bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing Conformational Variation in Luminescent Dinuclear Gold(I) N‐Heterocyclic Carbene Complexes
Authors: Pell Thomas P. , Stringer Bradley D. , Tubaro Cristina , Hogan Conor F. , Wilson David J. D. , Barnard Peter J.
Published: June 2017

A series of six dinuclear AuI complexes bearing arene‐bridged bidentate imidazolylidene (N‐heterocyclic carbene, NHC) ligands have been synthesized and characterized. The ligand arene linkers (benzene, pyridine, pyrazine) and NHC‐wingtip R‐groups (methyl, benzyl) were modified to investigate the influence of these groups on the preference for two distinct conformational isomeric forms. These two conformations differ in their Au···Au distances; an open form with an Au···Au separation of ca. 7 Å and a twisted conformation with a short Au···Au distance of ca. 3 Å. Five of the complexes were structurally characterized using X‐ray crystallography. Photophysical studies on the complex with a pyridyl linker group and benzyl wingtip groups showed that the twisted conformation resulted in a low‐energy (LE) photoluminescence emission that is associated with the intermolecular aurophilic interaction. In contrast, no room temperature (r.t.) photoluminescence was observed for the open conformation in the solid state, while a high‐energy (HE) emission was observed at 77 K. The pyridyl linked complexes were non‐emissive in solution at room temp., but upon freezing to form a glassy matrix at 77 K, dual HE and LE emissions were observed that closely match the solid‐state spectra for open and twisted complexes, respectively. These observations, in combination with a thorough theoretical investigation, provide important insights into the conformational behavior of complexes of this type. The use of low temperature frozen glasses to trap individual components of conformationally diverse samples for photoluminescence investigations represents a novel approach to study the dynamic and conformational behavior of dinuclear AuI complexes in solution.
An Efficient Homogenized Ruthenium(II) Pincer Complex for N‐Monoalkylation of Amines with Alcohols
Authors: Yang Fa‐Liu , Wang Ying‐Hui , Ni Yong‐Feng , Gao Xiang , Song Bing , Zhu Xinju , Hao Xin‐Qi
Published: June 2017

An ionic 2,6‐bis(imidazo[1,2‐α]pyridin‐2‐yl)pyridine‐based N^N^N pincer ruthenium(II) complex exhibited high efficiency in the C–N bond formation between amines and alcohols by the “borrowing hydrogen” (BH) or “hydrogen autotransfer” (HA) concept. The synthetic protocol selectively generated monoalkylated amines without formation of tertiary amines during the reaction. The unique selectivity enabled the formation of symmetrically and asymmetrically substituted diamines. This methodology features several advantages including a low catalyst loading (as low as 0.5 mol‐%), a short reaction time (as short as 2 h), and excellent N‐monoalkylation selectivity.
Capillary electrophoresis and nanomaterials – Part I: Capillary electrophoresis of nanomaterials
Authors: Adam Vojtech , Vaculovicova Marketa
Published: June 2017

Nanomaterials are in analytical science used for a broad range of purposes, covering the area of sample pretreatment as well as separation, detection, and identification of target molecules. This part of the review covers capillary electrophoresis (CE) of nanomaterials and focuses on the application of CE as a method for characterization used during nanomaterial synthesis and modification as well as the monitoring of their properties and interactions with other molecules. The heterogeneity of the nanomaterial family is extremely large. Depending on different definitions of the term Nanomaterial/Nanoparticle, the group may cover metal and polymeric nanoparticles, carbon nanomaterials, liposomes and even dendrimers. Moreover, these nanomaterials are usually subjected to some kind of surface modification or functionalization, which broadens the diversity even more. Not only for purposes of verification of nanomaterial synthesis and batch‐to‐batch quality check, but also for determination the polydispersity and for functionality characterization on the nanoparticle surface, has CE offered very beneficial capabilities. Finally, the monitoring of interactions between nanomaterials and other (bio)molecules is easily performed by some kind of capillary electromigration technique.
Evaluating morphological estimates of the aerodynamic roughness of debris covered glacier ice
Authors: Quincey Duncan , Smith Mark , Rounce David , Ross Andrew , King Owen , Watson Cameron
Published: June 2017

Aerodynamic roughness length (z0), the height above the ground surface at which the extrapolated horizontal wind velocity profile drops to zero, is one of the most poorly parameterised elements of the glacier surface energy balance equation. Microtopographic methods for estimating z0 have become prominent in the literature in recent years, but are rarely validated against independent measures and are yet to be comprehensively analysed for scale or data resolution dependency. Here, we present the results of a field investigation conducted on the debris covered Khumbu Glacier during the post‐monsoon season of 2015. We focus on two sites. The first is characterised by gravels and cobbles supported by a fine sandy matrix. The second comprises cobbles and boulders separated by voids. Vertical profiles of wind speed recorded by a tower comprising five cup anemometers and deployed over both sites enable us to derive measurements of aerodynamic roughness that reflect their observed surface characteristics (0.0184 m and 0.0243 m, respectively). At the second site, z0 also varied through time following snowfall (0.0055 m) and during its subsequent melt (0.0129 m), showing the importance of fine resolution topography for near‐surface airflow. To compare the wind profile data with microtopographic methods, we conducted structure from motion multi‐view stereo (SfM‐MVS) surveys across each patch and calculated z0 using three previously published approaches. The fully three‐dimensional cloud‐based approach is shown to be most stable across different scales and these z0 values are most correct in relative order when compared with the wind tower data. Popular profile‐based methods perform less well providing highly variable values across different scales and when using data of differing resolution. These findings hold relevance for all studies using microtopographic methods to estimate aerodynamic roughness lengths, including those in non‐glacial settings. Copyright © 2017 John Wiley & Sons, Ltd.
Partial deletion of the ALK gene in ALK‐positive anaplastic large cell lymphoma
Authors: Fukuhara Suguru , Nomoto Junko , Kim Sung‐Won , Taniguchi Hirokazu , Miyagi Maeshima Akiko , Tobinai Kensei , Kobayashi Yukio
Published: June 2017

