bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of the Kyoto Protocol on Carbon Emissions
Authors: Aichele Rahel , Felbermayr Gabriel
Published: August 2013

Since 1997, CO2 emissions have continued to rise in many countries despite their emission caps under the Kyoto Protocol (Kyoto). Failure to meet promised targets, however, does not imply that Kyoto has been pointless. Whether Kyoto has made a difference relative to the counterfactual of “No Kyoto” is an empirical question that requires an instrumental variables strategy. We argue that countries’ ratification of the statutes governing the International Criminal Court is a valid instrument for ratification of Kyoto commitments. In our panel fixed effects estimations, the instrument easily passes weak identification and overidentification tests. It can be plausibly excluded from our second‐stage equations and does not cause CO2 emissions. Our estimates suggest that Kyoto ratification has a quantitatively large (about 10 percent) and robust, though only moderately statistically significant, negative effect on CO2 emissions. We also show that higher fuel prices and a different energy mix in Kyoto countries support this result.
Long‐term results of the combination of the N7 induction chemotherapy and the busulfan‐melphalan high dose chemotherapy
Authors: Valteau‐Couanet Dominique , Le Deley Marie‐Cécile , Bergeron Christophe , Ducassou Stéphane , Michon Jean , Rubie Hervé , Le Teuff Gwenael , Coze Carole , Plantaz Dominique , Sirvent Nicolas , Bouzy Jeanine , Chastagner Pascal , Hartmann Olivier
Published: August 2013

Background

To evaluate long‐term survival of the first cohort of stage‐4 neuroblastoma patients treated with the N7 induction chemotherapy, surgery of the primary tumor and high‐dose chemotherapy (HDC) containing Busulfan–Melphalan (Bu‐Mel) followed by autologous stem cell transplantation (ASCT).

Procedure

From 1998 to 1999, 47 children were included in the NB97 trial and treated with induction chemotherapy according to the N7 protocol, followed by surgery of the primary tumor. HDC (Busulfan, 600 mg/m2 Melphalan, 140 mg/m2) was administered in patients with partial response of metastases with no more than 3 mIBG spots. Radiotherapy was delivered to the primary tumor site when tumors displayed MYCN amplification.

Results

Thirty‐nine patients received Bu‐Mel (83%): 23 who had achieved complete response (CR) of metastases, 20 after induction treatment and 3 after second‐line chemotherapy, and 16 in partial response (PR). The toxicity of the whole treatment was manageable. The main HDC related‐toxicity was hepatic veno‐occlusive disease grade > 2 occurring in 15% of the patients. The 8‐year EFS of the whole cohort was 34% (95% CI, 22–48%). The 8‐year EFS of the 39 patients who received Bu‐Mel and ASCT was 41% (95% CI, 27–57%). Patients who achieved a CR of metastases at the end of induction chemotherapy had a significantly better outcome than the others (8‐year EFS, 52% vs. 20%; P = 0.02).

Conclusions

The long‐term results of this first prospective cohort of patients with metastatic disease treated with the N7 induction chemotherapy and HDC (Bu‐Mel) confirm published data with stable survival curves but with a longer follow‐up. Pediatr Blood Cancer 2014;61:977–981. © 2013 Wiley Periodicals, Inc.
Dynamic mechanical analysis and morphological studies of fly ash/mica reinforced poly(ether‐ether‐ketone)‐based hybrid composites
Authors: Rahail Parvaiz M. , Thorat P.V. , Mahanwar P.A.
Published: August 2013

Hybrid composites based on poly(ether‐ether‐ketone) (PEEK) were fabricated with fly ash and mica. Nearly 5, 10, and 15 wt% of fly ash were replaced by mica of the optimized fly ash reinforced composites and were subjected to dynamical mechanical analysis to determine the dynamic properties as a function of temperature. The storage modulus E′ was found to decrease with the increase of weight fraction of mica. Loss modulus was also found to decrease with loading while the damping property was found to increase marginally. Peak height of tan δ for hybrid composites were decreased by varying combinations of fly ash with mica. It is probably due to improved crystallinity of PEEK and strong interaction between the fillers and PEEK matrix. Cole–Cole analysis was made to understand the phase behavior of the composite samples. Kubat parameter was calculated to study the adhesion between matrix and filler of the fabricated composites. Without surface modification for inorganic fillers, the distribution of two different shape filler particles appears to be reasonably uniform. The use and limitation of various theoretical equations to predict the tan δ and storage modulus of filler reinforced composites have been discussed. Addition of both fillers opens up new opportunities for development of high‐performance multifunctional materials suitable for industrial applications. Scanning electron micrographs of tensile fracture surfaces of composites demonstrated filler–matrix bonding. POLYM. COMPOS., 35:68–78, 2014. © 2013 Society of Plastics Engineers
Cost‐effective manufacturing process for the development of automotive from energy efficient composite materials and sandwich structures
Authors: Khan Laraib Alam , Mahmood Ali Hasan , Hassan Bilal , Sharif Tahir , Khushnod Shahaab , Khan Zaffar M.
Published: August 2013

The advanced composite materials are increasingly being used in the automotives for their ultralight physical properties and super strong mechanical properties. This research examines the cost‐effective single‐step liquid resin infusion manufacturing process for developing all composite car body as the generally used sheet molding compound manufacturing process is highly capital intensive. Three different scaled down models of the Eco car were developed focusing on minimal weight and air drag coupled with aesthetics. Structural design and analysis was carried out using the Pro/E and Ansys tools. The Pro‐E model was scaled up to generate computer‐aided drafting drawings for tool development. Different stations were marked on the model and sliced virtually for development of pattern. Moreover, the mold was manufactured from carbon and glass/polyester composites for prototype manufacturing of the car body. This involved manual placement of desired number of carbon layers as preform on female side of the mold. The vacuum sucked the resin through a number of carefully selected entry ports which ensured effective resin distribution and impregnation. Polycarbonate wind shield was thermoformed in the convection oven according to streamlined geometry of car body and hinged. The car body was integrated with the compatible floor panels and accessories. The crumble zone shock absorber in the bumper was manufactured using successive layers of nomax honeycomb and polyvinyl chloride rigid foam to dampen the accidental shock. The car performed remarkably well in the Eco marathon race held at Malaysia, 35:97–104, 2014. POLYM. COMPOS., 2013. © 2013 Society of Plastics Engineers
2,2,9,9‐Tetramethylcyclonona‐3,5,7‐trienylidene vs. its heterocyclic analogues: A quest for stable carbenes at DFT
Authors: Kassaee Mohammad Zaman , Koohi Maryam , Mohammadi Reza , Ghavami Monireh
Published: August 2013

Replacement of α‐methylenes with BH, AlH, CMe2, SiH2, NH, NMe, NtButyl, NPh, PH, O, and S in non‐planar cyclonona‐3,5,7‐trienylidene (CH2) alters its status from an unstable transition state to rather stable minima, at B3LYP/6‐311++G**//B3LYP/6‐31 + G* levels of theory. All species appear with singlet closed shell (Scs) global minima, except for SiH2 and CH2 which exhibit triplet electronic ground states. The order of stability based on singlet–triplet energy gap (ΔEs–t / kcalmol−1) is: CMe2 (45.8) > NH (35.8) > NMe (32.3) > O (31.5) > NtButyl (27.7) ≥ NPh (27.5) ≥ BH (27.4) > S (21.9) > PH (17.0) > CH2 (−4.4) > SiH2 (−12.5). In contrast to many reports on N‐heterocyclic carbenes, here alkyl groups appear to exert a higher stabilizing effect than heteroatoms, making CMe2 the most stable. In addition bulky NMe, NtButyl, and NPh appear more nucleophilic than their synthesized imidazol‐2‐ylidene congeners. Excluding SiH2, isodesmic reactions reveal that all substituents stabilize singlet state considerably more than the corresponding triplet. Finally, this work is hoped to pave the path for future matrix isolations and IR studies of these rather stable cyclic non‐planar carbenes. Copyright © 2013 John Wiley & Sons, Ltd.
Quantification of seven apolipoproteins in human plasma by proteotypic peptides using fast LC‐MS/MS
Authors: Ceglarek Uta , Dittrich Julia , Becker Susen , Baumann Frank , Kortz Linda , Thiery Joachim
Published: August 2013

Purpose

We investigated different sample pretreatment strategies and developed a standardized sample pretreatment protocol for absolute quantification of seven apolipoproteins (Apos) in human serum by LC‐MS/MS using proteotypic peptides and corresponding stable isotope‐labeled peptides as internal standards.

Experimental design

Micro‐LC was coupled with quadrupole‐linear ion trap MS for quantification and peptide confirmation. Denaturation, reduction, alkylation, and tryptic digestion including ultrasound and microwave assistance were investigated. Method comparison of 50 plasma samples with an immunoassay was performed for Apo A‐I and Apo B.

Results

Tryptic digestion times ranged between 5 min (Apo A‐I, Apo E, Apo A‐IV) and 16 h (Apo A‐II). Ultrasound and microwave assistance did not improve the digestion yield. Linearity was found between 0.1 nmol/L and 100 mmol/L. The lower limits of quantification were ≤0.4 μmol/L for Apo A‐I, Apo A‐IV, Apo B‐100, Apo C‐I, Apo C‐III, Apo E, and <1.4 μmol/L for Apo A‐II. CV <13% were determined. Comparison with immunoassays showed a good agreement for Apo A‐I and Apo B.

Conclusion and clinical relevance

The validated preanalytical protocol enables a reliable simultaneous analysis of seven Apos in human serum without depletion. The method can now be applied in clinical studies to investigate the Apo distributions in cardiovascular diseases.
Clinical applications of capillary electrophoresis coupled to mass spectrometry in biomarker discovery: Focus on bladder cancer
Authors: Latosinska Agnieszka , Frantzi Maria , Vlahou Antonia , Mischak Harald
Published: August 2013

A major requirement in the application of proteins as clinical biomarkers is that they provide a highly sensitive and specific result in disease assessment. Since single biomarkers are generally of limited accuracy, a group or panel of well‐characterized biomarkers appears appropriate, providing a more robust and sensitive MS‐based analytical platform. CE coupled to MS has been successfully used in biomarker discovery and application, as it enables the selective detection of peptides and small proteins, combining the high separation capacity of CE with the advanced sensitivity of MS. CE‐MS allows the characterization of highly complex samples (such as urine, plasma, and other biofluids) in a consistent and reproducible way. It has a range of applications, many focusing especially in studies on urinary peptide biomarkers in kidney and cardiovascular diseases. Another major field of interest has been malignancy of the genitourinary system. In the first part of this review, we cover technical aspects and performance characteristics of CE‐MS, with special focus on the requirements for biomarker discovery and clinical application. In the second part, we review the potential and development of CE‐MS in the management of genitourinary cancers, especially bladder cancer. CE‐MS has been employed in several studies aimed at discovering biomarkers for bladder cancer that may be useful in diagnosis, monitoring for recurrence, and prediction of the risk for the muscle‐invasive stage. In the last part of the review, we discuss current challenges and provide an outlook for ongoing and possible future developments.
Protein structure modeling for CASP10 by multiple layers of global optimization
Authors: Joo Keehyoung , Lee Juyong , Sim Sangjin , Lee Sun Young , Lee Kiho , Heo Seungryong , Lee In‐Ho , Lee Sung Jong , Lee Jooyoung
Published: August 2013

In the template‐based modeling (TBM) category of CASP10 experiment, we introduced a new protocol called protein modeling system (PMS) to generate accurate protein structures in terms of side‐chains as well as backbone trace. In the new protocol, a global optimization algorithm, called conformational space annealing (CSA), is applied to the three layers of TBM procedure: multiple sequence‐structure alignment, 3D chain building, and side‐chain re‐modeling. For 3D chain building, we developed a new energy function which includes new distance restraint terms of Lorentzian type (derived from multiple templates), and new energy terms that combine (physical) energy terms such as dynamic fragment assembly (DFA) energy, DFIRE statistical potential energy, hydrogen bonding term, etc. These physical energy terms are expected to guide the structure modeling especially for loop regions where no template structures are available. In addition, we developed a new quality assessment method based on random forest machine learning algorithm to screen templates, multiple alignments, and final models. For TBM targets of CASP10, we find that, due to the combination of three stages of CSA global optimizations and quality assessment, the modeling accuracy of PMS improves at each additional stage of the protocol. It is especially noteworthy that the side‐chains of the final PMS models are far more accurate than the models in the intermediate steps. Proteins 2014; 82(Suppl 2):188–195. © 2013 Wiley Periodicals, Inc.
A pragmatic dose‐finding approach using short‐term surrogate efficacy outcomes to evaluate binary efficacy and toxicity outcomes in phase I cancer clinical trials
Authors: Asakawa Takashi , Hamada Chikuma
Published: August 2013

There is a growing need for study designs that can evaluate efficacy and toxicity outcomes simultaneously in phase I or phase I/II cancer clinical trials. Many dose‐finding approaches have been proposed; however, most of these approaches assume binary efficacy and toxicity outcomes, such as dose‐limiting toxicity (DLT), and objective responses. DLTs are often defined for short time periods. In contrast, objective responses are often defined for longer periods because of practical limitations on confirmation and the criteria used to define ‘confirmation’. This means that studies have to be carried out for unacceptably long periods of time. Previous studies have not proposed a satisfactory solution to this specific problem. Furthermore, this problem may be a barrier for practitioners who want to implement notable previous dose‐finding approaches. To cope with this problem, we propose an approach using unconfirmed early responses as the surrogate efficacy outcome for the confirmed outcome. Because it is reasonable to expect moderate positive correlation between the two outcomes and the method replaces the surrogate outcome with the confirmed outcome once it becomes available, the proposed approach can reduce irrelevant dose selection and accumulation of bias. Moreover, it is also expected that it can significantly shorten study duration. Using simulation studies, we demonstrate the positive utility of the proposed approach and provide three variations of it, all of which can be easily implemented with modified likelihood functions and outcome variable definitions. Copyright © 2013 John Wiley & Sons, Ltd.
Evaluation of a revised IASI channel selection for cloudy retrievals with a focus on the Mediterranean basin
Authors: Martinet P. , Lavanant L. , Fourrié N. , Rabier F. , Gambacorta A.
Published: August 2013

The Infrared Atmospheric Sounding Interferometer (IASI) provides 8461 channels in the infrared spectrum. In current numerical weather prediction (NWP) models, it is not feasible to assimilate all channels and it is known that the information content between adjacent channels is redundant. This issue has been addressed in NWP centres by employing a channel selection strategy. The goal of this article is to add new channels to the existing IASI operational channel selection, aimed at improving the data assimilation in cloudy conditions and the simultaneous retrieval of cloud microphysical variables, specifically liquid and ice water contents. Cloudy profiles from the French convective‐scale model Applications of Research to Operations at MEsoscale (AROME) are used in the study to focus on the retrieval of cloud variables over the Mediterranean region. Three channel selection methodologies were evaluated in this study: a statistical approach based on the degrees of freedom of the signal (DFS), a physical method based on the channel spectral sensitivity to the cloud variables and a random selection. To validate the new selections, an idealized framework is used with observing system simulation experiments (OSSE) in the context of one‐dimensional variational retrievals. The current operational IASI selection has already been shown to provide good retrievals of cloud variables. However, all the different channel selections improve the results with small differences in the 1D‐Var retrievals. Based on the physical and DFS methods, the final sets of 134 channels sensitive to cloud variables are proposed for future investigation in operational implementation. Additional tests on temperature and water‐vapour retrieval results, air‐mass dependence and cloud microphysical parametrization have also been conducted.
A local joint fast handoff scheme in cognitive wireless mesh networks
Authors: He Yuan , Xu Li , Wu Wei
Published: August 2013

A cognitive wireless mesh (CogMesh) network can provide network access for users (mesh clients) while holding the open spectrum‐sharing feature. It combines the advantages of both cognitive radio networks and wireless mesh networks: high utilization of the scarce radio spectrum, ease of deployment, maintenance, and low cost. However, the unstable radio environment incurs more handoffs in CogMesh than other wireless networks. Therefore, seamless handoff and a lightweight re‐authentication process are required to achieve a high quality of real‐time applications and low network load caused by re‐authentication. In this paper, we introduce a local joint fast handoff scheme based on proxy signature, which is suitable for CogMesh scenarios. After the mutual authentication between a mesh client and a mesh router, a session tunnel key is derived and shared between them to protect their sessions. Because the proxy signature is used, the IEEE 802.1x authentication architecture remains the same, and there is no need for the authentication server to be involved in the handoff procedure, the re‐authentication delay has been reduced, and the load of CogMesh and the authentication server are lower. Copyright © 2013 John Wiley & Sons, Ltd.
Estimating the loss in expectation of life due to cancer using flexible parametric survival models
Authors: Andersson Therese M‐L , Dickman Paul W. , Eloranta Sandra , Lambe Mats , Lambert Paul C.
Published: August 2013

A useful summary measure for survival data is the expectation of life, which is calculated by obtaining the area under a survival curve. The loss in expectation of life due to a certain type of cancer is the difference between the expectation of life in the general population and the expectation of life among the cancer patients. This measure is used little in practice as its estimation generally requires extrapolation of both the expected and observed survival. A parametric distribution can be used for extrapolation of the observed survival, but it is difficult to find a distribution that captures the underlying shape of the survival function after the end of follow‐up. In this paper, we base our extrapolation on relative survival, because it is more stable and reliable. Relative survival is defined as the observed survival divided by the expected survival, and the mortality analogue is excess mortality. Approaches have been suggested for extrapolation of relative survival within life‐table data, by assuming that the excess mortality has reached zero (statistical cure) or has stabilized to a constant. We propose the use of flexible parametric survival models for relative survival, which enables estimating the loss in expectation of life on individual level data by making these assumptions or by extrapolating the estimated linear trend at the end of follow‐up. We have evaluated the extrapolation from this model using data on four types of cancer, and the results agree well with observed data. Copyright © 2013 John Wiley & Sons, Ltd.
Group sequential designs for three‐arm ‘gold standard’ non‐inferiority trials with fixed margin
Authors: Schlömer Patrick , Brannath Werner
Published: August 2013

In the recent years there have been numerous publications on the design and the analysis of three‐arm ‘gold standard’ noninferiority trials. Whenever feasible, regulatory authorities recommend the use of such three‐arm designs including a test treatment, an active control, and a placebo. Nevertheless, it is desirable in many respects, for example, ethical reasons, to keep the placebo group size as small as possible.

We first give a short overview on the fixed sample size design of a three‐arm noninferiority trial with normally distributed outcomes and a fixed noninferiority margin. An optimal single stage design is derived that should serve as a benchmark for the group sequential designs proposed in the main part of this work. It turns out, that the number of patients allocated to placebo is substantially low for the optimal design.

Subsequently, approaches for group sequential designs aiming to further reduce the expected sample sizes are presented. By means of choosing different rejection boundaries for the respective null hypotheses, we obtain designs with quite different operating characteristics. We illustrate the approaches via numerical calculations and a comparison with the optimal single stage design. Furthermore, we derive approximately optimal boundaries for different goals, for example, to reduce the overall average sample size. The results show that the implementation of a group sequential design further improves the optimal single stage design. Besides cost and time savings, the possible early termination of the placebo arm is a key advantage that could help to overcome ethical concerns. Copyright © 2013 John Wiley & Sons, Ltd.
Brief Report: Reconstruction of Joint Hyaline Cartilage by Autologous Progenitor Cells Derived from Ear Elastic Cartilage
Authors: Mizuno Mitsuru , Kobayashi Shinji , Takebe Takanori , Kan Hiroomi , Yabuki Yuichiro , Matsuzaki Takahisa , Yoshikawa Hiroshi Y. , Nakabayashi Seiichiro , Ik Lee Jeong , Maegawa Jiro , Taniguchi Hideki
Published: August 2013

In healthy joints, hyaline cartilage covering the joint surfaces of bones provides cushioning due to its unique mechanical properties. However, because of its limited regenerative capacity, age- and sports-related injuries to this tissue may lead to degenerative arthropathies, prompting researchers to investigate a variety of cell sources. We recently succeeded in isolating human cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor cells have high chondrogenic and proliferative potential to form elastic cartilage with long-term tissue maintenance. However, it is unknown whether ear-derived cartilage progenitor cells can be used to reconstruct hyaline cartilage, which has different mechanical and histological properties from elastic cartilage. In our efforts to develop foundational technologies for joint hyaline cartilage repair and reconstruction, we conducted this study to obtain an answer to this question. We created an experimental canine model of knee joint cartilage damage, transplanted ear-derived autologous cartilage progenitor cells. The reconstructed cartilage was rich in proteoglycans and showed unique histological characteristics similar to joint hyaline cartilage. In addition, mechanical properties of the reconstructed tissues were higher than those of ear cartilage and equal to those of joint hyaline cartilage. This study suggested that joint hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells. It also demonstrated that ear-derived cartilage progenitor cells, which can be harvested by a minimally invasive method, would be useful for reconstructing joint hyaline cartilage in patients with degenerative arthropathies. Stem Cells  2014;32:816–821
Connectives
Authors: Crosson Amy C. , Lesaux Nonie K.
Published: August 2013

Connectives (e.g., although, consequently, in contrast) are often considered the “signposts” of texts. In this article we argue that connectives represent a special kind of vocabulary knowledge that students need to develop both in order to read challenging, academic texts with understanding and to produce academic writing. Yet tapping the meaning of connectives to support comprehension and academic writing may be especially difficult for some students, especially English‐language learners. In this article, we address how and why to provide instruction about connectives to students in the middle grades. Our research with students in fifth grade suggests that young adolescent learners will benefit from explicit instruction about the meanings and roles of connectives, but that this instruction—while direct—should be provided within engaging, meaningful contexts. Examples of instructional practices illustrating how educators can teach about connectives are presented.
Pseudo‐3D RSSI‐based WSN localization algorithm using linear regression
Authors: Vanheel Frank , Verhaevert Jo , Laermans Eric , Moerman Ingrid , Demeester Piet
Published: August 2013

Receiver Strength Signal Indication based Wireless Sensor Networks offer a cheap solution for location‐aware applications. For a final breakthrough these systems need fast deployment and easy auto‐configuration. In this study, we use the real‐life iMinds test bed to expand a two‐dimensional localization algorithm to the pseudo third dimension with very low additional computational time. Our experiments show that this fast three‐dimensional algorithm has no outliers and avoids manual calibration. Our algorithm has lower position errors than a maximum likelihood algorithm with a mean square error cost function. Furthermore, with non‐parametric statistical tests, we show that our previously designed two‐dimensional preprocessing performs equally well in pseudo‐three dimensions: the preprocessing reduces the position error in a statistically significant way.Copyright © 2013 John Wiley & Sons, Ltd.
Brazilian sugarcane ethanol: developments so far and challenges for the future
Authors: Walter Arnaldo , Galdos Marcelo Valadares , Scarpare Fabio Vale , Leal Manoel Regis Lima Verde , Seabra Joaquim Eugênio Abel , da Cunha Marcelo Pereira , Picoli Michelle Cristina Araujo , de Oliveira Camila Ortolan Fernandes
Published: August 2013

Sugarcane ethanol has been produced in Brazil since the early 20th century, but production increased in the mid‐1970s aiming at substituting 20% of the gasoline. Despite an increase in the 2000s production has been stable since 2008. This paper presents a review of the main developments achieved and future challenges. The sector has had positive economic and environmental results through technological development, as a result of research and development by private companies and strong public support. Sugarcane yield has steadily increased and positively impacted production costs, primarily due to better agronomic practices and breeding programs. Owing to environmental and economic reasons, there are on‐going programs to phase out burning, with the gradual replacement of manual harvest with burning by unburnt mechanised harvest. Important agronomic impacts are expected, caused by the large amount of straw left on the soil surface, which also represents a significant bioenergy potential. The sugarcane industry in Brazil has taken advantage of the combined production of sugar and ethanol, and, recently, many mills have enlarged their revenues with surplus electricity. The current efforts for diversification aim at ethanol production through hydrolysis of sugarcane residues and the development of chemical routes. From an environmental point of view, impacts related to land use change are expected on greenhouse emissions, water resources, and biodiversity. Ethanol production is likely to expand in Brazil due to the potential size of the domestic market and to the opportunities for exporting, but this will occur in a context of different and new challenges.WIREs Energy Environ2014, 3:70–92. doi: 10.1002/wene.87

This article is categorized under:

Bioenergy > Economics and Policy

Bioenergy > Systems and Infrastructure

Bioenergy > Climate and Environment
The First Neutral Dinuclear Vanadium Complex Comprising VO and VO2 Cores: Synthesis, Structure, Electrochemical Properties, and Catalytic Activity
Authors: Hosseini‐Monfared Hassan , Bikas Rahman , Mahboubi‐Anarjan Parisa , Weng Ng Seik , Tiekink Edward R. T.
Published: August 2013

A neutral dinuclear vanadium complex containing both oxido and dioxidovanadium cores with hydrazone based ligand, [VO(OCH3)(CH3OH)(HL)VO2] (1) {H4L = bis[(E)‐N′‐(5‐bromo‐2‐hydroxybenzylidene)]‐carbohydrazide}, was synthesized and fully characterized by X‐ray crystallography and spectroscopic methods (IR, UV/Vis, NMR). The ligand acts as a trinegative hexadentate N3O3 donor ligand to form a dinuclear complex and during the reaction V4+ is oxidized to V5+. The coordination polyhedra are a VO5N distorted octahedron for the mono‐oxidovanadium core and a VO3N2 trigonal bipyramid for the dioxidovanadium core. The results of catalytic reactions indicate that 1 is a highly active catalyst in the clean epoxidation reaction of cis‐cyclooctene using aqueous hydrogen peroxide in acetonitrile. Cyclic voltammetric experiments of 1 in DMSO reveal two quasi‐reversible peaks due to the VO3+–VO2+ and VO2+–VO2 couples.
A Novel Stable High‐Nitrogen Energetic Compound: Copper(II) 1,2–Diaminopropane Azide
Authors: Wu Bi‐Dong , Bi Yan‐Gang , Li Fu‐Gang , Yang Li , Zhou Zun‐Ning , Zhang Jian‐Guo , Zhang Tong‐Lai
Published: August 2013

The multi‐ligand coordination compound copper(II) 1,2‐diaminopropane (pn) azide, [Cu(pn)(N3)2]n (1), was synthesized using pn and azido groups. It was characterized by X‐ray single crystal diffraction, elemental analysis, and FT‐IR spectroscopy. The crystal structure of 1 belongs to the monoclinic system, space group C2/c. The copper(II) cation is six‐coordinated by one pn molecule and four azido ligands with μ‐1 and μ‐1,1,3 coordination modes. Thermogravimetric investigations with a heating rate of 10 K·min–1 under nitrogen showed one main exothermic stage with a peak temperature of 215.7 °C in the DSC curve. The non‐isothermal kinetics parameters were calculated by Kissinger and Ozawa methods, respectively. The heat of combustion was measured by oxygen bomb calorimetry, and the enthalpy of formation, the critical temperature of thermal explosion, the entropy of activation (ΔS≠), the enthalpy of activation (ΔH≠), and the free energy of activation (ΔG≠) were calculated. The measurements showed that 1 has very high impact, friction, and flame sensitivities.
Intraoperative Liver Ultrasound Still Affects Surgical Strategy for Patients with Colorectal Metastases in the Modern Era
Authors: Ferrero Alessandro , Langella Serena , Giuliante Felice , Viganò Luca , Vellone Maria , Zimmitti Giuseppe , Ardito Francesco , Nuzzo Gennaro , Capussotti Lorenzo
Published: August 2013

Background

The present study was designed to evaluate the role of intraoperative ultrasound (IOUS) in intrahepatic staging and the impact on surgical strategy for patients with colorectal liver metastases (CRLM).

Methods

The study included 515 patients who had undergone liver resection for CRLM at two tertiary care referral centers. Data from a prospectively collected database were retrospectively analysed. Early intrahepatic recurrence was assessed at 3 and 6 months after resection and was considered as residual disease undetected by IOUS. Performance of imaging modalities was compared by analysis of studies on individual patients.

Results

A total of 1,370 liver metastases were detected preoperatively with a median of 3 imaging modalities. MRI and PET were performed in 51 and 42 % of the patients, respectively. Median number of days between last imaging and surgery was 18. Contrast‐enhanced IOUS was performed in 136 patients (26.4 %). Intraoperatively, 293 new nodules were found in 132 patients: on histology 280 were CRLM (17.6 %). Surgical strategy was changed in 140 patients (27.2 %). On multivariate analysis synchronous and bilobar metastases ≥3 in number, BMI ≥30, and time between last imaging and surgery longer than 18 days resulted in predictive factors indicating new nodules detected by IOUS. Early intrahepatic recurrences were 3.7 and 7.9 % at 3 and 6 months. Performance of CT, MRI, FDG‐PET, and intraoperative staging was compared: sensitivity was 63.6, 68.8, 53.6, and 92 % and specificity was 91, 92.3, 95.8, and 97.8 %, respectively

Conclusions

The use of IOUS continues to be mandatory for correct staging of patients with CRLM undergoing liver resection.
Reduced response of Cystathionine Beta‐Synthase (CBS) to S‐Adenosylmethionine (SAM): Identification and functional analysis of CBS gene mutations in Homocystinuria patients
Authors: Mendes Marisa I. S. , Colaço Henrique G. , Smith Desirée E. C. , Ramos Rúben J. J. F. , Pop Ana , van Dooren Silvy J. M. , Tavares de Almeida Isabel , Kluijtmans Leo A. J. , Janssen Mirian C. H. , Rivera Isabel , Salomons Gajja S. , Leandro Paula , Blom Henk J.
Published: August 2013

A reduced response of cystathionine beta‐synthase (CBS) to its allosteric activator S‐adenosylmethionine (SAM) has been reported to be a cause of CBS dysfunction in homocystinuria patients. In this work we performed a retrospective analysis of fibroblast data from 62 homocystinuria patients and found that 13 of them presented a disturbed SAM activation. Their genotypic background was identified and the corresponding CBS mutant proteins were produced in E. coli. Nine distinct mutations were detected in 22 independent alleles: the novel mutations p.K269del, p.P427L, p.S500L and p.L540Q; and the previously described mutations p.P49L, p.C165Rfs*2, p.I278T, p.R336H and p.D444N. Expression levels and residual enzyme activities, determined in the soluble fraction of E. coli lysates, strongly correlated with the localization of the affected amino acid residue. C‐terminal mutations lead to activities in the range of the wild‐type CBS and to oligomeric forms migrating faster than tetramers, suggesting an abnormal conformation that might be responsible for the lack of SAM activation. Mutations in the catalytic core were associated with low protein expression levels, decreased enzyme activities and a higher content of high molecular mass forms. Furthermore, the absence of SAM activation found in the patients’ fibroblasts was confirmed for all but one of the characterized recombinant proteins (p.P49L). Our study experimentally supports a deficient regulation of CBS by SAM as a frequently found mechanism in CBS deficiency, which should be considered not only as a valuable diagnostic tool but also as a potential target for the development of new therapeutic approaches in classical homocystinuria.
Contribution of histone N‐terminal tails to the structure and stability of nucleosomes
Authors: Iwasaki Wakana , Miya Yuta , Horikoshi Naoki , Osakabe Akihisa , Taguchi Hiroyuki , Tachiwana Hiroaki , Shibata Takehiko , Kagawa Wataru , Kurumizaka Hitoshi
Published: August 2013

Histones are the protein components of the nucleosome, which forms the basic architecture of eukaryotic chromatin. Histones H2A, H2B, H3, and H4 are composed of two common regions, the “histone fold” and the “histone tail”. Many efforts have been focused on the mechanisms by which the post‐translational modifications of histone tails regulate the higher‐order chromatin architecture. On the other hand, previous biochemical studies have suggested that histone tails also affect the structure and stability of the nucleosome core particle itself. However, the precise contributions of each histone tail are unclear. In the present study, we determined the crystal structures of four mutant nucleosomes, in which one of the four histones, H2A, H2B, H3, or H4, lacked the N‐terminal tail. We found that the deletion of the H2B or H3 N‐terminal tail affected histone–DNA interactions and substantially decreased nucleosome stability. These findings provide important information for understanding the complex roles of histone tails in regulating chromatin structure.
Aberrant signalling by protein kinase CK2 in imatinib‐resistant chronic myeloid leukaemia cells: Biochemical evidence and therapeutic perspectives
Authors: Borgo Christian , Cesaro Luca , Salizzato Valentina , Ruzzene Maria , Massimino Maria Lina , Pinna Lorenzo A. , Donella-Deana Arianna
Published: August 2013

Chronic myeloid leukaemia (CML) is driven by the fusion protein Bcr‐Abl, a constitutively active tyrosine kinase playing a crucial role in initiation and maintenance of CML phenotype. Despite the great efficacy of the Bcr‐Abl‐specific inhibitor imatinib, resistance to this drug is recognized as a major problem in CML treatment. We found that in LAMA84 cells, characterized by imatinib‐resistance caused by BCR‐ABL1 gene amplification, the pro‐survival protein kinase CK2 is up‐regulated as compared to the sensitive cells. CK2 exhibits a higher protein‐level and a parallel enhancement of catalytic activity. Consistently, CK2‐catalysed phosphorylation of Akt‐Ser129 is increased. CK2 co‐localizes with Bcr‐Abl in the cytoplasmic fraction as judged by subcellular fractionation and fluorescence immunolocalization. CK2 and Bcr‐Abl are members of the same multi‐protein complex(es) in imatinib‐resistant cells as demonstrated by co‐immunoprecipitation and co‐sedimentation in glycerol gradients. Cell treatment with CX‐4945, a CK2 inhibitor currently in clinical trials, counteracts CK2/Bcr‐Abl interaction and causes cell death by apoptosis. Interestingly, combination of CX‐4945 with imatinib displays a synergistic effect in reducing cell viability. Consistently, knockdown of CK2α expression by siRNA restores the sensitivity of resistant LAMA84 cells to low imatinib concentrations. Remarkably, the CK2/Bcr‐Abl interaction and the sensitization towards imatinib obtained by CK2‐inhibition in LAMA84 is observable also in other imatinib‐resistant CML cell lines.

These results demonstrate that CK2 contributes to strengthen the imatinib‐resistance phenotype of CML cells conferring survival advantage against imatinib. We suggest that CK2 inhibition might be a promising tool for combined strategies in CML therapy.
Urinary Incontinence in Adults With Cerebral Palsy: Prevalence, Type, and Effects on Participation
Authors: Marciniak Christina , O'Shea Sarah A. , Lee Jungwha , Jesselson Michael , Dudas‐Sheehan Diane , Beltran Erik , Gaebler‐Spira Deborah
Published: August 2013

Objective

To assess the prevalence, type, and impact of urinary problems in adults with cerebral palsy and their relation with the Gross Motor Function Classification System for cerebral palsy.

Design

A cross‐sectional prospective survey study.

Setting

An outpatient, urban, academic rehabilitation clinic.

Participants

Ninety‐one adults with cerebral palsy (45 women, 46 men).

Interventions

Subjects were approached at clinic presentation and were interviewed regarding current function, type and incidence of bladder issues, and concerns with bladder problems.

Main Outcome Measures

The International Consultation on Incontinence Questionnaire–Female, or the International Consultation on Incontinence Questionnaire–Male Lower Urinary Tract Symptoms Module, Gross Motor Function Classification System, employment, and type of residence.

Results

The mean age for both women and men was 36 years (range, 18‐79 years). The subjects were currently assessed with the Gross Motor Function Classification System scales I‐V: I, 4.4%; II, 19.8%; III, 13.2%; IV, 40.7%; and V, 22.0%. 95.6% of females and 84.7% of males were living at home. Twenty‐three percent were currently employed. Twenty percent of the women indicated that they had bladder urgency most to all of the time and 46.7% of the women had leakage that occurred 2‐3 times per week to several times per day. In men, urgency that occurred more often than “occasionally” was reported by 45.7%, and 19.6% reported this occurred “most to all of the time.” Multivariable analyses found that obesity compared with normal weight was significantly related to leaking before reaching a toilet (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.3‐14.7), to leaking with cough, exercise, or sneeze (OR 5.6, 95% CI 1.3‐23.1), and to nocturia (OR 5.4, 95% CI 1.2‐25.1). Women were more likely to leak with cough, exercise, or sneeze (OR 5.5, 95% CI 1.5‐20.0). On scales that indicate symptom interference with life, high levels of interference were reported for women with symptoms of leaking and for men with urgency and leaking. No significant differences in living situation or employment were related to incontinence scores for women or men.

Conclusion

There are high levels of incontinence in adults with cerebral palsy, and these individuals report interference with quality of life. Despite these issues, most participants were living in the community, and incontinence scores were not related to employment.
Comparison of Autologous Conditioned Plasma Injection, Extracorporeal Shockwave Therapy, and Conventional Treatment for Plantar Fasciitis: A Randomized Trial
Authors: Chew Kelvin Tai Loon , Leong Darren , Lin Cindy Y. , Lim Kay Kiat , Tan Benedict
Published: August 2013

Objectives

To evaluate the efficacy of autologous conditioned plasma (ACP) compared with extracorporeal shockwave (ESWT) and conventional treatments for plantar fasciitis.

Design

Randomized trial.

Setting

Sports medicine center in a tertiary care hospital.

Patients

Fifty‐four subjects (age range, 29‐71 years) with unilateral chronic plantar fasciitis with more than 4 months of symptoms.

Methods

Subjects randomized to 3 groups: 19 to ACP and conventional treatment (ACP group), 19 to ESWT and conventional treatment (ESWT group), and 16 to conventional treatment alone. Conventional treatment included stretching exercises and orthotics if indicated.

Main Outcome Measurements

Outcomes were pain‐Visual Analog Scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) ankle‐hindfoot scale, and ultrasound plantar fascia thickness assessed at baseline before treatment and at 1 month, 3 months, and 6 months after treatment.

Results

VAS, AOFAS ankle‐hindfoot scale, and plantar fascia thickness improved in all groups. Significant VAS pain score improvements in the ACP group compared with conventional treatment at month 1 (P = .037) and for the ESWT group compared with conventional treatment at months 1, 3, and 6 (P = .017, P = .022, and P = .042). The AOFAS ankle‐hindfoot scale score improved in the ACP group at months 3 and 6 (P = .004 and P = .013) and, for the ESWT group, at months 1 and 3 (P = .011 and P = .003) compared with conventional treatment. Significant improvements in plantar fascia thickness were seen in the ACP group at months 1 and 3 compared with conventional treatments (P = .015 and P = .014) and at months 3 and 6 compared with the ESWT group (P = .019 and P = .027). No adverse events reported.

Conclusions

Treatment of plantar fasciitis with ACP or ESWT plus conventional treatments resulted in improved pain and functional outcomes compared with conventional treatment alone. There was no significant difference between ACP and ESWT in terms of VAS and AOFAS ankle‐hindfoot scale improvements, although the ACP group demonstrated greater reductions in plantar fascia thickness.
Physical Activity in Community‐Dwelling Stroke Survivors and a Healthy Population Is Not Explained by Motor Function Only
Authors: Danielsson Anna , Meirelles Cristiane , Willen Carin , Sunnerhagen Katharina Stibrant
Published: August 2013

Objectives

To explore the relationship between self‐reporting and physical measures and compare self‐reported physical activity (PA) levels in persons who have had a stroke with self‐reported PA levels in a control population.

Design

Cross‐sectional assessment of a convenience sample of survivors of a stroke living in the community and a population‐based sample from the same community.

Setting

University hospital.

Participants

Seventy persons (48 men and 22 women; average age, 60 years) who had a stroke a mean of 6 years earlier and 141 persons (70 men and 71 women; average age, 59 years) who served as control subjects.

Main Outcome Measurements

The Physical Activity Scale for the Elderly (PASE) was used, and self‐selected and maximum walking speeds were measured. Motor function after stroke was assessed with the Fugl‐Meyer Assessment.

Results

The median Fugl‐Meyer score for motor function in the leg was 29. Mean self‐selected and maximum walking speeds after having a stroke were 1.0 m/s and 1.3 m/s, corresponding to 72% and 65% of control values. A regression model with PASE as the dependent variable and age and walking speed as independent variables explained 29% (P < .001) of the variation in the stroke group. For the control group, age and self‐selected walking speed explained 8% of the variation (P < .01). The mean PASE score in the stroke group was 119, compared with 161 in the control group.

Conclusion

Persons who have experienced a stroke and live in the community are less physically active than the population of the same age who have not had a stroke. However, it appears that factors other than motor impairment have an impact on a person's PA level, because only a low association was found between PA level and motor function, with a large dispersion in PA levels in persons with a history of stroke who were physically well recovered.
Efficacy of Stepping Stones Triple P Plus a Stress Management Adjunct for Parents of Children with an Acquired Brain Injury: The Protocol of a Randomised Controlled Trial
Authors: Brown Felicity Louise , Whittingham Koa , McKinlay Lynne , Boyd Roslyn , Sofronoff Kate
Published: August 2013

Paediatric acquired brain injury (ABI) is the most common cause of acquired disability in childhood. It frequently results in significant personality, cognitive, emotional and behavioural changes, and consequent impairment in independent functioning, education, employment and interpersonal relationships. Additionally, paediatric ABI impacts on the entire family system, with parents commonly reporting significant distress and adjustment difficulties. Despite this, there is currently limited research into effective programmes to support families following their child's ABI. This protocol describes a wait-list randomised controlled trial of a behavioural family intervention plus a parent stress management programme for paediatric ABI. Interventions will be conducted with parents in a group format, aiming to improve child outcomes by improving parenting behaviour and coping. Outcomes assessed will be: (i) child behaviour and emotional outcome as measured by parent and teacher reports; (ii) parental style and confidence; (iii) parental adjustment (stress, anxiety and depression symptoms); (iv) family functioning; (v) parent relationship; and (vi) parent psychological flexibility. Assessments will be via questionnaires conducted pre-, mid- and post- intervention, and at a 6-month follow-up. The theoretical basis, study hypotheses, methods and planned analyses are described.