Temporal changes of mechanical signals and extracellular composition in human intervertebral disc during degenerative progression

In this study, a three-dimensional finite element model was used to investigate the changes in tissue composition and mechanical signals within human lumbar intervertebral disc during the degenerative progression. This model was developed based on the cell-activity coupled mechano-electrochemical mixture theory. The disc degeneration was simulated by lowering nutrition levels at disc boundaries, and the temporal and spatial distributions of the fixed charge density, water content, fluid pressure, Von Mises stress, and disc deformation were analyzed. Results showed that fixed charge density, fluid pressure, and water content decreased significantly in the nucleus pulposus (NP) and the inner to middle annulus fibrosus (AF) regions of the degenerative disc. It was found that, with degenerative progression, the Von Mises stress (relative to that at healthy state) increased within the disc, with a larger increase in the outer AF region. Both the disc volume and height decreased with the degenerative progression. The predicted results of fluid pressure change in the NP were consistent with experimental findings in the literature. The knowledge of the variations of temporal and spatial distributions of composition and mechanical signals within the human IVDs provide a better understanding of the progression of disc degeneration.     

The control structure of the nematode Caenorhabditis elegans: Neuro-sensory integration and proprioceptive feedback

We develop a biophysically realistic model of the nematode C. elegans that includes: (i) its muscle structure and activation, (ii) key connectomic activation circuitry, and (iii) a weighted and time-dynamic proprioception. In combination, we show that these model components can reproduce the complex waveforms exhibited in C. elegans locomotive behaviors, chiefly omega turns. This is achieved via weighted, time-dependent suppression of the proprioceptive signal. Though speculative, such dynamics are biologically plausible due to the presence of neuromodulators which have recently been experimentally implicated in the escape response, which includes an omega turn. This is the first integrated neuromechanical model to reveal a mechanism capable of generating the complex waveforms observed in the behavior of C. elegans, thus contributing to a mathematical framework for understanding how control decisions can be executed at the connectome level in order to produce the full repertoire of observed behaviors.     

Modeling the formation of root apices

The formation of new root apices from small groups of cells with different cellular patterns has been simulated using an existing model based on growth tensors. To generate an apex, a steady growth field was used. The pattern of cells evolved to approach the steady state. Two extreme types of progressions have been obtained : one leading to an apex with a single or a few apical cells, and the other to an apex with a quiescent centre. The change of structure while applying a steady growth tensor indicates that development may involve a succession of discrete growth tensors.     

Modeling the two-dimensional accuracy of soccer kicks

In many sports, athletes perform motor tasks that simultaneously require both speed and accuracy for success, such as kicking a ball. Because of the biomechanical trade-off between speed and accuracy, athletes must balance these competing demands. Modelling the optimal compromise between speed and accuracy requires one to quantify how task speed affects the dispersion around a target, a level of experimental detail not previously addressed. Using soccer penalties as a system, we measured two-dimensional kicking error over a range of speeds, target heights, and kicking techniques. Twenty experienced soccer players executed a total of 8466 kicks at two targets (high and low). Players kicked with the side of their foot or the instep at ball speeds ranging from 40% to 100% of their maximum. The inaccuracy of kicks was measured in horizontal and vertical dimensions. For both horizontal and vertical inaccuracy, variance increased as a power function of speed, whose parameter values depended on the combination of kicking technique and target height. Kicking precision was greater when aiming at a low target compared to a high target. Side-foot kicks were more accurate than instep kicks. The centre of the dispersion of shots shifted as a function of speed. An analysis of the covariance between horizontal and vertical error revealed right-footed kickers tended to miss below and to the left of the target or above and to the right, while left-footed kickers tended along the reflected axis. Our analysis provides relationships needed to model the optimal strategy for penalty kickers.     

Alternation of DNA and Solvent Layers in the A Form of d(GGCGCC) Obtainhted by Ethanol Crystallization

Abstract

We have determined by X-ray crystallography the structure of the hexamer duplex d(GGCGCC)₂ in the A-form using ethanol as a precipitant. The same sequence had previously been crystallized in the B-form, but with 2-methyl-2, 4-pentanediol as a precipitant. It appears that ethanol precipitation is a useful method to induce the formation of A-form crystals of DNA. Packing of the molecules in the crystal has unique features: the known interaction of A-DNA duplexes between terminal base-pairs and the minor groove of neighbor molecules is combined with a superstructure consisting in an alternation of DNA layers and solvent layers (water/ions). This organization in layers has been observed before, also with hexamers in the A conformation which crystallize in the same space group (C222 ₁). The solvent layer has a precise thickness, although very few ordered water molecules can be detected. Another feature of this crystal is its large unit cell, which gives rise to an asymmetric unit with three hexamer duplexes. One of the three duplexes is quite different from the other two in several aspects: the number of base pairs per turn, the twist pattern, the mean value of the twist angle and the fact that one terminal base-pair is not stacked as part of the duplex and appears to be disordered. So the variability in conformation of this sequence is remarkable.     

