gebhart/patrepeval huggingface dataset:
Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance (2000)

Targeting the tyrosine kinase activity of Bcr-Abl with STI571 is an attractive therapeutic strategy in chronic myelogenous leukemia (CML). A few CML cell lines and primary progenitors are, however, resistant to this compound. We investigated the mechanism of this resistance in clones of the murine BaF/3 cells transfected with BCR-ABL and in 4 human cell lines from which sensitive (s) and resistant (r) clones were generated by various methods. Although the resistant cells were able to survive in the presence of STI571, their proliferation was approximately 30% lower than that of their sensitive counterparts in the absence of the compound. The concentration of STI571 needed for a 50% reduction in viable cells after a 3-day exposure was on average 10 times higher in the resistant (2-3 micromol/L) than in the sensitive (0.2-0.25 micromol/L) clones. The mechanism of resistance to STI571 varied among the cell lines. Thus, in Baf/BCR-ABL-r, LAMA84-r, and AR230-r, there was up-regulation of the Bcr-Abl protein associated with amplification of the BCR-ABL gene. In K562-r, there was no Bcr-Abl overexpression, but the IC(50) for the inhibition of Bcr-Abl autophosphorylation was increased in the resistant clones. Sequencing of the Abl kinase domain revealed no mutations. The multidrug resistance P-glycoprotein (Pgp) was overexpressed in LAMA84-r, indicating that at least 2 mechanisms of resistance operate in this cell line. KCL22-r showed neither Bcr-Abl up-regulation nor a higher threshold for tyrosine kinase inhibition by STI571. We conclude that BCR-ABL-positive cells can evade the inhibitory effect of STI571 by different mechanisms, such as Bcr-Abl overexpression, reduced intake mediated by Pgp, and, possibly, acquisition of compensatory mutations in genes other than BCR-ABL.
Studies on the inhibition of ellagic acid-activated Hageman factor (factor XII) and Hageman factor fragments (1981)

Hageman factor (HF, factor XII) that has been exposed to Sephadex- ellagic acid gels is a single-chain species (HFea) with amidolytic properties for the synthetic substrate H-D-phenylalanyl-L-pipecolyl-L- arginine p-nitroanilide. Earlier we reported that amidolysis was suppressed by incubation of HFea with specific antiserum. The present study provides additional evidence that the amidolytic properties of preparations of HFea are ascribable to this substance through an examination of a number of protease inhibitors. HFea's amidolytic properties were inhibited by alpha 2-plasmin inhibitor, antithrombin III in the presence of heparin, and Cl esterase inhibitor (Cl-INH). Additionally, it was inhibited by popcorn inhibitor, leupeptin, hexadimethrine bromide, protamine sulfate, dansyl-arginine N-(3-ethyl- 1,5-pentanediyl) amide (DAPA), diisopropylphosphofluoridate (DFP), aprotinin, and at excessively high concentrations, soybean and lima bean trypsin inhibitors. The spectrum of action of agents that did or did not inhibit HFea supports the view that amidolysis by preparations of HFea is attributable to this enzyme. In general, the enzymatically active carboxy-terminal fragment of HF (HFf) was inhibited by the same agents that inhibited HFea, but aprotinin, protamine sulfate and hexadimethrine bromide were more effective against HFf than HFea, while the reverse was true of lima bean trypsin inhibitor.
Alpha 2-macroglobulin-proteinase complexes, plasminogen activator inhibitor type-1-plasminogen activator complexes, and receptor-associated protein bind to a region of the alpha 2-macroglobulin receptor containing a cluster of eight complement-type repeats (1993)

