bluuebunny/crossref_metadata_2025 huggingface dataset:
Positioning for success: building capacity in academic competencies for early-career researchers in sub-Saharan Africa
Authors: Merritt C. , Jack H. , Mangezi W. , Chibanda D. , Abas M.
Published: July 2019

Background.

Capacity building is essential in low- and middle-income countries (LMICs) to address the gap in skills to conduct and implement research. Capacity building must not only include scientific and technical knowledge, but also broader competencies, such as writing, disseminating research and achieving work–life balance. These skills are thought to promote long-term career success for researchers in high-income countries (HICs) but the availability of such training is limited in LMICs.

Methods.

This paper presents the contextualisation and implementation of the Academic Competencies Series (ACES). ACES is an early-career researcher development programme adapted from a UK university. Through consultation between HIC and LMIC partners, an innovative series of 10 workshops was designed covering themes of self-development, engagement and writing skills. ACES formed part of the African Mental Health Research Initiative (AMARI), a multi-national LMIC-led consortium to recruit, train, support and network early-career mental health researchers from four sub-Saharan African countries.

Results.

Of the 10 ACES modules, three were HIC-LMIC co-led, four led by HIC facilitators with LMIC training experience and three led by external consultants from HICs. Six workshops were delivered face to face and four by webinar. Course attendance was over 90% and the delivery cost was approximately US$4500 per researcher trained. Challenges of adaptation, attendance and technical issues are described for the first round of workshops.

Conclusions.

This paper indicates that a skills development series for early-career researchers can be contextualised and implemented in LMIC settings, and is feasible for co-delivery with local partners at relatively low cost.
Turning an invasive hardwood into an asset: Inoculating Ligustrum lucidum logs with a medicinal mushroom, Trametes versicolor, accelerates wood decomposition under field conditions
Authors: O’Donnell Lisa , Moulton Laurel L. , Stack Jimm
Published: July 2019

Glossy privet (Ligustrum lucidumW. T. Aiton) is a highly aggressive tree that has become globally invasive in a wide range of habitats and can quickly form dense thickets, shading and outcompeting native vegetation. Slowly decomposing slash following removal of dense infestations can create additional management challenges, including fire risk concerns, which curtailed planned invasive plant removal projects on certain tracts within the Balcones Canyonlands Preserve near Austin, TX. This prompted a pilot study to explore whether wood-decaying fungi could be used to hasten the recycling ofL. lucidumlogs back into the forest ecosystem. We inoculated 25 freshly cutL. lucidumlogs withTrametes versicolor(Fr.) Pilat at two study sites and monitored the inoculated logs and 5 untreated control logs over a 3-yr period (February 2015 to March 2018). We found that inoculation significantly accelerated wood decay. By the end of our study, 100% of logs with >3 inoculation points were in advanced stages of decay, while only one of the control logs showed noticeable signs of decay. Inoculating logs in the field was easy and suitable for novices, requiring little or no previous experience to achieve successful results. An added benefit of usingT. versicoloris its medicinal properties and potential for bioremediation. We have continued to inoculate logs with comparable success and are integrating them into forest restoration projects. Applied on a larger scale, these wood-decaying fungi have the potential to transform nonnative deadwood from a threat to an asset.
Russian-olive (Elaeagnus angustifolia) genetic diversity in the western United States and implications for biological control
Authors: Gaskin John F. , Andrés Jose A. , Bogdanowicz Steven M. , Guilbault Kimberly R. , Hufbauer Ruth A. , Schaffner Urs , Weyl Philip , Williams Livy
Published: July 2019

Invasions can be genetically diverse, and that diversity may have implications for invasion management in terms of resistance or tolerance to control methods. We analyzed the population genetics of Russian-olive (Elaeagnus angustifoliaL.), an ecologically important and common invasive tree found in many western U.S. riparian areas. We found three cpDNA haplotypes and, using 11 microsatellite loci, identified three genetic clusters in the 460 plants from 46 populations in the western United States. We found high levels of polymorphism in the microsatellites (5 to 15 alleles per locus; 106 alleles total). Our native-range sampling was limited, and we did not find a genetic match for the most common cpDNA invasive haplotype or a strong confirmation of origin for the most common microsatellite genetic cluster. We did not find geographic population structure (isolation by distance) across the U.S. invasion, but we did identify invasive populations that had the most diversity, and we suggest these as choices for initial biological control–release monitoring. Accessions from each genetic cluster, which coarsely represent the range of genetic diversity found in the invasion, are now included in potential classical biological control agent efficacy testing.
Cluster-based feedback control of turbulent post-stall separated flows
Authors: Nair Aditya G. , Yeh Chi-An , Kaiser Eurika , Noack Bernd R. , Brunton Steven L. , Taira Kunihiko
Published: July 2019

