gebhart/patrepeval huggingface dataset:
Chemical approaches to targeted protein degradation through modulation of the ubiquitin–proteasome pathway (2017)

Manipulation of the ubiquitin-proteasome system to achieve targeted degradation of proteins within cells using chemical tools and drugs has the potential to transform pharmacological and therapeutic approaches in cancer and other diseases. An increased understanding of the molecular mechanism of thalidomide and its analogues following their clinical use has unlocked small-molecule modulation of the substrate specificity of the E3 ligase cereblon (CRBN), which in turn has resulted in the advancement of new immunomodulatory drugs (IMiDs) into the clinic. The degradation of multiple context-specific proteins by these pleiotropic small molecules provides a means to uncover new cell biology and to generate future drug molecules against currently undruggable targets. In parallel, the development of larger bifunctional molecules that bring together highly specific protein targets in complexes with CRBN, von Hippel-Lindau, or other E3 ligases to promote ubiquitin-dependent degradation has progressed to generate selective chemical compounds with potent effects in cells and <i>in vivo</i> models, providing valuable tools for biological target validation and with future potential for therapeutic use. In this review, we survey recent breakthroughs achieved in these two complementary methods and the discovery of new modes of direct and indirect engagement of target proteins with the proteasome. We discuss the experimental characterisation that validates the use of molecules that promote protein degradation as chemical tools, the preclinical and clinical examples disclosed to date, and the future prospects for this exciting area of chemical biology.
Mixed signals in heart failure: cancer rules (2002)

Pathways for surrogate failing heart phenotypesChamber dilation: diverse cytoskeletal pathways.Changes in organ size, shape, and histological phenotype are central features of both tumorigenesis and heart failure.Chronic increases
Direct Intramuscular Injection of Plasmid DNA Encoding Angiopoietin-1 but not Angiopoietin-2 Augments Revascularization in the Rabbit Ischemic Hindlimb (1998)

Ang1 but not Ang2 gene transfer produces anatomic and physiological evidence of enhanced collateral vessel formation. Ang1 may modulate neovascularization in adult animals and thus represents a feasible therapeutic strategy for patients with tissue ischemia. The role of Ang2 in postnatal neovascularization remains to be clarified.
Distinct Roles of Estrogen Receptors α and β Mediating Acute Vasodilation of Epicardial Coronary Arteries (2007)

This study investigated the contribution of estrogen receptors (ERs) alpha and beta for epicardial coronary artery function, vascular NO bioactivity, and superoxide (O(2)(-)) formation. Porcine coronary rings were suspended in organ chambers and precontracted with prostaglandin F(2alpha) to determine direct effects of the selective ER agonists 4,4',4''-(4-propyl-[(1)H]pyrazole-1,3,5-triyl)tris-phenol (PPT) or 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) or the nonselective ER agonist 17beta-estradiol. Indirect effects on contractility to U46619 and relaxation to bradykinin were assessed and effects on NO, nitrite, and O(2)(-) formation were measured in cultured cells. Within 5 minutes, selective ERalpha activation by PPT, but not 17beta-estradiol or the ERbeta agonist DPN, caused rapid, NO-dependent, and endothelium-dependent relaxation (49+/-5%; P<0.001 versus ethanol). PPT also caused sustained endothelium- and NO-independent vasodilation similar to 17beta-estradiol after 60 minutes (72+/-3%; P<0.001 versus ethanol). DPN induced endothelium-dependent NO-independent relaxation via endothelium-dependent hyperpolarization (40+/-4%; P<0.01 versus ethanol). 17beta-Estradiol and PPT, but not DPN, attenuated the responses to U46619 and bradykinin. All of the ER agonists increased NO and nitrite formation in vascular endothelial but not smooth muscle cells and attenuated vascular smooth muscle cell O(2)(-) formation (P<0.001). ERalpha activation had the most potent effects on both nitrite formation and inhibiting O(2)(-) (P<0.05). These data demonstrate novel and differential mechanisms by which ERalpha and ERbeta activation control coronary artery vasoreactivity in males and females and regulate vascular NO and O(2)(-) formation. The findings indicate that coronary vascular effects of sex hormones differ with regard to affinity to ERalpha and ERbeta, which will contribute to beneficial and adverse effects of hormone replacement therapy.
Spectrum of hemojuvelin gene mutations in 1q-linked juvenile hemochromatosis (2004)

