gebhart/patrepeval huggingface dataset:
Comparison of Human Papillomavirus Messenger RNA and DNA Detection: A Cross-sectional Study of 4,136 Women &gt;30 Years of Age with a 2-Year Follow-up of High-Grade Squamous Intraepithelial Lesion (2005)

The purpose of this study was to compare the detection of human papillomavirus (HPV) DNA with detection of mRNA. The study included 4,136 women >30 years of age. E6/E7 mRNA expression from the carcinogenic HPV types 16, 18, 31, 33, and 45 was detected by the PreTect HPV-Proofer assay, whereas the presence of HPV DNA was detected by Gp5+/6+ consensus PCR followed by type-specific PCR. A total of 4.0% had an abnormal cytologic diagnosis, 3.0% were positive by PreTect HPV-Proofer, 4.4% by type-specific PCR, and 10.4% by consensus PCR. For detection of HPV in high-grade squamous intraepithelial lesion (HSIL), no significant difference was observed between PreTect HPV-Proofer and consensus PCR. For women with a cytologic normal, atypical squamous cell of uncertain significance, and low-grade SIL diagnosis, the detection rate of HPV was significantly higher by Gp5+/6+ consensus PCR (P < 0.005) than by PreTect HPV-Proofer. Histology confirmed 14 of 23 cytologic HSIL as cervical intraepithelial neoplasia grade >2. Of these women, PreTect HPV-Proofer and type-specific PCR detected 12, whereas consensus PCR detected 13. In conclusion, for HSIL, detection of E6/E7 transcripts from HPV types 16, 18, 31, 33, and 45 are present to the same degree as DNA detected by consensus PCR. Equally important, only a small proportion of the HPV DNA-positive women with a normal, atypical squamous cell of uncertain significance or low-grade SIL diagnosis had a detectable mRNA expression. HPV E6/E7 mRNA detection by PreTect HPV-Proofer represents a new promising test as an adjunct to cytology.
Characterization of a Baculovirus-Encoded RNA 5′-Triphosphatase (1998)

Autographa californica nuclear polyhedrosis virus (AcNPV) encodes a 168-amino-acid polypeptide that contains the signature motif of the superfamily of protein phosphatases that act via a covalent cysteinyl phosphate intermediate. The sequence of the AcNPV phosphatase is similar to that of the RNA triphosphatase domain of the metazoan cellular mRNA capping enzyme. Here, we show that the purified recombinant AcNPV protein is an RNA 5'-triphosphatase that hydrolyzes the gamma-phosphate of triphosphate-terminated poly(A); it also hydrolyzes ATP to ADP and GTP to GDP. The phosphatase sediments as two discrete components in a glycerol gradient: a 9.5S oligomer and 2.5S putative monomer. The 2.5S form of the enzyme releases 32Pi from 1 microM gamma-32P-labeled triphosphate-terminated poly(A) with a turnover number of 52 min-1 and converts ATP to ADP with Vmax of 8 min-1 and Km of 25 microM ATP. The 9.5S oligomeric form of the enzyme displays an initial pre-steady-state burst of ADP and Pi formation, which is proportional to and stoichiometric with the enzyme, followed by a slower steady-state rate of product formation (approximately 1/10 of the steady-state rate of the 2.5S enzyme). We surmise that the oligomeric enzyme is subject to a rate-limiting step other than reaction chemistry and that this step is either distinct from or slower than the rate-limiting step for the 2.5S enzyme. Replacing the presumptive active site nucleophile Cys-119 by alanine abrogates RNA triphosphatase and ATPase activity. Our findings raise the possibility that baculoviruses encode enzymes that cap the 5' ends of viral transcripts synthesized at late times postinfection by a virus-encoded RNA polymerase.
Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis. (1996)

