bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of HIV‐1 reverse transcriptase/d4TTP complex: Novel DNA cross‐linking site and pH‐dependent conformational changes
Authors: Martinez Sergio E. , Bauman Joseph D. , Das Kalyan , Arnold Eddy
Published: November 2018

Stavudine (d4T, 2′,3′‐didehydro‐2′,3′‐dideoxythymidine) was one of the first chain‐terminating nucleoside analogs used to treat HIV infection. We present the first structure of the active, triphosphate form of d4T (d4TTP) bound to a catalytic complex of HIV‐1 RT/dsDNA template‐primer. We also present a new strategy for disulfide (S–S) chemical cross‐linking between N6 of a modified adenine at the second overhang base to I63C in the fingers subdomain of RT. The cross‐link site is upstream of the duplex‐binding region of RT, however, the structure is very similar to published RT structures with cross‐linking to Q258C in the thumb, which suggests that cross‐linking at either site does not appreciably perturb the RT/DNA structures. RT has a catalytic maximum at pH 7.5. We determined the X‐ray structures of the I63C‐RT/dsDNA/d4TTP cross‐linked complexes at pH 7, 7.5, 8, 8.5, 9, and 9.5. We found small (~0.5 Å), pH‐dependent motions of the fingers subdomain that folds in to form the dNTP‐binding pocket. We propose that the pH‐activity profile of RT relates to this motion of the fingers. Due to side effects of neuropathy and lipodystrophy, use of d4T has been stopped in most countries, however, chemical modification of d4T might lead to the development of a new class of nucleoside analogs targeting RNA and DNA polymerases.
Quantitative collision‐induced unfolding differentiates model antibody–drug conjugates
Authors: Tian Yuwei , Lippens Jennifer L. , Netirojjanakul Chawita , Campuzano Iain D.G. , Ruotolo Brandon T.
Published: November 2018

Antibody–drug conjugates (ADCs) are antibody‐based therapeutics that have proven to be highly effective cancer treatment platforms. They are composed of monoclonal antibodies conjugated with highly potent drugs via chemical linkers. Compared to cysteine‐targeted chemistries, conjugation at native lysine residues can lead to a higher degree of structural heterogeneity, and thus it is important to evaluate the impact of conjugation on antibody conformation. Here, we present a workflow involving native ion mobility (IM)‐MS and gas‐phase unfolding for the structural characterization of lysine‐linked monoclonal antibody (mAb)–biotin conjugates. Following the determination of conjugation states via denaturing Liquid Chromatography‐Mass Spectrometry (LC–MS) measurements, we performed both size exclusion chromatography (SEC) and native IM‐MS measurements in order to compare the structures of biotinylated and unmodified IgG1 molecules. Hydrodynamic radii (Rh) and collision cross‐sectional (CCS) values were insufficient to distinguish the conformational changes in these antibody–biotin conjugates owing to their flexible structures and limited instrument resolution. In contrast, collision induced unfolding (CIU) analyses were able to detect subtle structural and stability differences in the mAb upon biotin conjugation, exhibiting a sensitivity to mAb conjugation that exceeds native MS analysis alone. Destabilization of mAb–biotin conjugates was detected by both CIU and differential scanning calorimetry (DSC) data, suggesting a previously unknown correlation between the two measurement tools. We conclude by discussing the impact of IM‐MS and CIU technologies on the future of ADC development pipelines.
A 17‐year‐old woman with a solitary, mixed squamous cell and glandular papilloma of the bronchus
Authors: Saraya Takeshi , Fujiwara Masachika , Kimura Hirokazu , Takei Hidefumi , Takizawa Hajime
Published: November 2018

A 17‐year‐old woman was referred to our hospital due to cough on exertion and right chest pain over the previous two months, together with bloody sputum over the previous week. Chest X‐ray demonstrated a nodule measuring 3 cm in diameter in the right middle lung field. On repeated bronchoscopy, the tumour was recognized as a rapidly growing intra‐bronchial protruded tumour at the orifice of the right B8. Based on a tentative diagnosis of lung cancer, right lower lobectomy was performed. She was diagnosed with mixed squamous cell and glandular papilloma of the bronchus without smoking history and human papillomavirus infection. Solitary endobronchial papillomas are rare but should be considered a differential diagnosis for solitary lung nodule with the potential to develop into carcinoma.
Highly Reproducible Large‐Area Perovskite Solar Cell Fabrication via Continuous Megasonic Spray Coating of CH3NH3PbI3
Authors: Park Mincheol , Cho Woohyung , Lee Gunhee , Hong Seung Chan , Kim Min‐cheol , Yoon Jungjin , Ahn Namyoung , Choi Mansoo
Published: November 2018

A simple, low‐cost, large area, and continuous scalable coating method is proposed for the fabrication of hybrid organic–inorganic perovskite solar cells. A megasonic spray‐coating method utilizing a 1.7 MHz megasonic nebulizer that could fabricate reproducible large‐area planar efficient perovskite films is developed. The coating method fabricates uniform large‐area perovskite film with large‐sized grain since smaller and narrower sized mist droplets than those generated by existing ultrasonic spray methods could be generated by megasonic spraying. The volume flow rate of the CH3NH3PbI3 precursor solution and the reaction temperature are controlled, to obtain a high quality perovskite active layer. The devices reach a maximum efficiency of 16.9%, with an average efficiency of 16.4% from 21 samples. The applicability of megasonic spray coating to the fabrication of large‐area solar cells (1 cm2), with a power conversion efficiency of 14.2%, is also demonstrated. This is a record high efficiency for large‐area perovskite solar cells fabricated by continuous spray coating.
The Reaction between Mn and Se Layers
Authors: Choffel Marisa A. , Hamann Danielle M. , Joke Jordan A. , Cordova Dmitri Leo M. , Johnson David C.
Published: November 2018

