bluuebunny/crossref_metadata_2025 huggingface dataset:
Static and Dynamic Permittivity Measurement of High Explosives in the W Band to Investigate Shock and Detonation Phenomena
Authors: Rougier Benoit , Lefrançois Alexandre , Chuzeville Vincent , Poeuf Sandra , Aubert Hervé
Published: November 2018

Radio interferometry techniques are often used to investigate shock and detonation phenomena thanks to the radio‐transparency of high explosives in the gigahertz frequency band. These techniques require the knowledge of the permittivity of studied explosives. Although the permittivity has been thoroughly studied for many materials, very few data are available at high frequencies (>75 GHz) for high explosives. In this paper, we report static measurement data of the permittivity for various reactive materials using the standard line transmission method between 75 GHz and 110 GHz (W frequency Band), and we present dynamic measurement results at 94 GHz obtained from the so‐called detonation wavefront tracking method. It is shown that the measurement results provided by these two methods are in good agreement. As a consequence, this work validates the detonation wavefront tracking method for the dynamic measurement of high explosives permittivity, and shows that the static experimental results are relevant for shock wave propagation analysis from millimeter‐wave measurement techniques.
Utility of Glycosylated TIMP3 molecules: Inhibition of MMPs and TACE to improve cardiac function in rat myocardial infarct model
Authors: Chintalgattu Vishnu , Greenberg Joanne , Singh Shivani , Chiueh Venice , Gilbert Amy , O'Neill Jason W. , Smith Stephen , Jackson Simon , Khakoo Aarif Y. , Lee TaeWeon
Published: November 2018

Tissue Inhibitor of Metalloproteinase 3 (TIMP3) is a secreted protein that has a great utility to inhibit elevated metalloproteinase (MMP) activity in injured tissues including infarcted cardiac tissue, inflamed vessels, and joint cartilages. An imbalance between TIMP3 and active MMP levels in the local tissue area may cause worsening of disease progression. To counter balance elevated MMP levels, exogenous administration of TIMP3 appeared to be beneficial in preclinical studies. However, the current form of WT‐TIMP3 molecule has a limitation to be a therapeutic candidate due to low production yield, short plasma half‐life, injection site retention, and difficulty in delivery, etc. We have engineered TIMP3 molecules by adding extra glycosylation sites or fusing with albumin, Fc, and antibody to improve pharmacokinetic properties. In general, the C‐terminal fusion of TIMP3 improved expression and production in mammalian cells and extended half‐lives dramatically 5‐20 folds. Of note, a site‐specific glycosylation at K22S/F34N resulted in a higher level of expression and better cardiac function compared to other fusion proteins in the context of left ventricle ejection fraction (LVEF) changes in a rat myocardial infarction model. It appeared that cardiac efficacy depends on a high ECM binding affinity, in which K22S/F34N and N‐TIMP3 showed a higher binding to the ECM compared to other engineered molecules. In conclusion, we found that the ECM binding and sustained residence of injected TIMP3 molecules are important for cardiac tissue localization and inhibition of adverse remodeling activity.
Speeding up the ensemble data assimilation system of the limited‐area model of Météo‐France using a block Krylov algorithm
Authors: Mercier François , Michel Yann , Montmerle Thibaut , Jolivet Pierre , Gürol Selime
Published: November 2018

Ensembles of data assimilations (EDA) in numerical weather prediction (NWP) are frequently used for both initialization of ensemble prediction systems and provision of background‐error statistics to a deterministic variational data assimilation scheme. The EDA consists of running multiple data assimilation schemes in parallel with perturbed observations and backgrounds. This kind of ensemble is computationally expensive, in particular because it requires the solution of as many linear systems as there are members in the ensemble.

Recently, we proposed the use of block Krylov methods to take advantage of the EDA structure to solve all the linear systems simultaneously, allowing us to reduce the number of iterations needed for convergence. This approach is studied further in this article. We develop advanced parallelization strategies for the block Krylov method formulated in observation space using the Object‐Oriented Prediction System (OOPS) jointly developed by the European Centre for Medium‐Range Weather Forecasts, Météo‐France, and their partners.

The algorithm is fully tested with the EDA of the limited‐area model AROME of Météo‐France, for different weather situations and configurations representative of the current system, namely assimilating around 104–105 observations together with 25 members. This new block Krylov approach allows us to gain from 13–45% of the computational time of the minimizations. Experiments with extended configurations that assimilate more observations and use more ensemble members confirm the potential of the algorithm in the future, with gains of up to 65%.
Ensemble singular vectors as additive inflation in the Local Ensemble Transform Kalman Filter (LETKF) framework with a global NWP model
Authors: Shin Seoleun , Kang Ji‐Sun , Yang Shu‐Chih , Kalnay Eugenia
Published: November 2018

We test an ensemble data assimilation system using the four‐dimensional Local Ensemble Transform Kalman Filter (4D‐LETKF) for a global numerical weather prediction (NWP) model with unstructured grids on the cubed‐sphere. It is challenging to selectively represent structures of dynamically growing errors in background states under system uncertainties such as sampling and model errors. We compute Ensemble Singular Vectors (ESVs) in an attempt to capture fast‐growing errors on the subspace spanned by ensemble perturbations, and use them as additive inflation to enlarge the covariance in the area where errors are flow‐dependently growing. The performance of the 4D‐LETKF system with ESVs is evaluated in real data assimilation, as well as Observing System Simulation Experiments (OSSEs). We find that leading ESVs help to capture fast‐growing errors effectively, especially when model errors are present, and that the use of ESVs as additive inflation significantly improves the performance of the 4D‐LETKF.
Distributed leader‐follower consensus for a class of semilinear second‐order multiagent systems using time scale theory
Authors: Babenko Serhii , Defoort Michael , Djemai Mohamed , Nicaise Serge
Published: November 2018

The problem of distributed leader‐follower consensus for second‐order linear multiagent systems with unknown nonlinear inherent dynamics is investigated in this paper. It is assumed that the dynamic of each agent is described by a semilinear second‐order dynamic equation on an arbitrary time scale. Using calculus on time scales and direct Lyapunov's method, some sufficient conditions are derived to ensure that the tracking errors exponentially converge to zero. Some numerical results show the effectiveness of the proposed scheme.
Random Čech complexes on Riemannian manifolds
Authors: Bobrowski Omer , Oliveira Goncalo
Published: November 2018

In this paper we study the homology of a random Čech complex generated by a homogeneous Poisson process in a compact Riemannian manifold M. In particular, we focus on the phase transition for “homological connectivity” where the homology of the complex becomes isomorphic to that of M. The results presented in this paper are an important generalization of , from the flat torus to general compact Riemannian manifolds. In addition to proving the statements related to homological connectivity, the methods we develop in this paper can be used as a framework for translating results for random geometric graphs and complexes from the Euclidean setting into the more general Riemannian one.
Serum from Asthmatic Mice Potentiates the Therapeutic Effects of Mesenchymal Stromal Cells in Experimental Allergic Asthma
Authors: Abreu Soraia C. , Xisto Debora G. , Oliveira Tainá B. , Blanco Natalia G. , Castro Lígia Lins , Kitoko Jamil Zola , Olsen Priscilla C. , Lopes-Pacheco Miquéias , Morales Marcelo M. , Weiss Daniel J. , Rocco Patricia R.M.
Published: November 2018

Asthma is a chronic inflammatory disease characterized by airway inflammation and remodeling, which can lead to progressive decline of lung function. Although mesenchymal stromal cells (MSCs) have shown beneficial immunomodulatory properties in preclinical models of allergic asthma, effects on airway remodeling have been limited. Mounting evidence suggests that prior exposure of MSCs to specific inflammatory stimuli or environments can enhance their immunomodulatory properties. Therefore, we investigated whether stimulating MSCs with bronchoalveolar lavage fluid (BALF) or serum from asthmatic mice could potentiate their therapeutic properties in experimental asthma. In a house dust mite (HDM) extract asthma model in mice, unstimulated, asthmatic BALF-stimulated, or asthmatic serum-stimulated MSCs were administered intratracheally 24 hours after the final HDM challenge. Lung mechanics and histology; BALF protein, cellularity, and biomarker levels; and lymph-node and bone marrow cellularity were assessed. Compared with unstimulated or BALF-stimulated MSCs, serum-stimulated MSCs further reduced BALF levels of interleukin (IL)-4, IL-13, and eotaxin, total and differential cellularity in BALF, bone marrow and lymph nodes, and collagen fiber content, while increasing BALF IL-10 levels and improving lung function. Serum stimulation led to higher MSC apoptosis, expression of various mediators (transforming growth factor-β, interferon-γ, IL-10, tumor necrosis factor-α-stimulated gene 6 protein, indoleamine 2,3-dioxygenase-1, and IL-1 receptor antagonist), and polarization of macrophages to M2 phenotype. In conclusion, asthmatic serum may be a novel strategy to potentiate therapeutic effects of MSCs in experimental asthma, leading to further reductions in both inflammation and remodeling than can be achieved with unstimulated MSCs. Stem Cells Translational Medicine  2019;8:301&312
Chemical Degradation of Poly(bisphenol A carbonate) Waste Materials: A Review
Authors: Singh Ram , Shahi Surybala , Geetanjali
Published: November 2018

Plastics are indispensable and integral part of our daily life. Each year, we generate tonnes of plastics waste. Poly(bisphenol A carbonate) has created a space for itself in the plastic industry due to its high performance properties. The high rate of production created a major challenge in its management after use or becoming as waste. In this brief review, we have described the chemical degradation of poly(bisphenol A carbonate) and the use of catalyst and reagents. Some of the most utilized chemical degradation methods like alcoholysis, hydrolysis and aminolysis have been explained in detail. The chemical reactions involved in the degradation process have also been discussed.
Phosphine‐Catalyzed [3 + 2] Annulation of γ‐ Substituted Allenoates: Novel Access to Functionalized Cyclopentenes and Bicyclic[3, 3, 0]octene Derivatives
Authors: Li Erqing , Jin Hongxing , Huang You
Published: November 2018

The phosphine‐catalyzed [3 + 2] cyclizations of γ‐substituted allenoates have been applied to the synthesis of functionalized cyclopentenes and bicyclic compounds in moderate to good yields. The operation is simple and scalable with good functional group tolerance. In addition, the novel substrate‐controlled phosphine‐catalyzed domino reaction not only enriches the chemistry of γ‐substituted allenoates, but also enables easy access to skeletally diverse products.
Control of Shell Morphology in p–n Heterostructured Water‐Processable Semiconductor Colloids: Toward Extremely Efficient Charge Separation
Authors: Kim Yu Jin , Schaller Richard D. , Fry Harry Christopher
Published: November 2018

This article describes p–n heterostructured water‐borne semiconductor naonoparticles (NPs) with unique surface structures via control of shell morphology. The shell particles, comprising PC60–[6,6]‐phenyl‐C61‐butyric acid methyl ester (PC61BM) composite, having n‐type semiconductor characteristics, notably influence the charge carrier behavior in the core–shell NPs. A one‐ or two‐phase methodology based on a PC60 surfactant‐water phase and PC61BM n‐type semiconductor‐organic phase provides highly specific control over the shell structure of the NPs, which promote their superior charge separation ability when combined with poly‐3‐hexyl‐thiophene (P3HT). Moreover, the resulting water‐borne NP exhibits shell morphology‐dependent carrier quenching and stability, which is characterized via luminescence studies paired with structural analysis. Corresponding to the results, outstanding performances of photovoltaic cells with over 5% efficiency are achieved. The results suggest that the surrounding shell environments, such as the shell structure, and its electronic charge density, are crucial in determining the overall activity of the core–shell p–n heterostructured NPs. Thus, this work provides a new protocol in the current fields of water‐based organic semiconductor colloids.
Applying Asymmetric, Case-Based, Forecasting Modeling in Service Research: Cultures’ Consequences on Customers’ Service Gratuities
Authors: Ferguson Graham , Megehee Carol M. , Woodside Arch G.
Published: November 2018

This study provides a theory of the influences of alternative national cultures (as complex wholes) on customers’ tipping behaviors following receiving of services in restaurants and taxis. Based on complexity theory tenets, the study constructs and tests models asymmetrically—offers separate models for explaining and forecasting high tipping versus low tipping national cultures. The study uses multiple sources of secondary data for 30 nations including Hofstede's first four culture values, religiosity, Gini index, and GDP_PPP. Model construction includes computing-with-words (CWW) screens that prior theory forecasts to be accurate in identifying high (low) tipping behavior. Analysis includes using fuzzy-set qualitative comparative analysis (fsQCA) and somewhat precise outcome testing (SPOT) of the consistency (degree of accuracy) and coverage for each model. Model testing includes predictive as well as fit validation. The findings support core tenets of complexity theory (e.g., equifinality of different recipes for the same outcome, both negative and positive associations of individual ingredients in different recipes contribute to the same outcome, and causal asymmetry). Because national cultures are complex wholes, hospitality researchers need to embrace the complexity theory tenets and asymmetric tools to achieve deep understanding and for accurately forecasting of customer responses to hospitality services. This study provides new theory and methodological tools for recognizing the complexities and forecasting customers’ behavior in their responses following receiving hospitality services.
THE BED CANOPY IN XENOPHON OF EPHESUS AND THE ICONOGRAPHY OF MARS AND VENUS UNDER THE EMPIRE
Authors: Lefteratou Anna
Published: November 2018

This paper discusses how Roman visual culture might be useful for deciphering the ecphrastic passages of the ancient Greek novel. Whereasecphrasishas been one of the blossoming topics in the field, the examination of novelisticecphrasisalongside particular works of art is still a desideratum. As a test case I will use Xenophon of Ephesus’ecphrasisof the bed canopy depicting Ares’ and Aphrodite's embrace, in theEphesiaca,a novel that might have been written as early as AD 65. In what follows I will argue that the scene described on the canopy would have stimulated a variety of intertexts, both literary and visual, in the minds of the imperial audience: that is, Xenophon's reader would have been encouraged to recall not just Demodocus’ song of the love of Ares and Aphrodite but also the idealised Roman version of the myth, which was so frequently depicted on frescoes and mosaics in Roman villas in the first century. I then explore Xenophon's ‘interpretatio Romana’through the adaptations of the Ares and Aphrodite myth found in Plutarch and Lucian.
A NOTE ON THE IMPACT OF NEWS ON US HOUSEHOLD INFLATION EXPECTATIONS
Authors: Wang Ben Zhe , Sheen Jeffrey , Trück Stefan , Chao Shih-Kang , Härdle Wolfgang Karl
Published: November 2018

Monthly disaggregated US data from 1978 to 2016 reveal that exposure to news on inflation and monetary policy helps to explain inflation expectations. This remains true when controlling for household personal characteristics, perceptions of government policy effectiveness, expectations of future interest and unemployment rates, and sentiment. We find an asymmetric impact of news on inflation and monetary policy after 1983, with news on rising inflation and easier monetary policy having a stronger effect in comparison to news on lowering inflation and tightening monetary policy. Our results indicate the impact on inflation expectations of monetary policy news manifested through consumer sentiment during the lower bound period.
INTERNATIONAL HOUSING MARKETS, UNCONVENTIONAL MONETARY POLICY, AND THE ZERO LOWER BOUND
Authors: Huber Florian , Punzi Maria Teresa
Published: November 2018

In this paper, we analyze the relationship between unconventional monetary policy (UMP), measured through shadow interest rates, and housing markets for the USA, the United Kingdom, Japan, and the Euro Area using a set of time-varying parameter vector autoregressive models. Our findings suggest that the monetary policy transmission mechanism to the housing market has not changed with the implementation of quantitative easing or forward guidance for most economies considered. A counterfactual exercise provides some evidence that UMP has been particularly successful in dampening the consequences of the financial crisis on housing markets in the USA, while the effects are more muted in the remaining countries considered.
PRECAUTIONARY LEARNING AND INFLATIONARY BIASES
Authors: Dave Chetan , Feigenbaum James
Published: November 2018

In a canonical monetary policy model in which the central bank learns about underlying fundamentals by estimating the parameters of a Phillips curve, we show that the bank’s loss function is asymmetric such that parameter overestimates may be more or less costly than underestimates, creating a precautionary motive in estimation. This motive suggests the use of a more efficient variance-adjusted least-squares estimator for learning about fundamentals. Informed by this “precautionary learning” the central bank sets low inflation targets, and the economy can settle near a Ramsey equilibrium.
Double bind at the UN: Western actors, Russia, and the traditionalist agenda
Authors: STOECKL KRISTINA , MEDVEDEVA KSENIYA
Published: November 2018

This article is dedicated to analysis of the traditionalist agenda, promoted by Russia, in recent debates in the United Nations Human Rights Council (‘Traditional values’ from 2009 to 2013, ‘Protection of the family’ from 2014 to 2017). The traditionalist agenda could be interpreted as yet another chapter of contextualist opposition to the universalist application human of rights and as a successor to the cultural relativism in human rights promoted in the past by the Organization of Islamic States or countries from the Global South. This article seeks to challenge such an interpretation and instead makes the argument that the traditionalist agenda employs novel aspects of illiberal norm protagonism in the human rights sphere. The article undertakes an in-depth analysis of the discourse coalitions of both supporters and opponents of the traditionalist agenda, using the tools of discourse analysis in international relations and drawing on a constructivist approach to norm diffusion in international organisations.
Mao Receives 2018 Mineral and Rock Physics Early Career Award
Authors:   AGU
Published: November 2018

Zhu Mao will receive the 2018 Mineral and Rock Physics Early Career Award at AGU’s Fall Meeting 2018, to be held 10–14 December in Washington, D. C. The award is given to early-career scientists “in recognition of outstanding contributions in the broadly defined area of mineral and rock physics.”
Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD+
Authors: Iannetti Eligio F. , Smeitink Jan A. M. , Willems Peter H. G. M. , Beyrath Julien , Koopman Werner J. H.
Published: November 2018

Cell models of mitochondrial complex I (CI) deficiency display activation of glycolysis to compensate for the loss in mitochondrial ATP production. This adaptation can mask other relevant deficiency-induced aberrations in cell physiology. Here we investigated the viability, mitochondrial morphofunction, ROS levels and ATP homeostasis of primary skin fibroblasts from Leigh Syndrome (LS) patients with isolated CI deficiency. These cell lines harbored mutations in nuclear DNA (nDNA)-encoded CI genes (NDUFS7, NDUFS8, NDUFV1) and, to prevent glycolysis upregulation, were cultured in a pyruvate-free medium in which glucose was replaced by galactose. Following optimization of the cell culture protocol, LS fibroblasts died in the galactose medium, whereas control cells did not. LS cell death was dose-dependently inhibited by pyruvate, malate, oxaloacetate, α-ketoglutarate, aspartate, and exogenous NAD+ (eNAD), but not by lactate, succinate, α-ketobutyrate, and uridine. Pyruvate and eNAD increased the cellular NAD+ content in galactose-treated LS cells to a different extent and co-incubation studies revealed that pyruvate-induced rescue was not primarily mediated by NAD+. Functionally, in LS cells glucose-by-galactose replacement increased mitochondrial fragmentation and mass, depolarized the mitochondrial membrane potential (Δψ), increased H2DCFDA-oxidizing ROS levels, increased mitochondrial ATP generation, and reduced the total cellular ATP content. These aberrations were differentially rescued by pyruvate and eNAD, supporting the conclusion that these compounds rescue galactose-induced LS cell death via different mechanisms. These findings establish a cell-based strategy for intervention testing and enhance our understanding of CI deficiency pathophysiology.
Customizing supercontinuum generation via on-chip adaptive temporal pulse-splitting
Authors: Wetzel Benjamin , Kues Michael , Roztocki Piotr , Reimer Christian , Godin Pierre-Luc , Rowley Maxwell , Little Brent E. , Chu Sai T. , Viktorov Evgeny A. , Moss David J. , Pasquazi Alessia , Peccianti Marco , Morandotti Roberto
Published: November 2018

Modern optical systems increasingly rely on complex physical processes that require accessible control to meet target performance characteristics. In particular, advanced light sources, sought for, for example, imaging and metrology, are based on nonlinear optical dynamics whose output properties must often finely match application requirements. However, in these systems, the availability of control parameters (e.g., the optical field shape, as well as propagation medium properties) and the means to adjust them in a versatile manner are usually limited. Moreover, numerically finding the optimal parameter set for such complex dynamics is typically computationally intractable. Here, we use an actively controlled photonic chip to prepare and manipulate patterns of femtosecond optical pulses that give access to an enhanced parameter space in the framework of supercontinuum generation. Taking advantage of machine learning concepts, we exploit this tunable access and experimentally demonstrate the customization of nonlinear interactions for tailoring supercontinuum properties.
Using single nucleotide variations in single-cell RNA-seq to identify subpopulations and genotype-phenotype linkage
Authors: Poirion Olivier , Zhu Xun , Ching Travers , Garmire Lana X.
Published: November 2018

