gebhart/patrepeval huggingface dataset:
Novel Vanilloid Receptor-1 Antagonists:  3. The Identification of a Second-Generation Clinical Candidate with Improved Physicochemical and Pharmacokinetic Properties (2007)

Based on the previously reported clinical candidate, AMG 517 (compound 1), a series of related piperazinylpyrimidine analogues were synthesized and evaluated as antagonists of the vanilloid 1 receptor (VR1 or TRPV1). Optimization of in vitro potency and physicochemical and pharmacokinetic properties led to the discovery of (R)-N-(4-(6-(4-(1-(4-fluorophenyl)ethyl)piperazin-1-yl)pyrimidin-4-yloxy)benzo[d]thiazol-2-yl)acetamide (16p), a potent TRPV1 antagonist [rTRPV1(CAP) IC50 = 3.7 nM] with excellent aqueous solubility (>or=200 microg/mL in 0.01 N HCl) and a reduced half-life (rat t1/2 = 3.8 h, dog t1/2 = 2.7 h, monkey t1/2 = 3.2 h) as compared to AMG 517. In addition, compound 16p was shown to be efficacious at blocking a TRPV1-mediated physiological response in vivo (ED50 = 1.9 mg/kg, p.o. in the capsaicin-induced flinch model in rats) and was also effective at reducing thermal hyperalgesia induced by complete Freund's adjuvant in rats (MED = 1 mg/kg, p.o). Based on its improved overall profile, compound 16p (AMG 628) was selected as a second-generation candidate for further evaluation in human clinical trials as a potential new treatment for chronic pain.
N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why (2018)

The main molecular mechanisms explaining the well-established antioxidant and reducing activity of N-acetylcysteine (NAC), the N-acetyl derivative of the natural amino acid l-cysteine, are summarised and critically reviewed. The antioxidant effect is due to the ability of NAC to act as a reduced glutathione (GSH) precursor; GSH is a well-known direct antioxidant and a substrate of several antioxidant enzymes. Moreover, in some conditions where a significant depletion of endogenous Cys and GSH occurs, NAC can act as a direct antioxidant for some oxidant species such as NO<sub>2</sub> and HOX. The antioxidant activity of NAC could also be due to its effect in breaking thiolated proteins, thus releasing free thiols as well as reduced proteins, which in some cases, such as for mercaptoalbumin, have important direct antioxidant activity. As well as being involved in the antioxidant mechanism, the disulphide breaking activity of NAC also explains its mucolytic activity which is due to its effect in reducing heavily cross-linked mucus glycoproteins. Chemical features explaining the efficient disulphide breaking activity of NAC are also explained.
Aqueous Synthesis of Y <sub>2</sub> O <sub>2</sub> S:Eu/Silica Core‐Shell Particles (2005)

A layer‐by‐layer method is used to coat silica on the red phosphor powders of Y 2 O 2 S:Eu in aqueous solutions. A cationic polymer of polyethylenimine (PEI) is used to form the first‐layer coating, and the precipitating sodium silicate solution, to form negatively charged silica film on the PEI‐coated phosphor powder as the second‐layer coating. Repetition of the above coating process in aqueous solutions, a uniform, multiple silica/PEI bilayer coating on phosphor powder is formed.
Modular Java web applications (2008)

As Java EE applications increase in size and complexity the constraints imposed by the existing component model restrict their utility. In this paper, we describe a solution to the problem related to building modular and evolvable server-side applications in Java. We use Eclipse's OSGi runtime as a basis for solving the problem and describe its integration in a Java EE Application Server environment.
Explication: The Cratylus (1991)

Plato’s Cratylus is a dialogue on language involving Cratylus, Hermogenes, and Socrates. The issue at hand involves the correctness and truth in names and whether modification of names changes their meaning. This paper reflects on how the Cratylus presents Socrates’s argument and then goes on to suggest that Plato’s description of Socrates’s use of myth suggests that he was subtly pointing out the human-like quality of gods and the godlike qualities of man. For Plato all of this is framed and informed by the discussion of truth in naming.
Production of antibodies that bind biotin and inhibit biotin containing enzymes (1975)

