gebhart/patrepeval huggingface dataset:
A Single Point Mutation in a Group I WW Domain Shifts Its Specificity to That of Group II WW Domains (1999)

WW domains can be divided into three groups based on their binding specificity. By random mutagenesis, we switched the specificity of the Yes-associated protein (YAP) WW1 domain, a Group I WW domain, to that of the FE65 WW domain, which belongs to Group II. We showed that a single mutation, leucine 190 (betaB5) to tryptophan, is required to switch from Group I to Group II. Although this single substitution in YAP WW1 domain is sufficient to precipitate the two protein isoforms of Mena, an in vivo ligand of FE65, we showed that an additional substitution, histidine 192 (betaB7) to glycine, significantly increased the ability of YAP to mimic FE65. This double mutant (L190W/H192G) precipitates eight of the nine protein bands that FE65 pulls down from rat brain protein lysates. Based on both our data and a sequence comparison between Group I and Group II WW domains, we propose that a block of three consecutive aromatic amino acids within the second beta-sheet of the domain is required, but not always sufficient, for a WW domain to belong to Group II. These data deepen our understanding of WW domain binding specificity and provide a basis for the rational design of modified WW domains with potential therapeutic applications.
Skeletal abnormalities in doubly heterozygousBmp4 andBmp7 mice (1998)

Analysis of the skeletal phenotypes caused by the genetic inactivation of individual Bmps, along with the study of their expression patterns, suggest possible functional redundancy of these molecules. To investigate the effect on skeleton development of the combined absence of some Bmp genes expressed in the same areas, we have intercrossed heterozygous Bmp7 mice with Bmp2 +/-, Bmp4 +/-, or Bmp5 +/- animals. Bmp2/7 and Bmp5/7 double heterozygous animals do not present with any abnormalities. In contrast, Bmp4/7 double heterozygotes develop minor defects in two restricted areas of the skeleton, the rib cage, and the distal part of the limbs. In the ribs, Bmp4 and Bmp7 seem to act in the same pathway to assure proper guidance of mesenchymal condensations of the ribs extending toward the sternum. In the limbs, these molecules appear to play a similar role in controlling digit number, possibly through induction of apoptosis in the interdigital and anterior mesenchyme.
A new class of cation conductors: polyphosphazene sulfonates (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA new class of cation conductors: polyphosphazene sulfonatesS. Ganapathiappan, Kaimin Chen, and D. F. ShriverCite this: Macromolecules 1988, 21, 7, 2299–2301Publication Date (Print):July 1, 1988Publication History Published online1 May 2002Published inissue 1 July 1988https://pubs.acs.org/doi/10.1021/ma00185a075https://doi.org/10.1021/ma00185a075research-articleACS PublicationsRequest reuse permissionsArticle Views263Altmetric-Citations46LEARN 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
Glucose-Dependent Insulinotropic Polypeptide Confers Early Phase Insulin Release to Oral Glucose in Rats: Demonstration by a Receptor Antagonist1 (2000)

A novel GIP receptor antagonist was developed to evaluate the acute role of glucose-dependent insulinotropic polypeptide (GIP) in the insulin response to oral glucose in rats. Antisera to an extracellular epitope of the GIP receptor (GIPR) detected immunoreactive GIPR on rat pancreatic beta-cells. Purified GIPR antibody (GIPR Ab) specifically displaced GIP binding to the receptor and blocked GIP-mediated increases in intracellular cAMP. When delivered to rats by ip injection, GIPR Ab had a half-life of approximately 4 days. Treatment with GIPR Ab (1 microg/g BW) blocked the potentiation of glucose-stimulated insulin secretion by GIP (60 pmol) but not glucagon-like peptide-1 (GLP-1, 60 pmol) in anesthetized rats. The insulin response to oral glucose was delayed in conscious unrestrained rats that were pretreated with GIPR Ab. Plasma insulin levels were approximately 35% lower at 10 min in GIPR Ab treated animals compared with controls. As a result, the glucose excursion was greater in the GIPR Ab treated group. Fasting plasma glucose levels were not altered by GIPR Ab. We conclude that release of GIP following oral glucose may act as an anticipatory signal to pancreatic beta-cells to promote rapid release of insulin for glucose disposal.
Measuring clinical enthesitis in psoriatic arthritis: Assessment of existing measures and development of an instrument specific to psoriatic arthritis (2008)

The LEI is a new enthesitis index designed for use in PsA. It shows good test characteristics that suggest it will be a robust and reliable assessment tool. We suggest that it be adopted for use in any randomized controlled trials and longitudinal observation cohorts involving patients with PsA.
Design and Fabrication of a Micromachined Planar Patch-Clamp Substrate With Integrated Microfluidics for Single-Cell Measurements (2006)

We have designed, fabricated, tested, and integrated microfabricated planar patch-clamp substrates and poly(dimethylsiloxane) (PDMS) microfluidic components. Substrates with cell-patch-site aperture diameters ranging from 300nm to 12 /spl mu/m were produced using standard MEMS-fabrication techniques. The resistance of the cell-patch sites and substrate capacitance were measured using impedance spectroscopy. The resistance of the microfabricated apertures ranged from 200 k/spl Omega/ to 47 M/spl Omega/ for apertures ranging from 12 /spl mu/m to 750 nm, respectively. The substrate capacitance was 17.2 pF per mm/sup 2/ of fluid contact area for substrates with a 2-/spl mu/m-thick layer of silicon dioxide. In addition, the ability of the planar patch-clamp substrates to form high-resistance seals in excess of 1 G/spl Omega/ has been confirmed using Chinese hamster ovary cells (CHO-K1). Testing shows that the microfluidic components are appropriate for driving human embryonic kidney cells (HEK 293) to patch apertures, for trapping cells on patch apertures, and for exchanging the extracellular fluid environment.
Structure of the heterogeneous L-S junction region of human cytomegalovirus strain AD169 DNA (1984)

The genome of human cytomegalovirus strain AD169 contains a region of heterogeneity located at the junction between the long (L) and short (S) components of the viral DNA. Twelve cloned L-S junction fragments were studied by using the restriction enzymes HaeII and XhoI. The region of heterogeneity was localized within a single HaeII restriction fragment. The enzyme XhoI was used to subdivide this region and revealed the presence of three types of heterogeneity within the junction fragments. Each of the cloned junction fragments contained one of the following fragments: 0.553, 0.95, or 1.35 kilobase pairs (referred to as class I heterogeneity). Class II heterogeneity was defined as the presence of tandem duplications of class I fragments. In addition, a variable number (0 to 5) of a 0.2-kbp fragment (class III heterogeneity) was observed. Mapping of these fragments with partial XhoI digestions revealed that the class I and class III heterogeneous fragments were adjacent. The DNA sequence of the smallest cloned L-S junction fragment was determined and analyzed. This junction fragment contained a single 0.553-kbp XhoI fragment and no copies of the 0.2-kbp fragment. The 0.553-kbp XhoI fragment was similar in structure to the a-sequences of herpes simplex virus types 1 and 2. In addition, a region of homology was found between the a sequences of herpes simplex virus types 1 and 2 and the 0.553-kbp XhoI fragment from the human cytomegalovirus junction.
Levels of soluble endothelium‐derived adhesion molecules in patients with sickle cell disease are associated with pulmonary hypertension, organ dysfunction, and mortality (2005)

Endothelial cell adhesion molecules orchestrate the recruitment and binding of inflammatory cells to vascular endothelium. With endothelial dysfunction and vascular injury, the levels of endothelial bound and soluble adhesion molecules increase. Such expression is modulated by nitric oxide (NO), and in patients with sickle cell disease (SCD), these levels are inversely associated with measures of NO bioavailability. To further evaluate the role of endothelial dysfunction in a population study of SCD, we have measured the levels of soluble endothelium-derived adhesion molecules in the plasma specimens of 160 adult patients with SCD during steady state. Consistent with a link between endothelial dysfunction and end-organ disease, we found that higher levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were associated with markers indicating renal dysfunction and hepatic impairment. Analysis of soluble intercellular cell adhesion molecule-1 (sICAM-1), sE-selectin and sP-selectin levels indicated partially overlapping associations with sVCAM-1, with an additional association with inflammatory stress and triglyceride levels. Importantly, increased soluble adhesion molecule expression correlated with severity of pulmonary hypertension, a clinical manifestation of endothelial dysfunction. Soluble VCAM-1, ICAM-1, and E-selectin were independently associated with the risk of mortality in this cohort. Our data are consistent with steady state levels of soluble adhesion molecules as markers of pulmonary hypertension and risk of death.
DNA sequence specificity of mitoxantrone (1994)

An in vitro transcription assay was used to determine the sequence specificity of binding of mitoxantrone to a 497 bp fragment of DNA containing the lac UV5 promoter. Transcriptional blockages of the E. coli RNA polymerase were observed dominantly prior to 5'-CpA sequences (64% occurrence), and to a lesser extent 5'-CpG sequences (29%). Overall, 93% of all blockage sites were prior to pyrimidine (3'-5') purine sequences. An effect of flanking sequences was evident since the blockage sites contained an A/T base pair 5' prior to the consensus CpA and CpG intercalation sites. The consensus sequences for the preferred mitoxantrone intercalation sites are therefore 5'-(A/T)CA and 5'-(A/T)CG. The location of transcriptional blockages one base pair prior to the intercalation site is consistent with the fact that the mitoxantrone side chains lie in the major groove.
Targeted delivery of RNA-cleaving DNA enzyme (DNAzyme) to tumor tissue by transferrin-modified, cyclodextrin-based particles (2004)

