bluuebunny/crossref_metadata_2025 huggingface dataset:
A Highly Practical and Reliable Nickel Catalyst for Suzuki–Miyaura Coupling of Aryl Halides
Authors: Zhao Yu‐Long , Li You , Li Shui‐Ming , Zhou Yi‐Guo , Sun Feng‐Yi , Gao Lian‐Xun , Han Fu‐She
Published: June 2011

We disclose that [1,3‐bis(diphenylphosphino)methane]nickel(II) chloride [NiCl2(dppp)] is a highly active, universally applicable, cheap, and stable catalyst for Suzuki–Miyaura cross‐coupling reactions of aryl halides with a catalyst loading of lower than 1 mol%, and more notably, in the absence of extra supporting ligands. Under the optimized reaction conditions, a broad range of aryl bromides as well as the notoriously unreactive aryl chlorides, including activated, non‐activated, deactivated, and heteroaromatic and sterically hindered substrates can be coupled smoothly with various boronic acids (47 examples, 48–98% yields). In addition, the transformation is tolerant of various functional groups such as ether, ester, ketone, aldehyde, cyano, and unprotected amino and hydroxy groups. Finally, the potential utilization of the methodology was further demonstrated by the gram‐scale synthesis of several core structures of commercialized antihypertensive drugs and fungicides. Thus, the combination of high activity, broad applicability, cheapness, and high stability of NiCl2(dppp) presented in this work constitutes one of the few prominent catalysts which allow for practical and reliable construction of biaryls and heterobiaryls with structural diversity from readily available aryl halides and boronic acids.
Specters and Images: When the Levees Broke – A Requiem in Four Acts
Authors: Parasher Prajna
Published: June 2011

Spike Lee's When the Levees Broke: A Requiem in Four Acts (2006) is examined as a witnessing on the national scale of the trauma felt by those who experienced flooding in the aftermath of Katrina. The premise is that national acknowledgment of the wound, and this mourning, can only happen as the silence following trauma is drawn into public discourse. Spike Lee does this with a variety of interlocking filmic techniques including archival footage, interviews, vistas of devastation and commentary through music. Copyright © 2011 John Wiley & Sons, Ltd.
Bollywood as Witness: Changing Perceptions of Mental Illness in India (1913–2010)
Authors: Malik Mansoor , Trimzi Imran , Galluci Gerard
Published: June 2011

Indian cinema, affectionately known as Bollywood, makes more movies than Hollywood and is hugely influential in shaping social attitudes in the Indian subcontinent and many other parts of the world. In order to study depiction of mental illness, we searched anthology of Indian movies from 1930s up to the present. We divided this period into four arbitrary sections based on the broader political and socio‐economic climate in India. Movie plots were analyzed and information about the attitudes towards mental illness, accuracy and depiction of mental illness and the treatment methods portrayed was extracted. The key findings of the study were that attitudes towards mental illness in Indian cinema paralleled the broader political and socio‐economic trends in Indian society. In the age of political idealism, mental illness was portrayed as benign and amusing. With increasing political corruption and instability, mentally ill characters were depicted as cruel, deviant and psychopathic. The portrayal of mental illness is often inaccurate and exaggerated, keeping in line with the hyperbolic nature of Indian cinema. With increasing political and economic stabilization, attitudes are changing once again. Recent movies display more sympathy and understanding towards characters with mental illness. Copyright © 2011 John Wiley & Sons, Ltd.
Judgmental extrapolation and market overreaction: On the use and disuse of news
Authors: Andreassen Paul B.
Published: June 2011

The tendency of future stock prices to revert toward the mean of past prices was originally explained by the market overreaction hypothesis, which assumed that recent media reports cause investors to underuse base rate information. However, assuming that investors underweigh older stores of financial information cannot readily explain why mean reversion occurs primarily in January among former losers. An alternative psychological model based on intuitive time‐series extrapolation is presented. Investors' forecasts are held to vary as a function of the relative salience of, first, the recent versus the older levels of the price series, and second, the trend component of the price series. News reports, as normally provided by the media, are assumed to affect investors' forecasts by increasing the salience of any trend. Results of two market simulation experiments provided support for this assumption. Ways in which salience effects might account for the anomalies of the mean reversion phenomena are discussed.
Fermentation medium for collagenase production by Penicillium aurantiogriseum URM4622
Authors: Lima Carolina A. , Viana Marques Daniela A. , Neto Benício Barros , Lima Filho José L. , Carneiro‐da‐Cunha Maria G. , Porto Ana L. F.
Published: June 2011

Medium composition and culture conditions for maximal collagenase production by Penicillium aurantiogriseum URM4622 were optimized using a response surface approach. A full two‐level design on three factors (initial medium pH, soybean flour concentration, and temperature) was employed to identify the most significant fermentation parameters for collagenase production, and a subsequent central composite design (CCD) was used to find the optimal levels of the two most significant factors (initial medium pH and soybean flour concentration). The design results indicated that the initial medium pH and the temperature had significant negative main effects, whereas the substrate concentration had a positive effect on the collagenase production. The maximum collagenolytic activity predicted by the fitted response surface was expected to occur at pH 7.21, 1.645% soybean flour concentration and 24°C. Three replicate experiments were run at these conditions and yielded an activity response of 283.36 ± 1.33 U, which not only is the highest obtained in this study but also represents a 5‐fold increase over the lowest response observed in the initial design. Since all experiments were carried out with an inexpensive substrate, the final results point out to a cost‐effective medium for collagenase production with potential industrial‐scale applications. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Immobilized purple bacteria for light‐driven H2 production from starch and potato fermentation effluents
Authors: Tekucheva Darya N. , Laurinavichene Tatyana V. , Seibert Michael , Tsygankov Anatoly A.
Published: June 2011

The goal of the study was to show that immobilized purple bacteria could photoproduce H2 using dark fermentation effluent (FE) as substrate. Simple pretreatment of an inexpensive glass–fiber matrix accelerated the immobilization process. Photobioreactors (PhBR) containing immobilized Rhodobacter sphaeroides GL produced 0.128 L H2 h−1 L−1 of PhBR volume (0.570 L h−1 L−1 of matrix) for up to 3 months when continuously fed artificial media with volatile fatty acids (VFAs) or FE from potato and starch fermentations. Hydrogen production was insensitive to NH4+ up to 1 mM and saturated at 8 mM lactate or 1.5% potato FE (diluted in water and supplemented with critical micronutrients). The efficiency of VFA transformation to H2 was 50–70% of theoretical. At nonlimiting substrate concentrations in artificial media or FE, acetate was utilized before butyrate. High volumetric rates of continuous H2 photoproduction and stability of the process are advantages of using immobilized cultures. Use of H2 photoproduction as a polishing step in the treatment of FEs from dark fermentations increased the total amount of H2 produced from 0.9 to 4.7 mol mol−1 glucose equivalent in the original potato homogenate. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Conspicuous consumption orientation: Conceptualisation, scale development and validation
Authors: Roy Chaudhuri Himadri , Mazumdar S. , Ghoshal A.
Published: June 2011

In this paper individual differences in conspicuous tendencies are examined. A new definition of the construct is proposed and, through critical evaluation of the extant literature, the need for a proper scale is posited. Then an extensive exercise is taken up to develop and validate the scale. The 11‐item scale is found to be uni‐dimensional, to have a factor structure that is generalisable across student and non‐student samples, and has acceptable internal and test–retest reliabilities. The scale's validity is attested to by its theoretically tenable relationships with other personality measures. Copyright © 2011 John Wiley & Sons, Ltd.
Prior chemoradiotherapy adversely impacts outcomes of recurrent and second primary head and neck cancer treated with concurrent chemotherapy and reirradiation
Authors: Choe Kevin S. , Haraf Daniel J. , Solanki Abhishek , Cohen Ezra E. W. , Seiwert Tanguy Y. , Stenson Kerstin M. , Blair Elizabeth A. , Portugal Louis , Villaflor Victoria M. , Witt Mary Ellyn , Vokes Everett E. , Salama Joseph K.
Published: June 2011

BACKGROUND:

It has been shown that concomitant chemotherapy (C) with reirradiation (ReRT) is feasible and effective for select patients with recurrent or second primary head and neck cancer (HNC). To examine potential prognostic factors associated with survival, the authors of this report retrospectively reviewed the outcomes of patients who received CReRT.

METHODS:

The study cohort comprised previously irradiated patients with nonmetastatic disease from 9 consecutive phase 1 and 2 protocols for poor‐prognosis HNC. For all patients, reirradiation (ReRT) was delivered with concurrent chemotherapy. Chemotherapy generally was 5‐fluorouracil, hydroxyurea, and a third agent.

RESULTS:

One hundred sixty‐six patients were identified, including 81 patients who underwent surgical resection or debulking before enrollment. The median ReRT dose was 66 gray. After a median follow‐up of 53 months among surviving patients, the median overall survival (OS) was 10.3 months. The 2‐year rates for OS, disease‐free survival, locoregional control, and freedom from distant metastasis were 24.8%, 19.9%, 50.7%, and 61.4%, respectively. Thirty‐three patients (19.9%) died of treatment‐related toxicity. In subgroup analysis, survival was significantly reduced in patients who received previous concurrent chemoradiotherapy (CRT) compared with patients who were naive to CRT (2‐year OS rate, 10.8% vs 28.4%; P = .0043). In multivariable analysis, prior CRT was associated independently with OS along with surgery before protocol treatment, full‐dose ReRT, and radiotherapy interval.

CONCLUSIONS:

CReRT achieved a long‐term cure for a small group of patients with recurrent or second primary HNC. Previous treatment with CRT was among the important prognostic factors for survival. Because of the associated risk of severe toxicity, CReRT should be limited only to carefully selected patients. Cancer 2011;. © 2011 American Cancer Society.
Visual system scaling in teleost fish
Authors: Bakken Trygve E. , Stevens Charles F.
Published: June 2011

