bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin-producing organoids engineered from islet and amniotic epithelial cells to treat diabetes
Authors: Lebreton Fanny , Lavallard Vanessa , Bellofatto Kevin , Bonnet Romain , Wassmer Charles H. , Perez Lisa , Kalandadze Vakhtang , Follenzi Antonia , Boulvain Michel , Kerr-Conte Julie , Goodman David J. , Bosco Domenico , Berney Thierry , Berishvili Ekaterine
Published: October 2019

Maintaining long-term euglycemia after intraportal islet transplantation is hampered by the considerable islet loss in the peri-transplant period attributed to inflammation, ischemia and poor angiogenesis. Here, we show that viable and functional islet organoids can be successfully generated from dissociated islet cells (ICs) and human amniotic epithelial cells (hAECs). Incorporation of hAECs into islet organoids markedly enhances engraftment, viability and graft function in a mouse type 1 diabetes model. Our results demonstrate that the integration of hAECs into islet cell organoids has great potential in the development of cell-based therapies for type 1 diabetes. Engineering of functional mini-organs using this strategy will allow the exploration of more favorable implantation sites, and can be expanded to unlimited (stem-cell-derived or xenogeneic) sources of insulin-producing cells.
Interplay between the human gut microbiome and host metabolism
Authors: Visconti Alessia , Le Roy Caroline I. , Rosa Fabio , Rossi Niccolò , Martin Tiphaine C. , Mohney Robert P. , Li Weizhong , de Rinaldis Emanuele , Bell Jordana T. , Venter J. Craig , Nelson Karen E. , Spector Tim D. , Falchi Mario
Published: October 2019

The human gut is inhabited by a complex and metabolically active microbial ecosystem. While many studies focused on the effect of individual microbial taxa on human health, their overall metabolic potential has been under-explored. Using whole-metagenome shotgun sequencing data in 1,004 twins, we first observed that unrelated subjects share, on average, almost double the number of metabolic pathways (82%) than species (43%). Then, using 673 blood and 713 faecal metabolites, we found metabolic pathways to be associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species showed less than 3,000 associations. Finally, we estimated that the microbiome was involved in a dialogue between 71% of faecal, and 15% of blood, metabolites. This study underlines the importance of studying the microbial metabolic potential rather than focusing purely on taxonomy to find therapeutic and diagnostic targets, and provides a unique resource describing the interplay between the microbiome and the systemic and faecal metabolic environments.
Directing isomerization reactions of cumulenes with electric fields
Authors: Zang Yaping , Zou Qi , Fu Tianren , Ng Fay , Fowler Brandon , Yang Jingjing , Li Hexing , Steigerwald Michael L. , Nuckolls Colin , Venkataraman Latha
Published: October 2019

Electric fields have been proposed as having a distinct ability to catalyze chemical reactions through the stabilization of polar or ionic intermediate transition states. Although field-assisted catalysis is being researched, the ability to catalyze reactions in solution using electric fields remains elusive and the understanding of mechanisms of such catalysis is sparse. Here we show that an electric field can catalyze the cis-to-trans isomerization of [3]cumulene derivatives in solution, in a scanning tunneling microscope. We further show that the external electric field can alter the thermodynamics inhibiting the trans-to-cis reverse reaction, endowing the selectivity toward trans isomer. Using density functional theory-based calculations, we find that the applied electric field promotes a zwitterionic resonance form, which ensures a lower energy transition state for the isomerization reaction. The field also stabilizes the trans form, relative to the cis, dictating the cis/trans thermodynamics, driving the equilibrium product exclusively toward the trans.
Single-particle electroluminescence of CsPbBr3 perovskite nanocrystals reveals particle-selective recombination and blinking as key efficiency factors
Authors: Sharma Dharmendar Kumar , Hirata Shuzo , Vacha Martin
Published: October 2019

Halide perovskites nanocrystals (NCs) are being explored as promising materials for optoelectronic applications, such as light-emitting devices or lasers. However, electroluminescence devices prepared from such NCs have long suffered from low efficiency and there has been no systematic study on the nanoscale origin of the poor efficiencies. Here, we use single-particle spectroscopy to compare electroluminescence and photoluminescence on the level of individual NCs of the perovskite CsPbBr3. The NCs form aggregates in a conducting matrix used as an emission layer in an electroluminescence device. In electroluminescence, only a small fraction of the NCs within the aggregate is emitting as a result of efficient charge migration, accumulation and selective recombination on larger NCs, leading to pronounced blinking and decreased efficiency. Under the condition of comparable excitation rates in both electroluminescence and photoluminescence, the intrinsic quantum yield in electroluminescence is on average 0.36 of that in photoluminescence.
Multicomponent fluctuation spectrum at the quantum critical point in CeCu6−xAgx
Authors: Poudel Lekh , Lawrence Jon M. , Wu Liusuo S. , Ehlers Georg , Qiu Yiming , May Andrew F. , Ronning Filip , Lumsden Mark D. , Mandrus David , Christianson Andrew D.
Published: October 2019

