Apoptosis and mitotic slippage following drug intervention in leukaemia cells

PhDThe response of leukaemia cells to therapeutic agents includes cell cycle arrest and apoptosis. The former response is useful in retarding disease progression, but induction of the latter is essential for disease eradication. Cell death is often related to toxicity so reducing drug-concentration or sensitising target cells to apoptosis is desirable. The relationship between the cell cycle and cell death has been at the centre of recent investigation focusing on mechanisms of cell death that are not driven directly by apoptotic responses. These mechanisms included mitotic catastrophe and mitotic slippage. The K562 myeloid leukaemia cell line exhibits a combination of p53 negativity and carries the Bcr-Abl t (9:22) Philadelphia chromosome. Bcr-Abl is a powerful anti-apoptotic translocation and is the hallmark of chronic myeloid leukaemia (CML). The absence of p53-mediated apoptosis and the anti-apoptotic effects of Bcr-abl delays drug-induced cell death, leaving a window of opportunity to investigate the effects of different agents on leukaemia cells. My investigations show that when DNA-targeting agents are used against myeloid leukaemia cells, G2 cell cycle arrest and apoptosis do not occur together i.e. cell cycle arrest precludes cell death; cells may escape G2 arrest as a result of mitotic slippage. In contrast, when anti-mitotic agents are used, it is necessary to induce mitotic arrest to subsequently induce apoptosis; thus lower concentrations are more effective in inducing apoptosis than higher drug concentrations. Evidence is provided suggesting reduced concentrations of both genotoxic agents and anti-mitotic agents may share a common pathway in inducing cell death that is related to events at mitosis and I suggest that this pathway has potential for exploitation by new agents currently in clinical trials, such as UCN-01, Purvanol, Roscovitine and agents that target the passenger proteins, in reducing the concentration of more conventional agents required to kill the Bcr-Abl positive leukaemias

Experimental investigation of a novel heat pipe and porous ceramic based indirect evaporative cooler

The paper presents laboratory test results of an integrated heat pipe and ceramic tube based evaporative cooling prototype for air conditioning in buildings. The cooler integrates durable porous ceramic tubes as water saturated media materials and heat pipes as efficient heat transfer devices. The ceramic tubes and the heat pipes straddle across two separate air ducts to form a wet and dry channel respectively. The thermal performance of the cooler was measured at various air inlet conditions of temperature, humidity and mass flow rates. The experimental measurements show that the cooling system can provide sufficient cooling as high as 1220 W/m2 of the wet media exposed surface area and depressing ambient temperature to 12℃. Equally, it was measured that the wet bulb effectiveness of the cooler can reach 86%

Experimental investigation of a novel heat pipe and porous ceramic based indirect evaporative cooler

The paper presents laboratory test results of an integrated heat pipe and ceramic tube based evaporative cooling prototype for air conditioning in buildings. The cooler integrates durable porous ceramic tubes as water saturated media materials and heat pipes as efficient heat transfer devices. The ceramic tubes and the heat pipes straddle across two separate air ducts to form a wet and dry channel respectively. The thermal performance of the cooler was measured at various air inlet conditions of temperature, humidity and mass flow rates. The experimental measurements show that the cooling system can provide sufficient cooling as high as 1220 W/m2 of the wet media exposed surface area and depressing ambient temperature to 12℃. Equally, it was measured that the wet bulb effectiveness of the cooler can reach 86%

Ascites: Causes, Diagnosis, and Treatment

Ascites is a pathological accumulation of fluid in the peritoneal cavity. Cirrhosis is the most common cause of ascites, representing for 85% of cases. More than one cause may be responsible for the development of ascites (multifactorial). Development of ascites is a poor prognostic event in the natural history of cirrhosis, with approximately 15 and 44% of patients with ascites succumbing in 1 and 5 years, respectively. Patients with cirrhosis need referral for liver transplantation after development of ascites. Proper history and physical examination are important in diagnosing the cause of ascites. Diagnostic paracentesis and abdominal sonogram should be performed during initial evaluation. Low salt diet and diuretic are the initial treatment option, and large volume paracentesis is an option for non‐responder to diuretics. Transjugular intrahepatic portosystemic stent‐shunt (TIPS) is highly valuable in properly selected patients

Determining suction compression index of expansive soils based on non-linear suction-volumetric strain relationship

Expansive soils have always been problematic in many parts of the United States and the world. This is due to the stresses they exert on buildings' foundations, pavements, and other geotechnical structures. In the United States, volumetric changes due to shrinking and swelling soils cause extensive damage which costs billions of dollars annually. In the state of Oklahoma, expansive soil is widespread and the annual maintenance can cost millions of dollars statewide. The climatic conditions in the state easily allow for soil volume changes. This happens due to the wetting and drying cycles which affect the moisture active zone in unsaturated soils. Suction compression index (?h) is the key parameter that relates volumetric changes to soil suction changes in unsaturated soils. It is a soil property through which heave in expansive soils can be predicted due to the change in soil suction. It can be determined as the slope of the suction-volumetric strain relationship. Since this relationship is essentially nonlinear, the need for a precise ?h determination method has always been crucial. The more accurate ?h is determined, the more accurate soil movements can be predicted and taken care of early in the design stage. Accordingly, more money can be saved from either the repair costs or the initial costs by avoiding over-design. This study proposes an original ?h testing method. The testing method uniquely incorporates volumetric and suction measurements in a new and practical way utilizing simple digital imaging. This makes it convenient for geotechnical engineering practitioners and laboratories to adopt the testing method. The testing method unprecedentedly integrates statistical modeling for determination of incremental h in order to cover the entire nonlinearity of the suction-volumetric strain relationship. This is done by fitting the S-shaped relationship by a well-known class of statistical functions called Cumulative Distribution Functions (CDF). Incremental ?h is estimated by estimating the CDF at every suction value. The appropriateness of using these estimates to describe the suction-volumetric strain relationship is evaluated using the Kolmogorov-Smirnov (K-S) goodness of fit test. Furthermore, 95% confidence intervals of the superposed curves are also used to assess the appropriateness of the CDF estimates. Undisturbed soil specimens from three sites in Oklahoma have been tested. The new testing method is compared against other techniques in the literature and proven reliable results