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Disassociation of beta 1-alpha 1-beta 2 from the alpha 2-alpha 3 domain of prion protein (PrP) is a prerequisite for the conformational conversion of PrPC into PrPSc: Driven by the free energy landscape
No full textMisfolding of the cellular prion protein (PrPC) into beta-sheet-rich scrapie form (PrPSC) is associated with transmissible spongiform encephalopathies. A point mutation F198S is responsible for the development of a rare inherited Gerstmann-Straussler-Scheinker disease caused by the aggregation of PrPC. Thus, identification and the structural characterization of aggregation-prone regions are essential to delineate the conversion of PrPC to the disease-associated PrPSc upon F198S mutation. In the present study, molecular dynamics simulations on the wild-type PrP (WT-PrP) and its mutant were performed to explore the structural basis responsible for aggregation driven by the mutation. Secondary structure analysis revealed that the mutant exhibited a partial unfolding on alpha 2 and the complete distortion in the 3(10)-helix of the beta 2-beta 2 loop. Remarkably, the beta 2-alpha 2 loop is in proximity to alpha 3 attributed by the long-range hydrophobic interactions and such structural intimacy is not observed in the WT-PrP. Owing to this, the beta 1-alpha 1-beta 2 regions have separated from alpha 2-alpha 3 domain resulting in the impairment on the hydrogen bond between alpha 1 and alpha 3. Thus, the present study provides a detailed structural description of the F198S mutant in line with previous experimental results and delivers insights into the structural basis responsible for the conversion of PrPC to the disease-associated PrPSc
Efficient ab initio plus analytic calculation of the effect of GaN layer tensile strain in AlGaN/GaN heterostructures
No full textWe have addressed the existing ambiguity regarding the effect of tensile strain in the underlying GaN layer on AlxGa1-xN/GaN heterostructure properties. The bandgaps and band-offsets for AlxGa1-xN on strained GaN were first computed using density functional theory (DFT), in the generalized gradient approximations (GGA) and hybrid functional Gaussian-Perdew-Burke-Ernzerhof (Gau-PBE) regimes. We propose a simple model to relate the GGA and Gau-PBE bandgaps, which is used to determine the realistic bandgaps of strained AlGaN. The bandgaps and band-offsets from the DFT calculations are then used to analytically calculate the two-dimensional electron gas density in an AlxGa1-xN/GaN hetero-interface. Our bandstructure calculations show that it is not possible to induce significant change in band-offsets through strain in the GaN layer. The charge-density calculations indicate that such strain can, however, modulate the polarization charge and thereby enhance the 2DEG density at the AlGaN/GaN interface substantially
Subjective and Objective Quality Assessment of Stitched Images for Virtual Reality
No full textWe consider the problem of quality assessment (QA) of image stitching algorithms used to generate panoramic images for virtual reality applications. Our contributions are twofold. We design the Indian Institute of Science Stitched Image QA (ISIQA) database consisting of 264 stitched images and 6600 human quality ratings. The database consists of a variety of artifacts clue to stitching such as blur, ghosting, photometric, and geometric distortions. We then devise an objective QA model called the stitched image quality evaluator (SIQE) using the statistics of steerable pyramid decompositions. In particular, we propose a Gaussian mixture model to capture the bivariate statistics of neighboring coefficients of steerable pyramid decompositions and show this to he effective in modeling the increased spatial correlation due to ghosting artifacts. We show through extensive experiments that our quality model correlates very well with subjective scores in the ISIQA database. The ISIQA database as well as the software release of SIQE has been made available online for public use and evaluation purposes
Large electromechanical response in ferroelectrics: Beyond the morphotropic phase boundary paradigm
No full textFerroelectric based piezoceramics exhibiting large electromechanical response are used as sensors, actuators, and transducers in wide-ranging applications spanning sectors like space, defense, medical diagnostics, etc. In general, the large piezoelectric response in ferroelectric solid solutions is associated with a composition driven interferroelectric instability, commonly known as a morphotropic phase boundary (MPB). Here, we show that MPB is not necessarily required to achieve electromechanical response equivalent to, or even more than what can be achieved in MPB based ferroelectric solid solutions. We show this on two ferroelectric solid solution systems, namely, (1-x)PbTiO3-(x)Bi(Ni1/2Hf1/2 )O-3 (PT-BNH) and (Bi, La)FeO3 -PbTiO3 (BF-PT:La) which show large piezoelectric response (d(33) similar to 450 pC/N) and extraordinarily high electrostrain of similar to 1.3%, respectively. Although analogous to the conventional MPB systems, the critical compositions of these two alloys mimic a two-phase structural state (cubic + tetragonal), detailed analysis that suggests that it is not so. The cubic phase is rather a manifestation of short correlation length of the tetragonal regions and appears when the system is compositionally driven from a normal ferroelectric state to a relaxor ferroelectric state. This proves that, in contrast to conventional MPB systems, the large electromechanical response of the critical compositions of PT-BNH and BF-PT:La is not due to interferroelectric instability enabled polarization rotation. In the absence of the MPB, the sole contributor to large electromechanical response is a process associated with domain wall motion, large local polarization, and (non-MPB) lattice softening. The generalized ideas derived from our investigation offer scope for expanding the basket of high-performance piezoelectric materials by exploring solid solutions outside of the MPB framework
