bluuebunny/crossref_metadata_2025 huggingface dataset:
The Lofoten Basin eddy: Three years of evolution as observed by Seagliders
Authors: Yu Lu‐Sha , Bosse Anthony , Fer Ilker , Orvik Kjell A. , Bruvik Erik M. , Hessevik Idar , Kvalsund Karsten
Published: July 2017

The Lofoten Basin in the Norwegian Sea is an area where the warm Atlantic Water is subject to the greatest heat losses anywhere in the Nordic Seas. A long‐lived, deep, anticyclonic eddy is located in the central part of the basin (the Lofoten Basin Eddy, LBE). Here we use observations from Seagliders, collected between July 2012 and July 2015, to describe LBE in unprecedented detail. The missions were designed to sample LBE repeatedly, allowing for multiple realizations of radial sections across the eddy. LBE has a mean radius of 18 ± 4 km and propagates cyclonically with a mean speed of approximately 3–4 cm s−1. The anticyclonic azimuthal peak velocity varies between 0.5 and 0.7 m s−1, located between 700 and 900 m depth. The average contribution of geostrophy in the cyclogeostrophic balance is 44%. The relative vorticity of the core is close to the local Coriolis parameter. The evolution of core water properties shows substantial interannual variability, influenced by surface buoyancy flux and advection of anomalous low‐salinity near‐surface waters that may affect the vertical extent of winter convection. A comparison of the eddy properties to those inferred from automated tracking of satellite altimeter observations shows that the location of eddy center is successfully detected to within one half eddy radius, but vorticity is underestimated and the radius overestimated, each approximately by a factor of 2, because of excessive smoothing relative to the small eddy radius.
New insights about cloud vertical structure from CloudSat and CALIPSO observations
Authors: Oreopoulos Lazaros , Cho Nayeong , Lee Dongmin
Published: July 2017

Active cloud observations from A‐Train's CloudSat and CALIPSO satellites offer new opportunities to examine the vertical structure of hydrometeor layers. We use the 2B‐CLDCLASS‐LIDAR merged CloudSat‐CALIPSO product to examine global aspects of hydrometeor vertical stratification. We group the data into major cloud vertical structure (CVS) classes based on our interpretation of how clouds in three standard atmospheric layers overlap and provide their global frequency of occurrence. The two most frequent CVS classes are single‐layer (per our definition) low and high clouds that represent ~53% of cloudy skies, followed by high clouds overlying low clouds, and vertically extensive clouds that occupy near‐contiguously a large portion of the troposphere. The prevalence of these configurations changes seasonally and geographically, between daytime and nighttime, and between continents and oceans. The radiative effects of the CVS classes reveal the major radiative warmers and coolers from the perspective of the planet as a whole, the surface, and the atmosphere. Single‐layer low clouds dominate planetary and atmospheric cooling and thermal infrared surface warming. We also investigate the consistency between passive and active views of clouds by providing the CVS breakdowns of Moderate Resolution Imaging Spectroradiometer cloud regimes for spatiotemporally coincident MODIS‐Aqua (also on the A‐Train) and CloudSat‐CALIPSO daytime observations. When the analysis is expanded for a more in‐depth look at the most heterogeneous of the MODIS cloud regimes, it ultimately confirms previous interpretations of their makeup that did not have the benefit of collocated active observations.
Analysis of remotely sensed and surface data of aerosols and meteorology for the Mexico Megalopolis Area between 2003 and 2015
Authors: Mora Marco , Braun Rachel A. , Shingler Taylor , Sorooshian Armin
Published: July 2017

This paper presents an aerosol characterization study from 2003 to 2015 for the Mexico City Metropolitan Area using remotely sensed aerosol data, ground‐based measurements, air mass trajectory modeling, aerosol chemical composition modeling, and reanalysis data for the broader Megalopolis of Central Mexico region. The most extensive biomass burning emissions occur between March and May concurrent with the highest aerosol optical depth, ultraviolet aerosol index, and surface particulate matter (PM) mass concentration values. A notable enhancement in coarse PM levels is observed during vehicular rush hour periods on weekdays versus weekends owing to nonengine‐related emissions such as resuspended dust. Among wet deposition species measured, PM2.5, PM10, and PMcoarse (PM10‐PM2.5) were best correlated with NH4+, SO42−, and Ca2+, suggesting that the latter three constituents are important components of the aerosol seeding raindrops that eventually deposit to the surface in the study region. Reductions in surface PM mass concentrations were observed in 2014–2015 owing to reduced regional biomass burning as compared to 2003–2013.
Contrasting effect of Saharan dust and UVR on autotrophic picoplankton in nearshore versus offshore waters of Mediterranean Sea
Authors: González‐Olalla J. M. , Medina‐Sánchez J. M. , Cabrerizo M. J. , Villar‐Argáiz Manuel , Sánchez‐Castillo Pedro M. , Carrillo Presentación
Published: July 2017

Autotrophic picoplankton (APP) is responsible for the vast majority of primary production in oligotrophic marine areas, such as the Alboran Sea. The increase in atmospheric dust deposition (e.g., from Sahara Desert) associated with global warming, together with the high UV radiation (UVR) on these ecosystems, may generate effects on APP hitherto unknown. We performed an observational study across the Alboran Sea to establish which factors control the abundance and distribution of APP, and we made a microcosm experiment in two distinct areas, nearshore and offshore, to predict the joint UVR × dust impact on APP at midterm scales. Our observational study showed that temperature (T) was the main factor explaining the APP distribution whereas total dissolved nitrogen positively correlated with APP abundance. Our experimental study revealed that Saharan dust inputs reduced or inverted the UVR damage on the photosynthetic quantum yield (ΦPSII) and picoplanktonic primary production (PPP) in the nearshore area but accentuated it in the offshore. This contrasting effect is partially explained by the nonphotochemical quenching, acting as a photorepair mechanism. Picoeukaryotes reflected the observed effects on the physiological and metabolic variables, and Synechococcus was the only picoprokaryotic group that showed a positive response under UVR × dust conditions. Our study highlights a dual sensitivity of nearshore versus offshore picoplankton to dust inputs and UVR fluxes, just at the time in which these two global‐change factors show their highest intensities and may recreate a potential future response of the microbial food web under global‐change conditions.
A Self‐Transformable pH‐Driven Membrane‐Anchoring Photosensitizer for Effective Photodynamic Therapy to Inhibit Tumor Growth and Metastasis
Authors: Luo Guo‐Feng , Chen Wei‐Hai , Hong Sheng , Cheng Qian , Qiu Wen‐Xiu , Zhang Xian‐Zheng
Published: July 2017

Poor tumor selectivity and short life span of reactive oxygen species (ROS) are two major challenges in photodynamic therapy (PDT). In this study, a self‐transformable pH‐driven membrane anchoring photosensitizer (pHMAPS) is used to realize tumor‐specific accumulation and in situ PDT on tumor cell membrane to maximize the therapeutic potency. It is found that pHMAPS was able to form α‐helix structure under acidic condition (pH 6.5 or 5.5), while remain random coil at normal pH of 7.4. This pH‐driven secondary structure switch enables the successful insertion of pHMAPS into membrane lipid bilayer, especially for cancerous cell membrane in the acidic tumor microenvironment. Under laser irradiation, cytotoxic ROS is generated in the immediate vicinity of cell membrane, resulting in superior cell killing effect in vitro and significant inhibition of tumor growth in vivo. Importantly, benefited from this membrane‐specific PDT, tumor growth‐induced hepatic, pulmonary, as well as osseous metastases of breast cancer cells are also retarded after PDT treatment. Thus, the membrane localized PDT by pHMAPS provides a simple but effective strategy to enhance the medical performance of photosensitizing agents in cancer therapy.
Freeze‐Drying as a Novel Biofabrication Method for Achieving a Controlled Microarchitecture within Large, Complex Natural Biomaterial Scaffolds
Authors: Brougham Claire M. , Levingstone Tanya J. , Shen Nian , Cooney Gerard M. , Jockenhoevel Stefan , Flanagan Thomas C. , O'Brien Fergal J.
Published: July 2017

The biofabrication of large natural biomaterial scaffolds into complex 3D shapes which have a controlled microarchitecture remains a major challenge. Freeze‐drying (or lyophilization) is a technique used to generate scaffolds in planar 3D geometries. Here we report the development of a new biofabrication process to form a collagen‐based scaffold into a large, complex geometry which has a large height to width ratio, and a controlled porous microarchitecture. This biofabrication process is validated through the successful development of a heart valve shaped scaffold, fabricated from a collagen‐glycosaminoglycan co‐polymer. Notably, despite the significant challenges in using freeze‐drying to create such a structure, the resultant scaffold has a uniform, homogenous pore architecture throughout. This is achieved through optimization of the freeze‐drying mold and the freezing parameters. We believe this to be the first demonstration of using freeze‐drying to create a large, complex scaffold geometry with a controlled, porous architecture for natural biomaterials. This study validates the potential of using freeze‐drying for development of organ‐specific scaffold geometries for tissue engineering applications, which up until now might not have been considered feasible.
Amino‐Mediated Anchoring Perovskite Quantum Dots for Stable and Low‐Threshold Random Lasing
Authors: Li Xiaoming , Wang Yue , Sun Handong , Zeng Haibo
Published: July 2017

Halide perovskite quantum dots (Pe‐QDs) have been considered as outstanding candidates for photodetector, light‐emitting diode, and lasing applications, but these perspectives are being impeded by the severe stability, including both chemical and optical degradations. This study reports on amino‐mediated anchoring Pe‐QDs onto the surfaces of monodisperse silica to effectively depress the optical degradation of their photoluminescence (PL) and random lasing stabilities, hence achieving highly stable and low‐threshold lasing. An amination‐mediated nucleation and growth process is designed for the general and one‐pot synthesis of Pe‐QDs on the surfaces of silica spheres. The facile synthetic process, which can be finished within several minutes, insures scalable production. Surprisingly, almost no PL degradation is observed after 40 d storage under ambient conditions, even 80% PL intensity can be maintained after persistently illuminated by UV lamps for 108 h. Subsequently, extremely stable random lasing is achieved after storage for 2 months or over continuously optical pumping for 8 h. Such high PL and lasing stabilities originate from the isolation effects due to the effective anchoring, which separate the Pe‐QDs from each other and inhibit the photoinduced regrowth and deterioration. This work will also open the window of perovskite‐based multifunctional systems.
Questions and Answers on the Wettability of Nano‐Engineered Surfaces
Authors: MacGregor‐Ramiasa Melanie N. , Vasilev Krasimir
Published: July 2017

