Putting Security on the Table: The Digitalisation of Security Tabletop Games and its Challenging Aftertaste

IT-Security Tabletop Games for developers have been available in analog format; with the COVID-19 pandemic, interest in collaborative remote security games has increased. In this paper, we propose a methodology to evaluate the impact of a (remote) security game-based intervention on developers. The study design consists of the respective intervention, three questionnaires, and a small open interview guide for a focus group. A validated self-efficacy scale is used as a proxy for measuring effects on participants' ability to develop secure software. We tested this design with 9 participants (expert and novice developers and security experts) as part of a small feasibility study to understand the challenges and limitations of remote tabletop games. We describe how we selected and digitalised three security tabletop games, and report the qualitative findings from our evaluation. Setting up and running the virtual tabletop games turned out to be more challenging and complex for both moderator and participants than we expected. Completing the games required patience and persistence, and social interaction was limited. Our findings can be helpful in building and evaluating a better, more comprehensive, technically sound and issue-specific game-based training measure for developers. The methodology can be used by researchers to evaluate existing and new game designs

Robust adaptive algorithms for underwater acoustic channel estimation and their performance analysis

We introduce a novel family of adaptive robust channel estimators for highly challenging underwater acoustic (UWA) channels. Since the underwater environment is highly non-stationary and subjected to impulsive noise, we use adaptive filtering techniques based on minimization of a logarithmic cost function, which results in a better trade-off between the convergence rate and the steady state performance of the algorithm. To improve the convergence performance of the conventional first and second order linear estimation methods while mitigating the stability issues related to impulsive noise, we intrinsically combine different norms of the error in the cost function using a logarithmic term. Hence, we achieve a comparable convergence rate to the faster algorithms, while significantly enhancing the stability against impulsive noise in such an adverse communication medium. Furthermore, we provide a thorough analysis for the tracking and steady-state performances of our proposed methods in the presence of impulsive noise. In our analysis, we not only consider the impulsive noise, but also take into account the frequency and phase offsets commonly experienced in real life experiments. We demonstrate the performance of our algorithms through highly realistic experiments performed on accurately simulated underwater acoustic channels. © 2017 Elsevier Inc

Genome-Wide Expression Analysis of a Spinal Muscular Atrophy Model: Towards Discovery of New Drug Targets

Spinal Muscular Atrophy is a recessive genetic disease and affects lower motor neurones and muscle tissue. A single gene is disrupted in SMA: SMN1 activity is abolished but a second copy of the gene (SMN2) provides limited activity. While the SMN protein has been shown to function in the assembly of RNA-protein complexes, it is unclear how the overall reduction in SMN activity specifically results in the neuromuscular phenotypes. Similar to humans, reduced smn activity in the fly causes earliest phenotypes in neuromuscular tissues. To uncover the effects of reduced SMN activity, we have studied gene expression in control and diseased fly tissues using whole genome micro-arrays. A number of gene expression changes are recovered and independently validated. Identified genes show trends in their predicted function: several are consistent with the function of SMN, in addition some uncover novel pathways. This and subsequent genetic analysis in the fly indicates some of the identified genes could be taken for further studies as potential drug targets for SMA and other neuromuscular disorders

Computational investigation of diesel nozzle internal flow during the complete injection event

