3D models of radiatively driven colliding winds in massive O+O star binaries - II. Thermal radio to sub-mm emission

In this work the thermal emission over cm to sub-mm wavelengths from the winds in short-period O+O-star binaries is investigated (potential non-thermal emission is presently ignored). The calculations are based on three-dimensional hydrodynamical models which incorporate gravity, the driving of the winds, orbital motion of the stars, and radiative cooling of the shocked plasma. The thermal emission arises from the stellar winds and the region where they collide. We investigate the flux and spectrum from a variety of models as a function of orbital phase and orientation of the observer, and compare to the single star case. The emission from the wind-wind collision region (WCR) is strongly dependent on its density and temperature, being optically thick in radiative systems, and optically thin in adiabatic systems. The flux from systems where the WCR is highly radiative, as investigated for the first time in this work, can be over an order of magnitude greater than the combined flux from identically typed single stars. This excess occurs over a broad range of wavelengths from cm to sub-mm. In contrast, when the WCR is largely adiabatic, a significant excess in the thermal flux occurs only below 100 GHz. Eccentric systems may show order of magnitude or greater flux variability, especially if the plasma in the WCR transitions from an adiabatic to a radiative state and vice-versa - in such cases the flux can display significant hysteresis with stellar separation. We further demonstrate that clumping can affect the variability of radio lightcurves. We investigate the spectral index of the emission, and often find indices steeper than +0.6. Our predictions are of interest to future observations with the next generation of radio and sub-mm telescopes (abridged).Comment: 25 pages, 21 figures, accepted for publication in MNRA

Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers

BACKGROUND: In persons without clinical symptom it is difficult to assess an impact of probiotics regarding its effect on health. We evaluated the functional efficacy of the probiotic Lactobacillus fermentum ME-3 in healthy volunteers by measuring the influence of two different formulations on intestinal lactoflora, fecal recovery of the probiotic strain and oxidative stress markers of blood and urine after 3 weeks consumption. METHODS: Two 3-week healthy volunteer trials were performed. Open placebo controlled (OPC) study participants (n = 21) consumed either goat milk or by L. fermentum ME-3 fermented goat milk (daily dose 11.8 log CFU (Colony Forming Units). Double blind randomised placebo controlled (DBRP) study participants (n = 24) received either capsules with L. fermentum ME-3 (daily of dose 9.2 CFU) or placebo capsules. The faecal lactoflora composition, faecal ME-3 recovery, effect of the consumption on intestinal lactoflora, and oxidative stress markers of blood (total antioxidative activity; total antioxidative status and glutathione red-ox ratio) was measured. RESULTS: ME-3 was well tolerated and a significant increase in total faecal lactobacilli yet no predominance of ME-3 was detected in all study groups. Faecal recovery of ME-3 was documented by molecular methods only in fermented milk group, however the significant improvement of blood TAA (Total Antioxidative Activity) and TAS (Total Antioxidative Status) indices was seen both in case of fermented goat milk and capsules", yet glutathione re-ox ratio values decreased only in case of fermented by ME-3 goat milk. CONCLUSION: The functional efficacy of both consumed formulations of an antioxidative probiotic L. fermentum ME-3 is proved by the increase of the intestinal lactobacilli counts providing putative defence against enteric infections and by reduction of the oxidative stress indices of blood and urine of healthy volunteers. In non-diseased host the probiotic health claims can be assessed by improvement of some measurable laboratory indices of well-established physiological functions of host, e.g. markers of antioxidative defence system

