Analysis of reactor burnup simulation uncertainties for antineutrino spectrum prediction

Nuclear reactors are a source of electron antineutrinos due to the presence of unstable fission products that undergo $\beta^-$ decay. They will be exploited by the JUNO experiment to determine the neutrino mass ordering and to get very precise measurements of the neutrino oscillation parameters. This requires the reactor antineutrino spectrum to be characterized as precisely as possible both through high resolution measurements, as foreseen by the TAO experiment, and detailed simulation models. In this paper we present a benchmark analysis utilizing Serpent Monte Carlo simulations in comparison with real pressurized water reactor spent fuel data. Our objective is to study the accuracy of fission fraction predictions as a function of different reactor simulation approximations. Then, utilizing the BetaShape software, we construct fissile antineutrino spectra using the summation method, thereby assessing the influence of simulation uncertainties on reactor antineutrino spectrum

Periodontal ligament cells as alternative source for cell-based therapy of tendon injuries: in vivo study of full-size Achilles tendon defect in a rat model

Tendon's natural healing potential is extremely low and inefficient, with significant dysfunction and disability due to hypocellularity and hypovascularity of tendon tissues. The application of stem cells can aid in significantly enhanced repair of tendon rupture; therefore, the main aim of this study is to assess the potential of using periodontal ligament cells (PDL), usually obtained from patients undergoing orthodontic treatment, as a novel cell source for cell-based therapy for tendon injuries in a clinically relevant rat full-size Achilles tendon defect. In addition, the study compares the differences between the healing effects of Achilles tendon-derived cells (AT) versus PDL and, hence, comprises of four experimental groups, native tendon (NT), empty defect (ED), PDL and human AT (hAT). The tendon healing in each group was assessed in the late remodelling phase at 16 weeks after surgery using a combination of methods, including evaluation of gross morphological appearance; various histological and immunohistological stainings; and detailed analyses of cell morphometry. Based on these outcome measures, PDL cell-implanted tendons exhibited not only advanced tissue maturation, less ectopic fibrocartilage formation, more organised collagen fibres, tendon matrix expression corresponding to the final healing stage, and better cell-morphometry parameters when compared with the ED group, but were also very similar to the tendons treated with hAT-derived cells. Taken together, our study clearly demonstrates the feasibility of using PDL cells as a novel cell source for tendon repair and strongly recommends this cell type for the future development of innovative regenerative applications for treatment of different tendon or ligament pathologies

Schistosoma mansoni-Mediated Suppression of Allergic Airway Inflammation Requires Patency and Foxp3+ Treg Cells

The continual rise of asthma in industrialised countries stands in strong contrast to the situation in developing lands. According to the modified Hygiene Hypothesis, helminths play a major role in suppressing bystander immune responses to allergens, and both epidemiological and experimental studies suggest that the tropical parasitic trematode Schistosoma mansoni elicits such effects. The focus of this study was to investigate which developmental stages of schistosome infection confer suppression of allergic airway inflammation (AAI) using ovalbumin (OVA) as a model allergen. Moreover, we assessed the functional role and localization of infection-induced CD4(+)Foxp3(+) regulatory T cells (Treg) in mediating such suppressive effects. Therefore, AAI was elicited using OVA/adjuvant sensitizations with subsequent OVA aerosolic challenge and was induced during various stages of infection, as well as after successful anti-helminthic treatment with praziquantel. The role of Treg was determined by specifically depleting Treg in a genetically modified mouse model (DEREG) during schistosome infection. Alterations in AAI were determined by cell infiltration levels into the bronchial system, OVA-specific IgE and Th2 type responses, airway hyper-sensitivity and lung pathology. Our results demonstrate that schistosome infection leads to a suppression of OVA-induced AAI when mice are challenged during the patent phase of infection: production of eggs by fecund female worms. Moreover, this ameliorating effect does not persist after anti-helminthic treatment, and depletion of Treg reverts suppression, resulting in aggravated AAI responses. This is most likely due to a delayed reconstitution of Treg in infected-depleted animals which have strong ongoing immune responses. In summary, we conclude that schistosome-mediated suppression of AAI requires the presence of viable eggs and infection-driven Treg cells. These data provide evidence that helminth derived products could be incorporated into treatment strategies that specifically target suppression of immune responses in AAI by inducing Treg cells

Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias

Background Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes. Aim To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro-oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms. Methods Thirty-two patients (13 females and 19 males; age: 20–69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43–58 years) with GERD only, underwent simultaneous 24-h pH-metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months fulldosage PPI therapy (esomeprazole 40 mg/day) was prescribed. Results In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P < 0.05) correlation between oesophageal pH and LF/HF ratio (oesophagus–heart correlation) was observed. A significant reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs. 4/11, P < 0.01). Conclusions This study has identified a subgroup of dysrhythmic patients in whom the oesophageal acid stimulus elicited cardiac autonomic reflexes. In these patients acid suppression seems to improve GERD and cardiac symptoms

Esophageal Acid Exposure and Altered Neurocardiac Function in Patients with GERD and Idiopatic Cardiac Arrhythmias

BACKGROUND: Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes. AIM: To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro-oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms. METHODS: Thirty-two patients (13 females and 19 males; age: 20-69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43-58 years) with GERD only, underwent simultaneous 24-h pH-metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months full-dosage PPI therapy (esomeprazole 40 mg/day) was prescribed. RESULTS: In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P < 0.05) correlation between oesophageal pH and LF/HF ratio (oesophagus-heart correlation) was observed. A significant reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs. 4/11, P < 0.01). CONCLUSIONS: This study has identified a subgroup of dysrhythmic patients in whom the oesophageal acid stimulus elicited cardiac autonomic reflexes. In these patients acid suppression seems to improve GERD and cardiac symptoms

Chronic schistosomiasis during pregnancy epigenetically reprograms T cell differentiation in offspring of infected mothers.

