Extreme events in the European renewable power system:Validation of a modeling framework to estimate renewable electricity production and demand from meteorological data

With the need to reduce greenhouse gas emissions, the coming decades will see a transition of Europe's power system, currently mainly based on fossil fuels towards a higher share of renewable sources. Increasing effects of fluctuations in electricity production and demand as a result of meteorological variability might cause compound events with unforeseen impacts. We constructed and validated a modeling framework to examine such extreme impact events on the European power system. This framework includes six modules: i) a reservoir hydropower inflow and ii) dispatch module; iii) a run-of-river hydropower production module; iv) a wind energy production module; v) a photovoltaic solar energy production model; and vi) an electricity demand module. Based on ERA5 reanalysis input data and present-day capacity distributions, we computed electricity production and demand for a set of European countries in the period 2015–2021 and compared results to observed data. The model captures the variability and extremes of wind, photovoltaic and run-of-river production well, with correlations between modelled and observed data for most countries of more than 0.87, 0.68 and 0.65 respectively. The hydropower dispatch module also functions well, with correlations up to 0.82, but struggles to capture reservoir inflows and operating procedures of some countries. A case study into the meteorological drivers of extreme events in Sweden and Spain showed that the meteorological conditions during extreme events selected by the model and extracted from observational data are similar, giving confidence in the application of the modeling framework for (future changes in) extreme event analysis.</p

Definitiestudie afwegingskader : naar een klimaatbestendig Nederland : definitiestudie Fase 1, kaders voor afweging

Onzekerheid over (omvang en tempo van) de gevolgen van klimaatverandering vormt een essentieel punt bij beslissingen over de ruimtelijke inrichting. De mate waarin en de snelheid waarmee veranderingen optreden zijn niet precies bekend. Een afwegingskader geeft de overheid en de planontwikkelaar instrumenten in handen om de risico’s, de kansen, de kosten en de baten van klimaatadaptatie op verschillende onderscheiden thema’s inzichtelijk te maken. Afwegen: hoe doe je dat. Daarvoor wordt in drie stappen een kader voor gegeven

Genomic Diversity of a Globally Used, Live Attenuated Mycoplasma Vaccine

: The Mycoplasma synoviae live attenuated vaccine strain MS-H (Vaxsafe MS; Bioproperties Pty., Ltd., Australia) is commonly used around the world to prevent chronic infections caused by M. synoviae in birds and to minimize economic losses in the poultry industry. MS-H is a temperature-sensitive strain that is generated via the chemical mutagenesis of a virulent M. synoviae isolate, 86079/7NS. 32 single nucleotide polymorphisms have been found in the genome of MS-H compared to that of 86079/7NS, including 25 in predicted coding sequences (CDSs). There is limited information on the stability of these mutations in MS-H in vitro during the propagation of the vaccine manufacturing process or in vivo after the vaccination of chickens. Here, we performed a comparative analysis of MS-H genomes after in vitro and in vivo passages under different circumstances. Studying the dynamics of the MS-H population can provide insights into the factors that potentially affect the health of vaccinated birds. The genomes of 11 in vitro laboratory passages and 138 MS-H bird reisolates contained a total of 254 sequence variations. Of these, 39 variations associated with CDSs were detected in more than one genome (range = 2 to 62, median = 2.5), suggesting that these sequences are particularly prone to mutations. From the 25 CDSs containing previously characterized variations between MS-H and 86079/7NS, 7 were identified in the MS-H reisolates and progenies examined here. In conclusion, the MS-H genome contains individual regions that are prone to mutations that enable the restoration of the genotype or the phenotype of wild-type 86079/7NS in those regions. However, accumulated mutations in these regions are rare. IMPORTANCE Preventative measures, such as vaccination, are commonly used for the control of mycoplasmal infections in poultry. A live attenuated vaccine strain (Vaxsafe MS; MS-H; Bioproperties Pty. Ltd., Australia) is used for the prevention of disease caused by M. synoviae in many countries. However, information on the stability of previously characterized mutations in the MS-H genome is limited. In this study, we performed a comparative analysis of the whole-genome sequences of MS-H seeds used for vaccine manufacturing, commercial batches of the vaccine, cultures minimally passaged under small-scale laboratory and large-scale manufacturing conditions, MS-H reisolated from specific-pathogen-free (SPF) chickens that were vaccinated under controlled conditions, and MS-H reisolated from vaccinated commercial poultry flocks around the world. This study provides a comprehensive assessment of genome stability in MS-H after in vitro and in vivo passages under different circumstances and suggests that most of the mutations in the attenuated MS-H vaccine strain are stable

