gebhart/patrepeval huggingface dataset:
CD44 Interaction with Na+-H+ Exchanger (NHE1) Creates Acidic Microenvironments Leading to Hyaluronidase-2 and Cathepsin B Activation and Breast Tumor Cell Invasion (2004)

We have explored CD44 (a hyaluronan (HA) receptor) interaction with a Na(+)-H(+) exchanger (NHE1) and hyaluronidase-2 (Hyal-2) during HA-induced cellular signaling in human breast tumor cells (MDA-MB-231 cell line). Immunological analyses demonstrate that CD44s (standard form) and two signaling molecules (NHE1 and Hyal-2) are closely associated in a complex in MDA-MB-231 cells. These three proteins are also significantly enriched in cholesterol and ganglioside-containing lipid rafts, characterized as caveolin and flotillin-rich plasma membrane microdomains. The binding of HA to CD44 activates Na(+)-H(+) exchange activity which, in turn, promotes intracellular acidification and creates an acidic extracellular matrix environment. This leads to Hyal-2-mediated HA catabolism, HA modification, and cysteine proteinase (cathepsin B) activation resulting in breast tumor cell invasion. In addition, we have observed the following: (i) HA/CD44-activated Rho kinase (ROK) mediates NHE1 phosphorylation and activity, and (ii) inhibition of ROK or NHE1 activity (by treating cells with a ROK inhibitor, Y27632, or NHE1 blocker, S-(N-ethyl-N-isopropyl) amiloride, respectively) blocks NHE1 phosphorylation/Na(+)-H(+) exchange activity, reduces intracellular acidification, eliminates the acidic environment in the extracellular matrix, and suppresses breast tumor-specific behaviors (e.g. Hyal-2-mediated HA modification, cathepsin B activation, and tumor cell invasion). Finally, down-regulation of CD44 or Hyal-2 expression (by treating cells with CD44 or Hyal-2-specific small interfering RNAs) not only inhibits HA-mediated CD44 signaling (e.g. ROK-mediated Na(+)-H(+) exchanger reaction and cellular pH changes) but also impairs oncogenic events (e.g. Hyal-2 activity, hyaluronan modification, cathepsin B activation, and tumor cell invasion). Taken together, our results suggest that CD44 interaction with a ROK-activated NHE1 (a Na(+)-H(+) exchanger) in cholesterol/ganglioside-containing lipid rafts plays a pivotal role in promoting intracellular/extracellular acidification required for Hyal-2 and cysteine proteinase-mediated matrix degradation and breast cancer progression.
Scientific Opinion of the Panel on Food Additives and Nutrient Sources added to Food (ANS) (2009)

SUMMARY Following a request from the Commission to the European Food Safety Authority, the Scientific Panel on Additives and Nutrient Sources added to Food was asked to provide a scientific opinion on the safety of inositol hexanicotinate (inositol hexaniacinate) added for nutritional purposes as a source of niacin (vitamin B3) in food supplements and on the bioavailability of nicotinic acid from this source. The present opinion deals only with the safety of inositol hexanicotinate as a source of nicotinic acid, one of the vitamers of niacin (vitamin B3), intended for the general population, to be added to food supplements and the bioavailability of nicotinic acid from this source. The safety of nicotinic acid itself, in terms of amounts that may be consumed, is outside the remit of this Panel. 1
Genomic Sequencing and Comparative Analysis of Epstein-Barr Virus Genome Isolated from Primary Nasopharyngeal Carcinoma Biopsy (2012)

