bluuebunny/crossref_metadata_2025 huggingface dataset:
Some explicit results on one kind of sticky diffusion
Authors: Jiang Yiming , Song Shiyu , Wang Yongjin
Published: July 2019

In this paper we derive several explicit results on one special sticky diffusion process which is constructed as a time-changed version of a diffusion with no sticky points. A theorem concerning the process-related Green operators defined on some nonnegative piecewise continuous functions is provided. Then, based on this theorem, we explore the distributional properties of the sticky diffusion. A financial application is presented where we compute the value of the European vanilla call option written on the underlying with sticky price dynamics.
Measures of ageing tendency
Authors: Szymkowiak Magdalena
Published: July 2019

A family of generalized ageing intensity functions of univariate absolutely continuous lifetime random variables is introduced and studied. They allow the analysis and measurement of the ageing tendency from various points of view. Some of these generalized ageing intensities characterize families of distributions dependent on a single parameter, while others determine distributions uniquely. In particular, it is shown that the elasticity functions of various transformations of distributions that appear in lifetime analysis and reliability theory uniquely characterize the parent distribution. Moreover, the recognition of the shape of a properly chosen generalized ageing intensity estimate admits a simple identification of the data lifetime distribution.
Gesture in contexts of scopal ambiguity: Negation and quantification in English
Authors: Brown Amanda , Kamiya Masaaki
Published: July 2019

Gestures can play a facilitative role in the interpretation of structural ambiguities (Guellaiï, Langus, & Nespor, 2014; Prieto, Borràs-Comes, Tubau, & Espinal, 2013; Tubau, González-Fuente, Prieto, & Espinal, 2015) and are associated with spoken expression of negation (Calbris, 2011; Harrison, 2014a; Kendon, 2002, 2004). This study examines gestural forms and timing patterns with specific interpretations intended by speakers in a context of negation in English where the presence of quantification (all/most/many) yields scope ambiguities, for example,All the students didn’t go= (1). Some number of the students went, but all is not the correct number (negation takes wide scope over the quantifier;not>all), versus (2) some number of the students didn’t go, and all is that number (negation takes narrow scope over the quantifier,all>not; see Horn, 2001, Jackendoff, 1972; Syrett, Simon, & Nisula, 2014b). Twenty-five native English speakers produced scopally ambiguous sentences. Analyses of 317 co-occurring gestures revealed a preponderance of head gestures and use of semantically congruent head shakes, alignment of gestures with the negator, and lengthening of gesture strokes where interpretations involved narrow-scope negation. Results are discussed with reference to scope of negation and gesture (Harrison, 2010, 2013, 2014a, 2014b) particularly in comparison to variable patterns found for prosody (Syrett, Simon, & Nisula, 2014a).
On the residual and profinite closures of commensurated subgroups
Authors: CAPRACE PIERRE–EMMANUEL , KROPHOLLER PETER H. , REID COLIN D. , WESOLEK PHILLIP
Published: July 2019

The residual closure of a subgroup H of a group G is the intersection of all virtually normal subgroups of G containing H. We show that if G is generated by finitely many cosets of H and if H is commensurated, then the residual closure of H in G is virtually normal. This implies that separable commensurated subgroups of finitely generated groups are virtually normal. A stream of applications to separable subgroups, polycyclic groups, residually finite groups, groups acting on trees, lattices in products of trees and just-infinite groups then flows from this main result.
Does Obstructive Sleep Apnea Increase Cognitive Deficits in Pediatric Sickle Cell Disease?
Authors: Bills Sarah E. , Katz Tal , McNeil Jaleel , Schatz Jeffrey
Published: July 2019

Objectives: Although pediatric obstructive sleep apnea (OSA) is estimated to affect 2–3% of the general population, its prevalence in sickle cell disease (SCD) is much higher, with research suggesting a prevalence rate of upwards of 40%. Despite the similar underlying pathophysiological mechanisms of neurocognitive effects in pediatric OSA and SCD, there is a scarcity of information on how these two conditions interact. The aim of this study was to better understand the contribution of sleep apnea to neurocognitive deficits in children diagnosed with SCD. Method: This study assessed cognitive function in 26 children with comorbid SCD and OSA, 39 matched comparisons with SCD only, and 59 matched comparisons in children without a chronic health condition. Results: There were significant differences on measures of processing speed and reading decoding, with children without a chronic health condition scoring better than both chronic health condition groups. Additionally, the no chronic health condition group performed better on a test of quantitative knowledge and reasoning and a test of visual–spatial construction than the SCD-only group. Contrary to our hypotheses, there were no between-group differences suggesting an additive impact of OSA on cognition. Exploratory analyses revealed associations within the group that had OSA showing that more severe OSA correlated with lower performance on measures of processing speed and quantitative knowledge/reasoning. Conclusions: Children with comorbid OSA and SCD do not present with greater deficits in cognitive functioning than children with SCD alone. However, severe OSA may confer additional risk for neurocognitive impairments.
The Washington State Twin Registry: 2019 Update
Authors: Duncan Glen E. , Avery Ally R. , Strachan Eric , Turkheimer Eric , Tsang Siny
Published: July 2019

