bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the Sustainability of Water Availability for the Water‐Food‐Energy‐Ecosystem Nexus in the Niger River Basin
Authors: Yang Jie , Yang Y. C. Ethan , Khan Hassaan F. , Xie Hua , Ringler Claudia , Ogilvie Andrew , Seidou Ousmane , Djibo Abdouramane Gado , van Weert Frank , Tharme Rebecca
Published: August 2018

Water, food, energy, and the ecosystems they depend on interact with each other in highly complex and interlinked ways. These interdependencies can be traced particularly well in the context of a river basin, which is delineated by hydrological boundaries. The interactions are shaped by humans interacting with nature, and as such, a river basin can be characterized as a complex, coupled socioecological system. The Niger River Basin in West Africa is such a system, where water infrastructure development to meet growing water, food, and energy demands may threaten a productive and vulnerable basin ecosystem. These dynamic interactions remain poorly understood. Trade‐off analyses between different sectors and at different spatial scales are needed to support solution‐oriented policy analysis, particularly in transboundary basins. This study assesses the impact of climate and human/anthropogenic changes on the water, energy, food, and ecosystem sectors and characterizes the resulting trade‐offs through a set of generic metrics related to the sustainability of water availability. Results suggest that dam development can mitigate negative impacts from climate change on hydropower generation and also on ecosystem health to some extent.
The Dependence of Solar Wind Burst Size on Burst Duration and Its Invariance Across Solar Cycles 23 and 24
Authors: Tindale E. , Chapman S.C. , Moloney N.R. , Watkins N.W.
Published: August 2018

Time series of solar wind variables are bursty in nature. Bursts, or excursions, in the time series of solar wind parameters are associated with various transient structures in the solar wind plasma and are often the drivers of increased space weather activity in Earth's magnetosphere. We define bursts by setting a threshold value of the time series and identifying how often, and for how long, it is exceeded. This allows us to study how the statistical distributions and scaling properties of burst parameters vary over solar cycles 23 and 24. We find that the distributions of burst duration and integrated burst size vary over the solar cycle and between the equivalent phases of consecutive cycles. However, there exists a single power law scaling relation between burst size and duration, with a joint area‐duration scaling exponentαthat is independent of the solar cycle. This provides a solar cycle invariant constraint between possible sizes and durations of solar wind bursts that can occur.
Spatial and Temporal Variations in Earthquake Stress Drop on Gofar Transform Fault, East Pacific Rise: Implications for Fault Strength
Authors: Moyer Pamela A. , Boettcher Margaret S. , McGuire Jeffery J. , Collins John A.
Published: August 2018

On Gofar Transform Fault on the East Pacific Rise, the largest earthquakes (6.0 ≤ MW ≤ 6.2) have repeatedly ruptured the same portion of the fault, while intervening fault segments host swarms of microearthquakes. These long‐term patterns in earthquake occurrence suggest that heterogeneous fault zone properties control earthquake behavior. Using waveforms from ocean bottom seismometers that recorded seismicity before and after an anticipated 2008 MW 6.0 mainshock, we investigate the role that differences in material properties have on earthquake rupture at Gofar. We determine stress drop for 138 earthquakes (2.3 ≤ MW ≤ 4.0) that occurred within and between the rupture areas of large earthquakes. Stress drops are calculated from corner frequencies derived using an empirical Green's function spectral ratio method, and seismic moments are obtained by fitting the omega‐square source model to the low frequency amplitude of the displacement spectrum. Our analysis yields stress drops from 0.04 to 3.2 MPa with statistically significant spatial variation, including ~2 times higher average stress drop in fault segments where large earthquakes also occur compared to fault segments that host earthquake swarms. We find an inverse correlation between stress drop and P wave velocity reduction, which we interpret as the effect of fault zone damage on the ability of the fault to store strain energy that leads to our spatial variations in stress drop. Additionally, we observe lower stress drops following the MW 6.0 mainshock, consistent with increased damage and decreased fault strength after a large earthquake.
Background Free‐Tropospheric Ice Nucleating Particle Concentrations at Mixed‐Phase Cloud Conditions
Authors: Lacher Larissa , DeMott Paul J. , Levin Ezra J. T. , Suski Kaitlyn J. , Boose Yvonne , Zipori Assaf , Herrmann Erik , Bukowiecki Nicolas , Steinbacher Martin , Gute Ellen , Abbatt Jonathan P. D. , Lohmann Ulrike , Kanji Zamin A.
Published: August 2018

Clouds containing ice are vital for precipitation formation and are important in determining the Earth's radiative budget. However, primary formation of ice in clouds is not fully understood. In the presence of ice nucleating particles (INPs), the phase change to ice is promoted, but identification and quantification of INPs in a natural environment remains challenging because of their low numbers. In this paper, we quantify INP number concentrations in the free troposphere (FT) as measured at the High Altitude Research Station Jungfraujoch (JFJ), during the winter, spring, and summer of the years 2014–2017. INPs were measured at conditions relevant for mixed‐phase cloud formation at T = 241/242 K. To date, this is the longest timeline of semiregular measurements akin to online INP monitoring at this site and sampling conditions. We find that INP concentrations in the background FT are on average capped at 10/stdL (liter of air at standard conditions [T = 273 K and p = 1013 hPa]) with an interquartile range of 0.4–9.6/stdL, as compared to measurements during times when other air mass origins (e.g., Sahara or marine boundary layer) prevailed. Elevated concentrations were measured in the field campaigns of 2016, which might be due to enhanced influence from Saharan dust and marine boundary layer air arriving at the JFJ. The upper limit of INP concentrations in the background FT is supported by measurements performed at similar conditions, but at different locations in the FT, where we find INP concentrations to be below 13/stdL most of the time.
Influence of Wind Direction on Thermodynamic Properties and Arctic Mixed‐Phase Clouds in Autumn at Utqiaġvik, Alaska
Authors: Qiu Shaoyue , Xi Baike , Dong Xiquan
Published: August 2018

