gebhart/patrepeval huggingface dataset:
Power- and structure-variable fluorinating agents. The N-fluoropyridinium salt system (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPower- and structure-variable fluorinating agents. The N-fluoropyridinium salt systemTeruo Umemoto, Shinji Fukami, Ginjiro Tomizawa, Kikuko Harasawa, Kosuke Kawada, and Kyoichi TomitaCite this: J. Am. Chem. Soc. 1990, 112, 23, 8563–8575Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November 1990https://pubs.acs.org/doi/10.1021/ja00179a047https://doi.org/10.1021/ja00179a047research-articleACS PublicationsRequest reuse permissionsArticle Views4349Altmetric-Citations317LEARN 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
Single‐chain antibodies for the conformation‐specific blockade of activated platelet integrin α IIb β 3 designed by subtractive selection from naïve human phage libraries (2004)

Binding of fibrinogen to platelet integrin alphaIIbbeta3 mediates platelet aggregation, and thus inhibition of alphaIIbbeta3 represents a powerful therapeutic strategy in cardiovascular medicine. However, the currently used inhibitors of alphaIIbbeta3 demonstrate several adverse effects like thrombocytopenia and bleeding, which are associated with their property to bind to non-activated alphaIIbbeta3. To circumvent these problems, we designed blocking single-chain antibody-fragments (scFv) that bind to alphaIIbbeta3 exclusively in its activated conformation. Two naive phage libraries were created: a natural phage library, based on human lymphocyte cDNA, and a synthetic library, with randomized VHCDR3. We performed serial rounds of subtractive panning with depletion on non-activated and selection on activated alphaIIbbeta3, which were provided on resting and ADP-stimulated platelets and CHO cells, expressing wild-type or mutated and thereby activated alphaIIbbeta3. In contrast to isolated, immobilized targets, as generally used for phage display, this unique cell-based approach for panning allowed the preservation of functional integrin conformation. Thereby, we obtained several scFv-clones that demonstrated exclusive binding to activated platelets and complete inhibition of fibrinogen binding and platelet aggregation. Interestingly, all activation-specific clones contained an RXD pattern in the HCDR3. Binding studies on transiently expressed point mutants and mouse-human domain-switch mutants of alphaIIbbeta3 indicate a binding site similar to fibrinogen. In conclusion, we generated human activation-specific scFvs against alphaIIbbeta3, which bind selectively to activated alphaIIbbeta3 and thereby potently inhibit fibrinogen binding to alphaIIbbeta3 and platelet aggregation.
A codon 338 nonsense mutation in the factor IX gene in unrelated hemophilia B patients: factor IX338 New York (1989)

Hemophilia B is an X-linked recessive bleeding disorder resulting from a deficiency of the coagulation factor IX (FIX) protein activity, a vitamin K-dependent serine protease active in both the intrinsic and extrinsic coagulation systems. DNA analyses of the factor IX gene in two unrelated patients with severe hemophilia B, with a IX coagulant activity less than 1% and undetectable FIX antigen, detected the loss of the second TaqI site in exon h (VIII) in both individuals. Polymerase chain reaction (PCR) amplification of 576 base pairs of exon h (VIII) with cloning and dideoxy sequencing of cloned DNA from one hemophiliac revealed a single C----T transition in codon 338 that changes an arginine residue codon CGA to a nonsense codon TGA. Allele- specific oligonucleotide probe hybridization with a mutant (C----T) and a wild-type allele confirmed the same mutation in amplified genomic DNA of the second hemophilia patient. The C----T transition represents another example of mutation at a CpG dinucleotide. DNA polymorphism analysis of the FIX gene in both individuals revealed each to be on a separate FIX haplotype; therefore, predicting each to be a separate mutation event.
Use of capture-based next-generation sequencing to detect ALK fusion in plasma cell-free DNA of patients with non-small-cell lung cancer (2016)