The mechanism of the reaction between Mn and Se is shown to depend on the composition and the thickness of Mn and Se layers. Samples were prepared by modulated elemental reactants (MER) method. The elements were evaporated using either electron beam guns or effusion cells and the total amount of each element was controlled using quartz crystal monitors. Different ratios of the elements and different total amounts of the elements per repeating unit were experimentally explored. Near a one to one ratio of Mn and Se, α‐MnSe crystallizes upon deposition. Compositions near a one to two ratio of Mn to Se proceed through an amorphous intermediate for the layer thicknesses investigated, with MnSe2 crystallizing at 150 °C. Between these compositions, the two bilayer thicknesses explored evolve differently, with films with bilayer thicknesses near 0.5 nm nucleating MnSe, whereas films with bilayer thicknesses around 1 nm nucleating a mixture of MnSe and MnSe2. Samples around 80 % Se formed a previously unreported compound with a small monoclinic unit cell with lattice parameters a = 4.942(2) Å, b = 4.32(3) Å, c = 3.779(1) Å, and β = 90.13(3)°.
Is Global Pediatric Surgery a Good Investment?
Authors: Smith Emily R. , Concepcion Tessa L. , Niemeier Kelli J. , Ademuyiwa Adesoji O.
Published: November 2018

Investing in surgery has been highlighted as integral to strengthening overall health systems and increasing economic prosperity in low‐income and middle‐income countries (LMICs). The provision of surgical care in LMICs not only affects economies on a macro‐level, but also impacts individual families within communities at a microeconomic level. Given that children represent 50% of the population in LMICs and the burden of unmet surgical needs in these areas is high, investing pediatric‐specific components of surgical and anesthesia care is needed. Implementation efforts for pediatric surgical care include incorporating surgery‐specific priorities into the global child health initiatives, improving global health financing for scale‐up activities for children, increasing financial risk protection mechanisms for families of children with surgical needs, and including comprehensive pediatric surgical models of care into country‐level plans.
Free Will and Mental Powers
Authors: van Miltenburg Niels , Ometto Dawa
Published: November 2018

In this paper, we investigate how contemporary metaphysics of powers can further an understanding of agent-causal theories of free will. The recent upsurge of such ontologies of powers and the understanding of causation it affords promises to demystify the notion of an agent-causal power. However, as we arguepace(Mumford and Anjum in Analysis 74:20–25, 2013; Am Philos Q 52:1–12, 2015a), the very ubiquity of powers also poses a challenge to understanding in what sense exercises of an agent’s power to act could still befree—neither determined by external circumstances, nor random, but self-determined. To overcome this challenge, we must understand what distinguishes the power to act from ordinary powers. We suggest this difference lies in itsrationalnature, and argue that existing agent-causal accounts (e.g., O’Connor in Libertarian views: dualist and agent-causal theories, Oxford University Press, Oxford, 2002; Lowe in Personal agency: the metaphysics of mind and action, Oxford University Press, Oxford, 2013) fail to capture the sense in which the power to act is rational. A proper understanding, we argue, requires us to combine the recent idea that the power to act is a ‘two-way power’ (e.g., Steward in A metaphysics for freedom, Oxford University Press, Oxford, 2012b; Lowe (in: Groff, Greco (eds) Powers and capacities in philosophy: the new aristotelianism, Routledge, New York, 2013) with the idea that it is intrinsically rational. We sketch the outlines of an original account that promises to do this. On this picture, what distinguishes the power to act is its specialgenerality—the power to act, unlike ordinary powers, does not come with any one typical manifestation. We argue that this special generality can be understood to be a feature of the capacity toreason. Thus, we argue, an account of agent-causation that can further our understanding of free will requires us to recognize a specifically rational ormentalvariety of power.
Nano-mechanical Behavior of H13 Tool Steel Fabricated by a Selective Laser Melting Method
Authors: Nguyen Van Luong , Kim Eun-ah , Yun Jaecheol , Choe Jungho , Yang Dong-yeol , Lee Hak-sung , Lee Chang-woo , Yu Ji-Hun
Published: November 2018

Nano-mechanical properties of selective laser melted H13 steel at a scan laser speed of 100 mm/s were investigated using nanoindentation tests. The findings shed light on the interrelationship between the nanoindentation strain rate and hardness. It was found that the strain-rate sensitivity exponent (m = 0.022) of this material indicated that the nanoindentation hardness increased in a range of (8.41 to 9.18) GPa with an increase in the strain rate ranging from 0.002 to 0.1 s−1.
Absorption and metabolism of isothiocyanates formed from broccoli glucosinolates: effects of BMI and daily consumption in a randomised clinical trial
Authors: Charron Craig S. , Vinyard Bryan T. , Ross Sharon A. , Seifried Harold E. , Jeffery Elizabeth H. , Novotny Janet A.
Published: November 2018