Seven years of autumnal ground‐based observations (September–November 2002–2008) at the U.S. Department of Energy Atmospheric Radiation Measurement North Slope of Alaska site have been analyzed for addressing the occurrence frequency and macrophysical and microphysical properties of Arctic mixed‐phase clouds (AMC), as well as the relationship between environmental parameters and AMC properties. In September and October, AMC occurrence frequency is 20–30% lower during a southerly wind when compared to the other wind directions; in November, the variation of AMC occurrence frequency with wind direction is small. The mean liquid water path in November is about half of that in October and September. When the surface is snow free, temperature (T) and specific humidity (q) profiles during a northerly wind are warmer and moister than those for the southerly wind. Northerly wind profiles have a higher relative humidity to ice (RHi) and lower atmosphere stability. Furthermore, the AMC occurrence frequency has a positive relationship with RHi and a negative relationship with stability. These two points may explain the lower AMC occurrence frequency during a southerly wind. During a northerly wind, AMCs have larger radar reflectivity, wider spectrum width, and larger Doppler velocity signatures. The stronger precipitation for AMC during a northerly wind is possibly due to the cleaner air masses from the ocean (north). With the same amount of q, the radar spectrum width has a higher frequency in the larger bins during a northerly wind. Both T, q, and radar reflectivity, radar spectrum width profiles show evidence of deposition in the sub‐cloud layer in September and October.
Impact of Ice Surface and Volume Scatterings on the Microwave Sea Ice Apparent Emissivity
Authors: Lee Sang‐Moo , Sohn Byung‐Ju , Shi Hoyeon
Published: August 2018

Emissivity retrieval for sea ice from passive microwave measurements has been an important problem in climate/environmental research because of its link to various snow/ice variables. However, so far, it has been a difficult task because of the influences of surface and snow/ice induced volume scatterings. Here we examine the influences of scatterings on the ice emissivity from 10.65, 18.7, 23.8, and 36.5 GHz Advanced Microwave Scanning Radiometer (AMSR)‐E brightness temperatures over the Arctic Ocean. In doing so, we use a two‐dimensional roughness parameterization, modified with surface facet orientations with an assumption that the facet emission follows the Fresnel relationship. Emitting layer temperature and refractive index retrieved from AMSR‐E 6.9 GHz brightness temperature measurements were used in this study and applied to other channels of interest. We demonstrated that the obtained roughness index has a strong linear relationship with the root‐mean‐square height measured by Atmospheric Terrain Mapper on the National Aeronautics and Space Administration (NASA) P‐3 aircraft. The obtained roughness index showed that surface scattering on the emissivity is generally insignificant except for some first‐year ice regions in particular at higher frequencies. This fact implies that Fresnel relations can be applicable for most of sea ice at the low‐frequency microwave spectrum. By contrast, volume scattering is found to be significant in emissivity retrieval in case of multiyear ice. Nonetheless, volume scattering influence over first‐year ice appears to be minor. We suggest that Fresnel‐type emissivity can be estimated once a correction factor is used for removing surface scattering and volume scattering contributions from the apparent emissivity.
Geological Features and Evolution of Yardangs in the Qaidam Basin, Tibetan Plateau (NW China): A Terrestrial Analogue for Mars
Authors: Wang Jiang , Xiao Long , Reiss Dennis , Hiesinger Harald , Huang Jun , Xu Yi , Zhao Jiannan , Xiao Zhiyong , Komatsu Goro
Published: August 2018

Wind‐eroded ridges known as yardangs are common in most arid desert regions on Earth, as well as on other planets, notably in the Medusae Fossae Formation (MFF) and Gale Crater on Mars. However, the formation and evolution of these various yardangs are not well understood, which, therefore, requires further studies by more terrestrial analogues. Here we report a detailed investigation of the terrestrial yardang fields in the Qaidam Basin, northeastern Tibetan Plateau, China. Most of them are distributed in the northwestern and central eastern parts, with dominant orientations northwest to north‐northeast and approximately west to east, respectively. Based on their morphologies and distributions, yardangs within the Qaidam Basin have been classified into 11 different types out of four main groups. Wind is the dominant driver of yardang erosion, but water, salt, and mass wasting may also have played important roles in their formation and modification. A four‐step evolution model, including embryonic, adolescent, mature, and receding stages, is proposed to reveal their formation and evolution in the basin. Meanwhile, yardangs in the MFF and Gale Crater on Mars have morphologic and geometric characteristics that show striking similarities to those in the Qaidam Basin. The fact that some yardang fields in MFF on Mars also show overlapping relationships suggests that they possibly have experienced a multistage evolution, during which the evolution processes may have been interrupted at some stages due to differences in the competence of rocks and/or the changes of the environment.
Phosphorus Fractionation Responds to Dynamic Redox Conditions in a Humid Tropical Forest Soil
Authors: Lin Yang , Bhattacharyya Amrita , Campbell Ashley N. , Nico Peter S. , Pett‐Ridge Jennifer , Silver Whendee L.
Published: August 2018

