The role of APC activators Cdc20p and Cdh1p in regulating mitosis and morphogenesis in C. albicans

Candida albicans is an important fungal pathogen of humans, and its ability to switch between different cell morphologies, including yeast, pseudohyphae and hyphae, is critical for virulence. The cell cycle plays an important, yet poorly understood, role in regulating cellular morphogenesis. Our previous work demonstrated that blocking the yeast cell cycle in mitosis, through depletion of the polo-like kinase Cdc5p, resulted in polarized growth of the yeast bud, producing filamentous cells that were distinct from pseudohyphae or true hyphae. Polarized growth was partially dependent on the spindle checkpoint factor Bub2p, suggesting that checkpoint-activated growth occurs in C. albicans . In contrast, similar checkpoint activation leads to cessation of cell proliferation in most other systems. In order to elucidate how mitotic progression and spindle checkpoints are linked to morphogenesis, a better understanding of the basic regulation of mitosis is required. To this end, we characterized homologues of Cdc20p and Cdh1p, which are targets of the spindle checkpoint and activators of the ubiquitin ligase anaphase-promoting complex (APC), a major regulator of mitotic progression in most systems. Cdc20p and Cdh1p were important for the metaphase-to-anaphase transition and mitotic exit, similar to their counterparts in S. cerevisiae , but strongly influenced morphogenesis in a different manner. Deletion of CDH1 resulted in a pleiotropic phenotype, including some enlarged yeast cells, while absence of the same factor in S. cerevisiae produced small cells. Absence of Cdc20p produced highly polarized yeast buds that resembled Cdc5p-depleted cells, in contrast to the large doublets resulting from loss of Cdc20p in S. cerevisiae . Overexpression of CDC20 in Cdc5p-depleted cells partially suppressed the cell cycle defect, suggesting that Cdc20p may be downstream of Cdc5p. However, polarized growth was not abolished. Deletion of the putative Cdc20p-binding and spindle checkpoint factor Mad2p partially compromised polarized growth in Cdc5p-depleted cells, implying that Mad2p may play a role in linking Cdc5p function with Cdc20p. Deletion of CDH1 had no effect on Cdc5p-dependent polarization, suggesting that Cdh1p is dispensible for the process. While Cdc20p was not required for serum-induced hyphal growth, some cells lacking Cdh1p were not able to form hyphae, yet invaded agar more readily than control cells, suggesting a complex role for this factor in regulating polarized growth. Thus, we provide genetic evidence that Cdc20p and Cdh1p play important roles in regulating mitosis and morphogenesis in C. albicans , but in a different manner than their homologues in S. cerevisiae . Our results extend our knowledge of the regulatory circuit governing mitosis in C. albicans and the potential pathway underlying checkpoint-activated polarized growth

Smart Grid as a Service: A Discussion on Design Issues

Smart grid allows the integration of distributed renewable energy resources into the conventional electricity distribution power grid such that the goals of reduction in power cost and in environment pollution can be met through an intelligent and efficient matching between power generators and power loads. Currently, this rapidly developing infrastructure is not as “smart” as it should be because of the lack of a flexible, scalable, and adaptive structure. As a solution, this work proposes smart grid as a service (SGaaS), which not only allows a smart grid to be composed out of basic services, but also allows power users to choose between different services based on their own requirements. The two important issues of service-level agreements and composition of services are also addressed in this work. Finally, we give the details of how SGaaS can be implemented using a FIPA-compliant JADE multiagent system

Chinese Herbal Medicine Therapy and the Risk of Mortality for Chronic Hepatitis B Patients with Concurrent Liver Cirrhosis: a Nationwide Population-Based Cohort Study

Chronic hepatitis B (CHB) is increasingly recognized as a public health problem in Taiwan. After affected patients are diagnosed with contaminant liver cirrhosis (LC), adverse clinical outcomes, especially death, are common. This study aimed to investigate the effect of Chinese herbal medicine (CHM), an essential branch of Traditional Chinese medicine (TCM), on the mortality risk among CHB patients with contaminant LC. This longitudinal cohort study used the Taiwanese National Health Insurance Research Database to identify 1522 patients 20–70 years of age with newly diagnosed CHB with LC during 1998–2007. Among them, 508 (33.37%) had received CHM products after the onset of CHB (CHM users), and the remaining 1014 patients (66.63%) were designated as a control group (non-CHM users). All enrollees were followed until the end of 2012 to determine deaths during the study period. We applied the Cox proportional hazards regression model to compute the hazard ratio for the association of CHM use and the subsequent risk of death. During the follow-up period, 156 CHM users and 493 non-CHM users died. After controlling for potential confounders, CHM users were found to have a significantly reduced risk of death compared with non-CHM users by 56%, and the effect was predominantly observed among those treated with CHM for \u3e 180 days. CHM therapy lowered the risk of death among CHB patients with contaminant LC, which supported CHM might provide further treatment options for those with chronic liver diseases

Design of Scalable Continuous Media Servers with Dynamic Replication

Multimedia applications place high demands for quality-of-service (QoS), performance, and reliability on systems. These stringent requirements make design of cost-effective and scalable systems difficult. Therefore efficient adaptive and dynamic resource management techniques in conjunction with data placement techniques can be of great help in improving performance, scalability and reliability of such systems. In this paper, we first focus on data placement. In the recent past, a great deal of work has focused on "wide" data striping as a way of dealing with load imbalance problems caused by skews in data access patterns. Another approach to dealing with load imbalance problems is replication. The appropriate compromise between the degree of striping and the degree of replication is key to the design of scalable continuous media (CM) servers. In this work we focus on evaluation of this compromise in the context of a hybrid CM server design. Changes in data access patterns lead to other questions: (1) when should the system alter the number of copies of a CM object, and (2) how to accomplish this change. We address (1) through an adaptive threshold-based approach, and we use dynamic replication policies in conjunction with a mathematical model of user behavior to address (2). We do this without any knowledge of data access patterns and with provisions for full use of VCR functionality. Through a performance study, we show that not only does the use of this mathematical model in conjunction with dynamic resource management policies improves the system's performance but that it also facilitates reduced sensitivity to changes in:(a) workload characteristics, (b) skewness of data access patterns, and (c) frequency of changes in data access patterns. We believe that not only is this a desirable property for a CM server, in general, but that furthermore, it suggests the usefulness of these techniques across a wide range of continuous media applications. (Cross-referenced as UMIACS-TR-2001-21