It has been over 5 years since the last special issue ofTwin Research and Human Geneticson ‘Twin Registries Worldwide: An Important Resource for Scientific Research’ was published. Much progress has been made in the broad field of twin research since that time, and the current special issue is a follow-up to update the scientific community about twin registries around the globe. The present article builds upon our 2013 Registry description by summarizing current information on the Washington State Twin Registry (WSTR), including history and construction methods, member characteristics, available data, and major research goals. We also provide a section with brief summaries of recently completed studies and discuss the future research directions of the WSTR. The Registry has grown in terms of size and scope since 2013; highlights include recruitment of youth pairs under 18 years of age, extensive geocoding work to develop environmental exposures that can be linked to survey and administrative health data such as death records, and expansion of a biobank with specimens collected for genotyping, DNA methylation, and microbiome based-studies.
Schülerinnen und Schüler mit sonderpädagogischem Förderbedarf im Bereich emotionale und soziale Entwicklung und ihre Peers im inklusiven Unterricht
Authors: Crede Julia , Wirthwein Linda , Steinmayr Ricarda , Bergold Sebastian
Published: July 2019

Zusammenfassung. In der vorliegenden Untersuchung wurde der Frage nachgegangen, ob sich Schülerinnen und Schüler mit dem sonderpädagogischen Förderbedarf im Bereich emotionale und soziale Entwicklung (SPF ESE) im inklusiven Unterrichtssetting in der sozialen Partizipation, in der Schuleinstellung sowie im schulischen Selbstkonzept von ihren Mitschülerinnen und Mitschülern ohne SPF unterscheiden. An einer Stichprobe von N = 872 Schülerinnen und Schülern (davon n >= 38 Schülerinnen und Schüler mit SPF ESE) der 2. und 3. Klassen wurde der Fragebogen zur Erfassung der emotionalen und sozialen Schulerfahrungen (FEESS 3 – 4; 62-1 Rauer & Schuck, 2003) mit den Skalen soziale Integration, Klassenklima, Gefühl des Angenommenseins, Schuleinstellung und Selbstkonzept der Schulfähigkeit erhoben. Verglichen mit einer durch Propensity Score Matching gebildeten Kontrollgruppe wiesen Schülerinnen und Schüler mit SPF ESE signifikant negativere Werte in den Bereichen soziale Integration, Klassenklima und schulischem Selbstkonzept auf. Die Ergebnisse werden in Bezug auf die Notwendigkeit der spezifischen Betrachtung bestimmter Förderschwerpunkte und vor dem Hintergrund der Ziele inklusiven Unterrichts im sozial-emotionalen Bereich diskutiert.
Explosive Eruptions With Little Warning: Experimental Petrology and Volcano Monitoring Observations From the 2014 Eruption of Kelud, Indonesia
Authors: Cassidy M. , Ebmeier S. K. , Helo C. , Watt S. F. L. , Caudron C. , Odell A. , Spaans K. , Kristianto P. , Triastuty H. , Gunawan H. , Castro J. M.
Published: July 2019

Explosive eruptions that occur with little or no precursory unrest (less than a month) pose the greatest hazards from volcanoes to nearby populations. Here we focus on the preeruptive conditions for these explosive events, their triggers and how these eruptions evolve. We concentrate on Kelud volcano, where we have conducted a set of petrological experiments to understand preeruptive storage conditions for several recent eruptions. For the 2014 explosive eruption, we combine this with an analysis of interferometric synthetic aperture radar measured deformation. Our data suggest that both explosive and effusive eruptions at Kelud are sourced from a magma storage system at 2–4 km. However, explosive eruptions are fed by magma stored under relatively cool (~1000 °C) and water‐saturated conditions, whereas effusive eruptions are fed by slightly hotter (~1050 °C), water‐undersaturated magmas. We propose that the initial phase of the 2014 eruption was triggered by volatile overpressure, which then fostered top‐down decompression tapping discrete magma bodies. By compiling a global data set of monitoring signatures of explosive eruptions, we show that the onset of unrest rarely points to the shallow ascent of magma to the surface, as ascent mostly occurs in a matter of hours or minutes. We relate the timescale of preeruptive unrest to eruption triggering mechanisms, with yearly/decadal periods of unrest relating to magma injection events (which may or may not precede a magmatic eruption), whereas internal triggering (e.g., second boiling) of an already present, cooling magma body can lead to explosive eruptions with little warning.
Assessment of Storm Wind Speed Prediction Using Gridded Bayesian Regression Applied to Historical Events With NCAR's Real‐Time Ensemble Forecast System
Authors: Yang Jaemo , Astitha Marina , Schwartz Craig S.
Published: July 2019

This study presents the development and application of gridded Bayesian linear regression (GBLR) as a new statistical postprocessing technique to improve deterministic numerical weather prediction of storm wind speed forecasts over the northeast United States. GBLR products are produced by interpolating regression coefficients deduced from modeled‐observed pairs of historical storms at meteorological stations to grid points, thus producing a gridded product. The GBLR model is developed for the 10 members of the National Center for Atmospheric Research (NCAR) real‐time dynamic ensemble prediction system for a database composed of 92 storms, using leave‐one‐storm‐out cross validation. GBLR almost eliminates the bias of the raw deterministic prediction and achieves average coefficient of determination (R2) improvement of 36% and root‐mean‐square error reduction of 29% with respect to the ensemble mean for individual storm forecasts. Moreover, verification using leave‐one‐station‐out cross validation indicates that the GBLR model provides acceptable forecast improvements for grid points where no observations are available. The GBLR technique contributes to improving gridded storm wind speed forecasts using past event‐based data and has the potential to be implemented in real time.
E3SMv0‐HiLAT: A Modified Climate System Model Targeted for the Study of High‐Latitude Processes
Authors: Hecht Matthew , Veneziani Milena , Weijer Wilbert , Kravitz Ben , Burrows Susannah , Comeau Darin , Hunke Elizabeth , Jeffery Nicole , Urrego‐Blanco Jorge , Wang Hailong , Wang Shanlin , Zhang Jiaxu , Bailey David , Mills Catrin , Rasch Philip , Urban Nathan
Published: July 2019

