bluuebunny/crossref_metadata_2025 huggingface dataset:
Editorial
Authors: Barrett Steve
Published: May 2021

Hydrogen refueling infrastructure is of course critical to the broad deployment of fuel cell electric vehicles, from passenger FCEVs to trucks, buses and other industrial vehicles. Rolling out networks of hydrogen refueling stations is an expensive business, which requires partnerships and alliances to achieve in any meaningful way.
Fetal neuroaxonal dystrophy: a further etiology of fetal akinesia
Authors: Fallet-Bianco C , Hargitai B , Bonasoni P , Guimiot F , Yacoubi MT
Published: May 2021

Neuroaxonal Dystrophies (NAD) are neurodegenerative diseases characterized by axonal “spheroids” occurring in different age groups. The identification of mutations delineated new molecular entities in these disorders. We report neuropathological data of a new form of NAD, characterized by a precocious prenatal onset, different from classical and conatal Infantile Neuroaxonal Dystrophy (INAD).

We studied 5 fetuses examined after pregnancy termination and 2 term neonates deceased just after birth, 4/7 born from consanguineous parents. All subjects presented severe fetal akinesia sequence with microcephaly. In 4/7 cases, a molecular study was performed. In all cases, “spheroids” with typical immunohistochemical features were identified, with variable spreading in the central and peripheral nervous system. Basal ganglia, brainstem, cerebellum, and spinal cord involvement was constant. Associated CNS malformations, unusual in INAD, were associated including hydrocephalus (2), callosal agenesis/hypoplasia (2), olfactory agenesis (1), cortical (3) and retinal (1) anomalies. None of the cases demonstrated mutations in PLA2G6, found in INAD. The clinical and neuropathological features of these fetal cases are different from those of “classical” INAD. The absence of mutations in PLA2G6, in addition, suggests that the fetal NAD is a new entity, distinct from INAD, with different molecular basis. Associated malformations suggest a wide phenotypic spectrum and probable genetic heterogeneity. Finally, fetal NAD is an additional etiology of fetal akinesia.

LEARNING OBJECTIVES

This presentation will enable the learner to:

Diagnose this rare form of neuroaxonal dystrophy (NAD) occurring precociously, in the fetal life, as soon as the second trimester, different from the infantile form of NAD.

1.

Describe the phenotypic spectrum of this fetal NAD; fetal akinesia sequence, microcephaly and various brain malformations, different from the “classical” and conatal forms of infantile neuroaxonal dystrophy.

2.

Consider this etiology in the diagnosis of fetal akinesia sequence.
The tissue proteome of dorsal root ganglia in Friedreich ataxia
Authors: Koeppen AH , Travis AM , Qian J , Mazurkiewicz JE , Gelman BB , Pelech S , Sutter C
Published: May 2021

Dorsal root ganglia (DRG) at all levels of the spinal cord are a prominent target of Friedreich ataxia (FA). The lesions include hypoplasia of neurons, proliferation of satellite cells, infiltration by IBA- 1-reactive monocytes, and formation of residual nodules. Paucity and smallness of DRG neurons account for the lack of large myelinated axons in dorsal roots and sensory peripheral nerves. The lack of myelin in dorsal roots can be attributed to low levels of neuregulin 1 type III (NRG1[III]). Lysates of 13 DRG of genetically confirmed FA patients were analyzed by antibody microarray with 878 different validated antibodies that target structural and signaling proteins, and by Western blots. KIT and mTOR, two proteins involved in cellular proliferation, were significantly upregulated in the DRG of FA. KIT is a transmembrane receptor that dimerizes when it binds two molecules of stem cell factor (SCF) in its extracellular domain and becomes activated as protein tyrosine kinase. Immunohistochemistry with anti-KIT generated reaction product in satellite cells of normal DRG and prominent labeling of these cells in FA that co-localized with SCF on double- label immunofluorescence; SCF was present in S100-positive satellite cells rather than monocytes. Immunohistochemical reaction product of mTOR and other mTOR complex proteins, such as hamartin (TSC1), tuberin (TSC2), raptor (mTOR complex 1) and rictor (mTOR complex 2) was also present in satellite cells of normal DRG and DRG of FA. Antibodies to two downstream proteins that are considered to be indicators of mTOR activity, P70 S6K and 4E-binding protein 1, revealed no reaction product in DRG of FA. TSC1, TSC2, and mTOR are best known from their roles in tuberous sclerosis, but expression of these proteins, and KIT, in DRG may contribute to signaling cascades underlying the proliferation of satellite cells in FA.

LEARNING OBJECTIVES

This presentation will enable the learner to:

1.

Discuss cellular proliferation in the pathogenesis of the DRG lesion in Friedreich ataxia

CONFLICT OF INTEREST

AHK is a consultant to PTC Therapeutics of South Plainfield, NJ USA. SP and CS are majority owners of Kinexus.
Lyapunov exponent of random dynamical systems on the circle
Authors: MALICET DOMINIQUE
Published: May 2021