Anaplastic lymphoma kinase (ALK) protein is an orphan receptor tyrosine kinase that is constitutively activated by aberrant translocations of the ALK gene in anaplastic large cell lymphoma, ALK‐positive and several other cancers. Additionally, aberrant mutation and amplification of the ALK gene, resulting in ALK kinase activation, were detected mainly in neuroblastoma. Recently, truncated ALK protein was also reported in neuroblastoma. Here, we describe a novel truncated form of the ALK transcript with in‐frame skipping through exons 2 to 17 (ALKΔ2‐17) in anaplastic large cell lymphoma, ALK‐positive. The ALKΔ2‐17 showed ligand‐independent deregulated phosphorylation that initiated strong STAT3 signalling in NIH3T3 cells. The ALKΔ2‐17–transduced NIH3T3 cells showed oncogenic potential in a colony formation assay. Our data indicate that the aberrant deletion of the ALK gene might be oncogenic, providing a novel insight into the oncogenic role of the ALK pathway.
Mediating Emotive Empathy With Informational Text: Three Students’ Think‐Aloud Protocols ofGettysburg: The Graphic Novel
Authors: Chisholm James S. , Shelton Ashley L. , Sheffield Caroline C.
Published: June 2017

Although the popularity and use of graphic novels in literacy instruction has increased in the last decade, few sustained analyses have examined adolescents’ reading processes with informational texts in social studies classrooms. Recent research that has foregrounded visual, emotional, and embodied textual responses situates this qualitative study, in which three eighth‐grade students learned about the graphic novel format, responded in writing to interpretive prompts, and thought aloud during their reading ofGettysburg: A Graphic Novelby C.M. Butzer. Analyses of students’ responses to the multimodal text revealed how constructing inferences between visual and linguistic sign systems mediated their emotive empathy—a central, if limited, component of historical empathy.
Assessment of the inhibitory effects and molecular docking of some sulfonamides on human serum paraoxonase 1
Authors: Alim Zuhal , Kilic Deryanur , Koksal Zeynep , Beydemir Sukru , Ozdemir Hasan
Published: June 2017

Paraoxonase‐1 (PON1) is an organophosphate hydrolyzer and antiatherogenic enzyme. Due to the PON1's crucial functions, inhibitors and activators of PON1 must be known for pharmacological applications. In this study, we investigated the in vitro effects of some sulfonamides compounds on human serum PON1 (hPON1). For this aim, we purified the hPON1 from human serum with high specific activity by using simple chromatographic methods, and after the purification processes, we investigated in vitro interactions between the enzyme and some sulfonamides (2‐amino‐5‐methyl‐1,3‐benzenedisulfonamide, 2‐chloro‐4‐sülfamoilaniline, 4‐amino‐3‐methylbenzenesulfanilamide, sulfisoxazole, sulfisomidine, and 5‐amino‐2‐methylbenzenesulfonamide). IC50, Ki values, and inhibition types were calculated for each sulfonamide. 2‐amino‐5‐methyl‐1,3‐benzenedisulfonamide and 2‐chloro‐4‐sülfamoilaniline exhibited noncompetitive inhibition effect, whereas 4‐amino‐3‐methylbenzenesulfanilamide, sulfisoxazole, and sulfisomidine exhibited mixed type inhibition. On the other hand, 5‐amino‐2‐methylbenzenesulfonamide showed competitive inhibition and so molecular docking studies were performed for this compound in order to assess the probable binding mechanism into the active site of hPON1.
In vitro antioxidant and cytoprotective properties of Maillard reaction products from phloridzin‐amino acid model systems
Authors: Han Linna , Li Feng , Yu Qijian , Li Dapeng
Published: June 2017

BACKGROUND

The aim of this study was to investigate in vitro antioxidant activities and cytoprotective effect of Maillard reaction products (MRPs) from phloridzin (Pz)‐amino acid model systems. Their structures were also characterised by Fourier transform‐infrared spectroscopy (FTIR).

RESULTS

MRPs were prepared from the Pz‐methionine (Met), Pz‐lysine (Lys), Pz‐isoleucine (Ile), Pz‐histidine (His) or Pz‐glutamic acid (Glu) model system. The Pz‐Lys MRPs, rich in antioxidant potency, were subjected to ultrafiltration to yield four MRPs fractions with different molecular weights (Mw). The fraction with Mw 30–50 kDa had significantly (P < 0.05) higher antioxidant activity than other fractions. Moreover, it significantly (P < 0.05) attenuated the 2,2′‐azobis(2‐methylpropionamidine) dihydrochloride (AAPH)‐elicited decrease in cell viability in HepG2 cells in a concentration‐dependent manner. FTIR analysis indicated that the fraction with Mw 30–50 kDa had the strong stretching vibration for the OH, NH, CH, CO and CC groups, suggesting the formation of intermediate MRPs during Maillard reaction.

