bluuebunny/crossref_metadata_2025 huggingface dataset:
Physics‐constrained non‐Gaussian probabilistic learning on manifolds
Authors: Soize Christian , Ghanem Roger
Published: August 2019

An extension of the probabilistic learning on manifolds (PLoM), recently introduced by the authors, has been presented: In addition to the initial data set given for performing the probabilistic learning, constraints are given, which correspond to statistics of experiments or of physical models. We consider a non‐Gaussian random vector whose unknown probability distribution has to satisfy constraints. The method consists in constructing a generator using the PLoM and the classical Kullback‐Leibler minimum cross‐entropy principle. The resulting optimization problem is reformulated using Lagrange multipliers associated with the constraints. The optimal solution of the Lagrange multipliers is computed using an efficient iterative algorithm. At each iteration, the Markov chain Monte Carlo algorithm developed for the PLoM is used, consisting in solving an Itô stochastic differential equation that is projected on a diffusion‐maps basis. The method and the algorithm are efficient and allow the construction of probabilistic models for high‐dimensional problems from small initial data sets and for which an arbitrary number of constraints are specified. The first application is sufficiently simple in order to be easily reproduced. The second one is relative to a stochastic elliptic boundary value problem in high dimension.
Synthesis of cyclic poly(l‐lactide) catalyzed by Bismuth Salicylates—A combination of two drugs
Authors: Kricheldorf Hans R. , Weidner Steffen M. , Scheliga Felix
Published: August 2019

l‐lactide was polymerized in bulk at 160 or 180°C with mixtures of bismuth subsalicylate (BiSub) and salicylic (SA) as catalysts. The SA/Bi ratio and the monomer/Bi ratio were varied. The highest molecular weights (weight average, Mw) were achieved at a SA/Bi ratio of 1/1 (Mw up to 92 000 g mol−1). l‐Lactide was also polymerized with combinations of BiSub and silylated SA, and Mw values up to 120 000 g mol−1 were achieved at 180°C. MALDI‐TOF mass spectrometry and Mark‐Houwink‐Sakurada measurements proved that under optimized reaction conditions the resulting polylactides consist of cycles. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 2056–2063
TWIST2: A new candidate tumor suppressor in prostate cancer
Authors: Zhao Chengxiao , Zhang Wei , Zhu Xiaoquan , Xu Yong , Yang Kuo , Wei Dong , Liang Siying , Zhao Fan , Zhang Yaoguang , Chen Xin , Sun Liang , Yuan Huiping , Shi Xiaohong , Wang Xin , Liu Ming , Yang Fan , Wang Jianye , Yang Ze
Published: August 2019

Background

Prostate cancer (PCa) is a leading cause of cancer morbidity and mortality in men worldwide; however, PCa incidence and mortality rates vary widely across geographic regions and ethnic groups. The current study was designed to elucidate the pivotal factors involved in PCa occurrence and development.

Methods

We performed RNA sequencing on the prostate tumor and adjacent normal tissues from Chinese PCa patients. Genes identified via genome‐wide expression profile analysis were validated by quantitative reverse‐transcription polymerase chain reaction and immunohistochemistry. Hypermethylation of CpG islands was assessed by nested methylation‐specific PCR. Whole genome microarray analysis was performed using an Affymetrix GeneChip.

Results

We identified nine possible abnormally expressed genes (P < .05) and then revealed TWIST2 as having strikingly lower expression in tumors than in control tissues (P < .01). Low messenger RNA expression levels of TWIST2 were associated with hypermethylation of CpG islands in its promoter region. In accordance with these findings, PCa tumor tissues showed markedly decreased TWIST2 protein expression compared to that in both normal and prostatic intraepithelial neoplasia tissues by immunohistochemical staining. Ectopic expression of TWIST2 in LNCap cells not only inhibited cell proliferation and colony formation in vitro and tumor growth in vivo but also induced transcriptional repression of a cell proliferation‐related gene cohort, including androgen receptor signaling mediators, cyclins, homeobox genes, forkhead box genes, and SOX2.

Conclusions

Our results suggest that TWIST2 could function as a tumor suppressor involved in the pathogenesis of PCa by influencing the expression of target genes and that hypermethylation of the TWIST2 promoter in prostate tumors may be an underlying mechanism for TWIST2 transcriptional silencing.
Semimechanistic Pharmacodynamic Modeling of Aztreonam‐Avibactam Combination to Understand Its Antimicrobial Activity Against Multidrug‐Resistant Gram‐Negative Bacteria
Authors: Chauzy Alexia , Gaelzer Silva Torres Bruna , Buyck Julien , de Jonge Boudewijn , Adier Christophe , Marchand Sandrine , Couet William , Grégoire Nicolas
Published: August 2019