We consider products of an independent and identically distributed sequence in a set
$\{f_1,\ldots ,f_m\}$
of orientation-preserving diffeomorphisms of the circle. We can naturally associate a Lyapunov exponent
$\lambda $
. Under few assumptions, it is known that
$\lambda \leq 0$
and that the equality holds if and only if
$f_1,\ldots ,f_m$
are simultaneously conjugated to rotations. In this paper, we state a quantitative version of this fact in the case where
$f_1,\ldots ,f_m$
are
$C^k$
perturbations of rotations with rotation numbers
$\rho (f_1),\ldots ,\rho (f_m)$
satisfying a simultaneous diophantine condition in the sense of Moser [On commuting circle mappings and simultaneous diophantine approximations. Math. Z.205(1) (1990), 105–121]: we give a precise estimate of
$\lambda $
(Taylor expansion) and we prove that there exist a diffeomorphism g and rotations
$r_i$
such that
$\mbox {dist}(gf_ig^{-1},r_i)\ll |\lambda |^{{1}/{2}}$
for
$i=1,\ldots , m$
. We also state analogous results for random products of
$2\times 2$
matrices, without any diophantine condition.
Flexibility of Lyapunov exponents with respect to two classes of measures on the torus
Authors: ERCHENKO ALENA
Published: May 2021

We consider a smooth area-preserving Anosov diffeomorphism
$f\colon \mathbb T^2\rightarrow \mathbb T^2$
homotopic to an Anosov automorphism L of
$\mathbb T^2$
. It is known that the positive Lyapunov exponent of f with respect to the normalized Lebesgue measure is less than or equal to the topological entropy of L, which, in addition, is less than or equal to the Lyapunov exponent of f with respect to the probability measure of maximal entropy. Moreover, the equalities only occur simultaneously. We show that these are the only restrictions on these two dynamical invariants.
Inverse problems and rigidity questions in billiard dynamics
Authors: KALOSHIN VADIM , SORRENTINO ALFONSO
Published: May 2021

A Birkhoff billiard is a system describing the inertial motion of a point mass inside a strictly convex planar domain, with elastic reflections at the boundary. The study of the associated dynamics is profoundly intertwined with the geometric properties of the domain: while it is evident how the shape determines the dynamics, a more subtle and difficult question is the extent to which the knowledge of the dynamics allows one to reconstruct the shape of the domain. This translates into many intriguing inverse problems and unanswered rigidity questions, which have been the focus of very active research in recent decades. In this paper we describe some of these questions, along with their connection to other problems in analysis and geometry, with particular emphasis on recent results obtained by the authors and their collaborators.
Changes in the nutritional content of children's lunches after the Food Dudes healthy eating programme
Authors: Marcano-Olivier Mariel , Sallaway-Costello Jake , McWilliams Lorna , Horne Pauline J. , Viktor Simon , Erjavec Mihela
Published: May 2021

Previous research into the effectiveness of healthy eating programmes has shown increases in healthful eating behaviour in primary schools; however, data collection methods have not been sufficiently sensitive to detect micronutrient changes. The present study extends the literature by measuring individual children's intake of macro- and micronutrients at lunchtime, before and after a programme targeting children's consumption of fruit and vegetables, to identify evidence-based health benefits of programme participation. Baseline data were collected over 4 d at lunchtime in two primary schools. The Food Dudes programme was then implemented in the intervention school. Follow-up data were collected over 4 d in each school 2 months after baseline. We employed a validated and sensitive photographic method to estimate individual children's (N 112) consumption of fruit, vegetables, and their intake of calories, macro- and selected micronutrients. Significant changes were observed in the intervention school but not in the control school: Children's consumption of fruit, vegetables, vitamin C and E intake increased, while their total energy consumption, fat, saturated fat, and sodium intake decreased. The present results show that the Food Dudes programme produced a positive nutritional change, with implications for its application as a healthy eating and obesity prevention intervention. These optimistic conclusions should be tested by further research to establish the longevity of the positive effects presented here.
Assurance monitoring of learning-enabled cyber-physical systems using inductive conformal prediction based on distance learning
Authors: Boursinos Dimitrios , Koutsoukos Xenofon
Published: May 2021

Machine learning components such as deep neural networks are used extensively in cyber-physical systems (CPS). However, such components may introduce new types of hazards that can have disastrous consequences and need to be addressed for engineering trustworthy systems. Although deep neural networks offer advanced capabilities, they must be complemented by engineering methods and practices that allow effective integration in CPS. In this paper, we proposed an approach for assurance monitoring of learning-enabled CPS based on the conformal prediction framework. In order to allow real-time assurance monitoring, the approach employs distance learning to transform high-dimensional inputs into lower size embedding representations. By leveraging conformal prediction, the approach provides well-calibrated confidence and ensures a bounded small error rate while limiting the number of inputs for which an accurate prediction cannot be made. We demonstrate the approach using three datasets of mobile robot following a wall, speaker recognition, and traffic sign recognition. The experimental results demonstrate that the error rates are well-calibrated while the number of alarms is very small. Furthermore, the method is computationally efficient and allows real-time assurance monitoring of CPS.
Surgical repair of discontinuous right pulmonary artery utilising an autologous main pulmonary artery flap: a case report and literature review
Authors: El Sherif Nibras , Cetta Frank , Stephens Elizabeth H.
Published: May 2021

This is a case of an infant with unilateral discontinuous right pulmonary artery. Cardiac catheterisation with pulmonary wedge injection diagnosed the anomaly and aided in surgical planning. The patient underwent semi-autologous surgical repair utilising an autologous main pulmonary artery flap. One month following discharge, he underwent successful balloon dilation of the residual stenosis and was discharged the same day.
Screening of polymorphic microsatellite markers from the whole-genome sequences of nipa (Nypa fruticans Wurmb.)
Authors: Mantiquilla Junaldo A. , Elumba Merlene E. , Shiao Meng-Shin , Chiang Yu-Chung
Published: May 2021

