Effect of curing on water diffusivities in acrylate free films as measured via a sorption technique

Studies were performed to investigate the effect of curing on the diffusion coefficients of water, as measured via the sorption technique, in acrylate polymeric films. The mathematical model selected for obtaining diffusion constants from the vapor-phase sorption studies was derived from the longtime Fourier equation used for diffusion into a planar sheet. For Eudragit NE films, the diffusion coefficients of water decreased continuously until a constant minimum value was reached. Diffusion coefficients in Eudragit RS films decreased initially but increased beyond 4 hours of curing at 70δC and 90°C. This latter result suggested the possible evaporation of plasticizer, which also results in a more dramatic increase in glass transition temperature with curing for the Eudragit RS free film in comparison to the Eudragit NE free film. Such loss of plasticizer could also lead to the formation of molecular-scale channels within the films, which would result in increased film permeability. To verify this proposed explanation, the amounts of triethyl citrate plasticizer in Eudragit RS free films were determined using Fourier-transform infrared spectrophotometry. An optimal curing condition was predicted for Eudragit NE and Eudragit RS films based upon the curing conditions at which a minimum value of the diffusion coefficient was reached. Published: August 31, 2007     

The physical state of quick-frozen membranes and lipids

Lipid bilayers and biomembranes produce nearly identical calorimeter scans regardless of whether they are slowly cooled under near-equilibrium conditions or rapidly frozen at rates used in freeze-fracture electron microscopy. Except for the melting of ice at 273 K, for both cooling regimens no significant thermal events occur from 100 K to the usual gel to liquid crystal transition. The gel to liquid crystal transition itself is somewhat altered by rapid cooling when bilayers contain mixed lipid species. Combined with X-ray diffraction studies, the results indicate that quickly frozen bilayers are crystalline, but that the crystalline domains are quite small or otherwise disordered. In contrast to the behavior of lipids in bilayers, hexagonal-phase calcium cardiolipid easily forms a glass upon cooling.     

The Darwinian revolution as viewed by a philosophical biologist

Darwin proclaimed his own work revolutionary. His revolution, however, is still in progress, and the changes that are going on are reflected in the contemporary historical and philosophical literature, including that written by scientists. The changes have taken place at different levels, and have tended to occur at the more superficial ones. The new ontology that arose as a consequence of the realization that species are individuals at once provides an analytical tool for explaining what has been happening and an example of the kind of changes that seem in order. It provides a clear distinction between the roles of history and of laws of nature. Pre-Darwinian evolution was superficial in the sense that it treated change as either as something pre-ordained or else due to timeless laws of nature, rather than historical contingency. Darwinism puts the ontological emphasis upon concrete, particular things (individuals) and therefore delegitimizes both essentialistic and teleological ways of thinking. However, traditional ways of thinking have persisted, if not explicitly, then often as assumptions and procedures that are merely implicit or even unconscious. As a result, anti-evolutionary attitudes continue to influence the practice of evolutionary biology as well as the study of its history and philosophy.     

小鼠卵巢组织的超速冻存法研究

目的　本实验通过对小鼠卵巢组织进行冻存研究 ,掌握卵巢的低温生物学特性 ,摸索出一种简便有效的组织器官冻存法 ,为卵巢移植及器官冷冻提供有用的技术方法。方法　通过对小鼠卵巢组织进行慢速程序法与快速液氮蒸汽法冻存 ,比较分析了不同方法所需保护剂种类、浓度、渗透平衡时间。采用对解冻后卵巢组织超微结构观察、组织化学染色、激素测定及自体、异体移植后动情期的恢复作为评价指标。结果与结论　通过上述实验表明用同种冷冻保护剂 ,液氮蒸汽法冻存的卵巢组织超微结构保存良好 ;组织化学染色示其活性与程序法冻存组织相同 ;自体、异体移植后 ,小鼠动情周期的恢复率及血清雌二醇水平各项指标均与慢速程序法冷冻无显著性差异     

Carbonic anhydrase IX as a novel candidate in liquid biopsy

Abstract

Among the diagnostic techniques for the identification of tumour biomarkers, the liquid biopsy is considered one that offers future research on precision diagnosis and treatment of tumours in a non-invasive manner. The approach consists of isolating tumor-derived components, such as circulating tumour cells (CTC), tumour cell-free DNA (ctDNA), and extracellular vesicles (EVs), from the patient peripheral blood fluids. These elements constitute a source of genomic and proteomic information for cancer treatment. Within the tumour-derived components of the body fluids, the enzyme indicated with the acronym CA IX and belonging to the superfamily of carbonic anhydrases (CA, EC 4.2.1.1) is a promising aspirant for checking tumours. CA IX is a transmembrane-CA isoform that is strongly overexpressed in many cancers being not much diffused in healthy tissues except the gastrointestinal tract. Here, it is summarised the role of CA IX as tumour-associated protein and its putative relationship in liquid biopsyfor diagnosing and monitoring cancer progression.     

The Japanese knotweed invasion viewed as a vast unintentional hybridisation experiment

Chromosome counts of plants grown from open-pollinated seed from Japanese knotweed around the world have revealed the presence of extensive hybridisation with both native and other introduced taxa. These hybrids fit into three categories: inter- and intraspecific hybrids involving the taxa of Fallopia section Reynoutria (giant knotweeds), hybrids between Japanese knotweed and F. baldschuanica (Regel) Holub and hybrids between Japanese knotweed and the Australasian endemics of the genus Muehlenbeckia. In this minireview, the viability of the different classes of hybrid and the potential threats they pose are discussed in the context of recent examples of allopolyploid speciation, which generally involve hybridisation between a native and an alien species. Such wide hybridisations also challenge accepted taxonomic classifications. Japanese knotweed s.l. provides a fascinating example of the interplay between ploidy level, hybridisation and alien plant invasion. The octoploid (2n=88) Fallopia japonica var. japonica (Houtt.) Ronse Decraene is a single female clone throughout much of its adventive range, and provides an ideal system for investigating the potential for wide hybridisation.     

Evolution of dispersal in a stepping-stone population with overlapping generations

We use Hamilton's inclusive fitness method to calculate the evolutionarily stable dispersal rate in 1- and 2-dimensional stepping-stone populations. This extends previous results by introducing a positive probability for adults to survive into the next generation and breed again. Relatedness between nearby individuals generally decreases with increasing survival, decreasing competition with kin and favouring greater dispersal rates.     

History of phage research as viewed by a European

Abstract: The history of phage research as the origin of molecular biology is related as seen by a scientist located at that critical time in Geneva. The preponderant influence of Max Delbrück on these developments is traced as a consequence of his personal charisma. Jean Weigle, former professor of experimental physics in Geneva and later research fellow with Delbrück, acted as an important ambassador to the European groups.     

A Strong to Fragile Transition in a Model of Liquid Silica

Abstract

The transport properties of an ionic model for liquid silica [1] at high temperatures and pressure are investigated using molecular dynamics simulations. With increasing pressure, a clear change from “strong” to “fragile” behaviour (according to Angell's classification of glass-forming liquids) is observed, albeit only on the small viscosity range that can be explored in MD simulations. This change is related to structural changes, from an almost perfect four-fold coordination to an imperfect five or six-fold coordination.     

Description of hydration free energy density as a function of molecular physical properties

A method to calculate the solvation free energy density (SFED) at any point in the cavity surface or solvent volume surrounding a solute is proposed. In the special case in which the solvent is water, the SFED is referred to as the hydration free energy density (HFED). The HFED is described as a function of some physical properties of the molecules. These properties are represented by simple basis functions. The hydration free energy of a solute was obtained by integrating the HFED over the solvent volume surrounding the solute, using a grid model. Of 34 basis functions that were introduced to describe the HFED, only six contribute significantly to the HFED. These functions are representations of the surface area and volume of the solute, of the polarization and dispersion of the solute, and of two types of electrostatic interactions between the solute and its environment. The HFED is described as a linear combination of these basis functions, evaluated by summing the interaction energy between each atom of the solute with a grid point in the solvent, where each grid point is a representation of a finite volume of the solvent. The linear combination coefficients were determined by minimizing the error between the calculated and experimental hydration free energies of 81 neutral organic molecules that have a variety of functional groups. The calculated hydration free energies agree well with the experimental results. The hydration free energy of any other solute molecule can then be calculated by summing the product of the linear combination coefficients and the basis functions for the solute.     