Teleost fish grow continuously throughout their lifespan, and this growth includes visual system components: eyes, optic nerves, and brain. As fish grow, the optic nerve lengthens and neural signals must travel increasing distances from the eye to the optic tectum along thousands of retinal ganglion cell (RGC) axons. Larger fish have better vision that enhances their ability to capture prey, but they are faced with the potential computational problem of changes in the relative timing of visual information arriving at the brain. Optic nerve conduction delays depend on RGC axon conduction velocities, and velocity is primarily determined by axon diameters. If axon diameters do not increase in proportion to body length, then absolute and relative conduction delays will vary with fish size. We have measured optic nerve lengths and axon diameter distributions in different sized zebrafish (Danio rerio) and goldfish (Carassius auratus) and find that, as both species of fish grow, axon diameters increase to reduce average conduction delays by about half and to keep relative delays constant. This invariance of relative conduction delays simplifies computational problems faced by the optic tectum. J. Comp. Neurol., 2012. © 2011 Wiley Periodicals, Inc.
SMEs and environmental responsibility: do actions reflect attitudes?
Authors: Cassells Sue , Lewis Kate
Published: June 2011

Globally there is mounting pressure for firms to assess their impact on the environment, and to modify their behaviour accordingly. The small and medium enterprise (SME) sector is often described as ‘hard to reach’ and lagging behind in terms of ‘green business’ due to management and resourcing issues characteristic of SMEs (e.g. resource poverty and a lack of management capability). This absence of resource slack then translates into an unwillingness and/or inability to commit to environmental improvements in any systematic and ongoing fashion, if at all. However, a lack of action in the context of the firm does not always reflect the personal attitudes of the individual SME owner‐managers. The link between attitude and action is explored in the paper through the examination of the inter‐relationship between awareness of environmental impact, attitude towards environmental issues, and environmental practice adoption. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment.
Relating sustainability theory to practice at Auckland airport: An engaged scholarship endeavour involving students
Authors: Kearins Kate , Fryer Martin
Published: June 2011

This paper results from an engaged scholarship endeavour involving an academic, a practitioner, and students. It describes salient interactions which sought to inform Auckland Airport's sustainability planning efforts, and which also provided research and learning opportunities. The company wanted to develop a comprehensive approach to sustainability following best practice. However, the practical reality was that staff were working under the mandate that the formal introduction of sustainability into the business needed to add value. Novel ideas were somewhat difficult to generate when the company was already deemed to be doing well; external stakeholders were not so willing to engage; sustainability performance reporting did not always find a ready audience; and external awareness of the company's sustainability initiatives was relatively low. These challenges to the business case offered excellent opportunities for student engagement. They also provided a test as to how theoretical ideals embracing broader systems thinking relate to on‐the‐ground practice. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment.
An exploratory study of sustainability as a stimulus for corporate entrepreneurship
Authors: Morrish Sussie C. , Miles Morgan P. , Polonsky Michael Jay
Published: June 2011

This paper examines sustainability as an emerging stimulus for corporate entrepreneurship in New Zealand publicly traded firms, using a process approach to sustainable corporate entrepreneurship. We find that many of the firms do not identify sustainability in their mission statement or in relationship to any product, process, strategy, or business model innovative initiative. Of those that do, there are varying degrees of inclusion and as such, sustainability does not seem to be widely or strategically considered a stimulus for corporate entrepreneurship by publicly held New‐Zealand‐based corporations. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment.
Integral responsibilities for a responsive and sustainable practice in organization and management
Authors: Küpers Wendelin M.
Published: June 2011

Based on an extended phenomenological understanding, this paper discusses the potential of a responsive, responsible and hence sustainable orientation integral to practice. First, basic ideas about a phenomenology of responsiveness are outlined, and then the notion of responsibility is discussed critically, opening it up towards an extended understanding. Based on an integral framework, different fields of application of responsibility for organization and its interrelation are presented. Finally, implications and perspectives for further investigating and incorporating responsive and integral responsibility for a sustainable organization are outlined. Copyright © 2011 John Wiley & Sons, Ltd and ERP Environment.
An algorithm for the computation of multiple Hopf bifurcation points based on Pade approximants
Authors: Girault G. , Guevel Y. , Cadou J.M.
Published: June 2011

Recently, a numerical method was proposed to compute a Hopf bifurcation point in fluid mechanics. This numerical method associates a bifurcation indicator and a Newton method. The former gives initial guesses to the iterative method. These initial values are the minima of the bifurcation indicator. However, sometimes, these minima do not lead to the convergence of the Newton method. Moreover, as only a single initial guess is obtained for each computation of the indicator, the computational time to obtain a Hopf bifurcation point can be quite long. The present algorithm is an enhancement of the previous one. It consists in automatically computing several initial guesses for each indicator curve. The majority of these initial values leads to the convergence of the Newton method. This method is evaluated through the problem of the lid‐driven cavity with several aspect ratios in the framework of the finite element analysis of the 2D Navier–Stokes equations. The results prove the efficiency and the robustness of the proposed algorithm. Copyright © 2011 John Wiley & Sons, Ltd.
Die Prothesen der Zukunft
Authors: Lenarz Thomas
Published: June 2011

Abbaubare Knochenschrauben, individualisierter Gelenkersatz, nervenzellfreundliche Hörimplantate: Dank neuer Fertigungstechniken und bioaktiver Materialien lässt sich nicht nur die Haltbarkeit, sondern auch die Funktion verschiedenster Prothesen gezielt verändern – und immer besser an den Organismus anpassen.
Fingolimod: new oral treatment for multiple sclerosis
Authors: Rog David
Published: June 2011

