gebhart/patrepeval huggingface dataset:
Antibody-drug conjugate model fast characterization by LC-MS following IdeS proteolytic digestion (2013)

Here we report the design and production of an antibody-fluorophore conjugate (AFC) as a non-toxic model of an antibody-drug conjugate (ADC). This AFC is based on the conjugation of dansyl sulfonamide ethyl amine (DSEA )-linker maleimide on interchain cysteines of trastuzumab used as a reference antibody. The resulting AFC was first characterized by routine analytical methods (SEC, SDS-PAGE, CE-SDS, HIC and native MS), resulting in similar chromatograms,electropherograms and mass spectra to those reported for hinge Cys-linked ADCs. IdeS digestion of the AFC was then performed, followed by reduction and analysis by liquid chromatography coupled to mass spectrometry analysis. Dye loading and distribution on light chain and Fd fragments were calculated, as well as the average dye to antibody ratio (DAR) for both monomeric and multimeric species. In addition, by analyzing the Fc fragment in the same run, full glycoprofiling and demonstration of the absence of additional conjugation was easily achieved. As for naked antibodies and Fc-fusion proteins, IdeS proteolytic digestion may rapidly become a reference analytical method at all stages of ADC discovery, preclinical and clinical development. The method can be routinely used for comparability assays, formulation, process scale-up and transfer, and to define critical quality attributes in a quality-by-design approach.
Plasma fibronectin promotes thrombus growth and stability in injured arterioles (2003)

Mice lacking both of the best-known platelet ligands, von Willebrand factor and fibrinogen, can still form occlusive thrombi in injured arterioles. The platelets of these animals accumulate excessive amounts of fibronectin (FN). These observations led us to examine the contribution of plasma FN (pFN) to thrombus formation. Inactivation of the FN gene in FN conditional knockout mice reduced pFN levels to <2% and platelet FN to approximately 20% of the levels in similarly treated control mice. The mice were then observed in a model of arterial injury to evaluate their capacity to form thrombi. The deficiency of pFN did not affect the initial platelet adhesion, but a delay of several minutes in thrombus formation was observed in the arterioles of pFN-deficient mice as compared with control mice. The thrombi that formed in the absence of pFN were stably anchored to the vessel wall but continuously shed platelets or small platelet clumps, thus slowing their growth significantly; the platelet/platelet cohesion was apparently diminished. Consequently the occlusion of pFN-deficient vessels was delayed, with the majority of vessels remaining patent at the end of the 40-min observation period. We conclude that, in addition to von Willebrand factor and fibrinogen, FN plays a significant role in thrombus initiation, growth, and stability at arterial shear rates and that deficiency in each of the three platelet ligands has its own specific impact on platelet plug formation.
Liposome Delivery Systems for Inhalation: A Critical Review Highlighting Formulation Issues and Anticancer Applications (2016)

This is a critical review on research conducted in the field of pulmonary delivery of liposomes. Issues relating to the mechanism of nebulisation and liposome composition were appraised and correlated with literature reports of liposome formulations used in clinical trials to understand the role of liposome size and composition on therapeutic outcome. A major highlight was liposome inhalation for the treatment of lung cancers. Many in vivo studies that explored the potential of liposomes as anticancer carrier systems were evaluated, including animal studies and clinical trials. Liposomes can entrap anticancer drugs and localise their action in the lung following pulmonary delivery. The safety of inhaled liposomes incorporating anticancer drugs depends on the anticancer agent used and the amount of drug delivered to the target cancer in the lung. The difficulty of efficient targeting of liposomal anticancer aerosols to the cancerous tissues within the lung may result in low doses reaching the target site. Overall, following the success of liposomes as inhalable carriers in the treatment of lung infections, it is expected that more focus from research and development will be given to designing inhalable liposome carriers for the treatment of other lung diseases, including pulmonary cancers. The successful development of anticancer liposomes for inhalation may depend on the future development of effective aerosolisation devices and better targeted liposomes to maximise the benefit of therapy and reduce the potential for local and systemic adverse effects.
Antibody responses to mumps virus proteins in natural mumps infection and after vaccination with live and inactivated mumps virus vaccines (1984)

