gebhart/patrepeval huggingface dataset:
Kinetic mechanism of Escherichia coli isocitrate dehydrogenase and its inhibition by glyoxylate and oxaloacetate (1986)

The inhibition of Escherichia coli isocitrate dehydrogenase by glyoxylate and oxaloacetate was examined. The shapes of the progress curves in the presence of the inhibitors depended on the order of addition of the assay components. When isocitrate dehydrogenase or NADP+ was added last, the rate slowly decreased until a new, inhibited, steady state was obtained. When isocitrate was added last, the initial rate was almost zero, but the rate increased slowly until the same steady-state value was obtained. Glyoxylate and oxaloacetate gave competitive inhibition against isocitrate and uncompetitive inhibition against NADP+. Product-inhibition studies showed that isocitrate dehydrogenase obeys a compulsory-order mechanism, with coenzyme binding first. Glyoxylate and oxaloacetate bind to and dissociate from isocitrate dehydrogenase slowly. These observations can account for the shapes of the progress curves observed in the presence of the inhibitors. Condensation of glyoxylate and oxaloacetate produced an extremely potent inhibitor of isocitrate dehydrogenase. Analysis of the reaction by h.p.l.c. showed that this correlated with the formation of oxalomalate. This compound decomposed spontaneously in assay mixtures, giving 4-hydroxy-2-oxoglutarate, which was a much less potent inhibitor of the enzyme. Oxalomalate inhibited isocitrate dehydrogenase competitively with respect to isocitrate and was a very poor substrate for the enzyme. The data suggest that the inhibition of isocitrate dehydrogenase by glyoxylate and oxaloacetate is not physiologically significant.
A Major Fraction of Endoplasmic Reticulum-located Glutathione Is Present as Mixed Disulfides with Protein (2004)

The tripeptide glutathione is the most abundant thiol/disulfide component of the eukaryotic cell and is known to be present in the endoplasmic reticulum lumen. Accordingly, the thiol/disulfide redox status of the endoplasmic reticulum lumen is defined by the status of glutathione, and it has been assumed that reduced and oxidized glutathione form the principal redox buffer. We have determined the distribution of glutathione between different chemical states in rat liver microsomes by labeling with the thiol-specific label monobromobimane and subsequent separation by reversed phase high performance liquid chromatography. More than half of the microsomal glutathione was found to be present in mixed disulfides with protein, the remainder being distributed between the reduced and oxidized forms of glutathione in the ratio of 3:1. The high proportion of the total population of glutathione that was found to be in mixed disulfides with protein has significant implications for the redox state and buffering capacity of the endoplasmic reticulum and, hence, for the formation of disulfide bonds in vivo.
A Simple Conversion of Alcohols into Amines (1987)

In a convenient one-pot sequence, treatment of alcohols and α-hydroxyesters with hydrazoic acid, di-isopropyl azodicarboxylate and an excess of triphenylphosphine in tetrahydrofuran, followed by addition of water or aqueous acid, yields amines or amino-acid esters in moderate to good overall yields.
Monodisperse Double Emulsions Generated from a Microcapillary Device (2005)

Double emulsions are highly structured fluids consisting of emulsion drops that contain smaller droplets inside. Although double emulsions are potentially of commercial value, traditional fabrication by means of two emulsification steps leads to very ill-controlled structuring. Using a microcapillary device, we fabricated double emulsions that contained a single internal droplet in a core-shell geometry. We show that the droplet size can be quantitatively predicted from the flow profiles of the fluids. The double emulsions were used to generate encapsulation structures by manipulating the properties of the fluid that makes up the shell. The high degree of control afforded by this method and the completely separate fluid streams make this a flexible and promising technique.
Identification of a Novel Cytokine, ML-1, and Its Expression in Subjects with Asthma (2001)

