bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanism of product inhibition for cellobiohydrolase Cel7A during hydrolysis of insoluble cellulose
Authors: Olsen Johan P. , Alasepp Kadri , Kari Jeppe , Cruys‐Bagger Nicolaj , Borch Kim , Westh Peter
Published: December 2015

The cellobiohydrolase cellulase Cel7A is extensively utilized in industrial treatment of lignocellulosic biomass under conditions of high product concentrations, and better understanding of inhibition mechanisms appears central in attempts to improve the efficiency of this process. We have implemented an electrochemical biosensor assay for product inhibition studies of cellulases acting on their natural substrate, cellulose. Using this method we measured the hydrolytic rate of Cel7A as a function of both product (inhibitor) concentration and substrate load. This data enabled analyses along the lines of conventional enzyme kinetic theory. We found that the product cellobiose lowered the maximal rate without affecting the Michaelis constant, and this kinetic pattern could be rationalized by two fundamentally distinct molecular mechanisms. One was simple reversibility, that is, an increasing rate of the reverse reaction, lowering the net hydrolytic velocity as product concentrations increase. Strictly this is not a case of inhibition, as no catalytically inactive is formed. The other mechanism that matched the kinetic data was noncompetitive inhibition with an inhibition constant of 490 ± 40 μM. Noncompetitive inhibition implies that the inhibitor binds with comparable strength to either free enzyme or an enzymesubstrate complex, that is, that association between enzyme and substrate has no effect on the binding of the inhibitor. This mechanism is rarely observed, but we argue, that the special architecture of Cel7A with numerous subsites for binding of both substrate and product could give rise to a true noncompetitive inhibition mechanism. Biotechnol. Bioeng. 2016;113: 1178–1186. © 2015 Wiley Periodicals, Inc.
Improved Efficiency for Partial Oxidation of Methane by Controlled Copper Deposition on Surface‐Modified ZSM‐5
Authors: Sheppard Thomas , Daly Helen , Goguet Alex , Thompson Jillian M.
Published: December 2015

The mono(μ‐oxo) dicopper cores present in the pores of Cu‐ZSM‐5 are active for the partial oxidation of methane to methanol. However, copper on the external surface reduces the ratio of active, selective sites to unselective sites. More efficient catalysts are obtained by controlling the copper deposition during synthesis. Herein, the external exchange sites of ZSM‐5 samples were passivated by bis(trimethylsilyl) trifluoroacetamide (BSTFA) followed by calcination, promoting selective deposition of intraporous copper during aqueous copper ion exchange. At an optimum level of 1–2 wt % SiO2, IR studies showed a 64 % relative reduction in external copper species and temperature‐programmed oxidation analysis showed an associated increase in the formation of methanol compared with unmodified Cu‐ZSM‐5 samples. It is, therefore, reported that the modified zeolites contained a significantly higher proportion of active, selective copper species than their unmodified counterparts with activity for partial methane oxidation to methanol.
Mechanism and Charge Effect of Cycloisomerization of ω‐Alkynylfuran Catalyzed by Subnanometer Gold Clusters: A Theoretical Study
Authors: Tang Dianyong , Yang Miao , Zhang Jin , He Rongxing , Shen Wei , Li Ming
Published: December 2015

The detailed reaction mechanism of the ω‐alkynylfuran cycloisomerization catalyzed by medium‐sized bare Au38 nanoclusters was investigated by means of density functional theory at the Perdew–Burke–Ernzerhof level of theory. Both the charge and size effects of the three‐dimensional gold clusters are studied at the same level. The mechanistic studies show that the 5‐exo Friedel–Crafts‐type mechanism is the most favorable mechanism, and could be selective to form phenol derivatives. Additionally, the solvation effect of acetonitrile apparently lowers the energy barrier of the first and second steps of the reaction. The positive charge on the gold clusters could enhance the catalytic activity of the clusters. Suitable positive charges on the reaction sites are essential for the formation of phenol through the cycloisomerization of ω‐alkynylfuran. The subnanometer gold clusters show high catalytic efficiency for the conversion of ω‐alkynylfurans to phenol derivatives.
NaOH‐Aided Platinum Nanoparticle Size Regulation on Polybenzimidazole‐Wrapped Carbon Nanotubes for Use as Non‐Humidified Polymer Electrolyte Fuel Cell Catalyst
Authors: Yang Zehui , Fujigaya Tsuyohiko , Nakashima Naotoshi
Published: December 2015

We describe a method to control the size of platinum nanoparticles (Pt‐NPs) on poly[2,2′‐(2,6‐pyridine)‐5,5′‐bibenzimidazole] (PyPBI)‐wrapped pristine multi‐walled carbon nanotubes (MWNTs) without changing the loading amount by adding various concentrations of sodium hydroxide (NaOH) to the ethylene glycol aqueous solutions. The Pt‐NP sizes decreased from 3.8±0.4 to 1.7±0.1 nm with increasing NaOH concentrations. The mass activity of the oxygen reduction reaction was 224 mA mgPt−1 for the electrocatalyst with 3 nm Pt‐NPs, in which the power density reached 350 mW cm−2, which was 1.4 times higher than that of the electrocatalyst synthesized without NaOH (250 mW cm−2) at 120 °C and without any extra humidification. The electrocatalyst synthesized from a small amount of additional NaOH (0.5 mm) in the starting solution shows an enhanced performance and similar Pt stability. More importantly, the Pt‐NP size showed no effect on the Pt stability owing to the use of the PyPBI.
Toward the Control of the Creation of Mixed Monolayers on Glassy Carbon Surfaces by Amine Oxidation
Authors: Groppi Jessica , Bartlett Philip N. , Kilburn Jeremy D.
Published: December 2015

A versatile and simple methodology for the creation of mixed monolayers on glassy carbon (GC) surfaces was developed, using an osmium–bipyridyl complex and anthraquinone as model redox probes. The work consisted in the electrochemical grafting on GC of a mixture of mono‐protected diamine linkers in varying ratios which, after attachment to the surface, allowed orthogonal deprotection. After optimisation of the deprotection conditions, it was possible to remove one of the protecting groups selectively, couple a suitable osmium complex and cap the residual free amines. The removal of the second protecting group allowed the coupling of anthraquinone. The characterisation of the resulting surfaces by cyclic voltammetry showed the variation of the surface coverage of the two redox centres in relation to the initial ratio of the linking amine in solution.
Access to Versatile β‐Cyclodextrin Scaffolds through Guest‐Mediated Monoacylation
Authors: Vurgun Nesrin , Gómez‐Biagi Rodolfo F. , Nitz Mark
Published: December 2015

Herein, we report the selective mono‐derivatization of heptakis[6‐deoxy‐6‐(2‐aminoethylsulfanyl)]‐β‐CD (1) through a guest‐mediated covalent capture strategy. The use of guests functionalized with cleavable linkers enables the installation of an amine‐orthogonal thiol group on the primary rim of 1 as a handle for further transformations to the β‐CD scaffold. Applying this methodology, two novel monoderivatized β‐CDs were obtained in good yield and high purity. Both of these monoacylated CDs were amenable to facile linker cleavage and further modification at the resulting thiol group. This methodology can be applied towards the synthesis heterofunctionalized β‐CD constructs for analyte sensing, drug delivery, and other applications.
Magnetocaloric Properties of Heterometallic 3d–Gd Complexes Based on the [Gd(oda)3]3− Metalloligand
Authors: Qiu Jiang‐Zhen , Wang Long‐Fei , Chen Yan‐Cong , Zhang Ze‐Min , Li Quan‐Wen , Tong Ming‐Liang
Published: December 2015

A series of heterometallic 3d–Gd3+ complexes based on a lanthanide metalloligand, [M(H2O)6][Gd(oda)3]⋅3 H2O [M=Cr3+ (1‐Cr)] (H2oda=2,2′‐oxydiacetic acid), [M(H2O)6][MGd(oda)3]2⋅3 H2O [M=Mn2+ (2‐Mn), Fe2+ (2‐Fe) and Co2+ (2‐Co)], and [M3Gd2(oda)6(H2O)6]⋅12 H2O [M=Ni2+ (3‐Ni), Cu2+ (3‐Cu), and Zn2+ (3‐Zn)], are reported. Magnetic and heat‐capacity studies revealed a significant impact on the magnetocaloric effect depending on the anisotropy of the 3d transition metal ions, as confirmed by comparison of the observed maximum values of −ΔSm between complexes 2‐Co and 1‐Cr. In these two complexes, the 3d metal ions have the same spin (S=3/2 for Co2+ and Cr3+ ions), and the theoretical calculation suggested a larger −ΔSm value for 2‐Co (47.8 J K−1 kg−1) than 1‐Cr (37.5 J K−1 kg−1); however, the significant anisotropy of Co2+ ions in 2‐Co, which can result in smaller effective spins, gives a smaller value of −ΔSm for 2‐Co (32.2 J K−1 kg−1) than for 1‐Cr (35.4 J K−1 kg−1) at ΔH=9 T.
[4+3] Cycloaddition of Donor–Acceptor Cyclopropanes with Amphiphilic Benzodithioloimine as Surrogate for ortho‐Bisthioquinone
Authors: Garve Lennart K. B. , Pawliczek Martin , Wallbaum Jan , Jones Peter G. , Werz Daniel B.
Published: December 2015

Donor–acceptor cyclopropanes were reacted with amphiphilic benzodithioloimine to give seven‐membered heterocycles with two sulfur atoms. Formally, this transformation can be regarded as a [4+3] cycloaddition reaction of the three‐membered ring and ortho‐bisthioquinone. The benzodithioloimine serves as a surrogate for this highly reactive diene. The structure of the products was confirmed by X‐ray crystallography. Broad signals in 13C NMR studies suggest that several conformers, slowly interconverting on the NMR timescale, are present at room temperature.
Absolute Configuration Assignment of a Paraconic Acid Derivative via Vibrational Circular Dichroism Spectroscopy and Density Functional Theory Calculation
Authors: Meninno Sara , Rizzo Paola , Abbate Sergio , Longhi Giovanna , Mazzeo Giuseppe , Monaco Guglielmo , Lattanzi Alessandra , Zanasi Riccardo
Published: December 2015

Density functional theory calculation of the vibrational circular dichroism spectrum was used to assign the absolute configuration of an all‐carbon quaternary β‐stereocenter of a γ‐butyrolactone recently synthesized through an asymmetric organocatalytic tandem aldol/lactonization sequence. Comparison with the experimental spectrum is satisfactory, on account of the fact that spectroscopic features are weak due to the presence of multiple conformers. As a result, the (R) absolute configuration was assigned to the (+) optical isomer. Chirality 28:110–115, 2016. © 2015 Wiley Periodicals, Inc.
Towards the Limits of Vibrational Circular Dichroism Spectroscopy: VCD Spectra of Some Alkyl Vinylethers
Authors: Zinna Francesco , Pescitelli Gennaro
Published: December 2015

Three alkyl vinylethers from our collection of chiral samples were investigated through VCD spectroscopy, in combination with Density Functional Theory (DFT) calculations. Despite the simplicity of the compounds, reproducing all the spectral features is an involved task, since the many significantly populated conformers contribute to the total VCD spectrum with bands which often have opposite signatures. Nevertheless, we show that certain bands can be satisfactorily reproduced by calculation and therefore they may be employed for the determination of absolute configuration in these and similar compounds, for which no simple alternative method is available. Chirality 28:143–146, 2016. © 2015 Wiley Periodicals, Inc.
Separation of Enantiomers by Inclusion Gas Chromatography: On the Influence of Water in the Molecular Complexation of Methyl 2‐Chloropropanoate Enantiomers and the Modified γ‐Cyclodextrin Lipodex‐E
Authors: Mandoli Alessandro , Schurig Volker
Published: December 2015

