Renewable energy sources have an intermittent character that does not necessarily match energy demand. Such imbalances tend to increase system cost as they require mitigation measures and this is ...undesirable when available resources should be focused on increasing renewable energy supply. Matching supply and demand should therefore be inherent to early stages of system design, to avoid mismatch costs to the greatest extent possible and we need guidelines for that. This paper delivers such guidelines by exploring design of hybrid wind and solar energy and unusual large solar installation angles.
The hybrid wind and solar energy supply and energy demand is studied with an analytical analysis of average monthly energy yields in The Netherlands, Spain and Britain, capacity factor statistics and a dynamic energy supply simulation. The analytical focus in this paper differs from that found in literature, where analyses entirely rely on simulations. Additionally, the seasonal energy yield profile of solar energy at large installation angles is studied with the web application PVGIS and an hourly simulation of the energy yield, based on the Perez model.
In Europe, the energy yield of solar PV peaks during the summer months and the energy yield of wind turbines is highest during the winter months. As a consequence, three basic hybrid supply profiles, based on three different mix ratios of wind to solar PV, can be differentiated: a heating profile with high monthly energy yield during the winter months, a flat or baseload profile and a cooling profile with high monthly energy yield during the summer months. It is shown that the baseload profile in The Netherlands is achieved at a ratio of wind to solar energy yield and power of respectively Ew/Es=1.7 and Pw/Ps=0.6. The baseload ratio for Spain and Britain is comparable because of similar seasonal weather patterns, so that this baseload ratio is likely comparable for other European countries too.
In addition to the seasonal benefits, the hybrid mix is also ideal for the short-term as wind and solar PV adds up to a total that has fewer energy supply flaws and peaks than with each energy source individually and it is shown that they are seldom (3%) both at rated power. This allows them to share one cable, allowing “cable pooling”, with curtailment to -for example-manage cable capacity. A dynamic simulation with the baseload mix supply and a flat demand reveals that a 100% and 75% yearly energy match cause a curtailment loss of respectively 6% and 1%. Curtailment losses of the baseload mix are thereby shown to be small.
Tuning of the energy supply of solar panels separately is also possible. Compared to standard 40° slope in The Netherlands, facade panels have smaller yield during the summer months, but almost equal yield during the rest of the year, so that the total yield adds up to 72% of standard 40° slope panels. Additionally, an hourly energy yield simulation reveals that: façade (90°) and 60° slope panels with an inverter rated at respectively 50% and 65% Wp, produce 95% of the maximum energy yield at that slope. The flatter seasonal yield profile of “large slope panels” together with decreased peak power fits Dutch demand and grid capacity more effectively.
We study the effects of fiscal policy interventions in a liquidity trap in a model with nominal rigidities and an interest rate rule. In a liquidity trap caused by a self-fulfilling state of low ...confidence, higher government spending has deflationary effects that reduce the spending multiplier when the zero lower bound is binding. Instead, cuts in marginal labour tax rates are inflationary and become more expansionary when the zero lower bound is binding. These findings contradict a popular view, based on a liquidity trap caused by a fundamental shock such as a taste shock, that higher government spending is inflationary and can therefore be associated with large multipliers at the zero lower bound, while lower marginal tax rates are deflationary and therefore counterproductive.
In this contribution, we review the status and perspectives of direct neutrino mass experiments, which investigate the kinematics of β-decays of specific isotopes (3H, 187Re, 163Ho) to derive ...model-independent information on the averaged electron (anti)neutrino mass. After discussing the kinematics of β-decay and the determination of the neutrino mass, we give a brief overview of past neutrino mass measurements (SN1987a-ToF studies, Mainz and Troitsk experiments for 3H, cryobolometers for 187Re). We then describe the Karlsruhe Tritium Neutrino (KATRIN) experiment currently under construction at Karlsruhe Institute of Technology, which will use the MAC-E-Filter principle to push the sensitivity down to a value of 200 meV (90% C.L.). To do so, many technological challenges have to be solved related to source intensity and stability, as well as precision energy analysis and low background rate close to the kinematic endpoint of tritium β-decay at 18.6 keV. We then review new approaches such as the MARE, ECHO, and Project8 experiments, which offer the promise to perform an independent measurement of the neutrino mass in the sub-eV region. Altogether, the novel methods developed in direct neutrino mass experiments will provide vital information on the absolute mass scale of neutrinos.