Whether certain Epstein-Barr virus (EBV) strains are associated with pathogenesis of nasopharyngeal carcinoma (NPC) is still an unresolved question. In the present study, EBV genome contained in a primary NPC tumor biopsy was amplified by Polymerase Chain Reaction (PCR), and sequenced using next-generation (Illumina) and conventional dideoxy-DNA sequencing. The EBV genome, designated HKNPC1 (Genbank accession number JQ009376) is a type 1 EBV of approximately 171.5 kb. The virus appears to be a uniform strain in line with accepted monoclonal nature of EBV in NPC but is heterogeneous at 172 nucleotide positions. Phylogenetic analysis with the four published EBV strains, B95-8, AG876, GD1, and GD2, indicated HKNPC1 was more closely related to the Chinese NPC patient-derived strains, GD1 and GD2. HKNPC1 contains 1,589 single nucleotide variations (SNVs) and 132 insertions or deletions (indels) in comparison to the reference EBV sequence (accession number NC007605). When compared to AG876, a strain derived from Ghanaian Burkitt's lymphoma, we found 322 SNVs, of which 76 were non-synonymous SNVs and were shared amongst the Chinese GD1, GD2 and HKNPC1 isolates. We observed 88 non-synonymous SNVs shared only by HKNPC1 and GD2, the only other NPC tumor-derived strain reported thus far. Non-synonymous SNVs were mainly found in the latent, tegument and glycoprotein genes. The same point mutations were found in glycoprotein (BLLF1 and BALF4) genes of GD1, GD2 and HKNPC1 strains and might affect cell type specific binding. Variations in LMP1 and EBNA3B epitopes and mutations in Cp (11404 C>T) and Qp (50134 G>C) found in GD1, GD2 and HKNPC1 could potentially affect CD8(+) T cell recognition and latent gene expression pattern in NPC, respectively. In conclusion, we showed that whole genome sequencing of EBV in NPC may facilitate discovery of previously unknown variations of pathogenic significance.
An efficient k-means clustering algorithm: analysis and implementation (2002)

In k-means clustering, we are given a set of n data points in d-dimensional space R/sup d/ and an integer k and the problem is to determine a set of k points in Rd, called centers, so as to minimize the mean squared distance from each data point to its nearest center. A popular heuristic for k-means clustering is Lloyd's (1982) algorithm. We present a simple and efficient implementation of Lloyd's k-means clustering algorithm, which we call the filtering algorithm. This algorithm is easy to implement, requiring a kd-tree as the only major data structure. We establish the practical efficiency of the filtering algorithm in two ways. First, we present a data-sensitive analysis of the algorithm's running time, which shows that the algorithm runs faster as the separation between clusters increases. Second, we present a number of empirical studies both on synthetically generated data and on real data sets from applications in color quantization, data compression, and image segmentation.
Identification and characterization of clustered genes for thermostable xylan-degrading enzymes, beta-xylosidase and xylanase, of Bacillus stearothermophilus 21 (1994)

Bacillus stearothermophilus 21 is a gram-positive, facultative thermophilic aerobe that can utilize xylan as a sole source of carbon. We isolated this strain from soil, purified its extracellular xylanase and beta-xylosidase, and analyzed the two-step degradation of xylan by these enzymes (T. Nanmori, T. Watanabe, R. Shinke, A. Kohno, and Y. Kawamura, J. Bacteriol. 172:6669-6672, 1990). An Escherichia coli transformant carrying a 4.2-kbp chromosomal segment of this bacterium as a recombinant plasmid was isolated. It excreted active beta-xylosidase and xylanase into the culture medium. The plasmid was introduced into UV-sensitive E. coli CSR603, and its protein products were analyzed by the maxicell method. Proteins harboring beta-xylosidase and xylanase activities were identified, and their molecular masses were estimated by sodium dodecyl sulfate-polyarylamide gel electrophoresis to be 75 and 40 kDa, respectively. The values were identical to those of proteins prepared from cells of B. stearothermophilus 21. The genes for both enzymes were encoded in a 3.4-kbp PstI fragment derived from the 4.2-kbp chromosomal segment. The nucleotide sequence of the 4.2-kbp segment was accordingly determined. The beta-xylosidase gene (xylA) is located upstream of the xylanase gene (xynA) with a possible promoter and a Shine-Dalgarno sequence. The latter gene is preceded by two possible promoters and a Shine-Dalgarno sequence that are located within the 3'-terminal coding region of the former. The two genes thus appear to be, at least partly, expressed independently, which was experimentally confirmed in E. coli by deletion analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Geometric Tools for Computer Graphics (2002)

