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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 (∼65 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 1 year 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
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
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
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
Trafficking-Deficient G572R-hERG and E637K-hERG Activate Stress and Clearance Pathways in Endoplasmic Reticulum
Background: Long QT syndrome type 2 (LQT2) is the second most common type of all long QT syndromes. It is well-known that trafficking deficient mutant human ether-a-go-go-related gene (hERG) proteins are often involved in LQT2. Cells respond to misfolded and trafficking-deficient proteins by eliciting the unfolded protein response (UPR) and Activating Transcription Factor (ATF6) has been identified as a key regulator of the mammalian UPR. In this study, we investigated the role of ER chaperone proteins (Calnexin and Calreticulin) in the processing of G572R-hERG and E637K-hERG mutant proteins. Methods: pcDNA3-WT-hERG, pcDNA3-G572R-hERG and pcDNA3-E637K-hERG plasmids were transfected into U2OS and HEK293 cells. Confocal microscopy and western blotting were used to analyze subcellular localization and protein expression. Interaction between WT or mutant hERGs and Calnexin/Calreticulin was tested by coimmunoprecipitation. To assess the role of the ubiquitin proteasome pathway in the degradation of mutant hERG proteins, transfected HEK293 cells were treated with proteasome inhibitors and their effects on the steady state protein levels of WT and mutant hERGs were examined. Conclusion: Our results showed that levels of core-glycosylated immature forms of G572R-hERG and E637K-hERG in association with Calnexin and Calreticulin were higher than that in WT-hERG. Both mutant hERG proteins could activate the UPR by upregulating levels of active ATF6. Furthermore, proteasome inhibition increased the levels of core-glycosylated immature forms of WT and mutant hERGs. In addition, interaction between mutant hERGs and Calnexin/Calreticulin wa
Traditional Cantonese diet and nasopharyngeal carcinoma risk: a large-scale case-control study in Guangdong, China
<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carcinoma (NPC) is rare in most parts of the world but is a common malignancy in southern China, especially in Guangdong. Dietary habit is regarded as an important modifier of NPC risk in several endemic areas and may partially explain the geographic distribution of NPC incidence. In China, rapid economic development during the past few decades has changed the predominant lifestyle and dietary habits of the Chinese considerably, requiring a reassessment of diet and its potential influence on NPC risk in this NPC-endemic area.</p> <p>Methods</p> <p>To evaluate the association between dietary factors and NPC risk in Guangdong, China, a large-scale, hospital-based case-control study was conducted. 1387 eligible cases and 1459 frequency matched controls were recruited. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated using a logistic regression model, adjusting for age, sex, education, dialect, and habitation household type.</p> <p>Results</p> <p>Observations made include the following: 1) consumption of canton-style salted fish, preserved vegetables and preserved/cured meat were significantly associated with increased risk of NPC, with enhanced odds ratios (OR) of 2.45 (95% CI: 2.03-2.94), 3.17(95% CI: 2.68-3.77) and 2.09 (95% CI: 1.22-3.60) respectively in the highest intake frequency stratum during childhood; 2) consumption of fresh fruit was associated with reduced risk with a dose-dependent relationship (p = 0.001); and 3) consumption of Canton-style herbal tea and herbal slow-cooked soup was associated with decreased risk, with ORs of 0.84 (95% CI: 0.68-1.03) and 0.58 (95% CI: 0.47-0.72) respectively in the highest intake frequency stratum. In multivariate analyses, these associations remained significant.</p> <p>Conclusions</p> <p>It can be inferred that previously established dietary risk factors in the Cantonese population are still stable and have contributed to the incidence of NPC.</p
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