A region containing sites for ligand binding was localized in the 4525-amino acid residue alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein (alpha 2MR/LRP) by ligand- and immunoblotting of proteinase and CNBr digests of the purified human placental protein. 125I-Labeled rat alpha 1-macroglobulin light chain, urokinase-plasminogen activator inhibitor type-1 complex, and alpha 2MR-associated protein all bound to a 75-kDa CNBr-generated fragment (68 kDa after deglycosylation). In addition to the three ligands, the fragment bound a novel monoclonal antibody reacting in the region defined by amino acid residues 1165-1246 as determined by binding to recombinant fragments of alpha 2MR/LRP. The positions of methionine residues in alpha 2MR/LRP suggested that the ligand-binding CNBr fragment contained three disulfide-linked peptides comprising the residues 776-1399. This origin was confirmed by partial amino acid sequencing of the electroblotted fragment and polypeptides generated by reduction of the fragment. The identified region represents 13.6% of the molecular mass (nonglycosylated) of alpha 2MR/LRP and contains one of three large clusters of complement-type repeats.
HCV RNA in patients with chronic hepatitis C treated with interferon‐α (1993)

In order to assess the efficacy of interferon-alpha on hepatitis C viral RNA in patients with chronic hepatitis C, we analyzed the levels of HCV RNA in sera and liver tissues of 16 patients pre- and posttreatment using a semiquantitative polymerase chain reaction method. Fifteen of 16 patients were positive for anti-HCV antibodies by four-antigen recombinant immunoblot assay (4-RIBA). Only two patients demonstrated normalization of ALT in response to interferon; three patients showed a partial response. Only one patient from the partial responder group displayed a significant reduction of HCV RNA level posttreatment. In the nonresponder group, several patients, although their ALTs remained elevated, demonstrated significant decreases in HCV RNA levels in either serum or liver in response to interferon. Our data suggest that interferon treatment of chronic hepatitis C may not be effective in eradicating HCV infection and a reduction in ALT is infrequently associated with a decrease in HCV RNA level in either serum or liver. Cessation of treatment is frequently associated with the recrudescence of HCV replication and disease.
Intravitreal Injection of AAV2 Transduces Macaque Inner Retina (2011)

The results in the macaque suggest that intravitreal injection of AAV2 would produce high levels of gene expression at the human fovea, important in retinal gene therapy, but not in the central retina beyond the fovea.
Molecular Basis of Triple Negative Breast Cancer and Implications for Therapy (2011)

Triple negative breast cancer is an aggressive form of breast cancer with limited treatment options and is without proven targeted therapy. Understanding the molecular basis of triple negative breast cancer is crucial for effective new drug development. Recent genomewide gene expression and DNA sequencing studies indicate that this cancer type is composed of a molecularly heterogeneous group of diseases that carry multiple somatic mutations and genomic structural changes. These findings have implications for therapeutic target identification and the design of future clinical trials for this aggressive group of breast cancer.
Temperature shifts in regulation of lipids accumulated byLipomyces starkeyi (1993)

Abstract The effect of temperature on the accumulating triglycerides of Lipomyces starkeyi was studied in 10‐L fermentation experiments. The temperature during the growth, lipid accumulation and postaccumulation phases was altered. The cellular lipid content, the glucose conversion efficiency and the specific lipid production rate were highest when the growth phase temperature was 28°C, instead of 16–18°C. The temperature of the accumulation phase had an influence on the lipid quality at the end of the accumulation. Oleic acid content increased from 52 to over 60% when the accumulation phase temperature was decreased from 28 to 15°C and, concomitantly, palmitic acid decreased from 33 to 26%. The degree of fatty acid unsaturation was the highest (0.75 Δmol −1 ) when the accumulation phase temperature was the lowest (15°C) and vice versa . The temperature shift after the lipid accumulation phase affected neither the composition nor the amount of the accumulated lipids. In conclusion, the temperature profile for the highest lipid yield with the most desired composition should be: (i) a growth phase temperature that gives the maximum growth rate and (ii) an accumulation phase temperature that produces the desired ratio of palmitic to oleic acid.
Nanomaterials Based Electrochemical Sensing Applications for Safety and Security (2012)

Abstract Nanomaterials based sensing systems provide a new class of rapid and low cost detection alternatives with interest in the field of safety and security applications. In this review we report the recent trends in the use of various nanomaterials such as nanoparticles, carbon nanotubes, nanowires and graphene to detect different safety and security related analytes (i.e. microorganisms, toxins, pesticides and explosives). Nanomaterials are used either as modifiers of the electrochemical transducers or as labels with the objective to enhance the electrochemical signal, improve the stability and in general the performance of the detection systems including their cost‐efficiency. Most of the developed systems are shown to bring excellent improvements while being used in the laboratory. Their application in real sample and during in‐field monitoring still needs a long way while issues such as the reproducibility, stability, mass production capability of the designed devices etc. shouldn’t still yet be resolved.
Moving Object Detection in Spatial Domain using Background Removal Techniques - State-of-Art (2010)

Identifying moving objects is a critical task for many computer vision applications; it provides a classification of the pixels into either foreground or background. A common approach used to achieve such classification is background removal. Even though there exist numerous of background removal algorithms in the literature, most of them follow a simple flow diagram, passing through four major steps, which are pre-processing, background modelling, foreground de- tection and data validation. In this paper, we survey many existing schemes in the literature of background removal, sur- veying the common pre-processing algorithms used in different situations, presenting different background models, and the most commonly used ways to update such models and how they can be initialized. We also survey how to measure the performance of any moving object detection algorithm, whether the ground truth data is available or not, presenting per- formance metrics commonly used in both cases.
Canadian Initiatives for Locally Advanced Breast Cancer Research and Treatment: Inaugural Meeting of the Canadian Consortium for LABC (2011)

The inaugural Canadian Consortium for LABC (locally advanced breast cancer) conference was held at Langdon Hall, Cambridge, Ontario, April 11–12, 2010. The meeting focused on current and future directions in labc treatment and research, the specific benefits of labc as a model for clinical and translational research, strategies for increased national and international collaboration, and ongoing clinical trials. Exciting Canadian initiatives in labc research are underway, focusing on identifying molecular signatures that will allow for the development of new tailored therapies. The challenge of identifying patient subgroups for accrual is being addressed through strategies to foster and improve national collaboration. This meeting report includes highlights from each presentation at the conference.
Manufacturing test of SoCs (2003)

In this paper the solution the industry is driving towards for manufacturing test of SoCs is described. The quality of test for every core that is integrated on the chip is very important to the overall quality of the SoC. In this paper a method for evaluating the quality needs of an embedded core relative to the embedded environment is presented. Due to the partitioning of the test data and the increased stress in quality for individual designs the test application time is increasing. This paper presents the problems associated with test application time with SoCs.
A nuclear magnetic resonance study of transmission of electronic effects. Ethylbenzenes, dihydrocinnamic acids, and cis- and trans-cinnamic acids (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA nuclear magnetic resonance study of transmission of electronic effects. Ethylbenzenes, dihydrocinnamic acids, and cis- and trans-cinnamic acidsThomas A. Wittstruck and Edward N. TrachtenbergCite this: J. Am. Chem. Soc. 1967, 89, 15, 3803–3809Publication Date (Print):July 1, 1967Publication History Published online1 May 2002Published inissue 1 July 1967https://pubs.acs.org/doi/10.1021/ja00991a021https://doi.org/10.1021/ja00991a021research-articleACS PublicationsRequest reuse permissionsArticle Views222Altmetric-Citations25LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Simple, high‐efficiency synthesis of fatty acid methyl esters from soapstock (2000)

