gebhart/patrepeval huggingface dataset:
The collagen-platelet interaction (1998)

Collagen-platelet interaction, occurring in hemostasis but also a cause of thrombosis, is a two-step process of adhesion and activation involving the sequential recognition of distinct receptors. Adhesion involves first the reversible recognition of collagen-bound von Willebrand factor by the platelet receptor complex Gp Ib/IX/V, followed by direct interaction between collagen and the platelet integrin receptor alpha2beta1, which binds to specific sequences in collagen in which the GER motif appears important. Platelet activation then follows from the recognition by the receptor Gp VI of GPP* sequences in collagen, culminating in signalling events unique to collagen as a platelet agonist: Gp VI leads via the novel platelet Fc receptor gamma-chain to p72syk and phospholipase Cgamma2.
Robust linear dimensionality reduction (2004)

We present a novel family of data-driven linear transformations, aimed at finding low-dimensional embeddings of multivariate data, in a way that optimally preserves the structure of the data. The well-studied PCA and Fisher's LDA are shown to be special members in this family of transformations, and we demonstrate how to generalize these two methods such as to enhance their performance. Furthermore, our technique is the only one, to the best of our knowledge, that reflects in the resulting embedding both the data coordinates and pairwise relationships between the data elements. Even more so, when information on the clustering (labeling) decomposition of the data is known, this information can also be integrated in the linear transformation, resulting in embeddings that clearly show the separation between the clusters, as well as their internal structure. All of this makes our technique very flexible and powerful, and lets us cope with kinds of data that other techniques fail to describe properly.
Fish and Heart Disease (1995)

Epidemiologic and laboratory investigations suggest that eating fish confers protection against coronary heart disease.1,2 However, in this issue of the Jour-nal, Ascherio et al.3 report no association between fish intake and coronary heart disease in the Health Professionals Follow-up Study. Where does the evidence stand, and how do the new data fit in?Fish and other seafoods, and oils pressed from them, contain a special class of polyunsaturated fatty acids called omega-3 or n-3 (“n minus three”) fatty acids. Tiny amounts of these are essential for the development of the nervous system. The effect of n-3 fatty acids on . . .
Enhancing the Development and Approval of Acute Stroke Therapies (2005)

The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.
Prediction of a gene regulatory network linked to prostate cancer from gene expression, microRNA and clinical data (2010)

The complete regulatory network is available as an interactive supplementary web site at the following URL: http://bioinformatics.psb.ugent.be/webtools/pronet/.
BIOMIMETIC ACTINIDE CHELATORS: AN UPDATE ON THE PRECLINICAL DEVELOPMENT OF THE ORALLY ACTIVE HYDROXYPYRIDONATE DECORPORATION AGENTS 3,4,3-LI(1,2-HOPO) AND 5-LIO(ME-3,2-HOPO) (2010)

The threat of a dirty bomb or other major radiological contamination presents a danger of large-scale radiation exposure of the population. Because major components of such contamination are likely to be actinides, actinide decorporation treatments that will reduce radiation exposure must be a priority. Current therapies for the treatment of radionuclide contamination are limited and extensive efforts must be dedicated to the development of therapeutic, orally bioavailable, actinide chelators for emergency medical use. Using a biomimetic approach based on the similar biochemical properties of plutonium(IV) and iron(III), siderophore-inspired multidentate hydroxypyridonate ligands have been designed and are unrivaled in terms of actinide-affinity, selectivity, and efficiency. A perspective on the preclinical development of two hydroxypyridonate actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), is presented. The chemical syntheses of both candidate compounds have been optimized for scale-up. Baseline preparation and analytical methods suitable for manufacturing large amounts have been established. Both ligands show much higher actinide-removal efficacy than the currently approved agent, diethylenetriaminepentaacetic acid (DTPA), with different selectivity for the tested isotopes of plutonium, americium, uranium and neptunium. No toxicity is observed in cells derived from three different human tissue sources treated in vitro up to ligand concentrations of 1 mM, and both ligands were well tolerated in rats when orally administered daily at high doses (>100 micromol kg d) over 28 d under good laboratory practice guidelines. Both compounds are on an accelerated development pathway towards clinical use.
Design and analysis of switched-capacitor-based step-up resonant converters (2005)

