gebhart/patrepeval huggingface dataset:
Inhibition of hepatitis B virus replication by targeted pretreatment of complexed antisense DNA in vitro (1996)

We have shown that antisense oligonucleotides can be targeted to hepatitis B virus (HBV)-infected cells, resulting in specific inhibition of viral protein synthesis and replication in vitro. The targeting system was based on the internalization of DNA complexes by highly selective receptors for galactose-terminal glycoproteins, asialoglycoproteins, on the surface of hepatocytes. Our objective in this study was to determine whether antisense DNA could be targeted to hepatocytes to prevent subsequent infection by HBV. A 21-mer phosphorothioate-linked oligo DNA complementary to the HBV polyadenylation signal and 5'-upstream sequences was complexed to a targetable DNA carrier consisting of asialoglycoprotein coupled to polylysine. Pretreatment of Huh7, asialoglycoprotein receptor (+) cells, with antisense complexes before lipofection with an HBV-plasmid at a level of 6.5 x 106 copies of plasmid per cell inhibited the amount of newly synthesized, core-associated viral DNA in Huh7 cells to undetectable levels, less than 0.1 pg, as assessed by quantitative polymerase chain reaction (PCR). Hepatitis B viral RNA transcripts were decreased by 60% compared with controls as detected by RNase protection assays, and HBV surface antigen (HBsAg) accumulation was inhibited by 97%. The inhibition lasted for 6 days and was dose dependent. Controls consisting of antisense alone and a random oligo complex showed no significant effect on any of the parameters under identical conditions. We conclude that preexposure of cells to targeted complexed antisense DNA can substantially block viral gene expression and viral replication after transfection of HBV DNA. (Hepatology 1996 Jun;23(6):1297-303)
Stereochemical Studies. VII. Thermal Rearrangement of α-Hydroxyimines to α-Aminoketones using optically Active Open Chain Compounds (1971)

Thermal rearrangements of three types of optically active open chain α-hydroxy-imines (I) were attempted. In all cases two optically active isomeric α-aminoketones (II) were obtained with almost full retention of optical activity, regardless of the species of the migrated groups in the 38-53% total yield. Stereospecifically, this thermal rearrangement was assumed to proceed via the intramolecular cyclic mechanism. The presence of a fragmentation reaction was shown. Thus, the coexistence of cleavage in all carbon-carbon bonds attached to the carbon atom bearing the hydroxy group was demonstrated for the first time. Preliminary experiments using racemic compounds were also described.
B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1 (2000)

TALL-1 is a recently identified member of the tumor necrosis factor (TNF) family that costimulates B lymphocyte proliferation. Here we show that B cell maturation protein (BCMA), a member of the TNF receptor family that is expressed only by B lymphocytes, specifically binds to TALL-1. A soluble receptor containing the extracellular domain of BCMA blocks the binding of TALL-1 to its receptor on the plasma membrane and inhibits TALL-1-triggered B lymphocyte costimulation. Overexpression of BCMA activates NF-kappaB, and this activation is potentiated by TALL-1. Moreover, BCMA-mediated NF-kappaB activation is inhibited by dominant negative mutants of TNF receptor-associated factor 5 (TRAF5), TRAF6, NF-kappaB-inducing kinase (NIK), and IkappaB kinase (IKK). These data indicate that BCMA is a receptor for TALL-1 and BCMA activates NF-kappaB through a TRAF5-, TRAF6-, NIK-, and IKK-dependent pathway. The identification of BCMA as a NF-kappaB-activating receptor for TALL-1 suggests molecular targets for drug development against certain immunodeficient or autoimmune diseases.
Plasmonics-A Route to Nanoscale Optical Devices (2001)

