bluuebunny/crossref_metadata_2025 huggingface dataset:
Force and Position–Velocity Coordination for Delayed Bilateral Teleoperation of a Mobile Robot
Authors: Slawiñski E. , Moya V. , Santiago D. , Mut V.
Published: March 2019

This document proposes a control scheme for delayed bilateral teleoperation of a mobile robot, which it is sought to achieve a coordination of the master device position with the slave mobile robot velocity, and at the same time synchronize the force exerted by the operator with force applied by the environment over the mobile robot. This approach allows the operator to improve the sensitive perception of the remote environment in which the robot navigates while he generates commands to control the mobile robot motion. In this paper, variable and asymmetrical communication time delays are taken into account, as well as a non-passive model of the human operator, for which a novel model is proposed that has a more general structure than the typical ones used to date in the teleoperation field. Furthermore, based on the theoretical analysis presented, the state of convergence in the stationary response is obtained. In addition, an experimental performance evaluation is carried out, where the position–velocity error, force error and the time to complete the task are evaluated. In the tests, a human operator commands a remote mobile robot to push objects of different weight while he perceives the weight of each object through the force feedback system. As an outcome, the theoretical and practical results obtained allow concluding that a satisfactory trade-off between stability and transparency is reached.
Design Boundary Layer Thickness and Switching Gain in SMC Algorithm for AUV Motion Control
Authors: Taheri Ehsan , Ferdowsi Mohamad Hossein , Danesh Mohammad
Published: March 2019

Designing the boundary layer thickness and switching gain in the nonlinear part of sliding mode controller (SMC) is one of the main subjects in SMC design that needs human experience, knowledge on the amplitude of disturbances, and information about the bounds of system uncertainties. In this paper, to reduce the trial-and-error effort by the designer(s) two different fitness functions in the horizontal and vertical planes are presented and a heuristic method is used for their optimization. The optimal switching gain in the proposed approach properly compensates the unmodeled dynamics, model uncertainty, and external disturbances. Chattering phenomenon in control signals and noise measurement effect are reduced by the optimal selection of boundary layer thickness. This proposed method is applied to an autonomous underwater vehicle (AUV) and evaluated through the real-time and cost-effective manner. The execution code is implemented on a single-board computer (SBC) through the xPC Target and is evaluated by the processor-in-the-loop (PIL) test. The results of the PIL test in the two different test cases indicate that the chattering phenomenon and amplitude of control signal applied to the actuators are reduced in comparison with the three conventional approaches in the AUV motion control.
Neurocognitive SuperAging in Older Adults Living With HIV: Demographic, Neuromedical and Everyday Functioning Correlates
Authors: Saloner Rowan , Campbell Laura M. , Serrano Vanessa , Montoya Jessica L. , Pasipanodya Elizabeth , Paolillo Emily W. , Franklin Donald , Ellis Ronald J. , Letendre Scott L. , Collier Ann C. , Clifford David B. , Gelman Benjamin B. , Marra Christina M. , McCutchan J. Allen , Morgello Susan , Sacktor Ned , Jeste Dilip V. , Grant Igor , Heaton Robert K. , Moore David J. ,   the CHARTER and HNRP Groups
Published: March 2019

Objectives:Studies of neurocognitively elite older adults, termedSuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA.Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status.Results:Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA.Conclusions:Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019,25, 507–519)
Neuropsychological Function Response to Nocturnal Blue Light Blockage in Individuals With Symptoms of Insomnia: A Pilot Randomized Controlled Study
Authors: Zimmerman Molly E. , Kim Moosun Brad , Hale Christiane , Westwood Andrew J. , Brickman Adam M. , Shechter Ari
Published: March 2019

Objectives:Insomnia is associated with neuropsychological dysfunction. Evidence points to the role of nocturnal light exposure in disrupted sleep patterns, particularly blue light emitted through smartphones and computers used before bedtime. This study aimed to test whether blocking nocturnal blue light improves neuropsychological function in individuals with insomnia symptoms.Methods:This study used a randomized, placebo-controlled crossover design. Participants were randomly assigned to a 1-week intervention with amber lenses worn in wrap-around frames (to block blue light) or a 1-week intervention with clear lenses (control) and switched conditions after a 4-week washout period. Neuropsychological function was evaluated with tests from the NIH Toolbox Cognition Battery at three time points: (1) baseline (BL), (2) following the amber lenses intervention, and (3) following the clear lenses intervention. Within-subjects general linear models contrasted neuropsychological test performance following the amber lenses and clear lenses conditions with BL performance.Results:Fourteen participants (mean(standard deviation,SD): age = 46.5(11.4)) with symptoms of insomnia completed the protocol. Compared with BL, individuals performed better on the List Sorting Working Memory task after the amber lenses intervention, but similarly after the clear lenses intervention (F= 5.16;p= .014; η2= 0.301). A similar pattern emerged on the Pattern Comparison Processing Speed test (F= 7.65;p= 0.002; η2= 0.370). Consideration of intellectual ability indicated that treatment with amber lenses “normalized” performance on each test from approximately 1SDbelow expected performance to expected performance.Conclusions:Using a randomized, placebo-controlled crossover design, we demonstrated improvement in processing speed and working memory with a nocturnal blue light blocking intervention among individuals with insomnia symptoms. (JINS, 2019,25, 668–677)
MONETARY POLICY WHEN THE ZERO LOWER BOUND IS WITHIN REACH: A SMOOTH TRANSITION REGRESSION APPROACH
Authors: Steiner Andreas
Published: March 2019

