gebhart/patrepeval huggingface dataset:
Naturally occurring autoantibodies to skeletal proteins from human red blood cells. (1982)

The IgG fraction of sera of healthy human subjects contains natural antibodies to cytoskeletal elements of the donors own red blood cell membranes. Autoantibodies to spectrin are characterized in more detail: their Fab portion binds to the antigen. Autoantibodies, affinity-purified on immobilized spectrin band 1, precipitate 0.4 microgram of spectrin dimer per 1 microgram of autoantibody. They bind to band 1 and cross-react with band 2 of spectrin as well as with breakdown products of spectrin on blots from separated membrane polypeptides. Autoantibodies purified on spectrin band 2 after absorption on band 1 do not cross-react with band 1. The evidence strongly suggests the existence of such autoantibodies in healthy human subjects. This finding indicates that autoantibody production to normally unexposed antigens is not suppressed in ontogeny. These anti-cytoskeleton autoantibodies may have a physiologic role in clearance of debris from lysed cells. Their existence may open a new understanding of elevated anti-spectrin autoantibody concentrations in diseases with different etiologies.
Analysis of interleukin 6 gene expression in cervical neoplasia using a quantitative polymerase chain reaction assay: evidence for enhanced interleukin 6 gene expression in invasive carcinoma. (1994)

Interleukin 6 (IL-6) is a multifunctional cytokine which has recently been shown to act in vitro as a growth factor for cervical carcinoma cell lines. This prompted us to measure IL-6 gene expression using a new quantitative polymerase chain reaction assay in 13 invasive cervical cancers, 5 cases of cervical intraepithelial neoplasia, and 2 normal cervix. A significant increase in the expression of the IL-6 gene in invasive cervical carcinoma as compared to cervical intraepithelial neoplasia and normal cervix was demonstrated (P < 0.05). Unlike IL-6, the expression of other cytokine genes such as gamma-interferon was not correlated with any particular cervical histological lesion. Immunohistochemical analysis identified IL-6 protein only on stroma cells which, based on morphological criteria, most likely belong to the macrophage lineage. This was reinforced by the correlation observed between IL-6 gene expression and macrophage tumor infiltration (P < 0.007). No IL-6 immunostaining of cervical tumor cells was shown. Therefore this study confirms, in vivo, that IL-6 may play a role in the pathogenesis of carcinoma of the uterine cervix since its increased expression is associated with advanced neoplastic cervical lesions. In contrast to in vitro studies, the stromal origin of IL-6 suggests that this cytokine may modulate tumor cell proliferation by a paracrine rather than an autocrine mechanism.
Structural Basis for Peptidomimicry by a Natural Product (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructural Basis for Peptidomimicry by a Natural ProductYoshiharu Ikeda, L. Wayne Schultz, Jon Clardy, and Stuart L. SchreiberCite this: J. Am. Chem. Soc. 1994, 116, 9, 4143–4144Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 May 1994https://pubs.acs.org/doi/10.1021/ja00088a086https://doi.org/10.1021/ja00088a086research-articleACS PublicationsRequest reuse permissionsArticle Views149Altmetric-Citations25LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
Aberrantly expressed AURKC enhances the transformation and tumourigenicity of epithelial cells (2011)

Over-expression of AURKC has been detected in human colorectal cancers, thyroid carcinoma and several cancer cell lines. However, the regulation and clinical implications of over-expressed AURKC in cancer cells are unclear. Here we show that elevated AURKC increases the proliferation, transformation and migration of cancer cells. Importantly, the kinase activity of AURKC is required for these tumour-associated properties. Analysis of human cancer specimens shows that the expression of AURKC is increased in cervical cancer, and is highly correlated with staging in colorectal cancer. Over-expressed AURKC-GFP localizes to the centromeric regions of mitotic chromosomes and results in a decreased level of AURKB, a key regulator of spindle checkpoint. Expression of AURKC is down-regulated by PLZF, a transcriptional repressor, through recruitment to its promoter region. The expression levels of PLZF and AURKC mRNA display opposite patterns in human cervical and colorectal cancers. Taken together, our results provide important insights into human cancers with AURKC expression, which may serve as a potential target for cancer therapy in the future.
Myocardial Protection by Insulin at Reperfusion Requires Early Administration and Is Mediated via Akt and p70s6 Kinase Cell-Survival Signaling (2001)