Paired sera from 20 patients with acute mumps infection, 16 from persons vaccinated with live attenuated mumps virus vaccine, and 12 from persons vaccinated with formalin-inactivated virus vaccine were studied for mumps antibodies by single radial hemolysis (SRH), hemagglutination inhibition (HI), and by enzyme immunoassays (EIA) specific for whole virus, envelope glycoprotein, and nucleocapsid antibodies. Mumps patients had diagnostic rises in serum mumps antibodies in 90-100% of the cases depending on the method of assay. Vaccination resulted in seroconversion in 75-88% (live vaccine) and in 92% (inactivated vaccine) of the cases as detected by SRH or EIAs, whereas HI detected seroconversion only in 38% and 58% of the cases, respectively. Immunoprecipitation analyses revealed that all sera from mumps patients and nearly all postvaccination sera had antibodies against the main structural proteins of mumps virus. By immunoblotting, antibodies against denatured hemagglutinin-neuraminidase (HN) and fusion protein (F) were detected in 15-25% of mumps patients and persons vaccinated with live vaccine, whereas most postvaccination sera from those vaccinated with inactivated vaccine had HN (92%) and F (83%) protein antibodies, suggesting that antibodies against the denatured form of proteins are formed.
G-Protein binding domains of the angiotensin II AT1A receptors mapped with synthetic peptides selected from the receptor sequence (1998)

The vascular angiotensin II type 1 receptor (AT1AR) is a member of the G-protein-coupled receptor superfamily. We mapped the G-protein binding domains of the AT1AR using synthetic peptides selected from the receptor sequence, which interfere with AT1AR-G-protein coupling. Membrane GTPase activity was used as a measure of the functional coupling in rat vascular smooth muscle cells. Peptides corresponding to the N-terminal region of the second intracellular loop (residues 125-137), the N-terminal region of the third intracellular loop (217-227) and the juxtamembranous region of the C-terminal tail (304-316) inhibited angiotensin II-induced GTPase activation by 30%, 30%, and 70%, respectively. The latter two domains (217-227 and 304-316) are predicted to form amphiphilic alpha-helices. Only the peptide representing residues 217-227 stimulated basal activity (45%). No synthetic peptide had a significant effect on either the number or the affinity of the AT1AR binding. These observations indicate that domains of the second and third regions and the cytoplasmic tail of the AT1AR interact with G-proteins, and that multiple contacts with these receptor domains may be important for binding and activation of the G-proteins.
Microchip platforms for multiplex single-cell functional proteomics with applications to immunology and cancer research (2013)

Single-cell functional proteomics assays can connect genomic information to biological function through quantitative and multiplex protein measurements. Tools for single-cell proteomics have developed rapidly over the past 5 years and are providing approaches for directly elucidating phosphoprotein signaling networks in cancer cells or for capturing high-resolution snapshots of immune system function in patients with various disease conditions. We discuss advances in single-cell proteomics platforms, with an emphasis on microchip methods. These methods can provide a direct correlation of morphological, functional and molecular signatures at the single-cell level. We also provide examples of how those platforms are being applied to both fundamental biology and clinical studies, focusing on immune-system monitoring and phosphoprotein signaling networks in cancer.
Using a multiple storage quad tree on a hierarchical VLSI compaction scheme (1990)

A graph-generating algorithm and the experimental results of a hierarchical mask-layout-compaction scheme based on a plane-sweep algorithm, a fast region-query and a space-efficient data structure called the hierarchical multiple-storage quad tree are presented. For a mask-layout design, a rectangle is used as the primary element of the layout. Hence, in the hierarchical mask-compaction scheme, the graph-generating algorithm is based on the edges of rectangles rather than the central lines of symbols for the symbolic-compaction design. The plane-sweep algorithm is also called a dynamic event scheduling algorithm and can be applied to solve some other problems in the field of computational geometry and image processing. The efficiencies of the plane-sweep algorithm and the graph-generating algorithm are dependent on the region-query operations of the spatial data structure. By using the improved multiple storage quad tree as the spatial data structure in the system, the mask-layout compactor has been accomplished in a practically linear time performance in terms of the rectangles in the source layout.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Quantum Zeno Subspaces (2002)

