bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic study of temperature and density variations in effective potentials for coarse-grained models of molecular liquids
Authors: Lebold Kathryn M. , Noid W. G.
Published: January 2019

Due to their computational efficiency, coarse-grained (CG) models are widely adopted for modeling soft materials. As a consequence of averaging over atomistic details, the effective potentials that govern the CG degrees of freedom vary with temperature and density. This state-point dependence not only limits their range of validity but also presents difficulties when modeling thermodynamic properties. In this work, we systematically examine the temperature- and density-dependence of effective potentials for 1-site CG models of liquid ethane and liquid methanol. We employ force-matching and self-consistent pressure-matching to determine pair potentials and volume potentials, respectively, that accurately approximate the many-body potential of mean force (PMF) at a range of temperatures and densities. The resulting CG models quite accurately reproduce the pair structure, pressure, and compressibility of the corresponding all-atom models at each state point for which they have been parameterized. The calculated pair potentials vary quite linearly with temperature and density over the range of liquid state points near atmospheric pressure. These pair potentials become increasingly repulsive both with increasing temperature at constant density and also with increasing density at constant temperature. Interestingly, the density-dependence appears to dominate, as the pair potentials become increasingly attractive with increasing temperature at constant pressure. The calculated volume potentials determine an average pressure correction that also varies linearly with temperature, although the associated compressibility correction does not. The observed linearity allows for predictions of pair and volume potentials that quite accurately model these liquids in both the constant NVT and constant NPT ensembles across a fairly wide range of temperatures and densities. More generally, for a given CG configuration and density, the PMF will vary linearly with temperature over the temperature range for which the entropy associated with the conditioned distribution of atomic configurations remains constant.
Pressure dependence of singly and doubly charged ion formation in a HiPIMS discharge
Authors: Hippler R. , Cada M. , Stranak V. , Helm C. A. , Hubicka Z.
Published: January 2019

Generation of singly charged Ar+ and Ti+, doubly charged Ar2+ and Ti2+, and of Ar2+ and Ti2+ dimer ions in a high power impulse magnetron sputtering (HiPIMS) discharge with a Ti cathode was investigated. Energy-resolved mass spectrometry was employed. The argon gas pressures varied between 0.5 and 2.0 Pa. Energy spectra of monomer ions are composed of low- and high-energy components. The energetic position of the high-energy component is approximately twice as large for doubly charged ions compared to singly charged ions. Intensities of Ar2+ and Ti2+ dimer ions are considerably smaller during HiPIMS compared to dc magnetron sputtering.
Bias dependent conductance in CoFeB-MgO-CoFeB magnetic tunnel junctions as an indicator for electrode magnetic condition at barrier interfaces
Authors: Sun J. Z. , Trouilloud P. L. , Lauer G. P. , Hashemi P.
Published: January 2019

Barrier interface condition is critical for spin-polarized tunneling and spin-transfer torque switching in CoFeB∣MgO∣CoFeB-based magnetic tunnel junctions. The differential tunnel conductance gV contains information on CoFeB’s magnetic properties at tunnel interfaces. Experimentally, we find gV to follow a “cross-normalization” relationship between the parallel and antiparallel alignments. This we show originates from the leading order spin-flip scatter terms related to CoFeB interface magnetic properties such as its exchange-stiffness. By connecting the observable gV slopes to electrode-specific spin-flip scatter rates, we obtain an efficient measurement for mass-screening of junctions for interface magnetic differences. This provides valuable information for device and fabrication process optimization.
Carrier localization structure combined with current micropaths in AlGaN quantum wells grown on an AlN template with macrosteps
Authors: Kojima K. , Nagasawa Y. , Hirano A. , Ippommatsu M. , Honda Y. , Amano H. , Akasaki I. , Chichibu S. F.
Published: January 2019

The microscopic structural and optical characteristics of AlGaN-based light-emitting diodes grown on AlN templates with macrosteps were evaluated. Cross-sectional transmission electron microscopy in the high-angle annular dark field scanning mode and microscopic energy dispersive X-ray spectroscopy reveal that the AlGaN cladding layer under the AlGaN quantum wells (QWs) has microscopic compositional modulations originating from the macrosteps at the AlN template surface. The Ga-rich oblique zones in the cladding layer likely behave as current micropaths. These micropaths are connected to the carrier localization structure, which is formed by the modulation of both the well widths and the compositions of the QWs. In-plane spatially-resolved cathodoluminescence (CL) spectroscopy indicated significant inhomogeneity of the CL characteristics: the brighter emission with a lower peak photon energy confirms the existence of the carrier localization structure in the QWs. Carrier localization in the QWs along with the current micropaths in the AlGaN cladding layer appears to increase the external quantum efficiency of AlGaN LEDs.
Why does NiOOH cocatalyst increase the oxygen evolution activity of α-Fe2O3?
Authors: George Kiran , Zhang Xueqing , Bieberle-Hütter Anja
Published: January 2019

