gebhart/patrepeval huggingface dataset:
Synthesis and Evaluation of Fatty Acid Amides on the <i>N</i>-Oleoylethanolamide-Like Activation of Peroxisome Proliferator Activated Receptor α (2015)

A series of fatty acid amides were synthesized and their peroxisome proliferator-activated receptor α (PPAR-α) agonistic activities were evaluated in a normal rat liver cell line, clone 9. The mRNAs of the PPAR-α downstream genes, carnitine-palmitoyltransferase-1 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) as PPAR-α agonistic activities. We prepared nine oleic acid amides. Their PPAR-α agonistic activities were, in decreasing order, N-oleoylhistamine (OLHA), N-oleoylglycine, Oleamide, N-oleoyltyramine, N-oleoylsertonin, and Olvanil. The highest activity was found with OLHA. We prepared and evaluated nine N-acylhistamines (N-acyl-HAs). Of these, OLHA, C16:0-HA, and C18:1Δ(9)-trans-HA showed similar activity. Activity due to the different chain length of the saturated fatty acid peaked at C16:0-HA. The PPAR-α antagonist, GW6471, inhibited the induction of the PPAR-α downstream genes by OLHA and N-oleoylethanolamide (OEA). These data suggest that N-acyl-HAs could be considered new PPAR-α agonists.
Invariant Natural Killer T Cell Subsets—More Than Just Developmental Intermediates (2018)

Invariant natural killer T (iNKT) cells are a CD1d-restricted T cell population that can respond to lipid antigenic stimulation within minutes by secreting a wide variety of cytokines. This broad functional scope has placed iNKT cells at the frontlines of many kinds of immune responses. Although the diverse functional capacities of iNKT cells have long been acknowledged, only recently have distinct iNKT cell subsets, each with a marked functional predisposition, been appreciated. Furthermore, the subsets can frequently occupy distinct niches in different tissues and sometimes establish long-term tissue residency where they can impact homeostasis and respond quickly when they sense perturbations. In this review, we discuss the developmental origins of the iNKT cell subsets, their localization patterns, and detail what is known about how different subsets specifically influence their surroundings in conditions of steady and diseased states.
Sources of Leukocytic Endogenous Mediator in the Rat (1973)

After stimulation in vivo with heat-killed Staphylococcus aureus, rat peritoneal granulocytes and macrophages produced leukocytic endogenous mediator (LEM). When this LEM was injected into normal rats, it lowered plasma iron and zinc concentrations and markedly increased blood neutrophils. Incubation of macrophages. blood leukocytes, or Kupffer cells with S. aureus in tissue culture media and rat plasma in vitro gave low yields of LEM. Further evidence was presented to show that serum taken from rats 4 hr after an ip injection of Diplococcus pneumoniae contained LEM.
Alteration of the expression of the hypocretin (orexin) gene by 2-deoxyglucose in the rat lateral hypothalamic area (2000)

Following an i.p. injection of 2-deoxyglucose (2DG), a nonmetabolizable analogue of glucose known to induce intracellular glucopenia, a progressive decrease in the level of hypocretin (Hcrt)/orexin mRNA was observed in the rat lateral hypothalamus while the melanin-concentrating hormone (MCH) expression in neighbouring neurons remained unaffected. This result together with the previously reported stimulation of Hcrt expression by insulin confirms that Hcrt neurons, but not MCH neurons, are sensitive to glucose availability and suggests that they respond through different mechanisms and/or different pathways to intracellular glucopenia and hypoglycemic conditions.
Investigation of peptide thioester formation via N→Se acyl transfer (2013)

Native chemical ligation is widely used for the convergent synthesis of proteins. The peptide thioesters required for this process can be challenging to produce, particularly when using Fmoc-based solid-phase peptide synthesis. We have previously reported a route to peptide thioesters, following Fmoc solid-phase peptide synthesis, via an N→S acyl shift that is initiated by the presence of a C-terminal cysteine residue, under mildly acidic conditions. Under typical reaction conditions, we occasionally observed significant thioester hydrolysis as a consequence of long reaction times (~48 h) and sought to accelerate the reaction. Here, we present a faster route to peptide thioesters, by replacing the C-terminal cysteine residue with selenocysteine and initiating thioester formation via an N→Se acyl shift. This modification allows thioester formation to take place at lower temperatures and on shorter time scales. We also demonstrate how application of this strategy also accelerates peptide cyclization, when a linear precursor is furnished with an N-terminal cysteine and C-terminal selenocysteine.
Biochemical and Morphological Effects of Human Hepatic Alkaline Phosphatase in a Neonate with Hypophosphatasia (1989)

