gebhart/patrepeval huggingface dataset:
Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells (2000)

Phosphatidylinositol 3-kinase (PI 3-kinase) is a signaling molecule that controls numerous cellular properties and activities. The oncogene v-p3k is a homolog of the gene coding for the catalytic subunit of PI 3-kinase, p110alpha. P3k induces transformation of cells in culture, formation of hemangiosarcomas in young chickens, and myogenic differentiation in myoblasts. Here, we describe a role of PI 3-kinase in angiogenesis. Overexpression of the v-P3k protein or of cellular PI 3-kinase equipped with a myristylation signal, Myr-P3k, can induce angiogenesis in the chorioallantoic membrane (CAM) of the chicken embryo. This process is characterized by extensive sprouting of new blood vessels and enlargement of preexisting vessels. Overexpression of the myristylated form of the PI 3-kinase target Akt, Myr-Akt, also induces angiogenesis. Overexpression of the tumor suppressor PTEN or of dominant-negative constructs of PI 3-kinase inhibits angiogenesis in the yolk sac of chicken embryos, suggesting that PI 3-kinase and Akt signaling is required for normal embryonal angiogenesis. The levels of mRNA for vascular endothelial growth factor (VEGF) are elevated in cells expressing activated PI 3-kinase or Myr-Akt. VEGF mRNA levels are also increased by insulin treatment through the PI 3-kinase-dependent pathway. VEGF mRNA levels are decreased in cells treated with the PI 3-kinase inhibitor LY294002 and restored by overexpression of v-P3k or Myr-Akt. Overexpression of VEGF by the RCAS vector induces angiogenesis in chicken embryos. These results suggest that PI 3-kinase plays an important role in angiogenesis and regulates VEGF expression.
Synthesis of N-Demethyl-N-Substituted-14-Hydroxycodeine and Morphine Derivatives+ (1992)

Abstract A fews representatives (1b-d) of a novel group of structurally related morphine-antagonist compounds have been prepared in stereochemically homogeneous form. The employed procedures involve O-demethylation either of the corresponding codeine derivatives 2b-d, or those of the N-alkylated analogues 2b-c synthesized from N-demethylthebaine (7a) by means of N-alkylation and subsequent transformations of 7b, d–compounds selected from the resulting functionalized thebaines 7b-exs.
Maturation of isoprenylated proteins in Saccharomyces cerevisiae. Multiple activities catalyze the cleavage of the three carboxyl-terminal amino acids from farnesylated substrates in vitro. (1992)

Eukaryotic polypeptides containing COOH-terminal-CXXX sequences can be posttranslationally modified by isoprenylation of the cysteine residue via a thioether linkage, proteolytic removal of the three terminal amino acids, and alpha-carboxyl methylation of the cysteine residue. Through the development of an indirect coupled assay, we have identified three in vitro activities in the yeast Saccharomyces cerevisiae that can catalyze the proteolytic cleavage of the three COOH-terminal amino acids of the synthetic peptide substrate N-acetyl-KSKTK[S-farnesyl-Cys]VIM. One of these is the vacuolar protease carboxypeptidase Y. Using a mutant strain deficient in this enzyme, we find evidence for an additional soluble activity as well as for a membrane-associated activity. These latter activities are candidates for roles in the physiological processing of isoprenylated protein precursors. They are both insensitive to inhibitors of serine and aspartyl proteinases but are sensitive to sulfhydryl reagents and 0.5 mM ZnCl2. The soluble activity appears to be a metalloenzyme, inhibitable by 2 mM o-phenanthroline but not by 1 mM N-ethylmaleimide, whereas the membrane-associated enzyme is inhibitable by 1 mM N-ethylmaleimide but not 2 mM o-phenanthroline. We show that the membrane-bound protease is not an activity of the membrane-bound methyltransferase, because protease activity is observed in membrane preparations that lack the STE14-encoded methyltransferase. The soluble activity appears to be a novel carboxypeptidase of approximately 110 kDa that catalyzes a processive removal of amino acids from the COOH terminus from both the farnesylated and non-farnesylated substrate, but not from three other unrelated peptides. Finally, we find no evidence for non-vacuolar membrane or soluble activities that catalyze the ester hydrolysis of N-acetyl-S-farnesyl-L-cysteine methyl ester.
Kinetic analysis of 18F-fluorodihydrorotenone as a deposited myocardial flow tracer: comparison to 201Tl. (2004)