Quantum critical points (QCPs) are widely accepted as a source of a diverse set of collective quantum phases of matter. The basic nature of a QCP is manifested in the critical fluctuation spectrum which in turn is determined by the adjacent phases and associated order parameters. Here we show that the critical fluctuation spectrum of CeCu5.8Ag0.2 can not be explained by fluctuations associated with a single wave vector. Interestingly, when the critical fluctuations at wave vectors corresponding to the incommensurate antiferromagnetic order adjacent to the QCP are separated they are found to be three dimensional and to obey the scaling behavior expected for long wavelength fluctuations near an itinerant antiferromagnetic QCP. Without this separation, E/T scaling with a fractional exponent is observed. Together these results demonstrate that a multicomponent fluctuation spectrum is a previously unexplored route to obtaining E/T scaling at a QCP.
Solution structure of the autophagy-related protein LC3C reveals a polyproline II motif on a mobile tether with phosphorylation site
Authors: Krichel Carsten , Möckel Christina , Schillinger Oliver , Huesgen Pitter F. , Sticht Heinrich , Strodel Birgit , Weiergräber Oliver H. , Willbold Dieter , Neudecker Philipp
Published: October 2019

(Macro-)autophagy is a compartmental degradation pathway conserved from yeast to mammals. The yeast protein Atg8 mediates membrane tethering/hemifusion and cargo recruitment and is essential for autophagy. The human MAP1LC3/GABARAP family proteins show high sequence identity with Atg8, but MAP1LC3C is distinguished by a conspicuous amino-terminal extension with unknown functional significance. We have determined the high-resolution three-dimensional structure and measured the backbone dynamics of MAP1LC3C by NMR spectroscopy. From Ser18 to Ala120, MAP1LC3C forms an α-helix followed by the ubiquitin-like tertiary fold with two hydrophobic binding pockets used by MAP1LC3/GABARAP proteins to recognize targets presenting LC3-interacting regions (LIRs). Unlike other MAP1LC3/GABARAP proteins, the amino-terminal region of MAP1LC3C does not form a stable helix α1 but a “sticky arm” consisting of a polyproline II motif on a flexible linker. Ser18 at the interface between this linker and the structural core can be phosphorylated in vitro by protein kinase A, which causes additional conformational heterogeneity as monitored by NMR spectroscopy and molecular dynamics simulations, including changes in the LIR-binding interface. Based on these results we propose that the amino-terminal polyproline II motif mediates specific interactions with the microtubule cytoskeleton and that Ser18 phosphorylation modulates the interplay of MAP1LC3C with its various target proteins.
Gram-negative synergy and mechanism of action of alkynyl bisbenzimidazoles
Authors: Chamberlin Jordan , Story Sandra , Ranjan Nihar , Chesser Geoffrey , Arya Dev P.
Published: October 2019

Bisbenzimidazoles with terminal alkynyl linkers, selective inhibitors of bacterial topoisomerase I, have been evaluated using bacterial cytological profiling (BCP) to ascertain their mechanism of action and screened for synergism to improve Gram-negative bacterial coverage. Principal component analysis of high throughput fluorescence images suggests a dual-mechanism of action affecting DNA synthesis and cell membrane integrity. Fluorescence microscopy of bacteria challenged with two of the alkynyl-benzimidazoles revealed changes in the cellular ultrastructure that differed from topoisomerase II inhibitors including induction of spheroplasts and membrane lysis. The cytoskeleton recruitment enzyme inhibitor A22 in combination with one of the alkynyl-benzimidazoles was synergistic against Acinetobacter baumannii and Escherichia coli. Gram-positive coverage remained unchanged in the A22-alkynyl bisbenzimidazole combination. Efflux inhibitors were not synergistic, suggesting that the Gram-negative outer membrane was a significant barrier for alkynyl-bisbenzimidazole uptake. Time-kill assays demonstrated the A22-bisbenzimidazole combination had a similar growth inhibition curve to that of norfloxacin in E.coli. Bisbenzimidazoles with terminal alkynyl linkers likely impede bacterial growth by compromising cell membrane integrity and by interfering with DNA synthesis against Gram-positive pathogens and in the synergistic combination against Gram-negative pathogens including E. coli and multidrug-resistant A. baumanii.
Use of Natural Language Processing to identify Obsessive Compulsive Symptoms in patients with schizophrenia, schizoaffective disorder or bipolar disorder
Authors: Chandran David , Robbins Deborah Ahn , Chang Chin-Kuo , Shetty Hitesh , Sanyal Jyoti , Downs Johnny , Fok Marcella , Ball Michael , Jackson Richard , Stewart Robert , Cohen Hannah , Vermeulen Jentien M. , Schirmbeck Frederike , de Haan Lieuwe , Hayes Richard
Published: October 2019

Obsessive and Compulsive Symptoms (OCS) or Obsessive Compulsive Disorder (OCD) in the context of schizophrenia or related disorders are of clinical importance as these are associated with a range of adverse outcomes. Natural Language Processing (NLP) applied to Electronic Health Records (EHRs) presents an opportunity to create large datasets to facilitate research in this area. This is a challenging endeavour however, because of the wide range of ways in which these symptoms are recorded, and the overlap of terms used to describe OCS with those used to describe other conditions. We developed an NLP algorithm to extract OCS information from a large mental healthcare EHR data resource at the South London and Maudsley NHS Foundation Trust using its Clinical Record Interactive Search (CRIS) facility. We extracted documents from individuals who had received a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder. These text documents, annotated by human coders, were used for developing and refining the NLP algorithm (600 documents) with an additional set reserved for final validation (300 documents). The developed NLP algorithm utilized a rules-based approach to identify each of symptoms associated with OCS, and then combined them to determine the overall number of instances of OCS. After its implementation, the algorithm was shown to identify OCS with a precision and recall (with 95% confidence intervals) of 0.77 (0.65–0.86) and 0.67 (0.55–0.77) respectively. The development of this application demonstrated the potential to extract complex symptomatic data from mental healthcare EHRs using NLP to facilitate further analyses of these clinical symptoms and their relevance for prognosis and intervention response.
Ferrodraco lentoni gen. et sp. nov., a new ornithocheirid pterosaur from the Winton Formation (Cenomanian–lower Turonian) of Queensland, Australia
Authors: Pentland Adele H. , Poropat Stephen F. , Tischler Travis R. , Sloan Trish , Elliott Robert A. , Elliott Harry A. , Elliott Judy A. , Elliott David A.
Published: October 2019