The quantum Zeno effect is recast in terms of an adiabatic theorem when the measurement is described as the dynamical coupling to another quantum system that plays the role of apparatus. A few significant examples are proposed and their practical relevance discussed. We also focus on decoherence-free subspaces.
Furosemide-Sensitive Calcium Rise Induced by GABAA-Receptor Stimulation in Cultures of Embryonic Rat Striatal Neurons (1997)

Changes in [Ca2+]i induced by j–aminobutyric acid (GABA) were investigated in primary cultured neurons obtained from fetal rat striatum. GABA and muscimol induced [Ca2+]i rise, and bicucul-line blocked the effect of GABA. The [Ca2+]i elevating effect of GABA was also abolished by removal of extracellular Ca2+ or by application of nicardipine. Furthermore, furosemide, an inhibitor of Na+/K+/2Cl− co-transport, reversibly inhibited the GABA-induced [Ca2+], rise. These results suggest that due to the elevated level of intracellular Cl− maintained by Na+/K+/2Cl− transport activity in these neurons, opening of GABAA-receptor-associated Cl− channels results in Cl− efflux, leading to membrane depolarization and activation of L-type voltage-dependent Ca2+ channels.
Ten reasons why we should NOT use severity scores as entry criteria for clinical trials or in our treatment decisions* (2009)

We believe severity of illness scores are poor surrogates for risk stratification and should not be used as a criterion for patient enrollment into clinical trials or as the basis for individual treatment decisions.
[Poly(styryl)bipyridine]palladium(0)-catalyzed isomerization of quadricyclene (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT[Poly(styryl)bipyridine]palladium(0)-catalyzed isomerization of quadricycleneRoger J. Card and Douglas C. NeckersCite this: J. Org. Chem. 1978, 43, 15, 2958–2960Publication Date (Print):July 1, 1978Publication History Published online1 May 2002Published inissue 1 July 1978https://pubs.acs.org/doi/10.1021/jo00409a005https://doi.org/10.1021/jo00409a005research-articleACS PublicationsRequest reuse permissionsArticle Views86Altmetric-Citations34LEARN 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
CD44 is a physiological E-selectin ligand on neutrophils (2005)

The selectin family of adhesion molecules and their glycoconjugated ligands are essential for blood polymorphonuclear neutrophil (PMN) extravasation into inflammatory and infectious sites. However, E-selectin ligands on PMNs are not well characterized. We show here that CD44 immunopurified from G-CSF-differentiated 32D cells or from peripheral blood PMNs binds specifically to E-selectin. In contrast, CD44 extracted from bone marrow stromal or brain endothelial cell lines does not interact with E-selectin, suggesting cell-specific posttranslational modifications of CD44. PMN-derived CD44 binding activity is mediated by sialylated, alpha(1,3) fucosylated, N-linked glycans. CD44 enables slow leukocyte rolling on E-selectin expressed on inflamed endothelium in vivo and cooperates with P-selectin glycoprotein ligand-1 to recruit neutrophils into thioglycollate-induced peritonitis and staphylococcal enterotoxin A-injected skin pouch. CD44 extracted from human PMNs also binds to E-selectin. Moreover, we demonstrate that CD44 is hypofucosylated in PMNs from a patient with leukocyte adhesion deficiency type II, suggesting that it contributes to the syndrome. These findings thus suggest broader roles for CD44 in the innate immune response and uncover a potential new target for diseases in which selectins play a prominent role.
The Genetic Basis of Human Cytomegalovirus Resistance and Current Trends in Antiviral Resistance Analysis (2011)

