Random walks and market efficiency in Chinese and Indian equity markets

Hypothesis of Market Efficiency is an important concept for the investors across the globe holding diversified portfolios. With the world economy getting more integrated day by day, more people are investing in global emerging markets. This means that it is pertinent to understand the efficiency of these markets. This paper tests for market efficiency by studying the impact of global financial crisis of 2008 and the recent Chinese crisis of 2015 on stock market efficiency in emerging stock markets of China and India. The data for last 20 years was collected from both Bombay Stock Exchange (BSE200) and the Shanghai Stock Exchange Composite Index and divided into four sub-periods, i.e. before financial crisis period (period-I), during recession (period-II), after recession and before Chinese Crisis (periodIII) and from the start of Chinese crisis till date (period- IV). Daily returns for the SSE and BSE were examined and tested for randomness using a combination of auto correlation tests, runs tests and unit root tests (Augmented Dickey-Fuller) for the entire sample period and the four sub-periods. The evidence from all these tests supports that both the Indian and Chinese stock markets do not exhibit weak form of market efficiency. They do not follow random walk overall and in the first three periods (1996 till the 2015) implying that recession did not impact the markets to a great extent, although the efficiency in percentage terms seems to be increasing after the global financial crisis of 2008

P38 and JNK have opposing effects on persistence of in vivo leukocyte migration in zebrafish

The recruitment and migration of macrophages and neutrophils is an important process during the early stages of the innate immune system in response to acute injury. Transgenic pu.1:EGFP zebrafish permit the acquisition of leukocyte migration trajectories during inflammation. Currently, these high-quality live-imaging data are mainly analysed using general statistics, for example, cell velocity. Here, we present a spatio-temporal analysis of the cell dynamics using transition matrices, which provide information of the type of cell migration. We find evidence that leukocytes exhibit types of migratory behaviour, which differ from previously described random walk processes. Dimethyl sulfoxide treatment decreased the level of persistence at early time points after wounding and ablated temporal dependencies observed in untreated embryos. We then use pharmacological inhibition of p38 and c-Jun N-terminal kinase mitogen-activated protein kinases to determine their effects on in vivo leukocyte migration patterns and discuss how they modify the characteristics of the cell migration process. In particular, we find that their respective inhibition leads to decreased and increased levels of persistent motion in leukocytes following wounding. This example shows the high level of information content, which can be gained from live-imaging data if appropriate statistical tools are used

Induction of innate cytokine responses by respiratory mucosal challenge with R848 in zebrafish, mice, and humans.

We compared live zebrafish, mouse and human nasal challenge responses to the TLR7/8 agonist resiquimod (R848). We found remarkably similar induction of mediators in the three species, offering novel mucosal models of innate anti-viral immunity

Notch ligation by Delta1 inhibits peripheral immune responses to transplantation antigens by a CD8⁺ cell–dependent mechanism

Notch signaling plays a fundamental role in determining the outcome of differentiation processes in many tissues. Notch signaling has been implicated in T versus B cell lineage commitment, thymic differentiation, and bone marrow hematopoietic precursor renewal and differentiation. Notch receptors and their ligands are also expressed on the surface of mature lymphocytes and APCs, but the effects of Notch signaling in the peripheral immune system remain poorly defined. The aim of the studies reported here was to investigate the effects of signaling through the Notch receptor using a ligand of the Delta-like family. We show that Notch ligation in the mature immune system markedly decreases responses to transplantation antigens. Constitutive expression of Delta-like 1 on alloantigen-bearing cells renders them nonimmunogenic and able to induce specific unresponsiveness to a challenge with the same alloantigen, even in the form of a cardiac allograft. These effects could be reversed by depletion of CD8⁺ cells at the time of transplantation. Ligation of Notch on splenic CD8⁺ cells results in a dramatic decrease in IFN-γ with a concomitant enhancement of IL-10 production, suggesting that Notch signaling can alter the differentiation potential of CD8⁺ cells. These data implicate Notch signaling in regulation of peripheral immunity and suggest a novel approach for manipulating deleterious immune responses

MMBGX: a method for estimating expression at the isoform level and detecting differential splicing using whole-transcript Affymetrix arrays

Affymetrix has recently developed whole-transcript GeneChips—‘Gene’ and ‘Exon’ arrays—which interrogate exons along the length of each gene. Although each probe on these arrays is intended to hybridize perfectly to only one transcriptional target, many probes match multiple transcripts located in different parts of the genome or alternative isoforms of the same gene. Existing statistical methods for estimating expression do not take this into account and are thus prone to producing inflated estimates. We propose a method, Multi-Mapping Bayesian Gene eXpression (MMBGX), which disaggregates the signal at ‘multi-match’ probes. When applied to Gene arrays, MMBGX removes the upward bias of gene-level expression estimates. When applied to Exon arrays, it can further disaggregate the signal between alternative transcripts of the same gene, providing expression estimates of individual splice variants. We demonstrate the performance of MMBGX on simulated data and a tissue mixture data set. We then show that MMBGX can estimate the expression of alternative isoforms within one experimental condition, confirming our results by RT-PCR. Finally, we show that our method for detecting differential splicing has a lower error rate than standard exon-level approaches on a previously validated colon cancer data set

Modular Synthesis of Semiconducting Graft Co-polymers to Achieve "clickable" Fluorescent Nanoparticles with Long Circulation and Specific Cancer Targeting

Semiconducting polymer nanoparticles (SPNs) have been explored for applications in cancer theranostics because of their high absorption coefficients, photostability and biocompatibility. However, SPNs are susceptible to aggregation and protein fouling in physiological conditions, which can be detrimental for in vivo applications. Here, we describe a method for achieving colloidally stable and low-fouling SPNs by grafting PEG onto the backbone of the fluorescent semiconducting polymer, poly(9,9'-dioctylfluorene-5-fluoro-2,1,3-benzothiadiazole) (F8BT-F), in a simple one-step substitution reaction, post-polymerisation. Further, by utilising azide-functionalised PEG we site-specifically "click" anti-HER2 antibodies, Fab fragments, or affibodies onto the SPN surface, which allows the functionalised SPNs to specifically target HER2-positive cancer cells. In vivo, our PEGylated SPNs were found to have excellent circulation efficiencies in zebrafish embryos for up to seven days post-injection. SPNs functionalised with affibodies were then shown to be able to target HER2 expressing cancer cells in a zebrafish xenograft model. The covalent PEGylated SPN system described herein shows great potential for cancer theranostics. This article is protected by copyright. All rights reserved

FLIM FRET Technology for Drug Discovery: Automated Multiwell-Plate High-Content Analysis, Multiplexed Readouts and Application in Situ**

A fluorescence lifetime imaging (FLIM) technology platform intended to read out changes in Förster resonance energy transfer (FRET) efficiency is presented for the study of protein interactions across the drug-discovery pipeline. FLIM provides a robust, inherently ratiometric imaging modality for drug discovery that could allow the same sensor constructs to be translated from automated cell-based assays through small transparent organisms such as zebrafish to mammals. To this end, an automated FLIM multiwell-plate reader is described for high content analysis of fixed and live cells, tomographic FLIM in zebrafish and FLIM FRET of live cells via confocal endomicroscopy. For cell-based assays, an exemplar application reading out protein aggregation using FLIM FRET is presented, and the potential for multiple simultaneous FLIM (FRET) readouts in microscopy is illustrated

Trends and patterns in antibiotic prescribing among out-of-hours primary care providers in England, 2010–14

Objectives: Antimicrobial resistance is a global threat, increasing morbidity and mortality. In England, publicly funded clinical commissioning groups (CCGs) commission out-of-hours (OOH) primary care services outside daytime hours. OOH consultations represent 1% of in-hours general practice (GP) consultations. Antibiotic prescriptions increased 32% in non-GP community services between 2010 and 2013. We describe OOH antibiotic prescribing patterns and trends between 2010 and 2014. Methods: We: estimated the proportion of CCGs with OOH data available; described and compared antibiotic prescribing by volume of prescribed items, seasonality and trends in GP and OOH, using linear regression; and compared the proportion of broad-spectrum to total antibiotic prescriptions in OOHs with their respective CCGs in terms of seasonality and trends, using binomial regression. Results: Data were available for 143 of 211 (68%) CCGs. OOH antibiotic prescription volume represented 4.5%-5.4% of GP prescription volume and was stable over time ( P  =   0.37). The proportion of broad-spectrum antibiotic prescriptions increased in OOH when it increased in the CCG they operated in (regression coefficient 0.98; 95% CI 0.96-0.99). Compared with GP, the proportion of broad-spectrum antibiotic prescriptions in OOH was higher but decreased both in GP and OOH (-0.57%, 95% CI - 0.54% to - 0.6% and -0.76%, 95% CI - 0.59% to - 0.93% per year, respectively). Conclusions: OOH proportionally prescribed more antibiotics than GPs although we could not comment on prescribing appropriateness. OOH prescribing volume was stable over time, and followed GP seasonal patterns. OOH antibiotic prescribing reflected the CCGs they operated in but with relatively more broad-spectrum antibiotics than in-hours GP. Understanding factors influencing prescribing in OOH will enable the development of tailored interventions promoting optimal prescribing in this setting

REPORT Whole-Exome Sequencing Links a Variant in DHDDS to Retinitis Pigmentosa

Increasingly, mutations in genes causing Mendelian disease will be supported by individual and small families only; however, exome sequencing studies have thus far focused on syndromic phenotypes characterized by low locus heterogeneity. In contrast, retinitis pigmentosa (RP) is caused by >50 known genes, which still explain only half of the clinical cases. In a single, one-generation, nonsyndromic RP family, we have identified a gene, dehydrodolichol diphosphate synthase (DHDDS), demonstrating the power of combining whole-exome sequencing with rapid in vivo studies. DHDDS is a highly conserved essential enzyme for dolichol synthesis, permitting global N-linked glycosylation. Zebrafish studies showed virtually identical photoreceptor defects as observed with N-linked glycosylation-interfering mutations in the light-sensing protein rhodopsin. The identified Lys42Glu variant likely arose from an ancestral founder, because eight of the nine identified alleles in 27,174 control chromosomes were of confirmed Ashkenazi Jewish ethnicity. These findings demonstrate the power of exome sequencing linked to functional studies when faced with challenging study designs and, importantly, link RP to the pathways of N-linked glycosylation, which promise new avenues for therapeutic interventions. Retinitis pigmentosa (RP) refers to a large group of genetically heterogeneous retinal degenerative disorders characterized by early rod photoreceptor dysfunction followed by progressive rod and cone photoreceptor dysfunction and photoreceptor death (MIM 268000). Impaired night vision followed by impaired peripheral vision generally starts in adolescence to young adulthood, with subsequent impaired central vision in later life. We studied a family of Ashkenazi Jewish (AJ) origin in which three out of four siblings (two females and one male) were diagnosed with RP in their teenage years ( To identify the genetic cause of this likely recessive subtype of RP, we screened all genes known to harbor RP mutations and found that they were negative for mutations. Classic linkage approaches were not applicable because of the size of the nonconsanguineous family, so we performed whole-exome sequencing in the three affected siblings and one unaffected sibling (Whole Human Exome Capture kit, Roche). We produced approximately 10 gigabases (Gb) of paired-end 75 bp sequence reads per individual on the Illumina GAII platform. To test the overall quality of the sequence data, we compared the genotypes of variants found in the sequence data to variants derived from genotyping via a genome-wide SN