bluuebunny/crossref_metadata_2025 huggingface dataset:
An Application of the Rational Expectations Hypothesis in the U.S. Beekeeping Industry
Authors: Willett Lois Schertz
Published: May 2019

A national beekeeping-industry model, assuming rational expectations, is presented.

Consistent and asymptotically efficient estimates are obtained by a modified two-step two-stage least squares method. Based on parameter estimates, elasticities, and likelihood functions, a previously estimated modified adaptive expectations model explains industry behavior better than the rational expectations model. Simulation analyses of the models suggest the direction of the impacts of an ineffective federal honey support program from 1982 through 1985 is similar but the magnitudes are varied. The rational expectations model indicates the decrease in beekeepers’ revenue in this period is larger than the decrease identified by the modified adaptive expectations model.
Fatal Farm Accidents in New York: Estimates of Their Costs
Authors: Kelsey Timothy W.
Published: May 2019

A telephone survey of all of the surviving families of people killed in farm accidents in New York between 1985 and 1987 (52 of 87 families interviewed, 60% response rate) found the average total annual present value of expected income foregone because of fatal farm accidents in New York is over $8.6 million (in 1987 dollars). Less than five years after the accidents, 67% of the families who operated the farms where the accidents occurred no longer operate them and 44% no longer live on the farms.
Cost Comparisons of Alternative Methods for Processing Recycled Waste Newspapers into Farm-Animal Bedding
Authors: Beierlein James G. , McSweeny William C. , Woodruff Barbara A.
Published: May 2019

The United States is facing a seemingly overwhelming problem of how to dispose of its solid waste. For disposal solutions to be viable, they must be environmentally sound and economically viable. Processing waste newspapers for farm-animal bedding offers a successful partial solution that meets both criteria. Centralized newspaper chopping is found to cost less than on-farm chopping. Both chopped and unchopped waste newspapers can be economically transported considerable distances. The use of waste newspapers for animal bedding is economically attractive at the farm level and can provide a partial solution to the solid-waste disposal problem.
A retrospective descriptive analysis of rabies post-exposure prophylaxis cases in Dalian from 2016 to 2017
Authors: Song Yi , Lu Xiaoguang , Jiang Xue , Zhao Weitong , Fan Zhiwei , Kang Xin , Wang Yu
Published: May 2019

Dalian, China, is a city free of rabies in recent 20 years, but the annual cost for rabies vaccination still brings an economic burden on society and individuals. We did a retrospective descriptive analysis to analyse the reason for this and try to find some ways to resolve it. A total of 10 028 post-exposure prophylaxis (PEP) cases were recorded from January 2016 to December 2017. According to the exposure grades, 32 cases were grade I; 7712 cases were grade II; 2284 cases were grade III. All the patients in the cases were injured by pet dogs without abnormal clinical signs, and 80% of them were home pet dogs. Fifty-two per cent of the pet dogs were vaccinated. All the dogs survived during the PEP vaccination period. The data showed that a considerable proportion of people who did not have exposure risk for rabies had received vaccination. The underlying reasons included social, medical and personal factors. So here we proposed to replace the current ‘five-course’ intramuscular injection with intradermal injection method in the cities free of rabies in China, this can not only achieve effective vaccination but also save resources and eliminate the fear of rabies from victims. Meanwhile we should strengthen communication on rabies knowledge and make a routine evaluation of rabies surveillance system to improve understanding of the risk for rabies from biting animals.
Stationary and ambulatory attention patterns are differentially associated with early temperamental risk for socioemotional problems: Preliminary evidence from a multimodal eye-tracking investigation
Authors: Fu Xiaoxue , Nelson Eric E. , Borge Marcela , Buss Kristin A. , Pérez-Edgar Koraly
Published: May 2019

Behavioral Inhibition (BI) is a temperament type that predicts social withdrawal in childhood and anxiety disorders later in life. However, not all BI children develop anxiety. Attention bias (AB) may enhance the vulnerability for anxiety in BI children, and interfere with their development of effective emotion regulation. In order to fully probe attention patterns, we used traditional measures of reaction time (RT), stationary eye-tracking, and recently emerging mobile eye-tracking measures of attention in a sample of 5- to 7-year-olds characterized as BI (N = 23) or non-BI (N = 58) using parent reports. There were no BI-related differences in RT or stationary eye-tracking indices of AB in a dot-probe task. However, findings in a subsample from whom eye-tracking data were collected during a live social interaction indicated that BI children (N = 12) directed fewer gaze shifts to the stranger than non-BI children (N = 25). Moreover, the frequency of gazes toward the stranger was positively associated with stationary AB only in BI, but not in non-BI, children. Hence, BI was characterized by a consistent pattern of attention across stationary and ambulatory measures. We demonstrate the utility of mobile eye-tracking as an effective tool to extend the assessment of attention and regulation to social interactive contexts.
Retrieving reusable software components by polymorphic type
Authors: Runciman Colin , Toyn Ian
Published: May 2019

Polymorphic types are labels classifying both (a) defined components in a library and (b) contexts of free variables in partially written programs. It is proposed to help programmers make better use of software libraries by providing a system that, given (b), identifies candidates from (a) with matching types. Assuming at first that matching means unifying (i.e. having a common instance), efficient ways of implementing such a retrieval system are discussed and its likely effectiveness based on a quantitative study of currently available libraries is indicated. The applicative instance relation between types, which captures some intuitions about generalization/specialization is then introduced, and its use as the basis of a more flexible system is discussed.
The Training and Generalisation of Conversation Skills with Moderately to Severely Handicapped Adolescents
Authors: Brigg John , Bain Alan , Houghton Stephen
Published: May 2019

