bluuebunny/crossref_metadata_2025 huggingface dataset:
Sickle cell disease in Germany: Results from a national registry
Authors: Kunz Joachim B. , Lobitz Stephan , Grosse Regine , Oevermann Lena , Hakimeh Dani , Jarisch Andrea , Cario Holger , Beier Rita , Schenk Daniela , Schneider Dominik , Groß‐Wieltsch Ute , Prokop Aram , Heine Sabine , Khurana Claudia , Erlacher Miriam , Dürken Matthias , Linke Christina , Frühwald Michael , Corbacioglu Selim , Claviez Alexander , Metzler Markus , Ebinger Martin , Full Hermann , Wiesel Thomas , Eberl Wolfgang , Reinhard Harald , Tagliaferri Laura , Allard Pierre , Karapanagiotou‐Schenkel Irini , Rother Lisa‐Marie , Beck Dorothea , Le Cornet Lucian , Kulozik Andreas E. ,   German Sickle Cell Disease Registry
Published: December 2019

Background

Limited data on the prevalence and medical care of sickle cell disease (SCD) in Germany are available. Here, we make use of a patient registry to characterize the burden of disease and the treatment modalities for patients with SCD in Germany.

Procedure

A nationwide German registry for patients with SCD documents basic data on diagnosis and patient history retrospectively at the time of registration. A prospective annual documentation provides more details on complications and treatment of SCD. For the current analyses, data of 439 patients were available.

Results

Most patients had homozygous SCD (HbSS 75.1%, HbS/β‐thalassemia 13.2%, and HbSC 11.3%). The median age at diagnosis was 1.9 years (interquartile range, 0.6‐4.4 years), most patients were diagnosed when characteristic symptoms occurred. Sepsis and stroke had affected 3.2% and 4.2% of patients, respectively. During the first year of observation, 48.3% of patients were admitted to a hospital and 10.1% required intensive care. Prophylactic penicillin was prescribed to 95.6% of patients with homozygous SCD or HbS/β thalassemia below the age of six and hydroxycarbamide to 90.4% of patients above the age of two years. At least one annual transcranial Doppler ultrasound was documented for 74.8% of patients between 2 and 18 years.

Conclusion

With an estimated number of at least 2000, the prevalence of SCD in Germany remains low. Prospectively, we expect that the quality of care for children with SCD will be further improved by an earlier diagnosis after the anticipated introduction of a newborn screening program for SCD.
Polyphenol profile comparisons of seed coats of five pulse crops using a semi‐quantitative liquid chromatography‐mass spectrometric method
Authors: Elessawy Fatma M. , Bazghaleh Navid , Vandenberg Albert , Purves Randy W.
Published: December 2019

Pulse crops are nutritious, but their seed coats are typically discarded, despite their high content of polyphenols. Polyphenol diversity among seed coats of five pulse crops was examined using a 30‐min liquid chromatography‐mass spectrometry (LC‐MS) method. Notable differences within polyphenol classes were observed among crops and genotypes. Polyphenol profiling is the first step in understanding how pulse crop seed coats can be better utilised and also in ultimately determining which polyphenols and biochemical pathways are important for human health benefits.
Streamlined Development of Targeted Mass Spectrometry‐Based Method Combining Scout‐MRM and a Web‐Based Tool Indexed with Scout Peptides
Authors: Ayciriex Sophie , Carrière Romain , Bardet Chloé , Blanc J. C. Yves Le , Salvador Arnaud , Fortin Tanguy , Lemoine Jérôme
Published: December 2019

MS‐based targeted proteomics is a relevant technology for sensitive and robust relative or absolute quantification of proteins biomarker candidates in complex human biofluids or tissue extracts. Performing a multiplex assay imposes time scheduling of peptide monitoring only around their expected retention time that needs to be defined with synthetic peptide. Time‐scheduled monitoring is clearly a constraint that precludes from straightforward assay transfer between biological matrices or distinct experimental setup. Any unexpected retention time (RT) shift challenges assay robustness and its implementation for large‐scale analysis. Recently, Scout‐multiple reaction monitoring that fully releases multiplexed targeted acquisition from RT scheduling by successively monitoring complex transition groups triggered with sentinel molecules called Scout has been introduced. It is herein documented how Peptide Selector database and tool streamlines the building of a multiplexed method thanks to RT indexation relative to Scout peptides. This case study deals with surrogate peptides of biomarker candidates related to drug‐induced liver and vascular injury, running such on‐line built method (eight Scouts triggering the monitoring of a total of 692 transitions) enables 100% recovery of a panel of 93 spiked‐in heavy labeled standards, despite significant RT shifts between serum, plasma, or urine. This result illustrates the simplicity of automatically building and deploying robust proteomics targeted assay.
Equilibrium Morphologies of Faceted GaN under the Metalorganic Vapor‐Phase Epitaxy Condition: Wulff Construction Using Absolute Surface Energies
Authors: Seta Yuki , Pradipto Abdul-Muizz , Akiyama Toru , Nakamura Kohji , Ito Tomonori
Published: December 2019

