bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioactive, Ion‐Releasing PMMA Bone Cement Filled with Functional Graphenic Materials
Authors: Wright Zoe M. , Pandit Avanti M. , Karpinsky Michelle M. , Holt Brian D. , Zovinka Edward P. , Sydlik Stefanie A.
Published: December 2020

Graphene oxide and functionalized graphenic materials (FGMs) have promise as platforms for imparting programmable bioactivity to poly(methyl methacrylate) (PMMA)‐based bone cement. To date, however, graphenic fillers have only been feasible in PMMA cements at extremely low loadings, limiting the bioactive effects. At higher loadings, graphenic fillers decrease cement strength by aggregating and interfering with curing process. Here, these challenges are addressed by combining bioactive FGM fillers with a custom cement formulation. These cements contain an order of magnitude more graphenic filler than previous reports. Even at 1 wt% FGM, these cements have compressive strengths of 78– 88 MPa, flexural strengths of 74–81 MPa, and flexural stiffnesses of 1.8–1.9 GPa, surpassing the ASTM requirements for bone cement and competing with traditional PMMA cement. Further, by utilizing designer FGMs with programmed bioactivity, these cements demonstrate controlled release of osteogenic calcium ions (releasing a total of 5 ± 2 µmol of Ca2+ per gram of cement over 28 d) and stimulate a 290% increase in expression of alkaline phosphatase in human mesenchymal stem cells in vitro. Also, design criteria are described to guide creation of future generations of bone cements that utilize FGMs as platforms to achieve dynamic biological activity.
Forecasting exchange rates for Central and Eastern European currencies using country‐specific factors
Authors: Jaworski Krystian
Published: December 2020

This study builds on two strands of the literature regarding exchange rates—developing methods to forecast them and attempting to find a link between exchange rates and macroeconomic fundamentals (i.e., addressing so called “exchange rate disconnect puzzle”). We propose looking separately at its global component (common for all the currencies) and the local component (country‐specific one) instead of modeling and forecasting the exchange rate directly. We demonstrate that in the last few years, local factors have been gaining importance in shaping the exchange rate returns for the Polish Zloty, Hungarian Forint, Czech Koruna, and Romanian Leu. We further show that the main drivers of the local component of exchange rate returns are the future values of the gross domestic product growth rate and consumer price index inflation. Using principal component analysis combined with linear regression, we exploit this tendency for forecasting purposes. Our novel approach yields superior results compared to the random walk in out‐of‐sample forecasting exercise at horizons of 1 month to over a year in the case of Central and Eastern European currencies. The results withstand the sensitivity and robustness analysis.
The effect of catastrophic health expenditure on exit from poverty among the poor in South Korea
Authors: Kim Eunkyoung , Kwon Soonman
Published: December 2020

The study aims to examine the effect of catastrophic health expenditure (CHE) on exit from poverty among the poor at the poverty line of less than 40% of median income level (MIL), analysing data from the Korean Welfare Panel Study 2008–2016 through a discrete time event history analysis. Effects of CHE on poverty exit were different between exit to near‐poverty and exit to non‐poverty. Households facing CHE were less likely to exit from poverty to near‐poverty at the CHE thresholds of 20%–30%; however, effects of CHE were not associated with exiting from poverty to non‐poverty. Considering the majority of types of exit from poverty were exit to near‐poverty (about 70%), this result would raise concerns that occurrences of CHE may pose a big threat to their already limited household budget of the poor. Combined loss of income due to ill health and financial burden due to health care may force the poor to be stuck at poverty. The study was the first exploratory study in South Korea to examine the effect of CHE on exit from poverty. This study is expected to contribute to better understanding of the economic consequences of out‐of‐pocket payments due to health care among the poor over time. Reduction in the incidence of CHE by expanding the benefits coverage of the national health insurance in Korea can be an important step to reduce poverty.
Hydrogels Generated from Cyclic Poly(2‐Oxazoline)s Display Unique Swelling and Mechanical Properties
Authors: Trachsel Lucca , Romio Matteo , Zenobi‐Wong Marcy , Benetti Edmondo M.
Published: December 2020

Cyclic macromolecules do not feature chain ends and are characterized by a higher effective intramolecular repulsion between polymer segments, leading to a higher excluded‐volume effect and greater hydration with respect to their linear counterparts. As a result of these unique properties, hydrogels composed of cross‐linked cyclic polymers feature enhanced mechanical strength while simultaneously incorporating more solvent with respect to networks formed from their linear analogues with identical molar mass and chemical composition. The translation of topology effects by cyclic polymers into the properties of polymer networks provides hydrogels that ideally do not include defects, such as dangling chain ends, and display unprecedented physicochemical characteristics.
Justice in Extreme Cases
Authors: Robinson Darryl
Published: December 2020

In Justice in Extreme Cases, Darryl Robinson argues that the encounter between criminal law theory and international criminal law (ICL) can be illuminating in two directions: criminal law theory can challenge and improve ICL, and conversely, ICL's novel puzzles can challenge and improve mainstream criminal law theory. Robinson recommends a 'coherentist' method for discussions of principles, justice and justification. Coherentism recognizes that prevailing understandings are fallible, contingent human constructs. This book will be a valuable resource to scholars and jurists in ICL, as well as scholars of criminal law theory and legal philosophy.
Emma
Authors: Austen Jane
Published: December 2020