Aztreonam‐avibactam (ATM‐AVI) is a promising combination to treat serious infections caused by multidrug‐resistant (MDR) pathogens. Three distinct mechanisms of action have been previously characterized for AVI: inhibition of ATM degradation by β‐lactamases, proper bactericidal effect, and enhancement of ATM bactericidal activity. The aim of this study was to quantify the individual contribution of each of the three AVI effects. In vitro static time‐kill studies were performed on four MDR Enterobacteriaceae with different β‐lactamase profiles. β‐Lactamase activity was characterized by measuring ATM concentrations over 27 hours. Data were analyzed by a semimechanistic pharmacodynamics modeling approach. Surprisingly, even though AVI prevented ATM degradation, the combined bactericidal activity was mostly explained by the enhancement of ATM effect within clinical range of ATM (5–125 mg/L) and AVI concentrations (0.9–22.5 mg/L). Therefore, when selecting a β‐lactamase inhibitor for combination with a β‐lactam, its capability to enhance the β‐lactam activity should be considered in addition to the spectrum of β‐lactamases inhibited.
Expanded Physiologically‐Based Pharmacokinetic Model of Rifampicin for Predicting Interactions With Drugs and an Endogenous Biomarker via Complex Mechanisms Including Organic Anion Transporting Polypeptide 1B Induction
Authors: Asaumi Ryuta , Menzel Karsten , Lee Wooin , Nunoya Ken‐ichi , Imawaka Haruo , Kusuhara Hiroyuki , Sugiyama Yuichi
Published: August 2019

As rifampicin can cause the induction and inhibition of multiple metabolizing enzymes and transporters, it has been challenging to accurately predict the complex drug–drug interactions (DDIs). We previously constructed a physiologically‐based pharmacokinetic (PBPK) model of rifampicin accounting for the components for the induction of cytochrome P450 (CYP) 3A/CYP2C9 and the inhibition of organic anion transporting polypeptide 1B (OATP1B). This study aimed to expand and verify the PBPK model for rifampicin by incorporating additional components for the induction of OATP1B and CYP2C8 and the inhibition of multidrug resistance protein 2. The established PBPK model was capable of accurately predicting complex rifampicin‐induced alterations in the profiles of glibenclamide, repaglinide, and coproporphyrin I (an endogenous biomarker of OATP1B activities) with various dosing regimens. Our comprehensive rifampicin PBPK model may enable quantitative prediction of DDIs across diverse potential victim drugs and endogenous biomarkers handled by multiple metabolizing enzymes and transporters.
Physiologically‐Based Pharmacokinetic Modeling Approach to Predict Rifampin‐Mediated Intestinal P‐Glycoprotein Induction
Authors: Yamazaki Shinji , Costales Chester , Lazzaro Sarah , Eatemadpour Soraya , Kimoto Emi , Varma Manthena V.
Published: August 2019

Physiologically‐based pharmacokinetic (PBPK) modeling is a powerful tool to quantitatively describe drug disposition profiles in vivo, thereby providing an alternative to predict drug–drug interactions (DDIs) that have not been tested clinically. This study aimed to predict effects of rifampin‐mediated intestinal P‐glycoprotein (Pgp) induction on pharmacokinetics of Pgp substrates via PBPK modeling. First, we selected four Pgp substrates (digoxin, talinolol, quinidine, and dabigatran etexilate) to derive in vitro to in vivo scaling factors for intestinal Pgp kinetics. Assuming unbound Michaelis‐Menten constant (Km) to be intrinsic, we focused on the scaling factors for maximal efflux rate (Jmax) to adequately recover clinically observed results. Next, we predicted rifampin‐mediated fold increases in intestinal Pgp abundances to reasonably recover clinically observed DDI results. The modeling results suggested that threefold to fourfold increases in intestinal Pgp abundances could sufficiently reproduce the DDI results of these Pgp substrates with rifampin. Hence, the obtained fold increases can potentially be applicable to DDI prediction with other Pgp substrates.
Sustainability
Authors: Chang Chein‐Chi , DiGiovanni Kimberly , Mei Ying
Published: August 2019

This review on Sustainability covers selected 2018 publications on the focus of sustainability. It is divided into the following sections: (a) Water quantity; (b) Water quality; (c) Climate change and resilience; (d) Planning and ecosystem evaluation; (e) Life cycle assessment (LCA) applications; (f) Sustainable management; (g) Sustainability and asset management; (h) Sustainability in wastewater treatment; (i) Sustainable water and wastewater utilities; (j) Sustainable water resource management.
Bioenergy from biofuel residues and waste
Authors: Plante Luke , Sheehan Nathaniel P. , Bier Peter , Murray Kyle , Quell Kimberly , Ouellette Charles , Martinez Erick
Published: August 2019

This section presents a review of the scientific literature published in 2018 on topics relating to sustainable bioenergy from biofuel residues and waste. This review is divided into the following sections: Feedstocks, Bioethanol, Biodiesel, Biohydrogen, Hydrogen, Biofuel Residues, Microalgae, and Lignocelluloses.
Bigger or Better? Research-Based Reflections on the Cultural Deconstruction of Rural Schools in Norway: Metaperspectives
Authors: Kvalsund Rune
Published: August 2019

The author identifies indicators of the pressure for deep changes in rural schools—from weight on place-conscious education to focus on tested pupil achievement in abstract school subjects—as potential research themes. Examples of such indicators are changed school structure, localization and scale; learning by acquisition or participation; educational quality or deficiency; schools as units of knowledge production; educational governance and governmentality; changed funding; migration, thinning out communities and child settlement. The context builds the larger Norwegian school reforms—silent closing of rural schools. This adds up to an overarching research theme: the cultural deconstruction of rural schools and communities as places. The author analyzes three projects covering 30 years of research on rural schools in Norway referring to metaknowledge of research themes, design, methods, concepts, and theories to trace how the footprint of cultural deconstruction of rural schools and communities, deconstructing knowledge and place, is visible in social science research as well.
A Multilevel View of Small Schools: Changing Systems in Baden-Württemberg and Vorarlberg
Authors: Kramer Caroline
Published: August 2019

