bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental investigation of liquid film cooling in hypersonic flow
Authors: Yuan Chaokai , Li Jinping , Jiang Zonglin , Yu Hongru
Published: April 2019

Film cooling is generally considered as a promising active cooling technology for developing thermal protection systems of hypersonic vehicles; however, most of experimental and numerical studies of film cooling mainly concentrated on gaseous film cooling. Since the phase change of liquid coolants can absorb a large amount of latent heat, liquid film cooling should have more potential advantages, especially for severe environments accompanied by hypersonic flight. To address this issue, the film cooling using water as a coolant was experimentally investigated in hypersonic flow. Experiments were carried out in a detonation tunnel, at a hypersonic Mach number of 6 using a 25° apex-angle wedge. Characteristic physical quantities, such as surface temperature rise, shock wave structure, film thickness, and cover area, are measured by thermocouples, schlieren, and a specially devised liquid film measurement system. The experimental results verify that the liquid film cooling is feasible in hypersonic flow and also indicate that it is featured with maintaining aerodynamic performances due to the weak effect on the main flow caused by coolant injection. Inspired by these results, liquid film flow characteristics and its influencing factors including mass flow rate, dynamic pressure, coolant injection direction, and surface tension are investigated to guide the design of a thermal protection system.
Wave profile along a ship hull, short farfield waves, and broad inner Kelvin wake sans divergent waves
Authors: Wu Huiyu , Wu Jianwei , He Jiayi , Zhu Renchuan , Yang Chen-Jun , Noblesse Francis
Published: April 2019

The Neumann-Michell linear potential flow theory of the short farfield waves created by a ship that advances at a constant speed in calm water is coupled with nonlinear analytical relations for inviscid flow along the wave profile at the ship hull surface, i.e., the contact line between the ship hull surface and the free surface. This ad hoc coupling of linear farfield ship waves and a nonlinear nearfield flow along a ship waterline determines short farfield ship waves in terms of the free-surface elevation along the ship hull surface, and provides insight into the influence of nearfield nonlinearities (most significant at a ship waterline) on short farfield ship waves. For the Wigley parabolic ship model, nearfield nonlinearities are found to be relatively weak and to have a limited, although appreciable, influence on short farfield waves. The steepness of divergent ship waves is also analyzed. This analysis shows that, for a full-scale Wigley hull, divergent waves are too steep to exist inside a broad inner Kelvin wake with angle roughly equal to 13°, i.e., a third of Kelvin’s 39° ship wake angle.
Quantitative assessment of cerebral connectivity deficiency and cognitive impairment in children with prenatal alcohol exposure
Authors: Gao Lin , Grebogi Celso , Lai Ying-Cheng , Stephen Julia , Zhang Tongsheng , Li Yuanli , Ren Haipeng , Li Dichen , Wang Jue , Schelter Bjoern , Sommerlade Linda
Published: April 2019

It is common knowledge that alcohol consumption during pregnancy would cause cognitive impairment in children. However, recent works suggested that the risk of drinking during pregnancy may have been exaggerated. It is critical to determine whether and up to which amount the consumption of alcohol will affect the cognitive development of children. We evaluate time-varying functional connectivity using magnetoencephalogram data from somatosensory evoked response experiments for 19 teenage subjects with prenatal alcohol exposure and 21 healthy control teenage subjects using a new time-varying connectivity approach, combining renormalised partial directed coherence with state space modeling. Children exposed to alcohol prenatally are at risk of developing a Fetal Alcohol Spectrum Disorder (FASD) characterized by cerebral connectivity deficiency and impaired cognitive abilities. Through a comparison study of teenage subjects exposed to alcohol prenatally with healthy control subjects, we establish that the inter-hemispheric connectivity is deficient for the former, which may lead to disruption in the cortical inter-hemispheric connectivity and deficits in higher order cognitive functions as measured by an IQ test, for example. We provide quantitative evidence that the disruption is correlated with cognitive deficits. These findings could lead to a novel, highly sensitive biomarker for FASD and support a recommendation of no safe amount of alcohol consumption during pregnancy.
Energy distribution functions for ions from pulsed EUV-induced plasmas in low pressure N2-diluted H2 gas
Authors: Beckers J. , van de Ven T. H. M. , de Meijere C. A. , van der Horst R. M. , van Kampen M. , Banine V. Y.
Published: April 2019

The operation of Extreme Ultraviolet (EUV) lithography scanners inherently goes hand-in-hand with the creation of highly transient pulsed plasmas in the optical path of these tools. These so-called EUV-induced plasmas are created upon photoionization events when a pulsed beam of EUV photons travels through the low pressure background gas. It is fully recognized by the lithography industry that EUV-induced plasmas may significantly impact the quality and life-time of expensive and delicate optical elements in the scanner. Research efforts into EUV-induced plasmas impacting plasma-facing surfaces have so far been limited to pure hydrogen (H2) plasmas. However, this hydrogen background gas may occasionally be diluted with a small fraction of another molecular gas such as nitrogen (N2). The impact on the relevant plasma parameters of such molecular contaminants has remained unknown until now. In this letter, we put forward measurements of energy-resolved fluxes of (positive) hydrogen ions, nitrogen ions, and hydrogen-nitrogen ions created in a pulsed N2-diluted EUV-induced plasma in H2 at approximately 5 Pa (typical EUV lithography scanner conditions). The data have been obtained using an electrostatic quadrupole plasma analyzer and show that although the N2-dilution fraction is small (∼2 × 10−3) compared to the H2 partial pressure, implications for the ion flux out of the plasma and the composition thereof are significant. Since the mass of nitrogen-containing ions is much higher in comparison to that of their hydrogen counterparts, and because of their potential chemical activity, this effect has to be taken into account while studying the surface impact of EUV-induced plasmas.
Impact of (nano)formulations on the distribution and wash-off of copper pesticides and fertilisers applied on citrus leaves
Authors: Kah Melanie , Navarro Divina , Kookana Rai S. , Kirby Jason K. , Santra Swadeshmukul , Ozcan Ali , Kabiri Shervin
Published: April 2019

