Generalized crystallography and bound-water modular structures determining morphogenesis and size of biosystems

The mathematical model of wood drying based on detailed transport phenomena considering both heat and moisture transfer have been offered in article. The adjustment of this model to the drying process of papermaking is carried out for the range of moisture content corresponding to the period of drying in which vapour movement and bound water diffusion in the web are possible. By averaging as the desired models are obtained sequence of the initial value problems for systems of two nonlinear first order ordinary differential equations.

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

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180731165222 ◽

2018 ◽

Vol 18 (13) ◽

pp. 1091-1109 ◽

Cited By ~ 2

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.

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Nuclear maps and modular structures. I. General properties

Journal of Functional Analysis ◽

10.1016/0022-1236(90)90104-s ◽

1990 ◽

Vol 88 (2) ◽

pp. 233-250 ◽

Cited By ~ 35

Author(s):

Detlev Buchholz ◽

Claudio D'Antoni ◽

Roberto Longo

Keyword(s):

General Properties ◽

Modular Structures

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

Biochemistry and Cell Biology ◽

10.1139/o05-062 ◽

2005 ◽

Vol 83 (4) ◽

pp. 535-547 ◽

Cited By ~ 7

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.

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Elucidating the Molecular Mechanisms for the Interaction of Water with Polyethylene Glycol-Based Hydrogels: Influence of Ionic Strength and Gel Network Structure

Polymers ◽

10.3390/polym13060845 ◽

2021 ◽

Vol 13 (6) ◽

pp. 845

Author(s):

Xin Yang ◽

Bronwin Dargaville ◽

Dietmar Hutmacher

Keyword(s):

Polyethylene Glycol ◽

Ionic Strength ◽

Molecular Mechanisms ◽

Repeat Unit ◽

Bound Water ◽

Weight Fraction ◽

Swelling Ratio ◽

Polyethylene Glycol Diacrylate ◽

Glycol Diacrylate ◽

Hydrogel System

The interaction of water within synthetic and natural hydrogel systems is of fundamental importance in biomaterial science. A systematic study is presented on the swelling behavior and states of water for a polyethylene glycol-diacrylate (PEGDA)-based model neutral hydrogel system that goes beyond previous studies reported in the literature. Hydrogels with different network structures are crosslinked and swollen in different combinations of water and phosphate-buffered saline (PBS). Network variables, polyethylene glycol (PEG) molecular weight (MW), and weight fraction are positively correlated with swelling ratio, while “non-freezable bound water” content decreases with PEG MW. The presence of ions has the greatest influence on equilibrium water and “freezable” and “non-freezable” water, with all hydrogel formulations showing a decreased swelling ratio and increased bound water as ionic strength increases. Similarly, the number of “non-freezable bound water” molecules, calculated from DSC data, is greatest—up to six molecules per PEG repeat unit—for gels swollen in PBS. Fundamentally, the balance of osmotic pressure and non-covalent bonding is a major factor within the molecular structure of the hydrogel system. The proposed model explains the dynamic interaction of water within hydrogels in an osmotic environment. This study will point toward a better understanding of the molecular nature of the water interface in hydrogels.

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Description of the concrete carbonation process with adjusted depth-resolved thermogravimetric analysis

Journal of Thermal Analysis and Calorimetry ◽

10.1007/s10973-021-10966-1 ◽

2021 ◽

Author(s):

Nico Vogler ◽

Philipp Drabetzki ◽

Mathias Lindemann ◽

Hans-Carsten Kühne

Keyword(s):

