gebhart/patrepeval huggingface dataset:
Preparation and properties of poly(dimethyl siloxane)–colloidal silica/functionalized colloidal silica nanocomposites (2012)

Abstract Aqueous spherical colloidal silica (CS) particles with a diameter of 15 ± 5 nm were modified with three different types of monofunctional silane coupling agents to prepare functionalized colloidal silica (FCS) particles. The effects of the surface chemistry of the FCS were studied as a function of the CS/FCS loading in the poly(dimethyl siloxane) (PDMS) polymer. The prepared PDMS–CS/FCS composites were investigated for their physical properties both in the cured and uncured states. The extent of filler–filler and filler–polymer interactions was found to vary with the type of functionalizing agent used to treat the surface of the CS. The filler–filler interaction appeared to be predominant in the PDMS–CS composites, and improved filler–polymer interaction was indicated in the case of the PDMS–FCS composites. The composites containing CS treated with methyltrimethoxysilane exhibited relatively better optical and mechanical properties compared to the other PDMS–FCS composites. This study highlighted the importance of judiciously choosing functionalizing agents to achieve PDMS–FCS composites with predetermined optical and mechanical properties. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012
[METAPRINT: a metabolic fingerprint]. (2002)

METAPRINT, a metabolic fingerprint based on predicted metabolic pathways and corresponding potential metabolites, has been developed. Calculated drug-likeness parameters (logP and MW) have been added into METAPRINT to achieve metabolic discrimination among the members of a chemical library. The application of METAPRINT in the design of cassette dosing experiments is demonstrated on a library of alpha-1a antagonists. Cassette design was performed by maximizing the intracassette Euclidean distances between compounds in METAPRINT space, using Metropolis Monte Carlo simulated annealing. Calculated distances in METAPRINT space were in accordance with experimental data.
Counter-regulatory responses to postprandial hypoglycaemia in patients with post-bariatric hypoglycaemia vs surgical and non-surgical control individuals (2023)

ClinicalTrials.gov NCT04334161.
Pharmacological Inhibition of polysialyltransferase ST8SiaII Modulates Tumour Cell Migration (2013)

Polysialic acid (polySia), an α-2,8-glycosidically linked polymer of sialic acid, is a developmentally regulated post-translational modification predominantly found on NCAM (neuronal cell adhesion molecule). Whilst high levels are expressed during development, peripheral adult organs do not express polySia-NCAM. However, tumours of neural crest-origin re-express polySia-NCAM: its occurrence correlates with aggressive and invasive disease and poor clinical prognosis in different cancer types, notably including small cell lung cancer (SCLC), pancreatic cancer and neuroblastoma. In neuronal development, polySia-NCAM biosynthesis is catalysed by two polysialyltransferases, ST8SiaII and ST8SiaIV, but it is ST8SiaII that is the prominent enzyme in tumours. The aim of this study was to determine the effect of ST8SiaII inhibition by a small molecule on tumour cell migration, utilising cytidine monophosphate (CMP) as a tool compound. Using immunoblotting we showed that CMP reduced ST8iaII-mediated polysialylation of NCAM. Utilizing a novel HPLC-based assay to quantify polysialylation of a fluorescent acceptor (DMB-DP3), we demonstrated that CMP is a competitive inhibitor of ST8SiaII (K i = 10 µM). Importantly, we have shown that CMP causes a concentration-dependent reduction in tumour cell-surface polySia expression, with an absence of toxicity. When ST8SiaII-expressing tumour cells (SH-SY5Y and C6-STX) were evaluated in 2D cell migration assays, ST8SiaII inhibition led to significant reductions in migration, while CMP had no effect on cells not expressing ST8SiaII (DLD-1 and C6-WT). The study demonstrates for the first time that a polysialyltransferase inhibitor can modulate migration in ST8SiaII-expressing tumour cells. We conclude that ST8SiaII can be considered a druggable target with the potential for interfering with a critical mechanism in tumour cell dissemination in metastatic cancers.
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-N-methylpyridine-2-carboxamide (AZD5305): A PARP1–DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs (2021)

