Design,optimization and evaluation of poly-ɛ-caprolactone (PCL) based polymeric nanoparticles for oral delivery of lopinavir

Lopinavir (LPV)-loaded poly-ε-caprolactone (PCL) nanoparticles (NPs) were prepared by emulsion solvent evaporation technique. Effects of various critical factors in preparation of loaded NPs were investigated. Box–Behnken design (BBD) was employed to optimize particle size and entrapment efficiency (EE) of loaded NPs. Optimized LPV NPs exhibited nanometeric size (195.3?nm) with high EE (93.9%). In vitro drug release study showed bi-phasic sustained release behavior of LPV from NPs. Pharmacokinetic study results in male Wistar rats indicated an increase in oral bioavailability of LPV by 4-folds after incorporation into PCL NPs. From tissue distribution studies, significant accumulation of loaded NPs in tissues like liver and spleen indicated possible involvement of lymphatic route in absorption of NPs. Mechanistic studies using rat everted gut sac model revealed endocytosis as a principal mechanism of NPs uptake. In vitro rat microsomal metabolism studies demonstrated noticeable advantage of LPV NPs by affording metabolic protection to LPV. These studies indicate usefulness of PCL NPs in enhancing oral bioavailability and improving pharmacokinetic profile of LPV.     

Unsteady wake dynamics and heat transfer in forced and mixed convection past a circular cylinder in cross flow for high Prandtl numbers

This paper investigates the combined effect of Prandtl number and Richardson number on the wake dynamics and heat transfer past a circular cylinder in crossflow using a SUPG based finite element method. The computations are carried out for 80 < Re < 180, 0.7 < Pr < 100 and $0?\mathrm{Ri}?2$. The results have been presented for both forced and mixed convection flows. In the case of forced convection, crowding of temperature contours with reduced spatial spread is observed for increasing Prandtl numbers. The local and average Nusselt numbers are found to increase with increasing Reynolds number and Prandtl number. The average Nusselt number and Colburn factor are found to vary as Re^0.548 Pr ^0.373 and Re^?0.452, respectively. The extrapolated results of the average Nusselt number for low and high Reynolds numbers are found to match quite well with the available results in literature. Effect of Prandtl number shows various interesting phenomena for the mixed convective flows. Increasing the Prandtl numbers resulted in decreasing deflection and strength in the wake structures. The effect of baroclinic vorticity production during vortex shedding has been demonstrated at the vicinity of the cylinder and near wake. The Strouhal number is found to decrease with increasing Prandtl number, in the case of buoyancy induced flow. The effect of increasing Prandtl number is manifested as the stabilizing effect in the flow. This is, perhaps, the first time that such behavior for the Prandtl number is being reported. Additionally it is observed that the average Nusselt number decreases with increasing Richardson number.     

Manganese dioxide — a review of a battery chemical Part II. Solid state and electrochemical properties of manganese dioxides

A literature survey indicated that the properties such as electrical conductivity, magnetic susceptibility, thermal decomposition temperature and water content influence the activity of manganese dioxides.Infrared spectroscopy is considered as a convenient analytical tool with which to characterize the various crystal phases of the dioxides. Increasing attention has also been given to predicting the potentials of the system (MnO₂)_1?r. MnOOH_r during electrochemical reduction with a view to understanding the observed discharge characteristics.Further, attempts are being made to correlate the activity of the dioxides with their structural features.     

Association of insulin resistance to electrocardiographic changes in non obese Asian Indian subjects with hypertension

Although it is well documented that child maltreatment exerts a deleterious impact on child adaptation, much less is known about the precise etiological pathways that eventuate in child abuse and neglect. This paper reports on a multimethod ecological study of the relationship between neighborhood structural factors and child maltreatment reports in African American and European American census tracts. The study had two major components. First, in an aggregate analysis, the effects of four measures of community structure (impoverishment, child care burden, instability, and geographic isolation) on child maltreatment report rates were examined separately for predominantly African American (n = 94) and predominantly European American (n = 189) census tracts. Impoverishment in particular had a significantly weaker effect on maltreatment rates in African American than in European American neighborhoods. Second, focused ethnographies were conducted in four selected census tracts with child maltreatment report rates in the highest and lowest quartiles. Ethnographic data point to the importance of the social fabric in accounting for differences in child maltreatment report rates by predominant neighborhood ethnicity.     