Infections due to resistant human cytomegalovirus (CMV) are an emerging problem, particularly in immunocompromised hosts. When managing such patients, clinicians should be aware of the possibility of developing CMV antiviral resistance, especially while on prolonged therapy or if severe immunosuppression is present. CMV resistance to current antiviral agents is mediated by alterations in either the UL97 kinase or DNA polymerase, encoded by the UL97 and UL54 genes, respectively. UL97 mutations are capable of conferring resistance to ganciclovir, while UL54 mutations can impart resistance to ganciclovir, cidofovir, and foscarnet. If treatment failure is suspected to be due to antiviral resistance, CMV resistance analysis should be obtained. Phenotypic resistance assays performed on clinical isolates measure antiviral susceptibilities directly, but are laborious and time-consuming. Therefore, genotypic resistance analysis has become the more common means of diagnosing CMV resistance. Mutations in UL97 or UL54 may be clinically associated with resistance, but their effect on antiviral susceptibility must be confirmed by marker transfer techniques such as recombinant phenotyping.
Hepatocellular carcinoma: an overview (2001)

Hepatocellular carcinoma remains widely prevalent in tropical Africa and south-east Asia and is largely related to chronic hepatitis B virus (HBV) infection. Primary prevention by vaccination of infants at or near birth is effective but any reduction in tumour incidence cannot be expected for decades to come yet, even in those countries in which the necessary resources exist, as millions of adults remain chronically infected. Meanwhile, the incidence is rising in Japan, Mediterranean countries of Europe, Middle East and North Africa and in the USA, largely due to chronic hepatitis C virus (HCV) infection introduced by the indiscriminate use of unscreened blood and blood products in the recent past. Much has been learned from molecular biological studies on hepatocarcinogenesis incriminating the HBX gene of HBV, the core protein of HCV and a unique guanine to thymine transversion at codon 249 has been observed in cases due to aflatoxin exposure. The subject of precancerous lesions, notably adenomatous/dysplastic nodules and large-cell/small-cell change continues to be a source of much debate and the distinction of nodular lesions in cirrhosis from early carcinoma remains uncertain. Spontaneous regression of hepatocellular carcinoma is rare but it is probably immunologically mediated and treatment by activated T-lymphocytes may reduce recurrence rates after surgery. The positive identification of hepatocellular carcinoma by a liver-specific antibody has greatly facilitated the diagnosis in difficult cases.
Comparison of Recombinant Human Thrombin and Plasma-Derived Human α-Thrombin (2006)

Bleeding can be a serious complication of surgery, and topical thrombin is widely used as an adjunct to hemostasis in diverse surgical settings. The potent hemostatic properties of thrombin derive from its ability to activate platelets directly to aggregate and adhere to damaged vessels and to catalyze the formation simultaneously of a fibrin matrix. Application of exogenous thrombin bypasses the physiological process of generating a thrombin burst by directly initiating the terminal reactions of blood clot formation. Currently, thrombin used to control surgical bleeding is primarily from bovine plasma, with a small percentage from human plasma. Human thrombin isolated from pooled plasma carries the risk of transmitting plasma-borne pathogens or prion diseases. The bovine preparations have been associated with protein and preparative contaminants that pose potential risks of developing cross-reacting antibodies. There is a need for a pure therapeutic preparation of human thrombin. Recombinant human thrombin (rhThrombin) has been efficiently produced from a prethrombin-1 precursor obtained from Chinese hamster ovary cell culture. This rhThrombin is substantially free of process-derived contaminants and has been characterized extensively in terms of composition, primary, secondary, and tertiary structure, enzymatic activity; and in vivo pharmacology. In vivo studies of topically applied rhThrombin have shown it is effective in achieving hemostasis in a rabbit liver excisional wound model. Clinical studies are ongoing to evaluate the safety and efficacy of rhThrombin as an adjunct to hemostasis in patients undergoing surgery.
Does transplantation of cardiomyocytes improve function of infarcted myocardium? (1997)

These data suggest that transplantation of cardiomyocytes might be an effective means of improving function of infarcted myocardium.
Endocannabinoid Degradation, Endotoxic Shock and Inflammation (2002)

