bluuebunny/crossref_metadata_2025 huggingface dataset:
mTOR referees memory and disease through mRNA repression and competition
Authors: Raab‐Graham Kimberly F. , Niere Farr
Published: May 2017

Mammalian target of rapamycin (mTOR) activity is required for memory and is dysregulated in disease. Activation of mTOR promotes protein synthesis; however, new studies are demonstrating that mTOR activity also represses the translation of mRNAs. Almost three decades ago, Kandel and colleagues hypothesised that memory was due to the induction of positive regulators and removal of negative constraints. Are these negative constraints repressed mRNAs that code for proteins that block memory formation? Herein, we will discuss the mRNAs coded by putative memory suppressors, how activation/inactivation of mTOR repress protein expression at the synapse, how mTOR activity regulates RNA binding proteins, mRNA stability, and translation, and what the possible implications of mRNA repression are to memory and neurodegenerative disorders.
The effect of Doppler broadening on D region negative ion ratio measurements at Arecibo
Authors: Gong Yun , Ma Zheng , Li Yanlin , Zhou Qihou , Zhang Shaodong , Huang Chunming
Published: May 2017

We present an analysis of the ratio of negative ions to electron concentration in the D region. The analysis is based on measurements made by the Arecibo (18.3°N) incoherent scatter radar (ISR) during 10:00 LT to 17:30 LT, 4 July 2006 and 11:00 LT to 15:00 LT, 3 September 2016. Previous ISR studies inferred the negative ion ratio without considering the broadening effect that nonthermal fluctuations have on the power spectra. Our results show that the Doppler effect from high‐frequency nonthermal fluctuations plays a significant role in broadening the ISR power spectra in the lower D region. A 10 Hz power spectrum can be Doppler broadened by 50% when the vertical velocity varies continuously within ±5 m/s, which is often observed. Hence, the ratio of the negative ion to electron concentration (λ) inferred in previous ISR studies is likely overestimated. Using the measured Doppler velocities, the broadening effect on the ISR power spectra due to Doppler shift is eliminated and λ is reevaluated. The results show that λ is largest at around 69 km. Although λ stays mostly below 1, a 3 km layer with λ greater than 1 is observed in the time period of 12–13 LT, 3 September 2016. Our results are largely consistent with the model study presented by Kull et al. (1997).
Statistical properties and geoeffectiveness of southward interplanetary magnetic field with emphasis on weakly southward Bz events
Authors: Choi Kyung‐Eun , Lee Dae‐Young , Choi Kyu‐Cheol , Kim Jaehun
Published: May 2017

In this work we analyze the statistical properties and geoeffectiveness of southward interplanetary magnetic field (IMF) Bz (Bs) events measured near the Earth from 1996 to 2015. We classify the Bs events into six contrasting classes according to the duration and intensity of Bs: two subclasses of long‐lasting major intensity, two subclasses of long‐lasting weak intensity, and two subclasses of short‐lasting weak intensity. We find the following results. (1) The occurrence rate of Bs events is lowest for the long‐lasting major‐intensity Bs classes and increases toward shorter‐lasting and weaker‐intensity Bs classes. (2) Many of the Bs events in nearly all classes are associated with regions other than interplanetary coronal mass ejections and coronal hole high‐speed streams. (3) Alfvén waves account for a significant fraction of the Bs events (e.g., ~60% for the short‐lasting and weak‐intensity Bs classes). (4) There are clear differences in solar cycle dependence of Bs events among the different Bs classes. (5) Even either the long‐lasting or short‐lasting weak‐intensity class Bs events can often be geoeffective by triggering substorms of weak‐to‐medium intensity and by enhancing geosynchronous relativistic electron fluxes. In conclusion, we emphasize that even the weakly (in terms of either intensity or duration) southward IMF Bz should be considered significant from the viewpoint of their high occurrence rate and their geoeffectiveness compared to those of long‐lasting major intensity.
Exchange of carbonyl sulfide (OCS) between soils and atmosphere under various CO2 concentrations
Authors: Bunk Rüdiger , Behrendt Thomas , Yi Zhigang , Andreae Meinrat O. , Kesselmeier Jürgen
Published: May 2017

A new continuous integrated cavity output spectroscopy analyzer and an automated soil chamber system were used to investigate the exchange processes of carbonyl sulfide (OCS) between soils and the atmosphere under laboratory conditions. The exchange patterns of OCS between soils and the atmosphere were found to be highly dependent on soil moisture and ambient CO2 concentration. With increasing soil moisture, OCS exchange ranged from emission under dry conditions to an uptake within an optimum moisture range, followed again by emission at high soil moisture. Elevated CO2 was found to have a significant impact on the exchange rate and direction as tested with several soils. There is a clear tendency toward a release of OCS at higher CO2 levels (up to 7600 ppm), which are typical for the upper few centimeters within soils. At high soil moisture, the release of OCS increased sharply. Measurements after chloroform vapor application show that there is a biotic component to the observed OCS exchange. Furthermore, soil treatment with the fungi inhibitor nystatin showed that fungi might be the dominant OCS consumers in the soils we examined. We discuss the influence of soil moisture and elevated CO2 on the OCS exchange as a change in the activity of microbial communities. Physical factors such as diffusivity that are governed by soil moisture also play a role. Comparing KM values of the enzymes to projected soil water CO2 concentrations showed that competitive inhibition is unlikely for carbonic anhydrase and PEPCO but might occur for RubisCO at higher CO2 concentrations.
Population of the temperate mosquito, Culex pipiens, decreases in response to habitat climatological changes in future
Authors: Watanabe K. , Fukui S. , Ohta S.
Published: May 2017

