gebhart/patrepeval huggingface dataset:
Interactions of adenosine A1and A2areceptors on renal microvascular reactivity (2001)

Adenosine vasoconstricts preglomerular arterioles via adenosine A1 receptors. Because adenosine also activates adenosine A2 receptors, its overall renal vascular actions are complex and not fully understood. The present study was performed to determine the relative contributions of adenosine A1 and A2a receptors to the responsiveness of the renal microvasculature to adenosine. Afferent and efferent arteriolar diameters were monitored in vitro using the blood-perfused rat juxtamedullary nephron preparation. Basal afferent and efferent arteriolar diameters averaged 17.1 +/- 0.5 (n = 35) and 17.8 +/- 0.5 (n = 20) microm, respectively. Superfusion with 0.1 and 1 micromol/l adenosine did not significantly alter afferent and efferent arteriolar diameters; however, 10 micromol/l adenosine significantly reduced afferent and efferent arteriolar diameters (-8.2 +/- 0.8 and -5.7 +/- 0.6%, respectively). The afferent and efferent arteriolar vasoconstrictor responses to adenosine waned at a dose of 100 micromol/l, such that diameters returned to values not significantly different from control within 2 min. During adenosine A1 receptor blockade with 8-noradamantan-3-yl-1,3-dipropylxanthine (KW-3902: 10 micromol/l), 10 and 100 micromol/l adenosine significantly increased afferent diameter by, respectively, 8.1 +/- 1.2 and 13.7 +/- 1.3% (n = 14) and efferent arteriolar diameter by 6.4 +/- 1.3 and 9.3 +/- 1.2% (n = 8). The afferent and efferent arteriolar vasodilatory responses to adenosine in the presence of KW-3902 were significantly attenuated by addition of the adenosine A2a receptor antagonist 1,3-dipropyl-7-methyl-8-(3,4-dimethoxystyryl)xanthine (KF-17837: 15 micromol/l, n = 7 and 6, respectively). The addition of KF-17837 alone significantly enhanced afferent (n = 15) and efferent (n = 6) arteriolar vasoconstrictor responses to 1, 10, and 100 micromol/l adenosine. These results indicate the presence of adenosine A1 and A2a receptors on afferent and efferent arterioles of juxtamedullary nephrons, such that adenosine A2a receptor-mediated vasodilation partially buffers adenosine-induced vasoconstriction in both pre- and postglomerular segments of the renal microvasculature.
Klotho Depletion Contributes to Increased Inflammation in Kidney of the db/db Mouse Model of Diabetes via RelA (Serine)536 Phosphorylation (2011)

These findings suggest that Klotho serves as an anti-inflammatory modulator, negatively regulating the production of NF-κB-linked inflammatory proteins via a mechanism that involves phosphorylation of Ser(536) in the transactivation domain of RelA.
Multivalent Group A Streptococcal Vaccine Elicits Bactericidal Antibodies against Variant M Subtypes (2005)

Group A streptococci cause a wide spectrum of clinical illness. One of several strategies for vaccine prevention of these infections is based on the type-specific M protein epitopes. A multivalent M protein-based vaccine containing type-specific determinants from 26 different M serotypes is now in clinical trials. Recent epidemiologic studies have shown that, within some serotypes, the amino-terminal M protein sequence may show natural variation, giving rise to subtypes. This raises the possibility that vaccine-induced antibodies against the parent type may not be as effective in promoting bactericidal killing of variant subtypes. In the present study we used rabbit antisera against the 26-valent M protein-based vaccine in bactericidal tests against M1, M3, and M5 streptococci, which were represented by multiple subtypes. We show that the vaccine antibodies effectively promoted in vitro bactericidal activity despite the fact that the M proteins contained naturally occurring variant sequences in the regions corresponding to the vaccine sequence. Our results show that the variant M proteins generally do not result in significant differences in opsonization promoted by rabbit antisera raised against the 26-valent vaccine, suggesting that a multivalent M protein vaccine may not permit variant subtypes of group A streptococci to escape in a highly immunized population.
Vascular 5‐HT1‐like receptors mediating vasoconstriction and vasodilatation: their characterization and distribution in the intact canine cardiovascular system (1995)

