bluuebunny/crossref_metadata_2025 huggingface dataset:
THE IMPACT OF NEW DRUG LAUNCHES ON LIFE-YEARS LOST IN 2015 FROM 19 TYPES OF CANCER IN 36 COUNTRIES
Authors: Lichtenberg Frank R.
Published: August 2018

This study employs a two-way fixed effects research design to measure the mortality impact and cost-effectiveness of cancer drugs: It analyzes the correlation across 36 countries between the relative mortality from 19 types of cancer in 2015 and the relative number of drugs previously launched in that country to treat that type of cancer, controlling for relative incidence. The sample size (both in terms of number of observations and population covered) of this study is considerably larger than the sample sizes of previous studies; a new and improved method of analyzing the lag structure of the relationship between drug launches and life-years lost is used; and a larger set of measures of the burden of cancer is analyzed. The number of DALYs and life-years lost are unrelated to drug launches 0–4 years earlier. This is not surprising, since utilization of a drug tends to be quite low during the first few post-launch years. Moreover, there is likely to be a lag of several years between utilization of a drug and its impact on mortality. However, mortality is significantly inversely related to the number of drug launches at least 5 years earlier, especially to drug launches 5–9 years earlier. One additional drug for a cancer site launched during 2006–2010 is estimated to have reduced the number of 2015 DALYs due to cancer at that site by 5.8%;; one additional drug launched during 1982–2005 is estimated to have reduced the number of 2015 DALYs by about 2.6%. Lower quality (or effectiveness) of earlier vintage drugs may account for their smaller estimated effect. We estimate that drugs launched during the entire 1982–2010 period reduced the number of cancer DALYs in 2015 by about 23.0%, and that, in the absence of new drug launches during 1982–2010, there would have been 26.3 million additional DALYs in 2015. Also, the nine countries with the largest number of drug launches during 1982–2010 are estimated to have had 14% fewer cancer DALYs (controlling for incidence) in 2015 than the nine countries with the smallest number of drug launches during 1982–2010. Estimates of the cost per life-year gained in 2015 from drugs launched during 2006–2010 range between $1,635 (life-years gained at all ages) and $2,820 (life-years gained before age 65). These estimates are similar to those obtained in previous country-specific studies of Belgium, Canada, and Mexico, and are well below the estimate obtained in one study of Switzerland. Mortality in 2015 is strongly inversely related to the number of drug launches in 2006–2010. If the relationship between mortality in 2020 and the number of drug launches in 2011–2015 is similar, drug launches 5–9 years earlier will reduce mortality even more (by 9.9%) between 2015 and 2020 than they did (by 8.4%) between 2010 and 2015.
AN ANALYSIS OF FEMALE LABOR SUPPLY, HOME PRODUCTION, AND HOUSEHOLD CONSUMPTION EXPENDITURES
Authors: Forrester Kellie , Klein Jennifer
Published: August 2018

The United States saw a rapid transformation of its labor market when the female employment to population ratio nearly doubled from 1950 to 2000. As women shift their hours from the home sector to the market sector, goods that were previously produced in the home may be replaced by market services. This paper uses the Panel Study for Income Dynamics, Consumer Expenditure Survey, and the American Time Use Survey to analyze the extent to which households replace home production with purchased market services, and how the relationship between men’s and women’s labor supplies affects these decisions. We show that women who are employed spend less time on home production activities that have close market alternatives than women who are not employed. Additionally, expenditures on market services that can replace home production are higher for married households in which the woman is employed compared to those with nonworking women.
Special Collections: What Are They and How Do We Build Them?
Authors: King Vanessa
Published: August 2018

This article provides a very brief introduction to practical information useful for building special collections at an academic law library rather than addressing theory or the history of special collections.
Don't Burn the Books, Read Them!
Authors: Watson Amanda
Published: August 2018

Why do we still have books? To answer this question with views based not on the market trend, nor on the popular feeling that print is outdated and irrelevant, but on the American Bar Association's stated mission of Law Libraries to provide resources that enable legal education,1 this article reviews the potential benefits and determents of different types of legal sources using both print and online formats and discusses whether external pressures should outweigh these factors dependent on the audience.
SOME APPLICATIONS OF SUPERCOMPACT EXTENDER BASED FORCINGS TO HOD
Authors: GITIK MOTI , MERIMOVICH CARMI
Published: August 2018

Supercompact extender based forcings are used to construct models with HOD cardinal structure different from those of V. In particular, a model where all regular uncountable cardinals are measurable in HOD is constructed.
ABSTRACT ω-LIMIT SETS
Authors: BRIAN WILL
Published: August 2018

The shift map σ on ω* is the continuous self-map of ω* induced by the function n ↦ n + 1 on ω. Given a compact Hausdorff space X and a continuous function f : X → X, we say that (X, f) is a quotient of (ω*, σ) whenever there is a continuous surjection Q : ω*→ X such that Q ○ σ = σ ○ f.

Our main theorem states that if the weight of X is at most ℵ1, then (X, f) is a quotient of (ω*, σ), if and only if f is weakly incompressible (which means that no nontrivial open U ⊆ X has $f\left( {\bar{U}} \right) \subseteq U$). Under CH, this gives a complete characterization of the quotients of (ω*, σ) and implies, for example, that (ω*, σ−1) is a quotient of (ω*, σ).

In the language of topological dynamics, our theorem states that a dynamical system of weight ℵ1 is an abstract ω-limit set if and only if it is weakly incompressible.

