The N-terminal shuttle domain of Erv1 determines the affinity for Mia40 and mediates electron transfer to the catalytic Erv1 core in yeast mitochondria

Erv1 and Mia40 constitute the two important components of the disulfide relay system that mediates oxidative protein folding in the mitochondrial intermembrane space. Mia40 is the import receptor that recognizes the substrates introducing disulfide bonds while it is reduced. A key function of Erv1 is to recycle Mia40 to its active oxidative state. Our aims here were to dissect the domain of Erv1 that mediates the protein–protein interaction with Mia40 and to investigate the interactions between the shuttle domain of Erv1 and its catalytic core and their relevance for the interaction with Mia40. We purified these domains separately as well as cysteine mutants in the shuttle and the active core domains. The noncovalent interaction of Mia40 with Erv1 was measured by isothermal titration calorimetry, whereas their covalent mixed disulfide intermediate was analyzed in reconstitution experiments in vitro and in organello. We established that the N-terminal shuttle domain of Erv1 is necessary and sufficient for interaction to occur. Furthermore, we provide direct evidence for the intramolecular electron transfer from the shuttle cysteine pair of Erv1 to the core domain. Finally, we reconstituted the system by adding in trans the N- and C- terminal domains of Erv1 together with its substrate Mia40

Relaxed micromorphic model of transient wave propagation in anisotropic band-gap metastructures

In this paper, we show that the transient waveforms arising from several localised pulses in a micro-structured material can be reproduced by a corresponding generalised continuum of the relaxed micromorphic type. Specifically, we compare the dynamic response of a bounded micro-structured material to that of bounded continua with special kinematic properties: (i) the relaxed micromorphic continuum and (ii) an equivalent Cauchy linear elastic continuum. We show that, while the Cauchy theory is able to describe the overall behaviour of the metastructure only at low frequencies, the relaxed micromorphic model goes far beyond by giving a correct description of the pulse propagation in the frequency band-gap and at frequencies intersecting the optical branches. In addition, we observe a computational time reduction associated with the use of the relaxed micromorphic continuum, compared to the sensible computational time needed to perform a transient computation in a micro-structured domain

Relaxed micromorphic broadband scattering for finite-size meta-structures -- a detailed development

The conception of new metamaterials showing unorthodox behaviors with respect to elastic wavepropagation has become possible in recent years thanks to powerful dynamical homogenization techniques. Such methods effectively allow to describe the behavior of an infinite medium generated by periodically architectured base materials. Nevertheless, when it comes to the study of the scattering properties of finite-sized structures, dealing with the correct boundary conditions at the macroscopicscale becomes challenging. In this paper, we show how finite-domain boundary value problems canbe set-up in the framework of enriched continuum mechanics (relaxed micromorphic model) by imposing continuity of macroscopic displacement and of generalized traction when non-local effects areneglected.The case of a metamaterial slab of finite width is presented, its scattering properties are studied viaa semi-analytical solution of the relaxed micromorphic model and compared to numerical simulationsencoding all details of the selected microstructure. The reflection coefficient obtained via the twomethods is presented as a function of the frequency and of the direction of propagation of the incidentwave. We find excellent agreement for a large range of frequencies going from the long-wave limitto frequencies beyond the first band-gap and for angles of incidence ranging from normal to nearparallel incidence. The case of a semi-infinite metamaterial is also presented and is seen to be areliable measure of the average behavior of the finite metastructure. A tremendous gain in termsof computational time is obtained when using the relaxed micromorphic model for the study of theconsidered metastructure

RobustSPAM for Inference from Noisy Longitudinal Data and Preservation of Privacy

The availability of complex temporal datasets in social, health and consumer contexts has driven the development of pattern mining techniques that enable the use of classical machine learning tools for model building. In this work we introduce a robust temporal pattern mining framework for finding predictive patterns in complex timestamped multivariate and noisy data. We design an algorithm RobustSPAM that enables mining of temporal patterns from data with noisy timestamps. We apply our algorithm to social care data from a local government body and investigate how the efficiency and accuracy of the method depends on the level of noise. We further explore the trade-off between the loss of predictivity due to perturbation of timestamps and the risk of person re-identification

New developments in InAs/InGaAs quantum dot-in-a-well infrared photodetectors

This thesis presents experimental studies of InAs/InGaAs/GaAs quantum dot-in-awell infrared photodetectors (DWELL QDIPs) grown by molecular beam epitaxy (MBE). Detailed studies were carried out to investigate the effects of design parameters on the performance of DWELL photodetectors, along with fundamental studies to determine the intraband optical and electronic properties of such structures. Using the results of these studies, an optimised structure was designed. In addition, the observation of a strong bias dependent spectral photoresponse demonstrated the capability of post growth spectral tunability within the long wavelength IR (LWIR) atmospheric window. Various approaches were investigated for enhancing the performance of quantum dot (QD) based devices. The main shortcoming of QDIPs versus quantum well infrared photodetectors (QWIPs) has been addressed i.e. the low dot density, which prohibits the high doping of these structures. The use of an antimonide surfactant to enhance the dot density in DWELL QDIPs is presented here for the first time. Also a method for decreasing the dark current in QDIPs was investigated, via the use of wide band gap AIGaAs barriers. Another technique using GaP strain balancing layers to reduce the strain in multilayer structures and allow the growth of >20 layer QD devices was illustrated. The effects of intermixing via thermal annealing are also reported in for DWELL QDIPs. As part of this study, the possibility of using such a technique to shift the spectral photoresponse across the 8-12J..lm LWIR window is demonstrated, and it is shown that the performance still remains in a competitive range within the LWIR range. Non-linear two photon absorption in QDIPs was demonstrated and studied. As a result of this study, the capability of QDIPs to operate as quadratic detectors in the far-infrared was established, which could prove very significant, since detector availability is reduced in that range. Finally, a novel approach to photovoltaic QDIPs was investigated experimentally, using a purpose built design in order to provide an internal electric field, which preferentially drives carriers in one direction

Differential proteomic analysis of the reactivated p53 via Nutlin-3a, in 3 different types of human lymphomas

Purpose: The identification and quantification of protein expression levels of nutlin-3A-induced p53 stabilization and activation in human lymphoma. Methods: The Isotope Coded Protein Label (ICPL) technique was followed by nano-Liquid Chromatography coupled on-line with Mass Spectrometry (nLC-MS/MS). Results: Reliable identification & differential quantitative determination of human lymphoma proteome profile, revealing alterations in the HSPs relative expression levels