bluuebunny/crossref_metadata_2025_split huggingface dataset:
Introducing an Optimization- and explicit Runge-Kutta- based Approach to Perform Dynamic Flux Balance Analysis
Authors: Schroeder Wheaton L. , Saha Rajib 
Published: June 2020

AbstractIn this work we introduce the generalizedOptimization- and explicitRunge-Kutta-basedApproach (ORKA) to performdynamicFluxBalanceAnalysis (dFBA), which is numerically more accurate and computationally tractable than existing approaches. ORKA is applied to a four-tissue (leaf, root, seed, and stem) model ofArabidopsis thaliana, p-ath773, uniquely capturing the core-metabolism of several stages of growth from seedling to senescence at hourly intervals. Model p-ath773 has been designed to show broad agreement with published plant-scale properties such as mass, maintenance, and senescence, yet leaving reaction-level behavior unconstrainted. Hence, it serves as a framework to study the reaction-level behavior necessary for observed plant-scale behavior. Two such case studies of reaction-level behavior include the lifecycle progression of sulfur metabolism and the diurnal flow of water throughout the plant. Specifically, p-ath773 shows how transpiration drives water flow through the plant and how water produced by leaf tissue metabolism may contribute significantly to transpired water. Investigation of sulfur metabolism elucidates frequent cross-compartment exchange of a standing pool of amino acids which is used to regulate the proton flow. Overall, p-ath773 and ORKA serve as scaffolds for dFBA-based lifecycle modeling of plants and other systems to further broaden the scope ofin silicometabolic investigation.
Vestibular stimulation by 2G hypergravity modifies resynchronization in temperature rhythm in rats
Authors: Martin Tristan , Bonargent Tristan , Besnard Stéphane , Quarck Gaëlle , Mauvieux Benoit , Pigeon Eric , Denise Pierre , Davenne Damien 
Published: June 2020

AbstractInput from the light/dark (LD) cycle constitutes the primary synchronizing stimulus for the suprachiasmatic nucleus (SCN) circadian clock. However, the SCN can also be synchronized by non-photic inputs. Here, we hypothesized that the vestibular system, which detects head motion and orientation relative to gravity, may provide sensory inputs to synchronize circadian rhythmicity. We investigated the resynchronization of core temperature (Tc) circadian rhythm to a six-hour phase advance of the LD cycle (LD + 6) using hypergravity (2 G) as a vestibular stimulation in control and bilateral vestibular loss (BVL) rats. Three conditions were tested: an LD + 6 exposure alone, a series of seven 2 G pulses without LD + 6, and a series of seven one-hour 2 G pulses (once a day) following LD + 6. First, following LD + 6, sham rats exposed to 2 G pulses resynchronized earlier than BVL rats (p = 0.01), and earlier than sham rats exposed to LD + 6 alone (p = 0.002). Each 2 G pulse caused an acute drop of Tc in sham rats (−2.8 ± 0.3 °C; p < 0.001), while BVL rats remained unaffected. This confirms that the vestibular system influences chronobiological regulation and supports the hypothesis that vestibular input, like physical activity, should be considered as a potent time cue for biological rhythm synchronization, acting in synergy with the visual system.
Potential Utilisation of Dark-Fermented Palm Oil Mill Effluent in Continuous Production of Biomethane by Self-Granulated Mixed Culture
Authors: Mahmod Safa Senan , Azahar Azratul Madihah , Luthfi Abdullah Amru Indera , Abdul Peer Mohamed , Mastar Mohd Shahbudin , Anuar Nurina , Takriff Mohd Sobri , Jahim Jamaliah M. D. 
Published: June 2020

