bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic characterization of culture-associated changes in murine and human precision-cut tissue slices
Authors: Bigaeva Emilia , Gore Emilia , Simon Eric , Zwick Matthias , Oldenburger Anouk , de Jong Koert P. , Hofker Hendrik S. , Schlepütz Marco , Nicklin Paul , Boersema Miriam , Rippmann Jörg F. , Olinga Peter 
Published: November 2019

AbstractOur knowledge of complex pathological mechanisms underlying organ fibrosis is predominantly derived from animal studies. However, relevance of animal models for human disease is limited; therefore, an ex vivo model of human precision-cut tissue slices (PCTS) might become an indispensable tool in fibrosis research and drug development by bridging the animal–human translational gap. This study, presented as two parts, provides comprehensive characterization of the dynamic transcriptional changes in PCTS during culture by RNA sequencing. Part I investigates the differences in culture-induced responses in murine and human PCTS derived from healthy liver, kidney and gut. Part II delineates the molecular processes in cultured human PCTS generated from diseased liver, kidney and ileum. We demonstrated that culture was associated with extensive transcriptional changes and impacted PCTS in a universal way across the organs and two species by triggering an inflammatory response and fibrosis-related extracellular matrix (ECM) remodelling. All PCTS shared mRNA upregulation of IL-11 and ECM-degrading enzymes MMP3 and MMP10. Slice preparation and culturing activated numerous pathways across all PCTS, especially those involved in inflammation (IL-6, IL-8 and HMGB1 signalling) and tissue remodelling (osteoarthritis pathway and integrin signalling). Despite the converging effects of culture, PCTS display species-, organ- and pathology-specific differences in the regulation of genes and canonical pathways. The underlying pathology in human diseased PCTS endures and influences biological processes like cytokine release. Our study reinforces the use of PCTS as an ex vivo fibrosis model and supports future studies towards its validation as a preclinical tool for drug development.
Multiple Solutions to a Nonlinear Curl–Curl Problem in $${\mathbb {R}}^3$$
Authors: Mederski Jarosław , Schino Jacopo , Szulkin Andrzej 
Published: November 2019

AbstractWe look for ground states and bound states $$E:{\mathbb {R}}^3\rightarrow {\mathbb {R}}^3$$E:R3→R3 to the curl–curl problem $$\begin{aligned} \nabla \times (\nabla \times E)= f(x,E) \qquad \text { in } {\mathbb {R}}^3, \end{aligned}$$∇×(∇×E)=f(x,E)inR3,which originates from nonlinear Maxwell equations. The energy functional associated with this problem is strongly indefinite due to the infinite dimensional kernel of $$\nabla \times (\nabla \times \cdot )$$∇×(∇×·). The growth of the nonlinearity f is controlled by an N-function $$\Phi :{\mathbb {R}}\rightarrow [0,\infty )$$Φ:R→[0,∞) such that $$\displaystyle \lim _{s\rightarrow 0}\Phi (s)/s^6=\lim _{s\rightarrow +\infty }\Phi (s)/s^6=0$$lims→0Φ(s)/s6=lims→+∞Φ(s)/s6=0. We prove the existence of a ground state, that is, a least energy nontrivial solution, and the existence of infinitely many geometrically distinct bound states. We improve previous results concerning ground states of curl–curl problems. Multiplicity results for our problem have not been studied so far in $${\mathbb {R}}^3$$R3 and in order to do this we construct a suitable critical point theory; it is applicable to a wide class of strongly indefinite problems, including this one and Schrödinger equations.
Visualizing large-scale flow using synthetic aperture PIV
Authors: van Houwelingen Josje , Holten Ad P. C. , Clercx Herman J. H. , Kunnen Rudie P. J. , Molenaar Jaap , van de Water Willem 
Published: November 2019

Abstract
We discuss the application of synthetic aperture particle image velocimetry for measuring the flow around human swimmers using small bubbles as tracer. We quantify the two-dimensional projection of the velocity field in planes perpendicular to the viewing direction of an array of six cameras. With help of simulations, modelled after the experiment, we address questions about depth selectivity and occlusion in dense bubble fields. Using vortex rings in the swimming pool, we provide a proof of principle of the method. It is further illustrated by the vorticity field produced by a human swimmer.

Graphic abstract
Using personalized medicine in gliomas: a genomic approach to diagnosis and overcoming treatment resistance in a case with pleomorphic xanthoastrocytoma
Authors: Piña Yolanda , Fusco Michael J. , Macaulay Robert J. , Walko Christine M. , Peguero Edwin , Evernden Brittany R. , Smalley Keiran S. , Forsyth Peter 
Published: November 2019

Abstract
Introduction
A patient who was initially considered to have a glioblastoma (GBM) had molecular analysis, showing that it was a pleomorphic xanthoastrocytoma (PXA). Up to 78% of PXA tumors have BRAF V600E mutations. Primary brain tumors with BRAF mutations can have a good response to BRAF MEK inhibitors (BRAF MEKi), and there may be a synergistic response when combined with autophagy inhibitors.

Presentation of the case
A 20-year-old man found to have a large brain mass with midline shift underwent resection. He was diagnosed with “GBM” and treated with radiation and temozolomide with subsequent disease recurrence. Review of histology showed malignant PXA with BRAF V600E mutation. Treatment with Dabrafenib and Trametinib was started, and tumor size increased in size after 14 months of treatment. Given studies showing that resistance to BRAF inhibition can be overcome by autophagy inhibition, chloroquine was added. Patient has been on “triple” therapy for 15 months and has radiographically Stable Disease. At MCC, 3% of patients with gliomas have BRAF mutations who could potentially benefit from this combination therapy.

Conclusion
This is the first report of a PXA patient receiving therapy with BRAF MEKi and an autophagy inhibitor with prolonged stable disease. This patient highlights the importance of a molecular interrogation in gliomas to provide an integrated diagnosis and effective treatment. This may be useful in up to 3% of glioma patients with BRAF mutations. Molecular testing in neuro-oncology is providing new avenues of diagnosis and treatment, and detailed molecular interrogation should be considered routine.
Economic evaluation of meningococcal vaccines: considerations for the future
Authors: Christensen Hannah , Al-Janabi Hareth , Levy Pierre , Postma Maarten J. , Bloom David E. , Landa Paolo , Damm Oliver , Salisbury David M. , Diez-Domingo Javier , Towse Adrian K. , Lorgelly Paula K. , Shah Koonal K. , Hernandez-Villafuerte Karla , Smith Vinny , Glennie Linda , Wright Claire , York Laura , Farkouh Raymond 
Published: November 2019

AbstractIn 2018, a panel of health economics and meningococcal disease experts convened to review methodologies, frameworks, and decision-making processes for economic evaluations of vaccines, with a focus on evaluation of vaccines targeting invasive meningococcal disease (IMD). The panel discussed vaccine evaluation methods across countries; IMD prevention benefits that are well quantified using current methods, not well quantified, or missing in current cost-effectiveness methodologies; and development of recommendations for future evaluation methods. Consensus was reached on a number of points and further consideration was deemed necessary for some topics. Experts agreed that the unpredictability of IMD complicates an accurate evaluation of meningococcal vaccine benefits and that vaccine cost-effectiveness evaluations should encompass indirect benefits, both for meningococcal vaccines and vaccines in general. In addition, the panel agreed that transparency in the vaccine decision-making process is beneficial and should be implemented when possible. Further discussion is required to ascertain: how enhancing consistency of frameworks for evaluating outcomes of vaccine introduction can be improved; reviews of existing tools used to capture quality of life; how indirect costs are considered within models; and whether and how the weighting of quality-adjusted life-years (QALY), application of QALY adjustment factors, or use of altered cost-effectiveness thresholds should be used in the economic evaluation of vaccines.
A novel method based on nonparametric regression with a Gaussian kernel algorithm identifies the critical components in CHO media and feed optimization
Authors: Zou Mao , Zhou Zi-Wei , Fan Li , Zhang Wei-Jian , Zhao Liang , Liu Xu-Ping , Wang Hai-Bin , Tan Wen-Song 
Published: November 2019

