gebhart/patrepeval huggingface dataset:
OR09-6 Selective and Durable Suppression of Aldosterone Production in Non-Human Primates by a Novel Aldosterone Synthase Inhibitor (2019)

Primary aldosteronism (PA) is a common form of secondary hypertension driven by the autonomous production of aldosterone. Often described as low-renin hypertension, PA is a major public health concern given its prevalence and associated cardiovascular and renal pathology. Compared to patients with essential hypertension, patients with PA are at greater risk for stroke, coronary artery disease, atrial fibrillation, and heart failure. Aldosterone excess is also linked to vascular inflammation, fibrosis and oxidative stress. Aldosterone is produced in the adrenal glands by the enzyme CYP11B2 (aldosterone synthase). CYP11B2 belongs to the cytochrome P450 family of enzymes that also control cortisol (CYP11B1) and sex steroid synthesis (e.g. CYP17, CYP19). Thus, to safely suppress aldosterone synthesis in states of excess, a selective CYP11B2 inhibitor is required. SE-6440 is a novel CYP11B2 inhibitor; it is >200-fold selective over the closely related CYP11B1 enzyme as well as related adrenal and liver cytochrome P450 enzymes. Herein we describe the pharmacology of SE-6440 in non-human primate models of steroidogenesis using two different physiological inducers of aldosterone synthesis (Angiotensin II and ACTH). In monkeys, an i.v. bolus of Angiotensin II stimulates aldosterone synthesis and transiently elevates plasma aldosterone levels. Single oral doses of SE-6440 at 1 and 0.2 mg/kg suppressed aldosterone production in a dose-related manner to 3% and 26% that of vehicle-treated animals, respectively, without effect on cortisol synthesis. To determine if this selective inhibitory effect on aldosterone was durable, we dosed monkeys for 14-days with SE-6440 at 0.6 and 0.12 mg/kg orally once daily. Prior to SE-6440 treatment, animals received an i.v. bolus of ACTH to stimulate adrenal steroidogenesis. This ACTH stimulation test mimics that used clinically to diagnose adrenal insufficiency. Following ACTH administration, plasma aldosterone and cortisol pathway steroids were then measured for 8 hours. Each animal was used as its own control when ACTH was similarly administered on day 7 and day 14 of treatment with SE-6440. SE-6440 reduced plasma aldosterone levels, relative to pre-treatment levels, in a dose-related manner. The 0.6 mg/kg dose significantly inhibited aldosterone synthesis and yielded plasma aldosterone levels 13% and 15% that of control on days 7 and 14, respectively, while the 0.12 mg/kg daily dose reduced plasma aldosterone levels to 46% and 49% that of control on days 7 and 14, respectively. In both dose groups, there was no inhibition of CYP11B1 enzyme activity, based on the plasma cortisol, deoxycortisol, and DOC concentrations. These data demonstrate that, regardless of the stimulus, SE-6440 selectively inhibits aldosterone formation without affecting cortisol synthesis and that this inhibition is durable when administered orally once daily for 14 days.
Reply (1991)

Maguen, Ezra M.D.; Martinez, Marvin B.Sc.; Grundfest, Warren M.D.; Papaionnaou, Thanassis M.Sc.; Berlin, Michael M.D.; Nesburn, Anthony B. M.D.
Deep learning-based prediction of kinetic parameters from myocardial perfusion MRI (2019)

The quantification of myocardial perfusion MRI has the potential to provide a fast, automated and user-independent assessment of myocardial ischaemia. However, due to the relatively high noise level and low temporal resolution of the acquired data and the complexity of the tracer-kinetic models, the model fitting can yield unreliable parameter estimates. A solution to this problem is the use of Bayesian inference which can incorporate prior knowledge and improve the reliability of the parameter estimation. This, however, uses Markov chain Monte Carlo sampling to approximate the posterior distribution of the kinetic parameters which is extremely time intensive. This work proposes training convolutional networks to directly predict the kinetic parameters from the signal-intensity curves that are trained using estimates obtained from the Bayesian inference. This allows fast estimation of the kinetic parameters with a similar performance to the Bayesian inference.
Mild and Efficient Preparation of Block and Gradient Copolymers by Methanesulfonic Acid Catalyzed Ring-Opening Polymerization of Caprolactone and Trimethylene Carbonate (2013)

