gebhart/patrepeval huggingface dataset:
A Positive Allosteric Modulator of the Serotonin 5-HT2CReceptor for Obesity (2017)

The 5-HT<sub>2C</sub>R agonist lorcaserin, clinically approved for the treatment of obesity, causes important side effects mainly related to subtype selectivity. In the search for 5-HT<sub>2C</sub>R allosteric modulators as safer antiobesity drugs, a chemical library from Vivia Biotech was screened using ExviTech platform. Structural modifications of identified hit VA240 in synthesized analogues 6-41 afforded compound 11 (N-[(1-benzyl-1H-indol-3-yl)methyl]pyridin-3-amine, VA012), which exhibited dose-dependent enhancement of serotonin efficacy, no significant off-target activities, and low binding competition with serotonin or other orthosteric ligands. PAM 11 was very active in feeding inhibition in rodents, an effect that was not related to the activation of 5-HT<sub>2A</sub>R. A combination of 11 with the SSRI sertraline increased the anorectic effect. Subchronic administration of 11 reduced food intake and body weight gain without causing CNS-related malaise. The behavior of compound 11 identified in this work supports the interest of a serotonin 5-HT<sub>2C</sub>R PAM as a promising therapeutic approach for obesity.
Antisense Oligonucleotide-Mediated Silencing of Mitochondrial Fusion and Fission Factors Modulates Mitochondrial Dynamics and Rescues Mitochondrial Dysfunction (2021)

Mitochondria are highly dynamic organelles that produce ATP and maintain metabolic, catabolic, and redox homeostasis. Mitochondria owe this dynamic nature to their constant fission and fusion-processes that are regulated, in part, by fusion factors (MFN1 and MFN2) and fission factors (DRP1, FIS1, MFF, MIEF1, MIEF2) located on the outer mitochondrial membrane. While mitochondrial fusion and fission are known to influence mitochondrial morphology and function, a key question is whether rebalancing mitochondrial morphology can ameliorate mitochondrial dysfunction in the context of mitochondrial pathology. In this study, we used antisense oligonucleotides (ASOs) to systematically evaluate the effects of fusion and fission factors <i>in vitro</i>. Free uptake by cells of fusion or fission factor ASOs caused robust decreases in target gene expression and altered a variety of mitochondrial parameters, including mitochondrial size and respiration, which were dose dependent. In <i>Mfn1</i> knockout mouse embryonic fibroblasts (MEFs) and MFN2-R94Q (Charcot-Marie-Tooth Type 2 Disease-associated mutation) MEFs, two cellular models of mitochondrial dysfunction, we found that ASO-mediated silencing of only <i>Drp1</i> restored mitochondrial morphology and enhanced mitochondrial respiration. Together, these data demonstrate <i>in vitro</i> proof-of-concept for rebalancing mitochondrial morphology to rescue function using ASOs and suggest that ASO-mediated modulation of mitochondrial dynamics may be a viable therapeutic approach to restore mitochondrial homeostasis in diseases driven by mitochondrial dysfunction.
Purification of Hepatitis A Virus from Human Feces (1978)

Hepatitis A virus was purified fecal specimens obtained from 2 patients with naturally acquired hepatitis A. The purification procedure involved differential centrifugation, organic solvent extraction, agarose gel filtration, ion-exchange chromatography, and isopycnic ultracentrifugation in cesium chloride. Using immune electron microscopy and discontinuous SDS-PAGE, this procedure was found to be effective in removing extraneous material from hepatitis A virus. There was significant recovery of virus as judged by immune electron microscopy and solid-phase radioimmunoassay. Using this protocol, it has been possible to obtain virus preparations of sufficient purity and high enough titer to enable biochemical studies to proceed.
Coronary artery disease in adults with tetralogy of Fallot (2019)

Based on a review of a selected cohort of 105 TOF patients, the prevalence of mild CAD and significant CAD was 19% and 15%, respectively. Significant CAD was an independent risk factor for mortality. There is need for more research to determine optimal noninvasive diagnostic strategies and optimal patient selections and methods for revascularization.
The Use of Chromium(III) to Supercharge Peptides by Protonation at Low Basicity Sites (2014)