We propose a cluster-based control strategy for feedback control of post-stall separated flows over an airfoil. The present approach partitions the flow trajectories (force measurements) into clusters, which correspond to characteristic coarse-grained phases in a low-dimensional feature space. A feedback control law (using blowing/suction actuation) is then sought for each cluster state through iterative evaluation and downhill simplex search to minimize power consumption in aerodynamic flight. The optimized control laws re-route the flow trajectories to the aerodynamically favourable regions in the feature space in a model-free manner. Utilizing a limited number of sensor measurements for both clustering and optimization, these feedback laws were determined in only $O(10)$ iterations. The objective of the present work is not necessarily to suppress flow separation but to minimize the desired cost function to achieve enhanced aerodynamic performance. The present approach is applied to the control of two- and three-dimensional separated flows over a NACA 0012 airfoil in large-eddy simulations at an angle of attack of $9^{\circ }$, Reynolds number $Re=23\,000$ and free-stream Mach number $M_{\infty }=0.3$. The optimized control laws avoid the intermittent occurrence of long-period shedding associated with high-drag clusters, thus lowering the mean drag. The present work aims to address some of the challenges associated with feedback control design for turbulent separated flows at moderate Reynolds number.
ASKAP commissioning observations of the GAMA 23 field
Authors: Leahy Denis A. , Hopkins A. M. , Norris R. P. , Marvil J. , Collier J. D. , Taylor E. N. , Allison J. R. , Anderson C. , Bell M. , Bilicki M. , Bland-Hawthorn J. , Brough S. , Brown M. J. I. , Driver S. , Gurkan G. , Harvey-Smith L. , Heywood I. , Holwerda B. W. , Liske J. , Lopez-Sanchez A. R. , McConnell D. , Moffett A. , Owers M. S. , Pimbblet K. A. , Raja W. , Seymour N. , Voronkov M. A. , Wang L.
Published: July 2019

We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.
Dietary fibre and mortality risk in patients on peritoneal dialysis
Authors: Xu Xiao , Li Ziqian , Chen Yuan , Liu Xihui , Dong Jie
Published: July 2019

Higher fibre intake reduced all-cause and cardiovascular mortality among healthy population, but such data in dialysis patients are limited. We aimed to examine these associations in patients on peritoneal dialysis (PD). This single-centre prospective cohort study enrolled 881 incident PD patients between October 2002 and August 2014. All patients were followed until death, transfer to haemodialysis, renal transplantation or until being censored in June 2018. Demographic data were collected at baseline. Biochemical, dietary and nutrition data were examined at baseline and thereafter at regular intervals to calculate the average values throughout the study. The outcomes were defined as all-cause and cardiovascular death. Cox proportional regression models were applied to explore the relationship between fibre intake and outcomes. Participants with higher fibre intake were more likely to be younger, male and have better residual renal function and serum lipids at baseline. They were prone to maintain better nutrient status, higher blood pressure and lower inflammatory status at baseline and afterwards. Neither baseline nor time-averaged fibre intake did show protective effects on all-cause mortality after multivariate adjustment in the whole cohort. Among non-diabetic PD patients, an independent association between fibre intake and all-cause mortality was found, in which each 1 g/d increase in time-averaged fibre intake correlated to 13 % of reduction in all-cause mortality. We did not observe any benefits of fibre intake in the CVD mortality for both whole cohort and subgroups. The present study revealed that higher dietary fibre intake appeared to have a protective effect on all-cause mortality in non-diabetic PD patients, which suggest that PD patients should be encouraged to eat a diet rich in fibres.
ONNOTMISUNDERSTANDINGOEDIPUS TYRANNOS
Authors: Kovacs David
Published: July 2019

How are we to understand what happens to Oedipus? What or who is the cause of the terrible deeds—predicted by oracles to both Laius and Oedipus—that he has already committed before the play begins and that are revealed in its course? The purpose of the present essay, whose title alludes to a well-known article by E.R. Dodds, is to draw attention to aspects of the play that have been ignored or explained away. To give them their due it will be necessary to take issue with two views of Dodds (one of which he owes to Wilamowitz) that I regard as mistaken. To argue against an article that is more than fifty years old might be thought a pointless exhumation, but Dodds's highly influential formulations, I will argue, have caused what Sophocles wrote to be either overlooked or misconstrued and are still causing misunderstanding in the second decade of the present century. It is time these views were examined critically.
The importance of the classical channel in the impurity transport of optimized stellarators
Authors: Buller S. , Mollén A. , Newton S. L. , Smith H. M. , Pusztai I.
Published: July 2019

In toroidal magnetic confinement devices, such as tokamaks and stellarators, neoclassical transport is usually an order of magnitude larger than its classical counterpart. However, when a high-collisionality species is present in a stellarator optimized for low Pfirsch–Schlüter current, its classical transport can be comparable to the neoclassical transport. In this letter, we compare neoclassical and classical fluxes and transport coefficients calculated for Wendelstein 7-X (W7-X) and Large Helical Device (LHD) cases. In W7-X, we find that the classical transport of a collisional impurity is comparable to the neoclassical transport for all radii, while it is negligible in the LHD cases, except in the vicinity of radii where the neoclassical transport changes sign. In the LHD case, electrostatic potential variations on the flux surface significantly enhance the neoclassical impurity transport, while the classical transport is largely insensitive to this effect in the cases studied.
Fine-tuning arguments and biological design arguments: can the theist have both?
Authors: BALLIVIAN JOEL
Published: July 2019

