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We sought to determine the predictors of primary episodes of mild diastolic dysfunction (DD) in a cohort of women aged >45 years, who had >2 echocardiography from 2009 to 2012. Patients were excluded if they had prior diagnosis of coronary artery disease, heart failure, valvular heart disease or echocardiographic evidence of DD. Mild DD was defined as: left ventricular ejection fraction>50%, E/A ratio<0.75, and E/e’?8. Out of the total 758 subjects (age 64.15±7.24 years), 109 (14.3%) had developed mild DD, during a mean followup period of 3 years. Independent predictors of mild DD included: age (P<0.001), history of hypertension (P=0.022), body mass index (BMI) (P<0.001), total triglycerides (TG) (P=0.016), inter ventricular septal thickness (P=0.015) and brachial-ankle pulse wave velocity (baPWV) ?16?m?s-1(P<0.001). E/A ratio was inversely associated with age (r=-0.337, P<0.001), baPWV (r=-0.359, P<0.001), BMI (r=-0.290, P<0.001) and TG (r=-0.255, P<0.001). The Area Under roc Curve for a linear combination of age, BMI, baPWV and TG was 0.738 (95% confidence interval: 0.683–0.804, P<0.001), which was superior to any of the variables taken alone. In summary, many middle-aged or elderly women may develop mild DD within a relatively short period of 3 years. Several subclinical abnormalities and cardiovascular parameters were determined to contribute to the onset of DD.

Biomechanical studies were designed to determine the dynamic progression of the uterine cervix of pregnant rats at various stages of gestation and to determine its functions in retaining the fetus while at the same time undergoing characteristic softening to allow for dilatation at parturition. Whole cervices from Sprague-Dawley rats at 10, 15, and 21 days gestation and at 3 days postpartum were subjected to detailed biomechanical studies. Tension–length change, tension–diameter, pressure–area, stress–diameter, and stress–strain curves were calculated using analytical methods adopted from vascular mechanics. The circular diameter of the tissue was greatly increased as pregnancy advanced. Cervix volume increased, while tissue wall stress and cervix pressure were both maintained in a constant range throughout pregnancy. The compliance increased until term. The rat cervix undergoes two mechanical changes, a change in mechanical properties and a increase in volume, that allow it to maintain its two physiological functions of: (a) softening in preparation for delivery, and (b) at the same time remaining undilated in order to maintain fetuses in utero.

The extracellular signal regulated kinase (ERK1 and ERK2) signal transduction pathways play a critical role in cell proliferation. Hyperactivation of the ERK proteins either through increased expression of membrane-bound growth factor receptors or genetic mutations of upstream proteins is thought to be involved in the pathogenesis of many human cancers. Thus, targeted inhibition of ERK signaling is viewed as a potential approach to prevent cancer cell proliferation. Currently, no specific inhibitors of the ERK proteins exist. Moreover, most kinase inhibitors lack specificity because they target the ATP binding region, which is well conserved among the protein kinase families. Taking advantage of recently identified ERK docking domains, which are reported to facilitate substrate protein interactions, we have used computer-aided drug design (CADD) to identify novel small molecular weight ERK inhibitors. Following a CADD screen of over 800 000 molecules, 80 potential compounds were selected and tested for activity in biological assays. Several compounds inhibited ERK-specific phosphorylation of ribosomal S6 kinase-1 (Rsk-1) or the ternary complex factor Elk-1 (TCF/Elk-1), both of which are involved in promoting cell proliferation. Active compounds showed a dose-dependent reduction in the proliferation of several cancer cell lines as measured by colony survival assays. Direct binding between the active compounds and ERK2 was indicated by fluorescence quenching. These active compounds may serve as lead candidates for development of novel specific inhibitors of ERK−substrate interactions involved in cell proliferation.

