bluuebunny/crossref_metadata_2025 huggingface dataset:
Confronting Vitruvius: a geometric framework and design methodology for Roman rectangular temples
Authors: Fuchs Wladek
Published: October 2020

Studies of design principles of Roman temples typically have been based on Vitruvius, which inspired a belief that the colonnade was at the core of the geometric framework of every temple and that the lower column diameter (D) was used as a module to plan all other aspects, both horizontally and vertically. Archaeological evidence, however, shows that most extant temples do not match the Vitruvian model.1 Scholars have tried to explain the discrepancies in different ways: for example, by claiming that Vitruvius did not describe the actual state of Roman architecture but “what it should be”,2 that architects had to make “adjustments” to the “Vitruvian ideal” to create a particular effect, or that they had to make on-site corrections.3 A few studies have shown that also other design principles must have been at play. P. Barresi, based on the geometric analyses of several temple-podia of the 5th to 1st c. B.C. in central Italy, argued that they were designed and built relative to a square grid.4 He derived the size of each grid-module from the proportions of the rectangles of the temples' bases. He later reached the same conclusion for the temples of the Capitolium at Sufetula,5 while J.-N. Bonneville presented a similar theory for temples at Baelo Claudia.6 M. Wilson Jones observed that the principal parts of the façades of the Temple of Portunus at Rome and the Maison Carrée at Nîmes formed square contours,7 which he considered a reason for the “irregularities” (relative to Vitruvian principles) in the intercolumniations. He also presented other examples of simple geometric shapes in the compositions of the façades of Roman buildings.
Buildings of faith: Early Christianity in the countryside of the Balearic Islands
Authors: Mas Florit Catalina , Cau Ontiveros Miguel Ángel , Alcaide Silvia
Published: October 2020

The Balearic Islands lie not far off the E coast of the Iberian Peninsula in a strategic position for navigation and trade routes (fig. 1 below). Classical writers considered them two groups of islands: Mallorca and Menorca (with adjacent islands and islets), forming the Baliarides, and Ibiza and Formentera (with other islets), considered the Pityussae.1 In 123 B.C., the Balearides were conquered by the Romans and included first in Hispania Citerior and in Tarraconensis later. The unified archipelago became an independent province at the end of the 4th c., probably due to the re-organization by Theodosius.2 In A.D. 455, the Balearics were conquered by the Vandals, while in 534, Apollinarius, sent by Belisarius, conquered the islands for the Byzantine empire. Theoretically, Byzantine rule lasted until the Islamic conquest of Isam-al-Jalawni in 902-3,3 but it is difficult to draw a precise line for the end of late antiquity on the islands. The Muslim occupation at the very start of the 10th c. witnessed a clear shift. In this paper, we will consider the period from the 5th to the start of the 10th c., even if information for the 8th and 9th c. is scarce.
Briefing a children’s hospice: bridging the evidence gap and redefining value in contemporary healthcare design
Authors: McLaughlan Rebecca , Pert Alan
Published: October 2020

Increasingly, healthcare providers are asking for evidence based design solutions in the construction of new facilities. But where does a designer begin when there is no credible evidence to support the design process because it has yet to gain the attention of researchers? Within this paper we reflect on a university-practice partnership undertaken to provide a feasibility study for the future redevelopment of an eight-bed paediatric hospice in Australia. In embarking on this project, the project team assumed that a thorough literature review would furnish a body of research to rigorously inform the feasibility study. The realisation that this research was not available necessitated an evidence gathering process from first principles, where methods from academic practice required translation and customisation to fit within commercial time frames and resourcing constraints. This article recommends a selection of research methods for use by architects working within healthcare settings where foundational research to inform the design process is not available. It also argues for a re-conceptualisation of the built environment’s value relative to wellbeing.
Lunar Surface Temperature and Emissivity Retrieval From Diviner Lunar Radiometer Experiment Sensor
Authors: Ren Huazhong , Nie Jing , Dong Jiaji , Liu Rongyuan , Fa Wenzhe , Hu Ling , Fan Wenjie
Published: October 2020

The lunar surface temperature (LST) derived from thermal infrared (TIR) measurements can aid in understanding the physical properties of the lunar surface. The Diviner Lunar Radiometer Experiment (herein, Diviner) sensor provides global lunar surface observation in seven TIR channels. However, its retrieval of LST constantly uses a single emissivity value (i.e., 0.95) by ignoring the spatial variation of lunar surface, thereby reducing the accuracy of temperature and day–night temperature difference. To overcome this problem, this study developed a physical method called temperature–emissivity separation (TES) algorithm to retrieve LST and lunar surface emissivity from the daytime observation in three Christiansen Feature (CF) channels (7.55–8.05, 8.10–8.40, and 8.38–8.60 μm) of the Diviner, and then used the emissivity from daytime observation to inverse LST at nighttime observation. Findings showed that the TES algorithm could retrieve LST and emissivity with an error of less than 0.8 K and 0.008, respectively. However, observation noise significantly affected the retrieval accuracy, particularly for the low‐temperature pixels; moreover, high retrieval accuracy requires a surface temperature higher than 240 K. The new algorithm was applied to obtain the daytime and nighttime LST and emissivity from the Diviner images. Results showed that the LST retrieved from the algorithm differed approximately 3.9 K from that calculated from a single emissivity 0.95. Finally, an example of global surface temperature and emissivity were obtained. Consequently, the CF pixels were found to distribute in the latitude range from −60° to 60°; however, they did not have a large distribution in high‐latitude and near‐polar regions.
Toward High Precision XCO2Retrievals From TanSat Observations: Retrieval Improvement and Validation Against TCCON Measurements
Authors: Yang D. , Boesch H. , Liu Y. , Somkuti P. , Cai Z. , Chen X. , Di Noia A. , Lin C. , Lu N. , Lyu D. , Parker R. J. , Tian L. , Wang M. , Webb A. , Yao L. , Yin Z. , Zheng Y. , Deutscher N. M. , Griffith D. W. T. , Hase F. , Kivi R. , Morino I. , Notholt J. , Ohyama H. , Pollard D. F. , Shiomi K. , Sussmann R. , Té Y. , Velazco V. A. , Warneke T. , Wunch D.
Published: October 2020