Nickel oxyhydroxide (NiOOH) is known to increase the oxygen evolution reaction (OER) performance of hematite (Fe2O3) photoanodes. In recent experimental studies, it has been reported that the increased OER activity is related to the activation of the hematite (α-Fe2O3) surface by NiOOH rather than the activity of NiOOH itself. In this study, we investigate the reason behind the higher activity and the low overpotentials for NiOOH-Fe2O3 photoanodes using first principles calculations. To study the activity of possible catalytic sites, different geometries with NiOOH as a cluster and as a strip geometry on hematite (110) surfaces are studied. Density functional theory + U calculations are carried out to determine the OER activity at different sites of these structures. The geometry with a continuous strip of NiOOH on hematite is stable and is able to explain the activity. We found that the Ni atoms at the edge sites of the NiOOH cocatalyst are catalytically more active than Ni atoms on the basal plane of the cocatalyst; the calculated overpotentials are as low as 0.39 V.
Direct measurements of steady heat transfer maintained by oscillating pipe flow in thermoacoustic system
Authors: Biwa T. , Kobayashi T. , Hyodo H.
Published: January 2019

This study reports direct measurements of steady heat transfer in a heat exchanger pipe of a thermoacoustic heat pump driven by an oscillating helium gas flow. From simultaneous measurements of gas temperature, pressure, and velocity fluctuations, the steady heat transfer rate is determined from the radial profile of the temporal mean temperature and from the axial distribution of the enthalpy flux density. The heat transfer coefficient h is determined to be given by h=2k/r0 consistently in the range of 1.6≤r0/δα≤6.6, where k is the gas thermal conductivity, r0 is the tube radius, and δα=2α/ω is the characteristic transverse length given by using the thermal diffusivity and angular frequency.
Superimposed-harmonic Smith-Purcell free-electron lasers driven by periodic electron-bunches
Authors: Liang Linbo , Liu Weihao , Jia Qika , Wang Lin , Lu Yalin
Published: January 2019

To meet the requirements of high power and broad-tunable terahertz sources, we proposed and investigated a modified Smith-Purcell free-electron laser (SP-FEL) driven by periodic electron-bunches (PEBs). We first designed an electron-gun with a photocathode, which generates a train of PEBs with tunable macro-bunching frequency. These PEBs then interact with surface waves on a grating and are further micro-bunched. The macro-bunching frequency together with its harmonics is superimposed on the micro-bunching one such that the multi-color superradiant Smith-Purcell radiation is achieved at the superimposed harmonics. By adjusting the macro-bunching frequency, the superradiant frequency can be tuned from 0.5 to 1 THz—a region hard to reach by conventional SP-FELs and vacuum electron devices. Compared to DC-beams, the PEBs have higher peak current density and generate higher peak power. Thus, the proposed scheme can be promisingly developed as high power and broad-tunable terahertz sources.
Barley yellow dwarf virus infection affects physiology, morphology, grain yield and flour pasting properties of wheat
Authors: Choudhury Shormin , Larkin Philip , Meinke Holger , Hasanuzzaman M. D. , Johnson Peter , Zhou Meixue
Published: January 2019

Barley yellow dwarf virus (BYDV) is a phloem-limited virus that is persistently transmitted by aphids and causes significant yield losses in wheat (Triticum aestivum L.). The present study was conducted to investigate the effects of BYDV in wheat on physiological and morphological traits, yield attributes and pasting properties of flour, and to determine any differences for these traits between susceptible and resistant genotypes under BYDV infection. Significant impact on physiological and morphological traits and yield was observed in plants inoculated at the 2-leaf stage (Zadoks scale, Z12), with a greater impact in the three susceptible genotypes than in the resistant genotype. Yield reduction with inoculation at Z12 was 18–49%, and yield reduction with inoculation mid tillering (Z25) was 6–31%. There was a significant reduction in effective tiller number with both inoculation times, but 1000-kernel weight was affected only with early inoculation. Pasting properties were little affected by BYDV infection, with genotype having a larger effect than infection. Grain yield showed negative correlation with tissue-blot immunoassay and visual symptom score, and positive correlation with all gas-exchange parameters, chlorophyll fluorescence, leaf area and biomass weight. The results suggest that stomatal conductance, transpiration rate and chlorophyll fluorescence measurements are suitable for assessment of BYDV infection and for screening BYDV of susceptible and resistant wheat genotypes.
Personal and reported partner pornography viewing by Australian women, and association with mental health and body image
Authors: Laemmle-Ruff Ingrid L. , Raggatt Michelle , Wright Cassandra J. C. , Carrotte Elise R. , Davis Angela , Jenkinson Rebecca , Lim Megan S. C.
Published: January 2019

Background
Personal and partner pornography viewing may affect health and wellbeing. This study aimed to improve understanding of the effects of pornography on mental health and body image, given emerging evidence of increasing use, particularly among young people. Methods: A cross-sectional survey was implemented, targeting people who had accessed health and fitness content via social media. Convenience sampling was used and participants were recruited via advertising on social media. Results: Overall, 76% (75/99) of women reported having ever viewed pornography, and 21% had viewed pornography frequently (monthly/weekly/daily) in the prior 12 months. The association between frequent viewing and higher-risk Kessler 10 Psychological Distress Scale scores lost significance once controlled for age (adjusted OR 2.30, 95%CI 0.82–6.49, P=0.11). There was an association with frequent reported partner pornography use (monthly/weekly/daily) and increased Drive for Muscularity scores (adjusted OR 2.20, 95%CI 1.01–4.80, P=0.048). There were no other associations found with pornography use (personal or partner) and body image or mental health, although this was limited by the small sample size. Most women (85%, 41/48) reported being happy with their partner’s pornography use, and in qualitative responses, indicated that pornography had minimal effect on their lives. Nevertheless, multiple qualitative responses indicated a multiplicity of perceived effects of pornography, including negative effects on body image. Conclusions: Pornography had a minor effect on mental health and body image in this study. Additional research is required to improve understanding of the effects of pornography on body image and mental health, particularly among vulnerable individuals.
The failure of planning to address the urban interface and intermix fire-hazard problems in the San Francisco Bay Area
Authors: McBride Joe R. , Kent Jerry
Published: January 2019