Enzyme replacement-therapy for a severely affected premature boy (birthweight: 2,380 g, GA: 36 weeks) with hypophosphatasia was attempted by infusions of purified human hepatic alkaline phosphatase. Treatment (1.2 IU/kg/min) started at age three weeks and was repeated in weekly intervals until age 10 weeks, when the child died. Samples of alkaline phosphatase were diluted with 10 ml of physiological saline and infused over 30 min via an umbilical arterial catheter. No toxic or allergic side effects were observed. Serum alkaline phosphatase activity increased from 3 IU/L before treatment to a maximum level of 195 IU/L with a half-life time between 37 and 62 hours. Urinary excretion of phosphoethanolamine decreased during therapy from a maximal level of 9.5 to 5.5 mumol/mg creatinine (normal: less than 0.4 mumol/mg creatinine). Calcium, phosphorus, parathormone and 1,25-diOH vitamin D levels were within normal range. Sequential radiographic studies showed no improvement of bone mineralization. Bone morphology was studied by light and electron microscopy before treatment and post mortem. The borderline between mineralized and unmineralized matrix was more distinct after treatment and on the electron microscopical level initial spots of mineralization were more frequent between the collagen fibrils compared to the biopsy specimen before treatment. In contrast to previous studies however, only woven and bundle bone structures were studied from the tibial crest, where the lack of osteoblast-like cells upon the newly formed osteoid matrix was prominent.
Heparin-induced Thrombocytopenia: Clinical Considerations of Alternative Anticoagulation with Various Glycosaminoglycans and Thrombin Inhibitors (1999)

Heparin-induced thrombocytopenia (HIT), the most common complication of heparin therapy, is also the most common form of the drug-induced thrombocytopenias. HIT is classified as type I and type II, the first being benign and the latter severe. HIT type II is attributed to an immune response characterized by complexes of heparin and platelet factor (PF) 4. Enzyme-linked immunosorbent assays allow easy and simple determination of these antibody titers; however, because specificity and sensitivity is not optimal, there is concern that the clinical relevance may be low. In clinical trials many patients were shown to form HIT-IgG in response to heparin without developing manifestations of HIT type II. Therefore, routine screening of clinically asymptomatic patients for antiheparin/PF 4 antibodies is not recommended. HIT type II is a clinico-pathologic syndrome that ideally should be confirmed by laboratory testing. If any clinical suspicion arises, however, heparin and low molecular weight heparin therapy should be discontinued and an alternative anticoagulant therapy started. Alternative drugs have been evaluated in significant numbers of patients including danaparoid and thrombin inhibitors. In the case of danaparoid, it is highly recommended that an in vitro test for cross-reactivity be performed before the onset of therapy. If testing cannot be performed, immediate administration of a thrombin inhibitor is preferred.
Free-space grating multi/demultiplexer and wavelength-router for densely spaced WDM networks (1997)

Densely spaced wavelength division multiplexed (WDM) networks using wavelength routing are considered to be potential candidates for the next generation wavelength routed optical networks. Very small channel spacing ( 0.8 nm) in these networks will require high resolution demultiplexers transparent to modulation formats, combined with a high rejection of adjacent channels to ensure a low level of crosstalk. Whilst a low-loss and crosstalk free-space concave grating demultiplexer has been demonstrated, this article describes its transmission spectra using standard single mode optical fibre inputs and outputs and measured by three different high resolution techniques. The impact of grating aberrations and defocusing on demultiplexer transmission spectra are also discussed. We also demonstrate the wavelength channel drop in the double optical pass free-space grating router with single mode fibre input/outputs. (5 pages)
The Biologic Effects of C225, A Chimeric Monoclonal Antibody to the EGFR, on Human Prostate Carcinoma (1996)