Emma is Austen's most technically accomplished novel, with a hidden plot, the full implications of which are only revealed by a second reading. It is here presented for the first time with a full scholarly apparatus. The text retains the spelling and the punctuation of the first edition of 1816, allowing readers to see the novel as Austen's contemporaries first encountered it. This volume, first published in 2005, provides comprehensive explanatory notes, an extensive critical introduction covering the context and publication history of the work, a chronology of Austen's life and an authoritative textual apparatus.
Context-specific volume–delay curves by combining crowd-sourced traffic data with automated traffic counters: A case study for London
Authors: Casey Gerard , Zhao Bingyu , Kumar Krishna , Soga Kenichi
Published: December 2020

Traffic congestion across the world has reached chronic levels. Despite many technological disruptions, one of the most fundamental and widely used functions within traffic modeling, the volume–delay function has seen little in the way of change since it was developed in the 1960s. Traditionally macroscopic methods have been employed to relate traffic volume to vehicular journey time. The general nature of these functions enables their ease of use and gives widespread applicability. However, they lack the ability to consider individual road characteristics (i.e., geometry, presence of traffic furniture, road quality, and surrounding environment). This research investigates the feasibility to reconstruct the model using two different data sources, namely the traffic speed from Google Maps’ Directions Application Programming Interface (API) and traffic volume data from automated traffic counters (ATC). Google’s traffic speed data are crowd-sourced from the smartphone Global Positioning System (GPS) of road users, able to reflect real-time, context-specific traffic condition of a road. On the other hand, the ATCs enable the harvesting of the vehicle volume data over equally fine temporal resolutions (hourly or less). By combining them for different road types in London, new context-specific volume–delay functions can be generated. This method shows promise in selected locations with the generation of robust functions. In other locations, it highlights the need to better understand other influencing factors, such as the presence of on-road parking or weather events.
Anti-hyperglycaemic and insulin-releasing effects of Camellia sinensis leaves and isolation and characterisation of active compounds
Authors: Ansari Prawej , Flatt Peter R. , Harriott Patrick , Abdel-Wahab Yasser H. A.
Published: December 2020

Anti-diabetic actions of Camellia sinensis leaves, used traditionally for type 2 diabetes (T2DM) treatment, have been determined. Insulin release, membrane potential and intra-cellular Ca were studied using the pancreatic β-cell line, BRIN-BD11 and primary mouse pancreatic islets. Cellular glucose-uptake/insulin action by 3T3-L1 adipocytes, starch digestion, glucose diffusion, dipeptidyl peptidase-4 (DPP-IV) activity and glycation were determined together with in vivo studies assessing glucose homoeostasis in high-fat-fed (HFF) rats. Active phytoconstituents with insulinotropic activity were isolated using reversed-phase HPLC, LCMS and NMR. A hot water extract of C. sinensis increased insulin secretion in a concentration-dependent manner. Insulinotropic effects were significantly reduced by diazoxide, verapamil and under Ca-free conditions, being associated with membrane depolarisation and increased intra-cellular Ca2+. Insulin-releasing effects were observed in the presence of KCl, tolbutamide and isobutylmethylxanthine, indicating actions beyond K+ and Ca2+ channels. The extract also increased glucose uptake/insulin action in 3T3L1 adipocyte cells and inhibited protein glycation, DPP-IV enzyme activity, starch digestion and glucose diffusion. Oral administration of the extract enhanced glucose tolerance and insulin release in HFF rats. Extended treatment (250 mg/5 ml per kg orally) for 9 d led to improvements of body weight, energy intake, plasma and pancreatic insulin, and corrections of both islet size and β-cell mass. These effects were accompanied by lower glycaemia and significant reduction of plasma DPP-IV activity. Compounds isolated by HPLC/LCMS, isoquercitrin and rutin (464·2 Da and 610·3 Da), stimulated insulin release and improved glucose tolerance. These data indicate that C. sinensis leaves warrant further evaluation as an effective adjunctive therapy for T2DM and source of bioactive compounds.
Socioeconomic deprivation in early life and symptoms of depression and anxiety in young adulthood: mediating role of hippocampal connectivity
Authors: Čermaková Pavla , Andrýsková Lenka , Brázdil Milan , Marečková Klára
Published: December 2020

Background

Experience of early-life socioeconomic deprivation (ELSD) may increase the risk of mental disorders in young adulthood. This association may be mediated by structural and functional alterations of the hippocampus.

Methods

We conducted a prospective cohort study on 122 participants of the European Longitudinal Study of Pregnancy and Childhood. Information about ELSD was collected via questionnaire from mothers during the first 18 months of participants’ lives. At age 23–24, participants underwent examination by structural magnetic resonance imaging, resting-state functional connectivity and assessment of depressive symptoms (Mood and Feelings Questionnaire) and anxiety (Spielberger State-Trait Anxiety Inventory). The association of ELSD with brain outcomes in young adulthood was assessed with correlations, linear regression (adjusting for sex, socioeconomic position and mother's mental health) and moderated mediation analysis.

