scholarly journals Autonomous Assembly of Modular Structures in Space and on Extraterrestrial Locations

2005 ◽  
Author(s):  
Dean C. Alhorn
Keyword(s):  
Autonomous Assembly ◽  
Modular Structures

Computational Approaches in Antibody-drug Conjugate Optimization for Targeted Cancer Therapy

2018 ◽  
Vol 18 (13) ◽  
pp. 1091-1109 ◽  
Author(s):  
Rita Melo ◽  
Agostinho Lemos ◽  
Antonio J. Preto ◽  
Jose G. Almeida ◽  
Joao D.G. Correia ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Coarse Grained ◽  
Cytotoxic Agent ◽  
Target Cells ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Cross Correlation Analysis ◽  
Traditional Therapies ◽  
Modular Structures ◽  
Antibody Drug

Cancer has become one of the main leading causes of morbidity and mortality worldwide. One of the critical drawbacks of current cancer therapeutics has been the lack of the target-selectivity, as these drugs should have an effect exclusively on cancer cells while not perturbing healthy ones. In addition, their mechanism of action should be sufficiently fast to avoid the invasion of neighbouring healthy tissues by cancer cells. The use of conventional chemotherapeutic agents and other traditional therapies, such as surgery and radiotherapy, leads to off-target interactions with serious side effects. In this respect, recently developed target-selective Antibody-Drug Conjugates (ADCs) are more effective than traditional therapies, presumably due to their modular structures that combine many chemical properties simultaneously. In particular, ADCs are made up of three different units: a highly selective Monoclonal antibody (Mab) which is developed against a tumour-associated antigen, the payload (cytotoxic agent), and the linker. The latter should be stable in circulation while allowing the release of the cytotoxic agent in target cells. The modular nature of these drugs provides a platform to manipulate and improve selectivity and the toxicity of these molecules independently from each other. This in turn leads to generation of second- and third-generation ADCs, which have been more effective than the previous ones in terms of either selectivity or toxicity or both. Development of ADCs with improved efficacy requires knowledge at the atomic level regarding the structure and dynamics of the molecule. As such, we reviewed all the most recent computational methods used to attain all-atom description of the structure, energetics and dynamics of these systems. In particular, this includes homology modelling, molecular docking and refinement, atomistic and coarse-grained molecular dynamics simulations, principal component and cross-correlation analysis. The full characterization of the structure-activity relationship devoted to ADCs is critical for antibody-drug conjugate research and development.

scholarly journals Nuclear maps and modular structures. I. General properties

1990 ◽  
Vol 88 (2) ◽  
pp. 233-250 ◽  
Author(s):  
Detlev Buchholz ◽  
Claudio D'Antoni ◽  
Roberto Longo
Keyword(s):  
General Properties ◽  
Modular Structures

Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression

2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Current Knowledge ◽  
Nuclear Architecture ◽  
Subnuclear Localization ◽  
Modular Structures

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.

scholarly journals Actuation Characteristics of Basic Body Plans for Soft Modular Pneubotics in Architecture

Buildings ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 106
Author(s):  
Davor Andrić ◽  
Josip Galić ◽  
Karin Šerman
Keyword(s):  
Qualitative Analysis ◽  
Individual Element ◽  
Physical Form ◽  
Basic Body ◽  
Complex Structural ◽  
Modular Structures ◽  
Capacity To Change

The article examines the actuation characteristics of different basic structural schemes—basic body plans—for soft modular pneubotics in architecture are investigated. Eight basic body plans are translated from abstract expressions into their corresponding modular structures and (re)constructed in their physical form using up to 12 soft unit elements in the shape of a cube. Reconstructed basic body plans are then examined through a qualitative analysis of their ability to actuate and change the shape of the structure. Through adaptive manual inflation of an individual element, a group of elements, or all elements at once, motions and transformations are produced and evaluated. The results show that five out of eight basic body plans have higher actuation capacity while three show a less pronounced capacity to change shape. Based on the most pronounced characteristics of the examined basic body plans, design opportunities for potential architectural applications are proposed. These include structures that can self-erect, lift, tilt, bend, change thickness, curvature, etc. What is also shown is that basic body plans could be combined into one complex structural body.

scholarly journals Models of the modular structures of two new heterophyllosilicates related to bornemanite and barytolamprophyllite

2004 ◽  
Vol 60 (a1) ◽  
pp. s196-s196 ◽  
Author(s):  
P. Németh ◽  
G. Ferraris ◽  
I. Dódony ◽  
G. Radnóczi ◽  
A. P. Khomyakov
Keyword(s):  
Modular Structures

