bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal structure and intermediate-depth seismicity in the Tohoku-Hokkaido subduction zones
Authors: van Keken P. E. , Kita S. , Nakajima J.
Published: November 2012

Abstract. The cause of intermediate-depth (>40 km) seismicity in subduction zones is not well understood. The viability of proposed mechanisms, which include dehydration embrittlement, shear instabilities and the presence of fluids in general, depends significantly on local conditions, including pressure, temperature and composition. The well-instrumented and well-studied subduction zone below Northern Japan (Tohoku and Hokkaido) provides an excellent testing ground to study the conditions under which intermediate-depth seismicity occurs. This study combines new finite element models that predict the dynamics and thermal structure of the Japan subduction system with a high-precision hypocenter data base. The upper plane of seismicity is principally contained in the crustal portion of the subducting slab and appears to thin and deepen within the crust at depths >80 km. The disappearance of seismicity overlaps in most of the region with the predicted phase change of blueschist to hydrous eclogite, which forms a major dehydration front in the crust. The correlation between the thermally predicted blueschist-out boundary and the disappearance of seismicity breaks down in the transition from the northern Japan to Kurile arc below western Hokkaido. Adjusted models that take into account the seismically imaged modified upper mantle structure in this region fail to adequately recover the correlation that is seen below Tohoku and eastern Hokkaido. We conclude that the thermal structure below Western Hokkaido is significantly affected by time-dependent, 3-D dynamics of the slab. This study generally supports the role of fluids in the generation of intermediate-depth seismicity.
An ice flow modeling perspective on bedrock adjustment patterns of the Greenland ice sheet
Authors: Olaizola M. , van de Wal R. S. W. , Helsen M. M. , de Boer B.
Published: November 2012

Abstract. Since the launch in 2002 of the Gravity Recovery and Climate Experiment (GRACE) satellites, several estimates of the mass balance of the Greenland ice sheet (GrIS) have been produced. To obtain ice mass changes, the GRACE data need to be corrected for the effect of deformation changes of the Earth's crust. Recently, a new method has been proposed where ice mass changes and bedrock changes are simultaneously solved. Results show bedrock subsidence over almost the entirety of Greenland in combination with ice mass loss which is only half of the currently standing estimates. This subsidence can be an elastic response, but it may however also be a delayed response to past changes. In this study we test whether these subsidence patterns are consistent with ice dynamical modeling results. We use a 3-D ice sheet–bedrock model with a surface mass balance forcing based on a mass balance gradient approach to study the pattern and magnitude of bedrock changes in Greenland. Different mass balance forcings are used. Simulations since the Last Glacial Maximum yield a bedrock delay with respect to the mass balance forcing of nearly 3000 yr and an average uplift at present of 0.3 mm yr−1. The spatial pattern of bedrock changes shows a small central subsidence as well as more intense uplift in the south. These results are not compatible with the gravity based reconstructions showing a subsidence with a maximum in central Greenland, thereby questioning whether the claim of halving of the ice mass change is justified.
Electrochemically Deposited Gentamicin-Loaded Calcium phosphate Coatings for Bone Tissue Integration
Authors: Altomare Lina , Visai Livia , Bloise Nora , Arciola Carla Renata , Ulivi Lorenzo , Candiani Gabriele , Cigada Alberto , Chiesa Roberto , De Nardo Luigi
Published: November 2012

Purpose

Despite improvements in operative environment and surgical techniques, post-operative infections remain one of the most devastating complications in total joint replacement prostheses. Several efforts have been made to modify the surface of materials in order to prevent bacterial adhesion and colonization. Here, we show a one-pot electrochemical surface modification process for co-deposition of calcium phosphate and gentamicin, with the aim of triggering specific biological responses and imparting antibacterial properties on titanium alloy prostheses.

Methods

Gentamicin-loaded calcium phosphate coatings were deposited on Ti specimens via cathodic polarization in an electrochemical bath containing different amounts of the antibiotic salt (1–10 mg mL–1). Coatings were evaluated in terms of chemico-physical properties, via SEM/EDX, XRD, and ICP analysis, and antibacterial activity, via agar disc diffusion test on Staphylococcus aureus 8325–4 and Staphylococcus aureus SA113.

Results

An effective incorporation of gentamicin was achieved without any major effect on the morphology and structure. Morphology resulted in a typical plate-like brushite structure, confirmed by chemical composition and crystallographic structure. Gentamicin-loaded coatings showed an antibacterial efficacy on both staphlococcal strains, with a dose-dependent activity.

