gebhart/patrepeval huggingface dataset:
Pathogenesis of Fecal Incontinence in Diabetes Mellitus (1982)

We studied 16 patients with diabetes and fecal incontinence. The onset of incontinence coincided with the onset of chronic diarrhea in most patients. Episodes of incontinence occurred when stools were frequent and loose; however, 24-hour stool weights were usually within normal limits. All patients had evidence of autonomic neuropathy, and one third had steatorrhea. Incontinent diabetics had a lower mean basal anal-sphincter pressure than 35 normal subjects (63 +/- 4 vs. 37 +/- 4 mm Hg; P less than 0.001), reflecting abnormal internal-anal-sphincter function. The increment in sphincter pressure with voluntary contraction (external-sphincter function) was not significantly different from normal. Incontinent diabetics also had impaired continence for a solid sphere and for rectally infused saline. In contrast, 14 diabetics without diarrhea or incontinence had normal sphincter pressures and normal results on tests of continence, even though 79 per cent had evidence of autonomic neuropathy and nearly half had steatorrhea. We conclude that incontinence in diabetic patients is related to abnormal internal-anal-sphincter function, and that as a group, diabetics without diarrhea do not have latent defects in continence.
Joint impact of random variations and RTN on dynamic writeability in 28nm bulk and FDSOI SRAM (2014)

Improving SRAM minimum operating voltage (V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">min</inf> ) in scaled process nodes requires characterization of different failure mechanisms. Persistent errors caused by random variations and intermittent errors caused by random telegraph noise (RTN) both contribute to bitcell failure. Random V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</inf> shift was measured for 32,000 in-situ SRAM cells in both 28nm bulk and FDSOI processes due to both random variations and RTN, and dynamic writeability was measured by two different write modes that accentuate different RTN behaviour. Measured distribution parameters of both random variation and RTN were used to calibrate an accelerated Monte Carlo simulation that predicts a V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">min</inf> difference due to RTN. Measurements show that while FDSOI technology reduces random variation by approximately 27% compared to bulk, similar RTN amplitudes slightly increase bitcell susceptibility to failures caused by RTN.
Mechanical properties and upsettability of alumina/alminum powder composites. (1990)

Alumina/aluminum composites were fabricated by sintering or extruding subsequently mixed powder of a pure aluminum and an alumina. Some mechanical properties, a critical reduction in height in upsetting and changes in the properties after upsetting were investigated for the composites. Although a pure aluminum fabricated from the powder had higher strength than a cast aluminum because of so-called SAP effect, a good wear resistance was obtained only in a composite specimen containing alumina particles.
Abstract A014: Cytokines surge in the blood years prior to a cancer diagnosis in elderly individuals (2023)

Abstract This abstract is being presented as a short talk in the scientific program. A full abstract is available in the Short Talks from Proffered Abstracts section (PR002) of the Conference Proceedings. Citation Format: Guangbo Chen, Hong Zheng, Yael Rosenberg-Hasson, Saron Araya, Cindy Padilla, Kavita Sarin, Cornelia L. Dekker, Philip Grant, Holden T. Maecker, David Furman, Shai Shen-Orr, Purvesh Khatri, Mark M. Davis. Cytokines surge in the blood years prior to a cancer diagnosis in elderly individuals [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A014.
Induced sputum to detect lung pathogens in young children with cystic fibrosis (2016)

Induced sputum is not highly sensitive or specific as routine surveillance for detection of lower airway pathogens in young children with cystic fibrosis. Pediatr Pulmonol. 2017;52:182-189. © 2016 Wiley Periodicals, Inc.
Spinal cord stimulation for chronic intractable pain (1995)

The “gate theory” of pain transmission in the dorsal horn of the spinal cord, published in 1965, provided the foundation for the use of electrical stimulation for pain relief (57). The feasibility of chronic neural stimulation was greatly increased when the miniaturized highly reliable solid-state electronic technology developed for cardiac pacemakers was transferred to implantable neural stimulators.
Transcatheter stent-valve implantation in a stenotic pulmonary conduit via a sub-xyphoidian access (2009)

Patients who develop a severe stenosis in biological pulmonary conduits previously implanted for pulmonary outflow trunk reconstructions are treated either by surgical re-replacement, or by transcatheter stent-valve implantation through a femoral vein access. A catheter-based sub-xyphoidian access through the right ventricle for stent-valve positioning in a pulmonary conduit has rarely been proposed. We describe the case of a 20-year-old man who underwent a pulmonary trunk reconstruction for a congenital pulmonary valve dysplasia and a few years later developed a stenosis in the pulmonary conduit. He was successfully treated with a 23 mm Edwards Sapien stent-valve implantation in pulmonary position, through an unusual right ventricular, sub-xyphoidian access and without contrast medium injections and pleura opening.
A novel glucagon‐like peptide 1/glucagon receptor dual agonist improves steatohepatitis and liver regeneration in mice (2016)

