bluuebunny/crossref_metadata_2025 huggingface dataset:
JUSTIFYING BLASPHEMY LAWS: FREEDOM OF EXPRESSION, PUBLIC MORALS, AND INTERNATIONAL HUMAN RIGHTS LAW
Authors: Cox Neville
Published: May 2020

In its General Comment No. 34 dealing with freedom of expression, the United Nations Human Rights Committee (UNHRC) rejected the idea that a blasphemy law could ever be human-rights compliant, unless its function was to prevent incitement to religious or racial hatred. This is a widely shared view that is consistently endorsed when any international blasphemy controversy (such as that involving the Danish Cartoons in 2005) arises. This article assesses the legitimacy of this view. The International Covenant on Civil and Political Rights (ICCPR) permits freedom of expression to be limited inter alia in the name of public morality, provided that the law in question is also necessary to achieve this end. This article argues that because a blasphemy law can be a response to a public moral vision; therefore a blasphemy law can serve a legitimate purpose insofar as human rights law is concerned. It is further submitted that whereas some blasphemy laws are unacceptably draconian, it is not inherently impossible for such a law to represent a proportionate response to a public morals concern. Thus, the conclusion from the UNHRC is not warranted by the text of the ICCPR. Moreover, there is a risk that, in reaching this conclusion the committee is evincing an exclusively secularist worldview in its interpretation of the ICCPR that undermines its claim to universality.
THE LEGAL NOTION OF “TRADITIONAL” RELIGIONS IN LITHUANIA AND ITS SOCIOPOLITICAL CONSEQUENCES
Authors: Račius Egdūnas
Published: May 2020

Lithuania formally distinguishes between what it terms “traditional,” “state-recognized,” “registered,” and “unregistered” religions. Though constitutionally Lithuania is a secular state and all religions are declared equal vis-à-vis the state, religious communities recognized as “traditional” have, nonetheless, been favored by the state. They have been granted preferential treatment both in the legislation and extralegal handling by various state actors and institutions. At the same time, traditional religious communities are formally equal among themselves and vis-à-vis the state. However, the size of their membership puts them into two distinct camps. While the Catholic community constitutes 77 percent of the country's population, the remaining eight traditional religious communities together hardly make up 6 percent, of which 4 percent are Orthodox, with Lutherans, Calvinists, Greek Catholics, Old Believers, Judaists, Karaites, and Sunni Muslims making up the remaining numbers. This article focuses on one of the smaller traditional religious communities, Sunni Muslims, and through this example seeks to show looming complications arising from the current legal system for the governance of religion in Lithuania, which, as a country, starts inter alia being affected by the appearance of revivalist and other “nontraditional” forms of Islam on its territory. The article argues that with the changing makeup of the Lithuanian religious landscape—not related only to Islam—the current system of the governance of religion is not only outdated but also unsustainable and needs to be thoroughly overhauled to come more in line with the developing social reality.
Dietary supplementation withLactobacillus plantarummodified gut microbiota, bile acid profile and glucose homoeostasis in weaning piglets
Authors: Lin Sen , Yang Xiaomin , Long Yanrong , Zhong Heju , Wang Peng , Yuan Peiqiang , Zhang Xiaoling , Che Lianqiang , Feng Bin , Li Jian , Zhuo Yong , Lin Yan , Xu Shengyu , Wu De , Fang Zhengfeng
Published: May 2020

Bile acids (BA) have emerged as signalling molecules regulating intestinal physiology. The importance of intestinal microbiota in production of secondary BA, for example, lithocholic acid (LCA) which impairs enterocyte proliferation and permeability, triggered us to determine the effects of oral probiotics on intestinal BA metabolism. Piglets were weaned at 28 d of age and allocated into control (CON,n14) or probiotic (PRO,n14) group fed 50 mg ofLactobacillus plantarumdaily, and gut microbiota and BA profile were determined. To test the potential interaction of LCA with bacteria endotoxins in inducing damage of enterocytes, IPEC-J2 cells were treated with LCA, lipopolysaccharide (LPS) and LCA + LPS and expressions of genes related to inflammation, antioxidant capacity and nutrient transport were determined. Compared with the CON group, the PRO group showed lower total LCA level in the ileum and higher relative abundance of theLactobacillusgenus in faeces. In contrast, the relative abundances ofBacteroides,Clostridium_sensu_stricto_1,ParabacteroidesandRuminococcus_1, important bacteria genera in BA biotransformation, were all lower in the PRO than in the CON group. Moreover, PRO piglets had lower postprandial glucagon-like peptide-1 level, while higher glucose level than CON piglets. Co-administration of LPS and LCA led to down-regulated expression of glucose and peptide transporter genes in IPEC-J2 cells. Altogether, oralL. plantarumaltered BA profile probably by modulating relative abundances of gut microbial genera that play key roles in BA metabolism and might consequently impact glucose homoeostasis. The detrimental effect of LCA on nutrient transport in enterocytes might be aggravated under LPS challenge.
Welfare and Conflict: Policy Failure in the Indonesian Cash Transfer
Authors: SUMARTO MULYADI
Published: May 2020