Short nucleic acid sequences specific to oncogene targets such as bcl-2, bcr-abl, and c-myc have been shown to exhibit specific anti-cancer activity in vitro through antigene or antisense activity. Efficient in vivo delivery of oligonucleotides remains a major limitation for the therapeutic application of these molecules. We report herein on the preparation of transferrin-modified nanoparticles containing DNAzymes (short catalytic single-stranded DNA molecules) for tumor targeting as well as their biodistribution using various methods of administration in the mouse. Linear, beta-cyclodextrin-based polymers are complexed with DNAyzme molecules to form sub-50 nm particles termed "polyplexes". The surface properties of the cyclodextrin-containing polyplexes are modified by exploiting the ability of the beta-cyclodextrin substructure and adamantane to form inclusion complexes. Accordingly, conjugates of adamantane with poly(ethylene glycol) (PEG) are prepared and combined with the polyplexes. The adamantane form inclusion complexes with the surface cyclodextrins of the polyplexes to provide a sterically stabilizing layer of PEG. The stabilized polyplexes are also modified with transferrin for increasing targeting to tumor cells expressing transferrin receptors. The preparation, characterization, and in vitro application of these nanoparticles are discussed. The transferrin-polyplexes containing fluorescently-labeled DNAzyme molecules are administered to tumor-bearing nude mice and their biodistribution and clearance kinetics are monitored using a fluorescence imaging system. Four methods of administration are studied: intraperitoneal bolus and infusion, intravenous bolus, and subcutaneous injection. DNAzymes packaged in polyplex formulations are concentrated and retained in tumor tissue and other organs, whereas unformulated DNAzyme is eliminated from the body within 24 hours post-injection. Intravenous and intraperitoneal bolus injections result in the highest fluorescent signal (DNAzyme) at the tumor site. Tumor cell uptake is observed with intravenous bolus injection only, and intracellular delivery requires transferrin targeting.
Re: Results of a Prospective, Randomized, Multicenter Study Evaluating Sacral Neuromodulation with InterStim Therapy Compared to Standard Medical Therapy at 6-Months in Subjects with Mild Symptoms of Overactive Bladder (2015)

No AccessJournal of UrologyAdult Urology1 Oct 2015Re: Results of a Prospective, Randomized, Multicenter Study Evaluating Sacral Neuromodulation with InterStim Therapy Compared to Standard Medical Therapy at 6-Months in Subjects with Mild Symptoms of Overactive Bladder Alan J. WeinMD, PhD (hon) Alan J. WeinAlan J. Wein More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.07.073AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Re: Results of a Prospective, Randomized, Multicenter Study Evaluating Sacral Neuromodulation with InterStim Therapy Compared to Standard Medical Therapy at 6-Months in Subjects with Mild Symptoms of Overactive Bladder." The Journal of Urology, 194(4), pp. 1051–1052 References 1 : Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety. J Urol2000; 163: 1849. Link, Google Scholar 2 : Sacral nerve stimulation for treatment of refractory urinary urge incontinence. Sacral Nerve Stimulation Study Group. J Urol1999; 162: 352. Link, Google Scholar © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 194Issue 4October 2015Page: 1051-1052Supplementary Materials Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alan J. Wein More articles by this author Expand All Advertisement PDF downloadLoading ...
Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. (1992)

ISGF-3 is an interferon-dependent positive-acting transcription factor that is cytoplasmically activated, possibly through direct interaction with the interferon receptor. The factor has been purified, its component proteins have been separated, and its peptide sequences have been obtained. From the sequences, degenerate oligonucleotide probes were constructed to screen for cDNA clones. Sequencing of the selected clones shows that the 91- and 84-kDa components represent two forms of a previously unknown (to our knowledge) protein. Several antibodies raised against these proteins prove that they indeed do encode protein components of ISGF-3. This work provides reagents to explore the modification of this cytoplasmically activated transcription factor.
Small interfering RNA and gene silencing in transgenic mice and rats (2002)

After short duplexes of synthetic 21-23 nt RNAs (siRNA) were reported to be effective in silencing specific genes, a vector-based approach for siRNAs was demonstrated in mammalian cultured cell lines. However, the effect of RNA interference (RNAi) on various differentiated cells in live animals remains unknown. In this report, we demonstrate that transgenically supplied siRNA can silence ubiquitously expressed enhanced green fluorescent protein in every part of the mouse and rat body. These results suggest that transgenic RNAi could function as an alternative method of gene silencing by applying homologous recombination to embryonic stem (ES) cells, and should be successful even in species where ES cell lines remain unestablished.
Phage-assisted continuous evolution of proteases with altered substrate specificity (2017)

