bluuebunny/crossref_metadata_2025 huggingface dataset:
Remarkable Enhancement of the Hole Mobility in Several Organic Small‐Molecules, Polymers, and Small‐Molecule:Polymer Blend Transistors by Simple Admixing of the Lewis Acid p‐Dopant B(C6F5)3
Authors: Panidi Julianna , Paterson Alexandra F. , Khim Dongyoon , Fei Zhuping , Han Yang , Tsetseris Leonidas , Vourlias George , Patsalas Panos A. , Heeney Martin , Anthopoulos Thomas D.
Published: October 2017

Improving the charge carrier mobility of solution‐processable organic semiconductors is critical for the development of advanced organic thin‐film transistors and their application in the emerging sector of printed electronics. Here, a simple method is reported for enhancing the hole mobility in a wide range of organic semiconductors, including small‐molecules, polymers, and small‐molecule:polymer blends, with the latter systems exhibiting the highest mobility. The method is simple and relies on admixing of the molecular Lewis acid B(C6F5)3 in the semiconductor formulation prior to solution deposition. Two prototypical semiconductors where B(C6F5)3 is shown to have a remarkable impact are the blends of 2,8‐difluoro‐5,11‐bis(triethylsilylethynyl)anthradithiophene:poly(triarylamine) (diF‐TESADT:PTAA) and 2,7‐dioctyl[1]‐benzothieno[3,2‐b][1]benzothiophene:poly(indacenodithiophene‐co‐benzothiadiazole) (C8‐BTBT:C16‐IDTBT), for which hole mobilities of 8 and 11 cm2 V−1 s−1, respectively, are obtained. Doping of the 6,13‐bis(triisopropylsilylethynyl)pentacene:PTAA blend with B(C6F5)3 is also shown to increase the maximum hole mobility to 3.7 cm2 V−1 s−1. Analysis of the single and multicomponent materials reveals that B(C6F5)3 plays a dual role, first acting as an efficient p‐dopant, and secondly as a microstructure modifier. Semiconductors that undergo simultaneous p‐doping and dopant‐induced long‐range crystallization are found to consistently outperform transistors based on the pristine materials. Our work underscores Lewis acid doping as a generic strategy towards high performance printed organic microelectronics.
18F‐flortaucipir tau positron emission tomography distinguishes established progressive supranuclear palsy from controls and Parkinson disease: A multicenter study
Authors: Schonhaut Daniel R. , McMillan Corey T. , Spina Salvatore , Dickerson Bradford C. , Siderowf Andrew , Devous Michael D. , Tsai Richard , Winer Joseph , Russell David S. , Litvan Irene , Roberson Erik D. , Seeley William W. , Grinberg Lea T. , Kramer Joel H. , Miller Bruce L. , Pressman Peter , Nasrallah Ilya , Baker Suzanne L. , Gomperts Stephen N. , Johnson Keith A. , Grossman Murray , Jagust William J. , Boxer Adam L. , Rabinovici Gil D.
Published: October 2017

Objective

18F‐flortaucipir (formerly 18F‐AV1451 or 18F‐T807) binds to neurofibrillary tangles in Alzheimer disease, but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo 18F‐flortaucipir uptake in patients meeting clinical research criteria for PSP (n = 33) to normal controls (n = 46) and patients meeting criteria for Parkinson disease (PD; n = 26).

Methods

Participants underwent magnetic resonance imaging and positron emission tomography for amyloid‐β (11C‐PiB or 18F‐florbetapir) and tau (18F‐flortaucipir). 18F‐flortaucipir standardized uptake value ratios were calculated (t = 80–100 minutes, cerebellum gray matter reference). Voxelwise and region‐of‐interest group comparisons were performed in template space, with receiver operating characteristic curve analyses to assess single‐subject discrimination. Qualitative comparisons with postmortem tau are reported in 1 patient who died 9 months after 18F‐flortaucipir.

Results

Clinical PSP patients showed bilaterally elevated 18F‐flortaucipir uptake in globus pallidus, putamen, subthalamic nucleus, midbrain, and dentate nucleus relative to controls and PD patients (voxelwise p < 0.05 family wise error corrected). Globus pallidus binding best distinguished PSP patients from controls and PD (area under the curve [AUC] = 0.872 vs controls, AUC = 0.893 vs PD). PSP clinical severity did not correlate with 18F‐flortaucipir in any region. A patient with clinical PSP and pathological diagnosis of corticobasal degeneration had severe tau pathology in PSP‐related brain structures with good correspondence between in vivo 18F‐flortaucipir and postmortem tau neuropathology.

Interpretation

18F‐flortaucipir uptake was elevated in PSP versus controls and PD patients in a pattern consistent with the expected distribution of tau pathology. Ann Neurol 2017;82:622–634
Organic Thiocarboxylate Electrodes for a Room‐Temperature Sodium‐Ion Battery Delivering an Ultrahigh Capacity
Authors: Zhao Hongyang , Wang Jianwei , Zheng Yuheng , Li Ju , Han Xiaogang , He Gang , Du Yaping
Published: October 2017