We complement these results by proving (1) our main theorem remains true when ℵ1 is replaced by any κ < p, (2) consistently, the theorem becomes false if we replace ℵ1 by ℵ2, and (3) OCA + MA implies that (ω*, σ−1) is not a quotient of (ω*, σ).
ON THE SET-THEORETIC STRENGTH OF ELLIS’ THEOREM AND THE EXISTENCE OF FREE IDEMPOTENT ULTRAFILTERS ON ω
Authors: TACHTSIS ELEFTHERIOS
Published: August 2018

Ellis’ Theorem (i.e., “every compact Hausdorff right topological semigroup has an idempotent element”) is known to be proved only under the assumption of the full Axiom of Choice (AC); AC is used in the proof in the disguise of Zorn’s Lemma.

In this article, we prove that in ZF, Ellis’ Theorem follows from the Boolean Prime Ideal Theorem (BPI), and hence is strictly weaker than AC in ZF. In fact, we establish that BPI implies the formally stronger (than Ellis’ Theorem) statement “for every family ${\cal A} = \{ ({S_i},{ \cdot _i},{{\cal T}_i}):i \in I\}$ of nontrivial compact Hausdorff right topological semigroups, there exists a function f with domain I such that $f\left( i \right)$ is an idempotent of ${S_i}$, for all $i \in I$”, which in turn implies ACfin (i.e., AC for sets of nonempty finite sets).

Furthermore, we prove that in ZFA, the Axiom of Multiple Choice (MC) implies Ellis’ Theorem for abelian semigroups (i.e., “every compact Hausdorff right topological abelian semigroup has an idempotent element”) and that the strictly weaker than MC (in ZFA) principle LW (i.e., “every linearly ordered set can be well-ordered”) implies Ellis’ Theorem for linearly orderable semigroups (i.e., “every compact Hausdorff right topological linearly orderable semigroup has an idempotent element”); thus the latter formally weaker versions of Ellis’ Theorem are strictly weaker than BPI in ZFA. Yet, it is shown that no choice is required in order to prove Ellis’ Theorem for well-orderable semigroups.

We also show that each one of the (strictly weaker than AC) statements “the Tychonoff product $2^{\Cal R} $ is compact and Loeb” and $BPI_{\Cal R}$ (BPI for filters on ${\Cal R}$) implies “there exists a free idempotent ultrafilter on ω” (which in turn is not provable in ZF). Moreover, we prove that the latter statement does not imply $BP{I_\omega }$ (BPI for filters on ω) in ZF, hence it does not imply any of $AC_{\Cal R} $ (AC for sets of nonempty sets of reals) and $BPI_{\Cal R} $ in ZF, either.

In addition, we prove that the statements “there exists a free ultrafilter on ω”, “there exists a free ultrafilter on ω which is not idempotent”, and “for every IP set $A \subseteq \omega$, there exists a free ultrafilter ${\cal F}$ on ω such that $A \in {\cal F}$” are pairwise equivalent in ZF.
ON VANISHING CRITERIA THAT CONTROL FINITE GROUP STRUCTURE II
Authors: BROUGH JULIAN , KONG QINGJUN
Published: August 2018

The first author [J. Brough, ‘On vanishing criteria that control finite group structure’, J. Algebra458 (2016), 207–215] has shown that for certain arithmetical results on conjugacy class sizes it is enough to consider only the vanishing conjugacy class sizes. In this paper we further weaken the conditions to consider only vanishing elements of prime power order.
MINIMAL EXCEPTIONAL -GROUPS
Authors: CHAMBERLAIN ROBERT
Published: August 2018

For a finite group $G$, denote by $\unicode[STIX]{x1D707}(G)$ the degree of a minimal permutation representation of $G$. We call $G$ exceptional if there is a normal subgroup $N\unlhd G$ with $\unicode[STIX]{x1D707}(G/N)>\unicode[STIX]{x1D707}(G)$. To complete the work of Easdown and Praeger [‘On minimal
faithful permutation representations of finite groups’, Bull. Aust.
Math. Soc.38(2) (1988), 207–220], for all primes $p\geq 3$, we describe an exceptional group of order $p^{5}$ and prove that no exceptional group of order $p^{4}$ exists.
A NOTE ON GUNNINGHAM’S FORMULA
Authors: LEE JUNHO
Published: August 2018

Gunningham [‘Spin Hurwitz numbers and topological quantum field theory’,
Geom. Topol.20(4) (2016), 1859–1907]
constructed an extended topological quantum field theory (TQFT) to obtain a
closed formula for all spin Hurwitz numbers. In this note, we use a gluing
theorem for spin Hurwitz numbers to re-prove Gunningham’s formula. We also
describe a TQFT formalism naturally induced by the gluing theorem.
The Land–Labour Hypothesis in a Settler Economy: Wealth, Labour and Household Composition on the South African Frontier
Authors: Cilliers Jeanne , Green Erik
Published: August 2018

Traditional frontier literature identifies a positive correlation between land availability and fertility. A common explanation is that the demand for child labour is higher in newly established frontier regions compared to older, more densely populated farming regions. In this paper, we contribute to the debate by analysing the relationship between household composition and land availability in a closing frontier region, i.e. the Graaff-Reinet district in South Africa’s Cape Colony from 1798–1828. We show that the number of children in farming households increased with frontier closure, while the presence of non-family labourers decreased over time. Contrasting with the classic interpretation, we explain this by acknowledging that the demand for family labour was not a function of its marginal productivity and that farmers reacted differently to diminishing land availability depending on their wealth. Poorer households, which made up the majority of this frontier population, responded to shrinking land availability by employing relatively more family labour, while the wealthiest group invested in strengthening market access.

