bluuebunny/crossref_metadata_2025 huggingface dataset:
Irreversible thermoinactivation of ribonuclease‐A by soft‐hydrothermal processing
Authors: Miyamoto Toru , Okano Shinya , Kasai Noriyuki
Published: September 2009

Ribonuclease (RNase), which often represents molecular biological contamination, is a thermostable enzyme. When RNase is heated at 121°C by autoclave sterilization for 20 min, it does not lose its activity. However, the nature of the molecular events by which the irreversible denaturation occurs remains unknown. The purpose of this study was to elucidate the molecular mechanisms of irreversible thermal denaturation of RNase A and to develop an advanced sterilization method using soft‐hydrothermal processing, which has the advantages of improved safety and cost‐efficiency. The enzymatic activity of RNase was measured using polyacrylamide gel electrophoresis with torula yeast RNA. We evaluated the temperature and time course of irreversible thermoinactivation of RNase by normal autoclaving, hot‐air sterilization, and soft‐hydrothermal processing that had been controlled to the desired steam saturation ratio. The results indicated that RNase A was deactivated by autoclave sterilization (121°C, 20 min) immediately after treatment, but was reactivated over time. Hot‐air sterilization (180°C, atmospheric pressure, 60 min) produced results similar to that of autoclave sterilization. In contrast, RNase A was irreversibly thermoinactivated by soft‐hydrothermal processing (110°C, 20 min) at 100% steam saturation ratio. We also determined that the mechanism of irreversible thermoinactivation of RNase A involved hydrolysis and deamidation under this condition at a steam saturation ratio of more than 100%. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Using highly efficient nonlinear experimental design methods for optimization of Lactococcus lactis fermentation in chemically defined media
Authors: Zhang Guiying , Block David E.
Published: September 2009

Optimization of fermentation media and processes is a difficult task due to the potential for high dimensionality and nonlinearity. Here we develop and evaluate variations on two novel and highly efficient methods for experimental fermentation optimization. The first approach is based on using a truncated genetic algorithm with a developing neural network model to choose the best experiments to run. The second approach uses information theory, along with Bayesian regularized neural network models, for experiment selection. To evaluate these methods experimentally, we used them to develop a new chemically defined medium for Lactococcus lactis IL1403, along with an optimal temperature and initial pH, to achieve maximum cell growth. The media consisted of 19 defined components or groups of components. The optimization results show that the maximum cell growth from the optimal process of each novel method is generally comparable to or higher than that achieved using a traditional statistical experimental design method, but these optima are reached in about half of the experiments (73–94 vs. 161, depending on the variants of methods). The optimal chemically defined media developed in this work are rich media that can support high cell density growth 3.5–4 times higher than the best reported synthetic medium and 72% higher than a commonly used complex medium (M17) at optimization scale. The best chemically defined medium found using the method was evaluated and compared with other defined or complex media at flask‐ and fermentor‐scales. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Results of a multicenter, randomized, double‐blind, dose‐evaluating phase 2/3 study of lenalidomide in the treatment of metastatic malignant melanoma
Authors: Glaspy John , Atkins Michael B. , Richards Jon M. , Agarwala Sanjiv S. , O'Day Steven , Knight Robert D. , Jungnelius J. Ulf , Bedikian Agop Y.
Published: September 2009

BACKGROUND:

There are currently no systemic treatments for stage IV melanoma, which have been proven in randomized trials to benefit overall survival (OS). Lenalidomide has efficacy against melanoma in animal models and safety in phase 1 trials. The authors reported the results of a phase 2/3 study comparing the safety and efficacy of 2 doses of lenalidomide in patients with relapsed metastatic melanoma disease refractory to previous treatment with dacarbazine, temozolomide, interleukin‐2, or interferon‐α.

METHODS:

A total of 294 patients were randomized to oral lenalidomide at 5 mg or 25 mg dose. Tumor response, time to progression, and OS were evaluated. Treatment continued until disease progression or unacceptable adverse events.

RESULTS:

No significant differences in response rate, OS, or time to progression were observed between lenalidomide 25 mg versus 5 mg (overall response rate: 5.5% vs 3.4%, P = .38; median OS: 6.8 months vs 7.2 months, P = .71; and median time to progression: 2.2 months vs 1.9 months, P = .24). Myelosuppression was observed in 37.0% of patients in the 25 mg group and 13.7% of patients in the 5 mg group. Treatment‐related serious adverse events were seen in 39.0% of patients at the 25 mg dose and 35.4% of patients at the 5 mg dose.

CONCLUSIONS:

Despite the occurrence of treatment‐related serious adverse events, ∼80% of patients continued treatment. The higher dose of lenalidomide did not improve response rate, time to progression, or OS of patients with relapsed/refractory stage IV melanoma. A parallel placebo‐controlled study has been conducted to further assess the efficacy of lenalidomide in stage IV melanoma patients. Cancer 2009. © 2009 American Cancer Society.
Estimation of Surface Structure and Carbon Monoxide Oxidation Site of Shape‐Controlled Pt Nanoparticles
Authors: Nakamura Masashi , Hanioka Yuto , Ouchida Wataru , Yamada Mami , Hoshi Nagahiro
Published: September 2009

