gebhart/patrepeval huggingface dataset:
Detection of anti-PL-12 autoantibodies by ELISA using a recombinant antigen; study of the immunoreactive region (1998)

Autoantibodies to aminoacyl-tRNA synthetases are highly associated with myositis and detection is important in clinical diagnosis; however, current methods of screening limit its clinical utility. In the present study, alanyl-tRNA synthetase (PL-12) recombinant protein was obtained by immunological screening of a HeLa expression library and used in an ELISA with 22 anti-PL-12 sera, 200 autoimmune sera negative for PL-12 and 100 healthy individual sera. Sensitivity of the method was 95% (21/22) and specificity 100%. Mapping of the immunoreactive region was carried out using three anti-PL-12 sera and different recombinant protein-derived peptides. Results show that the same conformational epitope located within amino acids 730-951 of the PL-12 antigen outside the catalytic region was recognized by the three anti-PL-12 sera tested. We conclude that ELISA using recombinant protein is an effective and useful method for routine screening for anti-PL-12 autoantibodies.
Activation-dependent Adhesion of Human Platelets to Cyr61 and Fisp12/Mouse Connective Tissue Growth Factor Is Mediated through Integrin αIIbβ3 (1999)

Cyr61 and connective tissue growth factor (CTGF), members of a newly identified family of extracellular matrix-associated signaling molecules, are found to mediate cell adhesion, promote cell migration and enhance growth factor-induced cell proliferation in vitro, and induce angiogenesis in vivo. We previously showed that vascular endothelial cell adhesion and migration to Cyr61 and Fisp12 (mouse CTGF) are mediated through integrin alpha(v)beta(3). Both Cyr61 and Fisp12/mCTGF are present in normal blood vessel walls, and it has been demonstrated that CTGF is overexpressed in advanced atherosclerotic lesions. In the present study, we examined whether Cyr61 and Fisp12/mCTGF could serve as substrates for platelet adhesion. Agonist (ADP, thrombin, or U46619)-stimulated but not resting platelets adhered to both Cyr61 and Fisp12/mCTGF, and this process was completely inhibited by prostaglandin I(2), which prevents platelet activation. The specificity of Cyr61- and Fisp12/mCTGF-mediated platelet adhesion was demonstrated by specific inhibition of this process with polyclonal anti-Cyr61 and anti-Fisp12/mCTGF antibodies, respectively. The adhesion of ADP-activated platelets to both proteins was divalent cation-dependent and was blocked by RGDS, HHLGGAKQAGDV, or echistatin, but not by RGES. Furthermore, this process was specifically inhibited by the monoclonal antibody AP-2 (anti-alpha(IIb)beta(3)), but not by LM609 (anti-alpha(v)beta(3)), indicating that the interaction is mediated through integrin alpha(IIb)beta(3). In a solid phase binding assay, activated alpha(IIb)beta(3), purified by RGD affinity chromatography, bound to immobilized Cyr61 and Fisp12/mCTGF in a dose-dependent and RGD-inhibitable manner. In contrast, unactivated alpha(IIb)beta(3) failed to bind to either protein. Collectively, these findings identify Cyr61 and Fisp12/mCTGF as two novel activation-dependent adhesive ligands for the integrin alpha(IIb)beta(3) on human platelets, and implicate a functional role for these proteins in hemostasis and thrombosis.
Occluded and nonoccluded nuclear polyhedrosis virus grown in Trichoplusia ni: comparative neutralization comparative infectivity, and in vitro growth studies (1976)