Welfare policy may promote social integration and reduce social conflicts in communities. However, this study finds that the Indonesian unconditional cash transfer program stimulated multifaceted conflicts, which were accompanied by harmful social unrest. The government failed to lessen such conflicts, but community leaders successfully minimized the conflicts through informal redistribution. This redistribution reflects problematic informal-formal layering and nesting, which lead to a complicated policy failure. Employing social conflict and institutional change theoretical frameworks, this article aims at using the Indonesian cash transfer as a lens to understand how and why welfare policy causes social conflicts in communities and how the conflicts stimulate policy distortion and modification, resulting in policy failure. This policy failure reveals important theoretical implications on the nexus of conflict and institutional change.
Word association research and the L2 lexicon
Authors: Fitzpatrick Tess , Thwaites Peter
Published: May 2020

Since its modern inception in the late nineteenth century, research on word associations has developed into a large and diverse area of study, including work with both applied linguistic and psycholinguistic orientations. However, despite significant recent interest in the use of word association to investigate second language (L2) vocabulary knowledge and testing, there has until now been no systematic attempt to review the wider word association research tradition for the benefit of L2-oriented researchers and practitioners. This paper seeks to address this, drawing together linguistic research from the past 150 years, with a focus on research published since 2000. We evaluate the current state of L2 word association research, before identifying methodological and theoretical themes from a broader range of disciplinary approaches. Emerging from this, new paradigms are identified which have potential to catalyse a new phase of work for second language word association scholars, and which indicate priority foci for future work.
Chinese parents’ comparisons of siblings and adolescents’ internalizing and externalizing problems
Authors: Chen Bin-Bin , Qu Yang , Chen Xiaochen
Published: May 2020

Parents’ comparisons of siblings have been understudied among sibling research, especially in Chinese societies where the government recently relaxed its one-child policy. This study, using a two-wave longitudinal design, explored how parents’ comparisons of siblings were associated with adolescents’ internalizing and externalizing problems. Study participants were 260 Chinese adolescents who had siblings and completed questionnaires that assessed their internalizing and externalizing problems, as well as their perceptions of parents’ critical comparisons of siblings. Cross-lagged modeling analysis showed that parents’ comparisons of siblings predicted more internalizing and externalizing problems in adolescents 6 months later. Moreover, adolescents’ externalizing problems but not internalizing problems predicted more parents’ comparisons of siblings over time. These findings underscore the importance of reciprocal relations between parents’ comparisons of siblings and adolescents’ externalizing problems and the implication of cultural context in understanding associations between parental practices and adolescents’ adjustment.
“Terrible Iterations”: ReadingTesswithout Consent
Authors: Hillard Molly Clark
Published: May 2020

In the fall of 2017, a year into the current U.S. administration, a month into the #MeToo movement, I reread Adorno's 1962 essay “Commitment,” on the creation and consumption of art in an authoritarian world. I reread it at the same time that I became brave enough, and angry enough, to teachTess of the D'Urbervilles(1891) for the first time in my fifteen-year career. Adorno says that Sartre's question, “‘Is there any meaning in life when men exist who beat people until the bones break in their bodies?’ is also the question whether any art now has the right to exist” in the wake of atrocities like the Holocaust. Adorno ultimately resolves the question in the affirmative, but only at the end of an essay otherwise dedicated to the difficulties of producing literature that resists a consumerist regime. For Adorno, committed literature (that is, progressive, instrumentalized, messaged) all too often assimilates itself to the brutalities against which it protests, while autonomous literature (that is, art that exists for itself) runs the risk of degenerating into a “fetish . . . an apoliticism that is in fact deeply political” (177). In returning to bothTessand Adorno after a longish absence, I wondered whether, in spite of Adorno's overtly modernist leanings, we might nevertheless consider that certain Victorian novels manifest his concept of tensed oscillation between commitment and autonomy. Adorno suggests that certain nonrealist art forms (one of his examples is Picasso'sGuernica) neither “do” nor attempt to compel others to “do” anything instrumental, and yet such works simultaneously both illuminate and (precisely in their turning away from action) condemn systemic brutalities. We need not entirely agree with Adorno's reading ofGuernicaspecifically, nor his fetish-treatment of modernist art broadly, to entertain the idea that—even in their realist projects—certain Victorian novels also “negate empirical reality, [and] by merely existing endlessly reiterat[e systemic] guilt” (190). I'll return to this question more directly later in the essay; for now, let it lurk in the corners of my discussion ofTess.
Early Morning Equatorial Ionization Anomaly From GOLD Observations
Authors: Laskar F. I. , Eastes R. W. , Martinis C. R. , Daniell R. E. , Pedatella N. M. , Burns A. G. , McClintock W. , Goncharenko L. P. , Coster A. , Milla M. A. , Wang W. , Valladares C. E. , Codrescu M. V.
Published: May 2020

During geomagnetically quiet and solar minimum conditions, spatial variations of the early morning thermosphere‐ionosphere (TI) system are expected to be mainly governed by wave dynamics. To study the postmidnight dynamical coupling, we investigated the early morning equatorial ionization anomaly (EIA) using Global‐scale Observations of the Limb and Disk (GOLD) measurements of OI‐135.6 nm nightglow emission and global navigation satellite system (GNSS)‐based total electron content (TEC) maps. The EIA structures in the OI‐135.6 nm emission over the American landmass resemble, spatially and temporally, those observed in the GNSS‐TEC maps. The early morning EIA (EM‐EIA) crests are well separated in latitude and mostly located over the middle of South America during October–November. In February–April the crests are less separated in latitude and predominantly located over the west coast sector of South America. Whole Atmosphere Community Climate Model with thermosphere and ionosphere eXtension (WACCMX) simulations with constant solar minimum and quiet‐geomagnetic conditions show that EM‐EIA can occur globally and shows properties similar to longitudinal Wave 4 pattern. Thus, we propose that EM‐EIA is driven by dynamical changes associated with the lower atmospheric waves.
Estimating P Wave Velocity and Attenuation Structures Using Full Waveform Inversion Based on a Time Domain Complex‐Valued Viscoacoustic Wave Equation: The Method
Authors: Yang Jidong , Zhu Hejun , Li Xueyan , Ren Li , Zhang Shuo
Published: May 2020