Environmental contextThere are great concerns around current wide usage of copper-based agrochemicals. We compare the fate of nano- and conventional forms of copper, in particular their resistance to wash-off by rain (rainfastness), following their application to citrus leaves. Results showing large differences between the formulations in the amount and forms of copper washed from the leaves provide essential information to optimise agrochemical efficacy while minimising the environmental impact. AbstractThis study compares the rainfastness of nine forms of Cu, including nano and conventional Cu-based fungicide formulations, as well as their salt or bulk equivalents. Rainfastness is the ability to resist wash-off; it is a key property for improving pesticide formulations and for assessing the potential transfer of pesticides to the soil. A new protocol was developed to characterise losses of Cu from treated leaves. It consisted of dipping the leaves in rainwater and then in an acid/ethanol mixture followed by size fractionation. The proportion of Cu lost by wash-off from citrus leaves ranged from <2% (Tribasic, nCuO or Cu(OH)2) up to 93% (CuSO4) of the initial amount of Cu applied. Intermediate Cu losses were observed for formulations with silica (nano)particles (9–14% of applied Cu), Kocide (22%), ChampDP (31%), and a formulation with graphene oxide (47%). Smaller particles generally resulted in less wash-off, possibly due to stronger attachment to the leaf surface, but other factors such as the particle shape and solubility also played an essential role. The retention of nCuO to the leaves was particularly high, and the exact mechanisms involved (e.g. foliar uptake) deserve further work. Most of the Cu was washed off in its ionic form (>74%). Two Cu formulations (one commercial formulation and the formulation with graphene oxide) also showed wash off in significant proportions of Cu (~17%) in the nano-sized fraction. This study provides essential information on the amounts and forms of Cu that may reach the soil after the application of Cu-based agrochemicals. The great diversity in behaviour across the range of formulations considered highlights the need for more systematic research to fully exploit the potential improvements of current agrochemicals through (nano)formulation technologies.
Daisy-chain gene drives for the alteration of local populations
Authors: Noble Charleston , Min John , Olejarz Jason , Buchthal Joanna , Chavez Alejandro , Smidler Andrea L. , DeBenedictis Erika A. , Church George M. , Nowak Martin A. , Esvelt Kevin M.
Published: April 2019

If they are able to spread in wild populations, CRISPR-based gene-drive elements would provide new ways to address ecological problems by altering the traits of wild organisms, but the potential for uncontrolled spread tremendously complicates ethical development and use. Here, we detail a self-exhausting form of CRISPR-based drive system comprising genetic elements arranged in a daisy chain such that each drives the next. “Daisy-drive” systems can locally duplicate any effect achievable by using an equivalent self-propagating drive system, but their capacity to spread is limited by the successive loss of nondriving elements from one end of the chain. Releasing daisy-drive organisms constituting a small fraction of the local wild population can drive a useful genetic element nearly to local fixation for a wide range of fitness parameters without self-propagating spread. We additionally report numerous highly active guide RNA sequences sharing minimal homology that may enable evolutionarily stable daisy drive as well as self-propagating CRISPR-based gene drive. Especially when combined with threshold dependence, daisy drives could simplify decision-making and promote ethical use by enabling local communities to decide whether, when, and how to alter local ecosystems.
Cryoprotectant-free cryopreservation of mammalian cells by superflash freezing
Authors: Akiyama Yoshitake , Shinose Masato , Watanabe Hiroki , Yamada Shigeru , Kanda Yasunari
Published: April 2019

Significance

Cryopreservation is routinely used for the long-term storage of cells in various areas of academic, industrial, and clinical research. To keep frozen cells alive, it is necessary to vitrify (or nanocrystallize) water on the inside and outside of the cells. Vitrification is conventionally achieved by adding at least one cryoprotective agent (CPA) to the medium. However, CPAs should ideally be avoided due to their cytotoxicity and potential side effects on the cells. Herein, we demonstrate a method of CPA-free cryopreservation, in which cells are almost vitrified by ultrarapid cooling using inkjet printing. The freezing method should be generally suitable for all kinds of cells that are susceptible to CPAs, including stem cells.
Multicentury perspective assessing the sustainability of the historical harvest of seaducks
Authors: Hargan Kathryn E. , Gilchrist H. Grant , Clyde Nikolas M. T. , Iverson Samuel A. , Forbes Mark R. , Kimpe Linda E. , Mallory Mark L. , Michelutti Neal , Smol John P. , Blais Jules M.
Published: April 2019

Significance

The paucity of monitoring data for seabird populations at suitable temporal and spatial scales challenges the development of realistic and effective conservation policies. We employ newly developed paleoenvironmental techniques at 10 key subarctic seaduck colonies to reconstruct broadscale population changes at decadal timescales through the 20th century. We show that harvesting practices in southwestern Greenland and northeastern Canada were unsustainable, timed with the advent of widespread use of shotguns and outboard motors for hunting across the North. Our historical population reconstructions, corroborated with two independent proxies (sterols and stable nitrogen isotopes), reaffirms that hunting restrictions were necessary to prevent the collapse of this subspecies.
Repertoires of G protein-coupled receptors for
Ciona
-specific neuropeptides
Authors: Shiraishi Akira , Okuda Toshimi , Miyasaka Natsuko , Osugi Tomohiro , Okuno Yasushi , Inoue Jun , Satake Honoo
Published: April 2019

Significance

Elucidation of neuropeptide–receptor pairs is essential for the investigation of peptidergic signalling processes. Although sequence alignment and molecular phylogenetic analysis can easily predict G protein-coupled receptors for homologous neuropeptides, these methods cannot predict receptors for novel peptides, so many neuropeptide–receptor pairs remain to be identified. We used our original machine-learning system, peptide descriptor-incorporated support vector machine, to predict multiple neuropeptide–receptor pairs of the vertebrate sister group,
Ciona robusta
. The
Ciona
-specific neuropeptide–receptor pairs were validated with cell-based pharmacological assays, showing biological roles for the neuropeptides in a model protochordate. Because of the critical phylogenetic position of
Ciona
, the present study also elucidates the evolutionary processes underlying neuropeptidergic systems in chordates.
Peptidoglycan hydrolase of an unusual cross-link cleavage specificity contributes to bacterial cell wall synthesis
Authors: Chodisetti Pavan Kumar , Reddy Manjula
Published: April 2019

Significance

Bacteria contain peptidoglycan (PG) in their cell envelope to protect them against intracellular osmotic pressure and environmental stress. PG is a large elastic polymer made up of glycan strands interlinked by short peptide chains that form a mesh-like sacculus. In many bacteria, the peptide cross-links are of two types: the predominant
d
-alanine−
meso
-diaminopimelic acid (mDAP) and the rare mDAP−mDAP cross-links. Here, we report the importance of mDAP cross-links in PG synthesis during cell growth by identifying a previously unknown hydrolytic enzyme that cleaves such cross-links in the PG sacculi of
Escherichia coli
. In summary, this study clarifies the role of PG hydrolysis in bacterial cell wall synthesis, thereby rendering it an alternative drug target for development of new antimicrobial agents.
Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice
Authors: Xie Yushu Joy , Dougan Michael , Jailkhani Noor , Ingram Jessica , Fang Tao , Kummer Laura , Momin Noor , Pishesha Novalia , Rickelt Steffen , Hynes Richard O. , Ploegh Hidde
Published: April 2019

Significance

Despite its success in treating hematological cancers, chimeric antigen receptor (CAR) T cell therapy does not so easily eliminate solid tumors. Solid tumors generally develop in a highly immunosuppressive environment and are difficult to target, mostly due to a lack of tumor-specific antigen expression, but other factors contribute as well. This study develops a strategy to target multiple solid tumor types through markers in their microenvironment. The use of single-domain antibody (VHH)-based chimeric antigen receptor (CAR) T cells that recognize these markers circumvents the need for tumor-specific targets. VHH-based CAR T cells that target the tumor microenvironment through immune checkpoint receptors or through stroma and ECM markers are effective against solid tumors in syngeneic, immunocompetent animal models.
Chemical synthesis rewriting of a bacterial genome to achieve design flexibility and biological functionality
Authors: Venetz Jonathan E. , Del Medico Luca , Wölfle Alexander , Schächle Philipp , Bucher Yves , Appert Donat , Tschan Flavia , Flores-Tinoco Carlos E. , van Kooten Mariëlle , Guennoun Rym , Deutsch Samuel , Christen Matthias , Christen Beat
Published: April 2019

Understanding how to program biological functions into artificial DNA sequences remains a key challenge in synthetic genomics. Here, we report the chemical synthesis and testing of
Caulobacter ethensis-2.0
(
C. eth-2.0
), a rewritten bacterial genome composed of the most fundamental functions of a bacterial cell. We rebuilt the essential genome of
Caulobacter crescentus
through the process of chemical synthesis rewriting and studied the genetic information content at the level of its essential genes. Within the 785,701-bp genome, we used sequence rewriting to reduce the number of encoded genetic features from 6,290 to 799. Overall, we introduced 133,313 base substitutions, resulting in the rewriting of 123,562 codons. We tested the biological functionality of the genome design in
C. crescentus
by transposon mutagenesis. Our analysis revealed that 432 essential genes of
C. eth-2.0
, corresponding to 81.5% of the design, are equal in functionality to natural genes. These findings suggest that neither changing mRNA structure nor changing the codon context have significant influence on biological functionality of synthetic genomes. Discovery of 98 genes that lost their function identified essential genes with incorrect annotation, including a limited set of 27 genes where we uncovered noncoding control features embedded within protein-coding sequences. In sum, our results highlight the promise of chemical synthesis rewriting to decode fundamental genome functions and its utility toward the design of improved organisms for industrial purposes and health benefits.
Ephemeral states in protein folding under force captured with a magnetic tweezers design
Authors: Tapia-Rojo Rafael , Eckels Edward C. , Fernández Julio M.
Published: April 2019

