Transfer Function Synthesis without Quantifier Elimination

Traditionally, transfer functions have been designed manually for each operation in a program, instruction by instruction. In such a setting, a transfer function describes the semantics of a single instruction, detailing how a given abstract input state is mapped to an abstract output state. The net effect of a sequence of instructions, a basic block, can then be calculated by composing the transfer functions of the constituent instructions. However, precision can be improved by applying a single transfer function that captures the semantics of the block as a whole. Since blocks are program-dependent, this approach necessitates automation. There has thus been growing interest in computing transfer functions automatically, most notably using techniques based on quantifier elimination. Although conceptually elegant, quantifier elimination inevitably induces a computational bottleneck, which limits the applicability of these methods to small blocks. This paper contributes a method for calculating transfer functions that finesses quantifier elimination altogether, and can thus be seen as a response to this problem. The practicality of the method is demonstrated by generating transfer functions for input and output states that are described by linear template constraints, which include intervals and octagons.Comment: 37 pages, extended version of ESOP 2011 pape

Climate variability in SE Europe since 1450 AD based on a varved sediment record from Etoliko Lagoon (Western Greece)

To achieve deeper understanding of climate variability during the last millennium in SE Europe, we report new sedimentological and paleoecological data from Etoliko Lagoon, Western Greece. The record represents the southernmost annually laminated (i.e., varved) archive from the Balkan Peninsula spanning the Little Ice Age, allowing insights into critical time intervals of climate instability such as during the Maunder and Dalton solar minima. After developing a continuous, ca. 500-year-long varve chronology, high-resolution μ–XRF counts, stable-isotope data measured on ostracod shells, palynological (including pollen and dinoflagellate cysts), and diatom data are used to decipher the season-specific climate and ecosystem evolution at Etoliko Lagoon since 1450 AD. Our results show that the Etoliko varve record became more sensitive to climate change from 1740 AD onwards. We attribute this shift to the enhancement of primary productivity within the lagoon, which is documented by an up to threefold increase in varve thickness. This marked change in the lagoon's ecosystem was caused by: (i) increased terrestrial input of nutrients, (ii) a closer connection to the sea and human eutrophication particularly from 1850 AD onwards, and (iii) increasing summer temperatures. Integration of our data with those of previously published paleolake sediment records, tree-ring-based precipitation reconstructions, simulations of atmospheric circulation and instrumental precipitation data suggests that wet conditions in winter prevailed during 1740–1790 AD, whereas dry winters marked the periods 1790–1830 AD (Dalton Minimum) and 1830–1930 AD, the latter being sporadically interrupted by wet winters. This variability in precipitation can be explained by shifts in the large-scale atmospheric circulation patterns over the European continent that affected the Balkan Peninsula (e.g., North Atlantic Oscillation). The transition between dry and wet phases at Etoliko points to longitudinal shifts of the precipitation pattern in the Balkan Peninsula during the Little Ice Age

Язык и мировая культура: взгляд молодых исследователей. Ч. 1

Настоящий сборник объединяет исследовательские проекты аспирантов и преподавателей языковых кафедр и содержит материалы, представляющие широкий круг научно-учебных интересов в парадигме современных гуманитарных знаний, и включает, в основном, вопросы теории и практики преподавания иностранных языков. Сборник адресован аспирантам и преподавателям, а также всем, кого интересует теория и методика профессионального образования, методика обучения иностранным языкам, изучение языков в их взаимосвязи с философией, литературой, историей и культурой

Automated analysis of acetaminophen toxicity on 3D HepaRG cell culture in microbioreactor

Real-time monitoring of bioanalytes in organotypic cell cultivation devices is a major research challenge in establishing stand-alone diagnostic systems. Presently, no general technical facility is available that offers a plug-in system for bioanalytics in diversely available organotypic culture models. Therefore, each analytical device has to be tuned according to the microfluidic and interface environment of the 3D in vitro system. Herein, we report the design and function of a 3D automated culture and analysis device (3D-ACAD) which actively perfuses a custom-made 3D microbioreactor, samples the culture medium and simultaneously performs capillary-based flow ELISA. A microstructured MatriGrid ® has been explored as a 3D scaffold for culturing HepaRG cells, with albumin investigated as a bioanalytical marker using flow ELISA. We investigated the effect of acetaminophen (APAP) on the albumin secretion of HepaRG cells over 96 h and compared this with the albumin secretion of 2D monolayer HepaRG cultures. Automated on-line monitoring of albumin secretion in the 3D in vitro mode revealed that the application of hepatotoxic drug-like APAP results in decreased albumin secretion. Furthermore, a higher sensitivity of the HepaRG cell culture in the automated 3D-ACAD system to APAP was observed compared to HepaRG cells cultivated as a monolayer. The results support the use of the 3D-ACAD model as a stand-alone device, working in real time and capable of analyzing the condition of the cell culture by measuring a functional analyte. Information obtained from our system is compared with conventional cell culture and plate ELISA, the results of which are presented herein