal antibody reacted much better with human inhibin 1-32 sequences than with bovine (73 fold) or porcine (23 fold). Although the 32K form of human inhibin has not yet been purified, it can be inferred that the monoclonal antibody would be able to detect as little as 2 ng/ml of 32K human inhibin in competitive radioimmunoassays. The antibody must also react with some of the multiple molecular forms of inhibin found in human follicular fluids, and it was shown to function well in the quantitative immunoaffinity extraction of inhibin-like immunoreactivity from follicular fluid. It seems likely that this monoclonal antibody will prove a useful tool for research on human inhibin.
논문 : G통계량을 이용한 시공간 핫스팟 탐지기법 -일본 관동지방의 교통사고 사례연구- (2007)

이 논문에서는 공간자기상관의 통계적 특성을 응용하여 지리현상에서의 시공간 핫스팟을 탐지하는 기법을 제시한다. 국지적 공간자기상관의 지표인 G통계량은 시공간 가중치와 결합하여 시공간 핫스팟 탐지에 활용될 수 있다. 시공간 가중치 체계는 거리조락 및 시간조락의 개념을 반영하여 구성하고, 이를 시공간 버전의 G통계량에 도입함으로써, 각 시점, 각 단위지역의 시공간 자기상관계수를 계산한다. 인접-우세모형에 기초한 핫스팟 탐지 알고리즘은 시점 및 지역별 자기상관계수를 기준으로 시공간 핫스팟을 구획화하여 XY-T(공간-시간)의 입체로 표현한다. 2000년-2005년 일본 관동지방의 교통사고발생 시계열자료에 대한 분석을 통해 이 방법론을 테스트한 결과, 통계적으로 유의미한 수준에서 일정 정도의 자기상관 경향이 발견되었으며, 도쿄도, 군마현, 카나가와현에서 시공간 핫스팟이 탐지되었다. 시공간 핫스팟은 지리현상 발생의 공간적 및 시간적 우세범위를 동시에 표현함으로써 `언제 어디에서`의 연속적 클러스터 정보를 제공한다.
Operation and Performance of Bench Scale Reactors (1957)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOperation and Performance of Bench Scale ReactorsJ. R. Snyder, P. F. Hagerty, and M. C. MolstadCite this: Ind. Eng. Chem. 1957, 49, 4, 689–695Publication Date (Print):April 1, 1957Publication History Published online1 May 2002Published inissue 1 April 1957https://pubs.acs.org/doi/10.1021/ie50568a033https://doi.org/10.1021/ie50568a033research-articleACS PublicationsRequest reuse permissionsArticle Views113Altmetric-Citations22LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options Get e-Alerts
Tumour-educated circulating monocytes are powerful candidate biomarkers for diagnosis and disease follow-up of colorectal cancer (2015)

Our study is the first to demonstrate monocyte plasticity in response to tumour-released soluble factors. The identified distinct signature in tumour-educated monocytes might be used as a candidate biomarker in CRC diagnosis and harbours the potential for disease follow-up and therapeutic monitoring.
Carbon Flux Distribution and Kinetics of Cellulose Fermentation in Steady-State Continuous Cultures of <i>Clostridium cellulolyticum</i> on a Chemically Defined Medium (2001)

The metabolic characteristics of Clostridium cellulolyticum, a mesophilic cellulolytic nonruminal bacterium, were investigated and characterized kinetically for the fermentation of cellulose by using chemostat culture analysis. Since with C. cellulolyticum (i) the ATP/ADP ratio is lower than 1, (ii) the production of lactate at low specific growth rate (mu) is low, and (iii) there is a decrease of the NADH/NAD(+) ratio and q(NADH produced)/ q(NADH used) ratio as the dilution rate (D) increases in carbon-limited conditions, the chemostats used were cellulose-limited continuously fed cultures. Under all conditions, ethanol and acetate were the main end products of catabolism. There was no shift from an acetate-ethanol fermentation to a lactate-ethanol fermentation as previously observed on cellobiose as mu increased (E. Guedon, S. Payot, M. Desvaux, and H. Petitdemange, J. Bacteriol. 181:3262-3269, 1999). The acetate/ethanol ratio was always higher than 1 but decreased with D. On cellulose, glucose 6-phosphate and glucose 1-phosphate are important branch points since the longer the soluble beta-glucan uptake is, the more glucose 1-phosphate will be generated. The proportion of carbon flowing toward phosphoglucomutase remained constant (around 59.0%), while the carbon surplus was dissipated through exopolysaccharide and glycogen synthesis. The percentage of carbon metabolized via pyruvate-ferredoxin oxidoreductase decreased with D. Acetyl coenzyme A was mainly directed toward the acetate formation pathway, which represented a minimum of 27.1% of the carbon substrate. Yet the proportion of carbon directed through biosynthesis (i.e., biomass, extracellular proteins, and free amino acids) and ethanol increased with D, reaching 27.3 and 16.8%, respectively, at 0.083 h(-1). Lactate and extracellular pyruvate remained low, representing up to 1.5 and 0.2%, respectively, of the original carbon uptake. The true growth yield obtained on cellulose was higher, [50.5 g of cells (mol of hexose eq)(-1)] than on cellobiose, a soluble cellodextrin [36.2 g of cells (mol of hexose eq)(-1)]. The rate of cellulose utilization depended on the solid retention time and was first order, with a rate constant of 0.05 h(-1). Compared to cellobiose, substrate hydrolysis by cellulosome when bacteria are grown on cellulose fibers introduces an extra means for regulation of the entering carbon flow. This led to a lower mu, and so metabolism was not as distorted as previously observed with a soluble substrate. From these results, C. cellulolyticum appeared well adapted and even restricted to a cellulolytic lifestyle.
Auger Electron Spectroscopy Element Profiles and Interface with Substrates of Electroless Deposited Ternary Alloys (1996)

