The flash crash: The impact of high frequency trading on an electronic market

The Flash Crash, a brief period of extreme market volatility on May 6, 2010, raised questions about the current structure of the U.S. financial markets. We use audit-trail data to describe the structure of the E-mini S&P 500 stock index futures market on May 6. We ask three questions. How did High Frequency Traders (HFTs) trade on May 6? What may have triggered the Flash Crash? What role did HFTs play in the Flash Crash? We conclude that HFTs did not trigger the Flash Crash, but their responses to the unusually large selling pressure on that day exacerbated market volatility

Size Segregation of Granular Matter in Silo Discharges

We present an experimental study of segregation of granular matter in a quasi-two dimensional silo emptying out of an orifice. Size separation is observed when multi-sized particles are used with the larger particles found in the center of the silo in the region of fastest flow. We use imaging to study the flow inside the silo and quantitatively measure the concentration profiles of bi-disperse beads as a function of position and time. The angle of the surface is given by the angle of repose of the particles, and the flow occurs in a few layers only near the top of this inclined surface. The flowing region becomes deeper near the center of the silo and is confined to a parabolic region centered at the orifice which is approximately described by the kinematic model. The experimental evidence suggests that the segregation occurs on the surface and not in the flow deep inside the silo where velocity gradients also are present. We report the time development of the concentrations of the bi-disperse particles as a function of size ratios, flow rate, and the ratio of initial mixture. The qualitative aspects of the observed phenomena may be explained by a void filling model of segregation.Comment: 6 pages, 10 figures (gif format), postscript version at http://physics.clarku.edu/~akudrolli/nls.htm

Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tThis is an open access article available at http://www.eje-online.org/content/172/6/697.BACKGROUND: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey. DESIGN AND METHODS: NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed. RESULTS: Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8 (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births. CONCLUSIONS: Homozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort.The genetic testing was funded by the Wellcome Trust (Senior Investigator Award to Profs S Ellard and A T Hattersley), and by Diabetes UK (Project funding to Dr D J Mackay). H Demirbilek was funded by European Society for Paediatric Endocrinology (ESPE) and The Scientific and Technological Research Council of Turkey (TUBITAK) for his 1 year clinical fellowship at University College London (UCL), Institute of Child Health, Great Ormond Street Hospital for Children, NHS Trust, Department of Paediatric Endocrinology

Non-alignment comparison of human and high primate genomes

Compositional spectra (CS) analysis based on k-mer scoring of DNA sequences was employed in this study for dot-plot comparison of human and primate genomes. The detection of extended conserved synteny regions was based on continuous fuzzy similarity rather than on chains of discrete anchors (genes or highly conserved noncoding elements). In addition to the high correspondence found in the comparisons of whole-genome sequences, a good similarity was also found after masking gene sequences, indicating that CS analysis manages to reveal phylogenetic signal in the organization of noncoding part of the genome sequences, including repetitive DNA and the genome "dark matter". Obviously, the possibility to reveal parallel ordering depends on the signal of common ancestor sequence organization varying locally along the corresponding segments of the compared genomes. We explored two sources contributing to this signal: sequence composition (GC content) and sequence organization (abundances of k-mers in the usual A,T,G,C or purine-pyrimidine alphabets). Whole-genome comparisons based on GC distribution along the analyzed sequences indeed gives reasonable results, but combining it with k-mer abundances dramatically improves the ordering quality, indicating that compositional and organizational heterogeneity comprise complementary sources of information on evolutionary conserved similarity of genome sequences

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

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

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.]