How to detect a counterfeit coin: Adaptive versus non-adaptive solutions

In an old weighing puzzle, there are n?3 coins that are identical in appearance. All the coins except one have the same weight, and that counterfeit one is a little bit lighter or heavier than the others, though it is not known in which direction. What is the smallest number of weighings needed to identify the counterfeit coin and to determine its type, using balance scales without measuring weights? This question was fully answered in 1946 by Dyson [The Mathematical Gazette 30 (1946) 231-234]. For values of n that are divisible by three, Dyson's scheme is non-adaptive and hence its later weighings do not depend on the outcomes of its earlier weighings. For values of n that are not divisible by three, however, Dyson's scheme is adaptive. In this note, we show that for all values n?3 there exists an optimal weighing scheme that is non-adaptive.     

Analysis of left ventricular wall motion based on volumetric deformable models and MRI-SPAMM

We present a new approach for the analysis of the left ventricular shape and motion based on the development of a new class of volumetric deformable models. We estimate the deformation and complex motion of the left ventricle (LV) in terms of a few parameters that are functions and whose values vary locally across the LV. These parameters capture the radial and longitudinal contraction, the axial twisting, and the long-axis deformation. Using Lagrangian dynamics and finite-element theory, we convert these volumetric primitives into dynamic models that deform due to forces exerted by the datapoints. We present experiments where we used magnetic tagging (MRI-SPAMM) to acquire datapoints from the LV during systole. By applying our method to MRI-SPAMM datapoints, we were able to characterize the 3-D shape and motion of the LV both locally and globally, in a clinically useful way. In addition, based on the model parameters we were able to extract quantitative differences between normal and abnormal hearts and visualize them in a way that is useful to physicians.     

Regulation and Release of Vasoactive Endoglin by Brain Endothelium in Response to Hypoxia/Reoxygenation in Stroke

In large vessel occlusion stroke, recanalization to restore cerebral perfusion is essential but not necessarily sufficient for a favorable outcome. Paradoxically, in some patients, reperfusion carries the risk of increased tissue damage and cerebral hemorrhage. Experimental and clinical data suggest that endothelial cells, representing the interface for detrimental platelet and leukocyte responses, likely play a crucial role in the phenomenon referred to as ischemia/reperfusion (I/R)-injury, but the mechanisms are unknown. We aimed to determine the role of endoglin in cerebral I/R-injury; endoglin is a membrane-bound protein abundantly expressed by endothelial cells that has previously been shown to be involved in the maintenance of vascular homeostasis. We investigated the expression of membranous endoglin (using Western blotting and RT-PCR) and the generation of soluble endoglin (using an enzyme-linked immunosorbent assay of cell culture supernatants) after hypoxia and subsequent reoxygenation in human non-immortalized brain endothelial cells. To validate these in vitro data, we additionally examined endoglin expression in an intraluminal monofilament model of permanent and transient middle cerebral artery occlusion in mice. Subsequently, the effects of recombinant human soluble endoglin were assessed by label-free impedance-based measurement of endothelial monolayer integrity (using the xCELLigence DP system) and immunocytochemistry. Endoglin expression is highly inducible by hypoxia in human brain endothelial monolayers in vitro, and subsequent reoxygenation induced its shedding. These findings were corroborated in mice during MCAO; an upregulation of endoglin was displayed in the infarcted hemispheres under occlusion, whereas endoglin expression was significantly diminished after transient MCAO, which is indicative of shedding. Of note is the finding that soluble endoglin induced an inflammatory phenotype in endothelial monolayers. The treatment of HBMEC with endoglin resulted in a decrease in transendothelial resistance and the downregulation of VE-cadherin. Our data establish a novel mechanism in which hypoxia triggers the initial endothelial upregulation of endoglin and subsequent reoxygenation triggers its release as a vasoactive mediator that, when rinsed into adjacent vascular beds after recanalization, can contribute to cerebral reperfusion injury.     

The Synchronous Approach to Designing Reactive Systems

Synchronous programming is available through several formally defined languages having very different characteristics: Esterel is imperative, while Lustre and Signal are declarative in style; Statecharts and Argos are graphical languages that allow one to program by constructing hierarchical automata. Our motivation for taking the synchronous design paradigm further, integrating imperative, declarative (or dataflow), and graphical programming styles, is that real systems typically have components that match each of these profiles. This paper motivates our interest in the mixed language programming of embedded software around a number of examples, and sketches the semantical foundation of the Synchronie toolset which ensures a coherent computational model. This toolset supports a design trajectory that incorporates rapid prototyping and systematic testing for early design validation, an object oriented development methodology for long term software management, and formal verification at the level of automatically generated object code.     

Tumor Infiltration with CD20+CD73+ B Cells Correlates with Better Outcome in Colorectal Cancer

Immunotherapy has become increasingly important in the treatment of colorectal cancer (CRC). Currently, CD73, also known as ecto-5′-nucleotidase (NT5E), has gained considerable interest as a potential therapeutic target. CD73 is one of the key enzymes catalyzing the conversion of extracellular ATP into adenosine, which in turn exerts potent immune suppressive effects. However, the role of CD73 expression on various cell types within the CRC tumor microenvironment remains unresolved. The expression of CD73 on various cell types has been described recently, but the role of CD73 on B-cells in CRC remains unclear. Therefore, we analyzed CD73 on B-cells, especially on tumor-infiltrating B-cells, in paired tumor and adjacent normal tissue samples from 62 eligible CRC patients. The highest expression of CD73 on tumor-infiltrating B-cells was identified on class-switched memory B-cells, followed by naive B-cells, whereas no CD73 expression was observed on plasmablasts. Clinicopathological correlation analysis revealed that higher CD73⁺ B-cells infiltration in the CRC tumors was associated with better overall survival. Moreover, metastasized patients showed a significantly decreased number of tumor-infiltrating CD73⁺ B-cells. Finally, neoadjuvant therapy correlated with reduced CD73⁺ B-cell numbers and CD73 expression on B-cells in the CRC tumors. As promising new immune therapies are being developed, the role of CD73⁺ B-cells and their subsets in the development of colorectal cancer should be further explored to find new therapeutic options.     

The Flexible Rare Event Sampling Harness System (FRESHS)

We present the software package FRESHS (http://www.freshs.org) for parallel simulation of rare events using sampling techniques from the ‘splitting’ family of methods. Initially, Forward Flux Sampling (FFS) and Stochastic Process Rare Event Sampling (SPRES) have been implemented. These two methods together make rare event sampling available for both quasi-static and full non-equilibrium regimes. Our framework provides a plugin system for software implementing the underlying physics of the system of interest. At present, example plugins exist for our framework to steer the popular MD packages GROMACS, LAMMPS and ESPResSo, but due to the simple interface of our plugin system, it is also easy to attach other simulation software or self-written code. Use of our framework does not require recompilation of the simulation program. The modular structure allows the flexible implementation of further sampling methods or physics engines and creates a basis for objective comparison of different sampling algorithms.     

Using organizational influence processes to overcome IS implementation barriers: lessons from a longitudinal case study of SPI implementation

A fundamental tenet of the information systems (IS) discipline holds that: (a) a lack of formal power and influence over the organization targeted for change, (b) weak support from top management, and (c) organizational memories of prior failures are barriers to implementation success. Our research, informed by organization influence, compellingly illustrates that such conditions do not necessarily doom a project to failure. In this paper, we present an analysis of how an IS implementation team designed and enacted a coordinated strategy of organizational influence to achieve implementation success despite these barriers. Our empirical analysis also found that technology implementation and change is largely an organizational influence process (OIP), and thus technical-rational approaches alone are inadequate for achieving success. Our findings offer managers important insights into how they can design and enact OIPs to effectively manage IS implementation. Further, we show how the theory of organizational influence can enhance understanding of IS implementation dynamics and advance the development of a theory of effective IS change agentry.     

Comparative characterization of particle emissions from asbestos and non-asbestos cement roof slates

The first aim of this study was to characterise total and size-fractionated particulate matter (PM) aerosol, including fibres, released from the processing operations of cement roofing slates. The second aim was to compare particle emissions from asbestos-cement and non-asbestos cement sheets, with respect to total and size-fractionated particulate matter as well as fibres emissions. Asbestos and cellulose-based cement sheets were compared during slate treatment processes, namely crushing, rubbing, rasping and scrubbing. Generated PM and fibres were classified by a variety of methods (PM_2.5 and PM₁₀ cyclones, aerodynamic particle spectrometer and optical particle counter). A substantial variation in the mass of generated particles has been noticed, both within each PM fraction and between different treatment processes. The PM₁₀/PM_total concentration ratio ranged from 70 to 98% and PM_2.5/PM_total ratio equalled to ∼20%. The new generation non-asbestos sheets produced three times higher PM emissions than asbestos-cement sheets during crushing operation. Particle size distribution of number concentrations was mostly bimodal (two modes at 0.5 and 2.5 μm). With respect to fibres, the release of cellulose fibres from non-asbestos slates was from 1.8 to 13 times lower in comparison with asbestos fibres. At the same time, cellulose fibre length was 1.4–1.6 times lower. Hence, new generation non-asbestos roofing slates were proved to be less hazardous from the point of view of fibre release, but more hazardous with respect to total particle release.