gebhart/patrepeval huggingface dataset:
Molecular basis for Glanzmann's thrombasthenia (GT) in a compound heterozygote with glycoprotein IIb gene: a proposal for the classification of GT based on the biosynthetic pathway of glycoprotein IIb-IIIa complex (1992)

The genetic basis for Glanzmann's thrombasthenia (GT) was elucidated on a compound heterozygote with glycoprotein (GP)IIb gene: an opal mutation at the end of exon 17 (CGA----TGA) results in only a trace amount of GPIIb mRNA, and a splicing mutation at the acceptor site of exon 26 (CAG----GAG) causes an in-frame, exon skipping process from exon 25 to 27. This aberrant transcript encodes a single-chain polypeptide characterized by a 42-amino acid deletion, which includes the proteolytic cleavage site(s) and a unique, proline-rich region at the location corresponding to the carboxyl-terminal of the normal GPIIb alpha-chain. These characteristics are shared by a previously reported defective GPIIb molecule, which is neither assembled with GPIIIa nor transported to the cellular surface. Despite its normal transcription level, expression of the present defective GPIIb molecule was significantly decreased (approximately 6% of the control level). Because the precursor GPIIb molecule is assembled with GPIIIa in the endoplasmic reticulum (ER) and its processing, as well as stability, is dependent on the GPIIIa subunit, the defective GPIIb molecule may be rapidly degraded by the intrinsic quality control system of the ER due to its inability to form a stable heterodimer complex as a consequence of its misfolded structure. Although we did not confirm that the GPIIIa genes of this individual were normal, GPIIIa may be secondarily decreased (approximately 11% of control), because a large part of it could not be complexed, making it vulnerable to proteolysis. To elucidate the molecular basis for GT, we propose here a classification of GT based on the biosynthetic pathway of the GPIIb-IIIa complex.
Convexity, Classification, and Risk Bounds (2006)

Many of the classification algorithms developed in the machine learning literature, including the support vector machine and boosting, can be viewed as minimum contrast methods that minimize a convex surrogate of the 0–1 loss function. The convexity makes these algorithms computationally efficient. The use of a surrogate, however, has statistical consequences that must be balanced against the computational virtues of convexity. To study these issues, we provide a general quantitative relationship between the risk as assessed using the 0–1 loss and the risk as assessed using any nonnegative surrogate loss function. We show that this relationship gives nontrivial upper bounds on excess risk under the weakest possible condition on the loss function—that it satisfies a pointwise form of Fisher consistency for classification. The relationship is based on a simple variational transformation of the loss function that is easy to compute in many applications. We also present a refined version of this result in the case of low noise, and show that in this case, strictly convex loss functions lead to faster rates of convergence of the risk than would be implied by standard uniform convergence arguments. Finally, we present applications of our results to the estimation of convergence rates in function classes that are scaled convex hulls of a finite-dimensional base class, with a variety of commonly used loss functions.
TLR8-dependent TNF-α overexpression in Fanconi anemia group C cells (2009)

Tumor necrosis factor alpha (TNF-alpha) production is abnormally high in Fanconi anemia (FA) cells and contributes to the hematopoietic defects seen in FA complementation group C-deficient (Fancc(-/-)) mice. Applying gene expression microarray and proteomic methods to studies on FANCC-deficient cells we found that genes encoding proteins directly involved in ubiquitinylation are overrepresented in the signature of FA bone marrow cells and that ubiquitinylation profiles of FA-C and complemented cells were substantially different. Finding that Toll-like receptor 8 (TLR8) was one of the proteins ubiquitinylated only in mutant cells, we confirmed that TLR8 (or a TLR8-associated protein) is ubiquitinylated in mutant FA-C cells and that TNF-alpha production in mutant cells depended upon TLR8 and the canonical downstream signaling intermediates interleukin 1 receptor-associated kinase (IRAK) and IkappaB kinase-alpha/beta. FANCC-deficient THP-1 cells and macrophages from Fancc(-/-) mice overexpressed TNF-alpha in response to TLR8 agonists but not other TLR agonists. Ectopically expressed FANCC point mutants were capable of fully complementing the mitomycin-C hypersensitivity phenotype of FA-C cells but did not suppress TNF-alpha overproduction. In conclusion, FANCC suppresses TNF-alpha production in mononuclear phagocytes by suppressing TLR8 activity and this particular function of FANCC is independent of its function in protecting the genome from cross-linking agents.
[Old spinal cord injury treated by pulsed electric stimulation]. (1992)

