Stiffening of Red Blood Cells Induced by Disordered Cytoskeleton Structures: A Joint Theory-experiment Study

The functions and elasticities of the cell are largely related to the structures of the cytoskeletons underlying the lipid bi-layer. Among various cell types, the Red Blood Cell (RBC) possesses a relatively simple cytoskeletal structure. Underneath the membrane, the RBC cytoskeleton takes the form of a two dimensional triangular network, consisting of nodes of actins (and other proteins) and edges of spectrins. Recent experiments focusing on the malaria infected RBCs (iRBCs) showed that there is a correlation between the elongation of spectrins in the cytoskeletal network and the stiffening of the iRBCs. Here we rationalize the correlation between these two observations by combining the worm-like chain (WLC) model for single spectrins and the Effective Medium Theory (EMT) for the network elasticity. We specifically focus on how the disorders in the cytoskeletal network affect its macroscopic elasticity. Analytical and numerical solutions from our model reveal that the stiffness of the membrane increases with increasing end-to-end distances of spectrins, but has a non-monotonic dependence on the variance of the end-to-end distance distributions. These predictions are verified quantitively by our AFM and micropipette aspiration measurements of iRBCs. The model may, from a molecular level, provide guidelines for future identification of new treatment methods for RBC related diseases, such as malaria infection.Comment: 8 pages, 4 figures; 3 supporting figure

A preliminary investigation into the effects of nonlinear response modification within coupled oscillators

This thesis provides an account of an investigation into possible dynamic interactions between two coupled nonlinear sub-systems, each possessing opposing nonlinear overhang characteristics in the frequency domain in terms of positive and negative cubic stiffnesses. This system is a two degree-of-freedom Duffing oscillator coupled in series in which certain nonlinear effects can be advantageously neutralised under specific conditions. This theoretical vehicle has been used as a preliminary methodology for understanding the interactive behaviour within typical industrial ultrasonic cutting components. Ultrasonic energy is generated within a piezoelectric exciter, which is inherently nonlinear, and which is coupled to a bar-horn or block-horn to one, or more, material cutting blades, for example. The horn/blade configurations are also nonlinear, and within the whole system there are response features which are strongly reminiscent of positive and negative cubic stiffness effects. The two degree-of-freedom model is analysed and it is shown that a practically useful mitigating effect on the overall nonlinear response of the system can be created under certain conditions when one of the cubic stiffnesses is varied. It has also bfeen shown experimentally that coupling of ultrasonic components with different nonlinear characteristics can strongly influence the performance of the system and that the general behaviour of the hypothetical theoretical model is indeed borne out in practice

Single molecule and multiple bond characterization of catch bond associated cytoadhesion in malaria

The adhesion of malaria infected red blood cells (iRBCs) to host endothelial receptors in the microvasculature, or cytoadhesion, is associated with severe disease pathology such as multiple organ failure and cerebral malaria. Malaria iRBCs have been shown to bind to several receptors, of which intercellular adhesion molecule 1 (ICAM-1) upregulation in brain microvasculature is the only one correlated to cerebral malaria. We utilize a biophysical approach to study the interactions between iRBCs and ICAM-1. At the single molecule level, force spectroscopy experiments reveal that ICAM-1 forms catch bond interactions with Plasmodium falciparum parasite iRBCs. Flow experiments are subsequently conducted to understand multiple bond behavior. Using a robust model that smoothly transitions between our single and multiple bond results, we conclusively demonstrate that the catch bond behavior persists even under flow conditions. The parameters extracted from these experimental results revealed that the rate of association of iRBC-ICAM-1 bonds are ten times lower than iRBC-CD36 (cluster of differentiation 36), a receptor that shows no upregulation in the brains of cerebral malaria patients. Yet, the dissociation rates are nearly the same for both iRBC-receptor interactions. Thus, our results suggest that ICAM-1 may not be the sole mediator responsible for cytoadhesion in the brain

Malaysia's ageing population : Viability of employment trust fund for retirement village

