Bulk band inversion and surface Dirac cones in LaSb and LaBi : Prediction of a new topological heterostructure

We perform \textit{ab initio} investigations of the bulk and surface band structures of LaSb and LaBi and resolve the existing disagreements about the topological property of LaSb, considering LaBi as a reference. We examine the bulk band structure for band inversion, along with the stability of surface Dirac cones (if any) to time-reversal-preserving perturbations, as a strong diagnostic test for determining the topological character of LaSb, LaBi and LaSb-LaBi multilayer. A detailed \textit{ab initio} investigation of a multilayer consisting of alternating unit cells of LaSb and LaBi shows the presence of band inversion in the bulk and a massless Dirac cone on the (001) surface, which remains stable under the influence of time-reversal-preserving perturbations, thus confirming the topologically non-trivial nature of the multilayer in which the electronic properties can be tailored as per requirement. A detailed $\mathbb{Z}_2$ invariant calculation is performed to arrive at a holistic conclusion

Identification of test cases for Automated Driving Systems using Bayesian optimization

With advancements in technology, the automotive industry is experiencing a paradigm shift from assisted driving to highly automated driving. However, autonomous driving systems are highly safety critical in nature and need to be thoroughly tested for a diverse set of conditions before being commercially deployed. Due to the huge complexities involved with Advanced Driver Assistance Systems (ADAS) and Automated Driving Systems (ADS), traditional software testing methods have well-known limitations. They also fail to cover the infinite number of adverse conditions that can occur due to a slight change in the interactions between the environment and the system. Hence, it is important to identify test conditions that push the vehicle under test to breach its safe boundaries. Hazard Based Testing (HBT) methods, inspired by Systems-Theoretic Process Analysis (STPA), identify such parameterized test conditions that can lead to system failure. However, these techniques fall short of discovering the exact parameter values that lead to the failure condition. The presented paper proposes a test case identification technique using Bayesian Optimization. For a given test scenario, the proposed method learns parameter values by observing the system's output. The identified values create test cases that drive the system to violate its safe boundaries. STPA inspired outputs (parameters and pass/fail criteria) are used as inputs to the Bayesian Optimization model. The proposed method was applied to an SAE Level-4 Low Speed Automated Driving (LSAD) system which was modelled in a driving simulator

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.</p

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism

Noether current, black hole entropy and spacetime torsion

We show that the presence of spacetime torsion, unlike any other non-trivial modifications of the Einstein gravity, does not affect black hole entropy. The theory being diffeomorphism invariant leads to a Noether current and hence to a Noether charge, which can be associated to the heat content of the spacetime. Furthermore, the evolution of the spacetime inheriting torsion can be encoded in the difference between suitably defined surface and bulk degrees of freedom. For static spacetimes the surface and bulk degrees of freedom coincides, leading to holographic equipartition. In doing so one can see that the surface degrees of freedom originate from horizon area and it is clear that spacetime torsion never contributes to the surface degrees of freedom and hence neither to the black hole entropy. We further show that the gravitational Hamiltonian in presence of torsion does not inherit any torsion dependence in the boundary term and hence the first law originating from the variation of the Hamiltonian, relates entropy to area. This reconfirms our claim that torsion does not modify the black hole entropy

Transforming Curves on Surfaces

We describe an optimal algorithm to decide if one closed curve on a triangulated 2-manifold can be continuously transformed to another, i.e., if they are homotopic. Suppose C 1 and C 2 are two closed curves on a surface M of genus g. Further, suppose T is a triangulation of M of size n such that C 1 and C 2 are represented as edge-vertex sequences of lengths k 1 and k 2 in T , respectively. Then, our algorithm decides if C 1 and C 2 are homotopic in O(n+k 1 +k 2 ) time and space, provided g 6= 2 if M orientable, and g 6= 3; 4 if M is non-orientable. This as well implies an optimal algorithm to decide if a closed curve on a surface can be continuously contracted to a point. Except for three low genus cases, our algorithm completes an investigation into the computational complexity of two classical problems for surfaces posed by the mathematician Max Dehn at the beginning of this century. The novelty of our approach is in the application of methods from modern combinatorial group theory..