gebhart/patrepeval huggingface dataset:
Therapeutic Protein–Drug Interactions and Implications for Drug Development (2010)

Many intrinsic and extrinsic factors can affect an individual patient's drug exposure and response. The US Food and Drug Administration (FDA) has published a number of guidances that recommend how and when to evaluate these factors during drug development. The most recent FDA draft guidance on drug interactions provides advice for in vitro and in vivo drug interaction studies, including suggestions for study design, dosing strategies and analysis, and interpretation of data for medical product labels. The draft guidance updated the FDA's recommendations on the evaluation of important cytochrome P450 (CYP) enzyme- and transporter-based drug interactions during drug development.
Reduction of Restenosis After Angioplasty in an Atheromatous Rabbit Model by Suicide Gene Therapy (1997)

In vitro, Ad-RSVtk demonstrates selective toxicity toward GCV-treated arterial smooth muscle cells involving apoptosis. In vivo, GCV conditions reduction of neointimal formation after percutaneous delivery of Ad-RSVtk during angioplasty of atheromatous arteries.
Catalytic Peptide of Human Glutaminyl-tRNA Synthetase Is Essential for Its Assembly to the Aminoacyl-tRNA Synthetase Complex (2000)

Human glutaminyl-tRNA synthetase (QRS) is one of several mammalian aminoacyl-tRNA synthetases (ARSs) that form a macromolecular protein complex. To understand the mechanism of QRS targeting to the multi-ARS complex, we analyzed both exogenous and endogenous QRSs by immunoprecipitation after overexpression of various Myc-tagged QRS mutants in human embryonic kidney 293 cells. Whereas a deletion mutant containing only the catalytic domain (QRS-C) was targeted to the multi-ARS complex, a mutant QRS containing only the N-terminal appended domain (QRS-N) was not. Deletion mapping showed that the ATP-binding Rossman fold was necessary for targeting of QRS to the multi-ARS complex. Furthermore, exogenous Myc-tagged QRS-C was co-immunoprecipitated with endogenous QRS. Since glutaminylation of tRNA was dramatically increased in cells transfected with the full-length QRS, but not with either QRS-C or QRS-N, both the QRS catalytic domain and the N-terminal appended domain were required for full aminoacylation activity. When QRS-C was overexpressed, arginyl-tRNA synthetase and p43 were released from the multi-ARS complex along with endogenous QRS, suggesting that the N-terminal appendix of QRS is required to keep arginyl-tRNA synthetase and p43 within the complex. Thus, the eukaryote-specific N-terminal appendix of QRS appears to stabilize the association of other components in the multi-ARS complex, whereas the C-terminal catalytic domain is necessary for QRS association with the multi-ARS complex.
Polynucleotide kinase exchange reaction: quantitave assay for restriction endonuclease-generated 5'-phosphoroyl termini in DNA. (1977)

Mimi Zeiger is a writer, critic, curator and editor. She’s written for a variety of publications including The New York Times, Dwell, Domus, and The Architectural Review and is the founder of Loud Paper, a zine and digital publication that sought to increase the output of architectural discourse. She was also the co-curator for the US Pavilion at the 2018 Venice Architecture Biennale, which had the theme “Dimensions of Citizenship.” In this episode, Mimi and I talk about how she started writing after beginning a career as an architect, the role of the critic, and why we need architecture and ...
Angiographic and clinical predictors of acute closure after native vessel coronary angioplasty. (1988)

