gebhart/patrepeval huggingface dataset:
Progress made in non-invasive insulin delivery (1996)

Insulin is used in the treatment of Diabetes Mellitus. It is a small protein having a molecular weight of 5808. An ideal insulin delivery system should deliver insulin in a pulsatile manner, control the rate of insulin delivery depending on blood glucose concentration, should be delivered into the portal circulation. In addition there should be minimum intraindividual variation, it should be easy to administer and economical. The current insulin treatment does not meet these requirements, hence alternate routes are being developed. The oral delivery though the most convenient and acceptable route however is degraded by intestinal enzymes therefore. insulin was administered with enzyme inhibitors, coated with azoaromatic polymer in the form of nanocapsules, liposomes, microemulsions. But oral delivery showed variable responses and could lead to immunological problems. Increased absorption of insulin by the nasal mucosa was tried by adding various surfactants and by increasing the time of contact. However these surfactants caused irritation and could lead to anti-insulin antibodies. The advantage of pulmonary aerosol is that significant absorption of insulin takes place without the use of absorption promoting agents. The long term effects of this delivery has to be assessed. Besides these the other routes tried are ocular, transdermal. buccal, rectal and vaginal.
Typing of genetic variants of alpha 1-antitrypsin by electrofocusing. (1982)

Journal Article Typing of genetic variants of alpha 1-antitrypsin by electrofocusing. Get access J O Jeppsson, J O Jeppsson Search for other works by this author on: Oxford Academic Google Scholar B Franzén B Franzén Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 28, Issue 1, 1 January 1982, Pages 219–225, https://doi.org/10.1093/clinchem/28.1.219 Published: 01 January 1982
The self-perpetuating tau truncation circle (2012)

Pathological truncations of human brain proteins represent the common feature of many neurodegenerative disorders including AD (Alzheimer's disease), Parkinson's disease and Huntington's disease. Protein truncations significantly change the structure and function of these proteins and thus can engender their pathological metamorphosis. We have shown previously that truncated forms of tau protein are contained in the core of the paired helical filaments that represent the main constituent of neurofibrillary pathology. Recently, we have identified truncated tau species of a different molecular signature. We have found that tau truncation is not produced by a random process, but rather by highly specific proteolytic cleavage and/or non-enzymatic fragmentation. In order to characterize the pathophysiology of AD-specific truncated tau species, we have used a transgenic rat model for AD expressing human truncated tau. Expression of the tau protein induces the formation of novel truncated tau species that originate from both transgenic human tau and endogenous rat tau proteins. Moreover, these truncated tau proteins are found exclusively in the misfolded fraction of tau, suggesting that they actively participate in the tau misfolding process. These findings corroborate further the idea that the appearance of truncated tau species starts a self-perpetuating cycle of further tau protein truncation leading to and accelerating tau misfolding and formation of neurofibrillary pathology.
P-Glycoprotein Acts as an Immunomodulator during Neuroinflammation (2009)

Our data demonstrate that P-gp downmodulates DC function through the regulation of pro-inflammatory cytokine secretion, resulting in an impaired immune response. Taken together, our work highlights a new physiological role for P-gp as an immunomodulatory molecule and reveals a possible new target for immunotherapy.
Design, synthesis, and biological activity of N-alkylated analogue of NCL1, a selective inhibitor of lysine-specific demethylase 1 (2014)

A hybridization of NCL1 and compound <bold>5</bold> led to the identification of a potent lysine-specific demethylase 1 inhibitor <bold>5</bold>.
Genetic analysis of the human tumor necrosis factor alpha/cachectin promoter region in a macrophage cell line. (1989)

The 615-bp 5' flanking region of the human TNF-alpha/cachectin gene was isolated and ligated to the luciferase reporter gene. In addition, a series of truncated promoter constructs was generated by exonuclease III digestion. The promoter activity of these constructs was studied in a transient transfection system using the TNF-alpha-producing U937 cell line. Full-length and truncated TNF promoter constructions extending from -615 to -95 bp relative to the transcription start site (TSS) could be induced by phorbol esters. A construct truncated to within 36 bp of the TSS (and within 11 bp of the TATAA box) was inactive. Therefore, the phorbol ester responsive is localized in the TNF/cachectin promoter to a relatively short region proximal to the TATAA box.
ADAM-TS5, ADAM-TS6, and ADAM-TS7, Novel Members of a New Family of Zinc Metalloproteases (1999)

We report the primary structure of three novel, putative zinc metalloproteases designated ADAM-TS5, ADAM-TS6, and ADAM-TS7. All have a similar domain organization, comprising a preproregion, a reprolysin-type catalytic domain, a disintegrin-like domain, a thrombospondin type-1 (TS) module, a cysteine-rich domain, a spacer domain without cysteine residues, and a COOH-terminal TS module. These genes are differentially regulated during mouse embryogenesis and in adult tissues, with Adamts5 highly expressed in the peri-implantation period in embryo and trophoblast. These proteins are similar to four other cognate gene products, defining a distinct family of human reprolysin-like metalloproteases, the ADAM-TS family. The other members of the family are ADAM-TS1, an inflammation-induced gene, the procollagen I/II amino-propeptide processing enzyme (PCINP, ADAM-TS2), and proteins predicted by the KIAA0366 and KIAA0688 genes (ADAM-TS3 and ADAM-TS4). Individual ADAM-TS members differ in the number of COOH-terminal TS modules, and some have unique COOH-terminal domains. The ADAM-TS genes are dispersed in human and mouse genomes.
Understanding Limits on Fin Aspect Ratios in Counterflow Microchannel Arrays Produced by Diffusion Bonding (2006)

This paper investigates the manufacturability limits of fin aspect ratios within two-fluid counter-flow microchannel arrays based on the stress state between laminae during diffusion bonding. In prior papers, it has been shown that the diffusion bonding of two-fluid systems by microlamination can result in regions of the device that do not directly transmit bonding pressure and, consequently, result in unbonded regions leading to device leakage. A finite element model is used to analyze the stress state between laminae during diffusion bonding. The stress state is used to determine the critical stress necessary for diffusion bonding to occur in areas not receiving direct bonding pressure. Model results are compared with experimental results over a wide range of counter-flow geometries. It has been found generally that a compressive stress state must exist in every part of the geometry in order to produce leak-free bonds. Implications of this finding on the design of two-fluid microchannel arrays are discussed.
A calculus for finely layered anisotropic media (1989)

Abstract Matrix algebra and group theory combine to offer a formalism for the simple calculation of the elastic, anisotropic, homogeneous medium which is equivalent, in the long-wavelength limit, to a heterogeneous distribution of fine layers, each layer itself an elastic anisotropic medium. The properties of each anisotropic constituent in a set of fine layers map to an element of a commutative group. A reverse mapping returns the material properties of the constituent. Adding group elements gives the group element for the homogeneous medium equivalent to a heterogeneous set of layers. Addition of an inverse element--that is subtraction--provides the means to remove a set of layers from an anisotropic medium; then, if the remaining layer is a stable anisotropic medium, a valid decomposition of the original medium into anisotropic constituents is obtained. Within the group structure, eight subgroups corresponding to eight types of elastic symmetry systems may be identified, immediately yielding the symmetry of the equivalent medium, given the symmetry of its constituents. Sets of parallel fractures or aligned microcracks are also represented as group elements, allowing fractures and anisotropic rocks to be manipulated in a consistent and uniform manner. These group elements depend on at most six fracture parameters and are independent of the properties of the material in which the fractures are embedded. Multiple sets of fractures are easily taken into account by rotating (back in model space) a rock to a coordinate system appropriate to each fracture system, and then adding the appropriate fracture system group element.
Differential capacitance of the double layer at the electrode/ionic liquids interface (2010)