Significance

Mechanical signals in biology are complex and change rapidly in the millisecond timescale. Current force spectroscopy instrumentation is limited to constant forces and slowly changing ramps. Here we introduce a force spectrometer that uses a commercial tape head to create a magnetic field that can deliver large and rapidly changing force signals with submillisecond time resolution. We demonstrate the stability of this force spectrometer by measuring the folding dynamics of ultrasensitive talin protein and its speed by capturing the ephemeral molten globule states of protein L. Our instrument opens the study of protein dynamics under realistic perturbations that combine, for example, mechanical noise and periodic forces, such as those experienced in cellular mechanosensing systems.
BRCA1/BARD1-dependent ubiquitination of NF2 regulates Hippo-YAP1 signaling
Authors: Verma Sachin , Yeddula Narayana , Soda Yasushi , Zhu Quan , Pao Gerald , Moresco James , Diedrich Jolene K. , Hong Audrey , Plouffe Steve , Moroishi Toshiro , Guan Kun-Liang , Verma Inder M.
Published: April 2019

Significance

Normal cells harbor protective mechanisms to sense DNA damage, halt cell growth, and repair chromatin lesions to maintain genomic stability. How mitogen signaling in proliferating cells is affected upon BRCA1 loss as part of these protective checkpoints is an intriguing question. This study reveals a unique finding of linking BRCA1 to Hippo signaling pathway to explain this conundrum. Our work shows that serum-responsive expression of BRCA1 is required for YAP1 stability. Ubiquitination of NF2 by BRCA1/BARD1 in proliferating cells inhibits NF2/LATS association and Hippo signaling. These findings suggest Hippo signaling activation as a protective barrier in BRCA1-deficient cells, which upon inactivation, promotes cell proliferation and tumorigenesis.
Tropical cyclone activity affected by volcanically induced ITCZ shifts
Authors: Pausata Francesco S. R. , Camargo Suzana J.
Published: April 2019

Significance

Volcanic eruptions can inject a large amount of aerosol particles, which interact with solar radiation and consequently can affect the climate worldwide, hence the intensity and frequency of extreme events for a few years following the eruption. However, only a handful of studies have investigated the impacts of volcanic eruptions on tropical cyclone activity. Through a set of sensitivity modeling experiments, our study demonstrates that volcanic eruptions by shifting the Intertropical convergence zone can impact tropical cyclone activity up to 4 years following the eruption. These results will prove valuable to society, allowing us to better prepare for the consequences of changes in tropical cyclone activity following large volcanic eruptions.
Spontaneous ribosomal translocation of mRNA and tRNAs into a chimeric hybrid state
Authors: Zhou Jie , Lancaster Laura , Donohue John Paul , Noller Harry F.
Published: April 2019

The elongation factor G (EF-G)–catalyzed translocation of mRNA and tRNA through the ribosome is essential for vacating the ribosomal A site for the next incoming aminoacyl-tRNA, while precisely maintaining the translational reading frame. Here, the 3.2-Å crystal structure of a ribosome translocation intermediate complex containing mRNA and two tRNAs, formed in the absence of EF-G or GTP, provides insight into the respective roles of EF-G and the ribosome in translocation. Unexpectedly, the head domain of the 30S subunit is rotated by 21°, creating a ribosomal conformation closely resembling the two-tRNA chimeric hybrid state that was previously observed only in the presence of bound EF-G. The two tRNAs have moved spontaneously from their A/A and P/P binding states into ap/P and pe/E states, in which their anticodon loops are bound between the 30S body domain and its rotated head domain, while their acceptor ends have moved fully into the 50S P and E sites, respectively. Remarkably, the A-site tRNA translocates fully into the classical P-site position. Although the mRNA also undergoes movement, codon–anticodon interaction is disrupted in the absence of EF-G, resulting in slippage of the translational reading frame. We conclude that, although movement of both tRNAs and mRNA (along with rotation of the 30S head domain) can occur in the absence of EF-G and GTP, EF-G is essential for enforcing coupled movement of the tRNAs and their mRNA codons to maintain the reading frame.
Vocabulary in Traditional Chinese Medicine
Authors: Lu Cailing , Coxhead Averil
Published: April 2019

This article reports on a corpus-based study of Traditional Chinese Medicine (TCM) vocabulary. It first provides a vocabulary profile of English-medium Traditional Chinese Medicine textbooks and journal articles using Nation’s (2012) British National Corpus/Corpus of Contemporary American English (BNC/COCA 25,000) frequency word lists and supplementary word lists of proper nouns, abbreviations, and compounds. Then, it categorizes items outside Nation’s BNC/COCA into Chinese loan words (e.g., qi, yang) and medical lexis (e.g., cinnamomi, rehmanniae), which cover 5.93% of the TCM Corpora in total. The next analysis focuses on Schmitt and Schmitt’s (2014) high, mid, low-frequency vocabulary framework and how it differs from Western medicine. Finally, a vocabulary load analysis shows that to reach 98%, 13,000 word families plus four supplementary lists and two TCM-specific lists are needed. Together, these analyses provide us with a rounded picture of TCM vocabulary. Implications for pedagogy and suggestions for future research follow.
Desires matter! Desired attitudes predict behavioural intentions in people who think abstractly: the case of eating products without added salt / ¡Los deseos importan! Las actitudes deseadas predicen las intenciones de comportamiento en las personas que piensan de modo abstracto: El caso del consumo de alimentos sin sal añadida
Authors: Carrera Pilar , Fernandez-Sedano Itziar , Muñoz Dolores , Caballero Amparo
Published: April 2019

