Indian Institute of Science Bangalore
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Studies on Metal Hydride Based Multifunctional Coupled Thermal Battery Systems
No full textThermal energy storage systems (TESS) based on chemisorption/thermochemical reactions have several advantages over conventional thermal storage systems based on sensible and latent heat. The advantages include high energy storage densities, wide operating ranges, portability, and, most importantly, energy storage at ambient temperatures without incurring heat losses. Typical materials for thermochemical TESS include metal hydrides (MHs), salt hydrates, and ammoniated salts.
Among thermochemical-based TESS, metal hydrides have received significant attention. In these applications, the decomposition of MH into metal/alloy and hydrogen gas is an endothermic reaction that can be used to store heat, whereas the formation of MH is an exothermic reaction that can be used to recover the stored heat. Two distinct MH reactors are often required, one for thermal storage, referred to as an energy storage bed (ESB), and another for hydrogen storage, referred to as a hydrogen storage bed (HSB). These two reactor beds are dynamically coupled such that the hydrogen released from the ESB at high temperatures can be stored in the HSB during the charging process. For recovering the stored heat from the ESB (discharging process), hydrogen is released from the HSB using ambient heat and supplied to the ESB. The primary objective of this thesis is to investigate various design and operational aspects of coupled MH-TESS.
The first important task for the development of a coupled MH-TESS is the selection of thermodynamically compatible pairs of MHs. The MH for ESB is selected based on charging temperature and operating pressure. The corresponding MH for HSB is selected based on thermodynamic compatibility criteria. The criteria for the selection of a suitable pair of MH dictate that for the cyclic operation of a coupled MH-TESS, the pressure of the gas inside the ESB corresponding to its temperature should be higher than the pressure of the gas inside the HSB corresponding to its temperature during charging and vice versa during discharging. Thermodynamic compatibility is tested using the van’t Hoff equation within specified temperatures (charging temperature, discharging temperature, and ambient temperature). The minimum charging temperature and the maximum discharging temperature for a given pair of MHs at the specified ambient temperature are determined using the compatibility criteria. Following that, the mass and heat transfer characteristics of coupled MH-TESS through simulations are analyzed. MH-TESS can be operated in long-term and buffer modes, depending on the requirements. In long-term mode, the reactors are cooled down to room temperature, and heat is recovered from the ESB whenever required. Whereas, in buffer mode, the heat recovery process occurs without much time gap for its subsequent application, usually to cater for load fluctuations. The performance of a coupled MH-TESS in long-term and buffer modes is investigated using a pair of Mg2Ni-LaNi5 hydrides for high-temperature applications, where the former MH is used in ESB while the later MH is used in HSB. In addition to hydrogen storage and release, the low-temperature MH can also simultaneously produce a heating or cooling effect depending on charging or discharging. This multifunctionality of a coupled MH-TESS is also investigated using a medium-temperature MH (LaNi4.25Al0.75) for ESB, coupled with a low-temperature MH (LaNi5) used for HSB.