3EG J2016+3657: Confirming an EGRET Blazar Behind the Galactic Plane

We recently identified the blazar-like radio source G74.87+1.22 (B2013+370) as the counterpart of the high-energy gamma-ray source 3EG J2016+3657 in the Galactic plane. However, since most blazar identifications of EGRET sources are only probabilistic in quality even at high Galactic latitude, and since there also exists a population of unidentified Galactic EGRET sources, we sought to obtain additional evidence to support our assertion that 3EG J2016+3657 is a blazar. These new observations consist of a complete set of classifications for the 14 brightest ROSAT X-ray sources in the error circle, of which B2013+370 remains the most likely source of the gamma-rays. We also obtained further optical photometry of B2013+370 itself which shows that it is variable, providing additional evidence of its blazar nature. Interestingly, this field contains, in addition to the blazar, the plerionic supernova remnant CTB 87, which is too distant to be the EGRET source, and three newly discovered cataclysmic variables, all five of these X-ray sources falling within 16' of each other. This illustrates the daunting problem of obtaining complete identifications of EGRET sources in the Galactic plane.Comment: 16 pages, 6 figures, accepted for publication in The Astrophysical Journa

Melanoma-specific antigen-associated antitumor antibody reactivity as an immune-related biomarker for targeted immunotherapies

Background:Immunotherapies, including cancer vaccines and immune checkpoint inhibitors have transformed the management of many cancers. However, a large number of patients show resistance to these immunotherapies and current research has provided limited findings for predicting response to precision immunotherapy treatments.Methods:Here, we applied the next generation phage display mimotope variation analysis (MVA) to profile antibody response and dissect the role of humoral immunity in targeted cancer therapies, namely anti-tumor dendritic cell vaccine (MelCancerVac®) and immunotherapy with anti-PD-1 monoclonal antibodies (pembrolizumab).Results:Analysis of the antibody immune response led to the characterization of epitopes that were linked to melanoma-associated and cancer-testis antigens (CTA) whose antibody response was induced upon MelCancerVac® treatments of lung cancer. Several of these epitopes aligned to antigens with strong immune response in patients with unresectable metastatic melanoma receiving anti-PD-1 therapy.Conclusions:This study provides insights into the differences and similarities in tumor-specific immunogenicity related to targeted immune treatments. The antibody epitopes as biomarkers reflect melanoma-associated features of immune response, and also provide insights into the molecular pathways contributing to the pathogenesis of cancer. Concluding, antibody epitope response can be useful in predicting anti-cancer immunity elicited by immunotherapy

WR 138: new results from X-ray and optical spectroscopy

Massive-binary evolution models predict that some systems will go through an evolutionary phase where the original primary has become a supernova and left a compact object behind that then orbits a Wolf-Rayet (WR) star. WR 138 is an X-ray bright WR star that has been described as a triple system, including a compact companion in a short-period orbit. Our goal is to search for spectroscopic evidence of a compact companion around WR 138. We used optical and X-ray spectra to search for signatures of a compact companion, which can be revealed by systematic variations in WR optical spectral lines induced by orbital motion of the compact companion or by hard, luminous X-rays from accretion onto this companion. The optical spectra display emission-line profile variations that are most probably caused by clumps inside the stellar winds. The radial velocities do not vary on a short time-scale compatible with the suggested orbital period of a putative compact companion. The X-ray spectra are found to be normal for a WN5-6+OB system with no indication of accretion by a compact companion. There is no evidence for the presence of a compact companion, and we therefore conclude that WR 138 is a normal long-period (P ~ 1521 d) eccentric WR+OB system.Peer reviewe

Effect of rosuvastatin on outcomes in chronic haemodialysis patients – design and rationale of the AURORA study

BACKGROUND: Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis. METHODS: More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been randomised (1:1), irrespective of baseline lipid levels, to treatment with rosuvastatin 10 mg or placebo. The primary study endpoint is the time to a major cardiovascular event (first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Secondary endpoints include all-cause mortality, major cardiovascular event-free survival time, time to cardiovascular death, time to non-cardiovascular death, cardiovascular interventions, tolerability of treatment and health economic costs per life-year saved. Study medication will be given until 620 subjects have experienced a major cardiovascular event. CONCLUSION: Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this expanding population