Introduction. Previous research supports that congruence in the construal level between a person’s mindset and predictors enhanced the strength of predictions. Because desired attitudes are more abstract than actual attitudes, we expected that desired attitudes would better predict behavioural intentions in people who present an abstract style of thinking. Objective. We tested this matching effect between desired attitudes and abstractness by measuring the construal level as a person’s base-rate tendency. Method. Participants ( N = 105) reported their past experience and actual and desired attitudes towards eating products without added salt and their behavioural intentions. To classify participants according to an abstract or a concrete way of thinking, their first thought was coded using the linguistic category model (LCM). Results. The simple slopes analysis showed that desired attitudes significantly influenced behavioural intentions for participants with an abstract way of thinking. Conclusion. Our results support the relevance of desired attitudes in terms of behavioural predictions and extend the role of the construal level in the prediction and promotion of desirable but demanding behaviour in the framework of individual differences.
Designing stakeholder learning dialogues for effective global governance
Authors: Cashore Benjamin , Bernstein Steven , Humphreys David , Visseren-Hamakers Ingrid , Rietig Katharine
Published: April 2019

A growing scholarship on multistakeholder learning dialogues suggests the importance of closely managing learning processes to help stakeholders anticipate which policies are likely to be effective. Much less work has focused on how to manage effective transnational multistakeholder learning dialogues, many of which aim to help address critical global environmental and social problems such as climate change or biodiversity loss. They face three central challenges. First, they rarely shape policies and behaviors directly, but work to ‘nudge’ or ‘tip the scales’ in domestic settings. Second, they run the risk of generating ‘compromise’ approaches incapable of ameliorating the original problem definition for which the dialogue was created. Third, they run the risk of being overly influenced, or captured, by powerful interests whose rationale for participating is to shift problem definitions or narrow instrument choices to those innocuous to their organizational or individual interests. Drawing on policy learning scholarship, we identify a six-stage learning process for anticipating effectiveness designed to minimize these risks while simultaneously fostering innovative approaches for meaningful and longlasting problem solving: Problem definition assessments; Problem framing; Developing coalition membership; Causal framework development; Scoping exercises; Knowledge institutionalization. We also identify six management techniques within each process for engaging transnational dialogues around problem solving. We show that doing so almost always requires anticipating multiple-step causal pathways through which influence of transnational and/or international actors and institutions might occur.
Extracellular vesicle measurements with nanoparticle tracking analysis – An accuracy and repeatability comparison between NanoSight NS300 and ZetaView
Authors: Bachurski Daniel , Schuldner Maximiliane , Nguyen Phuong‐Hien , Malz Alexandra , Reiners Katrin S , Grenzi Patricia C , Babatz Felix , Schauss Astrid C , Hansen Hinrich P , Hallek Michael , von Strandmann Elke Pogge
Published: April 2019

The expanding field of extracellular vesicle (EV) research needs reproducible and accurate methods to characterize single EVs. Nanoparticle Tracking Analysis (NTA) is commonly used to determine EV concentration and diameter. As the EV field is lacking methods to easily confirm and validate NTA data, questioning the reliability of measurements remains highly important. In this regard, a comparison addressing measurement quality between different NTA devices such as Malvern's NanoSight NS300 or Particle Metrix' ZetaView has not yet been conducted. To evaluate the accuracy and repeatability of size and concentration determinations of both devices, we employed comparative methods including transmission electron microscopy (TEM) and single particle interferometric reflectance imaging sensing (SP‐IRIS) by ExoView. Multiple test measurements with nanospheres, liposomes and ultracentrifuged EVs from human serum and cell culture supernatant were performed. Additionally, serial dilutions and freeze‐thaw cycle‐dependent EV decrease were measured to determine the robustness of each system. Strikingly, NanoSight NS300 exhibited a 2.0–2.1‐fold overestimation of polystyrene and silica nanosphere concentration. By measuring serial dilutions of EV samples, we demonstrated higher accuracy in concentration determination by ZetaView (% BIAS range: 2.7–8.5) in comparison with NanoSight NS300 (% BIAS range: 32.9–36.8). The concentration measurements by ZetaView were also more precise (% CV range: 0.0–4.7) than measurements by NanoSight NS300 (% CV range: 5.4–10.7). On the contrary, quantitative TEM imaging indicated more accurate EV sizing by NanoSight NS300 (% DTEM range: 79.5–134.3) compared to ZetaView (% DTEM range: 111.8–205.7), while being equally repeatable (NanoSight NS300% CV range: 0.8–6.7; ZetaView: 1.4–7.8). However, both devices failed to report a peak EV diameter below 60 nm compared to TEM and SP‐IRIS. Taken together, NTA devices differ strongly in their hardware and software affecting measuring results. ZetaView provided a more accurate and repeatable depiction of EV concentration, whereas NanoSight NS300 supplied size measurements of higher resolution.
Visuotactile synchrony of stimulation-induced sensation and natural somatosensation
Authors: Christie Breanne P , Graczyk Emily L , Charkhkar Hamid , Tyler Dustin J , Triolo Ronald J
Published: April 2019

