Inhibition of angiotensin-converting enzyme increases the nitric oxide levels in canine ischemic myocardium

Since angiotensin-converting enzyme (ACE) produces angiotensin II in the heart, ACE inhibitors may prevent coronary vasoconstriction and increase coronary blood flow. On the other hand, since ACE inhibitors also inhibit kininase II which results in reduced degradation of bradykinin, ACE inhibitors may increase cardiac nitric oxide (NO) levels via stimulation of bradykinin receptors. This study was undertaken to test whether ACE inhibitors increase the cardiac NO levels and coronary blood flow in the ischemic myocardium. In 34 open-chest dogs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery. When either imidaprilat or cilazaprilat of 3 microg/kg/min was infused into the bypass tube for 10 min after reduction of coronary blood flow due to partial occlusion of the bypass tube, coronary blood flow increased from 31 +/- 1 to either 45 +/- 5 or 43 +/- 4 ml/100 g/min despite no changes in coronary perfusion pressure (43 +/- 2 mmHg). During an infusion of either imidaprilat or cilazaprilat, bradykinin and the end-products of NO (nitrate + nitrite) concentrations of coronary venous blood were markedly increased, which were attenuated by either HOE-140 (an inhibitor of bradykinin receptors) or by N(omega)-nitro-L-arginine methyl ester (an inhibitor of NO synthase). We also observed increases in cardiac bradykinin and NO levels due to either imidaprilat or cilazaprilat in the low constant coronary blood flow condition. It is concluded that ACE inhibitors can increase cardiac NO levels via the accumulation of bradykinin in the ischemic myocardium.     

Hyperperfusion syndrome following carotid endarterectomy: evaluation using diffusion-weighted magnetic resonance imaging--case report

OBJECTIVE: Epidemiological evidence suggests that resistance to insulin is the common nexus of the accumulation of factors in patients at high cardiovascular risk. To find a test which enables resistance to insulin to be identified in large populations will allow preventive and therapeutic measures to be taken. DESIGN: Crossover. SETTING: Carrascosa del Campo and Cuenca Health Centres. PARTICIPANTS: 408 patients (154 men and 254 women), all the non-diabetic obese patients at the two health centres, were studied. MEASUREMENTS AND MAIN RESULTS: Levels of cholesterol, triglycerides and uric acid were measured. Patients were medically examined, and blood pressure, waist and hip measurements, toxic habits and cardiovascular history were found. They were classified by pathology and normograms. The O'Sullivan and microalbuminuria tests were performed, and all the statistical associations with biochemical and medical characteristics were studied. The O'Sullivan test was significantly associated (p < 0.01) with cardiovascular risk and insulin-resistance factors such as hypercholesterolaemia (RR 1.63), hypertension (RR 1.92), hypertriglyceridaemia (RR 2.47), hyperuricaemia (RR 1.80), with the Berglund resistance index (RR 1.52) and the microalbuminuria test (RR 1.83). The association was more consistent when there were a number of factors combining. There was no relationship with the waist/hip index found. CONCLUSION: The O'Sullivan test, on its own or with the microalbuminuria test, seems very useful for identifying obese subjects with resistance to insulin.     

Highly reliable a‐IGZO TFTs on a plastic substrate for flexible AMOLED displays

We have successfully reduced threshold voltage shifts of amorphous In–Ga–Zn–O thin‐film transistors (a‐IGZO TFTs) on transparent polyimide films against bias‐temperature stress below 100 mV, which is equivalent to those on glass substrates. This high reliability was achieved by dense IGZO thin films and annealing temperature below 300 °C. We have reduced bulk defects of IGZO thin films and interface defects between gate insulator and IGZO thin film by optimizing deposition conditions of IGZO thin films and annealing conditions. Furthermore, a 3.0‐in. flexible active‐matrix organic light‐emitting diode was demonstrated with the highly reliable a‐IGZO TFT backplane on polyimide film. The polyimide film coating process is compatible with mass‐production lines. We believe that flexible organic light‐emitting diode displays can be mass produced using a‐IGZO TFT backplane on polyimide films.     

Aerodynamic structure of a flat plate laminar boundary layer with diffusion flame

An aerodynamic structure of a laminar boundary layer over a flat plate with uniform fuel injection from the flat plate and with diffusion flame is investigated numerically. Elliptic type conservation equations are used to take into account the pressure variation within the boundary layer. Velocities and the pressure are solved numerically by SIMPLER algorithm. One step irreversible chemical reaction of methane is assumed. An Arrhenius type chemical reaction rate model is assumed and the pre-exponential factor is varied from 1.0 × 10¹² to 1.0 × 10³⁰ m³/(kg s) as a parameter of the reactivity in order to elucidate the effect of the reactivity on the structure of the boundary layer. When the chemical reaction is very fast, the leading edge of the reaction zone reaches the flat plate. As the chemical reaction rate is decreased with a decrease in the pre- exponential factor, the leading edge of the reaction zone parts from the flat plate and it shifts downstream. The fuel is injected in front of the leading edge of the reaction zone, where the air is dominant, and the oxygen penetrates into the fuel dominant zone through the region between the leading edge and the flat plate. As a consequence, a premixed gas is formed around the leading edge of the reaction zone. The premixed gas seems to react in the region apart from the main visible flame.Part of this work was presented at ICCM 86, Tokyo, Japan, May 25–29, 1986     

Making exhaustive search programs deterministic

This paper presents a technique for compiling a Horn-clause program intended for exhaustive search into a GHC (Guarded Horn Clauses) program. The technique can be viewed also as a transformation technique for Prolog programs which compiles away the ‘bagof’ primitive and non-determinate bindings. The class of programs to which our technique is applicable is shown with a static checking algorithm; it is nontrivial and could be extended. An experiment on a compiler-based Prolog system showed that our technique improved the efficiency of exhaustive search by 6 times for a permutation generator program. This compilation technique is important also in that it exploits the AND-parallelism of GHC for parallel search.     

