bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating long‐term treatment effects in observational data: A comparison of the performance of different methods under real‐world uncertainty
Authors: Newsome Simon J. , Keogh Ruth H. , Daniel Rhian M.
Published: April 2018

In the presence of time‐dependent confounding, there are several methods available to estimate treatment effects. With correctly specified models and appropriate structural assumptions, any of these methods could provide consistent effect estimates, but with real‐world data, all models will be misspecified and it is difficult to know if assumptions are violated.

In this paper, we investigate five methods: inverse probability weighting of marginal structural models, history‐adjusted marginal structural models, sequential conditional mean models, g‐computation formula, and g‐estimation of structural nested models. This work is motivated by an investigation of the effects of treatments in cystic fibrosis using the UK Cystic Fibrosis Registry data focussing on two outcomes: lung function (continuous outcome) and annual number of days receiving intravenous antibiotics (count outcome). We identified five features of this data that may affect the performance of the methods: misspecification of the causal null, long‐term treatment effects, effect modification by time‐varying covariates, misspecification of the direction of causal pathways, and censoring.

In simulation studies, under ideal settings, all five methods provide consistent estimates of the treatment effect with little difference between methods. However, all methods performed poorly under some settings, highlighting the importance of using appropriate methods based on the data available. Furthermore, with the count outcome, the issue of non‐collapsibility makes comparison between methods delivering marginal and conditional effects difficult. In many situations, we would recommend using more than one of the available methods for analysis, as if the effect estimates are very different, this would indicate potential issues with the analyses.
Subgroups from regression trees with adjustment for prognostic effects and postselection inference
Authors: Loh Wei‐Yin , Man Michael , Wang Shuaicheng
Published: April 2018

Identification of subgroups with differential treatment effects in randomized trials is attracting much attention. Many methods use regression tree algorithms. This article addresses 2 important questions arising from the subgroups: how to ensure that treatment effects in subgroups are not confounded with effects of prognostic variables and how to determine the statistical significance of treatment effects in the subgroups. We address the first question by selectively including linear prognostic effects in the subgroups in a regression tree model. The second question is more difficult because it falls within the subject of postselection inference. We use a bootstrap technique to calibrate normal‐theory t intervals so that their expected coverage probability, averaged over all the subgroups in a fitted model, approximates the desired confidence level. It can also provide simultaneous confidence intervals for all subgroups. The first solution is implemented in the GUIDE algorithm and is applicable to data with missing covariate values, 2 or more treatment arms, and outcomes subject to right censoring. Bootstrap calibration is applicable to any subgroup identification method; it is not restricted to regression tree models. Two real examples are used for illustration: a diabetes trial where the outcomes are completely observed but some covariate values are missing and a breast cancer trial where the outcome is right censored.
On strong mutation and the theory of subsuming logic‐based mutants
Authors: Lindström Birgitta , Márki András
Published: April 2018

Redundant mutants might cause problems when benchmarking since testing techniques can get high scores without detecting any nonredundant mutants. However, removing nonredundant mutants might cause similar problems. Subsumed mutants are per definition also redundant since no additional tests are required to detect them once all other mutants are detected. We focus on relational operator replacement (ROR) and conditional operator replacement mutants. Subsumption relations between ROR mutants are defined by fault hierarchies. The fault hierarchies are proven for weak mutation but have since they were published been used with strong mutation. We prove that ROR fault hierarchies do not hold for strong mutation and show why. We also show that the probability for a random test to experience the problem can be more than 30% and that 50% of the mutants might be affected in a real software system. Finally, we show that there is a similar problem with the theory on sufficient conditional operator replacement.
Carbon Nanomaterials in Direct Liquid Fuel Cells
Authors: Du Huayun , Zhao Cindy Xinxin , Lin Jing , Guo Jiang , Wang Bin , Hu Zhen , Shao Qian , Pan Duo , Wujcik Evan K. , Guo Zhanhu
Published: April 2018

Fuel cells have attracted more attentions due to many advantages they can provide, including high energy efficiency and low environmental burden. To form a stable, low cost and efficient catalyst, we presented here the state of the art of electrocatalyst fabrication approaches, involving carbon nanotubes and their multifunctional nanocomposites incorporated with noble metals, such as Pt, Pd, Au, their binary and ternary systems. Both fuel oxidation reactions and oxygen reduction reactions were emphasized with comprehensive examples and future prospects.
Impact of ozone on claudins and tight junctions in the lungs
Authors: Kim Byeong‐Gon , Lee Pureun‐Haneul , Lee Sun‐Hye , Park Choon‐Sik , Jang An‐Soo
Published: April 2018