Nipa (Nypa fruticans Wurmb.), aside from being part of the mangrove forest ecosystem that has been under assault at an alarming rate, lacks information on its genetic variation at the population level for conservation planning purposes. Microsatellites, or simple sequence repeats (SSRs), are molecular markers employed to detect genetic variations in population studies. Here, the primers for this palm were identified through whole-genome sequencing using the Illumina® Sequencing Technology platform. Over half (52.4%) of SSRs consisted of mononucleotide repeats, whereas the remainder mostly consisted of dinucleotide (22.7%) and trinucleotide (22.4%) repeats. The frequencies of longer repeats (tetranucleotides, pentanucleotides and hexanucleotides) were exceptionally rare (2.5%). At least 18 out of 75 genomic loci were polymorphic, based on 37 randomly selected samples assayed for screening. Polymorphic loci (P) reached a mean of 72% across the Indo-West Pacific region. Estimates of genetic diversity showed a lower mean observed heterozygosity (Ho) (0.195) than expected (He) (0.316), suggesting evolutionary forces were acting across nipa populations. The fixation (F) index (0.388) supported this result, which indicates considerable genetic differentiation among populations in the region. An average of 2.111 alleles (Na) was obtained. In conclusion, these microsatellite markers are promising tools for genetic evaluation of nipa populations to facilitate characterization of this species in its distribution range.
Fragile Heterosexuality
Authors: West Keon , Borras-Guevara Martha Lucia , Morton Thomas , Greenland Katy
Published: May 2021

Abstract. Previous research demonstrates that membership of majority groups is often perceived as more fragile than membership of minority groups. Four studies ( N1 = 90, N2 = 247, N3 = 500, N4 = 1,176) investigated whether this was the case for heterosexual identity, relative to gay identity. Support for fragile heterosexuality was found using various methods: sexual orientation perceptions of a target who engaged in incongruent behavior, free-responses concerning behaviors required to change someone’s mind about a target’s sexual orientation, agreement with statements about men/women’s sexual orientation, and agreement with gender-neutral statements about sexual orientation. Neither participant nor target gender eliminated or reversed this effect. Additionally, we investigated multiple explanations (moderators) of the perceived difference in fragility between heterosexual identity and gay identity and found that higher estimates of the gay/lesbian population decreased the difference between the (higher) perceived fragility of heterosexual identity and the (lower) perceived fragility of gay identity.
Comparison of Surface Subsidence Measured by Airborne and Satellite InSAR Over Permafrost Areas Near Yellowknife Canada
Authors: Xu Xingyu , Liu Lin , Schaefer Kevin , Michaelides Roger
Published: May 2021

In addition to spaceborne Interferometric Synthetic Aperture Radar (InSAR), airborne data such as those obtained by the Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) have also been utilized to measure surface subsidence in permafrost areas in recent years. Motivated by the integration of multiplatform InSAR data, we generated two UAVSAR interferograms and one Advanced Land Observing Satellite (ALOS)‐2 L‐band interferogram over a permafrost area near Yellowknife, Canada, then compared the surface subsidence in the thaw seasons of 2017. The correlation coefficient and the root mean square error (RMSE) of subsidence difference are calculated to compare the airborne and spaceborne InSAR measurements. The results demonstrate that the two UAVSAR measurements are self‐consistent, with the correlation coefficient between independent airborne measurements ∼0.7. While the RMSE of the difference between surface subsidence measured by UAVSAR and ALOS2 is ∼2.0 cm, and the correlation coefficients are less than 0.41, that is, a noticeable deviation exists between the UAVSAR and ALOS2 results possibly due to different spatial resolution and the calibration processing of airborne and spaceborne InSAR data. In addition, both UAVSAR and ALOS2 interferograms show larger surface subsidence within taiga needleleaf forest regions than in regions of other biome types (including needleleaf forest, shrubland, and grassland). The results demonstrate that a scheme for the elimination of systematic differences needs to be developed before merging multisource InSAR results. This intercomparison will provide valuable insights for narrowing the gap between radar‐based measurements and planning the integration of airborne and satellite InSAR measurements in permafrost environments.
Uplift and Exposure of Serpentinized Massifs: Modeling Differential Serpentinite Diapirism and Exhumation of the Troodos Mantle Sequence, Cyprus
Authors: Evans Aled D. , Teagle Damon A. H. , Craw Dave , Henstock Timothy J. , Falcon‐Suarez Ismael Himar
Published: May 2021

Serpentinized mantle peridotites form prominent mountains, including the highest elevations of the Troodos ophiolite in Cyprus (Mount Olympus, 1,952 m), but to date, only qualitative mechanisms have been proposed to explain the uplift of mantle rocks to high altitudes. Serpentinization reactions between mantle rocks and water result in profound changes to the rheology and physical properties of peridotites including significant density reduction (∼900 kg/m3). Field observations, density measurements, and isostatic uplift and erosional modeling provide new constraints on the contribution of serpentinization to the uplift of the Troodos Mantle Sequence. Different serpentinization styles have resulted in two distinct serpentinite domains with contrasting densities. Our modeling shows that the Troodos Mountains can form within the geologically constrained uplift time frame (∼5.5 Myr) exclusively through partial serpentinization reactions. We interpret the serpentinite domains as two nested diapirs that formed due to different extents of serpentinization and density reduction. Differential uplift and exhumation have decoupled the two serpentinite diapirs from the originally overlying ocean crustal rocks. Once at high altitudes the incursion of meteoric water reinforced coupled deformation‐alteration‐recrystallization processes in the shallow subsurface producing a localized low density completely serpentinized diapir. A second decoupling between the contrasting serpentinite diapirs results in localized differential uplift and exhumation, extruding deep materials to the east of Mount Olympus. Application of our modeling to other serpentinite massifs (e.g., St. Peter and St. Paul Rocks, New Idria, California) highlights the contribution of isostasy to the uplift of serpentinized massifs.
A Summary of National Oceanic and Atmospheric Administration Space Weather Prediction Center Proton Event Forecast Performance and Skill
Authors: Bain H. M. , Steenburgh R. A. , Onsager T. G. , Stitely E. M.
Published: May 2021

