An exPADItion for citrullination in the developing hair follicle

During epidermal development, to assure proper tissue structure, highly complex transcriptional networks interact within the stem cell compartments of the epidermis and hair follicles (HFs) to balance the choice between self-renewal or differentiation. The full characterisation of the protein profiles resulting from those transcriptional networks, within the compartments of the HF, remains, however, incomplete. Moreover, the proteins themselves can be regulated via posttranslational modification (PTMs). One such PTM is citrullination, carried out by the peptidylarginine deiminase (PADI) family of enzymes. Although, PADIs have been described in other stem and progenitor cells, their role in hair follicle stem cell (HFSC) and progenitor lineages have remained elusive. The main objectives of this thesis are to address the functional consequences of PADI expression in HFSCs during development. Paper I identifies Padi4 expression in the developing HF, where it is found to participate in restricting proliferation and lineage commitment of HF progenitors, as well as playing a role in the central mechanism for translational control, and by doing so altering the distinct sequential events that mark HF differentiation progression. As a result, we identify citrullination as a means to assert regulation of protein function in HFSCs and progenitors. Paper II identifies alternative isoforms of PADI2 and PADI3, in oligodendrocytes and HF differentiated cells, respectively, and show that the alternative isoforms have an incumbering effect on the enzymatic activity and stability of their conventional counterparts. Paper III is a review paper in which meta-analysis of published human citrullinomes in health and inflammatory disease reveals that citrullination is a commonplace yet highly dynamic molecular regulator of protein function. A strong case is made for the involvement of PADIs and citrullination in hair follicle stem cell biology and inflammatory alopecia. Paper IV addresses the involvement of transcription factor ID1 in self-renewal and differentiation of epidermal progenitor cells during development. This study describes how ID1 facilitates synchronisation of progenitor proliferation and differentiation via TCF3- binding, and establishes a novel axis of coordination for how BMP-induction of Id1 expression via pSMAD1/5 is supressed by CEBPa. The combined efforts within this thesis demonstrate the clear and overarching importance of PADIs and citrullination in skin developmental physiology

Optimization of the linear quadratic regulator (LQR) control quarter car suspension system using genetic algorithm

In this paper, a genetic algorithm (GA) based in an optimization approach is presented in order to search the optimum weighting matrix parameters of a linear quadratic regulator (LQR). A Macpherson strut quarter car suspension system is implemented for ride control application. Initially, the GA is implemented with the objective of minimizing root mean square (RMS) controller force. For single objective optimization, RMS controller force is reduced by 20.42% with slight increase in RMS sprung mass acceleration. Trade-off is observed between controller force and sprung mass acceleration. Further, an analysis is extended to multi-objective optimization with objectives such as minimization of RMS controller force and RMS sprung mass acceleration and minimization of RMS controller force, RMS sprung mass acceleration and suspension space deflection. For multi-objective optimization, Pareto-front gives flexibility in order to choose the optimum solution as per designer’s need

Artificial neural network predication and validation of optimum suspension parameters of a passive suspension system

This paper presents the modeling and optimization of quarter car suspension system using Macpherson strut. A mathematical model of quarter car is developed, simulated and optimized in Matlab/Simulink® environment. The results are validated using test rig. The suspension system parameters are optimized using a genetic algorithm for objective functions viz. vibration dose value (VDV), frequency weighted root mean square acceleration (hereafter called as RMS acceleration), maximum transient vibration value, root mean square suspension space and root mean square tyre deflection. ISO 2631-1 standard is adopted to assess ride and health criterion. Results shows that optimum parameters provide ride comfort and health criterions over classical design. The optimization results are experimentally validated using quarter car test setup. The genetic algorithm optimization results are further extended to the artificial neural network simulation and prediction model. Artificial neural network model is carried out in Matlab/Simulink® environment and Neuro Dimensions. Simulation, experimental and predicted results are in close correlation. The optimized system reduces the values of VDV by 45%. Also, RMS acceleration is reduced by 47%. Thus, the optimized system improved ride comfort by reducing RMS acceleration and improved health criterion by reducing the VDV. Finally ANN can be used for predicting the optimum suspension parameters values with good agreement

Intelligent systems for volumetric feature recognition from CAD mesh models

This paper presents an intelligent technique to recognise the volumetric features from CAD mesh models based on hybrid mesh segmentation. The hybrid approach is an intelligent blending of facet-based, vertex based, rule-based, and artificial neural network (ANN)-based techniques. Comparing with existing state-of-the-art approaches, the proposed approach does not depend on attributes like curvature, minimum feature dimension, number of clusters, number of cutting planes, the orientation of model and thickness of the slice to extract volumetric features. ANN-based intelligent threshold prediction makes hybrid mesh segmentation automatic. The proposed technique automatically extracts volumetric features like blends and intersecting holes along with their geometric parameters. The proposed approach has been extensively tested on various benchmark test cases. The proposed approach outperforms the existing techniques favourably and found to be robust and consistent with coverage of more than 95% in addressing volumetric features

