gebhart/patrepeval huggingface dataset:
Direct Zinc Finger Protein Persulfidation by H2S Is Facilitated by Zn2+ (2019)

Abstract H 2 S is a gaseous signaling molecule that modifies cysteine residues in proteins to form persulfides (P‐SSH). One family of proteins modified by H 2 S are zinc finger (ZF) proteins, which contain multiple zinc‐coordinating cysteine residues. Herein, we report the reactivity of H 2 S with a ZF protein called tristetraprolin (TTP). Rapid persulfidation leading to complete thiol oxidation of TTP mediated by H 2 S was observed by low‐temperature ESI‐MS and fluorescence spectroscopy. Persulfidation of TTP required O 2 , which reacts with H 2 S to form superoxide, as detected by ESI‐MS, a hydroethidine fluorescence assay, and EPR spin trapping. H 2 S was observed to inhibit TTP function (binding to TNFα mRNA) by an in vitro fluorescence anisotropy assay and to modulate TNFα in vivo. H 2 S was unreactive towards TTP when the protein was bound to RNA, thus suggesting a protective effect of RNA.
Iodolactonization: Synthesis, Stereocontrol, and Compatibility Studies (2011)

Abstract Generalized iodolactonization conditions have been developed for the formation of both cis ‐ and trans ‐γ‐lactones from 3‐pentenoic acid derivatives containing various protected alcohol moieties. Kinetic control of the reaction using iodine and base at 0 °C for 6 h provided the cis ‐lactone with good selectivity (75:25), and thermodynamic control at room temperature for 24 h provided the trans ‐lactone with excellent selectivity (98:2).
Mapping of an epitope recognized by a neutralizing monoclonal antibody specific to toxin Cn2 from the scorpion Centruroides noxius, using discontinuous synthetic peptides (1999)

The Na+-channel-affecting toxin Cn2 represents the major and one of the most toxic components of the venom of the Mexican scorpion Centruroides noxius Hoffmann. A monoclonal antibody BCF2 raised against Cn2 has been shown previously to be able to neutralize the toxic effect of Cn2 and of the whole venom of C. noxius. In the present study the epitope was mapped to a surface region comprising the N- and C-terminal segments of Cn2, using continuous and discontinuous synthetic peptides, designed on the basis of the sequence and a three-dimensional model of Cn2. The study of peptides of varying length resulted in the identification of segments 5-14 and 56-65 containing residues essential for recognition by BCF2. The peptide (abbreviated SP7) with the highest affinity to BCF2 (IC50 = 5.1 microM) was a synthetic heterodimer comprising the amino acid sequence from position 3-15 (amidated) of Cn2, bridged by disulfide to peptide from position 54-66, acetylated and amidated. Similar affinity was found with peptide SP1 [heterodimer comprising residues 1-14 (amidated) of Cn2, bridged with synthetic peptide 52-66 (acetylated)]. SP1 and SP7 were used to induce anti-peptide antibodies in mouse and rabbit. Both peptides were highly immunogenic. The sera obtained were able to recognize Cn2 and to neutralize Cn2 in vitro. The most efficient protection (8.3 microgram Cn2 neutralized per mL of serum) was induced by rabbit anti-SP1 serum.
Applications of artificial intelligence for hypertension management (2021)

The prevalence of hypertension is increasing along with an aging population, causing millions of premature deaths annually worldwide. Low awareness of blood pressure (BP) elevation and suboptimal hypertension diagnosis serve as the major hurdles in effective hypertension management. The advent of artificial intelligence (AI), however, sheds the light of new strategies for hypertension management, such as remote supports from telemedicine and big data-derived prediction. There is considerable evidence demonstrating the feasibility of AI applications in hypertension management. A foreseeable trend was observed in integrating BP measurements with various wearable sensors and smartphones, so as to permit continuous and convenient monitoring. In the meantime, further investigations are advised to validate the novel prediction and prognostic tools. These revolutionary developments have made a stride toward the future model for digital management of chronic diseases.
Comparison of power definitions for reactive power compensation in nonsinusoidal conditions (2005)

Since the beginning of the power systems, harmonic distortion have been existed due to nonlinear equipments such as; generators, transformers motors etc. Moreover, harmonic pollution on power systems has dramatically increased in parallel with large proliferation of power electronic devices. Consequently, the reactive power compensation in nonsinusoidal conditions became one of the most important problems in power systems. This paper presents a comparison on widely accepted power definitions in a simple single phase circuits with nonsinusoidal waveforms of voltage and/or currents by giving particular emphasis to the reactive power compensation.
18F-FDG PET/CT for the Evaluation of Primary Eosinophilic Granuloma of the Hypothalamus (2018)

A 21-y-old man who presented with polyuria and polydipsia was discovered to have diabetes insipidus due to eosinophilic granuloma of the hypothalamus. <sup>18</sup>F-FDG PET/CT, which was performed as a metastatic work-up, revealed an intensely <sup>18</sup>F-FDG-avid hypothalamic mass and no other sites of disease.
Quality of life by smoking status in patients with metastatic or advanced NSCLC from Phase 2 clinical trial of veliparib with carboplatin and paclitaxel. (2016)

e20549 Background: A Phase 2 clinical trial of veliparib + carboplatin (C) and paclitaxel (P) in patients (pts) with previously untreated metastatic/advanced NSCLC showed that veliparib may improve survival compared to placebo and that smoking history was a strong predictor of efficacy for veliparib+CP. This study compares quality of life (QoL) by smoking status in pts receiving veliparib+CP vs placebo+CP. Methods: This study is a secondary analysis of a Phase 2 clinical trial (NCT01560104) where pts were randomized 2:1 to veliparib+CP (120mg BID) or placebo+CP for up to 6 treatment cycles (study period). Pts with ≥ 1 QoL measurement at baseline (pre-treatment initiation) and during ≥ 1 cycle were selected and stratified by smoking status in the year preceding the trial (smokers [S] vs non-smokers [NS]). Proportions of pts with a QoL improvement (QoL+)/deterioration (QoL-) from baseline achieving minimal important difference ( ≥ 10 points on a 100-point scale) across the study period were compared by treatment and smoking status using generalized estimating equation models adjusted for baseline QoL score, gender, and ECOG, for each of the 22 EORTC QLQ-C15-PAL/LC13 questionnaire items. Results: Among 143 pts (657 pt-cycles), mean age was 62 years, 67% were male, and 59% were S. In S, veliparib+CP pts had better or non-different QoL compared to placebo+CP pts; a higher proportion of veliparib+CP pts had QoL+ for dyspnea (odds ratio [OR] = 3.63) and a lower proportion of pts had QoL- for physical functioning (OR = 0.46), appetite loss (OR = 0.37), and dysphagia (OR = 0.12), all p < .05. In veliparib+CP pts, S had better or non-different QoL compared to NS (emotional functioning: both QoL+ and QoL- OR = 2.80 and 0.38, respectively; pain in chest: QoL+ OR = 3.86; coughing: QoL- OR = 0.48; all p < .05). The magnitude of the difference in QoL for S vs NS was larger or non-different in veliparib+CP pts compared to placebo+CP pts (dyspnea: QoL+ OR = 8.48; appetite loss: QoL+ OR = 11.54, QoL- OR = 0.27; dysphagia: QoL- OR = 0.05; all p < .05). Conclusions: Smokers receiving veliparib+CP had better or non-different QoL compared to both non-smokers receiving veliparib+CP and to smokers receiving placebo+CP. Clinical trial information: NCT01560104.
Die Identifizierung von Genen, die die Entwicklung bei Fliegen und Fischen steuern (Nobel‐Vortrag) (1996)

Die Identifizierung von Vertebraten‐Genen ist oft wegen ihrer Analogie zu Drosophila ‐Genen möglich. Sie ist für das Verständnis der Vertebraten‐Entwicklung auf genetischem Niveau von großer Bedeutung. Diese Homologie zeigt, daß einige Eigenschaften von Organismen unterschiedlicher Tierstämme konserviert sind und damit ein gemeinsamer Entwicklungsplan vorliegen muß. Ein Vergleich der Musterbildung bei Fliegen und Vertebraten gelang beispielsweise durch Mutagenesen am Zebrafisch.
Predicting Off‐Target Effects of Therapeutic Antiviral Ribonucleosides (2018)