Dual-acting glucagon-like peptide-1/glucagon receptor agonists such as G49 represent a novel therapeutic approach for patients with NASH and particularly those requiring PH. (Hepatology 2017;65:950-968).
Preparation and Magnetic Properties of Oxide-Coated Monodispersive Co Cluster Assembly (1999)

Oxide-coated monodispersive Co cluster assemblies with the mean cluster size of 6 and 13 nm have been prepared by a plasma-gas-condensation type cluster beam deposition apparatus. The magnetic properties of the samples prepared without and with introducing oxygen gas into the deposition chamber are compared. The exchange anisotropy induced by interfacial exchange coupling between the ferromagnetic Co core and the antiferromagnetic cobalt oxide shell has been studied by measuring the hysteresis loop shift of the field-cooled samples and the low field thermomagnetic curve.
The Pierre Auger Observatory V: Enhancements (2011)

Ongoing and planned enhancements of the Pierre Auger Observatory
Crosslinking and decomposition reactions of epoxide functionalized polynorbornene. Part I. FTIR and thermogravimetric analysis (2003)

Abstract The miniaturization of microelectronic devices has created a demand for new low‐dielectric‐constant materials to be used as insulating layers between metal interconnects. In this study, a functionalized polynorbornene consisting of a copolymer of decyl norbornene and epoxide norbornene has been investigated as a low‐temperature curing dielectric. Polynorbornenes possess properties that are attractive for microelectronics packaging; however, films of these polymers must be crosslinked in order to obtain the solvent resistance and low solvent swelling necessary for multilayer applications. Crosslinking of these materials was achieved by acid‐catalyzed cationic crosslinking of epoxide side groups. The reactions that occurred during higher temperature curing of epoxy functionalized norbornene films were studied using Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis. Epoxide crosslinking and epoxide decomposition reactions were identified and studied as a function of temperature and time. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 568–577, 2003
Preparation and use of benzhydrylamine polymers in peptide synthesis. II. Synthesis of thyrotropin releasing hormone, thyrocalcitonin 26-32, and eledoisin (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation and use of benzhydrylamine polymers in peptide synthesis. II. Synthesis of thyrotropin releasing hormone, thyrocalcitonin 26-32, and eledoisinPietro G. Pietta, P. F. Cavallo, Kiyohisa Takahashi, and Garland R. MarshallCite this: J. Org. Chem. 1974, 39, 1, 44–48Publication Date (Print):January 1, 1974Publication History Published online1 May 2002Published inissue 1 January 1974https://pubs.acs.org/doi/10.1021/jo00915a008https://doi.org/10.1021/jo00915a008research-articleACS PublicationsRequest reuse permissionsArticle Views229Altmetric-Citations74LEARN 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 Other access optionsGet e-Alertsclose Get e-Alerts
Assessment of Cryosurgical Device Performance Using a 3D Tissue-Engineered Cancer Model (2017)

As the clinical use of cryoablation for the treatment of cancer has increased, so too has the need for knowledge on the dynamic environment within the frozen mass created by a cryoprobe. While a number of factors exist, an understanding of the iceball size, critical isotherm distribution/penetration, and the resultant lethal zone created by a cryoprobe are critical for clinical application. To this end, cryoprobe performance is typically characterized based on the iceball size and temperature penetration in phantom gel models. Although informative, these models do not provide information as to the impact of heat input from surrounding tissue nor give any information on the ablative zone created. As such, we evaluated the use of a tissue-engineered tumor model (TEM) to assess cryoprobe performance including iceball size, real-time thermal profile distribution, and resultant ablative zone. Studies were conducted using an Endocare V-probe cryoprobe, with a 10/5/10 double freeze-thaw protocol using prostate and renal cancer TEMs. The data demonstrate the generation of a 33- to 38-cm3 frozen mass with the V-Probe cryoprobe following the double freeze of which ∼12.7 and 6.5 cm3 was at or below -20°C and -40°C, respectively. Analysis of ablation zone using fluorescence microscopy 24 hours postthaw demonstrated that the internal ∼40% of the frozen mass was completely ablated, whereas in the periphery of the iceball (outer 1 cm region), a gradient of partial to minimal destruction was observed. These findings correlated well with clinical reports on renal and prostate cancer cryoablation. Overall, this study demonstrates that TEMs provide an effective model for a more complete characterization of cryoablation device performance. The data demonstrate that while the overall iceball size generated in the TEM was consistent with published reports from phantom models, the integration of an external heat load, circulation, and cellular components more closely reflect an <i>in vivo</i> setting and the impact of penetration of the critical (-20°C and -40°C) isotherms into the tissue. This is important as it is well appreciated in clinical practice that the heat load of a tissue, cryoprobe proximity to vasculature, and so on, can impact outcome. The TEM model provides a means of characterizing the impact on ablative dose delivery allowing for a better understanding of probe performance and potential impact on ablative outcome.
Cell bioenergetics in Leghorn male hepatoma cells and immortalized chicken liver cells in response to 4-hydroxy 2-nonenal-induced oxidative stress (2014)