An equilibrium Wulff construction using absolute surface energies for various orientations is conducted to elucidate the morphology change of GaN under the metalorganic vapor‐phase epitaxy (MOVPE) condition. The calculated equilibrium shapes suggest that the morphology mainly consists of and facets under Ga‐rich condition for selective area growth (SAG) on lateral direction. In contrast, an equilibrium crystal shape including the larger area of facets and (0001) plateau with smaller facets emerges under N‐rich condition. Furthermore, by incorporating growth conditions such as growth temperature and carrier gas, it is found that the (0001) plateau hardly emerges under H2 carrier gas condition at low temperature. The results under H2 carrier gas are found to be different from those under N2 carrier gas where the (0001) plateau slightly emerges at low temperature. The calculated results manifest that our approach can provide the determination of equilibrium shape of semiconductor materials during epitaxial growth.
An evaluation of operational and research weather forecasts for southern West Africa using observations from the DACCIWA field campaign in June–July 2016
Authors: Kniffka Anke , Knippertz Peter , Fink Andreas H. , Benedetti Angela , Brooks Malcolm E. , Hill Peter G. , Maranan Marlon , Pante Gregor , Vogel Bernhard
Published: December 2019

Reliable and accurate weather forecasts, particularly those of rainfall and its extremes, have the potential to improve living conditions in densely populated southern West Africa (SWA). The limited availability of observations has long impeded a rigorous evaluation of current state‐of‐the‐art forecast models. The field campaign of the Dynamics‐Aerosol‐Chemistry‐Cloud Interactions in West Africa (DACCIWA) project in June–July 2016 has created an unprecedentedly dense set of measurements from surface stations and radiosondes. Here we present results from a comprehensive evaluation of both numerical model forecasts and satellite products using these data on a regional and local level. Results reveal a substantial observational uncertainty showing considerable underestimations in satellite estimates of rainfall and low‐cloud cover with little correlation at the local scale. Models have a dry bias of 0.1–1.9  in rainfall and too low column relative humidity. They tend to underestimate low clouds, leading to excess surface solar radiation of 43 . Remarkably, most models show some skill in representing regional modulations of rainfall related to synoptic‐scale disturbances, while local variations in rainfall and cloudiness are hardly captured. Slightly better results are found with respect to temperature and for the post‐onset rather than for the pre‐onset period. Delicate local features such as the Maritime Inflow phenomenon are also rather poorly represented, leading to too cool, dry and cloudy conditions at the coast. Differences between forecast days 1 and 2 are relatively small and hardly systematic, suggesting a relatively quick error saturation. Using explicit convection leads to more realistic spatial variability in rainfall, but otherwise no marked improvement. Future work should aim at improving the subtle balance between the diurnal cycles of low clouds, surface radiation, the boundary layer and convection. Further efforts are also needed to improve the observational system beyond field campaign periods.
GPS‐level accurate camera localization with HorizonNet
Authors: Grelsson Bertil , Robinson Andreas , Felsberg Michael , Khan Fahad Shahbaz
Published: December 2019

This paper investigates the problem of position estimation of unmanned surface vessels (USVs) operating in coastal areas or in the archipelago. We propose a position estimation method where the horizon line is extracted in a 360° panoramic image around the USV. We design a convolutional neural network (CNN) architecture to determine an approximate horizon line in the image and implicitly determine the camera orientation (the pitch and roll angles). The panoramic image is warped to compensate for the camera orientation and to generate an image from an approximately level camera. A second CNN architecture is designed to extract the pixelwise horizon line in the warped image. The extracted horizon line is correlated with digital elevation model data in the Fourier domain using a minimum output sum of squared error correlation filter. Finally, we determine the location of the maximum correlation score over the search area to estimate the position of the USV. Comprehensive experiments are performed in field trials conducted over 3 days in the archipelago. Our approach provides excellent results by achieving robust position estimates with global positioning system (GPS)‐level accuracy in previously unvisited test areas.
Cell‐Free Protein Synthesis in Bifunctional Hyaluronan Microgels: A Strategy for In Situ Immobilization and Purification of His‐Tagged Proteins
Authors: Heida Thomas , Köhler Tony , Kaufmann Anika , Männel Max J. , Thiele Julian
Published: December 2019

In current cell‐free biotechnology, mimicking physicochemical aspects of cellular life while providing efficient protein synthesis, separation, and purification is a crucial step towards truly applicable artificial, yet cell‐like, biosynthesis platforms. To achieve simultaneous synthesis and immobilization of proteins in a tailor‐made environment, we link DNA encoding for histidine‐tagged proteins to microfluidically prepared microgels via strain‐promoted azide‐alkyne cycloaddition and introduce nitrilotriacetic acid moieties that exhibit affinity towards histidine‐tagged proteins upon nickel activation. After swelling the microgels in a prokaryotic protein synthesis machinery, proteins are produced and remain at the site of synthesis despite the membrane‐free, open nature of the gels. The protein‐loaded microgels are then separated from the complex bioreaction mixture and proteins are released by a chemical trigger. Our bifunctional microgels not only contribute to the ongoing design of artificial cells but also allow for directly linking proteins to specific DNA, which can be explored for genotype‐phenotype correlation in DNA mutagenesis.
An intercomparison of subtropical cut-off lows in the Southern Hemisphere using recent reanalyses: ERA-Interim, NCEP-CFRS, MERRA-2, JRA-55, and JRA-25
Authors: Pinheiro Henri Rossi , Hodges Kevin Ivan , Gan Manoel Alonso
Published: December 2019

Four recent reanalysis products ERA-Interim, NCEP-CFSR, MERRA-2 and JRA-55 are evaluated and compared to an older reanalysis JRA-25, to quantify their confidence in representing Cut-off lows (COLs) in the Southern Hemisphere. The climatology of COLs based on the minima of 300-hPa vorticity ($$\xi_{300}$$ξ300) and 300-hPa geopotential ($$Z_{300}$$Z300) provides different perspectives of COLs and contributes to the understanding of the discrepancies observed in the literature regarding their numbers and seasonality. The COLs compare better among the newest reanalyses than compared to the older reanalysis JRA-25. The difference in number between the latest reanalyses are generally small for both $$\xi_{300}$$ξ300 and, with more COLs identified in $$\xi_{300}$$ξ300 than in $$Z_{300}$$Z300 for all reanalyses. The spatial differences observed between the newest reanalyses are mainly due to differences in the track lengths, which is larger in ERA-Interim and JRA-55 than in NCEP-CFSR and MERRA-2, resulting in disparities in the track density. This is likely due to the difference in the assimilation data system used in each reanalysis product. The largest differences in intensities occur in the $$\xi_{300}$$ξ300, because this field is very sensitive to the reanalysis resolution. The mean separation distance of the COLs that match between the latest reanalyses are generally small, while the older JRA-25 has a broader distribution and larger number of matches with relatively large distances, indicating larger uncertainties in location of COLs. The results show significant improvements for the most recent reanalyses compared to the older JRA-25 reanalysis, indicating a progress in representing the COL properties.
Splenic NKG2D confers resilience versus susceptibility in mice after chronic social defeat stress: beneficial effects of (R)-ketamine
Authors: Zhang Kai , Sakamoto Akemi , Chang Lijia , Qu Youge , Wang Siming , Pu Yaoyu , Tan Yunfei , Wang Xingming , Fujita Yuko , Ishima Tamaki , Hatano Masahiko , Hashimoto Kenji
Published: December 2019

The spleen is a large immune organ that plays a key role in the immune system. The precise molecular mechanisms underlying the relationship between the spleen and stress-related psychiatric disorders are unknown. Here we investigated the role of spleen in stress-related psychiatric disorders. FACS analysis was applied to determine the contribution of the spleen to susceptibility and resilience in mice that were subjected to chronic social defeat stress (CSDS). We found a notable increase in splenic volume and weight in CSDS-susceptible mice compared to control (no CSDS) mice and CSDS-resilient mice. The number of granulocytes, but not of T cells and B cells, in the spleen of susceptible mice was higher than in the spleen of both control and resilient mice. Interestingly, NKG2D (natural killer group 2, member D) expression in the spleen of CSDS-susceptible mice was higher than that in control mice and CSDS-resilient mice. In addition, NKG2D expression in the spleen of patients with depression was higher than that in controls. Both increased splenic weight and increased splenic NKG2D expression in CSDS-susceptible mice were ameliorated after a subsequent administration of (R)-ketamine. The present findings indicate a novel role of splenic NKG2D in stress susceptibility versus resilience in mice subjected to CSDS. Furthermore, abnormalities in splenic functions in CSDS-susceptible mice were ameliorated after subsequent injection of (R)-ketamine. Thus, the brain–spleen axis might, at least in part, contribute to the pathogenesis of stress-related psychiatric disorders such as depression.
Swimming upstream: community economies for a different coastal rural development in Sweden
Authors: Arias Schreiber Milena , Wingren Ida , Linke Sebastian
Published: December 2019

The EU Blue Growth agenda is being implemented at a time when European coastal fisheries and traditional fishing communities are struggling to survive or have already vanished from areas where they used to flourish. Driven by the strong conviction that current disadvantaged and vulnerable coastal fishers still have a central role to play in rural development, local level initiatives are calling for a different future for this fishery sector. The participants in these initiatives insist that coastal fisheries should not be driven to extinction, despite their low economic profitability and thus minimal contribution to economic growth compared to large-scale enterprises. Through participatory observation and informal interviews, we investigate one of these local level initiatives on the Swedish Baltic Sea coast and analyse how it aligns with a community economies’ project based on a different economic perspective. We describe first the primary activities carried out by the initiative and follow by an examination on what drove it, how it has been maintained, and how it might spread. We conclude on the potentials of the community economies framework and project to advance a Blue degrowth agenda based on difference and not necessarily less.
Rescuing Informed Consent: How the new “Key Information” and “Reasonable Person” Provisions in the Revised U.S. Common Rule open the door to long Overdue Informed Consent Disclosure Improvements and why we need to walk Through that door
Authors: Yarborough Mark
Published: December 2019

There is substantial published evidence showing that countless people enroll each year in ethically deficient clinical trials. Many of the trials are problematic because the quality of the science used to justify their launch may not be sufficiently vetted while many other trials may lack requisite social value. This poses the question: why do people volunteer for them? The answer resides in large part in the fact that informed consent practices have historically masked, rather than disclosed, the information that would alert research candidates to the ethically problematic nature of the trials. The “reasonable person” and “key information” provisions in the revised US Common Rule create the opportunity to correct this historical shortcoming. Two sources are employed to shed light on what the “key information” is that should be disclosed to a “reasonable person”: the original disclosure aims of the Nuremberg Code, as well as an extensive body of meta-research evidence. Those sources jointly support a range of new disclosures in the informed consent process that would unmask the heretofore undisclosed information. The resulting proposed new disclosures pertain to the overall success prospects of clinical trials, the quality of the prior research that both forms the basis of clinical trials and informs assessment of their risks and benefits, the potential social value of clinical trials, and the commercial purposes of clinical trials.
A practical guide to placental examination for forensic pathologists
Authors: Mittal Namita , Byard Roger W. , Dahlstrom Jane E.
Published: December 2019

The placenta is a complex interface organ that may hold clues to the reasons for fetal, neonatal or maternal demise. For this reason, placental examination should be a mandatory part of all perinatal or maternal autopsies. While published protocols for the examination of the placenta exist, they are often not adopted. The following review provides practical guidelines for placental examination, with discussion of specific medical conditions that can negatively impact upon the fetus, neonate or mother involving placental pathology to cause death. The review aims to discuss concepts, with illustrations, that forensic pathologists may not routinely focus on in death investigations that may either contribute or mask the cause of a fetal or neonatal death, or are associated with a recurrence risk. While it is recognized that many forensic facilities do not have formal guidelines for placental examination, involvement of local perinatal pathology services in cases is one way of obtaining additional specialist expertise.
Strengthen user authentication on mobile devices by using user’s touch dynamics pattern
Authors: Teh Pin Shen , Zhang Ning , Tan Syh-Yuan , Shi Qi , Khoh Wee How , Nawaz Raheel
Published: December 2019

Mobile devices, particularly the touch screen mobile devices, are increasingly used to store and access private and sensitive data or services, and this has led to an increased demand for more secure and usable security services, one of which is user authentication. Currently, mobile device authentication services mainly use a knowledge-based method, e.g. a PIN-based authentication method, and, in some cases, a fingerprint-based authentication method is also supported. The knowledge-based method is vulnerable to impersonation attacks, while the fingerprint-based method can be unreliable sometimes. To overcome these limitations and to make the authentication service more secure and reliable for touch screen mobile device users, we have investigated the use of touch dynamics biometrics as a mobile device authentication solution by designing, implementing and evaluating a touch dynamics authentication method. This paper describes the design, implementation, and evaluation of this method, the acquisition of raw touch dynamics data, the use of the raw data to obtain touch dynamics features, and the training of the features to build an authentication model for user identity verification. The evaluation results show that by integrating the touch dynamics authentication method into the PIN-based authentication method, the protection levels against impersonation attacks is greatly enhanced. For example, if a PIN is compromised, the success rate of an impersonation attempt is drastically reduced from 100% (if only a 4-digit PIN is used) to 9.9% (if both the PIN and the touch dynamics are used).
The block-constrained configuration model
Authors: Casiraghi Giona
Published: December 2019

We provide a novel family of generative block-models for random graphs that naturally incorporates degree distributions: the block-constrained configuration model. Block-constrained configuration models build on the generalized hypergeometric ensemble of random graphs and extend the well-known configuration model by enforcing block-constraints on the edge-generating process. The resulting models are practical to fit even to large networks. These models provide a new, flexible tool for the study of community structure and for network science in general, where modeling networks with heterogeneous degree distributions is of central importance.
MULTIVARIATE LONG-MEMORY COHORT MORTALITY MODELS
Authors: Yan Hongxuan , Peters Gareth W. , Chan Jennifer S.K.
Published: December 2019

The existence of long memory in mortality data improves the understandings of features of mortality data and provides a new approach for establishing mortality models. The findings of long-memory phenomena in mortality data motivate us to develop new mortality models by extending the Lee–Carter (LC) model to death counts and incorporating long-memory model structure. Furthermore, there are no identification issues arising in the proposed model class. Hence, the constraints which cause many computational issues in LC models are removed. The models are applied to analyse mortality death count data sets from three different countries divided according to genders. Bayesian inference with various selection criteria is applied to perform the model parameter estimation and mortality rate forecasting. Results show that multivariate long-memory mortality model with long-memory cohort effect model outperforms multivariate extended LC cohort model in both in-sample fitting and out-sample forecast. Increasing the accuracy of forecasting of mortality rates and improving the projection of life expectancy is an important consideration for insurance companies and governments since misleading predictions may result in insufficient funds for retirement and pension plans.
Case of mistaken identity: resolving the taxonomy between Trioza eugeniae Froggatt and T. adventicia Tuthill (Psylloidea: Triozidae)
Authors: Taylor Gary S. , Martoni Francesco
Published: December 2019

