We report on the experimental observation of quantum-network-compatible light described by a nonpositive Wigner function. The state is generated by photon subtraction from a squeezed vacuum state ...produced by a continuous wave optical parametric amplifier. Ideally, the state is a coherent superposition of odd photon number states, closely resembling a superposition of weak coherent states |alpha > - |-alpha >. In the limit of low squeezing the state is basically a single photon state. Light is generated with about 10,000 and more events per second in a nearly perfect spatial mode with a Fourier-limited frequency bandwidth which matches well atomic quantum memory requirements. The generated state of light is an excellent input state for testing quantum memories, quantum repeaters, and linear optics quantum computers.
The objective was to use accumulated evidence to explore the association between processed meat intake and risk of colorectal cancer (CRC) and to investigate the reliability of associations by ...evaluating patterns of risk by study population characteristics and research quality parameters. We included 29 observational prospective cohort studies with relative risk estimates and 95% confidence intervals for CRC according to various levels of processed meat consumption. Risk of bias was assessed using Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. Data sources were PubMed and Embase up to January 2017. The summary relative risks for high versus low processed meat consumption and risk of CRC, colon, and rectal cancer were 1.13 (95% CI: 1.01, 1.26), 1.19 (95% CI: 1.09, 1.31), and 1.21 (95% CI: 0.98, 1.49), respectively. Similar estimates were observed for the dose-response analyses. Heterogeneity across studies was detected in most analytical models. The overall judgment showed that two out of 29 studies had a moderate risk of bias, 25 had a serious risk of bias, and 2 had a critical risk of bias. The bias domains most often rated critical were bias due to risk of confounding, bias due to missing data, and selective outcome reporting bias. Although this meta-analysis indicates a modest association between processed meat intake and an increased risk of CRC, our assessment of internal validity warrants a cautious interpretation of these results, as most of the included studies were judged to have serious or critical risks of bias.
A fully open source software program for automated two‐dimensional and one‐dimensional data reduction and preliminary analysis of isotropic small‐angle X‐ray scattering (SAXS) data is presented. The ...program is freely distributed, following the open‐source philosophy, and does not rely on any commercial software packages. BioXTAS RAW is a fully automated program that, via an online feature, reads raw two‐dimensional SAXS detector output files and processes and plots data as the data files are created during measurement sessions. The software handles all steps in the data reduction. This includes mask creation, radial averaging, error bar calculation, artifact removal, normalization and q calibration. Further data reduction such as background subtraction and absolute intensity scaling is fast and easy via the graphical user interface. BioXTAS RAW also provides preliminary analysis of one‐dimensional data in terms of the indirect Fourier transform using the objective Bayesian approach to obtain the pair‐distance distribution function, PDDF, and is thereby a free and open‐source alternative to existing PDDF estimation software. Apart from the TIFF input format, the program also accepts ASCII‐format input files and is currently compatible with one‐dimensional data files from SAXS beamlines at a number of synchrotron facilities. BioXTAS RAW is written in Python with C++ extensions.
DNA origami provides rapid access to easily functionalized, nanometer‐sized structures making it an intriguing platform for the development of defined drug delivery and sensor systems. Low cellular ...uptake of DNA nanostructures is a major obstacle in the development of DNA‐based delivery platforms. Herein, significant strong increase in cellular uptake in an established cancer cell line by modifying a planar DNA origami structure with the iron transport protein transferrin (Tf) is demonstrated. A variable number of Tf molecules are coupled to the origami structure using a DNA‐directed, site‐selective labeling technique to retain ligand functionality. A combination of confocal fluorescence microscopy and quantitative (qPCR) techniques shows up to 22‐fold increased cytoplasmic uptake compared to unmodified structures and with an efficiency that correlates to the number of transferrin molecules on the origami surface.
The uptake of a transferrin‐loaded 2D DNA origami structure into a cancer cell line correlates with the number of transferrin molecules on the structure. This may be used to enhance cell uptake of DNA nanostructures currently being harnessed as smart molecular vehicles in drug delivery.
ABSTRACT
The European Pulsar Timing Array (EPTA) collaboration has recently released an extended data set for six pulsars (DR2) and reported evidence for a common red noise signal. Here we present a ...noise analysis for each of the six pulsars. We consider several types of noise: (i) radio frequency independent, ‘achromatic’, and time-correlated red noise; (ii) variations of dispersion measure and scattering; (iii) system and band noise; and (iv) deterministic signals (other than gravitational waves) that could be present in the PTA data. We perform Bayesian model selection to find the optimal combination of noise components for each pulsar. Using these custom models we revisit the presence of the common uncorrelated red noise signal previously reported in the EPTA DR2 and show that the data still supports it with a high statistical significance. Next, we confirm that there is no preference for or against the Hellings–Downs spatial correlations expected for the stochastic gravitational-wave background. The main conclusion of the EPTA DR2 paper remains unchanged despite a very significant change in the noise model of each pulsar. However, modelling the noise is essential for the robust detection of gravitational waves and its impact could be significant when analysing the next EPTA data release, which will include a larger number of pulsars and more precise measurements.
