bluuebunny/crossref_metadata_2025 huggingface dataset:
Multichannel unidirectional perfect absorbers on sandwich structures with truncated symmetric photonic crystals
Authors: Lu Guang , Cui Liyong , Liu Bin , Li Jin , Sun Feng , Zhang Shan , Liu Fen , Li Yanhui , Yang Tianlin , Du Guiqiang
Published: May 2018

We experimentally studied unidirectional perfect absorbers with asymmetric sandwich structures composed of two thick metallic films with different thicknesses and a truncated symmetric photonic crystal (PC). Single-channel and multichannel near-perfect absorbers were obtained by adjusting period number of the PC. According to electromagnetic field intensity distributions at absorption wavelengths, the physical mechanism of near-perfect absorption derived from the coupling effect between optical Tamm state and Fabry-Pérot resonance. The unidirectional absorption phenomena were attributed to weak electric field distributions at absorption wavelengths for opposing directions of light incidence. The experimental values showed good agreement with theoretical results.
Uncertainty in forecasts of long-run economic growth
Authors: Christensen P. , Gillingham K. , Nordhaus W.
Published: May 2018

Significance

This study develops estimates of uncertainty in projections of global and regional per-capita economic growth rates through 2100, comparing estimates from expert forecasts and an econometric approach designed to analyze long-run trends and variability. Estimates from both methods indicate substantially higher uncertainty than is assumed in current studies of climate change impacts, damages, and adaptation. Results from this study suggest a greater than 35% probability that emissions concentrations will exceed those assumed in the most severe of the available climate change scenarios (RCP 8.5), illustrating particular importance for understanding extreme outcomes.
Amazonia is the primary source of Neotropical biodiversity
Authors: Antonelli Alexandre , Zizka Alexander , Carvalho Fernanda Antunes , Scharn Ruud , Bacon Christine D. , Silvestro Daniele , Condamine Fabien L.
Published: May 2018

Significance

Amazonia is not only the world’s most diverse rainforest but is also the region in tropical America that has contributed most to its total biodiversity. We show this by estimating and comparing the evolutionary history of a large number of animal and plant species. We find that there has been extensive interchange of evolutionary lineages among different regions and biomes, over the course of tens of millions of years. Amazonia stands out as the primary source of diversity, which can be mainly explained by the total amount of time Amazonian lineages have occupied the region. The exceedingly rich and heterogeneous diversity of the American tropics could only be achieved by high rates of dispersal events across the continent.
Socioeconomic status moderates age-related differences in the brain’s functional network organization and anatomy across the adult lifespan
Authors: Chan Micaela Y. , Na Jinkyung , Agres Phillip F. , Savalia Neil K. , Park Denise C. , Wig Gagan S.
Published: May 2018

Significance

An individual’s socioeconomic status (SES) is a central feature of their environmental surroundings and has been shown to relate to the development and maturation of their brain in childhood. Here, we demonstrate that an individual’s present (adult) SES relates to their brain function and anatomy across a broad range of middle-age adulthood. In middle-aged adults (35–64 years), lower SES individuals exhibit less organized functional brain networks and reduced cortical thickness compared with higher SES individuals. These relationships cannot be fully explained by differences in health, demographics, or cognition. Additionally, childhood SES does not explain the relation between SES and brain network organization. These observations provide support for a powerful relationship between the environment and the brain that is evident in adult middle age.
Pacing of Paleozoic macroevolutionary rates by Milankovitch grand cycles
Authors: Crampton James S. , Meyers Stephen R. , Cooper Roger A. , Sadler Peter M. , Foote Michael , Harte David
Published: May 2018

Significance

There has been long-standing debate about the relative roles of intrinsic biotic interactions vs. extrinsic environmental factors as drivers of biodiversity change. Here, we show that, relatively early in the history of complex life, Milankovitch “grand cycles” associated with astronomical rhythms explain between 9 and 16% of variation in species turnover probability (extinction probability plus speciation probability) in a major Early Paleozoic zooplankton group, the graptoloids. These grand cycles would have modulated climate variability, alternating times of relative stability in the environment with times of maximum volatility, which influenced oceanic circulation and structure and thus, phytoplankton populations at the base of the marine food web.
Methylglucosylation of aromatic amino and phenolic moieties of drug-like biosynthons by combinatorial biosynthesis
Authors: Xie Linan , Zhang Liwen , Wang Chen , Wang Xiaojing , Xu Ya-ming , Yu Hefen , Wu Ping , Li Shenglan , Han Lida , Gunatilaka A. A. Leslie , Wei Xiaoyi , Lin Min , Molnár István , Xu Yuquan
Published: May 2018

Significance

Glycosylation imparts improved pharmacokinetic and pharmacodynamic properties to many drug candidates. Here we identify the founding member of a new glycosyltransferase (GT) family from
Beauveria bassiana
that is not orthologous to GTs isolated from other fungi. This GT is clustered with a methyltransferase (MT) from a family hitherto characterized only from bacteria. This GT–MT biosynthetic module shows extensive promiscuity in conjugating methylglucose to structurally varied substrates, but yields products with substantial regio- and stereoselectivity. We demonstrate an efficient combinatorial biosynthetic platform to produce glycosylated polyketides unprecedented in nature, some with increased stability and bioactivity. We also use a biocatalytic platform to synthesize methylglucosides of flavonoids, anthraquinones, and naphthalenes, some with an
N
-glucosidic linkage not previously demonstrated with characterized fungal enzymes.
Spatial mutation patterns as markers of early colorectal tumor cell mobility
Authors: Ryser Marc D. , Min Byung-Hoon , Siegmund Kimberly D. , Shibata Darryl
Published: May 2018

