bluuebunny/crossref_metadata_2025 huggingface dataset:
Digging for top squarks from Higgs data: from signal strengths to differential distributions
Authors: Banfi Andrea , Bond Andrew , Martin Adam , Sanz Verónica
Published: November 2018

Abstract

One way to hunt for top squarks is to look for deviations from the Standard Model in loop level processes involving Higgses. This method is indirect, but complementary to direct searches as it does not rely on specific top squark decays. Studying inclusive Higgs production pp → h alone is insufficient, since there are parameter regions where the effects of the two top squarks approximately cancel. This degeneracy can be broken by looking at the rate for highly boosted Higgses recoiling against a jet, pp → h + jet. In this paper we perform a detailed study of the complementarity of the inclusive and highly boosted processes at the LHC, both in existing Run 1 and Run 2 data, and looking forward to high luminosity. To break the degeneracy, our calculation must maintain the full mass dependence in the loop functions and therefore cannot be recast in an effective field theory framework. We quantify the dependence of both topologies in the top squark parameter space, and outline which levels of experimental and theoretical understanding would be needed for boosted Higgses to be competitive with inclusive Higgs production.
Entwicklung des Bedarfs an schneller Regelleistung im europäischen Verbundsystem
Authors: Gawlik Wolfgang , Kerdegarbakhsh Alireza , Pešek Markus , Alács Christian
Published: November 2018

Über leistungselektronische Konverter an das Verbundsystem angebundene Einspeiser stellen, anders als direkt angebundene Synchrongeneratoren, keine rotierende Masse für das Verbundsystem zur Verfügung. Das bedeutet, dass sich die Dynamik im schwingungsfähigen Verbundsystem grundsätzlich und in den kommenden Jahren in immer stärkerem Ausmaß verändern wird. Je kleiner die Schwungmasse ist, desto schneller ändert sich die Frequenz bei einem Ungleichgewicht zwischen Erzeugung und Verbrauch. Zur Aktivierung von Regelreserven bleibt damit weniger Zeit, bis kritische Frequenzwerte erreicht werden, bei denen die Integrität des Verbundsystems nicht mehr gewährleistet werden kann. Diese Arbeit beschäftigt sich mit der Betrachtung von schnellerer Regelleistung im Zusammenspiel mit der Schwungmasse im System. Zur Gewährleistung einer ausreichenden Frequenzstabilität im Verbundsystem ergeben sich drei Lösungsansätze, die auf der schnelleren Bereitstellung von Regelleistung basieren: Sicherstellung einer ausreichend großen reellen Schwungmasse, Einspeisung von zusätzlicher Erzeugungsleistung basierend auf dem Frequenzgradienten $df/dt$
d
f
/
d
t
und schnellere Einspeisung von zusätzlicher Erzeugungsleistung basierend auf der Frequenzabweichung $\Delta f$
Δ
f
. Der Bedarf hängt neben den vorauszusetzenden Systemeigenschaften von der Zusammensetzung und Parametrierung dieser Regelleistungen ab.
Activation of silent biosynthetic pathways and discovery of novel secondary metabolites in actinomycetes by co-culture with mycolic acid-containing bacteria
Authors: Hoshino Shotaro , Onaka Hiroyasu , Abe Ikuro
Published: November 2018

Bacterial secondary metabolites (SM) are rich sources of drug leads, and in particular, numerous metabolites have been isolated from actinomycetes. It was revealed by recent genome sequence projects that actinomycetes harbor much more secondary metabolite-biosynthetic gene clusters (SM-BGCs) than previously expected. Nevertheless, large parts of SM-BGCs in actinomycetes are dormant and cryptic under the standard culture conditions. Therefore, a widely applicable methodology for cryptic SM-BGC activation is required to obtain novel SM. Recently, it was discovered that co-culturing with mycolic-acid-containing bacteria (MACB) widely activated cryptic SM-BGCs in actinomycetes. This “combined-culture” methodology (co-culture methodology using MACB as the partner of actinomycetes) is easily applicable for a broad range of actinomycetes, and indeed, 33 novel SM have been successfully obtained from 12 actinomycetes so far. In this review, the development, application, and mechanistic analysis of the combined-culture method were summarized.
SHUN 舜 AND THE INTERPRETATION OF EARLY ORTHOGRAPHICAL VARIATION
Authors: Smith Jonathan M.
Published: November 2018

Ji Xusheng's 季旭昇 account of the character 〈舜〉 as a derivative of 〈夋〉 and ultimately of 〈允〉 by reference to Warring States excavated manuscript evidence, recently elaborated by Adam Smith in these pages, appears to clear up the mystery of Shun's 舜 doppelgänger—Jun 俊—in the Shanhai jing 山海經. However, while Ji's observations are of value, there is danger in treating early orthographical variation of this kind with one eye on an interpretive problem from the received texts. In this case, attested variation shows clearly that the form 〈舜〉 was no such derivative, its peculiar origins arguably “large and useless” from a textual critical point view.
ZHANG ZHONGPEI 張忠培 (1934–2017)
Authors: Linduff Katheryn
Published: November 2018

Professor Zhang Zhongpei was a field archeologist, a Professor of archaeology at Jilin University, and a highly valued Ph.D. director of scores of students. He served in many influential capacities including as the Director of the Palace Museum in Beijing. Among archaeologists he is known through his many publications on regional cultures and through his twenty-year membership on the State Bureau of Cultural Relics which granted permits for archaeological projects that reshaped our understanding of the emergence of Chinese civilization. Zhang Zhongpei passed away at the age of eighty-three on July 3, 2017 in Beijing.
Turbulent duct flow with polymers
Authors: Shahmardi Armin , Zade Sagar , Ardekani Mehdi N. , Poole Rob J. , Lundell Fredrik , Rosti Marco E. , Brandt Luca
Published: November 2018