Balancing the Ethanol Formation in Continuous Bioreactors with Ethanol Stripping

Ethanol microbially produced in continuously operated aerated bioreactors is partly discharged with the liquid flow and is partly stripped off with the gas phase. The calculation of ethanol formation rates – as required, for example, in data evaluation by Metabolic Flux Analysis – solely based on the liquid‐borne ethanol, while neglecting the ethanol stripping, inevitably results in defective data interpretation. The proportion of stripped ethanol can be measured or, alternatively, calculated. The developed structured model describes the ethanol stripping as a two‐step process while differentiating between the phase transition from the liquid into the gas and the discharge of the evaporated ethanol with the off‐gas. As shown by model analysis as well as stripping experiments, the stripping rate is mainly determined by the ethanol discharge rather than by the phase transition. Consequently, the ethanol‐stripping rate depends on the specific gas flow rate and the partition coefficient for ethanol (at 30 °C, K_L/G = 3125 L/L), but not on the mass transfer coefficient. As shown by model simulations, the lower the dilution rate and the larger the gas flow rate of an aerated chemostat with a microbial ethanol formation, the higher the proportion of stripped ethanol. Under practically relevant conditions, more than 30 % of the produced ethanol may be stripped off. Exhaust‐gas coolers, actually used to reduce water losses by evaporation, do not prevent but slightly affect ethanol stripping.     

Inhibitory factors affecting the process of enhanced biological phosphorus removal (EBPR) – A mini-review

Enhanced biological phosphorus removal (EBPR) technology has been widely considered as a key strategy in preventing eutrophication and recognized as the advancing front of research in wastewater treatment. The key to keep its high efficiency in biological phosphorus removal is to optimize the operation and management of the system. Previous research in this field has undoubtedly improved understanding of the factors hindered overall efficiency of EBPR. However, it is obvious that much remains to be learnt. This paper attempts to review the fundamental understanding in factors inhibiting the stability and reliability of the EBPR systems in the state-of-the-art research. In view of modeling the EBPR systems, an appropriate extension of the current mechanistic models with these inhibitory factors is recommended in order to better simulate and predict the behavior of full-scale and lab-scale EBPR plants. From the perspectives of the further mechanistic and multi-factors study, the direction of denitrifying dephosphatation and granules/biofilms are also discussed. This comprehensive overview will not only help us to understand the overall mechanism of the EBPR process, but also benefit the researchers and engineers to consider all the possible factors affecting the process in the urban sewage treatment plants.     

Two Algorithms for Defining Atoms and Molecules in Condensed Phases

Abstract

Two algorithms for defining single entities in condensed phase based on the calculation of a zero flux surface of the gradient of the electron density are proposed. First the two approaches are applied to a water molecule in a liquid system; the different behaviour of the two algorithms is graphically shown in the planar section of the molecular plane (i.c., HOH plane of the molecule analyzed). Next, using the two algorithms for partitioning electron density, the average molecular dipole moment of the water molecule in liquid phase is calculated averaging over several configurations; analogies and differences with other methods are reported and their physical interpretation is discussed. There exist different approaches for calculating the zero flux surface (or equivalently the volume defined by such a surface); the two described in this work differ from the others because the calculation in both cases is straightforward (i.e., the surface is determined directly from the data corresponding to the electron density) and is characterized by a relatively short computational time.     

Functional Identification of the Hypoxanthine/Guanine Transporters YjcD and YgfQ and the Adenine Transporters PurP and YicO of Escherichia coli K-12

The evolutionarily broad family nucleobase-cation symporter-2 (NCS2) encompasses transporters that are conserved in binding site architecture but diverse in substrate selectivity. Putative purine transporters of this family fall into one of two homology clusters: COG2233, represented by well studied xanthine and/or uric acid permeases, and COG2252, consisting of transporters for adenine, guanine, and/or hypoxanthine that remain unknown with respect to structure-function relationships. We analyzed the COG2252 genes of Escherichia coli K-12 with homology modeling, functional overexpression, and mutagenesis and showed that they encode high affinity permeases for the uptake of adenine (PurP and YicO) or guanine and hypoxanthine (YjcD and YgfQ). The two pairs of paralogs differ clearly in their substrate and ligand preferences. Of 25 putative inhibitors tested, PurP and YicO recognize with low micromolar affinity N⁶-benzoyladenine, 2,6-diaminopurine, and purine, whereas YjcD and YgfQ recognize 1-methylguanine, 8-azaguanine, 6-thioguanine, and 6-mercaptopurine and do not recognize any of the PurP ligands. Furthermore, the permeases PurP and YjcD were subjected to site-directed mutagenesis at highly conserved sites of transmembrane segments 1, 3, 8, 9, and 10, which have been studied also in COG2233 homologs. Residues irreplaceable for uptake activity or crucial for substrate selectivity were found at positions occupied by similar role amino acids in the Escherichia coli xanthine- and uric acid-transporting homologs (XanQ and UacT, respectively) and predicted to be at or around the binding site. Our results support the contention that the distantly related transporters of COG2233 and COG2252 use topologically similar side chain determinants to dictate their function and the distinct purine selectivity profiles.     

Process Development in Biotechnology – A Re‐Evaluation

This review considers some process development problems in biotechnology and presents examples of solutions, which were developed in cooperation with industrial partners. These processes include the production of restriction endonuclease EcoRI by recombinant Escherichia coli, which is toxic to the cell, penicillin V by Penicillium chrysogenum, xylanase by Aspergillus awamori, cephalosporin C by Acremonium chrysogenum, erythritol by Moniliella tomentosa var pollinis, and alkaline serine protease by Bacillus licheniformis. Special attention is given to the practical aspects of product development.