Phosphorus (P) is a key limiting nutrient in highly weathered soils of humid tropical forests. A large proportion of P in these soils is bound to redox‐sensitive iron (Fe) minerals; however, little is known about how Fe redox interactions affect soil P cycling. In an incubation experiment, we changed bulk soil redox regimes by varying headspace conditions (air versus N2 gas) and examined the responses of soil P and Fe species to two fluctuating treatments (4‐ or 8‐day oxic followed by 4‐day anoxic) and two static redox treatments (oxic and anoxic). A static anoxic headspace increased NaOH‐extractable inorganic P and ammonium oxalate‐extractable total P (AO‐Pt) by 10% and 38%, respectively, relative to a static oxic headspace. Persistent anoxia also increased NaHCO3‐extractable total P (NaHCO3‐Pt) toward the end of the experiment. Effects of redox fluctuation were more complex and dependent on temporal scales. Ammonium oxalate‐extractable Fe and Pt concentrations responded to redox fluctuation early in the experiment, but not thereafter, suggesting a depletion of reductant over time. Immediately following a switch from an oxic to anoxic headspace, concentrations of AO‐Pt, AO‐Fe, and HCl‐extractable Fe(II) increased (within 30 min) but fell back to initial levels by 180 min. Surprisingly, the labile P pool (NaHCO3‐Pt) decreased immediately after reduction events, potentially due to resorption and microbial uptake. Overall, our data demonstrate that P fractions can respond rapidly to changes in soil redox conditions, and in environments where redox oscillation is common, roots and microbes may benefit from these rapid P dynamics.
Assessment of the Simulation of Gravity Waves Generation by a Tropical Cyclone in the High‐Resolution WACCM and the WRF
Authors: Wu J. F. , Xue X. H. , Liu H. L. , Dou X. K. , Chen T. D.
Published: August 2018

National Center for Atmospheric Research Whole Atmosphere Community Climate Model (WACCM) with quasi‐uniform grid of ∼25‐km horizontal resolution can resolve gravity waves (GWs) with horizontal scales down to ∼250 km. In this study, the scale interactions between the GWs resolved by WACCM and those with smaller scales, its potential impact on the resolved waves, and the dependence of wave characteristics on spatial resolution are examined. The Weather Research and Forecasting (WRF) simulations with five different spatial resolutions (25, 20, 15, 10, and 4 km) are performed, with the high‐resolution WACCM wind and temperature fields as initial and boundary conditions. Semicircular GWs excited by a tropical cyclone (TC) resolved by WACCM and WRF (25‐km resolution) are found at similar locations and have similar structures. In this study, the sensitivity of GW structure to the choice of model horizontal resolutions is examined. Although WRF is successful in generating semicircular GWs in each case, the simulation reveals more power at shorter horizontal wavelengths of GWs at finer resolutions. Furthermore, we evaluate the performance of all these simulations in resolving GWs induced by the tropical cyclone (TGWs). The magnitude of the zonal momentum flux calculated from the high‐resolution WACCM is greater than the WRF‐25 simulation, in addition, the magnitude is comparable to the results from the WRF‐15 and WRF‐10 simulations.
Future prospects of immune checkpoint blockade in cancer: from response prediction to overcoming resistance
Authors: Park Young-Jun , Kuen Da-Sol , Chung Yeonseok
Published: August 2018

Recent advances in the understating of tumor immunology suggest that cancer immunotherapy is an effective treatment against various types of cancer. In particular, the remarkable successes of immune checkpoint-blocking antibodies in clinical settings have encouraged researchers to focus on developing other various immunologic strategies to combat cancer. However, such immunotherapies still face difficulties in controlling malignancy in many patients due to the heterogeneity of both tumors and individual patients. Here, we discuss how tumor-intrinsic cues, tumor environmental metabolites, and host-derived immune cells might impact the efficacy and resistance often seen during immune checkpoint blockade treatment. Furthermore, we introduce biomarkers identified from human and mouse models that predict clinical benefits for immune checkpoint blockers in cancer.
Fatostatin induces pro- and anti-apoptotic lipid accumulation in breast cancer
Authors: Brovkovych Viktor , Izhar Yasir , Danes Jeanne M. , Dubrovskyi Oleskii , Sakallioglu Isin T. , Morrow Lauren M. , Atilla-Gokcumen G. Ekin , Frasor Jonna
Published: August 2018

Given the dependence of cancers on de novo lipogenesis, we tested the effect of fatostatin, a small molecule thought to target this pathway by blocking activation of SREBP transcription factors, in breast cancer cell lines and xenograft tumors. We found that estrogen receptor (ER) positive cells were more sensitive to fatostatin than ER negative cells and responded with cell cycle arrest and apoptosis. Surprisingly, we found that rather than inhibiting lipogenesis, fatostatin caused an accumulation of lipids as a response to endoplasmic reticulum stress rather than inhibition of SREBP activity. In particular, ceramide and dihydroceramide levels increased and contributed to the apoptotic effects of fatostatin. In addition, an accumulation of triacylglycerides (TAGs), particularly those containing polyunsaturated fatty acids (PUFAs), was also observed as a result of elevated diacylglycerol transferase activity. Blocking PUFA-TAG production enhanced the apoptotic effect of fatostatin, suggesting that these lipids play a protective role and limit fatostatin response. Together, these findings indicate that the ability of breast cancer cells to respond to fatostatin depends on induction of endoplasmic reticulum stress and subsequent ceramide accumulation, and that limiting production of PUFA-TAGs may be therapeutically beneficial in specific tumor subtypes.
Seasonality of the gut microbiota of free-ranging white-faced capuchins in a tropical dry forest
Authors: Orkin Joseph D , Campos Fernando A , Myers Monica S , Cheves Hernandez Saul E , Guadamuz Adrián , Melin Amanda D
Published: August 2018