Calcium Hydroxide ◽

Bound Water ◽

Reference Method ◽

Microscopic Analysis ◽

Limestone Powder ◽

Gravimetric Analysis ◽

Sample Material ◽

Accelerated Carbonation ◽

Temperature Range ◽

Carbonation Process

AbstractThe thermal gravimetric analysis (TG) is a common method for the examination of the carbonation progress of cement-based materials. Unfortunately, the thermal properties of some components complicate the evaluation of TG results. Various hydrate phases, such as ettringite (AFt), C–S–H and AFm, decompose almost simultaneously in the temperature range up to 200 °C. Additionally, physically bound water is released in the same temperature range. In the temperature range between 450 °C and 600 °C, the decomposition of calcium hydroxide and amorphous or weakly bound carbonates takes place simultaneously. Carbonates, like calcite, from limestone powder or other additives may be already contained in the noncarbonated sample material. For this research, an attempt was made to minimise the influence of these effects. Therefore, differential curves from DTG results of noncarbonated areas and areas with various states of carbonation of the same sample material were calculated and evaluated. Concretes based on three different types of cement were produced and stored under accelerated carbonation conditions (1% CO2 in air). The required sample material was obtained by cutting slices from various depths of previously CO2-treated specimen and subsequent grinding. During the sample preparation, a special attention was paid that no additional carbonation processes took place. As reference method for the determination of the carbonation depth, the sprayed application of phenolphthalein solution was carried out. Microscopic analysis was examined to confirm the assumptions made previously. Furthermore, the observed effect of encapsulation of calcium hydroxide by carbonates caused by the accelerated carbonation conditions was examined more closely.

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Synchrotron radiation macromolecular crystallography: our science and spin offs

Acta Crystallographica Section A Foundations and Advances ◽

10.1107/s2053273314099896 ◽

2014 ◽

Vol 70 (a1) ◽

pp. C10-C10

Author(s):

John Helliwell

Keyword(s):

Synchrotron Radiation ◽

Protein Complexes ◽

Bound Water ◽

Water Structure ◽

Public Understanding ◽

Anomalous Scattering ◽

Structural Studies ◽

Macromolecular Crystallography ◽

Time Resolved ◽

Chemical Crystallography

I will give an overview of synchrotron radiation (SR) in macromolecular crystallography (MX) instrumentation, methods and applications from the early days to the present, including the evolution of SR sources and on to the `ultimate storage ring'. The build of dedicated beamlines for resonant anomalous scattering, large unit cells, ever smaller crystals and studies up to ultra-high resolution are core benefits. Results include a high output of PDB depositions, the successful use of microcrystals, pushing the frontiers of using high and low photon energies and time-resolved structural studies at even sub-nanosecond resolutions. These intensively physics based developments will be complemented by biological and chemical crystallography research results, encompassing catalysis and marine coloration, as well as the public understanding of our science and its impacts. Spin off benefits include services to the pharmaceutical industry and helping develop chemical crystallography uses of SR. The development of the Laue method with SR has led to pioneering spin off developments in neutron MX, including transfer of the well validated Daresbury Laue software to various neutron facilities worldwide. Neutron MX is gathering pace as new instrumentation and dedicated sample preparation facilities are in place at reactor and spallation neutron sources; smaller samples and much larger molecular weight protein complexes are now feasible for investigation so as to establish their protonation states and bound water structure. With the X-ray lasers, closely linked to the SR developments, we anticipate the use of ever smaller samples such as nanocrystals, nanoclusters and single molecules, as well as opening up femtosecond time-resolved diffraction structural studies. At the SR sources, a very high throughput assessment for the best crystal samples and tackling sub-micron crystals will become widespread.

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On biological signaling

Zeitschrift für Naturforschung A ◽

10.1515/zna-2020-0070 ◽

2020 ◽

Vol 75 (6) ◽

pp. 507-509 ◽

Cited By ~ 1

Author(s):

Günter Nimtz ◽

Horst Aichmann

Keyword(s):

Phase Transition ◽

Alternative Model ◽

Pulse Propagation ◽

Membrane Surface ◽

Bound Water ◽

Theoretical Description ◽

Lyotropic Liquid Crystal ◽

Local Phase ◽

Electric Action ◽

Nerve Pulse

AbstractPresently, nerve pulse propagation is understood to take place by electric action pulses. The theoretical description is given by the Hodgkin-Huxley model. Recently, an alternative model was proclaimed, where signaling is carried out by acoustic solitons. The solitons are built by a local phase transition in the lyotropic liquid crystal (LLC) of a biologic membrane. We argue that the crystal structure arranging hydrogen bonds at the membrane surface do not allow such an acoustic soliton model. The bound water is a component of the LLC and the assumed phase transition represents a negative entropy step.

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