A Framework to Simulate and Improve Terahertz Quantum Well Photodetectors

A wide range of applications have been recognized for terahertz radiations. In fact, medical imaging, homeland security screening, very high-speed wireless telecommunications systems and even drug and gas detection are boosting the development of terahertz emitters and receivers. The work of this thesis is among the efforts in that regard. Actual terahertz detectors are suffering many drawbacks, they are bulky, very slow, not very sensitive or operates at non-practical temperatures. Combined with the complexity to realize terahertz emitters, it explains the difficulties of terahertz radiations to ensure market penetration with practicable civil applications. In that regard, we aim to better understand and improve a specific terahertz photodetector: the Terahertz Quantum Well Photodetector. Those devices working principle relies on a photocurrent created by the excitation of electrons from ground states of quantum wells to the continuum under terahertz impinging light. The intensity of the photocurrent is depending on the intensity of the radiation received by the device. The device active region is made of a multiple quantum wells GaAs/AlGaAs system. By changing the design of the device, that is the thicknesses of each layer, the aluminum fraction of the doping concentration, we can modify its performances. Documented and commented Matlab functions and routines have been implemented in order to simulate a given structure and scripts have been written to find the optimum parameters for a target absorption frequency. Our model has been verified by comparison with experimental data reported in the literature. Based on our model, we systematically study the impact of the active region and contact parameters on the device performances. In addition, innovative designs are proposed in order to reduce the undesirable dark current and thus increase the detectivity. They benefits from many-body effects, effects that are usually a constraint on the design. To our knowledge this is the first time those effects are used to realize innovative designs and increase the performances of quantum well infrared photodetectors. Finally we expose other designs that have been tested in the infrared domain with QWIP and adapt them to the terahertz range. In particular, we propose a quantum cascade photodetector, a double barrier bound-to-miniband and a phonon-assisted band to miniband structures

Augment to Interpret: Unsupervised and Inherently Interpretable Graph Embeddings

Unsupervised learning allows us to leverage unlabelled data, which has become abundantly available, and to create embeddings that are usable on a variety of downstream tasks. However, the typical lack of interpretability of unsupervised representation learning has become a limiting factor with regard to recent transparent-AI regulations. In this paper, we study graph representation learning and we show that data augmentation that preserves semantics can be learned and used to produce interpretations. Our framework, which we named INGENIOUS, creates inherently interpretable embeddings and eliminates the need for costly additional post-hoc analysis. We also introduce additional metrics addressing the lack of formalism and metrics in the understudied area of unsupervised-representation learning interpretability. Our results are supported by an experimental study applied to both graph-level and node-level tasks and show that interpretable embeddings provide state-of-the-art performance on subsequent downstream tasks

Transcriptomic analysis of three Veillonella spp. present in carious dentine and in the saliva of caries-free individuals.

Veillonella spp. are predominant bacteria found in all oral biofilms. In this study, a metatranscriptomic approach was used to investigate the gene expression levels of three oral Veillonella spp. (V. parvula, V. dispar and V. atypica) in whole stimulated saliva from caries-free volunteers and in carious lesions (n=11 for each group). In the lesions the greatest proportion of reads were assigned to V. parvula and genes with the highest level of expression in carious samples were those coding for membrane transport systems. All three Veillonella spp. increased expression of genes involved in the catabolism of lactate and succinate, notably the alpha- and beta-subunits of L(+)-tartrate dehydratase (EC 4.2.1.32). There was also significantly increased expression of histidine biosynthesis pathway in V. parvula, suggesting higher intra-cellular levels of histidine that could provide intra-cellular buffering capacity and, therefore, assist survival in the acidic environment. Various other systems such as potassium uptake systems were also up regulated that may aid in the survival and proliferation of V. parvula in carious lesions

CAD-Based Design Optimization of Four-Bar Mechanisms: An Emergency Ventilator Case Study

The design optimization of mechanisms is promising as it results in more energy-efficient machines without compromising performance. However, machine builders do not apply state-of-the-art methods, as these algorithms require case-specific theoretical analysis. Moreover, the design synthesis approaches in the literature predominantly utilize heuristic optimizers, leading to suboptimal local minima. This paper introduces a widely applicable workflow, guaranteeing the global optimum. The constraints describing the feasible region of the possible designs are essential to find the global optimum. Therefore, kinematic analysis of the point-to-point planar four-bar mechanism is discussed. Within the feasible design space, objective value samples were generated through the CAD multi-body software. These motion simulations determine the required torque to fulfill the movement for a combination of design parameters. This replaces the cumbersome analytic derivation of the torque. This paper introduces sparse interpolation techniques to avoid brute force sampling of the design space. The advantage of this approach is that it is easily scalable to more design parameters, as the interpolation method minimizes the number of necessary samples. This paper explains the mathematical background of our developed interpolation approach. However, a step-by-step procedure is introduced to allow the employment of the interpolation technique by machine designers without the necessity to understand the underlying mathematics. Finally, the mathematical expression, obtained from the interpolation, enables applying global optimizers. In a case study of an emergency ventilator mechanism with three design parameters, 1870 CAD motion simulations allowed reducing the RMS torque of the mechanism by 67

CAD-Based Design Optimization of Four-Bar Mechanisms: An Emergency Ventilator Case Study