Research on the gut microbiota of free-ranging mammals is offering new insights into dietary ecology. However, for free-ranging primates, little information is available for how microbiomes are influenced by ecological variation through time. Primates inhabiting seasonal tropical dry forests undergo seasonally specific decreases in food abundance and water availability, which have been linked to adverse health effects. Throughout the course of a seasonal transition in 2014, we collected fecal samples from three social groups of free-ranging white-faced capuchin monkeys (Cebus capucinus imitator) in Sector Santa Rosa, Área de Conservación Guanacaste, Costa Rica. 16S rRNA sequencing data reveal that unlike other primates, the white-faced capuchin monkey gut is dominated by Bifidobacterium and Streptococcus. Linear mixed effects models indicate that abundances of these genera are associated with fluctuating availability and consumption of fruit and arthropods, whereas beta diversity clusters by rainfall season. Whole shotgun metagenomics revealed that the capuchin gut is dominated by carbohydrate-binding modules associated with digestion of plant polysaccharides and chitin, matching seasonal dietary patterns. We conclude that rainfall and diet are associated with the diversity, composition, and function of the capuchin gut microbiome. Additionally, microbial fluctuations are likely contributing to nutrient uptake and the health of wild primate populations.
Cell-type-specific interrogation of CeA Drd2 neurons to identify targets for pharmacological modulation of fear extinction
Authors: McCullough Kenneth M. , Daskalakis Nikolaos P. , Gafford Georgette , Morrison Filomene G. , Ressler Kerry J.
Published: August 2018

Behavioral and molecular characterization of cell-type-specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders. Examining cell-type-specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning, mirroring possible treatment strategies in humans. Here we identify the central amygdala (CeA) Drd2-expressing population as a novel fear-supporting neuronal population that is molecularly distinct from other, previously identified, fear-supporting CeA populations. Sequencing of actively translating transcripts of Drd2 neurons using translating ribosome affinity purification (TRAP) technology identifies mRNAs that are differentially regulated following fear learning. Differentially expressed transcripts with potentially targetable gene products include Npy5r, Rxrg, Adora2a, Sst5r, Fgf3, Erbb4, Fkbp14, Dlk1, and Ssh3. Direct pharmacological manipulation of NPY5R, RXR, and ADORA2A confirms the importance of this cell population and these cell-type-specific receptors in fear behavior. Furthermore, these findings validate the use of functionally identified specific cell populations to predict novel pharmacological targets for the modulation of emotional learning.
Sensorineural hearing loss and mild cardiac phenotype caused by an EYA4 mutation
Authors: Abe Satoko , Takeda Hidehiko , Nishio Shin-ya , Usami Shin-ichi
Published: August 2018

EYA4 is a member of the vertebrate eya gene family of transcriptional activators and plays several roles in both embryonic and inner ear development. The majority of EYA4 gene mutations are associated with autosomal dominant non-syndromic hearing loss (DFNA10). In addition, some mutations in this gene cause autosomal dominant syndromic hearing loss with dilated cardiomyopathy. EYA4 is a rare cause of sensorineural hearing loss, and only a limited number of papers regarding mutations in this gene have been published. Thus, detailed clinical features remain unclear.

We conducted next-generation sequencing of a Japanese individual with progressive sensorineural hearing loss and identified an EYA4 pathogenic variant. Pure-tone audiometry revealed bilateral, nearly symmetric, moderate sensorineural hearing loss in the low and middle frequencies. Minor abnormalities were observed on the patient’s electrocardiogram and echocardiography without any apparent symptoms. Next-generation sequencing is effective in elucidating the etiology of hearing loss, and the present findings suggested the possible phenotypic expansion of deafness caused by EYA4 gene mutations.
Phosphorylation of ULK1 affects autophagosome fusion and links chaperone-mediated autophagy to macroautophagy
Authors: Wang Chenyao , Wang Huafei , Zhang Deyi , Luo Wenwen , Liu Ruilong , Xu Daqian , Diao Lei , Liao Lujian , Liu Zhixue
Published: August 2018

The Unc-51 like autophagy activating kinase 1 (ULK1) complex plays a central role in the initiation stage of autophagy. However, the function of ULK1 in the late stage of autophagy is unknown. Here, we report that ULK1, a central kinase of the ULK1 complex involved in autophagy initiation, promotes autophagosome–lysosome fusion. PKCα phosphorylates ULK1 and prevents autolysosome formation. PKCα phosphorylation of ULK1 does not change its kinase activity; however, it decreases autophagosome–lysosome fusion by reducing the affinity of ULK1 for syntaxin 17 (STX17). Unphosphorylated ULK1 recruited STX17 and increased STX17′s affinity towards synaptosomal-associated protein 29 (SNAP29). Additionally, phosphorylation of ULK1 enhances its interaction with heat shock cognate 70 kDa protein (HSC70) and increases its degradation through chaperone-mediated autophagy (CMA). Our study unearths a key mechanism underlying autolysosome formation, a process in which the kinase activity of PKCα plays an instrumental role, and reveals the significance of the mutual regulation of macroautophagy and CMA in maintaining the balance of autophagy.
Evaluating intrinsic and non-intrinsic cancer risk factors
Authors: Wu Song , Zhu Wei , Thompson Patricia , Hannun Yusuf A
Published: August 2018