Claudins (CLDNs) are a major transmembrane protein component of tight junctions (TJs) in endothelia and epithelia. CLDNs are not only essential for sustaining the role of TJs in cell permeability but are also vital for cell signaling through protein‐protein interactions. Ozone induces oxidative stress and lung inflammation in humans and experimental models, but the impact of ozone on claudins remains poorly understood. This study was to determine the expression of TJ proteins, such as claudin 3, 4, 5, and 14 following ozone exposure. Mice were exposed to 0.1, 1, or 2 ppm of ozone or ambient air for 6 h for 3 days. The impact of ozone on CLDNs, Nrf2, Keap1, and reactive oxygen species (ROS) were estimated using immunoblotting, immunohistochemical staining, confocal imaging, and ELISA analysis in mice and bronchial epithelial cells. Mice exposed to ozone experienced increased airway inflammatory cell infiltration and bronchial hyper‐responsiveness compared to control mice. Additionally, CLDN3, CLDN4, ROS, Nrf2, and Keap1 protein expression increased, and lung CLDN14 protein expression decreased, in mice exposed to ozone compared with control mice. These results indicate that CLDNs are involved in airway inflammation following ozone exposure, suggesting that ozone affects TJ proteins through oxidative mechanisms.
Critical $$ \mathcal{N} $$ = (1, 1) general massive supergravity
Authors: Deger Nihat Sadik , Moutsopoulos George , Rosseel Jan
Published: April 2018

Abstract

In this paper we study the supermultiplet structure of

$$ \mathcal{N} $$

N

= (1, 1) General Massive Supergravity at non-critical and critical points of its parameter space. To do this, we first linearize the theory around its maximally supersymmetric AdS3 vacuum and obtain the full linearized Lagrangian including fermionic terms. At generic values, linearized modes can be organized as two massless and 2 massive multiplets where supersymmetry relates them in the standard way. At critical points logarithmic modes appear and we find that in three of such points some of the supersymmetry transformations are non-invertible in logarithmic multiplets. However, in the fourth critical point, there is a massive logarithmic multiplet with invertible supersymmetry transformations.
A modular approach for high-flux lactic acid production from methane in an industrial medium using engineered Methylomicrobium buryatense 5GB1
Authors: Garg Shivani , Clomburg James M , Gonzalez Ramon
Published: April 2018

Convergence of market drivers such as abundant availability of inexpensive natural gas and increasing awareness of its global warming effects have created new opportunities for the development of small-scale gas-to-liquid (GTL) conversion technologies that can efficiently utilize methane, the primary component of natural gas. Leveraging the unique ability of methanotrophs that use methane as carbon and energy source, biological GTL platforms can be envisioned that are readily deployable at remote petroleum drilling sites where large chemical GTL infrastructure is uneconomical to set-up. Methylomicrobium buryatense, an obligate methanotroph, has gained traction as a potential industrial methanotrophic host because of availability of genetic tools and recent advances in its metabolic engineering. However, progress is impeded by low strain performance and lack of an industrial medium. In this study, we first established a small-scale cultivation platform using Hungate tubes for growth of M. buryatense at medium-to-high-throughput that also enabled 2X faster growth compared to that obtained in traditional glass serum bottles. Then, employing a synthetic biology approach we engineered M. buryatense with varying promoter (inducible and constitutive) and ribosome-binding site combinations, and obtained a strain capable of producing l-lactate from methane at a flux 14-fold higher than previously reported. Finally, we demonstrated l-lactate production in an industrial medium by replacing nitrate with less-expensive ammonium as the nitrogen source. Under these conditions, l-lactate was synthesized at a flux approximately 50-fold higher than that reported previously in a bioreactor system while achieving a titer of 0.6 g/L. These findings position M. buryatense closer to becoming an industrial host strain of choice, and pave new avenues for accelerating methane-to-chemical conversion using synthetic biology.
What to Do with a Second Chance in Life? Long‐Term Experiences of Non‐carriers of Huntington's Disease
Authors: Winnberg Elisabeth , Winnberg Ulrika , Pohlkamp Lilian , Hagberg Anette
Published: April 2018

Little is known about how people's lives are influenced when going from a 50% risk status of Huntington's disease (HD) to no risk after performing predictive testing. In this study, 20 interviews were conducted to explore the long‐term (> 5 years) experiences after receiving predictive test results as a non‐carrier of HD. The results showed a broad variety of both positive and negative reactions. The most prominent positive reaction reported was feelings of relief and gratitude, of not carrying the HD mutation for themselves and for their children. Also, the non‐carrier status promoted in some individuals’ significant life changes such as a wishing to have (more) children, pursuing a career or breaking up from an unhappy relationship. However, negative reactions on their psychological well‐being were also described. Some had experienced psychological pressure of needing to do something extraordinary in their lives; others expressed feelings of guilt towards affected or untested siblings, resulting in sadness or clinical depression. The new genetic risk status could generate a need of re‐orientation, a process that for some persons took several years to accomplish. The results of the present study show the importance of offering long‐term post‐result counselling for non‐carriers in order to deal with the psychological consequences that may follow predictive testing.
Local well-posedness for quasi-linear NLS with large Cauchy data on the circle
Authors: Feola R. , Iandoli F.
Published: April 2018

We prove local in time well-posedness for a large class of quasilinear Hamiltonian, or parity preserving, Schrödinger equations on the circle. After a paralinearization of the equation, we perform several paradifferential changes of coordinates in order to transform the system into a paradifferential one with symbols which, at the positive order, are constant and purely imaginary. This allows to obtain a priori energy estimates on the Sobolev norms of the solutions.
Love, Struggle, and Compromises: The Political Seriousness of Nairobi Underground Hip Hop
Authors: Peck RaShelle R.
Published: April 2018