Nuclear polyhedrosis virus infections of lepidopteran cells often result in the production of both occluded and nonoccluded virus. The characterization of these two different forms has been the subject of several papers. We have divided the nonoccluded virus (NOV) category further into plasma membrane-budded non-occluded virus (PMB-NOV), intracellular NOV, and hemolymph-derived NOV, and have done additional studies investigating the differences between these nonoccluded forms and the alkali-liberated forms from occlusions of the nuclear polyhedrosis viruses of Autographa californica and Rachiplusa ou. The methods used to discern differences and similarities among the forms were serological, biochemical, and visual, all related to their biological acitivity. Neutralization studies revealed that alkali-liberated virus and PMB-NOV had both similar and different antigens. Antisera raised against alkali-liberated virus from occlusions neutralized the alkali-liberated form of the virus, but did not neutralize the intracellular or extracellular nonoccluded forms. Antisera raised against the TN-368-13 PMB-NOV, however, neutralized the alkali-liberated forms as well as all forms of the NOV. Adsorption of this antisera with alkali-liberated virus did not diminish the neutralization titer against the nonoccluded forms, thus confirming the antigenic differences between the alkali-liberated and nonoccluded forms of the virus. Physical-infectious particle ratio calculations indicated that the PMB-NOV of Autographa californica are about 1,900-fold more infectious than the single-nucleocapsid-per-envelope alkali-liberated particles and about 1,700-fold more infectious than the multiple-nucleocapsid-per-envelope particles, as assayed in vitro. In addition, a study of viral growth kinetics monitored concurrently with the appearance of polyhedra showed that PMB-NOV production is shut down with the onset of polyhedron formation.
Wiring Telephone Apparatus from Computer-Generated Speech (1972)

Tape-recorded, spoken wiring instructions eliminate the need for a wireman to divert his eyes and hands from the equipment he is fabricating. A computer technique is described for automatically converting printed wire lists to synthetic speech. The technique was used to synthesize spoken wire lists for crossbar-4 equipment, and the result was tested informally on a production line at the Western Electric Company plant in Oklahoma City. No errors were made in wiring crossbar-4 circuitry from the computer-synthesized instructions.
Transcytosis of cholera toxin subunits across model human intestinal epithelia. (1995)

Cholera toxin (CT) elicits a massive secretory response from intestinal epithelia by binding apical receptors (ganglioside GM1) and ultimately activating basolateral effectors (adenylate cyclase). The mechanism of signal transduction from apical to basolateral membrane, however, remains undefined. We have previously shown that CT action on the polarized human intestinal epithelial cell line T84 requires endocytosis and processing in multiple intracellular compartments. Our aim in the present study was to test the hypothesis that CT may actually move to its site of action on the basolateral membrane by vesicular traffic. After binding apical receptors, CT entered basolaterally directed transcytotic vesicles. Both CT B subunits and to a lesser extent CT A subunits were delivered intact to the serosal surface of the basolateral membrane. The toxin did not traverse the monolayer by diffusion through intercellular junctions. Transcytosis of CT B subunits displayed nearly identical time course and temperature dependency with that of CT-induced Cl- secretion--suggesting the two may be related. These data identify a mechanism that may explain the link between the toxin's apical receptor and basolateral effector.
Protection of HIF-1-deficient primary renal tubular epithelial cells from hypoxia-induced cell death is glucose dependent (2005)

Ischemic acute renal failure is a frequent clinical problem in hospitalized patients and is associated with significant mortality. Hypoxia-inducible factor 1 (HIF-1) mediates cellular adaptation to hypoxia by regulating biological processes important for cell survival, which include glycolysis, angiogenesis, erythropoiesis, apoptosis, and proliferation. To investigate the role of HIF-1 in hypoxia-induced renal epithelial cell death, we generated mice that allow inactivation of HIF-1alpha by tetracycline-inducible Cre-loxP-mediated recombination in primary renal proximal tubule cells (PRPTC), resulting in a suppression of HIF-1-mediated gene transcription during oxygen deprivation. In the absence of glucose, the onset and the degree of hypoxia-induced cell death in HIF-1-deficient PRPTC were comparable to wild-type cells. However, when glucose availability was limited, the onset of cell death was delayed in either PRPTC that were HIF-1 deficient or in wild-type PRPTC when glycolysis or glucose uptake was partially inhibited. Our findings suggest in an in vitro genetic model that 1) the generation of adequate energy levels for the maintenance of PRPTC viability under hypoxia does not require HIF-1 and 2) that HIF-1 regulates the timing of hypoxia-induced cell death and apoptosis onset through its effects on glucose consumption.
Learning Globally-Consistent Local Distance Functions for Shape-Based Image Retrieval and Classification (2007)