The superior correlation of (18)F-FDHR uptake with flow indicates that it is a better flow tracer than (201)Tl in the isolated rabbit heart. Compared with the other currently available positron-emitting flow tracers ((82)Rb, (13)N-ammonia, and (15)O-water), (18)F-FDHR has the potential of providing excellent image resolution without the need for an on-site cyclotron.
A first-in-human phase I study to evaluate the pan-PI3K inhibitor GDC-0941 administered QD or BID in patients with advanced solid tumors (2009)

3501 Background: The PI3K-PTEN-AKT signaling pathway is deregulated in a wide variety of cancers. GDC-0941 is a potent and selective oral inhibitor of the class I PI3K with 3 nM IC50 for the p110-alpha subunit in vitro and 28 nM IC50 in a cell-based pAKT assay and demonstrates broad activity in breast, ovarian, lung, and prostate cancer models. Methods: A Phase I dose escalation study using a 3+3 design was initiated in patients (pts) with solid tumors. GDC-0941 was given on d1, followed by 1 wk washout to study single-dose PK and PD markers. GDC-0941 was then administered qd on a 3 wk on, 1 wk off, schedule. Steady-state PK and PD were evaluated after 1 wk of continuous dosing. A separate concurrent dose-escalation arm with bid dosing was initiated after the third qd cohort. Results: Nineteen pts have been enrolled in 5 successive dose-escalation cohorts in the qd arm with dose levels up to 80 mg daily. Seven pts were enrolled in 2 cohorts in the bid arm at total daily doses of 60 and 80 mg. The most frequently reported drug-related AEs were Grade 1/2 nausea, fatigue, diarrhea, peripheral edema, and dysgeusia; no drug related grade &gt;3 events have been reported. PK data suggest dose-proportional increases in Cmax and AUC. Potential signs of anti-tumor activity have been observed with a soft tissue sarcoma pt on-study for &gt;176 days with stable disease (30 mg qd), an ovarian cancer pt with an on-study 2.8-fold decrease in CA-125 response to normal levels (30 mg bid) and a pt with endometrial cancer with a decrease in tumor FDG-PET uptake (80 mg qd). Conclusions: GDC-0941 is generally well-tolerated with potential signs of anti-tumor activity. Preliminary PK data suggest dose-proportional increases in exposure over the dose levels evaluated. Dose-escalation on both the qd and bid schedules continues with updated data to be presented. [Table: see text]
Doubly Stochastic Normalization for Spectral Clustering (2007)

In this paper we focus on the issue of normalization of the affinity matrix in spectral clustering. We show that the difference between N-cuts and Ratio-cuts is in the error measure being used (relative-entropy versus L1 norm) in finding the closest doubly-stochastic matrix to the input affinity matrix. We then develop a scheme for finding the optimal, under Frobenius norm, doubly-stochastic approximation using Von-Neumann's successive projections lemma. The new normalization scheme is simple and efficient and provides superior clustering performance over many of the standardized tests.
Refining, bleaching and hydrogenating meat fats (1985)

Abstract Meat fats are most often steam refined. This has been the accepted practice for at least 35 years. Meat fats are caustic refined for a few specialized products. The caustic refining conditions differ from those used for vegetable oils primarily in the amount of mixing used after the addition of caustic. Bleaching of meat fats is accomplished easily. Most meat fats are light in color and require clarification more than bleaching. The green color of tallows containing large amounts of chlorophyll is easily removed with activated earth. Meat fats are hydrogenated to develop the SFI curves needed for various products and also are hydrogenated to saturation for use as plasticizing agents. The hydrogenation of lard and tallow is not as complicated as that of most vegetable oils, because the original fat is more saturated and the reaction has fewer possible routes to follow.
The Effect of Smoking on the Transcriptional Regulation of Lung Inflammation in Patients with Chronic Obstructive Pulmonary Disease (2006)