A profound influence of water has previously been detected in the complexation of the enantiomers of methyl 2‐chloropropanoate (MCP) and the chiral selector octakis(3‐O‐butanoyl‐2,6‐di‐O‐pentyl)‐γ‐cyclodextrin (Lipodex‐E) in NMR and sensor experiments. We therefore investigated the retention behavior of MCP enantiomers on Lipodex‐E by gas chromatography (GC) under hydrous conditions. Addition of water to the N2 carrier gas modestly reduced the retention factors k of the enantiomers, notably for the second eluted enantiomer (S)‐MCP. This resulted in an overall decrease of enantioselectivity ‐ΔS,R(ΔG) in the presence of water. The effect was fully reversible. Consequently, for a conditioned column in the absence of residual water, the determined thermodynamic data, i.e. ΔS,R(ΔH) = –12.64 ± 0.08 kJ mol‐1 and ΔS,R(ΔS) = –28.18 ± 0.23 J K‐1 mol‐1, refer to a true 1:1 complexation process devoid of hydrophobic hydration. Chirality 28:124–131, 2015. © 2015 Wiley Periodicals, Inc.
Increasing the Energy Efficiency of Batch‐Type Drying with Partial Air Recirculation
Authors: Ziegler Thomas , Jubaer Hasan , Schütz Marco
Published: December 2015

Partial recirculation of the dryer outlet air is a common practice in many batch‐type drying processes. However, energy consumption and total duration of drying are directly affected by the recycled air ratio (RAR). In order to assess the influence of different ambient air conditions on favorable values of RAR, a new quantity is introduced. The so‐called critical drying efficiency determines the most favorable starting point for partial air recirculation. It is shown that by increasing RAR successively in the further course of drying, substantial energy savings can be achieved with only a marginal extension of drying duration. It is also pointed out that optimized control of drying plants should be based not only on dryer outlet air conditions but also on ambient air conditions.
Fighting Cancer with Transition Metal Complexes: From Naked DNA to Protein and Chromatin Targeting Strategies
Authors: Palermo Giulia , Magistrato Alessandra , Riedel Tina , von Erlach Thibaud , Davey Curt A. , Dyson Paul J. , Rothlisberger Ursula
Published: December 2015

Many transition metal complexes have unique physicochemical properties that can be efficiently exploited in medicinal chemistry for cancer treatment. Traditionally, double‐stranded DNA has been assumed to be the main binding target; however, recent studies have shown that nucleosomal DNA as well as proteins can act as dominant molecular binding partners. This has raised new questions about the molecular determinants that govern DNA versus protein binding selectivity, and has offered new ways to rationalize their biological activity and possible side effects. To address these questions, molecular simulations at an atomistic level of detail have been used to complement, support, and rationalize experimental data. Herein we review some relevant studies—focused on platinum and ruthenium compounds—to illustrate the power of state‐of‐the‐art molecular simulation techniques and to demonstrate how the interplay between molecular simulations and experiments can make important contributions to elucidating the target preferences of some promising transition metal anticancer agents. This contribution aims at providing relevant information that may help in the rational design of novel drug‐discovery strategies.
The Three Possible 2‐(Pyrenylethynyl) Adenosines: Rotameric Energy Barriers Govern the Photodynamics of These Structural Isomers
Authors: Reuss Andreas J. , Grünewald Christian , Braun Markus , Engels Joachim W. , Wachtveitl Josef
Published: December 2015

This article presents a comprehensive study of the photophysics of 2‐(2‐pyrenylethynyl) adenosine and 2‐(4‐pyrenylethynyl) adenosine, which are structural isomers of the well‐established fluorescent RNA label 2‐(1‐pyrenylethynyl) adenosine. We performed steady‐state and ultrafast transient absorption spectroscopy studies along with time‐resolved fluorescence emission experiments in different solvents to work out the interplay of locally excited and charge‐transfer states. We found the ultrafast photodynamics to be crucial for the fluorescence decay behavior, which extends up to tens of nanoseconds and is partially multi‐exponential. These features in the ultrafast dynamics are indicative of the rotational energy barriers in the first excited state.
Reply to Pardo et al. 2015 on ‘Reply to comment on Couto‐Mendoza et al. 2014. More complexity does not always mean more accuracy: the case of IBMWP and METI in NW Spain’ Ecohydrology DOI: 10.1002/eco.1660
Authors: Couto‐Mendoza M.T. , Vieira‐Lanero R. , Cobo F.
Published: December 2015

The manuscript “More complexity does not always mean more accuracy: the case of IBMWP and METI in NW Spain” compares the behaviour of one multimetric index (METI), proposed for NW Spain rivers, and the IBMWP, excluded from the Spanish Water Planning Instruction for NW Spain rivers, under the same conditions in the Miño‐Sil Basin District (DHMS) in the NW Spain. The conclusion of that assay is that both indices are useful tools for evaluating the ecological status of the running‐water ecosystems in the NW Spain, and emphasises the use of the IBMWP, because it may be better (more practical) than the METI, which has already been proposed for the same goal in this region. Another topic to deal with in the report was the number of established reference sites in the DHMS. Pardo et al. () give 5 replies to 5 criticisms that question the use of the METI in the NW Spain. Pardo et al. (2015) mention that those criticisms are contained in Couto‐Mendoza et al. (). Overall, Pardo et al. () highlight the validity of the METI as a method for assessing the ecological status because, unlike the IBMWP that they reject, it has been intercalibrated in the European exercise in the Central Baltic Rivers GIG. Each reply to the criticisms selected by Pardo et al. () is discussed. Copyright © 2015 John Wiley & Sons, Ltd.
Non‐steroidal mineralocorticoid receptor antagonism for the treatment of cardiovascular and renal disease
Authors: Bramlage Peter , Swift Stephanie L. , Thoenes Martin , Minguet Joan , Ferrero Carmen , Schmieder Roland E.
Published: December 2015

