A software approach to defeating side channels in last-level caches

We present a software approach to mitigate access-driven side-channel attacks that leverage last-level caches (LLCs) shared across cores to leak information between security domains (e.g., tenants in a cloud). Our approach dynamically manages physical memory pages shared between security domains to disable sharing of LLC lines, thus preventing "Flush-Reload" side channels via LLCs. It also manages cacheability of memory pages to thwart cross-tenant "Prime-Probe" attacks in LLCs. We have implemented our approach as a memory management subsystem called CacheBar within the Linux kernel to intervene on such side channels across container boundaries, as containers are a common method for enforcing tenant isolation in Platform-as-a-Service (PaaS) clouds. Through formal verification, principled analysis, and empirical evaluation, we show that CacheBar achieves strong security with small performance overheads for PaaS workloads

Developing the MTO Formalism

We review the simple linear muffin-tin orbital method in the atomic-spheres approximation and a tight-binding representation (TB-LMTO-ASA method), and show how it can be generalized to an accurate and robust Nth order muffin-tin orbital (NMTO) method without increasing the size of the basis set and without complicating the formalism. On the contrary, downfolding is now more efficient and the formalism is simpler and closer to that of screened multiple-scattering theory. The NMTO method allows one to solve the single-electron Schroedinger equation for a MT-potential -in which the MT-wells may overlap- using basis sets which are arbitrarily minimal. The substantial increase in accuracy over the LMTO-ASA method is achieved by substitution of the energy-dependent partial waves by so-called kinked partial waves, which have tails attached to them, and by using these kinked partial waves at N+1 arbitrary energies to construct the set of NMTOs. For N=1 and the two energies chosen infinitesimally close, the NMTOs are simply the 3rd-generation LMTOs. Increasing N, widens the energy window, inside which accurate results are obtained, and increases the range of the orbitals, but it does not increase the size of the basis set and therefore does not change the number of bands obtained. The price for reducing the size of the basis set through downfolding, is a reduction in the number of bands accounted for and -unless N is increased- a narrowing of the energy window inside which these bands are accurate. A method for obtaining orthonormal NMTO sets is given and several applications are presented.Comment: 85 pages, Latex2e, Springer style, to be published in: Lecture notes in Physics, edited by H. Dreysse, (Springer Verlag

Third-Generation TB-LMTO

We describe the screened Korringa-Kohn-Rostoker (KKR) method and the third-generation linear muffin-tin orbital (LMTO) method for solving the single-particle Schroedinger equation for a MT potential. The simple and popular formalism which previously resulted from the atomic-spheres approximation (ASA) now holds in general, that is, it includes downfolding and the combined correction. Downfolding to few-orbital, possibly short-ranged, low-energy, and possibly orthonormal Hamiltonians now works exceedingly well, as is demonstrated for a high-temperature superconductor. First-principles sp3 and sp3d5 TB Hamiltonians for the valence and lowest conduction bands of silicon are derived. Finally, we prove that the new method treats overlap of the potential wells correctly to leading order and we demonstrate how this can be exploited to get rid of the empty spheres in the diamond structure.Comment: latex2e, 32 printed pages, Postscript figs, to be published in: Tight-Binding Approach to Computational Materials Science, MRS Symposia Proceedings No. 491 (MRS, Pittsburgh, 1998

po 268 the interaction of herg1 potassium channels with integrin receptors perturbs the force transduction machinery in pancreatic cancer

Introduction Ion channels regulate cell proliferation, differentiation, and migration through cell-cell and cell–extracellular matrix interactions mediated by integrins. K + flux through the human ether-a-gogo–related gene 1 (hERG1) channel shapes action potential firing in excitable cells, e.g. cardiomyocytes. Its abundance is often aberrantly high in human tumours, including the pancreatic ductal adenocarcinoma (PDAC). We recently demonstrated that the direct interaction of β1 integrins with hERG1 channels in cancer cells stimulated distinct signalling pathways that depended on the conformational state of hERG1 and affected different aspects of tumour progression. 1 We hypothesised that hERG1 channels compromise the PDAC mechano-reciprocity, the ability to dynamically respond to externally applied forces by exerting forces, which enhances invasion and compromises treatment. Material and methods Using elastic micropillar arrays of varying stiffness, 2 we quantified the β1-integrin mediated forces exerted by PANC-1 cells. Micropillars coating with collagen and/or fibronectin derived peptides allowed us to direct cell surface receptor binding specificity (i.e. α 2 β 1 and α 5 β 1 integrins). Results and discussions Independently of the substrate coating, PANC-1 cells exerted higher forces as a function of substrate stiffness, as already demonstrated for other cell types. Remarkably, the disruption of the β1/hERG1 interaction through E4031 inhibition of hERG1 channels resulted in a significant increase in the detected cellular forces. Our results suggest that in addition to alter distinct signalling pathways 1 the direct interaction of β1 integrins and hERG1 channels perturbs the force transduction machinery. Conclusion These findings encouraged us to develop bispecific antibodies (scDb, single-chain diabody) binding to the β1/hERG1 complex that are now being validated in PDAC cell lines. In particular, we have developed a bispecific antibody (scDb-β1/hERG1), 3 which is composed by the variable domains (VH and VL chains) of monoclonal antibodies binding two different antigens, hERG1 and β1 integrin. References Becchetti, et al. Science Signaling2017;10, eaaf3236. van Hoorn, et al. Nano Lett2014;14:4257. A. Arcangeli, C. Duranti, S. Crescioli, L. Carraresi. Patent Ref: 102017000083637 (University of Florence)