We address the problem of visual category recognition by learning an image-to-image distance function that attempts to satisfy the following property: the distance between images from the same category should be less than the distance between images from different categories. We use patch-based feature vectors common in object recognition work as a basis for our image-to-image distance functions. Our large-margin formulation for learning the distance functions is similar to formulations used in the machine learning literature on distance metric learning, however we differ in that we learn local distance functions-a different parameterized function for every image of our training set-whereas typically a single global distance function is learned. This was a novel approach first introduced in Frome, Singer, & Malik, NIPS 2006. In that work we learned the local distance functions independently, and the outputs of these functions could not be compared at test time without the use of additional heuristics or training. Here we introduce a different approach that has the advantage that it learns distance functions that are globally consistent in that they can be directly compared for purposes of retrieval and classification. The output of the learning algorithm are weights assigned to the image features, which is intuitively appealing in the computer vision setting: some features are more salient than others, and which are more salient depends on the category, or image, being considered. We train and test using the Caltech 101 object recognition benchmark.
Inhibition of Luminescence and Virulence in the Black Tiger Prawn ( Penaeus monodon ) Pathogen Vibrio harveyi by Intercellular Signal Antagonists (2000)

Expression of luminescence in the Penaeus monodon pathogen Vibrio harveyi is regulated by an intercellular quorum sensing mechanism involving the synthesis and detection of two signaling molecules, one of which is N-hydroxy butanoyl-L-homoserine lactone and the other of which is uncharacterized. Indirect evidence has suggested that virulence, associated with a toxic extracellular protein, and luminescence in V. harveyi are coregulated. In this study the effects of an acylated homoserine lactone antagonist produced by the marine alga Delisea pulchra on luminescence and toxin production in a virulent strain of V. harveyi were analyzed. Luminescence and toxin production were both inhibited by the signal antagonist at concentrations that had no impact on growth. Toxin production was found to be prematurely induced in V. harveyi cultures incubated in a 10% conditioned medium. Additionally, a significant reduction in the toxicity of concentrated supernatant extracts from V. harveyi cultures incubated in the presence of the signal antagonist, as measured by in vivo toxicity assays in mice and prawns, was observed. These results suggest that intercellular signaling antagonists have potential utility in the control of V. harveyi prawn infections.
Synthesis, Characterization, and Gas Permeation Properties of a Novel Group of Polymers with Intrinsic Microporosity: PIM-Polyimides (2009)

A range of polyimides with characteristics similar to a polymer of intrinsic microporosity (PIM) were prepared by reaction with various aromatic diamines of a bis(carboxylic anhydride) incorporating a spiro-center. The polymers exhibited high surface area, as determined by nitrogen adsorption, and high thermal stability. Membrane gas permeation experiments showed PIM-polyimides to be among the most permeable of all polyimides and to have selectivities close to the upper bound for several important gas pairs. A group contribution method was used to predict permeability coefficients and separation factors for further PIM-polyimide structures, revealing worthwhile targets for future synthetic efforts.
Synthesis of Novel β-Lactone Inhibitors of Fatty Acid Synthase (2008)

Fatty acid synthase (FAS) is necessary for growth and survival of tumor cells and is a promising drug target for oncology. Here, we report on the syntheses and activity of novel inhibitors of the thioesterase domain of FAS. Using the structure of orlistat as a starting point, which contains a beta-lactone as the central pharmacophore, 28 novel congeners were synthesized and examined. Structural features such as the length of the alpha- and beta-alkyl chains, their chemical composition, and amino ester substitutions were altered and the resulting compounds explored for inhibitory activity toward the thioesterase domain of FAS. Nineteen congeners show improved potency for FAS in biochemical assays relative to orlistat. Three of that subset, including the natural product valilactone, also display an increased potency in inducing tumor cell death and improved solubility compared to orlistat. These findings support the idea that an orlistat congener can be optimized for use in a preclinical drug design and for clinical drug development.
A microprocessor based photoplethysmograph for use in clinical practice (1995)