Based on theoretical and computational studies, the development of MH storage devices, the development of a hydrogen loop, and experimental investigations on individual and coupled reactors are carried out. As the effective thermal conductivity of hydride alloys is very low, typically in the order of 1 W.m-1.K-1, the design of the hydride beds becomes crucial for the performance of MH-TESS. A novel cartridge-type reactor is developed that offers a thin annular MH bed, a large surface area, and overall compactness. A test rig consisting of a heat transfer fluid (HTF) loop, a hydrogen gas loop, and a test section for mounting the cartridge reactors is fabricated. A silicone-based oil (Julabo-Thermal H20S) is used as HTF. The initial equilibrium state of coupled cartridges is crucial because, at this point, the ESB must be nearly saturated with hydrogen, whereas the HSB must be nearly free of hydrogen. A systematic method to arrive at the optimum initial equilibrium condition of coupled hydride beds is provided. After testing the performance of coupled MH-TESS, parametric studies are performed on the coupled reactors to study the sensitivity of the alloys to various operating conditions. Experimental investigations on the coupled reactors reveal that the charging temperature and the ambient temperature (where the low-temperature alloy in HSB is intended to operate) significantly affect the performance of the system. Also, it is found that the flow rate of HTF controls the heat delivery temperature. It is observed that the coupled MH-TESS with LaNi4.25Al0.75-La0.75Ce0.25Ni5 pair, delivers 227.7 kJ of heat at an average heat transfer rate of 130.7 W at the heat transfer fluid inlet temperature of 25℃, while also producing a cooling effect of 171.8 kJ with an average cooling rate of 103.5 W. Based on the above performance of a single module of a coupled MH-TESS, the system can be scaled-up for any practical application by arranging a required number of such cartridge-shaped reactors in a ‘shell-and-tube’ configuration
Secondary Atomization of a Droplet in Diverse Interaction Settings
No full textSecondary atomisation refers to the process by which liquid droplets, which are already in a dispersed state, are further atomised down into smaller droplets. This process occurs after primary atomisation, which is the initial breakup of a bulk liquid into droplets. Understanding and controlling secondary atomisation is crucial for optimising various industrial and natural applications. In this study, we investigate the secondary atomisation of a single droplet in three different interaction settings: shock waves, vortices, and porous surfaces (such as facemasks).
In shock-droplet interaction (first setting), the multiscale phenomenon is classified into two stages: wave dynamics (stage I) and droplet breakup dynamics (stage II). Stage I involves the formation of different wave structures after an incident shock impacts the droplet surface. Stage II involves induced airflow interaction with the droplet, leading to its deformation and breakup. Primarily, two modes of droplet breakup, i.e., shear-induced entrainment (SIE) and Rayleigh–Taylor piercing (RTP) (based on the modes of surface instabilities) are observed for the studied range of Weber numbers (We∼ 30 - 15000). A criterion for the convenient transition between two breakup modes is also discussed. For measurement of drop sizes during a shock-drop interaction process, the two-sensor depth from defocus (DFD) technique is further developed to achieve higher spatial and temporal resolution, to improve estimates of spatial size distribution and number concentration, and to provide additional guidelines for the calibration and design of the optical system for a specific application. Furthermore, the secondary atomisation of liquid metal droplets has been investigated using Galinstan as a test fluid. The study explores crucial questions, such as the applicability of atomisation results obtained from conventional fluids like DI water to liquid metal atomisation. The study sheds light on how surface oxidation of liquid metal plays a significant role in regulating atomisation dynamics and the shape of fragmented droplets.
In vortex-droplet interaction (second setting), we elucidate the mechanism of co-axial interaction of a droplet with a vortex ring of different circulation strengths (Γ = 45 - 161 cm^2 s^(-1)). We focus on both the droplet and the vortex dynamics, which evolve in a spatial and temporal fashion during different stages of the interaction, as in a two-way coupled system. In the droplet dynamics, different regimes of interaction are identified, including deformation (regime-I), stretching and engulfment (regime-II), and droplet breakup (regime-III). In vortex dynamics, we compare the interaction’s effect on different characteristics of the vortex rings. Vortex-droplet interaction leads to a reduction in these parameters.
In droplet porous-surface (facemask) interaction (third setting), we show that high-momentum, large-sized (>250 μm) surrogate cough droplets can penetrate single- or double-layer mask material to a significant extent. The penetrated droplets can atomise into numerous much smaller (<100 μm) droplets, which could remain airborne for a significant time. The possibility of secondary atomisation of high-momentum cough droplets by hydrodynamic focusing and extrusion through the microscale pores in the fibrous network of the single/double-layer mask material must be considered in determining mask efficacy. The results of droplet atomisation are compared in terms of droplet penetration, size distribution, and volume transmission. Theoretical models for the criteria of droplet penetration, breakup time, and droplet size prediction agree well with the experimental data.
