bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of BiClusO and its comparison with other biclustering algorithms
Authors: Karim Mohammad Bozlul , Kanaya Shigehiko , Altaf-Ul-Amin Md.
Published: October 2019

This paper describes the implementation of biclustering algorithm BiClusO using graphical user interface and different parameters to generate overlapping biclusters from a binary sparse matrix. We compare our algorithm with several other biclustering algorithms in the context of two different types of biological datasets and four synthetic datasets with known embedded biclusters. Biclustering technique is widely used in different fields of studies for analyzing bipartite relationship dataset. Over the past decade, different biclustering algorithms have been proposed by researchers which are mainly used for biological data analysis. The performance of these algorithms differs depending on dataset size, pattern, and property. These issues create difficulties for a researcher to take the right decision for selecting a good biclustering algorithm. Two different scoring methods along with Gene Ontology(GO) term enrichment analysis have been used to measure and compare the performance of our algorithm. Our algorithm shows the best performance over some other well-known biclustering algorithms.
Clinical predictors of delayed engraftment in autologous hematopoietic cell transplant recipients
Authors: Lutfi Forat , Skelton IV William Paul , Wang Yu , Rosenau Emma , Farhadfar Nosha , Murthy Hemant , Cogle Christopher R. , Brown Ranadall , Hiemenz John , Wingard John R. , Norkin Maxim
Published: October 2019

Objective/background:

Clinical predictors of delayed engraftment following autologous hematopoietic cell transplantation (AHCT) are poorly described in the literature. The purpose of this study was to identify pretransplant characteristics contributing to delayed engraftment (DE) following AHCT.

Methods:

A retrospective, single institution study of 1162 consecutive patients undergoing AHCT from January 1996 to August 2016 was studied for DE. DE was defined as platelet count ≤ 50,000/μl, hemoglobin ≤ 8 g/dL, or absolute neutrophil count ≤ 1000/mm3.

Results:

Of the 1162 AHCT recipients, 263 (22.6%) were identified as having DE at 30-days post-AHCT with 80.0% being solely due to delayed platelet engraftment. Patients with Non-Hodgkin lymphoma (NHL) represented 18% of the original cohort, but accounted for 45% of those with DE, whereas multiple myeloma patients represented 59% of the initial cohort, but only 29% of those that had DE. At 3 months post-AHCT, transfusion dependence (p = .0083) prior to AHCT, low-infused CD34+ cell dose < 3 × 106/kg (p = .0012), and low preAHCT platelet count < 150 × 103/μL (p = .0027) were significantly associated with delayed engraftment.

Conclusion:

Transfusion dependence prior to AHCT, pre-AHCT platelet count, and CD34+ cell dose were the strongest predictors of delayed engraftment in patients undergoing AHCT.
Experimental and numerical investigation of a viscoseal: part II
Authors: Mohamed Jarray , Yann Henry , Aurelian Fatu , Dominique Souchet
Published: October 2019

This article, which is published in two parts, describes research that focuses on the analysis – through an experimental study – of the sealing behaviour of a non-contact dynamic sealing device known as a viscoseal (or sometimes called a helical groove seal). Despite its reliability and its advantageous characteristics, compared with other types of sealing devices, the viscoseal is still under-researched because of its complex characteristics. The experimental apparatus used in this work is equipped with two different test cells. The first, made from acrylic glass, is transparent and is used for the visualisation of the liquid–air interface within the viscoseal. The second cell, used for pressure measurement, is composed of bronze. The experimental results are compared with numerical results obtained using the Reynolds model and also with computational fluid dynamics code.
Fladmark + 40: What Have We Learned about a Potential Pacific Coast Peopling of the Americas?
Authors: Braje Todd J. , Erlandson Jon M. , Rick Torben C. , Davis Loren , Dillehay Tom , Fedje Daryl W. , Froese Duane , Gusick Amy , Mackie Quentin , McLaren Duncan , Pitblado Bonnie , Raff Jennifer , Reeder-Myers Leslie , Waters Michael R.
Published: October 2019

Forty years ago, Knut Fladmark (1979) argued that the Pacific Coast offered a viable alternative to the ice-free corridor model for the initial peopling of the Americas—one of the first to support a “coastal migration theory” that remained marginal for decades. Today, the pre-Clovis occupation at the Monte Verde site is widely accepted, several other pre-Clovis sites are well documented, investigations of terminal Pleistocene subaerial and submerged Pacific Coast landscapes have increased, and multiple lines of evidence are helping decode the nature of early human dispersals into the Americas. Misconceptions remain, however, about the state of knowledge, productivity, and deglaciation chronology of Pleistocene coastlines and possible technological connections around the Pacific Rim. We review current evidence for several significant clusters of early Pacific Coast archaeological sites in North and South America that include sites as old or older than Clovis. We argue that stemmed points, foliate points, and crescents (lunates) found around the Pacific Rim may corroborate genomic studies that support an early Pacific Coast dispersal route into the Americas. Still, much remains to be learned about the Pleistocene colonization of the Americas, and multiple working hypotheses are warranted.
Market Channel Procurement Strategy and School Meal Costs in Farm-to-School Programs
Authors: Fitzsimmons Jill , O'Hara Jeffrey K.
Published: October 2019

