Unknown Effect Research Articles

Influence of resin cement shade on the color and translucency of zirconia crowns.

BackgroundZirconia crowns are highly attractive for clinicians, although have poor translucency when used as single restorations, in addition to unknown effect of resin cement shade on final cemented crown shade. This study aimed to assess effect of resin cement opacity on color replication potential of different zirconia frameworks with target tooth color, in addition to different zirconia crowns translucency evaluation. Material and MethodsTwenty-four zirconia crown restorations were fabricated to restore single central maxillary incisor for 8 patients, divided into 3 groups according to color and type of zirconia used (white Zr core, colored Zr core and monolithic HT Zrcowns). Each group was further subdivided into 2 subgroups according to resin cement shade. Using Easyshade spectrophotometer, Delta E color difference was calculated between each crown parameters using 2 different resin luting cement shades and adjacent target tooth. Translucency parameters (TP) were tested for finished crowns. ΔEs obtained were assessed based on ΔEof 1.6 which represented color difference that could not be detected by human eye and considered clinically acceptable. ResultsNo statistically significant values were found between subgroups related to different resin cement shade. Translucency parameters showed statistically significant different values. Monolithic crowns showed highest translucency parameters followed by Zr crowns on white cores then Zr crowns on colored cores. ConclusionsResin cement shade didn’t affect final color perception. Monolithic high translucency crowns usage gained advantages of high translucency and delamination prevention. Zirconia crowns could be cemented by opaque or transparent cement without affecting final color. Key words:Zirconia, resin cement, monolithic, translucency, spectrophotometer, Delta E.

Microenvironmental topographic cues influence migration dynamics of nasopharyngeal carcinoma cells from tumour spheroids.

Tumour metastasis is a complex process that strongly influences the prognosis and treatment of cancer. Apart from intracellular factors, recent studies have indicated that metastasis also depends on microenvironmental factors such as the biochemical, mechanical and topographical properties of the surrounding extracellular matrix (ECM) of tumours. In this study, as a proof of concept, we conducted tumour spheroid dissemination assay on engineered surfaces with micrograting patterns. Nasopharyngeal spheroids were generated by the 3D culture of nasopharyngeal carcinoma (NPC43) cells, a newly established cell line that maintains a high level of Epstein–Barr virus, a hallmark of NPC. Three types of collagen I-coated polydimethylsiloxane (PDMS) substrates were used, with 15 μm deep “trenches” that grated the surfaces: (a) 40/10 μm ridges (R)/trenches (T), (b) 18/18 μm (R/T) and (c) 50/50 μm (R/T). The dimensions of these patterns were designed to test how various topographical cues, different with respect to the size of tumour spheroids and individual NPC43 cells, might affect dissemination behaviours. Spreading efficiencies on all three patterned surfaces, especially 18/18 μm (R/T), were lower than that on flat PDMS surface. The outspreading cell sheets on flat and 40/10 μm (R/T) surfaces were relatively symmetrical but appeared ellipsoid and aligned with the main axes of the 18/18 μm (R/T) and 50/50 μm (R/T) grating platforms. Focal adhesions (FAs) were found to preferentially formed on the ridges of all patterns. The number of FAs per spheroid was strongly influenced by the grating pattern, with the least FAs on the 40/10 μm (R/T) and the most on the 50/50 μm (R/T) substrate. Taken together, these data indicate a previously unknown effect of surface topography on the efficiency and directionality of cancer cell spreading from tumour spheroids, suggesting that topography, like ECM biochemistry and stiffness, can influence the migration dynamics in 3D cell culture models.

О возможности получения оптимального порядка точности при восстановлении воздействия динамическим методом

Yu. S. Osipov and A. V. Kryazhimsky proposed a method of dynamic regulationto restore an unknown effect in a controlled model. In the framework of this approach, inthe present work we study the property of another method based on the use of the implicitEuler method for the problem of numerical differentiation. The choice of the parameters ofthe method is indicated, which makes it possible to increase its efficiency, reduce the noiselevel of the approximate solution, and obtain the optimal order of accuracy in the metricL(T); equal to 1/2.

