gebhart/patrepeval huggingface dataset:
Potent Adjuvanticity of a Pure TLR7-Agonistic Imidazoquinoline Dendrimer (2012)

Engagement of toll-like receptors (TLRs) serve to link innate immune responses with adaptive immunity and can be exploited as powerful vaccine adjuvants for eliciting both primary and anamnestic immune responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine responses. We synthesized a dendrimeric molecule bearing six units of a potent TLR7/TLR8 dual-agonistic imidazoquinoline to explore if multimerization of TLR7/8 would result in altered activity profiles. A complete loss of TLR8-stimulatory activity with selective retention of the TLR7-agonistic activity was observed in the dendrimer. This was reflected by a complete absence of TLR8-driven proinflammatory cytokine and interferon (IFN)-γ induction in human PBMCs, with preservation of TLR7-driven IFN-α induction. The dendrimer was found to be superior to the imidazoquinoline monomer in inducing high titers of high-affinity antibodies to bovine α-lactalbumin. Additionally, epitope mapping experiments showed that the dendrimer induced immunoreactivity to more contiguous peptide epitopes along the amino acid sequence of the model antigen.
[The effect of chronic UVB-irradiation on the growth, development and productivity of fodder beet]. (1992)

In a field study in 1989, the effect of additional UV-B-irradiation (with an intensity of 0.34, 0.49 or 0.77 W/m2, daily exposure of 17.3, 26.7 or 39.1 kJ/m2, and total exposure of 1457.3, 2248.8 or 3285.6 kJ/m2) on the growth, development and productivity of fodder beet var. Eckendorf yellow was investigated. The three levels of irradiation caused a delay of plant growth and a significant reduction of plant height (18-26%), air-dry weight of leaves (32-43%), wet weight of leaves (48-52%), and weight of root-crops (48-50%).
5-Chloro-N-(4-methoxy-3-piperazin-1-yl- phenyl)-3-methyl-2-benzothiophenesulfon- amide (SB-271046):  A Potent, Selective, and Orally Bioavailable 5-HT6 Receptor Antagonist (1999)

ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXT5-Chloro-N-(4-methoxy-3-piperazin-1-yl- phenyl)-3-methyl-2-benzothiophenesulfon- amide (SB-271046): A Potent, Selective, and Orally Bioavailable 5-HT6 Receptor AntagonistSteven M. Bromidge, Anthony M. Brown, Stephen E. Clarke, Kathy Dodgson, Tracey Gager, Helen L. Grassam, Phil M. Jeffrey, Graham F. Joiner, Frank D. King, Derek N. Middlemiss, Stephen F. Moss, Helen Newman, Graham Riley, Carol Routledge, and Paul WymanView Author Information Departments of Medicinal Chemistry, Neuroscience Research, and Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, Discovery Research, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, England Cite this: J. Med. Chem. 1999, 42, 2, 202–205Publication Date (Web):January 5, 1999Publication History Received21 September 1998Published online5 January 1999Published inissue 1 January 1999https://doi.org/10.1021/jm980532eCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views1124Altmetric-Citations153LEARN 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 InReddit Read OnlinePDF (82 KB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Antagonists,Central nervous system,Peptides and proteins,Receptors,Rodent models Get e-Alerts
Stable Superhydrophobic Coatings from Polyelectrolyte Multilayers (2004)

The present study demonstrates that the superhydrophobic behavior of the lotus leaf structure can be mimicked by creating a honeycomb-like polyelectrolyte multilayer surface overcoated with silica nanoparticles. Superhydrophobicity was achieved by coating this highly textured multilayer surface with a semifluorinated silane. The surface maintains its superhydrophobic character even after extended immersion in water. The key structural elements needed to create stable, superhydrophobic coatings from polyelectrolyte multilayers are discussed.
Determination of Phenols, Flavones, and Lignans in Virgin Olive Oils by Solid-Phase Extraction and High-Performance Liquid Chromatography with Diode Array Ultraviolet Detection (2001)