From the Publisher:
Do you spend too much time creating the building blocks of your graphics applications or finding and correcting errors? Geometric Tools for Computer Graphics is an extensive, conveniently organized collection of proven solutions to fundamental problems that you'd rather not solve over and over again, including building primitives, distance calculation, approximation, containment, decomposition, intersection determination, separation, and more.
If you have a mathematics degree, this book will save you time and trouble. If you don't, it will help you achieve things you may feel are out of your reach. Inside, each problem is clearly stated and diagrammed, and the fully detailed solutions are presented in easy-to-understand pseudocode. You also get the mathematics and geometry background needed to make optimal use of the solutions, as well as an abundance of reference material contained in a series of appendices.
KEY FEATURES: * Filled with robust, thoroughly tested solutions that will save you time and help you avoid costly errors.
* Covers problems relevant for both 2D and 3D graphics programming.
* Presents each problem and solution in stand-alone form allowing you the option of reading only those entries that matter to you.
* Provides the math and geometry background you need to understand the solutions and put them to work.
* Clearly diagrams each problem and presents solutions in easy-to-understand pseudocode.
* Resources associated with the book are available at the companion Web site.
Author Biography: Philip Schneider leads a modeling and dynamic simulation software group at Walt Disney Feature Animation. Prior to that, his work at Apple and Digital Equipment Corporation in 3D graphics ranged from low-level interfaces to graphics libraries and interactive applications. He holds an M.S. in Computer Science from the University of Washington.
Dave Eberly is the president of Magic Software, Inc., a company known for its free source code and documentation for computer graphics, image analysis, and numerical methods. Previously, he was the director of engineering at Numerical Design Limited, the company responsible for the real-time 3D game engine, NetImmerse. His background includes a B.A. in mathematics from Bloomsburg University, M.S. and Ph.D. degrees in mathematics from the University of Colorado at Boulder, and M.S. and Ph.D. degrees in computer science from the University of North Carolina at Chapel Hill. Dave is author of 3D Game Engine Design, co-author with Philip Schneider of Geometric Tools for Computer Graphics, and author of the forthcoming Game Physics (Spring 2003).
A Comparative Trial of Rhesus Monkey (RRV-1) and Bovine (RIT 4237) Oral Rotavirus Vaccines in Young Children (1986)

Heterologous live, oral rotavirus vaccines of rhesus monkey (RRV-1) and bovine (RIT 4237) origin were tested for immunogenicity, excretion of virus, and clinical reactions in six- to eight-month-old infants. Antibody response, indicating infection with the vaccine virus, was detected in 21 (88%) of 24 children receiving the RRV-1 vaccine and in 18 (75%) of 24 receiving the RIT 4237 vaccine. Excretion of virus in the stools within one week after vaccination was demonstrable in 84% of the RRV-1 and in 21% of the RIT 4237 vaccinees. RRV-1 vaccination was associated with a febrile response (over 38 C) that clustered on days 3 or 4 postvaccination in 64% of the recipient children. In addition, 20% of the RRV-1 vaccinees had watery stools on days 4 or 5. Fever on days 3 and 4 and loose stools were not seen in the RIT 4237 vaccinees. We concluded that in young children the RRV-1 (rhesus monkey) rotavirus vaccine is more immunogenic than the RIT 4237 (bovine) rotavirus vaccine, but vaccination with RRV-1 is associated with significant adverse reactions.
Correlation of Structural Alterations in Bovine Fibrinogen with Loss of Clotting Properties after Gamma Irradiation (1972)

Hemalata N. Kamat, G. B. Nadkarni, Correlation of Structural Alterations in Bovine Fibrinogen with Loss of Clotting Properties after Gamma Irradiation, Radiation Research, Vol. 49, No. 2 (Feb., 1972), pp. 381-389
Processing of hepatitis B virus surface antigen expressed by recombinant Oka varicella vaccine virus (1992)

We have constructed a recombinant Oka varicella vaccine virus expressing hepatitis B virus (HBV) surface antigen (HBsAg). HBsAg was synthesized as 26K and 30K proteins in infected cells and secreted into the culture supernatant as 30K and 35K proteins. Inhibitors and glycosidase treatments, and pulse-chase labelling experiments, revealed the glycosylation process of HBsAg. The latter was synthesized as a non-glycosylated 26K protein and subjected to N-linked glycosylation to form a 30K protein with high mannose glycans. Three species of dimers composed of 26K and 30K subunits were then formed with disulphide bonds. Both subunits of the dimers were further subjected to O-linked glycosylation and conversion from high mannose glycans to complex glycans followed by sialylation. Three species of dimers composed of 30K and 35K subunits were secreted into the culture supernatant as HBsAg particles. HBsAg was synthesized, glycosylated with both N- and O-linked glycans, sialylated, and then secreted into the culture supernatant within 1 h. These modifications of HBsAg by glycans might stabilize its structure and enhance its immunogenicity as a live HBV vaccine.
Bipolar Surface Electrical Stimulation of the Vertebrate Retina (1994)