Juvenile or type 2 hemochromatosis (JH) is transmitted as a recessive trait that leads to severe iron overload and organ damage typically before age 30 years. Linkage to a locus on chromosome 1q has been found in most patients with JH. The recently identified causal gene encodes hemojuvelin, a protein with a proposed crucial role in iron metabolism. A second, rare type of JH, with clinical expression identical to the 1q-linked form, is due to inactivation of hepcidin, the key regulator of iron homeostasis. Here we report the spectrum of mutations of the hemojuvelin gene (HJV) in 34 patients who did not show hepcidin mutations. This represents the largest cohort of patients with JH collected worldwide. We identified 17 different (16 novel) mutations of HJV, both at the homozygous and at the compound heterozygous state. Mutations either generate premature termination codons or were missense substitutions, affecting highly conserved residues, relevant to the protein structure and/or function.
OFDM codes for peak-to-average power reduction and error correction (2002)

Orthogonal frequency division multiplexing (OFDM) is a promising way to provide large data rates at reasonable complexity in wireless fading channels. However, a major disadvantage of OFDM is its large peak-to-average power ratio, which significantly decreases the efficiency of the transmitter power amplifier and hence forms a major obstacle to implementing OFDM in portable communication systems. This paper shows the possibility of using complementary codes for both decreasing the peak-to-average power (PAP) ratio and error correction. Set sizes and minimum distance properties of these codes are derived. It is shown that specific subsets of complementary codes have a minimum distance of up to half the code length, while their PAP ratio is only 3 dB. Simulation results demonstrate the viability of using these codes in multipath fading channels. It is currently planned to implement OFDM with complementary codes in the Wireless ATM Network Demonstrator (WAND), a joint European ACTS program.
Cyanuric Chloride Derivatives. I. Aminochloro-s-triazines (1951)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyanuric Chloride Derivatives. I. Aminochloro-s-triazinesJack T. Thurston, James R. Dudley, Donald W. Kaiser, Ingenuin Hechenbleikner, Frederic C. Schaefer, and Dagfrid Holm-HansenCite this: J. Am. Chem. Soc. 1951, 73, 7, 2981–2983Publication Date (Print):July 1, 1951Publication History Published online1 May 2002Published inissue 1 July 1951https://pubs.acs.org/doi/10.1021/ja01151a001https://doi.org/10.1021/ja01151a001research-articleACS PublicationsRequest reuse permissionsArticle Views2838Altmetric-Citations240LEARN 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
Purifications and Characterizations of a Ferredoxin and Its Related 2-Oxoacid:Ferredoxin Oxidoreductase from the Hyperthermophilic Archaeon, Sulfolobus solfataricus P1 (2006)

