Mammalian Systems Biotechnology Reveals Global Cellular Adaptations in a Recombinant CHO Cell Line

Yusufi, F.N.K.,Lakshmanan, M.,Ho, Y.S.,Loo, B.L.W.,Ariyaratne, P.,Yang, Y.,Ng, S.K.,Tan, T.R.M.,Yeo, H.C.,Lim, H.L.,Ng, S.W.,Hiu, A.P.,Chow, C.P.,Wan, C.,Chen, S.,Teo, G.,Song, G.,Chin, J.X.,Ruan, X. Cell Press 2017 Cell systems Vol.4 No.5

Effective development of host cells for therapeutic protein production is hampered by the poor characterization of cellular transfection. Here, we employed a multi-omics-based systems biotechnology approach to elucidate the genotypic and phenotypic differences between a wild-type and recombinant antibody-producing Chinese hamster ovary (CHO) cell line. At the genomic level, we observed extensive rearrangements in specific targeted loci linked to transgene integration sites. Transcriptional re-wiring of DNA damage repair and cellular metabolism in the antibody producer, via changes in gene copy numbers, was also detected. Subsequent integration of transcriptomic data with a genome-scale metabolic model showed a substantial increase in energy metabolism in the antibody producer. Metabolomics, lipidomics, and glycomics analyses revealed an elevation in long-chain lipid species, potentially associated with protein transport and secretion requirements, and a surprising stability of N-glycosylation profiles between both cell lines. Overall, the proposed knowledge-based systems biotechnology framework can further accelerate mammalian cell-line engineering in a targeted manner.

Facile, Morphology-Controlled and Mass Production of 0D-Ag/2D-g-C3N4/3D-TiO2 Nano-Composite Materials: Effect of Silver Morphology and Loading on the Electrochemical Performance

R. Ranjithkumar,P. Lakshmanan,N. Palanisami,P. Devendran,N. Nallamuthu,S. Sudhahar,M. Krishna Kumar 대한금속·재료학회 2023 ELECTRONIC MATERIALS LETTERS Vol.19 No.2

The 0D-Ag/2D-g-C3N4/3D-TiO2 nano-composite materials were fabricated by simple and mass production method. It involvesthe combination of incipient wetness impregnation and thermal spreading techniques. By changing the order of impregnationand thermal spreading, silver nanoparticles with “on-top” and “embedded” morphologies could be selectively controlled. Thethermal spreading followed by impregnation (TS-IM) leads to the “on-top” structure [Ag/g-C3N4/TiO2] while, the reverseorder (IM-TS) produces the embedded silver nanoparticles [g-C3N4/Ag/TiO2]. The 16%Ag/g-C3N4/TiO2 (TS-IM) sampleexhibited the best performance due to the presence of very small and highly dispersed silver nanoparticles over g-C3N4/TiO2 sample. The loading of silver not only doubled the specific capacitance but also stabilized the recycling performanceagainst deactivation. This study reveals easy and performance tunable synthesis of Ag/g-C3N4/TiO2 nano-composite materialstowards energy-storage applications.

Wavelet analysis and enhanced damage indicators

Lakshmanan, N.,Raghuprasad, B.K.,Muthumani, K.,Gopalakrishnan, N.,Basu, D. Techno-Press 2007 Smart Structures and Systems, An International Jou Vol.3 No.1

Wavelet transforms are the emerging signal-processing tools for damage identification and time-frequency localization. A small perturbation in a static or dynamic displacement profile could be captured using multi-resolution technique of wavelet analysis. The paper presents the wavelet analysis of damaged linear structural elements using DB4 or BIOR6.8 family of wavelets. Starting with a localized reduction of EI at the mid-span of a simply supported beam, damage modeling is done for a typical steel and reinforced concrete beam element. Rotation and curvature mode shapes are found to be the improved indicators of damage and when these are coupled with wavelet analysis, a clear picture of damage singularity emerges. In the steel beam, the damage is modeled as a rotational spring and for an RC section, moment curvature relationship is used to compute the effective EI. Wavelet analysis is performed for these damage models for displacement, rotation and curvature mode shapes as well as static deformation profiles. It is shown that all the damage indicators like displacement, slope and curvature are magnified under higher modes. A localization scheme with arbitrary location of curvature nodes within a pseudo span is developed for steady state dynamic loads, such that curvature response and damages are maximized and the scheme is numerically tested and proved.