Pharmaceutical antagonism of the mineralocorticoid receptor (MR) can protect against organ damage caused by elevated aldosterone levels in patients experiencing heart failure (HF), chronic kidney disease (CKD), primary aldosteronism, and hypertension. While traditional steroid‐based MR antagonists effectively reduce mortality rates and extend patient survival, their broad application has been limited by significant side effects, most notably hyperkalaemia. Recently, finerenone (BAY 94‐8862) has emerged as a next‐generation non‐steroidal dihydropyridine‐based MR antagonist designed to minimize off‐target effects while maintaining potent efficacy. In this review, the outcomes of finerenone therapy in several diseases associated with MR activity are explored. The (pre‐) clinical efficacy of finerenone is compared with that of traditional steroid‐based MR antagonists. Finally, recent and ongoing clinical trials using finerenone to treat chronic HF, CKD, and diabetic nephropathy are discussed. Taken together, pre‐clinical and clinical evidence suggests that finerenone may achieve equivalent organ‐protective effects with reduced levels of electrolyte disturbance compared with traditional steroid‐based MR antagonists. This supports further clinical development of finerenone for the treatment of cardiovascular and renal disease.
Early right ventricular response to cardiac resynchronization therapy: impact on clinical outcomes
Authors: Stolfo Davide , Tonet Elisabetta , Merlo Marco , Barbati Giulia , Gigli Marta , Pinamonti Bruno , Ramani Federica , Zecchin Massimo , Sinagra Gianfranco
Published: December 2015

Aims

Right ventricular (RV) dysfunction has been associated with a worse outcome in heart failure patients undergoing CRT. However, evidence on the RV response to CRT is controversial and there are no data regarding the early effects of CRT on RV function (RVF). We sought to investigate whether a CRT device favourably influences the RVF acutely after implantation, impacting on long‐term outcomes.

Methods and results

Patients who successfully underwent CRT device implantation from January 2005 to January 2014 were retrospectively analysed. RV dysfunction was defined by an RV fractional area change <35%. Post‐procedural echocardiographic evaluation was performed at a median time of 2 days (interquartile range 1–6 days). The primary endpoint was a composite of all‐cause mortality and urgent heart transplantation. A total of 194 patients with available pre‐ and post‐procedural RVF assessment were included. Sixty‐two (32%) presented an impaired RVF before the procedure. Of them, 32% showed prompt normalization of RVF following CRT. This occurred in parallel with a large improvement in pulmonary arterial pressure, mitral regurgitation, E/E′ ratio, and diastolic function. Pre‐implantation independent predictors of early RVF normalization were LBBB (P = 0.034) and higher systolic blood pressure (P = 0.026). Improvement in RVF was independently associated with a better long‐term prognosis at multivariable analysis [hazard ratio 0.124; 95% confidence interval 0.016–0.966, P = 0.04).

Conclusions

Acute normalization of RVF can be observed after CRT along with haemodynamic improvement, and therefore can be used as an independent predictor of transplant‐free survival.
Concentrations of polycyclic aromatic hydrocarbons in New York City community garden soils: Potential sources and influential factors
Authors: Marquez-Bravo Lydia G. , Briggs Dean , Shayler Hannah , McBride Murray , Lopp Donna , Stone Edie , Ferenz Gretchen , Bogdan Kenneth G. , Mitchell Rebecca G. , Spliethoff Henry M.
Published: December 2015

A total of 69 soil samples from 20 community gardens in New York City (New York, USA) were collected and analyzed for 23 polycyclic aromatic hydrocarbons (PAHs) and black carbon. For each garden, samples were collected from nongrowing areas (non-bed) and from vegetable-growing beds, including beds with and without visible sources of PAHs. The sum of the US Environmental Protection Agency's 16 priority PAHs ranged up to 150 mg/kg, and the median (5.4 mg/kg) and mean (14.2 mg/kg) were similar to those previously reported for urban areas in the northeast United States. Isomer ratios indicated that the main sources of PAHs were petroleum, coal, and wood combustion. The PAH concentrations were significantly and positively associated with black carbon and with modeled air PAH concentrations, suggesting a consistent relationship between historical deposition of atmospheric carbon-adsorbed PAHs and current PAH soil concentrations. Median PAH soil concentration from non-bed areas was higher (7.4 mg/kg) than median concentration from beds in the same garden (4.0 mg/kg), and significantly higher than the median from beds without visible sources of PAHs (3.5 mg/kg). Median PAH concentration in beds from gardens with records of soil amendments was 58% lower compared with beds from gardens without those records. These results suggest that gardening practices in garden beds without visible sources of PAHs contribute to reduce PAH soil concentrations. Environ Toxicol Chem 2016;35:357–367. © 2015 SETAC
Net methylmercury production in 2 contrasting stream sediments and associated accumulation and toxicity to periphyton
Authors: Klaus Jaclyn E. , Hammerschmidt Chad R. , Costello David M. , Burton G. Allen
Published: December 2015

Periphyton uptake of bioaccumulative methylmercury (MeHg) may be an important entryway into the food web of many stream ecosystems where periphyton can be dominant primary producers. The net production of MeHg in stream sediment, its bioaccumulation in periphyton, and the potential toxicity of divalent Hg (Hg[II]) and MeHg in sediment to periphyton were investigated with a 67-d in situ incubation experiment using chemical exposure substrates containing either a fine-grained, organic-rich or a sandy, low-organic sediment, each amended with varying concentrations of mercuric chloride. Methylmercury was produced in sediment, and concentrations increased with greater amounts of added Hg(II); however, the net production of MeHg was inhibited in the highest Hg(II) treatments of both sediments. The range of total Hg concentrations that inhibited MeHg production was between approximately 80 000 ng Hg and 350 000 ng Hg per gram of organic matter for both sediments. Periphyton colonizing substrates accumulated MeHg in proportion to the concentration in sediment, but periphyton exposed to the sandy sediment accumulated approximately 20-fold more than those exposed to the organic-rich sediment relative to sediment MeHg concentrations. Toxicity of either Hg(II) or MeHg to periphyton was not observed with either periphyton organic content, net primary production, or respiration as endpoints. These results suggest that in situ production and bioaccumulation of MeHg in stream ecosystems can vary as a function of sediment characteristics and Hg(II) loadings to the sediment. Environ Toxicol Chem 2016;35:1759–1765. © 2015 SETAC
An Integrative Psychotherapy Approach to Foster Community Engagement and Rehabilitation in Schizophrenia: A Case Study Illustration
Authors: Kukla Marina , Whitesel Frankie , Lysaker Paul H.
Published: December 2015

This case study illustrates the use of a long‐term integrative psychotherapy approach with a middle‐ aged man with chronic schizophrenia and a mood disorder. The case of “Holst” describes a man with a history of insecure attachment and trauma who later went on to contract a serious chronic illness, precipitating the onset of psychotic symptoms, depression, and chronic suicidal ideation, resulting in multiple hospitalizations. Combining metacognition‐oriented therapy with elements of cognitive behavioral therapy and psychiatric rehabilitation, this approach fostered significantly improved community functioning and attainment of personal goals over time. Through the journey of therapy, the patient also developed a more coherent narrative about his life, established a stable sense of self, and became an active agent in the world. This case illustration demonstrates that these three different approaches can be used in a sequential and complementary fashion to foster recovery in the midst of serious physical and mental illness.
Pharmacokinetics, Pharmacodynamics, Safety, and Clinical Activity of Multiple Doses of RCT‐18 in Chinese Patients With Systemic Lupus Erythematosus
Authors: Zhao Qian , Chen Xia , Hou Yong , Jiang Ji , Zhong Wen , Yao Xuejing , Wang Wenxiang , Li Lin , Fang Jianmin , Zhang Fengchun , Hu Pei
Published: December 2015

RCT‐18 is a novel recombinant fusion protein that blocks the activity of a B‐lymphocyte stimulator and a proliferation‐inducing ligand. This was a randomized, single‐blind, and placebo‐controlled phase 1 study in 12 patients with systemic lupus erythematosus. Eligible patients were randomized 3:1 to receive multiple subcutaneous doses of RCT‐18 for 4 weeks (180 mg, once weekly) or placebo and monitored over an 84‐day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety, and clinical activity. After multiple‐dose RCT‐18, the maximal serum concentration (Cmax) of total and free RCT‐18 was reached within 1 to 2 days. Mean elimination half‐life for total RCT‐18 and free RCT‐18 was 11.4 to 26.4 days and 2.4 to 26.5 days, respectively. Slight accumulation was found after multiple subcutaneous administrations. The average accumulation ratios of AUC and Cmax after the fourth administration of RCT‐18 were 2.0 and 1.7 for total RCT‐18, and 1.8 and 1.6 for free RCT‐18. The formation and elimination of BLyS‐RCT‐18 complex were much slower, with a time to Cmax of 14 to 46 days. Pharmacokinetic characteristics of RCT‐18 in SLE patients were similar to those in patients with rheumatoid arthritis. No positive reaction was detected in the immunogenicity assessments. RCT‐18 was biologically active, according to serum immunoglobulin and B‐cell levels. Treatment‐related IgM and IgA reduction was found during this study. CD19+, IgD+, and CD27+ B‐cell counts were increased after administration and decreased subsequently. SLE patients treated with RCT‐18 were more prone to infections, including moderate and severe infections. Lower dosages of RCT‐18 should be considered in further clinical development.
Patient‐centred physical therapy is (cost‐) effective in increasing physical activity and reducing frailty in older adults with mobility problems: a randomized controlled trial with 6 months follow‐up
Authors: de Vries Nienke M. , Staal J Bart , van der Wees Philip J. , Adang Eddy M. M. , Akkermans Reinier , Olde Rikkert Marcel G. M. , Nijhuis‐van der Sanden Maria W. G.
Published: December 2015

Background

Despite the well‐known health benefits of physical activity, it is a great challenge to stay physically active for frail–older adults with mobility limitations. The aim of this study was to test the (cost‐) effectiveness of a patient‐centred physical therapy strategy (Coach2Move) in which individualized treatment (motivational interviewing, physical examination, individualized goal setting, coaching and advice on self management, and physical training) is combined to increase physical activity level and physical fitness and, thereby, to decrease the level of frailty.

Methods

A randomized controlled trial was performed in 13 physical therapy practices with measurements at 3 and 6 months. Eligible patients were aged 70 years or over and had mobility problems (i.e. difficulties with walking, moving, getting up and changing position from bed or chair to standing, or stair climbing). The primary outcome was physical activity (total and moderate intensity) in minutes per day. Secondary outcomes were as follows: frailty, walking speed and distance, mobility, and quality of life. Data were analysed using linear mixed models for repeated measurements. Healthcare costs and quality‐adjusted life years (QALYs) were computed and combined using net monetary benefit (NMB) for different willingness to pay thresholds. Data on costs, QALYs, and NMBs were analysed using linear mixed models.

Results

One hundred and thirty patients participated in this study. At 6 months, the between‐group difference was significant for moderate‐intensity physical activity in favour of the Coach2Move group [mean difference: 17.9 min per day; 95% confidence interval (CI) 4.0 to 34.9; P = 0.012]. The between‐group difference for total physical activity was 14.1 min per day (95% CI −6.6 to 34.9; P = 0.182). Frailty decreased more in the Coach2Move group compared with usual care [mean difference: −0.03 (95% CI: −0.06 to −0.00; P = 0.027)]. Compared with usual treatment, the Coach2Move strategy resulted in cost savings (€849.8; 95% CI: 1607 to 90; P = 0.028), an improvement in QALYs, (0.02; 95% CI: 0.00 to 0.03; P = 0.03), and a higher NMB at every willingness to pay threshold.

Conclusions

Older adults with mobility problems are able to safely increase physical activity in their own environment and reduce frailty. This study emphasizes both the potential cost‐effectiveness of a patient‐centred approach in the frail elderly and the importance of physical activity promotion in older adults with mobility limitations.
Telechelic Poly(methyl acrylate)s as Constituents for Multiblock Poly(urethane urea)s
Authors: Couthouis Justine , Keul Helmut , Möller Martin
Published: December 2015

New poly(urethane urea)s based on telechelic poly(methyl acrylate)s (PMAs) and different diisocyanates and diamines are prepared by a two‐step polyaddition process—formation of an isocyanate telechelic prepolymer followed by chain extension with a diamine to form the final poly(urethane urea)s. Hydroxyl‐telechelic or mixed amino‐hydroxyl‐telechelic PMAs are obtained by two different concepts: (i) according to the first concept methyl acrylate (MA) was polymerized by single electron transfer‐living radical polymerization (SET‐LRP) using 2‐hydroxyethyl 2‐bromoisobutyrate as initiator followed by nucleophilic substitution of the halogen end group with n‐butylamine, 2‐methylamino ethanol, or 3‐amino‐1‐propanol and (ii) according to the second concept after SET‐LRP under the same conditions the halogen end group is converted to an azide followed by a click reaction using sodium azide and propargyl alcohol in a one‐pot reaction. Applying the second concept, a hydroxyl‐functional PMA with a share of 83 mol% bifunctionality is obtained. This PMA‐diol is used in polyaddition reaction with different diisocyanates (isophorone diisocyanate (IPDI), 4,4′‐methylenebis(cyclohexyl isocyanate) (HMDI), and 4,4′‐methylenediphenyl diisocyanate (MDI)) resulting in an isocyanate‐telechelic prepolymer followed by chain extension with the corresponding diamines (isophorone diamine (IPDA), 4,4′‐methylenebis(cyclohexyl amine) (HMDA), and 4,4′‐methylenediphenyl diamine (MDA)). The polyurethane based on hydroxyl‐telechelic PMAs and IPDI/IPDA has a molecular weight of Mn = 44 500 g mol−1 and a dispersity Đ = 3.5, respectively; those based on HMDI/HMDA and MDI/MDA have Mn = 24 600 g mol−1 and Đ = 2.2 and Mn = 16 100 g mol−1 and Đ = 2.0, respectively.

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End Group Functionalization of PFpP Macromolecules Via Fp Migration Insertion Reactions
Authors: Cao Kai , Wang Xiaosong
Published: December 2015

PFpP macromolecules, synthesized via migration insertion polymerization of CpFe(CO)2(CH2)3PPh2 (FpP), exhibit reactive Fp end groups for further migration insertion reactions in the presence of phosphines. A number of alkyl diphenylphosphines with varied alkyl length, Ph2PCn (n = 6, 10, 18), have been prepared for the reaction, resulting in PFpP‐PPh2Cn (n = 6, 10, 18) amphiphiles. The phosphines with longer alkyl chains impose steric hindrance for the reaction and therefore require longer reaction times and excess phosphines relative to PFpP.

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Neuroimaging correlates of blinking abnormalities in patients with progressive supranuclear palsy
Authors: Bologna Matteo , Piattella Maria Cristina , Upadhyay Neeraj , Formica Alessandra , Conte Antonella , Colosimo Carlo , Pantano Patrizia , Berardelli Alfredo
Published: December 2015

Objective

We aimed to identify the possible relationship between blinking abnormalities and neuroimaging changes in patients with progressive supranuclear palsy.

Methods

We studied 18 patients with progressive supranuclear palsy and 13 healthy subjects. Voluntary and spontaneous blinking were recorded using kinematic techniques. Changes in brain structures were detected by T1‐weighted magnetic resonance imaging and voxel‐based morphometry. We then sought possible correlations between blinking and neuroimaging abnormalities in patients.

Results

Kinematic analysis indicated several abnormalities during voluntary blinking and a markedly reduced spontaneous blink rate in patients compared with healthy subjects. Neuroimaging showed gray matter loss in cortical and subcortical structures and lower white matter volume in the brainstem. Gray matter loss in subcortical structures correlated with the prolonged pause duration between the closing and opening phases, during voluntary blinking.

Conclusions

This study provides a more specific insight into the pathophysiological mechanisms underlying blinking abnormalities in progressive supranuclear palsy. © 2015 Movement Disorder Society
A high order finite volume method for one dimensional nonlocal reactive flows of parabolic type
Authors: Wang Lejuan , Yang Min
Published: December 2015

In this paper, we consider a high order finite volume approximation of one‐dimensional nonlocal reactive flows of parabolic type. The method is obtained by discretizing in space by arbitrary order vertex‐centered finite volumes, followed by a modified Simpson quadrature scheme for the time stepping. Compared to the existed finite volume methods, this new finite volume scheme could achieve the desired accuracy with less data storage by employing higher‐order trial spaces. The finite volume approximations are proved to possess optimal order convergence rates in the H1‐norm and L2‐norm, which are also confirmed by numerical tests. Copyright © 2015 John Wiley & Sons, Ltd.
A monotone nonlinear finite volume method for approximating diffusion operators on general meshes
Authors: Camier Jean‐Sylvain , Hermeline Francois
Published: December 2015

The basic principles of the discrete duality and nonlinear monotone finite volume methods are combined in order to obtain a new monotone nonlinear finite volume method for the approximation of diffusion operators on general meshes. Numerical results highlight both the second‐order accuracy of this method on general meshes and its capability to deal with challenging anisotropic diffusion problems on various computational domains. Copyright © 2016 John Wiley & Sons, Ltd.
Defect reduced selectively grown GaN pyramids as template for green InGaN quantum wells
Authors: Wagner J. , Wächter C. , Wild J. , Müller M. , Metzner S. , Veit P. , Schmidt G. , Jetter M. , Bertram F. , Zweck J. , Christen J. , Michler P.
Published: December 2015

Abstractauthoren We report the growth of green emitting InGaN quantum wells (QWs) by metal‐organic vapor‐phase epitaxy (MOVPE) on three‐dimensional GaN templates. The facets of GaN pyramids, fabricated by selective‐area growth (SAG), reduce the influence of the quantum‐confined Stark effect (QCSE) on the emission properties of the QW. The luminescence properties of a QW are a good indicator for the crystalline quality of the GaN layer beneath. Especially the presence of voids inside the pyramids, as well as stacking faults (SFs) and threading dislocations (TDs) in the wing region strongly influence the strain situation and the incorporation of In into the overlying InGaN layer. Thus, the crystal quality of the GaN pyramid has a strong influence on the efficiency and the emission properties of the active region. Therefore, a low‐temperature nucleation on the GaN buffer in conjunction with a decreasing Ga‐flux taking the decreasing c‐plane growth surface of the pyramid into account was introduced. The low‐temperature photoluminescence (PL) properties of the InGaN QW reveal the differences between the standard formation of the pyramid and this modified growth. Cathodoluminescence (CL) and transmission electron microscopy (TEM) measurements confirm the differences between the two growth modes in the crystal quality of the inner part of the pyramid.
Effect of NaCl concentration on corrosion of Al alloy during repeated wet–dry cycle tests at 323 K—comparing with corrosion in immersion tests‐
Authors: Chiba Makoto , Saito Shu , Nagai Kanae , Takahashi Hideaki , Shibata Yutaka
Published: December 2015

Corrosion of 4043‐Al alloy was examined by repeated wet–dry cycle tests with NaCl solutions at 323 K, and compared with immersion test corrosion in 0.2–5.5 kmol/m3 NaCl solutions. The Al alloy specimens after the immersion tests for 86.4 ks (1 day) or 604.8 ks (7 days) showed preferential dissolution of the aluminum matrix around Si‐phase compounds, and the dissolution was more remarkable at lower NaCl concentrations. Mass loss of the specimens after the 604.8‐ks immersion was also higher at lower NaCl concentrations. In the repeated wet–dry cycle tests, a 20 mm3 droplet of 0.2–5.5 kmol/m3 NaCl solution was initially dripped on the specimens, and left for 690 s to allow the drying up of the droplet, resulting in solid NaCl precipitation. Then, the dissolution and precipitation of NaCl were repeated a further 149 times by dripping 20‐mm3 pure water at 690‐s intervals. The specimens after the 150 cycles showed different corrosion modes at the center and edge of the droplets. At the edge, 40–80 × 10−6 pits/m2 of 20–50 µm diameter had formed, showing more corrosion with higher NaCl concentration droplets, and at the droplet center, the corrosion showed preferential dissolution of the aluminum matrix around the Si‐phases, similar to the situation in the immersion tests. Copyright © 2015 John Wiley & Sons, Ltd.
A game theory‐inspired channel allocation policy for multi‐radio pervasive ad hoc communications
Authors: Chiti Francesco , Fantacci Romano , Düzgün Fatma Gamze , Vespri Vincenzo
Published: December 2015

The impressive increase of innovative wireless communication technologies and applications represents nowadays a key approach to enable pervasive communications environments. In particular, the emerging paradigms of the Internet of Things and capillary networks offer effective ways to make devices connected. This has triggered the development of effective methodologies and procedures to allow an unlimited number of devices to exchange information mainly in an autonomous mode. However, it is a well‐known concept that wireless networks capacity usually decreases with the number of nodes. In particular, in order to improve the throughput scalability, a promising approach is that of resorting to the use of multiple radio interfaces at each node, in order to exploit spatial reuse of frequencies. Towards this end, game theory methodologies offer efficient approaches to solve the complex radio interfaces selection and allocation problems. This paper proposes a game theory‐inspired approach to efficiently select the number of radio interfaces to be used at each node site in order to lower the energy consumption and maximise the end‐to‐end throughput of any communication on which the node is involved in. The good behaviour of the proposed approach is validated by provided theoretical framework and numerical results derived by considering different data packets wireless forwarding schemes. Copyright © 2015 John Wiley & Sons, Ltd.
Investigation of the Catalytic Activity of a 2‐Phenylidenepyridine Palladium(II) Complex Bearing 4,5‐Dicyano‐1,3‐bis(mesityl)imidazol‐2‐ylidene in the Mizoroki‐Heck Reaction
Authors: Baier Heiko , Kelling Alexandra , Schilde Uwe , Holdt Hans‐Jürgen
Published: December 2015

The phenylidenepyridine (ppy) palladacycles [PdCl(ppy)(IMes)] (4) [IMes = 1,3‐bis(mesityl)imidazol‐2‐ylidene] and [PdCl(ppy){(CN)2IMes}] (6) [(CN)2IMes = 4,5‐dicyano‐1,3‐bis(mesityl)imidazol‐2‐ylidene] were prepared by facile two step syntheses, starting with the reaction of palladium(II) chloride with 2‐phenylpyridine followed by subsequent addition of the NHC ligand to the precatalyst precursor [PdCl(ppy)]2. Suitable crystals for the X‐ray analysis of the complexes 4 and 6 were obtained. It was shown that 6 has a shorter NHC‐palladium bond than the IMes complex 4. The difference of the palladium carbene bond lengths based on the higher π‐acceptor strength of (CN)2IMes in comparison to IMes. Thus, (CN)2IMes should stabilize the catalytically active central palladium atom better than IMes. As a measure for the π‐acceptor strength of (CN)2IMes compared to IMes, the selone (CN)2IMes·Se (7) was prepared and characterized by 77Se‐NMR spectroscopy. The π‐acceptor strength of 7 was illuminated by the shift of its 77Se‐NMR signal. The 77Se‐NMR signal of 7 was shifted to much higher frequencies than the 77Se‐NMR signal of IMes·Se. Catalytic experiments using the Mizoroki‐Heck reaction of aryl chlorides with n‐butyl acrylate showed that 6 is the superior performer in comparison to 4. Using complex 6, an extensive substrate screening of 26 different aryl bromides with n‐butyl acrylate was performed. Complex 6 is a suitable precatalyst for para‐substituted aryl bromides. The catalytically active species was identified by mercury poisoning experiments to be palladium nanoparticles.
Elevated C-reactive protein levels in schizophrenia inpatients is associated with aggressive behavior
Authors: Barzilay R. , Lobel T. , Krivoy A. , Shlosberg D. , Weizman A. , Katz N.
Published: December 2015

Background

An association between inflammation and behavioral domains of mental disorders is of growing interest. Recent studies reported an association between aggression and inflammation. In this study, we investigated the association between aggressive behavior and inflammatory markers in schizophrenia inpatients.

Methods

Adult schizophrenia inpatients without affective symptoms (n = 213) were retrospectively identified and categorized according to their C-reactive protein measurement at admission as either elevated (CRP > 1 mg/dL; n = 57) or normal (CRP < 1 mg/dL; n = 156). The following indicators of aggression were compared: PANSS excitement component (PANSS-EC), restraints and suicidal behavior during hospitalization. Univariate comparisons between elevated and normal CRP levels were performed and multivariate analysis was conducted to control for relevant covariates.

Results

CRP levels significantly correlated with other laboratory markers indicating increased inflammation including leukocyte count and neutrophil to lymphocyte ratio (r = 0.387, P < 0.0001 and r = 0.356, P < 0.0001) respectively. Inpatients with elevated C-reactive protein displayed increased aggressive behavior compared to patients with normal CRP levels (<1 mg/dL). This was manifested by higher rates of restraint during hospitalization (χ2 = 5.22, P = 0.031) and increased PANSS-EC score (U = 5410.5, P = 0.012). Elevated CRP levels were not associated with suicidal behavior. Multivariate analysis revealed that higher PANSS-EC score was associated with elevated CRP after controlling for the covariates age, sex, BMI and smoking.

Conclusion

This study identified a potential biological correlate (inflammation) of a specific behavioral endophenotype (aggression) in schizophrenia inpatients.
Keep at bay! – Abnormal personal space regulation as marker of paranoia in schizophrenia
Authors: Schoretsanitis G. , Kutynia A. , Stegmayer K. , Strik W. , Walther S.
Published: December 2015

Background

During threat, interpersonal distance is deliberately increased. Personal space regulation is related to amygdala function and altered in schizophrenia, but it remains unknown whether it is particularly associated with paranoid threat.

Methods

We compared performance in two tests on personal space between 64 patients with schizophrenia spectrum disorders and 24 matched controls. Patients were stratified in those with paranoid threat, neutral affect or paranoid experience of power. In the stop-distance paradigm, participants indicated the minimum tolerable interpersonal distance. In the fixed-distance paradigm, they indicated the level of comfort at fixed interpersonal distances.

Results

Paranoid threat increased interpersonal distance two-fold in the stop-distance paradigm, and reduced comfort ratings in the fixed-distance paradigm. In contrast, patients experiencing paranoid power had high comfort ratings at any distance. Patients with neutral affect did not differ from controls in the stop-distance paradigm. Differences between groups remained when controlling for gender and positive symptom severity. Among schizophrenia patients, the stop-distance paradigm detected paranoid threat with 93% sensitivity and 83% specificity.

Conclusions

Personal space regulation is not generally altered in schizophrenia. However, state paranoid experience has distinct contributions to personal space regulation. Subjects experiencing current paranoid threat share increased safety-seeking behavior.
Hostility in schizophrenia: An integrated analysis of the combined Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and the European First Episode Schizophrenia Trial (EUFEST) studies
Authors: Volavka J. , Van Dorn R.A. , Citrome L , Kahn R.S. , Fleischhacker W.W. , Czobor P.
Published: December 2015

Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study enrolled a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) enrolled 498 patients. We have combined these two samples to study the effects of hostility on study discontinuation as well as to examine correlates and predictors of hostility. Individual data from 1154 patients with complete data were used for analyses. Survival analysis demonstrated that higher hostility was associated with earlier all-cause treatment discontinuation. Furthermore, regression analysis indicated that increased hostility was associated with more severe positive symptoms, lower adherence to pharmacological treatment, younger age, impaired insight, and more drug or alcohol consumption. The clinical implications of the results point to the importance of establishing therapeutic alliance while managing patient's symptoms of hostility with antipsychotics such as olanzapine combined with psychosocial interventions to improve insight and reduce substance use.