Independent AND-parallel implementation of narrowing

We present a parallel graph narrowing machine, which is used to implement a functional logic language on a shared memory multiprocessor. It is an extensión of an abstract machine for a purely functional language. The result is a programmed graph reduction machine which integrates the mechanisms of unification, backtracking, and independent and-parallelism. In the machine, the subexpressions of an expression can run in parallel. In the case of backtracking, the structure of an expression is used to avoid the reevaluation of subexpressions as far as possible. Deterministic computations are detected. Their results are maintained and need not be reevaluated after backtracking.

Dimensional synthesis of a spherical parallel manipulator based on the evaluation of global performance indexes

In this work, the dimensional synthesis of a spherical Parallel Manipulator (PM) with a -1S kinematic chain is presented. The goal of the synthesis is to find a set of parameters that defines the PM with the best performance in terms of workspace capabilities, dexterity and isotropy. The PM is parametrized in terms of a reference element, and a non-directed search of these parameters is carried out. First, the inverse kinematics and instantaneous kinematics of the mechanism are presented. The latter is found using the screw theory formulation. An algorithm that explores a bounded set of parameters and determines the corresponding value of global indexes is presented. The concepts of a novel global performance index and a compound index are introduced. Simulation results are shown and discussed. The best PMs found in terms of each performance index evaluated are locally analyzed in terms of its workspace and local dexterity. The relationship between the performance of the PM and its parameters is discussed, and a prototype with the best performance in terms of the compound index is presented and analyzed.

Intraply fracture of fiber-reinforced composites: microscopic mechanisms and modeling

The fracture behavior parallel to the fibers of an E-glass/epoxy unidirectional laminate was studied by means of three-point tests on notched beams. Selected tests were carried out within a scanning electron microscope to ascertain the damage and fracture micromechanisms upon loading. The mechanical behavior of the notched beam was simulated within the framework of the embedded cell model, in which the actual composite microstructure was resolved in front of the notch tip. In addition, matrix and interface properties were independently measured in situ using a nanoindentor. The numerical simulations very accurately predicted the macroscopic response of the composite as well as the damage development and crack growth in front of the notch tip, demonstrating the ability of the embedded cell approach to simulate the fracture behavior of heterogeneous materials. Finally, this methodology was exploited to ascertain the influence of matrix and interface properties on the intraply toughness.

Application of the agency theory for the analysis of performance-based mechanisms in road management

El WCTR es un congreso de reconocido prestigio internacional en el ámbito de la investigación del transporte, y aunque las actas publicadas están en formato digital y sin ISSN ni ISBN, lo consideramos lo suficientemente importante como para que se considere en los indicadores. This paper develops a model based on agency theory to analyze road management systems (under the different contract forms available today) that employ a mechanism of performance indicators to establish the payment of the agent. The base assumption is that of asymmetric information between the principal (Public Authorities) and the agent (contractor) and the risk aversion of this latter. It is assumed that the principal may only measure the agent?s performance indirectly and by means of certain performance indicators that may be verified by the authorities. In this model there is presumed to be a relation between the efforts made by the agent and the performance level measured by the corresponding indicators, though it is also considered that there may be dispersion between both variables that gives rise to a certain degree of randomness in the contract. An analysis of the optimal contract has been made on the basis of this model and in accordance with a series of parameters that characterize the economic environment and the particular conditions of road infrastructure. As a result of the analysis made, it is considered that an optimal contract should generally combine a fixed component and a payment in accordance with the performance level obtained. The higher the risk aversion of the agent and the greater the marginal cost of public funds, the lower the impact of this performance-based payment. By way of conclusion, the system of performance indicators should be as broad as possible but should not overweight those indicators that encompass greater randomness in their results.

Cochlear mechanisms from a phylogenetic viewpoint

The hearing organ of the inner ear was the last of the paired sense organs of amniotes to undergo formative evolution. As a mechanical sensory organ, the inner-ear hearing organ's function depends highly on its physical structure. Comparative studies suggest that the hearing organ of the earliest amniote vertebrates was small and simple, but possessed hair cells with a cochlear amplifier mechanism, electrical frequency tuning, and incipient micromechanical tuning. The separation of the different groups of amniotes from the stem reptiles occurred relatively early, with the ancestors of the mammals branching off first, approximately 320 million years ago. The evolution of the hearing organ in the three major lines of the descendents of the stem reptiles (e.g., mammals, birds-crocodiles, and lizards-snakes) thus occurred independently over long periods of time. Dramatic and parallel improvements in the middle ear initiated papillar elongation in all lineages, accompanied by increased numbers of sensory cells with enhanced micromechanical tuning and group-specific hair-cell specializations that resulted in unique morphological configurations. This review aims not only to compare structure and function across classification boundaries (the comparative approach), but also to assess how and to what extent fundamental mechanisms were influenced by selection pressures in times past (the phylogenetic viewpoint).

Economic cycles, asymmetric crises and tourism competitiveness: emerging versus mature destinations

This paper considers the influence of business cycles and economic crises on tourism destinations competitiveness. This competitiveness is measured by its share in world tourism. Analysing a period of forty years, the differential permanent or temporary effects that economic crises has on competitiveness of mature and emerging destinations are observed. Furthermore, it identifies the economic transmission mechanisms operating within this context, analysing them using the framework of the most relevant explanatory models of tourism destination competitiveness. The preliminary results obtained suggest that the effects of these shocks on competitiveness are not neutral. In mature destinations the negative effects are more persistent in highly intensive crises. In emerging destinations with a growing natural trend on tourism demand, the effects of the economic crises are softer and limited, reinforcing the process of convergence between destinations. This effect works through two basic transmission mechanisms: the reduction of internal and external tourism demand and the decrease on investment.

A real-time asymmetric multiprocessor-reconfigurable system-on-chip architecture

We propose an asymmetric multi-processor SoC architecture, featuring a master CPU running uClinux, and multiple loosely-coupled slave CPUs running real-time threads assigned by the master CPU. Real-time SoC architectures often demand a compromise between a generic platform for different applications, and application-specific customizations to achieve performance requirements. Our proposed architecture offers a generic platform running a conventional embedded operating system providing a traditional software-oriented development approach, while multiple slave CPUs act as a dedicated independent real-time threads execution unit running in parallel of master CPU to achieve performance requirements. In this paper, the architecture is described, including the application / threading development environment. The performance of the architecture with several standard benchmark routines is also analysed.

Parallel geostatistics for sparse and dense datasets

Very large spatially-referenced datasets, for example, those derived from satellite-based sensors which sample across the globe or large monitoring networks of individual sensors, are becoming increasingly common and more widely available for use in environmental decision making. In large or dense sensor networks, huge quantities of data can be collected over small time periods. In many applications the generation of maps, or predictions at specific locations, from the data in (near) real-time is crucial. Geostatistical operations such as interpolation are vital in this map-generation process and in emergency situations, the resulting predictions need to be available almost instantly, so that decision makers can make informed decisions and define risk and evacuation zones. It is also helpful when analysing data in less time critical applications, for example when interacting directly with the data for exploratory analysis, that the algorithms are responsive within a reasonable time frame. Performing geostatistical analysis on such large spatial datasets can present a number of problems, particularly in the case where maximum likelihood. Although the storage requirements only scale linearly with the number of observations in the dataset, the computational complexity in terms of memory and speed, scale quadratically and cubically respectively. Most modern commodity hardware has at least 2 processor cores if not more. Other mechanisms for allowing parallel computation such as Grid based systems are also becoming increasingly commonly available. However, currently there seems to be little interest in exploiting this extra processing power within the context of geostatistics. In this paper we review the existing parallel approaches for geostatistics. By recognising that diffeerent natural parallelisms exist and can be exploited depending on whether the dataset is sparsely or densely sampled with respect to the range of variation, we introduce two contrasting novel implementations of parallel algorithms based on approximating the data likelihood extending the methods of Vecchia [1988] and Tresp [2000]. Using parallel maximum likelihood variogram estimation and parallel prediction algorithms we show that computational time can be significantly reduced. We demonstrate this with both sparsely sampled data and densely sampled data on a variety of architectures ranging from the common dual core processor, found in many modern desktop computers, to large multi-node super computers. To highlight the strengths and weaknesses of the diffeerent methods we employ synthetic data sets and go on to show how the methods allow maximum likelihood based inference on the exhaustive Walker Lake data set.

Egg quality and fecundity in rainbow trout: the determining factors and mechanisms of control

This thesis considers the factors involved in the determination of egg quality and fecundity in farmed stocks of rainbow trout ( Salmo gairdneri R) • Measurements of egg quality, ie. percentage survivals of eggs and fry, from the production batches of eggs of seven fish farms, showed mean survivals of 70% to eying but levels of only 35% to 4.5g fry (approx. 130 days post-fertilisation). Under optimum conditions survivals may reach 85% suggesting that husbandry methods exert significant influences on egg quality. Chemical analyses of the protein, fat, vitellogenin, ash, amino acids, free fatty acid and mineral levels of eggs of varying quality and from parents of different strains showed compositional differences even between individuals of the same stock. However, none of these differences were correlated with egg quality. Egg size showed similar variations but, again under hatchery conditions there was no correlation with differences in egg quality. The only factor which has been shown to exert a significant influence on egg quality is the time of stripping after ovulation. At 1 0°C eggs should be removed from gravid females within ten days of ovulation to achieve optimum egg and fry survival. Studies of egg production from approximately 10,000 broodstock revealed that total fecundity and egg size increased and relative fecundity decreased with increasing fish size. In general, most fish appeared to produce a constant volume of eggs. This is consistent with a hypothesis that egg size can only be increased by parallel reductions in fecundity. Feeding broodstock at half-ration (0.35% body weight day- 1 ) did not affect egg quality but reduced total fecundity and egg size and increased relative fecundity when compared with eggs produced by fish on full-ration. Comparisons of regressions of total fecundity against fish weight for three strains using ANOCO revealed that one strain was significantly more fecund than two other strains considered. Trout of the same strain maintained on different farms behaved similarly suggesting there was some reproducibility of strain characteristics.

An investigation into the synaptic conditions and celluar mechanisms underlying cerebellar synaptic plasticity

The direction of synaptic plasticity at the connection between parallel fibres (PFs) and Purkinje cells can be modified by PF stimulation alone. Strong activation (Hartell, 1996) or high frequency stimulation (Schreurs and Alkon, 1993) of PFs induced a long-term depression (LTD) of PF-mediated excitatory postsynaptic currents. Brief raised frequency molecular layer stimulation produced a cAMP-dependent long-temi potentiation (LTP) of field potential (FP) responses (Salin et al., 1998). Thin slices of cerebellar vermis were prepared from 14-21 day old male Wistar rats decapitated under Halothane anaesthesia. FP's were recorded from the Purkinje cell layer in response to alternate 0.2Hz activation of stimulating electrodes placed in the molecular layer. In the presence of picrotoxin, FPs displayed two tetrodotoxin-sensitive, negative-going components termed N1 and N2. EPs were graded responses with paired pulse facilitation and were selectively blocked by 101AM 6-cyano-7-nitroquinoxaline-2,3-dicne (CNQX) an antagonist at iy,-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-type ionotropic glutamate receptors (AMPAR) suggesting that they were primarily PE-mediated. The effects of raised stimulus intensity (RS) and/or increased frequency (IF) activation of the molecular layer on FP responses were examined. In sagittai and transverse slices combined RS and IF molecular layer activation induced a LTD of the N2 component of FP responses. RSIF stimulation produced fewer incidences of LTD in sagittal slices when an inhibitor of nitric oxide synthase (NOS), guanylate cyclase (GC), protein kinase G (PKG) or the GABAB receptor antagonist CGP62349 was included into the perfusion medium. Application of a nitric oxide (NO) donor, a cyclic guanosine monophosphate (cGMP) analogue or a phosphodiesterase (PDE) type V inhibitor to prevent cGMP breakdown paired with IF stimulation produced an acute depression, Raised frequency (RF) molecular layer stimulation produced a slowly emerging LTD of N2 in sagittal slices that was largely blocked in the presence of NOS, cGMP or PKG inhibitors. In transverse slices RE stimulation produced a LTP of the N2 component that was prevented by an inhibitor of protein kinase A or NOS. Inhibition of cGMP-signalling frequently revealed an underlying potentiation suggesting that cGMP activity might mask the effects of cAMP. In sagittal slices RE stimulation resulted in a potentiation of FPs when the cAMP-specific PDE type IV inhibitor rolipram was incorporated into the perfusion medium. In summary, raised levels of PE stimulation can alter the synaptic efficacy at PF-Purkinje cell synapses. The results provide support for a role of NO/cGMP/PKG signalling in the induction of LTD in the cerebellar cortex and suggest that activation of GABAa receptors might also be important. The level of cyclic nucleotide-specific PDE activities may be crucial in determining the level of cGMP and CAMP activity and hence the direction of synaptic plasticity.

On the mechanisms of cerebellar synaptic plasticity

Changes in the strength of signalling between neurones are thought to provide a cellular substrate for learning and memory. In the cerebellar cortex, raising the frequency and the strength of parallel fibre (PF) stimulation leads to a long-term depression (LTD) of the strength of signalling at the synapse between PFs and Purkinje cells (PCs), which spreads to distant synapses to the same cell via a nitric oxide (NO) dependent mechanism. At the same synapse, but under conditions of reduced post-synaptic calcium activity, raised frequency stimulation (RFS) of PFs triggers a long-term potentiation of synaptic transmission. The aims of the work described in this thesis were to investigate the conditions necessary for LTD and LTP at this synapse following RFS and to identify the origins and second messenger cascades involved in the induction and spread of LTP and LTD. In thin, parasagittal cerebellar slices whole cell patch clamp recordings were made from PCs and the effects of RFS of one of two, independent PF inputs to the same PC were examined under a range of experimental conditions. Under conditions designed to reduce post-synaptic calcium activity, RFS to a single PF input led to LTP and a decreases in paired pulse facilitation (PPF) in both pathways. This heterosynaptic potentiation was prevented by inhibition of protein kinase A (PKA) or by inhibition of NO synthase with either 7-nitroindazole (7-NI) or NG Nitro-L-argenine methyl ester. Inhibition of guanylate cyclase (GC) or protein kinase G (PKG) had no effect. A similar potentiation was observed upon application of the adenylyl cyclase (AC) activator forskolin or the NO donor spermine NONOate. Both of these treatments also resulted in an increase in the frequency of mEPSCs, which provides further evidence for a presynaptic origin of LTP. Forskolin induced potentiation and the increase in mEPSC frequency were blocked by 7-NI. The styryl dye FM1-43, a fluorescent reporter of endo- and exocytosis, was also used to further examine the possible pre-synaptic origins of LTP. RFS or forskolin application enhanced FM1-43 de-staining and NOS inhibitors blocked this effect. Application of NONOate also enhanced FM1-43 de-staining. When post-synaptic calcium activity was less strictly buffered, RFS to a single PF input led to a transient potentiation that was succeeded by LTD in both pathways. This LTD, which resembled previously described forms, was prevented by inhibition of the NO/cGMP/PKG cascade. Modification of the AC/cAMP/PKA cascade had no effect. In summary, the direction of synaptic plasticity at the PF-PC synapse in response to RFS depends largely on the level of post-synaptic calcium activity. LTP and LTD were non-input specific and both forms of plasticity were dependent on NOS activity. Induction of LTP was mediated by a presynaptic mechanism and depended on NO and cAMP production. LTD on the other hand was a post-synaptic process and required activity of the NO/cGMP/PKG signalling cascade.

Cortical mechanisms of attention in time:neural correlates of the Lag-1-sparing phenomenon

If humans monitor streams of rapidly presented (approximately 100-ms intervals) visual stimuli, which are typically specific single letters of the alphabet, for two targets (T1 and T2), they often miss T2 if it follows T1 within an interval of 200-500 ms. If T2 follows T1 directly (within 100 ms; described as occurring at 'Lag 1'), however, performance is often excellent: the so-called 'Lag-1 sparing' phenomenon. Lag-1 sparing might result from the integration of the two targets into the same 'event representation', which fits with the observation that sparing is often accompanied by a loss of T1-T2 order information. Alternatively, this might point to competition between the two targets (implying a trade-off between performance on T1 and T2) and Lag-1 sparing might solely emerge from conditional data analysis (i.e. T2 performance given T1 correct). We investigated the neural correlates of Lag-1 sparing by carrying out magnetoencephalography (MEG) recordings during an attentional blink (AB) task, by presenting two targets with a temporal lag of either 1 or 2 and, in the case of Lag 2, with a nontarget or a blank intervening between T1 and T2. In contrast to Lag 2, where two distinct neural responses were observed, at Lag 1 the two targets produced one common neural response in the left temporo-parieto-frontal (TPF) area but not in the right TPF or prefrontal areas. We discuss the implications of this result with respect to competition and integration hypotheses, and with respect to the different functional roles of the cortical areas considered. We suggest that more than one target can be identified in parallel in left TPF, at least in the absence of intervening nontarget information (i.e. masks), yet identified targets are processed and consolidated as two separate events by other cortical areas (right TPF and PFC, respectively).

Mechanisms of Arsenic Detoxification and Resistance

Arsenic is a ubiquitous environmental toxic substance. As a consequence of continual exposure to arsenic, nearly every organism, from Escherichia coli to humans have evolved arsenic detoxification pathways. One of the pathways is extrusion of arsenic from inside the cells, thereby conferring resistance. The R773 arsRDABC operon in E. coli encodes an ArsAB efflux pump that confers resistance to arsenite. ArsA is the catalytic subunit of the pump, while ArsB forms the oxyanion conducting pathway. ArsD is an arsenite metallochaperone that binds arsenite and transfers it to ArsA. The interaction of ArsA and ArsD allows for resistance to As(III) at environmental concentrations. The interaction between ArsA ATPase and ArsD metallochaperone was examined. A quadruple mutant in the arsD gene encoding a K2A/K37A/K62A/K104A ArsD is unable to interact with ArsA. An error-prone mutagenesis approach was used to generate random mutations in the arsA gene that restored interaction with the quadruple arsD mutant in yeast two-hybrid assays. Three such mutants encoding Q56R, F120I and D137V ArsA were able to restore interaction with the quadruple ArsD mutant. Structural models generated by in silico docking suggest that an electrostatic interface favors reversible interaction between ArsA and ArsD. Mutations in ArsA that propagate changes in hydrogen bonding and salt bridges to the ArsA-ArsD interface also affect their interactions. The second objective was to examine the mechanism of arsenite resistance through methylation and subsequent volatilization. Microbial ArsM (As(III) S-adenosylmethyltransferase) catalyzes the formation of trimethylarsine as the volatile end product. The net result is loss of arsenic from cells. The gene for CrArsM from the eukaryotic green alga Chlamydomonas reinhardtii was chemically synthesized and expressed in E. coli. The purified protein catalyzed the methylation of arsenite into methyl-, dimethyl- and trimethyl products. Synthetic purified CrArsM was crystallized in an unliganded form. Biochemical and biophysical studies conducted on CrArsM sheds new light on the pathways of biomethylation. While in microbes ArsM detoxifies arsenic, the human homolog, hAS3MT, converts inorganic arsenic into more toxic and carcinogenic forms. An understanding of the enzymatic mechanism of ArsM will be critical in deciphering its parallel roles in arsenic detoxification and carcinogenesis.

Design, development and control of a new generation high performance linear actuator for parallel robots and other applications

The main focus of this research is to design and develop a high performance linear actuator based on a four bar mechanism. The present work includes the detailed analysis (kinematics and dynamics), design, implementation and experimental validation of the newly designed actuator. High performance is characterized by the acceleration of the actuator end effector. The principle of the newly designed actuator is to network the four bar rhombus configuration (where some bars are extended to form an X shape) to attain high acceleration. Firstly, a detailed kinematic analysis of the actuator is presented and kinematic performance is evaluated through MATLAB simulations. A dynamic equation of the actuator is achieved by using the Lagrangian dynamic formulation. A SIMULINK control model of the actuator is developed using the dynamic equation. In addition, Bond Graph methodology is presented for the dynamic simulation. The Bond Graph model comprises individual component modeling of the actuator along with control. Required torque was simulated using the Bond Graph model. Results indicate that, high acceleration (around 20g) can be achieved with modest (3 N-m or less) torque input. A practical prototype of the actuator is designed using SOLIDWORKS and then produced to verify the proof of concept. The design goal was to achieve the peak acceleration of more than 10g at the middle point of the travel length, when the end effector travels the stroke length (around 1 m). The actuator is primarily designed to operate in standalone condition and later to use it in the 3RPR parallel robot. A DC motor is used to operate the actuator. A quadrature encoder is attached with the DC motor to control the end effector. The associated control scheme of the actuator is analyzed and integrated with the physical prototype. From standalone experimentation of the actuator, around 17g acceleration was achieved by the end effector (stroke length was 0.2m to 0.78m). Results indicate that the developed dynamic model results are in good agreement. Finally, a Design of Experiment (DOE) based statistical approach is also introduced to identify the parametric combination that yields the greatest performance. Data are collected by using the Bond Graph model. This approach is helpful in designing the actuator without much complexity.

A long non-coding RNA targets microRNA miR-34a to regulate colon cancer stem cell asymmetric division.

The roles of long non-coding RNAs (lncRNAs) in regulating cancer and stem cells are being increasingly appreciated. Its diverse mechanisms provide the regulatory network with a bigger repertoire to increase complexity. Here we report a novel LncRNA, Lnc34a, that is enriched in colon cancer stem cells (CCSCs) and initiates asymmetric division by directly targeting the microRNA miR-34a to cause its spatial imbalance. Lnc34a recruits Dnmt3a via PHB2 and HDAC1 to methylate and deacetylate the miR-34a promoter simultaneously, hence epigenetically silencing miR-34a expression independent of its upstream regulator, p53. Lnc34a levels affect CCSC self-renewal and colorectal cancer (CRC) growth in xenograft models. Lnc34a is upregulated in late-stage CRCs, contributing to epigenetic miR-34a silencing and CRC proliferation. The fact that lncRNA targets microRNA highlights the regulatory complexity of non-coding RNAs (ncRNAs), which occupy the bulk of the genome.