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Mapping minimum reflection distribution of surface plasmon resonance with a complex refractive index
One of the main challenges in making any further advances in the field of SPR biosensing is in the detection of small molecules, low analyte concentrations, and single particle interactions. To this end, labels have been used to amplify the signal of this traditional label-free technique. The physical properties associated with these labels can enhance the SPR signal by affecting the dielectric constant both in the real and imaginary parts. In this paper, we have taken a holistic approach to considering the dielectric properties of these labels and their effect on the minimum resonance intensity (MI) is mapped for the Kretschmann SPR configuration. These maps provide a way for matching label properties for particular SPR conditions and reveal that thicker Au films (âŒ65 nm) make the MI method more suitable for the detection of absorbing materials. Whereas the wavelength SPR at 50 nm Au film thickness generates a shift of similar or lower magnitude for adsorption of the absorbing label, compared with BSA adsorption, in the 'thick'-film SPR using the MI format, the signal due to the non-absorbing BSA adsorption tends towards zero (background), whereas the absorbing label produces a large well resolved signal.This research is supported by National Natural Science Foundation of China (NSFC, 31271064), International Exchanges Scheme 2012 China Costshare between Royal Society, UK and NSFC (31311130124), and Fundamental Research Funds for the central University
Pooled analysis of TNF inhibitor biosimilar studies comparing radiographic progression by disease activity states in rheumatoid arthritis
Objective: To evaluate the relationship between disease activity and radiographic progression in rheumatoid arthritis, three phase III studies of SB4, SB2 and SB5 (biosimilars of etanercept, infliximab and adalimumab) were pooled to assess radiographic progression by disease activity status.
Methods: Patients from each study with radiographic data were pooled and grouped based on disease activity state (remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA)), determined by disease activity score based on 28-joint count (DAS28) per erythrocyte sedimentation rate, Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) at different time points. Mean change in modified Total Sharp Score (mTSS) and the proportion of radiographic non-progressors of higher disease activity groups (LDA, MDA and HDA) in reference to remission were summarised descriptively, with comparison of ORs using logistic models.
Results: 1265 patients were included. In all treatments combined, the 1âyear mean change in mTSS was 0.03, 0.4, 0.3 and 1.3 and proportion of radiographic non-progressors was 79.8%, 78.1%, 74.1% and 58.4% in the week 24/30 DAS28-determined remission, LDA, MDA and HDA groups, respectively. ORs (95% CIs) of the proportion of non-progressors were lowest in the HDA group in reference to remission (0.35 (0.23 to 0.54)), followed by MDA (0.72 (0.50 to 1.05)) and LDA (0.90 (0.55 to 1.48)) groups. Similar trends were observed when disease activity was assessed using SDAI or CDAI.
Conclusion: A pooled analysis of radiographic assessment data from three biosimilar studies showed that radiographic progression is small overall but increases with worse disease activity.
Trial registration numbers: NCT01895309, NCT01936181 and NCT0216713
Quantum interferometry with three-dimensional geometry
Quantum interferometry uses quantum resources to improve phase estimation
with respect to classical methods. Here we propose and theoretically
investigate a new quantum interferometric scheme based on three-dimensional
waveguide devices. These can be implemented by femtosecond laser waveguide
writing, recently adopted for quantum applications. In particular, multiarm
interferometers include "tritter" and "quarter" as basic elements,
corresponding to the generalization of a beam splitter to a 3- and 4-port
splitter, respectively. By injecting Fock states in the input ports of such
interferometers, fringe patterns characterized by nonclassical visibilities are
expected. This enables outperforming the quantum Fisher information obtained
with classical fields in phase estimation. We also discuss the possibility of
achieving the simultaneous estimation of more than one optical phase. This
approach is expected to open new perspectives to quantum enhanced sensing and
metrology performed in integrated photonic.Comment: 7 pages (+4 Supplementary Information), 5 figure
Band-gap expansion in the surface-localized electronic structure of MoS2(0002)
The electronic band structure of MoS2 single crystals has been investigated using angle-resolved photoelectron spectroscopy and first-principles calculations. The orbital symmetry and k dispersion of these electronic states responsible for the direct and the indirect electronic band gaps have been unambiguously determined. By experimentally probing an increase of the electronic band gap, we conclude that a MoS2 (0002) surface localized state exists just below the valence band maximum at the Gamma point. This electronic state originates from the sulfur planes within the topmost layer. Our comprehensive study addresses the surface electronic structure of MoS2 and the role of van der Waals interlayer interactions.open112625Nsciescopu
Physical parameters affecting sonoluminescence: A self-consistent hydrodynamic study
We studied the dependence of thermodynamic variables in a sonoluminescing ~SL! bubble on various physical factors, which include viscosity, thermal conductivity, surface tension, the equation of state of the gas inside the bubble, as well as the compressibility of the surrounding liquid. The numerical solutions show that the existence of shock waves in the SL parameter regime is very sensitive to these factors.