The Australian pterosaur record is poor by world standards, comprising fewer than 20 fragmentary specimens. Herein, we describe the new genus and species Ferrodraco lentoni gen. et sp. nov., based on the most complete pterosaur specimen ever found in Australia, and the first reported from the Winton Formation (Cenomanian–lower Turonian). The presence of premaxillary and mandibular crests, and spike-shaped teeth with subcircular bases, enable Ferrodraco to be referred to Anhangueria. Ferrodraco can be distinguished from all other anhanguerian pterosaurs based on two dental characters: the first premaxillary and mandibular tooth pairs are small; and the fourth–seventh tooth pairs are smaller than the third and eighth ones. Ferrodraco was included in a phylogenetic analysis of Pterosauria and resolved as the sister taxon to Mythunga camara (upper Albian Toolebuc Formation, Australia), with that clade occupying the most derived position within Ornithocheiridae. Ornithocheirus simus (Albian Cambridge Greensand, England), Coloborhynchus clavirostris (Valanginian Hastings Sands, England), and Tropeognathus mesembrinus (upper Aptian–lower Albian Romualdo Formation, Brazil) were resolved as successive sister taxa, which suggests that ornithocheirids were cosmopolitan during the Albian–Cenomanian. Furthermore, the stratigraphic age of Ferrodraco lentoni (Cenomanian–lower Turonian) implies that anhanguerians might have survived later in Australia than elsewhere.
Cold Atmospheric Plasma and Plasma-Activated Medium Trigger RONS-Based Tumor Cell Apoptosis
Authors: Bauer Georg , Sersenová Dominika , Graves David B. , Machala Zdenko
Published: October 2019

The selective in vitro anti-tumor mechanisms of cold atmospheric plasma (CAP) and plasma-activated media (PAM) follow a sequential multi-step process. The first step involves the formation of primary singlet oxygen (1O2) through the complex interaction between NO2− and H2O2.1O2 then inactivates some membrane-associated catalase molecules on at least a few tumor cells. With some molecules of their protective catalase inactivated, these tumor cells allow locally surviving cell-derived, extracellular H2O2 and ONOO─ to form secondary 1O2. These species continue to inactivate catalase on the originally triggered cells and on adjacent cells. At the site of inactivated catalase, cell-generated H2O2 enters the cell via aquaporins, depletes glutathione and thus abrogates the cell’s protection towards lipid peroxidation. Optimal inactivation of catalase then allows efficient apoptosis induction through the HOCl signaling pathway that is finalized by lipid peroxidation. An identical CAP exposure did not result in apoptosis for nonmalignant cells. A key conclusion from these experiments is that tumor cell-generated RONS play the major role in inactivating protective catalase, depleting glutathione and establishing apoptosis-inducing RONS signaling. CAP or PAM exposure only trigger this response by initially inactivating a small percentage of protective membrane associated catalase molecules on tumor cells.
Cellular reprogramming for successful CNS axon regeneration is driven by a temporally changing cast of transcription factors
Authors: Dhara Sumona P. , Rau Andrea , Flister Michael J. , Recka Nicole M. , Laiosa Michael D. , Auer Paul L. , Udvadia Ava J.
Published: October 2019

In contrast to mammals, adult fish display a remarkable ability to fully regenerate central nervous system (CNS) axons, enabling functional recovery from CNS injury. Both fish and mammals normally undergo a developmental downregulation of axon growth activity as neurons mature. Fish are able to undergo damage-induced “reprogramming” through re-expression of genes necessary for axon growth and guidance, however, the gene regulatory mechanisms remain unknown. Here we present the first comprehensive analysis of gene regulatory reprogramming in zebrafish retinal ganglion cells at specific time points along the axon regeneration continuum from early growth to target re-innervation. Our analyses reveal a regeneration program characterized by sequential activation of stage-specific pathways, regulated by a temporally changing cast of transcription factors that bind to stably accessible DNA regulatory regions. Strikingly, we also find a discrete set of regulatory regions that change in accessibility, consistent with higher-order changes in chromatin organization that mark (1) the beginning of regenerative axon growth in the optic nerve, and (2) the re-establishment of synaptic connections in the brain. Together, these data provide valuable insight into the regulatory logic driving successful vertebrate CNS axon regeneration, revealing key gene regulatory candidates for therapeutic development.
Tradeoffs in hyphal traits determine mycelium architecture in saprobic fungi
Authors: Lehmann Anika , Zheng Weishuang , Soutschek Katharina , Roy Julien , Yurkov Andrey M. , Rillig Matthias C.
Published: October 2019