Abstract We report a simple method that efficiently esterifies the fatty acids in soapstock, an inexpensive, lipid‐rich by‐product of edible oil production. The process involves (i) alkaline hydrolysis of all lipid‐linked fatty acid ester bonds and (ii) acid‐catalyzed esterification of the resulting fatty acid sodium salts. Step (i) completely saponified all glycerides and phosphoglycerides in the soapstock. Following water removal, the resulting free fatty acid sodium salts were rapidly and quantitatively converted to fatty acid methyl esters (FAME) by incubation with methanol and sulfuric acid at 35°C and ambient pressure. Minimum molar reactant ratios for full esterification were fatty acids/methanol/sulfuric acid of 1∶30∶5. The esterification reaction was substantially complete within 10 min and was not inhibited by residual water contents up to ca. 10% in the saponified soapstock. The product FAME contained &gt;99% fatty acid esters, 0% triglycerides, &lt;0.05% diglycerides, &lt;0.1% monoglycerides, and &lt;0.8% free fatty acids. Free fatty acid levels were further reduced by washing with dilute sodium hydroxide. Free and total glycerol were &lt;0.01 and &lt;0.015%, respectively. The water content was &lt;0.04%. These values meet the current specifications for biodiesel, a renewable substitute for petroleum‐derived diesel fuel. The identities and proportions of fatty acid esters in the FAME reflected the fatty acid content of soybean lipids. Solids formed during the reaction contained 69.1% ash and 0.8% protein. Their sodium content indicated that sodium sulfate was the prime inorganic component. Carbohydrate was the predominant organic constituent of the solid.
Transient expression from cab-m1 and rbcS-m3 promoter sequences is different in mesophyll and bundle sheath cells in maize leaves. (1992)

Cell-specific and light-regulated expression of the beta-glucuronidase (GUS) reporter gene from maize cab-m1 and rbcS-m3 promoter sequences was studied in maize leaf segments by using an in situ transient expression microprojectile bombardment assay. The cab-m1 gene is known to be strongly photoregulated and to be expressed almost exclusively in mesophyll cells (MC) but not in bundle sheath cells (BSC). Expression of GUS from a 1026-base-pair 5' promoter fragment of cab-m1 is very low in dark-grown leaves; GUS expression is increased about 10-fold upon illumination of dark-grown leaves. In illuminated leaves, the ratio of GUS expression in MC vs. BSC is about 10:1. The cab-m1 region between 868 and 1026 base pairs 5' to the translation start confers strong MC-preferred expression on the remainder of the chimeric gene in illuminated leaves, but a region between -39 and -359 from the translation start is required for photoregulated expression. Transcripts of rbcS-m3 are found in BSC but not in MC and are about double in BSC of greening dark-grown seedlings. In contrast to the behavior of the cab-m1-GUS construct, GUS expression driven by 2.1 kilobase pairs of the rbcS-m3 5' region was about twice as high in MC as in BSC of unilluminated dark-grown maize leaves. The number of BSC, but not MC, expressing GUS nearly doubled upon greening of bombarded etiolated leaves. These data suggest that the 5' region of rbcS-m3 used here could be responsible for most of the light-dependent increase in rbcS-m3 transcripts observed in BSC of greening leaves and that transcriptional or posttranscriptional mechanisms are responsible for the lack of rbcS-m3 transcripts in MC.
A New Approach to the Construction of Surfaces from Contour Data (1994)

Abstract This paper presents a new approach to the construction of a surface from a stack of contour slices. Unlike most existing methods, this new approach handles ambiguous conditions consistently without employing an algorithm to establish a correspondence between vertices on one contour and those on the next. It is easy to implement and fast to compute, requiring only basic geometric properties, namely closedness and simplicity, to be available with contour data. The advantages of this new approach have also been demonstrated with solutions to a few classical problems from the literature and some practical problems in medical imaging. It can also be applied to geographical surveying and keyframe animations.
Recent Advances in Catalytic Intramolecular CH Aminations (2005)

CN bond formation by nitrene-induced CH amination is an elegant class of reaction (see scheme). The Highlight describes how such intramolecular processes are catalytic with transition metals and display enantioselectivity to provide a powerful synthetic tool ideally suited to the synthesis of natural products.
Polar/apolar chemical inducers of differentiation of transformed cells: strategies to improve therapeutic potential. (1989)

N,N'-Hexamethylenebisacetamide (HMBA) induces transformed cells to differentiate, accompanied by suppression of oncogenicity. Clinical trials have shown that HMBA can cause positive therapeutic responses in some cancer patients, but clinical efficacy may be limited, in part, by dose-related toxicity. Potential improvements in efficacy may be accomplished by changes in the chemical structure of inducing agents and by increasing the sensitivity of tumor cells to inducers of differentiation. We have previously described an approach to improving tumor cell responsiveness to inducing agents. Transformed cell lines that have acquired low levels of resistance to vincristine display a markedly increased sensitivity to HMBA. We now report on a series of hybrid polar/apolar compounds--some of which are as active as HMBA and several of which are significantly more active than HMBA in vitro--whose chemical structures make it likely that they have different pharmacokinetics. Vincristine-resistant murine erythroleukemia cells also are shown to have marked increased sensitivity to these hybrid polar/apolar compounds. Thus these findings suggest potentially useful strategies for the application of polar/apolar inducers of differentiation to the treatment of cancers. These studies also provide approaches to further understanding of the biological process of terminal differentiation.
The Role of Exercise Testing in the Modern Management of Pulmonary Arterial Hypertension (2014)

A culture of exercise testing is firmly embedded in the management of pulmonary arterial hypertension (PAH) but its clinical relevance and utility have recently been under some debate. The six minute walk test (6MWT) has been used as a primary outcome measure to enable the licensing of many of the medications used for this condition. Recent reviews have questioned the validity of this test as a surrogate of clinical outcomes. At the same time, other questions are emerging where exercise testing may be the solution. With the rise in understanding of genetic markers of idiopathic PAH (IPAH), the screening of an otherwise healthy population for incipient pulmonary hypertension (PH) will be required. The proliferation in treatment choices and identification of populations with PH where PAH treatment is not indicated, such as left heart and lung disease, requires more definitive differentiation from patients with PAH. There is a continuing question about the existence and clinical relevance of exercise induced PAH as a cause of unexplained dyspnoea and fatigue and as a latent phase of resting PH. This review presents a summary and critical analysis of the current role of exercise testing in PAH and speculates on future trends.
Broadband supercontinuum generation with excellent spectral stability from a highly-nonlinear fibre using an amplified noiselike-pulse train (2005)

We demonstrate high-power, broadband supercontinuum (SC) generation by using noiselike pulses amplified by a conventional EDFA. The flat SC spectrum with excellent spectral stability of +/-0.03 dB is achieved from 1050 nm to 1600 nm. (2 pages)
Generation of immunity to the HER-2/neu oncogenic protein in patients with breast and ovarian cancer using a peptide-based vaccine. (1999)

HER-2/neu is a "self" tumor antigen that is overexpressed in 15-30% of human adenocarcinomas. Vaccine strategies directed against HER-2/neu and other self tumor antigens require development of methods to overcome immune tolerance to self-proteins. In rats, rat neu peptide vaccines have been shown to be an effective way of circumventing tolerance to rat neu protein and generating rat neu-specific immunity. The present report validates that a similar peptide-based vaccine formulation is effective for inducing T-cell immunity to HER-2/neu protein in humans with breast and ovarian cancer. The vaccine formulation included groups of peptides derived from the HER-2/neu extracellular domain (ECD) or intracellular domain (ICD) mixed with granulocyte macrophage colony stimulating factor as an adjuvant. These peptides were 15-18 amino acids in length and designed to elicit a CD4 T helper-specific immune response. Patients underwent intradermal immunization once a month for a total of two to six immunizations. To date, all of the patients immunized with HER-2/neu peptides developed HER-2/neu peptide-specific T-cell responses. The majority of patients (six of eight) also developed HER-2/neu protein-specific responses. Responses to HER-2/neu protein occurred with epitope spreading. Immune T cells elicited by vaccination were shown to migrate outside the peripheral circulation by virtue of generating delayed type hypersensitivity responses distant from the vaccine site, which indicated the potential ability to traffic to the site of tumor. The use of peptide-based vaccines may be a simple, yet effective, vaccine strategy for immunizing humans to oncogenic self-proteins.