The differential capacitance of the electrical double layer at glassy carbon, platinum and gold electrodes immersed in various ionic liquids was measured using impedance spectroscopy. We discuss the influence of temperature, the composition of the ionic liquids and the electrode material on the differential capacitance/potential curves. For different systems these curves have various overall shapes, but all include several extremes and a common minimum near the open circuit potential. We attribute this minimum to the potential of zero charge (PZC). Significantly, the differential capacitance generally decreases if the applied potential is large and moving away from the PZC. This is attributed to lattice saturation [A. A. Kornyshev, J. Phys. Chem. B, 2007, 111, 5545] effects which result in a thicker double layer. The differential capacitance of the double layer grows and specific adsorption diminishes with increasing temperature. Specific adsorption of both cations and anions influences the shapes of curves close to the PZC. The general shape of differential capacitance/potential does not depend strongly on the identity of the electrode material.
Novel 1-Phenylcycloalkanecarboxylic Acid Derivatives Are Potent and Selective .sigma.1 Ligands (1994)

Carbetapentane (1, 2-[2-(diethylamino)ethoxy]ethyl 1-phenyl-1-cyclopentanecarboxylate) binds with high affinity to sigma sites and is a potent antitussive, anticonvulsant, and spasmolytic agent. However, carbetapentane interacts at muscarinic binding sites as well, and it is not clear whether either of these receptor systems is involved in the mechanism(s) of action(s) of this drug. In an attempt to determine whether these psychoactivities can be attributed to interaction at sigma sites, a series of carbetapentane analogs were prepared. Phenyl ring substitution; contraction, expansion, and replacement with a methyl group of the cyclopentyl ring; replacement of the carboxylate function with an amide, methyl ether, and methylamine; and replacement of the N,N-diethyl substituent with a morpholino or piperidino moiety were investigated. All of these novel analogs were evaluated for binding to sigma 1 and sigma 2 sites, and comparison of binding at muscarinic m1 and m2 and PCP (1-(1-phenylcyclohexyl)piperidine) receptors was performed. All of the compounds were selective for sigma 1 over sigma 2 sites, with the three most selective analogs being compounds 34 (65-fold), 35 (78-fold), and 39 (51-fold). None of the compounds were active at PCP sites, and chemical modification including (1) replacing the ester function, (2) replacing the cyclopentyl ring with a smaller ring system (cyclopropyl) or a methyl group, and (3) replacing the diethylamino moiety with a morpholino group resulted in > 220-fold selectivity over muscarinic receptor binding. Therefore, several of these novel compounds are potent, sigma 1-selective ligands which can now be investigated as potential antitussive, anticonvulsant, and antiischemic agents. These studies may reveal whether sigma 1 sites play a role in the pharmacological actions of these drugs.
Equilibrium denaturation of pituitary- and recombinant-derived bovine growth hormone (1985)

Holladay and co-workers [Holladay, L. A., Hammonds, R. G., & Puett, D. (1974) Biochemistry 13, 1653-1661] reported the presence of an equilibrium intermediate in the guanidine hydrochloride (GdnHCl) induced denaturation of pituitary-derived bovine growth hormone (p-bGH). Since then, numerous reports have appeared demonstrating the inherent heterogeneity in p-bGH. In this report we show that a standard preparation of p-bGH can be separated into two components of almost equal abundance differing in molecular weight by approximately 1000. Each of these two components could give rise to different denaturation transitions which would be interpreted as evidence for equilibrium intermediates. We report here the equilibrium denaturation of bGH produced by Escherichia coli through recombinant DNA technology. The recombinant-derived bGH (r-bGH) is more homogeneous than that derived from pituitary sources and is greater than 95% a single polypeptide entity. Nevertheless, the GdnHCl-induced denaturation profiles of both recombinant bGH and pituitary bGH are very similar. The presence of equilibrium intermediates is verified by the asymmetry of the denaturation transition as measured by size-exclusion high-performance liquid chromatography and by noncoincidence of the denaturation transitions as observed by ultraviolet absorbance, fluorescence intensity, and circular dichroism. These findings conclusively show that the secondary structure of bovine growth hormone is more stable than the tertiary structure and is consistent with a framework model of protein folding.
Imino‐bridged heterocycles. VII.N‐aminobenzocycloheptapyridinimines (1986)

Abstract Condensation of anhydrous hydrazine with a variety of benzocycloheptapyridinones led to N ‐aminobenzocycloheptapyridinimines. Regiospecific ring closures occurred in all the systems investigated.
A Live Attenuated Severe Acute Respiratory Syndrome Coronavirus Is Immunogenic and Efficacious in Golden Syrian Hamsters (2008)

The immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (SARS) coronavirus lacking the E gene (rSARS-CoV-DeltaE) were studied using hamsters. Hamsters immunized with rSARS-CoV-DeltaE developed high serum-neutralizing antibody titers and were protected from replication of homologous (SARS-CoV Urbani) and heterologous (GD03) SARS-CoV in the upper and lower respiratory tract. rSARS-CoV-DeltaE-immunized hamsters remained active following wild-type virus challenge, while mock-immunized hamsters displayed decreased activity. Despite being attenuated in replication in the respiratory tract, rSARS-CoV-DeltaE is an immunogenic and efficacious vaccine in hamsters.
An LRR Receptor Kinase Involved in Perception of a Peptide Plant Hormone, Phytosulfokine (2002)

The sulfated peptide phytosulfokine (PSK) is an intercellular signal that plays a key role in cellular dedifferentiation and proliferation in plants. Using ligand-based affinity chromatography, we purified a 120-kilodalton membrane protein, specifically interacting with PSK, from carrot microsomal fractions. The corresponding complementary DNA encodes a 1021-amino acid receptor kinase that contains extracellular leucine-rich repeats, a single transmembrane domain, and a cytoplasmic kinase domain. Overexpression of this receptor kinase in carrot cells caused enhanced callus growth in response to PSK and a substantial increase in the number of tritium-labeled PSK binding sites, suggesting that PSK and this receptor kinase act as a ligand-receptor pair.
National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment (1996)

N 1988, THE National Cancer Institute-sponsored Working Group (NCI-WC) on chronic lymphocytic leukemia (CLL) published guidelines for the design and conduct of clinical trials in CLL with two major objectives: first, to facilitate comparisons of results of clinical trials in CLL by providing standardized eligibility, response, and toxicity criteria; and, second, to encourage a framework on which to evaluate new scientific studies related to our increasing understanding of the biology and immunology of this disease.' These guidelines were rapidly adopted by the majority of the clinical trials community, and were also used by the Food and Drug Administration during its evaluation process for the approval of fludarabine. The differences between these guidelines and those subsequently published by the International Working Group on CLL (IWCLL), which were general-practice recommendations' are listed in Table 1. For diagnosis, the NCI-WC requires a lymphocyte count of 5 X loy& which is lower than the 10 X 109/L required by the IWCLL, unless the lymphocytes are B cells and the bone marrow is involved. To be considered a complete remission (CR), the NCI-WC criteria specify that less than 30% lymphocytes must be present in the bone marrow, with a recommendation that the clinical significance of lymphoid nodules be assessed prospectively (Table 1); the IWCLL allows focal infiltrates or nodules in the bone marrow aspirate and biopsy for CR. The IWCLL uses a shift in clinical stage as the sole index of partial remission (PR), whereas the NCI-WC provides more specific criteria and recommends validation of the relevance of stage shift. The major differences were the well-defined criteria in the NCI guidelines regarding when to initiate therapy, hematologic toxicity, and other important components for clinical trials design. The purpose of this report is to present those revisions as considered necessary in view of advances in the past 8 years. Many of these revisions evolved as the guidelines were used in a systematic fashion in large clinical trials and, also, with the experience following the use of newer, more effective agents, such as fludarabine.' Although this report will focus on those changes recommended by the NCI-sponsored CLL Working Group, it will include sufficient details from the original guidelines so that the reader would find it a complete document by itself without having to refer to the older version.
The Growth and Characterization of Silicon/Silicon Carbide Heteroepitaxial Films on Silicon Substrates by Rapid Thermal Chemical Vapor Deposition (1996)

SiC and Si heteroepitaxial films were sequentially deposited on Si substrates to form Si/SiC/Si multilayer structures using a refined rapid thermal chemical vapor deposition (RTCVD) technology. Refined RTCVD is a combination of a graded composition process with rapid thermal chemical vapor deposition. The optimum growth conditions and characteristics of the as-grown films in the Si/SiC/Si multilayers were studied by structrual (X-ray, TEM) and electrical (four-point probe , Hall measurement) methods. N-Si/n-SiC/p-Si double-heterojunction diodes (DHD) were fabricated to determine the suitability of the multilayer films for device applications. Analysis of the I – V characteristics of the diode indicates that fine control of the thickness of the graded layers without degrading the crystallinity of the films results in high-quality heteroepitaxial SiC and Si films which are suitable for multilayer device applications.
Requirements for utilization of CREB binding protein by hypersensitive site two of the beta-globin locus control region (2002)

Strong transactivation of the beta-globin genes is conferred by the beta-globin locus control region (LCR), which consists of four erythroid-specific DNase I hypersensitive sites (HS1-HS4). HS2 has a powerful enhancer activity dependent upon tandem binding sites for the erythroid cell- and megakaryocyte-specific transcription factor NF-E2. An important co-activator-mediating transactivation by HS2 is the histone acetyltransferase (HAT) CREB binding protein (CBP). We showed previously that recruitment of a GAL4-CBP fusion protein to HS2 largely bypassed the requirement of the NF-E2 sites for transactivation. To determine whether GAL4-CBP recruitment is sufficient for transactivation, we assessed the importance of cis-elements within HS2. Docking of GAL4-CBP upstream of an Agamma-globin promoter lacking HS2 only weakly activated the promoter, indicating that HS2 components are required for GAL4-CBP-mediated transactivation. Sequences upstream and downstream of the NF-E2 sites were required for maximal GAL4-CBP-mediated transactivation, and HAT catalytic activity of GAL4-CBP was critical. No single factor-binding site was required for GAL4-CBP-mediated transactivation. However, deletion of two sites, a CACC site and an E-box, abolished transactivation in transient and stable transfection assays. These results suggest that NF-E2 recruits CBP as a critical step in transactivation, but additional components of HS2 are required to achieve maximal enhancer activity.
The mechanism of the Mitsunobu esterification reaction. Part I. The involvement of phosphoranes and oxyphosphonium salts (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe mechanism of the Mitsunobu esterification reaction. Part I. The involvement of phosphoranes and oxyphosphonium saltsDavid Camp and Ian D. JenkinsCite this: J. Org. Chem. 1989, 54, 13, 3045–3049Publication Date (Print):June 1, 1989Publication History Published online1 May 2002Published inissue 1 June 1989https://pubs.acs.org/doi/10.1021/jo00274a016https://doi.org/10.1021/jo00274a016research-articleACS PublicationsRequest reuse permissionsArticle Views2662Altmetric-Citations77LEARN 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
IS6110 homologs are present in multiple copies in mycobacteria other than tuberculosis-causing mycobacteria (1997)

We have previously demonstrated homology between a 181-bp fragment of IS6110 and DNA from mycobacteria other than tuberculosis-causing mycobacteria (MOTT). Genomic DNA from 14 strains of MOTT was digested with PvuII and was hybridized with a probe derived from the 181-bp fragment and the INS1/INS2 international standard probe at high stringency. Multiple banding patterns were obtained from isolates of M. avium-M. intracellulare, M. fortuitum, M. kansasii, and M. malmoense. Differences in the banding patterns between and within species were obtained. This suggests that mycobacteria possess a family of IS3-like elements. The species of isolates suspected of being M. tuberculosis must be carefully determined before IS6110 restriction fragment length polymorphism analysis, and caution must be used in designing and evaluating diagnostic PCR tests based on this element.