The period of low interest rates since the global financial crisis provides a unique opportunity to examine monetary policy reaction functions near the zero lower bound (ZLB). Using smooth transition regressions for the Euro area and a panel of industrialized countries we show that central banks anticipate the ZLB by less aggressive policies in its vicinity while we do not find a significant difference between both regimes for the US.
Numeracy and Risk Literacy: What Have We Learned so Far?
Authors: Garcia-Retamero Rocio , Sobkow Agata , Petrova Dafina , Garrido Dunia , Traczyk Jakub
Published: March 2019

Numerical skills are essential to make informed decisions in our daily life. Unfortunately, many people lack basic numeracy, which limits their ability to accurately interpret risks (i.e., risk literacy). In this paper, we provide an overview of research investigating the role of numeracy in two prominent domains, where most research was concentrated, health and finance. We summarize what has been learned so far in these domains and suggest promising venues for future research. We conclude that it is important to conduct interventions to improve numeracy in less numerate individuals and to help them make informed decisions and achieve better life outcomes.
Wie interpretiere ich eine ABGA?
Authors: Nemec Marek
Published: March 2019

Zusammenfassung. Die arterielle Blutgasanalyse (ABGA) ist eine in vielen medizinischen Fachbereichen häufig benutzte diagnostische Methode. Sie liefert Einblicke in die metabolischen Prozesse und in den Gasaustausch des Patienten. Die korrekte Interpretation erfordert Kenntnisse über den klinischen Zustand des Patienten und das Grundprinzip der Säure-Basen-Regulation. Ein systematisches Vorgehen vereinfacht die Interpretation und ermöglicht es, gemischte Störungen besser zu erkennen. Eine mögliche Vorgehensweise anhand des physiologischen Modells wird in diesem Artikel vorgestellt.
CME: Nachkontrollen bei Schrittmacher-Patienten
Authors: Brenner Roman , Ammann Peter
Published: March 2019

Zusammenfassung. Hausärzte haben bei Patienten mit einem Herzschrittmacher (PM) eine zentrale Rolle, da sie häufig primärer Ansprechpartner bei Problemen im Zusammenhang mit dem PM sind. In der unmittelbaren postoperativen Periode sind eine akute Dyspnoe, Schwindel/Synkopen oder eine Wundinfektion Alarmsymptome und bedürfen einer raschen Abklärung. Spät nach Implantation eines PM sind die Symptome häufig weniger klar assoziiert mit dem PM. Zur Nachkontrolle bei PM-Patienten gehört die Inspektion der PM-Loge und ein Ruhe-EKG, das in Kenntnis der PM-Funktion und -Programmierung interpretiert werden muss. Meist wird zur Eingrenzung und Lösung des PM-Problems eine PM-Abfrage unumgänglich.
Makrohämaturie beim antikoagulierten Patienten
Authors: Kurz Michael
Published: March 2019

Zusammenfassung. Zusammenfassungen: Die Makrohämaturie sollte als Symptom immer abgeklärt werden, unabhängig davon, ob eine Antikoagulation besteht oder nicht. Die häufigsten Ursachen sind die hämorrhagische Zystitis und bei Männern die Prostatahyperplasie. Die wichtigsten weiteren Differenzialdiagnosen sind das Urothelkarzinom und die Urolithiasis. Zur Primärdiagnostik gehören ein Urinschnelltest, eine Urinkultur und die Sonografie des Harntrakts. Die vollständige Abklärung erfolgt mittels Zystoskopie und Computertomografie. Die Gerinnung sollte immer kontrolliert werden. Leichte Blutungen können ambulant urologisch abgeklärt werden, während Patienten mit hämodynamisch relevanten und/oder tamponierenden Hämorrhagien immer stationär aufgenommen werden sollten. Antikoagulierte, blutende Patienten erfordern auch wegen der internistischen Grunderkrankungen die volle Aufmerksamkeit von Urologen, Internisten und Anästhesisten.
Accelerated Contribution of the Paleo–Congo River to Global Seawater 87Sr/86Sr Change Following Eocene‐Oligocene Collapse of the African Surface
Authors: Linol Bastien , de Villiers Stephanie , de Wit Maarten
Published: March 2019

The thick Phanerozoic duricrust covering sub‐Saharan Africa collapsed about 40–30 million years ago (Ma) across what is now the Congo Basin, driving accelerated erosion and flushing of underlying red bed sediments into the South Atlantic Ocean. Investigated red beds, boulders of silcretes and calcretes exposed around the margins and in river systems of the Congo Basin have 87Sr/86Sr values between 0.73 and 0.75. Leaching experiments from these rocks and sediments also reveal high 87Sr/86Sr (0.72–0.73). This implies a greater radiogenic Sr flux from the paleo–Congo River compared to its modern value that is influenced to a greater degree now by weathering of carbonates and basalts with relatively low 87Sr/86Sr (0.70–0.71). Modeling of our data during the mid‐Cenozoic spill of the Congo Basin indicates that increased Sr river flux from the paleo‐Congo contributed significantly to the rapid changes of dissolved 87Sr/86Sr in the global ocean, complementing at that time a similar effect of increased carbonate weathering linked to the Himalayan‐Tibetan Orogeny.
Assessing Contributions of Major Emitters' Paris‐Era Decisions to Future Temperature Extremes
Authors: Lewis Sophie C. , Perkins‐Kirkpatrick Sarah E. , Althor Glenn , King Andrew D. , Kemp Luke
Published: March 2019