Study on life-cycle design for the post mass production paradigm

2000 ◽  
Vol 14 (2) ◽  
pp. 149-161 ◽  
Author(s):  
YASUSHI UMEDA ◽  
AKIRA NONOMURA ◽  
TETSUO TOMIYAMA
Keyword(s):  
Life Cycle ◽  
Mass Production ◽  
Product Life Cycle ◽  
Knowledge Bases ◽  
Life Cycles ◽  
Simulation System ◽  
Product Life ◽  
Cycle Simulation ◽  
Life Cycle Design ◽  
Modular Structures

Environmental issues require a new manufacturing paradigm because the current mass production and mass consumption paradigm inevitably cause them. We have already proposed a new manufacturing paradigm called the “Post Mass Production Paradigm (PMPP)” that advocates sustainable production by decoupling economic growth from material and energy consumption. To realize PMPP, appropriate planning of a product life cycle (design of life cycle) is indispensable in addition to the traditional environmental conscious design methodologies. For supporting the design of a life cycle, this paper proposes a life-cycle simulation system that consists of a life-cycle simulator, an optimizer, a model editor, and knowledge bases. The simulation system evaluates product life cycles from an integrated view of environmental consciousness and economic profitability and optimizes the life cycles. A case study with the simulation system illustrates that the environmental impacts can be reduced drastically without decreasing corporate profits by appropriately combining maintenance, reuse and recycling, and by taking into consideration that optimized modular structures differ according to life-cycle options.

scholarly journals Incremental and Modular Context-sensitive Analysis

2021 ◽  
pp. 1-48
Author(s):  
ISABEL GARCIA-CONTRERAS ◽  
JOSÉ F. MORALES ◽  
MANUEL V. HERMENEGILDO
Keyword(s):  
Global Analysis ◽  
Memory Consumption ◽  
Sensitive Analysis ◽  
Analysis Techniques ◽  
Context Sensitive ◽  
Fine Grained ◽  
Fine Grain ◽  
Modular Analysis ◽  
Modular Algorithm ◽  
Modular Structures

Abstract Context-sensitive global analysis of large code bases can be expensive, which can make its use impractical during software development. However, there are many situations in which modifications are small and isolated within a few components, and it is desirable to reuse as much as possible previous analysis results. This has been achieved to date through incremental global analysis fixpoint algorithms that achieve cost reductions at fine levels of granularity, such as changes in program lines. However, these fine-grained techniques are neither directly applicable to modular programs nor are they designed to take advantage of modular structures. This paper describes, implements, and evaluates an algorithm that performs efficient context-sensitive analysis incrementally on modular partitions of programs. The experimental results show that the proposed modular algorithm shows significant improvements, in both time and memory consumption, when compared to existing non-modular, fine-grain incremental analysis techniques. Furthermore, thanks to the proposed intermodular propagation of analysis information, our algorithm also outperforms traditional modular analysis even when analyzing from scratch.

Lateral Load Path Analysis: Practical Methods for Light-Frame Modular Structures

2018 ◽  
Vol 24 (4) ◽  
pp. 04018027
Author(s):  
Thanh Q. Huynh ◽  
Rakesh Gupta ◽  
Thomas H. Miller ◽  
Michael C. Lewis
Keyword(s):  
Path Analysis ◽  
Lateral Load ◽  
Load Path ◽  
Modular Structures

Biological Design Principles of Complex Feedback Modules in the E. coli Ammonia Assimilation System

2011 ◽  
Vol 18 (1) ◽  
pp. 53-90 ◽  
Author(s):  
Koichi Masaki ◽  
Kazuhiro Maeda ◽  
Hiroyuki Kurata
Keyword(s):  
Feedback Control ◽  
Design Principles ◽  
Cellular Systems ◽  
Fine Tuning ◽  
Ammonia Assimilation ◽  
Control Module ◽  
E Coli ◽  
Biological Design ◽  
Modular Structures ◽  
Assimilation System

To synthesize natural or artificial life, it is critically important to understand the design principles of how biochemical networks generate particular cellular functions and evolve complex systems in comparison with engineering systems. Cellular systems maintain their robustness in the face of perturbations arising from environmental and genetic variations. In analogy to control engineering architectures, the complexity of modular structures within a cell can be attributed to the necessity of achieving robustness. To reveal such biological design, the E. coli ammonia assimilation system is analyzed, which consists of complex but highly structured modules: the glutamine synthetase (GS) activity feedback control module with bifunctional enzyme cascades for catalyzing reversible reactions, and the GS synthesis feedback control module with positive and negative feedback loops. We develop a full-scale dynamic model that unifies the two modules, and we analyze its robustness and fine tuning with respect to internal and external perturbations. The GS activity control is added to the GS synthesis module to improve its transient response to ammonia depletion, compensating the tradeoffs of each module, but its robustness to internal perturbations is lost. These findings suggest some design principles necessary for the synthesis of life.

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