gebhart/patrepeval huggingface dataset:
Reusable Solid-Phase Supports for Oligonucleotide Synthesis Using Hydroquinone-O,O'-diacetic Acid (“Q-Linker”) (1999)

Abstract Reusable solid-phase supports for large scale oligonucleotide synthesis have been prepared by converting amino derivatized supports into hydroxyl supports. Rapid nucleo side attachment, via a Q-linker arm, was automatically performed on the DNA synthesizer using HBTU and DMAP as the coupling reagents. All steps were suitable for automation and ∼ 1.5 h was required to prepare the supports for reuse. Up to twelve consecutive syntheses of a 20-mer phosphorothioate were performed on a synthesis column.
Potato Extract (Potein) Suppresses Food Intake in Rats through Inhibition of Luminal Trypsin Activity and Direct Stimulation of Cholecystokinin Secretion from Enteroendocrine Cells (2011)

Dietary proteins and trypsin inhibitors are known to stimulate the secretion of the satiety hormone cholecystokinin (CCK). A potato extract (Potein) contains 60% carbohydrate and 20% protein including trypsin inhibitory proteins. In this study, we examined whether Potein suppresses food intake in rats and whether it directly stimulates CCK secretion in enteroendocrine cells. In fasted rats, food consumption was measured up to 6 h after the oral administration of Potein or soybean trypsin inhibitor (SBTI). CCK-releasing activities of Potein and SBTI were examined in the murine CCK-producing cell line STC-1. Potein inhibited the trypsin activity in vitro with a potency 20-fold lower than that of SBTI. Oral administration of Potein dose-dependently suppressed food intake for 1-6 h. Potein, but not the SBTI, dose-dependently induced CCK secretion in STC-1 cells. These results suggest that Potein suppresses food intake through the CCK secretion induced by direct stimulation on enteroendocrine cells and through inhibition of luminal trypsin.
Novel candidate colorectal cancer biomarkers identified by methylation microarray-based scanning (2011)

DNA hypermethylation is a common epigenetic abnormality in colorectal cancers (CRCs) and a promising class of CRC screening biomarkers. We conducted a genome-wide search for novel neoplasia-specific hypermethylation events in the colon. We applied methylation microarray analysis to identify loci hypermethylated in 17 primary CRCs relative to eight non-neoplastic colonic mucosae (NCs) from neoplasia-free subjects. These CRC-associated hypermethylation events were then individually evaluated for their ability to discriminate neoplastic from non-neoplastic cases, based on real-time quantitative methylation-specific PCR (qMSP) assays in 113 colonic tissues: 51 CRCs, nine adenomas, 19 NCs from CRC patients (CRC-NCs), and 34 NCs from neoplasia-free subjects (control NCs). A strict microarray data filtering identified 169 candidate CRC-associated hypermethylation events. Fourteen of these 169 loci were evaluated using qMSP assays. Ten of these 14 methylation events significantly distinguished CRCs from age-matched control NCs (P<0.05 by receiver operator characteristic curve analysis); methylation of visual system homeobox 2 (VSX2) achieved the highest discriminative accuracy (83.3% sensitivity and 92.3% specificity, P<1×10(-6)), followed by BEN domain containing 4 (BEND4), neuronal pentraxin I (NPTX1), ALX homeobox 3 (ALX3), miR-34b, glucagon-like peptide 1 receptor (GLP1R), BTG4, homer homolog 2 (HOMER2), zinc finger protein 583 (ZNF583), and gap junction protein, gamma 1 (GJC1). Adenomas were significantly discriminated from control NCs by hypermethylation of VSX2, BEND4, NPTX1, miR-34b, GLP1R, and HOMER2 (P<0.05). CRC-NCs were significantly distinguished from control NCs by methylation of ALX3 (P<1×10(-4)). In conclusion, systematic methylome-wide analysis has identified ten novel methylation events in neoplastic and non-neoplastic colonic mucosae from CRC patients. These potential biomarkers significantly discriminate CRC patients from controls. Thus, they merit further evaluation in stool- and circulating DNA-based CRC detection studies.
Sequence-Specific Inhibition of Small RNA Function (2004)

