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Stereoselective Addition of a Lithium Anion of 1,1-Diphenyl-2-aza-pentadiene to Sulfinimines: Application to the Synthesis of (-)-Epiquinamide
No full textThe addition of a lithium anion of diphenylallylimine to nonracemic sulfinimines was investigated. It was found that the reaction with sulfinimines derived from aliphatic aldehydes afforded the products with excellent diastereoselectivity (>99:1), furnishing the product vicinal diamines in very good yields. Application of the formed product vicinal diamines was demonstrated in the total synthesis of the natural product (-)-epiquinamide
A constitutive model for block-copolymers based on effective temperature
No full textPhase segregated copolymers such as elastomeric copolymers find myriad applications especially in impact resistant structures. When domains with varying relaxation characteristics are present, these polymers exhibit thermorheologically complex behaviour. The multiple relaxation processes are herein captured using the effective temperature based thermodynamics, used extensively in modelling thermo-mechanical response of metals and polymers. Specifically, we use two slowly evolving configurational subsystems and a fast evolving kinetic-vibration (K-V) subsystem. The two configurational subsystems represent the inter-molecular and intra-molecular meso-scale configurational transformations occurring within the two domains. The K-V subsystem represents the faster atomic vibrations. The configurational subsystems are weakly coupled with the K-V through heat exchange which accounts for structural relaxations of the individual domains towards the equilibrium microstructure. Based on this, we are able to capture strain rate dependence and strain induced softening of these materials under cyclic loads. In comparison with the existing formulations for such copolymers, ours is perhaps a more transparent approach, as it uses quantities such as volume fraction, glass transition temperatures of individual domains as material parameters. Indeed, our formulation could be readily adapted for non-elastomeric copolymers. It should also be potentially useful as a design tool for copolymers with increased glass transition range
Exploring the functional and corrosion behavior of friction stir welded NiTi shape memory alloy
No full textThe friction stir welding was proved to be a promising process to weld NiTi shape memory alloy with adequate mechanical strength and retention of shape memory effect. In this work, the tool wear during welding and the compositional change in the weld cross section has been evaluated. The tensile cyclic behavior for different strain percentages has been investigated. Interestingly, the thermomechanical behavior of the weld was studied using electrical actuation. The actuation was carried out at different current and the actuation temperatures were corroborated with phase transformation temperature range measured using differential scanning calorimetry. A maximum displacement of 17.8 mm was recorded at the actuation current of 5 A. The electrochemical corrosion testing has been performed to understand the corrosion behavior of the friction stir welded NiTi. The weld has exhibited a lower corrosion resistance than the base metal as seen from the lower breakdown potential of 250 mV and a higher current density of 1.5 x 10(-4) mA/cm(2)
Phenotypic Switching of Naïve T Cells to Immune-Suppressive Treg-Like Cells by Mutant KRAS
No full textOncogenic (mutant) Ras protein Kirsten rat sarcoma viral oncogene homolog (KRAS) promotes uncontrolled proliferation, altered metabolism, and loss of genome integrity in a cell-intrinsic manner. Here, we demonstrate that CD4(+) T cells when incubated with tumor-derived exosomes from mutant (MT) KRAS non-small-cell lung cancer (NSCLC) cells, patient sera, or a mouse xenograft model, induce phenotypic conversion to FOXP3(+) Treg-like cells that are immune-suppressive. Furthermore, transfecting T cells with MT KRAS cDNA alone induced phenotypic switching and mathematical modeling supported this conclusion. Single-cell sequencing identified the interferon pathway as the mechanism underlying the phenotypic switch. These observations highlight a novel cytokine-independent, cell-extrinsic role for KRAS in T cell phenotypic switching. Thus, targeting this new class of Tregs represents a unique therapeutic approach for NSCLC. Since KRAS is the most frequently mutated oncogene in a wide variety of cancers, the findings of this investigation are likely to be of broad interest and have a large scientific impact
Diversification in the mountains: a generic reappraisal of the Western Ghats endemic gecko genus Dravidogecko Smith, 1933 (Squamata: Gekkonidae) with descriptions of six new species
No full textThe monotypic genus Dravidogecko, represented by its type-species D. anamallensis, is singular amongst peninsular Indian gekkonid lineages in its endemism to the Western Ghats. Molecular species delimitation approaches reveal at least seven species-level lineages within the genus from its distribution range across the mid-high elevations of the southern Western Ghats of India. These lineages, albeit superficially cryptic, are patently diagnosable from each other by employing a limited but precise set of morphological characters. Six of these lineages that were obscured under the nomen D. anamallensis are herein recognized as distinct species. A reappraisal of the genus Dravidogecko is provided based on external morphology and osteological characters, along with a detailed redescription of the holotype of D. anamallensis. A key to the species based on diagnostic characters is presented. Gene-trees based on mitochondrial and nuclear DNA data recovered marginally disparate topologies and were consequently coalesced into a species-tree for phylogenetic inference. Timetree analysis reveals late Miocene cladogenesis in this group and establishes late Palaeocene divergence from its sister genus, Hemidactylus, making Dravidogecko one of the earliest, extant lizard lineages to have colonized peninsular India
Estimating Pilots' Cognitive Load From Ocular Parameters Through Simulation and In-Flight Studies
No full textEye tracking is the process of measuring either the point of gaze (where one is looking) or the motion of an eye relative to the head. This paper investigated use of eye gaze trackers in military aviation environment to automatically estimate pilot's cognitive load from ocular parameters. In the first study, we used a fixed base variable stability flight simulator with longitudinal tracking task and collected data from 14 military pilots. In a second study, we undertook four test flights with BAES Hawk Trainer and Jaguar aircrafts doing air to ground attack training missions and constant G level turn maneuvers up to +5G. Our study found that ocular parameters like rate of fixation is significantly different in different flying conditions. It also significantly correlated with rate of descent during air to ground dive training task, normal load factor (G) of the aircraft during constant G level turn maneuvers and pilot's control inceptor and tracking error in simulation tasks. Results from our studies can be used for real time estimation of pilots' cognitive load, providing suitable warnings and alerts to the pilot in cockpit and training of military pilots on cognitive load management during operational missions
Anomalous lattice contraction and emergent electronic phases in Bi-doped Eu2Ir2O7
No full textWe study the pyrochlore series (Eu1-xBix)(2)Ir2O7 for 0 <= x <= 1. We show that for small x, the lattice undergoes an anomalous contraction but the time reversal symmetry breaking all-in/all-out state remains robust and the resistivity approaches a 1/T dependence at low T, suggesting proximity to the Weyl semimetallic phase. At the boundary near 10% Bi doping, a qualitatively different ground state emerges, which is characterized by a metallic behavior and the absence of magnetic ordering at least down to 0.02 K. For higher Bi doping, the resistivity remains metallic, and evolves gradually from T linear to T-2 to T-3/2, suggesting the possibilities of myriad different electronic phases between Eu2Ir2O7 and Bi2Ir2O7
Statistics of heat transport across a capacitively coupled double quantum dot circuit
No full textWe study heat current and the full statistics of heat fluctuations in a capacitively coupled double quantum dot system. This work is motivated by recent theoretical studies and experimental works on heat currents in quantum dot circuits. As expected intuitively, within the (static) mean-field approximation, the system at steady state decouples into two single-dot equilibrium systems with renormalized dot energies, leading to zero average heat flux and fluctuations. This reveals that dynamic correlations induced between electrons on the dots are solely responsible for the heat transport between the two reservoirs. To study heat current fluctuations, we compute the steady-state cumulant generating function for heat exchanged between reservoirs using two approaches: the Lindblad quantum master equation approach, which is valid for arbitrary Coulomb interaction strength but weak system-reservoir coupling strength, and the saddle point approximation for the Schwinger-Keldysh coherent-state path integral, which is valid for arbitrary system-reservoir coupling strength but weak Coulomb interaction strength. Using thus obtained generating functions, we verify the steady-state fluctuation theorem for stochastic heat flux and study the average heat current and its fluctuations. We find that the heat current and its fluctuations change nonmonotonically with the Coulomb interaction strength (U) and system-reservoir coupling strength (Gamma) and are suppressed for large values of U and Gamma
A Composite of Hyaluronic Acid-Modified Graphene Oxide and Iron Oxide Nanoparticles for Targeted Drug Delivery and Magnetothermal Therapy
No full textGraphene oxide (GO) nanoparticles have been developed for a variety of biomedical applications as a number of different therapeutic modalities may be added onto them. Here, we report the development and testing of such a multifunctional GO nanoparticle platform that contains a grafted cell-targeting functionality, active pharmaceutical ingredients, and particulates that enable the use of magnetothermal therapy. Specifically, we demonstrate the ability to covalently attach hyaluronic acid (HA) onto GO, and the resultant nanoparticulates (GO-HA) exhibited low inherent toxicity toward two different breast cancer cell lines, BT-474 and MDA-MB-231. Doxorubicin (Dox) and paclitaxel (Ptx) were successfully loaded onto GO-HA with high and moderate efficiencies, respectively. A GO-HA-Dox/Ptx system was significantly better than the GO-Dox/Ptx system at specifically killing CD44-expressing MDA-MB-231 cells but not BT-474 cells that do not express CD44. Further, modified iron oxide nanoparticles were loaded onto the GO-HA-Dox system, enabling the use of magnetic hyperthermia. Hyperthermia in combination with Dox treatment through the GO-HA system showed significantly better performance in reducing viable tumor cell numbers when compared to the individual systems. In summary, we showcase a multifunctional GO nanoparticle system that demonstrates improved efficacy in killing tumor cells
From Quantum Chemistry to Networks in Biology: A Graph Spectral Approach to Protein Structure Analyses
No full textIn this perspective article, we present a multi-disciplinary approach for characterizing protein structure networks. We first place our approach in its historical context and describe the manner in which it synthesizes concepts from quantum chemistry, biology of polymer conformations, matrix mathematics, and percolation theory. We then explicitly provide the method for constructing the protein structure network in terms of non-covalently interacting amino acid side chains and show how a mine of information can be obtained from the graph spectra of these networks. Employing suitable mathematical approaches, such as the use of a weighted, Laplacian matrix to generate the spectra, enables us to develop rigorous methods for network comparison and to identify crucial nodes responsible for the network integrity through a perturbation approach. Our scoring methods have several applications in structural biology that are elusive to conventional methods of analyses. Here, we discuss the instances of (a) protein structure comparison that includes the details of side chain connectivity, (b) contribution to node clustering as a function of bound ligand, explaining the global effect of local changes in phenomena such as allostery, and (c) identification of crucial amino acids for structural integrity, derived purely from the spectra of the graph. We demonstrate how our method enables us to obtain valuable information on key proteins involved in cellular functions and diseases such as GPCR and HIV protease and discuss the biological implications. We then briefly describe how concepts from percolation theory further augment our analyses. In our concluding perspective for future developments, we suggest a further unifying approach to protein structure analyses and a judicious choice of questions to employ our methods for larger, more complex networks, such as metabolic and disease networks