There are at least two kinds of design arguments for theism: fine-tuning arguments and biological design arguments. Dougherty and Poston (2008) have argued that the success of one requires the failure of the other, and vice versa. The reason is that the success of these arguments hinges on the following crucial probability: the probability that biological life exists somewhere in the universe given that (a) our universe is finely tuned and that (b) biological development is unguided by intelligence. According to Dougherty and Poston, fine-tuning arguments require that the crucial probability is high while biological design arguments require that the crucial probability is low. As a result, at most one of these design arguments can factor into a cumulative case argument for theism. I argue that this is mistaken. Specifically, I show that fine-tuning arguments can succeed even if the crucial probability is low.
Die Stern-Tagebücher
Authors: Hoppe-Graff Siegfried , Kim Hye-On
Published: July 2019

Zusammenfassung. Die vor mehr als 100 Jahren von Clara und William Stern zur Entwicklung ihrer drei Kinder angelegten Tagebücher stellen hinsichtlich der Beobachtungsdauer und Beobachtungsbreite immer noch die umfangreichste Dokumentation des Entwicklungsgeschehens von der Geburt bis zur Pubertät dar. Im ersten Teil unseres Beitrags erläutern wir den biographischen Entstehungskontext sowie den fachlichen und kulturhistorischen Hintergrund des Tagebuchprojektes. Außerdem beschreiben wir die Standards, die sich die Sterns für die Beobachtung und Aufzeichnung der Entwicklung ihrer Kinder gesetzt hatten. Im zweiten Teil rekonstruieren wir auf der Grundlage der sorgfältigen Lektüre der Originaleintragungen die tagtägliche Praxis der Tagebuchführung. Der Vergleich von Anspruch und tatsächlicher Vorgehensweise offenbart, dass die Sterns in vielfacher Hinsicht hinter den selbst gesteckten Maßstäben zurückgeblieben sind. Er zeigt aber auch, dass in der Sekundärliteratur häufig ein idealisiertes Bild der Tagebücher verbreitet wird. Im dritten Teil demonstrieren wir am Beispiel der Neuauswertung der Tagebucheintragungen zum Als ob-Spiel (pretend play), wie ein historisches Dokument Impulse für die aktuelle Forschung geben kann.
Vertical Velocities, Glacial Isostatic Adjustment, and Earth Structure of Northern and Western Alaska Based on Repeat GPS Measurements
Authors: DeGrandpre Kimberly G. , Freymueller Jeffrey T.
Published: July 2019

Glacial isostatic adjustment (GIA), resulting from the Pleistocene loading of the Laurentide and Cordilleran ice sheets, is frequently associated with positive vertical velocities, or uplift. In Northern and Western Alaska, thousands of kilometers from the center of these ice sheets, vertical motion is primarily negative, or subsidence. Previously, no regional Earth structure model has been estimated for these areas using GIA modeling techniques, and the contribution of GIA processes to the observed subsidence signal has not been studied. We compare the vertical motion rates from 54 campaign and continuous GPS sites in Northern and Western Alaska to the predictions of the ICE‐5G and ICE‐6G GIA models, and to a suite of models that vary with four adjustable parameters defining the lithospheric thickness, asthenospheric thickness and viscosity, and upper mantle thickness and viscosity with the ICE‐3G loading model of Tushingham and Peltier (1991, https://doi.org/10.1029/90JB01583). The best overall fit with the ICE‐3G loading model and Earth model parameters were 120‐km lithosphere over a 100‐km asthenosphere with a viscosity of 2.5 × 1019 Pa/s, overlying a 450‐km‐thick upper mantle with a viscosity of 1.5 × 1021 Pa/s. These values are for a fixed lower mantle viscosity of 3 × 1021 Pa/s in a one‐dimensional Earth model that uses a linear Maxwell rheology. The GIA estimates are found to fit the GPS observations well and can be used to more accurately interpolate between measurement sites in a region where there is sparse spatial and temporal coverage of tectonic vertical velocities.
Rapid iceberg calving following removal of tightly packed pro-glacial mélange
Authors: Xie Surui , Dixon Timothy H. , Holland David M. , Voytenko Denis , Vaňková Irena
Published: July 2019

Iceberg calving is a major contributor to Greenland’s ice mass loss. Pro-glacial mélange (a mixture of sea ice, icebergs, and snow) may be tightly packed in the long, narrow fjords that front many marine-terminating glaciers and can reduce calving by buttressing. However, data limitations have hampered a quantitative understanding. We develop a new radar-based approach to estimate time-varying elevations near the mélange-glacier interface, generating a factor of three or more improvement in elevation precision. We apply the technique to Jakobshavn Isbræ, Greenland’s major outlet glacier. Over a one-month period in early summer 2016, the glacier experienced essentially no calving, and was buttressed by an unusually thick mélange wedge that increased in thickness towards the glacier front. The extent and thickness of the wedge gradually decreased, with large-scale calving starting once the mélange mass within 7 km of the glacier front had decreased by >40%.
Satb1 integrates DNA binding site geometry and torsional stress to differentially target nucleosome-dense regions
Authors: Ghosh Rajarshi P. , Shi Quanming , Yang Linfeng , Reddick Michael P. , Nikitina Tatiana , Zhurkin Victor B. , Fordyce Polly , Stasevich Timothy J. , Chang Howard Y. , Greenleaf William J. , Liphardt Jan T.
Published: July 2019

The Satb1 genome organizer regulates multiple cellular and developmental processes. It is not yet clear how Satb1 selects different sets of targets throughout the genome. Here we have used live-cell single molecule imaging and deep sequencing to assess determinants of Satb1 binding-site selectivity. We have found that Satb1 preferentially targets nucleosome-dense regions and can directly bind consensus motifs within nucleosomes. Some genomic regions harbor multiple, regularly spaced Satb1 binding motifs (typical separation ~1 turn of the DNA helix) characterized by highly cooperative binding. The Satb1 homeodomain is dispensable for high affinity binding but is essential for specificity. Finally, we find that Satb1-DNA interactions are mechanosensitive. Increasing negative torsional stress in DNA enhances Satb1 binding and Satb1 stabilizes base unpairing regions against melting by molecular machines. The ability of Satb1 to control diverse biological programs may reflect its ability to combinatorially use multiple site selection criteria.
Rational design of spontaneous reactions for protecting porous lithium electrodes in lithium–sulfur batteries
Authors: Ren Y. X. , Zeng L. , Jiang H. R. , Ruan W. Q. , Chen Q. , Zhao T. S.
Published: July 2019

A rechargeable lithium anode requires a porous structure for a high capacity, and a stable electrode/electrolyte interface against dendrite formation and polysulfide crossover when used in a lithium-sulfur battery. Here, we design two simple steps of spontaneous reactions for protecting porous lithium electrodes. First, a reaction between molten lithium and sulfur-impregnated carbon nanofiber forms a fibrous network with a lithium shell and a carbon core. Second, we coat the surface of this porous lithium electrode with a composite of lithium bismuth alloys and lithium fluoride through another spontaneous reaction between lithium and bismuth trifluoride, solvated with phosphorous pentasulfide, which also polymerizes with lithium sulfide residual in the electrode to form a solid electrolyte layer. This protected porous lithium electrode enables stable operation of a lithium-sulfur battery with a sulfur loading of 10.2 mg cm−2 at 6.0 mA cm−2 for 200 cycles.
Evidence against tetrapod-wide digit identities and for a limited frame shift in bird wings
Authors: Stewart Thomas A. , Liang Cong , Cotney Justin L. , Noonan James P. , Sanger Thomas J. , Wagner Günter P.
Published: July 2019

In crown group tetrapods, individual digits are homologized in relation to a pentadactyl ground plan. However, testing hypotheses of digit homology is challenging because it is unclear whether digits represent distinct and conserved gene regulatory states. Here we show dramatic evolutionary dynamism in the gene expression profiles of digits, challenging the notion that five digits have conserved developmental identities across amniotes. Transcriptomics shows diversity in the patterns of gene expression differentiation of digits, although the anterior-most digit of the pentadactyl limb has a unique, conserved expression profile. Further, we identify a core set of transcription factors that are differentially expressed among the digits of amniote limbs; their spatial expression domains, however, vary between species. In light of these results, we reevaluate the frame shift hypothesis of avian wing evolution and conclude only the identity of the anterior-most digit has shifted position, suggesting a 1,3,4 digit identity in the bird wing.
Structural basis of tubulin detyrosination by VASH2/SVBP heterodimer
Authors: Zhou Chen , Yan Ling , Zhang Wen-hui , Liu Zhu
Published: July 2019

The C-terminus of α-tubulin undergoes a detyrosination/tyrosination cycle and dysregulation of this cycle is associated with cancer and other diseases. The molecular mechanisms of tubulin tyrosination are well studied, however it has remained unknown how tyrosine is cleaved from the tubulin tail. Here, we report the crystal structure of the long-sought detyrosination enzyme, the VASH2/SVBP heterodimer at 2.2 Å resolution and the structure of the tail/VASH2/SVBP complex at 2.5 Å resolution. VASH2 possesses a non-canonical Cys-His-Ser catalytic architecture for tyrosine cleavage. The dynamics of the α1- and α2- helices of VASH2 are related to the insolubility of VASH2. SVBP plays a chaperone-like role by extensively interacting with VASH2 and stabilizing these dynamic helices. A positively charged groove around the catalytic pocket and the α1- and α2- helices of VASH2 targets the tubulin tail for detyrosination. We provide insights into the mechanisms underlying the cycle of tubulin tyrosine cleavage and religation.
A review of oxygen reduction mechanisms for metal-free carbon-based electrocatalysts
Authors: Ma Ruguang , Lin Gaoxin , Zhou Yao , Liu Qian , Zhang Tao , Shan Guangcun , Yang Minghui , Wang Jiacheng
Published: July 2019

