bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon balance and fire emissions in Andean cypress (Austrocedrus chilensis) forests of Patagonia, Argentina
Authors: Defossé Guillermo Emilio , Godoy María Marcela , Bertolin María Lila
Published: June 2020

Wildfires are disturbances that affect forest structure and dynamics. Forests and the atmosphere interact in different ways; one is by emitting carbon (C) through wildfires and recapturing it by photosynthesis of regrowing vegetation. Estimation of C emissions and uptake allows monitoring and inventorying C at stand, landscape, or regional levels. We indirectly estimated C and other greenhouse gas emissions and uptake following Intergovernmental Panel on Climate Change (IPCC) guidelines, and also using growth curves derived from real data, in three burned pure Andean cypress (Austrocedrus chilensis) stands in Patagonia, Argentina. The sites, termed INTA (humid), LACO (mesic) and CECE (xeric), were burned on different dates (1987, INTA; 1999, CECE; 2008, LACO). Nearby unburned stands with similar structural and floristic characteristics were used as analogues to make our estimations. Carbon losses represented 245, 225, and 215t CO2 ha−1 for CECE, INTA and LACO respectively. Amount of carbon sequestered by post-fire vegetation depended on the time-lag from fire occurrence to date of sampling, whereas C uptake rates varied in time according to differences in site environmental conditions. Andean cypress seedlings present in burned stands suggest that outside the time needed, each site may recover not only lost C but also former structure and functions.
Inhibitors and fluorescent probes for protein kinase PKAcβ and its S54L mutant, identified in a patient with cortisol producing adenoma
Authors: Nonga Olivier Etebe , Enkvist Erki , Herberg Friedrich W , Uri Asko
Published: June 2020

Recently, a mutation was discovered in the gene PRKACB encoding the catalytic subunit β of PKA (PKAcβ) from a patient with severe Cushing’s syndrome. This mutation, S54L, leads to a structural change in the glycine-rich loop of the protein. In the present study, an inhibitor with six-fold selectivity toward S54L-PKAcβ mutant over the wild-type enzyme was constructed. Moreover, we developed a fluorescent assay allowing to determine side by side the affinity of commercially available PKA inhibitors, newly synthesized compounds, and fluorescent probes toward PKAcβ and S54L-PKAcβ.
Understanding human and nature interaction outcomes for sustaining tourist destinations: An example of Jiuzhaigou Nature Reserve, China
Authors: Deng Guiping , Wang Lizhu , Tang Ya , Pan Yangdong , Cao Yong , Zhu Zhongfu , Wang Beixin , Wang Quanxi , Pang Wanting
Published: June 2020

Studying interactions of coupled human-natural system components provides better understanding of their influences on ecosystem health and improves effectiveness of managing such systems. To understand how human-nature interactions determine the sustainability of tourist destinations, using Jiuzhaigou Nature Reserve as an example, we analyzed how human-nature interactions influenced the reserve’s ecological services extraction, environmental conditions, and corresponding management actions through a historical lens. We first developed a model that represented the components and their interactions under coupled human and natural systems framework. We then summarized such interactions and their resulted environmental conditions in a time sequence. Human activities have changed Jiuzhaigou system from largely human-nature balanced to partially degraded, and then to recovered and intensively managed system during the past six decades. Such changes resulted from human-nature interactions predominantly driven by overuse of natural resources, responded to by natural components in loss of ecosystem functions, and then responded by management actions to restore the functions. The increased nutrient and sediment, modified benthic communities, and decreased travertine (crystal substrate formed by the precipitation of carbonate minerals) indicate that tourism pressure in Jiuzhaigou under the current intensive management strategy has exceeded its carrying capacity. Much more aggressive environmental friendly tourism policies are needed to sustain this valuable tourist destination. Our findings based on coupled human-natural system framework analysis have important implications for sustaining natural resources and ecological services, and the governance of both for the management of nature reserves.
Final report of EURAMET.M.G-K3 regional comparison of absolute gravimeters
Authors: Falk R , Pálinkáš V , Wziontek H , Rülke A , Val'ko M , Ullrich Ch , Butta H , Kostelecký J , Bilker-Koivula M , Näränen J , Prato A , Mazzoleni F , Kirbaş C , Coşkun  , Camp M Van , Castelein S , Bernard J D , Lothhammer A , Schilling M , Timmen L , Iacovone D , Nettis G , Greco F , Messina A A , Reudink R , Petrini M , Dykowski P , Sękowski M , Janák J , Papčo J , Engfeldt A , Steffen H
Published: June 2020

The regional key comparison of absolute gravimeters, EURAMET.M.G-K3 and the simultaneously organized additional comparison, was held in Germany at the Geodetic Observatory Wettzell of the German Federal Agency for Cartography and Geodesy in the spring of 2018.

Here we present the list of the participants who actually performed measurements during the comparison, the data submitted by the operators as well as the results of the determination of the gravity as a function of height at the comparison sites. The measurement strategy is briefly discussed and the results of the data harmonization is documented. Finally, the results of the constrained least squares adjustment are presented including the degrees of equivalence of each gravimeter and the key comparison reference values.

Main text

To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.