The addition of chromium(III) nitrate to solutions of peptides with seven or more residues greatly increases the formation of doubly protonated peptides, [M + 2H](2+), by electrospray ionization. The test compound heptaalanine has only one highly basic site (the N-terminal amino group) and undergoes almost exclusive single protonation using standard solvents. When Cr(III) is added to the solution, abundant [M + 2H](2+) forms, which involves protonation of the peptide backbone or the C-terminus. Salts of Al(III), Mn(II), Fe(III), Fe(II), Cu(II), Zn (II), Rh(III), La(III), Ce(IV), and Eu(III) were also studied. Although several metal ions slightly enhance protonation, Cr(III) has by far the greatest ability to generate [M + 2H](2+). Cr(III) does not supercharge peptide methyl esters, which suggests that the mechanism involves interaction of Cr(III) with a carboxylic acid group. Other factors may include the high acidity of hexa-aquochromium(III) and the resistance of Cr(III) to reduction. Nitrate salts enhance protonation more than chloride salts and a molar ratio of 10:1 Cr(III):peptide produces the most intense [M + 2H](2+). Cr(III) also supercharges numerous other small peptides, including highly acidic species. For basic peptides, Cr(III) increases the charge state (2+ versus 1+) and causes the number of peptide molecules being protonated to double or triple. Chromium(III) does not supercharge the proteins cytochrome c and myoglobin. The ability of Cr(III) to enhance [M + 2H](2+) intensity may prove useful in tandem mass spectrometry because of the resulting overall increase in signal-to-noise ratio, the fact that [M + 2H](2+) generally dissociate more readily than [M + H](+), and the ability to produce [M + 2H](2+) precursors for electron-based dissociation techniques.
Novel green coloration of cotton fabric. Part II: Effect of different print paste formulations on the printability of bio-mordanted fabric with madder natural dye (2020)

Gelatin-tannic acid (bio-mordant) treated cotton fabric was printed with natural and synthetic thickeners. Madder natural dye was used with different thickeners include meypro gum, carboxymethyl cellulose, sodium alginate, or acrylate-based synthetic thickener. Different factors such as pH, steaming temperatures, time, auxiliaries (urea, salt, and binder) presence or absence in the print paste formulations were investigated. The data indicated good quality prints using natural thickeners and without auxiliaries compared with the synthetic one. The printed samples reveal very good to excellent fastness properties. Hence, the present process of printing cotton fabric with green print paste formulation and without auxiliaries may find wide application in textile coloration.
KRAS Mutations in Primary Colorectal Cancer Tumors and Related Metastases: A Potential Role in Prediction of Lung Metastasis (2009)

Our results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to metastasize to the lung.
Occult core hyperthermia complicating cardiogenic shock. (1989)

Cardiogenic shock severely limits tissue perfusion. Conventional therapy of cardiogenic shock is directed at increasing cardiac output; however, decreasing oxygen demand by recognition and control of core (central thoracic) hyperthermia is also helpful. Core hyperthermia complicating cardiogenic shock has been reported in adults but not in children. In the last year, we treated three children with cardiogenic shock in whom core temperature was much higher than rectal temperature. Without central temperature measurement, this occult core hyperthermia would not have been recognized or treated. Treatment of core hyperthermia combined with standard therapy (mechanical ventilation, inotropes, and vasodilators) resulted in long-term survival of all patients.
High-Energy Proton Radiation Damage of High-Purity Germanium Detectors (1978)

Motivated by their applicability to gamma-ray spectroscopy experiments in space, quantitative studies of radiation damage effects in high-purity germanium detectors due to high-energy charged particles have been initiated with the irradiation by 6 GeV/c protons of two 1.0 cm thick planar detectors maintained at 88°K. The threshold for resolution degradation and the annealing characteristics differ markedly from those previously observed for detectors irradiated by fast neutrons. Under proton bombardment, degradation in the energy resolution was found to begin below 7 × 107 protons/cm2, and increased proportionately in both detectors until the experiment was terminated at a total flux of 5.7 × 108 protons/cm2, equivalent to about a six year exposure to cosmic-ray protons in space. At the end of the irradiation, the FWHM resolution measured at 1332 keV stood at 8.5 and 13.6 keV, with both detectors of only marginal utility as a spectrometer due to the severe tailing caused by charge trapping. The two detectors displayed a significant difference in proton damage sensitivity, which is consistent with fast neutron damage effects. To ensure that detector variability did not influence the comparision of proton-and neutron-induced damage effects, one of the detectors had been used previously in a neutron damage experiment. The threshold for high-energy proton damage was found to be markedly lower, roughly 5 × 107 protons/cm2, compared to 3 × 109 neutrons/cm2 for fast neutrons. Annealing these detectors after proton damage was found to be much easier than after neutron damage.
Colorimetric Sensing by Using Allosteric‐DNAzyme‐Coupled Rolling Circle Amplification and a Peptide Nucleic Acid–Organic Dye Probe (2009)