For prostate cancer, a correlation exists between overexpression of the epidermal growth factor receptor (EGFR) and poor clinical prognosis. In addition, late-stage metastatic disease is characterized by a change from a paracrine to an autocrine mode of expression for TGF-alpha, the ligand for the EGFR. These observations suggest that activation of the EGFR may be important for the growth of prostatic carcinoma in situ, and blockade of the receptor-ligand interaction may offer a means of therapeutic intervention for this disease. We describe the biologic effects of a chimeric anti-EGFR monoclonal antibody, C225, on several human prostate tumor cell lines in culture and the tumor inhibitory properties of the antibody for the treatment of human prostate carcinoma xenografts in nude mice. In vitro analysis of the EGFR from androgen-responsive and independent prostatic carcinoma cell lines revealed that C225 blocked EGF-induced receptor activation and induced internalization of the receptor. In vivo, a treatment regimen of C225 alone or antibody plus doxorubicin significantly inhibited tumor progression of well-established DU145 and PC-3 xenografts in nude mice. These results suggest that C225 may have utility for the treatment of human prostate carcinoma in a clinical setting.
Next Generation Web Search: Setting Our Sites. (2000)

The current state of web search is most successful at directing users to appropriate web sites. Once at the site, the user has a choice of following hyperlinks or using site search, but the latter is notoriously problematic. One solution is to develop specialized search interfaces that explicitly support the types of tasks users perform using the information specific to the site. A new way to support task-based site search is to dynamically present appropriate metadata that organizes the search results and suggests what to look at next, as a personalized intermixing of search and hypertext. 1
Geometric and Error Analysis for 3D Map-Matching (2009)

Three dimensional maps have recently made their way into mass production and are becoming a common feature in in-car navigation systems as well as in mobile phones. 3D and photorealistic navigation provides a variety of new applications through photorealistic and textured 3D city models and navigable maps. For mapmatching purposes, monocular vision can be used for image capture, feature extraction and description. Images captured with monocular vision can be used in real-time for matching 2D images with the photorealistic 3D model. Detecting, extracting and describing features for 3D matching purposes will aid INS and GNSS signal tracking, providing a seamless navigation solution for dense urban areas. The aim of this paper is to outline the error sources and geometric constraints of 3D map matching based on the reconstructed 3D model. The objectives of this paper are to integrate positioning data with digital road network data so that vehicles can have accurate positioning solutions across different environments, especially in urban canyons. Map matching characteristics are described through discussions on geometric limitations, and a variety of error sources and their propagation. To address the positioning challenge under urban environments, the quality of the visual measurements, the technical details concerning 3D maps and the use of measurements made by integrating GPS/INS and vision for positioning are presented. A matching process, where a photo-realistic 3D map in the database is matched with an image or images captured in real-time is a proposed solution by the authors to enhance navigation in dense urban areas.
The assessment of antiangiogenic and antivascular therapies in early-stage clinical trials using magnetic resonance imaging: issues and recommendations (2005)

Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.
Tissue Receptor for Cholera Exotoxin: Postulated Structure from Studies with G M1 Ganglioside and Related Glycolipids (1973)

By a double-diffusion precipitation-in-gel technique, isolated cholera toxin as well as its natural toxoid were shown to be fixed and precipitated by the ganglioside G(M1) but not by any of the related glycolipids G(M3), G(M2), G(M1)-GlcNAc, G(D1a), G(D1b), G(T1), globoside, G(A1), and tetrahexoside-GlcNAc. Twenty-five nanograms of G(M1) was enough to give a precipitation line with 1.2 mug of toxin, whereas about 50 ng was required with this amount of toxoid. G(M1) also inactivated the toxin in the ileal loop as well as in the intradermal models in rabbits. A 1: 1 molar ratio of ganglioside to toxin was found limiting, e.g., 100 pg of G(M1) could inactivate 5 ng (about 50 blueing doses) of isolated toxin. G(M1) inactivated crude toxin (culture fil rate) with the same efficiency as isolated toxin, and the inactivating capacity of G(M1) was unaffected by mixing with other gangliosides, indicating the specificity in the reaction between G(M1) and toxin. The other glycolipids tested did not inactivate toxin except G(D1a) and G(A1) which did so with approximately 1,000 times less efficiency than G(M1). This identified the portion Gal --> GalNAc [Formula: see text] as the critical region in G(M1) for toxin fixation, and it is postulated that this may be the tissue receptor structure for the cholera toxin.
Interactive simulation and comparative visualisation of the bone-determined range of motion of the human shoulder. (2006)