Surface structures of shape‐controlled Pt nanoparticles have been estimated using cyclic voltammetry (CV) and infrared reflection absorption spectroscopy (IRAS). Cubic and cuboctahedral Pt nanoparticles are prepared using a capping polymer. These nanoparticles give CVs similar to those of single crystal electrodes of Pt in sulfuric acid solution. The CV of cubic nanoparticles is similar to that of the Pt(510) [=5(100)–(110)] electrode, while the CV of cuboctahedral nanoparticles is reproduced well with the convolution of Pt(766) [=13(111)–(100)] and Pt(17 1 1) [=9(100)–(111)] electrodes. These results suggest that the planes of the cubic and cuboctahedral nanoparticles are composed of step‐terrace and atomically flat terraces, respectively. Adsorbed carbon monoxide (CO) on the shape‐controlled nanoparticles gives the IR bands that are assigned to on‐top and bridged CO. The band of on‐top CO is deconvoluted to two bands: the higher and the lower frequency bands are assigned to the CO on the plane and the edges of the nanoparticles, respectively. On‐top CO adsorbed on the edges is oxidized at more negative potential than that on the planes. Edge sites of the nanoparticles promote CO oxidation.
Real‐time performance evaluation of asynchronous time division traffic‐aware and delay‐tolerant scheme inad hocsensor networks
Authors: Mavromoustakis Constandinos X. , Karatza Helen D.
Published: September 2009

Wireless infrastructureless networks demand high resource availability with respect to the progressively decreasing energy consumption. A variety of new applications with different service requirements demand fairness to the service provision and classification, and reliability in an end‐to‐end manner. High‐priority packets are delivered within a hard time delay bound whereas improper power management in wireless networks can substantially degrade the throughput and increase the overall energy consumed. In this work a new scheme is being proposed and evaluated in real time using a state‐based layered oriented architecture for energy conservation (EC). The proposed scheme uses the node's self‐tuning scheme, where each node is assigned with a dissimilar sleep and wake time, based on traffic that is destined for each node. This approach is based on stream's characteristics with respect to different caching behavioral and storage‐capacity characteristics, and considers a model concerning the layered connectivity characteristics for enabling the EC mechanism. EC characteristics are modeled and through the designed tiered architecture the estimated metrics of the scheme can be bounded and tuned into certain regulated values. The real‐time evaluation results were extracted by using dynamically moving and statically located sensor nodes. A performance comparison is done with respect to different data traffic priority classifications following a real‐time asymmetrical transmission channel. Results have shown the scheme's efficiency in conserving energy while the topology configuration changes with time. Copyright © 2009 John Wiley & Sons, Ltd.
“I'm not physically active ‐ I only go for walks”: Physical activity in patients with longstanding eating disorders
Authors: Bratland‐Sanda Solfrid , Sundgot‐Borgen Jorunn , Rø Øyvind , Rosenvinge Jan H , Hoffart Asle , Martinsen Egil W
Published: September 2009

Objective

To examine self reported versus objectively assessed moderate‐to‐vigorous physical activity (MVPA), and different reasons for exercise, in patients with longstanding eating disorders (ED) when compared with controls.

Method

Inpatient females (n = 59, mean 30.1 years) and nonclinical age matched controls (n = 53, mean 31.3 years) accepted participation in this cross sectional study. Instruments included accelerometer ActiGraph, physical activity diary, Reasons for Exercise Inventory, and Eating Disorders Examination interview.

Results

Self reported and objectively assessed MVPA were higher across all ED diagnoses when compared with controls. The patients' self reported MVPA was lower than the objectively assessed MVPA; no difference was found in controls. Regulation of negative affects, not weight/appearance, was a more important, whereas fitness/health was a less important reason for exercise in patients than controls.

Discussion

The underreporting of MVPA in some patients with ED may warrant clinical attention. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010; 43:88–92
The outermost N‐terminal region of tapasin facilitates folding of major histocompatibility complex class I
Authors: Roder Gustav , Geironson Linda , Darabi Anna , Harndahl Mikkel , Schafer‐Nielsen Claus , Skjødt Karsten , Buus Søren , Paulsson Kajsa
Published: September 2009

Tapasin (Tpn) is an ER chaperone that is uniquely dedicated to MHC‐I biosynthesis. It binds MHC‐I molecules, integrates them into peptide‐loading complexes, and exerts quality control of the bound peptides; only when an “optimal peptide” is bound will the MHC‐I be released and exported to the cell surface for presentation to T cells. The exact mechanisms of Tpn quality control and the criteria for being an optimal peptide are still unknown. Here, we have generated a recombinant fragment of human Tpn, Tpn1–87 (representing the 87 N‐terminal and ER‐luminal amino acids of the mature Tpn protein). Using a biochemical peptide–MHC‐I‐binding assay, recombinant Tpn1–87 was found to specifically facilitate peptide‐dependent folding of HLA‐A*0201. Furthermore, we used Tpn1–87 to generate a monoclonal antibody, αTpn1–87/80, specific for natural human Tpn and capable of cellular staining of ER localized Tpn. Using overlapping peptides, the epitope of αTpn1–87/80 was located to Tpn40–44, which maps to a surface‐exposed loop on the Tpn structure. Together, these results demonstrate that the N‐terminal region of Tpn can be recombinantly expressed and adopt a structure, which at least partially resembles that of WT Tpn, and that this region of Tpn features chaperone activity facilitating peptide binding of MHC‐I.
The cellular and biochemical rules of lipid antigen presentation
Authors: De Libero Gennaro , Collmann Anthony , Mori Lucia
Published: September 2009