[EN] Currently, diesel engines are calibrated using more and more complex multiple injection strategies. Under these conditions, the characteristics of the flow exiting the fuel injector are strongly affected by the transient interaction between the needle, the sac volume and the orifices, which are not yet clear. In the current paper, a methodology combining a 1D injector model and 3D-CFD simulations is proposed. First, the characteristics of the nozzle flow have been experimentally assessed in transient conditions by means of injection rate and momentum flux measurements. Later, the 3D-CFD modeling approach has been validated at steady-state fixed lift conditions. Finally, a previously developed 1D injector model has been used to extract the needle lift profiles and transient pressure boundary conditions used for the full-transient 3D-CFD simulations, using adaptive mesh refinement (AMR) strategies to be able to simulate the complete injection rate starting from 1 mu m lift.This work was partly sponsored by "Ministerio de Economia y Competitividad'', of the Spanish Government, in the frame of the Project "Estudio de la interaccion chorro-pared en condiciones realistas de motor'', Reference TRA2015-67679-c2-1-R. The authors would like also to thank the computer resources, technical expertise and assistance provided by Universidad de Valencia in the use of the supercomputer "Tirant''. Mr. Jaramillo's Thesis is funded by "Conselleria d'Educacio, Cultura i Esports'' of Generalitat Valenciana in the frame of the program "Programa VALI + D para investigadores en formacion, Reference ACIF/2015/040.Salvador, FJ.; De La Morena, J.; Bracho Leon, G.; Jaramillo-Císcar, D. (2018). Computational investigation of diesel nozzle internal flow during the complete injection event. Journal of the Brazilian Society of Mechanical Sciences and Engineering. 40(3):153-167. https://doi.org/10.1007/s40430-018-1074-zS153167403Hall CAS, Lambert JG, Balogh SB (2014) EROI of different fuels and the implications for society. Energy Policy 64:141–152. https://doi.org/10.1016/j.enpol.2013.05.049Lujan JM, Tormos B, Salvador FJ, Gargar K (2009) Comparative analysis of a DI diesel engine fuelled with biodiesel blends during the European MVEG-A cycle: preliminary study (I). Biomass Bioenergy 33:941–947. https://doi.org/10.1016/j.biombioe.2009.02.004Pickett LM, Siebers DL (2004) Soot in diesel fuel jets: effects of ambient temperature, ambient density, and injection pressure. Combust Flame 138:114–135. https://doi.org/10.1016/j.combustflame.2004.04.006Dec JE (1997) A Conceptual Model of DI Diesel Combustion Based on Laser-Sheet Imaging. SAE Tech. Pap. 970873Wang X, Huang Z, Zhang W et al (2011) Effects of ultra-high injection pressure and micro-hole nozzle on flame structure and soot formation of impinging diesel spray. Appl Energy 88:1620–1628. https://doi.org/10.1016/j.apenergy.2010.11.035Sayin C, Gumus M, Canakci M (2013) Influence of injector hole number on the performance and emissions of a di diesel engine fueled with biodiesel-diesel fuel blends. Appl Therm Eng 61:121–128. https://doi.org/10.1016/j.applthermaleng.2013.07.038Mohan B, Yang W, Chou SK (2013) Fuel injection strategies for performance improvement and emissions reduction in compression ignition engines—A review. Renew Sustain Energy Rev 28:664–676. https://doi.org/10.1016/j.rser.2013.08.051Payri R, Salvador FJ, Gimeno J, De la Morena J (2011) Influence of injector technology on injection and combustion development, Part 1: hydraulic characterization. Appl Energy 88:1068–1074. https://doi.org/10.1016/j.apenergy.2010.10.012Park SW, Kim JW, Lee CS (2006) Effect of injector type on fuel-air mixture formation of high-speed diesel sprays. Proc Inst Mech Eng D 220:647–659. https://doi.org/10.1243/09544070D20304Moon S, Komada K, Sato K et al (2015) Ultrafast X-ray study of multi-hole GDI injector sprays: effects of nozzle hole length and number on initial spray formation. Exp Therm Fluid Sci 68:68–81. https://doi.org/10.1016/j.expthermflusci.2015.03.027Powell CF, Kastengren AL, Liu Z, Fezzaa K (2010) The effects of diesel injector needle motion on spray structure. J Eng Gas Turbines Power 133:12802. https://doi.org/10.1115/1.4001073Huang W, Moon S, Ohsawa K (2016) Near-nozzle dynamics of diesel spray under varied needle lifts and its prediction using analytical model. Fuel 180:292–300. https://doi.org/10.1016/j.fuel.2016.04.042Sun Z-Y, Li G-X, Chen C et al (2015) Numerical investigation on effects of nozzle’s geometric parameters on the flow and the cavitation characteristics within injector’s nozzle for a high-pressure common-rail DI diesel engine. Energy Convers Manag 89:843–861. https://doi.org/10.1016/j.enconman.2014.10.047Devassy BM, Habchi C, Daniel E (2015) Atomization modelling of liquid jets using a two-surface density approach. At Sprays 25:47–80Moon S, Gao Y, Park S et al (2015) Effect of the number and position of nozzle holes on in- and near-nozzle dynamic characteristics of diesel injection. Fuel 150:112–122. https://doi.org/10.1016/j.fuel.2015.01.097Payri R, Salvador FJ, Carreres M, De la Morena J (2016) Fuel temperature influence on the performance of a last generation common-rail diesel ballistic injector. Part II: 1D model development, validation and analysis. Energy Convers Manag 114:376–391. https://doi.org/10.1016/j.enconman.2016.02.043Plamondon E, Seers P (2014) Development of a simplified dynamic model for a piezoelectric injector using multiple injection strategies with biodiesel/diesel-fuel blends. Appl Energy 131:411–424. https://doi.org/10.1016/j.apenergy.2014.06.039Postrioti L, Malaguti S, Bosi M et al (2014) Experimental and numerical characterization of a direct solenoid actuation injector for diesel engine applications. Fuel 