This study utilised a Direct Instruction methodology to test the efficacy of small group social skills training on the acquisition and generalisation of conversational skills of three moderately to severely intellectually impaired adolescents. The results indicated a general increase in the conversational behaviour of the participants over the course of the intervention and that for two of the participants these changes generalised to a new setting with new conversational partners.
THE KUGA–SATAKE CONSTRUCTION UNDER DEGENERATION
Authors: Schreieder Stefan , Soldatenkov Andrey
Published: May 2019

We extend the Kuga–Satake construction to the case of limit mixed Hodge structures of K3 type. We use this to study the geometry and Hodge theory of degenerations of Kuga–Satake abelian varieties associated with polarized variations of K3 type Hodge structures over the punctured disc.
Begleitete minderjährige Geflüchtete
Authors: Piegenschke Katharina , Sihorsch Miriam , Christiansen Hanna
Published: May 2019

Zusammenfassung. Aufgrund erhöhter psychopathologischer Vulnerabilität bei minderjährigen Geflüchteten (MG), sind wirksame psychotherapeutische Interventionen versorgungsrelevant. Die Mehrzahl MG flieht im Familienverbund. Die Familie wirkt dabei einerseits als stabilisierende Ressource, anderseits als Stressor, so dass der Einbezug der Eltern in die Therapie von Bedeutung ist. Dieses Reviews gibt einen Überblick über den aktuellen Forschungsstand zur Wirksamkeit psychotherapeutischer Maßnahmen mit Familieneinbezug bei begleiteten minderjährigen Geflüchteten (BMG). Insgesamt konnten fünf Studien identifiziert werden. Für die Kinder wurden in vier der fünf, für die Mütter in zwei der fünf Studien signifikante Effekte berichtet. Insgesamt ist die Befundlage gering und die Qualität der Primärstudien oft unzureichend. Replikationen der Ergebnisse unter Berücksichtigung der methodischen Qualität sowie die Implementierung weiterer Maßnahmen sind notwendig.
Testing Hypotheses About Binding in Context Memory With a	Hierarchical Multinomial Modeling Approach
Authors: Arnold Nina R. , Heck Daniel W. , Bröder Arndt , Meiser Thorsten , Boywitt C. Dennis
Published: May 2019

Abstract. In experiments on multidimensional source memory, a stochastic dependency of source memory for different facets of an episode has been repeatedly demonstrated. This may suggest an integrated representation leading to mutual cuing in context retrieval. However, experiments involving a manipulated reinstatement of one source feature have often failed to affect retrieval of the other feature, suggesting unbound features or rather item-feature binding. The stochastic dependency found in former studies might be a spurious correlation due to aggregation across participants varying in memory strength. We test this artifact explanation by applying a hierarchical multinomial model. Observing stochastic dependency when accounting for interindividual differences would rule out the artifact explanation. A second goal is to elucidate the nature of feature binding: Contrasting encoding conditions with integrated feature judgments versus separate feature judgments are expected to induce different levels of stochastic dependency despite comparable overall source memory if integrated representations include feature-feature binding. The experiment replicated the finding of stochastic dependency and, thus, ruled out an artifact interpretation. However, we did not find different levels of stochastic dependency between conditions. Therefore, the current findings do not reveal decisive evidence to distinguish between the feature-feature binding and the item-context binding account.
High‐Resolution Mapping of Yield Curve Shape and Evolution for High‐Porosity Sandstone
Authors: Bedford John D. , Faulkner Daniel R. , Wheeler John , Leclère Henri
Published: May 2019

Understanding the onset and nature of inelastic deformation in porous rock is important for a range of geological and geotechnical problems. In particular for sandstones and siliciclastic sediments, which often act as hydrocarbon reservoirs, inelastic strain can significantly alter the permeability affecting productivity or storativity. The onset of inelastic strain is defined by a yield curve plotted in effective mean stress (P) versus differential stress (Q) space. Yield curves for porous sandstone typically have a broadly elliptical shape, with the low‐pressure side associated with localized brittle faulting (dilation) and the high‐pressure side with distributed ductile deformation (compaction). However, recent works have shown that, for different porous rocks, the curve shape can evolve significantly with the accumulation of inelastic strain. Here yield curve shape and evolution of two high‐porosity sandstones (36–38%) is mapped along different loading paths using a high‐resolution technique on single samples. The data reveal yield curves with a relatively shallow geometry and with a compactive side that is partly comprised of a near‐vertical limb. Yield curve evolution is found to be strongly dependent on the nature of inelastic strain with samples compacted under a deviatoric load (i.e., with a component of shear strain) having peak stress values that are approximately 3 times greater than similar porosity samples compacted under a hydrostatic load (i.e., purely volumetric strain). These results have important implications for predicting how the strength of porous rock evolves along different stress paths, which differ in reservoirs during burial, fluid extraction, or injection.
Modeled MABL Responses to the Winter Kuroshio SST Front in the East China Sea and Yellow Sea
Authors: Bai HaoKun , Hu HaiBo , Yang Xiu‐Qun , Ren XueJuan , Xu HaiMing , Liu GuoQiang
Published: May 2019

