Carbon Chain Length Modulates MDA-MB-231 Breast Cancer Cell Killing Mechanisms by Mitochondrially Targeted Aryl−Urea Fatty Acids

Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl−urea fatty acid ( 1 g ; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl−ureas the present study evaluated mitochondrial targeting by 1 g analogues containing alkyl chains between 10–17 carbons. Using the dye JC-1, the C12−C17 analogues efficiently disrupted the mitochondrial membrane potential (IC₅₀s 3.5±1.2 to 7.6±1.1 μM) and impaired ATP production; shorter analogues were less active. 7-Aminoactinomycin D/annexin V staining and flow cytometry showed that these agents activated the killing mechanisms of necrosis and apoptosis to varying extents (7-aminoactinomycin D/annexin V staining ratios 4.3–6.0). Indeed, 1 g and its C17 analogue preferentially activated necrosis and apoptosis, respectively (ratios 2.1 and 16). Taken together, alkyl chain length is a determinant of mitochondrial targeting by aryl−ureas and can be varied to develop analogues that activate apoptosis or necrosis in a regulated fashion.     

Types and associated type families for hardware simulation and synthesis

In this article we overview the design and implementation of the second generation of Kansas Lava. Driven by the needs and experiences of implementing telemetry decoders and other circuits, we have made a number of improvements to both the external API and the internal representations used. We have retained our dual shallow/deep representation of signals in general, but now have a number of externally visible abstractions for combinatorial and sequential circuits, and enabled signals. We introduce these abstractions, as well as our abstractions for reading and writing memory. Internally, we found the need to represent unknown values inside our circuits, so we made aggressive use of associated type families to lift our values to allow unknowns, in a principled and regular way. We discuss this design decision, how it unfortunately complicates the internals of Kansas Lava, and how we mitigate this complexity. Finally, when connecting Kansas Lava to the real world, the standardized idiom of using named input and output ports is provided by Kansas Lava using a new monad, called Fabric. We present the design of this Fabric monad, and illustrate its use in a small but complete example.     

MET𝔸P: revisiting Privacy-Preserving Data Publishing using secure devices

The goal of Privacy-Preserving Data Publishing (PPDP) is to generate a sanitized (i.e. harmless) view of sensitive personal data (e.g. a health survey), to be released to some agencies or simply the public. However, traditional PPDP practices all make the assumption that the process is run on a trusted central server. In this article, we argue that the trust assumption on the central server is far too strong. We propose Met _??P, a generic fully distributed protocol, to execute various forms of PPDP algorithms on an asymmetric architecture composed of low power secure devices and a powerful but untrusted infrastructure. We show that this protocol is both correct and secure against honest-but-curious or malicious adversaries. Finally, we provide an experimental validation showing that this protocol can support PPDP processes scaling up to nation-wide surveys.     

The multi-agent programming contest from 2005–2010

The Multi-Agent Programming Contest is an annual international event on programming multi-agent systems: Teams of agents participate in a simulated cooperative scenario. It started in 2005 and is organised in 2010 for the sixth time. The contest is an attempt to stimulate research in the area of multi-agent system development and programming by (i) identifying key problems in the field and (ii) collecting suitable benchmarks that can serve as milestones for testing multi-agent programming languages, platforms and tools. This article provides a short history of the contest since it started and reports in more detail on the cows and cowboys scenario implemented for the 2008, 2009 and 2010 contest editions. We briefly discuss the underlying technological background and conclude with a critical discussion of the experiences and lessons learned.     

Automatic computation of pebble roundness using digital imagery and discrete geometry

The shape of sedimentary particles is an important property, from which geographical hypotheses related to abrasion, distance of transport, river behavior, etc. can be formulated. In this paper, we use digital image analysis, especially discrete geometry, to automatically compute some shape parameters such as roundness, i.e. a measure of how much the corners and edges of a particle have been worn away.In contrast to previous work in which traditional digital images analysis techniques, such as Fourier transform, are used, we opted for a discrete geometry approach that allowed us to implement Wadell's original index, which is known to be more accurate, but more time consuming to implement in the field.Our implementation of Wadell's original index is highly correlated (92%) with the roundness classes of Krumbein's chart, used as a ground-truth. In addition, we show that other geometrical parameters, which are easier to compute, can be used to provide good approximations of roundness.We also used our shape parameters to study a set of pebbles digital images taken from the Progo basin river network (Indonesia). The results we obtained are in agreement with previous work and open new possibilities for geomorphologists thanks to automatic computation.     

Model checking multi-agent systems with logic based Petri nets

We introduce a class of Petri nets, simple logic Petri nets (SLPN), that are based on logical expressions. We show how this type of nets can be efficiently mapped into logic programs with negation: the corresponding answer sets describe interleaved executions of the underlying nets (Theorem 1). The absence of an answer set indicates a deadlock situation. We also show how to correctly model and specify AgentSpeak agents and multi-agent systems with SLPN’s (Theorem 2). Both theorems allow us to solve the task of model checking AgentSpeak multi-agent systems by computing answer sets of the obtained logic program with any ASP system.     

Validation of reported events from a vertical chute marine evacuation study

Background

The use of vertical chute marine evacuation systems (MES) is now well established on board marine passenger vessels; this system has yet to be deployed in an emergency situation, however, it has been associated with a fatality and several major injuries during training. Brunel University's Ethics Committee endorsed an initial retrospective cross sectional study (Harwood and Farrow, 2008) and the present quantitative observational study. Harwood and Farrow (2008) found that the physical, physiological and psychological characteristics of potential evacuees increased the likelihood of injury and adversely affected the reliability of the system.

Purpose

The validation of factors associated with the adverse outcomes recorded by Harwood and Farrow (2008) during vertical chute MES training, and to assess the hypothesis that evacuee's clothing material will affect the efficiency of the system.

Design

Observational data in a marine training establishment providing a triangulation measurement process of evidence from the retrospective study (Harwood and Farrow, 2008). Subjects were three hundred and seventy five representative participants on training courses for evacuation from a ship into inflated life rafts. The main outcome measures were stopping during descent and exiting the chute in an undesirable position.

Results

6.1% stopped momentarily during descent; 20.3% exited the chute in an undesirable position; on entering the raft 7.7% flipped over and 9.1% had their legs tucked up under their bodies. Independent variables including evacuees' clothing material were statistically significantly associated with adverse outcomes. Participants stopping during descent had an RR of 3.03 (95% CI 1.38, 6.64) for exiting the chute in an undesirable position.

Conclusions

This quantitative observational study broadly supported the results obtained from the retrospective cross sectional study (Harwood and Farrow, 2008). Stopping during descent and evacuee clothing increased the likelihood of undesirable outcomes and impacted on the efficiency of the system.     

Symbolic Supervisory Control of Infinite Transition Systems Under Partial Observation Using Abstract Interpretation

We propose algorithms for the synthesis of state-feedback controllers with partial observation of infinite state discrete event systems modelled by Symbolic Transition Systems. We provide models of safe memoryless controllers both for potentially deadlocking and deadlock free controlled systems. The termination of the algorithms solving these problems is ensured using abstract interpretation techniques which provide an overapproximation of the transitions to disable. We then extend our algorithms to controllers with memory and to online controllers. We also propose improvements in the synthesis of controllers in the finite case which, to our knowledge, provide more permissive solutions than what was previously proposed in the literature. Our tool SMACS gives an empirical validation of our methods by showing their feasibility, usability and efficiency.     

Multicomponent Physical Vapor Deposited Films with Homogeneous Molecular Material Distribution Featuring Improved Resist Sensitivity

Each film preparation technique affects the physical properties of the resulting coating and thus defines its applicability in modern device construction. In this context solvent based spin coated and solvent‐free physical vapor deposited molecular glass photoresist films are systematically investigated for their dissolution behavior, sensitivity, and overall lithographic performance. These investigations demonstrate that the solvent‐free physical vapor deposition leads to a marked increase in sensitivity. This could be explained by the individual molecule by molecule deposition step producing a more homogeneous distribution of the multicomponent resist system, especially the photoacid generator. In addition, this assumption is supported by former published simulations focusing on aggregate formation within thin films. This work demonstrates that the lithographic sensitivity of multicomponent resist system is an intrinsic parameter to investigate molecular material distribution and indicates that the applied film preparation technique is crucial for the corresponding performance and applicability.     

Droplet formation by squeezing in a microfluidic cross-junction

In microfluidics, flow focusing is widely used to produce water-in-oil droplets in microchannels at high frequency. We here report an experimental study of droplet formation in a microfluidic cross-junction with a minimum number of geometrical parameters. We mostly focus on the squeezing regime, which is composed of two distinct steps: filling and pinching. The duration of each step (and corresponding volumes of each liquid phase) is analyzed. They vary according to both water and oil flow rates. These variations provide several insights about the fluid flows in both phases. We propose several scaling laws to relate the droplet volume and frequency to the flow rate of both phases. We also discuss the influence of surfactant and channel compliance on droplet formation.