Abstract
As the composition of animal cell culture medium becomes more complex, the identification of key variables is important for simplifying and guiding the subsequent medium optimization. However, the traditional experimental design methods are impractical and limited in their ability to explore such large feature spaces. Therefore, in this work, we developed a NRGK (nonparametric regression with Gaussian kernel) method, which aimed to identify the critical components that affect product titres during the development of cell culture media. With this nonparametric model, we successfully identified the important components that were neglected by the conventional PLS (partial least squares regression) method. The superiority of the NRGK method was further verified by ANOVA (analysis of variance). Additionally, it was proven that the selection accuracy was increased with the NRGK method because of its ability to model both the nonlinear and linear relationships between the medium components and titres. The application of this NRGK method provides new perspectives for the more precise identification of the critical components that further enable the optimization of media in a shorter timeframe.
EndOxy: Dynamic Long-Term Evaluation of Endothelialized Gas Exchange Membranes for a Biohybrid Lung
Authors: Klein Sarah , Hesselmann Felix , Djeljadini Suzana , Berger Tanja , Thiebes Anja Lena , Schmitz-Rode Thomas , Jockenhoevel Stefan , Cornelissen Christian G 
Published: November 2019

AbstractIn the concept of a biohybrid lung, endothelial cells seeded on gas exchange membranes form a non-thrombogenic an anti-inflammatory surface to overcome the lacking hemocompatibility of today’s oxygenators during extracorporeal membrane oxygenation. To evaluate this concept, the long-term stability and gas exchange performance of endothelialized RGD-conjugated polydimethylsiloxane (RGD-PDMS) membranes was evaluated. Human umbilical vein endothelial cells (ECs) were cultured on RGD-PDMS in a model system under physiological wall shear stress (WSS) of 0.5 Pa for up to 33 days. Gas exchange performance was tested with three biological replicates under elevated WSS of 2.5 Pa using porcine blood adjusted to venous values following ISO 7199 and blood gas analysis. EC morphology was assessed by immunocytochemistry (n= 3). RGD-PDMS promoted endothelialization and stability of endothelialized membranes was shown for at least 33 days and for a maximal WSS of 2.5 Pa. Short-term exposure to porcine blood did not affect EC integrity. The gas transfer tests provided evidence for the oxygenation and decarboxylation of the blood across endothelialized membranes with a decrease of transfer rates over time that needs to be addressed in further studies with larger sample sizes. Our results demonstrate the general suitability of RGD-PDMS for biohybrid lung applications, which might enable long-term support of patients with chronic lung failure in the future.
A note on the Gao et al. (2019) uniform mixture model in the case of regression
Authors: Tsionas Mike G. , Andrikopoulos Athanasios 
Published: November 2019

AbstractWe extend the uniform mixture model of Gao et al. (Ann Oper Res, 2019. 10.1007/s10479-019-03236-9) to the case of linear regression. Gao et al. (Ann Oper Res, 2019. 10.1007/s10479-019-03236-9) proposed that to characterize the probability distributions of multimodal and irregular data observed in engineering, a uniform mixture model can be used. This model is a weighted combination of multiple uniform distribution components. This case is of empirical interest since, in many instances, the distribution of the error term in a linear regression model cannot be assumed unimodal. Bayesian methods of inference organized around Markov chain Monte Carlo are proposed. In a Monte Carlo experiment, significant efficiency gains are found in comparison to least squares justifying the use of the uniform mixture model.
Hybrid master equation for jump-diffusion approximation of biomolecular reaction networks
Authors: Altıntan Derya , Koeppl Heinz 
Published: November 2019

AbstractCellular reactions have a multi-scale nature in the sense that the abundance of molecular species and the magnitude of reaction rates can vary across orders of magnitude. This diversity naturally leads to hybrid models that combine continuous and discrete modeling regimes. In order to capture this multi-scale nature, we proposed jump-diffusion approximations in a previous study. The key idea was to partition reactions into fast and slow groups, and then to combine a Markov jump updating scheme for the slow group with a diffusion (Langevin) updating scheme for the fast group. In this study we show that the joint probability density function of the jump-diffusion approximation over the reaction counting process satisfies a hybrid master equation that combines terms from the chemical master equation and from the Fokker–Planck equation. Inspired by the method of conditional moments, we propose a efficient method to solve this master equation using the moments of reaction counters of the fast reactions given the reaction counters of the slow reactions. For each time point of interest, we then solve a set of maximum entropy problems in order to recover the conditional probability density from its moments. This finally allows us to reconstruct the complete joint probability density over all reaction counters and hence obtain an approximate solution of the hybrid master equation. Finally, we show the accuracy of the method applied to a simple multi-scale conversion process.
Unpacking Transient Event Dynamics in Electrophysiological Power Spectra
Authors: Quinn Andrew J. , van Ede Freek , Brookes Matthew J. , Heideman Simone G. , Nowak Magdalena , Seedat Zelekha A. , Vidaurre Diego , Zich Catharina , Nobre Anna C. , Woolrich Mark W. 
Published: November 2019