Organic room‐temperature sodium‐ion battery electrodes with carboxylate and carbonyl groups have been widely studied. Herein, for the first time, we report a family of sodium‐ion battery electrodes obtained by replacing stepwise the oxygen atoms with sulfur atoms in the carboxylate groups of sodium terephthalate which improves electron delocalization, electrical conductivity and sodium uptake capacity. The versatile strategy based on molecular engineering greatly enhances the specific capacity of organic electrodes with the same carbon scaffold. By introducing two sulfur atoms to a single carboxylate scaffold, the molecular solid reaches a reversible capacity of 466 mAh g−1 at a current density of 50 mA g−1. When four sulfur atoms are introduced, the capacity increases to 567 mAh g−1 at a current density of 50 mA g−1, which is the highest capacity value reported for organic sodium‐ion battery anodes until now.
Conformational Selection of Dimethylarginine Recognition by the Survival Motor Neuron Tudor Domain
Authors: Supekar Shreyas , Papageorgiou Anna C. , Gemmecker Gerd , Peltzer Raphael , Johansson Mikael P. , Tripsianes Konstantinos , Sattler Michael , Kaila Ville R. I.
Published: October 2017

Tudor domains bind to dimethylarginine (DMA) residues, which are post‐translational modifications that play a central role in gene regulation in eukaryotic cells. NMR spectroscopy and quantum calculations are combined to demonstrate that DMA recognition by Tudor domains involves conformational selection. The binding mechanism is confirmed by a mutation in the aromatic cage that perturbs the native recognition mode of the ligand. General mechanistic principles are delineated from the combined results, indicating that Tudor domains utilize cation–π interactions to achieve ligand recognition.
Cetacean rapid assessment: An approach to fill knowledge gaps and target conservation across large data deficient areas
Authors: Braulik Gill T. , Kasuga Magreth , Wittich Anja , Kiszka Jeremy J. , MacCaulay Jamie , Gillespie Doug , Gordon Jonathan , Said Said Shaib , Hammond Philip S.
Published: October 2017

Many species and populations of marine megafauna are undergoing substantial declines, while many are also very poorly understood. Even basic information on species presence is unknown for tens of thousands of kilometres of coastline, particularly in the developing world, which is a major hurdle to their conservation.

Rapid ecological assessment is a valuable tool used to identify and prioritize areas for conservation; however, this approach has never been clearly applied to marine cetaceans. Here a rapid assessment protocol is outlined that will generate broad‐scale, quantitative, baseline data on cetacean communities and potential threats, that can be conducted rapidly and cost‐effectively across whole countries, or regions.

The rapid assessment was conducted in Tanzania, East Africa, and integrated collection of data on cetaceans from visual, acoustic, and interview surveys with existing information from multiple sources, to provide low resolution data on cetacean community relative abundance, diversity, and threats. Four principal threats were evaluated and compared spatially using a qualitative scale: cetacean mortality in fishing gear (particularly gillnets); cetacean hunting, consumption or use by humans; shipping related collision risk and noise disturbance; and dynamite fishing.

Ninety‐one groups of 11 species of marine mammal were detected during field surveys. Potentially the most important area for cetaceans was the Pemba Channel, a deep, high‐current waterway between Pemba Island and mainland Africa, where by far the highest relative cetacean diversity and high relative abundance were recorded, but which is also subject to threats from fishing.

A rapid assessment approach can be applied in data deficient areas to quickly provide information on cetaceans that can be used by governments and managers for marine spatial planning, management of developments, and to target research activities into the most important locations.
Polymorph‐Dependent Green, Yellow, and Red Emissions of Organic Crystals for Laser Applications
Authors: Xu Zhenzhen , Zhang Zhiwei , Jin Xue , Liao Qing , Fu Hongbing
Published: October 2017

Color tuning of organic solid‐state luminescent materials remains difficult and time‐consuming through conventional chemical synthesis. Herein, we reported highly efficient polymorph‐dependent green (P1), yellow (P2), and red (P3) emissions of organic crystals made by the same molecular building blocks of 4‐(2‐{4‐[2‐(4‐diphenylamino‐phenyl)‐vinyl]‐phenyl}‐vinyl)‐benzonitrile (DOPVB). Single‐crystal X‐ray diffraction (XRD) and spectroscopic data reveal that all three polymorphs follow the herringbone packing motif in H‐type aggregations. On the one hand, from P1, P2 to P3, the reduced pitch translation along π stacks increases the intermolecular interactions between adjacent molecules, therefore leading to gradually red‐shifted emissions from 540, 570 to 614 nm. On the other hand, the edge‐to‐face arrangement and large roll translations avoid strong π–π overlap, making P1, P2 and P3 highly emissive with record‐high solid‐state fluorescence quantum yields of 0.60, 0.98, and 0.68, respectively. Furthermore, the optically allowed 0–1 transitions of herringbone H‐aggregates of P1, P2 and P3 naturally provide a four‐level scheme, enabling green and yellow amplified spontaneous emissions (ASE) with very low thresholds.
Considerations on how to investigate planes of satellite galaxies
Authors: Pawlowski Marcel S. , Dabringhausen Jörg , Famaey Benoit , Flores Hector , Hammer François , Hensler Gerhard , Ibata Rodrigo A. , Kroupa Pavel , Lewis Geraint F. , Libeskind Noam I. , McGaugh Stacy S. , Merritt David , Puech Mathieu , Yang Yanbin
Published: October 2017

The existence of a spatially thin, kinematically coherent Disk of Satellites (DoS) around the Milky Way (MW) is a problem that often garners vivacious debate in the literature or at scientific meetings. One of the most recent incarnations of this wrangle occurred with two papers by Maji et al., who argued that these structures “may be a misinterpretation of the data.” These claims are in stark contrast to previous works. Motivated by this and other recent publications on this problem, we discuss necessary considerations to make, observational effects to consider, and pitfalls to avoid when investigating satellite galaxy planes such as the MW's DoS. In particular, we emphasize that conclusions need to have a statistical basis including a determination of the significance of satellite alignments, observational biases must not be ignored, and measurement errors (e.g., for proper motions) need to be considered. We discuss the general problems faced by attempts to determine the dynamical stability of the DoS via orbit integrations of MW satellite galaxies, and demonstrate that, to interpret simulations, it is helpful to compare them with a null case of isotropically distributed satellite positions and velocities. Based on these criteria, we find that the conclusions of Maji et al. do not hold up to scrutiny, and that their hydrodynamic cosmological simulation of a single host shows no evidence for a significant kinematic coherence among the simulated satellite galaxies, in contrast to the observed MW system.
Entwicklung von thermischen Gebäudelastprofilen für die Dimensionierung von Wärmeerzeugern und zur Simulation von Nahwärmenetzen
Authors: Weißmann Claudia , Wörner Patrick
Published: October 2017

Herrn Univ.‐Prof. Dr.‐Ing. Carl‐Alexander Graubner zum 60. Geburtstag gewidmet.

Vor dem Hintergrund der Energiewende wird in Gebäuden und Quartieren der klassische gasbetriebene Heizkessel zunehmend durch eine Vielzahl von Wärmeerzeugern ersetzt. Um eine effi ziente Dimensionierung dieser Anlagensysteme in der Planungsphase vornehmen zu können, ist es von Vorteil, wenn der Wärmebedarf des Gebäudes zu kleinen Zeitschritten bekannt ist. Zu diesem Zweck eignen sich thermische Lastprofile, die in Form von Datensätzen in softwaregestütze Modelle zur Berechnung des Anlagenbetriebs implementiert werden können. Im Rahmen dieses Beitrags werden 15‐Minuten‐basierte, gebäudespezifische thermische Lastprofile mittels der Methoden der dynamischen Gebäudesimulation entwickelt. Zunächst wird das methodische Vorgehen für die Entwicklung von typgebäudebezogenen Nutzenergiebedarfsprofilen für die Nachfrage nach Heizwärme und Trinkwarmwasser erläutert. Im zweiten Schritt werden diese Profile mit verschiedenen Wärmeerzeugermodellen gekoppelt, wobei deren Nennleistung, Speichervolumen und Betriebsweise vari ieren. Hierdurch kann auch der Bedarf des Wärmeerzeugers nach Brennstoff oder Strom in Abhängigkeit der Dimensionierung und der Systemregelung zeitschrittbezogen abgebildet werden. Daneben kann durch eine Kombination der vorsimulierten Profile auch der Wärmebedarf eines Quartiers effizient modelliert werden. In diesem Zusammenhang wird abschließend die Einbindung der Profile in ein solares Nahwärmenetzmodell demonstriert.
An overview of energy district tools in Europe and the importance of an equivalent heating reference temperature for district simulations
Authors: Dermentzis Georgios , Schnieders Jürgen , Pfluger Rainer , Pfeifer Domink , Feist Wolfgang , Ochs Fabian
Published: October 2017

The international building sector plays an important role on energy policy and reduction of CO2 emissions. The focus of energy conservation has started from building level and nowadays expands to district, city, region or national level. In this study, an overview, performed within the European project Sinfonia for preparation of a new district tool with focus on energy conservation, will be presented about existing district tools. Several aspects of the tools were included in the overview, such as focus, aim, analytical approach, methodology, geographical coverage, required input data, commercial/freeware, source code, language, tool status, organization/project developing the tool, and web link. The main components of energy district tools such as 3D geographical data, data for building features and properties, and simulation methods were also addressed.

Additionally, the issue of appropriate boundary conditions on urban energy analysis, such as user behaviour, will be discussed. A simulation study of a dwelling in various energy standards including different occupant scenarios was performed, and as a result, a formula was developed to estimate an equivalent heating reference temperature as a function of building envelope, living area, and outdoor temperature. Thus, the estimated equivalent heating reference temperature can be used as input in district energy simulations, instead of a constant set point value independent of the building.

The present study can serve as a basis for new or further development of tools trying to cover the gap and the limits of the existing ones.
Application of a novel prognostic invasive lesion index in ductal carcinoma in situ with minimal invasion of the breast
Authors: He Xiaofang , Ye Feng , Li Mei , Yu Ping , Xiao Xiangsheng , Tang Hailin , Xie Xiaoming
Published: October 2017

Multiple invasive foci has been shown to increase the risk of lymph node metastasis (LNM) in early breast cancer, but its prognostic implication remains unknown. We aimed to identify the prognostic value of the number of invasive foci in ductal carcinoma in situ with minimal invasion of the breast (DCIS‐MI), and further establish a prognostic invasive lesion index (ILI). A total of 193 patients with DCIS‐MI (the invasive component was up to 10 mm in diameter) were included. Univariate and multivariate analysis (logistic regression) were used to evaluate the predictive value of the number of invasive foci in LNM. The Kaplan–Meier curve was used for survival analysis. More than five invasive foci was an independent predictor for LNM (OR, 2.67, 95% CI, 1.12–6.33, P = 0.026), and associated with significantly shorter disease‐free survival (DFS) and overall survival (OS) compared with no more than five invasive foci (mean DFS 123.8 vs. 148.0 months, P = 0.002; and mean OS 133.5 vs. 151.4 months, P = 0.025). The ILI was established by the sum scores of the number of invasive foci and the invasive component size, having an optimal cut‐off point of 5.5 scores. The high‐ILI group (ILI >5 scores) had a higher incidence of LNM (23.6% vs. 6.9%) and worse prognosis than the low‐ILI group (ILI ≤5 scores). In conclusion, more than five invasive foci was an independent predictor for LNM and an unfavorable prognostic parameter. The ILI could potentially be used to predict survival prognosis in patients with DCIS‐MI.
Development and validation of a nomogram predicting the overall survival of stage IV breast cancer patients
Authors: Li Shunrong , Zhao Jianli , Zhu Liling , Su Fengxi , Chen Kai
Published: October 2017