Results

Higher ELSD was associated with greater depressive symptoms (B = 0.22; p = 0.001), trait anxiety (B = 0.07; p = 0.02) and lower global connectivity of the right hippocampus (B = −0.01; p = 0.02). These associations persisted when adjusted for covariates. In women, lower global connectivity of the right hippocampus was associated with stronger trait anxiety (B = −4.14; p = 0.01). Global connectivity of the right hippocampus as well as connectivity between the right hippocampus and the left middle temporal gyrus mediated the association between ELSD and trait anxiety in women. Higher ELSD correlated with a lower volume of the right hippocampus in men, but the volume of the right hippocampus was not related to mental health.

Conclusions

Early preventive strategies targeted at children from socioeconomically deprived families may yield long-lasting benefits for the mental health of the population.
THE EAR IS A LABYRINTH: JULIO ESTRADA SEARCHING FOR THE MINOTAUR
Authors: Chin Pablo Santiago
Published: December 2020

This article explores Julio Estrada's musical thinking in his early and recent works. Estrada's early works precede the development of his graphication method in the 1980s, and his recent works follow the completion of his opera Murmullos del Páramo in 2006. It is his music of these three decades between 1980 and 2006 that is most widely scrutinised – a music centred on the extensive conception and manifestation of sound as a continuum and aided in the creational process by coloured drawings on graph paper – but this article focuses on lesser-known pieces from the 1970s like Melódica and Solo para uno, as well as recent works such as his opera-in-progress, a major project conceived as a book to be read and imagined, rather than performed. It is hoped that close examination of these pieces will significantly broaden the understanding of Estrada's creative drive and lifelong research, revealing how these works entangle with his better-known developments of the sound continuum and graphication method and share common concerns with work from across his career.
Hamilcar of Barce? Discerning Barcid proto-history and Polybius’ mixellēnes
Authors: Hill Andrew M.
Published: December 2020

Hamilcar and Hannibal Barca embody a colossal father-son military legacy. Yet their family – the so-called ‘Barcid’ dynasty – has a murky history. Modern scholars have presumed that Hamilcar, the first notable historical figure to bear the name Barkas, received it as a ‘nickname’ meaning ‘lightning’. The rationale is that the name derives from the Phoenician word brq and is thus the equivalent to the Greek epithet Keraunos. There is, however, no evidence in our classical sources, to which exclusively we owe our knowledge of events, supporting this. Furthermore, the name Barca was passed on to Hamilcar’s sons, something suggestive of an inherited family surname. This article submits an alternative to the widely endorsed ‘lightning’ theory. This new perspective explores the possibility that the Barcid dynasty had roots in the city of Barce in Cyrenaica and was a relatively new addition to the Carthaginian aristocracy in the third century BC. Using textual evidence from Polybius, Diodorus and others, this fresh take clarifies other aspects of the Barcid dynasty’s tumultuous history, such as their animosity towards the Carthaginian Council of Elders and their departure to Spain in the 220s.
The historian Philip of Pergamon
Authors: Jones Christopher P.
Published: December 2020

This article studies the inscription IG IV2 1.687 (FGrH 95), the only evidence for the historian Philip of Pergamon. The subjects considered include the text itself, the appearance of the stone and the layout in imitation of papyrus, the date as evidenced by the lettering, the use of the Ionic dialect and the references to ‘suffering and continuous mutual slaughter’. Finally, it is proposed that Philip may be ‘the historian Philip’ mentioned in a dialogue of Plutarch.
Ventricular septal defect: diagnosis and treatments in the neonates: a systematic review
Authors: Adan Ahmed , Eleyan Loay , Zaidi Mariam , Ashry Amr , Dhannapuneni Ram , Harky Amer
Published: December 2020

Background:

Medical advancements have encouraged minimally invasive surgical repair of congenital heart defects such as ventricular septal defects (VSDs), and the diagnostic process can now be carried out using non-traditional techniques such as pulse oximetry. This, in turn, has improved clinical outcomes with reduced complication rates post-surgery. However, the variations in type of VSDs, age of patient, comorbidities, and access to closure devices may limit the efficacy of surgical advancements.

Methods:

Articles were identified amongst Scopus, MEDLINE, and PubMed using various relevant search strings using PRISMA guidelines. Of the 115 articles initially extracted, 10 were eventually reviewed after duplicates and irrelevant studies were removed.

Results:

Of the 24 eligible articles, 10 papers were selected for analysis. Minimally invasive approaches to VSD repair was associated with satisfactory short-term outcomes when compared to open repair. For diagnosis of congenital VSD, whilst recent advances such as pulse oximetry method and genome analysis are more sensitive, the limited availability and access to such investigatory methods must be recognised.

Conclusion:

Pulse oximetry and fetal echocardiography are established non-invasive diagnostic tools for VSD. The recent advances in minimally invasive treatment options including periventricular approach and transcatheter techniques have improved patient outcomes, yet at the expense of higher residual rates. Careful patient selection for each technique and follow-up should be planned through multidisciplinary team meetings.
Sexual orientation and food insecurity: findings from the New York City Community Health Survey
Authors: Testa Alexander , Jackson Dylan B
Published: December 2020

Objective:

Food insecurity is a serious public health concern that disproportionately impacts minority groups. However, limited research has assessed food insecurity among sexual minorities. The current study investigates whether individuals identifying as lesbian/gay or bisexual (LGB) sexual orientation were more likely to experience food insecurity relative to heterosexual persons.