Discriminating the contribution of unmodifiable random intrinsic DNA replication errors (‘bad luck’) to cancer development from those of other factors is critical for understanding cancer in humans and for directing public resources aimed at reducing the burden of cancer. Here, we review and highlight the evidence that demonstrates cancer causation is multifactorial, and provide several important examples where modification of risk factors has achieved cancer prevention. Furthermore, we stress the need and opportunities to advance understanding of cancer aetiology through integration of interaction effects between risk factors when estimating the contribution of individual and joint factors to cancer burden in a population. We posit that non-intrinsic factors drive most cancer risk, and stress the need for cancer prevention.
March1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity
Authors: Borges Thiago J. , Murakami Naoka , Machado Felipe D. , Murshid Ayesha , Lang Benjamin J. , Lopes Rafael L. , Bellan Laura M. , Uehara Mayuko , Antunes Krist H. , Pérez-Saéz Maria José , Birrane Gabriel , Vianna Priscila , Gonçalves João Ismael B. , Zanin Rafael F. , Azzi Jamil , Abdi Reza , Ishido Satoshi , Shin Jeoung-Sook , Souza Ana Paula D. , Calderwood Stuart K. , Riella Leonardo V. , Bonorino Cristina
Published: August 2018

In transplantation, donor dendritic cells (do-DCs) initiate the alloimmune response either by direct interaction with host T cells or by transferring intact donor MHC to host DCs. However, how do-DCs can be targeted for improving allograft survival is still unclear. Here we show CD103+ DCs are the major do-DC subset involved in the acute rejection of murine skin transplants. In the absence of CD103+ do-DCs, less donor MHC-II is carried to host lymph nodes, fewer allogenic T cells are primed and allograft survival is prolonged. Incubation of skin grafts with the anti-inflammatory mycobacterial protein DnaK reduces donor MHC-II on CD103+DCs and prolongs graft survival. This effect is mediated through IL-10-induced March1, which ubiquitinates and decreases MHC-II levels. Importantly, in vitro pre-treatment of human DCs with DnaK reduces their ability to prime alloreactive T cells. Our findings demonstrate a novel therapeutic approach to dampen alloimmunity by targeting donor MHC-II on CD103+DCs.
Modelling of free-form conformal metasurfaces
Authors: Wu Kedi , Coquet Philippe , Wang Qi Jie , Genevet Patrice
Published: August 2018

Artificial electromagnetic surfaces, metasurfaces, control light in the desired manner through the introduction of abrupt changes of electromagnetic fields at interfaces. Current modelling of metasurfaces successfully exploits generalised sheet transition conditions (GSTCs), a set of boundary conditions that account for electric and magnetic metasurface-induced optical responses. GSTCs are powerful theoretical tools but they are not readily applicable for arbitrarily shaped metasurfaces. Accurate and computationally efficient algorithms capable of implementing artificial boundary conditions are highly desired for designing free-form photonic devices. To address this challenge, we propose a numerical method based on conformal boundary optics with a modified finite difference time-domain (FDTD) approach which accurately calculates the electromagnetic fields across conformal metasurfaces. Illustrative examples of curved meta-optics are presented, showing results in good agreement with theoretical predictions. This method can become a powerful tool for designing and predicting optical functionalities of conformal metasurfaces for new lightweight, flexible and wearable photonic devices.
High-performance artificial nitrogen fixation at ambient conditions using a metal-free electrocatalyst
Authors: Qiu Weibin , Xie Xiao-Ying , Qiu Jianding , Fang Wei-Hai , Liang Ruping , Ren Xiang , Ji Xuqiang , Cui Guanwei , Asiri Abdullah M. , Cui Ganglong , Tang Bo , Sun Xuping
Published: August 2018

Conversion of naturally abundant nitrogen to ammonia is a key (bio)chemical process to sustain life and represents a major challenge in chemistry and biology. Electrochemical reduction is emerging as a sustainable strategy for artificial nitrogen fixation at ambient conditions by tackling the hydrogen- and energy-intensive operations of the Haber–Bosch process. However, it is severely challenged by nitrogen activation and requires efficient catalysts for the nitrogen reduction reaction. Here we report that a boron carbide nanosheet acts as a metal-free catalyst for high-performance electrochemical nitrogen-to-ammonia fixation at ambient conditions. The catalyst can achieve a high ammonia yield of 26.57 μg h–1 mg–1cat. and a fairly high Faradaic efficiency of 15.95% at –0.75 V versus reversible hydrogen electrode, placing it among the most active aqueous-based nitrogen reduction reaction electrocatalysts. Notably, it also shows high electrochemical stability and excellent selectivity. The catalytic mechanism is assessed using density functional theory calculations.
The prognostic effects of somatic mutations in ER-positive breast cancer
Authors: Griffith Obi L. , Spies Nicholas C. , Anurag Meenakshi , Griffith Malachi , Luo Jingqin , Tu Dongsheng , Yeo Belinda , Kunisaki Jason , Miller Christopher A , Krysiak Kilannin , Hundal Jasreet , Ainscough Benjamin J , Skidmore Zachary L. , Campbell Katie , Kumar Runjun , Fronick Catrina , Cook Lisa , Snider Jacqueline E. , Davies Sherri , Kavuri Shyam M. , Chang Eric C. , Magrini Vincent , Larson David E. , Fulton Robert S , Liu Shuzhen , Leung Samuel , Voduc David , Bose Ron , Dowsett Mitch , Wilson Richard K. , Nielsen Torsten O. , Mardis Elaine R , Ellis Matthew J.
Published: August 2018