The fungal mycelium represents the essence of the fungal lifestyle, and understanding how a mycelium is constructed is of fundamental importance in fungal biology and ecology. Previous studies have examined initial developmental patterns or focused on a few strains, often mutants of model species, and frequently grown under non-harmonized growth conditions; these factors currently collectively hamper systematic insights into rules of mycelium architecture. To address this, we here use a broader suite of fungi (31 species including members of the Ascomycota, Basidiomycota and Mucoromycota), all isolated from the same soil, and tested for ten architectural traits under standardized laboratory conditions. We find great variability in traits among the saprobic fungal species, and detect several clear tradeoffs in mycelial architecture, for example between internodal length and hyphal diameter. Within the constraints so identified, we document otherwise great versatility in mycelium architecture in this set of fungi, and there was no evidence of trait ‘syndromes’ as might be expected. Our results point to an important dimension of fungal properties with likely consequences for coexistence within local communities, as well as for functional complementarity (e.g. decomposition, soil aggregation).
Chocolate-based Ink Three-dimensional Printing (Ci3DP)
Authors: Karyappa Rahul , Hashimoto Michinao
Published: October 2019

Recent advances in three-dimensional (3D) printing technology has enabled to shape food in unique and complex 3D shapes. To showcase the capability of 3D food printing, chocolates have been commonly used as printing inks, and 3D printing based on hot-melt extrusion have been demonstrated to model 3D chocolate products. Although hot-melt extrusion of chocolates is simple, the printing requires precise control over the operating temperature in a narrow range. In this work, for the first time, we directly printed chocolate-based inks in its liquid phase using direct ink writing (DIW) 3D printer to model complex 3D shapes without temperature control. We termed this method as chocolate-based ink 3D printing (Ci3DP). The printing inks were prepared by mixing readily available chocolate syrup and paste with cocoa powders at 5 to 25 w/w% to achieve desired rheological properties. High concentrations of cocoa powders in the chocolate-based inks exhibited shear-thinning properties with viscosities ranging from 102to 104 Pa.s; the inks also possessed finite yield stresses at rest. Rheology of the inks was analyzed by quantifying the degree of shear-thinning by fitting the experimental data of shear stress as a function of shear rate to Herschel-Bulkley model. We demonstrated fabrication of 3D models consisting of chocolate syrups and pastes mixed with the concentration of cocoa powders at 10 to 25 w/w%. The same method was extended to fabricate chocolate-based models consisting of multiple type of chocolate-based inks (e.g. semi-solid enclosure and liquid filling). The simplicity and flexibility of Ci3DP offer great potentials in fabricating complex chocolate-based products without temperature control.
Inactivation of Rhizoctonia solani in fertigation water using regenerative in situ electrochemical hypochlorination
Authors: Lévesque Serge , Graham Thomas , Bejan Dorin , Lawson Jamie , Zhang Ping , Dixon Mike
Published: October 2019

The capture and re-use of greenhouse fertigation water is an efficient use of fertilizer and limited water resources, although the practice is not without risk. Plant pathogens and chemical contaminants can build up over successive capture and re-use cycles; if not properly managed they can lead to reduced productivity or crop loss. There are numerous established and emerging water treatment technologies available to treat fertigation water. Electrochemical processes are emerging as effective means for controlling pathogens via in situ regenerative hypochlorination; a process that is demonstrated here to achieve pathogen control in fertigation solutions without leading to the accumulation of potentially phytotoxic free chlorine residuals associated with other chlorination processes. An electrochemical flow cell (EFC) outfitted with ruthenium dioxide (RuO2) dimensionally stable anodes (DSA) was characterized and evaluated for free chlorine production and Rhizoctonia solani inactivation in both irrigation and fertigation solutions. Pathogen inactivation was achieved at low current densities and short residence or cell contact times. Effluent free chlorine concentrations were significantly lower than commonly reported phytotoxic threshold values (approximately 2.5 mg/L) when fertilizer (containing ammonium) was present in the test solution; an effect attributable to reactions associated with breakpoint chlorination, including chloramine formation, as well as the presence of other oxidizable compounds in the fertilizer. Chloride concentrations were stable under the test conditions suggesting that the EFC was operating as a regenerative in situ electrochemical hypochlorination system. No significant changes to macronutrient concentrations were found following passage through the EFC.
How to probe the microscopic onset of irreversibility with ultracold atoms
Authors: Bürkle R. , Vardi A. , Cohen D. , Anglin J. R.
Published: October 2019

The microscopic onset of irreversibility is finally becoming an experimental subject. Recent experiments on microscopic open and even isolated systems have measured statistical properties associated with entropy production, and hysteresis-like phenomena have been seen in cold atom systems with dissipation (i.e. effectively open systems coupled to macroscopic reservoirs). Here we show how experiments on isolated systems of ultracold atoms can show dramatic irreversibility like cooking an egg. In our proposed experiments, a slow forward-and-back parameter sweep will sometimes fail to return the system close to its initial state. This probabilistic hysteresis is due to the same non-adiabatic spreading and ergodic mixing in phase space that explains macroscopic irreversibility, but realized without dynamical chaos; moreover this fundamental mechanism quantitatively determines the probability of return to the initial state as a function of tunable parameters in the proposed experiments. Matching the predicted curve of return probability will be a conclusive experimental demonstration of the microscopic onset of irreversibility.
All-cause child mortality in minority and non-minority areas in Sichuan Province in Western China, 2008–2017
Authors: Zhao Zi-ling , Yao Ming-hong , Zhang Gang , Wu Gong-hua , Zhang Li , Zhang Ju-ying , Ma Xiao
Published: October 2019

