gebhart/patrepeval huggingface dataset:
Mechanisms of Liver Injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inflammatory conditions (2006)

Polymorphonuclear leukocytes (neutrophils) are a vital part of the innate immune response to microbial infections and tissue trauma, e.g., ischemia-reperfusion injury, in many organs including the liver. However, an excessive inflammatory response can lead to a dramatic aggravation of the existing injury. To design interventions, which selectively target the detrimental effects of neutrophils, a detailed understanding of the pathophysiology is critical. Systemic or local exposure to proinflammatory mediators causes activation and priming of neutrophils for reactive oxygen formation and recruits them into the vascular beds of the liver without causing tissue injury. However, generation of a chemotactic signal from the parenchyma will trigger extravasation and an attack on target cells (e.g., hepatocytes). Adhesion to the target induces degranulation with release of proteases and formation of reactive oxygen species including hydrogen peroxide and hypochlorous acid, which can diffuse into hepatocytes and induce an intracellular oxidant stress and mitochondrial dysfunction. Various neutrophil-derived proteases are involved in transmigration and cell toxicity but can also promote the inflammatory response by processing of proinflammatory mediators. In addition, necrotic cells release mediators, e.g., high-mobility group box-1, which further promotes neutrophilic hepatitis and tissue damage. On the basis of these evolving insights into the mechanisms of neutrophil-mediated liver damage, the most selective strategies appear not to interfere with the cytotoxic potential of neutrophils, but rather strengthen the target cells' defense mechanisms including enhancement of the intracellular antioxidant defense systems, activation of cell survival pathways, or initiation of cell cycle activation and regeneration.
Genome Engineering With Zinc-Finger Nucleases (2011)

Zinc-finger nucleases (ZFNs) are targetable DNA cleavage reagents that have been adopted as gene-targeting tools. ZFN-induced double-strand breaks are subject to cellular DNA repair processes that lead to both targeted mutagenesis and targeted gene replacement at remarkably high frequencies. This article briefly reviews the history of ZFN development and summarizes applications that have been made to genome editing in many different organisms and situations. Considerable progress has been made in methods for deriving zinc-finger sets for new genomic targets, but approaches to design and selection are still being perfected. An issue that needs more attention is the extent to which available mechanisms of double-strand break repair limit the scope and utility of ZFN-initiated events. The bright prospects for future applications of ZFNs, including human gene therapy, are discussed.
Selectin glycoprotein ligands. (2000)

Lectin selectins and their counter-receptors participate in discontinuous cell-cell interactions concurrent with leukocyte tethering and rolling on endothelium, which, in consequence, leads to leukocyte penetration to lymphatic organs and generation of inflammation sites. Counter-receptors are glycoproteins in which carbohydrate units, the direct selectin ligands, are built into the polypeptide framework. In this review, the distribution, structure and function of the main ligands and counter-receptors for P-, L- and E-selectins known so far, have been discussed. The common biosynthetic pathway of sialyl-Lewis x and sulpho-sialyl-Lewis x determinants of selectin ligands has been described.
Use of prostacyclin and its analogues in the treatment of cardiovascular disease. (2002)

Prostacyclin is found in all body tissues and body fluids, and is the major metabolite of arachidonic acid in the vasculature. It is a potent vasodilator that affects both the systemic and pulmonary circulations. Prostacyclin also prevents vascular smooth muscle proliferation and inhibits platelet adhesion and aggregation. These features have made it a very attractive substance for treatment of many different cardiovascular diseases. Epoprostenol, a synthetic prostacyclin, is currently available in parenteral form for the treatment of primary pulmonary hypertension, and has been shown to be a valuable palliative therapy. The drug appears to have limited effectiveness for treating patients with congestive heart failure and coronary artery disease, but has shown some utility in patients with peripheral vascular disease, including Raynaud's phenomenon. Analogues of prostacyclin are now in clinical trials and include iloprost, a stable analogue that has been used intravenously to treat patients with peripheral vascular disease. Other parenteral formulations under investigation include taprostene, ciprostene, and UT-15. Beraprost and cicaprost, are two prostacyclin analogues that can be used in oral form, are being studied in clinical trials.
Spinal anaesthesia for caesarean section: Comparison of maternal and neonatal effects of bolus administration of ephedrine and phenylephrine (2011)

s and Programme: EUROANAESTHESIA 2011: The European Anaesthesiology Congress: Obstetric Anaesthesia
ATRP in Water: Kinetic Analysis of Active and Super-Active Catalysts for Enhanced Polymerization Control (2017)

