gebhart/patrepeval huggingface dataset:
2-Aminopyridines with a Truncated Side Chain To Improve Human Neuronal Nitric Oxide Synthase Inhibitory Potency and Selectivity (2015)

We have analyzed a recently obtained crystal structure of human neuronal nitric oxide synthase (nNOS) and then designed and synthesized several 2-aminopyridine derivatives containing a truncated side chain to avoid the hydrophobic pocket that differentiates human and rat nNOS in an attempt to explore alternative binding poses along the substrate access channel of human nNOS. Introduction of an N-methylethane-1,2-diamine side chain and conformational constraints such as benzonitrile and pyridine as the middle aromatic linker were sufficient to increase human and rat nNOS binding affinity and inducible and endothelial NOS selectivity. We found that 14b is a potent inhibitor; the binding modes with human and rat nNOS are unexpected, inducing side chain rotamer changes in Gln478 (rat) at the top of the active site. Compound 19c exhibits Ki values of 24 and 55 nM for rat and human nNOS, respectively, with 153-fold iNOS and 1040-fold eNOS selectivity. 19c has 18% oral bioavailability.
Cytosolic phospholipase A2α gene silencing in monocytes alters development of Th1 responses and reduces autoimmune arthritis (2010)

International audience
Contour Generation with Realistic Inter-observer Variation (2022)

Contours are used in radiotherapy treatment planning to identify regions to be irradiated with high dose and regions to be spared. Therefore, any contouring uncertainty influences the whole treatment. Even though this is the biggest remaining source of uncertainty when daily IGRT or adaptation is used, it has not been accounted for quantitatively in treatment planning. Using probabilistic planning allows to directly account for contouring uncertainties in plan optimisation. The first step is to create an algorithm that can generate many realistic contours with variation matching actual inter-observer variation. We propose a methodology to generate random contours, based on measured spatial inter-observer variation, IOV, and a single parameter that controls its geometrical dependency: alpha, the width of the 3D Gaussian used as point spread function (PSF). We used a level set formulation of the median shape, with the level set function defined as the signed distance transform. To create a new contour, we added the median level set and a noise map which was weighted with the IOV map and then convolved with the PSF. Thresholding the level set function reconstructs the newly generated contour. We used data from 18 patients from the golden atlas, consisting of five prostate delineations on T2-w MRI scans. To evaluate the similarity between the contours, we calculated the maximum distance to agreement to the median shape (maxDTA), and the minimum dose of the contours using an ideal dose distribution. We used the two-sample Kolmogorov-Smirnov test to compare the distributions for maxDTA and minDose between the generated and manually delineated contours. Only alpha=0.75cm produced maxDTA and minDose distributions that were not significantly different from the manually delineated structures. Accounting for the PSF is essential to correctly simulate inter-observer variation.
Enhanced oxidation of volatile organic compounds from flue gases using hydrogen peroxide (1995)

The destruction of certain hazardous volatile organic compounds (VOCs) by incineration requires high temperatures and long residence times. It was postulated that the addition of a radical source, such as hydrogen peroxide, to a heated stream of VOCs in air would enhance the kinetics of thermal oxidation. The VOCs studied included n-heptane and chlorobenzene. Several temperatures, residence times, and concentrations of hydrogen peroxide were tested for each compound. Results show that hydrogen peroxide is effective in enhancing destruction and removal efficiency for both compounds tested. However, there were marked differences in the hydrogen peroxide concentrations and temperatures required for similar effects. These differences led to further experiments investigating the reaction pathways. Computer kinetic modeling packages (Chemkin II) were generated for each compound. The concentration profiles of the parent compounds were compared to the experimentally determined destruction efficiency with good agreement. The products of incomplete combustion from the experiments were identified and quantified. Although the model did not accurately predict products of incomplete combustion for both systems, the experimental data provides information for further adjustment of the model and a better understanding of what reactions may be of importance in the proposed mechanisms.
.alpha.-Conotoxins, small peptide probes of nicotinic acetylcholine receptors (1991)