TRANSLATED ABSTRACTS FRENCH – GERMAN – SPANISH

Jeanne Cilliers et Erik Green.L’hypothèse sur la disponibilité de terres et la main d’œuvre dans une économie de colons: richesse, main d’œuvre et composition du ménage à la frontière sud-africaine.

La littérature traditionnelle de la frontière identifie une corrélation positive entre la disponibilité de terres et la fertilité. Une explication courante est que la demande de travail des enfants est supérieure dans les régions frontalières nouvellement établies, par comparaison avec d’anciennes régions agricoles plus densément peuplées. Dans cet article, nous contribuons au débat en analysant la relation entre la composition du ménage et la disponibilité de terres dans une région frontalière en train de fermer, le district de Graaff-Reinert dans la Colonie du Cap en Afrique du Sud, entre 1798 et 1828. Les auteurs montrent que le nombre des enfants dans les ménages agricoles augmenta avec la fermeture des frontières, tandis que la présence d’ouvriers agricoles non familiaux déclina au fil des ans. Contrairement à l’interprétation classique, nous expliquons ce phénomène en reconnaissant que la demande de travailleurs familiaux ne dépendit pas de sa productivité marginale, et que les exploitants agricoles réagirent différemment selon leur richesse à la disponibilité de terres diminuante. Les foyers plus pauvres, qui constituaient la majorité de cette population frontalière, répondirent à la disponibilité de terres déclinante en employant relativement plus de main d’œuvre familiale, tandis que le groupe le plus riche investit dans le renforcement de l’accès au marché.

Traduction:Christine Plard
Of Trees, a Son, and Kingship: Recovering an Ancient Chinese Dream
Authors: Shaughnessy Edward L.
Published: August 2018

The first volume of the Tsinghua University Warring States bamboo-strip manuscripts contains a text with passages that match medieval quotations of a text referred to asCheng Wu 程寤orAwakening at Cheng, which in turn is said to be a lost chapter of theYi Zhou Shu 逸周書orLeftover Zhou Documents. The passages concern one of Chinese literature's earliest interpretations of a dream, and were quoted in medieval encyclopedias in their sections on dreams. This article discusses the significance of this discovery both for Chinese textual history and for the interpretation of this particular dream. In particular, it shows that trees seen in the dream predict the Zhou conquest of Shang, and the subsequent Shang acquiescence to Zhou rule. It also notes that this discovery simultaneously confirms the antiquity of this text, but also calls into question the dominant traditional interpretation of the dream.
Doing the Contemporary: Pina Bausch as a Conceptual Artist
Authors: Siegmund Gerald
Published: August 2018

This essay asks the question whether and in what respect the work of German choreographer Pina Bausch can be considered to be contemporary. Building on Peter Osborne's definition of the contemporary as “a disjunctive unity of present times,” I aim to extract the conceptual concerns of Bausch's work that thus far have received little critical attention. In so doing, I first consider the temporal relations articulated in Bausch's work, particularly her relation to the past that comes to define the present, exposing its claims to unity as a fiction. Second, I focus on the medial aspects of Bausch's work, including her 1988/89 film, The Plaint of the Empress. By making the media aspect of Bausch's work the center of my attention, I argue that it is precisely the work's media saturation that allows for its contemporary distribution, display, and formatting. It is here that Bausch's contemporaneity as a principle of work and a working principle can be found.
Jay Pather Reimagining Site-Specific Cartographies of Belonging
Authors: Katrak Ketu H.
Published: August 2018

This essay examines Jay Pather's site-specific work Cityscapes (2002) within a theoretical discussion of the conjuncture and disjuncture of space and race in South Africa. Jay Pather, a South African of Indian ancestry, an innovative choreographer and curator of site-specific works, creatively uses space to inspire social change by providing access and challenging exclusions—social, cultural, political—of black and colored South Africans during apartheid (1948–1994) and after. A progressive vision underlies his avant-garde work expressed via a hybrid choreographic palette of South African classical and popular dance styles, Indian classical dance, modern and contemporary dance. His choreography is performed across South Africa and the African continent as well as in Denmark, Mumbai, and New York City.
How to Re-View Things with Words? Dance Criticism as Translation—Pina Bausch
Authors: Thurner Christina
Published: August 2018

Critics described Pina Bausch's work as “absolutely contemporary” and as being “important dance heritage,” which is precisely the opposite of contemporary, namely, historical. This contradictoriness—though productive in its own right—is symptomatic of the perspective of dance journalism brought to bear on Pina Bausch's later works in particular. But even reviews of her earlier works are a far cry from perceiving the artist in a consistent manner, some even going so far as to criticize her for being “outdated.” Apparently, Bausch's art continuously poses a challenge for dance critics because it defies easy categorization in aesthetic terms, thereby undermining the implicit postulates and classificatory criteria underlying dance reviews. There is—at least in the German-speaking area—broad consensus regarding the functions of today's dance reviews as a text genre: as a translation of dance into language, dance reviews describe, analyze, and judge. With a focus on reviews of pieces by Pina Bausch, this essay proposes to investigate how dance is translated (“trans-posed”) by considering the questions: what do reviews do when they put things into words? How are their own seemingly firm categorizations and postulates thereby destabilized or at least opened to debate?
THE JANUS-FACED NATURE OF DEBT: RESULTS FROM A DATA-DRIVEN COINTEGRATED SVAR APPROACH
Authors: Guerini Mattia , Moneta Alessio , Napoletano Mauro , Roventini Andrea
Published: August 2018