Sulphoraphane originates from glucoraphanin in broccoli and is associated with anti-cancer effects. A preclinical study suggested that daily consumption of broccoli may increase the production of sulphoraphane and sulphoraphane metabolites available for absorption. The objective of this study was to determine whether daily broccoli consumption alters the absorption and metabolism of isothiocyanates derived from broccoli glucosinolates. We conducted a randomised cross-over human study (n18) balanced for BMI and glutathioneS-transferaseμ1 (GSTM1) genotype in which subjects consumed a control diet with no broccoli (NB) for 16 d or the same diet with 200 g of cooked broccoli and 20 g of raw daikon radish daily for 15 d (daily broccoli, DB) and 100 g of broccoli and 10 g of daikon radish on day 16. On day 17, all subjects consumed a meal of 200 g of broccoli and 20 g of daikon radish. Plasma and urine were collected for 24 h and analysed for sulphoraphane and metabolites of sulphoraphane and erucin by triple quadrupole tandem MS. For subjects with BMI >26 kg/m2(median), plasma AUC and urinary excretion rates of total metabolites were higher on the NB diet than on the DB diet, whereas for subjects with BMI <26 kg/m2, plasma AUC and urinary excretion rates were higher on the DB diet than on the NB diet. Daily consumption of broccoli interacted with BMI but notGSTM1genotype to affect plasma concentrations and urinary excretion of glucosinolate-derived compounds believed to confer protection against cancer. This trial was registered as NCT02346812.
Equity and sustainability in the Anthropocene: a social–ecological systems perspective on their intertwined futures
Authors: Leach Melissa , Reyers Belinda , Bai Xuemei , Brondizio Eduardo S. , Cook Christina , Díaz Sandra , Espindola Giovana , Scobie Michelle , Stafford-Smith Mark , Subramanian Suneetha M
Published: November 2018

Non-technical summary

It is no longer possible nor desirable to address the dual challenges of equity and sustainability separately. Instead, they require new thinking and approaches which recognize their interlinkages, as well as the multiple perspectives and dimensions involved. We illustrate how equity and sustainability are intertwined, and how a complex social–ecological systems lens brings together advances from across the social and natural sciences to show how (in)equity and (un)sustainability are produced by the interactions and dynamics of coupled social–ecological systems. This should help understand which possible pathways could lead to sustainable and fair futures.
DNA Methylation Changes in Whole Blood and CD16+ Neutrophils in Response to Chronic Folic Acid Supplementation in Women of Childbearing Age
Authors: Shade Deanna C. , Park Hea Jin , Hausman Dorothy B. , Hohos Natalie , Meagher Richard B. , Kauwell Gail P. A. , Kilaru Varun , Lewis Richard D. , Smith Alicia K. , Bailey Lynn B.
Published: November 2018

Abstract. Folate, a water-soluble vitamin, is a key source of one-carbon groups for DNA methylation, but studies of the DNA methylation response to supplemental folic acid yield inconsistent results. These studies are commonly conducted using whole blood, which contains a mixed population of white blood cells that have been shown to confound results. The objective of this study was to determine if CD16+ neutrophils may provide more specific data than whole blood for identifying DNA methylation response to chronic folic acid supplementation. The study was performed in normal weight (BMI 18.5 – 24.9 kg/m2) women (18 – 35 y; n = 12), with blood samples taken before and after 8 weeks of folic acid supplementation at 800 μg/day. DNA methylation patterns from whole blood and isolated CD16+ neutrophils were measured across >485,000 CpG sites throughout the genome using the Infinium HumanMethylation450 BeadChip. Over the course of the 8-week supplementation, 6746 and 7513 CpG sites changed (p < 0.05) in whole blood and CD16+ neutrophils, respectively. DNA methylation decreased in 68.4% (whole blood) and 71.8% (CD16+ neutrophils) of these sites. There were only 182 CpG sites that changed in both the whole blood and CD16+ neutrophils, 139 of which changed in the same direction. These results suggest that the genome-wide DNA methylation response to chronic folic acid supplementation is different between whole blood and CD16+ neutrophils and that a single white blood cell type may function as a more specific epigenetic reporter of folate status than whole blood.
Precipitation Changes in a Climate With 2‐K Surface Warming From Large Ensemble Simulations Using 60‐km Global and 20‐km Regional Atmospheric Models
Authors: Fujita M. , Mizuta R. , Ishii M. , Endo H. , Sato T. , Okada Y. , Kawazoe S. , Sugimoto S. , Ishihara K. , Watanabe S.
Published: November 2018

A near‐future, 2‐K warming climate simulation comprising over 3,000 years of ensemble simulations was performed using 60‐km global and 20‐km regional atmospheric models. Even in the +2‐K climate, indices of extreme precipitation and dryness increased significantly in the extratropics compared with the historical climate. Mean precipitation increases in the rainy season and decreases in the dry season, indicating that the seasonal precipitation range becomes amplified with global warming. The intensification of precipitation and dryness from +2 to +4 K was also robust in the mean for climatological wet and arid regions. Around Japan, which was classified as a wet region, the regional atmospheric model predicts that the extreme hourly precipitation in the future climate becomes more extreme on hot days, but slightly weaker on cold days. This extreme precipitation has a high sensitivity to air temperature exceeding 7%/K.
Precipitation of Radiation Belt Electrons by EMIC Waves With Conjugated Observations of NOAA and Van Allen Satellites
Authors: Yuan Zhigang , Liu Kun , Yu Xiongdong , Yao Fei , Huang Shiyong , Wang Dedong , Ouyang Zhihai
Published: November 2018

In this letter, we present unique conjugated satellite observations of MeV relativistic electron precipitation caused by electromagnetic ion cyclotron (EMIC) waves. On the outer boundary of the plasmasphere, the Van Allen probe observed EMIC waves. At ionospheric altitudes, the National Oceanic and Atmospheric Administration (NOAA) 16 satellite at the footprint of Van Allen probe simultaneously detected obvious flux enhancements for precipitating >MeV radiation belt electrons but not for precipitating MeV radiation belt electrons. Our result provides a direct magnetic conjugated observational link between in situ inner magnetospheric EMIC waves and precipitation of MeV relativistic electrons at ionospheric altitudes so as to reveal that EMIC waves can solely scatter MeV radiation belt electrons into the loss cone so as to precipitate into the atmosphere.
Decadal‐Scale Increases of Anthropogenic CO2 in Antarctic Bottom Water in the Indian and Western Pacific Sectors of the Southern Ocean
Authors: Murata Akihiko , Kumamoto Yu‐ichiro , Sasaki Ken‐ichi
Published: November 2018

