gebhart/patrepeval huggingface dataset:
Triple Layer Control: Phosphorylation, Acetylation and Ubiquitination of FOXO Proteins (2005)

FOXO proteins are transcriptional regulators that control cell cycle progression, DNA repair, defense against oxidative damage and apoptosis. These divergent functions of FOXO proteins are regulated by signal-induced, post-translational modifications. Phosphorylation of cytoplasmic FOXO at specific sites by JNK initiates translocation into the nucleus. Acetylation and deacetylation of nuclear FOXO affects the selection of transcriptional programs that are controlled by FOXO proteins. Activation of Akt by growth factors results in phosphorylation of nuclear FOXO at specific sites followed by additional phosphorylations mediated by other kinases. Akt-dependent phosphorylation reduces the DNA-binding activity of FOXO, interferes with binding to the co-activators p300/CBP, and inactivates the FOXO nuclear translocation signal. The Akt-phosphorylated FOXO is exported from the nucleus in a CRM1- and 14-3-3-dependent process. Cytoplasmic, Akt-phosphorylated FOXO interacts with the ubiquitin ligase Skp2 and is targeted for proteasomal degradation. The nuclear-cytoplasmic "FOXO shuttle" is driven by stress signals that result in nuclear import and FOXO transcriptional activity and growth signals that initiate nuclear export and proteasomal degradation of FOXO.
Neural controller for adaptive movements with unforeseen payloads (1990)

A theory and computer simulation of a neural controller that learns to move and position a link carrying an unforeseen payload accurately are presented. The neural controller learns adaptive dynamic control from its own experience. It does not use information about link mass, link length, or direction of gravity, and it uses only indirect uncalibrated information about payload and actuator limits. Its average positioning accuracy across a large range of payloads after learning is 3% of the positioning range. This neural controller can be used as a basis for coordinating any number of sensory inputs with limbs of any number of joints. The feedforward nature of control allows parallel implementation in real time across multiple joints.
Improved Boolean function hashing based on multiple-vertex dominators (2005)

The growing complexity of today's system designs requires fast and robust verification methods. Existing BDD, SAT or ATPG-based techniques do not provide sufficient solutions for many verification instances. Boolean function hashing is a probabilistic verification approach which can complement existing formal methods in a number of applications such as equivalence checking, biased random simulation, power analysis and power optimization. The proposed hashing technique is based on the arithmetic transform, which maps a Boolean function onto a probabilistic hash value for a given input assignment. The presented algorithm uses multiple-vertex dominators in circuit graphs to progressively simplify intermediate hashing steps. The experimental results on benchmark circuits demonstrate the robustness of our approach.
Acute Myocardial Infarction in 258 Cases of Diabetes (1965)

THIS is a study of 258 hospitalized diabetic patients who sustained acute myocardial infarction. The data deal with the immediate mortality of the acute attack and the five-year survival among those who recovered from it, as well as with various associated and prognostic factors. The findings are compared with previously reported similar studies of diabetic patients and the general population.Materials and MethodsAll 258 patients had diabetes mellitus and were admitted with acute myocardial infarction to the Joslin Clinic Service of the New England Deaconess Hospital in Boston during a five-year period from 1954 to 1958. The criteria for . . .
Two New Candidate Adenovirus Serotypes (1993)

Two new adenovirus (AV) subgenus D serotypes, which we propose as AV candidates 48 and 49, are described. Both AV 48 and 49 were unique by serum neutralization and the pattern of restriction endonuclease fragments. By the hemagglutination inhibition assay there was a significant reciprocal cross between AV 48 and 44 and one-way crosses between AV 48 and AV 37 sera and between AV 30 and AV 49 sera. Eleven AV 48 and 5 AV 49 isolates, mainly from AIDS patients, have been identified at the Viral and Rickettsial Disease Laboratory.
Against a Whole-Genome Shotgun (1997)

The human genome project is entering its decisive final phase, in which the genome sequence will be determined in large-scale efforts in multiple laboratories worldwide. A number of sequencing groups are in the process of scaling up their throughput; over the next few years they will need to attain a collective capacity approaching half a gigabase per year to complete the 3-Gb genome sequence by the target date of 2005. At present, all contributing groups are using a clone-by-clone approach, in which mapped bacterial clones (typically 40-400 kb in size) from known chromosomal locations are sequenced to completion. Among other advantages, this permits a variety of alternative sequencing strategies and methods to be explored independently without redundancy of effort. Although it is not too late to consider implementing a different approach, any such approach must have as high a probability of success as the current one and offer significant advantages (such as decreased cost). I argue here that the whole-genome shotgun proposed by Weber and Myers satisfies neither condition.
Intravenous Iron Dextran in Clinical Medicine (1980)