Significance

Thanks to improved screening technologies, many small “premalignant” tumors are now detected and treated, which reduces late-stage disease and cancer mortality, but also leads to overdiagnosis. Indeed, it remains uncertain if the starts of benign and malignant tumors differ. Here, we combine mathematical multiscale models with multiregional sequencing to infer that the starts of benign and some malignant tumors differ. The abnormal cell mobility eventually needed for invasion and metastasis is already expressed at the start of growth for some malignant tumors but not benign tumors. Therefore, some malignant tumors start with more invasive potential (“born to be bad”), and this early abnormal cell mobility can potentially be used to identify patients more likely to benefit from aggressive treatment.
Weak Galilean invariance as a selection principle for coarse-grained diffusive models
Authors: Cairoli Andrea , Klages Rainer , Baule Adrian
Published: May 2018

Significance

Galilean invariance is a cornerstone of classical mechanics. It states that for closed systems the equations of motion of the microscopic degrees of freedom do not change under Galilean transformations to different inertial frames. However, the description of real world systems usually requires coarse-grained models integrating complex microscopic interactions indistinguishably as friction and stochastic forces, which intrinsically violate Galilean invariance. By studying the coarse-graining procedure in different frames, we show that alternative rules—denoted as “weak Galilean invariance”—need to be satisfied by these stochastic models. Our results highlight that diffusive models in general cannot be chosen arbitrarily based on the agreement with data alone but have to satisfy weak Galilean invariance for physical consistency.
Pseudomonas aeruginosa
transcriptome during human infection
Authors: Cornforth Daniel M. , Dees Justine L. , Ibberson Carolyn B. , Huse Holly K. , Mathiesen Inger H. , Kirketerp-Møller Klaus , Wolcott Randy D. , Rumbaugh Kendra P. , Bjarnsholt Thomas , Whiteley Marvin
Published: May 2018

Significance

Microbiologists typically use laboratory systems to study the bacteria that infect humans. Over time, this has created a gap between what researchers understand about bacteria growing in the laboratory and those growing in humans. It is well-known that the behavior of bacteria is shaped by their environment, but how this behavior differs in laboratory models compared with human infections is poorly understood. We compared transcription data from a variety of human infections with data from a range of in vitro samples. We found important differences in expression of genes involved in antibiotic resistance, cell–cell communication, and metabolism. Understanding the bacterial expression patterns in human patients is a necessary step toward improved therapy and the development of more accurate laboratory models.
Mapping the functional anatomy of Orai1 transmembrane domains for CRAC channel gating
Authors: Yeung Priscilla S.-W. , Yamashita Megumi , Ing Christopher E. , Pomès Régis , Freymann Douglas M. , Prakriya Murali
Published: May 2018

Significance

Store-operated Orai1 channels mediate transcriptional, proliferative, and effector-cell programs in many cells. Mutations in Orai1 that block channel activation or evoke constitutive channel activity are known to cause debilitating diseases in humans such as immunodeficiency, autoimmunity, myopathy, and thrombocytopenia. However, our understanding of the underlying molecular mechanisms of these diseases is limited by fundamental gaps in how Orai1 channels are gated. Here, we map key functional interactions between the transmembrane domains of Orai1 and identify several contacts that are critical for conveying the STIM1 gating signal to the pore. Our findings illuminate important allosteric interactions between topologically distinct domains of Orai1 and help elucidate the molecular underpinnings of disease-causing mutations.
A cytokine network involving IL-36γ, IL-23, and IL-22 promotes antimicrobial defense and recovery from intestinal barrier damage
Authors: Ngo Vu L. , Abo Hirohito , Maxim Estera , Harusato Akihito , Geem Duke , Medina-Contreras Oscar , Merlin Didier , Gewirtz Andrew T. , Nusrat Asma , Denning Timothy L.
Published: May 2018

Significance

Cytokines are produced in response to microbial threat and aid in the recruitment and activation of immune cells to protect the host. Using complementary in vitro and in vivo approaches, we have defined a cytokine network involving IL-36γ, IL-23, and IL-22 that is induced following intestinal damage and is critical for antimicrobial activity, tissue repair, and host survival. Our data identify IL-36γ/IL-36 receptor signaling as a central upstream driver of the IL-23/IL-22/antimicrobial peptide (AMP) pathway during intestinal injury and advance the concept that IL-36γ and IL-23 are fundamentally linked to repair of acute barrier damage. These findings provide new mechanistic insight into how the host commandeers proinflammatory cytokines for tissue repair and highlight the potential for manipulating the IL-36/IL-23/IL-22/AMP network in treating acute intestinal damage.
Comprehensive phylogeny of ray-finned fishes (Actinopterygii) based on transcriptomic and genomic data
Authors: Hughes Lily C. , Ortí Guillermo , Huang Yu , Sun Ying , Baldwin Carole C. , Thompson Andrew W. , Arcila Dahiana , Betancur-R. Ricardo , Li Chenhong , Becker Leandro , Bellora Nicolás , Zhao Xiaomeng , Li Xiaofeng , Wang Min , Fang Chao , Xie Bing , Zhou Zhuocheng , Huang Hai , Chen Songlin , Venkatesh Byrappa , Shi Qiong
Published: May 2018

