Editorial

Environmental and social impact assessment are default elements of transport policypreparation and transport project appraisal in many OECD countries. In the recent pasthowever, it has been realised that such an approach does not suffice. Instead of representingpossible limiting factors, the aims and principles of sustainable development are to beregarded as the very point of departure for formulating transport policies, as is for exampleformulated in the European Commission White Paper on Transport (COM, 2001). This hasconsequences not only for policy formulation, but also for theresearch that is used to buildthe evidence about the actual and potential impacts of transport systems

The adequate integration of sustainability into transport policy

In this paper we discuss to what extent transport policy fails to integrate five types of external effects, and what kind of research needs follow from the objective to make transport sustainable. The discussion is a synthesis of the findings collected and synthesized in the framework of Focus Group 4 of the STELLA project. The assignment of Focus Group 4 was to draw up a set of recommendations for future transport policy-oriented research dealing with external effects, on the basis of a series of specialist workshops. Five different kinds of so-called external effects of transport were identified beforehand, being environment, safety and security, public health, land use and congestion. Safety and security as well as congestion are external effects in the sense that they are not ‘internalised’ in the price of the transport service, but they do affect predominantly others within the transport system. This means that with some delay the transport market still reacts to changes in the intensity of these effects, albeit biased or insufficient. The public goods character of both externalities however implies that public intervention is needed to attain better performance of these external effects, partly via internalisation of the external effects and partly via planning (i.e. by evaluating the trade-offs ex ante). The other external effects, however, are not only insufficiently internalised in the transport price, but they are also predominantly affecting parties outside the transport system. Consequently, changes in the intensity of these effects do not feed back directly into the transport market. In that case public intervention has even a more complicated task, since it takes more time and is more complicated to learn what are actually the right balances for the trade-offs between adequate access and, in turn, sustainability, spatial quality, and public health

Translating expert system rules into Ada code with validation and verification

The purpose of this ongoing research and development program is to develop software tools which enable the rapid development, upgrading, and maintenance of embedded real-time artificial intelligence systems. The goals of this phase of the research were to investigate the feasibility of developing software tools which automatically translate expert system rules into Ada code and develop methods for performing validation and verification testing of the resultant expert system. A prototype system was demonstrated which automatically translated rules from an Air Force expert system was demonstrated which detected errors in the execution of the resultant system. The method and prototype tools for converting AI representations into Ada code by converting the rules into Ada code modules and then linking them with an Activation Framework based run-time environment to form an executable load module are discussed. This method is based upon the use of Evidence Flow Graphs which are a data flow representation for intelligent systems. The development of prototype test generation and evaluation software which was used to test the resultant code is discussed. This testing was performed automatically using Monte-Carlo techniques based upon a constraint based description of the required performance for the system

Localization of Microscale Devices In Vivo using Addressable Transmitters Operated as Magnetic Spins

The function of miniature wireless medical devices, such as capsule endoscopes, biosensors and drug-delivery systems, depends critically on their location inside the body. However, existing electromagnetic, acoustic and imaging-based methods for localizing and communicating with such devices suffer from limitations arising from physical tissue properties or from the performance of the imaging modality. Here, we embody the principles of nuclear magnetic resonance in a silicon integrated-circuit approach for microscale device localization. Analogous to the behaviour of nuclear spins, the engineered miniaturized radio frequency transmitters encode their location in space by shifting their output frequency in proportion to the local magnetic field; applied field gradients thus allow each device to be located precisely from its signal’s frequency. The devices are integrated in circuits smaller than 0.7 mm3 and manufactured through a standard complementary-metal-oxide-semiconductor process, and are capable of sub-millimetre localization in vitro and in vivo. The technology is inherently robust to tissue properties, scalable to multiple devices, and suitable for the development of microscale devices to monitor and treat disease

Acoustically Targeted Chemogenetics for Noninvasive Control of Neural Circuits

Neurological and psychiatric disorders are often characterized by dysfunctional neural circuits in specific regions of the brain. Existing treatment strategies, including the use of drugs and implantable brain stimulators, aim to modulate the activity of these circuits. However, they are not cell-type-specific, lack spatial targeting or require invasive procedures. Here, we report a cell-type-specific and non-invasive approach based on acoustically targeted chemogenetics that enables the modulation of neural circuits with spatiotemporal specificity. The approach uses ultrasound waves to transiently open the blood–brain barrier and transduce neurons at specific locations in the brain with virally encoded engineered G-protein-coupled receptors. The engineered neurons subsequently respond to systemically administered designer compounds to activate or inhibit their activity. In a mouse model of memory formation, the approach can modify and subsequently activate or inhibit excitatory neurons within the hippocampus, with selective control over individual brain regions. This technology overcomes some of the key limitations associated with conventional brain therapies

Higher Derivative Operators as Counterterms in Orbifold Compactifications

In the context of 5D N=1 supersymmetric models compactified on S_1/Z_2 or S_1/(Z_2 x Z_2') orbifolds and with brane-localised superpotential, higher derivative operators are generated radiatively as one-loop counterterms to the mass of the (brane or zero mode of the bulk) scalar field. It is shown that the presence of such operators which are brane-localised is not related to the mechanism of supersymmetry breaking considered (F-term, discrete or continuous Scherk-Schwarz breaking) and initial supersymmetry does not protect against the dynamical generation of such operators. Since in many realistic models the scalar field is commonly regarded as the Higgs field, and the higher derivative operators seem a generic presence in orbifold compactifications, we stress the importance of these operators for solving the hierarchy problem.Comment: Contribution to the Conference "Supersymmetry 2005", Durham; 13 pages, LaTe

Biomolecular Ultrasound Imaging of Phagolysosomal Function

Phagocytic clearance and lysosomal processing of pathogens and debris are essential functions of the innate immune system. However, the assessment of these functions in vivo is challenging because most nanoscale contrast agents compatible with noninvasive imaging techniques are made from nonbiodegradable synthetic materials that do not undergo regular lysosomal degradation. To overcome this challenge, we describe the use of an all-protein contrast agent to directly visualize and quantify phagocytic and lysosomal activities in vivo by ultrasound imaging. This contrast agent is based on gas vesicles (GVs), a class of air-filled protein nanostructures naturally expressed by buoyant microbes. Using a combination of ultrasound imaging, pharmacology, immunohistology, and live-cell optical microscopy, we show that after intravenous injection, GVs are cleared from circulation by liver-resident macrophages. Once internalized, the GVs undergo lysosomal degradation, resulting in the elimination of their ultrasound contrast. By noninvasively monitoring the temporal dynamics of GV-generated ultrasound signal in circulation and in the liver and fitting them with a pharmacokinetic model, we can quantify the rates of phagocytosis and lysosomal degradation in living animals. We demonstrate the utility of this method by showing how these rates are perturbed in two models of liver dysfunction: phagocyte deficiency and nonalcoholic fatty liver disease. The combination of proteolytically degradable nanoscale contrast agents and quantitative ultrasound imaging thus enables noninvasive functional imaging of cellular degradative processes