The further integration of optical devices will require the fabrication of waveguides for electromagnetic energy below the diffraction limit of light. We investigate the possibility of using arrays of closely spaced metal nanoparticles for this purpose. Coupling between adjacent particles sets up coupled plasmon modes that give rise to coherent propagation of energy along the array. A point dipole analysis predicts group velocities of energy transport that exceed 0.1c along straight arrays and shows that energy transmission and switching through chain networks such as corners (see Figure) and tee structures is possible at high efficiencies. Radiation losses into the far field are expected to be negligible due to the near-field nature of the coupling, and resistive heating leads to transmission losses of about 6 dB/μm for gold and silver particles. We analyze macroscopic analogues operating in the microwave regime consisting of closely spaced metal rods by experiments and full field electrodynamic simulations. The guiding structures show a high confinement of the electromagnetic energy and allow for highly variable geometries and switching. Also, we have fabricated gold nanoparticle arrays using electron beam lithography and atomic force microscopy manipulation. These plasmon waveguides and switches could be the smallest devices with optical functionality.
Esophageal Damage and Repair in GERD (2007)

Gastroesophageal reflux disease (GERD) encompasses all the signs and symptoms that result from the movement of highly acidic gastric contents into the esophagus, oropharynx, larynx, or lower airway. Given the close proximity to stomach, the esophagus is the easiest target, and particularly its mucosa which is lined by a moist stratified squamous epithelium. Damage to the squamous epithelium is typically heralded by the symptom of heartburn, and this symptom of GERD accompanied on endoscopy in one-third of subjects by visual evidence of tissue damage in the form of erosions—and in more advanced disease by ulceration, stricture, and/or Barrett specialized columnar epithelium. In the other two-thirds of subjects heartburn occurs in association with a normal-appearing esophagus on endoscopy. However, endoscopic biopsy reveals a variety of abnormalities, including mucosal infiltration with inflammatory cells, elongation of the rete pegs, squamous cell edema, basal cell hyperplasia, and a recently recognized lesion of squamous epithelium known as “dilated intercellular spaces.” Notably, dilated intercellular spaces in squamous epithelium are also identified in esophageal biopsies from subjects with erosive esophagitis and these lesions reversible upon treatment with proton pump inhibitors. These observations plus those from animal models in which the esophagus is damaged by acid perfusion suggest that dilated intercellular spaces are among the earliest lesions in GERD and reflect dysfunction of the apical junctional complexes within the epithelium. Further the data suggest that dilated intercellular spaces are both forerunner and promoter of such signs and symptoms of GERD as heartburn and erosions. As promoter of erosions, dilated intercellular spaces help make a case for there being a continuum between nonerosive and erosive forms of GERD, the latter reflecting either greater contact with luminal acidity or an inadequate reparative defense. Inhibition of normal reparative processes by persistent contact with noxious elements within the refluxate promotes aberrant repair in the form of peptic stricture and Barrett esophagus.
Thermodynamic Stabilization Mechanism of Block Copolymer Vesicles (2001)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTThermodynamic Stabilization Mechanism of Block Copolymer VesiclesLaibin Luo and Adi EisenbergView Author Information Department of Chemistry McGill University, 801 Sherbrooke Street West Montreal, Quebec, H3A 2K6, Canada Cite this: J. Am. Chem. Soc. 2001, 123, 5, 1012–1013Publication Date (Web):January 16, 2001Publication History Received24 November 2000Published online16 January 2001Published inissue 1 February 2001https://pubs.acs.org/doi/10.1021/ja005824vhttps://doi.org/10.1021/ja005824vrapid-communicationACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views2461Altmetric-Citations198LEARN 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 SUBJECTS:Copolymers,Hydrophilicity,Polymers,Quenching,Vesicles Get e-Alerts
Chronic critical limb ischemia: diagnosis, treatment and prognosis. (1999)

Chronic critical limb ischemia is manifested by pain at rest, nonhealing wounds and gangrene. Ischemic rest pain is typically described as a burning pain in the arch or distal foot that occurs while the patient is recumbent but is relieved when the patient returns to a position in which the feet are dependent. Objective hemodynamic parameters that support the diagnosis of critical limb ischemia include an ankle-brachial index of 0.4 or less, an ankle systolic pressure of 50 mm Hg or less, or a toe systolic pressure of 30 mm Hg or less. Intervention may include conservative therapy, revascularization or amputation. Progressive gangrene, rapidly enlarging wounds or continuous ischemic rest pain can signify a threat to the limb and suggest the need for revascularization in patients without prohibitive operative risks. Bypass grafts are usually required because of the multilevel and distal nature of the arterial narrowing in critical limb ischemia. Patients with diabetes are more likely than other patients to have distal disease that is less amenable to bypass grafting. Compared with amputation, revascularization is more cost-effective and is associated with better perioperative morbidity and mortality. Limb preservation should be the goal in most patients with critical limb ischemia.
Ctk: a protein-tyrosine kinase related to Csk that defines an enzyme family. (1994)

We used the polymerase chain reaction with degenerate oligonucleotide primers to search for Csk-related kinases. A cDNA coding for a Csk-like protein-tyrosine kinase was cloned from mouse brain and was designated ctk, for csk-type protein-tyrosine kinase. The 1.9-kb ctk mRNA was found to be expressed predominantly in brain and capable of encoding a 52-kDa protein-tyrosine kinase. The amino acid sequence of Ctk was found to possess 53% identity with mouse Csk, shared all the predicted structural features of Csk, and was capable of phosphorylating the carboxyl-terminal conserved tyrosine of Src family members. Our results thereby indicate that ctk represents a gene that defines a family of structurally and functionally related Csk-like protein-tyrosine kinases.
Acute ischaemia of the leg following accidental intra-arterial injection of dissolved flunitrazepam tablets (2008)

Accidental intra-arterial injection of drugs is a sporadic complication in i.v. drug addicts. A 22-year-old drug-abuser injected flunitrazepam tablets dissolved in tap water into her left femoral artery and presented with clinical signs of acute ischaemia of the left leg. Severe rhabdomyolysis developed within 5 hours after the injection. Selective arterial catheter angiography showed an acute occlusion of the posterior tibial artery. Combination therapy with i.a. urokinase, i.a. prostaglandines and i.v. anticoagulation resulted in re-opening of the obstructed distal artery and complete cessation of symptoms.
Prostacyclin analogues: the next drug-eluting stent? (2007)

Recent concern over existing drug-eluting stents, for the treatment of myocardial ischaemia, has led to the development of approaches that seek to inhibit restenosis while promoting the recovery of a functional endothelium. Prostacyclin analogues may be worthy candidates for use within a drug-eluting stent by virtue of their wide profile of vasoprotective effects. This article reviews recent developments in this area, and in so doing, reveals the future challenges for the further development of this technology.
Use of tamoxifen for breast cancer: twenty-eight years later. (1995)

The use of tamoxifen has resulted in a substantial modification of breast cancer's natural history, particularly in postmenopausal women. Ongoing clinical trials will examine the effects of tamoxifen therapy on lipids, coagulation proteins, bone, and endometrium, and its effectiveness as an agent in the prevention of breast cancer.
Prodrug strategies in nasal drug delivery (2002)

Nasal delivery offers a promising alternative to parenteral delivery. Prodrug strategies are usually aimed at modifying the parent drug such that favourable physicochemical and biological properties for absorption are obtained. Modulation of the drug hydrophilicity/lipophilicity or linkage of a moiety that will target membrane transporters or receptors may lead to enhanced drug absorption. A sizeable number of prodrug patents awarded in the past few years signal a high commercial potential for this approach. Novel developments include prodrug synthesis for drug delivery to the CNS via the nasal route. Prodrug modification also holds promise for intranasal delivery of anticancer drugs.
Evaluation of peptide libraries: An iterative strategy to analyze the reactivity of peptide mixtures with antibodies (1992)

Peptide libraries corresponding to a presumed mixture of 50,625 tetrapeptides or 16,777,216 hexapeptides were each prepared in a single assembly by standard solid-phase peptide synthesis. By enzyme-linked immunosorbent assay, the tetrapeptide library was shown to inhibit the binding of an antiserum to FMRF amide with an FLRF capture antigen; the hexapeptide library was shown to inhibit the binding of a monoclonal antibody to a 28 amino acid peptide with the corresponding peptide capture antigen. An iterative strategy of variation was used to determine for each position in the tetra- or hexapeptides which amino acid contributed the most to activity. As a result we were able to logically select out of the tetrapeptide library the sequence FLRF and to select out of the hexapeptide library a sequence that differed from the apparent probable epitope but was twice as active. A single amino acid substitution in the logically derived sequence gave a peptide that was 35 times as active as the hexapeptide sequence in the original 28 amino acid peptide.
Symptoms of Depression in People with Learning Disabilities (2002)

