Pavement Quality Index Rating Strategy Using Fracture Energy Analysis for Implementing Smart Road Infrastructure.

Developing a responsive pavement-management infrastructure system is of paramount importance, accentuated by the quest for sustainability through adoption of the Road Traffic Management System. Technological advances have been witnessed in developed countries concerning the development of smart, sustainable transportation infrastructure. However, the same cannot be said of developing countries. In this study, the development of a pavement management system at network level was examined to contribute towards a framework for evaluating a Pavement Quality Index and service life capacity. Environmental surface response models in the form of temperature and moisture variations within the pavement were applied, using sensor devices connected to a data cloud system to carry out mathematical analysis using a distinctive mesh analysis deformation model. The results indicated variation in the Resilient Modulus of the pavement, with increasing moisture content. Increase in moisture propagation increased saturation of the unbound granular base which reduced the elastic modulus of the sub-base and base layer and reduced the strength of the pavement, resulting in bottom-up cracks and cracking failure. The horizontal deformation reduced, indicating that the material was experiencing work hardening and further stress would not result in significant damage. Increasing temperature gradient resulted in reduced stiffness of the asphalt layer. In tropical regions, this can result in rutting failure which, over time, results in top-down cracks and potholes, coupled with increasing moisture content.

Corporate capital structure effects on corporate performance pursuing a strategy of innovation in manufacturing companies.

Within the sphere of finance, the concept of capital structure has long been a subject of intense debate, serving as a quantitative depiction of the balance between debt, preference shares, and common stock within a company. This structure serves a crucial role in optimizing the utilization of a company's existing resources while simultaneously elevating the revenue streams for stakeholders. This particular study delves into the intricate relationship between corporate performance and capital structure, focusing on 78 publicly listed firms within the Dhaka Stock Exchange (DSE). Bangladesh holds the 29th position globally in terms of purchasing power, lending significant weight to this investigation. To comprehensively analyze this correlation, panel data encompassing the span from 2017 to 2021 was collected for these 78 sample companies operating within the DSE. Several key determinants of capital structure were considered in this analysis, namely the debt-to-equity ratio, short-term leverage ratio, long-term leverage ratio, and total debt ratio. Meanwhile, the performance of these firms was gauged using key metrics such as Return on Assets (ROA), Return on Equity (ROE), and Earnings Per Share (EPS). To ensure a robust analysis, factors such as inflation, liquidity, growth rate, tax rate, and firm size were meticulously controlled for. The findings unveiled a compelling narrative: all forms of debt ratios-be it short-term, long-term, or the total debt ratio-exhibited a substantial negative impact on ROA at a significant level of 1 %. Conversely, specific debt ratios, like the short-term total debt and the total debt-to-total asset ratio, displayed a notable positive correlation with ROE at a 1 % significance level. Intriguingly, the long-term total debt ratio yielded a negative and insignificant effect on ROE. Moreover, within the spectrum of predictors influencing a firm's performance, the liquidity ratio emerged as a non-significant factor-a notable discovery that highlights the nuanced nature of the interplay between capital structure and performance within these companies.

Dynamics and Structure Formation of Confined Polymer Thin Films Supported on Solid Substrates.

The stability/instability behavior of polystyrene (PS) films with tunable thickness ranging from higher as-cast to lower residual made on Si substrates with and without native oxide layer was studied in this paper. For further extraction of residual PS thin film (hresi) and to investigate the polymer-substrate interaction, Guiselin's method was used by decomposing the polymer thin films in different solvents. The solvents for removing loosely adsorbed chains and extracting the strongly adsorbed irreversible chains were selected based on their relative desorption energy difference with polymer. The PS thin films rinsed in chloroform with higher polarity than that of toluene showed a higher decrease in the residual film thickness but exhibited earlier growth of holes and dewetting in the film. The un-annealed samples with a higher oxide film thickness showed a higher decrease in the PS residual film thickness. The effective viscosity of PS thin films spin-coated on H-Si substrates increased because of more resistance to flow dynamics due to the stronger polymer-substrate interaction as compared to that of Si-SiOx substrates. By decreasing the film thickness, the overall effective mobility of the film increased and led to the decrease in the effective viscosity, with matching results of the film morphology from atomic force microscopy (AFM). The polymer film maintained low viscosity until a certain period of time, whereupon further annealing occurred, and the formation of holes in the film grew, which ultimately dewetted the film. The residual film decrement, growth of holes in the film, and dewetting of the polymer-confined thin film showed dependence on the effective viscosity, the strength of solvent used, and various involved interactions on the surface of substrates.

Interruption of nuclear factor kappaB signaling by the androgen receptor facilitates 12-O-tetradecanoylphorbolacetate-induced apoptosis in androgen-sensitive prostate cancer LNCaP cells.

12-O-tetradecanoylphorbolacetate (TPA) influences proliferation, differentiation, and apoptosis in a variety of cells including prostate cancer cells. Here, we show that androgen treatment potentiates TPA-induced apoptosis in androgen-sensitive prostate cancer LNCaP cells but not in androgen-independent prostate cancer cell lines DU145 and PC-3. The use of the antiandrogen bicalutamide (Casodex) rescued LNCaP cells from 5-alpha-dihydrotestosterone (DHT)/TPA-induced apoptosis, suggesting that DHT/TPA-induced apoptosis is mediated by androgen/androgen receptor (AR). In addition, a caspase-3 inhibitor (Ac-DEVD-CHO) reduced the level of apoptosis, suggesting that DHT/TPA-mediated apoptosis occurs through a caspase-3-dependent pathway. A functional reporter assay using nuclear factor (NF) kappaB-luciferase and an electromobility gel shift assay showed that DHT suppressed NFkappaB activity. In addition, apoptosis mediated by combined DHT/TPA treatment was abrogated by overexpression of the NFkappaB subunit p65 in LNCaP-p65 cells, suggesting that NFkappaB may play an important role in regulating the effects of androgen/AR and TPA on apoptosis. Furthermore, use of the c-Jun N-terminal kinase (JNK) inhibitor SB202190 showed that the combination of DHT/TPA increased JNK activation in LNCaP cells but not in LNCaP-p65 cells, demonstrating that NFkappaB may be able to suppress JNK activity. These results indicate that androgen/AR facilitates TPA-induced apoptosis by interruption of the NFkappaB signaling pathway, leading to activation of JNK in LNCaP cells. These data describe a signaling pathway that could potentially be useful in proposed therapeutic treatment strategies exploiting combinations of different agents that control apoptosis in prostate tumors.

Molecular basis for the antiandrogen withdrawal syndrome.

In patients with prostate cancer who manifest disease progression during combined androgen blockade therapy, discontinuation of antiandrogen treatment might result in prostate-specific antigen decline, often associated with clinical improvement. The response called antiandrogen withdrawal syndrome is thus acknowledged as a general phenomenon. However, molecular mechanisms responsible for this syndrome are not completely understood. This article outlines the proposed mechanisms, including alterations of androgen receptor gene and its coregulatory proteins and activation of the signal transduction pathway, and the potential therapeutic approaches based on the specific mechanisms.

Inactivation of androgen receptor coregulator ARA55 inhibits androgen receptor activity and agonist effect of antiandrogens in prostate cancer cells.