The sluggish kinetics of Oxygen Reduction Reaction (ORR) at the cathode in proton exchange membrane fuel cells or metal-air batteries requires highly effective and stable electrocatalysts to boost the reaction. The low abundance and high price of Pt-based electrocatalysts hamper the widespread application of proton exchange membrane fuel cells and metal-air batteries. As promising alternatives, metal-free carbon materials, especially upon doping heteroatoms or creating defects demonstrated excellent ORR activity, which is as efficient as or even superior to commercial platinum on carbon. Significant progress on the development of advanced carbon materials as highly stable and durable catalysts has been achieved, but the catalytic mechanisms of these materials still remain undistinguished. In present review, we summarized the up-to-date progress in the studies of carbon materials, and emphasized on the combination of experiment and theory to clarify the underlying mechanisms of these materials. At last, we proposed the perspectives on the proper strategies of elucidating the mechanisms of carbon materials as electrocatalysts towards ORR.
Multi-component background learning automates signal detection for spectroscopic data
Authors: Ament Sebastian E. , Stein Helge S. , Guevarra Dan , Zhou Lan , Haber Joel A. , Boyd David A. , Umehara Mitsutaro , Gregoire John M. , Gomes Carla P.
Published: July 2019

Automated experimentation has yielded data acquisition rates that supersede human processing capabilities. Artificial Intelligence offers new possibilities for automating data interpretation to generate large, high-quality datasets. Background subtraction is a long-standing challenge, particularly in settings where multiple sources of the background signal coexist, and automatic extraction of signals of interest from measured signals accelerates data interpretation. Herein, we present an unsupervised probabilistic learning approach that analyzes large data collections to identify multiple background sources and establish the probability that any given data point contains a signal of interest. The approach is demonstrated on X-ray diffraction and Raman spectroscopy data and is suitable to any type of data where the signal of interest is a positive addition to the background signals. While the model can incorporate prior knowledge, it does not require knowledge of the signals since the shapes of the background signals, the noise levels, and the signal of interest are simultaneously learned via a probabilistic matrix factorization framework. Automated identification of interpretable signals by unsupervised probabilistic learning avoids the injection of human bias and expedites signal extraction in large datasets, a transformative capability with many applications in the physical sciences and beyond.
Association between the clinical features of and types of temporomandibular joint ankylosis based on a modified classification system
Authors: Xia Long , An Jingang , He Yang , Xiao E. , Chen Shuo , Yan Yingbin , Zhang Yi
Published: July 2019

This study aimed to describe the clinical features of different types of traumatic temporomandibular joint (TMJ) ankylosis. Seventy-one patients with 102 ankylosed joints were retrospectively reviewed and categorized into four groups according to the grades of severity: type I, non-bony ankylosis of the joint with almost-normal joint space; type II, lateral bony ankylosis marked by a normal joint space that coexists with a radiolucent line; type III, complete bony ankylosis of the joint characterized by only a radiolucent line; and type IV, extensive bony ankylosis without any radiolucent line. The period of ankylosis, maximal mouth opening (MMO), rate of complications, and histopathological changes were compared among groups. Intergroup comparison showed significant differences in the clinical features of MMO and the incidence of complications (p < 0.05). Younger trauma patients tended to develop more severe types of ankylosis than older patients. Additionally, long post-trauma periods were related to the development of severe ankylosis. MMO was highly negatively correlated with the severity of ankylosis. Significant differences were noted among the four types of ankylosis. Younger trauma patients with long post-trauma periods tended to develop more severe TMJ ankylosis, experience more complications, and face more challenges in treatment than older patients.
Angiogenesis and tissue formation driven by an arteriovenous loop in the mouse
Authors: Wong Richard , Donno Roberto , Leon-Valdivieso Christopher Y. , Roostalu Urmas , Derby Brian , Tirelli Nicola , Wong Jason K.
Published: July 2019

The rapid vascularisation of biomaterials and artificial tissues is a key determinant for their in vivo viability and ultimately for their integration in a host; therefore promoting angiogenesis and maintaining the newly formed vascular beds has become a major goal of tissue engineering. The arteriovenous loop (AVL) has been an extensively studied platform which integrates microsurgery with cells scaffolds and growth factors to form neotissues. Most AVL studies to date are limited to larger animal models, which are surgically easier to perform, but have inherent limits for the understanding and interrogation of the underlying in vivo mechanisms due the paucity of transgenic models. Here, we demonstrate for the first time in a mouse model the utility of the AVL in the de novo production of vascularized tissue. We also present the combined use of the model with 3D printed chambers, which allow us to dictate size and shape of the tissues formed. This novel platform will allow for an understanding of the fundamental mechanisms involved in tissue generation de novo.
Tubulin response to intense nanosecond-scale electric field in molecular dynamics simulation
Authors: Marracino Paolo , Havelka Daniel , Průša Jiří , Liberti Micaela , Tuszynski Jack , Ayoub Ahmed T. , Apollonio Francesca , Cifra Michal
Published: July 2019