Based on the Weather Research Forecasting (WRF) model, we designed a long‐term sea surface temperature (SST)‐forcing simulation to simulate the influences of SST front on the marine atmospheric boundary layer (MABL) over the East China Sea and the Yellow Sea during wintertime. The results revealed that SST front have significant relationship with MABL adjustment. The atmospheric modulations and the comparisons of the vector wind and the scalar wind indicate that the MABL responses to the SST front are quite different under different wind directions. When the prevailing wind blows parallel to the SST front (NE wind directions), the sea level pressure adjustment mechanism dominates the atmospheric adjustment. The variances of scalar wind and vector wind are similar. However, when prevailing wind crossing SST front from cold to warm (NW wind directions), both the sea level pressure adjustment mechanism and vertical mixing mechanism play an important role. The maximum variations of the scalar wind are just over the core of SST front, whereas maximum vector wind variations are over warm flank. When wind blowing from warm to cold (SE wind directions), the vertical mixing mechanism contributes more to the MABL responses. The maximum variations of the scalar wind are beyond the top of MABL, which occur over the core SST front. The further diagnosis analysis showed that the meridional transient eddies and mean flow interaction contribute to the scalar wind variations under cross‐front conditions.
Testing Model Representations of Snowpack Liquid Water Percolation Across Multiple Climates
Authors: Pflug J. M. , Liston G. E. , Nijssen B. , Lundquist J. D.
Published: May 2019

Snowpack liquid water percolation is a sensitive model process that is crucial for snowpack runoff forecasts yet varies in sensitivity between climates and snow seasons. Therefore, models of varied complexity developed for different climates and purposes use different percolation representations. We investigated how liquid fluxes in a multilayer snow model vary as represented by discrete representations of gravity drainage and snow density thresholds. We evaluated performance and sensitivity to nonphysical parameters using point measurements of snow water equivalent (SWE) at a maritime site in Washington, USA, and measurements of both SWE and runoff in the French and Swiss Alps. At all three locations, the gravity drainage simulations reduced parameter sensitivity and increased model performance. Average Nash‐Sutcliffe efficiency improved from 0.06 to 0.61 between density threshold and gravity drainage simulations with default parameters. The disparity in model performance was particularly evident at the maritime site (Washington, USA), where the gravity drainage peak SWE was biased by 6% (0.10 m) but density threshold peak SWE was biased by 85% (1.51 m). Simulated runoff and SWE also decreased in performance and increased in parameter sensitivity when including a widely used two‐layer percolation routine. This demonstrates the importance of testing and evaluating models across a wide range of climates, with close attention paid to warmer regions, where percolation has high parameter sensitivity. This is particularly important for global snow modeling and climate change scenarios where multiple regions and snow seasons must be adequately represented with a single model implementation.
JGR: Planets and a Community of Planetary Science
Authors: Hauck II Steven
Published: May 2019

The outgoing Editor-in-Chief of JGR: Planets reflects on the journal’s role serving the planetary science community and expresses appreciation for all those who contribute to its success.
Deep Water Cycling and Sea Level Change Since the Breakup of Pangea
Authors: Karlsen Krister S. , Conrad Clinton P. , Magni Valentina
Published: May 2019

First‐order variations in sea level exhibit amplitudes of ∼200 m over periods that coincide with those of supercontinental cycles (∼300–500 Myr). Proposed mechanisms for this sea level change include processes that change the container volume of the ocean basins and the relative elevation of continents. Here we investigate how unbalanced rates of water exchange between Earth's surface and mantle interior, resulting from fluctuations in tectonic rates, can cause sea level changes. Previous modeling studies of subduction water fluxes suggest that the amount of water that reaches sub‐arc depths is well correlated with the velocity and age of the subducting plate. We use these models to calibrate a parameterization of the deep subduction water flux, which we together with a parameterization of mid‐ocean ridge outgassing, then apply to reconstructions of Earth's tectonic history. This allows us to estimate the global water fluxes between the oceans and mantle for the past 230 Myr and compute the associated sea level change. Our model suggests that a sea level drop of up to 130 m is possible over this period and that it was partly caused by the ∼150Ma rift pulse that opened the Atlantic and forced rapid subduction of old oceanic lithosphere. This indicates that deep water cycling may be one of the more important sea level changing mechanisms on supercontinental time scales and provides a more complete picture of the dynamic interplay between tectonics and sea level change.
Detectability of Remanent Magnetism in the Crust of Venus
Authors: O'Rourke J. G. , Buz J. , Fu R. R. , Lillis R. J.
Published: May 2019

Observations of planetary magnetic fields provide fundamental insights into the origin and evolution of terrestrial planets. However, whether Venus ever hosted a dynamo is unknown. Here we show that crustal remanent magnetism is a potentially observable consequence of an ancient Venusian dynamo, in contrast to previous studies that dismissed this possibility. Past spacecraft measurements only exclude crustal magnetization near the Venera 4 landing site and northward of 50° South latitude for >150‐km coherence scales and strong magnetization intensities. Magnetite grains with sizes commonly observed in volcanic rocks can retain thermoremanent magnetism at Venusian conditions for >1 billion years. Depths to the Curie temperature of magnetite are ~5–40 km and typically less than predicted crustal thicknesses at our analyzed localities. Aerial platforms could detect expected magnetizations at horizontal scales similar to the ~50‐km operating altitude. Any detection would validate models of planetary accretion, geologic processes, and climate history.
PMC Turbo: Studying Gravity Wave and Instability Dynamics in the Summer Mesosphere Using Polar Mesospheric Cloud Imaging and Profiling From a Stratospheric Balloon
Authors: Fritts David C. , Miller Amber D. , Kjellstrand C. Bjorn , Geach Christopher , Williams Bifford P. , Kaifler Bernd , Kaifler Natalie , Jones Glenn , Rapp Markus , Limon Michele , Reimuller Jason , Wang Ling , Hanany Shaul , Gisinger Sonja , Zhao Yucheng , Stober Gunter , Randall Cora E.
Published: May 2019