The effects of solar radiation storms at Earth are felt across a number of technology‐based industries. Energetic particles present during these storms impact electrical components on spacecraft, disrupt high frequency radio communications, and pose a radiation risk for passengers and crew on polar flight routes, as well as for astronauts. An essential aspect of space weather forecasting is therefore to predict the occurrence and properties of a solar proton event before it occurs. In this study, we review radiation storm products issued by the National Oceanic and Atmospheric Administration's Space Weather Prediction Center (SWPC) during Solar Cycles 23 and 24. These include three‐day probabilistic proton event forecasts and short‐term Warning and Alert hazard products. We present performance metrics and forecast skill scores for SWPC probabilistic forecasts and Warning products, which can be used as a benchmark for assessing the performance of radiation storm forecast models.
Characterization of the Candidate Landing Region for Tianwen‐1—China's First Mission to Mars
Authors: Wu Bo , Dong Jie , Wang Yiran , Li Zhaojin , Chen Zeyu , Liu Wai Chung , Zhu Jiaming , Chen Long , Li Yuan , Rao Wei
Published: May 2021

This paper presents our efforts to characterize the candidate landing region (109°–133°E, 23°–30°N) for Tianwen‐1, China's first mission to Mars, in terms of engineering safety and scientific significance. Topographic analysis reveals that the region has a low elevation around −4,230 m, and 98% of the region have slopes smaller than 8°. The geomorphological mapping and analysis show that the region has an average crater density of about 28 craters (≥200 m in diameter) per 100 square kilometers, with several clusters of high crater densities distributed around the center of the region. There are also pitted cones distributed mainly in the southern part of the region, with a density of approximately 6.6 cones per 100 square kilometers in specific local areas. The region has rock abundances ranging from 1% to 23%, with local clusters of low and high rock abundances. The region comprises four main geological units, including a lowland unit formed in the Late Hesperian and a volcanic unit formed in the Amazonian and Hesperian period. Their specific surface ages are estimated through the analysis of crater size‐frequency distribution. Combining the engineering constraints on surface slopes, crater density, cone density, and rock abundance, a hazard map of the candidate landing region is generated for landing site evaluation and safety assessment. Based on the results, we further discuss the potential scientific outcomes from the exploration in this region. The findings will be helpful for the mission planning and maximization of the scientific return from Tianwen‐1, and complement existing Martian scientific research.
Re‐Reconnection Processes of Magnetopause Flux Ropes: Three‐Dimensional Global Hybrid Simulations
Authors: Guo Jin , Lu San , Lu Quanming , Lin Yu , Wang Xueyi , Huang Kai , Wang Rongsheng , Wang Shui
Published: May 2021

Magnetopause flux ropes (FRs) play a crucial role in the transport of energy and plasma from the solar wind to the Earth’s magnetosphere. Once formed by multiple X‐line reconnection, the FRs move poleward, during which they can coalesce with each other through a re‐reconnection process. The poleward moving FRs eventually coalesce into the cusp regions, through another re‐reconnection process. In this paper, using three‐dimensional (3‐D) global hybrid simulations, we study the two re‐reconnection processes of magnetopause FRs by examining the topological changes of magnetic field lines. These re‐reconnection processes are essentially 3‐D. Two FRs coalesce with each other and form two new FRs (instead of one new FR in the two‐dimensional regime). When FRs move close to the cusp region, their field lines can reconnect with the cusp field lines so that the FRs can break into two shorter ones. The two re‐reconnection processes increase the plasma energy and the magnetic flux connected to the Earth, which favors particle and energy transport toward the Earth’s magnetosphere.
On the Sources and Sizes of Uncertainty in Predicting the Arrival Time of Interplanetary Coronal Mass Ejections Using Global MHD Models
Authors: Riley Pete , Ben‐Nun Michal
Published: May 2021