Electroless NiMeP alloys (Me = Cu, Sn, Sb) with high phosphorus content (∼11 weight percent) and a low weight percent of the third component (Me) have been plated in acidic baths onto aluminum, iron, and nickel. Scanning Auger electron spectroscopy is applied to study the element profiles and interface with the substrates. Generally the third component follows the profiles of Ni and P, which proves the alloy formation. A surface enrichment in the third element (Me) is observed in all cases. It is very strong when tin is the third component and very weak in the case of antimony, which is more or less uniformly distributed through the thickness. Decrease of surface concentration of phosphorus is noticed when NiSbP is plated. In Cu profiles three different zones exist: a surface enrichment zone, a groove (a zone of reduced concentration), and a plateau (a zone of almost constant concentration). There is no enrichment in the third element at the interface with the substrate for all three alloys and three substrates. At the interface with aluminum prepared for electroless plating with double zincate pretreatment complete dissolution of the zincate layer has been established.
Re-expression of E-cadherin, α-catenin and β-catenin, but not of γ-catenin, in metastatic tissue from breast cancer patients (2000)

Tumour cell invasion and metastasis are the processes which kill most cancer patients. Tumour cells with the greatest invasive and metastatic capacity may be those with the highest number of genetic aberrations. The present study has analysed the expression of several tumour-related proteins in both primary tumours and metastatic lesions from 34 breast cancer patients. Protein expression of p53, bcl-2, p21, cyclin D1, E-cadherin, α-catenin, β-catenin, and γ-catenin was investigated by immunohistochemistry (IHC) using monoclonal antibodies. Metastatic tissue showed a different expression profile from the primary tumour in most patients. The most significant finding was the re-expression of E-cadherin, α-catenin, and β-catenin, and increased down-regulation of γ-catenin, in metastatic lesions. These results demonstrate that tumour cells, when released from the primary site and after regrowth elsewhere, are capable of re-expression of adhesion molecules. γ-catenin may play a different role in metastatic lesions than in primary tumours, since it is selectively down-regulated in tumour tissue at the metastatic site. Copyright © 2000 John Wiley & Sons, Ltd.
Orengedoku-to augmentation in cases showing partial response to yokukan-san treatment: a case report and literature review of the evidence for use of these Kampo herbal formulae (2013)

Together with empirical evidence demonstrating the effectiveness of both yokukansan and orengedoku-to in reducing irritability, impulsivity, and aggression, these three cases suggest that orengedoku-to augmentation can be an effective option in cases that are partially responsive to yokukan-san treatment.
Regulating effect of activated NF-κB on edema induced by traumatic brain injury of rats (2016)

The results show that the activation of NF-κB in astrocytes is a key factor in the process of cerebral edema after TBI of rats.
Structural basis for methylesterase CheB regulation by a phosphorylation-activated domain (1998)

We report the x-ray crystal structure of the methylesterase CheB, a phosphorylation-activated response regulator involved in reversible modification of bacterial chemotaxis receptors. Methylesterase CheB and methyltransferase CheR modulate signaling output of the chemotaxis receptors by controlling the level of receptor methylation. The structure of CheB, which consists of an N-terminal regulatory domain and a C-terminal catalytic domain joined by a linker, was solved by molecular replacement methods using independent search models for the two domains. In unphosphorylated CheB, the N-terminal domain packs against the active site of the C-terminal domain and thus inhibits methylesterase activity by directly restricting access to the active site. We propose that phosphorylation of CheB induces a conformational change in the regulatory domain that disrupts the domain interface, resulting in a repositioning of the domains and allowing access to the active site. Structural similarity between the two companion receptor modification enzymes, CheB and CheR, suggests an evolutionary and/or functional relationship. Specifically, the phosphorylated N-terminal domain of CheB may facilitate interaction with the receptors, similar to the postulated role of the N-terminal domain of CheR. Examination of surfaces in the N-terminal regulatory domain of CheB suggests that despite a common fold throughout the response regulator family, surfaces used for protein-protein interactions differ significantly. Comparison between CheB and other response regulators indicates that analogous surfaces are used for different functions and conversely, similar functions are mediated by different molecular surfaces.