The Polar Mesospheric Cloud Turbulence (PMC Turbo) experiment was designed to observe and quantify the dynamics of small‐scale gravity waves (GWs) and instabilities leading to turbulence in the upper mesosphere during polar summer using instruments aboard a stratospheric balloon. The PMC Turbo scientific payload comprised seven high‐resolution cameras and a Rayleigh lidar. Overlapping wide and narrow camera field of views from the balloon altitude of ~38 km enabled resolution of features extending from ~20 m to ~100 km at the PMC layer altitude of ~82 km. The Rayleigh lidar provided profiles of temperature below the PMC altitudes and of the PMCs throughout the flight. PMCs were imaged during an ~5.9‐day flight from Esrange, Sweden, to Northern Canada in July 2018. These data reveal sensitivity of the PMCs and the dynamics driving their structure and variability to tropospheric weather and larger‐scale GWs and tides at the PMC altitudes. Initial results reveal strong modulation of PMC presence and brightness by larger‐scale waves, significant variability in the occurrence of GWs and instability dynamics on time scales of hours, and a diversity of small‐scale dynamics leading to instabilities and turbulence at smaller scales. At multiple times, the overall field of view was dominated by extensive and nearly continuous GWs and instabilities at horizontal scales from ~2 to 100 km, suggesting sustained turbulence generation and persistence. At other times, GWs were less pronounced and instabilities were localized and/or weaker, but not absent. An overview of the PMC Turbo experiment motivations, scientific goals, and initial results is presented here.
August‐September Temperature Variability on the Tibetan Plateau: Past, Present, and Future
Authors: Duan Jianping , Ma Zhuguo , Li Lun , Zheng Ziyan
Published: May 2019

To assess the recent warming on the Tibetan Plateau (TP), some tree‐ring‐based temperature reconstructions have been performed. However, most of the previous studies focused on the local or regional scale. In this study, we analyzed the recent variability of August‐September temperature using observations from 79 TP meteorological stations, and the observed records were extended back to 1,572 based on a tree‐ring maximum density network comprising 17 sites. Moreover, the future August‐September temperature scenarios on the TP are also presented using the ensemble mean of five regional climate models. The tree‐ring maximum late‐wood density network shows good capacity to reconstruct the August‐September temperature variability at the spatial scale of the whole TP (i.e., 79‐station average; r1951–2014 = 0.80, P < 0.01). The reconstruction suggests that the instrumental epoch is the warmest interval of August‐September over the past four and a half centuries on the TP, and the decadal‐scale August‐September warming since the 1960s is unprecedented. The ensemble simulation of five regional climate models indicates that persistent August‐September warming will occur on the TP in the future. The magnitude of August‐September warming is approximately 1.56 ± 0.30°C and 3.02 ± 0.29°C over the period 2006–2049 under the Representative Concentration Pathways (RCPs) 4.5 and P8.5 scenarios, respectively. These results imply a further ecological and environmental change on the TP linked to the persistent warming in the future.
A Thermal Inertia Map of Titan
Authors: MacKenzie Shannon M. , Lora Juan M. , Lorenz Ralph D.
Published: May 2019

Like Earth, the atmosphere of Titan, Saturn's largest moon, is affected by the ability of the surface to store and release heat. Modeling efforts have shown that global temperature distributions and wind profiles differ between simulations describing Titan's surface with a uniform thermal inertia. Cassini‐Huygens demonstrated, however, that a variety of morphologies and compositions make up the Titanian landscape. Using data from Cassini RADAR and the Visible and Infrared Mapping Spectrometer, we classified the surface into five terrain types: dune, lake, hummocky, plains, and labyrinth. We estimated the thermal and physical properties (conductivity, specific heat, and density) for each type, creating a 1° × 1° global map of thermal inertia values. For the lakes, as the depth of convection is not yet known, we considered both still and convective bodies. Four simulations of the Titan Atmospheric Model were run with different surface thermal properties: a low homogeneous thermal inertia, a moderate homogeneous, the heterogeneous map with still lakes, and the heterogeneous map with convective lakes. In dry regimes (i.e., without the hydrological cycle), the differences between the four cases were generally minimal, suggesting that general circulation models can use a single (moderate) value for surface thermal inertia value for large‐scale investigations that do not consider diurnal variations. Given the importance of hydrological processes and regional spatial diversity on Titan, future work should consider the effects of nonuniform thermal inertia on Titan's climate on local and regional scales.
Fine Vertical Resolution Radiative‐Convective Equilibrium Experiments: Roles of Turbulent Mixing on the High‐Cloud Response to Sea Surface Temperatures
Authors: Ohno Tomoki , Satoh Masaki , Noda Akira
Published: May 2019