The ‘Eugenia psyllid’ or ‘Lilly pilly psyllid’, widely recognized in Australia and in the USA as Trioza eugeniae Froggatt (Hemiptera: Triozidae), is not T. eugeniae, but rather T. adventicia Tuthill. In this study we assessed morphological comparisons of materials from throughout the native and introduced ranges and re-examined original descriptions of both taxa, together with Froggatt's type specimens of T. eugeniae. Furthermore, through DNA barcoding analyses, we confirmed the validity of both T. adventicia and T. eugeniae as separate species. We re-described both species to include additional characters not previously included and designated a lectotype for T. eugeniae. T. eugeniae has smaller fore wings that are slightly more elongate. These lack infuscation around veins R and R1, vein Rs is relatively longer, meeting the costa closer to the wing apex; with certain veins bearing long, fine divergent setae, a character not previously described. It has consistently three inner and one outer metatibial spurs. The male parameres appear narrowly pyriform with a weak dorsolateral lobe and weakly sclerotized apices. T. adventicia has larger fore wings that are slightly more ovate with dark infuscation around veins R and R1; vein Rs is relatively shorter, meeting the costa further from the wing apex, with veins lacking long, fine divergent setae. The usual configuration of two inner and one outer metatibial spurs, previously used to separate the two species, appears inconsistent. The male parameres appear a little more broadly pyriform with slightly more sclerotized apices. T. eugeniae refers to a distinct species which has a restricted distribution only in its native range in southern subcoastal New South Wales, Australia. T. adventicia refers to a separate species, with a natural distribution in eastern subcoastal Australia, but has been introduced widely in southern Australia, to New Zealand and the USA. This study elucidates a long history of misidentification of T. eugeniae in the nursery industry and in almost 30 years of literature on its biological control in the USA. Regardless, the biological control program, unknowingly, targeted the correct species of psyllid, T. adventicia, in its foreign exploration and importation of the appropriate parasitoid as a biocontrol agent in the USA. Despite being firmly entrenched in both the nursery trade and scientific literature, the name T. eugeniae is misapplied. While the acceptance of the valid name, T. adventicia, might be regarded as both problematic and protracted, this is the correct taxonomical attribution.
Mangrove species maintains constant nutrient resorption efficiency under eutrophic conditions
Authors: Wei Lili , Kao Shuh-Ji , Liu Chaoxiang
Published: December 2019

Mangrove species have developed nutrient conservation mechanisms to adapt to oligotrophic intertidal environments. However, nutrient enrichment occurs worldwide, particularly in estuarine and coastal regions. Mangrove species may change their adaptive strategies if nutrient availability increases substantially. To understand how nutrient resorption (a major nutrient conservation strategy) responds to nutrient enrichment, a common mangrove species in China, Aegiceras corniculatum (black mangrove), was selected, and saplings were cultivated in nutrient-enriched soils. After one year, neither N nor P resorption efficiency showed significant variations with nutrient availability and there was no difference between N and P resorption efficiency. Overall, nutrient resorption efficiency of A. corniculatum remained at ∼40%, lower than the global average levels of evergreen plants (∼50%), indicating incomplete resorption of nutrients. Incomplete resorption was also evidenced by the nutrient concentrations, resorption proficiency and N: P ratio of plant leaves. Collectively, these results indicate that black mangrove can maintain constant nutrient resorption efficiency under eutrophic conditions.
How to prove decidability of equational theories with second-order computation analyser SOL
Authors: HAMANA MAKOTO
Published: December 2019

We present a general methodology of proving the decidability of equational theory of programming language concepts in the framework of second-order algebraic theories. We propose a Haskell-based analysis tool, i.e. Second-Order Laboratory, which assists the proofs of confluence and strong normalisation of computation rules derived from second-order algebraic theories. To cover various examples in programming language theory, we combine and extend both syntactical and semantical results of the second-order computation in a non-trivial manner. We demonstrate how to prove decidability of various algebraic theories in the literature. It includes the equational theories of monad and λ-calculi, Plotkin and Power’s theory of states and bits, and Stark’s theory of π-calculus. We also demonstrate how this methodology can solve the coherence of monoidal categories.
THE UNIT MAP OF THE ALGEBRAIC SPECIAL LINEAR COBORDISM SPECTRUM
Authors: Yakerson Maria
Published: December 2019

In the joint work with Elmanto, Hoyois, Khan and Sosnilo, we computed infinite$\mathbb{P}^{1}$-loop spaces of motivic Thom spectra using the technique of framed correspondences. This result allows us to express non-negative$\mathbb{G}_{m}$-homotopy groups of motivic Thom spectra in terms of geometric generators and relations. Using this explicit description, we show that the unit map of the algebraic special linear cobordism spectrum induces an isomorphism on$\mathbb{G}_{m}$-homotopy sheaves.
Arizona Twin Project: Specificity in Risk and Resilience for Developmental Psychopathology and Health
Authors: Lemery-Chalfant Kathryn , Oro Veronica , Rea-Sandin Gianna , Miadich Samantha , Lecarie Emma , Clifford Sierra , Doane Leah D. , Davis Mary C.
Published: December 2019

The Arizona Twin Project is an ongoing longitudinal study designed to elucidate gene–environment interplay underlying the development of risk and resilience to common mental and physical health problems during infancy, childhood and adolescence. Specificity of risk is carefully examined across mental and physical health and how these influences vary across socioeconomic and sociocultural environments. Participants are a sample of approximately 700 twins (31% Latinx) recruited from birth records in the state of Arizona, USA. Twins are 32% monozygotic twins, 36% same-sex dizygotic (DZ), 32% opposite-sex DZ, currently 10–11 years of age. Primary caregivers were interviewed on twins’ development and early physical and social environments when twins were 1, 2 and 5 years of age. In-depth objective measurement commenced in middle childhood, with in-person assessments at 8–11 years of age, with plans to continue to follow the sample across adolescence. Middle childhood measures focus on children’s physical and mental health, including diurnal cortisol, actigraphy-based measures of sleep and activity, cold pressor task assessing acute pain, and reaction time tasks assessing executive functioning. Preliminary findings illustrate that objective assessments of children’s health are highly heritable, but they do not always share genetic etiology with more commonly used subjective assessments. Exposure to early adversity moderates genetic influences on both executive functioning and health, with higher heritability typically seen under adverse conditions. Future directions include an examination of how pubertal stage affects genetic and environmental influences on diurnal cortisol, sleep, chronic pain, and mental health.
Finding Faults in Our Past: Uncovering the Messina Earthquake
Authors: Derouin Sarah
Published: December 2019

The source of the deadly 1908 Italian earthquake may finally be identified, thanks to a fresh look at the geomorphology of the Strait of Messina.
An Adaptive Forecasting Method for Ionospheric Critical Frequency of F2 Layer
Authors: Wang Jian , Feng Feng , Ma Jianguo
Published: December 2019

To achieve further improvements in quantitative predictability, a chaos‐based adaptive forecasting method for the critical frequency of the F2 layer (foF2) is proposed for the development of an ionospheric forecasting technique for one hour ahead. This method has three new characteristics. (1) It is based on Volterra filters and it has a simplified structure with easy implementation. (2) Based only on past measured data, it can forecast foF2 values without the requirement for past or forecast values of any solar and geomagnetic indices. (3) It can achieve high forecast accuracy with a small training dataset of 27 days (one solar rotation period). Diurnal, seasonal, and annual comparisons of measured and forecasted foF2 values are presented to illustrate the applicability and suitability of the proposed method. Statistical results reveal that the foF2 values calculated using the proposed model are consistent with the trend of measurements irrespective of whether geomagnetic conditions are quiet or disturbed. The average RMSE and RRMSE values were 0.86 MHz and 17.36%, respectively, when using measured data from periods of past 27 days during 2008–2015. The proposed method has potential to forecast other ionospheric characteristic parameters, and that it could achieve satisfactory regional or global 1‐hr forecasting if combined with a spatial reconstruction technique.
The β-catenin/YAP signaling axis is a key regulator of melanoma-associated fibroblasts
Authors: Liu Tianyi , Zhou Linli , Yang Kun , Iwasawa Kentaro , Kadekaro Ana Luisa , Takebe Takanori , Andl Thomas , Zhang Yuhang
Published: December 2019

β-catenin is a multifunctional protein that plays crucial roles in embryonic development, physiological homeostasis, and a wide variety of human cancers. Previously, we showed that in vivo targeted ablation of β-catenin in melanoma-associated fibroblasts after melanoma formation significantly suppressed tumor growth. However, when the expression of β-catenin was ablated in melanoma-associated fibroblasts before tumor initiation, melanoma development was surprisingly accelerated. How stromal β-catenin deficiency leads to opposite biological effects in melanoma progression is not completely understood. Here, we report that β-catenin is indispensable for the activation of primary human stromal fibroblasts and the mediation of fibroblast-melanoma cell interactions. Using coimmunoprecipitation and proximity ligation assays, we identified Yes-associated protein (YAP) as an important β-catenin-interacting partner in stromal fibroblasts. YAP is highly expressed in the nuclei of cancer-associated fibroblasts (CAFs) in both human and murine melanomas. Mechanistic investigation revealed that YAP nuclear translocation is significantly modulated by Wnt/β-catenin activity in fibroblasts. Blocking Wnt/β-catenin signaling in stromal fibroblasts inhibited YAP nuclear translocation. In the absence of YAP, the ability of stromal fibroblasts to remodel the extracellular matrix (ECM) was inhibited, which is consistent with the phenotype observed in cells with β-catenin deficiency. Further studies showed that the expression of ECM proteins and enzymes required for remodeling the ECM was suppressed in stromal fibroblasts after YAP ablation. Collectively, our data provide a new paradigm in which the β-catenin-YAP signaling axis regulates the activation and tumor-promoting function of stromal fibroblasts.
Skyrmion phase and competing magnetic orders on a breathing kagomé lattice
Authors: Hirschberger Max , Nakajima Taro , Gao Shang , Peng Licong , Kikkawa Akiko , Kurumaji Takashi , Kriener Markus , Yamasaki Yuichi , Sagayama Hajime , Nakao Hironori , Ohishi Kazuki , Kakurai Kazuhisa , Taguchi Yasujiro , Yu Xiuzhen , Arima Taka-hisa , Tokura Yoshinori
Published: December 2019

Magnetic skyrmion textures are realized mainly in non-centrosymmetric, e.g. chiral or polar, magnets. Extending the field to centrosymmetric bulk materials is a rewarding challenge, where the released helicity/vorticity degree of freedom and higher skyrmion density result in intriguing new properties and enhanced functionality. We report here on the experimental observation of a skyrmion lattice (SkL) phase with large topological Hall effect and an incommensurate helical pitch as small as 2.8 nm in metallic Gd3Ru4Al12, which materializes a breathing kagomé lattice of Gadolinium moments. The magnetic structure of several ordered phases, including the SkL, is determined by resonant x-ray diffraction as well as small angle neutron scattering. The SkL and helical phases are also observed directly using Lorentz-transmission electron microscopy. Among several competing phases, the SkL is promoted over a low-temperature transverse conical state by thermal fluctuations in an intermediate range of magnetic fields.
Author Correction: Large Enriched Fragment Targeted Sequencing (LEFT-SEQ) Applied to Capture of Wolbachia Genomes
Authors: Lefoulon Emilie , Vaisman Natalie , Frydman Horacio M. , Sun Luo , Voland Lise , Foster Jeremy M. , Slatko Barton E.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Angiotensin-Receptor-Associated Protein Modulates Ca2+ Signals in Photoreceptor and Mossy Fiber cells
Authors: Barro-Soria Rene , Caicedo Alejandro , Jägle Herbert , Merkel Laura , Zhao Na , Knop Gabriel , Gierke Kaspar , Dannullis Andrea , Castrop Hayo , Brandstätter Johann Helmut , Kirchhoff Frank , Feigenspan Andreas , Strauß Olaf
Published: December 2019

Fast, precise and sustained neurotransmission requires graded Ca2+ signals at the presynaptic terminal. Neurotransmitter release depends on a complex interplay of Ca2+ fluxes and Ca2+ buffering in the presynaptic terminal that is not fully understood. Here, we show that the angiotensin-receptor-associated protein (ATRAP) localizes to synaptic terminals throughout the central nervous system. In the retinal photoreceptor synapse and the cerebellar mossy fiber-granule cell synapse, we find that ATRAP is involved in the generation of depolarization-evoked synaptic Ca2+ transients. Compared to wild type, Ca2+ imaging in acutely isolated preparations of the retina and the cerebellum from ATRAP knockout mice reveals a significant reduction of the sarcoendoplasmic reticulum (SR) Ca2+-ATPase (SERCA) activity. Thus, in addition to its conventional role in angiotensin signaling, ATRAP also modulates presynaptic Ca2+ signaling within the central nervous system.
Robust latent-variable interpretation of in vivo regression models by nested resampling
Authors: Caulk Alexander W. , Janes Kevin A.
Published: December 2019

Simple multilinear methods, such as partial least squares regression (PLSR), are effective at interrelating dynamic, multivariate datasets of cell–molecular biology through high-dimensional arrays. However, data collected in vivo are more difficult, because animal-to-animal variability is often high, and each time-point measured is usually a terminal endpoint for that animal. Observations are further complicated by the nesting of cells within tissues or tissue sections, which themselves are nested within animals. Here, we introduce principled resampling strategies that preserve the tissue-animal hierarchy of individual replicates and compute the uncertainty of multidimensional decompositions applied to global averages. Using molecular–phenotypic data from the mouse aorta and colon, we find that interpretation of decomposed latent variables (LVs) changes when PLSR models are resampled. Lagging LVs, which statistically improve global-average models, are unstable in resampled iterations that preserve nesting relationships, arguing that these LVs should not be mined for biological insight. Interestingly, resampling is less discriminatory for multidimensional regressions of in vitro data, where replicate-to-replicate variance is sufficiently low. Our work illustrates the challenges and opportunities in translating systems-biology approaches from cultured cells to living organisms. Nested resampling adds a straightforward quality-control step for interpreting the robustness of in vivo regression models.
Author Correction: Hotspots of recent hybridization between pigs and wild boars in Europe
Authors: Iacolina Laura , Pertoldi Cino , Amills Marcel , Kusza Szilvia , Megens Hendrik-Jan , Bâlteanu Valentin Adrian , Bakan Jana , Cubric-Curik Vlatka , Oja Ragne , Saarma Urmas , Scandura Massimo , Šprem Nikica , Stronen Astrid Vik
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Episomal vectors based on S/MAR and the β-globin Replicator, encoding a synthetic transcriptional activator, mediate efficient γ-globin activation in haematopoietic cells
Authors: Stavrou Eleana F. , Simantirakis Emannuouil , Verras Meletios , Barbas Carlos , Vassilopoulos George , Peterson Kenneth R. , Athanassiadou Aglaia
Published: December 2019

We report the development of episomal vectors for the specific γ-globin transcription activation in its native position by activator Zif-VP64, based on the Scaffold/Matrix Attachment Region (S/MAR) for episomal retention and the β-globin Replicator, the DNA replication-Initiation Region from the β-globin locus. Vector Zif-VP64-Ep1 containing transcription cassettes CMV- Zif-VP64 and CMV-eGFP-S/MAR transfected a)K562 cells; b)murine β-YAC bone marrow cells (BMC); c)human haematopoietic progenitor CD34+ cells, with transfection efficiencies of 46.3 ± 5.2%, 23.0 ± 2.1% and 24.2 ± 2.4% respectively. K562 transfections generated stable cell lines running for 28 weeks with and without selection, with increased levels of γ-globin mRNA by 3.3 ± 0.13, of γ-globin protein by 6.75 ± 3.25 and HbF protein by 2 ± 0.2 fold, while the vector remained episomal and non integrated. In murine β-YAC BMCs the vector mediated the activation of the silent human γ-globin gene and in CD34+ cells, increased γ-globin mRNA, albeit only transiently. A second vector Zif-VP64-Ep2, with both transcription cassettes carrying promoter SFFV instead of CMV and the addition of β-globin Replicator, transferred into CD34+ cells, produced CD34+ eGFP+ cells, that generated colonies in colony forming cell cultures. Importantly, these were 100% fluorescent, with 2.11 ± 0.13 fold increased γ-globin mRNA, compared to non-transfected cells. We consider these episomal vectors valid, safer alternatives to viral vectors.
Growth performance and emergence of invasive alien Rumex confertus in different soil types
Authors: Kołodziejek Jeremi
Published: December 2019

Rumex confertus is known to be one of the most serious invasive weed species infesting meadows, pastures and ruderal lands throughout the Central Europe. Rumex confertus was grown in pot experiments using 8 soil types at 5 concentrations of nitrogen (N) and phosphorus (P). Based on harvest data, the variables, seedlings emergence, root: shoot (R: S) ratio, N and P concentration, chlorophyll content, Relative Colimitation Index (RCI) and dry matter allocation to plant components, were determined. N and P addition stimulated the growth of plants in different soils, as reflected by a significant increase in seedling growth parameters such as total plant biomass and shoot biomass. Across all soil types, emergence of seedlings was negatively affected by very high N, but positively affected by increased P availability. This study indicates that Dystric Arenosol, Entic Podzol, Brunic Arenosol and Calcaric Leptosol are unfavorable for R. confertus growth, excluding  R. confertus completely. Moreover, evidence suggests that plant growth is limited by both N and P, therefore R. confertus could be controlled by reducing available N and P content in the soil.
Detrended Multiple Cross-Correlation Coefficient applied to solar radiation, air temperature and relative humidity
Authors: Brito Andrea de Almeida , Araújo Heráclio Alves de , Zebende Gilney Figueira
Published: December 2019

Due to the importance of generating energy sustainably, with the Sun being a large solar power plant for the Earth, we study the cross-correlations between the main meteorological variables (global solar radiation, air temperature, and relative air humidity) from a global cross-correlation perspective to efficiently capture solar energy. This is done initially between pairs of these variables, with the Detrended Cross-Correlation Coefficient, ρDCCA, and subsequently with the recently developed Multiple Detrended Cross-Correlation Coefficient, $${\boldsymbol{DM}}{{\boldsymbol{C}}}_{{\bf{x}}}^{{\bf{2}}}$$DMCx2. We use the hourly data from three meteorological stations of the Brazilian Institute of Meteorology located in the state of Bahia (Brazil). Initially, with the original data, we set up a color map for each variable to show the time dynamics. After, ρDCCA was calculated, thus obtaining a positive value between the global solar radiation and air temperature, and a negative value between the global solar radiation and air relative humidity, for all time scales. Finally, for the first time, was applied $${\boldsymbol{DM}}{{\boldsymbol{C}}}_{{\bf{x}}}^{{\bf{2}}}$$DMCx2 to analyze cross-correlations between three meteorological variables at the same time. On taking the global radiation as the dependent variable, and assuming that $${\boldsymbol{DM}}{{\boldsymbol{C}}}_{{\bf{x}}}^{{\bf{2}}}={\bf{1}}$$DMCx2=1 (which varies from 0 to 1) is the ideal value for the capture of solar energy, our analysis finds some patterns (differences) involving these meteorological stations with a high intensity of annual solar radiation.
Immunity-related genes and signaling pathways under hypoxic stresses in Haliotis diversicolor: a transcriptome analysis
Authors: Sun Yulong , Zhang Xin , Wang Yilei , Day Robert , Yang Huiping , Zhang Ziping
Published: December 2019

Due to increased temperatures and aquaculture density, thermal and hypoxia stresses have become serious problems for the aquaculture of abalone Haliotis diversicolor. Stresses lead to immunosuppression, which can cause severe negative impacts on aquaculture farms. To study the mechanism of immunosuppression after hypoxia stress and bacterial challenge, transcriptomes of H. diversicolor hemocytes involved in immunity were profiled. A total of 307,395,572 clean reads were generated and assembled into 99,774 unigenes. KEGG analysis indicated that 225 unigenes with immunologic function were mapped into immune-related pathways. Expression of 41 unigenes measured by quantitative real-time PCR (qRT-PCR) showed consistent results with that of transcriptome analysis. When exposure challenge of Vibrio parahaemolyticus, it is indicated that the PI3K-AKT, MAPK, NF-κB and P53 signal pathways were involved in the hypoxia-induced immunosuppression of H. diversicolor. Furthermore, when the AKT gene (HdAKT) was inhibited by double-stranded RNA (dsRNA), expression levels of HdAKT was lower than the blank and control group in hemocytes at 4 h, 12 h and 24 h (p < 0.05).
Electro-mechanical Lung Simulator Using Polymer and Organic Human Lung Equivalents for Realistic Breathing Simulation
Authors: Pasteka Richard , Forjan Mathias , Sauermann Stefan , Drauschke Andreas
Published: December 2019

Simulation models in respiratory research are increasingly used for medical product development and testing, especially because in-vivo models are coupled with a high degree of complexity and ethical concerns. This work introduces a respiratory simulation system, which is bridging the gap between the complex, real anatomical environment and the safe, cost-effective simulation methods. The presented electro-mechanical lung simulator, xPULM, combines in-silico, ex-vivo and mechanical respiratory approaches by realistically replicating an actively breathing human lung. The reproducibility of sinusoidal breathing simulations with xPULM was verified for selected breathing frequencies (10–18 bpm) and tidal volumes (400–600 ml) physiologically occurring during human breathing at rest. Human lung anatomy was modelled using latex bags and primed porcine lungs. High reproducibility of flow and pressure characteristics was shown by evaluating breathing cycles (nTotal = 3273) with highest standard deviation |3σ| for both, simplified lung equivalents ($${{\boldsymbol{\mu }}}_{\dot{{\bf{V}}}}$$µV̇ = 23.98 ± 1.04 l/min, μP = −0.78 ± 0.63 hPa) and primed porcine lungs ($${{\boldsymbol{\mu }}}_{\dot{{\bf{V}}}}$$µV̇ = 18.87 ± 2.49 l/min, μP = −21.13 ± 1.47 hPa). The adaptability of the breathing simulation parameters, coupled with the use of porcine lungs salvaged from a slaughterhouse process, represents an advancement towards anatomically and physiologically realistic modelling of human respiration.