We determined decadal‐scale increases of anthropogenic CO2 in the water column using data sets collected 17 years apart (1994–1996 and 2012–2013) along a transect at nominal 62°S in the Indian and western Pacific sectors of the Southern Ocean. Large increases of anthropogenic CO2 (up to 9.1 ± 1.5 μmol/kg), closely following atmospheric CO2 increases, were found in Antarctic Bottom Water (AABW), previously considered a small sink of anthropogenic CO2. Vertical distributions of anthropogenic CO2 increases showed significant positive correlations with those of changes in CFC‐12 and SF6, implying that the distributions were mainly controlled by physical processes such as ventilation and circulation. Calculated uptake rates of anthropogenic CO2 by AABW were between 0.29 and 0.39 mol·m−2·yr−1 in five longitudinal segments of the transect. In accounting for the large increase of anthropogenic CO2 in AABW, sea surface conditions in the formation region of AABW are important.
Are Extreme Skew Surges Independent of High Water Levels in a Mixed Semidiurnal Tidal Regime?
Authors: Santamaria‐Aguilar S. , Vafeidis A. T.
Published: November 2018

Based on previous studies of tide‐gauge records from locations with semidiurnal tidal regimes, extreme skew surges are always assumed independent of the high water (HW). However, differences in water depth between HW peaks of semidiurnal tidal regimes can be much lower than those in mixed semidiurnal regimes, where one daily HW is higher than the other. We statistically analyze tide‐gauge records of 15 sites worldwide with a mixed semidiurnal regime and find that for approximately half of these sites extreme skew surges occur more often during smaller HWs. This dependence is not caused by seasonality effects, and the places that show dependence are all located in areas with a shallow continental shelf, thus indicating possible tide‐skew surge interactions. In those cases where dependence exists, using the skew surge does not seem to offer any advantages over the nontidal residual.
Estimates of Present‐Day and Future Climatologies of Freezing Rain in Europe Based on CORDEX Regional Climate Models
Authors: Kämäräinen Matti , Hyvärinen Otto , Vajda Andrea , Nikulin Grigory , Meijgaard Erik van , Teichmann Claas , Jacob Daniela , Gregow Hilppa , Jylhä Kirsti
Published: November 2018

The effects of climate change on freezing rain in Europe under medium (RCP4.5) and strong (RCP8.5) future emission scenarios were assessed using seven regional climate model simulations conducted within the World Climate Research Project's COordinated Regional climate Downscaling Experiment over the European Domain (EURO‐CORDEX). A precipitation‐typing algorithm was applied to modeled three‐dimensional subdaily time series of key meteorological variables to estimate the occurrence and amounts of freezing rain above selected intensity thresholds. The annual probabilities of freezing rain during the baseline (1971–2000) and future (2071–2100) periods were calculated. The models agree that under the RCP8.5 scenario, the frequencies of freezing rain decrease in western, central, and southeastern Europe by 20–55% and increase in the northern and northeastern parts of the continent by 0–50% toward the end of the century. In the northern regions, the peaks in spring and fall with freezing rain amounts during the baseline period tend to merge to a single peak in winter during the future period. Under the RCP4.5 scenario, the changes are qualitatively similar but smaller.
Influence of Central Siberian Snow‐Albedo Feedback on the Spring East Asian Dust Cycle and Connection With the Preceding Winter Arctic Oscillation
Authors: Liu Heng , Liu Xiaodong , Dong Buwen
Published: November 2018

The Asian dust cycle has significant effects on the climate and environment, while its spatiotemporal variability and change mechanisms are not yet completely understood. Reanalysis data from the Modern‐Era Retrospective Analysis for Research and Applications, version 2 (MERRA2), data set are used to explore the spatiotemporal distribution of the East Asian dust cycle and possible reasons for the interannual variations. Based on the empirical orthogonal function analysis, the dominant mode of dust emissions from the East Asian deserts in the dust season (spring) shows that the Gobi Desert contributes most of the interannual variance of dust emissions in East Asia. The patterns of the regional circulation, temperature, and radiation are analyzed by regressing these variables against the principal component time series of the first empirical orthogonal function mode. The results show that the enhanced dust emissions are associated with a cyclonic circulation anomaly and cooling in the lower and middle troposphere over Central Siberia. The cooling is attributed to local snow‐albedo and cloud‐albedo feedbacks. The surface cooling is conducive to maintain the snow cover, whereas the cooling in the middle troposphere is associated with the increase of the relative humidity and cloud cover. The increased snow and cloud cover reflect more shortwave radiation, tending to maintain or amplify the surface cooling. It is also found that the negative phase of the Arctic Oscillation in winter initiates the surface cooling in the next spring and results in positive snow‐albedo and cloud feedbacks in Central Siberia, eventually enhancing the East Asian dust cycle.
Rock Abundance and Crater Density in the Candidate Chang'E‐5 Landing Region on the Moon
Authors: Wu Bo , Huang Jun , Li Yuan , Wang Yiran , Peng Jin
Published: November 2018

Chang'E‐5 is China's first lunar sample‐return mission, which will be launched in 2019. Understanding the distribution of rocks and craters in the candidate landing region is important for selecting suitable landing sites and studying the surface geology. This paper first separately investigates rock abundance and crater density in the candidate landing region, then provides a joint analysis of them, for the purposes of identifying potential hazards for safe landing and their geological implications. The results indicate that in the region, rocks are mostly concentrated around rocky ejecta craters. About 90% of the region has a rock abundance (the fractional area covered by rocks) of less than 1%. The average crater density is about 250 craters (≥ 100 m in diameter) per 100 km2; on average, 13.5% of the region is covered by craters. The surface ages of geologic units in the region estimated using crater size‐frequency distribution indicate that the eastern part of the region is younger than the western part. The joint analysis of rock abundance and crater density identifies local areas that are relatively unfavorable for safe landing. The joint analysis also indicates an exponential relationship between overall rock abundance and crater density, and a roughly linear relationship between overall rock abundance and surface age. Furthermore, the joint analysis indicates an inverse correlation between rock abundance and the relative maturation of craters. The presented research and results will be helpful for identifying suitable landing sites for the Chang'E‐5 lander. They also provide fresh insights into lunar surface geology.
Multiproxy Isotopic and Geochemical Analysis of the Siwalik Sediments in NW India: Implication for the Late Cenozoic Tectonic Evolution of the Himalaya
Authors: Mandal Sanjay Kumar , Scherler Dirk , Romer Rolf L. , Burg Jean‐Pierre , Guillong Marcel , Schleicher Anja M.
Published: November 2018

Provenance analysis of the Sub‐Himalayan Late Miocene‐Pleistocene foreland basin deposits (Siwaliks) from the Dehradun reentrant area provides a 10‐Myr long record of the denudation history and tectonic evolution of the northwestern Indian Himalaya. We studied Siwalik sediments exposed along the Mohand‐Rao and Haripur‐Khol sections, using detrital zircon U‐Pb geochronology, major and trace elements, and Sr‐Nd isotope geochemistry. Results suggest that the erosion pattern has been relatively stable since the Late Miocene with sediments derived from the Tethyan Himalayan (THS), Greater Himalayan (GHS), and outer‐ (oLHS) and inner‐Lesser Himalayan (iLHS) sequences. Provenance data indicate that erosional unroofing of the Lesser Himalayan Crystalline sequences (LHCS) initiated around 6 Ma, possibly related to out‐of‐sequence movement of the Ramgarh‐Munsiari Thrust. Our data also suggest erosional recycling of older foreland basin deposits into younger Siwaliks since ~5.5 Ma, which may indicate the time of thrust propagation from the Lesser Himalaya into the foreland basin. While the iLHS has been exposed to erosion since at least ~10 Ma, the Siwaliks were dominated by materials derived from the GHS and THS sources. We interpret these results as an indication that tectonic uplift and erosion of the orogenic wedge occurred in response to duplexing of the iLHS and concomitant high topography and rock uplift rate in the Greater and Tethyan Himalaya. Comparing the provenance of the Siwalik sediments with that of the modern Ganga and Yamuna river sediments further indicates that deposition during the Late Cenozoic was most likely accomplished by southward flowing transverse Himalayan rivers, analogous to the modern ones.
Resuscitation of anammox bacteria after >10,000 years of dormancy
Authors: Zhu Guibing , Wang Shanyun , Wang Cheng , Zhou Liguang , Zhao Siyan , Li Yixiao , Li Fangbai , Jetten Mike S M , Lu Yonglong , Schwark Lorenz
Published: November 2018

Water is essential for life on Earth, and an important medium for microbial energy and metabolism. Dormancy is a state of low metabolic activity upon unfavorable conditions. Many microorganisms can switch to a metabolically inactive state after water shortage, and recover once the environmental conditions become favorable again. Here, we resuscitated dormant anammox bacteria from dry terrestrial ecosystems after a resting period of >10 ka by addition of water without any other substrates. Isotopic-tracer analysis showed that water induced nitrate reduction yielding sufficient nitrite as substrate and energy for activating anammox bacteria. Subsequently, dissimilatory nitrate reduction to ammonium (DNRA) provided the substrate ammonium for anammox bacteria. The ammonium and nitrite formed were used to produce dinitrogen gas. High throughput sequencing and network analysis identified Brocadia as the dominant anammox species and a Jettenia species seemed to connect the other community members. Under global climate change, increasing precipitation and soil moisture may revive dormant anammox bacteria in arid soils and thereby impact global nitrogen and carbon cycles.
Enhanced fear memories and brain glucose metabolism (18F-FDG-PET) following sub-anesthetic intravenous ketamine infusion in Sprague-Dawley rats
Authors: Radford Kennett D. , Park Thomas Y. , Jaiswal Shalini , Pan Hongna , Knutsen Andrew , Zhang Michael , Driscoll Mercedes , Osborne-Smith Lisa A. , Dardzinski Bernard J. , Choi Kwang H.
Published: November 2018