Design:

Data are from the 2017 and 2018 New York City Community Health Survey. Multinomial logistic regression is used to assess the association between sexual orientation and food insecurity.

Setting:

A sample of adults (18 years and older) who identify as heterosexual, gay/lesbian or bisexual living in New York City in 2017 and 2018.

Participants:

18 610 non-institutionalised adults.

Results:

Bisexual individuals have significantly higher rates of both mild (relative risk ratio (RRR) = 1·719, 95 % CI 1·148, 2·573) and moderate-to-severe food insecurity (RRR = 1·851, 95 % CI 1·097, 3·122) relative to heterosexual individuals, net of covariates from demographic, household and socio-economic characteristics. Study findings showed no difference in the likelihood of food insecurity between gay/lesbian individuals and heterosexual individuals.

Conclusion:

Results illustrate a complex interplay between sexual orientation and food insecurity among adults living in New York City. Findings suggest that efforts to connect LGB individuals to public assistance programmes such as Supplemental Nutritional Assistance Program, as well as providing information and connections to food assistance through local LGBTQ+ centres, government agencies (i.e., NYC Human Resources Administration) and non-profit organisations (i.e., Food Bank for New York City) may be beneficial approaches to alleviate food insecurity among this population.
Religious Elite Cues, Internal Division, and the Impact of Pope Francis' Laudato Si'
Authors: Buckley David T.
Published: December 2020

What impact do cues from religious elites have on followers, particularly when religious communities are internally divided? Could religious elites promote internal consensus, or would their cues stoke further internal polarization? This article utilizes the release of Pope Francis's encyclical on the environment, Laudato Si', to explore these questions. A unique survey experiment, conducted on a nationally representative sample of Catholic voters in the United States in late 2015, tests the impact of Francis' message relative to a similar message from unidentified environmental elites. In keeping with other studies of Laudato's impact in the United States, findings reveal real, but nuanced, effects from Francis' environmental cue. The Francis cue did impact conservatives and high religiosity Catholics, but these effects were not distinct from those on other Catholics in the sample, suggesting limitations in promoting consensus. Instead, responses to a Francis cue varied sharply depending on pre-existing views of Francis' leadership.
Space Weather as the Nexus of Applied and Fundamental Space Science: The Need for Separate Funding Mechanisms and Definition
Authors:   Space Weather Editors
Published: December 2020

This editorial aims at highlighting the importance of keeping space science and space weather fundamental and applied research highly interconnected, but also separate through distinct funding mechanisms. Fundamental and applied space research endeavors are not the same, even though they may share some of the same science regions and approaches, and scientists.
Coinfection and infection duration shape how pathogens affect the African buffalo gut microbiota
Authors: Sabey Kate A , Song Se Jin , Jolles Anna , Knight Rob , Ezenwa Vanessa O
Published: December 2020

Changes in the gut microbiota during pathogen infection are often predicted to influence disease outcomes. However, studies exploring whether pathogens induce microbiota shifts have yielded inconsistent results. This suggests that variation in infection, rather than the presence of infection alone, might shape pathogen–microbiota relationships. For example, most hosts are coinfected with multiple pathogens simultaneously, and hosts vary in how long they are infected, which may amplify or diminish microbial shifts expected in response to a focal pathogen. We used a longitudinal anthelmintic treatment study of free-ranging African buffalo (Syncerus caffer) to examine whether (i) coinfection with bovine tuberculosis (Mycobacterium bovis, TB) and gastrointestinal nematodes, and (ii) the duration of TB infection, modified effects of single pathogens on the gut microbiota. By accounting for the interaction between TB and nematodes, we found that coinfection affected changes in microbial abundance associated with single infections. Furthermore, the duration of TB infection predicted more microbiota variation than the presence of TB. Importantly, coinfection and infection duration had nearly as much influence on microbial patterns as demographic and environmental factors commonly examined in microbiota research. These findings demonstrate that acknowledging infection heterogeneities may be crucial to understanding relationships between pathogens and the gut microbiota.
Systems biology drug screening identifies statins as enhancers of current therapies in chronic lymphocytic leukemia
Authors: Gimenez Neus , Tripathi Rupal , Giró Ariadna , Rosich Laia , López-Guerra Mònica , López-Oreja Irene , Playa-Albinyana Heribert , Arenas Fabian , Mas José Manuel , Pérez-Galán Patricia , Delgado Julio , Campo Elias , Farrés Judith , Colomer Dolors
Published: December 2020

Chronic lymphocytic leukemia (CLL) is a B lymphoid malignancy highly dependent on the microenvironment. Despite new targeted therapies such as ibrutinib and venetoclax, disease progression and relapse remain an issue. CLL cell interactions with the supportive tissue microenvironment play a critical role in disease pathogenesis. We used a platform for drug discovery based on systems biology and artificial intelligence, to identify drugs targeting key proteins described to have a role in the microenvironment. The selected compounds were screened in CLL cell lines in the presence of stromal cells to mimic the microenvironment and validated the best candidates in primary CLL cells. Our results showed that the commercial drug simvastatin was the most effective and selective out of the tested compounds. Simvastatin decreased CLL cell survival and proliferation as well as cell adhesion. Importantly, this drug enhanced the antitumor effect of venetoclax and ibrutinib. We proposed that systems biology approaches combined with pharmacological screening could help to find new drugs for CLL treatment and to predict new combinations with current therapies. Our results highlight the possibility of repurposing widely used drugs such as statins to target the microenvironment and to improve the efficacy of ibrutinib or venetoclax in CLL cells.
Detecting methylation signatures in neurodegenerative disease by density-based clustering of applications with reducing noise
Authors: Mallik Saurav , Zhao Zhongming
Published: December 2020

