bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient production of glutathione with multi-pathway engineering in Corynebacterium glutamicum
Authors: Liu Wei , Zhu Xiangcheng , Lian Jiazhang , Huang Lei , Xu Zhinan
Published: August 2019

Glutathione is a bioactive tripeptide composed of glycine, l-cysteine, and l-glutamate, and has been widely used in pharmaceutical, food, and healthy products. The current metabolic studies of glutathione were mainly focused on the native producing strains with precursor amino acid supplementation. In the present work, Corynebacterium glutamicum, a workhorse for industrial production of a series of amino acids, was engineered to produce glutathione. First, the introduction of glutathione synthetase gene gshF from Streptococcus agalactiae fulfilled the ability of glutathione production in C. glutamicum and revealed that l-cysteine was the limiting factor. Then, considering the inherent capability of l-glutamate synthesis and the availability of external addition of low-cost glycine, l-cysteine biosynthesis was enhanced using a varieties of pathway engineering methods, such as disrupting the degradation pathways of l-cysteine and l-serine, and removing the repressor responsible for sulfur metabolism. Finally, the simultaneously introduction of gshF and enhancement of cysteine formation enabled C. glutamicum strain to produce glutathione greatly. Without external addition of l-cysteine and l-glutamate, 756 mg/L glutathione was produced. This is first time to demonstrate the potential of the glutathione non-producing strain C. glutamicum for glutathione production and provide a novel strategy to construct glutathione-producing strains.
A treatment approach for couples with disrupted sperm DNA integrity and recurrent ART failure
Authors: Parrella Alessandra , Keating Derek , Cheung Stephanie , Xie Philip , Stewart Joshua D. , Rosenwaks Zev , Palermo Gianpiero D.
Published: August 2019

Objective

To test a novel method to select spermatozoa with high chromatin integrity.

Design

Specimens with high sperm chromatin fragmentation (SCF) were selected by density gradient selection (DGS) and microfluidic sperm sorting (MSS).

Setting

Academic medical center.

Patient(s)

Ejaculates from consenting men were processed by DGS/MSS. Couples underwent ICSI cycles with spermatozoa processed by DGS/MSS. Clinical outcomes were evaluated after embryo transfer.

Intervention(s)

SCF was measured by TUNEL. ICSI with spermatozoa selected by DGS and MSS was performed.

Main outcome measure(s)

Fertilization, embryo implantation, and pregnancy outcomes were compared between DGS and MSS.

Result(s)

A total of 23 men had an average SCF of 20.7 ± 10%. After DGS and MSS, the SCF was 12.5 ± 5% and 1.8 ± 1%, respectively. In couples who underwent ICSI, the average SCF was 28.8 ± 9%, which fell to 21.0 ± 9% after DGS and 1.3 ± 0.7% after MSS. Four couples underwent 11 ICSI cycles with DGS and achieved one (25%) pregnancy that resulted in pregnancy loss. In four subsequent ICSI cycles with MSS, an ongoing clinical pregnancy rate of 50% was achieved. Five additional couples underwent 12 cycles of ICSI with DGS. After preimplantation genetic testing for aneuploidy, 30.3% of the embryos were euploid. One pregnancy was achieved, resulting in pregnancy loss. With MSS, 31.5% of the embryos were euploid and 4 couples obtained a pregnancy. Finally, sixteen couples underwent 20 ICSI cycles solely with MSS at our center. Of these couples, 8 had failed 13 ICSI cycles with DGS elsewhere. These couples achieved an overall implantation of 34.5% (10/29) and a pregnancy rate of 58.8% (10/17).

Conclusion(s)

Microfluidic selection yielded spermatozoa with optimal genomic integrity and improved chances of obtaining a euploid conceptus.
Guidance for Autonomous Aerial Manipulator Using Stereo Vision
Authors: Kanellakis Christoforos , Nikolakopoulos George
Published: August 2019

Combining the agility of Micro Aerial Vehicles (MAV) with the dexterity of robotic arms leads to a new era of Aerial Robotic Workers (ARW) targeting infrastructure inspection and maintenance tasks. Towards this vision, this work focuses on the autonomous guidance of the aerial end-effector to either reach or keep desired distance from areas/objects of interest. The proposed system: 1) is structured around a real-time object tracker, 2) employs stereo depth perception to extract the target location within the surrounding scene, and finally 3) generates feasible poses for both the arm and the MAV relative to the target. The performance of the proposed scheme is experimentally demonstrated in multiple scenarios of increasing complexity.
Syngas for biorefineries from thermochemical gasification of lignocellulosic fuels and residues—5 years’ experience with an advanced dual fluidized bed gasifier design
Authors: Schmid Johannes Christian , Benedikt Florian , Fuchs Josef , Mauerhofer Anna Magdalena , Müller Stefan , Hofbauer Hermann
Published: August 2019