The recognition of both protein and lipid antigens follows similar strategies that rely on different molecular mechanisms. APC present lipid antigens exploiting the same mechanisms implicated in lipid translocation, lipoprotein assembly and lipid degradation. An important issue is how the lipid structure contributes to antigenicity. Lipid hydrophobicity influences the modes of internalization by APC, the trafficking through different membrane compartments, the binding to CD1 molecules and the stability of antigenic complexes. Some glycolipids with large hydrophilic parts require processing of the sugar moieties exerted by lysosomal hydrolases. Finally, extraction of lipids from membranes, their solubilization and loading on CD1 molecules are facilitated by the same lysosomal lipid‐binding proteins that are also instrumental in lipid catabolism. More recent investigations reveal how lipid‐specific immunity is regulated during infections. In this review we describe the main cellular and biochemical rules of lipid antigen presentation and discuss their implications in anti‐microbial and autoimmune responses.
Polyoxometalates in Polyelectrolyte Multilayer Films: Direct Loading of [H7P8W48O184]33–vs. Diffusion into the Film
Authors: Ball Vincent , Bernsmann Falk , Werner Sandra , Voegel Jean‐Claude , Piedra‐Garza Luis Fernando , Kortz Ulrich
Published: September 2009

The immobilization of polyoxometalates (POMs) into thin organized films is of major importance for the development of functional devices like electrochromic films and catalysts. We investigate herein two methods to incorporate the wheel‐shaped tungstophosphate [H7P8W48O184]33–(P8W48) polyoxometalates (POM) into polyelectrolyte multilayer (PEM) films, which offer the advantage of controlled thickness and ease of processability. The first method, whose feasibility has been widely demonstrated, consists in the alternate deposition of a polycation and the negatively charged POM. The second method has never been used to load POMs into thin films: an exponentially grown polyelectrolyte multilayer film, made from sodium hyaluronate (HA) and poly‐L‐lysine (PLL), is brought in contact with the POM solution to allow its passive diffusion into the PEM film. Both methods of incorporation are compared in terms of effective POM concentration in the film. In addition it is shown that the second method leads to a maximum in the amount of incorporated POM as a function of its concentration in solution.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Synthetic Approaches to Novel Thiosugar Scaffolds Containing α,β‐Unsaturated Carbonyl Groups
Authors: Xavier Nuno M. , Madeira Paulo J. A. , Florêncio M. Helena , Rauter Amélia P.
Published: September 2009

The synthesis of new classes of highly functionalized thiosugar derivatives containing α,β‐unsaturated carbonyl functions has been accomplished through simple and efficient strategies. 5‐Thiosugar‐fused butenolides and a 5‐thiohex‐1‐enopyran‐3‐ulose were constructed from easily available starting 3‐uloses by practical and reliable approaches. The reaction sequence used for the bicyclic fused derivatives involved Wittig olefination of protected pento‐ or hexofuran‐3‐uloses, introduction of a sulfhydryl group at C‐5 of the intermediate unsaturated ester and acid‐promoted deprotection, which allowed intramolecular lactonization and conversion into the 5‐thiopyranose form. For the synthesis of a 5‐thiohex‐1‐enopyran‐3‐ulose, a sulfhydryl functionality was introduced at C‐5 on a masked 3‐ulose derived from 1,2:5,6‐di‐O‐isopropylidene‐α‐D‐ribo‐hexofuranos‐3‐ulose. Acidhydrolysis displaced the equilibrium towards the 5‐thiopentopyran‐3‐ulose, which on pyridine‐mediated acetylation underwent 1,2‐elimination of acetic acid to give the desired α,β‐unsaturated 5‐thiopyranulose. This straightforward pathway provided the target compound in 37 % overall yield. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Vinylic Substitutions Promoted by PhSeZnCl: Synthetic and Theoretical Investigations
Authors: Santoro Stefano , Battistelli Benedetta , Testaferri Lorenzo , Tiecco Marcello , Santi Claudio
Published: September 2009

Vinyl selenides can be easily obtained through nucleophilic substitution of the corresponding halides by using PhSeZnCl in THF as well as “on water” conditions. The reaction is stereospecific with retention of the alkene geometry. The only exception has been observed in the reaction conducted on a β‐chloro‐α,β‐unsaturated ketone, which afforded the (Z) product starting from either the (E) or (Z) isomer. DFT calculations have been performed in order to investigate the reaction mechanism, the stereochemistry of the process and the role of the zinc atom. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Enamine–Metal Lewis Acid Bifunctional Catalysis: Application to Direct Asymmetric Aldol Reaction of Ketones (Eur. J. Org. Chem. 27/2009)
Authors: Xu Zhenghu , Daka Philias , Budik Ilya , Wang Hong , Bai Fu‐Quan , Zhang Hong‐Xing
Published: September 2009

The cover picture shows aldol reactions catalyzed by an enamine–metal Lewis acid bifunctional catalyst. The proposed transition state is also shown at the top. This bifunctional catalyst was developed by using a tridentate ligand to bring the Lewis acid and Lewis base in close proximity without quenching each other. The catalyst was found to catalyze aldol reactions in high activity and stereoselectivity. Details are discussed in the Short Communication by H. Wong et al. on p. 4581 ff. The authors acknowledge Bo Wang for helping with the cover page design and Mike Novak for useful discussions.
Nanomaterials as electrochemical detectors in microfluidics and CE: Fundamentals, designs, and applications
Authors: Pumera Martin , Escarpa Alberto
Published: September 2009