Objective. Previous studies suggest that somatosensory feedback has the potential to improve the functional performance of prostheses, reduce phantom pain, and enhance embodiment of sensory-enabled prosthetic devices. To maximize such benefits for amputees, the temporal properties of the sensory feedback must resemble those of natural somatosensation in an intact limb. Approach. To better understand temporal perception of artificial sensation, we characterized the perception of visuotactile synchrony for tactile perception restored via peripheral nerve stimulation. We electrically activated nerves in the residual limbs of two trans-tibial amputees and two trans-radial amputees via non-penetrating nerve cuff electrodes, which elicited sensations referred to the missing limbs. Main results. Our findings suggest that with respect to vision, stimulation-induced sensation has a point of subjective simultaneity (PSS; processing time) and just noticeable difference (JND; temporal sensitivity) that are similar to natural touch. The JND was not significantly different between the participants with upper- and lower-limb amputations. However, the PSS indicated that sensations evoked in the missing leg must occur significantly earlier than those in the hand to be perceived as maximally synchronous with vision. Furthermore, we examined visuotactile synchrony in the context of a functional task during which stimulation was triggered by pressure applied to the prosthesis. Stimulation-induced sensation could be delayed up to 111  ±  62 ms without the delay being reliably detected. Significance. The quantitative temporal properties of stimulation-induced perception were previously unknown and will contribute to design specifications for future sensory neuroprostheses.
Protein multiple alignments: sequence-based versus structure-based programs
Authors: Carpentier Mathilde , Chomilier Jacques
Published: April 2019

Motivation

Multiple sequence alignment programs have proved to be very useful and have already been evaluated in the literature yet not alignment programs based on structure or both sequence and structure. In the present article we wish to evaluate the added value provided through considering structures.

Results

We compared the multiple alignments resulting from 25 programs either based on sequence, structure or both, to reference alignments deposited in five databases (BALIBASE 2 and 3, HOMSTRAD, OXBENCH and SISYPHUS). On the whole, the structure-based methods compute more reliable alignments than the sequence-based ones, and even than the sequence+structure-based programs whatever the databases. Two programs lead, MAMMOTH and MATRAS, nevertheless the performances of MUSTANG, MATT, 3DCOMB, TCOFFEE+TM_ALIGN and TCOFFEE+SAP are better for some alignments. The advantage of structure-based methods increases at low levels of sequence identity, or for residues in regular secondary structures or buried ones. Concerning gap management, sequence-based programs set less gaps than structure-based programs. Concerning the databases, the alignments of the manually built databases are more challenging for the programs.

Availability and implementation

All data and results presented in this study are available at: http://wwwabi.snv.jussieu.fr/people/mathilde/download/AliMulComp/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Functional Parcellation of Human Brain Precuneus Using Density-Based Clustering
Authors: Luo Zhiguo , Zeng Ling-Li , Qin Jian , Hou Chenping , Shen Hui , Hu Dewen
Published: April 2019

The human precuneus is involved in many high-level cognitive functions, which strongly suggests the existence of biologically meaningful subdivisions. However, the functional parcellation of the precuneus needs much to be investigated. In this study, we developed an eigen clustering (EIC) approach for the parcellation using precuneus–cortical functional connectivity from fMRI data of the Human Connectome Project. The EIC approach is robust to noise and can automatically determine the cluster number. It is consistently demonstrated that the human precuneus can be subdivided into six symmetrical and connected parcels. The anterior and posterior precuneus participate in sensorimotor and visual functions, respectively. The central precuneus with four subregions indicates a media role in the interaction of the default mode, dorsal attention, and frontoparietal control networks. The EIC-based functional parcellation is free of the spatial distance constraint and is more functionally coherent than parcellation using typical clustering algorithms. The precuneus subregions had high accordance with cortical morphology and revealed good functional segregation and integration characteristics in functional task-evoked activations. This study may shed new light on the human precuneus function at a delicate level and offer an alternative scheme for human brain parcellation.
The Democratic Case for a Written Constitution
Authors: King Jeff
Published: April 2019

Written constitutions have often been viewed as a bridle for unchecked political majoritarianism, as a restraint on government, and hence as a limiting device rather than form of democratic political expression. Breaking with that tradition, this article sets out a democratic case for a written constitution and contrasts it with the rights-based and clarity-based cases. It then proceeds to show why the case against written constitutions – which is broadly located in a conservative critique, an anti-rationalist critique and an anti-judicialisation critique – is misguided. Nevertheless, a democratic case for a written constitution necessarily raises challenging questions about how the constitution would be enacted, and how rigidly entrenched it should be. In relation to the former, the author argues for a constituent assembly consisting of party and direct citizen representation. As for the latter, he defends a model of entrenchment that permits amendment through a simple majoritarian parliamentary procedure in conjunction with a referendum, and, most controversially, a provision requiring a new constitutional convention about once in a generation. This is the type of democratic constitution, in the author’s view, that accommodates the need for the United Kingdom constitutional order to take both rights and democracy seriously.
The polarity protein Scrib limits atherosclerosis development in mice
Authors: Schürmann Christoph , Dienst Franziska L , Pálfi Katalin , Vasconez Andrea E , Oo James A , Wang ShengPeng , Buchmann Giulia K , Offermanns Stefan , van de Sluis Bart , Leisegang Matthias S , Günther Stefan , Humbert Patrick O , Lee Eunjee , Zhu Jun , Weigert Andreas , Mathoor Praveen , Wittig Ilka , Kruse Christoph , Brandes Ralf P
Published: April 2019

Aims

The protein Scrib (Scribble 1) is known to control apico-basal polarity in epithelial cells. The role of polarity proteins in the vascular system remains poorly characterized; however, we previously reported that Scrib maintains the endothelial phenotype and directed migration. On this basis, we hypothesized that Scrib has anti-atherosclerotic functions.

Methods and results

Tamoxifen-induced Scrib-knockout mice were crossed with ApoE−/− knockout mice and spontaneous atherosclerosis under high-fat diet (HFD), as well as accelerated atherosclerosis in response to partial carotid artery ligation and HFD, was induced. Deletion of Scrib resulted in increased atherosclerosis development in both models. Mechanistically, flow- as well as acetylcholine-induced endothelium-dependent relaxation and AKT phosphorylation was reduced by deletion of Scrib, whereas vascular permeability and leucocyte extravasation were increased after Scrib knockout. Scrib immune pull down in primary carotid endothelial cells and mass spectrometry identified Arhgef7 (Rho Guanine Nucleotide Exchange Factor 7, βPix) as interaction partner. Scrib or Arhgef7 down-regulation by siRNA reduced the endothelial barrier function in human umbilical vein endothelial cells. Gene expression analysis from murine samples and from human biobank material of carotid endarterectomies indicated that loss of Scrib resulted in endothelial dedifferentiation with a decreased expression of endothelial signature genes.

Conclusions

By maintaining a quiescent endothelial phenotype, the polarity protein Scrib elicits anti-atherosclerotic functions.
The Sources of Growth in a Technologically Progressive Economy: The United States, 1899–1941
Authors: Bakker Gerben , Crafts Nicholas , Woltjer Pieter
Published: April 2019

We develop new aggregate total factor productivity (TFP) growth estimates for the USA between 1899 and 1941, and sectoral estimates at the most disaggregated level so far, 38 industries. We include hard-to-measure services, and a refined measure of sectoral labour quality growth. The resulting data set supersedes Kendrick (1961), showing TFP growth lower than previously thought, broadly based across industries, and strongly variant intertemporally. The four ‘great inventions’ that Gordon (2016) highlighted were important but less dominant in TFP growth than their predecessors in the British industrial revolution. The findings also make it unlikely the 1930s had the twentieth century's highest TFP growth.
Determinants of non-participation in colon examination following positive stool sample in colorectal cancer screening
Authors: Deding Ulrik , Henig Anna Sharon , Hindersson Peter , Torp-Pedersen Christian , Bøggild Henrik
Published: April 2019

Background

Social inequalities has been shown for participation in colorectal cancer screening and recently in the initial stool sample blood test. If these differences persist at follow-up colon examination after a positive stool test, it would suggest that social inequality in screening may be greater than the inequality observed in initial stool sample blood test.

Methods

All data were derived from national registers. Using logistic regression analyses, odds of non-participation for follow-up colon examination were estimated based on age group, educational level, income quartile, immigration status and marital status in men and in women, who had participated in initial stool sample test for blood with a positive result.

Results

Among 20 849 men and 16 565 women invited for follow-up colonoscopy in the period 2014–15, 10.63 and 11.37%, respectively, did not attend. In men, odds of non-participation were higher in the eldest, those with lower income and lower educational level, in immigrants and in singles. Odds ratio (OR) in males of highest income quartile was 0.54 [95% confidence interval (CI) 0.46; 0.63] compared with lowest income quartile. In women, the differences were not as large. OR in females of highest income quartile was 0.73 (95% CI 0.61; 0.87) compared with lowest income quartile.

Conclusion

Sociodemographic differences in odds of non-participation exist in follow-up colon examination in the Danish colorectal cancer screening. Differences were evident in all subgroups of the male population. The same patterns were seen in women. Social inequalities in participation for follow-up colon examination can increase overall social inequality and consequently, lead to health disparities.
China vs the WHO: a behavioural norm conflict in the SARS crisis
Authors: Kreuder-Sonnen Christian
Published: April 2019

This article studies a conflict over two competing norms in which the actors demonstrated incompatible positions not through arguments, but through actions. During the SARS crisis, China and the World Health Organization (WHO) entered a norm conflict over the precedence of sovereignty or global health security. Both resorted to behavioural, not discursive contestation: while the WHO practically but not rhetorically challenged the sovereignty norm by acting according to the norm of global health security, China—without openly acknowledging it—contravened the basic principles of global health security by acting according to the overlapping sovereignty norm. Why and with what consequences do actors choose to contest norms through actions rather than words? The article accounts for the resort to behavioural contestation by pointing to the strategic advantages it offers for furthering a contentious norm understanding without facing the social costs of making it explicit. It furthermore highlights that behavioural contestation may feed back into and change the odds of discursive contestation as its practical effects provide rhetorical resources to (de-)legitimate one or the other position. The propositions are illustrated in the interactions of China and the WHO during the SARS crisis and the subsequent norm development. This article forms part of the special section of the May 2019 issue of International Affairs on ‘The dynamics of dissent’, guest-edited by Anette Stimmer and Lea Wisken.
Farmer monitoring reveals the effect of tidal height on mortality risk of oysters during a herpesvirus outbreak
Authors: Pernet Fabrice , Gachelin Sonia , Stanisière Jean-Yves , Petton Bruno , Fleury Elodie , Mazurié Joseph
Published: April 2019