Poly-ADP-ribose-polymerase (PARP) inhibitors have achieved regulatory approval in oncology for homologous recombination repair deficient tumors including BRCA mutation. However, some have failed in combination with first-line chemotherapies, usually due to overlapping hematological toxicities. Currently approved PARP inhibitors lack selectivity for PARP1 over PARP2 and some other 16 PARP family members, and we hypothesized that this could contribute to toxicity. Recent literature has demonstrated that PARP1 inhibition and PARP1-DNA trapping are key for driving efficacy in a BRCA mutant background. Herein, we describe the structure- and property-based design of <b>25</b> (AZD5305), a potent and selective PARP1 inhibitor and PARP1-DNA trapper with excellent in vivo efficacy in a BRCA mutant HBCx-17 PDX model. Compound <b>25</b> is highly selective for PARP1 over other PARP family members, with good secondary pharmacology and physicochemical properties and excellent pharmacokinetics in preclinical species, with reduced effects on human bone marrow progenitor cells in vitro.
ChemInform Abstract: Free Radical‐Mediated Aryl Amination: Convergent Two‐ and Three‐Component Couplings to Chiral 2,3‐Disubstituted Indolines. (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Slow Receptor Dissociation Kinetics Differentiate Macitentan from Other Endothelin Receptor Antagonists in Pulmonary Arterial Smooth Muscle Cells (2012)

Two endothelin receptor antagonists (ERAs), bosentan and ambrisentan, are currently approved for the treatment of pulmonary arterial hypertension (PAH), a devastating disease involving an activated endothelin system and aberrant contraction and proliferation of pulmonary arterial smooth muscle cells (PASMC). The novel ERA macitentan has recently concluded testing in a Phase III morbidity/mortality clinical trial in PAH patients. Since the association and dissociation rates of G protein-coupled receptor antagonists can influence their pharmacological activity in vivo, we used human PASMC to characterize inhibitory potency and receptor inhibition kinetics of macitentan, ambrisentan and bosentan using calcium release and inositol-1-phosphate (IP(1)) assays. In calcium release assays macitentan, ambrisentan and bosentan were highly potent ERAs with K(b) values of 0.14 nM, 0.12 nM and 1.1 nM, respectively. Macitentan, but not ambrisentan and bosentan, displayed slow apparent receptor association kinetics as evidenced by increased antagonistic potency upon prolongation of antagonist pre-incubation times. In compound washout experiments, macitentan displayed a significantly lower receptor dissociation rate and longer receptor occupancy half-life (ROt(1/2)) compared to bosentan and ambrisentan (ROt(1/2):17 minutes versus 70 seconds and 40 seconds, respectively). Because of its lower dissociation rate macitentan behaved as an insurmountable antagonist in calcium release and IP(1) assays, and unlike bosentan and ambrisentan it blocked endothelin receptor activation across a wide range of endothelin-1 (ET-1) concentrations. However, prolongation of the ET-1 stimulation time beyond ROt(1/2) rendered macitentan a surmountable antagonist, revealing its competitive binding mode. Bosentan and ambrisentan behaved as surmountable antagonists irrespective of the assay duration and they lacked inhibitory activity at high ET-1 concentrations. Thus, macitentan is a competitive ERA with significantly slower receptor dissociation kinetics than the currently approved ERAs. Slow dissociation caused insurmountable antagonism in functional PASMC-based assays and this could contribute to an enhanced pharmacological activity of macitentan in ET-1-dependent pathologies.
Demonstration of an improved COP hybrid chemical/mechanical heat pump (1995)

The design and experimental performance of a unique hybrid chemical/mechanical heat pump with a demonstrated 20% improvement in COP{sub c} compared to traditional vapor compression systems is presented. Rather than employing a traditional refrigerant alone, this heat pump uses a mixture of liquid absorbent and refrigerant. A unique lubrication-free sliding-vane rotary two-phase compressor is also discussed. This design has already demonstrated the ability to provide performance which is superior to the current performance leader, namely the vapor compression cycle, and will allow the use of environmentally-safe BFC refrigerants. An experimental prototype heat pump was built using an innovative two-phase lubrication-free rotary compressor. This compressor uses self lubricating, low-friction vanes and effectively uses the absorbent liquid to provide sealing and improved compressor performance. The compressor also utilizes a bore geometry which is optimized for the thermodynamics of the two-phase compression process. This heat pump system is ideal for cooling applications in the fractional to 20 ton range and is ideal for residential, commercial, and industrial heat pumps and refrigerators, automotive air conditioners, and aerospace cooling applications. Another significant benefit of the design is that the chemical/mechanical heat pump is very similar to existing vapor compression designs and would require little, ifmore » any, special training to service and maintain the system.« less
Deglycosylation of cartilage proteoglycans and their T cell responses (1991)

