Intermediate Path Research Articles

Environmental surveillance of norovirus in Argentina revealed distinct viral diversity patterns, seasonality and spatio-temporal diffusion processes

Norovirus (NoV) contamination was evaluated in five rivers of Argentina between 2005 and 2011. NoV was present in all sampled rivers, with distinct NoV patterns in waters impacted by different-sized communities. In rivers affected by medium-sized populations (Salta and Córdoba cities) only one or two genotypes were present, GII.4 being the main one, with winter seasonality. In contrast, in the much more heavily populated area of Buenos Aires city the prevalent GII.4 was accompanied by several additional genotypes (GII.4, GII.b, GII.2, GII.7, GII.17, GII.e and GII.g) and one ungenotyped GII NoV, with no clear seasonality.GII.4 2006b was the main variant detected (60.9%). Phylogeographic and phylodynamic analyses performed in region D of the VP1 gene showed a most recent common ancestor in 2002 and a substitution rate of 3.7×10−3 substitutions per site per year (HPD95%=2.3×10−3−5.2×10−3) for this variant still involving a significant population size with a slight decrease since 2008. The spatio-temporal diffusion analysis proposed Europe as an intermediate path between the American Continent and the rest of the World for NoV dissemination.Given the importance of NoV as a cause of epidemic gastroenteritis and the likelihood of its environmental transmission, the results of this work should increase public and institutional awareness of the health risk involved in sewage discharges into the environment. Environmental surveillance of enteric viruses could be a very useful tool not only to prevent waterborne outbreaks, but also to describe the epidemiology of the viruses. The detailed analysis of the viral genomes disposed into the environment contributed to the characterization of the dissemination, diversity and seasonality of NoV in its natural host population. In future studies, environmental surveillance and molecular analysis should be complemented with a quantitative viral risk assessment for estimating the disease burden from viruses in the environment.

Performance debugging of Esterel specifications

Synchronous languages like Esterel have been widely adopted for designing reactive systems in safety-critical domains such as avionics. Specifications written in Esterel are based on the underlying synchrony hypothesis, which needs to be validated when Esterel specifications get compiled to real implementations (such as C code). In this work, we present a model-driven and architecture-aware timing analysis framework for C code generated from Esterel and executed on general-purpose processors. By integrating model-level information into the traditional timing analysis, we can efficiently compute accurate time estimates via systematically eliminating a large number of infeasible paths in the generated code. Experimental results show that with our proposed intermediate representation level infeasible path analysis in the model compilation, we obtain up to 16.1 % tighter WCET estimates compared to the traditional assembly code level infeasible path detection with substantially less analysis time. Furthermore, by maintaining the traceability links between Esterel specifications and the generated C code, we are able to map the time-critical computations at the C-level back to the Esterel-level.

Electric field induced intermediate phase and polarization rotation path in alkaline niobate based piezoceramics close to the rhombohedral and tetragonal phase boundary

High resolution synchrotron x-ray and dielectric measurements on unpoled and poled (Na,K)(Nb,Sb)O3-LiTaO3-xBaZrO3 lead-free ceramics close to the rhombohedral-tetragonal (R-T) phase boundary have suggested an additional lattice distortion induced by poling field. This intermediate phase (IP) is consistent with the orthorhombic (O) symmetry but lower symmetries cannot be discarded. As a result, a modified polarization rotation path along R-IP-T in poled ceramics would be responsible for their high piezoelectric activity owing to the effect of the IP bridging the R and T phases. Simultaneously, the electric field induced phase transition would probably contribute to the observed large piezoelectric strains.

Virtual Fiber Networking and Impact of Optical Path Grooming on Creating Efficient Layer One Services

This paper presents a novel “virtual fiber” network service that exploits wavebands. This service provides virtual direct tunnels that directly convey wavelength paths to connect customer facilities. To improve the resource utilization efficiency of the service, a network design algorithm is developed that can allow intermediate path grooming at limited nodes and can determine the best node location. Numerical experiments demonstrate the effectiveness of the proposed service architecture.