Multifocal electrical stimulation of the retina might be a viable approach to provide some vision to patients who have profound visual loss due to outer retinal degenerations.
Humoral response to p53 in human colorectal tumors: A prospective study of 1,209 patients (2001)

p53 Antibodies (p53-Abs) have been detected in the serum of a proportion of colorectal cancer (CRC) patients. It is not yet known at which stage during colorectal tumor progression p53-Abs appear in the serum. The utility of these antibodies as markers for CRC prognosis remains to be clarified. Using a quantitative enzyme-linked immunosorbent assay, we analyzed serum samples from 998 CRC patients and from 211 patients with polyp. Levels of p53-Abs were defined as negative (<10 U/microL), low (10-76 U/microL) and high (>76 U/microL). Overall, 13.0% of CRC patients and less than 1% of polyp patients had increased serum p53-Ab levels. High p53-Ab levels were only seen in patients with invasive carcinomas. The parameters that were significantly and independently associated with a greater frequency of high p53-Ab levels were the left colon (odds ratio [OR] = 3.4; 95% CI = 1.1-10.5), the rectum (OR = 2.9; 95% CI, 1.0-8.8) and advanced lymph node metastasis (OR = 4.6; 95% CI, 2.2-9.6). In univariate analysis, patients with high p53-Ab levels had a shorter survival times than did those without (p = 0.007). However, the significant effect disappeared in a Cox regression model adjusting for sex, age, tumor location, carcinoembryonic antigen levels, gross findings, histologic grade, mucin production and TNM stage. Thus, autoantibodies against p53 occur with tumor progression in multistep colorectal carcinogenesis and increase with advanced node metastasis. Furthermore, the seemingly adverse effect of high p53-Ab levels on the survival of CRC patients may be explained by other prognostic factors.
Lack of miscoding properties of 7-(2-oxoethyl)guanine, the major vinyl chloride-DNA adduct. (1985)

Chloroethylene oxide, an ultimate carcinogenic metabolite of vinyl chloride, was reacted with poly(deoxyguanylate-deoxycytidylate); the nucleic acid base adducts, 7-(2-oxoethyl)guanine and 3,N4-ethenocytosine, were analyzed by reverse-phase high-performance liquid chromatography. Chloroethylene oxide-modified poly(deoxyguanylate-deoxycytidylate) was assayed as template in a replication fidelity assay with Escherichia coli DNA polymerase I, and the newly synthesized product was subjected to nearest-neighbor analysis. Misincorporation rates of deoxyadenosine monophosphate and thymidine monophosphate were found to increase with the level of template modification. About 80% of the mispairing events were located opposite minor cytosine lesions. 7-(2-Oxoethyl)guanine, the major adduct identified (greater than 98% of the adducts), did not miscode for either thymine or adenine, failing to support an earlier hypothesis that the cyclic hemiacetal form, O6,7-(1'-hydroxyethano)guanine, could, by analogy with O6-methyl- and O6-ethylguanine, simulate adenine. Our results indicate that direct miscoding of 7-(2-oxoethyl)-guanine may contribute only slightly to the induction of mutations by chloroethylene oxide or vinyl chloride.
Properties of photonic crystal fiber and the effective index model (1998)

We report the waveguiding properties of a new type of low-loss optical waveguide. The photonic crystal fiber can be engineered to support only the fundamental guided mode at every wavelength within the transparency window of silica. Experimentally, a robust single mode has been observed over a wavelength range from 337 nm to beyond 1550 nm (restricted only by available wavelength sources). By studying the number of guided modes for fibers with different parameters and the use of an effective index model, we are able to quantify the requirements for monomode operation. The requirements are independent of the scale of the fiber for sufficiently short wavelengths. Further support for the predictions of the effective index model is given by the variation of the spot size with wavelength.
Inhibition of the CD8+ T cell-mediated cytotoxicity reaction by hypericin: potential for treatment of T cell-mediated diseases (2000)

The cytotoxicity reaction of murine CD8 T lymphocytes has been found to be strongly inhibited by nanomolar concentrations of hypericin, a lipophilic dianthraquinone with photodynamic properties. Cytotoxic T lymphocyte (CTL)-induced target cell apoptosis, as well as exocytosis of cytolytic granules from these cells, were ablated by hypericin, administered at the onset of the reaction, without affecting CTL viability. The inhibition of cytolysis occurred without the light irradiation which is essential for photosensitization. The findings suggest that the action of hypericin targets the effector CTL; however, apoptosis induced in murine L-cells with recombinant tumor necrosis factor (TNF)-alpha was also prevented by hypericin. Since hypericin is a known inhibitor of protein kinase C, MAP kinase and at least one other tyrosine kinase, this inhibitory activity could play a role in the down-modulation of CTL-induced cytotoxicity. Furthermore, our studies show that the action of hypericin induces rapid dephosphorylation of phospholipids associated with low-density membranes in CTL, but not with membranes of the cytotoxic granules. The ability of hypericin to interfere with cytotoxicity may render it useful in the treatment of T cell-mediated diseases.
Second Generation “Peptoid” CCK-B Receptor Antagonists:  Identification and Development ofN-(Adamantyloxycarbonyl)-α-methyl-(R)-tryptophan Derivative (CI-1015) with an Improved Pharmacokinetic Profile (1998)

