bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial Covariance Modeling for Stochastic Subgrid‐Scale Parameterizations Using Dynamic Mode Decomposition
Authors: Gugole Federica , Franzke Christian L. E. 
Published: June 2020

AbstractStochastic parameterizations are increasingly being used in climate modeling to represent subgrid‐scale processes. While different parameterizations are being developed considering different aspects of the physical phenomena, less attention is given to technical and numerical aspects. In particular, empirical orthogonal functions (EOFs) are employed when a spatial structure is required. Here, we provide evidence they might not be the most suitable choice. By applying an energy‐consistent parameterization to the two‐layer quasi‐geostrophic (QG) model, we investigate the model sensitivity to a priori assumptions made on the parameterization. In particular, we consider here two methods to prescribe the spatial covariance of the noise: first, by using climatological variability patterns provided by EOFs, and second, by using time‐varying dynamics‐adapted Koopman modes, approximated by dynamic mode decomposition (DMD). The performance of the two methods are analyzed through numerical simulations of the stochastic system on a coarse spatial resolution and the outcomes compared to a high‐resolution simulation of the original deterministic system. The comparison reveals that the DMD‐based noise covariance scheme outperforms the EOF‐based one. The use of EOFs leads to a significant increase of the ensemble spread and to a meridional misplacement of the bimodal eddy kinetic energy (EKE) distribution. Conversely, using DMDs, the ensemble spread is confined, the meridional propagation of the zonal jet stream is accurately captured, and the total variance of the system is improved. Our results highlight the importance of the systematic design of stochastic parameterizations with dynamically adapted spatial correlations, rather than relying on statistical spatial patterns.
The Role of Isotope‐Enabled GCM Complexity in Simulating Tropical Circulation Changes in High‐CO2 Scenarios
Authors: Hu Jun , Dee Sylvia , Nusbaumer Jesse 
Published: June 2020

AbstractStable water isotopes are data‐rich tracers of the hydrological cycle, and, recently, the advent of isotope‐enabled climate models has allowed for investigations into the utility of water isotopes for tracking changes in the large‐scale atmospheric circulation. Among the suite of published isotope‐enabled climate models, those with intermediate complexity offer the benefits of efficiency, allowing for long ensemble runs. However, the ability of these models to simulate the response to global warming with the same fidelity as state‐of‐the‐art models is questionable. Here we evaluate an intermediate complexity model, SPEEDY‐IER, in a high‐CO2 scenario and compare its performance to an Intergovernmental Panel on Climate Change (IPCC)‐class model, iCAM5. SPEEDY‐IER can generally simulate changes in tropical circulation, the weakening of the Walker circulation, and the narrowing of the deep tropics. A deeper investigation of water isotope fields indicates SPEEDY‐IER simulates qualitative trends in precipitation and vapor isotopes with fidelity, but it does not simulate amplitudes or spatial patterns of water isotope changes shown in iCAM5. This bias in SPEEDY‐IER is mainly due to its coarse resolution and simplified convection scheme. We then modify the model by introducing condensation and detrainment in intermediate convection levels; this modification successfully improves SPEEDY‐IER's simulation of water isotope fields, though the response of the Walker circulation to climate change is weakened. We demonstrate that evaluating water isotope fields reveals hidden biases in a climate model and guides improvements to the model's performance. Thus, the examination of water isotope fields and validation against available observations likely provides more stringent constraints for model physics.
Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification—an approach to classification of patients with t-MDS
Authors: Kuendgen A. , Nomdedeu M. , Tuechler H. , Garcia-Manero G. , Komrokji R. S. , Sekeres M. A. , Della Porta M. G. , Cazzola M. , DeZern A. E. , Roboz G. J. , Steensma D. P. , Van de Loosdrecht A. A. , Schlenk R. F. , Grau J. , Calvo X. , Blum S. , Pereira A. , Valent P. , Costa D. , Giagounidis A. , Xicoy B. , Döhner H. , Platzbecker U. , Pedro C. , Lübbert M. , Oiartzabal I. , Díez-Campelo M. , Cedena M. T. , Machherndl-Spandl S. , López-Pavía M. , Baldus C. D. , Martinez-de-Sola M. , Stauder R. , Merchan B. , List A. , Ganster C. , Schroeder T. , Voso M. T. , Pfeilstöcker M. , Sill H. , Hildebrandt B. , Esteve J. , Nomdedeu B. , Cobo F. , Haas R. , Sole F. , Germing U. , Greenberg P. L. , Haase D. , Sanz G. 
Published: June 2020

