Security-oriented cloud computing platform for critical infrastructures

The rise of virtualisation and cloud computing is one of the most significant features of computing in the last 10 years. However, despite its popularity, there are still a number of technical barriers that prevent it from becoming the truly ubiquitous service it has the potential to be. Central to this are the issues of data security and the lack of trust that users have in relying on cloud services to provide the foundation of their IT infrastructure. This is a highly complex issue, which covers multiple inter-related factors such as platform integrity, robust service guarantees, data and network security, and many others that have yet to be overcome in a meaningful way. This paper presents a concept for an innovative integrated platform to reinforce the integrity and security of cloud services and we apply this in the context of Critical Infrastructures to identify the core requirements, components and features of this infrastructure

On the Modelling of Immiscible Viscous Fingering in Two Phase Flow in Porous Media

Viscous fingering in porous media is an instability which occurs when a low-viscosity injected fluid displaces a much more viscous resident fluid, under miscible or immiscible conditions. Immiscible viscous fingering is more complex and has been found to be difficult to simulate numerically and is the main focus of this paper. Many researchers have identified the source of the problem of simulating realistic immiscible fingering as being in the numerics of the process, and a large number of studies have appeared applying high-order numerical schemes to the problem with some limited success. We believe that this view is incorrect and that the solution to the problem of modelling immiscible viscous fingering lies in the physics and related mathematical formulation of the problem. At the heart of our approach is what we describe as the resolution of the “M-paradox”, where M is the mobility ratio, as explained below. In this paper, we present a new 4-stage approach to the modelling of realistic two-phase immiscible viscous fingering by (1) formulating the problem based on the experimentally observed fractional flows in the fingers, which we denote as f∗w, and which is the chosen simulation input; (2) from the infinite choice of relative permeability (RP) functions, k∗rw and k∗ro, which yield the same f∗w, we choose the set which maximises the total mobility function, λT (where λT=λo+λw), i.e. minimises the pressure drop across the fingering system; (3) the permeability structure of the heterogeneous domain (the porous medium) is then chosen based on a random correlated field (RCF) in this case; and finally, (4) using a sufficiently fine numerical grid, but with simple transport numerics. Using our approach, realistic immiscible fingering can be simulated using elementary numerical methods (e.g. single-point upstreaming) for the solution of the two-phase fluid transport equations. The method is illustrated by simulating the type of immiscible viscous fingering observed in many experiments in 2D slabs of rock where water displaces very viscous oil where the oil/water viscosity ratio is (μo/μw)=1600. Simulations are presented for two example cases, for different levels of water saturation in the main viscous finger (i.e. for 2 different underlying f∗w functions) produce very realistic fingering patterns which are qualitatively similar to observations in several respects, as discussed. Additional simulations of tertiary polymer flooding are also presented for which good experimental data are available for displacements in 2D rock slabs (Skauge et al., in: Presented at SPE Improved Oil Recovery Symposium, 14–18 April, Tulsa, Oklahoma, USA, SPE-154292-MS, 2012. https://doi.org/10.2118/154292-MS, EAGE 17th European Symposium on Improved Oil Recovery, St. Petersburg, Russia, 2013; Vik et al., in: Presented at SPE Europec featured at 80th EAGE Conference and Exhibition, Copenhagen, Denmark, SPE-190866-MS, 2018. https://doi.org/10.2118/190866-MS). The finger patterns for the polymer displacements and the magnitude and timing of the oil displacement response show excellent qualitative agreement with experiment, and indeed, they fully explain the observations in terms of an enhanced viscous crossflow mechanism (Sorbie and Skauge, in: Proceedings of the EAGE 20th Symposium on IOR, Pau, France, 2019). As a sensitivity, we also present some example results where the adjusted fractional flow (f∗w) can give a chosen frontal shock saturation, S∗wf, but at different frontal mobility ratios, M(S∗wf). Finally, two tests on the robustness of the method are presented on the effect of both rescaling the permeability field and on grid coarsening. It is demonstrated that our approach is very robust to both permeability field rescaling, i.e. where the (kmax/kmin) ratio in the RCF goes from 100 to 3, and also under numerical grid coarsening.publishedVersio

Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH

Background Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Methodology/Principal Findings Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)t​hiazole-4-carboxylateinhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism. Conclusions/Significance These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents

Fruit softening: evidence for rhamnogalacturonan lyase action in vivo in ripe fruit cell walls

Background and aims The softening of ripening fruit involves partial depolymerisation of cell-wall pectin by three types of reaction: enzymic hydrolysis, enzymic elimination (lyase-catalysed) and non-enzymic oxidative scission. Two known lyase activities are pectate lyase and rhamnogalacturonan lyase (RGL), potentially causing mid-chain cleavage of homogalacturonan and rhamnogalacturonan-I (RG-I) domains of pectin respectively. However, the important biological question of whether RGL exhibits action in vivo had not been tested.Methods We developed a method for specifically and sensitively detecting in-vivo RGL products, based on Driselase digestion of cell walls and detection of a characteristic unsaturated ‘fingerprint’ product (tetrasaccharide) of RGL action. Key Results In model experiments, potato RG-I that had been partially cleaved in vitro by commercial RGL was digested by Driselase, releasing an unsaturated tetrasaccharide (‘UA-Rha-GalA-Rha’), taken as diagnostic of RGL action. This highly acidic fingerprint compound was separated from monosaccharides (galacturonate, galactose, rhamnose etc.) by electrophoresis at pH 2, then separated from UA–GalA (the fingerprint of pectate lyase action) by thin-layer chromatography (TLC). The ‘UA-Rha-GalA-Rha’ was confirmed as 4-deoxy--L-threo-hex-4-enopyranuronosyl-(12)-L-rhamnosyl-(14)-D-galacturonosyl-(12)-L-rhamnose by mass spectrometry and acid hydrolysis. Driselase digestion of cell walls from diverse ripe fruits [date, sea buckthorn, cranberry, yew (arils), mango, plum, blackberry, apple, pear and strawberry] yielded the same fingerprint compound, demonstrating that RGL had been acting in vivo in these fruits prior to harvest. The ‘fingerprint’ : (galacturonate + rhamnose) ratio in digests from ripe dates was approximately 1:72 (mol/mol), indicating that ~1.4% of the backbone RhaGalA bonds in endogenous RG-I had been cleaved by in-vivo RGL action. Conclusions The results provide the first demonstration that RGL, previously known from studies of fruit gene expression, proteomic studies and in-vitro enzyme activity, exhibits enzyme action in the walls of soft fruits and may thus be proposed to contribute to fruit softening. <br/

Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST)

BACKGROUND: Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. METHODS: Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12\u2009months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. RESULTS: Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r =\u20090.61, p =\u20090.0037, Leicester Cough Questionnaire, r =\u2009-\u20090.52,p =\u20090.0015, St Georges Respiratory Questionnaire, r =\u20090.61,p &lt;\u20090.0001 and 6\u2009min walk test, r =\u2009-\u20090.46,p =\u20090.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3\u2009days (SD 5.7). A minimum clinically important difference of 4 points is proposed. CONCLUSIONS: The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials