bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphorus absorption and gene expression levels of related transporters in the small intestine of broilers
Authors: Hu Yixin , Liao Xiudong , Wen Qian , Lu Lin , Zhang Liyang , Luo Xugang
Published: May 2018

To investigate the P absorption and gene expression levels of related co-transporters, type IIb sodium-dependent phosphate co-transporter (NaPi-IIb), inorganic phosphate transporter 1 (PiT-1) and inorganic phosphate transporter 2 (PiT-2) in the small intestine of broilers, 450 1-d-old Arbor Acres male broilers were randomly allocated to one of three treatments with ten replicate cages of fifteen birds per cage for each treatment in a completely randomised design. Chickens were fed a diet with no added inorganic P (containing 0·06 % non-phytate P (NPP)) or with either 0·21 or 0·44 % NPP for 21 d. Plasma P concentration in the hepatic portal vein, mRNA and protein expression levels of NaPi-IIb, PiT-1 and PiT-2 were determined at 7, 14 and 21 d of age. The results showed that the concentration of P in plasma in the hepatic portal vein increased as dietary NPP increased (P<0·0001). At 14 and 21 d of age, the increase in dietary NPP inhibited (P<0·003)NaPi-IIbmRNA expression level in the duodenum, as well as PiT-1 mRNA and protein expression levels in the ileum, but promoted NaPi-IIb protein expression level (P<0·002) and PiT-2 mRNA and protein expression levels (P<0·04) in the duodenum. These results suggest that NaPi-IIb, PiT-1 and PiT-2 might be important P transporters in the small intestine of broilers. Higher intestinal P absorption may be achieved by up-regulating the protein expression levels of NaPi-IIb and PiT-2 and down-regulating the protein expression of PiT-1.
Maternal vitamin D concentrations are associated with faster childhood reaction time and response speed, but not with motor fluency and flexibility, at the age of 5–6 years: the Amsterdam Born Children and their Development (ABCD) Study
Authors: Brouwer-Brolsma Elske M. , Vrijkotte Tanja G. M. , Feskens Edith J. M.
Published: May 2018

About 57 % of the pregnant European women have 25-hydroxyvitamin D (25(OH)D) concentrations below 50 nmol/l. However, as data on the impact of gestational vitamin D deficiency on maternal and fetal health are limited, the WHO does not advocate vitamin D supplementation as part of routine antenatal care. We explored associations between first trimester maternal 25(OH)D status and childhood cognition at 5–6 years of age (n1854, primarily Caucasian). Median serum 25(OH)D was determined at 13 (interquartile range 12–14) weeks of gestation. Childhood attention, motor fluency and flexibility and executive function were assessed using the Amsterdam Neuropsychological Tasks. Restricted cubic splines and linear regression analyses were used to analyse the data while adjusting for many maternal and child related covariates. Higher 25(OH)D status (nmol/l) was associated with better attention and executive functioning as shown by a faster reaction time (β−0·30 (sd0·14) ms,P=0·03), faster response speed (β−0·58 (sd0·21) ms,P=0·006), and better response speed stability (β−0·45 (sd0·17) ms,P=0·009). No associations were observed of serum 25(OH)D with motor fluency and flexibility. Associations were most pronounced among children of African origin (n205) as compared with those of Caucasian or another origin, for example attention (reaction time,β−2·06 (sd0·70) ms,P=0·004) and executive function (response speed,β−1·95 (sd0·94) ms,P=0·04). Concluding, maternal 25(OH)D status was significantly associated with childhood attention and executive function, while no associations were observed for 25(OH)D status with motor fluency and flexibility.
IM-sgi: an interface model for shape grammar implementations
Authors: Tching Joana , Reis Joaquim , Paio Alexandra
Published: May 2018

Information technologies are a driving force for progress in the design field, allowing new modes of creativity. However, most of the existing computational design tools are focused on the latest stages of the design process and especially directed to drafting operations. Conceptual design tools that support the designer in the creative and inventive early stages of the design project are still in their early development. Shape grammars (SG) were introduced by George Stiny in the 1970s, allowing the generation of designs according to a set of predefined rules. SG computational implementations have the potential to answer the need for tools that can assist designers, architects, and artists in the creative process, offering design alternatives, stimulating new ideas and encouraging the search for new design generation processes. Acknowledging this potential, a user-friendly interface seems essential for the adoption of these tools. Taking Scott Chase's interaction model as background, the aim of the present investigation is to define guidelines and begin to design a graphical-user interface for SG implementations. Inspection methods of human–computer interaction (HCI) were used to analyze existing SG implementations and understand usability issues. Subsequently, HCI ergonomic criteria for interface evaluation were adapted to establish guidelines for the design of an SG implementation interface, called IM-sqi. These guidelines take into account different user groups, adjustable interaction modes for each user group, and the nature of each task performed by the user.
Molecular detection of Anaplasma phagocytophilum DNA in the lesser horseshoe bat (Rhinolophus hipposideros) guano
Authors: Afonso E. , Goydadin A.-C.
Published: May 2018