The different approaches for constructing nanomaterial‐based detectors for conventional CE and microchip electrophoresis are described in this review. They include three main types of nanomaterials, including carbon nanotubes, nanoparticles, and nanorods in various designs. The fundamental reasons for the enhanced detection performance of nanomaterial‐based detectors, such as higher sensitivity, improved limits of detection, and higher peak capacity, are discussed in detail. Various applications for biomedical, food, and environmental analyses are reviewed.
Optimal reconfiguration and capacitor placement by robust searching hybrid differential evolution
Authors: Chang Chung‐Fu
Published: September 2009

This paper aims to study distribution system operations by the robust searching hybrid differential evolution (RSHDE) method. The objective of this study is to present new algorithms for solving the optimal feeder reconfiguration problem, the optimal capacitor placement problem, and the problem of a combination of the two. Mathematically, the problem of this research is a nonlinear programming problem with integer variables. This paper presents a new approach which employs the RSHDE algorithm with integer variables to solve the problem. Depending on the initial assignment of the integer variables, the HDE may fail to find the initial search direction for large‐scale integer system. This is because the HDE applies a random search at its initial stages. Therefore, two new schemes, the multi‐direction search scheme and the search space reduction scheme, are embedded into the HDE. These two schemes are used to enhance the search ability before performing the initialization step of the solution process. The proposed approach is demonstrated using an IEEE illustrative example and one practical distribution network of Taiwan Power Company (TPC). Moreover, the previous HDE, simulated annealing (SA) and genetic algorithms (GA) methods are also applied to the same example systems for the purpose of comparison. Copyright © 2009 John Wiley & Sons, Ltd.
Stability of single‐wavelength optical buffers
Authors: Rogiest W. , Morozov E. , Fiems D. , Laevens K. , Bruneel H.
Published: September 2009

Optical burst switching (OBS) provides a future‐proof alternative to the current electronic switching in the backbone, but has buffering implemented with a set of fiber delay lines (FDLs). The resulting buffering system fundamentally differs from a classic one, in that the set of possible waiting times is not a continuum (like in the classic case) but rather a denumerable set, each value corresponding to the length of a delay line. As a result, arriving bursts in general have to wait longer than they would in a classic buffer, since their waiting time has to be in that denumerable set. The additional delay results in overall longer waiting times, when compared to a classic infinite buffer system with a continuous waiting room.

While previous work already focused on the performance evaluation of finite optical buffers, the stability problem of the infinite system received only little attention. This contribution is the first to present a complete proof of sufficient stability conditions in the case of a general infinite FDL set, general arrival process and general service times. The key elements of analysis is the exploiting of the regenerative property of the waiting‐time process and a characterisation of the limiting forward renewal time process. The given bound on the traffic load guarantees stability for a wide class of GI/G/1 optical buffers, and poses no restriction on the FDL lengths. Copyright © 2009 John Wiley & Sons, Ltd.
Verification of a mixed high‐order accurate DNS code for laminar turbulent transition by the method of manufactured solutions
Authors: Silva H. G. , Souza L. F. , Medeiros M. A. F.
Published: September 2009

This paper presents results on a verification test of a Direct Numerical Simulation code of mixed high‐order of accuracy using the method of manufactured solutions (MMS). This test is based on the formulation of an analytical solution for the Navier–Stokes equations modified by the addition of a source term. The present numerical code was aimed at simulating the temporal evolution of instability waves in a plane Poiseuille flow. The governing equations were solved in a vorticity–velocity formulation for a two‐dimensional incompressible flow. The code employed two different numerical schemes. One used mixed high‐order compact and non‐compact finite‐differences from fourth‐order to sixth‐order of accuracy. The other scheme used spectral methods instead of finite‐difference methods for the streamwise direction, which was periodic. In the present test, particular attention was paid to the boundary conditions of the physical problem of interest. Indeed, the verification procedure using MMS can be more demanding than the often used comparison with Linear Stability Theory. That is particularly because in the latter test no attention is paid to the nonlinear terms. For the present verification test, it was possible to manufacture an analytical solution that reproduced some aspects of an instability wave in a nonlinear stage. Although the results of the verification by MMS for this mixed‐order numerical scheme had to be interpreted with care, the test was very useful as it gave confidence that the code was free of programming errors. Copyright © 2009 John Wiley & Sons, Ltd.
A fourth‐order finite‐difference method for solving the system of two‐dimensional Burgers' equations
Authors: Liao Wenyuan
Published: September 2009

A fourth‐order compact finite‐difference method is proposed in this paper to solve the system of two‐dimensional Burgers' equations. The new method is based on the two‐dimensional Hopf–Cole trans‐formation, which transforms the system of two‐dimensional Burgers' equations into a linear heat equation. The linear heat equation is then solved by an implicit fourth‐order compact finite‐difference scheme. A compact fourth‐order formula is also developed to approximate the boundary conditions of the heat equation, while the initial condition for the heat equation is approximated using Simpson's rule to maintain the overall fourth‐order accuracy. Numerical experiments have been conducted to demonstrate the efficiency and high‐order accuracy of this method. Copyright © 2009 John Wiley & Sons, Ltd.
Element‐free Galerkin method for thermosolutal convection and macrosegregation
Authors: Sajja Udaya K. , Felicelli Sergio D.
Published: September 2009

In the present work, the element‐free Galerkin (EFG) method is applied to a continuum solidification model that calculates thermosolutal convection and macrosegregation during dendritic solidification of multicomponent alloys. Simulations for directional solidification of a binary Pb–Sn alloy and a Ni‐base quaternary alloy have been performed in a rectangular two‐dimensional domain. In both calculations, the alloy melt is cooled from below and the growth of the mushy zone is followed in time. The formation of macrosegregation defects known as ‘freckles’ has been successfully simulated using the meshless EFG method. A varying degree of sensitivity of results to the number and distribution of meshfree particles was obtained. The potential of the method for a broader range of solidification models is discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Spreads versus professional forecasters as predictors of future output change
Authors: Aretz Kevin , Peel David A.
Published: September 2009

We examine whether real output forecasts obtained from the Survey of Professional Forecasters efficiently embody information in the term structure spread. To this end, we employ revised data as well as real‐time vintage data, and we also allow for the possible impact of asymmetric loss functions. Assuming quadratic loss, our results suggest that the term structure spread does contain information useful for forecasting not reflected in the survey forecasts, at least over the longest forecast horizon. However, if we allow agents' loss functions to become more negatively skewed with the forecast horizon, then we cannot reject the rationality of the survey forecasts. Copyright © 2009 John Wiley & Sons, Ltd.
Equity and efficiency in HIV‐treatment in South Africa: the contribution of mathematical programming to priority setting
Authors: Cleary Susan , Mooney Gavin , McIntyre Di
Published: September 2009

The HIV‐epidemic is one of the greatest public health crises to face South Africa. A health care response to the treatment needs of HIV‐positive people is a prime example of the desirability of an economic, rational approach to resource allocation in the face of scarcity. Despite this, almost no input based on economic analysis is currently used in national strategic planning.

While cost‐utility analysis is theoretically able to establish technical efficiency, in practice this is accomplished by comparing an intervention's ICER to a threshold level representing society's maximum willingness to pay to avoid death and improve health‐related quality of life. Such an approach has been criticised for a number of reasons, including that it is inconsistent with a fixed budget for health care and that equity is not taken into account. It is also impractical if no national policy on the threshold exists. As an alternative, this paper proposes a mathematical programming approach that is capable of highlighting technical efficiency, equity, the equity/efficiency trade‐off and the affordability of alternative HIV‐treatment interventions. Government could use this information to plan an HIV‐treatment strategy that best meets equity and efficiency objectives within budget constraints. Copyright © 2009 John Wiley & Sons, Ltd.
International creative tension study of university students in South Korea and Finland
Authors: Chang Yoon , Eklund Tomas , Kantola Jussi I. , Vanharanta Hannu
Published: September 2009

The goal of this research was to compare the creative tension of university students in South Korea and Finland at three different universities. The creative tension, or the gap between a personal vision and the current reality, was analyzed according to relevant competences in a project manager's work role. In this case, students acted as the project managers in their role of completing all the requirements of their degree. The application used for collecting and analyzing the data was Cycloid, a project manager's work role–based competence application and a model in the generic Evolute system supporting fuzzy logic applications. Data for 108 university students were collected online through self‐evaluations. The application was able to identify the creative tension in each group of university students, and the results show major differences in creative tension across the universities (and also between countries). This type of in‐depth analysis into the cultural perceptions of attributes offers valuable new information for academia and businesses in the assessment and improvement of multicultural understanding and cooperation in areas of mutual interest and business. © 2009 Wiley Periodicals, Inc.
Ursodeoxycholic acid switches oxaliplatin‐induced necrosis to apoptosis by inhibiting reactive oxygen species production and activating p53‐caspase 8 pathway in HepG2 hepatocellular carcinoma
Authors: Lim Sung‐Chul , Choi Jeong Eun , Kang Ho Sung , SI Han
Published: September 2009

Hepatocellular carcinoma (HCC) is resistant to chemotherapy. Recently, however, several oxaliplatin‐based combinatorial treatments have shown a promising anti‐tumor activity in patients with HCC. Presently, we demonstrate that oxaliplatin triggers necrosis more than apoptosis in HepG2, SK‐Hep1, SNU‐423 and Hep3B HCC cells, while mainly inducing apoptosis in HCT116 and HT29 colon cancer cells. Interestingly, ursodeoxycholic acid (UDCA), a less hydrophobic bile acid that can suppress carcinogenesis, shifted oxaliplatin‐induced necrosis to apoptosis in HepG2 cells. The same effect was produced by hydrophilic bile acids (tauroursodeoxycholic acid and taurohyodeoxycholic acid), but not by highly hydrophobic bile acids (deoxycholic acid and chenodeoxycholic acid). UDCA also triggered the necrosis‐to‐apoptosis switch when cotreated with other platinum‐based chemotherapeutic drugs including cisplatin and carboplatin, suggesting that the cell death mode switching effect of UDCA is a general phenomenon when combined with platinum drugs. Oxaliplatin produced high level of reactive oxygen species (ROS) in HepG2 cells and UDCA significantly reduced oxaliplatin‐induced ROS generation. In addition, N‐acetyl‐L‐cysteine and the superoxide scavengers butylated hydroxyanisole and dihydroxybenzene‐3,5‐disulfonic acid attenuated necrosis, indicating a critical role(s) of ROS in occurrence of necrotic death. Apoptosis induced by combined treatment appeared to be mediated by p53‐caspase 8‐caspase 3 pathway. In conclusion, UDCA switches oxaliplatin‐induced necrosis to apoptosis via inhibition of ROS production and activation of the p53‐caspase 8 pathway in HepG2 cells. As necrosis and subsequent inflammation are implicated in tumor progression and malignancy, our results imply a potential improved efficacy of UDCA‐combined chemotherapy in HCC by reducing inflammatory responses that may be triggered by oxaliplatin.
Lung cancer mortality trends in 36 European countries: secular trends and birth cohort patterns by sex and region 1970–2007
Authors: Bray Freddie Ian , Weiderpass Elisabete
Published: September 2009

