gebhart/patrepeval huggingface dataset:
Trypsinogen and chymotrypsinogen: the mysterious hyper‐reactivity of selected cysteines is still present after their divergent evolution (2021)

An enigmatic and never described hyper-reactivity of most of the cysteines resident in the reduced, molten globule-like intermediate of a few proteins has been recently discovered. In particular, all ten cysteines of chymotrypsinogen showed hundred times increased reactivity against hydrophobic reagents. A single cysteine (Cys1) was also found thousand times more reactive toward GSSG, making speculate that a single glutathionylation could represent the primordial event of its oxidative folding. In the present study, we compare these kinetic properties with those present in trypsinogen taken in its reduced, molten globule-like intermediate and identify the origin of these unusual properties. Despite the divergent evolution of these two proteins, the different amount of disulfides and the very different 3D localization of three disulfides, their hyper-reactivity toward hydrophobic thiol reagents and disulfides is very similar. Mass spectrometry identifies two cysteines in trypsinogen, Cys148 and Cys197, 800 times more reactive toward GSSG than an unperturbed protein cysteine. These results point toward a stringent and accurate preservation of these peculiar kinetic properties during a divergent evolution suggesting some important role, which at the present can only be hypothesized. Similar extraordinary hyper-reactivity has been found also in albumin, ribonuclease, and lysozyme confirming that it cannot be considered a kinetic singularity of a single protein. Interestingly, the very flexible and fluctuating structures like those typical of the molten globule status prove capable of enabling sophisticated actions typical of enzymes such as binding to GSSG with relevant specificity and high affinity (K<sub>D</sub> = 0.4 mm) and accelerating the reaction of its cysteines by thousands of times.
Sigmund Freud's Discovery of Psychoanalysis (2013)

Sigmund Freud’s discovery of psychoanalysis explores links between Freud’s development of his thinking and theory and his personal emotional journey. It follows his early career as a medical student, researcher and neurologist, and then as a psychotherapist, to focus on the critical period 1895-1900. During these years Freud submitted himself to the process that has become known as his ‘self-analysis’, and developed the core of his psychoanalytic theory. Drawing on Freud’s letters to his friend and confidant Wilhelm Fliess, and on selected psychoanalytic writings in particular his ‘dream of Irma’s injection’, Paul Schimmel formulates psychoanalytic dimensions to the biographical ‘facts’ of Freud’s life. In 1900 Freud wrote that he was ‘not a thinker’ but ‘a conquistador’. In reality he was both, and was engaged in a lifelong emotional struggle to bring these contradictory sides of his personality into relationship. His psychoanalytic discoveries are conceptualized in the context of his need to achieve integration within his psyche, and in particular to forge a more creative collaboration between ‘conquistador’ and ‘thinker’. Sigmund Freud’s discovery of psychoanalysis will be of interest to psychoanalysts, psychoanalytic psychotherapists, academics and teachers of psychoanalysis, and to all serious students of the mind.
Enzymatic glycan remodeling–metal free click (GlycoConnect™) provides homogenous antibody-drug conjugates with improved stability and therapeutic index without sequence engineering (2022)

Antibody-drug conjugates (ADCs) are increasingly powerful medicines for targeted cancer therapy. Inspired by the trend to further improve their therapeutic index by generation of homogenous ADCs, we report here how the clinical-stage GlycoConnect™ technology uses the globally conserved N-glycosylation site to generate stable and site-specific ADCs based on enzymatic remodeling and metal-free click chemistry. We demonstrate how an engineered endoglycosidase and a native glycosyl transferase enable highly efficient, one-pot glycan remodeling, incorporating a novel sugar substrate 6-azidoGalNAc. Metal-free click attachment of an array of cytotoxic payloads was highly optimized, in particular by inclusion of anionic surfactants. The therapeutic potential of GlycoConnect™, in combination with HydraSpace™ polar spacer technology, was compared to that of Kadcyla® (ado-trastuzumab emtansine), showing significantly improved efficacy and tolerability.
Nanochannels in Photoactive Polymeric Cu(I) Compatible for Efficient Micellar Catalysis: Sustainable Aerobic Oxidations of Alcohols in Water (2021)