A microprocessor-based system of photoplethysmography and its use in measuring skin blood flow is described. The system was designed specifically for use over long periods and for the analysis of the output to be handled by a personal computer. The photoplethysmograph described in this paper is shown to be a qualitative method for assessment of changes in peripheral skin blood flow. There is potential for use of this instrument in a variety of clinical conditions.
Laser Fabrication of Three-Dimensional CAD Scaffolds from Photosensitive Gelatin for Applications in Tissue Engineering (2011)

In the present work, 3D CAD scaffolds for tissue engineering applications were developed starting from methacrylamide-modified gelatin (GelMOD) using two-photon polymerization (2PP). The scaffolds were cross-linked employing the biocompatible photoinitiator Irgacure 2959. Because gelatin is derived from collagen (i.e., the main constituent of the ECM), the developed materials mimic the cellular microenvironment from a chemical point of view. In addition, by applying the 2PP technique, structural properties of the cellular microenvironment can also be mimicked. Furthermore, in vitro degradation assays indicated that the enzymatic degradation capability of gelatin is preserved for the methacrylamide-modified derivative. An in depth morphological analysis of the 2PP-fabricated scaffolds demonstrated that the parameters of the CAD model are reproduced with great precision, including the ridge-like surface topography on the order of 1.5 μm. The developed scaffolds showed an excellent stability in culture medium. In a final part of the present work, the suitability of the developed scaffolds for tissue engineering applications was verified. The results indicated that the applied materials are suitable to support porcine mesenchymal stem cell adhesion and subsequent proliferation. Upon applying osteogenic stimulation, the seeded cells differentiated into the anticipated lineage. Energy dispersive X-ray (EDX) analysis showed the induced calcification of the scaffolds. The results clearly indicate that 2PP is capable of manufacturing precisely constructed 3D tissue engineering scaffolds using photosensitive polymers as starting material.
The therapeutic activity of 1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid monohydrate glucosamide in rheumatoid arthritis (double blind trial). (1975)

A new nonsteroidal anti-inflammatory agent, 1-(p-chlorobenzyl)-5-methylindole-3-acetic acid monohydrate glucosamide (glucametacine, Teoremac¿), was used in the treatment of a total of 39 patients including 31 cases of rheumatoid arthritis, 3 of ankylosing spondylitis, 1 of psoriatic rheumatism, 1 of chronic chondrocalcinosis and 3 of arthrosis. Teoremac was given for 14 days at a dosage of 420 mg/day. The drug was shown to be more or less active in all the patients except 4. The improvement in the various clinical parameters of rheumatoid arthritis studied was statistically significant. The side effects recorded were headache, which was severe in only 1 case, and "minor" disturbances of the gastro-intestinal tract. A double blind crossover trial was carried out in 15 patients with rheumatoid arthritis to compare the action of Teoremac (420 mg/day for 14 days) with that of indometacin (100 mg/day for 14 days). Under the conditions of the trial, the clinical findings showed Teoremac to be slightly superior to indometacin, but the difference was not significant statistically.
Targeted Gene Delivery: Importance of Administration Routes (2013)

Gene therapy is a promising approach to treat intractable and refractory diseases at the genetic level. Basically, in gene therapy, target gene expression is induced by delivering foreign genes. Downregulation of target gene expression or gene silencing can also be performed using miRNA, siRNA or shRNA expression vectors [1]. Gene therapy is useful for both genetic and acquired diseases. For genetic diseases, the first clinical trial was performed for adenosine deaminase deficiency in 1990 [2]. Subsequently, numerous clinical trials were carried out for other congenital genetic defects such as familial hypercholesterolemia and cystic fibrosis [3]. Gene therapy clinical trials were also performed for acquired diseases such as cancers, cardiovascular diseases and infectious diseases [3].
Folding-based electrochemical DNA sensor fabricated by “click” chemistry (2009)

Here we report a folding-based electrochemical DNA (E-DNA) sensor fabricated by Sharpless "click" chemistry; the "click" chemistry-based E-DNA sensor compares favorably to a sensor fabricated via the conventional "two-step approach".
Personal Dynamic Media (1977)