From March 1989 to May 1990, 80 cases of old spinal cord injury were treated with pulsed electric stimulation. The pulsed electric field was formed by utilizing paradural needle electrodes positioned cephalad and caudad to the site of spinal cord injury, with the stimulator connected with the electrodes being turned on. This stimulation was given 30 minutes once daily. 13 cases were treated for 3-6 months, 57 for 6-12 months, and 10 for 12-18 months. The nerve functions recovered in 78.5% of the cases (63/80), with the rate of useful recovery of 47.5% (38/80). The rate of EMG and gait improvement were 75.5% and 77.7%, respectively. The effect of pulsed electric stimulations was related to the extent of spinal cord injury, the depth and position of needle electrodes, the frequency and intensity of pulsed current and whether the spinal cord was compressed.
Cardiomyopathy in ostriches (Struthio camelus) due to avocado (Persea americana var. guatemalensis) intoxication. (1994)

Nine out of 120 ostriches died from congestive heart failure within 96 h of ingesting avocado leaves and immature fruit in an avocado orchard containing Hass and Fuerte cultivars. Foliage and immature fruit from both cultivars dosed to ostriches (n = 4) and domestic hens (n = 8) resulted in severe cardiomyopathy in all the ostriches. In the hens, which had received a lower dose, milder lesions occurred. Macroscopically the intoxication in ostriches resulted in a severe anasarca of the neck and ventral body. The cardiomyopathy was characterised by degeneration and necrosis of myocytes, a marked infiltration of heterophils and in one case, early fibroplasia.
Animal Models of Atherosclerosis and Interpretation of Drug Intervention Studies (1970)

Atherosclerosis has often been defined as a multifactoral disease; however, a common risk factor associated with accelerated vascular disease in man or animals is an elevated plasma cholesterol level. Even though there is no one perfect animal model that completely replicates the stages of human atherosclerosis, cholesterol feeding and mechanical endothelial injury are two common features shared by most models of atherosclerosis. The models may differ with respect to degree of dietary cholesterol supplementation, length of hypercholesterolemia, dietary regimen and type, duration and degree of mechanical endothelial injury. With the advent of genetic engineering, transgenic mouse models have supplemented the classical dietary cholesterol induced disease models such as the cholesterol-fed hamster, rabbit, pig and monkey. The desire to limit the progression of atherosclerosis has spawned numerous drug intervention studies. Biochemical as well as morphologic and morphometric changes in the extent, structure and composition of atherosclerotic lesions following drug intervention have become major endpoints of in vivo drug intervention studies. Interpretations of alterations in vascular pathology following drug administration are often confounded by associated changes in plasma lipids and lipoproteins, limitation of the animal models and additional properties of compounds unrelated to their primary mode of action. Thus, the current review will summarize the pathology of atherosclerosis, describe various animal models of vascular disease and provide a critical review of the methods utilized and conclusions drawn when evaluating pharmacologic agents in animals.
Chronic nicotine administration exacerbates tau pathology in a transgenic model of Alzheimer's disease (2005)

The association between nicotinic acetylcholine receptor (nAChR) dysfunction and cognitive decline in Alzheimer's disease (AD) has been widely exploited for its therapeutic potential. The effects of chronic nicotine exposure on Abeta accumulation have been studied in both humans and animal models, but its therapeutic efficacy for AD neuropathology is still unresolved. To date, no in vivo studies have addressed the consequences of activating nAChRs on tau pathology. To determine the effects of chronic nicotine administration on Abeta and tau pathology, we chronically administrated nicotine to a transgenic model of AD (3xTg-AD) in their drinking water. Here, we show that chronic nicotine intake causes an up-regulation of nicotinic receptors, which correlated with a marked increase in the aggregation and phosphorylation state of tau. These data show that nicotine exacerbates tau pathology in vivo. The increase in tau phosphorylation appears to be due to the activation of p38-mitogen-activated protein kinase, which is known to phosphorylate tau in vivo and in vitro. We also show that the 3xTg-AD mice have an age-dependent reduction of alpha7nAChRs compared with age-matched nontransgenic mice in specific brain regions. The reduction of alpha7nAChRs is first apparent at 6 months of age and is restricted to brain regions that show intraneuronal Abeta(42) accumulation. Finally, this study highlights the importance of testing compounds designed to ameliorate AD pathology in a model with both neuropathological lesions because of the differential effects it can have on either Abeta or tau.
Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors (1998)

Objective: It is our experience that many patients treated with proton pump inhibitors (PPI)b.i.d. recover acid secretion during the night. Our aim was to assess the efficacy of omeprazole and lansoprazoleb.i.d. on nocturnal gastric acidity. Methods: Three groups were studied with intragastric pH monitoring. Group 1 consisted of 17 patients with gastroesophageal reflux disease (GERD) taking omeprazole 20 mgb.i.d. Group 2 was 16 male volunteers taking omeprazole 20 mgb.i.d. and Group 3 comprised 12 volunteers taking lansoprazole 30 mgb.i.d.. Results: The percentages of time that subjects had pH < 4 were lower during supine than upright periods in Groups 1 and 3 (P< 0.01). Recovery of nocturnal acid secretion lasting > 1 h, termed acid breakthrough, occurred in three-fourths of all individuals within 12 h from intake of the evening dose of PPI. Median time to acid breakthrough for the whole group was 7.5 h. Conclusions: Nocturnal acid breakthrough occurs in a majority of patients and normal volunteers taking PPIb.i.d.
Purification of a Peptidoglycan Recognition Protein from Hemolymph of the Silkworm, Bombyx mori (1996)

A method was developed for obtaining a homogeneous silkworm hemolymph protein (peptidoglycan recognition protein, PGRP) which has affinity for peptidoglycan and the ability to trigger the prophenoloxidase cascade upon its binding to peptidoglycan. The purified PGRP had a molecular mass of about 19 kDa and is composed of a single polypeptide with an isoelectric point of 6.5. It bound to peptidoglycan in the absence of divalent cation, whereas its binding to beta1,3-glucan and chitin was not detected. N-Acetyl-D-glucosaminyl-(beta1-4)-N-acetylmuramyl-L-alanyl-D-isogluta mine did not inhibit purified PGRP to bind insoluble peptidoglycan, but fragmented soluble peptidoglycan did. PGRP seemed to require peptidoglycan as a possible ligand to keep its glycan portion consisting of at least two or more of the repeating unit. PGRP did not have any detectable lysozyme activity, and its amino acid composition and amino-terminal sequence of 20 amino acid residues were shown to be different from those of silkworm lysozyme. PGRP seems to be a hitherto unknown protein. In the absence of PGRP, the prophenoloxidase cascade in the plasma fraction of hemolymph could not be triggered by peptidoglycan, indicating that some type of activity, capable of activating the cascade, is generated upon their binding. However, the exact nature of this activity is not yet known. The purified PGRP bound to peptidoglycan did not hydrolyze significantly any of the 26 commercially available peptidyl-7-amino-4-methylcoumarins, substrates for various proteases.
Fluoroalkyl Silane Modified Silicone Rubber/Nanoparticle Composite: A Super Durable, Robust Superhydrophobic Fabric Coating (2012)

A superhydrophobic fabric coating made of a crosslinked polydimethylsiloxane elastomer, containing well-dispersed hydrophobic silica nanoparticles and fluorinated alkyl silane, shows remarkable durability against repeated machine washes, severe abrasion, strong acid or base, boiling water or beverages and excellent stain resistance.
Characterization of human pregnancy zone protein. Comparison with human alpha 2-macroglobulin. (1985)

Native human pregnancy zone protein (PZP), a close homolog of alpha 2-macroglobulin (alpha 2M), can be obtained in approximately 20% yield from pooled late pregnancy plasma or serum by a combination of polyethylene glycol precipitation, euglobulin precipitation, DEAE-Sephacel chromatography, zinc-chelate affinity chromatography, and negative affinity chromatography on insolubilized antibodies against human serum proteins. Both proteins are similarly organized as disulfide-bridged dimers of 360 kDa containing 180-kDa subunits. These dimers constitute the proteinase-binding units of PZP, and in contrast to alpha 2M, they appear to be only loosely associated, indicating a subtle difference in the quaternary structure of these alpha-macroglobulins. The preparations contain functionally intact beta-cysteinyl-gamma-glutamyl thiol esters, located in the same nonapeptide sequence as found in alpha 2M, and form complexes with a variety of proteinases in which a large fraction of the proteinase is bound covalently. Proteinases bound to PZP are still active and poorly accessible to reaction with large inhibitors like alpha 1-proteinase inhibitor. The structural and functional features of PZP indicate that PZP and alpha 2M, although extremely similar, may have different yet overlapping sets of proteinases as targets. It is possible that PZP mainly controls the activity of cellular proteinases released under conditions of increased cellular turnover and that PZP could be the human equivalent to the acute phase alpha-macroglobulins known in other species.
Predicting Nanocrystal Shape through Consideration of Surface-Ligand Interactions (2012)

Density functional calculations for the binding energy of oleic acid-based ligands on Pb-rich {100} and {111} facets of PbSe nanocrystals determine the surface energies as a function of ligand coverage. Oleic acid is expected to bind to the nanocrystal surface in the form of lead oleate. The Wulff construction predicts the thermodynamic equilibrium shape of the PbSe nanocrystals. The equilibrium shape is a function of the ligand surface coverage, which can be controlled by changing the concentration of oleic acid during synthesis. The different binding energy of the ligand on the {100} and {111} facets results in different equilibrium ligand coverages on the facets, and a transition in the equilibrium shape from octahedral to cubic is predicted when increasing the ligand concentration during synthesis.
Preface to the second edition (2001)

Since the appearance of the first edition of this book, the range of Spanish-language reference material has been transformed by a significant number of welcome additions and developments. Larger and more comprehensive Spanish/English bilingual dictionaries, based on huge electronic corpora and incorporating much information on register usage, have been published by Collins, Oxford University Press and Larousse; the CLAVE Diccionario del uso del español (Madrid: Ediciones SM) has brought the illustration of word meaning through contextual example to a fine art; substantial on-line corpora have been made available by the Real Academia Española (www.rae.es) and by Professor Mark Davies (www.corpusdelespanol.org), and the presence of Spanish on the Internet provides a wealth of linguistic information. We enthusiastically commend such rich resources. However, the purpose of this book remains what it was, that of providing a selective guide to areas of Spanish usage which we know through years of teaching experience pose problems for English-speaking learners, and we hope that, as such, it will be clear, easy to use and not too daunting. We have therefore retained the style and the bulk of the material of the original project whilst taking the opportunity to make some changes, additions and updatings. Some of the chapters on vocabulary have been completely rewritten and extended, and there are new chapters on anglicisms and on semi-technical vocabulary. We have continued to focus on vocabulary and grammar, and there is no systematic treatment of pronunciation or of essentially morphological features such as verb forms.
Resonant Polymeric Waveguide Cantilever Integrated for Optical Scanning (2007)

We present SU-8 as an optical waveguide and its integration into a functional one- and two-dimensional (1-D and 2-D) scanning device. The waveguide is fabricated as a tapered structure and cantilever beam (100times85times2100 mum). It is mounted onto a 2-D coupled bimorph piezoelectric actuator and driven at resonant frequencies of 4.71 kHz in the vertical and 25 Hz in the horizontal. This raster motion allows for 2-D image scanning when in combination with a light source and detector. An analysis of the polymer's optical capabilities has shown mode coupling efficiencies of 96% and measured a total power output intensity of 20% with a 633-nm light source. The output power can be attributed to the butt-end coupling misalignment, scattering losses due to surface roughness, and absorption. The total vertical tip displacement is 669 mum with an angle of 25 deg when driven with a 47-mum base excitation. A specific application for the design is in the area of endoscopy, where there is a need for a minimally invasive device that reduces the discomfort experienced by the patient. SU-8 as the functional waveguide is the initial phase in creating a microfabricated endoscope system
Transformation of Maize Using Silicon Carbide Whiskers (2003)