Capture-based next-generation sequencing (NGS) is a potentially useful diagnostic method to measure tumor tissue DNA in blood as it can identify concordant mutations between cell-free DNA (cfDNA) and primary tumor DNA in lung cancer patients. In this study, the sensitivity, specificity and accuracy of capture-based NGS for detecting ALK fusion in plasma cfDNA was assessed. 24 patients with tissue ALK-positivity and 15 who did not harbor ALK fusion were enrolled. 13 ALK-positive samples were identified by capture-based NGS among the 24 samples with tissue ALK-positivity. In addition to EML4-ALK, 2 rare fusion types (FAM179A-ALK and COL25A1-ALK) were also identified. The overall sensitivity, specificity and accuracy for all cases were 54.2%, 100% and 71.8%, respectively. For patients without distant metastasis (M0-M1a) and patients with distant metastasis (M1b), the sensitivities were 28.6% and 64.7%, respectively. In the 15 patients who received crizotinib, the estimated median PFS was 9.93 months. Thus, captured-based NGS has acceptable sensitivity and excellent specificity for the detection of ALK fusion in plasma cfDNA, especially for patients with distant metastasis. This non-invasive method is clinically feasible for detecting ALK fusion in patients with advanced-stage NSCLC who cannot undergo traumatic examinations or have insufficient tissue samples for molecular tests.
MPprimer: a program for reliable multiplex PCR primer design (2010)

MPprimer is a valuable tool for designing specific, non-dimerizing primer set combinations with constrained amplicons size for multiplex PCR assays.
FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development (1998)

During early tooth development, multiple signaling molecules are expressed in the dental lamina epithelium and induce the dental mesenchyme. One signal, BMP4, has been shown to induce morphologic changes in dental mesenchyme and mesenchymal gene expression via Msx1, but BMP4 cannot substitute for all the inductive functions of the dental epithelium. To investigate the role of FGFs during early tooth development, we examined the expression of epithelial and mesenchymal Fgfs in wild-type and Msx1 mutant tooth germs and tested the ability of FGFs to induce Fgf3 and Bmp4 expression in wild-type and Msx1 mutant dental mesenchymal explants. Fgf8 expression is preserved in Msx1 mutant epithelium while that of Fgf3 is not detected in Msx1 mutant dental mesenchyme. Moreover, dental epithelium as well as beads soaked in FGF1, FGF2 or FGF8 induce Fgf3 expression in dental mesenchyme in an Msx1-dependent manner. These results indicate that, like BMP4, FGF8 constitutes an epithelial inductive signal capable of inducing the expression of downstream signaling molecules in dental mesenchyme via Msx1. However, the BMP4 and FGF8 signaling pathways are distinct. BMP4 cannot induce Fgf3 nor can FGFs induce Bmp4 expression in dental mesenchyme, even though both signaling molecules can induce Msx1 and Msx1 is necessary for Fgf3 and Bmp4 expression in dental mesenchyme. In addition, we have investigated the effects of FGFs and BMP4 on the distal-less homeobox genes Dlx1 and Dlx2 and we have clarified the relationship between Msx and Dlx gene function in the developing tooth. Dlx1,Dlx2 double mutants exhibit a lamina stage arrest in maxillary molar tooth development (Thomas B. L., Tucker A. S., Qiu M. , Ferguson C. A., Hardcastle Z., Rubenstein J. L. R. and Sharpe P. T. (1997) Development 124, 4811-4818). Although the maintenance of molar mesenchymal Dlx2 expression at the bud stage is Msx1-dependent, both the maintenance of Dlx1 expression and the initial activation of mesenchymal Dlx1 and Dlx2 expression during the lamina stage are not. Moreover, in contrast to the tooth bud stage arrest observed in Msx1 mutants, Msx1,Msx2 double mutants exhibit an earlier phenotype closely resembling the lamina stage arrest observed in Dlx1,Dlx2 double mutants. These results are consistent with functional redundancy between Msx1 and Msx2 in dental mesenchyme and support a model whereby Msx and Dlx genes function in parallel within the dental mesenchyme during tooth initiation. Indeed, as predicted by such a model, BMP4 and FGF8, epithelial signals that induce differential Msx1 and Msx2 expression in dental mesenchyme, also differentially induce Dlx1 and Dlx2 expression, and do so in an Msx1-independent manner. These results integrate Dlx1, Dlx2 and Fgf3 and Fgf8 into the odontogenic regulatory hierarchy along with Msx1, Msx2 and Bmp4, and provide a basis for interpreting tooth induction in terms of transcription factors which, individually, are necessary but not sufficient for the expression of downstream signals and therefore must act in specific combinations.
The FAM Deubiquitylating Enzyme Localizes to Multiple Points of Protein Trafficking in Epithelia, where It Associates with E-cadherin and β-catenin (2004)