1. In anaesthetized dogs, intra-left atrial administration of 5-hydroxytryptamine (5-HT) and selected tryptamine analogues (5-carboxamidotryptamine, 5-CT; 5-methyl tryptamine, 5-MT; alpha-methyl 5-hydroxytryptamine, alpha-HT; sumatriptan, Sum) in the presence of ketanserin and MDL72222 (5-HT2 and 5-HT3 receptor antagonists, respectively), produced dose-related changes in carotid, coronary and renal vascular conductance mediated by vascular 5-HT1-like receptors. 2. In the carotid vascular bed, 5-HT, 5-MT, alpha-HT and Sum were vasoconstrictors with a rank order of potency (comparing ED50 values) of 5-HT = Sum > 5-MT > alpha-HT. By contrast in this vascular bed, 5-CT was a potent vasodilator. 3. In the coronary vascular bed, 5-HT, 5-CT, 5-MT and alpha-HT were vasodilators with a rank order of potency (comparing ED50 values) of 5-CT > 5-HT > 5-MT > alpha-HT. In this vascular bed, Sum was without effect. 4. In the renal vascular bed, 5-HT, 5-CT, 5-MT, alpha-HT and Sum were vasoconstrictors with a rank order of potency (comparing ED50 values) of 5-CT > 5-HT > Sum > 5-MT > alpha-HT. 5. The coronary (and carotid) vasodilator responses to 5-CT were antagonized by the 5-HT1-like receptor antagonists, spiperone (1 mg kg-1) and methiothepin (0.1 mg kg-1), whereas the renal vasoconstrictor responses to this tryptamine analogue were antagonized only by methiothepin. 6. It is concluded from these studies that agonist finger-printing in vivo, using tryptamine analogues,identifies and confirms the functional presence of at least two pharmacologically distinct subtypes of the 5-HT1-like receptor in the intact canine cardiovascular system. These two subtypes are located on the vascular smooth muscle and mediate direct vasoconstriction and vasodilatation responses in vivo.7. In addition, these studies confirm that the distribution of these subtypes within the major vascular beds, shows a marked heterogeneity. The carotid vascular responses to the tryptamine analogue sindicate the presence of both the vasodilator and the vasoconstrictor subtypes. The coronary vascular responses to these analogues are, however, consistent with presence of the vasodilator subtype, only. By contrast, the renal vascular responses to these analogues indicates only the presence of the vasoconstrictor subtype.
Increased Coronary Events in Depressed Cardiovascular Patients: 5-HT2A Receptor as Missing Link? (2003)

Depression appears to be associated with an increased susceptibility for serotonin-mediated platelet activation. Upregulation and/or increased sensitivity of 5-HT2A/1B receptors and downregulated 5-HT transporter receptors in the periphery may contribute to increased risk of thromboembolic events in patients with depression and cardiovascular disease. Increased platelet reactivity based on a hyperreactive 5-HT2A receptor signaling system might be influenced by antidepressive medication that antagonizes platelet 5-HT2A receptors.
The Non-glycerol Process of Biodiesel Fuel Treated in Supercritical Methanol (2004)

Biodiesel fuel is a renewable fuel for diesel engine consisting of fatty acid methyl ester fromorganic oils and fats. In the conventional processes for production biodiesel fuel, glycerol is generallyproduced as a by-product. But, utilization of this by-product for other application is very hard, sincevarious impurities are mixed. Therefore, we developed new process that does not generate glycerol. Thisprocess is simultaneous process of non-catalytic transesterification and thermal decomposition as treatedin supercritical methanol. The product treated with 450C in reaction temperature, 40MPa in pressure and4 minutes in time is almost same properties with traditional biodiesel fuel.
Suppressors of Cytokine Signaling (SOCS) Proteins and JAK/STAT Pathways (2011)

Various cytokines are involved in the regulation of the immune system and inflammation. Dysregulation of cytokine signaling can cause a variety of diseases, including allergy, autoimmune diseases, inflammation, and cancer. Most cytokines use the so-called janus kinase/signal transducer and activator of transcription pathway, and this pathway is negatively regulated by suppressors of cytokine signaling (SOCS) proteins. SOCS proteins bind to janus kinase and to certain cytokine receptors and signaling molecules, thereby suppressing further signaling events. Studies have shown that SOCS proteins are key physiological regulators of inflammation. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of adaptive immunity.
Cellular and Molecular Mechanisms of Coronary Artery Spasm (2000)