Although bats are increasingly recognised as potential reservoir hosts of human zoonotic pathogens, bacteria in bats are still poorly studied. To investigate the DNA faecal prevalence of the bacterium Anaplasma phagocytophilum, we sampled 23 lesser horseshoe bat (Rhinolophus hipposideros) maternity colonies located in buildings (churches, barns) in rural villages of eastern France. A total of 552 faecal samples were collected from 278 individuals. Anaplasma phagocytophilum DNA was detected in the faeces of 63 individuals (22.7%). Such high prevalence might suggest persistent infection in bats and/or a frequent consumption of insect preys carrying bacteria. Faecal DNA prevalence varied highly among colonies but was not related to the colony size. Faecal DNA prevalence was the highest in the Jura Department, where the density of ticks is known to be the highest across the study area. Because the sampled bats live in close proximity to humans, we discuss how concerning the presence of A. phagocytophilum DNA in bat guano is for humans frequenting places of worship that shelter bats. We also advocate future research to understand what a high faecal DNA prevalence in bat guano really implicates in terms of bacteria transmission.
Positive predictive value of infective endocarditis in the Danish National Patient Registry: a validation study
Authors: Østergaard Lauge , Adelborg Kasper , Sundbøll Jens , Pedersen Lars , Loldrup Fosbøl Emil , Schmidt Morten
Published: May 2018

The positive predictive value of an infective endocarditis diagnosis is approximately 80% in the Danish National Patient Registry. However, since infective endocarditis is a heterogeneous disease implying long-term intravenous treatment, we hypothesiszed that the positive predictive value varies by length of hospital stay. A total of 100 patients with first-time infective endocarditis in the Danish National Patient Registry were identified from January 2010 – December 2012 at the University hospital of Aarhus and regional hospitals of Herning and Randers. Medical records were reviewed. We calculated the positive predictive value according to admission length, and separately for patients with a cardiac implantable electronic device and a prosthetic heart valve using the Wilson score method. Among the 92 medical records available for review, the majority of the patients had admission length ⩾2 weeks. The positive predictive value increased with length of admission. In patients with admission length <2 weeks the positive predictive value was 65% while it was 90% for admission length ⩾2 weeks. The positive predictive value was 81% for patients with a cardiac implantable electronic device and 87% for patients with a prosthetic valve. The positive predictive value of the infective endocarditis diagnosis in the Danish National Patient Registry is high for patients with admission length ⩾2 weeks. Using this algorithm, the Danish National Patient Registry provides a valid source for identifying infective endocarditis for research.
Regulations on Genome Editing of Human Embryos in Japan: Our Moral Moratorium
Authors: NAKAZAWA EISUKE , YAMAMOTO KEIICHIRO , AKABAYASHI ARU , AKABAYASHI AKIRA
Published: May 2018

The use of human embryos in genome editing research has recently been approved in China and the United Kingdom. In Japan, the debate on regulations on genome editing research studies using human embryos is underway, but is becoming increasingly entangled, to the point of deadlock. One main reason for this is the misalignment between the Japanese government and the research communities, in their awareness surrounding these regulations. In this article, we report on this ongoing and entangled debate in Japan concerning the regulations on genome editing technology using human embryos. The most critically needed next step is a grassroots level discussion among various experts such as those in the arts and humanities.
A Life Fulfilled: Should There Be Assisted Suicide for Those Who Are Done with Living?
Authors: BUIJSEN MARTIN
Published: May 2018

The issue of assisted suicide for those with a “fulfilled life” is being hotly debated in the Netherlands. A large number of Dutch people feel that elderly people (i.e., people who have reached the age of 70) with a “fulfilled life” should have access to assisted suicide. Citizens have therefore requested Parliament to expand the existing legislation that governs euthanasia and physician-assisted suicide. The Dutch constitution does not permit national legislation to be incompatible with higher international (human rights) law. An analysis of the case law of the European Court of Human Rights shows that a person’s right to decide on the time and manner of his or her death should be regarded as an aspect of the right to privacy. Although no positive obligation has been imposed on parties to the European Convention for the Protection of Human Rights and Fundamental Freedoms to facilitate suicide, they may do so, provided that certain conditions are met.
Quality of Living and Dying: Pediatric Palliative Care and End-of-Life Decisions in the Netherlands
Authors: BROUWER MARIJE , MAECKELBERGHE ELS , DE WEERD WILLEMIEN , VERHAGEN EDUARD
Published: May 2018

In 2002, The Netherlands continued its leadership in developing rules and jurisdiction regarding euthanasia and end-of-life decisions by implementing the Euthanasia Act, which allows euthanasia for patients 12 years of age and older. Subsequently, in 2005, the regulation on active ending of life for newborns was issued. However, more and more physicians and parents have stated that the age gap between these two regulations—children between 1 and 12 years old—is undesirable. These children should have the same right to end their suffering as adults and newborn infants. An extended debate on pediatric euthanasia ensued, and currently the debate is ongoing as to whether legislation should be altered in order to allow pediatric euthanasia. An emerging major question regards the active ending of life in the context of palliative care: How does a request for active ending of life relate to the care that is given to children in the palliative phase? Until now, the distinction between palliative care and end-of-life decisions continues to remain unclear, making any discussion about their mutual in- and exclusiveness hazardous at best. In this report, therefore, we aim to provide insight into the relationship between pediatric palliative care and end-of-life decisions, as understood in the Netherlands. We do so by first providing an overview of the (legal) rules and regulations regarding euthanasia and active ending of life, followed by an analysis of the relationship between these two, using the Dutch National Guidelines for Palliative Care for Children. The results of this analysis revealed two major and related features of palliative care and end-of-life decisions for children: (1) palliative care and end-of-life decisions are part of the same process, one that focuses both on quality of living and quality of dying, and (2) although physicians are seen as ultimately responsible for making end-of-life decisions, the involvement of parents and children in this decision is of the utmost importance and should be regarded as such.
Determination of Death in Execution by Lethal Injection in China
Authors: PAUL NORBERT W. , CAPLAN ARTHUR , SHAPIRO MICHAEL E. , ELS CHARL , ALLISON KIRK C. , LI HUIGE
Published: May 2018