Therapeutic ribonucleoside inhibitors have been recognized as one of the most promising classes of antiviral compounds currently being developed to treat RNA virus infections. The ability of antiviral ribonucleosides to be incorporated in vivo will depend on the sizes of the intracellular antiviral ribonucleoside triphosphate pool and natural ribonucleoside triphosphate pool with which the analogue competes. It has long been recognized that the human mitochondrial DNA polymerase has been an “off-target” of nucleoside reverse transcriptase inhibitors (NRTIs) used for the treatment of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. The biochemical tools used to study substrate utilization by mitochondrial RNA polymerase (POLRMT) in vitro were recently developed. These advancements have allowed the determination of the utilization of antiviral ribonucleoside triphosphates by POLRMT and so predicting unwanted “off-target” inhibition of mitochondrial transcription. The limited diversity of both the nuclear genome and mtDNA can essentially desensitize cells to changes in proper mitochondrial function.
Regulation of Phosphatidylcholine Biosynthesis in Saccharomyces cerevisiae (1971)

Evidence is presented which indicates that the biosynthesis of phosphatidylcholine by the methylation pathway in growing cultures of Saccharomyces cerevisiae is repressed by the presence of choline in the growth medium. This result, obtained previously for glucose-grown cells, was also observed for lactate-grown cells, of which half of the phosphatidylcholine is mitochondrial. A respiration-deficient mutant of the parent wild-type strain has been studied, and its inability to form functional mitochondria cannot be due to an impaired methylation pathway, as it has been shown to incorporate (14)C-CH(3)-methionine into all of the methylated glycerophosphatides. The incorporation rate is depressed by the inclusion of 1 mm choline in the growth medium, suggesting a regulatory effect similar to that demonstrated for the wild-type strain. The effects of choline on the glycerophospholipid composition of lactate and glucose-grown cells is presented. The repressive effects of the two related bases, mono- and dimethylethanolamine, were examined, and reduced levels of (14)C-CH(3)-methionine incorporation were found for cells grown in the presence of these bases. The effect of choline on the methylation rates is reversible and glucosegrown cells regain the nonrepressed level of methylation activity in 60 to 80 min after removal of choline from the growth medium.
Arteritic Anterior Ischaemic Optic Neuropathy and Chronic Cough as Presenting Features of Churg-Strauss Syndrome (2011)

A 57-year-old man presented with severe, painless, stepwise vision loss in one eye over 24 hours. Fundus examination showed pallid optic disc oedema with cilioretinal artery occlusion. A retinal fluorescein angiogram showed patchy choroidal hypoperfusion of the affected eye, consistent with arteritic anterior ischaemic optic neuropathy (AION). Temporal artery biopsy revealed non-giant cell periarteritis. A systemic evaluation discovered a symptom complex of asthma, eosinophilia, and pulmonary infiltrates, suggesting Churg-Strauss syndrome. The patient was successfully treated with oral corticosteroid and metrotrexate, with stabilization of vision and improvement of systemic symptoms.
Clinical and non-invasive evaluation of 12% ammonium lactate emulsion for the treatment of dry skin in atopic and non-atopic subjects. (1992)

Clinical dryness of the leg skin is a common problem among dermatological patients. The efficacy and safety of 12% ammonium lactate emulsion (Keratisdin) for the treatment of dry skin on the legs of atopic and non-atopic subjects has been assessed by clinical criteria and by five different non-invasive methods. These methods measure biophysical parameters such as electrical capacitance of stratum corneum, skin surface lipids, transepidermal water loss (TEWL), skin surface topography (scanning electron microscopy and image analysis) as well as the biomechanical properties of the skin. Treatment with the test emulsion significantly reduced the severity scores for dryness, desquamation and pruritus when measured 15 days later. All patients tested showed a significant increase in electrical capacitance, skin surface lipids, extensibility and firmness of the skin, and an improvement in the skin barrier function and skin surface topography. This study showed that non-invasive techniques are excellent complementary tools in clinical studies.
Detection and measurement of small vibrations using electronic speckle pattern interferometry (1977)

We describe a new method for real-time detection and measurement of small vibrations, based on phase modulation in time-average electronic speckle pattern interferometry. The modulation frequency is shifted relative to the vibration frequency, which makes the intensity of the reconstructed image vary at the difference frequency. The amplitude detection limits are about 20 A by visual observation and 0.1 A by photoelectric measurement using a lockin technique. No auxiliary system for fringe stabilization is required. At higher amplitude levels we can study the deformation of the object in slow motion. Measurements on different objects, including human ear preparation, are presented.
ChemInform Abstract: Is Through‐Bond Dihydroaromaticity Attainable? Preparation of (4,5) Dihomotropone, Investigation of Its Ground‐State Properties, and an Attempt to Generate the Dihomotropylium Cation. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Zundel-Type H-Bonding in Biomolecular Ions (2014)

