bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of mid‐level clouds over West Africa
Authors: Bourgeois Elsa , Bouniol Dominique , Couvreux Fleur , Guichard Françoise , Marsham John H. , Garcia‐Carreras Luis , Birch Cathryn E. , Parker Douglas J.
Published: November 2017

Mid‐level clouds, located between 2 and 9 km height, are ubiquitous in the tropical belt. However, few studies have documented their characteristics and tried to identify the associated thermodynamic properties, particularly in West Africa. This region is characterized by a strong seasonality with precipitation occurring in the Sahel from June to September (monsoon season). This period also coincides with the annual maximum of the cloud cover. Here, we document the macro‐ and microphysical properties of mid‐level clouds, the environment in which such clouds occur, as well as their radiative properties across West Africa. To do so, we combined high‐resolution observations from two ground‐based sites (including lidar and cloud radar) in contrasted environments: one in the Sahel (Niamey, AMMA campaign, 2006) and the other in the Sahara (Bordj Badji Mokhtar, Fennec campaign, June 2011) along with the merged CloudSat‐CALIPSO satellite products. The results show that mid‐level clouds are found throughout the year with a predominance around the monsoon season early in the morning. They also are preferentially observed in the southern and western parts of West Africa. They are usually thin (most of them are less than 1000 m deep) and as observed in Niamey, mainly composed of liquid water. A clustering method applied to Niamey data allows us to distinguish three different types of cloud: one with low bases, one with high bases and another with large thicknesses. The two first cloud families are capped by an inversion. The last family is associated with a large vertical moisture transport and likely has the highest radiative effect at the Earth's surface among the three cloud types.
Data‐driven learning and planning for environmental sampling
Authors: Ma Kai‐Chieh , Liu Lantao , Heidarsson Hordur K. , Sukhatme Gaurav S.
Published: November 2017

Robots such as autonomous underwater vehicles (AUVs) and autonomous surface vehicles (ASVs) have been used for sensing and monitoring aquatic environments such as oceans and lakes. Environmental sampling is a challenging task because the environmental attributes to be observed can vary both spatially and temporally, and the target environment is usually a large and continuous domain whereas the sampling data are typically sparse and limited. The challenges require that the sampling method must be informative and efficient enough to catch up with the environmental dynamics. In this paper, we present a planning and learning method that enables a sampling robot to perform persistent monitoring tasks by learning and refining a dynamic “data map” that models a spatiotemporal environment attribute such as ocean salinity content. Our environmental sampling framework consists of two components: To maximize the information collected, we propose an informative planning component that efficiently generates sampling waypoints that contain the maximal information; to alleviate the computational bottleneck caused by large‐scale data accumulated, we develop a component based on a sparse Gaussian process whose hyperparameters are learned online by taking advantage of only a subset of data that provides the greatest contribution. We validate our method with both simulations running on real ocean data and field trials with an ASV in a lake environment. Our experiments show that the proposed framework is both accurate in learning the environmental data map and efficient in catching up with the dynamic environmental changes.
Black Phosphorus Quantum Dots with Renal Clearance Property for Efficient Photodynamic Therapy
Authors: Guo Tao , Wu Ying , Lin Yan , Xu Xin , Lian Hao , Huang Guoming , Liu Ji‐Zan , Wu Xiaoping , Yang Huang‐Hao
Published: November 2017

Black phosphorus (BP) nanomaterials have emerged as rapidly rising stars in the field of nanomedicine. In this work, BP quantum dots (BPQDs) are synthesized and their potential as photosensitizers is investigated for the first time. The BPQDs present good stability in physiological medium and no appreciable cytotoxicity. More importantly, the BPQDs can be rapidly eliminated from the body in their intact form via renal clearance due to their ultrasmall hydrodynamic diameter (5.4 nm). Both in vitro and in vivo studies indicate that the BPQDs have excellent photodynamic effect under light irradiation that can effectively generate reactive oxygen species to kill cancer cells. The BPQDs thus can serve as biocompatible and powerful photosensitizers for efficient photodynamic therapy.
Magnetically Responsive Elastomer–Silicon Hybrid Surfaces for Fluid and Light Manipulation
Authors: Yang Zining , Park Jun Kyu , Kim Seok
Published: November 2017

Stimuli‐responsive surfaces with tunable fluidic and optical properties utilizing switchable surface topography are of significant interest for both scientific and engineering research. This work presents a surface involving silicon scales on a magnetically responsive elastomer micropillar array, which enables fluid and light manipulation. To integrate microfabricated silicon scales with ferromagnetic elastomer micropillars, transfer printing‐based deterministic assembly is adopted. The functional properties of the surface are completely dictated by the scales with optimized lithographic patterns while the micropillar array is magnetically actuated with large‐range, instantaneous, and reversible deformation. Multiple functions, such as tunable wetting, droplet manipulation, tunable optical transmission, and structural coloration, are designed, characterized, and analyzed by incorporating a wide range of scales (e.g., bare silicon, black silicon, photonic crystal scales) in both in‐plane and out‐of‐plane configurations.
Recent progress on fabrication and drug delivery applications of nanostructured hydroxyapatite
Authors: Mondal Sudip , Dorozhkin Sergy V. , Pal Umapada
Published: November 2017