Stoichiometric reactions can be used to remove H2 and the associated kinetic and thermodynamic barriers that lead to low dehydrocyclodimerization selectivity during alkane reactions on cation-modified H-ZSM5. O2 co-reactants can form H2O in exothermic reactions that balance the enthalpy of endothermic dehydrogenation steps. O2 reacts preferentially with H2 via homogeneous and heterogeneous pathways, but also with hydrocarbons as H2 is depleted; thus, it must be gradually introduced as H2 forms in dehydrogenation reactions. Staged O2 protocols significantly increased aromatics yields during C3H8 reactions on unexchanged and on Ga- and Zn-exchanged H-ZSM5. On Ga/H-ZSM5, the maximum aromatic yields increased from 54% to 68% and aromatization/cracking selectivity ratios increased from 2.1 to 3.9 when O2 was introduced gradually into a gradientless batch reactor as H2 formed. O2 introduced was converted to H2O with >95% selectivity; an equivalent amount of O2 initially added with C3H8 led to low H2O selectivities (&lt;60%). Similar effects of O2 addition and of staging protocols were observed for alkane reactions on H-ZSM5 and Zn/H-ZSM5. Staging strategies led to selective use of O2 to remove thermodynamic and kinetic bottlenecks and to unprecedented aromatics yields during alkane reactions on cation-exchanged H-ZSM5.

Hydrogen removal steps limit alkane dehydrogenation reactions on cation-exchanged H−ZSM5 and cause desorption bottlenecks and the formation of hydrogen-rich reaction intermediates and products. For this reaction, the catalytic surface acts for all kinetic purposes as if it were in equilibrium with a H2 pressure greater than in the prevalent gas phase. The hydrogen chemical potential within adsorbed intermediates is described rigorously by a virtual H2 pressure, defined as that required to achieve the prevalent surface hydrogen content if adsorption−desorption steps were equilibrated. These virtual pressures can be measured from the deuterium content in products formed from C3H8/D2 reactants. H2 virtual pressures are high during propane reactions on H−ZSM5, because recombinative desorption of hydrogen atoms formed in C−H activation steps is slow. H2 virtual pressures decrease as Zn cations replace protons in H−ZSM5, because cations catalyze hydrogen adsorption−desorption steps and provide a kinetic path for communication between H2 in the gas phase and propane-derived reaction intermediates. As a result, the addition of H2 to C3H8 reactants decreases propane reaction rates and aromatics selectivity on Zn/H−ZSM5, causing it to resemble kinetically H−ZSM5. The hydrogen chemical potential on these catalytic surfaces and the hydrogen content within reactive intermediates reflect the rate at which hydrogen is formed in either C−H bond activation steps or in the dissociative chemisorption of gas-phase H2. The reaction pathways for species derived from each of these two H-sources are kinetically indistinguishable. Both sources contribute hydrogen atoms or hydrogen-rich species to the prevalent pool of reactive intermediates, the hydrogen content of which determines the rate and selectivity of all surface chemical reactions.

Co/H-ZSM5 catalyzes propane dehydrogenation and aromatization reactions. Initial product selectivities, product site-yields, and the ¹³C content and distribution in the products of 2-¹³C-propane show that propane undergoes two primary reactions&sbd;dehydrogenation to propene and H2 and cracking to methane and ethene. Propene and ethene then form aromatics via oligomerization−cracking reactions and both ethene and propene hydrogenate to form ethane and propane, respectively, via both hydrogen transfer from coadsorbed intermediates and dissociative adsorption of H2. These reaction pathways resemble those occurring on H-ZSM5, but Co cations provide an alternate pathway for the removal of hydrogen atoms in adsorbed intermediates as H2. A kinetic model was used to describe experimental rates based on these observations and to obtain rate constants for individual reaction steps as a function of Co content and H2 concentration. H2 inhibits propane dehydrogenation to propene and alkene conversion to aromatics, and increases the rate and the rate constant for ethene hydrogenation. Rate constants were obtained for propane reactions on H-ZSM5 and Co/H-ZSM5 (Co/Al = 0.05−0.22). Propane dehydrogenation (k1), ethene hydrogenation (k3), and alkene dehydrocyclization (k4) rate constants increased with increasing Co/Al ratio, because Co cations catalyze both the recombinative desorption of H2 and its microscopic reverse, the dissociative adsorption of H2. Co cations increase the reversibility of hydrogen adsorption−desorption steps, and in this manner, they increase the deuterium content in all products of C3H8-D2 reactions. Propane cracking rate constants (k2) were not influenced by Co cations, because cracking occurs on acid sites and its stoichiometry and mechanism do not require hydrogen.

