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Muscle atrophy and cachexia are common comorbidities among patients suffering from cancer, chronic obstructive pulmonary disease, and several other chronic diseases. The peptide hormone ghrelin exerts pleiotropic effects including the stimulation of growth hormone secretion and subsequent increase of insulin-like growth factor-1 levels, an important mediator of muscle growth and repair. Ghrelin also acts on inflammation, appetite, and adipogenesis and therefore has been considered a promising therapeutic target for catabolic conditions. We previously reported on the synthesis and properties of an indane based series of ghrelin receptor full agonists which led to a sustained increase of insulin-like growth factor-1 in a dog pharmacodynamic study. Herein we report on the identification of a series of pyrrolidine or piperidine based full agonists and attempted optimization to give compounds with profiles suitable for progression as clinical candidates.

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In this work, the topic of the detrimental contact effects in organic thin-film transistors (OTFTs) is revisited. In this case, contact effects are considered as a tool to enhance the characterization procedures of OTFTs, achieving more accurate values for the fundamental parameters of the transistor threshold voltage, carrier mobility and on-off current ratio. The contact region is also seen as a fundamental part of the device which is sensitive to physical, chemical and fabrication variables. A compact model for OTFTs, which includes the effects of the contacts, and a recent proposal of an associated evolutionary parameter extraction procedure are reviewed. Both the model and the procedure are used to assess the effect of the annealing temperature on a nickel-1,4,8,11,15,18,22,25-octakis(hexyl)phthalocyanine (NiPc6)-based OTFT. A review of the importance of phthalocyanines in organic electronics is also provided. The characterization of the contact region in NiPc6 OTFTs complements the results extracted from other physical-chemical techniques such as differential scanning calorimetry or atomic force microscopy, in which the transition from crystal to columnar mesophase imposes a limit for the optimum performance of the annealed OTFTs.

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Cachexia and muscle wasting are very common among patients suffering from cancer, chronic obstructive pulmonary disease, and other chronic diseases. Ghrelin stimulates growth hormone secretion via the ghrelin receptor, which subsequently leads to increase of IGF-1 plasma levels. The activation of the GH/IGF-1 axis leads to an increase of muscle mass and functional capacity. Ghrelin further acts on inflammation, appetite, and adipogenesis and for this reason was considered an important target to address catabolic conditions. We report the synthesis and properties of an indane based series of ghrelin receptor full agonists; they have been shown to generate a sustained increase of IGF-1 levels in dog and have been thoroughly investigated with respect to their functional activity.

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This study reports methods for coating miniature implantable glucose biosensors with electrospun polyurethane (PU) membranes, their effects on sensor function and efficacy as mass-transport limiting membranes. For electrospinning fibres directly on sensor surface, both static and dynamic collector systems, were designed and tested. Optimum collector configurations were first ascertained by FEA modelling. Both static and dynamic collectors allowed complete covering of sensors, but it was the dynamic collector that produced uniform fibro-porous PU coatings around miniature ellipsoid biosensors. The coatings had random fibre orientation and their uniform thickness increased linearly with increasing electrospinning time. The effects of coatings having an even spread of submicron fibre diameters and sub-100 µm thicknesses on glucose biosensor function were investigated. Increasing thickness and fibre diameters caused a statistically insignificant decrease in sensor sensitivity for the tested electrospun coatings. The sensors' linearity for the glucose detection range of 2-30 mM remained unaffected. The electrospun coatings also functioned as mass-transport limiting membranes by significantly increasing the linearity, replacing traditional epoxy-PU outer coating. To conclude, electrospun coatings, having controllable fibro-porous structure and thicknesses, on miniature ellipsoid glucose biosensors were demonstrated to have minimal effect on pre-implantation sensitivity and also to have mass-transport limiting ability.

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A novel series of P2Y(12) antagonists for development of drugs within the antiplatelet area is presented. The synthesis of the piperazinyl-pyridine urea derivatives and their structure-activity relationships (SAR) are described. Several compounds showed P2Y(12) antagonistic activities in the sub-micromolar range.

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The detection sensitivity of silver nanoparticle (AgNP)-tagged goat immunoglobulin G (gIgG) microarrays was investigated by studying surface plasmon resonance (SPR) images captured in the visible wavelength range with the help of a Kretchmann-configured optical coupling set-up. The functionalization of anti-gIgG molecules on the AgNP surface was studied using transmission electron microscopy, photon correlation measurements and UV-visible absorption spectroscopy. A value of 1.3×10(7) M(-1) was obtained for the antibody-antigen binding constant by monitoring the binding events at a particular resonance wavelength. The detection limit of this SPR imaging instrument is 6.66 nM of gIgG achieved through signal enhancement by a factor of larger than 4 owing to nanoparticle tagging with the antibody.

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Solution-processed films of 1,4,8,11,15,18,22,25-octakis(hexyl) copper phthalocyanine (CuPc6) were utilized as an active semiconducting layer in the fabrication of organic field-effect transistors (OFETs) in the bottom-gate configurations using chemical vapour deposited silicon dioxide (SiO2) as gate dielectrics. The surface treatment of the gate dielectric with a self-assembled monolayer of octadecyltrichlorosilane (OTS) resulted in values of 4×10-2 cm2 V-1 s-1 and 106 for saturation mobility and on/off current ratio, respectively. This improvement was accompanied by a shift in the threshold voltage from 3 V for untreated devices to -2 V for OTS treated devices. The trap density at the interface between the gate dielectric and semiconductor decreased by about one order of magnitude after the surface treatment. The transistors with the OTS treated gate dielectrics were more stable over a 30-day period in air than untreated ones.