Hundreds of microRNAs (miRNAs) and endogenous small interfering RNAs (siRNAs) have been identified from both plants and animals, yet little is known about their biochemical modes of action or biological functions. Here we report that 2'-O-methyl oligonucleotides can act as irreversible, stoichiometric inhibitors of small RNA function. We show that a 2'-O-methyl oligonucleotide complementary to an siRNA can block mRNA cleavage in Drosophila embryo lysates and HeLa cell S100 extracts and in cultured human HeLa cells. In Caenorhabditis elegans, injection of the 2'-O-methyl oligonucleotide complementary to the miRNA let-7 can induce a let-7 loss-of-function phenocopy. Using an immobilized 2'-O-methyl oligonucleotide, we show that the C. elegans Argonaute proteins ALG-1 and ALG-2, which were previously implicated in let-7 function through genetic studies, are constituents of a let-7-containing protein-RNA complex. Thus, we demonstrate that 2'-O-methyl RNA oligonucleotides can provide an efficient and straightforward way to block small RNA function in vivo and furthermore can be used to identify small RNA-associated proteins that mediate RNA silencing pathways.
Rediscovering alemtuzumab: current and emerging therapeutic roles (2009)

The humanized anti-CD52 monoclonal antibody alemtuzumab belongs to the family of Campath-1 antibodies, which were initially developed for their ability to prevent graft-versus-host disease (GVHD) and graft rejection in stem cell transplantation. Alemtuzumab is indicated for the treatment of chronic lymphocytic leukaemia (CLL) and has demonstrated considerable activity in relapsed/refractory disease and in previously untreated disease. It has been shown to induce minimal residual disease-negative responses as a single agent or as part of consolidation therapy in a meaningful proportion of patients with CLL and has shown promising activity in patients with high-risk cytogenetic markers. Alemtuzumab may also have significant activity in T-cell malignancies, such as mycosis fungoides and T-cell prolymphocytic leukaemia. Recent studies also have evaluated alemtuzumab as part of a conditioning regimen to prevent GVHD in stem cell transplantation. This article reviews our current understanding of alemtuzumab and discusses its emerging role in the treatment of CLL and other haematological malignancies.
Finding Oxygen Reservoir by Using Extremely Small Test Cell Structure for Resistive Random Access Memory with Replaceable Bottom Electrode (2015)

Abstract Although the presence of an oxygen reservoir (OR) is assumed in many models that explain resistive switching of resistive random access memory (ReRAM) with electrode/metal oxide (MO)/electrode structures, the location of OR is not clear. We have previously reported a method, which involved the use of an AFM cantilever, for preparing an extremely small ReRAM cell that has a removable bottom electrode (BE). In this study, we used this cell structure to specify the location of OR. Because an anode is often assumed to work as OR, we investigated the effect of changing anodes without changing the MO layer and the cathode on the occurrence of reset. It was found that the reset occurred independently of the catalytic ability and Gibbs free energy (ΔG) of the anode. Our proposed structure enabled to determine that the reset was caused by repairing oxygen vacancies of which a filament consists due to the migration of oxygen ions from the surrounding area when high ΔG anode metal is used, whereas by oxidizing the anode due to the migration of oxygen ions from the MO layer when low ΔG anode metal is used, suggesting the location of OR depends on ΔG of the anode.
TTC7A mutations disrupt intestinal epithelial apicobasal polarity (2013)

Multiple intestinal atresia (MIA) is a rare cause of bowel obstruction that is sometimes associated with a combined immunodeficiency (CID), leading to increased susceptibility to infections. The factors underlying this rare disease are poorly understood. We characterized the immunological and intestinal features of 6 unrelated MIA-CID patients. All patients displayed a profound, generalized lymphocytopenia, with few lymphocytes present in the lymph nodes. The thymus was hypoplastic and exhibited an abnormal distribution of epithelial cells. Patients also had profound disruption of the epithelial barrier along the entire gastrointestinal tract. Using linkage analysis and whole-exome sequencing, we identified 10 mutations in tetratricopeptide repeat domain–7A (TTC7A), all of which potentially abrogate TTC7A expression. Intestinal organoid cultures from patient biopsies displayed an inversion of apicobasal polarity of the epithelial cells that was normalized by pharmacological inhibition of Rho kinase. Our data indicate that TTC7A deficiency results in increased Rho kinase activity, which disrupts polarity, growth, and differentiation of intestinal epithelial cells, and which impairs immune cell homeostasis, thereby promoting MIA-CID development.
Elimination of Tumor Cells Using Folate Receptor Targeting by Antibody‐Conjugated, Gold‐Coated Magnetite Nanoparticles in a Murine Breast Cancer Model (2012)