Coronary artery spasm plays an important role in the pathogenesis of a wide variety of ischemic heart diseases, especially in the Japanese population. Because coronary artery spasm can be induced by a variety of stimuli with different mechanisms of action, the occurrence of the spasm appears to be due to the local hyperreactivity of the coronary artery rather than to an enhanced stimulation with a single mechanism of action. Several lines of evidence indicate that coronary artery spasm is caused primarily by smooth muscle hypercontraction whereas the contribution of endothelial dysfunction may be minimal. In order to elucidate the cellular and molecular mechanisms of the spasm, porcine models of the spasm were developed. In the first model with balloon injury and high-cholesterol feeding, a close topological correlation between the early atherosclerotic lesions and the spastic sites was noted, whereas in the second model with an inflammatory cytokine the potential importance of coronary inflammatory changes, especially at the adventitia, was noted. Subsequent studies in vivo and in vitro demonstrated that protein kinase C (PKC) and Rho-kinase are substantially involved in the intracellular mechanism of the spasm, resulting in increases in the mono- and diphosphorylations of myosin light chain (MLC). Furthermore, molecular biological analyses demonstrated that Rho-kinase is upregulated at the spastic site (at all levels, including mRNA, protein, and activity), resulting in the inhibition of MLC phosphatase through the phosphorylation of its myosin binding subunit and thereby causing the increase in MLC phosphorylations. Preliminary results also suggest that the long-term inhibition of Rho-kinase is effective in inhibiting the development of arteriosclerotic vascular lesions in several porcine models. Thus, Rho-kinase could be regarded as a novel therapeutic target for coronary arteriosclerosis in general and coronary artery spasm in particular.
From mutation mapping to phenotype cloning. (1995)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Guided-mode resonance Brewster filter (1998)

A new type of optical filter is predicted theoretically and verified experimentally. The filter operates under guided-mode resonance conditions in a thin-film waveguide grating. A high-efficiency reflection filter response is produced at the Brewster angle at which TM reflection is classically prohibited. Low-reflectance sidebands are obtained that are adjacent to the resonance peak induced by the Brewster effect in the neighborhood of the resonance peak. A double-layer waveguide grating yields 94% experimental reflectance at the thin-film Brewster angle for a Gaussian laser beam with TM polarization at the 1064-nm wavelength.
Profiling the immune responses in patient sera with peptide and cDNA display libraries. (2000)

Peptide and cDNA phage display libraries can be used to determine the specificities of antibodies present in the whole sera of patients where information about the parental antigens is unknown. In this respect, patient serum antibody binding ligands have been identified. Such ligands would facilitate the design of diagnostic assays and therapeutic vaccines. In the case of cancer, this novel technology is expected to improve our understanding of the immune responses against tumour cells and to discriminate between autoantigen and true tumour specific antigens. Here, we review work on how peptide and cDNA phage display libraries can be used to address the specificity of the immune responses in patients with autoimmune diseases and cancer.
Chymase and angiotensin converting enzyme activities in a hamster model of glaucoma filtering surgery (2002)

These findings show that not only ACE but also chymase contributes to the formation of Ang II in the healing of sclerocorneal wounds in hamster eyes. This leads to the suggestion that ACE inhibitors or chymase inhibitors could potentially inhibit scarring in glaucoma filtering surgery.
Transdominant inhibition of wild-type human immunodeficiency virus type 2 replication by an envelope deletion mutant (1993)

The envelope glycoprotein of human immunodeficiency virus type 2 (HIV-2) is primarily responsible for virus attachment and entry into the target cell population. We constructed an HIV-2 mutant virus containing an in-frame deletion within the putative CD4-binding sequences of the envelope glycoprotein and confirmed that the mutant envelope is unable to bind CD4 and that the mutant virus is noninfectious. To investigate whether this mutant could dominantly interfere with wild-type replication, we coexpressed proviral DNAs of both wild-type and mutant viruses in cells and assayed the production of infectious HIV-2 virions. Interference with virus replication was indeed observed with mutant DNA, and a maximal effect was achieved with 10-fold excess mutant DNA over wild-type DNA in the cotransfection experiments. The transdominant effect on virus replication does not appear to be at the level of wild-type envelope expression or gp120-CD4 interaction. Rather, the interference may be at the level of mixed-oligomer formation during progeny virus assembly and may occur by either destabilizing the multimeric structure of gp120 or forming a defective mixed multimeric gp120 which is unable to complete the receptor binding and/or postbinding events needed for infection.
Antimicrobial Activity of Chitosan Derivatives Containing N-Quaternized Moieties in Its Backbone: A Review (2014)

Chitosan, which is derived from a deacetylation reaction of chitin, has attractive antimicrobial activity. However, chitosan applications as a biocide are only effective in acidic medium due to its low solubility in neutral and basic conditions. Also, the positive charges carried by the protonated amine groups of chitosan (in acidic conditions) that are the driving force for its solubilization are also associated with its antimicrobial activity. Therefore, chemical modifications of chitosan are required to enhance its solubility and broaden the spectrum of its applications, including as biocide. Quaternization on the nitrogen atom of chitosan is the most used route to render water-soluble chitosan-derivatives, especially at physiological pH conditions. Recent reports in the literature demonstrate that such chitosan-derivatives present excellent antimicrobial activity due to permanent positive charge on nitrogen atoms side-bonded to the polymer backbone. This review presents some relevant work regarding the use of quaternized chitosan-derivatives obtained by different synthetic paths in applications as antimicrobial agents.
Synthesis, Structure–Activity Relationships, and in Vivo Efficacy of the Novel Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor 5-Chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) Currently in Phase 1 and Phase 2 Clinical Trials (2013)

The synthesis, preclinical profile, and in vivo efficacy in rat xenograft models of the novel and selective anaplastic lymphoma kinase inhibitor 15b (LDK378) are described. In this initial report, preliminary structure-activity relationships (SARs) are described as well as the rational design strategy employed to overcome the development deficiencies of the first generation ALK inhibitor 4 (TAE684). Compound 15b is currently in phase 1 and phase 2 clinical trials with substantial antitumor activity being observed in ALK-positive cancer patients.
Octave-spanning frequency comb generation in a silicon nitride chip (2011)

We demonstrate a frequency comb spanning an octave via the parametric process of cascaded four-wave mixing in a monolithic, high-Q silicon nitride microring resonator. The comb is generated from a single-frequency pump laser at 1562 nm and spans 128 THz with a spacing of 226 GHz, which can be tuned slightly with the pump power. In addition, we investigate the RF amplitude noise characteristics of the parametric comb and find that the comb can operate in a low-noise state with a 30 dB reduction in noise as the pump frequency is tuned into the cavity resonance.
A Microfluidic Device for Kinetic Optimization of Protein Crystallization and In Situ Structure Determination (2006)

The unprecedented economies of scale and unique mass transport properties of microfluidic devices made them viable nano-volume protein crystallization screening platforms. However, realizing the full potential of microfluidic crystallization requires complementary technologies for crystal optimization and harvesting. In this paper, we report a microfluidic device which provides a link between chip-based nanoliter volume crystallization screening and structure analysis through "kinetic optimization" of crystallization reactions and in situ structure determination. Kinetic optimization through systematic variation of reactor geometry and actuation of micromechanical valves is used to screen a large ensemble of kinetic trajectories that are not practical with conventional techniques. Using this device, we demonstrate control over crystal quality, reliable scale-up from nanoliter volume reactions, facile harvesting and cryoprotectant screening, and protein structure determination at atomic resolution from data collected in-chip.
Temperature-Dependent Adsorption of Pluronic F127 Block Copolymers onto Carbon Black Particles Dispersed in Aqueous Media (2002)

The adsorption properties of Pluronic F127 poly(ethylene oxide)−poly(propylene oxide)−poly(ethylene oxide) PEO−PPO−PEO block copolymer onto carbon black (CB) particles dispersed in water have been investigated. The CB particles have fractal structure according to small-angle neutron scattering (SANS) measurements. The Langmuir isotherm could describe the adsorption behavior of Pluronic F127 onto CB particles below the block copolymer critical micellization concentration (CMC). Temperature plays an important role in determining the thickness and structure of the adsorbed layer. Below the temperature where micelles start forming (CMT), the added Pluronic F127 block copolymer molecules contribute to an increase of the adsorbed layer thickness (determined by dynamic light scattering) by forming a monolayer. Above the CMT, SANS experiments, performed under contrast matching conditions where either the block copolymer or the CB particles were rendered “invisible”, confirmed that the adsorbed layer had structure and dimensions similar to these of Pluronic F127 block copolymer micelles that form in aqueous solution in the absence of CB. One of the aims of this work is to provide information on how to control the adsorbed layer thickness and structure (and correspondingly, colloidal stability) by tuning variables such as temperature, block copolymer concentration, and/or solvent quality.
Combination immunotherapy with anti-CD20 and anti-HLA-DR monoclonal antibodies induces synergistic anti-lymphoma effects in human lymphoma cell lines (2007)

Rituximab is effective in about one half of patients with indolent lymphoma. Even these patients relapse and develop rituximab resistance. To increase potency and circumvent resistance, the anti-lymphoma effects of rituximab, an anti-CD20 MAb(1), combined with chLym-1(2), an anti-HLA-DR MAb, were assessed in human lymphoma cell lines by examining growth inhibition and cell death, apoptosis induction, ADCC(3) and CDC(4). There were additive effects in all assays and synergism in cell lines, such as B35M, which displayed resistance to either MAb alone. In B35M cells, combined rituximab and chLym-1 induced a 27-fold direct reduction in viable cells, whereas equivalent concentrations of rituximab or chLym-1 alone induced only a 1-fold and 10-fold reduction in viable cells, respectively. Because these results occurred at MAb concentrations readily achievable in patients, they suggest that this combination immunotherapy regimen may increase the potency and range of effectiveness of these MAbs in lymphoma patients.
Designed Ankyrin Repeat Proteins as Anti‐Idiotypic‐Binding Molecules (2007)

According to the network theory antibodies may act as antigens thus generating anti-idiotypic antibodies that can function as regulators of immune responses. Designed ankyrin repeat proteins (DARPins) are a new class of binding proteins and may serve as an alternative to antibodies. Selections from large DARPin libraries against the variable regions of a murine monoclonal anti-human IgE antibody, termed BSW17, yielded two highly specific anti-idiotypic DARPins both with high affinity. Their binding characteristics were comparable with these of a previously selected anti-idiotypic antibody. In vitro cell assays showed that the anti-idiotypic DARPins were able to inhibit the binding of BSW17 to cell-bound IgE and prevented BSW17 functional activity. These experiments demonstrate the possibility to isolate anti-idiotypic DARPins recognizing idiotypic determinants analogous to antibodies. In the future these DARPins may be further analyzed for their potential as putative vaccine candidates.
A novel electrochemically synthesized biodegradable thin film of polypyrrole–polyethyleneglycol–polylactic acid nanoparticles (2006)

Nanoparticles having reactive pyrrole residues were prepared from poly(1-ethoxyethylglycidyl ether)-block-poly(L,L-lactide) block copolymer. The nanoparticles were electropolymerized in aqueous media through the oxidation of the pyrrole residue and in the presence of pyrrole to form a nanocomposite thin film. The novel synthesis of these pyrrole-functionalized nanoparticles is described and the electrochemical deposition of the corresponding coating is characterized using electrochemistry, SEM and EDX.
Syntheses of FDA Approved HIV Protease Inhibitors (2001)

The treatment of HIV and AIDS was revolutionized by the introduction of peptidomimetic aspartyl protease inhibitors. One of the major limitations of this type of therapy is that higher therapeutic doses are necessary because of the presence of 'peptide-like' features in the drugs. Therefore, adequate supplies and cost effective syntheses of these drugs are of utmost importance. To date, there are six protease inhibitors approved by the United States Food and Drug Administration (FDA) for the treatment of HIV and AIDS. This review focuses on the published syntheses of currently FDA approved HIV protease inhibitor drugs, their isosteres and ligands.