Here we perform phage-assisted continuous evolution (PACE) of TEV protease, which canonically cleaves ENLYFQS, to cleave a very different target sequence, HPLVGHM, that is present in human IL-23. A protease emerging from ∼2500 generations of PACE contains 20 non-silent mutations, cleaves human IL-23 at the target peptide bond, and when pre-mixed with IL-23 in primary cultures of murine splenocytes inhibits IL-23-mediated immune signaling. We characterize the substrate specificity of this evolved enzyme, revealing shifted and broadened specificity changes at the six positions in which the target amino acid sequence differed. Mutational dissection and additional protease specificity profiling reveal the molecular basis of some of these changes. This work establishes the capability of changing the substrate specificity of a protease at many positions in a practical time scale and provides a foundation for the development of custom proteases that catalytically alter or destroy target proteins for biotechnological and therapeutic applications.Proteases are promising therapeutics to treat diseases such as hemophilia which are due to endogenous protease deficiency. Here the authors use phage-assisted continuous evolution to evolve a variant TEV protease with altered target peptide sequence specificities.
World-Driven Access Control for Continuous Sensing (2014)

Modern applications increasingly rely on continuous monitoring of video, audio, or other sensor data to provide their functionality, particularly in platforms such as the Microsoft Kinect and Google Glass. Continuous sensing by untrusted applications poses significant privacy challenges for both device users and bystanders. Even honest users will struggle to manage application permissions using existing approaches.
Controlling the sign of chromatic dispersion in diffractive optics with dielectric metasurfaces (2017)

Diffraction gratings disperse light in a rainbow of colors with the opposite order than refractive prisms, a phenomenon known as negative dispersion. While refractive dispersion can be controlled via material refractive index, diffractive dispersion is fundamentally an interference effect dictated by geometry. Here we show that this fundamental property can be altered using dielectric metasurfaces, and we experimentally demonstrate diffractive gratings and focusing mirrors with positive, zero, and hyper-negative dispersion. These optical elements are implemented using a reflective metasurface composed of dielectric nano-posts that provide simultaneous control over phase and its wavelength derivative. In addition, as a first practical application, we demonstrate a focusing mirror that exhibits a five-fold reduction in chromatic dispersion, and thus an almost three-times increase in operation bandwidth compared with a regular diffractive element. This concept challenges the generally accepted dispersive properties of diffractive optical devices and extends their applications and functionalities.
Constitutive and inducible mechanisms for synthesis and release of cytokines in immune cell lines (1996)

We found that production and release of two functionally antagonistic cytokines, TGF-beta and TNF-alpha, were regulated differently in the mast cell, T cell, and macrophage cell lines RBL-2H3, MLA-144, and U-937, respectively. TGF-beta was produced and released constitutively in all three cell lines. When, however, the cell lines were stimulated with Ag, LPS, or calcium ionophore plus PMA, acceleration of release and some additional production of TGF-beta were apparent. In contrast, TNF-alpha was produced and released only when these lines were stimulated. Although neither the glucocorticoid, dexamethasone, nor the protein kinase C inhibitor, Ro31-7549, suppressed constitutive production or release of TGF-beta, these agents inhibited TNF-alpha production and the inducible component of TGF-beta production noted above. The release of these cytokines, whether constitutive or inducible, was dependent on Golgi-processing as indicated by inhibition with brefeldin A. Therefore, although both types of cytokines were processed by Golgi, only TNF-alpha and the inducible component of TGF-beta production were protein kinase C or steroid-regulated processes. These findings suggested that constitutive and inducible pathways exist for production and release of cytokines and that the inducible pathways can be selectively suppressed by pharmacologic agents.
Reciprocity principle applicable to reflected radiance measurements and the searchlight problem (1999)

In a recent paper by Di Girolamo et al. [J. Geophys. Res. D 103, 8795 (1998)] a heuristic argument was used to derive a reciprocity principle applicable to reflected solar radiation measurements. Here a formal derivation of this reciprocity principle is presented. It is also demonstrated that a purely spatial reciprocal relationship exists between one-dimensional radiative transfer theory and the three-dimensional searchlight problem for horizontally homogeneous media.
Synthesis of Oxygen Heterocycles via a Palladium-Catalyzed C−O Bond-Forming Reaction (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSynthesis of Oxygen Heterocycles via a Palladium-Catalyzed C−O Bond-Forming ReactionMichael Palucki, John P. Wolfe, and Stephen L. BuchwaldView Author Information Department of Chemistry Massachusetts Institute of Technology Cambridge, Massachusetts 02139 Cite this: J. Am. Chem. Soc. 1996, 118, 42, 10333–10334Publication Date (Web):October 23, 1996Publication History Received19 July 1996Published online23 October 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja962408vhttps://doi.org/10.1021/ja962408vrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views5870Altmetric-Citations256LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Alcohols,Aromatic compounds,Cyclization,Hydrocarbons,Organic reactions Get e-Alerts