Simulation of hypoxia PET-tracer uptake in tumours:Dependence of clinical uptake-values on transport parameters and arterial input function

Poor radiotherapy outcome is in many cases related to hypoxia, due to the increased radioresistance of hypoxic tumour cells. Positron emission tomography may be used to non-invasively assess the oxygenation status of the tumour using hypoxia-specific radiotracers. Quantification and interpretation of these images remains challenging, since radiotracer binding and oxygen tension are not uniquely related. Computer simulation is a useful tool to improve the understanding of tracer dynamics and its relation to clinical uptake parameters currently used to quantify hypoxia. In this study, a model for simulating oxygen and radiotracer distribution in tumours was implemented to analyse the impact of physiological transport parameters and of the arterial input function (AIF) on: oxygenation histograms, time-activity curves, tracer binding and clinical uptake-values (tissue-to-blood ratio, TBR, and a composed hypoxia-perfusion metric, FHP). Results were obtained for parallel and orthogonal vessel architectures and for vascular fractions (VFs) of 1% and 3%. The most sensitive parameters were the AIF and the maximum binding rate (K-max). TBR allowed discriminating VF for different AIF, and FHP for different K-max, but neither TBR nor FHP were unbiased in all cases. Biases may especially occur in the comparison of TBR- or FHP-values between different tumours, where the relation between measured and actual AIF may vary. Thus, these parameters represent only surrogates rather than absolute measurements of hypoxia in tumours.Pontificia Universidad Catolica de Chile (UC) from the German Academic Exchange Service (DAAD) German Cancer Research Center (DKFZ) from the German Academic Exchange Service (DAAD) grant CONICYT Doctorado Nacional 21151353 Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 111505601 1117057

Late normal tissue response in the rat spinal cord after carbon ion irradiation

Background: The present work summarizes the research activities on radiation-induced late effects in the rat spinal cord carried out within the “clinical research group ion beam therapy” funded by the German Research Foundation (DFG, KFO 214). Methods and materials: Dose–response curves for the endpoint radiation-induced myelopathy were determined at 6 different positions (LET 16–99 keV/μm) within a 6 cm spread-out Bragg peak using either 1, 2 or 6 fractions of carbon ions. Based on the tolerance dose TD50 of carbon ions and photons, the relative biological effectiveness (RBE) was determined and compared with predictions of the local effect model (LEM I and IV). Within a longitudinal magnetic resonance imaging (MRI)-based study the temporal development of radiation-induced changes in the spinal cord was characterized. To test the protective potential of the ACE (angiotensin converting enzyme)-inhibitor ramipril™, an additional dose–response experiment was performed. Results: The RBE-values increased with LET and the increase was found to be larger for smaller fractional doses. Benchmarking the RBE-values as predicted by LEM I and LEM IV with the measured data revealed that LEM IV is more accurate in the high-LET, while LEM I is more accurate in the low-LET region. Characterization of the temporal development of radiation-induced changes with MRI demonstrated a shorter latency time for carbon ions, reflected on the histological level by an increased vessel perforation after carbon ion as compared to photon irradiations. For the ACE-inhibitor ramipril™, a mitigative rather than protective effect was found. Conclusions: This comprehensive study established a large and consistent RBE data base for late effects in the rat spinal cord after carbon ion irradiation which will be further extended in ongoing studies. Using MRI, an extensive characterization of the temporal development of radiation-induced alterations was obtained. The reduced latency time for carbon ions is expected to originate from a dynamic interaction of various complex pathological processes. A dominant observation after carbon ion irradiation was an increase in vessel perforation preferentially in the white matter. To enable a targeted pharmacological intervention more details of the molecular pathways, responsible for the development of radiation-induced myelopathy are required

Multi‐Electron Reactions enabled by Anion‐Based Redox Chemistry for High‐Energy Multivalent Rechargeable Batteries

The development of multivalent metal (such as Mg and Ca) based battery systems is hindered by lack of suitable cathode chemistry that shows reversible multi‐electron redox reactions. Cationic redox centres in the classical cathodes can only afford stepwise single‐electron transfer, which are not ideal for multivalent‐ion storage. The charge imbalance during multivalent ion insertion might lead to an additional kinetic barrier for ion mobility. Therefore, multivalent battery cathodes only exhibit slope‐like voltage profiles with insertion/extraction redox of less than one electron. Taking VS4 as a model material, reversible two‐electron redox with cationic–anionic contributions is verified in both rechargeable Mg batteries (RMBs) and rechargeable Ca batteries (RCBs). The corresponding cells exhibit high capacities of >300 mAh g−1 at a current density of 100 mA g−1 in both RMBs and RCBs, resulting in a high energy density of >300 Wh kg−1 for RMBs and >500 Wh kg−1 for RCBs. Mechanistic studies reveal a unique redox activity mainly at anionic sulfides moieties and fast Mg2+ ion diffusion kinetics enabled by the soft structure and flexible electron configuration of VS4

Global Analysis of Circulating Immune Cells by Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry

Background: MALDI-TOF mass spectrometry is currently used in microbiological diagnosis to characterize bacterial populations. Our aim was to determine whether this technique could be applied to intact eukaryotic cells, and in particular, to cells involved in the immune response. Methodology/Principal Findings: A comparison of frozen monocytes, T lymphocytes and polymorphonuclear leukocytes revealed specific peak profiles. We also found that twenty cell types had specific profiles, permitting the establishment of a cell database. The circulating immune cells, namely monocytes, T lymphocytes and polymorphonuclear cells, were distinct from tissue immune cells such as monocyte-derived macrophages and dendritic cells. In addition, MALDI-TOF mass spectrometry was valuable to easily identify the signatures of monocytes and T lymphocytes in peripheral mononuclear cells. Conclusions/Significance: This method was rapid and easy to perform, and unlike flow cytometry, it did not require any additional components such as specific antibodies. The MALDI-TOF mass spectrometry approach could be extended t

