Spatial coherence of forward-scattered light in a turbid medium

We study spatially coherent forward-scattered light propagating in a turbid medium of moderate optical depth (0-9 mean free paths). Coherent detection was achieved by using a tilted heterodyne geometry, which desensitizes coherent detection of the attenuated incident light. We show that the degree of spatial coherence is significantly higher for light scattered only once in comparison with that for multiply scattered light and that it approaches a small constant value for large numbers of scattering events

Interactions between Plasmodium falciparum skeleton-binding protein 1 and the membrane skeleton of malaria-infected red blood cells

During development inside red blood cells (RBCs), Plasmodium falciparum malaria parasites export proteins that associate with the RBC membrane skeleton. These interactions cause profound changes to the biophysical properties of RBCs that underpin the often severe and fatal clinical manifestations of falciparum malaria. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is one such exported parasite protein that plays a major role in malaria pathogenesis since its exposure on the parasitised RBC surface mediates their adhesion to vascular endothelium and placental syncytioblasts. En route to the RBC membrane skeleton, PfEMP1 transiently associates with Maurer\u27s clefts (MCs), parasite-derived membranous structures in the RBC cytoplasm. We have previously shown that a resident MC protein, skeleton-binding protein 1 (SBP1), is essential for the placement of PfEMP1 onto the RBC surface and hypothesised that the function of SBP1 may be to target MCs to the RBC membrane. Since this would require additional protein interactions, we set out to identify binding partners for SBP1. Using a combination of approaches, we have defined the region of SBP1 that binds specifically to defined sub-domains of two major components of the RBC membrane skeleton, protein 4.1R and spectrin. We show that these interactions serve as one mechanism to anchor MCs to the RBC membrane skeleton, however, while they appear to be necessary, they are not sufficient for the translocation of PfEMP1 onto the RBC surface. The N-terminal domain of SBP1 that resides within the lumen of MCs clearly plays an essential, but presently unknown role in this process

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

Heat shock factor-1 modulates p53 activity in the transcriptional response to DNA damage

Here we define an important role for heat shock factor 1 (HSF1) in the cellular response to genotoxic agents. We demonstrate for the first time that HSF1 can complex with nuclear p53 and that both proteins are co-operatively recruited to p53-responsive genes such as p21. Analysis of natural and synthetic cis elements demonstrates that HSF1 can enhance p53-mediated transcription, whilst depletion of HSF1 reduces the expression of p53-responsive transcripts. We find that HSF1 is required for optimal p21 expression and p53-mediated cell-cycle arrest in response to genotoxins while loss of HSF1 attenuates apoptosis in response to these agents. To explain these novel properties of HSF1 we show that HSF1 can complex with DNA damage kinases ATR and Chk1 to effect p53 phosphorylation in response to DNA damage. Our data reveal HSF1 as a key transcriptional regulator in response to genotoxic compounds widely used in the clinical setting, and suggest that HSF1 will contribute to the efficacy of these agents

Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector

A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino

Glycans in Sera of Amyotrophic Lateral Sclerosis Patients and Their Role in Killing Neuronal Cells

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by degeneration of upper and lower motor neurons. To date, glycosylation patterns of glycoproteins in fluids of ALS patients have not been described. Moreover, the aberrant glycosylation related to the pathogenesis of other neurodegenerative diseases encouraged us to explore the glycome of ALS patient sera. We found high levels of sialylated glycans and low levels of core fucosylated glycans in serum-derived N-glycans of patients with ALS, compared to healthy volunteer sera. Based on these results, we analyzed the IgG Fc N297-glycans, as IgG are major serum glycoproteins affected by sialylation or core fucosylation and are found in the motor cortex of ALS patients. The analyses revealed a distinct glycan, A2BG2, in IgG derived from ALS patient sera (ALS-IgG). This glycan increases the affinity of IgG to CD16 on effector cells, consequently enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC). Therefore, we explore whether the Fc-N297-glycans of IgG may be involved in ALS disease. Immunostaining of brain and spinal cord tissues revealed over-expression of CD16 and co-localization of intact ALS-IgG with CD16 and in brain with activated microglia of G93A-SOD1 mice. Intact ALS-IgG enhanced effector cell activation and ADCC reaction in comparison to sugar-depleted or control IgG. ALS-IgG were localized in the synapse between brain microglia and neurons of G93A-SOD1 mice, manifesting a promising in vivo ADCC reaction. Therefore, glycans of ALS-IgG may serve as a biomarker for the disease and may be involved in neuronal damage

Advances in estimation by the item sum technique using auxiliary information in complex surveys

To collect sensitive data, survey statisticians have designed many strategies to reduce nonresponse rates and social desirability response bias. In recent years, the item count technique (ICT) has gained considerable popularity and credibility as an alternative mode of indirect questioning survey, and several variants of this technique have been proposed as new needs and challenges arise. The item sum technique (IST), which was introduced by Chaudhuri and Christofides (2013) and Trappmann et al. (2014), is one such variant, used to estimate the mean of a sensitive quantitative variable. In this approach, sampled units are asked to respond to a two-list of items containing a sensitive question related to the study variable and various innocuous, nonsensitive, questions. To the best of our knowledge, very few theoretical and applied papers have addressed the IST. In this article, therefore, we present certain methodological advances as a contribution to appraising the use of the IST in real-world surveys. In particular, we employ a generic sampling design to examine the problem of how to improve the estimates of the sensitive mean when auxiliary information on the population under study is available and is used at the design and estimation stages. A Horvitz-Thompson type estimator and a calibration type estimator are proposed and their efficiency is evaluated by means of an extensive simulation study. Using simulation experiments, we show that estimates obtained by the IST are nearly equivalent to those obtained using “true data” and that in general they outperform the estimates provided by a competitive randomized response method. Moreover, the variance estimation may be considered satisfactory. These results open up new perspectives for academics, researchers and survey practitioners, and could justify the use of the IST as a valid alternative to traditional direct questioning survey modes.Ministerio de Economía y Competitividad of SpainMinisterio de Educacion, Cultura y Deporteproject PRIN-SURWE

An Updated Review of Tyrosinase Inhibitors

Tyrosinase is a multifunctional, glycosylated, and copper-containing oxidase, which catalyzes the first two steps in mammalian melanogenesis and is responsible for enzymatic browning reactions in damaged fruits during post-harvest handling and processing. Neither hyperpigmentation in human skin nor enzymatic browning in fruits are desirable. These phenomena have encouraged researchers to seek new potent tyrosinase inhibitors for use in foods and cosmetics. This article surveys tyrosinase inhibitors newly discovered from natural and synthetic sources. The inhibitory strength is compared with that of a standard inhibitor, kojic acid, and their inhibitory mechanisms are discussed

The Liver Tumor Segmentation Benchmark (LiTS)

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LITS) organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2016 and International Conference On Medical Image Computing Computer Assisted Intervention (MICCAI) 2017. Twenty four valid state-of-the-art liver and liver tumor segmentation algorithms were applied to a set of 131 computed tomography (CT) volumes with different types of tumor contrast levels (hyper-/hypo-intense), abnormalities in tissues (metastasectomie) size and varying amount of lesions. The submitted algorithms have been tested on 70 undisclosed volumes. The dataset is created in collaboration with seven hospitals and research institutions and manually reviewed by independent three radiologists. We found that not a single algorithm performed best for liver and tumors. The best liver segmentation algorithm achieved a Dice score of 0.96(MICCAI) whereas for tumor segmentation the best algorithm evaluated at 0.67(ISBI) and 0.70(MICCAI). The LITS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.Comment: conferenc