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Similar aggregation and β-sheet propensity of amino acids in globular proteins and amyloids, sugg... more Similar aggregation and β-sheet propensity of amino acids in globular proteins and amyloids, suggests comparable principles of their formation. Here we show that during the process of aggregation into amyloid-like fibers, these rules are not the same in an amino-acid-homopolymer (AAHP) polyglutamine (PolyGln). An aggregation kinetic analysis on nine-point mutants of a forty-six long PolyGln peptide was carried in physiological conditions. At the dynamic equilibrium state of aggregation, critical-concentration derived free-energy differences, signifying aggregation propensity of incorporated amino acids were obtained. None of the obtained propensities correlated with existing conventional aggregation and β-sheet propensities of the amino acids in proteins and amyloids. Further, the differential aggregation behavior of all the peptides only correlated with van der Waals volume of the incorporated amino acid and not with any other physicochemical characteristic of amino acids. The new ...
We consider the inference problem of reconstructing a visual stimulus from brain activity measure... more We consider the inference problem of reconstructing a visual stimulus from brain activity measurements (e.g. fMRI) that encode this stimulus. Recovering a complete image is complicated by the fact that neural representations are noisy, high-dimensional, and contain incomplete information about image details. Thus, reconstructions of complex images from brain activity require a strong prior. Here we propose to train generative adversarial networks (GANs) to learn a generative model of images that is conditioned on measurements of brain activity. We consider two challenges of this approach: First, given that GANs require far more data to train than is typically collected in an fMRI experiment, how do we obtain enough samples to train a GAN that is conditioned on brain activity? Secondly, how do we ensure that our generated samples are robust against noise present in fMRI data? Our strategy to surmount both of these problems centers around the creation of surrogate brain activity sampl...
Background. Femoral bone remodeling around hip prosthesis after total hip arthroplasty (THA) is d... more Background. Femoral bone remodeling around hip prosthesis after total hip arthroplasty (THA) is definite but unpredictable in time and place. This study aimed to investigate the implant-specific remodeling and periprosthetic bone mineral density (BMD) changes after implantation of the Ribbed anatomic cementless femoral stem. Methods. After power analysis, 41 patients who had undergone primary unilateral THA with the Ribbed anatomic cementless stem were included. BMD of the seven Gruen zones was measured by dual-energy X-ray absorptiometry, and the contact, fitness, and fixation of the femoral stem and proximal femur were analyzed by X-ray. Additional clinical outcome parameters were also recorded. Results. Compared with the contralateral unoperated side, significant reductions of BMD were detected in the distal zone (Gruen zone 4: 1.665±0.198 versus 1.568±0.242 g/cm2, P=0.001) and middle distal zone (Gruen zone 5: 1.660±0.209 versus 1.608±0.215 g/cm2, P=0.026) on the prosthetic side...
Topological insulators with spin-momentum-locked topological surface states are expected to exhib... more Topological insulators with spin-momentum-locked topological surface states are expected to exhibit a giant spin-orbit torque in the topological insulator/ferromagnet systems. To date, the topological insulator spin-orbit torque-driven magnetization switching is solely reported in a Cr-doped topological insulator at 1.9 K. Here we directly show giant spin-orbit torque-driven magnetization switching in a Bi2Se3/NiFe heterostructure at room temperature captured using a magneto-optic Kerr effect microscope. We identify a large charge-to-spin conversion efficiency of ~1-1.75 in the thin Bi2Se3 films, where the topological surface states are dominant. In addition, we find the current density required for the magnetization switching is extremely low, ~6 × 10(5) A cm(-2), which is one to two orders of magnitude smaller than that with heavy metals. Our demonstration of room temperature magnetization switching of a conventional 3d ferromagnet using Bi2Se3 may lead to potential innovations in...
... On the Reactivity of Metal and Organometallic Halides toward R3 Sn O SnR3 Systems Kiran Singh... more ... On the Reactivity of Metal and Organometallic Halides toward R3 Sn O SnR3 Systems Kiran Singhal, Rahul Mishra, and Prem Raj Department of Chemistry, University of Lucknow, Lucknow 226 007, India Received 12 April 2009; revised 20 June 2009 ...