We have previously described the design and development of CI-988, a peptoid analogue of CCK-4 with excellent binding affinity and selectivity for the CCK-B receptor. Due to its anxiolytic profile in animal models of anxiety, this compound was developed as a clinical candidate. However, during its development, it was determined that CI-988 had low bioavailability in both rodent and nonrodent species. In the clinic, it was further established that CI-988 had poor bioavailability. Thus, there was a need to identify an analogue with an improved pharmacokinetic (PK) profile. The poor bioavailability was attributed to poor absorption and efficient hepatic extraction. We envisaged that reducing the molecular weight of the parent compound (5, MW = 614) would lead to better absorption. Thus, we synthesized a series of analogues in which the key alpha-methyltryptophan and adamantyloxycarbonyl moieties, required for receptor binding, were kept intact and the C-terminus was extensively modified. This SAR study led to the identification of tricyclo[3.3.1.1(3,7)]dec-2-yl [1S-[1 alpha(S*)2 beta]-[2-[(2-hydroxycyclohexyl)amino]-1-(1H-indol-3- ylmethyl)-1-methyl-2-oxoethyl]carbamate (CI-1015, 31) with binding affinities of 3.0 and 2900 nM for the CCK-B and CCK-A receptors, respectively. The compound showed CCK-B antagonist profile in the rat ventromedial hypothalamus assay with a Ke of 34 nM. It also showed an anxiolytic like profile orally in a standard anxiety paradigm (X-maze) with a minimum effective dose (MED) of 0.1 microgram/kg. Although the compound is less water soluble than CI-988, oral bioavailability in rat was improved nearly 10 times relative to CI-988 when dosed in HP beta CD. The blood-brain permeability of CI-1015 (31) was also enhanced relative to CI-988 (5). On the basis of the overall improved pharmacokinetic profile as well as enhanced brain penetration, CI-1015 (31) was chosen as a development candidate.
Building Microbial Forensics as a Response to Bioterrorism (2003)

Combating bioterrorism is a challenge to all of us. To be proactive, the U.S. Government has formalized the discipline of "microbial forensics" to deter and attribute perpetrators of such acts. This Policy Forum describes the foundations of the microbial forensics program: the creation of a national bioforensics laboratory, a partnership laboratory network, and a peer-consensus scientific working group and the promulgation of quality assurance guidelines.
Immuno-PET of Cancer: A Revival of Antibody Imaging (2011)

See page [1173][1] With the identification of tumor-associated antigens more than 30 y ago and the development of hybridoma technology in 1975, investigators realized that Paul Ehrlich's vision to effectively target drugs to diseased tissues could be tested. It was shown that monoclonal antibodies
Deep brain stimulation activation volumes and their association with neurophysiological mapping and therapeutic outcomes (2008)

Our results are consistent with previous studies suggesting that therapeutic benefit is associated with electrode contacts near the dorsal border of the STN, and provide quantitative estimates of the electrical spread of the stimulation in a clinically relevant context.
Verification of arithmetic circuits with binary moment diagrams (1995)

Article Free Access Share on Verification of arithmetic circuits with binary moment diagrams Authors: Randal E. Bryant Carnegie Mellon University, Pittsburgh, PA Carnegie Mellon University, Pittsburgh, PAView Profile , Yirng-An Chen Carnegie Mellon University, Pittsburgh, PA Carnegie Mellon University, Pittsburgh, PAView Profile Authors Info & Claims DAC '95: Proceedings of the 32nd annual ACM/IEEE Design Automation ConferenceJanuary 1995 Pages 535–541https://doi.org/10.1145/217474.217583Published:01 January 1995Publication History 229citation538DownloadsMetricsTotal Citations229Total Downloads538Last 12 Months50Last 6 weeks13 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF