Patient-Specific Prosthetic Fingers by Remote Collaboration - A Case Study

The concealment of amputation through prosthesis usage can shield an amputee from social stigma and help improve the emotional healing process especially at the early stages of hand or finger loss. However, the traditional techniques in prosthesis fabrication defy this as the patients need numerous visits to the clinics for measurements, fitting and follow-ups. This paper presents a method for constructing a prosthetic finger through online collaboration with the designer. The main input from the amputee comes from the Computer Tomography (CT) data in the region of the affected and the non-affected fingers. These data are sent over the internet and the prosthesis is constructed using visualization, computer-aided design and manufacturing tools. The finished product is then shipped to the patient. A case study with a single patient having an amputated ring finger at the proximal interphalangeal joint shows that the proposed method has a potential to address the patient's psychosocial concerns and minimize the exposure of the finger loss to the public.Comment: Open Access articl

Error, reproducibility and sensitivity : a pipeline for data processing of Agilent oligonucleotide expression arrays

Background Expression microarrays are increasingly used to obtain large scale transcriptomic information on a wide range of biological samples. Nevertheless, there is still much debate on the best ways to process data, to design experiments and analyse the output. Furthermore, many of the more sophisticated mathematical approaches to data analysis in the literature remain inaccessible to much of the biological research community. In this study we examine ways of extracting and analysing a large data set obtained using the Agilent long oligonucleotide transcriptomics platform, applied to a set of human macrophage and dendritic cell samples. Results We describe and validate a series of data extraction, transformation and normalisation steps which are implemented via a new R function. Analysis of replicate normalised reference data demonstrate that intrarray variability is small (only around 2% of the mean log signal), while interarray variability from replicate array measurements has a standard deviation (SD) of around 0.5 log2 units ( 6% of mean). The common practise of working with ratios of Cy5/Cy3 signal offers little further improvement in terms of reducing error. Comparison to expression data obtained using Arabidopsis samples demonstrates that the large number of genes in each sample showing a low level of transcription reflect the real complexity of the cellular transcriptome. Multidimensional scaling is used to show that the processed data identifies an underlying structure which reflect some of the key biological variables which define the data set. This structure is robust, allowing reliable comparison of samples collected over a number of years and collected by a variety of operators. Conclusions This study outlines a robust and easily implemented pipeline for extracting, transforming normalising and visualising transcriptomic array data from Agilent expression platform. The analysis is used to obtain quantitative estimates of the SD arising from experimental (non biological) intra- and interarray variability, and for a lower threshold for determining whether an individual gene is expressed. The study provides a reliable basis for further more extensive studies of the systems biology of eukaryotic cells

Multivariate discrimination and the Higgs + W/Z search

A systematic method for optimizing multivariate discriminants is developed and applied to the important example of a light Higgs boson search at the Tevatron and the LHC. The Significance Improvement Characteristic (SIC), defined as the signal efficiency of a cut or multivariate discriminant divided by the square root of the background efficiency, is shown to be an extremely powerful visualization tool. SIC curves demonstrate numerical instabilities in the multivariate discriminants, show convergence as the number of variables is increased, and display the sensitivity to the optimal cut values. For our application, we concentrate on Higgs boson production in association with a W or Z boson with H -> bb and compare to the irreducible standard model background, Z/W + bb. We explore thousands of experimentally motivated, physically motivated, and unmotivated single variable discriminants. Along with the standard kinematic variables, a number of new ones, such as twist, are described which should have applicability to many processes. We find that some single variables, such as the pull angle, are weak discriminants, but when combined with others they provide important marginal improvement. We also find that multiple Higgs boson-candidate mass measures, such as from mild and aggressively trimmed jets, when combined may provide additional discriminating power. Comparing the significance improvement from our variables to those used in recent CDF and DZero searches, we find that a 10-20% improvement in significance against Z/W + bb is possible. Our analysis also suggests that the H + W/Z channel with H -> bb is also viable at the LHC, without requiring a hard cut on the W/Z transverse momentum.Comment: 41 pages, 5 tables, 29 figure

Lineage divergence detected in the malaria vector Anopheles marajoara (Diptera: Culicidae) in Amazonian Brazil

<p>Abstract</p> <p>Background</p> <p>Cryptic species complexes are common among anophelines. Previous phylogenetic analysis based on the complete mtDNA <it>COI </it>gene sequences detected paraphyly in the Neotropical malaria vector <it>Anopheles marajoara</it>. The "Folmer region" detects a single taxon using a 3% divergence threshold.</p> <p>Methods</p> <p>To test the paraphyletic hypothesis and examine the utility of the Folmer region, genealogical trees based on a concatenated (<it>white </it>+ 3' <it>COI </it>sequences) dataset and pairwise differentiation of <it>COI </it>fragments were examined. The population structure and demographic history were based on partial <it>COI </it>sequences for 294 individuals from 14 localities in Amazonian Brazil. 109 individuals from 12 localities were sequenced for the nDNA <it>white </it>gene, and 57 individuals from 11 localities were sequenced for the ribosomal DNA (rDNA) internal transcribed spacer 2 (ITS2).</p> <p>Results</p> <p>Distinct <it>A. marajoara </it>lineages were detected by combined genealogical analysis and were also supported among <it>COI </it>haplotypes using a median joining network and AMOVA, with time since divergence during the Pleistocene (<100,000 ya). <it>COI </it>sequences at the 3' end were more variable, demonstrating significant pairwise differentiation (3.82%) compared to the more moderate 2.92% detected by the Folmer region. Lineage 1 was present in all localities, whereas lineage 2 was restricted mainly to the west. Mismatch distributions for both lineages were bimodal, likely due to multiple colonization events and spatial expansion (~798 - 81,045 ya). There appears to be gene flow within, not between lineages, and a partial barrier was detected near Rio Jari in Amapá state, separating western and eastern populations. In contrast, both nDNA data sets (<it>white </it>gene sequences with or without the retention of the 4th intron, and ITS2 sequences and length) detected a single <it>A. marajoara </it>lineage.</p> <p>Conclusions</p> <p>Strong support for combined data with significant differentiation detected in the <it>COI </it>and absent in the nDNA suggest that the divergence is recent, and detectable only by the faster evolving mtDNA. A within subgenus threshold of >2% may be more appropriate among sister taxa in cryptic anopheline complexes than the standard 3%. Differences in demographic history and climatic changes may have contributed to mtDNA lineage divergence in <it>A. marajoara</it>.</p

Accuracy of Malaria Rapid Diagnostic Tests in Community Studies and their Impact on Treatment of Malaria in an Area with Declining Malaria Burden in North-Eastern Tanzania.

Despite some problems related to accuracy and applicability of malaria rapid diagnostic tests (RDTs), they are currently the best option in areas with limited laboratory services for improving case management through parasitological diagnosis and reducing over-treatment. This study was conducted in areas with declining malaria burden to assess; 1) the accuracy of RDTs when used at different community settings, 2) the impact of using RDTs on anti-malarial dispensing by community-owned resource persons (CORPs) and 3) adherence of CORPs to treatment guidelines by providing treatment based on RDT results. Data were obtained from: 1) a longitudinal study of passive case detection of fevers using CORPs in six villages in Korogwe; and 2) cross-sectional surveys (CSS) in six villages of Korogwe and Muheza districts, north-eastern, Tanzania. Performance of RDTs was compared with microscopy as a gold standard, and factors affecting their accuracy were explored using a multivariate logistic regression model. Overall sensitivity and specificity of RDTs in the longitudinal study (of 23,793 febrile cases; 18,154 with microscopy and RDTs results) were 88.6% and 88.2%, respectively. In the CSS, the sensitivity was significantly lower (63.4%; χ2=367.7, p<0.001), while the specificity was significantly higher (94.3%; χ2=143.1, p<0.001) when compared to the longitudinal study. As determinants of sensitivity of RDTs in both studies, parasite density of<200 asexual parasites/μl was significantly associated with high risk of false negative RDTs (OR≥16.60, p<0.001), while the risk of false negative test was significantly lower among cases with fever (axillary temperature ≥37.5 °C) (OR≤0.63, p≤0.027). The risk of false positive RDT (as a determinant of specificity) was significantly higher in cases with fever compared to afebrile cases (OR≥2.40, p<0.001). Using RDTs reduced anti-malarials dispensing from 98.9% to 32.1% in cases aged ≥5 years. Although RDTs had low sensitivity and specificity, which varied widely depending on fever and parasite density, using RDTs reduced over-treatment with anti-malarials significantly. Thus, with declining malaria prevalence, RDTs will potentially identify majority of febrile cases with parasites and lead to improved management of malaria and non-malaria fevers

Genotype imputation for the prediction of genomic breeding values in non-genotyped and low-density genotyped individuals

<p>Abstract</p> <p>Background</p> <p>There is wide interest in calculating genomic breeding values (GEBVs) in livestock using dense, genome-wide SNP data. The general framework for genomic selection assumes all individuals are genotyped at high-density, which may not be true in practice. Methods to add additional genotypes for individuals not genotyped at high density have the potential to increase GEBV accuracy with little or no additional cost. In this study a long haplotype library was created using a long range phasing algorithm and used in combination with segregation analysis to impute dense genotypes for non-genotyped dams in the training dataset (S1) and for non-genotyped or low-density genotyped individuals in the prediction dataset (S2), using the 14^th QTL-MAS Workshop dataset. Alternative low-density scenarios were evaluated for accuracy of imputed genotypes and prediction of GEBVs.</p> <p>Results</p> <p>In S1, females in the training population were not genotyped and prediction individuals were either not genotyped or genotyped at low-density (evenly spaced at 2, 5 or 10 Mb). The proportion of correctly imputed genotypes for training females did not change when genotypes were added for individuals in the prediction set whereas the number of correctly imputed genotypes in the prediction set increased slightly (S1). The S2 scenario assumed the complete training set was genotyped for all SNPs and the prediction set was not genotyped or genotyped at low-density. The number of correctly imputed genotypes increased with genotyping density in the prediction set. Accuracy of genomic breeding values for the prediction set in each scenario were the correlation of GEBVs with true breeding values and were used to evaluate the potential loss in accuracy with reduced genotyping. For both S1 and S2 the GEBV accuracies were similar when the prediction set was not genotyped and increased with the addition of low-density genotypes, with the increase larger for S2 than S1.</p> <p>Conclusions</p> <p>Genotype imputation using a long haplotype library and segregation analysis is promising for application in sparsely-genotyped pedigrees. The results of this study suggest that dense genotypes can be imputed for selection candidates with some loss in genomic breeding value accuracy, but with levels of accuracy higher than traditional BLUP estimated breeding values. Accurate genotype imputation would allow for a single low-density SNP panel to be used across traits.</p

Generation of Three-Qubit Entangled States using Superconducting Phase Qubits

Entanglement is one of the key resources required for quantum computation, so experimentally creating and measuring entangled states is of crucial importance in the various physical implementations of a quantum computer. In superconducting qubits, two-qubit entangled states have been demonstrated and used to show violations of Bell's Inequality and to implement simple quantum algorithms. Unlike the two-qubit case, however, where all maximally-entangled two-qubit states are equivalent up to local changes of basis, three qubits can be entangled in two fundamentally different ways, typified by the states $|\mathrm{GHZ}> = (|000> + |111>)/\sqrt{2}$ and $|\mathrm{W}> = (|001> + |010> + |100>)/\sqrt{3}$. Here we demonstrate the operation of three coupled superconducting phase qubits and use them to create and measure $|\mathrm{GHZ}>$ and $|\mathrm{W}>$ states. The states are fully characterized using quantum state tomography and are shown to satisfy entanglement witnesses, confirming that they are indeed examples of three-qubit entanglement and are not separable into mixtures of two-qubit entanglement.Comment: 9 pages, 5 figures. Version 2: added supplementary information and fixed image distortion in Figure 2

Engineered 2D Ising interactions on a trapped-ion quantum simulator with hundreds of spins

The presence of long-range quantum spin correlations underlies a variety of physical phenomena in condensed matter systems, potentially including high-temperature superconductivity. However, many properties of exotic strongly correlated spin systems (e.g., spin liquids) have proved difficult to study, in part because calculations involving N-body entanglement become intractable for as few as N~30 particles. Feynman divined that a quantum simulator - a special-purpose "analog" processor built using quantum particles (qubits) - would be inherently adept at such problems. In the context of quantum magnetism, a number of experiments have demonstrated the feasibility of this approach. However, simulations of quantum magnetism allowing controlled, tunable interactions between spins localized on 2D and 3D lattices of more than a few 10's of qubits have yet to be demonstrated, owing in part to the technical challenge of realizing large-scale qubit arrays. Here we demonstrate a variable-range Ising-type spin-spin interaction J_ij on a naturally occurring 2D triangular crystal lattice of hundreds of spin-1/2 particles (9Be+ ions stored in a Penning trap), a computationally relevant scale more than an order of magnitude larger than existing experiments. We show that a spin-dependent optical dipole force can produce an antiferromagnetic interaction J_ij ~ 1/d_ij^a, where a is tunable over 0<a<3; d_ij is the distance between spin pairs. These power-laws correspond physically to infinite-range (a=0), Coulomb-like (a=1), monopole-dipole (a=2) and dipole-dipole (a=3) couplings. Experimentally, we demonstrate excellent agreement with theory for 0.05<a<1.4. This demonstration coupled with the high spin-count, excellent quantum control and low technical complexity of the Penning trap brings within reach simulation of interesting and otherwise computationally intractable problems in quantum magnetism.Comment: 10 pages, 10 figures; article plus Supplementary Material

Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations

The tomato Prf complex is a molecular trap for bacterial effectors based on Pto transphosphorylation

The bacteria Pseudomonas syringae is a pathogen of many crop species and one of the model pathogens for studying plant and bacterial arms race coevolution. In the current model, plants perceive bacteria pathogens via plasma membrane receptors, and recognition leads to the activation of general defenses. In turn, bacteria inject proteins called effectors into the plant cell to prevent the activation of immune responses. AvrPto and AvrPtoB are two such proteins that inhibit multiple plant kinases. The tomato plant has reacted to these effectors by the evolution of a cytoplasmic resistance complex. This complex is compromised of two proteins, Prf and Pto kinase, and is capable of recognizing the effector proteins. How the Pto kinase is able to avoid inhibition by the effector proteins is currently unknown. Our data shows how the tomato plant utilizes dimerization of resistance proteins to gain advantage over the faster evolving bacterial pathogen. Here we illustrate that oligomerisation of Prf brings into proximity two Pto kinases allowing them to avoid inhibition by the effectors by transphosphorylation and to activate immune responses