The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Renormalisation with SU(1, 1) coherent states on the LQC Hilbert space
Authors: Bodendorfer Norbert , Wuhrer Dennis
Published: June 2020

We present an analytic computation of an explicit renormalisation group flow for cosmological states in loop quantum gravity. A key ingredient in our analysis are Perelomov coherent states for the Lie group SU(1, 1) whose representation spaces are embedded into the standard loop quantum cosmology (LQC) Hilbert space. The SU(1, 1) group structure enters our analysis by considering a classical set of phase space functions that generates the Lie algebra

s
u

(

1
,
1

)

. We implement this Poisson algebra as operators on the LQC Hilbert space in a non-anomalous way. This task requires a rather involved ordering choice, whose existence is one of the main results of the paper. As a consequence, we can transfer recently established results on coarse graining cosmological states from direct quantisations of the above Poisson algebra to the standard LQC Hilbert space and full theory embeddings thereof. We explicitly discuss how the

s
u

(

1
,
1

)

representation spaces used in this latter approach are embedded into the LQC Hilbert space and how the

s
u

(

1
,
1

)

representation label sets a lower cut-off for the loop quantum gravity spins (=U(1) representation labels in LQC). Our results provide an explicit example of a non-trivial renormalisation group flow with a scale set by the

s
u

(

1
,
1

)

representation label and interpreted as the minimally resolved geometric scale.
Path integral Monte Carlo method for the quantum anharmonic oscillator
Authors: Mittal Shikhar , Westbroek Marise J E , King Peter R , Vvedensky Dimitri D
Published: June 2020

The Markov chain Monte Carlo (MCMC) method is used to evaluate the imaginary-time path integral of a quantum oscillator with a potential that includes a quadratic term and a quartic term whose coupling is varied by several orders of magnitude. This path integral is discretized on a time lattice on which calculations for the energy and probability density of the ground state and energies of the first few excited states are carried out on lattices with decreasing spacing to estimate these quantities in the continuum limit. The variation of the quartic coupling constant produces corresponding variations in the optimum simulation parameters for the MCMC method and in the statistical uncertainty for a fixed number of paths used for measurement. The energies and probability densities are in excellent agreement with those obtained from numerical solutions of Schrödinger’s equation. The theoretical and computational framework presented here introduces undergraduates to the path integral formulations of quantum mechanics in real time and the partition function in statistical mechanics in imaginary time. The example of the anharmonic oscillator helps to build an intuition about the MCMC method of evaluating the partition function, which can then be used to solve other problems in physics and beyond.
Dissociation and ionization of HeH+ in sub-cycle-controlled intense two-color fields
Authors: Oppermann F , Wustelt P , Florin T , Mhatre S , Gräfe S , Paulus G G , Lein M
Published: June 2020

Using quantum-mechanical, one-dimensional, non-Born–Oppenheimer simulations we study the control over the strong-field dynamics of the helium hydride molecular ion HeH+ due to interaction driven by short and strong two-color laser pulses. We calculate yields of two competing fragmentation channels: electron removal and dissociation. We find that by changing the relative phase of the two colors, we can select the dominating channel. Nuclear motion is decisive for explaining ionization in this target. Ionization yields are vastly underestimated when nuclear motion is excluded and they are substantially reduced in the heavier isotopologue HeD+. Coupling of the two lowest electronic states is crucial even for the ground-state dissociation process.
A heterogenous, time harmonic, nearly incompressible transverse isotropic finite element brain simulation platform for MR elastography
Authors: McGarry Matthew , Houten Elijah Van , Guertler Charlotte , Okamoto Ruth , Smith Daniel , Sowinski Damian , Johnson Curtis , Bayly Philip , Weaver John , Paulsen Keith
Published: June 2020

In this study, we describe numerical implementation of a heterogenous, nearly incompressible, transverse isotropic (NITI) finite element (FE) model with key advantages for use in MR elastography of fibrous soft tissue. MR elastography (MRE) estimates heterogenous property distributions from MR-measured harmonic motion fields based on assumed mechanical models of tissue response. Current MRE property estimation methods usually assume isotropic properties, which cause inconsistencies arising from model-data mismatch when anisotropy is present. In this study, we use a NITI model parameterized by a base shear modulus, shear anisotropy, tensile anisotropy, and an isotropic bulk modulus, which describes the mechanical behavior of tissues with aligned fiber structures well. Property and fiber direction heterogeneity are implemented at the level of FE Gauss points, which allows high-resolution diffusion tensor imaging (DTI) data to be incorporated easily into the model. The resulting code was validated against analytical solutions and a commercial FEM package, and is suitable for incorporation into nonlinear inversion MRE algorithms. Simulations of MRE in brain tissue with heterogeneous properties and anisotropic fiber tracts, which produced wavefields similar to experimental MRE, were generated from anatomical, DTI and MRE image data, allowing investigation of MRE inversion performance in a realistic setting where the ground truth and underlying mechanical behavior are known. Two established isotropic inversion algorithms—nonlinear inversion (NLI) and local direct inversion (LDI)—were applied to simulated MRE data. Both algorithms performed well in simple isotropic homogenous cases; however, heterogeneity cased substantial artifacts in LDI arising from violation of local homogeneity assumptions. NLI was able to recover accurate heterogenous displacement fields in the presence of measurement noise. Isotropic NLI inversion of simulated anisotropic data (generated using the NITI model) produced maps of isotropic mechanical properties with undesirable dependence on the wavefield. Local anisotropy also caused wavefield-dependent errors of 7% in nearby isotropic structures, compared to 10% in the anisotropic structures.
Nonlinear power dependence of the spectral properties of an optical parametric oscillator below threshold in the quantum regime
Authors: Shafiee Golnoush , Strekalov Dmitry V , Otterpohl Alexander , Sedlmeir Florian , Schunk Gerhard , Vogl Ulrich , Schwefel Harald G L , Leuchs Gerd , Marquardt Christoph
Published: June 2020

