66 research outputs found
Computational study of the structure and function of membrane transport proteins
No full textTransport of the nutrients across the cell membrane is regulated by membrane transport proteins which selectively and efficiently transports materials across the membrane. In the present work I focus on the family of membrane transporters the so called sugar porters in both their mammalian and bacterial forms. In the first work I describe the entire thermodynamic cycle of the GLUT1, a glucose transporter from the sugar porter family by employing non-equilibrium MD simulation and determining the free energy landscape associated with the so called IF–OF transition. Employing the information from the free energy calculations and equilibrium MD simulations from the members of the sugar porter family I present a unified mechanism of transport for the uniporter class of transporters. A second class of transporters namely symporters that couple the electrochemical gradient of a co transported ion to perform the uphill transport of the substrate was also studied. Using the H+-coupled Xylose transporter XylE a close homologue of GLUTs, as a prototypical symporter the allosteric effects of the binding of H+ and the subsequent effect on the substrate dynamics is studied. Furthermore, I explored the role of lipids in regulating the conformational equilibrium in XylE. In combination with HD-MS experiments we show that the nature of lipid protein interactions determined the stability of a particular conformational state of XylE. Continuing on the theme of lipid-protein interaction, I present my work on the P2X receptor, a non selective cation channel, where we present a unique ion permeation mechanism where the ion permeation pathway is formed by both protein and the lipid molecules.
In recent times, Cryo-EM has emerged as a tool for structural biologists to obtain structures of macro molecules which were previously difficult to elucidate using traditional methods. Employing MD simulations particularly Molecular Dynamics Flexible Fitting (MDFF) in its resolution exchange flavor ReMDFF, I present the results of the 2015-2016 Cryo-EM Model challenge. In this challenge that I participated, we employed the aforementioned methodologies to forward the field of structure determination from the density maps at 3-5 °A resolution. The results presented are focused on providing structures for the proteins TRPV1 & -galactosidase. However, all these approaches, including our popular Molecular Dynamics Flexible Fitting (MDFF), and its various extensions work under the conventional molecular replacement paradigm, whereby any initial search model is morphed to satiate the data-imposed constraints. As a natural consequence, quality of the determined model remains heavily biased by choices of the initial model. Here, we deliver a novel modeling pipeline, MMR (MAINMAST-MELD-ReMDFF) that interactively combines minimum spanning tree-based backbone tracing tool (MAINMAST), Bayesian-likelihood based protein-folding methodology (MELD), and a resolution exchange-based fitting protocol (ReMDFF). Starting from only sequence information, the algorithm places C atoms into the density, fits a random coil to this C trace, generates protein secondary structures on-the-fly, and exhaustively samples the backbone and side chain geometries to deliver a re-fined model. Overcoming limitations of traditional approaches, the need for an initial model or homology information is completely subsided, and de-novo modeling is now made feasible even at low resolutions.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2021-05-01The student, Mrinal Shekhar, accepted the attached license on 2019-02-12 at 13:10.The student, Mrinal Shekhar, submitted this Dissertation for approval on 2019-02-12 at 13:25.This Dissertation was approved for publication on 2019-02-15 at 11:27.DSpace SAF Submission Ingestion Package generated from Vireo submission #13386 on 2019-08-22 at 15:04:02Made available in DSpace on 2019-08-23T20:28:06Z (GMT). No. of bitstreams: 2
SHEKHAR-DISSERTATION-2019.pdf: 116370723 bytes, checksum: c06438d017f7d904447195ed297bfc31 (MD5)
LICENSE.txt: 4211 bytes, checksum: b92e1e929b7d358aa803182108cacd9e (MD5)
Previous issue date: 2019-02-15Embargo set by: Seth Robbins for item 112081
Lift date: 2021-08-23T20:28:11Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 112081
Lift date: 2021-08-23T20:29:33Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemEmbargo set by: Seth Robbins for item 112081
Lift date: 2021-08-23T20:36:18Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Only Restriction Lifted for Item 112081 on 2021-08-24T09:15:34Z
Chronicling the Self: A Feminist Approach to Mrinal Pande's Daughter's Daughter
No full textAutobiography writing is a means for women writers to explore their inner-most recesses of their selves. Mrinal Pande's Daughter's Daughter is a rare type of the portrayal of self-wherein the author creates a fictional self to describe her survival story of being a daughter's daughter. In the autobiography the author maintains a distance with her own self, speaking through a girl of the age span f two to ten. In the story of her 'self', Mrinal Pande, introspects, observes, comments and narrates her past through her mouthpiece, Tinu. The present paper focuses in detail the pain of being a girl child in a patriarchal society and the author's decision not to be a victim of patriarchal domination. 
Direct protein-lipid interactions shape the conformational landscape of secondary transporters
No full textSecondary transporters undergo structural rearrangements to catalyze substrate translocation across the cell membrane – yet how such conformational changes happen within a lipid environment remains poorly understood. Here, we combine hydrogen-deuterium exchange mass spectrometry (HDX-MS) with molecular dynamics (MD) simulations to understand how lipids regulate the conformational dynamics of secondary transporters at the molecular level. Using the homologous transporters XylE, LacY and GlpT from Escherichia coli as model systems, we discover that conserved networks of charged residues act as molecular switches that drive the conformational transition between different states. We reveal that these molecular switches are regulated by interactions with surrounding phospholipids and show that phosphatidylethanolamine interferes with the formation of the conserved networks and favors an inward-facing state. Overall, this work provides insights into the importance of lipids in shaping the conformational landscape of an important class of transporters
Computational study of the structure and function of membrane transport proteins
No full textTransport of the nutrients across the cell membrane is regulated by membrane transport proteins which selectively and efficiently transports materials across the membrane. In the present work I focus on the family of membrane transporters the so called sugar porters in both their mammalian and bacterial forms. In the first work I describe the entire thermodynamic cycle of the GLUT1, a glucose transporter from the sugar porter family by employing non-equilibrium MD simulation and determining the free energy landscape associated with the so called IF–OF transition. Employing the information from the free energy calculations and equilibrium MD simulations from the members of the sugar porter family I present a unified mechanism of transport for the uniporter class of transporters. A second class of transporters namely symporters that couple the electrochemical gradient of a co transported ion to perform the uphill transport of the substrate was also studied. Using the H+-coupled Xylose transporter XylE a close homologue of GLUTs, as a prototypical symporter the allosteric effects of the binding of H+ and the subsequent effect on the substrate dynamics is studied. Furthermore, I explored the role of lipids in regulating the conformational equilibrium in XylE. In combination with HD-MS experiments we show that the nature of lipid protein interactions determined the stability of a particular conformational state of XylE. Continuing on the theme of lipid-protein interaction, I present my work on the P2X receptor, a non selective cation channel, where we present a unique ion permeation mechanism where the ion permeation pathway is formed by both protein and the lipid molecules.