Four hundred seventy-one adult patients and ten adult prisoner volunteers received 2,099 intravenous (IV) injections of iron dextran (Imferon), usually 250 to 500 mg at less than 100 mg/min. Intravenous iron supplies enough iron to permit RBC formation greater than 50 mL/day and repletion of tissue iron. Tissue iron did not always supply iron at an optimal rate. Hemoglobin production was higher after IV than oral or intramuscular iron if the hemoglobin level was less than 9 g/dL. Three life-threatening immediate anaphylactoid and eight severe delayed reactions were observed. There were no deaths. Delayed reactions were more frequent in women and collagen-vascular diseases and less frequent in pregnancy. Because anaphylactoid reactions are serious and unpredictable, IV iron dextran should be used only when iron deficiency anemia cannot be treated adequately with oral iron.
Efficient Mutagenesis by Cas9 Protein-Mediated Oligonucleotide Insertion and Large-Scale Assessment of Single-Guide RNAs (2014)

The CRISPR/Cas9 system has been implemented in a variety of model organisms to mediate site-directed mutagenesis. A wide range of mutation rates has been reported, but at a limited number of genomic target sites. To uncover the rules that govern effective Cas9-mediated mutagenesis in zebrafish, we targeted over a hundred genomic loci for mutagenesis using a streamlined and cloning-free method. We generated mutations in 85% of target genes with mutation rates varying across several orders of magnitude, and identified sequence composition rules that influence mutagenesis. We increased rates of mutagenesis by implementing several novel approaches. The activities of poor or unsuccessful single-guide RNAs (sgRNAs) initiating with a 5' adenine were improved by rescuing 5' end homogeneity of the sgRNA. In some cases, direct injection of Cas9 protein/sgRNA complex further increased mutagenic activity. We also observed that low diversity of mutant alleles led to repeated failure to obtain frame-shift mutations. This limitation was overcome by knock-in of a stop codon cassette that ensured coding frame truncation. Our improved methods and detailed protocols make Cas9-mediated mutagenesis an attractive approach for labs of all sizes.
4,4-Disubstituted Piperidines: A New Class of NK1 Antagonists (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT4,4-Disubstituted Piperidines: A New Class of NK1 AntagonistsGraeme I. Stevenson, Angus M. MacLeod, Ian Huscroft, Margaret A. Cascieri, Sharon Sadowski, and Raymond BakerCite this: J. Med. Chem. 1995, 38, 8, 1264–1266Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://doi.org/10.1021/jm00008a003Request reuse permissionsArticle Views151Altmetric-Citations20LEARN 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 InReddit PDF (309 KB) Get e-Alertsclose Get e-Alerts
Transgenic expression of a GFP-rhodopsin COOH-terminal fusion protein in zebrafish rod photoreceptors (2002)

To facilitate the identification and characterization of mutations affecting the retina and photoreceptors in the zebrafish, a transgene expressing green fluorescent protein (GFP) fused to the C-terminal 44 amino acids of Xenopus rhodopsin (Tam et al., 2000) under the control of the 1.3-kb proximal Xenopus opsin promoter was inserted into the zebrafish genome. GFP expression was easily observed in a ventral patch of retinal cells at 4 days postfertilization (dpf). Between 45-50% of the progeny from the F1, F2, and F3 generations expressed the transgene, consistent with a single integration event following microinjection. Immunohistochemical analysis demonstrated that GFP is expressed exclusively in rod photoreceptors and not in the UV, blue, or red/green double cones. Furthermore, GFP is localized to the rod outer segments with little to no fluorescence in the rod inner segments, rod cell bodies, or rod synapse regions, indicating proper targeting and transport of the GFP fusion protein. Application of exogenous retinoic acid (RA) increased the number of GFP-expressing cells throughout the retina, and possibly the level of expressed rhodopsin. When bred to a zebrafish rod degeneration mutant, fewer GFP-expressing rods were seen in living mutants as compared to wild-type siblings. This transgenic line will facilitate the search for recessive and dominant mutations affecting rod photoreceptor development and survival as well as proper rhodopsin expression, targeting, and transport.
Immunoregulatory Molecule B7-H1 (CD274) Contributes to Skin Carcinogenesis (2011)