This study aims to analyse the Feasibility of Retirement Village for Malaysia.s Ageing Population. The analysis process involves assessing the level of awareness and opinion in the respondents of the demand for Retirement Village in Malaysia using survey method. At the macro level perspective, an overview analysis of the social, economic, political and technical knowhow of implementing and operating a Retirement Village has been taken into consideration to verify the advantages and disadvantages of the ultimate plan for Retirement Village. In order to satisfy the need for the public and acceptance of the idea to retire at Retirement Village, a detailed study and literature review of the practical reason for the implementation was intended to derive a mechanism for the suggested plan, to explore whether it to be workable in this country. Hence, a structured plan by private sector to establish a trust fund for Retirement Village as part of employee benefit was investigated to explore whether a potential demand and supply of the study is completely balanced. The motivation for the study was intended to build the first Retirement Village for the middle class elderly in Malaysia, therefore the senior citizens can enjoy a good lifestyle after retirement instead suffering from mental distress of living alone at their existing homes. The motivation is also partly due to the fact that the public general has a wrong perception that living in Retirement Village is the abandonment of parents by their loves ones which is completely wrong. The test itself would be able to confirm at the level information available to Malaysians and the knowledge they possessed about Retirement Village. There is much literature on Employee Loyalty, Motivation, Employee Benefits and Corporate Social Responsibility. However, there are no calls to extend the purpose of the literature study to apply in the companies in Malaysia to create economic and social value to the Malaysia Economic Productivity and Social Welfare improvement. This research is a comprehensive study because there is a recommendation to adapt Corporate Social Responsibility Core Value at Work Place to improve Employee Loyalty, increase Motivation and improve retention via the implementation of Employee Benefit to encourage the private sector to implement a Retirement Trust Fund for Retirement Village for their long-serving employees. As such, the retention of talents can be achieved due to better job security and loyalty. And, the employer can improve their productivity due to less time spent on retraining new employees and handling recruiting work from time to time. Due to the lack of availability of literature to assess the Feasibility of Retirement Trust Fund for Retirement Village in the context of Malaysia.s ageing population, this study can also motivate the researcher to explore further. The study herewith will be part of Greenfield study that requires further research in the future to confirm certain aspects of the findings. Further to that, this study is very relevant for Malaysia context because this is a pioneering research in the viability of Trust Fund for Retirement in Malaysia. Currently, there is no public or private owned Retirement Village being built in Malaysia which has motivate the researcher to take the challenge to assess the viability. The study involves relative demographic of the respondents in correlation to the knowledge and opinions of the Retirement Village. Generally, the study was carried out in Kuala Lumpur and Petaling Jaya, which is an Urban and Suburb respectively of Malaysia which comprises approximately 71 million populations. The respondents were mostly educated adults from different education backgrounds and various age groups to derive a good mix of sensible responses. Our result reveals that generally not all Malaysians are aware of the terminology of Retirement Village and not certain of the benefits living in the retirement village due to the lack of awareness and non-availability of the services in Malaysia. However, for those who are aware of the Retirement Village, they are basically receptive of the idea that it is a good place to adapt healthy, independent lifestyle retirement for senior citizen. From the overall result it reveals that the majority of the respondents from the ages of 31 to 40 look forward to retire in the Retirement Village and enjoy a community living lifestyle. This is despite the fact that these Malaysians are strong in Asian Extended Family Culture and they are also educated and married. The test also suggested that man are more independent in Malaysia and are very positive in Retirement Village lifestyle and single females surpassed married females in the preference to live in the Retirement Village. The research also concluded that three quarters (3/4) of the respondents have their opinions that their current Employee Provident Funds (EPF) is insufficient for their old age retirement, a total combined of 80.6% of the respondents have an opinion that private sectors should set up a trust fund for Retirement Village for their long serving employees, a combine total of 71% of the respondents have revealed that the Government should impose rules on private sectors to set up a trust fund for the Retirement Village for their long serving employees, an average combined 77% of the respondents have agreed that the Government should provide tax incentives to property developers to build Retirement Village and a combined average 71% of the respondents in their opinion that the Government should provide tax incentives to the tax payers for specific investment in the Retirement Village. Several implications arise from the study, firstly there is no supply in the building industry conglomerate that is willing to venture into this business unless it is certain that the monthly maintenance charges for the senior citizens are rest assured by their former employer or companies. Secondly, there is an issue of sustainability of the company to provide such a large scale employee benefit which is not feasible unless they adhere strictly to the CSR Core Values and there are more incentives cum tax subsidies from the policy maker to drive this purpose into reality. Thirdly, there is lack of expertise in the healthcare system in Malaysia that may require more time and money for training before the real implementation of the pilot project. Fourthly, the expectation from the Malaysian population now is already exists but there is no supply of the services. Lastly, the social economic changes, there are more going to have accelerated growth of singles, divorce group and single-child family in the population that require to live in the Retirement Village. This suggests critical reason that various preparation works such as training of expertise in healthcare services for senior citizens can be accelerated and increased

