gebhart/patrepeval huggingface dataset:
Preparation and Mechanical Properties of Polypropylene−Clay Hybrids (1997)

Polypropylene (PP)−clay hybrids (PPCH) have been prepared by simple melt-mixing of three components, i.e., PP, maleic anhydride modified polypropylene oligomers (PP-MA), and clays intercalated with stearylammonium. The dispersibility of 10-Å-thick silicate layers of the clays in the hybrids was investigated by using a transmission electron microscope and X-ray diffractometer. It is found that there are two important factors to achieve the exfoliated and homogeneous dispersion of the layers in the hybrids: (1) the intercalation capability of the oligomers in the layers and (2) the miscibility of the oligomers with PP. Almost complete hybrids were obtained in the case where the PP-MA has both intercalation capability and miscibility. The hybrids exhibit higher storage moduli compared to those of PP especially in the temperature range from Tg to 90 °C. The highest relative storage modulus at 80 °C of the hybrid based on a mica and the miscible PP-MA is as high as 2.0 to that of PP and is 2.4 to that of the PP/PP-MA mixture, which is considered to be the matrix of the PPCH. Also, the effects of the kinds of clays and oligomers on the dynamic moduli are discussed.
α-Synuclein Inclusions in Alzheimer and Lewy Body Diseases (2000)

Alpha-synuclein has assumed particular neuropathological interest in the light both of its identification as a non-beta-amyloid plaque constituent in Alzheimer disease (AD), and the recent association between dominant inheritance of Parkinson disease (PD) and 2 missense mutations at positions 30 and 53 of the synuclein protein. We report a systematic study of alpha-synuclein, tau, and ubiquitin immunoreactivity in representative neurodegenerative disorders of late life. The alpha-synuclein association with Lewy bodies is variable, peripheral, and is not stable with respect to proteases or acid treatment, whereas there is no association with Pick bodies. Stable patterns of immunoreactivity included neurites and a novel inclusion body. Although there is an overlap between the presence of Lewy bodies and stable alpha-synuclein immunoreactivity, this is seen only in the presence of concomitant neuropathological features of AD. The novel alpha-synuclein inclusion body identified in pyramidal cells of the medial temporal lobe in particular was found in AD and in the Lewy body variant of AD, and was associated neither with ubiquitin nor tau protein. The inclusion is therefore neither a Lewy body nor a PHF-core body, but may be confused with the Lewy body, particularly in the Lewy body variant of AD. Abnormal processing of alpha-synuclein leading to its deposition in the form of proteolytically stable deposits is a particular feature of the intermediate stages of AD.
Activation of Marginal Zone B Cells from Lupus Mice with Type A(D) CpG-Oligodeoxynucleotides (2005)

Several types of CpG-oligodeoxynucleotides (ODN) have been recently characterized. In mice, type A(D) CpG-ODNs primarily stimulate macrophages and dendritic cells, but fail to stimulate B cells. On the contrary, type B(K) CpG-ODNs are excellent B cell activators. Type C CpG-ODNs combine features of both types A(D) and B(K) CpG-ODNs. Despite cell type preferences, all CpG-ODNs require the presence of TLR9 for activation. In this study, we show that a subset of B cells from lupus mice responds to type A(D) CpG-ODN stimulation vigorously and directly with increased CD25 and CD86 expression and IL-10 secretion. Furthermore, these CpG-ODNs induce high surface IgM expression and promote 50- to 100-fold higher IgM and IgG3 secretion in lupus B cells than in controls. This response is similar to that seen with bacterial DNA stimulation of B cells. Type A(D)-responsive cells are enriched within lupus B cells with the marginal zone (MZ) phenotype. These cells are at least twice more numerous in lupus mice than in controls. The ability of lupus B cells to respond to type A(D) CpG-ODN stimulation is not due to differential TLR9 expression. Therefore, type A(D) CpG-ODNs may contribute to the lupus pathogenesis by inducing MZ-B cell activation, costimulatory molecule expression, and polyclonal Ig secretion. Through increased IL-10 secretion, MZ-B cells may also modify the activity of other cell types, particularly dendritic cells and macrophages.
Narcissus: visualising information (1999)