AbstractTwo-stage anaerobic digestion of palm oil mill effluent (POME) is a promising method for converting the waste from the largest agricultural industry in Southeast Asia into a clean and sustainable energy. This study investigates the degradation of acid-rich effluent from the dark fermentation stage for the production of biomethane (BioCH4) in a 30-L continuous stirred-tank reactor (CSTR). The continuous methanogenic process was operated with varied HRTs (10 - 1 day) and OLRs (4.6–40.6 gCOD/L.d−1) under thermophilic conditions. Methanothermobacter sp. was the dominant thermophilic archaea that was responsible for the production rate of 4.3 LCH4/LPOME.d−1 and methane yield of 256.77 LCH4kgCOD at HRT of 2 d, which is the lowest HRT reported in the literature. The process was able to digest 85% and 64% of the initial POME’s COD and TSS, respectively. The formation of methane producing granules (MPG) played a pivotal role in sustaining the efficient and productive anaerobic system. We report herein that the anaerobic digestion was not only beneficial in reducing the contaminants in the liquid effluent, but generating BioCH4 gas with a positive net energy gain of 7.6 kJ/gCOD.
Flexible endoscopic micro-optical coherence tomography for three-dimensional imaging of the arterial microstructure
Authors: Kim Junyoung , Kim Sunwon , Song Joon Woo , Kim Hyun Jung , Lee Min Woo , Han Jeongmoo , Kim Jin Won , Yoo Hongki 
Published: June 2020

AbstractMicro-optical coherence tomography (µOCT) is a novel imaging approach enabling visualization of the microstructures of biological tissues at a cellular or sub-cellular level. However, it has been challenging to develop a miniaturized flexible endoscopic µOCT probe allowing helical luminal scanning. In this study, we built a flexible endoscopic µOCT probe with an outer diameter of 1.2 mm, which acquires three-dimensional images of the arterial microstructures via helical scanning with an axial and lateral resolutions of 1.83 µm and 3.38 µm in air, respectively. Furthermore, the depth of focus of the µOCT imaging probe was extended two-fold using a binary phase spatial filter. We demonstrated that the present endoscopic µOCT could image cellular level features of a rabbit artery with high-risk atheroma and a bioresorbable scaffold-implanted swine coronary artery. This highly-translatable endoscopic µOCT will be a useful tool for investigating coronary artery disease and stent biology.
Cellular absorption of small molecules: free energy landscapes of melatonin binding at phospholipid membranes
Authors: Lu Huixia , Marti Jordi 
Published: June 2020

AbstractFree energy calculations are essential to unveil mechanisms at the atomic scale such as binding of small solutes and their translocation across cell membranes, eventually producing cellular absorption. Melatonin regulates biological rhythms and is directly related to carcinogenesis and neurodegenerative disorders. Free energy landscapes obtained from well-tempered metadynamics simulations precisely describe the characteristics of melatonin binding to specific sites in the membrane and reveal the role of cholesterol in free energy barrier crossing. A specific molecular torsional angle and the distance between melatonin and the center of the membrane along the normal to the membrane Z-axis have been considered as suitable reaction coordinates. Free energy barriers between two particular orientations of the molecular structure (folded and extended) have been found to be of about 18 kJ/mol for z-distances of about 1–2 nm. The ability of cholesterol to expel melatonin out of the internal regions of the membrane towards the interface and the external solvent is explained from a free energy perspective. The calculations reported here offer detailed free energy landscapes of melatonin embedded in model cell membranes and reveal microscopic information on its transition between free energy minima, including the location of relevant transition states, and provide clues on the role of cholesterol in the cellular absorption of small molecules.
Enhanced tenacity of mycobacterial aerosols from necrotic neutrophils
Authors: Pfrommer E. , Dreier C. , Gabriel G. , Dallenga T. , Reimer R. , Schepanski K. , Scherließ R. , Schaible U. E. , Gutsmann T. 
Published: June 2020