An Engineered Biliverdin-Compatible Cyanobacteriochrome Enables a Unique Ultrafast Reversible Photoswitching Pathway

Cyanobacteriochromes (CBCRs) are promising optogenetic tools for their diverse absorption properties with a single compact cofactor-binding domain. We previously uncovered the ultrafast reversible photoswitching dynamics of a red/green photoreceptor AnPixJg2, which binds phycocyanobilin (PCB) that is unavailable in mammalian cells. Biliverdin (BV) is a mammalian cofactor with a similar structure to PCB but exhibits redder absorption. To improve the AnPixJg2 feasibility in mammalian applications, AnPixJg2_BV4 with only four mutations has been engineered to incorporate BV. Herein, we implemented femtosecond transient absorption (fs-TA) and ground state femtosecond stimulated Raman spectroscopy (GS-FSRS) to uncover transient electronic dynamics on molecular time scales and key structural motions responsible for the photoconversion of AnPixJg2_BV4 with PCB (Bpcb) and BV (Bbv) cofactors in comparison with the parent AnPixJg2 (Apcb). Bpcb adopts the same photoconversion scheme as Apcb, while BV4 mutations create a less bulky environment around the cofactor D ring that promotes a faster twist. The engineered Bbv employs a reversible clockwise/counterclockwise photoswitching that requires a two-step twist on ~5 and 35 picosecond (ps) time scales. The primary forward P_fr → P_o transition displays equal amplitude weights between the two processes before reaching a conical intersection. In contrast, the primary reverse P_o → P_fr transition shows a 2:1 weight ratio of the ~35 ps over 5 ps component, implying notable changes to the D-ring-twisting pathway. Moreover, we performed pre-resonance GS-FSRS and quantum calculations to identify the Bbv vibrational marker bands at ~659,797, and 1225 cm⁻¹. These modes reveal a stronger H-bonding network around the BV cofactor A ring with BV4 mutations, corroborating the D-ring-dominant reversible photoswitching pathway in the excited state. Implementation of BV4 mutations in other PCB-binding GAF domains like AnPixJg4, AM1_1870g3, and NpF2164g5 could promote similar efficient reversible photoswitching for more directional bioimaging and optogenetic applications, and inspire other bioengineering advances.     

Chemical Modification of Phage-Displayed Helix-Loop-Helix Peptides to Construct Kinase-Focused Libraries

Conformationally constrained peptides hold promise as molecular tools in chemical biology and as a new modality in drug discovery. The construction and screening of a target-focused library could be a promising approach for the generation of de novo ligands or inhibitors against target proteins. Here, we have prepared a protein kinase-focused library by chemically modifying helix-loop-helix (HLH) peptides displayed on phage and subsequently tethered to adenosine. The library was screened against aurora kinase A (AurA). The selected HLH peptide Bip - 3 retained the α-helical structure and bound to AurA with a K_D value of 13.7 μM. Bip - 3 and the adenosine-tethered peptide Bip - 3 - Adc provided IC₅₀ values of 103 μM and 7.7 μM, respectively, suggesting that Bip - 3 - Adc bivalently inhibited AurA. In addition, the selectivity of Bip - 3 - Adc to several protein kinases was tested, and was highest against AurA. These results demonstrate that chemical modification can enable the construction of a kinase-focused library of phage-displayed HLH peptides.     

New polylactide/layered silicate nanocomposites. 5. Designing of materials with desired properties

Understanding the structure/property relationship in polymer/layered silicate nanocomposites is of great importance in designing materials with desired properties. In order to understand these relations, a series of polylactide (PLA)/organically modified layered silicate (OMLS) nanocomposites have been prepared using a simple melt extrusion technique. Four different types of OMLS have been used for the preparation of nanocomposites, three were modified with functionalized ammonium salts while fourth one was a phosphonium salt modified OMLS. The structure of the nanocomposites in the nanometer scale was characterized by using wide-angle X-ray diffraction and transmission electron microscopic observations. Using four different types of layered silicates modified with four different types of surfactants, the effect of OMLS in nanocomposites was investigated by focusing on four major aspects: structural analysis, thermal properties and spherulite morphology, materials properties, and biodegradability. Finally, we draw conclusions about the structure/property relationship in the case of PLA/OMLS nanocomposites.     

Synthesis of ordered polymers by direct polycondensation

A series of ordered polymers can be prepared by direct polycondensation of nonsymmetric monomers using diphenyl(2,3-dihydro-2-oxo-3-benzothiazolyl)phosphonate (1) as a condensing agent. The methodology and requirements for the preparation of ordered polymer are first presented. Then, the following ordered polymer syntheses are described: (1) ordered polyamides (head-to-head or tail-to-tail) from a symmetric monomer and a nonsymmetric monomer. (2) the ordered polyamide (head-to-tail) from a symmetric monomer and a nonsymmetric monomer. (3) the ordered (-abcd-) polymer from a pair of two symmetric monomers and a nonsymmetric monomer. (4) the ordered (-abcdef-) polymer from nonsymmetric monomers, XabX, YcdY, and ZefZ.