Conclusions

Electrochemical technology can be advantageously exploited in order to obtain coatings for bone-contact prostheses with tailored antibacterial properties.
An Opto-Structural Method to Estimate the Stress-Strain Field Induced by Cell Contraction on Substrates of Controlled Stiffness in Vitro
Authors: Raimondi Manuela Teresa , Balconi Giovanna , Boschetti Federica , Di Metri Antonio , Mohammed Salman Afroze Azmi , Quaglini Virginio , Araneo Lucio , Galvéz Beatriz G. , Lupi Monica , Latini Roberto , Remuzzi Andrea
Published: November 2012

Purpose

Mechanical properties of the extra-cellular matrix (ECM) such as stiffness mediate cell signaling, proliferation, migration, and differentiation. Within this context, we developed a method to estimate in vitro the stress-strain field induced by contraction of cardiovascular progenitor cells on substrates of controlled stiffness.

Methods

Two alginate-agarose hydrogels were polymerized and mechanically characterized under compression. The hydrogels showed different levels of stiffness, mimicking either normal or pathologic ECM of the cardiac tissue, with an average compressive equilibrium modulus of 3 and 25 kPa, respectively. To estimate substrate deformation induced by the adhering cells, fluorescent microspheres were included under the surface layer of the hydrogels as displacement trackers. The hydrogels were polymerized in multiwell plates and seeded with cells that were allowed to adhere for 24 hours. On the softer substrate, images of the substrate surface and the cells were acquired using time-lapse fluorescence microscopy. Image processing enabled tracking the microsphere movements and mapping local substrate deformation because of tensile stresses produced by the cells. The resulting tensile stresses could then be calculated from measured stiffness.

Results and Conclusions

The substrate strains ranged between a maximum contraction of –26.5% to a maximum stretching of 19.8%. The calculated stresses ranged between a maximum compression of –0.53 kPa to a maximum tension of 0.4 kPa (nN/μm2). These results may help to interpret experimental findings, showing important differences in cell morphology and expression of phenotypic markers, induced by culturing cells on substrates with different mechanical properties.
Combining coordination mechanisms to improve performance in multi-robot teams
Authors: Nasroullahi Ehsan , Tumer Kagan
Published: November 2012

Coordination is essential to achieving good performance in cooperative multiagent systems. To date, most work has focused on either implicit or explicit coordination mechanisms; while relatively little work has focused on the benefits of combining these two approaches. In this work we demonstrate that combining explicit and implicit mechanisms can significantly improve coordination and system performance over either approach individually. First, we use difference evaluations (which aim to compute an agent’s contribution to the team) and stigmergy to promote implicit coordination. Second, we introduce an explicit coordination mechanism dubbed intended Destination Enhanced Artificial State (IDEAS), where an agent incorporates other agents’ intended destinations directly into its state. The IDEAS approach does not require any formal negotiation between agents, and is based on passive information sharing. Finally, we combine these two approaches on a variant of a team-based multi-robot exploration domain, and show that agents using a both explicit and implicit coordination outperform other learning agents up to 25%.
The application of Gaussian processes in the predictions of permeability across mammalian and polydimethylsiloxane membranes
Authors: Sun Yi , Adams Rod , Davey Neil , Moss Gary P. , Prapopopolou Maria , Brown Marc B. , Martin Gary P. , Wilkinson Simon C.
Published: November 2012

The problem of predicting the rate of percutaneous absorption of a drug is an important issue, particular with the increasing use of the skin as a means of moderating and controlling drug delivery. One key feature of this problem domain is that human skin permeability to penetrants (often characterised by Kp, the permeability coefficient) has been shown to be inherently non-linear when mathematically related to the key physicochemical parameters of penetrants. The aims of the current study were to apply and validate Gaussian process regression methods to datasets for membranes other than human skin, and to explore how the nature of the dataset may influence its analysis. Permeability data for absorption across rodent and pig skin, and polydimethylsiloxane Silastic® membranes was collected from the literature. Two QSPR methods were applied to compare to the Gaussian process models. The results demonstrated that Gaussian process models with different covariance functions outperform the QSPR model for human, pig and rodent datasets, but in general are not good for Silastic® membranes. These results suggest that the physicochemical parameters employed in this study might not be appropriate for developing models that represent this membrane. In addition, the results show the size of the datasets, in both absolute and comparative senses, appears to influence model quality.
Mayor: The Strongest Player in Slovenian Local Government?
Authors: Kukovič Simona , Haček Miro , Grabner Anja
Published: November 2012

The paper analyses the position and role of the mayor in the Slovenian system of local self-government. This role has changed significantly since the communist times, and even since the mid-1990s, when Slovenia re-introduced the system of local self-government. We track these changes and analyse them in this paper. Our theoretical anchor is the work by Mouritzen and Svara (2002), in which they categorise ideal-type models of executive government at the sub-national levels of government and the relations inside the executive. Using data gathered in 2011 and 2012 in a majority of Slovenian municipalities, we analyse the governing of the mayor and try to ascertain the extent to which it depends on the political parties that constitute municipal councils, on the municipal administration, and also on the institutional framework within which municipal governments function.
China and Africa development relations – from the Washington concensus to Beijing concensus
Authors: Piknerová Linda
Published: November 2012