The major objectives of this study were to compare cell bioenergetics in 2 avian liver cell lines under control conditions and in response to oxidative stress imposed by 4-hydroxy 2-nonenal (4-HNE). Cells in this study were from a chemically immortalized Leghorn male hepatoma (LMH) cell line and a spontaneously immortalized chicken liver (CELi) cell line. Oxygen consumption rate (OCR) was monitored in specialized microtiter plates using an XF24 Flux Analyzer (Seahorse Bioscience, Billerica, MA). Cell bioenergetics was assessed by sequential additions of oligomycin, carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and antimycin-A that enables the determination of a) OCR linked to adenosine triphosphate (ATP) synthase activity, b) mitochondrial oxygen reserve capacity, c) proton leak, and d) nonmitochondrial cytochrome c oxidase activity. Under control (unchallenged) conditions, LMH cells exhibited higher basal OCR and higher OCR attributed to each of the bioenergetic components listed above compared with CELi cells. When expressed as a percentage of maximal OCR (following uncoupling with FCCP), LMH cells exhibited higher OCR due to ATP synthase and proton leak activity, but lower mitochondrial oxygen reserve capacity compared with CELi cells; there were no differences in OCR associated with nonmitochondrial cytochrome c oxidase activity. Whereas the LMH cells exhibited robust ATP synthase activity up to 50 μM 4-HNE, CELi cells exhibited a progressive decline in ATP synthase activity with 10, 20, and 30 μM 4-HNE. The CELi cells exhibited higher mitochondrial oxygen reserve capacity compared with LMH cells with 0 and 20 μM 4-HNE but not with 30 μM 4-HNE. Both cell lines exhibited inducible proton leak in response to increasing levels of 4-HNE that was evident with 30 μM 4-HNE for CELi cells and with 40 and 50 μM 4-HNE in LMH cells. The results of these studies demonstrate fundamental differences in cell bioenergetics in 2 avian liver-derived cell lines under control conditions and in response to oxidative challenge due to 4-HNE.
Optical Equalization of 42.7-Gbaud Band-Limited NRZ-DQPSK Signals for High-Spectral-Efficiency Transmission (2007)

We demonstrate the use of an optical equalizer to allow a 42.7-Gbaud (85.4-Gb/s) NRZ-DQPSK signal to tolerate the narrow optical filtering required in high-spectral-efficiency systems. The equalizer passbands are repetitive, enabling equalization of multiple channels.
Supplementary Figures 1-6 from The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity (2023)

Supplementary Figures 1-6 from The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity
Inhibition of Hypoxia-Inducible Factor Prolyl Hydroxylase Domain Oxygen Sensors: Tricking the Body into Mounting Orchestrated Survival and Repair Responses (2013)

Hypoxia-inducible factor (HIF) is an oxygen-sensitive dimeric transcription factor that responds to pathophysiologically low O2 tensions via up-regulation, which leads to an orchestrated biological response to hypoxia. The HIF prolyl hydroxylase domain (PHD) enzymes are non-heme, iron-containing dioxygenases requiring for activity both molecular oxygen and 2-oxoglutarate that, under normoxia, selectively hydroxylate proline residues of HIF, initiating proteosomal degradation of the latter. The dependence of HIF protein levels on the concentration of O2 present, mediated by the PHD enzymes, forms the basis for one of the most significant biological sensor systems of tissue oxygenation in response to ischemic and inflammatory events. Consequently, pharmacological inhibition of PHD enzymes, leading to stabilization of HIF, may be of considerable therapeutic potential in treating conditions of tissue stress and injury. This Perspective reviews the PHDs and small molecule drug discovery efforts. A critical view of this challenging field is offered, which addresses potential concerns and highlights exciting possibilities for the future.
Inhibition of Nucleoside Transport by New Analogues of 4-Nitrobenzylthioinosine:  Replacement of the Ribose Moiety by Substituted Benzyl Groups (2004)

