Stepwise development from ideal specifications

Author(s):  
G. Smith
Keyword(s):  
2020 ◽  
Vol 27 (8) ◽  
pp. 698-710
Author(s):  
Roya Cheraghi ◽  
Mahboobeh Nazari ◽  
Mohsen Alipour ◽  
Saman Hosseinkhani

Gene-based therapy largely relies on the vector type that allows a selective and efficient transfection into the target cells with maximum efficacy and minimal toxicity. Although, genes delivered utilizing modified viruses transfect efficiently and precisely, these vectors can cause severe immunological responses and are potentially carcinogenic. A promising method of overcoming this limitation is the use of non-viral vectors, including cationic lipids, polymers, dendrimers, and peptides, which offer potential routes for compacting DNA for targeted delivery. Although non-viral vectors exhibit reduced transfection efficiency compared to their viral counterpart, their superior biocompatibility, non-immunogenicity and potential for large-scale production make them increasingly attractive for modern therapy. There has been a great deal of interest in the development of biomimetic chimeric peptides. Biomimetic chimeric peptides contain different motifs for gene translocation into the nucleus of the desired cells. They have motifs for gene targeting into the desired cell, condense DNA into nanosize particles, translocate the gene into the nucleus and enhance the release of the particle into the cytoplasm. These carriers were developed in recent years. This review highlights the stepwise development of the biomimetic chimeric peptides currently being used in gene delivery.


Author(s):  
Georg Heinze ◽  
Maarten van Smeden ◽  
Laure Wynants ◽  
Ewout Steyerberg ◽  
Ben van Calster

2015 ◽  
Vol 16 (2) ◽  
pp. 189-235 ◽  
Author(s):  
DANIELA INCLEZAN ◽  
MICHAEL GELFOND

AbstractThe paper introduces a new modular action language,${\mathcal ALM}$, and illustrates the methodology of its use. It is based on the approach of Gelfond and Lifschitz (1993,Journal of Logic Programming 17, 2–4, 301–321; 1998,Electronic Transactions on AI 3, 16, 193–210) in which a high-level action language is used as a front end for a logic programming system description. The resulting logic programming representation is used to perform various computational tasks. The methodology based on existing action languages works well for small and even medium size systems, but is not meant to deal with larger systems that requirestructuring of knowledge.$\mathcal{ALM}$is meant to remedy this problem. Structuring of knowledge in${\mathcal ALM}$is supported by the concepts ofmodule(a formal description of a specific piece of knowledge packaged as a unit),module hierarchy, andlibrary, and by the division of a system description of${\mathcal ALM}$into two parts:theoryandstructure. Atheoryconsists of one or more modules with a common theme, possibly organized into a module hierarchy based on adependency relation. It contains declarations of sorts, attributes, and properties of the domain together with axioms describing them.Structuresare used to describe the domain's objects. These features, together with the means for defining classes of a domain as special cases of previously defined ones, facilitate the stepwise development, testing, and readability of a knowledge base, as well as the creation of knowledge representation libraries.


Author(s):  
V. P. Lysenko ◽  
I. S. Chernova

Annotation Purpose. Improving the efficiency of entomophages production by developing innovative approaches for it management. Methods. System approach, intelligent information technologies. Results. Innovative approaches for it management of entomophages production have been developed, which consist of: determining and ranking the factors that have the greatest impact on the quality of entomological products, and factors that lead to substandard products; the creation of structural and parametric complexes for assessing product quality; real-time assessment of the intensity of entomocultures development processes; automation of management abiotic parameters stepwise development of insects (temperature and relative humidity of the box for growing of insects) in real time; determining the quality of entomological products in conditions of incomplete information, taking into account the impact of a combination of abiotic and biotic production parameters; calculation of optimal values of production parameters in conditions of uncertainty; systematization of knowledge about the interaction of heterogeneous parameters in the production of entomophages. Conclusions. The proposed innovative approaches to manage the production of entomophages can increase its efficiency by forming optimal management strategies, using the technological experience of specialists and modern intelligent information technologies in particular, SCADA-systems, fuzzy logic theory and cognitive analysis. Keywords: innovative approaches, production of entomophages, intelligent information technologies.


Author(s):  
Paulius Stankaitis ◽  
Alexei Iliasov ◽  
Tsutomu Kobayashi ◽  
Yamine Aït-Ameur ◽  
Fuyuki Ishikawa ◽  
...  

AbstractThe decentralised railway signalling systems have a potential to increase capacity, availability and reduce maintenance costs of railway networks. However, given the safety-critical nature of railway signalling and the complexity of novel distributed signalling solutions, their safety should be guaranteed by using thorough system validation methods. To achieve such a high-level of safety assurance of these complex signalling systems, scenario-based testing methods are far from being sufficient despite that they are still widely used in the industry. Formal verification is an alternative approach which provides a rigorous approach to verifying complex systems and has been successfully used in the railway domain. Despite the successes, little work has been done in applying formal methods for distributed railway systems. In our research we are working towards a multifaceted formal development methodology of complex railway signalling systems. The methodology is based on the Event-B modelling language which provides an expressive modelling language, a stepwise development and a proof-based model verification. In this paper, we present the application of the methodology for the development and verification of a distributed protocol for reservation of railway sections. The main challenge of this work is developing a distributed protocol which ensures safety and liveness of the distributed railway system when message delays are allowed in the model.


2018 ◽  
Author(s):  
W.-Matthias Leeder ◽  
Fabian Giehler ◽  
Juliane Joswig ◽  
H. Ulrich Göringer

AbstractHumans have evolved a natural immunity against Trypanosoma brucei infections, which is executed by two serum (lipo)protein complexes known as trypanolytic factors (TLF). Active TLF-ingredient is the primate-specific apolipoprotein L1 (ApoL1). The protein has a pore-forming activity that kills parasites by lysosomal and mitochondrial membrane fenestration. Of the many trypanosome subspecies only two are able to counteract the activity of ApoL1, which illustrates its evolutionary optimized design and trypanocidal potency. Here we ask the question whether a synthetic (syn)TLF can be synthesized using the design principles of the natural TLF-complexes but relying on different chemical building blocks. We demonstrate the stepwise development of triterpenoid-peptide conjugates, in which the triterpenoids act as a cell binding, uptake and lysosomal transport-moduls and the synthetic peptide GALA as a pH-sensitive, pore-forming lysolytic toxin. As designed, the conjugate kills infective-stage African trypanosomes through lysosomal lysis demonstrating proof-of-principle for the bioinspired, forward-design of a synTLF.


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