bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal screening for Down syndrome in twin pregnancies: Estimates of screening performance based on 61 affected and 7302 unaffected twin pregnancies
Authors: Wald Nicholas J. , Bestwick Jonathan P. , Huttly Wayne J. , Aldis Jonathan , Borrell Antoni , Goodburn Sandy , Mills Ian 
Published: October 2018

AbstractThe aims of this study were to determine whether assumptions used in prenatal screening for Down syndrome in twin pregnancies are valid and derive estimates of risk and screening performance in twin pregnancies using observed data. Data were collected on nuchal translucency, chorionicity, pregnancy associated plasma protein‐A (PAPP‐A), and free ß human chorionic gonadotrophin (free ß‐hCG) from 61 twin pregnancies with Down syndrome and 7302 unaffected twin pregnancies. Distribution parameters were determined and used to estimate screening performance. The assumption that proportional differences in serum marker levels in affected and unaffected singleton pregnancies apply to twin pregnancies was not confirmed. Median free β‐hCG value in monochorionic affected twin pregnancies (2.63 multiples of the median [MoM]; 95% CI, 1.79‐3.22 MoM) was lower than that assuming proportionality (3.76 MoM), and the median PAPP‐A value in dichorionic affected twin pregnancies (1.88 MoM; 95% CI, 1.60‐2.17 MoM) was higher than that based on proportionality (1.33 MoM). The detection rate was 87% for a 3% false‐positive rate in monochorionic twin pregnancies and 74% in dichorionic twin pregnancies compared with 86% in singleton pregnancies. Estimates of screening performance in Down syndrome twin pregnancies do not need to rely on assumptions and can take account of chorionicity and gestational age.
Sulforaphane promotes chlamydial infection by suppressing mitochondrial protein oxidation and activation of complement C3
Authors: Saez Daniel , Dushime Rosine , Wu Hanzhi , Ramos Cordova Lourdes B. , Shukla Kirtikar , Brown‐Harding Heather , Furdui Cristina M. , Tsang Allen W. 
Published: October 2018

AbstractSulforaphane (SFN), a phytochemical found in broccoli and other cruciferous vegetables, is a potent antioxidant and anti‐inflammatory agent with reported effects in cancer chemoprevention and suppression of infection with intracellular pathogens. Here we report on the impact of SFN on infection with Chlamydia trachomatis (Ct), a common sexually transmitted pathogen responsible for 131 million new cases annually worldwide. Astoundingly, we find that SFN as well as broccoli sprouts extract (BSE) promote Ct infection of human host cells. Both the number and size of Ct inclusions were increased when host cells were pretreated with SFN or BSE. The initial investigations presented here point to both the antioxidant and thiol alkylating properties of SFN as regulators of Ct infection. SFN decreased mitochondrial protein sulfenylation and promoted Ct development, which were both reversed by treatment with mitochondria‐targeted paraquat (MitoPQ). Inhibition of the complement component 3 (complement C3) by SFN was also identified as a mechanism by which SFN promotes Ct infections. Mass spectrometry analysis found alkylation of cysteine 1010 (Cys1010) in complement C3 by SFN. The studies reported here raise awareness of the Ct infection promoting activity of SFN, and also identify potential mechanisms underlying this activity.
Glutamate dehydrogenase: Structure of a hyperinsulinism mutant, corrections to the atomic model, and insights into a regulatory site
Authors: Nassar Omneya M. , Li Changhong , Stanley Charles A. , Pettitt B. Montgomery , Smith Thomas J. 
Published: October 2018

AbstractMammalian glutamate dehydrogenase (GDH) has complex allosteric regulation and the loss of GTP inhibition causes the hyperinsulinism/hyperammonemia syndrome (HHS) where insulin is hypersecreted upon consumption of protein. The archetypical HHS lesion is H454Y and lies in the GTP binding pocket. To better understand the mechanism of HHS, we determined the crystal structure of H454Y. When the bovine GDH crystal structures were minimized to prepare for further computational analysis, unusually large deviations were found at the allosteric NADH binding site due to chemical sequence errors. Notably, 387 lies in an allosteric where several activators and inhibitors bind and should be lysine rather than asparagine. All structures were re‐refined and the consequence of this sequence error on NADH binding was calculated using free energy perturbation. The binding free energy penalty going from the correct to incorrect sequence found is +5 kcal/mol per site and therefore has a significant impact on drug development.Broader Audience AbstractGlutamate dehydrogenase is a key enzyme involved in amino acid catabolism. As such, it is heavily regulated in animals by a wide array of metabolites. The importance of this regulation is most apparent in a genetic disorder called hyperinsulinism/hyperammonemia (HHS) where patients hypersecrete insulin upon the consumption of protein. We determined the atomic structure of one of these HHS mutants to better understand the disease and also analyzed an allosteric regulatory site.
Computational investigation of the conformational dynamics in Tom20‐mitochondrial presequence tethered complexes
Authors: Srivastava Arpita , Tama Florence , Kohda Daisuke , Miyashita Osamu 
Published: October 2018

