Super-grid Linear Eddy Model (SG-LEM): Efficient mode- and regime-independent combustion closure for Large Eddy Simulation (LES)

Next-generation combustion technology such as ‘lean burn’ and HCCI (Homogeneous Charge Compression Ignition) present new challenges for\ua0 combustion modelling. The presence of locally varying combustion modes (premixed vs. non-premixed) and regimes (fast/non-fast chemistry vs.\ua0 turbulent time scales) belie a need for combustion models that make few assumptions of the underlying combustion process and can also incorporate\ua0 turbulent stirring. Lean burn for gas-turbines introduce complex ignition sequences and phenomena like blowout which requires both a finite-rate\ua0 chemistry description as well as turbulence-chemistry-interaction for accurate modelling. Auto- ignition and differential-diffusion capabilities are also\ua0 desirable features for modelling HCCI and hydrogen combustion, respectively. The Linear Eddy Model (LEM) is a mode- and regime- independent sub-grid\ua0 combustion closure for Large Eddy Simulation (LES). LEM resolves, along a one-dimensional line, all spatial and temporal scales, provides on-the-fly\ua0 local turbulent flame statistics, captures finite rate chemistry effects, and directly incorporates turbulence-chemistry interaction using stochastic\ua0 processes. In LES-LEM an LEM-line is advanced in each LES cell which makes the approach computationally rather expensive.In this thesis, a novel closure approach is presented using LEM which involves coarse-graining of the LES mesh to generate a coarse ‘super-grid’\ua0 comprised of ‘super-cells’. Each super-cell, instead of each LES cell, then contains a single LEM line which ad-vances the combined reaction-diffusion equations and also provides binned statistics for thermochemical scalars such as species mass fractions, the method is hence termed ‘super-grid LES- LEM’ or simply, ‘SG-LEM’. Local LES filtered states are then obtained by probability-density-function (PDF) weighted integration of binned scalars, akin to\ua0 standard presumed PDF approaches for reactive LES. The thesis also introduces a new ‘splicing’ scheme for the super-grid formulation where LES\ua0 resolved flow information is accounted for via Lagrangian transport of LEM fragments between adjacent domains. A pressure based solver was developed\ua0 using the OpenFOAM library to test the proposed model with a premixed ethylene flame stabilized over a backward facing step, a setup for which DNS\ua0 data is available for validation. The new model is able to produce LES-resolved flame structures and species mass fractions at a significantly lower cost\ua0 than standard LES-LEM. Comparison with time-averaged reaction rates show good agreement with DNS data where the model is able to correctly capture\ua0 regions of net production and consumption of highly sensitive OH. In general, SG-LEM is able to provide high fidelity reaction rate statistics with\ua0 the compute efficiency of a mapping-type closure. The encouraging results and performance of SG-LEM indicate its suitability for industrial reacting\ua0 simulations once full validation is complete. While it is yet unclear how the presented mapping strategy will cope with transient phenomena like\ua0 extinction, it retains desirable features of LES-LEM and is able to report thermochemical scalars averaged over individual LEM domains for diagnosis

A Survey on Flip Flop Replacement to Latch on Various Design

This paper presents survey for the replacement of flip flop to latches and the advantages of the latch based sequential design Flip flop are the major part of the design a sequential elements and this flip flop has more disadvantages as performance decreases and area increases. An alternate method to increase the performance and reduce the area size latches. Latches are used instead of flip flops in certain places to increase the performance and decrease the area

A Survey on Flip Flop Replacement to Latch on Various Design

This paper presents survey for the replacement of flip flop to latches and the advantages of the latch based sequential design Flip flop are the major part of the design a sequential elements and this flip flop has more disadvantages as performance decreases and area increases. An alternate method to increase the performance and reduce the area size latches. Latches are used instead of flip flops in certain places to increase the performance and decrease the area

Biology of AAV Vectors in the Central Nervous System

Adeno-Associated Viruses (AAV) have emerged as the vector platform of choice for therapeutic gene transfer towards multiple genetic disorders with neurological manifestations. My doctoral thesis was focused on a) evaluating CNS spread, transduction profiles, receptor interactions and clearance; and b) understanding the physiological and biochemical checkpoints governing AAV biologics in the CNS. In our first study, we engineered an AAV4 variant (AAV4.18) that shows expanded tropism from ependymal cells to migrating progenitors in the developing brain. AAV4.18 revealed a striking shift in glycan engagement from 2,3-linked Sialic acid (SA) to 2,8-linked Polysialic acid (PSA). PSA is an important biomarker of neurogenesis. We also report opposing roles of SA and PSA on CNS transduction of AAV4. Overall, carbohydrate content can be exploited to regulate viral tropism in the brain. We then evaluated a lab-derived chimeric AAV2g9, developed through rational vector design. Direct brain injections of AAV2g9 resulted in widespread neuronal transduction with reduced glial tropism. As compared to AAV9, AAV2g9 displayed minimal systemic leakage and off-target gene expression within peripheral organs. We utilized AAV2g9 for brain-specific deletion of ubiquitously expressed MIR137 schizophrenia risk gene using CRISPR/Cas9 technology. Our approach exemplifies control over AAV tropism at both cellular and organ levels to potentially improve vector safety. Lastly, AAV mediated CNS gene therapy requires a deeper understanding of factors affecting transduction efficiency and clearance. Dysfunction in aquaporin-4 (AQP4) mediated CSF flux during aging or disease is correlated with ineffective solute clearance from the brain. Aged mice showed mislocalized AQP4 expression and increased AAV9 deposition following intraCSF administration. We further compared wildtype (WT) and AQP4 knockout (AQP4-/-) mouse CNS. Minutes after intraCSF administration, AQP4-/- mice exhibited highly restricted spread of fluorophore labeled AAV9. Transgene expression was markedly increased 2 weeks post AAV9 administrations in AQP4-/- mice. Further, AQP4-/- mice showed markedly reduced AAV biodistribution and transgene expression in peripheral organs. This suggests that AQP4-deregulation affects CNS spread, transduction efficiency and systemic leakage of AAV vectors. We hypothesize that altered CSF flux under conditions of aging, CNS disease or injury can impact AAV residence time and gene transfer efficiency.Doctor of Philosoph

DNAV: A WebGL Based Tool for Visualizing the Twists and Turns in the Human Genome

The human genome is tightly folded to fit within the restricted space of the nucleus. One of the key goals in understanding the folding principles of DNA is to unravel the mysteries of how functional elements that are separated from each other are brought together. Long-range interactions between folded segments of chromosomes form complex three-dimensional networks and are fundamental in controlling gene expression. These long-range interactions have been observed using chromosome conformation capture (3C). This Hi-C data contains a wealth of information on the nearest-neighbor influence on the deviation of the DNA axis that can be modeled theoretically. We have developed a tool using WebGL to visualize the modeled structures

Differential binding of RNA polymerase to the wild type Mu mom promoter and its C independent mutant: a theoretical analysis

Using the theoretical model for DNA bending we have analyzed the Mu mom promoter wild type and its mutant tin7 which showed differential binding to the RNA polymerase. We have demonstrated here the structural change as a result of the point mutation which may be responsible for the altered binding of RNA polymerase. Analysis using both sets of parameters essentially gives the same result

Pressure Coupling Of the Spherical Linear Eddy Model to RANS-CFD for Internal-Combustion Engine Simulation

As a result of the increase of the use of combustion engines, more restrictive emission standards are applied. New combustion technologies are being constantly developed to enhance the internal combustion engine, this is motivated by overcoming issues that are relevant for both engine efficiency and the environmental aspects. To do that, turbulent combustion modelling is needed.In this paper, an updated version of the Linear Eddy Model (LEM) will be presented. LEM is capable of simulating premixed, non- premixed and mixed mode combustion, and it is a regime independent model that runs under the assumption of finite-rate chemistry that is sensitive to turbulent chemistry interactions, which makes it suitable for prediction of pollutant formation. A New coupling scheme to the CFD-RANS simulation is proposed, the coupling is based on linking the two models via pressure. The benefits of pressure coupling are that the effects of wall heat losses and latent heat of evaporation that are modelled on the CFD side are an intrinsic part of the pressure term that is linking the two models, in contrast to volume coupling in which these relevant phenomena need supplementary modelling on the LEM side. The pressure coupling results in a radially uniform dilatation of the LEM domain reflecting the combined effects of pressure change, fuel addition, and cylinder volume change during the engine cycle. Consistency of the LEM cone volume and the CFD domain volume is maintained by adopting a split operator strategy involving a volume correction that adjusts the cone angle.A Spherical Stand-Alone Linear Eddy Model (SSALEM) has been created to conduct relatively fast simplified code development and parameter studies. SSALEM input parameters were drawn from a WSR-RANS simulation and a 1D slider-crank model that calculates the combustion chamber volume that corresponds to a given crank-angle. Model results show the capability to physically track the evolution of several scalars that are solved on the LEM line such as temperature, fuel, and intermediate species in the combustion process

Application of artificial neural networks for prokaryotic transcription terminator prediction

Artificial neural networks (ANN) to predict terminator sequences, based on a feed-forward architecture and trained using the error back propagation technique, have been developed. The network uses two different methods for coding nucleotide sequences. In one the nucleotide bases are coded in binary while the other uses the electron-ion interaction potential values (EIIP) of the nucleotide bases. The latter strategy is new, property based and substantially reduces the network size. The prediction capacity of the artificial neural network using both coding strategies is more than 95%

Lodging in soybean (Glycine max) as influenced by growth habit and other traits

Thirty soybean varieties were grown for consecutive two years to study how the growth habit, stem diameter and plant height influence the lodging in soybean. Plant height was found to be significant and positively correlated with lodging and growth habit. The reduced plant height showed increased resistance to lodging in soybean. Growth habit was significantly correlated with plant height, nodes and lodging. Stem diameter was not significant with any of the traits studied. Although the determinate varieties were shorter, equivalent yields were produced by determinate and semi-determinate. No significant correlation was established between growth habit and yield; however, JS 95-60 was the highest yielder followed by JS 335, RKS 18, JS 93-05, MAUS 71, NRC 37 and PS 1225. Semi-determinate varieties were comparatively taller than determinates and susceptible for lodging

Biology of adeno-associated viral vectors in the central nervous system

Gene therapy is a promising approach for treating a spectrum of neurological and neurodegenerative disorders by delivering corrective genes to the central nervous system (CNS). In particular, adeno-associated viruses (AAVs) have emerged as promising tools for clinical gene transfer in a broad range of genetic disorders with neurological manifestations. In the current review, we have attempted to bridge our understanding of the biology of different AAV strains with their transduction profiles, cellular tropisms, and transport mechanisms within the CNS. Continued efforts to dissect AAV-host interactions within the brain are likely to aid in the development of improved vectors for CNS-directed gene transfer applications in the clinic