To determine predictors of acute coronary closure after PTCA performed with steerable catheter systems, we compared 140 procedures complicated by acute closure and 311 representative successful attempts from 4,772 procedures performed between April 1982 and March 1986. Sixteen clinical, 35 angiographic, and seven procedural variables were analyzed. Multivariate analysis found seven independent preprocedural factors related to closure: stenosis length of 2 or more luminal diameters, female gender, stenosis at a bend point of 45 degrees or more, stenosis at a branch point, stenosis-associated thrombus (filling defect or staining), other stenoses in the same vessel, and multivessel disease. In addition, four procedural factors were found to be associated with closure by univariate analysis: post-PTCA percent stenosis (p less than .001), intimal tear or dissection (p less than .001), use of prolonged heparin infusion (p less than .001), and post-PTCA gradient of 20 mm Hg or more (p = .004). Multivariate analysis of both preprocedural and procedural variables found six factors independently related to closure: post-PTCA percent stenosis, dissection, prolonged post-PTCA use of heparin, branch point location, fixed bend point location, and other stenoses in the vessel dilated. The risk of coronary closure after PTCA has many determinants. While an estimation of risk can be made before performing PTCA, the most powerful predictors of closure can only be assessed during the procedure itself.
Targeting IL-23 in autoimmunity. (2005)

Dysregulated cell-mediated immune responses may lead to chronic inflammation and autoimmune disorders. The recent discovery of the dimeric interleukin (IL)-12-related cytokine IL-23 now adds to our understanding of the fine-tuning of cellular immunity. The critical implication of the role that IL-12p40 plays in autoimmune inflammation has long been misinterpreted and only recently have studies revealed that it is IL-23, and not IL-12, that is the decisive factor in this immune deviation. Therefore, targeting of IL-23 or the IL-23 receptor is a promising therapeutic approach for autoimmune diseases. This review summarizes recent findings regarding IL-23-mediated autoreactive inflammatory responses, and introduces possible therapeutic interventions that are aimed at mitigating autoimmune inflammation.
Tunable wavelength filters using λ/4-shifted waveguide grating resonators (1988)

We report on wide tuning range 1.5 μm wavelength filters using λ/4-shifted waveguide grating resonators. A tuning range of a transmission resonance wavelength as wide as 42 Å by carrier injection and two-channel wavelength signal switching was achieved.
Centella asiatica in cosmetology (2013)

Centella asiatica known as Gotu Kola is a medicinal plant that has been used in folk medicine for hundreds of years as well as in scientifically oriented medicine. The active compounds include pentacyclic triterpenes, mainly asiaticoside, madecassoside, asiatic and madecassic acids. Centella asiatica is effective in improving treatment of small wounds, hypertrophic wounds as well as burns, psoriasis and scleroderma. The mechanism of action involves promoting fibroblast proliferation and increasing the synthesis of collagen and intracellular fibronectin content and also improvement of the tensile strength of newly formed skin as well as inhibiting the inflammatory phase of hypertrophic scars and keloids. Research results indicate that it can be used in the treatment of photoaging skin, cellulite and striae.
ChamNet: Towards Efficient Network Design through Platform-Aware Model Adaptation (2018)

This paper proposes an efficient neural network (NN) architecture design methodology called Chameleon that honors given resource constraints. Instead of developing new building blocks or using computationally-intensive reinforcement learning algorithms, our approach leverages existing efficient network building blocks and focuses on exploiting hardware traits and adapting computation resources to fit target latency and/or energy constraints. We formulate platform-aware NN architecture search in an optimization framework and propose a novel algorithm to search for optimal architectures aided by efficient accuracy and resource (latency and/or energy) predictors. At the core of our algorithm lies an accuracy predictor built atop Gaussian Process with Bayesian optimization for iterative sampling. With a one-time building cost for the predictors, our algorithm produces state-of-the-art model architectures on different platforms under given constraints in just minutes. Our results show that adapting computation resources to building blocks is critical to model performance. Without the addition of any bells and whistles, our models achieve significant accuracy improvements against state-of-the-art hand-crafted and automatically designed architectures. We achieve 73.8% and 75.3% top-1 accuracy on ImageNet at 20ms latency on a mobile CPU and DSP. At reduced latency, our models achieve up to 8.5% (4.8%) and 6.6% (9.3%) absolute top-1 accuracy improvements compared to MobileNetV2 and MnasNet, respectively, on a mobile CPU (DSP), and 2.7% (4.6%) and 5.6% (2.6%) accuracy gains over ResNet-101 and ResNet-152, respectively, on an Nvidia GPU (Intel CPU).
Host and Vector-dependent Effects on the Risk of Germline Transmission of AAV Vectors (2009)