Smoking is a major contributor to all‐cause mortality in Europe and accounts for one‐fifth of the cancer‐related deaths. Monitoring the tobacco epidemic via an analysis of lung cancer trends is essential in helping countries arrest the effects of tobacco epidemic in the region. The study aims to provide a comprehensive and up‐to‐date overview of the temporal patterns of lung cancer mortality in Europe, emphasizing country‐ and sex‐specific differences. National lung cancer mortality data were extracted from the WHO mortality databank by age, sex, year of death (1970–2007) for 36 countries in Europe. Trends in lung cancer mortality in men have tended to decrease in many European countries during the last two decades, particularly in North and Western Europe. Among women, mortality rates are still increasing in many countries, although in a few populations, rates are beginning to stabilize, notably in the high‐risk countries within Eastern Europe (Hungary, Poland and the Czech Republic), and in Northern Europe (Denmark, Iceland and the United Kingdom). Men and women are clearly in very different phases of the smoking epidemic, and, as reflected in the mortality rates by birth cohort, the stage varies widely by country within each European region. That lung cancer mortality trends in men are on a downwards path in most European countries while female rates continue to rise, points to an urgent need for national and European prevention strategies that target tobacco cessation and prevention among European women.
Business cycle synchronization of the euro area with the new and negotiating member countries
Authors: Savva Christos S. , Neanidis Kyriakos C. , Osborn Denise R.
Published: September 2009

We examine business cycle synchronizations between the euro area and the recently acceded EU and currently negotiating countries. Strong evidence is uncovered of time‐variation in the degree of co‐movement between the cyclical components of monthly industrial production indicators for each of these countries with a euro area aggregate, which is modelled through a bivariate VAR‐GARCH specification with a smoothly time‐varying correlation that allows for structural change. Where required to account for the observed time‐variation in correlations, a double smooth transition conditional correlation model is used to capture a second structural change event. After allowing for dynamics, we find that all new EU members and negotiating countries have at least doubled their business cycle synchronization with the euro area or changed from negative to positive correlations, since the early 1990s. Furthermore, some have exhibited U‐curved or hump‐shaped business cycle correlation patterns. The results point to great variety in timing and speed of the correlation shifts across the country sample. Copyright © 2009 John Wiley & Sons, Ltd.
Child temperament in three U.S. cultural groups
Authors: Bornstein Marc H. , Cote Linda R.
Published: September 2009

Temperament among children (N = 111 20‐month‐olds) from three cultural backgrounds in the United States (Latin American, Japanese American, and European American) was investigated. In accord with a biobehavioral universalist perspective on the expression of early temperament, few significant group differences in child temperament were found, regardless of cultural background; however, factors associated with maternal reports of child temperament differed by cultural group. The findings provide insight into the nature of child temperament generally and temperament of children in immigrant families specifically as well as parenting in immigrant families.
Predictors of coparenting in Mexican American families and links to parenting and child social emotional development
Authors: Cabrera Natasha J. , Shannon Jacqueline D. , La Taillade Jaslean J.
Published: September 2009

The present study examined associations between parents' levels of acculturation depressive symptoms, family support, and couple relationship quality with coparenting conflict. We also explored the effects of coparenting conflict on parenting and infant social development in a sample of low‐income Mexican American (n = 735) infants (age 9 months) and their parents. Results indicated that couple conflict was the strongest predictor of coparenting conflict. Coparenting conflict had a significant effect on mother‐‐infant interaction and father engagement. The effects of coparenting on father caregiving varied by father's level of acculturation; when there is high coparenting conflict, more acculturated fathers engaged in more caregiving than do less acculturated fathers. Coparenting conflict was not predictive of infant social development.
Leptin and insulin induce mutual resistance for nitric oxide synthase III activation in adipocytes
Authors: Mehebik‐Mojaat Nadia , Ribière Catherine , Niang Fatoumata , Forest Claude , Jaubert Anne‐Marie
Published: September 2009

Obesity‐induced hyperleptinemia is frequently associated with insulin resistance suggesting a crosstalk between leptin and insulin signaling pathways. Our aim was to determine whether insulin and leptin together interfere on NOS activation in adipocytes. We examined insulin and leptin‐induced nitric oxide synthase (NOS) activity, protein amount and NOS III phosphorylation at Ser1179 in isolated epididymal adipocytes from rat, in the presence or not of inhibitors of kinases implicated in insulin or leptin signaling pathways. Insulin or leptin induced NOS III phosphorylation at Ser1179 leading to increased NO production in rat adipocytes, in agreement with our previous observations. When insulin and leptin at a concentration found in obese rats (10 ng/ml) were combined, NOS activity was not increased, suggesting a negative crosstalk between insulin and leptin signaling mechanisms. Chemical inhibitors of kinases implicated in signaling pathways of insulin, such as PI‐3 kinase, or of leptin, such as JAK‐2, did not prevent this negative interaction. When leptin signaling was blocked by PKA inhibitors, insulin‐induced NOS activity and NOS III phosphorylation at Ser1179 was observed. In the presence of leptin and insulin, (i) IRS‐1 was phosphorylated on Ser307 and this effect was prevented by PKA inhibitors, (ii) JAK‐2 was dephosphorylated, an effect prevented by SHP‐1 inhibitor. A mutual resistance occurs with leptin and insulin. Leptin phosphorylates IRS‐1 to induce insulin resistance while insulin dephosphorylates JAK‐2 to favor leptin resistance. This interference between insulin and leptin signaling could play a crucial role in insulin‐ and leptin‐resistance correlated with obesity. J. Cell. Biochem. 108: 982–988, 2009. © 2009 Wiley‐Liss, Inc.
A novel approach for correlative light electron microscopy analysis
Authors: Vicidomini Giuseppe , Gagliani Maria C. , Cortese Katia , Krieger Jens , Buescher Peter , Bianchini Paolo , Boccacci Patrizia , Tacchetti Carlo , Diaspro Alberto
Published: September 2009