Farm-to-school (F2S) local food procurement must be cost-effective to be financially sustainable without policy support. We test, among schools participating in F2S programs, whether market channel procurement strategies for local foods affect schools’ perceptions of whether meal costs decline as a result of F2S participation. Schools that buy local foods exclusively from intermediaries are 7 percentage points less likely to report lower costs from undertaking F2S initiatives. We further demonstrate that the probability that schools source local foods exclusively from intermediaries is influenced by the number of direct marketing farmers in their county.
Silence and Attunement in Legal Performance
Authors: Mulcahy Sean
Published: October 2019

Whilst the law maintains a right to silence, the sensorial and performative dimensions of that silence are seldom considered. This paper adopts an interdisciplinary approach, informed by legal theory and scholarship in the performing arts, such as theatre, performance studies, and music, as a way of understanding how silence plays in the court. The paper offers a typology to navigate the interpretation of silence in legal performance—both verbal and environmental—and to frame discussion of silence’s impact on the legal audience. The author concludes that silence is used and experienced in a similar way in legal and theatrical performance, namely as a means of attunement. The paper contributes new insights into the existing scholarship on acoustic jurisprudence and invites listening to the gaps in speech, the pauses, the background noise, and the silence in the court.
Early Maya Ceremonial Architecture at Pacbitun, Belize
Authors: Powis Terry G. , Micheletti George J. , Crow Kaitlin , Skaggs Sheldon , Stanchly Norbert , Cartagena Nicaela , Powis Jeffrey A.
Published: October 2019

The development of Middle Preclassic (900–300 BC) ceremonial architecture is receiving more attention by archaeologists conducting research in the Maya Lowlands. Although a few examples have been partially excavated, there is still a dearth of information on how and why monumental constructions were originally built. This is largely because early structures often lie below several layers of sequential architecture, making them difficult to locate. Even when Middle Preclassic architecture is identified, exposure is often too limited to fully investigate its form and function. A well-preserved and accessible Middle Preclassic platform would be a rare find and could greatly enhance our knowledge and understanding of the subject. At Pacbitun, Cayo District, Belize, such a discovery has been made beneath the artificially raised surface of the main plaza. To make the most of this opportunity, five seasons of excavation worked to expose this massive building in its entirety. In this article, we provide details concerning the structural design of the platform and its abandonment, as well as present potential architectural comparisons. We conclude by reevaluating complexity at Pacbitun.
Enquiry and the Value of Knowledge
Authors: Walker Barney
Published: October 2019

In this paper I challenge the orthodox view of the significance of Platonic value problems. According to this view, such problems are among the central questions of epistemology, and answering them is essential for justifying the status of epistemology as a major branch of philosophical enquiry. I challenge this view by identifying an assumption on which Platonic value problems are based – the value assumption – and considering how this assumption might be resisted. After articulating a line of thought that supports the assumption, I highlight one way of undermining it, which is to deny that we desire knowledge and not just (e.g.) true belief because we prefer knowledge to true belief. I then consider an attempt to undermine the value assumption in this way, inspired by Bernard Williams. I contend that Williams's argument fails, but also that seeing why it fails is instructive for future attempts to resist the value assumption.
A changing cultural climate: Realising the value of artists working in Antarctica
Authors: Jackson Adele
Published: October 2019

The ratification of the Antarctic Treaty established a unique construct for human presence and activity in Antarctica. The designation of the continent for peace and science has inspired and informed the work of artists from across the world. This paper explores relationships between the Treaty and contemporary visual artists’ responses to Antarctica. Using data from interviews with scientists, cultural professionals and exhibition audiences, I explore the value to science and society of artists’ presence in Antarctica. I look at why in the last 2 years the number of artists being supported to work in Antarctica has declined and conclude with some observations on how this downward trend might be addressed.
Mining, analyzing, and modeling text written on mobile devices
Authors: Vertanen K. , Kristensson P.O.
Published: October 2019

We present a method for mining the web for text entered on mobile devices. Using searching, crawling, and parsing techniques, we locate text that can be reliably identified as originating from 300 mobile devices. This includes 341,000 sentences written on iPhones alone. Our data enables a richer understanding of how users type “in the wild” on their mobile devices. We compare text and error characteristics of different device types, such as touchscreen phones, phones with physical keyboards, and tablet computers. Using our mined data, we train language models and evaluate these models on mobile test data. A mixture model trained on our mined data, Twitter, blog, and forum data predicts mobile text better than baseline models. Using phone and smartwatch typing data from 135 users, we demonstrate our models improve the recognition accuracy and word predictions of a state-of-the-art touchscreen virtual keyboard decoder. Finally, we make our language models and mined dataset available to other researchers.
Putting a Price on the Costs of Climate Related Health Impacts
Authors: Balbus John , Limaye Vijay , Knowlton Kim
Published: October 2019

Using examples from the year 2012, a new study estimates the health costs of deaths and illnesses associated with climate-sensitive events.
Volcanic Gas Emissions Along the Colombian Arc Segment of the Northern Volcanic Zone (CAS‐NVZ): Implications for volcano monitoring and volatile budget of the Andean Volcanic Belt
Authors: Lages J. , Chacón Z. , Burbano V. , Meza L. , Arellano S. , Liuzzo M. , Giudice G. , Aiuppa A. , Bitetto M. , López C.
Published: October 2019

Studying spatial and temporal trends in volcanic gas compositions and fluxes is crucial both to volcano monitoring and to constrain the origin and recycling efficiency of volatiles at active convergent margins. New volcanic gas compositions and volatile fluxes are here reported for Nevado del Ruiz, Galeras, and Purace, three of the most persistently degassing volcanoes located in the Colombian Arc Segment of the Northern Volcanic Zone. At Nevado del Ruiz, from 2014 to 2017, plume emissions showed an average molar CO2/ST ratio of 3.9 ± 1.6 (ST is total sulfur, S). Contemporary, fumarolic chemistry at Galeras progressively shifted toward low‐temperature, S‐depleted fumarolic gas discharges with an average CO2/ST ratio in excess of 10 (6.0–46.0, 2014–2017). This shift in volcanic gas compositions was accompanied by a concurrent decrease in SO2 emissions, confirmed on 21 March 2017 by high‐resolution ultraviolet camera‐based SO2 fluxes of ~2.5 kg/s (~213 t/day). For comparison, SO2 emissions remained high at Nevado del Ruiz (weighted average of 8 kg/s) between 2014 and 2017, while Puracé maintained rather low emission levels (<1 kg/s of SO2, CO2/SO2 ≈ 14). We here estimate carbon dioxide fluxes for Nevado del Ruiz, Galeras, and Puracé of ~23, 30, and 1 kg/s, respectively. These, combined with recent CO2 flux estimates for Nevado del Huila of ~10 kg/s (~860 t/day), imply that this arc segment contributes about 50% to the total subaerial CO2 budget of the Andean Volcanic Belt. Furthermore, our work highlights the northward increase in carbon‐rich sediment input into the mantle wedge via slab fluids and melts that is reflected in magmatic CO2/ST values far higher than those reported for Southern Volcanic Zone and Central Volcanic Zone volcanoes. We estimate that about 20% (~1.3 Mt C/year) of the C being subducted (~6.19 Mt C/year) gets resurfaced through subaerial volcanic gas emissions in Colombia (Nevado del Ruiz ~0.7 Mt C/year). As global volcanic volatile fluxes continue to be quantified and refined, the contribution from this arc segment should not be underestimated.
On the Delayed Coupling Between Ocean and Atmosphere in Recent Weak El Niño Episodes
Authors: Johnson N. C. , L'Heureux M. L. , Chang C.‐H. , Hu Z.‐Z.
Published: October 2019

The recent borderline El Niño events of 2014/2015 and 2018/2019 provided operational centers with unique challenges because of the apparent absence of typical coupling between the tropical atmosphere and ocean before onset. The mismatch between atmosphere and ocean raises questions about its causes and predictability. Here we analyze observational data since 1979 to show that a sea surface temperature pattern characterized by an anomalous gradient in the western and central equatorial Pacific played a critical role in inhibiting the expected onset of central tropical Pacific deep convection during these events. This sea surface temperature pattern, which produces an atmospheric response that opposes the response to elevated eastern Pacific sea surface temperatures, has become more prevalent over the past 40 years.
Differences in Eastern North Pacific Stratification and Their Potential Impact on the Depth of Winter Mixing in CMIP5 Models
Authors: Old P. , Hautala S. L. , Thompson L.
Published: October 2019

Upper ocean stratification is known to play an important role in the seasonal evolution of the ocean mixed layer depth. This study examines biases in climatological upper ocean stratification in the Coupled Model Intercomparison Project version 5 historical simulations in the North Pacific. To quantify the potential impact of these stratification differences on the depth of winter mixing in two regions (the eastern subarctic and subtropical gyres), regionally averaged August stratification profiles were advanced to March using common atmospheric forcing fields and a single‐column mixed layer model. This approach is supported by correlation between the climate models' March mixed layer depth fields and those predicted by the one‐dimensional model. Substantial observation/model and model/model differences in predicted winter mixed layer depth have broad implications for how the climate models regulate the ocean‐atmosphere interactions that set thermocline water properties and impact nutrient supply to the upper ocean.
Improving Estimates of Gross Primary Productivity by Assimilating Solar‐Induced Fluorescence Satellite Retrievals in a Terrestrial Biosphere Model Using a Process‐Based SIF Model
Authors: Bacour C. , Maignan F. , MacBean N. , Porcar‐Castell A. , Flexas J. , Frankenberg C. , Peylin P. , Chevallier F. , Vuichard N. , Bastrikov V.
Published: October 2019

Over the last few years, solar‐induced chlorophyll fluorescence (SIF) observations from space have emerged as a promising resource for evaluating the spatio‐temporal distribution of gross primary productivity (GPP) simulated by global terrestrial biosphere models. SIF can be used to improve GPP simulations by optimizing critical model parameters through statistical Bayesian data assimilation techniques. A prerequisite is the availability of a functional link between GPP and SIF in terrestrial biosphere models. Here we present the development of a mechanistic SIF observation operator in the ORCHIDEE (Organizing Carbon and Hydrology In Dynamic Ecosystems) terrestrial biosphere model. It simulates the regulation of photosystem II fluorescence quantum yield at the leaf level thanks to a novel parameterization of non‐photochemical quenching as a function of temperature, photosynthetically active radiation, and normalized quantum yield of photochemistry. It emulates the radiative transfer of chlorophyll fluorescence to the top of the canopy using a parametric simplification of the SCOPE (Soil Canopy Observation Photosynthesis Energy) model. We assimilate two years of monthly OCO‐2 (Orbiting Carbon Observatory‐2) SIF product at 0.5° (2015–2016) to optimize ORCHIDEE photosynthesis and phenological parameters over an ensemble of grid points for all plant functional types. The impact on the simulated GPP is considerable with a large decrease of the global scale budget by 28 GtC/year over the period 1990–2009. The optimized GPP budget (134/136 GtC/year over 1990–2009/2001–2009) remarkably agrees with independent GPP estimates, FLUXSAT (137 GtC/year over 2001–2009) in particular and FLUXCOM (121 GtC/year over 1990–2009). Our results also suggest a biome dependency of the SIF‐GPP relationship that needs to be improved for some plant functional types.
A 21st Century View of the March 1989 Magnetic Storm
Authors: Boteler D. H.
Published: October 2019

On 13 March 1989, the largest magnetic storm of the last century caused widespread effects on power systems including a blackout of the Hydro‐Québec system. Since then this event has become the archetypal disturbance for examining the geomagnetic hazard to power systems. However, even 30 years on from 1989, the story of exactly what happened in March 1989 is far from complete. This paper reexamines the information available about the March 1989 event and uses this to construct a timeline and description of the space weather phenomena and how they caused the power system effects. The evidence shows that the disturbance was caused by two coronal mass ejections (CMEs): the first associated with a X4.5 flare on 10 March and the second linked to a M7.3 flare on 12 March. The arrival of the interplanetary CME shock fronts caused storm sudden commencements at 01.27 and 07.43 UT on 13 March. The transit time and speed of the first (second) interplanetary CME shock are 54.5 hr (31.5 hr) and 760 km/s (1,320 km/s). Empirical relations are used to estimate solar wind speed and southward interplanetary magnetic field, Bs, and give values of v = 980 km/s, Bs = 40 to 60 nT at the peak of the storm. Key findings are that the second storm sudden commencement occurred at the same time as the substorm that impacted the Hydro‐Québec system and indicates that external triggering of the substorm may have contributed to a faster substorm onset than might otherwise have occurred. This caused the production of larger geomagnetically induced currents that caused the Hydro‐Québec blackout. The March 1989 storm had the largest recorded value of the Dst index representing the size of the magnetic storm main phase, but the Hydro‐Québec blackout occurred early in the storm when the Dst value was less disturbed. Only later in the storm did Dst reach its peak value. At this time an expansion of the auroral oval brought disturbances to lower latitudes where they caused power system problems in the United States, United Kingdom, and Sweden.
Generation of qualified clinical-grade functional hepatocytes from human embryonic stem cells in chemically defined conditions
Authors: Li Zhongwen , Wu Jun , Wang Lei , Han Weifang , Yu Juan , Liu Xin , Wang Yukai , Zhang Ying , Feng Guihai , Li Wei , Stacey Glyn Nigel , Gu Qi , Hu Baoyang , Wang Liu , Zhou Qi , Hao Jie
Published: October 2019

Hepatocytes have been successfully generated from human pluripotent stem cells (hPSCs). However, the cost-effective and clinical-grade generation of hepatocytes from hPSCs still need to be improved. In this study, we reported the production of functional hepatocytes from clinical-grade human embryonic stem cells (hESCs) under good manufacturing practice (GMP) requirements. We sequentially generated primitive streak (PS), definitive endoderm (DE), hepatoblasts and hepatocyte-like cells (HLCs) from hESCs in the different stages with completely defined reagents. During hepatoblast differentiation, dimethyl sulfoxide (DMSO), transferrin, L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (Vc-Mg), insulin, and sodium selenite were used instead of cytokines and FBS/KOSR. Then, hepatoblasts were differentiated into HLCs that had a typical hepatocyte morphology and possessed characteristics of mature hepatocytes, such as metabolic-related gene expression, albumin secretion, fat accumulation, glycogen storage, and inducible cytochrome P450 activity in vitro. HLCs integrated into the livers of Tet-uPA Rag2–/– Il2rg–/– (URG) mice, which partially recovered after transplantation. Furthermore, a series of biosafety-related experiments were performed to ensure future clinical applications. In conclusion, we developed a chemically defined system to generate qualified clinical-grade HLCs from hESCs under GMP conditions. HLCs have been proven to be safe and effective for treating liver failure. This efficient platform could facilitate the treatment of liver diseases using hESC-derived HLCs transplantation.
In situ-grown compressed NiCo2S4 barrier layer for efficient and durable polysulfide entrapment
Authors: Huang Shaozhuan , Wang Ye , Hu Junping , Von Lim Yew , Kong Dezhi , Guo Lu , Kou Zongkui , Chen Yaxin , Yang Hui Ying
Published: October 2019

Modifying a polypropylene (PP) separator with a polysulfide barrier layer can improve the cycling performance of lithium–sulfur (Li–S) batteries. However, conventional slurry-coating- and vacuum-filtration-designed barriers usually show poor particle connection and require extra binder. Herein, we propose a facile in situ growth method and a subsequent compression strategy to design multifunctional NiCo2S4 (NiCoS) nanosheet arrays on a PP membrane for high-performance Li–S batteries. The in situ grown NiCoS nanosheet arrays are interconnected, conductive and closely adhered to the PP membrane without using any binder. After mechanical compression treatment, the overall NiCoS film is compacted, lightweight (0.148 mg cm−2) and ultrathin (0.8 μm). Density functional theory calculations combined with adsorption and diffusion tests prove that the NiCoS nanosheets have highly efficient physical/chemical entrapping capabilities for preventing polysulfide shuttling. Moreover, in situ electrochemical impedance spectroscopy demonstrated that the NiCoS barrier could efficiently suppress polysulfide diffusion and concurrently facilitate redox reactions. When applying this multifunctional separator, a sulfur/carbon nanotube (S/CNT) cathode with high sulfur content (75 wt%) delivers significantly improved long-term cycling performance, with 0.056% capacity decay per cycle over 500 cycles. This work opens up new opportunities to design multifunctional separators by an in situ growth strategy for high-performance Li–S batteries.
Single-molecule level control of host-guest interactions in metallocycle-C60 complexes
Authors: Tang Jian-Hong , Li Yueqi , Wu Qingqing , Wang Zixiao , Hou Songjun , Tang Kun , Sun Yue , Wang Hui , Wang Heng , Lu Cheng , Wang Xiang , Li Xiaopeng , Wang Dong , Yao Jiannian , Lambert Colin J. , Tao Nongjian , Zhong Yu-Wu , Stang Peter J.
Published: October 2019

Host−guest interactions are of central importance in many biological and chemical processes. However, the investigation of the formation and decomplexation of host−guest systems at the single-molecule level has been a challenging task. Here we show that the single-molecule conductance of organoplatinum(II) metallocycle hosts can be enhanced by an order of magnitude by the incorporation of a C60 guest molecule. Mechanically stretching the metallocycle-C60 junction with a scanning tunneling microscopy break junction technique causes the release of the C60 guest from the metallocycle, and consequently the conductance switches back to the free-host level. Metallocycle hosts with different shapes and cavity sizes show different degrees of flexibility to accommodate the C60 guest in response to mechanical stretching. DFT calculations provide further insights into the electronic structures and charge transport properties of the molecular junctions based on metallocycles and the metallocycle-C60 complexes.
Rational design of crystalline two-dimensional frameworks with highly complicated topological structures
Authors: Liang Rong-Ran , Xu Shun-Qi , Zhang Lei , A Ru-Han , Chen Pohua , Cui Fu-Zhi , Qi Qiao-Yan , Sun Junliang , Zhao Xin
Published: October 2019

Constructing two-dimensional (2D) polymers with complex tessellation patterns via synthetic chemistry makes a significant contribution not only to the understanding of the emergence of complex hierarchical systems in living organisms, but also to the fabrication of advanced hierarchical materials. However, to achieve such tasks is a great challenge. In this communication we report a facile and general approach to tessellate 2D covalent organic frameworks (COFs) by three or four geometric shapes/sizes, which affords 2D COFs bearing three or four different kinds of pores and increases structural complexity in tessellations of 2D polymers to a much higher level. The complex tessellation patterns of the COFs are elucidated by powder X-ray diffraction studies, theoretical simulations and high-resolution TEM.
Thermodynamic control of −1 programmed ribosomal frameshifting
Authors: Bock Lars V. , Caliskan Neva , Korniy Natalia , Peske Frank , Rodnina Marina V. , Grubmüller Helmut
Published: October 2019

mRNA contexts containing a ‘slippery’ sequence and a downstream secondary structure element stall the progression of the ribosome along the mRNA and induce its movement into the −1 reading frame. In this study we build a thermodynamic model based on Bayesian statistics to explain how −1 programmed ribosome frameshifting can work. As training sets for the model, we measured frameshifting efficiencies on 64 dnaX mRNA sequence variants in vitro and also used 21 published in vivo efficiencies. With the obtained free-energy difference between mRNA-tRNA base pairs in the 0 and −1 frames, the frameshifting efficiency of a given sequence can be reproduced and predicted from the tRNA−mRNA base pairing in the two frames. Our results further explain how modifications in the tRNA anticodon modulate frameshifting and show how the ribosome tunes the strength of the base-pair interactions.
Consciousness-specific dynamic interactions of brain integration and functional diversity
Authors: Luppi Andrea I. , Craig Michael M. , Pappas Ioannis , Finoia Paola , Williams Guy B. , Allanson Judith , Pickard John D. , Owen Adrian M. , Naci Lorina , Menon David K. , Stamatakis Emmanuel A.
Published: October 2019

Prominent theories of consciousness emphasise different aspects of neurobiology, such as the integration and diversity of information processing within the brain. Here, we combine graph theory and dynamic functional connectivity to compare resting-state functional MRI data from awake volunteers, propofol-anaesthetised volunteers, and patients with disorders of consciousness, in order to identify consciousness-specific patterns of brain function. We demonstrate that cortical networks are especially affected by loss of consciousness during temporal states of high integration, exhibiting reduced functional diversity and compromised informational capacity, whereas thalamo-cortical functional disconnections emerge during states of higher segregation. Spatially, posterior regions of the brain’s default mode network exhibit reductions in both functional diversity and integration with the rest of the brain during unconsciousness. These results show that human consciousness relies on spatio-temporal interactions between brain integration and functional diversity, whose breakdown may represent a generalisable biomarker of loss of consciousness, with potential relevance for clinical practice.
Climate drivers of the 2017 devastating fires in Portugal
Authors: Turco Marco , Jerez Sonia , Augusto Sofia , Tarín-Carrasco Patricia , Ratola Nuno , Jiménez-Guerrero Pedro , Trigo Ricardo M.
Published: October 2019

A record 500,000 hectares burned in Portugal during the extreme wildfire season of 2017, with more than 120 human lives lost. Here we analyse the climatic factors responsible for the burned area (BA) from June to October series in Portugal for the period 1980–2017. Superposed onto a substantially stationary trend on BA data, strong oscillations on shorter time scales were detected. Here we show that they are significantly affected by the compound effect of summer (June-July-August) drought and high temperature conditions during the fire season. Drought conditions were calculated using the Standardized Precipitation Evapotranspiration Index (SPEI), the Standardized Precipitation Index (SPI) and the Standardized Soil Moisture Index (SSI). Then the extent to which the burned area has diverged from climate-expected trends was assessed. Our results indicate that in the absence of other drivers, climate change would have led to higher BA values. In addition, the 2017 extreme fire season is well captured with the model forced with climate drivers only, suggesting that the extreme fire season of 2017 could be a prelude to future conditions and likewise events. Indeed, the expected further increase of drought and high temperature conditions in forthcoming decades, point at a potential increase of fire risk in this region. The climate-fire model developed in this study could be useful to develop more skilled seasonal predictions capable of anticipating potentially hazardous conditions.
Identification and Visualization of Functionally Important Domains and Residues in Herpes Simplex Virus Glycoprotein K(gK) Using a Combination of Phylogenetics and Protein Modeling
Authors: Rider Paul J. F. , Coghill Lyndon M. , Naderi Misagh , Brown Jeremy M. , Brylinski Michal , Kousoulas Konstantin G.
Published: October 2019

Alphaherpesviruses are a subfamily of herpesviruses that include the significant human pathogens herpes simplex viruses (HSV) and varicella zoster virus (VZV). Glycoprotein K (gK), conserved in all alphaherpesviruses, is a multi-membrane spanning virion glycoprotein essential for virus entry into neuronal axons, virion assembly, and pathogenesis. Despite these critical functions, little is known about which gK domains and residues are most important for maintaining these functions across all alphaherpesviruses. Herein, we employed phylogenetic and structural analyses including the use of a novel model for evolutionary rate variation across residues to predict conserved gK functional domains. We found marked heterogeneity in the evolutionary rate at the level of both individual residues and domains, presumably as a result of varying selective constraints. To clarify the potential role of conserved sequence features, we predicted the structures of several gK orthologs. Congruent with our phylogenetic analysis, slowly evolving residues were identified at potentially structurally significant positions across domains. We found that using a quantitative measure of amino acid rate variation combined with molecular modeling we were able to identify amino acids predicted to be critical for gK protein structure/function. This analysis yields targets for the design of anti-herpesvirus therapeutic strategies across all alphaherpesvirus species that would be absent from more traditional analyses of conservation.
Full-wave electromagnetic modes and hybridization in nanoparticle dimers
Authors: Pascale Mariano , Miano Giovanni , Tricarico Roberto , Forestiere Carlo
Published: October 2019

The plasmon hybridization theory is based on a quasi-electrostatic approximation of the Maxwell’s equations. It does not take into account magnetic interactions, retardation effects, and radiation losses. Magnetic interactions play a dominant role in the scattering from dielectric nanoparticles. The retardation effects play a fundamental role in the coupling of the modes with the incident radiation and in determining their radiative strength; their exclusion may lead to erroneous predictions of the excited modes and of the scattered power spectra. Radiation losses may lead to a significant broadening of the scattering resonances. We propose a hybridization theory for non-Hermitian composite systems based on the full-Maxwell equations that, overcoming all the limitations of the plasmon hybridization theory, unlocks the description of dielectric dimers. As an example, we decompose the scattered field from silicon and silver dimers, under different excitation conditions and gap-sizes, in terms of dimer modes, pinpointing the hybridizing isolated-sphere modes behind them.
Experimental validation of force inference in epithelia from cell to tissue scale
Authors: Kong Weiyuan , Loison Olivier , Chavadimane Shivakumar Pruthvi , Chan Eunice HoYee , Saadaoui Mehdi , Collinet Claudio , Lenne Pierre-François , Clément Raphaël
Published: October 2019

Morphogenesis relies on the active generation of forces, and the transmission of these forces to surrounding cells and tissues. Hence measuring forces directly in developing embryos is an essential task to study the mechanics of development. Among the experimental techniques that have emerged to measure forces in epithelial tissues, force inference is particularly appealing. Indeed it only requires a snapshot of the tissue, as it relies on the topology and geometry of cell contacts, assuming that forces are balanced at each vertex. However, establishing force inference as a reliable technique requires thorough validation in multiple conditions. Here we performed systematic comparisons of force inference with laser ablation experiments in four epithelial tissues from two animals, the fruit fly and the quail. We show that force inference accurately predicts single junction tension, tension patterns in stereotyped groups of cells, and tissue-scale stress patterns, in wild type and mutant conditions. We emphasize its ability to capture the distribution of forces at different scales from a single image, which gives it a critical advantage over perturbative techniques such as laser ablation. Overall, our results demonstrate that force inference is a reliable and efficient method to quantify the mechanical state of epithelia during morphogenesis, especially at larger scales when inferred tensions and pressures are binned into a coarse-grained stress tensor.
Transcriptome analysis suggests a compensatory role of the cofactors coenzyme A and NAD+ in medium-chain acyl-CoA dehydrogenase knockout mice
Authors: Martines Anne-Claire M. F. , Gerding Albert , Stolle Sarah , Vieira-Lara Marcel A. , Wolters Justina C. , Jurdzinski Angelika , Bongiovanni Laura , de Bruin Alain , van der Vlies Pieter , van der Vries Gerben , Bloks Vincent W. , Derks Terry G. J. , Reijngoud Dirk-Jan , Bakker Barbara M.
Published: October 2019

During fasting, mitochondrial fatty-acid β-oxidation (mFAO) is essential for the generation of glucose by the liver. Children with a loss-of-function deficiency in the mFAO enzyme medium-chain acyl-Coenzyme A dehydrogenase (MCAD) are at serious risk of life-threatening low blood glucose levels during fasting in combination with intercurrent disease. However, a subset of these children remains asymptomatic throughout life. In MCAD-deficient (MCAD-KO) mice, glucose levels are similar to those of wild-type (WT) mice, even during fasting. We investigated if metabolic adaptations in the liver may underlie the robustness of this KO mouse. WT and KO mice were given a high- or low-fat diet and subsequently fasted. We analyzed histology, mitochondrial function, targeted mitochondrial proteomics, and transcriptome in liver tissue. Loss of MCAD led to a decreased capacity to oxidize octanoyl-CoA. This was not compensated for by altered protein levels of the short- and long-chain isoenzymes SCAD and LCAD. In the transcriptome, we identified subtle adaptations in the expression of genes encoding enzymes catalyzing CoA- and NAD(P)(H)-involving reactions and of genes involved in detoxification mechanisms. We discuss how these processes may contribute to robustness in MCAD-KO mice and potentially also in asymptomatic human subjects with a complete loss of MCAD activity.
Three-Dimensional Microscopy by Milling with Ultraviolet Excitation
Authors: Guo Jiaming , Artur Camille , Eriksen Jason L. , Mayerich David
Published: October 2019

Analysis of three-dimensional biological samples is critical to understanding tissue function and the mechanisms of disease. Many chronic conditions, like neurodegenerative diseases and cancers, correlate with complex tissue changes that are difficult to explore using two-dimensional histology. While three-dimensional techniques such as confocal and light-sheet microscopy are well-established, they are time consuming, require expensive instrumentation, and are limited to small tissue volumes. Three-dimensional microscopy is therefore impractical in clinical settings and often limited to core facilities at major research institutions. There would be a tremendous benefit to providing clinicians and researchers with the ability to routinely image large three-dimensional tissue volumes at cellular resolution. In this paper, we propose an imaging methodology that enables fast and inexpensive three-dimensional imaging that can be readily integrated into current histology pipelines. This method relies on block-face imaging of paraffin-embedded samples using deep-ultraviolet excitation. The imaged surface is then ablated to reveal the next tissue section for imaging. The final image stack is then aligned and reconstructed to provide tissue models that exceed the depth and resolution achievable with modern three-dimensional imaging systems.
The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma
Authors: Lee A. T. J. , Chew W. , Wilding C. P. , Guljar N. , Smith M. J. , Strauss D. C. , Fisher C. , Hayes A. J. , Judson I. , Thway K. , Jones R. L. , Huang P. H.
Published: October 2019

The characterisation and clinical relevance of tumour-infiltrating lymphocytes (TILs) in leiomyosarcoma (LMS), a subtype of soft tissue sarcoma that exhibits histological heterogeneity, is not established. The use of tissue microarrays (TMA) in studies that profile TIL burden is attractive but given the potential for intra-tumoural heterogeneity to introduce sampling errors, the adequacy of this approach is undetermined. In this study, we assessed the histological inter- and intra-tumoural heterogeneity in TIL burden within a retrospective cohort of primary LMS specimens. Using a virtual TMA approach, we also analysed the optimal number of TMA cores required to provide an accurate representation of TIL burden in a full tissue section. We establish that LMS have generally low and spatially homogenous TIL burdens, although a small proportion exhibit higher levels and more heterogeneous distribution of TILs. We show that a conventional and practical number (e.g. ≤3) of TMA cores is adequate for correct ordinal categorisation of tumours with high or low TIL burden, but that many more cores (≥11) are required to accurately estimate absolute TIL numbers. Our findings provide a benchmark for the design of future studies aiming to define the clinical relevance of the immune microenvironments of LMS and other sarcoma subtypes.
Frictional Damping from Biomimetic Scales
Authors: Ali Hessein , Ebrahimi Hossein , Ghosh Ranajay
Published: October 2019