Methods were developed for the coupling of biotin to bovine serum albumin and bovine gamma-globulin using a water-soluble carbodimide. The use of [14-C]biotin as a tracer allowed quantitation of the incorporation of biotin into the conjugates: 2.55 mol of biotin was incorporated per mol of gamma-globulin and 7-9 mol of biotin was incorporated per mol of serum albumin in different preparations. These conjugates were highly immunogenic in the rabbit and anti-bodies reactive with the biotinyl group itself could be detected by their ability to precipitate the heterologous biotinated carrier but not the unmodified heterologous carrier. There antisera rapidly inactivated transcarboxylase and pyruvate carboxylase and this inactivation could be blocked by pretreatment of the antisera with biotin or biocytin. Using enzyme inhibition to detect free antibody, the binding constant for biotin was found to be 5.0 x 10- minus 8 M and that for biocytin 3.5 x 10- minus 8 M.
Characterization of Defects in Graphite Fiber Based Composite Structures Using the Acoustic Impact Technique (AIT) (1993)

Abstract Acoustic Impact Technique (AIT), commonly known as “coin-tapping,” has been applied by previous investigators as a nondestructive evaluation technique to study disbonds in composite honeycomb structures. The experimental configuration adopted by previous investigators was somewhat restricted. In this study, a different approach to AIT is developed. This was done to overcome the experimental constraints encountered in the previous approaches. This paper presents experimental results obtained in the evaluation of defects commonly found in graphite based composite structures, such as delamination, fiber breakage, and misaligned fibers. The experimental approach adopted in this work has two main features. Primarily, the force-time history of the specimen's response to a low magnitude input pulse in different regions of the specimen is compared. Secondly, an Acoustic Emission (AE) wide band sensor was used in conjunction with the conventional acoustic impact technique. The combination of the AE sensor and AIT enabled the study of the material interaction with stress waves generated in the vicinity of the tapped region. Gross defects such as delaminations were identified through the change in the pulse width of the force input, while defects such as fiber breakage and misaligned fibers were successfully identified using AIT in conjunction with AE.
Anti-hyperglycemic Potential of Natural Products (2006)

In order to evaluate the anti-hyperglycemic effect of natural compounds via the inhibition of alpha-glucosidase (AGH), the potential inhibitory effect of anthocyanins, caffeic acid analogs, and caffeoylquinic acid analogs have been reviewed. A new AGH assay system to mimic the membrane-bound AGH at the small intestine was proposed and evaluated.
Human immunodeficiency virus and acquired immunodeficiency syndrome: an update. (1994)

Research progress in the understanding of HIV and its effects on the human immune system continues at a rapid pace. Such research is yielding new ideas for chemotherapeutic agents, immunologic stimulators and modifiers, and potential vaccines. Clinical trials to test these approaches are under way. Despite the accomplishments, the epidemic progresses unchecked, resulting in continued suffering and death and enormous demands on the health care system of many nations. Clinicians have had to deal with new and difficult opportunistic infections. Yet advances in the treatment and prevention of these illnesses have benefited many AIDS victims. In the United States, the AIDS epidemic is now concentrating in the inner cities, involving injection drug users, minorities, heterosexuals, women and their offspring. In the developing world, AIDS continues to be predominantly a heterosexually transmitted disease, where more than one third of prostitutes in central African cities are infected. The major burden of the AIDS epidemic in the remainder of this and the next century will be in India and Southeast Asia, again predominantly via heterosexual spread. A great deal is now understood concerning the life cycle of HIV. More light has been shed on the interaction of HIV and CD4+ T cells, the cellular and viral factors involved in viral expression vs. latency, the function of the viral regulatory and structural proteins and the role of cytokines in regulation of HIV expression. Our understanding of the precise mechanisms whereby HIV causes a loss of CD4+ T cells remains incomplete. The direct infection and cell killing of CD4+ T cells is important and is supported by recent evidence demonstrating a high viral burden in these cells in the lymphoid tissue of patients. Over the last 1 to 2 years, there has been new evidence for indirect mechanisms of CD4+ T-cell depletion and/or dysfunction including: autoimmune reactions, perturbations of specific V beta T-cell receptor populations, infection of T-cell precursors in bone marrow and thymus, immunosuppression and dysregulation by viral proteins, possible super-antigen effects, and antigen-induced apoptosis or programmed cell death. New information has come forth in our understanding of B-cell abnormalities in HIV pathogenesis, including the putative role of IL-6 in B-cell activation and the identification of EBV in B-cell lymphomas in the CNS of patients with AIDS. It is expected that these and future discoveries concerning immunopathogenesis of HIV infection will help steer the therapeutic effort. Major strides continue to be made in the therapeutic arena for HIV infection and its complications.(ABSTRACT TRUNCATED AT 400 WORDS)
Mononuclear Molybdenum(IV) Complexes with Two Multiply Bonded Chalcogen Ligands in Trans Configuration and Chelating Biphosphine Ligands (1997)