In this study, the vertical resolution dependency of the high‐cloud fraction response on the increase in sea surface temperature was investigated via radiative‐convective equilibrium simulations. We performed radiative‐convective equilibrium simulations for configurations with a wide range of vertical resolutions using a global nonhydrostatic model including explicit cloud microphysics. It was found that the high‐cloud cover almost monotonically decreased as the vertical resolution increased. We also found that the high‐cloud cover increased (decreased) as the sea surface temperature increased for higher (lower) vertical resolutions. Budget analyses of ice water condensate in transition states to equilibria were performed using the binned vertical profile method and revealed that the tendencies due to the turbulent mixing near convective cores were strongly dependent on the vertical resolution. Analyses of turbulent diffusivity profiles showed that the diffusivity tended to decrease as the vertical resolution increased. The vertical resolution dependency of turbulent mixing was related to frequently occurring weak stratification near the convective cores. We verified these findings via sensitivity experiments and determined that the contribution of the vertical resolution dependency of other processes was secondary. As substantial variability in vertical diffusivity has been reported in both models and observations, these results suggest that a more thorough understanding of turbulent mixing is needed to comprehend high‐cloud changes in warming climates better.
MALAT1 regulates miR-34a expression in melanoma cells
Authors: Li Fei , Li Xinji , Qiao Li , Liu Wen , Xu Chengshan , Wang Xiaogang
Published: May 2019

Melanoma is one of the most common skin malignancies. Both microRNAs and long non-coding RNAs (lncRNAs) have critical roles in the progression of cancers, including melanoma. However, the underlying molecular mechanism has not been fully characterized. We demonstrated that miR-34a is negatively correlated with MALAT1 in melanoma cells and tumor specimens. Interestingly, MALAT1, which contains functional sequence-specific miR-34a-binding sites, regulates miR-34a stability in melanoma cells and in vivo. Importantly, MALAT1 was significantly enriched in the Ago2 complex, but not when the MALAT1-binding site of miR-34a was mutated. Furthermore, MALAT1 could be shown to regulate c-Myc and Met expression by functioning as a miR-34a sponge. Our results reveal an unexpected mode of action for MALAT1 as an important regulator of miR-34a.
Surmounting Cytarabine-resistance in acute myeloblastic leukemia cells and specimens with a synergistic combination of hydroxyurea and azidothymidine
Authors: Levin May , Stark Michal , Berman Bluma , Assaraf Yehuda G.
Published: May 2019

Acute myeloid leukemia (AML) patients display dismal prognosis due to high prevalence of refractory and relapsed disease resulting from chemoresistance. Treatment protocols, primarily based on the anchor drug Cytarabine, remained chiefly unchanged in the past 50 years with no standardized salvage regimens. Herein we aimed at exploring potential pre-clinical treatment strategies to surmount Cytarabine resistance in human AML cells. We established Cytarabine-resistant sublines derived from human leukemia K562 and Kasumi cells, and characterized the expression of Cytarabine-related genes using real-time PCR and Western blot analyses to uncover the mechanisms underlying their Cytarabine resistance. This was followed by growth inhibition assays and isobologram analyses testing the sublines’ sensitivity to the clinically approved drugs hydroxyurea (HU) and azidothymidine (AZT), compared to their parental cells. All Cytarabine-resistant sublines lost deoxycytidine kinase (dCK) expression, rendering them refractory to Cytarabine. Loss of dCK function involved dCK gene deletions and/or a novel frameshift mutation leading to dCK transcript degradation via nonsense-mediated decay. Cytarabine-resistant sublines displayed hypersensitivity to HU and AZT compared to parental cells; HU and AZT combinations exhibited a marked synergistic growth inhibition effect on leukemic cells, which was intensified upon acquisition of Cytarabine-resistance. In contrast, HU and AZT combination showed an antagonistic effect in non-malignant cells. Finally, HU and AZT synergism was demonstrated on peripheral blood specimens from AML patients. These findings identify a promising HU and AZT combination for the possible future treatment of relapsed and refractory AML, while sparing normal tissues from untoward toxicity.
Skin immunisation activates an innate lymphoid cell-monocyte axis regulating CD8+ effector recruitment to mucosal tissues
Authors: Zaric Marija , Becker Pablo D. , Hervouet Catherine , Kalcheva Petya , Doszpoly Andor , Blattman Negin , A. O’ Neill Lauren , Yus Barbara Ibarzo , Cocita Clement , Kwon Sung-Yun , Baker Andrew H. , Lord Graham M. , Klavinskis Linda S.
Published: May 2019

CD8+T cells provide a critical defence from pathogens at mucosal epithelia including the female reproductive tract (FRT). Mucosal immunisation is considered essential to initiate this response, however this is difficult to reconcile with evidence that antigen delivered to skin can recruit protective CD8+T cells to mucosal tissues. Here we dissect the underlying mechanism. We show that adenovirus serotype 5 (Ad5) bio-distributes at very low level to non-lymphoid tissues after skin immunisation. This drives the expansion and activation of CD3−NK1.1+group 1 innate lymphoid cells (ILC1) within the FRT, essential for recruitment of CD8+T-cell effectors. Interferon gamma produced by activated ILC1 is critical to licence CD11b+Ly6C+monocyte production of CXCL9, a chemokine required to recruit skin primed CXCR3+CD8+T-cells to the FRT. Our findings reveal a novel role for ILC1 to recruit effector CD8+T-cells to prevent virus spread and establish immune surveillance at barrier tissues.
ALPK1 hotspot mutation as a driver of human spiradenoma and spiradenocarcinoma
Authors: Rashid Mamunur , van der Horst Michiel , Mentzel Thomas , Butera Francesca , Ferreira Ingrid , Pance Alena , Rütten Arno , Luzar Bostjan , Marusic Zlatko , de Saint Aubain Nicolas , Ko Jennifer S. , Billings Steven D. , Chen Sofia , Abi Daoud Marie , Hewinson James , Louzada Sandra , Harms Paul W. , Cerretelli Guia , Robles-Espinoza Carla Daniela , Patel Rajiv M. , van der Weyden Louise , Bakal Chris , Hornick Jason L. , Arends Mark J. , Brenn Thomas , Adams David J.
Published: May 2019