The M81 Group Dwarf Irregular Galaxy DDO 165. II. Connecting Recent Star Formation with ISM Structures and Kinematics

We compare the stellar populations and complex neutral gas dynamics of the M81 group dIrr galaxy DDO 165 using data from the HST and the VLA. Paper I identified two kinematically distinct HI components, multiple localized high velocity gas features, and eight HI holes and shells (the largest of which spans ~2.2x1.1 kpc). Using the spatial and temporal information from the stellar populations in DDO 165, we compare the patterns of star formation over the past 500 Myr with the HI dynamics. We extract localized star formation histories within 6 of the 8 HI holes identified in Paper I, as well as 23 other regions that sample a range of stellar densities and neutral gas properties. From population synthesis modeling, we derive the energy outputs (from stellar winds and supernovae) of the stellar populations within these regions over the last 100 Myr, and compare with refined estimates of the energies required to create the HI holes. In all cases, we find that "feedback" is energetically capable of creating the observed structures in the ISM. Numerous regions with significant energy inputs from feedback lack coherent HI structures but show prominent localized high velocity gas features; this feedback signature is a natural product of temporally and spatially distributed star formation. In DDO 165, the extended period of heightened star formation activity (lasting more than 1 Gyr) is energetically capable of creating the observed holes and high velocity gas features in the neutral ISM.Comment: The Astrophysical Journal, in press. Full-resolution version available on request from the first autho

Phase I-II study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell cancer

<p>Abstract</p> <p>Background</p> <p>For patients with metastatic renal cell cancer (mRCC) who progressed on vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor therapy, the orally administered mammalian target of rapamycin (mTOR) inhibitor everolimus has been shown to prolong progression free survival. Intriguingly, inhibition of mTOR also promotes expansion of immunosuppressive regulatory T cells (Tregs) that can inhibit anti-tumor immune responses in a clinically relevant way in various tumor types including RCC. This study intends to investigate whether the antitumor efficacy of everolimus can be increased by preventing the detrimental everolimus induced expansion of Tregs using a metronomic schedule of cyclophosphamide.</p> <p>Methods/design</p> <p>This phase I-II trial is a national multi-center study of different doses and schedules of low-dose oral cyclophosphamide in combination with a fixed dose of everolimus in patients with mRCC not amenable to or progressive after a VEGF-receptor tyrosine kinase inhibitor containing treatment regimen. In the phase I part of the study the optimal Treg-depleting dose and schedule of metronomic oral cyclophosphamide when given in combination with everolimus will be determined. In the phase II part of the study we will evaluate whether the percentage of patients progression free at 4 months of everolimus treatment can be increased from 50% to 70% by adding metronomic cyclophosphamide (in the dose and schedule determined in the phase I part). In addition to efficacy, we will perform extensive immune monitoring with a focus on the number, phenotype and function of Tregs, evaluate the safety and feasibility of the combination of everolimus and cyclophosphamide, perform monitoring of selected angiogenesis parameters and analyze everolimus and cyclophosphamide drug levels.</p> <p>Discussion</p> <p>This phase I-II study is designed to determine whether metronomic cyclophosphamide can be used to counter the mTOR inhibitor everolimus induced Treg expansion in patients with metastatic renal cell carcinoma and increase the antitumor efficacy of everolimus.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT01462214">NCT01462214</a>, EudraCT number 2010-024515-13, Netherlands Trial Register number <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2040">NTR3085</a>.</p

Cyclophosphamide Chemotherapy Sensitizes Tumor Cells to TRAIL-Dependent CD8 T Cell-Mediated Immune Attack Resulting in Suppression of Tumor Growth

Background: Anti-cancer chemotherapy can be simultaneously lymphodepleting and immunostimulatory. Pre-clinical models clearly demonstrate that chemotherapy can synergize with immunotherapy, raising the question how the immune system can be mobilized to generate anti-tumor immune responses in the context of chemotherapy. Methods and Findings: We used a mouse model of malignant mesothelioma, AB1-HA, to investigate T cell-dependent tumor resolution after chemotherapy. Established AB1-HA tumors were cured by a single dose of cyclophosphamide in a CD8 T cell- and NK cell-dependent manner. This treatment was associated with an IFN-α/β response and a profound negative impact on the anti-tumor and total CD8 T cell responses. Despite this negative effect, CD8 T cells were essential for curative responses. The important effector molecules used by the anti-tumor immune response included IFN-γ and TRAIL. The importance of TRAIL was supported by experiments in nude mice where the lack of functional T cells could be compensated by agonistic anti-TRAIL-receptor (DR5) antibodies. Conclusion: The data support a model in which chemotherapy sensitizes tumor cells for T cell-, and possibly NK cell-, mediated apoptosis. A key role of tumor cell sensitization to immune attack is supported by the role of TRAIL in tumor resolution and explains the paradox of successful CD8 T cell-dependent anti-tumor responses in the absence of CD8 T cell expansion

