gebhart/patrepeval huggingface dataset:
The Effect of [CuI]/[CuII] Ratio on the Kinetics and Conformation of Polyelectrolyte Brushes by Atom Transfer Radical Polymerization (2006)

Abstract Summary: The atom transfer radical polymerization of [2‐(methacryloyloxy)ethyl]trimethylammonium chloride (METAC) has been studied under different [Cu I ]/[Cu II ] ratios. The reaction kinetics is followed by ellipsometry and quartz crystal microbalance and it was found that the reaction speed influences the grafting density of the polymer brushes. High [Cu I ]/[Cu II ] ratios, i.e., fast polymerizations, lead to less dense polymer brushes. Plot of the frequency change of wet brushes on a QCM crystal (Δ f ) versus the dry thickness of brushes synthesized at different [Cu I ]/[Cu II ] ratios. image Plot of the frequency change of wet brushes on a QCM crystal (Δ f ) versus the dry thickness of brushes synthesized at different [Cu I ]/[Cu II ] ratios.
A Plant-Derived Recombinant Human Glucocerebrosidase Enzyme—A Preclinical and Phase I Investigation (2009)

Gaucher disease is a progressive lysosomal storage disorder caused by the deficiency of glucocerebrosidase leading to the dysfunction in multiple organ systems. Intravenous enzyme replacement is the accepted standard of treatment. In the current report, we evaluate the safety and pharmacokinetics of a novel human recombinant glucocerebrosidase enzyme expressed in transformed plant cells (prGCD), administered to primates and human subjects. Short term (28 days) and long term (9 months) repeated injections with a standard dose of 60 Units/kg and a high dose of 300 Units/kg were administered to monkeys (n = 4/sex/dose). Neither clinical drug-related adverse effects nor neutralizing antibodies were detected in the animals. In a phase I clinical trial, six healthy volunteers were treated by intravenous infusions with escalating single doses of prGCD. Doses of up to 60 Units/kg were administered at weekly intervals. prGCD infusions were very well tolerated. Anti-prGCD antibodies were not detected. The pharmacokinetic profile of the prGCD revealed a prolonged half-life compared to imiglucerase, the commercial enzyme that is manufactured in a costly mammalian cell system. These studies demonstrate the safety and lack of immunogenicity of prGCD. Following these encouraging results, a pivotal phase III clinical trial for prGCD was FDA approved and is currently ongoing.
Basic Concepts of Immune Response and Defense Development (2005)

The induction of immune responses requires critical interaction between innate parts of the immune system, which respond rapidly and in a relatively nonspecific manner, and other specific parts, which recognize particular epitopes on an antigen. A critical element in this interaction is the role played by dendritic cells (DCs), which represent "professional antigen-presenting cells." DCs endocytose and process antigen to peptide presented on the cell surface in association with major histocompatibility complex (MHC) molecules. This presentation results in interaction with and stimulation of helper T (Th) lymphocytes, which recognize peptide in association with either MHC class II or cytotoxic T (Tc) lymphocytes, which recognize peptide in association with MHC class I. Stimulation of Th lymphocytes produces the growth and differentiation factors (cytokines) essential for the B lymphocytes that have responded to a more intact form of the antigen and that differentiate into antibody-producing cells. The precise interaction between the cells depends on cognate ligand-receptor recognition between the B and Th lymphocytes. DCs also play a direct role with the stimulation of the B lymphocytes. It appears that DC can deliver antigen to the B lymphocytes in a more intact form than the processed form essential for stimulating T lymphocytes, and can release cytokines that assist the differentiation of the B lymphocytes into antibody-producing cells. This close relationship among the three cell types and the cytokines that are produced ensures the precise control and regulation necessary for immune response development.
The Effect of Nanoparticle-Enhanced Photoacoustic Stimulation on Multipotent Marrow Stromal Cells (2009)