Cell division: a source of active stress in cellular monolayers

We introduce the notion of cell division-induced activity and show that the cell division generates extensile forces and drives dynamical patterns in cell assemblies. Extending the hydrodynamic models of lyotropic active nematics we describe turbulent-like velocity fields that are generated by the cell division in a confluent monolayer of cells. We show that the experimentally measured flow field of dividing Madin-Darby Canine Kidney (MDCK) cells is reproduced by our modeling approach. Division-induced activity acts together with intrinsic activity of the cells in extensile and contractile cell assemblies to change the flow and director patterns and the density of topological defects. Finally we model the evolution of the boundary of a cellular colony and compare the fingering instabilities induced by cell division to experimental observations on the expansion of MDCK cell cultures.Comment: Accepted Manuscript for Celebrating Soft Matter's 10th Anniversar

Task-Aware Asynchronous Multi-Task Model with Class Incremental Contrastive Learning for Surgical Scene Understanding

Purpose: Surgery scene understanding with tool-tissue interaction recognition and automatic report generation can play an important role in intra-operative guidance, decision-making and postoperative analysis in robotic surgery. However, domain shifts between different surgeries with inter and intra-patient variation and novel instruments' appearance degrade the performance of model prediction. Moreover, it requires output from multiple models, which can be computationally expensive and affect real-time performance. Methodology: A multi-task learning (MTL) model is proposed for surgical report generation and tool-tissue interaction prediction that deals with domain shift problems. The model forms of shared feature extractor, mesh-transformer branch for captioning and graph attention branch for tool-tissue interaction prediction. The shared feature extractor employs class incremental contrastive learning (CICL) to tackle intensity shift and novel class appearance in the target domain. We design Laplacian of Gaussian (LoG) based curriculum learning into both shared and task-specific branches to enhance model learning. We incorporate a task-aware asynchronous MTL optimization technique to fine-tune the shared weights and converge both tasks optimally. Results: The proposed MTL model trained using task-aware optimization and fine-tuning techniques reported a balanced performance (BLEU score of 0.4049 for scene captioning and accuracy of 0.3508 for interaction detection) for both tasks on the target domain and performed on-par with single-task models in domain adaptation. Conclusion: The proposed multi-task model was able to adapt to domain shifts, incorporate novel instruments in the target domain, and perform tool-tissue interaction detection and report generation on par with single-task models.Comment: Manuscript accepted in the International Journal of Computer Assisted Radiology and Surgery. codes available: https://github.com/lalithjets/Domain-adaptation-in-MT

Stepwise basis set selection

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146410/1/jcc25363.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146410/2/jcc25363_am.pd

Controlled biomineralization of electrospun poly(ε-caprolactone) fibers for enhancing their mechanical properties

Electrospun polymeric fibers have been investigated as scaffolding materials for bone tissue engineering. However, their mechanical properties, and in particular stiffness and ultimate tensile strength, cannot match those of natural bones. The objective of the study was to develop novel composite nanofiber scaffolds by attaching minerals to polymeric fibers using an adhesive material-the mussel-inspired protein polydopamine-as a superglue . Herein, we report for the first time the use of dopamine to regulate mineralization of electrospun poly(ε-caprolactone) (PCL) fibers to enhance their mechanical properties. We examined the mineralization of the PCL fibers by adjusting the concentration of HCO3 - and dopamine in the mineralized solution, the reaction time and the surface composition of the fibers. We also examined mineralization on the surface of polydopamine-coated PCL fibers. We demonstrated the control of morphology, grain size and thickness of minerals deposited on the surface of electrospun fibers. The obtained mineral coatings render electrospun fibers with much higher stiffness, ultimate tensile strength and toughness, which could be closer to the mechanical properties of natural bone. Such great enhancement of mechanical properties for electrospun fibers through mussel protein-mediated mineralization has not been seen previously. This study could also be extended to the fabrication of other composite materials to better bridge the interfaces between organic and inorganic phases

Viscoelastic Effects of Silicone Gels at the Micro- and Nanoscale

AbstractThere has been an increased use of silicone gel for applications such as cell traction force measurements as well as lab- and organ-on-chip systems. However, silicone gel is a viscoelastic material which tends to undergo non-elastic deformation and displays time-dependent and strain rate-dependent responses. Here, we evaluated the mechanical responses of two types of commonly used silicone gels, Sylgard-184 and CY52-276, when subjected to nanoNewton force and micrometer displacement length scales. Using different mechanical characterization tools and theoretical models, we characterized and quantified the viscoelastic parameters of these substrates. Our experimental results showed that silicone substrates with high stiffness and elasticity and negligible strain rate-dependency and creep responses will be most suited for use at the nanoNewton force and micrometer displacement length scales such as that encountered in cell traction force assays