Abstract Mit bloßem Auge : Die Wirkung eines RNA‐spaltenden allosterischen DNAzyms, das auf die Bindung eines Liganden reagiert, wurde mit einer Rolling‐Circle‐Amplifikation gekoppelt, um lange einzelsträngige DNA‐Moleküle für die kolorimetrische Sensorik zu erzeugen (siehe Schema). Bei der Hybridisierung der entstehenden DNA mit einer komplementären PNA‐Sequenz in Gegenwart eines doppelstrangbindenden Farbstoffs tritt eine Farbänderung von Blau nach Violett auf. magnified image
Metal–semiconductor interfacial reactions: Ni/Si system (1981)

Interfacial reactions between Si and deposited metals have been investigated by x-ray photoelectron spectroscopy (XPS) and channeling measurements with MeV 4He ions. This paper is concerned with reactions of Ni deposited at 10−10 Torr on clean Si and with the structure of the interface in the Si/Ni2Si/Ni structure. Both XPS and channeling measurements show that reactions occur where Ni is deposited at 10−10 Torr on Si: Si atoms are displaced from lattice sites, the Ni atoms are in an Si-rich environment, and the Ni/Si interface is graded in composition. Composition gradients are present at both interfaces in the Si/Ni2/Si/Ni system: at the Si/Ni2Si interface Ni atoms are in a more Si-rich environment than that found for Ni in Ni2Si or NiSi and at the Ni/Ni2Si interface Si atoms are in more Ni-rich environment than that found for Si in Ni2Si. In both deposited Ni on Si and the Si/Ni2Si/Ni structures, Ni atoms are found at the tetrahedral interstitial site in Si. For the Ni–Si system, cooling the substrate to ∠100 K slows down the reaction rate. The temperature dependence of the interfacial reactivity indicates the kinetic nature of metal–semiconductor interfaces.
Asymmetrical two-dimensional magnetic lattices for ultracold atoms (2010)

A simple method for implementing an asymmetrical two-dimensional magnetic lattice is proposed. The asymmetrical two-dimensional magnetic lattice is created by periodically distributing nonzero magnetic minima across the surface of a magnetic thin film, where the magnetic patterns are formed by milling $n\ifmmode\times\else\texttimes\fi{}n$ square holes on the surface of the film. The method is proposed for trapping and confining quantum degenerate gases, such as Bose-Einstein condensates and ultracold Fermi gases, prepared in low-magnetic-field-seeking states. Analytical expressions and numerical simulation results of the magnetic local minima are shown where we analyze the effect of changing the magnetic lattice parameters, such as the separation of the holes, the hole size, and external bias magnetic fields, to maintain and locate the nonzero local minima at a suitable distance above the film surface to avoid the effect of Majorana spin flips and the Casimir-Polder potential.
Synthesis and structure of divalent thulium borohydrides and their application in epsilon-caprolactone polymerisation (2011)

International audience
Cortisone and Peptic Ulcer (1963)

