Granular discharge and clogging for tilted hoppers

We measure the flux of spherical glass beads through a hole as a systematic function of both tilt angle and hole diameter, for two different size beads. The discharge increases with hole diameter in accord with the Beverloo relation for both horizontal and vertical holes, but in the latter case with a larger small-hole cutoff. For large holes the flux decreases linearly in cosine of the tilt angle, vanishing smoothly somewhat below the angle of repose. For small holes it vanishes abruptly at a smaller angle. The conditions for zero flux are discussed in the context of a {\it clogging phase diagram} of flow state vs tilt angle and ratio of hole to grain size

Mitochondrial carrier homolog 1 (Mtch1) antibodies in neuro-Behçet's disease

Cataloged from PDF version of article.Efforts for the identification of diagnostic autoantibodies for neuro-Behcet's disease (NBD) have failed. Screening of NBD patients' sera with protein macroarray identified mitochondrial carrier homolog 1 (Mtch1), an apoptosis-related protein, as a potential autoantigen. ELISA studies showed serum Mtch1 antibodies in 68 of 144 BD patients with or without neurological involvement and in 4 of 168 controls corresponding to a sensitivity of 47.2% and specificity of 97.6%. Mtch1 antibody positive NBD patients had more attacks, increased disability and lower serum nucleosome levels. Mtch1 antibody might be involved in pathogenic mechanisms of NBD rather than being a coincidental byproduct of autoinflammation. © 2013 Elsevier B.V

Dissipation and fluctuations in nanoelectromechanical systems based on carbon nanotubes

Tribological characteristics of nanotube-based nanoelectromechanical systems (NEMS) exemplified by a gigahertz oscillator are studied. Various factors that influence the tribological properties of the nanotube-based NEMS are quantitatively analyzed with the use of molecular dynamics calculations of the quality factor (Q-factor) of the gigahertz oscillator. We demonstrate that commensurability of the nanotube walls can increase the dissipation rate, while the structure of the wall ends and the nanotube length do not influence the Q-factor. It is shown that the dissipation rate depends on the interwall distance and the way of fixation of the outer wall and is significant in the case of a poor fixation for the nanotubes with a large interwall distance. Defects are found to strongly decrease the Q-factor due to the excitation of low-frequency vibrational modes. No universal correlation between the static friction forces and the energy dissipation rate is established. We propose an explanation of the obtained results on the basis of the classical theory of vibrational-translational relaxation. Significant thermodynamics fluctuations are revealed in the gigahertz oscillator by molecular dynamics simulations and analyzed in the framework of the fluctuation-dissipation theorem. Possibility of designing the NEMS with a desirable Q-factor and their applications are discussed on the basis of the above results.Comment: 32 pages, 7 figure

Drug-resistant genotypes and multi-clonality in Plasmodium falciparum analysed by direct genome sequencing from peripheral blood of malaria patients.

Naturally acquired blood-stage infections of the malaria parasite Plasmodium falciparum typically harbour multiple haploid clones. The apparent number of clones observed in any single infection depends on the diversity of the polymorphic markers used for the analysis, and the relative abundance of rare clones, which frequently fail to be detected among PCR products derived from numerically dominant clones. However, minority clones are of clinical interest as they may harbour genes conferring drug resistance, leading to enhanced survival after treatment and the possibility of subsequent therapeutic failure. We deployed new generation sequencing to derive genome data for five non-propagated parasite isolates taken directly from 4 different patients treated for clinical malaria in a UK hospital. Analysis of depth of coverage and length of sequence intervals between paired reads identified both previously described and novel gene deletions and amplifications. Full-length sequence data was extracted for 6 loci considered to be under selection by antimalarial drugs, and both known and previously unknown amino acid substitutions were identified. Full mitochondrial genomes were extracted from the sequencing data for each isolate, and these are compared against a panel of polymorphic sites derived from published or unpublished but publicly available data. Finally, genome-wide analysis of clone multiplicity was performed, and the number of infecting parasite clones estimated for each isolate. Each patient harboured at least 3 clones of P. falciparum by this analysis, consistent with results obtained with conventional PCR analysis of polymorphic merozoite antigen loci. We conclude that genome sequencing of peripheral blood P. falciparum taken directly from malaria patients provides high quality data useful for drug resistance studies, genomic structural analyses and population genetics, and also robustly represents clonal multiplicity

ESTIMATING GENOME-WIDE COPY NUMBER USING ALLELE SPECIFIC MIXTURE MODELS

Genomic changes such as copy number alterations are thought to be one of the major underlying causes of human phenotypic variation among normal and disease subjects [23,11,25,26,5,4,7,18]. These include chromosomal regions with so-called copy number alterations: instead of the expected two copies, a section of the chromosome for a particular individual may have zero copies (homozygous deletion), one copy (hemizygous deletions), or more than two copies (amplifications). The canonical example is Down syndrome which is caused by an extra copy of chromosome 21. Identification of such abnormalities in smaller regions has been of great interest, because it is believed to be an underlying cause of cancer. More than one decade ago comparative genomic hybridization (CGH)technology was developed to detect copy number changes in a high-throughput fashion. However, this technology only provides a 10 MB resolution which limits the ability to detect copy number alterations spanning small regions. It is widely believed that a copy number alteration as small as one base can have significant downstream effects, thus microarray manufacturers have developed technologies that provide much higher resolution. Unfortunately, strong probe effects and variation introduced by sample preparation procedures have made single-point copy number estimates too imprecise to be useful. CGH arrays use a two-color hybridization, usually comparing a sample of interest to a reference sample, which to some degree removes the probe effect. However, the resolution is not nearly high enough to provide single-point copy number estimates. Various groups have proposed statistical procedures that pool data from neighboring locations to successfully improve precision. However, these procedure need to average across relatively large regions to work effectively thus greatly reducing the resolution. Recently, regression-type models that account for probe-effect have been proposed and appear to improve accuracy as well as precision. In this paper, we propose a mixture model solution specifically designed for single-point estimation, that provides various advantages over the existing methodology. We use a 314 sample database, constructed with public datasets, to motivate and fit models for the conditional distribution of the observed intensities given allele specific copy numbers. With the estimated models in place we can compute posterior probabilities that provide a useful prediction rule as well as a confidence measure for each call. Software to implement this procedure will be available in the Bioconductor oligo packagehttp://www.bioconductor.org)

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine: Brussels, Belgium. 15-18 March 2016.

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Strategic and operational decision-making in expanding supply chains for LNG as a fuel

The European Union aims for a 40% reduction in greenhouse gas emissions by 2030, compared to 1990 levels, and recognizes the opportunities of Liquefied Natural Gas (LNG) as an alternative fuel for transportation to reach this goal. The lack of a mature supply chain for LNG as a fuel results in a need to invest in new (satellite) terminals, bunker barges and tanker trucks. This network design problem can be defined as a Two-Echelon Capacitated Location Routing Problem with Split Deliveries (2E-CLRPSP). An important feature of this problem is that direct deliveries are allowed from terminals, which makes the problem much harder to solve than the existing location routing literature suggests. In this paper, we improve the performance of a hybrid exact algorithm and apply our algorithm to a real world network design problem related to the expansion of the European supply chain for LNG as a fuel. We show that satellite terminals and bunker barges become an interesting option when demand for LNG grows and occurs further away from the import terminal. In those situations, the large investments associated with LNG satellites and bunker barges are offset by reductions in operational costs of the LNG tanker trucks

Consistency-based detection of potential tumor-specific deletions in matched normal/tumor genomes

Wittler R, Chauve C. Consistency-based detection of potential tumor-specific deletions in matched normal/tumor genomes. BMC Bioinformatics. 2011;12(Suppl. 9):S21

Enhanced genetic maps from family-based disease studies: population-specific comparisons

Abstract Background Accurate genetic maps are required for successful and efficient linkage mapping of disease genes. However, most available genome-wide genetic maps were built using only small collections of pedigrees, and therefore have large sampling errors. A large set of genetic studies genotyped by the NHLBI Mammalian Genotyping Service (MGS) provide appropriate data for generating more accurate maps. Results We collected a large sample of uncleaned genotype data for 461 markers generated by the MGS using the Weber screening sets 9 and 10. This collection includes genotypes for over 4,400 pedigrees containing over 17,000 genotyped individuals from different populations. We identified and cleaned numerous relationship and genotyping errors, as well as verified the marker orders. We used this dataset to test for population-specific genetic maps, and to re-estimate the genetic map distances with greater precision; standard errors for all intervals are provided. The map-interval sizes from the European (or European descent), Chinese, and Hispanic samples are in quite good agreement with each other. We found one map interval on chromosome 8p with a statistically significant size difference between the European and Chinese samples, and several map intervals with significant size differences between the African American and Chinese samples. When comparing Palauan with European samples, a statistically significant difference was detected at the telomeric region of chromosome 11p. Several significant differences were also identified between populations in chromosomal and genome lengths. Conclusions Our new population-specific screening set maps can be used to improve the accuracy of disease-mapping studies. As a result of the large sample size, the average length of the 95% confidence interval (CI) for a 10 cM map interval is only 2.4 cM, which is considerably smaller than on previously published maps.http://deepblue.lib.umich.edu/bitstream/2027.42/112826/1/12881_2010_Article_748.pd

Novel formulations of oral bisphosphonates in the treatment of osteoporosis.

Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still maintaining the efficacy of fracture risk reduction. Clinical trials and real-world data have been employed to demonstrate some benefits in terms of reduced upper gastro-intestinal adverse events, adherence, persistence and health economic outcomes. This report describes the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores where oral bisphosphonates sit in current clinical practice guidelines, review their risk-benefit profile and the consequences of poor adherence before exploring novel oral bisphosphonate formulations and their potential clinical and health economic impact. Further research is required but there are signs that these novel, oral bisphosphonate formulations may lead to improved tolerance of oral bisphosphonates and thus, improved adherence and fracture outcomes