Chemotherapy response and the role of the WWOX tumour suppressor

A thesis submitted to the University of Bedfordshire in fulfilment of the requirement of the degree of Doctor of PhilosophyPaclitaxel is a widely used chemotherapy drug for the treatment of multiple cancers. Paclitaxel works by inhibiting the disassembly of microtubules. Besides the role of paclitaxel in mitotic arrest, many studies suggest that paclitaxel could initiate apoptosis by activating ER-stress pathways. Cisplatin, another chemotherapy drug is also used for the treatment of solid tumours. It works by forming adducts with the structure of DNA leading to cell cycle arrest, DNA damage and apoptosis. These two chemotherapy drugs have different mechanisms of killing tumour cells, but they are often combined to give greater effect. WWOX is a tumour suppressor in many cancers. It has been shown that WWOX promotes apoptosis and suppresses in vivo tumorigenesis, but its function remains unclear. Here in my study I hypothesize that ER-stress is an important part of paclitaxel response in cancer cells, and the WWOX tumour suppressor is important in mediating paclitaxel induced ER-stress response. I also hypothesize that WWOX is important in mediating the apoptotic response to cisplatin. My results show that paclitaxel could not induce ER stress in multiple cancer cells lines, and WWOX did not affect the cytotoxic action of paclitaxel. I show some evidence that ER-stress may influence survival in ovarian cancer patients, but this is independent of the effect of WWOX expression. I show that WWOX is not important for cisplatin response since cisplatin suppresses the expression of WWOX. This effect may relate to its location at a common fragile site since cisplatin also down-regulates another fragile site-associated gene FHIT. However, I also show the apparent involvement of NF-kB2 and PAR2 transcription factors in the down regulation of WWOX. These findings increase our understanding of the unintended effects of chemotherapy treatments

The Federalisation of Cooperative Banking in Pakistan and Rural Cooperatives in Punjab Province

The creation of Pakistan on 14 August 1947 was the result of the irresistible and massive pressure of Muslim nationalism. The British colonial government, despite its initial reservations on the practicability and soundness of the demand, came around to the viewpoint of the Muslims and agreed to partition India. The Pakistan that came into being had two geographical units separated by 1,600 miles of Indian territory. The Eastern Wing became the independent Republic of Bangladesh at the end of 1971. Pakistan now comprises the West Wing of the Pakistan created in 1947

Organizational Resilience: A Dynamic Capability of Complex Systems

In recent years, the concept of organizational resilience has largely attracted the interest of academicians and practitioners alike. A fair number of researches have been conducted on developing the concept of organizational resilience. However, there seems to be a lack of consensus over its conceptualization mainly because the concept itself is prodigious and is used in a variety of disciplines. Furthermore, research within the domain of organizational resilience has been outcome oriented; however, questions addressing the drivers of resilience are yet to be answered. On the other hand, research within the domain of dynamic capabilities view have long been criticized as tautological, resistant to operationalization, and lacking the unification of thought. However, there exists a sufficient degree of conceptual similitude between the two concepts, mainly due to their epistemological similarities grounded within the theoretical assumptions of chaotic systems, environmental dynamism, and systems thinking. Incorporating both perspectives in parallel for understanding the theoretical connections can lead to clarifications at an ontological level. Therefore, this paper attempts to propose a holistic model of organizational resilience by incorporating a lens metaphor of dynamic capabilities view. This paper is divided into four sections. The first section of this paper lays down the multidisciplinary discourses within the realm of organizational resilience. The second section highlights the management discourse about the conceptualization of organizational resilience. The third section of this paper uses a lens metaphor of dynamic capabilities view in an attempt to add depth to the concept of organizational resilience. The fourth and the final section attempts to propose the drivers of organizational resilience from a strategic viewpoint

Case series of rare Interstitial Lung Disease (ILD).

