Formulation and evaluation of transdermal drug-delivery system of isosorbide dinitrate

The purpose of this study was to develop a reservoir-type transdermal delivery system for isosorbide dinitrate (ISDN). The developed patch consisted of five layers from bottom to top, namely, a temporary liner, an adhesive layer, a rate-controlling membrane, a reservoir and a backing. The effects of chemical penetration enhancers, reservoir materials and rate-controlling membranes on the release behaviour of ISDN from the transdermal patch were studied, and the; in vitro; release of ISDN from the developed patch was studied and compared with the commercially available ISDN patch. The results showed that there was no significant difference in permeation rates between the developed reservoir-type patch and the commercially available ISDN patch (;p;>; 0.05). Moreover, the cumulative release ratio of the commercially available ISDN patch in 48 h was up to 89.8%, whereas the developed patch was only 34.9%, which meant the sustained release time of the developed patch was much longer than the commercially available ISDN patch, and would promote the satisfaction of the patient.;O objetivo do presente estudo foi desenvolver um sistema de liberação transdérmico do tipo reservatório para o dinitrato de isossorbida (ISDN, abrevitura em Inglês). A formulação transdérmica desenvolvida constou de cinco camadas de baixo para cima, ou seja, um revestimento temporário, uma camada adesiva, uma membrana controladora da taxa de liberação, um reservatório e um reforço. Estudaram-se os efeitos dos potenciadores de penetração química, materiais do reservatório e membranas de controle da taxa de liberação no comportamento da formulação transdérmica de dinitrato de isossorbida. A liberação; in vitro; da formulação transdérmica de dinitrato de isossorbida desenvolvida foi estudada em comparação com a formulação de dinitrato de isossorbida disponível comercialmente. Os resultados mostraram que não existem diferenças significativa nas taxas de permeação entre o tipo de reservatório desenvolvido e o de dinitrato de isossorbida desenvolvido comercialmente (;p;>;0,05). Ademais, a taxa de liberação cumulativa da formulação de dinitrato de isossorbida disponível comercialmente em 48 horas foi de até 89,8% e a da formulação desenvolvida, de apenas de 34,9%, o que provou que a liberação sustentada da formulação desenvolvida foi muito maior do que a de dinitrato de isossorbida desenvolvida comercialmente, o que promoveria a satisfação do paciente.

Integrated Behavior Planning and Motion Control for Autonomous Vehicles with Traffic Rules Compliance

In this article, we propose an optimization-based integrated behavior planning and motion control scheme, which is an interpretable and adaptable urban autonomous driving solution that complies with complex traffic rules while ensuring driving safety. Inherently, to ensure compliance with traffic rules, an innovative design of potential functions (PFs) is presented to characterize various traffic rules related to traffic lights, traversable and non-traversable traffic line markings, etc. These PFs are further incorporated as part of the model predictive control (MPC) formulation. In this sense, high-level behavior planning is attained implicitly along with motion control as an integrated architecture, facilitating flexible maneuvers with safety guarantees. Due to the well-designed objective function of the MPC scheme, our integrated behavior planning and motion control scheme is competent for various urban driving scenarios and able to generate versatile behaviors, such as overtaking with adaptive cruise control, turning in the intersection, and merging in and out of the roundabout. As demonstrated from a series of simulations with challenging scenarios in CARLA, it is noteworthy that the proposed framework admits real-time performance and high generalizability.Comment: 7 pages, 5 figures, accepted for publication in The 2023 IEEE International Conference on Robotics and Biomimetics (ROBIO

Detecting Change-Points in Epidemic Models

Abstract. The purpose of this research is to propose a new method for detecting change points with an epidemic alternative (in the form of a step function). There are several parametric approaches and nonparametric approaches in the literature that can be used for detecting change-points in epidemic models. Yan [16] summarized some existing parametric approaches. The approaches summarized in Yao's paper are based on the assumption of known population variances. The proposed test statistic in this research does not depend on the assumption of known population variances. This better fits the real world situation. Monte-Carlo simulation was used to find the critical values of the test. The power study was also based on Monte-Carlo simulation. The simulation result shows that the test statistic proposed in this research provides quite decent power compared with other existing statistical procedures, especially for the case that the step is large and duration of the epidemic is long. In 1997, a likelihood ratio test was proposed by Csorgo and Horvath Keywords: Change-point, epidemic alternative, power comparison, Monte Carlo simulation, unknown variances. Introduction The problem of detecting changes in the characteristics of a random process is referred to as the changepoint problem. This problem has become a fast developing research area in statistics mainly due to its important applications and newly developed theoretical and computational methods. Change-point problems occur in a wide variety of fields including detecting shifts in production processes, comparing and matching DNA sequences, examining the impact of social programs, and studying structural shifts in one or more parameters of the models in economics, engineering, political science and other empirical sciences. Change-points with epidemic alternatives were formulated by Levin and Kline [11] to model the changes over time in the proportion of abortions. In the epidemic change model, the random process is assumed to be stable initially, and then at an unknown time point it will exhibit an abrupt change in the characteristics, which will continue for an unknown duration before stabilizing again to the initial state. The standard normal of a neuron exhibiting a modulated activity during a time period and then reverting to its spontaneous activity is an example of this model, which was described by Commenges, et al [12]. Bromeling and Tsurumi [13] described a number of applications of this model in econometrics. Later, Siegmun

