Genetic Aberrations of DNA Repair Pathways in Prostate Cancer: Translation to the Clinic

Prostate cancer (PC) is the second most common cancer in men worldwide. Due to the large-scale sequencing efforts, there is currently a better understanding of the genomic landscape of PC. The identification of defects in DNA repair genes has led to clinical studies that provide a strong rationale for developing poly (ADP-ribose) polymerase (PARP) inhibitors and DNA-damaging agents in this molecularly defined subset of patients. The identification of molecularly defined subgroups of patients has also other clinical implications; for example, we now know that carriers of breast cancer 2 (BRCA2) pathogenic sequence variants (PSVs) have increased levels of serum prostate specific antigen (PSA) at diagnosis, increased proportion of high Gleason tumors, elevated rates of nodal and distant metastases, and high recurrence rate; BRCA2 PSVs confer lower overall survival (OS). Distinct tumor PSV, methylation, and expression patterns have been identified in BRCA2 compared with non-BRCA2 mutant prostate tumors. Several DNA damage response and repair (DDR)-targeting agents are currently being evaluated either as single agents or in combination in patients with PC. In this review article, we highlight the biology and clinical implications of deleterious inherited or acquired DNA repair pathway aberrations in PC and offer an overview of new agents being developed for the treatment of PC.     

A New Method for Clearing Dyed Polyester Fabrics by Gemini Cationic Surfactants

In the study, a new treatment with cationic surfactants was proposed to remove deposited disperse dyes from polyester fabrics as an alternative to the traditional reduction clearing process. For this purpose, dodecyltrimethyl ammonium bromide and two gemini cationic surfactants (12-4-12 and 14-4-14) were investigated and the optimum operating conditions were obtained using a central composite design. Findings indicated that gemini cationic surfactants can be considered as the best candidates to remove deposited disperse dyes from polyester fabrics. This was confirmed by the results of the scanning electron microscope images, fastness properties and spectrophotometry.     

Dual layer stacked rectangular microstrip patch antenna for ultra wideband applications

An antenna consisting of a U-slotted rectangular microstrip patch stacked with another patch of a different size on a separate layer is presented and its performance results are investigated. An equivalent circuit model of this stacked patch design structure is also presented based on an extended cavity model to predict the input impedance. The theoretical input impedance is evaluated from this circuit model and the experimental results support the validity of the model. In this case, stacking with a simple patch adds another resonance to the antenna thus providing a wider bandwidth. The dimension of the top patch is optimised to achieve ultra wide bandwidth. A maximum impedance bandwidth of 56.8% is achieved using this structure, and the return loss |S₁₁|of the antenna is less than -10 dB between 3.06 and 5.49 GHz and the radiation patterns are found to be relatively constant throughout the band. A coaxial feed with Gaussian modulated pulse is used for this antenna.     

Cell neighbor list method for planar elongational flow: rheology of a diatomic fluid

We present simple changes to the cell method for neighbor list construction that enable it to be used in molecular dynamics studies of systems subject to a planar elongational flow field. The modifications for planar elongational flow are similar to those required for planar shear flow and should be easy to incorporate into any cell neighbor list method that is used in simulations of homogeneous shear. The execution time of the code at equilibrium is shown to be proportional to the number of particles N. The introduction of the modifications allowing shear, and more importantly, elongational flow are shown to affect the performance of the code in both CPU time and memory usage. The modifications to enable the simulation of planar elongational flow using the cell method of neighbor list construction will not introduce any higher order dependency if applied to code that is N-dependent in planar shear flow. We use this code to study large systems of diatomic molecules at low strain-rates, and find that the linear regime in planar elongational flow can be determined by the ratio of the two planar elongational viscosity functions. The properties investigated in planar shear flow, such as angular velocity and alignment angle, were inconsistent with the shear viscosity results in their evaluation of where the linear regime ends. The high precision of the results allowed us to accurately determine the coefficients in the retarded-motion expansion.     

Thermal buckling behavior of two-dimensional imperfect functionally graded microscale-tapered porous beam

This article presents a study on the thermal buckling behavior of two-dimensional functionally graded microbeams made of porous materials. The material composition varies along thickness and length of the microbeam based on the power law distribution. The microbeam is modeled within the framework of Euler–Bernoulli beam theory. The microbeam is considered having variable material composition along thickness. The equations are derived using the modified couple stress theory and the solving process is based on the generalized differential quadrature method. The validity of the results is shown through comparison of the results with the results of other published research.     

Achieving global environmental benefits through local development of clean energy? The case of small hilly hydel in India

Energy and development are closely intertwined. Yet, increasing fossil fuel-based energy consumption contributes significantly to environmental problems both locally and globally. This article explores the interlinkages between local livelihood and environmental benefits from the provision of energy to remote rural households through small hydropower development. The analysis is based on research carried out around a large development project designed to assist the Government of India in the optimum utilization of small hydropower resources in the Himalayan and sub-Himalayan regions. There are about 100,000 villages in India that are not connected to electricity supply, many of them in the hilly regions with ample hydropower potential. The project aimed to demonstrate the utility of and options for providing electricity to such villages through clean mini-hydro. The article addresses the nature of the impacts of the demonstration small hydel schemes on the local communities, to what extent they translate into environmental benefits both locally and globally, and the perceptions and participation of the local communities in these small hydro schemes. The study explores the impacts of the schemes on financial capital, natural capital, social capital, physical capital, human capital, and gender equity in the local communities. It further provides a discussion on the links between local and global environmental benefits. Overall, it is found that the schemes’ impacts both on the local communities and the environment are mostly marginally positive or neutral, although achieving clearly demonstrable benefits would require major upscaling of the effort involving broader changes than possible under this project. Furthermore, it is argued that some of the assumptions behind the project design were faulty. Involvement of the local communities and direct livelihood benefits to them are essential for the long-term sustainability of the small hydro schemes. The discussion and conclusions are intended to provide guidance to programmes and projects that aim to promote environmentally sound energy in the rural areas of developing countries.