CONCLUSION

The results obtained in this study may provide some basis for the purported health‐promoting effects of MRPs and their potential application as antioxidant agents in food industry. Also, it is important for our understanding of the variation of bioactive substances in food during thermal processing. © 2017 Society of Chemical Industry
Effects of feeding a Moringa oleifera rachis and twig preparation to dairy cows on their milk production and fatty acid composition, and plasma antioxidants
Authors: Zhang Tingting , Si Bingwen , Deng Kaidong , Tu Yan , Zhou Chaolong , Diao Qiyu
Published: June 2017

BACKGROUND

We determined how supplementing the diet of lactating, multiparous Holstein dairy cows with a preparation of Moringa oleifera rachises and twigs affected their milk production and quality and the levels of plasma antioxidants.

RESULTS

We found that milk yield increased in cows receiving the 6% (w/w) moringa supplement compared with that of the control. Addition of the moringa supplement increased the concentration of milk fat and decreased the somatic cell count in the milk. However, protein, glucose and total solid and urea nitrogen concentrations in the milk were the same for all treatments. The concentration of glutathione peroxidase increased for cows fed the moringa supplement compared with the control. The percentages of total unsaturated fatty acids, mono‐unsaturated fatty acids, and polyunsaturated fatty acids including n‐3 polyunsaturated fatty acid increased in the milk of cows fed the moringa supplement compared with those of the controls.

CONCLUSION

Addition of the moringa supplement into the diet of lactating multiparous cows improved milk production and health status and modified milk fatty acid profile positively. The results suggested that moringa supplement could be used as a diet supplement for producing high quality and healthier milk. © 2017 Society of Chemical Industry
Determination of polychlorinated dibenzo‐p‐dioxins and polychlorinated dibenzofurans, and dioxin‐like polychlorinated biphenyls in human serum using programmable‐temperature vaporization gas chromatography with high‐resolution mass spectrometry
Authors: Zhang Lei , Zhong Yuxin , Liu Xin , Bao Yan , Zhao Yunfeng , Wu Yongning , Cai Zongwei , Li Jingguang
Published: June 2017

The determination of polychlorinated dibenzo‐p‐dioxins and polychlorinated dibenzofurans, and dioxin‐like polychlorinated biphenyls in blood from a non‐occupational population is essential for the investigation of adverse health effects from these pollutants. In this study, a sensitive method based on programmable‐temperature vaporization with large‐volume injection coupled with gas chromatography with high‐resolution mass spectrometry was developed to determine these pollutants in 1–2 mL of human serum samples. Various key parameters of programmable‐temperature vaporization injector, including vent temperature, vent time, vent flow, transfer temperature and transfer time were optimized by factorial design. The accuracy and precision as well as applicability were assessed by determining polychlorinated dibenzo‐p‐dioxins, polychlorinated dibenzofurans, and dioxin‐like polychlorinated biphenyls in calibration standard solutions, standard reference materials and real human serum samples from non‐occupational population. The method detection limits of polychlorinated dibenzo‐p‐dioxins and polychlorinated dibenzofurans, and dioxin‐like polychlorinated biphenyls were 1.5–9.0 and 0.005–0.02 ng/kg wet weight, respectively. By comparing with typically splitless injection, the application of programmable‐temperature vaporization injector could effectively lead to higher detectable rate of polychlorinated dibenzo‐p‐dioxins and polychlorinated dibenzofurans, and dioxin‐like polychlorinated biphenyls in 1–2 mL of human serum samples.
Dual‐Crosslinking of Hyaluronic Acid–Calcium Phosphate Nanocomposite Hydrogels for Enhanced Mechanical Properties and Biological Performance
Authors: Jeong Seol‐Ha , Sun Jeong‐Yun , Kim Hyoun‐Ee
Published: June 2017

Herein, a facile approach for synthesizing mechanically enhanced nanocomposite hydrogels via a dual‐crosslinking process is described. Additional ionic crosslinking using various cations is introduced after an in situ precipitation process for hydroxyapatite immobilization in hyaluronic acid hydrogels (HAc–CaP). Ca2+, Ba2+, and Sr2+ ions exhibit the highest efficiencies in reinforcing the mechanical properties of HAc–CaP hydrogels. In addition, the dual‐crosslinked HAc–CaP hydrogels promote the biological responses of preosteoblast cells, which exhibit highly stretched shapes and greatly enhanced proliferation. Furthermore, the nanocomposite hydrogels achieve enhanced bioactivity by supporting osteogenic differentiation. Thus, enhancement on both the mechanical and biological properties of hyaluronic‐acid‐based nanocomposite hydrogels is achieved through this dual‐crosslinking process, extending the potential application of these materials to hard tissue engineering.
NMR spectroscopic conformational analysis of 4‐methylene‐cyclohexyl pivalate—The effect of sp2 hybridization
Authors: Kleinpeter Erich , Heydenreich Matthias , Koch Andreas , Krtitschka Angela , Krüger Tobias , Linker Torsten
Published: June 2017