In this paper, we investigate the causal effects of public and private debts on US output dynamics. We estimate a battery of Cointegrated Structural Vector Autoregressive models, and we identify structural shocks by employing Independent Component Analysis, a data-driven technique which avoids ad-hoc identification choices. The econometric results suggest that the impact of debt on economic activity isJanus-faced. Public debt shocks have positive and persistent influence on economic activity. In contrast, rising private debt has a milder positive impact on gross domestic product, but it fades out over time. The analysis of the possible transmission mechanisms reveals that public debtcrowds inprivate consumption and investment. In contrast, mortgage debt fuels consumption and output in the short-run, but shrinks them in the medium-run.
Two case studies from a virtual reality intervention for delusions: feasibility and preliminary evidence
Authors: Dietrichkeit Mona , Flint Kristina , Krieger Eva , Grzella Karsten , Nagel Matthias , Moritz Steffen
Published: August 2018

The use of virtual reality (VR) interventions for psychosis is on the rise. As information-processing biases such as overconfidence in memory are likely to be involved in the formation and maintenance of delusions, VR could also be used to correct cognitive distortions and in turn ameliorate delusions. The present study illustrates two case studies in which a VR intervention was employed to reduce delusions by means of correcting experiences. Participants navigated four virtual environments via a head-mounted display (HMD) and computer and were asked to recollect previously seen faces and objects and to rate their response confidence. The scenarios were created to elicit false memories. Immediately after each response, they received feedback to correct possible overconfidence in false memories. We present two case studies to illustrate individual differences. Both participants benefited from the intervention: delusions were reduced from pre- to post-assessment (after 3 weeks) as measured with the Positive and Negative Syndrome Scale and Psychotic Symptom Scale. This was corroborated by results on the Paranoia Checklist and the Community Assessment of Psychic Experiences collected immediately after the session. Immediate effects also showed a reduction in delusion conviction rate. The present study provides preliminary evidence that delusions may be ameliorated by a VR paradigm designed to correct memory overconfidence. Cybersickness emerged as a problem in one of the patients.
New Techniques and Data for Understanding the Global Soil Respiration Flux
Authors: Bond‐Lamberty Ben
Published: August 2018

Soil respiration (Rs; the soil surface‐to‐atmosphere CO2 flux) has been measured in the field for decades, but only recently have we begun to assemble and leverage these small‐scale but extensive data. Recently, Zhao et al. (2017, https://doi.org/10.1002/2016ef000480) applied a novel artificial neural network model to the problem of estimating the global Rs flux and understanding its variations between regions and biomes. Their results point to a convergence in estimates of global Rs, and the power of leveraging the long record of observed Rs in global ecosystems, but also to uncertainties about soils' response to climate change. It will take a combination of long‐term studies, data syntheses, modeling intercomparisons, and probably a new generation of sampling networks and experiments to fully resolve these questions.
Stability and Reactions of CaCO3 Polymorphs in the Earth's Deep Mantle
Authors: Zhang Zhigang , Mao Zhu , Liu Xi , Zhang Yigang , Brodholt John
Published: August 2018

As an important component of carbonates in the mantle, CaCO3 is a major carrier of carbon from the surface to the deep interiors. In recent years, new varieties of CaCO3 polymorphs have been continuously predicted by first principles simulations and verified by experiments. The findings of these polymorphs open the possibility of stabilizing CaCO3 component in the lowermost mantle. Here, through extensive first principles simulations, we inspect the stability and reactions of high‐pressure CaCO3 polymorphs at high temperatures. Systematic errors from approximations to the exchange‐correlation functional in density functional theory have been essentially eliminated with a generalized rescaling method to increase the predictability of the simulations. We find temperature has important effects on the stabilities and the reactions of CaCO3 polymorphs with mantle minerals. In particular, the tetrahedrally structured CaCO3‐polymorph (space group P21/c) is found to be sensitive to temperature with a positive Clapeyron slope of 15.81(6) MPa/K. Reacting with MgSiO3, CaCO3 is shown to be less stable than MgCO3 over the whole mantle pressures (to ~136 GPa) above ~1500 K. And CaCO3 is demonstrated to readily react with SiO2 even in the cold subduction slabs. Thus, high temperature greatly increases the tendency of partitioning calcium into the silicates, and CaCO3 is not likely to be the major host of carbon in the Earth's deep mantle.
Lateral Mixing Processes in the Hadean
Authors: O'Neill C. J. , Zhang S.
Published: August 2018