This article explores the characteristics of Nairobi underground hip hop that fit under a common theme of what I term as the music’s “political seriousness,” which is the common notion that the music must be substantive, thought-provoking, socially critical, and never vacuous. This political seriousness is composed of four characteristics: Mau Mau gendered legacies, political love, a reliance on neoliberalism, and a critique of the state. Hip hop’s goal is to make a political space that both proves its worth and remedies Kenya’s flawed polity. This is an imperfect endeavor, as its dependence on late capitalism, normative gender constructions, and conventional understandings of the Mau Mau war contribute to rap’s troubling tendencies. Nonetheless, these artists regard hip hop as authentic or real music because it advocates for the economically disenfranchised, contributes to Kenyan social commentary, and participates in an imagined global hip hop culture.
The Sensitivity of Three Versions of the Padua Inventory to Measuring Treatment Outcome and Their Relationship to the Yale-Brown Obsessive Compulsive Scale
Authors: Baraby Louis-Philippe , Audet Jean-Sébastien , Aardema Frederick
Published: April 2018

The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and different versions of the Padua Inventory (PI) are frequently used instruments to measure symptoms of obsessive-compulsive disorder (OCD). However, little is known of how these different versions of the PI compare to each other in their sensitivity to measuring treatment outcome, and there is currently no adequate explanation to account for the weak relationships between self-report measures and the Y-BOCS. This study aimed to investigate the sensitivity of these measures to treatment outcome, and to examine whether differences in how they measure symptom severity can explain the weak relationships. Hypotheses were: (1) the Y-BOCS would be significantly more sensitive to measuring treatment outcome than the PI versions; (2) correlations between the measures would be significantly stronger for change scores as compared to relations measured at a single point in time; (3) weak relationships can be explained by the PI measuring symptom severity based on content and the Y-BOCS measuring symptoms, independent of content. Results showed that the Y-BOCS was significantly more sensitive to measuring treatment outcome than the PI versions, while differences between the questionnaires in which severity is measured can provide a partial account for why weak relations are observed between these measures.
The Impact of the Medicaid Healthcare-Associated Condition Program on Mediastinitis Following Coronary Artery Bypass Graft
Authors: Hsu Heather E. , Kawai Alison Tse , Wang Rui , Jentzsch Maximilian S. , Rhee Chanu , Horan Kelly , Jin Robert , Goldmann Donald , Lee Grace M.
Published: April 2018

OBJECTIVE

In 2012, the Centers for Medicare and Medicaid Services expanded a 2008 program that eliminated additional Medicare payment for mediastinitis following coronary artery bypass graft (CABG) to include Medicaid. We aimed to evaluate the impact of this Medicaid program on mediastinitis rates reported by the National Healthcare Safety Network (NHSN) compared with the rates of a condition not targeted by the program, deep-space surgical site infection (SSI) after knee replacement.

DESIGN

Interrupted time series with comparison group.

METHODS

We included surveillance data from nonfederal acute-care hospitals participating in the NHSN and reporting CABG or knee replacement outcomes from January 2009 through June 2017. We examined the Medicaid program’s impact on NHSN-reported infection rates, adjusting for secular trends. The data analysis used generalized estimating equations with robust sandwich variance estimators.

RESULTS

During the study period, 196 study hospitals reported 273,984 CABGs to the NHSN, resulting in 970 mediastinitis cases (0.35%), and 294 hospitals reported 555,395 knee replacements, with 1,751 resultant deep-space SSIs (0.32%). There was no significant change in incidence of either condition during the study. Mediastinitis models showed no effect of the 2012 Medicaid program on either secular trend during the postprogram versus preprogram periods (P=.70) or an immediate program effect (P=.83). Results were similar in sensitivity analyses when adjusting for hospital characteristics, restricting to hospitals with consistent NHSN reporting or incorporating a program implementation roll-in period. Knee replacement models also showed no program effect.

CONCLUSIONS

The 2012 Medicaid program to eliminate additional payments for mediastinitis following CABG had no impact on reported mediastinitis rates.

Infect Control Hosp Epidemiol 2018;39:694–700
Meriones unguiculatus infected by Haemonchus contortus: evaluation of different experimental protocols
Authors: Gressler L.T. , Grando T.H. , Machado do Carmo G. , Vaucher R.A. , Stefani L.M. , Monteiro S.G.
Published: April 2018

Many important studies on resistance reversion, anthelmintic efficacy and, especially, new molecules with antiparasitic effects are performed in laboratories using gerbils (Meriones unguiculatus) as the experimental model. This study aimed to evaluate the use of corticosteroids (dexamethasone and methylprednisolone acetate) in gerbils experimentally infected with different doses of infective larvae (sheathed or exsheathed) of Haemonchus contortus. In the first experiment, 28 gerbils were divided into seven groups infected by 2–6 × 103 larvae, with or without immunosuppression using corticosteroids. In the second experiment, eight gerbils were divided into two groups infected by 2 × 103 sheathed or exsheathed larvae. For the third assay, seven immunosuppressed gerbils were infected with 2 × 103 sheathed larvae and were killed 15 days post infection (PI). The highest number of parasites was recovered from methylprednisolone-immunosuppressed animals. We observed red and white blood cell alterations and biochemical parameters in infected animals that had undergone immunosuppression with methylprednisolone. We highlight that in the first and second experiments a satisfactory number of worms was recovered using sheathed larvae and immunocompetent animals. When exsheathed larvae were used, the number of worms recovered was unsatisfactory. A considerable larval burden was recovered from immunosuppressed gerbils 15 days PI, and body weight did not influence establishment of larvae.
A Series of Footnotes to Plato's Philosophers
Authors: Cherry Kevin M.
Published: April 2018

