Methodologies for Designing Power-Aware Smart Card Systems

Smart cards are some of the smallest computing platforms in use today. They have limited resources, but a huge number of functional requirements. The requirement for multi-application cards increases the demand for high performance and security even more, whereas the limits given by size and energy consumption remain constant. We describe new methodologies for designing and implementing entire systems with regard to power awareness and required performance. To make use of this power-saving potential, also the higher layers of the system - the operating system layer and the application domain layer - are required to be designed together with the rest of the system. HW/SW co-design methodologies enable the gain of system-level optimization. The first part presents the abstraction of smart cards to optimize system architecture and memory system. Both functional and transactional-level models are presented and discussed. The proposed design flow and preliminary results of the evaluation are depicted. Another central part of this methodology is a cycle-accurate instruction-set simulator for secure software development. The underlaying energy model is designed to decouple instruction and data dependent energy dissipation, which leads to an independent characterization process and allows stepwise model refinement to increase estimation accuracy. The model has been evaluated for a high-performance smart card CPU and an use-case for secure software is given

Identification of the mitochondrial receptor complex in Saccharomyces cerevisiae

Mitochondrial protein import involves the recognition of preproteins by receptors and their subsequent translocation across the outer membrane. In Neurospora crassa, the two import receptors, MOM19 and MOM72, were found in a complex with the general insertion protein, GIP (formed by MOM7, MOM8, MOM30 and MOM38) and MOM22. We isolated a complex out of S. cerevisiae mitochondria consisting of MOM38/ISP42, the receptor MOM72, and five new yeast proteins, the putative equivalents of N. crassa MOM7, MOM8, MOM19, MOM22 and MOM30. A receptor complex isolated out of yeast cells transformed with N. crassa MOM19 contained the N. crassa master receptor in addition to the yeast proteins. This demonstrates that the yeast complex is functional, and provides strong evidence that we also have identified the yeast MOM19

Import of ADP/ATP carrier into mitochondria

We have identified the yeast homologue of Neurospora crassa MOM72, the mitochondrial import receptor for the ADP/ATP carrier (AAC), by functional studies and by cDNA sequencing. Mitochondria of a yeast mutant in which the gene for MOM72 was disrupted were impaired in specific binding and import of AAC. Unexpectedly, we found a residual, yet significant import of AAC into mitochondria lacking MOM72 that occurred via the receptor MOM19. We conclude that both MOM72 and MOM19 can direct AAC into mitochondria, albeit with different efficiency. Moreover, the precursor of MOM72 apparently does not require a positively charged sequence at the extreme amino terminus for targeting to mitochondria

Integrative genomic analysis of CREB defines a critical role for transcription factor networks in mediating the fed/fasted switch in liver

BACKGROUND: Metabolic homeostasis in mammals critically depends on the regulation of fasting-induced genes by CREB in the liver. Previous genome-wide analysis has shown that only a small percentage of CREB target genes are induced in response to fasting-associated signaling pathways. The precise molecular mechanisms by which CREB specifically targets these genes in response to alternating hormonal cues remain to be elucidated. RESULTS: We performed chromatin immunoprecipitation coupled to high-throughput sequencing of CREB in livers from both fasted and re-fed mice. In order to quantitatively compare the extent of CREB-DNA interactions genome-wide between these two physiological conditions we developed a novel, robust analysis method, termed the ‘single sample independence’ (SSI) test that greatly reduced the number of false-positive peaks. We found that CREB remains constitutively bound to its target genes in the liver regardless of the metabolic state. Integration of the CREB cistrome with expression microarrays of fasted and re-fed mouse livers and ChIP-seq data for additional transcription factors revealed that the gene expression switches between the two metabolic states are associated with co-localization of additional transcription factors at CREB sites. CONCLUSIONS: Our results support a model in which CREB is constitutively bound to thousands of target genes, and combinatorial interactions between DNA-binding factors are necessary to achieve the specific transcriptional response of the liver to fasting. Furthermore, our genome-wide analysis identifies thousands of novel CREB target genes in liver, and suggests a previously unknown role for CREB in regulating ER stress genes in response to nutrient influx

ICON in Climate Limited-area Mode (ICON release version 2.6.1): a new regional climate model

For the first time, the Limited-Area Mode of the new ICON (Icosahedral Nonhydrostatic) weather and climate model has been used for a continuous long-term regional climate simulation over Europe. Built upon the Limited-Area Mode of ICON (ICON-LAM), ICON-CLM (ICON in Climate Limited-area Mode, hereafter ICON-CLM, available in ICON release version 2.6.1) is an adaptation for climate applications. A first version of ICON-CLM is now available and has already been integrated into a starter package (ICON-CLM_SP_betal). The starter package provides users with a technical infrastructure that facilitates long-term simulations as well as model evaluation and test routines. ICON-CLM and ICON-CLM_SP were successfully installed and tested on two different computing systems. Tests with different domain decompositions showed bit-identical results, and no systematic outstanding differences were found in the results with different model time steps. ICON-CLM was also able to reproduce the large-scale atmospheric information from the global driving model. Comparison was done between ICON-CLM and the COnsortium for Small-scale MOdeling (COSMO)-CLM (the recommended model configuration by the CLM-Community) performance. For that, an evaluation run of ICON-CLM with ERA-Interim boundary conditions was carried out with the setup similar to the COSMO-CLM recommended optimal setup. ICON-CLM results showed biases in the same range as those of COSMO-CLM for all evaluated surface variables. While this COSMO-CLM simulation was carried out with the latest model version which has been developed and was carefully tuned for climate simulations on the European domain, ICON-CLM was not tuned yet. Nevertheless, ICON-CLM showed a better performance for air temperature and its daily extremes, and slightly better performance for total cloud cover. For precipitation and mean sea level pressure, COSMO-CLM was closer to observations than ICON-CLM. However, as ICON-CLM is still in the early stage of development, there is still much room for improvement

COSMO-CLM regional climate simulations in the Coordinated Regional Climate Downscaling Experiment (CORDEX) framework: a review

In the last decade, the Climate Limited-area Modeling Community (CLM-Community) has contributed to the Coordinated Regional Climate Downscaling Experiment (CORDEX) with an extensive set of regional climate simulations. Using several versions of the COSMO-CLM-Community model, ERA-Interim reanalysis and eight global climate models from phase 5 of the Coupled Model Intercomparison Project (CMIP5) were dynamically downscaled with horizontal grid spacings of 0.44∘ (∼ 50 km), 0.22∘ (∼ 25 km), and 0.11∘ (∼ 12 km) over the CORDEX domains Europe, South Asia, East Asia, Australasia, and Africa. This major effort resulted in 80 regional climate simulations publicly available through the Earth System Grid Federation (ESGF) web portals for use in impact studies and climate scenario assessments. Here we review the production of these simulations and assess their results in terms of mean near-surface temperature and precipitation to aid the future design of the COSMO-CLM model simulations. It is found that a domain-specific parameter tuning is beneficial, while increasing horizontal model resolution (from 50 to 25 or 12 km grid spacing) alone does not always improve the performance of the simulation. Moreover, the COSMO-CLM performance depends on the driving data. This is generally more important than the dependence on horizontal resolution, model version, and configuration. Our results emphasize the importance of performing regional climate projections in a coordinated way, where guidance from both the global (GCM) and regional (RCM) climate modeling communities is needed to increase the reliability of the GCM–RCM modeling chain

Prediction of human drug-induced liver injury (DILI) in relation to oral doses and blood concentrations

Drug-induced liver injury (DILI) cannot be accurately predicted by animal models. In addition, currently available in vitro methods do not allow for the estimation of hepatotoxic doses or the determination of an acceptable daily intake (ADI). To overcome this limitation, an in vitro/in silico method was established that predicts the risk of human DILI in relation to oral doses and blood concentrations. This method can be used to estimate DILI risk if the maximal blood concentration (Cmax) of the test compound is known. Moreover, an ADI can be estimated even for compounds without information on blood concentrations. To systematically optimize the in vitro system, two novel test performance metrics were introduced, the toxicity separation index (TSI) which quantifies how well a test differentiates between hepatotoxic and non-hepatotoxic compounds, and the toxicity estimation index (TEI) which measures how well hepatotoxic blood concentrations in vivo can be estimated. In vitro test performance was optimized for a training set of 28 compounds, based on TSI and TEI, demonstrating that (1) concentrations where cytotoxicity first becomes evident in vitro (EC10) yielded better metrics than higher toxicity thresholds (EC50); (2) compound incubation for 48 h was better than 24 h, with no further improvement of TSI after 7 days incubation; (3) metrics were moderately improved by adding gene expression to the test battery; (4) evaluation of pharmacokinetic parameters demonstrated that total blood compound concentrations and the 95%-population-based percentile of Cmax were best suited to estimate human toxicity. With a support vector machine-based classifier, using EC10 and Cmax as variables, the cross-validated sensitivity, specificity and accuracy for hepatotoxicity prediction were 100, 88 and 93%, respectively. Concentrations in the culture medium allowed extrapolation to blood concentrations in vivo that are associated with a specific probability of hepatotoxicity and the corresponding oral doses were obtained by reverse modeling. Application of this in vitro/in silico method to the rat hepatotoxicant pulegone resulted in an ADI that was similar to values previously established based on animal experiments. In conclusion, the proposed method links oral doses and blood concentrations of test compounds to the probability of hepatotoxicity