The assessment of the risk of germline transmission of vector-coded sequences is critical for clinical translation of gene transfer strategies. We used rabbit models to analyze the risk of germline transmission of adeno-associated viral (AAV) vectors. Intravenous injection of AAV-2 or AAV-8 resulted in liver-mediated, long-term expression of therapeutic levels of human factor IX (hFIX) in a dose-dependent manner. In high-dose cohorts, AAV-8 resulted in twofold higher levels of circulating hFIX and of vector DNA in liver compared to AAV-2. Vector sequences were found in the semen of all rabbits. The kinetics of vector clearance from semen was dose- and time-dependent but serotype-independent. No late recurrence of AAV-8 sequences was found in the semen over several consecutive cycles of spermatogenesis. In a novel rabbit model, AAV-2 or AAV-8 sequences were detected in the semen of vasectomized animals that lack germ cells. Therefore, structures of the genitourinary (GU) tract, as well as the testis, contribute significantly to vector shedding in the semen. Collectively, data from these two models suggest that the risk of inadvertent germline transmission in males by AAV-8 vectors is low, similar to that of AAV-2, and that AAV dissemination to the semen is in part modulated by host-dependent factors.
Characterization of microarray gene expression profiles of early stage thyroid tumours. (2008)

The role of overlapping genes in histologically different tumours has not been clarified, but might represent early or pivotal steps of carcinogenesis. All investigated histiotypes of tumours contained significantly modulated genes acting on the NF-kappaB regulatory pathway. Our findings suggest that modulation of NF-kappaB signalling plays a crucial role in early thyroid carcinogenesis.
Effect of Nondopaminergic Drugs on L-DOPA-Induced Dyskinesias in MPTP-Treated Monkeys (1993)

A group of four monkeys was rendered parkinsonian with the toxin MPTP. They were then treated chronically with L-DOPA/benserazide 50/12.5 mg/kg given orally daily for 2 months. This dose produced a striking antiparkinsonian effect, but all animals manifested dyskinesia. A series of agents acting primarily on neurotransmitters other than dopamine were then tested in combination with L-DOPA to see if the dyskinetic movements would be modified. Several drugs, including clonidine, physostigmine, methysergide, 5-MDOT, propranolol, and MK-801, markedly reduced the dyskinetic movements but at the cost of a return of parkinsonian symptomatology. However, yohimbine and meperidine reduced predominantly the dyskinetic movements. Baclofen was also useful in one monkey against a more dystonic form of dyskinesia. Atropine converted the dystonic movements into chorea.
Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer (2005)

Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting effects in mouse skin. In this study, employing human prostate cancer cells, we evaluated the antiproliferative and proapoptotic properties of PFE. PFE (10-100 μg/ml; 48 h) treatment of highly aggressive human prostate cancer PC3 cells resulted in a dose-dependent inhibition of cell growth/cell viability and induction of apoptosis. Immunoblot analysis revealed that PFE treatment of PC3 cells resulted in ( i ) induction of Bax and Bak (proapoptotic); ( ii ) down-regulation of Bcl-X L and Bcl-2 (antiapoptotic); ( iii ) induction of WAF1/p21 and KIP1/p27; ( iv ) a decrease in cyclins D1, D2, and E; and ( v ) a decrease in cyclin-dependent kinase (cdk) 2, cdk4, and cdk6 expression. These data establish the involvement of the cyclin kinase inhibitor-cyclin-cdk network during the antiproliferative effects of PFE. Oral administration of PFE (0.1% and 0.2%, wt/vol) to athymic nude mice implanted with androgen-sensitive CWR22Rν1 cells resulted in a significant inhibition in tumor growth concomitant with a significant decrease in serum prostate-specific antigen levels. We suggest that pomegranate juice may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against prostate cancer in humans.
Metabolism of fluorescein after intravenous administration. (1985)