4-Nitrobenzylthioinosine (NBTI, 1) is a well-known inhibitor for the nucleoside transport protein ENT1. However, its highly polar nature is unfavorable for oral absorption and/or penetration into the CNS. In the search for compounds with lower polarity than NBTI we replaced its ribose moiety by substituted benzyl groups. Halogen, hydroxyl, (trifluoro)methyl(-oxy), nitro, and amine functionalities were among the substituents at the benzyl group. In general, substitution of the benzyl group resulted in a lower affinity for ENT1. Only 2-hydroxyl substitution showed a higher affinity. Most likely this is the result of hydrogen bonding. Substitution at the 2-position of the benzyl group with aryl groups was also addressed. Compared to parent compound carrying a 2-phenylbenzyl group, all synthesized analogues gave higher affinities. Introduction of fluoro, trifluoromethyl, methoxy, and hydroxyl groups at the phenyl group clearly showed that addition to the 4-position was preferable. Despite the highly different character of a ribose and a benzyl group, Ki values in the low nanomolar range were obtained for the benzyl-substituted derivatives. Compound 35, LUF5919, and compound 60, LUF5929, displayed the highest affinity (Ki = 39 nM for both compounds), having a polar surface area of 101 A2 and 85 A2, respectively.
Chemokine receptors (version 2020.5) in the IUPHAR/BPS Guide to Pharmacology Database (2020)

Chemokine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Chemokine Receptors [431, 430, 32]) comprise a large subfamily of 7TM proteins that bind one or more chemokines, a large family of small cytokines typically possessing chemotactic activity for leukocytes. Additional hematopoietic and non-hematopoietic roles have been identified for many chemokines in the areas of embryonic development, immune cell proliferation, activation and death, viral infection, and as antibiotics, among others. Chemokine receptors can be divided by function into two main groups: G protein-coupled chemokine receptors, which mediate leukocyte trafficking, and "Atypical chemokine receptors", which may signal through non-G protein-coupled mechanisms and act as chemokine scavengers to downregulate inflammation or shape chemokine gradients [32].Chemokines in turn can be divided by structure into four subclasses by the number and arrangement of conserved cysteines. CC (also known as β-chemokines; n= 28), CXC (also known as α-chemokines; n= 17) and CX3C (n= 1) chemokines all have four conserved cysteines, with zero, one and three amino acids separating the first two cysteines respectively. C chemokines (n= 2) have only the second and fourth cysteines found in other chemokines. Chemokines can also be classified by function into homeostatic and inflammatory subgroups. Most chemokine receptors are able to bind multiple high-affinity chemokine ligands, but the ligands for a given receptor are almost always restricted to the same structural subclass. Most chemokines bind to more than one receptor subtype. Receptors for inflammatory chemokines are typically highly promiscuous with regard to ligand specificity, and may lack a selective endogenous ligand. G protein-coupled chemokine receptors are named acccording to the class of chemokines bound, whereas ACKR is the root acronym for atypical chemokine receptors [33]. There can be substantial cross-species differences in the sequences of both chemokines and chemokine receptors, and in the pharmacology and biology of chemokine receptors. Endogenous and microbial non-chemokine ligands have also been identified for chemokine receptors. Many chemokine receptors function as HIV co-receptors, but CCR5 is the only one demonstrated to play an essential role in HIV/AIDS pathogenesis. The tables include both standard chemokine receptor names [684] and aliases.
Mechanism of Inactivation of γ-Aminobutyric Acid Aminotransferase by (1S,3S)-3-Amino-4-difluoromethylene-1-cyclopentanoic Acid (CPP-115) (2015)

γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently, CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. This represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.
Organometallic catalysis in air and water: oxygen-enhanced, nickel-catalyzed polymerizations of isocyanides (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOrganometallic catalysis in air and water: oxygen-enhanced, nickel-catalyzed polymerizations of isocyanidesTimothy J. Deming and Bruce M. NovakCite this: Macromolecules 1991, 24, 1, 326–328Publication Date (Print):January 1, 1991Publication History Published online1 May 2002Published inissue 1 January 1991https://pubs.acs.org/doi/10.1021/ma00001a051https://doi.org/10.1021/ma00001a051research-articleACS PublicationsRequest reuse permissionsArticle Views382Altmetric-Citations38LEARN 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 Other access optionsGet e-Alertsclose Get e-Alerts