Here we report targeted sequencing of 83 genes using DNA from primary breast cancer samples from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients to determine interactions between somatic mutation and prognosis. Independent validation of prognostic interactions was achieved using data from the METABRIC study. Previously established associations between MAP3K1 and PIK3CA mutations with luminal A status/favorable prognosis and TP53 mutations with Luminal B/non-luminal tumors/poor prognosis were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutations were also a poor outcome driver that was validated in METABRIC. For MA12, poor outcome associated with PIK3R1 mutation was also reproducible. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false discovery correction (q = 0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typifies ER+ breast cancer.
Structural homogeneity and mass density of bulk metallic glasses revealed by their rough surfaces and ultra-small angle neutron scattering (USANS)
Authors: Kim Man-Ho , Suh Jin-Yoo , Fleury Eric , Han Su Gyeong , Hong Kyung Tae
Published: August 2018

The ultra-small angle neutron scattering (USANS) measures the microscale structure of heterogeneity and the scattering from rough surfaces with small scattering volumes can be neglected. But this is not true in amorphous alloys. The small angle scattering from such surfaces is not negligible, regardless of scattering volume. However, we demonstrate that the unwanted rough surfaces can be utilized to determine the homogeneity and mass density of amorphous metallic glasses using the USANS and surface neutron contrast matching technique. The power law scattering of the homogeneous Cu50Zr50 amorphous alloy disappeared under the surface contrast-matched environment, a mixture of hydrogenated/deuterated ethanol having low surface tension against the metallic alloys, indicating that the scattering originated not from its internal structure but from the rough surface. This confirms the structural homogeneity not only at the atomic level but also on a larger scale of micrometer. On the other hand, the crystallized Cu50Zr50 alloy showed strong power-law scattering under the matching environment due to the structural heterogeneity inside the alloy. This technique can apply to the bulk samples when the transmission is high enough not causing multiple scattering that is easily detected with USANS and when the surface roughness is dominant source of scattering.
The 2015 landslide and tsunami in Taan Fiord, Alaska
Authors: Higman Bretwood , Shugar Dan H. , Stark Colin P. , Ekström Göran , Koppes Michele N. , Lynett Patrick , Dufresne Anja , Haeussler Peter J. , Geertsema Marten , Gulick Sean , Mattox Andrew , Venditti Jeremy G. , Walton Maureen A. L. , McCall Naoma , Mckittrick Erin , MacInnes Breanyn , Bilderback Eric L. , Tang Hui , Willis Michael J. , Richmond Bruce , Reece Robert S. , Larsen Chris , Olson Bjorn , Capra James , Ayca Aykut , Bloom Colin , Williams Haley , Bonno Doug , Weiss Robert , Keen Adam , Skanavis Vassilios , Loso Michael
Published: August 2018

Glacial retreat in recent decades has exposed unstable slopes and allowed deep water to extend beneath some of those slopes. Slope failure at the terminus of Tyndall Glacier on 17 October 2015 sent 180 million tons of rock into Taan Fiord, Alaska. The resulting tsunami reached elevations as high as 193 m, one of the highest tsunami runups ever documented worldwide. Precursory deformation began decades before failure, and the event left a distinct sedimentary record, showing that geologic evidence can help understand past occurrences of similar events, and might provide forewarning. The event was detected within hours through automated seismological techniques, which also estimated the mass and direction of the slide - all of which were later confirmed by remote sensing. Our field observations provide a benchmark for modeling landslide and tsunami hazards. Inverse and forward modeling can provide the framework of a detailed understanding of the geologic and hazards implications of similar events. Our results call attention to an indirect effect of climate change that is increasing the frequency and magnitude of natural hazards near glaciated mountains.
Unaltered intrinsic functional brain architecture in young women with primary dysmenorrhea
Authors: Lee Lin-Chien , Chen Yueh-Hua , Lin Chia-Shu , Li Wei-Chi , Low Intan , Tu Cheng-Hao , Chou Chih-Che , Cheng Chou-Ming , Yeh Tzu-Chen , Chen Li-Fen , Chao Hsiang-Tai , Hsieh Jen-Chuen
Published: August 2018

Primary dysmenorrhea (PDM), painful menstruation without organic causes, is the most prevalent gynecological problem in women of reproductive age. Dysmenorrhea later in life often co-occurs with many chronic functional pain disorders, and chronic functional pain disorders exhibit altered large-scale connectedness between distributed brain regions. It is unknown whether the young PDM females exhibit alterations in the global and local connectivity properties of brain functional networks. Fifty-seven otherwise healthy young PDM females and 62 age- and education-matched control females participated in the present resting-state functional magnetic resonance imaging study. We used graph theoretical network analysis to investigate the global and regional network metrics and modular structure of the resting-state brain functional networks in young PDM females. The functional network was constructed by the interregional functional connectivity among parcellated brain regions. The global and regional network metrics and modular structure of the resting-state brain functional networks were not altered in young PDM females at our detection threshold (medium to large effect size differences [Cohen’s d ≥ 0.52]). It is plausible that the absence of significant changes in the intrinsic functional brain architecture allows young PDM females to maintain normal psychosocial outcomes during the pain-free follicular phase.
Self-report data as a tool for subtype identification in genetically-defined Parkinson’s Disease
Authors: Winslow Ashley R. , Hyde Craig L. , Wilk Jemma B. , Eriksson Nicholas , Cannon Paul , Miller Melissa R. , Hirst Warren D.
Published: August 2018