Spiradenoma and cylindroma are distinctive skin adnexal tumors with sweat gland differentiation and potential for malignant transformation and aggressive behaviour. We present the genomic analysis of 75 samples from 57 representative patients including 15 cylindromas, 17 spiradenomas, 2 cylindroma–spiradenoma hybrid tumors, and 24 low- and high-grade spiradenocarcinoma cases, together with morphologically benign precursor regions of these cancers. We reveal somatic or germline alterations of the CYLD gene in 15/15 cylindromas and 5/17 spiradenomas, yet only 2/24 spiradenocarcinomas. Notably, we find a recurrent missense mutation in the kinase domain of the ALPK1 gene in spiradenomas and spiradenocarcinomas, which is mutually exclusive from mutation of CYLD and can activate the NF-κB pathway in reporter assays. In addition, we show that high-grade spiradenocarcinomas carry loss-of-function TP53 mutations, while cylindromas may have disruptive mutations in DNMT3A. Thus, we reveal the genomic landscape of adnexal tumors and therapeutic targets.
Development of hRad51–Cas9 nickase fusions that mediate HDR without double-stranded breaks
Authors: Rees Holly A. , Yeh Wei-Hsi , Liu David R.
Published: May 2019

In mammalian cells, double-stranded DNA breaks (DSBs) are preferentially repaired through end-joining processes that generally lead to mixtures of insertions and deletions (indels) or other rearrangements at the cleavage site. In the presence of homologous DNA, homology-directed repair (HDR) can generate specific mutations, albeit typically with modest efficiency and a low ratio of HDR products:indels. Here, we develop hRad51 mutants fused to Cas9(D10A) nickase (RDN) that mediate HDR while minimizing indels. We use RDN to install disease-associated point mutations in HEK293T cells with comparable or better efficiency than Cas9 nuclease and a 2.7-to-53-fold higher ratio of desired HDR product:undesired byproducts. Across five different human cell types, RDN variants generally result in higher HDR:indel ratios and lower off-target activity than Cas9 nuclease, although HDR efficiencies remain strongly site- and cell type-dependent. RDN variants provide precision editing options in cell types amenable to HDR, especially when byproducts of DSBs must be minimized.
Real space manifestations of coherent screening in atomic scale Kondo lattices
Authors: Moro-Lagares María , Korytár Richard , Piantek Marten , Robles Roberto , Lorente Nicolás , Pascual Jose I. , Ibarra M. Ricardo , Serrate David
Published: May 2019

The interaction among magnetic moments screened by conduction electrons drives quantum phase transitions between magnetically ordered and heavy-fermion ground states. Here, starting from isolated magnetic impurities in the Kondo regime, we investigate the formation of the finite size analogue of a heavy Fermi liquid. We build regularly-spaced chains of Co adatoms on a metallic surface by atomic manipulation. Scanning tunneling spectroscopy is used to obtain maps of the Kondo resonance intensity with sub-atomic resolution. For sufficiently small interatomic separation, the spatial distribution of Kondo screening does not coincide with the position of the adatoms. It also develops enhancements at both edges of the chains. Since we can rule out any other interaction between Kondo impurities, this is explained in terms of the indirect hybridization of the Kondo orbitals mediated by a coherent electron gas, the mechanism that causes the emergence of heavy quasiparticles in the thermodynamic limit.
Airway response to respiratory syncytial virus has incidental antibacterial effects
Authors: Sande Charles J. , Njunge James M. , Mwongeli Ngoi Joyce , Mutunga Martin N. , Chege Timothy , Gicheru Elijah T. , Gardiner Elizabeth M. , Gwela Agnes , Green Christopher A. , Drysdale Simon B. , Berkley James A. , Nokes D. James , Pollard Andrew J.
Published: May 2019

RSV infection is typically associated with secondary bacterial infection. We hypothesise that the local airway immune response to RSV has incidental antibacterial effects. Using coordinated proteomics and metagenomics analysis we simultaneously analysed the microbiota and proteomes of the upper airway and determined direct antibacterial activity in airway secretions of RSV-infected children. Here, we report that the airway abundance ofStreptococcuswas higher in samples collected at the time of RSV infection compared with samples collected one month later. RSV infection is associated with neutrophil influx into the airway and degranulation and is marked by overexpression of proteins with known antibacterial activity including BPI, EPX, MPO and AZU1. Airway secretions of children infected with RSV, have significantly greater antibacterial activity compared to RSV-negative controls. This RSV-associated, neutrophil-mediated antibacterial response in the airway appears to act as a regulatory mechanism that modulates bacterial growth in the airways of RSV-infected children.
Fast and interpretable classification of small X-ray diffraction datasets using data augmentation and deep neural networks
Authors: Oviedo Felipe , Ren Zekun , Sun Shijing , Settens Charles , Liu Zhe , Hartono Noor Titan Putri , Ramasamy Savitha , DeCost Brian L. , Tian Siyu I. P. , Romano Giuseppe , Gilad Kusne Aaron , Buonassisi Tonio
Published: May 2019