The likelihood and severity of high‐impact future temperature extremes can be reduced through climate change mitigation efforts. However, meeting the Paris Agreement warming limits requires notably stronger greenhouse gas emissions reduction efforts by major emitters than existing pledges. We examine the impact of Paris‐era decision‐making by the world's three largest greenhouse gas emitters (EU, USA, and China) on projected future extreme temperature events. Country‐level contributions to the occurrence of future temperature extremes are calculated based on current emissions policies and sequential mitigation efforts, using a new metric called the Contribution to Excess Risk Ratio. We demonstrate the Contribution concept by applying it to extreme monthly temperature projections. In many regions, future extremes depend on the current and future carbon dioxide emissions reductions adopted by major emitters. By implementing stronger Paris‐era climate pledges, major emitters can reduce the frequency of future extremes and their own calculated contributions to these temperature extremes.
Delayed Dynamic Triggering of Disposal‐Induced Earthquakes Observed by a Dense Array in Northern Oklahoma
Authors: Peña Castro A. F. , Dougherty S. L. , Harrington R. M. , Cochran E. S.
Published: March 2019

Recent increases in earthquake occurrence rates in Oklahoma have been linked to the injection of large volumes of saltwater, a byproduct of oil and gas extraction. Here we present a detailed study of remote earthquake triggering in an area of active injection‐induced seismicity in northern Oklahoma using data from the LArge‐n Seismic Survey in Oklahoma (LASSO) temporary array and nearby permanent broadband seismic stations. We estimate changes in earthquake rates and calculate the Coulomb failure stress changes on potential receiver faults due to passing teleseismic surface waves. A statistically significant increase in seismicity is observed ∼8 hr after the 16 April 2016 Mw 7.8 Ecuador earthquake. The Coulomb stress changes associated with the Ecuador earthquake are on the order of ∼1 kPa. Physical mechanisms consistent with the observed dynamic stress threshold include failure driven by activation of aseismic slip or hydrological response of the fault system.
Effects of Partial Cloudiness in a Cloud Microphysics Scheme on Simulated Precipitation Processes During a Boreal Summer
Authors: Kim So‐Young , Bae Soo Ya , Park Rae‐Seol , Hong Song‐You
Published: March 2019

The effect of partial cloudiness is included in a cloud microphysics scheme, and its impact on precipitation processes is examined through global‐model simulations for a boreal summer. An excessive precipitation rate in the simulations is reduced by considering the partial cloudiness effect in microphysical processes, especially in the tropical western Pacific region where convective activity is strong. The reduction of the precipitation rate in this region is mainly due to a decrease in convective precipitation, as the partial cloudiness effect in cloud microphysical processes modulates the convective activity by interacting with radiative processes. Cloud radiative forcings are weaker in the simulations including the partial cloudiness effect, as more cloud water and ice are converted to rain and snow mainly due to enhanced accretion rates. This leads to a decrease in cloud radiative forcing for both shortwave and longwave fluxes, which is overestimated overall over the ocean in the simulations. Temperature is lowered overall as increased longwave radiative cooling overcompensates increased shortwave radiative heating. This reduces the convective available potential energy and results in a decrease in convective precipitation. The weakened instability and upward motion over the tropical western Pacific region due to the partial cloudiness effect not only affect the local precipitation processes in this region but also suppress the downward motion over the tropical eastern Pacific regions by modulating the large‐scale zonal circulation over the tropical Pacific ocean.
The Sensitivity of the Jet Stream Response to Climate Change to Radiative Assumptions
Authors: Tan Zhihong , Lachmy Orli , Shaw Tiffany A.
Published: March 2019

Comprehensive climate models exhibit a large spread in the magnitude of projected poleward eddy‐driven jet shift in response to warming. The spread has been connected to the radiative response to warming. To understand how different radiative assumptions alone affect the jet shift in response to warming, we introduce a new clear‐sky longwave radiation hierarchy that spans idealized (gray versus four bands; without or with interactive water vapor) through comprehensive (correlated‐k) radiation in the same general circulation model. The new hierarchy is used in an aquaplanet configuration to explore the impact of radiation on the jet stream response to warming, independent of mean surface temperature and meridional surface temperature gradient responses. The gray radiation scheme produces a split jet and its eddy‐driven jet shifts equatorward as climate warms, whereas the storm track shifts equatorward then poleward. Including four longwave bands leads to a merged jet that shifts slightly poleward with warming, and the storm track shifts monotonically poleward. Including interactive water vapor makes the poleward jet shift comparable to the jet shift with comprehensive radiation and interactive water vapor. These jet and storm track differences are linked to the radiation response of the stratospheric temperature, the tropopause height, and the meridional gradient of the radiative forcing to warming. Dynamically, the equatorward jet shift with the gray scheme is consistent with reduced wave reflection on the poleward flank of the jet, whereas the poleward jet shift with the other schemes is consistent with increased eddy length scale that favors equatorward wave propagation.
Three‐Dimensional Model of the Lithospheric Structure Under the Eastern Tibetan Plateau: Implications for the Active Tectonics and Seismic Hazards
Authors: Lu Renqi , Liu Yiduo , Xu Xiwei , Tan Xibin , He Dengfa , Yu Guihua , Cai Minggang , Wu Xiyan
Published: March 2019

