SUPPORTING ENVIRONMENTALLY-BENIGN DESIGN ELUCIDATING ENVIRONMENTAL IMPACT PROPAGATION IN CONCEPTUAL DESIGN PHASE BY SAPPHIRE MODEL OF CAUSALITY

Conceptual Design Phase is the most critical for design decisions and their impact on the Environment. It is also a phase of many `unknowns' making it flexible and allowing exploration of many solutions. Thus, it is a challenge to determine the most Environmentally-benign Solution or Concept to be translated in to a `good' product. The SAPPhIRE Model captures the various levels of abstractions present in Conceptual Design by Outcomes and defines a Solution-variant as a set of verifiable and quantifiable Outcomes. The Causality explains the propagation of Environmental Impact across Outcomes at varying levels of abstraction, suggesting that the Environmental Impact of an Outcome at a certain level can be represented as a collation of Environmental Impact information of all the Outcomes at each of its subsequent lower levels of abstraction. Thus a ball-park impact value can be associated with the higher-levels of abstraction, thereby supporting design decisions taken earlier on in Conceptual Design directing towards Environmentally-benign Design.

Differential proteomic and genomic profiling of mouse striatal cell model of Huntington's disease and control; probable implications to the disease biology

Huntington's disease (HD) is an autosomal dominant disorder of central nervous system caused by expansion of CAG repeats in exon1 of the huntingtin gene (Htt). Among various dysfunctions originated from the mutation in Htt gene, transcriptional deregulation has been considered to be one of the most important abnormalities. Large numbers of investigations identified altered expressions of genes in brains of HD patients and many models of HD. In this study we employed 2D SDS-PAGE/MALDI-MS coupled with 2D-DIGE and real-time PCR experiments of an array of genes focused to HD pathway to determine altered protein and gene expressions in STHdh(Q111)/Hdh(Q111) cells, a cell model of HD and compared with STHdh(Q7)/Hdh(Q7) cells, its wild type counterpart. We annotated 76 proteins from these cells and observed differential expressions of 31 proteins (by 2D-DIGE) involved in processes like unfolded protein binding, negative regulation of neuron apoptosis, response to superoxides etc. Our PCR array experiments identified altered expressions of 47 genes. Altogether significant alteration of 77 genes/proteins could be identified in this HD cell line with potential relevance to HD biology. Biological significance: In this study we intended to find out differential proteomic and genomic profiles in HD condition. We used the STHdh cells, a cellular model for HD and control. These are mouse striatal neuronal cell lines harboring 7 and 111 knock -in CAG repeats in their two alleles. The 111Q containing cell line (STHdh(Q111)/Hdh(Q111)) mimics diseased condition, whereas the 7Q containing ones (STHdh(Q7)/Hdh(Q7)), serves as the proper control cell line. Proteomic experiments were performed earlier to obtain differential expressions of proteins in R6/2 mice models, Hdh(Q) knock -in mice and in plasma and CSF from HD patients. However, no earlier report on proteomic alterations in these two HD cell lines and control was available in literature. It was, therefore, an important objective to find out differential expressions of proteins in these two cell lines. In this study, we annotated 76 proteins from STHdh(Q7)/Hdh(Q7) and STHdh(Q111)/Hdh(Q111) cells using 2D-gel/mass spectrometry. Next, by performing 2D-DIGE, we observed differential expressions of 31 proteins (16 upregulated and 15 downregulated) between these two cell lines. We also performed customized qRT-PCR array focused to HD pathway and found differential expressions of 47 genes (8 gene exptessions increased and 39 genes were decreased significantly). A total of 77 genes/proteins (Htt downregulated in both the studies) were found to be significantly altered from both the experimental paradigms. We validated the differential expressions of Vim, Hypk, Ran, Dstn, Hspa5 and Sod2 either by qRT-PCR or Western blot analysis or both. Out of these 77, similar trends in alteration of 19 out of 31 and 38 out of 47 proteins/genes were reported in earlier studies. Thus our study confirmed earlier observations on differential gene/protein expressions in HD and are really useful. Additionally, we observed differential expression of some novel genes/proteins. One of this was Hypk, a Htt-interacting chaperone protein with the ability to solubilize mHtt aggregated structures in cell lines. We propose that downregulation of Hypk in STHdh-Qm (Q111)/Hdh(Q111) has a causal effect towards HD pathogenesis. Thus the novel findings from our study need further research and might be helpful to understand the molecular mechanism behind HD pathogenesis. (C) 2015 Elsevier B.V. All rights reserved.