Upon visible-light irradiation, the heterogeneous polymer of PDI–Cu(I)–PDI (PDI = perylene diimide) generates charge transfer states that are subsequently quenched by molecular oxygen for their participation in redox activity. This insoluble polymeric Cu(I) is catalytically active for the oxidation of benzylic alcohols to corresponding aldehydes when suspended in dynamic micelles of PS-750-M. A broad substrate scope, excellent selectivity, and no over-oxidation reveal the catalyst robustness. The catalytic activity, control experiments, and time-dependent DFT calculations show the charge transfer states. The polymeric catalyst is entirely recyclable, as evidenced by the recycle studies using Scott’s recyclability test. The morphology, structure, copper’s oxidation state, and the catalyst’s thermal stability are determined by SEM, XPS, and TGA analysis.
Reactivity of monoclonal antibodies EG1 and EG2 with eosinophils and their granule proteins (1999)

Use of the murine monoclonal antibodies EG1 and EG2 has been based on the assumption that EG2 recognizes activated eosinophils. We examined the reactivity of EG1 and EG2 with eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), and stimulated and nonstimulated eosinophils from normal donors. By radioimmunoassay, EG1 recognized only ECP, whereas EG2 recognized both ECP and EDN. By Western blot, EG1 reacted with ECP, EG2 reacted with both ECP and EDN, but EG2 could not distinguish between lysates of stimulated and nonstimulated eosinophils. By immunofluorescence, EG1 and EG2 at 20 microg/mL stained 95-100% of nonstimulated eosinophils, regardless of fixative; EG1 and EG2 at 0.1 microg/mL stained 61-90% of acetone- and paraformaldehyde-fixed and only 5-21% of methanol-fixed nonstimulated eosinophils. Thus, the reactivity of EG1 and EG2 with eosinophils depends on the method of fixation and antibody concentration; and EG2, in contrast to previous reports, cannot reliably discriminate between resting and activated eosinophils.
Discovery of Benzothiazole Scaffold-Based DNA Gyrase B Inhibitors (2016)

Bacterial DNA gyrase and topoisomerase IV control the topological state of DNA during replication and are validated targets for antibacterial drug discovery. Starting from our recently reported 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole-based DNA gyrase B inhibitors, we replaced their central core with benzothiazole-2,6-diamine scaffold and interchanged substituents in positions 2 and 6. This resulted in equipotent nanomolar inhibitors of DNA gyrase from Escherichia coli displaying improved inhibition of Staphylococcus aureus DNA gyrase and topoisomerase IV from both bacteria. Compound 27 was the most balanced inhibitor of DNA gyrase and topoisomerase IV from both E. coli and S. aureus. The crystal structure of the 2-((2-(4,5-dibromo-1H-pyrrole-2-carboxamido)benzothiazol-6-yl)amino)-2-oxoacetic acid (24) in complex with E. coli DNA gyrase B revealed the binding mode of the inhibitor in the ATP-binding pocket. Only some compounds possessed weak antibacterial activity against Gram-positive bacteria. These results provide a basis for structure-based optimization toward dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.
Effect of Endothelin-1 on Baroreflexes and the Cardiovascular Action of Clonidine in Conscious Rabbits (2016)

We studied the influence of pretreatment with endothelin-1 on cardiac baroreflexes and on the effect of clonidine on blood pressure and heart rate. In order to avoid the complication of the direct vasoconstrictor effects of endothelin-1, initial dose-response studies in animals treated with a ganglion blocker were performed. Intravenous administration of 50, 200, and 1200 ng/kg of endothelin-1 produced biphasic changes in blood pressure, consisting of an immediate depressor response, followed by a long lasting and dose-dependent pressor effect (peak response 3 ± 1, 9 ± 3, and 33 ± 5 mmHg, respectively). Thus, the 50 ng/kg dose of endothelin-1 was used in subsequent studies. Conscious rabbits were pretreated on separate days with endothelin-1, either intravenously (50 ng/kg) or intracisternally (10 and 50 ng/kg), or with vehicle. The animals then received an intravenous dose (20 μg/kg) or an intracisternal dose (1 μg/kg) of clonidine and the effects on blood pressure and heart rate were measured. In vehicle-treated rabbits, the intravenous administration of clonidine induced a significant decrease in blood pressure and heart rate (15 min after injection: -15.7 ± 4.7 mmHg and -33 ± 4 b/min, respectively). Similarly, the intracisternal injection of clonidine lowered blood pressure (-16.0 ± 2.5 mmHg), but produced a less pronounced bradycardia (-18 ± 4 b/min). Endothelin pretreatment, either 50 ng/kg centrally or peripherally, had no significant effect on the hypotension or bradycardia produced either by central or peripheral injection of clonidine. At this dose, endothelin by itself did not produce significant changes in blood pressure or heart rate. There was a reduction of the gain of the baroreceptor-heart rate reflex with intracisternal endothelin-1. These results suggest that central 2-adrenoceptor mechanisms involved in clonidine-induced hypotension and bradycardia do not appear to be influenced by activation of endothelin receptors.
Extending Hollow Cathode Life for Electric Propulsion for Long-Term Missions (2004)

This paper will present our understanding of the hollow cathode barium depletion mechanism and the design required to achieve the required life.
Final Report Systems Level Analysis of the Function and Adaptive Responses of Methanogenic Consortia (2015)

The purpose of this research was to determine whether the syntrophic microbial associations that are central to the functioning of methane-producing terrestrial wetlands can be predictively modeled with coupled multi-species genome-scale metabolic models. Such models are important because methane is an important greenhouse gas and there is a need to predictively model how the methane-producing microbial communities will respond to environmental perturbations, such as global climate change. The research discovered that the most prodigious methane-producing microorganisms on earth participate in a previously unrecognized form of energy exchange. The methane-producers Methanosaeta and Methanosarcina forge biological electrical connections with other microbes in order to obtain electrons to reduce carbon dioxide to methane. This direct interspecies electron transfer (DIET) was demonstrated in complex microbial communities as well as in defined co-cultures. For example, metatranscriptomic analysis of gene expression in both natural communities and defined co-cultures demonstrated that Methanosaeta species highly expressed genes for the enzymes for the reduction of carbon dioxide to methane. Furthermore, Methanosaeta’s electron-donating partners highly expressed genes for the biological electrical connections known as microbial nanowires. A series of studies involving transcriptomics, genome resequencing, and analysis of the metabolism of a series of strains with targeted gene deletions, further elucidated the mechanisms and energetics of DIET in methane-producing co-cultures, as well as in a co-culture of Geobacter metallireducens and Geobacter sulfurreducens, which provided a system for studying DIET with two genetically tractable partners. Genome-scale modeling of DIET in the G. metallireducens/G. sulfurreducens co-culture suggested that DIET provides more energy to the electron-donating partner that electron exchange via interspecies hydrogen transfer, but that the performance of DIET may be strongly influenced by environmental factors. These studies have significantly modified conceptual models for carbon and electron flow in methane-producing environments and have developed a computational framework for predictive modeling the influence of environmental perturbations on methane-producing microbial communities. The results have important implications for modeling the response of methane-producing microbial communities to climate change as well as for the bioenergy strategy of converting wastes and biomass to methane.
The journey to legalize cannabis in Canada (2018)

Drawing on current research and available technology, as well as best practices from around the world, Canada's goal of reducing traffic fatalities due to drug impaired driving will incorporate effective legislation, enforcement based on proven methods of detection paired with increased use of Standardized Field Sobriety Tests, and increased public education and awareness of the effects of Cannabis on driving. Canada has taken a proactive approach to this by forming a federal Task Force on Cannabis Legalization and Regulation, which submitted its final report (A Framework for the Legalization and Regulation of Cannabis in Canada) to the Government of Canada on November 30, 2016.
High performance superconducting thin films on large area substrates (1993)

The first fabrication of 3-in-diameter, thin films of thallium-based superconductors is reported. (Tl/sub 0.5/Pb/sub 0.5/)Sr/sub 2/Ca/sub 2/Cu/sub 3/O/sub 9/ thin films on LaAlO/sub 3/ are found to display the best surface resistance (R/sub s/) properties of any superconductor at higher temperatures and show approximately 50* better performance than copper at 100 K and 10 GHz. A Tl/sub 2/Ba/sub 2/CaCu/sub 2/O/sub 8/ thin film, processed as a 1.8-m-long, 10- mu m-wide meander line carries about 1*10/sup 7/ A/cm/sup 2/ at 4.2 K and 2*10/sup 6/ A/cm/sup 2/ at 80 K. The thallium-based superconductors are compared to YBa/sub 2/Cu/sub 3/O/sub 7/ with respect to T/sub c/, R/sub s/, and Q.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Pollution Detection on Rail Surface for Adhesion Evaluation Using Multispectral Images (2017)

There is a continuous rise of the number of trains' passengers to transport, therefore a densification of traffic is studied. For safety reasons, it becomes necessary to know the wheel-rail contact condition, in traffic, as it affects driving variables as adherence. The latest determines passenger's safety and the proper functioning of train equipment but it is often deteriorated due to recurrent pollution of the rail. From the analysis of the rolling surface, one can know if the rail is polluted or not and extract the kind of pollution and its influence on the train driving. The aim of this work is to contribute to guarantee and improve passengers' safety. In this paper, we propose a method for pollution detection and clustering, as a first step to the rail surface characterization. Methods using multispectral image analysis, specific data calibration, and hierarchical clustering based on Non Negative Matrix Factorization (NMF) are used.
The Generation of 1.2 μJ Pulses From a Mamyshev Oscillator Based on a High Concentration, Large-Mode-Area Yb-Doped Fiber (2022)