Depression is increasingly being recognized as an important cause of morbidity in learning disabilities, with particularly high levels in those previously thought to have had challenging behaviour. The problems of making a diagnosis in this population, however, are well known. One of the main issues is the atypical presentation of the disorder. The aim of this study is to assess the knowledge of a wide range of professionals involved in the care of people with learning disabilities. Overall, the results were encouraging, showing a relatively high baseline level of knowledge about depression, and an enthusiasm for further training.
[Apoptosis of multiple myeloma cells induced by 8-Cl-cAMP in vitro]. (2007)

The study was aimed to investigate the possible effects of 8-chloroadenosine 3', 5'-monophosphate (8-Cl-cAMP) on the multiple myeloma cells. The multiple myeloma cell line RPMI8226 was used as in vitro models. The effect on growth inhibition of RPMI8226 cells was evaluated by cell growth and viability curve. DNA fragment was visualized by agarose gel electrophoresis. The amount of apoptosis cells was measured by flow cytometry. Meanwhile Western blot assay were used to detect the change of several key cell cycle regulatory proteins CDK2 and cyclin E in these cells before and after the treatment. The results showed that low dose 8-Cl-cAMP (1-30 micromol/L) inhibited the proliferation and viability of RPMI8226 cells significantly. Agarose gel electrophoresis of DNA revealed the apoptosis characteristic "ladder" pattern. Apoptosis was also confirmed by flow cytometry. In addition, 8-Cl-cAMP was able to inhibit the cell growth through modulating expression of cell cycle regulators CDK2 and cyclin E. It is concluded that 8-cl-cAMP inhibits the proliferation and induce apoptosis of multiple myeloma cells effectively.
De novo synthesis of pyrimidine nucleotides by Helicobacter pylori (1994)

The incorporation of pyrimidine nucleotide precursors into Helicobacter pylori and the activities of enzymes involved in their synthetic pathways were investigated by radioactive tracer analysis and 31P nuclear magnetic resonance spectroscopy. The bacterium was found to take up aspartate and bicarbonate and to incorporate carbon atoms from these precursors into its genomic DNA. Orotate, an intermediate of de novo pyrimidine biosynthesis, and uracil and uridine, precursors for pyrimidine pathways, were also incorporated by the micro-organism. Radiolabelled substrates were used to assess the activities of aspartate transcarbamoylase, orotate phosphoribosyltransferase, orotidylate decarboxylase, CTP synthetase, uracil phosphoribosyltransferase, thymidine kinase and deoxycytidine kinase in bacterial lysates. The study provided evidence for the presence in H. pylori of an operational de novo pathway, and a less active salvage pathway for the biosynthesis of pyrimidine nucleotides.
Synthetic Vaccines: The Role of Adjuvants in Immune Targeting (2003)

A clear understanding of the mechanism of function of immune stimulatory adjuvants, which commonly accompany vaccines, is beginning to emerge. Recent investigations have demonstrated that Toll-like receptors (TLRs) are the critical link between the innate and the adaptive immunity. This link, which is normally activated as a result of collaboration between adjuvants and TLRs in triggering adaptive immunity, has been a subject of several recent investigations. With the advent of well-defined synthetic small molecules, which are designed to either mimic the adjuvants or, as in many cases, to structurally represent pathogen associated molecular patterns, it is now possible to design reproducible experiments and to draw credible conclusions. An adjuvant alerts the host immune system through a mechanism similar to that of an infection by a pathogen, which involves interaction with a TLR followed by a lsqou;danger signal' to the immune system. Secretion of cytokines and regulation of the expression of co-stimulatory molecules induced by innate response shape the magnitude and quality of adaptive response. Synthetic vaccines containing specific epitopes to which immune responses are desired, are expected to be far superior in target specificity while the benefits may be long-lasting. The immune responses by therapeutic vaccines are generally adaptive in nature and such responses often require the participation of the components of innate immunity, most importantly the TLRs and their pathogen-associated binding compliments. Structurally well-defined synthetic molecules derived from lipid A, muramyl di-peptide (MDP), and CpG motifs from bacterial DNA offer a wide range of immune stimulants for the development of fully synthetic vaccines. Lipo-peptide and self-adjuvanted antigens, in combination with additional immune stimulatory adjuvants in liposome delivery system, may be important in vaccine design. Combinations of synthetic mimics of microbial products are known to display synergistic effects in stimulating the immune system. Either alone or in combination with chemotherapy, innate immune therapy using TLR ligands to stimulate the immune system may offer an alternate therapeutic approach against rapidly mutating viral infections-(HIV/AIDS), and cancers.
Purification and properties of NADP-dependent formate dehydrogenase from Clostridium thermoaceticum, a tungsten-selenium-iron protein. (1983)