Ubiquitylation is a necessary step in the endocytosis and lysosomal trafficking of many plasma membrane proteins and can also influence protein trafficking in the biosynthetic pathway. Although a molecular understanding of ubiquitylation in these processes is beginning to emerge, very little is known about the role deubiquitylation may play. Fat Facets in mouse (FAM) is substrate-specific deubiquitylating enzyme highly expressed in epithelia where it interacts with its substrate, beta-catenin. Here we show, in the polarized intestinal epithelial cell line T84, FAM localized to multiple points of protein trafficking. FAM interacted with beta-catenin and E-cadherin in T84 cells but only in subconfluent cultures. FAM extensively colocalized with beta-catenin in cytoplasmic puncta but not at sites of cell-cell contact as well as immunoprecipitating with beta-catenin and E-cadherin from a higher molecular weight complex ( approximately 500 kDa). At confluence FAM neither colocalized with, nor immunoprecipitated, beta-catenin or E-cadherin, which were predominantly in a larger molecular weight complex ( approximately 2 MDa) at the cell surface. Overexpression of FAM in MCF-7 epithelial cells resulted in increased beta-catenin levels, which localized to the plasma membrane. Expression of E-cadherin in L-cell fibroblasts resulted in the relocalization of FAM from the Golgi to cytoplasmic puncta. These data strongly suggest that FAM associates with E-cadherin and beta-catenin during trafficking to the plasma membrane.
Decreased Hepatic Glutathione Levels in Septic Shock (1985)

Intracellular metabolite glutathione, existing in either its reduced (GSH) or oxidized states, is crucial for the protection of any cell against an oxidative stress or injury. Significant depletion of intracellular levels of GSH predisposes cells to an oxidative injury. We have investigated the level of hepatic GSH during the early course of sepsis in a physiologically well-characterized septic-sheep model. Following six hours of sepsis, which was characterized by hypotension, hypoxemia, and granulocytopenia, the level of intrahepatic GSH was significantly reduced compared with baseline levels. There was no reduction after two hours of sepsis. Hepatic GSH levels in control animals were unchanged compared with baseline levels. These findings suggest that the liver may be more susceptible to an oxidative stress in septic patients.
Nursing is not a 'textbook' profession (1996)

I am writing to ask why nursing is seen as a very ‘textbook’ style profession?
Circulating and Tissue Endothelin Immunoreactivity in Advanced Atherosclerosis (1991)

Endothelin may be a marker for arterial vascular disease. Whether it participates in the atherogenic process or is merely released from damaged endothelial cells is unclear.
Wi-Fi RF energy harvesting for battery-free wearable radio platforms (2015)

Wearable devices have huge market potential, but their usage has been limited because means to power such devices is still a challenge. Batteries, the most widespread solution, add size, weight and need periodic recharging which is a huge deterrent. In this work, we propose to eliminate batteries by leveraging Wi-Fi transmissions from nearby devices such as access points and smart phones to deliver power wirelessly to wearable devices. We develop a wearable temperature sensor, which harvests energy from Wi-Fi transmissions and transmits data back to an access point. We enable this application by designing an efficient 2.4 GHz Wi-Fi harvesting front-end to power an ANT radio platform with a smartphone as the Wi-Fi source. We study and analyze the effect of OFDM modulation, wide bandwidth (72 MHz) and the bursty nature of 802.11 Wi-Fi signals on the sensitivity, efficiency and the output power of the RF harvester. Our prototype achieves a sensitivity of -16.5 dBm with 100 % duty cycle Wi-Fi transmissions for a target output voltage of 2.05 V and 2.5 μW leakage at the storage capacitor node. This translates to an operating range of about 11.5 cm from a 2 dBm Wi-Fi transmitter on a smartphone and 92 cm from a 20 dBm Wi-Fi access point with a 3 dBi antenna on the wearable device.
Expression of Melanoma Antigen-Encoding Genes (MAGE) by Common Primers for MAGE-A1 to -A6 in Colorectal Carcinomas Among Koreans (2002)

This study was to investigate Melanoma-antigen gene (MAGE) expression by reverse transcription-nested polymerase chain reaction (RT-nested PCR) with the original common primers of MAGE-A1 to -A6 and analysis of correlation between its expression and the well-known clinical parameters in addition to evaluate the clinical feasibility of the common primers. Surgical tumor and corresponding nonneoplastic tissue samples from 38 patients with colorectal cancer were studied. To confirm the identities of RT-PCR products, direct sequencing was done after in vitro subcloning. No expression of MAGE was observed in the non-neoplastic colorectal mucosal tissues. Sixteen (42.1%) of 38 carcinomas expressed at least one of MAGE A-1 to -6. The expression of the MAGE genes was not related to age, sex, histological grades, the depth of invasion, metastasis to lymph nodes, vessel, neural, or perineural invasion. The identities with the corresponding mRNAs were confirmed in 6 cases for MAGE-A2 (15.8%), 6 cases for MAGE-A4 (15.8%), 2 cases for MAGE-A3 (5.3%), and one case for MAGE A-6 (2.6%). These results suggest that MAGE expressions, except those of MAGE-A2 and -A4, seem to have a limited role in the molecular pathogenesis of colon cancer. However, the common primer sets to detect of expressions for MAGE-A1 to -A6 simultaneously appear to be feasible to differentiate malignant from benign lesions in colorectal diseases.
A clinical pathological comparison of three families with frontotemporal dementia and identical mutations in the tau gene (P301L) (1999)

We investigated three separate families (designated D, F and G) with frontotemporal dementia that have the same molecular mutation in exon 10 of the tau gene (P301L). The families share many clinical characteristics, including behavioural aberrations, defective executive functions, language deficits, relatively preserved constructional abilities and frontotemporal atrophy on imaging studies. However, Family D has an earlier mean age of onset and shorter duration of disease than Families F and G (49.0 and 5.1 years versus 61-64 and 7.3-8.0 years, respectively). Two members of Families D and F had neuropathological studies demonstrating lobar atrophy, but the brain from Family D had prominent and diffuse circular, intraneuronal, neurofibrillary tangles not seen in Family F. The brain from Family F had ballooned neurons typical of Pick's disease type B not found in Family D. A second autopsy from Family D showed neurofibrillary tangles in the brainstem with a distribution similar to that found in progressive supranuclear palsy. These three families demonstrate that a missense mutation in the exon 10 microtubule-binding domain of the tau protein gene can produce severe behavioural abnormalities with frontotemporal lobar atrophy and microscopic tau pathology. However, the findings in these families also emphasize that additional unidentified environmental and/or genetic factors must be producing important phenotypic variability on the background of an identical mutation. Apolipoprotein E genotype does not appear to be such a factor influencing age of onset in this disease.
Broadened immunity against influenza by vaccination with computationally designed influenza virus N1 neuraminidase constructs (2018)

Split inactivated influenza vaccines remain one of the primary preventative strategies against severe influenza disease in the population. However, current vaccines are only effective against a limited number of matched strains. The need for broadly protective vaccines is acute due to the high mutational rate of influenza viruses and multiple strain variants in circulation at any one time. The neuraminidase (NA) glycoprotein expressed on the influenza virion surface has recently regained recognition as a valuable vaccine candidate. We sought to broaden the protection provided by NA within the N1 subtype by computationally engineering consensus NA sequences. Three NA antigens (NA5200, NA7900, NA9100) were designed based on sequence clusters encompassing three major groupings of NA sequence space; (i) H1N1 2009 pandemic and Swine H1N1, (ii) historical seasonal H1N1 and (iii) H1N1 viruses ranging from 1933 till current times. Recombinant NA proteins were produced as a vaccine and used in a mouse challenge model. The design of the protein dictated the protection provided against the challenge strains. NA5200 protected against H1N1 pdm09, a Swine isolate from 1998 and NIBRG-14 (H5N1). NA7900 protected against all seasonal H1N1 viruses tested, and NA9100 showed the broadest range of protection covering all N1 viruses tested. By passive transfer studies and serological assays, the protection provided by the cluster-based consensus (CBC) designs correlated to antibodies capable of mediating NA inhibition. Importantly, sera raised to the consensus NAs displayed a broader pattern of reactivity and protection than naturally occurring NAs, potentially supporting a predictive approach to antigen design.
Screening for pain phenotypes: Analysis of three congenic mouse strains on a battery of nine nociceptive assays (2006)