Ketamine is a multimodal dissociative anesthetic, which provides powerful analgesia for victims with traumatic injury. However, the impact of ketamine administration in the peri-trauma period on the development of post-traumatic stress disorder (PTSD) remains controversial. Moreover, there is a major gap between preclinical and clinical studies because they utilize different doses and routes of ketamine administration. Here, we investigated the effects of sub-anesthetic doses of intravenous (IV) ketamine infusion on fear memory and brain glucose metabolism (BGluM) in rats. Male Sprague-Dawley rats received an IV ketamine infusion (0, 2, 10, and 20 mg/kg, 2 h) or an intraperitoneal (IP) injection (0 and 10 mg/kg) following an auditory fear conditioning (3 pairings of tone and foot shock [0.6 mA, 1 s]) on day 0. Fear memory retrieval, fear extinction, and fear recall were tested on days 2, 3, and 4, respectively. The effects of IV ketamine infusion (0 and 10 mg/kg) on BGluM were measured using 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT). The IV ketamine infusion dose-dependently enhanced fear memory retrieval, delayed fear extinction, and increased fear recall in rats. The IV ketamine (10 mg/kg) increased BGluM in the hippocampus, amygdala, and hypothalamus, while decreasing it in the cerebellum. On the contrary, a single ketamine injection (10 mg/kg, IP) after fear conditioning facilitated fear memory extinction in rats. The current findings suggest that ketamine may produce differential effects on fear memory depending on the route and duration of ketamine administration.
STING-dependent sensing of self-DNA drives silica-induced lung inflammation
Authors: Benmerzoug Sulayman , Rose Stéphanie , Bounab Badreddine , Gosset David , Duneau Laure , Chenuet Pauline , Mollet Lucile , Le Bert Marc , Lambers Christopher , Geleff Silvana , Roth Michael , Fauconnier Louis , Sedda Delphine , Carvalho Clarisse , Perche Olivier , Laurenceau David , Ryffel Bernhard , Apetoh Lionel , Kiziltunc Ahmet , Uslu Hakan , Albez Fadime Sultan , Akgun Metin , Togbe Dieudonnée , Quesniaux Valerie F. J.
Published: November 2018

Silica particles induce lung inflammation and fibrosis. Here we show that stimulator of interferon genes (STING) is essential for silica-induced lung inflammation. In mice, silica induces lung cell death and self-dsDNA release in the bronchoalveolar space that activates STING pathway. Degradation of extracellular self-dsDNA by DNase I inhibits silica-induced STING activation and the downstream type I IFN response. Patients with silicosis have increased circulating dsDNA and CXCL10 in sputum, and patients with fibrotic interstitial lung disease display STING activation and CXCL10 in the lung. In vitro, while mitochondrial dsDNA is sensed by cGAS-STING in dendritic cells, in macrophages extracellular dsDNA activates STING independent of cGAS after silica exposure. These results reveal an essential function of STING-mediated self-dsDNA sensing after silica exposure, and identify DNase I as a potential therapy for silica-induced lung inflammation.
Hierarchical and programmable one-pot synthesis of oligosaccharides
Authors: Cheng Cheng-Wei , Zhou Yixuan , Pan Wen-Harn , Dey Supriya , Wu Chung-Yi , Hsu Wen-Lian , Wong Chi-Huey
Published: November 2018

The programmable one-pot oligosaccharide synthesis method was designed to enable the rapid synthesis of a large number of oligosaccharides, using the software Optimer to search Building BLocks (BBLs) with defined relative reactivity values (RRVs) to be used sequentially in the one-pot reaction. However, there were only about 50 BBLs with measured RRVs in the original library and the method could only synthesize small oligosaccharides due to the RRV ordering requirement. Here, we increase the library to include 154 validated BBLs and more than 50,000 virtual BBLs with predicted RRVs by machine learning. We also develop the software Auto-CHO to accommodate more data handling and support hierarchical one-pot synthesis using fragments as BBLs generated by the one-pot synthesis. This advanced programmable one-pot method provides potential synthetic solutions for complex glycans with four successful examples demonstrated in this work.
Why rankings of biomedical image analysis competitions should be interpreted with care
Authors: Maier-Hein Lena , Eisenmann Matthias , Reinke Annika , Onogur Sinan , Stankovic Marko , Scholz Patrick , Arbel Tal , Bogunovic Hrvoje , Bradley Andrew P. , Carass Aaron , Feldmann Carolin , Frangi Alejandro F. , Full Peter M. , van Ginneken Bram , Hanbury Allan , Honauer Katrin , Kozubek Michal , Landman Bennett A. , März Keno , Maier Oskar , Maier-Hein Klaus , Menze Bjoern H. , Müller Henning , Neher Peter F. , Niessen Wiro , Rajpoot Nasir , Sharp Gregory C. , Sirinukunwattana Korsuk , Speidel Stefanie , Stock Christian , Stoyanov Danail , Taha Abdel Aziz , van der Sommen Fons , Wang Ching-Wei , Weber Marc-André , Zheng Guoyan , Jannin Pierre , Kopp-Schneider Annette
Published: November 2018