B7-H1 (CD274), a member of the B7 family of coinhibitory molecules, is often induced in human tumors and its expression is closely correlated with a poor prognosis or higher malignancy grade. Tumor-associated B7-H1 is implicated in mechanisms of immune escape. Under inflammatory conditions, B7-H1 is also inducible in normal epithelial cells, but little is known about its involvement in the conversion of normal cells to tumor cells. We recently found that skin-specific expression of B7-H1 accelerates chemically induced carcinogenesis of squamous cell carcinoma (SCC), despite impaired skin inflammatory responses, in B7-H1 transgenic (B7-H1tg) mice. B7-H1tg-derived keratinocytes (KC) and SCCs exhibited a marked reduction of E-cadherin, and B7-H1tg-originated SCCs showed elevated expression of the transcription factors Slug and Twist, suggesting that B7-H1 overexpression in KCs promotes the epithelial-mesenchymal transition and accelerates carcinogenesis. This review discusses the diverse functions of B7-H1 in carcinogenesis and cancer progression, and considers future directions for developing cancer therapy targeting B7-H1.
Expression of Novel Alzheimer’s Disease Risk Genes in Control and Alzheimer’s Disease Brains (2012)

Late onset Alzheimer's disease (LOAD) etiology is influenced by complex interactions between genetic and environmental risk factors. Large-scale genome wide association studies (GWAS) for LOAD have identified 10 novel risk genes: ABCA7, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, MS4A6A, MS4A6E, and PICALM. We sought to measure the influence of GWAS single nucleotide polymorphisms (SNPs) and gene expression levels on clinical and pathological measures of AD in brain tissue from the parietal lobe of AD cases and age-matched, cognitively normal controls. We found that ABCA7, CD33, and CR1 expression levels were associated with clinical dementia rating (CDR), with higher expression being associated with more advanced cognitive decline. BIN1 expression levels were associated with disease progression, where higher expression was associated with a delayed age at onset. CD33, CLU, and CR1 expression levels were associated with disease status, where elevated expression levels were associated with AD. Additionally, MS4A6A expression levels were associated with Braak tangle and Braak plaque scores, with elevated expression levels being associated with more advanced brain pathology. We failed to detect an association between GWAS SNPs and gene expression levels in our brain series. The minor allele of rs3764650 in ABCA7 is associated with age at onset and disease duration, and the minor allele of rs670139 in MS4A6E was associated with Braak tangle and Braak plaque score. These findings suggest that expression of some GWAS genes, namely ABCA7, BIN1, CD33, CLU, CR1 and the MS4A family, are altered in AD brains.
Interleaved polarization division multiplexing in self-homodyne coherent WDM systems (2010)

We demonstrate increased spectral efficiency for self-homodyne coherent WDM systems by using a novel interleaved polarization division multiplexing scheme.
Lgr5-Expressing Cells Are Sufficient and Necessary for Postnatal Mammary Gland Organogenesis (2013)

Mammary epithelial stem cells are vital to tissue expansion and remodeling during various phases of postnatal mammary development. Basal mammary epithelial cells are enriched in Wnt-responsive cells and can reconstitute cleared mammary fat pads upon transplantation into mice. Lgr5 is a Wnt-regulated target gene and was identified as a major stem cell marker in the small intestine, colon, stomach, and hair follicle, as well as in kidney nephrons. Here, we demonstrate the outstanding regenerative potential of a rare population of Lgr5-expressing (Lgr5(+)) mammary epithelial cells (MECs). We found that Lgr5(+) cells reside within the basal population, are superior to other basal cells in regenerating functional mammary glands (MGs), are exceptionally efficient in reconstituting MGs from single cells, and exhibit regenerative capacity in serial transplantations. Loss-of-function and depletion experiments of Lgr5(+) cells from transplanted MECs or from pubertal MGs revealed that these cells are not only sufficient but also necessary for postnatal mammary organogenesis.
Humoral immune responses of cancer patients against “Cancer-Testis” antigen NY-ESO-1: Correlation with clinical events (1999)

Humoral immune responses against the "Cancer-Testis" (CT) antigen NY-ESO-1 are frequently observed in patients with NY-ESO-1 expressing tumors. This is in contrast to other known tumor antigens (TA) defined by antibody or cytotoxic T cell (CTL) reactivity, i.e., MAGE-1, MAGE-3, SSX2, Melan A, and tyrosinase. No NY-ESO-1 antibody has been detected in healthy controls and patients with NY-ESO-1 negative tumors. In this study, we have assessed the NY-ESO-1 serum antibody response in patients with NY-ESO-1 positive tumors of different histological types and stages using Western blotting and an ELISA. Of the 12 patients analyzed, 10 had demonstrable NY-ESO-1 antibodies at the start of the study. All patients were followed for changes in NY-ESO-1 antibody titers during the course of tumor treatment and clinical evolution. In 4 patients, an increase of NY-ESO-1 antibody titer was observed with progression of disease or extensive tumor necrosis under treatment. One patient showed a stable NY-ESO-1 antibody titer over 3 years along with gradual regression of a large tumor mass. In 5 patients, a decrease of NY-ESO-1 antibody was detected: in 1 patient after curative tumor resection, in 3 patients with partial regression of metastatic disease under chemo- and immunotherapy, and in another patient with a NY-ESO-1 negative tumor relapse. Our results indicate that the induction and maintenance of NY-ESO-1 antibody is dependent on the presence of NY-ESO-1 expressing tumors. Furthermore, changes in NY-ESO-1 antibody titers correlate with the evolution of NY-ESO-1 positive disease.
Drosophila NK-homeobox genes. (1989)