118:316–328. https://doi.org/10.1016/j.fuel.2013.11.001Desantes JM, Salvador FJ, Lopez JJ, De la Morena J (2011) Study of mass and momentum transfer in diesel sprays based on X-ray mass distribution measurements and on a theoretical derivation. Exp Fluids 50:233–246. https://doi.org/10.1007/s00348-010-0919-8De la Morena J, Neroorkar K, Plazas AH et al (2013) Numerical analysis of the influence of diesel nozzle design on internal flow characteristics for 2-valve diesel engine application. At Sprays 23:97–118. https://doi.org/10.1615/AtomizSpr.2013006361Duke DJ, Schmidt DP, Neroorkar K et al (2013) High-resolution large eddy simulations of cavitating gasoline-ethanol blends. Int J Engine Res 14:578–589. https://doi.org/10.1177/1468087413501824Mitroglou N, McLorn M, Gavaises M et al (2014) Instantaneous and ensemble average cavitation structures in diesel micro-channel flow orifices. Fuel 116:736–742. https://doi.org/10.1016/j.fuel.2013.08.060Wang X, Li K, Su W (2012) Experimental and numerical investigations on internal flow characteristics of diesel nozzle under real fuel injection conditions. Exp Therm Fluid Sci 42:204–211. https://doi.org/10.1016/j.expthermflusci.2012.04.022Sou A, Pratama RH (2016) Effects of asymmetric inflow on cavitation in fuel injector and discharged liquid jet. At Sprays 26:939–959. https://doi.org/10.1615/AtomizSpr.2015013501Xue Q, Battistoni M, Powell CF et al (2015) An Eulerian CFD model and X-ray radiography for coupled nozzle flow and spray in internal combustion engines. Int J Multiph Flow 70:77–88. https://doi.org/10.1016/j.ijmultiphaseflow.2014.11.012Castilla R, Gamez-Montero PJ, Ertrk N et al (2010) Numerical simulation of turbulent flow in the suction chamber of a gearpump using deforming mesh and mesh replacement. Int J Mech Sci 52:1334–1342. https://doi.org/10.1016/j.ijmecsci.2010.06.009Parlak Z, Engin T (2012) Time-dependent CFD and quasi-static analysis of magnetorheological fluid dampers with experimental validation. Int J Mech Sci 64:22–31. https://doi.org/10.1016/j.ijmecsci.2012.08.006Chiatti G, Chiavola O, Palmieri F (2009) Spray modeling for diesel engine performance analysis. SAE Tech Pap 2009-01-0835. https://doi.org/10.4271/2009-01-0835Marcer R, Audiffren C, Viel A, et al (2010) Coupling 1D system AMESim and 3D CFD EOLE models for diesel injection simulation Renault. In: ILASS—Eur. 2010, 23rd Annu. Conf. Liq. At. Spray Syst., pp 1–10Desantes JM, Salvador FJ, Carreres M, Martínez-López J (2014) Large-eddy simulation analysis of the influence of the needle lift on the cavitation in diesel injector nozzles. Proc Inst Mech Eng D 229:407–423. https://doi.org/10.1177/0954407014542627Battistoni M, Xue Q, Som S (2016) Large-eddy simulation (LES) of spray transients: start and end of injection phenomena. Oil Gas Sci Technol 71:24. https://doi.org/10.2516/ogst/2015024CONVERGE is a trade mark of convergent science. https://convergecfd.comMacian V, Bermúdez V, Payri R, Gimeno J (2003) New technique for determination of internal geometry of a diesel nozzle with the use of silicone methodology. Exp Tech 27:39–43. https://doi.org/10.1111/j.1747-1567.2003.tb00107.xDabiri S, Sirignano WA, Joseph DD (2007) Cavitation in an orifice flow. Phys Fluids 19:72112. https://doi.org/10.1063/1.2750655Mohan B, Yang W, Chou SK (2014) Cavitation in injector nozzle holes—a parametric study. Eng Appl Comput Fluid Mech 8:70–81Salvador FJ, Hoyas S, Novella R, Martinez-Lopez J (2011) Numerical simulation and extended validation of two-phase compressible flow in diesel injector nozzles. Proc Inst Mech Eng D 225:545–563. https://doi.org/10.1177/09544070JAUTO1569Som S, Longman DE, Ramirez AI, Aggarwal S (2012) Influence of nozzle orifice geometry and fuel properties on flow and cavitation characteristics of a diesel injector. In: Fuel Inject. Automot. Eng., pp 112–126Desantes JM, Salvador FJ, Carreres M, Jaramillo D (2015) Experimental characterization of the thermodynamic properties of diesel fuels over a wide range of pressures and temperatures. SAE Int J Fuels Lubr 8:2015-01-0951. https://doi.org/10.4271/2015-01-0951Bosch W (1966) The fuel rate indicator: a new measuring instrument for display of the characteristics of individual injection. SAE Pap. 660749Payri R, Salvador FJ, Gimeno J, Bracho G (2008) A new methodology for correcting the signal cumulative phenomenon on injection rate measurements. Exp Tech 32:46–49. https://doi.org/10.1111/j.1747-1567.2007.00188.xPayri F, Payri R, Salvador FJ, Martínez-López J (2011) A contribution to the understanding of cavitation effects in diesel injector nozzles through a combined experimental and computational investigation. Comput Fluids 58:88–101. https://doi.org/10.1016/j.compfluid.2012.01.005Lichtarowicz AK, Duggins RK, Markland E (1965) Discharge coefficients for incompressible non-cavitating flow through long orifices. J Mech Eng Sci 7:210–219. https://doi.org/10.1243/JMES_JOUR_1965_007_029_02Lopez JJ, Salvador FJ, De la Garza OA, Arrègle J (2012) Characterization of the pressure losses in a common rail diesel injector. Proc Inst Mech Eng D 226:1697–1706. https://doi.org/10.1177/0954407012447020Salvador FJ, Carreres M, Jaramillo D, Martínez-López J (2015) Comparison of microsac and VCO diesel injector nozzles in terms of internal nozzle flow characteristics. Energy Convers Manag 103:284–299. https://doi.org/10.1016/j.enconman.2015.05.062LMS (2010) Imagine.Lab AMESim v.10. User’s manualPayri R, Salvador FJ, Martí-Aldaraví P, Martínez-López J (2012) Using one-dimensional modeling to analyze the influence of the use of biodiesels on the dynamic behavior of solenoid-operated injectors in common rail systems: detailed injection system model. Energy Convers Manag 54:90–99. https://doi.org/10.1016/j.enconman.2011.10.00

