Is there a higher genetic load of susceptibility loci in familial ankylosing spondylitis?

Objective Several genetic risk variants for ankylosing spondylitis (AS) have been identified in genome-wide association studies. Our objective was to examine whether familial AS cases have a higher genetic load of these susceptibility variants. Methods Overall, 502 AS patients were examined, consisting of 312 patients who had first-degree relatives (FDRs) with AS (familial) and 190 patients who had no FDRs with AS or spondylarthritis (sporadic). All patients and affected FDRs fulfilled the modified New York criteria for AS. The patients were recruited from 2 US cohorts (the North American Spondylitis Consortium and the Prospective Study of Outcomes in Ankylosing Spondylitis) and from the UK-Oxford cohort. The frequencies of AS susceptibility loci in IL-23R, IL1R2, ANTXR2, ERAP-1, 2 intergenic regions on chromosomes 2p15 and 21q22, and HLA-B27 status as determined by the tag single-nucleotide polymorphism (SNP) rs4349859 were compared between familial and sporadic cases of AS. Association between SNPs and multiplex status was assessed by logistic regression controlling for sibship size. Results HLA-B27 was significantly more prevalent in familial than sporadic cases of AS (odds ratio 4.44 [95% confidence interval 2.06, 9.55], P = 0.0001). Furthermore, the AS risk allele at chromosome 21q22 intergenic region showed a trend toward higher frequency in the multiplex cases (P = 0.08). The frequency of the other AS risk variants did not differ significantly between familial and sporadic cases, either individually or combined. Conclusion HLA-B27 is more prevalent in familial than sporadic cases of AS, demonstrating higher familial aggregation of AS in patients with HLA-B27 positivity. The frequency of the recently described non-major histocompatibility complex susceptibility loci is not markedly different between the sporadic and familial cases of AS.

Whole exome sequencing is an efficient and sensitive method for detection of germline mutations in patients with phaeochromcytomas and paragangliomas

Background Genetic testing is recommended when the probability of a disease-associated germline mutation exceeds 10%. Germline mutations are found in approximately 25% of individuals with phaeochromcytoma (PCC) or paraganglioma (PGL); however, genetic heterogeneity for PCC/PGL means many genes may require sequencing. A phenotype-directed iterative approach may limit costs but may also delay diagnosis, and will not detect mutations in genes not previously associated with PCC/PGL. Objective To assess whether whole exome sequencing (WES) was efficient and sensitive for mutation detection in PCC/PGL. Methods Whole exome sequencing was performed on blinded samples from eleven individuals with PCC/PGL and known mutations. Illumina TruSeq™ (Illumina Inc, San Diego, CA, USA) was used for exome capture of seven samples, and NimbleGen SeqCap EZ v3.0 (Roche NimbleGen Inc, Basel, Switzerland) for five samples (one sample was repeated). Massive parallel sequencing was performed on multiplexed samples. Sequencing data were called using Genome Analysis Toolkit and annotated using annovar. Data were assessed for coding variants in RET, NF1, VHL, SDHD, SDHB, SDHC, SDHA, SDHAF2, KIF1B, TMEM127, EGLN1 and MAX. Target capture of five exome capture platforms was compared. Results Six of seven mutations were detected using Illumina TruSeq™ exome capture. All five mutations were detected using NimbleGen SeqCap EZ v3.0 platform, including the mutation missed using Illumina TruSeq™ capture. Target capture for exons in known PCC/PGL genes differs substantially between platforms. Exome sequencing was inexpensive (<$A800 per sample for reagents) and rapid (results <5 weeks from sample reception). Conclusion Whole exome sequencing is sensitive, rapid and efficient for detection of PCC/PGL germline mutations. However, capture platform selection is critical to maximize sensitivity.

SnO2 decorated graphene nanocomposite anode materials prepared via an up-scalable wet-mechanochemical process for sodium ion batteries

A facile and up-scalable wet-mechanochemical process is designed for fabricating ultra-fine SnO2 nanoparticles anchored on graphene networks for use as anode materials for sodium ion batteries. A hierarchical structure of the SnO2@graphene composite is obtained from the process. The resultant rechargeable SIBs achieved high rate capability and good cycling stability.