In this article, we report a novel nanoparticle-enhanced biophysical technique that differentiates multipotent marrow stromal cells (MSCs) toward osteoblasts. We show that a brief (10 min) daily nanoparticle-facilitated exposure of MSCs to nanosecond pulse laser-induced photoacoustic (PA) stimulation enhances their differentiation toward osteoblasts. To observe osteodifferentiation under PA stimulation, tissue culture plates were seeded with MSCs without the osteogenic culture supplements (OS, 0.01 M beta-glycerophosphate, 50 mg/L ascorbic acid, 10(-8) M dexamethasone) in the presence and absence of single-walled carbon nanotubes (SWNTs) and gold nanoparticles (GNPs). The alkaline phosphatase activity, calcium content, and osteopontin secretion were monitored as indicators of MSCs' differentiation toward osteoblasts. The PA stimulated groups show up to 612% increase in calcium content compared to the controls cultured with osteogenic supplements (without PA stimulation) after 16 days. Among the PA stimulated groups, at day 16, MSCs incubated with SWNTs at 10 microg/mL concentrations showed up to 97% greater calcium content than those that did not contain SWNTs. The results demonstrated that PA stimulation not only promotes osteogenesis but also is synergistically enhanced by the presence of nanoparticles and, thus, has major implications for bone regeneration applications.
Retrospective Analysis on 1 900 Cases of Medical Malpractices. (2019)

Objective To study the change trend, distribution characteristics and causes of medical malpractices in 18 years, through retrospective analysis of 1 900 cases of medical malpractices, in order to provide guidance for the precaution and the treatment of medical malpractices. Methods A thousand and nine hundred medical malpractice cases that were accepted by Hunan Xiangya Judical Identification Center from 2000 to 2017 were collected. Statistical analysis on the caseloads, the clients, the department distributions, the levels of the hospital and the causes of medical malpractices, etc were conducted. Results The number of cases commissioned by third-party accreditation agencies for medical fault identification was on the rise; The clients of medical malpractices changed significantly in 18 years. Most of the medical malpractice cases occurred in secondary and tertiary hospitals, significantly more in surgery, obstetrics and gynecology. The occurrence of medical malpractices was related to the doctor's insufficient prediction of the severity of the disease and the possible complications, and failure to fully inform the relevant duty of care, etc. Conclusion China's medical malpractice solutions and medical fault identification procedures are gradually improving. Strengthening the medical malpractice precaution awareness of medical workers in surgery, obstetrics and gynecology will be conducive to resolution of medical malpractices.
Longitudinal mode control in GaAs lasers using a three-mirror active-passive cavity (1981)

Integrated optics techniques have been used to form a three-mirror laser diode configured to form a long active cavity and a short passive cavity. The third mirror results from an abrupt etched step down to the waveguide layer of a large optical cavity heterostructure laser. We have observed predominantly single-frequency operation at current levels up to 1.5 times threshold. For certain ratios of passive-to-active cavity length, these devices operated multimode within a narrow frequency range, whereas diodes with different length ratios emit two modes widely separated in frequency.
Antibody Responses and Infertility in Mice Following Oral Immunization with Attenuated Salmonella typhimurium Expressing Recombinant Murine ZP31 (1997)

Ovarian ZP3, the primary sperm receptor, is a major glycoprotein of mouse zona pellucida (ZP). Because antibodies raised against ZP3 block sperm-egg interaction, ZP3 has been considered a candidate immunogen in the development of a contraceptive vaccine. This study explored the possibility of using an attenuated Salmonella typhimurium vaccine strain expressing recombinant ZP3 to elicit an antibody response and infertility in mice. A cDNA sequence generated by the polymerase chain reaction encoding 342 amino acid residues (23-364) of the mouse (m)ZP3 was cloned into an Asd+ vector. An avirulent Salmonella vaccine strain stably expressed the ZP3 polypeptide and colonized the internal organs of mice after oral inoculation. Oral immunization of female BALB/c mice with the recombinant Salmonella vaccine strain expressing mZP3 induced significant levels of anti-native ZP IgG antibodies in serum and IgA antibodies in vaginal secretions. The IgG antibodies thus induced also bound to ZP in vivo. When mated with males, 3 of 6 females immunized with the recombinant Salmonella were infertile. In contrast, none of the mice that received Salmonella containing the vector plasmid produced antibodies to ZP and all were fertile. No ovarian inflammation was observed in the immunized mice at autopsy. The results suggest a potential oral contraceptive vaccine to control populations of rodent vectors of disease and to induce reversible infertility in humans.
Disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316,243). A potent .beta.-adrenergic agonist virtually specific for .beta.3 receptors. A promising antidiabetic and antiobesity agent (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleDisodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL 316,243). A potent .beta.-adrenergic agonist virtually specific for .beta.3 receptors. A promising antidiabetic and antiobesity agentJonathan D. Bloom, Minu D. Dutia, Bernard D. Johnson, Allan Wissner, Michael G. Burns, Elwood E. Largis, Jo Alene Dolan, and Thomas H. ClausCite this: J. Med. Chem. 1992, 35, 16, 3081–3084Publication Date (Print):August 1, 1992Publication History Published online1 May 2002Published inissue 1 August 1992https://pubs.acs.org/doi/10.1021/jm00094a025https://doi.org/10.1021/jm00094a025research-articleACS PublicationsRequest reuse permissionsArticle Views1576Altmetric-Citations238LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Biochemical Characterization and Cytochemical Localization of a Catecholamine-Sensitive Adenylate Cyclase in Isolated Capillary Endothelium (1972)