It is becoming increasingly important that support is provided for users who are dealing with complex information spaces. The need is driven by the growing number of domains where there is a requirement for users to understand, navigate and manipulate large sets of computer based data; by the increasing size and complexity of this information and by the pressures to use this information efficiently. The paradigmatic example is the World Wide Web, but other domains include software systems, information systems and concurrent engineering. One approach to providing this support is to provide sophisticated visualisation tools which will lead the users to form an intuitive understanding of the structure and behaviour of their domain and which will provide mechanisms which allow them to manipulate objects within their system. This paper describes such a tool and a number of visualisation techniques that it implements. 1 Introduction People are increasingly faced with the problem of filterin...
Tibial nerve stimulation for overactive bladder syndrome unresponsive to medical therapy (2010)

Overactive bladder syndrome is defined as a symptom syndrome which includes urinary urgency, with or without urge incontinence, usually accompanied by frequency (>8 micturitions/24 h) and nocturia. Conservative treatment usually comprises behavioural techniques, bladder retraining, pelvic floor re-education and pharmacotherapy but up to 30% of patients will remain refractory to treatment. Although second-line treatment options such as sacral nerve stimulation and intravesical botulinum A injections are valuable additions to the therapeutic arsenal, they are relatively invasive and can have serious side-effects. Inhibition of detrusor activity by peripheral neuromodulation of the posterior tibial nerve was first described in 1983, with recent authors further confirming a 60-80% positive response rate. This review was undertaken to examine published literature on percutaneous tibial nerve stimulation and to discuss outcome measures, maintenance therapy and prognostic factors of this technique.
Decrease in reactive amino groups during oxidation or endothelial cell modification of LDL. Correlation with changes in receptor-mediated catabolism. (1987)

The monocyte/macrophage appears to be the precursor of many of the lipid-laden cells in atherosclerotic lesions, but the mechanism by which these cells accumulate cholesterol to become foam cells remains unclear. We have previously reported that cultured endothelial cells can modify low density lipoprotein (LDL) in a manner that leads to rapid uptake by the acetyl LDL receptor of macrophages. This modification involves free radical-induced peroxidation of LDL and is accompanied by many changes in the physicochemical properties of LDL including increased electrophoretic mobility, increased density, decreased content of esterified cholesterol, hydrolysis of phosphatidylcholine, and fragmentation of apolipoprotein B. Under conditions highly favorable to oxidation, a similar modification can occur even in the absence of cells. In the present studies, oxidation of LDL simply by exposure to 5 microM Cu++ resulted in a modification that was indistinguishable from that produced by endothelial cells. Moreover, it was demonstrated that LDL oxidation by either method is accompanied by a marked decreased in amino group reactivity, comparable to that seen with the chemical modifications of LDL that lead to recognition by the acetyl LDL receptor. Inhibitors of proteolytic enzymes did not reduce fragmentation of apolipoprotein B during oxidation. The rate of catabolism of intravenously injected oxidized LDL in guinea pigs was very rapid, and over 80% of the degradation occurred in the liver. The studies demonstrate that all of the changes associated with endothelial cell modification of LDL can be attributed to oxidation. The cells can, however, promote oxidation under conditions where it would otherwise occur very slowly.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic Transformation Using Maize Immature Zygotic Embryos (2010)

Epidermal and subepidermal cells in the abaxial, basal region of the maize (Zea mays L.) immature zygotic embryo (IZE) scutellum can be induced by exogenous auxin to proliferate and undergo somatic embryogenesis. Successful genetic transformation of IZEs depends not only on optimizing transformation parameters for these totipotent cells, but also on achieving high embryogenic callus induction frequency (ECIF) in a population of targeted explants. In maize, ECIF is strongly influenced by genotype, the tissue culture media used, and the interaction of these two factors. Altering tissue culture media components to increase ECIF and/or transformation frequency (TF) has been one approach used to expand the range of maize genotypes amenable to genetic transformation using the IZE. This chapter outlines such an approach--an Agrobacterium-mediated transformation protocol is used for direct-targeting IZEs of the hybrid Hi Type II and inbred B104 lines. Two different media regimes are used for successful culture and transformation of two distinct genotypes.
Loss of Spastin Function Results in Disease-Specific Axonal Defects in Human Pluripotent Stem Cell-Based Models of Hereditary Spastic Paraplegia (2013)

