gebhart/patrepeval huggingface dataset:
Delivery of125I-NGF to the Brain via the Olfactory Route (1997)

AbstractThe blood-brain barrier presents a major problem in the administration and testing of neurotropins as it prevents a sufficient concentration of these potential therapeutic agents from reaching the target areas of the human brain. The olfactory neuroepithelium is the only area of the body in which an extension of the central nervous system comes into direct contact with the environment. Following intranasal administration of 125I-labeled nerve growth factor (125I-NGF), radiolabel appeared rapidly in the olfactory bulb and other brain regions. Radiolabel accumulation in the olfactory bulb of the brain was a linear function of the intranasal dose and of the radiolabel concentration in the olfactory epithelium. Concentration of radiolabel in the olfactory bulb and brain with intranasal administration, but not with intravenous administration, suggests direct transport of label into the brain along the olfactory route following intranasal administration. The rapid appearance of label in the olfactory bulbs, cerebrum, and brain stem is more consistent with entry of label through intercellular clefts in the olfactory epithelium and extracellular transport along the olfactory neural pathway to reach the cerebrospinal fluid and brain than with uptake by olfactory neurons and subsequent intracellular axonal transport. At least 80% of the radiolabel found in the brain following intranasal delivery of 125I-NGF precipitates in cold 5% trichloroacetic acid, suggesting that a significant amount of intact NGF reaches the brain. Preliminary studies using a sandwich enzyme-linked immunosorbent assay have confirmed the uptake of NGF into the brain following intranasal but not intravenous administration to rats. This is the first evidence for noninvasive delivery of unconjugated NGF to the brain.Key Words : Alzheimer's DiseaseBrainDrug DeliveryIntranasalNerve Growth FactorOlfactory
Reorganization of hydrated collagen lattices by human skin fibroblasts (1984)

Fibroblasts were cultured on top of or at the bottom of hydrated collagen lattices. Shortly after initially interacting with the collagen lattices, fibroblasts appeared to attach to individual collagen fibrils and in many cases cell processes were found wrapped around clusters of collagen fibrils. Tension generated by cells during spreading resulted in proximal collagen fibrils becoming aligned distal in the plane of spreading and more densely packed. During subsequent culture, the collagen fibrils to the cells underwent a similar reorganization and the lattice thinned to one-tenth of its original thickness. The rate of thinning was similar regardless of whether the cells were originally above or at the bottom of the lattices. The presence of cells distributed throughout the lattice was unnecessary for lattice reorganization to occur. When the lattices were allowed to come off the underlying substratum, compaction of the collagen gels was observed, and the resulting matrix had the typical appearance of dermis as observed by both light and electron microscopy. Collagen fibrils associated with the cell surface often appeared to be under tension and, in regions of close fibril binding, there was a prominent reorganization of submembranous microfilaments. It is suggested that reorganization of the collagen lattice by fibroblasts may depend upon secreted cell factors as well as physical forces generated by the cells.
Human umbilical cord conditioned medium: a stimulus for human CFU-G. (1984)

Segments of human umbilical cord have been used to prepare a highly active conditioned medium (HUCCM) for in vitro human granulopoiesis and have been compared with human placenta conditioned medium (HPCM) and feeder layers. The HUCCM produced more colonies on day 7 than HPCM (P less than 0.001), and colonies consisted almost exclusively (over 98%) of granulocytic cells by both morphological and cytochemical analysis. The HUCCM-stimulated colonies have a short culture life, the number of colonies being maximal on day 7 of culture with few colonies remaining on day 10. The main source of the colony-stimulating activity in the umbilical cord was found in the Wharton's Jelly component.
Hydrolysis of Phostonates1,2 (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydrolysis of Phostonates1,2Anatol Eberhard and F. H. WestheimerCite this: J. Am. Chem. Soc. 1965, 87, 2, 253–260Publication Date (Print):January 1, 1965Publication History Published online1 May 2002Published inissue 1 January 1965https://pubs.acs.org/doi/10.1021/ja01080a021https://doi.org/10.1021/ja01080a021research-articleACS PublicationsRequest reuse permissionsArticle Views721Altmetric-Citations41LEARN 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
HARDIMAN I ARM TEST - HARDIMAN I PROTOTYPE PROJECT (1969)

Abstract : A discussion is presented of the test and evaluation of the HARDIMAN I left arm assembly. The HARDIMAN I prototype is powered exoskeletal harness which will amplify man's strength and endurance while retaining his versatility and dexterity. The objective of the arm test was to investigate human factors and servo performance while lifting a load.
Remission and active disease in rheumatoid arthritis: Defining criteria for disease activity states (2005)