AbstractIn the current World Health Organization (WHO)-classification, therapy-related myelodysplastic syndromes (t-MDS) are categorized together with therapy-related acute myeloid leukemia (AML) and t-myelodysplastic/myeloproliferative neoplasms into one subgroup independent of morphologic or prognostic features. Analyzing data of 2087 t-MDS patients from different international MDS groups to evaluate classification and prognostication tools we found that applying the WHO classification for p-MDS successfully predicts time to transformation and survival (both p < 0.001). The results regarding carefully reviewed cytogenetic data, classifications, and prognostic scores confirmed that t-MDS are similarly heterogeneous as p-MDS and therefore deserve the same careful differentiation regarding risk. As reference, these results were compared with 4593 primary MDS (p-MDS) patients represented in the International Working Group for Prognosis in MDS database (IWG-PM). Although a less favorable clinical outcome occurred in each t-MDS subset compared with p-MDS subgroups, FAB and WHO-classification, IPSS-R, and WPSS-R separated t-MDS patients into differing risk groups effectively, indicating that all established risk factors for p-MDS maintained relevance in t-MDS, with cytogenetic features having enhanced predictive power. These data strongly argue to classify t-MDS as a separate entity distinct from other WHO-classified t-myeloid neoplasms, which would enhance treatment decisions and facilitate the inclusion of t-MDS patients into clinical studies.
Tailored elastic surface to body wave Umklapp conversion
Authors: Chaplain Gregory J. , De Ponti Jacopo M. , Colombi Andrea , Fuentes-Dominguez Rafael , Dryburg Paul , Pieris Don , Smith Richard J. , Clare Adam , Clark Matt , Craster Richard V. 
Published: June 2020

AbstractElastic waves guided along surfaces dominate applications in geophysics, ultrasonic inspection, mechanical vibration, and surface acoustic wave devices; precise manipulation of surface Rayleigh waves and their coupling with polarised body waves presents a challenge that offers to unlock the flexibility in wave transport required for efficient energy harvesting and vibration mitigation devices. We design elastic metasurfaces, consisting of a graded array of rod resonators attached to an elastic substrate that, together with critical insight from Umklapp scattering in phonon-electron systems, allow us to leverage the transfer of crystal momentum; we mode-convert Rayleigh surface waves into bulk waves that form tunable beams. Experiments, theory and simulation verify that these tailored Umklapp mechanisms play a key role in coupling surface Rayleigh waves to reversed bulk shear and compressional waves independently, thereby creating passive self-phased arrays allowing for tunable redirection and wave focusing within the bulk medium.
Long-term culture of human pancreatic slices as a model to study real-time islet regeneration
Authors: Qadir Mirza Muhammad Fahd , Álvarez-Cubela Silvia , Weitz Jonathan , Panzer Julia K. , Klein Dagmar , Moreno-Hernández Yaisa , Cechin Sirlene , Tamayo Alejandro , Almaça Joana , Hiller Helmut , Beery Maria , Kusmartseva Irina , Atkinson Mark , Speier Stephan , Ricordi Camillo , Pugliese Alberto , Caicedo Alejandro , Fraker Christopher A. , Pastori Ricardo Luis , Domínguez-Bendala Juan 
Published: June 2020

AbstractThe culture of live pancreatic tissue slices is a powerful tool for the interrogation of physiology and pathology in an in vitro setting that retains near-intact cytoarchitecture. However, current culture conditions for human pancreatic slices (HPSs) have only been tested for short-term applications, which are not permissive for the long-term, longitudinal study of pancreatic endocrine regeneration. Using a culture system designed to mimic the physiological oxygenation of the pancreas, we demonstrate high viability and preserved endocrine and exocrine function in HPS for at least 10 days after sectioning. This extended lifespan allowed us to dynamically lineage trace and quantify the formation of insulin-producing cells in HPS from both non-diabetic and type 2 diabetic donors. This technology is expected to be of great impact for the conduct of real-time regeneration/developmental studies in the human pancreas.
Hybrid Modelling of Transarterial Chemoembolisation Therapies (TACE) for Hepatocellular Carcinoma (HCC)
Authors: Perfahl H. , Jain H. V. , Joshi T. , Horger M. , Malek N. , Bitzer M. , Reuss M. 
Published: June 2020