Human neuronal models of hereditary spastic paraplegias (HSP) that recapitulate disease-specific axonal pathology hold the key to understanding why certain axons degenerate in patients and to developing therapies. SPG4, the most common form of HSP, is caused by autosomal dominant mutations in the SPAST gene, which encodes the microtubule-severing ATPase spastin. Here, we have generated a human neuronal model of SPG4 by establishing induced pluripotent stem cells (iPSCs) from an SPG4 patient and differentiating these cells into telencephalic glutamatergic neurons. The SPG4 neurons displayed a significant increase in axonal swellings, which stained strongly for mitochondria and tau, indicating the accumulation of axonal transport cargoes. In addition, mitochondrial transport was decreased in SPG4 neurons, revealing that these patient iPSC-derived neurons recapitulate disease-specific axonal phenotypes. Interestingly, spastin protein levels were significantly decreased in SPG4 neurons, supporting a haploinsufficiency mechanism. Furthermore, cortical neurons derived from spastin-knockdown human embryonic stem cells (hESCs) exhibited similar axonal swellings, confirming that the axonal defects can be caused by loss of spastin function. These spastin-knockdown hESCs serve as an additional model for studying HSP. Finally, levels of stabilized acetylated-tubulin were significantly increased in SPG4 neurons. Vinblastine, a microtubule-destabilizing drug, rescued this axonal swelling phenotype in neurons derived from both SPG4 iPSCs and spastin-knockdown hESCs. Thus, this study demonstrates the successful establishment of human pluripotent stem cell-based neuronal models of SPG4, which will be valuable for dissecting the pathogenic cellular mechanisms and screening compounds to rescue the axonal degeneration in HSP.
A Single Mutation in Cytochrome P450 BM3 Changes Substrate Orientation in a Catalytic Intermediate and the Regiospecificity of Hydroxylation (1997)

Phenylalanine 87 of Bacillus megaterium cytochrome P450 BM3, a residue close to the heme in the substrate binding pocket, has been replaced by alanine by site-directed mutagenesis. The substitution had no effect on the rate of hydroxylation of laurate and increased the affinity for laurate of both the intact enzyme and its heme domain by 2.6-6-fold in the ferric state. NMR paramagnetic relaxation measurements showed that in the initial ferric enzyme-substrate complex, where the substrate binds relatively far from the heme, the substitution had no effect on the position or orientation of the bound substrate. However, in the next intermediate in the catalytic cycle, the reduced enzyme, the position of the bound substrate was altered so that the terminal methyl group was 3.1 A from the iron in the mutant, compared to 5.1 A in the wild-type enzyme. Analysis of the products of the action of the enzyme on laurate and myristate showed that the mutant catalyzed hydroxylation almost exclusively at the omega position, in marked contrast to the wild-type enzyme, with which no hydroxylation at this position was observed.
New antibacterial strategies : proceedings of an international symposium sponsored by Glaxo Research, Brocket Hall, Hertfordshire, 30 June-3 July 1990 (1990)

Part 1 Plenary lecture I Bacterial diseases - unsolved problems: Borrelia - the epidemiology of Borrelia burgdorferi infections, Lyme borreliosis - host-parasite interactions, vaccine and antimicrobials, immunodominant proteins of Borrelia burgdorferi - implications for improving serodiagnosis of Lyme borreliosis vaccines - polysaccharide vaccines - vaccines needed for the 1990s, Salmonella vaccines mucosal surface infections - the role of bacterial adherence in urinary tract infections, the pathogenesis of diarrhoea caused by Escherichia coli, pathogenesis of Heliobacter pylori-induced gastroduodenal diseases resistance - the molecular basis of B-lactamase induction in enterobacteria, the molecular basis of quinolone action and resistance, transport systms and their role in drug resistance in bacteria and mammalian cells. Part 2 Plenary lecture II Leprosy - a paradigm for host-microbe interactions: intracellular mechanisms - the intracellular pharmcokinetics and activity of antibiotics, microbial heat-shock protein and autoimmune disease immunomodulatorsm - interleukins and their use as therapeutic agents, the roles of colony-stimulating factors in the treatment of infections.
Crystal Structures of Human MD-2 and Its Complex with Antiendotoxic Lipid IVa (2007)