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This paper describes a heat transfer model based automatic secondary cooling system for a billet caster. The model aims to minimize the variation in surface temperature and excessive reheating of the billet strands. It is also used to avoid the low ductility trough of the solidifying steel, which aggravates the tendency of steel to crack. The system has been designed and implemented in an integrated steel plant. A Programmable Logic Controller (PLC) based automation system has been developed to control the water flow in the secondary cooling zones of the strand. The results obtained through field trials have shown complete elimination of internal and off-corner cracks for the fifty billet samples that were monitored.

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Optical absorption and Raman spectra of the sulfonated copper phthalocyanine (CuTsPc) layer were exploited for detection of cadmium (Cd) contaminants in water. Acetylcholine esterase was immobilized by freely suspending them in calcium alginate microbeads and this gel was then spincoated on the drop cast sulfonated copper phthalocyanine film on a glass substrate to form a bilayer. The inhibition of catalytic reaction between acetylcholine chloride and enzyme due to Cd contaminants was monitored by recording changes in spectra of drop cast CuTsPc as an indicator. The detection limit of cadmium content in water was found to be 1 ppm.

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A three layer waveguiding silicon dioxide (SiO(2))/silicon nitride (Si(3)N(4))/SiO(2) structure on silicon substrate was proposed as an optically efficient biosensor for calibration of heavy metal ions in drinking water. The catalytic activities of urease and acetylcholine esterase (AchE) were inhibited by the presence of cadmium (Cd(2+)) and lead (Pb(2+)) ions. The detection limit as low as 1 ppb was achieved by employing the technique of total reflection at the interface between the Si(3)N(4) core and composite polyelectrolyte self-assembled (PESA) membranes containing cyclotetrachromotropylene (CTCT) as an indicator.

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Generic hardwood mulch, usually used for landscaping, was utilized to remove several selected pollutants (heavy metals and toxic organic compounds) typically found in urban stormwater (SW) runoff. The hardwood mulch sorbed all the selected pollutants from a spiked stormwater mixture, including copper (Cu(2+)), cadmium (Cd(2+)), chromium (Cr(6+)), lead (Pb(2+)), zinc (Zn(2+)), 1,3 dichlorobenzene (DCB), naphthalene (NP), fluoranthene (FA), butylbenzylphthalate (BBP), and benzo(a)pyrene (B[a]P). Masses of the pollutants sorbed depended upon the pollutant species, contact time, and initial concentration which varied from 20 to 100%. Sorption rates of the metals, in general, were more rapid than those of the organics; however, mass removals (percent) of the organics, in contrast to those of the metals, were independent of their initial concentrations. With the exception of Cd, percentages (weight) of the metals removed declined as their initial concentrations decreased. None of the sorbed pollutants desorbed to any significant extent upon extended washing with water. It is quite feasible that in the presence of mulch the uptake of these pollutants by the aquatic species will be reduced significantly.

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Nanocrystalline cadmium sulphide thin films were prepared by the chemical bath (CB) deposition using a mixed aqueous solution of cadmium chloride, thiourea, and ammonium chloride. The XRD patterns showed that the CdS films were of hexagonal phase with preferred (002) orientation. From ellipsometric measurements, the film thickness was found to be in order of 66 nm and the optical band gap was estimated to be 2.4 eV.

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Heparin is a well established growth inhibitor of arterial smooth muscle cells (SMCs) both in animal models and in vitro. Even though the cellular mechanisms involved in the anti-proliferative properties of heparin are being resolved, the structural requirements for the biological effects of heparin are not known in detail. Here, we have studied the effect of chemically modified heparins of different molecular weights and anticoagulant activities on proliferation and adhesion of rat aortic SMCs in vitro. The effects of native heparin (NH) and chemically modified heparins were examined after stimulation with fetal calf serum (FCS), platelet-derived growth factor BB (PDGF BB), basic fibroblast growth factor (bFGF), and heparin-binding epidermal growth factor (hbEGF) with respect to DNA synthesis and expression of phosphorylated and activated mitogen-activated protein kinase (pERK1 and 2). In a similar manner as NH, the modified heparins were capable of inhibiting activation of ERK1 and 2 and DNA synthesis induced by FCS and hbEGF whereas the modified heparins potentiated the mitogenic effect of bFGF and no compound affected PDGF BB-induced ERK activity and SMC growth. In contrast, cell adhesion to fibronectin was inhibited by NH and modified heparins in a size-dependent manner with the lowest effect by the smallest compound. The results show that heparins with varying anticoagulant activities and molecular weights but with similar sulfate content can retain anti-proliferative properties while the effect on some other biological processes such as cell adhesion is lost. Possibly, such chemical alterations may yield useful substances for the prevention of SMC proliferation after arterial injury.

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o-Chloranil has been shown to form 1:1 molecular complexes with pyridine and 2-, 3- and 4-picolines in CCl4 medium. Isosbestic points have been found but charge-transfer bands could not be detected. The formation constants of the complexes exhibit a very good linear free energy relationship from which the Hammett p parameter for the complexation reaction is found to be -3.67.

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