Vegetation type is an important predictor of the arctic summer land surface energy budget

Despite the importance of high-latitude surface energy budgets (SEBs) for land-climate interactions in the rapidly changing Arctic, uncertainties in their prediction persist. Here, we harmonize SEB observations across a network of vegetated and glaciated sites at circumpolar scale (1994-2021). Our variance-partitioning analysis identifies vegetation type as an important predictor for SEB-components during Arctic summer (June-August), compared to other SEB-drivers including climate, latitude and permafrost characteristics. Differences among vegetation types can be of similar magnitude as between vegetation and glacier surfaces and are especially high for summer sensible and latent heat fluxes. The timing of SEB-flux summer-regimes (when daily mean values exceed 0 Wm(-2)) relative to snow-free and -onset dates varies substantially depending on vegetation type, implying vegetation controls on snow-cover and SEB-flux seasonality. Our results indicate complex shifts in surface energy fluxes with land-cover transitions and a lengthening summer season, and highlight the potential for improving future Earth system models via a refined representation of Arctic vegetation types.An international team of researchers finds high potential for improving climate projections by a more comprehensive treatment of largely ignored Arctic vegetation types, underscoring the importance of Arctic energy exchange measuring stations.Peer reviewe

The relationship between niche breadth and range size of beech (Fagus) species worldwide

Aim: This work explores whether the commonly observed positive range size–niche breadth relationship exists for Fagus, one of the most dominant and widespread broad-leaved deciduous tree genera in temperate forests of the Northern Hemisphere. Additionally, we ask whether the 10 extant Fagus species’ niche breadths and climatic tolerances are under phylogenetic control. Location: Northern Hemisphere temperate forests. Taxon: Fagus L. Methods: Combining the global vegetation database sPlot with Chinese vegetation data, we extracted 107,758 relevés containing Fagus species. We estimated biotic and climatic niche breadths per species using plot-based co-occurrence data and a resource-based approach, respectively. We examined the relationships of these estimates with range size and tested for their phylogenetic signal, prior to which a Random Forest (RF) analysis was applied to test which climatic properties are most conserved across the Fagus species. Results: Neither biotic niche breadth nor climatic niche breadth was correlated with range size, and the two niche breadths were incongruent as well. Notably, the widespread North American F. grandifolia had a distinctly smaller biotic niche breadth than the Chinese Fagus species (F. engleriana, F. hayatae, F. longipetiolata and F. lucida) with restricted distributions in isolated mountains. The RF analysis revealed that cold tolerance did not differ among the 10 species, and thus may represent an ancestral, fixed trait. In addition, neither biotic nor climatic niche breadths are under phylogenetic control. Main Conclusions: We interpret the lack of a general positive range size–niche breadth relationship within the genus Fagus as a result of the widespread distribution, high among-region variation in available niche space, landscape heterogeneity and Quaternary history. The results hold when estimating niche sizes either by fine-scale co-occurrence data or coarse-scale climate data, suggesting a mechanistic link between factors operating across spatial scales. Besides, there was no evidence for diverging ecological specialization within the genus Fagus

Vegetation type is an important predictor of the arctic summer land surface energy budget

Despite the importance of high-latitude surface energy budgets (SEBs) for land-climate interactions in the rapidly changing Arctic, uncertainties in their prediction persist. Here, we harmonize SEB observations across a network of vegetated and glaciated sites at circumpolar scale (1994–2021). Our variance-partitioning analysis identifies vegetation type as an important predictor for SEB-components during Arctic summer (June-August), compared to other SEB-drivers including climate, latitude and permafrost characteristics. Differences among vegetation types can be of similar magnitude as between vegetation and glacier surfaces and are especially high for summer sensible and latent heat fluxes. The timing of SEB-flux summer-regimes (when daily mean values exceed 0 Wm−2) relative to snow-free and -onset dates varies substantially depending on vegetation type, implying vegetation controls on snow-cover and SEB-flux seasonality. Our results indicate complex shifts in surface energy fluxes with land-cover transitions and a lengthening summer season, and highlight the potential for improving future Earth system models via a refined representation of Arctic vegetation types

Scenario set-up and forcing data for impact model evaluation and impact attribution within the third round of the Inter-Sectoral Model Intercomparison Project (ISIMIP3a)

This paper describes the rationale and the protocol of the first component of the third simulation round of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP3a, www.isimip.org) and the associated set of climate-related and direct human forcing data (CRF and DHF, respectively). The observation-based climate-related forcings for the first time include high-resolution observational climate forcings derived by orographic downscaling, monthly to hourly coastal water levels, and wind fields associated with historical tropical cyclones. The DHFs include land use patterns, population densities, information about water and agricultural management, and fishing intensities. The ISIMIP3a impact model simulations driven by these observation-based climate-related and direct human forcings are designed to test to what degree the impact models can explain observed changes in natural and human systems. In a second set of ISIMIP3a experiments the participating impact models are forced by the same DHFs but a counterfactual set of atmospheric forcings and coastal water levels where observed trends have been removed. These experiments are designed to allow for the attribution of observed changes in natural, human and managed systems to climate change, rising CH4 and CO2 concentrations, and sea level rise according to the definition of the Working Group II contribution to the IPCC AR6