Endotoxic lipopolysaccharide (LPS) with potent immunostimulatory activity is recognized by the receptor complex of MD-2 and Toll-like receptor 4. Crystal structures of human MD-2 and its complex with the antiendotoxic tetra-acylated lipid A core of LPS have been determined at 2.0 and 2.2 angstrom resolutions, respectively. MD-2 shows a deep hydrophobic cavity sandwiched by two beta sheets, in which four acyl chains of the ligand are fully confined. The phosphorylated glucosamine moieties are located at the entrance to the cavity. These structures suggest that MD-2 plays a principal role in endotoxin recognition and provide a basis for antiseptic drug development.
Bile acids: short and long term effects in the intestine (2010)

Bile acids have secretory, motility and antimicrobial effects in the intestine. In patients with bile acid malabsorption the amount of primary bile acids in the colon is increased compared to healthy controls. Deoxycholic acid is affecting the intestinal smooth muscle activity. Chenodeoxycholic acid has the highest potency to affect intestinal secretion. Litocholic acid has little effect in the lumen of intestine compared to both deoxycholic acid and chenodeoxycholic acid. There is no firm evidence that clinically relevant concentrations of bile acids induce colon cancer. Alterations in bile acid metabolism may be involved in the pathophysiology of constipation.
Identification of two enhancer elements in the gene encoding the type 1 glucose transporter from the mouse which are responsive to serum, growth factor, and oncogenes. (1992)

The type 1 glucose transporter (GLUT1) gene encodes an integral membrane glycoprotein responsible for facilitating transfer of glucose across plasma membrane and is rapidly activated by serum, growth factors, and by oncogenic transformation. To elucidate the molecular mechanisms of regulation of GLUT1 gene expression, we isolated and characterized the mouse GLUT1 gene. DNA elements regulating transcription of the gene were analyzed in transient expression assays after transfection of NIH/3T3 cells with a low background chloramphenicol acetyltransferase (CAT) vector system pSVOOCAT. We identified two enhancer elements; the first one is located 2.7 kilobases upstream of the cap site of the gene which contains the homologous sequences with two 12-O-tetradecanoylphorbol-13-acetate-responsive elements (TREs), a serum response element, a cyclic AMP-responsive element (CRE) and three GC boxes, and the second one is located in the second intron of the gene which contains the homologous sequences with two TREs and one CRE. With the promoter alone the transcription of the gene is activated by src, only slightly activated by ras and is not activated by serum and platelet-derived growth factor. When the gene is accompanied by one of these enhancers, the transcription is activated by all these stimuli.
Clinical Diagnosis of the Dry Eye (1987)

From the Department of Ophthalmology, University of California Medical Center, and the Proctor Foundation, San Francisco, CA.
Emerging and re-emerging viruses of the honey bee (Apis melliferaL.) (2010)

Until the late 1980s, specific viral infections of the honey bee were generally considered harmless in all countries. Then, with the worldwide introduction of the ectoparasite mite Varroa destructor, beekeepers encountered increasing difficulties in maintaining their colonies. Epidemiological surveys and laboratory experiments have demonstrated that the newly acquired virulence of several viruses belonging to the family Dicistroviridae (acute bee paralysis virus, Kashmir bee virus and Israeli acute paralysis virus) in Europe and the USA had been observed in relation with V. destructor acting as a disseminator of these viruses between and within bee colonies and as an activator of virus multiplication in the infected individuals: bee larvae and adults. Equal emphasis is given to deformed wing virus (DWV) belonging to the Iflaviridae. Overt outbreaks of DWV infections have been shown to be linked to the ability of V. destructor to act not only as a mechanical vector of DWV but also as a biological vector. Its replication in mites prior to its vectoring into pupae seemed to be necessary and sufficient for the induction of a overt infection in pupae developing in non-viable bees with deformed wings. DWV in V. destructor infested colonies is now considered as one of the key players of the final collapse. Various approaches for combating bee viral diseases are described: they include selection of tolerant bees, RNA interference and prevention of new pathogen introduction. None of these approaches are expected to lead to enhanced bee-health in the short term.
Discovery of Enzyme Modulators via High-Throughput Time-Resolved FRET in Living Cells (2014)