Physiological role of FolD (methylenetetrahydrofolate dehydrogenase), FchA (methenyltetrahydrofolate cyclohydrolase) and Fhs (formyltetrahydrofolate synthetase) from Clostridium perfringens in a heterologous model of Escherichia coli

Most organisms possess bifunctional FolD 5,10-methylenetetrahydrofolate (5,10-CH2-THF) dehydrogenase-cyclohydrolase] to generate NADPH and 10-formyltetrandrofolate (10-CHO-THF) required in various metabolic steps. In addition, some organisms including Clostridium perfringens possess another protein, Fhs (formyltetrahydrofolate synthetase), to synthesize 10-CHO-THF. Here, we show that unlike the bifunctional FolD of Escherichia coli (Eco FolD), and contrary to its annotated bifunctional nature, C. perfringens FolD (Cpe FoID) is a monofunctional 5,10-CH2-THF dehydrogenase. The dehydrogenase activity of Cpe FoID is about five times more efficient than that of Eco FolD. The 5,10-methenyltetrahydrofolate (5,10-CH+-THF) cyclohydrolase activity in C. perfringens is provided by another protein, FchA (5,10-CH+-THF cyclohydrolase), whose cyclohydrolase activity is similar to 10 times more efficient than that of Eco FolD. Kinetic parameters for Cpe Fhs were also determined for utilization of all of its substrates. Both Cpe FoID and Cpe FchA are required to substitute for the single bifunctional FolD in E. coli. The simultaneous presence of Cpe FoID and Cpe FchA is also necessary to rescue an E coli folD deletion strain (harbouring Cpe Fhs support) for its formate and glycine auxotrophies, and to alleviate its susceptibility to trimethoprim (an antifolate drug) or UV light. The presence of the three clostridial proteins (FolD, FchA and Fhs) is required to maintain folate homeostasis in the cell.

Peierls-Nabarro model of interfacial misfit dislocation: An analytic solution

We propose a method to treat the interfacial misfit dislocation array following the original Peierls-Nabarro's ideas. A simple and exact analytic solution is derived in the extended Peierls-Nabarro's model, and this solution reflects the core structure and the energy of misfit dislocation, which depend on misfit and bond strength. We also find that only with beta < 0.2 the structure of interface can be represented by an array of singular Volterra dislocations, which conforms to those of atomic simulation. Interfacial energy and adhesive work can be estimated by inputting ab initio calculation data into the model, and this shows the method can provide a correlation between the ab initio calculations and elastic continuum theory.

The modified Peierls-Nabarro model of interfacial misfit dislocation

The Peierls-Nabarro model of the interfacial misfit dislocation array is analytically extended to a family of dislocations of greater widths. By adjusting a parameter, the width of the misfit dislocations, the distribution of the shear stress, and the restoring force law can be systematically varied. The smaller the amplitude of the restoring force, the wider the misfit dislocations and the lower the interfacial energy.