X-ray diffraction (XRD) data acquisition and analysis is among the most time-consuming steps in the development cycle of novel thin-film materials. We propose a machine learning-enabled approach to predict crystallographic dimensionality and space group from a limited number of thin-film XRD patterns. We overcome the scarce data problem intrinsic to novel materials development by coupling a supervised machine learning approach with a model-agnostic, physics-informed data augmentation strategy using simulated data from the Inorganic Crystal Structure Database (ICSD) and experimental data. As a test case, 115 thin-film metal-halides spanning three dimensionalities and seven space groups are synthesized and classified. After testing various algorithms, we develop and implement an all convolutional neural network, with cross-validated accuracies for dimensionality and space group classification of 93 and 89%, respectively. We propose average class activation maps, computed from a global average pooling layer, to allow high model interpretability by human experimentalists, elucidating the root causes of misclassification. Finally, we systematically evaluate the maximum XRD pattern step size (data acquisition rate) before loss of predictive accuracy occurs, and determine it to be 0.16° 2θ, which enables an XRD pattern to be obtained and classified in 5.5 min or less.
Suppression of R5-type of HIV-1 in CD4+ NKT cells by Vδ1+ T cells activated by flavonoid glycosides, hesperidin and linarin
Authors: Yonekawa Michiyuki , Shimizu Masumi , Kaneko Atsushi , Matsumura Jiro , Takahashi Hidemi
Published: May 2019

We established transfectants expressing T cell receptors (TCRs) either for Vγ1 and Vδ1 (1C116) or for Vγ2 and Vδ2 (2C21) using the TCR-deficient Jurkat T cell line J.RT3-T3.5. The amount of IL-2 secreted from these γδ T cell clones accurately indicated TCR-dependent stimulation. Clone 2C21 was specifically stimulated by previously reported ligands for Vγ2Vδ2 (Vδ2)-TCR such as isopentenyl pyrophospate (IPP), ethylamine, or risedronate. In contrast, clone 1C116 was strongly stimulated through the Vγ1Vδ1 (Vδ1)-TCR by flavonoid glycosides such as hesperidin and linarin, having both rutinose at the A ring and methoxy (-OCH3) substitution at the B ring. Additionally, hesperidin and linarin showed stimulatory activity for peripheral blood mononuclear cell (PBMC)-derived T cells expressing Vδ1-TCR; these activated Vδ1+T cells also secreted IL-5, IL-13, MIP-1α, MIP-1β and RANTES. Such PBMC-derived Vδ1+T cells stimulated by hesperidin and linarin suppressed R5-HIV-1-NL(AD8) viral replication in CD4+NKT cells in a dose-dependent manner. To the best of our knowledge, this is the first demonstration that flavonoid glycosides activate functional Vδ1+T cells.
Accounting for soil moisture improves prediction of flowering time in chickpea and wheat
Authors: Chauhan Yashvir S. , Ryan Merrill , Chandra Subhash , Sadras Victor O.
Published: May 2019

Matching crop phenology to environment is essential to improve yield and reduce risk of losses due to extreme temperatures, hence the importance of accurate prediction of flowering time. Empirical evidence suggests that soil water can influence flowering time in chickpea and wheat, but simulation models rarely account for this effect. Adjusting daily thermal time accumulation with fractional available soil water in the 0–60 cm soil layer improved the prediction of flowering time for both chickpea and wheat in comparison to the model simulating flowering time with only temperature and photoperiod. The number of post-flowering frost events accounted for 24% of the variation in observed chickpea yield using a temperature-photoperiod model, and 66% of the variation in yield with a model accounting for top-soil water content. Integrating the effect of soil water content in crop simulation models could improve prediction of flowering time and abiotic stress risk assessment.
Several biological benefits of the low color temperature light-emitting diodes based normal indoor lighting source
Authors: Lin Jiaqi , Ding Xingwei , Hong Can , Pang Yulian , Chen Liming , Liu Quanwen , Zhang Xu , Xin Hongbo , Wang Xiaolei
Published: May 2019

Currently, light pollution has become a nonnegligible issue in our daily life. Artificial light sources with high color temperature were deem to be the major pollution source, which could induce several adverse effects on human’s health. In our previous research, we have firstly developed an artificial indoor light with low color temperature (1900 K). However, the biological effects of this artificial light on human’s health are unclear. Here, four artificial lights (1900 K, 3000 K, 4000 K and 6600 K) were used to evaluate some biological changes in both human (in total 152 person-times) and murine models. Compared with other three high color temperature artificial lights, our lights (1900 K) presented a positive effect on promoting the secreting of melatonin and glutamate, protecting human’s eyes, accelerating would healing and hair regeneration. These systematical studies indicated that the proposed low color temperature (1900 K) light could provide several significant benefits in human’s daily life.
Th1, Th17, and Treg Responses are Differently Modulated by TNF-α Inhibitors and Methotrexate in Psoriasis Patients
Authors: Furiati Sandro C. , Catarino Jonatas S. , Silva Marcos V. , Silva Rafaela F. , Estevam Rayane B. , Teodoro Reginaldo B. , Pereira Sanivia L. , Ataide Meire , Rodrigues Virmondes , Rodrigues Denise B. R.
Published: May 2019