Fibroblast growth factor receptor 3 (FGFR3) is an actionable target in bladder cancer (BC). FGFR3 mutations are common in noninvasive BC and associated with favorable BC prognosis. Overexpression was ...reported in up to 40% of FGFR3 wild-type muscle-invasive BC. We analyzed FGFR3 mutations, FGFR3, and p53 protein expression and assessed their prognostic value in a cohort of 1000 chemotherapy-naive radical cystectomy specimens. FGFR3 mutations were found in 11%, FGFR3 overexpression was found in 28%, and p53 overexpression was found in 69% of tumors. Among FGFR3 mutant tumors, 73% had FGFR3 overexpression versus 22% among FGFR3 wild-type tumors. FGFR3 mutations were significantly associated with lower pT stage, tumor grade, absence of carcinoma in situ, pN0, low-level p53, and longer disease-specific survival (DSS). FGFR3 overexpression was associated only with lower pT stage and tumor grade. Moreover, FGFR3 overexpression was not associated with DSS in patients with FGFR3 wild-type tumors. In conclusion, FGFR3 mutations identified patients with favorable BC at cystectomy. Our results suggest that FGFR3 mutations have a driver role and are functionally distinct from FGFR3 overexpression. Hence, patients with FGFR3 mutations would be more likely to benefit from anti-FGFR3 therapy. Ideally, further research is needed to test this hypothesis.
Oncogenic fibroblast growth factor receptor 3 (FGFR3) mutations are very common in bladder cancer. In this report, we found that these FGFR3 mutations were associated with favorable features and prognosis of bladder cancer compared with patients with FGFR3 overexpressed tumors only. As a consequence, patients with FGFR3 mutant tumors would be more likely to benefit from anti-FGFR3 therapy than patients with FGFR3 protein overexpression only.
Oncogenic fibroblast growth factor receptor 3 (FGFR3) mutations were associated with favorable bladder cancer in a series of 1000 radical cystectomy cases. Moreover, patients with FGFR3 mutant tumors would be more likely to benefit from anti-FGFR3 therapy than patients with overexpression only.
Morphea and Eosinophilic Fasciitis: An Update Mertens, Jorre S.; Seyger, Marieke M. B.; Thurlings, Rogier M. ...
American journal of clinical dermatology,
08/2017, Letnik:
18, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Morphea, also known as localized scleroderma, encompasses a group of idiopathic sclerotic skin diseases. The spectrum ranges from relatively mild phenotypes, which generally cause few problems ...besides local discomfort and visible disfigurement, to subtypes with severe complications such as joint contractures and limb length discrepancies. Eosinophilic fasciitis (EF, Shulman syndrome) is often regarded as belonging to the severe end of the morphea spectrum. The exact driving mechanisms behind morphea and EF pathogenesis remain to be elucidated. However, extensive extracellular matrix formation and autoimmune dysfunction are thought to be key pathogenic processes. Likewise, these processes are considered essential in systemic sclerosis (SSc) pathogenesis. In addition, similarities in clinical presentation between morphea and SSc have led to many theories about their relatedness. Importantly, morphea may be differentiated from SSc based on absence of sclerodactyly, Raynaud’s phenomenon, and nailfold capillary changes. The diagnosis of morphea is often based on characteristic clinical findings. Histopathological evaluation of skin biopsies and laboratory tests are not necessary in the majority of morphea cases. However, full-thickness skin biopsies, containing fascia and muscle tissue, are required for the diagnosis of EF. Monitoring of disease activity and damage, especially of subcutaneous involvement, is one of the most challenging aspects of morphea care. Therefore, data harmonization is crucial for optimizing standard care and for comparability of study results. Recently, the localized scleroderma cutaneous assessment tool (LoSCAT) has been developed and validated for morphea. The LoSCAT is currently the most widely reported outcome measure for morphea. Care providers should take disease subtype, degree of activity, depth of involvement, and quality-of-life impairments into account when initiating treatment. In most patients with circumscribed superficial subtypes, treatment with topical therapies suffices. In more widespread disease, UVA1 phototherapy or systemic treatment with methotrexate (MTX), with or without a systemic corticosteroid combination, should be initiated. Disappointingly, few alternatives for MTX have been described and additional research is still needed to optimize treatment for these debilitating conditions. In this review, we present a state-of-the-art flow chart that guides care providers in the treatment of morphea and EF.