alpha-Conotoxins, a family of small peptides from the venoms of the Conus marine moluscs, are selective, snake alpha-neurotoxin-competitive antagonists of the nicotinic acetylcholine receptor. A new alpha-conotoxin, SIA, has been purified, sequenced, and synthesized. Cross-linking with bivalent reagents and photoaffinity labeling of the acetylcholine receptor with alpha-conotoxin yield covalent adducts. Surprisingly, cross-linking to other subunits is considerably more efficient than to the alpha subunit. The relative efficiency of photoactivatable cross-linking to different subunits of the receptor is a function of placement of the photoactivatable group on the toxin. Since the structures of alpha-conotoxins can be solved by 2D NMR [see Pardi et al. (1989) Biochemistry 28, 5494-5508; Kobayashi et al. (1989) Biochemistry 28, 4853-4860], this family of toxins should provide a set of new ligands for probing the acetylcholine receptor with considerable precision.
Survivorship Beyond Convalescence: 48-Month Quality-of-Life Outcomes After Treatment for Localized Prostate Cancer (2009)

Decision making for treatment of localized prostate cancer is often guided by therapeutic side-effect profiles. We sought to assess health-related quality-of-life outcomes for patients 48 months after treatment for localized prostate cancer. Men treated for localized prostate cancer (N = 475) were evaluated before treatment and at 11 intervals during the 48 months after intervention. Changes in mean health-related quality-of-life scores and the probability of regaining baseline levels of health-related quality of life were compared between treatment groups. All statistical tests were two-sided. Urinary incontinence was more common after prostatectomy (n = 307) than after brachytherapy (n = 90) or external beam radiation therapy (n = 78) (both P < .001), whereas voiding and storage urinary symptoms were more prevalent after brachytherapy than after prostatectomy (both P < .001). Sexual dysfunction profoundly affected all three treatment groups, with a lower likelihood of regaining baseline function after prostatectomy than after external beam radiation therapy or brachytherapy (P < .001). Bowel dysfunction was more common after either form of radiation therapy than after prostatectomy. These results may guide decision making for treatment selection and clinical management of patients with health-related quality-of-life impairments after treatment for localized prostate cancer.
Data sharing barriers and enablers for healthcare Artificial Intelligence (AI) in Low- and Middle-income countries (2023)

Population Medicine considers the following types of articles:• Research Papers -reports of data from original research or secondary dataset analyses.• Review Papers -comprehensive, authoritative, reviews within the journal's scope.These include both systematic reviews and narrative reviews.• Short Reports -brief reports of data from original research.• Policy Case Studies -brief articles on policy development at a regional or national level.• Study Protocols -articles describing a research protocol of a study.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.• Methodology Papers -papers that present different methodological approaches that can be used to investigate problems in a relevant scientific field and to encourage innovation.
Optical erasure of holograms in lithium niobate crystals (1978)

In this paper we intend to present an experimental investigation of a volume phase hologram erasure under stationary optical illumination.
Cure Studies of PMDA-ODA- and BTDA-ODA-Based Polyimides by Fluorescence Spectroscopy (1989)

The effect of thermal curing on the morpholgy and conformation of PMDA-ODA and BTDA-ODA polyimides is investigated using fluorescence spectroscopy. These polyimides are found to exhibit intrinsic fluorescence. This fluorescence arises as a result of excitation in either of two spectral bands. Emission from a single chromophore is observed and the two excitation bands are described in terms of both an intra- and an intermolecular charge transfer complex (CTC). The intra-CTC is ascribed to rotation around the imide nitrogen-phenyl bond. The inter-CTC arises as a result of the increase in aggregation associated with a more ordered phase. The emission intensity from excitation of the inter-CTC band increases linearly with reciprocal intermolecuar spacing.
Black phosphorus incorporation modulates nanocomposite hydrogel properties and subsequent MC3T3 cell attachment, proliferation, and differentiation (2021)

A promising strategy that emerged in tissue engineering is to incorporate two-dimensional (2D) materials into polymer scaffolds, producing materials with desirable mechanical properties and surface chemistries, which also display broad biocompatibility. Black phosphorus (BP) is a 2D material that has sparked recent scientific interest due to its unique structure and electrochemical characteristics. In this study, BP nanosheets (BPNSs) were incorporated into a cross-linkable oligo[poly(ethylene glycol) fumarate] (OPF) hydrogel to produce a new nanocomposite for bone regeneration. BPNSs exhibited a controllable degradation rate coupled with the release of phosphate in vitro. MTS assay results together with live/dead images confirmed that the introduction of BPNSs into OPF hydrogels enhanced MC3T3-E1 cell proliferation. Moreover, the morphology parameters indicated better attachments of cells in the BPNSs containing group. Immunofluorescence images as well as intercellular ALP and OCN activities showed that adding a certain amount of BPNSs to OPF hydrogel could greatly improve differentiation of pre-osteoblasts on the hydrogel. Additionally, embedding black phosphorous into a neutral polymer network helped to control its cytotoxicity, with optimal cell growth observed at BP concentrations as high as 500 ppm. These results reinforced that the supplementation of OPF with BPNSs can increase the osteogenic capacity of polymer scaffolds for use in bone tissue engineering.
Ureteroscopy for Pediatric Urolithiasis: An Evolving First-Line Therapy (2005)

No AccessJournal of UrologyUrological Survey: Urolithiasis, Endourology and Laparoscopy1 Oct 2005Ureteroscopy for Pediatric Urolithiasis: An Evolving First-Line Therapy Ralph V. ClaymanM.D. Ralph V. ClaymanRalph V. Clayman More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000175880.55622.c6AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Ureteroscopy for Pediatric Urolithiasis: An Evolving First-Line Therapy." The Journal of Urology, 174(4 Part 1), pp. 1447–1448 © 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 174Issue 4 Part 1October 2005Page: 1447-1448 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.MetricsAuthor Information Ralph V. Clayman More articles by this author Expand All Advertisement Loading ...
Evaluation of accelerated stability test conditions for medicated chewing gums (2012)

The overall stability of medicated chewing gums is investigated under different storage conditions. Active substances with different chemical stabilities in solid state are chosen as model drugs. The dosage form is a three layer tablet obtained by direct compression. The gum core contains the active ingredient while the external layers are formulated to prevent gum adhesion to the punches of the tableting machine. Two accelerated test conditions (40°C/75% RH and 30°C/65% RH) are performed for 6 months. Furthermore, a long-term stability test at room conditions is conducted to verify the predictability of the results obtained from the stress tests. Some drugs are stable in all the conditions tested, but other drugs, generally considered stable in solid dosage forms, have shown relevant stability problems particularly when stress test conditions are applied to this particular semi-solid dosage forms. For less stable drugs, the stress conditions of 40°C/75% RH are not always predictable of chewing gum stability at room temperature and may produce false negative; intermediate conditions, 30°C/65% RH, are more predictive for this purpose, the results of drug content found after 6 months at intermediate stress conditions and 12 months at room conditions are generally comparable. But the results obtained show that only long-term conditions stability tests gave consistent results. During aging, the semi solid nature of the gum base itself, may also influence the drug delivery rate during chewing and great attention should be given also to the dissolution stability.
Inhibitors of Nav1.7 for the Treatment of Pain (2022)

ADVERTISEMENT RETURN TO ISSUEPREVPatent HighlightNEXTInhibitors of Nav1.7 for the Treatment of PainBenjamin E. Blass*Benjamin E. BlassSchool of Pharmacy, Moulder Center for Drug Discovery Research, Department of Pharmaceutical Sciences, Temple University, Philadelphia, Pennsylvania 19140, United States*[email protected]More by Benjamin E. Blasshttps://orcid.org/0000-0003-2449-4503Cite this: ACS Med. Chem. Lett. 2022, 13, 4, 532–533Publication Date (Web):March 22, 2022Publication History Received27 February 2022Published online22 March 2022Published inissue 14 April 2022https://pubs.acs.org/doi/10.1021/acsmedchemlett.2c00088https://doi.org/10.1021/acsmedchemlett.2c00088editorialACS PublicationsCopyright © Published 2022 by American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views2804Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (767 KB) Get e-AlertscloseSUBJECTS:Alkyls,Carbon,Inhibitors,Neurophysiology,Phenyls Get e-Alerts
Accuracy of the Krieger-Li-Iafrate approximation for molecules (2000)

Accurate electronic structure calculations for diatomic molecules have been performed, using the Krieger-Li-Iafrate (KLI) approximation to the optimized potential method (OPM) for the evaluation of the exact exchange potential of density-functional theory. It is found that the KLI scheme provides an excellent approximation to the full OPM for these systems. The deviations between both variants of the OPM are smaller than the differences resulting from the use of different basis sets. Furthermore, it is shown that the spectroscopic constants obtained with the exchange-only KLI approach are very close to Hartree-Fock values.
Poliovirus mutant that does not selectively inhibit host cell protein synthesis. (1985)

A poliovirus type I (Mahoney strain) mutant was obtained by inserting three base pairs into an infectious cDNA clone. The extra amino acid encoded by the insertion was in the amino-terminal (protein 8) portion of the P2 segment of the polyprotein. The mutant virus makes small plaques on HeLa and monkey kidney (CV-1) cells at all temperatures. It lost the ability to mediate the selective inhibition of host cell translation which ordinarily occurs in the first few hours after infection. As an apparent consequence, the mutant synthesizes far less protein than does wild-type virus. In mutant-infected CV-1 cells enough protein was produced to permit a normal course of RNA replication, but the yield of progeny virus was very low. In mutant-infected HeLa cells there was a premature cessation of both cellular and viral protein synthesis followed by a premature halt of viral RNA synthesis. This nonspecific translational inhibition was distinguishable from wild-type-mediated inhibition and did not appear to be part of an interferon or heat shock response. Because the mutant is recessive, our results imply that (at least in HeLa cells) wild-type poliovirus not only actively inhibits translation of cellular mRNAs, but also avoids early inhibition of its own protein synthesis. Cleavage of the cap-binding complex protein P220, which has been associated with the selective inhibition of capped mRNA translation, did not occur in mutant-infected cells. This result supports the hypothesis that cleavage of P220 plays an important role in normal poliovirus-mediated translational inhibition.
Direct observation of kinetic traps associated with structural transformations leading to multiple pathways of S-layer assembly (2012)

The concept of a folding funnel with kinetic traps describes folding of individual proteins. Using in situ Atomic Force Microscopy to investigate S-layer assembly on mica, we show this concept is equally valid during self-assembly of proteins into extended matrices. We find the S-layer-on-mica system possesses a kinetic trap associated with conformational differences between a long-lived transient state and the final stable state. Both ordered tetrameric states emerge from clusters of the monomer phase, however, they then track along two different pathways. One leads directly to the final low-energy state and the other to the kinetic trap. Over time, the trapped state transforms into the stable state. By analyzing the time and temperature dependencies of formation and transformation we find that the energy barriers to formation of the two states differ by only 0.7 kT, but once the high-energy state forms, the barrier to transformation to the low-energy state is 25 kT. Thus the transient state exhibits the characteristics of a kinetic trap in a folding funnel.
Speech Analysis-Synthesis System Based on Homomorphic Filtering (1969)