The "metabolic cocktail" comprising glucose-insulin-potassium administrated at reperfusion reduces infarct size in the in vivo rat heart. We propose that insulin is the major component mediating this protection and acts via Akt prosurvival signaling. This hypothesis was studied in isolated perfused rat hearts (measuring infarct size to area of risk [%]) subjected to 35 minutes regional myocardial ischemia and 2 hours reperfusion. Insulin administered at the onset of reperfusion attenuated infarct size by >/=45% versus control hearts (P<0.001). Insulin-mediated cardioprotection was found to be independent of the presence of glucose at reperfusion. Moreover, the cell survival benefit of insulin is temporally dependent, in that insulin administration from the onset of reperfusion and maintained for either 15 minutes or for the duration of reperfusion reduced infarct size. In contrast, protection was abrogated if insulin administration was delayed until 15 minutes into reperfusion. Pharmacological inhibition of both upstream and downstream signals in the Akt prosurvival pathway abolished the cardioprotective effects of insulin. Here coadministration of insulin with the tyrosine kinase inhibitor lavendustin A, the phosphatidylinositol3-kinase (PI3-kinase) inhibitor wortmannin, and mTOR/p70s6 kinase inhibitor rapamycin abolished cardioprotection. Steady-state levels of activated/phosphorylated Akt correlated with insulin administration. Finally, downstream prosurvival targets of Akt including p70s6 kinase and BAD were modulated by insulin. In conclusion, insulin administration at reperfusion reduces myocardial infarction, is dependent on early administration during reperfusion, and is mediated via Akt and p70s6 kinase dependent signaling pathway. Moreover, BAD is maintained in its inert phosphorylated state in response to insulin therapy.
An investigation into the formation of benzo- and naphtho-pyrans by cyclisation of ortho-alkenyl(hydroxyalkyl)benzenes using either cerium(IV) ammonium nitrate or potassium t-butoxide in dimethylformamide (1984)

A series of ortho-alkenylbenzyl alcohols carrying methoxy substituents at appropriate positions on the aromatic ring have been synthesised. Each of these compounds has been treated separately with each of the title reagents.
In vitro infection of peripheral blood mononuclear cells by hepatitis C virus (1995)

To study the in vitro susceptibility of peripheral blood mononuclear cells (PBMC) to hepatitis C virus (HCV), we incubated cells from healthy donors with HCV-positive sera. Using RT-PCR and in situ hybridization, the genomic viral RNA was detected in PBMC and in their supernatants until 25 days post-incubation. The PBMC of the different donors were not all permissive to HCV, but results were more constantly positive when cells from four donors were pooled. Quantification of the genomic viral RNA by the branched-DNA assay showed a decrease in the HCV RNA concentration during the first week of culture followed by a peak during the second or third week, and also an increase in the total amount of viral RNA in the inoculated cells. Although HCV RNA could be detected in the supernatants by RT-PCR, the concentration was very low. Using a sense-specific RT-PCR method, the HCV negative-strand was also detected in the cells but not in the supernatants. In two experiments PBMC were successfully infected using HCV-positive culture supernatants, therefore suggesting that infectious particles can be produced in this system. Our findings demonstrate that PBMC are permissive for HCV replication in vitro but the replication level is very low. The HCV RNA concentration measured in PBMC of 10 chronically infected patients was not significantly higher than the maximal concentration obtained in PBMC infected in vitro.
Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma (2012)

Lenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.).
Effects of submental stimulation for several consecutive nights in patients with obstructive sleep apnoea. (1994)