Inclusion of solvation free energy with molecular mechanics energy: alanyl dipeptide as a test case.

A combined force field of molecular mechanics and solvation free energy is tested by carrying out energy minimization and molecular dynamics on several conformations of the alanyl dipeptide. Our results are qualitatively consistent with previous experimental and computational studies, in that the addition of solvation energy stabilizes the C5 conformation of the alanyl dipeptide relative to the C7.     

Conservation of major leg arteries when used as recipient supply for a free flap.

The potential hazards of using proximal segments of leg arteries for end-to-end anastomosis to vessels in free flaps are examined, and alternatives are proposed. The convservation of the major tibial arteries seems highly desirable, to minimize any subsequent development of ischemic complications. Turning a free flap upside down moves the anastomosis to the distal part of the extremity, thus conserving most of the muscular branches of the recipient artery. Cutting the recipient artery distally and bending it back in recurrent fashion also allows for easy end-to-end anastomosis, with many technical advantages.     

Calculation of the free energy of association for protein complexes.

We have developed a method for calculating the association energy of quaternary complexes starting from their atomic coordinates. The association energy is described as the sum of two solvation terms and an energy term to account for the loss of translational and rotational entropy. The calculated solvation energy, using atomic solvation parameters and the solvent accessible surface areas, has a correlation of 96% with experimentally determined values. We have applied this methodology to examine intermediates in viral assembly and to assess the contribution isomerization makes to the association energy of molecular complexes. In addition, we have shown that the calculated association can be used as a predictive tool for analyzing modeled molecular complexes.     

The Turing-Child energy field as a driver of early mammalian development

The equivalence of the early mammalian cells, of importance in assisted reproductive technologies (ART), is considered. It is suggested that this controversial topic can be settled by finding whether the cells are distinguished by the Turing-Child (TC) field, as expressed for example by patterns of mitochondrial activity. The division of the pronuclear embryo is driven by a symmetrical bipolar TC pattern whose experimental shape and chemical nature is predicted by TC theory. This bipolar pattern drives the subsequent cell divisions too, and according to present experimental results all cells are equivalent until compaction since they are not distinguished by the TC field in normal development. Interphase cells exhibit homogeneous mitochondrial activity, or perinuclear, or perinuclear and cortical activity, and these patterns too and the rotational symmetry observed are predicted by TC theory. The first differentiation, into an inner mass cell and the trophectoderm, as well as the formation of cell polarity in the trophectoderm are considered. It is suggested that these two events are driven by a peripheral spherical shell of high energy metabolism in the morula; such a shell is predicted by TC theory in a compacted multicellular sphere whose cells are connected by gap junctions. The experimental patterns of mitochondrial activity in unfertilized oocytes exhibit rotational symmetry or polarity. The shape and the chemical nature of these patterns also are predicted and explained by TC theory in a sphere. The change in the spatial pattern of mitochondrial activity with development is attributed to a change in the spatial pattern of mitochondrial activity and not to physical translocation of mitochondria. The experimental finding that these spatial patterns of mitochondrial activity are observed only in live and not in dead biological material is explained by the TC pattern being biology's unique and universal dissipative structure that requires ongoing specific biochemical reactions and energy dissipation.     