Background . The chemotherapeutic treatment of cancer suffers from poor specificity for targeting the tumor cells and often results in adverse effects such as systemic toxicity, damage to nontarget tissues, and development of drug‐resistant tumors in patients. Increasingly, drug nanocarriers have been explored as a way of lessening or overcoming these problems. In this study, antibody‐conjugated Au‐coated magnetite nanoparticles, in conjunction with inductive heating produced by exposure to an oscillating magnetic field (OMF), were evaluated for their effects on the viability of tumor cells in a murine model of breast cancer. Treatment effects were evaluated by light microscopy and SEM. Results . 4T1 mammary epithelial carcinoma cells overexpressing the folate receptor were targeted with an anti‐folate receptor primary antibody, followed by labeling with secondary antibody‐conjugated Au‐coated magnetite nanoparticles. In the absence of OMF exposure, nanoparticle labeling had no effect on 4T1 cell viability. However, following OMF treatment, many of the labeled 4T1 cells showed extensive membrane damage by SEM analysis, and dramatically reduced viability as assessed using a live/dead staining assay. Conclusions . These results demonstrate that Au‐coated magnetite targeted to tumor cells through binding to an overexpressed surface receptor, in the presence of an OMF, can lead to tumor cell death.
Functional Recruitment of Human Complement Inhibitor C4b-Binding Protein to Outer Membrane Protein Rck of Salmonella (2011)

Resistance to complement mediated killing, or serum resistance, is a common trait of pathogenic bacteria. Rck is a 17 kDa outer membrane protein encoded on the virulence plasmid of Salmonella enterica serovars Typhimurium and Enteritidis. When expressed in either E. coli or S. enterica Typhimurium, Rck confers LPS-independent serum resistance as well as the ability to bind to and invade mammalian cells. Having recently shown that Rck binds the inhibitor of the alternative pathway of complement, factor H (fH), we hypothesized that Rck can also bind the inhibitor of the classical and lectin pathways, C4b-binding protein (C4BP). Using flow cytometry and direct binding assays, we demonstrate that E. coli expressing Rck binds C4BP from heat-inactivated serum and by using the purified protein. No binding was detected in the absence of Rck expression. C4BP bound to Rck is functional, as we observed factor I-mediated cleavage of C4b in cofactor assays. In competition assays, binding of radiolabeled C4BP to Rck was reduced by increasing concentrations of unlabeled protein. No effect was observed by increasing heparin or salt concentrations, suggesting mainly non-ionic interactions. Reduced binding of C4BP mutants lacking complement control protein domains (CCPs) 7 or 8 was observed compared to wt C4BP, suggesting that these CCPs are involved in Rck binding. While these findings are restricted to Rck expression in E. coli, these data suggest that C4BP binding may be an additional mechanism of Rck-mediated complement resistance.
PROTECTING THE PUMP: Controlling Myocardial Inflammatory Responses (2005)

Because of the anatomy, function, and nonregenerative nature of the myocardium, inflammation in this tissue is not well tolerated. Nevertheless, various diseases of the heart are characterized by inflammatory responses involving the effector mechanisms of innate and adaptive (lymphocyte-dependent) immunity. The innate immune response to ischemia-reperfusion injury is, by far, the most common cause of myocardial inflammation. Innate responses may have beneficial influences that preserve myocardial function in the short term but may be maladaptive in chronic states. Adaptive responses in the myocardium occur with infection or loss of tolerance, and lead to myocarditis. Given the narrow margin for benefit of cardiac inflammation, special regulatory mechanisms likely raise the threshold, compared to other tissues, for the induction and persistence of adaptive immune responses. These mechanisms include strong central and peripheral T cell tolerance to heart antigens and induction of anti-inflammatory feedback mechanisms involving cytokines such as interferon-gamma.
Phase I Safety, Pharmacokinetic, and Pharmacodynamic Trial of ZD1839, a Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Five Selected Solid Tumor Types (2002)

ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.
Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. (1982)

A simple technique for the simultaneous measurement of relative levels of a specific mRNA in numerous small samples of animal cells or tissue is described. The technique involves denaturation of cytoplasmic preparations, followed by dotting of up to 96 samples onto a single sheet of nitrocellulose, hybridization with a 32P-labeled cDNA plasmid, autoradiography, and scanning. By analyzing cytoplasmic preparations instead of purified RNA, manipulations of multiple samples prior to analysis is minimized. Experiments with a clonal line of rat pituitary tumor (GH3) cells showed that this technique can be employed to follow the induction by Ca2+ of prolactin mRNA sequences, employing cytoplasm prepared from as little as 2.5 x 10(4) cells. The specificity of the technique for prolactin mRNA was shown by employing GC cells, a GH3 cell variant lacking detectable prolactin mRNA sequences. Experiments with cultured rat hemipituitaries showed that the prolactin mRNA present in cytoplasm corresponding to as little as 1/100 of a pituitary could be readily detected. This technique is quite simple, requires very small amounts of cells or tissue, and permits the simultaneous analysis of multiple samples. Hence, it should be quite useful for studies with various experimental systems of the regulation of specific mRNA levels.
Intramolecular Schmidt reaction of alkyl azides (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntramolecular Schmidt reaction of alkyl azidesJeffrey Aube and Gregory L. MilliganCite this: J. Am. Chem. Soc. 1991, 113, 23, 8965–8966Publication Date (Print):November 1, 1991Publication History Published online1 May 2002Published inissue 1 November 1991https://pubs.acs.org/doi/10.1021/ja00023a065https://doi.org/10.1021/ja00023a065research-articleACS PublicationsRequest reuse permissionsArticle Views4541Altmetric-Citations200LEARN 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 (1)»Supporting Information Supporting Information Get e-Alerts
Molecular Mechanisms RegulatinG Th1 Immune Responses (2003)

The T helper lymphocyte is responsible for orchestrating the appropriate immune response to a wide variety of pathogens. The recognition of the polarized T helper cell subsets Th1 and Th2 has led to an understanding of the role of these cells in coordinating a variety of immune responses, both in responses to pathogens and in autoimmune and allergic disease. Here, we discuss the mechanisms that control lineage commitment to the Th1 phenotype. What has recently emerged is a rich understanding of the cytokines, receptors, signal transduction pathways, and transcription factors involved in Th1 differentiation. Although the picture is still incomplete, the basic pathways leading to Th1 differentiation can now be understood in in vitro and a number of infection and disease models.
Improving Biocatalyst Performance by Integrating Statistical Methods into Protein Engineering (2010)

Directed evolution and rational design were used to generate active variants of toluene-4-monooxygenase (T4MO) on 2-phenylethanol (PEA), with the aim of producing hydroxytyrosol, a potent antioxidant. Due to the complexity of the enzymatic system-four proteins encoded by six genes-mutagenesis is labor-intensive and time-consuming. Therefore, the statistical model of Nov and Wein (J. Comput. Biol. 12:247-282) was used to reduce the number of variants produced and evaluated in a lab. From an initial data set of 24 variants, with mutations at nine positions, seven double or triple mutants were identified through statistical analysis. The average activity of these mutants was 4.6-fold higher than the average activity of the initial data set. In an attempt to further improve the enzyme activity to obtain PEA hydroxylation, a second round of statistical analysis was performed. Nine variants were considered, with 3, 4, and 5 point mutations. The average activity of the variants obtained in the second statistical round was 1.6-fold higher than in the first round and 7.3-fold higher than that of the initial data set. The best variant discovered, TmoA I100A E214G D285Q, exhibited an initial oxidation rate of 4.4 ± 0.3 nmol/min/mg protein, which is 190-fold higher than the rate obtained by the wild type. This rate was also 2.6-fold higher than the activity of the wild type on the natural substrate toluene. By considering only 16 preselected mutants (out of ∼13,000 possible combinations), a highly active variant was discovered with minimum time and effort.
Transformed mycosis fungoides: clinicopathological features and outcome (2007)