International challenges have become the standard for validation of biomedical image analysis methods. Given their scientific impact, it is surprising that a critical analysis of common practices related to the organization of challenges has not yet been performed. In this paper, we present a comprehensive analysis of biomedical image analysis challenges conducted up to now. We demonstrate the importance of challenges and show that the lack of quality control has critical consequences. First, reproducibility and interpretation of the results is often hampered as only a fraction of relevant information is typically provided. Second, the rank of an algorithm is generally not robust to a number of variables such as the test data used for validation, the ranking scheme applied and the observers that make the reference annotations. To overcome these problems, we recommend best practice guidelines and define open research questions to be addressed in the future.
Metabolite changes in blood predict the onset of tuberculosis
Authors: Weiner January , Maertzdorf Jeroen , Sutherland Jayne S. , Duffy Fergal J. , Thompson Ethan , Suliman Sara , McEwen Gayle , Thiel Bonnie , Parida Shreemanta K. , Zyla Joanna , Hanekom Willem A. , Mohney Robert P. , Boom W. Henry , Mayanja-Kizza Harriet , Howe Rawleigh , Dockrell Hazel M. , Ottenhoff Tom H. M. , Scriba Thomas J. , Zak Daniel E. , Walzl Gerhard , Kaufmann Stefan H. E. ,   The GC6-74 consortium, Abebe Almaz , Abel Brian , Adegbola Richard , Adetifa Ifedayo , Ambrose Lyn , Andersen Peter , Antonio Martin , Aseffa Abraham , van Baarle Debbie , Barker Lew , Bekele Yonas , Bilek Nicole , Black Gillian F. , Bowmaker Mark , Branson Keith , Brennan Michael , Chegou Novel N. , Chilongo Femia , Chung William Kwong , Corrah Tumani , Crampin Ameilia C. , Doherty Mark , Dolganov Gregory , Donkor Simon , Downing Katrina , Fisher Michelle , Franken Kees L. M. C. , French Neil , Geiter Larry , Geluk Annemieke , Golinski Robert , Gorak-Stolinska Patricia , Haks Marielle C. , Hill Philip , Hughes Jane , Hur Yun-Gyoung , Iwnetu Rachel , Jacobson Marc , Joloba Moses , Joosten Simone A. , Kagina Benjamin , Kassa Desta , Kisingo Hussein , Klein Michel R. , Kriel Magdalena , Lalor Maeve , Lee Ji-Sook , Loxton Andre G. , Mahomed Hassan , van Meijgaarden Krista E. , Mesele Tsehayenesh , Miedema Frank , Mihret Adane , Mulenga Humphrey , Muller Stefanie , Mvula Hazzie , Nene Nonhlanhla , Ngwira Bagrey , Nsereko Mary , Okwera Brenda , Ota Martin , Penn-Nicholson Adam , Du Plessis Nelita , Ramachandran S. , Rosenkrands Ida , Sadoff Jerry , Saul Jacky , Schoolnik Gary , Simukonda Felanji , Sizemore Donata , Smith Steven , Ben Smith Anne , van der Spuy Gian , Stanley Kim , Tabb David , Tafesse Mesfin , Tegbaru Belete , Togun Toyin , Tromp Gerhardus , Van Tran , Watkins Kate , Weichold Frank , Weldingh Karin , Yamuah Lawrence , Zalwango Sarah
Published: November 2018

New biomarkers of tuberculosis (TB) risk and disease are critical for the urgently needed control of the ongoing TB pandemic. In a prospective multisite study across Subsaharan Africa, we analyzed metabolic profiles in serum and plasma from HIV-negative, TB-exposed individuals who either progressed to TB 3–24 months post-exposure (progressors) or remained healthy (controls). We generated a trans-African metabolic biosignature for TB, which identifies future progressors both on blinded test samples and in external data sets and shows a performance of 69% sensitivity at 75% specificity in samples within 5 months of diagnosis. These prognostic metabolic signatures are consistent with development of subclinical disease prior to manifestation of active TB. Metabolic changes associated with pre-symptomatic disease are observed as early as 12 months prior to TB diagnosis, thus enabling timely interventions to prevent disease progression and transmission.
Minimizing the electrosorption of water from humid ionic liquids on electrodes
Authors: Bi Sheng , Wang Runxi , Liu Shuai , Yan Jiawei , Mao Bingwei , Kornyshev Alexei A. , Feng Guang
Published: November 2018

In supercapacitors based on ionic liquid electrolytes, small amounts of absorbed water could potentially reduce the electrochemical window of electrolytes and cause performance degradation. The same would take place if ionic liquids are used as solvents for electrocatalysis involving the dissolved molecular species. In this work, we carry out molecular dynamics simulations, with gold and carbon electrodes in typical ionic liquids, hydrophobic and hydrophilic, to study electrosorption of water. We investigate the effects of hydrophobicity/hydrophilicity of ionic liquids and electrodes on interfacial distribution of ions and electrosorbed water. Results reveal that using hydrophilic ionic liquids would help to keep water molecules away from the negatively charged electrodes, even at large electrode polarizations. This conclusion is supported by electrochemical cyclic voltammetry measurements on gold and carbon electrodes in contact with humid ionic liquids. Thereby, our findings suggest potential mechanisms for protection of electrodes from water electrosorption.
The two-fluid dynamics and energetics of the asymmetric magnetic reconnection in laboratory and space plasmas
Authors: Yamada M. , Chen L.-J. , Yoo J. , Wang S. , Fox W. , Jara-Almonte J. , Ji H. , Daughton W. , Le A. , Burch J. , Giles B. , Hesse M. , Moore T. , Torbert R.
Published: November 2018

Magnetic reconnection is a fundamental process in magnetized plasma where magnetic energy is converted to plasma energy. Despite huge differences in the physical size of the reconnection layer, remarkably similar characteristics are observed in both laboratory and magnetosphere plasmas. Here we present the comparative study of the dynamics and physical mechanisms governing the energy conversion in the laboratory and space plasma in the context of two-fluid physics, aided by numerical simulations. In strongly asymmetric reconnection layers with negligible guide field, the energy deposition to electrons is found to primarily occur in the electron diffusion region where electrons are demagnetized and diffuse. A large potential well is observed within the reconnection plane and ions are accelerated by the electric field toward the exhaust region. The present comparative study identifies the robust two-fluid mechanism operating in systems over six orders of magnitude in spatial scales and over a wide range of collisionality.
Phase diagram of Bi2Sr2CaCu2O8+δ revisited
Authors: Drozdov I. K. , Pletikosić I. , Kim C.-K. , Fujita K. , Gu G. D. , Davis J. C. Séamus , Johnson P. D. , Božović I. , Valla T.
Published: November 2018