The conformational equilibrium of the axial/equatorial conformers of 4‐methylene‐cyclohexyl pivalate is studied by dynamic NMR spectroscopy in a methylene chloride/freon mixture. At 153 K, the ring interconversion gets slow on the nuclear magnetic resonance timescale, the conformational equilibrium (−ΔG°) can be examined, and the barrier to ring interconversion (ΔG#) can be determined. The structural influence of sp2 hybridization on both ΔG° and ΔG# of the cyclohexyl moiety can be quantified.
Numerical analysis of the effect of natural microcracks on the supercritical CO2 fracturing crack network of shale rock based on bonded particle models
Authors: Peng Peihuo , Ju Yang , Wang Yongliang , Wang Shaoqin , Gao Feng
Published: June 2017

The problem of predicting the geometric structure of induced fractures is highly complex and significant in the fracturing stimulation of rock reservoirs. In the traditional continuous fracturing models, the mechanical properties of reservoir rock are input as macroscopic quantities. These models neglect the microcracks and discontinuous characteristics of rock, which are important factors influencing the geometric structure of the induced fractures. In this paper, we simulate supercritical CO2 fracturing based on the bonded particle model to investigate the effect of original natural microcracks on the induced‐fracture network distribution. The microcracks are simulated explicitly as broken bonds that form and coalesce into macroscopic fractures in the supercritical CO2 fracturing process. A calculation method for the distribution uniformity index (DUI) is proposed. The influence of the total number and DUI of initial microcracks on the mechanical properties of the rock sample is studied. The DUI of the induced fractures of supercritical CO2 fracturing and hydraulic fracturing for different DUIs of initial microcracks are compared, holding other conditions constant. The sensitivity of the DUI of the induced fractures to that of initial natural microcracks under different horizontal stress ratios is also probed. The numerical results indicate that the distribution of induced fractures of supercritical CO2 fracturing is more uniform than that of common hydraulic fracturing when the horizontal stress ratio is small.
Developing and validating a new nomogram for diagnosing bladder outlet obstruction in women
Authors: Solomon Eskinder , Yasmin Habiba , Duffy Megan , Rashid Tanwir , Akinluyi Emmanuel , Greenwell Tamsin J.
Published: June 2017

Objective

To develop and validate a nomogram for assessing bladder outlet obstruction (BOO) in women derived from concurrent Pdet.Qmax and Qmax based on radiographic evidence of increased urethral resistance.

Patients and Methods

Retrospective analysis of prospectively acquired video‐urodynamics and clinical data of 185 women (development cohort) was performed. The Pdet.Qmax were plotted against Qmax and cluster analysis was performed to determine an axis that best divided the definitively obstructed and unobstructed. Using data from a further 350 women (validation cohort), the sensitivity and specificity of the derived criterion was calculated. Finally, the data from both groups was pooled together and using binary logistic regression analysis, a nomogram was produced.

Results

Of the 535 patients in the two cohorts, (122 [22.8%]) demonstrated radiographic evidence of BOO. Cluster analysis identified the axis that best separates the radiographically obstructed and unobstructed as Pdet.Qmax = 2*Qmax. Using the data from the validation cohort, the sensitivity and specificity for this was calculated as 0.94 and 0.93, respectively. A nomogram, representing the probability of BOO for concurrent Pdet.Qmax and Qmax measurements was derived by pooling data from both cohorts. Alternatively, a female BOO index (BOOIf) may be calculated mathematically using the formula BOOIf = Pdet.Qmax − 2.2*Qmax, that is, BOOIf < 0, <10% probability of obstruction, BOOIf > 5 likely obstructed (50%) and If BOOIf > 18, obstruction almost certain (>90%).

Conclusion

A female BOO nomogram (the SG nomogram) with high sensitivity and specificity is proposed. The nomogram can be used to stratify the degree of BOO or assess response to treatment.
A multiphase DMOC‐based trajectory optimization method
Authors: Zhang Weizhong , Wang Dan , Inanc Tamer
Published: June 2017

Discrete mechanics and optimal control (DMOC) is a methodology that takes advantage of variational structure to solve certain optimal control problems for mechanical systems. This paper proposes to combine a multiphase strategy with the original DMOC method, resulting in a new multiphase DMOC (MDMOC) method and making optimal trajectory generation more efficient. The advantages of the proposed method are demonstrated mathematically, and in addition, a quadrotor, unmanned aerial vehicle, simulation example is presented to show its superiority over the DMOC method. Furthermore, to show its potential application, an arbitrarily chosen controller was used to track the desired trajectory generated by MDMOC. This new MDMOC methodology can also be applied to other mechanical systems such as mobile robots and underwater gliders.
Gapless point back surface field for the counter doping of large‐area interdigitated back contact solar cells using a blanket shadow mask implantation process
Authors: Kim Young‐Su , Mo Chanbin , Lee Doo Youl , Park Sung Chan , Kim Dongseop , Nam Junggyu , Yang JungYup , Suh Dongchul , Kim Hyun‐Jong , Park Hyomin , Park Se Jin , Kim Donghwan , Song Jungho , Lee Hae‐Seok , Park Sungeun , Kang Yoonmook
Published: June 2017

