gebhart/patrepeval huggingface dataset:
Enhancing the Effect of THERATOPE STn-KLH Cancer Vaccine in Patients with Metastatic Breast Cancer by Pretreatment with Low-Dose Intravenous Cyclophosphamide (1996)

THERATOPE (Biomira Inc., Edmonton, AB, Canada) STn-KLH cancer vaccine induces strong antibody titers against both the synthetic STn epitope and against a natural mucin, OSM, which expresses STn-like epitopes. In prospective, randomized studies in patients with metastatic breast cancer treated at two cancer centers, the effect of different low-dose, immunomodulatory cyclophosphamide (cyclo) pretreatments on the response to THERATOPE STn-KLH was compared. Patients were randomized to receive either intravenous cyclo 300 mg/m2 on day -3, or oral cyclo 50 mg daily from days -14 to -3 inclusive, or no cyclo, before THERATOPE treatments. The anti-STn and anti-OSM antibody titers were higher in the patients who received cyclo intravenously before THERATOPE. Patients treated with cyclo intravenously and THERATOPE STn-KLH cancer vaccine lived significantly longer (projected median survival of 19.7 months versus actual median survival of 12.6 months, p = 0.0176) than those treated with the same STn vaccine with oral or no cyclo. Although it is not clear how the anti-STn antibody response modifies tumor biology, we noted that patients in the intravenously administered cyclo group had a lower percentage of patients showing progressive disease at 9 weeks, and that there was an inverse correlation between serum anti-STN antibody titer and growth of measurable tumors. There was no correlation between tumor growth and anti-KLH antibody titers. These data are consistent with a therapeutic effect of THERATOPE STn-KLH cancer vaccine and support development of a phase III study to explore this further.
The fatty acid composition of seed oils from ten plant families with particular reference to cyclopropene and dihydrosterculic acids (1980)

Abstract Oil contents and fatty acid compositions of 40 seed oils of the plant families Elaecarpaceae, Thymelaeceae, Malvaceae, Sterculiaceae (order Malvales); Anacardiaceae, Celestraceae, Sapindaceae (Sapindales); Ebenaceae, Sapotaceae (Ebenales) and Rhamnaceae (Rhamnales) are presented. Cyclopropene fatty acids (CPFA) occur in two families in the order malvales not hitherto assayed. CPFA contents of seed oils of 12 Australian and Pacific species of Malvaceae and Sterculiaceae are given. CPFA occur randomly in small amounts in at least six families not in the order Malvales. Dehydrosterculic acid (DHS) occurs in small amounts in many species of Anacardiaceae, Celestraceae, Elaeocarpaceae, Malvaceae, Sapindaceae, Sapotaceae and Sterculiaceae. Linoleic acid was predominant in 28 of 40 seed oils, being as high as 63.9% in two species. The sum of 18:1 and 18:2 esters exceeded 70% in 20 oils.
Conserved sequence and structure association motifs in antibody-protein and antibody-hapten complexes (2004)

In this paper, we present the association requirements across a wide variety of antibody-antigen complexes. Phylogenetic analysis clearly indicates the representative nature of our structural dataset. Antigen molecules range from small-molecule haptens to complete protein structures. Common association motifs identified include five conserved tyrosine residues and a single conserved arginine residue from CDR-H3. Further, specificity is refined by a diverse array of antibody-antigen electrostatic interactions that maximize complex specificity. Through analysis of calculated pKa shifts on antigen binding, we find that these interactions are conserved at 23 alignment 'hot-spot' positions. Despite consistent roles in defining substrate specificity, 16 hot-spot positions are conserved less than 50% of the time. On the other hand, because of the conserved functional role of these positions, mutant screening at hot-spots is more likely to result in increased antigen specificity than elsewhere. Therefore, we believe these results should facilitate subsequent antibody design experimentation.
New implant for drainage in glaucoma. Clinical trial. (1969)

At present a trial is being undertaken using implants made of Transpex X sterilized by Ridley's caustic soda method (supplied by Rayner Optical Co., loo New Bond
Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30 (2007)

