gebhart/patrepeval huggingface dataset:
Mammalian genes induce partially reprogrammed pluripotent stem cells in non-mammalian vertebrate and invertebrate species (2013)

Cells are fundamental units of life, but little is known about evolution of cell states. Induced pluripotent stem cells (iPSCs) are once differentiated cells that have been re-programmed to an embryonic stem cell-like state, providing a powerful platform for biology and medicine. However, they have been limited to a few mammalian species. Here we found that a set of four mammalian transcription factor genes used to generate iPSCs in mouse and humans can induce a partially reprogrammed pluripotent stem cell (PRPSCs) state in vertebrate and invertebrate model organisms, in mammals, birds, fish, and fly, which span 550 million years from a common ancestor. These findings are one of the first to show cross-lineage stem cell-like induction, and to generate pluripotent-like cells for several of these species with in vivo chimeras. We suggest that the stem-cell state may be highly conserved across a wide phylogenetic range. DOI:http://dx.doi.org/10.7554/eLife.00036.001.
A human-mouse chimeric immunoglobulin gene with a human variable region is expressed in mouse myeloma cells. (1985)

We have constructed and obtained expression of a chimeric human-mouse immunoglobulin gene after transfection into mouse myeloma cells. A human VDJH gene segment was joined to a mouse C kappa gene in the plasmid vector pSV2-gpt, and the construct was transfected into J558L cells by protoplast fusion. Analyses of six transformants by RIA and SDS-PAGE indicated that the chimeric protein was synthesized in large amounts in five. A kappa-specific transcript was observed by Northern blot analysis. Four out of five clones were stable producers of this chimeric chain over a period of 10 mo.
Atmospheric pressure ionization (API) mass spectrometry. Formation of phenoxide ions from chlorinated aromatic compounds (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAtmospheric pressure ionization (API) mass spectrometry. Formation of phenoxide ions from chlorinated aromatic compoundsIsmet. Dzidic, D. I. Carroll, R. N. Stillwell, and E. C. HorningCite this: Anal. Chem. 1975, 47, 8, 1308–1312Publication Date (Print):July 1, 1975Publication History Published online1 May 2002Published inissue 1 July 1975https://pubs.acs.org/doi/10.1021/ac60358a077https://doi.org/10.1021/ac60358a077research-articleACS PublicationsRequest reuse permissionsArticle Views475Altmetric-Citations102LEARN 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
Expression of HERV-K Correlates With Status of MEK–ERK and p16INK4A–CDK4 Pathways in Melanoma Cells (2010)

The dysregulated ERK and RB pathways often coexist in melanoma cells. The K-type human endogenous retrovirus (HERV-K) is implicated in melanomagenesis. Some of the phenotypes that are modified by HERV-K (e.g., changes in cell shape, melanin production, and anchorage-dependent growth) overlap with those that are regulated by ERK and RB pathways. As ERK signaling can regulate retroviruses, we hypothesized that HERV-K expression is controlled by ERK–RB pathways. We found that the levels of HERV-K GAG and EVE correlated with the activation of ERK and loss of p16INK4A and that inhibition of MEK or CDK4, especially in combination, reduced HERV-K EVE in melanoma cells.
Validation of a [3H]Astemizole Binding Assay in HEK293 Cells Expressing HERG K+ Channels (2004)

A radioligand binding assay for the HERG (human ether-a-go-go-related gene) K(+) channel was developed to identify compounds which may have inhibitory activity and potential cardiotoxicity. Pharmacological characterization of the [(3)H]astemizole binding assay for HERG K(+) channels was performed using HERG-expressing HEK293 cells. The assay conditions employed yielded 90% specific binding using 10 microg/well of membrane protein with 1.5 nM of [(3)H]astemizole at 25 degrees C. The K(d) and B(max) values were 5.91 +/- 0.81 nM and 6.36 +/- 0.26 pmol/mg, respectively. The intraassay and interassay variations were 11.4% and 14.9%, respectively. Binding affinities for 32 reference compounds (including dofetilide, cisapride, and terfenadine) with diverse structures demonstrated a similar potency rank order for HERG inhibition to that reported in the literature. Moreover, the [(3)H]astemizole binding data demonstrated a rank order of affinity that was highly correlated to that of inhibitory potency in the electrophysiological studies for HERG in HEK293 (r(SP) = 0.91, P<0.05). In conclusion, the [(3)H]astemizole binding assay is rapid and capable of detecting HERG inhibitors.
The Dibenzocycloheptylamine Alkaloids (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Dibenzocycloheptylamine AlkaloidsEmilia Tojo, Musa H. Abu Zarga, Alan J. Freyer, and Maurice ShammaCite this: J. Nat. Prod. 1989, 52, 5, 1163–1166Publication Date (Print):September 1, 1989Publication History Published online1 July 2004Published inissue 1 September 1989https://pubs.acs.org/doi/10.1021/np50065a044https://doi.org/10.1021/np50065a044research-articleACS PublicationsRequest reuse permissionsArticle Views108Altmetric-Citations7LEARN 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
HYDROXY FATTY ACID GLYCOSIDES OF SOPHOROSE FROM TORULOPSIS MAGNOLIAE (1961)

