bluuebunny/crossref_metadata_2025 huggingface dataset:
Ligand‐Assisted, Copper(II) Acetate‐Accelerated Azide–Alkyne Cycloaddition
Authors: Michaels Heather A. , Zhu Lei
Published: September 2011

Polytriazole ligands such as the widely used tris[(1‐benzyl‐1 H‐1,2,3‐triazol‐4‐yl)methyl]amine (TBTA), are shown to assist copper(II) acetate‐mediated azide–alkyne cycloaddition (AAC) reactions that involve nonchelating azides. Tris(2‐{4‐[(dimethylamino)methyl]‐1 H‐1,2,3‐traizol‐1‐yl}ethyl)amine (DTEA) outperforms TBTA in a number of reactions. The satisfactory solubility of DTEA in a wide range of polar and nonpolar solvents, including water and toluene, renders it advantageous under copper(II) acetate‐mediated conditions. The copper(II) acetate‐mediated formation of the three triazolyl groups in a tris(triazolyl)‐based ligand occurs sequentially with an inhibitory effect in the last step. The kinetic investigations of the ligand‐assisted reactions reveal an interesting mechanistic dependence on the relative affinity of azide and alkyne to copper (II). In addition to expanding the scope of the copper(II) acetate‐mediated AAC reactions to include nonchelating azides, this work offers evidence for the mechanistic synergy between the title reaction and the alkyne oxidative homocoupling reaction. The elucidation of the structural details of the polytriazole‐ligand‐bound reactive species in copper(I/II)‐mediated AAC reactions, however, awaits further characterization of the metal coordination chemistry of polytriazole ligands.
Global maximum principle for the forward–backward stochastic optimal control problem with poisson jumps
Authors: Shi Jingtao
Published: September 2011

This paper is concerned with the forward–backward stochastic optimal control problem with Poisson jumps. A necessary condition of optimality in the form of a global maximum principle as well as a sufficient condition of optimality are presented under the assumption that the diffusion and jump coefficients do not contain the control variable, and the control domain need not be convex. The case where there are some state constraints is also discussed. A financial example is discussed to illustrate the application of our result.

Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Consensus of data‐sampled multi‐agent systems with Markovian switching topologies
Authors: Zhao Huanyu , Xu Shengyuan , Yuan Deming
Published: September 2011

This paper studies the consensus problem of data‐sampled multi‐agent systems with Markovian switching topologies. Two different consensus algorithms are considered. By a system transformation, the mean‐square consensus problem of multi‐agent systems is converted into the mean‐square stability problem of Markov jump systems. Necessary and sufficient conditions of mean‐square consensus are obtained. The cone complementary linearization algorithm is used to get the allowable control gain. Simulation examples are given to show the effectiveness of the results.

Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Factor analysis of the Parenting Stress Index‐Short Form with parents of young children with autism spectrum disorders
Authors: Zaidman‐Zait Anat , Mirenda Pat , Zumbo Bruno D. , Georgiades Stelios , Szatmari Peter , Bryson Susan , Fombonne Eric , Roberts Wendy , Smith Isabel , Vaillancourt Tracy , Volden Joanne , Waddell Charlotte , Zwaigenbaum Lonnie , Duku Eric , Thompson Ann ,   the Pathways in ASD Study Team
Published: September 2011

The primary purpose of this study was to examine the underlying factor structure of the Parenting Stress Index‐Short Form (PSI‐SF) in a large cohort of parents of young children with autism spectrum disorder (ASD). A secondary goal was to examine relationships between PSI‐SF factors and autism severity, child behavior problems, and parental mental health variables that have been shown to be related to parental stress in previous research. A confirmatory factor analysis (CFA) was used to examine the three‐factor structure described in the PSI‐SF manual [Abidin, 1995]: parental distress, parent–child dysfunctional interaction, and difficult child. Results of the CFA indicated that the three‐factor structure was unacceptable when applied to the study sample. Thus, an exploratory factor analysis was conducted and suggested a six‐factor model as the best alternative for the PSI‐SF index. Spearman's correlations revealed significant positive correlations with moderate to large effect sizes between the revised PSI‐SF factors and autism severity, externalizing and internalizing child behaviors, and an index of parent mental health. The revised factors represent more narrowly defined aspects of the three original subscales of the PSI‐SF and might prove to be advantageous in both research and clinical applications. Autism Res 2011,4:336–346. © 2011 International Society for Autism Research, Wiley Periodicals, Inc.
What is the impact of autism on mother–child interactions within families with a child with autism spectrum disorder?
Authors: Meirsschaut Mieke , Warreyn Petra , Roeyers Herbert
Published: September 2011

This within‐family study investigated whether mothers differentiate between children in their interactive behavior. Mothers were observed during a play and a task interaction separately with their child with autism spectrum disorder (ASD) (between 46 and 84 months old, M = 68) and with a younger sibling (between 29 and 67 months old, M = 48). Additionally, the social behavior of the children with ASD and their non‐ASD siblings was compared. Results show that mothers differentiated in their responsiveness but not in their initiatives toward the children. Children with ASD and their non‐ASD siblings were equally responsive but children with ASD were more imperative toward their caregiver. Several interpretations of these findings are discussed. Finally, it is concluded that family‐based interventions will benefit from a better understanding of the effect of ASD on mother–child interactions within families with a child with ASD. Therefore, between‐family studies should be complemented with within‐family studies. Autism Res 2011,4:358–367. © 2011 International Society for Autism Research, Wiley Periodicals, Inc.
Outcomes following surgery for colorectal cancer with synchronous peritoneal metastases
Authors: Mulsow J , Merkel S , Agaimy A , Hohenberger W
Published: September 2011

Background

The optimal treatment of peritoneal carcinomatosis of colorectal origin appears to be a combination of systemic chemotherapy and complete surgical cytoreduction with synchronous intraperitoneal chemotherapy. The aim of this study was to assess the feasibility of, and outcomes following, surgical treatment and systemic chemotherapy alone.