AbstractElectrophysiological recordings of neuronal activity show spontaneous and task-dependent changes in their frequency-domain power spectra. These changes are conventionally interpreted as modulations in the amplitude of underlying oscillations. However, this overlooks the possibility of underlying transient spectral ‘bursts’ or events whose dynamics can map to changes in trial-average spectral power in numerous ways. Under this emerging perspective, a key challenge is to perform burst detection, i.e. to characterise single-trial transient spectral events, in a principled manner. Here, we describe how transient spectral events can be operationalised and estimated using Hidden Markov Models (HMMs). The HMM overcomes a number of the limitations of the standard amplitude-thresholding approach to burst detection; in that it is able to concurrently detect different types of bursts, each with distinct spectral content, without the need to predefine frequency bands of interest, and does so with less dependence on a priori threshold specification. We describe how the HMM can be used for burst detection and illustrate its benefits on simulated data. Finally, we apply this method to empirical data to detect multiple burst types in a task-MEG dataset, and illustrate how we can compute burst metrics, such as the task-evoked timecourse of burst duration.
Preconditions for bioenergy with carbon capture and storage (BECCS) in sub-Saharan Africa: the case of Tanzania
Authors: Hansson Anders , Fridahl Mathias , Haikola Simon , Yanda Pius , Pauline Noah , Mabhuye Edmund 
Published: November 2019

AbstractMost mitigation scenarios compatible with a likely change of holding global warming well below 2 °C rely on negative emissions technologies (NETs). According to the integrated assessment models (IAMs) used to produce mitigation scenarios for the IPCC reports, the NET with the greatest potential to achieve negative emissions is bioenergy with carbon capture and storage (BECCS). Crucial questions arise about where the enormous quantities of biomass needed according to the IAM scenarios could feasibly be produced in a sustainable manner. Africa is attractive in the context of BECCS because of large areas that could contribute biomass energy and indications of substantial underground CO2 storage capacities. However, estimates of large biomass availability in Africa are usually based on highly aggregated datasets, and only a few studies explore future challenges or barriers for BECCS in any detail. Based on previous research and literature, this paper analyses the pre-conditions for BECCS in Tanzania by studying what we argue are the applications of BECCS, or the components of the BECCS chain, that are most feasible in the country, namely (1) as applied to domestic sugarcane-based energy production (bioethanol), and (2) with Tanzania in a producer and re-growth role in an international BECCS chain, supplying biomass or biofuels for export to developed countries. The review reveals that a prerequisite for both options is either the existence of a functional market for emissions trading and selling, making negative emissions a viable commercial investment, or sustained investment through aid programmes. Also, historically, an important barrier to the development of production capacity of liquid biofuels for export purposes has been given by ethical dilemmas following in the wake of demand for land to facilitate production of biomass, such as sugarcane and jatropha. In these cases, conflicts over access to land and mismanagement have been more of a rule than an exception. Increased production volumes of solid biomass for export to operations that demand bioenergy, be it with or without a CCS component, is likely to give rise to similar conflicts. While BECCS may well play an important role in reducing emissions in countries with high capacity to act combined with existing large point sources of biogenic CO2 emissions, it seems prudent to proceed with utmost caution when implicating BECCS deployment in least developed countries, like Tanzania.The paper argues that negative BECCS-related emissions from Tanzania should not be assumed in global climate mitigation scenarios.
Human health in systemic adaptation to climate change: insights from flood risk management in a river basin
Authors: Assmuth Timo , Dubrovin Tanja , Lyytimäki Jari 
Published: November 2019