TanSat is the 1st Chinese carbon dioxide (CO2) measurement satellite, launched in 2016. In this study, the University of Leicester Full Physics (UoL‐FP) algorithm is implemented for TanSat nadir mode XCO2retrievals. We develop a spectrum correction method to reduce the retrieval errors by the online fitting of an 8thorder Fourier series. The spectrum‐correction model and its a priori parameters are developed by analyzing the solar calibration measurement. This correction provides a significant improvement to the O2A band retrieval. Accordingly, we extend the previous TanSat single CO2weak band retrieval to a combined O2A and CO2weak band retrieval. A Genetic Algorithm (GA) has been applied to determine the threshold values of post‐screening filters. In total, 18.3% of the retrieved data is identified as high quality compared to the original measurements. The same quality control parameters have been used in a footprint independent multiple linear regression bias correction due to the strong correlation with the XCO2retrieval error. Twenty sites of the Total Column Carbon Observing Network (TCCON) have been selected to validate our new approach for the TanSat XCO2retrieval. We show that our new approach produces a significant improvement on the XCO2retrieval accuracy and precision when compared to TCCON with an average bias and RMSE of −0.08 ppm and 1.47 ppm, respectively. The methods used in this study can help to improve the XCO2retrieval from TanSat and subsequently the Level‐2 data production, and hence will be applied in the TanSat operational XCO2processing.
Burma Terrane Collision and Northward Indentation in the Eastern Himalayas Recorded in the Eocene‐Miocene Chindwin Basin (Myanmar)
Authors: Westerweel Jan , Licht Alexis , Cogné Nathan , Roperch Pierrick , Dupont‐Nivet Guillaume , Kay Thi Myat , Swe Hnin Hnin , Huang Huasheng , Win Zaw , Wa Aung Day
Published: October 2020

The Burma Terrane (Myanmar) played an important role in the India‐Asia collision and moved over 2,000 km northward on the Indian Plate during the Cenozoic, before colliding with the Asian margin. However, the timing of this collision and its correlation to regional uplift phases, sedimentary provenance, and basin development remain poorly constrained. We report sedimentological, paleomagnetic, and geochronological data from the late Eocene to early Miocene strata of the Chindwin Basin in the Burmese forearc, constraining the paleogeographic evolution of the Burma Terrane and the Eastern Himalayan orogen. Our results highlight two unconformities of late Eocene‐middle Oligocene and latest Oligocene‐early Miocene age, revealing a two‐stage interaction of the Burma Terrane with the Asian margin during its northward translation. The first unconformity follows rapid ~0.6 m/ky subsidence in the Burmese forearc, as shown by magnetostratigraphy. The transition to a fluvial depositional environment and the occurrence of reworked sediments at this first unconformity likely records the commencing collision of India and the northern extent of the Burma Terrane with the Asian margin. The second unconformity shows drastic changes in magnetic properties, mineralogy, and provenance, with high‐grade metamorphic grains and early Miocene apatite U‐Pb and fission‐track ages indicating that it is coeval to a major deformation phase in Myanmar and the Eastern Himalayan orogen. It likely records the indentation of the Burma Terrane into the Eastern Himalayan collision zone, forming the modern Eastern Himalayan Syntaxis.
Pore‐Scale Study of Water Adsorption and Subsequent Methane Transport in Clay in the Presence of Wettability Heterogeneity
Authors: Xu Rui , Prodanović Maša , Landry Christopher
Published: October 2020