We have performed direct numerical simulation of the turbulent flow of a polymer solution in a square duct, with the FENE-P model used to simulate the presence of polymers. First, a simulation at a fixed moderate Reynolds number is performed and its results compared with those of a Newtonian fluid to understand the mechanism of drag reduction and how the secondary motion, typical of the turbulent flow in non-axisymmetric ducts, is affected by polymer additives. Our study shows that the Prandtl’s secondary flow is modified by the polymers: the circulation of the streamwise main vortices increases and the location of the maximum vorticity moves towards the centre of the duct. In-plane fluctuations are reduced while the streamwise ones are enhanced in the centre of the duct and dumped in the corners due to a substantial modification of the quasi-streamwise vortices and the associated near-wall low- and high-speed streaks; these grow in size and depart from the walls, their streamwise coherence increasing. Finally, we investigated the effect of the parameters defining the viscoelastic behaviour of the flow and found that the Weissenberg number strongly influences the flow, with the cross-stream vortical structures growing in size and the in-plane velocity fluctuations reducing for increasing flow elasticity.
Outflows in the Seyfert 2 galaxy NGC 5643 traced by the [S iii] emission
Authors: Riffel Rogemar A. , Hekatelyne C. , Freitas Izabel C.
Published: November 2018

We use Gemini Multi-Object Spectrograph integral Field Unit observations of the inner 285 × 400 pc2 region of the Seyfert 2 galaxy NGC 5643 to map the [S iii]λ9069 emission line flux distribution and kinematics, as well as the stellar kinematics, derived by fitting the Ca iiλλλ8498,8542,8662 triplet, at a spatial resolution of 45 pc. The stellar velocity field shows regular rotation, with a projected velocity of 100 km s−1 and kinematic major axis along a position angle of –36°. A ring of low stellar velocity dispersion values (∼70 km s−1), attributed to young/intermediate age stellar populations, is seen surrounding the nucleus with a radius of 50 pc. We found that the [S iii] flux distribution shows an elongated structure along the east–west direction and its kinematics is dominated by outflows within a bi-cone at an ionised gas outflow rate of 0.3 M⊙ yr−1. In addition, velocity slices across the [S iii]λ9069 emission line reveal a kinematic component attributed to rotation of gas in the plane of the galaxy.
Observing merger trees in a new light
Authors: Poulton Rhys J. J. , Robotham Aaron S. G. , Power Chris , Elahi Pascal J.
Published: November 2018

Merger trees harvested from cosmologicalN-body simulations encode the assembly histories of dark matter halos over cosmic time and are a fundamental component of semi-analytical models of galaxy formation. The ability to compare the tools used to construct merger trees, namely halo finders and tree building algorithms, in an unbiased and systematic manner is critical to assess the quality of merger trees. In this paper, we present the dendrogram, a novel method to visualise merger trees, which provides a comprehensive characterisation of a halo’s assembly history—tracking subhalo orbits, halo merger events, and the general evolution of halo properties. We show the usefulness of thedendrogramas a diagnostic tool of merger trees by comparing halo assembly simulation analysed with three different halo finders—VELOCIraptor, AHF, and Rockstar—and their associated tree builders. Based on our analysis of the resulting dendrograms, we highlight how they have been used to motivate improvements to VELOCIraptor. Thedendrogramsoftware is publicly available online, at:https://github.com/rhyspoulton/MergerTree-Dendrograms.
Do Elections Improve Constituency Responsiveness? Evidence from US Cities
Authors: Christensen Darin , Ejdemyr Simon
Published: November 2018

Do elections motivate incumbent politicians to serve their voters? In this paper, we use millions of service requests placed by residents in US cities to measure constituency responsiveness. We then test whether an unusual policy change in New York City, which enabled city councilors to run for three rather than two terms in office, improved constituency responsiveness in previously term-limited councilors’ districts. Using difference-in-differences, we find robust evidence for this. Taking advantage of differential timing of local election races in New York City and San Francisco, we also find late-term improvements to responsiveness in districts represented by reelection-seeking incumbents. Elections improve municipal services, but also create cycles in constituency responsiveness. These findings have implications for theories of representative democracy.
THE HUNCHAKIAN REVOLUTIONARY PARTY AND THE ASSASSINATION ATTEMPTS AGAINST PATRIARCH KHOREN ASHEKIAN AND MAKSUDZADE SIMON BEY IN 1894
Authors: Ketsemanian Varak
Published: November 2018

The spring of 1894 was an important period for Constantinople's Armenian community. Two assassination attempts targeted the Armenian patriarch Khoren Ashekian, and the chairperson of the Armenian Political Assembly Maksudzade Simon Bey, respectively. In both cases, the assailants were partisans of the Hunchakian Party, an Armenian revolutionary organization established in 1887. Analyzing the reasons behind these two attacks, and the imperial context in which they took place, this article challenges aspects of mainstream Armenian and Turkish historiography on the Hamidian period. It argues that a critical look at these two attacks through a socio-economic paradigm rather than an ethno-political one provides a viable analytical framework for deconstructing the notion of the “Armenian millet” as an undifferentiated community. More generally, the article explores the role of violence in shaping intracommunal relationships in the early 1890s.
Yield and nutrient gap analysis for potato in northwest China
Authors: Liu X. , Li S. , He P. , Zhang P. , Duan Y.
Published: November 2018