Intense pulsed electric fields are known to act at the cell membrane level and are already being exploited in biomedical and biotechnological applications. However, it is not clear if electric pulses within biomedically-attainable parameters could directly influence intra-cellular components such as cytoskeletal proteins. If so, a molecular mechanism of action could be uncovered for therapeutic applications of such electric fields. To help clarify this question, we first identified that a tubulin heterodimer is a natural biological target for intense electric fields due to its exceptional electric properties and crucial roles played in cell division. Using molecular dynamics simulations, we then demonstrated that an intense - yet experimentally attainable - electric field of nanosecond duration can affect the bβ-tubulin’s C-terminus conformations and also influence local electrostatic properties at the GTPase as well as the binding sites of major tubulin drugs site. Our results suggest that intense nanosecond electric pulses could be used for physical modulation of microtubule dynamics. Since a nanosecond pulsed electric field can penetrate the tissues and cellular membranes due to its broadband spectrum, our results are also potentially significant for the development of new therapeutic protocols.
Analysis of Water Coupling in Inelastic Neutron Spectra of Uranyl Fluoride
Authors: Miskowiec Andrew , Niedziela J. L. , Kirkegaard Marie C. , Shields Ashley E.
Published: July 2019

Inelastic neutron scattering (INS) is uniquely sensitive to hydrogen due to its comparatively large thermal neutron scattering cross-section (82 b). Consequently, the inclusion of water in real samples presents significant challenges to INS data analysis due directly to the scattering strength of hydrogen. Here, we investigate uranyl fluoride (UO2F2) with inelastic neutron scattering. UO2F2 is the hydrolysis product of uranium hexafluoride (UF6), and is a hygroscopic, uranyl-ion containing particulate. Raman spectral signatures are commonly used for inferential understanding of the chemical environment for the uranyl ion in UO2F2, but no direct measurement of the influence of absorbed water molecules on the overall lattice dynamics has been performed until now. To deconvolute the influence of waters on the observed INS spectra, we use density functional theory with full spectral modeling to separate lattice motion from water coupling. In particular, we present a careful and novel analysis of the Q-dependent Debye–Waller factor, allowing us to separate spectral contributions by mass, which reveals preferential water coupling to the uranyl stretching vibrations. Coupled with the detailed partial phonon densities of states calculated via DFT, we infer the probable adsorption locations of interlayer waters. We explain that a common spectral feature in Raman spectra of uranyl fluoride originates from the interaction of water molecules with the uranyl ion based on this analysis. The Debye–Waller analysis is applicable to all INS spectra and could be used to identify light element contributions in other systems.
Pan-Renal Cell Carcinoma classification and survival prediction from histopathology images using deep learning
Authors: Tabibu Sairam , Vinod P. K. , Jawahar C. V.
Published: July 2019

Histopathological images contain morphological markers of disease progression that have diagnostic and predictive values. In this study, we demonstrate how deep learning framework can be used for an automatic classification of Renal Cell Carcinoma (RCC) subtypes, and for identification of features that predict survival outcome from digital histopathological images. Convolutional neural networks (CNN’s) trained on whole-slide images distinguish clear cell and chromophobe RCC from normal tissue with a classification accuracy of 93.39% and 87.34%, respectively. Further, a CNN trained to distinguish clear cell, chromophobe and papillary RCC achieves a classification accuracy of 94.07%. Here, we introduced a novel support vector machine-based method that helped to break the multi-class classification task into multiple binary classification tasks which not only improved the performance of the model but also helped to deal with data imbalance. Finally, we extracted the morphological features from high probability tumor regions identified by the CNN to predict patient survival outcome of most common clear cell RCC. The generated risk index based on both tumor shape and nuclei features are significantly associated with patient survival outcome. These results highlight that deep learning can play a role in both cancer diagnosis and prognosis.
Study on intracellular delivery of liposome encapsulated quantum dots using advanced fluorescence microscopy
Authors: Bruun Kristina , Hille Carsten
Published: July 2019

Quantum dots increasingly gain popularity for in vivo applications. However, their delivery and accumulation into cells can be challenging and there is still lack of detailed information. Thereby, the application of advanced fluorescence techniques can expand the portfolio of useful parameters for a more comprehensive evaluation. Here, we encapsulated hydrophilic quantum dots into liposomes for studying cellular uptake of these so-called lipodots into living cells. First, we investigated photophysical properties of free quantum dots and lipodots observing changes in the fluorescence decay time and translational diffusion behaviour. In comparison to empty liposomes, lipodots exhibited an altered zeta potential, whereas their hydrodynamic size did not change. Fluorescence lifetime imaging microscopy (FLIM) and fluorescence correlation spectroscopy (FCS), both combined with two-photon excitation (2P), were used to investigate the interaction behaviour of lipodots with an insect epithelial tissue. In contrast to the application of free quantum dots, their successful delivery into the cytosol of salivary gland duct cells could be observed when applying lipodots. Lipodots with different lipid compositions and surface charges did not result in considerable differences in the intracellular labelling pattern, luminescence decay time and diffusion behaviour. However, quantum dot degradation after intracellular accumulation could be assumed from reduced luminescence decay times and blue-shifted luminescence signals. In addition to single diffusing quantum dots, possible intracellular clustering of quantum dots could be assumed from increased diffusion times. Thus, by using a simple and manageable liposome carrier system, 2P-FLIM and 2P-FCS recording protocols could be tested, which are promising for investigating the fate of quantum dots during cellular interaction.
Temperature dependent persistent luminescence: Evaluating the optimum working temperature
Authors: Du Jiaren , De Clercq Olivier Q. , Poelman Dirk
Published: July 2019

Development of persistent luminescent materials has drawn continuous attention in recent years in view of their potential applications in the fields of security night-vision signage, in vivo bio-imaging and optical data storage. Currently, the normative evaluation of a new persistent luminescent material is focused on the light emission spectrum, the afterglow decay curve and the total duration time of the persistent luminescence. In this paper, we investigate the temperature dependent persistent luminescence in some well-known persistent phosphors and relate this to their thermoluminescence properties. The concept of the optimum working temperature is proposed as a new means for evaluating persistent phosphors. It is shown that there is a clear relation between the efficient temperature range of the afterglow output and the thermoluminescence glow curve. The experimental work is supported by simulations of thermoluminescence and afterglow characteristics. The concept of the optimum working temperature for persistent phosphors can be used as an evaluative criterion for applications in various working environments.
Studying hydrogen bonding and dynamics of the acetylate groups of the Special Pair of Rhodobacter sphaeroides WT
Authors: Gräsing Daniel , Dziubińska-Kühn Katarzyna M. , Zahn Stefan , Alia A. , Matysik Jörg
Published: July 2019

Although the cofactors in the bacterial reaction centre of Rhodobacter sphaeroides wild type (WT) are arranged almost symmetrically in two branches, the light-induced electron transfer occurs selectively in one branch. As origin of this functional symmetry break, a hydrogen bond between the acetyl group of PL in the primary donor and His-L168 has been discussed. In this study, we investigate the existence and rigidity of this hydrogen bond with solid-state photo-CIDNP MAS NMR methods offering information on the local electronic structure due to highly sensitive and selective NMR experiments. On the time scale of the experiment, the hydrogen bond between PL and His-L168 appears to be stable and not to be affected by illumination confirming a structural asymmetry within the Special Pair.
Distinct epigenetic profiles in children with perinatally-acquired HIV on antiretroviral therapy
Authors: Shiau Stephanie , Strehlau Renate , Wang Shuang , Violari Avy , Do Catherine , Patel Faeezah , Liberty Afaaf , Krupska Izabela , Arpadi Stephen M. , Foca Marc , Coovadia Ashraf , Abrams Elaine J. , Tycko Benjamin , Terry Mary Beth , Kuhn Louise
Published: July 2019

Perinatally-acquired HIV has persistent effects on long-term health outcomes, even after early treatment. We hypothesize that epigenetic indicators, such as DNA methylation, may elucidate cellular processes that explain these effects. Here, we compared DNA methylation profiles in whole blood from 120 HIV-infected children on antiretroviral therapy (ART) and 60 frequency age-matched HIV-uninfected children aged 4–9 years in Johannesburg, South Africa. Using an individual CpG site approach, we found 1,309 differentially-methylated (DM) CpG sites between groups, including 1,271 CpG sites that were hyper-methylated in the HIV-infected group and 38 CpG sites that were hypo-methylated in the HIV-infected group. Six hyper-methylated CpG sites were inEBF4, which codes for a transcription factor involved in B-cell maturation. The top hypomethylated site was in the promoter region ofNLRC5, encoding a transcription factor that regulates major histocompatibility complex (MHC) class I molecule expression. Using a differentially-methylated region (DMR) approach, we found 315 DMRs between groups, including 28 regions encompassing 686 CpG sites on chromosome 6. A large number of the genes identified in both the CpG site and DMR approaches were located in the MHC region on chromosome 6, which plays an important role in the adaptive immune system. This study provides the first evidence that changes in the epigenome are detectable in children with perinatally-acquired HIV infection on suppressive ART started at an early age.
Ancient origins of low lean mass among South Asians and implications for modern type 2 diabetes susceptibility
Authors: Pomeroy Emma , Mushrif-Tripathy Veena , Cole Tim J. , Wells Jonathan C. K. , Stock Jay T.
Published: July 2019

Living South Asians have low lean tissue mass relative to height, which contributes to their elevated type 2 diabetes susceptibility, particularly when accompanied by obesity. While ongoing lifestyle transitions account for rising obesity, the origins of low lean mass remain unclear. We analysed proxies for lean mass and stature among South Asian skeletons spanning the last 11,000 years (n = 197) to investigate the origins of South Asian low lean mass. Compared with a worldwide sample (n = 2,003), South Asian skeletons indicate low lean mass. Stature-adjusted lean mass increased significantly over time in South Asia, but to a very minor extent (0.04 z-score units per 1,000 years, adjusted R2 = 0.01). In contrast stature decreased sharply when agriculture was adopted. Our results indicate that low lean mass has characterised South Asians since at least the early Holocene and may represent long-term climatic adaptation or neutral variation. This phenotype is therefore unlikely to change extensively in the short term, so other strategies to address increasing non-communicable disease rates must be pursued.
Analysis of lncRNA-miRNA-mRNA Interactions in Hyper-proliferative Human Pulmonary Arterial Smooth Muscle Cells
Authors: Chinnappan Mahendran , Gunewardena Sumedha , Chalise Prabhakar , Dhillon Navneet K.
Published: July 2019

