gebhart/patrepeval huggingface dataset:
Modulation of Splicing by Single-Stranded Silencing RNAs (2015)

Single-stranded silencing RNAs (ss-siRNAs) are chemically modified single-stranded oligonucleotides that can function through the cellular RNA interference (RNAi) machinery to modulate gene expression. Because their invention is recent, few studies have appeared describing their use and the potential of ss-siRNAs as a platform for controlling gene expression remains largely unknown. Using oligonucleotides to modulate splicing is an important area for therapeutic development and we tested the hypothesis that ss-siRNAs targeting splice sites might also be capable of directing increased production of therapeutically promising protein isoforms. Here we observe that ss-siRNAs alter splicing of dystrophin. Altered splicing requires a seed sequence complementarity to the target and expression of the RNAi factor argonaute 2. These results demonstrate that ss-siRNAs can be used to modulate splicing, providing another option for therapeutic development programs that aim to increase production of key protein isoforms. Splicing is a classical nuclear process and our data showing that it can be modulated through the action of RNA and RNAi factors offers further evidence that RNAi can take place in mammalian cell nuclei.
Expression of alpha 2-macroglobulin receptor/low density lipoprotein receptor-related protein and scavenger receptor in human atherosclerotic lesions. (1994)

Macrophage- and smooth muscle cell (SMC)-derived foam cells are typical constituents of human atherosclerotic lesions. At least three receptor systems have been characterized that could be involved in the development of foam cells: alpha 2-macroglobulin receptor/LDL receptor-related protein (alpha 2 MR/LRP), scavenger receptor, and LDL receptor. We studied the expression of these receptors in human atherosclerotic lesions with in situ hybridization and immunocytochemistry. An abundant expression of alpha 2MR/LRP mRNA and protein was found in SMC and macrophages in both early and advanced lesions in human aortas. alpha 2MR/LRP was also present in SMC in normal aortas. Scavenger receptor mRNA and protein were expressed in lesion macrophages but no expression was found in lesion SMC. LDL receptor was absent from the lesion area but was expressed in some aortas in medial SMC located near the adventitial border. The results demonstrate that (a) alpha 2MR/LRP is, so far, the only lipoprotein receptor expressed in lesions SMC in vivo; (b) scavenger receptors are expressed only in lesion macrophages; and (c) both receptors may play important roles in the development of human atherosclerotic lesions.
Cellular interactions in the generation of cytolytic T lymphocyte responses: role of Ia-positive splenic adherent cells in presentation in H-2 antigen. (1980)

Splenic adherent cells are required for generation of both primary and, at limiting antigen dose, secondary allogeneic responses of cytolytic T lymphocytes to intact stimulator cells. Secondary responses to purified allogeneic plasma membranes or purified H-2Kk antigens in liposomes are also dependent upon splenic adherent cells. Generation of these responses requires the presence of an Ia-positive. Thy 1,2-negative, radiation-resistant cell in the splenic adherent cell population that is adherent to glass, plastic, and nylon wool. Stimulation of cytolytic T lymphocyte precursors with purified H-2Kk alloantigen bound to Ia+ splenic adherent cells is 10-20 times more efficient than stimulation with antigen added directly to culture. Furthermore, a marked decrease in the response of cytolytic T lymphocytes to liposomes was observed when antiserum against Iad specific for the Ia of the responder cells was added to culture. These results demonstrate that, for purified proteins of the major histocompatibility complex, antigen presentation by Ia+ splenic adherent cells plays a role in the generation of a cytolytic T lymphocyte response.
Transport of <scp>l</scp>‐arginine and nitric oxide formation in human platelets (2003)

