gebhart/patrepeval huggingface dataset:
Neuroendocrine Regulation of Skin Dendritic Cells (2006)

It has long been postulated that stress can affect certain skin conditions, and there is increasing experimental evidence that the neuroendocrine system can directly participate in cutaneous inflammation. Neurohormones, such as glucocorticoids and catecholamines, can reach the skin through the bloodstream after activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, respectively. Multiple neuropeptides, among them calcitonin gene-related peptide, alpha-melanocyte stimulating hormone, pituitary adenylate cyclase-activating peptide, substance P, vasoactive intestinal peptide, and norepinephrine, may be released by cutaneous nerves or resident and infiltrating cells within the skin. Systemic neuromediators and cutaneous nerves can influence a number of target cells within the skin, among them Langerhans cells. Most of the experimental evidence to date indicates a suppressive effect of the neurohormones and neuropeptides on Langerhans cell function and cutaneous inflammation, but it has become evident lately that the timing of exposure to a stimulus is critical to the outcome of the immune response. Thus, administration of a stress hormone or exposure to a stressor before the dendritic cell (DC) encounters an antigen (Ag) may diminish the immune response toward that Ag, while a stressor may enhance immune function when acting on a maturing DC or before reexposure to the Ag. The neuroendocrine regulation of skin DCs is a complex system allowing for a quick adaptation to various stressors. Such a system, originally evolved to defend the organism against invading pathogens and maintain homeostasis, may under certain conditions become unbalanced and ultimately exacerbate cutaneous inflammation.
Structural and Dynamic Features of Bis[2-(2-furyl)indenyl]zirconium Derivatives (2001)

Treatment of 2-indanone with 2-lithio-5-methylfuran, followed by hydrolysis, dehydration, deprotonation with n-butyllithium, and transmetalation, gave bis[2-(5-methyl-2-furyl)indenyl]zirconium dichloride (6a). The dynamic 600 MHz 1H NMR spectroscopic analysis in the temperature range between 253 and 128 K revealed the presence of two metallocene conformational isomers in a 60:40 ratio. It is likely that this observed feature just originates from freezing out the indenyl−furyl rotation. The corresponding activation barrier of 6a was determined at ΔG⧧rot = 7.0 ± 0.4 kcal mol-1 by a line shape analysis. A series of analogous 5-methyl-2-furyl- and 5-methyl-2-thienyl-substituted bis(indenyl)zirconium dibromides and dichlorides show analogous conformational behavior and almost identical rotational activation energies. In the bis[2-(5-methyl-2-furyl)indenyl]ZrR2 series the metallocene rotational barrier can apparently be frozen on the 600 MHz 1H NMR time scale for R = CH2CMe3 and R = CH2Ph. The di(neopentyl)Zr complex 7b shows a metallocene rotational barrier of ΔG⧧rot(Cp)(213 K) = 9.0 ± 0.3 kcal mol-1, and for the di(benzyl)Zr complex 7c a ΔG⧧rot(Cp) value of 11.4 ± 0.3 kcal mol-1 was obtained at 243 K. In the cases of 7b and 7c only chiral rac-type metallocene conformers were found in solution within the limits of the accuracy of the 1H NMR method. The complexes bis[2-(5-ethyl-2-furyl)indenyl]ZrCl2 (8) and bis[2-(5-methyl-2-furyl)indenyl]Zr(neopentyl)2 (7b) were characterized by X-ray crystal structure analyses. In the solid state both complexes exhibit chiral rac-like metallocene frameworks.
ARB: a software environment for sequence data (2004)

The ARB (from Latin arbor, tree) project was initiated almost 10 years ago. The ARB program package comprises a variety of directly interacting software tools for sequence database maintenance and analysis which are controlled by a common graphical user interface. Although it was initially designed for ribosomal RNA data, it can be used for any nucleic and amino acid sequence data as well. A central database contains processed (aligned) primary structure data. Any additional descriptive data can be stored in database fields assigned to the individual sequences or linked via local or worldwide networks. A phylogenetic tree visualized in the main window can be used for data access and visualization. The package comprises additional tools for data import and export, sequence alignment, primary and secondary structure editing, profile and filter calculation, phylogenetic analyses, specific hybridization probe design and evaluation and other components for data analysis. Currently, the package is used by numerous working groups worldwide.
Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases (2015)