We believe that pathological and immunopathological documentation of progressive MF is important in order to identify T-MF early; however, the differential diagnosis is sometimes difficult. Aside from already acknowledged prognostic factors such as older age, advanced initial disease and short delay to transformation, the CD30 immunophenotype could be regarded as a useful additional prognostic marker in T-MF.
Detection of N-Glycolylneuraminic Acid-Containing Glycoproteins from Various Animal Erythrocytes by Cbicken Monoclonal Antibody against Hanganutziu-Deicher Antigens. (1994)

Two chicken monoclonal antibodies (MAbs), HU/Ch2-7 and HU/Ch6-1, detecting Hanganutziu-Deicher (HD) antigens with N-glycolylneuraminic acid (NeuGc) at a terminal carbohydrate were reactive with bovine, sheep and horse erythrocytes examined by flowcytometry (FCM). The FCM profiles of the three animal erythrocytes treated with trypsin were different from those of non-treated cells and from each other depending on MAbs used. To identify the nature of antigenic molecules, recognized by HU/Ch2-7 and HU/Ch6-1 MAbs, solubilized erythrocytes from the above three animals were analyzed by a Western blotting method. The MAb HU/Ch2-7 identified HD antigen-specific glycoprotein in each of animal erythrocytes. These results indicate that the MAb HU/Ch2-7 is a valuable reagent for the detection of NeuGc-containing gangliosides and glycoproteins.
Five-Year Survival and Correlates Among Patients With Advanced Melanoma, Renal Cell Carcinoma, or Non–Small Cell Lung Cancer Treated With Nivolumab (2019)

ClinicalTrials.gov identifier: NCT00730639.
A Monocular Vision Advance Warning System for the Automotive Aftermarket (2005)

&lt;div class="htmlview paragraph"&gt;Driver inattention and poor judgment are the major causes of motor vehicle accidents (MVA). Extensive research has shown that intelligent driver assistance systems can significantly reduce the number and severity of these accidents. The driver's visual perception abilities are a key factor in the design of the driving environment. This makes image processing a natural candidate in any effort to impact MVAs. The vision system described here encompasses 3 major capabilities: (i) Lane Departure Warning (ii) Headway Monitoring and Warning (iii) Forward Collision Warning. This paper describes in detail the different warning features, the HMI (visual and acoustic) application design rules, and results of a study in which the system was installed in a commercial fleet and passenger vehicles.&lt;/div&gt;
Successive elimination algorithm for motion estimation (1995)

The correspondence presents a fast exhaustive search algorithm for motion estimation. The basic idea is to obtain the best estimate of the motion vectors by successively eliminating the search positions in the search window and thus decreasing the number of matching evaluations that require very intensive computations. Simulation results demonstrate that although the performance of the proposed algorithm is the same as that using the exhaustive search, the computation time has been reduced significantly.
The lane recognition and vehicle detection at night for a camera-assisted car on highway (2004)

This paper presents a computer vision system for detecting lanes and vehicles on highway at night. This system recognizes the rear-lights of vehicles from the night scene image on highway, as viewed by a camera-assisted car behind. The detection of rear-lights is usually complicated by the existence of reflector plates on ground, multiple cars, and the environment lightening. The variation of the shape/size and height of rear-lights, and the wide range of possible distance from the observing vehicle also add extra complexity to the recognition. In this research, we take the approach of first detecting the reflector plates among the bright spots in the highway night scene, which indicate the lane borders. Through the brightness and area filtering, the reflector plates can be extracted. Removing the reflector spots from the bright-spot image and using the information of detected lanes, the pairing of rear-lights to find vehicles can be simplified. Experiment shows the success of this approach in detecting multiple vehicles on highway.