Owing to demographic changes, discussions concerning the quality of small schools have increased in European countries. Two opposing schooling paradigms form this discussion’s backdrop: Advocacy of and opposition to small schools. How the discussion on the “making of schools” is conducted depends on preferred education policies and ideological affiliations, as well as on national state or economic situations. Numerous actors on a number of different spatial levels are involved in determining concrete school parameters, e.g., system structures via school planning, traffic planning, teacher allocation and organizing school routines. The multilevel view on small schools introduced here identifies an array of factors that influence the making of schools, i.e., societal processes, structures and systems, groups of actors and individuals. The author’s empirical research in Baden-Württemberg and Vorarlberg covers 25 years, and the pioneering comprehensive multilevel view on issues related to the making of small schools illustrates its importance for spatial planning.
Redefining School: Educational Spaces for Adolescents’ Engagement in Learning
Authors: Sliwka Anne , Klopsch Britta
Published: August 2019

Members of school systems around the globe recognize the challenge of educating adolescents to enable them to thrive in a rapidly changing world. They are faced with the complex task of designing educational spaces that combine more traditional instructional school settings with the “real world,” that is, the tangible world surrounding the school as well as the digital world connecting schools to the wider world. This contribution shows how adolescent students’ engagement in learning can be supported by redefining schools’ settings for learning and by designing hybrid spaces that provide complex, authentic, and demanding tasks in real-life settings to enable deeper learning.
Displacing Workers Between Companies
Authors: Sandoz Laure
Published: August 2019

The fourth chapter explores the role of the private sector in managing the mobility of workers. Interactions between service providers, companies, and workers are examined in order to shed light on the mechanisms that enable companies to access a flexible workforce. Building on interviews, ethnographic observations, and the author’s personal experience, the analysis shows that the recruitment of qualified workers relies on mobility infrastructure composed of intermediaries such as headhunters, relocation agents, consultants, and short-term labour providers. The main role of these intermediaries is to facilitate corporate access to workers who can be immediately efficient, thus reducing the need for employers to invest in training employees. Efficiency, however, means more than skills in this context, since it often implies evaluating a candidate’s social background, lifestyle, values, and perceived cultural attributes. In addition, the recent emergence and rapid growth of a migration industry specialised in securing short-term contracts for skilled workers creates new norms and constraints for employees. By facilitating mobility, these intermediaries have trivialised it. In some sectors, constant mobility has become a condition for career success. Individuals rather than institutions assume the difficulties associated with frequent mobility. Such constraints create new challenges for reconciling work with private life, as well as new uncertainties and forms of precariousness, even in well-paid and socially valued professions.
Resummed photon spectrum from dark matter annihilation for intermediate and narrow energy resolution
Authors: Beneke M. , Broggio A. , Hasner C. , Urban K. , Vollmann M.
Published: August 2019

Abstract

The annihilation cross section of weakly interacting TeV scale dark matter particles χ
0 into photons is affected by large quantum corrections due to electroweak Sudakov logarithms and the Sommerfeld effect. We extend our previous work on the resummation of the semi-inclusive photon energy spectrum in χ
0
χ
0 → γ + X in the vicinity of the maximal photon energy E

γ
= m

χ
with NLL’ accuracy from the case of narrow photon energy resolution

$$ {E}_{\mathrm{res}}^{\gamma } $$

E
res
γ

of order

$$ {m}_W^2/{m}_{\chi } $$

m
W
2

/

m
χ

to intermediate resolution of order

$$ {E}_{\mathrm{res}}^{\gamma}\sim {m}_W $$

E
res
γ

∼

m
W

. We also provide details on the previous narrow resolution calculation. The two calculations, performed in different effective field theory set-ups for the wino dark matter model, are then shown to match well, providing an accurate representation up to energy resolutions of about 300 GeV.
Phase-contrast magnetic resonance imaging to assess renal perfusion: a systematic review and statement paper
Authors: Villa Giulia , Ringgaard Steffen , Hermann Ingo , Noble Rebecca , Brambilla Paolo , Khatir Dinah S. , Zöllner Frank G. , Francis Susan T. , Selby Nicholas M. , Remuzzi Andrea , Caroli Anna
Published: August 2019

Objective

Phase-contrast magnetic resonance imaging (PC-MRI) is a non-invasive method used to compute blood flow velocity and volume. This systematic review aims to discuss the current status of renal PC-MRI and provide practical recommendations which could inform future clinical studies and its adoption in clinical practice.

Methodology

A comprehensive search of all the PC-MRI studies in human healthy subjects or patients related to the kidneys was performed.

Results

A total of 39 studies were included in which PC-MRI was used to measure renal blood flow (RBF) alongside other derivative hemodynamic parameters. PC-MRI generally showed good correlation with gold standard methods of RBF measurement, both in vitro and in vivo, and good reproducibility. Despite PC-MRI not being routinely used in clinical practice, there are several clinical studies showing its potential to support diagnosis and monitoring of renal diseases, in particular renovascular disease, chronic kidney disease and autosomal dominant polycystic kidney disease.