Significance

Ray-finned fishes form the largest and most diverse group of vertebrates. Establishing their phylogenetic relationships is a critical step to explaining their diversity. We compiled the largest comparative genomic database of fishes that provides genome-scale support for previous phylogenetic results and used it to resolve further some contentious relationships in fish phylogeny. A vetted set of exon markers identified in this study is a promising resource for current sequencing approaches to significantly increase genetic and taxonomic coverage to resolve the tree of life for all fishes. Our time-calibrated analysis suggests that most lineages of living fishes were already established in the Mesozoic Period, more than 65 million years ago.
AtPep3 is a hormone-like peptide that plays a role in the salinity stress tolerance of plants
Authors: Nakaminami Kentaro , Okamoto Masanori , Higuchi-Takeuchi Mieko , Yoshizumi Takeshi , Yamaguchi Yube , Fukao Yoichiro , Shimizu Minami , Ohashi Chihiro , Tanaka Maho , Matsui Minami , Shinozaki Kazuo , Seki Motoaki , Hanada Kousuke
Published: May 2018

Significance

Hormone-like peptides derived from small coding genes (<100 amino acids) have not been extensively characterized in relation to abiotic stress tolerance. Focusing on 17 salinity stress-inducible small coding genes in
Arabidopsis
, we showed that four genes conferred increased salinity stress tolerance when overexpressed in transgenic plants. One of the four genes (
AtPROPEP3
) was found to induce salinity stress tolerance by treatment with a 13-peptide (KPTPSSGKGGKHN) fragment, providing unique functional evidence for enhanced salinity stress tolerance in plants in response to a peptide treatment. Although the 13-peptide fragment shares homology with known peptides associated with immune response, the other peptides may encode unique hormone-like peptides associated with salinity stress tolerance.
Endocast morphology of
Homo naledi
from the Dinaledi Chamber, South Africa
Authors: Holloway Ralph L. , Hurst Shawn D. , Garvin Heather M. , Schoenemann P. Thomas , Vanti William B. , Berger Lee R. , Hawks John
Published: May 2018

Significance

The new species
Homo naledi
was discovered in 2013 in a remote cave chamber of the Rising Star cave system, South Africa. This species survived until between 226,000 and 335,000 y ago, placing it in continental Africa at the same time as the early ancestors of modern humans were arising. Yet,
H. naledi
was strikingly primitive in many aspects of its anatomy, including the small size of its brain. Here, we have provided a description of endocast anatomy of this primitive species. Despite its small brain size,
H. naledi
shared some aspects of human brain organization, suggesting that innovations in brain structure were ancestral within the genus
Homo
.
Cochlear amplification and tuning depend on the cellular arrangement within the organ of Corti
Authors: Motallebzadeh Hamid , Soons Joris A. M. , Puria Sunil
Published: May 2018

Significance

While the near-crystalline structure of the organ-of-Corti cytoarchitecture in the mammalian cochlea has been known for some time, its functional consequences on hearing remain to be established. The present computational-modeling studies show that individual outer hair cells (OHCs) can work together to produce high hearing sensitivity and frequency selectivity because of the overlapping asymmetrical Y-shaped structures that they form with the Deiters’ cells (DCs) and phalangeal processes (PhPs). Altering the geometry and material properties of these structures reveals that all three components have a profound effect on basilar-membrane and reticular-lamina amplification and tuning. One implication is that the DCs and PhPs are not just supporting structures, but that they must also be properly restored in emerging therapies to regenerate OHCs.
Lead pollution recorded in Greenland ice indicates European emissions tracked plagues, wars, and imperial expansion during antiquity
Authors: McConnell Joseph R. , Wilson Andrew I. , Stohl Andreas , Arienzo Monica M. , Chellman Nathan J. , Eckhardt Sabine , Thompson Elisabeth M. , Pollard A. Mark , Steffensen Jørgen Peder
Published: May 2018

Significance

An 1100 BCE to 800 CE record of estimated lead emissions based on continuous, subannually resolved, and precisely dated measurements of lead pollution in deep Greenland ice and atmospheric modeling shows that European emissions closely varied with historical events, including imperial expansion, wars, and major plagues. Emissions rose coeval with Phoenician expansion and accelerated during expanded Carthaginian and Roman lead–silver mining primarily in the Iberian Peninsula. Emissions fluctuated synchronously with wars and political instability, particularly during the Roman Republic, reaching a sustained maximum during the Roman Empire before plunging in the second century coincident with the Antonine plague, and remaining low for >500 years. Bullion in silver coinage declined in parallel, reflecting the importance of lead–silver mining in ancient economies.
Why we need to look beyond the glass transition temperature to characterize the dynamics of thin supported polymer films
Authors: Zhang Wengang , Douglas Jack F. , Starr Francis W.
Published: May 2018