Preferential closed channel blockade of HERG potassium currents by chemically synthesised BeKm‐1 scorpion toxin

The scorpion toxin peptide BeKm‐1 was synthesised by fluorenylmethoxycarbonyl solid phase chemistry and folded by air oxidation. The peptide's effects on heterologous human ether‐a‐go‐go‐related gene potassium current (I HERG) in HEK293 cells were assessed using 'whole‐cell' patch clamp. Blockade of I HERG by BeKm‐1 was concentration‐dependent, temperature‐dependent, and rapid in onset and reversibility. Blockade also exhibited inverse voltage dependence, inverse dependence on duration of depolarisation, and reverse use‐ and frequency‐dependence. Blockade by BeKm‐1 and recombinant ergtoxin, another scorpion toxin known to block HERG, differed in their recovery from HERG current inactivation elicited by strong depolarisation and in their ability to block HERG when the channels were already activated. We conclude that synthetic BeKm‐1 toxin blocks HERG preferentially through a closed (resting) state channel blockade mechanism, although some open channel blockade also occurs

Biosensors in occupational safety and health management: A narrative review

A sensor is a device used to gather information registered by some biological, physical or chemical change, and then convert the information into a measurable signal. The first biosensor prototype was conceived more than a century ago, in 1906, but a properly defined biosensor was only developed later in 1956. Some of them have reached the commercial stage and are routinely used in environmental and agricultural applications, and especially, in clinical laboratory and industrial analysis, mostly because it is an economical, simple and efficient instrument for the in situ detection of the bioavailability of a broad range of environmental pollutants. We propose a narrative review, that found 32 papers and aims to discuss the possible uses of biosensors, focusing on their use in the area of occupational safety and health (OSH)

On-site correlation in valence and core states of ferromagnetic nickel

We present a method which allows to include narrow-band correlation effects into the description of both valence and core states and we apply it to the prototypical case of nickel. The results of an ab-initio band calculation are used as input mean-field eigenstates for the calculation of self-energy corrections and spectral functions according to a three-body scattering solution of a multi-orbital Hubbard hamiltonian. The calculated quasi-particle spectra show a remarkable agreement with photoemission data in terms of band width, exchange splitting, satellite energy position of valence states, spin polarization of both the main line and the satellite of the 3p core level.Comment: 14 pages, 10 PostScript figures, RevTeX, submitted to PR

po 317 a novel bispecific antibody to harness the herg1 β1 macromolecular complex for cancer therapy

Introduction Among hindrances in cancer treatment, the lack of appropriate markers to be exploited for targeted therapy, and the need of new potential drugs are two big challenges.hERG1 potassium channels area novel class of oncological targets and one of the most intriguing aspects of their involvement in tumour establishment and progression is the interaction with adhesion molecules, such as integrins. It has been recently demonstrated that macromolecular complexes formed between hERG1 and β1 integrins selectively occurs in many types of cancer (Becchetti A et al., 2017). In this scenario, hERG1 could be exploited as a therapeutic target providing non cardiotoxic strategies aimed at blocking hERG1. Material and methods A scDb, a bifunctional single-chain diabody, directed against hERG1/β1 complex, was developed via SOE-PCR methodology. Such antibody was tested on HCT116 cells in lateral motility and western blotting experiments. Moreover immunohistochemistry (IHC) was performed on metastatic colorectal cancer (mCRC) paraffin embedded samples using the scDb, an anti-hERG1 and an anti-b1 integrin. Results and discussions Performing IHC on sequential sections of mCRC confirmed the specificity of the scDb for both hERG1 and b1 integrin. In vitro data provide evidences that the administering of the bispecific antibody has an impact on lateral motility. Moreover, signalling pathways are also affected by the antibody treatment, as AKT phosphorylation and HIF1α levels are decreased when the molecule is administered.Such findings might suggest a possible effect of the bispecific antibody on the VEGF-A signalling pathway, which are consistent with our previous hypothesis (Becchetti A et al., 2017) of a possible cross-talk leading to a deep impact on VEGF expression and, thus, on neoangiogenesis. Conclusion scDb-hERG1/β1 could be used as a potential new treatment for cancer patients and as an early molecular diagnostic marker. In fact, the selective expression of hERG1/β1 complex in cancer cells and its role in angiogenesis and cancer progression suggests that a molecule selectively targeting the complex will be an invaluable tool for cancer treatment