New criteria for levels of RA disease activity were determined and internally validated. These criteria, which are based on current and explicit expert judgment, are valuable in this era of rapidly advancing therapeutic approaches.
Anion Binding and Controlled Aggregation of Human Interleukin-1 Receptor Antagonist (2005)

Highly concentrated human recombinant interleukin-1 receptor antagonist (IL-1ra) aggregates at elevated temperature without perturbation in its secondary structure. The protein aggregation can be suppressed depending on the buffer ionic strength and the type of anion present in the sample solution. Phosphate is an approximately 4-fold weaker suppressant than either citrate or pyrophosphate on the basis of the measured protein aggregation rates. This is in agreement with the strength of protein-anion interactions at the IL-1ra single anion-binding site as judged by the estimated dissociation constant values of 2.9 mM, 3.8 mM, and 13.7 mM for pyrophosphate, citrate, and phosphate, respectively. The strength of binding also correlates with the anion size and with the number of ionized groups available per molecule at a given pH. Affinity probing of IL-1ra with methyl acetyl phosphate (MAP) in combination with proteolytic digestion and mass spectral analysis show that an anion-binding site location on the IL-1ra surface is contributed by lysine-93 and lysine-96 of the loop 84-98 as well as by lysine-6 of the unstructured N-terminal region 1-7. The replacement of lysine-93 with alanine by site-directed mutagenesis results in dramatically suppressed IL-1ra aggregation. Furthermore, when the unstructured N-terminal region of IL-1ra is removed by limited proteolysis, a 2-fold increase in the time course of the aggregation lag phase is observed for the truncated protein. An anion-controlled mechanism of IL-1ra aggregation is proposed by which the anion competition for the protein cationic site prevents formation of intermolecular cation-pi interactions and, thus, interferes with the protein asymmetric self-association pathway.
Distance Language Learning (2004)

This article provides a report on NetMeeting as an appropriate fourth-generation tool for interactive language learning in distance mode. It follows on earlier research by Wang and Sun (2000, 2001) on the most urgent problem facing distance language education—lack of provision of oral-visual interaction and the emergence of a fourth-generation distance language learning. The article proceeds through three cumulative parts. The first part is a definitional context of interaction and computer-mediated communication (CMC) as a framework for the article. The second part focuses on interaction as a core problem in the language learning literature and suggests a new taxonomy through CMC in terms of the potential for written, oral, and, more recently, oral-visual interaction. The third part, and the substance of the article, is an empirical investigation of Internet-based videoconferencing tools focusing on NetMeeting as the most appropriate one in terms of meeting criteria proposed for such tools.
Using Go for Statistical Analyses (2004)

In this paper we use meta-data packages from the Bioconductor Project to carry out statistical analyses of gene expression data. But would like to note that the potential scope of these applications is much broader and many of the methods described here could be applied to other types of high-throughput data. To provide context we make use of data from an investigation into acute lymphoblastic leukemia.
Eradication of large solid tumors in mice with an immunotoxin directed against tumor vasculature. (1993)

Antibody-based therapy of solid tumors has met with limited success, chiefly because solid tumors are relatively impermeable to macromolecules. This problem could be circumvented by attacking the readily accessible endothelial cells of the tumor vascular bed. We have developed a model to test this "vascular targeting" approach in which cytokine gene transfection of the tumor cells causes them to induce an experimental marker selectively on tumor vascular endothelium. An anti-tumor endothelial cell immunotoxin caused complete occlusion of the tumor vasculature and dramatic regressions of large solid tumors. By contrast, a conventional anti-tumor cell immunotoxin of equivalent in vitro potency produced only minor, transient antitumor effects but, when combined, the two immunotoxins induced permanent complete remissions in over half of the animals. These experiments indicate that immunotoxins directed against recently described markers on vascular endothelial cells in human tumors could provide a general treatment for solid tumors in humans.
Mouse PeP: A novel peroxisomal protein linked to myoblast differentiation and development (2002)

The identification of several peroxisomal proteins in the past decade has deepened our understanding of the biology of peroxisomes and their involvement in human disorders. We report the cloning and expression pattern during the mouse development of a cDNA encoding a novel protein, named PeP, and show that its product is imported specifically to the peroxisome matrix in a variety of cell types. We also demonstrate that PeP is imported to the organelle through the PEX5 receptor pathway, which indicates that the C-terminal tripeptide SKI behaves as a type 1 peroxisomal targeting signal (PTS1). PeP expression is tightly regulated, as shown by Northern and in situ hybridization experiments. Thus during embryonic development in the mouse, PeP mRNA is detected almost exclusively in the skeletal muscle, whereas in adult mice, strong expression is also found in the heart and brain. In addition, PeP mRNA accumulation is induced after myoblast differentiation in vitro, when myotube formation is promoted. Sequence analysis reveals that PeP has no significant homology to any known protein, except for a short stretch of amino acids containing the fingerprint of the fibronectin type III superfamily, a domain present in proteins often related to molecular and cellular recognition and binding processes. Thus our data suggest a connection between the function of PeP and murine cell differentiation and development.
Expression in Escherichia coli of biologically active enzyme by a DNA sequence coding for the human plasminogen activator urokinase. (1981)