Methods

Prospectively collated data from the Erlangen Registry for Colorectal Cancer were analysed for patients presenting with peritoneal carcinomatosis of colorectal origin between 1990 and 2006. Operative and adjuvant treatment, along with details of postoperative morbidity, were evaluated and correlated with survival outcomes after 5 years.

Results

Some 125 patients underwent surgical resection for colorectal cancer and synchronous peritoneal carcinomatosis. Two-thirds also had non-peritoneal distant metastases. R0/R1 resection was possible in 24 (59 per cent) of 41 patients with peritoneal metastases alone, and in a further seven patients with both peritoneal and distant metastases (overall R0/R1 resection rate 24·8 per cent). In-hospital morbidity and mortality rates were 32·0 and 12·0 per cent respectively. Twenty-three of the 31 patients who underwent R0/R1 resection developed recurrent disease. Median survival for the entire group was 12 months. Following R0/R1 resection median survival was 25 months and the 5-year survival rate 22 per cent. Six (4·8 per cent) of the 125 patients survived for more than 5 years.

Conclusion

Complete resection of all metastatic disease was associated with improved survival and was possible in almost 60 per cent of patients with peritoneal metastases alone.
Protein recovery from surfactant precipitation
Authors: Cheng Shu Ian , Stuckey David C.
Published: September 2011

The recovery of lysozyme from an aqueous solution containing precipitated lysozyme‐AOT complexes formed by the direct addition of sodium bis‐(2‐ethylhexyl) sulfosuccinate (AOT) to a lysozyme solution was studied using both solvents, and a counterionic surfactant. Ethanol, methanol and solvent mixtures dissolved the surfactant precipitate and recovered lysozyme as a solid. Recovery efficiency and protein stability varied with the type of solvent used. An entirely different method of recovery was also evaluated using a counterionic surfactant: trioctylmethylammonium chloride (TOMAC) which bound to AOT releasing lysozyme into solution. Complete recovery (100%) of lysozyme was achieved at a molar ratio of 2:1 (TOMAC:AOT), and the original protein activity was maintained in the final aqueous phase. The recovered lysozyme retained its secondary structure as observed in circular dichroism (CD) spectra. Specific activity studies show that counterionic surfactant extraction does not alter the biological activity of the enzyme. © 2011 American Institute of Chemical Engineers Biotechnol. Prog.,, 2011
Effect of needle geometry on flow rate and cell damage in the dispensing‐based biofabrication process
Authors: Li Minggan , Tian Xiaoyu , Schreyer David J. , Chen Xiongbiao
Published: September 2011

Biodispensing techniques have been widely applied in biofabrication processes to deliver cell suspensions and biomaterials to create cell‐seeded constructs. Under identical operating conditions, two types of dispensing needles—tapered and cylindrical—can result in different flow rates of material and different cell damage percent induced by the mechanical forces. In this work, mathematical models of both flow rate and cell damage percent in biodispensing systems using tapered and cylindrical needles, respectively, were developed, and experiments were carried out to verify the effectiveness of the developed models. Both simulations and experiments show tapered needles produce much higher flow rates under the same pressure conditions than cylindrical needles. Use of a lower pressure in a tapered needle can therefore achieve the same flow rate as that in a cylindrical needle. At equivalent flow rates, cell damage in a tapered needle is lower than that in a cylindrical one. Both Schwann cells and 3T3 fibroblasts, which have been widely used in tissue engineering, were used to validate the cell damage models. Application of the developed models to specify the influence of process parameters, including needle geometry and air pressure, on the flow rate and cell damage percent represents a significant advance for biofabrication processes. The models can be used to optimize process parameters to preserve cell viability and achieve the desired cell distribution in dispensing‐based biofabrication. © 2011 American Institute of Chemical Engineers Biotechnol. Prog.,, 2011
And then there were four: Anatomical observations on the pollical palmar interosseous muscle in humans
Authors: Morrison Peter E. , Hill Robert V.
Published: September 2011

Although anatomists generally agree upon the presence of four interosseous muscles in the human hand, the number and identity of the palmar interosseous muscles remains contentious. Recent studies suggest that a majority of human hands possess four palmar interossei, yet most contemporary texts suggest the presence of only three. The pollical palmar interosseous muscle (PPIM), associated with the first digit, has been alternatively interpreted as a distinct muscle, part of another hand muscle, or nonexistent. We examined 45 hands from 23 human cadavers to investigate the prevalence of this muscle and found it to occur in varying degrees of expression in 91% of specimens. We also tested the hypothesis that the PPIM forms the smaller part of a “parallel muscle combination” and is therefore ideally suited to act as a proprioceptive organ. Results do not show a significantly higher density of muscle spindles in the PPIM relative to the adjacent adductor pollicis, provisionally refuting this hypothesis. The presence of the PPIM, observed in the majority of hands from several populations, indicates that it should be regularly included in mainstream anatomy texts and atlases. Clin. Anat. 24:978–983, 2011. © 2011 Wiley Periodicals, Inc.
Connection between the spinal dura mater and suboccipital musculature: Evidence for the myodural bridge and a route for its dissection—A review
Authors: Kahkeshani Kourosh , Ward Peter J.
Published: September 2011

A connective tissue link between the spinal dura mater and the rectus capitis posterior minor muscle was first described in 1995 and has since been readily demonstrated via dissection, magnetic resonance imaging, and plastinated cross‐sections of the upper cervical region (Hack et al. [1995] Spine 20:2484–2486). This structure, the so‐called “myodural bridge,” has yet to be included in any of the American anatomy textbooks or dissection guides commonly used in medical education. This direct anatomic link between the musculoskeletal system and the dura mater has important ramifications for the treatment of chronic cervicogenic headache. This article summarizes the anatomic and clinical research literature related to this structure and provides a simple approach to dissect the myodural bridge and its attachment to the posterior atlanto‐occipital membrane/spinal dura mater complex and summarizes the case for its possible inclusion in medical anatomy curricula. Clin. Anat. 25:415–422, 2012. © 2011 Wiley Periodicals, Inc.
DLP: A tool to develop technical and soft skills in engineering
Authors: Redoli Judith , Mompó Rafael , de la Mata David , Doctor Miguel
Published: September 2011

This article describes how to develop and implement a tool that enables engineering students to acquire soft‐skills taking advantage of the purely technical engineering educational tasks. Delphi Learning Package (DLP) tool is based on a Delphi strategic consulting method. Generally, this method is used to obtain long‐term forecasts from knowledge of groups of experts. Some adjustments have been made to Delphi method in order to apply it to learning and acquiring soft‐skills in engineering. For instance, this tool can be used to guide students toward obtaining key parameters for a technical matter or to find the best solutions to an intricate multiple‐solution problem. Thus, students will have to use not only knowledge learned on the subject of engineering, but also knowledge resulting from handling‐related documentation. By tackling a multiple‐solution problem, students develop different soft skills such as critical thinking, synthesis ability, inference, and argumentation. In order to judge the value of this tool, two pilot projects have been developed involving fourth year students with a major in Telecommunications Engineering. This tool can be used freely by contacting the authors of this article. © 2011 Wiley Periodicals, Inc. Comput Appl Eng Educ 21:E51–E61, 2013
Definition of the Common and Divergent Steps in Carbapenem β‐Lactam Antibiotic Biosynthesis
Authors: Bodner Micah J. , Li Rongfeng , Phelan Ryan M. , Freeman Michael F. , Moshos Kristos A. , Lloyd Evan P. , Townsend Craig A.
Published: September 2011

Approximately 50 naturally occurring carbapenem β‐lactam antibiotics are known. All but one of these have been isolated from Streptomyces species and are disubstituted structural variants of a simple core that is synthesized by Pectobacterium carotovorum (Erwinia carotovora), a phylogenetically distant plant pathogen. While the biosynthesis of the simple carbapenem, (5R)‐carbapen‐2‐em‐3‐carboxylic acid, is impressively efficient requiring only three enzymes, CarA, CarB and CarC, the formation of thienamycin, one of the former group of metabolites from Streptomyces, is markedly more complex. Despite their phylogenetic separation, bioinformatic analysis of the encoding gene clusters suggests that the two pathways could be related. Here we demonstrate with gene swapping, stereochemical and kinetics experiments that CarB and CarA and their S. cattleya orthologues, ThnE and ThnM, respectively, are functionally and stereochemically equivalent, although their catalytic efficiencies differ. The biosynthetic pathways, therefore, to thienamycin, and likely to the other disubstituted carbapenems, and to the simplest carbapenem, (5R)‐carbapen‐2‐em‐3‐carboxylic acid, are initiated in the same manner, but share only two common steps before diverging.
Percutaneous stent implantation into coronary arteries in infants
Authors: Bratincsák András , Salkini Anas , El‐Said Howaida G. , Moore John W.
Published: September 2011

Objectives: To investigate the feasibility, procedural techniques, safety, and overall potential of percutaneous coronary angioplasty and stent implantation in infants with coronary artery disease and acute coronary syndrome. Background: Despite extensive experience in adult patients, percutaneous coronary intervention remains uncommon in children and extremely rare in infants. Methods: Retrospective review including all children who underwent percutaneous coronary angioplasty in Rady Children's Hospital—San Diego during a period of 4 years. Results: Seven children including four children less than 15 months of age underwent percutaneous coronary intervention with coronary stent implantation in the proximal portion of the left or right coronary arteries. Successful stent placement with excellent revascularization was achieved in all cases. Mean coronary artery diameter was 0.65 mm prior to stent placement. Balloon angioplasty resulted in suboptimal resolution of coronary stenosis, thus bare metal stents were implanted in all cases, dilated to a mean of 2.5‐mm internal diameter. Average intervention‐free period was 434 days after stent implantation. In‐stent re‐stenosis and stent thrombosis did not occur if the implanted stent diameter was greater than 2.5 mm and the patient received dual anti‐platelet therapy. Conclusions: Our experience suggests that coronary artery stent implantation is a feasible and relatively safe palliative option in infants and toddlers with coronary stenosis. It is a viable strategy for bridging patients with acute ischemia or poor ventricular function to elective surgical revascularization or transplantation. © 2011 Wiley Periodicals, Inc.
Tuning of Active Sites in NiNbO Catalysts for the Direct Conversion of Ethane to Acetonitrile or Ethylene
Authors: Rubio‐Marcos Fernando , Rojas Elizabeth , López‐Medina Ricardo , Guerrero‐Pérez M. Olga , Bañares Miguel A. , Fernandez José F.
Published: September 2011

NiO nanoparticles that are highly active for the ethane activation have been prepared. These nanoparticles have been dispersed on the surface of two different Nb2O5 materials by using a novel dry nanodispersion method. This article describes the characterization and catalytic behavior of both series of catalysts as well as the nature of the active sites required for the transformation of ethane into acetonitrile and/or ethylene. It is demonstrated how such active sites present in the catalysts are obtained through this novel dry mixing method. The catalysts obtained are promising catalytic materials for both, ethane ammoxidation and oxidative dehydration (ODH) reactions.
Systematic Synthesis of Inhibitors of the Two First Enzymes of the Bacterial Heptose Biosynthetic Pathway: Towards Antivirulence Molecules Targeting Lipopolysaccharide Biosynthesis
Authors: Durka Maxime , Tikad Abdellatif , Périon Régis , Bosco Michael , Andaloussi Mounir , Floquet Stéphanie , Malacain Elodie , Moreau François , Oxoby Mayalen , Gerusz Vincent , Vincent Stéphane P.
Published: September 2011

L‐Heptoses (L‐glycero‐D‐manno‐heptopyranoses) are constituents of the inner core of lipolysaccharide (LPS), a molecule playing key roles in the mortality of many infectious diseases as well as in the virulence of many human pathogens. The inhibition of the first enzymes of the bacterial heptose biosynthetic pathway is an almost unexplored field to date although it appears to be a very novel way for the development of antivirulence drugs. We report the synthesis of a series of D‐glycero‐D‐manno‐heptopyranose 7‐phosphate (H7P) analogues and their inhibition properties against the isomerase GmhA and the the kinase HldE, the two first enzymes of the bacterial heptose biosynthetic pathway. The heptose structures have been modified at the 1‐, 2‐, 6‐ and 7‐positions to probe the importance of the key structural features of H7P that allow a tight binding to the target enzymes; H7P being the product of GmhA and the substrate of HldE, the second objective was to find structures that could simultaneously inhibit both enzymes. We found that GmhA and HldE were extremely sensitive to structural modifications at the 6‐ and 7‐ positions of the heptose scaffold. To our surprise, the epimeric analogue of H7P displaying a D‐glucopyranose configuration was found to be the best inhibitor of both enzymes but also the only molecule of this series that could inhibit GmhA (IC50=34 μM) and HldE (IC50=9.4 μM) in the low micromolar range. Noteworthy, this study describes the first inhibitors of GmhA ever reported, and paves the way to the design of a second generation of molecules targeting the bacterial virulence.
A Unique Case of Oxidative Addition of Interhalogens IX (X=Cl, Br) to Organodiselone Ligands: Nature of the Chemical Bonding in Asymmetric ISeX Polarised Hypervalent Systems
Authors: Juárez‐Pérez Emilio José , Aragoni M. Carla , Arca Massimiliano , Blake Alexander J. , Devillanova Francesco A. , Garau Alessandra , Isaia Francesco , Lippolis Vito , Núñez Rosario , Pintus Anna , Wilson Claire
Published: September 2011

The reactivity of the imidazoline‐2‐selone derivatives 1,1′‐methylenebis(3‐methyl‐4‐imidazoline‐2‐selone) (D1) and 1,2‐ethylenebis(3‐methyl‐4‐imidazoline‐2‐selone) (D2) towards the interhalogens IBr and ICl has been investigated in the solid state with the aim of synthesising “T‐shaped” hypervalent chalcogen compounds featuring the extremely rare linear asymmetric IEX moieties (E=S, Se; X=Br, Cl). X‐ray diffraction analysis and FT‐Raman measurements provided a clear indication of the presence in the compounds obtained of discrete molecular adducts containing ISeBr and ISeCl hypervalent moieties following a unique oxidative addition of interhalogens IX (X=Cl, Br) to the organoselone ligands. In all asymmetric hypervalent systems isolated, a strong polarisation was observed, with longer bond lengths at the selenium atom involving the most electronegative halogen. A topological electron density analysis on model compounds based on the quantum theory of atoms‐in‐molecules (QTAIM) and electron localisation function (ELF) established the three‐centre–four‐electron (3c–4e) nature of the bonding in these very polarised selenium hypervalent systems and new criteria were suggested to define and ascertain the hypervalency of the selenium atoms in these and related halogen and interhalogen adducts.
Dopant Segregation Analysis on Sb:SnO2 Nanocrystals
Authors: Stroppa Daniel G. , Montoro Luciano A. , Beltrán Armando , Conti Tiago G. , da Silva Rafael O. , Andrés Juan , Leite Edson R. , Ramirez Antonio J.
Published: September 2011

The development of reliable nanostructured devices is intrinsically dependent on the description and manipulation of materials’ properties at the atomic scale. Consequently, several technological advances are dependent on improvements in the characterization techniques and in the models used to describe the properties of nanosized materials as a function of the synthesis parameters. The evaluation of doping element distributions in nanocrystals is directly linked to fundamental aspects that define the properties of the material, such as surface‐energy distribution, nanoparticle shape, and crystal growth mechanism. However, this is still one of the most challenging tasks in the characterization of materials because of the required spatial resolution and other various restrictions from quantitative characterization techniques, such as sample degradation and signal‐to‐noise ratio. This paper addresses the dopant segregation characterization for two antimony‐doped tin oxide (Sb:SnO2) systems, with different Sb doping levels, by the combined use of experimental and simulated high‐resolution transmission electron microscopy (HRTEM) images and surface‐energy ab initio calculations. The applied methodology provided three‐dimensional models with geometrical and compositional information that were demonstrated to be self‐consistent and correspond to the systems’ mean properties. The results evidence that the dopant distribution configuration is dependent on the system composition and that dopant atom redistribution may be an active mechanism for the overall surface‐energy minimization.
Dehydrogenation of Dodecahydro‐N‐ethylcarbazole on Pd/Al2O3 Model Catalysts
Authors: Sobota Marek , Nikiforidis Ioannis , Amende Max , Zanón Beatriz Sanmartín , Staudt Thorsten , Höfert Oliver , Lykhach Yaroslava , Papp Christian , Hieringer Wolfgang , Laurin Mathias , Assenbaum Daniel , Wasserscheid Peter , Steinrück Hans‐Peter , Görling Andreas , Libuda Jörg
Published: September 2011

To elucidate the dehydrogenation mechanism of dodecahydro‐N‐ethylcarbazole (H12‐NEC) on supported Pd catalysts, we have performed a model study under ultra high vacuum (UHV) conditions. H12‐NEC and its final dehydrogenation product, N‐ethylcarbazole (NEC), were deposited by physical vapor deposition (PVD) at temperatures between 120 K and 520 K onto a supported model catalyst, which consisted of Pd nanoparticles grown on a well‐ordered alumina film on NiAl(110). Adsorption and thermally induced surface reactions were followed by infrared reflection absorption spectroscopy (IRAS) and high‐resolution X‐ray photoelectron spectroscopy (HR‐XPS) in combination with density functional theory (DFT) calculations. It was shown that, at 120 K, H12‐NEC adsorbs molecularly both on the Al2O3/NiAl(110) support and on the Pd particles. Initial activation of the molecule occurs through CH bond scission at the 8a‐ and 9a‐positions of the carbazole skeleton at temperatures above 170 K. Dehydrogenation successively proceeds with increasing temperature. Around 350 K, breakage of one CN bond occurs accompanied by further dehydrogenation of the carbon skeleton. The decomposition intermediates reside on the surface up to 500 K. At higher temperatures, further decay to small fragments and atomic species is observed. These species block most of the absorption sites on the Pd particles, but can be oxidatively removed by heating in oxygen at 600 K, fully restoring the original adsorption properties of the model catalyst.
From a Stable Silanone Complex to Isolable, Donor‐Supported Silicoxonium Halides [LSi(dmap)OSiMe3]+X−
Authors: Xiong Yun , Yao Shenglai , Irran Elisabeth , Driess Matthias
Published: September 2011

The first donor‐stabilized silylated silicoxonium species [LSiOSiMe3]+ (L=(RN)C(CH2)CHCMe(NR), R=2,6‐iPr2C6H3) have been synthesized from the reaction of the dmap‐supported (dmap=p‐dimethylaminopyridine) silanone complex [LSi(dmap)O] (1) with trimethylsilyl halides. Although the reaction with Me3SiCl leads directly to the SiO addition product [LSi(Cl)OSiMe3] (2), the ionic silicoxonium bromide [L(dmap)SiOSiMe3]+Br− (3) can be obtained as a primary product of the reaction with Me3SiBr, which affords [LSi(Br)OSiMe3] (4) with release of the dmap ligand at room temperature in THF. In the case of Me3SiI, the reaction furnishes the silicoxonium iodide [L(dmap)SiOSiMe3]+I− (5) as the most stable species. Compounds 2–5 were isolated and fully characterized through multinuclear NMR spectroscopy, mass spectrometry, elemental analyses, and single‐crystal X‐ray diffraction analyses.
Catalyzed Selective Direct α‐ and γ‐Alkylation of Aldehydes with Cyclic Benzyl Ethers by Using T+BF4− in the Presence of an Inexpensive Organic Acid or Anhydride
Authors: Richter Heinrich , Rohlmann Renate , García Mancheño Olga
Published: September 2011

The cross dehydrogenative coupling (CDC) of cyclic benzyl ethers with aliphatic and α,β‐unsaturated aldehydes has been developed. The mild reaction conditions, in which an N‐oxoammonium salt derived from TEMPO (2,2,6,6‐tetramethyl‐1‐piperidinoxyl) is employed as the oxidant in combination with a Cu catalyst, allow the use of relatively redox‐unstable aldehydes under oxidative CDC conditions. The addition of a catalytic amount of trifluoroacetic acid (TFA) or Ac2O facilitates the reaction and increases the efficiency and selectivity. In contrast to the expected α‐alkylation obtained with aliphatic aldehydes, α,β‐unsaturated aldehydes led preferentially to the more challenging γ‐alkylated products. The utility of the developed methodology was demonstrated by the synthesis of isochromane‐derived bioactive compounds, such as the dopamine antagonist sonepiprazole.
Heteroscorpionate Rare‐Earth Metal Zwitterionic Complexes: Syntheses, Characterization, and Heteroselective Catalysis on the Ring‐Opening Polymerization of rac‐Lactide
Authors: Zhang Zhichao , Cui Dongmei
Published: September 2011

Novel neutral phosphine‐modified heteroscorpionate ligand (3,5‐Me2Pz)2CHPPh2 (1) and its derivatives oxophosphine (2) and iminophosphine (3) heteroscorpionates were synthesized for the first time. These neutral heteroscorpionate ligands displayed unique chemistry towards rare‐earth metal tris(alkyl)s [Ln(CH2SiMe3)3(thf)2] (Ln=Y, Lu, Sc). The reaction between compound 1 and [Ln(CH2SiMe3)3(thf)2] afforded heteroscorpionate rare‐earth metal trialkyl adduct complexes 4 a–c. Compounds 2 and 3 were treated with [Ln(CH2SiMe3)3(thf)2] to give the unprecedented zwitterionic heteroscorpionate rare‐earth metal dialkyls 5 and 6, respectively. In the process, the heteroscorpionates transferred to the carbanions by means of methine CH bond cleavage that was attributed to the presence of the electron‐withdrawing groups. In addition the ligand and central metal showed a concerted effect on both the catalytic activity and specific selectivity of complexes 4–6 for the ring‐opening polymerization (ROP) of rac‐lactide (rac‐LA). All the adduct complexes 4 were nonselective and gave atactic polylactide (PLA), probably due to the dissociation of ligand 1 from the active metal center during the polymerization. Strikingly, zwitterionic complexes 5 catalyzed rapid ROP of rac‐LA to produce PLAs with heterotacticity up to 0.87. However, the zwitterionic complexes 6 were less active and less selective than 5, which might be on account of the stronger coordination of the tetradentate ligand. Complexes 5 represent rare examples of the selective ROP of rac‐LA mediated by rare‐earth metal complexes supported by non‐bisphenolate ligands.
A Green and Highly Efficient Protocol for Catalyst‐free Knoevenagel Condensation and Michael Addition of Aromatic Aldehydes with 1,3‐Cyclic Diketones in PEG‐400
Authors: Firouzeh Nemati , Hossein Kiani
Published: September 2011

A convenient, highly efficient and green approach for synthesis of tetraketones from aromatic aldehydes with dimedone and 1,3‐indanedione at room temperature in PEG‐400 is described. The use of PEG‐400 as the reaction medium and avoiding the use of any catalyst makes the process environmentally benign. Seven new compounds are reported.
Three‐Dimensional Entertainment as a Novel Cause of Takotsubo Cardiomyopathy
Authors: Taylor Montoya , Amin Anish , Bush Charles
Published: September 2011

Takotsubo cardiomyopathy (TC) is an uncommon entity. It is known to occur in the setting of extreme catecholamine release and results in left ventricular dysfunction without evidence of angiographically definable coronary artery disease. There have been no published reports of TC occurring with visual stimuli, specifically 3‐dimensional (3D) entertainment. We present a 55‐year‐old woman who presented to her primary care physician's office with extreme palpitations, nausea, vomiting, and malaise <48 hours after watching a 3D action movie at her local theater. Her electrocardiogram demonstrated ST elevations in aVL and V1, prolonged QTc interval, and T‐wave inversions in leads I, II, aVL, and V2‐V6. Coronary angiography revealed angiographically normal vessels, elevated left ventricular filling pressures, and decreased ejection fraction with a pattern of apical ballooning. The presumed final diagnosis was TC, likely due to visual‐auditory–triggered catecholamine release causing impaired coronary microcirculation. © 2011 Wiley Periodicals, Inc.
The volume‐outcome relation in the surgical treatment of esophageal cancer
Authors: Wouters Michel W. J. M. , Gooiker Gea A. , van Sandick Johanna W. , Tollenaar Rob A. E. M.
Published: September 2011

This study was undertaken to conduct a systematic review and meta‐analysis of the literature on the relation between procedural volume and outcome of esophagectomies. A systematic search was carried out to identify articles investigating effects of hospital or surgeon volume on short‐term and long‐term outcomes published between 1995 and 2010. Articles were scrutinized for methodological quality, and after inclusion of only high‐quality studies, a meta‐analysis assuming a random effects model was done to estimate the effect of higher volume on patient outcome. Heterogeneity in study results was evaluated with an I2‐test and risk of publication bias with an Egger regression intercept. Forty‐three studies were found. Sixteen studies met the strict inclusion criteria for the meta‐analysis on hospital volume and postoperative mortality and 4 studies on hospital volume and survival. The pooled estimated effect size was significant for high‐volume providers in the analysis of postoperative mortality (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.89‐2.80) and in the survival analysis (OR, 1.17; 95% CI, 1.05‐1.30). The meta‐analysis of surgical volume and outcome showed no significant results. Studies in which the results were adjusted not only for patient characteristics but also for tumor characteristics and urgency of the operation showed a stronger correlation between hospital volume and mortality. Also, studies performed on data from the United States showed higher effect sizes. The evidence for hospital volume as an important determinant of outcome in esophageal cancer surgery is strong. Concentration of procedures in high‐volume hospitals with a dedicated setting for the treatment of esophageal cancer might lead to an overall improvement in patient outcome. Cancer 2012;. © 2011 American Cancer Society.
Adhesion molecule protein signature in ovarian cancer effusions is prognostic of patient outcome
Authors: Kim Geoffrey , Davidson Ben , Henning Ryan , Wang Junbai , Yu Minshu , Annunziata Christina , Hetland Thea , Kohn Elise C.
Published: September 2011

BACKGROUND:

Ovarian cancer cells in malignant effusions lack attachment to solid‐phase matrix substrata and receive survival stimuli through cell–cell and cell–soluble matrix molecule interactions. We hypothesized that adhesion‐related survival and proliferation pathway signals can inform clinical outcomes and guide targeted therapeutics.

METHODS:

Lysed cell pellets from a blinded set of benign (n = 20) and malignant (n = 51) peritoneal and pleural ovarian cancer patient effusions were applied to reverse‐phase protein arrays and examined using validated antibodies to adhesion‐associated protein endpoints. Results were subjected to hierarchical clustering for signature development. Association between specimen type, protein expression, and clinicopathologic associations were analyzed using the Mann‐Whitney U test. Survival outcomes were estimated using the Kaplan‐Meier method with log‐rank comparison.

RESULTS:

A cell adhesion protein signature obtained from unsupervised clustering distinguished malignant from benign effusions (P = 6.18E‐06). Protein subset analyses from malignant cases defined 3 cell adhesion protein clusters driven by E‐cadherin, epithelial cell adhesion molecule, and N‐cadherin, respectively. The components of the E‐ and N‐cadherin clusters correlated with clinical outcome by Kaplan‐Meier statistics. Univariate analysis indicated that FAK and phosphorylated AKT were associated with higher overall and progression‐free survival (PFS) (P = .03), and Akt, phosphorylated paxillin, and E‐ and N‐cadherin were associated with improved PFS (P ≤ .05). If 4 or 5 of the index adhesion proteins were high, PFS was improved by multivariate analysis (P ≤ .01).

CONCLUSIONS:

This hypothesis‐testing examination of tumor cell adhesion molecules and pathways yielded potential predictive biomarkers with which to triage patients to selected molecular therapeutics and may serve as a platform for biomarker‐based stratification for clinical application. Cancer 2011;. Published 2011 by the American Cancer Society.
A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate‐1 risk myelodysplastic syndrome
Authors: Raza Azra , Galili Naomi , Smith Scott E. , Godwin John , Boccia Ralph V. , Myint Han , Mahadevan Daruka , Mulford Deborah , Rarick Mark , Brown Gail L. , Schaar Dale , Faderl Stefan , Komrokji Rami S. , List Alan F. , Sekeres Mikkael
Published: September 2011

BACKGROUND:

Ezatiostat is a glutathione analog prodrug glutathione S‐transferase P1‐1 (GSTP1‐1) inhibitor. This study evaluated 2 extended dose schedules of oral ezatiostat in 89 heavily pretreated patients with low to intermediate‐1 risk myelodysplastic syndrome (MDS).

METHODS:

Patients were randomized by 1 stratification factor—baseline cytopenia (anemia only vs anemia with additional cytopenias)—to 1 of 2 extended dosing schedules. Multilineage hematologic improvement (HI) responses were assessed by International Working Group 2006 criteria.

RESULTS:

Overall, 11 of 38 (29%) red blood cell (RBC) transfusion‐dependent patients had HI‐Erythroid (HI‐E) response. The median duration of HI‐E response was 34 weeks. Multilineage responses were observed. There was 1 cytogenetic complete response in a del (5q) MDS patient. An important trend was the effect of prior therapy on response. A 40% HI‐E rate (6 of 15 patients) was observed in patients who had prior lenalidomide and no prior hypomethylating agents (HMAs), with 5 of 11 (45%) patients achieving significant RBC transfusion reduction and 3 of 11 (27%) achieving transfusion independence. A 28% HI‐E rate (5 of 18 patients) was observed in patients who were both lenalidomide and HMA naive, with 4 of 8 (50%) patients achieving clinically significant RBC transfusion reductions. Most common ezatiostat‐related adverse events were grade 1 and 2 gastrointestinal including: nausea (45%, 17%), diarrhea (26%, 7%), and vomiting (30%, 12%).

CONCLUSIONS:

Ezatiostat is the first GSTP1‐1 inhibitor shown to cause clinically significant and sustained reduction in RBC transfusions, transfusion independence, and multilineage responses in MDS patients. The tolerability and activity profile of ezatiostat may offer a new treatment option for patients with MDS. Cancer 2012. © 2011 American Cancer Society.
Novel biomarker panel predicts prognosis in human papillomavirus‐negative oropharyngeal cancer
Authors: Wu Yin , Posner Marshall R. , Schumaker Lisa M. , Nikitakis Nikolaos , Goloubeva Olga , Tan Ming , Lu Changwan , Iqbal Sana , Lorch Jochen , Sarlis Nicholas J. , Haddad Robert I. , Cullen Kevin J.
Published: September 2011

BACKGROUND:

New treatment strategies for locally advanced head and neck squamous cell carcinoma combine induction chemotherapy and chemoradiation. Identifying the predictors of outcome in sequentially treated patients is critical for focusing therapeutic research. In this analysis, the authors evaluated human papillomavirus type 16 (HPV‐16) status and the expression levels of a defined set of biomarkers to identify predictors of response to this treatment modality.

METHODS:

In total, 114 patients with oropharyngeal cancer (OPC) who were treated on the TAX 324 trial (cisplatin and fluorouracil with or without docetaxel in patients with locally advanced head and neck squamous cell carcinoma) had pretreatment biopsy specimens that were evaluable for HPV‐16 DNA and immunohistochemical expression of the following biomarkers: beta‐tubulin II (βT‐II), glutathione S‐transferase (GST‐π), p53, and B‐cell lymphoma 2 (Bcl‐2). Patients were categorized into risk groups based on their HPV status and biomarker expression levels.

RESULTS:

Patients with high‐risk OPC were defined by HPV‐negative status and either elevated expression of βT‐II or levels of at least 2 of the other 3 adverse markers (elevated GST‐π, elevated p53, or low Bcl‐2). All other HPV‐negative patients were categorized as moderate risk. In total, 55 patients were HPV‐positive, and 59 patients were HPV‐negative, with 34 were categorized as high risk and 25 categorized as moderate risk. The median survival for HPV‐positive patients was not reached. The median survival was 44.2 months for moderate‐risk patients (95% confidence interval, 20.9 months to not reached) and 12.1 months for high‐risk patients (95% confidence interval, 7.5‐19.7 months). The 24‐month survival rate was 89% for HPV‐positive patients, 67% for moderate‐risk patients, and 29% for high‐risk patients (P < .0001).

CONCLUSIONS:

The molecular data set in this study readily differentiated between 2 distinct groups of patients with locally advanced, HPV‐negative OPC. This risk‐stratification strategy may serve as a guide for treatment selection. Cancer 2012;. © 2011 American Cancer Society.
Association of VEGF and VEGFR2 single nucleotide polymorphisms with hypertension and clinical outcome in metastatic clear cell renal cell carcinoma patients treated with sunitinib
Authors: Kim Jenny J. , Vaziri Susan A.J. , Rini Brian I. , Elson Paul , Garcia Jorge A. , Wirka Robert , Dreicer Robert , Ganapathi Mahrukh K. , Ganapathi Ram
Published: September 2011

PURPOSE:

Biomarkers that predict response or toxicity to antiangiogenic therapy are sought to favorably inform the risk/benefit ratio. This study evaluated the association of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) genetic polymorphisms with the development of hypertension (HTN) and clinical outcome in metastatic clear cell renal cell carcinoma (MCCRCC) patients treated with sunitinib.

PATIENT AND METHODS:

Sixty‐three MCCRCC patients receiving sunitinib (50 mg 4/2) with available blood pressure (BP) data and germline DNA were retrospectively identified. A panel of candidate VEGF and VEGFR2 single nucleotide polymorphisms (SNPs) were evaluated for associations with the development of hypertension and clinical outcome.

RESULTS:

VEGF SNP −634 genotype was associated with the prevalence and duration of sunitinib‐induced hypertension (as defined by systolic pressure ≥150 mmHg and/or diastolic pressure ≥90 mmHg) in both univariable analysis (P = .03 and .01, respectively) and multivariable analysis, which adjusted for baseline BP and use of antihypertension medication (P = .05 and .02, respectively). Patients with the GG genotype were estimated to have a greater likelihood of being hypertensive during treatment compared with patients with the CC genotype (odds ratio of 13.62, 95% confidence interval [CI] 3.71‐50.04). No single VEGF or VEGFR SNPs were found to correlate with clinical outcome. However, the combination of VEGF SNP 936 and VEGFR2 SNP 889 were associated with overall survival after adjustment for prognostic risk group (P = .03).

CONCLUSIONS:

In MCCRCC patients treated with sunitinib, VEGF SNP −634 is associated with hypertension and a combination of VEGF SNP 936 and VEGFR2 SNP 889 genotypes is associated with overall survival. Cancer 2012;. © 2011 American Cancer Society.
National trends in surgical procedures for hepatocellular carcinoma: 1998‐2008
Authors: Nathan Hari , Segev Dorry L. , Mayo Skye C. , Choti Michael A. , Cameron Andrew M. , Wolfgang Christopher L. , Hirose Kenzo , Edil Barish H. , Schulick Richard D. , Pawlik Timothy M.
Published: September 2011

BACKGROUND:

The incidence of hepatocellular carcinoma (HCC) is rising, and the options for surgical therapy of HCC have evolved recently, but use of surgical therapy has not been characterized on a representative, nationwide basis. We quantified trends in use, mortality, and patient and hospital characteristics for 3 surgical therapies for HCC (resection, ablation, and transplantation) in the United States from 1998 to 2008.

METHODS:

Hospital discharge data from the Nationwide Inpatient Sample were used to quantify procedure‐related data for each year. Trends over time were summarized as the average annual percent change (AAPC) and corresponding 95% confidence interval (CI).

RESULTS:

The number of surgical procedures for HCC increased from 1416 to 6769 (AAPC, 13.5%; 95% CI, 10.2%‐16.8%). Volumes increased for all surgical procedures, most notably for ablation (AAPC, 17.3%; 95% CI, 6.6%‐29.2%) and transplantation (AAPC, 20.9%; 95% CI, 14.1%‐28.1%). When analyzed as a proportion of total procedures, there were declines in the relative use of major hepatectomy (35% to 16%; AAPC, −7.2%, 95% CI, −8.8% to −5.6%) and wedge resection (37% to 22%; AAPC, −4.8%; 95% CI, −6.2% to −3.4%), while the proportion accounted for by transplantation increased (16% to 35%; AAPC, 4.4%; 95% CI, 0.2%‐8.9%). Inpatient mortality decreased for each procedure individually and overall from 7.3% to 4.6% (AAPC, −7.7%; 95% CI, −10.8% to −4.5%), despite increasing age and comorbidity burden.

CONCLUSIONS:

The use of surgical therapy for HCC has increased dramatically over the last decade, with a relative shift away from liver resection and toward liver transplantation. These therapeutic modalities must be better targeted to make the most appropriate use of limited health care resources. Cancer 2012;. © 2011 American Cancer Society.
Cytologic and molecular diagnosis of thyroid cancers
Authors: Hassell Lewis A. , Gillies Elizabeth M. , Dunn S. Terence
Published: September 2011

The Bethesda system for standardized reporting of thyroid fine needle aspiration (FNA) cytology has positively affected the clarity of communication of results and management of patients evaluated for thyroid nodules. Problematic areas still exist in the triage of some of these samples, particularly those in the categories of “follicular lesion with atypia of uncertain significance” and “follicular lesion.” The literature on molecular and genetic abnormalities in thyroid lesions is reviewed. Potentially useful markers for distinguishing currently problematic categories of FNA cytologic samples, especially nondiagnostic samples, atypia of uncertain significance, and follicular lesions, are discussed. The predictive value of the respective molecular analyses in these settings is examined. Evaluation of FNA samples with negative or suboptimal follicular cytology for Ras mutations may be useful in detecting potentially significant follicular lesions (carcinomas) but is quite low in overall yield. Cytologic samples with atypia of uncertain significance, which may include the possibility of papillary carcinomas, may be fruitfully evaluated using a panel of molecular tests for BRAF, RET/PTC, PAX8/PPARG1, and Ras. Other markers also have potential utility in the workup of thyroid lesions. An era of combined modality testing in thyroid cytology is emerging in which classical cytologic findings can be coupled with molecular data to increase the predictive power of diagnostic interpretations; however, there remains a group of atypical cytologic samples negative for known molecular markers in which the risk of malignancy is too high to simply follow expectantly. Cancer (Cancer Cytopathol) 2012. © 2011 American Cancer Society.
Multigrid solution of non‐linear balance equations in meteorology
Authors: Fulton Scott R.
Published: September 2011

Multigrid algorithms are presented for several elliptic problems arising in models of balanced atmospheric dynamics. The equations are generalizations of the Monge—Ampere equation and are non‐linear in the highest‐order terms. The problem formulation is reviewed, along with a method of dealing with a lower boundary which is not a co‐ordinate surface, and details of the discretization and relaxation are given. Numerical results from two‐ and three‐dimensional problems show the accuracy and efficiency of the method.