The measurement of plasma unbound (free) fluorescein is important in the study of blood-ocular barrier kinetics. The authors became concerned about the quantitative significance of the presumed glucuronide metabolite of fluorescein to the measurement of plasma fluorescence in diabetic and normal subjects. Fluorescein was given intravenously (14 mg/kg) to seven normal subjects and eight diabetic subjects. Plasma samples taken during 60 min were subjected to microfiltration, from which aliquots of ultrafiltrate were incubated with beta-glucuronidase. Samples were subjected to high-performance liquid chromatography, and fluorescence activity was measured in the eluent. All subjects showed an additional fluorescence peak to that of fluorescein in plasma and ultrafiltrate 5 min after fluorescein administration and increased thereafter. This additional peak was abolished by incubation of ultrafiltrate with beta-glucuronidase and resulted in a marked increase in fluorescence due to the liberation of fluorescein from its presumed glucuronide. There were no pharmacokinetic differences between normal and diabetic subjects in plasma-free fluorescein and fluorescein glucuronide pharmacokinetics or in their respective binding to plasma proteins. The glucuronide had only 4.5% of the fluorescence of fluorescein, but because more of the glucuronide was unbound (32%) compared with fluorescein (10%) and its concentration increased while that of fluorescein decreased, it constituted an increasing proportion of the fluorescence in the ultrafiltrate. At 60 min, 80% of the fluorescein was present as glucuronide and contributed 20% of the total fluorescence in the ultrafiltrate. Fluorescein-glucuronide is a potential source of variability in studies on blood-ocular barrier kinetics.
Chiral recognition in clefts and cyclophane cavities shaped by the 1,1'-binaphthyl major groove (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral recognition in clefts and cyclophane cavities shaped by the 1,1'-binaphthyl major groovePeter P. Castro, Taxiarchis M. Georgiadis, and Francois DiederichCite this: J. Org. Chem. 1989, 54, 25, 5835–5838Publication Date (Print):December 1, 1989Publication History Published online1 May 2002Published inissue 1 December 1989https://doi.org/10.1021/jo00286a003RIGHTS & PERMISSIONSArticle Views358Altmetric-Citations36LEARN 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 InReddit PDF (506 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Sensitivity calibration with a uniform magnetization image to improve arterial spin labeling perfusion quantification (2011)

Quantification of perfusion with arterial spin labeling MRI requires a calibration of the imaging sensitivity to water throughout the imaged volume. Since this sensitivity is affected by coil loading and other interactions between the subject and the scanner, the sensitivity must be calibrated in the subject at the time of scan. Conventional arterial spin labeling perfusion quantification assumes a uniform proton density and acquires a proton density reference image to serve as the calibration. This assumption, in the form of an assumed constant brain-blood partition coefficient, incorrectly adds inverse proton density weighting to the perfusion image. Here, a sensitivity calibration is proposed by generating a uniform magnetization image whose intensity is highly independent of brain tissue type. It is shown that such a uniform magnetization image can be achieved, and brain tissue perfusion values quantified with the sensitivity calibration agree with those quantified with a proton density image when segmentation of brain tissues is performed and appropriate partition coefficients are assumed. Quantification of brain tissue water density is also demonstrated using this sensitivity calibration. This approach can improve and simplify quantification of arterial spin labeling perfusion and may have broader applications to measurement of edema and sensitivity calibration for parallel imaging.
A Study on Knocking Characteristics of a 300 kW Class CNG Engine for CHP (2008)

Among the various prime movers for combined heat and power (CHP) system, the CNG engine is the most commonly used power generation equipment of which power is less than 1MW. The 300 kW class CNG engine for CHP can meet stringent emission regulations with the adoption of stoichiometric air-fuel ratio control and three way catalyst. As the thermal efficiency of the stoichiometric ratio engine is lower than that of lean burn engine, it is necessary to operate the stoichiometric engine at its minimum spark advance for the best torque (MBT). However, knock control should be introduced for the engine under high intake air temperature conditions because MBT operating conditions are generally very close to those of knock occurrence. In this study, engine performances and knocking characteristics were experimentally investigated for the CNG engine that needs to be operated at higher intake air temperature conditions than normal conditions.
Letters to the Editor (2000)