Surface roughening has long been used to confer materials remarkable wetting properties, such as super hydrophobicity. When roughness belongs to the microscale, existing models can, to some extent, explain and predict real‐world wetting states. With the advent of nanotechnology, however, a multitude of nano‐engineered materials are being developed and unexpected wetting behaviors have been observed which cannot be described by conventional theories. While it is clear that advanced nanotextured materials are essential to a vast range of ground breaking technologies, the intricate mechanisms governing the wetting of such surfaces—at the limit of validity of continuum theories—also need to be clarified. This review aims at presenting what is known and what remains to be discovered about the wettability of nanoengineered materials. The advantages and uniqueness of nanostructured substrates is highlighted first, with a focus on practical applications benefitting from the distinctive wetting properties of nanorough substrates. Classic wetting theories and their limitations are briefly discussed, before describing with a top down vision, why the wetting of nanostructured substrates differ from that of microtextured surfaces. Recent experimental and theoretical studies which contributed to the progress in this field are considered, before outlining potential future areas of research.
Solving the Scaling Issue of Increasing Forming Voltage in Resistive Random Access Memory Using High‐k Spacer Structure
Authors: Tseng Yi‐Ting , Chen Po‐Hsun , Chang Ting‐Chang , Chang Kuan‐Chang , Tsai Tsung‐Ming , Shih Chih‐Cheng , Huang Hui‐Chun , Yang Cheng‐Chi , Lin Chih‐Yang , Wu Cheng‐Hsien , Zheng Hao‐Xuan , Zhang Shengdong , Sze Simon M.
Published: July 2017

In this study, the rising forming voltage issue during device cell scale‐down in resistance random access memory (RRAM) is solved by introducing new high‐permittivity (high‐k) material as the side‐wall spacer structure, unlike the normally used low‐permittivity (low‐k) material. Simulated electrical fields based on COMSOL Multiphysics software results suggest a RRAM device with a high‐k spacer effectively confines the electric field. The effects of this confined electric field are notable, especially when the device cell is scaled down. The device fabrication process is modified to incorporate the high‐k sidewall. Cross‐sectional transmission electron microscopy imaging confirms the existence of SiO2 and HfO2 as the spacer structures in two different devices. Electrical measurements of forming voltages ranging from 1 to 0.16 µm2 are conducted to verify the effects. Statistical measurements confirm that the forming voltages of the devices with high‐k material as sidewall do not increase with a reduction in device cell size. Moreover, reliability tests, including endurance and retention for the high‐k sidewall device, also exhibit very stable resistance switching characteristics. As a result, the structure that is proposed successfully solves the forming voltage issues within small device cells in RRAM without any cost to device reliability.
High Intensity Generation of Entangled Photons in a Two‐Mode Electromagnetic Field
Authors: Makarov D. N.
Published: July 2017

At present, the sources of entangled photons have a low rate of photon generation. This limitation is a key component of quantum informatics for the realization of such functions as linear quantum computation and quantum teleportation. In this paper, we propose a method for high intensity generation of entangled photons in a two‐mode electromagnetic field. On the basis of exact solutions of the Schrödinger equation, when electrons interact in an atom with a strong two‐mode electromagnetic field, it is shown that there may be large quantum entanglement between photons. The quantum entanglement is analyzed on the basis of the Schmidt parameter. It is shown that the Schmidt parameter can reach very high values depending on the choice of characteristics of the two‐mode fields. We find the Wigner function for the considered case. Violation of Bell's inequalities for continuous variables is demonstrated.
Quantum Transition Between Magnetically Ordered and Mott Glass Phases
Authors: Syromyatnikov A. V.
Published: July 2017

We discuss a quantum transition from a superfluid to a Mott glass phases in disordered Bose‐systems by the example of an isotropic spin‐ antiferromagnet with spatial dimension and with disorder in tunable exchange couplings. Our analytical consideration is based on general properties of a system in critical regime, on the assumption that the magnetically order part of the system shows fractal properties near the transition, and on a hydrodynamic description of long‐wavelength magnons in the magnetically ordered (“superfluide”) phase. Our results are fully consistent with a scaling theory based on an ansatz for the free energy proposed by M. P. Fisher et al. (Phys. Rev. B 40, 546 (1989)). We obtain for the dynamical critical exponent and , where ϕ, β, and ν are critical exponents of the critical temperature, the order parameter, and the correlation length, respectively. The density of states of localized excitations (fractons) is found to show a superuniversal (i.e., independent of d) behavior.
1D and 2D Graphdiynes: Recent Advances on the Synthesis at Interfaces and Potential Nanotechnological Applications
Authors: Chen Zhi , Molina‐Jirón Concepción , Klyatskaya Svetlana , Klappenberger Florian , Ruben Mario
Published: July 2017

In solution‐based chemistry butadiyne linkage through the homocoupling reaction of alkynes is a versatile tool for the synthesis of π‐conjugated polymers, scaffolds and networks. To date this strategy was actively implemented towards chemical synthesis at interfaces. In this review paper we summarize recent advances in the syntheses of 1D wires, 2D single‐layers and thin films of graphdiyne‐related carbon materials at interfaces and their potential applications in nanotechnology. With a high degree of π‐conjunction, uniformly distributed pores and tunable electronic properties such 2D all‐carbon networks with butadiyne linkages also known as ‘graphdiynes’ have been successfully employed in the field‐effected emission devices, solar cells, for Li ion storage and oil water separation, and as catalysis or chemical sensors.
Metall‐Metall‐Mehrfachbindung oder keine Bindung? Die elektronische Struktur von V2O2
Authors: Hübner Olaf , Himmel Hans‐Jörg
Published: July 2017