In many processes proposed for biorefineries, recycling procedures, and industrial or agricultural production processes, residue is generated which could be further transformed by thermochemical conversion via gasification. The technology of dual fluidized bed steam gasification is capable of producing a valuable product gas out of such residue. The generated nitrogen-free product gas can be used for heat and power production and is suitable for separating gases (e.g. hydrogen). However, if the product gas is cleaned, its use as syngas is more beneficial for manufacturing renewable chemical substances, like synthetic natural gas, methanol, Fischer–Tropsch liquids, or mixed alcohols. This paper presents the results of experimental research from gasification test runs of different biogenic fuels, carried out with an advanced 100 kW pilot plant over the last 5 years at TU Wien. The focus is to provide an overview of measured results validated by mass and energy balances and to present key calculated performance indicating key figures of the test runs. In this way, the influence of various operational parameters and the composition of the product gas are evaluated. The presented results form the basis for the proper design of suitable gas-cleaning equipment. Subsequently, the clean syngas is available for several synthesis applications in future biorefineries.
Family Systems and Parents’ Financial Support for Education in Early Adulthood
Authors: Fomby Paula , Kravitz-Wirtz Nicole
Published: August 2019

Young adults raised outside of two-parent families receive less financial support from their families for education compared with peers who always lived with both parents. We consider how parents’ union status over time shapes contributions for young adult children’s education. Our approach emphasizes the dynamic relationship between family structure and family economic resources. Marginal structural models with inverse probability weights estimate the association of parents’ union status history with eventual financial transfers while not overcontrolling for the effects of union status operating indirectly through time-varying characteristics, such as coresident family composition and economic circumstances. The analytic sample includes parents of a recent cohort of young adults (Panel Study of Income Dynamics, 1983–2013, N = 2,754). Compared with parents who lived continuously with a child’s other parent, unpartnered parents’ transfers to children were 44 % to 90 % smaller, and repartnered parents’ transfers were one- to two-thirds smaller, depending on how long the parent was unpartnered or repartnered. Through its influence on subsequent coresident family composition and family economic resources, parents’ union status has indirect as well as direct associations with financial transfers to adult children for education.
FFKM sanitary seals enable process plants and manufacturing facilities to operate safely and efficiently
Authors: Atkinson Simon
Published: August 2019

Dichtomatik Ltd – the authorised UK distributor of the DuPont™ Kalrez® perfluoroelastomer (FFKM) range of materials – is offering new seals that enable process plants and manufacturing facilities to operate safely on a day-to-day basis, whilst improving productivity and process optimisation. This brief focus article highlights the benefits of using these seals which, claims the company, excel in applications involving foodstuffs and pharmaceuticals.
Precision Polymer Engineering's sealing material plays a key role in Venice's flood prevention measures
Authors: Atkinson Simon
Published: August 2019

A sealing material developed by Precision Polymer Engineering Ltd (PPE) of Blackburn, UK, is playing a key role in flood prevention measures off the coast of Italy. This focus article provides a glimpse into how technology from the company – which designs, develops and manufactures high-performance moulded rubber seals, rubber gaskets and elastomer components for industries around the world – is being used in a series of massive flood gates that has been installed to protect the city of Venice and the Venetian Lagoon from flooding.
The Tragedy of King Lear
Authors: Shakespeare William
Published: August 2019

The New Cambridge Shakespeare appeals to students worldwide for its up-to-date scholarship and emphasis on performance. The series features line-by-line commentaries and textual notes on the plays and poems. Introductions are regularly refreshed with accounts of new critical, stage and screen interpretations. For this second edition of King Lear, Jay L. Halio has added a new introductory section that focuses on recent developments in scholarly criticism as well as on contemporary productions of the play. The edition features a comprehensive account of Shakespeare's sources, including literary, political and folkloric influences on the work. Halio's text is edited from the Folio and he explains the differences between the quarto and Folio versions, alerting the reader to the rival charms of the quarto by sampling parallel passages in the Introduction and by including in an Appendix annotated passages that are unique to the quarto. An updated reading list completes the edition.
The Third Part of King Henry VI
Authors: Shakespeare William
Published: August 2019

The New Cambridge Shakespeare appeals to students worldwide for its up-to-date scholarship and emphasis on performance. The series features line-by-line commentaries, textual notes on the plays and poems and an extensive Introduction. Shakespeare's plays about the reign of King Henry VI were written at the beginning of his career. A recent series of outstanding productions has demonstrated their theatrical vitality, and their sceptical questioning of Elizabethan orthodoxies has been understood through revisionist readings of the history of Shakespeare's own times. In The Third Part of King Henry VI, Shakespeare extends his essay on monarchical politics by contrasting two kings, the good but ineffective Henry VI with his rival, the sensual and victorious Edward IV. He also shows the perils of aristocratic factionalism in a series of scenes that display the grievous wounds caused by the Wars of the Roses.
Xenophobia’s Contours During an Ebola Epidemic: Proximity and the Targeting of Peul Migrants in Senegal
Authors: Onoma Ato Kwamena
Published: August 2019

This article examines the effect of geographical proximity on targeting patterns during Ebola-era xenophobic outbursts by Senegalese against a migrant Peul population of Guinean origins. It highlights the limited extent to which epidemics shape the micro-dynamics of outbreaks of xenophobia during public health crises, demonstrating that epidemics are not defining events that inflect inter-group relations. They mostly reinforce long-persisting patterns of exclusion. The conclusion is that the contours of xenophobia in contexts marked by public health crises and in those situations in which these issues of public health do not constitute a major concern tend to mirror each other.
Producing Monyul as Buffer: Spatial politics in a colonial frontier
Authors: GOHAIN SWARGAJYOTI
Published: August 2019