In patients with rheumatoid arthritis the synovial membrane of the affected joint is infiltrated with lymphoid cells which may be arranged in structures resembling germinal centers. We have directly isolated such infiltrates to determine whether B-cell clones within them are selected and expanded in a process analogous to that which normally takes place in the germinal centers in secondary lymphoid organs. The data suggest that an antigen-driven process leads to the accumulation of B cells in the synovial membrane. The finding of identical sequences in consecutive sections suggests that under conditions of chronic stimulation, memory B cells may enter a stage of differentiation in which they proliferate without further accumulation of somatic mutations. Further we see intraclonal diversity which underlines the germinal center-like character of these infiltrates and demonstrates that a microenvironment is built up in this nonlymphoid tissue which supports antigen-dependent differentiation of B cells. This is the first demonstration, to our knowledge, of a germinal center-like reaction outside lymphoid tissue.
Asymmetric Ni(II)/Cr(II)-Mediated Coupling Reaction:  Catalytic Process (2002)

[reaction: see text] The stable, crystalline Cr(III)/sulfonamide complex 1a is shown to be an effective catalyst for the Ni/Cr-mediated coupling reaction. A possible mechanism is suggested for the process. 1a is also effective for other Cr-mediated coupling reactions. With this catalyst, a concise and efficient synthesis of the C14-C26 segment of halichondrins has been developed.
Pritumumab binding to glioma cells induces ADCC and inhibits tumor growth. (2017)

e14004 Background: Pritumumab is a natural human IgG1 kappa antibody originally isolated from a regional draining lymph node of a patient with cervical carcinoma. This antibody binds ectodomain vimentin on the surface of tumor cells and has demonstrated some benefit to glioblastoma patients in limited clinical trials. We wanted to determine if pritumumab inhibits glioma growth in vivo and if binding to glioma cells induces cell-mediated immunity. Methods: Pritumumab was used in flow cytometry experiments with several glioma cell lines and patient-derived neurosphere lines. Antibody-dependent cell-mediated cytotoxicity (ADCC) reporter assay was used with glioma target cells. Xenograft studies were performed in mice with and without intact B- and NK- cells. Results: We performed flow cytometry using pritumumab antibody and demonstrate binding of pritumumab to the surface of glioma cells and patient-derived glioma initiating cells. We observed significant induction of ADCC by pritumumab binding to glioma cells. Xenograft studies demonstrated pritumumab was effective in preventing tumor growth in nude mice but not in SCID mice. Intact cell-mediated immunity was necessary for pritumumab’s anti-tumor effect. Analysis of a blood brain barrier model showed significant binding of pritumumab in brain tumor areas and minimal distribution in normal brain tissues suggesting the antibody can cross the blood brain barrier. Conclusions: Our data demonstratepritumumab binds glioma cells in vitro and can induce ADCC. In addition, pritumumab can limit the growth of xenograft glioma tumors in vivo only in the presence of intact cell-mediated immunity. Together these data suggest pritumumab is suitable for development as an anti-tumor therapeutic.
Dendritic Cells are preferentially targeted among hematolymphocytes by Modified Vaccinia Virus Ankara and play a key role in the induction of virus-specific T cell responses in vivo (2008)

Modified Vaccinia Ankara (MVA) is a highly attenuated strain of vaccinia virus (VV) that has lost approximately 15% of the VV genome, along with the ability to replicate in most mammalian cells. It has demonstrated impressive safety and immunogenicity profile in both preclinical and clinical studies, and is being actively explored as a promising vaccine vector for a number of infectious diseases and malignancies. However, little is known about how MVA interacts with the host immune system constituents, especially dendritic cells (DCs), to induce strong immune responses despite its inability to replicate in vivo. Using in vitro and in vivo murine models, we systematically investigated the susceptibility of murine DCs to MVA infection, and the immunological consequences of the infection. Our data demonstrate that MVA preferentially infects professional antigen presenting cells, especially DCs, among all the subsets of hematolymphoid cells. In contrast to the reported blockage of DC maturation and function upon VV infection, DCs infected by MVA undergo phenotypic maturation and produce innate cytokine IFN-α within 18 h of infection. Substantial apoptosis of MVA-infected DCs occurs after 12 h following infection and the apoptotic DCs are readily phagocytosed by uninfected DCs. Using MHC class I – deficient mice, we showed that both direct and cross-presentation of viral Ags are likely to be involved in generating viral-specific CD8+ T cell responses. Finally, DC depletion abrogated the T cell activation in vivo. We present the first in vivo evidence that among hematolymphoid cells, DCs are the most susceptible targets for MVA infection, and DC-mediated Ag presentation is required for the induction of MVA-specific immune responses. These results provide important information concerning the mechanisms by which strong immune responses are elicited to MVA-encoded antigens and may inform efforts to further improve the immunogenicity of this already promising vaccine vector.
Inhibition of ceramide-induced apoptosis by Bcl-2. (1995)