Discussion

Renal PC-MRI shows promise as a non-invasive technique to reliably measure RBF, both in healthy volunteers and in patients with renal disease. Future multicentric studies are needed to provide definitive normative ranges and to demonstrate the clinical potential of PC-MRI, likely as part of a multi-parametric renal MRI protocol.
Adolescents and their aspirations for private car-based transport
Authors: Hopkins Debbie , García Bengoechea Enrique , Mandic Sandra
Published: August 2019

The need to transition away from the current car-dominated transport system is well documented in sustainability, health and transportation literatures. Despite growing interest in active and public transport modes, the car still dominates travel preferences for most age groups. There is, however, some evidence of declining preferences for car-based travel for younger generations. In this paper, we use empirical material gathered through a mixed methods study of high school students in Dunedin, New Zealand, to explore the aspirations of adolescents for private car-based transport. We present and interpret findings from a quantitative survey of high school students (n = 1240) and qualitative focus groups (n = 10 focus groups, 54 participants). Contrary to somewhat optimistic reports of reduced aspiration for driving and cars, we find evidence of ongoing preference for car-based transport, and intentions to learn to drive amongst the cohort of young urban millennials. The findings signal the importance of socialisation processes and everyday travel decisions (e.g. mode choice) for long term aspirations to replicate practices of automobility. Such findings have important implications for interventions to increase non-motorised mobilities, and reduce dependence on private vehicles across the transport system.
Hypergravity-induced plastic alteration of the vestibulo-sympathetic reflex involves decrease in responsiveness of CAMK2-expressing neurons in the vestibular nuclear complex
Authors: Abe Chikara , Yamaoka Yusuke , Maejima Yui , Mikami Tomoe , Morita Hironobu
Published: August 2019

The vestibular system contributes to not only eye movement and posture but also the sympathetic response. Plastic alteration of the vestibulo-sympathetic reflex is induced by hypergravity load; however, the mechanism remains unknown. Here, we examined 2 g-induced changing in responsiveness of CAMK2-expressing neurons in the vestibular nucleus complex using optogenetic tools. The excitatory photostimulation of the CAMK2-expressing neurons in the unilateral vestibular nuclear complex induced body tilt to the contralateral side, while inhibitory photostimulation showed the opposite response. Photoactivation of either cell body or the axonal terminal in the rostral ventrolateral medulla showed sympathoexcitation followed by the pressor response. Furthermore, this response was significantly attenuated (49.8 ± 4%) after the 1st day of 2 g loading, and this value was further reduced by the 5th day (22.4 ± 3%), suggesting that 2 g-induced attenuation of the vestibulo-sympathetic reflex involves at least decrease in responsiveness of CAMK2-expressing neurons in the vestibular nuclear complex.
White matter alterations in early‐stage Alzheimer's disease: A tract‐specific study
Authors: Wen Qiuting , Mustafi Sourajit M. , Li Junjie , Risacher Shannon L. , Tallman Eileen , Brown Steven A. , West John D. , Harezlak Jaroslaw , Farlow Martin R. , Unverzagt Frederick W. , Gao Sujuan , Apostolova Liana G. , Saykin Andrew J. , Wu Yu‐Chien
Published: August 2019

Introduction

Diffusion magnetic resonance imaging may allow for microscopic characterization of white matter degeneration in early stages of Alzheimer's disease.

Methods

Multishell Diffusion magnetic resonance imaging data were acquired from 100 participants (40 cognitively normal, 38 with subjective cognitive decline, and 22 with mild cognitive impairment [MCI]). White matter microscopic degeneration in 27 major tracts of interest was assessed using diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging, and q‐space imaging.

Results

Lower DTI fractional anisotropy and higher radial diffusivity were observed in the cingulum, thalamic radiation, and forceps major of participants with MCI. These tracts of interest also had the highest predictive power to discriminate groups. Diffusion metrics were associated with cognitive performance, particularly Rey Auditory Verbal Learning Test immediate recall, with the highest association observed in participants with MCI.

Discussion

While DTI was the most sensitive, neurite orientation dispersion and density imaging and q‐space imaging complementarily characterized reduced axonal density accompanied with dispersed and less restricted white matter microstructures.
Reconsidering frameworks of Alzheimer's dementia when assessing psychosocial outcomes
Authors: Gaugler Joseph E. , Bain Lisa J. , Mitchell Lauren , Finlay Jessica , Fazio Sam , Jutkowitz Eric ,   the Alzheimer's Association Psychosocial Measurement Workgroup, Banerjee Sube , Butrum Kim , Fazio Sam , Gaugler Joseph , Gitlin Laura , Hodgson Nancy , Kallmyer Beth , Le Meyer Oanh , Logsdon Rebecca , Maslow Katie , Zimmerman Sheryl
Published: August 2019

The purpose of this introductory article to the special issue on psychosocial outcome measures in Alzheimer's & Dementia: Translational Research & Clinical Interventions is to outline new frameworks to more effectively capture and measure the full range of how people living with Alzheimer's dementia and their family caregivers experience the disease process. Specifically, we consider the strengths and weaknesses of alternative perspectives, including person‐centered, strength‐based, and resilience‐focused approaches that may complement and extend the dominant deficit paradigm to reflect the entirety of the dementia experience. Our aim is to encourage innovative methods to measure psychosocial aspects of Alzheimer's dementia and caregiving that have not yet received sufficient attention, including resources (e.g., services and supports) and positive caregiver and care recipient outcomes (e.g., positive mood and adaptation).
Navigating normativities: Gender and sexuality in text and talk
Authors: Hall Kira , Levon Erez , Milani Tommaso M.
Published: August 2019