Predictions of the temporal distribution of vector mosquitoes are an important issue for human health because the response of mosquito populations to climate change could have implications for the risk of vector‐borne diseases. To elucidate the effects of climate change on mosquito populations inhabiting temperate regions, we developed a Physiology‐based Climate‐driven Mosquito Population model for temperate regions. For accurately reproducing the temporal patterns observed in mosquito populations, the key factors were identified by implementing the combinations of factors into the model. We focused on three factors: the effect of diapause, the positive effect of rainfall on larval carrying capacity, and the negative effect of rainfall as the washout mortality on aquatic stages. For each model, parameters were calibrated using weekly observation data of a Culex pipiens adult population collected in Tokyo, Japan. Based on its likelihood value, the model incorporating diapause, constant carrying capacity, and washout mortality was the best to replicate the observed data. By using the selected model and applying global climate model data, our results indicated that the mosquito population would decrease and adults’ active season would be shortened under future climate conditions. We found that incorporating the washout effect in the model settings or not caused a difference in the temporal patterns in the projected mosquito populations. This suggested that water resources in mosquito habitats in temperate regions should be considered for predicting the risk of vector‐borne diseases in such regions.
Analysis on bioaccumulation of metals in aquatic environment of Beas River Basin: A case study from Kanjli wetland
Authors: Singh Navdeep , Kaur Manpreet , Katnoria Jatinder Kaur
Published: May 2017

Wetlands, the biological filters of the Earth, play an important role in biochemical transformation of various pollutants. Wetland plants, in this direction, help in accumulating various contaminants from aquatic bodies. Considering this, the present study was planned to estimate different metals (Cd, Cu, Cr, Co, Fe, Pb, Zn, and Mn) in water, sediment, soil, and plant (4 aquatic and 12 terrestrial) samples of Kanjli wetland, Kapurthala, Punjab (India), and a Ramsar site. It was observed that the contents of Cd and Pb in water samples were higher than limits prescribed by Bureau of Indian standards. Bioaccumulation and translocation factors for various metals were also calculated. Although all the plant species were found to be hyperaccumulator for one or the other metal studied, maximum six metals (Cd, Co, Fe, Mn, Pb, and Zn) were bioaccumulated inPanicum antidotaleamong aquatic plant species while (Cd, Cu, Fe, Mn, Pb, and Zn) inLantana camaraandAgeratum conyzoidsamong terrestrial plants species. It is evident that all these plants have potential to phytoremediate various inorganic pollutants and can act as bioindicators. The physicochemical characteristics revealed high biochemical oxygen demand (BOD) and nitrate (NO3) contents and low dissolved oxygen (DO) in water samples while the high content of phosphates in soil and sediment samples.
An application of principal component analysis to the interpretation of ionospheric current systems
Authors: Alken P. , Maute A. , Richmond A. D. , Vanhamäki H. , Egbert G. D.
Published: May 2017

Ionospheric currents are driven by several different physical processes and exhibit complex spatial and temporal structure. Magnetic field measurements of ionospheric sources are often spatially sparse, causing significant challenges in visualizing current flow at a specific time. Standard methods of fitting equivalent current models to magnetic observations, such as line currents, spherical harmonic analysis, spherical cap harmonic analysis, and spherical elementary current systems (SECS), are often unable to capture the full spatial complexity of the currents or require a large number of parameters which cannot be fully determined by the available data coverage. These methods rely on a set of generic basis functions which contain limited information about the geometries of the various ionospheric sources. In this study, we develop new basis functions for fitting ground and satellite measurements, which are derived from physics‐based ionospheric modeling combined with principal component analysis (PCA). The physics‐based modeling provides realistic current flow patterns for all of the primary ionospheric sources, including their daily and seasonal variability. The PCA technique extracts the most relevant spatial geometries of the currents from the model run into a small set of equivalent current modes. We fit these modes to magnetic measurements of the Swarm satellite mission at low and middle latitudes and compare the resulting model with independent measurements and with the SECS approach. We find that our PCA method accurately reproduces features of the equatorial electrojet and Sq current systems with only 10 modes and can predict ionospheric fields far from the data region.
Patient‐Reported Outcomes
Authors: Kammerman Lisa A. , Cappelleri Joseph C. , Bartlett Jonathan
Published: May 2017

Patient‐reported outcome (PRO) data present unique statistical challenges that may not be encountered with other types of endpoints used in randomized clinical trials. Statisticians, with their expertise in the design of clinical trials and the analysis of clinical trial data, contribute to the science of how studies can use PRO endpoints to provide data that are intended to support approval of medical products and PRO labeling claims. This article provides a brief regulatory history of PROs and highlights topics that statisticians who design and analyze clinical studies with PRO endpoints need to consider.

We discuss study design features that may help improve the likelihood of labeling claims for PRO data. Specification of the scientific question and estimand, definition of PRO endpoint, collection of data that aid PRO analyses and interpretation, and multiplicity adjustments are critical elements. In addition, PRO data have distinctive missing data considerations because PRO scores are typically constructed from many items and, often, from daily diary data. We discuss how missing items and missing diary days can affect efficacy analyses. Finally, we provide considerations for the interpretation of PRO results and suggest topics for further statistical research.
Theanine: Its Occurrence and Metabolism in Tea
Authors: Li Ning , de Silva Jacquie
Published: May 2017