Details of lithospheric structures in three‐dimensions (3‐D) are key to understanding the dynamics of crustal deformation and earthquakes in active orogenic systems. In this study, we develop a 3‐D model of the eastern Tibetan Plateau using the Skua‐Gocad software based on the latest Rayleigh wave tomography. We perform a quantitative modeling workflow to map the details of the Moho discontinuities and the high‐velocity anomalies. Then, we integrate the topography, major active faults, large earthquakes, and crustal Poisson's ratios to analyze the relationship between the shallow and deep structures of this region. Our study shows that the Moho is generally coupled with the topography. A steep Moho ramp exists under the plateau margin and its surface projection intersects the Longmen Shan (LMS) at a low oblique angle (~22°). Active deformation and large earthquakes are related to the steep Moho ramp under the plateau margin. Moreover, based on a 3‐D model of the Poisson's ratio perturbations, we find that deformation across the central LMS is characterized as a crocodile‐type wedge in the crust and lithospheric mantle, due to the resistance of the Yangtze craton and isostatic rebound. We suggest that a tectonic wedging model that contains both the upper‐crust thrusting and lower‐crustal thickening contribute to the LMS orogeny. Three‐dimensional visualization of the lithospheric structure is well suited to reveal the different levels of deformation and their relationships. Quantitative modeling methods provide effective constraints on the active blocks in the eastern Tibetan Plateau.
Seasonal and Interannual Patterns and Controls of Hydrological Fluxes in an Amazon Floodplain Lake With a Surface‐Subsurface Process Model
Authors: Ji Xinye , Lesack Lance F. W. , Melack John M. , Wang Shilong , Riley William J. , Shen Chaopeng
Published: March 2019

Floodplain lakes represent important aquatic ecosystems, and field‐based estimates of their water budgets are difficult to obtain, especially over multiple years. We examine the hydrological fluxes for an Amazon floodplain lake connected to the Solimões River using a process‐based hydrologic model. Water exchanges between the river and lake agree well with field estimates, including the timing of different hydrological phases. However, beyond available field data, modeling results show that the seven simulated years all differed from each other. These interannual differences were caused by the interplay between phases when water levels were rising with river‐water flowing into the lake (RWRI), versus rising with lake‐water flowing out to the river (RWLO). This exchange determines the river‐water content in the lake (CL). Maximum CL occurred before river levels peaked because local catchment contributions can be sufficient to push lake‐water out to the river, even as river levels rise. Numerical experiments show that the seasonal distribution of local rainfall, local catchment size, and interannual variability in both climate and river stage can contribute to differing dynamics of CL in a floodplain lake. Their impacts vary among phases: river‐rise dominates the RWRI, whereas local hydrological processes dominate the RWLO and receding‐water phases. Intermediate‐to‐long‐term rainfall accumulation controls CL during the RWLO phase, whereas annual precipitation accumulation is important for CL during low water. Our model generalizes beyond limited available field studies and offers potential to better understand floodplain lakes in other areas and how regional versus local changes in climate may affect their hydrological dynamics.
Spontaneous Emergence of Space Stems Ahead of Negative Leaders in Lightning and Long Sparks
Authors: Malagón‐Romero A. , Luque A.
Published: March 2019

We investigate the emergence of space stems ahead of negative leaders. These are luminous spots that appear ahead of an advancing leader mediating the leader's stepped propagation. We show that space stems start as regions of locally depleted conductivity that form in the streamers of the corona around the leader. An attachment instability enhances the electric field leading to strongly inhomogeneous, bright, and locally warmer regions ahead of the leader that explain the existing observations. Since the attachment instability is only triggered by fields above 10 kV/cm and internal electric fields are lower in positive than in negative streamers, our results explain why, although common in negative leaders, space stems, and stepping are hardly observed if not absent in positive leaders. Further work is required to fully explain the streamer to leader transition, which requires an electric current persisting for timescales longer than the typical attachment time of electrons, around 100 ns.
Do Surface and Air Temperatures Contain Similar Imprints of Evaporative Conditions?
Authors: Panwar Annu , Kleidon Axel , Renner Maik
Published: March 2019

Generally, surface and air temperatures seem closely related but we show that they respond differently to evaporative conditions. We evaluate the temperature increase in response to solar radiation for different evaporative fractions, using observations from the Southern Great Plains. The warming rate of air temperature decreases only by 1.7 × 10−3 K/(W m−2) from dry to moist conditions compared to a stronger reduction by 14 × 10−3 K/(W m−2) for surface temperature. The weaker response of air temperature to evaporative fraction is explained by the larger growth of boundary layer on drier days, which suppresses the warming of air. Estimates based on this explanation reproduce the warming rate of air temperature in observations. Our results show that diurnal variations of surface temperatures contain imprints of evapotranspiration while air temperatures do not. These findings appear important to be considered when using, analyzing, or interpreting temperature data in studies dealing with climate change, hydrology, or land‐atmosphere interactions.
Antibody–drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study
Authors: Trudel Suzanne , Lendvai Nikoletta , Popat Rakesh , Voorhees Peter M. , Reeves Brandi , Libby Edward N. , Richardson Paul G. , Hoos Axel , Gupta Ira , Bragulat Veronique , He Zangdong , Opalinska Joanna B. , Cohen Adam D.
Published: March 2019

