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Candida glabrata is an opportunistic human pathogen that is increasingly associated with candidemia, owing in part to the intrinsic and acquired high tolerance the organism exhibits for the important clinical antifungal drug fluconazole. This elevated fluconazole resistance often develops through gain-of-function mutations in the zinc cluster-containing(More)
Cryptococcus neoformans is a pathogen that is the most common cause of fungal meningitis. As with most fungal pathogens, the most prevalent clinical antifungal used to treat Cryptococcosis is orally administered fluconazole. Resistance to this antifungal is an increasing concern in treatment of fungal disease in general. Our knowledge of the specific(More)
The fungal pathogen Candida glabrata is an emerging cause of candidiasis in part owing to its robust ability to acquire tolerance to the major clinical antifungal drug fluconazole. Similar to the related species Candida albicans, C. glabrata most typically gains azole tolerance via transcriptional induction of a suite of resistance genes, including a locus(More)
In yeast cells such as those of Saccharomyces cerevisiae, expression of ATP-binding cassette (ABC) transporter proteins has been found to be increased and correlates with a concomitant elevation in azole drug resistance. In this study, we investigated the roles of two Aspergillus fumigatus proteins that share high sequence similarity with S. cerevisiae(More)
The filamentous fungus Aspergillus fumigatus is an important opportunistic pathogen that can cause high mortality levels in susceptible patient populations. The increasing dependence on antifungal drugs to control A. fumigatus has led to the inevitable acquisition of drug-resistant forms of this pathogen. In other fungal pathogens, drug resistance is often(More)
A critical risk to the continued success of antifungal chemotherapy is the acquisition of resistance; a risk exacerbated by the few classes of effective antifungal drugs. Predictably, as the use of these drugs increases in the clinic, more resistant organisms can be isolated from patients. A particularly problematic form of drug resistance that routinely(More)
Deletants of the sphingolipid biosynthetic pathway genes FEN1 and SUR4 of Saccharomyces cerevisiae, as well as deletants of their orthologs in Candida albicans, were found to be 2- to 5-fold-more sensitive to amphotericin B (AmB) than parent strains. The inhibition of sphingolipid biosynthesis in parent strains by myriocin sensitized them to AmB, which can(More)
Candida albicans lacks the ability to survive within its mammalian host in the absence of endogenous glutathione biosynthesis. To examine the ability of this yeast to utilize exogenous glutathione, we exploited the organic sulfur auxotrophy of C. albicans met15Δ strains. We observed that glutathione is utilized efficiently by the alternative pathway of(More)
This paper addresses the Hybrid Flow Shop (HFS) scheduling problems to minimize the total work-in-process inventory. Job scheduling problems are one of the oldest and real world combinational optimization problems. It is multi objective and complex in nature. There exist some criteria that must be taken into consideration when evaluating the quality of the(More)
This paper develops an artificial neural network (ANN) model to forecast the optimum level of raw materials inventory as a function of product demand, manufacturing lead-time, supplier reliability, material holding cost, and material cost. The model selects a feed-forward back-propagation ANN with twelve hidden neurons as the optimum network. We test the(More)