Significance

The disparate results for

T

g

shifts of polymer thin films raise the question of whether

T

g

provides a good metric to characterize changes in the overall dynamics of these films. Our work demonstrates how different techniques to measure

T

g

are influenced by the relaxation gradient across the film. We find that different measurement methods can provide contradictory

T

g

estimates, depending on their sensitivity to dynamics near the substrate, providing a possible explanation for prior contradictory results. We take advantage of these differences by combining

T

g

estimates to predict

T

g

near the substrate. Our findings should be useful for polymer thin film applications, including microelectronic devices, lithium battery technology, and the development of biomedical devices.
The glycolipid GM1 reshapes asymmetric biomembranes and giant vesicles by curvature generation
Authors: Dasgupta Raktim , Miettinen Markus S. , Fricke Nico , Lipowsky Reinhard , Dimova Rumiana
Published: May 2018

Significance

The multifaceted involvement of GM1 as a ligand in many cellular functions has been well recognized. We find that GM1 readily desorbs from the membrane of cell-sized model biomimetic systems (giant unilamellar vesicles). The desorption is unbalanced, creating an asymmetry between the bilayer leaflets. This results in reshaping weakly curved membranes into nanotubular invaginations stabilized by the membrane spontaneous curvature, which we quantify experimentally. Computer simulations confirm the experimental results. Uncovering the role of GM1 as a fine regulator of membrane curvature broadens our perspective on its important function in reshaping neuronal membranes and emphasizes that GM1 desorption can strongly affect the cell membrane morphology.
Additive-free carbon nanotube dispersions, pastes, gels, and doughs in cresols
Authors: Chiou Kevin , Byun Segi , Kim Jaemyung , Huang Jiaxing
Published: May 2018

Significance

Carbon nanotubes can now be produced in the ton scale in the form of powders, but they need to be further processed, usually by solution-based routes, into disaggregated and more usable forms for applications. There has been extensive effort to search and design solvents that can disperse nanotubes, which can also be easily removed afterward. Here, we report thatm-cresol and its liquid mixtures with other isomers, which are already manufactured for other industrial purposes, are such solvents. They can disperse carbon nanotube powders of many types at unprecedentedly high concentrations, rendering them polymer-like rheological and viscoelastic properties, and high processability. This makes carbon nanotube powders immediately usable by current materials-processing techniques for creating desirable structures or composites.
Corticoinsular circuits encode subjective value expectation and violation for effortful goal-directed behavior
Authors: Arulpragasam Amanda R. , Cooper Jessica A. , Nuutinen Makiah R. , Treadway Michael T.
Published: May 2018

Significance

The ability to form value estimates is crucial for optimal decision making, especially when not all features of a choice option are known. To date, however, the neural mechanisms for expectation processes under conditions of incomplete information are unknown. Using computational fMRI, we show that ventromedial prefrontal cortex encodes the expected value of a trial. We also observe a distinct network composed of dorsal anterior cingulate, anterior insula, and dorsomedial caudate that encodes an expectation violation or prediction error signal, based on previous trial history. These findings highlight how the brain computes and monitors value-based predictions during effortful goal-directed behavior when choice-relevant information is not fully available.
Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by
Staphylococcus aureus
and supports fracture healing
Authors: Johnson Christopher T. , Wroe James A. , Agarwal Rachit , Martin Karen E. , Guldberg Robert E. , Donlan Rodney M. , Westblade Lars F. , García Andrés J.
Published: May 2018

Significance

Orthopedic implant infections require long-term antibiotic therapy and surgical debridement to successfully retain the implant; however, therapeutic failure can lead to implant removal. Here an injectable PEG-based hydrogel that adheres to exposed tissue and fracture surfaces is engineered to deliver the antimicrobial enzyme lysostaphin to infected, implant-fixed, mouse femoral fractures. Lysostaphin encapsulation within the hydrogel enhances enzyme stability while providing enhanced antibiofilm activity and serving as a controlled delivery platform. In a preclinical animal model of orthopedic-implant infection, we show that lysostaphin-delivering hydrogels outperform prophylactic antibiotic therapy and soluble lysostaphin, by eradicating infection while promoting bone repair. Importantly, lysostaphin-delivering hydrogels are effective against antibiotic-resistant infections. This lysostaphin delivery platform could be highly effective at treating and preventing implant infections.
Chaperone AMPylation modulates aggregation and toxicity of neurodegenerative disease-associated polypeptides
Authors: Truttmann Matthias C. , Pincus David , Ploegh Hidde L.
Published: May 2018

Significance

Protein AMPylation in eukaryotes is a comparatively understudied posttranslational modification. With the exception of yeast, all eukaryotes have the enzymatic machinery required to execute this modification. Members of the heat shock protein family in different cellular compartments appear to be preferred targets for AMPylation, but it has proven challenging to adduce its biological function. We show that genetic modifications that affect AMPylation status, through generation of null alleles and a constitutively active version of the AMPylase FIC-1, can have a major impact on the susceptibility of
Caenorhabditis elegans
to neurodegenerative conditions linked to protein aggregation.
Heterometallic Ru–Pt metallacycle for two-photon photodynamic therapy
Authors: Zhou Zhixuan , Liu Jiangping , Rees Thomas W. , Wang Heng , Li Xiaopeng , Chao Hui , Stang Peter J.
Published: May 2018