Since 1997, execution in China has been increasingly performed by lethal injection. The current criteria for determination of death for execution by lethal injection (cessation of heartbeat, cessation of respiration, and dilated pupils) neither conform to current medical science nor to any standard of medical ethics. In practice, death is pronounced in China within tens of seconds after starting the lethal injection. At this stage, however, neither the common criteria for cardiopulmonary death (irreversible cessation of heartbeat and breathing) nor that of brain death (irreversible cessation of brain functions) have been met. To declare a still-living person dead is incompatible with human dignity, regardless of the processes following death pronouncement. This ethical concern is further aggravated if organs are procured from the prisoners. Analysis of postmortem blood thiopental level data from the United States indicates that thiopental, as used, may not provide sufficient surgical anesthesia. The dose of thiopental used in China is kept secret. It cannot be excluded that some of the organ explantation surgeries on prisoners subjected to lethal injection are performed under insufficient anesthesia in China. In such cases, the inmate may potentially experience asphyxiation and pain. Yet this can be easily overlooked by the medical professionals performing the explantation surgery because pancuronium prevents muscle responses to pain, resulting in an extremely inhumane situation. We call for an immediate revision of the death determination criteria in execution by lethal injection in China. Biological death must be ensured before death pronouncement, regardless of whether organ procurement is involved or not.
ON SEMIGROUPS WITH PSPACE-COMPLETE SUBPOWER MEMBERSHIP PROBLEM
Authors: STEINDL MARKUS
Published: May 2018

Fix a finite semigroup$S$and let$a_{1},\ldots ,a_{k},b$be tuples in a direct power$S^{n}$. The subpower membership problem (SMP) for$S$asks whether$b$can be generated by$a_{1},\ldots ,a_{k}$. For combinatorial Rees matrix semigroups we establish a dichotomy result: if the corresponding matrix is of a certain form, then theSMPis in P; otherwise it is NP-complete. For combinatorial Rees matrix semigroups with adjoined identity, we obtain a trichotomy: theSMPis either in P, NP-complete, or PSPACE-complete. This result yields various semigroups with PSPACE-completeSMPincluding the six-element Brandt monoid, the full transformation semigroup on three or more letters, and semigroups of all$n$by$n$matrices over a field for$n\geq 2$.
Die neuen Wechsler: WPPSI-IV und WISC-V
Authors: Daseking Monika , Petermann Franz
Published: May 2018

Zusammenfassung. Intelligenztests werden regelmäßig überarbeitet, um Leistungen von Testpersonen reliabel und valide einschätzen zu können. Die Veränderungen, die in den aktuellen Versionen der Wechsler-Tests für das Kindes- und Jugendalter (WPPSI-IV, WISC-V) umgesetzt wurden, bilden den aktuellen Forschungsstand zur Intelligenzdiagnostik ab. Aus Validierungsstudien mit spezifischen Stichproben und Fragestellungen können Testanwender wichtige Informationen zur Interpretation von Testergebnissen ziehen.
Dry‐Season Greening and Water Stress in Amazonia: The Role of Modeling Leaf Phenology
Authors: Manoli Gabriele , Ivanov Valeriy Y. , Fatichi Simone
Published: May 2018

Large uncertainties on the sensitivity of Amazon forests to drought exist. Even though water stress should suppress photosynthesis and enhance tree mortality, a green‐up has been often observed during the dry season. This interplay between climatic forcing and forest phenology is poorly understood and inadequately represented in most of existing dynamic global vegetation models calling for an improved description of the Amazon seasonal dynamics. Recent findings on tropical leaf phenology are incorporated in the state‐of‐the‐art eco‐hydrological model Thetys & Chloris. The new model accounts for a mechanistic light‐controlled leaf development, synchronized dry‐season litterfall, and an age‐dependent leaf photosynthetic capacity. Simulation results from 32 sites in the Amazon basin over a 15‐year period successfully mimic the seasonality of gross primary productivity; evapotranspiration (ET); as well as leaf area index, leaf age, and leaf productivity. Representation of tropical leaf phenology reproduces the observed dry‐season greening, reduces simulated gross primary productivity, and does not alter ET, when compared with simulations without phenology. Tolerance to dry periods, with the exception of major drought events, is simulated by the model. Deep roots rather than leaf area index regulation mechanisms control the response to short‐term droughts, but legacy effects can exacerbate multiyear water stress. Our results provide a novel mechanistic approach to model leaf phenology and flux seasonality in the tropics, reconciling the generally observed dry‐season greening, ET seasonality, and decreased carbon uptake during severe droughts.
Nitrogen Budget and Topographic Controls on Nitrous Oxide in a Shale‐Based Watershed
Authors: Weitzman Julie N. , Kaye Jason P.
Published: May 2018