Exaggerated postprandial secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) may explain appetite reduction and weight loss after Roux-en-Y gastric bypass (RYGB), but causality has not ...been established. We hypothesized that food intake decreases after surgery through combined actions from GLP-1 and PYY. GLP-1 actions can be blocked using the GLP-1 receptor antagonist Exendin 9-39 (Ex-9), whereas PYY actions can be inhibited by the administration of a dipeptidyl peptidase-4 (DPP-4) inhibitor preventing the formation of PYY
.
Appetite-regulating gut hormones and appetite ratings during a standard mixed-meal test and effects on subsequent ad libitum food intake were evaluated in two studies: in study 1, nine patients with type 2 diabetes were examined prospectively before and 3 months after RYGB with and without Ex-9. In study 2, 12 RYGB-operated patients were examined in a randomized, placebo-controlled, crossover design on four experimental days with: (1) placebo, (2) Ex-9, (3) the DPP-4 inhibitor, sitagliptin, to reduce formation of PYY
and (4) Ex-9/sitagliptin combined.
In study 1, food intake decreased by 35% following RYGB compared with before surgery. Before surgery, GLP-1 receptor blockage increased food intake but no effect was seen postoperatively, whereas PYY secretion was markedly increased. In study 2, combined GLP-1 receptor blockage and DPP-4 inhibitor mediated lowering of PYY
increased food intake by ~20% in RYGB patients, whereas neither GLP-1 receptor blockage nor DPP-4 inhibition alone affected food intake, perhaps because of concomitant marked increases in the unblocked hormone.
Blockade of actions from only one of the two L-cell hormones, GLP-1 and PYY
, resulted in concomitant increased secretion of the other, probably explaining the absent effect on food intake on these experimental days. Combined blockade of GLP-1 and PYY actions increased food intake after RYGB, supporting that these hormones have a role in decreased food intake postoperatively.
DNA-protein conjugates are important in bioanalytical chemistry, molecular diagnostics and bionanotechnology, as the DNA provides a unique handle to identify, functionalize or otherwise manipulate ...proteins. To maintain protein activity, conjugation of a single DNA handle to a specific location on the protein is often needed. However, preparing such high-quality site-specific conjugates often requires genetically engineered proteins, which is a laborious and technically challenging approach. Here we demonstrate a simpler method to create site-selective DNA-protein conjugates. Using a guiding DNA strand modified with a metal-binding functionality, we directed a second DNA strand to the vicinity of a metal-binding site of His6-tagged or wild-type metal-binding proteins, such as serotransferrin, where it subsequently reacted with lysine residues at that site. This method, DNA-templated protein conjugation, facilitates the production of site-selective protein conjugates, and also conjugation to IgG1 antibodies via a histidine cluster in the constant domain.
Despite several years of research and attempts to develop prognostic models a considerable fraction of stage II colon cancer patients will experience relapse within few years from their operation. ...The aim of the present study was to investigate the prognostic importance of miRNA-21 (miR-21), quantified by in situ hybridisation, in a unique, large population-based cohort.
The study included 764 patients diagnosed with stage II colon cancer in Denmark in the year 2003. One section from a representative paraffin-embedded tumour tissue specimen from each patient was processed for analysis of miR-21 and quantitatively assessed by image analysis.
The miR-21 signal was predominantly observed in fibroblast-like cells located in the stromal compartment of the tumours. We found that patients expressing high levels of miR-21 had significantly inferior recurrence-free cancer-specific survival (RF-CSS): HR=1.26; 95% CI: 1.15-1.60; P<0.001. In Cox regression analysis, a high level of miR-21 retained its prognostic importance and was found to be significantly related to poor RF-CSS: HR=1.41; 95% CI: 1.19-1.67; P<0.001.
The present study showed that increasing miR-21 expression levels were significantly correlated to decreasing RF-CSS. Further investigations of the clinical importance of miR-21 in the selection of high-risk stage II colon cancer patients are merited.
Context.
High-precision pulsar timing requires accurate corrections for dispersive delays of radio waves, parametrized by the dispersion measure (DM), particularly if these delays are variable in ...time. In a previous paper, we studied the solar wind (SW) models used in pulsar timing to mitigate the excess of DM that is annually induced by the SW and found these to be insufficient for high-precision pulsar timing. Here we analyze additional pulsar datasets to further investigate which aspects of the SW models currently used in pulsar timing can be readily improved, and at what levels of timing precision SW mitigation is possible.
Aims.
Our goals are to verify: (a) whether the data are better described by a spherical model of the SW with a time-variable amplitude, rather than a time-invariant one as suggested in literature, and (b) whether a temporal trend of such a model’s amplitudes can be detected.
Methods.
We use the pulsar timing technique on low-frequency pulsar observations to estimate the DM and quantify how this value changes as the Earth moves around the Sun. Specifically, we monitor the DM in weekly to monthly observations of 14 pulsars taken with parts of the LOw-Frequency ARray (LOFAR) across time spans of up to 6 years. We develop an informed algorithm to separate the interstellar variations in the DM from those caused by the SW and demonstrate the functionality of this algorithm with extensive simulations. Assuming a spherically symmetric model for the SW density, we derive the amplitude of this model for each year of observations.
Results.
We show that a spherical model with a time-variable amplitude models the observations better than a spherical model with a constant amplitude, but that both approaches leave significant SW-induced delays uncorrected in a number of pulsars in the sample. The amplitude of the spherical model is found to be variable in time, as opposed to what has been previously suggested.
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