To conclude the discussion, we investigate an interaction test case at a low Weber number value. In this scenario, we examine a periodic interaction between a vortex ring and a droplet, where surface tension force is dominant over inertial force (low Weber number), and secondary atomisation does not occur. This type of interaction has the potential to modify the droplet’s evaporation and crystallisation characteristics. Our findings reveal that the droplets’ evaporation characteristics depend on the strength of the vortex, while the crystallisation dynamics remain independent of it
Structural insights into the organization and channel behavior of Pannexin isoforms
Get PDFPannexins are large-pore ion channels structurally related to Connexins and Innexins but remain as hemichannels to release cellular ATP upon activation. Pannexins comprise three isoforms, Pannexin1, 2, and 3, with diverse cellular roles ranging from inflammation, differentiation, and neuropathic pain to ATP release. In this study, we report the Cryo-EM structure of Pannexin3 to draw insights into the effects on channel organization and function compared to the Pannexin1 isoform. The Pannexin3 isoform displays weak ATP binding but shows similar voltage dependence compared to Pannexin1.
We also report the structures of Pannexin1 congenital mutant R217H along with a Pannexin1 double mutant W74R/R75D that mimics Pannexin2 pore residues to a resolution range of 3.8-4.2Å. The mutant structures undergo minor structural changes to form a partially closed pore. The ATP binding analysis reveals weak binding affinity of the mutants compared to wild-type Pannexin1. Moreover, the congenital mutant displays altered voltage dependence compared to the wild type. The results signify the vital role of pore-lining residues and their role in affecting pore radius in dictating pannexins' architecture and channel behavior.DB
Entanglement properties of gauge theories and the graviton.
No full textEntanglement entropy is emerging as a useful quantity to study critical phenomena in quantum systems, black holes physics, and holography. In this presentation, we discuss entanglement properties of gauge theories and the graviton in the ground state as well as excited states corresponding to local quenches.
We show that the quantum entanglement entropy of the ground state of the free Maxwell field in d=4 dimensions, conformal p-forms, and conformal higher spins can be obtained from the partition function on the hyperbolic cylinder. We demonstrate that the entanglement entropy of linearized gravitons across a sphere coincides with that obtained from the partition function of Kaluza-Klein tower of traceless transverse massive spin-2 fields on the hyperbolic cylinder with the mass of the constant mode along S^1 direction saturating the Brietenholer-Freedman bound in AdS_3.
We show that the Gauss law of gravity implies that certain radial components of Riemann tensors label the super-selection sectors for the graviton. The classical or non-extractable part of the entanglement entropy is evaluated from the two-point functions of certain components of the Riemann tensors on S^2 which coincides with the logarithmic divergent piece of the `edge' partition function of the massless spin-2 field on the 4-sphere when written in terms of its Harish-Chandra character.
We develop a systematic procedure to evaluate the growth in entanglement entropies under local quenches created by free fields with spin, s ≤ 2. We show that in the zero-width limit of the quench, entanglement grows in time and then saturates at log(2) for free fields. The growth profile is determined by order 2s + 1 polynomials in the ratio of the distance from the co-dimension-2 entangling surface and time. The polynomials corresponding to quenches created by the fields can be organized in terms of their representations under the SO(2)_T X SO(2)_L symmetry preserved by the presence of the co-dimension-2 entangling surface
Low Head Hydraulic Pumping – Design, Simulation, and Field Validation of Ram and Turbine Pump in Indian River Basin
No full textWater energy is essential for economic expansion and human development. Social progress
and economic growth depend on meeting water energy needs sustainably. The use of non renewable energy sources for pumping water to high heads from a low head (surface flow or
groundwater) has led to a global imbalance, leaving society vulnerable to an uncertain future.
The thesis aims to bypass electrical energy for pumping water in a niche region of people near
river basins, promoting interdependence and minimizing consumption. Technical engineering
solutions applied in this work use the flow from rivers or streams as their primary input energy
sources to pump 5 to 10 percent of the water needed for sustenance at higher elevations while
returning 90 to 95 percent of the water that is used for pumping back to the stream. This
endeavour has the potential to assist around 5% of the world's population who currently live
along the river basins. The Taipadar village case study is illustrated, which is situated in the
Tiriya river basin of the Chhattisgarh state, Bastar, in central-east India, to demonstrate the
implementation of such technical solutions in the real world. The emphasis is given to the
effectiveness of converting two hydraulic powers: input river flow and head and output
delivered flow and delivery head.