We document the configuration, tuning, and evaluation of a modified version of the Community Earth System Model version 1 (Hurrell et al., 2013, https://doi.org/10.1175/BAMS-D-12), introduced here as E3SMv0‐HiLAT, intended for study of high‐latitude processes. E3SMv0‐HiLAT incorporates changes to the atmospheric model affecting aerosol transport to high northern latitudes and to reduce shortwave cloud bias over the Southern Ocean. An updated sea ice model includes biogeochemistry that is coupled to an extended version of the ocean model's biogechemistry. This enables cloud nucleation to depend on the changing marine emissions of aerosol precursors, which may be expected in scenarios with strongly changing sea ice extent, oceanic stratification and associated nutrient availability, and atmospheric state. An evaluation of the basic preindustrial state of E3SMv0‐HiLAT is presented in order to ensure that its climate is adequate to support future experimentation. Additional capability is not achieved without some cost, relative to the extraordinarily well‐tuned model from which it was derived. In particular, a reduction of bias in cloud forcing achieved over the Southern Hemisphere also allows for greater Southern Ocean sea ice extent, a tendency that has been partially but not fully alleviated through experimentation and tuning. The most interesting change in the behavior of the model may be its response to greenhouse gas forcing: While the climate sensitivity is found to be essentially unchanged from that of Community Earth System Model version 1, the adjusted radiative forcing has increased from within one standard deviation above that of Coupled Model Intercomparison Project Phase 5 models to nearly two standard deviations.
A New Signal of the Solar Magnetic Cycle: Opposite Shifts of Weak Magnetic Field Distributions in the Two Hemispheres
Authors: Getachew Tibebu , Virtanen Ilpo , Mursula Kalevi
Published: July 2019

We study the asymmetric distribution of weak photospheric magnetic field values in the two hemispheres separately using synoptic maps from Solar Dynamics Observatory/Helioseismic and Magnetic Imager, Synoptic Optical Long‐term Investigations of the Sun/Vector SpectroMagnetograph, and Wilcox Solar Observatory during Solar Cycles 21–24. We calculate the weak‐field asymmetry (shift) by fitting the distributions of weak‐field values to a shifted Gaussian. Hemispheric shifts derived from the three data sets agree very well and increase systematically when reducing the spatial resolution of the map. Shifts of the Northern and Southern Hemispheres are typically opposite to each other. Shifts follow the evolution of the trailing flux and have a strong solar cycle variation with maxima in the early to mid declining phase of the solar cycle. The sign of the hemispheric weak‐field shift is always the same as the polarity of the polar field in the respective hemisphere and solar cycle. We also find that shifts in the south are systematically larger in absolute value than in the north.
Pervasive Foreshock Activity Across Southern California
Authors: Trugman Daniel T. , Ross Zachary E.
Published: July 2019

Foreshocks have been documented as preceding less than half of all mainshock earthquakes. These observations are difficult to reconcile with laboratory earthquake experiments and theoretical models of earthquake nucleation, which both suggest that foreshock activity should be nearly ubiquitous. Here we use a state‐of‐the‐art, high‐resolution earthquake catalog to study foreshock sequences of magnitude M4 and greater mainshocks in southern California from 2008–2017. This highly complete catalog provides a new opportunity to examine smaller magnitude precursory seismicity. Seventy‐two percent of mainshocks within this catalog are preceded by foreshock activity that is significantly elevated compared to the local background seismicity rate. Foreshock sequences vary in duration from several days to weeks, with a median of 16.6 days. The results suggest that foreshock occurrence in nature is more prevalent than previously thought and that our understanding of earthquake nucleation may improve in tandem with advances in our ability to detect small earthquakes.
Ecohydrology Controls the Geomorphic Response to Climate Change
Authors: Yetemen Omer , Saco Patricia M. , Istanbulluoglu Erkan
Published: July 2019

Erosion rate data worldwide show complex and contrasting dependencies to climate. Laboratory and numerical model experiments on abiotic landscapes suggest a positive response: Wetter (drier) shift in climate leads to an increase (decrease) in erosion rates with longer relaxation times under a drier climate. We performed eco‐geomorphic landscape evolution model simulations driven by abrupt climate shift in a semiarid climate. With dynamic vegetation, the erosional response to climate shift was opposite to bare soil, variability of erosion rate lessened, and landscape relaxation time scales became insensitive to climate change direction. The spatial geomorphic response to a wetter climate was depositional in vegetated, incisional in barren landscapes, and got reversed with drier climate. A relationship between net erosion rate and mean landscape slope emerged, exhibiting a hysteresis loop. Our study offers insights to the interpretation of observed acceleration of erosion rates and increase mountain relief during Quaternary climate change.
Contributions of aerosol‐cloud interactions to mid‐Piacenzian seasonally sea ice‐free Arctic Ocean
Authors: Feng Ran , Otto‐Bliesner Bette L. , Xu Yangyang , Brady Esther , Fletcher Tamara , Ballantyne Ashley
Published: July 2019

