bluuebunny/crossref_metadata_2025 huggingface dataset:
800 years on can Magna Carta still disrupt the executive?
Authors: Moss Michael
Published: July 2016

In June 1215 King John put his seal to Magna Carta, which over the centuries has become an icon of English (British) liberties. Clause 40 about not selling, denying or delaying justice, and Clause 39, that no free man is to be imprisoned or dispossessed “save by the lawful judgment of his peers or by the law of the land” are still in force today. For these reasons Lord Denning described Magna Carta as “the greatest constitutional document of all times—the foundation of the freedom of the individual against the arbitrary authority of the despot”. In other words the executive can never be above the law, but for this principle to be enforced the state must disclose evidence by due process to the public by which it can be held to account. This essay explores the threats to openness of government in the digital age, which runs the risk of undermining this fundamental principle of the British constitution. These range from the intrusiveness of our surveillance society, ill-considered notions of a post-privacy world, misconceived concepts of open data to the immense difficulty of scrutinizing born-digital data released under due process for sensitive content. Such threats are balanced by a much more assertive judiciary under the supreme court, which like its American counterpart strikes down legislation, an unelected second chamber willing to challenge the executive and House of Commons select committees that are increasingly baring their teeth. This article is published as part of a collection entitled ‘IT as a utility’.
Resynchronization of circadian oscillators and the east-west asymmetry of jet-lag
Authors: Lu Zhixin , Klein-Cardeña Kevin , Lee Steven , Antonsen Thomas M. , Girvan Michelle , Ott Edward
Published: July 2016

Cells in the brain's Suprachiasmatic Nucleus (SCN) are known to regulate circadian rhythms in mammals. We model synchronization of SCN cells using the forced Kuramoto model, which consists of a large population of coupled phase oscillators (modeling individual SCN cells) with heterogeneous intrinsic frequencies and external periodic forcing. Here, the periodic forcing models diurnally varying external inputs such as sunrise, sunset, and alarm clocks. We reduce the dimensionality of the system using the ansatz of Ott and Antonsen and then study the effect of a sudden change of clock phase to simulate cross-time-zone travel. We estimate model parameters from previous biological experiments. By examining the phase space dynamics of the model, we study the mechanism leading to the difference typically experienced in the severity of jet-lag resulting from eastward and westward travel.
Synthesis of graphene and graphene nanostructures by ion implantation and pulsed laser annealing
Authors: Wang Xiaotie , Berke Kara , Rudawski Nicholas G. , Venkatachalam Dinesh K. , Elliman Robert G. , Fridmann Joel , Hebard Arthur F. , Ren Fan , Gila Brent P. , Appleton Bill R.
Published: July 2016

In this paper, we report a systematic study that shows how the numerous processing parameters associated with ion implantation (II) and pulsed laser annealing (PLA) can be manipulated to control the quantity and quality of graphene (G), few-layer graphene (FLG), and other carbon nanostructures selectively synthesized in crystalline SiC (c-SiC). Controlled implantations of Si− plus C− and Au+ ions in c-SiC showed that both the thickness of the amorphous layer formed by ion damage and the doping effect of the implanted Au enhance the formation of G and FLG during PLA. The relative contributions of the amorphous and doping effects were studied separately, and thermal simulation calculations were used to estimate surface temperatures and to help understand the phase changes occurring during PLA. In addition to the amorphous layer thickness and catalytic doping effects, other enhancement effects were found to depend on other ion species, the annealing environment, PLA fluence and number of pulses, and even laser frequency. Optimum II and PLA conditions are identified and possible mechanisms for selective synthesis of G, FLG, and carbon nanostructures are discussed.
Aerodynamic levitator for in situ x-ray structure measurements on high temperature and molten nuclear fuel materials
Authors: Weber J. K. R. , Tamalonis A. , Benmore C. J. , Alderman O. L. G. , Sendelbach S. , Hebden A. , Williamson M. A.
Published: July 2016

An aerodynamic levitator with carbon dioxide laser beam heating was integrated with a hermetically sealed controlled atmosphere chamber and sample handling mechanism. The system enabled containment of radioactive samples and control of the process atmosphere chemistry. The chamber was typically operated at a pressure of approximately 0.9 bars to ensure containment of the materials being processed. Samples 2.5-3 mm in diameter were levitated in flowing gas to achieve containerless conditions. Levitated samples were heated to temperatures of up to 3500 °C with a partially focused carbon dioxide laser beam. Sample temperature was measured using an optical pyrometer. The sample environment was integrated with a high energy (100 keV) x-ray synchrotron beamline to enable in situ structure measurements to be made on levitated samples as they were heated, melted, and supercooled. The system was controlled from outside the x-ray beamline hutch by using a LabVIEW program. Measurements have been made on hot solid and molten uranium dioxide and binary uranium dioxide-zirconium dioxide compositions.
Comparative investigation of surface transfer doping of hydrogen terminated diamond by high electron affinity insulators
Authors: Verona C. , Ciccognani W. , Colangeli S. , Limiti E. , Marinelli Marco , Verona-Rinati G.
Published: July 2016

We report on a comparative study of transfer doping of hydrogenated single crystal diamond surface by insulators featured by high electron affinity, such as Nb2O5, WO3, V2O5, and MoO3. The low electron affinity Al2O3 was also investigated for comparison. Hole transport properties were evaluated in the passivated hydrogenated diamond films by Hall effect measurements, and were compared to un-passivated diamond films (air-induced doping). A drastic improvement was observed in passivated samples in terms of conductivity, stability with time, and resistance to high temperatures. The efficiency of the investigated insulators, as electron accepting materials in hydrogenated diamond surface, is consistent with their electronic structure. These surface acceptor materials generate a higher hole sheet concentration, up to 6.5 × 1013 cm−2, and a lower sheet resistance, down to 2.6 kΩ/sq, in comparison to the atmosphere-induced values of about 1 × 1013 cm−2 and 10 kΩ/sq, respectively. On the other hand, hole mobilities were reduced by using high electron affinity insulator dopants. Hole mobility as a function of hole concentration in a hydrogenated diamond layer was also investigated, showing a well-defined monotonically decreasing trend.
On the role of diluted magnetic cobalt-doped ZnO electrodes in efficiency improvement of InGaN light emitters
Authors: Liu Hong-Ru , Ou Sin-Liang , Wang Shih-Yin , Wuu Dong-Sing
Published: July 2016

The 120-nm-thick cobalt-doped ZnO (Co-doped ZnO, CZO) dilute magnetic films deposited by pulsed laser deposition were employed as the n-electrodes for both lateral-type blue (450 nm) and green (520 nm) InGaN light emitters. In comparison to the conventional blue and green emitters, there were 15.9% and 17.7% enhancements in the output power (@350 mA) after fabricating the CZO n-electrode on the n-GaN layer. Observations on the role of CZO n-electrodes in efficiency improvement of InGaN light emitters were performed. Based on the results of Hall measurements, the carrier mobilities were 176 and 141 cm2/V s when the electrons passed through the n-GaN and the patterned-CZO/n-GaN, respectively. By incorporating the CZO n-electrode into the InGaN light emitters, the electrons would be scattered because of the collisions between the magnetic atoms and the electrons as the device is driven, leading to the reduction of the electron mobility. Therefore, the excessively large mobility difference between electron and hole carriers occurred in the conventional InGaN light emitter can be efficiently decreased after preparing the CZO n-electrode on the n-GaN layer, resulting in the increment of carrier recombination rate and the improvement of light output power.
Polycrystalline silicon carbide dopant profiles obtained through a scanning nano-Schottky contact
Authors: Golt M. C. , Strawhecker K. E. , Bratcher M. S. , Shanholtz E. R.
Published: July 2016

The unique thermo-electro-mechanical properties of polycrystalline silicon carbide (poly-SiC) make it a desirable candidate for structural and electronic materials for operation in extreme environments. Necessitated by the need to understand how processing additives influence poly-SiC structure and electrical properties, the distribution of lattice defects and impurities across a specimen of hot-pressed 6H poly-SiC processed with p-type additives was visualized with high spatial resolution using a conductive atomic force microscopy approach in which a contact forming a nano-Schottky interface is scanned across the sample. The results reveal very intricate structures within poly-SiC, with each grain having a complex core-rim structure. This complexity results from the influence the additives have on the evolution of the microstructure during processing. It was found that the highest conductivities localized at rims as well as at the interface between the rim and the core. The conductivity of the cores is less than the conductivity of the rims due to a lower concentration of dopant. Analysis of the observed conductivities and current-voltage curves is presented in the context of nano-Schottky contact regimes where the conventional understanding of charge transport to diode operation is no longer valid.
Breakdown simulations in a focused microwave beam within the simplified model
Authors: Semenov V. E. , Rakova E. I. , Glyavin M. Yu. , Nusinovich G. S.
Published: July 2016

The simplified model is proposed to simulate numerically air breakdown in a focused microwave beam. The model is 1D from the mathematical point of view, but it takes into account the spatial non-uniformity of microwave field amplitude along the beam axis. The simulations are completed for different frequencies and different focal lengths of microwave beams. The results demonstrate complicated regimes of the breakdown evolution which represents a series of repeated ionization waves. These waves start at the focal point and propagate towards incident microwave radiation. The ionization wave parameters vary during propagation. At relatively low frequencies, the propagation regime of subsequent waves can also change qualitatively. Each next ionization wave is less pronounced than the previous one, and the breakdown evolution approaches the steady state with relatively small plasma density. The ionization wave parameters are sensitive to the weak source of external ionization, but the steady state is independent on such a source. As the beam focal length decreases, the stationary plasma density increases and the onset of the steady state occurs faster.
Leakage and field emission in side-gate graphene field effect transistors
Authors: Di Bartolomeo A. , Giubileo F. , Iemmo L. , Romeo F. , Russo S. , Unal S. , Passacantando M. , Grossi V. , Cucolo A. M.
Published: July 2016