The intertidal zone is characterized by a sharp vertical gradient of environmental stress, which structures species distribution and their interactions. Few studies, however, have examined the influence of tidal height on host–pathogen interactions. Here, we investigated how the tidal height influence outbreak of the Ostreid herpesvirus type 1 (OsHV-1) affecting the Pacific oyster. A volunteer network composed of 20 oyster growers monitored the survival of 28 batches of oysters during an epizootic event in Southern Brittany, France. Oysters were spat from wild collection or hatchery production. The sampling sites were spread over a 150-km2 area with a tidal height ranging from 0.98 to 2.90 m. Concomitantly, we followed survival of oyster spats in relation with OsHV-1 DNA detection at two sites and conducted risk analysis. We found that tidal height was associated with a lower risk of mortality. This effect was higher for hatchery than for wild oysters probably reflecting differences in health status. Our study opens perspectives for mitigation strategies based on tidal height and emphasizes the value of volunteer science in marine epidemiological studies.
Redo aortic root repair in patients with infective prosthetic endocarditis using xenopericardial solutions
Authors: Kondov Stoyan , Beyersdorf Friedhelm , Rylski Bartosz , Kreibich Maximilian , Dimov Aleksandar , Berger Tim , Siepe Matthias , Czerny Martin
Published: April 2019

OBJECTIVES

We describe a conceptual approach involving the use of self-made xenopericardial grafts in combination with biological aortic valve prostheses and in addition using a xenopericardial tubes for aortic valve reimplantation in patients with infective prosthetic endocarditis after aortic root repair or supracoronary ascending aortic replacement.

METHODS

The cohort comprised 7 consecutive patients with proven prosthetic infection either after aortic root replacement (n = 5), the David operation (n = 1) or supracoronary ascending aortic replacement (n = 1). The strategy consists of complete removal of the infected prosthetic material and orthotopic reconstruction using a bovine pericardial patch sewn as a tube according to the required aortic diameter.

RESULTS

In case of valve replacement, Edwards Magna Ease (n = 4 patients) and Edwards Inspiris (n = 2 patients) were used inside the xenopericardial tube. Five patients also required hemiarch and 1 patient required complete aortic arch replacement. Median length of stay in the intensive care unit and on the regular ward thereafter was 11 (6.5–13.5) days and 26.0 (14.5–32.5) days, respectively. All patients were successfully discharged. Median follow-up time was 7.6 (±2.1) months. Currently, all patients are not on antibiotic therapy and free from any signs of persisting or recurring infection. At the short-term follow-up, no structural valve deterioration, paravalvular insufficiency or graft calcification was found.

CONCLUSIONS

Using a self-made xenopericardial graft in combination with a biological aortic valve prosthesis for a Bio-Bentall and using a xenopericardial tube for a Bio-David operation is a safe and reproducible strategy and presents an off-the-shelf alternative to homografts. The short-term results of this approach are excellent. Further studies are needed to confirm mid- and long-term durability in larger cohorts.
The impact of violence on Venezuelan life expectancy and lifespan inequality
Authors: García Jenny , Aburto José Manuel
Published: April 2019

Background

Venezuela is one of the most violent countries in the world. According to the United Nations, homicide rates in the country increased from 32.9 to 61.9 per 100 000 people between 2000 and 2014. This upsurge coincided with a slowdown in life expectancy improvements. We estimate mortality trends and quantify the impact of violence-related deaths and other causes of death on life expectancy and lifespan inequality in Venezuela.

Methods

Life tables were computed with corrected age-specific mortality rates from 1996 to 2013. From these, changes in life expectancy and lifespan inequality were decomposed by age and cause of death using a continuous-change model. Lifespan inequality, or variation in age at death, is measured by the standard deviation of the age-at-death distribution.

Results

From 1996 to 2013 in Venezuela, female life expectancy rose 3.57 [95% confidence interval (CI): 3.08–4.09] years [from 75.79 (75.98–76.10) to 79.36 (78.97–79.68)], and lifespan inequality fell 1.03 (–2.96 to 1.26) years [from 18.44 (18.01–19.00) to 17.41 (17.30–18.27)]. Male life expectancy increased 1.64 (1.09–2.25) years [from 69.36 (68.89–59.70) to 71.00 (70.53–71.39)], but lifespan inequality increased 0.95 (–0.80 to 2.89) years [from 20.70 (20.24–21.08) to 21.65 (21.34–22.12)]. If violence-related death rates had not risen over this period, male life expectancy would have increased an additional 1.55 years, and lifespan inequality would have declined slightly (–0.31 years).

Conclusions

As increases in violence-related deaths among young men (ages 15–39) have slowed gains in male life expectancy and increased lifespan inequality, Venezuelan males face more uncertainty about their age at death. There is an urgent need for more accurate mortality estimates in Venezuela.