This article focuses on the Tawang and West Kameng districts of Arunachal Pradesh, northeast India, collectively known as Monyul. It was ruled by Tibet for three centuries before the 1914 McMahon Line boundary included it in India. Even after that, cross-border exchanges between Monyul and Tibet continued until the 1962 Sino-Indian war, following which border passages between the two were closed. Today, Monyul is a marginal region, geographically distant from centres of industry and education, and lacking in terms of infrastructure. This article traces Monyul's marginality not simply to the border war, but to spatial practices of the British colonial state, beginning with the mapping of the boundary in 1914. It shows how Monyul was constructed as a buffer, despite being within a delimited boundary, first, by excluding it from regular administration, and, secondly, by pushing back the older Tibetan administration, thereby, making it (what I call) a ‘zone of difference/indifference’. But the buffer project was subject to contestation, mostly from the Tibetan religious aristocracy, whose temporal hold over, and material interests in, Monyul were challenged by the latter's incorporation into colonial India.
The transformation of an urban political elite: oligarchy and aristocracy in sixteenth-century Ghent
Authors: Baguet Jelten
Published: August 2019

The composition of the political elites in sixteenth-century Ghent, one of the political and economic centres of the county of Flanders, changed from a relatively open elite group that included representatives from the craft guilds into a compact, aristocratic class. This article analyses the reasons for this transformation. First, the number of office-holders in the city council declined and power was increasingly concentrated in the hands of a smaller political elite because of interventions in the urban political framework by the Habsburg authorities in the wake of a fiscal rebellion (1537–40) and a Calvinist takeover of power (1578–84). Secondly, the once dominant position of the craft guilds on Ghent's two benches of aldermen was weakened by institutional reforms, a Catholic backlash against Calvinism and an economic recession. Thirdly, the growing wealth gap between rulers and the ruled, coupled with an influx of noblemen into Ghent City Council, gave urban politics a more aristocratic character. Consequently, a series of interconnected changes gave rise to a trend towards oligarchy and aristocracy on the city's benches of aldermen.
Peer Victimization, Coping Strategies, Depression, and Suicidal Ideation Among Young Adolescents
Authors: Cohen Or Ben Simon , Shahar Golan , Brunstein Klomek Anat
Published: August 2019

Abstract. Background: Victimization by bullying among adolescents is a widespread phenomenon associated with depression and suicidal ideation. Coping with bullying may include aggressive responding and self-blame. Aims: The purpose of this study was to examine the role adolescent self-blame and aggression – representing coping with peer bullying – in depression and suicide ideation. Method: We recruited 97 "pure" victims (41 girls; mean age = 12.69, SD = .80) identified from a sample of 505 adolescents (242 girls; mean age = 12.73, SD = .81) from two Israeli high schools. Self-report questionnaires were used to assess victimization, aggressive responses, self-blame, depression, and suicide ideation. Results: Self-blame in the face of peer bullying was uniquely associated with both depression and suicide ideation. The effect was robust even after controlling for level of victimization. No direct effect of aggressive coping or moderating effects of self-blame or aggression on the association between victimization and depression/suicide ideation were found. Limitations: This study used a cross-sectional design and made exclusive use of self-report measures. Conclusion: Adolescents who blame themselves for being bullied might be at a heightened risk for depression and suicidality compared to adolescents who did not use self-blame.
Societal Reactions to Suicide in Ghana
Authors: Andoh-Arthur Johnny , Knizek Birthe Loa , Osafo Joseph , Hjelmeland Heidi
Published: August 2019

Abstract. Background: Condemnatory reactions toward suicide are prevalent in Africa, yet no study has examined how society reacts to suicides from the perspective of suicide-bereaved persons. Aims: This qualitative study explored societal reactions to suicides so as to further our understanding of the problem in Ghana. Method: Using a semi-structured interview guide, we interviewed 45 close relations of 14 men who took their lives. Results: The reactions followed ontological questions of what suicide means (construing the act), its impact (consequences), why it happened and who to blame (attributions and allocation of responsibility), and how to remedy perceived damages (damage control). Limitations: Focusing on suicides of only men might have limited the range of societal reactions to suicide in general. Conclusion: Reparative and retributive societal reactions to suicides were influenced predominantly by views that suicide is an extraordinary moral evil in the setting. Increased culturally focused suicide education can improve people's understanding and enhance responsive suicide prevention and postvention.
Do Dutch News Reports About Suicide Refer to Suicide Prevention Strategies?
Authors: van Leeuwen Lonneke , Bommelé Jeroen
Published: August 2019

Abstract. Background: Previous research and media guidelines suggest two potential protective characteristics of news reports about suicide: (1) individuals who adopt coping strategies other than suicidal behavior are described and (2) information about resources for support is provided. Aims: Our aim was to investigate the extent to which Dutch news reports contain these two potential protective characteristics. Method: A random selection of Dutch news reports ( N = 296) published in the previous 6 months was coded on the presence of each of the two potential protective characteristics. Results: Of the 296 news reports, 50 news reports (16.9%) mentioned available resources for support. Only one news report (0.3%) described an individual who adopted coping strategies other than suicidal behavior in adverse circumstances, namely, entering a mental health care institution. Limitations: One of the limitations is that, owing to the selection of news reports, conclusions pertain only to news reports published by Dutch media sources with the most readership in that period. Conclusion: The results of this study suggest that current knowledge about protective characteristics of news reports on suicide needs to be better implemented in The Netherlands.
Stimulation of Heterotrophic and Autotrophic Metabolism in the Mixing Zone of the Kuroshio Current and Northern South China Sea: Implications for Export Production
Authors: Huang Yibin , Laws Edward , Chen Bingzhang , Huang Bangqin
Published: August 2019

To evaluate the influences of the Kuroshio Current intrusion on the biogeochemistry of the northern South China Sea (NSCS), we conducted field observations of the responses of microbial metabolism to the intrusions of the Kuroshio Current into the NSCS. We used an isopycnal mixing model to quantitatively assess the extent of the Kuroshio intrusion into the NSCS and found that bacterial abundance, production, and growth efficiency were unimodal functions of the fraction of Kuroshio water. Values were maximal at ~60% Kuroshio water and decreased monotonically as the percent of Kuroshio water deviated from 60%. The patterns of gross primary production and nitrate concentration were similar, but the peaks occurred at ~50% Kuroshio water. The Kuroshio intrusion, however, had little impact on bacterial and community respiration. The observed elevation of nitrate concentrations at ~50% Kuroshio water was quantitatively consistent with estimates of the amount of inorganic nitrogen released by remineralization of dissolved organic nitrogen by bacteria. Based on these observations, we hypothesize that dissolved organic matter in the Kuroshio water stimulates bacterial activity, and catabolism of the dissolved organic matter releases inorganic nutrients that stimulate primary production in the NSCS basin. The concomitant elevation of net community production subsequently enhances export production and thereby strengthens the biological pump in the nitrogen‐limited NSCS basin. Recognition of this mechanism underscores the role of horizontal currents in regional carbon and nitrogen cycles and broadens understanding of the processes that sustain export production in the oligotrophic ocean.
2019 Class of AGU Fellows Announced
Authors: Bell Robin , Holmes Mary
Published: August 2019

AGU is proud to have chosen 62 new Fellows and will honor them at Fall Meeting 2019 in San Francisco, Calif.
Influence of Seasonal Frozen Soil on Near‐Surface Shear Wave Velocity in Eastern Hokkaido, Japan
Authors: Miao Y. , Shi Y. , Zhuang H. Y. , Wang S. Y. , Liu H. B. , Yu X. B.
Published: August 2019

We measured shear wave velocities in the shallow subsurface by applying seismic interferometry to earthquake records from eight vertical borehole arrays in eastern Hokkaido, Japan. We detected an increase of several percent in the seismic velocity during January to March due to seasonal frost dynamics. The velocity changes associated with seasonal frozen soil are affected by the frost depth and the extent of freezing, while the frost depth and the extent of freezing are mainly controlled by the cumulative temperature and the current temperature, respectively. Thus, a weighted cumulative freezing degree day is proposed to consider these two factors and used for stage division of the annual freeze‐thaw cycle. Based on the results of observation, we present an empirical model to relate the velocity changes with the weighted cumulative freezing degree days, which allows us to estimate the influence of seasonal frozen soil on near‐surface seismic velocity.
Prominent Precession Band Variance in ENSO Intensity Over the Last 300,000 Years
Authors: Lu Zhengyao , Liu Zhengyu , Chen Guangshan , Guan Jian
Published: August 2019

Three transient National Center for Atmospheric Research Community Climate System Model, version 3 model simulations were analyzed to study the responses of El Niño–Southern Oscillation (ENSO) and the equatorial Pacific annual cycle (AC) to external forcings over the last 300,000 years. The time‐varying boundary conditions of insolation, greenhouse gases, and continental ice sheets, accelerated by a factor of 100, were sequentially added in these simulations. The simulated ENSO and AC amplitudes change in phase, and both have pronounced precession band variance (~21,000 years). The precession‐modulated slow (orbital time scales) ENSO evolution is dominated linearly by the change of the coupled ocean‐atmosphere instability, notably the Ekman upwelling feedback and thermocline feedback. In contrast, the greenhouse gases and ice sheet forcings (~100,000‐year cycles) are opposed to each other as they influence ENSO variability through changes in AC amplitude via a common nonlinear frequency entrainment mechanism. The acceleration technique could dampen and delay the precession signals below the surface ocean associated with ENSO intensity.
Upper Mantle P and S Wave Velocity Structure of the Kalahari Craton and Surrounding Proterozoic Terranes, Southern Africa
Authors: Ortiz Kameron , Nyblade Andrew , van der Meijde Mark , Paulssen Hanneke , Kwadiba Motsamai , Ntibinyane Onkgopotse , Durrheim Raymond , Fadel Islam , Homman Kyle
Published: August 2019

New broadband seismic data from Botswana and South Africa have been combined with existing data from the region to develop improved P and S wave velocity models for investigating the upper mantle structure of southern Africa. Higher craton‐like velocities are imaged beneath the Rehoboth Province and parts of the northern Okwa Terrane and the Magondi Belt, indicating that the northern edge of the greater Kalahari Craton lithosphere lies along the northern boundary of these terranes. Lower off‐craton velocities are imaged beneath the Damara‐Ghanzi‐Chobe Belt, and may in part reflect thinning of the lithosphere beneath the incipient Okavango Rift. Lower velocities are also imaged to the north and northwest of the Bushveld Complex beneath parts of the Okwa Terrane, Magondi Belt, and Limpopo Belt, indicating that cratonic upper mantle in some areas beneath these terranes may have been modified by the 2.05‐Ga Bushveld and/or 1.1‐Ga Umkondo magmatic events.
Early Indian Summer Monsoon Onset Driven by Low Soil Moisture in the Iranian Desert
Authors: Moon Suyeon , Ha Kyung‐Ja
Published: August 2019

Advancing the leading time for onset prediction of the Indian summer monsoon (ISM) onset is an imperative task; however, it has remained a challenging subject. In particular, the land‐atmosphere coupling associated with monsoon onset prediction is poorly understood. Here we attempt to investigate the land factor as the ISM onset precursor through studying the internal mechanism of atmospheric heating, which is distinguished by monsoon onset. The low (high) soil moisture in the Iranian desert during March and April advances (delays) ISM onset by enhancing (disturbing) the vertical easterly wind shear. In addition, midtropospheric heating is affected by soil moisture in the Iranian desert. By investigating the internal atmospheric heating process and suggesting the relationship between low soil moisture and ISM onset, these findings clarify the monsoon onset mechanism in terms of the vertical atmospheric profile and land‐atmosphere interaction, which eventually extend the lead time for the onset prediction.
Singular Spectral Analysis of the aa and Dst Geomagnetic Indices
Authors: Le Mouël J. L. , Lopes F. , Courtillot V.
Published: August 2019

We apply singular spectrum analysis in order to identify trends and quasi‐periodic oscillations in the aa and Dst series of geomagnetic activity. We also analyze the sunspot number International SunSpot Number (ISSN) and the number of polar faculae Polar Faculae (PF). Singular spectrum analysis provides the eigenvalues and therefore trends and oscillatory components of the four series. ISSN is dominated by a trend (the Gleissberg cycle), followed by 10.6, 35.5 years, two ~8‐year components, 21.4 and 5.3 year. aa shows the same trend, a ~47‐year component, then 10.8, 32.3, 21.8, and a series of three close components at 10.6, 12.2, and 9.2 years, followed by a 6 month seasonal component. PF is dominated by the 20.7‐year period, followed by 10.2, 8.3, 41, and 31 years, then a 5.2 year component. Dst is dominated by a trend, then a strong 6‐month component; next are found a 47‐year component, the 10.6 years and a second seasonal line at 1 year. The ~22‐, ~11‐, and ~5.5‐year components are common to the four indices. These “pseudo harmonic” components are evidence of solar activity. Singular spectrum analysis identifies components that vary in frequency and amplitude. The phase relationships of any two components over time can be studied in detail. An illustration is given by the remarkable phase coherency of the 5.3‐year component. But the components are neither truly periodical nor exact multiples of each other. These differences reflect the complex mechanisms that govern solar‐terrestrial relationships.
Equation of State for Shocked Fe‐8.6 wt% Si up to 240 GPa and 4,670 K
Authors: Huang Haijun , Leng Chunwei , Wang Qingsong , Young Gang , Liu Xun , Wu Ye , Xu Feng , Fei Yingwei
Published: August 2019

Using dynamic compression technique, the equation of state for Fe‐8.6 wt% Si was measured up to 240 GPa and 4,670 K. A least squares fit to the experimental data yields the Hugoniot parameters C0 = 4.603±0.101 km/s and λ = 1.505±0.037 with initial density ρ0=7.386±0.021 g/cm3. Based on the Hugoniot data, the calculated isothermal equation of state is consistent with static compression data when the lattice Grüneisen parameter γl =1.65(7.578/ρ) and electronic Grüneisen parameter γe=1.83. The calculated pressure‐density data at 300 K were fitted to a third‐order Birch‐Murnaghan equation of state with zero pressure the parameters K0=192.1±6.3 GPa,
=4.71±0.27 with fixed ρ0ε =7.578±0.050 g/cm3. Under the conditions of Earth's core, the densities of Fe‐8.6±2.0 wt% Si and Fe‐3.8±2.9 wt% Si agree with preliminary reference Earth mode (PREM) data of the outer and the inner core, respectively. These are the upper limits for Si in the core assuming Si is the only light element. Simultaneously considering the geophysical and geochemical constraints for a Si‐S‐bearing core, the outer core may contain 3.8±2.9 wt% Si and 5.6±3.0 wt% S.
Plio‐Quaternary Outer Forearc Deformation and Mass Balance of the Southern Costa Rica Convergent Margin
Authors: Morell Kristin D. , Fisher Donald M. , Bangs Nathan
Published: August 2019

Identifying the processes that control the rates, magnitudes, and longevity of outer forearc deformation is fundamental to our understanding of how mass is distributed within subduction zone systems. The margin of southern Costa Rica has been the target of numerous onland field studies, geophysical surveys, and the Costa Rica Seismogenesis Project (CRISP) drilling expedition. Despite these extensive data sets, the relative roles that subduction erosion, shortening, and seamount subduction play in shaping the behavior and evolution of the outer forearc remain debated. Here we analyze new and existing geomorphic, geologic, stratigraphic, and geochronologic data sets across the entire forearc‐arc‐backarc system near the Costa Rica Seismogenesis Project transect to test several conceptual models for outer forearc deformation in southern Costa Rica. The results from the compilation agree with a model where recent arcward retreat of the trench (movement of the trench in the direction of the arc) occurs due to underthrusting of the outer forearc beneath the inner forearc, and outer forearc deformation occurs primarily by transient rapid vertical tectonism due to the subduction of bathymetric relief. These results lead to a new conceptual model for Plio‐Quaternary outer forearc deformation in southern Costa Rica that does not require large amounts of net mass loss within the upper plate.
Leaf Wax δD and δ13C in Soils Record Hydrological and Environmental Information Across a Climatic Gradient in Israel
Authors: Goldsmith Yonaton , Polissar Pratigya J. , deMenocal Peter B. , Broecker Wallace S.
Published: August 2019

The hydrogen (δDwax) and carbon (δ13Cwax) isotope compositions of long‐chain alkanes derived from plant waxes record hydrological and environmental conditions. However, the integration of plant n‐alkanes into the sedimentary cycle, the variability of δDwax and δ13Cwax in soils, and the paleoclimate applicability in paleosols and archaeological sediments are poorly constrained. We sampled plants and soils across a steep climate transect in Israel to understand how plant type and environmental parameters shape δ13Cwax and δDwax. This transect has three advantages: existence of long‐term precipitation isotopic composition (δDr) records, a single wet season potentially reduces variability due to seasonality, and abandoned Byzantine period (~300–600 AD) agricultural terraces that reduce modern and ancient soil mixing and provide age constraints. We find that soil δ13Cwax is constant (0.4‰, 1σ) across a 500‐ to 1,300‐mm/year rainfall gradient and appears insensitive to rainfall amount, unlike bulk plant δ13C. The absence of a rainfall effect suggests that δ13Cwax may be better suited to reconstructing C3/C4 plant ratios than bulk δ13C. Homologue average soil δDwax significantly correlate with δDr, and the offset between δDr and soil δDwax (εapp) correlates with growing season relative humidity. The seasonality of leaf production accounted for at most ~10% of total plant δDwax variability. Lastly, soil δDwax and δ13Cwax variability is reduced by ~80% relative to plant δDwax and δ13Cwax variability. Our results show that soil δDwax and δ13Cwax faithfully record δDr and landscape C3‐C4 plant contributions and thus support the utility of these proxy data in paleosols and archaeological sites.
DeepCC: a novel deep learning-based framework for cancer molecular subtype classification
Authors: Gao Feng , Wang Wei , Tan Miaomiao , Zhu Lina , Zhang Yuchen , Fessler Evelyn , Vermeulen Louis , Wang Xin
Published: August 2019

Molecular subtyping of cancer is a critical step towards more individualized therapy and provides important biological insights into cancer heterogeneity. Although gene expression signature-based classification has been widely demonstrated to be an effective approach in the last decade, the widespread implementation has long been limited by platform differences, batch effects, and the difficulty to classify individual patient samples. Here, we describe a novel supervised cancer classification framework, deep cancer subtype classification (DeepCC), based on deep learning of functional spectra quantifying activities of biological pathways. In two case studies about colorectal and breast cancer classification, DeepCC classifiers and DeepCC single sample predictors both achieved overall higher sensitivity, specificity, and accuracy compared with other widely used classification methods such as random forests (RF), support vector machine (SVM), gradient boosting machine (GBM), and multinomial logistic regression algorithms. Simulation analysis based on random subsampling of genes demonstrated the robustness of DeepCC to missing data. Moreover, deep features learned by DeepCC captured biological characteristics associated with distinct molecular subtypes, enabling more compact within-subtype distribution and between-subtype separation of patient samples, and therefore greatly reduce the number of unclassifiable samples previously. In summary, DeepCC provides a novel cancer classification framework that is platform independent, robust to missing data, and can be used for single sample prediction facilitating clinical implementation of cancer molecular subtyping.
Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to Rituximab
Authors: Serra-Peinado Carla , Grau-Expósito Judith , Luque-Ballesteros Laura , Astorga-Gamaza Antonio , Navarro Jordi , Gallego-Rodriguez Jenny , Martin Mario , Curran Adrià , Burgos Joaquin , Ribera Esteban , Raventós Berta , Willekens Rein , Torrella Ariadna , Planas Bibiana , Badía Rosa , Garcia Felipe , Castellví Josep , Genescà Meritxell , Falcó Vicenç , Buzon Maria J.
Published: August 2019

The identification of exclusive markers to target HIV-reservoir cells will represent a significant advance in the search for therapies to cure HIV. Here, we identify the B lymphocyte antigen CD20 as a marker for HIV-infected cells in vitro and in vivo. The CD20 molecule is dimly expressed in a subpopulation of CD4-positive (CD4+) T lymphocytes from blood, with high levels of cell activation and heterogeneous memory phenotypes. In lymph node samples from infected patients, CD20 is present in productively HIV-infected cells, and ex vivo viral infection selectively upregulates the expression of CD20 during early infection. In samples from patients on antiretroviral therapy (ART) this subpopulation is significantly enriched in HIV transcripts, and the anti-CD20 monoclonal antibody Rituximab induces cell killing, which reduces the pool of HIV-expressing cells when combined with latency reversal agents. We provide a tool for targeting this active HIV-reservoir after viral reactivation in patients while on ART.
N-glycosylation-defective splice variants of neuropilin-1 promote metastasis by activating endosomal signals
Authors: Huang Xiuping , Ye Qing , Chen Min , Li Aimin , Mi Wenting , Fang Yuxin , Zaytseva Yekaterina Y. , O’Connor Kathleen L. , Vander Kooi Craig W. , Liu Side , She Qing-Bai
Published: August 2019

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent signals to activate the FAK/p130Cas pathway, thereby promoting CRC cell migration, invasion and metastasis. Blocking endocytosis or endosomal Met/β1-integrin/FAK signaling profoundly inhibits the oncogenic effects of both NRP1 variants. These findings reveal an important role for these NRP1 splice variants in the regulation of endocytic trafficking for cancer cell dissemination.
3D sub-diffraction imaging in a conventional confocal configuration by exploiting super-linear emitters
Authors: Denkova Denitza , Ploschner Martin , Das Minakshi , Parker Lindsay M. , Zheng Xianlin , Lu Yiqing , Orth Antony , Packer Nicolle H. , Piper James A.
Published: August 2019

Sub-diffraction microscopy enables bio-imaging with unprecedented clarity. However, most super-resolution methods require complex, costly purpose-built systems, involve image post-processing and struggle with sub-diffraction imaging in 3D. Here, we realize a conceptually different super-resolution approach which circumvents these limitations and enables 3D sub-diffraction imaging on conventional confocal microscopes. We refer to it as super-linear excitation-emission (SEE) microscopy, as it relies on markers with super-linear dependence of the emission on the excitation power. Super-linear markers proposed here are upconversion nanoparticles of NaYF4, doped with 20% Yb and unconventionally high 8% Tm, which are conveniently excited in the near-infrared biological window. We develop a computational framework calculating the 3D resolution for any viable scanning beam shape and excitation-emission probe profile. Imaging of colominic acid-coated upconversion nanoparticles endocytosed by neuronal cells, at resolutions twice better than the diffraction limit both in lateral and axial directions, illustrates the applicability of SEE microscopy for sub-cellular biology.
A [13]rotaxane assembled via a palladium molecular capsule
Authors: Ferrando-Soria Jesus , Fernandez Antonio , Asthana Deepak , Nawaz Selina , Vitorica-Yrezabal Iñigo J. , Whitehead George F. S. , Muryn Christopher A. , Tuna Floriana , Timco Grigore A. , Burton Neil D. , Winpenny Richard E. P.
Published: August 2019

Molecules that are the size of small proteins are difficult to make. The most frequently examined route is via self-assembly, and one particular approach involves molecular nanocapsules, where ligands are designed that will enforce the formation of specific polyhedra of metals within the core of the structure. Here we show that this approach can be combined with mechanically interlocking molecules to produce nanocapsules that are decorated on their exterior. This could be a general route to very large molecules, and is exemplified here by the synthesis and structural characterization of a [13]rotaxane, containing 150 metal centres. Small angle X-ray scattering combined with atomistic molecular dynamics simulations demonstrate the compound is intact in solution.
Chemical compass behaviour at microtesla magnetic fields strengthens the radical pair hypothesis of avian magnetoreception
Authors: Kerpal Christian , Richert Sabine , Storey Jonathan G. , Pillai Smitha , Liddell Paul A. , Gust Devens , Mackenzie Stuart R. , Hore P. J. , Timmel Christiane R.
Published: August 2019

The fact that many animals, including migratory birds, use the Earth’s magnetic field for orientation and compass-navigation is fascinating and puzzling in equal measure. The physical origin of these phenomena has not yet been fully understood, but arguably the most likely hypothesis is based on the radical pair mechanism (RPM). Whilst the theoretical framework of the RPM is well-established, most experimental investigations have been conducted at fields several orders of magnitude stronger than the Earth’s. Here we use transient absorption spectroscopy to demonstrate a pronounced orientation-dependence of the magnetic field response of a molecular triad system in the field region relevant to avian magnetoreception. The chemical compass response exhibits the properties of an inclination compass as found in migratory birds. The results underline the feasibility of a radical pair based avian compass and also provide further guidelines for the design and operation of exploitable chemical compass systems.
RETRACTED ARTICLE: Mechanically interlocked architecture aids an ultra-stiff and ultra-hard elastically bendable cocrystal
Authors: Dey Somnath , Das Susobhan , Bhunia Surojit , Chowdhury Rituparno , Mondal Amit , Bhattacharya Biswajit , Devarapalli Ramesh , Yasuda Nobuhiro , Moriwaki Taro , Mandal Kapil , Mukherjee Goutam Dev , Reddy C. Malla
Published: August 2019

Molecular crystals are not known to be as stiff as metals, composites and ceramics. Here we report an exceptional mechanical stiffness and high hardness in a known elastically bendable organic cocrystal [caffeine (CAF), 4-chloro-3-nitrobenzoic acid (CNB) and methanol (1:1:1)] which is comparable to certain low-density metals. Spatially resolved atomic level studies reveal that the mechanically interlocked weak hydrogen bond networks which are separated by dispersive interactions give rise to these mechanical properties. Upon bending, the crystals significantly conserve the overall energy by efficient redistribution of stress while perturbations in hydrogen bonds are compensated by strengthened π-stacking. Furthermore we report a remarkable stiffening and hardening in the elastically bent crystal. Hence, mechanically interlocked architectures provide an unexplored route to reach new mechanical limits and adaptability in organic crystals. This proof of concept inspires the design of light-weight, stiff crystalline organics with potential to rival certain inorganics, which currently seem inconceivable.
On demand delivery and analysis of single molecules on a programmable nanopore-optofluidic device
Authors: Rahman M. , Stott M. A. , Harrington M. , Li Y. , Sampad M. J. N. , Lancaster L. , Yuzvinsky T. D. , Noller H. F. , Hawkins A. R. , Schmidt H.
Published: August 2019

Nanopore-based single nanoparticle detection has recently emerged as a vibrant research field with numerous high-impact applications. Here, we introduce a programmable optofluidic chip for nanopore-based particle analysis: feedback-controlled selective delivery of a desired number of biomolecules and integration of optical detection techniques on nanopore-selected particles. We demonstrate the feedback-controlled introduction of individual biomolecules, including 70S ribosomes, DNAs and proteins into a fluidic channel where the voltage across the nanopore is turned off after a user-defined number of single molecular insertions. Delivery rates of hundreds/min with programmable off-times of the pore are demonstrated using individual 70S ribosomes. We then use real-time analysis of the translocation signal for selective voltage gating of specific particles from a mixture, enabling selection of DNAs from a DNA-ribosome mixture. Furthermore, we report optical detection of nanopore-selected DNA molecules. These capabilities point the way towards a powerful research tool for high-throughput single-molecule analysis on a chip.
Integrated 9Be+ multi-qubit gate device for the ion-trap quantum computer
Authors: Hahn H. , Zarantonello G. , Schulte M. , Bautista-Salvador A. , Hammerer K. , Ospelkaus C.
Published: August 2019

We demonstrate the experimental realization of a two-qubit Mølmer–Sørensen gate on a magnetic field-insensitive hyperfine transition in 9Be+ ions using microwave near-fields emitted by a single microwave conductor embedded in a surface-electrode ion trap. The design of the conductor was optimized to produce a high oscillating magnetic field gradient at the ion position. The measured gate fidelity is determined to be 98.2 ± 1.2% and is limited by technical imperfections, as is confirmed by a comprehensive numerical error analysis. The conductor design can potentially simplify the implementation of multi-qubit gates and represents a self-contained, scalable module for entangling gates within the quantum CCD architecture for an ion-trap quantum computer.
Creating a surrogate commuter network from Australian Bureau of Statistics census data
Authors: Fair Kristopher M. , Zachreson Cameron , Prokopenko Mikhail
Published: August 2019

Between the 2011 and 2016 national censuses, the Australian Bureau of Statistics changed its anonymity policy compliance system for the distribution of census data. The new method has resulted in dramatic inconsistencies when comparing low-resolution data to aggregated high-resolution data. Hence, aggregated totals do not match true totals, and the mismatch gets worse as the data resolution gets finer. Here, we address several aspects of this inconsistency with respect to the 2016 usual-residence to place-of-work travel data. We introduce a re-sampling system that rectifies many of the artifacts introduced by the new ABS protocol, ensuring a higher level of consistency across partition sizes. We offer a surrogate high-resolution 2016 commuter dataset that reduces the difference between the aggregated and true commuter totals from ~34% to only ~7%, which is on the order of the discrepancy across partition resolutions in data from earlier years.
HBcAb seropositivity is correlated with poor HIV viremia control in an Italian cohort of HIV/HBV-coinfected patients on first-line therapy
Authors: Malagnino Vincenzo , Cerva Carlotta , Maffongelli Gaetano , Teti Elisabetta , Foroghi Biland Luca , Cesta Novella , De Masi Margherita , Stingone Christof , Armenia Daniele , Svicher Valentina , Salpini Romina , Andreoni Massimo , Sarmati Loredana
Published: August 2019

The morbidity and mortality rates of human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfection are higher than that of either infection alone. Outcomes and the virological response to antiretrovirals (combination antiretroviral therapy, cART) were explored in HIV/HBV subjects in a cohort of Italian patients treated with cART. A single-center retrospective analysis of patients enrolled from January 2007 to June 2018 was conducted by grouping patients by HBV status and recording baseline viro-immunological features, the history of virological failure, the efficacy of cART in achieving HIV viral undetectability, viral blip detection and viral rebound on follow up. Among 231 enrolled patients, 10 (4.3%) were HBV surface (s) antigen (HBsAg)-positive, 85 (36.8%) were positive for antibodies to HBV c antigen (HBcAb) and with or without antibodies to HBV s antigen (HBsAb), and 136 were (58.9%) HBV-negative. At baseline, HBcAb/HBsAb+/−-positive patients had lower CD4+ cell counts and CD4+ nadirs (188 cell/mmc, IQR 78–334, p = 0.02 and 176 cell/mmc, IQR 52–284, p = 0,001, respectively). There were significantly higher numbers of AIDS and non-AIDS events in the HBcAb+/HBsAb+/−-positive subjects than in the HBV-negative patients (41.1% vs 19.1%, p = 0.002 and 56.5% vs 28.7%, respectively, p ≤ 0.0001); additionally, HIV viremia undetectability was achieved a significantly longer time after cART was begun in the former than in the latter population (6 vs 4 months, p = 0.0001). Cox multivariable analysis confirmed that after starting cART, an HBcAb+/HBsAb+/−-positive status is a risk factor for a lower odds of achieving virological success and a higher risk of experiencing virological rebound (AHR 0.63, CI 95% 0.46–0.87, p = 0.004 and AHR 2.52, CI 95% 1.09–5.80, p = 0.030). HBcAb-positive status resulted in a delay in achieving HIV < 50 copies/mL and the appearance of viral rebound in course of cART, hence it is related to a poor control of HIV infection in a population of coinfected patients.