Photon pairs and heralded single photons, obtained from cavity-assisted parametric down conversion (PDC), play an important role in quantum communications and technology. This motivated a thorough study of the spectral and temporal properties of parametric light, both above the optical parametric oscillator (OPO) threshold, where the semiclassical approach is justified, and deeply below it, where the linear cavity approximation is applicable. The pursuit of a higher two-photon emission rate leads into an interesting intermediate regime, between above OPO threshold and very low pump power, where the OPO still operates considerably below the threshold but the nonlinear cavity phenomena cannot be neglected anymore. Here, we investigate this intermediate regime and show that the spectral and temporal properties of the photon pairs, as well as their emission rate, may significantly differ from the widely accepted linear model. The observed phenomena include frequency pulling and broadening in the temporal correlation for the down-converted optical fields. These factors need to be taken into account when devising practical applications of the high-rate cavity-assisted spontaneous PDC sources.
Polarization-resolved analysis of high-order harmonic generation in monolayer MoS2
Authors: Liu Candong , Zheng Yinghui , Zeng Zhinan , Li Ruxin
Published: June 2020

We employ a theoretical model based on the density-matrix equation in the velocity gauge to calculate high harmonic generation from monolayer MoS2. This approach incorporates the tight-binding model, enabling the full consideration of both crystal symmetry and multiple band effects. In additional to the usual odd harmonics, even harmonics are also presented in the case of observing two different polarization components, which are parallel and perpendicular to the polarization of linearly driving pulses. We detailedly analyze the crystal orientation dependence for the parallel and perpendicular components of both odd- and even-harmonics. It is found that they exhibits different modulation behavior with rotating the crystal orientation. The simulation results capture all important orientation-dependent features observed in the recent experiment, thus demonstrating that the Berry curvature of MoS2 has been appropriately considered in our proposed model. In order to facilitate analysis of the underlying mechanism, we examine the channel current in terms of the contribution from different density-matrix elements, and identify their role in the orientation modulation of high harmonics. We further use simplified one-dimensional integral model to explain the appearance of perpendicular components of even harmonics. Our analysis shows that the multi-band coupling effect is the origin of the parallel even harmonics, while the broken inversion symmetry of phase difference of momentum matrix elements along two orthogonal directions determines the perpendicular even harmonic generation. Additionally, the relationship between the concept of Berry curvature and our theoretical framework is discussed. These demonstrations show that polarization-resolved high harmonics might provide an all-optical way for imaging material’s Berry curvature.
Impact of Higgs portal on gravity-mediated production of superheavy dark matter
Authors: Chianese Marco , Fu Bowen , King Stephen F.
Published: June 2020

In the so-called Planckian Interacting Dark Matter (PIDM)
scenario, superheavy dark matter particles are produced after
inflation by gravity-mediated interactions through the freeze-in
mechanism. In the minimal PIDM model, the absence of any additional
direct coupling with Standard Model particles is assumed. However,
for scalar dark matter particles there is no symmetry that
suppresses the Higgs portal coupling. In this paper, we therefore
study the impact of a non-zero interaction with the Higgs field on
the PIDM paradigm for scalar dark matter. In particular, we fully
explore the model parameter space in order to identify the allowed
regions where the correct dark matter abundance is
achieved. Moreover, we provide the threshold value for the Higgs
portal coupling below which the corresponding production processes
are sub-dominant and the minimal PIDM scenario is preserved. For a
benchmark scalar dark matter mass of 1015 GeV, we find that the
Higgs portal coupling has to be smaller than 5.1 × 10-8
(1.1 × 10-7) for instantaneous (non-instantaneous)
reheating.
Stability of flexible thin-film metallization stimulation electrodes: analysis of explants after first-in-human study and improvement of in vivo performance
Authors: Čvančara Paul , Boretius Tim , López-Álvarez Víctor M , Maciejasz Pawel , Andreu David , Raspopovic Stanisa , Petrini Francesco , Micera Silvestro , Granata Giuseppe , Fernandez Eduardo , Rossini Paolo M , Yoshida Ken , Jensen Winnie , Divoux Jean-Louis , Guiraud David , Navarro Xavier , Stieglitz Thomas
Published: June 2020