Through a targeted recruitment 23andMe has collected DNA and patient-reported symptoms from more than 10,000 subjects reporting a physician-verified diagnosis of PD. This study evaluated the potential of self-report, web-based questionnaires to rapidly assess disease natural history and symptomology in genetically-defined PD populations. While average age-at-diagnosis was significantly lower in GBA mutation carriers compared to idiopathic PD, or iPD (idiopathic PD, defined as no GBA mutations and no LRRK2 G2019S mutation), there were no significant differences in symptoms. Conversely, LRRK2 G2019S carrier status significantly associated with reporting of milder daily symptoms of lightheadedness and several differences were observed at a false discovery rate < 0.1, including increased reporting of changes in walking as an initial symptom of disease, decreased reporting of lightheadedness upon standing, and milder symptoms related to daily functioning. The subclinical differences in symptoms reported by LRRK2 G2019S carriers suggest differences in underlying pathophysiology and/or disease progression in LRRK2 carriers compared to iPD. Importantly, we confirm previous findings in PD genetic subsets where disease characteristics were ascertained through clinical exam. Overall, these data support the effective use of self-report and genetic data to rapidly analyze information from a large disease population or difficult to identify genetic subgroups.
Acoustic Tweezing Cytometry Induces Rapid Initiation of Human Embryonic Stem Cell Differentiation
Authors: Topal Tuğba , Hong Xiaowei , Xue Xufeng , Fan Zhenzhen , Kanetkar Ninad , Nguyen Joe T. , Fu Jianping , Deng Cheri X. , Krebsbach Paul H.
Published: August 2018

Mechanical forces play critical roles in influencing human embryonic stem cell (hESC) fate. However, it remains largely uncharacterized how local mechanical forces influence hESC behavior in vitro. Here, we used an ultrasound (US) technique, acoustic tweezing cytometry (ATC), to apply targeted cyclic subcellular forces to hESCs via integrin-bound microbubbles (MBs). We found that ATC-mediated cyclic forces applied for 30 min to hESCs near the edge of a colony induced immediate global responses throughout the colony, suggesting the importance of cell-cell connection in the mechanoresponsiveness of hESCs to ATC-applied forces. ATC application generated increased contractile force, enhanced calcium activity, as well as decreased expression of pluripotency transcription factors Oct4 and Nanog, leading to rapid initiation of hESC differentiation and characteristic epithelial-mesenchymal transition (EMT) events that depend on focal adhesion kinase (FAK) activation and cytoskeleton (CSK) tension. These results reveal a unique, rapid mechanoresponsiveness and community behavior of hESCs to integrin-targeted cyclic forces.
Outer membrane lipoprotein RlpA is a novel periplasmic interaction partner of the cell division protein FtsK in Escherichia coli
Authors: Berezuk Alison M. , Glavota Sabrina , Roach Elyse J. , Goodyear Mara C. , Krieger Jonathan R. , Khursigara Cezar M.
Published: August 2018

In Escherichia coli, formation of new cells is mediated by the elongasome and divisome that govern cell elongation and septation, respectively. Proper transition between these events is essential to ensure viable progeny are produced; however, the components of each complex responsible for transmission of the cell signal to shift from elongation to septation are unclear. Recently, a region within the N-terminal domain of the essential divisome protein FtsK (FtsKN) was identified that points to a key role for FtsK as a checkpoint of cell envelope remodeling during division. Here, we used site-specific in vivo UV cross-linking to probe the periplasmic loops of FtsKN for protein interaction partners critical for FtsKN function. Mass spectrometry analysis of five unique FtsKN periplasmic cross-links revealed a network of potential FtsKN interactors, one of which included the septal peptidoglycan binding protein rare lipoprotein A (RlpA). This protein was further verified as a novel interaction partner of FtsKN by an in vitro pull-down assay. Deletion of rlpA from an FtsK temperature-sensitive E. coli strain partially restored cell growth and largely suppressed cellular filamentation compared to the wild-type strain. This suggests that interaction with RlpA may be critical in suppressing septation until proper assembly of the divisome.
Histo-blood group antigen-binding specificities of human rotaviruses are associated with gastroenteritis but not with in vitro infection
Authors: Barbé Laure , Le Moullac-Vaidye Béatrice , Echasserieau Klara , Bernardeau Karine , Carton Thomas , Bovin Nicolai , Nordgren Johan , Svensson Lennart , Ruvoën-Clouet Nathalie , Le Pendu Jacques
Published: August 2018