Interim analyses of a phase I study with GSK2857916, an antibody–drug conjugate against B cell maturation antigen, have previously reported a 60% overall response and 7.9 months progression-free survival in relapsed/refractory multiple myeloma (MM). We provide updated safety and efficacy results of the BMA117159 trial following an additional 14 months' follow-up. This open-label, first-in-human, phase I study was conducted at nine centres in the USA, Canada and the UK, and included adults with MM and progressive disease after stem cell transplantation, alkylators, proteasome inhibitors, and immunomodulators. In part 1, the recommended dose of 3.4 mg/kg was identified; in part 2, patients received GSK2857916 3.4 mg/kg once every 3 weeks. Selected part 2 safety/tolerability and efficacy endpoints are reported. Twenty-one (60.0%; 95% confidence interval (CI) 42.1–76.1) of 35 patients achieved partial response or better, including two stringent complete responses and three complete responses. The median progression-free survival was 12 months and median duration of response was 14.3 months. Thrombocytopenia and corneal events were commonly reported; no new safety signals were identified. GSK2857916 was well tolerated and demonstrated a rapid, deep and durable response in heavily pre-treated patients with relapsed/refractory MM, consolidating the interim analyses conclusions that GSK2857916 is a promising treatment for these patients.
Cancer-associated fibroblasts enhance tumor-associated macrophages enrichment and suppress NK cells function in colorectal cancer
Authors: Zhang Rongsheng , Qi Fan , Zhao Fei , Li Geng , Shao Shengli , Zhang Xiaochao , Yuan Lifei , Feng Yongdong
Published: March 2019

Cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) are important components of the tumor microenvironment, which have been reported to localize in colorectal carcinomas where they promote tumor progression. One of the crucial effects they exerted is immune-suppression, which was reported recently, however, the overall mechanism has not been fully addressed. In this study, it was shown that TAMs were enriched in colorectal cancer, and their infiltration was associated with VCAM-1 expression. Human colorectal cancer-derived CAFs can promote the adhesion of monocytes by up-regulating VCAM-1 expression in colorectal cancer cells. Furthermore, CAFs can attract monocytes by secreting IL-8 rather than SDF-1 and subsequently promote M2 polarization of macrophages, which synergize with CAFs in suppressing the functioning of natural killer (NK) cells. It was also found that CAFs promoted M2 macrophages recruitment in tumor tissue in vivo, and after VCAM-1 knocking-down in tumor cells or depletion of macrophages, the pro-tumor effect of CAFs was partly abolished, but no change was observed in NK cells infiltration. Collectively, the findings in this work show that TAMs and CAFs function synergistically in the tumor microenvironment and have the capacity to regulate NK cells in colorectal cancer and this presents a novel mechanism.
The histone demethylase LSD1 promotes renal inflammation by mediating TLR4 signaling in hepatitis B virus-associated glomerulonephritis
Authors: Yang Yi-Tong , Wang Xuan , Zhang Yue-Yue , Yuan Wei-Jie
Published: March 2019

Renal inflammation significantly contributes to the progression of hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN), but the mechanisms that control its precise regulation remain largely unknown. In this study, we showed that the lysine-specific demethylase 1 (LSD1) was significantly upregulated in renal tissue of HBV-GN patients, and its expression was positively correlated with inflammation. Functionally, LSD1 could promote HBV-induced release of proinflammatory mediators in HK-2 cells, a human renal tubular epithelial (RTE) cell line. Mechanistic investigations suggested that LSD1 directly promoted the transcription of the inflammatory-related gene Tlr4 by eliminating the mono- or di-methylation of H3K9 near its promoter. Knockdown of Lsd1 further inhibited TLR4-NF-κB/JNK signaling cascades, and subsequently decreased HBV-induced production of proinflammatory mediators in HK-2 cells. Co-transfection with Tlr4-expressing plasmids counteracted these effects. Meanwhile, downregulation of abovementioned TLR4-related pathways using small-molecule inhibitors attenuated inflammation. Importantly, LSD1 inhibitor tranylcypromine (TCP) could inhibit TLR4-NF-κB/JNK signaling axis and alleviate renal inflammation in HBV transgenic mice. Taken together, our data identify LSD1 as a novel regulator of renal inflammation and as a potential therapeutic target in HBV-GN.
Synthetic control over orientational degeneracy of spacer cations enhances solar cell efficiency in two-dimensional perovskites
Authors: Hu Jun , Oswald Iain W. H. , Stuard Samuel J. , Nahid Masrur Morshed , Zhou Ninghao , Williams Olivia F. , Guo Zhenkun , Yan Liang , Hu Huamin , Chen Zheng , Xiao Xun , Lin Yun , Yang Zhibin , Huang Jinsong , Moran Andrew M. , Ade Harald , Neilson James R. , You Wei
Published: March 2019

