Association Study of 167 Candidate Genes for Schizophrenia Selected by a Multi-Domain Evidence-Based Prioritization Algorithm and Neurodevelopmental Hypothesis

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this
ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted.

Is Use of Optional Attributes and Associations in Conceptual Modeling Always Problematic? Theory and Empirical Tests

Prior research has argued that use of optional properties in conceptual models results in loss of information about the semantics of the domains represented by the models. Empirical research undertaken to date supports this argument. Nevertheless, no systematic analysis has been done of whether use of optional properties is always problematic. Furthermore, prior empirical research might have deliberately or unwittingly employed models where use of optionality always causes problems. Accordingly, we examine analytically whether use of optional properties is always problematic. We employ our analytical results to inform the design of an experiment where we systematically examined the impact of optionality on users’ ability to understand domains represented by different types of conceptual models. We found evidence that use of optionality undermines users’ ability to understand the domain represented by a model but that this effect weakens when use of mandatory properties to replace optional properties leads to more-complex models.

‘CLAM’ tests for measuring in-situ permeation properties of concrete

This paper descirbes a simple test measuring the sorptivity (a measure of the absorption property if concrete) and the air and water permeability of concrete on site. Using this test, the decay of pressure is monitired for the air permeability test.whereas water penetrating into the concrete at a constant pressure of 0.01 bar and 1.5 bar are recorded for the sorptivity and the water permeability tests respectively. These tests are essentially non-destructive in nature and a skilled operator is not needed. It is possible to carry out a number of tests quickly and efficiently on site without prior planning. It has been found that statistically satisfactory results can be obtained from a mean of three tests. As the flow lines are largely concentrated within 40 mm from the surface, reasonably reliable results can be obtained by drying the surface even if the surface under test is initially wet.

Using macroscopic entanglement to close the detection loophole in Bell-inequality tests

We consider a Bell-like inequality performed using various instances of multiphoton entangled states to demonstrate that losses occurring after the unitary transformations used in the nonlocality test can be counteracted by enhancing the size of such entangled states. In turn, this feature can be used to overcome detection inefficiencies affecting the test itself: a slight increase in the size of such states, pushing them towards a more macroscopic form of entanglement, significantly improves the state robustness against detection inefficiency, thus easing the closing of the detection loophole. Differently, losses before the unitary transformations cause decoherence effects that cannot be compensated using macroscopic entanglement.

Commissioning and Evaluation of a Fiber-Optic Sensor System for Bridge Monitoring

This paper describes the design, commissioning, and evaluation of a ?ber-optic strain sensor system for the structural health monitoring of a prestressed concrete posttensioned box girder railway bridge in Mumbai, India, which shows a number of well-documented structural problems. Preliminary laboratory trials to design the most appropriate sensor system that could be readily transported and used on site are described, followed by a description of load tests on the actual bridge undertaken in collaboration with Indian Railways and using locomotives of known weight. Results from the load tests using the optical system are compared with similar results obtained using electrical resistance strain gages. Conclusions are summarized concerning the integrity of the structure and for the future use of the sensor system for monitoring bridges of this type. Crack width measurements obtained during the load tests are also described.

Screw conveyor device for laboratory tests on conditioned soil for EPB tunneling operations

Earth pressure balanced (EPB) full face tunneling machines have experienced a remarkable increase in the number of applications throughout the world due to both mechanical developments and a more effective use of additives to condition the ground. Conditioning modifies the mechanical and hydraulic properties of a soil by making it suitable for the pressure control in the bulk chamber and extraction with the screw conveyor. The extraction system plays a fundamental role during the EPB operations particularly for a correct application of the face pressure. Despite the extensive use of the EPB technique, little knowledge exists concerning the understanding of the behavior of conditioned soil, particularly for noncohesive ground (sand and gravel). This paper presents and describes a prototype laboratory device, which simulates the extraction of the ground from a pressurized tank with a screw conveyor. The results of a preliminary test program carried out on a medium sized sand show that the prototype device is efficient in verifying the effects of foam for an optimal use in EPB conditioning. © 2007 ASCE.

Laboratory tests for EPB tunnelling soil conditioning

The screw conveyor system plays a fundamental role during the EPB tunnelling operations for the tunnel face pressure control. On the other hand, the use of additives such chemical foams is even more applied in order to extend the EPB technology to the cohesionless soils. Despite the extensive use of the EPB technique in urban environment, little knowledge exists in the understanding of the behavior of such conditioned soil during the excavation operations. At the Turin University of Technology the Tunnelling and Underground Space Centre, in the mainframe of a wider research on soil conditioning, has developed an experimental apparatus that simulates the extraction phase with screw conveyor from a pressurized tank. In this paper the apparatus is presented and the results of a first series of tests carried out on sand are discussed. © 2007 Taylor & Francis Group.

Soil conditioning of sand for EPB applications:A laboratory research

EPB tunnelling requires the application of soil conditioning to increase its field of applicability particularly for cohesionless soils. Choosing the most suitable conditioning set for the various soils requires the use of a feasible laboratory test which can permit to define the characteristics of the conditioned soils and provide measurable data. A series of tests has been carried out using a laboratory screw conveyor device which was designed for this purpose and which simulates the extraction of the spoil from a pressure chamber in a similar way as in EPB tunnelling. The tested soils were medium-grain sands with varying amounts of silt and the tested conditioned mixtures were obtained with different water contents and amounts of foam. A simple slump test was also used to analyze the global characteristics of the conditioned soils. The test has shown that the proposed laboratory procedure permits a quantitative comparison to be made between different conditioning amounts and agents on the basis of measurable parameters. © 2007 Elsevier Ltd. All rights reserved.

Laboratory tests to study the influence of rock stress confinement on the performances of TBM discs in tunnels

To clarify some aspects of rock destruction with a disc acting on a high confined tunnel face, a series of tests were carried out to examine fracture mechanisms under an indenter that simulates the tunnel boring machine (TBM) tool action, in the presence of an adjacent groove, when a state of stress (lateral confinement) is imposed on a rock sample. These tests proved the importance of carefully establishing the optimal distance of grooves produced by discs acting on a confined surface, and the value (as a mere order of magnitude) of the increase of the thrust to produce the initiation of chip formation, as long as the confinement pressure becomes greater. © University of Science and Technology Beijing and Springer-Verlag Berlin Heidelberg 2011.

Numerical modelling of laboratory tests for TBM cutter indentation process analysis

Considering that TBMs are nowadays used for long Trans-Alpine tunnels, the
understanding of rock breaking and chipping due to TBM cutter disks mechanism, for deep tunnelling operations, becomes very interesting. In this paper, the results from carried out laboratory tests that simulate the disk cutter action at the rock tunnel face by means of an indentation tool, acting on a rock
specimen with proper size, and the related three-dimensional and two-dimensional numerical modelling are proposed. The developed numerical models simulate the different test conditions (applied load, boundary conditions) allowing the analysis of the stresses distributions along possible breaking planes.
The influence of a confinement-free area on one side of the specimen, simulating the formation of a groove near the tool, is pointed out.
The obtained results from numerical modelling put in evidence a satisfactory agreement with the experimental observations.

Mutations within subdomain II of the extracellular region of epidermal growth factor receptor selectively alter TGF alpha binding

The interactions of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) with the epidermal growth factor receptor (EGFR) were examined by insertion mutagenesis of the receptor. Seventeen insertions were made throughout a construct containing only the extracellular domain. This truncated receptor (sEGFR) was secreted and had a dissociation constant similar to that of the full-length solubilized receptor. Receptors with insertions within subdomain III were not secreted. Two receptors with insertions at positions 291 and 474, which border subdomain III, have significantly decreased binding to both EGF and TGF alpha relative to wild type. This confirms previous work demonstrating that subdomain III forms the primary binding site for EGF and TGF alpha. Four of the mutants within subdomain II had a decreased binding to TGF alpha relative to wild type, but had wild type binding to EGF. These results suggest that a region within subdomain II may selectively regulate the binding of TGF alpha. Two receptors which contained insertions within subdomains II and IV, approximately equidistant from the center of subdomain III, bound twofold more ligand molecules than wild type receptor, with an affinity similar to that of wild type receptor. These findings suggest that insertion at these positions allows the access of more than one ligand molecule to the binding site.

Early Holocene M similar to 6 explosive eruption from Plosky volcanic massif (Kamchatka) and its tephra as a link between terrestrial and marine paleoenvironmental records

We report tephrochronological and geochemical data on early Holocene activity from Plosky volcanic massif in the Kliuchevskoi volcanic group, Kamchatka Peninsula. Explosive activity of this volcano lasted for similar to 1.5 kyr, produced a series of widely dispersed tephra layers, and was followed by profuse low-viscosity lava flows. This eruptive episode started a major reorganization of the volcanic structures in the western part of the Kliuchevskoi volcanic group. An explosive eruption from Plosky (M similar to 6), previously unstudied, produced tephra (coded PL2) of a volume of 10-12 km(3) (11-13 Gt), being one of the largest Holocene explosive eruptions in Kamchatka. Characteristic diagnostic features of the PL2 tephra are predominantly vitric sponge-shaped fragments with rare phenocrysts and microlites of plagioclase, olivine and pyroxenes, medium- to high-K basaltic andesitic bulk composition, high-K, high-Al and high-P trachyandesitic glass composition with SiO2 = 57.5-59.5 wt%, K2O = 2.3-2.7 wt%, Al2O3 = 15.8-16.5 wt%, and P2O5 = 0.5-0.7 wt%. Other diagnostic features include a typical subduction-related pattern of incompatible elements, high concentrations of all REE (> 10x mantle values), moderate enrichment in LREE (La/Yb similar to 5.3), and non-fractionated mantle-like pattern of LILE. Geochemical fingerprinting of the PL2 tephra with the help of EMP and LA-ICP-MS analyses allowed us to map its occurrence in terrestrial sections across Kamchatka and to identify this layer in Bering Sea sediment cores at a distance of > 600 km from the source. New high-precision C-14 dates suggest that the PL2 eruption occurred similar to 10,200 cal BP, which makes it a valuable isochrone for early Holocene climate fluctuations and permits direct links between terrestrial and marine paleoenvironmental records. The terrestrial and marine C-14 dates related to the PL2 tephra have allowed us to estimate an early Holocene reservoir age for the western Bering Sea at 1,410 +/- A 64 C-14 years. Another important tephra from the early Holocene eruptive episode of Plosky volcano, coded PL1, was dated at 11,650 cal BP. This marker is the oldest geochemically characterized and dated tephra marker layer in Kamchatka to date and is an important local marker for the Younger Dryas-early Holocene transition. One more tephra from Plosky, coded PL3, can be used as a marker northeast of the source at a distance of similar to 110 km.

The presence of a culturally similar or dissimilar social partner affects neural responses to emotional stimuli

Background: Emotional responding is sensitive to social context; however, little emphasis has been placed on the mechanisms by which social context effects changes in emotional responding.

Objective: We aimed to investigate the effects of social context on neural responses to emotional stimuli to inform on the mechanisms underpinning context-linked changes in emotional responding.

Design: We measured event-related potential (ERP) components known to index specific emotion processes and self-reports of explicit emotion regulation strategies and emotional arousal. Female Chinese university students observed positive, negative, and neutral photographs, whilst alone or accompanied by a culturally similar (Chinese) or dissimilar researcher (British).

Results: There was a reduction in the positive versus neutral differential N1 amplitude (indexing attentional capture by positive stimuli) in the dissimilar relative to alone context. In this context, there was also a corresponding increase in amplitude of a frontal late positive potential (LPP) component (indexing engagement of cognitive control resources). In the similar relative to alone context, these effects on differential N1 and frontal LPP amplitudes were less pronounced, but there was an additional decrease in the amplitude of a parietal LPP component (indexing motivational relevance) in response to positive stimuli. In response to negative stimuli, the differential N1 component was increased in the similar relative to dissimilar and alone (trend) context.

Conclusion: These data suggest that neural processes engaged in response to emotional stimuli are modulated by social context. Possible mechanisms for the social-context-linked changes in attentional capture by emotional stimuli include a context-directed modulation of the focus of attention, or an altered interpretation of the emotional stimuli based on additional information proportioned by the context.