Ceramide, a long chain sphingolipid that is generated intracellularly upon hydrolysis of membrane-associated sphingomyelin, has recently been implicated as a second messenger-like molecule that is produced distal to ligation of the tumour necrosis factor receptor type 1 (TNFR1), as well as the related Fas (CD95/Apo-1) molecule. It is well established that ligation of TNFR1 or Fas leads to apoptosis in most cases. Furthermore, it has also recently been demonstrated that exposure to cell-permeable synthetic ceramides can result in apoptosis in many cases. These and other observations have led to the hypothesis that accumulation of intracellular ceramide may be a common element of several pathways that result in apoptosis. Here we show that exposure to synthetic ceramides triggers apoptosis in the human T lymphoblastoid cell lines, CEM and Jurkat, and that overexpression of the apoptosis-repressor protein, Bcl-2, renders these cells resistant to the apoptosis-inducing effects of ceramide, as well as to several other stimuli. Since exposure to ceramides can result in either cell proliferation, differentiation, cycle arrest, or death, the level of Bcl-2 expression in a cell may be an important factor in determining the outcome of signals that result in intracellular generation of this sphingolipid.
Cloning and Characterization of Human Prostate Coactivator ARA54, a Novel Protein That Associates with the Androgen Receptor (1999)

Androgen receptor (AR) is a member of the steroid receptor superfamily that may require coactivators for proper or maximal transactivation. Using a yeast two-hybrid screening followed by mammalian cell analyses, we identified a novel ligand-dependent AR-associated protein, ARA54, which consists of 474 amino acids with a molecular mass of 54 kDa. We demonstrated that ARA54 might function as a preferential coactivator for AR-mediated transactivation in human prostate cancer DU145 cells. Interestingly, our data also showed that ARA54 could significantly enhance the transcriptional activity of LNCaP mutant AR (ARt877a) but not wild type AR or another mutant AR (ARe708k) in the presence of 10 nM 17beta-estradiol or 1 microM hydroxyflutamide. These results imply that both ARA54 and the positions of the AR mutation (877 versus 708) might contribute to the specificity of AR-mediated transactivation. Our findings further demonstrated that the C-terminal domain of ARA54 can serve as a dominant negative inhibitor and exogenous full-length ARA54 can reverse this squelching effect on AR transcriptional activity. Co-expression of ARA54 with other AR coactivators, such as ARA70 or SRC-1, showed additive stimulation of AR-mediated transactivation, which indicates that these cofactors may function individually as AR coactivators to induce AR target gene expression. Through our findings, we have identified and characterized a novel AR coactivator, ARA54, which may play an important role in the AR signaling pathway in human prostate.
Fluidic microsystems based on printed circuit board technology (2001)

In this paper, fluidic microsystems based on an alternative fabricating technology are described. This technology mainly utilizes the manufacturing principles of printed circuit boards (PCBs). Minimal lateral structure dimensions of approximately 100 µm und vertical dimensions of some 10 µm are feasible. By introducing thin polymeric foils (6-13 µm in thickness) into a stack of PCBs, movable parts forming active or passive valves, pumps or sensors can be produced. The first results concerning several fluidic components based on PCB technology are presented.
Gene Targeting by Homologous Recombination as a Biotechnological Tool for Rice Functional Genomics (2007)