Analysis of the potato yield gap and the corresponding nutrient gap can help in devising strategies and measurements to increase productivity for closing the gaps through improved practices. On-farm experiments conducted in the main potato production areas of northwest China were used to determine attainable yield. Official statistical data were used to determine the actual on-farm yield. Yield gap was the difference between attainable yield and actual on-farm yield. Nutrient gap was calculated by dividing the size of yield gap by partial factor productivity. Results indicated that nitrogen (N), phosphorus (P) and potassium (K) fertilization increased potato yield by an average of 1169–7625, 2937–5336 and 2331–7338 kg/ha, respectively. The maximum attainable yields (the 90th percentile yields) were 50 145, 37 855, 30 261 and 56 616 kg/ha and the average actual on-farm yield were 14 179, 16 732, 10 271 and 19 990 kg/ha in the Inner Mongolia Autonomous Region (IMAR), Gansu, Ningxia and Qinghai provinces, respectively. In the above four regions, yield would need to increase by 165, 70, 112 and 121% from actual yield to reach 75% of attainable yield. Compared with recent 3-year average NPK rates by farmers, the total NPK rates need to increase by 90.1–134.3% for IMAR, 42.9–69.2% for Gansu, 68.1–111.2% for Ningxia and 48.1–83.8% for Qinghai to improve productivity to near the 75% attainable yield. In conclusion, the high yield responses to fertilizer application provide opportunities to close the large yield gaps through balanced nutrition.
Mythic Paradigms and the Platonic Life: Becoming a Bacchus in Damascius’ Philosophical History
Authors: Miles Graeme
Published: November 2018

The fragmentary biographical work by Damascius, known as either the Life of Isidore or Philosophical History, appears to have begun with the myths of the dismemberment of Osiris and Dionysus. These programmatic allusions establish an important theme in the text that followed: ‘becoming a Bacchus’. This, as is clear from Damascius’ Phaedo Commentary, refers to the process of unifying and liberating oneself from the body at the ‘cathartic’ stage in the Neoplatonic scale of virtues. The acquisition of likeness to this specific deity is, therefore, a vital though far from final stage in the progression towards the ultimate goal of late antique Platonic philosophy: ‘becoming like god as far as possible’.
Trumpism, Citizenship, and the Future of the LGBTQ Movement
Authors: Murib Zein
Published: November 2018

Scholarship on lesbian, gay, bisexual, transgender, and queer (LGBTQ) politics argues that political claims, such as access to the military and marriage, are most effective when representatives from the group articulate that the desire for inclusion and participation in those institutions is similar to the desires held by their straight and nontransgender counterparts. This strategy of assimilation has yielded many positive legal changes. And yet the Donald Trump administration marks a period in which these gains have been repeatedly challenged and particular segments of the LGBTQ group are increasingly under attack. This article offers a preliminary analysis of how LGBTQ politics has been impacted by the 2016 election. Using a historical case study of LGBTQ identity construction and agenda development during the second half of the 1990s, I ask: how might the LGBTQ group mine its recent history for clues to rethink its political agenda and political strategies? Having shown that opportunities to advance a different movement—one focused on more radical, broadly inclusive changes—were bypassed during this period, I conclude by putting forward several recommendations for contemporary LGBTQ movement building and resistance strategies.
Präeklampsie: neue Definitionen
Authors: Schäffer Leonhard
Published: November 2018

Zusammenfassung. Die Präeklampsie ist eine Multisystemerkrankung, die vorwiegend zu einer systemischen Beeinträchtigung der mütterlichen Endothelfunktion führt. Eine Dysbalance von proangiogenen und antiangiogenen Faktoren ist dabei massgeblich beteiligt. Die vaskuläre Erkrankung führt zur klinischen Manifestation der Symptome wie arterieller Hypertonie und zur Beteiligung der Endorgane, v.a. Niere, Leber und Gehirn. Das klassische Diagnosekriterium «Proteinurie» ist gemäss internationaler Empfehlungen nicht mehr obligat zur Diagnosestellung erforderlich, sondern nur noch ein mögliches Kriterium und kann durch die Kriterien mütterliche Organbeteiligung oder fetale Wachstumsretardierung ersetzt werden. Die Weisskittelhypertonie wird in die Klassifikation der hypertensiven Erkrankungen zusätzlich aufgenommen. Die Begrifflichkeit «leichte» Präeklampsie wird im klinischen Setting wegen der potenziell raschen Verschlechterung und damit einhergehenden mütterlichen und fetalen Gefährdung nicht empfohlen.
Doherty Receives 2018 Space Physics and Aeronomy Richard Carrington Education and Public Outreach (SPARC) Award
Authors:   AGU
Published: November 2018

Patricia Doherty will receive the 2018 Space Physics and Aeronomy Richard Carrington Education and Public Outreach (SPARC) Award at AGU’s Fall Meeting 2018, to be held 10–14 December in Washington, D.�C. The award is given “for significant and outstanding impact on students’ and the public’s understanding of our science through their education and/or outreach activities.”
Tool to Capture Marine Biological Activity Gets Coastal Upgrade
Authors: Stanley Sarah
Published: November 2018