The coenzyme A-acylating 2-oxoacid:ferredoxin oxidoreductase and ferredoxin (an effective electron acceptor) were purified from the hyperthermophilic archaeon, Sulfolobus solfataricus P1 (DSM1616). The purified ferredoxin is a monomeric protein with an apparent molecular mass of approximately 11 kDa by SDS-PAGE and of 11,180+/-50 Da by MALDI-TOF mass spectrometry. Ferredoxin was identified to be a dicluster, [3Fe-4S][4Fe-4S], type ferredoxin by spectrophotometric and EPR studies, and appeared to be zinc-containing based on the shared homology of its N-terminal sequence with those of known zinc-containing ferredoxins. On the other hand, the purified 2-oxoacid: ferredoxin oxidoreductase was found to be a heterodimeric enzyme consisting of 69 kDa alpha and 34 kDa beta subunits by SDS-PAGE and MALDI-TOF mass spectrometry. The purified enzyme showed a specific activity of 52.6 units/mg for the reduction of cytochrome c with 2-oxoglutarate as substrate at 55 degrees C, pH 7.0. Maximum activity was observed at 70 degrees C and the optimum pH for enzymatic activity was 7.0 -8.0. The enzyme displays broad substrate specificity toward 2-oxoacids, such as pyruvate, 2-oxobutyrate, and 2-oxoglutarate. Among the 2-oxoacids tested (pyruvate, 2-oxobutyrate, and 2-oxoglutarate), 2-oxoglutarate was found to be the best substrate with Km and kcat values of 163 microM and 452 min(-1), respectively. These results provide useful information for structural studies on these two proteins and for studies on the mechanism of electron transfer between the two.
Developmental Expression of Pulmonary Surfactant Protein D (SP-D) (1991)

Surfactant protein D (SP-D) is a collagenous, surfactant-associated, carbohydrate-binding protein that is synthesized by pulmonary epithelial cells. In the present studies, we examined the expression of SP-D and SP-D mRNA during late fetal (day 17, 19, 21) and early postnatal (day 5) rat lung development using immunochemical, cell-free translation, and Northern hybridization assays. SP-D mRNA and immunoreactive SP-D protein were first detected in guanidine extracts of whole rat lung at 21 days of gestation and reached even higher concentrations during the postnatal period. Likewise, immunoperoxidase studies of rat lung using affinity-purified antibodies to SP-D showed no staining at day 17 or 19, but demonstrated strong cytoplasmic staining of cuboidal epithelial cells lining immature airspaces at day 21 and strong cytoplasmic staining of type II and nonciliated bronchiolar cells in adult lung. SP-D also appeared in amniotic fluid by day 21 and was partially purified by affinity chromatography on maltosyl-agarose under conditions used for the isolation of rat lung SP-D. These studies indicate that the production of SP-D is increased shortly prior to birth, and that the increases in total lung SP-D and SP-D mRNA are temporally correlated with SP-D secretion and the appearance of SP-D in amniotic fluid.
Complete discrete 2-D Gabor transforms by neural networks for image analysis and compression (1988)

A three-layered neural network is described for transforming two-dimensional discrete signals into generalized nonorthogonal 2-D Gabor representations for image analysis, segmentation, and compression. These transforms are conjoint spatial/spectral representations, which provide a complete image description in terms of locally windowed 2-D spectral coordinates embedded within global 2-D spatial coordinates. In the present neural network approach, based on interlaminar interactions involving two layers with fixed weights and one layer with adjustable weights, the network finds coefficients for complete conjoint 2-D Gabor transforms without restrictive conditions. In wavelet expansions based on a biologically inspired log-polar ensemble of dilations, rotations, and translations of a single underlying 2-D Gabor wavelet template, image compression is illustrated with ratios up to 20:1. Also demonstrated is image segmentation based on the clustering of coefficients in the complete 2-D Gabor transform.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Simian Immunodeficiency Viruses (1990)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Automated quantification in tissue Doppler imaging (2002)

Tissue Doppler mapping is an emerging Color Doppler imaging technology, which measures and displays the velocity of moving tissue such as the myocardium. Several clinical studies have shown that the ability to accurately measure myocardial velocity may prove a valuable diagnostic tool in characterizing regional heart function. To address these measurement needs, a quantification technique has been developed which combines grayscale edge detection with Doppler tracking to automatically trace the myocardial structures of interest on the M-mode image throughout the cardiac cycle. These traces are then used to obtain accurate velocity waveforms such as the mean velocity and velocity gradient waveforms within the myocardium. This paper provides an algorithmic description of the automated quantification technique, and presents an overview of some of the clinical results obtained so far.
The Volterra and Wiener Theories of Nonlinear Systems (1980)

