The Geothermal Probabilistic Cost Model with an Application to a Geothermal Reservoir at Heber, California

A financial accounting model that incorporates physical and institutional uncertainties was developed for geothermal projects. Among the uncertainties it can handle are well depth, flow rate, fluid temperature, and permit and construction times. The outputs of the model are cumulative probability distributions of financial measures such as capital cost, levelized cost, and profit. These outputs are well suited for use in an investment decision incorporating risk. The model has the powerful feature that conditional probability distribution can be used to account for correlations among any of the input variables. The model has been applied to a geothermal reservoir at Heber, California, for a 45-MW binary electric plant. Under the assumptions made, the reservoir appears to be economically viable

Geothermal probabilistic cost study

A tool is presented to quantify the risks of geothermal projects, the Geothermal Probabilistic Cost Model (GPCM). The GPCM model was used to evaluate a geothermal reservoir for a binary-cycle electric plant at Heber, California. Three institutional aspects of the geothermal risk which can shift the risk among different agents was analyzed. The leasing of geothermal land, contracting between the producer and the user of the geothermal heat, and insurance against faulty performance were examined

Complement component C6 deficiency and susceptibility to Neisseria Meningitidis infection

Meningococcal disease remains one of the most serious bacterial infections in both Western and developing countries. Despite recent advances in treatment the mortality rate remains at about 12%.1 There is a group of South Africans who are particularly vulnerable to this disease. They are individuals with genetically determined deficiencies of individual terminal complement proteins, in particular of the sixth component of complement (C6).2 The human complement system forms part of the humeral immune system and consists of a series of proteins.3 The interaction of antigen (such as components of bacterial outer membranes) and antibody leads to activation of the first component C1q, and consequent activation of part or all of the complement cascade. This has a number of biological effects including the formation on the membrane of the membrane attack complex (MAC) from components C5b, C6, C7, C8 and C9. The MAC is able to mediate lysis of some mammalian cells such as red blood cells, as well as lysis of bacteria and certain viruses. This action of complement has been recognised for many years as playing a major role in defence against infection.4 In addition, MAC action is often sublytic on nucleated host cells, and this interaction can sometimes stimulate cellular biosynthesis and act in a pro-inflammatory manner.5 Many other complement proteins, and products of complement activation, also interact with the cellular immune system and the inflammatory system. If activation is caused by pathological processes such as ischaemia, complement can be an important contributor to host tissue necrosis.6 The effects of complement activation are very complex and can be detrimental as well as beneficial

The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

Exposure of Human Lung Cells to Tobacco Smoke Condensate Inhibits the Nucleotide Excision Repair Pathway

Exposure to tobacco smoke is the number one risk factor for lung cancer. Although the DNA damaging properties of tobacco smoke have been well documented, relatively few studies have examined its effect on DNA repair pathways. This is especially true for the nucleotide excision repair (NER) pathway which recognizes and removes many structurally diverse DNA lesions, including those introduced by chemical carcinogens present in tobacco smoke. The aim of the present study was to investigate the effect of tobacco smoke on NER in human lung cells. We studied the effect of cigarette smoke condensate (CSC), a surrogate for tobacco smoke, on the NER pathway in two different human lung cell lines; IMR-90 lung fibroblasts and BEAS-2B bronchial epithelial cells. To measure NER, we employed a slot-blot assay to quantify the introduction and removal of UV light-induced 6–4 photoproducts and cyclobutane pyrimidine dimers. We find a dose-dependent inhibition of 6–4 photoproduct repair in both cell lines treated with CSC. Additionally, the impact of CSC on the abundance of various NER proteins and their respective RNAs was investigated. The abundance of XPC protein, which is required for functional NER, is significantly reduced by treatment with CSC while the abundance of XPA protein, also required for NER, is unaffected. Both XPC and XPA RNA levels are modestly reduced by CSC treatment. Finally, treatment of cells with MG-132 abrogates the reduction in the abundance of XPC protein produced by treatment with CSC, suggesting that CSC enhances proteasome-dependent turnover of the protein that is mediated by ubiquitination. Together, these findings indicate that tobacco smoke can inhibit the same DNA repair pathway that is also essential for the removal of some of the carcinogenic DNA damage introduced by smoke itself, increasing the DNA damage burden of cells exposed to tobacco smoke

Acetylation Regulates WRN Catalytic Activities and Affects Base Excision DNA Repair

Background: The Werner protein (WRN), defective in the premature aging disorder Werner syndrome, participates in a number of DNA metabolic processes, and we have been interested in the possible regulation of its function in DNA repair by post-translational modifications. Acetylation mediated by histone acetyltransferases is of key interest because of its potential importance in aging, DNA repair and transcription. Methodology/Principal Findings: Here, we have investigated the p300 acetylation mediated changes on the function of WRN in base excision DNA repair (BER). We show that acetylation of WRN increases in cells treated with methyl methanesulfonate (MMS), suggesting that acetylation of WRN may play a role in response to DNA damage. This hypothesis is consistent with our findings that acetylation of WRN stimulates its catalytic activities in vitro and in vivo, and that acetylated WRN enhances pol b-mediated strand displacement DNA synthesis more than unacetylated WRN. Furthermore, we show that cellular exposure to the histone deacetylase inhibitor sodium butyrate stimulates long patch BER in wild type cells but not in WRN depleted cells, suggesting that acetylated WRN participates significantly in this process. Conclusion/Significance: Collectively, these results provide the first evidence for a specific role of p300 mediated WRN acetylation in regulating its function during BER