Through this brief review, we provide a comprehensive historical background of the development of nanostructured hydroxyapatite (nHAp), and its application potentials for controlled drug delivery, drug conjugation, and other biomedical treatments. Aspects associated with efficient utilization of hydroxyapatite (HAp) nanostructures such as their synthesis, interaction with drug molecules, and other concerns, which need to be resolved before they could be used as a potential drug carrier in body system, are discussed. This review focuses on the evolution of perceptions, practices, and accomplishments in providing improved delivery systems for drugs until date. The pioneering developments that have presaged today's fascinating state of the art drug delivery systems based on HAp and HAp‐based composite nanostructures are also discussed. Special emphasis has been given to describe the application and effectiveness of modified HAp as drug carrier agent for different diseases such as bone‐related disorders, carriers for antibiotics, anti‐inflammatory, carcinogenic drugs, medical imaging, and protein delivery agents. As only a very few published works made comprehensive evaluation of HAp nanostructures for drug delivery applications, we try to cover the three major areas: concepts, practices and achievements, and applications, which have been consolidated and patented for their practical usage. The review covers a broad spectrum of nHAp and HAp modified inorganic drug carriers, emphasizing some of their specific aspects those needed to be considered for future drug delivery applications.

This article is categorized under:

Implantable Materials and Surgical Technologies > Nanomaterials and Implants

Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease

Nanotechnology Approaches to Biology > Cells at the Nanoscale
Investigating the Effect of Copper(II) Coordination Compound with Azodicarbonamide Ligand on the Phase‐Stabilization of Ammonium Nitrate
Authors: Asgari Abdoalreza , Ghani Kamal , Keshavarz Mohammad Hossein
Published: November 2017

A novel copper(II) coordination compound was synthesized using azodicarbonamide (ADC) as ligand (CuII‐ADC). The structural, morphological, and optical properties of the synthesized material are investigated using X‐ray diffraction, field emission scanning electron microscopy, Fourier transform infrared, and diffuse reflectance spectroscopy. Evaluation of the obtained results indicates that ADC coordinated to copper ions. Ammonium nitrate (AN) is an affordable oxidant, which is widely used in gas generators. Since AN shows crystal structure transformation in ambience temperature accompanied by a change in volume, its application is limited without phase stabilization. For phase stabilization of AN, AN/CuII‐ADC composite is prepared and its phase transitions is studied using differential scanning calorimetry. The results indicate that ANIV↔ANIII phase transition can be eliminated by hydrogen bonding between AN and CuII‐ADC.
The Price of Uncertainty in Present-Biased Planning
Authors: Albers Susanne , Kraft Dennis
Published: November 2017

The tendency to overestimate immediate utility is a common cognitive bias. As a result people behave inconsistently over time and fail to reach long-term goals. Behavioral economics tries to help affected individuals by implementing external incentives. However, designing robust incentives is often difficult due to imperfect knowledge of the parameter $$\beta \in (0,1]$$

β
∈
(
0
,
1
]

quantifying a person’s present bias. Using the graphical model of Kleinberg and Oren [8], we approach this problem from an algorithmic perspective. Based on the assumption that the only information about $$\beta $$
β
is its membership in some set $$B \subset (0,1]$$

B
⊂
(
0
,
1
]

, we distinguish between two models of uncertainty: one in which $$\beta $$
β
is fixed and one in which it varies over time. As our main result we show that the conceptual loss of efficiency incurred by incentives in the form of penalty fees is at most 2 in the former and $$1 + \max B/\min B$$

1
+
max
B
/
min
B

in the latter model. We also give asymptotically matching lower bounds and approximation algorithms.
Eigenstate thermalization in the Sachdev-Ye-Kitaev model
Authors: Sonner Julian , Vielma Manuel
Published: November 2017

Abstract

The eigenstate thermalization hypothesis (ETH) explains how closed unitary quantum systems can exhibit thermal behavior in pure states. In this work we examine a recently proposed microscopic model of a black hole in AdS2, the so-called Sachdev-Ye-Kitaev (SYK) model. We show that this model satisfies the eigenstate thermalization hypothesis by solving the system in exact diagonalization. Using these results we also study the behavior, in eigenstates, of various measures of thermalization and scrambling of information. We establish that two-point functions in finite-energy eigenstates approximate closely their thermal counterparts and that information is scrambled in individual eigenstates. We study both the eigenstates of a single random realization of the model, as well as the model obtained after averaging of the random disordered couplings. We use our results to comment on the implications for thermal states of a putative dual theory, i.e. the AdS2 black hole.
A swamp of non-SUSY vacua
Authors: Danielsson U. H. , Dibitetto G. , Vargas S. C.
Published: November 2017

Abstract

We consider known examples of non-supersymmetric AdS7 and AdS4 solutions arising from compactifications of massive type IIA supergravity and study their stability, taking into account the coupling between closed- and open-string sector excitations. Generically, open strings are found to develop modes with masses below the Breitenlohner-Freedman (BF) bound. We comment on the relation with the Weak Gravity Conjecture, and how this analysis may play an important role in examining the validity of non-supersymmetric constructions in string theory.
2D gravitational Mabuchi action on Riemann surfaces with boundaries
Authors: Bilal Adel , de Lacroix Corinne
Published: November 2017