This study aimed to develop a nomogram to predict the overall survival (OS) of stage IV breast cancer patients. We searched the National Cancer Database (NCDB) for stage IV breast cancer patients diagnosed between 2010 and 2013. Predictors of OS were identified and a nomogram was developed and validated using concordance index (C‐index), calibration plots, and risk group stratifications. A total of 7199 patients from the NCDB were included in the study. With a median follow‐up of 25.7 months, the 1‐year and 3‐year OS rates were 80.6% and 52.5%, respectively. Race, age, comorbidity status, T‐stage, grade, ER/PR/Her2 status, the presence of lung/liver/brain metastasis, surgery, radiotherapy, and chemotherapy were significantly associated with OS. The developed nomogram had a C‐index of 0.722 (95% CI 0.710–0.734) and 0.725 (95% CI 0.713–0.736) in the training and the validation cohorts, respectively. The predicted survival using the nomogram is well correlated with actual OS. The nomogram was able to stratify patients into different risk groups, among which the survival benefit of local therapy varied. We developed a nomogram to predict the overall survival of stage IV breast cancer patients. Prospectively designed studies with international collaborations are needed to further validate our nomogram.
Protonation‐Initiated Cyclization by a Class II Terpene Cyclase Assisted by Tunneling
Authors: Eriksson Adam , Kürten Charlotte , Syrén Per‐Olof
Published: October 2017

Terpenes represent one of the most diversified classes of natural products with potent biological activities. The key to the myriad of polycyclic terpene skeletons with crucial functions in organisms from all kingdoms of life are terpene cyclase enzymes. These biocatalysts enable stereospecific cyclization of relatively simple, linear, prefolded polyisoprenes by highly complex, partially concerted, electrophilic cyclization cascades that remain incompletely understood. Herein, additional mechanistic light is shed on terpene biosynthesis by kinetic studies in mixed H2O/D2O buffers of a class II bacterial ent‐copalyl diphosphate synthase. Mass spectrometry determination of the extent of deuterium incorporation in the bicyclic product, reminiscent of initial carbocation formation by protonation, resulted in a large kinetic isotope effect of up to seven. Kinetic analysis at different temperatures confirmed that the isotope effect was independent of temperature, which is consistent with hydrogen tunneling.
Nitric oxide synthase inhibitor L‐NAME affects Arabidopsis root growth, morphology, and microtubule organization
Authors: Krasylenko Yuliya A. , Yemets Alla I. , Blume Yaroslav B.
Published: October 2017

The presence of evolutionarily conserved NOS or NOS‐like enzymes in land plants different than those in animals is still unclear, despite their activity has been revealed in cytosol and some organelles. At the same time, the emerging evidence for the importance of L‐arginine‐dependent pathways of NO synthesis in plant cells is still accumulating. The aim of our study was to reveal physiological effects on growth and differentiation processes, and microtubular cytoskeleton organization of the competitive mammalian NO synthase inhibitor Nω‐nitro‐L‐arginine methylester (L‐NAME). Thus, the treatment of Arabidopsis with L‐NAME (50–1 mM) caused dose‐ and time‐dependent inhibition of primary roots growth. Moreover, the morphology of primary roots under the influence of L‐NAME also underwent changes. L‐NAME (>100 µM) induced the formation of novel over‐elongated root hairs in shortened elongation zone, while in higher concentrations (500 µM) it caused a slight swelling of epidermal cells in differentiation zone. L‐NAME also provoked microtubule reorganization in epidermal cells of different root growth zones. Thus, L‐NAME at concentrations of 50–1 mM induced cortical microtubules randomization and/or depolymerization in epidermal cells of the root apex, meristem, transition, elongation, and differentiation zones after 2 h of treatment. Disordered microtubules in trichoblasts could initiate the formation of actively elongating root hairs that reveals longitudinal microtubules ensuring their active growth at 24 h of treatment. Therefore, L‐NAME inhibits primary root growth, induces the differentiation processes in roots, reorganizes cortical microtubules in epidermal root cells suggesting the importance of L‐arginine‐dependent pathways of NO synthesis in plants.
Leptin differentially regulates endochondral ossification in tibial and vertebral epiphyseal plates
Authors: Li Xiaomiao , Shi Sheng , Chen Jianwei , Zhong Guibin , Li Xinfeng , Liu Zude
Published: October 2017

Longitudinal bone growth is governed by a complex network of endocrine signals including leptin. In mouse, leptin deficiency leads to distinct phenotypes in bones of the limb and spine, suggesting the appendicular and axial skeletons are subject to differential regulation by leptin. We established primary cultures for the chondrocytes from tibial and vertebral epiphyseal plates. Cellular proliferation and apoptosis were analyzed for the chondrocytes that had been treated with various concentrations of leptin. Crucial factors for chondrocyte proliferation and differentiation, such as BMP7 and Wnt3, were measured in the cells treated with leptin alone or in combination with pharmacological inhibitors of STAT and ERK signaling pathways. Primary culture of tibial epiphyseal plate chondrocytes has greater proliferating capability compared with that of vertebral epiphyseal plate chondrocytes. Leptin could promote the proliferation of tibial epiphyseal plate chondrocytes, while its effect on vertebral epiphyseal plate chondrocytes was inhibitory. Consistently, apoptosis is inhibited in tibial but promoted in vertebral epiphyseal plate chondrocytes by leptin. Importantly, leptin differentially modulates chondrogenic signaling pathways in tibial and vertebral epiphyseal chondrocytes through STAT and ERK pathways. Leptin differentially regulates chondrogenic proliferation and differentiation in appendicular and axial regions of the skeletons. The signaling pathways in these two regions are also distinct and subject to differential regulation by leptin through the STAT pathway in tibial epiphyseal plate chondrocytes but through the ERK pathway in vertebral epiphyseal plate chondrocytes. Therefore, the regulation of leptin is multi‐faceted in the distinct anatomical regions of the skeleton. Knowledge gained from this system will provide insights into the pathophysiological causes for the diseases related to bone development and metabolism.
Concomitant occurrence of primary hyperparathyroidism (PHPT) due to mediastinal parathyroid adenoma and sublingual thyroid gland: the role of parathyroid technetium‐99m‐MIBI scintigraphy
Authors: Choukry Sara , Benouhoud Jaafar , Cherkaoui Salhi Ghofrane , Taleb Sara , Guensi Amal , Choukry Karim
Published: October 2017

Key Clinical Message

The concomitant appearance of a sublingual thyroid and primary hyperparathyroidism due to parathyroid mediastinal adenoma is not common. This co‐occurrence can lead to a misdiagnosis by morphological imaging methods alone. This case emphasizes the role of 99mTc‐MIBI scintigraphy in the detection of parathyroid ectopic adenoma in a patient with an ectopic thyroid gland. This more accurate location of parathyroid scintigraphy is of great benefit to the surgeon for surgical excision.
Pauling Electronegativity On/Off Effects Assessed by 13C and 29Si NMR Spectroscopic Analysis
Authors: Benedetti Michele , De Castro Federica , Fanizzi Francesco P.
Published: October 2017

In carbon and silicon tetrahalide compounds, the experimental 13C and 29Si NMR chemical‐shift values are known to increase or decrease on increasing the overall sum of the ionic radii of the bonded halides Σ(rh) (normal and inverse halogen dependence (NHD and IHD, respectively)). Herein, we extrapolate the main factors responsible for such NMR chemical shifts. Intriguingly, we found a characteristic value for the overall sum of the Pauling electronegativities of the bonded halides Σ(χh), which works as a triggering factor to determine the transition from the NHD to IHD. Below this Σ(χh) value, the chemical shift of the central atom was strictly related to only the Σ(rh) value, thus producing a NHD trend. Conversely, above this value, the chemical shift of the central atom was dependent on both the Σ(rh) and Σ(χh) values, thus producing a IHD trend. A simple model, in which the effect of the Σ(χh) value on 13C and 29Si NMR chemical shifts is related to an apparent increase in the Σ(rh) value, is deduced.
Metallic Ni3P/Ni Co‐Catalyst To Enhance Photocatalytic Hydrogen Evolution
Authors: Zhao Jun Jie , Liu Peng Fei , Wang Yu Lei , Li Yu Hang , Zu Meng Yang , Wang Chong Wu , Wang Xue Lu , Fang Li Jun , Zeng Hui Dan , Yang Hua Gui
Published: October 2017

Metallic Ni3P/Ni can be used as a co‐catalyst to replace noble metal Pt for efficient photocatalytic hydrogen evolution, due to its excellent trapping‐electron ability. The applications of metallic Ni3P/Ni co‐catalyst on CdS, Zn0.5Cd0.5S, TiO2 (Degussa P25) and g‐C3N4 are further confirmed, indicating its versatile applicability nature like Pt.
Pseudocyclic Arylbenziodoxaboroles: Efficient Benzyne Precursors Triggered by Water at Room Temperature
Authors: Yoshimura Akira , Fuchs Jonathan M. , Middleton Kyle R. , Maskaev Andrey V. , Rohde Gregory T. , Saito Akio , Postnikov Pavel S. , Yusubov Mekhman S. , Nemykin Victor N. , Zhdankin Viktor V.
Published: October 2017

New organohypervalent iodine compounds, arylbenziodoxaborole triflates, were prepared from 1‐acetoxybenziodoxaboroles and arenes by treatment with trifluoromethanesulfonic acid under mild conditions. Single crystal X‐ray crystallography of these compounds revealed a pseudocyclic structure with a short intramolecular interaction of 2.698 to 2.717 Å between oxygen and iodine in the benziodoxaborole ring. These new pseudocyclic aryliodonium salts readily generate aryne intermediates upon treatment with water at room temperature. The generated aryne intermediates react with various substrates to give the corresponding aryne adducts in moderate to good yields. Furthermore, the new benzyne precursors can also work as arylating reagents towards aromatic rings. The aryne intermediates generated from arylbenziodoxaborole triflates selectively react with tert‐butyl phenol forming products of ortho arylation in moderate yields.
Click Chemistry for Analysis of Cell Proliferation in Flow Cytometry
Authors: Clarke Scott T. , Calderon Veronica , Bradford Jolene A.
Published: October 2017

The measurement of cellular proliferation is fundamental to the assessment of cellular health, genotoxicity, and the evaluation of drug efficacy. Labeling, detection, and quantification of cells in the synthesis phase of cell cycle progression are not only important for characterizing basic biology, but also in defining cellular responses to drug treatments. Changes in DNA replication during S‐phase can provide valuable insights into mechanisms of cell growth, cell cycle kinetics, and cytotoxicity. A common method for detection of cell proliferation is the incorporation of a thymidine analog during DNA synthesis. This chapter presents a pulse labeling method using the thymidine analog, 5‐ethynyl‐2′‐deoxyuridine (EdU), with subsequent detection by click chemistry. EdU detection using click chemistry is bio‐orthogonal to most living systems and does not non‐specifically label other biomolecules. Live cells are first pulsed with EdU. After antibody labeling cell surface markers, fixation, and permeabilization, the incorporated EdU is covalently labeled using click chemistry thereby identifying proliferating cells. Improvements in click chemistry allow for labeling in the presence of fluorescent proteins and phycobiliproteins without quenching due to copper. Measuring DNA replication during cell cycle progression has cell health applications in flow cytometry, fluorescence microscopy, and high content imaging. This protocol has been developed and optimized for research use only and is not suitable for use in diagnostic procedures. © 2017 by John Wiley & Sons, Inc.
CyTOF Measurement of Immunocompetence Across Major Immune Cell Types
Authors: Subrahmanyam Priyanka B. , Maecker Holden T.
Published: October 2017

The central role of the immune system is becoming appreciated in a wide variety of diseases. Cancer immunotherapy is one area that has yielded much recent success, although not all patients benefit equally. At the same time, recent studies have highlighted the heterogeneity of the human immune system. Despite this heterogeneity, we do not routinely measure immune competence in clinical practice, and there are no consensus assays of healthy immune function. Using mass cytometry (CyTOF), we can simultaneously detect ∼40 markers to identify various cell subsets and determine their function by the expression of cytokines, cytotoxicity, and activation markers. This can help assess ‘immunocompetence’ and facilitate better implementation of immunotherapies, both in specific disease settings and perhaps eventually as a prognostic tool in healthy subjects. Here we introduce the concepts behind this assay and provide a protocol that we have successfully implemented to identify possible predictive biomarkers of immunotherapy outcome. © 2017 by John Wiley & Sons, Inc.
Analysis of Cellular DNA Content by Flow Cytometry
Authors: Darzynkiewicz Zbigniew , Huang Xuan , Zhao Hong
Published: October 2017

Cellular DNA content can be measured by flow cytometry with the aim of : (1) revealing cell distribution within the major phases of the cell cycle, (2) estimating frequency of apoptotic cells with fractional DNA content, and/or (3) disclosing DNA ploidy of the measured cell population. In this unit, simple and universally applicable methods for staining fixed cells are presented, as are methods that utilize detergents and/or proteolytic treatment to permeabilize cells and make DNA accessible to fluorochrome. Additionally, supravital cell staining with Hoechst 33342, which is primarily used for sorting live cells based on DNA‐content differences for their subsequent culturing, is described. Also presented are methods for staining cell nuclei isolated from paraffin‐embedded tissues. Available algorithms are listed for deconvolution of DNA‐content‐frequency histograms to estimate percentage of cells in major phases of the cell cycle and frequency of apoptotic cells with fractional DNA content. © 2017 by John Wiley & Sons, Inc.
Staining of Frozen and Formalin‐Fixed, Paraffin‐Embedded Tissues with Metal‐Labeled Antibodies for Imaging Mass Cytometry Analysis
Authors: Chang Qing , Ornatsky Olga , Hedley David
Published: October 2017

This unit describes protocols for labeling tissue sections using combinations of metal‐tagged antibodies and an iridium‐containing DNA intercalator for analysis by imaging mass cytometry. Imaging mass cytometry (IMC) allows the labeling of up to 40 individual markers simultaneously using antibody cocktails. We discuss labeling of both cryostat sections and sections from formalin‐fixed, paraffin‐embedded (FFPE) tissue blocks. The protocols are similar to those used for optical microscopy techniques, while allowing much higher complexity of analysis. © 2017 by John Wiley & Sons, Inc.
A Detailed Protocol for Subcellular RNA Sequencing (subRNA‐seq)
Authors: Mayer Andreas , Churchman L. Stirling
Published: October 2017

In eukaryotic cells, RNAs at various maturation and processing levels are distributed across cellular compartments. The standard approach to determine transcript abundance and identity in vivo is RNA sequencing (RNA‐seq). RNA‐seq relies on RNA isolation from whole‐cell lysates and thus mainly captures fully processed, stable, and more abundant cytoplasmic RNAs over nascent, unstable, and nuclear RNAs. Here, we provide a step‐by‐step protocol for subcellular RNA‐seq (subRNA‐seq). subRNA‐seq allows the quantitative measurement of RNA polymerase II–generated RNAs from the chromatin, nucleoplasm, and cytoplasm of mammalian cells. This approach relies on cell fractionation prior to RNA isolation and sequencing library preparation. High‐throughput sequencing of the subcellular RNAs can then be used to reveal the identity, abundance, and subcellular distribution of transcripts, thus providing insights into RNA processing and maturation. Deep sequencing of the chromatin‐associated RNAs further offers the opportunity to study nascent RNAs. Subcellular RNA‐seq libraries are obtained within 5 days. © 2017 by John Wiley & Sons, Inc.
Heterogeneity and scaling of photosynthesis, respiration, and nitrogen uptake in three Atlantic Rainforest streams
Authors: Tromboni Flavia , Dodds Walter K. , Neres‐Lima Vinicius , Zandonà Eugenia , Moulton Timothy P.
Published: October 2017

Leaves, epilithon, macrophytes, and fine benthic organic material are central ecosystem compartments to food webs and mediate nutrient fluxes in streams. Most estimates of gross primary production (GPP) and ecosystem respiration (ER) are made at a reach scale, averaging across compartments. Thus, there is little information on how individual compartments contribute to and scale up to whole‐stream estimates across watersheds. We compared estimates of GPP, ER, and nitrogen (N) uptake of individual ecosystem compartments (dm) and stream reaches (~100 m) in three sizes of streams in a preserved Atlantic Rainforest watershed. The smallest stream had dense forest canopy cover, whereas the largest was more open. We measured substratum‐specific rates of GPP and ER, as well as ammonium and nitrate 15N uptake in recirculating chambers. We compared these decimeter‐scale measurements to whole‐stream estimates, using single‐station dissolved oxygen (GPP and ER) and pulsed N uptake methods. Epilithon and macrophytes (when present) were the dominant GPP and N uptake compartments in open‐canopy sites, and leaves contributed strongly to ER at all sites, even though they covered <3 percent of the stream bottom. Ammonium and nitrate uptake per unit N content varied significantly among substrata and streams. Upscaled inorganic N uptake per unit area was greater when macrophytes were present. Chamber measurements overestimated metabolic rates in the larger streams, but not in the smallest one. The smallest transient storage zone streams were more active than the biggest one, and this influenced the mismatch between whole‐stream and chamber nutrient uptake estimates. We conclude that scaling to the whole watershed requires information on location in the watershed (e.g., where canopy cover is dense), rates of individual compartments, and reach‐specific hydrodynamic information as influenced by large‐scale geomorphic details (i.e., the size and activity of the transient storage zones).
Rationale and study design of intravenous loop diuretic administration in acute heart failure: DIUR‐AHF
Authors: Palazzuoli Alberto , Ruocco Gaetano , Vescovo Giorgio , Valle Roberto , Di Somma Salvatore , Nuti Ranuccio
Published: October 2017

Aims

Although loop diuretics are the most commonly used drugs in acute heart failure (AHF) treatment, their short‐term and long‐term effects are relatively unknown. The significance of worsening renal function occurrence during intravenous treatment is not clear enough. This trial aims to clarify all these features and contemplate whether continuous infusion is better than an intermittent strategy in terms of decongestion efficacy, diuretic efficiency, renal function, and long‐term prognosis.

Methods and results

This is a prospective, multicentre, randomized study that compares continuous infusion to intermittent infusion and a low vs. high diuretic dose of furosemide in patients with a diagnosis of acute heart failure, BNP ≥ 100 pg/mL, and specific chest X‐ray signs. Randomization criteria have been established at a 1:1 ratio using a computer‐generated scheme of either twice‐daily bolus injection or continuous infusion for a time period ranging from 72 to 120 h. The initial dose will be 80 mg/day of intravenous furosemide and, in the case of poor response, will be doubled using an escalation algorithm. A high diuretic dose is defined as a furosemide daily amount >120 mg/day respectively.

Conclusions

Continuous and high dose groups could reveal a more intensive diuresis and a greater decongestion with respect to intermittent and low dose groups; high dose and poor loop diuretic efficiency should be related to increased diuretic resistance, renal dysfunction occurrence, and greater congestion status. Poor diuretic response will be associated with less decongestion and an adverse prognosis.
Similar clinical benefits from below‐target and target dose enalapril in patients with heart failure in the SOLVD Treatment trial
Authors: Lam Phillip H. , Dooley Daniel J. , Fonarow Gregg C. , Butler Javed , Bhatt Deepak L. , Filippatos Gerasimos S. , Deedwania Prakash , Forman Daniel E. , White Michel , Fletcher Ross D. , Arundel Cherinne , Blackman Marc R. , Adamopoulos Chris , Kanonidis Ioannis E. , Aban Inmaculada B. , Patel Kanan , Aronow Wilbert S. , Allman Richard M. , Anker Stefan D. , Pitt Bertram , Ahmed Ali
Published: October 2017

Aims

To examine associations of below‐target and target dose of enalapril, an angiotensin‐converting enzyme (ACE) inhibitor, with outcomes in patients with heart failure and reduced ejection fraction (HFrEF) in the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial.

Methods and results

Two thousand five hundred and sixty‐nine patients with HFrEF (ejection fraction ≤35%) were randomized to below‐target (5–10 mg/day) dose placebo (n = 1284) or enalapril (n = 1285). One month post‐randomization, blind up‐titration to target (20 mg/day) dose was attempted for both study drugs in 2458 patients. Among the 1444 patients who achieved dose up‐titration (placebo, n = 748; enalapril, n = 696; mean dose for both groups, 20.0 mg/day), target dose enalapril (vs. target dose placebo) was associated with a 9% absolute lower risk of the combined endpoint of heart failure hospitalization or all‐cause mortality [adjusted hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.60–0.81; P < 0.001] during 4 years of follow‐up. Among the 1014 patients who could not achieve target dose (placebo, n = 486; enalapril, n = 528; mean dose for both groups, 8.8 mg/day), below‐target dose enalapril (vs. below‐target dose placebo) was associated with a 12% absolute lower risk of the combined endpoint of heart failure hospitalization or all‐cause mortality (adjusted HR 0.68; 95% CI 0.57–0.81; P < 0.001). Among the 1224 patients receiving enalapril, target (vs. below‐target) dose had no association with the combined endpoint of heart failure hospitalization or all‐cause mortality (adjusted HR 1.04; 95% CI 0.87–1.23; P = 0.695).

Conclusion

In patients with HFrEF, the clinical benefits of ACE inhibitors appear to be similar at both below‐target and target doses.
Carbazole as Linker for Dinuclear Gadolinium‐Based MRI Contrast Agents
Authors: Mousavi Bibimaryam , Chauvin Anne‐Sophie , Moriggi Loïck , Helm Lothar
Published: October 2017

Ligands able to complex two gadolinium ions have been synthesized and characterized in view of the ability of the complexes to increase the spin relaxation of water protons. All ligands are based on the heptadentate diethylenetriaminetetraacetic acid (DTTA) chelator and carbazole as a rigid linker. Depending on the derivatization on the nitrogen atom of the five‐membered ring, the compounds form small aggregates in aqueous solution, self‐assemble to form micelles or bind to human serum albumin. In all cases, this leads to a marked increase in 1H relaxivity at nuclear Larmor frequencies between 20 and 60 MHz. Water exchange on the gadolinium ions as measured by 17O NMR relaxation is fast enough not to limit relaxivity. 1H nuclear magnetic relaxation dispersion profiles were also measured and analyzed using Solomon–Bloembergen–Morgan theory including Lipari–Szabo treatment to include internal motion or anisotropic rotation.
Geological documentation – Conditions, status quo and future development
Authors: Weichenberger Franz Peter , Pischinger Gerald
Published: October 2017

The construction of subsurface underground structures poses a special challenge for the involved project team. The goal of geological documentation is to record the conditions as precisely as possible and provide support to the entire team based on this information. To this end, the situation is recorded during the advance, sketches are drawn, digital photos are taken and measurements are made. It has now become standard practice to store and evaluate the data obtained digitally. For this purpose powerful computerized information systems have been developed to store and evaluate large amounts of data. Geological observations in underground construction are almost exclusively spatial information and are recorded in three dimensions. In addition to the types of rocks encountered, the positional relationships of the geological bodies to each other and the discontinuity system of the rock mass have a great influence on the stability of the cavity. Future developments will be concerned with the integration of the geological data into BIM systems. Compared to present GIS techniques this will enable a more effcient aggregation with other tunnel construction data. Mobile applications will make it possible to record observations directly in digital form, thus avoiding redundancies.
An innovative method of upgrading old rail tunnels under continued operation – Example Rekawinkler‐ and Kleiner Dürreberg Tunnel
Authors: Seywald Christian , Helmberger Albert , Matt Robert
Published: October 2017

The ÖBB‐Infrastruktur AG operates and maintains 246 tunnels and similar structures with an overall length of approx. 250 km. Nearly 150 of these structures are more than 100 years old, 35 of them are over 150 years old. Ageing processes, the impact of train traffic, ground conditions and environmental conditions are causing progressive damage to the tunnel linings, which – in order to maintain safe railway operation – requires ongoing maintenance procedures. Those procedures are carried out under a range of restrictions concerning availability, which is one of the most important principles at the ÖBB after safety. In order to obtain continuous availability of the facility, new methods of refurbishment were developed for the two double‐track tunnels Rekawinkler Tunnel and Kleine Dürreberg. The described methods enabled extensive repair works of the tunnels, mostly with uninterrupted train traffic on the second track.
Integration of reflection seismic data into the documentation during the construction of the Brenner Base Tunnel
Authors: Schwarz Christian , Schierl Heimo
Published: October 2017

The 64 km long Brenner Base Tunnel will be the longest railway tunnel in the world when complete. As part of this mega project, an exploratory tunnel is currently under construction with a tunnel boring machine (∅ 8 m). Even though a geological model along the tunnel route was generated beforehand from the results of geological field mapping and deep drilling campaigns from the surface, some uncertainties persist due to the high overburden of up to 1,300 m. In particular, several fault systems intersect the tunnel route, but their position and orientation is uncertain. The excavation work is being documented with geological and geotechnical data, continuously updating the current geological model. Continuous seismic prediction measurements are integrated into this revision process. The aim is the detection, location and characterization of (sub‐)perpendicular to (sub‐)parallel fault zones ahead and to the side of the tunnel, based on the principle of body wave propagation. In a case study of a seismic campaign, the smooth integration of the acquisition into the regular advance is presented and the obtained 3D seismic models are compared to the geological documentation of the site geologists. It will be shown how the seismic analysis gives an added value for the advance and how it benefits the geological forecast for the forthcoming main tunnels.
Headrace system of HPP Obervermuntwerk II – Geotechnical design and experience
Authors: Dich Christopher , Barwart Christian
Published: October 2017

The Vorarlberger Illwerke AG is constructing the 360 MW Obervermuntwerk II pumped storage power. The project area is located in the upper Montafon, Austria. The head between the elevations of the ”Silvrettaspeicher“ and ”Vermuntspeicher“ reservoirs will be exploited for production of electric energy. The Obervermuntwerk II is designed as a pumped storage plant with two highly flexible turbine/pump sets to operate the so called ”hydraulic short‐circuit“. At maximum gross head of 317 m and a maximum design discharge of Q = 150 m3/s, an electric power of 360 MW will be generated, which is equal to the pumping power. Upon completion, it will be the second largest pumped storage power plant of the Vorarlberger Illwerke AG. The construction of the approx. 500 million € project began in May 2014 and is expected to start operating in 2018. The paper describes the underground waterway, its geotechnical design, the implementation concept and the construction experience gained up to June 2017.
Compensation grouting – Balance between asset protection and collateral damage through the example of Crossrail C510
Authors: Stärk Alfred , Pujol Roser Soler , Hill Nigel , Kettle Clif T.
Published: October 2017

Crossrail, a new 120 km long railway line, is currently the largest infrastructure project in Europe with a volume of about GBP 15 billion. Contract C510 includes the new Liverpool Street station in the City of London using the sprayed concrete lining method. The station tunnels were excavated in close proximity to a dense network of existing tunnels. The multi‐storey office buildings on the densely built up surface include some listed buildings. The aim of compensation grouting in the first place was to avoid settlement due to tunnel construction altogether, or at least minimise the impact within defined limits. Remediation of settlement which occurred regardless was only anticipated in extraordinary circumstances. This paper highlights the difficulties of balancing the desired control of settlement by means of compensation grouting against adverse effects on adjacent structures. The paper closes with a description of how the seemingly impossible lifting of one column eventually worked by localised grouting.