Enabling the 2.5D Integration

3D IC is the viable revolutionary technology that will enable system-level integration, miniaturization, optimal power management, increased data bandwidth, and eventually reduced system cost. Like any breakthrough technologies, it faces many challenges. Design methodology, integration technology, manufacturing process and new industrial ecosystem are the areas of focus. This paper will discuss these challenges and Altera's 3D integration development effort. 2.5D is an intermediate path to true 3D IC using silicon interposer and TSV (Through-Si-Via) stacking. The 2.5D stacking configuration offers different form factor, interconnect path, and thermal management options than monolithic packages, which could help to reduce system level power and thermal management pressure. It offers silicon level interconnect density, low inductive path and wide IO application. However, it's power delivery system (PDN) could be the bottleneck for the system to perform at the intended bandwidth and speed. Thus, the whole system, IC-Interposer-Package-PCB, must be considered holistically, and trade off study and compensation mechanism development are needed in such complex system level integration. There are many different 2.5D integration manufacturing flows currently under development. They can be categorized into two major flow options: Attaching interposer to substrate first, which can be called CoCoS (Chip on Chip on Substrate); or attaching device silicon to interposer first, which is also called CoWoS (Chip on Wafer on Substrate). The major challenges are in the areas of manufacturing process window and yield, thin wafer handling, testability and overall cost of the integration process. ,). This paper will discuss design consideration, manufacturability analysis, Logic/memory devices and silicon interposer interaction, and thermal management to enable the 2.5D integration. System level characterization and correlation with simulations are performed. The challenge of new supply-customer model and industrial ecosystem development associated with 2.5D integration will also be discussed.

Compatibilism and Moral Claimancy: An Intermediate Path to Appropriate Blame

Compatibilism and Moral Claimancy: An Intermediate Path to Appropriate Blame

Molecular Insights into Reprogramming-Initiation Events Mediated by the OSKM Gene Regulatory Network

Somatic cells can be reprogrammed to induced pluripotent stem cells by over-expression of OCT4, SOX2, KLF4 and c-MYC (OSKM). With the aim of unveiling the early mechanisms underlying the induction of pluripotency, we have analyzed transcriptional profiles at 24, 48 and 72 hours post-transduction of OSKM into human foreskin fibroblasts. Experiments confirmed that upon viral transduction, the immediate response is innate immunity, which induces free radical generation, oxidative DNA damage, p53 activation, senescence, and apoptosis, ultimately leading to a reduction in the reprogramming efficiency. Conversely, nucleofection of OSKM plasmids does not elicit the same cellular stress, suggesting viral response as an early reprogramming roadblock. Additional initiation events include the activation of surface markers associated with pluripotency and the suppression of epithelial-to-mesenchymal transition. Furthermore, reconstruction of an OSKM interaction network highlights intermediate path nodes as candidates for improvement intervention. Overall, the results suggest three strategies to improve reprogramming efficiency employing: 1) anti-inflammatory modulation of innate immune response, 2) pre-selection of cells expressing pluripotency-associated surface antigens, 3) activation of specific interaction paths that amplify the pluripotency signal.

Ligand-modulated Parallel Mechanical Unfolding Pathways of Maltose-binding Proteins

Protein folding and unfolding are complex phenomena, and it is accepted that multidomain proteins generally follow multiple pathways. Maltose-binding protein (MBP) is a large (a two-domain, 370-amino acid residue) bacterial periplasmic protein involved in maltose uptake. Despite the large size, it has been shown to exhibit an apparent two-state equilibrium unfolding in bulk experiments. Single-molecule studies can uncover rare events that are masked by averaging in bulk studies. Here, we use single-molecule force spectroscopy to study the mechanical unfolding pathways of MBP and its precursor protein (preMBP) in the presence and absence of ligands. Our results show that MBP exhibits kinetic partitioning on mechanical stretching and unfolds via two parallel pathways: one of them involves a mechanically stable intermediate (path I) whereas the other is devoid of it (path II). The apoMBP unfolds via path I in 62% of the mechanical unfolding events, and the remaining 38% follow path II. In the case of maltose-bound MBP, the protein unfolds via the intermediate in 79% of the cases, the remaining 21% via path II. Similarly, on binding to maltotriose, a ligand whose binding strength with the polyprotein is similar to that of maltose, the occurrence of the intermediate is comparable (82% via path I) with that of maltose. The precursor protein preMBP also shows a similar behavior upon mechanical unfolding. The percentages of molecules unfolding via path I are 53% in the apo form and 68% and 72% upon binding to maltose and maltotriose, respectively, for preMBP. These observations demonstrate that ligand binding can modulate the mechanical unfolding pathways of proteins by a kinetic partitioning mechanism. This could be a general mechanism in the unfolding of other large two-domain ligand-binding proteins of the bacterial periplasmic space.

Shortest paths between shortest paths

We study the following problem on reconfiguring shortest paths in graphs: Given two shortest s – t paths, what is the minimum number of steps required to transform one into the other, where each intermediate path must also be a shortest s – t path and must differ from the previous one by only one vertex. We prove that the shortest reconfiguration sequence can be exponential in the size of the graph and that it is NP-hard to compute the shortest reconfiguration sequence even when we know that the sequence has polynomial length.

The role of the surface structure in the oxidation mechanism of methanol

Pulsed voltammetry has been used to study methanol oxidation in acid media on platinum stepped surfaces to determine the kinetics of the reaction and the role of the surface structure in the reactivity. From the current transients at different potentials, the intrinsic activity of the electrode through the active intermediate reaction path ( j dir,ini), as well as the rate constant for the CO formation ( k ads) and CO oxidation ( k ox) have been calculated. The kinetics for methanol oxidation through the active intermediate reaction path is strongly dependent on the surface structure of the electrode, with the highest activity found for the Pt(1 0 0) surface. The presence of (1 1 1) and (1 0 0) steps, both on (1 0 0) and (1 1 1) terraces, respectively, does not increase the activity of these surfaces, while (1 1 0) steps do improve the catalytic activity. These results are compared to those obtained with formic acid and ethanol to better understand methanol oxidation reaction. Thus, it is obtained that first step in the mechanism is a dehydrogenation step, which is the slowest step in the process. Also, the effect of the anions in the oxidation process is studied.

Robust RBPF-SLAM for Indoor Mobile Robots Using Sonar Sensors in Non-Static Environments

We propose a robust simultaneous localization and mapping (SLAM) with a Rao-Blackwellized particle filter (RBPF) algorithm for mobile robots using sonar sensors in non-static environments. The algorithm consists of three parts: sampling from multiple ancestor sets, estimating intermediate paths for map updates and eliminating spurious landmarks using negative information from sonar sensors. The proposed sampling method, in which particles are sampled from multiple ancestor sets, increases the robustness of the estimation of the robot's pose, even if environmental changes corrupt observations. This step increases the probability of some particles being sampled from correct ancestor sets that are updated by observations reflected from stationary objects. When particles are sampled from several time steps earlier, however, observations at intermediate time steps cannot be used to update the map because of the lack of information about the intermediate path. To update the map with all sensor information, the intermediate path is estimated after particles are sampled from ancestor sets. Finally, spurious landmarks still exist on the map representing objects that were eliminated or that were extracted by error in cluttered areas. These are eliminated in the final step using negative information from the sonar sensors. The performance of the proposed SLAM algorithm was verified through simulations and experiments in various non-static environments.

Novel Application of Structural Equation Modeling to Correlation Structure Analysis of CpG Island Methylation in Colorectal Cancer

The CpG island methylator phenotype (CIMP-high, CIMP1) is a distinct phenotype associated with microsatellite instability (MSI) and BRAF mutation in colon cancer. Recent evidence suggests the presence of KRAS mutation-associated CIMP subtype (CIMP-low, CIMP2). We used cluster analysis, principal component analysis (PCA), and structural equation modeling (SEM), a novel strategy, to decipher the correlation structure of CpG island hypermethylation. Using a database of 861 colon and rectal cancers, DNA methylation at 16 CpG islands [CACNA1G, CDKN2A (p16/ink4a), CHFR, CRABP1, HIC1, IGF2, IGFBP3, MGMT, MINT-1, MINT-31, MLH1, NEUROG1, p14 (CDKN2A/arf), RUNX3, SOCS1, and WRN] was quantified by real-time PCR. Tumors were categorized into three groups: Group 1 with wild-type KRAS/BRAF (N = 440); Group 2 with mutant KRAS and wild-type BRAF (N = 308); and Group 3 with wild-type KRAS and mutant BRAF (N = 107). Tumors with mutant KRAS/BRAF (N = 6) were excluded. In unsupervised hierarchical clustering analysis, all but six markers (CACNA1G, IGF2, RUNX3, MGMT, MINT-1, and SOCS1) were differentially clustered with CIMP-high and CIMP-low according to KRAS and BRAF status. In SEM, the correlation structures between CIMP, locus-specific CpG island methylation, and MSI differed according to KRAS and BRAF status, which was consistent with PCA results. In conclusion, KRAS and BRAF mutations appear to differentially influence correlation structure of CpG island methylation. Our novel data suggest two distinct perturbations, resulting in differential locus-specific propensity of CpG methylation.

Crystallization of Cu 2ZnSnSe 4 compound by solid state reaction using elemental powders

Commercially available elemental Cu, Zn, Sn and Se powders were used to crystallize the stannite-type Cu 2ZnSnSe 4 compound through a solid state reaction. The Cu 2ZnSnSe 4 reaction chemistry was also modeled based on the thermal analysis and X-ray powder diffraction results. Se preferably reacted with Cu to form the α-CuSe and CuSe 2 phases at low reaction temperatures. The formation of the Cu 5Zn 8 intermetallic phase occurred through an intermediate reaction path for the ZnSe formation. At 320 °C, all of the elemental powders completely reacted to form the binary selenides of CuSe, ZnSe and SnSe. The crystallization of Cu 2ZnSnSe 4 began at 300 °C. The compositional investigation of the crystallized Cu 2ZnSnSe 4 compound revealed that the Se loss could not perfectly be avoided during the reaction. The crystallization of Cu 2ZnSnSe 4 occurred through the reaction between Cu 2SnSe 3 and ZnSe.

Formic Acid Oxidation on Shape-Controlled Pt Nanoparticles Studied by Pulsed Voltammetry

Pulsed voltammetry was used to study formic acid electrooxidation on Pt nanoparticles with well-characterized surfaces. Polyoriented and preferential (100), (100−111), and (111) Pt nanoparticles were characterized and employed to evaluate the influence of the surface structure and shape of the Pt nanoparticles on this model electrochemical reaction. The results pointed out that, in agreement with fundamental studies with Pt single crystal electrodes, the surface structure of the electrodes plays an important role on the reactivity and kinetics of formic acid oxidation. Thus the electrocatalytic properties for this reaction strongly depend on the dominant structure on the surface of the nanoparticles, in particular on the presence of domains with (100) and (111) symmetry. Among the Pt nanoparticles studied, those containing (100) domains are clearly the most active toward formic acid electrooxidation via the active intermediate path, but also exhibit the highest poisoning rate. (111) Pt nanoparticles show ...

Arithmetic and aging: Impact of quantitative knowledge and processing speed

The main objective of this study was to examine how quantitative knowledge ( Gq in the CHC model) and processing speed ( Gs in the CHC model) affect scores on the WAIS-III Arithmetic Subtest (Wechsler, 2000) with aging. Two age groups were compared: 30 young adults and 25 elderly adults. For both age groups, Gq was an important predictor of Arithmetic score variance ( R² = 48% and R² = 45%, respectively). However, in line with Salthouse, the results showed that processing speed predicted Arithmetic scores only for the older adults, not for the younger ones (additional 9% of the variance for the elderly vs. 1% of the variance for the young adults). These results can clarify the ambiguous evolution of Arithmetic scores with aging: Arithmetic performance with aging seems to follow an intermediate path between Gc and Gf. This suggests that both Gq and Gs have an impact on Arithmetic in aging.

Intermartensitic transformation and magnetic field effect in NiMnInSb ferromagnetic shape memory alloys

Partially substituting Sb for In, we found an irreversible transformation of martensite to intermartensite at 90 K in Ni 50Mn 34In 12Sb 4 alloy during heating. The reverse transformation of martensite and intermartensite to the parent phase induced by a magnetic field has been investigated. The results indicate that, if a sufficiently high magnetic field is applied, the intermartensite state is no longer necessary as an intermediate state. Thus, a difference of the transformation originating from magnetic and from thermal energies has been found. In this competition, lattice distortions play an important role to promote the occurrence of the intermediate intermartensitic path.

Intrinsic activity and poisoning rate for HCOOH oxidation on platinum stepped surfaces

Pulsed voltammetry has been used to study formic acid oxidation on platinum stepped surfaces to determine the kinetics of the reaction and the role of the surface structure in the reactivity. From the current transients at different potentials, the intrinsic activity of the electrode through the active intermediate reaction path (j(theta = 0)), as well as the rate constant for the CO formation (k(ads)) have been calculated. The kinetics for formic acid oxidation through the active intermediate reaction path is strongly dependent on the surface structure of the electrode, with the highest activity found for the Pt(100) surface. The presence of steps, both on (100) and (111) terraces, does not increase the activity of these surfaces. CO formation only takes place in a narrow potential window very close to the local potential of zero total charge. The extrapolation of the results obtained with stepped surfaces with (111) terraces to zero step density indicates that CO formation should not occur on an ideal Pt(111) electrode. Additionally, the analysis of the Tafel slopes obtained for the different electrodes suggests that the oxidation of formic acid is strongly affected by the presence of adsorbed anions, hydrogen and water.

Intrinsic Activity and Poisoning Rate for HCOOH Oxidation at Pt(100) and Vicinal Surfaces Containing Monoatomic (111) Steps

Pulsed voltammetry is used to study formic acid oxidation on Pt(2n-1,1,1) surfaces and determine the effects of the size of the (100) terrace and the (111) step density on the reaction mechanism. The intrinsic activity of the electrode through the active intermediate reaction path (j(theta=) (0)), as well as the rate constant for the CO formation (k(ads)), are calculated from the current transients obtained at different potentials. For surfaces with wide terraces, j(theta=) (0) and k(ads) are almost insensitive to the step density, which suggests that step and terrace sites have a similar activity for this reaction. For narrow terraces (n<6), the intrinsic activity diminishes. The dependence of the reaction rates on the electrode potential is also elucidated. The CO formation only takes place in a narrow potential window, very close to the potential of zero total charge, while the direct oxidation takes place even when the surface is covered by anions. The different behavior for both reactions suggests that the adsorption mode of formic acid is different for each path.

Evolution of Concentration Profiles and Diffusion Paths in Single-Phase Multicomponent Multilayered Assemblies

An analysis of multilayered assemblies set up with multicomponent alloys selected in a single phase field has been recently developed on the basis of a matrix of constant interdiffusion coefficients. This analysis employs a transfer matrix method and is applicable to a study of evolution of concentration profiles and diffusion paths as a function of time for multilayered diffusion assemblies (MDAs) where any number of finite layers is sandwiched between two bulk terminal alloys. The analysis is utilized in this study to simulate concentration profiles and diffusion paths for MDAs assembled with (fcc) Cu-Ni-Zn alloys with two terminal alloys, A and B, sandwiching an alloy layer C in the middle. For short diffusion times the diffusion path of the ternary MDA, A/C/B, corresponds to two segments corresponding to the diffusion paths of the infinite diffusion couples, A/C and C/B. At longer times the diffusion zones of the two individual couples overlap and the diffusion path of the MDA varies continuously with time. The evolution of the concentration profiles and diffusion paths is presented and each intermediate path configuration is associated with a unique ratio of the middle layer thickness to the square root of diffusion time. The simulated concentration profiles clearly show the development of uphill diffusion and zero-flux planes (ZFP) for the individual components due to diffusional interactions among the components. At very long times, the diffusion path of the MDA approaches that of the infinite couple A/B between the two terminal alloys.

The three worlds of post-communism: revisiting deep and proximate explanations

Since the upheavals of 1989–1991, the post-communist countries have embarked upon three distinct political trajectories: a path leading to democracy in the Western part of the setting, a path leading to autocracy in the Eastern part of the setting, and an intermediate path – both in geographical and political terms – leading to ‘defective’ democracy. This article seeks to explain the emergence of these three worlds of post-communism. Using typological theory as the principal methodological tool, we revisit Herbert Kitschelt's distinction between deep (structural) and proximate (actor-centred) explanations. The empirical results show that the post-communist setting is characterized by striking regularities in the form of clustering in the explanandum as well as the explanans. The orderings of referents on both the deep and the proximate attributes show a remarkable co-variation with the political pathways of post-communism – and with each other. The presence of such systematic empirical regularities lends support to two conclusions. First, both kinds of explanations elucidate the present variation in post-communist political regime types. Second, the variation on the deep factors largely explains the variation on the proximate factors. Kitschelt's general plea to dig deeper is thus supported, and the explanatory quest turns into a challenge of theoretical integration.