Clay minerals are abundant in shale, characterized by a lamellar structure and dimensions smaller than a micron, giving rise to nanometer‐scale pore sizes and large specific surface area. They are commonly associated with water. However, the spatial distribution of the unsaturated water in clay is not very well understood, which significantly affects the subsequent shale gas flow capacity. Wettability heterogeneity in the presence of hydrocarbons further complicates the water distribution in clay. In this study, we use a 3‐D lattice Boltzmann model to study water adsorption and condensation in a reconstructed clay microstructure based on broad‐ion‐beam scanning electron microscopy images. Three wettability conditions are considered including a water‐wet case, a water‐repellent case, and a mixed‐wet case. The spatial distribution of the condensed liquid water phase is visualized, and the connectivity of the remaining open pore spaces is characterized. For the water‐wet case, water preferentially condenses in the small and narrow pore spaces, while the water‐repellent case reports the opposite trend. The mixed‐wet case results in mixed behavior, and connectivity of the pore space is bound by the former two cases. We then study the subsequent methane flow capacity with the presence of water for these three cases, and the calculated methane relative permeability curves show a percolation threshold for the water‐wet case, which is in good agreement with available experimental data in the literature measured on geosynthetic clay liners.
Genetic circuit characterization by inferring RNA polymerase movement and ribosome usage
Authors: Espah Borujeni Amin , Zhang Jing , Doosthosseini Hamid , Nielsen Alec A. K. , Voigt Christopher A.
Published: October 2020

To perform their computational function, genetic circuits change states through a symphony of genetic parts that turn regulator expression on and off. Debugging is frustrated by an inability to characterize parts in the context of the circuit and identify the origins of failures. Here, we take snapshots of a large genetic circuit in different states: RNA-seq is used to visualize circuit function as a changing pattern of RNA polymerase (RNAP) flux along the DNA. Together with ribosome profiling, all 54 genetic parts (promoters, ribozymes, RBSs, terminators) are parameterized and used to inform a mathematical model that can predict circuit performance, dynamics, and robustness. The circuit behaves as designed; however, it is riddled with genetic errors, including cryptic sense/antisense promoters and translation, attenuation, incorrect start codons, and a failed gate. While not impacting the expected Boolean logic, they reduce the prediction accuracy and could lead to failures when the parts are used in other designs. Finally, the cellular power (RNAP and ribosome usage) required to maintain a circuit state is calculated. This work demonstrates the use of a small number of measurements to fully parameterize a regulatory circuit and quantify its impact on host.
Movie viewing elicits rich and reliable brain state dynamics
Authors: Meer Johan N. van der , Breakspear Michael , Chang Luke J. , Sonkusare Saurabh , Cocchi Luca
Published: October 2020

Adaptive brain function requires that sensory impressions of the social and natural milieu are dynamically incorporated into intrinsic brain activity. While dynamic switches between brain states have been well characterised in resting state acquisitions, the remodelling of these state transitions by engagement in naturalistic stimuli remains poorly understood. Here, we show that the temporal dynamics of brain states, as measured in fMRI, are reshaped from predominantly bistable transitions between two relatively indistinct states at rest, toward a sequence of well-defined functional states during movie viewing whose transitions are temporally aligned to specific features of the movie. The expression of these brain states covaries with different physiological states and reflects subjectively rated engagement in the movie. In sum, a data-driven decoding of brain states reveals the distinct reshaping of functional network expression and reliable state transitions that accompany the switch from resting state to perceptual immersion in an ecologically valid sensory experience.
Generation and trapping of a mesoderm biased state of human pluripotency
Authors: Stavish Dylan , Böiers Charlotta , Price Christopher , Frith Thomas J. R. , Halliwell Jason , Saldaña-Guerrero Ingrid , Wray Jason , Brown John , Carr Jonathon , James Chela , Barbaric Ivana , Andrews Peter W. , Enver Tariq
Published: October 2020

We postulate that exit from pluripotency involves intermediates that retain pluripotency while simultaneously exhibiting lineage-bias. Using a MIXL1 reporter, we explore mesoderm lineage-bias within the human pluripotent stem cell compartment. We identify a substate, which at the single cell level coexpresses pluripotent and mesodermal gene expression programmes. Functionally these cells initiate stem cell cultures and exhibit mesodermal bias in differentiation assays. By promoting mesodermal identity through manipulation of WNT signalling while preventing exit from pluripotency using lysophosphatidic acid, we ‘trap’ and maintain cells in a lineage-biased stem cell state through multiple passages. These cells correspond to a normal state on the differentiation trajectory, the plasticity of which is evidenced by their reacquisition of an unbiased state upon removal of differentiation cues. The use of ‘cross-antagonistic’ signalling to trap pluripotent stem cell intermediates with different lineage-bias may have general applicability in the efficient production of cells for regenerative medicine.
Hysteresis of tropical forests in the 21st century
Authors: Staal Arie , Fetzer Ingo , Wang-Erlandsson Lan , Bosmans Joyce H. C. , Dekker Stefan C. , van Nes Egbert H. , Rockström Johan , Tuinenburg Obbe A.
Published: October 2020

Tropical forests modify the conditions they depend on through feedbacks at different spatial scales. These feedbacks shape the hysteresis (history-dependence) of tropical forests, thus controlling their resilience to deforestation and response to climate change. Here, we determine the emergent hysteresis from local-scale tipping points and regional-scale forest-rainfall feedbacks across the tropics under the recent climate and a severe climate-change scenario. By integrating remote sensing, a global hydrological model, and detailed atmospheric moisture tracking simulations, we find that forest-rainfall feedback expands the geographic range of possible forest distributions, especially in the Amazon. The Amazon forest could partially recover from complete deforestation, but may lose that resilience later this century. The Congo forest currently lacks resilience, but is predicted to gain it under climate change, whereas forests in Australasia are resilient under both current and future climates. Our results show how tropical forests shape their own distributions and create the climatic conditions that enable them.
Episodes of fast crystal growth in pegmatites
Authors: Phelps Patrick R. , Lee Cin-Ty A. , Morton Douglas M.
Published: October 2020