We fabricate planar graphene field-effect transistors with self-aligned side-gate at 100 nm from the 500 nm wide graphene conductive channel, using a single lithographic step. We demonstrate side-gating below 1 V with conductance modulation of 35% and transconductance up to 0.5 mS/mm at 10 mV drain bias. We measure the planar leakage along the SiO2/vacuum gate dielectric over a wide voltage range, reporting rapidly growing current above 15 V. We unveil the microscopic mechanisms driving the leakage, as Frenkel-Poole transport through SiO2 up to the activation of Fowler-Nordheim tunneling in vacuum, which becomes dominant at higher voltages. We report a field-emission current density as high as 1 μA/μm between graphene flakes. These findings are important for the miniaturization of atomically thin devices.
Disilane as a growth rate catalyst of plasma deposited microcrystalline silicon thin films
Authors: Dimitrakellis P. , Kalampounias A. G. , Spiliopoulos N. , Amanatides E. , Mataras D. , Lahootun V. , Coeuret F. , Madec A.
Published: July 2016

The effect of small disilane addition on the gas phase properties of silane-hydrogen plasmas and the microcrystalline silicon thin films growth is presented. The investigation was conducted in the high pressure regime and for constant power dissipation in the discharge with the support of plasma diagnostics, thin film studies and calculations of discharge microscopic parameters and gas dissociation rates. The experimental data and the calculations show a strong effect of disilane on the electrical properties of the discharge in the pressure window from 2 to 3 Torr that is followed by significant raise of the electron number density and the drop of the sheaths electric field intensity. Deposition rate measurements show an important four to six times increase even for disilane mole fractions as low as 0.3 %. The deposition rate enhancement was followed by a drop of the material crystalline volume fraction but films with crystallinity above 40 % were deposited with different combinations of total gas pressure, disilane and silane molar ratios. The enhancement was partly explained by the increase of the electron impact dissociation rate of silane which rises by 40% even for 0.1% disilane mole fraction. The calculations of the gas usage, the dissociation and the deposition efficiencies show that the beneficial effect on the growth rate is not just the result of the increase of Si-containing molecules density but significant changes on the species participating to the deposition and the mechanism of the film growth are caused by the disilane addition. The enhanced participation of the highly sticking to the surface radical such as disilylene, which is the main product of disilane dissociation, was considered as the most probable reason for the significant raise of the deposition efficiency. The catalytic effect of such type of radical on the surface reactivity of species with lower sticking probability is further discussed, while it is also used to explain the restricted and sensitive process window where the disilane effect appears.
A novel broadband waterborne acoustic absorber
Authors: Wang Changxian , Wen Weibin , Huang Yixing , Chen Mingji , Lei Hongshuai , Fang Daining
Published: July 2016

In this paper, we extended the ray tracing theory in polar coordinate system, and originally proposed the Snell–Descartes law in polar coordinates. Based on these theories, a novel broadband waterborne acoustic absorber device was proposed. This device is designed with gradient-distributing materials along radius, which makes the incidence acoustic wave ray warps. The echo reduction effects of this device were investigated by finite element analysis, and the numerical results show that the reflectivity of acoustic wave for the new device is lower than that of homogenous and Alberich layers in almost all frequency 0-30 kHz at the same loss factor.
Assimilation of organic matter by two benthic consumers across gradients of latitude and nutrient enrichment
Authors: Nicastro Andrea , Lee Ka-Man , Bishop Melanie J.
Published: July 2016

In modifying the traits of producers, coastal development and latitude may influence the assimilation of organic matter resources by consumers. The aim of the present study was to assess spatial variation across gradients of latitude and diffuse nitrogen loading in: (1) the N content of the seagrass Zostera muelleri and the mangrove Avicennia marina; and (2) the ultimate organic matter sources (inferred from δ15N and δ13C signatures) of the detritivorous mud whelk Pyrazus ebeninus and the predatory polychaete Nephtys australiensis. It was hypothesised that the organic matter sources of each of the two consumers would vary spatially, following patterns of spatial variation in the N content of primary producers. Sampling in 12 estuaries of New South Wales, Australia, spanning 7° of latitude and variable nutrient loading revealed that the nitrogen content of Z. muelleri was negatively correlated with latitude and nitrogen loading, but the nitrogen content of A. marina leaves followed only latitude. Of the four organic matter sources considered by the present study, Z. muelleri was consistently the main source passed through the trophic chain to the detritivore P. ebeninus and the predator N. australiensis. Nevertheless, the proportionate contribution of Z. muelleri and microphytobenthos to the carbon sources of N. australiensis varied with latitude, the former negatively and the latter positively. These relationships suggest that latitude may influence carbon sources of consumers by modifying producer physicochemical traits.
Is the Kuroshio Current a strong barrier for the dispersal of the gizzard shad (Konosirus punctatus) in the East China Sea?
Authors: Song Na , Gao Tianxiang , Ying Yiping , Yanagimoto Takashi , Han Zhiqiang
Published: July 2016