VopK, a type III effector protein, has been implicated in the pathogenesis of Vibrio cholerae str... more VopK, a type III effector protein, has been implicated in the pathogenesis of Vibrio cholerae strains belonging to diverse serogroups. Ectopic expression of this protein exhibits strong toxicity in yeast model system. In order to map critical residues in VopK, we scanned the primary sequence guided by available data on various toxins and effector proteins. Our in silico analysis of VopK indicated the presence of predicted MCF1-SHE (SHxxxE) serine peptidase domain at the C-terminus region of the protein. Substitution of each of the predicted catalytic triad residues namely Ser314, His353 and Glu357 with alanine resulted in recombinant VopK proteins varying in lethality as evaluated in yeast model system. We observed that replacement of glutamate357 to alanine causes complete loss in toxicity while substitutions of serine314 and histidine353 with alanine exhibited partial loss in toxicity without affecting the stability of variants. In addition, replacement of another conserved serine...
Restoring the antibacterial properties of existing antibiotics is of great concern. Herein, we pr... more Restoring the antibacterial properties of existing antibiotics is of great concern. Herein, we present, for the first time, the formation and deposition of stable antibiotic nanoparticles (NPs) on graphene oxide (GO) sheets by a facile one-step sonochemical technique. Sonochemically synthesized graphene oxide/tetracycline (GO/TET) composite shows enhanced activity against both sensitive and resistant Staphylococcus aureus (S. aureus). The size and deposition of tetracycline (TET) nanoparticles on GO can be controlled by varying the sonication time. The synthesized NPs ranged from 21 to 180 nm. Moreover, ultrasonic irradiation does not cause any structural and chemical changes to the TET molecule as confirmed by Fourier transform infrared spectroscopy (FTIR). The virtue of π-π stacking between GO and TET additionally facilitate the coating of TET NPs upon GO. A time dependent release kinetics of TET NPs from the GO surface is also monitored providing important insights regarding the mechanism of antibacterial activity of GO/TET composites. Our results show that the GO/TET composite is bactericidal in nature, resulting in similar values of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). This composite is found to be active against TET resistant S. aureus at a concentration four times lower than the pristine TET. The sensitive S. aureus follows the same trend showing six times lower MIC values compared to pristine TET. GO shows no activity against both sensitive and resistant S. aureus even at a concentration as high as 1 mg/mL but influences the biocidal activity of the GO/TET composite. We propose that the unique structure and composition manifested by GO/TET composites may be further utilized for different formulations of antibiotics with GO. The sonochemical method used in this work can be precisely tailored for the stable deposition of a variety of antibiotics on the GO surface to reduce health risks and increase the spectrum of applications.
Similar aggregation and β-sheet propensity of amino acids in globular proteins and amyloids, sugg... more Similar aggregation and β-sheet propensity of amino acids in globular proteins and amyloids, suggests comparable principles of their formation. Here we show that during the process of aggregation into amyloid-like fibers, these rules are not the same in an amino-acid-homopolymer (AAHP) polyglutamine (PolyGln). An aggregation kinetic analysis on nine-point mutants of a forty-six long PolyGln peptide was carried in physiological conditions. At the dynamic equilibrium state of aggregation, critical-concentration derived free-energy differences, signifying aggregation propensity of incorporated amino acids were obtained. None of the obtained propensities correlated with existing conventional aggregation and β-sheet propensities of the amino acids in proteins and amyloids. Further, the differential aggregation behavior of all the peptides only correlated with van der Waals volume of the incorporated amino acid and not with any other physicochemical characteristic of amino acids. The new ...
We consider the inference problem of reconstructing a visual stimulus from brain activity measure... more We consider the inference problem of reconstructing a visual stimulus from brain activity measurements (e.g. fMRI) that encode this stimulus. Recovering a complete image is complicated by the fact that neural representations are noisy, high-dimensional, and contain incomplete information about image details. Thus, reconstructions of complex images from brain activity require a strong prior. Here we propose to train generative adversarial networks (GANs) to learn a generative model of images that is conditioned on measurements of brain activity. We consider two challenges of this approach: First, given that GANs require far more data to train than is typically collected in an fMRI experiment, how do we obtain enough samples to train a GAN that is conditioned on brain activity? Secondly, how do we ensure that our generated samples are robust against noise present in fMRI data? Our strategy to surmount both of these problems centers around the creation of surrogate brain activity sampl...
Background. Femoral bone remodeling around hip prosthesis after total hip arthroplasty (THA) is d... more Background. Femoral bone remodeling around hip prosthesis after total hip arthroplasty (THA) is definite but unpredictable in time and place. This study aimed to investigate the implant-specific remodeling and periprosthetic bone mineral density (BMD) changes after implantation of the Ribbed anatomic cementless femoral stem. Methods. After power analysis, 41 patients who had undergone primary unilateral THA with the Ribbed anatomic cementless stem were included. BMD of the seven Gruen zones was measured by dual-energy X-ray absorptiometry, and the contact, fitness, and fixation of the femoral stem and proximal femur were analyzed by X-ray. Additional clinical outcome parameters were also recorded. Results. Compared with the contralateral unoperated side, significant reductions of BMD were detected in the distal zone (Gruen zone 4: 1.665±0.198 versus 1.568±0.242 g/cm2, P=0.001) and middle distal zone (Gruen zone 5: 1.660±0.209 versus 1.608±0.215 g/cm2, P=0.026) on the prosthetic side...