Forcings and feedbacks controlling the seasonally sea ice‐free Arctic Ocean during the mid‐Piacenzian Warm period (3.264–3.025 Ma, MPWP), a period when CO2 level, geography, and topography were similar to present day, remain unclear given that many complex Earth System Models with comparatively higher skills at simulating twentieth century Arctic sea ice tend to produce perennial Arctic sea ice for this period. We demonstrate that explicitly simulating aerosol‐cloud interactions and the exclusion of industrial pollutants from model forcing conditions is key to simulating seasonally sea ice‐free Arctic Ocean of MPWP. The absence of industrial pollutants leads to fewer and larger cloud droplets over the high‐latitude Northern Europe and North Pacific, which allows greater absorption of solar radiation at the surface during the early summer. This enhanced absorption triggers the seasonally runaway sea ice surface albedo feedback that gives rise to September sea ice‐free Arctic Ocean and strongly amplified northern high‐latitude surface warmth.
Beyond the Minisolar Maximum of Solar Cycle 24: Declining Solar Magnetic Fields and the Response of the Terrestrial Magnetosphere
Authors: Ingale M. , Janardhan P. , Bisoi S. K.
Published: July 2019

The present study examines the response of the terrestrial magnetosphere to the long‐term steady declining trends observed in solar magnetic fields and solar wind microturbulence levels since mid‐1990s that has been continuing beyond the minisolar maximum of cycle 24. A detailed analysis of the response of the terrestrial magnetosphere has been carried out by studying the extent and shape of the Earth's magnetopause and bow shock over the past four solar cycles. We estimate subsolar stand‐off distance of the magnetopause and bow shock and the shape of the magnetopause, using numerical as well as empirical models. The computed magnetopause and bow shock stand‐off distances have been found to be increasing steadily since around mid‐1990s, consistent with the steady declining trend seen in solar magnetic fields and solar wind microturbulence levels. Similarly, we find an expansion in the shape of the magnetopause since 1996. The implications of the increasing trend seen in the magnetopause and bow shock stand‐off distances are discussed and a forecast of the shape of the magnetopause in 2020, the minimum of cycle 24, has been made. Importantly, we also find two instances between 1968 and 1991 when the magnetopause stand‐off distance dropped to values close to 6.6 Earth radii, the geostationary orbit, for duration ranging from 9–11 hr and one event in 2005, post 1995 when the decline in photospheric fields began. Though there have been no such events since 2005, it represents a clear and present danger to our satellite systems.
Surface Water Body Detection in Polarimetric SAR Data Using Contextual Complex Wishart Classification
Authors: Goumehei E. , Tolpekin V. , Stein A. , Yan W.
Published: July 2019

Detection of surface water from satellite images is important for water management purposes like for mapping flood extents, inundation dynamics, and water resources distributions. In this research, we introduce a supervised contextual classification model to detect surface water bodies from polarimetric Synthetic Aperture Radar (SAR) data. A complex Wishart Markov Random Field (WMRF) combines Markov Random Fields with the complex Wishart distribution. It is applied on Single Look Complex Sentinel 1 data. Using Markov Random Fields, we utilize the geometry of surface water to remove speckle from SAR images. Results were compared with the Wishart Maximum Likelihood Classification (WMLC), the Gaussian Maximum Likelihood Classification, and a median filter followed by thresholding. Experiments demonstrate that the statistical representation of data using the Wishart distribution improves the F‐score to 0.95 for WMRF, while it is 0.67, 0.88, and 0.91 for Gaussian Maximum Likelihood Classification, WMLC, and thresholding, respectively. The main improvement in the precision increases from 0.80 and 0.86 for WMLC and thresholding to 0.96 for WMRF. The WMRF model accurately distinguishes classes that have a similar backscatter, like water and bare soil. Hence, the high accuracy of the proposed WMRF model is a result of its robustness for water detection from Single Look Complex data. We conclude that the proposed model is a great improvement on existing methods for the detection of calm surface water bodies.
Real-time decoding of question-and-answer speech dialogue using human cortical activity
Authors: Moses David A. , Leonard Matthew K. , Makin Joseph G. , Chang Edward F.
Published: July 2019

Natural communication often occurs in dialogue, differentially engaging auditory and sensorimotor brain regions during listening and speaking. However, previous attempts to decode speech directly from the human brain typically consider listening or speaking tasks in isolation. Here, human participants listened to questions and responded aloud with answers while we used high-density electrocorticography (ECoG) recordings to detect when they heard or said an utterance and to then decode the utterance’s identity. Because certain answers were only plausible responses to certain questions, we could dynamically update the prior probabilities of each answer using the decoded question likelihoods as context. We decode produced and perceived utterances with accuracy rates as high as 61% and 76%, respectively (chance is 7% and 20%). Contextual integration of decoded question likelihoods significantly improves answer decoding. These results demonstrate real-time decoding of speech in an interactive, conversational setting, which has important implications for patients who are unable to communicate.
m6A modification of a 3′ UTR site reduces RME1 mRNA levels to promote meiosis
Authors: Bushkin G. Guy , Pincus David , Morgan Jeffrey T. , Richardson Kris , Lewis Caroline , Chan Sze Ham , Bartel David P. , Fink Gerald R.
Published: July 2019

