gebhart/patrepeval huggingface dataset:
Design and Synthesis of Novel Derivatives of the Muscarinic Agonist Tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-Methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] Ether (CDD-0304):  Effects of Structural Modifications on the Binding and Activity at Muscarinic Receptor Subtypes and Chimeras (2006)

As part of a continuing effort to design and synthesize highly selective muscarinic agonists for different muscarinic receptor subtypes, several tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (1) analogues were prepared and characterized. Different analogues were synthesized having hydrophilic spacers of di-, tri-, tetra-, penta(ethylene glycol) and tri(propylene glycol) separating the 1,2,5,6-tetrahydropyridine ring from the terminal heterocycle, which was either a 1,2,5-thiadiazole or 1,2,4-thiadiazole ring. Chimeric receptor and molecular modeling studies also were conducted to determine how the ligands interact with muscarinic receptors. The studies revealed that varying the distance of the terminal thiadiazole and the positioning of the methoxy group can increase binding affinity for certain muscarinic receptor subtypes (at M(2) for 13d and M(4) for 1) and enhance functional efficacy at M(4) receptors for 13e and 18b. Moreover, compound 1 exhibited antipsychotic activity as assessed by reversal of apomorphine-induced sensory motor gating deficits, suggesting potential utility in the treatment of schizophrenia.
Effect of everolimus on angiogenic biomarkers in patients with tuberous sclerosis complex (TSC): Results from EXIST-1 and EXIST-2. (2012)

10619 Background: The efficacy and safety of everolimus, an oral mTOR inhibitor, was assessed in two randomized, double-blind, placebo-controlled, phase 3 trials: EXIST-1 (NCT00789828) and EXIST-2 (NCT00790400). EXIST-1 examined everolimus for the treatment of subependymal giant cell astrocytoma (SEGA) associated with TSC and EXIST-2 for the treatment of renal angiomyolipoma (AML) associated with either TSC or sporadic lymphangioleiomyomatosis. In each instance, everolimus was superior to placebo for the primary endpoints, SEGA and renal AML response rates. Inhibitors of mTOR have antiangiogenic effects on tumor growth in vitro and in vivo. Methods: Patients were randomized to receive everolimus (n=78) starting at 4.5 mg/m 2 /day (target trough, 5-15 ng/mL) or placebo (n=39) in EXIST-1 and 10 mg/day everolimus (n=79) or placebo (n=39) in EXIST-2. Plasma samples were taken at baseline and pre-dosing on day 1 of weeks 4, 12, 24, 36, and 48 of treatment. Angiogenic markers of interest were vascular endothelial growth factor (VEGF)-A and -D, placental growth factor (PlGF), soluble VEGF receptor-1 (sVEGFR1), soluble VEGF receptor 2 (sVEGFR2), c-Kit, and collagen type IV. Results: Compared with placebo, a sustained ~30% and ~60% increase in VEGF-A was observed in the everolimus arm of EXIST-1 and EXIST-2, respectively. A concomitant decrease in collagen type IV (~25% EXIST-1; ~45% EXIST-2) and sVEGFR2 (~25% both trials) was also observed in the everolimus arm. A sustained decrease (~60%) in VEGF-D was observed in the everolimus arm of EXIST-2, but not EXIST-1. In both studies, no change was observed in PlGF, sVEGFR1, or c-Kit plasma concentrations in the everolimus arm or any biomarkers evaluated in the placebo arm. Baseline sVEGFR2 and VEGF-D were ~40% and ~4-fold higher, respectively, while VEGF-A was ~50% lower in EXIST-2 compared with EXIST-1. A similar baseline plasma concentration for the other biomarkers was noted in both studies. Conclusions: Patients presenting with SEGA or renal AML associated with TSC had a reduction in plasma concentrations of sVEGFR2, collagen type IV, and VEGF-D (AML only) and an increase in VEGF-A. Everolimus may have antiangiogenic properties in TSC patients.
Spacer length shapes drug release and therapeutic efficacy of traceless disulfide-linked ADCs targeting the tumor neovasculature (2012)