Pulmonary alveolar proteinosis (PAP) is a rare lung disease where periodic acid Schiff (PAS)-positive eosinophilic material accumulates in the alveoli of the lungs. Here we describe two cases of young males who presented with dynpnoea and weight loss. The HRCT scan of the chest in both cases showed the typical crazy-paving pattern and lung biopsies confirmed the diagnosis of PAP. They showed remarkable symptomatic improvement with therapeutic whole lung lavage

Relative efficacy of organic substrates on maize root proliferation under water stress

The aggravating threat for today's agriculture is provision of food security to ever-escalating population utilizing scarce resources. Water scarcity is restraining humans to produce more from drops of water in place of gallons. Root is present at soil-plant interface and is main water extractor for plant. Its growth pattern varies as soil moisture conditions fluctuates. Present pot study consisting of two factors i.e. organic substrates (Farm manure, Poultry Manure and Molasses) and different water stress levels {50, 75, 100 and 125% of available water contents (AWCs)} using maize as test crop to assess their impact on different growth parameters (especially root growth). The experiment was conducted using completely randomized design CRD under factorial arrangement. Root length (44.5 cm), root fresh & dry biomass (71.1 g and 24.3 g, respectively), root diameter (1.73 mm), root volume (0.24 cm3) and root length density (7.4 x 10-3 cm cm-3) were observed in farm manure treated pots at 75% AWC that was statistically indistinguishable from all other treatments at same water level and 100% water availability but eloquently greater than plants of all treatments at 50% and 125% available water contents. Shoot length, dry and fresh weights were observed greater in plants having 100% available moistures. They were statistically at par with 75% water treated plants. Comparing treatments for all the parameters in multivariate cluster analysis it was concluded that 75% available water contents produce almost similar to 100% along with the benefit of water security

Comparative analysis of AC and DC distribution system with respect to harmonic distortion considering daily load profile

Electrical energy is the most efficient and the cleanest form of energy at the moment that is being transmitted and distributed amongst end-users. From its earlier days, the AC system was preferred as an economical solution for transmission and distribution. However, the development in the power electronics technology and the evolution of highly efficient power electronic converters have established the resurgence of DC power system. Furthermore, the trend is shifting towards DC loads as various energy efficient appliances, such as DC inverter air conditioners, operate on DC nowadays. This further advocates the shift towards the DC power system. This research works is an effort to perform the comparative analysis of AC Distribution System (ACDS) and DC Distribution System (DCDS), with regards to power quality and harmonic distortion in particular. The comparison is performed considering load profile and load variation on daily basis. Simulations are performed in MATLAB. It has been concluded at the end that ACDS is better than DCDS in terms of power quality as total harmonic distortion of the DCDS under the same loading and same load variation during the whole day was significantly higher than that of ACDS

PID VS PI CONTROL OF SPEED GOVERNOR FOR SYNCHRONOUS GENERATOR BASED GRID CONNECTED MICRO HYDRO POWER PLANT

Most of the micro hydro power plants operating in isolated mode are based upon induction generator technology. However; in the recent years, there has been a growing interest in the use of synchronous generator based Micro Hydro Power Plants (MHPPs), for grid connected systems, because of the proven advantages over other renewable technologies where the extension of grid systems are economically viable for grid connection. Among various other components of micro hydro power plants, the speed governor mainly functions to control the hydraulic turbine. It constitutes not only the control mechanism but also the actuating equipment to regulate the flow of water, to start and stop the unit, and to regulate the speed and power output of the generator in case of any electrical disturbance. The proper control of actuating devices for these governors plays a significant role in stable and acceptable operation of the connected power system. The use of the Proportional-Integral-Derivative (PID) based control in speed governors is now gaining popularity because of the simplicity and flexibility. This research work makes an effort to analyze the behavior of the PID vs PI (Proportional-Integral) controllers; for speed governor operation of grid connected MHPP, deploying synchronous generator, under the influence of a electrical disturbance; to identify  more suitable controller from the regulation point of view. The dynamic performance of the proposed controllers for speed governor function is fully validated through digital simulations carried out using MATLAB/Simulink software package

ANALYZING THE IMPACT OF HVDC TRANSMISSION ON A DISTRIBUTION SYSTEM LOADED WITH NON LINEAR LOADS

Owing to several economic and technical benefits over AC transmission, High Voltage Direct Current Transmission (HVDC) has drawn a lot of attention in recent times. HVDC gives rise to harmonic distortion due to the power flow through power electronic inverters. The scenario gets even more critical by considering the increased influx of non linear loads in distribution systems. This research work strives to evaluate the impact of HVDC inverters on such distribution systems. The harmonic model of the inverter, developed by experimentation, is modified to decrease the harmonic distortion; which is then used for simulating a generic UK residential distribution system deploying Electrical Transient Analyzer Program. The simulation results indicate increased harmonic distortion in voltage beyond standard limits at high tension as well as low tension sides of the distribution transformer. The results also show that harmonic distortion produced by the HVDC inverters may trigger resonance at a particular harmonic frequency

Unraveling the Influence of Land-Use Change on δ 13C, δ 15N, and Soil Nutritional Status in Coniferous, Broadleaved, and Mixed Forests in Southern China: A Field Investigation

Natural isotopic abundance in soil and foliar can provide integrated information related to the long-term alterations of carbon (C) and nitrogen (N) cycles in forest ecosystems. We evaluated total carbon (TC), total nitrogen (TN), and isotopic natural abundance of C (δ 13C) and N (δ 15N) in soil and foliar of coniferous plantation (CPF), natural broadleaved forest (NBF), and mixed forest stands at three different soil depths (i.e., 0–10, 10–20, and 20–40 cm). This study also explored how soil available nutrients are affected by different forest types. Lutou forest research station, located in Hunan Province, central China, was used as the study area. Results demonstrated that the topsoil layer had higher TC and TN content in the mixed forest stand, resulting in a better quality of organic materials in the topsoil layer in the mixed forest than NBF and CPF. In general, soil TC, TN, and δ 15N varied significantly in different soil depths and forest types. However, the forest type did not exhibit any significant effect on δ 13C. Overall, soil δ 13C was significantly enriched in CPF, and δ 15N values were enriched in mixed forest. Foliar C content varied significantly among forest types, whereas foliar N content was not significantly different. No big differences were observed for foliar δ 15N and δ 13C across forest types. However, foliar δ 13C and δ 15N were positively related to soil δ 13C and δ 15N, respectively. Foliar N, soil and foliar C:N ratio, soil moisture content (SMC), and forest type were observed as the major influential factors affecting isotopic natural abundance, whereas soil pH was not significantly correlated. In addition, forest type change and soil depth increment had a significant effect on soil nutrient availability. In general, soil nutrient availability was higher in mixed forest. Our findings implied that forest type and soil depth alter TC, TN, and soil δ 15N, whereas δ 13C was only driven by soil depth. Moreover, plantations led to a decline in soil available nutrient content compared with NBF and mixed forest stand

Intercropping of peanut–tea enhances soil enzymatic activity and soil nutrient status at different soil profiles in Subtropical Southern China

Intercropping is one of the most widely used agroforestry techniques, reducing the harmfulimpacts of external inputs such as fertilizers. It also controls soil erosion, increases soil nutrientsavailability, and reduces weed growth. In this study, the intercropping of peanut (ArachishypogaeaL.)was done with tea plants (Camellia oleifera), and it was compared with the mono-cropping of tea andpeanut. Soil health and fertility were examined by analyzing the variability in soil enzymatic activityand soil nutrients availability at different soil depths (0–10 cm, 10–20 cm, 20–30 cm, and 30–40 cm).Results showed that the peanut–tea intercropping considerably impacted the soil organic carbon(SOC), soil nutrient availability, and soil enzymatic responses at different soil depths. The activityof protease, sucrase, and acid phosphatase was higher in intercropping, while the activity of ureaseand catalase was higher in peanut monoculture. In intercropping, total phosphorus (TP) was 14.2%,34.2%, 77.7%, 61.9%; total potassium (TK) was 13.4%, 20%, 27.4%, 20%; available phosphorus (AP)was 52.9%, 26.56%, 61.1%; 146.15% and available potassium (AK) was 11.1%, 43.06%, 46.79% higherthan the mono-cropping of tea in respective soil layers. Additionally, available nitrogen (AN) was51.78%, 5.92%, and 15.32% lower in the 10–20 cm, 20–30 cm, and 30–40 cm layers of the intercroppingsystem than in the mono-cropping system of peanut. Moreover, the soil enzymatic activity wassignificantly correlated with SOC and total nitrogen (TN) content across all soil depths and croppingsystems. The depth and path analysis effect revealed that SOC directly affected sucrase, protease,urease, and catalase enzymes in an intercropping system. It was concluded that an increase in the soilenzymatic activity in the intercropping pattern improved the reaction rate at which organic matterdecomposed and released nutrients into the soil environment. Enzyme activity in the decompositionprocess plays a vital role in forest soil morphology and function. For efficient land use in the croppingsystem, it is necessary to develop coherent agroforestry practices. The results in this study revealedthat intercropping certainly enhance soil nutrients status and positively impacts soil conservation.The funding sources include the National Science and Technology Support Grant ofChina (2015BAD07B0503), Forestry Science and Technology Promotion Project of China (No. 122017) and Postdoctoral research funding of Central South University of Forestry and Technology(70702-45200003)