Capillaries were isolated from epididymal fat, and a catecholamine-sensitive adenylate cyclase found in these capillaries was characterized. The effect of various hormones on the accumulation of adenosine 3':5'-cyclic monophosphate in capillary endothelial cells was determined and the cyclase was found to exhibit mixed alpha and beta characteristics. Cyclase was cytochemically localized in these endothelial cells with 5'-adenylyl-imidodiphosphate as a specific cyclase substrate and alloxan as a specific cyclase inhibitor. Lead imidodiphosphate was precipitated at or near the site of cyclase activity upon hydrolysis of 5'-adenylyl-imidodiphosphate by cyclase. This reaction product was observed primarily on the luminal surface of intact capillaries, in micropinocytic invaginations, in free vesicles within the cytoplasm, and in the intracellular junctions.
Sporadic Primary Hyperparathyroidism in Young Patients (1999)

It appears that 1 HPT in young patients presents as a more severe disease, in terms of symptoms, biochemistry, and extent of pathologic findings. Physicians should be aware that 1 HPT does occur in young persons in a nonfamilial setting and that it may be responsible for a wide spectrum of symptoms. As in the adult population, 1 HPT is safely and effectively treated with surgical intervention.
Knowledge‐based protein modelling and design (1988)

A systematic technique for protein modelling that is applicable to the design of drugs, peptide vaccines and novel proteins is described. Our approach is knowledge-based, depending on the structures of homologous or analogous proteins and more generally on a relational data base of protein three-dimensional structures. The procedure simultaneously aligns the known tertiary structures, selects fragments from the structurally conserved regions on the basis of sequence homology, aligns these with the 'average structure' or 'framework', builds on the loops selected from homologous proteins or a wider database, substitutes sidechains and energy minimises the resultant model. Applications to modelling an homologous structure, tissue plasminogen activator on the basis of another serine proteinase, and to modelling an analogous protein, HIV viral proteinase on the basis of aspartic proteinases, are described. The converse problem of ab initio design is also addressed: this involves the selection of an amino acid sequence to give a particular tertiary structure, in this case a symmetrical domain of two Greek-key motifs.
Electrical and Mechanical Ventricular Activation During Left Bundle Branch Block and Resynchronization (2012)

Cardiac resynchronization therapy (CRT) aims to treat selected heart failure patients suffering from conduction abnormalities with left bundle branch block (LBBB) as the culprit disease. LBBB remained largely underinvestigated until it became apparent that the amount of response to CRT was heterogeneous and that the therapy and underlying pathology were thus incompletely understood. In this review, current knowledge concerning activation in LBBB and during biventricular pacing will be explored and applied to current CRT practice, highlighting novel ways to better measure and treat the electrical substrate.
A poliovirus replicon containing the chloramphenicol acetyltransferase gene can be used to study the replication and encapsidation of poliovirus RNA (1992)