<h3>To the Editor:</h3> —In reply to the letter of Dr. Maghen, I have the following points to make. It is true that the control dogs did not receive placebos during the same period of time. However, previous work with several hundreds of dogs that received other drugs to evaluate their ulcerogenic capabilities seem to indicate that the stress from the injection was indeed minimal. Dogs that received injections for periods of months, of other hormones such as progesterone and diethylstilbestrol did not show any increase in the incidence of ulceration. For this reason, we did not see any purpose in repeating the injections of placebos in this study.
Clinical utility of profiling somatic alterations in Indian cancer patients using a multi-gene next generation sequencing (NGS) test. (2015)

e22127 Background: NGS allows for comprehensive profiling of a tumor genotype across multiple genes. Such molecular profiling can identify key driver mutations with potential to impact therapeutic decisions. We sought to evaluate the utility of an NGS multi-gene panel based approach in delivering therapeutically relevant insights that could affect treatment choices. Methods: DNA from formalin-fixed, paraffin-embedded blocks of 260 patients was sequenced on a MiSeq using a 48 gene hotspot panel from Illumina. Data was processed and analyzed using Strand NGS and mutations detected assessed for potential impact on response to therapy (actionability) and clinical relevance. Results: Clinical samples obtained encompassed 47 tumor types. The most common tumor types studied were breast (32%), colon (10%), lung (9%), sarcomas (7%) and ovarian (5%). The primary genes altered were TP53 (50%), PTEN (16%), PIK3CA (14%) and KRAS(13%). Most alterations detected affected the MAPK (24.5% across 20 cancers) or PI3K pathway (20.4% across 19 cancers). Among the more common tissue types (N > 10), the highest percentage of actionable alterations (AAs) was observed in colorectal cancer (82%) and lowest in sarcomas (53%). AAs that would not have been detected by conventional testing were observed in 24% (5/21) of lung and 20% (5/25) of colorectal cancers. In 45% of the cases, alterations detected could potentially impact response to therapy approved for that tumor type, while in 35% of the cases, AAs indicated probable response to alternative targeted therapy, either approved or in trials. Furthermore, more than one cancer pathway could be targeted in 15.6% of the cases, underscoring the relevance of NGS-based multi-gene testing to obtain accurate insights. In all, at least one AA was identified in 68% of the cases with the average number of AAs being 1.6, thus illustrating the suitability of this panel for a variety of tissue types. Conclusions: These data thus demonstrate the utility of multi-gene testing in a clinical setting by: (a) identifying additional clinically actionable variants compared to single gene testing (b) providing genotypically matched novel therapeutic options.
Clopidogrel preserves microvascular integrity in orthotopic tracheal transplants affected by obliterative bronchiolitis (2014)

Introduction: Survival after lung transplantation is mainly limited by the development of chronic lung allograft dysfunction (CLAD). The aim of this study was to investigate if platelet inhibition by clopidogrel has an influence on the microvascular integrity of orthotopic tracheal allografts and the formation of obliterative bronchiolitis, present in the majority of patients suffering from CLAD.
Intraoperative Characterization of Subthalamic Nucleus-to-Cortex Evoked Potentials in Parkinson’s Disease Deep Brain Stimulation (2021)

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson's disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed - one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the "start" and the "end" EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude (<i>p</i> < 0.05) and latency (<i>p</i> < 0.001), and the end, but not the start, EP magnitude has a significant relationship (<i>p</i> < 0.001, adjusted for random effects of subject) to ongoing high gamma (80-150 Hz) power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs.
Reverse remodelling, changes in diastolic function and their prognostic value compared to natriuretic peptides (2020)