Population genetic structure of the deep‐sea mussel Bathymodiolus platifrons (Bivalvia: Mytilidae) in the Northwest Pacific

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Evolutionary Applications 11 (2018): 1915-1930, doi:10.1111/eva.12696.Studying population genetics of deep‐sea animals helps us understand their history of habitat colonization and population divergence. Here, we report a population genetic study of the deep‐sea mussel Bathymodiolus platifrons (Bivalvia: Mytilidae) widely distributed in chemosynthesis‐based ecosystems in the Northwest Pacific. Three mitochondrial genes (i.e., atp6, cox1, and nad4) and 6,398 genomewide single nucleotide polymorphisms (SNPs) were obtained from 110 individuals from four hydrothermal vents and two methane seeps. When using the three mitochondrial genes, nearly no genetic differentiation was detected for B. platifrons in the Northwest Pacific. Nevertheless, when using SNP datasets, all individuals in the South China Sea (SCS) and three individuals in Sagami Bay (SB) together formed one genetic cluster that was distinct from the remaining individuals. Such genetic divergence indicated a genetic barrier to gene flow between the SCS and the open Northwest Pacific, resulting in the co‐occurrence of two cryptic semi‐isolated lineages. When using 125 outlier SNPs identified focusing on individuals in the Okinawa Trough (OT) and SB, a minor genetic subdivision was detected between individuals in the southern OT (S‐OT) and those in the middle OT (M‐OT) and SB. This result indicated that, although under the influence of the Kuroshio Current and the North Pacific Intermediate Water, subtle geographic barriers may exist between the S‐OT and the M‐OT. Introgression analyses based on these outlier SNPs revealed that Hatoma Knoll in the S‐OT represents a possible contact zone for individuals in the OT‐SB region. Furthermore, migration dynamic analyses uncovered stronger gene flow from Dai‐yon Yonaguni Knoll in the S‐OT to the other local populations, compared to the reverse directions. Taken together, the present study offered novel perspectives on the genetic connectivity of B. platifrons mussels, revealing the potential interaction of ocean currents and geographic barriers with adaption and reproductive isolation in shaping their migration patterns and genetic differentiation in the Northwest Pacific.General Research Fund Grant Number: HKBU12302917; Hong Kong Baptist University Grant Number: 15‐1012‐P0

Optimization of Ganoderma leucocontextum Fermented Tea Medium Formula Based on High-yield Extracellular Crude

To investigate the optimal nutritional conditions and their contributing factors for the secretion of extracellular crude polysaccharides with Ganoderma leucocontextum on a liquid tea substrate, this study optimized the nutritional conditions of its extracellular crude polysaccharides formation by orthogonal experiment and analysis of variance on the basis of the single-factor test, and explored the relevance between its liquid culture characteristics and the secretion of extracellular crude polysaccharides using correlation and path analyses. The results of study revealed that the greatest output of extracellular crude polysaccharide (1.49±0.33 g/L) was achieved on a tea culture medium of 50 g/L potato, 40 g/L glucose, 3 g/L laterite, 20 g/L Pu'er tea and 0.075 mm tea powder particle size, and was affected by each nutritional condition in the descending order of glucose>tea variety>laterite>potato>tea powder particle size. Moreover, the secretion of extracellular crude polysaccharides in G. leucocontextum was significantly impacted by the soluble solids of the fermentation broth and the number of mycelium balls, with the former having the greatest indirect effect while the latter, the greatest direct and combined effect on it. In conclusion, the nutritional conditions (variety, concentration, particle size, etc.) of the tea culture medium and the liquid culture characteristics of G. leucocontextum exerted a significant and interactive effect on the secretion of extracellular crude polysaccharides, and the aforesaid results may provide a theoretical reference for extraction of polysaccharides from this mushroom and development of it as functional foods

Intensive Glucose Control Reduces the Risk Effect of TRIB3, SMARCD3, and ATF6 Genetic Variation on Diabetic Vascular Complications

Type 2 diabetes mellitus is a complex disease. Our previous study revealed that TRIB3 genetic variations were strongly associated with diabetic vascular complications, although TRIB3 regulation pathways remain poorly understood. We used two extreme treatment groups from a 2 × 2 factorial randomized controlled trial to identify a positive association, which was further validated in patients receiving cross treatment to test the effect of genetic polymorphisms among the different treatment groups. A gene-centric score (GS)-weighted model including the three associated genetic variations TRIB3 rs2295490, ATF6 rs12086247, and SMARCD3 rs58125572 was used. The results of the GS model indicated a 46% reduction in the risk of primary vascular complications in patients bearing more than two risk alleles [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.38–0.76, p < 0.001], following intensive glucose control treatment when compared with patients who received standard glucose control treatment. Furthermore, these patients benefited from active blood pressure-lowering treatment (HR 0.39, 95% CI 0.24–0.64, p < 0.001). However, no significant difference was observed between the two interventions in patients with fewer than two risk alleles (HR 1.09, 95% CI 0.86–1.39, p = 0.47). These results indicate that genetic variants in these three genes may be useful biomarkers for individualized drug therapy in diabetic patients

Towards understanding Android system vulnerabilities: Techniques and insights

National Research Foundation (NRF) Singapor