Afterward, in this research, the two appropriate engineering solutions of the Taipadar village,
namely the Ram pump and Turbine pump, have been examined for their best performance, and
monograms have been created to enable technicians and field personnel to develop their
customized systems. A detailed comparison of two technologies (i.e., Ram pump and Turbine
pump) is made with a discussion of their working principles and the results of tests conducted
at a field station in central-east India. The H-Q-D (Head-Discharge-Diameter) chart is also
developed to serve as a helpful tool for interpreting the technology concerning boundary
circumstances and serves as a roadmap for upcoming innovations in such renewable hydro pumping devices.
It is crucial to investigate the technologies' combined or individual overall optimum
performance for the system design. To gain insights into the performance of the turbine pump,
its blade geometry, represented by the blade thickness to chord length ratio (t/l), is analysed.
This study on t/l highlights its effect on the specific speed of the turbine and, therefore, the
pumping efficiency. This comprehensive work on t/l is a novel area of investigation that has
been previously ignored or overlooked, but its findings have opened up new avenues for
optimizing the performance of hydro turbines. The scaling effect of axial flow propellers while
maintaining a constant t/l ratio, as well as varying chord lengths and blade numbers, is also
addressed. A comprehensive qualitative theory of energy transfer and corresponding loss
mechanisms is also provided, along with an analytical method.
Moreover, in order to examine the performance of a hydraulic ram, this study analysed the
stroke rate of the impulse valve, as well as the valve setting, drive head, and length, using two
analytical models. These models (i.e., Tacke and Iversen) have validated the results that show
good conformance with matching delivered flow. The analysis of the effect of control variables
on input variables demonstrates that the field setup outperformed the lab setup.
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The thesis, in the end, will provide the fundamentals, design, conceptualization, construction,
evaluation, and field validation guidelines for implementing low-head micro hydro pump
technologies to deliver water, generate electricity, and, most notably, convince society and
policymakers to shift their current reductionist approach. The scaling and design of the turbine
pump, pump selection, and flow output estimation with a technical-economic feasibility study
procedure are also discussed
Stability of wall-bounded compressible shear flows
No full textIn this work, the linear stability of compressible shear flows in channels and pipes are studied. A steady fully-developed laminar flow of an ideal gas, driven in a channel and a pipe by a constant body acceleration, is considered as the base state. The base flow profiles, being functions of Mach number, are obtained through numerical solution of the Navier-Stokes equations under steady parallel-flow conditions. Small amplitude normal mode perturbations are added to this flow and temporally growing solutions are studied. The evolution equations for the normal modes, that form a linear eigenvalue problem, are solved numerically by Chebyshev-Pseudospectral method.
For both channel and pipe flows, the eigenspectra show presence of compressible higher modes that do not have a counterpart in the incompressible limit. These modes are categorised into two distinct families based on the variation of the real part of their wave-speed with stream-wise wave-number. Numerical studies show the dominant instability at finite Mach numbers to be due to the modes that show a monotonic increase in the real part of the wave-speed with wave-number. These modes become unstable at finite wave-numbers at Mach numbers above a critical value. We have extended the classical stability theorems to compressible flows in bounded domains. A new criteria for the existence of neutral modes is derived which is used to obtain the values of the critical Mach numbers for the stability of the higher compressible modes.
In the incompressible limit, a pipe flow is stable to all modal perturbations, but the channel flow is unstable to the Tollmien-Schlichting (T-S) mode. Numerical studies at finite Mach numbers show compressibility to have a stabilising effect on the T-S mode. The critical Reynolds numbers as a function of Mach number are obtained for the all the unstable modes in both channel and pipe flows. A universal scaling of the critical values is shown at high Mach numbers. The critical Reynolds numbers for three-dimensional disturbances are also calculated for a compressible channel flow. It is shown that oblique waves are more unstable than two-dimensional waves with the minimum critical Reynolds number appearing at a specific wave-angle corresponding to a particular Mach number.