Pre-operative planning systems aid clinicians by giving insight into patient-specific issues before surgery is performed. The ability to perform a virtual shoulder replacement procedure enables the surgeon to explore the probable and plausible outcomes. Pre-operative planning software assists the surgeon in this complex decision-making
Visualization and Manipulation of Plasma Membrane-Endoplasmic Reticulum Contact Sites Indicates the Presence of Additional Molecular Components within the STIM1-Orai1 Complex (2007)

STIM1, a recently identified endoplasmic reticulum (ER) protein, rapidly translocates to a plasma membrane-adjacent ER compartment upon depletion of the ER Ca(2+) stores. Here we use a novel means, namely a chemically inducible bridge formation between the plasma and ER membranes, to highlight the plasma membrane-adjacent ER compartment and show that this is the site where STIM1 and its Ca(2+) channel partner, Orai1, form a productive interaction upon store depletion. By changing the length of the linkers connecting the plasma and ER membranes, we show that Orai1 requires a larger space than STIM1 between the two membranes. This finding suggests that Orai1 is part of a larger macromolecular cluster with an estimated 11-14-nm protrusion to the cytoplasm, whereas the cytoplasmic domain of STIM1 fits in a space calculated to be less than 6 nm. We finally show that agonist-induced translocation of STIM1 is rapidly reversible and only partially affects STIM1 in the juxtanuclear ER compartment. These studies are the first to detect juxtaposed areas between the ER and the plasma membrane in live cells, revealing novel details of STIM1-Orai1 interactions.
Cache decay: exploiting generational behavior to reduce cache leakage power (2002)

Power dissipation is increasingly important in CPUs ranging from those intended for mobile use, all the way up to high performance processors for high-end servers. While the bulk of the power dissipated is dynamic switching power leakage power is also beginning to be a concern. Chipmakers expect that in future chip generations, leakage's proportion of total chip power will increase significantly. This paper examines methods for reducing leakage power within the cache memories of the CPU. Because caches comprise much of a CPU chip's area and transistor counts, they are reasonable targets for attacking leakage. We discuss policies and implementations for reducing cache leakage by invalidating and "turning off" cache lines when they hold data not likely to be reused. In particular our approach is targeted at the generational nature of cache line usage. That is, cache lines typically have a flurry of frequent use when first brought into the cache, and then have a period of "dead time" before they are evicted. By devising effective, low-power ways of deducing dead time, our results show that in many cases we can reduce Ll cache leakage energy by 4/spl times/ in SPEC2000 applications without impacting performance. Because our decay-based techniques have notions of competitive on-line algorithms at their roots, their energy usage can be theoretically bounded at within a factor of two of the optimal oracle-based policy. We also examine adaptive decay-based policies that make energy-minimizing policy choices on a per-application basis by choosing appropriate decay intervals individually, for each cache line. Our proposed adaptive policies effectively reduce Ll cache leakage energy by 5/spl times/ for the SPEC2000 with only negligible degradations in performance.
Temperature‐Induced Changes in the Dynamic Rheological Behavior and Size Distribution of Polymeric Proteins for Glutens from Wheat Near‐Isogenic Lines Differing in HMW Glutenin Subunit Composition (2000)

ABSTRACT Viscoelasticity of hydrated gluten depends on composition of HMW gluten subunits (GS), size distribution of glutenin polymers, and proteinprotein interactions. Glutens extracted from four near‐isogenic lines with differing HMW‐GS were analyzed. Rheological properties were studied by dynamic assay in shear. Size distribution of prolamins was determined by sequential extraction and size‐exclusion HPLC. Assays performed at 20°C confirmed that viscoelasticity was determined by large glutenin polymers. The abundance of large glutenin polymers depended on the HMW‐GS composition of the lines. Difference of functionality linked to subunit structure was highlighted by comparing the behaviors of the 1A/1B null and 1A/1D null lines. Glutens were submitted to heating and cooling cycles, with or without an SH‐blocking agent (N‐ethylmaleimide [NEMI]). At 20–40°C, no irreversible changes of the mechanical properties occurred. Thermal treatment affected chain mobility, and possibly H bonds, but not the chemical structure of the network. At &gt;40°C, irreversible rheological changes were observed without NEMI. Irreversibility was mainly due to chemical modifications affecting the polymer size distribution through SH‐SS exchange reactions. The sensitivity of gluten to temperature depended on subunit composition.
Direct Observation of the Ferromagnetic Spin Polarization in Gold Nanoparticles: A Review (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Aflibercept in the Treatment of Metastatic Colorectal Cancer (2012)

Colorectal cancer is the third most common cancer in the US. In recent decades, an improved understanding of the role of the angiogenesis pathway in colorectal cancer has led to advancements in treatment. Bevacizumab has been shown to improve the progression-free survival and overall survival when combined with cytotoxic chemotherapy in patients with metastatic colorectal cancer, and at present is the only antiangiogenesis agent approved for the treatment of this cancer. Aflibercept is a novel angiogenesis-targeting agent, and has demonstrated efficacy in treating metastatic colorectal cancer in a recent randomized Phase III trial. Here we review the role of angiogenesis in the tumorigenesis of colorectal cancer, strategies for targeting angiogenesis, and the clinical development of aflibercept.
A 16-channel 8-parameter waveform electrotactile stimulation system (1991)

We have developed a general-purpose electrotactile (electrocutaneous) stimulation system as a research tool for studying psychophysiological performance associated with various stimulation waveforms. An experimenter-defined command file specifies the stimulation current and waveform of each of the 16 channels. The system provides burst onset delay of 0-20 ms, phase current of 0-50 mA, interphase interval of 0-1000 microseconds, number of pulses per burst from 1-100, pulse repetition rate of 0.1-25 kHz, phase width of 2-1000 microseconds, and functionally-monophasic pulses (with zero dc current) or balanced-biphasic pulses (with equal positive and negative phases). The system automatically delivers the desired stimulation, prompts the subject for responses, and then logs subject responses. Key features of the system are 1) very flexible choice of bursts of pulsatile waveforms, 2) real-time control of all of the waveform parameters as mathematical functions of external analog inputs, and 3) high-performance electrode-driver circuitry.
Hypochlorous acid regulates neutrophil extracellular trap release in humans (2011)

Neutrophil extracellular traps (NETs) comprise extracellular chromatin and granule protein complexes that immobilize and kill bacteria. NET release represents a recently discovered, novel anti-microbial strategy regulated non-exclusively by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase generation of reactive oxygen intermediates (ROIs), particularly hydrogen peroxide. This study aimed to characterize the role of ROIs in the process of NET release and to identify the dominant ROI trigger. We employed various enzymes, inhibitors and ROIs to record their effect fluorometrically on in vitro NET release by human peripheral blood neutrophils. Treatment with exogenous superoxide dismutase (SOD) supported the established link between hydrogen peroxide and NET production. However, treatment with myeloperoxidase inhibitors and direct addition of hypochlorous acid (HOCl; generated in situ from sodium hypochlorite) established that HOCl was a necessary and sufficient ROI for NET release. This was confirmed by the ability of HOCl to stimulate NET release in chronic granulomatous disease (CGD) patient neutrophils which, due to the lack of a functional NADPH oxidase, also lack the capacity for NET release in response to classical stimuli. Moreover, the exogenous addition of taurine, abundantly present within the neutrophil cytosol, abrogated NET production stimulated by phorbol myristate acetate (PMA) and HOCl, providing a novel mode of cytoprotection by taurine against oxidative stress by taurine.
Compromised GCF total antioxidant capacity in periodontitis: cause or effect? (2006)

Local total antioxidant capacity in CP appears to reflect increased oxygen radical activity during periodontal inflammation and can be restored to control subject levels by successful non-surgical therapy.