Two-dimensional perovskites have emerged as more intrinsically stable materials for solar cells. Chemical tuning of spacer organic cations has attracted great interest due to their additional functionalities. However, how the chemical nature of the organic cations affects the properties of two-dimensional perovskites and devices is rarely reported. Here we demonstrate that the selection of spacer cations (i.e., selective fluorination of phenethylammonium) affects the film properties of two-dimensional perovskites, leading to different device performance of two-dimensional perovskite solar cells (average n = 4). Structural analysis reveals that different packing arrangements and orientational disorder of the spacer cations result in orientational degeneracy and different formation energies, largely explaining the difference in film properties. This work provides key missing information on how spacer cations exert influence on desirable electronic properties and device performance of two-dimensional perovskites via the weak and cooperative interactions of these cations in the crystal lattice.
Nonlinear magnetotransport shaped by Fermi surface topology and convexity
Authors: He Pan , Hsu Chuang-Han , Shi Shuyuan , Cai Kaiming , Wang Junyong , Wang Qisheng , Eda Goki , Lin Hsin , Pereira Vitor M. , Yang Hyunsoo
Published: March 2019

The nature of Fermi surface defines the physical properties of conductors and many physical phenomena can be traced to its shape. Although the recent discovery of a current-dependent nonlinear magnetoresistance in spin-polarized non-magnetic materials has attracted considerable attention in spintronics, correlations between this phenomenon and the underlying fermiology remain unexplored. Here, we report the observation of nonlinear magnetoresistance at room temperature in a semimetal WTe2, with an interesting temperature-driven inversion. Theoretical calculations reproduce the nonlinear transport measurements and allow us to attribute the inversion to temperature-induced changes in Fermi surface convexity. We also report a large anisotropy of nonlinear magnetoresistance in WTe2, due to its low symmetry of Fermi surfaces. The good agreement between experiments and theoretical modeling reveals the critical role of Fermi surface topology and convexity on the nonlinear magneto-response. These results lay a new path to explore ramifications of distinct fermiology for nonlinear transport in condensed-matter.
Deep-water circulation changes lead North Atlantic climate during deglaciation
Authors: Muschitiello Francesco , D’Andrea William J. , Schmittner Andreas , Heaton Timothy J. , Balascio Nicholas L. , deRoberts Nicole , Caffee Marc W. , Woodruff Thomas E. , Welten Kees C. , Skinner Luke C. , Simon Margit H. , Dokken Trond M.
Published: March 2019

Constraining the response time of the climate system to changes in North Atlantic Deep Water (NADW) formation is fundamental to improving climate and Atlantic Meridional Overturning Circulation predictability. Here we report a new synchronization of terrestrial, marine, and ice-core records, which allows the first quantitative determination of the response time of North Atlantic climate to changes in high-latitude NADW formation rate during the last deglaciation. Using a continuous record of deep water ventilation from the Nordic Seas, we identify a ∼400-year lead of changes in high-latitude NADW formation ahead of abrupt climate changes recorded in Greenland ice cores at the onset and end of the Younger Dryas stadial, which likely occurred in response to gradual changes in temperature- and wind-driven freshwater transport. We suggest that variations in Nordic Seas deep-water circulation are precursors to abrupt climate changes and that future model studies should address this phasing.
A global analysis of coral bleaching over the past two decades
Authors: Sully S. , Burkepile D. E. , Donovan M. K. , Hodgson G. , van Woesik R.
Published: March 2019

Thermal-stress events associated with climate change cause coral bleaching and mortality that threatens coral reefs globally. Yet coral bleaching patterns vary spatially and temporally. Here we synthesize field observations of coral bleaching at 3351 sites in 81 countries from 1998 to 2017 and use a suite of environmental covariates and temperature metrics to analyze bleaching patterns. Coral bleaching was most common in localities experiencing high intensity and high frequency thermal-stress anomalies. However, coral bleaching was significantly less common in localities with a high variance in sea-surface temperature (SST) anomalies. Geographically, the highest probability of coral bleaching occurred at tropical mid-latitude sites (15–20 degrees north and south of the Equator), despite similar thermal stress levels at equatorial sites. In the last decade, the onset of coral bleaching has occurred at significantly higher SSTs (∼0.5 °C) than in the previous decade, suggesting that thermally susceptible genotypes may have declined and/or adapted such that the remaining coral populations now have a higher thermal threshold for bleaching.
Coming together to define membrane contact sites
Authors: Scorrano Luca , De Matteis Maria Antonietta , Emr Scott , Giordano Francesca , Hajnóczky György , Kornmann Benoît , Lackner Laura L. , Levine Tim P. , Pellegrini Luca , Reinisch Karin , Rizzuto Rosario , Simmen Thomas , Stenmark Harald , Ungermann Christian , Schuldiner Maya
Published: March 2019

Close proximities between organelles have been described for decades. However, only recently a specific field dealing with organelle communication at membrane contact sites has gained wide acceptance, attracting scientists from multiple areas of cell biology. The diversity of approaches warrants a unified vocabulary for the field. Such definitions would facilitate laying the foundations of this field, streamlining communication and resolving semantic controversies. This opinion, written by a panel of experts in the field, aims to provide this burgeoning area with guidelines for the experimental definition and analysis of contact sites. It also includes suggestions on how to operationally and tractably measure and analyze them with the hope of ultimately facilitating knowledge production and dissemination within and outside the field of contact-site research.
ER stress-induced mediator C/EBP homologous protein thwarts effector T cell activity in tumors through T-bet repression
Authors: Cao Yu , Trillo-Tinoco Jimena , Sierra Rosa A. , Anadon Carmen , Dai Wenjie , Mohamed Eslam , Cen Ling , Costich Tara L. , Magliocco Anthony , Marchion Douglas , Klar Richard , Michel Sven , Jaschinski Frank , Reich Richard R. , Mehrotra Shikhar , Cubillos-Ruiz Juan R. , Munn David H. , Conejo-Garcia Jose R. , Rodriguez Paulo C.
Published: March 2019