Immune stimulatory effect of anti-EpCAM immunotoxin – improved overall survival of metastatic colorectal cancer patients

Introduction: In a recent phase I trial in a heterogeneous group of carcinoma patients with advanced disease, we did not observe objective responses by CT at 8 weeks in patients treated with either the anti-EpCAM immunotoxin MOC31PE alone or administered in combination with the immunosuppressor cyclosporin (CsA). We have now assessed overall survival (OS) data for the two groups to reveal potential differences, and to elucidate putative underlying mechanisms.Material and methods: The OS time of MOC31PE monotherapy (34 patients) and MOC31PE in combination with CsA (23 patients), was assessed. Pre- and post-treatment patient sera were analyzed in a multiplex immunoassay, and the immunogenic effects of MOC31PE were studied in vitro and in a dendritic cell maturation assay.Results: When the data were analyzed for all treated patients regardless of cancer type, the MOC31PE alone group had a median OS of 12.7 months (95% CI = 5.6–19.8 months) compared to 6.2 months (95% CI = 5.6–6.8 months) (p=.066) for the patients treated with MOC31PE + CsA group. For the subgroup of patients with colorectal cancer, the median OS survival was 16.3 months (95% CI = 5.6–27.0) for the MOC31PE only cohort (n = 15), compared to 6.0 months (CI = 5.8–6.2) (p < .001) for the combination group. The cytokine profile in patient sera and the in vitro immunological studies indicate that MOC31PE induced an immunogenic response leading to T-cell activation; a response that was suppressed in patients treated with MOC31PE + CsA.Conclusions: The results reveal a promising clinical benefit of anti-EpCAM immunotoxin treatment in patients with advanced disease, an effect apparently explained by a previously unknown immunogenic effect of MOC31PE.

Rivaroxaban Reduces Arterial Thrombosis by Inhibition of FXa-Driven Platelet Activation via Protease Activated Receptor-1.

A reduced rate of myocardial infarction has been reported in patients with atrial fibrillation treated with FXa (factor Xa) inhibitors including rivaroxaban compared with vitamin K antagonists. At the same time, low-dose rivaroxaban has been shown to reduce mortality and atherothrombotic events in patients with coronary artery disease. Yet, the mechanisms underlying this reduction remain unknown. In this study, we hypothesized that rivaroxaban's antithrombotic potential is linked to a hitherto unknown rivaroxaban effect that impacts on platelet reactivity and arterial thrombosis. In this study, we identified FXa as potent, direct agonist of the PAR-1 (protease-activated receptor 1), leading to platelet activation and thrombus formation, which can be inhibited by rivaroxaban. We found that rivaroxaban reduced arterial thrombus stability in a mouse model of arterial thrombosis using intravital microscopy. For in vitro studies, atrial fibrillation patients on permanent rivaroxaban treatment for stroke prevention, respective controls, and patients with new-onset atrial fibrillation before and after first intake of rivaroxaban (time series analysis) were recruited. Platelet aggregation responses, as well as thrombus formation under arterial flow conditions on collagen and atherosclerotic plaque material, were attenuated by rivaroxaban. We show that rivaroxaban's antiplatelet effect is plasma dependent but independent of thrombin and rivaroxaban's anticoagulatory capacity. Here, we identified FXa as potent platelet agonist that acts through PAR-1. Therefore, rivaroxaban exerts an antiplatelet effect that together with its well-known potent anticoagulatory capacity might lead to reduced frequency of atherothrombotic events and improved outcome in patients.

Design of Robust Trackers and Unknown Nonlinear Perturbation Estimators for a Class of Nonlinear Systems: HTRDNA Algorithm for Tracker Optimization

A robust linear quadratic analog tracker (LQAT) consisting of proportional-integral-derivative (PID) controller, sliding mode control (SMC), and perturbation estimator is proposed for a class of nonlinear systems with unknown nonlinear perturbation and direct feed-through term. Since the derivative type (D-type) controller is very sensitive to the state varying, a new D-type controller design algorithm is developed to avoid an unreasonable large value of the controller gain. Moreover, the boundary of D-type controller is discussed. To cope with the unknown perturbation effect, SMC is utilized. Based on the fast response of SMC controlled systems, the proposed perturbation estimator can estimate unknown nonlinear perturbation and improve the tracking performance. Furthermore, in order to tune the PID controller gains in the designed tracker, the nonlinear perturbation is eliminated by the SMC-based perturbation estimator first, then a hybrid Taguchi real coded DNA (HTRDNA) algorithm is newly proposed for the PID controller optimization. Compared with traditional DNA, a new HTRDNA is developed to improve the convergence performance and effectiveness. Numerical simulations are given to demonstrate the performance of the proposed method.

Search for Natural Compounds That Increase Apolipoprotein A-I Transcription in HepG2 Cells: Specific Attention for BRD4 Inhibitors.

Although increasing apolipoprotein A‐I (apoA‐I) might lower the cardiovascular disease risk, knowledge on natural compounds that elevate apoA‐I transcription is limited. Therefore, the aim of this study was to discover natural compounds that increase apoA‐I transcription in HepG2 cells. Since BRD4 inhibition is known to elevate apoA‐I transcription, we focused on natural BRD4 inhibitors. For this, the literature was screened for compounds that might increase apoA‐I and or inhibit BRD4. This resulted in list A, (apoA‐I increasers with unknown BRD4 inhibitor capacity), list B (known BRD4 inhibitors that increase apoA‐I), and list C (BRD4 inhibitors with unknown effect on apoA‐I). These compounds were compared with the compounds in two natural compound databases. This resulted in (1) a common substructure (ethyl‐benzene) in 60% of selected BRD4‐inhibitors, and (2) four compounds that increased ApoA‐I: hesperetin, equilenin, 9(S)‐HOTrE, and cymarin. Whether these increases are regulated via BRD4 inhibition and the ethyl‐benzene structure inhibits BRD4 requires further study.

PEGylated gold nanorods are not cytotoxic to human endothelial cells but affect kruppel-like factor signaling pathway

Gold (Au) nanomaterials (NMs), particularly those with PEG surface functionalization, are generally considered to be biocompatible for biomedical applications due to relatively low cytotoxicity. Herein, we investigated the toxicity of PEGylated Au nanorods (NRs) to human umbilical vein endothelial cells (HUVECs), a commonly used in vitro model for human endothelium. We found a previously unknown effect that up to 10 μg/mL Au NRs, albeit not cytotoxic, decreased the mRNA and protein levels of kruppel-like factor 2 (KLF2), a transcription factor with well-documented vasoprotective effects. The results from PCR array showed that a number of genes associated with risk of cardiovascular diseases were altered by Au NRs, and several genes are downstream genes of KLF2 according to ingenuity pathway analysis (IPA). These effects could be observed with or without the presence of inflammatory stimuli lipopolysaccharide (LPS), which suggests a pre-existing inflammatory state is not required for Au NRs to alter KLF2 signaling pathway. We further identified that Au NRs significantly decreased eNOS mRNA/p-eNOS proteins as well as increased MCP-1 mRNA/sMCP-1 release, which are targets of KLF2. Combined, our data revealed a novel pathway that PEGylated Au NPs at non-cytotoxic concentrations might alter KLF leading to the increase of risk of cardiovascular diseases in human endothelial cells. Given the importance of KLF in vascular homeostasis, our data indicate that it is necessary to evaluate the influence of engineered NPs to KLF signaling pathways, especially for NPs with biomedical uses.

Accounting for Correlations When Fitting Extra Cosmological Parameters

Abstract Current cosmological tensions motivate investigating extensions to the standard Λ cold dark matter (ΛCDM) model. Additional model parameters are typically varied one or two at a time, in a series of separate tests. The purpose of this paper is to highlight that information is lost by not also examining the correlations between these additional parameters, which arise when their effects on model predictions are similar even if the parameters are not varied simultaneously. We show how these correlations can be quantified with simulations and Markov Chain Monte Carlo methods. As an example, we assume that ΛCDM is the true underlying model, and calculate the correlations expected between the phenomenological lensing amplitude parameter, A L , the running of the spectral index, n run, and the primordial helium mass fraction, Y P , when these parameters are varied one at a time along with the ΛCDM parameters in fits to the Planck 2015 temperature power spectrum. These correlations are not small, ranging from 0.31 (A L −n run) to −0.93 (n run–Y P ). We find that the values of these three parameters from the Planck data are consistent with ΛCDM expectations within 0.9σ when the correlations are accounted for. This does not explain the 1.8–2.7σ Planck preference for A L &gt; 1, but provides an additional ΛCDM consistency test. For example, if A L &gt; 1 was a symptom of an underlying systematic error or some real but unknown physical effect that also produced spurious correlations with n run or Y P our test might have revealed this. We recommend that future cosmological analyses examine correlations between additional model parameters in addition to investigating them separately, one a time.

Outcomes and Predictors of Mortality in Hospitalized Frail Patients Undergoing Percutaneous Coronary Intervention.

ObjectiveTo study the impact of frailty on inpatient outcomes among patients undergoing percutaneous coronary intervention (PCI).MethodsThe National Inpatient Sample data of all PCI-related hospitalizations throughout the United States (US) from 2010 through 2014 was utilized. Patients were divided into two groups: frailty and no-frailty. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes were used to stratify groups and outcomes. In order to address the substantial difference in the total number of valid observations between the two groups, a propensity-matched analysis was performed at a 1:1 ratio and caliper width of 0.01.ResultsA total of 2,612,661 PCI-related hospitalizations throughout the US from 2010 through 2014 were identified, out of which 16,517 admissions (0.6%) had coexisting frailty. Only 1:1 propensity-matched data was utilized for the study. Propensity-matched frailty group (n=14,717) as compared to no-frailty (n=14,755) was frequently older, white, and Medicare enrollee (p<0.05). The frailty group had significantly higher rates of comorbidities and complications (p<0.05). All-cause in-hospital mortality was higher in the no-frailty group (p<0.05). Age, white race, non-elective admission, urban hospitals, and comorbidities predicted in-hospital mortality in frailty group (p<0.05). Rheumatoid arthritis, depression, hypertension, obesity, dyslipidemia, and history of previous PCI decreased odds of in-hospital mortality in frailty group (p<0.05). Frailty group had prolonged hospital stay and higher hospital charges (p<0.05).ConclusionsFrailty has a significant effect on PCI-related outcomes. We present a previously unknown protective effect of cardiovascular disease risk factors and other health risk factors on frail patients undergoing PCI. Frailty’s inclusion in risk stratification will help in predicting the post-procedure complications and improve resource utilization.

Ursodeoxycholic acid inhibits ENaC and Na/K pump activity to restore airway surface liquid height in cystic fibrosis bronchial epithelial cells

Cystic fibrosis (CF) is a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that in the airways result in reduced Cl− secretion and increased Na+ absorption, airway surface liquid (ASL) dehydration, decreased mucociliary clearance, infection and inflammation leading to lung injury. Cystic fibrosis patients often present with bile acids in the lower airways, however the effects of bile acids on ASL and ion transport in CF airways are not known. Secondary bile acids, such as ursodeoxycholic acid (UDCA), have been shown to modulate immune responses and epithelial ion transport. Here we investigated the effects of UDCA in normal and CF airway epithelial cell models. NuLi-1 (normal genotype) and CuFi-1 (CF genotype, Δ508/Δ508) primary immortalized airway epithelial cells were grown under an air-liquid interface. Electrogenic transepithelial ion transport was measured by short-circuit current (Isc) across cell monolayers mounted in Ussing chambers. We observed that UDCA (500 μM, 60 min, bilateral) decreased the basal Isc and ENaC currents in both NuLi-1 and CuFi-1 cells. UDCA inhibited the amiloride-sensitive ENaC current by 44% in NulI-1 monolayers and by 30% in CuFi-1 cells. Interestingly, UDCA also inhibited currents through the basolateral Na/K pump in both Nuli-1 and CuFi-1 monolayers without alterting the expression of ENaC or Na+/K+-ATPase proteins. The airway surface liquid height is regulated by transpeithelial Na+ absorption (ENaC) and Cl− secretion (CFTR) in normal airway but mainly by ENaC activity in CF epithelia when Cl− secretion is compromised by CFTR mutations. UDCA increased ASL height by 50% in Nuli-1 and by 40% in CUFI-1 monolayers. In conclusion, we demonstrate a previously unknown effect of UDCA to inhibit ENaC activity and increase ASL height in normal and CF human airway epithelial cells suggesting a therapeutic potential for UDCA in CF lung disease.

Follicle-stimulating hormone promotes renal tubulointerstitial fibrosis in aging women via the AKT/GSK-3β/β-catenin pathway.