The high spatial and temporal variabilities of nitrous oxide (N2O) emissions from the soil surface have made it difficult to predict flux patterns at the ecosystem scale, leading to imbalances in nitrogen (N) budgets at all scales. Our research sought to quantify topographic controls on the sources or sinks of N2O in the soil profile to improve our ability to predict soil‐atmosphere N2O fluxes and their contribution to watershed N budgets. We monitored surface‐to‐atmosphere N2O fluxes for 2 years in the Susquehanna Shale Hills Critical Zone Observatory in central Pennsylvania. Topographically convergent flow path locations had significantly higher surface N2O flux rates than nonconvergent flow path locations in the summer, but not other seasons. Overall, N2O fluxes were a large percentage (~19%) of total ecosystem N losses, and nearly twice as large as stream N export. Surface N2O fluxes were better correlated with concentrations of O2, N2O, and NO3−in shallow soil layers (<30 cm) than deeper soils. Following decades of anthropogenic atmospheric deposition and additional N from shale weathering, watershed N inputs (~8 kgN ha−1 yr−1) are greater than outputs (~3.7 kgN ha−1 yr−1). Our research revealed patterns of N cycling that are distinct from many other watersheds that have been extensively studied to understand N saturation; despite showing no other symptoms of N saturation, the watershed had high upland N2O losses, especially in convergent flow paths during summer. High upland N gas losses may be a mechanism that maintains N limitation to biota in the Shale Hills catchment.
Stratification Effects on Flow Hydrodynamics and Mixing at a Confluence With a Highly Discordant Bed and a Relatively Low Velocity Ratio
Authors: Cheng Zhengyang , Constantinescu George
Published: May 2018

The effects of temperature induced stratification on flow hydrodynamics, thermal mixing, and the capacity of the flow to entrain sediment at a medium‐size stream confluence with a highly discordant bed are investigated. To isolate the effects due to differences in the temperature/density of the incoming streams, two simulations were conducted with identical flow conditions (mean velocity ratio = 0.41 and temperature difference between the two streams ΔT = 4.7°C). In the first case the Richardson number was Ri = 0 (no coupling between the temperature and the momentum equations via the Boussinesq approximation), while in the second simulation Ri = 0.67. Even in the Ri = 0 case the structure of the mixing interface (MI) was different from the one expected for concordant bed confluences with a similar confluence angle and velocity ratio. The MI contained only corotating eddies shed in the shear layer forming on the fast‐speed side of the confluence apex. In the Ri = 0.67 case no wake region was present but a large recirculation eddy formed not far from the confluence apex. In both cases, the flow near the upstream part of the MI was found to be highly 3‐D and to allow the passage of particles from one side of the confluence to the other. While in the Ri = 0 case mixing was driven by the MI eddies, in the Ri = 0.67 case mixing was controlled by large near‐bed intrusions of heavier fluid from the tributary containing colder water and also by the fluid advected in and out of the recirculation eddy.
An Adaptive Multiphysics Model Coupling Vertical Equilibrium and Full Multidimensions for Multiphase Flow in Porous Media
Authors: Becker Beatrix , Guo Bo , Bandilla Karl , Celia Michael A. , Flemisch Bernd , Helmig Rainer
Published: May 2018

Efficient multiphysics (or hybrid) models that can adapt to the varying complexity of physical processes in space and time are desirable for modeling fluid migration in the subsurface. Vertical equilibrium (VE) models are simplified mathematical models that are computationally efficient but rely on the assumption of instant gravity segregation of the two phases, which may not be valid at all times or at all locations in the domain. Here we present a multiphysics model that couples a VE model to a full multidimensional model that has no reduction in dimensionality. We develop a criterion that determines subdomains where the VE assumption is valid during simulation. The VE model is then adaptively applied in those subdomains, reducing the number of computational cells due to the reduction in dimensionality, while the rest of the domain is solved by the full multidimensional model. We analyze how the threshold parameter of the criterion influences accuracy and computational cost of the new multiphysics model and give recommendations for the choice of optimal threshold parameters. Finally, we use a test case of gas injection to show that the adaptive multiphysics model is much more computationally efficient than using the full multidimensional model in the entire domain, while maintaining much of the accuracy.
A Novel Way to Map Debris Thickness on Himalayan Glaciers
Authors: Cook Terri
Published: May 2018

By combining changes in elevation with other data, scientists have developed a method for estimating the thickness of debris covering glaciers on whose water more than 800 million people depend.
Seismic and Geologic Evidence of Water‐Induced Earthquakes in the Three Gorges Reservoir Region of China
Authors: Huang Rong , Zhu Lupei , Encarnacion John , Xu Yixian , Tang Chi‐Chia , Luo Song , Jiang Xiaohuan
Published: May 2018

Earthquakes induced by reservoir impoundment pose great risk to property and lives worldwide, but studies demonstrating relationships between reservoir water levels, specific faults, and the local geology are rare. Here we show that the 2013M 5.1 Badong Earthquake, the largest earthquake so far in the Three Gorges Reservoir (TGR) region of China, occurred at a shallow depth on a right‐lateral south‐dipping strike‐slip fault. The fault is at least 15 km long and intercepts the TGR at the NS‐running Shennongxi River. We find that the earthquake and its foreshocks and aftershocks are confined to a fractured Triassic carbonate formation that crops out in the reservoir. The precise locations of earthquakes coupled with the local geology suggest that the sequence was induced by high pore pressure due to reservoir water infiltration in a specific rock type. The newly identified fault has the potential to generate earthquakes of magnitude approaching the designed seismic intensity limit of the Three Gorges Dam.
Reconciling Atmospheric and Oceanic Views of the Transient Climate Response to Emissions
Authors: Katavouta Anna , Williams Richard G. , Goodwin Philip , Roussenov Vassil
Published: May 2018