The interferon (IFN) signature is related to disease activity and vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and represents a promising therapeutic ...target. Quantification of the IFN signature is currently performed by gene expression analysis, limiting its current applicability in clinical practice. Therefore, the objective of this study was to establish an easy to measure biomarker for the IFN signature.
Serum levels of galectin-9, CXCL-10 (IP-10) and tumour necrosis factor receptor type II (TNF-RII) were measured in patients with SLE, SLE+APS and primary APS (PAPS) and healthy controls (n=148) after an initial screening of serum analytes in a smaller cohort (n=43). Analytes were correlated to measures of disease activity and the IFN signature. The performance of galectin-9, CXCL-10 and TNF-RII as biomarkers to detect the IFN signature was assessed by receiver operating characteristic curves.
Galectin-9, CXCL-10 and TNF-RII were elevated in patients with SLE, SLE+APS and PAPS (p<0.05) and correlated with disease activity and tissue factor expression. Galectin-9 correlated stronger than CXCL-10 or TNF-RII with the IFN score (r=0.70, p<0.001) and was superior to CXCL-10 or TNF-RII in detecting the IFN signature (area under the curve (AUC) 0.86). Importantly, in patients with SLE(±APS), galectin-9 was also superior to anti-dsDNA antibody (AUC 0.70), or complement C3 (AUC 0.70) and C4 (AUC 0.78) levels in detecting the IFN signature.
Galectin-9 is a novel, easy to measure hence clinically applicable biomarker to detect the IFN signature in patients with systemic autoimmune diseases such as SLE and APS.
We investigate the Gilbert damping and the magnetization switching of perpendicularly magnetized FeCoB-based free layers (FLs) embedded in magnetic tunnel junctions adequate for spin-torque-operated ...magnetic memories. We first study the influence of the boron content in MgO/FeCoB/Ta systems alloys on their Gilbert damping parameter after crystallization annealing. Increasing the boron content from 20% to 30% increases the crystallization temperature, thereby postponing the onset of elemental diffusion within the FL. This reduction of the interdiffusion of the Ta atoms helps maintaining the Gilbert damping at a low level of 0.009 without any penalty on the anisotropy and the magnetotransport properties up to the 400 °C annealing required in CMOS back-end-of-line processing. In addition, we show that dual MgO FLs of composition MgO/FeCoB/Ta/FeCoB/MgO have a substantially lower damping than their MgO/FeCoB/Ta counterparts, reaching damping parameters as low as 0.0039 for a 3 Å thick tantalum spacer. This confirms that the dominant channel of damping is the presence of Ta impurities within the FeCoB alloy. On optimized tunnel junctions, we then study the duration of the switching events induced by spin-transfer torque. We focus on the sub-threshold thermally activated switching in optimal applied field conditions. From the electrical signatures of the switching, we infer that once the nucleation has occurred, the reversal proceeds by a domain wall (DW) sweeping though the device at a few 10 m/s. The smaller the device, the faster its switching. We present an analytical model to account for our findings. The DW velocity is predicted to scale linearly with the current for devices much larger than the wall width. The wall velocity depends on the Bloch DW width, such that the devices with the lowest exchange stiffness will be the ones that host the DWs with the slowest mobilities.
Objective
Objective evaluation of disease activity is challenging in patients with juvenile dermatomyositis (DM) due to a lack of reliable biomarkers, but it is crucial to avoid both under‐ and ...overtreatment of patients. Recently, we identified 2 proteins, galectin‐9 and CXCL10, whose levels are highly correlated with the extent of juvenile DM disease activity. This study was undertaken to validate galectin‐9 and CXCL10 as biomarkers for disease activity in juvenile DM, and to assess their disease specificity and potency in predicting the occurrence of flares.
Methods
Levels of galectin‐9 and CXCL10 were measured by multiplex immunoassay in serum samples from 125 unique patients with juvenile DM in 3 international cross‐sectional cohorts and a local longitudinal cohort. The disease specificity of both proteins was examined in 50 adult patients with DM or nonspecific myositis (NSM) and 61 patients with other systemic autoimmune diseases.