Schistosomiasis is a non-transplacental helminth infection. Chronic infection during pregnancy suppresses allergic airway responses in offspring. We addressed the question whether in utero exposure to chronic schistosome infection (Reg phase) in mice affects B cell and T cell development. Therefore, we focused our analysis on T cell differentiation capacity induced by epigenetic changes in promoter regions of signature cytokines in offspring. Here we show that na&iuml;ve T cells from offspring of schistosome infected female mice had a strong capacity to differentiate into TH 1 cells, whereas TH 2 differentiation was impaired. In accordance, reduced levels of histone acetylation of the IL-4 promoter regions were observed in na&iuml;ve T cells. To conclude, our mouse model revealed distinct epigenetic changes within the na&iuml;ve T cell compartment affecting TH 2 and TH 1 cell differentiation in offspring of mothers with chronic helminth infection. These findings could eventually help understand how helminths alter T cell driven immune responses induced by allergens, bacterial or viral infections, as well as vaccines

Schistosome infection aggravates HCV-related liver disease and induces changes in the regulatory T-cell phenotype.

© 2015 John Wiley &amp; Sons Ltd. Schistosome infections are renowned for their ability to induce regulatory networks such as regulatory T cells (Treg) that control immune responses against homologous and heterologous antigens such as allergies. However, in the case of co-infections with hepatitis C virus (HCV), schistosomes accentuate disease progression and we hypothesized that expanding schistosome-induced Treg populations change their phenotype and could thereby suppress beneficial anti-HCV responses. We therefore analysed effector T cells and n/iTreg subsets applying the markers Granzyme B (GrzB) and Helios in Egyptian cohorts of HCV mono-infected (HCV), schistosome-co-infected (Sm/HCV) and infection-free individuals. Interestingly, viral load and liver transaminases were significantly elevated in Sm/HCV individuals when compared to HCV patients. Moreover, overall Treg frequencies and HeliosposTreg were not elevated in Sm/HCV individuals, but frequencies of GrzB+Treg were significantly increased. Simultaneously, GrzB+ CD8+ T cells were not suppressed in co-infected individuals. This study demonstrates that in Sm/HCV co-infected cohorts, liver disease is aggravated with enhanced virus replication and Treg do not expand but rather change their phenotype with GrzB possibly being a more reliable marker than Helios for iTreg. Therefore, curing concurrent schistosome disease could be an important prerequisite for successful HCV treatment as co-infected individuals respond poorly to interferon therapy

Dynamic, helminth-induced immune modulation influences the outcome of acute and chronic hepatitis B virus infection.

Background. Chronic hepatitis B develops more frequently in countries with high prevalence of helminth infections. The crosstalk between these 2 major liver-residing pathogens, Schistosoma mansoni and hepatitis B virus (HBV), is barely understood.Methods. We used state-of-the-art models for both acute and chronic HBV infection to study the pathogen-crosstalk during the different immune phases of schistosome infection.Results. Although liver pathology caused by schistosome infection was not affected by either acute or chronic HBV infection, S mansoni infection influenced HBV infection outcomes in a phase-dependent manner. Interferon (IFN)-gamma secreting, HBV- and schistosome-specific CD8 T cells acted in synergy to reduce HBV-induced pathology during the T(H)1 phase and chronic phase of schistosomiasis. Consequently, HBV was completely rescued in IFN-gamma-deficient or in T(H)2 phase coinfected mice demonstrating the key role of this cytokine. It is interesting to note that secondary helminth infection on the basis of persistent (chronic) HBV infection increased HBV-specific T-cell frequency and resulted in suppression of virus replication but failed to fully restore T-cell function and eliminate HBV.Conclusions. Thus, schistosome-induced IFN-gamma had a prominent antiviral effect that outcompeted immunosuppressive effects of T(H)2 cytokines, whereas HBV coinfection did not alter schistosome pathogenicity

Experimental models for examining <i>S. mansoni</i>-mediated suppression of AAI.

<p>A <i>Patent Infected Protection (PiP)</i>. Groups of BALB/c female mice were infected with <i>S. mansoni</i>. Inf/OVA and OVA groups of mice were then sensitised with OVA either i.p. with Alum or s.c. without adjuvant at the indicated timepoints. Challenge occurred over three consecutive days in the 9th week of infection and analysis 5 days thereafter. B <i>Prepatent (PP</i>). Sensitizations were started in Inf/OVA and OVA groups during the first weeks of infection, before eggs are released from fecund females. Challenge and analysis were performed as in A. C <i>Early Phase (EP)</i>. AAI was performed entirely over the first 5 weeks of infection. D <i>Praziquantel therapy</i>. During the 6th week of infection, mice were orally treated with PZQ for 5 consecutive days. AAI was then begun after either 2 weeks (upper track) or 6 weeks (lower track). E <i>Depletion of Treg</i>. Groups of C57BL/6 DEREG mice were infected with <i>S. mansoni</i>. In some groups, Treg were depleted using DT injections prior to OVA sensitization at the indicated timepoints. Challenge and analysis occurred in the 12th week of infection.</p