There have been numerous genetic and epigenetic datasets generated for the study of complex disease including neurodegenerative disease. However, analysis of such data often suffers from detecting the outliers of the samples, which subsequently affects the extraction of the true biological signals involved in the disease. To address this critical issue, we developed a novel framework for identifying methylation signatures using consecutive adaptation of a well-known outlier detection algorithm, density based clustering of applications with reducing noise (DBSCAN) followed by hierarchical clustering. We applied the framework to two representative neurodegenerative diseases, Alzheimer’s disease (AD) and Down syndrome (DS), using DNA methylation datasets from public sources (Gene Expression Omnibus, GEO accession ID: GSE74486). We first applied DBSCAN algorithm to eliminate outliers, and then used Limma statistical method to determine differentially methylated genes. Next, hierarchical clustering technique was applied to detect gene modules. Our analysis identified a methylation signature comprising 21 genes for AD and a methylation signature comprising 89 genes for DS, respectively. Our evaluation indicated that these two signatures could lead to high classification accuracy values (92% and 70%) for these two diseases. In summary, this framework will be useful to better detect outlier-free genetic and epigenetic signatures in various complex diseases and their developmental stages.
Cell non-autonomous requirement of p75 in the development of geniculate oral sensory neurons
Authors: Tang Tao , Donnelly Christopher R. , Shah Amol A. , Bradley Robert M. , Mistretta Charlotte M. , Pierchala Brian A.
Published: December 2020

During development of the peripheral taste system, oral sensory neurons of the geniculate ganglion project via the chorda tympani nerve to innervate taste buds in fungiform papillae. Germline deletion of the p75 neurotrophin receptor causes dramatic axon guidance and branching deficits, leading to a loss of geniculate neurons. To determine whether the developmental functions of p75 in geniculate neurons are cell autonomous, we deleted p75 specifically in Phox2b + oral sensory neurons (Phox2b-Cre; p75fx/fx) or in neural crest-derived cells (P0-Cre; p75fx/fx) and examined geniculate neuron development. In germline p75−/− mice half of all geniculate neurons were lost. The proportion of Phox2b + neurons, as compared to Phox2b-pinna-projecting neurons, was not altered, indicating that both populations were affected similarly. Chorda tympani nerve recordings demonstrated that p75−/− mice exhibit profound deficits in responses to taste and tactile stimuli. In contrast to p75−/− mice, there was no loss of geniculate neurons in either Phox2b-Cre; p75fx/fx or P0-Cre; p75fx/fx mice. Electrophysiological analyses demonstrated that Phox2b-Cre; p75fx/fx mice had normal taste and oral tactile responses. There was a modest but significant loss of fungiform taste buds in Phox2b-Cre; p75fx/fx mice, although there was not a loss of chemosensory innervation of the remaining fungiform taste buds. Overall, these data suggest that the developmental functions of p75 are largely cell non-autonomous and require p75 expression in other cell types of the chorda tympani circuit.
Epidemiology of a SKin Ulceration Disease (SKUD) in the sea cucumber Holothuria scabra with a review on the SKUDs in Holothuroidea (Echinodermata)
Authors: Delroisse Jérôme , Van Wayneberghe Kévin , Flammang Patrick , Gillan David , Gerbaux Pascal , Opina Noel , Todinanahary Gildas Georges Boleslas , Eeckhaut Igor
Published: December 2020

Aquacultivated sea cucumbers often suffer from SKin Ulceration Diseases (SKUDs). SKUDs have been observed in six holothuroid species from nine countries. All SKUDs present a similar symptom—the skin ulceration—and can be induced by bacteria, viruses, or abiotic factors. We here provide an update on SKUDs in holothuroids and analyse the case of the SKUD observed in Holothuria scabra in Madagascar. Field observations revealed a seasonality of the disease (i.e. wintertime maximum peak). Morphological analyses of integument ulcers showed that sea cucumbers react by forming a collagen fibre plug. Metagenomic analyses revealed a higher proportion of Vibrionaceae (Gammaproteobacteria) in ulcers in comparison to the healthy integument of the same individuals. Experimental infection assays were performed with ulcer crude extracts and bacteria isolated from these extracts (e.g. Vibrio parahaemolyticus) but did not significantly induce skin ulceration. Our results suggest that the disease is not induced by a pathogen or, at the very least, that the pathogen is not found within the ulcers as the disease is not transmissible by contact. An initial cause of the SKUD in Madagascar might be the repeated and prolonged exposures to cold temperatures. Opportunistic bacteria could settle in the dermis of ulcerated individuals and promote the ulcer extension. We propose a general nomenclature for SKUDs based on the acronym of the disease, the affected sea cucumber species (e.g. Hs for Holothuria scabra), the concerned region using an ISO code 3166-2 (e.g. MG for Madagascar), the description date (e.g. 20 for the year 2020), and, when known, the inducing agent (first letter of the general taxon, b for bacteria, v for virus in currently known cases; a a if it is an abiotic inducing parameter; nothing if the inducing cause has not been precisely identified). The disease described in this work will be designated under the name SKUD Hs-MG-20.
Frequency-diverse multimode millimetre-wave constant-ϵr lens-loaded cavity
Authors: Abbasi M. A. B. , Fusco V. F. , Yurduseven O. , Fromenteze T.
Published: December 2020

