Fluorine in Drug Design: A Case Study with Fluoroanisoles

Anisole and fluoroanisoles display distinct conformational preferences, as evident from a survey of their crystal structures. In addition to altering the free ligand conformation, various degrees of fluorination have a strong impact on physicochemical and pharmacokinetic properties. Analysis of anisole and fluoroanisole matched molecular pairs in the Pfizer corporate database reveals interesting trends: 1) PhOCF₃ increases log D by ～1 log unit over PhOCH₃ compounds; 2) PhOCF₃ shows lower passive permeability despite its higher lipophilicity; and 3) PhOCF₃ does not appreciably improve metabolic stability over PhOCH₃. Emerging from the investigation, difluoroanisole (PhOCF₂H) strikes a better balance of properties with noticeable advantages of log D and transcellular permeability over PhOCF₃. Synthetic assessment illustrates that the routes to access difluoroanisoles are often more straightforward than those for trifluoroanisoles. Whereas replacing PhOCH₃ with PhOCF₃ is a common tactic to optimize ADME properties, our analysis suggests PhOCF₂H may be a more attractive alternative, and greater exploitation of this motif is recommended.     

Analysis of pulsatile flow and its role on particle removal from surfaces

The use of pulsatile flow for energy efficient particle removal from surfaces is evaluated through modeling calculations. The governing equation for pulsatile flow in a channel between parallel plates with an oscillatory pressure input is solved and wall shear stress, identified as a measure for particle removal, calculated for fixed power input. It is observed that as the frequency of oscillation is increased the average wall shear stress with an oscillatory pressure input is higher than the corresponding steady state value only above a critical frequency. Similar results are obtained for pulsatile flow in a pipe. Explanation for this observation is presented based on how velocity profile changes as a function of frequency and consequently its effect on wall shear stress versus power dissipated. Based on these observations we propose that there is a critical frequency above which an oscillatory pressure input will be energy efficient for particle removal.     

Using Stochastic Differential Equation for Verification of Noise in Analog/RF Circuits

Today’s analog/RF design and verification face significant challenges due to circuit complexity, process variations and short market windows. In particular, the influence of technology parameters on circuits, and the issues related to noise modeling and verification still remain a priority for many applications. Noise could be due to unwanted interaction between the circuit elements or it could be inherited from the circuit elements. In addition, manufacturing disparity influence the characteristic behavior of the manufactured circuits. In this paper, we propose a methodology for modeling and verification of analog/RF designs in the presence of noise and process variations. Our approach is based on modeling the designs using stochastic differential equations (SDE) that will allow us to incorporate the statistical nature of noise. We also integrate the device variation due to 0.18μ m fabrication process in an SDE based simulation framework for monitoring properties of interest in order to quickly detect errors. Our approach is illustrated on nonlinear Tunnel-Diode and a Colpitts oscillator circuits.     

Total Power Optimization for Combinational Logic Using Genetic Algorithms

Power consumption is a top priority in high performance circuit design today. Many low power techniques have been proposed to tackle the ever serious, highly pressing power consumption problem, which is composed of both dynamic and static power in the nanometer era. The static power consumption nowadays receives even more attention than that of dynamic power consumption when technology scales below 100 nm. In order to mitigate the aggressive power consumption, various existing low power techniques are often used; however, they are often applied independently or combined with two or at most three different techniques together, and that is not sufficient to address the escalating power issue. In this paper, we present a power optimization framework for the minimization of total power consumption in combinational logic through multiple V _dd assignment, multiple V _th assignment, device sizing, and stack forcing, while maintaining performance requirements. These four power reduction techniques are properly encoded into the genetic algorithm and evaluated simultaneously. The overhead imposed by the insertion of level converters is also taken into account. The effectiveness of each power reduction mechanism is verified, as are the combinations of different approaches. Experimental results are presented for a number of 65 nm benchmark circuits that span typical circuit topologies, including inverter chains, SRAM decoders, multiplier, and a 32 bit carry adder. Our experiments show that the combination of four low power techniques is the effective way to achieve low power budget. The framework is general and can be easily extended to include other design-time low power techniques, such as multiple gate length or multiple gate oxide thickness.     