Effects of the inclination angle on natural convection heat transfer and entropy generation in a square porous enclosure

ABSTRACT

In this paper, we analyze numerically the effects of the inclination angle on natural convection heat transfer and entropy generation characteristics in a two-dimensional square enclosure saturated with a porous medium. There is a significant alteration in Nusselt number with the orientation of the enclosure at higher values of Rayleigh number. It reveals that the variation of entropy generation rate with the inclination angle is significant for higher values of Darcy number. The dominant source of irreversibility is due to heat transfer at low values of Darcy number, whereas entropy generation due to fluid flow dominates over that due to heat transfer for larger values of Darcy number.     

Factor-Covering Designs for Testing Software

Testing is a critical component of modern software development. The problem of designing a suite of test cases is superficially similar to that of designing an experiment to estimate main effects and interactions, but there are crucial differences. Additive models are unhelpful, and classical design criteria are also. We propose a new class of models and new measures of effectiveness. We compare several designs.     

How to improve performance of software systems: A methodology and a case study for tuning performance

Before software systems are shipped, they are tuned to optimize their field performance. This process is called performance tuning. Performance tuning is used to find the best settings for a set of tunable, or changeable, parameters like buffer space, disk file allocation, main memory partition, I/O priority, process scheduling quantum, etc. Examples of performance measures to be optimized are: query or transaction loss, throughput rate, response time, etc. Improperly tuned systems can create field problems even if there are no software faults in the product. Hence, it is important that software systems be tuned for optimal performance before they are delivered. However, optimal performance tuning is quite complex because of: exponentially many alternatives, unknown functional relationships between parameters and performance measures, stochastically fluctuating system performance, and expensive empirical experiments. For these reasons, tuning is typically practiced as an art and depends heavily on the intuitions of experts. In this paper, we examine a method for tuning which is repeatable and produces consistently superior results across many different applications. This method, based upon Robust Experimental Design, has revolutionized design optimization in hardware systems. The methodology consists of conducting a few carefully chosen experiments and using the associated analysis technology to help extract the maximum possible information for performance optimization. Specifically we give some background on statistical experimental design and demonstrate it on an actual software system that provides network database services which had experienced occasional query losses. Focusing on nine carefully chosen parameters, 12 experiments were conducted. This number of experiments is far fewer and consequently far less costly in time and effort than what would be required for collecting the same amount of information by traditional methods. The selection of the experiments took into account ideas from accelerated life testing and ideas from the Robust Experimental Design. Based on the analysis of this data, new settings for the parameters in software system were implemented. All tests done with the new settings have shown that the query loss problem has been totally controlled. This revised version was published online in June 2006 with corrections to the Cover Date.     

Power spectral analysis of heart period variability of preceding sinus rhythm before initiation of paroxysmal atrial fibrillation

Time domain analysis of heart period variability in patients without structural heart disease demonstrated increased parasympathetic modulation before paroxysmal atrial fibrillation (AF) occurring predominantly at night. However, diurnal differences in autonomic activity preceding AF episodes in a diverse patient population have not been assessed. Accordingly, we performed spectral analysis of heart period variability on Holter recordings during sinus rhythm preceding AF in 29 patients, 17 with night and 12 with day episodes. Samples taken 5, 10, and 20 minutes before AF onset were compared. Normalized high-frequency (HF) spectral power change was greater when comparing the interval 10 to 5 minutes with 20 to 10 minutes preceding AF in 26 of 29 patients (0.09 +/- 0.07 vs 0.03 +/- 0.02; p < 0.0001). HF spectral power increased before 3 of 12 AF episodes during the day compared with 15 of 17 AF episodes during the night (p = 0.001). Nocturnal AF episodes were preceded by increased HF spectral power in the 5- versus the 20-minute sample expressed as natural logarithm-transformed values (5.6 +/- 4.8 vs 4.2 +/- 4.0; p < 0.005) and normalized values (0.19 +/- 0.09 vs 0.10 +/- 0.07; p < 0.02), a decrease in low-frequency/HF ratio (1.05 +/- 0.61 vs 2.21 +/- 1.75; p < 0.05) and heart rate (60 +/- 13 vs 71 +/- 13 beats/min; p = 0.06). Structural heart disease was more common with daytime than nocturnal AF episodes (58% vs 18%, p < 0.05). In conclusion, HF spectral power change was increased preceding most AF episodes. However, diurnal differences were demonstrated. Contrary to daytime AF, increased parasympathetic activity preceded predominantly nocturnal AF, mostly in younger patients with structurally normal hearts.