Experimental, numerical and analytical studies on a novel external prestressing technique for concrete structural components

N. Lakshmanan,S. Saibabu,A. Rama Chandra Murthy,S. Chitra Ganapathi,R. Jayaraman,R. Senthil 사단법인 한국계산역학회 2009 Computers and Concrete, An International Journal Vol.6 No.1

This paper presents the details of a novel external prestressing technique for strengthening of concrete members. In the proposed technique, transfer of external force is in shear mode on the end block thus creating a complex stress distribution and the required transverse prestressing force is lesser compared to conventional techniques. Steel brackets are provided on either side of the end block for transferring external prestressing force and these are connected to the anchor blocks by expansion type anchor bolts. In order to validate the technique, an experimental investigation has been carried out on post-tensioned end blocks. Performance of the end blocks have been studied for design, cracking and ultimate loads. Slip and slope of steel bracket have been recorded at various stages during the experiment. Finite element analysis has been carried out by simulating the test conditions and the responses have been compared. From the analysis, it has been observed that the computed slope and slip of the steel bracket are in good agreement with the corresponding experimental observations. A simplified analytical model has been proposed to compute load-deformation of the loaded steel bracket with respect to the end block. Yield and ultimate loads have been arrived at based on force/moment equilibrium equations at critical sections. Deformation analysis has been carried out based on the assumption that the ratio of axial deformation to vertical deformation of anchor bolt would follow the same ratio at the corresponding forces such as yield and ultimate. It is observed that the computed forces, slip and slopes are in good agreement with the corresponding experimental observations.

Damage evaluation through radial basis function network based artificial neural network scheme

Lakshmanan, N.,Raghuprasad, B.K.,Muthumani, K.,Gopalakrishnan, N.,Basu, D. Techno-Press 2008 Smart Structures and Systems, An International Jou Vol.4 No.1

Seismic damage estimation through measurable dynamic characteristics

N. Lakshmanan,B. K. Raghuprasad,K. Muthumani,N. Gopalakrishnan,R. Sreekala 한국계산역학회 2007 Computers and Concrete, An International Journal Vol.4 No.3

Ductility based design of reinforced concrete structures implicitly assumes certain damage under the action of a design basis earthquake. The damage undergone by a structure needs to be quantified, so as to assess the post-seismic reparability and functionality of the structure. The paper presents an analytical method of quantification and location of seismic damage, through system identification methods. It may be noted that soft ground storied buildings are the major casualties in any earthquake and hence the example structure is a soft or weak first storied one, whose seismic response and temporal variation of damage are computed using a non-linear dynamic analysis program (IDARC) and compared with a normal structure. Time period based damage identification model is used and suitably calibrated with classic damage models. Regenerated stiffness of the three degrees of freedom model (for the three storied frame) is used to locate the damage, both on-line as well as after the seismic event. Multi resolution analysis using wavelets is also used for localized damage identification for soft storey columns.

Comparative study on damage identification from Iso-Eigen-Value-Change contours and smeared damage model

N. Lakshmanan,B.K. Raghuprasad,N. Gopalakrishnan,R. Sreekala,G.V. Rama Rao 국제구조공학회 2010 Structural Engineering and Mechanics, An Int'l Jou Vol.35 No.6

The paper proposes two methodologies for damage identification from measured natural frequencies of a contiguously damaged reinforced concrete beam, idealised with distributed damage model. The first method identifies damage from Iso-Eigen-Value-Change contours, plotted between pairs of different frequencies. The performance of the method is checked for a wide variation of damage positions and extents. The method is also extended to a discrete structure in the form of a five-storied shear building and the simplicity of the method is demonstrated. The second method is through smeared damage model, where the damage is assumed constant for different segments of the beam and the lengths and centres of these segments are the known inputs. First-order perturbation method is used to derive the relevant expressions. Both these methods are based on distributed damage models and have been checked with experimental program on simply supported reinforced concrete beams, subjected to different stages of symmetric and un-symmetric damages. The results of the experiments are encouraging and show that both the methods can be adopted together in a damage identification scenario.