Furthermore, we show that even without shock waves, the reflection of continuous compressional waves at the bubble center can produce the high temperature and picosecond time scale light pulse of the SL bubble, which implies that SL may not necessarily be due to shock waves
Aquatic Birnavirus-Induced ER Stress-Mediated Death Signaling Contribute to Downregulation of Bcl-2 Family Proteins in Salmon Embryo Cells
Aquatic birnavirus induces mitochondria-mediated cell death, but whether connects to endoplasmic reticulum (ER) stress is still unknown. In this present, we characterized that IPNV infection triggers ER stress-mediated cell death via PKR/eIF2α phosphorylation signaling for regulating the Bcl-2 family protein expression in fish cells. The IPNV infection can induce ER stress as follows: (1) ER stress sensor ATF6 cleavaged; (2) ER stress marker GRP78 upregulation, and (3) PERK/eIF2αphosphorylation. Then, the IPNV-induced ER stress signals can induce the CHOP expression at early (6 h p.i.) and middle replication (12 h p.i.) stages. Moreover, IPNV-induced CHOP upregulation dramatically correlates to apparently downregulate the Bcl-2 family proteins, Bcl-2, Mcl-1 and Bcl-xL at middle replication stage (12 h p.i.) and produces mitochondria membrane potential (MMP) loss and cell death. Furthermore, with GRP78 synthesis inhibitor momitoxin (VT) and PKR inhibitor 2-aminopurine (2-AP) treatment for blocking GRP78 expression and eIF2α phosphorylation, PKR/PERK may involve in eIF2α phosphorylation/CHOP upregulation pathway that enhances the downstream regulators Bcl-2 family proteins expression and increased cell survival. Taken together, our results suggest that IPNV infection activates PKR/PERK/eIF2α ER stress signals for regulating downstream molecules CHOP upregulation and Bcl-2 family downregulation that led to induce mitochondria-mediated cell death in fish cells, which may provide new insight into RNA virus pathogenesis and disease
Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection
Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome
Robust estimation of microbial diversity in theory and in practice
Quantifying diversity is of central importance for the study of structure,
function and evolution of microbial communities. The estimation of microbial
diversity has received renewed attention with the advent of large-scale
metagenomic studies. Here, we consider what the diversity observed in a sample
tells us about the diversity of the community being sampled. First, we argue
that one cannot reliably estimate the absolute and relative number of microbial
species present in a community without making unsupported assumptions about
species abundance distributions. The reason for this is that sample data do not
contain information about the number of rare species in the tail of species
abundance distributions. We illustrate the difficulty in comparing species
richness estimates by applying Chao's estimator of species richness to a set of
in silico communities: they are ranked incorrectly in the presence of large
numbers of rare species. Next, we extend our analysis to a general family of
diversity metrics ("Hill diversities"), and construct lower and upper estimates
of diversity values consistent with the sample data. The theory generalizes
Chao's estimator, which we retrieve as the lower estimate of species richness.
We show that Shannon and Simpson diversity can be robustly estimated for the in
silico communities. We analyze nine metagenomic data sets from a wide range of
environments, and show that our findings are relevant for empirically-sampled
communities. Hence, we recommend the use of Shannon and Simpson diversity
rather than species richness in efforts to quantify and compare microbial
diversity.Comment: To be published in The ISME Journal. Main text: 16 pages, 5 figures.
Supplement: 16 pages, 4 figure
The Inviscid Limit and Boundary Layers for Navier-Stokes Flows
The validity of the vanishing viscosity limit, that is, whether solutions of
the Navier-Stokes equations modeling viscous incompressible flows converge to
solutions of the Euler equations modeling inviscid incompressible flows as
viscosity approaches zero, is one of the most fundamental issues in
mathematical fluid mechanics. The problem is classified into two categories:
the case when the physical boundary is absent, and the case when the physical
boundary is present and the effect of the boundary layer becomes significant.
The aim of this article is to review recent progress on the mathematical
analysis of this problem in each category.Comment: To appear in "Handbook of Mathematical Analysis in Mechanics of
Viscous Fluids", Y. Giga and A. Novotn\'y Ed., Springer. The final
publication is available at http://www.springerlink.co
Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis
Megakaryocytopoiesis is a complex differentiation process driven by the hormone
thrombopoietin by which haematopoietic progenitor cells give rise to
megakaryocytes, the giant bone marrow cells that in turn break down to form blood
platelets. The Tribbles Pseudokinase 3 gene (TRIB3) encodes a pleiotropic protein
increasingly implicated in the regulation of cellular differentiation programmes.
Previous studies have hinted that TRIB3 could be also involved in
megakaryocytopoiesis but its role in this process has so far not been investigated.
Using cellular model systems of haematopoietic lineage differentiation here we
demonstrate that TRIB3 is a negative modulator of megakaryocytopoiesis. We found
that in primary cultures derived from human haematopoietic progenitor cells,
thrombopoietin-induced megakaryocytic differentiation led to a time and dosedependent
decrease in TRIB3 mRNA levels. In the haematopoietic cell line UT7/mpl,
silencing of TRIB3 increased basal and thrombopoietin-stimulated megakaryocyte
antigen expression, as well as basal levels of ERK1/2 phosphorylation. In primary
haematopoietic cell cultures, silencing of TRIB3 facilitated megakaryocyte
differentiation. In contrast, over-expression of TRIB3 in these cells inhibited the
differentiation process. The in-vitro identification of TRIB3 as a negative regulator of
megakaryocytopoiesis suggests that in-vivo this gene could be important for the
regulation of platelet production
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