This paper presents a physical frequency-diverse multimode lens-loaded cavity, designed and used for the purpose of the direction of arrival (DoA) estimation in millimetre-wave frequency bands for 5G and beyond. The multi-mode mechanism is realized using an electrically-large cavity, generating spatio-temporally incoherent radiation masks leveraging the frequency-diversity principle. It has been shown for the first time that by placing a spherical constant dielectric lens (constant-ϵr) in front of the radiating aperture of the cavity, the spatial incoherence of the radiation modes can be enhanced. The lens-loaded cavity requires only a single lens and output port, making the hardware development much simpler and cost-effective compared to conventional DoA estimators where multiple antennas and receivers are classically required. Using the lens-loaded architecture, an increase of up to 6 dB is achieved in the peak gain of the synthesized quasi-random sampling bases from the frequency-diverse cavity. Despite the fact that the practical frequency-diverse cavity uses a limited subset of quasi-orthogonal modes below the upper bound limit of the number of theoretical modes, it is shown that the proposed lens-loaded cavity is capable of accurate DoA estimation. This is achieved thanks to the sufficient orthogonality of the leveraged modes and to the presence of the spherical constant-ϵr lens which increases the signal-to-noise ratio (SNR) of the received signal. Experimental results are shown to verify the proposed approach.
Antler cannibalism in reindeer
Authors: Mysterud Atle , Ytrehus Bjørnar , Tranulis Michael A. , Rauset Geir Rune , Rolandsen Christer M. , Strand Olav
Published: December 2020

Prion diseases constitute a class of invariably fatal and degenerative encephalopathies. Chronic Wasting Disease (CWD) is a contagious prion disease among cervids, which is spreading and causing marked population declines in USA and Canada. The first outbreak of CWD in Europe was discovered in a reindeer population in Norway in 2016. In the worst-case scenario with continental-wide spreading of CWD in Eurasia, an annual harvest of around 4 million cervids is at stake only in Europe, with huge economic and cultural significance. An in situ origin of CWD was suspected, and it appear urgent to identify the likely cause to prevent future emergences. Here, we document the novel phenomenon of extensive antler cannibalism prior to shedding among reindeer in the CWD-infected population. The extent of antler cannibalism increased over the last decades when CWD emerged, and included ingestion of vascularized antlers. Ingestion of tissues from conspecifics is a risk factor for the emergence of prion diseases, where the presence of extensive antler cannibalism opens the intriguing possibility of a ‘Kuru-analogue’ origin of CWD among the reindeer in Europe. Based on general insight on pathology of prion diseases and strain selection processes, we propose an hypothesis for how contagious CWD may emerge from sporadic CWD under the unique epidemiological conditions we document here. More research is required to document the presence of prions in reindeer antlers, and whether antler cannibalism actually led to a strain selection process and the emergence of a contagious form of CWD from a sporadic form of CWD.
Differential diagnosis of vergence and saccade disorders in dyslexia
Authors: Ward Lindsey M. , Kapoula Zoï
Published: December 2020

Previous studies suggest vergence and saccade abnormalities in dyslexic adolescents. However, these studies are mainly clinically based and do not provide objective measurements of eye movements, but rather subjectively evaluate vergence using haplosopic conditions in which the two eyes are dissociated (via polarizers, prisms, or intermittent spectacles). Other studies have identified deficits with binocular coordination during reading in dyslexics. Yet, there are few studies that provide objective measurements of eye movements in the dyslexic population to help provide more information regarding if these deficits could be due to an intrinsic motor problem or if they are the consequence of poor reading. 47 dyslexic adolescents (18 female, 29 male; mean age 15.5) and 44 non-dyslexic adolescents (22 female, 22 male; mean age 14.8) wore a head-based eye tracker (PupilCore, Pupil Labs, Berlin) which recorded wide angle saccade and vergence eye movements at 200 Hz. Tests were run using the REMOBI device, which produced a saccade or vergence audiovisual target. Analysis of eye movements was performed with lab-developed software, AIDEAL. The results showed statistically significant abnormalities in vergence and saccades. In vergence, dyslexics displayed a reduced amplitude of the visually driven portion of convergence and a longer duration in the initial phase of divergence. In saccades, dyslexic adolescents demonstrated slower saccades in both directions. They also had an increased disconjugate drift in the first 80 or 160 ms following saccades to the right, suggesting poor binocular coordination. For both vergence and saccades, the peak velocity and time to peak velocity was higher and earlier, respectively, in non-dyslexics compared to dyslexics; yet the average velocity of both movements was lower in dyslexics. Thus, these results indicate peculiar velocity profiles in dyslexics, particularly a slow deceleration phase in both vergence and saccades. The study provides an objective method to diagnose vergence and saccade abnormalities while viewing targets in the real three-dimensional space in a dyslexic population. Vergence abnormalities are demonstrated to be a problem in dyslexics, occurring independently from reading. We hypothesize these disconjugate drifts following saccades are the result of slow vergence capacity. Rehabilitation programs, such as those using REMOBI, should aim to target these deficits in vergence velocity, as this has been shown to improve binocular control.
COVID-19 cycles and rapidly evaluating lockdown strategies using spectral analysis
Authors: Nason Guy P.
Published: December 2020