AbstractThe translocase of the outer membrane (TOM) mediates the membrane permeation of mitochondrial matrix proteins. Tom20 is a subunit of the TOM complex and binds to the N‐terminal region (ie, presequence) in mitochondrial matrix precursor proteins. Previous experimental studies indicated that the presequence recognition by Tom20 was achieved in a dynamic‐equilibrium among multiple bound states of the α‐helical presequence. Accordingly, the co‐crystallization of Tom20 and a presequence peptide required a disulfide‐bond cross‐linking. A 3‐residue spacer sequence (XAG) was inserted between the presequence and the anchoring Cys residue at the C‐terminus to not disturb the movement of the presequence peptide in the binding site of Tom20. Two crystalline forms were obtained according to Ala or Tyr at the X position of the spacer sequence, which may reflect the dynamic‐equilibrium of the presequence. Here, we have performed replica‐exchange molecular dynamics (REMD) simulations to study the effect of disulfide‐bond linker and single amino acid difference in the spacer region of the linker on the conformational dynamics of Tom20‐presequence complex. Free energy and network analyses of the REMD simulations were compared against previous simulations of non‐tethered system. We concluded that the disulfide‐bond tethering did not strongly affect the conformational ensemble of the presequence peptide in the complex. Further investigation showed that the choice of Ala or Tyr at the X position did not affect the most distributions of the conformational ensemble of the presequence. The present study provides a rational basis for the disulfide‐bond tethering to study the dynamics of weakly binding complexes.
Characterization of myofiber‐type‐specific molecules using mass spectrometry imaging
Authors: Goto‐Inoue Naoko , Morisasa Mizuki , Machida Kazumasa , Furuichi Yasuro , Fujii Nobuharu L. , Miura Shinji , Mori Tsukasa 
Published: October 2018

RationaleIn skeletal muscles, there are four myofiber types, Types I, IIa, IIx, and IIb, which show different contraction characteristics and have different metabolic statuses. To understand muscle function, it is necessary to analyze myofiber‐specific metabolic changes. However, these fibers are heterogeneous and are hard to discriminate by conventional analyses using tissue extracts. In this study, we found myofiber‐specific molecules and molecular markers of other cells such as smooth muscle cells, fat cells, and motor neurons, and visualized them within muscle sections.MethodsWe used three different muscle tissues, namely extensor digitorum longus, soleus, and gastrocnemius tissues, from ICR mice. After the muscles had been harvested, cross‐sections were prepared using a cryostat and analyzed using matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI), and conventional immunofluorescence imaging.ResultsBy comparing the MALDI MSI results with the immunofluorescence imaging results, we were able to identify each fiber and cell‐specific ion. It was especially important that we could find Type IIa and IIb specific ions, because these were difficult to distinguish.ConclusionsThrough MSI analyses, we performed a comprehensive survey to identify cell‐ and myofiber‐specific molecular markers. In conclusion, we assigned muscle fiber Type I, IIa, and IIb‐specific molecular ions at m/z 856.6, 872.6, and 683.8, respectively. These molecular markers might be useful for verifying changes that occur due to exercise and/or disease.
Fully autonomous micro air vehicle flight and landing on a moving target using visual–inertial estimation and model‐predictive control
Authors: Tzoumanikas Dimos , Li Wenbin , Grimm Marius , Zhang Ketao , Kovac Mirko , Leutenegger Stefan 
Published: October 2018

AbstractThe Mohamed Bin Zayed International Robotics Challenge (MBZIRC) held in spring 2017 was a very successful competition well attended by teams from all over the world. One of the challenges (Challenge 1) required an aerial robot to detect, follow, and land on a moving target in a fully autonomous fashion. In this paper, we present the hardware components of the micro air vehicle (MAV) we built with off the self components alongside the designed algorithms that were developed for the purposes of the competition. We tackle the challenge of landing on a moving target by adopting a generic approach, rather than following one that is tailored to the MBZIRC Challenge 1 setup, enabling easy adaptation to a wider range of applications and targets, even indoors, since we do not rely on availability of global positioning system. We evaluate our system in an uncontrolled outdoor environment where our MAV successfully and consistently lands on a target moving at a speed of up to 5.0 m/s.
The ETH‐MAV Team in the MBZ International Robotics Challenge
Authors: Bähnemann Rik , Pantic Michael , Popović Marija , Schindler Dominik , Tranzatto Marco , Kamel Mina , Grimm Marius , Widauer Jakob , Siegwart Roland , Nieto Juan 
Published: October 2018

AbstractThis study describes the hardware and software systems of the Micro Aerial Vehicle (MAV) platforms used by the ETH Zurich team in the 2017 Mohamed Bin Zayed International Robotics Challenge (MBZIRC). The aim was to develop robust outdoor platforms with the autonomous capabilities required for the competition, by applying and integrating knowledge from various fields, including computer vision, sensor fusion, optimal control, and probabilistic robotics. This paper presents the major components and structures of the system architectures and reports on experimental findings for the MAV‐based challenges in the competition. Main highlights include securing the second place both in the individual search, pick, and place the task of Challenge 3 and the Grand Challenge, with autonomous landing executed in less than 1 min and a visual servoing success rate of over for object pickups.
Force‐based perception and manipulation, the DTU team competing in MBZIRC 2017
Authors: Bilberg Christopher Prinds , Witting Christian Aamand , Andersen Nils Axel , Ravn Ole 
Published: October 2018

AbstractThis paper presents how the team from the Technical University of Denmark (DTU) implemented and solved the second challenge of the Mohamed Bin Zayed International Robotics Challenge. The competition was imitating a disaster scene where a robotic platform had to operate autonomously in a partly known environment to localize and manipulate a valve on a panel. To solve the given problem, the robot needs to be able to perceive the environment reliably. This is often accomplished using vision based solutions, however these might not always be feasible. Thus we show how force feedback can successfully be used as an alternative way of perception. To accomplish this the team equipped a robot arm with a force torque sensor, allowing the robot to perceive its environment through direct contact. This approach resulted in a robust solution of the task, independent of several external factors, such as lighting, which might affect a more traditional approach. First the theory and thoughts behind the implementation is presented, followed by an evaluation of the results from physical experiments and the competition itself, ultimately resulting in a robust solution which performed without errors in the competition.
Laboratory Insights Into the Effect of Sediment‐Hosted Methane Hydrate Morphology on Elastic Wave Velocity From Time‐Lapse 4‐D Synchrotron X‐Ray Computed Tomography
Authors: Sahoo Sourav K. , Madhusudhan B. N. , Marín‐Moreno Hector , North Laurence J. , Ahmed Sharif , Falcon‐Suarez Ismael Himar , Minshull Tim A. , Best Angus I. 
Published: October 2018

AbstractA better understanding of the effect of methane hydrate morphology and saturation on elastic wave velocity of hydrate‐bearing sediments is needed for improved seafloor hydrate resource and geohazard assessment. We conducted X‐ray synchrotron time‐lapse 4‐D imaging of methane hydrate evolution in Leighton Buzzard sand and compared the results to analogous hydrate formation and dissociation experiments in Berea sandstone, on which we measured ultrasonic P and S wave velocities and electrical resistivity. The imaging experiment showed that initially hydrate envelops gas bubbles and methane escapes from these bubbles via rupture of hydrate shells, leading to smaller bubbles. This process leads to a transition from pore‐floating to pore‐bridging hydrate morphology. Finally, pore‐bridging hydrate coalesces with that from adjacent pores creating an interpore hydrate framework that interlocks the sand grains. We also observed isolated pockets of gas within hydrate. We observed distinct changes in gradient of P and S wave velocities increase with hydrate saturation. Informed by a theoretical model of idealized hydrate morphology and its influence on elastic wave velocity, we were able to link velocity changes to hydrate morphology progression from initial pore‐floating, then pore‐bridging, to an interpore hydrate framework. The latter observation is the first evidence of this type of hydrate morphology and its measurable effect on velocity. We found anomalously low S wave velocity compared to the effective medium model, probably caused by the presence of a water film between hydrate and mineral grains.
On the Asymmetry Between Upward and Downward Field‐Aligned Currents Interacting With the Ionosphere
Authors: Streltsov A. V. 
Published: October 2018