The results of the present study show that human platelets take up l-arginine by two transport systems which are compatible with the systems y+ and y+L. These Na+independent transporters have been distinguished by treating platelets with N-ethylmaleimide that blocks selectively system y+. System y+, that accounts for 30-40% of the total transport, is characterized by low affinity for l-arginine, is unaffected by l-leucine, is sensitive to changes of membrane potential and to trans-stimulation. The other component of l-arginine transport identified with the system y+L (approximately 60-70% of the total flux) shows high affinity for l-arginine, is insensitive to N-ethylmaleimide treatment, unaffected by changes in membrane potential, sensitive to trans-stimulation and inhibited by l-leucine in the presence of Na+. Moreover a strict correlation between l-arginine transport and nitric oxide (NO) production in whole cells was found. N-ethylmaleimide and l-leucine decreased NO production as well as cGMP elevation, and the effect on NO and cGMP were closely related. It is likely that the l-arginine transport systems y+ and y+L are both involved in supplying substrate for NO production and regulation in human platelets.
Variations on the Fresnel Zone Plate (1966)

The effects of contrast in the Fresnel zone plate on the amplitude in the focal point due to a normally incident plane wave are obtained by direct evaluation of the Fresnel–Kirchhoff diffraction integral. The change in focal-point amplitude due to smoothing the ordinary, discontinuous, “square-wave” transmission function into a continuous, “sine-wave” function is also calculated. Finally, an expression is derived for the amplitude in the point image due to a plane wave impinging on the zone plate at a small angle of incidence.
Phase I Study of Anti–Epidermal Growth Factor Receptor Antibody Cetuximab in Combination With Radiation Therapy in Patients With Advanced Head and Neck Cancer (2001)

Cetuximab can be safely administered with RT. The recommended dose for phase II/III studies is a loading dose of 400 to 500 mg/m(2) and a maintenance weekly dose of 250 mg/m(2).
Fabrication and Use of Nanometer-Sized Electrodes in Electrochemistry (1990)

Electrodes with electrochemical dimensions as small as 10 angstroms have been fabricated and used for electrochemical studies. These nanometer-scale electrodes have enabled the measurement of electron-transfer rate constants, k(het), that are two orders of magnitude faster than k(het) values accessible with any other electrochemical method.
Relationship between gut microbiota and development of T cell associated disease (2014)

The interplay between the immune response and the gut microbiota is complex. Although it is well-established that the gut microbiota is essential for the proper development of the immune system, recent evidence indicates that the cells of the immune system also influence the composition of the gut microbiota. This interaction can have important consequences for the development of inflammatory diseases, including autoimmune diseases and allergy, and the specific mechanisms by which the gut commensals drive the development of different types of immune responses are beginning to be understood. Furthermore, sex hormones are now thought to play a novel role in this complex relationship, and collaborate with both the gut microbiota and immune system to influence the development of autoimmune disease. In this review, we will focus on recent studies that have transformed our understanding of the importance of the gut microbiota in inflammatory responses.
Improved production and purification of recombinant proteins from mammalian expression systems (2017)

The biopharmaceutical industry is becoming increasingly reliant on recombinant proteins as therapeutic agents. The work presented here details the development of rapid mammalian expression systems and novel capture methods for use in early recombinant protein development. A key aim was to investigate expression of recombinant proteins via cost effective production methods and to compare the resultant products at small scales of manufacture. A model single chain variable fragment Fc conjugate (scFv-Fc) targeted against a clinically relevant glycoprotein, the carcinoembryonic antigen (CEA), was expressed and characterised using both transient and stable-based expression of transgenic DNA. Transient gene expression in suspension HEK293 cells produced a maximum scFv-Fc level of 72μg/mL, which was used for initial protein characterisation. A stable pool of transfected CHO cells was also generated using a ubiquitous chromatin opening element (UCOE)-based vector achieving increased protein expression and culture periods when combined with a fed-batch regimen. Characterisation of the resulting proteins showed that stability and effector function was maintained across transient and stable production methods at all scales, indicating that preliminary data generated from transient expression in HEK293F cells could be generalised to predict that of protein stably expressed in CHO cell populations. A significant bottleneck in harvesting and purifying proteins from cell containing feed streams is the requirement for solid-liquid separation prior to capture. Therefore, a technique was proposed for direct capture of recombinant protein from unclarified feed streams that can integrate directly into the bioreactor harvest line. The process was demonstrated using immobilised metal affinity chromatography (IMAC) capture of recombinant CEA with a polyhistidine (His6) tag from a bioreactor culture. This provides a basis for direct primary capture of recombinant proteins from unclarified mammalian cell feed streams that could be generalized to other capture methods and proteins.
Hepatocyte Growth Factor/Scatter Factor Promotes Adhesion of Lymphoma Cells to Extracellular Matrix Molecules Via α4β1 and α5β1 Integrins (1997)

