Agency for Science, Technology and Research

About: Agency for Science, Technology and Research is a government organization based out in Singapore, Singapore. It is known for research contribution in the topics: Catalysis & Population. The organization has 16013 authors who have published 24427 publications receiving 832302 citations. The organization is also known as: A*STAR & A-Star.

A Competitive-Cooperative Coevolutionary Paradigm for Dynamic Multiobjective Optimization

Abstract: In addition to the need for satisfying several competing objectives, many real-world applications are also dynamic and require the optimization algorithm to track the changing optimum over time. This paper proposes a new coevolutionary paradigm that hybridizes competitive and cooperative mechanisms observed in nature to solve multiobjective optimization problems and to track the Pareto front in a dynamic environment. The main idea of competitive-cooperative coevolution is to allow the decomposition process of the optimization problem to adapt and emerge rather than being hand designed and fixed at the start of the evolutionary optimization process. In particular, each species subpopulation will compete to represent a particular subcomponent of the multiobjective problem, while the eventual winners will cooperate to evolve for better solutions. Through such an iterative process of competition and cooperation, the various subcomponents are optimized by different species subpopulations based on the optimization requirements of that particular time instant, enabling the coevolutionary algorithm to handle both the static and dynamic multiobjective problems. The effectiveness of the competitive-cooperation coevolutionary algorithm (COEA) in static environments is validated against various multiobjective evolutionary algorithms upon different benchmark problems characterized by various difficulties in local optimality, discontinuity, nonconvexity, and high-dimensionality. In addition, extensive studies are also conducted to examine the capability of dynamic COEA (dCOEA) in tracking the Pareto front as it changes with time in dynamic environments.

Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma.

Abstract: Real-time monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major clinical problem as serial re-biopsy of primary tumours is often not a clinical option. MGMT (O6-methylguanine DNA methyltransferase) and APNG (alkylpurine-DNA-N-glycosylase) are key enzymes capable of repairing temozolomide-induced DNA damages and their levels in tissue are inversely related to treatment efficacy. Yet, serial clinical analysis remains difficult, and, when done, primarily relies on promoter methylation studies of tumour biopsy material at the time of initial surgery. Here we present a microfluidic chip to analyse mRNA levels of MGMT and APNG in enriched tumour exosomes obtained from blood. We show that exosomal mRNA levels of these enzymes correlate well with levels found in parental cells and that levels change considerably during treatment of seven patients. We propose that if validated on a larger cohort of patients, the method may be used to predict drug response in GBM patients. Predicting and monitoring chemotherapy response remains a challenge for glioma treatment. Here the authors show that a microfluidic device can isolate glioma-derived exosomes from patient blood and accurately determine the levels of mRNA of key enzymes important for chemoresponsiveness.

The nuclear lamins: flexibility in function

Abstract: The nuclear lamina is an important structural determinant for the nuclear envelope as a whole, attaching chromatin domains to the nuclear periphery and localizing some nuclear envelope proteins. The major components of the lamina are the A-type and B-type lamins, which are members of the intermediate filament protein family. Whereas the expression of A-type lamins is developmentally regulated, B-type lamins, as a class, are found in all cells. The association of B-type lamins with many aspects of nuclear function has led to the view that these are essential proteins, and there is growing evidence suggesting that they regulate cellular senescence. However, B-type lamins are dispensable in certain cell types in vivo, and neither A-type nor B-type lamins may be required in early embryos or embryonic stem cells. The picture that is beginning to emerge is of a complex network of interactions at the nuclear periphery that may be defined by cell- and tissue-specific functions.

Allelic reprogramming of the histone modification H3K4me3 in early mammalian development

Abstract: Histone modifications are fundamental epigenetic regulators that control many crucial cellular processes. However, whether these marks can be passed on from mammalian gametes to the next generation is a long-standing question that remains unanswered. Here, by developing a highly sensitive approach, STAR ChIP-seq, we provide a panoramic view of the landscape of H3K4me3, a histone hallmark for transcription initiation, from developing gametes to post-implantation embryos. We find that upon fertilization, extensive reprogramming occurs on the paternal genome, as H3K4me3 peaks are depleted in zygotes but are readily observed after major zygotic genome activation at the late two-cell stage. On the maternal genome, we unexpectedly find a non-canonical form of H3K4me3 (ncH3K4me3) in full-grown and mature oocytes, which exists as broad peaks at promoters and a large number of distal loci. Such broad H3K4me3 peaks are in contrast to the typical sharp H3K4me3 peaks restricted to CpG-rich regions of promoters. Notably, ncH3K4me3 in oocytes overlaps almost exclusively with partially methylated DNA domains. It is then inherited in pre-implantation embryos, before being erased in the late two-cell embryos, when canonical H3K4me3 starts to be established. The removal of ncH3K4me3 requires zygotic transcription but is independent of DNA replication-mediated passive dilution. Finally, downregulation of H3K4me3 in full-grown oocytes by overexpression of the H3K4me3 demethylase KDM5B is associated with defects in genome silencing. Taken together, these data unveil inheritance and highly dynamic reprogramming of the epigenome in early mammalian development.

Polymeric Multilayer Capsules in Drug Delivery

Abstract: Recent advances in medicine and biotechnology have prompted the need to develop nanoengineered delivery systems that can encapsulate a wide variety of novel therapeutics such as proteins, chemotherapeutics, and nucleic acids. Moreover, these delivery systems should be "intelligent", such that they can deliver their payload at a well-defined time, place, or after a specific stimulus. Polymeric multilayer capsules, made by layer-by-layer (LbL) coating of a sacrificial template followed by dissolution of the template, allow the design of microcapsules in aqueous conditions by using simple building blocks and assembly procedures, and provide a previously unmet control over the functionality of the microcapsules. Polymeric multilayer capsules have recently received increased interest from the life science community, and many interesting systems have appeared in the literature with biodegradable components and biospecific functionalities. In this Review we give an overview of the recent breakthroughs in their application for drug delivery.