Post-fire planning following major fires in the San Francisco Bay area has identified problems of wildland fuel management and solutions to these problems; however, the failure to carry out many of the fuel management recommendations has led to increasing fire hazard for the urban interface and urban intermix zones. A proposal for a new state agency to oversee fuel management is presented.
Effects of the interpreter’s political awareness on pronoun shifts in political interviews
Authors: Guo Yijun
Published: January 2019

This paper investigates the critical role of the interpreter’s political awareness in interpreting high-level political interviews in China, and its effects on pronoun shifts. Using former Chinese Premier Zhu’s debut press conference in 1998 as a case study, the study examines in detail the pronoun shifts of a China’s Foreign Ministry senior interpreter prompted by her political awareness. It identifies four types of pronoun shifts: (1) from first-person singular pronoun (“I”) to first-person plural pronoun (“we”); (2) from active voice with first-person plural pronoun as subject to passive voice; (3) from pronoun to a third-party noun; and (4) replacement of a noun with an interactant pronoun. The paper considers implications of these findings in relation to relevant studies and to the macro-social institutional context in which the political interpreting is conducted. The paper argues that this type of political awareness is a form of socio-institutional cognition inculcated and developed through the interpreter’s diplomatic identity, their understanding of socio-institutional requirements, strict training and a large quantity of supervised practice.
Maximal lexicographic spectra and ranks for states with fixed uniform margins
Authors: Li Xin
Published: January 2019

We find the spectrum in maximal lexicographic order for quantum states

ρ

A
B

∈

H

A

⊗

H

B

\rho _{AB}\in \mathcal {H}_A\otimes \mathcal {H}_B

with margins

ρ
A

=

1
n

I
n

\rho _A=\frac {1}{n}I_n

and

ρ
B

=

1
m

I
m

\rho _B=\frac {1}{m}I_m

and discuss the construction of

ρ

A
B

\rho _{AB}

. By nonzero rectangular Kronecker coefficients, we give counterexamples for Klyachko’s conjecture which says that a quantum state with maximal lexicographical spectrum has minimal rank among all states with given margins. Moreover, we show that quantum states with the maximal lexicographical spectrum are extreme points.
Does Coinoculation with Different Verticillium dahliae Genotypes Affect the Host or Fungus?
Authors: Wheeler David Linnard , Johnson Dennis Allen
Published: January 2019

Inferences about Verticillium dahliae are often deduced from experiments where hosts are inoculated with one isolate. The assumption that the outcomes from these experiments scale with V. dahliae diversity is untested. The objectives of this research were to test the hypotheses that (i) coinoculation with combinations of isolates affects plant biomass, disease expression, and fungal colonization; and (ii) hosts select for the specific isolates. Potato, mustard, and barley plants were coinoculated with seven combinations of three isolates. Genotypes recovered from infected plants were genotyped with microsatellite markers. Disease expression and fungal colonization but not plant biomass of potato was affected by coinoculation (F = 7.07, P < 0.0001; F = 2.36, P = 0.0427) and depended on the isolates with which plants were inoculated. One genotype was disproportionately selected for by all hosts. Putative heterokaryons were recovered from mustard plants coinoculated with isolates of different vegetative compatibility groups (VCG). These results support the assumption that mixed infections have marginal impacts on plant biomass but challenge the assumption that they do not affect disease expression and fungal colonization. Finally, this research provides evidence that plants select for specific V. dahliae genotypes and isolates from different VCGs can anastomose in planta.
Surgical management of Gartland type III supracondylar humerus fractures in older children: a retrospective study
Authors: Li Mingjing , Xu Jian , Hu Tao , Zhang Ming , Li Fan
Published: January 2019

The aim of this study was to analyse the management of Gartland type III supracondylar humerus fractures in children older than 10 years at our paediatric orthopaedics and to determine the clinical and radiographic long-term effects following open reduction by the small medial approach and cross-fixation with three kirschner wires. Eighty-three cases of Gartland type III supracondylar humerus fractures in children older than 10 years were treated by open reduction by the small medial approach and cross-fixation with three kirschner wires from January 2010 to December 2015. All patients were followed up from 12 to 15 months (mean: 13 months). Assessments after 1 year included neurovascular examination, Flynn’s criteria (elbow function and carrying angle), pain and complications (infections, growth disturbances or iatrogenic nerve injuries). All fractures healed within 2 months. According to Flynn’s criteria, 80 (96.4%) patients achieved satisfactory outcomes, whereas three (3.6%) were graded as unsatisfactory because of limited elbow motion. The mean carrying angle measured 9.4° (1°–16°) compared with 10.8° on the contralateral side (5°–16°). No case of cubitus varus was noted. No wound infection and displacement of bone fracture occurred. No case of iatrogenic ulnar nerve injury and vascular deficits was noted. There were no cases of myositis ossificans or Volkmann’s ischaemic contracture. It is safe and effective to treat Gartland type III paediatric supracondylar humerus fractures in older children with open reduction by the medial approach and crossed K-wires fixation.
Posttraumatic Stress Disorder in the Primary Care Setting: Summary of Recommended Care
Authors: Spottswood Margaret , Fortney John , Chen Jessica A. , Davydow Dimitry , Huang Hsiang
Published: January 2019