Hepatocyte growth factor (HGF)/scatter factor (SF) is the ligand for a tyrosine kinase cell surface receptor encoded by the MET protooncogene (c-MET). HGF/SF can induce proliferation and motility in epithelial cells and promotes invasion of carcinoma cells and NIH3T3 fibroblasts transfected with both HGF/SF and c-MET genes. Our results show that HGF/ SF and c-MET also play a role in adhesion and invasion of human lymphoma cells. c-MET mRNA is expressed in hemopoietic cells, such as hemopoietic progenitor cells (CD34+ cells) in bone marrow (BM) and mobilized peripheral blood, immature B cells in cord blood and BM, and germinal center B-centroblasts. In normal peripheral blood B cells, which are c-MET-, c-MET expression was induced by PMA, ConA, HGF/ SF, and Epstein-Barr virus (EBV) infection. Using immunohistochemistry, we detected c-MET on the cell surface of large activated centroblasts in lymph nodes from patients with B-non-Hodgkin's lymphoma and Hodgkin's disease. In the latter group, c-MET expression correlated well with the presence of EBV. Because HGF/SF and c-MET promote metastasis of carcinoma cells, we studied the effects of c-MET stimulation by HGF/SF of B-lymphoma cells on properties relevant for metastasis, ie, adhesion, migration, and invasion. HGF/SF stimulated adhesion of the c-MET+ B-cell lines to the extracellular matrix molecules fibronectin (FN) and collagen (CN) in a dose dependent manner. However, adhesion to laminin was not affected by HGF/SF. Adhesion to FN was mediated by beta 1-integrins alpha 4 beta 1 (VLA4) and alpha 5 beta 1 (VLA5) since blocking antibodies against beta 1- (CD29), alpha 4-(CD49d), or alpha 5- (CD49e) integrin subunits, completely reversed the effect of HGF/SF. Furthermore, HGF/SF induced adhesion was abrogated by addition of genistein, which blocks protein tyrosine kinases, including c-MET. Addition of HGF/SF resulted in a sixfold increase in migration of c-MET B-lymphoma cells through Matrigel, compared to medium alone. In rat fibroblast cultures, HGF/SF doubled the number of c-MET+ B-lymphoma cells that invaded the fibroblast monolayer. In these adhesion, migration and invasion assays HGF/SF had no effect on c-MET- cell lines. In conclusion, c-MET is expressed or can be induced on immature, activated, and certain malignant B cells. HGF/SF increased adhesion of c-MET+ B-lymphoma cells to FN and CN, mediated via beta 1-integrins alpha 4 beta 1 and alpha 5 beta 1, and furthermore promoted migration and invasion.
Modular barcode beads for microfluidic single cell genomics (2021)