Myeloperoxidase (MPO) is a heme peroxidase that catalyzes the production of hypochlorous acid. Clinical evidence suggests a causal role for MPO in various autoimmune and inflammatory disorders including vasculitis and cardiovascular and Parkinson's diseases, implying that MPO inhibitors may represent a therapeutic treatment option. Herein, we present the design, synthesis, and preclinical evaluation of N1-substituted-6-arylthiouracils as potent and selective inhibitors of MPO. Inhibition proceeded in a time-dependent manner by a covalent, irreversible mechanism, which was dependent upon MPO catalysis, consistent with mechanism-based inactivation. N1-Substituted-6-arylthiouracils exhibited low partition ratios and high selectivity for MPO over thyroid peroxidase and cytochrome P450 isoforms. N1-Substituted-6-arylthiouracils also demonstrated inhibition of MPO activity in lipopolysaccharide-stimulated human whole blood. Robust inhibition of plasma MPO activity was demonstrated with the lead compound 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999, 8) upon oral administration to lipopolysaccharide-treated cynomolgus monkeys. On the basis of its pharmacological and pharmacokinetic profile, PF-06282999 has been advanced to first-in-human pharmacokinetic and safety studies.
Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines (2008)

CD4(+)CD25(high)FoxP3(+) regulatory T (Treg) cells limit antigen-specific immune responses and are a cause of suppressed anticancer immunity. In preclinical and clinical studies, we assessed the immune consequences of FoxP3(+) Treg-cell depletion in patients with advanced malignancies. We demonstrated that a CD25(high) targeting immunotoxin (denileukin diftitox) depleted FoxP3(+) Treg cells, decreased Treg-cell function, and enhanced antigen-specific T-cell responses in vitro. We then attempted to enhance antitumor immune responses in patients with carcinoembryonic antigen (CEA)-expressing malignancies by Treg-cell depletion. In a pilot study (n = 15), denileukin diftitox, given as a single dose or repeated dosing, was followed by immunizations with dendritic cells modified with the fowlpox vector rF-CEA(6D)-TRICOM. By flow cytometric analysis, we report the first direct evidence that circulating CD4(+)CD25(high)FoxP3(+) Treg cells are depleted after multiple doses of denileukin diftitox. Earlier induction of, and overall greater exposure to, the T-cell response to CEA was observed in the multiple-dose group, but not the single-dose group. These results indicate the potential for combining Treg-cell depletion with anticancer vaccines to enhance tumor antigen-specific immune responses and the need to explore dose and schedule of Treg depletion strategies in optimizing vaccine efforts.
The development of bispecific antibodies and their applications in tumor immune escape (2017)

During the past two decades, a great evolution of bispecific antibodies (BsAbs) for therapeutic applications has been made. BsAbs can bind simultaneously two different antigens or epitopes, which leads to a wide range of applications including redirecting T cells or NK cells to tumor cells, blocking two different signaling pathways, dual targeting of different disease mediators, and delivering payloads to targeted sites. Aside from approved catumaxomab (anti-CD3 and anti-EpCAM) and blinatumomab (anti-CD3 and anti-CD19), many more BsAbs are now in various phases of clinical development. Here, this review focus on the development of bispecific antibodies and their applications in tumor immune escape.
IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis (1991)

Resistance to Leishmania major in mice is associated with the generation of distinct CD4+ Th subsets, termed TH1 and TH2. To define the factors contributing to the genesis of these Th cells, we first investigated when these subsets developed following L. major infection. Lymph node (LN) cells collected 3 days after infection of BALB/c mice secreted IL-4 and IL-5 in vitro, but little IFN-gamma, whereas LN cells from a resistant strain, C3H/HeN, secreted IFN-gamma and no IL-4 or IL-5. Cytokine production was eliminated in both cases by in vivo or in vitro depletion of CD4+ cells, but not after depletion of CD8+ cells. Similar responses were observed after inoculation of killed promastigotes or a soluble leishmanial Ag preparation. These data indicate that the development of Th1- and Th2-like responses can precede lesion formation and does not require a live infection. We next investigated whether IFN-gamma was important in the differentiation of Th1 and Th2 cells. C3H/HeN mice have previously been shown to be susceptible to leishmanial infection after treatment with anti-IFN-gamma. We confirmed this observation and found that the abrogation of resistance was associated with enhanced production of IL-4 and IL-5, and decreased production of IFN-gamma by cells taken from these mice. Conversely, LN cells from BALB/c mice inoculated with parasites plus IFN-gamma produced significantly higher levels of IFN-gamma, and decreased levels of IL-4 and IL-5, than mice infected with parasites alone. Finally, we determined if IFN-gamma might augment vaccine induced immunity. We found that s.c. immunization with soluble leishmanial Ag, the bacterial adjuvant, Corynebacterium parvum and IFN-gamma could protect mice against L. major infection, and that this protection was associated with induction of Th1 responses. From these data we conclude that levels of IFN-gamma at the time of infection or immunization dramatically alters the type of response elicited: high levels of IFN-gamma favor Th1 type responses, whereas low levels promote a Th2 response.
Guidebook to the extracellular matrix, anchor, and adhesion proteins (1999)

This new edition of Guidebook to the Extracellular Matrix and Adhesion Proteins brings up-to-date information on the purification, activities, antibodies and genes for the proteins found in the extracellular matrix and those known to be involved in cell-cell contact and adhesion. Since the first edition much has been learned on the structure of these proteins and their diverse roles in cell communication and metabolite exchange. The Sambrook and Tooze guidebooks provide succinct and up-to-date information on particular classes of important biological molecules, accompanied by short bibliographies, which enable both specialists and newcomers to the field to gain access to unfamiliar work. Drawing on a wide range of sources, this volume addresses all aspects of the structure and function of modules in the extracellular matrix, adhesion molecules, cell adhesion and cell-cell contact proteins. This book is intended for postgraduate and professional researchers in biochemistry and cell biology. Biomedical scientists whose research encompasses this field will also find this book useful.
Inhibitory Effect of Diethyl Pyrocarbonate on the H+/Organic Cation Antiport System in Rat Renal Brush-border Membranes (1989)

We examined the effect of diethyl pyrocarbonate (DEPC), a histidine-specific reagent, on the H+/organic cation antiport system in brush-border membrane vesicles isolated from the rat renal cortex. Pretreatment of membrane vesicles with DEPC resulted in the inhibition of tetraethylammonium transport. This inhibition was reversed by subsequent treatment with hydroxylamine, but not with dithiotreitol. In contrast, the uptake of p-aminohippurate, a typical organic anion, was not inhibited by DEPC pretreatment. In the absence of an H+ gradient, pretreatment with DEPC inhibited the uptake of tetraethylammonium at pH 6.0-7.0, but not at pH 7.5. The Vmax value of tetraethylammonium uptake at pH 7.0 was decreased without any change in the Km value, but the kinetic parameters at pH 7.5 were unchanged. Unlabeled tetraethylamonium did not protect against the inhibition by DEPC. These results suggest that histidine residues in the organic cation carrier are essential for transport at acidic and neutral pH values, but not at alkaline pH values, and that histidine residues play an important role as regulatory sites in the H+/organic cation antiport system rather than as binding sites for organic cations.
Rapid prototyping of microfluidic devices with integrated wrinkled gold micro-/nano textured electrodes for electrochemical analysis (2015)

Fully-integrated electro-fluidic systems with micro-/nano-scale features have a wide range of applications in lab-on-a-chip systems used for biosensing, biological sample processing, and environmental monitoring. Rapid prototyping of application-specific electro-fluidic systems is envisioned to facilitate the testing, validation, and market translation of several lab-on-a-chip systems. Towards this goal, we developed a rapid prototyping process for creating wrinkled micro-/nano-textured electrodes on shrink memory polymers, fabricating microfluidics using molds patterned by a craft-cutter, and bonding electrical and fluidic circuitries using a PDMS partial curing method optimized for creating void-free bonds at the side walls and surfaces of tall (>5 μm) micro-/nano-textured wrinkled electrodes. The resulting electro-fluidic devices, featuring closely spaced high topography electrodes for electrochemical analysis, can withstand flow-rates and burst pressures larger than 25 mL min(-1) and 125 kPa, respectively. In addition, the fully-integrated electrochemical flow-cell developed here demonstrates excellent electrochemical behaviour, with negligible scan to scan variation for over 100 cyclic voltammetry scans, and expected redox signatures measured under various voltage scan rates and fluidic flow rates.
Surface-tension-driven microactuation based on continuous electrowetting (2000)

This paper describes the first microelectromechanical systems (MEMS) demonstration device that adopts surface tension as the driving force. A liquid-metal droplet can be driven in an electrolyte-filled capillary by locally modifying the surface tension with electric potential. We explore this so-called continuous electrowetting phenomenon for MEMS and present crucial design and fabrication technology that reduce the surface-tension-driving principle, inherently powerful in microscale, into practice. The key issues that are identified and investigated include the problem of material compatibility, electrode polarization, and electrolysis, as well as the micromachining process. Based on the results from the initial test devices and the design concept for a long-range movement of the liquid-metal droplet, we demonstrate a liquid micromotor, an electrolyte and liquid-metal droplets rotating along a microchannel loop. Smooth and wear-free rotation of the liquid system is shown at a speed of /spl sim/40 mm/s (or 420 r/min along a 2-mm loop) with a driving voltage of only 2.8 V and little power consumption (10-100 /spl mu/W).
Efficient Routes to Pyrazolo[3,4-b]indoles and Pyrazolo[1,5-a]benzimidazoles via Palladium- and Copper-Catalyzed Intramolecular C−C and C−N Bond Formation (2009)

Efficient synthetic routes to pyrazolo[3,4-b]indoles and pyrazolo[1,5-a]benzimidazoles via intramolecular palladium- and copper-catalyzed cyclization of 1-aryl/1-unsubstituted 5-(2-bromoanilino)pyrazole precursors via intramolecular C-C and C-N bond formation have been reported.
Steps in the conversion of .alpha.-ketosuberate to 7-mercaptoheptanoic acid in methanogenic bacteria (1989)

The biosynthetic steps involved in the conversion of alpha-ketosuberate to 7-mercaptoheptanoic acid were studied in cell-free extracts of methanogenic bacteria. The pathway was established by measuring the incorporation of stable isotopically labeled precursors into the S-methyl ether methyl ester derivative of the enzymatically generated 7-mercaptoheptanoic acid by using gas chromatography-mass spectrometry (GC-MS). Quantitation of the 7-mercaptoheptanoic acid produced in the incubations with the substrates was accomplished by using an internal standard of 6-mercaptohexanoic acid. [4,4,6,6-2H4]-2-Oxosuberic acid, [7-2H]-7-oxoheptanoic acid, [2-2H]-2(RS)-(5-carboxypentyl)thiazolidine-4(R)-carboxylic acid, and S-(6-carboxyhexyl)cysteine were each shown to be converted to 7-mercaptoheptanoic acid. Incubation of cell extracts with a mixture of 2(RS)-(5-carboxypentyl)thiazolidine-4(R)-carboxylic acid and [2-2H]-2-(RS)-(5-carboxypentyl)-[34S]thiazolidine-4(R)-carboxylic acid showed that both 34S and 2H are incorporated into the 7-mercaptoheptanoic acid but only after separation of the cysteine from the [7-2H]-7-oxyheptanoic acid portion of the molecule. Furthermore, the sulfur from the cysteine was incorporated into the thiol only after its elimination from the cysteine and subsequent mixing with an unlabeled sulfur source which had a molecular weight of sufficient size that it was excluded from Sephadex G-25. Hydrogen sulfide was found to supply the sulfur for the production of the 7-mercaptoheptanoic acid in a reaction that was shown to obtain its reducing equivalents from hydrogen via an F420-dependent hydrogenase.
Mesoscopic Quantum Optics (1999)

Basic Concepts. Canonical Quantization. Quantum States of the Electromagnetic Fields. Coherence of the Electromagnetic Fields. Quantum States of Atoms. Interaction between Atoms and Fields. Mathematical Methods for System-Reservoir Interaction. Stochastic Wavefunction Methods. Quantum Nondemolition Measurements. Semiconductor Bloch Equations. Excitons and Polaritons. Coulomb Blockade and Squeezing. Current Noise in Mesoscopic and Macroscopic Conductors. Nonequilibrium Green's Function Formalism. Quantum Statistical Properties of a Laser. Index.
Improved Electrical Performance of MILC Poly-Si TFTs Using $\hbox{CF}_{4}$ Plasma by Etching Surface of Channel (2009)

In this letter, a new manufacturing method for metal-induced lateral crystallization (MILC) polycrystalline silicon thin-film transistors (poly-Si TFTs) using CF <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> plasma was proposed. It was found that CF <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> plasma effectively minimizes the trap-state density by etching away the top surface of MILC and passivating the trap states, leading to superior electrical characteristics such as high field-effect mobility, low threshold voltage, low subthreshold slope, low leakage current, and high ON-/ OFF-current ratio. CF <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> -plasma MILC TFTs also possess high immunity against the hot-carrier stress and thereby exhibit better reliability than that of conventional MILC TFTs. Moreover, the manufacturing processes are simple (without any additional thermal annealing step) and compatible with MILC TFT processes.
Phase II study of gemcitabine in patients with advanced hepatocellular carcinoma (2000)

Gemcitabine shows marginal antitumor activity in patients with advanced HCC, although the response duration is short-lived. Gemcitabine seems to be particularly promising because of its low toxicity profile. Further studies in combination with other active agents are warranted.
Expression and secretion of heterologous proteases by Corynebacterium glutamicum (1995)

Genes encoding the basic protease of Dichelobacter nodosus (bprV) and the subtilisin of Bacillus subtilis (aprE) were cloned and expressed in Corynebacterium glutamicum. In each case, enzymatically active protein was detected in the supernatants of liquid cultures. While the secretion of subtilisin was directed by its own signal peptide, the natural signal peptide of the bprV basic protease did not facilitate secretion. A hybrid aprE-bprV gene in which the promoter and signal peptide coding sequences of subtilisin replaced those of bprV could be expressed, and basic protease was secreted by C. glutamicum. Expression of these proteases in C. glutamicum provides an opportunity to compare protein secretion from this gram-positive host with that from other gram-positive and gram-negative bacteria.
Novel Hydrophobically Modified Asymmetric RNAi Compounds (sd-rxRNA) Demonstrate Robust Efficacy in the Eye (2013)

These data support the potential of developing sd-rxRNAs as a therapeutic for ocular disease.
Ciliary neurotrophic factor maintains the pluripotentiality of embryonic stem cells (1993)

Ciliary neurotrophic factor was discovered based on its ability to support the survival of ciliary neurons, and is now known to act on a variety of neuronal and glial populations. Two distant relatives of ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M, mimic ciliary neurotrophic factor with respect to its actions on cells of the nervous system. In contrast to ciliary neurotrophic factor, leukemia inhibitory factor and oncostatin M also display a broad array of actions on cells outside of the nervous system. The overlapping activities of leukemia inhibitory factor, oncostatin M and ciliary neurotrophic factor can be attributed to shared receptor components. The specificity of ciliary neurotrophic factor for cells of the nervous system results from the restricted expression of the alpha component of the ciliary neurotrophic factor receptor complex, which is required to convert a functional leukemia inhibitory factor/oncostatin M receptor complex into a ciliary neurotrophic factor receptor complex. The recent observation that the alpha component of the ciliary neurotrophic factor receptor complex is expressed by very early neuronal precursors suggested that ciliary neurotrophic factor may act on even earlier precursors, particularly on cells previously thought to be targets for leukemia inhibitory factor action. Here we show the first example of ciliary neurotrophic factor responsiveness in cells residing outside of the nervous system by demonstrating that embryonic stem cells express a functional ciliary neurotrophic factor receptor complex, and that ciliary neurotrophic factor is similar to leukemia inhibitory factor in its ability to maintain the pluripotentiality of these cells.
A Factor VII Concentrate for Therapeutic Use (1980)

A concentrate of factor VII suitable for therapeutic use has been prepared from human plasma by a method forming part of a comprehensive scheme of large-scale plasma fractionation. Factor VIII was separated as cryoprecipitate and factors II, IX and X were adsorbed on DEAE-cellulose. Most of the factor VII remained in the supernatant. By batch adsorption on DEAE-Sepharose, followed by elution on a chromatographic column, factor VII was concentrated about 25-fold, and purified about 50-fold compared with original plasma, without the need for further dialysis or concentration steps. Data are presented from 10 batches, each from 80-120 kg plasma. Following doses of factor VII to six congenitally deficient patients, the mean rise in plasma factor VII was 95-100% of theoretical; the half-disappearance time was about 4 h. The treatment of four patients with acquired deficiency of factor VII is also described. No untoward side effects were observed.