Optimization of the linear quadratic regulator (LQR) control quarter car suspension system using genetic algorithm

In this paper, a genetic algorithm (GA) based in an optimization approach is presented in order to search the optimum weighting matrix parameters of a linear quadratic regulator (LQR). A Macpherson strut quarter car suspension system is implemented for ride control application. Initially, the GA is implemented with the objective of minimizing root mean square (RMS) controller force. For single objective optimization, RMS controller force is reduced by 20.42% with slight increase in RMS sprung mass acceleration. Trade-off is observed between controller force and sprung mass acceleration. Further, an analysis is extended to multi-objective optimization with objectives such as minimization of RMS controller force and RMS sprung mass acceleration and minimization of RMS controller force, RMS sprung mass acceleration and suspension space deflection. For multi-objective optimization, Pareto-front gives flexibility in order to choose the optimum solution as per designer’s need

Optimization of the linear quadratic regulator (LQR) control quarter car suspension system using genetic algorithm

In this paper, a genetic algorithm (GA) based in an optimization approach is presented in order to search the optimum weighting matrix parameters of a linear quadratic regulator (LQR). A Macpherson strut quarter car suspension system is implemented for ride control application. Initially, the GA is implemented with the objective of minimizing root mean square (RMS) controller force. For single objective optimization, RMS controller force is reduced by 20.42% with slight increase in RMS sprung mass acceleration. Trade-off is observed between controller force and sprung mass acceleration. Further, an analysis is extended to multi-objective optimization with objectives such as minimization of RMS controller force and RMS sprung mass acceleration and minimization of RMS controller force, RMS sprung mass acceleration and suspension space deflection. For multi-objective optimization, Pareto-front gives flexibility in order to choose the optimum solution as per designer’s need

Optimization of nonlinear quarter car suspension–seat–driver mod

In this paper a nonlinear quarter car suspension–seat–driver model was implemented for optimum design. A nonlinear quarter car model comprising of quadratic tyre stiffness and cubic stiffness in suspension spring, frame, and seat cushion with 4 degrees of freedom (DoF) driver model was presented for optimization and analysis. Suspension system was aimed to optimize the comfort and health criterion comprising of Vibration Dose Value (VDV) at head, frequency weighted RMS head acceleration, crest factor, amplitude ratio of head RMS acceleration to seat RMS acceleration and amplitude ratio of upper torso RMS acceleration to seat RMS acceleration along with stability criterion comprising of suspension space deflection and dynamic tyre force. ISO 2631-1 standard was adopted to assess ride and health criterions. Suspension spring stiffness and damping and seat cushion stiffness and damping are the design variables. Non-dominated Sort Genetic Algorithm (NSGA-II) and Multi-Objective Particle Swarm Optimization – Crowding Distance (MOPSO-CD) algorithm are implemented for optimization. Simulation result shows that optimum design improves ride comfort and health criterion over classical design variables

Mapping of dwarfing gene Rht14 in durum wheat and its effect on seedling vigor, internode length and plant height

Short coleoptiles associated with GA-insensitive Rht-1 alleles in wheat reduces yield due to poor seedling establishment under dry, or stubble-retained conditions. Hence there is a need for alternative dwarfing genes for wheat improvement programs. GA-sensitive dwarfing gene Rht14 confers semidwarf stature in wheat while retaining longer coleoptiles and early seedling vigor. Two RIL populations were used to identify the map position of Rht14 and to estimate its effect on plant height, coleoptile length, seedling shoot length, spike length and internode length. Rht14 on chromosome 6A was mapped in the genomic region 383–422 Mbp flanked by GA2oxA9 and wmc753 in a Bijaga Yellow/Castelporziano RIL population. Recombination events between Rht14 and GA2oxA9 in the RIL population indicated that Rht14 might not be allelic to GA2oxA9. The conserved DNA sequence of GA2oxA9 and its flanking region in Castelporziano also suggested that the point of mutation responsible for the Rht14 allele must be a few Mbp away from GA2oxA9. The dwarfing effects of Rht14 on plant height, internode length and seedling vigor were compared with those of Rht-B1b in an HI 8498/Castelporziano RIL population. Both genes significantly reduced plant height and internode length. Rht-B1b conferred a significant reduction in coleoptile length and seedling shoot length, whereas Rht14 reduced plant height, but not coleoptile and seedling shoot length. Therefore, Rht14 can be a used as an alternative to Rht-B1b for development of cultivars suitable for deeper sowing in dry environments and in conditions of conservation agriculture where crop residues are retained. Keywords: Coleoptile length, Rht14, Semidwarf wheat, Triticum duru