In recent times, Cryo-EM has emerged as a tool for structural biologists to obtain structures of macro molecules which were previously difficult to elucidate using traditional methods. Employing MD simulations particularly Molecular Dynamics Flexible Fitting (MDFF) in its resolution exchange flavor ReMDFF, I present the results of the 2015-2016 Cryo-EM Model challenge. In this challenge that I participated, we employed the aforementioned methodologies to forward the field of structure determination from the density maps at 3-5 °A resolution. The results presented are focused on providing structures for the proteins TRPV1 & -galactosidase. However, all these approaches, including our popular Molecular Dynamics Flexible Fitting (MDFF), and its various extensions work under the conventional molecular replacement paradigm, whereby any initial search model is morphed to satiate the data-imposed constraints. As a natural consequence, quality of the determined model remains heavily biased by choices of the initial model. Here, we deliver a novel modeling pipeline, MMR (MAINMAST-MELD-ReMDFF) that interactively combines minimum spanning tree-based backbone tracing tool (MAINMAST), Bayesian-likelihood based protein-folding methodology (MELD), and a resolution exchange-based fitting protocol (ReMDFF). Starting from only sequence information, the algorithm places C atoms into the density, fits a random coil to this C trace, generates protein secondary structures on-the-fly, and exhaustively samples the backbone and side chain geometries to deliver a re-fined model. Overcoming limitations of traditional approaches, the need for an initial model or homology information is completely subsided, and de-novo modeling is now made feasible even at low resolutions.U of I OnlyAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD syste
Performance of an internally cooled and heated desiccant-coated heat and mass exchanger: Effectiveness criteria and design methodology
No full textInternally cooled and heated desiccant-coated heat and mass exchangers (ICHDHMX) driven by low-grade heat are very attractive owing to their energy-saving potential, especially for applications where substantial moisture removal (such as air-conditioning) is a necessity. In this paper, we derive equations for the performance of an ideal ICHDHMX, allowing us to define humidity-ratio effectiveness (εY) and relative-humidity effectiveness (εRH) such that their values approach 1 as the performance approaches that of an ideal ICHDHMX. Besides an equation-based approach, an easy-to-use psychrometric-chart based approach is presented to determine the performance of an ideal ICHDHMX. We invoke conservation principles to ascertain whether or not it is feasible to use the ICHDHMX for a given set of inlet conditions of air and water streams for dehumidification and regeneration. The dimensions of the ICHDHMX can be determined using this methodology, not even requiring knowledge of a tuning parameter unless a precise outlet specific humidity is required. Simulations are conducted for cases involving three incoming hot water temperatures (38, 44 and 50 °C) and several mixing ratios of room return air (25 °C at 0.011 kg/kg dry air) and outdoor air (32 °C at 0.02 kg/kg dry air), typical of warm and humid weather conditions. For all cases, the cool-water inlet is fixed at 30 °C. The results show that even when the dehumidification air-stream humidity is high, if the regeneration air-stream humidity is low (typical of room-exhaust air), the operation of an ICHDHMX is feasible using a low regeneration temperature of only 38 °C. When the regeneration temperature is 50 °C, the exchanger can operate under the complete range of humidity conditions tested. A cooling coefficient of performance up to 9.8 and effectiveness value up to 0.88 is realized, while the fluid power required is generally very low. These findings substantiate the case for commercial adoption of this technology for air-conditioning.Accepted Author ManuscriptComplex Fluid Processin
Bullous cutaneous larva migrans – A case report
No full textAbstractCutaneous larva migrans (CLM) is a skin infestation commonly seen in tropical and subtropical geographic areas, caused by nematode larvae, usually of animal hookworms. Clinically it is characterized by erythematous serpiginous lesions, which are associated with severe itching which may lead to excoriations and secondary bacterial infection. Rarely, it may manifest as vesicobullous lesions or folliculitis. Herein, we present a case of bullous cutaneous larva migrans in a 60-year old farmer who was successfully treated with albendazole and ivermectin
Designing Circular Applications of Mycelium-Based Materials for Aircraft Cabins