Cyanogenic glycosides: A sustainable carbon and nitrogen source for developing resilient Janus reversible oxygen electrocatalysts for metal-air batteries
No full textMost of the transition metal based heteroatom doped carbon electrocatalysts, utilizes the fossil fuel derived commercially available precursors as source of nitrogen and carbon which may question our environmental generosity. Herein, we have developed Ni-based efficient bifunctional electrocatalysts using apple seeds (that contains cyanogenic glycosides) as the precursor for nitrogen and carbon. With tuning the temperature, we were able to optimize the nitrogen doping up to similar to 3 at.%. The optimized electrocatalyst catalyses the oxygen reduction reaction (ORR) process with muted peroxide generation (for 0.750-0.1 V the % HO2- generation similar to 3 - 2%), preferential 4e(-) reduction pathways (n similar to 3.93 to 3.98 in 0.75-0.1 V range) and electron transfer via inner-sphere electron transfer mechanism which ensures the maximum utilization of instituted active centres owing to the direct interaction of reactant species. Alike to ORR, the superior oxygen evolution reaction (OER) performance with smaller E-onset, E-J =10, Tafel slope and enduring accelerated stability test advocates its potential as a bifunctional oxygen electrocatalyst. Moreover, smaller potential gap Delta E (E-J10_(OER) - E-1/2_(ORR)) of 0.845 V further warrants the energy efficient OER/ORR process. A porotype of Al-air battery system using our catalysts as oxygen electrode and chocolate wafer as anode material is well capable of powering the light emitting diodes. This study hopefully opens a new avenue to explore cyanogenic glycosides plants product to develop multifunctional electrocatalysts
Investigation of anti-cancer and migrastatic properties of novel curcumin derivatives on breast and ovarian cancer cell lines
No full textBackground Curcumin is known for its multitude of medicinal properties, including anti-cancer and migrastatic activity. Efforts to overcome poor bioavailability, stability, and side effects associated with the higher dose of curcumin has led to the development of newer derivatives of curcumin. Thus, the focus of this study is to screen novel curcumin derivatives, namely ST03 and ST08, which have not been reported before, for their cytotoxicity and migrastatic property on cancer cells. Methods Anti-cancer activity of ST03 and ST08 was carried out using standard cytotoxicity assays viz., LDH, MTT, and Trypan blue on both solid and liquid cancer types. Flow cytometric assays and western blotting was used to investigate the cell death mechanisms. Transwell migration assay was carried out to check for migrastatic properties of the compounds. Results Both the compounds, ST03 and ST08, showed similar to 100 fold higher potency on liquid and solid tumour cell lines compared to its parent compound curcumin. They induced cytotoxicity by activating the intrinsic pathway of apoptosis in the breast (MDA-MB-231) and ovarian cancer cell lines (PA-1) bearing metastatic and stem cell properties, respectively. Moreover, ST08 also showed inhibition on breast cancer cell migration by inhibiting MMP1 (matrix metalloproteinase 1). Conclusion Both ST03 and ST08 exhibit anti-cancer activity at nanomolar concentration. They induce cell death by activating the intrinsic pathway of apoptosis. Also, they inhibit migration of the cancer cells by inhibiting MMP1 in breast cancer cells
Assessing the performance of in silico methods for predicting the pathogenicity of variants in the gene CHEK2, among Hispanic females with breast cancer
No full textThe availability of disease-specific genomic data is critical for developing new computational methods that predict the pathogenicity of human variants and advance the field of precision medicine. However, the lack of gold standards to properly train and benchmark such methods is one of the greatest challenges in the field. In response to this challenge, the scientific community is invited to participate in the Critical Assessment for Genome Interpretation (CAGI), where unpublished disease variants are available for classification by in silico methods. As part of the CAGI-5 challenge, we evaluated the performance of 18 submissions and three additional methods in predicting the pathogenicity of single nucleotide variants (SNVs) in checkpoint kinase 2 (CHEK2) for cases of breast cancer in Hispanic females. As part of the assessment, the efficacy of the analysis method and the setup of the challenge were also considered. The results indicated that though the challenge could benefit from additional participant data, the combined generalized linear model analysis and odds of pathogenicity analysis provided a framework to evaluate the methods submitted for SNV pathogenicity identification and for comparison to other available methods. The outcome of this challenge and the approaches used can help guide further advancements in identifying SNV-disease relationships