Correlative light and electron microscopy (CLEM) is a multimodal technique of increasing utilization in functional, biochemical, and molecular biology. CLEM attempts to combine multidimensional information from the complementary fluorescence light microscopy (FLM) and electron microscopy (EM) techniques to bridge the various resolution gaps. Within this approach the very same cell/structure/event observed at level can be analyzed as well by FLM and EM. Unfortunately, these studies turned out to be extremely time consuming and are not suitable for statistical relevant data. Here, we describe a new CLEM method based on a robust specimen preparation protocol, optimized for cryosections (Tokuyasu method) and on an innovative image processing toolbox for a novel type of multimodal analysis. Main advantages obtained using the proposed CLEM method are: (1) hundred times more cells/structures/events that can be correlated in each single microscopy session; (2) three‐dimensional correlation between FLM and EM, obtained by means of ribbons of serial cryosections and electron tomography microscopy (ETM); (3) high rate of success for each CLEM experiment, obtained implementing protection of samples from physical damage and from loss of fluorescence; (4) compatibility with the classical immunogold and immunofluorescence labeling techniques. This method has been successfully validated for the correlative analysis of Russel Bodies subcellular compartments. Microsc. Res. Tech., 2010. © 2009 Wiley‐Liss, Inc.
Synthesis and antifungal evaluation of hydroxy‐3‐phenyl‐2H‐1,3‐benzoxazine‐2,4(3H)‐diones and their thioanalogs
Authors: Skála Pavel , Macháček Miloš , Vejsová Marcela , Kubicová Lenka , Kuneš Jiří , Waisser Karel
Published: September 2009

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A series of substituted 5‐, 6‐, 7‐, and 8‐hydroxy‐3‐phenyl‐2H‐1,3‐benzoxazine‐2,4(3H)‐diones (5–8) was synthesized by cyclization of corresponding dihydroxy‐N‐phenylbenzamides (1–4) with methyl chloroformate. The starting compounds 1–4 were prepared by the reaction of the respective dihydroxybenzoic acid, aniline and phosphorus trichloride via microwave irradiation. Thionation of compounds 8a, 8b, 8c, 8d employing Lawesson's reagent was used to prepare 5‐hydroxy‐3‐phenyl‐4‐thioxo‐3,4‐dihydro‐2H‐1,3‐benzoxazin‐2‐ones (10a, 10b, 10c, 10d) and 5‐hydroxy‐3‐phenyl‐2H‐1,3‐benzoxazine‐2,4(3H)‐dithiones (11a, 11b, 11c, 11d). The position of sulfur in monothionated derivatives 9c and 10a, 10b, 10c, 10d was confirmed by 2D NMR methods. Attempts to prepare dithionated derivatives from the isomeric 6‐, 7‐ or 8‐hydroxy compounds 5–7 failed. All compounds were tested for their in vitro antifungal activity against eight test strains. Compounds 1–4 showed moderate activity and the cyclization to corresponding hydroxy‐3‐phenyl‐2H‐1,3‐benzoxazine‐2,4(3H)‐diones (5–8) resulted in a decrease in antifungal activity. No antifungal activity was observed in thionated compounds 9c and 10–11. J. Heterocyclic Chem., (2009).
Synthesis of [2,4‐bis(arylamino)thiazol‐5‐yl](1‐methyl‐1H‐benzimidazol‐2‐yl)methanones
Authors: Abbs Fen Reji T. F. , Rajasekharan Kallikat N.
Published: September 2009

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[2,4‐Bis(arylamino)thiazol‐5‐yl]‐(1‐methyl‐1H‐benzimidazol‐2‐yl)methanones, as the analogs of the cytotoxic marine alkaloid dendrodoine, are synthesized and characterized by elemental analysis, IR, NMR, and Mass spectral data. The thiourea derivatives provide four ring atoms for the thiazole ring construction and thus act as [CNCS] synthons. The remaining carbon of the thiazole is sourced from 2‐(2‐bromoacetyl)‐1‐methyl‐1H‐benzimidazole. This [4+1] heterocyclization reaction is adopted for the synthesis of novel 1‐methyl‐1H‐benzimidazole derivatives. J. Heterocyclic Chem., (2009).
An efficient and convenient multicomponent reaction for the synthesis of 2‐methyl‐4,6‐diarylpyrimidine under solvent‐free conditions
Authors: Rong Liangce , Han Hongxia , Jiang Hong , Dai Yisi , Zhuang Mengjie , Cao Minxiang , Tu Shujiang
Published: September 2009