AbstractThe tuberculosis agent Mycobacterium tuberculosis is primarily transmitted through air, but little is known about the tenacity of mycobacterium-containing aerosols derived from either suspensions or infected neutrophils. Analysis of mycobacterial aerosol particles generated from bacterial suspensions revealed an average aerodynamic diameter and mass density that may allow distant airborne transmission. The volume and mass of mycobacterial aerosol particles increased with elevated relative humidity. To more closely mimic aerosol formation that occurs in active TB patients, aerosols from mycobacterium-infected neutrophils were analysed. Mycobacterium-infected intact neutrophils showed a smaller particle size distribution and lower viability than free mycobacteria. In contrast, mycobacterium-infected necrotic neutrophils, predominant in M. tuberculosis infection, revealed particle sizes and viability rates similar to those found for free mycobacteria, but in addition, larger aggregates of viable mycobacteria were observed. Therefore, mycobacteria are shielded from environmental stresses in multibacillary aggregates generated from necrotic neutrophils, which allows improved tenacity but emphasizes short distance transmission between close contacts.
A heritable profile of six miRNAs in autistic patients and mouse models
Authors: Ozkul Yusuf , Taheri Serpil , Bayram Kezban Korkmaz , Sener Elif Funda , Mehmetbeyoglu Ecmel , Öztop Didem Behice , Aybuga Fatma , Tufan Esra , Bayram Arslan , Dolu Nazan , Zararsiz Gokmen , Kianmehr Leila , Beyaz Feyzullah , Doganyigit Züleyha , Cuzin François , Rassoulzadegan Minoo 
Published: June 2020

AbstractAutism spectrum disorder (ASD) is a group of developmental pathologies that impair social communication and cause repetitive behaviors. The suggested roles of noncoding RNAs in pathology led us to perform a comparative analysis of the microRNAs expressed in the serum of human ASD patients. The analysis of a cohort of 45 children with ASD revealed that six microRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) were expressed at low to very low levels compared to those in healthy controls. A similar but less pronounced decrease was registered in the clinically unaffected parents of the sick children and in their siblings but never in any genetically unrelated control. Results consistent with these observations were obtained in the blood, hypothalamus and sperm of two of the established mouse models of ASD: valproic acid-treated animals and Cc2d1a+/− heterozygotes. In both instances, the same characteristic miRNA profile was evidenced in the affected individuals and inherited together with disease symptoms in the progeny of crosses with healthy animals. The consistent association of these genetic regulatory changes with the disease provides a starting point for evaluating the changes in the activity of the target genes and, thus, the underlying mechanism(s). From the applied societal and medical perspectives, once properly confirmed in large cohorts, these observations provide tools for the very early identification of affected children and progenitors.
Ensilicated tetanus antigen retains immunogenicity: in vivo study and time-resolved SAXS characterization
Authors: Doekhie A. , Dattani R. , Chen Y-C. , Yang Y. , Smith A. , Silve A. P. , Koumanov F. , Wells S. A. , Edler K. J. , Marchbank K. J. , Elsen J. M. H. van den , Sartbaeva A. 
Published: June 2020

AbstractOur recently developed ensilication approach can physically stabilize proteins in silica without use of a pre-formed particle matrix. Stabilisation is done by tailor fitting individual proteins with a silica coat using a modified sol-gel process. Biopharmaceuticals, e.g. liquid-formulated vaccines with adjuvants, frequently have poor thermal stability; heating and/or freezing impairs their potency. As a result, there is an increase in the prevalence of vaccine-preventable diseases in low-income countries even when there are means to combat them. One of the root causes lies in the problematic vaccine ‘cold chain’ distribution. We believe that ensilication can improve vaccine availability by enabling transportation without refrigeration. Here, we show that ensilication stabilizes tetanus toxin C fragment (TTCF), a component of the tetanus toxoid present in the diphtheria, tetanus and pertussis (DTP) vaccine. Experimentalin vivoimmunization data show that the ensilicated material can be stored, transported at ambient temperatures, and even heat-treated without compromising the immunogenic properties of TTCF. To further our understanding of the ensilication process and its protective effect on proteins, we have also studied the formation of TTCF-silica nanoparticles via time-resolved Small Angle X-ray Scattering (SAXS). Our results reveal ensilication to be a staged diffusion-limited cluster aggregation (DLCA) type reaction. An early stage (tens of seconds) in which individual proteins are coated with silica is followed by a subsequent stage (several minutes) in which the protein-containing silica nanoparticles aggregate into larger clusters. Our results suggest that we could utilize this technology for vaccines, therapeutics or other biopharmaceuticals that are not compatible with lyophilization.
The effect of phytoglobin overexpression on the plant proteome during nonhost response of barley (Hordeum vulgare) to wheat powdery mildew (Blumeria graminis f. sp. tritici)
Authors: Andrzejczak O. A. , Sørensen C. K. , Wang W.-Q. , Kovalchuk S. , Hagensen C. E. , Jensen O. N. , Carciofi M. , Hovmøller M. S. , Rogowska-Wrzesinska A. , Møller I. M. , Hebelstrup K. H. 
Published: June 2020