A novel gene, designated ML-1, was identified from a human genomic DNA clone and human T cell cDNA sequences. The second exon of ML-1 gene shares significant sequence identity with the gene encoding IL-17 (IL-17). ML-1 gene expression was up-regulated in activated PBMCs, CD4(+) T cells, allergen-specific Th0, Th1, and Th2 clones, activated basophils, and mast cells. Increased expression of the ML-1 gene, but not IL-17, was seen following allergen challenge in four asthmatic subjects, suggesting its role in allergic inflammatory responses. ML-1 from transiently transfected COS-7 cells was able to induce gene expression and protein production for IL-6 and IL-8 (at 10 ng/ml of ML-1: for IL-6, 599.6 +/- 19.1 pg/ml; for IL-8, 1724.2 +/- 132.9 pg/ml; and at 100 ng/ml of ML-1: for IL-6, 1005.3 +/- 55.6 pg/ml; for IL-8, 4371.4 +/- 280.5 pg/ml; p < 0.05 for both doses vs baseline) in primary bronchial epithelial (PBE) cells. Furthermore, increased expression of ICAM-1 was found in ML-1-stimulated PBE cells (mean fluorescence intensity (MFI) = 31.42 +/- 4.39 vs baseline, MFI = 12.26 +/- 1.77, p < 0.05), a functional feature distinct from IL-17 (MFI = 11.07 +/- 1.22). This effect was not inhibited by a saturating amount of IL-17. These findings demonstrate that ML-1 is a novel cytokine with a distinct function, and suggest a different receptor for ML-1 on PBE cells.
Cyclization-activated Prodrugs (2007)

Many drugs suffer from an extensive first-pass metabolism leading to drug inactivation and/or production of toxic metabolites, which makes them attractive targets for prodrug design. The classical prodrug approach, which involves enzyme-sensitive covalent linkage between the parent drug and a carrier moiety, is a well established strategy to overcome bioavailability/toxicity issues. However, the development of prodrugs that can regenerate the parent drug through non-enzymatic pathways has emerged as an alternative approach in which prodrug activation is not influenced by inter- and intraindividual variability that affects enzymatic activity. Cyclization-activated prodrugs have been capturing the attention of medicinal chemists since the middle-1980s, and reached maturity in prodrug design in the late 1990 s. Many different strategies have been exploited in recent years concerning the development of intramoleculary-activated prodrugs spanning from analgesics to anti-HIV therapeutic agents. Intramolecular pathways have also a key role in two-step prodrug activation, where an initial enzymatic cleavage step is followed by a cyclization-elimination reaction that releases the active drug. This work is a brief overview of research on cyclization-activated prodrugs from the last two decades.
Evaluation by Fluorescence Resonance Energy Transfer of the Stability of Nonviral Gene Delivery Vectors under Physiological Conditions (2002)

The stability in physiological medium of polyplex- and lipoplex-type nonviral gene vectors was evaluated by detecting the conformational change of complexed plasmid DNA (pDNA) labeled simultaneously with fluorescein (energy donor) and X-rhodamine (energy acceptor) through fluorescence resonance energy transfer (FRET). Upon mixing with cationic components, such as LipofectAMINE, poly(L-lysine), and poly(ethylene glycol)-poly(L-lysine) block copolymer (PEG-PLys), the fluorescence spectrum of doubly labeled pDNA underwent a drastic change due to the occurrence of FRET between the donor-acceptor pair on pDNA taking a globular conformation (condensed state) through complexation. The measurement was carried out also in the presence of 20% serum, under which conditions FRET from condensed pDNA was clearly monitored without interference from coexisting components in the medium, allowing evaluation of the condensed state of pDNA in nonviral gene vectors under physiological conditions. Serum addition immediately induced a sharp decrease in FRET for the LipofectAMINE/pDNA (lipoplex) system, which was consistent with the sharp decrease in the transfection efficiency of the lipoplex system in serum-containing medium. In contrast, the PEG-PLys/pDNA polyplex (polyion complex micelle) system maintained appreciable transfection efficiency even in serum-containing medium, and FRET efficiency remained constant for up to 12 h, indicating the high stability of the polyion complex micelle under physiological conditions.
Domain adaptation for large-scale sentiment classification: A deep learning approach (2011)

The exponential increase in the availability of online reviews and recommendations makes sentiment classification an interesting topic in academic and industrial research. Reviews can span so many different domains that it is difficult to gather annotated training data for all of them. Hence, this paper studies the problem of domain adaptation for sentiment classifiers, hereby a system is trained on labeled reviews from one source domain but is meant to be deployed on another. We propose a deep learning approach which learns to extract a meaningful representation for each review in an unsupervised fashion. Sentiment classifiers trained with this high-level feature representation clearly outperform state-of-the-art methods on a benchmark composed of reviews of 4 types of Amazon products. Furthermore, this method scales well and allowed us to successfully perform domain adaptation on a larger industrial-strength dataset of 22 domains. 1.
Assessment of systolic and diastolic ventricular properties via pressure-volume analysis: a guide for clinical, translational, and basic researchers (2005)

Assessment of left ventricular systolic and diastolic pump properties is fundamental to advancing the understanding of cardiovascular pathophysiology and therapeutics, especially for heart failure. The use of end-systolic and end-diastolic pressure-volume relationships derived from measurements of instantaneous left ventricular pressure-volume loops emerged in the 1970s as a comprehensive approach for this purpose. As invasive and noninvasive techniques for measuring ventricular volume improved over the past decades, these relations have become commonly used by basic, translational, and clinical researchers. This review summarizes 1) the basic concepts underlying pressure-volume analysis of ventricular and myocardial systolic and diastolic properties, 2) deviations from ideal conditions typically encountered in real-life applications, 3) how these relationships are appropriately analyzed, including statistical analyses, and 4) the most common problems encountered by investigators and the appropriate remedies. The goal is to provide practical information and simple guidelines for accurate application and interpretation of pressure-volume data as they pertain to characterization of ventricular and myocardial properties in health and disease.
Short-Term Exposure to Membrane-Active Antibiotics Inhibits Cryptosporidium parvum Infection in Cell Culture (2000)

A cell culture system and double fluorogenic staining were used to study the susceptibility of Cryptosporidium parvum to membrane-active antibiotics. Buforin II and magainin II exerted a cytotoxic effect on sporozoites but did not consistently affect oocyst viability. Lasalocid and nigericin demonstrated less activity against sporozoites but reduced the infectivity of oocysts.
COMPLETE SUPPRESSION OF SKIN ALLOGRAFT REJECTION IN RATS TREATED WITH CONTINUOUS INFUSION OF 2ʼDEOXYCOFORMYCIN (1985)

Congenital deficiency of the enzyme adenosine deaminase (ADA) results in severe combined immunodeficiency. 2'deoxycoformycin (2'dcf) is a tightly binding inhibitor of ADA, and the drug makes it possible to mimic a state of ADA deficiency. In this study we tested the immunosuppressive effect of 2'dcf in a rat skin transplantation model. Rats treated with continuous infusion of 2'dcf at doses of 0.3 mg/kg, 0.5 mg/kg and 0.7 mg/kg body wt/day showed significant prolongation of graft survival. 2'dcf given by bolus injections did not prolong graft survival. In rats treated with continuous infusion of 2'dcf at a dose of 0.7 mg/kg body wt/day mean graft survival time (MST) after withdrawal of treatment was equal to MST in untreated animals, suggesting that during 2'dcf treatment allograft rejection was completely suppressed. In vitro, lymphocytes isolated from animals treated with continuous infusion of 2'dcf showed marked suppression of mitogen response. The 2'dcf preferentially effects lymphocytes, but neutrophils seem resistant to the effect of the drug. The lymphocytotoxic effect of the drug is extreme; during therapy splenic weight decreased by almost 50% and the differential lymphocyte count in blood decreased from 85% to 17%. Immunofluorescence studies showed that, within the spleen, the amount of T cells and B cells decreased markedly. Both T cell subsets were affected--OX8+ cells (suppressor/cytotoxic T cells) and W3/25+ (helper T cells). However OX8+ cells were more resistant to the drug than W3/25+ cells. Skin-grafted rats treated with 2'dcf showed a strong decrease in the W3/25: OX8 ratio. In contrast, untreated rats showed a slight increase in the ratio after skin transplantation. It is concluded that 2'dcf is a strong immunosuppressive drug in rats if given by continuous infusion.
Nanoscale Microelectrochemical Cells on Carbon Nanotubes (2007)

Nanoscale microelectrochemical cells can form on individual carbon nanotubes in neutral aqueous solutions of KMnO4, leading to corrosion of the nanotubes (see image) and simultaneous deposition of nanocrystalline MnO2 on both external and internal surfaces of the nanotubes.
CHAIN ROTATIONAL DYNAMICS IN MR SUSPENSIONS (2002)