In her magisterial Plato's Philosophers, Catherine Zuckert presents a radically new interpretation of Plato's dialogues. In doing so, she insists we must overcome reading them through the lens of Aristotle, whose influence has obscured the true nature of Plato's philosophy. However, in her works dealing with Aristotle's political science, Zuckert indicates several advantages of his approach to understanding politics. In this article, I explore the reasons why Zuckert finds Aristotle a problematic guide to Plato's philosophy as well as what she sees as the character and benefits of Aristotle's political theory. I conclude by suggesting a possible reconciliation between Zuckert's Aristotle and her Plato, insofar as both the Socrates whom Plato made his hero and Aristotle agree that political communities will rarely direct citizens toward virtue by means of law and that we must instead look to informal means of doing so.
Dramaturgy of the Body: Marcello Moretti's Construction of Arlecchino at the Piccolo Teatro of Milan
Authors: Houle Gabrielle
Published: April 2018

In this article Gabrielle Houle examines the dramaturgical process that actor Marcello Moretti applied to his creation of Arlecchino's body in Giorgio Strehler's globally acclaimed productions of The Servant of Two Masters at the Piccolo Teatro of Milan between 1947 and 1960. She provides a critical analysis of Moretti's interdisciplinary and trans-historical research and creative process, including his study of iconographic representations of the commedia dell’arte, his observation of farmers in Padua in the mid-twentieth century, and the connections he made between his life experiences and his understanding of Arlecchino. She then examines Moretti's acting style, signature postures, and footwork, both as the international press described them and as she observed them in a video recording and in photographs of the productions. The article, based on extensive archival research at the Piccolo Teatro and on interviews with artists who knew both Moretti and Strehler, concludes with a discussion of Moretti's legacy within and beyond Italy. Gabrielle Houle is a theatre scholar, educator, and artist specializing in the recent staging history of the commedia dell’arte, contemporary mask-making practices, and masked performance. She has taught in several Canadian universities, and is a member of the Centre for Oral History and Tradition at the University of Lethbridge, where she is also an Adjunct Assistant Professor.
Active Experiencing in Postdramatic Performance: Affective Memory and Quarantine Theatre's Wallflower
Authors: Crossley Tracy
Published: April 2018

Postdramatic approaches to performance and Stanislavsky's methodology seemingly occupy divergent performance traditions. Nonetheless, both traditions often require performers to mine their own lives (albeit to different ends) and operate in an experiential realm that demands responsiveness to and within the live moment of performing. Tracy Crossley explores this realm through an analysis of Quarantine Theatre's Wallflower (2015), an example of postdramatic practice that blends a poetics of failure with a psycho - physical dramaturgical approach that can be aligned with Stanislavsky's concepts of affective memory and active analysis.Wallflower provides a useful case study of practice that challenges the binary opposition between the dramatic and postdramatic prevalent in theatre and performance studies scholarship. Aspects of Stanislavsky's system, nuanced by cognitive neuroscience, can expand the theorization of postdramatic theatre, which in turn generates techniques that can prove valuable in the rehearsal of dramatic theatre itself. Tracy Crossley is a Senior Lecturer in Theatre and Performance at the University of Salford, Manchester. She is currently developing a practical handbook, Making Postdramatic Theatre, for Digital Theatre Plus.
Displaying the Mizrahi Identity in Autobiographical Performances: Body, Food, and Documents
Authors: Shem-Tov Naphtaly
Published: April 2018

In this article Naphtaly Shem-Tov examines three Mizrahi autobiographical performances in Israel, exploring how they construct Mizrahi identity in different ways. The term ‘Mizrahi’ or ‘Mizrahim’ refers to Jews and their descendants originating in the Muslim and Arab countries. Although Mizrahim make up approximately half the Israeli population, their ethnic identity and culture are considered outside the dominant Israeli Western cultural orientation. The three autobiographical performances discussed here challenge these preconceptions and present an alternative, assertive identity for the Mizrahi community. The performers incorporate real elements – physical virtuosity, the preparation and serving of food, and the use of official documentation and personal records – to blur the lines between fiction and reality, and to draw attention to the different forms of oppression exerted on the Mizrahi identity. Naphtaly Shem-Tov is Senior Lecturer in the Department of Literature, Language and the Arts at the Open University of Israel. His publications include Acco Festival: Between Celebration and Confrontation (Boston: Academic Studies Press, 2016).
Is the ‘Animal-Event’ Possible? Animal Precariousness and Moral Indeterminacy in Performance
Authors: Pefanis George P.
Published: April 2018

