Copper-transporting P-Type ATPase, ATP7A, confers multidrug resistance and its expression is related to resistance to SN-38 in clinical colon cancer

We and others have shown that the copper transporters ATP7A and ATP7B play a role in cellular resistance to cisdiaminedichloroplatinum (II) (CDDP).  In this study, we found that ATP7A transfection of Chinese hamster ovary  cells (CHOK1) and fibroblasts isolated from Menkes disease patients  enhanced resistance not only to CDDP but also to various anticancer drugs, such as vincristine, paclitaxel, 7-ethyl-10- hydroxy-camptothecin (SN-38),  etoposide, doxorubicin, mitoxantron, and 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11). ATP7A preferentially localized
doxorubicin fluorescence to the Golgi apparatus in contrast to the more intense nuclear staining of doxorubicin in the parental cells. Brefeldin A   partially and monensin completely altered the distribution of doxorubicin to the nuclei in the ATP7A-expressing cells. ATP7A expression also enhanced the efflux rates of doxorubicin and SN-38 from cells and increased the uptake of SN-38 in membrane vesicles. These findings strongly suggested that   ATP7A confers multidrug resistance to the cells by compartmentalizing drugs in the Golgi apparatus and by enhancing efflux of these drugs, and the trans-Golgi network has an important role of ATP7A-related drug resistance. ATP7A was expressed in 8 of 34 (23.5%) clinical colon cancer specimens but not in the adjacent normal epithelium. Using the histoculture drug response assay that is useful for the prediction of drug sensitivity of clinical cancers, ATP7A-expressing colon cancer cells were significantly more  resistant to SN-38 than ATP7Anegative cells. Thus, ATP7A confers  resistance to various anticancer agents on cancer cells and might be a good index of drug resistance in clinical colon cancers.

Using mobile agents to detect node compromise in path-based DoS attacks on wireless sensor networks

Wireless sensor networks represent a new generation of real-time  embedded systems with significantly different communication constraints from the traditional networked systems. With their development, a new attack called a path-based DoS (PDoS) attack has appeared. In a PDoS attack, an adversary, either inside or outside the network, overwhelms sensor nodes by flooding a multi-hop endto- end communication path with either replayed packets or injected spurious packets. In this article, we propose a solution using mobile agents which can detect PDoS attacks easily.

Using mobile agents to detect and recover from node compromise in path-based DoS attacks in wireless sensor networks

Wireless sensor networks represent a new generation of real-time embedded systems with significantly different communication constraints from the traditional networked systems. With their development, a new attack called a path-based DoS (PDoS) attack has appeared. In a PDoS attack, an adversary, either inside or outside the network, overwhelms sensor nodes by flooding a multi-hop end-to end communication path with either replayed packets or injected spurious packets. Detection and recovery from PDoS attacks have not been given much attention in the literature. In this article, we propose a solution using mobile agents which can detect PDoS attacks easily and efficiently and recover the compromised nodes.

Environmental factors affecting transcription of the human L1 retrotransposon. I. Steroid hormone-like agents

The L1 retrotransposon has significantly shaped the structure of the human genome. At least 30% of human genome sequence can be attributed to L1 reverse transcriptase activity. There are 105 copies of the human L1 retrotransposon, L1Hs, most of which are defective, although ~8–9x103 are full length. L1Hs elements transpose through an RNA intermediate and transcription is thought to be the rate limiting step in retrotransposition. Because transcription of retrotransposons in a variety of organisms has been shown to respond to environmental stimuli, we investigated the influence of various agents on transcription from two different L1Hs promoters. The activity of the L1Hs promoters was analyzed by transfecting L1Hs-expressing cell lines with plasmids containing the L1Hs promoters fused to the LacZ reporter gene and monitoring expression with a ß-galactosidase assay. Small increases in ß-galactosidase activity were observed with both L1Hs promoters after treatment with serum, testosterone, dihydrotestosterone and organochloride pesticides, indicating that these agents can influence L1Hs transcription.

Marketing research and small travel agents: an exploratory study

The research study reported on in this paper examined the marketing research (MR) orientation of small Australian travel agents. A survey was undertaken involving personal interviews with 91 travel agents in Melbourne, each agency having fewer than 20 employees. Agents were asked about their organisation with regard to MR, which MR activities were undertaken and wich MR techniques were employed. Additional questions gathered data on organisational and individual demographics, and some perceptual and attitudinal data. Although approximately half the respondents had no employee assigned to MR, the majority of agents reported engaging in most of the MR activities nominated, although most agents did not use most of the MR techniques covered in the study. Most general demographics were not related to MR participation, although greater devotion of resources to MR was reflected in more comprehensive usage of MR, and a more positive attitude to the cost-effectiveness of MR in small organisations. The desirability of travel agents considering seriously the role of MR in assisting in clarifying the future options for the sector is noted.

Agents and data mining: mutual enhancement by integration

This paper tells a story of synergism of two cutting edge technologies — agents and data mining. By integrating these two technologies, the power for each of them is enhanced. Integrating agents into data mining systems, or constructing data mining systems from agent perspectives, the flexibility of data mining systems can be greatly improved. New data mining techniques can add to the systems dynamically in the form of agents, while the out-of-date ones can also be deleted from systems at run-time. Equipping agents with data mining capabilities, the agents are much smarter and more adaptable. In this way, the performance of these agent systems can be improved. A new way to integrate these two techniques –ontology-based integration is also discussed. Case studies will be given to demonstrate such mutual enhancement.