Plasma-enabled carbon nanostructures for early diagnosis of neurodegenerative diseases

Carbon nanostructures (CNs) are amongst the most promising biorecognition nanomaterials due to their unprecedented optical, electrical and structural properties. As such, CNs may be harnessed to tackle the detrimental public health and socio-economic adversities associated with neurodegenerative diseases (NDs). In particular, CNs may be tailored for a specific determination of biomarkers indicative of NDs. However, the realization of such a biosensor represents a significant technological challenge in the uniform fabrication of CNs with outstanding qualities in order to facilitate a highly-sensitive detection of biomarkers suspended in complex biological environments. Notably, the versatility of plasma-based techniques for the synthesis and surface modification of CNs may be embraced to optimize the biorecognition performance and capabilities. This review surveys the recent advances in CN-based biosensors, and highlights the benefits of plasma-processing techniques to enable, enhance, and tailor the performance and optimize the fabrication of CNs, towards the construction of biosensors with unparalleled performance for the early diagnosis of NDs, via a plethora of energy-efficient, environmentally-benign, and inexpensive approaches.

Surface materials and aspects of care: A study in modes of being in a visual art practice

Through creative practice and written research, this thesis explores the peculiar qualities of surface materials, revealing a broader ethos of practice which I identify as care. I propose that care arises as a mode of being between artist and work, work and beholder, and between the parts of the work. The thesis situates the art practice within an ethical framework, premised on, but extending, Heidegger's ontological equation of care with being. The original contribution is in the claim that the particular qualities of worldly matter generate the terms for care as a particular mode of engagement that is reciprocal and intransitive.

Measuring load of phosphate in the environment by passive sampling techniques: An introduction

Phosphorus has a number of indispensable biochemical roles, but its natural deposition and the low solubility of phosphates as well as their rapid transformation to insoluble forms make the element commonly the growth-limiting nutrient, particularly in aquatic ecosystems. Famously, phosphorus that reaches water bodies is commonly the main cause of eutrophication. This undesirable process can severely affect many aquatic biotas in the world. More management practices are proposed but long-term monitoring of phosphorus level is necessary to ensure that the eutrophication won't occur. Passive sampling techniques, which have been developed over the last decades, could provide several advantages to the conventional sampling methods including simpler sampling devices, more cost-effective sampling campaign, providing flow proportional load as well as representative average of concentrations of phosphorus in the environment. Although some types of passive samplers are commercially available, their uses are still scarcely reported in the literature. In Japan, there is limited application of passive sampling technique to monitor phosphorus even in the field of agricultural environment. This paper aims to introduce the relatively new P-sampling techniques and their potential to use in environmental monitoring studies.

Loading compliance of static load bearing exercises performed by transfemoral amputees fitted with an osseointegrated implant

Background To date bone-anchored prostheses are used to alleviate the concerns caused by socket suspended prostheses and to improve the quality of life of transfemoral amputees (TFA). Currently, two implants are commercially available (i.e., OPRA (Integrum AB, Sweden), ILP (Orthodynamics GmbH, Germany)). [1-17]The success of the OPRA technique is codetermined by the rehabilitation program. TFA fitted with an osseointegrated implant perform progressive mechanical loading (i.e. static load bearing exercises (LBE)) to facilitate bone remodelling around the implant.[18, 19] Aim This study investigated the trustworthiness of monitoring the load prescribed (LP) during experimental static LBEs using the vertical force provided by a mechanical bathroom scale that is considered a surrogate of the actual load applied. Method Eleven unilateral TFAs fitted with an OPRA implant performed five trials in four loading conditions. The forces and moments on the three axes of the implant were measured directly with an instrumented pylon including a six-channel transducer. The “axial” and “vectorial” comparisons corresponding to the difference between the force applied on the long axis of the fixation and LP as well as the resultant of the three components of the load applied and LP, respectively were analysed Results For each loading condition, Wilcoxon One-Sample Signed Rank Tests were used to investigate if significant differences (p<0.05) could be demonstrated between the force applied on the long axis and LP, and between the resultant of the force and LP. The results demonstrated that the raw axial and vectorial differences were significantly different from zero in all conditions (p<0.05), except for the vectorial difference for the 40 kg loading condition (p=0.182). The raw axial difference was negative for all the participants in every loading condition, except for TFA03 in the 10 kg condition (11.17 N). Discussion & Conclusion This study showed a significant lack of axial compliance. The load applied on the long axis was significantly smaller than LP in every loading condition. This led to a systematic underloading of the long axis of the implant during the proposed experimental LBE. Monitoring the vertical force might be only partially reflective of the actual load applied, particularly on the long axis of the implant.

A new load distribution strategy for linear network with communication delays

In this paper, we propose a new load distribution strategy called `send-and-receive' for scheduling divisible loads, in a linear network of processors with communication delay. This strategy is designed to optimally utilize the network resources and thereby minimizes the processing time of entire processing load. A closed-form expression for optimal size of load fractions and processing time are derived when the processing load originates at processor located in boundary and interior of the network. A condition on processor and link speed is also derived to ensure that the processors are continuously engaged in load distributions. This paper also presents a parallel implementation of `digital watermarking problem' on a personal computer-based Pentium Linear Network (PLN) topology. Experiments are carried out to study the performance of the proposed strategy and results are compared with other strategies found in literature.

Bearing capacity of cold-formed unlipped channels with restrained flanges under EOF and IOF load cases

Bearing failure is a form of localized failure that occurs when thin-walled cold-formed steel sections are subjected to concentrated loads or support reactions. To determine the bearing capacity of cold-formed channel sections, a unified design equation with different bearing coefficients is given in the current North American specification AISI S100 and the Australian/New Zealand standard AS/NZS 4600. However, coefficients are not available for unlipped channel sections that are normally fastened to supports through their flanges. Eurocode 3 Part 1.3 includes bearing capacity equations for different load cases, but does not distinguish between fastened and unfastened support conditions. Therefore, an experimental study was conducted to determine the bearing capacities of these sections as used in floor systems. Twenty-eight web bearing tests on unlipped channel sections with restrained flanges were conducted under End One Flange (EOF) and Interior One Flange (IOF) load cases. Using the results from this study, a new equation was proposed within the AISI S100 and AS/NZS 4600 guidelines to determine the bearing capacities of cold-formed unlipped channels with flanges fastened to supports. A new design rule was also proposed based on the direct strength method.

ELISA: An Estimated Load Information Scheduling Algorithm for Distributed Computing Systems

In this paper, we present a decentralized dynamic load scheduling/balancing algorithm called ELISA (Estimated Load Information Scheduling Algorithm) for general purpose distributed computing systems. ELISA uses estimated state information based upon periodic exchange of exact state information between neighbouring nodes to perform load scheduling. The primary objective of the algorithm is to cut down on the communication and load transfer overheads by minimizing the frequency of status exchange and by restricting the load transfer and status exchange within the buddy set of a processor. It is shown that the resulting algorithm performs almost as well as a perfect information algorithm and is superior to other load balancing schemes based on the random sharing and Ni-Hwang algorithms. A sensitivity analysis to study the effect of various design parameters on the effectiveness of load balancing is also carried out. Finally, the algorithm's performance is tested on large dimensional hypercubes in the presence of time-varying load arrival process and is shown to perform well in comparison to other algorithms. This makes ELISA a viable and implementable load balancing algorithm for use in general purpose distributed computing systems.

An Efficient Load Distribution Strategy for a Distributed Linear Network of Processors with Communication Delays

In this paper, we present an improved load distribution strategy, for arbitrarily divisible processing loads, to minimize the processing time in a distributed linear network of communicating processors by an efficient utilization of their front-ends. Closed-form solutions are derived, with the processing load originating at the boundary and at the interior of the network, under some important conditions on the arrangement of processors and links in the network. Asymptotic analysis is carried out to explore the ultimate performance limits of such networks. Two important theorems are stated regarding the optimal load sequence and the optimal load origination point. Comparative study of this new strategy with an earlier strategy is also presented.

Studies on elastic coupling parameters of fracture modes in orthotropic materials

The characterisation of cracks is usually done using the well known three basic fracture modes, namely opening, shearing and tearing modes. In isotropic materials these modes are uncoupled and provide a convenient way to define the fracture parameters. It is well known that these fracture modes are coupled in anisotropic materials. In the case of orthotropic materials also, coupling exists between the fracture modes, unless the crack plane coincides with one of the axes of orthotropy. The strength of coupling depends upon the orientation of the axes of orthotropy with respect to the crack plane and so the energy release rate components associated with each of the modes vary with crack orientation. The variation, of these energy release rate components with the crack orientation with respect to orthotropic axes, is analyzed in this paper. Results indicate that in addition to the orthotropic planes there exists other planes with reference to which fracture modes are uncoupled.

The high temperature mechanical characteristics of superplastic 3 mol% yttria stabilized zirconia

A detailed study was undertaken to characterize the deformation behavior of a superplastic 3 mol% yttria-stabilized tetragonal zirconia (3YTZ) over a wide range of strain rates, temperatures and grain sizes. The experimental data were analyzed in terms of the following equation for high temperature deformation: Image Full-size image ∞ σn d−pexp(−Q/RT), where Image Full-size image is the strain rate, σ is the flow stress, d is the grain size, Q is the activation energy, R is the gas constant, T is the absolute temperature, and n and p are constants termed the stress exponent and the inverse grain size exponent, respectively. The experimental data over a wide range of stresses revealed a transition in stress exponent. Deformation in the low and high stress regions was associated with n not, vert, similar 3 and p not, vert, similar 1, and n not, vert, similar 2 and p not, vert, similar 3, respectively. The transition stress between the two regions decreased with increasing grain size. The activation energy was similar for both regions with a value of not, vert, similar 550 kJ mol−1. Microstructural measurements revealed that grains remained essentially equiaxed after the accumulation of large strains, and very limited concurrent grain growths occurred in most experiments. Assessment of possible rate controlling creep mechanisms and comparison with previous studied indicate that in the n not, vert, similar 2 region, deformation occurs by a grain boundary sliding process whose rate is independent of impurity content. Deformation in the n not, vert, similar 3 region is controlled by an interface reaction that is highly sensitive to impurity content. It is concluded that an increase in impurity content increases yttrium segregation to grain boundaries, which enhances the rate of the interface reaction, thereby decreasing the apparent transition stress between the n not, vert, similar 2 and n not, vert, similar 3 regions. This unified approach incorporating two sequential mechanisms can rationalize many of the apparently dissimilar results that have been reported previously for deformation of 3YTZ.

The influence of trace impurities on the mechanical characteristics of a superplastic 2 mol% yttria stabilized zirconia

In contrast to metallic alloys, the mechanical characteristics of superplastic ceramics are very sensitive to minor changes in levels of trace impurities. In the present study, the mechanical behavior of a 2 mol% yttria stabilized tetragonal zirconia was studied in tension and compression in two batches of material, with small variations in levels of trace impurities, to examine the influence of stress axis and impurity content on the deformation behavior. The mechanical properties of the material were characterized in terms of the expression: (epsilon)over dot proportional to sigma(n) where (epsilon)over dot is the strain rate, sigma is the stress and n is termed the stress exponent. The mechanical behavior of the ceramic was identical in tension and compression, for a material with a given level of impurity. The high purity specimens exhibited a transition from a stress exponent of similar to 3 to similar to 2 with an increase in stress, whereas the low purity material displayed only n similar to 2 behavior over the entire stress range studied. Detailed high resolution and analytical electron microscopy studies revealed that there was no amorphous phase at interfaces in both batches of material; however, segregation of Al at interfaces was detected only in the low purity material. The observed transition in stress exponents can be rationalized in terms of two sequential mechanisms: grain boundary sliding with n similar to 2 and interface reaction controlled grain boundary sliding with n similar to 3. The transition from n similar to 3 to similar to 2 occurred at lower stresses with an increase in the grain size and a decrease in the purity level.

Yielding of sensitive clays: micromechanical considerations

Test results reported on several natural sensitive soils show significant anisotropy of the yield curves, which are generally oriented along the coefficient of earth pressure at rest (K-0) axis. An attempt is made in this paper to explain the anisotropy in yielding from microstructural considerations. An elliptic pore, with particle domains aligned along the periphery of the pore, and with the major axis of the pore being oriented along the direction of the in situ major principal stress, is chosen as the unit of microstructure. An analysis of forces at the interdomain contacts around the ellipse is carried out with reference to experimentally determined yield stress conditions of one soil, and a yield criteria is defined. The analysis, with the proposed yield criteria, enables one to define the complete yield curve for any other soil from the results of only two tests (one constant eta compression test with eta close to eta(K?0), where eta is the stress ratio (= q/p) and eta(K?0) is the stress ratio corresponding to anisotropic K-0 compression, and another undrained shear test). Predicted yield curves are compared with experimental yield curves of several soils reported in the literature.