In this article, George P. Pefanis discusses two major aspects of the ‘event’, as formed and developed in late Derridean philosophy – namely, the ‘possibility of the impossible’ and the ‘experience of perhaps’. These aspects are examined in order to reveal the potential for precariousness and uncertainty engendered by performance art, as in the case of the animal-event. With its increased degree of indeterminacy and its projected singular, here-and-now character, performance art could leave open the way to the ‘other’, the unpredictable, and the unexpected that is the ‘animal-event’, since an animal can never be fully controlled or have its behaviour predicted by the theatre mechanism. Two performances are taken as case studies to demonstrate this: the emblematic I Like America and America Likes Me by Joseph Beuys (René Block Gallery, New York, 1974), and Dragon Heads by Marina Abramović (Museum of Modern Art, Oxford, 1990). It is argued that both cases pose certain moral issues around the presence of animals on the stage. George P. Pefanis is Associate Professor in the Department of Theatre Studies at the National and Kapodistreian University of Athens, and also teaches theatre and cinema history at the Open University of Greece and Cyprus. His publications include Adventures of Representation: Scenes of Theory II, Spectres of Theatre: Scenes of Theory III (both 2013) and Theatre Adherents and Philosophers (Athens, 2016). In 2006, he received the award for best book in the study of theatre for The Kingdom of Eugena (2005).
On the typical size and cancellations among the coefficients of some modular forms
Authors: LUCA FLORIAN , RADZIWIŁŁ MAKSYM , SHPARLINSKI IGOR E.
Published: April 2018

We obtain a nontrivial upper bound for almost all elements of the sequences of real numbers which are multiplicative and at the prime indices are distributed according to the Sato–Tate density. Examples of such sequences come from coefficients of severalL-functions of elliptic curves and modular forms. In particular, we show that |τ(n)| ⩽n11/2(logn)−1/2+o(1)for a set ofnof asymptotic density 1, where τ(n) is the Ramanujan τ function while the standard argument yields log 2 instead of −1/2 in the power of the logarithm. Another consequence of our result is that in the number of representations ofnby a binary quadratic form one has slightly more than square-root cancellations for almost all integersn.

In addition, we obtain a central limit theorem for such sequences, assuming a weak hypothesis on the rate of convergence to the Sato–Tate law. For Fourier coefficients of primitive holomorphic cusp forms such a hypothesis is known conditionally and might be within reach unconditionally using the currently established potential automorphy.
Comparison of Thermal Manikin Modeling and Human Subjects’ Response During Use of Cooling Devices Under Personal Protective Ensembles in the Heat
Authors: Quinn Tyler , Kim Jung-Hyun , Seo Yongsuk , Coca Aitor
Published: April 2018

Introduction

Personal protective equipment (PPE) recommended for use in West Africa during the Ebola outbreak increased risk for heat illness, and countermeasures addressing this issue would be valuable.

Hypothesis/Problem

The purpose of this study was to examine the physiological impact and heat perception of four different personal cooling devices (PCDs) under impermeable PPE during low-intensity exercise in a hot and humid environment using thermal manikin modeling and human testing.

Methods

Six healthy male subjects walked on a treadmill in a hot/humid environment (32°C/92% relative humidity [RH]) at three metabolic equivalents (METs) for 60 minutes wearing PPE recommended for use in West Africa and one of four different personal cooling devices (PCDs; PCD1, PCD2, PCD3, and PCD4) or no PCD for control (CON). The same ensembles were tested with thermal manikin modeling software in the same conditions to compare the results.

Results

All PCDs seemed to reduce physiological heat stress characteristics when worn under PPE compared to CON. Both the manikin and human testing provided similar results in core temperature (Tc) and heat sensation (HS) in both magnitude and relationship. While the manikin and human data provided similar skin temperature (Tsk) characterization, Tskestimation by the manikin seemed to be slightly over-estimated. Weight loss, as estimated by the manikin, was under-estimated compared to the human measurement.

Conclusion

Personal cooling device use in conjunction with impermeable PPE may be advantageous in mitigating physiological and perceptual burdens of heat stress. Evaluation of PCDs worn under PPE can be done effectively via human or manikin testing; however, Tskmay be over-estimated and weight loss may be under-estimated. Thermal manikin testing of PCDs may provide fast and accurate information to persons recommending or using PCDs with PPE.

QuinnT,KimJH,SeoY,CocaA.Comparison of thermal manikin modeling and human subjects’ response during use of cooling devices under personal protective ensembles in the heat.Prehosp Disaster Med.2018;33(3):279–287.
Eddy Covariance Measurements of Methane Flux at a Tropical Peat Forest in Sarawak, Malaysian Borneo
Authors: Tang Angela C. I. , Stoy Paul C. , Hirata Ryuichi , Musin Kevin K. , Aeries Edward B. , Wenceslaus Joseph , Melling Lulie
Published: April 2018

Tropical biogenic sources are a likely cause of the recent increase in global atmospheric methane concentration. To improve our understanding of tropical methane sources, we used the eddy covariance technique to measure CH4 flux (FCH4) between a tropical peat forest ecosystem and the atmosphere in Malaysian Borneo over a 2‐month period during the wet season. Mean daily FCH4 during the measurement period, on the order of 0.024 g C‐CH4·m−2·day−1, was similar to eddy covariance FCH4 measurements from tropical rice agroecosystems and boreal fen ecosystems. A linear modeling analysis demonstrated that air temperature (Tair) was critical for modeling FCH4 before the water table breached the surface and that water table alone explained some 20% of observed FCH4 variability once standing water emerged. Future research should measure FCH4 on an annual basis from multiple tropical ecosystems to better constrain tropical biogenic methane sources.
Prediction and Observation of Electron Instabilities and Phase Space Holes Concentrated in the Lunar Plasma Wake
Authors: Hutchinson Ian H. , Malaspina David M.
Published: April 2018