Spectral analysis characterises oscillatory time series behaviours such as cycles, but accurate estimation requires reasonable numbers of observations. At the time of writing, COVID-19 time series for many countries are short: pre- and post-lockdown series are shorter still. Accurate estimation of potentially interesting cycles seems beyond reach with such short series. We solve the problem of obtaining accurate estimates from short series by using recent Bayesian spectral fusion methods. We show that transformed daily COVID-19 cases for many countries generally contain three cycles operating at wavelengths of around 2.7, 4.1 and 6.7 days (weekly) and that shorter wavelength cycles are suppressed after lockdown. The pre- and post-lockdown differences suggest that the weekly effect is at least partly due to non-epidemic factors. Unconstrained, new cases grow exponentially, but the internal cyclic structure causes periodic declines. This suggests that lockdown success might only be indicated by four or more daily falls. Spectral learning for epidemic time series contributes to the understanding of the epidemic process and can help evaluate interventions. Spectral fusion is a general technique that can fuse spectra recorded at different sampling rates, which can be applied to a wide range of time series from many disciplines.
A novel framework for spatio-temporal prediction of environmental data using deep learning
Authors: Amato Federico , Guignard Fabian , Robert Sylvain , Kanevski Mikhail
Published: December 2020

As the role played by statistical and computational sciences in climate and environmental modelling and prediction becomes more important, Machine Learning researchers are becoming more aware of the relevance of their work to help tackle the climate crisis. Indeed, being universal nonlinear function approximation tools, Machine Learning algorithms are efficient in analysing and modelling spatially and temporally variable environmental data. While Deep Learning models have proved to be able to capture spatial, temporal, and spatio-temporal dependencies through their automatic feature representation learning, the problem of the interpolation of continuous spatio-temporal fields measured on a set of irregular points in space is still under-investigated. To fill this gap, we introduce here a framework for spatio-temporal prediction of climate and environmental data using deep learning. Specifically, we show how spatio-temporal processes can be decomposed in terms of a sum of products of temporally referenced basis functions, and of stochastic spatial coefficients which can be spatially modelled and mapped on a regular grid, allowing the reconstruction of the complete spatio-temporal signal. Applications on two case studies based on simulated and real-world data will show the effectiveness of the proposed framework in modelling coherent spatio-temporal fields.
Comparison of computational chemistry methods for the discovery of quinone-based electroactive compounds for energy storage
Authors: Zhang Qi , Khetan Abhishek , Er Süleyman
Published: December 2020

High-throughput computational screening (HTCS) is a powerful approach for the rational and time-efficient design of electroactive compounds. The effectiveness of HTCS is dependent on accuracy and speed at which the performance descriptors can be estimated for possibly millions of candidate compounds. Here, a systematic evaluation of computational methods, including force field (FF), semi-empirical quantum mechanics (SEQM), density functional based tight binding (DFTB), and density functional theory (DFT), is performed on the basis of their accuracy in predicting the redox potentials of redox-active organic compounds. Geometry optimizations at low-level theories followed by single point energy (SPE) DFT calculations that include an implicit solvation model are found to offer equipollent accuracy as the high-level DFT methods, albeit at significantly lower computational costs. Effects of implicit solvation on molecular geometries and SPEs, and their overall effects on the prediction accuracy of redox potentials are analyzed in view of computational cost versus prediction accuracy, which outlines the best choice of methods corresponding to a desired level of accuracy. The modular computational approach is applicable for accelerating the virtual studies on functional quinones and the respective discovery of candidate compounds for energy storage.
Time-resolved RIXS experiment with pulse-by-pulse parallel readout data collection using X-ray free electron laser
Authors: Lu H. , Gauthier A. , Hepting M. , Tremsin A. S. , Reid A. H. , Kirchmann P. S. , Shen Z. X. , Devereaux T. P. , Shao Y. C. , Feng X. , Coslovich G. , Hussain Z. , Dakovski G. L. , Chuang Y. D. , Lee W. S.
Published: December 2020