A digital speech analysis-synthesis system based on a recently proposed approach to the deconvolution of speech [A. V. Oppenheim and R. W. Schafer, Homomorphic Analysis of Speech, Conference on Speech Communication and Processing (1967)] will be discussed. The analyzer is based on a computation of the cepstrum considered as the inverse Fourier transform of the log magnitude of the Fourier transform. The transmitted parameters represent pitch and voiced-unvoiced information as measured from the cepstrum, and the low-time portion of the cepstrum representing an approximation to the cepstrum of the vocal-tract impulse response. In the synthesis, the low-time cepstral information is transformed to an impulse response function which is then convolved with a train of impulses during voiced portions or a noise waveform during unvoiced portions to reconstruct the speech. Since no phase information is retained in the analysis, phase must be regenerated during synthesis. Either a zero-phase or minimum-phase characteristic can be obtained by simple weighting of the cepstrum before transformation [Lincoln Lab. operated with support from the U. S. Air Force.]
Analysis of platelet aggregation disorders based on flow cytometric analysis of membrane glycoprotein IIb-IIIa with conformation-specific monoclonal antibodies (1990)

Normal primary platelet aggregation requires agonist-mediated activation of membrane GPIIb-IIIa, binding of fibrinogen to GPIIb-IIIa, and cellular events after ligand binding. PAC1 monoclonal antibody distinguishes between resting and activated states of GPIIb-IIIa, and other antibodies preferentially recognize GPIIb (PMI-1) or IIIa (anti-LIBS1) after the binding of fibrinogen or fibrinogen-mimetic peptides, such as GRGDSP. Using these antibodies and platelet flow cytometry, we studied two distinct persistent platelet aggregation abnormalities. Platelets from a thrombasthenic variant, which contained near-normal amounts of GPIIb-IIIa, failed to aggregate or bind PAC1 in response to agonists. In addition, GRGDSP, which binds to normal GPIIb-IIIa without prior cell activation, failed to increase the binding of PMI-1 or anti-LIBS1 to the thrombasthenic platelets, suggesting a primary defect in ligand binding. Chromatography of detergent-solubilized platelets on a KYGRGDS affinity column confirmed that the patient's GPIIb-IIIa lacked the fibrinogen binding site. In another patient with myelofibrosis and defective aggregation, PAC1 failed to bind to adenosine diphosphate-stimulated platelets, but did bind when protein kinase C was directly activated with phorbol myristate acetate. Furthermore, the binding of PMI-1 and anti-LIBS1 increased in response to GRGDSP, confirming a defect in agonist-mediated fibrinogen receptor activation rather than in fibrinogen binding or events distal to binding. These studies indicate that this immunochemical approach is useful in classification of clinical abnormalities of platelet aggregation as defects in either (a) fibrinogen receptor activation, (b) fibrinogen binding, or (c) postoccupancy events.
Microbial Dynamics and In Vitro Degradation of Plant Secondary Metabolites in Hanwoo Steer Rumen Fluids (2021)

Plant secondary metabolite (PSM) degradations and feed breakdown into small particles may occur primarily in the rumen. It is possible to predict the rate and extent of feed disappearance in the rumen during incubation by different in vitro techniques, which differ based on the PSM structures, including phenolics, and flavonoids. However, PSM degradation and conversion efficiency in the rumen remains unclear. This study’s objective was to evaluate the in vitro degradation of a group of PSMs in the rumen fluid, collected from Hanwoo steer samples. PSMs including rutin, vitexin, myricetin, p-coumaric acid, ferulic acid, caffeic acid, quercetin, luteolin, propyl gallate, and kaempferol were used in their pure forms at 1mg/250 mL in a rumen fluid buffer system. The mixture of selected PSMs and buffer was incubated at 39 °C for 12–72 h, and samples were collected every 12 h and analyzed by a high-performance liquid chromatography-diode array detector (HPLC-DAD) to determine the biotransformation of the polyphenolics. The results revealed that the luteolin, ferulic acid, caffeic acid, coumaric acid, rutin, myricetin, vitexin, kaempferol, and quercetin were decreased after 12 h of incubation in the rumen fluid (p ≤ 0.05) and were more than 70% decreased at 72 h. In contrast, the propyl gallate concentrations were not significantly changed after 24 h of incubation in rumen fluid compared to other metabolites. Finally, microbial dynamics study showed that the Firmicutes, Bacterodetes, Actinobacteria, and Syngergistetes were the dominant phyla found in rumen fluids. The data suggest that most polyphenolic compounds may degrade or reform new complex structures in the rumen.