Health and literacy in first- and second-generation Moroccan Berber women in the Netherlands: Ill literacy?

AIM: The present study was aimed at investigating the role of literacy and generation in the self-reported general health status of Moroccan Berber speaking women in the Netherlands. METHOD: Fifty women in our sample (N = 75) were first generation women, from which group 25 were literates and 25 illiterates. Another group of 25 literate women belonged to the second generation. The three groups were matched for demographic characteristics. Questionnaires were administered reflecting all concepts under study. We hypothesized that, within the first generation, illiterates compared with literates would report worse health. Our second hypothesis was that literates of the first generation compared with those of the second generation would have a similar health condition. RESULTS: After controlling for age, having a job, and having an employed partner, the first generation literates compared with the illiterates of the first generation indeed reported significantly better health. Additionally, we did not find any differences in health condition between both literate groups, even after controlling for age, number of children, and marital status. Health complaints that were most frequently reported by both groups, concerned pain in shoulders, back and head. CONCLUSIONS: Our results underline the importance of offering immigrants optimal access to opportunities and facilities that can improve their literacy and reading ability

Measurement of the proton and deuteron structure functions, F2p and F2d, and of the ratio sigma(L)/sigma(T)

The muon-proton and muon-deuteron inclusive deep inelastic scattering cross sections were measured in the kinematic range 0.002 < x < 0.60 and 0.5 < Q2 < 75 GeV2 at incident muon energies of 90, 120, 200 and 280 GeV. These results are based on the full data set collected by the New Muon Collaboration, including the data taken with a small angle trigger. The extracted values of the structure functions F2p and F2d are in good agreement with those from other experiments. The data cover a sufficient range of y to allow the determination of the ratio of the longitudinally to transversely polarised virtual photon absorption cross sections, R= sigma(L)/sigma(T), for 0.002 < x < 0.12 . The values of R are compatible with a perturbative QCD prediction; they agree with earlier measurements and extend to smaller x.Comment: In this replacement the erroneously quoted R values in tables 3-6 for x>0.12, and R1990 values in tables 5-6 for all x, have been corrected, and the cross sections in tables 3-4 have been adapted. Everything else, including the structure functions F2, remained unchanged. 22 pages, LateX, including figures, with two .sty files, and three separate f2tab.tex files for the F2-tables. Accepted for publication in Nucl.Phys.B 199

Stress induced polarization of immune-neuroendocrine phenotypes in Gallus gallus

Immune-neuroendocrine phenotypes (INPs) stand for population subgroups differing in immune-neuroendocrine interactions. While mammalian INPs have been characterized thoroughly in rats and humans, avian INPs were only recently described in Coturnix coturnix (quail). To assess the scope of this biological phenomenon, herein we characterized INPs in Gallus gallus (a domestic hen strain submitted to a very long history of strong selective breeding pressure) and evaluated whether a social chronic stress challenge modulates the individuals’ interplay affecting the INP subsets and distribution. Evaluating plasmatic basal corticosterone, interferon-γ and interleukin-4 concentrations, innate/acquired leukocyte ratio, PHA-P skin-swelling and induced antibody responses, two opposite INP profiles were found: LEWIS-like (15% of the population) and FISCHER-like (16%) hens. After chronic stress, an increment of about 12% in each polarized INP frequency was found at expenses of a reduction in the number of birds with intermediate responses. Results show that polarized INPs are also a phenomenon occurring in hens. The observed inter-individual variation suggest that, even after a considerable selection process, the population is still well prepared to deal with a variety of immune-neuroendocrine challenges. Stress promoted disruptive effects, leading to a more balanced INPs distribution, which represents a new substrate for challenging situations.Fil: Nazar, Franco Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Estevez, Inma. Centro de Investigación. Neiker - Tecnalia; EspañaFil: Correa, Silvia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Marin, Raul Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin