COA6 facilitates cytochrome c oxidase biogenesis as thiol-reductase for copper metallochaperones in mitochondria.

The mitochondrial cytochrome c oxidase, the terminal enzyme of the respiratory chain, contains heme and copper centers for electron transfer. The conserved COX2 subunit contains the CuA site, a binuclear copper center. The copper chaperones SCO1, SCO2, and COA6 are required for CuA center formation. Loss of function of these chaperones and the concomitant cytochrome c oxidase deficiency cause severe human disorders. Here we analyzed the molecular function of COA6 and the consequences of COA6 deficiency for mitochondria. Our analyses show that loss of COA6 causes combined complex I and complex IV deficiency and impacts membrane potential driven protein transport across the inner membrane. We demonstrate that COA6 acts as a thiol-reductase to reduce disulphide bridges of critical cysteine residues in SCO1 and SCO2. Cysteines within the CX3CXNH domain of SCO2 mediate its interaction with COA6 but are dispensable for SCO2-SCO1 interaction. Our analyses define COA6 as thiol-reductase, which is essential for CuA biogenesis

Statistical Isotropy violation of the CMB brightness fluctuations

Certain anomalies at large angular scales in the cosmic microwave background measured by WMAP have been suggested as possible evidence of breakdown of statistical isotropy(SI). Most CMB photons free-stream to the present from the surface of last scattering. It is thus reasonable to expect statistical isotropy violation in the CMB photon distribution observed now to have originated from SI violation in the baryon-photon fluid at last scattering, in addition to anisotropy of the primordial power spectrum studied earlier in literature. We consider the generalized anisotropic brightness distribution fluctuations, $\Delta(\vec{k}, \hat{n}, \tau)$ (at conformal time $\tau$) in contrast to the SI case where it is simply a function of $|\vec{k}|$ and $\hat{k} \cdot \hat{n}$. The brightness fluctuations expanded in Bipolar Spherical Harmonic (BipoSH) series, can then be written as $\Delta_{\ell_1 \ell_2}^{L M}(\vec{k}, \tau)$ where $L > 0$ terms encode deviations from statistical isotropy. We study the evolution of $\Delta_{\ell_1 \ell_2}^{L M}(\vec{k}, \tau)$ from non-zero terms $\Delta_{\ell_3 \ell_4}^{L M}(\vec{k}, \tau_s)$ at last scattering. Similar to the SI case, power at small spherical harmonic (SH) multipoles of $\Delta_{\ell_3 \ell_4}^{L M}(\vec{k},\tau_s)$ at the last scattering, is transferred to $\Delta_{\ell_1 \ell_2}^{L M}(\vec{k}, \tau)$ at larger SH multipoles. The structural similarity is more apparent in the asymptotic expression for large values of the final SH multipoles. This formalism allows an elegant identification of any SI violation observed today to a possible origin in the SI violation present in the baryon-photon fluid (eg., due to the presence of significant magnetic field).Comment: 14 pages, 4 figures, added illustrative example of SI violation in baryon-photon fluid, matches version accepted for publication in Phys. Rev.

Study of Kalman, Extended Kalman and Unscented Kalman Filter (An Approach to Design a Power System)

The accurate measurement of harmonics level is essential for designing harmonic filters,monitoring the stress to which the power system devices are subjected due to harmonics and specifying digital filtering techniques for phasor measurements for relaying. This project presents an integrated approach to design an optimal estimator of harmonic components of a power network in the presence of frequency variations. This has led to the study of Kalman, Extended Kalman and Unscented Kalman filter characteristics and a subsequent implementation of the study to design the optimal filter. We have employed the Extended Kalman filter and Unscented Kalman filter algorithms to estimate the power system voltage magnitude in the presence of random noise and distortions again taking into account the measurement noise. Kalman filter being an optimal estimator track the signal corrupted with noise and bearing harmonic distortion quite accurately. Adaptive tracking of harmonic components of a power system can easily be done using these algorithm. The proposed approaches are tested for only static signals. For a test signal both EKF and UKF algorithms are used and the results are compared

Generalized Fisher matrices

16.04.15 KB Ok to add accepted version to spira

Leveraging Local Patch Differences in Multi-Object Scenes for Generative Adversarial Attacks