Antiandrogens given to antagonize androgen receptor (AR) activity gradually lose their efficacy as antagonists and eventually function as agonists to promote (instead of block) AR-mediated growth of prostate cancer cells. The mechanisms of how antiandrogens acquire this agonist activity during hormonal therapy are largely unknown. Here, we report that expression of a dominant-negative AR-associated protein 55 (dARA55) coregulator, inhibits AR transcriptional activity and reduces the agonist activity of antiandrogens. Inducibly expressed dARA55 inhibits prostate-specific antigen and cell growth in prostate cancer cells. Further dissection of the molecular mechanism shows dARA55 can selectively suppress endogenous AR-associated protein 55 (ARA55) enhanced AR transactivation by means of interruption of dimerization between ARA55 and ARA55. These results were confirmed by using RNA interference-mediated silencing of the ARA55 gene. These results therefore provide evidence that AR function could be suppressed without mutation or change in AR itself. Taken together, these findings not only demonstrate the important roles of the ARA55 coregulator in the AR-mediated growth of prostate cancer, they also may provide a critical target for developing therapeutic agents for the antiandrogen therapy that almost always fails in the treatment of hormone-refractory prostate cancer.

Reducing the agonist activity of antiandrogens by a dominant-negative androgen receptor coregulator ARA70 in prostate cancer cells.

Although the progression of prostate cancer initially is dependent on androgens, tumor progression to an androgen-independent growth eventually occurs in most of patients treated with androgen ablation and/or antiandrogen therapy. After the initial response, antiandrogens lose their efficacy and eventually act as agonists to promote androgen receptor (AR)-mediated growth of prostate cancer cells. An aberrant regulation of AR activity, presumably by AR coregulators, may contribute to this acquired agonist activity of antiandrogens. Using an in vitro mutagenesis and a double-negative selection in yeast two-hybrid screening, we have identified a dominant-negative AR coregulator ARA70 (dARA70N), which can inhibit AR transcriptional activity by inactivating the normal function of ARA70 in the LNCaP cells. Whereas ARA70 in oligomeric form interacts with AR and enhances its transcriptional activity, dARA70N lacks AR interaction and might retain the ability to form a non-functional heteromer with ARA70 and interrupt AR transcriptional activity without a change in AR protein itself. The addition of dARA70N reduces the agonist activity and rescues the normal function of antiandrogens in prostate cancer cells. RNA-interference-mediated silencing of ARA70 gene further confirms these observations. Taken together, these findings indicate that ARA70 may contribute to the acquired agonist activity of antiandrogens and plays an important role in making prostate cancer cells resistant to androgen ablation and/or antiandrogen therapy. ARA70 may, thus, be a critical target for developing therapeutic agents against AR-mediated progression of prostate cancer.

A dominant-negative mutant of androgen receptor coregulator ARA54 inhibits androgen receptor-mediated prostate cancer growth.

The ligand-bound androgen receptor (AR) regulates target genes via a mechanism involving coregulators such as androgen receptor-associated 54 (ARA54). We investigated whether the interruption of the AR coregulator function could lead to down-regulation of AR activity. Using in vitro mutagenesis and a yeast two-hybrid screening assay, we have isolated a mutant ARA54 (mt-ARA54) carrying a point mutation at amino acid 472 changing a glutamic acid to lysine, which acts as a dominant-negative inhibitor of AR transactivation. In transient transfection assays of prostate cancer cell lines, the mt-ARA54 suppressed endogenous mutated AR-mediated and exogenous wild-type AR-mediated transactivation in LNCaP and PC-3 cells, respectively. In DU145 cells, the mt-ARA54 suppressed exogenous ARA54 but not other coregulators, such as ARA55-enhanced or SRC-1-enhanced AR transactivation. In the LNCaP cells stably transfected with the plasmids encoding the mt-ARA54 under the doxycycline inducible system, the overexpression of the mt-ARA54 inhibited cell growth and endogenous expression of prostate-specific antigen. Mammalian two-hybrid assays further demonstrated that the mt-ARA54 can disrupt the interaction between wild-type ARA54 molecules, suggesting that ARA54 dimerization or oligomerization may play an essential role in the enhancement of AR transactivation. Together, our results demonstrate that a dominant-negative AR coregulator can suppress AR transactivation and cell proliferation in prostate cancer cells. Further studies may provide a new therapeutic approach for blocking AR-mediated prostate cancer growth.