We demonstrate a high-energy and high-average power Mamyshev oscillator based on a high performance large-mode-area step-index germanosilicate-cladding Yb-doped fiber. The oscillation of higher-order modes is effectively suppressed by employing appropriate intracavity spatial mode filtering, allowing significant scaling of single pulse energy. The laser directly generates a nearly diffraction-limited beam with an average power of 17 W operating at the fundamental repetition rate of 14.01 MHz, corresponding to a pulse energy of 1.2 μJ. The pulses could be externally dechirped to ∼58 fs, leading to a peak power of ∼13 MW. To the best of our knowledge, this is the highest pulse energy with sub-100 fs duration ever obtained directly from a mode-locked fiber oscillator.
An L-band Radio Frequency Interference (RFI) detection and mitigation testbed for microwave radiometry (2007)

A microwave radiometer specifically designed to detect and mitigate many types of Radio Frequency Interference (RFI) is described. The L-band RFI Detection and Mitigation Testbed (DetMit Testbed) will not be optimized for radiometric observation as much as it is optimized for flexibility in the presence of RFI. While the DetMit Testbed will be a fully functional polarimetric L-band radiometer, the ultimate application of this instrument is not so much brightness measurements as it will be validation of RFI mitigation strategies for employment in future L-band (and other frequency) radiometers. The design approaches for the L-band RFI Detection and Mitigation Testbed are expected to apply to C- band and X-band, and presumably also to other frequencies of interest that experience RFI.
Synthesis and Biological Profile of the pan-Vascular Endothelial Growth Factor Receptor/Tyrosine Kinase with Immunoglobulin and Epidermal Growth Factor-Like Homology Domains 2 (VEGF-R/TIE-2) Inhibitor 11-(2-Methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4<i>H</i>-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (CEP-11981): A Novel Oncology Therapeutic Agent (2011)

A substantial body of evidence supports the utility of antiangiogenesis inhibitors as a strategy to block or attenuate tumor-induced angiogenesis and inhibition of primary and metastatic tumor growth in a variety of solid and hematopoietic tumors. Given the requirement of tumors for different cytokine and growth factors at distinct stages of their growth and dissemination, optimal antiangiogenic therapy necessitates inhibition of multiple, complementary, and nonredundant angiogenic targets. 11-(2-Methylpropyl)-12,13-dihydro-2-methyl-8-(pyrimidin-2-ylamino)-4H-indazolo[5,4-a]pyrrolo[3,4-c]carbazol-4-one (11b, CEP-11981) is a potent orally active inhibitor of multiple targets (TIE-2, VEGF-R1, 2, and 3, and FGF-R1) having essential and nonredundant roles in tumor angiogenesis and vascular maintenance. Outlined in this article are the design strategy, synthesis, and biochemical and pharmacological profile for 11b, which completed Phase I clinical assessing safety and pharmacokinetics allowing for the initiation of proof of concept studies.
Synthesis and Characterization of Aluminum and Gallium Complexes of Heterocyclic Carboxaldehyde Thiosemicarbazones. Single-Crystal Structure of [(MeAl){NC<sub>4</sub>H<sub>3</sub>CHNNC(S)N<i><sup>i</sup></i>C<sub>3</sub>H<sub>7</sub>}(AlMe<sub>2</sub>)]<sub>2</sub>and (GaMe<sub>2</sub>)<sub>2</sub>[SC<sub>4</sub>H<sub>3</sub>CHNNC(S)NPh] (1997)

Novel tetranuclear metal complexes with the formula [(MeM){NC4H3CHNNC(S)NR}(MMe2 )]2 (M = Al, R = iC3H7 (1); M = Ga, R = iC3H7 (2); M = Al, R = Me (3); M = Ga, R = Me (4)) result when pyrrolecarboxaldehyde thiosemicarbazone ligands are mixed with trimethylaluminum and -gallium. Four dinuclear metal compounds with the formula (MMe2)2[SC4H3CHNNC(S)NR] (M = Al, R = iC3H7 (5); M = Ga, R = iC3H7 (6); M = Al, R = C6H5 (7); M = Ga, R = C6H5 (8)) were synthesized by the methane elimination reaction of thiophenecarboxaldehyde thiosemicarbazones with trimethylaluminum and -gallium. The X-ray crystal structures of 1 and 8 are described. The structural data revealed that 1 is a tetranuclear aluminum compound with an eight-membered ring system and 8 is a dinuclear gallium compound with a weak interaction between the pendant thiophene and the gallium center.
Novel CCD-based pH imaging sensor (1999)