Significance

Photodynamic therapy is a noninvasive medical procedure in which malignant tissue is damaged by reactive oxygen species generated from targeted light irradiation on a photosensitizer. Herein, we incorporate an Ru(II)-based two-photon photosensitizer into a macrocyclic structure via coordination-driven self-assembly. Properties favorable for photodynamic therapy arise upon formation of the metallacycle, including near-infrared luminescence, strong two-photon absorption, high reactive oxygen species generation efficiency, and selective accumulation in mitochondria and nucleus that are hypersensitive to reactive oxygen species, resulting in good photodynamic therapy efficacy in both in vitro and in vivo investigations. This study shows that supramolecular coordination complexes provide a platform for efficient tuning on the photophysical and biological properties of molecules with biomedical interest.
Noncatalytic chalcone isomerase-fold proteins in
Humulus lupulus
are auxiliary components in prenylated flavonoid biosynthesis
Authors: Ban Zhaonan , Qin Hao , Mitchell Andrew J. , Liu Baoxiu , Zhang Fengxia , Weng Jing-Ke , Dixon Richard A. , Wang Guodong
Published: May 2018

Significance

Here, we identify two noncatalytic chalcone isomerase-fold proteins, which are critical for high-efficiency prenylchalcone production in
Humulus lupulus
. Our results provide insights into their evolutionary development from the ancestral noncatalytic fatty acid-binding chalcone isomerase-fold proteins to specialized auxiliary proteins supporting flavonoid biosynthesis in plants, and open up the possibility of producing high-value plant prenylchalcones using heterologous systems.
Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility
Authors: Li Wentao , Hulswit Ruben J. G. , Kenney Scott P. , Widjaja Ivy , Jung Kwonil , Alhamo Moyasar A. , van Dieren Brenda , van Kuppeveld Frank J. M. , Saif Linda J. , Bosch Berend-Jan
Published: May 2018

Significance

Coronaviruses exhibit a propensity for interspecies transmission, with SARS- and MERS-coronaviruses as notable examples. Cross-species transmission by coronaviruses is foremost determined by the virus’ ability to bind receptors of new hosts. We here report that the recently identified, yet globally distributed porcine deltacoronavirus employs host aminopeptidase N (APN) as an entry receptor via S protein-mediated interaction with an interspecies conserved domain that allows for APN orthologue-mediated entry. Identification of APN as a deltacoronavirus receptor emphasizes the remarkable preferential employment of cell surface host peptidases as receptors by coronaviruses. Our findings provide important insight into how receptor usage of coronaviruses may fuel cross-host transmission between distantly related species and necessitate surveillance studies of deltacoronaviruses in thus far unappreciated potential reservoirs, including humans.
PRDM1 silences stem cell-related genes and inhibits proliferation of human colon tumor organoids
Authors: Liu Changlong , Banister Carolyn E. , Weige Charles C. , Altomare Diego , Richardson Joseph H. , Contreras Carlo M. , Buckhaults Phillip J.
Published: May 2018

Significance

Our previous studies demonstrated that PRDM1β is activated by p53 accumulation in human colorectal cancer cells. However, the function of PRDM1β in colorectal cancer cells and colon tumor organoids is not clear. Here we show that PRDM1β is a p53-response gene in human colon organoids and that low PRDM1 expression predicts poor survival in colon cancer patients. Also, PRDM1α and PRDM1β proteins repress a largely overlapping suite of genes, many of which are stem cell-related genes. Moreover, we show that forced expression of PRDM1β prevents the proliferation of colon tumor organoids. This work provides support for a role of PRDM1β in regulating normal colon stem cell proliferation.
Elastic coupling power stroke mechanism of the F
1
-ATPase molecular motor
Authors: Martin James L. , Ishmukhametov Robert , Spetzler David , Hornung Tassilo , Frasch Wayne D.
Published: May 2018

Significance

Molecular motor F
1
-ATPases use the free energy from ATP binding and hydrolysis to ADP and Pi to rotate subunit γ, and can synthesize ATP in the F
O
F
1
ATP synthase. We determined the energetics during each 3° of the power stroke from temperature-dependent changes of angular velocity. Unexpectedly, the power stroke activation energy of phase 1 (0°–60°) was negative and varied parabolically, indicating that it was powered by elastic energy of a torsional spring consistent with unwinding the γ-subunit coiled-coil. Phase 2 rotation had an enthalpic component, indicating additional input of energy is required to complete the 120° power stroke, consistent with energy derived from ATP binding. These results deepen our understanding of these important molecular motors summarized in the proposed elastic coupling mechanism.
Temperature regulates NF-κB dynamics and function through timing of A20 transcription
Authors: Harper C. V. , Woodcock D. J. , Lam C. , Garcia-Albornoz M. , Adamson A. , Ashall L. , Rowe W. , Downton P. , Schmidt L. , West S. , Spiller D. G. , Rand D. A. , White M. R. H.
Published: May 2018

Significance

Inflammation is often accompanied by temperature change, but little is known about the role of temperature in the inflammatory response. We show that physiologically relevant temperature changes significantly perturb NF-κB dynamics following TNFα stimulation in single cells. Using experimentation informed by mathematical modeling, we found that these changes were mediated, at least in part, through the key feedback gene TNFAIP3/A20. Curtailing A20 expression removed temperature sensitivity across the fever range (37 °C to 40 °C). Gene expression was generally unaffected between these temperatures, although a select set of NF-κB−regulated genes was up-regulated at early time points. These genes were predominantly involved in inflammation, signaling, and cell fate. The cellular response to inflammation may therefore be mechanistically and functionally regulated by temperature.
Adjective stacking in Early Modern English
Authors: González-Díaz Victorina
Published: May 2018

Previous scholarship dates the development of stacked modification in English to the late Middle English period and the operationalisation of the modern NP functional structure to the end of the seventeenth century (Fischer 2006; Feist 2012). These studies have mainly focused on linguistic factors playing a role in the change, although observing briefly that socio-stylistic considerations also play a role in the development of stacked strings. Through a descriptive, corpus-based study of two-adjective strings in early Modern English, this paper begins to explore the influence of socio-stylistic matters on the change. The results suggest that the functional-stylistic demands of written genres may have favoured the establishment of particular stacked strings in English and this paper argues for a careful consideration of ‘developing’ genres in early Modern English (especially travelogues) as an important locus of change in the evolution of the English premodifying string.
That-complementiser omission in N + be + that-clauses
Authors: Mantlik Annette , Schmid Hans-Jörg
Published: May 2018

The omission of the complementiser that after lexical verbs, as in I think she went home or I guess she did not enjoy herself, has been studied intensively from a diachronic and synchronic perspective. In contrast, that-complementiser omission in other contexts (e.g. the truth is she never wanted to come anyway or the problem is she does not like these people) has not received much attention. We report the results of a multi-level corpus-based study investigating the diachronic development of the omission of that in the N + BE + that construction. The study is framed in the light of two competing hypotheses suggested by research on that-omission in verb complementation: the assumption that the omission is mainly a matter of stylistic choice and the assumption that it represents a case of diachronic change that can be described as constructional change or even constructionalisation. In order to test these hypotheses, we carry out a quantitative and qualitative analysis of a large dataset extracted from the Corpus of Historical American English. The results suggest that both factors are involved but shift in importance over time. While stylistic choice may have been the original motivation for the omission of that, the later development shows evidence for constructional change and signs indicating the beginning of further changes that could eventually lead to the emergence of a new construction by means of constructional split.
Metabolic regulation of chromatin modifications and gene expression
Authors: Schvartzman Juan Manuel , Thompson Craig B. , Finley Lydia W.S.
Published: May 2018

Dynamic regulation of gene expression in response to changing local conditions is critical for the survival of all organisms. In metazoans, coherent regulation of gene expression programs underlies the development of functionally distinct cell lineages. The cooperation between transcription factors and the chromatin landscape enables precise control of gene expression in response to cell-intrinsic and cell-extrinsic signals. Many of the chemical modifications that decorate DNA and histones are adducts derived from intermediates of cellular metabolic pathways. In addition, several of the enzymes that can remove these marks use metabolites as part of their enzymatic reaction. These observations have led to the hypothesis that fluctuations in metabolite levels influence the deposition and removal of chromatin modifications. In this review, we consider the emerging evidence that cellular metabolic activity contributes to gene expression and cell fate decisions through metabolite-dependent effects on chromatin organization.
The association between discrimination and health: findings on Russian, Somali and Kurdish origin populations in Finland
Authors: Rask Shadia , Elo Irma T , Koskinen Seppo , Lilja Eero , Koponen Päivikki , Castaneda Anu E
Published: May 2018

Background

The Second European Union Minorities and Discrimination Survey recently demonstrated widespread discrimination across EU countries, with high discrimination rates observed in countries like Finland. Discrimination is known to negatively impact health, but fewer studies have examined how different types of perceived discrimination are related to health.

Methods

This study examines (i) the prevalence of different types of perceived discrimination among Russian, Somali and Kurdish origin populations in Finland, and (ii) the association between different types of perceived discrimination (no experiences; subtle discrimination only; overt or subtle and overt discrimination) and health (self-rated health; limiting long-term illness (LLTI) or disability; mental health symptoms). Data are from the Finnish Migrant Health and Wellbeing Study (n = 1795). Subtle discrimination implies reporting being treated with less courtesy and/or treated with less respect than others, and overt discrimination being called names or insulted and/or threatened or harassed. The prevalence of discrimination and the associations between discrimination and health were calculated with predicted margins and logistic regression.

Results

Experiences of subtle discrimination were more common than overt discrimination in all the studied groups. Subtle discrimination was reported by 29% of Somali origin persons and 35% Russian and Kurdish origin persons. The prevalence of overt discrimination ranged between 22% and 24%. Experiences of discrimination increased the odds for poor self-reported health, LLTI and mental health symptoms, particularly among those reporting subtle discrimination only.