A simple analytical method for the quantitative determination of phenols, flavones, and lignans in virgin olive oils was developed. The polar fraction was isolated from small amounts of oil sample (2.5 g) by solid-phase extraction (SPE) using diol-phase cartridges, and the extract was analyzed by reversed-phase HPLC coupled with diode array UV detection. Chromatographic separation of pinoresinol, cinnamic acid, and 1-acetoxypinoresinol was achieved. Repeatability (RSD < 6.5%), recovery (> 90%), and response factors for each identified component were determined. SPE on amino-phase cartridges was used for isolating acidic phenols and as an aid for phenol identification. For the first time, 2-(4-hydroxyphenyl)ethyl acetate was detected in olive oils. The aldehydic structure of the ligstroside aglycon was confirmed by NMR spectroscopy. The colorimetric determination of total o-diphenolic compounds by reaction with molybdate was consistent with their HPLC determination. Differences between results obtained by liquid-liquid extraction and SPE were not statistically significant.
Long-term pamidronate treatment of advanced multiple myeloma patients reduces skeletal events. Myeloma Aredia Study Group. (1998)

Long-term monthly infusions of pamidronate as an adjunct to chemotherapy are superior to chemotherapy alone in reducing skeletal events in stage III multiple myeloma patients, and may improve the survival of patients on salvage therapy.
Chlamydia pneumoniae strain TWAR antibody and angiographically demonstrated coronary artery disease. (1991)

A recent case-control study from Finland reported a strong association between high antibody titers to Chlamydia pneumoniae, strain TWAR, and both chronic coronary heart disease and acute myocardial infarction. The current case-control study investigated the relation between C. pneumoniae immunoglobulin G antibody titers and angiographically diagnosed coronary artery disease. Cases (n = 461) were angiography patients with at least one coronary artery lesion occupying at least 50% of the luminal diameter. Controls (n = 95) were angiography patients with no demonstrable coronary artery disease. After standardization for age and gender, the geometric mean antibody titer was higher for cases than for controls (30.0 versus 24.0, p = 0.04). The estimated risk of coronary artery disease, adjusted for age and gender, was greater among subjects with high (greater than or equal to 1:64) antibody titers than among subjects with low (less than or equal to 1:8) antibody titers (relative risk, 2.0; 95% confidence interval, 1.0-4.0). The risk associated with a high antibody titer was particularly great for coronary artery disease with five or more lesions (relative risk, 2.8; 95% confidence interval, 1.2-7.0). The results of this cross-sectional study support an association between infection with C. pneumoniae and coronary artery disease.
Defect Sites on TiO2(110). Detection by O2 Photodesorption (1997)

The TiO2(110) surface, prepared with different densities of anion vacancy defect sites, has been investigated by studies of O2 photodesorption at 105 K. Two separate O2 photodesorption processes, α1 and α2, are detected and are postulated to be due to the presence of two different types of defect sites produced by annealing the crystal in vacuum before O2 adsorption. The measured photodesorption cross sections for these two states are Qα1-O2 = (3.1 ± 0.2) × 10-16 cm2 and Qα2-O2 = (4.3 ± 0.3) × 10-17 cm2 for 3.96 ± 0.07 eV photons. Both O2 states photooxidize CO chemisorbed on the reduced TiO2(110) surface. While the yield of the CO2 photoproduct increases with increasing crystal annealing temperature (and increasing defect coverage), the yield of α1-O2 and α2-O2 passes through a maximum at an annealing temperature of ∼600 K.
Pancreatographic investigation of pancreatic duct system and pancreaticobiliary malformation (2008)

To clarify the anatomy of the pancreatic duct system and to investigate its embryology, we reviewed 256 pancreatograms with normal pancreatic head, 81 with pancreas divisum and 74 with pancreaticobiliary maljunction. Accessory pancreatograms were divided into two patterns. The long-type accessory pancreatic duct forms a straight line and joins the main pancreatic duct at the neck portion of the pancreas. The short-type accessory pancreatic duct joins the main pancreatic duct near its first inferior branch. The short-type accessory pancreatic duct is less likely to have a long inferior branch arising from the accessory pancreatic duct. The length of the accessory pancreatic duct from the orifice to the first long inferior branch was similar in the short- and long-type accessory pancreatic ducts. The first long inferior branch from the long-type accessory pancreatic duct passes though the main pancreatic duct near the origin of the inferior branch from the main pancreatic duct. Immunohistochemically, in the short-type accessory pancreatic duct, the main pancreatic duct between the junction with the short-type accessory pancreatic duct and the neck portion was located in the ventral pancreas. The long-type accessory pancreatic duct represents a continuation of the main duct of the dorsal pancreatic bud. The short-type accessory pancreatic duct is probably formed by the proximal main duct of the dorsal pancreatic bud and its long inferior branch.
Thymic stromal lymphopoietin (2010)