Understanding the intrinsic mediators that render CD8+ T cells dysfunctional in the tumor microenvironment is a requirement to develop more effective cancer immunotherapies. Here, we report that C/EBP homologous protein (Chop), a downstream sensor of severe endoplasmic reticulum (ER) stress, is a major negative regulator of the effector function of tumor-reactive CD8+ T cells. Chop expression is increased in tumor-infiltrating CD8+ T cells, which correlates with poor clinical outcome in ovarian cancer patients. Deletion of Chop in T cells improves spontaneous antitumor CD8+ T cell immunity and boosts the efficacy of T cell-based immunotherapy. Mechanistically, Chop in CD8+ T cells is elevated primarily through the ER stress-associated kinase Perk and a subsequent induction of Atf4; and directly represses the expression of T-bet, a master regulator of effector T cell function. These findings demonstrate the primary role of Chop in tumor-induced CD8+ T cell dysfunction and the therapeutic potential of blocking Chop or ER stress to unleash T cell-mediated antitumor immunity.
Stronger influence of anthropogenic disturbance than climate change on century-scale compositional changes in northern forests
Authors: Danneyrolles Victor , Dupuis Sébastien , Fortin Gabriel , Leroyer Marie , de Römer André , Terrail Raphaële , Vellend Mark , Boucher Yan , Laflamme Jason , Bergeron Yves , Arseneault Dominique
Published: March 2019

Predicting future ecosystem dynamics depends critically on an improved understanding of how disturbances and climate change have driven long-term ecological changes in the past. Here we assembled a dataset of >100,000 tree species lists from the 19th century across a broad region (>130,000km2) in temperate eastern Canada, as well as recent forest inventories, to test the effects of changes in anthropogenic disturbance, temperature and moisture on forest dynamics. We evaluate changes in forest composition using four indices quantifying the affinities of co-occurring tree species with temperature, drought, light and disturbance. Land-use driven shifts favouring more disturbance-adapted tree species are far stronger than any effects ascribable to climate change, although the responses of species to disturbance are correlated with their expected responses to climate change. As such, anthropogenic and natural disturbances are expected to have large direct effects on forests and also indirect effects via altered responses to future climate change.
Functional interplay between TFIIH and KAT2A regulates higher-order chromatin structure and class II gene expression
Authors: Sandoz Jérémy , Nagy Zita , Catez Philippe , Caliskan Gizem , Geny Sylvain , Renaud Jean-Baptiste , Concordet Jean-Paul , Poterszman Arnaud , Tora Laszlo , Egly Jean-Marc , Le May Nicolas , Coin Frédéric
Published: March 2019

The TFIIH subunit XPB is involved in combined Xeroderma Pigmentosum and Cockayne syndrome (XP-B/CS). Our analyses reveal that XPB interacts functionally with KAT2A, a histone acetyltransferase (HAT) that belongs to the hSAGA and hATAC complexes. XPB interacts with KAT2A-containing complexes on chromatin and an XP-B/CS mutation specifically elicits KAT2A-mediated large-scale chromatin decondensation. In XP-B/CS cells, the abnormal recruitment of TFIIH and KAT2A to chromatin causes inappropriate acetylation of histone H3K9, leading to aberrant formation of transcription initiation complexes on the promoters of several hundred genes and their subsequent overexpression. Significantly, this cascade of events is similarly sensitive to KAT2A HAT inhibition or to the rescue with wild-type XPB. In agreement, the XP-B/CS mutation increases KAT2A HAT activity in vitro. Our results unveil a tight connection between TFIIH and KAT2A that controls higher-order chromatin structure and gene expression and provide new insights into transcriptional misregulation in a cancer-prone DNA repair-deficient disorder.
Gfi1b regulates the level of Wnt/β-catenin signaling in hematopoietic stem cells and megakaryocytes
Authors: Shooshtarizadeh Peiman , Helness Anne , Vadnais Charles , Brouwer Nelleke , Beauchemin Hugues , Chen Riyan , Bagci Halil , Staal Frank J. T. , Coté Jean-François , Möröy Tarik
Published: March 2019

Gfi1b is a transcriptional repressor expressed in hematopoietic stem cells (HSCs) and megakaryocytes (MKs). Gfi1b deficiency leads to expansion of both cell types and abrogates the ability of MKs to respond to integrin. Here we show that Gfi1b forms complexes with β-catenin, its co-factors Pontin52, CHD8, TLE3 and CtBP1 and regulates Wnt/β-catenin-dependent gene expression. In reporter assays, Gfi1b can activate TCF-dependent transcription and Wnt3a treatment enhances this activation. This requires interaction between Gfi1b and LSD1 and suggests that a tripartite β-catenin/Gfi1b/LSD1 complex exists, which regulates Wnt/β-catenin target genes. Consistently, numerous canonical Wnt/β-catenin target genes, co-occupied by Gfi1b, β-catenin and LSD1, have their expression deregulated in Gfi1b-deficient cells. When Gfi1b-deficient cells are treated with Wnt3a, their normal cellularity is restored and Gfi1b-deficient MKs regained their ability to spread on integrin substrates. This indicates that Gfi1b controls both the cellularity and functional integrity of HSCs and MKs by regulating Wnt/β-catenin signaling pathway.
Mechanical behaviour of fluid-lubricated faults
Authors: Cornelio C. , Spagnuolo E. , Di Toro G. , Nielsen S. , Violay M.
Published: March 2019