Despite its popularity, characterization of subpopulations with transcript abundance is subject to a significant amount of noise. We propose to use effective and expressed nucleotide variations (eeSNVs) from scRNA-seq as alternative features for tumor subpopulation identification. We develop a linear modeling framework, SSrGE, to link eeSNVs associated with gene expression. In all the datasets tested, eeSNVs achieve better accuracies than gene expression for identifying subpopulations. Previously validated cancer-relevant genes are also highly ranked, confirming the significance of the method. Moreover, SSrGE is capable of analyzing coupled DNA-seq and RNA-seq data from the same single cells, demonstrating its value in integrating multi-omics single cell techniques. In summary, SNV features from scRNA-seq data have merits for both subpopulation identification and linkage of genotype-phenotype relationship.
BAFopathies’ DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin–Siris and Nicolaides–Baraitser syndromes
Authors: Aref-Eshghi Erfan , Bend Eric G. , Hood Rebecca L. , Schenkel Laila C. , Carere Deanna Alexis , Chakrabarti Rana , Nagamani Sandesh C. S. , Cheung Sau Wai , Campeau Philippe M. , Prasad Chitra , Siu Victoria Mok , Brady Lauren , Tarnopolsky Mark A. , Callen David J. , Innes A. Micheil , White Susan M. , Meschino Wendy S. , Shuen Andrew Y. , Paré Guillaume , Bulman Dennis E. , Ainsworth Peter J. , Lin Hanxin , Rodenhiser David I. , Hennekam Raoul C. , Boycott Kym M. , Schwartz Charles E. , Sadikovic Bekim
Published: November 2018

Coffin–Siris and Nicolaides–Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B,SMARCB1, andSMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboringARID1Bdeletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening.
A third generation of radical fluorinating agents based on N-fluoro-N-arylsulfonamides
Authors: Meyer Daniel , Jangra Harish , Walther Fabian , Zipse Hendrik , Renaud Philippe
Published: November 2018

Radical fluorination has been known for a long time, but synthetic applications were severely limited by the hazardous nature of the first generation of reagents such as F2 and the strongly electrophilic nature of the second generation of reagents such as N-fluorobenzenesulfonimide (NFSI) and Selecfluor®. Here, we report the preparation, use and properties of N-fluoro-N-arylsulfonamides (NFASs), a class of fluorinating reagents suitable for radical fluorination under mild conditions. Their N–F bond dissociation energies (BDE) are 30–45 kJ mol−1 lower than the N–F BDE of the reagents of the second generation. This favors clean radical fluorination processes over undesired side reactions. The utility of NFASs is demonstrated by a metal-free radical hydrofluorination of alkenes including an efficient remote C–H fluorination via a 1,5-hydrogen atom transfer. NFASs have the potential to become the reagents of choice in many radical fluorination processes.
Retroactive and graded prioritization of memory by reward
Authors: Braun Erin Kendall , Wimmer G. Elliott , Shohamy Daphna
Published: November 2018

Many decisions are based on an internal model of the world. Yet, how such a model is constructed from experience and represented in memory remains unknown. We test the hypothesis that reward shapes memory for sequences of events by retroactively prioritizing memory for objects as a function of their distance from reward. Human participants encountered neutral objects while exploring a series of mazes for reward. Across six data sets, we find that reward systematically modulates memory for neutral objects, retroactively prioritizing memory for objects closest to the reward. This effect of reward on memory emerges only after a 24-hour delay and is stronger for mazes followed by a longer rest interval, suggesting a role for post-reward replay and overnight consolidation, as predicted by neurobiological data in animals. These findings demonstrate that reward retroactively prioritizes memory along a sequential gradient, consistent with the role of memory in supporting adaptive decision-making.
Bimodal sensing of guidance cues in mechanically distinct microenvironments
Authors: Tabdanov Erdem D. , Puram Vikram V. , Win Zaw , Alamgir Ashab , Alford Patrick W. , Provenzano Paolo P.
Published: November 2018

Contact guidance due to extracellular matrix architecture is a key regulator of carcinoma invasion and metastasis, yet our understanding of how cells sense guidance cues is limited. Here, using a platform with variable stiffness that facilitates uniaxial or biaxial matrix cues, or competing E-cadherin adhesions, we demonstrate distinct mechanoresponsive behavior. Through disruption of traction forces, we observe a profound phenotypic shift towards a mode of dendritic protrusion and identify bimodal processes that govern guidance sensing. In contractile cells, guidance sensing is strongly dependent on formins and FAK signaling and can be perturbed by disrupting microtubule dynamics, while low traction conditions initiate fluidic-like dendritic protrusions that are dependent on Arp2/3. Concomitant disruption of these bimodal mechanisms completely abrogates the contact guidance response. Thus, guidance sensing in carcinoma cells depends on both environment architecture and mechanical properties and targeting the bimodal responses may provide a rational strategy for disrupting metastatic behavior.
Autapses enhance bursting and coincidence detection in neocortical pyramidal cells
Authors: Yin Luping , Zheng Rui , Ke Wei , He Quansheng , Zhang Yi , Li Junlong , Wang Bo , Mi Zhen , Long Yue-sheng , Rasch Malte J. , Li Tianfu , Luan Guoming , Shu Yousheng
Published: November 2018

Autapses are synaptic contacts of a neuron’s axon onto its own dendrite and soma. In the neocortex, self-inhibiting autapses in GABAergic interneurons are abundant in number and play critical roles in regulating spike precision and network activity. Here we examine whether the principal glutamatergic pyramidal cells (PCs) also form functional autapses. In patch-clamp recording from both rodent and human PCs, we isolated autaptic responses and found that these occur predominantly in layer-5 PCs projecting to subcortical regions, with very few in those projecting to contralateral prefrontal cortex and layer 2/3 PCs. Moreover, PC autapses persist during development into adulthood. Surprisingly, they produce giant postsynaptic responses (∼5 fold greater than recurrent PC-PC synapses) that are exclusively mediated by AMPA receptors. Upon activation, autapses enhance burst firing, neuronal responsiveness and coincidence detection of synaptic inputs. These findings indicate that PC autapses are functional and represent an important circuit element in the neocortex.
Crossover from positive to negative optical torque in mesoscale optical matter
Authors: Han Fei , Parker John A. , Yifat Yuval , Peterson Curtis , Gray Stephen K. , Scherer Norbert F. , Yan Zijie
Published: November 2018

The photons in circularly polarized light can transfer their quantized spin angular momentum to micro- and nanostructures via absorption and scattering. This normally exerts positive torque on the objects wher the sign (i.e., handedness or angular direction) follows that of the spin angular momentum. Here we show that the sign of the optical torque can be negative in mesoscopic optical matter arrays of metal nanoparticles (NPs) assembled in circularly polarized optical traps. Crossover from positive to negative optical torque, which occurs for arrays with different number, separation and configuration of the constituent particles, is shown to result from many-body interactions as clarified by electrodynamics simulations. Our results establish that both positive and negative optical torque can be readily realized and controlled in optical matter arrays. This property and reconfigurability of the arrays makes possible programmable materials for optomechanical, microrheological and biological applications.
Tailoring atomic layer growth at the liquid-metal interface
Authors: Cao Hai , Waghray Deepali , Knoppe Stefan , Dehaen Wim , Verbiest Thierry , De Feyter Steven
Published: November 2018

Engineering atomic structures at metal surfaces represents an important step in the development of novel nanomaterials and nanodevices, but relies predominantly on atomic/molecular beam epitaxy under ultrahigh vacuum conditions, where controlling the deposition processes remains challenging. By using solution-borne nanosized gold clusters as a precursor, here we develop a wet deposition protocol to the fabrication of atomically flat gold nanoislands, so as to utilize the dynamic exchange of surface-active molecules at the liquid-metal interface for manipulating the growth kinetics of ultrathin metallic nanostructures. While remarkable shape and size selection of gold nanoislands is observed, our experimental and theoretical investigations provide compelling evidences that organic adsorbates can impart a bias to the island orientation by preferred adsorption and alignment and intervene in the assembly and disassembly of adatom islands by complexing with Au adatoms. This approach offers a simple solution to regulate atomic layer growth of metals at ambient conditions.
24-hour levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson’s disease
Authors: Cruse Belinda , Morales-Briceño Hugo , Chang Florence C F , Mahant Neil , Ha Ainhi D , Kim Samuel D , Wolfe Nigel , Kwan Vu , Tsui David S , Griffith Jane M , Galea Donna , Fung Victor S C
Published: November 2018

Levodopa-carbidopa intestinal gel (LCIG) is effective for the control of motor fluctuations in Parkinson’s disease (PD). The objective of this study is to report the reduction of dyskinesias after transitioning from 16 to 24-h/day LCIG infusion. From a cohort of 74 PD patients treated with LCIG for motor fluctuations, we identified 12 patients that were treated with 24-h per day infusion with the aim to control troublesome daytime dyskinesia. Clinical, demographic, dyskinesia rating scales were evaluated. Daytime dyskinesia was reduced in 75% (9/12) patients following treatment with 24-h therapy, including 7 who were compared with 16-h therapy and 2 that were transitioned from oral dopaminergic therapy to 24-h LCIG. Combining the data from all 12 subjects, troublesome dyskinesias were reduced during 24-h LCIG; UPDRS 4.1 (time spent with dyskinesias) mean change was −1.5 ± 0.75, p = 0.010 (Wilcoxon signed-rank test) and UPDRS 4.2 (functional impact of dyskinesias) mean change was −1.7 ± 0.90, p = 0.016, without changing their UPDRS part 3 “ON” scores (p = 0.138) or H&Y (p = 0.157). In 5 patients, improvement in dyskinesia occurred despite an overall increase in the total daily levodopa dose. None of the patients had worsening of dyskinesia after a median follow-up of 28 months. 24-h per day infusion of LCIG may be a useful strategy in the management of troublesome dyskinesias in PD patients with disabling dyskinesias resistant to attempts to optimise 16-hours per day therapy. We postulate that this may be due to a pharmacodynamic as opposed to pharmacokinetic mechanism.
Extensional and shear rheology of okra polysaccharides in the presence of artificial saliva
Authors: Yuan Bo , Ritzoulis Christos , Chen Jianshe
Published: November 2018

Extensional and shear viscosities were studied for mixtures comprising artificial saliva and okra mucilage, the latter acting as a model thick-liquid food. These experiments aimed to obtain information on the flow-behavior information of the systems, underpinning the texture sensation of foods as perceived by dysphagic and xerostomic populations. Mixing okra mucilage with artificial saliva dramatically increases the shear viscosity of artificial saliva throughout the studied ranges of concentrations and deformation rates. Particle tracking does not suggest direct interactions between the components of artificial saliva and of okra mucilage. The rheology of the okra polymer (OP)–artificial saliva (AS) mixture is dominated by its extensional viscosity: Trouton ratios are in the order of tens to hundreds, while they decrease with increasing okra-mucilage concentration; this highlighs the dominance of the extensional rheology and the increasing importance of the shear mechanics with increasing okra content. The relaxation times and extensional moduli are also reported for the systems under study. Extensional and shear flows are of equal importance concerning the elastic behavior.
Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI
Authors: Ly K. Ina , Vakulenko-Lagun Bella , Emblem Kyrre E. , Ou Yangming , Da Xiao , Betensky Rebecca A. , Kalpathy-Cramer Jayashree , Duda Dan G. , Jain Rakesh K. , Chi Andrew S. , Plotkin Scott R. , Batchelor Tracy T. , Sorensen Gregory , Rosen Bruce R. , Gerstner Elizabeth R.
Published: November 2018

Functional MRI may identify critical windows of opportunity for drug delivery and distinguish between early treatment responders and non-responders. Using diffusion-weighted, dynamic contrast-enhanced, and dynamic susceptibility contrast MRI, as well as pro-angiogenic and pro-inflammatory blood markers, we prospectively studied the physiologic tumor-related changes in fourteen newly diagnosed glioblastoma patients during standard therapy. 153 MRI scans and blood collection were performed before chemoradiation (baseline), weekly during chemoradiation (week 1–6), monthly before each cycle of adjuvant temozolomide (pre-C1-C6), and after cycle 6. The apparent diffusion coefficient, volume transfer coefficient (Ktrans), and relative cerebral blood volume (rCBV) and flow (rCBF) were calculated within the tumor and edema regions and compared to baseline. Cox regression analysis was used to assess the effect of clinical variables, imaging, and blood markers on progression-free (PFS) and overall survival (OS). After controlling for additional covariates, high baseline rCBV and rCBF within the edema region were associated with worse PFS (microvessel rCBF: HR = 7.849, p = 0.044; panvessel rCBV: HR = 3.763, p = 0.032; panvessel rCBF: HR = 3.984; p = 0.049). The same applied to high week 5 and pre-C1 Ktrans within the tumor region (week 5 Ktrans: HR = 1.038, p = 0.003; pre-C1 Ktrans: HR = 1.029, p = 0.004). Elevated week 6 VEGF levels were associated with worse OS (HR = 1.034; p = 0.004). Our findings suggest a role for rCBV and rCBF at baseline and Ktrans and VEGF levels during treatment as markers of response. Functional imaging changes can differ substantially between tumor and edema regions, highlighting the variable biologic and vascular state of tumor microenvironment during therapy.
Enhanced fluorescent intensity of magnetic-fluorescent bifunctional PLGA microspheres based on Janus electrospraying for bioapplication
Authors: Li Kun , Li Ping , Jia Zhengtai , Qi Bing , Xu Junwei , Kang Danyue , Liu Meili , Fan Yubo
Published: November 2018

Microspheres with magnetic-fluorescent functions have received attention due to fluorescent tracking and target positioning. To improve the accuracy of optical imaging and the fluorescent tracking of drug release, it is essential to enhance the fluorescent intensity of microparticles. Magnetic-fluorescent bifunctional poly lactic-co-glycolic acid (PLGA) Janus microspheres [PLGA/TbLa3(Bim)12]//[PLGA/Fe3O4] with double chambers were fabricated with the double-needle electrospraying method. The fluorescent drug TbLa3(Bim)12 with dual rare earth ions was encapsulated in one chamber, while Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) were simultaneously encapsulated in another chamber. In comparison, magnetic-fluorescent PLGA composite microspheres PLGA/TbLa3(Bim)12/Fe3O4 were also prepared, which encapsulated fluorescent drugs TbLa3(Bim)12 with dual rare earth (RE) ions and Fe3O4 MNPs in one chamber. The fluorescent intensity at 542 nm of Janus microspheres was about three times higher than that of composite microspheres due to a decrease in contact between fluorescent-labeling RE drug and MNPs. The fluorescent intensities of Janus microspheres with different contents of Fe3O4 MNPs and TbLa3(Bim)12 were investigated. Furthermore, the magnetic properties, thermostability, cell toxicity and hemolytic properties of Janus microspheres were also assayed to conduct a tentative exploration of their bioapplication. The Janus microspheres provide many opportunities for application in biofields such as drug delivery.
High-throughput sequencing for the molecular diagnosis of Usher syndrome reveals 42 novel mutations and consolidates CEP250 as Usher-like disease causative
Authors: Fuster-García Carla , García-García Gema , Jaijo Teresa , Fornés Neus , Ayuso Carmen , Fernández-Burriel Miguel , Sánchez-De la Morena Ana , Aller Elena , Millán José M.
Published: November 2018

Usher syndrome is a rare disorder causing retinitis pigmentosa, together with sensorineural hearing loss. Due to the phenotypic and genetic heterogeneity of this disease, the best method to screen the causative mutations is by high-throughput sequencing. In this study, we tested a semiconductor chip based sequencing approach with 77 unrelated patients, as a molecular diagnosis routine. In addition, Multiplex Ligation-dependent Probe Amplification and microarray-based Comparative Genomic Hybridization techniques were applied to detect large rearrangements, and minigene assays were performed to confirm the mRNA processing aberrations caused by splice-site mutations. The designed panel included all the USH causative genes (MYO7A,USH1C,CDH23,PCDH15,USH1G,CIB2,USH2A,ADGRV1,WHRNandCLRN1) as well as four uncertainly associated genes (HARS,PDZD7,CEP250andC2orf71). The outcome showed an overall mutation detection ratio of 82.8% and allowed the identification of 42 novel putatively pathogenic mutations. Furthermore, we detected two novel nonsense mutations inCEP250in a patient with a disease mimicking Usher syndrome that associates visual impairment due to cone-rod dystrophy and progressive hearing loss. Therefore, this approach proved reliable results for the molecular diagnosis of the disease and also allowed the consolidation of theCEP250gene as disease causative for an Usher-like phenotype.
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have differential effects on cystic fibrosis macrophage function
Authors: Zhang Shuzhong , Shrestha Chandra L. , Kopp Benjamin T.
Published: November 2018

Despite the addition of cystic fibrosis transmembrane conductance regulator (CFTR) modulators to the cystic fibrosis (CF) treatment regimen, patients with CF continue to suffer from chronic bacterial infections that lead to progressive respiratory morbidity. Host immunity, and macrophage dysfunction specifically, has an integral role in the inability of patients with CF to clear bacterial infections. We sought to characterize macrophage responses to CFTR modulator treatment as we hypothesized that there would be differential effects based on patient genotype. Human CF and non-CF peripheral blood monocyte-derived macrophages (MDMs) were analyzed for CFTR expression, apoptosis, polarization, phagocytosis, bacterial killing, and cytokine production via microscopy, flow cytometry, and ELISA-based assays. Compared to non-CF MDMs, CF MDMs display decreased CFTR expression, increased apoptosis, and decreased phagocytosis. CFTR expression increased and apoptosis decreased in response to ivacaftor or lumacaftor/ivacaftor therapy, and phagocytosis improved with ivacaftor alone. Ivacaftor restored CF macrophage polarization responses to non-CF levels and reducedPseudomonas aeruginosabacterial burden, but did not reduce other bacterial loads. Macrophage inflammatory cytokine production decreased in response to ivacaftor alone. In summary, ivacaftor and lumacaftor/ivacaftor have differential impacts on macrophage function with minimal changes observed in CF patients treated with lumacaftor/ivacaftor. Overall improvements in macrophage function in ivacaftor-treated CF patients result in modestly improved macrophage-mediated bacterial killing.
Author Correction: Quantitative 3-D morphometric analysis of individual dendritic spines
Authors: Basu Subhadip , Saha Punam Kumar , Roszkowska Matylda , Magnowska Marta , Baczynska Ewa , Das Nirmal , Plewczynski Dariusz , Wlodarczyk Jakub
Published: November 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Three-dimensional (3D) morphology of Sansha Yongle Blue Hole in the South China Sea revealed by underwater remotely operated vehicle
Authors: Li Tiegang , Feng Aiping , Liu Yanxiong , Li Zhenhong , Guo Kai , Jiang Wenzheng , Du Jun , Tian Ziwen , Xu Wenxue , Liu Yang , Wang Yanru
Published: November 2018

The Sansha Yongle Blue Hole (SYBH) is the deepest blue hole found anywhere to date. Study of the SYBH can provide insight into the interactions between hole wall morphology and many geological/hydrological mechanisms. A comprehensive investigation of the SYBH was carried out for the first time in 2017 using a professional-grade underwater remotely operated vehicle (ROV) to obtain accurate depth and three-dimensional (3D) topographic data. The SYBH resembles a ballet dancer’s shoe and has a volume of ~499609 m3. The observed deepest portion of the SYBH is at 301.19 m below the local 10-year mean sea level. The cave bottom laterally deviates from its entrance by 118 m at an azimuth of 219 degrees. The cave entrance is shaped like a comma and has an average width of 130 m; the widest part is 162.3 m wide, while the narrowest part is 26.2 m wide and is at 279 mbsl (meters below sea level). The 3D topography of the SYBH and underwater photography revealed two large transitions at ~76 to 78 mbsl and at 158 mbsl, indicating that the initiation of the blue hole was likely a step wise process and that the hole wall morphology was subsequently remolded through a paleo-sea level stillstand (at or near Younger Dryas). The topographic data also indicated that the blue hole is situated within an isolated environment with no water or material exchange with the outside open sea.