Numerical calculations of the stability equations are also performed in the inviscid limit where the numerical contour of integration is suitably chosen to avoid the branch point singularity at the critical point. The inviscid limit of the dominant compressible modes in channel and pipe flows compared against the high Reynolds number viscous calculations reveal the instabilities to be viscous in nature. The instability in channel and pipe flow appear due to a change in the viscous wall layer due to the emergence of a critical point very close to the wall.
The unstable modes in channel and pipe flows are studied at high Reynolds numbers through an asymptotic analysis. The instabilities in compressible channel flow are categorised into a small wave-number mode, which is the finite Mach number extension of the T-S mode, and finite wave-number modes, which are the dominant compressible higher modes. The asymptotic analysis for the lower and upper branches of the stability curve are performed to obtain the scalings for the wave-number, wave-speed, as well as the wall layer scalings for viscous regularization. An adjoint-based procedure imposing the solvability condition on the first and second correction to the stability equations, is devised to obtain the leading order eigenvalues for the lower and upper branches at high Reynolds numbers. The same asymptotic analysis is performed for the finite wave-number modes of the compressible pipe flow as well.
We also study the stability of a compressible flow in a channel with compliant walls. The compliant walls are modelled as spring-backed plates that move in the direction normal to the flow due to the fluid stresses acting at the walls. Wall compliance introduces additional instabilities, referred to as FSI modes, in addition to the Tollmien-Schlichting and compressible higher modes. The numerical studies indicate flow compressibility to have a stabilising effect on the FSI modes, and wall compliance to have a stabilising role on the compressible higher modes. Both flow compressibility and wall compliance are observed to have a stabilising effect on the Tollmien-Schlichting mode. We also calculate the perturbation energy budgets for the different instabilities which allow us to differentiate the different mechanisms of destabilisation of these modes
Towards the development of open-chip digital microfluidics platform
No full textManipulating and utilizing fluid flows at microscale provides several opportunities towards technological advancement in different domains such as (but not limited to) lab-on-chip devices for mimicking biological laboratory settings in an automated manner, wearable devices for continuous health monitoring, body-on-chip devices towards personalized medicine goal, electronics cooling techniques for efficient thermal management of semiconductor devices. Engineering such microscale fluid flow devices comes under the study of microfluidics. There has been various development in continuous, droplet and digital microfluidics approach. The microfluidic technology has potential to automate the laboratory procedures while reducing the sample and reagent consumption during analysis. However, there is plenty of room towards a fully integrated lab-on-chip platform comprising of all the steps such sample preparation, analyte separation/enrichments, detection, and final readouts.
In this doctoral work, an attempt has been made towards development of open digital microfluidics platform that can be integrated with channel-based microfluidic devices. The digital microfluidics techniques provide solution for automated sample preparation by manipulating discrete droplets on a planar substrate. While the channel-based devices are suitable for downstream analysis of samples e.g., single cell analysis. Thus, bringing together these two techniques of manipulating fluid will help in the development of integrated sampling and analysis device. However, the conventional digital microfluidics devices comprise of squeezed droplets using cover slips. This prevents accessibility to droplets and integration of other sampling and detection devices. Thus, open digital devices provide an alternative solution in which droplet is not covered from top side. There are different techniques to manipulate droplets such
as optical, surface acoustic wave (SAW), magnetic actuation and electro actuation. In this work, electrowetting-on-dielectric (EWOD) based digital microfluidics devices has been used. Open-chip droplet manipulation using electrowetting enables micro-total-analysis systems with multiple sensor integration and re-routing capabilities. In literature, researchers have explored unit processes like droplet transport and mixing on open-chip digital microfluidics platform. But splitting of droplet has always been considered as bottleneck. The splitting of droplet is crucial for sample separation and creating dilution ratio.