Recent theory and numerical simulation predicts that the wake of the solar wind flow past the Moon should be the site of electrostatic instabilities that give rise to electron holes. These play an important role in the eventual merging of the wake with the background solar wind. Analysis of measurements from the ARTEMIS satellites, orbiting the Moon at distances from 1.2 to 11 RM, detects holes highly concentrated in the wake, in agreement with prediction. The theory also predicts that the hole flux density observed should be hollow, peaking away from the wake axis. Observation statistics qualitatively confirm this hollowness, lending extra supporting evidence for the identification of their generation mechanism.
Global Analysis of Climate Change Projection Effects on Atmospheric Rivers
Authors: Espinoza Vicky , Waliser Duane E. , Guan Bin , Lavers David A. , Ralph F. Martin
Published: April 2018

A uniform, global approach is used to quantify how atmospheric rivers (ARs) change between Coupled Model Intercomparison Project Phase 5 historical simulations and future projections under the Representative Concentration Pathway (RCP) 4.5 and RCP8.5 warming scenarios. The projections indicate that while there will be ~10% fewer ARs in the future, the ARs will be ~25% longer, ~25% wider, and exhibit stronger integrated water vapor transports (IVTs) under RCP8.5. These changes result in pronounced increases in the frequency (IVT strength) of AR conditions under RCP8.5: ~50% (25%) globally, ~50% (20%) in the northern midlatitudes, and ~60% (20%) in the southern midlatitudes. The models exhibit systematic low biases across the midlatitudes in replicating historical AR frequency (~10%), zonal IVT (~15%), and meridional IVT (~25%), with sizable intermodel differences. A more detailed examination of six regions strongly impacted by ARs suggests that the western United States, northwestern Europe, and southwestern South America exhibit considerable intermodel differences in projected changes in ARs.
Atmospheric Gravity Waves in the Ionosphere and Thermosphere During the 2017 Solar Eclipse
Authors: Lin Cissi Y. , Deng Yue , Ridley Aaron
Published: April 2018

As a cavity of solar radiation created by the lunar shadow moves across the United States on 21 August 2017, decreases in local ionospheric and thermospheric (IT) temperature and density are anticipated. The average velocity of the total solar eclipse across the United States is ~700 m/s. The supersonically moving lunar shadow has induced bow waves and gravity waves that are observed by the Global Navigation Satellite System (GNSS) network. We use the Global Ionosphere‐Thermosphere Model, a global circulation model solving for nonhydrostatic equations, with high‐resolution (2° in longitude and 0.5° in latitude) and high‐cadence (forcing updated every 2 s) settings to investigate the IT responses related to the atmospheric gravity wave perturbations during the solar eclipse. The modeled IT conditions extracted at 5‐s cadence at two ground stations reveal different responses in both neutral and electron densities under totality and partial‐eclipse scenarios. A bow wave of −0.2 TECu develops and lasts hours since totality, which is comparable with the GNSS observations. Gravity waves with period of 20–30 min observed by GNSS have been reproduced in our simulations.
Characterization of the Extraterrestrial Magnesium Source in the Atmosphere Using a Meteoric Ablation Simulator
Authors: Bones D. L. , Gómez Martín J. C. , Carrillo Sánchez J. D. , Dobson A. J. , Plane J. M. C.
Published: April 2018

Ablation of Mg from meteoroids entering the Earth's atmosphere was studied experimentally using a Meteoric Ablation Simulator: micron‐sized particles of representative meteoritic material were flash heated to simulate atmospheric entry and the ablation rate of Mg with respect to Na measured by fast time‐resolved laser‐induced fluorescence. Over the range of particle diameters and entry velocities studied, Mg ablates 4.3 ± 2.1 times less efficiently than Na and 2.4 ± 0.8 times less efficiently than Fe. The resulting evaporation profiles indicate that Mg mostly ablates around 84 km in the atmosphere, compared with Fe at 88 km and Na at 95 km. The chemical ablation model Chemical Ablation Model predicts satisfactorily the measured peak ablation altitudes and relative ablated fractions of Mg, Na, Fe, and Ca but does not capture the breadth of the ablation profiles, probably due to the inhomogeneity of the minerals present in meteoroids combined with experimental limitations.
Investigation of Martian Magnetic Topology Response to 2017 September ICME
Authors: Xu Shaosui , Fang Xiaohua , Mitchell David L. , Ma Yingjuan , Luhmann Janet G. , DiBraccio Gina A. , Weber Tristan , Brain David , Mazelle Christian , Curry Shannon M. , Lee Christina O.
Published: April 2018