Conference Article| November 01 1991 Deglycosylation of cartilage proteoglycans and their T cell responses STEPHEN LYNN; STEPHEN LYNN Search for other works by this author on: This Site PubMed Google Scholar PRETTA GULAB; PRETTA GULAB Search for other works by this author on: This Site PubMed Google Scholar JOHN A. GOODACRE; JOHN A. GOODACRE *Department of Physiology and Medicine (Rheumatology), University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH Search for other works by this author on: This Site PubMed Google Scholar SHIRLEY MIDDLETON; SHIRLEY MIDDLETON *Department of Physiology and Medicine (Rheumatology), University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne NE2 4HH Search for other works by this author on: This Site PubMed Google Scholar JEFFREY P. PEARSON JEFFREY P. PEARSON Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1991) 19 (4): 386S. https://doi.org/10.1042/bst019386s Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation STEPHEN LYNN, PRETTA GULAB, JOHN A. GOODACRE, SHIRLEY MIDDLETON, JEFFREY P. PEARSON; Deglycosylation of cartilage proteoglycans and their T cell responses. Biochem Soc Trans 1 November 1991; 19 (4): 386S. doi: https://doi.org/10.1042/bst019386s Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 1991 Biochemical Society1991 Article PDF first page preview Close Modal You do not currently have access to this content.
Prognostic Factors and Treatment Outcome in Non-Hodgkin's Lymphoma of Waldeyer's Ring (1997)

Prognostic factors and treatment outcome of 71 patients with non-Hodgkin's lymphoma of Waldeyer's ring were analyzed retrospectively. In univariate analyses, unfavorable prognosis was associated with primary disease in the base of the tongue, stage III-IV diseases, B-symptoms, high-grade histology, T-cell phenotype, elevated serum LDH levels, decreased peripheral blood lymphocyte counts, and negative response on delayed type hypersensitivity skin reactions. Multivariate analysis showed that stage III-IV and T-cell phenotype were significant independent risk factors for death. In stage I-II lymphomas, patients with unilateral large or bilateral cervical lymph node involvement had a poorer prognosis. In stage I-II lymphomas with intermediate or high-grade histology, patients who had received radiotherapy with MTCOP-P chemotherapy (pirarubicin, cyclophosphamide, vincristine, methotrexate with leucovorin rescue, peplomycin, and predonisolone) showed significantly better 5-year disease-free survival rate compared with patients treated with radiotherapy alone.
Fabrication of Metal Structures with Nanometer-Scale Lateral Dimensions by Sectioning Using a Microtome (2004)

This Communication describes the fabrication of planar structures comprising metallic features with nanometer-scale lateral dimensions in polymer prepared by sectioning a thin metallic film, embedded in a polymer matrix, in a plane perpendicular to the metallic film. This procedure converts a structure that is thin along the z-axis into a structure that is thin along the x-axis. The embedded thin metal film is still conductive and can be used as a nanoelectrode. The structure and composition of the exposed nanoedge can be easily tuned by changing the structure of the surface supporting the metal film, and the composition and the thickness of that film.
Geometrical E-beam proximity correction for raster scan systems (1999)

High pattern fidelity is a basic requirement for the generation of masks containing sub micro structures and for direct writing. Increasing needs mainly emerging from OPC at mask level and x-ray lithography require a correction of the e-beam proximity effect. The most part of e-beam writers are raster scan system. This paper describes a new method for geometrical pattern correction in order to provide a correction solution for e-beam system that are not able to apply variable doses.
Risk governance of potential emerging risks to drinking water quality: Analysing current practices (2018)