Fluids are pervasive in fault zones cutting the Earth's crust; however, the effect of fluid viscosity on fault mechanics is mainly conjectured by theoretical models. We present friction experiments performed on both dry and fluid-permeated silicate and carbonate bearing-rocks, at normal effective stresses up to 20 MPa, with a slip-rate ranging between 10 μm/s and 1 m/s. Four different fluid viscosities were tested. We show that both static and dynamic friction coefficients decrease with viscosity and that dynamic friction depends on the dimensionless Sommerfeld number (S) as predicted by the elastohydrodynamic-lubrication theory (EHD).Under favourable conditions (depending on the fluid viscosity (η), co-seismic slip-rate (V), fault geometry (L/H02) and earthquake nucleation depth (∝σeff)), EHD might be an effective weakening mechanism during natural and induced earthquakes. However, at seismic slip-rate, the slip weakening distance (Dc) increases markedly for a range of fluid viscosities expected in the Earth, potentially favouring slow-slip rather than rupture propagation for small to moderate earthquakes.
The conserved NxNNWHW motif in Aha-type co-chaperones modulates the kinetics of Hsp90 ATPase stimulation
Authors: Mercier Rebecca , Wolmarans Annemarie , Schubert Jonathan , Neuweiler Hannes , Johnson Jill L. , LaPointe Paul
Published: March 2019

Hsp90 is a dimeric molecular chaperone that is essential for the folding and activation of hundreds of client proteins. Co-chaperone proteins regulate the ATP-driven Hsp90 client activation cycle. Aha-type co-chaperones are the most potent stimulators of the Hsp90 ATPase activity but the relationship between ATPase regulation and in vivo activity is poorly understood. We report here that the most strongly conserved region of Aha-type co-chaperones, the N terminal NxNNWHW motif, modulates the apparent affinity of Hsp90 for nucleotide substrates. The ability of yeast Aha-type co-chaperones to act in vivo is ablated when the N terminal NxNNWHW motif is removed. This work suggests that nucleotide exchange during the Hsp90 functional cycle may be more important than rate of catalysis.
Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density
Authors: Ivarsdottir Erna V. , Benonisdottir Stefania , Thorleifsson Gudmar , Sulem Patrick , Oddsson Asmundur , Styrkarsdottir Unnur , Kristmundsdottir Snaedis , Arnadottir Gudny A. , Thorgeirsson Gudmundur , Jonsdottir Ingileif , Zoega Gunnar M. , Thorsteinsdottir Unnur , Gudbjartsson Daniel F. , Jonasson Fridbert , Holm Hilma , Stefansson Kari
Published: March 2019

The corneal endothelium is vital for transparency and proper hydration of the cornea. Here, we conduct a genome-wide association study of corneal endothelial cell density (cells/mm2), coefficient of cell size variation (CV), percentage of hexagonal cells (HEX) and central corneal thickness (CCT) in 6,125 Icelanders and find associations at 10 loci, including 7 novel. We assess the effects of these variants on various ocular biomechanics such as corneal hysteresis (CH), as well as eye diseases such as glaucoma and corneal dystrophies. Most notably, an intergenic variant close to ANAPC1 (rs78658973[A], frequency = 28.3%) strongly associates with decreased cell density and accounts for 24% of the population variance in cell density (β = −0.77 SD, P = 1.8 × 10−314) and associates with increased CH (β = 0.19 SD, P = 2.6 × 10−19) without affecting risk of corneal diseases and glaucoma. Our findings indicate that despite correlations between cell density and eye diseases, low cell density does not increase the risk of disease.
Multiple ABCB1 transcriptional fusions in drug resistant high-grade serous ovarian and breast cancer
Authors: Christie Elizabeth L. , Pattnaik Swetansu , Beach Jessica , Copeland Anthony , Rashoo Nineveh , Fereday Sian , Hendley Joy , Alsop Kathryn , Brady Samuel L. , Lamb Greg , Pandey Ahwan , deFazio Anna , Thorne Heather , Bild Andrea , Bowtell David D. L.
Published: March 2019

ABCB1 encodes Multidrug Resistance protein (MDR1), an ATP-binding cassette member involved in the cellular efflux of chemotherapeutic drugs. Here we report that ovarian and breast samples from chemotherapy treated patients are positive for multiple transcriptional fusions involving ABCB1, placing it under the control of a strong promoter while leaving its open reading frame intact. We identified 15 different transcriptional fusion partners involving ABCB1, as well as patients with multiple distinct fusion events. The partner gene selected depended on its structure, promoter strength, and chromosomal proximity to ABCB1. Fusion positivity was strongly associated with the number of lines of MDR1-substrate chemotherapy given. MDR1 inhibition in a fusion positive ovarian cancer cell line increased sensitivity to paclitaxel more than 50-fold. Convergent evolution of ABCB1 fusion is therefore frequent in chemotherapy resistant recurrent ovarian cancer. As most currently approved PARP inhibitors (PARPi) are MDR1 substrates, prior chemotherapy may precondition resistance to PARPi.