Atom transfer radical polymerization (ATRP) in water is characterized by very high catalytic activity, i.e. the rate constant (kact) of the “activation” reaction between CuI complexes and alkyl halides (RX) is very large. To accurately study such fast reactions in water, we developed a collection of electrochemical methods applicable for the determination of a vast range of kact values (>7 orders of magnitude). These included rate constants of extremely fast reactions with kact > 107 mol–1 dm3 s–1. We studied three widely used ATRP catalysts ([CuIPMDETA]+, [CuITPMA]+, and [CuIMe6TREN]+) and an extended series of water-soluble initiators. Accurate results were obtained in the range 1 < kact < 108 mol–1 dm3 s–1, allowing to build for the first time precise structure–reactivity correlations for aqueous ATRP, in both pure water and water/monomer mixtures. The results were compared to traditional ATRP systems in organic solvents. The collected data greatly expand the available range of investigated catalyst/initiator systems.
Biochemical analysis of pathogenic ligand-dependent FGFR2 mutations suggests distinct pathophysiological mechanisms for craniofacial and limb abnormalities (2004)

Gain-of-function missense mutations in FGF receptor 2 (FGFR2) are responsible for a variety of craniosynostosis syndromes including Apert syndrome (AS), Pfeiffer syndrome (PS) and Crouzon syndrome (CS). Unlike the majority of FGFR2 mutations, S252W and P253R AS mutations and a D321A PS mutation retain ligand-dependency and are also associated with severe limb pathology. In addition, a recently identified ligand-dependent S252L/A315S double mutation in FGFR2 was shown to cause syndactyly in the absence of craniosynostosis. Here, we analyze the effect of the canonical AS mutations, the D321A PS mutation and the S252L/A315S double mutation on FGFR2 ligand binding affinity and specificity using surface plasmon resonance. Both AS mutations and the D321A PS mutation, but not the S252L/A315S double mutation, increase the binding affinity of FGFR2c to multiple FGFs expressed in the cranial suture. Additionally, all four pathogenic mutations also violate FGFR2c ligand binding specificity and enable this receptor to bind FGF10. Based on our data, we propose that an increase in mutant FGFR2c binding to multiple FGFs results in craniosynostosis, whereas binding of mutant FGFR2c to FGF10 results in severe limb pathology. Structural and biophysical analysis shows that AS mutations in FGFR2b also enhance and violate FGFR2b ligand binding affinity and specificity, respectively. We suggest that elevated AS mutant FGFR2b signaling may account for the dermatological manifestations of AS.
The Soil Microbiome Influences Grapevine-Associated Microbiota (2015)

Vine-associated bacterial communities may play specific roles in the productivity and disease resistance of their host plant. Also, the bacterial communities on grapes have the potential to influence the organoleptic properties of the wine, contributing to a regional terroir. Understanding that factors that influence these bacteria may provide insights into management practices to shape and craft individual wine properties. We show that soil serves as a key source of vine-associated bacteria and that edaphic factors and vineyard-specific properties can influence the native grapevine microbiome preharvest.
Transcribing broadcast news for audio and video indexing (2000)

sources for information dissemination, there is a pressing need for automatic processing of the audio data stream. For the most part, current methods for segmentation, transcription and indexation are manual, with humans reading, listening and watching, annotating topics and selecting items of interest for the user.
An active contour model for mapping the cortex (1995)