Estrogen withdrawal in aging women contributes to the progression of chronic kidney disease (CKD). However, the effect of high circulating follicle‐stimulating hormone (FSH) levels on renal dysfunction remains unknown. In this study, blood samples from 3,055 postmenopausal women were collected and tested, which showed that there was a strong negative correlation between eGFR and FSH levels (p < 0.001), independent of LH, testosterone, and estradiol. Functional FSHR was detected in renal tubular epithelial cells. In vivo, high circulating FSH levels promoted a phenotype of tubulointerstitial fibrosis, characterized by increases in 24‐hr urine protein/creatinine ratio, serum Cr, serum BUN, and ECM deposition. Similar results obtained from cultured HK‐2 cells showed that FSH increased the transcriptional and protein expression of profibrotic mediators (collagen IV, fibronectin, and PAI‐1). This promotion of fibrosis by FSH occurred through the activation of AKT/GSK‐3β/β‐catenin pathway, which could be attenuated by silencing FSHR by siRNA or by LY294002 or MK2206. In addition, FSH‐stimulated HK‐2 cells secreted IL‐8, which promoted macrophage migration to exacerbate tubulointerstitial fibrosis. These results revealed a previously unknown effect of FSH on kidney injury, which may offer a critical insight into the development of CKD in aging postmenopausal women.

Procainamide Versus Amiodarone for Stable Ventricular Tachycardia.

Procainamide Versus Amiodarone for Stable Ventricular Tachycardia.

Dendrobium Officinale Polysaccharides Protect against MNNG-Induced PLGC in Rats via Activating the NRF2 and Antioxidant Enzymes HO-1 and NQO-1.

Dendrobium officinale polysaccharides (DOP) are the main effective ingredient in Dendrobium officinale. Nuclear factor erythroid 2-related factor 2 (NRF2) signaling is regarded as an important way to mitigate the effects of reactive oxygen species (ROS) damage and inhibit gastric cancer progress. This study introduces a previously unknown effect of DOP on precancerous lesions of gastric cancer (PLGC). The mechanism discussed herein is based on the NRF2 signal pathway as well as its downstream antioxidant enzymes heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase-1 (NQO-1). DOP was prepared by the alcohol deposition method, and its molecular weight was determined using High-Performance Gel-Permeation Chromatography (HPGPC). Sixty male rats were randomly divided into five groups: normal control group (NC), PLGC model group (PLGC), model treated with low dose (2.4 g/kg) of DOP (L-DOP), model treated with middle dose (4.8 g/kg) of DOP (M-DOP), and model treated with high dose (9.6 g/kg) of DOP (H-DOP). DOP was orally administered to rats for 15 consecutive days prior to the start of a seven-month course of 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) exposure. Histological evaluation was observed by hematoxylin and eosin (HE) and alcian blue/periodic acid-Schiff (AB-PAS) staining. Alanine aminotransferase (ALT), aspartate transaminase (AST), serum creatinine (Scr), serum uric acid (UA), blood urea nitrogen (BUN), and HE staining were detected for liver and kidney function. The level of 8-hydroxy-deoxyguanosine (8-OHdG) in serum was detected by kits. The NRF2 protein expression was detected by immunohistochemistry, and western blotting was utilized to compare differential protein expression levels among cytoplasmic and nuclear cell fractions. Expression levels of antioxidant enzymes heme oxygenase 1 (HO-1), Glutamate-Cysteine Ligase Catalytic Subunit (GCLC), Glutamate-Cysteine Ligase Modifier Subunit (GCLM), and NAD(P)H: quinone oxidoreductase-1 (NQO-1) were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR); furthermore, the protein expression of NRF2, HO-1, and NQO-1 was detected by western blotting. The results showed that the average content of DOP is 83%, and its molecular weight is mainly contained within 3500 and 1000000. The H-DOP experimental group exhibited noticeable weight gain after seven months, reduced intestinal metaplasia, and made the atypical hyperplasia to be kept in moderate or mild degree. Data also showed DOP to be capable of decreasing levels of ALT, UA, and BUN, all of which had been elevated following the appearance of MNNG-induced PLGCs. DOP was also seen to reduce the expression of 8-OHdG and promote the expression of NRF2 in the gastric mucosa. Furthermore, RT-PCR and western blotting results showed that DOP upregulated the gene and protein expression of HO-1 and NQO-1. These findings show that DOP prevents MNNG-induced PLGC along with subsequent liver and kidney damage. The protective effects of DOP are associated with the reduction of 8-OHdG levels as well as the activation of the NRF2 pathway and its related antioxidant enzymes, HO-1 and NQO-1.

MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer

In colorectal cancer (CRC), aberrant Wnt signalling is essential for tumorigenesis and maintenance of cancer stem cells. However, how other oncogenic pathways converge on Wnt signalling to modulate stem cell homeostasis in CRC currently remains poorly understood. Using large-scale compound screens in CRC, we identify MEK1/2 inhibitors as potent activators of Wnt/β-catenin signalling. Targeting MEK increases Wnt activity in different CRC cell lines and murine intestine in vivo. Truncating mutations of APC generated by CRISPR/Cas9 strongly synergize with MEK inhibitors in enhancing Wnt responses in isogenic CRC models. Mechanistically, we demonstrate that MEK inhibition induces a rapid downregulation of AXIN1. Using patient-derived CRC organoids, we show that MEK inhibition leads to increased Wnt activity, elevated LGR5 levels and enrichment of gene signatures associated with stemness and cancer relapse. Our study demonstrates that clinically used MEK inhibitors inadvertently induce stem cell plasticity, revealing an unknown side effect of RAS pathway inhibition.

Behaviour and design of circular hollow section steel columns strengthened by infilling concrete under preload

The objective of this work is to develop design guidance for existing hollow steel columns that are retrofitted by infilling concrete into the tubes. The primary challenge is the unknown effect of the existing preload on the steel columns prior to the concrete infill. Composite performance and buckling behaviour of circular hollow section (CHS) steel columns strengthened by infilling concrete under preload was experimentally and numerically investigated in this study. A total of 34 CHS steel columns were tested under pin-ended boundary conditions, and the overall buckling failure modes and corresponding ultimate buckling resistances were recorded. Prior to the member testing, material properties of the steel columns and the infilled concrete were attained. By means of the finite element (FE) software package ABAQUS, elaborate FE models for the CHS columns strengthened by infilling concrete were developed and validated against the obtained test results, which were further verified with other available test data. Using the validated FE models, systematic parametric studies were conducted to examine the influences of the major factors affecting the ultimate capacities of the CHS columns strengthened by infilling concrete, including preload ratios, steel and concrete strengths, steel ratios, initial global imperfections, eccentricity ratios and column slenderness ratios. The obtained test and numerical results were therefore utilised to develop design criteria for predicting the overall buckling resistance of CHS steel columns strengthened by infilling concrete. In view of the difficulty of determining the key parameters in practice and the uncertainty of the strengthening process, a new simplified design coefficient was proposed, taking into account the influence of the preload. It has been demonstrated that accurate and reasonable strength predictions can be provided by the proposed design method.

On prognostic estimates of radiation risk in medicine and radiation protection

The problem of expressing cumulative detrimental effect of radiation exposure is revisited. All conventionally used and computationally complex lifetime or time-integrated risks are based on current population and health statistical data, with unknown future secular trends, that are projected far into the future. It is shown that application of conventionally used lifetime or time-integrated attributable risks (LAR, AR) should be limited to exposures under 1 Gy. More general quantities, such as excess lifetime risk (ELR) and, to a lesser extent, risk of exposure-induced death (REID), are free of dose constraints, but are even more computationally complex than LAR and AR and rely on the unknown total radiation effect on demographic and health statistical data. Appropriate assessment of time-integrated risk of a specific outcome following high-dose (more than 1 Gy) exposure requires consideration of competing risks for other radiation-attributed outcomes and the resulting ELR estimate has an essentially non-linear dose response. Limitations caused by basing conventionally applied time-integrated risks on current population and health statistical data are that they are: (a) not well suited for risk estimates for atypical groups of exposed persons not readily represented by the general population; and (b) not optimal for risk projections decades into the future due to large uncertainties in developments of the future secular trends in the population-specific disease rates. Alternative disease-specific quantities, baseline and attributable survival fractions, based on reduction of survival chances are considered here and are shown to be very useful in circumventing most aspects of these limitations. Another main quantity, named as radiation-attributed decrease of survival (RADS), is recommended here to represent cumulative radiation risk conditional on survival until a certain age. RADS, historically known in statistical literature as “cumulative risk”, is only based on the radiation-attributed hazard and is insensitive to competing risks. Therefore, RADS is eminently suitable for risk projections in emergency situations and for estimating radiation risks for persons exposed after therapeutic or interventional medical applications of radiation or in other highly atypical groups of exposed persons, such as astronauts.

