Synthesized cooperative strategies for intelligent multi-robots in a real-time distributed environment : a thesis presented in partial fulfillment of the requirements for the degree of Master of Science in Computer Science at Massey University, Albany, New Zealand

In the robot soccer domain, real-time response usually curtails the development of more complex Al-based game strategies, path-planning and team cooperation between intelligent agents. In light of this problem, distributing computationally intensive algorithms between several machines to control, coordinate and dynamically assign roles to a team of robots, and allowing them to communicate via a network gives rise to real-time cooperation in a multi-robotic team. This research presents a myriad of algorithms tested on a distributed system platform that allows for cooperating multi- agents in a dynamic environment. The test bed is an extension of a popular robot simulation system in the public domain developed at Carnegie Mellon University, known as TeamBots. A low-level real-time network game protocol using TCP/IP and UDP were incorporated to allow for a conglomeration of multi-agent to communicate and work cohesively as a team. Intelligent agents were defined to take on roles such as game coach agent, vision agent, and soccer player agents. Further, team cooperation is demonstrated by integrating a real-time fuzzy logic-based ball-passing algorithm and a fuzzy logic algorithm for path planning. Keywords Artificial Intelligence, Ball Passing, the coaching system, Collaborative, Distributed Multi-Agent, Fuzzy Logic, Role Assignmen

Neutrophil Cyto-Pharmaceuticals Suppressing Tumor Metastasis via Inhibiting Hypoxia-Inducible Factor-1α in Circulating Breast Cancer Cells

Circulating tumor cells (CTCs) are reported as the precursor of tumor metastases, implying that stifling CTCs would be beneficial for metastasis prevention. However, challenges remain for the application of therapies that aim at CTCs due to lack of effective CTC-targeting strategy and sensitive therapeutic agents. Herein, a general CTC-intervention strategy based on neutrophil cyto-pharmaceuticals is proposed for suppressing CTC colonization and metastasis formation. Breast cancer 4T1 cells are infused as the mimic CTCs, and 4T1 cells trapped are first elucidated in neutrophil extracellular traps (NETs) expressing high levels of hypoxia-inducible factor-1α (HIF-1α) due to NET formation and thus promoting tumor cell colonization through enhanced migration, invasion and stemness. After verifying HIF-1α as a potential target for metastasis prevention, living neutrophil cyto-pharmaceuticals (CytPNEs) loaded with HIF-1α inhibitor are fabricated to therapeutically inhibit HIF-1α. It is demonstrated that CytPNEs can specially convey the HIF-1α inhibitor to 4T1 cells according to the inflammatory chemotaxis of neutrophils and down-regulate HIF-1α, thereby inhibiting metastasis and prolonging the median survival of mice bearing breast cancer lung metastasis. The research offers a new perspective for understanding the mechanism of CTC colonization, and puts forward the strategy of targeted intervention of CTCs as a meaningful treatment for tumor metastasis.Fil: Zhang, Ying. China Pharmaceutical University; ChinaFil: Wang, Cong. China Pharmaceutical University; ChinaFil: Li, Weishuo. China Pharmaceutical University; ChinaFil: Tian, Wei. China Pharmaceutical University; ChinaFil: Tang, Chunming. China Pharmaceutical University; ChinaFil: Xue, Lingjing. China Pharmaceutical University; ChinaFil: Lin, Ziming. China Pharmaceutical University; ChinaFil: Liu, Guilai. China Pharmaceutical University; ChinaFil: Liu, Dongfei. China Pharmaceutical University; ChinaFil: Zhou, Ying. China Pharmaceutical University; ChinaFil: Wang, Qianqian. China Pharmaceutical University; ChinaFil: Wang, Xu. China Pharmaceutical University; ChinaFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Yang, Yong. China Pharmaceutical University; ChinaFil: Li, Xianjing. China Pharmaceutical University; ChinaFil: Ju, Caoyun. China Pharmaceutical University; ChinaFil: Zhang, Can. China Pharmaceutical University; Chin

Cargo-selective and adaptive delivery of nucleic acid therapeutics by bola-amphiphilic dendrimers

International audienceNucleic acid therapeutics are becoming an important drug modality, offering the unique opportunity to address “undruggable” targets, respond rapidly to evolving pathogens, and treat diseases at the gene level for precision medicine. However, nucleic acid therapeutics have poor bioavailability and are chemolabile and enzymolabile, imposing the need for delivery vectors. Dendrimers, by virtue of their well-defined structure and cooperative multivalence, represent precision delivery systems. We synthesized and studied bola-amphiphilic dendrimers for cargo-selective and on-demand delivery of DNA and small interfering RNA (siRNA), both important nucleic acid therapeutics. Remarkably, superior performances were achieved for siRNA delivery with the second-generation dendrimer, yet for DNA delivery with the third generation. We systematically studied these dendrimers with regard to cargo binding, cellular uptake, endosomal release, and in vivo delivery. Differences in size both of the dendrimers and their nucleic acid cargos impacted the cooperative multivalent interactions for cargo binding and release, leading to cargo-adaptive and selective delivery. Moreover, both dendrimers harnessed the advantages of lipid and polymer vectors, while offering nanotechnology-based tumor targeting and redox-responsive cargo release. Notably, they allowed tumor- and cancer cell-specific delivery of siRNA and DNA therapeutics for effective treatment in different cancer models, including aggressive and metastatic malignancies, outperforming the currently available vectors. This study provides avenues to engineer tailor-made vectors for nucleic acid delivery and precision medicine

Novel β‑Carboline/Hydroxamic Acid Hybrids Targeting Both Histone Deacetylase and DNA Display High Anticancer Activity via Regulation of the p53 Signaling Pathway

A novel series of hybrids from β-carboline and hydroxamic acid were designed and synthesized. Several compounds (<b>5m</b>, <b>11b</b>–<b>d</b>, and <b>11h</b>) not only exerted significant antiproliferation activity against four human colorectal cancer (CRC) cell lines but also showed histone deacetylase inhibitory effects in vitro. The most potent compound, <b>11c</b>, exhibited anticancer potency sevenfold higher than that of SAHA. <b>11c</b> triggered more significant cancer cell apoptosis than did SAHA by cleavage of both PARP and caspase 3 in a dose-dependent manner. Furthermore, <b>11c</b> simultaneously increased the acetylation of histone H3 and α-tubulin, enhanced expression of DNA damage markers histone H2AX phosphorylation and p-p53 (Ser15), and activated p53 signaling pathway in HCT116 cells. Finally, <b>11c</b> showed low acute toxicity in mice and inhibited the growth of implanted human CRC in mice more potently than did SAHA. Together, <b>11c</b> possessed potent antitumor activity and may be a promising candidate for the potential treatment of human CRC