Topological insulators with spin-momentum-locked topological surface states are expected to exhib... more Topological insulators with spin-momentum-locked topological surface states are expected to exhibit a giant spin-orbit torque in the topological insulator/ferromagnet systems. To date, the topological insulator spin-orbit torque-driven magnetization switching is solely reported in a Cr-doped topological insulator at 1.9 K. Here we directly show giant spin-orbit torque-driven magnetization switching in a Bi2Se3/NiFe heterostructure at room temperature captured using a magneto-optic Kerr effect microscope. We identify a large charge-to-spin conversion efficiency of ~1-1.75 in the thin Bi2Se3 films, where the topological surface states are dominant. In addition, we find the current density required for the magnetization switching is extremely low, ~6 × 10(5) A cm(-2), which is one to two orders of magnitude smaller than that with heavy metals. Our demonstration of room temperature magnetization switching of a conventional 3d ferromagnet using Bi2Se3 may lead to potential innovations in...
... On the Reactivity of Metal and Organometallic Halides toward R3 Sn O SnR3 Systems Kiran Singh... more ... On the Reactivity of Metal and Organometallic Halides toward R3 Sn O SnR3 Systems Kiran Singhal, Rahul Mishra, and Prem Raj Department of Chemistry, University of Lucknow, Lucknow 226 007, India Received 12 April 2009; revised 20 June 2009 ...
VopK, a type III effector protein, has been implicated in the pathogenesis of Vibrio cholerae str... more VopK, a type III effector protein, has been implicated in the pathogenesis of Vibrio cholerae strains belonging to diverse serogroups. Ectopic expression of this protein exhibits strong toxicity in yeast model system. In order to map critical residues in VopK, we scanned the primary sequence guided by available data on various toxins and effector proteins. Our in silico analysis of VopK indicated the presence of predicted MCF1-SHE (SHxxxE) serine peptidase domain at the C-terminus region of the protein. Substitution of each of the predicted catalytic triad residues namely Ser314, His353 and Glu357 with alanine resulted in recombinant VopK proteins varying in lethality as evaluated in yeast model system. We observed that replacement of glutamate357 to alanine causes complete loss in toxicity while substitutions of serine314 and histidine353 with alanine exhibited partial loss in toxicity without affecting the stability of variants. In addition, replacement of another conserved serine...
Restoring the antibacterial properties of existing antibiotics is of great concern. Herein, we pr... more Restoring the antibacterial properties of existing antibiotics is of great concern. Herein, we present, for the first time, the formation and deposition of stable antibiotic nanoparticles (NPs) on graphene oxide (GO) sheets by a facile one-step sonochemical technique. Sonochemically synthesized graphene oxide/tetracycline (GO/TET) composite shows enhanced activity against both sensitive and resistant Staphylococcus aureus (S. aureus). The size and deposition of tetracycline (TET) nanoparticles on GO can be controlled by varying the sonication time. The synthesized NPs ranged from 21 to 180 nm. Moreover, ultrasonic irradiation does not cause any structural and chemical changes to the TET molecule as confirmed by Fourier transform infrared spectroscopy (FTIR). The virtue of π-π stacking between GO and TET additionally facilitate the coating of TET NPs upon GO. A time dependent release kinetics of TET NPs from the GO surface is also monitored providing important insights regarding the mechanism of antibacterial activity of GO/TET composites. Our results show that the GO/TET composite is bactericidal in nature, resulting in similar values of minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). This composite is found to be active against TET resistant S. aureus at a concentration four times lower than the pristine TET. The sensitive S. aureus follows the same trend showing six times lower MIC values compared to pristine TET. GO shows no activity against both sensitive and resistant S. aureus even at a concentration as high as 1 mg/mL but influences the biocidal activity of the GO/TET composite. We propose that the unique structure and composition manifested by GO/TET composites may be further utilized for different formulations of antibiotics with GO. The sonochemical method used in this work can be precisely tailored for the stable deposition of a variety of antibiotics on the GO surface to reduce health risks and increase the spectrum of applications.
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Papers by Rahul Mishra