The gizzard shad (Konosirus punctatus) is a common pelagic fish in the East China Sea. To evaluate the influence of Kuroshio Current in shaping the genetic structure of marine species, 10 populations of K. punctatus from Chinese and Japanese coastal waters were collected for analysis based on the mitochondrial DNA marker. All the Japanese populations exhibited higher nucleotide diversity than did Chinese populations. Two distinct clades were identified by the neighbour-joining tree based on haplotypes of Cyt b and the control region. Both AMOVA and pairwise Fst strongly supported the significant genetic divergence between Chinese and Japanese clades, which suggested strictly limited gene exchange. The mismatch distribution of Chinese clade and Japanese Clade B appeared to be unimodal, and Tajima’s D and Fu’s Fs statistics were significantly negative, and, therefore, the hypothesis of selective neutrality was rejected. The results indicated that the Kuroshio Current may not be the strong barrier for the dispersal of K. punctatus in the East China Sea. The climate of Pleistocene periods had played an important role in phylogeographical patterns of K. punctatus and the dispersal strategy of coastal species may be the major current physical barrier for the gene flow among populations from Chinese and Japanese coastal waters.
Effects of controlled traffic no-till system on soil chemical properties and crop yield in annual double-cropping area of the North China Plain
Authors: Lu Caiyun , Li Hongwen , He Jin , Wang Qingjie , Sarker Khokan Kumer , Li Wenying , Lu Zhanyuan , Rasaily Rabi G. , Li Hui , Chen Guangnan
Published: July 2016

A controlled traffic no-till system is a cropping system that has a significant potential to improve soil health, sustainability and crop yield. A pilot experiment was conducted to compare soil chemical properties and crop yields between controlled traffic no-till and random traffic in an annual double-cropping area of the North China Plain from 2005 to 2010. The experiment was performed using three treatments: (1) controlled traffic no-till (NTCT); (2) random traffic no-till (NTRT); and (3) conventional tillage (CT). The NTCT treatment significantly improved soil organic matter and total N compared with both NTRT and CT treatments and remarkably increased available P compared with CT treatment in the surface soil layer (0–10cm), but no significant differences were found in soil pH compared with both NTRT and CT treatments. However, in the 10–20- and 20–30-cm soil profiles, soil organic matter, total N and available P were reduced after NTCT treatment when compared with those obtained after CT treatment. At 0–10cm soil depths, soil bulk density under NTCT and NTRT was higher than in CT, whereas the opposite was true at soil depths of 10–30cm. Overall, it was found that the 6-year mean maize yield of NTCT and NTRT treatments was 10.9% and 1.1% higher respectively than the CT treatment, whereas the winter wheat yield was 1.1% and 3.0% higher respectively compared with the CT treatment. NTCT appears to be an improvement over current farming systems in an annual double-cropping area of the North China Plain.
Benchmarking nitrous oxide emissions in deciduous tree cropping systems
Authors: Swarts Nigel , Montagu Kelvin , Oliver Garth , Southam-Rogers Liam , Hardie Marcus , Corkrey Ross , Rogers Gordon , Close Dugald
Published: July 2016

Nitrous oxide (N2O) emissions contribute 6% of the global warming effect and are derived from the activity of soil-based microorganisms involved in nitrification and denitrification processes. There is a paucity of greenhouse gas emissions data for Australia’s horticulture industry. In this study we investigated N2O flux from two deciduous fruit tree crops, apples and cherries, in two predominant growing regions in eastern Australia, the Huon Valley in southern Tasmania (Lucaston – apples and Lower Longley – cherries), and high altitude northern New South Wales (Orange – apples and Young – cherries). Estimated from manual chamber measurements over a 12-month period, average daily emissions were very low ranging from 0.78gN2O-Nha–1day–1 in the apple orchard at Lucaston to 1.86gN2O-Nha–1day–1 in the cherry orchard in Lower Longley. Daily emissions were up to 50% higher in summer (maximum 5.27gN2O-Nha–1day–1 at Lower Longley) than winter (maximum 2.47gN2O-Nha–1day–1 at Young) across the four trial orchards. N2O emissions were ~40% greater in the inter-row than the tree line for each orchard. Daily flux rates were used as a loss estimate for annual emissions, which ranged from 298gN2O-Nha–1year–1 at Lucaston to 736gN2O-Nha–1year–1 at Lower Longley. Emissions were poorly correlated with soil temperature, volumetric water content, water filled porosity, gravimetric water content and matric potential – with inconsistent patterns between sites, within the tree line and inter-row and between seasons. Stepwise linear regression models for the Lucaston site accounted for less than 10% of the variance in N2O emissions, for which soil temperature was the strongest predictor. N2O emissions in deciduous tree crops were among the lowest recorded for Australian agriculture, most likely due to low rates of N fertiliser, cool temperate growing conditions and highly efficient drip irrigation systems. We recommend that optimising nutrient use efficiency with improved drainage and a reduction in soil compaction in the inter-row will facilitate further mitigation of N2O emissions.
Internal strain drives spontaneous periodic buckling in collagen and regulates remodeling
Authors: Dittmore Andrew , Silver Jonathan , Sarkar Susanta K. , Marmer Barry , Goldberg Gregory I. , Neuman Keir C.
Published: July 2016