Samples of ancient Eoarchean volcanism suggest the existence of isotopically distinct mantle domains. 142Nd evidence suggests that these domains formed within the first several hundred million years of Earth's history and were preserved until circa 3.7 Ga—a span of almost 800 Myr. Here we explore evolving mantle convection models under Hadean conditions to constrain mantle mixing dynamics and in particular focus on the generation, or preservation, of upper mantle hemispheric compositional anomalies. We find that initially radially homogenous models fail to produce hemispheric anomalies spontaneously due to mixing processes and that rheological and buoyancy effects, or asymmetric processes such as plate tectonics or meteorite impacts, do not generate long‐lived heterogeneities in upper mantle composition from homogenous initial conditions. In contrast, models initiated with compositional variations can preserve these hemispheric differences of periods >800 Myr despite vigorous internal convection, as a function of the proclivity of these models to exhibit stagnant‐lid behavior, resulting in isolated convection cells with restricted lateral transport.
Sensitivity of Seismic Noise Correlation Functions to Global Noise Sources
Authors: Sager Korbinian , Boehm Christian , Ermert Laura , Krischer Lion , Fichtner Andreas
Published: August 2018

Surface waves in seismic noise correlation functions are routinely exploited for tomographic studies. However, the observation and proper interpretation of body waves is considerably more difficult. To understand body wave generation in particular and the emergence of noise correlation signals in general, we investigate the sensitivity of correlation functions with respect to global noise sources. Treating noise correlation functions as self‐consistent observables, without the enforcement of Green function retrieval, enables us to investigate the quantitative contribution of different noise sources in space to a signal in a specific time window. The source sensitivity kernel for a surface wave reveals the expected dominant and broad region of stationary phase and thereby confirms the robustness of noise tomography in its current state. In contrast, kernels for potential body waves are highly oscillatory and indicate significant contributions from cross terms, for example, from body wave‐surface wave interactions. While the short‐wavelength nature of the body wave kernel may in the future allow us to infer noise sources with great detail, the importance of cross terms combined with the natural heterogeneity of noise sources renders an interpretation of such an arrival as a pure body wave almost impossible. Furthermore, we show that even long‐wavelength Earth structure significantly distorts sensitivity kernels. It is therefore essential to incorporate 3‐D heterogeneities into high‐resolution imaging of ambient noise sources, especially at higher frequencies.
Circulating insulin-like growth factor I modulates mood and is a biomarker of vulnerability to stress: from mouse to man
Authors: Santi A. , Bot M. , Aleman A. , Penninx B. W. J. H. , Aleman I. Torres
Published: August 2018

Individual susceptibility to anxiety disorders after maladaptive responses to stress is not well understood. We now report that while exploring stress responses in mice after traumatic brain injury (TBI), a condition associated to stress susceptibility, we observed that the anxiogenic effects of either TBI or exposure to life-threatening experiences (predator) were blocked when both stressors were combined. Because TBI increases the entrance into the brain of serum insulin-like growth factor I (IGF-I), a known modulator of anxiety with a wide range of concentrations in the human population, we then determined whether circulating IGF-I is related to anxiety measures. In mice, anxiety-like responses to predator were inversely related to circulating IGF-I levels. Other indicators of mood regulation such as sensitivity to dexamethasone suppression and expression levels of blood and brain FK506 binding protein 5 (FKBP5), a co-chaperone of the glucocorticoid receptor that regulates its activity, were also associated to circulating IGF-I. Indeed, brain FKBP5 expression in mice was stimulated by IGF-I. In addition, we observed in a large human cohort (n = 2686) a significant relationship between plasma IGF-I and exposure to recent stressful life events, while FKBP5 expression in blood cells was significantly associated to plasma IGF-I levels. Collectively, these data indicate that circulating IGF-I appears to be involved in mood homeostasis across different species. Furthermore, the data in mice allow us to indicate that IGF-I may be acting at least in part by modulating FKBP5 expression.
Endogenous transcripts control miRNA levels and activity in mammalian cells by target-directed miRNA degradation
Authors: Ghini Francesco , Rubolino Carmela , Climent Montserrat , Simeone Ines , Marzi Matteo J. , Nicassio Francesco
Published: August 2018

Little is known about miRNA decay. A target-directed miRNA degradation mechanism (TDMD) has been suggested, but further investigation on endogenous targets is necessary. Here, we identify hundreds of targets eligible for TDMD and show that an endogenous RNA (Serpine1) controls the degradation of two miRNAs (miR-30b-5p and miR-30c-5p) in mouse fibroblasts. In our study, TDMD occurs when the target is expressed at relatively low levels, similar in range to those of its miRNAs (100–200 copies per cell), and becomes more effective at high target:miRNA ratios (>10:1). We employ CRISPR/Cas9 to delete the miR-30 responsive element within Serpine1 3'UTR and interfere with TDMD. TDMD suppression increases miR-30b/c levels and boosts their activity towards other targets, modulating gene expression and cellular phenotypes (i.e., cell cycle re-entry and apoptosis). In conclusion, a sophisticated regulatory layer of miRNA and gene expression mediated by specific endogenous targets exists in mammalian cells.
Structural basis of cell wall anchoring by SLH domains in Paenibacillus alvei
Authors: Blackler Ryan J. , López-Guzmán Arturo , Hager Fiona F. , Janesch Bettina , Martinz Gudrun , Gagnon Susannah M. L. , Haji-Ghassemi Omid , Kosma Paul , Messner Paul , Schäffer Christina , Evans Stephen V.
Published: August 2018