Initially, the challenge in open-chip droplet splitting is explored. An energy-based simulation modes is developed using surface evolver. It shows that splitting a sessile water droplet is impossible on an open-chip configuration because of the low pad contact angle requirement. Low contact angles cannot be achieved due to contact angle saturation in electrowetting. Further, the splitting of surfactant-loaded single-phase sessile droplets is presented and explain it using a preferential surface charging phenomenon
Later, an alternative solution has been proposed for droplet splitting using compound droplet (droplet is engulfed in an oil shell). The planar electrode configurations and regime of electrowetting numbers for which splitting can be achieved are identified. It was observed that larger gaps and higher electrowetting numbers favour symmetrical splitting because the electrostatic force driving the actuation is significantly higher than the retarding interfacial forces. Conversely, asymmetrical splitting has been obtained when the actuation force is barely sufficient.
In the later part of the thesis, a scalable open EWOD device is presented that can be used for study of multi-droplets non-coalescence phenomenon using compound droplets. The droplet non-coalescence is an interesting phenomenon that is observed in nature. This phenomenon of non-coalescence is slightly counter-intuitive as we expect liquid interfaces of the same surface tension to merge when they come in contact. However, with the help of modulating oil film in between the liquid interface, non-coalescence is observed for long durations. In this work, we have achieved the non-coalescence of multiple compound droplets on a coplanar EWOD device. The effect of droplet volume on the non-coalescence phenomenon has been studied in two-droplet
systems. We have obtained the non-coalescence regime map for different operating parameters of applied voltage and frequency. We have also explored three-droplet systems and obtained a non-coalescence regime.
For developing an integrated platform there is a need for channel-based sampling and analysis device which can be integrated with digital microfluidic sample preparation platform. However, for controlled sampling, in-situ pressure measurement is very important. The pressure measurement in a microfluidic device is useful for several other purposes as well such as fluid flow effect study on cells, measurement of mechanical properties of cells, etc. This work presents a cleanroom-free and simple technique to integrate pressure sensor in microfluidic devices. In this work, we demonstrated a novel technique of patterning Ti3C2-MXene on PDMS membrane using inkjet printing. We showed the piezoresistive response of inkjet printed MXene that has high sensitivity and can detect low strain value of 0.0003. The response time of the sensor is around 200 ms. The printed layer has been tested for 9000 cyclic loading for durability test and it shows very consistent behaviour. The printed MXene layer has been used as pressure sensor in closed-chip microfluidic device. We developed a simple way to integrate sensors by transferring thin PDMS layer followed by sensor integration using inkjet printing. Later, we demonstrated the applicability of our process to print Wheatstone bridge on microfluidic device to measure pressure. We also demonstrated touch sensor, temperature sensor and ultra-sensitive pressure sensor by using 8 microns thick PDMS membrane. This technique provides a way for localized pressure sensing in the microfluidic device with simple electrical readout and opens further prospect to study strain effect on endothelial cells, deformability of cells in microfluidic flow cytometry, etc.
