1-[2-(1-Cyclobutylpiperidin-4-yloxy)-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl]propan-1-one: a Histamine H3 Receptor Inverse Agonist with Efficacy in Animal Models of Cognition

A series of chemical optimizations, which was guided by in vitro affinity at histamine H₃ receptor (H₃R), modulation of lipophilicity, ADME properties and preclinical efficacy resulted in the identification of 1-[2-(1-cyclobutylpiperidin-4-yloxy)-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl]propan-1-one ( 45 e ) as a potent and selective (K_i=4.0 nM) H₃R inverse agonist. Dipsogenia induced by (R)-α-methylhistamine was dose dependently antagonized by 45 e , confirming its functional antagonism at H₃R. It is devoid of hERG and phospholipidosis issues. Compound 45 e has adequate oral exposures and favorable half-life in both rats and dogs. It has demonstrated high receptor occupancy (ED₈₀=0.22 mg/kg) and robust efficacy in object recognition task and, dose dependently increased acetylcholine levels in brain. The sub-therapeutic doses of 45 e in combination with donepezil significantly increased acetylcholine levels. The potent affinity, selectivity, in vivo efficacy and drug like properties together with safety, warrant for further development of this molecule for potential treatment of cognitive disorders associated with Alzheimer's disease.     

Continued self-similar breakup of drops in viscous continuous phase in agitated vessels

Drop breakup in viscous liquids in agitated vessels occurs in elongational flow around impeller blade edges. The drop size distributions measured over extended periods for impellers of different sizes show that breakup process continues up to 15–20 h, before a steady state is reached. The size distributions evolve in a self-similar way till the steady state is reached. The scaled size distributions vary with impeller size and impeller speed, in contrast with the near universal scaling known for drop breakup in turbulent flows. The steady state size of the largest drop follows inverse scaling with impeller tip velocity. The breadth of the scaled size distributions also shows a monotonic relationship with impeller tip velocity only.     

A reduced reaction model for carbon CVD/CVI processes

Carbon-carbon composites are produced by chemical vapor deposition/chemical vapor infiltration (CVD/CVI) processes. Models of carbon-carbon composite production processes will help reduce production costs. Reliable process models must, however, include details of the gas phase kinetics in order to identify optimal conditions. We have combined detailed gas phase kinetics, surface kinetics, and a pore closure model to predict pore geometry changes with respect to time. To determine the dominant gas phase kinetics, we reduced a large set of reactions to a minimal set using a sensitivity, rate, and dimensional analysis approach. These robust and relatively fast techniques can be used under a variety of conditions, including those within the pores of the composite. The process model shows that the deposition profile depends on the kinetic model chosen. Using the more realistic reaction model, conditions for uniform, or inside-out, densification can be suggested.     

Kinetics of the hydroformylation of soybean oil by ligand-modified homogeneous rhodium catalysis

The kinetics and mechanism of the hydroformylation of soybean oil by homogeneous ligand-modified rhodium catalysts were investigated at 70–130°C and 4000–11,000 kPa. The effects of reaction rates on systematic variations in reaction parameters were evaluated in order to develop an industrial process to convert vegetable oils to polyaldehydes. The activation energies in the presence of triphenylphosphine (Ph₃P) (61.1±0.8 kJ/mol) (mean±SD) and triphenyl phosphite [(PhO)₃P] (77.4±5.0 kJ/mol) were determined. The catalyst was deactivated at temperatures higher than 100°C. An evaluation of the effects of the reaction parameters on initial rates yielded the rate laws for Ph₃P {rate=k [olefin][Rh(CO)₂Acac]^1.1 [Ph₃P]^−0.5 (pH₂+pCO)^1.4, where Rh(CO)₂Acac is (acetylacetonato)dicarbonylrhodium (I)} and (PhO)₃P {rate=[olefin] [Rh(CO)₂Acac]^1.2 [(PhO)₃P]^−0.8 (pH₂+pCO)^0.9 at total pressures lower than 7000 kPa, and rate =[olefin] [Rh(CO)₂Acac]^1.2 [(PhO)₃P]^−0.8(pH₂+pCO)^1.7 at total pressures higher than 7000 kPa}.     

Effect of Tween-80 on the Control of Particle Size and Shrinkage Properties of Nanoscale α-Alumina Synthesized by Sol–Gel Processing

The concept of tailored interfaces has been applied to the synthesis of nanoscale α-Al₂O₃. Tween-80 (poly-oxyethylene(20) sorbitan monooleate, T-80) was used as a surface modifier in the sol–gel process for this purpose. High-resolution transmission electron microscopy study of the powder obtained with T-80 confirmed the particle size of α-Al₂O₃ (∼55 nm) and morphology (spherical). The exothermic peak temperature in the differential thermal analysis was shifted to a lower temperature (∼917°C) when the powder was derived from a T-80 modifier content of 10 wt%. X-ray diffraction showed that the α-Al₂O₃ phase was the major phase that existed in modifier-derived powder that was sintered at 1000°C. The experiments, based on linear shrinkage, indicated that the powder with T-80 (10 wt%) could be densified at a low temperature.     