NADP-dependent formate dehydrogenase (NADP+) (EC 1.2.1.43) from Clostridium thermoaceticum has been purified to a specific activity of about 1100 mumol min-1 mg-1 when assayed at 55 degrees C and pH 7.5. The enzyme is extremely oxygen-sensitive and 7.6 microM of O2 causes 50% inhibition of initial velocity under assay conditions. Purification was done in an atmosphere at 95% N2 and 5% H2 and by including azide, dithionite, and glycerol as stabilizing agents in all buffer solutions. The enzyme contains, in molar ratios, 2 tungsten, 2 selenium, 36 iron, and about 50 inorganic sulfur. It has a molecular weight of about 340,000 and consist of two each of two different subunits giving the composition alpha 2 beta 2. The molecular weight of the alpha-subunit is 96,000 and that of the beta-subunit is 76,000. The selenium resides in the two alpha-subunits. Tungsten is released from the protein on denaturation and may exist as a tungsten cofactor. The enzyme catalyzes a reduction of CO2 with NADPH at pH 7.5 and 55 degrees C and Keq at these conditions is (2.35 +/- 0.49) x 10(-2) if CO2 is considered the active species and (1.48 +/- 0.31) x 10(-3) if HCO3- is the active species.
Ultimate Tensile Properties of Segmented Polyurethane Elastomers: Factors Leading to Reduced Properties for Polyurethanes Based on Nonpolar Soft Segments (1986)

Abstract Factors that could explain the lower tensile properties of nonpolar soft-segment-based polyurethane block copolymers relative to those of conventional polyether or polyester polyurethanes have been examined. Many of the materials studied in the literature have suffered from the use of soft segments with poor functionality, which has led to low molecular weight, network defects, and an unfavorable amount of crosslinking. Additionally, most of the materials have been based on soft segments whose molecular weight appears to be too high to obtain optimum properties. Polyurethanes based on nonpolar soft segments are also likely to suffer from premature phase separation during polymerization leading to low molecular weight and compositional heterogeneity, especially if the reaction is done in bulk. The lower soft-segment glass-transition temperature of, in particular, the polydimethylsiloxane polyurethanes can also contribute to their lower tensile properties at room temperature. However, if differences in the soft-segment glass-transition temperatures are accounted for by comparing samples at equivalent values of T−T g and other parameters are optimized, it appears that only a lack of soft-segment crystallizability under strain and possibly an excessively high degree of phase separation are inherently limiting the tensile properties of nonpolar soft-segment-based polyurethane block copolymers. The limited amount of available information concerning the effects of many of these factors suggests a need for additional work in this area.
Tympanoplasty With Calcium Phosphate (1984)

In 35 patients, with an average follow-up period of 2 1/2 years, the middle ear was reconstructed with prostheses of hydroxyapatite, which is the main substance of living bone tissue. In case of a missing incus, an interposition prosthesis of dense hydroxyapatite was used. Defects in the bony posterior canal wall were reconstructed with a canal wall prosthesis of porous hydroxyapatite and cavities with a barefoot plate were reconstructed with a total alloplastic middle-ear implant, consisting of a canal wall of porous hydroxyapatite and a chain of wire and dense hydroxyapatite. With these prostheses, radical surgery of the middle ear can be combined with a physiological reconstruction.