Conclusions

To promote the health of diverse populations, actions against racism and discrimination are highly needed, including initiatives that promote shared belonging.
Physical activity promotion in primary care: a Utopian quest?
Authors: Lion Alexis , Vuillemin Anne , Thornton Jane S , Theisen Daniel , Stranges Saverio , Ward Malcolm
Published: May 2018

The health benefits of physical activity (PA) are acknowledged and promoted by the scientific community, especially within primary care. However, there is little evidence that such promotion is provided in any consistent or comprehensive format. Brief interventions (i.e. discussion, negotiation or encouragement) and exercise referral schemes (i.e. patients being formally referred to a PA professional) are the two dominant approaches within primary care. These cost-effective interventions can generate positive changes in health outcomes and PA levels in inactive patients who are at increased risk for non-communicable diseases. Their success relies on the acceptability and efficiency of primary care professionals to deliver PA counselling. To this end, appropriate training and financial support are crucial. Similarly, human resourcing and synergy between the different stakeholders must be addressed. To obtain maximum adherence, specific populations should be targeted and interventions adapted to their needs. Key enablers include motivational interviewing, social support and multi-disciplinary approaches. Leadership and lines of accountability must be clearly delineated to ensure the success of the initiatives promoting PA in primary care. The synergic and multisectoral action of several stakeholders, especially healthcare professionals, will help overcome physical inactivity in a sustainable way.
The adoption, implementation and maintenance of a school food policy in the Canadian Arctic: a retrospective case study
Authors: Fournier Bonnie , Illasiak Velma , Kushner Kaysi Eastlick , Raine Kim
Published: May 2018

With increasing childhood obesity rates and type 2 diabetes developing in younger age groups, many schools have initiated policies to support healthy eating and active living. Policy interventions can influence not only health behaviours in students but can also impact these behaviours beyond the school walls into the community. We articulate a policy story that emerged during the data collection phase of a study focused on building knowledge and capacity to support healthy eating and active living policy options in a small hamlet located in the Canadian Arctic. The policy processes of a local school food policy to address unhealthy eating are discussed. Through 14 interviews, decision makers, policy influencers and health practitioners described a policy process, retrospectively, including facilitators and barriers to adopting and implementing policy. A number of key activities facilitated the successful policy implementation process and the building of a critical mass to support healthy eating and active living in the community. A key contextual factor in school food policies in the Arctic is the influence of traditional (country) foods. This study is the first to provide an in-depth examination of the implementation of a food policy in a Canadian Arctic school. Recommendations are offered to inform intervention research and guide a food policy implementation process in a school environment facing similar issues.
Introduction to Methodology: Virtual Special Issue for the Journal of Design History 2018
Authors: Huppatz D J
Published: May 2018

Design historians generally avoid extended self-reflection or discussion of how they conduct research. Typically, they use historical research methods, yet design historians have also used methods borrowed from art history, cultural and literary studies, anthropology, sociology or other social sciences. This Virtual Special Issue, comprising articles drawn from past issues of the Journal of Design History, addresses the state of design history’s methodology. While few authors in the Journal have focused specifically on the topic of methodology, their implicit adoption of an eclectic variety of research methods over the past thirty years is revealing. This Introduction seeks to contextualize a collection of twelve articles within a brief overview of methodologies in history, art history and design history. The articles are then linked to scholarship beyond the Journal of Design History, and the final section presents additional methodological possibilities for design historians.
Radiation Exposure From Pediatric CT Scans and Subsequent Cancer Risk in the Netherlands
Authors: Meulepas Johanna M , Ronckers Cécile M , Smets Anne M J B , Nievelstein Rutger A J , Gradowska Patrycja , Lee Choonsik , Jahnen Andreas , van Straten Marcel , de Wit Marie-Claire Y , Zonnenberg Bernard , Klein Willemijn M , Merks Johannes H , Visser Otto , van Leeuwen Flora E , Hauptmann Michael
Published: May 2018

Background

Computed tomography (CT), a strong diagnostic tool, delivers higher radiation doses than most imaging modalities. As CT use has increased rapidly, radiation protection is important, particularly among children. We evaluate leukemia and brain tumor risk following exposure to low-dose ionizing radiation from CT scans in childhood.

Methods

For a nationwide retrospective cohort of 168 394 children who received one or more CT scans in a Dutch hospital between 1979 and 2012 who were younger than age 18 years, we obtained cancer incidence, vital status, and confounder information by record linkage with external registries. Standardized incidence ratios were calculated using cancer incidence rates from the general Dutch population. Excess relative risks (ERRs) per 100 mGy organ dose were calculated with Poisson regression. All statistical tests were two-sided.

Results

Standardized incidence ratios were elevated for all cancer sites. Mean cumulative bone marrow doses were 9.5 mGy at the end of follow-up, and leukemia risk (excluding myelodysplastic syndrome) was not associated with cumulative bone marrow dose (44 cases). Cumulative brain dose was on average 38.5 mGy and was statistically significantly associated with risk for malignant and nonmalignant brain tumors combined (ERR/100 mGy: 0.86, 95% confidence interval = 0.20 to 2.22, P = .002, 84 cases). Excluding tuberous sclerosis complex patients did not substantially change the risk.