To complement velocity distributions, seismic attenuation provides additional important information on fluid properties of hydrocarbon reservoirs in exploration seismology, as well as temperature distributions, partial melting, and water content within the crust and mantle in earthquake seismology. Full waveform inversion (FWI), as one of the state‐of‐the‐art seismic imaging techniques, can produce high‐resolution constraints for subsurface (an)elastic parameters by minimizing the difference between observed and predicted seismograms. Traditional waveform inversion for attenuation is commonly based on the standard‐linear‐solid (SLS) wave equation, in which case the quality factor (Q) has to be converted to stress and strain relaxation times. When using multiple attenuation mechanisms in the SLS method, it is difficult to directly estimate these relaxation time parameters. Based on a time domain complex‐valued viscoacoustic wave equation, we present an FWI framework for simultaneously estimating subsurface P wave velocity and attenuation distributions. Because Q is explicitly incorporated into the viscoacoustic wave equation, we directly derive P wave velocity and Q sensitivity kernels using the adjoint‐state method and simultaneously estimate their subsurface distributions. By analyzing the Gauss‐Newton Hessian, we observe strong interparameter crosstalk, especially the leakage from velocity to Q. We approximate the Hessian inverse using a preconditioned L‐BFGS method in viscoacoustic FWI, which enables us to successfully reduce interparameter crosstalk and produce accurate velocity and attenuation models. Numerical examples demonstrate the feasibility and robustness of the proposed method for simultaneously mapping complex velocity and Q distributions in the subsurface.
Locating Spatial Changes of Seismic Scattering Property by Sparse Modeling of Seismic Ambient Noise Cross‐Correlation Functions: Application to the 2008 Iwate‐Miyagi Nairiku (Mw6.9), Japan, Earthquake
Authors: Hirose Takashi , Nakahara Hisashi , Nishimura Takeshi , Campillo Michel
Published: May 2020

Locating change regions of seismic velocities and seismic scattering properties associated with volcanic activities and earthquakes is important for structural monitoring. To increase such applications, we propose to use sparse modeling to estimate spatial distributions of seismic scattering property changes. The sparse modeling is an inversion technique that enables us to estimate model parameters from a small data set with sparsity condition such asℓ1norm regularization. We apply this technique to seismic ambient noise cross‐correlation functions from 17 Hi‐net stations around the epicenter of the 2008 Iwate‐Miyagi Nairiku, Japan, earthquake (Mw=6.9). We compute waveform decoherences at the 0.5–1 Hz band and invert the waveform decoherences for the spatial distributions of seismic scattering property changes. Just after the main shock, the largest change occurred at the south of the epicenter, and the maximum change of the scattering coefficient in this region is estimated to be 0.032 km−1. The result from an ordinary linear least squares inversion with theℓ2norm regularization is almost consistent with that from the sparse modeling. Moreover, we confirm the superiority of sparse modeling in imaging with smaller data sets. Only five seismic stations that are deployed near the epicenter so as to surround the change regions are necessary to retrieve the result from 17 stations. On the other hand, in the case of theℓ2norm regularization, we need at least 15 stations. The sparse modeling will be helpful to estimate the spatial distribution of seismic scattering property changes from a small data set.
Linking Marine Biological Activity to Aerosol Chemical Composition and Cloud‐Relevant Properties Over the North Atlantic Ocean
Authors: Mansour Karam , Decesari Stefano , Facchini Maria Cristina , Belosi Franco , Paglione Marco , Sandrini Silvia , Bellacicco Marco , Marullo Salvatore , Santoleri Rosalia , Ovadnevaite Jurgita , Ceburnis Darius , O'Dowd Colin , Roberts Gregory , Sanchez Kevin , Rinaldi Matteo
Published: May 2020

The ways in which marine biological activity affects climate, by modifying aerosol properties, are not completely understood, causing high uncertainties in climate predictions. In this work, in situ measurements of aerosol chemical composition, particle number size distribution, cloud condensation nuclei (CCN), and ice‐nucleating particle (INP) number concentrations are combined with high‐resolution sea surface chlorophyll‐a concentration (CHL) and back‐trajectory data to elucidate the relationship between oceanic biological activity and marine aerosol. The measurements were performed during an intensive field campaign conducted in late summer (August–September) 2015 at the Mace Head Research Station (MHD). At the short time scale (1–2 months) of the experiment, we observed a clear dependency of the main aerosol physicochemical and cloud‐relevant properties on the patterns of biological activity, in specific oceanic regions with a delayed response of about 1–3 weeks. The oceanic region comprised between 47°–57°N and 14°–30°W was identified as the main source of biogenic aerosols during the campaign, with hints of some minor influence of waters up to the Greenland coast. These spatial and temporal relationships demonstrate that the marine biota influences aerosol properties under a variety of features up to the most cloud‐relevant properties. Such dependency of aerosol properties with oceanic biological activity was previously reported over the North Atlantic Ocean only for multiyear data sets, where the correlation may be enhanced by coincident seasonalities. A better knowledge of these short time scale interactions may lead to a significant improvement in understanding the ocean‐atmosphere‐cloud system, with important impacts on climate science.
Estimation of Turbulence Parameters Using ARIES ST Radar and GPS Radiosonde Measurements: First Results From the Central Himalayan Region
Authors: Jaiswal Aditya , Phanikumar D. V. , Bhattacharjee S. , Naja Manish
Published: May 2020