Development of LTCC micro-hotplate with PTC temperature sensor for gas-sensing applications

Low temperature co-fired ceramic (LTCC) micro-hotplates show wide applications in gas sensors and micro-fluidic devices. It is easily structured in three-dimensional structures. This paper presents the low power consumption micro-hotplates which were developed with PTC (positive temperature coefficient) temperature sensor and inter-digitated electrodes. The paper presents two different structures for micro-hotplate with platinum as a heating element. The PTC temperature sensor using two different materials viz. PdAg and platinum paste are developed with micro-hotplates. The simulation has been achieved through COMSOL for LTCC and alumina micro-hotplates. The temperature variation with power consumption has been measured for the developed LTCC micro-hotplates. The change in resistance of PTC temperature sensors was measured with micro-hotplate temperature. The aim of this study was to place a temperature sensor with the gas sensor module to measure and control the temperature of micro-hotplate. A SnO₂ sensing layer is coated on LTCC micro-hotplate using screen printing and characterized for the sensing of carbon monoxide gas (CO). This study will be beneficial for designing hotplates based on LTCC technology with low power consumption and better stability of temperature for gas-sensing applications.     

Spray dryer processed graphene oxide/reduced graphene oxide for high-performance supercapacitor

This study deals with the utility of mini spray dryer process to improve the dispersibility, of graphene oxide(GO) and its application for high-performance supercapacitor. Initially, the neutral solution of GO was obtained using the modified Hummer's method. After this, the prepared GO solution was processed by mini spray dryer to obtain a more purified, lighter, and dispersed form of GO which is named as spray dryer processed GO (SPGO). The SPGO thus obtained showed excellent dispersibility behavior with various solvents, which is not found in case of conventional oven drying. Furthermore, utility of SPGO and its reduced form (r-SPGO) for supercapacitor applications have been investigated. Results obtained from the cyclic voltammetry(CV) analysis, impedance, and charge-discharge behavior of supercapacitor fabricated using r-SPGO shows enhanced features. Therefore, the simple spray dried GO and its reduced form, that is, r-SPGO can be utilized as a potential candidate for the supercapacitor application. Herein, as synthesized SPGO exhibited the specific capacitance of 12.07 and 37.6 F/g with PVA-H₃PO₄ and 1 mol/L H₃PO₄, respectively, at a scan rate of 5 mV/s. On the other hand, reduced form of SPGO, that is, r-SPGO showed the specific capacitance of 27.16 and 230 F/g with PVA-H₃PO₄ and 1 mol/L H₃PO₄, respectively.     

Effects of V2O5 addition on the corrosion resistance of andalusite-based low-cement castables with molten Al-alloy

Interfacial reactions between Al-alloy and andalusite low-cement castables (LCC) containing 5 wt% V₂O₅ were analyzed at 850 °C and 1160 °C using the Alcoa cup test. Interfacial reaction products and phases formed during heat treatment of the refractory samples were characterized using scanning electron microscopy (SEM) coupled with energy dispersive spectrometry (EDS) and X-ray diffraction (XRD) analysis. V₂O₅ addition resulted in the formation of glassy phases, which significantly improved the corrosion resistance. These phases were preferentially corroded by the alloy, due to their glassy nature. However, vanadium formed from reduction, formed intermetallic alloys (V–Al–Si–Mg), which formed an interfacial physical barrier to further alloy penetration.     

Interfacial Reactions Between BaAl2Si2O8 and Molten Al Alloy at 850°C

A corrosion cup test was undertaken using BaAl₂Si₂O₈ and Al4.1Zn3.2Mg alloy, heated in air for 150 h at 850°C. Electron probe microanalysis, X‐ray diffraction, and scanning electron microscopy coupled with energy dispersive spectroscopy were used to identify the mineralogical and microstructural changes at the interfaces. The microstructural results revealed three microstructural areas: (1) Spinel layer with large numbers of Al alloy channels; (2) interfacial area with mainly alumina, spinel, and BaAl₂Si₂O₈; and (3) interdiffusion zone chemically close to barium hexaaluminate. The principal observations are:

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Lipoxygenase and Tocopherol Profiling of Soybean Genotypes Exposed to Electron Beam Irradiation

Electron beam (EB)-irradiation is increasingly being preferred to radioactive-based gamma irradiation in overcoming the constraints that affect the quality of food material. Soybean seeds of 3 soybean genotypes were exposed to 4 doses viz. 4.8, 9.2, 15.3 and 21.2 kGy of EB-irradiation and assessed for the changes in the contents of lipoxygenase isozymes and tocopherol isomers. Densitometry of protein profile revealed decreasing intensity of lipoxygenase with increasing EB dose. All the 3 lipoxygenase isozymes viz. lipoxygenase-1, -2 and -3 registered significant (P < 0.05) increasing reduction with increasing dose; though genotypic variation was noted for the magnitude of reduction at the same dose. Concomitantly, all the 3 genotypes exhibited significant (P < 0.05) decline in α-, γ- and δ-isomers of tocopherol. δ-Tocopherol was the most sensitive to EB-irradiation. EB dose, which caused minimum and maximum decline in total tocopherol content, was genotype-dependent. Decline in vitamin E activity corresponding to the dose, which induced maximum reduction for total lipoxygenase also varied in 3 genotypes. The study showed the usefulness of EB for significant inactivation of off-flavor generating lipoxygenases in soybean, with a non-significant effect on oil content and varied retention of tocopherol isomers and vitamin E activity depending upon genotype.