AbstractNonhost resistance, a resistance of plant species against all nonadapted pathogens, is considered the most durable and efficient immune system in plants. To increase our understanding of the response of barley plants to infection by powdery mildew, Blumeria graminis f. sp. tritici, we used quantitative proteomic analysis (LC-MS/MS). We compared the response of two genotypes of barley cultivar Golden Promise, wild type (WT) and plants with overexpression of phytoglobin (previously hemoglobin) class 1 (HO), which has previously been shown to significantly weaken nonhost resistance. A total of 8804 proteins were identified and quantified, out of which the abundance of 1044 proteins changed significantly in at least one of the four comparisons (‘i’ stands for ‘inoculated’)- HO/WT and HOi/WTi (giving genotype differences), and WTi/WT and HOi/HO (giving treatment differences). Among these differentially abundant proteins (DAP) were proteins related to structural organization, disease/defense, metabolism, transporters, signal transduction and protein synthesis. We demonstrate that quantitative changes in the proteome can explain physiological changes observed during the infection process such as progression of the mildew infection in HO plants that was correlated with changes in proteins taking part in papillae formation and preinvasion resistance. Overexpression of phytoglobins led to modification in signal transduction prominently by dramatically reducing the number of kinases induced, but also in the turnover of other signaling molecules such as phytohormones, polyamines and Ca2+. Thus, quantitative proteomics broaden our understanding of the role NO and phytoglobins play in barley during nonhost resistance against powdery mildew.
G-computation, propensity score-based methods, and targeted maximum likelihood estimator for causal inference with different covariates sets: a comparative simulation study
Authors: Chatton Arthur , Le Borgne Florent , Leyrat Clémence , Gillaizeau Florence , Rousseau Chloé , Barbin Laetitia , Laplaud David , Léger Maxime , Giraudeau Bruno , Foucher Yohann 
Published: June 2020

AbstractControlling for confounding bias is crucial in causal inference. Distinct methods are currently employed to mitigate the effects of confounding bias. Each requires the introduction of a set of covariates, which remains difficult to choose, especially regarding the different methods. We conduct a simulation study to compare the relative performance results obtained by using four different sets of covariates (those causing the outcome, those causing the treatment allocation, those causing both the outcome and the treatment allocation, and all the covariates) and four methods: g-computation, inverse probability of treatment weighting, full matching and targeted maximum likelihood estimator. Our simulations are in the context of a binary treatment, a binary outcome and baseline confounders. The simulations suggest that considering all the covariates causing the outcome led to the lowest bias and variance, particularly for g-computation. The consideration of all the covariates did not decrease the bias but significantly reduced the power. We apply these methods to two real-world examples that have clinical relevance, thereby illustrating the real-world importance of using these methods. We propose an R package RISCA to encourage the use of g-computation in causal inference.
Establishment of a guided, in vivo, multi-channel, abdominal, tissue imaging approach
Authors: Bahlmann Julia , Madrahimov Nodir , Daniel Fiene , Theidel David , DeTemple Daphne E. , Buettner Manuela , Bleich André , Haverich Axel , Heisterkamp Alexander , Kalies Stefan 
Published: June 2020

AbstractNovel tools in humane animal research should benefit the animal as well as the experimentally obtained data. Imaging technologies have proven to be versatile and also in accordance with the demands of the 3 R principle. However, most imaging technologies are either limited by the target organs, number of repetitive imaging sessions, or the maximal resolution. We present a technique-, which enables multicolor abdominal imaging on a tissue level. It is based on a small imaging fiber endoscope, which is guided by a second commercial endoscope. The imaging fiber endoscope allows the distinction of four different fluorescence channels. It has a size of less than 1 mm and can approximately resolve single cells. The imaging fiber was successfully tested on cells in vitro, excised organ tissue, and in mice in vivo. Combined with neural networks for image restauration, high quality images from various abdominal organs of interest were realized. The second endoscope ensured a precise placement of the imaging fiber in vivo. Our approach of guided tissue imaging in vivo, combined with neuronal networks for image restauration, permits the acquisition of fluorescence-microscope like images with minimal invasive surgery in vivo. Therefore, it is possible to extend our approach to repetitive imaging sessions. The cost below 30 thousand euros allows an establishment of this approach in various scenarios.
Spin-splitting effects on the interband optical conductivity and activity of phosphorene
Authors: Phuong Le Thi Thu , Phong Tran C. , Yarmohammadi Mohsen 
Published: June 2020