Gapless interdigitated back contact (IBC) solar cells were fabricated with phosphorous back surface field on a boron emitter, using an ion implantation process. Boron emitter (boron ion implantation) is counter doped by the phosphorus back surface field (BSF) (phosphorus ion implantation) without gap. The gapless process step between the emitter and BSF was compared to existing IBC solar cell with gaps between emitters and BSFs obtained using diffusion processes. We optimized the doping process in the phosphorous BSF and boron emitter region, and the implied Voc and contact resistance relationship of the phosphorous and boron implantation dose in the counter doped region was analyzed. We confirmed the shunt resistance of the gapless IBC solar cells and the possibility of shunt behavior in gapless IBC solar cells. The highly doped counter doped BSF led to a controlled junction breakdown at high reverse bias voltages of around 7.5 V. After the doping region was optimized with the counter doped BSF and emitter, a large‐area (5 inch pseudo square) gapless IBC solar cell with a power conversion efficiency of 22.9% was made.
Soluble polyimides containing 1,4:3,6‐dianhydro‐d‐glucidol and fluorinated units: Preparation, characterization, optical, and dielectric properties
Authors: Mi Zhiming , Liu Zhixiao , Tian Chengshuo , Zhao Xiaogang , Zhou Hongwei , Wang Daming , Chen Chunhai
Published: June 2017

Aiming to develop soluble and colorless polyimides, two novel diamines, 2,5‐bis(2‐trifluoromethyl‐4‐amino‐phenoxy)‐1,4:3,6‐dianhydrosorbitol (2a) and 2,5‐bis(2‐methyl‐4‐amino‐phenoxy)‐1,4:3,6‐dianhydrosorbitol (2b), were designed and synthesized by the reduction of corresponding dinitro monomer which was obtained via solvent‐free melt heating method. Polyimides (PI–(1–5)) containing 1,4:3,6‐dianhydro‐d‐glucidol fragments were prepared from 2a and five kinds of common dianhydrides and PI–6 was synthesized from 2b and 4,4′‐(hexafluoroisopropylidene)‐diphthalic anhydride (6FDA) via a two‐step thermal imidization. All the polyimides were readily soluble in common polar solvents and could afford flexible, tough, and transparent films with transparency as high as 87% at 450 nm. Meanwhile, PI–(1–6) exhibited unexpectedly low dielectric constants of 2.02–2.52 at 1 MHz. In addition, analogs PI–7 derived from 2,5‐bis(4‐amino‐phenoxy)‐1,4:3,6‐dianhydrosorbitol (2c) and 6FDA and PI–8 derived from 4,4′‐bis(4‐amino‐2‐trifluoromethylphenoxy)biphenyl (2d) and 6FDA were also obtained via a two‐step thermal imidization for comparision with PI–(1–6) on aspects of thermal, mechnical, optical, electrical, and morphological properties. The structure–property relationships of PI–(1–8) were discussed in detail. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.2017,55, 3253–3265
Diagnosis and management of rheumatoid arthritis
Authors: Tracey Gerald
Published: June 2017

Early recognition and treatment of rheumatoid arthritis is the key to a more successful outcome. This article discusses the diagnosis of rheumatoid arthritis and its recommended management.
The human cytomegalovirus nuclear egress complex unites multiple functions: Recruitment of effectors, nuclear envelope rearrangement, and docking to nuclear capsids
Authors: Marschall Manfred , Muller Yves A. , Diewald Benedikt , Sticht Heinrich , Milbradt Jens
Published: June 2017

Background

Nuclear replication represents a common hallmark of herpesviruses achieved by a number of sequentially unrolled regulatory processes. A rate‐limiting step is provided by nucleo‐cytoplasmic capsid export, for which a defined multiregulatory protein complex, namely, the nuclear egress complex (NEC), is assembled comprising both viral and cellular components. The NEC regulates at least 3 aspects of herpesviral nuclear replication: (1) multimeric recruitment of NEC‐associated effector proteins, (2) reorganization of the nuclear lamina and membranes, and (3) the docking to nuclear capsids. Here, we review published data and own experimental work that characterizes the NEC of HCMV and other herpesviruses.

Methods

A systematic review of information on nuclear egress of HCMV compared to selected alpha‐, beta‐, and gamma‐herpesviruses: proteomics‐based approaches, high‐resolution imaging techniques, and functional investigations.

Results

A large number of reports on herpesviral NECs have been published during the last two decades, focusing on protein‐protein interactions, nuclear localization, regulatory phosphorylation, and functional validation. The emerging picture provides an illustrated example of well‐balanced and sophisticated protein networking in virus‐host interaction.

Conclusions

Current evidence refined the view about herpesviral NECs. Datasets published for HCMV, murine CMV, herpes simplex virus, and Epstein‐Barr virus illustrate the marked functional consistency in the way herpesviruses achieve nuclear egress. However, this compares with only limited sequence conservation of core NEC proteins and a structural conservation restricted to individual domains. The translational use of this information might help to define a novel antiviral strategy on the basis of NEC‐directed small molecules.
Immersion‐ and invariance‐based adaptive stabilization of switched nonlinear systems
Authors: Lou Zhi‐E , Zhao Jun
Published: June 2017

This paper presents a novel framework to asymptotically adaptively stabilize a class of switched nonlinear systems with constant linearly parameterized uncertainty. By exploiting the generalized multiple Lyapunov functions method and the recently developed immersion and invariance (I&I) technique, which does not invoke certainty equivalence, we design the error estimator, continuous state feedback controllers for subsystems, and a switching law to ensure boundedness of all closed‐loop signals and global asymptotical regulation of the states, where the solvability of the I&I adaptive stabilization problem for individual subsystems is not required. Then, along with the backstepping method, the proposed design technique is further applied to a class of switched nonlinear systems in strict‐feedback form with an unknown constant parameter so that the I&I adaptive stabilization controllers for the system is developed. Finally, simulation results are also provided to demonstrate the effectiveness of the proposed design method.
Controllability of multiagent systems based on path and cycle graphs
Authors: Liu Xianzhu , Ji Zhijian
Published: June 2017

This paper studies the controllability of multiagent systems based on path and cycle graphs. For paths or cycles, sufficient and necessary conditions are presented for determining the locations of leaders under which the controllability can be realized. Specifically, the controllability of a path is shown to be determined by a set generated only from its odd factors, and the controllability of a cycle is determined by whether the distance between 2 leaders belongs to a set generated from its even (odd) factors when the number of its nodes is even (odd). For both graphs, the dimension of the controllable subspace is also derived. Moreover, the technique used in the derivation of the above results is further used to get sufficient and necessary conditions for several different types of graphs generated from path and cycle topologies. These types of graphs can be regarded as typical topologies in the study of multiagent controllability, and accordingly the obtained results have meaningful enlightenment for the research in this field.
A framework for the meta‐analysis of Bland–Altman studies based on a limits of agreement approach
Authors: Tipton Elizabeth , Shuster Jonathan
Published: June 2017

Bland–Altman method comparison studies are common in the medical sciences and are used to compare a new measure to a gold‐standard (often costlier or more invasive) measure. The distribution of these differences is summarized by two statistics, the ‘bias’ and standard deviation, and these measures are combined to provide estimates of the limits of agreement (LoA). When these LoA are within the bounds of clinically insignificant differences, the new non‐invasive measure is preferred. Very often, multiple Bland–Altman studies have been conducted comparing the same two measures, and random‐effects meta‐analysis provides a means to pool these estimates. We provide a framework for the meta‐analysis of Bland–Altman studies, including methods for estimating the LoA and measures of uncertainty (i.e., confidence intervals). Importantly, these LoA are likely to be wider than those typically reported in Bland–Altman meta‐analyses. Frequently, Bland–Altman studies report results based on repeated measures designs but do not properly adjust for this design in the analysis. Meta‐analyses of Bland–Altman studies frequently exclude these studies for this reason. We provide a meta‐analytic approach that allows inclusion of estimates from these studies. This includes adjustments to the estimate of the standard deviation and a method for pooling the estimates based upon robust variance estimation. An example is included based on a previously published meta‐analysis. Copyright © 2017 John Wiley & Sons, Ltd.
Pilot assessment of vascular endothelial growth factor receptors and trafficking pathways in recurrent and metastatic canine subcutaneous mast cell tumours
Authors: Da Silva Lucas , Fonseca‐Alves Carlos E. , Thompson Jennifer J. , Foster Robert A. , Wood Geoffrey A. , Amorim Renee L. , Coomber Brenda L.
Published: June 2017

Canine subcutaneous mast cell tumour (scMCT) shows less aggressive biological behaviour than cutaneous MCT. Vascular endothelial growth factor receptor 2 (VEGFR2) is expressed by neoplastic cells in canine scMCT, but the relevance of this signalling pathway for disease pathobiology is not clear. The objective of this study was to quantify VEGF‐A, VEGFR2, pVEGFR2, the VEGF co‐receptor Neuropilin 1 (NRP‐1) and the E3 ubiquitin protein ligase c‐Cbl in canine scMCT, and to evaluate their association with disease outcome. Immunohistochemical staining for biomarkers was quantified from 14 cases of canine scMCT using manual and computer‐assisted methods. Kaplan–Meier curves were generated for disease‐free survival (DFS) and compared using Mantel–Cox log‐rank analysis. Cases with high levels of neoplastic cell VEGFR2, pVEGFR2 or c‐CBL immunoreactivity had significantly reduced DFS. All cases displayed neoplastic cells positive for VEGF‐A, which was significantly associated with pVEGFR2 immunoreactivity. There were also significant positive correlations between VEGFR2 and pVEGFR2, and between c‐CBL and pVEGFR2 levels. This pilot study demonstrates the potential utility of these markers in a subset of scMCT in dogs.
Molecular docking studies on thirteen fluoroquinolines with human topoisomerase II a and b
Authors: Jadhav Ashwini Khanderao , Karuppayil Sankunny Mohan
Published: June 2017

DNA relaxation is an important step in DNA replication. DNA topoisomerases play a major role in DNA relaxation. Hence these enzymes are important targets for cancer drugs. DNA topoisomerase inhibitors bind to the transient enzyme–DNA complex and inhibit DNA replication. Various inhibitors of topoisomerase I and II are prescribed as drugs. Topoisomerase II is considered as an important target for the development of anticancer drugs. In this study we have demonstrated molecular docking of thirteen fluoroquinolines with human DNA topoisomerase II alpha (a) and beta (b). Fluoroquinolines are broad spectrum antibacterial antibiotics and it is highly effective against various bacterial infections. Some of the fluoroquinolines like moxifloxacin exert antifungal as well as anti-cancer activity. It forms complexes with topoisomerase II a and are responsible for stoppage DNA replication. Molecular docking studies showed that fluoroquinolines has shown formation of hydrogen bond and good binding affinity with human Topo2a and Topo2b. Hence FQs may inhibit the activity of enzyme topoisomerase by binding at its active site. Ofloxacin, sparafloxacin, ciprofloxacin and moxifloxacin are predicted to be the most potent inhibitors among the thirteen FQs docked. GLN773, ASN770, LYS723 and TRP931 amino acid residues of Topo2a are involved in binding with FQs while ASP479, SER480, ARG820, ARG503, LYS456 and GLN778 amino acid residues of Topo2b are involved in binding with FQs. Our in silico study suggests that fluoroquinolines could be repositioned as DNA topoisomerase II inhibitors hence can be used as anticancer drugs. In vitro and in vivo experiments need to be done to confirm their efficacy.
The Social Defeat Hypothesis of Schizophrenia: an Update
Authors: Van der Ven E.
Published: June 2017

Research provides strong evidence of an elevated risk for developing psychotic symptoms and psychotic disorder among various ethnic and other minority groups. Furthermore, ethnicity may modify the risk for autism-spectrum disorder, but the evidence of this is still thin. Misdiagnosis, selective migration and other methodological artefacts are implausible explanations for the findings on psychotic disorder. Instead, we propose that ‘social defeat’, defined as the chronic experience of being excluded from the majority group, may increase the risk for psychotic disorder by sensitizing the mesolimbic dopamine system. Future challenges lie in connecting the underlying biological mechanisms to behavioral expression in socially excluded groups, as well as in bridging the gap with the clinical field and the wider society by stimulating the implementation of strategies that strengthen the position of minority populations.

Disclosure of interest

The author has not supplied his declaration of competing interest.
Comorbidity of Mental and Physical Disorders: A Major Challenge for Medicine in the 21st Century
Authors: Sartorius N.
Published: June 2017

Demographic changes and successes of medicine in preserving and prolonging life are among the main reasons for the significant increase of comorbidity of mental and physical illness. The simultaneous presence of these disorders leads to a worse prognosis of both types of disorder, significant increases of cost of treatment and heightened mortality.

Although these facts are becoming known among members of the profession and among decision makers in the field of health little is done to provide adequate and timely treatment and care for all the diseases from which a person suffers. The fragmentation of medicine into ever finer and more narrow specialties contributes to the decreasing quality of care for people who have the misfortune of having comorbid mental and physical illnesses as does the stigma of mental illness which decreases the probability of timely help and leads to well documented discrimination of those who have mental illness in health services.

The paper will present some information about comorbidity of mental and physical disorders and suggest reforms of health care that might help to resolve the problems which comorbidity produces.

Disclosure of interest

The author has not supplied his declaration of competing interest.
The Effects of Medication on Default Mode Network (DMN) Connectivity in Attention Deficit/hyperactivity Disorder (ADHD): Bibliographic Review
Authors: Pereira V. , de Castro-Manglano P.
Published: June 2017

Introduction

ADHD is a neurodevelopmental disorder comprising brain structural and functional alterations, especially in default mode network (DMN), as MRI studies have recently shown. However, it is not clear in which extent medication for ADHD may influence the activity of these networks.

Objectives

The main purpose is to look up published evidence about the effects of ADHD medication on the connectivity of DMN in patients as measured with functional-MRI.

Methods

A review was conducted with Pubmed, using search terms ‘default mode network’+ ‘ADHD’ + ‘medication’/‘methylphenidate’/‘atomoxetine’/‘stimulant’/‘lisdexanfetamine’. Original research studies in English using f-MRI to assess DMN connectivity in ADHD patients were included in a more comprehensive review.

Results

The searches found 124 articles, 8 meeting the review criteria. A total size of 146 ADHD patients was comprised (mean size: 18.25 patients). Three studies used specific resting-state f-MRI. Seven were drug trials, 3 of them short-term, randomized and controlled ones. Six included methylphenidate, 2 atomoxetine, 1 lisdexanfetamine and 3 amphetamines. Two also assessed drugs clinical effects. Evidence seems heterogeneous, but mostly consistent with normalizing drug effects on DMN in patients (in some studies also compared with healthy controls), associated with a measured clinical improvement in one study with amphetamines and one with atomoxetine. One trial found little differences on DMN activity.

Conclusions

Psychostimulant drugs and atomoxetine are clinically effective medications; DMN connectivity may partially explain their action mechanisms and constitute a potential response predictor. Further f-MRI studies might more deeply assess the imaging-clinical relationships for each drug.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Ect Combined with Clomipramine and rTMS in an OCD Patient with Secondary Severe Depression
Authors: Mota D. , Almeida F. , Oliveira A. , Silva J. , Gonçalves M. , Ribeiro J. , Martins V. , Andrade J. , Macedo A.
Published: June 2017

Introduction

Obsessive-compulsive disorder (OCD) has high rates of comorbidity with mood disorders, mainly major depressive disorder (MDD). Symptoms of depression are usually secondary to severe and disabling OCD. Electroconvulsive therapy (ECT) has been an effective and well tolerated therapeutic alternative in the management of refractory MDD. Other neuromodulation techniques, such as repetitive transcranial magnetic stimulation (rTMS), have well known efficacy in MDD and also have shown positive results, in clinical trials, treating other psychiatric disorders such as OCD.

Objectives/aims

To determine the efficacy of combining rTMS, ECT and clomipramine in the treatment of severe OCD with comorbid severe MDD.

Methods

The authors report a case of a 54-year-old male patient diagnosed with severe OCD for 23 years. He has been submitted to several drug treatments and intensive cognitive-behavioural therapy (CBT) always with poor response. The patient was admitted in the beginning of 2016 in our inpatient unit. Besides continuing drug treatment (clomipramine IV) and CBT, he was submitted to 12 ECT sessions during one month (3 sessions per week) and to daily sessions of rTMS during the following month.

Outcome measures were obtained using Y-BOCS for OCD and HAM-D for depression.

Results

Our patient responded to ECT with mood improvement after session 4 to full euthymic state at the final session. He also responded well to rTMS with Y-BOCS score reduction.

Conclusion

Combined ECT and rTMS treatment with clomipramine IV and CBT was effective in our patient with a severe form of both disorders (OCD and MDD).

Disclosure of interest

The authors have not supplied their declaration of competing interest.
The Widowhood Effect–mortality and Adverse Health Effects When Losing a Spouse in Old Age
Authors: Kristiansen C.B. , Bojesen A.B. , Munk-Jørgensen P. , Andersen K.
Published: June 2017

Introduction

Losing one's spouse is a major life event which is associated to an increased risk of mental health problems as depression and sleep-disorders. There is also an increased risk of adverse effects on physical health, and even an increased risk of mortality. A phenomena called “the widowhood effect” Though this is well-known clinically, few studies have established the extent of the problem in old age.

Objectives

This study aims to examine the risk of mortality associated to widowhood in old age, and adverse health effects both regarding physical and mental health.

Methods

A nationwide register-based case control study. All Danish people aged 65 years and above who became widowed in the period of 2000–2010 are included. A background population sample of 4:1 is matched on age and gender. By using the personal identification number a linkage between registers containing information regarding health service use, pharmacologic use and demographic information is made. Mortality is analysed using Kaplan-Meier estimate and the statistical comparison between the groups is done by Cox-regression. Adverse health effects are assessed by the health care use and pharmacological use, and are compared between the two groups by t-test, linear and logistic regression depending on the variables.

Results

The study is under conduction, results will be presented.

Conclusions

Widowhood in old age has been associated to an increased risk of mortality and adverse health effects. This study assesses the outcome of this in a nationwide register-based sample.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Validation of a Measure of Positive and Negative Affect for use with Cross-national Older Adults
Authors: Von Humboldt S. , Leal I.
Published: June 2017

Introduction

Positive Affect (PA) and Negative Affect (NA) have been used as general dimensions to describe affective experience, and they are the affective, emotional components of SWB.

Objectives

Positive and negative affect is a relevant facet of well-being for community-dwelling older adults. This study aims to conduct a validation of the Positive and Negative Affect Scale (PANAS), by assessing the psychometric properties (distributional properties, construct, criterion and external-related validities, and reliability) of the PANAS in a cross-national sample of older adults.

Methods

A cross-sectional survey design was used. A convenience sample of 1291 community-dwelling older adults aged 75 years old and older was recruited from community centers. Construct validity was estimated through confirmatory factor analysis and convergent validity. Criterion and external-related validities, reliability and distributional properties were also assessed.

Results

The PANAS demonstrated satisfactory reliability, distributional properties, and construct, criterion and external-related validities in this sample of older adults.

Conclusions

These results suggest that the PANAS can be used as a reliable and valid measure for examining positive and negative affect among cross-national community-dwelling older adults.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
A Checklist for Assessing Dementia-friendly Design: Architecture as Non-pharmacological Mean in Assistance of Patients with Dementia
Authors: Zamfir M.V. , Zamfir Grigorescu M.
Published: June 2017

Introduction

Although there are recommendations regarding dementia-friendly architecture, studies on design features and their impact on quality of life of patients with dementia are quasi-nonexistent. The design of the environment is one of the non-pharmacological methods in the assistance of patients with dementia.

Objectives

Setting a checklist of design principles in order to assess centers for elderly with dementia; identifying the types of centers where will be applied the checklist; implementation of the checklist and determining results of assessment.

Aims

Our aim is to challenge the contemporary architecture of centers for elderly to be friendly with dementia patients.

Methods

After studying literature we built a check-list of 8 principles: providing a comfortable space and also a therapeutically environment; functionality and efficiency; flexibility and accessibility; optimal design of circulation routes in order to avoid disorientation and to reduce agitation; security and safe; aesthetics; sanitation; sustainability. We then performed a case-study on two types of settings, day care centers and respite centers, and we applied the check list on three examples: two urban Day Care Centers for patients with Alzheimer Dementia (2006, Pontevedra, Spain and 2011, Alicante, Spain) and a Respite Center (2009, Dublin, Ireland).

Results

In general, the centers are verifying the proposed checklist. Four architectural tools were identified: light, form, colour and texture. Form is more recognizable than colour and colour more recognizable than function.

Conclusions

Architecture contributes to increase quality of life in people with dementia. The proposed checklist is a promising tool for assessing dementia-friendly design.

Disclosure of interest

The authors have not supplied their declaration of competing interest.