Effect of energy deposition modelling in coupled steady state Monte Carlo neutronics/thermal hydraulics calculations

In coupled calculations with Monte Carlo neutronics and thermal hydraulics the Monte Carlo code is used to produce a power distribution which in practice means tallying the energy deposition. Usually the energy deposition is estimated by making a simple approximation that energy is deposited only in fission reactions. The goal of this work is to study how the accuracy of energy deposition modelling affects the results of steady state coupled calculations. For this task an internal coupling between Monte Carlo transport code Serpent 2 and subchannel code SUBCHANFLOW is used along with a recently implemented energy deposition treatment of Serpent 2. The new treatment offers four energy deposition modes each of which offers a different combination of accuracy and required computational time. As a test case, a 3D PWR fuel assembly is modelled with different energy deposition modes. The resulting effective multiplication factors are within 30 pcm. Differences of up to 100K are observed in the fuel temperatures

Factors associated with severity of atopic dermatitis – a Finnish cross-sectional study

Publisher Copyright: © 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.Background: Severity-associated factors in atopic dermatitis (AD) have focussed on early onset, concomitant atopic diseases, markers of Th2-shifted inflammation and filaggrin mutations. Objectives: To investigate factors associated with severe AD in Finnish patients. Methods: We conducted a single-centre, cross-sectional observational study with 502 AD patients aged 4.79 to 79.90 years (mean 32.08 years). Disease severity was assessed with the Rajka–Langeland severity score and EASI and associated clinical signs were evaluated. Data regarding onset, relatives, atopic and other comorbidities was gathered retrospectively. We investigated total serum IgE-levels, a panel of filaggrin null mutations and functional variants of genes associated with skin barrier defects. Results: Factors more frequent in severe AD included early onset (P = 0.004, 95%CI 0.000–0.024), male sex (P = 0.002, 95%CI 0.000–0.11), history of smoking (P = 0.012, 95%CI 0.000–0.024), concomitant asthma (P = 0.001, 95%CI 0.000–0.011), palmar hyperlinearity (P = 0.013, 95%CI 0.014–0.059), hand dermatitis (P = 0.020, 95%CI 0.000–0.029) and history of contact allergy (P = 0.042, 95%CI 0.037–0.096). Body mass indices (P < 0.000, 95%CI 0.000–0.011) and total serum IgE-levels (P < 0.000, 95%CI 0.000–0.011) were higher in severe AD. No differences were observed for allergic rhinitis, allergic conjunctivitis, food allergy, peanut allergy, prick positivity, keratosis pilaris, history of herpes simplex infections, filaggrin null mutations and other gene variants. Conclusions: Severity determinants in Finnish patients seem to be early-onset, male sex, smoking, overweight, concomitant asthma, palmar hyperlinearity, hand dermatitis and high IgE-levels. A sub-typing of patients in relation to confirmed severity determinants may be useful for course prediction, prognosis and targeted AD management.Peer reviewe

Real-time analysis of the binding of fluorescent VEGF₁₆₅a to VEGFR2 in living cells: Effect of receptor tyrosine kinase inhibitors and fate of internalized agonist-receptor complexes

Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. Here we have used a novel stoichiometric protein-labeling method to generate a fluorescent variant of VEGF (VEGF₁₆₅a-TMR) labeled on a single cysteine within each protomer of the antiparallel VEGF homodimer. VEGF₁₆₅a-TMR has then been used in conjunction with full length VEGFR2, tagged with the bioluminescent protein NanoLuc, to undertake a real time quantitative evaluation of VEGFR2 binding characteristics in living cells using bioluminescence resonance energy transfer (BRET). This provided quantitative information on VEGF-VEGFR2 interactions. At longer incubation times, VEGFR2 is internalized by VEGF₁₆₅a-TMR into intracellular endosomes. This internalization can be prevented by the receptor tyrosine kinase inhibitors (RTKIs) cediranib, sorafenib, pazopanib or vandetanib. In the absence of RTKIs, the BRET signal is decreased over time as a consequence of the dissociation of agonist from the receptor in intracellular endosomes and recycling of VEGFR2 back to the plasma membrane