These data propose a role for modification of nucleosomal structure in inflammatory cytokine gene transcription in response to smoking. The imbalance between histone deacetylation and acetylation in favor of acetylation may contribute to the enhanced inflammation in smokers susceptible to the development of COPD.
A KNOWLEDGE-BASED ANSWER ENGINE FOR OPEN-DOMAIN QUESTIONS (2001)

This paper describes a knowledge-based methodology of mining textual answers from large collections of texts. We present an answer engine capable of providing answers to any question posed in natural language, regardless of the domain of interest. The answers are produced by combining semantic data from question taxonomies with information abductively inferred from texts. The high precision of the retrieved answers is due to novel, efficient knowledge processing techniques.
Massively parallel sequencing of single cells by epicPCR links functional genes with phylogenetic markers (2015)

Many microbial communities are characterized by high genetic diversity. 16S ribosomal RNA sequencing can determine community members, and metagenomics can determine the functional diversity, but resolving the functional role of individual cells in high throughput remains an unsolved challenge. Here, we describe epicPCR (Emulsion, Paired Isolation and Concatenation PCR), a new technique that links functional genes and phylogenetic markers in uncultured single cells, providing a throughput of hundreds of thousands of cells with costs comparable to one genomic library preparation. We demonstrate the utility of our technique in a natural environment by profiling a sulfate-reducing community in a freshwater lake, revealing both known sulfate reducers and discovering new putative sulfate reducers. Our method is adaptable to any conserved genetic trait and translates genetic associations from diverse microbial samples into a sequencing library that answers targeted ecological questions. Potential applications include identifying functional community members, tracing horizontal gene transfer networks and mapping ecological interactions between microbial cells.
The primary structure of the 3-phosphoglycerate kinase (PGK) gene from Kluyveromyces lactis (1990)

Journal Article The primary structure of the 3-phosphoglycerate kinase (PGK) gene from Kluyveromyces lactis Get access Alain Fournier, Alain Fournier Rhône Poulenc Santé, Biotechnology Department13 Quai Jules Guesde, 94403 Vitry Cedex, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Reinhard Fleer, Reinhard Fleer Rhône Poulenc Santé, Biotechnology Department13 Quai Jules Guesde, 94403 Vitry Cedex, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Patrice Yeh, Patrice Yeh Rhône Poulenc Santé, Biotechnology Department13 Quai Jules Guesde, 94403 Vitry Cedex, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Jean-François Mayaux Jean-François Mayaux Rhône Poulenc Santé, Biotechnology Department13 Quai Jules Guesde, 94403 Vitry Cedex, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 18, Issue 2, 25 January 1990, Page 365, https://doi.org/10.1093/nar/18.2.365 Published: 25 January 1990 Article history Received: 05 December 1989 Published: 25 January 1990
A system for small target detection, tracking, and classification (2003)

A system is developed for small target detection, tracking and classification. The specific application of interest is an automatic headlight dimming system (AutoDim) for automotive night-time driving use. The burden of controlling the state of the vehicle's headlights (high or low beam) is taken away from the driver and shifted on to the AutoDim system. AutoDim's decision as to whether or not to change the state of the headlights is made from visual information obtained from a low-cost, low-resolution CMOS video camera. The targets of potential interest (i.e. light sources) are detected based on their brightness, geometric and spatial attributes. However, this also detects segments that do not correspond to the vehicular tail/headlights. Typical sources of error include street lights, reflected light, sky light, etc. To eliminate such errors, and to discriminate vehicular tail/headlight sources from other light sources, a non-parametric classifier is employed using a feature set that includes the light source's spectral distribution and temporal track record, in addition to the attributes used for detection.
NMR of α‐synuclein–polyamine complexes elucidates the mechanism and kinetics of induced aggregation (2004)