This special issue was born out of a conversation initiated at a panel organized by two of us at the ninth biannual meeting of the International Gender and Language Association (IGALA), held at City University of Hong Kong in May 2016. The principal goal of the panel was to stimulate an academic discussion on the role of normativity and antinormativity in language, gender, and sexuality research in response to a series of critical interventions in cultural studies regarding some of the tenets underpinning queer theory (see Wiegman 2012; Penney 2014; Wiegman & Wilson 2015). It was our belief that sociolinguistics—with its focus on situated interpretations of social practice—has much to contribute, both theoretically and empirically, to these debates within cultural studies. This special issue is an initial attempt at articulating what such a contribution would be.
Nonmonotonic Postdeglacial Relative Sea Level Changes at the Aftermath of Marinoan (635 Ma) Snowball Earth Meltdown
Authors: Irie Yoshiya , Nakada Masao , Okuno Jun'ichi , Bao Huiming
Published: August 2019

Marinoan snowball Earth offers us a set of sedimentary and geochemical records for exploring glacial isostatic adjustment (GIA) associated with one of the most severe glaciations in Earth history. An accurate prediction of GIA‐based relative sea level (RSL) change associated with a snowball Earth meltdown will help to explore sedimentary records for RSL changes and to place independent constraints on mantle viscosity and on the durations of syndeglaciation (Td) and cap carbonate deposition. Here we mainly examine postdeglacial RSL change characterized by an RSL drop and a resumed transgression inferred from the cap dolostones on the continental shelf in south China. Such a nonmonotonic RSL behavior may be a diagnostic GIA signal for the Marinoan deglaciation resulting from a significantly longer postdeglacial GIA response than that for the last deglaciation. A postdeglacial RSL drop followed by transgression in south China, which is significantly affected by Earth's rotation, is predicted over the continental shelf for models with Td ≤ 20 kyr and a deep mantle viscosity of ~5 × 1022 Pa s regardless of the upper mantle viscosity. The inferred GIA model also explains the postdeglacial RSL changes such as sedimentary‐inferred RSL drops on the continental shelf in northwestern Canada and California at low‐latitude regions insignificantly affected by Earth's rotation. Furthermore, the good match between the predicted and observed RSL changes in south China suggests an approximate duration of ~50 kyr for the Marinoan 17O depletion event, an atmospheric event linked to the post‐Marinoan drawdown of CO2 and the concurrent rise of O2.
Parameter Sensitivity Analysis for Computationally Intensive Spatially Distributed Dynamical Environmental Systems Models
Authors: Huo Xueli , Gupta Hoshin , Niu Guo‐Yue , Gong Wei , Duan Qingyun
Published: August 2019

Dynamical environmental systems models are highly parameterized, having large numbers of parameters whose values are uncertain. For spatially distributed continental‐scale applications, such models must be run for very large numbers of grid locations. To calibrate such models, it is useful to be able to perform parameter screening, via sensitivity analysis, to identify the most important parameters. However, since this typically requires the models to be run for a large number of sampled parameter combinations, the computational burden can be huge. To make such an investigation computationally feasible, we propose a novel approach to combining spatial sampling with parameter sampling and test it for the Noah‐MP land surface model applied across the continental United States, focusing on gross primary production and flux of latent heat simulations for two vegetation types. Our approach uses (a) progressive Latin hypercube sampling to sample at four grid levels and four parameter levels, (b) a recently developed grouping‐based sensitivity analysis approach that ranks parameters by importance group rather than individually, and (c) a measure of robustness to grid and parameter sampling variability. The results show that a relatively small grid sample size (i.e., 5% of the total grids) and small parameter sample size (i.e., 5 times the number of parameters) are sufficient to identify the most important parameters, with very high robustness to grid sampling variability and a medium level of robustness to parameter sampling variability. The results ensure a dramatic reduction in computational costs for such studies.
Unified Linear Stability Analysis for Thermal Convections in Spherical Shells Under Different Boundary Conditions and Heating Modes
Authors: Yu Hongzheng , Wang Shimin
Published: August 2019

Layered interior structure of most planets may be well approximated by spherical shells. An important subject for analyzing planet thermal structure and evolution is to determine the transitional condition from heat conduction dominated mechanism to thermal convection dominated mechanism inside a spherical shell, which can be accomplished through linear stability analysis. In this paper, we propose an analytical solution in terms of Frobenius series to the linear stability analysis that systematically unifies various boundary conditions, heating modes, and shell geometries characterized by inner‐out radius ratio. The analysis is eventually reduced to solving the critical Rayleigh number together with its corresponding spherical harmonic degree from a vanishing determinant of sixth order, and formulas for calculating the elements of the determinant are explicitly provided. The obtained high‐accuracy results clearly show that thermal instability depends strongly on the constraining strength posed by the boundary conditions, heating modes, and shell geometry. The critical Rayleigh number generally decreases with increasing internal heating fraction and inner‐out radius ratio, as well as with switches from fixed to free‐slip or from isothermal to constant heat flux in boundary conditions, whereas remarkable exceptional cases do exist. A thorough analysis is provided to fully explain the general trends and exceptional cases, which uncovers the complicated interplay between shell geometry, heating modes, and boundary conditions, and thus substantially improves our understanding of the underlying physics for thermal convections in spherical shells. Flow streamlines and perturbation temperature distributions for some typical cases of axisymmetric thermal convections are presented as well.
Sinking Wastewater Triggers Deeper, Stronger Earthquakes
Authors: Morton Mary
Published: August 2019

