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

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.

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 Design and Experimental Study of the General Mechanical Pneumatic Combined Seed Metering Device

2021 ◽  
Vol 11 (16) ◽  
pp. 7223
Author(s):  
Dengyu Xiong ◽  
Mingliang Wu ◽  
Wei Xie ◽  
Rong Liu ◽  
Haifeng Luo
Keyword(s):  
High Efficiency ◽  
Cone Angle ◽  
General Purpose ◽  
Optimal Performance ◽  
Air Velocity ◽  
General Properties ◽  
Response Surface Optimization ◽  
Damage Rate ◽  
Air Blowing ◽  
Seed Metering Device

To address the problems of high damage rate, low seeding accuracy, and poor seeding generally in the seeding process, a general-purpose seeding device was designed in this study based on the principle of mechanical pneumatic combined seeding. The air-blowing-type cleaning and seed unloading of the device laid the conditions for precise seeding and flexible seeding. In addition, single-factor experiments were performed on seeds (e.g., soybeans, corn, and rape-seeds) with different particle sizes and shapes to verify the general properties of the seed metering device. A multi-factor response surface optimization experiment was performed by applying soybean seeds as the test object to achieve the optimal performance parameters of the seed metering device. At a seed-clearing air velocity of 16.7 m/s, a seed feeding drum speed of 13.7 r/min, and a hole cone angle of 35.6°, corresponding to the optimal performance index, the qualified index, the replay index, and the missed index reached 97.94%, 0.03%, and 2.03%, respectively. The verification test results are consistent with the optimized ones. As indicated from the results, the seed metering device exhibits good general properties, low damage rate, great precision, and high efficiency; it is capable of meeting general seeding operations of different crop seeds and technically supporting for the reliability and versatility of the seeder.

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