In the future work, the complete idea of integrated platform is presented that has been envisioned to have multiple robotic limbs each armed with different sampling and analysis device
Functionalized Nanomaterial and Metallocycle for Selective Antibacterial, Diagnosis, and Anti-cancer Activity
No full textThe evolution of drug resistant bacteria has become a severe threat to public health globally. The misuse of conventional antibiotics has led to the development of multi-drug resistant bacteria. Even though antibiotics play a major role in modern medicine but the widely used antibiotics severely damage human-related microbial flora which ultimately result resistance in bacteria. To reduce the evolvement of drug resistance bacteria and minimize the side effects caused by nonspecific bactericidal action, it is necessary to develop strain-selective bactericidal strategies. The recent advancement in nanomaterials has encouraged us to utilize nanomaterials for the development of selective bactericidal agents. Transition metal dichalcogenides (TMDs) are a class of 2D layered materials with unique physicochemical properties. They have acquired great interest in various research fields such as electronic devices, sensors, catalysis, energy storage and more recently in biomedical applications. In typical, MoS2 a TMDs has attracted greater importance because of its desirable physical and chemical properties to utilize in biological applications. The easy surface functionalization, sharp edge, different phase with unique electronic properties of MoS2 helps to enhance their solution processibility as well as the biological interactions. Hence this chapter represents a collective literature background for the antibacterial activity of MoS2 nanomaterials and their nanocomposites. Also, the various methods of surface functionalization of MoS2 and their application in antibacterial activity were discussed. In addition, we have also discussed the protein and nanomaterial interaction for bio-analyte sensing. Finally, the antibacterial and anticancer activity of various nanostructured materials such as supramolecular cages, metal organic frameworks (MOF), and covalent organic frame works (COF)
A Study of Factors Influencing Need for, Mode of and Sustainability of New Urban Mobility
No full textGlobally, we are observing a paradigm shift in urban mobility enabled by the exponential growth in information and communication technologies (ICTs) leading to profound transformation from traditional mobility to other types of mobility. On the demand side, phenomena like working from home, on-demand entertainment, and online shopping could potentially reduce physical commuting – Virtual Mobility. On the supply side, ICTs enable new mobility options such as vehicle sharing and demand-responsive transport, thus potentially reducing vehicle ownership and use – Shared Mobility. Virtual and Shared mobility options accompanied by Traditional mobility modes are collectively called New Urban Mobility (NUM). Despite a large amount of empirical research over the last few decades, the fundamental issue about the influence of ICTs on mobility remains ambiguous. If all the conventional mobility needs are satisfied at home, will human beings be likely to generate new travel opportunities? If yes, the increased mobility volume can be beneficial if it leads to sustainable transport modes. This problem context requires a careful approach that gives due consideration to the attitudinal, perceptional, socio-economic, and cultural contexts. Thus, the research aims to explore the relationship between the individual, t= he ICTs, and urban mobility in three phases.
First, a conceptual framework was developed for understanding mobility behavior and its antecedents in the context of NUM. Mobility behaviors are conceptualized as a function of Attitudinal Factors, Contextual Factors, Personal Capabilities, and Demographic variables. Second, using the data from the primary survey, five distinct mobility behaviors were derived from Exploratory Factor Analysis (EFA). Internalized and externalized contextual indices were calculated for each mobility behavior. EFA on the attitudinal factors revealed six factors. Thereafter, multiple linear regression analysis was used to identify key variables influencing each identified mobility behavior. In the third phase, we segmented the Indian urbanites into three groups - Pragmatic Sceptics, Innovative Access Oriented and Green travel-oriented - based on the five identified mobility behaviors. These groups were then analyzed based on attitudinal factors, personal capabilities, and demographics. Finally, based on these results, important implications for policymakers, urban planners, and transportation companies were discussed, and future research directions were proposed
Role of autophagy in reducing peripheral neuropathy and diabetic peripheral neuropathy