Posttraumatic stress disorder (PTSD) occurs following acute threatening events in approximately 12.5% of the primary care population.

Objective

The aim of this article is to advance evidence-based clinical practice and collaborative care approaches to PTSD by summarizing targeted-care guidelines.

Method

This narrative literature review addresses important aspects of PTSD and management options, in conjunction with expert opinion when indicated. Guidelines were included if they targeted treatment of PTSD in the primary care setting or if the treatments described could be provided in the primary care setting.

Results

The implications regarding PTSD, comorbidities, differential diagnosis, screening tools, and treatment are presented.

Conclusion

Primary care providers can diagnose and offer initial management of PTSD. Future research should delineate therapies helpful for complex PTSD, including group therapies, those increasing self-compassion, and other optimally effective collaborative care interventions.
Prognostic value of international normalized ratio to albumin ratio among critically ill patients with cirrhosis
Authors: Gao Feng , Cai Meng-Xing , Lin Miao-Tong , Xie Wei , Zhang Ling-Zhi , Ruan Qian-Zi , Huang Zhi-Ming
Published: January 2019

Background and aim

Critically ill patients with cirrhosis are at an increased risk of mortality. Our study aimed to externally validate the ability of the prothrombin time–international normalized ratio to albumin ratio (PTAR), an objective and simple scoring system, to predict 90-day mortality in critically ill patients with cirrhosis.

Patients and methods

A total of 865 patients were entered into the study, and all the participants were followed up for at least 90 days. Clinical parameters on the first day of intensive care unit admission were included to compare survivors with nonsurvivors.

Results

After multivariable adjustment, the association between the risk of 90-day mortality and PTAR remained statistically significant with a hazard ratio of 2.71 (95% confidence interval: 1.99–3.68). The PTAR score showed good discrimination ability for predicting 90-day mortality with an area under receiver operating characteristic curve of 0.72 (95% confidence interval: 0.68–0.75). To improve its feasibility, we regrouped the PTAR scores into three levels of risk (low risk: <0.55, intermediate risk: 0.55–1.00, and high risk: ≥1.00); the 90-day mortality rates were 20.1% (74/368), 41.7% (168/403), and 73.4% (69/94), respectively.

Conclusion

The PTAR score system is a convenient and practical tool for predicting the prognosis of critically ill patients with cirrhosis.
Competing risks and cause-specific mortality in patients with pancreatic neuroendocrine tumors
Authors: Li Zhuyin , Du Shuai , Feng Wei , Zhang Weibo , Li Guochuang , Wei Junfeng , Zhang Guoqing , Zhao Longshuan
Published: January 2019

Background and objective

Currently, there are no competing risk analyses of cause-specific mortality in patients with pancreatic neuroendocrine tumors.

Materials and methods

We estimated a cumulative incidence function for cause-specific mortality. The first nomogram for predicting cause-specific mortality was constructed using a proportional subdistribution hazard model, validated using bootstrap cross-validation, and evaluated with decision curve analysis.

Results

Sex, age, positive lymph node status, metastasis, surveillance, epidemiology, and end results historic stage, grade, and surgery strongly predicted cause-specific mortality. The discrimination performance of Fine–Gray models was evaluated using the c-index, which was 0.864. In addition, the calibration plot of the developed nomogram demonstrated good concordance between the predicted and actual outcomes. Decision curve analysis yielded a range of threshold probabilities (0.014–0.779) at which the clinical net benefit of the risk model was greater than that in hypothetical all-screening or no-screening scenarios.

Conclusion

Our nomogram allows selection of a patient population at high risk for cancer-specific mortality and thus facilitates the design of prevention trials for the affected population.
Mafic glass compositions: a record of magma storage conditions, mixing and ascent
Authors: Cashman Katharine V. , Edmonds Marie
Published: January 2019

The trans-crustal magma system paradigm is forcing us to re-think processes responsible for magma evolution and eruption. A key concept in petrology is the liquid line of descent (LLD), which relates a series of liquids derived from a single parent, and therefore tracks the inverse of the crystallization path. It is common practice to attribute multiple magma compositions, and/or multiple melt compositions (from melt inclusions and matrix glass), to a single LLD. However, growing evidence for rapid, and often syn-eruptive, assembly of multiple magma components (crystals and melts) from different parts of a magmatic system suggests that erupted magma and melt compositions will not necessarily represent a single LLD, but instead may reflect the multiple paths in pressure–temperature space. Here, we use examples from mafic magmatic systems in both ocean island and arc settings to illustrate the range of melt compositions present in erupted samples, and to explore how they are generated, and how they interact. We highlight processes that may be deduced from mafic melt compositions, including the mixing of heterogeneous primitive liquids from the mantle, pre-eruptive magma storage at a range of crustal and sub-Moho depths, and syn-eruptive mixing of melts generated from these storage regions. The relative dominance of these signatures in the glasses depends largely on the water content of the melts. We conclude that preserved melt compositions provide information that is complementary to that recorded by the volatile contents of crystal-hosted melt inclusions and coexisting mineral compositions, which together can be used to address questions about both the pre- and syn-eruptive state of volcanic systems.