In cuprate superconductors, the doping of carriers into the parent Mott insulator induces superconductivity and various other phases whose characteristic temperatures are typically plotted versus the doping level p. In most materials, p cannot be determined from the chemical composition, but it is derived from the superconducting transition temperature, Tc, using the assumption that the Tc dependence on doping is universal. Here, we present angle-resolved photoemission studies of Bi2Sr2CaCu2O8+δ, cleaved and annealed in vacuum or in ozone to reduce or increase the doping from the initial value corresponding to Tc = 91 K. We show that p can be determined from the underlying Fermi surfaces and that in-situ annealing allows mapping of a wide doping regime, covering the superconducting dome and the non-superconducting phase on the overdoped side. Our results show a surprisingly smooth dependence of the inferred Fermi surface with doping. In the highly overdoped regime, the superconducting gap approaches the value of 2Δ0 = (4 ± 1)kBTc
Single-molecule imaging correlates decreasing nuclear volume with increasing TF-chromatin associations during zebrafish development
Authors: Reisser Matthias , Palmer Anja , Popp Achim P. , Jahn Christopher , Weidinger Gilbert , Gebhardt J. Christof M.
Published: November 2018

Zygotic genome activation (ZGA), the onset of transcription after initial quiescence, is a major developmental step in many species, which occurs after ten cell divisions in zebrafish embryos. How transcription factor (TF)-chromatin interactions evolve during early development to support ZGA is largely unknown. We establish single molecule tracking in live developing zebrafish embryos using reflected light-sheet microscopy to visualize two fluorescently labeled TF species, mEos2-TBP and mEos2-Sox19b. We further develop a data acquisition and analysis scheme to extract quantitative information on binding kinetics and bound fractions during fast cell cycles. The chromatin-bound fraction of both TFs increases during early development, as expected from a physical model of TF-chromatin interactions including a decreasing nuclear volume and increasing DNA accessibility. For Sox19b, data suggests the increase is mainly due to the shrinking nucleus. Our single molecule approach provides quantitative insight into changes of TF-chromatin associations during the developmental period embracing ZGA.
Empirical modeling of dopability in diamond-like semiconductors
Authors: Miller Samuel A. , Dylla Maxwell , Anand Shashwat , Gordiz Kiarash , Snyder G. Jeffrey , Toberer Eric S.
Published: November 2018

Carrier concentration optimization has been an enduring challenge when developing newly discovered semiconductors for applications (e.g., thermoelectrics, transparent conductors, photovoltaics). This barrier has been particularly pernicious in the realm of high-throughput property prediction, where the carrier concentration is often assumed to be a free parameter and the limits are not predicted due to the high computational cost. In this work, we explore the application of machine learning for high-throughput carrier concentration range prediction. Bounding the model within diamond-like semiconductors, the learning set was developed from experimental carrier concentration data on 127 compounds ranging from unary to quaternary. The data were analyzed using various statistical and machine learning methods. Accurate predictions of carrier concentration ranges in diamond-like semiconductors are made within approximately one order of magnitude on average across both p- and n-type dopability. The model fit to empirical data is analyzed to understand what drives trends in carrier concentration and compared with previous computational efforts. Finally, dopability predictions from this model are combined with high-throughput quality factor predictions to identify promising thermoelectric materials.
The hydrogen-induced pitting corrosion mechanism in duplex stainless steel studied by current-sensing atomic force microscopy
Authors: Yakubov Vladislav , Lin Meichao , Volinsky Alex A. , Qiao Lijie , Guo Liqiu
Published: November 2018

Duplex stainless steels have excellent corrosion resistance due to their two-phase microstructure and electrically insulating passive film. Nevertheless, hydrogen charging causes deterioration of the corrosion protection mechanisms, resulting in increased pitting susceptibility. In this study, current-sensing atomic force microscopy was used to investigate the electrical properties of the passive film formed on 2507 duplex stainless steel before hydrogen charging. Results were compared with optical images of pitting corrosion initiation after hydrogen charging and FeCl3 exposure. Highest passive film conductivity and current density were seen at grain boundaries, indicating poor passive film development and high pitting probability. High conductivity was also observed on the passive film located at the adjacent austenite phase, alluding to favorable conditions for pitting corrosion propagation. Phases were identified by magnetic force microscopy, while pit initiation with subsequent propagation after hydrogen charging and FeCl3 exposure was observed using optical microscopy. Pitting corrosion initiated at grain boundaries and propagated into the austenite grains. This study identified the pitting initiation and propagation mechanisms in 2507 duplex stainless steel.
Fall webworm genomes yield insights into rapid adaptation of invasive species
Authors: Wu Ningning , Zhang Sufang , Li Xiaowei , Cao Yanghui , Liu Xiaojing , Wang Qinghua , Liu Qun , Liu Huihui , Hu Xiao , Zhou Xuguo J. , James Anthony A. , Zhang Zhen , Huang Yongping , Zhan Shuai
Published: November 2018

Invasive species cause considerable ecological and economic damage. Despite decades of broad impacts of invasives on diversity and agriculture, the genetic adaptations and near-term evolution of invading populations are poorly understood. The fall webworm,Hyphantria cunea, a highly successful invasive species that originated in North America, spread throughout the Northern Hemisphere during the past 80 years. Here, we use whole-genome sequencing of invasive populations and transcriptome profiling to probe the underlying genetic bases for the rapid adaptation of this species to new environments and host plants. We find substantial reductions in genomic diversity consistent with founder effects. Genes and pathways associated with carbohydrate metabolism and gustatory receptors are substantially expanded in the webworm genome and show strong signatures of functional polymorphisms in the invasive population. We also find that silk-yielding-associated genes maintained a relatively low level of functional diversity, and identify candidate genes that may regulate the development of silk glands in fall webworms. These data suggest that the fall webworm’s ability to colonize novel hosts, mediated by plasticity in their gustatory capabilities along with an increased ability to utilize novel nutrition sources and substrates, has facilitated the rapid and successful adaptation of the species throughout its range.