A switched-capacitor-based step-up resonant converter is proposed. The voltage conversion of the converters is in step-up mode. By adding a different number of switched-capacitor cells, different output voltage conversion ratios can be obtained. The voltage conversion ratio from 2 to any whole number can therefore be generated by these switching-capacitor techniques. A resonant tank is used to assist in zero-current switching hence the current spike, which usually exists for classical switched-capacitor can be eliminated. Both high-frequency operations and high efficiency are possible. Generalized analysis and design method of the converters are also presented. Experimental results verified the theoretical analysis.
Diffusion tensor MRI of myocardial fibers and sheets: Correspondence with visible cut‐face texture (2002)

The results support a parallel relationship between the eigenvectors of the DT and symmetry axes of the myocardial architecture. Specifically, the first, second and third eigenvectors correspond to the fiber, sheet, and sheet normal directions, respectively.
Specificity of resistance to oxidative stress (2002)

Two clonal nerve-like cell lines derived from HT22 and PC12 have been selected for resistance to glutamate toxicity and amyloid toxicity, respectively. In the following experiments it was asked if these cell lines show cross-resistance toward amyloid beta peptide (Abeta) and glutamate as well as toward a variety of additional neurotoxins. Conversely, it was determined if inhibitors of oxytosis, a well-defined oxidative stress pathway, also protect cells from the neurotoxins. It is shown that both glutamate and amyloid resistant cells are cross resistant to most of the other toxins or toxic conditions, while inhibitors of oxytosis protect from glutathione and cystine depletion and H2O2 toxicity, but not from the toxic effects of nitric oxide, rotenone, arsenite or cisplatin. It is concluded that while there is a great deal of cross-resistance to neurotoxins, the components of the cell death pathway which has been defined for oxytosis are not used by many of the neurotoxins.
Inhibition of Rumen Cellulose Digestion by Extracts of Sericea Lespedeza (1967)

Cellulose hydrolysis was found to be inhibited by a purified preparation of a waterextractable inhibitor from fresh sericea forage. This inhibition was obtained under rumen conditions as well as in in vitro trials. When casein was added to the cellulose-rumen fluid mixture containing PSI, considerable protection of activity was afforded to the cellulose degrading system; but at high levels of inhibitor, casein had no effect. While fine chopping of the fresh material or drying of the forage reduced the amount of extractable inhibitor to a low level, the digestibility of the cellulose of the dry form was not higher than the fresh forage.
Preparation and characterization of a novel nanobody against T-cell immunoglobulin and mucin-3 (TIM-3). (2016)

Finally, we successfully prepared a functional anti-humanTIM-3 specific nanobody with a high affinity and an anti-proliferative activity on an AML cell line in vitro.
Effect of von Willebrand Factor Coexpression on the Synthesis and Secretion of Factor VIII in Chinese Hamster Ovary Cells (1989)

In plasma, antihemophilic factor (factor VIII) exists as a 200-kilodalton heavy-chain polypeptide in a metal ion association with an 80-kilodalton light-chain polypeptide. This complex is bound by hydrophobic and hydrophilic interactions to a large multimeric glycoprotein, von Willebrand factor (vWF). Accumulation of secreted human factor VIII activity expressed in Chinese hamster ovary cells requires the addition of serum in the growth medium, which provides vWF. Here we report that coexpression of vWF with factor VIII in Chinese hamster ovary cells resulted in increased stable accumulation of factor VIII activity in the absence of serum in the growth medium. In the coexpressing cells, the vWF cDNA transcription unit was transcribed to yield mRNA which was efficiently translated. vWF was properly processed and secreted to yield disulfide-bonded high-molecular-weight multimers similar to those observed in vWF secreted from human endothelial cells. Nuclear run-on assays showed that the factor VIII gene was transcribed at a level similar to that of the vWF gene, but the mRNA did not accumulate to high levels in the cytoplasm. In addition, although the translation efficiency of the factor VIII mRNA was similar to that of vWF, the processing and secretion of the factor VIII primary translation product was dramatically reduced compared with vWF. These results demonstrate that in Chinese hamster ovary cells both factor VIII mRNA accumulation and the processing and secretion of the primary factor VIII translation product are inefficient processes.
Very high efficiency VLSI chip-pair for full search block matching with fractional precision (2003)