Tea is the second most consumed beverage in the world, after water. It is widely regarded as a healthy beverage, associated with cancer prevention, boosting the immune system and mental alertness, although its popularity as a beverage probably has more to do with its pleasant taste and relaxation benefits. These qualities are attributed to a unique neurologically active non‐protein amino acid calledl‐theanine (γ‐ethylamino‐l‐glutamic acid). In this chapter, the authors review the properties of theanine, its occurrence and metabolism in tea. The possible role of theanine in nitrogen transport is discussed. The regulation of theanine levels is reviewed in the context of plant nitrogen metabolism. Particular emphasis is placed on the identification of enzymes involved in the synthesis and metabolism of theanine. Finally, the authors summarize the status of their endeavours to identify candidate genes contributing to the regulation of theanine levels in tea.
Metabolomics Approaches to Advance Understanding of Nitrogen Assimilation and Carbon–Nitrogen Interactions
Authors: Fait Aaron , Sienkiewicz‐Porzucek Agata , Fernie Alisdair R.
Published: May 2017

In the past 10 years, metabolomics has become an integrative and indispensable part of the post‐genomics approach to tackle questions on plant metabolism and its regulation in plants. Nonetheless, the dynamic range of the metabolic intermediates and their qualitative (chemical) diversity hampers the comprehensive analysis of the plant metabolome using one single platform. However, prompted by the increasing interest in routine analysis of the metabolic component, recent significant advances in experimental techniques, analytical technologies and tools for the elaboration of output data have been accomplished. Hence, our capability to identify an increasing number of metabolites and to integrate results from different approaches has greatly improved. Specific to the study of plant nitrogen metabolism, the introduction of metabolomics, alongside with transcriptomics, and metabolic flux analysis emphasized the complexity of the mechanisms regulating its assimilation and metabolism and the indissoluble interaction with carbon metabolism. In this chapter, we introduce the state of the art in metabolomics analytical tools and technologies as well as their employment to improve our understanding of nitrogen–carbon interaction in plants.
Metabolite Analysis and Metabolomics in the Study of Biotrophic Interactions between Plants and Microbes
Authors: Draper John , Rasmussen Susanne , Zubair Hassan
Published: May 2017

Biotrophic plant–microbe interactions depend on the establishment of a nutritional interface allowing nutrient trafficking between plants and microbial symbionts and pathogens. A global re‐programming of host and microbial metabolism is at the core of these interactions, and we summarise in this chapter studies on metabolome and, to add interpretational power, transcriptome changes associated with the establishment and maintenance of a range of plant–microbe associations. Pathogenic fungi of crops cause severe economic losses, and factors resulting in improved crop resistance against infection and disease spread are therefore the subject of extensive research projects. We focus in this chapter on three fungal examples, namelyMagnaporthe grisea(rice blast),Blumeria graminis(powdery mildew) andUstilago maydis(corn smut), and discuss how metabolomics technologies critically improve our understanding of resistant and susceptible interactions. Like pathogens, mutualistic symbionts are heterotrophic organisms and depend on nutrients from their hosts, but unlike pathogens these microbial symbionts rarely cause disease symptoms or host death. In contrast, they can improve plant fitness by providing valuable nutrients or protective metabolites to their hosts, and we present here insights from studies on three exemplar mutualistic interactions, namely nitrogen fixing legume‐rhizobial, phosphorus supplying plant root – arbuscular mycorrhizal and alkaloid‐producing plant shoot –Neotyphodiumspp. endophyte associations. We conclude this chapter with an analysis of similarities and differences of pathogenic and mutualistic interactions from a global metabolic viewpoint, and propose that improved spatial and temporal separation, as well as high‐throughput analytical techniques for low abundance metabolites (e.g. phytohormones), might overcome some current limitations.
Metabolomics of

A
rabidopsis Thaliana
Authors: Beale Michael H. , Sussman Michael R.
Published: May 2017

Since the publication of the complete genome sequence of the model plant
Arabidopsis thaliana,
the precision annotation of the exact function of each gene has become a major research activity. Metabolomic analysis has much to offer in this endeavour and the small physical size and generation time of Arabidopsis make it a particularly attractive system for large‐scale metabolomic data collection and analysis. In this review, we summarize the known phytochemistry of Arabidopsis, with particular emphasis on recent discoveries that indicate that the complexity of this plant's secondary metabolome is much greater than originally realized. We survey how the different analytical technologies, used in metabolomic analysis, are applied to quantify both primary and secondary metabolites of Arabidopsis. The use of isotope labelling to derive empirical formulae for unknown metabolites is highlighted, as is co‐expression analysis of transcriptome and metabolome data, as both of these technologies are well suited to this species. The application of the various techniques to study the molecular plant physiology, genetics and functional genomics of Arabidopsis is reviewed, with particular reference to the use of mutants and other genetic resources, such as recombinant inbred lines.
Progress in Chemometrics and Biostatistics for Plant Applications, or: A Good Red Wine is a Bad White Wine
Authors: Kopka Joachim , Walther Dirk , Allwood J. William , Goodacre Royston
Published: May 2017