The aggregation of alpha-synuclein is characteristic of Parkinson's disease (PD) and other neurodegenerative synucleinopathies. The 140-aa protein is natively unstructured; thus, ligands binding to the monomeric form are of therapeutic interest. Biogenic polyamines promote the aggregation of alpha-synuclein and may constitute endogenous agents modulating the pathogenesis of PD. We characterized the complexes of natural and synthetic polyamines with alpha-synuclein by NMR and assigned the binding site to C-terminal residues 109-140. Dissociation constants were derived from chemical shift perturbations. Greater polyamine charge (+2 --> +5) correlated with increased affinity and enhancement of fibrillation, for which we propose a simple kinetic mechanism involving a dimeric nucleation center. According to the analysis, polyamines increase the extent of nucleation by approximately 10(4) and the rate of monomer addition approximately 40-fold. Significant secondary structure is not induced in monomeric alpha-synuclein by polyamines at 15 degrees C. Instead, NMR reveals changes in a region (aa 22-93) far removed from the polyamine binding site and presumed to adopt the beta-sheet conformation characteristic of fibrillar alpha-synuclein. We conclude that the C-terminal domain acts as a regulator of alpha-synuclein aggregation.
Molecular Weight Dependence of the Crystallization Kinetics of Linear Polyethylene. I. Experimental Results (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMolecular Weight Dependence of the Crystallization Kinetics of Linear Polyethylene. I. Experimental ResultsE. Ergoz, J. G. Fatou, and L. MandelkernCite this: Macromolecules 1972, 5, 2, 147–157Publication Date (Print):March 1, 1972Publication History Published online1 May 2002Published inissue 1 March 1972https://pubs.acs.org/doi/10.1021/ma60026a011https://doi.org/10.1021/ma60026a011research-articleACS PublicationsRequest reuse permissionsArticle Views1161Altmetric-Citations196LEARN 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
Precision Genome Engineering and Agriculture: Opportunities and Regulatory Challenges (2014)

Plant agriculture is poised at a technological inflection point. Recent advances in genome engineering make it possible to precisely alter DNA sequences in living cells, providing unprecedented control over a plant's genetic material. Potential future crops derived through genome engineering include those that better withstand pests, that have enhanced nutritional value, and that are able to grow on marginal lands. In many instances, crops with such traits will be created by altering only a few nucleotides among the billions that comprise plant genomes. As such, and with the appropriate regulatory structures in place, crops created through genome engineering might prove to be more acceptable to the public than plants that carry foreign DNA in their genomes. Public perception and the performance of the engineered crop varieties will determine the extent to which this powerful technology contributes towards securing the world's food supply.
Treatment of rheumatoid arthritis with methotrexate: a prospective open longterm study of 191 cases. (1991)

One hundred and ninety-one patients with severe rheumatoid arthritis (RA) were included in a prospective open longterm study of the safety, efficacy and maintenance of methotrexate (MTX) treatment. The mean duration of MTX treatment was 19 +/- 13.2 (3-58) months; the mean weekly dose of MTX was 10.2 +/- 0.2 mg. Analysis of the 191 patients in an intent-to-treat manner showed a significant improvement of all the clinical variables and a decrease of erythrocyte sedimentation rate with a steroid sparing effect. The probability of continuing MTX therapy for up to 2 years was 65% and for up to 5 years was 46%. Adverse effects of MTX occurred in 37.1% of the patients, but only 15.7% discontinued MTX permanently.
Atomic mercury vapor inside a hollow-core photonic crystal fiber (2014)

We demonstrate high atomic mercury vapor pressure in a kagomé-style hollow-core photonic crystal fiber at room temperature. After a few days of exposure to mercury vapor the fiber is homogeneously filled and the optical depth achieved remains constant. With incoherent optical pumping from the ground state we achieve an optical depth of 114 at the 6(3)P(2) - 6(3)D(3) transition, corresponding to an atomic mercury number density of 6 × 10(10) cm(-3). The use of mercury vapor in quasi one-dimensional confinement may be advantageous compared to chemically more active alkali vapor, while offering strong optical nonlinearities in the ultraviolet region of the optical spectrum.
Lymphokines and the immune response (1990)