Die detaillierte Kenntnis der elektronischen Struktur von Vanadiumoxidclustern bildet die Basis für das Verständnis und die Abstimmung ihrer wichtigen katalytischen Eigenschaften. Allerdings existieren in der Literatur schon für das einfache vieratomige V2O2‐Molekül widersprüchliche Berichte bezüglich des elektronischen Grundzustandes und einer möglichen Vanadium‐Vanadium‐Bindung. Mit einer Kombination aus experimentellen (Matrixisolation) und theoretischen Ergebnissen zeigen wir hier, dass eine Vanadium‐Vanadium‐Bindung in diesem prototypischen Vanadiumoxidmolekül gebildet wird.
Rheological behaviors exhibited by soy protein systems under dynamic aqueous environments
Authors: Garrity Nancy K. , Grigsby Warren J. , Jin Jianyong , Edmonds Neil R.
Published: July 2017

In this study, rheological behaviors of soy protein and soy flour as powders, pastes, and dispersions are characterized over a range of water contents and temperature to understand their processing in adhesives or paints. At ambient temperature, soy protein samples were characterized by low critical strain values (<0.1%), whereas soy flour samples exhibit linear viscoelastic regions >1% strain with 30–90% water content. On heating, the aqueous soy protein and soy flour compositions have complex rheological behaviors due to plasticization by water and the thermal denaturing and crosslinking of protein and carbohydrate with increasing temperature. Below 100 °C, soy protein rheological behaviors were attributable to the glass transition of the 7S and 11S soy globulin fractions, polymer flow, and plasticization by residual moisture. Above 100 °C, the onset of protein crosslinking was observed with this shifting to higher temperatures for samples still dehydrating. With soy flour samples, the residual moisture present above 100 °C similarly increase protein crosslinking to higher temperatures (125–148 °C) for samples with initial water contents of 30–90%. These results provide a basis for understanding why soy systems undergoing heat processing and rapid dehydration will require higher temperature and longer processing time to attain a cured, crosslinked state. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45513.
Validation of clay modeling as a learning tool for the periventricular structures of the human brain
Authors: Akle Veronica , Peña‐Silva Ricardo A. , Valencia Diego M. , Rincón‐Perez Carlos W.
Published: July 2017

Visualizing anatomical structures and functional processes in three dimensions (3D) are important skills for medical students. However, contemplating 3D structures mentally and interpreting biomedical images can be challenging. This study examines the impact of a new pedagogical approach to teaching neuroanatomy, specifically how building a 3D‐model from oil‐based modeling clay affects learners’ understanding of periventricular structures of the brain among undergraduate medical students in Colombia. Students were provided with an instructional video before building the models of the structures, and thereafter took a computer‐based quiz. They then brought their clay models to class where they answered questions about the structures via interactive response cards. Their knowledge of periventricular structures was assessed with a paper‐based quiz. Afterward, a focus group was conducted and a survey was distributed to understand students’ perceptions of the activity, as well as the impact of the intervention on their understanding of anatomical structures in 3D. Quiz scores of students that constructed the models were significantly higher than those taught the material in a more traditional manner (P < 0.05). Moreover, the modeling activity reduced time spent studying the topic and increased understanding of spatial relationships between structures in the brain. The results demonstrated a significant difference between genders in their self‐perception of their ability to contemplate and rotate structures mentally (P < 0.05). The study demonstrated that the construction of 3D clay models in combination with autonomous learning activities was a valuable and efficient learning tool in the anatomy course, and that additional models could be designed to promote deeper learning of other neuroanatomy topics. Anat Sci Educ 11: 137–145. © 2017 American Association of Anatomists.
Stochastic reranking of biomedical search results based on extracted entities
Authors: Fafalios Pavlos , Tzitzikas Yannis
Published: July 2017

Health‐related information is nowadays accessible from many sources and is one of the most searched‐for topics on the Internet. However, existing search systems often fail to provide users with a good list of medical search results, especially for classic (keyword‐based) queries. In this article we elaborate on whether and how we can exploit biomedicine‐related entities from the emerging Web of Data for improving (through reranking) the results returned by a search system. The aim is to promote relevant but low‐ranked hits containing entities that are important to the current search context. We introduce an approach that is based on entity extraction applied on the retrieved documents, yielding a graph of documents along with entities, which in turn is analyzed probabilistically using a Random Walk‐based method. The proposed approach is independent of the submitted query and the underlying retrieval models, and thus can be applied over any ranked list of medical search results. Evaluation results using the data set of TREC Clinical Decision Support track demonstrate that the proposed approach can significantly improve the results returned by classic and widely applicable retrieval models. The results also enabled us to identify cases where the proposed reranking method fails to improve the ranking.
Metabolism of 7‐ethoxycoumarin, flavanone and steroids by cytochrome P450 2C9 variants
Authors: Uno Tomohide , Nakano Ryosuke , Kanamaru Kengo , Takenaka Shinji , Uno Yuichi , Imaishi Hiromasa
Published: July 2017

CYP2C9 is a human microsomal cytochrome P450c (CYP). Much of the variation in CYP2C9 levels and activity can be attributed to polymorphisms of this gene. Wild‐type CYP2C9 and mutants were coexpressed with NADPH‐cytochrome P450 reductase in Escherichia coli. The hydroxylase activities toward 7‐ethoxycoumarin, flavanone and steroids were examined. Six CYP2C9 variants showed Soret peaks (450 nm) typical of P450 in reduced CO‐difference spectra. CYP2C9.38 had the highest 7‐ethoxycoumarin de‐ethylase activity. All the CYP2C9 variants showed lower flavanone 6‐hydroxylation activities than CYP2C9.1 (the wild‐type). CYP2C9.38 showed higher activities in testosterone 6β‐hydroxylation, progesterone 6β−/16α‐hydroxylation, estrone 11α‐hydroxylation and estradiol 6α‐hydroxylation than CYP2C9.1. CYP2C9.40 showed higher testosterone 17‐oxidase activity than CYP2C9.1; CYP2C9.8 showed higher estrone 16α‐hydroxylase activity and CYP2C9.12 showed higher estrone 11α‐hydroxylase activity. CYP2C9.9 and CYP2C9.10 showed similar activities to CYP2C9.1. These results indicate that the substrate specificity of CYP2C9.9 and CYP2C9.10 was not changed, but CYP2C9.8, CYP2C9.12 and CYP2C9.40 showed different substrate specificity toward steroids compared with CYP2C9.1; and especially CYP2C9.38 displayed diverse substrate specificities towards 7‐ethoxycoumarin and steroids.
A Sensitive Luminescent Acetylacetone Probe Based on Zn‐MOF with Six‐Fold Interpenetration
Authors: Kang Xiao‐Min , Cheng Rui‐Rui , Xu Hang , Wang Wen‐Min , Zhao Bin
Published: July 2017

A novel metal‐organic framework {[Zn(XL)2](ClO4)2⋅6 H2O}n (XL=N,N′‐bicyclo[2.2.2]oct‐7‐ene‐2,3,5,6‐tetracarboxdiimide bi(1,2,4‐triazole)) was synthesized and structurally characterized, presenting the first example of six‐fold interpenetrating 3 D framework with the topology type of sqc6, which displays high thermostability and solvent stability. Additionally, the luminescence investigations reveal that this MOF can sensitively and selectively detect acetylacetone with a detection limit of 1.72 ppm. More importantly, it is rather rare for an MOF‐based luminescence probe to serve as a sensor to effectively detect acetylacetone.
Dissecting Trichalcogenasumanenes: π‐Bowl to Planar, Invertible Curvature, and Chiral Polycycles
Authors: Hou Xueqing , Li Xuexiang , Sun Chunlin , Chen Lichuan , Sun Yantao , Liu Zhe , Zhang Hao‐Li , Shao Xiangfeng
Published: July 2017

The buckybowl trichalcogenasumanenes show cleavage of flanking benzene ring upon oxidation, which leads their dissection by fusing various amidine moieties onto peripheral region. By gradually increasing the ring size of amidine from five‐ to six‐ and seven‐membered, the molecule engineering results in the [7‐5‐6]‐, [7‐6‐6]‐, and [7‐7‐6]‐fused polycycles. Three systems are distinct in the molecular geometries, packing motifs, and optoelectronic properties. The [7‐5‐6]‐fused case adopts the flat backbone, displays strong emission with the fluorescence quantum yield up to 52.3 %, and undergoes a two‐photon absorption process. The [7‐6‐6]‐fused one is of a curvature with molecular geometry inversion, forms a tight stack of curved π‐system, shows broad absorption extended to 700 nm, and exhibits the p‐type semiconducting behavior with hole mobility of 4.4×10−3 cm2 V−1 s−1. The [7‐7‐6]‐fused one possesses the highly twisted skeleton to show stable chirality, and exhibits red emission in both solution and solid state. The surgery on trichalcogenasumanene is a promising approach to create polycycles with diverse functionalities.
A call for action: Increasing enrollment of untreated patients with higher‐risk myelodysplastic syndromes in first‐line clinical trials
Authors: Zeidan Amer M. , Stahl Maximilian , Sekeres Mikkael A. , Steensma David P. , Komrokji Rami S. , Gore Steven D.
Published: July 2017

Hypomethylating agents (HMAs) have changed the landscape of the management of patients with higher‐risk myelodysplastic syndromes (HR‐MDS). HMAs have improved hematopoiesis and quality of life and, in the case of azacitidine, prolonged survival in a large randomized trial. However, multiple real‐life and registry analyses have demonstrated minimal survival gains at the population level after the approval of HMAs. Furthermore, the 24‐month median survival observed with azacitidine in the landmark AZA‐001 trial has not been replicated in population‐based studies or in other clinical trials using azacitidine monotherapy arms. Herein, we critically review the accumulating data suggesting that the actual survival impact of HMAs, especially azacitidine, in patients with HR‐MDS is significantly lower than what was observed in the AZA‐001 trial and what often is quoted to patients, and discuss the potential explanations for this discrepancy. We also present the rationale for why front‐line clinical trial enrollment should be always considered and discussed with every newly diagnosed patient with HR‐MDS rather than defaulting to the routine use of HMAs. Finally, we review the challenges to wider‐scale enrollment in front‐line HR‐MDS clinical trials and suggest solutions to accelerate this process with the ultimate goal of achieving a real and substantial change in the natural history of this aggressive malignancy. Cancer 2017;123:3662–3672. © 2017 American Cancer Society
Next‐generation learning and training: The Cy‐TEST experience
Authors: Fassina Ambrogio , Cappellesso Rocco , Tötsch Martin , Barroca Helena , Marchiò Caterina , Dina Roberto , Ovcin Emanuela , Bussolati Gianni
Published: July 2017

On the basis of pioneering achievements with Cy‐TEST, it is possible that a new era of learning, training, and testing in cytopathology and histopathology is coming.
Distribution and chemical composition of estrogen receptor β neurons in the paraventricular nucleus of the female and male mouse hypothalamus
Authors: Oyola Mario G. , Thompson Maranda K. , Handa Aaron Z. , Handa Robert J.
Published: July 2017

Activation of estrogen receptor beta (ERβ)‐expressing neurons regulates the mammalian stress response via the hypothalamic–pituitary–adrenal (HPA) axis. These neurons densely populate the paraventricular nucleus of the hypothalamus (PVN). Recent research has revealed striking differences between rat and mouse PVN cytochemistry, but careful exploration of PVN ERβ neurons in mice has been hindered by a lack of specific ERβ antisera. Therefore, we used male and female transgenic mice expressing EGFP under the control of the mouse ERβ promoter (ERβ‐EGFP) to examine the chemical architecture of PVN ERβ cells. Using immunohistochemistry, we found that 90% of ERβ‐immunoreactivity (‐ir) colocalized with EGFP. Cellular colocalization of EGFP with neuropeptides, transcription modulators, and neuronal tracers was examined throughout the PVN. ERβ‐EGFP cells expressed oxytocin more abundantly in the rostral (71 ± 3%) than caudal (33 ± 8%) PVN. Arginine vasopressin colocalized with EGFP more often in females (18 ± 3%) than males (4 ± 1%). Moreover, estrogen receptor α‐ir colocalized with ERβ‐EGFP at low levels (15 ± 3%). Using a corticotropin releasing hormone‐cre driver X tdTomato reporter mouse, we found a moderate colocalization with ERβ‐ir (48 ± 16%) in the middle PVN. Peripheral injection of fluorogold revealed that the rostral PVN ERβ‐EGFP cells are neuroendocrine neurons whereas non‐neuroendocrine (presumably pre‐autonomic) ERβ‐EGFP neurons predominated in the posterior PVN. These data demonstrate chemoarchitectural differences in ERβ neurons of the mouse PVN that are different from that previously described for the rat, thus, elucidating potential neuronal pathways involved in the regulation of the HPA axis in mice.
Volume Estimates on the Critical Sets of Solutions to Elliptic PDEs
Authors: Naber Aaron , Valtorta Daniele
Published: July 2017

In this paper we study solutions to elliptic linear equations

urn:x-wiley:00103640:media:cpa21708:cpa21708-math-0001

either on or a Riemannian manifold, under the assumption that the coefficient functions aij are Lipschitz bounded. We focus our attention on the critical set and the singular set , and more importantly on effective versions of these. Currently, with just the Lipschitz regularity of the coefficients, the strongest results in the literature say that the singular set is (n–2)–dimensional; however, at this point it has not even been shown that unless the coefficients are smooth. Fundamentally, this is due to the need of an ɛ‐regularity theorem that requires higher smoothness of the coefficients as the frequency increases. We introduce new techniques for estimating the critical and singular set, which avoids the need of any such ɛ‐regularity. Consequently, we prove that if the frequency of u is bounded by Λ, then we have the estimates and , depending on whether the equation is critical or not. More importantly, we prove corresponding estimates for the effective critical and singular sets. Even under the assumption of real analytic coefficients these results are much sharper than those currently in the literature. We also give applications of the technique to give estimates on the volume of the nodal set of solutions and estimates for the corresponding eigenvalue problem.© 2017 Wiley Periodicals, Inc.
Revisiting Hansen Solubility Parameters by Including Thermodynamics
Authors: Louwerse Manuel J. , Maldonado Ana , Rousseau Simon , Moreau‐Masselon Chloe , Roux Bernard , Rothenberg Gadi
Published: July 2017

The Hansen solubility parameter approach is revisited by implementing the thermodynamics of dissolution and mixing. Hansen's pragmatic approach has earned its spurs in predicting solvents for polymer solutions, but for molecular solutes improvements are needed. By going into the details of entropy and enthalpy, several corrections are suggested that make the methodology thermodynamically sound without losing its ease of use. The most important corrections include accounting for the solvent molecules’ size, the destruction of the solid's crystal structure, and the specificity of hydrogen‐bonding interactions, as well as opportunities to predict the solubility at extrapolated temperatures. Testing the original and the improved methods on a large industrial dataset including solvent blends, fit qualities improved from 0.89 to 0.97 and the percentage of correct predictions rose from 54 % to 78 %. Full Matlab scripts are included in the Supporting Information, allowing readers to implement these improvements on their own datasets.
Dose‐Exposure‐Response Relationship of the Investigational Anti‐Interleukin‐13 Monoclonal Antibody Tralokinumab in Patients With Severe, Uncontrolled Asthma
Authors: Baverel Paul G. , White Nicholas , Vicini Paolo , Karlsson Mats O. , Agoram Balaji
Published: July 2017

Interleukin (IL)‐13 is involved in the pathogenesis of some types of asthma. Tralokinumab is a human immunoglobulin G4 monoclonal antibody that specifically binds to IL‐13. Two placebo‐controlled phase II studies (phase IIa, NCT00873860 and phase IIb, NCT01402986) have been conducted in which tralokinumab was administered subcutaneously. This investigation aimed to characterize tralokinumab's dose‐exposure‐response (forced expiratory volume in 1 s (FEV1)) relationship in patients with asthma and to predict the most appropriate dose for phase III. An integrated population pharmacokinetic‐pharmacodynamic (PK/PD) modeling analysis was required for phase III dose selection, due to differing phase II patient populations, designs, and regimens. Analysis of combined datasets enabled the identification of tralokinumab's dose‐exposure‐FEV1 response relationship in patients with asthma. Near‐maximal FEV1 increase was predicted at a dose of 300 mg SC once every 2 weeks (Q2W). This dose was chosen for tralokinumab in the phase III clinical development program for treatment of severe, uncontrolled asthma.
How relative size and abundance structures the relationship between size and individual growth in an ontogenetically piscivorous fish
Authors: Chamberlin Joshua W. , Beckman Brian R. , Greene Correigh M. , Rice Casimir A. , Hall Jason E.
Published: July 2017

While individual growth ultimately reflects the quality and quantity of food resources, intra and interspecific interactions for these resources, as well as individual size, may have dramatic impacts on growth opportunity. Out‐migrating anadromous salmonids make rapid transitions between habitat types resulting in large pulses of individuals into a given location over a short period, which may have significant impact on demand for local resources. We evaluated the spatial and temporal variation in IGF‐1 concentrations (a proxy for growth rate) and the relationship between size and concentration for juvenile Chinook salmon in Puget Sound, WA, USA, as a function of the relative size and abundance of both Chinook salmon and Pacific herring, a species which commonly co‐occurs with salmonids in nearshore marine habitats. The abundance of Chinook salmon and Pacific herring varied substantially among the sub‐basins as function of outmigration timing and spawn timing, respectively, while size varied systematically and consistently for both species. Mean IGF‐1 concentrations were different among sub‐basins, although patterns were not consistent through time. In general, size was positively correlated with IGF‐1 concentration, although the slope of the relationship was considerably higher where Pacific herring were more abundant than Chinook salmon; specifically where smaller individual herring, relative to Chinook salmon, were more abundant. Where Pacific herring were less abundant than Chinook salmon, IGF‐1 concentrations among small and large Chinook salmon were more variable and showed no consistent increase for larger individuals. The noticeable positive effect of relative Pacific herring abundance on the relationship between size and individual growth rates likely represents a shift to predation based on increased IGF‐1 concentrations for individual Chinook salmon that are large enough to incorporate fish into their diet and co‐occur with the highest abundances of Pacific herring.
The influence of herbivory and weather on the vital rates of two closely related cactus species
Authors: Sauby Kristen E. , Kilmer John , Christman Mary C. , Holt Robert D. , Marsico Travis D.
Published: July 2017

Herbivory has long been recognized as a significant driver of plant population dynamics, yet its effects along environmental gradients are unclear. Understanding how weather modulates plant–insect interactions can be particularly important for predicting the consequences of exotic insect invasions, and an explicit consideration of weather may help explain why the impact can vary greatly across space and time. We surveyed two native prickly pear cactus species (genus Opuntia) in the Florida panhandle, USA, and their specialist insect herbivores (the invasive South American cactus moth, Cactoblastis cactorum, and three native insect species) for five years across six sites. We used generalized linear mixed models to assess the impact of herbivory and weather on plant relative growth rate (RGR) and sexual reproduction, and we used Fisher's exact test to estimate the impact of herbivory on survival. Weather variables (precipitation and temperature) were consistently significant predictors of vital rate variation for both cactus species, in contrast to the limited and varied impacts of insect herbivory. Weather only significantly influenced the impact of herbivory on Opuntia humifusa fruit production. The relationships of RGR and fruit production with precipitation suggest that precipitation serves as a cue in determining the trade‐off in the allocation of resources to growth or fruit production. The presence of the native bug explained vital rate variation for both cactus species, whereas the invasive moth explained variation only for O. stricta. Despite the inconsistent effect of herbivory across vital rates and cactus species, almost half of O. stricta plants declined in size, and the invasive insect negatively affected RGR and fruit production. Given that fruit production was strongly size‐dependent, this suggests that O. stricta populations at the locations surveyed are transitioning to a size distribution of predominantly smaller sizes and with reduced sexual reproduction potential.
Discriminating patterns and drivers of multiscale movement in herpetofauna: The dynamic and changing environment of the Mojave desert tortoise
Authors: Sadoti Giancarlo , Gray Miranda E. , Farnsworth Matthew L. , Dickson Brett G.
Published: July 2017

Changes to animal movement in response to human‐induced changes to the environment are of growing concern in conservation. Most research on this problem has focused on terrestrial endotherms, but changes to herpetofaunal movement are also of concern given their limited dispersal abilities and specialized thermophysiological requirements. Animals in the desert region of the southwestern United States are faced with environmental alterations driven by development (e.g., solar energy facilities) and climate change. Here, we study the movement ecology of a desert species of conservation concern, the Mojave desert tortoise (Gopherus agassizii). We collected weekly encounter locations of marked desert tortoises during the active (nonhibernation) seasons in 2013–2015, and used those data to discriminate movements among activity centers from those within them. We then modeled the probability of movement among activity centers using a suite of covariates describing characteristics of tortoises, natural and anthropogenic landscape features, vegetation, and weather. Multimodel inference indicated greatest support for a model that included individual tortoise characteristics, landscape features, and weather. After controlling for season, date, age, and sex, we found that desert tortoises were more likely to move among activity centers when they were further from minor roads and in the vicinity of barrier fencing; we also found that movement between activity centers was more common during periods of greater rainfall and during periods where cooler temperatures coincided with lower rainfall. Our findings indicate that landscape alterations and climate change both have the potential to impact movements by desert tortoises during the active season. This study provides an important baseline against which we can detect future changes in tortoise movement behavior.
Assessing the effects of iron enrichment across holobiont compartments reveals reduced microbial nitrogen fixation in the Red Sea coral Pocillopora verrucosa
Authors: Rädecker Nils , Pogoreutz Claudia , Ziegler Maren , Ashok Ananya , Barreto Marcelle M. , Chaidez Veronica , Grupstra Carsten G. B. , Ng Yi Mei , Perna Gabriela , Aranda Manuel , Voolstra Christian R.
Published: July 2017

The productivity of coral reefs in oligotrophic tropical waters is sustained by an efficient uptake and recycling of nutrients. In reef‐building corals, the engineers of these ecosystems, this nutrient recycling is facilitated by a constant exchange of nutrients between the animal host and endosymbiotic photosynthetic dinoflagellates (zooxanthellae), bacteria, and other microbes. Due to the complex interactions in this so‐called coral holobiont, it has proven difficult to understand the environmental limitations of productivity in corals. Among others, the micronutrient iron has been proposed to limit primary productivity due to its essential role in photosynthesis and bacterial processes. Here, we tested the effect of iron enrichment on the physiology of the coral Pocillopora verrucosa from the central Red Sea during a 12‐day experiment. Contrary to previous reports, we did not see an increase in zooxanthellae population density or gross photosynthesis. Conversely, respiration rates were significantly increased, and microbial nitrogen fixation was significantly decreased. Taken together, our data suggest that iron is not a limiting factor of primary productivity in Red Sea corals. Rather, increased metabolic demands in response to iron enrichment, as evidenced by increased respiration rates, may reduce carbon (i.e., energy) availability in the coral holobiont, resulting in reduced microbial nitrogen fixation. This decrease in nitrogen supply in turn may exacerbate the limitation of other nutrients, creating a negative feedback loop. Thereby, our results highlight that the effects of iron enrichment appear to be strongly dependent on local environmental conditions and ultimately may depend on the availability of other nutrients.
Testing the validity of telephone interviews to assess chronic pain in children and adolescents: A randomized cross‐over trial
Authors: Wager J. , Barth F. , Stahlschmidt L. , Zernikow B.
Published: July 2017

Background

Telephone surveys are intended to reduce attrition in longitudinal studies. For paediatric chronic pain patients, the comparability of pain‐related information gathered using telephone interviews and postal surveys remain unknown. Furthermore, it remains unknown how social desirability may influence answers.

Methods

To compare data from telephone interviews and postal surveys, a randomized cross‐over design with two measure points 2 weeks apart and four conditions (combinations of telephone interviews (T) and postal surveys (P): P‐T, T‐P, P‐P, T‐T) was conducted in a sample of N = 323 paediatric chronic pain patients.

Results

In the inter‐group comparison, pain‐related information did not differ between telephone interviews and postal surveys except for the information on pain location (back and extremities). Agreement measures of the intra‐group comparisons suggest substantial to excellent agreements for all items and did not differ between the groups. The internal consistency of a disability scale was excellent for both assessment modes; the number of missing values did not differ. Participation rate was higher for telephone interviews compared to the postal surveys. Across both time points, attrition was lowest for the groups without a switch in assessment mode compared to the groups with a switch in assessment mode. Except for pain‐related school absence, no effect of social desirability occurred.

Conclusions

Telephone interviews are a useful method to achieve a high response rate. Pain locations should be asked for separately and not in an open question when interviewing children and adolescents on the telephone.

Significance

Telephone interviews are a good method to achieve a high response rate and obtain valid data in studies with paediatric chronic pain patients.
A simple method to estimate the isoelectric point of modified Tomato bushy stunt virus (TBSV) particles
Authors: Braun Mario , Gebauer Wolfgang , Krczal Gabriela , Ziegler Christiane , Müller‐Renno Christine , Boonrod Kajohn
Published: July 2017

We present a simple method to estimate the isoelectric point (pI) of Tomato Bushy Stunt particles. We demonstrate that the combination of agarose gels with different pH buffers can be used to electrophorese the virus particles and their migration patterns can be compared. This method allows us to estimate the pIof the virus particles (wild type, wt, and genetically modified particles) and to monitor the effect of the pIof modified peptide side chains of the viral capsid subunit on the pIof the whole virus particle.