Sparse off-grid DOA estimation method with unknown mutual coupling effect

In the array systems, the mutual coupling effect between antennas degrades the estimation performance of direction of arrival (DOA) significantly. In this paper, the DOA estimation problem in a uniform linear array (ULA) is investigated, and a novel system model is formulated by exploiting the mutual coupling effect and the signal sparsity in the spatial domain. In the traditionally compressed sensing (CS)-based system model, the spatial domain is discretized into grids, and the off-grid gap limits the further improvement of the estimation performance. Therefore, the novel system model is proposed by considering both the off-grid problem and the unknown mutual coupling effect. Moreover, a novel algorithm, named sparse off-grid DOA estimation with unknown mutual coupling effect (SODMC), is proposed and updates the unknown parameters including the DOA, the mutual coupling vector, and the off-grid vector iteratively. Simulation results show that compared with state-of-the-art methods, the proposed SODMC algorithm improves the DOA estimation performance significantly in the scenario with unknown mutual coupling effect.

Simulated seawater flooding reduces oilseed rape growth, yield and progeny performance.

Of the many threats to global food security, one of the most pressing is the increased incidence of extreme weather events. In addition to extreme rainfall, a combination of global sea level rise and storm surge is likely to result in frequent episodes of seawater flooding in arable systems along low-lying coasts. Our aim was to elucidate the effects of simulated seawater and freshwater flooding on the survival, growth and reproductive potential of four cultivars of the important seed crop, Brassica napus [canola, or oilseed rape (OSR)]. Established plants were exposed to 24 or 96 h freshwater or seawater root zone immersion (with a no immersion 'control'). Initial post-treatment performance over 7 weeks was quantified using dry weight biomass. A second group of plants, cultivated until maturity, were used to quantify reproductive yield (siliqua and seed number, and seed size) and subsequent progeny performance (germination and seedling growth). Oilseed rape growth and reproductive responses were unaffected by freshwater, but seawater negatively affected growth and siliqua number for all cultivars, and seed mass for two ('Agatha' and 'Cubic'). In addition to impacts on crop yield, the growth of seedlings cultivated from seed collected from maternal plants subjected to seawater immersion was also reduced. Our results demonstrate the potential impact of seawater inundation on coastal cropping systems; although OSR may survive acute saline flooding, there are longer term impacts on growth and yield for some cultivars. The threat may necessitate changes in land-use practice and/or the development of salt-tolerant cultivars to maintain economically viable yields. In addition, by evidencing a hitherto unknown effect on reproductive performance (i.e. reduced seed yield) and subsequent seedling growth, our study highlights an important potential impact of coastal flooding on plant community dynamics for (semi-) natural habitats.

Systemic Administration of Avian Defensin 7: Distribution, Cellular Target, and Antibacterial Potential in Mice.

Defensins are natural antimicrobial peptides. The avian beta-defensin AvBD7 isolated from the chicken bone marrow possess broad antibacterial spectrum and strong resistance to proteolysis. However, its ability to fight systemic infections of major concern for public health, such as salmonellosis, is unknown. As a first approach, fluorescence labeling of AvBD7 allowed to track its systemic distribution after intraperitoneal injection in mice using whole body live imaging. It was associated to peritoneal cells and to deeper organs such as the liver. In the next step, the use of labeled AvBD7 allowed to observe its interaction with murine macrophages in culture. After incubation, it was able to penetrate inside the cells through an endocytosis-like mechanism. Furthermore, natural AvBD7 contributed to the control of intracellular multiplication of a multidrug resistant Salmonella strain, after incubation with infected macrophages. Finally, administration in a model of systemic lethal Salmonella infection in mice led to significant improvement of mouse survival, consistently with significant reduction of the liver bacterial load. In conclusion, the results reveal a hitherto unknown intracellular antibacterial effect of AvBD7 in Salmonella target cells and support AvBD7 as a candidate of interest for the treatment of infectious diseases caused by multidrug-resistant pathogenic Enterobacteriaceae.