AbstractHuman health risks in dealing with floods in a river basin in South-Western Finland are analysed as an example of scientific and practical challenges in systemic adaptation to climate change and in integrated governance of water resources. The analysis is based on case reports and plans, on literature studies and on conceptual models of risks and risk management. Flood risks in the Northern European study area are aggravated by melt- and storm-water runoff, ice jams and coastal flooding. Flood risk assessment is linked with management plans based on EU directives as applied in the case area. National risk management policies and procedures of increasing scope and depth have been devised for climate change, water resources and overall safety, but an integrated approach to health risks is still largely missing. The same is true of surveys of perceived flood risks, and participatory deliberation and collaborative planning procedures for flood risk management in the case area, specifically for adaptive lake regulation. Health impacts, risks and benefits, socio-economic and systemic risks, and over-arching prevention, adaptation and compensation measures are not fully included. We propose a systematic framework for these extensions. Particular attention needs to be given to health risks due to flooding, e.g. from water contamination, moist buildings, mental stress and infrastructure damage and also from management actions. Uncertainties and ambiguities about risks present continuing challenges. It is concluded that health aspects of flooding are complex and need to be better included in assessment and control, to develop more integrated and adaptive systemic risk governance.
Critical Factors Determining the Onset of Backdraft Using Solid Fuels
Authors: Wu Chia Lung , Santamaria Simón , Carvel Ricky 
Published: November 2019

AbstractBackdraft is an explosive fire phenomenon which typically occurs during fire-fighting activities, occasionally leading to fire-fighter fatalities. Real backdraft incidents involve complex fuel gas mixtures consisting of the products of underventilated burning and pyrolysis following burnout. However, most experimental research into backdraft has used methane gas or flammable liquids as fuel. Some aspects of real backdraft behavior may have been overlooked as a consequence of this simplicity. A reduced scale series of compartment fire tests have been carried out to investigate the critical factors governing the onset of backdraft, using polypropylene and high density polyethylene samples as fuel. It is established that there are critical temperatures for auto-ignition of the pyrolysis gases leading to backdraft which vary with fuel properties. For polypropylene the highest temperature in the compartment must be above 350°C for auto-ignition of the fuel gases, while mixtures in the presence of a pilot source can be ignited down to about 320°C. Backdraft cannot occur when the compartment temperature is below 320°C. For polyethylene, the corresponding temperature for auto-ignition is 320°C. In parallel with these tests, a series of pyrolysis investigations have been carried out using the fire propagation apparatus, with FTIR gas analysis. The observed critical temperatures for backdraft correlate well with the evolved pyrolysis gases. Analysis shows that higher temperatures are required for backdraft when the CO/CO2 ratio is small, and that below the auto-ignition temperature, backdraft can only occur above a CO/CO2 ratio of about 35%. It is concluded that the crucial factors determining whether backdraft occurs or not are the maximum temperature and the CO/CO2 ratio in the compartment, prior to opening the door.
Application of the Langmuir Technique to Study the Response of C-dec-9-en-1-ylcalix[4]resorcinarene and C-undecylcalix[4]resorcinarene Ultra-thin Films' Interactions with Cd2+, Hg2+, Pb2+, and Cu2+ Cations Present in the Subphase
Authors: Eddaif Larbi , Shaban Abdul , Telegdi Judit 
Published: November 2019

AbstractThe calix[4]resorcinarene macrocycles are excellent oligomers for the design of amphiphilic derivatives; they can form self-assemblies and stable sensing networks. Owing to their favorable properties, they are the focus of many exploitations and studies ranging from biological controls to heavy metal ion sensing. In this perspective, two calix[4]resorcinarene derivatives, namely: C-dec-9-en-1-ylcalix[4]resorcinarene (ionophore I) and C-undecylcalix[4]resorcinarene (ionophore II) were used to form stable ultra-thin Langmuir monolayer films at the air/water interface; their interactions with different harmful metal cations (Cd2+, Pb2+, Hg2+, and Cu2+) were studied and highlighted via the pressure-area (Π-A) isotherms. The obtained results in the current investigation showed a dependence of both macrocycle interactions on the metal cation concentration in the subphase, confirming their complexation. In addition, the ionophore (I) exhibited high selectivity towards Pb2+ and Cu2+ cations, whereas the ionophore (II) showed tendency to bind with Cu2+ cations over others, approving the potential applicability of these macrocycles as ion selective chemical sensors.