Development and Integration of Sub-hourly Rainfall–Runoff Modeling Capability Within a Watershed Model

Increasing urbanization changes runoff patterns to be flashy and instantaneous with decreased base flow. A model with the ability to simulate sub-daily rainfall–runoff processes and continuous simulation capability is required to realistically capture the long-term flow and water quality trends in watersheds that are experiencing urbanization. Soil and Water Assessment Tool (SWAT) has been widely used in hydrologic and nonpoint sources modeling. However, its subdaily modeling capability is limited to hourly flow simulation. This paper presents the development and testing of a sub-hourly rainfall–runoff model in SWAT. SWAT algorithms for infiltration, surface runoff, flow routing, impoundments, and lagging of surface runoff have been modified to allow flow simulations with a sub-hourly time interval as small as one minute. Evapotranspiration, soil water contents, base flow, and lateral flow are estimated on a daily basis and distributed equally for each time step. The sub-hourly routines were tested on a 1.9 km² watershed (70% undeveloped) near Lost Creek in Austin Texas USA. Sensitivity analysis shows that channel flow parameters are more sensitive in sub-hourly simulations (Δt = 15 min) while base flow parameters are more important in daily simulations (Δt = 1 day). A case study shows that the sub-hourly SWAT model reasonably reproduces stream flow hydrograph under multiple storm events. Calibrated stream flow for 1 year period with 15 min simulation (R ² = 0.93) shows better performance compared to daily simulation for the same period (R ² = 0.72). A statistical analysis shows that the improvement in the model performance with sub-hourly time interval is mostly due to the improvement in predicting high flows. The sub-hourly version of SWAT is a promising tool for hydrology and non-point source pollution assessment studies, although more development on water quality modeling is still needed.     

Impact of volume fraction and fluid layer thickness on heat transfer effectiveness of water-based nanofluids

The heat transfer effectiveness of nanofluids is adversely affected by the delay in convection onset. The lesser effectiveness, when compared to that of base fluid, is observed in a range of nanofluid layer thickness. The heat transfer coefficient of water–Al₂O₃ nanofluid can be enhanced by sustaining the equilibrium between Rayleigh number, temperature, particle volume fraction, and enclosure aspect ratio. In this paper, the specific correlation of fluid layer thickness and the onset of convection, which can significantly dominate the heat transfer characteristics of nanofluids are investigated using the concept of critical Rayleigh number. The water layer thickness for convection onset is first experimentally assessed for different real-life heat flux densities. It is then performed for Al₂O₃–water nanofluid for varying volume fractions. With the increase in volume fraction even though thermal conductivity increases, the overall heat transfer enhancement of the nanofluid is reduced. Temperature involved (heat flux density), the volume fraction of the nanofluid used, nanofluid layer thickness (space availability for the cooling system), and mass of the nanoparticle influence heat transfer enhancement. A higher volume fraction may not always result in enhancement of heat transfer as far as nanofluids are concerned.     

Effect of Thermal Oxidation on Corrosion Resistance of Commercially Pure Titanium in Acid Medium

This article addresses the characteristics of commercially pure titanium (CP-Ti) subjected to thermal oxidation in air at 650?°C for 48?h and its corrosion behavior in 0.1 and 4?M HCl and HNO₃ mediums. Thermal oxidation of CP-Ti leads to the formation of thick oxide scales (~20???m) throughout its surface without any spallation. The oxide layer consists of rutile- and oxygen-diffused titanium as predominant phases with a hardness of 679?±?43?HV_1.96. Electrochemical studies reveal that the thermally oxidized CP-Ti offers a better corrosion resistance than its untreated counterpart in both HCl and HNO₃ mediums. The uniform surface coverage and compactness of the oxide layer provide an effective barrier toward corrosion of CP-Ti. The study concludes that thermal oxidation is an effective approach to engineer the surface of CP-Ti so as to increase its corrosion resistance in HCl and HNO₃ mediums.     

A wide-ranging review on Nasicon type materials

Nasicons (sodium super ion conductors) are a class of solid electrolytes. Their structure, compositional diversity, evolution, and applications are reviewed. A wide range of materials is considered based on crystalline and glassy Nasicon compositions.     

Unequal packet loss resilience for fine-granular-scalability video

Several embedded video coding schemes have been recently developed for multimedia streaming over IP. In particular, fine-granular-scalability (FGS) video coding has been recently adopted by the MPEG-4 standard as the core video-compression method for streaming applications. From its inception, the FGS scalability structure was designed to be packet-loss resilient especially under unequal packet-loss protection (UPP). However, since the introduction of FGS, there has not been a comprehensive study evaluating its packet-loss resilience under unrecoverable packet losses that are common in Internet streaming applications. In this paper, we evaluate two important aspects of FGS packet-loss resilience. First, we study the impact of applying UPP between the base- and enhancement-layers on FGS-based streams, and we compare equal packet-loss protection (EPP) with UPP scenarios. Second, we introduce the notion of fine-grained loss protection (FGLP), which is suitable for the FGS enhancement-layer, and we develop an analytical framework for evaluating FGLP bounds. Based on these bounds, we show the impact of applying fine-grained protection to the FGS enhancement-layer for different types of video sequences and over a wide range of bit-rates and packet-loss ratios. As illustrated by our extensive simulation results, applying 1) UPP between the base- and enhancement-layers and 2) FGLP for the FGS enhancement-layer can provide significant resilience under moderate-to-high packet-loss ratios (e.g., 5-10%). Furthermore, the merits of this new packet-loss protection technique go beyond the FGS coding scheme, because FGLP can be successfully applied to improve the resilience to packet-losses of other embedded video coding techniques     

CdO nanoparticles,c‐MWCNT nanoparticles and CdO nanoparticles/c‐MWCNT nanocomposite fibres: in vitro assessment of anti‐proliferative and apoptotic studies in HeLa cancer cell line

A simple ultrasonic assisted chemical technique was used to synthesise cadmium oxide (CdO) nanoparticles (NPs) and CdO NPs/c‐Multiwalled carbon nanotube (c‐MWCNT) nanocomposite fibres.To confirm the physio‐chemico properties and to analyse surface morphology of the obtained nanomaterials X‐Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) and field emission scanning electron microscopy (FESEM) were performed. To evaluate the anti‐cancer property of CdO NPs, c‐MWCNT NPs and CdO NPs/c‐MWCNT nanocomposite fibres, an anti‐proliferative assay test (Methylthiazolyl diphenyl‐ tetrazolium bromide ‐ MTT assay) were performed on HeLa cells which further estimated IC50 value (Least concentration of sample in which nearly 50% of cells remain alive) under in‐vitro conditions. On comparison, CdONPs/c‐MWCNT based system was found to be superior by achieving 52.3% cell viability with its minimal IC50 value of 31.2 μg/ml. Lastly, the CdO NPs based system was taken up for an apoptotic study using DNA fragmentation assay for estimating its ability to cleave the DNA of the HeLa cells into internucleosomal fragments using the agarose gel electrophoresis method. In conclusion, based on our observations, CdO NPs/c‐MWCNT hybrid based system can be further used for the development of efficient drug delivery and therapeutic systems.Inspec keywords: drug delivery systems, electrophoresis, oxidation, toxicology, DNA, nanoparticles, drugs, field emission electron microscopy, scanning electron microscopy, nanofabrication, surface morphology, cancer, X‐ray diffraction, nanomedicine, cellular biophysics, filled polymers, biomedical materials, molecular biophysics, biochemistry, Fourier transform infrared spectra, multi‐wall carbon nanotubesOther keywords: c‐MWCNT nanoparticles, apoptotic study, HeLa cancer cell line, cadmium oxide nanoparticles, c‐MWCNT NPs, anti‐proliferative assay test [methyl thiazolyl diphenyl‐tetrazolium bromide assay], human epithelioid cervix carcinoma cells, live cells, CdO NP‐based system, IC50 concentration, HeLa cell line, cell deaths, CdO‐C