As the most commercially valuable cereal grown worldwide and the best-characterized in genetic terms, maize was predictably the first target for transformation among the important crops. Indeed, the first attempt at transformation of any plant was conducted on maize (1). These early efforts, however, were inevitably unsuccessful, since at that time, there were no reliable methods to permit the introduction of DNA into a cell, the expression of that DNA, and the identification of progeny derived from such a “transgenic” cell (2). Almost 20 years later, these technologies were finally combined, and the first transgenic cereals were produced. In the last few years, methods have become increasingly efficient, and transgenic maize has now been produced from protoplasts as well as from Agrobacterium-medieited or “Biolistic” delivery to embryogenic tissue (for a general comparison of methods used for maize, the reader is referred to a recent review—ref. 3). The present chapter will describe probably the simplest of the available procedures, namely the delivery of DNA to the recipient cells by vortexing them in the presence of silicon carbide (SiC) whiskers (this name will be used in preference to the term “fiber,” since it more correctly describes the single crystal nature of the material).
Altered metabolism of poly(adp‐ribose) in the peripheral blood lymphocytes of patients with systemic lupus erythematosus (1989)

A method was developed to measure poly(ADP-ribose) metabolism in peripheral blood lymphocytes. The technique involved the isolation of lymphocytes on Ficoll gradients, followed by lysis with 5M NaCl. The synthesis and degradation of poly(ADP-ribose) in this crude lysate, measured by the incorporation of 3H-labeled NAD into acid-precipitable counts, was compared in 18 patients with systemic lupus erythematosus (SLE), 10 patients with rheumatoid arthritis, and in 10 control patients without rheumatoid arthritis. Patients with SLE showed a 70% decrease in poly(ADP-ribose) synthesis (P less than 0.001); this decreased synthesis persisted even with the addition of histones or DNase. We present possible explanations of the role of poly(ADP-ribose) in SLE.
Monocyte chemotactic protein-1 (MCP-1), -2, and -3 are chemotactic for human T lymphocytes. (1995)

Monocyte chemotactic protein (MCP)-1, -2, and -3 all have been shown to induce monocyte/macrophage migration in vitro and MCP-1, also known as MCAF, chemoattracts basophils and mast cells. We report here that natural MCP-1 as well as synthetic preparations of MCP-2 and MCP-3 stimulate significant in vitro chemotaxis of human peripheral blood T lymphocytes. This MCP-induced migration was dose-dependent and directional, but not chemokinetic. Phenotypic analysis of the T cell population responsive to MCP-1, MCP-2, and MCP-3 demonstrates that both CD4+ and CD8+ T cells migrated in response to these chemokines. Similar results were observed using human CD4+ and CD8+ T cell clones. Neutralizing antisera to MCAF or MCP-2 abrogated T cell migration in response to MCP-1 and MCP-2, respectively, but not to RANTES. Subcutaneous administration of purified MCP-1 into the hind flanks of SCID mice engrafted with human peripheral blood lymphocytes (PBL) induced significant human CD3+ T cell infiltration into the site of injection at 4 h. These results demonstrate that MCP-1, MCP-2, and MCP-3 are inflammatory mediators that specifically stimulate the directional migration of T cells as well as monocytes and may play an important role in immune cell recruitment into sites of antigenic challenge.
Stromelysin and tissue inhibitor of metalloproteinases gene expression in rheumatoid arthritis synovium. (1992)

In situ hybridization was used to localize stromelysin mRNA in rheumatoid arthritis synovial tissue. Stromelysin antisense probes hybridized primarily to the intimal lining layer in frozen tissue sections, with little or no sublining signal. The expression of stromelysin correlated with cellularity as determined by hybridization with an actin probe. Double-label experiments were performed to detect tissue inhibitor of metalloproteinases (TIMP) and stromelysin mRNA simultaneously in synovial tissue. Coexpression of both mRNA species was identified in a subpopulation of intimal lining cells. In some highly inflammatory tissues, virtually all of the lining cells hybridized to both probes. However, in other tissues, expression of the two genes was discordant, with large numbers of TIMPpositive/stromelysin(negative) cells. Similar results were observed with late-passage cultured synoviocytes. Unstimulated cells did not express the stromelysin gene, whereas TIMP was constitutively produced. Addition of interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) to cultures induced the former but had little effect on the latter. Double-label experiments clearly showed discordant expression in individual cells. Stromelysin and TIMP genes likely have distinct transcriptional controls that provide precise control over the local environment and matrix turnover.