The design optimization of mechanisms is promising as it results in more energy-efficient machines without compromising performance. However, machine builders do not apply state-of-the-art methods, as these algorithms require case-specific theoretical analysis. Moreover, the design synthesis approaches in the literature predominantly utilize heuristic optimizers, leading to suboptimal local minima. This paper introduces a widely applicable workflow, guaranteeing the global optimum. The constraints describing the feasible region of the possible designs are essential to find the global optimum. Therefore, kinematic analysis of the point-to-point planar four-bar mechanism is discussed. Within the feasible design space, objective value samples were generated through the CAD multi-body software. These motion simulations determine the required torque to fulfill the movement for a combination of design parameters. This replaces the cumbersome analytic derivation of the torque. This paper introduces sparse interpolation techniques to avoid brute force sampling of the design space. The advantage of this approach is that it is easily scalable to more design parameters, as the interpolation method minimizes the number of necessary samples. This paper explains the mathematical background of our developed interpolation approach. However, a step-by-step procedure is introduced to allow the employment of the interpolation technique by machine designers without the necessity to understand the underlying mathematics. Finally, the mathematical expression, obtained from the interpolation, enables applying global optimizers. In a case study of an emergency ventilator mechanism with three design parameters, 1870 CAD motion simulations allowed reducing the RMS torque of the mechanism by 67

Boosting mitochondria activity by silencing MCJ overcomes cholestasis-induced liver injury

Background & Aims: Mitochondria are the major organelles for the formation of reactive oxygen species (ROS) in the cell, and mitochondrial dysfunction has been described as a key factor in the pathogenesis of cholestatic liver disease. The methylation-controlled J-protein (MCJ) is a mitochondrial protein that interacts with and represses the function of complex I of the electron transport chain. The relevance of MCJ in the pathology of cholestasis has not yet been explored. Methods: We studied the relationship between MCJ and cholestasis-induced liver injury in liver biopsies from patients with chronic cholestatic liver diseases, and in livers and primary hepatocytes obtained from WT and MCJ-KO mice. Bile duct ligation (BDL) was used as an animal model of cholestasis, and primary hepatocytes were treated with toxic doses of bile acids. We evaluated the effect of MCJ silencing for the treatment of cholestasis-induced liver injury. Results: Elevated levels of MCJ were detected in the liver tissue of patients with chronic cholestatic liver disease when compared with normal liver tissue. Likewise, in mouse models, the hepatic levels of MCJ were increased. After BDL, MCJ-KO animals showed significantly decreased inflammation and apoptosis. In an in vitro model of bile-acid induced toxicity, we observed that the loss of MCJ protected mouse primary hepatocytes from bile acid-induced mitochondrial ROS over-production and ATP depletion, enabling higher cell viability. Finally, the in vivo inhibition of the MCJ expression, following BDL, showed reduced liver injury and a mitigation of the main cholestatic characteristics. Conclusions: We demonstrated that MCJ is involved in the progression of cholestatic liver injury, and our results identified MCJ as a potential therapeutic target to mitigate the liver injury caused by cholestasis. Lay summary: In this study, we examine the effect of mitochondrial respiratory chain inhibition by MCJ on bile acid-induced liver toxicity. The loss of MCJ protects hepatocytes against apoptosis, mitochondrial ROS overproduction, and ATP depletion as a result of bile acid toxicity. Our results identify MCJ as a potential therapeutic target to mitigate liver injury in cholestatic liver diseases.Acknowledgements: We thank MINECO for the Severo Ochoa Excellence Accreditation of CIC bioGUNE [SEV-2016-0644]

Altering an Artificial Gagpolnef Polyprotein and Mode of ENV Co-Administration Affects the Immunogenicity of a Clade C HIV DNA Vaccine

HIV-1 candidate vaccines expressing an artificial polyprotein comprising Gag, Pol and Nef (GPN) and a secreted envelope protein (Env) were shown in recent Phase I/II clinical trials to induce high levels of polyfunctional T cell responses; however, Env-specific responses clearly exceeded those against Gag. Here, we assess the impact of the GPN immunogen design and variations in the formulation and vaccination regimen of a combined GPN/Env DNA vaccine on the T cell responses against the various HIV proteins. Subtle modifications were introduced into the GPN gene to increase Gag expression, modify the expression ratio of Gag to PolNef and support budding of virus-like particles. I.m. administration of the various DNA constructs into BALB/c mice resulted in an up to 10-fold increase in Gag- and Pol-specific IFNγ+ CD8+ T cells compared to GPN. Co-administering Env with Gag or GPN derivatives largely abrogated Gag-specific responses. Alterations in the molar ratio of the DNA vaccines and spatially or temporally separated administration induced more balanced T cell responses. Whereas forced co-expression of Gag and Env from one plasmid induced predominantly Env-specific T cells responses, deletion of the only H-2d T cell epitope in Env allowed increased levels of Gag-specific T cells, suggesting competition at an epitope level. Our data demonstrate that the biochemical properties of an artificial polyprotein clearly influence the levels of antigen-specific T cells, and variations in formulation and schedule can overcome competition for the induction of these responses. These results are guiding the design of ongoing pre-clinical and clinical trials

Key Labeling Technologies to Tackle Sizeable Problems in RNA Structural Biology

The ability to adopt complex three-dimensional (3D) structures that can rapidly interconvert between multiple functional states (folding and dynamics) is vital for the proper functioning of RNAs. Consequently, RNA structure and dynamics necessarily determine their biological function. In the post-genomic era, it is clear that RNAs comprise a larger proportion (>50%) of the transcribed genome compared to proteins (≤2%). Yet the determination of the 3D structures of RNAs lags considerably behind those of proteins and to date there are even fewer investigations of dynamics in RNAs compared to proteins. Site specific incorporation of various structural and dynamic probes into nucleic acids would likely transform RNA structural biology. Therefore, various methods for introducing probes for structural, functional, and biotechnological applications are critically assessed here. These probes include stable isotopes such as 2H, 13C, 15N, and 19F. Incorporation of these probes using improved RNA ligation strategies promises to change the landscape of structural biology of supramacromolecules probed by biophysical tools such as nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography and Raman spectroscopy. Finally, some of the structural and dynamic problems that can be addressed using these technological advances are outlined