Abstract

We study the gravitational action induced by coupling two-dimensional non-conformal, massive matter to gravity on a Riemann surface with boundaries. A small-mass expansion gives back the Liouville action in the massless limit, while the first-order mass correction allows us to identify what should be the appropriate generalization of the Mabuchi action on a Riemann surface with boundaries. We provide a detailed study for the example of the cylinder. Contrary to the case of manifolds without boundary, we find that the gravitational Lagrangian explicitly depends on the space-point, via the geodesic distances to the boundaries, as well as on the modular parameter of the cylinder, through an elliptic θ-function.
A clearer vision of composite coatings
Authors: Bailey Nick
Published: November 2017

How one of the strongest, lightest automotive construction materials is overcoming the problems that have so far kept it from entering the mainstream.
A revolution in low-cost carbon fiber production
Authors: Church David
Published: November 2017

LeMond Composites’ patent pending manufacturing process will produce low-cost, high performance carbon fiber for a range of industries, from transportation to renewable energy.
RADIOCARBON DATING OF TECHNOLOGICAL TRANSITIONS: THE LATE HOLOCENE SHIFT FROM ATLATL TO BOW IN NORTHWESTERN SUBARCTIC CANADA
Authors: Grund Brigid Sky , Huzurbazar Snehalata V.
Published: November 2017

Precolumbian archaeologists traditionally focus on periods of stability rather than change when constructing regional cultural chronologies. However, the advent of large databases of radiocarbon dates and the proliferation of open-source software environments such as R now allow archaeologists to understand technological transitions with greater chronological precision than has been historically possible. In this study, we employ Monte Carlo procedures, Bayes’ Theorem, the R package Bchron, and IntCal13 to address three chronological topics. We calculate the minimum number of dates required on atlatl and bow technologies to robustly date this late Holocene transition in Subarctic northwestern Canada, analyze previously published dates on organic projectile diagnostics to determine whether bows and atlatls overlapped for an observable amount of time, and estimate the years of calendric time that they overlapped. Results indicate that minimum sample sizes of 29 atlatl and 19 bow dates are required to characterize this particular transition in our study area. Actual radiocarbon dates show that bow and atlatl technologies temporally co-occurred within this region for 174 ± 135 (1σ) actual calendar years. Quantitative analyses such as these open the door to testing hypotheses that explain why and how technological transitions occur within and between (pre)historic groups.
The Ethics of Affective Leadership: Organizing Good Encounters Without Leaders
Authors: Munro Iain , Thanem Torkild
Published: November 2017

This article addresses the fundamental question of what is ethical leadership by rearticulating relations between leaders and followers in terms of “affective leadership.” The article develops a Spinozian conception of ethics which is underpinned by a deep suspicion of ethical systems that hold obedience as a primary virtue. We argue that the existing research into ethical leadership tends to underplay the ethical capacities of followers by presuming that they are in need of direction or care by morally superior leaders. In contrast, affective leadership advocates a profoundly political version of ethics, which involves people in the pursuit of joyful encounters that augment our capacity to affect and be affected by others. Instead of being led by people in leadership positions, we are led by active affections that enhance our capacity for moral action.
Law Reporting in England 1550–1650
Authors: Baker John
Published: November 2017

English law reports between 1550 and 1650 seem far more accessible today than the “year books” that preceded them. This is not because they were produced differently, for a different readership or by a different kind of reporter, but because the legal system itself had changed. We also encounter in the Tudor period the first reports written by eminent lawyers, two of whom (Plowden and Coke) saw a selection of them through the press in their lifetimes. Recent editorial work on the better reports has revealed something of the way they were compiled, and also of what was omitted when contemporary notes were turned into printed volumes.

Coke's reports are the most famous, traditionally cited simply as The Reports. Work has just begun on an edition of the underlying notebooks (first discovered just forty years ago), which will probably require at least six volumes. Coke's reporting style was controversial, and his alleged subjectivity was seized upon by Francis Bacon as one of the grounds for bringing him down in 1616. However, Bacon's scheme of 1617 to engage professional reporters, paid by the crown, seems to have collapsed after a few years. Law reporting was thus to remain a matter of private initiative until the end of the eighteenth century, and many of the best reports – even those written by judges – have still not been published. Anyone seeking to trace the evolution of a legal doctrine or practice before about 1700 must regard manuscript reports as an essential recourse.
The (South) American Dream: Mobility and Economic Outcomes of First- and Second-Generation Immigrants in Nineteenth-Century Argentina
Authors: Pérez Santiago
Published: November 2017

I study the mobility and economic outcomes of European immigrants and their children in nineteenth-century Argentina, the second largest destination country during the Age of Mass Migration. I use new data linking males across censuses and passenger lists of arrivals to Buenos Aires. First-generation immigrants experienced faster occupational upgrading than natives. Occupational mobility was substantial relative to Europe; immigrants holding unskilled occupations upon arrival experienced high rates of occupational upgrading. Second-generation immigrants outperformed the sons of natives in terms of literacy, occupational status and access to property, and experienced higher rates of intergenerational mobility out of unskilled occupations.
What is the importance of islands to environmental conservation?
Authors: KUEFFER CHRISTOPH , KINNEY KEALOHANUIOPUNA
Published: November 2017

This article discusses four features of islands that make them places of special importance to environmental conservation. First, investment in island conservation is both urgent and cost-effective. Islands are threatened hotspots of diversity that concentrate unique cultural, biological and geophysical values, and they form the basis of the livelihoods of millions of islanders. Second, islands are paradigmatic places of human–environment relationships. Island livelihoods have a long tradition of existing within spatial, ecological and ultimately social boundaries and are still often highly dependent on local resources and social cohesion. Island cultures and their rich biocultural knowledge can be an important basis for revitalizing and innovating sustainable human–nature relationships. Third, islands form a global web that interlinks biogeographic regions and cultural spaces. They are nodes in a global cultural network: as multicultural island societies, through diaspora islander communities on continents and through numerous political and trade relationships among islands and between islands and countries on continents. Fourth, islands can serve as real-world laboratories that enable scientific innovation, integration of local and generalized knowledge and social learning and empowerment of local actors. We conclude that island systems can serve as globally distributed hubs of innovation, if the voices of islanders are better recognized.
Class matters: the sociolinguistics ofgooseandgoatin Manchester English
Authors: Baranowski Maciej
Published: November 2017

This paper reports on patterns of sociolinguistic variation and change in Manchester'sgooseandgoatvowels on the basis of the acoustic analysis of 122 speakers, stratified by age, gender, socioeconomic status, and ethnicity.Goosefronting is an internal change showing little social differentiation, except before /l/ as inschoolandpool, where, in contrast to most other dialects of English,gooseshows advanced fronting inversely correlated with socioeconomic status.Goatfronting, on the other hand, is a change brought from outside the dialect by the highest status groups, displaying a pattern of monotonic social stratification, a female lead, and a strong effect of ethnicity. The role of attitudes toward the community in the realization of the vowels is compared with the effect of social class construed in terms of distances between social groups. Social class turns out to be a better predictor, suggesting that the role of attitudes and identity may be overestimated in research eschewing a systematic exploration of social class at the same time.
Space–Emotion in Acousmatic Music
Authors: Ratti Federico Schumacher , Bravo Claudio Fuentes
Published: November 2017

This article presents a multimodal exploratory study aimed at searching for evidence that can guide us in the adoption and/or improvement of appropriate theoretical–methodological approaches for studying the role of the spatiality/spatialisation of sound and the cognitive/affective empathic processes involved in the acousmatic experience. For this purpose, controlled listening sessions were conducted in which fragments of different loudspeaker music were presented. The subjects reported their emotional experience and the degree of familiarity they assigned to each sound fragment. Specific questions for the acousmatic fragments inquire into the potential relationships between the sound stimulus and the emotion declared by the subjects. From these experiences, qualitative reports were obtained through a semi-structured interview, and electrodermal activity (EDA) logs were recorded in parallel for an intended group. Based on these results, it is argued that spatiality might be linked to a complex cognitive–affective response from the listeners and emerges as a distinctive element of the meaning that the listeners ascribe to their acousmatic musical experience.
Sound as Multiplicity: Listening with Thoreau, Cage and Serres
Authors: Byrne Ben
Published: November 2017

Despite the gradual proliferation of scholarly work around sound, and in particular its role in experimental music, there is little explicitly sonic philosophy that attempts to provide a ground for such research. Decades after the work of Pierre Schaeffer to theorise theobjet sonore– sound object – and John Cage’s (1973: 10) call to ‘let sounds be themselves’, there remain few ontological and epistemological frameworks to support investigations into aesthetic, ethical and political questions related to experimental music practice and the place of sound in it. This makes writing about sound difficult and contributes to a lack of clarity or specificity in the use of terms such as ‘sound’, ‘noise’ and ‘silence’. In this article I seek to address this, connecting the work of transcendentalist Henry David Thoreau, experimental music composer and thinker Cage and philosopher Michel Serres with my own experience to develop an account of sound in experimental music that approaches it as multiplicity. This allows sound to be heard as physical, perceptual and conceptual and brings into question the reproducibility of sound, emphasising the place of sound as part of its environment.
Studying Sonorous Objects to Develop Frameworks for Improvisation
Authors: Mcauliffe Sam
Published: November 2017

French musique concrète artist Pierre Schaeffer pioneered new ways of listening to and studying sound. His study and manipulation of recorded sounds to create music changed the way contemporary musicians, from a multitude of disciplines, approach making music. Additionally, Schaeffer’s treatise on acousmatic listening to sonorous objects has deeply influenced contemporary sound studies. In this article, I elucidate how musique concrète has informed my practice-led research project,Looking Awry– from which I will discuss two case studies. I outline how acousmatic listening to field recordings from everyday environments informed the development of performance strategies that guide improvised musical performance; a malleable practice that can be applied to a variety of performance settings.
Rebuilding Bridges: Toward a Feminist Research Agenda for Postwar Reconstruction
Authors: Bergeron Suzanne , Cohn Carol , Duncanson Claire
Published: November 2017

As feminists who think about war and peacebuilding, we cannot help but encounter the complex, entwined political economic processes that underlie wars’ causes, their courses, and the challenges of postwar reconstruction. For us, then, the increasing academic division between feminist security studies (FSS) and feminist (international) political economy (FPE/FIPE) has been a cause for concern, and we welcomed Politics & Gender’s earlier Critical Perspectives section on efforts to bridge the two (June 2015). We noticed, however, that although violence was addressed in several of the special section's articles, war made only brief and somewhat peripheral appearances, and peacebuilding was all but absent. While three contributions (Hudson 2015; Sjoberg 2015; True 2015) mentioned the importance of political economy in the analysis of armed conflict, the aspects of war on which the articles focused were militarized sexualities (Sjoberg 2015) or conflict-related and postwar sexual and gender-based violence (Hudson 2015; True 2015).
Feminist Global Political Economy and Feminist Security Studies? The Politics of Delineating Subfields
Authors: Stern Maria
Published: November 2017

When considering possible conversations, synergies, overlaps, similarities, conflicts, and distinctions between two subfields or “camps” (Sylvester 2010), the question of limits looms large. Where, why, and how are the limits of feminist security studies (FSS) and feminist global political economy (FGPE) currently being drawn, and to what effect? Building upon previous conversations about the relationship between FSS and FGPE, particularly as they were discussed in the Critical Perspectives section in Politics & Gender (June 2015), as well as those about FSS and FGPE more generally, I briefly touch on a few central points regarding the politics of boundary drawing and the practices of feminist research.
Beyond the “Helpless Nepali Woman” versus the “Fierce Maoist Fighter”: Challenging the Artificial Security/Economy Divide
Authors: Kunz Rahel
Published: November 2017

Recent discussions over similarities and differences between feminist security studies (FSS) and feminist global political economy (FGPE) approaches invite us to reflect on the underlying assumptions about knowledge production within feminist international relations (IR) more broadly (Allison 2015; Enloe 2015; see also the introduction to this forum). I use Nepali women ex-combatants’ life stories to make two specific points relating to these discussions. First, I illustrate how the separation of security and political economy issues cannot fully account for their life experiences. Second, and by way of overcoming this separation, I show how by beginning with life stories, we can develop a holistic analysis that challenges the broader Eurocentric politics of feminist IR knowledge production.
Control of Glyphosate-Resistant Common waterhemp (Amaranthus rudis) in Three New Herbicide-Resistant Soybean Varieties in Ontario
Authors: Schryver Mike G. , Soltani Nader , Hooker David C. , Robinson Darren E. , Tranel Patrick J. , Sikkema Peter H.
Published: November 2017

Glyphosate-resistant (GR) common waterhemp (CW) is a localized weed in Ontario and one of the most problematic weeds in the US Corn Belt. First confirmed in Ontario in 2014, GR CW has now been confirmed in forty fields in three counties in Ontario as of 2015. Historically, the primary POST herbicides used for the control of CW in soybean were glyphosate, acifluorfen and fomesafen, but resistance to all three has been confirmed in many US states. Research was conducted in 2015 and 2016 to determine the control of GR CW with some of the new herbicide-resistant soybean technologies including glufosinate (LibertyLink), 2,4-D and glyphosate (Enlist), and isoxaflutole, mesotrione, and glufosinate (HPPD-resistant). Glyphosate-resistant CW was controlled (≥90%) all season with a two-pass weed control system across all herbicide-resistant soybean technologies evaluated. The two-pass weed control system in this research is defined as a PRE herbicide followed by a POST herbicide. At 12 WAA, the two-pass programs in LibertyLink, Enlist, and HPPD-resistant systems controlled GR CW up to 98, 98, and 92%, respectively, and reduced GR CW densities to 0 to 2% of the weedy control at 4 WAA. The two-pass programs provided greater GR CW control than PRE or POST herbicides alone. This study found that the use of two-pass weed control programs in glufosinate-resistant, glyphosate DMA/2,4-D choline-resistant and HPPD-resistant soybean can provide excellent control of GR CW, and can be valuable tools to reduce the selection intensity for herbicide-resistant weeds. Through the rotational use of different technologies, growers may be able to better manage their weed populations in reducing the risk of resistance when compared to the use of one herbicide repeatedly.
Benchmarking and Reconciliation of Time Series
Authors: Rojo-García José Luis , Sanz-Gómez José Antonio
Published: November 2017

Abstract. The present article features a hierarchical Bayes method applied to solving problems of benchmarking and contemporaneous reconciliation across time series. This method enables the use of high frequency series to be either approximations or one or several related indicators. This method may be applied when facing flow or index disaggregation problems. The authors compare their results to classical procedures (viz., Denton univariate and Rossi multivariate methods) through the use of indicators. This article concludes that the suggested method bestows greater importance on the low frequency series profile, consequently providing smoother solutions than its counterparts.
Sample Size Calculations for Testing Equivalence of Two Exponential Distributions With Right Censoring
Authors: Guo Jiin-Huarng , Luh Wei-Ming
Published: November 2017

Abstract. The present study considered two independent exponential distributions with the hypothesis for testing equivalence of lifetime means or failure rates, and aimed to determine the required uncensored sample size based on power, sampling cost, and censoring proportion simultaneously in the case of right censoring. Approximate sample size formulas with an iterative procedure were proposed and an uncensored sample size allocation ratio was derived to minimize the total cost for a designated power or maximize statistical power for a limit cost. R codes are provided for easy application. The proposed methods are validated in terms of Type I errors and statistical power in a simulation study, and are recommended for the future use.
The effects of PI3K-mediated signalling on glioblastoma cell behaviour
Authors: Langhans Julia , Schneele Lukas , Trenkler Nancy , von Bandemer Hélène , Nonnenmacher Lisa , Karpel-Massler Georg , Siegelin Markus D. , Zhou Shaoxia , Halatsch Marc-Eric , Debatin Klaus-Michael , Westhoff Mike-Andrew
Published: November 2017

The PI3K/Akt/mTOR signalling network is activated in almost 90% of all glioblastoma, the most common primary brain tumour, which is almost invariably lethal within 15 months of diagnosis. Despite intensive research, modulation of this signalling cascade has so far yielded little therapeutic benefit, suggesting that the role of the PI3K network as a pro-survival factor in glioblastoma and therefore a potential target in combination therapy should be re-evaluated. Therefore, we used two distinct pharmacological inhibitors that block signalling at different points of the cascade, namely, GDC-0941 (Pictilisib), a direct inhibitor of the near apical PI3K, and Rapamycin which blocks the side arm of the network that is regulated by mTOR complex 1. While both substances, at concentrations where they inhibit their primary target, have similar effects on proliferation and sensitisation for temozolomide-induced apoptosis, GDC-0941 appears to have a stronger effect on cellular motility than Rapamycin. In vivo GDC-0941 effectively retards growth of orthotopic transplanted human tumours in murine brains and significantly prolongs mouse survival. However, when looking at genetically identical cell populations that are in alternative states of differentiation, i.e. stem cell-like cells and their differentiated progeny, a more complex picture regarding the PI3K/Akt/mTOR pathway emerges. The pathway is differently regulated in the alternative cell populations and, while it contributes to the increased chemo-resistance of stem cell-like cells compared to differentiated cells, it only contributes to the motility of the latter. Our findings are the first to suggest that within a glioblastoma tumour the PI3K network can have distinct, cell-specific functions. These have to be carefully considered when incorporating inhibition of PI3K-mediated signals into complex combination therapies.
Downregulation of myostatin pathway in neuromuscular diseases may explain challenges of anti-myostatin therapeutic approaches
Authors: Mariot Virginie , Joubert Romain , Hourdé Christophe , Féasson Léonard , Hanna Michael , Muntoni Francesco , Maisonobe Thierry , Servais Laurent , Bogni Caroline , Le Panse Rozen , Benvensite Olivier , Stojkovic Tanya , Machado Pedro M. , Voit Thomas , Buj-Bello Ana , Dumonceaux Julie
Published: November 2017

Muscular dystrophies are characterized by weakness and wasting of skeletal muscle tissues. Several drugs targeting the myostatin pathway have been used in clinical trials to increase muscle mass and function but most showed limited efficacy. Here we show that the expression of components of the myostatin signaling pathway is downregulated in muscle wasting or atrophying diseases, with a decrease of myostatin and activin receptor, and an increase of the myostatin antagonist, follistatin. We also provide in vivo evidence in the congenital myotubular myopathy mouse model (knock-out for the myotubularin coding geneMtm1) that a down-regulated myostatin pathway can be reactivated by correcting the underlying gene defect. Our data may explain the poor clinical efficacy of anti-myostatin approaches in several of the clinical studies and the apparent contradictory results in mice regarding the efficacy of anti-myostatin approaches and may inform patient selection and stratification for future trials.
Optical charge state control of spin defects in 4H-SiC
Authors: Wolfowicz Gary , Anderson Christopher P. , Yeats Andrew L. , Whiteley Samuel J. , Niklas Jens , Poluektov Oleg G. , Heremans F. Joseph , Awschalom David D.
Published: November 2017

Defects in silicon carbide (SiC) have emerged as a favorable platform for optically active spin-based quantum technologies. Spin qubits exist in specific charge states of these defects, where the ability to control these states can provide enhanced spin-dependent readout and long-term charge stability. We investigate this charge state control for two major spin qubits in 4H-SiC, the divacancy and silicon vacancy, obtaining bidirectional optical charge conversion between the bright and dark states of these defects. We measure increased photoluminescence from divacancy ensembles by up to three orders of magnitude using near-ultraviolet excitation, depending on the substrate, and without degrading the electron spin coherence time. This charge conversion remains stable for hours at cryogenic temperatures, allowing spatial and persistent patterning of the charge state populations. We develop a comprehensive model of the defects and optical processes involved, offering a strong basis to improve material design and to develop quantum applications in SiC.
Super-radiance reveals infinite-range dipole interactions through a nanofiber
Authors: Solano P. , Barberis-Blostein P. , Fatemi F. K. , Orozco L. A. , Rolston S. L.
Published: November 2017

Atoms interact with each other through the electromagnetic field, creating collective states that can radiate faster or slower than a single atom, i.e., super- and sub-radiance. When the field is confined to one dimension it enables infinite-range atom–atom interactions. Here we present the first report of infinite-range interactions between macroscopically separated atomic dipoles mediated by an optical waveguide. We use cold 87Rb atoms in the vicinity of a single-mode optical nanofiber (ONF) that coherently exchange evanescently coupled photons through the ONF mode. In particular, we observe super-radiance of a few atoms separated by hundreds of resonant wavelengths. The same platform allows us to measure sub-radiance, a rarely observed effect, presenting a unique tool for quantum optics. This result constitutes a proof of principle for collective behavior of macroscopically delocalized atomic states, a crucial element for new proposals in quantum information and many-body physics.
A strategy for effective latent HIV reactivation using subtherapeutic drug doses
Authors: Cotterell James , Neely G. Gregory
Published: November 2017

Cell state switches underlie a plethora of biological phenomena and disease treatment strategies. Hence the ability to efficiently switch states in a chosen direction is of central importance in a number of scenarios. Increasing the concentration of an effector that results in a given switch is often limited by side effects. Approaches are thus increasingly sought to bypass these constraints, increasing the frequency of state switching without increasing the frequency of the side effect. Here, we employ dynamical systems theory to uncover a simple strategy as to how to maximize the probability of reactivating latent Human immunodeficiency virus (HIV) whilst maintaining minimal side effects. We demonstrate that continuous supply of an effector is significantly more likely to result in a switch with minimal side effects than the same effector supplied in temporally discrete doses. Importantly this continual dosage is likely to occur far below the Minimum effective dose at a concentration that has classically been thought subtherapeutic. We therefore suggest that in many interventional settings there exists potential to reduce drug dose much further than has previously been thought possible yet still maintaining efficacy.
Low-dose levels of bisphenol A inhibit telomerase via ER/GPR30-ERK signalling, impair DNA integrity and reduce cell proliferation in primary PBMC
Authors: Herz Corinna , Tran Hoai Thi Thu , Schlotz Nina , Michels Karin , Lamy Evelyn
Published: November 2017

Controversy exists about the human health risk of environmental exposure to bisphenol A (BPA). Telomerase activity is emerging both as biomarker and contributing factor for age-related diseases. The effects of BPA exposure at 1–1000 nM on telomerase, DNA integrity and cell proliferation were investigated in PBMC from human donors. Telomerase activity was determined by TRAP-ELISA assay and mRNA expression by qRT-PCR. Mechanistic studies were carried out on the ER/GPR30-ERK pathway using specific inhibitors/antagonists, the comet assay to quantify DNA damage and flow cytometry for cell proliferation. 24 h BPA exposure inhibited telomerase in a non-monotonic pattern with a peak inhibition of 32% at 1 nM (p ≤ 0.01). A significant telomerase inhibition was evident at 1 h after exposure with a minimum at 6 h. Elevated levels of DNA damage frequency and decrease in cell proliferation were evident upon long-term exposure. The results further demonstrate that BPA triggered rapidly an ER/GPR30-ERK transduction pathway that leads to decreased telomerase activity in human PBMC. This is the first study to demonstrate adverse impact of BPA at levels of current human exposure on telomerase in normal cells, mediated by ER/GPR30-ERK. The results suggest a potentially harmful influence of BPA on immune cells and should be addressed in future studies.
Adsorbed Conformations of PCE Superplasticizers in Cement Pore Solution Unraveled by Molecular Dynamics Simulations
Authors: Hirata Tsuyoshi , Ye Jun , Branicio Paulo , Zheng Jianwei , Lange Alex , Plank Johann , Sullivan Michael
Published: November 2017

The conformations of polycarboxylate ether (PCE) type superplasticizer polymers adsorbed on the surface of MgO in cement pore solution are simulated by molecular dynamics (MD). Three types of PCEs commonly applied to concrete are simulated, namely a methacrylate type PCE (PCEM-P), an allyl ether type PCE (PCEA-P), and an isoprenyl ether type PCE (PCEI-P) with ethylene oxide (EO) unit numbers (P) of 25, 34 and 25, respectively. It is observed that the adsorbed layer thickness is inversely proportional to the experimentally measured adsorbed amount at the initial paste flow of 26 ± 0.5 cm. Simulation results indicate that the adsorbed layer thickness is sensitive to the initial polymer orientations against the model MgO surface. I.e., polymer molecules initially placed parallel/perpendicularly against the MgO surface gradually forms a train shaped or a loop and tail adsorption profile, respectively. As a result, the loop and tail shaped conformation gives a higher layer thickness.
Protein-lysine methyltransferases G9a and GLP1 promote responses to DNA damage
Authors: Ginjala Vasudeva , Rodriguez-Colon Lizahira , Ganguly Bratati , Gangidi Prawallika , Gallina Paul , Al-Hraishawi Husam , Kulkarni Atul , Tang Jeremy , Gheeya Jinesh , Simhadri Srilatha , Yao Ming , Xia Bing , Ganesan Shridar
Published: November 2017

Upon induction of DNA breaks, ATM activation leads to a cascade of local chromatin modifications that promote efficient recruitment of DNA repair proteins. Errors in this DNA repair pathway lead to genomic instability and cancer predisposition. Here, we show that the protein lysine methyltransferase G9a (also known as EHMT2) and GLP1 (also known as EHMT1) are critical components of the DNA repair pathway. G9a and GLP1 rapidly localizes to DNA breaks, with GLP1 localization being dependent on G9a. ATM phosphorylation of G9a on serine 569 is required for its recruitment to DNA breaks. G9a catalytic activity is required for the early recruitment of DNA repair factors including 53BP and BRCA1 to DNA breaks. Inhibition of G9a catalytic activity disrupts DNA repair pathways and increases sensitivity to ionizing radiation. Thus, G9a is a potential therapeutic target in the DNA repair pathway.
Comprehensive high-throughput image analysis for therapeutic efficacy of architecturally complex heterotypic organoids
Authors: Bulin Anne-Laure , Broekgaarden Mans , Hasan Tayyaba
Published: November 2017

Bioengineered three-dimensional (3D) tumor models that incorporate heterotypic cellular communication are gaining interest as they can recapitulate key features regarding the intrinsic heterogeneity of cancer tissues. However, the architectural complexity and heterogeneous contents associated with these models pose a challenge for toxicological assays to accurately report treatment outcomes. To address this issue, we describe a comprehensive image analysis procedure for structurally complex organotypic cultures (CALYPSO) applied to fluorescence-based assays to extract multiparametric readouts of treatment effects for heterotypic tumor cultures that enables advanced analyses. The capacity of this approach is exemplified on various 3D models including adherent/suspension, mono-/heterocellular cultures and several disease types. The subsequent analysis revealed specific morphological effects of oxaliplatin chemotherapy, radiotherapy, and photodynamic therapy. The procedure can be readily implemented in most laboratories to facilitate high-throughput toxicological screening of pharmaceutical agents and treatment regimens on organotypic cultures of human disease to expedite drug and therapy development.
Up-regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice
Authors: Wang Yanyan , Lin Cai , Cao Yun , Duan Zhongliang , Guan Zhixun , Xu Jing , Zhu Xing-Quan , Xia Chaoming
Published: November 2017

The pathology of schistosome egg-induced liver granuloma, fibrosis and eventually liver scarring is complicated. CD4+ helper T (Th) cells play critical roles in both host humoral immunity and cellular immunity against parasitic infection and immunopathology in schistosomiasis. Follicular helper T (Tfh) cells are another specialized subset of Th cells and involved in infectious diseases. However, the immune regulatory mechanism of Tfh cells in severe liver pathology of schistosomiasis is still poorly understood. In this study, using a S. japonicum-infected mouse model, we studied the dynamics and effects of Tfh cells in vivo and demonstrated that Tfh phenotype molecules ICOS, PD-1 and functional factor IL-21 were positively correlated with disease development by flow cytometry. Meanwhile, our results also showed that Tfh cells enriched in splenic germinal center (GC) and promoted B cells producing IgM with the progress of hepatic immunopathology by B-T co-culture experiments. More importantly, our data indicated that IL-21 contributed to the formation and development of hepatic egg granuloma and subsequent fibrosis by driving GC responses and activating HSCs by immunohistochemical detection and blocking assay in vitro. Our findings contribute to the better understanding of the immunopathogenesis of schistosomiasis and have implications for therapeutic intervention of hepatic fibrotic diseases.
Regulation of ethylene-responsive SlWRKYs involved in color change during tomato fruit ripening
Authors: Wang Ling , Zhang Xue-lian , Wang Lu , Tian Yanan , Jia Ning , Chen Shuzhen , Shi Ning-bo , Huang Xuemei , Zhou Chu , Yu Yaowen , Zhang Zhao-qi , Pang Xue-qun
Published: November 2017

WRKY transcription factors (TFs) play important roles in stress responses in planta. However, the function of WRKY TFs in the regulation of fruit ripening is unclear. Here, 23 tomato SlWRKYs that are similar to ethylene-responsive WRKY genes from other plant species, or show up-regulation during fruit ripening in previous genome-wide study, were selected, and their function in fruit ripening was investigated. Twelve SlWRKYs were found to be responsive to ethylene (SlER-WRKYs), showing expression patterns similar to those of genes related to fruit ripening. Eight SlER-WRKYs—SlWRKY16, 17, 22, 25, 31, 33, 53, and 54, detected in the nuclei—interacted with and activated the promoters of 4 genes related to color change: Pheophytin Pheophorbide Hydrolase (SlPPH), Pheophorbide a Oxygenase (SlPAO), Phytoene Synthase 1 (SlPSY1) and Phytoene Desaturase (SlPDS). Yeast two-hybrid and bimolecular fluorescence complement (BiFC) assays in Arabidopsis protoplasts indicated that protein interactions occurred between SlWRKY17 and SlRIN, SlERF2b or SlERF7; SlWRKY33 and SlERF7; SlWRKY54 and SlERF2b; and SlWRKY16 and SlWRKY17. Suppression of SlWRKY 16, 17, 53 or 54 by virus-induced gene silencing (VIGS) retarded the red coloration of the fruit. Our study provides comprehensive molecular evidence that WRKY TFs function in fruit ripening, particularly in color change, and are linked to the intricate regulatory network of other ripening regulators.