We have isolated clones of Escherichia coli strain K-12 that contain a hybrid pBR322 plasmid having a 4.2-kilobase insert of a DNA transcript of the mRNA of human plasminogen activator, urokinase. The bacterially produced enzyme has properties similar to those of urokinase from human fetal kidney cells. Both enzymes occur in discrete forms ranging from 32,000 to 150,000 daltons in size. They react with antibody to purified urokinase from human kidney cells, bind to a benzamidine-Sepharose column, and induce plasminogen-dependent lysis of a fibrin clot.
tert-Butylsulfonyl (Bus), a New Protecting Group for Amines (1997)

ADVERTISEMENT RETURN TO ISSUEPREVNotetert-Butylsulfonyl (Bus), a New Protecting Group for AminesPu Sun, Steven M. Weinreb, and Maoyu ShangView Author Information Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802 Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556 Cite this: J. Org. Chem. 1997, 62, 24, 8604–8608Publication Date (Web):November 28, 1997Publication History Received5 August 1997Published online28 November 1997Published inissue 1 November 1997https://pubs.acs.org/doi/10.1021/jo971455ihttps://doi.org/10.1021/jo971455ibrief-reportACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views5649Altmetric-Citations120LEARN 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 (2)»Supporting Information Supporting Information SUBJECTS:Amines,Anions,Protective groups,Reaction products,Sulfones Get e-Alerts
Selective Small Molecule Compounds Increase BMP-2 Responsiveness by Inhibiting Smurf1-mediated Smad1/5 Degradation (2014)

The ubiquitin ligase Smad ubiquitination regulatory factor-1 (Smurf1) negatively regulates bone morphogenetic protein (BMP) pathway by ubiquitinating certain signal components for degradation. Thus, it can be an eligible pharmacological target for increasing BMP signal responsiveness. We established a strategy to discover small molecule compounds that block the WW1 domain of Smurf1 from interacting with Smad1/5 by structure based virtual screening, molecular experimental examination and cytological efficacy evaluation. Our selected hits could reserve the protein level of Smad1/5 from degradation by interrupting Smurf1-Smad1/5 interaction and inhibiting Smurf1 mediated ubiquitination of Smad1/5. Further, these compounds increased BMP-2 signal responsiveness and the expression of certain downstream genes, enhanced the osteoblastic activity of myoblasts and osteoblasts. Our work indicates targeting Smurf1 for inhibition could be an accessible strategy to discover BMP-sensitizers that might be applied in future clinical treatments of bone disorders such as osteopenia.
Persisting zones of slow impulse conduction in developing chicken hearts. (1992)

We performed a correlative electrophysiological and immunohistochemical study of embryonic chicken hearts during the septational period (Hamburger and Hamilton stages 13-31 [2-7 days of incubation]). The analyses yield conclusive evidence for slow conduction, up to 7 days of development, in the outflow tract, in the atrioventricular canal, and in the sinoatrial junction. The conduction velocity remains approximately 1 cm/sec in the outflow tract and increases in the ventricle 20-fold to approximately 20 cm/sec between 2 and 7 days of development. Transmembrane potentials of myocytes in the outflow tract and atrioventricular canal slowly rise (less than 5 V/sec), whereas in the atrium and ventricle, the upstroke velocity is eightfold to 13-fold higher. In the outflow tract, repolarization is completed only after the start of the next cycle. Because of the persistence of slow conduction, the myocardium flanking the developing atria and ventricle is thought to represent segments of persisting "primary" myocardium, whereas the more rapidly conducting "working" myocardium of the ventricle and atria is thought to represent more advanced stages of myocardial differentiation. The persisting primary myocardium was characterized by a continued coexpression of both the atrial and ventricular isoforms of myosin heavy chain. The developing atria and ventricle could be demarcated morphologically from the primary myocardium because the free walls of these segments only express their respective isoforms of myosin heavy chain. The slowly conducting myocardial zones appear to be essential for the function of the embryonic heart because 1) they provide the septating heart with alternating segments of slow and relatively fast conduction necessary for consecutive contraction of the atrial and ventricular segments and 2) their sphincterlike prolonged peristaltic contraction pattern can substitute for the adult type of one-way valves that start to develop at the end of septation.
Conditional-Suicide Containment System for Bacteria Which Mineralize Aromatics (1991)