Results
Both cross‐sectionally and longitudinally, galectin‐9 and CXCL10 outperformed the currently used laboratory marker, creatine kinase (CK), in distinguishing between juvenile DM patients with active disease and those in remission (area under the receiver operating characteristic curve AUC 0.86–0.90 for galectin‐9 and CXCL10; AUC 0.66–0.68 for CK). The sensitivity and specificity for active disease in juvenile DM was 0.84 and 0.92, respectively, for galectin‐9 and 0.87 and 1.00, respectively, for CXCL10. In 10 patients with juvenile DM who experienced a flare and were prospectively followed up, continuously elevated or rising biomarker levels suggested an imminent flare up to several months before the onset of symptoms, even in the absence of elevated CK levels. Galectin‐9 and CXCL10 distinguished between active disease and remission in adult patients with DM or NSM (P = 0.0126 for galectin‐9 and P < 0.0001 for CXCL10) and were suited for measurement in minimally invasive dried blood spots (healthy controls versus juvenile DM, P = 0.0040 for galectin‐9 and P < 0.0001 for CXCL10).
Conclusion
In this study, galectin‐9 and CXCL10 were validated as sensitive and reliable biomarkers for disease activity in juvenile DM. Implementation of these biomarkers into clinical practice as tools to monitor disease activity and guide treatment might facilitate personalized treatment strategies.
Understanding of the colloidal interactions of Norovirus particles in aqueous medium could provide insights on the origins of the notorious stability and infectivity of these widespread viral agents. ...We characterized the effects of solution pH and surfactant type and concentration on the aggregation, dispersion, and disassembly of Norovirus virus-like particles (VLPs) using dynamic light scattering, electrophoretic light scattering, and transmission electron microscopy. Owing to net negative surface charge of the VLPs at neutral pH, low concentrations of cationic surfactant tend to aggregate the VLPs, whereas low concentrations of anionic surfactant tend to disperse the particles. Increasing the concentration of these surfactants beyond their critical micelle concentration leads to virus capsid disassembly and breakdown of aggregates. Non-ionic surfactants, however, had little effect on virus interactions and likely stabilized them additionally in suspension. The data were interpreted on the basis of simple models for surfactant binding and re-charging of the virus capsid. We used zeta potential data to characterize virus surface charge and interpret the mechanisms behind these demonstrated surfactant-virus interactions. The fundamental understanding and control of these interactions will aid in practical formulations for virus inactivation and removal from contaminated surfaces.
Two experiments in two seasons evaluated fertilization rate and embryonic development in dairy cattle. Experiment 1 (summer) compared lactating Holstein cows (n = 27; 97.3±4.1 d postpartum dpp; ...40.0±1.5kg milk/d) to nulliparous heifers (n = 28; 11 to 17 mo old). Experiment 2 (winter) compared lactating cows (n = 27; 46.4±1.6 dpp; 45.9±1.4kg milk/d) to dry cows (n = 26). Inseminations based on estrus included combined semen from four high-fertility bulls. Embryos and oocytes recovered 5 d after ovulation were evaluated for fertilization, embryo quality (1 = excellent to 5 = degenerate), nuclei/embryo, and accessory sperm. In experiment 1, 21 embryos and 17 unfertilized oocytes (UFO) were recovered from lactating cows versus 32 embryos and no UFO from heifers (55% vs. 100% fertilization). Embryos from lactating cows had inferior quality scores (3.8±0.4 vs. 2.2±0.3), fewer nuclei/embryo (19.3±3.7 vs. 36.8±3.0) but more accessory sperm (37.3±5.8 vs. 22.4±5.5/embryo) than embryos from heifers. Sperm were attached to 80% of UFO (17.8±12.1 sperm/UFO). In experiment 2, lactating cows yielded 36 embryos and 5 UFO versus 34 embryos and 4 UFO from dry cows (87.8 vs. 89.5% fertilization). Embryo quality from lactating cows was inferior to dry cows (3.1±0.3 vs. 2.2±0.3), but embryos had similar numbers of nuclei (27.2±2.7 vs. 30.6±2.1) and accessory sperm (42.0±9.4 vs. 36.5±6.3). From 53% of the flushings from lactating cows and 28% from dry cows, only nonviable embryos were collected. Thus, embryos of lactating dairy cows were detectably inferior to embryos from nonlactating females as early as 5 d after ovulation, with a surprisingly high percentage of nonviable embryos. In addition, fertilization rate was reduced only in summer, apparently due to an effect of heat stress on the oocyte.
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