Submental stimulation for five consecutive nights in patients with obstructive sleep apnoea improved the breathing disturbance, sleep quality, and daytime sleepiness. The effect lasted for the following two nights, but did not completely abolish the sleep disordered breathing.
The evolution of primary progressive apraxia of speech (2014)

Primary progressive apraxia of speech is a recently described neurodegenerative disorder in which patients present with an isolated apraxia of speech and show focal degeneration of superior premotor cortex. Little is known about how these individuals progress over time, making it difficult to provide prognostic estimates. Thirteen subjects with primary progressive apraxia of speech underwent two serial comprehensive clinical and neuroimaging evaluations 2.4 years apart [median age of onset = 67 years (range: 49-76), seven females]. All underwent detailed speech and language, neurological and neuropsychological assessments, and magnetic resonance imaging, diffusion tensor imaging and (18)F-fluorodeoxyglucose positron emission tomography at both baseline and follow-up. Rates of change of whole brain, ventricle, and midbrain volumes were calculated using the boundary-shift integral and atlas-based parcellation, and rates of regional grey matter atrophy were assessed using tensor-based morphometry. White matter tract degeneration was assessed on diffusion-tensor imaging at each time-point. Patterns of hypometabolism were assessed at the single subject-level. Neuroimaging findings were compared with a cohort of 20 age, gender, and scan-interval matched healthy controls. All subjects developed extrapyramidal signs. In eight subjects the apraxia of speech remained the predominant feature. In the other five there was a striking progression of symptoms that had evolved into a progressive supranuclear palsy-like syndrome; they showed a combination of severe parkinsonism, near mutism, dysphagia with choking, vertical supranuclear gaze palsy or slowing, balance difficulties with falls and urinary incontinence, and one was wheelchair bound. Rates of whole brain atrophy (1.5% per year; controls = 0.4% per year), ventricular expansion (8.0% per year; controls = 3.3% per year) and midbrain atrophy (1.5% per year; controls = 0.1% per year) were elevated (P ≤ 0.001) in all 13, compared to controls. Increased rates of brain atrophy over time were observed throughout the premotor cortex, as well as prefrontal cortex, motor cortex, basal ganglia and midbrain, while white matter tract degeneration spread into the splenium of the corpus callosum and motor cortex white matter. Hypometabolism progressed over time in almost all subjects. These findings demonstrate that some subjects with primary progressive apraxia of speech will rapidly evolve and develop a devastating progressive supranuclear palsy-like syndrome ∼ 5 years after onset, perhaps related to progressive involvement of neocortex, basal ganglia and midbrain. These findings help improve our understanding of primary progressive apraxia of speech and provide some important prognostic guidelines.
SLC5A8 , a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers (2003)

We identify a gene, SLC5A8, and show it is a candidate tumor suppressor gene whose silencing by aberrant methylation is a common and early event in human colon neoplasia. Aberrant DNA methylation has been implicated as a component of an epigenetic mechanism that silences genes in human cancers. Using restriction landmark genome scanning, we performed a global search to identify genes that would be aberrantly methylated at high frequency in human colon cancer. From among 1,231 genomic NotI sites assayed, site 3D41 was identified as methylated in 11 of 12 colon cancers profiled. Site 3D41 mapped to exon 1 of SLC5A8, a transcript that we assembled. In normal colon mucosa we found that SLC5A8 exon 1 is unmethylated and SLC5A8 transcript is expressed. In contrast, SLC5A8 exon 1 proved to be aberrantly methylated in 59% of primary colon cancers and 52% of colon cancer cell lines. SLC5A8 exon 1 methylated cells were uniformly silenced for SLC5A8 expression, but reactivated expression on treatment with a demethylating drug, 5-azacytidine. Transfection of SLC5A8 suppressed colony growth in each of three SLC5A8-deficient cell lines, but showed no suppressive effect in any of three SLC5A8-proficient cell lines. SLC5A8 exon 1 methylation is an early event, detectable in colon adenomas, and in even earlier microscopic colonic aberrant crypt foci. Structural homology and functional testing demonstrated that SLC5A8 is a member of the family of sodium solute symporters, which are now added as a class of candidate colon cancer suppressor genes.
Microfluidic Separation of Blood Components through Deterministic Lateral Displacement (2008)

Microfluidic devices provide a controlled platform for the manipulation and control of volumetric amounts of fluid. Primary applications of microfluidic devices include single-cell based analysis and nanoliter scale measurement of biological materials and living organisms. One method of separation of these biological components in such applications is based on size. By breaking a heterogeneous sample into several homogenous components, each individual component can be independently analyzed and/or manipulated. Deterministic lateral displacement (DLD) is an emerging technique for separating particles based on size in a microfluidic environment. This technique shows great promise as a means to continuously separate particles smaller than the feature size of a microfluidic array. As can be appreciated, particles ideally travel one of two types of path within a microfabricated array of posts depending on their size. Thus, the microfluidic device employing the DLD technique functions like a continuously operable filter, separating large from small particles, or providing particle size measurement. As a focus of this study, the separation of blood into its primary components is shown. White blood cell isolation with 100 % accuracy and separation of red blood cells and platelets from blood plasma is demonstrated through the use of the DLD. Herein is included the use of traditional blood techniques, such as the flow cytometry, to confirm these results. The DLD techniques are explored and discussed, not only for blood, but for other types of particle separations through the development, analysis and testing for four different designs. iii Acknowledgements I would like to thank my advisors Jim Sturm and Bob Austin for keeping me on track. You were always a source of new and different perspectives to every problem. I greatly appreciate all of the help from the members of the Sturm and Austin labs especially
Influence of pH on calcium influx during hypoxia in rat cortical brain slices. (1994)

These results, which differ from previous studies showing acid inhibition of calcium influx in isolated neurons, suggest that low extracellular pH may exacerbate cellular injury during severe hypoxia or ischemia in the intact brain.
Nicotinamide Benzimidazolide Dinucleotides, Non-Cyclisable Analogues of NAD+ (2014)

Benzimidazole-based nucleotides and dinucleotides have been synthesised to increase the range of chemical tools available to probe the NAD<sup>+</sup> biology space. They were examined for their reactivity in alkylation-type reactions, where they yielded unstable alkylated heteoaromatic adducts, both chemically and enzymatically. While unsuited for NAD<sup>+</sup> cyclases, these NAD<sup>+</sup> analogues could be viable substrates for non-adenine modifying NAD<sup>+</sup>-dependent enzyme classes.
Long term results of botulinum toxin type A (Dysport) in the treatment of hemifacial spasm: a report of 175 cases (1998)

This study is the first to show, in detail, the long term results of treatments of hemifacial spasm with Dysport. The efficacy is constant throughout orbicularis oculi. The efficacy of Dysport is comparable with Botox in long term follow up.
Dimerization of the ATRIP Protein through the Coiled-Coil Motif and Its Implication to the Maintenance of Stalled Replication Forks (2005)

ATR (ATM and Rad3-related), a PI kinase-related kinase (PIKK), has been implicated in the DNA structure checkpoint in mammalian cells. ATR associates with its partner protein ATRIP to form a functional complex in the nucleus. In this study, we investigated the role of the ATRIP coiled-coil domain in ATR-mediated processes. The coiled-coil domain of human ATRIP contributes to self-dimerization in vivo, which is important for the stable translocation of the ATR-ATRIP complex to nuclear foci that are formed after exposure to genotoxic stress. The expression of dimerization-defective ATRIP diminishes the maintenance of replication forks during treatment with replication inhibitors. By contrast, it does not compromise the G2/M checkpoint after IR-induced DNA damage. These results show that there are two critical functions of ATR-ATRIP after the exposure to genotoxic stress: maintenance of the integrity of replication machinery and execution of cell cycle arrest, which are separable and are achieved via distinct mechanisms. The former function may involve the concentrated localization of ATR to damaged sites for which the ATRIP coiled-coil motif is critical.
An optimized Alu-PCR primer pair for human-specific amplification of YACs and somatic cell hybrids (1992)

Journal Article An optimized Alu-PCR primer pair for human-specific amplification of YACs and somatic cell hybrids Get access Danilo A. Tagle, Danilo A. Tagle Search for other works by this author on: Oxford Academic PubMed Google Scholar Francis S. Collins Francis S. Collins 1Howard Hughes Medical Institute, Departments of Human Genetics and Internal Medicine, The University of Michigan Medical CenterAnn Arbor, Ml 48109, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 1, Issue 2, May 1992, Pages 121–122, https://doi.org/10.1093/hmg/1.2.121 Published: 01 May 1992 Article history Received: 12 February 1992 Accepted: 25 February 1992 Published: 01 May 1992
Polymeric Brushes as Functional Templates for Immobilizing Ribonuclease A:  Study of Binding Kinetics and Activity (2007)

The ability to immobilize proteins with high binding capacities on surfaces while maintaining their activity is critical for protein microarrays and other biotechnological applications. We employed poly(acrylic acid) (PAA) brushes as templates to immobilize ribonuclease A (RNase A), which is commonly used to remove RNA from plasmid DNA preparations. The brushes are grown by surface-anchored atom-transfer radical polymerization (ATRP) initiators. RNase A was immobilized by both covalent esterification and a high binding capacity metal-ion complexation method to PAA brushes. The polymer brushes immobilized 30 times more enzyme compared to self-assembled monolayers. As the thickness of the brush increases, the surface density of the RNase A increases monotonically. The immobilization was investigated by ellipsometry, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and near-edge X-ray absorption fine structure spectroscopy (NEXAFS). The activity of the immobilized RNase A was determined using UV absorbance. As much as 11.0 microg/cm(2) of RNase A was bound to PAA brushes by metal-ion complexation compared to 5.8 microg/cm(2) by covalent immobilization which is 30 and 16 times the estimated mass bound in a monolayer. The calculated diffusion coefficient D was 0.63 x 10(-14) cm(2)/s for metal-ion complexation and 0.71 x 10(-14) cm(2)/s for covalent immobilization. Similar values of D indicate that the binding kinetics is similar, but the thermodynamic equilibrium coverage varies with the binding chemistry. Immobilization kinetics and thermodynamics were characterized by ellipsometry for both methods. A maximum relative activity of 0.70-0.80 was reached between five and nine monolayers of the immobilized enzyme. However, the relative activity for covalent immobilization was greater than that of metal-ion complexation. Covalent esterification resulted in similar temperature dependence as free enzyme, whereas metal-ion complexation showed no temperature dependence indicating a significant change in conformation.
Targeted sequencing with enrichment PCR: a novel diagnostic method for the detection of EGFR mutations (2015)

Epidermal growth factor receptor (EGFR) is an important mediator of tumor cell survival and proliferation. The detection of EGFR mutations can predict prognoses and indicate when treatment with EGFR tyrosine kinase inhibitors should be used. As such, the development of highly sensitive methods for detecting EGFR mutations is important. Targeted next-generation sequencing is an effective method for diagnosing mutations. We compared the abilities of enrichment PCR followed by ultra-deep pyrosequencing (UDP), UDP alone, and PNA-mediated RT-PCR clamping to detect low-frequency EGFR mutations in tumor cell lines and tissue samples. Using enrichment PCR-UDP, we were able to detect the E19del and L858R mutations at minimum frequencies of 0.01% and 0.05%, respectively, in the PC-9 and H197 tumor cell lines. We also confirmed the sensitivity of detecting the E19del mutation by performing a titration analysis in FFPE tumor samples. The lowest mutation frequency detected was 0.0692% in tissue samples. EGFR mutations with frequencies as low as 0.01% were detected using enrichment PCR-UDP, suggesting that this method is a valuable tool for detecting rare mutations, especially in scarce tissue samples or those with small quantities of DNA.