AbstractWe extend an agent-based multiscale model of vascular tumour growth and angiogenesis to describe transarterial chemoembolisation (TACE) therapies. The model accounts for tumour and normal cells that are both nested in a vascular system that changes its structure according to tumour-related growth factors. Oxygen promotes nutrients to the tissue and determines cell proliferation or death rates. Within the extended model TACE is included as a two-step process: First, the purely mechanical influence of the embolisation therapy is modelled by a local occlusion of the tumour vasculature. There we distinguish between partial and complete responders, where parts of the vascular system are occluded for the first and the whole tumour vasculature is destroyed for the latter. In the second part of the model, drug eluding beads (DEBs) carrying the chemotherapeutic drug doxorubicin are located at destroyed vascular locations, releasing the drug over a certain time-window. Simulation results are parameterised to qualitatively reproduce clinical observations. Patients that undergo a TACE-treatment are categorised in partial and complete responders one day after the treatment. Another 90 days later reoccurance or complete response are detected by volume perfusion computer tomography (VPCT). Our simulations reveal that directly after a TACE- treatment an unstable tumour state can be observed, where regrowth and total tumour death have the same likeliness. It is argued that this short time-window is favorable for another therapeutical intervention with a less radical therapy. This procedure can shift the outcome to more effectiveness. Simulation results with an oxygen therapy within the unstable time-window demonstrate a potentially positive manipulated outcome. Finally, we conclude that our TACE model can motivate new therapeutical strategies and help clinicians analyse the intertwined relations and cross-links in tumours.
Protonic Capacitor: Elucidating the biological significance of mitochondrial cristae formation
Authors: Lee James Weifu 
Published: June 2020

AbstractFor decades, it was not entirely clear why mitochondria develop cristae? The work employing the transmembrane-electrostatic proton localization theory reported here has now provided a clear answer to this fundamental question. Surprisingly, the transmembrane-electrostatically localized proton concentration at a curved mitochondrial crista tip can be significantly higher than that at the relatively flat membrane plane regions where the proton-pumping respiratory supercomplexes are situated. The biological significance for mitochondrial cristae has now, for the first time, been elucidated at a protonic bioenergetics level: 1) The formation of cristae creates more mitochondrial inner membrane surface area and thus more protonic capacitance for transmembrane-electrostatically localized proton energy storage; and 2) The geometric effect of a mitochondrial crista enhances the transmembrane-electrostatically localized proton density to the crista tip where the ATP synthase can readily utilize the localized proton density to drive ATP synthesis.
Utility-scale solar PV performance enhancements through system-level modifications
Authors: Glick Andrew , Ali Naseem , Bossuyt Juliaan , Calaf Marc , Cal Raúl Bayoán 
Published: June 2020

AbstractPerformance of solar PV diminishes with the increase in temperature of the solar modules. Therefore, to further facilitate the reduction in cost of photovoltaic energy, new approaches to limit module temperature increase in natural ambient conditions should be explored. Thus far only approaches based at the individual panel level have been investigated, while the more complex, systems approach remains unexplored. Here, we perform the first wind tunnel scaled solar farm experiments to investigate the potential for temperature reduction through system-level flow enhancement. The percentage of solar irradiance converted into electric power depends upon module efficiency, typically less than 20%. The remaining 80% of solar irradiance is converted into heat, and thus improved heat removal becomes an important factor in increasing performance. Here, We investigate the impact of module inclination on system-level flow and the convective heat transfer coefficient. Results indicate that significant changes in the convective heat transfer coefficient are possible, based on wind direction, wind speed, and module inclination. We show that 30–45% increases in convection are possible through an array-flow informed approach to layout design, leading to a potential overall power increase of ~5% and decrease of solar panel degradation by +0.3%/year. The proposed method promises to augment performance without abandoning current PV panel designs, allowing for practical adoption into the existing industry. Previous models demonstrating the sensitivity to convection are validated through the wind tunnel results, and a new conceptual framework is provided that can lead to new means of solar PV array optimization.
Machine learning based identification of relevant parameters for functional voice disorders derived from endoscopic high-speed recordings
Authors: Schlegel Patrick , Kniesburges Stefan , Dürr Stephan , Schützenberger Anne , Döllinger Michael 
Published: June 2020