Despite the vast number of modification sites mapped within mRNAs, known examples of consequential mRNA modifications remain rare. Here, we provide multiple lines of evidence to show that Ime4p, an N6-methyladenosine (m6A) methyltransferase required for meiosis in yeast, acts by methylating a site in the 3′ UTR of the mRNA encoding Rme1p, a transcriptional repressor of meiosis. Consistent with this mechanism, genetic analyses reveal that IME4 functions upstream of RME1. Transcriptome-wide, RME1 is the primary message that displays both increased methylation and reduced expression in an Ime4p-dependent manner. In yeast strains for which IME4 is dispensable for meiosis, a natural polymorphism in the RME1 promoter reduces RME1 transcription, obviating the requirement for methylation. Mutation of a single m6A site in the RME1 3′ UTR increases Rme1p repressor production and reduces meiotic efficiency. These results reveal the molecular and physiological consequences of a modification in the 3′ UTR of an mRNA.
Detailed modeling of positive selection improves detection of cancer driver genes
Authors: Zhao Siming , Liu Jun , Nanga Pranav , Liu Yuwen , Cicek A. Ercument , Knoblauch Nicholas , He Chuan , Stephens Matthew , He Xin
Published: July 2019

Identifying driver genes from somatic mutations is a central problem in cancer biology. Existing methods, however, either lack explicit statistical models, or use models based on simplistic assumptions. Here, we present driverMAPS (Model-based Analysis of Positive Selection), a model-based approach to driver gene identification. This method explicitly models positive selection at the single-base level, as well as highly heterogeneous background mutational processes. In particular, the selection model captures elevated mutation rates in functionally important sites using multiple external annotations, and spatial clustering of mutations. Simulations under realistic evolutionary models demonstrate the increased power of driverMAPS over current approaches. Applying driverMAPS to TCGA data of 20 tumor types, we identified 159 new potential driver genes, including the mRNA methyltransferase METTL3-METTL14. We experimentally validated METTL3 as a tumor suppressor gene in bladder cancer, providing support to the important role mRNA modification plays in tumorigenesis.
Disentangling molecular alterations from water-content changes in the aging human brain using quantitative MRI
Authors: Filo Shir , Shtangel Oshrat , Salamon Noga , Kol Adi , Weisinger Batsheva , Shifman Sagiv , Mezer Aviv A.
Published: July 2019

It is an open question whether aging-related changes throughout the brain are driven by a common factor or result from several distinct molecular mechanisms. Quantitative magnetic resonance imaging (qMRI) provides biophysical parametric measurements allowing for non-invasive mapping of the aging human brain. However, qMRI measurements change in response to both molecular composition and water content. Here, we present a tissue relaxivity approach that disentangles these two tissue components and decodes molecular information from the MRI signal. Our approach enables us to reveal the molecular composition of lipid samples and predict lipidomics measurements of the brain. It produces unique molecular signatures across the brain, which are correlated with specific gene-expression profiles. We uncover region-specific molecular changes associated with brain aging. These changes are independent from other MRI aging markers. Our approach opens the door to a quantitative characterization of the biological sources for aging, that until now was possible only post-mortem.
Clostridium perfringens epsilon toxin vaccine candidate lacking toxicity to cells expressing myelin and lymphocyte protein
Authors: Morcrette Helen , Bokori-Brown Monika , Ong Stephanie , Bennett Leo , Wren Brendan W. , Lewis Nick , Titball Richard W.
Published: July 2019

A variant form of Clostridium perfringens epsilon toxin (Y30A-Y196A) with mutations, which shows reduced binding to Madin–Darby canine kidney (MDCK) cells and reduced toxicity in mice, has been proposed as the next-generation enterotoxaemia vaccine. Here we show that, unexpectedly, the Y30A-Y196A variant does not show a reduction in toxicity towards Chinese hamster ovary (CHO) cells engineered to express the putative receptor for the toxin (myelin and lymphocyte protein; MAL). The further addition of mutations to residues in a second putative receptor binding site of the Y30A-Y196A variant further reduces toxicity, and we selected Y30A-Y196A-A168F for further study. Compared to Y30A-Y196A, Y30A-Y196A-A168F showed more than a 3-fold reduction in toxicity towards MDCK cells, more than a 4-fold reduction in toxicity towards mice and at least 200-fold reduction in toxicity towards CHO cells expressing sheep MAL. The immunisation of rabbits or sheep with Y30A-Y196A-A168F induced high levels of neutralising antibodies against epsilon toxin, which persisted for at least 1 year. Y30A-Y196A-A168F is a candidate for development as a next-generation enterotoxaemia vaccine.
Opportunistic complexes of E. coli L-asparaginases with citrate anions
Authors: Lubkowski Jacek , Chan Waikin , Wlodawer Alexander
Published: July 2019

Active sites of enzymes are highly optimized for interactions with specific substrates, thus binding of opportunistic ligands is usually observed only in the absence of native substrates or products. However, during growth of crystals required for structure determination enzymes are often exposed to conditions significantly divergent from the native ones, leading to binding of unexpected ligands to active sites even in the presence of substrates. Failing to recognize this possibility may lead to incorrect interpretation of experimental results and to faulty conclusions. Here, we present several examples of binding of a citrate anion to the active sites of E. coli L-asparaginases I and II, even in the presence of the native substrate, L-Asn. A part of this report focuses on a comprehensive re-interpretation of structural results published previously for complexes of type I L-asparaginase (EcAI) from E. coli. In two re-refined structures a citrate anion forms an acyl-enzyme reaction intermediate with the catalytic threonine. These results emphasize the importance of careful and critical analysis during interpretation of crystallographic data.
Endogenous IQGAP1 and IQGAP3 do not functionally interact with Ras
Authors: Morgan Chase J. , Hedman Andrew C. , Li Zhigang , Sacks David B.
Published: July 2019