A poliovirus replicon, FLC/REP, which incorporates the reporter gene chloramphenicol acetyltransferase (CAT) in place of the region encoding the capsid proteins VP4, VP2, and part of VP3 in the genome of poliovirus type 3, has been constructed. Transfection of cells indicates that the FLC/REP replicon replicates efficiently and that active CAT enzyme is produced as a CAT-VP3 fusion protein. The level of CAT activity in transfected cells broadly reflects the level of FLC/REP RNA. A series of mutations in the 5' noncoding region of poliovirus type 3 were introduced into FLC/REP, and their effects were monitored by a simple CAT assay. These experiments helped to define further the stem-loop structures in the 5' noncoding region which are essential for RNA replication. The CAT-containing poliovirus replicon could also be packaged into poliovirus capsids provided by helper virus and was stable as a subpopulation of virus particles over at least four passages. The location of the CAT gene in FLC/REP excluded the presence of an encapsidation signal in the region of the poliovirus genome comprising nucleotides 756 to 1805.
Undersulfated, low-molecular-weight glycol-split heparin as an antiangiogenic VEGF antagonist (2004)

Vascular endothelial growth factor (VEGF) represents a target for antiangiogenic therapies in a wide spectrum of diseases, including cancer. As a novel strategy to generate nonanticoagulant antiangiogenic substances exploiting binding to VEGF while preventing receptor engagement, we assessed the VEGF-antagonist activity of a low-molecular-weight (LMW) compound (ST2184, Mw = 5800) generated by depolymerization of an undersulfated glycol-split heparin derivative. The parental compound was obtained by introducing regular sulfation gaps along the prevalently N-sulfated heparin regions, followed by glycol-splitting of all nonsulfated uronic acid residues (approximately 50% of total uronic acid residues). ST2184 was endowed with a negligible anticoagulant activity after S.C. injection in mice. ST2184 binds VEGF165 as evaluated by its capacity to retard 125I-VEGF165 electrophoretic migration in a gel mobility shift assay and to prevent VEGF165 interaction with heparin immobilized onto a BIAcore sensor chip. Unlike heparin, ST2184 was unable to present 125I-VEGF165 to its high-affinity receptors in endothelial cells and inhibited VEGF165-induced neovascularization in the chick embryo chorioallantoic membrane. Undersulfated, LMW glycol-split heparins may therefore provide the basis for the design of novel nonanticoagulant angiostatic compounds.
Distinct Wnt signaling pathways have opposing roles in appendage regeneration (2006)

In contrast to mammals, lower vertebrates have a remarkable capacity to regenerate complex structures damaged by injury or disease. This process, termed epimorphic regeneration, involves progenitor cells created through the reprogramming of differentiated cells or through the activation of resident stem cells. Wnt/beta-catenin signaling regulates progenitor cell fate and proliferation during embryonic development and stem cell function in adults, but its functional involvement in epimorphic regeneration has not been addressed. Using transgenic fish lines, we show that Wnt/beta-catenin signaling is activated in the regenerating zebrafish tail fin and is required for formation and subsequent proliferation of the progenitor cells of the blastema. Wnt/beta-catenin signaling appears to act upstream of FGF signaling, which has recently been found to be essential for fin regeneration. Intriguingly, increased Wnt/beta-catenin signaling is sufficient to augment regeneration, as tail fins regenerate faster in fish heterozygous for a loss-of-function mutation in axin1, a negative regulator of the pathway. Likewise, activation of Wnt/beta-catenin signaling by overexpression of wnt8 increases proliferation of progenitor cells in the regenerating fin. By contrast, overexpression of wnt5b (pipetail) reduces expression of Wnt/beta-catenin target genes, impairs proliferation of progenitors and inhibits fin regeneration. Importantly, fin regeneration is accelerated in wnt5b mutant fish. These data suggest that Wnt/beta-catenin signaling promotes regeneration, whereas a distinct pathway activated by wnt5b acts in a negative-feedback loop to limit regeneration.
Potent and Selective Agonists of Human Melanocortin Receptor 5:  Cyclic Analogues of α-Melanocyte-Stimulating Hormone (2007)