The presence of emerging contaminants in the aquatic environment may affect human health via exposure to drinking water. And, even if some of these emerging contaminants are not a threat to human health, their presence might still influence the public perception of drinking water quality. Over the last decades, much research has been done on emerging contaminants in the aquatic environment, most of which has focused on the identification of emerging contaminants and the characterisation of their toxic potential. However, only limited information is available on if, and how, scientific information is implemented in current policy approaches. The opportunities for science to contribute to the policy of emerging contaminants in drinking water have, therefore, not yet been identified. A comparative analysis was performed of current approaches to the risk governance of emerging chemical contaminants in drinking water (resources) to identify any areas for improvement. The policy approaches used in the Netherlands, Germany, Switzerland and the state of Minnesota were analysed using the International Risk Governance Council framework as a normative concept. Quality indicators for the analysis were selected based on recent literature. Information sources used were scientific literature, policy documents, and newspaper articles. Subsequently, suggestions for future research for proactive risk governance are given. Suggestions include the development of systematic analytical approaches to various information sources so that potential emerging contaminants to drinking water quality can be identified quickly. In addition, an investigation into the possibility and benefit of including the public concern about emerging contaminants into the risk governance process was encouraged.
A method for automatic generation of a fuzzy model (2002)

The goal of this research is to develop a method to automate the process of fuzzy model construction. The method we developed extends the existing methods and is based on a combination of genetic algorithms and statistic techniques. The preliminary testing shows that it has the advantages of implementation simplicity, a short training cycle and simple resulting fuzzy model.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
NANOTIPS COLD-END CONTACT FOR MICROCOOLING SYSTEMS (2005)

The paper presents the fabrication of nanotips cold-end contact for microcooling system. The fabrication process is based on an optimized isotropic plasma etching in SF 6 / O 2 using an ICP-deep RIE system from STS. We managed to fabricate the radius of the nanotips which are below 50 nm.
An experience of using Laennec in patients at high risk of a cytokine storm with COVID-19 and hyperferritinemia (2020)

The probability of formation of the so-called “cytokine storm” accompanied by an avalanche-like growth of inflammatory markers – interleukins (IL)-1β, -6, interferon-γ, tumor necrosis factor-α, C-reactive protein (CRP), ferritin, etc. is high at a heavy current of COVID-19. In the absence of adequate treatment in the development of “cytokine storm” increases the risk of death, especially against the background of comorbid pathology. Methods . In April-May 2020, patients ( n = 28: 12 men, 16 women; age 39 – 86 years) with long, chronic COVID-19 course were under observation, hospitalized on critical days of the disease. All patients reported anosmia, cough with poor sputum, signs of conjunctivitis. The patients had chronic diseases ( n = 22: coronary heart disease, diabetes mellitus type 2, scleroderma). All patients were given standard therapy; half ( n = 14) were additionally prescribed Laennec for 3 – 10 days (6 ml per 350 ml of 0.9% NaCl solution, intravenous infusion for the first 3 days, from day 4 – 6 ml per 250 ml of 0.9% NaCl solution) until stable remission is achieved. Results . The majority state ( n = 25) stabilized; several patients died in the control group ( n = 3; p = 0.067). In spite of the state stabilization, no reliable positive dynamics was noted in the control group for the tested parameters. Initially, liver dysfunction (level of alanine aminotransferase (ALT) – 113 ± 121, aspartate aminotransferase (AST) – 90.8 ± 87) was registered in 71% of patients, 8 units/l) and high risk of “cytokine storm” development (ferritin levels in men – 480 – 1 072 µg/l, in women – 274.7 – 493 µg/l, C-reactive protein – 5.0 – 52.6 mg/l, lymphocytes – &lt; 25%). Positive clinical dynamics, a decrease in the level of ferritin (–282 µg/l – in men, –80 µg/l – in women; p = 0.039), an increase in blood oxygenation to normal values ( p = 0.0029), a decrease in the area of lung injury according to CT data (on average – 10%); p = 0.0027), increase in relative lymphocyte content (+8%; p = 0.04), normalization of markers of liver dysfunction (AST, ALT), creatinine and systolic blood pressure ( p &lt; 0.05) were observed on prescription of Laennec. All patients who received Laennec recovered within 3 – 15 days from the start of the drug and were discharged with a negative test for SARS-CoV-2. Conclusion . Health condition is significantly improved, a wide range of hepatoprotective, immunomodulatory and regenerative effects are observed when the polypeptide Laennec is included in the complex therapy in patients with severe COVID-19. Laennec should be used primarily in patients with liver pathology, diabetes mellitus type 2, coronary heart disease, including high ferritin levels.
Aggrecan degradation in osteoarthritis and rheumatoid arthritis (1995)