Co/H-ZSM5 catalysts with Co/Al ratios of 0.09−0.22 were prepared by aqueous exchange. Turnover rates for propane conversion to propene and to C6−C8 aromatics on these catalysts are about 10-fold higher than on H-ZSM5. The selectivities to propene, aromatics, and H2 are also higher on Co/H-ZSM5 than on H-ZSM5. The rate of D2 exchange with OH groups increases with increasing Co/Al ratio, suggesting that Co cations catalyze D2 dissociative chemisorption steps that limit the rate of isotopic exchange. Co cations also catalyze hydrogen recombinative desorption steps, which limit the rate of propane dehydrogenation and aromatization reactions. The density of residual zeolitic hydroxyls was measured by D2−OH isotopic exchange and by changes in the intensity of OH infrared bands as a function of Co content. D2−OH and infrared measurements showed that Co²⁺ cations replace 1.1−1.3 zeolitic protons, suggesting the predominant presence of Co²⁺−O−Co²⁺ dimers, with some Co²⁺ monomers, each bridging two next-nearest neighbor Al sites. The location and structure of exchanged Co cations were probed using X-ray absorption spectroscopy (XAS) and temperature-programmed reduction (TPR). No H2 consumption was detected up to 1273 K during TPR in any of the Co/H-ZSM5 samples, consistent with the absence of CoOx crystallites, which reduce at ~800 K. In situ near-edge X-ray absorption studies confirmed that Co species remain as divalent cations during exposure to H2 or C3H8 at 773 K. Near-edge and fine structure analysis detected Co²⁺ cations with similar structure in all Co/H-ZSM5 samples (Co/Al &lt; 0.22), and Co coordination changes from octahedral to tetrahedral upon sample dehydration at 773 K in He. Radial structure functions showed weak contributions from the first and second shells around Co. This reflects the nonuniform nature of the distance and orientation in Al−Al next-nearest neighbor sites in ZSM5.

Light microscopy studies on the fish cracker gel and expanded product (‘keropok’) emphasised the role of fish proteins in the starch expansion process. The addition of salt (20 g kg⁻¹) in the ‘keropok’ helped to distribute evenly the starch in the fish protein. Formation of thin fish muscle bundles assisted the expansion of ‘keropok’. At 700–900 g kg⁻¹ fish content, the fish muscle bundles formed a continuous network that caused a drop in the ‘keropok’ expansion. From the scanning electron microscopy study, ridges were found in samples (containing 600–900 g kg⁻¹ fish content) with 20 g kg⁻¹ salt at high magnification. © 1999 Society of Chemical Industry

The effect of steaming time on ‘keropok’ was studied. The morphology of the starch granules in keropok gel at different steaming times was examined using scanning electron microscopy (SEM). There was an optimum time for the steaming of keropok which gave the best linear expansion and hardest texture of steamed gel. This occurred when the starch granules were expanded to their largest sizes and before fragmentation of the granules. A steaming time of 20–30 min is sufficient to cook the keropok gel. Excessive steaming time will result in a poor-quality product as well as extra production costs. © 1999 Society of Chemical Industry

Industrial companies are facing more pressure to improve the recyclability performance of their new designed products. The concept of Environmental Conscious Design (ECD) has been adopted to assist more concerning about the environmental impact of the products at the early stage of designing. This new trend requires that the design strategy should be modified to integrate environmental constraints. This paper develops an Environmental Design Support Tool (EDST) to help designers improve their product in aspect of the environment. The proposed EDST is capable of evaluating the new designed product in terms of environmental sustainability, i.e., material selection, recyclability evaluation, and disassemblability analyses.

Two variations of a new method of TEM metal sample preparation are proposed, hereby labeled RUM1 and RUM2, for ”reverse ultra-microtomy” 1 and 2, respectively. With these techniques, the TEM samples are formed from bulk specimens by successively slicing off layers, with an ultra-microtome, until the remnant is partially thinned to electron transparency. This requires the sample to be embedded with excellent adhesion in a mounting material whose mechanical properties resemble that of the sample. While these methods are by far slower than ordinary microtomy wherein the individual slices are used as samples, preparation times are comparable to those for creating TEM samples by standard techniques. Furthermore, the methods (i) can be used where electropolishing fails, (ii) can be favorably applied to finely layered materials and composites, (iii) permit studies of near-surface structure gradients, and (iv) permit the simultaneous observation of an original surface and the underlying material. The methods have been successfully demonstrated through comparisons between samples created through RUM1 and 2 and standard TEM samples. Artifacts caused by the new method of reverse microtoming are shown to be very much reduced compared to direct microtoming.

The formation of growth increments in the otoliths of wild-captured larvae of milkfish Chanos chanoswas validated by the oxytetracycline-labeling method. Immersion of the fish in 400–500 mg oxytetracycline/L for 24 h is recommended for marking the otoliths of milkfish larvae. A golden-yellow band and the newly deposited growth increments in the otolith were both discernible after marking. Otolith growth increments were deposited at the rate of about one per day, and their formation rate was unaffected by the growth rate of the fish. However, increment width varied with the growth rate of fish. Therefore, otolith growth increments are a valid characteristic for determining daily age and for studying the growth history of wild milkfish larvae.

Tube spinnability is defined as the maximum thickness reduction before either fracture or buckling under the given roller geometry, feed rate, and the speed of the mandrel during the tube spinning of a metal. There are two ways employed to experimentally determine the tube spinnability of the full-annealed and solution-treated AA 2024 and 7075 aluminum alloys. One is to reduce the thickness stepwise to the final thickness without failure the tube. The other is the one-path spinning with continuous reduction in wall thickness of preform from initial to the final thickness without buckling to determine the achieved maximum reduction. Using continuous reduction test, the determined macro-spinnability of full-annealed AA 2024 aluminum alloys is 75% and 7075 aluminum is 74%. Whereas, when examined by scanning electron microscope, the deformation tongue is visible on the outer surface as the thickness reduction higher above 50% for both full annealed 2024 and 7075 aluminum alloys. However, for both solution-treated 2024 and 7075 tubes, the spinnability is lower than that of full-annealed conditions. The discrepancy between the reduction test and microscopic spinnability will be discussed in terms of the microstructure and the mechanical properties.

An inverse correlation between geographic distribution of liver cancer incidence and the selenium (Se) contents of whole blood and grains was observed in Qidong county, Jiangsu province, a high liver cancer area of the People’s Republic of China. Animal experiments demonstrated that supplementation of Se reduced the incidence of liver cancer in rats exposed to aflatoxin B1. Se was also shown to inhibit the growth of transplanted tumors. A lower incidence of liver preneoplastic alterations and reduction of hepatitis B virus infection in ducks by Se-supplementation was observed, and three pilot studies for a Se-intervention trial on human liver cancer were carried out on the residents of Qidong county. A protective effect on the cellular DNA damage induced by aflatoxin B1was observed in lympocytes from human with Se-supplements.

The Notch signalling pathway is involved in many processes where cell fate is decided. Previous work showed that Notch is required at successive steps during R8 specification in the Drosophila eye. Initially, Notch enhances atonal expression and promotes atonal function. After atonal autoregulation has been established, Notch signalling represses atonal expression during lateral specification. In this paper we investigate which known components of the Notch pathway are involved in each signalling process. Using clonal analysis we show that a ligand of Notch, Delta, is required along with Notch for both proneural enhancement and lateral specification, while the downstream components Suppressor-of-Hairless and Enhancer-of-Split are involved only in lateral specification. Our data point to a distinct signal transduction pathway during proneural enhancement by Notch. Using misexpression experiments we also show that particular Enhancer-of-split bHLH genes can differ greatly in their contribution to lateral specification.

Tube spinnability is defined as the maximum thickness reduction before either fracture or buckling under the given roller geometry, feed rate, and the speed of the mandrel during the tube spinning of a metal. There are two ways employed to experimentally determine the tube spinnability of the full-annealed and solution-treated AA 2024 and 7075 aluminum alloys. One is to reduce the thickness stepwise to the final thickness without failure the tube. The other is the one-path spinning with continuous reduction in wall thickness of preform from initial to the final thickness without buckling to determine the achieved maximum reduction. Using continuous reduction test, the determined macro-spinnability of full-annealed AA 2024 aluminum alloys is 75% and 7075 aluminum is 74%. Whereas, when examined by scanning electron microscope, the deformation tongue is visible on the outer surface as the thickness reduction higher above 50% for both full annealed 2024 and 7075 aluminum alloys. However, for both solution-treated 2024 and 7075 tubes, the spinnability is lower than that of full-annealed conditions. The discrepancy between the reduction test and microscopic spinnability will be discussed in terms of the microstructure and the mechanical properties.

Wear tests on SiC whisker- and SiC particulate-reinforced 6061-T6 aluminum matrix composites (SiCw/Al and SiCp/Al), fabricated using a high pressure infiltration method, were performed in laboratory air, ion-exchanged water and a 3 pct NaCl aqueous solution using a block-on-ring type apparatus. The effects of environment, applied load, and rotational (sliding) speed on the wear prop-erties against a sintered alumina block were evaluated. Electrochemical measurements in ion-ex-changed water and a 3 pct NaCl aqueous solution were also made under the same conditions as the wear tests. A comparison was made with the properties of the matrix aluminum alloy 6061-T6. The SiC-reinforced composites exhibited better wear resistance compared with the monolithic 6061 Al alloy even in a 3 pct NaCl aqueous solution. Increase in the wear resistance depended on the shape, size, and volume fraction of the SiC reinforcement. Good correlation was obtained between corrosion resistance and corrosion wear. The ratios of wear volume due to the corrosive effect to noncorrosive wear were 23 to 83 pct, depending on the wear conditions.

R8 photoreceptor cells play a primary role in the differentiation of Drosophila eyes. In scabrous (sca) mutants, the pattern of R8 photoreceptor differentiation is altered. The sca gene is predicted to encode a secreted protein related in part to fibrinogen and tenascins. Using expression in Drosophila Schneider cells, we showed that sca encoded a dimeric glycoprotein which was secreted and found in soluble form in the tissue culture medium. The sca protein contained both N- and O-linked carbohydrates and interacted with heparin. This Schneider cell protein was similar to protein detected in embryos. We showed that sca mutations, along with conditional alleles of Notch (N) and Delta (Dl), each affected the pattern of cells expressing atonal (ato), the proneural gene required for R8 differentiation. In normal development, about 1 cell in 20 differentiates into an R8 cell; in the others, ato is repressed. N and Dl were required to repress ato in the vicinity of R8 cells, whereas sca had effects over several cell diameters. Certain antibodies detected uptake of sca protein several cells away from its source. The overall growth factor-like structure of sca protein, its solubility, and its range of effects in vivo are consistent with a diffusible role that complements mechanisms involving direct cell contact. We propose that as the morphogenic furrow advances, cell secreting sca protein control the pattern of the next ommatidial column.

A new V-groove integrated injection logic (v.i.i.l.) is proposed which combines the V-groove technology and the double-diffused bipolar technology. The fabrication processes arc qualitatively described. The lateral p–n–p transistor of the i.i.l. is located on the vertical V-shape surface, and the effective base width is controlled by the combination of the vertical diffusion process and the V-groove etching rate. A 1-dimensional analysis is used and an approximate expression for the collector current of the lateral p–n–p transistor is given. The v.i.i.l. is expected to have a higher production yield than that of the ordinary i.i.l.

A new V-groove double-diffused m.o.s. (v.d.m.o s.) is proposed which combines the V-groove technology and the double-diffused m.o.s. (d.m.o.s.) technology. The fabrication processes arc qualitatively described. The gate is located on the vertical V-shaped surface, and the effective channel length is controlled by the vertical-diffusion process of the double-diffusion step. The v.d.m.o.s. is expected to have a faster speed and higher production yield than the ordinary d.m.o.s.

Tetrahydrofuran (I) undergoes ring cleavage with phenyl dichlorophosphate (II) in the presence of sodium iodide, leading to the formation of 1,4‐diiodobutane (III).

The most conspicuous structural element in the connective tissue of the clam mantle and gill is the amoeboid cell characterized by its large globular oval body and small nucleus, also long cytoplasmic extension and vesicular contents. The Golgi apparatus is very prominent in the amoeboid cell and is characterized by a large number of vesicles associated with its cristernae. Glycogen, .01μ in diameter, and collagen 200 Å in diameter with a 400 Å periodicity, are found within the vacuoles of the amoeboid cells. Extracellular fibrils having a 100 Å diameter and a 200 Å periodicity, are also observed in the connective tissue. From the autoradiographic studies after administration of proline-C14, the fibrils are incorporating proline, which is similar to those of collagen fiber of vertebrates. Organic crystals displaying a concentric pattern which become the calcium spherulites of the shell appear to arise primarily from mineralization of the intercellular collagen-like fibrils. The evidence indicated the calcium crystals in mantle were already organized by the fibers in tissue prior to secretion from the tissue.