This text presents a complete and detailed development of the analysis, design and characterization of non-linear systems using the Volterra and Wiener theories, as well as gate functions, thus yielding new insights and a better comprehension of the subject. The Volterra and Wiener theories are useful in the study of systems in biological, mechanical, and electrical fields.
Transcriptional Regulation of the AP-2α Promoter by BTEB-1 and AP-2rep, a Novel wt-1/egr-Related Zinc Finger Repressor (1999)

AP-2 transcription factors have been suggested to exert key regulatory functions in vertebrate embryonic development, in tumorigenicity of various cancer cell types, and in controlling cell cycle and apoptotic effector genes. In this study, we investigated transcriptional regulation of the AP-2alpha gene promoter mediated by an autoregulatory element (referred to as A32) with a core consensus AP-2 binding site at position -336 relative to the mRNA initiation site. AP-2 and multiple different nuclear proteins in HeLa and Neuro2A cell extracts form specific bandshifts with the A32 element. By screening a mouse brain cDNA expression library, we isolated two different cDNAs encoding the transcription factor BTEB-1 and a novel zinc finger protein, AP-2rep. AP-2rep reveals a modular structure with homology to transcription factors of the wt-1/egr-1-family. AP-2rep, BTEB-1, and AP-2 interact in a mutually exclusive manner with overlapping binding sites in the A32 element. Transfection studies revealed that BTEB-1 is a strong activator of AP-2alpha promoter activity, whereas cotransfected AP-2alpha resulted in moderate autoactivation of promoter activity. In contrast, AP-2rep confers strong transcriptional repression to the AP-2alpha gene, and we observed an excellent correlation between induction of AP-2rep mRNA expression and downregulation of AP-2alpha mRNA during development of the kidney. In summary, we have identified multiple transcription factors and cloned from an expression library a novel zinc finger silencing factor, AP-2rep, mediating positive and negative regulation of AP-2alpha expression through a set of overlapping cis-regulatory promoter elements.
Derivatives of Aminomethanethiol (1939)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDerivatives of AminomethanethiolArthur. Binz and Leland H. PenceCite this: J. Am. Chem. Soc. 1939, 61, 11, 3134–3139Publication Date (Print):November 1, 1939Publication History Published online1 May 2002Published inissue 1 November 1939https://pubs.acs.org/doi/10.1021/ja01266a046https://doi.org/10.1021/ja01266a046research-articleACS PublicationsRequest reuse permissionsArticle Views216Altmetric-Citations9LEARN 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
A butterfly subdivision scheme for surface interpolation with tension control (1990)

A new interpolatory subdivision scheme for surface design is presented. The new scheme is designed for a general triangulation of control points and has a tension parameter that provides design flexibility. The resulting limit surface is C 1 for a specified range of the tension parameter, with a few exceptions. Application of the butterfly scheme and the role of the tension parameter are demonstrated by several examples.
Chronic Hypoxia Impairs Muscle Function in the Drosophila Model of Duchenne's Muscular Dystrophy (DMD) (2010)

Duchenne's muscular dystrophy (DMD) is a severe progressive myopathy caused by mutations in the DMD gene leading to a deficiency of the dystrophin protein. Due to ongoing muscle necrosis in respiratory muscles late-stage DMD is associated with respiratory insufficiency and chronic hypoxia (CH). To understand the effects of CH on dystrophin-deficient muscle in vivo, we exposed the Drosophila model for DMD (dmDys) to CH during a 16-day ascent to the summit of Mount Denali/McKinley (6194 meters above sea level). Additionally, dmDys and wild type (WT) flies were also exposed to CH in laboratory simulations of high altitude hypoxia. Expression profiling was performed using Affymetrix GeneChips® and validated using qPCR. Hypoxic dmDys differentially expressed 1281 genes, whereas the hypoxic WT flies differentially expressed 56 genes. Interestingly, a number of genes (e.g. heat shock proteins) were discordantly regulated in response to CH between dmDys and WT. We tested the possibility that the disparate molecular responses of dystrophin-deficient tissues to CH could adversely affect muscle by performing functional assays in vivo. Normoxic and CH WT and dmDys flies were challenged with acute hypoxia and time-to-recover determined as well as subjected to climbing tests. Impaired performance was noted for CH-dmDys compared to normoxic dmDys or WT flies (rank order: Normoxic-WT ≈ CH-WT> Normoxic-dmDys> CH-dmDys). These data suggest that dystrophin-deficiency is associated with a disparate, pathological hypoxic stress response(s) and is more sensitive to hypoxia induced muscle dysfunction in vivo. We hypothesize that targeting/correcting the disparate molecular response(s) to hypoxia may offer a novel therapeutic strategy in DMD.
Fontenay au-delà de saint Bernard. À propos de deux publications récentes sur l’abbaye et son architecture (2003)