Pegmatites are shallow, coarse-grained magmatic intrusions with crystals occasionally approaching meters in length. Compared to their plutonic hosts, pegmatites are thought to have cooled rapidly, suggesting that these large crystals must have grown fast. Growth rates and conditions, however, remain poorly constrained. Here we investigate quartz crystals and their trace element compositions from miarolitic cavities in the Stewart pegmatite in southern California, USA, to quantify crystal growth rates. Trace element concentrations deviate considerably from equilibrium and are best explained by kinetic effects associated with rapid crystal growth. Kinetic crystal growth theory is used to show that crystals accelerated from an initial growth rate of 10−6–10−7 m s−1 to 10−5–10−4 m s−1 (10-100 mm day−1 to 1–10 m day−1), indicating meter sized crystals could have formed within days, if these rates are sustained throughout pegmatite formation. The rapid growth rates require that quartz crystals grew from thin (micron scale) chemical boundary layers at the fluid-crystal interfaces. A strong advective component is required to sustain such thin boundary layers. Turbulent conditions (high Reynolds number) in these miarolitic cavities are shown to exist during crystallization, suggesting that volatile exsolution, crystallization, and cavity generation occur together.
Progression from being at-risk to psychosis: next steps
Authors: Addington Jean , Farris Megan , Devoe Daniel , Metzak Paul
Published: October 2020

Over the past 20 years there has been a great deal of research into those considered to be at risk for developing psychosis. Much has been learned and studies have been encouraging. The aim of this paper is to offer an update of the current status of research on risk for psychosis, and what the next steps might be in examining the progression from CHR to psychosis. Advances have been made in accurate prediction, yet there are some methodological issues in ascertainment, diagnosis, the use of data-driven selection methods and lack of external validation. Although there have been several high-quality treatment trials the heterogeneity of this clinical high-risk population has to be addressed so that their treatment needs can be properly met. Recommendations for the future include more collaborative research programmes, and ensuring they are accessible and harmonized with respect to criteria and outcomes so that the field can continue to move forward with the development of large collaborative consortiums as well as increased funding for multisite projects.
The MARAS dataset, vegetation and soil characteristics of dryland rangelands across Patagonia
Authors: Oliva Gabriel , dos Santos Eder , Sofía Osiris , Umaña Fernando , Massara Virginia , García Martínez Guillermo , Caruso Cecilia , Cariac German , Echevarría Daniela , Fantozzi Anabella , Butti Lucas , Bran Donaldo , Gaitán Juan , Ferrante Daniela , Paredes Paula , Domínguez Erwin , Maestre Fernando T.
Published: October 2020

We present the MARAS (Environmental Monitoring of Arid and Semiarid Regions) dataset, which stores vegetation and soil data of 426 rangeland monitoring plots installed throughout Patagonia, a 624.500 km2 area of southern Argentina and Chile. Data for each monitoring plot includes basic climatic and landscape features, photographs, 500 point intercepts for vegetation cover, plant species list and biodiversity indexes, 50-m line-intercept transect for vegetation spatial pattern analysis, land function indexes drawn from 11 measures of soil surface characteristics and laboratory soil analysis (pH, conductivity, organic matter, N and texture). Monitoring plots were installed between 2007 and 2019, and are being reassessed at 5-year intervals (247 have been surveyed twice). The MARAS dataset provides a baseline from which to evaluate the impacts of climate change and changes in land use intensity in Patagonian ecosystems, which collectively constitute one of the world´s largest rangeland areas. This dataset will be of interest to scientists exploring key ecological questions such as biodiversity-ecosystem functioning relationships, plant-soil interactions and climatic controls on ecosystem structure and functioning.
Air pollution emissions from Chinese power plants based on the continuous emission monitoring systems network
Authors: Tang Ling , Xue Xiaoda , Qu Jiabao , Mi Zhifu , Bo Xin , Chang Xiangyu , Wang Shouyang , Li Shibei , Cui Weigeng , Dong Guangxia
Published: October 2020

To meet the growing electricity demand, China’s power generation sector has become an increasingly large source of air pollutants. Specific control policymaking needs an inventory reflecting the overall, heterogeneous, time-varying features of power plant emissions. Due to the lack of comprehensive real measurements, existing inventories rely on average emission factors that suffer from many assumptions and high uncertainty. This study is the first to develop an inventory of particulate matter (PM), SO2 and NOX emissions from power plants using systematic actual measurements monitored by China’s continuous emission monitoring systems (CEMS) network over 96–98% of the total thermal power capacity. With nationwide, source-level, real-time CEMS-monitored data, this study directly estimates emission factors and absolute emissions, avoiding the use of indirect average emission factors, thereby reducing the level of uncertainty. This dataset provides plant-level information on absolute emissions, fuel uses, generating capacities, geographic locations, etc. The dataset facilitates power emission characterization and clean air policy-making, and the CEMS-based estimation method can be employed by other countries seeking to regulate their power emissions.
RETRACTED ARTICLE: Genome assembly and annotation of Meloidogyne enterolobii, an emerging parthenogenetic root-knot nematode
Authors: Koutsovoulos Georgios D. , Poullet Marine , Elashry Abdelnaser , Kozlowski Djampa K. L. , Sallet Erika , Da Rocha Martine , Perfus-Barbeoch Laetitia , Martin-Jimenez Cristina , Frey Juerg Ernst , Ahrens Christian H. , Kiewnick Sebastian , Danchin Etienne G. J.
Published: October 2020

