Drug-induced hepatotoxicity studied in a 3D, in vitro model of the liver

Drug development is a high failure rate process; too many drugs fail during clinical trials because of severe hepatotoxicity. This situation can be significantly improved by redesigning preclinical trials, and privileging the use of high-throughput in vitro models, by combining cell-based in vitro models and material-based models.

The dorsolateral prefrontal cortex reflects the impact of anxiety on drift rates during cognitive processing

Generally, anxiety is thought to impair ongoing cognitive operations. Surprisingly, however, anxiety has been shown to improve performance during the Go/No-Go task. Understanding how anxiety can facilitate task performance may shed light on avenues to address the cognitive deficits commonly associated with anxiety. Here, we set out to identify the computational processes and neural mechanisms underlying the impact of anxiety on Go/No-Go task performance using a combination of computational drift diffusion models and ultra-high field (7T) functional MRI. Hierarchical Bayesian analysis suggest that anxiety, induced using the delivery of unpredictable electrical shock, was associated with a higher drift rate process which is thought to reflect increased informational uptake. Additionally, changes in drift rate during the anxiety condition were associated with enhanced BOLD responses within the dorsolateral prefrontal cortex and posterior cingulate cortex during No-Go trials. This relationship may reflect the impact of induced anxiety on the activity of ramping neurons within the dorsolateral prefrontal cortex, whose activity patterns mimic the drift rate process. Collectively, these results shed light on the mechanisms underlying facilitated task performance and suggest that anxiety can improve cognitive processing by enhancing information uptake and increasing activity within prefrontal and posterior cingulate cortices.

Generalized Fractional Calculus for Gompertz-Type Models

This paper focuses on the construction of deterministic and stochastic extensions of the Gompertz curve by means of generalized fractional derivatives induced by complete Bernstein functions. Precisely, we first introduce a class of linear stochastic equations involving a generalized fractional integral and we study the properties of its solutions. This is done by proving the existence and uniqueness of Gaussian solutions of such equations via a fixed point argument and then by showing that, under suitable conditions, the expected value of the solution solves a generalized fractional linear equation. Regularity of the absolute p-moment functions is proved by using generalized Grönwall inequalities. Deterministic generalized fractional Gompertz curves are introduced by means of Caputo-type generalized fractional derivatives, possibly with respect to other functions. Their stochastic counterparts are then constructed by using the previously considered integral equations to define a rate process and a generalization of lognormal distributions to ensure that the median of the newly constructed process coincides with the deterministic curve.

Prediction and Estimation of Electroplating Characteristics, Corrosion Rate of Zinc Coated Mild Steel Coupling

This present research work is taken to estimate the corrosion rate of zinc coated mild steel coupling with using of Design of Experiments (DOE). Now a day’s mild steel materials are simply corroded in the all medium including atmospheric conditions. Overcome of this planed to applying the zinc coating on the mild steel material. In this study considered of normal use of mild steel coupling for the industrial applications. Main goal of this study to evaluate the Coating thickness (µm), Change of mass (g) and Corrosion rate (mm/y) of the coupling after coating. The L16 Orthogonal array of Taguchi analysis is engaged to find the response values. The different process parameters are considered for to analysis of electroplating characteristics, corrosion rate. Process parameters are namely current density (0.3 amps/ dm2,0.5 amps/ dm2,0.7 amps/ dm2 and 0.9 amps/ dm2), concentration of Zinc (10 g/L, 12 g/L, 14 g/L and 16 g/L), coating time (45 min, 60 min, 75 min and 90 min) and temperature (20 oC, 30 oC, 40 oC and 50 oC).

Pharmacokinetic Appraisal of Carprofen Delivery from Intra-Articular Nanoparticles: A Population Modeling Approach in Rabbits

Osteoarthritis is frequently treated in veterinary settings with non-steroidal anti-inflammatory drugs (NSAID) such as carprofen (CP). Its action over the articular cartilage can be enhanced by increasing drug uptake into the cartilage, alongside its site of action, and anticipating its rapid distribution towards the bloodstream. A pharmacokinetic study to evaluate carprofen nanoparticles (NP) after intraarticular administration (IA) in rabbits was performed through a modeling allometric approach. The pharmacokinetic analysis of plasma profiles showed a rapid CP distribution outwards the synovial chamber but mainly remaining in plasma (Vc = 0.14 L/5 Kg), according to its high protein-binding. The absorption data modeling showed the occurrence of two different release–absorption rate processes after nanoparticle administration in the synovial space, i.e., a fast rate process causing a burst effect and involving the 59.5% of the total CP absorbed amount and a slow rate process, involving 40.5%. Interestingly, the CP burst effect inside the joint space enhances its diffusion towards cartilage resulting in CP accumulation in about three times higher concentrations than in plasma. In line with these results, the normalized-by-dose area under the concentration vs. time curve (AUC) values after IA were 80% lower than those observed after the intravenous. Moreover, the slower slope of the concentration–time terminal phase after IA administration vs. intravenous (IV) suggested a flip-flop phenomenon (0.35 h-1 vs. 0.19 h-1). Notably, CP clearances are predictive of the pharmacokinetic (PK) profile of CP in healthy humans (0.14 L/h/5 kg vs. 2.92 L/h/70 kg) although an over-estimation has been detected for cats or dogs (10 times and 4 times, respectively). This fact could probably be attributed to inter-species metabolic differences. In summary, despite the limited number of animals used, this study shows that the rabbit model could be suitable for a predictive evaluation of the release enhancement of CP-NP towards the biophase in arthritic diseases not due to sterical retention of the formulation.

Stationarity of spot freight rates considering supply/demand effect

The mean-reverting nature of freight rates is one of the important subjects in maritime economics. The classic understanding of maritime economics (and that of the shipping industry) suggests that freight rate processes are mean-reverting and approach the level decided by the demand/supply ratio. However, statistical tests on freight rate processes often reveal these processes to be non-stationary, which means the processes would not have a mean-reverting nature. In this study, we investigated the mean-reverting nature of Panamax freight rates (Baltic Panamax 4 T/C Average) for two “means”: the actual freight rate process itself, and the deviation process of actual freight rates from estimated ones based on the demand/supply ratio. The AR (1) model can be applied to both processes, and their autoregressive coefficient φ was between 0 and 1. In the actual freight process, φ was close to 1, and a unit root test failed to reject that the process is non-stationary. By contrast, in the deviation process, φ was sufficiently smaller than 1, and a unit root test rejected that the process is non-stationary. The result can resolve the contradiction between two views on mean-reverting nature; if we focus on the actual freight rate process itself and do not consider demand/supply, the process is non-stationary and does not have a mean-reverting nature. If we focus on the deviation process of the actual freight rates from the level decided by the demand/supply ratio, the process is stationary and tends to approach zero.