The effects of pumping wastewater from oil and gas extractions may last a decade or more after the injections stop.
Twenty-Six AGU Members Awarded the 2019 Presidential Early Career Award
Authors: Speiser Joshua
Published: August 2019

The highest honor bestowed by the U.S. government on outstanding scientists and engineers beginning their independent careers
Phaeodaria: An Important Carrier of Particulate Organic Carbon in the Mesopelagic Twilight Zone of the North Pacific Ocean
Authors: Ikenoue Takahito , Kimoto Katsunori , Okazaki Yusuke , Sato Miyako , Honda Makio C. , Takahashi Kozo , Harada Naomi , Fujiki Tetsuichi
Published: August 2019

Phaeodaria, which comprise one group of large, single‐celled eukaryotic zooplankton, have been largely ignored by past marine biological studies because Phaeodaria and their delicate skeletons are liable to collapse. As a result, collection and quantification of specimens are difficult, and seasonal changes of phaeodarian abundance have not been thoroughly studied. The transport of biogenic elements by sinking phaeodarians has been estimated for only a few representative species. Sinking particles >1 mm in size and swimmers have traditionally been excluded when estimating sinking particle fluxes. The focus of this study is the large number of phaeodarians among the >1‐mm sinking particles collected in the western North Pacific from June 2014 to July 2015. Careful sorting by microscopic examination and chemical analyses revealed that phaeodarians accounted for up to about 10% of the organic carbon in all sinking particles and accounted for a mean of 33% of the organic carbon in the >1‐mm sinking particles. The high‐standing stocks of phaeodarians at depths of 150–1,000 m in the mesopelagic twilight zone suggested that particles sinking from the euphotic zone as aggregates and fecal pellets can be efficiently exported to the deep sea by the ballasting effect of large phaeodarian particles rich in organic carbon.
Thermohaline Evolution of the Western Mediterranean Deep Waters Since 2005: Diffusive Stages and Interannual Renewal Injections
Authors: Piñeiro S. , González‐Pola C. , Fernández‐Díaz J. M. , Balbin R.
Published: August 2019

A large production of anomalous dense water in the northwestern Mediterranean Sea during winter 2005 led to a widespread abrupt shift in Western Mediterranean deep waters characteristics. This new configuration, the so‐called Western Mediterranean Transition (WMT), involved a complex thermohaline structure that was tracked over time through a deep hydrographic station located NE of Minorca Island, sampled 37 times between 2004 and 2017. In this study, the thermohaline evolution of the WMT signal is analyzed in detail. Using a 1‐D diffusion model sensitive to double‐diffusive mixing phenomena, the contribution to the heat and salt budgets of the deep Western Mediterranean in terms of ventilation and diffusive transference from the intermediate layers above is disentangled. Results show distinct stages in the evolution of the deep waters, driven by background diffusion and intermittent injections of new waters. The progression of a multilayered structure in the deep ocean is well represented through existing parameterizations of salt fingering and diffusive layering processes and makes it possible to infer an independent estimate of regional background diffusivity consistent with current knowledge. Overall, the deep layers of the Western Mediterranean underwent substantial warming (0.059 °C) and salt increase (0.021) between 2004 and 2017, mostly dominated by injections of dense waters in the 2005–2006 and 2011–2013 periods. Thus, within the WMT period, heat uptake rate in the deep Western Mediterranean was substantially higher than that of the intermediate levels in the global ocean.
Persistent depressive symptoms, HPA-axis hyperactivity, and inflammation: the role of cognitive-affective and somatic symptoms
Authors: Iob Eleonora , Kirschbaum Clemens , Steptoe Andrew
Published: August 2019

Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity and inflammation are thought to be prominent in the aetiology of depression. Although meta-analyses have confirmed this relationship, there is considerable variability in the effect sizes across studies. This could be attributed to a differential role of such biological systems in somatic versus cognitive-affective depressive symptoms which remains largely unexplored. Furthermore, most longitudinal research to date has focused on transient rather than persistent depressive symptoms. In the current study, we investigated the associations of hair cortisol and plasma C-reactive protein (CRP) with the longitudinal persistence and dimensions (cognitive-affective versus somatic) of depressive symptoms over a 14-year period using Trait‐State‐Occasion (TSO) structural equation modelling. The data came from a large sample of older adults from the English Longitudinal Study of Ageing. Depressive symptoms were assessed from wave 1 (2002–03) to wave 8 (2016–17). Hair cortisol (N = 4761) and plasma CRP (N = 5784) were measured in wave 6 (2012–13). Covariates included demographic, socioeconomic, lifestyle, chronic disease, and medication data. Our results revealed that higher cortisol and CRP levels were significantly associated with persistent depressive symptoms across the study period. Notably, both biomarkers exhibited stronger relationships with somatic than with cognitive-affective symptoms. The associations with somatic symptoms were also independent of relevant confounding factors. In contrast, their associations with cognitive-affective symptoms were weak after adjustment for all covariates. These distinct associations reveal the importance of considering symptom-specific effects in future studies on pathophysiological mechanisms. Ultimately, this will have the potential to advance the search for biomarkers of depression and facilitate more targeted treatments.
Divergent engagements between adeno-associated viruses with their cellular receptor AAVR
Authors: Zhang Ran , Xu Guangxue , Cao Lin , Sun Zixian , He Yong , Cui Mengtian , Sun Yuna , Li Shentao , Li Huapeng , Qin Lan , Hu Mingxu , Yuan Zhengjia , Rao Zipei , Ding Wei , Rao Zihe , Lou Zhiyong
Published: August 2019