The dynamics of induced dipolar chains in magnetorhelogical suspensions subject to rotating magnetic fields has been experimentally studied combining scattering dichroism and video microscopy experiments. When a rotating field is imposed the chainlike aggregates rotate synchronously with the magnetic field. We found that the average size of the aggregates decreases with Mason number (ratio of viscous to magnetic forces) following a power law with exponent -0.5 being the hydrodynamic friction forces the cause of the chains break up. However the total number of aggregated particles shows two different behaviors depending on Mason number. For low Mason numbers, the total number of aggregated particles remains almost constant and above a critical Mason number, the rotation of the field prevents the particle aggregation process from taking place so the number of aggregated particles decreases with Mason number following a power law behavior with exponent -1. Athermal molecular dynamics simulations are also reported, showing good agreement with the experiments.
Effect of Keigai-Rengyo-To, a Japanese Kampo Medicine, on Neutrophil Functions: A Possible Mechanism of Action of Keigai-Rengyo-To in Acne (1997)

On the basis of recent reports that keigai-rengyo-to (TJ-50), an oral Japanese Kampo (herb) medicine, is clinically effective in treating acne, and that tetracyclines are effective against acne by acting directly as an antioxidant on infiltrated neutrophils, we investigated the effect of TJ-50 on the generation of reactive oxygen species (ROS), using human neutrophils and a cell-free, xanthine-xanthine oxidase system. The species investigated were superoxide radical anion (O2-), hydrogen peroxide (H2O2), and hydroxyl radical (OH.). In addition, neutrophil chemotaxis, phagocytosis and calcium concentration, [Ca2+]i in neutrophils were also assessed. TJ-50 significantly decreased neutrophil-generated O2-, H2O2 and OH. in a dose-dependent manner. Three kinds of ROS generated in the cell-free system were also reduced in the presence of TJ-50. On the other hand, the medicine did not markedly affect neutrophil chemotaxis, phagocytosis or [Ca2+]i in neutrophils. Our results indicate that the clinical effectiveness of TJ-50 in the treatment of acne may be due partly to its antioxidant action on infiltrated neutrophils.
Do We Know When, What and For How Long to Treat? (2012)

Community-acquired pneumonia (CAP) is a common cause of morbidity among children in developed countries and accounts for an incidence of 10-40 cases per 1000 children in the first 5 years of life. Given the clinical, social and economic importance of CAP, there is general agreement that prompt and adequate therapy is essential to reduce the impact of the disease. The aim of this discussion paper is to consider critically the available data concerning the treatment of uncomplicated pediatric CAP and to consider when, how and for how long it should be treated. This review has identified the various reasons that make it difficult to establish a rational approach to the treatment of pediatric CAP, including the definition of CAP, the absence of a pediatric CAP severity score, the difficulty of identifying the etiology, limited pharmacokinetic (PK)/pharmacodynamic (PD) studies, the high resistance of the most frequent respiratory pathogens to the most widely used anti-infectious agents and the lack of information concerning the changes in CAP epidemiology following the introduction of new vaccines against respiratory pathogens. More research is clearly required in various areas, such as the etiology of CAP and the reasons for its complications, the better definition of first- and second-line antibiotic therapies (including the doses and duration of parenteral and oral antibiotic treatment), the role of antiviral treatment and on how to follow-up patients with CAP. Finally, further efforts are needed to increase vaccination coverage against respiratory pathogens and to conduct prospective studies of their impact.
Epitranscriptomics: A New Regulatory Mechanism of Brain Development and Function (2018)

Epigenetic modifications of DNA and chromatin are long known to control stem cell differentiation and organ function but the role of similar modifications at the level or regulatory RNAs is just beginning to emerge. Over 160 RNA modifications have been identified but their abundance, distribution and functional significance are not known. The few available maps of RNA modifications indicated their dynamic regulation during somatic stem cell differentiation, brain development and function in adulthood suggesting a hitherto unsuspected layer of regulation both at the level of RNA metabolism and post-transcriptional control of gene expression. The advent of programmable, RNA-specific CRISPR-Cas editing platforms together with the identification of RNA modifying enzymes now offers the opportunity to investigate the functional role of these elusive epitranscriptome changes. Here, we discuss recent insights in studying the most abundant modifications in functional mRNAs and lncRNAs, N6-methyladenosine and 5-(hydroxy-)methylcytosine, and their role in regulating somatic stem cell differentiation with particular attention to neural stem cells during mammalian corticogenesis. An outlook on novel CRISPR-Cas based systems that allow stem cell reprogramming by epitranscriptome-editing will also be discussed.
Use of 1,1-Dimethylhydrazine in the Atomic Layer Deposition of Transition Metal Nitride Thin Films (2000)

Atomic layer deposition (ALD) of TiN, , NbN, and thin films from the corresponding metal chlorides and 1,1 ‐dimethylhydrazine (DMHy) was studied. Generally, the films deposited at 400°C exhibited better characteristics compared to the films deposited at the same temperature using as the nitrogen source. In addition, films could be deposited at lower temperatures down to 200°C. Even though the carbon content in the films was quite high, in the range of 10 atom %, the results encourage further studies. Especially the effect of carbon on the barrier properties and the use of other possibly less carbon‐contaminating hydrazine derivatives should be studied. © 2000 The Electrochemical Society. All rights reserved.
Efficient generation of polarization-entangled photons in a nonlinear crystal (2006)

We review the use of bidirectional pumping and collinear propagation in type-II phase-matched periodically poled KTiOPO4 to achieve efficient generation of polarization-entangled photons via spontaneous parametric downconversion. The advantages of this approach are fully exploited in our optimized polarization Sagnac interferometric source. Its measured flux of 4700 polarization-entangled photon pairs/s per milliwatt of pump power in a 1-nm bandwidth exhibited 99% quantum-interference visibility. We also present a plane-wave Gaussian state theory for continuous-wave spontaneous parametric downconversion. This formulation affords the complete description of multiple-pair emissions that is needed for quantum communication analyses while reducing to the usual biphoton-state description at low generation rates.
Effects of Human Growth Hormone on Haematopoietic Recovery of Rats Receiving Chemotherapy (2008)

Human growth hormone (hGH) is a pleiotropic cytokine targeting a variety of tissues. Its protective effects on haematopoiesis during treatment with chemotherapeutic drugs were investigated. Sprague-Dawley rats were intraperitoneally administered with both carboplatin and 5-fluorouracil together with or without recombinant hGH (rhGH) at a dose of 1 IU/kg/day. Body weight, full blood count, bone marrow differential count and expression of proliferating cell nuclear antigen (PCNA) in bone marrow were measured weekly for 4 weeks in chemotherapy-treated (CT) or chemotherapy plus rhGH-treated (CT+GH) animals. During the first week, body weight, white blood cell count, haematopoietic count and reticulocyte count were decreased in the CT group as well as in the CT+GH group, but to a lesser extent in the latter group (CT vs. CT+GH group, p < 0.05). Further decreases were also prevented in the CT+GH group. Myeloid cells were extremely hypoplastic in the CT group, while in the CT+GH group, myeloid cells recovered from obviously hypoplastic to excessively hyperplastic in the first 2 weeks, and the myeloid karyocyte count increased significantly (CT+GH vs. CT group, p < 0.05). PCNA-positive cell count in the CT+GH group was also significantly higher than in the CT group (CT+GH vs. CT group, p < 0.05). Thus, rhGH showed a promising protective effect on body weight loss and haematopoietic recovery of chemotherapy-treated rats, which may be useful in clinic to reduce the side effects of chemotherapy.
Proteomics Reveals Age-Related Differences in the Host Immune Response to Sepsis (2013)

Sepsis is commonly caused by community-acquired pneumonia (CAP) and may develop into severe sepsis, characterized by multiple organ failure. The risk of severe sepsis among CAP patients and subsequent mortality increases sharply after the age of 65. The molecular mechanisms associated with this age-related risk are not fully understood. To better understand factors involved with increased incidence and mortality of severe sepsis in the elderly, we used a nested case-control study of patients enrolled in a multicenter observational cohort of 2320 participants with CAP. We identified a total of 39 CAP patients 50-65 and 70-85 years old who did or did not develop severe sepsis. Plasma samples were obtained on presentation to the emergency department and prior to therapeutic interventions. A semiquantitative plasma proteomics workflow was applied which incorporated tandem immunoaffinity depletion, iTRAQ labeling, strong cation exchange fractionation, and nanoflow liquid chromatography coupled to high-resolution mass spectrometry. In total, 772 proteins were identified, of which 58 proteins exhibit statistically significant differences in expression levels among patients with severe sepsis as a function of age. Differentially expressed proteins are involved in pathways such as acute phase response, coagulation signaling, atherosclerosis signaling, lipid metabolism, and production of nitric oxide and reactive oxygen species. This study provides insight into factors that may explain age-related differences in incidence of severe sepsis in the elderly.