Significance

Collagen fibrils resemble nanoscale cables that self-assemble and constitute the most prevalent protein structure in the body. Our experiments reveal unanticipated defects that form along collagen fibrils. These defects are the initiation sites of collagenase activity and represent a strain-sensitive mechanism for regulating tissue remodeling. The emergence of defects, their spatial periodicity, and fluctuations are quantitatively accounted for with a buckling model in which defects spontaneously form, repulsively interact, and self-heal.
Groundwater methane in relation to oil and gas development and shallow coal seams in the Denver-Julesburg Basin of Colorado
Authors: Sherwood Owen A. , Rogers Jessica D. , Lackey Greg , Burke Troy L. , Osborn Stephen G. , Ryan Joseph N.
Published: July 2016

Significance

The impact of unconventional oil and gas development on groundwater quality remains controversial. We use an archive of public domain data to examine factors influencing the distribution and sources of groundwater methane in the oil- and gas-producing Denver-Julesburg Basin of Colorado. Thermogenic stray gas sourced from deep oil and gas reservoirs impacted 42 water wells in 32 separate cases at a rate of about two cases per year from 2001 to 2014. The rate did not change after the introduction of horizontal drilling combined with high-volume hydraulic fracturing in 2010. The risk of stray gas contamination ranged from 0.12% of 35,000 water wells in the basin (lower estimate) to 4.5% of the 924 water wells that were tested (upper estimate).
Blind tests of RNA nearest-neighbor energy prediction
Authors: Chou Fang-Chieh , Kladwang Wipapat , Kappel Kalli , Das Rhiju
Published: July 2016

Significance

Understanding RNA machines and how their behavior can be modulated by chemical modification is increasingly recognized as an important biological and bioengineering problem, with continuing discoveries of riboswitches, mRNA regulons, CRISPR-guided editing complexes, and RNA enzymes. Computational strategies for understanding RNA energetics are being proposed, but have not yet faced rigorous tests. We describe a modeling strategy called RECCES–Rosetta (reweighting of energy-function collection with conformational ensemble sampling in Rosetta) that models the full ensemble of motions of RNA in single-stranded form and in helices, including nonstandard nucleotides, such as 2,6-diaminopurine, a variant of adenosine. When compared with experiments, including blind tests, the energetic accuracies of RECCES–Rosetta calculations are at levels close to experimental error, suggesting that computation can now be used to predict and design basic RNA energetics.
IL-17A–producing resident memory γδ T cells orchestrate the innate immune response to secondary oral
Listeria monocytogenes
infection
Authors: Romagnoli Pablo A. , Sheridan Brian S. , Pham Quynh-Mai , Lefrançois Leo , Khanna Kamal M.
Published: July 2016

Significance

Outbreaks of food-borne infections with
Listeria monocytogenes
can result in high mortality. Using a model of recombinant
L. monocytogenes
that models human infection in mice, we show that
L. monocytogenes
-specific memory γδ T cells in fact represent a resident memory (Trm) population in the mesenteric lymph node that secrete IL-17A and cluster with
L. monocytogenes
replication foci after secondary infection. Furthermore γδ Trms mediate the intranodal migration and redistribution of myeloid cells, which was necessary to contain the spread and growth of
L. monocytogenes
. Our findings demonstrate how γδ Trm cells orchestrate pathogen-induced innate immune responses. These observations provide the rationale for designing novel vaccination strategies to harness the ability of γδ Trm cells to provide protection against intestinal pathogens.
Equity and length of lifespan are not the same
Authors: Seligman Benjamin , Greenberg Gabi , Tuljapurkar Shripad
Published: July 2016

Significance

We find that the causes of death that have led to greater equality among lifespans are different from the causes that have led to longer average lifespan, also called life expectancy. Control of leading causes of death, such as heart disease, increased life expectancy, whereas medical interventions on infant mortality led to greater equality. Action to promote health equity will require further mitigation of the killers of young people rather than solely focusing on the most common causes of death.
Mitotic noncoding RNA processing promotes kinetochore and spindle assembly in Xenopus
Authors: Grenfell Andrew W. , Heald Rebecca , Strzelecka Magdalena
Published: July 2016

Transcription at the centromere of chromosomes plays an important role in kinetochore assembly in many eukaryotes, and noncoding RNAs contribute to activation of the mitotic kinase Aurora B. However, little is known about how mitotic RNA processing contributes to spindle assembly. We found that inhibition of transcription initiation or RNA splicing, but not translation, leads to spindle defects in Xenopus egg extracts. Spliceosome inhibition resulted in the accumulation of high molecular weight centromeric transcripts, concomitant with decreased recruitment of the centromere and kinetochore proteins CENP-A, CENP-C, and NDC80 to mitotic chromosomes. In addition, blocking transcript synthesis or processing during mitosis caused accumulation of MCAK, a microtubule depolymerase, on the spindle, indicating misregulation of Aurora B. These findings suggest that co-transcriptional recruitment of the RNA processing machinery to nascent mitotic transcripts is an important step in kinetochore and spindle assembly and challenge the idea that RNA processing is globally repressed during mitosis.
The loss of Ezh2 drives the pathogenesis of myelofibrosis and sensitizes tumor-initiating cells to bromodomain inhibition
Authors: Sashida Goro , Wang Changshan , Tomioka Takahisa , Oshima Motohiko , Aoyama Kazumasa , Kanai Akinori , Mochizuki-Kashio Makiko , Harada Hironori , Shimoda Kazuya , Iwama Atsushi
Published: July 2016

EZH2 is a component of polycomb repressive complex 2 (PRC2) and functions as an H3K27 methyltransferase. Loss-of-function mutations in EZH2 are associated with poorer outcomes in patients with myeloproliferative neoplasms (MPNs), particularly those with primary myelofibrosis (MF [PMF]). To determine how EZH2 insufficiency is involved in the pathogenesis of PMF, we generated mice compound for an Ezh2 conditional deletion and activating mutation in JAK2 (JAK2V617F) present in patients with PMF. The deletion of Ezh2 in JAK2V617F mice markedly promoted the development of MF, indicating a tumor suppressor function for EZH2 in PMF. The loss of Ezh2 in JAK2V617F hematopoietic cells caused significant reductions in H3K27 trimethylation (H3K27me3) levels, resulting in an epigenetic switch to H3K27 acetylation (H3K27ac). These epigenetic switches were closely associated with the activation of PRC2 target genes including Hmga2, an oncogene implicated in the pathogenesis of PMF. The treatment of JAK2V617F/Ezh2-null mice with a bromodomain inhibitor significantly attenuated H3K27ac levels at the promoter regions of PRC2 targets and down-regulated their expression, leading to the abrogation of MF-initiating cells. Therefore, an EZH2 insufficiency not only cooperated with active JAK2 to induce MF, but also conferred an oncogenic addiction to the H3K27ac modification in MF-initiating cells that was capable of being restored by bromodomain inhibition.
Early establishment of trees at the alpine treeline: idiosyncratic species responses to temperature-moisture interactions
Authors: Loranger Hannah , Zotz Gerhard , Bader Maaike Y.
Published: July 2016

On a global scale, temperature is the main determinant of arctic and alpine treeline position. However on a local scale, treeline form and position vary considerably due to other climatic factors, tree species ecology and life-stage-dependent responses. For treelines to advance poleward or uphill, the first steps are germination and seedling establishment. These earliest life stages may be major bottlenecks for treeline tree populations and will depend differently on climatic conditions than adult trees. We investigated the effect of soil temperature and moisture on germination and early seedling survival in a field experiment in the French Alps near the local treeline (2100 m a.s.l.) using passive temperature manipulations and two watering regimes. Five European treeline tree species were studied: Larix decidua , Picea abies , Pinus cembra , Pinus uncinata and Sorbus aucuparia . In addition, we monitored the germination response of three of these species to low temperatures under controlled conditions in growth chambers. The early establishment of these trees at the alpine treeline was limited either by temperature or by moisture, the sensitivity to one factor often depending on the intensity of the other. The results showed that the relative importance of the two factors and the direction of the effects are highly species-specific, while both factors tend to have consistent effects on both germination and early seedling survival within each species. We show that temperature and water availability are both important contributors to establishment patterns of treeline trees and hence to species-specific forms and positions of alpine treelines. The observed idiosyncratic species responses highlight the need for studies including several species and life-stages to create predictive power concerning future treeline dynamics.
Towards the knowledge-based design of universal influenza epitope ensemble vaccines
Authors: Sheikh Qamar M. , Gatherer Derek , Reche Pedro A , Flower Darren R.
Published: July 2016

Motivation: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes.

Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highly conserved and experimentally verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96 and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97 and 88% coverage of observed subtypes.

Availability and Implementation:  http://imed.med.ucm.es/Tools/episopt.html .

Contact:  d.r.flower@aston.ac.uk
SYNBADm: a tool for optimization-based automated design of synthetic gene circuits
Authors: Otero-Muras Irene , Henriques David , Banga Julio R.
Published: July 2016

Motivation: The design of de novo circuits with predefined performance specifications is a challenging problem in Synthetic Biology. Computational models and tools have proved to be crucial for a successful wet lab implementation. Natural gene circuits are complex, subject to evolutionary tradeoffs and playing multiple roles. However, most synthetic designs implemented to date are simple and perform a single task. As the field progresses, advanced computational tools are needed in order to handle greater levels of circuit complexity in a more flexible way and considering multiple design criteria.

Results: This works presents SYNBADm (SYNthetic Biology Automated optimal Design in Matlab), a software toolbox for the automatic optimal design of gene circuits with targeted functions from libraries of components. This tool makes use of global optimization to simultaneously search the space of structures and kinetic parameters. SYNBADm can efficiently handle high levels of circuit complexity and can consider multiple design criteria through multiobjective optimization. Further, it provides flexible design capabilities, i.e. the user can define the modeling framework, library of components and target performance function(s).

Availability and Implementation: SYNBADm runs under the popular MATLAB computational environment, and is available under GPLv3 license at https://sites.google.com/site/synbadm

Contact:  ireneotero@iim.csic.es or julio@iim.csic.es
PyPanda: a Python package for gene regulatory network reconstruction
Authors: van IJzendoorn David G.P. , Glass Kimberly , Quackenbush John , Kuijjer Marieke L.
Published: July 2016

Summary: PANDA ( P assing A ttributes between N etworks for D ata A ssimilation) is a gene regulatory network inference method that uses message-passing to integrate multiple sources of ‘omics data. PANDA was originally coded in C ++. In this application note we describe PyPanda, the Python version of PANDA. PyPanda runs considerably faster than the C ++ version and includes additional features for network analysis.

Availability and implementation: The open source PyPanda Python package is freely available at http://github.com/davidvi/pypanda .

Contact:  mkuijjer@jimmy.harvard.edu or d.g.p.van_ijzendoorn@lumc.nl
Childhood socioeconomic disadvantage is associated with lower mortality in older Japanese men: the JAGES cohort study
Authors: Tani Yukako , Kondo Naoki , Nagamine Yuiko , Shinozaki Tomohiro , Kondo Katsunori , Kawachi Ichiro , Fujiwara Takeo
Published: July 2016

Background: Childhood socioeconomic disadvantage has been previously linked to increased mortality risk in adulthood. However, most previous studies have focused on middle-aged adults in Western contexts. Here, we sought to examine the association between childhood socioeconomic status (SES) and mortality among healthy older Japanese adults.

Methods: We conducted a 3-year follow-up of participants in the Japan Gerontological Evaluation Study (JAGES), a population-based cohort of 65- to 103-year-old Japanese adults. Childhood SES was assessed by survey at baseline. Mortality from 2010 to 2013 was analysed for 15 449 respondents (7143 men and 8306 women). Cox regression models were used to estimate hazard ratios (HR) for risk of death.

Results: A total of 754 deaths occurred during the 3-year follow-up. Lower childhood SES was significantly associated with lower mortality in men, but not in women. Compared with men growing up in more advantaged childhood socioeconomic circumstances, the age-adjusted HR for men from low childhood SES backgrounds was 0.75 [95% confidence interval (CI): 0.56–1.00]. The association remained significant after adjustment for height, education, adult SES, municipalities of residence, health behaviours, disease status and current social relationships (HR = 0.64; 95% CI 0.47–0.87). This association was stronger among men aged 75 years or older, HR = 0.67 (95% CI: 0.47–0.95), compared with men aged 65–74 years, HR = 0.90 (95% CI: 0.54–1.51).

Conclusions: Childhood socioeconomic disadvantage is associated with lower mortality among men aged 75 years or older, which may be due to selective survival, or alternatively to childhood physical training or postwar calorie restriction in this generation of Japanese males.
Cancer-induced heterogeneous immunosuppressive tumor microenvironments and their personalized modulation
Authors: Yaguchi Tomonori , Kawakami Yutaka
Published: July 2016

Although recent cancer immunotherapy strategies, including immune-checkpoint blockade (i.e. blocking PD-1, PD-L1 or CTLA-4), have shown durable clinical effects in some (but not all) patients with various advanced cancers, further understanding of human immunopathology, particularly in tumor microenvironments, is essential to improve this type of therapy. The major hurdle for immunotherapy is the immunosuppression that is found in cancer patients. There are two types of immunosuppression: one is induced by gene alterations in cancer; the other is local adaptive immunosuppression, triggered by tumor-specific T cells in tumors. The former is caused by multiple mechanisms via various immunosuppressive molecules and via cells triggered by gene alterations, including activated oncogenes, in cancer cells. The various immunosuppressive mechanisms involve signaling cascades that vary among cancer types, subsets within cancer types and individual cancers. Therefore, personalized immune-interventions are necessary to appropriately target oncogene-induced signaling that modulates anti-cancer immune responses, on the basis of genetic and immunological analysis of each patient. Further understanding of human cancer immunopathology may lead to real improvement of current cancer immunotherapies.
Altering Speed of Locomotion
Authors: Van Den Bergh Bram , Heuvinck Nico , Schellekens Gaby A. C. , Vermeir Iris
Published: July 2016

Even though 80% of a shopper’s time in the store is spent moving from place to place, little is known about managing the pace of in-store traffic flow. Based on the store atmospherics literature, this article introduces interventions to optimize the pace of locomotion. A series of lab and field experiments demonstrates that changes in flooring affect customers’ walking speed. The number, the nature, and the relative salience of progress markers along a walking path toward a physical location communicate goal progress and thus the motivation to reach a particular destination. Consistent with a goal gradient account, customers walk faster when fewer progress markers are placed along the walking path to the goal. The effect of the number of progress markers diminishes when the markers are unrelated to the goal and reverses when the markers are relatively more salient than the goal. This article contributes to the goal literature by showing how markers affect perceptions of goal progress (i.e., level vs. rate of progress) and provides concrete insights to speed up and slow down customers’ walking speed in a retail environment.
The Systemic Risk Buffer for UK Banks: A Response to the Bank of England’s Consultation Paper
Authors: Vickers John
Published: July 2016

The article responds to the Bank of England’s (BoE) consultation paper of January 2016 on the systemic risk buffer for UK ring-fenced banks. It argues that, contrary to its proposed policy, the BoE should apply the highest permitted buffer rate—3 per cent of risk-weighted assets of common equity—to all large ring-fenced banks. The BoE’s reasons for lowering its estimate of optimal equity capital requirements are assessed critically.
Input Specificity and the Propagation of Idiosyncratic Shocks in Production Networks
*
Authors: Barrot Jean-Noël , Sauvagnat Julien
Published: July 2016

This article examines whether firm-level idiosyncratic shocks propagate in production networks. We identify idiosyncratic shocks with the occurrence of natural disasters. We find that affected suppliers impose substantial output losses on their customers, especially when they produce specific inputs. These output losses translate into significant market value losses, and they spill over to other suppliers. Our point estimates are economically large, suggesting that input specificity is an important determinant of the propagation of idiosyncratic shocks in the economy.
Earthquakes, Religion, and Transition to Self-Government in Italian Cities*
Authors: Belloc Marianna , Drago Francesco , Galbiati Roberto
Published: July 2016

This article presents a unique historical experiment to explore the dynamics of institutional change in the Middle Ages. We have assembled a novel data set, where information on political institutions for northern central Italian cities between 1000 and 1300 is matched with detailed information on the earthquakes that occurred in the area and period of interest. Exploiting the panel structure of the data, we document that the occurrence of an earthquake retarded institutional transition from autocratic regimes to self-government (the commune) in cities where the political and the religious leaders were the same person (episcopal see cities), but not in cities where political and religious powers were distinct (non–episcopal see cities). Such differential effect holds for destructive seismic episodes and for events that were felt by the population but did not cause any material damage to persons or objects. Ancillary results show that seismic events provoked a positive and statistically significant differential effect on the construction and further ornamentation of religious buildings between episcopal and non–episcopal see cities. Our findings are consistent with the idea that earthquakes, interpreted in the Middle Ages as manifestation of the will and outrage of God, represented a shock to people’s religious beliefs and, as a consequence, enhanced the ability of political-religious leaders to restore social order after a crisis relative to the emerging communal institutions. This interpretation is supported by historical evidence.
The Liquidity Premium of Near-Money Assets*
Authors: Nagel Stefan
Published: July 2016

This article examines the link between the opportunity cost of money and time-varying liquidity premia of near-money assets. Higher interest rates imply higher opportunity costs of holding money and hence a higher premium for the liquidity service benefits of assets that are close substitutes for money. Consistent with this theory, short-term interest rates in the United States, United Kingdom, and Canada have a strong positive relationship with the liquidity premium of Treasury bills and other near-money assets over periods going back to the 1920s. Once the opportunity cost of money is taken into account, Treasury security supply variables lose their explanatory power for the liquidity premium, except for transitory short-run effects. These findings indicate a high elasticity of substitution between money and near-money assets. As a consequence, a central bank that follows an interest rate operating target not only elastically accommodates and neutralizes shocks to money demand, but effectively also shocks to near-money asset supply and demand.
Fatigue effect of elastocaloric properties in natural rubber
Authors: Sebald Gael , Xie Zhongjian , Guyomar Daniel
Published: July 2016

In the framework of elastocaloric (eC) refrigeration, the fatigue effect on the eC effect of natural rubber (NR) is investigated. Repetitive deformation cycles at engineering strain regime from 1 to 6 results in a rapid rupture (approx. 800 cycles). Degradation of properties and fatigue life are then investigated at three different strain regimes with the same strain amplitude: before onset strain of strain-induced crystallization (SIC) (strain regime of 0–3), onset strain of melting (strain regime of 2–5) and high strain of SIC (strain regime of 4–7). Strain of 0–3 leads to a low eC effect and cracking after 2000 cycles. Strain of 2–5 and 4–7 results in an excellent crack growth resistance and much higher eC effect with adiabatic temperature changes of 3.5 K and 4.2 K, respectively, thanks to the effect of SIC. The eC stress coefficient index
γ
(ratio between eC temperature change and applied stress) for strains of 2–5 and 4–7 are
γ
2–5
=4.4 K MPa
−1
and
γ
4–7
=1.6 K MPa
−1
, respectively, demonstrating the advantage of the strain regime 2–5. Finally, a high-cycle test up to 1.7×10
5
cycles is successfully applied to the NR sample with very little degradation of eC properties, constituting an important step towards cooling applications.

This article is part of the themed issue ‘Taking the temperature of phase transitions in cool materials’.