In the hunt for novel chemometric and biostatistical tools suitable for the automated mining of large metabolite profiling and fingerprinting data sets, the application of well‐established statistical tools appears to have been neglected. Using a data set that aims to understand the contributions that the metabolome can make to the prediction of the enological quality of white wines from the Palatinate region of Germany, we exemplify the power of ‘simple’ statistical analyses for knowledge generation and repeatable data reduction without loss of relevant information. In view of the many and diverse experimental designs required in plant physiological studies, we emphasize that no generalized standard operation procedure for the statistical data mining of such experiments should be suggested. Instead, a well‐compiled toolbox of simple and enhanced statistical algorithms should be at hand, and this chemometrics ‘zoo’ can be applied in a case‐by‐case decision and sequence. Care should be taken to have more confidence in statistical significance analyses that estimate error probabilities rather than to focus on just a few sample classification tools, such as the omnipresent principal component (PCA) and hierarchical cluster analyses (HCA). These tools, HCA and PCA, are ideal and expertly employed if applied to the non‐biased search for differential or common trends among samples. These tools, however, are less suited for the search of metabolic markers and whilst partial least squares discriminant analysis is often used in metabolomics studies, a lot of studies have been performed in a less than optimal manner with respect to model validation. In this chapter, we discuss the use of the Wilcoxon test, the Kruskal–Wallis test and analyses of variance (ANOVA) for reproducible data reduction and exemplify the caveats of correlation and discriminant analyses. We are convinced that many novel but also already‐established statistical tools should be explored for metabolomic data mining. We suggest decision tree (DT) analyses as a potentially valuable tool for the deduction of classification rules and propose that DT analysis may improve our understanding of conditional interactions between physiological and metabolic responses.
Interactions between Exogenous Magnesia Inclusions with Endogenous Inclusions in a High Alloyed Steel Melt
Authors: Schröder Christina , Fischer Undine , Schmidt Anne , Schmidt Gert , Volkova Olena , Aneziris Christos G.
Published: May 2017

Interactions between exogenous MgO particles and endogenous inclusions on the surface of a high alloyed steel melt have been investigated in situ in a high temperature confocal laser scanning microscope. Exogenous magnesia particle forms immediately a liquid Mg–Si–Al–Ti–Cr phase surrounding the solid particle. The real attraction forces between the liquid layer surrounding MgO particles and endogenous Al2O3 inclusions are determined in the range of 6 × 10−18 N to 1 × 10−16 N. In contrast to earlier investigations with exogenous Al2O3 particles, lower real attraction forces between exogenous and endogenous particle pairs have been observed in comparison to endogenous inclusions pairs.
A Freeze‐Concentration and Polyampholyte‐Modified Liposome‐Based Antigen‐Delivery System for Effective Immunotherapy
Authors: Ahmed Sana , Fujita Satoshi , Matsumura Kazuaki
Published: May 2017

Immunotherapy is an exciting new approach to cancer treatment. The development of a novel freeze‐concentration method is described that could be applicable in immunotherapy. The method involves freezing cells in the presence of pH‐sensitive, polyampholyte‐modified liposomes with encapsulated ovalbumin (OVA) as the antigen. In RAW 264.7 cells, compared to unfrozen, freeze‐concentration of polyampholyte‐modified liposomes encapsulating OVA resulted in efficient OVA uptake and also allowed its delivery to the cytosol. Efficient delivery of OVA to the cytosol was shown to be partly due to the pH‐dependence of the polyampholyte‐modified liposomes. Cytosolic OVA delivery also resulted in significant up‐regulation of the major histocompatibility complex class I pathway through cross‐stimulation, as well as an increase in the release of IL‐1β, IL‐6, and TNF‐α. The results demonstrate that the combination of a simple freeze‐concentration method and polyampholyte‐modified liposomes might be useful in future immunotherapy applications.
Conductivity Enhancement of PEDOT:PSS via Addition of Chloroplatinic Acid and Its Mechanism
Authors: Wu Falin , Li Pengcheng , Sun Kuan , Zhou Yongli , Chen Wei , Fu Jiehao , Li Meng , Lu Shirong , Wei Dongshan , Tang Xiaosheng , Zang Zhigang , Sun Lidong , Liu Xixia , Ouyang Jianyong
Published: May 2017

Readily obtained highly conductive, transparent, and flexible poly(3,4‐ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) films is urgently needed in printing of flexible transparent electrodes. A simple and facile method to enhance the electrical conductivity of PEDOT:PSS films is reported. The conductivity is increased by four orders of magnitude after adding solid chloroplatinic acid (H2PtCl6) into the pristine PEDOT:PSS solution. The H2PtCl6‐doped PEDOT:PSS film exhibits a sheet resistance of 44 ± 5 Ω □‐1 and a transmittance of 84 ± 1% at 550 nm, corresponding to a figure of merit of 47 ± 4. Comparative study shows addition of solid acid like H2PtCl6 is more effective in conductivity enhancement than addition of polar organic solvents, such as dimethyl sulfoxide or ethylene glycol. The mechanism for the conductivity enhancement is attributed to both in situ doping and phase separation of PEDOT:PSS. PEDOT is oxidized and doped by Pt4+ of H2PtCl6, which is reduced simultaneously to Pt2+. Proton transfer from H2PtCl6 to PSS− of PEDOT:PSS causes formation of neutral PSSH, leading to phase separation between insulating PSS and conducting PEDOT. Such a phase separation results in conformational changes of PEDOT chains and reduction in energy barrier for charge hopping.
Multistep Photoluminescence Decay Reveals Dissociation of Geminate Charge Pairs in Organolead Trihalide Perovskites
Authors: Augulis Ramūnas , Franckevičius Marius , Abramavičius Vytautas , Abramavičius Darius , Zakeeruddin Shaik Mohammed , Grätzel Michael , Gulbinas Vidmantas
Published: May 2017

Charge carrier dynamics in organolead iodide perovskites is analyzed by employing time‐resolved photoluminescence spectroscopy with several ps time resolution. The measurements performed by varying photoexcitation intensity over five orders of magnitude enable separation of photoluminescence components related to geminate and nongeminate charge carrier recombination and to address the dynamics of an isolated geminate electron–hole pair. Geminate recombination dominates at low excitation fluence and determines the initial photoluminescence decay. This decay component is remarkably independent of the material structure and experimental conditions. It is demonstrated that dependences of the geminate and nongeminate radiative recombination components on excitation intensity, repetition rate, and temperature, are hardly compatible with carrier trapping and exciton dissociation models. On the basis of semiclassical and quantum mechanical numerical calculation results, it is argued that the fast photoluminescence decay originates from gradual spatial separation of photogenerated weakly bound geminate charge pairs.
Understanding and Eliminating Hysteresis for Highly Efficient Planar Perovskite Solar Cells
Authors: Wang Changlei , Xiao Chuanxiao , Yu Yue , Zhao Dewei , Awni Rasha A. , Grice Corey R. , Ghimire Kiran , Constantinou Iordania , Liao Weiqiang , Cimaroli Alexander J. , Liu Pei , Chen Jing , Podraza Nikolas J. , Jiang Chun‐Sheng , Al‐Jassim Mowafak M. , Zhao Xingzhong , Yan Yanfa
Published: May 2017

Through detailed device characterization using cross‐sectional Kelvin probe force microscopy (KPFM) and trap density of states measurements, we identify that the J–V hysteresis seen in planar organic–inorganic hybrid perovskite solar cells (PVSCs) using SnO2 electron selective layers (ESLs) synthesized by low‐temperature plasma‐enhanced atomic‐layer deposition (PEALD) method is mainly caused by the imbalanced charge transportation between the ESL/perovskite and the hole selective layer/perovskite interfaces. We find that this charge transportation imbalance is originated from the poor electrical conductivity of the low‐temperature PEALD SnO2 ESL. We further discover that a facile low‐temperature thermal annealing of SnO2 ESLs can effectively improve the electrical mobility of low‐temperature PEALD SnO2 ESLs and consequently significantly reduce or even eliminate the J–V hysteresis. With the reduction of J–V hysteresis and optimization of deposition process, planar PVSCs with stabilized output powers up to 20.3% are achieved. The results of this study provide insights for further enhancing the efficiency of planar PVSCs.
Correlates of resistance and relapse during blinatumomab therapy for relapsed/refractory acute lymphoblastic leukemia
Authors: Aldoss Ibrahim , Song Joo , Stiller Tracey , Nguyen Tina , Palmer Joycelynne , O'Donnell Margaret , Stein Anthony S. , Marcucci Guido , Forman Stephen , Pullarkat Vinod
Published: May 2017

We retrospectively analyzed 65 patients with refractory/relapsed (r/r) ALL who were treated with blinatumomab for predictors of leukemia response as well as clinical patterns of relapse and resistance with particular focus on downregulation of CD19 expression and extramedullary disease (EM‐ALL). The complete remission (CR) rate was 51%, and 15 (45%) responders underwent allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden (bone marrow blasts >50%) (P = .02), history of prior EM‐ALL (P = .005), and active EM‐ALL at the time of initiating blinatumomab (P = .05) predicted lower CR rate. Among refractory cases, 13 (41%) had evidence of EM‐ALL progression, and CD19 expression was negative or dim in 18% and 23%, respectively. Among responders, 20 (61%) subsequently relapsed among whom EM‐ALL relapse occurred in 8 (40%) patients, and CD19 expression was negative or dim in 35 and 6% of evaluable cases, respectively. Pretreatment moderate/strong CD19 expression (P = .01) and history of prior EM‐ALL during ALL course (P = .04) were risk factors for developing EM‐ALL at progression/relapse. However, no pretreatment factors predicted progression/relapse with CD19‐negative ALL. Overall‐survival (OS) and even‐free survival were improved for patients underwent allogeneic HCT compared to responders who did not. Furthermore, OS was superior for patients responded to blinatumomab compared to those who did not. Extramedullary and CD19‐negative disease are common during blinatumomab failure in r/r ALL. In addition to high leukemia burden, concurrent or prior history EM‐ALL were associated with lower response to blinatumomab. Higher CD19 expression as well as prior history of EM‐ALL were associated with EM‐ALL at the time of blinatumomab failure.
Local integrals of motion in many‐body localized systems
Authors: Imbrie John Z. , Ros Valentina , Scardicchio Antonello
Published: May 2017

We review the current (as of Fall 2016) status of the studies on the emergent integrability in many‐body localized models. We start by explaining how the phenomenology of fully many‐body localized systems can be recovered if one assumes the existence of a complete set of (quasi)local operators which commute with the Hamiltonian (local integrals of motions, or LIOMs). We describe the evolution of this idea from the initial conjecture, to the perturbative constructions, to the mathematical proof given for a disordered spin chain. We discuss the proposed numerical algorithms for the construction of LIOMs and the status of the debate on the existence and nature of such operators in systems with a many‐body mobility edge, and in dimensions larger than one.

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Single‐mode distributed feedback laser operation with no dependence on the morphology of the gain medium
Authors: Umar Muhammad , Min Kyungtaek , Jeon Heonsu , Kim Sunghwan
Published: May 2017

Organic distributed feedback (DFB) lasers can be useful photonic tools for biological applications where the roles of organic materials are important, because highly coherent single mode emission with broad tuning range can be obtained. However, the formulaic structures of organic lasers, and the uses of gain media as resonators themselves, are not suitable for inducing laser emission from irregular shaped gain media, such as dye‐staining cells and tissues. Here, we report a reusable photonic template comprising an exceedingly thin and discrete titanium dioxide (TiO2) layer on a one‐dimensional (1D) quartz grating to induce single mode DFB lasing from a variety of states of optical gain media. Using the same template, the external gain media of optically thick and thin casted film, liquid, and a free‐standing thick film reveal single mode lasing with reliable performance. Numerical simulations demonstrate that the 25‐nm thick TiO2 disconnected grating lines support a spatially confined DFB mode in the vertical direction, even under no index difference between superstrate and substrate. Additionally, not using the typical waveguide gain layer promises high sensitivity and detection limit in refractometric sensing. These results suggest that the photonic structure may serve as a versatile sensing platform for bioapplications.
The Dynamic Multisite Interactions between Two Intrinsically Disordered Proteins
Authors: Wu Shaowen , Wang Dongdong , Liu Jin , Feng Yitao , Weng Jingwei , Li Yu , Gao Xin , Liu Jianwei , Wang Wenning
Published: May 2017

Protein interactions involving intrinsically disordered proteins (IDPs) comprise a variety of binding modes, from the well‐characterized folding upon binding to dynamic fuzzy complexes. To date, most studies concern the binding of an IDP to a structured protein, while the interaction between two IDPs is poorly understood. In this study, NMR, smFRET, and molecular dynamics (MD) simulation are combined to characterize the interaction between two IDPs, the C‐terminal domain (CTD) of protein 4.1G and the nuclear mitotic apparatus (NuMA) protein. It is revealed that CTD and NuMA form a fuzzy complex with remaining structural disorder. Multiple binding sites on both proteins were identified by molecular dynamics and mutagenesis studies. This study provides an atomic scenario in which two IDPs bearing multiple binding sites interact with each other in dynamic equilibrium. The combined approach employed here could be widely applicable for investigating IDPs and their dynamic interactions.
Synthesis of phenanthridine and phenanthridinone derivatives based on Pd‐catalyzed C–H activation
Authors: Rafiee Fatemeh
Published: May 2017

This review article provides an overview of the most recent and exciting developments in palladium‐catalyzed C–H activation and mechanistic aspects of these catalytic reactions as the fast‐growing field for the synthesis of phenanthridine derivatives.
Direct synthesis of Fe(III) immobilized Zr‐based metal–organic framework for aerobic oxidation reaction
Authors: Shu Xin , Yu Ying , Jiang Yi , Luan Yi , Ramella Daniele
Published: May 2017

A Zr‐based metal–organic framework with bipyridine units (UiO‐67) has been utilized for the immobilization of catalytically active iron species via a post‐synthetic metalation method. UiO‐67 bipyridine MOF was synthesized through a simple solvothermal method and was shown to have a UiO‐type structure. Post‐synthetic metalation of UiO‐67 MOF was performed for the immobilization of the catalytically active FeCl3. FT‐IR and EDX element map suggested that FeCl3 is coordinately bonded to the UiO‐67 bipyridine framework. The synthesized UiO‐67‐FeCl3 catalyst was used for the aerobic oxidation of alcohols and benzylic compounds in the presence of molecular oxygen. In addition, the UiO‐67‐FeCl3 catalyst can be reused as a solid heterogeneous catalyst without compromising its activity and selectivity.
High‐k dielectric composites of poly(2‐cyanoethyl vinyl ether) and barium titanate for flexible electronics
Authors: Piana Francesco , Pfleger Jiří , Jambor Roman , Řičica Tomáš , Macak Jan M.
Published: May 2017

High‐k dielectric composite material for electronic applications was obtained by mixing a polymer with high dielectric constant, poly(2‐cyanoethyl vinyl ether) (CEPVA), and highly crystalline barium titanate (BT). Barium titanate nanoparticles of a size in the range 40–90 nm were prepared by the solvothermal method. By optimizing the reaction conditions, the formation of carbonate impurities and the agglomeration of formed nanoparticles were significantly reduced compared to state‐of‐the‐art procedures. Dielectric spectroscopy was measured in the range of 0.01 Hz to 10 MHz and showed the dielectric constant to be ɛ′ ∼ 35–40 with only 30 vol % content of BT in the composite. Extrapolating to 100% BT nanoparticle concentration and using the Lichtenecker model, the dielectric constant ɛ′ = 365 ± 27 at 10 kHz was obtained. The relaxation and electrical properties were investigated in depth, and a new relaxation phenomenon was revealed. CEPVA/BT composite is considered suitable for electronic applications, in which high ɛ′ together with a good mechanical flexibility are required, such as organic field effect transistors. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45236.
Physico‐optical properties of a crosslinked hyaluronic acid scaffold for biomedical applications
Authors: Lepore Maria , Portaccio Marianna , Delfino Ines , Sironi Laura , La Gatta Annalisa , D'Agostino Antonella , Izzo E. , Schiraldi Chiara
Published: May 2017

Optical techniques are increasingly employed for monitoring cell–matrix interactions in suitably prepared 3D scaffolds. The ability of designing and realizing synthetic extracellular matrix with well‐controlled optical properties is a crucial need in this field. For this purpose, a crosslinked hyaluronic acid (HA) scaffold is prepared. Fourier transform infrared and ultraviolet–visible spectroscopies enable to monitor the scaffold preparation process and to evidence scaffold high transparency and low fluorescence in the visible range. 3D optical characteristics of the HA scaffold are tested by two‐photon microscopy (TPM) imaging of embedded fluorescent microbeads and alive keratinocytes labeled with vital PKH67 dye at different depths from the scaffold surface. Some useful indications about the potentiality of TPM measurements for the determination of attenuation coefficient of turbid media are also reported. Moreover, the use of the presented HA scaffold for preparing tissue phantoms for fluorescence imaging or diffuse imaging is proposed. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45243.
Current Advances in Highly Multiplexed Antibody‐Based Single‐Cell Proteomic Measurements
Authors: Huang Lu , Michael Sean A. , Chen Yangfan , Wu Hongkai
Published: May 2017

Single‐cell measurements have played a critical role in revealing the complex signaling dynamics and heterogeneity present in cells, but there is still much to learn. Measuring samples from bulk populations of cells often masks the information and dynamics present in subsets of cells. Common single‐cell protein studies rely on fluorescent microscopy and flow cytometry but are limited in multiplexing ability owing to spectral overlap. Recently, technology advancements in single‐cell proteomics have allowed highly multiplexed measurement of multiple parameters simultaneously by using barcoded microfluidic enzyme‐linked immunosorbent assays and mass cytometry techniques. In this review, we will describe recent work around multiparameter single‐cell protein measurements and critically analyze the techniques.
UHPLC‐ESI‐MS/MS determination and pharmacokinetics of pinoresinol glucoside and chlorogenic acid in rat plasma after oral administration of Eucommia ulmoides Oliv extract
Authors: Gong Xiaojian , Luan Qingxiang , Zhou Xin , Zhao Yang , Zhao Chao
Published: May 2017

This study aimed to develop a specific UHPLC‐ESI‐MS/MS method for simultaneous determination and pharmacokinetics of pinoresinol glucoside and chlorogenic acid in rat plasma after oral administration of Eucommia ulmoides. The chromatographic separation was achieved on a Hypersil GOLD column with gradient elution by using a mixture of 0.1% formic acid aqueous solution and acetonitrile as the mobile phase at a flow rate of 200 μL/min. A tandem mass spectrometric detection was conducted using multiple‐reaction monitoring via an electrospray ionization source in negative ionization mode. Samples were pre‐treated by a single‐step protein precipitation with acetonitrile, and bergenin was used as internal standard. After oral administration of 3 mL/kg E. ulmoides extract in rats, the maximum plasma concentrations of pinoresinol glucoside and chlorogenic acid were 57.44 and 61.04 ng/mL, respectively. The times to reach the maximum plasma concentration were 40.00 and 23.33 min for pinoresinol glucoside and chlorogenic acid, respectively. The intra‐ and inter‐day precision (RSD) values for the two analytes were <2.46 and 5.15%, respectively, and the accuracy (RE) values ranged from −12.76 to 0.00. This is the first study on pharmacokinetics of bioactive compounds in rat plasma after oral administration of E. ulmoides extract.
Predicting the optimum compositions of a transdermal nanoemulsion system containing an extract of Clinacanthus nutans leaves (L.) for skin antiaging by artificial neural network model
Authors: Che Sulaiman Intan Soraya , Basri Mahiran , Fard Masoumi Hamid Reza , Ashari Siti Efliza , Basri Hamidon , Ismail Maznah
Published: May 2017

A nanoemulsion‐based formulation containing leaf extracts of Clinacanthus nutans Lindau (C. nutans) was prepared for therapeutic use and optimized by artificial neural network (ANN). The model was applied to optimize the particle size of the transdermal nanoemulsion system containing an extract of C. nutans leaves for skin antiaging. Five universal learning algorithms—incremental back propagation, batch back propagation, quick propagation, genetic algorithm, and Levenberg‐Marquardt—were used in the ANN to achieve the optimum topologies. The optimum topologies were selected among the learning algorithms trained with lowest root mean square values. Genetic Algorithm‐5‐13‐1 was found to be the optimum topology for the final model to predict the optimum particle size. Under these conditions, the actual particle size of the optimum nanoemulsion compared well with the predicted values with the residual standard error of less than 1.5%. The final formulation was observed to be stable against phase separation under an accelerated stability study and during storage at room temperature and 45°C for 90 days. The dermal irritation assay demonstrated that the developed nanoemulsion was found to be compatible with human skin and could be classified as nonirritant. In vivo ultrasound attributes of the skin study showed that the collagen content increased significantly with the application of the C. nutans nanoemulsion among all 21 volunteers during the 21 days of the treatment period. Hence, ANN was found to be an effective tool for optimizing the nanoemulsion containing C. nutans leaves extract with efficacy to protect collagen from breakdown.
Highly Active and Iso‐Selective Catalysts for the Ring‐Opening Polymerization of Cyclic Esters using Group 2 Metal Initiators
Authors: Bhattacharjee Jayeeta , Harinath Adimulam , Nayek Hari Pada , Sarkar Alok , Panda Tarun K.
Published: May 2017

A series of alkali and alkaline earth (Ae) metal complexes bearing 1,2‐phenylene(bis‐diphenylphosphinothioic/selenoic amine) [{Ph2P(E)NH}2C6H4] (E=S (1‐H2); Se (2‐H2) ligands are reported. Alkali metal complexes [{Ph2P(S)N}2C6H4]Na(THF)4 (3 a) [{Ph2P(Se)N}2C6H4]Na(THF)4 (3 b), and [{Ph2P(Se)N}2C6H4]K(THF)5 (4 b) were obtained in good yield by treating protic ligands 1‐H2 or 2‐H2 with metal hexamethyldisilazides [MN(SiMe3)2] (M=Na or K) at ambient temperature. The Ae metal complexes formulated as [{Ph2P(E)N}2C6H4]M(THF)3 [E=S, M=Ca (5 a), Sr (6 a), Ba (7 a); E=Se, M=Ca (5 b), Sr (6 b), Ba (7 b)] can be synthesized by using two routes. The molecular structures of the free ligand 1‐H2 and metal complexes 5 a,b–7 a,b in their solid states were established. Complexes 3 a and 3 b are isostructural; however, in complex 4 b, an attachment different from ligand 2 was observed. The complexes 5 a,b–7 a,b are isostructural and each metal ion exhibits a distorted pentagonal bipyramidal geometry around it. All Ae metal complexes 5 a,b–7 a,b were tested for the ring‐opening polymerization (ROP) of racemic lactide (rac‐LA) and ϵ‐caprolactone (ϵ‐CL) at room temperature. Calcium complexes 5 a and 5 b show excellent iso‐selectivity, with Pi values of 0.78–0.87 at 298 K and with a high degree of polymerization control, whereas the corresponding strontium complexes 6 a and 6 b exhibit moderate iso‐selectivity, and barium complexes 7 a and 7 b yield only atactic polylactides (PLAs). In all cases, the catalyst initiates the ROP catalytic cycle in the absence of any external initiator. Kinetic studies of the polymerization reactions indicate the relative order of polymerization rate increases with increase in the size of the metal ion: Ba>Sr>Ca.
Coordination Behavior of [Cp′′2Zr(η1:1‐P4)] towards Different Lewis Acids
Authors: Seitz Andreas E. , Vogel Ulf , Eberl Miriam , Eckhardt Maria , Balázs Gábor , Peresypkina Eugenia V. , Bodensteiner Michael , Zabel Manfred , Scheer Manfred
Published: May 2017

A detailed method for the preparation of [Cp′′2Zr(η1:1‐P4)] (1) is presented. The coordination behavior of 1 towards Lewis acidic transition metal complexes of tungsten, manganese, and iron, respectively, and main group compounds (AlMe3, AlEt3) was investigated in detail by computational and experimental studies. In doing so, a series of unprecedented complexes with different coordination modes and multiple coordination numbers of the tetraphosphabicyclo[1.1.0]butane framework were synthesized. All products, as well as the starting materials, were comprehensively characterized by NMR spectroscopy, mass spectrometry, elemental analysis, and single crystal X‐ray structural analysis.
Direct Observation of Confined I−⋅⋅⋅I2⋅⋅⋅I− Interactions in a Metal–Organic Framework: Iodine Capture and Sensing
Authors: Hu Yue‐Qiao , Li Mu‐Qing , Wang Yanyan , Zhang Tao , Liao Pei‐Qin , Zheng Zhiping , Chen Xiao‐Ming , Zheng Yan‐Zhen
Published: May 2017

Herein a strategy is reported for capturing and sensing iodine by strong I−⋅⋅⋅I2⋅⋅⋅I− interaction, confined in a metal‐organic framework, [Tb(Cu4I4)(ina)3(DMF)] (1) (ina=isonicotinate). As revealed by single‐crystal X‐ray crystallography, the uptaken I2 molecules directly contact the {Cu4I4}n chains, virtually forming an electronically polarizable tetraiodide anion (I42−) through strong I−⋅⋅⋅I2⋅⋅⋅I− interaction. As such, a quasi‐copper‐iodide layer of {Cu4I5}n with semiconducting characteristics results, leading to a significant enhancement (Δσ=107 times) in electrical conductivity over the I2‐free 1. The effect observed is several orders of magnitude higher than those reported due to iodine⋅⋅⋅aromatic interactions (Δσ=102 times) and by interactions between I2 and a redox‐active metal centre (Δσ=104 times). The drastic enhancement in electrical conductivity was used to switch on/off an LED bulb, suggesting the possibility of electrically sensing I2.
Elektrotauchlackierung
Authors: Brock Thomas
Published: May 2017

Die Elektrotauchlackierung ist ein modernes Lackierverfahren zur organischen Beschichtung insbesondere von komplex geformten Metallteilen mittels elektrischen Gleichstroms. Das Prinzip der Elektrotauchlackierung beruht auf der Entladung und sich anschließenden Abscheidung von Polymerionen auf einem als Elektrode dienenden metallenen Untergrund. Das nachfolgende Einbrennen mit physikalischer Filmbildung und chemischer Vernetzung führt zu einem hervorragendem Korrosionsschutz und weiteren chemischen und mechanischen Schutzeigenschaften. Die extrem gleichmäßige Schichtausbildung sogar in Hohlräumen beruht auf dem zunehmenden elektrischen Widerstand von abgeschiedenem und verdichtetem Lackmaterial auf der Metalloberfläche.
Identification of α7 Nicotinic Acetylcholine Receptor Silent Agonists Based on the Spirocyclic Quinuclidine‐Δ2‐Isoxazoline Scaffold: Synthesis and Electrophysiological Evaluation
Authors: Quadri Marta , Matera Carlo , Silnović Almin , Pismataro Maria Chiara , Horenstein Nicole A. , Stokes Clare , Papke Roger L. , Dallanoce Clelia
Published: May 2017

Compound 11 (3‐(benzyloxy)‐1′‐methyl‐1′‐azonia‐4H‐1′‐azaspiro[isoxazole‐5,3′‐bicyclo[2.2.2]octane] iodide) was selected from a previous set of nicotinic ligands as a suitable model compound for the design of new silent agonists of α7 nicotinic acetylcholine receptors (nAChRs). Silent agonists evoke little or no channel activation but can induce the α7 desensitized Ds state, which is sensitive to a type II positive allosteric modulator, such as PNU‐120596. Introduction of meta substituents into the benzyloxy moiety of 11 led to two sets of tertiary amines and quaternary ammonium salts based on the spirocyclic quinuclidinyl‐Δ2‐isoxazoline scaffold. Electrophysiological assays performed on Xenopus laevis oocytes expressing human α7 nAChRs highlighted four compounds that are endowed with a significant silent‐agonism profile. Structure–activity relationships of this group of analogues provided evidence of the crucial role of the positive charge at the quaternary quinuclidine nitrogen atom. Moreover, the present study indicates that meta substituents, in particular halogens, on the benzyloxy substructure direct specific interactions that stabilize a desensitized conformational state of the receptor and induce silent activity.