Objective. Micro-fabricated neural interfaces based on polyimide (PI) are achieving increasing importance in translational research. The ability to produce well-defined micro-structures with properties that include chemical inertness, mechanical flexibility and low water uptake are key advantages for these devices. Approach. This paper reports the development of the transverse intrafascicular multichannel electrode (TIME) used to deliver intraneural sensory feedback to an upper-limb amputee in combination with a sensorized hand prosthesis. A failure mode analysis on the explanted devices was performed after a first-in-human study limited to 30 d. Main results. About 90% of the stimulation contact sites of the TIMEs maintained electrical functionality and stability during the full implant period. However, optical analysis post-explantation revealed that 62.5% of the stimulation contacts showed signs of delamination at the metallization-PI interface. Such damage likely occurred due to handling during explantation and subsequent analysis, since a significant change in impedance was not observed in vivo. Nevertheless, whereas device integrity is mandatory for long-term functionality in chronic implantation, measures to increase the bonding strength of the metallization-PI interface deserve further investigation. We report here that silicon carbide (SiC) is an effective adhesion-promoting layer resisting heavy electrical stimulation conditions within a rodent animal trial. Optical analysis of the new electrodes revealed that the metallization remained unaltered after delivering over 14 million pulses in vivo without signs of delamination at the metallization-PI interface. Significance. Failure mode analysis guided implant stability optimization. Reliable adhesion of thin-film metallization to substrate has been proven using SiC, improving the potential transfer of micro-fabricated neural electrodes for chronic clinical applications. (Document number of Ethical Committee: P/905/CE/2012; Date of approval: 2012–10-04)
Facet-driven formation of axial and radial In(Ga)As clusters in GaAs nanowires
Authors: Balgarkashi A , Ramanandan S P , Tappy N , Nahra M , Kim W , Güniat L , Friedl M , Morgan N , Dede D , Leran J B , Couteau C , Fontcuberta i Morral A
Published: June 2020

Embedding quantum dots in nanowires (NWs) constitutes one promising building block for quantum photonic technologies. Earlier attempts to grow InAs quantum dots on GaAs nanowires were based on the Stranski–Krastanov growth mechanism. Here, we propose a novel strain-driven mechanism to form 3D In-rich clusters on the NW sidewalls and also on the NW top facets. The focus is on ternary InGaAs nanowire quantum dots which are particularly attractive for producing single photons at telecommunication wavelengths. In(Ga)As clusters were realized on the inclined top facets and also on the {11-2} corner facets of GaAs NW arrays by depositing InAs at a high growth temperature (630 °C). High-angle annular dark-field scanning transmission electron microscopy combined with energy-dispersive x-ray spectroscopy confirms that the observed 3D clusters are indeed In-rich. The optical functionality of the as-grown samples was verified using optical technique of cathodoluminescence. Emission maps close to the NW tip shows the presence of optically active emission centers along the NW sidewalls. Our work illustrates how facets can be used to engineer the growth of localized emitters in semiconducting NWs.
Psychometric Properties of the Person-Centered Version of the Alcohol and Alcohol Problems Perceptions Questionnaire (PC-AAPPQ)
Authors: Mahmoud Khadejah F , Terhorst Lauren , Lindsay Dawn , Brager Jenna , Rodney Tamar , Sanchez Michael , Hansen Bryan R , Savage Christine L , Seale J Paul , Mitchell Ann M , Johnson J Aaron , Finnell Deborah S
Published: June 2020

Aims

Given the importance of addressing provider attitudes toward individuals with unhealthy alcohol use and the current emphasis on person-centered language to help decrease stigma and mitigate negative attitudes, the aim of this study was to evaluate the psychometric properties of a contemporary version of the Alcohol and Alcohol Problems Perception Questionnaire (AAPPQ) that uses person-centered language and addresses the spectrum of alcohol use.

Methods

The authors created a person-centered version of the AAPPQ (PC-AAPPQ) and conducted a cross-sectional study of its psychometric properties in academic settings in the Northeastern United States. The PC-AAPPQ was administered to 651 nursing students. Reliability analysis of the new instrument was performed using the total sample. Only surveys with complete data (n = 637) were randomly split into two datasets, one used for the exploratory factor analysis (EFA) (n = 310) and the other for confirmatory factor analysis (CFA) (n = 327).

Results

Compared to all the models generated from the EFA, neither the original six-factor structure nor the five-factor structure was superior to any of the other models. The results indicate that a seven-factor structure with all 30 items is the best fit for the PC-AAPPQ.

Conclusions

The PC-AAPPQ represents a positive effort to modernize the four-decade-old AAPPQ. This 30-item instrument, which adds one additional subscale, offers a means to assess providers’ attitudes using respectful wording that avoids perpetuating negative biases and reinforces efforts to affirm the worth and dignity of the population being treated.
Exploring transcriptional switches from pairwise, temporal and population RNA-Seq data using deepTS
Authors: Qiu Zhixu , Chen Siyuan , Qi Yuhong , Liu Chunni , Zhai Jingjing , Xie Shang , Ma Chuang
Published: June 2020

Transcriptional switch (TS) is a widely observed phenomenon caused by changes in the relative expression of transcripts from the same gene, in spatial, temporal or other dimensions. TS has been associated with human diseases, plant development and stress responses. Its investigation is often hampered by a lack of suitable tools allowing comprehensive and flexible TS analysis for high-throughput RNA sequencing (RNA-Seq) data. Here, we present deepTS, a user-friendly web-based implementation that enables a fully interactive, multifunctional identification, visualization and analysis of TS events for large-scale RNA-Seq datasets from pairwise, temporal and population experiments. deepTS offers rich functionality to streamline RNA-Seq-based TS analysis for both model and non-model organisms and for those with or without reference transcriptome. The presented case studies highlight the capabilities of deepTS and demonstrate its potential for the transcriptome-wide TS analysis of pairwise, temporal and population RNA-Seq data. We believe deepTS will help research groups, regardless of their informatics expertise, perform accessible, reproducible and collaborative TS analyses of large-scale RNA-Seq data.
Engineering monoclonal antibody-based contraception and multipurpose prevention technologies†
Authors: Anderson Deborah J , Politch Joseph A , Cone Richard A , Zeitlin Larry , Lai Samuel K , Santangelo Philip J , Moench Thomas R , Whaley Kevin J
Published: June 2020

Sexually transmitted infections are highly prevalent, and over 40% of pregnancies are unplanned. We are producing new antibody-based multipurpose prevention technology products to address these problems and fill an unmet need in female reproductive health. We used a Nicotiana platform to manufacture monoclonal antibodies against two prevalent sexually transmitted pathogens, HIV-1 and HSV-2, and incorporated them into a vaginal film (MB66) for preclinical and Phase 1 clinical testing. These tests are now complete and indicate that MB66 is effective and safe in women. We are now developing an antisperm monoclonal antibody to add contraceptive efficacy to this product. The antisperm antibody, H6-3C4, originally isolated by Shinzo Isojima from the blood of an infertile woman, recognizes a carbohydrate epitope on CD52g, a glycosylphosphatidylinositol-anchored glycoprotein found in abundance on the surface of human sperm. We engineered the antibody for production in Nicotiana; the new antibody which we call “human contraception antibody,” effectively agglutinates sperm at concentrations >10 μg/ml and maintains activity under a variety of physiological conditions. We are currently seeking regulatory approval for a Phase 1 clinical trial, which will include safety and “proof of principle” efficacy endpoints. Concurrently, we are working with new antibody production platforms to bring the costs down, innovative antibody designs that may produce more effective second-generation antibodies, and delivery systems to provide extended protection.
Biomarkers in psychiatry: a clinician’s viewpoint
Authors: Mahmood Tariq
Published: June 2020

Introduction

The dearth of biomarkers limits the precision of our research into pathogenesis of psychiatric disorders and has slowed down the development of new drugs. In clinical practice, it undermines the validity of psychiatric diagnoses and hampers the delivery of personalized treatment.

Sources of data

The data quoted in this paper are gathered from a range of sources encompassing scientific and journalistic both in print and electronic.

Areas of agreement

Availability of clinically useful biomarkers will improve the prognosis and outcome of psychiatric patients by helping in early diagnosis and delivery of individualized treatment.

Areas of controversy

The cross-sectional and longitudinal observation of psychopathology is the bedrock of current clinical practice. Are psychiatric biomarkers advanced enough to supplant it?

Growing points

The need for biomarkers of psychiatric disorders has become more acute with the advent of new treatments which require precision and an individualized approach.

Areas timely for developing research

Identification and deployment of intermediate phenotypes in classification, research and clinical practice of psychiatry.
Improved relapse recovery in paediatric compared to adult multiple sclerosis
Authors: Chitnis Tanuja , Aaen Greg , Belman Anita , Benson Leslie , Gorman Mark , Goyal Manu S , Graves Jennifer S , Harris Yolanda , Krupp Lauren , Lotze Timothy , Mar Soe , Ness Jayne , Rensel Mary , Schreiner Teri , Tillema Jan-Mendelt , Waubant Emmanuelle , Weinstock-Guttman Bianca , Roalstad Shelly , Rose John , Weiner Howard L , Casper T Charles , Rodriguez Moses ,   for the US Network of Paediatric Multiple Sclerosis Centers
Published: June 2020

Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack. Adult patients with multiple sclerosis (n = 632) were identified from the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham study (CLIMB), and paediatric patients (n = 132) from the US Network of Paediatric Multiple Sclerosis Centers (NPMSC) registry. Change in EDSS was defined as the difference in EDSS between attack and follow-up. Change in EDSS at follow-up compared to baseline was significantly lower in children compared to adults (P = 0.001), as were several functional system scores. Stratification by decade at onset for change in EDSS versus age found for every 10 years of age, EDSS recovery is reduced by 0.15 points (P < 0.0001). A larger proportion of children versus adults demonstrated improvement in EDSS following an attack (P = 0.006). For every 10 years of age, odds of EDSS not improving increase by 1.33 times (P < 0.0001). Younger age is associated with improved recovery from relapses. Age-related mechanisms may provide novel therapeutic targets for disability accrual in multiple sclerosis.
Gut metagenomics-derived genes as potential biomarkers of Parkinson’s disease
Authors: Qian Yiwei , Yang Xiaodong , Xu Shaoqing , Huang Pei , Li Binyin , Du Juanjuan , He Yixi , Su Binghua , Xu Li-Ming , Wang Liang , Huang Ruocheng , Chen Shengdi , Xiao Qin
Published: June 2020

Identification of the gut microbiome compositions associated with disease has become a research focus worldwide. Emerging evidence has revealed the presence of gut microbiota dysbiosis in Parkinson’s disease. In this study, we aimed to identify the gut microbiome associated with Parkinson’s disease and subsequently to screen and to validate potential diagnostic biomarkers of Parkinson’s disease. This case-control study investigated gut microbial genes in faeces from 40 volunteer Chinese patients with Parkinson’s disease and their healthy spouses using shotgun metagenomic sequencing. Furthermore, the identified specific gut microbial gene markers were validated with real-time PCR in an independent Chinese cohort of 78 Parkinson’s disease patients, 75 control subjects, 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease. We developed the first gut microbial gene catalogue associated with Parkinson’s disease. Twenty-five gene markers were identified that distinguished Parkinson’s disease patients from healthy control subjects, achieving an area under the receiver operating characteristic curve (AUC) of 0.896 (95% confidence interval: 83.1–96.1%). A highly accurate Parkinson’s disease index, which was not influenced by disease severity or Parkinson’s disease medications, was created. Testing these gene markers using quantitative PCR distinguished Parkinson’s disease patients from healthy controls not only in the 40 couples (AUC = 0.922, 95% confidence interval: 86.4–98.0%), but also in an independent group of 78 patients with Parkinson’s disease and 75 healthy control subjects (AUC = 0.905, 95% confidence interval: 86.0–95.1%). This classifier also performed a differential diagnosis power in discriminating these 78 patients with Parkinson’s disease from a cohort of 40 patients with multiple system atrophy and 25 patients with Alzheimer’s disease based on the panel of 25 biomarkers. Based on our results, the identified Parkinson’s disease index based on the gene set from the gut microbiome may be a potential diagnostic biomarker of Parkinson’s disease.
A novel regulatory loop miR-101/ANXA2/EGR1 mediates malignant characteristics of liver cancer stem cells
Authors: Ma Sai , Cheng Junping , Wang Haiyan , Ding Ningling , Zhou Feng , Ji Runing , Zhu Li , Zhu Chuanwu , Pan Yunzhi
Published: June 2020

Increasing evidence suggests that liver cancer stem cells (LCSCs) are the cellular determinants that promote tumor recurrence and metastases. Aberrantly expressed miRNAs were identified in LCSCs and found to play a significant role in modulating biological characteristics of LCSCs. In this study, we implemented miRNA microarrays in CD133+ LCSCs and found miR-101 expression was downregulated. Increasing miR-101 expression repressed the metastasis and tumorigenic potential in LCSCs. Further investigations showed that ANXA2 was a novel target of miR-101. And we revealed that ANXA2 plays a critical role in acceleration of cell cycle and enhancing the migration and invasion abilities of LCSCs. Elevated ANXA2 increased activation of extracellular signal-regulated kinase (ERK) which regulated SOX2 and cell cycle-related kinases. Moreover, ERK phosphorylation inhibited the expression of early growth response 1 (EGR1) which in turn restrained the transcription of miR-101. In vivo experiments, overexpression of miR-101 produced potent inhibitory effects on the growth of LCSCs xenograft tumors as well as ANXA2 knockdown. Taken together, our findings suggest a novel regulatory loop miR-101/ANXA2/EGR1 in LCSCs and may serve as potential therapeutic targets in liver cancer.
DUOX2 promotes the progression of colorectal cancer cells by regulating the AKT pathway and interacting with RPL3
Authors: Zhang Xue , Han Jing , Feng Li , Zhi Lianghui , Jiang Da , Yu Bin , Zhang Zhenya , Gao Bo , Zhang Cong , Li Meng , Zhao Lianmei , Wang Guiying
Published: June 2020

Dual oxidase 2 (DUOX2) is an important regulatory protein in the organic process of thyroid hormone iodine. Mounting evidence suggests that DUOX2 plays a crucial role in the occurrence and development of cancers. However, the function and mechanism of DUOX2 in colorectal cancer (CRC) have not been fully clarified. In the present study, the relationship between the expression of DUOX2 and the clinicopathological features and prognosis of CRC patients was analyzed. Furthermore, the effects of DUOX2 on proliferation and invasion in vitro and in vivo were examined. DUOX2-associated proteins were identified by immunoprecipitation (IP). Next-generation sequencing detection was performed to illustrate the mechanism of DUOX2 in CRC cells. It was found that the expression levels of DUOX2 in metastatic sites were significantly higher than those in primary tumor tissues, and this was demonstrated to be associated with poor prognosis. The knockdown of DUOX2 inhibited the invasion and migration of CRC cells. Furthermore, DUOX2 regulated the stability of ribosomal protein uL3 (RPL3) by affecting the ubiquitination status of RPL3, and the invasion and migration ability of DUOX2 can be reversed by the overexpression of RPL3. The downregulation of DUOX2 can affect the expression level of a large number of genes, and a number of these are enriched in the PI3K–AKT pathway. Some of the changes caused by DUOX2 can be reversed by RPL3. In summary, DUOX2 exhibits a significantly higher expression in CRC tumor samples, and facilitates the invasion and metastasis ability of CRC cells by interacting with RPL3.
Quantifying Genetic and Environmental Influence on Gray Matter Microstructure Using Diffusion MRI
Authors: Baxi Madhura , Di Biase Maria A , Lyall Amanda E , Cetin-Karayumak Suheyla , Seitz Johanna , Ning Lipeng , Makris Nikos , Rosene Douglas , Kubicki Marek , Rathi Yogesh
Published: June 2020

Early neuroimaging work in twin studies focused on studying genetic and environmental influence on gray matter macrostructure. However, it is also important to understand how gray matter microstructure is influenced by genes and environment to facilitate future investigations of their influence in mental disorders. Advanced diffusion MRI (dMRI) measures allow more accurate assessment of gray matter microstructure compared with conventional diffusion tensor measures. To understand genetic and environmental influence on gray matter, we used diffusion and structural MRI data from a large twin and sibling study (N = 840) and computed advanced dMRI measures including return to origin probability (RTOP), which is heavily weighted toward intracellular and intra-axonal restricted spaces, and mean squared displacement (MSD), more heavily weighted to diffusion in extracellular space and large cell bodies in gray matter. We show that while macrostructural features like brain volume are mainly genetically influenced, RTOP and MSD can together tap into both genetic and environmental influence on microstructure.
Studies of Human Twins Reveal Genetic Variation That Affects Dietary Fat Perception
Authors: Lin Cailu , Colquitt Lauren , Wise Paul , Breslin Paul A S , Rawson Nancy E , Genovese Federica , Maina Ivy , Joseph Paule , Fomuso Lydia , Slade Louise , Brooks Dennis , Miclo Aurélie , Hayes John E , Sullo Antonio , Reed Danielle R
Published: June 2020

To learn more about the mechanisms of human dietary fat perception, we asked 398 human twins to rate the fattiness and how much they liked 6 types of potato chips that differed in triglyceride content (2.5%, 5%, 10%, and 15% corn oil); reliability estimates were obtained from a subset (n = 50) who did the task twice. Some chips also had a saturated long-chain fatty acid (FA; hexadecanoic acid, 16:0) added (0.2%) to evaluate its effect on fattiness and liking. We computed the heritability of these measures and conducted a genome-wide association study (GWAS) to identify regions of the genome that co-segregate with fattiness and liking. Perceived fattiness of and liking for the potato chips were reliable (r = 0.31–0.62, P < 0.05) and heritable (up to h2 = 0.29, P < 0.001, for liking). Adding hexadecanoic acid to the potato chips significantly increased ratings of fattiness but decreased liking. Twins with the G allele of rs263429 near GATA3-AS1 or the G allele of rs8103990 within ZNF729 reported more liking for potato chips than did twins with the other allele (multivariate GWAS, P < 1 × 10–5), with results reaching genome-wide suggestive but not significance criteria. Person-to-person variation in the perception and liking of dietary fat was 1) negatively affected by the addition of a saturated FA and 2) related to inborn genetic variants. These data suggest that liking for dietary fat is not due solely to FA content and highlight new candidate genes and proteins within this sensory pathway.
Transient Effects of Cyclophosphamide on Basal Cell Proliferation of Olfactory Epithelia
Authors: Joseph Kyle B , Awadallah Nora , Delay Eugene R , Delay Rona J
Published: June 2020

Cancer is often treated with broad-spectrum cytotoxic drugs that not only eradicate cancerous cells but also have detrimental side effects. One of these side effects, disruption of the olfactory system, impedes a patient’s ability to smell, perceive flavor, and ultimately may interfere with their nutritional intake and recovery from cancer. Recent studies reported that the chemotherapy drug, cyclophosphamide (CYP), can damage gustatory epithelia and disrupt cell proliferation in olfactory epithelia. In this study, we asked if CYP altered globose and horizontal basal cell proliferation in the murine main olfactory epithelium (MOE) and vomeronasal organ (VNO). We used antibodies for Ki67, a marker strictly associated with cell proliferation, and Keratin 5, a marker for the cytoskeleton of horizontal basal cells. Our results revealed a significant CYP-induced decrease in the number of proliferative cells in both epithelia, especially globose basal cells in the MOE, within the first 1–2 days postinjection. Recovery of cell renewal was apparent 6 days after injection. The immunohistochemical markers showed significantly higher levels of globose and horizontal basal cell proliferation in CYP-injected mice at 14 and 30 days postinjection compared with control mice. The prolonged proliferative activation of globose and horizontal basal cells suggests that, besides altering proliferation of olfactory epithelia, the epithelial substrate needed for successful cell renewal may be adversely affected by CYP.
On Performance Improvement Of Reversible Data Hiding With Contrast Enhancement
Authors: Chen Haishan , Yuan Junying , Hong Wien , Ni Jiangqun , Chen Tung-Shou
Published: June 2020

Reversible data hiding (RDH) with contrast enhancement (RDH-CE) is a special type of RDH in improving the subjective visual perception by enhancing the image contrast during the process of data embedding. In RDH-CE, data hiding is achieved via pairwise histogram expansion, and the embedding rate can be increased by performing multiple cycles of histogram expansions. However, when embedding rate gets high, human visible image degradation is observed. Previous work designed an upper bound of the embedding level for RDH-CE, which effectively avoids image over-sharping but offers limited embedding capacity. In this paper, a better tunable bound is designed to enhance the embedding capacity of RDH-CE by exploiting the characteristics of histogram distribution. Furthermore, the objective distortion introduced by histogram pre-shifting is minimized when the embedding level is no more than the upper bound, and the human visible degradation is minimized when the embedding level exceeds the limitation of the proposed upper bound. Experimental results validate that the proposed method provides appropriate upper bound of the embedding level, increases the effective embedding capacity and offers better image contrast.
Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1
Authors: Ouerd Sofiane , Idris-Khodja Noureddine , Trindade Michelle , Ferreira Nathanne S , Berillo Olga , Coelho Suellen C , Neves Mario F , Jandeleit-Dahm Karin A , Paradis Pierre , Schiffrin Ernesto L
Published: June 2020

Aims

NADPH oxidase (NOX) 1 but not NOX4-dependent oxidative stress plays a role in diabetic vascular disease, including atherosclerosis. Endothelin (ET)-1 has been implicated in diabetes-induced vascular complications. We showed that crossing mice overexpressing human ET-1 selectively in endothelium (eET-1) with apolipoprotein E knockout (Apoe−/−) mice enhanced high-fat diet-induced atherosclerosis in part by increasing oxidative stress. We tested the hypothesis that ET-1 overexpression in the endothelium would worsen atherosclerosis in type 1 diabetes through a mechanism involving NOX1 but not NOX4.

Methods and results

Six-week-old male Apoe−/− and eET-1/Apoe−/− mice with or without Nox1 (Nox1−/y) or Nox4 knockout (Nox4−/−) were injected intraperitoneally with either vehicle or streptozotocin (55 mg/kg/day) for 5 days to induce type 1 diabetes and were studied 14 weeks later. ET-1 overexpression increased 2.5-fold and five-fold the atherosclerotic lesion area in the aortic sinus and arch of diabetic Apoe−/− mice, respectively. Deletion of Nox1 reduced aortic arch plaque size by 60%; in contrast, Nox4 knockout increased lesion size by 1.5-fold. ET-1 overexpression decreased aortic sinus and arch plaque alpha smooth muscle cell content by ∼35% and ∼50%, respectively, which was blunted by Nox1 but not Nox4 knockout. Reactive oxygen species production was increased two-fold in aortic arch perivascular fat of diabetic eET-1/Apoe−/− and eET-1/Apoe−/−/Nox4−/− mice but not eET-1/Apoe−/−/Nox1y/− mice. ET-1 overexpression enhanced monocyte/macrophage and CD3+ T-cell infiltration ∼2.7-fold in the aortic arch perivascular fat of diabetic Apoe−/− mice. Both Nox1 and Nox4 knockout blunted CD3+ T-cell infiltration whereas only Nox1 knockout prevented the monocyte/macrophage infiltration in diabetic eET-1/Apoe−/− mice.

Conclusion

Endothelium ET-1 overexpression enhances the progression of atherosclerosis in type 1 diabetes, perivascular oxidative stress, and inflammation through NOX1.
A Multiscale Characterization of Two Tropical Embiopteran Species: Nano- and Microscale Features of Silk, Silk-Spinning Behavior, and Environmental Correlates of their Distributions
Authors: Shenoy Samantha , Ing Keilyn , Barber Richard P , Rooks Edward C , Edgerly Janice S
Published: June 2020

Embioptera display the unique ability to spin silk with their front feet to create protective domiciles. Their body form is remarkably uniform throughout the order, perhaps because they all live within the tight confines of silken tubes. This study contributes to an understanding of the ecology of Embioptera, an order that is rarely studied in the field. We conducted a census to quantify the habitats of two species with overlapping distributions on the tropical island of Trinidad in a search for characteristics that might explain their distinct ecologies. One species, Antipaluria urichi (Saussure) (Embioptera: Clothodidae), lives in larger colonies with more expansive silk in habitats throughout the island, especially in the rainforest of the Northern Range Mountains. The other, Pararhagadochir trinitatis (Saussure) (Embioptera: Scelembiidae), was found only in lowland locations. We quantified silk-spinning behavior and productivity of the two species and found that A. urichi spins thicker silk sheets per individual and emphasizes spin-steps that function to create a domicile that is more expansive than that produced by P. trinitatis. Their silks also interact differently when exposed to water: the smaller-diameter silk fibers of P. trinitatis form more continuous films on the surface of the domicile after being wetted and dried than that seen in A. urichi silk. This tendency gives P. trinitatis silk a shiny appearance in the field compared to the more cloth-like silk of A. urichi. How these silks function in the field and if the differences are partially responsible for the distinct distributions of the two species remain to be determined.
J-Mart: aortic valve replacement with Florida sleeve aortic root reconstruction
Authors: Jeng Eric I , Martin Tomas D
Published: June 2020

We highlight a technique combining an aortic valve replacement with the Florida sleeve repair. The patient is a 68-year-old man who had a 48-mm aortic root aneurysm and a 57-mm ascending aorta, presenting with symptomatic tri-leaflet severe aortic valve stenosis. He underwent a hemiarch, aortic valve replacement and Florida sleeve aortic root reconstruction. The patient recovered uneventfully and is now, at over 1 year postoperation, without evidence of recurrent aortic pathology.