We systematically investigated how the therapeutic efficacy of a traceless, vascular targeting antibody–drug conjugate (ADC) is affected by the length of a spacer introduced between the antibody's globular fold and the site of drug attachment. Homogeneous ADCs were prepared from the direct conjugation of engineered C-terminal cysteines with a potent thiol containing drug which was separated from the antibody surface by unstructured spacers of increasing length. We found that a smaller spacer length is reflected in enhanced stability and therapeutic efficacy of the conjugates in a syngeneic model of murine cancer.
Development of Region-Specific Antisera and Immunoassay for Human Prostate-Specific Antigen (PSA) with Use of Purposely Designed Synthetic Peptides (2002)

Prostate-specific antigen (PSA) itmnunoassay is now widely used in the clinical management of prostate cancer. However, the diversity of molecular forms of the protein caused the results of PSA immunoassay variable depending on specificity of the antibody used. The current study provided an efficient method for production of anti-PSA antisera strictly specific for the expected region of the molecule using purposely designed synthetic peptides. The synthetic peptides included PSA (42-92), (53"92), (50-70), (76-92), (174-184) and (199"2I0). Immunization of the peptides in rabbits afforded seventeen kinds of antisera. Binding activity to native PSA and immunohistochetnistry with human prostate proved nine of them, three anti-PSA (42-92), two anti-PSA (53"92) and four anti-PSA (50-70) antisera, to be useful for further experiment. None of antiscra against PSA (76-92) and (174-184) showed binding activity with native PSA and innnunostaining in human prostate. Using anti-PSA (53~'92) antisera with synthetic PSA (42-92) peptide as antigen and biotinyl-Gly-Gly-PSA (42-92) as labeled antigen, a novel type of PSA specific enzyme immunoassay system was successfully developed. The assay system is well defined in terms of region specificity, which is highly advantageous for its clinical use. In addition, the strict region-specificity will
Three-Dimensional Microchannels in Biodegradable Polymeric Films for Control Orientation and Phenotype of Vascular Smooth Muscle Cells (2006)

The poor mechanical strength and vasoactivity of current small-diameter tissue engineered blood vessels (TEBVs) remain unsolved problems. Given the plasticity of smooth muscle cells (SMCs), 1 of the main limitations of current scaffolding techniques is the difficulty in controlling SMC phenotype shifts in vitro. A synthetic phenotype allows the cells to rapidly proliferate and produce extracellular matrix (ECM), whereas a shift to contractile phenotype with organized ECM ultimately provides a functional blood vessel. In this study, 3D deep (65 microm) and wide microchannels separated by high-aspect ratio (8) microwalls were successfully ultraviolet (UV) microembossed using a liquid UV polymerizable biodegradable macromer (poly(epsilon-caprolactone-r-L-lactide-r-glycolide) diacrylate) and the in vitro guidance effects of varying channel width (40-160 microm) on SMCs were verified. The results show that SMCs cultured in the wider microchannels (80-160 microm wide) switch from fibroblast morphology and random orientation to spindle-shaped morphology, and align along the direction of the microchannel nearing confluence achieved with similar cell density to unpatterned film. Further, an enhanced expression of smooth muscle alpha-actin of SMCs grown on micropatterns was found nearing confluence, which demonstrates a phenotype shift to a more contractile phenotype. These films are flexible and can be folded into tubular and lamellar structures for tissue engineering of small-diameter TEBVs as well as other organs such as esophagus or intestine. These results suggest that these micropatterned synthetic biodegradable scaffolds may be useful for guiding SMCs to grow into functional, small-diameter vascular grafts.
Self-Supervised Bug Detection and Repair (2021)

Machine learning-based program analyses have recently shown the promise of integrating formal and probabilistic reasoning towards aiding software development. However, in the absence of large annotated corpora, training these analyses is challenging. Towards addressing this, we present BugLab, an approach for self-supervised learning of bug detection and repair. BugLab co-trains two models: (1) a detector model that learns to detect and repair bugs in code, (2) a selector model that learns to create buggy code for the detector to use as training data. A Python implementation of BugLab improves by up to 30% upon baseline methods on a test dataset of 2374 real-life bugs and finds 19 previously unknown bugs in open-source software.
Multi-table joins through bitmapped join indices (1995)