Polycaprolactone/polytrimethylene carbonate copolymers of different microstructures have been prepared in toluene solution under mild conditions by controlled ring-opening polymerization of ε-caprolactone and trimethylene carbonate with methanesulfonic acid as catalyst. Sequential addition of the monomers led to the formation of well-defined di- and tri-block copolymers, demonstrating the ability of the catalytic system to cross-propagate. Simultaneous copolymerization yielded gradient copolymers as a result of the different copolymerization reactivity ratios and absence of undesirable redistribution reactions. DSC analyses showed a noticeable impact of the copolymer microstructure on the thermal properties.
Two-Photon Photocurrent in InGaN/GaN Nanowire Intermediate Band Solar\n Cells (2020)

Intermediate band solar cells hold the promise of ultrahigh power conversion\nefficiencies using a single semiconductor junction. Many current\nimplementations use materials with bandgaps too small to achieve maximum\nefficiency or use cost-prohibitive substrates. Here we demonstrate a material\nsystem for intermediate band solar cells using InGaN/GaN\nquantum-dot-in-nanowire heterostructures grown directly on silicon to provide a\nlower cost, large-bandgap intermediate band solar cell platform. We demonstrate\nsequential two-photon current generation with sub-bandgap photons, the hallmark\nof intermediate band solar cell operation, through vertically stacked quantum\ndots in the nanowires. Near-infrared light biasing with an 850 nm laser\nintensity up to 200 W/cm2 increases the photocurrent above and below the\nbandgap by up to 19% at 78 K, and 44% at room temperature. The nanostructured\nIII-nitride strategy provides a route towards realistic room temperature\nintermediate band solar cells while leveraging the cost benefits of silicon\nsubstrates.\n
Critical role for intracellular calcium in tight junction biogenesis (1994)

Using the Madin Darby canine kidney (MDCK) cell "calcium switch," we have previously demonstrated that, as MDCK cells establish contact and ultimately form tight junctions, there are marked global and localized changes in intracellular calcium at the sites of cell-cell contact (Nigam et al., 1992, Proc. Natl. Acad. Sci. USA, 89:6162-6166). We have now examined whether intracellular Ca++ is critical to the biogenesis of tight junctions by chelating this ion and monitoring the formation of junctions by electrical, immunocytochemical, and biochemical criteria. Intracellular Ca++ was chelated with the cell-permeant chelators, dimethyl-BAPTA-AM and BAPTA-AM. By digital imaging of fura-2 loaded cells, it was demonstrated that both agents efficiently chelated Ca++ during the "switch" in a dose-dependent manner which paralleled their respective in vitro affinities for Ca++. Chelation of Ca++ during the switch markedly attenuated the development of transepithelial electrical resistance (TER), a measure of tight junction assembly. Immunofluorescent staining of the tight junctional protein, zonula occludens-1 (ZO-1), revealed that chelation of intracellular Ca++ retarded the movement of ZO-1 from intracellular sites to the plasma membrane during the switch. During the development of tight junctions, a fraction of ZO-1 redistributed from the Triton X-100 soluble to the Triton X-100 insoluble pool; chelation of Ca++ during the induction of cell-cell contact prevented this stabilization into the Triton X-100 insoluble fraction. Taken together, these data indicate an important role for intracellular Ca++ in tight junction biogenesis and suggest a specific role for calcium in the early sorting and possible cytoskeletal association of tight junction components.
Nonlinear amplification of circular dichroism activity upon cyclodimerization of a chiral saddle-shaped porphyrin (2002)

A cyclic dimer of chiral saddle-shaped porphyrin with p-xylylene linkers, upon interaction with mandelic acid, showed an enhanced circular dichroism activity, which was more than 7 times as large as that of a monomeric reference.
Palmitoylethanolamide Effects on Intraocular Pressure After Nd:YAG Laser Iridotomy: An Experimental Clinical Study (2011)

PEA can counteract the increase of IOP that occurs after iridotomy. It is likely that PEA controls the inflammatory process after iridotomy.
Influence of Longitudinal Reinforcement on One-Way Shear in Slabs and Wide Beams (2008)

Sectional shear models for slender reinforced concrete members developed by several research groups differ in the treatment of longitudinal reinforcement details when evaluating one-way shear capacity. Some models relate the shear capacity directly to the geometric reinforcement ratio while others consider the influence of reinforcement strain or stress. Further, only some models also consider the influence of member depth. The results from six new experimental tests on slender shear-critical members of varying depth, reinforcement ratio, and reinforcement strain at the time of failure are presented and compared with published data. The one-way shear stress at failure was accurately predicted using a recent modified compression field theory based capacity model that incorporates a “size effect” factor related to the member depth, and a “strain effect” factor related to the longitudinal reinforcement demands. Design implications for shear associated with the flexural reinforcement design strength are identified.
Directional etch of magnetic and noble metals. I. Role of surface oxidation states (2017)

An organic chemical etch process based on tailoring the surface oxidation state was found to be effective in realizing directional etch of magnetic and noble metals for their integration and application in magnetoresistive random access memory devices. Using Pt, a noble metal, as a test case, plasma treatments with sulfur- and oxygen-based chemistries were able to oxidize Pt0+ to Pt2+ and Pt4+, which can be effectively removed by selected organic chemistries. The most effective control of the surface oxidation states of Pt was achieved with an O2 plasma, which was then applied with similar effectiveness to other transition and noble metals. By quantifying the reaction rate, the oxidation of transition metals (Fe and Co) was shown to follow an inverse log rate law, while that of noble metals (Pd and Pt) follows a parabolic rate law. This work highlights the importance of the surface oxidation states of magnetic and noble metals in enabling directional etch by organic chemistry.
A multi-ancestry genome-wide study incorporating gene–smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure (2019)

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
SERUM COBALT AND CHROMIUM LEVELS AFTER HIP RESURFACING WITH THE CORMET 2000: EFFECTS OF GENDER AND FEMORAL HEAD SIZE (2009)

Metal-on-metal (MOM) hip resurfacing devices are known to release metal ions locally and into the systemic circulation. Previous studies suggest that larger prosthetic head size will correlate to reduced wear properties and may result in lower systemic release of metal ions. This project assessed the effect of femoral head size on serum cobalt (Co) and chromium (Cr) levels in subjects after unilateral hip resurfacing with the Cormet 2000 prosthesis. We prospectively collected patient characteristics, outcome, and serum samples from device implanted subjects at six months, one, two, and three years following surgery. Serum Co/Cr levels were determined using high-resolution inductively coupled plasma mass spectrometry. Students t-test was used to compare ion levels in two groups based on femoral head size. Thirty-five subjects (twenty male) were followed. Co/Cr levels were increased at all time points when compared to control levels. A significant negative correlation was observed between Co and Cr levels and femoral head size. Co/Cr levels in subjects with larger femoral heads were significantly lower when compared to those implanted with smaller heads (Co, −35.8%; Cr, −33.0%). This correlated with significantly higher Co/Cr levels in females versus males, with females receiving significantly smaller heads on average. Elevated serum Co/Cr levels were observed at all time points following implantation and in females and in subjects with femoral heads.
Surface Modification of Selective Laser Melted Structures Using Self-Assembled Monolayers for Biomedical Applications (2012)

The potential of the selective laser melting (SLM) process to fabricate biomedical implants has been studied widely in recent years due to its ability to build complex and customised structures. Although SLM is capable of building almost any desired geometry, the surface properties of the produced parts are not controlled by the process and may not be suitable for many applications. Hence in this study, the coating of self-assembled monolayers (SAMs) onto SLM fabricated Ti6Al4V structures to modify surface chemistry has been studied. 16-phosphanohexadecanoic acid monolayers were used to modify SLM as-fabricated (SLM-AF) and mechanically polished (SLM-MP) surfaces. X-ray photoelectron spectroscopy (XPS) and static water contact angle measurements confirmed the formation of monolayers on these surfaces. The covalently bonded monolayers were found to be stable for up to six weeks immersion in Tris-HCl buffer solution. Stability of monolayers on SLM-AF and SLM-MP was not significantly different. This study demonstrates the possibility of forming stable phosphonic acid monolayers on SLM fabricated Ti6Al4V surfaces.
Orthoretroviral-like prototype foamy virus gag-pol expression is compatible with viral replication (2011)

Non-particle associated PFV Pol appears to be naturally released from infected cells by a yet unknown mechanism. The absence of particle-associated Pol precursor suggests its rapid processing upon particle incorporation. Analysis of different PFV Gag-Pol fusion constructs demonstrates that orthoretroviral-like Pol expression is compatible with FV replication in principal as long as fusion protein processing is possible. Furthermore, unlike orthoretroviruses, PFV particle release and infectivity tolerate larger differences in relative cellular Gag/Pol levels.
Enantioselective Organocatalytic Aminomethylation of Aldehydes (2006)

A highly enantioselective amino­methylation of aldehydes is presented. The Mannich addition of aldehydes to a formaldehyde iminium ion is catalyzed by Jørgensen-Hayashi’s catalyst A and provides α-substituted β -amino aldehydes with moderate to good yields and excellent enantioselectivities. To avoid racemization, Mannich products were immediately reduced to the corresponding β -substituted γ-amino alcohols. Ionic interactions occurring during the transition state of the reaction are proposed to influence the stereo­chemical outcome and the use of 1 M LiCl leads to a moderate enantioselectivity enhancement. The β -substituted γ-amino alcohols generated via Mannich reaction/reduction could be successfully converted into β2-amino acids on a several-gram scale through a short and simple pathway.
Sensor applications at Kennedy Space Center (KSC) (2003)

Transducers used at KSC, in support of processing and launch of flight vehicles and payloads, are designed and tested to meet specific program requirements. Any equipment, transducer or support instrumentation in direct contact or in support to flight vehicle operations is considered ground support equipment (GSE) and required to meet strict program requirements (i.e. Space Shuttle Program, Space Station Program, Evolved Expendable Launch Vehicles, etc.) Transducers used in KSC applications are based on commercial-off-the-shelf transducers and sensor. In order to fully meet KSC requirements, these transducers evolve from standard COTS to modified COTS. The Transducer and Data Acquisition Group of the Instrumentation Branch at Kennedy Space Center is responsible for providing the technical expertise as well as qualification-testing capability to transform these COTS transducers in modified COTS suitable for use around flight hardware.
Insulin action in pancreatic acini from streptozotocin-treated rats. II. Binding of 125I-insulin to receptors (1981)

The binding of 125I-insulin to its receptors was investigated with isolated pancreatic acini obtained from diabetic rats under incubation conditions identical to those used to study the effects of insulin on acinar cell protein synthesis. Binding was specific, time dependent, reversible, and linearly related to the acinar protein content. Degradation of insulin after 30 min of incubation was less than 10% of the total hormone present in the incubation medium. 125I-insulin dissociated from acini with a one-half time of 9 min. Unlabeled insulin at 83.5 nM accelerated the rate of dissociation of labeled insulin. 125I-insulin binding to acini was competitively inhibited by insulin and its analogues in proportion to their biological potencies. Scatchard analysis revealed a major class of insulin-binding sites with a Kd of 1.6 nM; maximal stimulation of protein synthesis was observed when > 90% of these high-affinity receptors were occupied. These studies indicate, therefore, that insulin binding to receptors on pancreatic acini can be correlated with subsequent regulation of biological functions.
ChemInform Abstract: A STUDY OF THE SYNTHESIS OF OPTICALLY ACTIVE AMINES FROM PROCHIRAL N‐PHOSPHINYLIMINES (1982)

Abstract Die aus den Oximen (I) mit Diphenylchlorphosphan (II) leicht zugänglichen Alkylidendiphenylphosphinimide (III) lassen sich mit LiAlH 4 in Gegenwart von optisch aktivem Chinin zu den optisch aktiven N‐Alkyldiphenylphosphinamiden (IV) reduzieren, deren saure Hydrolyse die optisch aktiven Amine (V) zugänglich macht.
Atom arrangement strategy for designing a turn-on1H magnetic resonance probe: a dual activatable probe for multimodal detection of hypochlorite (2011)

The first dual activatable hypochlorite ((-)OCl)-sensing probe was developed, based on a new proof-of-concept design involving signal-activatable (1)H chemical probes using the triple-resonance NMR technique. The probe enabled fluorescence-(1)H MR dual turn-on detection of (-)OCl in solution and in crude tissue extracts.
Altbestand.digital – neue Formen der Kooperation zwischen öffentlichen und wissenschaftlichen Bibliotheken in Sachsen (2022)

Die AltbestÃ¤nde Ãffentlicher Bibliotheken in Sachsen erfahren nicht zuletzt durch Provenienz- bzw.Â NS-Raubgutforschung und Digitalisierung (neue) erhÃ¶hte Aufmerksamkeit. Sind die AltbestÃ¤nde der groÃen Stadtbibliotheken bekannt, stellt sich die Katalogisierungssituation an den kleineren Bibliotheken meist anders dar. Ãber die StÃ¤dte und Gemeinden hinaus ist nur selten bekannt, welche AltbestÃ¤nde vorhanden sind, in welcher GrÃ¶Ãe, welchen Inhalts und welcher Provenienzen. Dies zu erforschen ist jedoch eine der Aufgaben der Koordinierungsstelle, die im Oktober 2021 an der SÃ¤chsischen Landesfachstelle fÃ¼r Bibliotheken geschaffen wurde. Mit der im Januar 2022 als Stabsstelle an die SLUB Ã¼berfÃ¼hrten Landesfachstelle besitzt die SLUB Kompetenzen in Provenienzforschung sowohl im wissenschaftlichen als auch Ã¶ffentlichen Bibliotheksbereich. Im Beitrag wird dargestellt, wie bisher in diesem Bereich Ãffentliche und Wissenschaftliche Bibliotheken kooperieren und welche Perspektiven bestehen. Mit dem seit 2015 laufenden und ebenfalls an der SLUB angesiedelten Landesdigitalisierungsprogramm fÃ¼r Wissenschaft und Kultur, in dem bereits einige grÃ¶Ãere Ãffentliche Bibliotheken Teile ihrer AltbestÃ¤nde digitalisiert haben, steht ein Instrument fÃ¼r die Digitalisierung, PrÃ¤sentation und nachhaltige Langzeitarchivierung in einem integrierten Workflow zur VerfÃ¼gung.Â ZukÃ¼nftig kÃ¶nnen in gemeinsamen Projekten mit der Landesfachstelle historische BestÃ¤nde und Provenienzkennzeichen aus sÃ¤chsischen Bibliotheken in digitaler Form zugÃ¤nglich gemacht werden. Auf diese Weise wird die Zusammenarbeit zwischen WBs und ÃBs in Sachsen wie kaum zuvor intensiviert, die in gemeinsamer Projektplanung, Beurteilung des Bestands (auch unter Aspekten der Provenienzforschung), DurchfÃ¼hrung der Digitalisierung, PrÃ¤sentation und Archivierung der Dateien besteht. Bereits bei der Projektplanung wird darauf geachtet, auch bÃ¼rgerwissenschaftlich relevante BestÃ¤nde zu berÃ¼cksichtigen, mit denen im Sinne der Teilhabe in gemeinsamen Vorhaben zwischen ÃB und BÃ¼rgergesellschaft gearbeitet wird.
PET performance measurements using the NEMA NU 2-2001 standard. (2002)

The changes from the NU 2-1994 standard to the NU 2-2001 standard strive toward establishing relevance with clinical studies. The tests in the updated standard also are, in general, simpler and less time-consuming to perform than those in the NU 2-1994 standard.
Energy recovery and efficiency optimisation in a wood cutting machines (2013)

Wood cutting machine process is characterized by multi axes high acceleration and deceleration phases and requires relevant electric energy amount to operate. Moreover not all the energy involved in the process is really used as a part of it is usually wasted and lost during movement phases. In particular the electrical power generated during the deceleration phases is significant and it is usually transformed into heat using braking resistance banks. As a consequence conditioning systems are usually adopted to remove the heat produced during the wood cutting process and to avoid electrical rack failure due to over-temperature operations. These solutions imply a significant energy waste which decreases the efficiency of all the wood cutting process. The present paper proposes an energy recovery system which can be adopted and installed also on existing machines and which allows to store the amount of energy produced during deceleration phases and to use this energy during the acceleration phases of the machine axis. A prototype has been realized and tested.