No full textThis graduation project (Hyfen) elucidates opportunities for mycelium-based innovations in circular aircraft cabin design with a focus on material properties, applications and comparative environmental impacts.Aircraft cabin interior elements account for 10% of an aircraft’s empty weight, and are replaced 4-5 times during the lifetime of an airframe. Thus, cabin elements are responsible for a significant portion of an airliner’s environmental impacts due to operational emissions and improper waste handling. An understanding of the need to apply circular principles to the cabin led toheightened interest in mycelium-based materials which are lightweight and biodegradable.The design goals were 1) Understanding the material properties of mycelium-based materials based on aircraft cabin requirements 2) Identifying optimal applications of mycelium-based materials in an aircraft cabin and developing selected demonstrators & detailed designs 3) Assessing the circularity and comparative Life Cycle Impacts of selected applications.These goals were achieved through an adaptation of the Material Driven Design methodology. The outcomes of this project included conceptual design and demonstrators of two applications. First, is an optimized bionic partition with mycelium acoustic panels and filler material, weighing 40% less (41,6 kg) than a conventional nomex honeycomb-based composite partition (67 kg). The second is a modular packaging cum meal tray for airlines, aiming to reduce single-use plastic waste. These specific applications were detailed to highlight the temporal & versatile properties such as competitive insulation (acoustic & impact), damage-resistant textures, foam-like compressive properties, mouldability into complex shapes and comfortable tactile interactions for passengers. They also have a high potential to mitigate the environmental impacts of an aircraft cabin due to weight savings in the bulky interior panels, as demonstrated by a final circularity and fast-track life cycle assessment.Takeaways from this thesis also include insights into the optimal application families, including hot & cool cases, galley, business class & first class seat shelving systems, cushions and upholstery for seats and even decorative filler material for armrests and accessories. These applications to different degrees, leverage the unique material properties (e.g. low weight, mouldability, apparent sustainable advantage, warm & comforting textures etc.) of pure mycelium andmyco-composite materials. It also adds to an understanding of the design requirements for circular applications using mycelium derivatives and aims to inspire further research & development for deployment.This thesis provided conclusive foundational qualitative evidence on the potential environmental advantage of mycelium applications over plastics, composites and other petroleum-derived materials in an aircraft cabin. Future recommendations include looking into standardization, commercialization, usability and acceptance. Project Hyfen aimed to be visionary and embolden the stringent aerospace sector to seek solutions in nature for its circularity transition - with biobased materials like mycelium being the building blocks, literally and figurativelyInterdisciplinary Thesis Labs, Leiden Delft Erasmus Centre for SustainabilityIntegrated Product Desig
Integrating Biological Oxidation of Arsenite with Iron Electrocoagulation: A Novel In-line Technique for Enhanced Removal of Arsenite from Water
No full textHuman exposure to the toxic element arsenic due to consumption of arsenic contaminated water is still a global issue worldwide. Conventional treatment techniques are not very efficient at removing arsenite, which is the predominant species of arsenic in raw groundwater. Biological oxidation of arsenite by arsenic oxidizing bacteria (AsOB) has shown potential to effectively oxidize arsenite to arsenate without use of any chemicals. Arsenite is then effectively removed by adsorption or separation technologies. Iron Electrocoagulation (Fe-EC) is also emerging as an influential technique for arsenic removal that involves in-situ generation of iron coagulants using iron electrodes by electrolytic oxidation of anode. The main advantage of Fe-EC is that it does not require dosage of chemical coagulants so can be beneficial to communities with better access to electricity than chemicals.This research work is done to combine the two techniques: biological oxidation of arsenite and Fe-EC, for better removal of arsenite from water. Batch studies on Fe-EC were performed in the laboratory to investigate the effects of charge dosage, charge dosage rate, initial arsenic concentration, arsenic oxidation state and different water matrices on the rate and extent of arsenic removal. Also, growth of AsOB on suitable bio-carrier was performed by continuous dosing of 150 μg/L arsenite-spiked water over a period of 49 days. The AsOB grown on the bio-carriers performed 90 % oxidation of 150 μg/L arsenite after a period of 35 days. Finally, two continuous flow system were developed one containing arsenite oxidation step by AsOB followed by Fe-EC and rapid sand filtration whereas the other contained only Fe-EC and rapid sand filtration. The system containing biological oxidation followed by Fe- EC removed arsenite below the WHO standard (10 μg/L ) from an initial arsenite concentration of 150 μg/L at a low iron dosage compared to the system where only Fe-EC was applied.Environmental Biotechnolog
- …