Comparative study on damage identification from Iso-Eigen-Value-Change contours and smeared damage model

Lakshmanan, N.,Raghuprasad, B.K.,Gopalakrishnan, N.,Sreekala, R.,Rama Rao, G.V. Techno-Press 2010 Structural Engineering and Mechanics, An Int'l Jou Vol.35 No.6

The paper proposes two methodologies for damage identification from measured natural frequencies of a contiguously damaged reinforced concrete beam, idealised with distributed damage model. The first method identifies damage from Iso-Eigen-Value-Change contours, plotted between pairs of different frequencies. The performance of the method is checked for a wide variation of damage positions and extents. The method is also extended to a discrete structure in the form of a five-storied shear building and the simplicity of the method is demonstrated. The second method is through smeared damage model, where the damage is assumed constant for different segments of the beam and the lengths and centres of these segments are the known inputs. First-order perturbation method is used to derive the relevant expressions. Both these methods are based on distributed damage models and have been checked with experimental program on simply supported reinforced concrete beams, subjected to different stages of symmetric and un-symmetric damages. The results of the experiments are encouraging and show that both the methods can be adopted together in a damage identification scenario.

Dynamic stiffness based computation of response for framed machine foundations

Lakshmanan, N.,Gopalakrishnan, N.,Rama Rao, G.V.,Sathish kumar, K. Techno-Press 2009 Geomechanics & engineering Vol.1 No.2

The paper deals with the applications of spectral finite element method to the dynamic analysis of framed foundations supporting high speed machines. Comparative performance of approximate dynamic stiffness methods formulated using static stiffness and lumped or consistent or average mass matrices with the exact spectral finite element for a three dimensional Euler-Bernoulli beam element is presented. The convergence of response computed using mode superposition method with the appropriate dynamic stiffness method as the number of modes increase is illustrated. Frequency proportional discretisation level required for mode superposition and approximate dynamic stiffness methods is outlined. It is reiterated that the results of exact dynamic stiffness method are invariant with reference to the discretisation level. The Eigen-frequencies of the system are evaluated using William-Wittrick algorithm and Sturm number generation in the $LDL^T$ decomposition of the real part of the dynamic stiffness matrix, as they cannot be explicitly evaluated. Major's method for dynamic analysis of machine supporting structures is modified and the plane frames are replaced with springs of exact dynamic stiffness and dynamically flexible longitudinal frames. Results of the analysis are compared with exact values. The possible simplifications that could be introduced for a typical machine induced excitation on a framed structure are illustrated and the developed program is modified to account for dynamic constraint equations with a master slave degree of freedom (DOF) option.

Identification of reinforced concrete beam-like structures subjected to distributed damage from experimental static measurements

N. Lakshmanan,B. K. Raghuprasad,K. Muthumani,N. Gopalakrishnan,D. Basu 사단법인 한국계산역학회 2008 Computers and Concrete, An International Journal Vol.5 No.1

Structural health monitoring of existing infrastructure is currently an important field of research, where elaborate experimental programs and advanced analytical methods are used in identifying the current state of health of critical and important structures. The paper outlines two methods of system identification of beam-like reinforced concrete structures representing bridges, through static measurements, in a distributed damage scenario. The first one is similar to the stiffness method, re-cast and the second one to flexibility method. A least square error (LSE) based solution method is used for the estimation of flexural rigidities and damages of simply supported, cantilever and propped cantilever beam from the measured deformation values. The performance of both methods in the presence of measurement errors is demonstrated. An experiment on an un-symmetrically damaged simply supported reinforced concrete beam is used to validate the developed method. A method for damage prognosis is demonstrated using a generalized, indeterminate, propped cantilever beam.