We propose and demonstrate a novel pH imaging sensor based on the Charge Coupled Device (CCD) technology. This device consists of pH sensing parts, which sense pH value and transform a pH value to electric charges, and conventional CCD parts, which transfer the electric charges to read out circuit. A thin Si/sub 3/N/sub 4/ film which acts as the hydrogen ion-sensitive membrane was used in the pH sensing film. The prototype devices were fabricated and was confirmed the device operation using pH equivalent voltages. It was found that the output signal from the imaging sensor was lineally changed from pH 0 to 14 and successfully observed a pH image on a black and white TV monitor.
An E Box Mediates Activation and Repression of the Acetylcholine Receptor δ-Subunit Gene during Myogenesis (1993)

The genes encoding the skeletal muscle acetylcholine receptor (AChR) are induced during muscle development and are regulated subsequently by innervation. Because both the initiation and the subsequent regulation of AChR expression are controlled by transcriptional mechanisms, an understanding of the steps that regulate AChR expression following innervation is likely to require knowledge of the pathway that activates AChR genes during myogenesis. Thus, we sought to identify the cis-acting sequences that regulate expression of the AChR delta-subunit gene during muscle differentiation. We transfected muscle and nonmuscle cell lines with gene fusions between 5'-flanking DNA from the AChR delta-subunit gene and the human growth hormone gene, and we show here that 148 bp of 5'-flanking DNA from the AChR delta-subunit gene contains two regulatory elements that control muscle-specific gene expression. One element is an E box, which is important both for activation of the delta-subunit gene in myotubes and for its repression in myoblasts and nonmuscle cells. Mutation of this E box, which prevents binding of MyoD-E2A and myogenin-E2A heterodimers, decreases expression in myotubes and increases expression in myoblasts and nonmuscle cells. An E-box binding activity, which does not contain MyoD, myogenin, or E2A proteins, is present in muscle and nonmuscle cells and may be responsible for repressing the delta-subunit gene in myoblasts and nonmuscle cells. An enhancer, which lacks E boxes, is also required for expression of the delta-subunit gene but does not confer muscle-specific expression.
A Catalyst‐Economic One‐Pot Protocol for the Synthesis and Conversion of Functionalized Vinylstannanes (2013)

Abstract A wide range of functionalized compounds can easily be obtained by a Pd‐catalyzed one‐pot hydrostannylation/elimination/distannylation/radical allylation sequence. The Pd catalyst used can be involved in up to five different reaction steps.
Isolation and Characterization of Novel Plant Growth-Promoting Bacteria from the Fronds of Duckweed (2021)

本研究では3種類のウキクサ亜科植物の葉状体から分離された微生物ライブラリーから植物生育促進細菌（plant growth-promoting bacteria; PGPB）を探索した。計25株を二段階のスクリーニングに供したところ、SP－2－C10株のみが通過した。この細菌株は葉状体から取得された初めてのPGPBであり、また、希少な細菌属であるAquidulcibacterに属していた。SP－2－C10株は無菌条件下で細菌非接種のコウキクサ（Lemna minor）に比べ、最大3.6倍の生育促進効果を示した。また、様々な競合微生物が存在する下水二次処理水中でもコウキクサに対する高い生育促進効果を示すことが明らかとなった（2.1倍）。
Density of quaternary glasses in the MgO‐CaO‐Al <sub>2</sub> O <sub>3</sub> ‐SiO <sub>2</sub> ‐system—modeling vs measurement (2017)

Abstract The densities of quaternary glass‐forming systems within the CaO‐MgO‐Al 2 O 3 ‐SiO 2 ‐composition ( CMAS ) were evaluated. Their compositions differed not more than 5 mol% for each component from each other. After melting, the exact chemical compositions were measured using X‐ray fluorescence and the densities were determined by Archimedes method and pycnometry. This property and its dependency upon small variations in the composition is the main focus of this paper. The density values were between 2.617 and 2.700 g/cm³ and the packing density factors V p of the oxide glasses using the ionic radii of Pauling ranged from 0.562 to 0.574. The experimentally determined data were compared to different model calculations. Calculations performed according to empirical formulae given in the literature showed relative deviations between −5 and 12% to the experimental values. The effect of MgO was also studied by comparing the glasses with similar compositions (Ceram Int, 2016;42:5810–5822 ) without any MgO.