Syntheses of Cross-Linking Agents, Molecular Modeling of Oligonucleotides and Polypeptide-Ion Complexes

Each section of this thesis will be subdivided into three parts encompassing all of the research in which I have been involved during the past three years. These will be referred to under the headings "Syntheses:' "Molecular Modeling," and "Cross-linking Efficiencies." Each of these subdivisions may have divisions within them when necessary in order to fully detail the research.

Novel agents that potentially inhibit irinotecan-induced diarrhea

Irinotecan (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) has exhibited clinical activities against a broad spectrum of carcinomas by inhibiting DNA topoisomerase I (Topo I). However, severe and unpredictable dosing-limiting toxicities (mainly myelosuppression and severe diarrhea) hinder its clinical use. The latter consists of early and late-onset diarrhea, occurring within 24 hr or ≥ 24 hr after CPT-11 administration, respectively. This review highlights novel agents potentially inhibiting CPT-11-induced diarrhea, which are designed and tested under guidance of disposition pathways and potential toxicity mechanisms. Early-onset diarrhea is observed immediately after CPT-11 infusion and probably due to the inhibition of acetylcholinesterase activity, which can be eliminated by administration of atropine. Lateonset diarrhea appears to be associated with intestinal exposure to SN-38 (7-ethyl-10-hydroxycamptothecin), the major active metabolite of CPT-11, which may bind to Topo I and induce apoptosis of intestinal epithelia, leading to the disturbance in the absorptive and secretory functions of mucosa. CPT-11 and SN-38 may also stimulate the production of pro-inflammatory cytokines and prostaglandins (PGs), thus inducing the secretion of Na⁺ and Cl^-. Early treatment of severe late-onset diarrhea with oral high-dose loperamide has decreased patient morbidity. Extensive studies have been conducted to identify other potential agents to ameliorate diarrhea in preclinical and clinical models. These include intestinal alkalizing agents, oral antibiotics, enzyme inducers, P-glycoprotein (PgP) inhibitors, cyclooxygenase-2 (COX-2) inhibitors, tumor necrosis factor-agr (TNF-α) inhibitors, or blockers of biliary excretion of SN-38. Further studies are needed to identify the molecular targets associated with CPT-11 toxicity and safe and effective agents for alleviating CPT-11-induced diarrhea.

Making decisions for intelligent agents in procedure descriptive framework

There are many existing and potential industrial and commercial applications for intelligent agents in the literature. The very challenging issue for these applications is to "do what intelligent agents should do". The BDI (beliefs, desires, intentions) architecture is presented to solve this challenge, and it has attracted much attention. The main difficulty for this architecture is the formalization problem. In this paper, we discuss the "procedure descriptive framework", which is a method for formalizing the BDI architecture. We present decision models for intelligent agents in this framework. This research provides a technique for online agents to form beliefs and make decisions according to the current uncertain environment

Decision model for BDI-based intelligent agents

The very challenging issue for intelligent agents is “do what they should do”. The BDI architecture is presented to solve this challenge. The main difficult for this architecture is the formalizing problem. In this paper, we discuss the procedure descriptive framework, which presents a method for formalizing BDI architecture. We a present decision model for intelligent agents in this procedure descriptive framework. This research shows how an agent to generate beliefs and make decisions by using its current beliefs.

A ring-based architectural model for middle agents in agent-based system

In agent-based systems, the performance of middle agents not only relies on the matchmaking algorithms employed by them, but also the architecture that organizes them with suitable organizational structure and coordination mechanism. In this paper, we contribute a framework and develop a couple of middle agents with logical ring organizational structure to match requester agents with service provider agents. The middle agent is of the features of proliferation and self-cancellation according to the sensory input from its environment. The token-based coordination mechanism of middle agents is designed. Two kinds of middle agents, namely, host and duplicate, are designed for promoting the scalability and robustness of agent-based systems. We demonstrate the potentials of the architecture by case study.

A platform for dynamic organization of agents in agent-based systems

In most agent-based systems, different middle agents are employed to increase their flexibility. However, there are still three issues remain unsolved. In centralized architecture with single middle agent, the middle agent itself is a bottleneck and suffers from single point failure; middle agents in distributed architecture lack capability of dynamic organization of agents; The reliability is not strong because of the single point failure and lack of effective architecture. We introduce a platform with ring architectural model to solve all above problems. In the platform, multiple middle agents are dynamically supported for solving the first problem. For solving the second problem, middle agents dynamically manage the registration and cancellation of service provider agents and application teams, each of which includes a set of closely interacting requester agents to complete an independent task. Redundancy middle agent technique is proposed for solving the third problem. All middle agents are of the feature of proliferation and self-cancellation according to the sensory inputs from their environment. For organizing the middle agents effectively, a ring architectural model is proposed. We demonstrate the applicability of the platform by its application and present experimental evidence that the platform is flexible and robust.

Perceived characteristics and pedagogical efficacy of animated conversational agents

We investigated college students' perceptions of a diverse sample of animated conversational agents. We also examined the pedagogical efficacy of those agents. We found that people perceive differences among the agents on several dimensions, such as likeability, and that the agents differ in pedagogical efficacy. However, none of the characteristics that we measured accounted for differences in pedagogical efficacy across the agents. We discuss implications for the field of agent studies with pmiicular emphasis on the creation of pedagogically effective conversational agents and suggest directions for future research.