The Learning Research Group at Xerox Palo Alto Research Center is concerned with all aspects of the communication and manipulation of knowledge. We design, build, and use dynamic media which can be used by human beings of all ages. Several years ago, we crystallized our dreams into a design idea for a personal dynamic medium the size of a notebook (the Dynabook) which could be owned by everyone and could have the power to handle virtually all of its owner's information-related needs. Towards this goal we have designed and built a communications system: the Smalltalk language, implemented on small computers we refer to as "interim Dynabooks." We are exploring the use of this system as a programming and problem solving tool; as an interactive memory for the storage and manipulation of data; as a text editor; and as a medium for expression through drawing, painting, animating pictures, and composing and generating music. (Figure 1 is a view of this interim Dynabook.)
In vitro negative selection of αβ T cell receptor transgenic thymocytes by conditionally immortalized thymic cortical epithelial cell lines and dendritic cells (1993)

We have established conditionally immortalized thymic cortical epithelial cell lines from transgenic mice carrying a temperature-sensitive SV40 large T antigen. One of these cell lines expresses cortical markers and produces IL-1 alpha, IL-6, IL-7, and TGF-beta 1. These cells express class I major histocompatibility complex (MHC) constitutively and class II MHC upon induction with IFN-gamma. The cells appear to have a normal class I antigen presenting pathway since messages for both peptide transporter genes (TAP1, TAP2) were detected. The ability of these cortical epithelial cells to present peptide antigen was compared to that of thymic dendritic cells. In suspension culture with alpha beta T cell receptor (TcR) transgenic thymocytes, these epithelial cells and dendritic cells (pre-pulsed with peptide cognate for the transgenic TcR) caused down-regulation of CD4, CD8, and TcR in an antigen dose-dependent and MHC-restricted manner. CD4dullCD8dull cells were taken as evidence for negative selection because these cells contained apoptotic DNA. Concentration of peptide required for negative selection of thymocytes was similar between dendritic cells and cortical epithelial cells. In contrast, alpha beta TcR transgenic spleen cells were activated only by dendritic cells but not by cortical epithelial cells.
Vitamin E in Humans: Demand and Delivery (1996)

How much vitamin E is enough? An established use of supplemental vitamin E in humans is in the prevention and therapy of deficiency symptoms. The cause of vitamin E deficiency, characterized by peripheral neuropathy and ataxia, is usually malabsorption-a result of fat malabsorption or genetic abnormalities in lipoprotein metabolism. Genetic abnormalities in the hepatic alpha-tocopherol transfer protein also cause vitamin E deficiency-defects in this protein cause an impairment in plasma vitamin E transport. Impaired delivery of vitamin E to tissues, thereby, results in deficiency symptoms. Also discussed is the use of supplemental vitamin E in chronic diseases such as ischemic heart disease, atherosclerosis, diabetes, cataracts, Parkinson's disease, Alzheimer's disease, and impared immune function, as well as in subjects receiving total parenterol nutrition. In healthy individuals, a daily intake of about 15-30 mg of alpha-tocopherol is recommended to obtain "optimal plasma alpha-tocopherol concentrations" (30 microM or greater).
sar: a genetic mouse model for human sarcosinemia generated by ethylnitrosourea mutagenesis. (1992)

A mouse mutant with sarcosinemia was found by screening the progeny of ethylnitrosourea-mutagenized mice for aminoacidurias. Paper chromatography, column chromatography, and gas chromatography-mass spectrometry identified high levels of sarcosine in the urine of the mutant mice. While sarcosine cannot be detected in the urine of plasma of normal mice, the urinary sarcosine level of 102 +/- 58 mmol per g of creatinine in the mutant mice was at the upper range of the urinary levels (1.5-4.5 mmol of sarcosine per g of creatinine) observed in humans with sarcosinemia. Similarly, the plasma sarcosine level of 785 +/- 153 mumol/liter in the sarcosinemic mice was at the upper range of the plasma sarcosine levels (53-760 mumol/liter) observed in affected humans. Sarcosine dehydrogenase [sarcosine:(acceptor) oxidoreductase (demethylating), EC 1.5.99.1] activity was deficient in sarcosinemic mice. The sarcosinuria phenotype in these mice was inherited as an autosomal recessive trait. This mouse mutant provides a useful genetic model for human sarcosinemia and for development of therapeutic approaches for genetic disease.