Human strains of rotavirus A (RVAs) recognize fucosylated glycans belonging to histo-blood group antigens (HBGAs) through their spike protein VP8*. Lack of these ligands due to genetic polymorphisms is associated with resistance to gastroenteritis caused by P[8] genotype RVAs. With the aim to delineate the contribution of HBGAs in the process, we analyzed the glycan specificity of VP8* proteins from various P genotypes. Binding to saliva of VP8* from P[8] and P[4] genotypes required expression of both FUT2 and FUT3 enzymes, whilst binding of VP8* from the P[14] genotype required FUT2 and A enzymes. We further defined a glycan motif, GlcNAcβ3Galβ4GlcNAc, recognized by P[6] clinical strains. Conversion into Lewis antigens by the FUT3 enzyme impaired recognition, explaining their lower binding to saliva of Lewis positive phenotype. In addition, the presence of neutralizing antibodies was associated with the presence of theFUT2wild type allele in sera from young healthy adults. Nonetheless,in vitroinfection of transformed cell lines was independent of HBGAs expression, indicating that HBGAs are not human RV receptors. The match between results from saliva-based binding assays and the epidemiological data indicates that the polymorphism of human HBGAs controls susceptibility to RVAs, although the exact mechanism remains unclear.
Sonication of heart valves detects more bacteria in infective endocarditis
Authors: Gomes Anna , van Oosten Marleen , Bijker Kasper L. B. , Boiten Kathleen E. , Salomon Elisa N. , Rosema Sigrid , Rossen John W. A. , Natour Ehsan , Douglas Yvonne L. , Kampinga Greetje A. , van Assen Sander , Sinha Bhanu
Published: August 2018

Optimal antimicrobial treatment of infective endocarditis requires identification and susceptibility patterns of pathogens. Sonication of explanted heart valves could increase the identification and culture of pathogens, as shown in prosthetic joint and pacemaker/ICD infections. We tested 26 explanted heart valves from 20 patients with active definite endocarditis for added diagnostic value of sonication to the standard microbiological workup in a prospective diagnostic proof of concept study. Two sonication protocols (broth enrichment vs. centrifugation) were compared in an additional 35 negative control valves for contamination rates. We selected sonication/centrifugation based on acceptable false positive rates (11.4%; 4/35). Sonication/enrichment yielded many false positive results in negative controls (28.6%; 10/35), mainly Propionibacterium acnes (next-generation sequencing excluded technical problems). Compared to direct culture only, adding sonication/centrifugation (including molecular testing) significantly increased the diagnostic yield from 6/26 to 17/26 valves (p = 0.003). Most importantly, culture positives almost doubled (from 6 to 10), providing unique quantitative information about antimicrobial susceptibility. Even if direct molecular testing was added to the standard workup, sonication/centrifugation provided additional diagnostic information in a significant number of valves (8/26; 31%; p = 0.013). We concluded that sonication/centrifugation added relevant diagnostic information in the workup of heart valves with infective endocarditis, with acceptable contamination rates.
Scenario analysis of ecosystem service changes and interactions in a mountain-oasis-desert system: a case study in Altay Prefecture, China
Authors: Fu Qi , Hou Ying , Wang Bo , Bi Xu , Li Bo , Zhang Xinshi
Published: August 2018

Scenario analysis of ecosystem services (ES) can provide a scientific basis for ecosystem management. The objective of this study was to reveal the effects of future land use scenarios on ES in a mountain-oasis-desert system (MODS). We first simulated land use changes for the period of 2015–2035 in Altay Prefecture under three different scenarios: business as usual (BAU), economic development (ED), and ecological conservation (EC). We then evaluated water yield (WY), crop production (CP), soil conservation (SC), sand fixation (SF), carbon sequestration (CS), and aesthetic value (AV) and investigated the multiple interactions among ES at the regional and grid scales. The results showed that SC, CS, and AV continually increased, WY continually decreased under the three scenarios. Our study revealed that the multiple interactions among ES were spatially heterogeneous in the MODS and the spatial heterogeneities changed across scenarios. The locations of and causes for the formation of the multiple interactions among ES were identified based on spatial analysis. This information can help decision-makers develop targeted and differentiated ecosystem management strategies. This study can increase the understanding of the multiple interactions among ES. Our findings can provide a reference for studies of other regions with the MODS structure.
Evaluation of modified Interferon alpha mRNA constructs for the treatment of non-melanoma skin cancer
Authors: Hochmann Sarah , Mittermeir Michaela , Santic Radmila , Koszik Frieder , Griessner Lanay , Sonderegger Alina Sarah , Hoffmann Thomas , Russe Elisabeth , Scheiblhofer Sandra , Weiss Richard , Mandler Markus , Schneeberger Achim , Strunk Dirk
Published: August 2018

Application of in vitro transcribed (IVT) messenger ribonucleic acid (mRNA) is an increasingly popular strategy to transiently produce proteins as therapeutics in a tissue or organ of choice. Here, we focused on the skin and aimed to test if whole human skin tissue explant technology can be used to evaluate the expression efficacy of different IVT Interferon alpha (IFN-α) mRNA constructs in situ, after biolistic delivery. Skin explants were viable and intact for at least five days based on histologic analysis and TUNEL staining. Using GFP reporter mRNA formulations, we found mostly epidermal expression after biolistic delivery. Two out of five sequence-optimized IFN-α mRNA variants resulted in significantly improved IFN-α protein expression in human skin compared to native IFN-α mRNA transfection. IFN-α secretion analysis of the surrounding culture media confirmed these results. We provide a proof-of-concept that IFN-α mRNA delivery into intact human full thickness skin explants can be utilized to test mRNA sequence modifications ex vivo. This approach could be used to develop novel mRNA-based treatments of common epidermal skin conditions including non-melanoma skin cancer, where IFN-α protein therapy has previously shown a strong therapeutic effect.