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine expressed in skin, gut, lungs, and thymus. TSLP signals via a TSLP receptor (TSLPR), a heterodimer of the IL-7 receptor alpha chain and the TSLPR chain. The TSLPR chain is closely related to the common receptor gamma chain that is expressed on a wide range of cell types in the adaptive and innate immune system. TSLP exerts a profound influence on the polarization of dendritic cells to drive T helper (Th) 2 cytokine production. TSLP also directly promotes T-cell proliferation in response to T-cell receptor activation and Th2 cytokine production and supports B-cell expansion and differentiation. TSLP further amplifies Th2 cytokine production by mast cells and natural killer T cells. These properties confer on TSLP a critical role in driving Th2-mediated inflammation. This role is supported by the finding that TSLP expression is upregulated in keratinocytes of atopic dermatitis skin lesions and in bronchial epithelial cells in asthma.
Listeria monocytogenes infects human endothelial cells by two distinct mechanisms (1995)

Infection of endothelial cells by bacteria may be an important component of the bacteria's ability to escape host defenses and cause disease. Listeria monocytogenes cause sepsis and central nervous system infection in domesticated animals and immunocompromised humans, suggesting that this bacterium interacts with endothelial cells in a significant fashion. The experiments presented here tested the hypothesis that L. monocytogenes can invade and replicate within human endothelial cells. We found that L. monocytogenes grows readily in umbilical vein endothelial cells and that its intracellular life cycle involves phagosomal escape, F-actin-based motility, and cell-to-cell spread. We found that L. monocytogenes invaded endothelial cells by cell-to-cell spread from adherent mononuclear phagocytes which were previously infected by this bacterium. Interestingly, L. monocytogenes mutants lacking the invasion protein, internalin, bound less well to endothelial cells than did wild-type bacteria in the absence, but not the presence, of serum, and their invasion of endothelial cells was diminished under both conditions. Thus, endothelial cell infection by L. monocytogenes can occur by two distinct mechanisms: direct bacterial invasion of the endothelial cells in an internalin-mediated fashion or cell-to-cell spread from adherent, infected mononuclear phagocytes. These data support the idea that endothelial cell infection by L. monocytogenes is an important event in the pathogenesis of listeriosis.
Molecular Layer Deposition of Organic and Hybrid Organic-Inorganic Films (2007)

Polymeric films can be grown by a sequential, self-limiting surface chemistry process known as molecular layer deposition (MLD) that is very similar to atomic layer deposition (ALD). The MLD reactants are typically monomers for step-wise condensation polymerization and can yield completely organic or hybrid organic-inorganic alloys. This study will illustrate the MLD of organic films with the growth of nylon 66 and poly(p-phenylene terephthalamide) [PPTA]. Hybrid organic-inorganic MLD will also be demonstrated using the growth of poly(aluminum ethylene glycol) [PAEG]. The nylon 66 and PPTA MLD and the PAEG MLD will be examined with in situ transmission Fourier transform infrared (FTIR) spectroscopy, in situ quartz crystal microbalance (QCM) and ex situ x-ray reflectivity (XRR) measurements. These investigations will reveal the self-limiting chemistry and linear growth expected for MLD processing.
Control of Drosophila wing and haltere development by the nuclear vestigial gene product. (1991)