The Ras family of small GTPases modulates numerous essential processes. Activating Ras mutations result in hyper-activation of selected signaling cascades, which leads to human diseases. The high frequency of Ras mutations in human malignant neoplasms has led to Ras being a desirable chemotherapeutic target. The IQGAP family of scaffold proteins binds to and regulates multiple signaling molecules, including the Rho family GTPases Rac1 and Cdc42. There are conflicting data in the published literature regarding interactions between IQGAP and Ras proteins. Initial reports showed no binding, but subsequent studies claim associations of IQGAP1 and IQGAP3 with K-Ras and H-Ras, respectively. Therefore, we set out to resolve this controversy. Here we demonstrate that neither endogenous IQGAP1 nor endogenous IQGAP3 binds to the major Ras isoforms, namely H-, K-, and N-Ras. Importantly, Ras activation by epidermal growth factor is not altered when IQGAP1 or IQGAP3 proteins are depleted from cells. These data strongly suggest that IQGAP proteins are not functional interactors of H-, K-, or N-Ras and challenge the rationale for targeting the interaction of Ras with IQGAP for the development of therapeutic agents.
The relationship between pubertal timing and markers of vascular and cardiac structure and function in men and women aged 60–64 years
Authors: Hardy Rebecca , Maddock Jane , Ghosh Arjun K. , Hughes Alun D. , Kuh Diana
Published: July 2019

Earlier age at menarche has been associated with higher risk of coronary heart disease, but the mechanisms underlying the association remain unclear. We assessed the relationship of pubertal timing, in both men (n = 672) and women (n = 713), with vascular (carotid intima-media thickness (cIMT), pulse wave velocity (PWV)) and cardiac (left ventricular (LV) structure and function) measures recorded at age 60–64 yrs in a British birth cohort study. Regression models found that earlier menarche was associated with higher (more adverse) LV mass, LV end diastolic volume and left atrial volume, but not with other cardiac measures, cIMT or PWV. Associations were attenuated after adjustment for either adult or childhood BMI (e.g. mean difference in LV mass per year later menarche: −4.2 g (95% CI:−7.0,−1.4) reducing to −2.2 g (95% CI:−4.7,0.4) after adjustment for adult BMI). There were no associations among men, despite those fully mature at 15 yrs having higher blood pressure than the least mature group by 10.21 mmHg (95% CI:19.45,0.98). Any effect of pubertal timing on vascular and cardiac structure and function is likely to be small and primarily confounded by pre-pubertal BMI and/or mediated through adult adiposity.
Healthy ageing trajectories and lifestyle behaviour: the Mexican Health and Aging Study
Authors: Daskalopoulou Christina , Koukounari Artemis , Wu Yu-Tzu , Terrera Graciela Muniz , Caballero Francisco Félix , de la Fuente Javier , Tyrovolas Stefanos , Panagiotakos Demosthenes B. , Prince Martin , Prina Matthew
Published: July 2019

Projections show that the number of people above 60 years old will triple by 2050 in Mexico. Nevertheless, ageing is characterised by great variability in the health status. In this study, we aimed to identify trajectories of health and their associations with lifestyle factors in a national representative cohort study of older Mexicans. We used secondary data of 14,143 adults from the Mexican Health and Aging Study (MHAS). A metric of health, based on the conceptual framework of functional ability, was mapped onto four waves (2001, 2003, 2012, 2015) and created by applying Bayesian multilevel Item Response Theory (IRT). Conditional Growth Mixture Modelling (GMM) was used to identify latent classes of individuals with similar trajectories and examine the impact of physical activity, smoking and alcohol on those. Conditional on sociodemographic and lifestyle behaviour four latent classes were suggested: high-stable, moderate-stable, low-stable and decliners. Participants who did not engage in physical activity, were current or previous smokers and did not consume alcohol at baseline were more likely to be in the trajectory with the highest deterioration (i.e. decliners). This study confirms ageing heterogeneity and the positive influence of a healthy lifestyle. These results provide the ground for new policies.
Travel linearity and speed of human foragers and chimpanzees during their daily search for food in tropical rainforests
Authors: Jang Haneul , Boesch Christophe , Mundry Roger , Ban Simone D. , Janmaat Karline R. L.
Published: July 2019

To understand the evolutionary roots of human spatial cognition, researchers have compared spatial abilities of humans and one of our closest living relatives, the chimpanzee (Pan troglodytes). However, how humans and chimpanzees compare in solving spatial tasks during real-world foraging is unclear to date, as measuring such spatial abilities in natural habitats is challenging. Here we compared spatial movement patterns of the Mbendjele BaYaka people and the Taï chimpanzees during their daily search for food in rainforests. We measured linearity and speed during off-trail travels toward out-of-sight locations as proxies for spatial knowledge. We found similarly high levels of linearity in individuals of Mbendjele foragers and Taï chimpanzees. However, human foragers and chimpanzees clearly differed in their reactions to group size and familiarity with the foraging areas. Mbendjele foragers increased travel linearity with increasing familiarity and group size, without obvious changes in speed. This pattern was reversed in Taï chimpanzees. We suggest that these differences between Mbendjele foragers and Taï chimpanzees reflect their different ranging styles, such as life-time range size and trail use. This result highlights the impact of socio-ecological settings on comparing spatial movement patterns. Our study provides a first step toward comparing long-range spatial movement patterns of two closely-related species in their natural environments.
Application of a Limit-Cycle Oscillator Model for Prediction of Circadian Phase in Rotating Night Shift Workers
Authors: Stone Julia E. , Aubert Xavier L. , Maass Henning , Phillips Andrew J. K. , Magee Michelle , Howard Mark E. , Lockley Steven W. , Rajaratnam Shantha M. W. , Sletten Tracey L.
Published: July 2019