Self-assembling protein surface (S-) layers are common cell envelope structures of prokaryotes and have critical roles from structural maintenance to virulence. S-layers of Gram-positive bacteria are often attached through the interaction of S-layer homology (SLH) domain trimers with peptidoglycan-linked secondary cell wall polymers (SCWPs). Here we present an in-depth characterization of this interaction, with co-crystal structures of the three consecutive SLH domains from the Paenibacillus alvei S-layer protein SpaA with defined SCWP ligands. The most highly conserved SLH domain residue SLH-Gly29 is shown to enable a peptide backbone flip essential for SCWP binding in both biophysical and cellular experiments. Furthermore, we find that a significant domain movement mediates binding by two different sites in the SLH domain trimer, which may allow anchoring readjustment to relieve S-layer strain caused by cell growth and division.
A highly reactive precursor in the iron sulfide system
Authors: Matamoros-Veloza Adriana , Cespedes Oscar , Johnson Benjamin R. G. , Stawski Tomasz M. , Terranova Umberto , de Leeuw Nora H. , Benning Liane G.
Published: August 2018

Iron sulfur (Fe–S) phases have been implicated in the emergence of life on early Earth due to their catalytic role in the synthesis of prebiotic molecules. Similarly, Fe–S phases are currently of high interest in the development of green catalysts and energy storage. Here we report the synthesis and structure of a nanoparticulate phase (FeSnano) that is a necessary solid-phase precursor to the conventionally assumed initial precipitate in the iron sulfide system, mackinawite. The structure of FeSnano contains tetrahedral iron, which is compensated by monosulfide and polysulfide sulfur species. These together dramatically affect the stability and enhance the reactivity of FeSnano.
Ultra-narrow-band near-infrared thermal exciton radiation in intrinsic one-dimensional semiconductors
Authors: Nishihara Taishi , Takakura Akira , Miyauchi Yuhei , Itami Kenichiro
Published: August 2018

Thermal radiation is the most primitive light emission phenomenon of materials. Broadband radiation from red-hot materials is well known as the kick-starter phenomenon of modern quantum physics in the early twentieth century; even nowadays, its artificial control plays a central role in modern science and technology. Herein, we report the fundamental thermal radiation properties of intrinsic one-dimensional semiconductors and metals, which have not been elucidated because of significant technical challenges. We observed narrow-band near-infrared radiation from semiconducting single-walled carbon nanotubes at 1000–2000 K in contrast to its broadband metallic counterpart. We confirm that the ultra-narrow-band radiation is enabled by the thermal generation of excitons that are hydrogen-like neutral exotic atoms comprising mutually bound electrons and holes. Our findings uncover the robust quantum correlations in intrinsic one-dimensional semiconductors even at 2000 K; additionally, the findings provide an opportunity for excitonic optothermal engineering toward the realization of efficient thermophotovoltaic energy harvesting.
Author Correction: P53 and mTOR signalling determine fitness selection through cell competition during early mouse embryonic development
Authors: Bowling Sarah , Di Gregorio Aida , Sancho Margarida , Pozzi Sara , Aarts Marieke , Signore Massimo , Schneider Michael D. , Martinez-Barbera Juan Pedro , Gil Jesús , Rodríguez Tristan A.
Published: August 2018

The original version of this article contained an error in the spelling of Juan Pedro Martinez-Barbera, which was incorrectly given as Juan Pedro Martinez Barbera. This error has now been corrected in both the PDF and HTML versions of the Article.
Neural correlates of video game empathy training in adolescents: a randomized trial
Authors: Kral Tammi R. A. , Stodola Diane E. , Birn Rasmus M. , Mumford Jeanette A. , Solis Enrique , Flook Lisa , Patsenko Elena G. , Anderson Craig G. , Steinkuehler Constance , Davidson Richard J.
Published: August 2018

The ability to understand emotional experiences of others, empathy, is a valuable skill for effective social interactions. Various types of training increase empathy in adolescents, but their impact on brain circuits underlying empathy has not been examined. Video games provide a unique medium familiar and engaging to adolescents and can be used to deliver training at scale. We developed an empathy training video game, Crystals of Kaydor (Crystals), and investigated whether playing Crystals increases empathic accuracy (EA) and related brain activation in adolescents (N = 74; 27 female; mean age(sd) = 12.8(0.7) years; age range 11–14 years). Participants completed a resting state functional MRI (rs-fMRI) scan and an EA task during an fMRI scan before and after 2 weeks of daily gameplay with either the empathy training game, Crystals (N = 34), or the commercial video game Bastion (N = 40), an active control condition. There were no group differences in EA improvement following gameplay, however, engagement with training aspects of Crystals was associated with a higher increase in EA-related activation in right temporoparietal junction following gameplay. Moreover, rs-fMRI connectivity in empathy-related brain circuits (posterior cingulate–medial prefrontal cortex; MPFC) was stronger after Crystals gameplay compared to Bastion. The more individuals’ EA increased following Crystals versus Bastion, the stronger their rs-fMRI connectivity in brain circuits relevant for emotion regulation (amygdala-MPFC). These findings suggest that a video game designed to increase empathic accuracy produces behaviorally-relevant, functional neural changes in fewer than 6 h of gameplay in adolescents.
Downstream Products are Potent Inhibitors of the Heparan Sulfate 2-O-Sulfotransferase
Authors: Thieker David F. , Xu Yongmei , Chapla Digantkumar , Nora Chelsea , Qiu Hong , Felix Thomas , Wang Lianchun , Moremen Kelley W. , Liu Jian , Esko Jeffrey D. , Woods Robert J.
Published: August 2018

Heparan Sulfate (HS) is a cell signaling molecule linked to pathological processes ranging from cancer to viral entry, yet fundamental aspects of its biosynthesis remain incompletely understood. Here, the binding preferences of the uronyl 2-O-sulfotransferase (HS2ST) are examined with variably-sulfated hexasaccharides. Surprisingly, heavily sulfated oligosaccharides formed by later-acting sulfotransferases bind more tightly to HS2ST than those corresponding to its natural substrate or product. Inhibition assays also indicate that the IC50 values correlate simply with degree of oligosaccharide sulfation. Structural analysis predicts a mode of inhibition in which 6-O-sulfate groups located on glucosamine residues present in highly-sulfated oligosaccharides occupy the canonical binding site of the nucleotide cofactor. The unexpected finding that oligosaccharides associated with later stages in HS biosynthesis inhibit HS2ST indicates that the enzyme must be separated temporally and/or spatially from downstream products during biosynthesis in vivo, and highlights a challenge for the enzymatic synthesis of lengthy HS chains in vitro.
The influence of latitude, geographic distance, and habitat discontinuities on genetic variation in a high latitude montane species
Authors: Hindley J. A. , Graham B. A. , Pulgarin-R. P. C. , Burg T. M.
Published: August 2018

Examining the factors that influence contemporary genetic patterns is important given the alarming rate at which natural environments are changing. In particular habitat fragmentation and climate change are expected to influence the distribution and diversity of natural populations. In this study we used both mitochondrial control region (mtDNA) and microsatellite data to answer the following questions about genetic diversity and divergence in mountain chickadees (Poecile gambeli) a resident bird species in western North America: (1) Do populations exhibit similar levels of genetic diversity across the range? (2) What is the genetic affinity of western populations in Oregon and Washington? (3) Do genetic patterns exhibit isolation by distance, or are genetic patterns more heavily influenced by habitat discontinuity? We tested the effects of isolation by distance and habitat distribution on genetic structure by analyzing 266 samples from 17 sites across western Canada and the United States. We found a near significant relationship between genetic diversity and latitude, however, our results indicate that overall, latitude is not a strong predictor of genetic diversity. Our analyses of populations in Oregon and Washington revealed a mismatch between patterns detected with mtDNA and microsatellite data. In particular, Washington clustered with the Coast Range/Cascades/Rocky Mountain mtDNA group, but with populations in southern Oregon/California based on microsatellite data. These results suggest the presence of a contact zone in Washington between the two mtDNA clades Coast Range/Cascades/Rocky Mountain and southern Oregon/California clades. Finally, our study revealed a greater effect of isolation by distance than isolation by habitat for both mtDNA and microsatellite data. Overall the isolation by distance signal was greater for mtDNA than microsatellite patterns. The greater signal of isolation by distance on mtDNA patterns likely reflects the strong effects of Pleistocene glaciations in shaping genetic patterns in western North America.
Integrative analysis of the inter-tumoral heterogeneity of triple-negative breast cancer
Authors: Chiu Alec M. , Mitra Mithun , Boymoushakian Lari , Coller Hilary A.
Published: August 2018

Triple-negative breast cancers (TNBC) lack estrogen and progesterone receptors and HER2 amplification, and are resistant to therapies that target these receptors. Tumors from TNBC patients are heterogeneous based on genetic variations, tumor histology, and clinical outcomes. We used high throughput genomic data for TNBC patients (n = 137) from TCGA to characterize inter-tumor heterogeneity. Similarity network fusion (SNF)-based integrative clustering combining gene expression, miRNA expression, and copy number variation, revealed three distinct patient clusters. Integrating multiple types of data resulted in more distinct clusters than analyses with a single datatype. Whereas most TNBCs are classified by PAM50 as basal subtype, one of the clusters was enriched in the non-basal PAM50 subtypes, exhibited more aggressive clinical features and had a distinctive signature of oncogenic mutations, miRNAs and expressed genes. Our analyses provide a new classification scheme for TNBC based on multiple omics datasets and provide insight into molecular features that underlie TNBC heterogeneity.
Expressed protein profile of a Tectomicrobium and other microbial symbionts in the marine sponge Aplysina aerophoba as evidenced by metaproteomics
Authors: Chaib De Mares Maryam , Jiménez Diego Javier , Palladino Giorgia , Gutleben Johanna , Lebrun Laura A. , Muller Emilie E. L. , Wilmes Paul , Sipkema Detmer , van Elsas Jan Dirk
Published: August 2018

Aplysina aerophoba is an emerging model marine sponge, with a well-characterized microbial community in terms of diversity and structure. However, little is known about the expressed functional capabilities of its associated microbes. Here, we present the first metaproteomics-based study of the microbiome of A. aerophoba. We found that transport and degradation of halogenated and chloroaromatic compounds are common active processes in the sponge microbiomes. Our data further reveal that the highest number of proteins were affiliated to a sponge-associated Tectomicrobium, presumably from the family Entotheonellaceae, as well as to the well-known symbiont “Candidatus Synechococcus spongiarium”, suggesting a high metabolic activity of these two microorganisms in situ. Evidence for nitric oxide (NO) conversion to nitrous oxide was consistently observed for Tectomicrobia across replicates, by production of the NorQ protein. Moreover, we found a potential energy-yielding pathway through CO oxidation by putative Chloroflexi bacteria. Finally, we observed expression of enzymes that may be involved in the transformation of chitin, glycoproteins, glycolipids and glucans into smaller molecules, consistent with glycosyl hydrolases predicted from analyses of the genomes of Poribacteria sponge symbionts. Thus, this study provides crucial links between expressed proteins and specific members of the A. aerophoba microbiome.
Author Correction: Composition and Use of Cannabis Extracts for Childhood Epilepsy in the Australian Community
Authors: Suraev A. , Lintzeris N. , Stuart J. , Kevin R. C. , Blackburn R. , Richards E. , Arnold J. C. , Ireland C. , Todd L. , Allsop D. J. , McGregor I. S.
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Seasonal variability of water characteristics in the Challenger Deep observed by four cruises
Authors: Huang Caijing , Xie Qiang , Wang Dongxiao , Shu Yeqiang , Xu Hongzhou , Xiao Jingen , Zu Tingting , Long Tong , Zhang Tiecheng
Published: August 2018

Thirty conductivity-temperature-depth profiler casts in the Challenger Deep were conducted during four cruises from December 2015 to February 2017. Two cruises took place in the summer, and two in the winter. The results demonstrated that water characteristics varied seasonally. The temperature minimum values were the same between the four cruises, but its depth was noticeably shallower in the winter than that in the summer. The θ-S diagram indicated that deep water is more saline in the summer than that in winter at the same potential temperature. Mixing is more intense between 5000 and 6800 m in the summer than that in the winter. The dissipation rate and eddy diffusivity vertically averaged between 5000 and 6800 m in the summer were εT = 3.277 × 10−8m2s−3 and KzT = 2.58 × 10−2m2s−1, respectively. The geostrophic flows below the reference level of 3000 dbar were cyclonic in the summer, travelling westwards in the northern and eastwards in the southern areas of the Challenger Deep.
Flexible Localized Surface Plasmon Resonance Sensor with Metal–Insulator–Metal Nanodisks on PDMS Substrate
Authors: Chang Chiao-Yun , Lin Hsiang-Ting , Lai Ming-Sheng , Shieh Teng-Yi , Peng Chien-Chung , Shih Min-Hsiung , Tung Yi-Chung
Published: August 2018

The small sized, flexible, high-performed and bio-compatible sensing devices are the critical elements to realize the bio-related detection or on-site health monitoring systems. In this work, the flexible localized surface plasmon resonance (LSPR) bio-sensors were demonstrated by integrating the metal–insulator–metal (MIM) nanodisks with bio-compatible polydimethylsiloxane (PDMS) substrate. The different geometries of MIM nanodisk sensors were investigated and optimized to enhance the spatial overlap of the LSPR waves with the environment, which lead to a high sensitivity of 1500 nm/RIU. The omni-directional characteristics of LSPR resonances were beneficial for maintaining the device sensitivity stable under various bending curvatures. Furthermore, the flexible MIM nanodisk LSPR sensor was applied to detect A549 cancer cells in PBS+ solution. The absorption peak of the MIM-disk LSPR sensor obviously redshift to easily distinguish between the phosphate buffered saline (PBS+) solution with A549 cancer cells and without cells. Therefore, the flexible MIM nanodisk LSPR sensor is suitable to develop on-chip microfluidic biosensors for detection of cancer cells on nonplanar surfaces.
Scalable Gastric Resident Systems for Veterinary Application
Authors: Hayward Alison , Bensel Taylor , Mazdiyasni Hormoz , Rogner Jaimie , Kirtane Ameya R. , Lee Young-Ah Lucy , Hua Tiffany , Bajpayee Ambika , Collins Joy , McDonnell Shane , Cleveland Cody , Lopes Aaron , Wahane Aniket , Langer Robert , Traverso Giovanni
Published: August 2018

Gastric resident dosage forms have been used successfully in farm animals for the delivery of a variety of drugs helping address the challenge of extended dosing. Despite these advances, there remains a significant challenge across the range of species with large variation in body size. To address this, we investigate a scalable gastric resident platform capable of prolonged retention. We investigate prototypes in dimensions consistent with administration and retention in the stomachs of two species (rabbit and pig). We investigate sustained gastric retention of our scalable dosage form platform, and in pigs show the capacity to modulate drug release kinetics of a model drug in veterinary practice, meloxicam, with our dosage form. The ability to achieve gastric residence and thereby enable sustained drug levels across different species may have a significant impact in the welfare of animals in both research, agricultural, zoological, and clinical practice settings.
Highly Stable Persistent Photoconductivity with Suspended Graphene Nanoribbons
Authors: Suzuki Hiroo , Ogura Noritada , Kaneko Toshiro , Kato Toshiaki
Published: August 2018

Graphene nanoribbon (GNR), also known as 1-dimensional graphene, with a non-zero band gap has a huge potential for various electrical and optoelectrical applications because of its high transparency, flexibility, controllable band gap, and unique edge states. Recent advances in the synthesis of GNR enable us to show the possibility of GNRs as future high performance electrical devices. However, the applicability of GNRs to optoelectrical devices is unclear. Here we report that suspended GNR devices can show persistent photoconductivity (PPC) with long decay time (over 72 h) and adequate environmental stability. Repeated non-volatile memory operation is also demonstrated with an integrated PPC device using GNRs. This very stable PPC device can be applied to a wide variety of fields such as ultra-low-power non-volatile memory, nanoscale imaging, and biological sensors. Our results have opened the door to advance the study of GNRs in novel directions such as optoelectrical applications.