Turbulence in the atmosphere plays a vital role in controlling the surface, lower and upper tropospheric dynamics. Here, we have utilized a newly installed Aryabhatta Research Institute of Observational Sciences (ARIES) Stratosphere Troposphere (ST) radar at the high‐altitude subtropical site in the central Himalayan region (Nainital, 29.4°N, 79.5°E, 1793 m above mean sea level) for the first ever estimation of turbulence parameters from this unique location. We have used radar observations made in years 2017 and 2019 with simultaneous and colocated global positioning system (GPS) radiosonde observations. In this context, turbulence parameters like turbulent kinetic energy dissipation rate, and eddy diffusion coefficient due to thermal and momentum fluctuations, have been determined by using (i) wind variance, (ii) Doppler spectral width, and (iii) backscatter signal power methods as well as synergistic radiosonde measurements using Thorpe length scale method. The kinetic energy dissipation rate and eddy diffusivity coefficients were found to be as high as 10−2 m2/s3and 102.6 m2/s, respectively. Statistical distribution of turbulence parameters derived from radar and radiosonde was found to agree reasonably well in terms of measures of central tendency. The refractive index structure constant (Cn2) shows a decreasing tendency with height, and it is found to vary as large as 10−14to as small as 10−19 m−2/3. Range and temporal variation of signal‐to‐noise ratio (SNR) indicated the existence of a stable layer around 8 km height. It is also evident from the present study that the turbulence parameters at this central Himalayan region of complex terrain are higher by 1 order of magnitude than those reported from the southern part of India.
Oligocene Deformation of the Chuandian Terrane in the SE Margin of the Tibetan Plateau Related to the Extrusion of Indochina
Authors: Li Shihu , Su Tao , Spicer Robert A. , Xu Congli , Sherlock Sarah , Halton Alison , Hoke Gregory , Tian Yimin , Zhang Shitao , Zhou Zhekun , Deng Chenglong , Zhu Rixiang
Published: May 2020

Mechanisms driving the tectonic evolution of the southeast (SE) margin of Tibet include the Paleogene extrusion of the coherent Indochina lithospheric block and the continuous deformation caused by lower crustal flow since the middle Miocene. The timing and style of regional deformations are keys to determining the role of each mechanism. Fault‐bounded and fault‐controlled Cenozoic basins within the SE margin of Tibet record regional deformation, surface uplift, and variations in paleoclimate but often are poorly dated. New magnetostratigraphy and 40Ar/39Ar dating of volcanic ashes constrain precisely the timing of sedimentation within the Lühe Basin to between ~35 and 26.5 Ma. The basin is located in the Chuandian terrane along the Chuxiong fault, which lies ~70 km north of, and parallel to, the Ailao Shan‐Red River fault. The asymmetric syncline of the Lühe Basin suggests syncontractional sedimentation, and the basal age of the basin represents the initiation of the Chuxiong fault and crustal shortening at ~35 Ma. This is coincident with the onset of the Ailao Shan‐Red River fault and supports a kinematic link between them. Our study suggests that, like the Ailao Shan‐Red River fault, the Chuxiong fault is a Paleogene transpressional structure that developed during the extrusion and clockwise rotation of Indochina around the Eastern Himalayan Syntaxis, which caused the late Paleogene deformation and surface uplift of the Chuandian terrane and Indochina. Our revised chronostratigraphy of the Lühe Basin provides further evidence that many of the “Neogene” sedimentary basins in the SE margin of Tibet may be much older than previously thought.
Reservoirs Modify River Thermal Regime Sensitivity to Climate Change: A Case Study in the Southeastern United States
Authors: Cheng Yifan , Voisin Nathalie , Yearsley John R. , Nijssen Bart
Published: May 2020

Seasonal thermal stratification in reservoirs changes the thermal regime of regulated river systems as well as stream temperature responses to climate change. Cold releases from the reservoir hypolimnion can depress downstream river temperature during warm seasons. Recent large‐scale climate change studies on stream temperature have largely ignored reservoir thermal stratification. In this study, we used established models to develop a framework which considers water demand and reservoir regulation with thermal stratification and applied this model framework to the southeastern United States. About half of all 271 reservoirs in our study area retain strong thermal stratification by the 2080s (2070–2099) under RCP8.5 even as median residence times decrease to 60 days from 69 days in the historic period (1979–2010). Reservoir impacts on downstream temperatures become slightly weaker in the future because of higher air temperature and stronger solar radiation. We defined a “cooling potential” to quantify the thermal energy that a water body can absorb before exceeding a water temperature threshold. In the future, higher river temperatures will reduce the cooling potential for all river segments, but more so for river segments minimally impacted by thermal stratification. Reservoir impacts on cooling potential remain strong for river segments downstream of reservoirs with strong thermal stratification. We conducted a sensitivity analysis to evaluate the robustness of our findings to errors in the hydrological simulations. Although river segments subject to reservoir regulation are more sensitive to errors in hydrology than those without regulation impacts, our overall findings do not materially change due to these errors.
AquaSat Gives Water Quality Researchers New Eyes in the Sky
Authors: Kelvey Jon
Published: May 2020