The oil formed during fermentation by a strain of Torulopsismagnoliae consisted mainly of partly acetylated 2-O-β-D-glucopyranosyl-D-glucopyranose units attached β-glycosidically to 17-L-hydroxyoctadecanoic and 17-L-hydroxy-9-octadecenoic acids.
p56lck-independent activation and tyrosine phosphorylation of p72syk by T-cell antigen receptor/CD3 stimulation. (1994)

Activation of resting T lymphocytes by ligands to the T-cell antigen receptor (TCR)/CD3 complex is initiated by rapid tyrosine phosphorylation of cellular proteins. Protein-tyrosine kinases (PTKs) of the src family are known to be important, but the mechanism of their recruitment and their interactions with PTKs of other families are incompletely understood. We show that a member of another family of PTKs, the p72syk kinase, is constitutively bound to the TCR/CD3 complex and becomes tyrosine phosphorylated and activated within 1 min after TCR/CD3 stimulation. This activation did not depend on the presence of p56lck in T cells and in transfected COS cells. In both cases, however, the phosphorylation of cellular substrates was augmented by src family PTKs. We propose that p72syk may act as an immediate receptor-activated kinase upstream of the related p70zap PTK and the src family PTKs p56lck and p59fyn in T cells and that these src family PTKs act as signal amplifiers.
Oral administration of tylosin phosphate for treatment and prevention of proliferative enteropathy in pigs (1997)

Tylosin phosphate can be effective for prevention and for treatment of PE, using reported dosing schedules. We can experimentally induce PE, using the pure culture challenge-exposure model, for use in testing of treatments.
Molecular Biology of the 3β-Hydroxysteroid Dehydrogenase/Δ5-Δ4 Isomerase Gene Family (2005)

The 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta-HSD) isoenzymes are responsible for the oxidation and isomerization of Delta(5)-3beta-hydroxysteroid precursors into Delta(4)-ketosteroids, thus catalyzing an essential step in the formation of all classes of active steroid hormones. In humans, expression of the type I isoenzyme accounts for the 3beta-HSD activity found in placenta and peripheral tissues, whereas the type II 3beta-HSD isoenzyme is predominantly expressed in the adrenal gland, ovary, and testis, and its deficiency is responsible for a rare form of congenital adrenal hyperplasia. Phylogeny analyses of the 3beta-HSD gene family strongly suggest that the need for different 3beta-HSD genes occurred very late in mammals, with subsequent evolution in a similar manner in other lineages. Therefore, to a large extent, the 3beta-HSD gene family should have evolved to facilitate differential patterns of tissue- and cell-specific expression and regulation involving multiple signal transduction pathways, which are activated by several growth factors, steroids, and cytokines. Recent studies indicate that HSD3B2 gene regulation involves the orphan nuclear receptors steroidogenic factor-1 and dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1 (DAX-1). Other findings suggest a potential regulatory role for STAT5 and STAT6 in transcriptional activation of HSD3B2 promoter. It was shown that epidermal growth factor (EGF) requires intact STAT5; on the other hand IL-4 induces HSD3B1 gene expression, along with IL-13, through STAT 6 activation. However, evidence suggests that multiple signal transduction pathways are involved in IL-4 mediated HSD3B1 gene expression. Indeed, a better understanding of the transcriptional factors responsible for the fine control of 3beta-HSD gene expression may provide insight into mechanisms involved in the functional cooperation between STATs and nuclear receptors as well as their potential interaction with other signaling transduction pathways such as GATA proteins. Finally, the elucidation of the molecular basis of 3beta-HSD deficiency has highlighted the fact that mutations in the HSD3B2 gene can result in a wide spectrum of molecular repercussions, which are associated with the different phenotypic manifestations of classical 3beta-HSD deficiency and also provide valuable information concerning the structure-function relationships of the 3beta-HSD superfamily. Furthermore, several recent studies using type I and type II purified enzymes have elegantly further characterized structure-function relationships responsible for kinetic differences and coenzyme specificity.
Terrain-adaptive locomotion skills using deep reinforcement learning (2016)