A series of molybdenum(IV) complexes of the type trans-Mo(Q)(Q')(P&arcraise;P)(2) has been prepared where Q and Q' are chalcogen ligands (O, S, Se, Te) and P&arcraise;P is either cis-1,2-bis(diphenylphosphino)ethylene (dppee) or 1,2-bis(diphenylphosphino)ethane (dppe). X-ray crystallographic studies were carried out to investigate how the Mo-Q distance is influenced by the mutually competitive d(pi)-p(pi) interactions between the p(x)() and p(y)() orbitals of the chalcogen ligands and the d(xz)() and d(yz)() orbitals of the molybdenum center. trans-Mo(O)(2)(dppee)(2) (1) has been prepared by the hydrolysis and deprotonation reaction of [Mo(O)(Cl)(dppee)(2)]Cl with NaOH in methanol. The compounds where Q represents the heavier chalcogens (S, Se, Te) have been prepared by the reaction between trans-Mo(N(2))(2)(P&arcraise;P)(2) and a chalcogen source: trans-Mo(S)(2)(dppee)(2) (2), BzS(3)Bz (dibenzyl trisulfide); trans-Mo(Se)(2)(dppee)(2) (3), elemental Se; trans-Mo(Te)(2)(dppee)(2) (4), TePEt(3) (Et = ethyl); trans-Mo(S)(2)(dppe)(2) (5), BzS(3)Bz; trans-Mo(Se)(2)(dppe)(2) (6), Se. trans-Mo(O)(S)(dppee)(2) (7) was obtained from the reaction of MoCl(3)(THF)(3) (THF = tetrahydrofuran), dppee, and NaHS in a mixture of THF and methanol. The attempted preparation of 7 by the reaction of SO(2) and trans-Mo(N(2))(2)(dppee)(2) yielded Mo(SO(2))(2)(dppee)(2) (8). 1 crystallizes in the monoclinic space group P2(1)/c (No. 14, Z = 2) with a = 11.1340(15) Å, b = 18.435(2) Å, c = 12.515(2) Å, and beta = 110.999(9) degrees; 2 crystallizes in the triclinic space group P&onemacr; (No. 2, Z = 1) with a = 10.102(4) Å, b = 10.722(4) Å, c = 12.195(3) Å, alpha = 100.95(3) degrees, beta = 95.04(4) degrees, and gamma = 117.81(2) degrees; 3 crystallizes in the monoclinic space group P2(1)/c (No. 14, Z = 2) with a = 11.186(5) Å, b = 18.005(8) Å, c = 12.761(9) Å, and beta = 110.35(4) degrees; 4 crystallizes in the triclinic space group P&onemacr; (No. 2, Z = 2) with a = 12.681(4) Å, b = 19.280(5) Å, c = 10.454(3) Å, alpha = 104.60(2) degrees, beta = 111.61(2) degrees, and gamma = 75.12(2) degrees; 5 crystallizes in the monoclinic space group C2/c (No. 15, Z = 8) with a = 49.515(7) Å, b = 10.9286(12) Å, c = 18.203(3) Å, and beta = 98.306(12) degrees; 6 crystallizes in the monoclinic space group C2/c (No. 15, Z = 8) with a = 49.566(9) Å, b = 10.9765(15) Å, c = 18.282(3) Å, and beta = 98.541(13) degrees; 7 crystallizes in the triclinic space group P&onemacr; (No. 2, Z = 1) with a = 10.040(1) Å, b = 10.563(1) Å, c = 12.162(2) Å, alpha = 75.30(1) degrees, beta = 85.93(1) degrees, and gamma = 63.21(1) degrees; 8 crystallizes in the monoclinic space group C2/c (No. 15, Z = 4) with a = 21.534(6) Å, b = 12.4271(13) Å, c = 19.550(5) Å, and beta = 118.480(14) degrees. The UV/vis and the (31)P{(1)H} NMR data for compounds 1-7 are also reported and discussed.
Urinary nerve growth factor but not prostaglandin E2 increases in patients with interstitial cystitis/bladder pain syndrome and detrusor overactivity (2009)

Urinary NGF/Cr levels are elevated in women with IC/BPS or DO, but not in those with IBS. The differential diagnosis of women with IC/BPS from those with frequency-urgency syndrome is possible based on urinary NGF/Cr levels but not urinary PGE2/Cr level.
Clinical Interpretation of Airway Response to a Bronchodilator: Epidemiologic Considerations (1988)