This study aimed to evaluate the disparity in the under-five mortality rate (U5MR) between minority and non-minority areas in Sichuan Province in Western China. Data for this study was obtained from the National Health Statistics Survey System. The Cochran-Armitage trend test was used to analyze the time trend of the U5MR. We conducted Poisson regression model to compare the differences of U5MRs between minority and non-minority areas. The U5MR in Sichuan province was reduced by 62.19% from 2008 to 2017, with the minority and non-minority areas reduced by 60.48% and 65.39%, respectively. The under-five mortality risk in minority areas was approximately 1.791 times (95% CI: 1.790–1.793; P < 0.01) that in non-minority areas. The primary cause of death of children under-five years old in minority areas was the respiratory disease, which was significantly higher than that in non-minority areas (P all < 0.01). The U5MR significantly declined both in minority and non-minority areas in Sichuan Province in Western China from 2008 to 2017. However, disparities still existed between minority and non-minority areas. Respiratory diseases were the main causes of death in minority areas and corresponding rates were higher than those in non-minority areas.
Microplastics in gentoo penguins from the Antarctic region
Authors: Bessa Filipa , Ratcliffe Norman , Otero Vanessa , Sobral Paula , Marques João C. , Waluda Claire M. , Trathan Phil N. , Xavier José C.
Published: October 2019

There is growing evidence that microplastic pollution (<5 mm in size) is now present in virtually all marine ecosystems, even in remote areas, such as the Arctic and the Antarctic. Microplastics have been found in water and sediments of the Antarctic but little is known of their ingestion by higher predators and mechanisms of their entry into Antarctic marine food webs. The goal of this study was to assess the occurrence of microplastics in a top predator, the gentoo penguin Pygoscelis papua from the Antarctic region (Bird Island, South Georgia and Signy Island, South Orkney Islands) and hence assess the potential for microplastic transfer through Antarctic marine food webs. To achieve this, the presence of microplastics in scats (as a proof of ingestion) was investigated to assess the viability of a non-invasive approach for microplastic analyses in Antarctic penguins. A total of 80 penguin scats were collected and any microplastics they contained were extracted. A total of 20% of penguin scats from both islands contained microplastics, consisting mainly of fibers and fragments with different sizes and polymer composition (mean abundance of microplastics: 0.23 ± 0.53 items individual−1 scat, comprising seven different polymers), which were lower values than those found for seabirds in other regions worldwide. No significant differences in microplastic numbers in penguin scats between the two regions were detected. These data highlight the need for further assessment of the levels of microplastics in this sensitive region of the planet, specifically studies on temporal trends and potential effects on penguins and other organisms in the Antarctic marine food web.
OCT angiography features associated with macular edema recurrence after intravitreal bevacizumab treatment in branch retinal vein occlusion
Authors: Choi Kwang-Eon , Yun Cheolmin , Cha Jaehyung , Kim Seong-Woo
Published: October 2019

We aimed to evaluate the relationship between the capillary abnormalities including nonperfusion area (NPA) in optical coherence tomography angiography (OCTA) images and the recurrence of macular edema (ME) secondary to branch retinal vein occlusion (BRVO) after intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF; bevacizumab). The records of 40 patients who underwent intravitreal bevacizumab injection for ME secondary to BRVO and had at least six months of follow-up were reviewed. Central retinal thickness (CRT; μm) and macular edema type were evaluated prior to treatment. After ME resolution, nonperfusion areas in the 1 mm (NPA1) and 1–3 mm (NPA3) zones on the Early Treatment Diabetic Retinopathy Study (ETDRS) circle within the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were measured using OCTA images. Furthermore, other microvascular abnormalities in the both SCP and DCP were compared between groups. ME recurred in 25 of 40 (62.5%) eyes. The NPA1 of the SCP and DCP (p = 0.002, 0.004, respectively), NPA3 of the SCP and DCP (p = 0.002, 0.008, respectively), and initial CRT (p = 0.022) differed significantly between eyes with and without ME recurrence. In multivariate logistic regression analyses, the NPA1 of the DCP (OR: 344.718; p = 0.029) and NPA3 of the SCP (OR: 4.072; p = 0.018) were significantly associated with ME recurrence. Other microvascular abnormalities were not significantly different between two groups. The central NPA and parafoveal NPA of the SCP in OCTA images correlated strongly with ME recurrence in BRVO patients after intravitreal anti-VEGF injection.
Preferential Root Tropisms in 2D Wet Granular Media with Structural Inhomogeneities
Authors: Cejas Cesare M. , Hough Lawrence A. , Beaufret Raphaël , Castaing Jean-Christophe , Frétigny Christian , Dreyfus Rémi
Published: October 2019

We investigate certain aspects of the physical mechanisms of root growth in a granular medium and how these roots adapt to changes in water distribution induced by the presence of structural inhomogeneities in the form of solid intrusions. Physical intrusions such as a square rod added into the 2D granular medium maintain robust capillary action, pumping water from the more saturated areas at the bottom of the cell towards the less saturated areas near the top of the cell while the rest of the medium is slowly devoid of water via evaporation. The intrusion induces “preferential tropism” of roots by first generating a humidity gradient that attracts the root to grow towards it. Then it guides the roots and permits them to grow deeper into more saturated regions in the soil. This further allows more efficient access to available water in the deeper sections of the medium thereby resulting to increased plant lifetime.
Smart meta-superconductor MgB2 constructed by the dopant phase of luminescent nanocomposite
Authors: Li Yongbo , Chen Honggang , Wang Mingzhong , Xu Longxuan , Zhao Xiaopeng
Published: October 2019

On the basis of the idea that the injecting energy will improve the conditions for the formation of Cooper pairs, a smart meta-superconductor (SMSC) was prepared by doping luminescent nanocomposite Y2O3:Eu3+/Ag in MgB2. To improve the superconducting transition temperature (TC) of the MgB2-based superconductor, two types of Y2O3:Eu3+/Ag, which has the strong luminescence characteristic, with different sizes were prepared and marked as m-Y2O3:Eu3+/Ag and n-Y2O3:Eu3+/Ag. MgB2 SMSC was prepared through an ex situ process. Results show that when the dopant content was fixed at 2.0 wt.%, the TC of MgB2 SMSC increased initially then decreased with the increase in the Ag content in the dopant. When the Ag content is 5%, the TC of MgB2 SMSC was 37.2–38.0 K, which was similar to that of pure MgB2. Meanwhile, the TC of MgB2 SMSC doped with n-Y2O3:Eu3+/Ag increased initially then decreased basically with the increase in the content of n-Y2O3:Eu3+/Ag, in which the Ag content is fixed at 5%. The TC of MgB2 SMSC doped with 0.5 wt.% n-Y2O3:Eu3+/Ag was 37.6–38.4 K, which was 0.4 K higher than that of pure MgB2. It is thought that the doping luminescent nanocomposite into the superconductor is a new means to improve the TC of SMSC.
Enrichment of hematopoietic stem/progenitor cells in the zebrafish kidney
Authors: Kobayashi Isao , Kondo Mao , Yamamori Shiori , Kobayashi-Sun Jingjing , Taniguchi Makoto , Kanemaru Kaori , Katakura Fumihiko , Traver David
Published: October 2019

Hematopoietic stem cells (HSCs) maintain the entire blood system throughout life and are utilized in therapeutic approaches for blood diseases. Prospective isolation of highly purified HSCs is crucial to understand the molecular mechanisms underlying regulation of HSCs. The zebrafish is an elegant genetic model for the study of hematopoiesis due to its many unique advantages. It has not yet been possible, however, to purify HSCs in adult zebrafish due to a lack of specific HSC markers. Here we show the enrichment of zebrafish HSCs by a combination of two HSC-related transgenes, gata2a:GFP and runx1:mCherry. The double-positive fraction of gata2a:GFP and runx1:mCherry (gata2a+runx1+) was detected at approximately 0.16% in the kidney, the main hematopoietic organ in teleosts. Transcriptome analysis revealed that gata2a+runx1+ cells showed typical molecular signatures of HSCs, including upregulation of gata2b, gfi1aa, runx1t1, pbx1b, and meis1b. Transplantation assays demonstrated that long-term repopulating HSCs were highly enriched within the gata2a+runx1+ fraction. In contrast, colony-forming assays showed that gata2a−runx1+ cells abundantly contain erythroid- and/or myeloid-primed progenitors. Thus, our purification method of HSCs in the zebrafish kidney is useful to identify molecular cues needed to regulate self-renewal and differentiation of HSCs.
p-wave superconductivity in iron-based superconductors
Authors: Talantsev E. F. , Iida K. , Ohmura T. , Matsumoto T. , Crump W. P. , Strickland N. M. , Wimbush S. C. , Ikuta H.
Published: October 2019

The possibility of p-wave pairing in superconductors has been proposed more than five decades ago, but has not yet been convincingly demonstrated. One difficulty is that some p-wave states are thermodynamically indistinguishable from s-wave, while others are very similar to d-wave states. Here we studied the self-field critical current of NdFeAs(O,F) thin films in order to extract absolute values of the London penetration depth, the superconducting energy gap, and the relative jump in specific heat at the superconducting transition temperature, and find that all the deduced physical parameters strongly indicate that NdFeAs(O,F) is a bulk p-wave superconductor. Further investigation revealed that single atomic layer FeSe also shows p-wave pairing. In an attempt to generalize these findings, we re-examined the whole inventory of superfluid density measurements in iron-based superconductors and show quite generally that single-band weak-coupling p-wave superconductivity is exhibited in iron-based superconductors.
Electroosmotic flow driven microfluidic device for bacteria isolation using magnetic microbeads
Authors: Miller Samuel , Weiss Alison A. , Heineman William R. , Banerjee Rupak K.
Published: October 2019

The presence of bacterial pathogens in water can lead to severe complications such as infection and food poisoning. This research proposes a point-of-care electroosmotic flow driven microfluidic device for rapid isolation and detection of E. coli in buffered solution (phosphate buffered saline solution). Fluorescent E. coli bound to magnetic microbeads were driven through the microfluidic device using both constant forward flow and periodic flow switching at concentrations ranging from 2 × 105 to 4 × 107 bacteria/mL. A calibration curve of fluorescent intensity as a function of bacteria concentration was created using both constant and switching flow, showing an increase in captured fluorescent pixel count as concentration increases. In addition, the use of the flow switching resulted in a significant increase in the capture efficiency of E. coli, with capture efficiencies up to 83% ± 8% as compared to the constant flow capture efficiencies (up to 39% ± 11%), with a sample size of 3 µL. These results demonstrate the improved performance associated with the use of the electroosmotic flow switching system in a point-of-care bacterial detection assay.
New method to calculate the dynamic factor–flow velocity in Geomorphologic instantaneous unit hydrograph
Authors: Chen Yingbing , Shi Peng , Ji Xiaomin , Qu Simin , Zhao Lanlan , Dong Fengcheng
Published: October 2019

The determination of characteristic flow velocity is a hydrodynamic problem needs to be solved in the application of geomorphologic instantaneous unit hydrograph (GIUH) for runoff simulation in areas with no or limited data. In this study, 120 watersheds are collected to construct a regression model; 85 of these basins are used for regression analysis, and the 35 remaining basins are utilized to verify the feasibility of the constructed model. Random forest algorithm is applied to screen out important geomorphologic factors from the 16 extracted factors that may affect flow velocity. Multivariate regression is used to establish the numerical relationship between velocity and the selected factors. Sensitivity analysis of each adopted factor in the constructed model is conducted using the LH-OAT method. The rationality and feasibility of the regression model are validated by comparing the flow velocity calculation with a previous approach, which is also calculated based on geomorphological parameters. Subsequently, the runoff simulation based on the GIUH model is evaluated using the proposed technique. Results demonstrate that the proposed formula possesses high fitting accuracy and can be easily used to calculate flow velocity and generate GIUH.
Targeting CDC7 sensitizes resistance melanoma cells to BRAFV600E-specific inhibitor by blocking the CDC7/MCM2-7 pathway
Authors: Gad Shaimaa A. , Ali Hamdy E. A. , Gaballa Rofaida , Abdelsalam Rania M. , Zerfaoui Mourad , Ali Hamed I. , Salama Salwa H. , Kenawy Sanaa A. , Kandil Emad , Abd Elmageed Zakaria Y.
Published: October 2019

Although the utilization of selective BRAFV600E inhibitors is associated with improved overall survival in patients with metastatic melanoma, a growing challenge of drug resistance has  emerged. CDC7 has been shown to be overexpressed and associated with poor prognosis in various cancers including melanoma. Thus, we aimed to elucidate the biological role of CDC7 in promoting Vemurafenib resistance and the anticipated benefits of dual targeting of BRAFV600E and CDC7 in melanoma cells. We performed exosomes-associated microRNA profiling and functional assays to determine the role of CDC7 in drug resistance using Vemurafenib-sensitive and resistant melanoma cells. Our results demonstrated that Vemurafenib-resistant cells exhibited a persistent expression of CDC7 in addition to prolonged activity of MCM2 compared to drug-sensitive cells. Reconstitution of miR-3613-3p in resistant cells downregulated CDC7 expression and reduced the number of colonies. Treatment of cells with low concentrations of CDC7 inhibitor TAK-931 sensitized resistant cells to Vemurafenib and reduced the number of cell colonies. Taken together, CDC7 overexpression and downregulation of miR-3613-3p were associated with Vemurafenib resistance in BRAFV600E- bearing melanoma cells. Dual targeting of CDC7 and BRAFV600E reduced the development of resistance against Vemurafenib. Further studies are warranted to investigate the clinical effect of targeting CDC7 in metastatic melanoma.
Reconstruction of apo A2A receptor activation pathways reveal ligand-competent intermediates and state-dependent cholesterol hotspots
Authors: Lovera Silvia , Cuzzolin Alberto , Kelm Sebastian , De Fabritiis Gianni , Sands Zara A.
Published: October 2019

G-protein coupled receptors (GPCRs) play a pivotal role in transmitting signals at the cellular level. Structural insights can be exploited to support GPCR structure-based drug discovery endeavours. Despite advances in GPCR crystallography, active state structures are scarce. Molecular dynamics (MD) simulations have been used to explore the conformational landscape of GPCRs. Efforts have been made to retrieve active state conformations starting from inactive structures, however to date this has not been possible without using an energy bias. Here, we reconstruct the activation pathways of the apo adenosine receptor (A2A), starting from an inactive conformation, by applying adaptive sampling MD combined with a goal-oriented scoring function. The reconstructed pathways reconcile well with experiments and help deepen our understanding of A2A regulatory mechanisms. Exploration of the apo conformational landscape of A2A reveals the existence of ligand-competent states, active intermediates and state-dependent cholesterol hotspots of relevance for drug discovery. To the best of our knowledge this is the first time an activation process has been elucidated for a GPCR starting from an inactive structure only, using a non-biased MD approach, opening avenues for the study of ligand binding to elusive yet pharmacologically relevant GPCR states.
A model and simulation of the emotional contagion of netizens in the process of rumor refutation
Authors: Zeng Runxi , Zhu Di
Published: October 2019

The emotional contagion of netizens is an important factor that accelerates the spread of rumors, and it is also key to the effectiveness of rumor refutation. Based on the existing emotional model, we improved the method for calculating the emotional value and the transformation rules to simulate how the infection transforms individual emotion to group emotion during rumor refutation. The results show that the cycle and trend of netizen emotional change vary by period, but the final distribution structure presents a relatively stable state. The factors that affect the emotional changes of netizens are mainly objective and subjective aspects, both of which can promote the evolution of emotional contagion. The objective aspect depends on the speed and credibility of the rumor, and the subjective aspect depends on the degree of intimacy between netizens. After rumor refutation, emotions generally change from negative emotions to positive or immune emotions.
Facile Synthesis of Mesoporous α-Fe2O3@g-C3N4-NCs for Efficient Bifunctional Electro-catalytic Activity (OER/ORR)
Authors: Alduhaish Osamah , Ubaidullah Mohd , Al-Enizi Abdullah M. , Alhokbany Norah , Alshehri Saad M. , Ahmed Jahangeer
Published: October 2019