We have used a "two-color" SERCA (sarco/endoplasmic reticulum calcium ATPase) biosensor and a unique high-throughput fluorescence lifetime plate reader (FLT-PR) to develop a high-precision live-cell assay designed to screen for small molecules that perturb SERCA structure. A SERCA construct, in which red fluorescent protein (RFP) was fused to the N terminus and green fluorescent protein (GFP) to an interior loop, was stably expressed in an HEK cell line that grows in monolayer or suspension. Fluorescence resonance energy transfer (FRET) from GFP to RFP was measured in the FLT-PR, which increases precision 30-fold over intensity-based plate readers without sacrificing throughput. FRET was highly sensitive to known SERCA modulators. We screened a small chemical library and identified 10 compounds that significantly affected two-color SERCA FLT. Three of these compounds reproducibly lowered FRET and inhibited SERCA in a dose-dependent manner. This assay is ready for large-scale HTS campaigns and is adaptable to many other targets.
Suspected Deep Vein Thrombosis (1982)

Controversy exists as to whether patients suspected of having deep vein thrombosis (DVT) can be studied safely without venography, with its attendant expense, inconvenience, and potential risk. We used impedance plethysmography (IPG) in 1,464 consecutive patients suspected of having DVT, with 96% of these patients with normal IPGs, there were no fatal pulmonary emboli (PE). The incidence of nonfatal PE was 1%. In 284 outpatients suspected of having DVT, but discharged without treatment because of normal IPGs, only one patient returned with subsequent symptoms of DVT (0.4%). Noninvasive testing with IPG is a safe and highly cost-effective alternative to venography for routine management of patients suspected of DVT.
Delivering siRNA in vivo for functional genomics and novel therapeutics (2005)

Use of siRNA in vivo to down regulate expression of a specific gene requires knowledge of target sequence accessibility, target tissue deliverability, and, for most applications, siRNA stability in both extracellular and intracellular environments (McManus and Sharp, 2002). Unlike in vitro transfection of siRNA into cells, in vivo delivery of siRNA into targeted tissue of animal models is much more complicated, involving physical, chemical and biological approaches, and in some cases their combination (Lu et al., 2003). A consequence of the fast-growing literature on using siRNA as a research tool for functional genomics is an emerging interest in siRNA as a therapeutic. Therapeutic applications, however, clearly depend upon optimized local and systemic delivery of siRNA in vivo. Therefore, delivering siRNA into targeted tissues and maintaining its activity within targeted cells and on the targeted gene sequence are the key aspects considered here, in order to fulfill the goals of both functional genomic research and therapeutic development.
Quantitative Proteomic Analysis of the Secretory Proteins from Rat Adipose Cells Using a 2D Liquid Chromatography−MS/MS Approach (2005)

We have developed two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) and 18O proteolytic labeling strategies to identify and compare levels of secretory proteins with low abundance in the conditioned medium of rat adipose cells without or with insulin stimulation. Culture medium was concentrated and secreted proteins were separated on a RP-HPLC followed by LC-MS/MS analysis. For 18O proteolytic labeling, 16O- to 18O-exchange in the digested peptides from eight individual fractions was carried out in parallel in H2(16)O and H(2)18O with immobilized trypsin, and the ratios of isotopically distinct peptides were measured by mass spectrometry. A total of 84 proteins was identified as secreted adipokines. This large number of secretory proteins comprise multiple functional categories. Comparative proteomics of 18O proteolytic labeling allows the detection of different levels of many secreted proteins as exemplified here by the difference between basal and insulin treatment of adipose cells. Taken together, our proteomic approach is able to identify and quantify the comprehensive secretory proteome of adipose cells. Thus, our data support the endocrine role of adipose cells in pathophysiological states through the secretion of signaling molecules.
Millimeter‐wave signal generation using semiconductor diode lasers (invited paper) (1993)

Abstract Methods of millimeter‐wave signal generation are presented using frequency multiplication by optical comb generation, direct generation using optical oscillators, and mixing between CW optical sources. © 1993 John Wiley &amp; sons, Inc.
Pelvic Irradiation With Concurrent Chemotherapy Versus Pelvic and Para-Aortic Irradiation for High-Risk Cervical Cancer: An Update of Radiation Therapy Oncology Group Trial (RTOG) 90-01 (2004)

Mature analysis confirms that the addition of fluorouracil and cisplatin to radiotherapy significantly improved the survival rate of women with locally advanced cervical cancer without increasing the rate of late treatment-related side effects.