AbstractThe paper presents results from the numerical study of the magnetosphere‐ionosphere interactions driven by the large‐scale electric field in the magnetically conjugate, high‐latitude regions of northern and southern hemispheres. Simulations of the two‐fluid MHD model demonstrate that these interactions can lead to a generation of a system of small‐scale, intense field‐aligned currents with a significant difference in size and amplitude between the upward and downward currents. In particular, in both hemispheres, the downward currents (where the electrons are flowing from the ionosphere) become more narrow and intense than the adjacent upward currents. At high latitudes, the field‐aligned currents are closely related to the discrete auroral arcs. The fact that this mechanism produces very narrow and intense downward currents embedded into the broader upward current regions makes it relevant to the explanation of the “black” auroral arcs appearing as narrow, dark strips embedded in the broad luminous background.
Empirical Modeling of Dayside Magnetic Structures Associated With Polar Cusps
Authors: Tsyganenko N. A. , Andreeva V. A. 
Published: October 2018

AbstractThe magnetic structure of dayside polar cusps is intimately related to the high‐latitude field‐aligned currents (FACs) and the cross‐B diamagnetic currents due to the penetrated plasma of magnetosheath origin. The dayside FAC configuration is sensitive to the azimuthal component of the interplanetary magnetic field, manifested in the latitudinal splitting and longitudinal overlapping of the Region 1 FAC zone around noon. The diamagnetism of the polar cusp plasma results in deep cleft‐shaped depressions of the ambient magnetic field. Neither of the above factors have yet been properly addressed in the existing empirical models of the distant magnetosphere. To fill this gap, an advanced data‐based model has been developed, including the spiral structure of the dayside FACs and their splitting/overlapping in response to the orientation and magnitude of the azimuthal interplanetary magnetic field component By. The cusp diamagnetic field depressions are modeled using a new approach, based on a 3‐D system of magnetic “bubbles” (Tsyganenko & Andreeva, 2018, https://doi.org/10.1029/2018GL078714). The magnetic effects associated with FACs and diamagnetic currents are represented within the framework of a single hybrid model, fitted to large subsets of spacecraft data. The obtained results are analyzed in the context of the dayside magnetic field response to interplanetary conditions and the geodipole tilt angle.
Current and Future Arctic Aerosols and Ozone From Remote Emissions and Emerging Local Sources—Modeled Source Contributions and Radiative Effects
Authors: Marelle L. , Raut J.‐C. , Law K. S. , Duclaux O. 
Published: October 2018

AbstractThe Arctic is influenced by air pollution transported from lower latitudes, and increasingly by local sources such as shipping and resource extraction. Local Arctic emissions could increase significantly in the future due to industrialization in a warming Arctic and further influence Arctic climate. We use the regional model Weather Research and Forecasting, including chemistry, to investigate current (2012) and future (2050) sources of Arctic aerosol and ozone pollution and their radiative impacts, focusing on spring and summer emissions from midlatitude anthropogenic sources, biomass burning, Arctic shipping, and Arctic gas flaring. Results show that remote anthropogenic and biomass burning emissions are likely to remain the main source of Arctic pollution burdens and of black carbon (BC) deposition over snow, and the main contributors to direct aerosol and ozone radiative effects in the Arctic. However, local Arctic flaring emissions are already a major source of BC in northwestern Russia, with a direct radiative effect of ∼25 mW/m2, and Arctic shipping is a strong current source of aerosols and ozone during summer in the Nordic Seas. We find that the direct effect of ozone and aerosols from summertime Arctic shipping is respectively negative (due to frequent temperature inversions) and positive (because of the high surface albedo) in our simulations, two new results. With the development of diversion shipping through the Arctic Ocean in summer 2050, Arctic shipping emissions could become the main source of surface aerosol and ozone pollution at the surface, with strong associated indirect effects of −0.8 W/m2, while flaring would remain an important BC source.
Seasonal Variations in High Arctic Free Tropospheric Aerosols Over Ny‐Ålesund, Svalbard, Observed by Ground‐Based Lidar
Authors: Shibata T. , Shiraishi K. , Shiobara M. , Iwasaki S. , Takano T. 
Published: October 2018

AbstractFree tropospheric aerosols over the high Arctic were observed by lidar for about 4 years from March 2014 at Ny‐Ålesund (78.9°N, 11.9°E). Vertical profiles of aerosol backscattering coefficients at two wavelengths, 532 and 1,064 nm, and depolarization ratio at one wavelength, 532 nm, are derived from these observations. The aerosol backscattering coefficient, the particle depolarization ratio, and the color ratio (the ratio of the backscattering coefficients at the two wavelengths) are roughly proportional to mass concentration, nonsphericity, and size of the aerosol particles, respectively. The aerosol backscattering coefficients indicate that monthly averaged concentration of aerosols was largest in the lowest free troposphere at about 1 km in altitude and was an order of magnitude less at an about 10 km in altitude and that the concentration of aerosols was highest from late spring to summer and lowest from late summer to fall. The depolarization ratio was less than a few percent in the troposphere during the four observed years. The depolarization ratio and the color ratio were greatest from winter to spring and smallest from summer to fall. The maxima in the monthly averaged nonsphericity and size precede the maxima in the monthly averaged concentration by a few months, indicating a seasonal change in the morphology or the characteristics of the aerosol particles. The small particle depolarization ratio of less than a few percent is consistent with previous findings that Arctic free tropospheric aerosol particles in spring are composed of a mixture of liquid phase sulfate and soot particles.
Holistic Assessment of SO2 Injections Using CESM1(WACCM): Introduction to the Special Issue
Authors: Kravitz Ben , MacMartin Douglas G. , Tilmes Simone , Richter Jadwiga H. , Mills Michael J. , Lamarque Jean‐Francois , Tribbia Joseph , Large William 
Published: October 2018

AbstractWe introduce a special issue on a holistic assessment of solar geoengineering via stratospheric SO2 injection in the state‐of‐the‐art climate model, Community Earth System Model, version 1 with the Whole Atmosphere Community Climate Model as its atmospheric component (CESM1(WACCM)). This model has numerous complexities that allow it to represent some of the most important nonlinearities associated with stratospheric SO2 injection, including aerosol microphysical growth and stratospheric chemistry. The studies described herein represent the steps toward and first attempt in a state‐of‐the‐art climate model to use solar geoengineering to meet multiple simultaneous objectives via SO2 injection at multiple locations. First, a set of simulations was carried out to better understand the response of the model to variations in latitude, altitude, and amount of sulfur dioxide injections. Subsequently, in a century‐long simulation, a feedback algorithm was employed to meet specific objectives and manage uncertainty, wherein the injection amount at each location was adjusted every model year. Most of the analyses contained in this special issue focus on surface climate and stratospheric changes in the simulations. In addition, 20 ensemble members of the feedback simulation have been carried out and provided to the community (the Geoengineering Large Ensemble) to expand the scope of analyses to low signal‐to‐noise ratio fields, including regional effects, impacts assessment, and extreme events. The demonstration provided by these simulations is a step toward understanding the space of achievable climate objectives via solar geoengineering or, phrased differently, determining what solar geoengineering can do and what it cannot do.
Cell cycle inhibitors protect motor neurons in an organoid model of Spinal Muscular Atrophy
Authors: Hor Jin Hui , Soh Eunice Shi-Yi , Tan Li Yi , Lim Valerie Jing Wen , Santosa Munirah Mohamad , Winanto  , Ho Beatrice Xuan , Fan Yong , Soh Boon-Seng , Ng Shi-Yan 
Published: October 2018

AbstractSpinal Muscular Atrophy (SMA) is caused by genetic mutations in the SMN1 gene, resulting in drastically reduced levels of Survival of Motor Neuron (SMN) protein. Although SMN is ubiquitously expressed, spinal motor neurons are one of the most affected cell types. Previous studies have identified pathways uniquely activated in SMA motor neurons, including a hyperactivated ER stress pathway, neuronal hyperexcitability, and defective spliceosomes. To investigate why motor neurons are more affected than other neural types, we developed a spinal organoid model of SMA. We demonstrate overt motor neuron degeneration in SMA spinal organoids, and this degeneration can be prevented using a small molecule inhibitor of CDK4/6, indicating that spinal organoids are an ideal platform for therapeutic discovery.