2,3‐Dihydro‐1‐Benzofuran Derivatives as a Series of Potent Selective Cannabinoid Receptor 2 Agonists: Design,Synthesis, and Binding Mode Prediction through Ligand‐Steered Modeling

We recently discovered and reported a series of N‐alkyl‐isatin acylhydrazone derivatives that are potent cannabinoid receptor 2 (CB₂) agonists. In an effort to improve the druglike properties of these compounds and to better understand and improve the treatment of neuropathic pain, we designed and synthesized a new series of 2,3‐dihydro‐1‐benzofuran derivatives bearing an asymmetric carbon atom that behave as potent selective CB₂ agonists. We used a multidisciplinary medicinal chemistry approach with binding mode prediction through ligand‐steered modeling. Enantiomer separation and configuration assignment were carried out for the racemic mixture for the most selective compound, MDA7 (compound 18 ). It appeared that the S enantiomer, compound MDA104 (compound 33 ), was the active enantiomer. Compounds MDA42 (compound 19 ) and MDA39 (compound 30 ) were the most potent at CB₂. MDA42 was tested in a model of neuropathic pain and exhibited activity in the same range as that of MDA7. Preliminary ADMET studies for MDA7 were performed and did not reveal any problems.     

Crystal structure, magnetic and thermal properties of LaFeTeO6

LaFeTeO₆ was prepared by solid state reaction of La₂O₃, Fe₂O₃ and TeO₂ in 1:1:2 molar ratios and characterized by powder X-ray diffraction, thermogravimetry and magnetometry. The detailed crystal structure analysis was carried out by Rietveld refinement. LaFeTeO₆ crystallizes in a trigonal lattice with unit cell parameters: a = 5.2049(1) Å and c = 10.3457(2) Å, V = 242.73(2) Å³. The crystal structure is built from sheets of the edge shared FeO₆ and TeO₆ octahedra stacked along the c-axis. These sheets are connected together by La³⁺ ions. Thermogravimetric analysis of the compound showed it to be thermally stable up to 1323 K and continuous loss of TeO₂ was observed above 1323 K leading to the formation of LaFeO₃. High temperature XRD studies revealed a normal expansion behavior of the compound. Temperature and field dependent magnetization of LaFeTeO₆ showed paramagnetic behavior in the temperature range of 3-300 K. The effective magnetic moment per Fe³⁺ ion (5.14 μB) indicates the high spin d⁵ state of Fe³⁺ ion.     

Compositional effects on microstructure evolution and microwave properties of silver–palladium based thick film microstrips

Recent improvements in materials and processing technologies have dramatically increased the frequency range where ceramic thick film circuits can be utilized. Coupled with inherent advantages of thick film technology viz. low manufacturing cost, multilayering capability and relative insensitivity to substrate surface characteristics, such improvements have resulted in circuits that are penetrating the domain which was previously reserved to thin film technology. In view of newer developments in modern electronics, there is still ample scope for the development of new materials and processes especially in thick film technology. In thick films, conductors play a major role and silver–palladium is one of the important conductor materials in microelectronic circuits. Efforts are made in this work towards the development of suitable silver–palladium thick film conductors from the standpoint of microwave applications. The properties such as surface microstructure, sheet resistance, adhesion and microwave performance of the indigenously developed silver–palladium paste compositions is reported here. Highly porous surface structure, low adhesion and low characteristic impedance of thick film microstrip are observed for pastes with high palladium concentration.     

Optimum part orientation in Rapid Prototyping using genetic algorithm

Part orientation is an important parameter in the planning of a Rapid Prototyping (RP) process as it directly governs productivity, part quality and cost of manufacturing. This paper reports the design and implementation of a system for obtaining optimum orientation of a part for RP. Developed in a modular fashion, the system comprises of functional modules for CAD model preprocessing, shelling (hollowing), part orientation and optimization. CAD part model in STL format is an input to the system. The oriented CAD model is sliced and hollowed with desired shell thickness. Genetic algorithm based strategy is used to obtain optimum orientation of the parts for RP process. The objective criteria for optimization is considered to be a weighted average of the performance measures such as build time, part quality and the material used in the hollowed model. The developed system has been tested with several case studies considering SLS process.     