The Transient Climate Response to Emissions (TCRE), the ratio of surface warming and cumulative carbon emissions, is controlled by a product of thermal and carbon contributions. The carbon contribution involves the airborne fraction and the ratio of ocean saturated and atmospheric carbon inventories, with this ratio controlled by ocean carbonate chemistry. The evolution of the carbon contribution to the TCRE is illustrated in a hierarchy of models: a box model of the atmosphere‐ocean and an Earth system model, both integrated for 1,000 years, and a suite of Earth system models integrated for 140 years. For all models, there is the same generic carbonate chemistry response: An acidifying ocean during emissions leads to a decrease in the ratio of the ocean saturated and atmospheric carbon inventories and the carbon contribution to the TCRE. Hence, ocean carbonate chemistry is important in controlling the magnitude of the TCRE and its evolution in time.
On the Cause of Recent Variations in Lower Stratospheric Ozone
Authors: Chipperfield Martyn P. , Dhomse Sandip , Hossaini Ryan , Feng Wuhu , Santee Michelle L. , Weber Mark , Burrows John P. , Wild Jeanette D. , Loyola Diego , Coldewey‐Egbers Melanie
Published: May 2018

We use height‐resolved and total column satellite observations and 3‐D chemical transport model simulations to study stratospheric ozone variations during 1998–2017 as ozone‐depleting substances decline. In 2017 extrapolar lower stratospheric ozone displayed a strong positive anomaly following much lower values in 2016. This points to large interannual variability rather than an ongoing downward trend, as reported recently by Ball et al. (2018, https://doi.org/10.5194/acp‐18‐1379‐2018). The observed ozone variations are well captured by the chemical transport model throughout the stratosphere and are largely driven by meteorology. Model sensitivity experiments show that the contribution of past trends in short‐lived chlorine species to the ozone changes is small. Similarly, the potential impact of modest trends in natural brominated short‐lived species is small. These results confirm the important role that atmospheric dynamics plays in controlling ozone in the extrapolar lower stratosphere on multiannual time scales and the continued importance of monitoring ozone profiles as the stratosphere changes.
A 500‐Year Tree Ring‐Based Reconstruction of Extreme Cold‐Season Precipitation and Number of Atmospheric River Landfalls Across the Southwestern United States
Authors: Steinschneider Scott , Ho Michelle , Williams A. Park , Cook Edward R. , Lall Upmanu
Published: May 2018

This study develops a reconstruction of the frequency of extreme cold‐season precipitation and the occurrence of landfalling atmospheric river (AR) storm tracks across the southwestern Unites States using a network of tree ring chronologies and the Living Blended Drought Atlas (LBDA), a 500‐year tree ring based reconstruction of the summer Palmer Drought Severity Index. The first two rotated empirical orthogonal functions of the LBDA across the Southwest are shown to relate well to previously identified patterns of regional AR activity. Accordingly, the rotated empirical orthogonal functions also record patterns of extreme precipitation associated with those ARs, albeit with some uncertainty introduced by nonextreme precipitation. A network of chronologies sensitive to cold‐season precipitation is then used to reconstruct the occurrence of landfalling ARs and extreme precipitation along the southern Californian coast, demonstrating for the first time the feasibility of reconstructing AR landfalls and extreme events in the Southwest based on spatial patterns in a network of dendroclimatic proxies.
Composite regulation of ERK activity dynamics underlying tumour-specific traits in the intestine
Authors: Muta Yu , Fujita Yoshihisa , Sumiyama Kenta , Sakurai Atsuro , Taketo M. Mark , Chiba Tsutomu , Seno Hiroshi , Aoki Kazuhiro , Matsuda Michiyuki , Imajo Masamichi
Published: May 2018

Acting downstream of many growth factors, extracellular signal-regulated kinase (ERK) plays a pivotal role in regulating cell proliferation and tumorigenesis, where its spatiotemporal dynamics, as well as its strength, determine cellular responses. Here, we uncover the ERK activity dynamics in intestinal epithelial cells (IECs) and their association with tumour characteristics. Intravital imaging identifies two distinct modes of ERK activity, sustained and pulse-like activity, in IECs. The sustained and pulse-like activities depend on ErbB2 and EGFR, respectively. Notably, activation of Wnt signalling, the earliest event in intestinal tumorigenesis, augments EGFR signalling and increases the frequency of ERK activity pulses through controlling the expression of EGFR and its regulators, rendering IECs sensitive to EGFR inhibition. Furthermore, the increased pulse frequency is correlated with increased cell proliferation. Thus, ERK activity dynamics are defined by composite inputs from EGFR and ErbB2 signalling in IECs and their alterations might underlie tumour-specific sensitivity to pharmacological EGFR inhibition.
A data-driven, knowledge-based approach to biomarker discovery: application to circulating microRNA markers of colorectal cancer prognosis
Authors: Vafaee Fatemeh , Diakos Connie , Kirschner Michaela B. , Reid Glen , Michael Michael Z. , Horvath Lisa G. , Alinejad-Rokny Hamid , Cheng Zhangkai Jason , Kuncic Zdenka , Clarke Stephen
Published: May 2018

Recent advances in high-throughput technologies have provided an unprecedented opportunity to identify molecular markers of disease processes. This plethora of complex-omics data has simultaneously complicated the problem of extracting meaningful molecular signatures and opened up new opportunities for more sophisticated integrative and holistic approaches. In this era, effective integration of data-driven and knowledge-based approaches for biomarker identification has been recognised as key to improving the identification of high-performance biomarkers, and necessary for translational applications. Here, we have evaluated the role of circulating microRNA as a means of predicting the prognosis of patients with colorectal cancer, which is the second leading cause of cancer-related death worldwide. We have developed a multi-objective optimisation method that effectively integrates a data-driven approach with the knowledge obtained from the microRNA-mediated regulatory network to identify robust plasma microRNA signatures which are reliable in terms of predictive power as well as functional relevance. The proposed multi-objective framework has the capacity to adjust for conflicting biomarker objectives and to incorporate heterogeneous information facilitating systems approaches to biomarker discovery. We have found a prognostic signature of colorectal cancer comprising 11 circulating microRNAs. The identified signature predicts the patients’ survival outcome and targets pathways underlying colorectal cancer progression. The altered expression of the identified microRNAs was confirmed in an independent public data set of plasma samples of patients in early stage vs advanced colorectal cancer. Furthermore, the generality of the proposed method was demonstrated across three publicly available miRNA data sets associated with biomarker studies in other diseases.
Rapid Crop Cover Mapping for the Conterminous United States
Authors: Dahal Devendra , Wylie Bruce , Howard Danny
Published: May 2018

Timely crop cover maps with sufficient resolution are important components to various environmental planning and research applications. Through the modification and use of a previously developed crop classification model (CCM), which was originally developed to generate historical annual crop cover maps, we hypothesized that such crop cover maps could be generated rapidly during the growing season. Through a process of incrementally removing weekly and monthly independent variables from the CCM and implementing a ‘two model mapping’ approach, we found it viable to generate conterminous United States-wide rapid crop cover maps at a resolution of 250 m for the current year by the month of September. In this approach, we divided the CCM model into one ‘crop type model’ to handle the classification of nine specific crops and a second, binary model to classify the presence or absence of ‘other’ crops. Under the two model mapping approach, the training errors were 0.8% and 1.5% for the crop type and binary model, respectively, while test errors were 5.5% and 6.4%, respectively. With spatial mapping accuracies for annual maps reaching upwards of 70%, this approach demonstrated a strong potential for generating rapid crop cover maps by the 1st of September.
Reducing sitting time versus adding exercise: differential effects on biomarkers of endothelial dysfunction and metabolic risk
Authors: Duvivier Bernard M. F. M. , Bolijn Johanne E. , Koster Annemarie , Schalkwijk Casper G. , Savelberg Hans H. C. M. , Schaper Nicolaas C.
Published: May 2018

Recent studies suggest that substituting sitting with light physical activity has beneficial metabolic effects, but it is unclear if this is associated with parallel changes in endothelial function. Data from three randomized cross-over studies were analyzed, in which 61 subjects (with normal weight, overweight and type 2 diabetes) followed different activity regimens (Sit, SitLess and/or Exercise) of four days each. Subjects were instructed to sit 14 h/day (‘Sit’), to substitute 1 h/day of sitting with moderate-to-vigorous cycling (‘Exercise’) or to substitute 5–6 h/day sitting with light-intensity walking and standing (‘SitLess’). Physical activity was assessed 24 h/day by accelerometry (ActivPAL) and diet was standardized. Fasted circulating biomarkers of endothelial dysfunction, lipids and insulin sensitivity were assessed the morning after each activity regimen. The endothelial dysfunction score (ED-score) was computed by averaging the Z-scores of the circulating biomarkers of endothelial dysfunction. Compared to Sit, Exercise resulted in lower ED-score, sICAM1 and sE-selectin (p < 0.05), while no significant changes were observed after SitLess. The ED-score, sVCAM1 and sE-selectin were lower after Exercise compared to SitLess (p < 0.05). In contrast, compared to Sit, insulin sensitivity (HOMA2-IR) and plasma lipids (HDL-cholesterol, non-HDL-cholesterol, total cholesterol and Apo B) did not change significantly after Exercise but were improved after SitLess (p < 0.05). In conclusion, light physical activity and moderate-to-vigorous physical activity had a differential effect on risk markers of cardio-metabolic health and suggest the need of both performing structured exercise as well as reducing sitting time on a daily basis.
Prediction of sarcopenia using a combination of multiple serum biomarkers
Authors: Kwak Ju Yeon , Hwang Hyeoncheol , Kim Seon-Kyu , Choi Jeong Yi , Lee Seung-Min , Bang Hyun , Kwon Eun-Soo , Lee Kwang-Pyo , Chung Sun Gun , Kwon Ki-Sun
Published: May 2018

Sarcopenia is a gradual loss of skeletal muscle mass and function with aging. Given that sarcopenia has been recognized as a disease entity, effective molecular biomarkers for early diagnosis are required. We recruited 46 normal subjects and 50 patients with moderate sarcopenia aged 60 years and older. Sarcopenia was clinically identified on the basis of the appendicular skeletal muscle index by applying cutoff values derived from the Asian Working Group for Sarcopenia. The serum levels of 21 potential biomarkers were analyzed and statistically examined. Interleukin 6, secreted protein acidic and rich in cysteine, macrophage migration inhibitory factor, and insulin-like growth factor 1 levels differed significantly between the normal and sarcopenia groups. However, in each case, the area under the receiver operating characteristics curve (AUC) was <0.7. Subsequent combination of the measurements of these biomarkers into a single risk score based on logistic regression coefficients enhanced the accuracy of diagnosis, yielding an AUC value of 0.763. The best cutoff value of 1.529 had 70.0% sensitivity and 78.3% specificity (95% CI = 2.80–21.69, p < 0.0001). Combined use of the selected biomarkers provides higher diagnostic accuracy than individual biomarkers, and may be effectively utilized for early diagnosis and prognosis of sarcopenia.
Molecular basis of resistance to the microtubule-depolymerizing antitumor compound plocabulin
Authors: Pantazopoulou Areti , Galmarini Carlos María , Peñalva Miguel A.
Published: May 2018

Plocabulin (PM060184) is a microtubule depolymerizing agent with potent antiproliferative activity undergoing phase II clinical trials for the treatment of solid tumors. Plocabulin shows antifungal activity virtually abolishing growth of the filamentous fungus Aspergillus nidulans. A. nidulans hyphae depend both on mitotic and interphase microtubules, as human cells. Here, we exploited the A. nidulans genetic amenability to gain insight into the mechanism of action of plocabulin. By combining mutations in the two A. nidulans β-tubulin isotypes we obtained a plocabulin-insensitive strain, showing that β-tubulin is the only molecular target of plocabulin in fungal cells. From a genetic screen, we recovered five mutants that show plocabulin resistance but do not carry mutations in β-tubulin. Resistance mutations resulted in amino acid substitutions in (1) two subunits of the eukaryotic translation initiation factor eIF2B activating the General Amino Acid Control, (2) TIM44, an essential component of the inner mitochondrial membrane translocase, (3) two transcription factors of the binuclear zinc cluster family potentially interfering with the uptake or efflux of plocabulin. Given the conservation of some of the identified proteins and their respective cellular functions in the tumor environment, our results pinpoint candidates to be tested as potential biomarkers for determination of drug efficiency.
Accelerating polygon beam with peculiar features
Authors: Fang Zhao-Xiang , Zhao Hong-Ze , Chen Yue , Lu Rong-De , He Li-Qun , Wang Pei
Published: May 2018

We report on a novel kind of accelerating beams that follow parabolic paths in free space. In fact, this accelerating peculiar polygon beam (APPB) is induced by the spectral phase symmetrization of the regular polygon beam (RPB) with five intensity peaks, and it preserves a peculiar symmetric structure during propagation. Specially, such beam not only exhibits autofocusing property, but also possesses two types of accelerating intensity maxima, i.e., the cusp and spot-like structure, which does not exist in the previously reported accelerating beams with a single kind of lobes. We also provide a detailed insight into the theoretical origin and characteristics of this spatially accelerating beam through catastrophe theory. Moreover, an experimental scheme based on a digital micromirror device (DMD) with the binary spectral hologram is proposed to generate the target beam by precise modulation, and a longitudinal needle-like focus is observed around the focal region. The experimental results confirm the peculiar features presented in the theoretical findings. Further, the APPB is verified to exhibit self-healing property during propagation with either obstructed cusp or spot reconstructing after a certain distance. Hence, we believe that the APPB will facilitate the applications in the areas of particle manipulation, material processing and optofludics.
Localization and Speciation of Chromium in Coptis chinensis Franch. using Synchrotron Radiation X-ray Technology and Laser Ablation ICP-MS
Authors: Huang Wenli , Jiao Jie , Ru Mei , Bai Zhenqing , Yuan Honglin , Bao Zhian , Liang Zongsuo
Published: May 2018

Coptis chinensis Franch. is one of the most important medicinal plants globally. However, this species contains relatively high concentrations of chromium (Cr) which potentially detrimental to human health. It is important to understand Cr localization and speciation in order to evaluate its accumulation and transportation mechanisms and minimize Cr transfer to humans. As little previous work in this area has been carried out, we utilized synchrotron radiation microscopic X-ray fluorescence (SR-μXRF) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to spatially locate Cr, X-ray absorption near-edge spectroscopy (XANES) to analyze Cr speciation, and inductively coupled plasma mass spectrometry (ICP-MS) to detect Cr subcellular concentration. Micromapping results showed that Cr was distributed predominantly within the vascular cylinder, the periderm and some outer cortex, and the cortex and some vascular bundles in root, rhizome, and petiole, respectively. XANES data showed that Cr(VI) can be reduced to Cr(III) when grown with Cr(VI), and yielded a novel conclusion that this plant contain elemental chromium. ICP-MS data showed that Cr was primarily compartmentalized in cell walls in all tissues. The new insights on Cr accumulation in C. chinensis Franch. provide a theoretical basis for the evaluation of Cr in other medicinal plants.
Effects of Aging on the Obstacle Negotiation Strategy while Stepping over Multiple Obstacles
Authors: Chien Jung Hung , Post Jerod , Siu Ka-Chun
Published: May 2018

Forty-seven percent of falling accidents in older adults are caused by tripping over obstacles. Understanding what strategies are involved in obstacle negotiation in older adults could reduce fall risks. There is a paucity of research investigating how healthy adults negotiate multiple obstacles, which may better reflect the complexity of the real environment. The presence of a second obstacle has induced mixed results in the obstacle negotiation of healthy older adults with the interval between obstacles two steps apart. This study extended the knowledge to understand what strategies healthy younger and older adults used to step over two obstacles placed at three-step-length apart. Twenty healthy subjects performed 2 tasks: level ground walking and stepping over two obstacles. The height of each obstacle was set at 10% of subjects’ leg height. We found that aging significantly increased the toe clearance in leading and trailing legs when stepping over the obstacles at a three-step-length interval. Toe clearance was higher while stepping over the second obstacle than the first one in older adults. These results had two-fold meanings: the three-step-length interval was long enough to trigger the adjustment of the obstacle negotiation strategy, and aging led older adults to use conservative negotiation strategies.
Prior activity of olfactory receptor neurons is required for proper sensory processing and behavior in Drosophila larvae
Authors: Utashiro Nao , Williams Claire R. , Parrish Jay Z. , Emoto Kazuo
Published: May 2018

Animal responses to their environment rely on activation of sensory neurons by external stimuli. In many sensory systems, however, neurons display basal activity prior to the external stimuli. This prior activity is thought to modulate neural functions, yet its impact on animal behavior remains elusive. Here, we reveal a potential role for prior activity in olfactory receptor neurons (ORNs) in shaping larval olfactory behavior. We show that prior activity in larval ORNs is mediated by the olfactory receptor complex (OR complex). Mutations ofOrco, an odorant co-receptor required for OR complex function, cause reduced attractive behavior in response to optogenetic activation of ORNs. Calcium imaging reveals thatOrcomutant ORNs fully respond to optogenetic stimulation but exhibit altered temporal patterns of neural responses. These findings together suggest a critical role for prior activity in information processing upon ORN activation inDrosophilalarvae, which in turn contributes to olfactory behavior control.
First characterization of a microsporidial triosephosphate isomerase and the biochemical mechanisms of its inactivation to propose a new druggable target
Authors: García-Torres Itzhel , De la Mora-De la Mora Ignacio , Hernández-Alcántara Gloria , Molina-Ortiz Dora , Caballero-Salazar Silvia , Olivos-García Alfonso , Nava Gabriela , López-Velázquez Gabriel , Enríquez-Flores Sergio
Published: May 2018

The microsporidia are a large group of intracellular parasites with a broad range of hosts, including humans. Encephalitozoon intestinalis is the second microsporidia species most frequently associated with gastrointestinal disease in humans, especially immunocompromised or immunosuppressed individuals, including children and the elderly. The prevalence reported worldwide in these groups ranges from 0 to 60%. Currently, albendazole is most commonly used to treat microsporidiosis caused by Encephalitozoon species. However, the results of treatment are variable, and relapse can occur. Consequently, efforts are being directed toward identifying more effective drugs for treating microsporidiosis, and the study of new molecular targets appears promising. These parasites lack mitochondria, and oxidative phosphorylation therefore does not occur, which suggests the enzymes involved in glycolysis as potential drug targets. Here, we have for the first time characterized the glycolytic enzyme triosephosphate isomerase of E. intestinalis at the functional and structural levels. Our results demonstrate the mechanisms of inactivation of this enzyme by thiol-reactive compounds. The most striking result of this study is the demonstration that established safe drugs such as omeprazole, rabeprazole and sulbutiamine can effectively inactivate this microsporidial enzyme and might be considered as potential drugs for treating this important disease.
Factors associated with late presentation for HIV care in a single Belgian reference center: 2006–2017
Authors: Darcis Gilles , Lambert Iseult , Sauvage Anne-Sophie , Frippiat Frédéric , Meuris Christelle , Uurlings Françoise , Lecomte Marianne , Léonard Philippe , Giot Jean-Baptiste , Fombellida Karine , Vaira Dolores , Moutschen Michel
Published: May 2018

Late presentation for HIV care is a major issue and the cause of higher morbidity, mortality and transmission. In this regard, we analyzed the characteristics of patients presenting for care at our center from January 2006 to July 2017 (n = 687). The majority of the studied population was of African origin (54.3%) with heterosexual women representing the main group (n = 292; 42.5%). 44% of the patients were late presenters (LP) (presenting for care with CD4 T cells <350/mm3 or an AIDS defining event) and 24% were late presenters with advanced disease (LP-AD) (presenting for care with CD4 T cells <200/mm3 or an AIDS defining event). A very high risk of being LP and LP-AD was associated with Sub-Saharan origin (OR 3.4 and 2.6 respectively). Other factors independently associated with LP or LP-AD were age (OR 1.3), male gender (OR 2.0 and 1.5 respectively) and heterosexual route of transmission (OR 2.4 and 2.3 respectively). A significant increase in HIV screening without forgetting those groups would contribute to earlier HIV diagnosis, a key element to end the HIV epidemic. To achieve this goal, addressing the specific hurdles to HIV testing in the migrant population is critical.