151 research outputs found
Requirements and Recommendations for IoT/IIoT Models to automate Security Assurance through Threat Modelling, Security Analysis and Penetration Testing
The factories of the future require efficient interconnection of their
physical machines into the cyber space to cope with the emerging need of an
increased uptime of machines, higher performance rates, an improved level of
productivity and a collective collaboration along the supply chain. With the
rapid growth of the Internet of Things (IoT), and its application in industrial
areas, the so called Industrial Internet of Things (IIoT)/Industry 4.0 emerged.
However, further to the rapid growth of IoT/IIoT systems, cyber attacks are an
emerging threat and simple manual security testing can often not cope with the
scale of large IoT/IIoT networks. In this paper, we suggest to extract metadata
from commonly used diagrams and models in a typical software development
process, to automate the process of threat modelling, security analysis and
penetration testing, without detailed prior security knowledge. In that
context, we present requirements and recommendations for metadata in IoT/IIoT
models that are needed as necessary input parameters of security assurance
tools.Comment: 8 pages, Proceedings of the 14th International Conference on
Availability, Reliability and Security (ARES 2019) (ARES '19), August 26-29,
2019, Canterbury, United Kingdo
Discovery of a Damped Lyα Galaxy at z ∼ 3 toward the Quasar SDSS J011852+040644
We report the detection of the host galaxy of a damped Lyα system (DLA) with log N(H I) [cm−2 ] = 21.0 ± 0.10 at z ≈ 3.0091 toward the background quasar SDSS J011852+040644 using the Palomar Cosmic Web Imager at the Hale (P200) telescope. We detect Lyα emission in the dark core of the DLA trough at a 3.3σ confidence level, with Lyα luminosity of LLyα = (3.8 ± 0.8) × 1042 erg s−1 , corresponding to a star formation rate of 2 Me yr−1 (considering a lower limit on Lyα escape fraction ~a f esc Ly 2%) as typical for Lyman break galaxies at these redshifts. The Lyα emission is blueshifted with respect to the systemic redshift derived from metal absorption lines by 281 ± 43 km s−1 . The associated galaxy is at very small impact parameter of 12 kpc from the background quasar, which is in line with the observed anticorrelation between column density and impact parameter in spectroscopic searches tracing the large-scale environments of DLA host galaxies
Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy
Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore the structural determinants of ALDH1A isoform selectivity in a series of small-molecule inhibitors in support of research into the role of ALDH1A in cancer stem cells. An SAR campaign guided by a cocrystal structure of the HTS hit CM39 (7) with ALDH1A1 afforded first-in-class inhibitors of the ALDH1A subfamily with excellent selectivity over the homologous ALDH2 isoform. We also discovered the first reported modestly selective single isoform 1A2 and 1A3 inhibitors. Two compounds, 13g and 13h, depleted the CD133+ putative cancer stem cell pool, synergized with cisplatin, and achieved efficacious concentrations in vivo following IP administration. Compound 13h additionally synergized with cisplatin in a patient-derived ovarian cancer spheroid model
Dynamic plasmonic beam shaping by vector beams with arbitrary locally linear polarization states
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Application of an acoustofluidic perfusion bioreactor for cartilage tissue engineering
Cartilage grafts generated using conventional static tissue engineering strategies are characterised by low cell viability, suboptimal hyaline cartilage formation and, critically, inferior mechanical competency, which limit their application for resurfacing articular cartilage defects. To address the limitations of conventional static cartilage bioengineering strategies and generate robust, scaffold-free neocartilage grafts of human articular chondrocytes, the present study utilised custom-built microfluidic perfusion bioreactors with integrated ultrasound standing wave traps. The system employed sweeping acoustic drive frequencies over the range of 890 to 910 kHz and continuous perfusion of the chondrogenic culture medium at a low-shear flow rate to promote the generation of three-dimensional agglomerates of human articular chondrocytes, and enhance cartilage formation by cells of the agglomerates via improved mechanical stimulation and mass transfer rates. Histological examination and assessment of micromechanical properties using indentation-type atomic force microscopy confirmed that the neocartilage grafts were analogous to native hyaline cartilage. Furthermore, in the ex vivo organ culture partial thickness cartilage defect model, implantation of the neocartilage grafts into defects for 16 weeks resulted in the formation of hyaline cartilage-like repair tissue that adhered to the host cartilage and contributed to significant improvements to the tissue architecture within the defects, compared to the empty defects. The study has demonstrated the first successful application of the acoustofluidic perfusion bioreactors to bioengineer scaffold-free neocartilage grafts of human articular chondrocytes that have the potential for subsequent use in second generation autologous chondrocyte implantation procedures for the repair of partial thickness cartilage defects
β-Elemene Piperazine Derivatives Induce Apoptosis in Human Leukemia Cells through Downregulation of c-FLIP and Generation of ROS
β-Elemene is an active component of the herb medicine Curcuma Wenyujin with reported antitumor activity. To improve its antitumor ability, five novel piperazine derivatives of β-elemene, 13-(3-methyl-1-piperazinyl)-β-elemene (DX1), 13-(cis-3,5-dimethyl-1-piperazinyl)-β-elemene (DX2), 13-(4-ethyl-1-piperazinyl)-β-elemene (DX3), 13-(4-isopropyl-1-piperazinyl)-β-elemene (DX4) and 13-piperazinyl-β-elemene (DX5), were synthesized. The antiproliferative and apoptotic effects of these derivatives were determined in human leukemia HL-60, NB4, K562 and HP100-1 cells. DX1, DX2 and DX5, which contain a secondary amino moiety, were more active in inhibiting cell growth and in inducing apoptosis than DX3 and DX4. The apoptosis induction ability of DX1 was associated with the generation of hydrogen peroxide (H2O2), a decrease of mitochondrial membrane potential (MMP), and the activation of caspase-8. Pretreatment with the antioxidants N-acetylcysteine and catalase completely blocked DX1-induced H2O2 production, but only partially its activation of caspase-8 and induction of apoptosis. HL-60 cells were more sensitive than its H2O2-resistant subclone HP100-1 cells to DX1-induced apoptosis. The activation of caspase-8 by these compounds was correlated with the decrease in the levels of cellular FLICE-inhibitory protein (c-FLIP). The proteasome inhibitor MG-132 augmented the decrease in c-FLIP levels and apoptosis induced by these derivatives. FADD- and caspase-8-deficient Jurkat subclones have a decreased response to DX1-induced apoptosis. Our data indicate that these novel β-elemene piperazine derivatives induce apoptosis through the decrease in c-FLIP levels and the production of H2O2 which leads to activation of both death receptor- and mitochondrial-mediated apoptotic pathways
Distinct white matter microstructural abnormalities and extracellular water increases relate to cognitive impairment in Alzheimer’s disease with and without cerebrovascular disease
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