Abstract The modification of an endogenous gene into a designed sequence by homologous recombination, termed gene targeting (GT), has broad implications for basic and applied research. Rice (Oryza sativa), with a sequenced genome of 389 Mb, is one of the most important crops and a model plant for cereals, and the single-copy gene Waxy on chromosome 6 has been modified with a frequency of 1% per surviving callus by GT using a strong positive-negative selection. Because the strategy is independent of gene-specific selection or screening, it is in principle applicable to any gene. However, a gene in the multigene family or a gene carrying repetitive sequences may preclude efficient homologous recombination-promoted GT due to the occurrence of ectopic recombination. Here, we describe an improved GT procedure whereby we obtained nine independent transformed calli having the alcohol dehydrogenase2 (Adh2) gene modified with a frequency of approximately 2% per surviving callus and subsequently isolated eight fertile transgenic plants without the concomitant occurrence of undesirable ectopic events, even though the rice genome carries four Adh genes, including a newly characterized Adh3 gene, and a copy of highly repetitive retroelements is present adjacent to the Adh2 gene. The results indicate that GT using a strong positive-negative selection can be widely applicable to functional genomics in rice and presumably in other higher plants.
No evidence of intelligence improvement after working memory training: A randomized, placebo-controlled study. (2012)

Numerous recent studies seem to provide evidence for the general intellectual benefits of working memory training. In reviews of the training literature, Shipstead, Redick, and Engle (2010, 2012) argued that the field should treat recent results with a critical eye. Many published working memory training studies suffer from design limitations (no-contact control groups, single measures of cognitive constructs), mixed results (transfer of training gains to some tasks but not others, inconsistent transfer to the same tasks across studies), and lack of theoretical grounding (identifying the mechanisms responsible for observed transfer). The current study compared young adults who received 20 sessions of practice on an adaptive dual n-back program (working memory training group) or an adaptive visual search program (active placebo-control group) with a no-contact control group that received no practice. In addition, all subjects completed pretest, midtest, and posttest sessions comprising multiple measures of fluid intelligence, multitasking, working memory capacity, crystallized intelligence, and perceptual speed. Despite improvements on both the dual n-back and visual search tasks with practice, and despite a high level of statistical power, there was no positive transfer to any of the cognitive ability tests. We discuss these results in the context of previous working memory training research and address issues for future working memory training studies.
Why Market-Valuation-Indifferent Indexing Works (2005)

Using market values for indexing gives more portfolio weight to the stocks with positive price errors and less portfolio weight to the stocks with negative price errors. Market-valuation-indifferent indexing—such as equal weighting or weighting by number of employees, number of customers, or sales—relies on averaging over hundreds of stocks to give equal weight to the two groups.
Palladium-Catalyzed Aromatic Aminations with in situ Generated Aminostannanes (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPalladium-Catalyzed Aromatic Aminations with in situ Generated AminostannanesAnil S. Guram and Stephen L. BuchwaldCite this: J. Am. Chem. Soc. 1994, 116, 17, 7901–7902Publication Date (Print):August 1, 1994Publication History Published online1 May 2002Published inissue 1 August 1994https://pubs.acs.org/doi/10.1021/ja00096a059https://doi.org/10.1021/ja00096a059research-articleACS PublicationsRequest reuse permissionsArticle Views9842Altmetric-Citations636LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Scaling single cell transcriptomics through split pool barcoding (2017)

Constructing an atlas of cell types in complex organisms will require a collective effort to characterize billions of individual cells. Single cell RNA sequencing (scRNA-seq) has emerged as the main tool for characterizing cellular diversity, but current methods use custom microfluidics or microwells to compartmentalize single cells, limiting scalability and widespread adoption. Here we present Split Pool Ligation-based Transcriptome sequencing (SPLiT-seq), a scRNA-seq method that labels the cellular origin of RNA through combinatorial indexing. SPLiT-seq is compatible with fixed cells, scales exponentially, uses only basic laboratory equipment, and costs one cent per cell. We used this approach to analyze 109,069 single cell transcriptomes from an entire postnatal day 5 mouse brain, providing the first global snapshot at this stage of development. We identified 13 main populations comprising different types of neurons, glia, immune cells, endothelia, as well as types in the blood-brain-barrier. Moreover, we resolve substructure within these clusters corresponding to cells at different stages of development. As sequencing capacity increases, SPLiT-seq will enable profiling of billions of cells in a single experiment.
Final report of a phase II evaluation of paclitaxel in patients with advanced squamous cell carcinoma of the head and neck (1998)

These results indicate that paclitaxel is an active agent for the treatment of squamous cell carcinoma of the head and neck. Studies evaluating alternative infusion schedules and combination regimens currently are underway.
Expression of a naturally occurring constitutively active variant of the epidermal growth factor receptor in mouse fibroblasts increases motility (2003)

Tumor cell motility is one of the rate-limiting steps of invasion, which defines progression toward a more malignant phenotype. Elevated expression of epidermal growth factor receptor (EGFR) in many cancers is associated with progression of superficial to invasive forms of the disease. The naturally occuring type III mutant epidermal growth factor receptor (EGFRvIII) is a tumor-specific, ligand-independent, constitutively active variant of the epidermal growth factor receptor. EGFRvIII is expressed frequently by a number of human solid tumours including those of the lung, breast, prostate, brain and ovary. Our study was designed to investigate the effect of EGFRvIII expression on cell motility and compare it to that of ligand-activated EGFR using transfected fibroblasts. We show here using time-lapse video recording that expression of EGFRvIII greatly enhances the motility of fibroblasts independently of ligand stimulation. In addition, expression of EGFRvIII caused a marked increase in the number of cellular protrusions (lamellipodia) and a reduction in the number of stress fibers and focal adhesions. The EGFR tyrosine kinase inhibitor, AG1478, and the MEK inhibitor, U0126, blocked these cellular effects of EGFRvIII. Two cell lines expressing different levels of EGFR were used for comparison. The low-expressing cell line responded to EGF treatment by increasing motility in a manner very similar to the motility induced by EGFRvIII. In contrast, the high-expressing cell line responded to EGF by detachment from the extracellular matrix and decreased motility. Cellular detachment was correlated to a high phosphorylation of PLC-gamma, whereas increased motility was correlated to a high level of ERK phosphorylation. Overall these results indicate that tumor-associated EGFR mutations might be critical for tumor cell motility, invasion and thus progression of disease.
Time Controlled Protein Release from Layer‐by‐Layer Assembled Multilayer Functionalized Agarose Hydrogels (2010)

2 was produced incorrectly, resulting in a loss of fidelity in the microscopy images.
Phenylethanolamine N‐methyltransferase (PNMT) gene and early‐onset Alzheimer disease (2001)

The activity of human phenylethanolamine N-methyltransferase (PNMT) is reduced in the neurons of those cells in many subcortical areas of the brain that are known to undergo neurodegeneration in Alzheimer disease (AD). Others have reported that PNMT is decreased in brains of persons with AD and that the decrease in enzymatic activity is due to a reduced amount of the enzyme protein. We have previously described two polymorphisms, G-353A and G-148A, in the promoter region of the gene coding for PNMT. These markers were tested for their association with the occurrence of sporadic AD. Genotyping of 131 necropsy confirmed AD cases, and 947 adult nondemented controls were completed. We observed a significant association between both of the PNMT gene polymorphisms and early-onset AD (EOAD) (P < or = 0.007), but not in late-onset AD (LOAD). These data suggest that genetic variation in the promoter of the PNMT gene is associated with increased susceptibility to the sporadic form of EOAD.