Four Drosophila melanogaster homeobox genes were found by screening a genomic DNA library with oligodeoxynucleotides that correspond to a conserved amino acid sequence that is part of the putative of homeobox proteins that recognizes nucleotide sequences in DNA. The amino acid sequences of NK-2, NK-3, and NK-4 homeoboxes are more closely related to one another (59-66% homology) than they are to other Drosophila homeoboxes (28-54% homology), whereas the homeobox of NK-1 is most closely related, in order of decreasing homology, to muscle segment homeobox, zerknüllt-1, NK-3, and distal-less homeoboxes. Three of the genes, NK-1, NK-3, and NK-4, comprise a cluster of homeobox genes located in the 93E1-5 region of the right arm of the third chromosome, whereas the fourth homeobox gene, NK-2, is located in the 1C1-5 region of the X chromosome.
Soluble Aluminum Silicates: Stoichiometry, Stability, and Implications for Environmental Geochemistry (1992)

Soluble aluminum silicate (Al-Si) complexes are critical species for the development and application of geochemical models. A fluorescence probe technique was used to show that Al-Si complexes account for up to 95% of the total inorganic mononuclear Al in natural waters. The presence of these soluble Al-Si species affects the solubility of Al-Si minerals. Soluble Al-Si species may be important intermediates in the weathering reactions of primary Al-Si minerals and should be considered in dissolution models. Soluble Al-Si species may be key components controlling the formation of metastable and new stable minerals during interactions between water and rocks or soils.
Expression and Function of the Receptor Protein Tyrosine Phosphatase ζ and Its Ligand Pleiotrophin in Human Astrocytomas (2003)

Using subtractive cloning combined with cDNA array analysis, we previously identified the genes encoding for the protein tyrosine phosphatase zeta/receptor-type protein tyrosine phosphatase beta (PTPzeta/RPTPbeta) and its ligand pleiotrophin (PTN) as overexpressed in human glioblastomas compared to normal brain. Both molecules have been implicated in neuronal migration during central nervous system development, and PTN is known to be involved in tumor growth and angiogenesis. We confirm overexpression of both molecules at the protein level in astrocytic gliomas of different malignancy grades. PTPzeta/RPTPbeta immunoreactivity was associated with increasing malignancy grade and localized predominantly to the tumor cells. PTN immunoreactivity as determined by ELISA and immunohistochemistry analysis was increased in low-grade astrocytomas compared to normal brain. Further increase in malignant gliomas was marginal, and thus no correlation with malignancy grade or microvessel density was present. However, PTN levels were significantly associated with those of fibroblast growth factor-2, suggesting co-regulation of both factors. Functionally, PTN induced weak chemotactic and strong haptotactic migration of glioblastoma and cerebral microvascular endothelial cells. Haptotaxis of glioblastoma cells towards PTN was specifically inhibited by an anti-PTPzeta/RPTPbeta antibody. Our findings suggest that upregulated expression of PTN and PTPzeta/RPTPbeta in human astrocytic tumor cells can create an autocrine loop that is important for glioma cell migration. Although PTN is a secreted growth factor, it appears to exert its mitogenic effects mostly in a matrix-immobilized form, serving as a substrate for migrating tumor cells.
STUDIES ON THE PROPAGATION IN VITRO OF POLIOMYELITIS VIRUSES (1953)

The cells of a human epithelial cancer cultivated en masse have been shown to support the multiplication of all three types of poliomyelitis virus. These cells (strain HeLa of Gey) have been maintained in vitro since their derivation from an epidermoid carcinoma of the cervix in February, 1951. As the virus multiplied it caused in from 12 to 96 hours degeneration and destruction of the cancer cells. The specific destructive effect of the virus was prevented by adding homotypic antibody to the cultures but not by adding heterotypic antibodies. Methods for the preparation of large numbers of replicate cultures with suspensions of strain HeLa cells were described. The cells in suspension were readily quantitated by direct counts in a hemocytometer. A synthetic solution that maintains cellular viability was employed for viral propagation. The experimental results demonstrate the usefulness of strain HeLa cells for (a) the quantitation of poliomyelitis virus, (b) the measurement of poliomyelitis antibodies, and (c) the production of virus.
limma powers differential expression analyses for RNA-sequencing and microarray studies (2015)

limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.