Endocannabinoids are an emerging class of lipid mediators, which include amides and esters of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) are the main endogenous agonists of cannabinoid receptors. Endotoxic shock is a potentially lethal failure of multiple organs that can be initiated by the inflammatory agent lipopolysaccharide (LPS), present in the outer membrane of gram-negative bacteria. LPS has been recently shown to stimulate the production of AEA in rat macrophages, and of 2-AG in rat platelets. The mechanism responsible for this effect has not been elucidated. On the other hand, mast cells are multifunctional bone marrow-derived cells found in mucosal and connective tissues and in the nervous system, where they play an essential role in inflammation. As yet, little is known about endogenous modulators and mechanisms of mast cell activation. Here, we review recent literature on the role of endocannabinoids in endotoxic shock and inflammation, and report our recent research on the effects of LPS on the production of AEA and 2-AG in human lymphocytes, and on AEA degradation by a specific AEA membrane transporter (AMT) and an AEA-degrading enzyme (fatty acid amide hydrolase, FAAH). We also report the ability of the HMC-1 human mast cells to degrade AEA through a nitric oxide-sensitive AMT and a FAAH. The role of endocannabinoids in HMC-1 degranulation is discussed as well. Taken together, it can be suggested that human lymphocytes and mast cells take part in regulating the peripheral endocannabinoid system, which can affect some activities of these cells.
Improvement of chemical stability of Li3PS4 glass electrolytes by adding MxOy (M = Fe, Zn, and Bi) nanoparticles (2013)

Sulfide glasses in the system Li2S–P2S5 are attractive as solid electrolytes for all-solid-state lithium batteries because of their high conductivity and high electrochemical stability. In the present study, we have focused on chemical stability in air of the sulfide glass electrolytes and succeeded in suppressing H2S generation by preparing composite electrolytes of the Li3PS4 glass and one of the metal oxides with the formula MxOy (MxOy: Fe2O3, ZnO and Bi2O3). The H2S amounts generated decreased in the order of the composite with Fe2O3, ZnO, and Bi2O3. It is noteworthy that the use of a favorable MxOy with a larger negative Gibbs energy change (ΔG) for the reaction with H2S is effective in improving the chemical stability of sulfide electrolytes. The composite electrolyte of 90Li3PS4·10ZnO (mol%) exhibited a relatively high ionic conductivity of over 10−4 S cm−1, negligible electronic conductivity and a wide electrochemical window over 5 V. The all-solid-state In/LiCoO2 cell using the 90Li3PS4·10ZnO composite electrolyte operated as a lithium secondary battery with excellent cycleability at room temperature.
Beneficial effect of aspirin in maintaining the patency of small-caliber prosthetic grafts after thrombolysis with urokinase or tissue-type plasminogen activator. (1986)

Despite successful thrombolysis of occluded prosthetic grafts, rethrombosis remains a problem. We investigated the efficacy of aspirin in maintaining patency of polytetrafluoroethylene grafts (3 mm X 3.5 cm) in canine femoral arteries after thrombolytic therapy. After induction of thrombosis, either tissue-type plasminogen activator (t-PA) or urokinase (UK) was infused just proximal to the thrombus (4000 U/min) until complete thrombolysis was achieved. Five of the 10 UK-treated dogs and five of the 10 t-PA-treated dogs received aspirin immediately after recanalization, and aspirin was continued (325 mg/day) for 4 weeks or until occlusion occurred. A systemic aspirin effect was confirmed by marked depression of serum thromboxane B2 and absent platelet aggregation. Only two of the 10 grafts in the aspirin-free group remained patent for 4 weeks. The remaining eight grafts had all reoccluded by 2 weeks. None of the 10 grafts in the aspirin-treated group reoccluded during the 4 weeks. This significantly improved patency (p less than .001) in the aspirin-treated group was observed equally in grafts treated with t-PA or UK. Thus aspirin is a potent agent in preventing rethrombosis after thrombolytic recanalization of prosthetic grafts.