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An efficient and convenient method for the preparation of 2‐methyl‐4,6‐diarylpyrimidine derivatives by the multicomponent reactions of aromatic aldehydes, aromatic ketones, and acetamidine hydrochloride in the presence of sodium hydroxide under solvent‐free conditions was reported. This method has the advantages of excellent yields, mild reaction conditions, easy workup, and environmentally friendly procedure. J. Heterocyclic Chem., (2009).
Near‐infrared bis(indolium heptamethine cyanine) dyes with a spacer derived from oligo(ethylene glycol)
Authors: Wolinska Ewa , Henary Maged , Paliakov Ekaterina , Strekowski Lucjan
Published: September 2009

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Synthesis of a series of near‐infrared dimeric dyes is presented. The intramolecular dimers contain two chromophores linked with a conformationally flexible ether or oligoether bridge. Optical properties of the dyes are discussed. J. Heterocyclic Chem., (2009).
Synthesis of halogenoindirubins
Authors: Tanoue Yasuhiro , Ikoma Yousuke , Kai Norihisa , Nagai Takeshi
Published: September 2009

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The synthesis of halogenoindirubins was attempted. The reaction of 3‐acetoxy‐6‐bromoindole (5) with 6‐bromoisation (10) in methanol with Na2CO3 produced 6‐bromo‐6′‐fluoroindirubin (11) in 80% yield. Its structure determination was mainly undertaken using 1H NMR spectroscopy. A similar reaction gave 6′‐bromoindirubin (12) and 6‐bromoindirubin (3) in moderate yields. J. Heterocyclic Chem., (2009).
A simple, efficient, one‐pot three‐component domino synthesis of Hantzsch pyridines under solvent‐free condition
Authors: Nasr‐Esfahani Masoud , Karami Bahador , Behzadi Masoume
Published: September 2009

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In this article, efficient and simple preparation of Hantzsch pyridine derivatives by reaction of various aldehydes and β‐dicarbonyls in the presence of ammonium chlorate under solvent‐free condition at 80°C is reported. The advantages of this system are the one‐step procedure, high yields of the products, and the ability to carry out large‐scale reactions. J. Heterocyclic Chem., (2009).
Managed care physician organizations: Next generation of healthcare reform
Authors: Harri Stephen F.
Published: September 2009

This article focuses on the evolution of physician‐sponsored organizations in the managed care continuum. Given the amount of influence that physicians have on the overall level of healthcare expenditures within the U.S. economy, physician commitment to the managed care process is critical to truly drive the next round of managed care initiatives. The capital markets have recognized this and have contributed significant amounts of capital to fuel the development of for‐profit models called physician practice management companies.
The role of placental examination and its pathology in obstetric risk management
Authors: Lavery J. Patrick
Published: September 2009

The placenta is a marker of biologic events that occur during pregnancy. Placental pathologic examination gives insight to pregnancy‐related insults, which affect the newborn at and after birth. Clinicians and risk managers can use this information to identify the cause of newborn complications in cases suggested to be birth‐related injuries.
The impact of inefficient clinical diagnosis on the cost of managing low back pain
Authors: Gracovetsky Serge A. , Marriott Anne , Richards Mark P. , Newman Nicholas M. , Asselin Steeve
Published: September 2009

The clinical examination remains the pivotal factor in evaluating low back pain (LBP) for decisions concerning compensation and rehabilitation. Many practitioners believe it to be highly reliable, even though existing literature does not support this belief. Not only are there no data supporting the efficacy of clinical diagnosis for LBP, but also published data underscore its many inherent weaknesses. Healthcare risk managers need accurate clinical information to make decisions. If current clinical information is unreliable, then healthcare risk management strategies for LBP must be revised.
Planning for a bomb threat
Authors: Rozovsky Lorne E.
Published: September 2009

A bomb threat must always be taken seriously. It is important to have specific response plans in place, especially in a healthcare facility, where patients may be particularly vulnerable both to danger and to the threat of danger. Also, the facility may be judged in the community by how it responds to a threat. A prudent risk manager will plan in advance, setting up a chain of command and specific procedures, and familiarizing all who take on bomb threat duties not only with their responsibilities, but also with one another. There should be a familiar and easy relationship among those required to work together in stressful situations.
Pharmaceutical risk management: Special problems encountered in the hospital setting
Authors: Benjamin David M.
Published: September 2009

This article (1) reviews the types of adverse drug reactions that can occur, (2) discusses liability issues for hospitals and healthcare professionals who practice in a hospital or nursing home setting, and (3) presents risk management strategies for maximizing the quality of pharmaceutical care while minimizing exposure to risk.
The medicolegal risks of thermal injury during laparoscopic monopolar electrosurgery
Authors: Perantinides Paul G. , Tsarouhas Antonios P. , Katzman Van S.
Published: September 2009

Medicolegal liability claims arising from minimally invasive surgeries are rapidly increasing. While the medical community appears aware of certain types of liability risks in this area, it often underappreciates the risks associated with monopolar laparoscopic electrosurgery. Jury verdicts and settlements help define this problem, which can lead to improved healthcare delivery and better outcomes for patients.
Practical risk management principles for physicians
Authors: Bunting Robert F. , Benton Joyce , Morgan W. Donald
Published: September 2009

Most medical schools and postgraduate residency programs do not focus adequate attention on risk management and quality management issues. This article will prepare physicians with an adequate working knowledge of risk management and quality management information, which will enable them to practice more effectively in today's litigious and regulatory climate.