Oxidative Stress and Inflammation in Renal Patients and Healthy Subjects

The first goal of this study was to measure the oxidative stress (OS) and relate it to lipoprotein variables in 35 renal patients before dialysis (CKD), 37 on hemodialysis (HD) and 63 healthy subjects. The method for OS was based on the ratio of cholesteryl esters (CE) containing C18/C16 fatty acids (R2) measured by gas chromatography (GC) which is a simple, direct, rapid and reliable procedure. The second goal was to investigate and identify a triacylglycerol peak on GC, referred to as TG48 (48 represents the sum of the three fatty acids carbon chain lengths) which was markedly increased in renal patients compared to healthy controls. We measured TG48 in patients and controls. Mass spectrometry (MS) and MS twice in tandem were used to analyze the fatty acid composition of TG48. MS showed that TG48 was abundant in saturated fatty acids (SFAs) that were known for their pro-inflammatory property. TG48 was significantly and inversely correlated with OS. Renal patients were characterized by higher OS and inflammation than healthy subjects. Inflammation correlated strongly with TG, VLDL-cholesterol, apolipoprotein (apo) C-III and apoC-III bound to apoB-containing lipoproteins, but not with either total cholesterol or LDL-cholesterol

Lactobacillus fermentum ME-3 – an antimicrobial and antioxidative probiotic

The paper lays out the short scientific history and characteristics of the new probiotic Lactobacillus fermentum strain ME-3 DSM-14241, elaborated according to the regulations of WHO/FAO (2002). L. fermentum ME-3 is a unique strain of Lactobacillus species, having at the same time the antimicrobial and physiologically effective antioxidative properties and expressing health-promoting characteristics if consumed. Tartu University has patented this strain in Estonia (priority June 2001, patent in 2006), Russia (patent in 2006) and the USA (patent in 2007). The paper describes the process of the identification and molecular typing of this probiotic strain of human origin, its deposition in an international culture collection, and its safety assessment by laboratory tests and testing on experimental animals and volunteers. It has been established that L. fermentum strain ME-3 has double functional properties: antimicrobial activity against intestinal pathogens and high total antioxidative activity (TAA) and total antioxidative status (TAS) of intact cells and lysates, and it is characterized by a complete glutathione system: synthesis, uptake and redox turnover. The functional efficacy of the antimicrobial and antioxidative probiotic has been proven by the eradication of salmonellas and the reduction of liver and spleen granulomas in Salmonella Typhimurium-infected mice treated with the combination of ofloxacin and L. fermentum strain ME-3. Using capsules or foodstuffs enriched with L. fermentum ME-3, different clinical study designs (including double-blind, placebo-controlled, crossover studies) and different subjects (healthy volunteers, allergic patients and those recovering from a stroke), it has been shown that this probiotic increased the antioxidative activity of sera and improved the composition of the low-density lipid particles (LDL) and post-prandial lipids as well as oxidative stress status, thus demonstrating a remarkable anti-atherogenic effect. The elaboration of the probiotic L. fermentum strain ME-3 has drawn on wide international cooperative research and has taken more than 12 years altogether. The new ME-3 probiotic-containing products have been successfully marketed and sold in Baltic countries and Finland

Hemodialysis Removes Uremic Toxins That Alter the Biological Actions of Endothelial Cells

Chronic kidney disease is linked to systemic inflammation and to an increased risk of ischemic heart disease and atherosclerosis. Endothelial dysfunction associates with hypertension and vascular disease in the presence of chronic kidney disease but the mechanisms that regulate the activation of the endothelium at the early stages of the disease, before systemic inflammation is established remain obscure. In the present study we investigated the effect of serum derived from patients with chronic kidney disease either before or after hemodialysis on the activation of human endothelial cells in vitro, as an attempt to define the overall effect of uremic toxins at the early stages of endothelial dysfunction. Our results argue that uremic toxins alter the biological actions of endothelial cells and the remodelling of the extracellular matrix before signs of systemic inflammatory responses are observed. This study further elucidates the early events of endothelial dysfunction during toxic uremia conditions allowing more complete understanding of the molecular events as well as their sequence during progressive renal failure