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Implications of False Alarms in Dynamic Games on Cyber-Security
No full textCyber-threats including computer viruses, data breaches, and denial-of-service attacks have become increasingly prevalent and need to be handled effectively. Imperfect prevention of cyber-attacks inevitably results in false alarms from the defense system. We consider a dynamic game in which a defender operating an intrusion detection system is penalized for false alarms. By characterizing the equilibrium of the game, we search for the implications of false alarms under various circumstances. Specifically, we consider the cyber-insurance market, operational risk, and government intervention. Our model shows that both demand and supply of cyber-insurance can be low, which explains the underdevelopment of the cyber-insurance market. The analysis of an extended model with operational risk shows that reducing the operational risk decreases the cyber-risks but increases the false alarm rate. Regarding government intervention, we suggest a simple policy that achieves a socially optimal outcome
An ANN-assisted efficient enriched finite element method via the selective enrichment of moment fitting
No full textEnrichment techniques that employ nonconforming mesh are effective in modeling structures with discontinuities because numerical issues regarding mesh quality are avoided. However, the accurate integration of the bilinear and linear forms on the discretized domain, which is required in the standard Galerkin-based finite element method, is computationally expensive due to the complexity of the enriched basis function. In this paper, we present a fast and accurate alternative method of numerical integration using nonlinear regression enabled by a multi-perceptron feedforward neural network. The relationship between an implicitly represented geometry and the quadrature rule derived from the moment fitting method is predicted by the neural network; the neural network-based regression model circumvents complex computation and significantly reduces the overall online time by avoiding expensive function evaluations. Through the selected numerical examples, we demonstrate the efficiency and accuracy of the current method, as well as the flexibility of the trained network to be used in different contexts
Directing battery chemistry using side-view operando optical microscopy
No full textThis review highlights recent progress and perspectives on side-view operando optical microscopy (OM) on lithium-ion batteries (LIBs). Side-view operando imaging studies on LIBs offer new insights for understanding the dynamic feature of battery chemistry since the images or movies offer direct visualization of the most realistic conditions. Taking advantage of a fundamentally complete understanding, we have a chance to overcome the formidable challenges of the LIBs. For the realistic demonstration of each part of the battery components, OM has been used to understand direct electrochemical reactions identifying the fundamental failure mechanisms that help overcome the challenges of LIBs. Here, we provide a comprehensive review of our research work in the field of the application of OM for understanding the various challenging aspects of LIBs. Moreover, we highlight that the further utilization of the OM technique towards and beyond the LIBs could lead to the development of next-generation batteries
Optimal Investment in an Illiquid Market with Search Frictions and Transaction Costs
No full textWe consider an optimal investment problem to maximize expected utility of the terminal wealth, in an illiquid market with search frictions and transaction costs. In the market model, an investor???s attempt of transaction is successful only at arrival times of a Poisson process, and the investor pays proportional transaction costs when the transaction is successful. We characterize the no-trade region describing the optimal trading strategy. Our asymptotic analysis implies that the effects of the transaction costs are more pronounced (more widening effect of the no-trade region and more diminishing effect of the value function) in the market with less search frictions
Inducible disruption of Tet genes results in myeloid malignancy, readthrough transcription, and a heterochromatin-to-euchromatin switch
No full textThe three mammalian TET dioxygenases oxidize the methyl group of 5-methylcytosine in DNA, and the oxidized methylcytosines are essential intermediates in all known pathways of DNA demethylation. To define the in vivo consequences of complete TET deficiency, we inducibly deleted all three Tet genes in the mouse genome. Tet1/2/3-inducible TKO (iTKO) mice succumbed to acute myeloid leukemia (AML) by 4 to 5 wk. Single-cell RNA sequencing of Tet iTKO bone marrow cells revealed the appearance of new myeloid cell populations characterized by a striking increase in expression of all members of the stefin/cystatin gene cluster on mouse chromosome 16. In patients with AML, high stefin/cystatin gene expression correlates with poor clinical outcomes. Increased expression of the clustered stefin/cystatin genes was associated with a heterochromatin-to-euchromatin compartment switch with readthrough transcription downstream of the clustered stefin/cystatin genes as well as other highly expressed genes, but only minor changes in DNA methylation. Our data highlight roles for TET enzymes that are distinct from their established function in DNA demethylation and instead involve increased transcriptional readthrough and changes in three-dimensional genome organization
Epigenetic regulation of Neuregulin 1 promotes breast cancer progression associated to hyperglycemia
No full textHyperglycemia is a risk factor for breast cancer-related morbidity and mortality. Hyperglycemia induces Neuregulin 1 (Nrg1) overexpression in breast cancer, which subsequently promotes tumor progression. However, molecular mechanisms underlying hyperglycemia-induced Nrg1 overexpression remain poorly understood. Here, we show that hyperglycemia causes active histone modifications at the Nrg1 enhancer, forming enhanceosome complexes where recombination signal binding protein for immunoglobulin kappa J region (RBPJ), E1A binding protein p300 (P300), and SET domain containing 1???A (SETD1A) are recruited to upregulate Nrg1 expression. Deletions in RBPJ-binding sites causes hyperglycemia-controlled Nrg1 levels to be downregulated, resulting in decreased tumor growth in vitro and in vivo. Mice with modest-temporary hyperglycemia, induced by low-dose short-exposure streptozotocin, display accelerated tumor growth and lapatinib resistance, whereas combining lapatinib with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S42 phenylglycine t-butyl ester (DAPT) ameliorates tumor growth under these modest hyperglycemic conditions by inhibiting NOTCH and EGFR superfamilies. NOTCH activity is correlated with NRG1 levels, and high NRG1 levels predicts poor outcomes, particularly in HER2-positive breast cancer patients. Our findings highlight the hyperglycemia-linked epigenetic modulation of NRG1 as a potential therapeutic strategy for treating breast cancer patients with diabetes
Epigenetic Modification of Cytosines in Hematopoietic Differentiation and Malignant Transformation
No full textThe mammalian DNA methylation landscape is established and maintained by the combined activities of the two key epigenetic modifiers, DNA methyltransferases (DNMT) and Ten-eleven-translocation (TET) enzymes. Once DNMTs produce 5-methylcytosine (5mC), TET proteins fine-tune the DNA methylation status by consecutively oxidizing 5mC to 5-hydroxymethylcytosine (5hmC) and further oxidized derivatives. The 5mC and oxidized methylcytosines are essential for the maintenance of cellular identity and function during differentiation. Cytosine modifications with DNMT and TET enzymes exert pleiotropic effects on various aspects of hematopoiesis, including self-renewal of hematopoietic stem/progenitor cells (HSPCs), lineage determination, differentiation, and function. Under pathological conditions, these enzymes are frequently dysregulated, leading to loss of function. In particular, the loss of DNMT3A and TET2 function is conspicuous in diverse hematological disorders, including myeloid and lymphoid malignancies, and causally related to clonal hematopoiesis and malignant transformation. Here, we update recent advances in understanding how the maintenance of DNA methylation homeostasis by DNMT and TET proteins influences normal hematopoiesis and malignant transformation, highlighting the potential impact of DNMT3A and TET2 dysregulation on clonal dominance and evolution of pre-leukemic stem cells to full-blown malignancies. Clarification of the normal and pathological functions of DNA-modifying epigenetic regulators will be crucial to future innovations in epigenetic therapies for treating hematological disorders
Optimization and application of passive air sampling method for gaseous elemental mercury in Ulsan, South Korea
No full textWe compared uptake rates and concentrations of gaseous elemental mercury (GEM) by passive sampling conditions and investigated the spatial distribution of GEM in Ulsan, the largest industrial city in South Korea. For the optimization of sampling conditions, two outer sampling containers (cylindrical polyethylene terephthalate and two stainless steel bowls), two different sulfur contents of the sorbent (16.3% and 26.3%), and three sampling periods (1, 2, and 3 months) were considered. The uptake rates of GEM were not statistically different by the sampling container, but they were increased with the sulfur contents of activated carbon. A sampling condition using two stainless bowls and lower sulfur contents of activated carbon for 2-3 months was preferred with the highest precision of GEM concentrations. With the same method, passive air samples were collected for 3 months in duplicate from 10 sites in Ulsan. The concentrations of GEM ranged from 3.13 to 11.2 ng/m(3) (mean 4.65 ng/m(3)), and the highest concentration was measured at a non-ferrous industrial complex. A zinc smelter in the non-ferrous industrial complex was identified as a major mercury source in Ulsan. This study is the first passive air sampling study investigating the spatial distributions of GEM in different types of industrial areas as well as residential areas of Ulsan