Fingolimod, a sphingosine‐1‐phosphate receptor modulator, is a novel oral treatment for multiple sclerosis. In this Drug profile the author reviews its mode of action, likely positioning and the advantages that it might offer in terms of clinical management of multiple sclerosis, and begins by setting the treatment context.
CCS – between a rock and a hard place?
Authors: Chadwick Andrew
Published: June 2011

For the past decade and a half, CO2 has been stored underground successfully, and scientists are becoming increasingly confident that carbon dioxide capture and storage (CCS) can work at the required scale. But many people are still not convinced about its viability and are worried about costs. Andrew Chadwick, Consultant Editor, considers what needs to be done to reassure the public and the investment community
The origins of glioma: E Pluribus Unum?
Authors: Siebzehnrubl F. A. , Reynolds B. A. , Vescovi A. , Steindler D. A. , Deleyrolle L. P.
Published: June 2011

Malignant glioma is among of the most devastating, and least curable, types of cancer. Since the re‐emergence of the cancer stem cell hypothesis, much progress has been made towards elucidating the cellular origin of these tumors. The hypothesis that tumors are hierarchically organized, with a cancer stem cell at the top that shares defining features with somatic stem cells and provides therapeutic refractoriness properties, has put adult stem cells into the limelight as prime suspect for malignant glioma. Much confusion still exists, though, as to the particular cell type and processes that lead to oncogenic transformation. In this review, we will discuss recent developments and novel hypotheses regarding the origin of malignant gliomas, especially glioblastoma. In particular, we argue that glioblastoma is the result of different pathways originating in multiple sources that all ultimately converge in the same disease. Further attention is devoted to potential scenarios leading to transformation of different stem/progenitor cell types of the brain, and the probability and relevance of these scenarios for malignant tumorigenesis. © 2011 Wiley‐Liss, Inc.
Evaluation of a virtual reality‐based memory training programme for Hong Kong Chinese older adults with questionable dementia: a pilot study
Authors: Man David W. K. , Chung Jenny C. C. , Lee Grace Y. Y.
Published: June 2011

Background

Older adults with questionable dementia are at risk of progressing to dementia, and early intervention is considered important. The present study investigated the effectiveness of a virtual reality (VR)‐based memory training for older adults with questionable dementia.

Methods

A pre‐test and post‐test design was adopted. Twenty and 24 older adults with questionable dementia were randomly assigned to a VR‐based and a therapist‐led memory training group, respectively. Primary outcome measures included the Multifactorial Memory Questionnaire and Fuld Object Memory Evaluation.

Results

Both groups demonstrated positive training effects, with the VR group showing greater improvement in objective memory performance and the non‐VR group showing better subjective memory subtest results in the Multifactorial Memory Questionnaire.

Conclusion

The use of VR seems to be acceptable for older adults with questionable dementia. Further study on the effect of educational background and memory training modality (visual, auditory) is warranted. Copyright © 2011 John Wiley & Sons, Ltd.
Translating visions of transparency and quality development: the transformation of clinical databases in the Danish hospital field
Authors: Kousgaard Marius Brostrøm
Published: June 2011

One of the most significant developments in the quest for quality, transparency, and accountability in healthcare is the construction and the implementation of indicator‐based technologies. In Denmark, this development has been relatively pronounced, and based on an extensive document study supplemented by qualitative interviews, this paper articulates a policy history of the clinical databases for quality from the early 1990s to the present. First, the paper outlines how, in the early 1990s, the National Board of Health and representatives from the medical profession place the clinical databases on the quality agenda in healthcare. Second, the paper shows that, in spite of an initial alignment between governmental and professional interests, the establishment of national clinical databases for quality turns out to be a difficult enterprise. Third, the paper elaborates how the public authorities respond to the challenges by re‐designing the governance framework for the databases. The transformations are characterized by increased centralization, standardization, specialization and regulative pressure. Finally, it is pointed out that although the course of events does constitute an increased institutionalization of the clinical databases, large variations exist and several databases have not yet realized the ambitions of transparency and quality improvement. Copyright © 2011 John Wiley & Sons, Ltd.
Exploring effects of rainfall intensity and duration on soil erosion at the catchment scale using openLISEM: Prado catchment, SE Spain
Authors: Baartman Jantiene E.M. , Jetten Victor G. , Ritsema Coen J. , de Vente Joris
Published: June 2011

In semi‐arid areas, high‐intensity rainfall events are often held responsible for the main part of soil erosion. Long‐term landscape evolution models usually use average annual rainfall as input, making the evaluation of single events impossible. Event‐based soil erosion models are better suited for this purpose but cannot be used to simulate longer timescales and are usually applied to plots or small catchments. In this study, the openLISEM event‐based erosion model was applied to the medium‐sized (∼50 km2) Prado catchment in SE Spain. Our aim was to (i) test the model's performance for medium‐sized catchments, (ii) test the ability to simulate four selected typical Mediterranean rainfall events of different magnitude and (iii) explore the relative contribution of these different storms to soil erosion using scenarios of future climate variability.

Results show that because of large differences in the hydrologic response between storms of different magnitudes, each event needed to be calibrated separately. The relation between rainfall event characteristics and the calibration factors might help in determining optimal calibration values if event characteristics are known. Calibration of the model features some drawbacks for large catchments due to spatial variability in Ksat values. Scenario calculations show that although ∼50% of soil erosion occurs as a result of high frequency, low‐intensity rainfall events, large‐magnitude, low‐frequency events potentially contribute significantly to total soil erosion. The results illustrate the need to incorporate temporal variability in rainfall magnitude–frequency distributions in landscape evolution models. Copyright © 2011 John Wiley & Sons, Ltd.
Oxygen binding to Arabidopsis thaliana AHb2 nonsymbiotic hemoglobin: evidence for a role in oxygen transport
Authors: Spyrakis Francesca , Bruno Stefano , Bidon‐Chanal Axel , Luque Francisco Javier , Abbruzzetti Stefania , Viappiani Cristiano , Dominici Paola , Mozzarelli Andrea
Published: June 2011

Nonsymbiotic hemoglobins AHb1 and AHb2 discovered in Arabidopsis thaliana are likely to carry out distinct physiological roles, in consideration of their differences in sequence, structure, expression pattern, and tissue localization. Despite a relatively fast autoxidation in the presence of O2, we were able to collect O2‐binding curves for AHb2 in the presence of a reduction enzymatic system. AHb2 binds O2 noncooperatively with a p50 of 0.021 ± 0.003 Torr, a value consistent with a recently proposed role in O2 transport. The analysis of the internal cavities derived from the structures sampled in molecular dynamics simulations confirms strong differences with AHb1, proposed to work as a NO deoxygenase in vivo. Overall, our results are consistent with a role for AHb2 as an oxygen carrier, as recently proposed on the basis of experiments on AHb2‐overexpressing mutants of A. thaliana. © 2011 IUBMB IUBMB Life, 63(5): 363–362, 2011.
The carbon monoxide‐releasing molecule, corm‐3 (ru(co)3cl(glycinate)), targets respiration and oxidases in campylobacter jejuni, generating hydrogen peroxide
Authors: Smith Holly , Mann Brian E. , Motterlini Roberto , Poole Robert K.
Published: June 2011

Carbon monoxide (CO) is a classical respiratory inhibitor, but CO‐releasing molecules (CO‐RMs) have therapeutic value, increasing phagocytosis, and reducing sepsis‐induced lethality. CORM‐3, Ru(CO)3Cl(glycinate), a ruthenium‐based carbonyl that liberates CO under physiological conditions, has previously been shown to inhibit bacterial growth and respiration, even at high concentrations of oxygen. Here, we report the effects of CORM‐3 on the microaerophilic foodborne pathogen Campylobacter jejuni. Even at CO‐RM (i.e., CO) concentrations that exceed dissolved oxygen levels, CORM‐3 does not inhibit microaerobic growth. This insensitivity is not due to failure of CORM‐3 to penetrate cells, as revealed by assay with extracellular myoglobin and by the ability of CO from externally added CORM‐3 to bind intracellular membrane‐associated respiratory oxidases. Even at almost 200 μ M oxygen, CORM‐3 inhibits formate‐dependent respiration and leads to generation of hydrogen peroxide. This work shows that CO‐RMs have valuable properties as antimicrobial agents; however, growth inhibition does not always accompany inhibition of respiration, even when ambient oxygen concentrations are low. © 2011 IUBMB IUBMB Life, 63(5): 363‐371, 2011
Structural heterogeneity and ligand gating in ferric methanosarcina acetivorans protoglobin mutants
Authors: Pesce Alessandra , Tilleman Lesley , Dewilde Sylvia , Ascenzi Paolo , Coletta Massimo , Ciaccio Chiara , Bruno Stefano , Moens Luc , Bolognesi Martino , Nardini Marco
Published: June 2011

Protoglobin from Methanosarcina acetivorans C2A (MaPgb), a strictly anaerobic methanogenic Archaea, displays peculiar structural and functional properties within members of the hemoglobin superfamily. In fact, MaPgb‐specific loops and a N‐terminal extension (20 amino acid residues) completely bury the heme within the protein matrix. Therefore, the access of diatomic gaseous molecules to the heme is granted by two apolar tunnels reaching the heme distal site from locations at the B/G and B/E helix interfaces. The presence of two tunnels within the protein matrix could be partly responsible for the slightly biphasic ligand binding behavior. Unusually, MaPgb oxygenation is favored with respect to carbonylation. Here, the crucial role of Tyr(B10)61 and Ile(G11)149 residues, located in the heme distal site and lining the protein matrix tunnels 1 and 2, respectively, on ligand binding to the heme‐Fe‐atom and on distal site structural organization is reported. In particular, tunnel 1 accessibility is modulated by a complex reorganization of the Trp(B9)60 and Phe(E11)93 side‐chains, triggered by mutations of the Tyr(B10)61 and Ile(G11)149 residues, and affected by the presence and type of the distal heme‐bound ligand. © 2011 IUBMB IUBMB Life, 63(5): 287–294, 2011
Endotoxin contamination delays the foreign body reaction
Authors: van Putten Sander M. , Wübben Maike , Plantinga Josée A. , Hennink Wim E. , van Luyn Marja J. A. , Harmsen Martin C.
Published: June 2011

Biomaterials are at continuous risk of bacterial contamination during production and application. In vivo, bacterial contamination of biomaterials delays the foreign body reaction (FBR). Endotoxins such as lipopolysaccharides (LPS), major constituents of the bacterial cell wall, are potent stimulators of the immune system in vitro and in vivo. In vitro, biomaterials contaminated with LPS induce the production of proinflammatory cytokines by adherent macrophages. This suggests that the presence of endotoxins on biomaterials will intensify the FBR. The effects of LPS on the course of the FBR have never been studied in vivo. In this study, the influence of LPS contamination on the FBR to subcutaneously implanted Puramatrix‐loaded hexamethylenediisocyanate‐crosslinked dermal sheep collagen (HDSC) disks was studied in rats. During the onset phase of the FBR, a massive influx of granulocytes was detected in LPS‐contaminated disks, while their presence was prolonged. IL‐10 production inside LPS‐contaminated disks was increased at days 10 and 21. Macrophage densities were not affected by the presence of LPS. However, macrophage functionality was altered: giant cell formation and biomaterial degradation were delayed by LPS‐contamination up to 21 days. On the basis of these results, we conclude that LPS delays the FBR. This finding indicates that endotoxin contamination has significant implications for the in vivo function of biomaterials and medical devices and emphasizes the importance of endotoxin testing. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.
Guided orientation of cardiomyocytes on electrospun aligned nanofibers for cardiac tissue engineering
Authors: Kai Dan , Prabhakaran Molamma P , Jin Guorui , Ramakrishna Seeram
Published: June 2011

Cardiac tissue engineering (TE) is one of the most promising strategies to reconstruct the infarct myocardium and the major challenge involves producing a bioactive scaffold with anisotropic properties that assist in cell guidance to mimic the heart tissue. In this study, random and aligned poly(ε‐caprolactone)/gelatin (PG) composite nanofibrous scaffolds were electrospun to structurally mimic the oriented extracellular matrix (ECM). Morphological, chemical and mechanical properties of the electrospun PG nanofibers were evaluated by scanning electron microscopy (SEM), water contact angle, attenuated total reflectance Fourier transform infrared spectroscopy and tensile measurements. Results indicated that PG nanofibrous scaffolds possessed smaller fiber diameters (239 ± 37 nm for random fibers and 269 ± 33 nm for aligned fibers), increased hydrophilicity, and lower stiffness compared to electrospun PCL nanofibers. The aligned PG nanofibers showed anisotropic wetting characteristics and mechanical properties, which closely match the requirements of native cardiac anisotropy. Rabbit cardiomyocytes were cultured on electrospun random and aligned nanofibers to assess the biocompatibility of scaffolds, together with its potential for cell guidance. The SEM and immunocytochemical analysis showed that the aligned PG scaffold greatly promoted cell attachment and alignment because of the biological components and ordered topography of the scaffolds. Moreover, we concluded that the aligned PG nanofibrous scaffolds could be more promising substrates suitable for the regeneration of infarct myocardium and other cardiac defects. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
Neurosteroid allopregnanolone regulates EAAC1‐mediated glutamate uptake and triggers actin changes in Schwann cells
Authors: Perego Carla , DI Cairano Eliana S. , Ballabio Marinella , Magnaghi Valerio
Published: June 2011

Recent evidence shows that neurotransmitters (e.g., GABA, Ach, adenosine, glutamate) are active on Schwann cells, which form myelin sheaths in the peripheral nervous system under different pathophysiologic conditions. Glutamate, the most important excitatory neurotransmitter, has been recently involved in peripheral neuropathies, thus prevention of its toxic effect is desirable to preserve the integrity of peripheral nervous system and Schwann cells physiology. Removal of glutamate from the extracellular space is accomplished by the high affinity glutamate transporters, so we address our studies to analyze their functional presence in Schwann cells. We first demonstrate that Schwann cells express the EAAC1 transporter in the plasma membrane and in intracellular vesicular compartments of the endocytic recycling pathways. Uptake experiments confirm its presence and functional activity in Schwann cells. Secondly, we demonstrate that the EAAC1 activity can be modulated by exposure to the neurosteroid allopregnanolone 10 nM (a progesterone metabolite proved to support Schwann cells). Transporter up‐regulation by allopregnanolone is rapid, does not involve protein neo‐synthesis and is prevented by actin depolymerization. Allopregnanolone modulation involves GABA‐A receptor and PKC activation, promotes the exocytosis of the EAAC1 transporter from intracellular stores to the Schwann cell membrane, in actin‐rich cell tips, and modifies the morphology of cell processes. Finally, we provide evidence that glutamate transporters control the allopregnanolone‐mediated effects on cell proliferation. Our findings are the first to demonstrate the presence of a functional glutamate uptake system, which can be dynamically modulated by allopregnanolone in Schwann cells. Glutamate transporters may represent a potential therapeutic target to control Schwann cell physiology. J. Cell. Physiol. 227: 1740–1751, 2012. © 2011 Wiley Periodicals, Inc.
Human dipeptidyl peptidase III: insights into ligand binding from a combined experimental and computational approach
Authors: Tomić Antonija , Abramić Marija , Špoljarić Jasminka , Agić Dejan , Smith David M. , Tomić Sanja
Published: June 2011

Human dipeptidyl peptidase III (DPP III) is a zinc‐exopeptidase with implied roles in protein catabolism, pain modulation, and defense against oxidative stress. To understand the mode of ligand binding into its active site, we performed molecular modeling, site‐directed mutagenesis, and biochemical analyses. Using the recently determined crystal structure of the human DPP III we built complexes between both, the wild‐type (WT) protein and its mutant H568N with the preferred substrate Arg‐Arg‐2‐naphthylamide (RRNA) and a competitive inhibitor Tyr‐Phe‐hydroxamate (Tyr‐Phe‐NHOH). The mutation of the conserved His568, structurally equivalent to catalytically important His231 in thermolysin, to Asn, resulted in a 1300‐fold decrease of kcat for RRNA hydrolysis and in significantly lowered affinity for the inhibitor. Molecular dynamics simulations revealed the key protein–ligand interactions as well as the ligand‐induced reorganization of the binding site and its partial closure. Simultaneously, the non‐catalytic domain was observed to stretch and the opening at the wide side of the inter‐domain cleft became enhanced. The driving force for these changes was the formation of the hydrogen bond between Asp372 and the bound ligand. The structural and dynamical differences, found for the ligand binding to the WT enzyme and the H568N mutant, and the calculated binding free energies, agree well with the measured affinities. On the basis of the obtained results we suggest a possible reaction mechanism. In addition, this work provides a foundation for further site‐directed mutagenesis experiments, as well as for modeling the reaction itself. Copyright © 2010 John Wiley & Sons, Ltd.
Reassessment of the size of the supermolecular state of Dishevelled‐3
Authors: Patel Trushar R. , Winzor Donald J.
Published: June 2011

Amendment of the interpretation of recently published size‐exclusion chromatography data for Dishevelled‐3 on Superdex 200 and Sephacryl S‐400 has led to an increase in the estimated size of the supermolecular state from 2000 to 35 000 kDa, a value that essentially duplicates the redetermined and reported estimates obtained by fluorescence correlation spectroscopy on live cells. The earlier discrepancy between the sizes of the extensively aggregated form of this scaffold protein in vivo and in vitro is thereby eliminated. Copyright © 2011 John Wiley & Sons, Ltd.
Lean strategy deployment delivers customer satisfaction at GE Healthcare
Authors: Pejsa Paul , Eng Rich
Published: June 2011

When GE Healthcare combined several service divisions to form Clinical Systems Service, it faced the challenge of unifying multiple strategies while improving customer satisfaction. Focusing on the experiences of one of those segments, Monitoring Solutions/Diagnostic Cardiology, the authors show how lean strategy deployment can be used to boost customer satisfaction by improving communications and tying daily work processes to organizational objectives. © 2011 Wiley Periodicals, Inc.
Precessional forcing of tropical vegetation carbon storage
Authors: Gosling William D. , Holden Philip B.
Published: June 2011

Since the Mid Pleistocene Revolution, which occurred about one million years ago, global temperatures have fluctuated with a quasi‐periodicity of ca. 100 ka. The pattern of past change in the extent of woodlands, and therefore by inference vegetation carbon storage, has been demonstrated to have a strong positive link with this global temperature change at high and mid latitudes. However, understanding of climate systems and ecosystem function indicates that the pattern of woodland change at low latitudes may follow a fundamentally different pattern. We present output from the intermediate complexity model GENIE‐1, comprising a single transient simulation over the last 800 ka and a 174‐member ensemble of 130 ka transient simulations over the last glacial cycle. These simulations suggest that while vegetation carbon storage in mid–high northern latitudes robustly follows the characteristic ca. 100 ka cycle, this signal is not a robust feature of tropical vegetation, which is subject to stronger direct forcing by the precessional (21 ka) orbital cycle (albeit with a highly uncertain response). We conclude that the correlation of palaeoenvironmental records from low latitudes with global temperature change must be done with caution. Copyright © 2011 John Wiley & Sons, Ltd.
Hollow fiber‐based liquid–liquid–liquid microextraction followed by flow injection analysis using column‐less HPLC for the determination of phenazopyridine in plasma and urine
Authors: Saraji Mohammad , Bidgoli Ali Akbar Hajialiakbari , Farajmand Bahman
Published: June 2011

Hollow fiber‐based liquid–liquid–liquid microextraction (HF‐LLLME) followed by flow injection analysis and diode array detection (FIA‐DAD) was applied as a simple and sensitive quantitative method for the determination of phenazopyridine in urine and plasma samples. Flow injection system included a conventional HPLC system (without a chromatographic column) and a diode array detector. The extraction of phenazopyridine was carried out using diphenyl ether as the organic phase for filling the pores of the hollow fiber wall, and 0.1 M H2SO4 solution as acceptor phase in the lumen of the fiber. The factors affecting the HF‐LLLME and flow injection analysis including type of organic solvent, pH of donor phase, extraction temperature, extraction time, stirring rate, and pH of mobile phase were investigated and the optimal extraction conditions were established. With the consumption of 5 mL of sample solution, the enrichment factor was about 230. The limit of detection was 0.5 μg/L with inter‐ and intra‐day precision being (RSD%) 6.9 and 4.9, respectively. Excellent linearity was found between 5 and 200 μg/L.
Lipid fuels for exercise
Authors: Stanley John
Published: June 2011

Most types of exercise use a combination of carbohydrate and lipid fuels. However, the proportion of the two fuels used depends on the intensity and duration of the exercise. The major advantage of lipid fuels e. g. fatty acids and lipid energy stores e. g. triacylglycerols are their energy density. Thus those forms of exercise with a long duration and a high total energy demand such as marathon running tend to use predominantly lipid fuels. The major advantage of carbohydrate fuels e. g. glucose and carbohydrate energy stores e. g. glycogen are the speed at which they can be made available. Thus those forms of exercise with a need for the rapid supply of energy over a limited period of time e. g. a 100 metre sprint tend to use predominantly carbohydrate fuels.
Milestones in ataxia
Authors: Klockgether Thomas , Paulson Henry
Published: June 2011

The past 25 years have seen enormous progress in the deciphering of the genetic and molecular basis of ataxias, resulting in improved understanding of their pathogenesis. The most significant milestones during this period were the cloning of the genes associated with the common spinocerebellar ataxias, ataxia telangiectasia, and Friedreich ataxia. To date, the causative mutations of more than 30 spinocerebellar ataxias and 20 recessive ataxias have been identified. In addition, there are numerous acquired ataxias with defined molecular causes, so that the entire number of distinct ataxia disorders exceeds 50 and possibly approaches 100. Despite this enormous heterogeneity, a few recurrent pathophysiological themes stand out. These include protein aggregation, failure of protein homeostasis, perturbations in ion channel function, defects in DNA repair, and mitochondrial dysfunction. The clinical phenotypes of the most common ataxia disorders have been firmly established, and their natural history is being studied in ongoing large observational trials. Effective therapies for ataxias are still lacking. However, novel drug targets are under investigation, and it is expected that there will be an increasing number of therapeutic trials in ataxia. © 2011 Movement Disorder Society
Milestones in gait, balance, and falling
Authors: Nutt John G. , Horak Fay B. , Bloem Bastiaan R.
Published: June 2011

Gait, balance, and falls have become increasingly common topics of published articles in the Movement Disorders journal since its launch in 1986. This growth represents an increasing awareness of the importance of mobility to patients' quality of life. New methods have become available that allow for accurate measurement of many aspects for gait and balance. This has led to new concepts of understanding gait and balance disorders. Neuroimaging has begun to reveal the neural circuitry underlying gait and balance. The physiology and pathophysiology of balance and gait are beginning to tease out the many processes involved in mobility and how they may be disrupted by disease processes. With these advances, the old therapeutic nihilism that characterized the clinician's approach to falls and gait disorders is disappearing, as innovative physiotherapy, exercise, drugs, and deep brain stimulation are being employed for gait and balance disorders. © 2011 Movement Disorder Society
Parkinson's disease: The quintessential neuropsychiatric disorder
Authors: Weintraub Daniel , Burn David J.
Published: June 2011

Although diagnosed by characteristic motor features, Parkinson's disease may be preceded, and is frequently accompanied by, a wide range of cognitive and neuropsychiatric features. In addition to the most commonly studied disorders of dementia, depression, and psychosis, other relatively common and clinically significant psychiatric complications include impulse control disorders, anxiety symptoms, disorders of sleep and wakefulness, and apathy. These problems may be underrecognized and are frequently undertreated. The emergent focus on nonmotor aspects of Parkinson's disease over the past quarter of a century is highlighted by a nonlinear increase in the number of articles published devoted to this topic. Although the development of newer antidepressants, atypical antipsychotics, and cholinesterase inhibitors in recent years has had a positive benefit on the management of these troublesome and distressing symptoms, responses are frequently suboptimal, and this remains an area of major unmet therapeutic need. © 2011 Movement Disorder Society
Milestones in myoclonus
Authors: Shibasaki Hiroshi , Thompson Philip D.
Published: June 2011

This review examines some of the advances in understanding myoclonus over the last 25 years. The classification of myoclonus into cortical, brainstem, and spinal forms has been consolidated, each with distinctive clinical characteristics and physiological mechanisms. New genetic causes of myoclonus have been identified, and the molecular basis of several of these conditions has been discovered. It is increasingly apparent that disease of the cerebellum is particularly important in the genesis of cortical reflex myoclonus. However, the precise mechanism and origin of myoclonus in many situations remain uncertain. Effective treatment of myoclonus remains limited, and the challenge lies ahead to develop more therapeutic options. © 2011 Movement Disorder Society
The Movement Disorder Society and Movement Disorders: A Modern History
Authors: Goetz Christopher G. , McGhiey Anne
Published: June 2011

The Movement Disorder Society (MDS) developed out of a merger with two short‐lived organizations, the Movement Disorder Society, primarily organized to develop a journal for the subspecialty, and the International Society of Motor Disturbances, primarily organized to develop international congresses. The formal merger of the Movement Disorder Society and the International Society of Motor Disturbances into the Movement Disorder Society took place at the 2nd International Congress of Movement Disorders in Munich, Germany, in June 1992. Whereas the journal, Movement Disorders, and the annual International Congress of Parkinson's Disease and Movement Disorders remain the anchors of the society, the goals now include the development of regional symposia, regional sections, Web‐based educational programs, and outreach efforts to include young investigators, wide international membership, and inclusion of non‐neurologists, including basic scientists, neurosurgeons, and nonphysician health professionals. Movement Disorders has a continuingly growing subscribership and rising impact factor. © 2011 Movement Disorder Society