Psoriasis is a chronic, recurrent, immune-mediated, hyperproliferative inflammatory skin disease. The role of the adaptive immune system, particularly of Th1 and Th17 lymphocytes, has been regarded as prominent in the immunopathogenesis of psoriasis, as well as decreased Tregs function. Immunobiological drugs were administered in therapeutic pulses and a few studies evaluate their effects on the immune repertoire. The aim of this study was to evaluate the adaptive immune profile of patients with severe psoriasis under immunobiological treatment in two time points. Thirty-two psoriasis patients and 10 control patients were evaluated. In the group of psoriasis patients, 10 patients were on anti-TNF and 14 patients on methotrexate treatment, while 8 individuals were not treated. IL-17, IFN-γ, TNF-α, IL-6, IL-2, and IL-10 were analyzed. CD4 T cell intracellular cytokines were analyzed. It was observed that stimulation could significantly increase the production of IL-17, IFN-γ, TNF-α, and IL-10 only before anti-TNF pulse therapy. The activation of Th1 and Treg cells after stimulation was significantly higher before anti-TNF pulse. Patients on methotrexate or anti-TNF therapy produced significantly lower levels of TNF-α, IL-10, and IL-6. Furthermore, these patients showed a significant decrease in the activated CD4+ T cells. The treatment with immunomodulator or methotrexate modulates the activation of CD4+ T cells, and anti-TNF treatment appears to have a modulating effect on the activation and production of Th1, Th17, and Treg cells.
Plk1 Mediates Paxillin Phosphorylation (Ser-272), Centrosome Maturation, and Airway Smooth Muscle Layer Thickening in Allergic Asthma
Authors: Rezey Alyssa C. , Gerlach Brennan D. , Wang Ruping , Liao Guoning , Tang Dale D.
Published: May 2019

Allergic asthma is characterized by airway smooth muscle layer thickening, which is largely attributed to cell division that requires the formation of centrosomes. Centrosomes play a pivotal role in regulating bipolar spindle formation and cell division. Before mitosis, centrosomes undergo maturation characterized by expansion of pericentriolar material proteins, which facilitates spindle formation and mitotic efficiency of many cell types. Although polo-like kinase 1 (Plk1) has been implicated in centrosome maturation, the mechanisms by which Plk1 regulates the cellular process are incompletely elucidated. Here, we identified paxillin as a new Plk1-interacting protein in human airway smooth muscle cells. We unexpectedly found that phosphorylated paxillin (Ser-272) was localized in centrosomes of human smooth muscle cells, which regulated centrosome maturation and spindle assembly. Plk1 knockdown inhibited paxillin Ser-272 phosphorylation, centrosome maturation, and cell division. Furthermore, exposure to allergens enhanced airway smooth muscle layer and paxillin phosphorylation at this residue in mice, which was reduced by smooth muscle conditional knockout of Plk1. These findings suggest that Plk1 regulates centrosome maturation and cell division in part by modulating paxillin phosphorylation on Ser-272. Furthermore, Plk1 contributes to the pathogenesis of allergen-induced thickening of the airway smooth muscle layer by affecting paxillin phosphorylation at this position.
Fish diversity of the largest deltaic formation in the Americas - a description of the fish fauna of the Parnaíba Delta using DNA Barcoding
Authors: Guimarães-Costa Aurycéia J. , Machado Fabíola S. , Oliveira Rory R. S. , Silva-Costa Vinícius , Andrade Marcelo C. , Giarrizzo Tommaso , Saint-Paul Ulrich , Sampaio Iracilda , Schneider Horacio
Published: May 2019

Deltas are dynamic and productive systems of enormous ecological significance, encompassing unique and biologically diverse wetland habitats. Here, we present the first data on the molecular diversity of the fish fauna of the Parnaíba Delta, the largest deltaic formation of the Americas. Partial sequences (626 bp) of the mitochondrial COI gene (Cytochrome c oxidase subunit I) were used to barcode 402 individuals, representing 128 species, belonging to 98 genera, 57 families, 17 orders and two classes. The most abundant orders were the Perciformes, Siluriformes, Gobiiformes, and Pleuronectiformes. The Neighbor-Joining (NJ), Bayesian Inference (BI), and BIN analyses produced 103 molecular clusters, while the Automatic Barcode Gap Discovery (ABGD) and Maximum Likelihood (ML) approaches revealed 102 clusters. The mean conspecific, congeneric and confamilial genetic distances were 0.33%, 14.37%, and 18.60%, respectively. Intraspecific divergence ranged from 0.0% to 1.4%, and all species presented barcode gaps, with the exception of two clusters of Cathorops spixii (OTU 96 and OTU 103), which were separated by a low interspecific distance (1.2%), which overlaps the maximum intraspecific genetic distance (1.4%). The barcode data provide new insights into the fish diversity of the Parnaíba Delta, which will be important for the development of further research on this fauna.
Imaging of dehydration in particulate matter using Raman line-focus microscopy
Authors: Okeyo Peter Ouma , Ilchenko Oleksii , Slipets Roman , Larsen Peter Emil , Boisen Anja , Rades Thomas , Rantanen Jukka
Published: May 2019

Crystalline solids can incorporate water molecules into their crystal lattice causing a dramatic impact on their properties. This explains the increasing interest in understanding the dehydration pathways of these solids. However, the classical thermal analytical techniques cannot spatially resolve the dehydration pathway of organic hydrates at the single particle level. We have developed a new method for imaging the dehydration of organic hydrates using Raman line-focus microscopy during heating of a particle. Based on this approach, we propose a new metastable intermediate of theophylline monohydrate during the three-step dehydration process of this system and further, we visualize the complex nature of the three-step dehydration pathway of nitrofurantoin monohydrate to its stable anhydrous form. A Raman line-focus mapping option was applied for fast simultaneous mapping of differently sized and shaped particles of nitrofurantoin monohydrate, revealing the appearance of multiple solid-state forms and the non-uniformity of this particle system during the complex dehydration process. This method provides an in-depth understanding of phase transformations and can be used to explain practical industrial challenges related to variations in the quality of particulate materials.