Analysis of strip electric saturation model of crack problem in piezoelectric materials

This paper presents a fully anisotropic analysis of strip electric saturation model proposed by Gao et al. (1997) (Gao, H.J., Zhang, T.Y., Tong, P., 1997. Local and global energy release rates for an electrically yielded crack in a piezoelectric ceramic. J. Mech. Phys. Solids, 45, 491-510) for piezoelectric materials. The relationship between the size of the strip saturation zone ahead of a crack tip and the applied electric displacement field is established. It is revealed that the critical fracture stresses for a crack perpendicular to the poling axis is linearly decreased with the increase of the positive applied electric field and increases linearly with the increase of the negative applied electric field. For a crack parallel to the poring axis, the failure stress is not effected by the parallel applied electric field. In order to analyse the existed experimental results, the stress fields ahead of the tip of an elliptic notch in an infinite piezoelectric solid are calculated. The critical maximum stress criterion is adopted for determining the fracture stresses under different remote electric displacement fields. The present analysis indicates that the crack initiation and propagation from the tip of a sharp elliptic notch could be aided or impeded by an electric displacement field depending on the field direction. The fracture stress predicted by the present analysis is consistent with the experimental data given by Park and Sun (1995) (Park, S., Sun, C.T., 1995. Fracture criteria for piezoelectric materials. J. Am. Ceram. Soc 78, 1475-1480).

Numerical Analysis of Theoretical Model of the Rf MEMs Switches

An improved electromechanical model of the RF MEMS (radio frequency microelectromechanical systems) switches is introduced, in which the effects of intrinsic residual stress from fabrication processes, axial stress due to stretching of beam, and fringing field are taken into account. Four dimensionless numbers are derived from the governing equation of the developed model. A semi-analytical method is developed to calculate the behavior of the RF MEMS switches. Subsequently the influence of the material and geometry parameters on the behavior of the structure is analyzed and compared, and the corresponding analysis with the dimensionless numbers is conducted too. The quantitative relationship between the presented parameters and the critical pull-in voltage is obtained, and the relative importance of those parameters is given.

The Displacement and Strain Field of Three-Dimensional Rheologic Model of Earthquake Preparation

Based on the three-dimensional elastic inclusion model proposed by Dobrovolskii, we developed a rheological inclusion model to study earthquake preparation processes. By using the Corresponding Principle in the theory of rheologic mechanics, we derived the analytic expressions of viscoelastic displacement U(r, t) , V(r, t) and W(r, t), normal strains epsilon(xx) (r, t), epsilon(yy) (r, t) and epsilon(zz) (r, t) and the bulk strain theta (r, t) at an arbitrary point (x, y, z) in three directions of X axis, Y axis and Z axis produced by a three-dimensional inclusion in the semi-infinite rheologic medium defined by the standard linear rheologic model. Subsequent to the spatial-temporal variation of bulk strain being computed on the ground produced by such a spherical rheologic inclusion, interesting results are obtained, suggesting that the bulk strain produced by a hard inclusion change with time according to three stages (alpha, beta, gamma) with different characteristics, similar to that of geodetic deformation observations, but different with the results of a soft inclusion. These theoretical results can be used to explain the characteristics of spatial-temporal evolution, patterns, quadrant-distribution of earthquake precursors, the changeability, spontaneity and complexity of short-term and imminent-term precursors. It offers a theoretical base to build physical models for earthquake precursors and to predict the earthquakes.

A Numerical Model of Rapid Solidification Processing of Ni-Al Alloy in Planar Flow Casting

A numerical model has been developed for simulating the rapid solidification processing (RSP) of Ni-Al alloy in order to predict the resultant phase composition semi-quantitatively during RSP. The present model couples the initial nucleation temperature evaluating method based on the time dependent nucleation theory, and solidified volume fraction calculation model based on the kinetics model of dendrite growth in undercooled melt. This model has been applied to predict the cooling curve and the volume fraction of solidified phases of Ni-Al alloy in planar flow casting. The numerical results agree with the experimental results semi-quantitatively.