A model conditional-suicide system to control genetically engineered microorganisms able to degrade substituted benzoates is reported. The system is based on two elements. One element consists of a fusion between the promoter of the Pseudomonas putida TOL plasmid-encoded meta-cleavage pathway operon (P(m)) and the lacI gene encoding Lac repressor plus xylS, coding for the positive regulator of P(m). The other element carries a fusion between the P(tac) promoter and the gef gene, which encodes a killing function. In the presence of XylS effectors, LacI protein is synthesized, preventing the expression of the killing function. In the absence of effectors, expression of the P(tac)::gef cassette is no longer prevented and a high rate of cell killing is observed. The substitution of XylS for XylSthr45, a mutant regulator with altered effector specificity and increased affinity for benzoates, allows the control of populations able to degrade a wider range of benzoates at micromolar substrate concentrations. Given the wide effector specificity of the key regulators, the wild-type and mutant XylS proteins, the system should allow the control of populations able to metabolize benzoate; methyl-, dimethyl-, chloro-, dichloro-, ethyl-, and methoxybenzoates; salicylate; and methyl- and chlorosalicylates. A small population of genetically engineered microorganisms became Gef resistant; however, the mechanism of such survival remains unknown.
The Role of Angiopoietins as Potential Therapeutic Targets in Renal Cell Carcinoma (2014)

Angiopoietin 2 (Ang2) is a secreted glycoprotein upregulated at sites of angiogenesis and has been implicated in cancer neovascularization. Recent studies have suggested efficacy of combined Ang and vascular endothelial growth factor receptor (VEGFR) inhibition for patients with metastatic renal cell carcinoma (mRCC). We measured Ang2 expression in human tissue and plasma, and tested the effect of dual Ang1/2 (trebananib; AMG386) or Ang2 alone (L1-7) inhibition with VEGFR inhibition on murine RCC growth and blood flow. Ang2 levels were higher in human tumors than normal tissues with RCC ranking highest for Ang2 expression across all tumor types tested. Plasma Ang2 was significantly higher in patients with mRCC compared to controls or patients with stage I disease. Plasma Ang2 decreased with sunitinib treatment and increased at time of disease progression. In the RCC mouse, dual Ang1/2 and Ang2 inhibition improved the activity of sunitinib. Combined Ang1/2 and VEGFR inhibition prevented the resumption of blood flow associated with sunitinib resistance. Thus, Ang2 inhibition, independent of Ang1 inhibition, improves the activity of sunitinib and plasma Ang2 increases in the setting of progression on sunitinib possibly contributing to resistance. Further, arterial spin-labeled perfusion magnetic resonance imaging might be a non-invasive marker of the antiangiogenic activity of Ang inhibitors.
Sub-50 nm P-channel FinFET (2001)

High-performance PMOSFETs with sub-50-nm gate-length are reported. A self-aligned double-gate MOSFET structure (FinFET) is used to suppress the short-channel effects. This vertical double-gate SOI MOSFET features: 1) a transistor channel which is formed on the vertical surfaces of an ultrathin Si fin and controlled by gate electrodes formed on both sides of the fin; 2) two gates which are self-aligned to each other and to the source/drain (S/D) regions; 3) raised S/D regions; and 4) a short (50 nm) Si fin to maintain quasi-planar topology for ease of fabrication. The 45-nm gate-length p-channel FinFET showed an I/sub dsat/ of 820 /spl mu/A//spl mu/m at V/sub ds/=V/sub gs/=1.2 V and T/sub ox/=2.5 mm. Devices showed good performance down to a gate-length of 18 nm. Excellent short-channel behavior was observed. The fin thickness (corresponding to twice the body thickness) is found to be critical for suppressing the short-channel effects. Simulations indicate that the FinFET structure can work down to 10 nm gate length. Thus, the FinFET is a very promising structure for scaling CMOS beyond 50 nm.
Chemical aspects of UV-induced crosslinking of proteins to nucleic acids. Photoreactions with lysine and tryptophan (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemical aspects of UV-induced crosslinking of proteins to nucleic acids. Photoreactions with lysine and tryptophanIsao Saito and Teruo MatsuuraCite this: Acc. Chem. Res. 1985, 18, 5, 134–141Publication Date (Print):May 1, 1985Publication History Published online1 May 2002Published inissue 1 May 1985https://pubs.acs.org/doi/10.1021/ar00113a002https://doi.org/10.1021/ar00113a002research-articleACS PublicationsRequest reuse permissionsArticle Views821Altmetric-Citations59LEARN 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