Barcode beads allow efficient nucleic acid tagging in single cell genomics. Current barcode designs, however, are fabricated with a particular application in mind. Repurposing to novel targets, or altering to add additional targets as information is obtained is possible but the result is suboptimal. Here, we describe a modular framework that simplifies generation of multifunctional beads and allows their easy extension to new targets.
Carbon-13 NMR study of curing in furfuryl alcohol resins (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbon-13 NMR study of curing in furfuryl alcohol resinsI Ssuer Chuang, Gary E. Maciel, and George E. MyersCite this: Macromolecules 1984, 17, 5, 1087–1090Publication Date (Print):May 1, 1984Publication History Published online1 May 2002Published inissue 1 May 1984https://pubs.acs.org/doi/10.1021/ma00135a019https://doi.org/10.1021/ma00135a019research-articleACS PublicationsRequest reuse permissionsArticle Views610Altmetric-Citations96LEARN 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
Differential Representations for Mesh Processing (2006)

Abstract Surface representation and processing is one of the key topics in computer graphics and geometric modeling, since it greatly affects the range of possible applications. In this paper we will present recent advances in geometry processing that are related to the Laplacian processing framework and differential representations. This framework is based on linear operators defined on polygonal meshes, and furnishes a variety of processing applications, such as shape approximation and compact representation, mesh editing, watermarking and morphing. The core of the framework is the definition of differential coordinates and new bases for efficient mesh geometry representation, based on the mesh Laplacian operator.
Consumption of C4b-binding protein (C4BP) during<i>in vivo</i>activation of the classical complement pathway (1999)

C4BP has a central role in regulating the classical complement (C') pathway, but it is still uncertain whether or not it is consumed during in vivo complement activation. Attempts to demonstrate changes in C4BP plasma levels in systemic lupus erythematosus and essential mixed cryoglobulinaemia have failed, probably due to up-regulation of this protein during the inflammatory reaction. We have studied one patient with severe post-transfusion complement-mediated anaphylaxis (CMA), and 67 patients with hereditary C1 inhibitor deficiency (hereditary angioedema (HAE)). The first of these two conditions is characterized by the absence of systemic inflammatory reaction and the second by acute and chronic activation of the C' classical pathway. C4BP, C4BP-C4b complex, and soluble terminal C' complex (sC5b-9) were measured in the patients' plasmas by ELISA techniques and C3a and C4a by radioimmunoassays. In CMA, 15 min after the transfusion, there was a massive C' activation, with increases in C4a, C3a, sC5b-9, C4BP-C4b complexes and decreases in C4, C3 and C4BP. All parameters reverted to preinfusion values within 24 h. Depletion of C4 was correlated with that of C4BP. In patients with HAE, the median value of C4BP (83% range 54-165) was significantly lower (P < 0.0001) than in normal controls (99% range 70-159), with no difference between patients in remission or during acute attacks. C4BP-C4b complexes could not be detected in HAE patients. The results of this study indicate that C4BP is consumed in vivo during acute, and possibly during chronic activation of the C' classical pathway, and that this protein, after interaction with C4b, not longer circulates in plasma.
The role of melanoma tumor‐derived nitric oxide in the tumor inflammatory microenvironment: Its impact on the chemokine expression profile, including suppression of CXCL10 (2011)

Melanoma appears to be heterogeneous in terms of its molecular biology, etiology and epidemiology. We previously reported that the expression of inducible nitric-oxide synthase (iNOS) in melanoma tumor cells is strongly correlated with poor patient survival. Therefore, we hypothesized that nitric oxide (NO) produced by iNOS promotes the melanoma inflammatory tumor microenvironment associated with poor outcome. To understand the role of NO and iNOS in the melanoma inflammatory tumor microenvironment, polymerase chain reaction arrays of inflammatory and autoimmunity genes were performed on a series of stage III melanoma lymph node metastasis samples to compare the gene expression profiles of iNOS-expressing and nonexpressing tumor samples. The results indicate that expression of CXC chemokine ligand 10 (CXCL10) was inversely correlated with iNOS expression, and the high CXCL10-expressing cases had more favorable prognoses than the low CXCL10-expressing cases. Functional studies revealed that treating iNOS-negative/CXCL10-positive melanoma cell lines with a NO donor suppressed the expression of CXCL10. Furthermore, scavenging NO from iNOS-expressing cell lines significantly affected the chemokine expression profile. Culture supernatants from NO scavenger-treated melanoma cells promoted the migration of plasmacytoid dendritic cells, which was diminished when the cells were treated with a CXCL10-neutralizing antibody. CXCL10 has been reported to be an antitumorigenic chemokine. Our study suggests that the production of NO by iNOS inhibits the expression of CXCL10 in melanoma cells and leads to a protumorigenic tumor microenvironment. Inhibiting NO induces an antitumorigenic environment, and thus, iNOS should be considered to be an important therapeutic target in melanoma.
Counting of apoptotic cells: a methodological study in invasive breast cancer (1996)

Aims-To arrive at a reproducible sampling technique for counting apoptotic cells in tissue sections of invasive breast cancer that can serve as a protocol for further clinical studies.Methods-In 4 mum thick haematoxylin and eosin stained tissue sections of 12 breast cancers, apoptotic cells, recognised by strict morphological criteria, were counted in consecutive fields of vision at x1000 magnification in a marked area in the most poorly differentiated region of tumour. These counts were regarded as the gold standard. Subsequently, in a systematic sampling experiment, the number of fields that had to be counted to derive an acceptable coefficient of variation (CV) was determined. To compare counts at different magnifications, all fields of vision were also counted at x630 and x400. The intra- and inter-observer reproducibility was tested by repeated measurements at these magnifications in 10 systematically selected fields of vision.Results-Apoptosis seemed to be a rare event, affecting, on average, about 1% of tumour cells. Noticeable clustering of apoptotic cells was observed. The systematic sampling experiment showed that at x1000 magnification, the CV was improved by counting up to 20 fields. When comparing x400 and x630 magnifications with the x1000 magnification, the correlation coefficients were 0.88 and 0.87, respectively. However, the lower magnifications yielded lower counts. With regard to reproducibility, the intra-observer correlation coefficient was 0.91 at x630 and 0.76 at x400. The inter-observer correlation coefficient was 0.77 at x630 and 0.68 at x400.Conclusions-Apoptotic cells can be counted readily in haematoxylin and eosin stained tissue sections. However, a systematic sampling protocol must be followed and cells should be counted at a relatively high magnification to obtain acceptable reproducibility. The suggested protocol will permit further correlative and prognostic studies and the monitoring of the effects of treatment.
Cytokinin signaling regulates cambial development in poplar (2008)

Although a substantial proportion of plant biomass originates from the activity of vascular cambium, the molecular basis of radial plant growth is still largely unknown. To address whether cytokinins are required for cambial activity, we studied cytokinin signaling across the cambial zones of 2 tree species, poplar (Populus trichocarpa) and birch (Betula pendula). We observed an expression peak for genes encoding cytokinin receptors in the dividing cambial cells. We reduced cytokinin levels endogenously by engineering transgenic poplar trees (P. tremula x tremuloides) to express a cytokinin catabolic gene, Arabidopsis CYTOKININ OXIDASE 2, under the promoter of a birch CYTOKININ RECEPTOR 1 gene. Transgenic trees showed reduced concentration of a biologically active cytokinin, correlating with impaired cytokinin responsiveness. In these trees, both apical and radial growth was compromised. However, radial growth was more affected, as illustrated by a thinner stem diameter than in WT at same height. To dissect radial from apical growth inhibition, we performed a reciprocal grafting experiment. WT scion outgrew the diameter of transgenic stock, implicating cytokinin activity as a direct determinant of radial growth. The reduced radial growth correlated with a reduced number of cambial cell layers. Moreover, expression of a cytokinin primary response gene was dramatically reduced in the thin-stemmed transgenic trees. Thus, a reduced level of cytokinin signaling is the primary basis for the impaired cambial growth observed. Together, our results show that cytokinins are major hormonal regulators required for cambial development.
Determining object orientation from a single image using multiple information sources (2018)

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