This technical note shows how to combine some well-known techniques to create a method that will efficiently execute common multi-table joins. We concentrate on a commonly occurring type of join known as a star-join, although the method presented will generalize to any type of multi-table join. A star-join consists of a central detail table with large cardinality, such as an orders table (where an order row contains a single purchase) with foreign keys that join to descriptive tables, such as customers, products, and (sales) agents. The method presented in this note uses join indices with compressed bitmap representations, which allow predicates restricting columns of descriptive tables to determine an answer set (or foundset ) in the central detail table; the method uses different predicates on different descriptive tables in combination to restrict the detail table through compressed bitmap representations of join indices, and easily completes the join of the fully restricted detail table rows back to the descriptive tables. We outline realistic examples where the combination of these techniques yields substantial performance improvements over alternative, more traditional query evaluation plans.
The Electrochemistry of C<sub>60</sub>Ph<sub>5</sub>Cl:  A Very Special Fullerene Derivative (2000)

C60Ph5Cl has electrochemical properties strikingly different from pristine C60: the cyclovoltammetric curves show that, in the first reduction peak, two electrons are sequentially and irreversibly injected at the same potential. Analysis of the corresponding kinetics suggests that the carbon−chlorine bond is concomitantly severed and that back-oxidation of the resulting fragments regenerates the pristine fullerene derivative. The different oxidation states of this derivative of C60 therefore repel and attract the chlorine atom, a property that further adds to the well-known special character of fullerene anions.
Approaches to Brain Stress Testing: BOLD Magnetic Resonance Imaging with Computer-Controlled Delivery of Carbon Dioxide (2012)

Background: An impaired vascular response in the brain regionally may indicate reduced vascular reserve and vulnerability to ischemic injury. Changing the carbon dioxide (CO 2 ) tension in arterial blood is commonly used as a cerebral vasoactive stimulus to assess the cerebral vascular response, changing cerebral blood flow (CBF) by up to 5-11 percent/mmHg in normal adults. Here we describe two approaches to generating the CO 2 challenge using a computer-controlled gas blender to administer: i) a square wave change in CO 2 and, ii) a ramp stimulus, consisting of a continuously graded change in CO 2 over a range. Responses were assessed regionally by blood oxygen level dependent (BOLD) magnetic resonance imaging (MRI).
Model Predictive Control of Markov Jump Linear Systems: an Error-based Self-triggered approach (2021)

This article proposes a self-triggered model predictive control algorithm for discrete-time Markov jump linear systems to fulfill computational resources saving goals. Specifically, a self-triggered scheme is presented for computing the next sampling time based on the error between the current sampled and the predicted information. The feasibility of online controller design is proved under this aperiodic sampling. Finally, a numerical example verifies the effectiveness and the resource-saving capacity of the developed approach.
Tubing For Sampling Hydrazine Vapor (1993)

Report evaluates flexible tubing used for transporting such hypergolic vapors as those of hydrazines for quantitative analysis. Describes experiments in which variety of tubing materials, chosen for their known compatibility with hydrazine, flexibility, and resistance to heat.
Case Study: Comparison of Swimsuits and Wetsuits Through Biomechanics and Energetics in Elite Female Open Water Swimmers (2021)

The wetsuit enhances submaximal swimming performance, and this increase is dependent on the OW swimmer's characteristics. The higher stroke rate and lower stroke length detected with wetsuit could be related to movement constraints imposed by the suit.
Relationship Between Noninvasive Assessment of Lung Fluid Volume and Invasively Measured Cardiac Hemodynamics (2018)

Background Right heart catheterization is the gold standard in clinical practice for the assessment of cardiovascular hemodynamics, but it is an invasive procedure requiring expertise in both insertion and reading. Remote dielectric sensing (Re DS ) is a noninvasive electromagnetic-based technology intended to quantify lung fluid content. Methods and Results In this prospective single-center study, Re DS readings were obtained in supine position just before right heart catheterization procedure in patients with heart failure. Agreement between Re DS and pulmonary artery wedge pressure ( PAWP ) was analyzed. Of all, 139 patients with heart failure received hemodynamic assessment and Re DS measurement. A good correlation was found between Re DS and PAWP measurement ( r=0.492, P<0.001). Receiver operating characteristic analysis of the ability to identify a PAWP ≥18 mm Hg resulted in a Re DS cutoff value of 34%, with an area under the curve of 0.848, a sensitivity of 90.7%, and a specificity of 77.1%. Overall, Re DS <34% carries a high negative predictive value of 94.9%. Conclusions Lung fluid content, as measured by Re DS , correlates well with PAWP . The high sensitivity and specificity and especially the high negative predictive value make Re DS a reliable noninvasive tool at the point of care, to rule out elevated PAWP in patients with heart failure and to help with medical management of patients with heart failure. Further studies are warranted to compare this tool with existing tests and to relate the findings to the clinical outcomes.
Protease-Activated Receptors (PARs) as Therapeutic Targets: Development of Agonists / Antagonists and Modulation of Gastrointestinal Functions (2004)

Protease-activated receptors (PARs), a family of G-protein-coupled seven-transmembrane-domain receptors, are activated by proteolytic unmasking of the N-terminal cryptic tethered ligand by certain serine proteases. Among four PAR family members cloned to date, PAR-1, PAR-2 and PAR-4 can also be activated through a non-enzymatic mechanism, which is achieved by direct binding of exogenously applied synthetic peptides based on the tethered ligand sequence, namely PARs-activating peptides, to the body of the receptor. Various peptide mimetics have been synthesized as agonists and / or antagonists for PARs with improved potency, selectivity and stability. The amidation of the C-terminal of PARs-activating peptides increases the potency and metabolic resistance, particularly in vivo . Substitution of the Nterminal serine residue of PAR-2-activating peptides with a furoyl group dramatically enhances both potency and metabolic resistance, providing the most potent PAR-2 agonist. Some peptide mimetics and / or non-peptide compounds have also been developed as antagonists for PAR-1 and PAR-4. PARs are widely distributed in the mammalian body, especially throughout the alimentary systems, and play various roles in physiological / pathophysiological conditions; i.e. modulation of salivary, gastric or pancreatic glandular exocrine secretion and gastrointestinal smooth muscle motility, gastric mucosal cytoprotection, suppression / facilitation of visceral pain and inflammation, etc. Thus, PARs are now considered novel therapeutic targets, and development of selective agonists and / or antagonists for PARs might provide novel strategy for clinical treatment of various diseases that are resistant to current therapeutics. Keywords: protease (proteinase)-activated receptor (par), protease, structure-activity relationship, gastrointestinal tract
Effect of Graphitized Carbon Supports on Electrochemical Carbon Corrosion in Polymer Electrolyte Membrane Fuel Cells (2009)

탄소 담지체의 결정도와 형태가 전기화학적 부식특성과 입자뭉침 현상에 미치는 영향을 평가하기 위해서on-line mass spectrometry와 cyclic voltammogram(CV)법을 사용하였다. 부식실험은 단위 전지형태에서1.4 V의 정전압 조건으로 30분간 시행되었으며 이 때 발생한 <TEX>$CO_2$</TEX> 의 양을 on-line mass spectrometry로 측정하였다. 실험 결과 결정성이 높은 carbon nanofiber (CNF)를 사용한 Pt/CNF 촉매가 결정도가 낮은 담지체를 사용한 상용 Pt/C 촉매보다 <TEX>$CO_2$</TEX> 발생량이 적어 전기화학적 부식에 대한 저항성이 큰 것으로 나타났다. 부식실험 전후의 임피던스와 CV측정에서도 탄소 부식의 영향이 적은 Pt/CNF에서 그 변화가 크지 않은 것으로 관찰되었다. 이러한 결과는 탄소 부식이 고분자 전해질형 연료전지(PEMFC)의 내구성을 결정하는 중요한 요소임을 보여준다. 하지만 탄소 부식이 영향을 미치지 않는 조건에서 실시한 반복 CV 실험 결과 촉매 입자 이동에 의한 뭉침현상은 Pt/CNF에서 더 큰 것으로 나타났다. The influence of graphitization of carbon support on the electrochemical corrosion of carbon and sintering of Pt particles are investigated by measuring <TEX>$CO_2$</TEX> emission at a constant potential of 1.4 V for 30 min using on-line mass spectrometry and cyclic voltammogram. In comparison to commercial Pt/C (from Johnson Matthey), highly graphitized carbon nanofiber (CNF) supported Pt catalyst exhibits lower performance degradation and <TEX>$CO_2$</TEX> emission. As the more carbon corrosion occurred, the more prominent changes were detected in electrochemical characteristics of fuel cell. This indicates that the carbon corrosion affects significantly the fuel cell durability. From the observed results, CNF is considered to be more corrosion resistant material as a catalyst support. However, CNF shows higher aggregation of Pt particles under repeated cyclic voltammetry between 0 and 0.8 V where the carbon corrosion is not initiated.
060 The acute haemodynamic effects of intravenous sodium nitrite in healthy volunteers during normoxia and hypoxia (2010)