A new data set combining sample data and remote sensing could give scientists the power to make accurate predictions at a global scale.
Effects of Gentle Topography on Forest‐Atmosphere Gas Exchanges and Implications for Eddy‐Covariance Measurements
Authors: Chen Bicheng , Chamecki Marcelo , Katul Gabriel G.
Published: May 2020

The interpretation of tower‐based eddy‐covariance (EC) turbulent flux measurements above forests hinges on three key assumptions: (1) steadiness in the flow statistics, (2) planar homogeneity of scalar sources or sinks, and (3) planar homogeneity in the flow statistics. Large eddy simulations (LESs) were used to control the first two so as to explore the break‐down of the third for idealized and real gentle topography such as those encountered in Amazonia. The LES runs were conducted using uniformly distributed sources inside homogeneous forests covering complex terrain to link the spatial patterns of scalar turbulent fluxes to topographic features. Results showed strong modulation of the fluxes by flow features induced by topography, including large area with negative fluxes compensating “chimney” regions with fluxes almost an order of magnitude larger than the landscape flux. Significant spatial heterogeneity persisted up to at least two canopy heights, where most eddy‐covariance measurements are performed above tall forests. A heterogeneity index was introduced to characterize and contrast different scenarios, and a topography categorization was shown to have predictive capabilities in identifying regions of negative and enhanced fluxes.
Daily Continuous River Discharge Estimation for Ungauged Basins Using a Hydrologic Model Calibrated by Satellite Altimetry: Implications for the SWOT Mission
Authors: Huang Qi , Long Di , Du Mingda , Han Zhongying , Han Pengfei
Published: May 2020

The emergence of state‐of‐the‐art satellite altimetry has provided new prospects for integrating water surface elevation (water level) measurements with a hydrologic model for river discharge estimation, which is particularly suited for poorly gauged or ungauged basins. In this context, we explored the possibility of model calibration using Jason‐2‐derived water levels, followed by SWOT (the Surface Water and Ocean Topography mission)‐like data (the combination of Landsat 5/8‐derived at‐a‐section river widths and concurrent gauged water levels). Two types of empirical formulas designed specifically for altimetry‐derived water levels and the joint use of water levels and river widths, respectively, were used to derive discharge, which was integrated with a hydrologic model (CREST‐RS). Here we present results of estimating daily continuous river discharge in narrow rivers for the upper Brahmaputra River (UBR) and Lhasa River (LR) using the developed approach independent of in situ discharge measurements. Five scenarios were performed: (1) model calibration using the Jason‐2‐derived water levels and SWOT‐like data in the UBR (scenarios I–III) and (2) model calibration using the SWOT‐like data for the LR (scenarios IV–V). Results showed that model calibration using the Jason‐2‐derived water levels could provide reasonably well‐constrained parameters for discharge estimation, with the Nash‐Sutcliffe Efficiency coefficient (NSE) reaching 0.85 during 2003–2014. For the SWOT‐like data, the NSE reached 0.85 for the UBR and 0.75 for the LR. This study highlights the potential of performing model calibration using satellite altimetry and SWOT‐like observations, which paves the way to estimate river discharge for ungauged basins globally.
Translating current basic research into future therapies for neurofibromatosis type 1
Authors: Brosseau Jean-Philippe , Liao Chung-Ping , Le Lu Q.
Published: May 2020

Neurofibromatosis type 1 (NF1) is a hereditary tumour syndrome that predisposes to benign and malignant tumours originating from neural crest cells. Biallelic inactivation of the tumour-suppressor geneNF1in glial cells in the skin, along a nerve plexus or in the brain results in the development of benign tumours: cutaneous neurofibroma, plexiform neurofibroma and glioma, respectively. Despite more than 40 years of research, only one medication was recently approved for treatment of plexiform neurofibroma and no drugs have been specifically approved for the management of other tumours. Work carried out over the past several years indicates that inhibiting different cellular signalling pathways (such as Hippo, Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase and those mediated by sex hormones) in tumour cells or targeting cells in the microenvironment (nerve cells, macrophages, mast cells and T cells) might benefit NF1 patients. In this review, we outline previous strategies aimed at targeting these signalling pathways or cells in the microenvironment, agents that are currently in clinical trials, and the latest advances in basic research that could culminate in the development of novel therapeutics for patients with NF1.
Detection of avian influenza virus: a comparative study of the in silico and in vitro performances of current RT-qPCR assays
Authors: Laconi Andrea , Fortin Andrea , Bedendo Giulia , Shibata Akihiro , Sakoda Yoshihiro , Awuni Joseph Adongo , Go-Maro Emilie , Arafa Abdelsatar , Maken Ali Ali Safar , Terregino Calogero , Monne Isabella
Published: May 2020

Avian influenza viruses (AIV) are negative sense RNA viruses posing a major threat to the poultry industry worldwide, with the potential to spread to mammals, including humans; hence, an accurate and rapid AIV diagnosis is essential. To date AIV detection relies on molecular methods, mainly RT-qPCR directed against AIV M gene segment. The evolution of AIV represents a relevant issue in diagnostic RT-qPCR due to possible mispriming and/or probe-binding failures resulting in false negative results. Consequently, RT-qPCR for AIV detection should be periodically re-assessed both in silico and in vitro. To this end, a specific workflow was developed to evaluate in silico the complementarity of primers and probes of four published RT-qPCR protocols to their target regions. The four assays and one commercially available kit for AIV detection were evaluated both for their analytical sensitivity using eight different viral dilution panels and for their diagnostic performances against clinical specimens of known infectious status. Differences were observed among the tests under evaluation, both in terms of analytical sensitivity and of diagnostic performances. This finding confirms the importance of continuously monitoring the primers and probes complementarity to their binding regions.
Topical Estrogen Treatment Augments the Vaginal Response to Escherichia coli Flagellin
Authors: Stanton Anna , Mowbray Catherine , Lanz Marcelo , Brown Karen , Hilton Paul , Tyson-Capper Alison , Pickard Robert S. , Ali Ased S. M. , Hall Judith
Published: May 2020

The female climacteric or menopausal process characterised by reduced estrogen, associates with an increased risk of recurrent urinary tract infections (rUTIs) linked to uropathogenic Escherichia coli (UPEC). Clinically, topical vaginal estrogen treatment has a prophylactic effect against such infections. The aim of this study was to investigate, in vitro, the effects of a topical estrogen treatment on vaginal epithelial responses following challenge with E.coli flagellin mimicking an UPEC challenge. Immortalised vaginal epithelial cells (VK2 E6/E7), modelling the vaginal epithelium were treated with either 4 nM 17β-estradiol (E) for seven days, 50 ng/ml E.coli flagellin (F) for 12 h, or 4 nM 17β-estradiol plus 50 ng/ml flagellin (E + F(12 h)). RNA was analysed by microarray gene profiling using the Illumina HumanHT-12 v 4 Expression Beadchip. Following E + F treatments expression of genes encoding host defence molecules including DEFβ4A, DEFB103A, LCN2 as well as those associated with keratinisation eg CNFN and SPRR family genes were significantly enhanced (P < 0.05) compared to either E or F treatments alone. Mutation of estrogen responsive elements (EREs) identified in the DEFβ4 gene promoter abolished the augmented gene expression suggesting estrogen functioned directly through a regulatory mechanism involving ESR1/2. Ingenuity pathway analyses also suggested the pro-inflammatory cytokine IL-17A to regulate the vaginal host defences during infection. Pre-treating VK2 E6/E7 cells with estrogen (4 nM) and challenging with 1L-17A & F (12 h) significantly enhanced DEFβ4, DEF103A and S100A7 expression (P < 0.05). Origins of vaginal IL-17 in vivo remain unclear, but patient biopsies support γδ T cells located within the vaginal epithelium. These data suggest that the vaginal antimicrobial response induced by flagellin activation of Toll-like Receptor 5 cell signalling is augmented following topical estrogen application.
Hydrodynamic model of directional ciliary-beat organization in human airways
Authors: Gsell Simon , Loiseau Etienne , D’Ortona Umberto , Viallat Annie , Favier Julien
Published: May 2020

In the lung, the airway surface is protected by mucus, whose transport and evacuation is ensured through active ciliary beating. The mechanisms governing the long-range directional organization of ciliary beats, required for effective mucus transport, are much debated. Here, we experimentally show on human bronchial epithelium reconstituted in-vitro that the dynamics of ciliary-beat orientation is closely connected to hydrodynamic effects. To examine the fundamental mechanisms of this self-organization process, we build a two-dimensional model in which the hydrodynamic coupling between cilia is provided by a streamwise-alignment rule governing the local orientation of the ciliary forcing. The model reproduces the emergence of the mucus swirls observed in the experiments. The predicted swirl sizes, which scale with the ciliary density and mucus viscosity, are in agreement with in-vitro measurements. A transition from the swirly regime to a long-range unidirectional mucus flow allowing effective clearance occurs at high ciliary density and high mucus viscosity. In the latter case, the mucus flow tends to spontaneously align with the bronchus axis due to hydrodynamic effects.
Decreased Na+/K+ ATPase Expression and Depolarized Cell Membrane in Neurons Differentiated from Chorea-Acanthocytosis Patients
Authors: Hosseinzadeh Zohreh , Hauser Stefan , Singh Yogesh , Pelzl Lisann , Schuster Stefanie , Sharma Yamini , Höflinger Philip , Zacharopoulou Nefeli , Stournaras Christos , Rathbun Daniel L. , Zrenner Eberhart , Schöls Ludger , Lang Florian
Published: May 2020

Loss of function mutations of the chorein-encoding gene VPS13A lead to chorea-acanthocytosis (ChAc), a neurodegenerative disorder with accelerated suicidal neuronal cell death, which could be reversed by lithium. Chorein upregulates the serum and glucocorticoid inducible kinase SGK1. Targets of SGK1 include the Na+/K+-ATPase, a pump required for cell survival. To explore whether chorein-deficiency affects Na+/K+ pump capacity, cortical neurons were differentiated from iPSCs generated from fibroblasts of ChAc patients and healthy volunteers. Na+/K+ pump capacity was estimated from K+-induced whole cell outward current (pump capacity). As a result, the pump capacity was completely abolished in the presence of Na+/K+ pump-inhibitor ouabain (100 µM), was significantly smaller in ChAc neurons than in control neurons, and was significantly increased in ChAc neurons by lithium treatment (24 hours 2 mM). The effect of lithium was reversed by SGK1-inhibitor GSK650394 (24 h 10 µM). Transmembrane potential (Vm) was significantly less negative in ChAc neurons than in control neurons, and was significantly increased in ChAc neurons by lithium treatment (2 mM, 24 hours). The effect of lithium on Vm was virtually abrogated by ouabain. Na+/K+ α1-subunit transcript levels and protein abundance were significantly lower in ChAc neurons than in control neurons, an effect reversed by lithium treatment (2 mM, 24 hours). In conclusion, consequences of chorein deficiency in ChAc include impaired Na+/K+ pump capacity.
State-space intermittent feedback stabilization of a dual balancing task
Authors: Morasso Pietro , Cherif Amel , Zenzeri Jacopo
Published: May 2020

Balancing the body in upright standing and balancing a stick on the fingertip are two examples of unstable tasks that, in spite of strong motor and sensory differences, appear to share a similar motor control paradigm, namely a state-space intermittent feedback stabilization mechanism. In this study subjects were required to perform the two tasks simultaneously, with the purpose of highlighting both the coordination between the two skills and the underlying interaction between the corresponding controllers. The experimental results reveal, in particular, that upright standing (the less critical task) is modified in an adaptive way, in order to facilitate the more critical task (stick balancing), but keeping the overall spatio-temporal signature well known in regular upright standing. We were then faced with the following question: to which extent the physical/biomechanical interaction between the two independent intermittent controllers is capable to explain the dual task coordination patterns, without the need to introduce an additional, supervisory layer/module? By comparing the experimental data with the output of a simulation study we support the former hypothesis, suggesting that it is made possible by the intrinsic robustness of both state-space intermittent feedback stabilization mechanisms.
Global responses to oxytetracycline treatment in tetracycline-resistant Escherichia coli
Authors: Møller Thea S. B. , Liu Gang , Hartman Hassan B. , Rau Martin H. , Mortensen Sisse , Thamsborg Kristian , Johansen Andreas E. , Sommer Morten O. A. , Guardabassi Luca , Poolman Mark G. , Olsen John E.
Published: May 2020

We characterized the global transcriptome of Escherichia coli MG1655:: tetA grown in the presence of ½ MIC (14 mg/L) of OTC, and for comparison WT MG1655 strain grown with 1//2 MIC of OTC (0.25 mg/L OTC). 1646 genes changed expression significantly (FDR > 0.05) in the resistant strain, the majority of which (1246) were also regulated in WT strain. Genes involved in purine synthesis and ribosome structure and function were top-enriched among up-regulated genes, and anaerobic respiration, nitrate metabolism and aromatic amino acid biosynthesis genes among down-regulated genes. Blocking of the purine-synthesis- did not affect resistance phenotypes (MIC and growth rate with OTC), while blocking of protein synthesis using low concentrations of chloramphenicol or gentamicin, lowered MIC towards OTC. Metabolic-modeling, using a novel model for MG1655 and continuous weighing factor that reflected the degree of up or down regulation of genes encoding a reaction, identified 102 metabolic reactions with significant change in flux in MG1655:: tetA when grown in the presence of OTC compared to growth without OTC. These pathways could not have been predicted by simply analyzing functions of the up and down regulated genes, and thus this work has provided a novel method for identification of reactions which are essential in the adaptation to growth in the presence of antimicrobials.
Relationship between Macroeconomic Indicators and Economic Cycles in U.S.
Authors: Iyetomi Hiroshi , Aoyama Hideaki , Fujiwara Yoshi , Souma Wataru , Vodenska Irena , Yoshikawa Hiroshi
Published: May 2020

We analyze monthly time series of 57 US macroeconomic indicators (18 leading, 30 coincident, and 9 lagging) and 5 other trade/money indexes. Using novel methods, we confirm statistically significant co-movements among these time series and identify noteworthy economic events. The methods we use are Complex Hilbert Principal Component Analysis (CHPCA) and Rotational Random Shuffling (RRS). We obtain significant complex correlations among the US economic indicators with leads/lags. We then use the Hodge decomposition to obtain the hierarchical order of each time series. The Hodge potential allows us to better understand the lead/lag relationships. Using both CHPCA and Hodge decomposition approaches, we obtain a new lead/lag order of the macroeconomic indicators and perform clustering analysis for positively serially correlated positive and negative changes of the analyzed indicators. We identify collective negative co-movements around the Dot.com bubble in 2001 as well as the Global Financial Crisis (GFC) in October 2008. We also identify important events such as the Hurricane Katrina in August 2005 and the Oil Price Crisis in July 2008. Additionally, we demonstrate that some coincident and lagging indicators actually show leading indicator characteristics. This suggests that there is a room for existing indicators to be improved.
Geological controls of giant crater development on the Arctic seafloor
Authors: Waage Malin , Serov Pavel , Andreassen Karin , Waghorn Kate A. , Bünz Stefan
Published: May 2020

Active methane seepage occurs congruent with a high density of up to 1 km-wide and 35 m deep seafloor craters (>100 craters within 700 km2 area) within lithified sedimentary rocks in the northern Barents Sea. The crater origin has been hypothesized to be related to rapid gas hydrate dissociation and methane release around 15–12 ka BP, but the geological setting that enabled and possibly controlled the formation of craters has not yet been addressed. To investigate the geological setting beneath the craters in detail, we acquired high-resolution 3D seismic data. The data reveals that craters occur within ~250–230 Myr old fault zones. Fault intersections and fault planes typically define the crater perimeters. Mapping the seismic stratigraphy and fault displacements beneath the craters we suggest that the craters are fault-bounded collapse structures. The fault pattern controlled the craters occurrences, size and geometry. We propose that this Triassic fault system acted as a suite of methane migration conduits and was the prerequisite step for further seafloor deformations triggered by rapid gas hydrate dissociation some 15–12 ka BP. Similar processes leading to methane releases and fault bounded subsidence (crater-formation) may take place in areas where contemporary ice masses are retreating across faulted bedrocks with underlying shallow carbon reservoirs.
TraPS-VarI: Identifying genetic variants altering phosphotyrosine based signalling motifs
Authors: Ulaganathan Vijay Kumar
Published: May 2020

Patient stratification and individualized therapeutic strategies rely on the established knowledge of genotype-specific molecular and cellular alterations of biological and therapeutic significance. Whilst almost all approved drugs have been developed based on the Reference Sequence protein database (RefSeq), the latest genome sequencing studies establish the substantial prevalence of non-synonymous genetic mutations in the general population, including stop-insertion and frame shift mutations within the coding regions of membrane proteins. While the availability of individual genotypes are becoming increasingly common, the biological and clinical interpretations of mutations among individual genomes is largely lagging behind. Lately, transmembrane proteins of haematopoietic (myeloid and lymphoid) derived immune cells have attracted much attention as important targets for cancer immunotherapies. As such, the signalling properties of haematological transmembrane receptors rely on the membrane-proximal phosphotyrosine based sequence motifs (TBSMs) such as ITAM (immunoreceptor tyrosine-based activation motif), ITIM (immunoreceptor tyrosine-based inhibition motif) and signal transducer and activator of transcription 3 (STAT3)-recruiting YxxQ motifs. However, mutations that alter the coding regions of transmembrane proteins, resulting in either insertion or deletion of crucial signal modulating TBSMs, remains unknown. To conveniently identify individual cell line-specific or patient-specific membrane protein altering mutations, we present the Transmembrane Protein Sequence Variant Identifier (TraPS-VarI). TraPS-VarI is an annotation tool for accurate mapping of the effect of an individual’s mutation in the transmembrane protein sequence, and to identify the prevalence of TBSMs. TraPS-VarI is a biologist and clinician-friendly algorithm with a web interface and an associated database browser (https://traps-vari.readthedocs.io/).
Egg oil from Portunus trituberculatus alleviated obesity and regulated gut microbiota in mice
Authors: Hu Shiwei , Yang Huicheng , Gao Xiang , Li Shijie , Jiang Wei , Liu Yu
Published: May 2020

Egg oil from Portunus trituberculatus (Pt-egg oil) can overcome insulin resistance resulting from abundant bioactive lipids. However, its effects on obesity and gut microbiota were unclear. Here, we evaluated whether Pt-egg oil could improve obesity and gut microbiota or not in high-fat diet feeding mice. Results exhibited that Pt-egg oil markedly reduced body weight and adipose weight gain, improved lipid accumulation and circulatory cytokines, inhibited epididymal adipose cell size. Moreover, Pt-egg oil modified gut microbiota, involving decreases in the ratio of Firmicutes to Bacteroidetes, Proteobacteria, Actinobacteria, and increase in Verrucomicrobia phylum. Pt-egg oil reduced serum and fecal lipopolysaccharide (LPS) levels and down-regulated Toll-like receptor 4 pathway in both epididymal adipose and liver tissues. Meanwhile, Pt-egg oil increased short chain fatty acids and up-regulated of G-protein-coupled receptors in both epididymal adipose and liver tissues. These suggest that Pt-egg oil could be alternative food supplement for the prophylactic effects on anti-obesity and improvement in human gut health.
On the Effects of Mechanical Stress of Biological Membranes in Modeling of Swelling Dynamics of Biological Systems
Authors: Khmelinskii Igor , Makarov Vladimir I.
Published: May 2020

We highlight mechanical stretching and bending of membranes and the importance of membrane deformations in the analysis of swelling dynamics of biological systems, including cells and subcellular organelles. Membrane deformation upon swelling generates tensile stress and internal pressure, contributing to volume changes in biological systems. Therefore, in addition to physical (internal/external) and chemical factors, mechanical properties of the membranes should be considered in modeling analysis of cellular swelling. Here we describe an approach that considers mechanical properties of the membranes in the analysis of swelling dynamics of biological systems. This approach includes membrane bending and stretching deformations into the model, producing a more realistic description of swelling. We also discuss the effects of membrane stretching on swelling dynamics. We report that additional pressure generated by membrane bending is negligible, compared to pressures generated by membrane stretching, when both membrane surface area and volume are variable parameters. Note that bending deformations are reversible, while stretching deformation may be irreversible, leading to membrane disruption when they exceed a certain threshold level. Therefore, bending deformations need only be considered in reversible physiological swelling, whereas stretching deformations should also be considered in pathological irreversible swelling. Thus, the currently proposed approach may be used to develop a detailed biophysical model describing the transition from physiological to pathological swelling mode.