Using quantum chemical calculations and infrared multiphoton dissociation (IRMPD) spectroscopy in the fingerprint and X-H stretching regions, we demonstrate here that the all-Ala (b6) fragment ion features a macrocyclic structure with C(2) symmetry. For this structure, the ionizing proton is equally shared by the Ala(1) and Ala(4) amide oxygens in a Zundel-type symmetric (X…H(+)…X) H-bond.
SXR, a novel steroid and xenobioticsensing nuclear receptor (1998)

An important requirement for physiologic homeostasis is the detoxification and removal of endogenous hormones and xenobiotic compounds with biological activity. Much of the detoxification is performed by cytochrome P-450 enzymes, many of which have broad substrate specificity and are inducible by hundreds of different compounds, including steroids. The ingestion of dietary steroids and lipids induces the same enzymes; therefore, they would appear to be integrated into a coordinated metabolic pathway. Instead of possessing hundreds of receptors, one for each inducing compound, we propose the existence of a few broad specificity, low-affinity sensing receptors that would monitor aggregate levels of inducers to trigger production of metabolizing enzymes. In support of this model, we have isolated a novel nuclear receptor, termed the steroid and xenobiotic receptor (SXR), which activates transcription in response to a diversity of natural and synthetic compounds. SXR forms a heterodimer with RXR that can bind to and induce transcription from response elements present in steroid-inducible cytochrome P-450 genes and is expressed in tissues in which these catabolic enzymes are expressed. These results strongly support the steroid sensor hypothesis and suggest that broad specificity sensing receptors may represent a novel branch of the nuclear receptor superfamily.
A mouse myeloma variant with a defect in light chain synthesis (1979)

A spontaneous assembly variant, B 50, has been isolated from the MPC-11 mouse myeloma cell line. This variant synthesizes fewer light chains per cell than the parent resulting the production of a slight molar excess of heavy chains. These changes are associated with a delay and change in the pathway of assembly and a delay in secretion. Spontaneous revertants of B 50 have been obtained, all of which synthesize normal amounts of light chains and assemble and secrete the immunoglobulin molecule through the same pathways and with the same kinetics as the parental cells. A comparison of the tryptic-chymotryptic peptides of the parental, variant and revertant heavy and light chains did not reveal any differences. These studies indicate that variants in mouse myeloma cells can arise with defects in the quantitative expression of the immunoglobulin gene and suggest that the presence of excess light chains facilitates the assembly and secretion of some immunoglobulin molecules.
BLOOD IN PEARL (1987)

BLOOD IN PEARL HUGH WHITE HUGH WHITE Search for other works by this author on: Oxford Academic Google Scholar The Review of English Studies, Volume XXXVIII, Issue 149, February 1987, Pages 1–13, https://doi.org/10.1093/res/XXXVIII.149.1 Published: 01 February 1987
TOUGHREACT: a new code of the TOUGH Family for Non-Isothermal multiphase reactive geochemical transport in variably saturated geologic media (2003)

Coupled modeling of subsurface multiphase fluid and heat flow, solute transport and chemical reactions can be used for the assessment of acid mine drainage remediation, waste disposal sites, hydrothermal convection, contaminant transport, and groundwater quality. We have developed a comprehensive numerical simulator, TOUGHREACT, which considers non-isothermal multi-component chemical transport in both liquid and gas phases. A wide range of subsurface thermo-physical-chemical processes is considered under various thermohydrological and geochemical conditions of pressure, temperature, water saturation, and ionic strength. The code can be applied to one-, two- or three-dimensional porous and fractured media with physical and chemical heterogeneity.
Experimentelle Untersuchungen von Einflußfaktoren auf die Selbstzündung von gasförmigen und flüssigen Brennstofffreistrahlen. (KIT Scientific Reports ; 7555) (2010)

Zur Untersuchung der Einflussfaktoren auf die Selbstzündung des gasförmigen Brennstofffreistrahls wird eine erweiterte Zündwahrscheinlichkeit erstellt. Sie beinhaltet die Einflüsse der Zündgrenzen, der lokalen Mischungstemperatur und der Strömung. Daneben wird der Einfluss der charakteristischen Größen des Brennstoffsprays auf die Selbstzündung untersucht.
Effect of atrial fibrillation ablation on left atrial contractile function in patients with paroxysmal atrial fibrillation and a relatively well preserved atrial function (2009)