The physiological role of melanocortin receptor 5 (MC5R) in humans is not clear despite its broad presence in various peripheral sites and in the brain, cortex, and cerebellum. To differentiate between functions of this receptor and those of the other melanocortin receptors (hMC1,3,4R), peptides with improved receptor subtype selectivity are needed. The endogenous ligands, melanocortins, and their various synthetic analogues are not particularly selective for hMC5R. In this study, cyclic peptides derived from MTII, Ac-Nle-cyclo(Asp-His6-D-Phe7-Arg8-Trp-Lys)-NH2 (a pan-agonist at the melanocortin receptors) were prepared and tested in binding and functional assays on CHO cells expressing hMC1b,3-5R. The analogues included in their structures sterically constrained hydrophobic amino acids in positions 6 (His) and 8 (Arg), and the D-4,4'-biphenyl residue in position 7 (D-Phe). Several of the new compounds were selective potent agonists at hMC5R. They are exemplified by peptide 29, Ac-Nle-cyclo(Asp-Oic6-D-4,4'-Bip7-Pip8-Trp-Lys)-NH2 (Oic=octahydroindole-2-COOH; 4,4'-Bip=4,4'-biphenylalanine; Pip=pipecolic acid) of IC50=0.95 nM and EC50=0.99 nM at hMC5R and selectivity for this receptor with respect to the other melanocortin receptors greater than 5000-fold.
Behaviour of Some Activated Nitriles Toward Barbituric Acid, Thiobarbituric Acid and 3-Methyl-1-Phenylpyrazol-5-one (2000)

The effect of some active methylene containing heterocyclic compounds, namely barbituric acid, thiobarbituric acid and 3-methyl-1-phenylpyrazol-5-one on a-cyano-3,4,5-trimethoxycinnamonitrile and ethyl a-cyano-3,4,5-trimethoxycinnamate (1a,b) was investigated. The structure of the new products was substantiated by their IR,1H-NMR and mass spectra.
Tunable Assembly of Protein‐Microdomains in Living Vertebrate Embryos (2018)

Subcellular events such as trafficking and signaling are regulated by self-assembled protein complexes inside the cell. The ability to rapidly and reversibly manipulate these protein complexes would likely enhance studies of their mechanisms and their roles in biological function and disease manifestation.<sup>[1, 2]</sup> This manuscript reports that thermally-responsive elastin-like polypeptides (ELPs) linked to fluorescent proteins can regulate the self-assembly and disassembly of protein microdomains within the individual cells of zebrafish embryos. By exploring a library of fluorescent ELP proteins, this reports demonstrates that ELPs can co-assemble different fluorescent proteins inside of embryos. By tuning ELP length and sequence, fluorescent protein microdomains can be assembled at different temperatures, in varying sizes, or for desired periods of time. For the first time in a multicellular living embryo, these studies demonstrate that temperature-mediated ELP assembly can reversibly manipulate assembly of subcellular protein complexes, which may have applications in the study and manipulation of <i>in vivo</i> biological functions.
Effect on anal pressure of percutaneous posterior tibial nerve stimulation for faecal incontinence (2014)

Percutaneous PTNS was effective in over 70% of patients in the present study with improvements in urgency, anal pressures and Wexner score.
Vascular anticoagulant β: a novel human Ca2+/phospholipid binding protein that inhibits coagulation and phospholipase A2 activity (1989)

A cDNA was cloned coding for a new member of the human Ca2+-modulated phospholipid-binding protein family termed annexins. Due to its 56% identity to the human vascular anticoagulant (VAC) the new protein is named VAC-beta, renaming the previous VAC as VAC-alpha. Northern analysis detects one hybridizing mRNA species of 2.2 kb in human placenta. Genomic Southern blot analysis shows a VAC-beta gene of comparable complexity to the VAC-alpha gene. The cDNA was expressed in Escherichia coli and the recombinant protein purified to homogeneity. Antiserum raised against VAC-beta weakly cross-reacts with VAC-alpha. The properties of VAC-beta as an anticoagulant and as an inhibitor of phospholipase A2 activity were analyzed and compared to those of VAC-alpha.
Nonalcoholic Fatty Liver Disease: A Pathological View (2012)

Reye's syndrome.
Hyperglycemic Crises in Adult Patients With Diabetes (2009)

PRECIPITATING FACTORS -The most common precipitating factor in the development of DKA and HHS is infection Other precipitating factors include discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and