Time-resolved resonant inelastic X-ray scattering (RIXS) is one of the developing techniques enabled by the advent of X-ray free electron laser (FEL). It is important to evaluate how the FEL jitter, which is inherent in the self-amplified spontaneous emission process, influences the RIXS measurement. Here, we use a microchannel plate (MCP) based Timepix soft X-ray detector to conduct a time-resolved RIXS measurement at the Ti L3-edge on a charge-density-wave material TiSe2. The fast parallel Timepix readout and single photon sensitivity enable pulse-by-pulse data acquisition and analysis. Due to the FEL jitter, low detection efficiency of spectrometer, and low quantum yield of RIXS process, we find that less than 2% of the X-ray FEL pulses produce signals, preventing acquiring sufficient data statistics while maintaining temporal and energy resolution in this measurement. These limitations can be mitigated by using future X-ray FELs with high repetition rates, approaching MHz such as the European XFEL in Germany and LCLS-II in the USA, as well as by utilizing advanced detectors, such as the prototype used in this study.
Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats
Authors: Nishi Hiroki , Yamanaka Daisuke , Masuda Masato , Goda Yuki , Ito Koichi , Hakuno Fumihiko , Takahashi Shin-Ichiro
Published: December 2020

Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats. Here, we first showed that culturing hepatocytes in the medium mimicking the serum amino acid profile of low-arginine diet-fed rats induced TAG accumulation in the cells, indicating that the specific amino acid profile caused TAG accumulation in hepatocytes. Dietary adenine supplementation completely recovered hepatic TAG secretion and abolished hepatic TAG accumulation in rats. A comprehensive non-linear analysis revealed that inhibition of hepatic TAG accumulation by dietary adenine supplementation could be predicted using only serum amino acid concentration data. Comparison of serum amino acid concentrations indicated that histidine, methionine, and branched-chain amino acid (BCAA) concentrations were altered by adenine supplementation. Furthermore, when the serum amino acid profiles of low-arginine diet-fed rats were altered by modifying methionine or BCAA concentrations in their diets, their hepatic TAG accumulation was abolished. Altogether, these results suggest that an increase in methionine and BCAA levels in the serum in response to dietary arginine deficiency is a key causative factor for hepatic TAG accumulation, and dietary adenine supplementation could disrupt this phenomenon by altering serum amino acid profiles.
Single-walled carbon nanotubes as a photo-thermo-acoustic cancer theranostic agent: theory and proof of the concept experiment
Authors: Golubewa L. , Timoshchenko I. , Romanov O. , Karpicz R. , Kulahava T. , Rutkauskas D. , Shuba M. , Dementjev A. , Svirko Yu. , Kuzhir P.
Published: December 2020

Theranostics is the emerging field of medicine that uniquely combines diagnostic techniques and active agents to diagnose and treat medical conditions simultaneously or sequentially. Finding a theranostic agent capable to cure the affected cells and being safe for the healthy ones is the key for successful treatment. Here, we demonstrate that agglomerated single-walled carbon nanotubes (SWCNTs) are promising theranostic agent that enables photo-activated ‘cold’ destruction of the cancer cells keeping their environment alive. The absorption of picosecond pulses by SWCNT agglomerates results in the mechanical (due to photoacoustic effect) rather than photothermal cancer cell destruction, which was visualized by micro-Raman and ultrafast near-infrared CARS. The developed theoretical model allows us to distinguish photothermal, photoacoustic, and photothermoacoustic regimes of the cancer cell destruction, and also to optimize SWCNT-based theranostics recipe.
The novel rexinoid MSU-42011 is effective for the treatment of preclinical Kras-driven lung cancer
Authors: Moerland Jessica A. , Zhang Di , Reich Lyndsey A. , Carapellucci Sarah , Lockwood Beth , Leal Ana S. , Krieger-Burke Teresa , Aleiwi Bilal , Ellsworth Edmund , Liby Karen T.
Published: December 2020

Effective drugs are needed for lung cancer, as this disease remains the leading cause of cancer-related deaths. Rexinoids are promising drug candidates for cancer therapy because of their ability to modulate genes involved in inflammation, cell proliferation or differentiation, and apoptosis through activation of the retinoid X receptor (RXR). The only currently FDA-approved rexinoid, bexarotene, is ineffective as a single agent for treating epithelial cancers and induces hypertriglyceridemia. Here, we used a previously validated screening paradigm to evaluate 23 novel rexinoids for biomarkers related to efficacy and safety. These biomarkers include suppression of inducible nitric oxide synthase (iNOS) and induction of sterol regulatory element-binding protein (SREBP). Because of its potent iNOS suppression, low SREBP induction, and activation of RXR, MSU-42011 was selected as our lead compound. We next used MSU-42011 to treat established tumors in a clinically relevant Kras-driven mouse model of lung cancer. KRAS is one of the most common driver mutations in human lung cancer and correlates with aggressive disease progression and poor patient prognosis. Ultrasound imaging was used to detect and monitor tumor development and growth over time in the lungs of the A/J mice. MSU-42011 markedly decreased the tumor number, size, and histopathology of lung tumors compared to the control and bexarotene groups. Histological sections of lung tumors in mice treated with MSU-42011 exhibited reduced cell density and fewer actively proliferating cells compared to the control and bexarotene-treated tumors. Although bexarotene significantly (p < 0.01) elevated plasma triglycerides and cholesterol, treatment with MSU-42011 did not increase these biomarkers, demonstrating a more favorable toxicity profile in vivo. The combination of MSU-42011 and carboplatin and paclitaxel reduced macrophages in the lung and increased activation markers of CD8+T cells compared to the control groups. Our results validate our screening paradigm for in vitro testing of novel rexinoids and demonstrate the potential for MSU-42011 to be developed for the treatment of KRAS-driven lung cancer.