Root-knot nematodes (genus Meloidogyne) are plant parasites causing huge economic loss in the agricultural industry and affecting severely numerous developing countries. Control methods against these plant pests are sparse, the preferred one being the deployment of plant cultivars bearing resistance genes against Meloidogyne species. However, M. enterolobii is not controlled by the resistance genes deployed in the crop plants cultivated in Europe. The recent identification of this species in Europe is thus a major concern. Here, we sequenced the genome of M. enterolobii using short and long-read technologies. The genome assembly spans 240 Mbp with contig N50 size of 143 kbp, enabling high-quality annotations of 59,773 coding genes, 4,068 non-coding genes, and 10,944 transposable elements (spanning 8.7% of the genome). We validated the genome size by flow cytometry and the structure, quality and completeness by bioinformatics metrics. This ensemble of resources will fuel future projects aiming at pinpointing the genome singularities, the origin, diversity, and adaptive potential of this emerging plant pest.
Frequency-dependent circuits anchored in the dorsal and ventral left anterior insula
Authors: Wang Yifeng , Zou Qijun , Ao Yujia , Liu Yang , Ouyang Yujie , Wang Xinqi , Biswal Bharat , Cui Qian , Chen Huafu
Published: October 2020

The hub role of the right anterior insula (AI) has been emphasized in cognitive neurosciences and been demonstrated to be frequency-dependently organized. However, the functional organization of left AI (LAI) has not been systematically investigated. Here we used 100 unrelated datasets from the Human Connectome Project to study the frequency-dependent organization of LAI along slow 6 to slow 1 bands. The broadband functional connectivity of LAI was similar to previous findings. In slow 6-slow 3 bands, both dorsal and ventral seeds in LAI were correlated to the salience network (SN) and language network (LN) and anti-correlated to the default mode network (DMN). However, these seeds were only correlated to the LAI in slow 2-slow 1 bands. These findings indicate that broadband and narrow band functional connections reflect different functional organizations of the LAI. Furthermore, the dorsal seed had a stronger connection with the LN and anti-correlation with DMN while the ventral seed had a stronger connection within the SN in slow 6-slow 3 bands. In slow 2-slow 1 bands, both seeds had stronger connections with themselves. These observations indicate distinctive functional organizations for the two parts of LAI. Significant frequency effect and frequency by seed interaction were also found, suggesting different frequency characteristics of these two seeds. The functional integration and functional segregation of LDAI and LVAI were further supported by their cognitive associations. The frequency- and seed-dependent functional organizations of LAI may enlighten future clinical and cognitive investigations.
Deep learning algorithms out-perform veterinary pathologists in detecting the mitotically most active tumor region
Authors: Aubreville Marc , Bertram Christof A. , Marzahl Christian , Gurtner Corinne , Dettwiler Martina , Schmidt Anja , Bartenschlager Florian , Merz Sophie , Fragoso Marco , Kershaw Olivia , Klopfleisch Robert , Maier Andreas
Published: October 2020

Manual count of mitotic figures, which is determined in the tumor region with the highest mitotic activity, is a key parameter of most tumor grading schemes. It can be, however, strongly dependent on the area selection due to uneven mitotic figure distribution in the tumor section. We aimed to assess the question, how significantly the area selection could impact the mitotic count, which has a known high inter-rater disagreement. On a data set of 32 whole slide images of H&E-stained canine cutaneous mast cell tumor, fully annotated for mitotic figures, we asked eight veterinary pathologists (five board-certified, three in training) to select a field of interest for the mitotic count. To assess the potential difference on the mitotic count, we compared the mitotic count of the selected regions to the overall distribution on the slide. Additionally, we evaluated three deep learning-based methods for the assessment of highest mitotic density: In one approach, the model would directly try to predict the mitotic count for the presented image patches as a regression task. The second method aims at deriving a segmentation mask for mitotic figures, which is then used to obtain a mitotic density. Finally, we evaluated a two-stage object-detection pipeline based on state-of-the-art architectures to identify individual mitotic figures. We found that the predictions by all models were, on average, better than those of the experts. The two-stage object detector performed best and outperformed most of the human pathologists on the majority of tumor cases. The correlation between the predicted and the ground truth mitotic count was also best for this approach (0.963–0.979). Further, we found considerable differences in position selection between pathologists, which could partially explain the high variance that has been reported for the manual mitotic count. To achieve better inter-rater agreement, we propose to use a computer-based area selection for support of the pathologist in the manual mitotic count.
Novel 199 base pair NEFH promoter drives expression in retinal ganglion cells
Authors: Millington-Ward Sophia , Chadderton Naomi , Berkeley Megan , Finnegan Laura K. , Hanlon Killian S. , Carrigan Matthew , Humphries Peter , Kenna Paul F. , Palfi Arpad , Farrar G. Jane
Published: October 2020

Retinal ganglion cells (RGCs) are known to be involved in several ocular disorders, including glaucoma and Leber hereditary optic neuropathy (LHON), and hence represent target cells for gene therapies directed towards these diseases. Restricting gene therapeutics to the target cell type in many situations may be preferable compared to ubiquitous transgene expression, stimulating researchers to identify RGC-specific promoters, particularly promoter sequences that may also be appropriate in size to fit readily into recombinant adeno associated viral (AAV) vectors, the vector of choice for many ocular gene therapies. In the current study we analysed EGFP expression driven by various sequences of the putative human NEFH promoter in order to define sequences required for preferential expression in RGCs. EGFP expression profiles from four different potential NEFH promoter constructs were compared in vivo in mice using retinal histology and mRNA expression analysis. Notably, two efficient promoter sequences, one comprising just 199 bp, are presented in the study.
Design of intrinsically stretchable and highly conductive polymers for fully stretchable electrochromic devices
Authors: Kim Youngno , Park Chanil , Im Soeun , Kim Jung Hyun
Published: October 2020

Stretchable materials are essential for next generation wearable and stretchable electronic devices. Intrinsically stretchable and highly conductive polymers (termed ISHCP) are designed with semi interpenetrating polymer networks (semi-IPN) that enable polymers to be simultaneously applied to transparent electrodes and electrochromic materials. Through a facile method of acid-catalyzed polymer condensation reaction, optimized ISHCP films show the highest electrical conductivity, 1406 S/cm, at a 20% stretched state. Without the blending of any other elastomeric matrix, ISHCP maintains its initial electrical properties under a cyclic stretch-release of over 50% strain. A fully stretchable electrochromic device based on ISHCP is fabricated and shows a performance of 47.7% ∆T and high coloration efficiency of 434.1 cm2/C at 590 nm. The device remains at 45.2% ∆T after 50% strain stretching. A simple patterned electrolyte layer on a stretchable electrochromic device is also realized. The fabricated device, consisting of all-plastic, can be applied by a solution process for large scale production. The ISHCP reveals its potential application in stretchable electrochromic devices and satisfies the requirements for next-generation stretchable electronics.
Three-dimensional optoacoustic imaging of nailfold capillaries in systemic sclerosis and its potential for disease differentiation using deep learning
Authors: Nitkunanantharajah Suhanyaa , Haedicke Katja , Moore Tonia B. , Manning Joanne B. , Dinsdale Graham , Berks Michael , Taylor Christopher , Dickinson Mark R. , Jüstel Dominik , Ntziachristos Vasilis , Herrick Ariane L. , Murray Andrea K.
Published: October 2020

The autoimmune disease systemic sclerosis (SSc) causes microvascular changes that can be easily observed cutaneously at the finger nailfold. Optoacoustic imaging (OAI), a combination of optical and ultrasound imaging, specifically raster-scanning optoacoustic mesoscopy (RSOM), offers a non-invasive high-resolution 3D visualization of capillaries allowing for a better view of microvascular changes and an extraction of volumetric measures. In this study, nailfold capillaries of patients with SSc and healthy controls are imaged and compared with each other for the first time using OAI. The nailfolds of 23 patients with SSc and 19 controls were imaged using RSOM. The acquired images were qualitatively compared to images from state-of-the-art imaging tools for SSc, dermoscopy and high magnification capillaroscopy. The vascular volume in the nailfold capillaries were computed from the RSOM images. The vascular volumes differ significantly between both cohorts (0.216 ± 0.085 mm3 and 0.337 ± 0.110 mm3; p < 0.0005). In addition, an artificial neural network was trained to automatically differentiate nailfold images from both cohorts to further assess whether OAI is sensitive enough to visualize anatomical differences in the capillaries between the two cohorts. Using transfer learning, the model classifies images with an area under the ROC curve of 0.897, and a sensitivity of 0.783 and specificity of 0.895. In conclusion, this study demonstrates the capabilities of RSOM as an imaging tool for SSc and establishes it as a modality that facilitates more in-depth studies into the disease mechanisms and progression.
Age-related decline in motion contrast sensitivity due to lower absorption rate of cones and calculation efficiency
Authors: Braham chaouche Asma , Silvestre Daphné , Trognon Arthur , Arleo Angelo , Allard Rémy
Published: October 2020

Motion perception is affected by healthy aging, which impairs the ability of older adults to perform some daily activities such as driving. The current study investigated the underlying causes of age-related motion contrast sensitivity losses by using an equivalent noise paradigm to decompose motion contrast sensitivity into calculation efficiency, the temporal modulation transfer function (i.e., temporal blur) and 3 sources of internal noise: stochastic absorption of photons by photoreceptors (i.e., photon noise), neural noise occurring at the retinal level (i.e., early noise) and at the cortical level (i.e., late noise). These sources of internal noise can be disentangled because there impacts on motion contrast sensitivity vary differently as a function of luminance intensity. The impact of healthy aging on these factors was evaluated by measuring motion contrast sensitivity of young and older healthy adults at different luminance intensities, temporal frequencies and with/without external noise. The older adults were found to have higher photon noise, which suggests a lower photon absorption rate of cones. When roughly equating the amount of photons being absorbed by the photoreceptors, older adults had lower calculation efficiencies, but no significant aging effect was found on temporal modulation transfer function, early noise and late noise.
Optimal design and manufacture of variable stiffness laminated continuous fiber reinforced composites
Authors: Boddeti Narasimha , Tang Yunlong , Maute Kurt , Rosen David W. , Dunn Martin L.
Published: October 2020

Advanced manufacturing methods like multi-material additive manufacturing are enabling realization of multiscale materials with intricate spatially varying microstructures and thus, material properties. This blurs the boundary between material and structure, paving the way to lighter, stiffer, and stronger structures. Taking advantage of these tunable multiscale materials warrants development of novel design methods that effectively marry the concepts of material and structure. We propose such a design to manufacture workflow and demonstrate it with laminated continuous fiber-reinforced composites that possess variable stiffness enabled by spatially varying microstructure. This contrasts with traditional fiber-reinforced composites which typically have a fixed, homogenous microstructure and thus constant stiffness. The proposed workflow includes three steps: (1) Design automation—efficient synthesis of an optimized multiscale design with microstructure homogenization enabling efficiency, (2) Material compilation—interpretation of the homogenized design lacking specificity in microstructural detail to a manufacturable structure, and (3) Digital manufacturing—automated manufacture of the compiled structure. We adapted multiscale topology optimization, a mesh parametrization-based algorithm and voxel-based multimaterial jetting for these three steps, respectively. We demonstrated that our workflow can be applied to arbitrary 2D or 3D surfaces. We validated the complete workflow with experiments on two simple planar structures; the results agree reasonably well with simulations.
Caveolin 1 is required for axonal outgrowth of motor neurons and affects Xenopus neuromuscular development
Authors: Breuer Marlen , Berger Hanna , Borchers Annette
Published: October 2020

Caveolins are essential structural proteins driving the formation of caveolae, specialized invaginations of the plasma membrane. Loss of Caveolin-1 (Cav1) function in mice causes distinct neurological phenotypes leading to impaired motor control, however, the underlying developmental mechanisms are largely unknown. In this study we find that loss-of-function of Xenopus Cav1 results in a striking swimming defect characterized by paralysis of the morphants. High-resolution imaging of muscle cells revealed aberrant sarcomeric structures with disorganized actin fibers. As cav1 is expressed in motor neurons, but not in muscle cells, the muscular abnormalities are likely a consequence of neuronal defects. Indeed, targeting cav1 Morpholino oligonucleotides to neural tissue, but not muscle tissue, disrupts axonal outgrowth of motor neurons and causes swimming defects. Furthermore, inhibition of voltage-gated sodium channels mimicked the Cav1 loss-of-function phenotype. In addition, analyzing axonal morphology we detect that Cav1 loss-of-function causes excessive filopodia and lamellipodia formation. Using rescue experiments, we show that the Cav1 Y14 phosphorylation site is essential and identify a role of RhoA, Rac1, and Cdc42 signaling in this process. Taken together, these results suggest a previously unrecognized function of Cav1 in muscle development by supporting axonal outgrowth of motor neurons.
Shifting fish distributions in warming sub-Arctic oceans
Authors: Campana Steven E. , Stefánsdóttir Ragnhildur B. , Jakobsdóttir Klara , Sólmundsson Jón
Published: October 2020

The distributional response of marine fishes to climate warming would be expected to be very different than that of homeothermic birds and mammals, due both to more direct thermal effects on poikilothermic fish physiology and on reduced habitat fragmentation. In this study, we use a combination of linear models and graphical tools to quantify three-dimensional distribution shifts in 82 fish species caught in 5390 standardized groundfish survey tows over a 22-year time frame in the highly-productive sub-Arctic waters around Iceland. Over a 1 °C range, temperature significantly modified the distributional centroids of 72% of all fish species, but had relatively little effect on diversity. Most of the geographic shifts were to the northwest, and there was no overall tendency to move to deeper waters. A doubling of species abundance significantly influenced the distribution of 62% of species, but lacked the poleward orientation observed with temperature increases. Stenothermal species, those near their upper or lower thermal limits, and those with restricted spatial ranges were most likely to shift their distribution in response to climate warming, while deepwater species were not. A 2–3 °C warming of marine waters seems likely to produce large-scale changes in the location of many sub-Arctic fisheries.
Non-hematopoietic deficiency of proprotein convertase subtilisin/kexin type 9 deficiency leads to more severe anemia in a murine model of sickle cell disease
Authors: Venugopal J. , Wang J. , Guo C. , Lu H. , Chen Y. E. , Eitzman D. T.
Published: October 2020

Proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency leads to lower cholesterol and is associated with reduced vascular complications in the general population. Cholesterol lowering may also have beneficial effects in sickle cell disease (SCD). The objective of this study was to determine effects of PCSK9 deficiency in a mouse model of SCD. Bone marrow transplantation (BMT) was performed from donor SCD mice to wild-type, PCSK9-deficient, and LDLR-deficient recipients to generate SCD controls (Pcsk9+/+, SCDbmt) with preserved PCSK9 status, SCD mice with deficiency of PCSK9 (Pcsk9−/−, SCDbmt), and SCD mice with deficiency of LDLR (Ldlr−/−, SCDbmt). Although cholesterol levels were lower in Pcsk9−/−, SCDbmt mice compared to Pcsk9+/+, SCDbmt mice, anemia was more severe in Pcsk9−/−, SCDbmt mice. Increased reticulocytosis, enhanced ex vivo erythrocyte sickling, and increased erythrocyte phosphatidylserine exposure was also observed. Livers, spleens, and kidneys contained increased iron in Pcsk9−/−, SCDbmt mice compared to Pcsk9+/+, SCDbmt mice consistent with greater hemolysis. SCD mice with deficiency of LDLR (Ldlr−/−, SCDbmt mice) had similar anemia as Ldlr+/+, SCDbmt mice despite higher serum cholesterol. In conclusion, deficiency of PCSK9 is associated with worsened anemia in SCD mice due to increased hemolysis. These findings may have implications for lipid-lowering strategies in patients with SCD, as well as for potential novel modifiers of anemia severity.
Association of remote imaging photoplethysmography and cutaneous perfusion in volunteers
Authors: Rasche Stefan , Huhle Robert , Junghans Erik , de Abreu Marcelo Gama , Ling Yao , Trumpp Alexander , Zaunseder Sebastian
Published: October 2020

Remote imaging photoplethysmography (iPPG) senses the cardiac pulse in outer skin layers and is responsive to mean arterial pressure and pulse pressure in critically ill patients. Whether iPPG is sufficiently sensitive to monitor cutaneous perfusion is not known. This study aimed at determining the response of iPPG to changes in cutaneous perfusion measured by  Laser speckle imaging (LSI). Thirty-seven volunteers were engaged in a cognitive test known to evoke autonomic nervous activity and a Heat test. Simultaneous measurements of iPPG and LSI were taken at baseline and during cutaneous perfusion challenges. A perfusion index (PI) was calculated to assess iPPG signal strength. The response of iPPG to the challenges and its relation to LSI were determined. PI of iPPG significantly increased in response to autonomic nervous stimuli and to the Heat test by 5.8% (p = 0.005) and 11.1% (p < 0.001), respectively. PI was associated with LSI measures of cutaneous perfusion throughout experiments (p < 0.001). iPPG responses to study task correlated with those of LSI (r = 0.62, p < 0.001) and were comparable among subjects. iPPG is sensitive to autonomic nervous activity in volunteers and is closely associated with cutaneous perfusion.
Asynchronous electric field visualization using an integrated multichannel electro-optic probe
Authors: Hisatake Shintaro , Kamada Junpei , Asano Yuya , Uchida Hirohisa , Tojo Makoto , Oikawa Yoichi , Miyaji Kunio
Published: October 2020

The higher the frequency, the more complex the scattering, diffraction, multiple reflection, and interference that occur in practical applications such as radar-installed vehicles and transmitter-installed mobile modules, etc. Near-field measurement in “real situations” is important for not only investigating the origin of unpredictable field distortions but also maximizing the system performance by optimal placement of antennas, modules, etc. Here, as an alternative to the previous vector-network-analyzer-based measurement, we propose a new asynchronous approach that visualizes the amplitude and phase distributions of electric near-fields three-dimensionally without placing a reference probe at a fixed point or plugging a cable to the RF source to be measured. We demonstrate the visualization of a frequency-modulated continuous wave (FMCW) signal (24 GHz ± 40 MHz, modulation cycle: 2.5 ms), and show that the measured radiation patterns of a standard horn antenna agree well with the simulation results. We also demonstrate a proof-of-concept experiment that imitates a realistic situation of a bumper installed vehicle to show how the bumper alters the radiation patterns of the FMCW radar signal. The technique is based on photonics and enables measuring in the microwave to millimeter-wave range.
A Purkinje image-based system for an assessment of the density and transmittance spectra of the human crystalline lens in vivo
Authors: Eto Taisuke , Teikari Petteri , Najjar Raymond P. , Nishimura Yuki , Motomura Yuki , Kuze Manami , Higuchi Shigekazu
Published: October 2020

A method for rapid and objective assessment of ocular lens density and transmittance is needed for research and clinical practice. The aim of this study was to determine whether the Purkinje image-based technique can be used for objective and accurate quantification of spectral density and transmittance of ocular media (the mainly crystalline lens) in visible light. Twenty-six individuals (10 young, 9 middle-aged and 7 older individuals) participated in this study. Spectral lens density was evaluated by detecting the intensity of the IVth Purkinje image for different wavelengths. Subsequently, optical density index (ODI), the area under the curve in the lens density spectrum, was calculated and ODIs were compared with clinical lens opacification scales assessed subjectively using a slit lamp. Spectral lens transmittance was estimated from the lens density spectrum. Lens densities were higher in the short wavelength region of the visible spectrum across all age groups. ODI was highly correlated with the clinical opacification scale, while lens transmittance decreased with aging. Our results showed that spectral transmittance of the human crystalline lens can be easily estimated from optical density spectra evaluated objectively and rapidly using the Purkinje image-based technique. Our results provide clinicians and scientists with an accurate, rapid and objective technique for quantification of lens transmittance.