The Dipteran flight appendages, the wings and halteres, develop from larval imaginal discs that also produce other sections of the second and third thoracic adult body segments. Loss of vestigial (vg) function in Drosophila selectively eliminates wing and haltere formation. Here, we show that vg expression is spatially restricted to the presumptive wing and haltere regions of these imaginal discs. An intronic regulatory element mediates this restriction and may elaborate upon cues that activate vg expression in the embryonic disc primordia. The nuclear vg protein lacks any recognized nucleic acid-binding motif but is comprised of two putative functional domains, one of which bears similarity to part of the Deformed homeotic protein and may mediate protein-protein interactions. These results suggest that vg is directly involved in determining which thoracic imaginal disc cells will form wings and halteres, perhaps by interacting with other nuclear regulatory proteins.
Cytokine Assay of the Epidural Space Lavage in Patients With Lumbar Intervertebral Disk Herniation and Radiculopathy (2006)

Although a novel approach, the current study was unable to identify the presence of a series of inflammatory peptides in the epidural lavage of patients with symptomatic radicular pain due to herniated disc disease. We recommend alternative experimental designs than the one we pursued for definitively identifying potential sources of pain generators.
Applications of Aptamers as Sensors (2009)

Aptamers are ligand-binding nucleic acids whose affinities and selectivities can rival those of antibodies. They have been adapted to analytical applications not only as alternatives to antibodies, but as unique reagents in their own right. In particular, aptamers can be readily site-specifically modified during chemical or enzymatic synthesis to incorporate particular reporters, linkers, or other moieties. Also, aptamer secondary structures can be engineered to undergo analyte-dependent conformational changes, which, in concert with the ability to specifically place chemical agents, opens up a wealth of possible signal transduction schemas, irrespective of whether the detection modality is optical, electrochemical, or mass based. Finally, because aptamers are nucleic acids, they are readily adapted to sequence- (and hence signal-) amplification methods. However, application of aptamers without a basic knowledge of their biochemistry or technical requirements can cause serious analytical difficulties.
Therapy with high-dose Interleukin-2 (HD IL-2) in metastatic melanoma and renal cell carcinoma following PD1 or PDL1 inhibition (2019)

In this retrospective analysis, HD IL-2 therapy displayed durable antitumor activity in mM and mRCC patients who progressed following treatment with PD-1 and PD-L1 inhibition. The toxicities were generally manageable and consistent with expectations from HD IL-2 but physicians should watch for immune related toxicities such as pneumonitis. This analysis supports the development of randomized prospective trials to assess the proper sequencing and combination of immune checkpoint blockade and cytokine therapy.
Staphylococcus aureus Sortase Transpeptidase SrtA:  Insight into the Kinetic Mechanism and Evidence for a Reverse Protonation Catalytic Mechanism (2005)

The Staphylococcus aureus transpeptidase SrtA catalyzes the covalent attachment of LPXTG-containing virulence and colonization-associated proteins to cell-wall peptidoglycan in Gram-positive bacteria. Recent structural characterizations of staphylococcal SrtA, and related transpeptidases SrtB from S. aureus and Bacillus anthracis, provide many details regarding the active site environment, yet raise questions with regard to the nature of catalysis and active site cysteine thiol activation. Here we re-evaluate the kinetic mechanism of SrtA and shed light on aspects of its catalytic mechanism. Using steady-state, pre-steady-state, bisubstrate kinetic studies, and high-resolution electrospray mass spectrometry, revised steady-state kinetic parameters and a ping-pong hydrolytic shunt kinetic mechanism were determined for recombinant SrtA. The pH dependencies of kinetic parameters k(cat)/K(m) and k(cat) for the substrate Abz-LPETG-Dap(Dnp)-NH(2) were bell-shaped with pK(a) values of 6.3 +/- 0.2 and 9.4 +/- 0.2 for k(cat) and 6.2 +/- 0.2 and 9.4 +/- 0.2 for k(cat)/K(m). Solvent isotope effect (SIE) measurements revealed inverse behavior, with a (D)2(O)k(cat) of 0.89 +/- 0.01 and a (D)2(O)(k(cat)/K(m)) of 0.57 +/- 0.03 reflecting an equilibrium SIE. In addition, SIE measurements strongly implicated Cys184 participation in the isotope-sensitive rate-determining chemical step when considered in conjunction with an inverse linear proton inventory for k(cat). Last, the pH dependence of SrtA inactivation by iodoacetamide revealed a single ionization for inactivation. These studies collectively provide compelling evidence for a reverse protonation mechanism where a small fraction (ca. 0.06%) of SrtA is competent for catalysis at physiological pH, yet is highly active with an estimated k(cat)/K(m) of >10(5) M(-)(1) s(-)(1).
Oocyte-specific gene expression: molecular characterization of a cDNA coding for ZP-3, the sperm receptor of the mouse zona pellucida. (1986)

The mouse zona pellucida genes are expressed uniquely during oogenesis and are developmentally regulated in the absence of cell division. Little is known about the mechanisms that control the expression of these germ-line-specific genes that play crucial roles in early mammalian development. We have constructed a lambda gt11 cDNA library from ovarian poly(A)+ mRNA and have isolated clones coding for ZP-3, the mouse sperm receptor. The identity of the clones was confirmed by comparing their DNA sequence with an amino acid sequence obtained from an isolated ZP-3 peptide. The ZP-3 gene is transcribed as a 1.7-kilobase poly(A) mRNA that is detected exclusively in ovarian tissue. This germ-line-specific expression is reflected in the observed hypomethylation of the ZP-3 locus in ovarian but not liver or brain DNAs. The ZP-3 gene is otherwise identically organized in somatic and germ-line DNA where it appears to be present as a low-copy-number or single-copy gene. Despite the fact that the mouse sperm receptor demonstrates species specificity, the ZP-3 cDNA cross-hybridized with DNA from a variety of mammalian species, including rat, rabbit, dog, pig, cow, and human.
The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial (2010)

Malignant ascites is a common manifestation of advanced cancers, and treatment options are limited. The trifunctional antibody catumaxomab (anti-epithelial cell-adhesion molecule x anti-CD3) represents a targeted immunotherapy for the intraperitoneal (i.p.) treatment of malignant ascites secondary to epithelial cancers. In this phase II/III trial (EudraCT 2004-000723-15; NCT00836654), cancer patients (n = 258) with recurrent symptomatic malignant ascites resistant to conventional chemotherapy were randomized to paracentesis plus catumaxomab (catumaxomab) or paracentesis alone (control) and stratified by cancer type (129 ovarian and 129 nonovarian). Catumaxomab was administered as an i.p. infusion on Days 0, 3, 7 and 10 at doses of 10, 20, 50 and 150 mug, respectively. The primary efficacy endpoint was puncture-free survival. Secondary efficacy parameters included time to next paracentesis, ascites signs and symptoms and overall survival (OS). Puncture-free survival was significantly longer in the catumaxomab group (median 46 days) than the control group (median 11 days) (hazard ratio = 0.254: p < 0.0001) as was median time to next paracentesis (77 versus 13 days; p < 0.0001). In addition, catumaxomab patients had fewer signs and symptoms of ascites than control patients. OS showed a positive trend for the catumaxomab group and, in a prospectively planned analysis, was significantly prolonged in patients with gastric cancer (n = 66; 71 versus 44 days; p = 0.0313). Although adverse events associated with catumaxomab were frequent, they were manageable, generally reversible and mainly related to its immunologic mode of action. Catumaxomab showed a clear clinical benefit in patients with malignant ascites secondary to epithelial cancers, especially gastric cancer, with an acceptable safety profile.
Estrogen modulation of osteoblastic cell-to-cell communication (1998)

Two osteoblastic cell populations, calvarial and marrow stromal cells, were exposed to estrogen derivatives in vitro. The hormonal effect was monitored by following intracellular Ca+2 levels [Ca+2]i and gap-junction communication. We measured fast changes in intracellular Ca+2 levels in response, of these cells, to the steroid hormones. The changes were dose dependent revealing maximal activity at 100 pM by 17-beta-Estradiol and 1 nM by estradiol-CMO. Additionally, the effect of estrogen, on functional coupling of the cells, was measured using fluorescence dye migration and counting the number of neighboring cells coupled by gap junctions. An uncoupling effect was demonstrated in response of these cells to estrogen treatment. The quick stereospecific effect was achieved in the presence of 17-beta-estradiol but not in the presence of 17-alpha-estradiol. These results suggest the involvement of plasma membrane receptors in addition to the already known nuclear receptors in transducing the hormone effects in the osteoblastic cells.