Upwelling hinders an efficient method to estimate a key measure of biological productivity in coastal waters, but accounting for surface temperatures could boost accuracy.
Simulated Global Climate Response to Tropospheric Ozone‐Induced Changes in Plant Transpiration
Authors: Arnold S. R. , Lombardozzi D. , Lamarque J.‐F. , Richardson T. , Emmons L. K. , Tilmes S. , Sitch S. A. , Folberth G. , Hollaway M. J. , Val Martin M.
Published: November 2018

Tropospheric ozone (O3) pollution is known to damage vegetation, reducing photosynthesis and stomatal conductance, resulting in modified plant transpiration to the atmosphere. We use an Earth system model to show that global transpiration response to near‐present‐day surface tropospheric ozone results in large‐scale global perturbations to net outgoing long‐wave and incoming shortwave radiation. Our results suggest that the radiative effect is dominated by a reduction in shortwave cloud forcing in polluted regions, in response to ozone‐induced reduction in land‐atmosphere moisture flux and atmospheric humidity. We simulate a statistically significant response of annual surface air temperature of up to ~ +1.5 K due to this ozone effect in vegetated regions subjected to ozone pollution. This mechanism is expected to further increase the net warming resulting from historic and future increases in tropospheric ozone.
Large‐Scale Ducting of Pc1 Pulsations Observed by Swarm Satellites and Multiple Ground Networks
Authors: Kim Hyangpyo , Hwang Junga , Park Jaeheung , Miyashita Yukinaga , Shiokawa Kazuo , Mann Ian R. , Raita Tero , Lee Jaejin
Published: November 2018

Low Earth orbit satellites frequently encounter Pc1 pulsations, but most have been observed with limited latitudinal extent or short lifetime. In this study we analyze two large‐scale Pc1 pulsations (both latitudinally wide and long‐lasting) generated by ionospheric ducting effect using Swarm and ground magnetometers on 25 June and 3 September 2015. Swarm observed the 25 June pulsations on both dayside and nightside during the storm time substorm (a strong geomagnetic storm on 23 June withDst =  − 204 nT). We found the Pc1 pulsations were pervasive in both magnetic local time sectors of dayside and nightside for at least 2 hr. Another large Pc1 pulsation on 3 September was observed during a nonstorm substorm period. We conclude that (1) ionospheric ducting can transmit Pc1 waves to a wide range of L shells, (2) geomagnetic storm is not a prerequisite for such large‐scale ducting, and (3) wave intensity can abruptly decrease across sharp gradients in the ionospheric plasma density.
Azimuthal Seismic Anisotropy in the Upper Crust of the Japanese Islands Induced by the 2011 Tohoku‐Oki Megathrust Earthquake
Authors: Kim Ilgoo , Hong Tae‐Kyung
Published: November 2018

We investigatedVP/VSchanges in the upper crust of the Japanese islands after the 2011MW9.0 Tohoku‐Oki megathrust earthquake. AbruptVP/VSchanges with azimuth‐dependent variations were observed after the megathrust earthquake. TheVP/VSchanges ranged between −0.0458 (±0.0012) and 0.0422 (±0.0033). Large localizedVP/VSchanges over regional distances suggested medium‐dependent deformation. PeakVP/VSchanges were observed along paths subparallel or subperpendicular to the directions toward the megathrust earthquake. TheVP/VSchanges displayed characteristic 2θvariations as a function of the azimuth difference, suggesting azimuthal seismic anisotropy. TheVP/VSratio recovered gradually over time. Some regions presented permanentVP/VSchanges. The azimuthal seismic anisotropy may have developed from preferential crack orientation as a consequence of the combined effects of lithospheric displacements and a depth‐dependent ambient stress field. It appears that recovery of the medium properties may take decades.
Influence of Clay, Calcareous Microfossils, and Organic Matter on the Nature and Diagenetic Evolution of Pore Systems in Mudstones
Authors: Mathia Eliza J. , Rexer Thomas F. T. , Thomas K. Mark , Bowen Leon , Aplin Andrew C.
Published: November 2018

Mudstones exert a fundamental control on the flow of both aqueous and nonaqueous fluids in sedimentary basins. Predicting their flow and storage properties requires an understanding of pore size and connectivity, yet there are very few quantitative descriptions of pore systems of mineralogically and texturally well‐characterized mudstones. We use a combination of electron microscopy, mercury injection capillary pressure porosimetry, and CO2 sorption methods to generate a quantitative description of the size distribution, connectivity, and evolution of pore systems in a sequence of Posidonia Shale mudstones buried to 100–180 °C. We place the pore data into a detailed mineralogical, petrographical, and textural context to show that the nature and evolution of porosity and pore systems can be described in terms of associations with clay‐rich, microfossil‐rich, and organic matter‐rich domains, common to many mudstones. Pore size distributions are described by power laws, and pore systems are well connected across the full nanometer‐micrometer spectrum of pore sizes. However, connected networks occur primarily through pores <10 nm radius, with typically 20–40% of total porosity associated with pores with radii < ~3 nm, within both organic matter and the clay matrix. Clay‐rich, microfossil‐rich, and organic matter‐rich domains have distinct pore size distributions which evolve in very different ways with increasing thermal maturity. We suggest that the flow of aqueous and nonaqueous fluids depends not only on the overall connectivity of pores but also the larger‐scale connectivity and wetting state of clay‐rich, microfossil‐rich, and organic matter‐rich domains.
An Extended Grain‐Based Model Accounting for Microstructures in Rock Deformation
Authors: Zhang Yahui , Wong Louis Ngai Yuen , Chan Ka Kit
Published: November 2018