Many aspects of the Sun‐Mars interaction have been investigated during solar transient events with measurements from multiple spacecrafts and also simulation efforts. Limited discussion has been paid to magnetic topology response to disturbed upstream conditions. The implications of topology changes include, but are not limited to, the pattern of energetic particle precipitation into the Martian atmosphere and the impact on cold ion escape during solar transient events as low‐energy ion escape is dependent on magnetic topology. In this study, we investigate the magnetic topology response to the 2017 September interplanetary coronal mass ejection (ICME) event with measurements collected by the Mars Atmospheric and Volatile EvolutioN spacecraft. It is found that the interface between draped interplanetary magnetic field and closed field lines was moved from 800–1400 km in altitude during quiet conditions to 200–400 km after ICME arrived at Mars and then relaxed back to high altitudes again after the event. To gain insight into magnetic topology response on a global scale, we first validate magnetic topology from a time‐dependent simulation with a single‐fluid multispecies magnetohydrodynamic (MHD) model by comparing magnetic topology determined from Mars Atmospheric and Volatile EvolutioN data, which shows a good agreement. Then we present MHD predictions of global magnetic topology changes during this ICME event. In addition to a deeper interplanetary magnetic field penetration, MHD results suggest more open field lines in response to the ICME event.
Melting Inside the Tibetan Crust? Constraint From Electrical Conductivity of Peraluminous Granitic Melt
Authors: Guo Xuan , Zhang Li , Su Xue , Mao Zhu , Gao Xiao‐Ying , Yang Xiaozhi , Ni Huaiwei
Published: April 2018

Magnetotelluric and seismological studies suggested the presence of partial melts in the middle to lower Himalaya‐Tibetan crust. However, the melt fractions inferred by previous work were based on presumed electrical conductivity of melts. We performed measurements on the electrical conductivity of peraluminous granitic melts with 0.16–8.4 wt % H2O (the expected compositions in the Tibetan crust) at 600–1,300°C and 0.5–1.0 GPa. Peraluminous melt exhibits lower electrical conductivity than peralkaline melt at dry condition, but this difference diminishes at H2O > 2 wt %. With our data, the observed electrical anomalies in the Tibetan crust could be explained by 2–33 vol % of peraluminous granitic melts with H2O > 6 wt %. Possible reasons for our inferred melt fractions being higher than seismological constraints include the following: (1) The real melts are more Na and H2O rich, (2) the effect of melt reducing seismic velocities was overestimated, and (3) the anomalies at some locations are due to fluids.
Assessment of Hydraulic Connectivity of Fractures in Mudstones by Single‐Borehole Investigations
Authors: Ishii Eiichi
Published: April 2018

Assessing the hydraulic connectivity of fractures by single‐borehole investigations is crucial to radioactive waste disposal but is still a challenge as such connectivity is difficult to measure directly. This study presents geological, hydrological, hydrochemical, and rock‐mechanical data for three faulted/fractured mudstones (the Koetoi, Wakkanai, and Palfris Formations) and proposes a new methodology for assessing the hydraulic connectivity of fractures. The methodology consists of three steps: (a) dividing the formation into two domains with a ductility index (DI) of >2 and <2 (DI is defined as the effective mean stress normalized to the tensile strength of intact rock), (b) estimating the hydraulic connectivity of fractures by analyzing pressure change obtained by packer tests and geological interpretation, and (c) verifying the estimation using pore pressure and water chemistry/geochemistry. The first step is necessary because the failure mode of damage‐zone fractures in fault zones can differ between the DI > 2 and DI < 2 domains, which may lead to significant differences in the hydraulic connectivity of fractures. During the second step, potential domains in which the hydraulic connectivity of fractures is limited are identified where upward trends, characterized by slopes of ∼0.5–1.0, are observed during the middle to late period of elapsed time on log‐log plots of pressure derivatives. Although the third step can be performed in various ways, this study employs the observation of pressure anomalies and the detection of young external water. Analyses of the three formations demonstrate the applicability and reliability of the proposed methodology.
TRPM2: a candidate therapeutic target for treating neurological diseases
Authors: Belrose Jillian Corinne , Jackson Michael Frederick
Published: April 2018

Transient receptor potential melastatin 2 (TRPM2) is a calcium (Ca2+)-permeable non-selective cation channel belonging to the TRP ion channel family. Oxidative stress-induced TRPM2 activation provokes aberrant intracellular Ca2+ accumulation and cell death in a variety of cell types, including neurons. Aberrant TRPM2 function has been implicated in several neurological disorders including ischemia/stroke, Alzheimer's disease, neuropathic pain, Parkinson's disease and bipolar disorder. In addition to research identifying a role for TRPM2 in disease, progress has been made in the identification of physiological functions of TRPM2 in the brain, including recent evidence that TRPM2 is necessary for the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression, an important form of synaptic plasticity at glutamate synapses. Here, we summarize recent evidence on the role of TRPM2 in the central nervous system (CNS) in health and disease and discuss the potential therapeutic implications of targeting TRPM2. Collectively, these studies suggest that TRPM2 represents a prospective novel therapeutic target for neurological disorders.
Upregulation of SALL4 by EGFR activation regulates the stemness of CD44-positive lung cancer
Authors: Du Wenjing , Ni Lan , Liu Baojun , Wei Ying , Lv Yubao , Qiang Sujing , Dong Jingcheng , Liu Xijun
Published: April 2018