Accurate predictions of the properties of interplanetary coronal mass ejection (ICME)‐driven disturbances are a key objective for space weather forecasts. The ICME's time of arrival (ToA) at Earth is an important parameter, and one that is amenable to a variety of modeling approaches. Previous studies suggest that the best models can predict the arrival time to within an absolute uncertainty of 10–15 h. Here, we investigate the main sources of uncertainty in predicting a CME's ToA at Earth. These can be broken into two main categories: (a) the initial properties of the ejecta, including its speed, mass, and direction of propagation and (b) the properties of the ambient solar wind into which it propagates. To estimate the relative contribution to ToA uncertainties, we construct a set of numerical experiments of cone‐model CMEs, where we vary the initial speed, mass, and direction at the inner radial boundary. Additionally, we build an ensemble of 12 ambient solar wind solutions using realizations from the ADAPT model. We find that each component in the chain contributes between ±2.5 and ±7 h of uncertainty to the estimate of the CME's ToA. Importantly, different realizations of the synoptic produce the largest uncertainties. This suggests that estimates of ToA will continue to be plagued with intrinsic uncertainties of ±10 h until tighter constraints can be found for these boundary conditions. Our results suggest that there are clear benefits to focused investigations aimed at reducing the uncertainties in CME speed, mass, direction, and input boundary magnetic fields.
Coherent interaction of atoms with a beam of light confined in a light cage
Authors: Davidson-Marquis Flavie , Gargiulo Julian , Gómez-López Esteban , Jang Bumjoon , Kroh Tim , Müller Chris , Ziegler Mario , Maier Stefan A. , Kübler Harald , Schmidt Markus A. , Benson Oliver
Published: May 2021

Controlling coherent interaction between optical fields and quantum systems in scalable, integrated platforms is essential for quantum technologies. Miniaturised, warm alkali-vapour cells integrated with on-chip photonic devices represent an attractive system, in particular for delay or storage of a single-photon quantum state. Hollow-core fibres or planar waveguides are widely used to confine light over long distances enhancing light-matter interaction in atomic-vapour cells. However, they suffer from inefficient filling times, enhanced dephasing for atoms near the surfaces, and limited light-matter overlap. We report here on the observation of modified electromagnetically induced transparency for a non-diffractive beam of light in an on-chip, laterally-accessible hollow-core light cage. Atomic layer deposition of an alumina nanofilm onto the light-cage structure was utilised to precisely tune the high-transmission spectral region of the light-cage mode to the operation wavelength of the atomic transition, while additionally protecting the polymer against the corrosive alkali vapour. The experiments show strong, coherent light-matter coupling over lengths substantially exceeding the Rayleigh range. Additionally, the stable non-degrading performance and extreme versatility of the light cage provide an excellent basis for a manifold of quantum-storage and quantum-nonlinear applications, highlighting it as a compelling candidate for all-on-chip, integrable, low-cost, vapour-based photon delay.
Antitumor effect of Melaleuca alternifolia essential oil and its main component terpinen-4-ol in combination with target therapy in melanoma models
Authors: Di Martile Marta , Garzoli Stefania , Sabatino Manuela , Valentini Elisabetta , D’Aguanno Simona , Ragno Rino , Del Bufalo Donatella
Published: May 2021

Essential oils (EOs) have been recently emerging for their promising biological activities in preventing tumorigenesis or progression of different tumor histotypes, including melanoma. In this study, we investigated the antitumor activity of a panel of EOs in different tumor models. The ability of Melaleuca alternifolia (tea tree oil) and its main component, terpinen-4-ol, to sensitize the target therapy currently used for melanoma treatment was also assessed. Our results demonstrated that EOs differently affect the viability of human cancer cells and led us to select six EOs effective in melanoma and lung cancer cells, without toxic effects in human fibroblasts. When combined with dabrafenib and/or trametinib, Melaleuca alternifolia synergistically reduced the viability of melanoma cells by activating apoptosis. Through machine learning classification modeling, α-terpineol, tepinolene, and terpinen-4-ol, three components of Melaleuca alternifolia, were identified as the most likely relevant components responsible for the EO’s antitumor effect. Among them, terpinen-4-ol was recognized as the Melaleuca alternifolia component responsible for its antitumor and proapoptotic activity. Overall, our study holds promise for further analysis of EOs as new anticancer agents and supports the rationale for their use to improve target therapy response in melanoma.
Dysregulated immunity in PID patients with low GARP expression on Tregs due to mutations in LRRC32
Authors: Lehmkuhl Peter , Gentz Magdalena , Garcia de Otezya Andres Caballero , Grimbacher Bodo , Schulze-Koops Hendrik , Skapenko Alla
Published: May 2021

Immune dysregulation diseases are characterized by heterogeneous clinical manifestations and may have severe disease courses. The identification of the genetic causes of these diseases therefore has critical clinical implications. We performed whole-exome sequencing of patients with immune dysregulation disorders and identified two patients with previously undescribed mutations in LRRC32, which encodes glycoprotein A repetitions predominant (GARP). These patients were characterized by markedly reduced numbers and frequencies of regulatory T cells (Tregs). Tregs with mutated LRRC32 exhibited strongly diminished cell-surface GARP expression and reduced suppressor function. In a model of conditional Garp deficiency in mice, we confirmed increased susceptibility to inflammatory diseases once GARP expression on Tregs was decreased. Garp deficiency led to an unstable Treg phenotype due to diminished Foxp3 protein acetylation and stability. Our study reinforces the understanding of the immunological mechanisms of immune dysregulation and expands the knowledge on the immunological function of GARP as an important regulator of Treg stability.
Evidence accumulation relates to perceptual consciousness and monitoring
Authors: Pereira Michael , Megevand Pierre , Tan Mi Xue , Chang Wenwen , Wang Shuo , Rezai Ali , Seeck Margitta , Corniola Marco , Momjian Shahan , Bernasconi Fosco , Blanke Olaf , Faivre Nathan
Published: May 2021

A fundamental scientific question concerns the neural basis of perceptual consciousness and perceptual monitoring resulting from the processing of sensory events. Although recent studies identified neurons reflecting stimulus visibility, their functional role remains unknown. Here, we show that perceptual consciousness and monitoring involve evidence accumulation. We recorded single-neuron activity in a participant with a microelectrode in the posterior parietal cortex, while they detected vibrotactile stimuli around detection threshold and provided confidence estimates. We find that detected stimuli elicited neuronal responses resembling evidence accumulation during decision-making, irrespective of motor confounds or task demands. We generalize these findings in healthy volunteers using electroencephalography. Behavioral and neural responses are reproduced with a computational model considering a stimulus as detected if accumulated evidence reaches a bound, and confidence as the distance between maximal evidence and that bound. We conclude that gradual changes in neuronal dynamics during evidence accumulation relates to perceptual consciousness and perceptual monitoring in humans.
Investment incentive reduced by climate damages can be restored by optimal policy
Authors: Willner Sven N. , Glanemann Nicole , Levermann Anders
Published: May 2021

Increasing greenhouse gas emissions are likely to impact not only natural systems but economies worldwide. If these impacts alter future economic development, the financial losses will be significantly higher than the mere direct damages. So far, potentially aggravating investment responses were considered negligible. Here we consistently incorporate an empirically derived temperature-growth relation into the simple integrated assessment model DICE. In this framework we show that, if in the next eight decades varying temperatures impact economic growth as has been observed in the past three decades, income is reduced by ~ 20% compared to an economy unaffected by climate change. Hereof ~ 40% are losses due to growth effects of which ~ 50% result from reduced incentive to invest. This additional income loss arises from a reduced incentive for future investment in anticipation of a reduced return and not from an explicit climate protection policy. Under economically optimal climate-change mitigation, however, optimal investment would only be reduced marginally as mitigation efforts keep returns high.
Acetylation of PAX7 controls muscle stem cell self-renewal and differentiation potential in mice
Authors: Sincennes Marie-Claude , Brun Caroline E. , Lin Alexander Y. T. , Rosembert Tabitha , Datzkiw David , Saber John , Ming Hong , Kawabe Yoh-ichi , Rudnicki Michael A.
Published: May 2021

Muscle stem cell function has been suggested to be regulated by Acetyl-CoA and NAD+ availability, but the mechanisms remain unclear. Here we report the identification of two acetylation sites on PAX7 that positively regulate its transcriptional activity. Lack of PAX7 acetylation reduces DNA binding, specifically to the homeobox motif. The acetyltransferase MYST1 stimulated by Acetyl-CoA, and the deacetylase SIRT2 stimulated by NAD +, are identified as direct regulators of PAX7 acetylation and asymmetric division in muscle stem cells. Abolishing PAX7 acetylation in mice using CRISPR/Cas9 mutagenesis leads to an expansion of the satellite stem cell pool, reduced numbers of asymmetric stem cell divisions, and increased numbers of oxidative IIA myofibers. Gene expression analysis confirms that lack of PAX7 acetylation preferentially affects the expression of target genes regulated by homeodomain binding motifs. Therefore, PAX7 acetylation status regulates muscle stem cell function and differentiation potential to facilitate metabolic adaptation of muscle tissue.
Diverse electronic and magnetic properties of CrS2 enabling strain-controlled 2D lateral heterostructure spintronic devices
Authors: Chen Kaiyun , Deng Junkai , Yan Yuan , Shi Qian , Chang Tieyan , Ding Xiangdong , Sun Jun , Yang Sen , Liu Jefferson Zhe
Published: May 2021

Lateral heterostructures of two-dimensional (2D) materials, integrating different phases or materials into a single piece of nanosheet, have attracted intensive research interests for electronic devices. Extending the 2D lateral heterostructures to spintronics demands more diverse electromagnetic properties of 2D materials. In this paper, using density functional theory calculations, we survey all IV, V, and VI group transition metal dichalcogenides (TMDs) and discover that CrS2 has the most diverse electronic and magnetic properties: antiferromagnetic (AFM) metallic 1T phase, non-magnetic (NM) semiconductor 2H phase, and ferromagnetic (FM) semiconductor 1T′ phase with a Curie temperature of ~1000 K. Interestingly, we find that a tensile or compressive strain can turn the 1T′ phase into a spin-up or spin-down half-metal. Such strain tunability can be attributed to the lattice deformation under tensile/compressive strain that selectively promotes the spin-up/spin-down VBM (valence band bottom) orbital interactions. The diverse electromagnetic properties and the strain tunability enable strain-controlled spintronic devices using a single piece of CrS2 nanosheet with improved energy efficiency. As a demo, a prototypical design of the spin-valve logic device is presented. It offers a promising solution to address the challenge of high energy consumption in miniaturized spintronic devices.
Crystal-chirality-dependent control of magnetic domains in a time-reversal-broken antiferromagnet
Authors: Kimura Kenta , Kato Yasuyuki , Kimura Shojiro , Motome Yukitoshi , Kimura Tsuyoshi
Published: May 2021

Chiral-lattice magnets can exhibit a variety of physical phenomena when time-reversal symmetry is broken by their magnetism. For example, nonreciprocal responses of (quasi)particles have been widely observed in chiral-lattice magnets with macroscopic magnetization. Meanwhile, time-reversal symmetry can also be broken in antiferromagnets without magnetization. Here we report an unconventional chirality-magnetism coupling in a chiral-lattice antiferromagnet Pb(TiO)Cu4(PO4)4 whose time-reversal symmetry is broken by an ordering of magnetic quadrupoles. Our experiments demonstrate that a sign of magnetic quadrupoles is controllable by a magnetic field only, which is generally impossible in consideration of the symmetry of magnetic quadrupoles. Furthermore, we find that the sign of magnetic quadrupoles stabilized by applying a magnetic field is reversed by a switching of the chirality. Our theoretical calculations and phenomenological approach reveal that this unusual coupling between the chirality and magnetic quadrupoles is mediated by the previously-unrecognized magnetic octupoles that emerge due to the chirality.
Prostate cancer risk variants of the HOXB genetic locus
Authors: Dupont William D. , Breyer Joan P. , Johnson Spenser H. , Plummer W. Dale , Smith Jeffrey R.
Published: May 2021

The G84E germline mutation of HOXB13 predisposes to prostate cancer and is clinically tested for familial cancer care. We investigated the HOXB locus to define a potentially broader contribution to prostate cancer heritability. We sought HOXB locus germline variants altering prostate cancer risk in three European-ancestry case–control study populations (combined 7812 cases and 5047 controls): the International Consortium for Prostate Cancer Genetics Study; the Nashville Familial Prostate Cancer Study; and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Multiple rare genetic variants had concordant and strong risk effects in these study populations and exceeded genome-wide significance. Independent risk signals were best detected by sentinel variants rs559612720 within SKAP1 (OR = 8.1, P = 2E−9) and rs138213197 (G84E) within HOXB13 (OR = 5.6, P = 2E−11), separated by 567 kb. Half of carriers inherited both risk alleles, while others inherited either alone. Under mutual adjustment, the variants separately carried 3.6- and 3.1-fold risk, respectively, while joint inheritance carried 11.3-fold risk. These risks were further accentuated among men meeting criteria for hereditary prostate cancer, and further still for those with early-onset or aggressive disease. Among hereditary prostate cancer cases diagnosed under age 60 and with aggressive disease, joint inheritance carried a risk of OR = 27.7 relative to controls, P = 2E−8. The HOXB sentinel variant pair more fully captured genetic risk for prostate cancer within the study populations than either variant alone.
High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells
Authors: Topel Hande , Bağırsakçı Ezgi , Yılmaz Yeliz , Güneş Ayşim , Bağcı Gülsün , Çömez Dehan , Kahraman Erkan , Korhan Peyda , Atabey Neşe
Published: May 2021

Hepatocellular carcinoma (HCC) is strongly associated with metabolic dysregulations/deregulations and hyperglycemia is a common metabolic disturbance in metabolic diseases. Hyperglycemia is defined to promote epithelial to mesenchymal transition (EMT) of cancer cells in various cancers but its molecular contribution to HCC progression and aggressiveness is relatively unclear. In this study, we analyzed the molecular mechanisms behind the hyperglycemia-induced EMT in HCC cell lines. Here, we report that high glucose promotes EMT through activating c-Met receptor tyrosine kinase via promoting its ligand-independent homodimerization. c-Met activation is critical for high glucose induced acquisition of mesenchymal phenotype, survival under high glucose stress and reprogramming of cellular metabolism by modulating glucose metabolism gene expression to promote aggressiveness in HCC cells. The crucial role of c-Met in high glucose induced EMT and aggressiveness may be the potential link between metabolic syndrome-related hepatocarcinogenesis and/or HCC progression. Considering c-Met inhibition in hyperglycemic patients would be an important complementary strategy for therapy that favors sensitization of HCC cells to therapeutics.
Novel semi-automated fluorescence microscope imaging algorithm for monitoring IgG aggregates in serum
Authors: Sreenivasan Shravan , Sonawat Deepak , Mandal Shyamapada , Khare Kedar , Rathore Anurag S.
Published: May 2021

Analysis of therapeutic IgG aggregates in serum is a potential area of investigation as it can give deeper insights about the function, immunogenic issues and protein interaction associated with the aggregates. To overcome various complexities associated with the existing analytical techniques for analyzing aggregates in serum, a novel florescence microscopy-based image processing approach was developed. The monoclonal antibody (mAb) was tagged with a fluorescent dye, fluorescein isothiocyanate (FITC). Aggregates, generated by stirring, were spiked into serum and images were captured at various time points. After denoising, thresholding by weighted median, 1D Otsu, and 2D Otsu was attempted and a modified 2D Otsu, a new mode of thresholding, was developed. This thresholding method was found to be highly effective in removing noises and retaining analyte sizes. Out of 0–255, the optimized threshold value obtained for the images discussed in modified 2D Otsu was 9 while 2D Otsu’s overestimated values were 38 and 48. Other morphological operations were applied after thresholding and the area, perimeter, circularity, and radii of the aggregates in these images were calculated. The proposed algorithm offers an approach for analysis of aggregates in serum that is simpler to implement and is complementary to existing approaches.
Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP
Authors: Steel Ryan W. J. , Vigdorovich Vladimir , Dambrauskas Nicholas , Wilder Brandon K. , Arredondo Silvia A. , Goswami Debashree , Kumar Sudhir , Carbonetti Sara , Swearingen Kristian E. , Nguyen Thao , Betz Will , Camargo Nelly , Fisher Bridget S. , Soden Jo , Thomas Helen , Freeth Jim , Moritz Robert L. , Noah Sather D. , Kappe Stefan H. I.
Published: May 2021

Following their inoculation by the bite of an infected Anopheles mosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors. Here, we identified the human platelet-derived growth factor receptor β (hPDGFRβ) as one such protein receptor. Deletion constructs showed that the von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells. We also demonstrate that this interaction is conserved in the human-infective parasite Plasmodium vivax, but not the rodent-infective parasite Plasmodium yoelii. We observed expression of hPDGFRβ mainly in cells associated with the vasculature suggesting that TRAP:hPDGFRβ interaction may play a role in the recognition of blood vessels by invading sporozoites.
Longitudinal effects of meditation on brain resting-state functional connectivity
Authors: Zhang Zongpai , Luh Wen-Ming , Duan Wenna , Zhou Grace D. , Weinschenk George , Anderson Adam K. , Dai Weiying
Published: May 2021

Changes in brain resting-state functional connectivity (rsFC) were investigated using a longitudinal design by following a 2-month focused attention meditation (FAM) practice and analyzing their association with FAM practice time. Ten novice meditators were recruited from a university meditation course. Participants were scanned with a resting-state fMRI sequence with multi-echo EPI acquisition at baseline and at the 2-month follow-up. Total FAM practice time was calculated from the daily log of the participants. We observed significantly increased rsFC between the posterior cingulate cortex (PCC) and dorsal attention network (DAN), the right middle temporal (RMT) region and default mode network (DMN), the left and right superior parietal lobules (LSPL/RSPL) and DMN, and the LSPL/RSPL and DAN. Furthermore, the rsFC between the LSPL and medial prefrontal cortex was significantly associated with the FAM practice time. These results demonstrate increased connectivity within the DAN, between the DMN and DAN, and between the DMN and visual cortex. These findings demonstrate that FAM can enhance the brain connection among and within brain networks, especially DMN and DAN, indicating potential effect of FAM on fast switching between mind wandering and focused attention and maintaining attention once in the attentive state.
C1q/TNF-related protein-9 ameliorates hypoxia-induced pulmonary hypertension by regulating secretion of endothelin-1 and nitric oxide mediated by AMPK in rats
Authors: Jin Qiaoyan , Su Hui , Yang Rui , Tan Yanzhen , Li Buying , Yi Wei , Dong Qianqian , Zhang Haifeng , Xing Wenjuan , Sun Xin
Published: May 2021

Injury/dysfunction of the endothelium of pulmonary arteries contributes to hypoxia-induced pulmonary hypertension (HPH). We investigated whether C1q/tumor necrosis factor-related protein-9 (CTRP9), a newly identified cardiovascular agent, has protective roles in the development of HPH. HPH was induced in adult male rats by chronic hypobaric hypoxia. CTRP9 overexpression by adeno-associated virus (AAV)-CTRP9 transfection attenuated the increases in right ventricular systolic pressure, right ventricular hypertrophy index, and pulmonary arterial remodeling of rats under hypoxia. Importantly, CTRP9 overexpression improved endothelium-dependent vasodilation in pulmonary arterioles in HPH rats. CTRP9 overexpression enhanced expression of phosphorylated 5′-adenosine monophosphate-activated protein kinase (p-AMPK) and phosphorylated endothelial nitric oxide synthase (p-eNOS), and reduced phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) expression in pulmonary microvascular endothelial cells (PMVECs) of HPH rats. In cultured PMVECs, CTRP9 not only preserved the decrease of AMPK and eNOS phosphorylation level and nitric oxide (NO) production induced by hypoxia, but also blocked the increase in hypoxia-induced ERK1/2 phosphorylation level and endothelin (ET)-1 production. Furthermore, the effects of CTRP9 were interrupted by inhibitors or knockdown of AMPK. CTRP9 enhances NO production and reduces ET-1 production by regulating AMPK activation. CTRP9 could be a target for HPH.
Neutrophil to lymphocyte ratio and fibrinogen values in predicting patients with type B aortic dissection
Authors: Li Shuangshuang , Yang Jin , Dong Jian , Guo Renle , Chang Sheng , Zhu Hongqiao , Li Zhaohui , Zhou Jian , Jing Zaiping
Published: May 2021

The aim of this study is to detect the diagnosis value of neutrophil lymphocyte ratio (NLR) and fibrinogen (FIB) in type B aortic dissection (TBAD) patients. This retrospective observation study consisted patients with TBAD, aortic aneurysm and physical examination between January 1, 2016 and December 31, 2019. Demographic and clinical information after the first admission were collected. Multivariate logistic regression analysis was performed to explore the correlational relationship between NLR, FIB and TBAD. Receiver Operating Characteristic Curve (ROC) was performed to evaluate the diagnostic implication of NLR and FIB in TBAD patients. Six hundred and six patients who were first diagnosed with TBAD were included. Control groups were 202 aortic aneurysm and 140 physical examination subjects. The level of NLR and FIB in aortic dissection patients was significantly higher than aortic aneurysm patients and healthy group (P < 0.001). According to the results of multivariate logistic regression analysis, NLR and FIB were independent risk factors of aortic dissection, and the odds ratio (OR) and 95% confidence interval (CI) value of NLR and FIB were 1.499 (1.126–1.738) and 1.914 (1.475–2.485), respectively. The area under the curve (AUC) was 0.836 of NLR and 0.756 of FIB. NLR and FIB showed high specificity, 89% and 83% respectively. This is the first study provided information on the diagnosis performance of NLR and FIB in TBAD patients. NLR and FIB showed high specificity, which may be a valuable tool for the diagnosis of TBAD.