We previously reported enhanced proliferation of smooth muscle cells on the combined exposure of HIV proteins and cocaine leading to the development of HIV-pulmonary arterial hypertension. Here, we attempt to comprehensively understand the interactions between long noncoding RNAs (lncRNAs), mRNAs and micro-RNAs (miRNAs) to determine their role in smooth muscle hyperplasia. Differential expression of lncRNAs, mRNAs and miRNAs were obtained by microarray and small-RNA sequencing from HPASMCs treated with and without cocaine and/or HIV-Tat. LncRNA to mRNA associations were conjectured by analyzing their genomic proximity and by interrogating their association to vascular diseases and cancer co-expression patterns reported in the relevant databases. Neuro-active ligand receptor signaling, Ras signaling and PI3-Akt pathway were among the top pathways enriched in either differentially expressed mRNAs or mRNAs associated to lncRNAs. HPASMC with combined exposure to cocaine and Tat (C + T) vs control identified the following top lncRNA-mRNA pairs, ENST00000495536-HOXB13, T216482-CBL, ENST00000602736-GDF7, and, TCONS_00020413-RND1. Many of the down-regulated miRNAs in the HPASMCs treated with C + T were found to be anti-proliferative and targets of up-regulated lncRNAs targeting up-regulated mRNAs, including down-regulation of miR-185, -491 and up-regulation of corresponding ENST00000585387. Specific knock down of the selected lncRNAs highlighted the importance of non-coding RNAs in smooth muscle hyperplasia.
A zebrafish drug screening platform boosts the discovery of novel therapeutics for spinal cord injury in mammals
Authors: Chapela Diana , Sousa Sara , Martins Isaura , Cristóvão Ana Margarida , Pinto Patrícia , Corte-Real Sofia , Saúde Leonor
Published: July 2019

Spinal cord injury (SCI) is a complex condition, with limited therapeutic options, that results in sensory and motor disabilities. To boost discovery of novel therapeutics, we designed a simple and efficient drug screening platform. This innovative approach allows to determine locomotor rescue properties of small molecules in a zebrafish (Danio rerio) larval spinal cord transection model. We validated our screening platform by showing that Riluzole and Minocycline, two molecules that are in clinical trials for SCI, promote rescue of the locomotor function of the transected larvae. Further validation of the platform was obtained through the blind identification of D-Cycloserine, a molecule scheduled to enter phase IV clinical trials for SCI. Importantly, we identified Tranexamic acid and further showed that this molecule maintains its locomotor recovery properties in a rodent female contusion model. Our screening platform, combined with drug repurposing, promises to propel the rapid translation of novel therapeutics to improve SCI recovery in humans.
SMAC, a computational system to link literature, biomedical and expression data
Authors: Pirrò Stefano , Gadaleta Emanuela , Galgani Andrea , Colizzi Vittorio , Chelala Claude
Published: July 2019

High-throughput technologies have produced a large amount of experimental and biomedical data creating an urgent need for comprehensive and automated mining approaches. To meet this need, we developed SMAC (SMart Automatic Classification method): a tool to extract, prioritise, integrate and analyse biomedical and molecular data according to user-defined terms. The robust ranking step performed on Medical Subject Headings (MeSH) ensures that papers are prioritised based on specific user requirements. SMAC then retrieves any related molecular data from the Gene Expression Omnibus and performs a wide range of bioinformatics analyses to extract biological insights. These features make SMAC a robust tool to explore the literature around any biomedical topic. SMAC can easily be customised/expanded and is distributed as a Docker container (https://hub.docker.com/r/hfx320/smac) ready-to-use on Windows, Mac and Linux OS. SMAC’s functionalities have already been adapted and integrated into the Breast Cancer Now Tissue Bank bioinformatics platform and the Pancreatic Expression Database.
Stumbling reactions in hypo and hyper gravity – muscle synergies are robust across different perturbations of human stance during parabolic flights
Authors: Holubarsch Janek , Helm Michael , Ringhof Steffen , Gollhofer Albert , Freyler Kathrin , Ritzmann Ramona
Published: July 2019

The control of bipedal stance and the capacity to regain postural equilibrium after its deterioration in variable gravities are crucial prerequisites for manned space missions. With an emphasize on natural orthograde posture, computational techniques synthesize muscle activation patterns of high complexity to a simple synergy organization. We used nonnegative matrix factorization to identify muscle synergies during postural recovery responses in human and to examine the functional significance of such synergies for hyper-gravity (1.75 g) and hypo-gravity (0.25 g). Electromyographic data were recorded from leg, trunk and arm muscles of five human exposed to five modes of anterior and posterior support surface translations during parabolic flights including transitional g-levels of 0.25, 1 and 1.75 g. Results showed that in 1 g four synergies accounted for 99% of the automatic postural response across all muscles and perturbation directions. Each synergy in 1 g was correlated to the corresponding one in 0.25 and 1.75 g. This study therefore emphasizes the similarity of the synergy organization of postural recovery responses in Earth, hypo- and hyper-gravity conditions, indicating that the muscle synergies and segmental strategies acquired under terrestrial habits are robust and persistent across variable and acute changes in gravity levels.