State-of-the-art generative model-based attacks against image classifiers overwhelmingly focus on single-object (i.e., single dominant object) images. Different from such settings, we tackle a more practical problem of generating adversarial perturbations using multi-object (i.e., multiple dominant objects) images as they are representative of most real-world scenes. Our goal is to design an attack strategy that can learn from such natural scenes by leveraging the local patch differences that occur inherently in such images (e.g. difference between the local patch on the object `person' and the object `bike' in a traffic scene). Our key idea is to misclassify an adversarial multi-object image by confusing the victim classifier for each local patch in the image. Based on this, we propose a novel generative attack (called Local Patch Difference or LPD-Attack) where a novel contrastive loss function uses the aforesaid local differences in feature space of multi-object scenes to optimize the perturbation generator. Through various experiments across diverse victim convolutional neural networks, we show that our approach outperforms baseline generative attacks with highly transferable perturbations when evaluated under different white-box and black-box settings.Comment: Accepted at WACV 2023 (Round 1), camera-ready versio

Overexpression of branched-chain amino acid aminotransferases rescues the growth defects of cells lacking the Barth syndrome-related gene TAZ1.

The yeast protein Taz1 is the orthologue of human Tafazzin, a phospholipid acyltransferase involved in cardiolipin (CL) remodeling via a monolyso CL (MLCL) intermediate. Mutations in Tafazzin lead to Barth syndrome (BTHS), a metabolic and neuromuscular disorder that primarily affects the heart, muscles, and immune system. Similar to observations in fibroblasts and platelets from patients with BTHS or from animal models, abolishing yeast Taz1 results in decreased total CL amounts, increased levels of MLCL, and mitochondrial dysfunction. However, the biochemical mechanisms underlying the mitochondrial dysfunction in BTHS remain unclear. To better understand the pathomechanism of BTHS, we searched for multi-copy suppressors of the taz1Δ growth defect in yeast cells. We identified the branched-chain amino acid transaminases (BCATs) Bat1 and Bat2 as such suppressors. Similarly, overexpression of the mitochondrial isoform BCAT2 in mammalian cells lacking TAZ improves their growth. Elevated levels of Bat1 or Bat2 did not restore the reduced membrane potential, altered stability of respiratory complexes, or the defective accumulation of MLCL species in yeast taz1Δ cells. Importantly, supplying yeast or mammalian cells lacking TAZ1 with certain amino acids restored their growth behavior. Hence, our findings suggest that the metabolism of amino acids has an important and disease-relevant role in cells lacking Taz1 function. KEY MESSAGES: Bat1 and Bat2 are multi-copy suppressors of retarded growth of taz1Δ yeast cells. Overexpression of Bat1/2 in taz1Δ cells does not rescue known mitochondrial defects. Supplementation of amino acids enhances growth of cells lacking Taz1 or Tafazzin. Altered metabolism of amino acids might be involved in the pathomechanism of BTSH

Boride Coating on Titanium Alloys as Biomaterial in Wear and Fretting Applications

The issue taken into account is the lifespan and potential toxicity of arthroprostheses with a focus on metal-polyethylene coupling. The gold standard for hip prostheses is a femoral component made of Ti6Al4V alloy, a head made of Co-Cr-Mo alloy and an insert made of UHMWPE while for knee prostheses the gold standard is a tibial component made of Co-Cr-Mo alloy, a femoral component made of Ti6Al4V and an insert made of UHMWPE. Open issues are wear of UHMWPE, toxicity of Co alloys and low fretting/wear resistance of Ti alloys. The aim of this research is to focus on the most biocompatible material (Ti6Al4V alloy) in order to improve its bio-tribological characteristics. A ceramic surface conversion by thermal treatment was used to obtain a borided coating on the titanium alloy surface in order to combine high hardness, good wettability and lubricant behavior of ceramics with good mechanical properties of Ti metal alloys. The coatings were characterized by means of optical microscope observation, FESEM analysis, XRD analysis, microindentation, scratch, friction and wear tests in order to identify the thermal treatment most suitable to obtain a coating with the required properties (thickness, hardness, roughness, wear resistance, friction coefficient and scratch resistance, surface lubrication ability in contact with human fluids) without significant modification of the microstructure of the substrate

Eosinophilic Pneumonia in a Patient with Bronchial Myiasis : Case report and literature review

Pulmonary myiasis is an unusual form of myiasis in humans and has been recently identified as a cause of eosinophilic pneumonia. We report the case of a 13-year-old Omani boy who presented to the Royal Hospital, Muscat, Oman, in October 2014 with respiratory distress. Bronchial aspirates revealed features of eosinophilic pneumonia. Possible larvae identified in the cytology report, a high immunoglobulin E level and the patient history all indicated bronchial myiasis. The patient was treated with steroids and ventilation and has since been diseasefree with no long-term side-effects. To the best of the authors’ knowledge, this is the first case of bronchial myiasis in Oman