AbstractBeing able to tune the anisotropic interband transitions in phosphorene at finite temperature offers an enormous amount of possibilities in finding new insights in the optoelectronic community. To contribute to this goal we propose a Zeeman spin-splitting field aiming at absorbing various frequencies of the incident light. Employing the tight-binding Hamiltonian to describe the carrier dynamics and the Kubo formalism to formulate the orientation-dependent interband optical conductivity (IOC) and optical activity of phosphorene we investigate the absorption and scattering mechanisms in phosphorene depending on the Zeeman field strength and optical energy parameters. The optical activity features are characterized by exploring the eccentricity and shift phase of reflected and transmitted electromagnetic waves of the incident light. Different electronic phases in the absence and presence of Zeeman field ultimate different types of interband transitions of which in all cases the IOC along the armchair direction is larger than the zigzag one. However, we observed an irregular (regular) process for IOC with the Zeeman field along the armchair (zigzag) direction, resulting in irregular (regular) absorption and scattering mechanisms. Additionally, a little to no effects for temperature-dependent IOC are provided with the Zeeman field in undoped phosphorene. Further, almost linearly and elliptically polarizations are reported for the transmitted and reflected waves, respectively, indicating that the phosphorene is almost transparent. The emergence of Zeeman spin-splitting effects in optoelectronic properties of phosphorene is pleasant to make it a great potential candidate for logic applications.
Noninvasive diffusion magnetic resonance imaging of brain tumour cell size for the early detection of therapeutic response
Authors: Roberts Thomas A. , Hyare Harpreet , Agliardi Giulia , Hipwell Ben , d’Esposito Angela , Ianus Andrada , Breen-Norris James O. , Ramasawmy Rajiv , Taylor Valerie , Atkinson David , Punwani Shonit , Lythgoe Mark F. , Siow Bernard , Brandner Sebastian , Rees Jeremy , Panagiotaki Eleftheria , Alexander Daniel C. , Walker-Samuel Simon 
Published: June 2020

AbstractCancer cells differ in size from those of their host tissue and are known to change in size during the processes of cell death. A noninvasive method for monitoring cell size would be highly advantageous as a potential biomarker of malignancy and early therapeutic response. This need is particularly acute in brain tumours where biopsy is a highly invasive procedure. Here, diffusion MRI data were acquired in a GL261 glioma mouse model before and during treatment with Temozolomide. The biophysical model VERDICT (Vascular Extracellular and Restricted Diffusion for Cytometry in Tumours) was applied to the MRI data to quantify multi-compartmental parameters connected to the underlying tissue microstructure, which could potentially be useful clinical biomarkers. These parameters were compared to ADC and kurtosis diffusion models, and, measures from histology and optical projection tomography. MRI data was also acquired in patients to assess the feasibility of applying VERDICT in a range of different glioma subtypes. In the GL261 gliomas, cellular changes were detected according to the VERDICT model in advance of gross tumour volume changes as well as ADC and kurtosis models. VERDICT parameters in glioblastoma patients were most consistent with the GL261 mouse model, whilst displaying additional regions of localised tissue heterogeneity. The present VERDICT model was less appropriate for modelling more diffuse astrocytomas and oligodendrogliomas, but could be tuned to improve the representation of these tumour types. Biophysical modelling of the diffusion MRI signal permits monitoring of brain tumours without invasive intervention. VERDICT responds to microstructural changes induced by chemotherapy, is feasible within clinical scan times and could provide useful biomarkers of treatment response.