Compositional effects on microstructure evolution and microwave properties of silver–palladium based thick film microstrips

Recent improvements in materials and processing technologies have dramatically increased the frequency range where ceramic thick film circuits can be utilized. Coupled with inherent advantages of thick film technology viz. low manufacturing cost, multilayering capability and relative insensitivity to substrate surface characteristics, such improvements have resulted in circuits that are penetrating the domain which was previously reserved to thin film technology. In view of newer developments in modern electronics, there is still ample scope for the development of new materials and processes especially in thick film technology. In thick films, conductors play a major role and silver–palladium is one of the important conductor materials in microelectronic circuits. Efforts are made in this work towards the development of suitable silver–palladium thick film conductors from the standpoint of microwave applications. The properties such as surface microstructure, sheet resistance, adhesion and microwave performance of the indigenously developed silver–palladium paste compositions is reported here. Highly porous surface structure, low adhesion and low characteristic impedance of thick film microstrip are observed for pastes with high palladium concentration.     

Dispersion characteristics of optically excited coplanarstriplines: pulse propagation

The propagation of optically excited picosecond electrical pulses on coplanar striplines is analyzed. A full-wave analysis method that includes dispersion and losses over terahertz bandwidths is outlined. Results of the full-wave analysis are interpreted in terms of the underlying physical phenomena. The full-wave analysis reveals the existence of peaks in the dispersion curve of the coplanar stripline. These are interpreted in terms of the onset and coupling of the substrate modes to the transmission line mode. Results of the full-wave analysis are in good agreement with those obtained by established theory. Pulse propagation is simulated using the dispersion and loss data obtained from the analysis and accounts for all the relevant mechanisms. Results of simulations are compared with previously published experimental data for normal as well as superconducting lines. It is demonstrated that the superconducting phenomena are not dominant, whereas modal dispersion and substrate losses dominate the evolution of the output pulse and must be included for accurate modeling of pulse propagation on coplanar striplines     

Persistence of enterohemorrhagic Escherichia coli O157:H7 in soil and on leaf lettuce and parsley grown in fields treated with contaminated manure composts or irrigation water

Outbreaks of enterohemorrhagic Escherichia coli O157:H7 infections associated with lettuce and other leaf crops have occurred with increasing frequency in recent years. Contaminated manure and polluted irrigation water are probable vehicles for the pathogen in many outbreaks. In this study, the occurrence and persistence of E. coli O157:H7 in soil fertilized with contaminated poultry or bovine manure composts or treated with contaminated irrigation water and on lettuce and parsley grown on these soils under natural environmental conditions was determined. Twenty-five plots, each 1.8 by 4.6 m, were used for each crop, with five treatments (one without compost, three with each of the three composts, and one without compost but treated with contaminated water) and five replication plots for each treatment. Three different types of compost, PM-5 (poultry manure compost), 338 (dairy manure compost), and NVIRO-4 (alkaline-stabilized dairy manure compost), and irrigation water were inoculated with an avirulent strain of E. coli O157:H7. Pathogen concentrations were 10(7) CFU/g of compost and 10(5) CFU/ml of water. Contaminated compost was applied to soil in the field as a strip at 4.5 metric tons per hectare on the day before lettuce and parsley seedlings were transplanted in late October 2002. Contaminated irrigation water was applied only once on the plants as a treatment in five plots for each crop at the rate of 2 liters per plot 3 weeks after the seedlings were transplanted. E. coli O157:H7 persisted for 154 to 217 days in soils amended with contaminated composts and was detected on lettuce and parsley for up to 77 and 177 days, respectively, after seedlings were planted. Very little difference was observed in E. coli O157:H7 persistence based on compost type alone. E. coli O157:H7 persisted longer (by > 60 days) in soil covered with parsley plants than in soil from lettuce plots, which were bare after lettuce was harvested. In all cases, E. coli O157:H7 in soil, regardless of source or crop type, persisted for > 5 months after application of contaminated compost or irrigation water.     

Defect Simulation Methodology for iDDT Testing

The International Technology Roadmap for Semiconductors (ITRS) identifies two main challenges associated with the testing of manufactured ICs. First, the increase in complexity of semiconductor manufacturing process, physical properties of new materials, and the constraints imposed by resolution of lithography techniques etc., give rise to more complex failure mechanisms and hard-to-model defects that can no longer be abstracted using traditional fault models. Majority of defects, in today's technology, include resistive bridging and open defects with diverse electrical characteristics. Consequently, conventional fault models, and tools based on these models are becoming inadequate in addressing defects resulting from new failure mechanisms. Second, the defect detection resolution of main-stream I_DDQ testing is challenged by significant elevation in off-state quiescent current and process variability in newer technologies. Overcoming these challenges demands innovative test solutions that are based on realistic fault models capable of targeting real defects and thus, providing high defect coverage. In prior works power supply transient current or i_DDT testing has been shown to detect resistive bridging and open defects. The ability of transient currents to detect resistive opens and their insensitivity (virtually) to increase in static leakage current make i_DDT testing all the more attractive. However, in order to integrate i_DDT based methods into production test flows, it is necessary to develop a fault simulation strategy to assess the defect detection capability of test patterns and facilitate the ATPG process. The analog nature of the test observable, i.e., i_DDT signals, entail compute intensive transient simulations that are prohibitive. In this work, we propose a practical fault simulation model that partitions the task of simulating the DUT (device under test) into linear and non-linear components, comprising of power/ground-grid and core-logic, respectively. Using divide-and-conquer strategy, this model replaces the transient simulations of power/ground-grid with simple convolution operations utilizing its impulse response characteristics. We propose a path isolation strategy for core-logic as a means of reducing the computational complexity involved in deriving i_DDT signals in the non-linear portion. The methodology based on impulse response functions and isolated path simulation, can enable i_DDT fault simulation without having to simulate the entire DUT. To our knowledge, no practical technique exists to perform fault simulation for i_DDT based methods. The proposed fault simulation model offers two main advantages, first, it allows fault induction at geometric or layout level, thus providing a realistic representation of physical defects, and second, the current/voltage profile of power/ground-grid, derived for i_DDT fault simulation, can be used to perform accurate timing verification of logic circuit, thus facilitating design verification. In summary, the proposed fault simulation framework not only enables the assessment of defect detection capabilities of i_DDT test methodologies, but also establishes a platform for performing defect-based testing on practical designs.     

Phase study in Sr-Th-P-O system: Structural and thermal investigations of quaternary compounds

The sub-solidus phase relations in Sr-Th-P-O quaternary system were determined at 1223 K in air. To confirm the formation and stability of reported phases, ternary and quaternary compounds in Sr-Th-O, Sr-P-O, Th-P-O and Sr-Th-P-O systems were synthesized by solid state reactions of SrCO₃, ThO₂ and NH₄H₂PO₄ in desired molar proportions at 1223 K. A pseudo-ternary phase diagram of SrO-ThO₂-P₂O₅ system was drawn on the basis of the phase analysis of various phase mixtures and phase fields were established by powder X-ray diffraction. In the phase diagram, three quaternary compounds SrTh(PO₄)₂, SrTh₄(PO₄)₆ and Sr₇Th(PO₄)₆ were identified. When heated in air at 1673 K, these compounds decompose to ThO₂. Structures of SrTh(PO₄)₂, SrTh₄(PO₄)₆ and Sr₇Th(PO₄)₆ were derived from X-ray powder data using the Rietveld refinement method. Thermal expansion behaviors of SrTh(PO₄)₂, SrTh₄(PO₄)₆ and Sr₇Th(PO₄)₆ were investigated using high-temperature X-ray diffraction in the temperature range of 298-1273 K.