AbstractIn voice research and clinical assessment, many objective parameters are in use. However, there is no commonly used set of parameters that reflect certain voice disorders, such as functional dysphonia (FD); i.e. disorders with no visible anatomical changes. Hence, 358 high-speed videoendoscopy (HSV) recordings (159 normal females (NF), 101 FD females (FDF), 66 normal males (NM), 32 FD males (FDM)) were analyzed. We investigated 91 quantitative HSV parameters towards their significance. First, 25 highly correlated parameters were discarded. Second, further 54 parameters were discarded by using a LogitBoost decision stumps approach. This yielded a subset of 12 parameters sufficient to reflect functional dysphonia. These parameters separated groups NF vs. FDF and NM vs. FDM with fair accuracy of 0.745 or 0.768, respectively. Parameters solely computed from the changing glottal area waveform (1D-function called GAW) between the vocal folds were less important than parameters describing the oscillation characteristics along the vocal folds (2D-function called Phonovibrogram). Regularity of GAW phases and peak shape, harmonic structure and Phonovibrogram-based vocal fold open and closing angles were mainly important. This study showed the high degree of redundancy of HSV-voice-parameters but also affirms the need of multidimensional based assessment of clinical data.
Characteristics of autologous protein solution and leucocyte-poor platelet-rich plasma for the treatment of osteoarthritis of the knee
Authors: Wasai Shiho , Sato Masato , Maehara Miki , Toyoda Eriko , Uchiyama Ryoka , Takahashi Takumi , Okada Eri , Iwasaki Yoshiko , Suzuki Satoko , Watanabe Masahiko 
Published: June 2020

AbstractRecently, platelet-rich plasma (PRP) has received attention as a treatment for patients with osteoarthritis of the knee (OAK), a chronic degenerative disease, to bridge the gap between conservative and surgical treatments. Here, we investigated the differences in the humoral factors present in two types of PRP purified using the Autologous Protein Solution (APS) kit (group Z; leucocyte-rich PRP) or the Cellaid Serum Collection Set P type (group J; leucocyte-poor [LP]-PRP). Differences in humoral factors between healthy subjects (n = 10) and OAK patients (n = 12; group Z = 6, group J = 6), and the relationship between humoral factors and clinical outcome scores were investigated. Both anti-inflammatory and inflammatory cytokines were highly enriched in APS. The concentrations of tumour necrosis factor (TNF)-α, platelet-derived growth factor, fibroblast growth factor, soluble TNF-receptor 2, soluble Fas and transforming growth factor-β1 were higher in group Z, while the total amounts were higher in group J. The concentration of interleukin-1 receptor antagonist was positively correlated with the magnitude of change in the clinical outcome score and may contribute to improving knee-joint function. This is the first description of the humoral factors in APS and LP-PRP prepared from healthy subjects or OAK patients of Asian descent.
Extracellular glucose is crucially involved in the fate decision of LPS-stimulated RAW264.7 murine macrophage cells
Authors: Aki Toshihiko , Funakoshi Takeshi , Noritake Kanako , Unuma Kana , Uemura Koichi 
Published: June 2020