Increased expression of CD30 is associated with a variety of hematologic malignancies, including Hodgkin disease (HD) and anaplastic large cell lymphoma (ALCL). The anti-CD30 monoclonal antibody SGN-30 induces direct antitumor activity by promoting growth arrest and DNA fragmentation of CD30(+) tumor cells. In this study, we investigated the contributions of Fc-mediated effector cell functions to SGN-30 activity. We determined that antibody-dependent cellular phagocytosis, mediated by macrophages, to contribute significantly to antitumor activity in vitro. To delineate the identity of the host effector cells involved in mediating antitumor activity in vivo, we studied the effects of effector cell ablation in a disseminated model of HD (L540cy). Depletion of macrophages markedly reduced efficacy of SGN-30, demonstrating that macrophages contribute significantly to SGN-30 efficacy in this model. These findings may have implications for patient stratification or combination treatment strategies in clinical trials conducted with SGN-30 in HD and ALCL.
Time‐lapse seismic analysis of the North Sea Fulmar Field (1997)

PreviousNext No AccessSEG Technical Program Expanded Abstracts 1997Time‐lapse seismic analysis of the North Sea Fulmar FieldAuthors: David H. JohnstonRobert S. McKennyTucker D. BurkhartDavid H. JohnstonExxon Production Research Co., Robert S. McKennyExxon Production Research Co., and Tucker D. BurkhartPennsylvania State Universityhttps://doi.org/10.1190/1.1886159 SectionsAboutPDF/ePub ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InRedditEmail Permalink: https://doi.org/10.1190/1.1886159FiguresReferencesRelatedDetailsCited byFull Wavefield Inversion of Time-Lapse Data for Improved Imaging and Reservoir CharacterizationPartha Routh, Gopal Palacharla, Ivan Chikichev, and Spyros Lazaratos25 October 2012An approach to combined rock physics and seismic modelling of fluid substitution effects23 November 2002 | Geophysical Prospecting, Vol. 50, No. 2A finite‐difference injection approach to modeling seismic fluid flow monitoringJohan O. A. Robertsson, Sarah Ryan‐Grigor, Colin M. Sayers, and Chris H. Chapman7 February 2012 | GEOPHYSICS, Vol. 65, No. 3 SEG Technical Program Expanded Abstracts 1997ISSN (print):1052-3812 ISSN (online):1949-4645Copyright: 1997 Pages: 2067 publication data© 1997 Copyright © 1997 Society of Exploration GeophysicistsPublisher:Society of Exploration Geophysicists HistoryPublished Online: 10 Feb 2005 CITATION INFORMATION David H. Johnston, Robert S. McKenny, and Tucker D. Burkhart, (1997), "Time‐lapse seismic analysis of the North Sea Fulmar Field," SEG Technical Program Expanded Abstracts : 890-893. https://doi.org/10.1190/1.1886159 Plain-Language Summary PDF DownloadLoading ...
The Learning Curve for Adopting Hip Resurfacing Among Hip Specialists (2009)

Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
Epithelial cell kinase-B61: an autocrine loop modulating intestinal epithelial migration and barrier function (1997)

Epithelial cell kinase (Eck) is a member of a large family of receptor tyrosine kinases whose functions remain largely unknown. Expression and regulation of Eck and its cognate ligand B61 were analyzed in the human colonic adenocarcinoma cell line Caco-2. Immunocytochemical staining demonstrated coexpression of Eck and B61 in the same cells, suggestive of an autocrine loop. Eck levels were maximal in preconfluent cells. In contrast, B61 levels were barely detectable in preconfluent cells and increased progressively after the cells reached confluence. Caco-2 cells cultured in the presence of added B61 showed a significant reduction in the levels of dipeptidyl peptidase and sucrase-isomaltase mRNA, markers of Caco-2 cell differentiation. Cytokines interleukin-1beta (IL-1beta), basic fibroblast growth factor, IL-2, epidermal growth factor, and transforming growth factor-beta modulated steady-state levels of Eck and B61 mRNA and regulated Eck activation as assessed by tyrosine phosphorylation. Functionally, stimulation of Eck by B61 resulted in increased proliferation, enhanced barrier function, and enhanced restitution of injured epithelial monolayers. These results suggest that the Eck-B61 interaction, a target of regulatory peptides, plays a role in intestinal epithelial cell development, migration, and barrier function, contributing to homeostasis and preservation of continuity of the epithelial barrier.
Apolipoprotein E: A potent inhibitor of endothelial and tumor cell proliferation (1994)

Recombinant human apolipoprotein E3 (apoE), purified from E. coli, inhibited the proliferation of several cell types, including endothelial cells and tumor cells in a dose- and time-dependent manner. ApoE inhibited both de novo DNA synthesis and proliferation as assessed by an increase in cell number. Maximal inhibition of cell growth by apoE was achieved under conditions where proliferation was dependent on heparin-binding growth factors. Thus, at low serum concentrations (0-2.5%) basic fibroblast growth factor (bFGF) stimulated the proliferation of bovine aortic endothelial (BAE) cells severalfold. The bFGF-dependent proliferation was dramatically inhibited by apoE with an IC50 approximately 50 nM. Under conditions where cell proliferation was mainly serum-dependent, apoE also suppressed growth but required higher concentrations to be effective (IC50 approximately 500 nM). ApoE also inhibited growth of bovine corneal endothelial cells, human melanoma cells, and human breast carcinoma cells. The IC50 values obtained with these cells were generally 3-5 times higher than with BAE cells. Inhibition of cell proliferation by apoE was reversible and dependent on the time of apoE addition to the culture. In addition, apoE inhibited the chemotactic response of endothelial cells that were induced to migrate by a gradient of soluble bFGF. Inhibition of cell proliferation by apoE may be mediated both by competition for growth factor binding to proteoglycans and by an antiadhesive activity of apoE. The present results demonstrate that apoE is a potent inhibitor of proliferation of several cell types and suggest that apoE may be effective in modulating angiogenesis, tumor cell growth, and metastasis.
Familial combined hyperlipidemia and abnormal lipoprotein lipase. (1992)

A previous study reported that heterozygotes for lipoprotein lipase (LPL) deficiency have reduced LPL, the lipoprotein pattern classified as familial combined hyperlipidemia (FCHL), elevated apolipoprotein (apo) B levels, and reduced high density lipoprotein (HDL) levels. These findings suggest that subjects with reduced LPL may form one subset of the FCHL population. The purpose of the present study is to determine whether a subset of patients with FCHL have reduced LPL. Three patient populations with FCHL were studied: 1) subjects with the diagnosis of FCHL (n = 9) established by previous family studies, 2) clinic patients with a tentative diagnosis of FCHL (n = 14), and 3) subjects undergoing angiography who had coronary artery disease (CAD) and a diagnosis of FCHL by family study (n = 33). Two of nine subjects with the established diagnosis of FCHL, five of the 14 FCHL clinic patients, and 13 of the 33 CAD subjects with FCHL had reduced LPL activity in the same range as do individuals who are obligate heterozygotes for LPL deficiency. Subjects with FCHL and reduced LPL had higher plasma triglyceride (p < 0.01) and lower HDL cholesterol (p < 0.025) levels than did the subjects with FCHL and normal LPL levels (327 +/- 201 versus 210 +/- 122 mg/dl [mean +/- SD] and 36 +/- 7 versus 44 +/- 13 mg/dl, respectively). Thus, in all three groups of patients with apparent FCHL, 20 of 56 subjects (36%) had reduced LPL, suggesting that one subset of the FCHL population may be identified by an abnormality in LPL activity that is associated with lipoprotein abnormalities.
The Efficacy of Corneal Cross-Linking Shows a Sudden Decrease with Very High Intensity UV Light and Short Treatment Time (2013)

The ex vivo results of corneal cross-linking performed in porcine corneas show that the Bunsen-Roscoe reciprocity law is only valid for illumination intensities up to 40 to 50 mW/cm(2) and illumination times of more than 2 minutes. Further experiments are necessary to validate these results for in vivo human corneal tissue. Additionally, safety aspects at high intensities must be investigated.
Complete cloning and sequencing of rat gp330/"megalin," a distinctive member of the low density lipoprotein receptor gene family. (1994)

We completed the cDNA cloning and sequencing of gp330, the major kidney glomerular antigen for rat Heymann nephritis. The deduced 4660-aa sequence, expected to constitute a mature protein of M(r) 516,715, consists of a probable N-terminal signal peptide sequence (25 aa), an extracellular region (4400 aa), a single transmembrane domain (22 aa), and a C-terminal cytoplasmic tail (213 aa). The extracellular region contains three types of cysteine-rich repeats characteristic of the low density lipoprotein receptor (LDLR) gene family--36 LDLR ligand-binding repeats forming four clusters of putative ligand-binding domains, 16 growth factor repeats separated by 8 YWTD spacer regions, and 1 C-terminal epidermal growth factor repeat. The cytoplasmic tail contains two copies of the (FX)NPXY motif, which represents a signal for coated pitmediated internalization and an additional similar motif. The overall structure of gp330 is similar to that of the LDLR-related protein (LRP)/alpha 2-macroglobulin receptor and shows even greater similarity to the Caenorhabditis elegans protein, reported as a homologue of LRP. However, gp330 differs from these proteins in (i) the cysteine-rich repeat arrangements found in the extreme extracellular N- and C-terminal regions, (ii) the distribution pattern of cysteine residues in the YWTD spacer regions, (iii) the location of the RX(K/R)R consensus recognition sequence of furin, a precursor processing endoprotease, and (iv) the length and structure of the cytoplasmic tail. We suggest the name megalin (from Greek mega) for gp330, the largest plasma membrane protein identified so far in vertebrates. The cloned cDNA will be useful for studies on the physiological functions of gp330/megalin and for determining its role in Heymann nephritis.
Immune responses to novel Escherichia coli and Salmonella typhimurium vectors that express colonization factor antigen I (CFA/I) of enterotoxigenic E. coli in the absence of the CFA/I positive regulator cfaR (1995)

An asd-stabilized plasmid carrying enterotoxigenic Escherichia coli cfaABCE genes was constructed and called pJGX15C-asd+. Expression of colonization factor antigen I (CFA/I) by this plasmid occurs independently of the cfaABCE positive regulator cfaR in attenuated Salmonella delta aro delta asd strain H683 and nonpathogenic laboratory E. coli asd strain chi 6212. Oral immunization of mice with nonpathogenic E. coli chi 6212 (pJGX15C-asd+) does not elicit significant serum or mucosal responses against CFA/I. In contrast, oral immunization with a single dose of attenuated S. typhimurium H683(pJGX15C-asd+) elicits a 10(5)-fold increase in CFA/I-specific serum immunoglobulin G and significant elevation of CFA/I-specific immunoglobulin A-secreting B cells in the lamina propria, mesenteric lymph nodes, and spleen. Thus, only the Salmonella-CFA/I construct effectively delivered CFA/I to the inductive sites of the gut-associated and systemic lymphoid tissues.
Viral gene therapy for central nervous system diseases (2008)

The idea of using genes as medicines was initially proposed in 1972 by Friedmann and Roblin before it was possible to identify specific genes within genomes, before the discovery of restriction enzymes to cut and paste DNA, and before the development of efficient gene delivery vehicles such as viral vectors [1]. The idea of using genes as medicines to treat diseases was a logical outcome of the identification of complex diseases resulting from mutations in single genes. If complex phenotypes were the result of mutations in a single gene, gene replacement into the right tissue at the right developmental stage should suffice to prevent or even reverse the disease progression. The implementation of this originally simple idea has ushered in a new and exciting era of therapeutic molecular medicine (i.e., gene therapy). Over the past 15 years, hundreds of gene therapy clinical trials have been implemented demonstrating therapeutic results in a growing number of genetic disorders, from relatively simple monogenic inborn errors of metabolism to complex diseases such as cancer.
Square-root, reciprocal, sine/cosine, arctangent cell for signal and image processing (2002)

This paper discusses an efficient interpolation method for nonlinear function generation. Based on this, a 24 bit VLSI cell, capable of computing the (1) square root, (2) reciprocal, (3) sine/cosine, and (4) arctangent functions, is presented for single precision floating-point applications. A 53 bit version, suitable for double precision computations, is also presented. Finally, an extension of the method to the two dimensional nonlinear functions is briefly addressed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An enhanced MITOMAP with a global mtDNA mutational phylogeny (2006)

The MITOMAP (http://www.mitomap.org) data system for the human mitochondrial genome has been greatly enhanced by the addition of a navigable mutational mitochondrial DNA (mtDNA) phylogenetic tree of approximately 3000 mtDNA coding region sequences plus expanded pathogenic mutation tables and a nuclear-mtDNA pseudogene (NUMT) data base. The phylogeny reconstructs the entire mutational history of the human mtDNA, thus defining the mtDNA haplogroups and differentiating ancient from recent mtDNA mutations. Pathogenic mutations are classified by both genotype and phenotype, and the NUMT sequences permits detection of spurious inclusion of pseudogene variants during mutation analysis. These additions position MITOMAP for the implementation of our automated mtDNA sequence analysis system, Mitomaster.
Chemoselective ligation techniques: Modern applications of time‐honored chemistry (2010)