Conclusions

We found evidence that CT-related radiation exposure increases brain tumor risk. No association was observed for leukemia. Compared with the general population, incidence of brain tumors was higher in the cohort of children with CT scans, requiring cautious interpretation of the findings.
Sgr A* envelope explosion and the young stars in the centre of the Milky Way
Authors: Nayakshin Sergei , Zubovas Kastytis
Published: May 2018

Sgr A* is the supermassive black hole residing in the centre of the Milky Way. There is plenty of observational evidence that a massive gas cloud fell into the central parsec of the Milky Way ∼6 Myr ago, triggering formation of a disc of young stars and activating Sgr A*. In addition to the disc, there is an unexplained population of young stars on randomly oriented orbits. Here we hypothesize that these young stars were formed by fragmentation of a massive quasi-spherical gas shell driven out from Sgr A* potential well by an energetic outflow. To account for the properties of the observed stars, the shell must be more massive than 105 solar masses, be launched from inside ∼0.01 pc, and the feedback outflow has to be highly super-Eddington albeit for a brief period of time, producing kinetic energy of at least 1055 erg. The young stars in the central parsec of the Galaxy may be a unique example of stars formed from atomic rather than molecular hydrogen, and forged by extreme pressure of black hole outflows.
Oncolytic virotherapy in glioblastoma patients induces a tumor macrophage phenotypic shift leading to an altered glioblastoma microenvironment
Authors: van den Bossche Wouter B L , Kleijn Anne , Teunissen Charlotte E , Voerman Jane S A , Teodosio Cristina , Noske David P , van Dongen Jacques J M , Dirven Clemens M F , Lamfers Martine L M
Published: May 2018

Background

Immunosuppressive protumoral M2 macrophages are important in pathogenesis, progression, and therapy resistance in glioblastoma (GBM) and provide a target for therapy. Recently oncolytic virotherapy in murine models was shown to change these M2 macrophages toward the pro-inflammatory and antitumoral M1 phenotype. Here we study the effects of the oncolytic virotherapy Delta24-RGD in humans, using both in vitro models and patient material.

Methods

Human monocyte-derived macrophages were co-cultured with Delta24-RGD–infected primary glioma stem-like cells (GSCs) and were analyzed for their immunophenotype, cytokine expression, and secretion profiles. Cerebrospinal fluid (CSF) from 18 Delta24-RGD–treated patients was analyzed for inflammatory cytokine levels, and the effects of these CSF samples on macrophage phenotype in vitro were determined. In addition, tumor macrophages in resected material from a Delta24-RGD–treated GBM patient were compared with 5 control GBM patient samples by flow cytometry.

Results

Human monocyte-derived M2 macrophages co-cultured with Delta24-RGD–infected GSCs shifted toward an M1-immunophenotype, coinciding with pro-inflammatory gene expression and cytokine production. This phenotypic switch was induced by the concerted effects of a change in tumor-produced soluble factors and the presence of viral particles. CSF samples from Delta24-RGD–treated GBM patients revealed cytokine levels indicative of a pro-inflammatory microenvironment. Furthermore, tumoral macrophages in a Delta24-RGD–treated patient showed significantly greater M1 characteristics than in control GBM tissue.

Conclusion

Together these in vitro and patient studies demonstrate that local Delta24-RGD therapy may provide a therapeutic tool to promote a prolonged shift in the protumoral M2 macrophages toward M1 in human GBM, inducing a pro-inflammatory and potentially tumor-detrimental microenvironment.
On the colour variations of negative superhumps
Authors: Imada Akira , Yanagisawa Kenshi , Kawai Nobuyuki
Published: May 2018

We present simultaneous g΄, Rc, and Ic photometry of the notable dwarf nova ER UMa during the 2011 season. Our photometry revealed that the brightness maxima of negative superhumps coincide with the bluest peaks in g΄ − Ic colour variations. We also found that the amplitudes of negative superhumps are the largest in the g΄ band. These observed properties are significantly different from those observed in early and positive superhumps. Our findings are consistent with a tilted disk model as the light source of negative superhumps.
Knowledge Discovery and Data Mining
Authors: Clancy Thomas Roy , Gelinas Lillee
Published: May 2018

As systems evolve, their tendency is to become more complex. Studies in the field of complex systems have generated new perspectives on the application of management strategies in health systems. This is the 2nd in a series of articles addressing the mounting challenges faced by nursing leaders demanding insights from the vast amounts of information collected and stored by their organizations.
Understanding Mentorship in a Research Training Program for Point-of-Care Clinicians
Authors: Black Agnes T. , Bungay Vicky , Mackay Martha , Balneaves Lynda G. , Garossino Candy
Published: May 2018

Evidence-based practice (EBP) is essential to high-quality patient care and can contribute to healthcare cost savings, yet nurses and other clinicians at the point of care report barriers to engagement with research and translating it to the clinical setting. Mentorship has been shown to improve nurses’ understanding and implementation of EBP. In this article, we describe a mentorship model in a successful program to support point-of-care nurses in conducting small-scale research projects, many of which have led to practice changes and/or cost savings.