AbstractPyroptosis, a type of inflammatory cell death, is dependent on the inflammatory caspase-mediated cleavage of gasdermin D (GSDMD), and the subsequent pore formation on plasma membranes through which interleukin (IL)-1β and IL-18 are released from cells. During proinflammatory activation, macrophages shift their metabolism from aerobic oxidative phosphorylation to anaerobic glycolysis. Hypoxia-inducible factor (HIF)1α is involved in the induction of IL-1β gene expression as well as the metabolic shift towards glycolysis. However, the relationships between pyroptosis and glycolysis, as well as between pyroptosis and HIF1α are poorly investigated. Here we show that lipopolysaccharide (LPS) stimulation of RAW264.7 murine macrophage cells results in pyroptosis when cells are cultured in high glucose medium. During pyroptosis, HIF1α activation occurs transiently followed by downregulation to sub-basal levels. HIF1α downregulation and pyroptosis are observed when cells are stimulated with LPS under high glucose conditions. We also found that intracellular levels of methylglyoxal (MGO), a side product of glycolysis, increase when cells are stimulated with LPS under high glucose conditions. The addition of glycolysis inhibitor and rapamycin suppresses HIF1α downregulation and pyroptosis. These results show that glycolysis plays a crucial role not only in pro-inflammatory activation, but also in pyroptosis in LPS-stimulated RAW264.7 macrophages.
Doublecortin-like kinase 1 promotes hepatocyte clonogenicity and oncogenic programming via non-canonical β-catenin-dependent mechanism
Authors: Ali Naushad , Nguyen Charles B. , Chandrakesan Parthasarathy , Wolf Roman F. , Qu Dongfeng , May Randal , Goretsky Tatiana , Fazili Javid , Barrett Terrence A. , Li Min , Huycke Mark M. , Bronze Michael S. , Houchen Courtney W. 
Published: June 2020

AbstractChronic liver injury is a risk factor for cirrhosis and hepatocellular carcinoma (HCC). The molecular mechanisms that regulate the decision between normal injury repair and neoplastic initiation are unclear. Doublecortin-like kinase 1 (DCLK1), a tumor stem cell marker, is induced during cirrhosis and HCC. Here, we demonstrate that DCLK1-overexpressing primary human hepatocytes formed spheroids in suspension cultures. Spheroids derived from DCLK1-overexpressing hepatoma cells showed high level expression of active β-catenin, α-fetoprotein, and SOX9, suggesting that DCLK1 overexpression induces clonogenicity and dedifferentiated phenotypes in hepatoma cells. DCLK1 overexpression in hepatoma cells also increased phosphorylation of GSK-3β at Ser9. This was associated with an induction of a 48-kDa active β-catenin with a preserved hypophosphorylated N-terminus that interacted with nuclear TCF-4 resulting in luciferase reporter activity and cyclin D1 expression. DCLK1 downregulation inhibited 48-kDa β-catenin expression. The proteasome inhibitor bortezomib did not block the 48-kDa β-catenin, instead, caused a threefold accumulation, suggesting a proteasome-independent mechanism. Liver tissues from patients with cirrhosis and HCC revealed epithelial co-staining of DCLK1 and active β-catenin, and cleaved E-cadherin. Repopulated DCLK1-overexpressing primary human hepatocytes in humanized FRG mouse livers demonstrated active β-catenin. In conclusion, DCLK1 regulates oncogenic signaling and clonogenicity of hepatocytes by a novel non-canonical/atypical β-catenin-dependent mechanism.
Analyzing microglial-associated Aβ in Alzheimer’s disease transgenic mice with a novel mid-domain Aβ-antibody
Authors: Henjum Kristi , Årskog Vibeke , Jendresen Charlotte B. , Fladby Tormod , Torp Reidun , Nilsson Lars N. G. 
Published: June 2020

AbstractThe mechanisms of amyloid-β (Aβ)-degradation and clearance in Alzheimer’s disease (AD) pathogenesis have been relatively little studied. Short Aβ-fragments form by enzymatic cleavage and alternate amyloid-beta precursor protein (APP)-processing. Here we characterized a novel polyclonal Aβ-antibody raised against an Aβ mid-domain and used it to investigate microglial Aβ-uptake in situ by microscopy at the light- and ultrastructural levels. The rabbit Aβ-mid-domain antibody (ab338), raised against the mid-domain amino acids 21–34 (Aβ21–34), was characterized with biochemical and histological techniques. To identify the epitope in Aβ recognized by ab338, solid phase and solution binding data were compared with peptide folding scores as calculated with the Tango software. The ab338 antibody displayed high average affinity (KD: 6.2 × 10−10 M) and showed preference for C-terminal truncated Aβ-peptides ending at amino acid 34 and Aβ-mid domain peptides with high scores of β-turn structure. In transgenic APP-mouse brain, ab338 labelled amyloid plaques and detected Aβ-fragments in microglia at the ultra- and light microscopic levels. This reinforces a role of microglia/macrophages in Aβ-clearance in vivo. The ab338 antibody might be a valuable tool to study Aβ-clearance by microglial uptake and Aβ-mid-domain peptides generated by enzymatic degradation and alternate production.