Perspectives on Cell Mediated Immunity In Vivo. The Cytokine Concept: Historical Perspectives and Current Status of the Cloned Cytokines. T Cell Clones as Sources of Lymphokines. Receptors on T and B Lymphocytes. Intracellular and Extracellular Factors Promoting Lymphocyte Activation and Proliferation. Transmembrane Signaling in B Cell Activation. Lymphoid Growth Factors: Gene Regulation and Biochemical Mechanisms of Action. Interleukin 1 and its Biologically Related Cytokines. Interleukin 2. Cachectin (Tumor Necrosis Factor) and Lymphotoxin as Primary Mediators of Tissue Catabolism, Inflammation, and Shock. Production of Hemopoietic Colony Stimulating Factors. Lymphokines and Tumor Immunity. Lymphokines and Cytokines in Reparative Processes.
Optical Power Splitting Techniques Using Photonic Crystal Line Defect Waveguides (2011)

An innocuous sensory event (a prestimulus) briefly preceding a startle-eliciting stimulus (SES) reduces the amplitude of the elicited reflex. This study used signal detection theory (SDT) techniques to quantify the effects of gaps (pauses in otherwise continuous noise) on the rat's acoustic startle reflex. Sixteen rats were given four identical test sessions consisting of the randomized presentation of 150 trials of the SES alone and 150 trials of a gap-and-SES combination. Gap duration (1, 2, 4, and 8 msec) varied between sessions. Data analyses based on amplitude, difference scores, percentage scores, and SDT techniques identified similar patterns. The three longest gaps, but not the shortest, were reliably detected, and differences among these three were identified with percentage and SDT analyses. Analyses of amplitude changes over test sessions yielded different patterns for each measure. The results demonstrate that an SDT analysis is a sensitive index of prestimulus effects.
Adenoviral gene transfer of GDNF, BDNF and TGFβ2, but not CNTF, cardiotrophin‐1 or IGF1, protects injured adult motoneurons after facial nerve avulsion (2003)

We examined neuroprotective effects of recombinant adenoviral vectors encoding glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT1), insulin-like growth factor-1 (IGF1), and transforming growth factor-beta2 (TGFbeta2) on lesioned adult rat facial motoneurons. The right facial nerves of adult Fischer 344 male rats were avulsed and removed from the stylomastoid foramen, and adenoviral vectors were injected into the facial canal. Animals avulsed and treated with adenovirus encoding GDNF, BDNF, CNTF, CT1, IGF1 and TGFbeta2 showed intense immunolabeling for these factors in lesioned facial motoneurons, respectively, indicating adenoviral induction of the neurotrophic factors in these neurons. The treatment with adenovirus encoding GDNF, BDNF, or TGFbeta2 after avulsion significantly prevented the loss of lesioned facial motoneurons, improved choline acetyltransferase immunoreactivity and prevented the induction of nitric oxide synthase activity in these neurons. The treatment with adenovirus encoding CNTF, CT1 or IGF1, however, failed to protect these neurons after avulsion. These results indicate that the gene transfer of GDNF and BDNF and TGFbeta2 but not CNTF, CT1 or IGF1 may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.
Human pancreatic RNase1-human epidermal growth factor fusion: an entirely human 'immunotoxin analog' with cytotoxic properties against squamous cell carcinomas (1998)

The gene encoding human pancreatic ribonuclease 1 (hpRNasel) was fused with a gene encoding human epidermal growth factor (hEGF). The hybrid human protein was isolated from Escherichia coli inclusion bodies, refolded and purified to homogeneity. The fusion protein competed with 125I-hEGF for binding to hEGF receptors (EGFR) and had ribonucleolytic activities approaching those of hpRNase1. Several conformations having different enzymatic activities could be detected after reversed-phase high-performance liquid chromatographic analysis, the less hydrophobic molecules being the most active. The hybrid protein was specifically cytotoxic to A431, an EGFR overexpressing squamous carcinoma cell line, with an IC50 of approximately 10(-7) M. In contrast, recombinant hpRNase1 had an IC50 higher than 10(-4) M. A mixture of free hEGF and free hpRNasel was not more cytotoxic than hpRNasel alone and no cytotoxicity was detected in EGFR-deficient control cells. Taken together, these data suggest that this construct might be useful for targeted therapy of esophageal, lung and other squamous cell carcinomas and also breast cancers overexpressing EGFR, which correlate with a poor prognosis and cannot be cured by surgery alone. Engineering hybrid molecules with endogenous human proteins for targeted therapy may alleviate the dose-limiting immunogenicity and toxicity of conventional immunotoxins.