<h3>Background</h3> Nitric oxide (NO) is an important endogenous paracrine vasodilator. The nitrite anion represents an alternate humoural source of NO under hypoxic and/or acidotic conditions. During hypoxia and ischaemia, the usual production of NO by NO synthase enzymes, is markedly reduced. Recently it has emerged that nitrite serves as a biological reservoir for NO under hypoxic conditions. Animal studies have shown that exogenous treatment with nitrite has important hypoxia-specific vasodilator and cytoprotective effects. Our group demonstrated that when administered intra-arterially under normoxic conditions, nitrite substantially vasodilated the venous capacitance bed, but only modestly dilated resistance human forearm vessels. In contrast during hypoxia, potent vasodilation was also observed in resistance vessels. Therefore, in this study we assessed the effects of nitrite on cardiac and peripheral haemodynamics in humans. We hypothesised that an intravenous infusion of sodium nitrite would cause a significant reduction in blood pressure during hypoxia compared to normoxia. <h3>Methods</h3> Thirty-three healthy subjects (mean age 32±10 years) were recruited. An intravenous infusion of sodium nitrite was administered at incremental doses (3, 8, 30 and 60 μmol/min) during normoxic or hypoxic conditions in random order. Hypoxia was administered by asking subjects to inspire 12% oxygen via a facemask until oxygen saturations of 83–88% were achieved. Haemodynamic measurements were determined non-invasively through the use of impedance cardiography (Taskforce<sup>®</sup>). Aplanation tonometry (SphygmoCor) was used to delineate central (aortic) blood pressure (CBP). <h3>Results</h3> To allow for the time-dependent effect of hypoxia all measurements in this group were placebo-corrected. During hypoxia, systolic blood pressure (SBP) fell by a mean of 11 mmHg (123±19 mmHg to 112±15 mmHg, p≤0.05) from baseline during peak nitrite dose. There was a non-significant reduction in SBP during normoxia of 6 mmHg (120±13 mmHg to 114±22 mmHg, p=NS). No significant changes were observed in stroke volume or cardiac output in either group. In the hypoxia group, total peripheral resistance mirrored changes in SBP. CBP fell in both groups (9 vs13 mmHg, normoxia vs hypoxia, p=NS) from baseline. No significant changes were observed in parameters between the normoxia and hypoxia group. <h3>Conclusion</h3> An acute intravenous infusion of nitrite was safe and well tolerated in healthy volunteers. A significant decrease in blood pressure was observed during hypoxia, but not during normoxia, thus supporting the role of nitrite as a hypoxia-specific vasodilator.
Walk-off effects in dual-pump parametric amplifiers (2004)

The noise figure of fiber-based parametric amplifiers is affected by intensity fluctuations associated with the pumps. We show that the effects of walk off between the signal and pumps help to improve the noise figure of dual-pump parametric amplifiers in the central flat region of the gain spectrum.
Thermomechanical Stabilization of Electron Small Polarons in SrTiO₃ Assessed by the Quasiharmonic Approximation (2017)

We predict a predominance diagram for electron defects in the temperature-hydrostatic stress space for SrTiO₃ by combining density functional theory and the quasiharmonic approximation. We discovered two regimes where small polarons dominate: under tensile stress at lower temperature due to a larger relaxation volume of the defect Ω, and under compressive stress at higher temperature due to a smaller Ω and larger formation entropy. This provides a means to modulate the electronic conductivity via controlling the underlying charge carrier. Furthermore, the results challenge the common association between larger Ω and charge localization by demonstrating that at high temperature the free electron can induce larger Ω compared to the small polaron. This finding is attributed to the ability of the free electron to generate greater vibrational entropy upon finite isothermal expansion.
ChemInform Abstract: Novel Bacterial Triterpenoids of the Hopane Series from Nitrosomonas europaea and Their Significance for the Formation of the C<sub>35</sub> Bacteriohopane Skeleton. (1999)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.