VLSI architecture design and implementation of a chip pair for the motion compensation full search block matching algorithm are described. This pair of ASICs (application-specific integrated circuits) is motivated by the intensive computational demands for performing motion compensation in real time. They have been developed to calculate fractional motion vectors with quarter-pel precision. The VLSI architecture is based on some special data-flow designs that allow sequential inputs but perform parallel processing with 100% efficiency for integer motion vector estimation and nearly 100% for fractional motion vector estimation. The chip-pair design has been laid out and simulated using a silicon compiler tool, and the chip statistics are summarized. Testing circuitry is included to increase the observability of the chips.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
RET Gene Analysis in Patients with Medullary Thyroid Carcinoma (2016)

These results underline the importance of the genetic background of family members of any patient with MTC.
Azacitidine and decitabine have different mechanisms of action in non-small cell lung cancer cell lines (2010)

Azacitidine (AZA) and decitabine (DAC) are cytidine azanucleoside analogs with clinical activity in myelodysplastic syndromes (MDS) and potential activity in solid tumors. To better understand the mechanism of action of these drugs, we examined the effects of AZA and DAC in a panel of non-small cell lung cancer (NSCLC) cell lines. Of 5 NSCLC lines tested in a cell viability assay, all were sensitive to AZA (EC<sub>50</sub> of 1.8-10.5 µM), while only H1299 cells were equally sensitive to DAC (EC<sub>50</sub> of 5.1 µM). In the relatively DAC-insensitive cell line A549, both AZA and DAC caused DNA methyltransferase I depletion and DNA hypomethylation; however, only AZA significantly induced markers of DNA damage and apoptosis, suggesting that mechanisms in addition to, or other than, DNA hypomethylation are important for AZA-induced cell death. Cell cycle analysis indicated that AZA induced an accumulation of cells in sub-G1 phase, whereas DAC mainly caused an increase of cells in G2/M. Gene expression analysis of AZA- and DAC-treated cells revealed strikingly different profiles, with many genes distinctly regulated by each drug. In summary, while both AZA and DAC caused DNA hypomethylation, distinct effects were demonstrated on regulation of gene expression, cell cycle, DNA damage, and apoptosis.
Loss of nuclear localization of TET2 in colorectal cancer (2016)

5-Hydroxymethylcytosine (5hmC) is lost in multiple human cancers, including colorectal cancer (CRC). Decreased ten-eleven translocation 1 (TET1) messenger RNA (mRNA), but not other two TET family members, has been observed in the colorectal cancer and is crucial for colorectal cancer initiation. Here, we show that nuclear localization of TET2 was lost in a significant portion of CRC tissues, in association with metastasis. In CRC cells, nuclear expression of TET2 were absent but not TET3. Nuclear export inhibitor can increase the 5hmC level in CRC cells, probably through regulating TET2. Our results indicate a new mechanism of TET2 dysregulation in colorectal cancer.
Synthesis and Structure-Activity Relationships of Oxamic Acid and Acetic Acid Derivatives Related to L-Thyronine (1995)

Aryloxamic acids 7 and 23, (arylamino)acetic acids 29, arylpropionic acids 33, arylthioacetic acids 37, and (aryloxy)acetic acid 41 related to L-triiodothyronine (L-T3) were prepared and tested in vitro for binding to the rat liver nuclear L-T3 receptor and the rat membrane L-T3 receptor. The structure-activity relationships for these compounds are described, with 7f, 23a, 29c, 33a, 37b, and 41 showing excellent potency (IC50's of 0.19, 0.16, 1.1, 0.11, 3.5, and 0.10 nM, respectively) to the nuclear receptor and significantly lower binding affinity to the membrane receptor (IC50's > 5 microM). Some of these compounds, especially in the oxamic acid series 7 and 23, showed an unprecedented potency for methyl-substituted derivatives such as 7f and 23a. Compounds 7f and 23a showed good lipid lowering effects in rats with ED50's of 20 and 5 micrograms/kg po, respectively, and a lack of cardiac side effects in rats at doses as high as 10 and 25 mg/kg po, respectively.
Expression of the C‐erbB‐3 protein in gastrointestinal tract tumours determined by monoclonal antibody RTJ1 (1993)

We have examined the expression of the c-erbB-3 protein in a wide range of tumours of the gastrointestinal (GI) tract using immunocytochemical staining. Two antibodies were employed, a polyclonal antibody, 49.3, and a new monoclonal antibody, RTJ1, both raised to a synthetic peptide from the cytoplasmic domain of the human c-erbB-3 protein. The antibodies recognize c-erbB-3 by immunoprecipitation and Western blotting of lysate prepared from a cell line engineered to overexpress the protein. Both antibodies also detect expression of the protein in formalin-fixed, paraffin-embedded human tissues. The RTJ1 monoclonal antibody gave superior staining, showing lower background and more pronounced cell surface immunoreactivity. The c-erbB-3 protein was found in normal epithelial cells throughout the GI tract, in squamous epithelium of the oropharanyx and oesophagus, in the parietal cells of the stomach, and in the surface enterocytes of the small and large bowel. Seventy-six tumours arising at these sites were examined for c-erbB-3 protein expression. Widely varying levels of expression were seen, from absent to intense staining with cell membrane accentuation.
Laparoscopic surgery using spinal anesthesia. (2008)

Laparoscopic surgery done with the patient under spinal anesthesia has several advantages over laparoscopic surgery done with the patient under general anesthesia.
Early Error Detection and Classification in Data Transfer Scheduling (2009)

Data transfer in distributed environment is prone to frequent failures resulting from back-end system level problems, like connectivity failure which is technically untraceable by users.Error messages are not logged efficiently, and sometimes are not relevant/useful from users' point-of-view.Our study explores the possibility of an efficient error detection and reporting system for such environments.Besides, early error detection and error classification have great importance in organizing data placement jobs.It is necessary to have well defined error detection and error reporting methods to increase the usability and serviceability of existing data transfer protocols and data management systems. Prior knowledge about the environment and awareness of the actual reason behind a failure would enable data placement scheduler to make better and accurate decisions.We investigate the applicability of proposed early error detection and error classification techniques to improve arrangement of data placement jobs and to enhance decision making of data placement schedulers.
Lactose-Inducible System for Metabolic Engineering of Clostridium ljungdahlii (2014)

The development of tools for genetic manipulation of Clostridium ljungdahlii has increased its attractiveness as a chassis for autotrophic production of organic commodities and biofuels from syngas and microbial electrosynthesis and established it as a model organism for the study of the basic physiology of acetogenesis. In an attempt to expand the genetic toolbox for C. ljungdahlii, the possibility of adapting a lactose-inducible system for gene expression, previously reported for Clostridium perfringens, was investigated. The plasmid pAH2, originally developed for C. perfringens with a gusA reporter gene, functioned as an effective lactose-inducible system in C. ljungdahlii. Lactose induction of C. ljungdahlii containing pB1, in which the gene for the aldehyde/alcohol dehydrogenase AdhE1 was downstream of the lactose-inducible promoter, increased expression of adhE1 30-fold over the wild-type level, increasing ethanol production 1.5-fold, with a corresponding decrease in acetate production. Lactose-inducible expression of adhE1 in a strain in which adhE1 and the adhE1 homolog adhE2 had been deleted from the chromosome restored ethanol production to levels comparable to those in the wild-type strain. Inducing expression of adhE2 similarly failed to restore ethanol production, suggesting that adhE1 is the homolog responsible for ethanol production. Lactose-inducible expression of the four heterologous genes necessary to convert acetyl coenzyme A (acetyl-CoA) to acetone diverted ca. 60% of carbon flow to acetone production during growth on fructose, and 25% of carbon flow went to acetone when carbon monoxide was the electron donor. These studies demonstrate that the lactose-inducible system described here will be useful for redirecting carbon and electron flow for the biosynthesis of products more valuable than acetate. Furthermore, this tool should aid in optimizing microbial electrosynthesis and for basic studies on the physiology of acetogenesis.
Sortase-catalyzed transformations that improve the properties of cytokines (2011)

Recombinant protein therapeutics often suffer from short circulating half-life and poor stability, necessitating multiple injections and resulting in limited shelf-life. Conjugation to polyethylene glycol chains (PEG) extends the circulatory half-life of many proteins, but the methods for attachment often lack specificity, resulting in loss of biological activity. Using four-helix bundle cytokines as an example, we present a general platform that uses sortase-mediated transpeptidation to facilitate site-specific attachment of PEG to extend cytokine half-life with full retention of biological activity. Covalently joining the N and C termini of proteins to obtain circular polypeptides, again executed using sortase, increases thermal stability. We combined both PEGylation and circularization by exploiting two distinct sortase enzymes and the use of a molecular suture that allows both site-specific PEGylation and covalent closure. The method developed is general, uses a set of easily accessible reagents, and should be applicable to a wide variety of proteins, provided that their termini are not involved in receptor binding or function.
Transplantation of purified hematopoietic stem cells: requirements for overcoming the barriers of allogeneic engraftment. (1996)

Allogeneic bone marrow transplantation currently plays a critical role in the treatment of leukemias and inherited disorders of hematopoiesis, and it shows great promise for the treatment of numerous other diseases. The problems of graft-vs-host disease (GVHD) and failure to engraft, however, remain formidable obstacles to the widespread use of this therapy. Successful transplantation of purified populations of hematopoietic stem cells (HSCs) can theoretically avoid the problem of GVHD, since purified HSCs lack the mature elements that allow the graft to mount a response against the host. In previous studies from our laboratory, a population of purified HSCs (Thy-1loLin-/loSca-1+) was isolated from mouse bone marrow (BM). These cells represent approximately 0.05% of BM cells and are capable of self-renewal and long-term reconstitution of all blood lineages. Here we report long-term engraftment of these purified HSCs transplanted in mice across successively more difficult allogeneic-histocompatibility barriers. Transplantation of purified HSCs were quantitatively compared with whole bone marrow (WBM) grafts containing equivalent numbers of stem cells. The mouse strain combinations tested were parent transplanted into F1 (Hh disparate), minor histocompatibility complex (mHC), and major histocompatibility complex (MHC) plus mHC disparities. One of the recipient strains studied for MHC-disparate transplantations was that of spontaneously autoimmune diabetic mice. Recipient mice were administered lethal doses of whole-body irradiation in the presence or absence of antibodies directed against natural killer (NK) cell-associated determinants and/or monoclonal antibodies against the CD4+ T cell subset. We find that as the barrier to transplantation increases, greater numbers of HSCs are required for radioprotection and engraftment. In all cases, stable hematopoietic chimeras were generated with HSCs alone, but 10-60 times the number of HSCs was required for radioprotection of mice transplanted across allogeneic or semiallogeneic disparities as compared to Ly-5 congenic differences. Furthermore, we demonstrate a clear advantage of WBM vs HSCs with regard to tha ability to engraft [corrected]. Chimeric mice showed no symptoms of GVHD, and their T cells were unable to induce GVHD in neonatal mice expressing H-2 antigens of donor and host. These data confirm that a cell population resident in WBM and distinct from purified stem cells is important in facilitating hematopoietic engraftment, in this case, of purified allogeneic HSCs. The differences in engraftment between WBM and HSCs could be reduced significantly by the addition of antibodies directed against NK determinants to the host preparative regimen. Similarly, since antibodies directed against host NK-associated antigens can reduce the barrier to allogeneic HSC engraftment, an interaction between the facilitating population within donated WBM and a resistant host population with NK determinants is implied.