Department of Pediatric Orthopedics No. 2 Hospital of CMU Shang Yang, Liao Ning People's Republic of China
Extracellular Matrix Scaffold for Cardiac Repair (2005)

Appearance of a fibrocellular tissue that included contractile cells accompanied biodegradation of UBM when implanted as an LV-free wall infarction patch. UBM appears superior to synthetic material for cardiac patching and trends toward myocardial replacement at 3 months.
Web-a-where (2004)

We describe Web-a-Where, a system for associating geography with Web pages. Web-a-Where locates mentions of places and determines the place each name refers to. In addition, it assigns to each page a geographic focus --- a locality that the page discusses as a whole. The tagging process is simple and fast, aimed to be applied to large collections of Web pages and to facilitate a variety of location-based applications and data analyses.Geotagging involves arbitrating two types of ambiguities: geo/non-geo and geo/geo. A geo/non-geo ambiguity occurs when a place name also has a non-geographic meaning, such as a person name (e.g., Berlin) or a common word (Turkey). Geo/geo ambiguity arises when distinct places have the same name, as in London, England vs. London, Ontario.An implementation of the tagger within the framework of the WebFountain data mining system is described, and evaluated on several corpora of real Web pages. Precision of up to 82% on individual geotags is achieved. We also evaluate the relative contribution of various heuristics the tagger employs, and evaluate the focus-finding algorithm using a corpus pretagged with localities, showing that as many as 91% of the foci reported are correct up to the country level.
A 20-Year Population-Based Study of Postdiarrheal Hemolytic Uremic Syndrome in Utah (1994)

HUS has been an important clinical and public health problem in Utah for 20 years. The consistency of the clinical and epidemiologic features over 2 decades suggests that a common etiologic agent has accounted for most cases of HUS in this region since 1971.
Carcinoma-associated expression of core 2 beta-1,6-N-acetylglucosaminyltransferase gene in human colorectal cancer: role of O-glycans in tumor progression. (1997)

Recently, it was demonstrated that an increased level of NeuNAc alpha2-3Gal beta1-4(Fuc alpha1-3)GlcNAc beta-R (sialyl Le(x)) and NeuNAc alpha2-3Gal beta1-3(Fuc alpha1-4)GlcNAc beta-R (sialyl Le(a)) expression on the surface of colorectal cancer cells is positively correlated with progression of the disease. It has not been determined, however, which type of glycans, N- or O-glycans, is more closely associated with progression when cancer cells express those oligosaccharides. To address this problem, we have examined expression of sialyl Le(a) and sialyl Le(x), those oligosaccharides in O-glycans, and core 2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT) transcripts in colorectal cancer specimens from 46 patients and compared those results with clinicopathological variables. C2GnT is a glycosyltransferase that is responsible for the core 2 branch, which is critical for biosynthesis of sialyl Le(a) and sialyl Le(x) in O-glycans. Sialyl Le(a) and sialyl Le(x) were determined by immunohistochemistry, and C2GnT transcripts were detected by reverse transcription-PCR. Sialyl Le(a) or sialyl Le(x) in O-glycans was assessed by combining immunohistochemistry for sialyl Le(a) or sialyl Le(x) with reverse transcription-PCR for C2GnT. Sialyl Le(a), detected on cancer cells in 74% of patients, was well correlated with lymph node metastasis, whereas sialyl Le(a) and sialyl Le(x) in O-glycans, which were specifically detected in cancer tissues of 50 and 61% of patients, respectively, were closely associated with lymphatic and venous invasion. In addition, C2GnT, which was specifically detected in cancer tissues of 63% of patients, was closely correlated with the vessel invasion, as well as depth of tumor invasion. These results strongly suggest that sialyl Le(a) and sialyl Le(x) in O-glycans and C2GnT, expressed in cancer cells, may play important roles in tumor progression through vessel or direct invasion.