The transcriptional factor SALL4, an important stem cell regulator, is expressed in hematopoietic stem cells and various malignancies, but its role in EGFR-mutated NSCLCs has not been studied yet. Here, we report that the expression of Sal-like protein 4 (SALL4), was significantly higher in EGFR mutated lung tumors than in non-tumor tissue. SALL4-high lung cancer patients had poorer prognosis after surgery than SALL4-low patients. The expression of SALL4 could be induced by the activation of EGFR through the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. The knockdown of SALL4 expression could suppress spheroid formation and the expression of lung cancer stem cell marker CD44. More interestingly, the knockdown of SALL4 expression could suppress the migration, invasion, and metastasis of the lung cancer cells and significantly increase the sensitivity of EGFR mutated cells to Erlotinib. These results suggest that SALL4 may be a novel potential therapeutic target for the diagnosis and treatment of lung cancer.
Structural basis for GPR40 allosteric agonism and incretin stimulation
Authors: Ho Joseph D. , Chau Betty , Rodgers Logan , Lu Frances , Wilbur Kelly L. , Otto Keith A. , Chen Yanyun , Song Min , Riley Jonathan P. , Yang Hsiu-Chiung , Reynolds Nichole A. , Kahl Steven D. , Lewis Anjana Patel , Groshong Christopher , Madsen Russell E. , Conners Kris , Lineswala Jayana P. , Gheyi Tarun , Saflor Melbert-Brian Decipulo , Lee Matthew R. , Benach Jordi , Baker Kenton A. , Montrose-Rafizadeh Chahrzad , Genin Michael J. , Miller Anne R. , Hamdouchi Chafiq
Published: April 2018

Activation of free fatty acid receptor 1 (GPR40) by synthetic partial and full agonists occur via distinct allosteric sites. A crystal structure of GPR40-TAK-875 complex revealed the allosteric site for the partial agonist. Here we report the 2.76-Å crystal structure of human GPR40 in complex with a synthetic full agonist, compound 1, bound to the second allosteric site. Unlike TAK-875, which acts as a Gαq-coupled partial agonist, compound 1 is a dual Gαq and Gαs-coupled full agonist. compound 1 binds in the lipid-rich region of the receptor near intracellular loop 2 (ICL2), in which the stabilization of ICL2 by the ligand is likely the primary mechanism for the enhanced G protein activities. The endogenous free fatty acid (FFA), γ-linolenic acid, can be computationally modeled in this site. Both γ-linolenic acid and compound 1 exhibit positive cooperativity with TAK-875, suggesting that this site could also serve as a FFA binding site.
Regulation of Yki/Yap subcellular localization and Hpo signaling by a nuclear kinase PRP4K
Authors: Cho Yong suk , Zhu Jian , Li Shuangxi , Wang Bing , Han Yuhong , Jiang Jin
Published: April 2018

Hippo (Hpo) signaling pathway controls tissue growth by regulating the subcellular localization of Yorkie (Yki)/Yap via a cytoplasmic kinase cassette containing an upstream kinase Hpo/MST1/2 and a downstream kinase Warts (Wts)/Lats1/2. Here we show that PRP4K, a kinase involved in mRNA splicing, phosphorylates Yki/Yap in the nucleus to prevent its nuclear accumulation and restrict Hpo pathway target gene expression. PRP4K inactivation accelerates whereas excessive PRP4K inhibits Yki-driven tissue overgrowth. PRP4K phosphorylates a subset of Wts/Lats1/2 sites on Yki/Yap to inhibit the binding of Yki/Yap to the Scalloped (Sd)/TEAD transcription factor and exclude Yki/Yap nuclear localization depending on nuclear export. Furthermore, PRP4K inhibits proliferation and invasiveness of cultured breast cancer cells and its high expression correlates with good prognosis in breast cancer patients. Our study unravels an unanticipated layer of Hpo pathway regulation and suggests that PRP4K-mediated Yki/Yap phosphorylation in the nucleus provides a fail-safe mechanism to restrict aberrant pathway activation.
Long-term viability and function of transplanted islets macroencapsulated at high density are achieved by enhanced oxygen supply
Authors: Evron Yoav , Colton Clark K. , Ludwig Barbara , Weir Gordon C. , Zimermann Baruch , Maimon Shiri , Neufeld Tova , Shalev Nurit , Goldman Tali , Leon Assaf , Yavriyants Karina , Shabtay Noa , Rozenshtein Tania , Azarov Dimitri , DiIenno Amanda R. , Steffen Anja , de Vos Paul , Bornstein Stefan R. , Barkai Uriel , Rotem Avi
Published: April 2018

Transplantation of encapsulated islets can cure diabetes without immunosuppression, but oxygen supply limitations can cause failure. We investigated a retrievable macroencapsulation device wherein islets are encapsulated in a planar alginate slab and supplied with exogenous oxygen from a replenishable gas chamber. Translation to clinically-useful devices entails reduction of device size by increasing islet surface density, which requires increased gas chamber pO2. Here we show that islet surface density can be substantially increased safely by increasing gas chamber pO2 to a supraphysiological level that maintains all islets viable and functional. These levels were determined from measurements of pO2 profiles in islet-alginate slabs. Encapsulated islets implanted with surface density as high as 4,800 islet equivalents/cm3 in diabetic rats maintained normoglycemia for more than 7 months and provided near-normal intravenous glucose tolerance tests. Nearly 90% of the original viable tissue was recovered after device explantation. Damaged islets failed after progressively shorter times. The required values of gas chamber pO2 were predictable from a mathematical model of oxygen consumption and diffusion in the device. These results demonstrate feasibility of developing retrievable macroencapsulated devices small enough for clinical use and provide a firm basis for design of devices for testing in large animals and humans.