Reliable prediction of the rock fracturing process is a challenging issue in exploitation of deep earth resources in which artificial creation of complex fracture networks is employed. The grain‐based modeling (GBM) approach is a promising numerical technique for its unique capability to simulate the fracturing behavior of crystalline rocks. An extended grain‐based model is developed to improve the traditional Voronoi GBM from two aspects. First, digital image processing technique is presented to incorporate actual rock microstructures into the numerical model. Second, the effect of initial microcracks is considered by integrating a statistical discrete fracture network model into GBM. By simulating semicircular bending tests on 16 extended GBMs and 3 Voronoi GBMs, the effects of rock microstructures and initial microcracks on microcracking behavior and mechanical properties are analyzed. Cracking patterns are classified into four types for the first time with respect to fracture toughness and crack initiation threshold. The results indicate that the use of a statistical structure or a purely deterministic GBM without consideration of initial microcracks cannot realistically describe grain‐scale discontinuities, which likely leads to biased evaluations of the rock failure process.
Matrix Approach of Seismic Imaging: Application to the Erebus Volcano, Antarctica
Authors: Blondel Thibaud , Chaput Julien , Derode Arnaud , Campillo Michel , Aubry Alexandre
Published: November 2018

Multiple scattering of seismic waves is often seen as a nightmare for conventional migration techniques that generally rely on a ballistic or a single‐scattering assumption. In heterogeneous areas such as volcanoes, the multiple‐scattering contribution limits the imaging‐depth to one scattering mean free path, the mean distance between two successive scattering events for body waves. In this Letter, we propose a matrix approach of passive seismic imaging that pushes back this fundamental limit by making an efficient use of scattered body waves drowned into a noisy seismic coda. As a proof of concept, the case of the Erebus volcano in Antarctica is considered. The Green's functions between a set of geophones placed on top of the volcano are first retrieved by the cross correlation of coda waves induced by multiple icequakes. This set of impulse responses forms a reflection matrix. By combining a matrix discrimination of singly scattered waves with iterative time reversal, we are able to push back the multiple scattering limit beyond 10 scattering mean free paths. The matrix approach reveals the internal structure of the Erebus volcano: A chimney‐shaped structure at shallow depths, a magma reservoir at 2,500 m and several cavities at sea level and below it. The matrix approach paves the way toward a greatly improved monitoring of volcanic structures at depth. Beyond this specific case, the matrix approach of seismic imaging can generally be applied to all scales and areas where multiple scattering events undergone by body waves prevent in‐depth imaging of the Earth's crust.
The ERK and JNK pathways in the regulation of metabolic reprogramming
Authors: Papa Salvatore , Choy Pui Man , Bubici Concetta
Published: November 2018

Most tumor cells reprogram their glucose metabolism as a result of mutations in oncogenes and tumor suppressors, leading to the constitutive activation of signaling pathways involved in cell growth. This metabolic reprogramming, known as aerobic glycolysis or the Warburg effect, allows tumor cells to sustain their fast proliferation and evade apoptosis. Interfering with oncogenic signaling pathways that regulate the Warburg effect in cancer cells has therefore become an attractive anticancer strategy. However, evidence for the occurrence of the Warburg effect in physiological processes has also been documented. As such, close consideration of which signaling pathways are beneficial targets and the effect of their inhibition on physiological processes are essential. The MAPK/ERK and MAPK/JNK pathways, crucial for normal cellular responses to extracellular stimuli, have recently emerged as key regulators of the Warburg effect during tumorigenesis and normal cellular functions. In this review, we summarize our current understanding of the roles of the ERK and JNK pathways in controlling the Warburg effect in cancer and discuss their implication in controlling this metabolic reprogramming in physiological processes and opportunities for targeting their downstream effectors for therapeutic purposes.
Adaptive particle representation of fluorescence microscopy images
Authors: Cheeseman Bevan L. , Günther Ulrik , Gonciarz Krzysztof , Susik Mateusz , Sbalzarini Ivo F.
Published: November 2018

Modern microscopes create a data deluge with gigabytes of data generated each second, and terabytes per day. Storing and processing this data is a severe bottleneck, not fully alleviated by data compression. We argue that this is because images are processed as grids of pixels. To address this, we propose a content-adaptive representation of fluorescence microscopy images, the Adaptive Particle Representation (APR). The APR replaces pixels with particles positioned according to image content. The APR overcomes storage bottlenecks, as data compression does, but additionally overcomes memory and processing bottlenecks. Using noisy 3D images, we show that the APR adaptively represents the content of an image while maintaining image quality and that it enables orders of magnitude benefits across a range of image processing tasks. The APR provides a simple and efficient content-aware representation of fluosrescence microscopy images.
Stress-induced formation of cell wall-deficient cells in filamentous actinomycetes
Authors: Ramijan Karina , Ultee Eveline , Willemse Joost , Zhang Zheren , Wondergem Joeri A. J. , van der Meij Anne , Heinrich Doris , Briegel Ariane , van Wezel Gilles P. , Claessen Dennis
Published: November 2018

