gebhart/patrepeval huggingface dataset:
Discovery, Modeling, and Human Pharmacokinetics of<i>N</i>-(2-Acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a Second Generation, ET<sub>A</sub>Selective, and Orally Bioavailable Endothelin Antagonist (2004)

Sitaxsentan (1) (Wu et al. J. Med. Chem. 1997, 40, 1690) is our first endothelin antagonist being evaluated in clinical trials. It has demonstrated biological effects in an acute hemodynamic study in CHF (Givertz et al. Circulation 2000, 101, 2922), an open-label 20-patient pulmonary hypertension trial (Barst et al. Chest 2002, 121, 1860-1868), and a 31-patient trial in essential hypertension (Calhoun et al. AHA Scientific Sessions 2000). In a phase 2b/3 pulmonary arterial hypertension trial, once a day treatment of 100 mg of sitaxsentan statistically significantly improved 6-min walk distance and NYHA class at 12 weeks (Barst et al. Am. J. Respir. Crit. Care Med. 2004, 169, 441). We have since reported on our efforts in generating follow-up compounds (Wu et al. J. Med. Chem. 1999, 42, 4485) and recently communicated that an ortho acyl group on the anilino ring enhanced oral absorption in this category of compounds (Wu et al. J. Med. Chem. 2001, 44, 1211). Here we report an expansion of this work by substituting a variety of electron-withdrawing groups at the ortho position and evaluating their effects on oral bioavailability as well as structure-activity relationships. As a result, TBC3711 (7z) was identified as our second endothelin antagonist to enter the clinic due to its good oral bioavailability (approximately 100%) in rats, high potency (ET(A) IC(50) = 0.08 nM), and optimal ET(A)/ET(B) selectivity (441 000-fold). Compound 7z has completed phase-I clinical development and was well tolerated with desirable pharmacokinetics in humans (t(1/2) = 6-7 h, oral availability > 80%).
Drainhole drilling. Part. 1. Variables in kickoff remain first consideration during drainhole drilling (1981)

Drainholes are approximately horizontal holes drilled from an approximate vertical well bore. A drainhole is composed of 2 parts, a curved section in which the bore is turned from vertical to horizontal and a straight or stabilized section. The curved section has sharp radii as small as 12 ft and seldom larger than 40 ft. The stabilized section is not really straight, but usually a curved section of much larger radius. Typical radii for the stabilized section are 300 to 500 ft. Drainholes were initially field tested as a productivity enhancement technique in the early 1950's. They did not prove to be economic, especially compared to the low cost fracture treatments of that time. Difficulties also were noted in taking off from the whipstock and controlling the direction of the drainhole. A few drainholes were reported later in Italy and some were used in oil shale in situ field projects. Interest in drainhole drilling has revived with the rising cost of oil and gas. It is the more sophisticated of exploitive possibilities offered by this technique that are now of interest.
Partially-Activated Conjugate Beamforming for LoS Massive MIMO Communications (2018)

A partially activated conjugate beamforming (PACB) is proposed for massive multiple-input multiple-output communications, where the line-of-sight (LoS) channel is dominant. Unlike the conventional conjugate beamforming which activates all the antenna elements to radiate the signals, our PACB activates only a fraction of the antennas by exploiting the spatial structure of LoS channel, and it can mitigate the inter-user interference more effectively, leading to dramatically enhanced downlink spectral efficiency. A low-complexity search algorithm is also introduced to calculate the optimal number of activated antennas. Theoretical analysis and simulation results both confirm that our PACB offers significantly higher downlink spectral efficiency compared to its conventional beamforming counterpart.
Treatment of heart failure in infants and children. (2001)

In its simplest and most succinct definition, heart failure can be defined as an inability of the heart to meet the metabolic demands of the body. Despite the diverse etiologies of heart failure in the pediatric population, the presentation of heart failure represents a common constellation of symptoms, signs, and physical findings. In infants, an inability to maintain growth either secondary to decreased nutritional intake or an increased catabolic state is a hallmark of heart failure. Infants exhibit increased sympathetic tone with excessive diaphoresis and increased heart rate. Physical findings in the infants with congestive heart failure (CHF) include increased work of breathing, tachypnea and hepatomegaly. In older children, in contrast, new onset heart failure may be less overtly symptomatic. Malaise, decrease in the level of daily activity, and weight loss may be present. Symptoms of abdominal pain and nausea and anorexia can be present and sometimes divert attention from the real etiology. Physical findings include rales and peripheral edema. If there is hepatomegaly, there will likely be hepatic tenderness as well. A gallop rhythm and tachycardia are commonly present. The long-term treatment of CHF in children includes digoxin, diuretics and afterload reduction with angiotensin-converting enzyme (ACE) inhibitors. Digoxin decreases sympathetic tone and improves growth in infants. Diuretics should be used to relieve symptoms but may not be necessary in all children. ACE inhibitors are increasingly valuable in maintaining cardiac function long term. New uses of medications include the addition of spironalactone (Aldactone, G. D. Searle & Co., Chicago, IL) which, in adults, has been shown to significantly decrease both the death rate from CHF and the need for hospitalization. Beta-Blockers have been used in children in limited studies and may have a role in the treatment of patients with idiopathic dilated cardiomyopathy. Surgical treatment, such as partial vectriculectomy, has shown short-term benefit and has been used sparingly in infants.
Xanthine Oxidase Mediates Axonal and Myelin Loss in a Murine Model of Multiple Sclerosis (2013)

These results highlight the implication of XO in EAE pathogenesis and suggest XO as a target for MS treatment and febuxostat as a promising therapeutic option for MS neuropathology.
THE EFFECT OF WHOLE SUNFLOWER SEEDS ON THE FLOW OF FAT AND FATTY ACIDS THROUGH THE GASTROINTESTINAL TRACT OF CANNULATED HOLSTEIN STEERS (1987)

Four cannulated (rumen, abomasum and ileum) Holstein steers were randomly allotted to four experimental diets in a 4 × 4 Latin square design. Diets contained (1) 4% sunflower oil (SFO); (2) 10% whole sunflower seeds (WSS); (3) 20% WSS and (4) 10% canola meal (LFCM). Dysprosium was used to calculate the flow of the particulate digesta through the gastrointestinal (GI) tract. The ratio of rumen acetate to propionate was increased (P < 0.05) when the LFCM diet was fed compared to when the three oil- or seed-containing diets were fed; there were no differences (P < 0.05) among the oil- or seed-containing diets. Apparent output of fat from the rumen compared to dietary intake was increased (P < 0.05) for all diets except SFO. Differences in fatty acid flow among the four diets diminished (P < 0.05) as the fat flowed through the GI tract. There was a decreased (P < 0.05) output of linoleic acid and an increased (P < 0.05) output of stearic and palmitic acids in the rumen compared to the dietary intake. The three oil diets had a higher (P < 0.05) flow of octadecanoic acids through the GI tract than the LFCM diet, and only the flow of stearic acid through the rumen differed (P < 0.05) among the three oil diets. Apparent digestibilities of dry matter (DM), crude protein (CP), and energy were not different (P < 0.05) among the four diets. Fiber digestibility was unaffected by the increasing fat levels. Fat digestion coefficients increased with increasing dietary intake of fat, and calculated true digestibility of sunflower oil was 83.4%. Key words: Sunflower seeds (whole), fatty acid flow, gastrointestinal tract (lower)
<i>ERP57</i> secretion is important for extracellular matrix accumulation and renal fibrosis progression and is an earlier sign of disease onset (2013)

Renal fibrosis is characterized by excessive accumulation of extracellular matrix (ECM), which compromises organ function by replacing normal organ tissue. The molecular mechanisms leading to renal fibrosis are not fully understood. Here we demonstrated that TGFβ1, AGT or PDGF stimulation of renal cells resulted in endoplasmic reticulum (ER) stress followed by activation of the protective unfolded protein response pathway and a high secretory level of protein disulfide isomerase ERP57 (also known as PDIA3). The TGFβ1-induced impairment of ER function could be reversed by treatment with BMP7, suggesting a specific involvement in renal fibrosis. A clear correlation between the degree of fibrosis, ER stress and the level of ERP57 could be seen in fibrosis animal models and in biopsies of renal fibrosis patients. Protein interaction studies revealed that secreted ERP57 exhibits a strong interaction with ECM proteins. Knockdown of ERP57 or antibody-targeted inhibition of the secreted form significantly impaired the secretion and accumulation of ECM. Moreover, ERP57 was excreted in the early stages of chronic kidney disease, and its level in urine correlated with the degree of renal fibrosis, suggesting that the secretion of ERP57 represents one of the first signs of renal fibrosis onset and progression.
Cold acclimation or grapeseed oil feeding affects phospholipid composition and mitochondrial function in duckling skeletal muscle (2000)

The phospholipid fatty acid (FA) composition and functional properties of skeletal muscle and liver mitochondria were examined in cold-acclimated (CA, 4 degrees C) ducklings. Phospholipid FA of isolated muscle mitochondria from CA birds were longer and more unsaturated than those from thermoneutral (TN, 25 degrees C) reared ducklings. The rise in long-chain and polyunsaturated FA (PUFA, mainly 20:4n-6) was associated with a higher State 4 respiration rate and a lower respiratory control ratio (RCR). Hepatic mitochondria, by contrast, were much less affected by cold acclimation. The cold-induced changes in phospholipid FA profile and functional properties of muscle mitochondria were reproduced by giving TN ducklings a diet enriched in grapeseed oil (GO, rich in n-6 FA), suggesting a causal relationship between the membrane structure and mitochondrial functional parameters. However, hepatic mitochondria from ducklings fed the GO diet also showed an enrichment in long-chain PUFA but opposite changes in their biochemical characteristics (lower State 4, higher RCR). It is suggested that the differential modulation of mitochondrial functional properties by membrane lipid composition between skeletal muscle and liver may depend on muscle-specific factors possibly interacting with long-chain PUFA and affecting the proton leakiness of mitochondrial membranes.
Adipose tissue dysfunction in obesity, diabetes, and vascular diseases (2008)

The classical perception of adipose tissue as a storage place of fatty acids has been replaced over the last years by the notion that adipose tissue has a central role in lipid and glucose metabolism and produces a large number of hormones and cytokines, e.g. tumour necrosis factor-alpha, interleukin-6, adiponectin, leptin, and plasminogen activator inhibitor-1. The increased prevalence of excessive visceral obesity and obesity-related cardiovascular risk factors is closely associated with the rising incidence of cardiovascular diseases and type 2 diabetes mellitus. This clustering of vascular risk factors in (visceral) obesity is often referred to as metabolic syndrome. The close relationship between an increased quantity of visceral fat, metabolic disturbances, including low-grade inflammation, and cardiovascular diseases and the unique anatomical relation to the hepatic portal circulation has led to an intense endeavour to unravel the specific endocrine functions of this visceral fat depot. The objective of this paper is to describe adipose tissue dysfunction, delineate the relation between adipose tissue dysfunction and obesity and to describe how adipose tissue dysfunction is involved in the development of diabetes mellitus type 2 and atherosclerotic vascular diseases. First, normal physiology of adipocytes and adipose tissue will be described.
Reasoning about Uncertainty in Prognosis: A Confidence Prediction Neural Network Approach (2005)

Uncertainty representation and management is the Achilles heel of fault prognosis in condition based management systems. Long-term prediction of the time to failure of critical military and industrial systems entails large-grain uncertainty that must be represented effectively and managed efficiently, i.e. as more data becomes available, means must be devised to narrow or "shrink" the uncertainty bounds. Prediction accuracy and precision are typical performance metrics employed to access the performance of prognostic algorithms. That is, we would like the predicted time to failure to be as close as possible to the real one. Also, the bounds or limits of uncertainty must be as "narrow" as possible. This paper introduces a novel confidence prediction neural network construct with a confidence distribution node based on a Parzen estimate to represent uncertainty and a learning algorithm implemented as a lazy or Q-learning routine that improves online prognostics estimates. The approach is illustrated with test and simulation results obtained from a faulty helicopter planetary gear plate.
Telomere Length as a Tool to Monitor Satellite Cell Amplification for Cell-Mediated Gene Therapy (1996)

Cell-mediated gene therapy requires an in vitro amplification of modified cells prior to their injection into target tissue. Since the proliferative capacity of normal human cells is limited, we have tested a method to follow in vitro the proliferative potential of human satellite cells. Our results show that telomere length can be used to predict the proliferative potential of human satellite cells. In this short communication, the telomere shortening and the limited replicative potential are discussed in the context of the possible use of human satellite cells for gene transfer and why cell-mediated gene therapy has been less successful in humans than in mice.
Assessment of microscopic hematuria in adults. (2006)

Microscopic hematuria, a common finding on routine urinalysis of adults, is clinically significant when three to five red blood cells per high-power field are visible. Etiologies of microscopic hematuria range from incidental causes to life-threatening urinary tract neoplasm. The lack of evidence-based imaging guidelines can complicate the family physician's decision about the best way to proceed. Patients with proteinuria, red cell casts, and elevated serum creatinine levels should be referred promptly to a nephrology subspecialist. Microscopic hematuria with signs of urinary tract infection should resolve with appropriate treatment of the underlying infection. Patients with asymptomatic microscopic hematuria or with hematuria persisting after treatment of urinary tract infection also need to be evaluated. Because upper and lower urinary tract pathologies often coexist, patients should be evaluated using cytology plus intravenous urography, computed tomography, or ultrasonography. When urine cytology results are abnormal, cystoscopy should be performed to complete the investigation.
A red emitting two-photon fluorescent probe for dynamic imaging of redox balance meditated by a superoxide anion and GSH in living cells and tissues (2016)

Cellular self-regulation of reactive oxygen species (ROS) stress via antioxidant repair plays an important role in maintaining the redox balance. The redox balance between reducing and oxidizing species within cells is significant in the regulation of a signal pathway and is achieved by a series of elaborate mechanisms. In this work, we employed our previously reported D-π-A-structured naphthalene-BODIPY TBET platform to design an efficient two-photon fluorescent probe for dynamic monitoring of superoxide anion oxidative stress and the GSH reducing repair process. The probe displayed high energy transfer efficiency (91.4%), large pseudo-Stokes shifts upon one-photon excitation, and red fluorescence emission (λ<sub>em</sub> = 596 nm), which is highly desirable for bioimaging applications. The probe exhibits reversibility, rapid response, good photostability, high selectivity and sensitivity for the superoxide anion and GSH. More importantly, the probe was successfully applied for visualizing the redox changes in living cells and tissues.
[Action of doxorubicin and a doxorubicin-heparin complex on the growth and metastasis of experimental tumors and the hemostatic system indices]. (1988)

The electrophoretic and spectral analyses have been used to show the possibility to form a complex consisting of doxorubicin and adriamycin with heparin, the molar ratio being 6:1 and pH 4.8-7.4. Doxorubicin and adriamycin had procoagulant properties but the doxorubicin-heparin complex showed an anticoagulant activity. In experiments on rats with the Pliss lymphosarcoma and sarcoma 45 the doxorubicin-heparin complex depressed more efficiently the tumour growth and metastasis spreading. The combination of doxorubicin and the doxorubicin heparin complex with the trypsin-heparin complex which imitate the hyperfunction of anticoagulative system markedly increased the antitumour effects.
Hierarchical pattern classification for high performance text-independent speaker verification systems (2002)

A new algorithm, the hierarchical speaker verification algorithm, is introduced. This algorithm employs a set of unique mapping functions determined from an enrolment utterance that characterize the target voice as a multidimensional martingale random walk process. For sufficiently long verification utterances, the central limit theorem insures that the accumulated scores for the target speaker will be distributed normally about the origin. Impostor speakers, which violate the martingale property, are distributed arbitrarily and widely scattered in the verification space. Excerpts of verification performance experiments are given and extensions to the algorithm for handling noisy channels and speaker template aging are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Solutions to Resist Pattern Collapse for 45nm Lithography (2006)

Two approaches to prevent pattern collapse of 45 nm photoresist features were explored to create a process which minimizes the forces attributed to collapse while increasing adhesion forces. Two different bottom anti-reflective coatings (BARC), a first and second reflectance minimum were examined in conjunction with the experimental approaches. An initial characterization of pattern collapse was performed to act as a control to gauge the effectiveness of the experimental approaches using an exposure matrix. The first approach implemented a surfactant added to the de-ionized (DI) water rinse after develop to decrease the capillary forces between the features. The second approach created more topography to the surface of the BARC in order to provide more surface area for the resolved feature to adhere to.
Patterning of Tantalum Polycide Films (1984)

Gate level interconnect composed of a layer of doped polysilicon covered by a refractory metal silicide (polycide structure) is becoming an important feature of some integrated circuit technologies. These composite structures retain the relatively well characterized polysilicon/SiO/sup 2/ interface while permitting a lower resistivity than possible with polysilicon alone. Dry etching chemistries used for patterning polysilicon are not generally compatible with these composite materials, often producing an undesirable etched line profile or other complications. For example, a fluorine based plasma will typically etch the polysilicon out from under the silicide resulting in an overhang that will reduce step coverage by subsequent depositions. It has been recently shown that by adding C1/sup 2/ to an SF/sup 6/ plasma, a continuous profile can be formed on Ta polycide lines. In this paper the authors discuss the etching behavior of TaSi/sup 2//polysilicon films in a BC1/sup 3//C1/sup 2/ based reactive ion etching process. Control of the etched line profile by variation of the process parameters is emphasized.
Dynamic Surface Properties of Amino-Terminated Self-Assembled Monolayers Incorporating Reversible CO<sub>2</sub> Chemistry (2011)

An innovative approach to creating a dynamically controllable smart surface is proposed, incorporating the reversible reaction of CO2 with free primary and secondary amines of amino-terminated self-assembled monolayers (SAMs). Solutions of N-(2-aminoethyl)(3-aminopropyl)methyldimethoxysilane (AEAPMDS), N-(6-aminohexyl)-3-aminopropyltrimethoxysilane (AHAPTS), and trimethoxysilylpropyl(polyethleneimine) (PEI-silane) were exposed to CO2, producing the respective carbamate species. The reacted CO2 was readily released by application of moderate heating and reduced pressure. Thermogravametric analysis (TGA) showed a weight loss percentage corresponding to 1 mol of CO2 per 1 mol of diamine at roughly 50 °C, and attenuated total reflectance Fourier transform infrared (ATR FTIR) spectroscopy confirmed the formation of the carbamate species. Well-ordered amino-terminal SAMs of AEAPMDS, AHAPTS, and PEI-silane were prepared on silicon substrates from toluene solutions and were then exposed to CO2. The subsequent changes in the surface structure and wettability were characterized by variable-angle ellipsometry, atomic force microscopy (AFM), and static contact-angle goniometry. The SAMs showed a reversible change in layer thickness coupled with an increase in hydrophilicity upon CO2 exposure.
Calcium Sparks (2008)

The calcium ion (Ca(2+)) is the simplest and most versatile intracellular messenger known. The discovery of Ca(2+) sparks and a related family of elementary Ca(2+) signaling events has revealed fundamental principles of the Ca(2+) signaling system. A newly appreciated "digital" subsystem consisting of brief, high Ca(2+) concentration over short distances (nanometers to microns) comingles with an "analog" global Ca(2+) signaling subsystem. Over the past 15 years, much has been learned about the theoretical and practical aspects of spark formation and detection. The quest for the spark mechanisms [the activation, coordination, and termination of Ca(2+) release units (CRUs)] has met unexpected challenges, however, and raised vexing questions about CRU operation in situ. Ample evidence shows that Ca(2+) sparks catalyze many high-threshold Ca(2+) processes involved in cardiac and skeletal muscle excitation-contraction coupling, vascular tone regulation, membrane excitability, and neuronal secretion. Investigation of Ca(2+) sparks in diseases has also begun to provide novel insights into hypertension, cardiac arrhythmias, heart failure, and muscular dystrophy. An emerging view is that spatially and temporally patterned activation of the digital subsystem confers on intracellular Ca(2+) signaling an exquisite architecture in space, time, and intensity, which underpins signaling efficiency, stability, specificity, and diversity. These recent advances in "sparkology" thus promise to unify the simplicity and complexity of Ca(2+) signaling in biology.
Speech enhancement based on audible noise suppression (1997)

A novel speech enhancement technique is presented based on the definition of the psychoacoustically derived quantity of audible noise spectrum and its subsequent suppression using optimal nonlinear filtering of the short-time spectral amplitude (STSA) envelope. The filter operates with sparse spectral estimates obtained from the STSA, and, when these parameters are accurately known, significant intelligibility gains, up to 40%, result in the processed speech signal. These parameters can be also estimated from noisy data, resulting into smaller but significant intelligibility gains.