Modified Simplified Rate Equation Model of Flowing Chemical Oxygen-Iodine Laser and its Application

A modified simplified rate equation (RE) model of flowing chemical oxygen-iodine laser (COIL), which is adapted to both the condition of homogeneous broadening and inhomogeneous broadening being of importance and the condition of inhomogeneous broadening being predominant, is presented for performance analyses of a COIL. By using the Voigt profile function and the gain-equal-loss approximation, a gain expression has been deduced from the rate equations of upper and lower level laser species. This gain expression is adapted to the conditions of very low gas pressure up to quite high pressure and can deal with the condition of lasing frequency being not equal to the central one of spectral profile. The expressions of output power and extraction efficiency in a flowing COIL can be obtained by solving the coupling equations of the deduced gain expression and the energy equation which expresses the complete transformation of the energy stored in singlet delta state oxygen into laser energy. By using these expressions, the RotoCOIL experiment is simulated, and obtained results agree well with experiment data. Effects of various adjustable parameters on the performances of COIL are also presented.

Electromechanical Model of RF MEMS Switches

With the recent rapid growth of Radio Frequency Micro-Electro-Mechanical Systems (RF MEMS) switches, there has developed an emergent requirement for more accurate theoretical models to predict their electromechanical behaviors. Many parameters exist in the analysis of the behavior of the switch, and it is inconvenient for further study. In this paper, an improved model is introduced, considering simultaneously axial stress, residual stress, and fringing-field effect of the fixed-fixed bridge structure. To avoid any unnecessary repetitive model tests and numerical simulation for RF MEMS switches, some dimensionless numbers are derived by making governing equation dimensionless. The electromechanical behavior of the fixed-fixed bridge structure of RF MEMS switches is totally determined by these dimensionless numbers.

Unsteady Model of Drop Marangoni Migration in Microgravity

The experiments of drop Marangoni migration have been performed by the drop shift facility of short period of 4.5 s, and the drop accelerates gradually to an asymptotic velocity during the free fall. The unsteady and axisymmetric model is developed to study the drop migration for the case of moderate Reynolds number Re = O(1), and the results are compared with the experimental ones in the present paper. Both numerical and experimental results show that the migration velocity for moderate Reynolds number is several times smaller than that given by the linear YGB theory.

A simulation model of a floating half zone

A simulation model of a floating half zone was suggested by steady numerical simulation and experiment respectively, in the previous papers [Q.S. Chen, W.R. Hu, Int. J. Mass Heat Transfer 40 (1997) 757; J.H. Han, Y. Ar, R. Zhou, W.R. Hue, Int. J. Mass Heat Transfer 40 (1997) 2671]. In the present paper, the simulation model is studied by using the method of unsteady and three-dimensional numerical simulation, and the transient process from steady convection to oscillatory convection is especially analyzed. Comparison of onsets of oscillation for both simulation model and the usual model were obtained, and the results show that the critical Marangoni number of the simulation model is obviously smaller than that of the usual model for the same slender liquid bridge. This implies that the usual model of a floating half zone gives a lower estimation on the onset of oscillation for floating zone convection.

Evolution induced catastrophe in a nonlinear dynamical model of material failure

In order to study the failure of disordered materials, the ensemble evolution of a nonlinear chain model was examined by using a stochastic slice sampling method. The following results were obtained. (1) Sample-specific behavior, i.e. evolutions are different from sample to sample in some cases under the same macroscopic conditions, is observed for various load-sharing rules except in the globally mean field theory. The evolution according to the cluster load-sharing rule, which reflects the interaction between broken clusters, cannot be predicted by a simple criterion from the initial damage pattern and even then is most complicated. (2) A binary failure probability, its transitional region, where globally stable (GS) modes and evolution-induced catastrophic (EIC) modes coexist, and the corresponding scaling laws are fundamental to the failure. There is a sensitive zone in the vicinity of the boundary between the GS and EIC regions in phase space, where a slight stochastic increment in damage can trigger a radical transition from GS to EIC. (3) The distribution of strength is obtained from the binary failure probability. This, like sample-specificity, originates from a trans-scale sensitivity linking meso-scopic and macroscopic phenomena. (4) Strong fluctuations in stress distribution different from that of GS modes may be assumed as a precursor of evolution-induced catastrophe (EIC).