No full textPeripheral neuropathy occurs when there is damage to the central or peripheral nervous system due to injury, disease, diabetes, or drug use. Endoplasmic reticulum (ER) stress is a distinct feature observed in neuropathic pain. Neuropathy is accompanied by changes in the levels of various proteins such as GSK-3β. GSK-3β not only regulates gluconeogenesis but also autophagy thus playing a key role in cellular physiology including proteostasis and autophagy. 6-bromoindirubin-3'-oxime (6-BIO) is an inhibitor of GSK-3β. Inhibition of GSK-3β results in inhibition of mTOR thereby activating autophagy. To understand the effect of ER stress and autophagy in alleviating pain, ER stress induced by tunicamycin was used to elicit pain in these studies. Chronic Diabetic animal model was also used to investigate diabetic peripheral neuropathy. Tunicamycin blocks N-linked glycosylation leading to ER stress. As ER stress is one of the hallmarks of neuropathic pain, we have used intraplantar injection of tunicamycin to induce neuropathic pain. Peripheral neuropathy induced by tunicamycin and that during chronic diabetes was observed to be reduced upon treatment with 6-BIO in rat as well as mice models. To substantiate the involvement of ER stress in pathway intrinsic to neuropathic pain and the role of autophagy in mitigating it, SH-SY5Y neurons were used as a model system. Western blot, RT-PCR, and fluorescence microscopy were deployed to study the effect of 6-BIO in modulating ER stress and autophagy in SH-SY5Y neurons pre-treated with tunicamycin. p-mTOR, is a widely used marker for examining ER stress and autophagy, hence its upregulation denotes occurrence of ER stress, and its down regulation indicates autophagy. It was observed that the level of p-mTOR was increased in SH-SY5Y neuronal cells upon treatment with tunicamycin implying a reduction in autophagy. But when 6-BIO was added to the cells already treated with tunicamycin there was a reduction in the level of p-mTOR showing that 6-BIO increased autophagy in cells already treated with tunicamycin. Additionally, decrease in expression of protein markers like LC-3 and SQSTM1/p62 after treatment with 6-BIO in cells pre-treated with tunicamycin shows that the autophagic flux is increased. Upregulation of markers like Beclin1 (BECN1) and LC3 by RT-PCR confirmed an increase in autophagy upon treatment with 6-BIO in presence of tunicamycin. Further assessment to delineate the type of autophagy that was being upregulated by 6-BIO, use of markers like Cathepsin D (CTSD) for degradative autophagy and Rab8A for secretory autophagy showed that secretory autophagy was increased by tunicamycin, while degradative autophagy was increased and at the same time secretory autophagy was reduced when 6-BIO was given after tunicamycin treatment. This shows that 6-BIO treatment of cells under ER stress leads to the formation of autolysosome leading to the degradation of damaged proteins thereby reducing cellular burden caused by ER stress, thus leading to mitigation of pain. A major contributing factor to the effect of tunicamycin in increasing pain is the increased ER stress. By using markers ER stress (CHOP and GRP78) it was observed that 6-BIO treatment in SH-SY5Y cells could reduce the ER stress caused by tunicamycin. Unregulated ER stress leads to apoptosis of cells which further exacerbates the effect of ER stress. Caspase-3 (a marker for apoptosis) was used to assess the effect of 6-BIO on apoptosis. 6-BIO in presence of tunicamycin reduced the protein expression of caspase-3 when compared to only tunicamycin treated cells. Thus, 6-BIO blocks apoptosis resulting from tunicamycin induced ER stress. c-fos is upregulated during neuronal activity including neuropathic pain hence it was used as a marker to verify the occurrence of neuropathy in these neurons by ER stress and its mitigation by increased autophagic flux. The expression of c-fos was increased when treated with tunicamycin and the addition of 6-BIO in tunicamycin background reduced the expression of c-fos. The change in c-fos confirms the observations of behavioral studies which show that tunicamycin increases neuropathy and treatment with 6-BIO after tunicamycin reduced pain. From reported studies it is known that 6-BIO inhibits the activity GSK-3β which is likely to also affect the mobilization of calcium. Further, calcium is an important secondary messenger in neuronal signaling and its levels are altered in neuropathy and diabetic neuropathy. In the current study it is shown that treatment with tunicamycin increases the mobilization of calcium in SH-SY5Y neuronal cells and DRG neurons due to perturbation of ER homeostasis. But when SH-SY5Y cells and DRG neurons are treated with 6-BIO before or after tunicamycin treatment show that the mobilization of calcium is reduced. Also, a reduction of mitochondrial calcium was seen in SH-SY5Y cells when treated with 6-BIO after treatment with tunicamycin. The reduction of calcium mobilization by 6-BIO in tunicamycin background might help in alleviating pain consistent with earlier studies on the causal role of an increase in calcium in peripheral neuropathy. In summary, 6-BIO helps in reducing neuropathic pain caused by tunicamycin and diabetic neuropathy and it does so by reducing ER stress and apoptosis, increasing autophagy, and preventing calcium mobilization.
In appendix chapter preliminary experiments are performed to explore the possibility of treating ER stress induced neuropathy by using an activator of Nrf2 – a transcription factor involved in modulating the neuronal redox state