HiGate (High Grade Anti-Tamper Equipment) Prototype and Application to e-Discovery

These days, most data is digitized and processed in various ways by computers. In the past, computer owners were free to process data as desired and to observe the inputted data as well as the interim results. However, the unrestricted processing of data and accessing of interim results even by computer users is associated with an increasing number of adverse events. These adverse events often occur when sensitive data such as personal or confidential business information must be handled by two or more parties, such as in the case of e-Discovery, used in legal proceedings, or epidemiologic studies. To solve this problem, providers encrypt data, and the owner of the computer performs decoding in the memory for encrypted data. The computer owner can be limited to performing only certain processing of data and to observing only the final results. As an implementation that uses existing technology to realize this solution, the processing of data contained in a smart card was considered, but such an implementation would not be practical due to issues related to computer capacity and processing speed. Accordingly, the authors present the concept of PC-based High Grade AntiTamper Equipment (HiGATE), which allows data to be handled without revealing the data content to administrators or users. To verify this concept, an eDiscovery application on a prototype was executed and the results are reported here

Complete Genome Sequencing of a Community-Associated Methicillin-Resistant Staphylococcus aureus ψUSA300 Strain JICS127, a Uniquely Evolved USA300 Lineage in Japan

A ψUSA300 clone of MRSA, a derivative of USA300, is uniquely found in Japan and has 12-bp deletion on ccrB2 in type IVa staphylococcal cassette chromosome mec element. We hereby present the complete genome of ψUSA300 strain JICS127

HiGate (High Grade Anti‐Tamper Equipment) Prototype and Application to e‐Discovery

These days, most data is digitized and processed in various ways by computers. In the past, computer owners were free to process data as desired and to observe the inputted data as well as the interim results. However, the unrestricted processing of data and accessing of interim results even by computer users is associated with an increasing number of adverse events. These adverse events often occur when sensitive data such as personal or confidential business information must be handled by two or more parties, such as in the case of e-Discovery, used in legal proceedings, or epidemiologic studies. To solve this problem, providers encrypt data, and the owner of the computer performs decoding in the memory for encrypted data. The computer owner can be limited to performing only certain processing of data and to observing only the final results. As an implementation that uses existing technology to realize this solution, the processing of data contained in a smart card was considered, but such an implementation would not be practical due to issues related to computer capacity and processing speed. Accordingly, the authors present the concept of PC-based High Grade Anti-Tamper Equipment (HiGATE), which allows data to be handled without revealing the data content to administrators or users. To verify this concept, an e-Discovery application on a prototype was executed and the results are reported here. Keyword: Anti-Tamper, e-Discovery, Bitlocker, APIHoo

A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl4)-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl4 (0.2 ml/kg 2×wk/6wks) followed by alcohol intragastrically (up to 25 g/kg/day for 3wks) and with continued CCl4. We observed that combined treatment with CCl4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for 53 damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Harcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways

Regulation of the unfolded protein response via S-nitrosylation of sensors of endoplasmic reticulum stress

Protein S-nitrosylation modulates important cellular processes, including neurotransmission, vasodilation, proliferation, and apoptosis in various cell types. We have previously reported that protein disulfide isomerase (PDI) is S-nitrosylated in brains of patients with sporadic neurodegenerative diseases. This modification inhibits PDI enzymatic activity and consequently leads to the accumulation of unfolded/misfolded proteins in the endoplasmic reticulum (ER) lumen. Here, we describe S-nitrosylation of additional ER pathways that affect the unfolded protein response (UPR) in cell-based models of Parkinson's disease (PD). We demonstrate that nitric oxide (NO) can S-nitrosylate the ER stress sensors IRE1α and PERK. While S-nitrosylation of IRE1α inhibited its ribonuclease activity, S-nitrosylation of PERK activated its kinase activity and downstream phosphorylation/inactivation or eIF2α. Site-directed mutagenesis of IRE1α(Cys931) prevented S-nitrosylation and inhibition of its ribonuclease activity, indicating that Cys931 is the predominant site of S-nitrosylation. Importantly, cells overexpressing mutant IRE1α(C931S) were resistant to NO-induced damage. Our findings show that nitrosative stress leads to dysfunctional ER stress signaling, thus contributing to neuronal cell death

IMPLEMENTING BOOT CONTROL FOR WINDOWS VISTA

Abstract A digital forensic logging system must prevent the booting of unauthorized programs and the modification of evidence. Our previous research developed Dig-Force2, a boot control system for Windows XP platforms that employs API hooking and a trusted platform module. However, Dig-Force2 cannot be used for Windows Vista systems because the hooked API cannot monitor booting programs in user accounts. This paper describes an enhanced version of Dig-Force2, which uses a TPM and a white list to provide boot control functionality for Windows Vista systems. In addition, the paper presents the results of security and performance evaluations of the boot control system

Verdet constant dispersion of magnesium fluoride for deep-ultraviolet and vacuum-ultraviolet Faraday rotators

The Verdet constant dispersion in magnesium fluoride (MgF2) crystals was evaluated over a wavelength range of 190–300 nm. The Verdet constant was found to be 38.7 rad/(T·m) at a wavelength of 193 nm. These results were fitted using the diamagnetic dispersion model and the classical Becquerel formula. The fitted results can be used for the designing of suitable Faraday rotators at various wavelengths. These results indicate the possibility of using MgF2 as Faraday rotators not only in deep-ultraviolet regions, but also in vacuum-ultraviolet regions owing to its large bandgap

Necroptosis and acute pancreatitis

The sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3-/- or Mlkl-/- mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3-/- mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl-/- mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl-/- mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment

A Zebrafish Chemical Suppressor Screening Identifies Small Molecule Inhibitors of the Wnt/β-catenin Pathway

SummaryGenetic screening for suppressor mutants has been successfully used to identify important signaling regulators. Using an analogy to genetic suppressor screening, we developed a chemical suppressor screening method to identify inhibitors of the Wnt/β-catenin signaling pathway. We used zebrafish embryos in which chemically induced β-catenin accumulation led to an “eyeless” phenotype and conducted a pilot screening for compounds that restored eye development. This approach allowed us to identify geranylgeranyltransferase inhibitor 286 (GGTI-286), a geranylgeranyltransferase (GGTase) inhibitor. Our follow-up studies showed that GGTI-286 reduces nuclear localization of β-catenin and transcription dependent on β-catenin/T cell factor in mammalian cells. In addition to pharmacological inhibition, GGTase gene knockdown also attenuates the nuclear function of β-catenin. Overall, we validate our chemical suppressor screening as a method for identifying Wnt/β-catenin pathway inhibitors and implicate GGTase as a potential therapeutic target for Wnt-activated cancers

Effect of erbium concentration on the Verdet constant dispersion of LiY1.0-xErxF4 single crystal

The dispersion of the Verdet constant of LiY1.0-xErxF4 crystals was evaluated from 190 nm to 500 nm for different doping concentrations of Er ions. A 15% doping concentration yielded a high Verdet constant of 54.5 rad/(T·m) at 193 nm. This value can be explained by the contribution of the diamagnetic term associated with LiYF4 and the paramagnetic term of the Er ions. Although the LiYF4 crystal yielded a lower value of −36.6 rad/(T·m) at 193 nm from Er-doped LiYF4, it can be used in the vacuum–ultraviolet region because of its high transmittance at wavelengths longer than 120 nm