Adeno-associated virus (AAV) receptor (AAVR) is an essential receptor for the entry of multiple AAV serotypes with divergent rules; however, the mechanism remains unclear. Here, we determine the structures of the AAV1-AAVR and AAV5-AAVR complexes, revealing the molecular details by which PKD1 recognizes AAV5 and PKD2 is solely engaged with AAV1. PKD2 lies on the plateau region of the AAV1 capsid. However, the AAV5-AAVR interface is strikingly different, in which PKD1 is bound at the opposite side of the spike of the AAV5 capsid than the PKD2-interacting region of AAV1. Residues in strands F/G and the CD loop of PKD1 interact directly with AAV5, whereas residues in strands B/C/E and the BC loop of PKD2 make contact with AAV1. These findings further the understanding of the distinct mechanisms by which AAVR recognizes various AAV serotypes and provide an example of a single receptor engaging multiple viral serotypes with divergent rules.
Cytoplasmic DAXX drives SQSTM1/p62 phase condensation to activate Nrf2-mediated stress response
Authors: Yang Yi , Willis Thea L. , Button Robert W. , Strang Conor J. , Fu Yuhua , Wen Xue , Grayson Portia R. C. , Evans Tracey , Sipthorpe Rebecca J. , Roberts Sheridan L. , Hu Bing , Zhang Jianke , Lu Boxun , Luo Shouqing
Published: August 2019

Autophagy cargo recognition and clearance are essential for intracellular protein quality control. SQSTM1/p62 sequesters intracellular aberrant proteins and mediates cargo delivery for their selective autophagic degradation. The formation of p62 non-membrane-bound liquid compartments is critical for its function as a cargo receptor. The regulation of p62 phase separation/condensation has yet been poorly characterised. Using an unbiased yeast two-hybrid screening and complementary approaches, we found that DAXX physically interacts with p62. Cytoplasmic DAXX promotes p62 puncta formation. We further elucidate that DAXX drives p62 liquid phase condensation by inducing p62 oligomerisation. This effect promotes p62 recruitment of Keap1 and subsequent Nrf2-mediated stress response. The present study suggests a mechanism of p62 phase condensation by a protein interaction, and indicates that DAXX regulates redox homoeostasis, providing a mechanistic insight into the prosurvival function of DAXX.
Structural basis for lamin assembly at the molecular level
Authors: Ahn Jinsook , Jo Inseong , Kang So-mi , Hong Seokho , Kim Suhyeon , Jeong Soyeon , Kim Yong-Hak , Park Bum-Joon , Ha Nam-Chul
Published: August 2019

Nuclear structure and function are governed by lamins, which are intermediate filaments that mostly consist of α-helices. Different lamin assembly models have been proposed based on low resolution and fragmented structures. However, their assembly mechanisms are still poorly understood at the molecular level. Here, we present the crystal structure of a long human lamin fragment at 3.2 Å resolution that allows the visualization of the features of the full-length protein. The structure shows an anti-parallel arrangement of the two coiled-coil dimers, which is important for the assembly process. We further discover an interaction between the lamin dimers by using chemical cross-linking and mass spectrometry analysis. Based on these two interactions, we propose a molecular mechanism for lamin assembly that is in agreement with a recent model representing the native state and could explain pathological mutations. Our findings also provide the molecular basis for assembly mechanisms of other intermediate filaments.
Three-dimensional solitary waves with electrically tunable direction of propagation in nematics
Authors: Li Bing-Xiang , Xiao Rui-Lin , Paladugu Sathyanarayana , Shiyanovskii Sergij V. , Lavrentovich Oleg D.
Published: August 2019

Production of stable multidimensional solitary waves is a grand challenge in modern science. Steering their propagation is an even harder problem. Here we demonstrate three-dimensional solitary waves in a nematic, trajectories of which can be steered by the electric field in a plane perpendicular to the field. The steering does not modify the properties of the background that remains uniform. These localized waves, called director bullets, are topologically unprotected multidimensional solitons of (3 + 2)D type that show fore-aft and right-left asymmetry with respect to the background molecular director; the symmetry is controlled by the field. Besides adding a whole dimension to the propagation direction and enabling controlled steering, the solitons can lead to applications such as targeted delivery of information and micro-cargo.
Molecular basis of PIP2-dependent regulation of the Ca2+-activated chloride channel TMEM16A
Authors: Le Son C. , Jia Zhiguang , Chen Jianhan , Yang Huanghe
Published: August 2019