Aggrecan turnover is critically important to maintain extracellular matrix homeostasis in articular cartilage. Cartilage aggrecan metabolism has been studied in chondrocyte cell cultures, cartilage explant cultures, and in whole animal models. In many of these studies, matrix metalloproteinases (MMPs) are proposed to degrade cartilage aggrecan. MMP expression appears elevated in joint tissues from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) (Dean et al. 1989, Wolfe et al. 1993) and inhibitors of both MMPs and thiol proteinases have been shown to block aggrecan (Buttle et al. 1992) and type II collagen (Mort et al. 1993) degradation in cartilage explant cultures. Using antibodies and cDNA probes, elevations in expression and concentration of many of these enzymes in animal models and in OA and RA have been described. Human cartilage aggrecan has now been cloned and sequenced (Doege et al. 1991). This information, in combination with the ability to sequence aggrecan and aggrecan fragments at the protein level, has resulted in the identification of several aggrecan fragments which appear to result from proteinase degradation. In this report, we describe data which suggest that MMPs may in part be responsible for aggrecan catabolism in normal articular cartilage, as well as in the elevated catabolism seen in OA and RA.
Corrosion of Silicon Nitride Ceramics in Aqueous Hydrogen Chloride Solutions (1988)

The leaching behavior of pressureless sintered and hotpressed Si 3 N 4 containing Y 2 O 3 , Al 2 O 3 , and AlN and hot isostatically pressed Si 3 N 4 without additives was studied in 0.1 M to 10 M HCl aqueous solutions at 50° to 100°C. Y and Al ions contained in the grain‐boundary phase dissolved in HCl solutions, but dissolution of the Si ion from the matrix was negligible. The dissolution of Y and Al ions in HCl solutions was adequately described by a surface‐chemical‐reaction‐controlled, shrinking‐core model in &lt;1 M HCl solutions and by a diffusion‐controlled, shrinking‐core model in &gt;5 M HCl solutions. The rates of dissolution of both Y and Al ions decreased as the degree of crystallinity of the grain‐boundary phase increased. The fracture strength of the corroded samples linearly decreased with increasing degree of dissolution of soluble Y and Al ions.
Inhibition of intestinal epithelial DNA synthesis and adaptive hyperplasia after jejunectomy in the rat by suppression of polyamine biosynthesis. (1984)

Transient increases in the activity of ornithine decarboxylase (ODC), the first and rate-limiting enzyme in polyamine biosynthesis, may be critical to initiation of cell growth. We previously reported such increases in ODC activity, and the polyamines, putrescine, and spermidine in rat ileal mucosa between days 1 and 4 after intestinal resection. During this time, there is initiation of mucosal cell hyperplasia, as measured morphologically and biochemically. Intestinal weight and mucosal thickness increase, as do mucosal DNA content and DNA synthesis. In the present study, we gave rats the specific irreversible ODC inhibitor, alpha-difluoromethyl ornithine (DFMO), beginning 3 d before jejunectomy. DFMO completely suppressed the increases in ODC activity and polyamine content in the intestinal mucosa. The suppression in ODC activity was associated with an 87% suppression of DNA synthesis, and resulted in a complete abolition of intestinal adaptation, as manifested by the absence of intestinal weight gain, increase in mucosal thickness, or increase in crypt cell production. Our results indicate that the increases in ODC activity and polyamine biosynthesis are critical for adaptive postresectional crypt cell proliferation in vivo, and that the critical step mediated by polyamines in this adaptive process is the onset of new DNA synthesis.