A new active contour model for finding and mapping the outer cortex in brain images is developed. A cross-section of the brain cortex is modeled as a ribbon, and a constant speed mapping of its spine is sought. A variational formulation, an associated force balance condition, and a numerical approach are proposed to achieve this goal. The primary difference between this formulation and that of snakes is in the specification of the external force acting on the active contour. A study of the uniqueness and fidelity of solutions is made through convexity and frequency domain analyses, and a criterion for selection of the regularization coefficient is developed. Examples demonstrating the performance of this method on simulated and real data are provided.
The use of computers in teaching clinical laboratory science (1993)

The Transfusion Medicine Tutor (TMT) has been designed to study the use of computers in teaching concepts and problem- solving skills important in the field of clinical laboratory science. This system provides students with an opportunity to gain experience by solving a wide range of actual cases, and coaches these students when they are having difficulties. This system is designed specifically to detect and respond to a variety of errors that students may make while solving cases, and to suggest more advanced problem-solving methods when appropriate. This article describes the concepts behind the design of TMT.
Substance P recognition by a subset of human T lymphocytes. (1984)

The interaction of substance P with human blood T-lymphocytes, which stimulates T-lymphocyte proliferation, was quantified by both flow cytometric and direct binding assays. Fluorescence-detection flow cytometry recorded the binding of dichlorotriazinylamino-fluorescein-labeled substance P to 21 +/- 10% (mean +/- SD, n = 6) and 35 +/- 8% (n = 2) of human blood T-lymphocytes before and after stimulation with 10 micrograms/ml of phytohemagglutinin, respectively. The suppressor-cytotoxic (leu 2a) and helper-inducer (leu 3a) subsets identified by phycoerythrin-labeled monoclonal antibodies contained substance P-reactive T-lymphocytes at respective mean frequencies of 10 and 18%. [3H]substance P bound rapidly and reversibly to a mean of 7035 +/- 2850 sites/T-lymphocyte, which exhibited a dissociation constant (KD) of 1.85 +/- 0.70 X 10(-7) M (mean +/- SD, n = 5). [D-Pro2,D-Phe7,D-Trp9]substance P inhibited the binding of dichlorotriazinylamino-fluorescein-labeled substance P and [3H]substance P to T-lymphocytes at concentrations that suppressed the proliferative response to substance P. Substance P, eledoisin, and substance K (alpha-neurokinin), which all share with substance P the carboxy-terminal substituent -Gly-Leu-Met-NH2, were more potent than substance P in inhibiting the binding of [3H]substance P to T-lymphocytes, suggesting the importance of this sequence in the interaction. Purified human blood B-lymphocytes, monocytes, polymorphonuclear leukocytes, and platelets, and cultured Hut 78 cutaneous lymphoma T-cells, Jurkat cells, Molt-4 lymphoblasts, and HL-60 and U-937 monocyte-like cells all showed only minimal specific binding of [3H]substance P. The recognition of substance P by T-lymphocytes provides one mechanism for selective modulation of immunity by sensory nerves.
Semantic Style Transfer and Turning Two-Bit Doodles into Fine Artworks (2016)

Convolutional neural networks (CNNs) have proven highly effective at image synthesis and style transfer. For most users, however, using them as tools can be a challenging task due to their unpredictable behavior that goes against common intuitions. This paper introduces a novel concept to augment such generative architectures with semantic annotations, either by manually authoring pixel labels or using existing solutions for semantic segmentation. The result is a content-aware generative algorithm that offers meaningful control over the outcome. Thus, we increase the quality of images generated by avoiding common glitches, make the results look significantly more plausible, and extend the functional range of these algorithms---whether for portraits or landscapes, etc. Applications include semantic style transfer and turning doodles with few colors into masterful paintings!
Novel benzothiophene-, benzofuran-, and naphthalenecarboxamidotetrazoles as potential antiallergy agents (1992)

The synthesis and antiallergic activity of a series of novel benzothiophene-, benzofuran-, and naphthalenecarboxamidotetrazoles are described. A number of the compounds inhibit the release of histamine from anti-IgE stimulated basophils obtained from allergic donors. Optimal inhibition is exhibited in benzothiophenes with a 3-alkoxy substituent in combination with a 5-methoxy, 6-methoxy, or a 5,6-dimethoxy group. Compound 13c (CI-959) also inhibited respiratory burst of human neutrophils and the release of mediators from anti-IgE-stimulated human chopped lung.
Accessibility of oxygen with respect to the heme pocket in horseradish peroxidase (2003)

Oxygen and other molecules of similar size take part in a variety of protein reactions. Therefore, it is critical to understand how these small molecules penetrate the protein matrix. The protein system studied in this case is horseradish peroxidase (HRP). We have converted the native HRP into a phosphorescent analog by replacing the heme prosthetic group by Pd-mesoporphyrin. Oxygen readily quenches the phosphorescence of Pd porphyrins, and this can be used to characterize oxygen diffusion through the protein matrix. Our measurements indicate that solvent viscosity and pH modulate the accessibility of the heme pocket relative to small molecules. The binding of the substrate benzohydroxamic acid (BHA) to the protein drastically impedes oxygen access to the heme pocket. These results indicate that, first, the penetration of small molecules through the protein matrix is a function of protein dynamics, and second, there are specific pathways for the diffusion of these molecules. The effect of substrate and pH on protein dynamics has been investigated with the use of molecular dynamics calculations. We demonstrate that the model of a "fluctuating entry point," as suggested by Zwanzig (J Chem Phys 1992;97:3587-3589), properly describes the diffusion of oxygen through the protein matrix.
Advances in the management of cutaneous squamous cell carcinoma (2014)

Cutaneous squamous cell carcinoma is one of the most common non-melanoma skin cancers worldwide. While most cutaneous squamous cell carcinomas are easily managed, there is a high-risk subset of tumors that can cause severe morbidity and mortality. Tumor characteristics as well as patient characteristics contribute to the classification of cutaneous squamous cell carcinomas as low-risk vs. high-risk. Advances in the treatment of cutaneous squamous cell carcinomas largely relate to the management of this high-risk subset. Surgical and non-surgical management options, including newer targeted molecular therapies, will be discussed here. Larger, multicenter studies are needed to determine the exact significance of individual risk factors with respect to aggressive clinical behavior and the risks of metastasis and death, as well as the role of surgical and adjuvant therapies in patients with high-risk cutaneous squamous cell carcinomas.
Gene therapy with herpes simplex virus vectors. (1999)

Gene delivery to the nervous system represents perhaps the ultimate challenge of gene therapy in view of the complexity of this system, the wide variety of intractable neurological diseases and the need to deliver the gene to non-dividing cells. Although a variety of systems for such gene delivery are under development, herpes simplex virus has unique advantages in terms of its large genome size and its ability to enter a latent state in neuronal cells. Considerable progress has been made in the effective disablement of this virus whilst retaining its ability to deliver genes and in producing long term expression of the foreign gene. Although much remains to be achieved in the further disablement of the virus and its testing in rodent and primate models of human diseases, it is likely that these viruses may ultimately be of use in human gene therapy procedures for otherwise intractable neurological diseases.
Nucleic Acid-Based Methods for the Detection of Cancer (1997)

Continued elucidation of the genetic changes that drive cancer progression is yielding new and potentially powerful nucleic acid-based markers of neoplastic disease. Pilot studies indicate that these markers can be used to detect cancer cells in a variety of clinical settings with unprecedented precision. Nucleic acid-based markers may prove to be valuable tools for early detection of cancer in asymptomatic individuals, for confirmation or exclusion of a cancer diagnosis that is based on suspicious but nondiagnostic clinical material, for assessment of tumor burden in cancer patients, and for assessment of response to preventive approaches applied to healthy individuals who are at high risk of developing cancer. Examples of these markers, their potential applications, and the current practical limitations on their clinical use are reviewed here.
Molecular Chaperone-Like Activity of Hydrogel Nanoparticles of Hydrophobized Pullulan:  Thermal Stabilization with Refolding of Carbonic Anhydrase B (1999)