The calcium-activated chloride channel (CaCC) TMEM16A plays crucial roles in regulating neuronal excitability, smooth muscle contraction, fluid secretion and gut motility. While opening of TMEM16A requires binding of intracellular Ca2+, prolonged Ca2+-dependent activation results in channel desensitization or rundown, the mechanism of which is unclear. Here we show that phosphatidylinositol (4,5)-bisphosphate (PIP2) regulates TMEM16A channel activation and desensitization via binding to a putative binding site at the cytosolic interface of transmembrane segments (TMs) 3–5. We further demonstrate that the ion-conducting pore of TMEM16A is constituted of two functionally distinct modules: a Ca2+-binding module formed by TMs 6–8 and a PIP2-binding regulatory module formed by TMs 3–5, which mediate channel activation and desensitization, respectively. PIP2dissociation from the regulatory module results in ion-conducting pore collapse and subsequent channel desensitization. Our findings thus provide key insights into the mechanistic understanding of TMEM16 channel gating and lipid-dependent regulation.
Repeated semen exposure decreases cervicovaginal SIVmac251 infection in rhesus macaques
Authors: Abdulhaqq Shaheed A. , Martinez Melween , Kang Guobin , Rodriguez Idia V. , Nichols Stephanie M. , Beaumont David , Joseph Jocelin , Azzoni Livio , Yin Xiangfan , Wise Megan , Weiner David , Liu Qin , Foulkes Andrea , Münch Jan , Kirchhoff Frank , Coutifaris Christos , Tomaras Georgia D. , Sariol Carlos , Marx Preston A. , Li Qingsheng , Kraiselburd Edmundo N. , Montaner Luis J.
Published: August 2019

Semen is the vehicle for virion dissemination in the female reproductive tract (FRT) in male-to-female HIV transmission. Recent data suggests that higher frequency semen exposure is associated with activation of anti-HIV mechanisms in HIV negative sex workers. Here, we use a non-human primate (NHP) model to show that repeated vaginal exposure to semen significantly reduces subsequent infection by repeated low-dose vaginal SIVmac251 challenge. Repeated semen exposures result in lower CCR5 expression in circulating CD4+ T-cells, as well as higher expression of Mx1 (in correlation with IFNε expression) and FoxP3 in the cervicovaginal mucosa, and increased infiltration of CD4+ T-cells. Establishing in vivo evidence of competing effects of semen on transmission impacts our basic understanding of what factors may determine HIV infectivity in humans. Our results clearly indicate that repeated semen exposure can profoundly modulate the FRT microenvironment, paradoxically promoting host resistance against HIV acquisition.
Taxonomic and functional characterization of a microbial community from a volcanic englacial ecosystem in Deception Island, Antarctica
Authors: Martinez-Alonso Emma , Pena-Perez Sonia , Serrano Sandra , Garcia-Lopez Eva , Alcazar Alberto , Cid Cristina
Published: August 2019

Glaciers are populated by a large number of microorganisms including bacteria, archaea and microeukaryotes. Several factors such as solar radiation, nutrient availability and water content greatly determine the diversity and abundance of these microbial populations, the type of metabolism and the biogeochemical cycles. Three ecosystems can be differentiated in glaciers: supraglacial, subglacial and englacial ecosystems. Firstly, the supraglacial ecosystem, sunlit and oxygenated, is predominantly populated by photoautotrophic microorganisms. Secondly, the subglacial ecosystem contains a majority of chemoautotrophs that are fed on the mineral salts of the rocks and basal soil. Lastly, the englacial ecosystem is the least studied and the one that contains the smallest number of microorganisms. However, these unknown englacial microorganisms establish a food web and appear to have an active metabolism. In order to study their metabolic potentials, samples of englacial ice were taken from an Antarctic glacier. Microorganisms were analyzed by a polyphasic approach that combines a set of -omic techniques: 16S rRNA sequencing, culturomics and metaproteomics. This combination provides key information about diversity and functions of microbial populations, especially in rare habitats. Several whole essential proteins and enzymes related to metabolism and energy production, recombination and translation were found that demonstrate the existence of cellular activity at subzero temperatures. In this way it is shown that the englacial microorganisms are not quiescent, but that they maintain an active metabolism and play an important role in the glacial microbial community.
Long-term Management Effects and Temperature Sensitivity of Soil Organic Carbon in Grassland and Agricultural Soils
Authors: Ghimire Rajan , Bista Prakriti , Machado Stephen
Published: August 2019

Soil organic carbon (SOC) is integral to soil health and agroecosystem resilience. Despite much research, understanding of temperature sensitivity of SOC under long-term agricultural management is very limited. The main objective of this study was to evaluate SOC and nitrogen (N) dynamics under grasslands and winter wheat (Triticum aestivum L)-based crop rotations in the inland Pacific Northwest (IPNW), USA, and measure SOC mineralization under ambient and elevated incubation temperatures. Soil samples were collected from 0–10 and 10–20 cm depths from an undisturbed grassland (GP), winter wheat-pea (Pisum sativum L) rotations under conventional tillage (WP-CT) and no-tillage (WP-NT), and winter wheat-fallow rotation under conventional tillage (WF-CT) and analyzed for SOC and N pools. Soil samples were incubated at 20 °C and 30 °C for 10 weeks, and SOC mineralization rates were estimated using the first order kinetic model. The GP had the greatest amounts of SOC, total N (TN), and microbial biomass carbon (MBC) and WP rotations had higher inorganic N content than other treatments. The SOC mineralization at elevated incubation temperature was 72–177% more than at the ambient temperature, and the greatest effect was observed in GP. The SOC storage under a given management did not have consistent effects on soil carbon (C) and N mineralization under elevated temperature. However, soil disturbance under WP-CT and WF-CT accelerated SOC mineralization leading to soil C loss. Reducing tillage, integrating legumes into crop rotations, and growing perennial grasses could minimize SOC loss and have the potential to improve soil health and agroecosystem resilience under projected climate warming.