Airways responsiveness to a bronchodilator is frequently measured to assist in determining the cause of respiratory symptoms. Clinically, a greater than 15% improvement in the FEV1 is often used to define the "increased" response indicative of asthma. However, unlike other tests of lung function, reference standards derived from "healthy" members of a general population sample have never been reported. As part of a health survey carried out in Alberta, Canada, 2,609 subjects completed a standardized respiratory symptom questionnaire and had FEV1 measured before and 20 min after inhaling terbutaline sulfate via a 750-ml spacer device. Among asymptomatic never-smoking subjects with a FEV1 greater than 80% of predicted, the upper 95th percentile of bronchodilator response (BDR), when expressed as 100 x (FEV1 postBDR - FEV1 preBDR)/predicted baseline FEV1 averaged 9%. This value remained remarkably stable across gender, age (7 to 75 yr), and height groups, and deviated to 6% only when baseline FEV1 was greater than 120% of predicted. Consistent with other respiratory function variables, in which the upper limit of normal is often defined as the upper 95th percentile, our population-derived reference values provide a conceptual definition of BDR that can easily be applied to define "increased" response in the clinical setting.
α <sub>4</sub> β <sub>1</sub> Integrin Activation of L-Type Calcium Channels in Vascular Smooth Muscle Causes Arteriole Vasoconstriction (2002)

A pathway for the regulation of vascular tone appears to involve coupling between integrins and extracellular matrix proteins or their fragments and the subsequent modulation of ion movement across the smooth muscle cell membrane. Here, we report that the activation of L-type voltage-activated Ca(2+) channels occurs through a novel interaction of alpha(4)beta(1) integrin with peptides containing the Leu-Asp-Val (LDV) integrin--binding sequence, which is found in the CS-1 region of an alternately spliced fibronectin variant. Experiments were conducted on arterioles isolated from rat skeletal muscle. Arterioles exhibited sustained concentration-dependent vasoconstriction to LDV peptides but not to Leu-Glu-Val (LEV) control peptides. The constriction was associated with increased smooth muscle cell [Ca(2+)](i), as measured by using fura 2. The response could be inhibited with a function-blocking anti--alpha(4) integrin antibody. Removal of the endothelium did not alter the vasoconstrictor response. Further experiments demonstrated that the vasoconstriction was abolished by the L-type Ca(2+) channel inhibitor nifedipine and the Src family kinase inhibitor PP2. In studies of isolated smooth muscle cells using whole-cell patch-clamp methods, the L-type current was enhanced by the LDV but not LEV peptide and was blocked by PP2 or antibodies to alpha(4) integrin. Collectively, these data indicate that activation of alpha(4)beta(1) integrin leads to enhanced influx of Ca(2+) through L-type channels by activating a tyrosine kinase pathway, leading to vasoconstriction. Involvement of integrins in the modulation of vascular tone may be particularly important in vascular responses to mechanical signals, such as pressure and flow, and to tissue injury after damage to the extracellular matrix.
Photoplethysmography-Based Heart Rate Monitoring Using Asymmetric Least Squares Spectrum Subtraction and Bayesian Decision Theory (2015)

Motion artifacts (MAs) are strong interference sources in wearable photoplethysmography (PPG) signals, significantly affecting estimation of heart rate (HR) and other physiological parameters. In this paper, a novel method called SPECTRAP is proposed for accurate motion-tolerant estimation of HR using a PPG signal and a simultaneous acceleration signal. The method first calculates the spectra of the PPG signal and the acceleration signal, and then removes the MA spectral components from the PPG spectrum using a new spectrum subtraction algorithm. The new spectrum subtraction algorithm is based on asymmetric least square and overcomes drawbacks of the conventional spectrum subtraction algorithms. To find the spectral peak corresponding to HR on the resulting spectrum, SPECTRAP formulates the problem into a pattern classification problem and uses the Bayesian decision theory to solve it. Experimental results on the PPG database used in 2015 IEEE Signal Processing Cup showed that the proposed algorithm has excellent performance. The average absolute error on the twelve training sets was 1.50 beat per minute (BPM) (standard deviation: 1.95 BPM). The average absolute error on the ten testing sets was 2.13 BPM (standard deviation: 2.77 BPM).
Spatial smoothing and hot spot detection for CGH data using the fused lasso (2007)

We apply the "fused lasso" regression method of (TSRZ2004) to the problem of "hot- spot detection", in particular, detection of regions of gain or loss in comparative genomic hybridization (CGH) data. The fused lasso criterion leads to a convex optimization problem, and we provide a fast algorithm for its solution. Estimates of false-discovery rate are also provided. Our studies show that the new method generally outperforms competing methods for calling gains and losses in CGH data.
DNMT cooperativity—the developing links between methylation, chromatin structure and cancer (2003)

Controversy has reigned for some time over the biological connection between DNA methylation and cancer. For this reason, the methylation mechanism responsible for increased cancer risk has received greater attention in recent years. Tumor suppressor genes are often hypermethylated resulting in gene silencing. Although some have questioned this interpretation of the link between methylation and cancer, it appears that both hypermethylation and hypomethylation events can create epigenetic changes that can contribute to cancer development. Recent studies have shown that the methyltransferases DNMT1 and DNMT3b cooperatively maintain DNA methylation and gene silencing in human cancer cells. Disruption of the human DNMT3b only slightly reduces the overall global DNA methylation; however, demethylation was markedly potentiated when both DNMT1 and DNMT3b were simultaneously deleted. The results to these experiments provide compelling evidence towards a role for DNA methylation in cancer. This review discusses the current understanding of cancer-epigenetic information and highlights recent studies that connect the methylation machinery and chromatin remodelling with cancer susceptibility.
Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt‐dependent mechanisms (2008)

Resveratrol delayed the onset of EPC senescence and this effect was accompanied by activation of telomerase through the PI3K-Akt signalling pathway. The inhibition of EPCs senescence by resveratrol might protect EPCs against dysfunction induced by pathological factors in vivo and improve EPC functional activities in a way that may be important for cell therapy.
Production of aflatrem and its related indoloditerpenes by microsclerotium-producing strains of Aspergillus flavus (1989)

The production of aflatrem and its related indoloditerpene metabolites by microsclerotium-producing strains of Aspergillus flavus was investigated. Four strains of atypical A. flavus isolated from Indonesian traditional medicines (native name, “Jamu”) and three representative strains of the same fungus obtained from the Northern Regional Research Center, USDA were cultured on Czapek-Yeast extract Agar at 34°C and the amounts of tremorgenic mycotoxins, aflatrem and seven related indoloditerpenes, were measured by high-performance liquid chromatography with a UV detector. All the strains examined produced aflatrem and dihydroxyaflavinine. The concentrations of them were ranged from 149 to 3, 009 and 1, 092 to 35, 629μg/g of the dried sclerotia, respectively. Aflavinine, monohydroxyaflavinine, monohydroxyisoaflavinine, paspaline, paspalinine and emindole SB were detected in the sclerotia of A. flavus. This is the first report on the production of emindole SB and paspaline by A. flavus.
Interference mitigation study for uwb impulse radio (2004)

This paper discusses the reduction of interference from coexisting narrowband signal to UWB impulse radio. Two countermeasure techniques are proposed to reduce interference from narrowband signals on only the receiver side. One is to use a filter that rejects the interference signals. The second is to use modified template waveform at the receiver correlation. We propose to use multi-carrier type template waveform that has 11-sub-carrier pulses. When there are some interferers, it is possible to reduce the effect of the interferers by using a modified template waveform that is constructed with the multi-carrier type template removing some sub-carrier pulses that are close to the interfering spectrum. We show that the bit error rate performance is improved by the multi-carrier template.
Podocytes in glomerulus of rat kidney express a characteristic 44 KD protein. (1991)

We describe a new monoclonal antibody (MAb) directed against glomerular visceral epithelial cells (podocytes), generated by immunization with isolated rat kidney glomeruli. In immunoblotting experiments this MAb (IgG1 subclass) reacted with a 44 KD protein. In cryostat sections of normal rat kidney the MAb stained glomerular podocytes; therefore, we called the antigen pp44 (podocyte protein 44 KD). On 0.5-micron cryostat sections the signal could be more precisely ascribed to the podocyte foot processes, whereas the cell bodies appeared virtually unreactive. On ultra-thin frozen sections pp44 was found within the cytoplasm of podocyte foot processes at their origin from their parent processes. The podocyte cell membrane was not labeled. All other parts of the nephron were unreactive. An additional but weaker immunoreaction was found in the arterial endothelium; the endothelia of other vessels (peritubular capillaries, veins) were negative. In human kidney anti-pp44 revealed the same staining pattern as in rat kidney. The expression of pp44 was also studied in newborn rat kidney. The early stages of glomerular development (renal vesicle, S-shaped body) were negative. pp44 first appeared during the capillary loop stage, i.e., when formation of podocyte foot processes commences. In comparing the present results with published data, pp44 is clearly different from other antigens thus far described in podocytes. From the results of this investigation we conclude that pp44 represents a novel cytoplasmic protein of podocytes. Our data suggest a cytoskeletal role for pp44 in preserving the complex architecture of podocytes. This idea is confirmed by the simultaneous appearance of foot processes and anti-pp44 immunoreactivity during glomerular development.