Enhanced microbial bile acid deconjugation and impaired ileal uptake in pregnancy repress intestinal regulation of bile acid synthesis

Pregnancy is associated with progressive hypercholanemia, hypercholesterolemia, and hypertriglyceridemia, which can result in metabolic disease in susceptible women. Gut signals modify hepatic homeostatic pathways, linking intestinal content to metabolic activity. We sought to identify whether enteric endocrine signals contribute to raised serum bile acids observed in human and murine pregnancies, by measuring fibroblast growth factor (FGF) 19/15 protein and mRNA levels, and 7α-hydroxy-4-cholesten-3-one. Terminal ileal farnesoid X receptor (FXR)-mediated gene expression and apical sodium bile acid transporter (ASBT) protein concentration were measured by qPCR and western blotting. Shotgun whole-genome sequencing and ultra-performance liquid chromatography tandem mass spectrometry were used to determine the cecal microbiome and metabonome. Targeted and untargeted pathway analyses were performed to predict the systemic effects of the altered metagenome and metabolite profiles. Dietary CA supplementation was used to determine whether the observed alterations could be overcome by intestinal bile acids functioning as FXR agonists. Human and murine pregnancy were associated with reduced intestinal FXR signaling, with lower FGF19/15 and resultant increased hepatic bile acid synthesis. Terminal ileal ASBT protein was reduced in murine pregnancy. Cecal bile acid conjugation was reduced in pregnancy because of elevated bile salt hydrolase-producing Bacteroidetes. CA supplementation induced intestinal FXR signaling, which was not abrogated by pregnancy, with strikingly similar changes to the microbiota and metabonome as identified in pregnancy. Conclusion: The altered intestinal microbiota of pregnancy enhance bile acid deconjugation, reducing ileal bile acid uptake and lowering FXR induction in enterocytes. This exacerbates the effects mediated by reduced bile acid uptake transporters in pregnancy. Thus, in pregnant women and mice, there is reduced FGF19/15-mediated hepatic repression of hepatic bile acid synthesis, resulting in hypercholanemia

Loss of Nrf2 abrogates the protective effect of Keap1 down regulation in a preclinical model of cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinomas (cSCC) are the most common and highly mutated human malignancies, challenging identification of driver mutations and targeted therapies. Transcription factor NF-E2 p45-related factor 2 (Nrf2) orchestrates a cytoprotective inducible program, which counteracts the damaging effects of solar UV radiation, the main etiological factor in cSCC development. Downregulation of Kelch-like ECH-associated protein 1 (Keap1), a Cullin-3/Rbx1 ubiquitin ligase substrate adaptor protein, which mediates the ubiquitination and proteasomal degradation of Nrf2, has a strong protective effect in a preclinical model of cSCC. However, in addition to Nrf2, Keap1 affects ubiquitination of other proteins in the carcinogenesis process, including proteins involved in inflammation and DNA damage repair. Here, we generated Keap1(flox/flox) SKH-1 hairless mice in which Nrf2 is disrupted (Keap1(flox/flox)/Nrf2(−/−)) and subjected them chronically to solar-simulated UV radiation. We found that the incidence, multiplicity and burden of cSCC that form in Keap1(flox/flox)/Nrf2(−/−) mice are much greater than in their Keap1(flox/flox)/Nrf2(+/+) counterparts, establishing Nrf2 activation as the protection mediator. Our findings further imply that inhibition of Nrf2 globally, a strategy proposed for cancer treatment, is unlikely to be beneficial

Complementary intestinal mucosa and microbiota responses to caloric restriction

The intestine is key for nutrient absorption and for interactions between the microbiota and its host. Therefore, the intestinal response to caloric restriction (CR) is thought to be more complex than that of any other organ. Submitting mice to 25% CR during 14 days induced a polarization of duodenum mucosa cell gene expression characterised by upregulation, and downregulation of the metabolic and immune/inflammatory pathways, respectively. The HNF, PPAR, STAT, and IRF families of transcription factors, particularly the Pparα and Isgf3 genes, were identified as potentially critical players in these processes. The impact of CR on metabolic genes in intestinal mucosa was mimicked by inhibition of the mTOR pathway. Furthermore, multiple duodenum and faecal metabolites were altered in CR mice. These changes were dependent on microbiota and their magnitude corresponded to microbial density. Further experiments using mice with depleted gut bacteria and CR-specific microbiota transfer showed that the gene expression polarization observed in the mucosa of CR mice is independent of the microbiota and its metabolites. The holistic interdisciplinary approach that we applied allowed us to characterize various regulatory aspects of the host and microbiota response to CR

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses

Purpose: To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease.Methods: Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index.Results: Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p<0.05). Arterial reaction time was linked to serum creatinine (p=0.036) and eGFR (p=0.039), venous reaction time was linked to creatinine clearance (p=0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p<0.001 and p=0.003 respectively) and the dilatation amplitude (p=0.038 and p=0.048 respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p=0.004) and dilatation amplitude (p=0.017), vWf was linked to the maximum constriction response (p=0.016), and creatinine clearance to the baseline diameter fluctuation (p=0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p=0.022). Conclusions: Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses

Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women

Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways. Alterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-α-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue. VLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome