Call-by-Value {lambda}-calculus and LJQ

LJQ is a focused sequent calculus for intuitionistic logic,with a simple restriction on the first premiss of the usualleft introduction rule for implication. In a previous paperwe discussed its history (going back to about 1950, or beyond)and presented its basic theory and some applications; here wediscuss in detail its relation to call-by-value reduction inlambda calculus, establishing a connection between LJQ and theCBV calculus _C of Moggi. In particular, we present an equationalcorrespondence between these two calculi forming a bijectionbetween the two sets of normal terms, and allowing reductionsin each to be simulated by reductions in the other.     

Protocol considerations for a prefix-caching proxy for multimedia streams

The increasing popularity of multimedia streaming applications introduces new challenges in content distribution. Web-initiated multimedia streams typically experience high start-up delay, due to large protocol overheads and the poor delay, throughput, and loss properties of the Internet. Internet service providers can improve performance by caching the initial segment (the prefix) of popular streams at proxies near the requesting clients. The proxy can initiate transmission to the client while simultaneously requesting the remainder of the stream from the server. This paper analyzes the challenges of realizing a prefix-caching service in the context of the IETF's Real-Time Streaming Protocol (RTSP), a multimedia streaming protocol that derives from HTTP. We describe how to exploit existing RTSP features, such as the Range header, and how to avoid several round-trip delays by caching protocol information at the proxy. Based on our experiences, we propose extensions to RTSP that would ease the development of new multimedia proxy services. In addition, we discuss how caching the partial contents of multimedia streams introduces new challenges in cache coherency and feedback control. Then, we briefly present our preliminary implementation of prefix caching on a Linux-based PC, and describe how the proxy interoperates with the RealNetworks server and client.     

Mobile agents and intellectual property protection

Technical enforcemment of intellectual property (IP) rights often conflicts with the ability to use the IP. This is especially true when the IP is data, which may eaisly be copied while it is being accessed. As electronic commerce of data becomes more widespread, traditional approaches will prove increasingly problematic. In this paper, we show that the mobile agent architecture is an ideal solution to this dilemma: by providing full access to the data but charging for the transmission of results back to the user-reslts-based billing-we resulve the access versus protection conflict. We define new requirements for agent frameworks to implement results-based billing: data-aware accounting and data-tight sandboxing, which, along with the common requirements such as authentication, authorisation, agen self-monitoring, and efficiency, provide the mechanisms by which database owners can effectively grant users access to their intellectual property.     

Comparative study between computational and experimental results for binary rarefied gas flows through long microchannels

A comparative study between computational and experimental results for pressure-driven binary gas flows through long microchannels is performed. The theoretical formulation is based on the McCormack kinetic model and the computational results are valid in the whole range of the Knudsen number. Diffusion effects are taken into consideration. The experimental work is based on the Constant Volume Method, and the results are in the slip and transition regime. Using both approaches, the molar flow rates of the He–Ar gas mixture flowing through a rectangular microchannel are estimated for a wide range of pressure drops between the upstream and downstream reservoirs and several mixture concentrations varying from pure He to pure Ar. In all cases, a very good agreement is found, within the margins of the introduced modeling and measurement uncertainties. In addition, computational results for the pressure and concentration distributions along the channel are provided. As far as the authors are aware of, this is the first detailed and complete comparative study between theory and experiment for gaseous flows through long microchannels in the case of binary mixtures.     

Effects of host plant development and genetic determinants on the long-distance movement of cauliflower mosaic virus in Arabidopsis

During systemic infections, viruses move long distances through the plant vascular system. The long-distance movement of cauliflower mosaic virus (CaMV) in Arabidopsis has been examined using a whole plant in situ hybridization technique called plant skeleton hybridization. CaMV moves long distance through the phloem largely following the flow of photoassimilates from source to sink leaves. During the course of plant development, sink-source relationships change and the region of the plant that CaMV can invade is progressively reduced. In Arabidopsis, we have found that conditions that influence the rate of plant development dramatically impact the long-distance movement of CaMV, because under normal conditions the rate of plant development is closely matched to the kinetics of virus movement. Ecotypes and mutants of Arabidopsis that flower early show a form of resistance to systemic CaMV infection, which we call "developmental resistance." Developmental resistance results from the fact that the rosette leaves mature early in the life of an early flowering plant and become inaccessible to virus. On the other hand, if the development of early flowering plants is retarded by suboptimal growth conditions, inoculated plants appear more susceptible to the virus and systemic infections become more widespread. We have found that other Arabidopsis ecotypes, such as Enkheim-2 (En-2), show another form of resistance to virus movement that is not based on developmental or growth conditions. The virus resistance in ecotype En-2 is largely conditioned by a dominant trait at a single locus.     

A parallel algorithm for constrained two-staged two-dimensional cutting problems

In this paper, we solve the two-staged two-dimensional cutting problem using a parallel algorithm. The proposed approach combines two main features: beam search (BS) and strip generation solution procedures (SGSP). BS employs a truncated tree-search, where a selected subset of generated nodes are retuned for further search. SGSP, a constructive procedure, combines a (sub)set of strips for providing both partial lower and complementary upper bounds. The algorithm explores in parallel a subset of selected nodes following the master-slave paradigm. The master processor serves to guide the search-resolution and each slave processor develops its proper way, trying a global convergence. The aim of such an approach is to show how the parallelism is able to efficiently solve large-scale instances, by providing new solutions within a consistently reduced runtime. Extensive computational testing on instances, taken from the literature, shows the effectiveness of the proposed approach.     

Disease-Induced Modulation of Drug Transporters at the Blood–Brain Barrier Level

The blood–brain barrier (BBB) is a highly selective and restrictive semipermeable network of cells and blood vessel constituents. All components of the neurovascular unit give to the BBB its crucial and protective function, i.e., to regulate homeostasis in the central nervous system (CNS) by removing substances from the endothelial compartment and supplying the brain with nutrients and other endogenous compounds. Many transporters have been identified that play a role in maintaining BBB integrity and homeostasis. As such, the restrictive nature of the BBB provides an obstacle for drug delivery to the CNS. Nevertheless, according to their physicochemical or pharmacological properties, drugs may reach the CNS by passive diffusion or be subjected to putative influx and/or efflux through BBB membrane transporters, allowing or limiting their distribution to the CNS. Drug transporters functionally expressed on various compartments of the BBB involve numerous proteins from either the ATP-binding cassette (ABC) or the solute carrier (SLC) superfamilies. Pathophysiological stressors, age, and age-associated disorders may alter the expression level and functionality of transporter protein elements that modulate drug distribution and accumulation into the brain, namely, drug efficacy and toxicity. This review focuses and sheds light on the influence of inflammatory conditions and diseases such as Alzheimer’s disease, epilepsy, and stroke on the expression and functionality of the BBB drug transporters, the consequential modulation of drug distribution to the brain, and their impact on drug efficacy and toxicity.     

Chronic Inflammatory Status Observed in Patients with Type 2 Diabetes Induces Modulation of Cytochrome P450 Expression and Activity

Diabetes mellitus is a metabolic disease that causes a hyperglycemic status which leads, over time, to serious damage to the heart, blood vessels, eyes, kidneys and nerves. The most frequent form of diabetes is type 2 diabetes mellitus (T2DM) which is often part of a metabolic syndrome (hyperglycaemia, hypertension, hypercholesterolemia, abdominal obesity) that usually requires the use of several medications from different drug classes to bring each of these conditions under control. T2DM is associated with an increase in inflammatory markers such as interleukin-6 (IL-6) and the tumor necrosis factor alpha (TNF-α). Higher levels of IL-6 and TNF-α are associated with a downregulation of several drug metabolizing enzymes, especially the cytochrome P450 (P450) isoforms CYP3As and CYP2C19. A decrease in these P450 isoenzymes may lead to unexpected rise in plasma levels of substrates of these enzymes. It could also give rise to a mismatch between the genotypes determined for these enzymes, the predicted phenotypes based on these genotypes and the phenotypes observed clinically. This phenomenon is described as phenoconversion. Phenoconversion typically results from either a disease (such as T2DM) or concomitant administration of medications inducing or inhibiting (including competitive or non-competitive inhibition) a P450 isoenzyme used by other substrates for their elimination. Phenoconversion could have a significant impact on drug effects and genotypic-focused clinical outcomes. As the aging population is exposed to polypharmacy along with inflammatory comorbidities, consideration of phenoconversion related to drug metabolizing enzymes is of importance when applying pharmacogenomic results and establishing personalized and more precise drug regimens.     

Tracking Fronts in One and Two-phase Incompressible Flows Using an Adaptive Mesh Refinement Approach

Numerical computation is an essential tool for describing multi-phase and multi-scale flows accurately. One possibility consists in using very fine monogrids to obtain accurate solutions. However, this approach is very costly in time and memory size. As an alternative, an Adaptive Mesh Refinement method (AMR) has been developed in order to follow either interfaces in two-phase flows or concentration of a pollutant in one-phase flows. This method has also been optimized to reduce time and memory costs. Several 2D cases have been studied to validate and show the efficiency of the method.