We have been studying the formation of hydrogel nanoparticles by the self-aggregation of hydrophobized polysaccharide and the effective complexation between these nanoparticles as a host and various globular soluble proteins as a guest. This paper describes a new finding that refolding of the heat-denatured enzyme effectively occurs with the nanoparticles and beta-cyclodextrin according to a mechanism similar to that of a molecular chaperone. In particular, the irreversible aggregation of carbonic anhydrase B (CAB) upon heating was completely prevented by complexation between the heat-denatured enzyme and hydrogel nanoparticles formed by the self-aggregation of cholesteryl group-bearing pullulan (CHP). The complexed CAB was released by dissociation of the self-aggregate upon the addition of beta-cyclodextrin. The released CAB refolded to the native form, and almost 100% recovery of the activity was achieved. The thermal stability of CAB was drastically improved by capture of the unfolded form which was then released to undergo refolding.
Classification of malignant pediatric renal tumors by gene expression (2006)

Classifiers based on gene expression provide diagnostic confidence and accuracy greater than that of pathologic analysis alone. Tumors that show ambiguous gene expression profiles are those that are also pathologically and molecularly ambiguous and merit further analysis.
PRIDE: The proteomics identifications database (vol. 5, Issue 13, pp. 3537‐3545) (2005)

Abstract See original http://dx.doi.org/10.1002/pmic.200401303
Scaling of advanced power systems (1991)

Parts of a study conducted to examine state-of-the-art power systems applicable to future military spacecraft are summarized. The study focused on burst-mode megawatt-class CW power, such as might be applied to SDIO directed energy systems, but lower-power, continuous-duty subsystems were included in less detail. A set of simple mass and volume algorithms has been developed to approximate several prime systems, and these were incorporated into a Lotus 1-2-3 spreadsheet. Among the power subsystems included in that study were primary batteries, alkaline primary fuel cells, and combustion turbogenerators. These systems, which are the most likely candidates for mobile battlefield power, are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Synthesis of α-Amino Isocyanides and α-Alkylthio Isocyanides (1993)

α-Morpholinobenzyl isocyanide and three 1-(aryl[or alkyl]thio)alkyl isocyanides are synthesized in good yields by the dehydration of N-(α-morpholinobenzyl)formamide and N-[1-(alkylthio)alkyl]formamides, themselves prepared from 1-(1-formylaminoalkyl)benzotriazoles with morpholine or with thiols.
Neuroleptics of the diphenylbutylpiperidine series are potent calcium channel inhibitors. (1986)

[3H]Fluspirilene, a neuroleptic molecule of the diphenylbutylpiperidine series, binds to skeletal muscle transverse tubule membranes with a high affinity corresponding to a Kd of 0.11 +/- 0.04 nM, A 1:1 stoichiometry was found between [3H]fluspirilene binding and the binding of (-)-[3H]desmethoxyverapamil [(-)[3H]D888], one of the most potent Ca2+ channel inhibitors. Ca2+ channel inhibitors such as D888, verapamil, gallopamil, bepridil, or diltiazem antagonize [3H]fluspirilene binding besides antagonizing (-)[3H]-D888 binding. Neuroleptics, especially those of the diphenylbutylpiperidine family, also antagonize both (-)[3H]D888 binding and [3H]fluspirilene binding. There is an excellent correlation between affinities found from [3H]fluspirilene binding experiments and those found from (-)[3H]D888 binding experiments. Analysis of the properties of these cross-inhibitions indicates that [3H]fluspirilene binds to a site that is not identical to that for phenylalkylamine derivatives (gallopamil, verapamil, diltiazem, and bepridil). Voltage-clamp experiments have shown that fluspirilene is an efficient inhibitor of the voltage dependent Ca2+ channel, achieving a half-maximal effect near 0.1-0.2 nM and nearly complete blockade at 1 nM. Fluspirilene blockade has little voltage dependence.
Polymorphism of 1,3,5‐Trinitrobenzene Induced by a Trisindane Additive (2004)

The most stable is not necessarily the most easy to obtain! Two new stable crystal forms of the 120 year old compound sym-trinitrobenzene are reported. These elusive forms have been obtained by the use of an additive, trisindane, that can act as a mimic in the crystallization experiment (see scheme). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z52253_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.