The DNA walk and its demonstration of deterministic chaos-relevance to genomic alterations in lung cancer
No full textMotivation: Advancements in cancer genetics have facilitated the development of therapies with actionable mutations. Although mutated genes have been studied extensively, their chaotic behavior has not been appreciated. Thus, in contrast to naive DNA, mutated DNA sequences can display characteristics of unpredictability and sensitivity to the initial conditions that may be dictated by the environment, expression patterns and presence of other genomic alterations. Employing a DNA walk as a form of 2D analysis of the nucleotide sequence, we demonstrate that chaotic behavior in the sequence of a mutated gene can be predicted. Results: Using fractal analysis for these DNA walks, we have determined the complexity and nucleotide variance of commonly observed mutated genes in non-small cell lung cancer, and their wild-type counterparts. DNA walks for wild-type genes demonstrate varying levels of chaos, with BRAF, NTRK1 and MET exhibiting greater levels of chaos than KRAS, paxillin and EGFR. Analyzing changes in chaotic properties, such as changes in periodicity and linearity, reveal that while deletion mutations indicate a notable disruption in fractal `self-similarity', fusion mutations demonstrate bifurcations between the two genes. Our results suggest that the fractals generated by DNA walks can yield important insights into potential consequences of these mutated genes
Longitudinal wave propagation in one-dimensional waveguides with sinusoidally varying depth
No full textIn this paper, longitudinal elastic wave propagation in one-dimensional waveguides with sinusoidally varying depth is investigated. Furthermore, different types of such waveguide designs are explored to understand their capability to attenuate the group speeds as well as the velocity amplitudes. The plane waveguide configurations with sinusoidally varying depth, of three types, namely Convex, Concave and Full, along with their combinations and variants, whose segmental depth along the length of the waveguide is modeled by a sine function having an amplitude parameter alpha and the half-period p, which leads to a governing differential equation with variable coefficients, are considered in this study. To study the longitudinal wave propagation in these inhomogenous waveguides, a novel superconvergent finite element formulation is developed, which gives an exact stiffness matrix. In addition to the wave propagation analysis, static and free vibration behaviors in these waveguides are also studied. The implemented superconvergent finite element formulation for these studies is validated with the commercial finite element software Abaqus. In the first part of the wave propagation analysis, abilities of the three plane waveguide configurations with sinusoidally varying depth to attenuate high amplitude and frequency waves are investigated for different values of alpha. Next, four different waveguides composed of Convex-Concave combinations are studied with an aim to get better attenuation. Following this, the waveguides' segmental parameters, alpha and p, are varied across the segments along the length of the waveguide, using a sine function and polynomial power law to see if such graded variations give better energy absorption properties compared to the plane waveguides whose parameters are unvarying. In the last part, a developed inhomogenous rod of a certain length is inserted in the middle of a uniform waveguide to study the possibility of changing the longitudinal wave propagation characteristics of the uniform waveguide. The results from the analyses show that the group speed and amplitude of the longitudinal wave in these configurations change significantly with space as well as with frequencies, especially for high values of alpha. The Concave and Full waveguides delay the propagation of longitudinal waves significantly, which translates into the reflected waves appearing later in the chosen large time window. The Convex waveguide and its variants reduce the wave amplitudes significantly. Building on these results, some waveguides with notable attenuation characteristics are proposed
Impact of Continental Freshwater Runoff on Coastal Sea Level
No full textFreshwater discharge to the coastal ocean is a fundamental component of the global water cycle. It can impact coastal sea level over a broad range of spatial and temporal scales. Here we review the status of the current knowledge based on observational and modeling approaches. The main limitation in studies of the influence of rivers on coastal sea level has been the lack of consolidated discharge databases. We first provide an inventory of the main data sources currently available. We then review the existing knowledge about the runoff forcing of coastal sea level, differentiating between the mass and steric height contributions. Both mechanisms are important for coastal sea level budget, although they act on different scales. The mass contribution is related to a global ocean response that is established on relatively short timescales through barotropic processes while the steric contribution is associated with more of a regional adjustment that takes place on longer timescales by means of baroclinic dynamics. While numerical models required to simulate the runoff impact on coastal sea level variability have been improving over the past decades, a similar evolution is awaited for observational techniques, both for in situ observation and for remote sensing