This article is part of the Theo Murphy meeting issue ‘Magma reservoir architecture and dynamics’.
Thoughts on the criteria to determine the origin of volcanic unrest as magmatic or non-magmatic
Authors: Pritchard M. E. , Mather T. A. , McNutt S. R. , Delgado F. J. , Reath K.
Published: January 2019

As our ability to detect volcanic unrest improves, we are increasingly confronted with the question of whether the unrest has a magmatic origin (magma on the move) or a non-magmatic origin from a change in the hydrothermal system (fluids that are not magma on the move) or tectonic processes. The cause of unrest has critical implications for the potential eruptive hazard (e.g. used in constructing Bayesian Event Trees), but is frequently the subject of debate, even at well-studied systems. Here, we propose a set of multi-disciplinary observations and numerical models that could be used to evaluate conceptual models about the cause of unrest. These include measurements of gas fluxes and compositions and the isotopic signature of some components (e.g. H2, He, C, SO2, H2O, CH4and CO2), the spatial and temporal characteristics of ground deformation, thermal output, seismicity, changes in gravity, and whether there is topographic uplift or subsidence spanning hundreds to thousands of years. In several volcanic systems, both magmatic and non-magmatic unrest is occurring at the same time. While none of these observations or models is diagnostic on its own, we illustrate several examples where they have been used together to make a plausible conceptual model of one or more episodes of unrest and whether eruptions did or did not follow the unrest.

This article is part of the Theo Murphy meeting issue ‘Magma reservoir architecture and dynamics’.
Time scales and temperatures of crystal storage in magma reservoirs: implications for magma reservoir dynamics
Authors: Cooper Kari M.
Published: January 2019

The thermal and therefore physical state of magma bodies within the crust controls the processes and time scales required to mobilize magmas before eruptions, which in turn are critical to hazard assessment. Crystal records can be used to reconstruct magma reservoir histories, and the resulting time and length scales are converging with those accessible through numerical modelling of magma system dynamics. The goal of this contribution is to summarize constraints derived from crystal chronometry (radiometric dating and modelling intracrystalline diffusion durations), in order to facilitate use of these data by researchers in other fields. Crystallization ages of volcanic minerals typically span a large range (10
4
–10
5
 years), recording protracted activity in a given magma reservoir. However, diffusion durations are orders of magnitude shorter, indicating that the final mixing and assembly of erupted magma bodies is rapid. Combining both types of data in the same samples indicates that crystals are dominantly stored at near- or sub-solidus conditions, and are remobilized rapidly prior to eruptions. These observations are difficult to reconcile with some older numerical models of magma reservoir dynamics. However, combining the crystal-scale observations with models which explicitly incorporate grain-scale physics holds great potential for understanding dynamics within crustal magma reservoirs.

This article is part of the Theo Murphy meeting issue ‘Magma reservoir architecture and dynamics’.
Consequences of a crystal mush-dominated magma plumbing system: a mid-ocean ridge perspective
Authors: Lissenberg C. Johan , MacLeod Christopher J. , Bennett Emma N.
Published: January 2019

Crystal mush is rapidly emerging as a new paradigm for the evolution of igneous systems. Mid-ocean ridges provide a unique opportunity to study mush processes: geophysical data indicate that, even at the most magmatically robust fast-spreading ridges, the magma plumbing system typically comprises crystal mush. In this paper, we describe some of the consequences of crystal mush for the evolution of the mid-ocean ridge magmatic system. One of these is that melt migration by porous flow plays an important role, in addition to rapid, channelized flow. Facilitated by both buoyancy and (deformation-enhanced) compaction, porous flow leads to reactions between the mush and migrating melts. Reactions between melt and the surrounding crystal framework are also likely to occur upon emplacement of primitive melts into the mush. Furthermore, replenishment facilitates mixing between the replenishing melt and interstitial melts of the mush. Hence, crystal mushes facilitate reaction and mixing, which leads to significant homogenization, and which may account for the geochemical systematics of mid-ocean ridge basalt (MORB). A second consequence is cryptic fractionation. At mid-ocean ridges, a plagioclase framework may already have formed when clinopyroxene saturates. As a result, clinopyroxene phenocrysts are rare, despite the fact that the vast majority of MORB records clinopyroxene fractionation. Hence, melts extracted from crystal mush may show a cryptic fractionation signature. Another consequence of a mush-dominated plumbing system is that channelized flow of melts through the crystal mush leads to the occurrence of vertical magmatic fabrics in oceanic gabbros, as well as the entrainment of diverse populations of phenocrysts. Overall, we conclude that the occurrence of crystal mush has a number of fundamental implications for the behaviour and evolution of magmatic systems, and that mid-ocean ridges can serve as a useful template for trans-crustal mush columns elsewhere.

This article is part of the Theo Murphy meeting issue ‘Magma reservoir architecture and dynamics'.
Tumors escape immunosurveillance by overexpressing the proteasome activator REGγ
Authors: Boulpicante Mathilde , Darrigrand Romain , Pierson Alison , Salgues Valerie , Gaudineau Benoit , Khaled Mehdi , Cattaneo Angela , Bachi Angela , Cascio Paolo , Apcher Sébastien
Published: January 2019

The success of CD8+ T cell based cancer immunotherapy emphasizes the importance of understanding the mechanisms of generation of MHC-I peptide ligands and possible pathways of tumor cell escape from immunosurveillance. Recently, we showed that peptides generated in the nucleus during the pioneer round of mRNA translation (pioneer translation products, or PTPs) can be a potentially important source of tumor specific peptides, given the presence of aberrant splicing and transcription associated with oncogenesis. Here we show that cancer cells up-regulation of the REGγ proteasome regulator results in increased destruction of PTP-derived peptides in the nucleus thus subverting immunosurveillance. These findings add to understanding of the role of REGγ in antigen processing and identify it as a druggable target for improving the efficacy of cancer immunotherapy.

Significance

With the clear success of CD8+ T cell based immunotherapy, it is critical to understand i) how tumor cells generate MHC-I peptide antigens? and ii) the various mechanisms used by cancer cells to evade immunosurveillance. One of them is to up-regulate the REGγ proteasome regulator which results in an increase destruction of MHC-I peptides in the nucleus thus subverting immunosurveillance.
A contractile acto-myosin belt promotes growth anisotropy during the early stages of pectoral fin development in zebrafish
Authors: Kardash Elena , Nguyen Hanh , Behrndt Martin , Heisenberg Carl-Philipp , Peyriéras Nadine , Gonzalez-Gaitan Marcos
Published: January 2019

The zebrafish pectoral fin is anin vivomodel for vertebrate limb formation, well suited to investigate the integration of molecular and cellular dynamics, the results of which translate into shaping the limb bud. We used the ratio between the lengths of the anterior-posterior (AP) and dorso-ventral (DV) axes as the descriptor of how fin shape changes over time. We showed that fin shape transitions from close to hemi-spherical (ratio 1. 36 ± 0.11) to semi-ellipsoid (ratio 1.64 ± 0.04) between 33 and 46 hours post fertilization (hpf). This shape transition coincided with the formation of a contractile “actin belt” at the distal rim of the fin bud along its AP axis. The actin belt emerged from a central position and expanded on both sides along the distal rim of the fin, thus marking the DV boundary between two rows of ectodermal cells. Formation of the actin belt depended on Rac protein activity, as suggested by FRET measurements using a Rac biosensor. 3D+time imaging of the developing fin in Rac-deficient embryos showed that anisotropic growth of the fin depends on the actin belt. Indeed, actin belt formation was dramatically reduced or even absent in the embryos without proper Rac activity. This correlated with isotropic growth of the fin bud from normal shape at 33 hpf to quasi hemispherical shape with AP/DV ratio ~1 13 hours later, without affecting cell number and overall bud volume. We propose that the formation of a contractile acto-myosin belt is essential to drive the pectoral fin’s early anisotropic growth.
Protein Co-Evolution Strategies Detect Predicted Functional Interaction Between the Serotonin 5-HT2A and 5-HT2C Receptors
Authors: Fongang Bernard , Cunningham Kathryn A. , Rowicka Maga , Kudlicki Andrzej
Published: January 2019

Serotonin is a neurotransmitter that plays a role in regulating activities such as sleep, appetite, mood and substance abuse disorders; serotonin receptors 5-HT2AR and 5-HT2CR are active within pathways associated with substance abuse. It has been suggested that 5-HT2AR and 5-HT2CR may form a dimer that affects behavioral processes. Here we study the coevolution of residues in 5-HT2AR and 5-HT2CR to identify potential interactions between residues in both proteins. Coevolution studies can detect protein interactions, and since the thus uncovered interactions are subject to evolutionary pressure, they are likely functional. We assessed the significance of the 5-HT2AR/5-HT2CR interactions using randomized phylogenetic trees and found the interaction significant (p-value = 0.01). We also discuss how co-expression of the receptors suggests the predicted interaction is functional. Finally, we analyze how several single nucleotide polymorphisms for the 5-HT2AR and 5-HT2CR genes affect their interaction. Our findings are the first to characterize the binding interface of 5-HT2AR/5-HT2CR and indicate a correlation between this interface and location of SNPs in both proteins.
The gut microbiota is associated with clearance of Clostridium difficile infection independent of adaptive immunity
Authors: Leslie Jhansi L. , Vendrov Kimberly C. , Jenior Matthew L. , Young Vincent B.
Published: January 2019

Clostridium (Clostridioides) difficile, a Gram-positive, anaerobic bacterium is the leading single cause of nosocomial infections in the United States. A major risk factor for C. difficile infection (CDI) is prior exposure to antibiotics as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80-90% success rate of fecal microbial transplants in treating recurrent infection. Adaptive immunity, specifically humoral immunity, is also sufficient to protect from both acute and recurrent CDI. However, the role of the adaptive immune system in mediating clearance of C. difficile has yet to be resolved. Using murine models of CDI, we found that adaptive immunity is dispensable for clearance of C. difficile. However, Random Forest analysis using only 2 members of the resident bacterial community correctly identified animals that would go on to clear the infection with 66.7% accuracy. These findings indicate that the indigenous gut microbiota independent of adaptive immunity facilitates clearance of C. difficile from the murine gastrointestinal tract.

Importance

C. difficile infection is a major cause of morbidity and mortality in hospitalized patients in the United States. Currently the role of the adaptive immune response in modulating levels of C. difficile colonization is unresolved. This work suggests that the indigenous gut microbiota is a main factor that promotes clearance of C. difficile from the GI tract. Our results show that clearance of C. difficile can occur without contributions from the adaptive immune response. This study also has implications for the design of preclinical studies testing the efficacy of vaccines on clearance of bacterial pathogens as inherent differences in the baseline community structure of animals may bias findings.
Multilocus sequence analysis, a rapid and accurate identification tool for taxonomic classification, evolutionary relationship and population biology of the genus Shewanella
Authors: Fang Yujie , Wang Yonglu , Liu Zongdong , Dai Hang , Cai Hongyan , Li Zhenpeng , Du Zongjun , Wang Xin , Jing Huaiqi , Wei Qiang , Kan Biao , Wang Duochun
Published: January 2019

The genus Shewanella comprises a group of marine-dwelling species with worldwide distribution. Several species are regarded as causative agents of food spoilage and opportunistic pathogens of human diseases. In this study, a standard multilocus sequence analysis (MLSA) based on six protein-coding genes (gyrA, gyrB, infB, recN, rpoA and topA) was established as a rapid and accurate identification tool in fifty-nine type Shewanella strains. This method yielded sufficient resolving power in regard to enough informative sites, adequate sequence divergences and distinct interspecies branches. The stability of phylogenetic topology was supported by high bootstrap values and concordance with different methods. The reliability of the MLSA scheme was further validated by identical phylogenies and high correlations of genomes. The MLSA approach provided a robust system to exhibit evolutionary relationships in the Shewanella genus. The split network tree proposed twelve distinct monophyletic clades with identical G+C contents and high genetic similarities. Eighty-six tested strains were investigated to explore the population biology of the Shewanella genus in China. The most prevalent Shewanella species were Shewanella algae, Shewanella xiamenensis, Shewanella chilikensis, Shewanella indica, Shewanella seohaensis and Shewanella carassii. The strains frequently isolated from clinical and food samples highlighted the importance of increasing the surveillance of Shewanella species. Combined with the genetic, genomic and phenotypic analyses, Shewanella upenei should be considered a synonym of S. algae, and Shewanella pacifica should be reclassified as a synonym of Shewanella japonica.

IMPORTANCE

The MLSA scheme based on six HKGs (gyrA, gyrB, infB, recN, rpoA and topA) is well established as a reliable tool for taxonomic, evolutionary and epidemiological analyses of the genus Shewanella in this study. The standard MLSA method allows researchers to make rapid, economical and precise identification of Shewanella strains. The robust phylogenetic network of MLSA provides profound insight into the evolutionary structure of the genus Shewanella. The population genetics of Shewanella species determined by the MLSA approach plays a pivotal role in clinical diagnosis and routine monitoring. Further studies on remaining species and genomic analysis will enhance a more comprehensive understanding of the microbial systematics, phylogenetic relationships and ecological status of the genus Shewanella.
Splicing inhibition enhances the antitumor immune response through increased tumor antigen presentation and altered MHC-I immunopeptidome
Authors: Pierson Alison , Darrigrand Romain , Rouillon Marine , Boulpicante Mathilde , Renko Zafiarisoa Dolor , Garcia Camille , Ghosh Michael , Laiguillon Marie-Charlotte , Lobry Camille , Alami Mouad , Apcher Sébastien
Published: January 2019

The success of cancer immunotherapy relies on the induction of an immunoprotective response targeting tumor antigens (TAs) presented by tumor cells on MHC class I molecules. Alternative translation events emerged as a rich source of TAs and generate the so-called Pioneer Translation Products (PTPs), which are peptides generated from unspliced mRNA. We demonstrated in vitro and in vivo that the splicing inhibitor isoginkgetin and a derived water-soluble and less toxic molecule, IP2, act at the production stage of the PTPs. We showed that IP2 increases PTP-derived antigen presentation in cancer cellsin vitroand decreases tumor growthin vivoin an immune-dependent manner. Furthermore, IP2 treatment induces a long-lasting antitumor response. Finally, we observed that the epitope repertoire displayed on MHC-I molecules is altered upon treatment with IP2 with the modulation of pre-existing peptides and the emergence of novel antigens derived from both coding and allegedly non-coding sequences.

Significance

IP2 is a new efficient “first in class” immunomodulator of the MHC I presentation pathway. IP2 reduces the growth of sarcoma MCA205 and melanoma B16F10 tumors bearing the PTP-derived SL8 epitope and significantly extends mice survival. IP2 treatment reshape the cancer cell MHC-I immunopeptidome. These findings add to the understanding of the role of the splicing machinery in antigen production and presentation and identify the spliceosome as a druggable target to enhance cancer immunosurveillance.
Inhibition of miR-22-3p reduces kidney disease associated with systemic lupus erythematosus
Authors: Michell Danielle L. , Faust Ashley , Moore Jared L. , Appleton Brenna D. , Ormseth Michelle , Ramirez-Solano Marisol , Sheng Quanhu , Solus Joseph F. , Stein C. Michael , Vickers Kasey C. , Major Amy S.
Published: January 2019

Cellular microRNAs (miRNA) have proven to be critical regulators of inflammatory gene expression across many pathways within autoimmunity. Circulating miRNAs serve as a new class of disease biomarkers. Nevertheless, the functional roles of miRNAs, particularly extracellular miRNAs, in systemic lupus erythematosus (SLE) remain poorly understood. Therefore, we aimed to link changes in extracellular miRNAs to lymphocyte gene regulation and the pathophysiology of SLE. Here, we demonstrate that circulating miR-22-3p levels are associated with SLE, and miR-22-3p regulates T and B cell function and SLE-associated kidney disease. Based on high-throughput small RNA sequencing and real-time PCR, extracellular miR-22-3p levels were found to be significantly increased in whole plasma in human SLE subjects. To determine the functional impact of miR-22-3p in SLE, miR-22-3p loss-of-function studies were performed in a mouse model of SLE (B6.SLE1.2.3). We found thatin vivoadministration of locked-nucleic acid inhibitors of miR-22-3p (LNA-22) reduced lymphocyte accumulation in both the spleen and lymph nodes compared to LNA scramble (LNA-Scr) control-treated mice. Strikingly, LNA-22-3p treatments reduced kidney disease pathology and glomerular IgG deposition compared to LNA-Scr treatments in SLE mice. Moreover, miR-22-3p inhibition reduced the proportion of T effector memory IFN-γ producing CD4+T cells, suggesting that miR-22-3p regulates Th1 T cell differentiation. We also found that miR-22 inhibition in mice reduced STAT1 phosphorylation in the kidney which was correlated with loss of IFN-γ production by splenic CD4+T cells. In conclusion, our findings suggest that miR-22-3p is a critical regulator of SLE-associated CD4+T cell immunity and kidney disease. These results provide therapeutic potential for limiting splenic Th1 signaling and preventing the progression of lupus nephritis.

Key Findings

Extracellular miR-22-3p levels are significantly increased in plasma from human SLE subjects.

Inhibition of miR-22-3pin vivosignificantly reduced lymphocyte accumulation in both the spleen and lymph nodes in a mouse model of SLE, thus reducing splenomegaly and lymphadenopathy.

miR-22-3p inhibition significantly reduced IFN-γ expression and secretion from splenic T cell subsets.

Inhibition of miR-22-3pin vivoresulted in decreased IgG deposition in the kidney, decreased STAT1 phosphorylation, and decreased kidney disease in a mouse model of SLE.
Active cargo positioning in antiparallel transport networks
Authors: Richard Mathieu , Blanch-Mercader Carles , Ennomani Hajer , Cao Wenxiang , De La Cruz Enrique M. , Joanny Jean-François , Jülicher Frank , Blanchoin Laurent , Martin Pascal
Published: January 2019

Cytoskeletal filaments assemble into dense parallel, antiparallel or disordered networks, providing a complex environment for active cargo transport and positioning by molecular motors. The interplay between the network architecture and intrinsic motor properties clearly affects transport properties but remains poorly understood. Here, by using surface micro-patterns of actin polymerization, we investigate stochastic transport properties of colloidal beads in antiparallel networks of overlapping actin filaments. We found that 200-nm beads coated with myosin-Va motors displayed directed movements towards positions where the net polarity of the actin network vanished, accumulating there. The bead distribution was dictated by the spatial profiles of local bead velocity and diffusion coefficient, indicating that a diffusion-drift process was at work. Remarkably, beads coated with heavy mero-myosin-II motors showed a similar behavior. However, although velocity gradients were steeper with myosin II, the much larger bead diffusion observed with this motor resulted in less precise positioning. Our observations are well described by a three-state model, in which active beads locally sense the net polarity of the network by frequently detaching from and reattaching to the filaments. A stochastic sequence of processive runs and diffusive searches results in a biased random walk. The precision of bead positioning is set by the gradient of net actin polarity in the network and by the run length of the cargo in an attached state. Our results unveiled physical rules for cargo transport and positioning in networks of mixed polarity.

Significance statement

Cellular functions rely on small groups of molecular motors to transport their cargoes throughout the cell along polar filaments of the cytoskeleton. Cytoskeletal filaments self-assemble into dense networks comprising intersections and filaments of mixed polarity, challenging directed motor-based transport. Using micro-patterns of actin polymerization in-vitro, we investigated stochastic transport of colloidal beads in antiparallel networks of overlapping actin filaments. We found that beads coated with myosin motors sensed the net polarity of the actin network, resulting in active bead positioning to regions of neutral polarity with a precision depending on the motor type. A theoretical description of our experimental results provides the key physical rules for cargo transport and positioning in filament networks of mixed polarity.