In patients with paroxysmal AF and relatively well preserved LA function, AF ablation leads to no significant deterioration of atrial function.
Accelerated apoptosis in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus type-1 infected patients and in CD4 cross-linked PBMCs from normal individuals (1993)

Abstract This study investigates apoptosis as a mechanism for CD4+ T-cell depletion in human immunodeficiency virus type-1 (HIV-1) infection. Although several recent studies have shown that T cells of HIV-infected individuals show enhanced susceptibility to cell death by apoptosis, the mechanisms responsible for apoptosis are largely unknown. By using a flow cytometric technique and by morphology, we have quantitated the percentage of cells undergoing apoptosis in peripheral blood mononuclear cells (PBMCs) from HIV-seronegative donors and from HIV- infected asymptomatic patients. The PBMCs were cultured without any stimulus or with staphylococcus enterotoxin B, anti-T-cell receptor (TCR) alpha beta monoclonal antibody WT-31, or phytohemagglutinin for periods up to 6 days. In addition, we sought to determine whether cross- linking of CD4 followed by various modes of TCR stimulation in vitro could induce apoptosis in normal PBMCs. Here we show that (1) patient PMBCs undergo marked spontaneous apoptosis; (2) stimulation of T cells of patients as well as normal donors results in increased apoptosis; and (3) cross-linking of CD4 molecules is sufficient to induce apoptosis in CD4+ T cells if cross-linking is performed in unfractioned PBMCs, but not if CD4 molecules are cross-linked in purified T-cell preparations. These observations strongly suggest that accelerated cell death through apoptosis plays an important role in the pathogenesis of HIV-1 infection. At the same time, our observations implicate cross- linking of CD4 in vivo as a major contributor to this mechanism of accelerated cell death in HIV infection.
Abstract B008: Treatment of IDO1 and TDO2 positive tumors with a kynurenine-degrading enzyme: A highly differentiated approach from IDO1 inhibition (2019)

Abstract Despite the sustained clinical benefit demonstrated by immune checkpoint inhibitors, a majority of patients derive minimal or no appreciable benefit, indicating the urgent need to incorporate novel immunomodulatory targets and therapeutic strategies. Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase 2 (TDO2) catalyze the first and rate-limiting step in the immunosuppressive tryptophan/kynurenine pathway and are both upregulated in a number of tumor types. Although small-molecule IDO1 inhibitors are being clinically evaluated in several tumor types, so far they have not demonstrated significant clinical benefits either as a single agent or in combination with immune checkpoint inhibition. We are developing pegylated kynureninase (Kynase), a kynurenine degrading enzyme, to treat a broader population with IDO1 and/or TDO2 expressing tumors. We believe that a more robust antitumor immune response can be achieved by depleting kynurenine, produced by both IDO1 and TDO2, with Kynase, than by inhibiting only IDO1. The human Kynase (HsKYN) has been successfully engineered to exhibit vastly improved catalytic activity and stability toward kynurenine over the wild-type human enzyme. HsKYN achieved durable and near complete plasma kynurenine depletion in mice, rats and non-human primates. HsKYN demonstrated single agent efficacy in CT26, MC38 and B16-IDO syngeneic mouse models. Tumor gene expression analysis using NanoString revealed that HsKYN treatment upregulated T-cell and NK cell activation signature. More importantly, HsKYN significantly increased the tumor-infiltrating CD8 T-cells and their activation/polyfunctionality, and reduced the Treg population. As a direct comparison, the lead IDO1 inhibitor epacadostat did not impose any meaningful effects on the same immune cell populations. Furthermore, HsKYN showed beneficial combination efficacy with anti-PD-1 that was superior to combined Epacadostat / anti-PD-1. Evidence to date suggest that HsKYN is well tolerated in multiple species. Therefore, immunoprofiling, efficacy and safety results strongly support that Kynase is a more effective therapeutic approach than IDO1 inhibition. HsKYN is moving toward clinical development for treatment of cancers where IDO1 and/or TDO2 pathways play a significant immunosuppressive role. Citation Format: Silvia Coma, Jillian Cavanaugh, James Nolan, Jeremy Tchaicha, Karen McGovern, Everett Stone, John Blazeck, Candice Lamb, George Georgiou, Mark G Manfredi, Michelle Zhang. Treatment of IDO1 and TDO2 positive tumors with a kynurenine-degrading enzyme: A highly differentiated approach from IDO1 inhibition [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B008.