Chemoselective ligation techniques enable the selective modification of proteins and other biomolecules in dilute aqueous solution. Importantly, these reactions occur at or near physiological pH and are compatible with the complex array of functional groups commonly found in biological macromolecules including proteins, nucleotides, and carbohydrates, allowing conjugation reactions to be carried out on unprotected substrates. Recently, a growing number of reactions with established utility in synthetic organic chemistry have been shown to have surprising utility in the context of biological molecules in aqueous media. In this review we highlight several promising reactions that may have widespread applicability in the generation of new materials based on biological macromolecules.
Selective depletion of factor XI or factor XII with antisense oligonucleotides attenuates catheter thrombosis in rabbits (2014)

Central venous catheter thrombosis can cause venous obstruction and pulmonary embolism. To determine the extent to which catheter thrombosis is triggered by the contact or extrinsic pathway of coagulation, we used antisense oligonucleotides (ASOs) to selectively knock down factor (f)XII, fXI, or high-molecular-weight kininogen (HK), key components of the contact pathway, or fVII, which is essential for the extrinsic pathway. Knockdown of contact pathway components prolonged the activated partial thromboplastin time and decreased target protein activity levels by over 90%, whereas fVII knockdown prolonged the prothrombin time and reduced fVII activity to a similar extent. Using a rabbit model of catheter thrombosis, catheters implanted in the jugular vein were assessed daily until they occluded, up to a maximum of 35 days. Compared with control, fXII and fXI ASO treatment prolonged the time to catheter occlusion by 2.2- and 2.3-fold, respectively. In contrast, both HK and fVII knockdown did not significantly prolong the time to occlusion, and dual treatment with fVII- and fXI-directed ASOs produced a time to occlusion similar to that with the fXI ASO alone. These findings suggest that catheter thrombosis is triggered via the contact pathway and identify fXII and fXI as potential targets to attenuate this complication.
Synthesis and biological activity of several amino analogues of thymidine. (1978)

3',5'-Diamino-3',5'-dideoxythymidine (7) was synthesized via a nine-step synthesis from thymidine in good overall yield. 3'-Amino-3'-deoxythymidine (8) and 5'-amino-5'-deoxythymidine (12) were prepared with a minor modification of the procedure reported by Horwitz and co-workers. Although the 5'-amino analogue 12 had potent antiviral activity relative to the 3'-amino analogue 8, the latter is a potent inhibitor of the replication of both murine sarcoma 180 cells (ED50 = 5 micrometer) and of murine L1210 cells (ED50 = 1 micrometer) in vitro. Most unexpectedly, however, was the finding of complete lack of either antiviral or antineoplastic activity by the 3',5'-diamino analogue 7 which appears to have acquired the undesirable qualities of both the 3'-amino and 5'-amino analogues of thymidine.
Neural source-filter-based waveform model for statistical parametric speech synthesis (2018)

Neural waveform models such as the WaveNet are used in many recent text-to-speech systems, but the original WaveNet is quite slow in waveform generation because of its autoregressive (AR) structure. Although faster non-AR models were recently reported, they may be prohibitively complicated due to the use of a distilling training method and the blend of other disparate training criteria. This study proposes a non-AR neural source-filter waveform model that can be directly trained using spectrum-based training criteria and the stochastic gradient descent method. Given the input acoustic features, the proposed model first uses a source module to generate a sine-based excitation signal and then uses a filter module to transform the excitation signal into the output speech waveform. Our experiments demonstrated that the proposed model generated waveforms at least 100 times faster than the AR WaveNet and the quality of its synthetic speech is close to that of speech generated by the AR WaveNet. Ablation test results showed that both the sine-wave excitation signal and the spectrum-based training criteria were essential to the performance of the proposed model.
The native virulence plasmid combination affects the segregational stability of a theta-replicating shuttle vector in Bacillus anthracis var. New Hampshire (1999)

Journal Article The native virulence plasmid combination affects the segregational stability of a theta‐replicating shuttle vector in Bacillus anthracis var. New Hampshire Get access J. E. Bowen, J. E. Bowen Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wilts, UK Search for other works by this author on: Oxford Academic Google Scholar C. P. Quinn C. P. Quinn Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wilts, UK Search for other works by this author on: Oxford Academic Google Scholar Journal of Applied Microbiology, Volume 87, Issue 2, 1 August 1999, Pages 270–278, https://doi.org/10.1046/j.1365-2672.1999.00885.x Published: 01 August 1999 Article history Revision received: 15 May 1999 Accepted: 29 May 1999 Published: 01 August 1999