The cell wall is a shape-defining structure that envelopes almost all bacteria and protects them from environmental stresses. Bacteria can be forced to grow without a cell wall under certain conditions that interfere with cell wall synthesis, but the relevance of these wall-less cells (known as L-forms) is unclear. Here, we show that several species of filamentous actinomycetes have a natural ability to generate wall-deficient cells in response to hyperosmotic stress, which we call S-cells. This wall-deficient state is transient, as S-cells are able to switch to the normal mycelial mode of growth. However, prolonged exposure of S-cells to hyperosmotic stress yields variants that are able to proliferate indefinitely without their cell wall, similarly to L-forms. We propose that formation of wall-deficient cells in actinomycetes may serve as an adaptation to osmotic stress.
Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing
Authors: Bartoschek Michael , Oskolkov Nikolay , Bocci Matteo , Lövrot John , Larsson Christer , Sommarin Mikael , Madsen Chris D. , Lindgren David , Pekar Gyula , Karlsson Göran , Ringnér Markus , Bergh Jonas , Björklund Åsa , Pietras Kristian
Published: November 2018

Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment, although their origin and roles in shaping disease initiation, progression and treatment response remain unclear due to significant heterogeneity. Here, following a negative selection strategy combined with single-cell RNA sequencing of 768 transcriptomes of mesenchymal cells from a genetically engineered mouse model of breast cancer, we define three distinct subpopulations of CAFs. Validation at the transcriptional and protein level in several experimental models of cancer and human tumors reveal spatial separation of the CAF subclasses attributable to different origins, including the peri-vascular niche, the mammary fat pad and the transformed epithelium. Gene profiles for each CAF subtype correlate to distinctive functional programs and hold independent prognostic capability in clinical cohorts by association to metastatic disease. In conclusion, the improved resolution of the widely defined CAF population opens the possibility for biomarker-driven development of drugs for precision targeting of CAFs.
The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background
Authors: Zhu Lei , Tripathi Jaishree , Rocamora Frances Maureen , Miotto Olivo , van der Pluijm Rob , Voss Till S. , Mok Sachel , Kwiatkowski Dominic P. , Nosten François , Day Nicholas P. J. , White Nicholas J. , Dondorp Arjen M. , Bozdech Zbynek ,   Tracking Resistance to Artemisinin Collaboration I, Phyo Aung Pyae , Ashley Elizabeth A. , Smithuis Frank , Lin Khin , Tun Kyaw Myo , Faiz M Abul , Mayxay Mayfong , Dhorda Mehul , Thuy-Nhien Nguyen Thanh , Newton Paul N. , Pukrittayakamee Sasithon , Hlaing Tin M. , Hien Tran Tinh , Htut Ye
Published: November 2018

The predisposition of parasites acquiring artemisinin resistance still remains unclear beyond the mutations in Pfk13 gene and modulation of the unfolded protein response pathway. To explore the chain of casualty underlying artemisinin resistance, we reanalyze 773 P. falciparum isolates from TRACI-study integrating TWAS, GWAS, and eQTL analyses. We find the majority of P. falciparum parasites are transcriptomically converged within each geographic site with two broader physiological profiles across the Greater Mekong Subregion (GMS). We report 8720 SNP-expression linkages in the eastern GMS parasites and 4537 in the western. The minimal overlap between them suggests differential gene regulatory networks facilitating parasite adaptations to their unique host environments. Finally, we identify two genetic and physiological backgrounds associating with artemisinin resistance in the GMS, together with a farnesyltransferase protein and a thioredoxin-like protein which may act as vital intermediators linking the Pfk13 C580Y mutation to the prolonged parasite clearance time.
Transcriptomic landscape of the blastema niche in regenerating adult axolotl limbs at single-cell resolution
Authors: Leigh Nicholas D. , Dunlap Garrett S. , Johnson Kimberly , Mariano Rachelle , Oshiro Rachel , Wong Alan Y. , Bryant Donald M. , Miller Bess M. , Ratner Alex , Chen Andy , Ye William W. , Haas Brian J. , Whited Jessica L.
Published: November 2018

Regeneration of complex multi-tissue structures, such as limbs, requires the coordinated effort of multiple cell types. In axolotl limb regeneration, the wound epidermis and blastema have been extensively studied via histology, grafting, and bulk-tissue RNA-sequencing. However, defining the contributions of these tissues is hindered due to limited information regarding the molecular identity of the cell types in regenerating limbs. Here we report unbiased single-cell RNA-sequencing on over 25,000 cells from axolotl limbs and identify a plethora of cellular diversity within epidermal, mesenchymal, and hematopoietic lineages in homeostatic and regenerating limbs. We identify regeneration-induced genes, develop putative trajectories for blastema cell differentiation, and propose the molecular identity of fibroblast-like blastema progenitor cells. This work will enable application of molecular techniques to assess the contribution of these populations to limb regeneration. Overall, these data allow for establishment of a putative framework for adult axolotl limb regeneration.
Aqueous thermogalvanic cells with a high Seebeck coefficient for low-grade heat harvest
Authors: Duan Jiangjiang , Feng Guang , Yu Boyang , Li Jia , Chen Ming , Yang Peihua , Feng Jiamao , Liu Kang , Zhou Jun
Published: November 2018

Thermogalvanic cells offer a cheap, flexible and scalable route for directly converting heat into electricity. However, achieving a high output voltage and power performance simultaneously from low-grade thermal energy remains challenging. Here, we introduce strong chaotropic cations (guanidinium) and highly soluble amide derivatives (urea) into aqueous ferri/ferrocyanide ([Fe(CN)6]4−/[Fe(CN)6]3−) electrolytes to significantly boost their thermopowers. The corresponding Seebeck coefficient and temperature-insensitive power density simultaneously increase from 1.4 to 4.2 mV K−1 and from 0.4 to 1.1 mW K−2 m−2, respectively. The results reveal that guanidinium and urea synergistically enlarge the entropy difference of the redox couple and significantly increase the Seebeck effect. As a demonstration, we design a prototype module that generates a high open-circuit voltage of 3.4 V at a small temperature difference of 18 K. This thermogalvanic cell system, which features high Seebeck coefficient and low cost, holds promise for the efficient harvest of low-grade thermal energy.
Single-cell mutation identification via phylogenetic inference
Authors: Singer Jochen , Kuipers Jack , Jahn Katharina , Beerenwinkel Niko
Published: November 2018

Reconstructing the evolution of tumors is a key aspect towards the identification of appropriate cancer therapies. The task is challenging because tumors evolve as heterogeneous cell populations. Single-cell sequencing holds the promise of resolving the heterogeneity of tumors; however, it has its own challenges including elevated error rates, allelic drop-out, and uneven coverage. Here, we develop a new approach to mutation detection in individual tumor cells by leveraging the evolutionary relationship among cells. Our method, called SCIΦ, jointly calls mutations in individual cells and estimates the tumor phylogeny among these cells. Employing a Markov Chain Monte Carlo scheme enables us to reliably call mutations in each single cell even in experiments with high drop-out rates and missing data. We show that SCIΦ outperforms existing methods on simulated data and applied it to different real-world datasets, namely a whole exome breast cancer as well as a panel acute lymphoblastic leukemia dataset.
Genome wide association analysis in a mouse advanced intercross line
Authors: Gonzales Natalia M. , Seo Jungkyun , Hernandez Cordero Ana I. , St. Pierre Celine L. , Gregory Jennifer S. , Distler Margaret G. , Abney Mark , Canzar Stefan , Lionikas Arimantas , Palmer Abraham A.
Published: November 2018

The LG/J x SM/J advanced intercross line of mice (LG x SM AIL) is a multigenerational outbred population. High minor allele frequencies, a simple genetic background, and the fully sequenced LG and SM genomes make it a powerful population for genome-wide association studies. Here we use 1,063 AIL mice to identify 126 significant associations for 50 traits relevant to human health and disease. We also identify thousands of cis- and trans-eQTLs in the hippocampus, striatum, and prefrontal cortex of ~200 mice. We replicate an association between locomotor activity and Csmd1, which we identified in an earlier generation of this AIL, and show that Csmd1 mutant mice recapitulate the locomotor phenotype. Our results demonstrate the utility of the LG x SM AIL as a mapping population, identify numerous novel associations, and shed light on the genetic architecture of mammalian behavior.
Unifying host-associated diversification processes using butterfly–plant networks
Authors: Braga Mariana P. , Guimarães Paulo R. , Wheat Christopher W. , Nylin Sören , Janz Niklas
Published: November 2018

Explaining the exceptional diversity of herbivorous insects is an old problem in evolutionary ecology. Here we focus on the two prominent hypothesised drivers of their diversification, radiations after major host switch or variability in host use due to continuous probing of new hosts. Unfortunately, current methods cannot distinguish between these hypotheses, causing controversy in the literature. Here we present an approach combining network and phylogenetic analyses, which directly quantifies support for these opposing hypotheses. After demonstrating that each hypothesis produces divergent network structures, we then investigate the contribution of each to diversification in two butterfly families: Pieridae and Nymphalidae. Overall, we find that variability in host use is essential for butterfly diversification, while radiations following colonisation of a new host are rare but can produce high diversity. Beyond providing an important reconciliation of alternative hypotheses for butterfly diversification, our approach has potential to test many other hypotheses in evolutionary biology.
The proton and metal binding sites responsible for the pH-dependent green-red bioluminescence color tuning in firefly luciferases
Authors: Viviani Vadim R. , Gabriel Gabriele V. M. , Bevilaqua Vanessa R. , Simões A. F. , Hirano T. , Lopes-de-Oliveira P. S.
Published: November 2018

Firefly luciferases produce yellow-green light under physiological and alkaline conditions, however at acidic pH, higher temperatures or in the presence of heavy metals the color changes to red, a property called pH-sensitivity. Despite many decades of studies, the proton and metal binding sites responsible for pH-sensitivity remain enigmatic. Previously we suggested that the salt bridge E311/R337 keeps a closed conformation of the luciferin phenolate binding site. Here we further investigated the effect of this salt bridge and mutations of the neighbor residues H310 and E/N354, on metal and pH-sensitivity of firefly luciferases emitting distinct bioluminescence colors (Cratomorphus distinctus: 548 nm;Macrolampissp2: 569 nm). The substitutions of H310 and E/N354 modulate metal sensitivity, whereas the carboxylate of E311 may work as the catalytic base essential for green bioluminescence and pH-sensitivity. Modeling studies showed that H310, E311 and E354 side-chains coordinate Zinc, constituting the metal binding site and the pH-sensor. Electrostatic potential and pKa calculations suggest that the external couple H310/E354 is affected by pH, whereas E311/R337 make a stabilized internal pair which retains excited oxyluciferin ejected proton near its phenolate group into a high energy state, promoting yellow-green bioluminescence. Protonation or metal binding weaken these electrostatic gates and their ability to retain the excited oxyluciferin released proton near its phenolate, promoting red light emission.
Reconstructing the evolutionary history of F420-dependent dehydrogenases
Authors: Mascotti M. Laura , Kumar Hemant , Nguyen Quoc-Thai , Ayub Maximiliano Juri , Fraaije Marco W.
Published: November 2018

During the last decade the number of characterized F420-dependent enzymes has significantly increased. Many of these deazaflavoproteins share a TIM-barrel fold and are structurally related to FMN-dependent luciferases and monooxygenases. In this work, we traced the origin and evolutionary history of the F420-dependent enzymes within the luciferase-like superfamily. By a thorough phylogenetic analysis we inferred that the F420-dependent enzymes emerged from a FMN-dependent common ancestor. Furthermore, the data show that during evolution, the family of deazaflavoproteins split into two well-defined groups of enzymes: the F420-dependent dehydrogenases and the F420-dependent reductases. By such event, the dehydrogenases specialized in generating the reduced deazaflavin cofactor, while the reductases employ the reduced F420 for catalysis. Particularly, we focused on investigating the dehydrogenase subfamily and demonstrated that this group diversified into three types of dehydrogenases: the already known F420-dependent glucose-6-phosphate dehydrogenases, the F420-dependent alcohol dehydrogenases, and the sugar-6-phosphate dehydrogenases that were identified in this study. By reconstructing and experimentally characterizing ancestral and extant representatives of F420-dependent dehydrogenases, their biochemical properties were investigated and compared. We propose an evolutionary path for the emergence and diversification of the TIM-barrel fold F420-dependent dehydrogenases subfamily.
Antimicrobial resistance prediction and phylogenetic analysis of Neisseria gonorrhoeae isolates using the Oxford Nanopore MinION sequencer
Authors: Golparian Daniel , Donà Valentina , Sánchez-Busó Leonor , Foerster Sunniva , Harris Simon , Endimiani Andrea , Low Nicola , Unemo Magnus
Published: November 2018

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is common, compromising gonorrhoea treatment internationally. Rapid characterisation of AMR strains could ensure appropriate and personalised treatment, and support identification and investigation of gonorrhoea outbreaks in nearly real-time. Whole-genome sequencing is ideal for investigation of emergence and dissemination of AMR determinants, predicting AMR, in the gonococcal population and spread of AMR strains in the human population. The novel, rapid and revolutionary long-read sequencer MinION is a small hand-held device that generates bacterial genomes within one day. However, accuracy of MinION reads has been suboptimal for many objectives and the MinION has not been evaluated for gonococci. In this first MinION study for gonococci, we show that MinION-derived sequences analysed with existing open-access, web-based sequence analysis tools are not sufficiently accurate to identify key gonococcal AMR determinants. Nevertheless, using an in house-developed CLC Genomics Workbench including de novo assembly and optimised BLAST algorithms, we show that 2D ONT-derived sequences can be used for accurate prediction of decreased susceptibility or resistance to recommended antimicrobials in gonococcal isolates. We also show that the 2D ONT-derived sequences are useful for rapid phylogenomic-based molecular epidemiological investigations, and, in hybrid assemblies with Illumina sequences, for producing contiguous assemblies and finished reference genomes.
Facial expression as a potential measure of both intent and emotion
Authors: Camerlink Irene , Coulange Estelle , Farish Marianne , Baxter Emma M. , Turner Simon P.
Published: November 2018

Facial expressions convey information on emotion, physical sensations, and intent. The much debated theories that facial expressions can be emotions or signals of intent have largely remained separated in animal studies. Here we integrate these approaches with the aim to 1) investigate whether pigs may use facial expressions as a signal of intent and; 2) quantify differences in facial metrics between different contexts of potentially negative emotional state. Facial metrics of 38 pigs were recorded prior to aggression, during aggression and during retreat from being attacked in a dyadic contest. Ear angle, snout ratio (length/height) and eye ratio from 572 images were measured. Prior to the occurrence of aggression, eventual initiators of the first bite had a smaller snout ratio and eventual winners showed a non-significant tendency to have their ears forward more than eventual losers. During aggression, pigs’ ears were more forward orientated and their snout ratio was smaller. During retreat, pigs’ ears were backwards and their eyes open less. The results suggest that facial expressions can communicate aggressive intent related to fight success, and that facial metrics can convey information about emotional responses to contexts involving aggression and fear.
Seasonal Deposition and Lifting of Dust on Mars as Observed by the Curiosity Rover
Authors: Vicente-Retortillo Á. , Martínez G. M. , Renno N. , Newman C. E. , Ordonez-Etxeberria I. , Lemmon M. T. , Richardson M. I. , Hueso R. , Sánchez-Lavega A.
Published: November 2018

In situ measurements by the Curiosity rover provide a unique opportunity for studying the effects of dust on assets placed at the surface of Mars. Here we use in situ measurements of solar UV radiation to quantify the seasonal and interannual variability of dust accumulation on the sensor on the rover deck. We show that the amount of dust accumulated on the sensor follows a seasonal cycle, with net dust removal during the perihelion season until Ls ~ 300°, and net dust deposition until the end of the aphelion season (Ls ~ 300°–180°). We use independent in situ measurements of atmospheric opacity and pressure perturbations in combination with numerical modeling, showing that daytime convective vortices and nighttime winds are likely responsible for the seasonal dust cleaning, with the role of nighttime wind being more important in Martian Year (MY) 32 than in MY 33 and that of daytime convective vortices being more important in MY 33 than in MY 32. The fact that the UV sensor is cleaner in MY 33 than in MY 32 indicates that natural cleaning events make solar energy an excellent candidate to power extended (multiannual) Mars missions at similar latitudes as the Curiosity rover.