Stiff scales adorn the exterior surfaces of fishes, snakes, and many reptiles. They provide protection from external piercing attacks and control over global deformation behavior to aid locomotion, slithering, and swimming across a wide range of environmental condition. In this report, we investigate the dynamic behavior of biomimetic scale substrates for further understanding the origins of the nonlinearity that involve various aspect of scales interaction, sliding kinematics, interfacial friction, and their combination. Particularly, we study the vibrational characteristics through an analytical model and numerical investigations for the case of a simply supported scale covered beam. Our results reveal for the first time that biomimetic scale beams exhibit viscous damping behavior even when only Coulomb friction is postulated for free vibrations. We anticipate and quantify the anisotropy in the damping behavior with respect to curvature. We also find that unlike static pure bending where friction increases bending stiffness, a corresponding increase in natural frequency for the dynamic case does not arise for simply supported beam. Since both scale geometry, distribution and interfacial properties can be easily tailored, our study indicates a biomimetic strategy to design exceptional synthetic materials with tailorable damping behavior.
Interactive spatial scale effects on species distribution modeling: The case of the giant panda
Authors: Connor Thomas , Viña Andrés , Winkler Julie A. , Hull Vanessa , Tang Ying , Shortridge Ashton , Yang Hongbo , Zhao Zhiqiang , Wang Fang , Zhang Jindong , Zhang Zejun , Zhou Caiquan , Bai Wenke , Liu Jianguo
Published: October 2019

Research has shown that varying spatial scale through the selection of the total extent of investigation and the grain size of environmental predictor variables has effects on species distribution model (SDM) results and accuracy, but there has been minimal investigation into the interactive effects of extent and grain. To do this, we used a consistently sampled range-wide dataset of giant panda occurrence across southwest China and modeled their habitat and distribution at 4 extents and 7 grain sizes. We found that increasing grain size reduced model accuracy at the smallest extent, but that increasing extent negated this effect. Increasing extent also generally increased model accuracy, but the models built at the second-largest (mountain range) extent were more accurate than those built at the largest, geographic range-wide extent. When predicting habitat suitability in the smallest nested extents (50 km2), we found that the models built at the next-largest extent (500 km2) were more accurate than the smallest-extent models but that further increases in extent resulted in large decreases in accuracy. Overall, this study highlights the impacts of the selection of spatial scale when evaluating species’ habitat and distributions, and we suggest more explicit investigations of scale effects in future modeling efforts.
The explant developmental stage profoundly impacts small RNA-mediated regulation at the dedifferentiation step of maize somatic embryogenesis
Authors: Juárez-González Vasti T. , López-Ruiz Brenda A. , Baldrich Patricia , Luján-Soto Eduardo , Meyers Blake C. , Dinkova Tzvetanka D.
Published: October 2019

Maize somatic embryogenesis (SE) requires the induction of embryogenic callus and establishment of proliferation before plant regeneration. The molecular mechanisms underlying callus embryogenic potential are not well understood. Here we explored the role of small RNAs (sRNAs) and the accumulation of their target transcripts in maize SE at the dedifferentiation step using VS-535 zygotic embryos collected at distinct developmental stages and displaying contrasting in vitro embryogenic potential and morphology. MicroRNAs (miRNAs), trans-acting siRNAs (tasiRNAs), heterochromatic siRNAs (hc-siRNAs) populations and their RNA targets were analyzed by high-throughput sequencing. Abundances of specific miRNAs, tasiRNAs and targets were validated by qRT-PCR. Unique accumulation patterns were found for immature embryo at 15 Days After Pollination (DAP) and for the callus induction from this explant, as compared to 23 DAP and mature embryos. miR156, miR164, miR166, tasiARFs and the 24 nt hc-siRNAs displayed the most strikingly different patterns between explants and during dedifferentiation. According to their role in auxin responses and developmental cues, we conclude that sRNA-target regulation operating within the 15 DAP immature embryo explant provides key molecular hints as to why this stage is relevant for callus induction with successful proliferation and plant regeneration.
Risk of end-stage renal disease in patients with hypertrophic cardiomyopathy: A nationwide population-based cohort study
Authors: Lee Heesun , Han Kyungdo , Park Jun-Bean , Hwang In-Chang , Yoon Yeonyee E. , Park Hyo Eun , Choi Su-Yeon , Kim Yong-Jin , Cho Goo-Yeong , Kim Hyung-Kwan , Ommen Steve R.
Published: October 2019

Although hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has mortality rate as low as general population, previous studies have focused on identifying high-risk of sudden cardiac death. Thus, long-term systemic impact of HCM is still unclear. We sought to investigate the association between HCM and end-stage renal disease (ESRD). This was a nationwide population-based cohort study using the National Health Insurance Service database. We investigated incident ESRD during follow-up in 10,300 adult patients with HCM (age 62.1 years, male 67.3%) and 51,500 age-, sex-matched controls. During follow-up (median 2.8 years), ESRD developed in 197 subjects; 111 (1.08%) in the HCM, and 86 (0.17%) in the non-HCM (incidence rate 4.14 vs. 0.60 per 1,000 person-years, p < 0.001). In the HCM, the incidence rate for ESRD gradually increased with age, but an initial peak and subsequent plateau in age-specific risk were observed. HCM was a significant predictor for ESRD (unadjusted HR 6.90, 95% CI 5.21–9.15, p < 0.001), as comparable to hypertension and diabetes mellitus. Furthermore, after adjusting for all variables showing the association in univariate analysis, HCM itself remained a robust predictor of ESRD development (adjusted HR 3.93, 95% CI 2.82–5.46, p < 0.001). The consistent associations between HCM and ESRD were shown in almost all subgroups other than smokers and subjects with a history of stroke. Conclusively, HCM increased the risk of ESRD, regardless of known prognosticators. It provides new insight into worsening renal function in HCM, and active surveillance for renal function should be considered.