Abstract Background Reverse remodelling (RR) is the recovery from left ventricular (LV) dilation and dysfunction in response to treatment for heart failure (HF). RR is usually associated with improved prognosis. The impact of RR on indices of diastolic function, and the relative prognostic value of RR, changes in diastolic function and natriuretic peptide levels are currently unknown. Methods We analysed data from patients with stable systolic HF (LV ejection fraction [LVEF] &amp;lt;50%) undergoing 2 transthoracic echocardiograms (TTE) within 12±2 months. RR was defined as a ≥15% reduction in LV end-systolic volume index (LVESVi). The follow-up started after the second TTE. Results 927 patients were evaluated (68±12 years; median LVEF 35% [interquartile interval 30–43%]; 27% women; 52% ischaemic aetiology). Patients experiencing RR (n=286, 31%) displayed more prominent positive changes in several parameters reflecting diastolic dysfunction, namely E/e' ratio, left atrial volume index (LAVi), and systolic pulmonary artery pressure (sPAP), as well as N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP; Figure). In the whole population, percent changes (Δ%) LVESVi displayed weak but significant correlations with Δ% E/e' (r=0.237, p&amp;lt;0.001), LAVi (r=0.316, p&amp;lt;0.001), and sPAP (r=0.158, p&amp;lt;0.001), and also with Δ% NT-proBNP (r=0.279, p&amp;lt;0.001). There were 123 cardiovascular deaths and 4 heart transplantations over 2.8 years (1.3–4.9). Δ% LVESVi, RR, Δ% sPAP and Δ% NT-proBNP were univariate predictors of this endpoint. In 2 multivariable models including Δ% sPAP and Δ% NT-proBNP and either RR or Δ% LVESVi, only Δ% NT-proBNP emerged as independent predictor of outcome (hazard ratio 1.01, 95% confidence interval 1.01–1.02; p&amp;lt;0.001). Conclusions A recovery of LV geometry is accompanied by positive modifications in several indices related to diastolic function, as well as a decrease in NT-proBNP levels. Percent changes in NT-proBNP over 12 months are stronger predictors of outcome than variations in LV geometry or sPAP. Funding Acknowledgement Type of funding source: None
Targeting p21-Dependent Pathways for Cell Death in Cancer Therapy (2009)

Checkpoint activation is a natural response to DNA damage that enables cells to take approp-riate action, which results in cells either living or dying. A major target in checkpoint response is the tumor suppressor p53, which becomes stabilized and activated following the post-translation modifications. The activated p53 then transactivates the downstream p21 gene to inhibit cyclin-dependent kinase (CDK), induce cell cycle arrest to allow DNA repair, and enable cells to survive. If DNA damage is excessive, then p53-dependent apoptosis is affected. Since cell cycle arrest precedes cell death, it is not surprising that checkpoint response has been correlated with apoptosis, and the possibility that these two processes cross-communicate is supported by evidence that p21, like p53, is a tumor suppressor, and its expression is downregulated in apoptosis-defective cancers. In addition to affecting apoptosis through checkpoint response, p21 can also induce this mode of cell death through a different mechanism that involves repression of anti-apoptotic genes. It becomes apparent that p21 may be an important component of not only checkpoint response, but also apoptosis.
Entschleimung und physikalische Raffination (von Raps- und Sonnenblumenöl) (1993)

Im Rahmen eines durchgängigen Anlagenkonzeptes für die physikalische Raffination von Raps- und Sonnenblumenöl wird über die mehrjährigen sehr guten Erfahrungen mit einem neuen Entschleimungsverfahren in großtechnischen Anlagen berichtet. Dieses Verfahren reicht auch unter schwankenden Eingangsbedingungen sehr niedrige Restschleimstoffgehalte als wesentliche Voraussetzung für eine erfolgreiche physikalische Raffination. Degumming and Physical Refining (of Rapeseed- and Sunflower Oil) The presented paper deals with the very good experiences made over a period of several years with a new degumming process applied in industrial-scale plants for physical refining of rapeseed oil and sunflower oil. This process allows, even under varying input conditions, to achieve very low contents of residual gummy substances, one of the preconditions for successful physical refining.
B11 Micro/nano machining of hardened steel with nano-accuracy by amplitude control sculpturing method in elliptical vibration cutting (2014)

This study presents the micro-/nano-structure machining of hardened steel by means of elliptical vibration cutting equipped with the ultra-precision amplitude control sculpturing method. Machining performance of the amplitude control sculpturing method is investigated, and the limitation in nano-scale machining is explored. In this method, machinable part geometry is essentially restricted by vibration/machining conditions and tool geometry. In addition, a considerable error between the amplitude command and the envelope of the tool trajectory is generated when the slope of the machining part geometry becomes steep. To overcome this error, a compensation method for the amplitude control command is proposed. In order to clarify the machining performance of the proposed technology, experimental investigations are conducted. By applying the proposed method, highly accurate machining of the sinusoidal sweep structure is attained with a machining error of less than 20 nm. The proposed sculpturing method is subsequently applied to the machining of a three-dimensional grid surface, which verifies the feasibility of the proposed amplitude control sculpturing method.
A Risk Management Framework for Cloud Migration Decision Support (2017)

Keywords: risk management framework; risk assessment; cloud migration; security; analytic hierarchy process (AHP); business value