status: Published
A stereospeifically18O-labelled deoxydinucleoside phosphate block for incorporation into an oligonucleotide (1983)

Fully protected diastereoisomers of deoxyguanylyl (3' leads to 5') deoxyadenosine stereospecifically labelled on phosphorus with oxygen-18 have been synthesized by oxidation of phosphite triester intermediates in the presence of 18O-labelled water. The diastereoisomers have been chromatographically separated and their absolute configuration at phosphorus determined. (Rp)-[18O]deoxyguanylyl (3' leads to 5')deoxyadenosine has been prepared by complete deprotection of the parent diastereoisomer of the Sp configuration. Methylation of the former compound permits assignment of the absolute configurations of the methyl esters of N1-methyldeoxyguanylyl (3' leads to 5') N1-methyldeoxyadenosine.
Caspase-9 Can Be Activated without Proteolytic Processing (1999)

The recombinant form of the proapoptotic caspase-9 purified following expression in Escherichia coli is processed at Asp315, but largely inactive; however, when added to cytosolic extracts of human 293 cells it is activated 2000-fold in the presence of cytochrome c and dATP. Thus, the characteristic activities of caspase-9 are context-dependent, and its activation may not recapitulate conventional caspase activation mechanisms. To explore this hypothesis we produced recombinant forms of procaspase-9 containing mutations that disabled one or both of the interdomain processing sites of the zymogen. These mutants were able to activate downstream caspases, but only in the presence of cytosolic factors. The mutant with both processing sites abolished had 10% of the activity of wild-type, and was able to support apoptosis, with equal vigor to wild-type, when transiently expressed in 293 cells. Thus caspase-9 has an unusually active zymogen that does not require proteolytic processing, but instead is dependent on cytosolic factors for expression of its activity.
Identification of an Immunoreceptor Tyrosine-Based Activation Motif of K1 Transforming Protein of Kaposi’s Sarcoma-Associated Herpesvirus (1998)

Kaposi's sarcoma-associated herpesvirus (KSHV) is consistently identified in Kaposi's sarcoma and body cavity-based lymphoma. KSHV encodes a transforming protein called K1 which is structurally similar to lymphocyte receptors. We have found that a highly conserved region of the cytoplasmic domain of K1 resembles the sequence of immunoreceptor tyrosine-based activation motifs (ITAMs). To demonstrate the signal-transducing activity of K1, we constructed a chimeric protein in which the cytoplasmic tail of the human CD8alpha polypeptide was replaced with that of KSHV K1. Expression of the CD8-K1 chimera in B cells induced cellular tyrosine phosphorylation and intracellular calcium mobilization upon stimulation with an anti-CD8 antibody. Mutational analyses showed that the putative ITAM of K1 was required for its signal-transducing activity. Furthermore, tyrosine residues of the putative ITAM of K1 were phosphorylated upon stimulation, and this allowed subsequent binding of SH2-containing proteins. These results demonstrate that the KSHV transforming protein K1 contains a functional ITAM in its cytoplasmic domain and that it can transduce signals to induce cellular activation.