Mesoporous α-iron oxide@graphitized-carbon nitride nanocomposites (α-Fe2O3@g-C3N4-NCs) were synthesized using urea-formaldehyde (UF) resins at 400 °C/2 h. The mesoporous nature of the prepared nanocomposites was observed from electron microscopy and surface area measurements. The electrochemical measurements show the bifunctional nature of mesoporous α-Fe2O3@g-C3N4-NCs in electrolysis of water for oxygen evolution and oxygen reduction reactions (OER/ORR) using 0.5 M KOH. Higher current density of mesoporous α-Fe2O3@g-C3N4-NCs reveals the enhanced electrochemical performance compared to pure Fe2O3 nanoparticles (NPs). The onset potential, over-potential and Tafel slopes of mesoporous α-Fe2O3@g-C3N4-NCs were found lower than that of pure α-Fe2O3-NPs. Rotating disc electrode experiments followed by the K-L equation were used to investigate 4e− redox system. Therefore, the mesoporous α-Fe2O3@g-C3N4-NCs bifunctional electro-catalysts can be considered as potential future low-cost alternatives for Pt/C catalysts, which are currently used in fuel cells.
Widespread brain reorganization perturbs visuomotor coordination in early glaucoma
Authors: Trivedi Vivek , Bang Ji Won , Parra Carlos , Colbert Max K. , O’Connell Caitlin , Arshad Ahmel , Faiq Muneeb A. , Conner Ian P. , Redfern Mark S. , Wollstein Gadi , Schuman Joel S. , Cham Rakie , Chan Kevin C.
Published: October 2019

Glaucoma is the world’s leading cause of irreversible blindness, and falls are a major public health concern in glaucoma patients. Although recent evidence suggests the involvements of the brain toward advanced glaucoma stages, the early brain changes and their clinical and behavioral consequences remain poorly described. This study aims to determine how glaucoma may impair the brain structurally and functionally within and beyond the visual pathway in the early stages, and whether these changes can explain visuomotor impairments in glaucoma. Using multi-parametric magnetic resonance imaging, glaucoma patients presented compromised white matter integrity along the central visual pathway and around the supramarginal gyrus, as well as reduced functional connectivity between the supramarginal gyrus and the visual occipital and superior sensorimotor areas when compared to healthy controls. Furthermore, decreased functional connectivity between the supramarginal gyrus and the visual brain network may negatively impact postural control measured with dynamic posturography in glaucoma patients. Taken together, this study demonstrates that widespread structural and functional brain reorganization is taking place in areas associated with visuomotor coordination in early glaucoma. These results implicate an important central mechanism by which glaucoma patients may be susceptible to visual impairments and increased risk of falls.
A Fast Parameter Identification Framework for Personalized Pharmacokinetics
Authors: Yang Chenxi , Tavassolian Negar , Haddad Wassim M. , Bailey James M. , Gholami Behnood
Published: October 2019

This paper introduces a novel framework for fast parameter identification of personalized pharmacokinetic problems. Given one sample observation of a new subject, the framework predicts the parameters of the subject based on prior knowledge from a pharmacokinetic database. The feasibility of this framework was demonstrated by developing a new algorithm based on the Cluster Newton method, namely the constrained Cluster Newton method, where the initial points of the parameters are constrained by the database. The algorithm was tested with the compartmental model of propofol on a database of 59 subjects. The average overall absolute percentage error based on constrained Cluster Newton method is 12.10% with the threshold approach, and 13.42% with the nearest-neighbor approach. The average computation time of one estimation is 13.10 seconds. Using parallel computing, the average computation time is reduced to 1.54 seconds, achieved with 12 parallel workers. The results suggest that the proposed framework can effectively improve the prediction accuracy of the pharmacokinetic parameters with limited observations in comparison to the conventional methods. Computation cost analyses indicate that the proposed framework can take advantage of parallel computing and provide solutions within practical response times, leading to fast and accurate parameter identification of pharmacokinetic problems.
Quantum control of excitons for reversible heat transfer
Authors: Murphy Conor N. , Eastham Paul R.
Published: October 2019

Lasers, photovoltaics, and thermoelectrically-pumped light emitting diodes are thermodynamic machines which use excitons (electron-hole pairs) as the working medium. The heat transfers in such devices are highly irreversible, leading to low efficiencies. Here we predict that reversible heat transfers between a quantum-dot exciton and its phonon environment can be induced by laser pulses. We calculate the heat transfer when a quantum-dot exciton is driven by a chirped laser pulse. The reversibility of this heat transfer is quantified by the efficiency of a heat engine in which it forms the hot stroke, which we predict to reach 95% of the Carnot limit. This performance is achieved by using the time-dependent laser-dressing of the exciton to control the heat current and exciton temperature. We conclude that reversible heat transfers can be achieved in excitonic thermal machines, allowing substantial improvements in their efficiency.
Nano-analytical characterization of endogenous minerals in healthy placental tissue: mineral distribution, composition and ultrastructure
Authors: Anthis Alexandre H. C. , Tsolaki Elena , Didierlaurent Louis , Staubli Samuel , Zboray Robert , Neels Antonia , Dietrich Dörthe , Manser Pius , Desbiolles Lotus May , Leschka Sebastian , Wildermuth Simon , Lehner Sandro , Chavatte-Palmer Pascale , Jochum Wolfram , Wick Peter , Dommann Alex , Bürki-Turnherr Tina , Fischer Tina , Hornung René , Bertazzo Sergio , Herrmann Inge K.
Published: October 2019

This study reveals distinct characteristics of minerals formed during gestational ageing using nano-analytical characterization, and paves the way for the identification of markers for disease risks based on atypical placental mineral fingerprints.