8 Using pseudorotation as a reaction coordinate in free energy simulations of nucleic acids

Backbone sugar groups are central components of nucleic acids. The conformations of the ribose/deoxyribose can be elegantly described using the concept of pseudorotation (Altona and Sundaralingam, 1972), and are dominated by the C2′- and C3′-endo conformers. The free energy barrier of the transition between these two major puckering modes can be probed by NMR relaxation experiments (Johnson and Hoogstraten, 2008), but an atomic picture of the transition path per se is only available for several truncated nucleoside analogues (Brameld & Goddard III, 1999). Here, we implemented a new free energy simulation method for Molecular Dynamics simulations using pseudorotation as the reaction coordinate (Cremer and Pople, 1975). This allowed us to compute the free energy landscape of a complete pseudorotation cycle. The free energy landscape revealed not only the relative stability of C2′- and C3′-endo conformers, but also the main transition path and its free energy barrier. As a validation of our new approach, we calculated free energy surface of the pseudorotation of guanosine monophosphate. The free energy surface revealed that the C2′-endo conformation is ?1?kcal/mol that is more stable and the free energy barrier for the transition is 4.5–5?kcal/mol. These are in excellent agreement with previous NMR measurements (Zhang et al., 2012; Röder et al., 1975). We have further applied this method to other systems that are important in pre-biotic chemistry, including an RNA duplex with unique 2′, 5′-phosphodiester linkages.     

Shape of the free energy barriers for protein folding probed by multiple perturbation analysis

The characterization of the free energy barriers has been a major goal in studies on the mechanism of protein folding. Testing the effect of mutations or denaturants on protein folding reactions revealed that transition state movement is rare, suggesting that folding barriers are robust and narrow maxima on the free energy landscape. Here we demonstrate that the application of multiple perturbations allows the observation of small transition state movements that escape detection in single perturbation experiments. We used tendamistat as a model protein to test the broadness of the free energy barriers. Tendamistat folds over two consecutive transition states and through a high-energy intermediate. Measuring the combined effect of temperature and denaturant on the position of the transition state in the wild-type protein and in several mutants revealed that the early transition state shows significant transition state movement. Its accessible surface area state becomes more native-like with destabilization of the native state by temperature. To the same extent, the entropy of the early transition state becomes more native-like with increasing denaturant concentration, in accordance with Hammond behavior. The position of the late transition state, in contrast, is much less sensitive to the applied perturbations. These results suggest that the barriers in protein folding become increasingly narrow as the folding polypeptide chain approaches the native state.     

Cryptic population genetic structure: the number of inferred clusters depends on sample size

Clustering methods have been used extensively to unravel cryptic population genetic structure. We investigated the effect of the number of individuals sampled in each location on the resulting number of clusters. Our study was motivated by recent results in Arabidopsis thaliana: studies in which more than one individual was sampled per location apparently have led to a much higher number of clusters than studies where only one individual was sampled in each location, as is generally done in this species. We show, using computer simulations and microsatellite data in A. thaliana, that the number of sampled individuals indeed has a strong impact on the number of resulting clusters. This effect is smaller if the sampled populations have a hierarchical structure. In most cases, sampling 5–10 individuals per population should be enough. The results argue for abandoning the concept of ‘accessions’ in partially selfing organisms.     

Gibb's free energy as a index of the assimilation of carbohydrate sources by bacteria]

The author presents substantiation of the use of thermodynamic function--of free Gibbs' energy (--deltaG) for energy characteristics of enterobacteria periodic cultures on synthetic media. Examination of strains of E. coli K12P4X Hfr, E. coli PA-309, and Sh. newcastle 762S showed the --detlaG = f (N) curves to characterise the energy value of various carbohydrate sources more completely, and also permitted the choice of their optimal concentrations in synthetic media for each of the enterobacteria strain.     

Continuous metadynamics in essential coordinates as a tool for free energy modelling of conformational changes

Modelling of conformational changes in biopolymers is one of the greatest challenges of molecular biophysics. Metadynamics is a recently introduced free energy modelling technique that enhances sampling of configurational (e.g. conformational) space within a molecular dynamics simulation. This enhancement is achieved by the addition of a history-dependent bias potential, which drives the system from previously visited regions. Discontinuous metadynamics in the space of essential dynamics eigenvectors (collective motions) has been proposed and tested in conformational change modelling. Here, we present an implementation of two continuous formulations of metadynamics in the essential subspace. The method was performed in a modified version of the molecular dynamics package GROMACS. These implementations were tested on conformational changes in cyclohexane, alanine dipeptide (terminally blocked alanine, Ace-Ala-Nme) and SH3 domain. The results illustrate that metadynamics in the space of essential coordinates can accurately model free energy surfaces associated with conformational changes. Figure The conformational free energy surface of cyclohexane in the space of the two most intensive collective motions.

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