In an attempt to identify new genes responsible for variability in pain sensitivity, we tested three congenic mouse strains--in which a small portion of the genome of the MOLF/Ei strain has been placed on a C57BL/6 genetic background--on a battery of nine nociceptive assays, chosen to reflect those assays in most common use in the pain literature. Mice of both sexes were evaluated by two different testers at different points in time, allowing us to examine the relative importance of genotype, sex, tester and cohort effects on data from these assays. We find strong evidence for the existence of two quantitative trait loci (i.e., genomic regions containing variability-causing genes), one for thermal nociception on mouse chromosome (Chr) 17 (Chr 17; Tpnr3) and one for formalin test nociception on mouse Chr 12 (Nociq3). We note, however, that the nociceptive assays in this battery feature strong main effects and interactions of sex, tester, and cohort, which if not controlled or covaried can seriously confound interpretation of genetic experiments, including the comparison of transgenic knockout mice to their wild-type controls.
Nuclear pre-mRNA processing in plants: distinct modes of 3'-splice-site selection in plants and animals. (1988)

The report that human growth hormone pre-mRNA is not processed in transgenic plant tissues (A. Barta, K. Sommergruber, D. Thompson, K. Hartmuth, M.A. Matzke, and A.J.M. Matzke, Plant Mol. Biol. 6:347-357, 1986) has suggested that differences in mRNA splicing processes exist between plants and animals. To gain more information about the specificity of plant pre-mRNA processing, we have compared the splicing of the soybean leghemoglobin pre-mRNA with that of the human beta-globin pre-mRNA in transfected plant (Orychophragmus violaceus and Nicotiana tabacum) protoplasts and mammalian (HeLa) cells. Of the three introns of leghemoglobin pre-mRNA, only intron 2 was correctly and efficiently processed in HeLa cells. The 5' splice sites of the remaining two introns were faithfully recognized, but correct processing of the 3' sites took place only rarely (intron 1) or not at all (intron 3); cryptic 3' splice sites were used instead. While the first intron in human beta-globin pre-mRNA was not spliced in transfected plant protoplasts, intron 2 processing occurred at a low level, indicating that some mammalian introns can be recognized by the plant intron-splicing machinery. However, excision of intron 2 proved to be incorrect, involving the authentic 5' splice site and a cryptic 3' splice site. Our results indicate that the mechanism of 3'-splice-site selection during intron excision differs between plants and animals. This conclusion is supported by analysis of the 3'-splice-site consensus sequences in animal and plant introns which revealed that polypyrimidine tracts, characteristic of animal introns, are not present in plant pre-mRNAs. It is proposed that an elevated AU content of plant introns is important for their processing.
Vaccination preventsHelicobacter pylori-induced alterations of the gastric flora in mice (2006)

Molecular analysis of the gastric microflora in mice revealed that Helicobacter pylori infection causes an increase in microbial diversity. The stomachs of H. pylori-infected animals were colonized by bacteria which are naturally restricted to the lower intestinal tract. Clostridia, Bacteroides/Prevotella spp., Eubacterium spp., Ruminococcus spp., streptococci and Escherichia coli were detected exclusively in the stomachs of infected animals, whereas lactobacilli dominated the gastric flora in noninfected mice. The H. pylori-induced shifts in the gastric microbiota were independent from histological pathology and from changes in the gastric pH but were prevented by immunization of mice with live Salmonella expressing H. pylori urease. Immunized mice displayed reduced H. pylori levels in the gastric epithelium and developed a normal gastric microflora, indicating that vaccination may be protective against H. pylori-induced changes in the gastric flora.