Reinforcement learning offers a promising methodology for developing skills for simulated characters, but typically requires working with sparse hand-crafted features. Building on recent progress in deep reinforcement learning (DeepRL), we introduce a mixture of actor-critic experts (MACE) approach that learns terrain-adaptive dynamic locomotion skills using high-dimensional state and terrain descriptions as input, and parameterized leaps or steps as output actions. MACE learns more quickly than a single actor-critic approach and results in actor-critic experts that exhibit specialization. Additional elements of our solution that contribute towards efficient learning include Boltzmann exploration and the use of initial actor biases to encourage specialization. Results are demonstrated for multiple planar characters and terrain classes.
Cutaneous Lupus Erythematosus Associated With Melanoma and BCG Vaccine Therapy (1979)

Abnormalities in host immunologic defenses may be associated with melanoma and lupus erythematosus, In two patients, cutaneous lupus erythematosus developed in the course of melanoma. Immunoglobulin deposits and complement were seen on direct immunofluorescence of exposed uninvolved skin. One patient was undergoing immunotherapy with BCG vaccine when the eruption occurred.
STRUCTURAL AND GENETIC ANALYSIS OF PROTEIN STABILITY (1993)

One very encouraging development has been the freedom with which amino acid replacements can be introduced in a protein of interest. This has made it possible to obtain detailed structural and thermodynamic data on a wide variety of mutants that modify protein stability. Substitutions of solvent-exposed amino acids on the surfaces of proteins are seen to have little if any effect on protein stability or structure, leading to the view that it is the rigid parts of proteins that are critical for folding and stability. There is every reason to expect that it will be possible to rationalize the stabilities of mutant proteins from accurate knowledge of their structures. Substantial progress is being made in quantitating the interactions that determine and stabilize protein structures. Although not specifically the subject of this review, substantial progress is also being made in developing methods to engineer proteins of enhanced stability.
Perceptions of Web site design characteristics: a Malaysian/Australian comparison (2000)

Compares the perceptions of Malaysians (representing eastern, Asian culture) and Australians (representing western, European culture) for four Web site design characteristics – atmospherics, news stories, signs and products and services – as part of the integrated Internet marketing model. Under controlled laboratory conditions, two groupings of 30 subjects evaluated eight Web sites – four in Malaysia and four in Australia – in the retail and services sectors. Hypothesises that the predominant culture is not generalised to another culture. Some tentative support for the research premise is found since where a group’s perceptions for Web design characteristics and their effectiveness was significantly higher, it was for sites originating in that group’s country. Furthermore, perceptions both support and contradict previous research suggesting that Australians prefer an environment of low context and high explicit communications while Asians operate in an environment of high context that stresses implicit communications.
Level of detail management (1998)

Because the human eye perceives less detail at the edges of its field of view, many have proposed that level of detail might be managed by degrading detail at display peripheries. We describe the first systematic examination of the impact of this technique on user performance in a virtual environment. We find that many displays, including those used in this research, have such limited resolution that imperceptible reductions of peripheral detail are impossible. Significant reductions of peripheral detail irrelevant to the task being performed are possible when imperceptible detail reduction is impossible or insufficient. Irrelevant detail reduction can be performed without eye tracking (head tracking only) when 30 horizontal and vertical degrees of visual angle of central detail are preserved. Irrelevant peripheral detail for search, a basic task used in almost all higher level tasks, can be described as that detail necessary for discriminating candidate objects from background with the facility provided by full detail. In order to maintain discriminability throughout the periphery, less reduction of irrelevant peripheral detail should be used at the edges of the field of view.
Little is known about the impact of display speed on usability. Display speed is characterized not only by frame rate and system latency, but also system responsiveness, a time to feedback measure. Frame rate, system latency, and system responsiveness must all be measured before effective management of detail can be exercised. The importance of display speed for usability increases as these four task properties increase: frequency of user input, dependency of user input on displayed information, the amount of display feedback needed during task performance, and the difficulty of the task. Mean display speed should increase and variation in display speed should decrease as the importance of display speed for task performance increases. Detail management strategy should vary as the basic task being performed in an application changes. Control of display speed variation may be quite loose. Drops in speed harm usability more than improvements. Variation reduces usability more when means are already low. Perceivable patterns of variation can harm usability.
Differential Immunogenicity of HIV‐1 Clade C Proteins in Eliciting CD8+and CD4+Cell Responses (2005)

Gag-specific responses dominate the CD4+ T cell response to HIV, whereas CD8+ T cell responses are broadly distributed, which indicates differential immunogenicity of these cells against HIV-1. The preferential targeting of Gag by CD8+ T cells is associated with enhanced control of viral load.
Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection (2014)

Recurrent Clostridium difficile infection (CDI) can be effectively treated by infusion of a healthy donor faeces suspension. However, it is unclear what factors determine treatment efficacy. By using a phylogenetic microarray platform, we assessed composition, diversity and dynamics of faecal microbiota before, after and during follow-up of the transplantation from a healthy donor to different patients, to elucidate the mechanism of action of faecal infusion. Global composition and network analysis of the microbiota was performed in faecal samples from nine patients with recurrent CDI. Analyses were performed before and after duodenal donor faeces infusion, and during a follow-up of 10 weeks. The microbiota data were compared with that of the healthy donors. All patients successfully recovered. Their intestinal microbiota changed from a low-diversity diseased state, dominated by Proteobacteria and Bacilli, to a more diverse ecosystem resembling that of healthy donors, dominated by Bacteroidetes and Clostridium groups, including butyrate-producing bacteria. We identified specific multi-species networks and signature microbial groups that were either depleted or restored as a result of the treatment. The changes persisted over time. Comprehensive and deep analyses of the microbiota of patients before and after treatment exposed a therapeutic reset from a diseased state towards a healthy profile. The identification of microbial groups that constitute a niche for C. difficile overgrowth, as well as those driving the reinstallation of a healthy intestinal microbiota, could contribute to the development of biomarkers predicting recurrence and treatment outcome, identifying an optimal microbiota composition that could lead to targeted treatment strategies.
Identification of Key Charged Residues of Human Interleukin-5 in Receptor Binding and Cellular Activation (1995)

Interleukin-5 (IL-5) is a cytokine that plays a major role in the differentiation and activation of eosinophils. In order to identify which charged residues of human IL-5 are important in binding to its receptor and subsequent cellular activation, we have systematically replaced all of the clusters of charged amino acids with alanine residues. The mutants have been expressed in Escherichia coli, renatured, and purified. They were assayed for ability to cause proliferation of the erythroleukaemic cell line TF-1 and the up-regulation of eosinophil adhesion to ICAM-1. In addition, we studied receptor binding using either immobilized recombinant IL-5 receptor alpha-chain or the alpha/beta-receptor complex expressed on TF-1 cells. The key charged residue involved in binding to the beta-chain of the receptor is Glu-12. This residue is in an identical position to those previously identified in IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) involved in binding to the receptor beta-chain. The alpha-chain binding site is shown to involve the side chains Arg-90 and Glu-109, located in the second beta sheet and after the end of the fourth helix, respectively. It is unique to IL-5 and does not occur in IL-3 or GM-CSF. Understanding the topology of the interaction of IL-5 with its receptor chains will help in the search for rationally designed antagonists of IL-5 function.
Recent developments in the treatment of alcoholic hepatitis (2003)

Alcoholic hepatitis is a form of acute injury to liver tissue that is also a precursor of cirrhosis, and carries significant morbidity and mortality. Severe alcoholic hepatitis in particular carries a high short-term mortality, and also places an enormous burden on stretched healthcare resources. Treatment of alcoholic hepatitis has been limited to supportive management and nutritional supplementation without clear improvements in outcome, and the timing and patient selection for hepatic transplantation is problematic. The use of corticosteroids has remained controversial for many years, but probably has a role in selected patients. Various other therapeutic strategies have been tested over the decades and none has shown any consistent benefit. Recently there have been major developments in our understanding of the mechanisms of alcoholic liver injury, including the role of cytokines and hepatocyte apoptosis. For the first time, there are exciting possibilities for specific therapies for this challenging and serious condition.
A substrate-dependent biological containment system for Pseudomonas putida based on the Escherichia coli gef gene (1993)

A model substrate-dependent suicide system to biologically contain Pseudomonas putida KT2440 is reported. The system consists of two elements. One element carries a fusion between a synthetic lac promoter (PA1-04/03) and the gef gene, which encodes a killing function. This element is contained within a transposaseless mini-Tn5 transposon so that it can be integrated at random locations on the Pseudomonas chromosome. The second element, harbored by plasmid pCC102, is designed to control the first and bears a fusion between the promoter of the P. putida TOL plasmid-encoded meta-cleavage pathway operon (Pm) and the lacI gene, encoding the Lac repressor, plus xylS2, coding for a positive regulator of Pm. In liquid culture under optimal growth conditions and in sterile and nonsterile soil microcosms, P. putida KT2440 (pWWO) bearing the containment system behaves as designed. In the presence of a XylS effector, such as m-methylbenzoate, the LacI protein is synthesized, preventing the expression of the killing function. In the absence of effectors, expression of the PA1-04/03::gef cassette is no longer prevented and a high rate of cell killing is observed. Fluctuation test analyses revealed that mutants resistant to cell killing arise at a frequency of around 10(-5) to 10(-6) per cell per generation. Mutations are linked to the killing element rather than to the regulatory one. In bacteria bearing two copies of the killing cassette, the rate of appearance of mutants resistant to killing decreased to as low as 10(-8) per cell per generation.