Practical alternatives to gold-standard measures of circadian timing in shift workers are needed. We assessed the feasibility of applying a limit-cycle oscillator model of the human circadian pacemaker to estimate circadian phase in 25 nursing and medical staff in a field setting during a transition from day/evening shifts (diurnal schedule) to 3–5 consecutive night shifts (night schedule). Ambulatory measurements of light and activity recorded with wrist actigraphs were used as inputs into the model. Model estimations were compared to urinary 6-sulphatoxymelatonin (aMT6s) acrophase measured on the diurnal schedule and last consecutive night shift. The model predicted aMT6s acrophase with an absolute mean error of 0.69 h on the diurnal schedule (SD = 0.94 h, 80% within ±1 hour), and 0.95 h on the night schedule (SD = 1.24 h, 68% within ±1 hour). The aMT6s phase shift from diurnal to night schedule was predicted to within ±1 hour in 56% of individuals. Our findings indicate the model can be generalized to a shift work setting, although prediction of inter-individual variability in circadian phase shift during night shifts was limited. This study provides the basis for further adaptation and validation of models for predicting circadian phase in rotating shift workers.
Correlation between Jejunal Microbial Diversity and Muscle Fatty Acids Deposition in Broilers Reared at Different Ambient Temperatures
Authors: Li Xing , Cao Zhenhui , Yang Yuting , Chen Liang , Liu Jianping , Lin Qiuye , Qiao Yingying , Zhao Zhiyong , An Qingcong , Zhang Chunyong , Li Qihua , Ji Qiaoping , Zhang Hongfu , Pan Hongbin
Published: July 2019

Temperature, which is an important environmental factor in broiler farming, can significantly influence the deposition of fatty acids in muscle. 300 one-day-old broiler chicks were randomly divided into three groups and reared at high, medium and low temperatures (HJ, MJ and LJ), respectively. Breast muscle and jejunal chyme samples were collected and subjected to analyses of fatty acid composition and 16S rRNA gene sequencing. Through spearman’s rank correlation coefficient, the data were used to characterize the correlation between jejunal microbial diversity and muscle fatty acid deposition in the broilers. The results showed that Achromobacter, Stenotrophomonas, Pandoraea, Brevundimonas, Petrobacter and Variovorax were significantly enriched in the MJ group, and all of them were positively correlated with the fatty acid profiling of muscle and multiple lipid metabolism signaling pathways. Lactobacillus was significantly enriched in the HJ group and exhibited a positive correlation with fatty acid deposition. Pyramidobacter, Dialister, Bacteroides and Selenomonas were significantly enriched in the LJ group and displayed negative correlation with fatty acid deposition. Taken together, this study demonstrated that the jejunal microflora manifested considerable changes at high and low ambient temperatures and that jejunal microbiota changes were correlated with fatty acid deposition of muscle in broilers.
Serum anti-EIF3A autoantibody as a potential diagnostic marker for hepatocellular carcinoma
Authors: Heo Chang-Kyu , Hwang Hai-Min , Lee Hye-Jung , Kwak Sang-Seob , Yoo Jong-Shin , Yu Dae-Yeul , Lim Kook-Jin , Lee Soojin , Cho Eun-Wie
Published: July 2019

Tumor-associated autoantibodies are promising diagnostic biomarkers for early detection of tumors. We have screened a novel tumor-associated autoantibody in hepatocellular carcinoma (HCC) model mice. Its target antigen was identified as eukaryotic translation initiation factor 3 subunit A (EIF3A) by proteomic analysis, and the elevated expression of EIF3A in HCC tissues of tumor model mice as well as human patients was shown. Also, its existence in tumor-derived exosomes was revealed, which seem to be the cause of tumor-associated autoantibody production. To use serum anti-EIF3A autoantibody as biomarker, ELISA detecting anti-EIF3A autoantibody in human serum was performed using autoantibody-specific epitope. For the sensitive detection of serum autoantibodies its specific conformational epitopes were screened from the random cyclic peptide library, and a streptavidin antigen displaying anti-EIF3A autoantibody-specific epitope, XC90p2(-CPVRSGFPC-), was used as capture antigen. It distinguished patients with HCC (n = 102) from healthy controls (n = 0285) with a sensitivity of 79.4% and specificity of 83.5% (AUC = 0.87). Also, by simultaneously detecting with other HCC biomarkers, including alpha-fetoprotein, HCC diagnostic sensitivity improved from 79.4% to 85%. Collectively, we suggest that serum anti-EIF3A autoantibody is a useful biomarker for the diagnosis of HCC and the combinational detection of related biomarkers can enhance the accuracy of the cancer diagnosis.
The N-fixing legume Periandra mediterranea constrains the invasion of an exotic grass (Melinis minutiflora P. Beauv) by altering soil N cycling
Authors: Nogueira Carina B. , Menéndez Esther , Ramírez-Bahena Martha Helena , Velázquez Encarna , Peix Álvaro , Mateos Pedro F. , Scotti Maria Rita
Published: July 2019

Melinis minutiflora is an invasive species that threatens the biodiversity of the endemic vegetation of the campo rupestre biome in Brazil, displacing the native vegetation and favouring fire spread. As M. minutiflora invasion has been associated with a high nitrogen (N) demand, we assessed changes in N cycle under four treatments: two treatments with contrasting invasion levels (above and below 50%) and two un-invaded control treatments with native vegetation, in the presence or absence of the leguminous species Periandra mediterranea. This latter species was considered to be the main N source in this site due to its ability to fix N2 in association with Bradyrhizobia species. Soil proteolytic activity was high in treatments with P. mediterranea and in those severely invaded, but not in the first steps of invasion. While ammonium was the N-chemical species dominant in plots with native species, including P.mediterranea, soil nitrate prevailed only in fully invaded plots due to the stimulation of the nitrifying bacterial (AOB) and archaeal (AOA) populations carrying the amoA gene. However, in the presence of P. mediterranea, either in the beginning of the invasion or in uninvaded plots, we observed an inhibition of the nitrifying microbial populations and nitrate formation, suggesting that this is a biotic resistance strategy elicited by P. mediterranea to compete with M. minutiflora. Therefore, the inhibition of proteolytic activity and the nitrification process were the strategies elicited by P.mediterranea to constrain M.munitiflora invasion.
Inverse Design Tool for Ion Optical Devices using the Adjoint Variable Method
Authors: Neustock Lars Thorben , Hansen Paul C. , Russell Zachary E. , Hesselink Lambertus
Published: July 2019

We present a computer-aided design tool for ion optical devices using the adjoint variable method. Numerical methods have been essential for the development of ion optical devices such as electron microscopes and mass spectrometers. Yet, the detailed computational analysis and optimization of ion optical devices is still onerous, since the governing equations of charged particle optics cannot be solved in closed form. Here, we show how to employ the adjoint variable method on the finite-element method and Störmer-Verlet method for electrostatic charged particle devices. This method allows for a full sensitivity analysis of ion optical devices, providing a quantitative measure of the effects of design parameters to device performance, at near constant computational cost with respect to the number of parameters. To demonstrate this, we perform such a sensitivity analysis for different freeform N-element Einzel lens systems including designs with over 13,000 parameters. We further show the optimization of the spot size of such lenses using a gradient-based method in combination with the adjoint variable method. The computational efficiency of the method facilitates the optimization of shapes and applied voltages of all surfaces of the device.
Amino acids as nutritional factors and (p)ppGpp as an alarmone of the stringent response regulate natural transformation in Micrococcus luteus
Authors: Lichev Antoni , Angelov Angel , Cucurull Inigo , Liebl Wolfgang
Published: July 2019

Natural competence for genetic transformation refers to the natural ability of various bacteria to take up exogenous DNA from their surroundings and to incorporate internalized genetic information into their genomes. By promoting bacterial diversification and adaptability, this process represents a major driving force in bacterial evolution. Micrococcus luteus was one of the first organisms used to study natural transformation in bacteria. Since then, however, only very little information about this phenomenon has been reported in M. luteus or in any member of the Actinobacteria phylum (low-GC Gram-positive bacteria). Previous work in our group indicated major differences between the transformation apparatus of M. luteus and the transformation machinery described for various Gram-negative and Gram-positive model bacteria belonging to the phyla Proteobacteria and Firmicutes (high-GC Gram-positive bacteria). This prompted us to initiate a study concerning the regulation mechanism of competence development in M. luteus. In this report, we identify amino acids as a nutritional factor that influences competence in a concentration-dependent manner. By using a transcriptional reporter strain for one of the late competence genes, we demonstrate how increasing concentrations of both amino acids mixtures and single amino acids supplemented to the growth medium affect transformability on transcriptional and post-transcriptional level. Furthermore, we revisit previously generated auxotrophic mutants to show that the transformation machinery is turned down during a state of extreme hunger for amino acids presumably as a part of a general response to auxotrophy. Finally, by generating and analysing knockout mutants for two predicted stringent response enzymes, we provide evidence for the involvement of the alarmone (p)ppGpp as a putative mediator of the effects on transformation development caused by amino acids. As a member of the Actinobacteria phylum, M. luteus could serve as a model for other representatives of the phylum, including a number of important human pathogens.
An Exact Approach to Elimination of Leakage in a Qubit Embedded in a Three-level System
Authors: Sun Yifan , Zhang Jun-Yi , Wu Lian-Ao
Published: July 2019

Leakage errors damage a qubit by coupling it to other levels. Over the years, several theoretical approaches to dealing with such errors have been developed based on perturbation arguments. Here we propose a different strategy: we use a sequence of finite rotation gates to exactly eliminate leakage errors. The strategy is illustrated by the recently proposed charge quadrupole qubit in a triple quantum dot, where there are two logical states to encode the qubit and one leakage state. We found an su(2) subalgebra in the three-level system, and by using the subalgebra we show that ideal Pauli x and z rotations, which are universal for single-qubit gates, can be generated by two or three propagators. In addition, the magnitude of detuning fluctuation can be estimated based on the exact solution.