This study deals with the issue of development relations between China and Africa in the context of the Beijing concensus. It attempts to provide an analysis of Chinese foreign policy since the beginning of the 90’s. The text is divided into three basic parts. The first contains discussion on the theories of development, including the main features of the (post)Washington concensus based on liberalism, decentralization and privatization, followed by the Beijing concensus representing the counter-paradigm. The second focuses on the historical roots of bilateral relations since the beginning of the 20th century until the end of the Cold War. TAZARA, the Tanzania-Zambia railway built by China is chosen as the most representative example of Chinese foreign policy during the Cold War period. The last part deals with current relations influenced by Chinese oil diplomacy and the so-called one-China policy. Sudan and Angola are chosen as significant examples of African states in which China is involved.
Women in Local Politics – A Case Study of Municipalities of up to Three Thousand Inhabitants in the Moravian-Silesian Region
Authors: Sztwiertnia Radomír , Hellová Dana
Published: November 2012

The inadequate representation of women at various levels of politics is a much discussed topic among politicians and the public. Socio-economic, institutional and cultural factors are often perceived as the main reasons which influence the supply and demand sides of political competition. In Czech local politics, the situation seems to be more propitious. The proportion of women in municipal assemblies is significantly higher, which brings us to the question of the influence of traditional barriers to women‘s decisions to enter politics. On the basis of quantitative research among representatives of municipalities of up to three thousand inhabitants in the Moravian-Silesian Region, we conclude that the defined barriers are present; however, their influence on the decision of women to enter politics is weakening.
Topography of Lobbying Regulation
Authors: Kubová Radana , Pitrová Markéta
Published: November 2012

The aim of this article is to underline a more broad and complex approach towards the regulation of lobbying. Our objective here is to provide a systematic enumeration of possible regulatory alternatives. This research involves the examination of the most notable and significant cases of lobbying regulation in the western world and is based largely on the textual analysis of relevant regulatory documents. We do not, however, intend to present the detailed mapping of lobbying regulation in all possible arenas, or evaluate these means, or even recommend particular regulatory options or instruments. We therefore suggest an analytical framework highlighting three important points that should be clarified in each regulatory system: 1) the actors involved in lobbying, 2) the form of regulation, and 3) the regulatory means and instruments. The proposed topography of lobbying regulation can serve as a general basis for the further analysis of regulatory schemes and their comparison, but also as a guide for those considering regulatory options.
Globalizace, demokracie a terorismus
Authors: Jaroš Tomáš
Published: November 2012

Hobsbawm, Eric. 2009. Globalizace, demokracie a terorismus. Praha: Nakladatelství Academia, 136 pages.
Krajní pravice a krajní levice v ČR
Authors: Walach Václav
Published: November 2012

Bastl, Martin; Mareš, Miroslav; Smolík, Josef a Vejvodová, Petra. 2011. Krajní pravice a krajní levice v ČR, Praha: Grada Publishing, a. s., 288 pages.
Should Religious Symbols be Allowed on Public Land?
Authors: Matušinová Anna
Published: November 2012

Gerdes, Louise I. (eds.). 2011. Should Religious Symbols be Allowed on Public Land? Greenhaven Press: Gale Cengage Learning, 1st edition, 126 pages.
Incidences de Gould auprès de compositeurs, interprètes et réalisateurs
Authors: Gervasi Flavia
Published: November 2012

Le double anniversaire – de la naissance et de la mort – de Glenn Gould offre l’occasion de réfléchir sur l’influence qu’il a exercée sur les nouvelles générations quant aux différents champs de la production musicale, et de faire un bilan de l’héritage qu’il leur a légué. Pour ce faire, nous avons mené une enquête à laquelle ont participé, par courriel, au cours du printemps 2012, sept personnalités du monde musical qui ont eu un contact direct avec Gould ou qui entretiennent un lien particulier avec sa production et ses oeuvres. Il s’agit de Kevin Bazzana, David Jaeger, alcides lanza, Friedemann Sallis, Gayle Young, Louis Dufort et Georges Guillard. Les questions ont été mises au point par la rédaction de Circuit, ensuite assemblées et commentées par l’auteure. Ce travail, conçu comme une contribution polyphonique, a stimulé des réponses intéressantes et variées au sujet des répercussions de l’oeuvre du musicien canadien sur les acteurs de la scène musicale contemporaine. Au-delà des approches et conclusions hétérogènes, les participants reconnaissent à Glenn Gould le mérite d’avoir imposé un questionnement esthétique et sociologique incontournable sur le rapport du musicien classique avec la technologie, questionnement nécessaire pour comprendre en profondeur comment pratiquer la musique au xxie siècle, et l’écouter.
Le sérialisme lyrique de la « Devinette de la guitare » (1954) de Serge Garant
Authors: Bazin Paul
Published: November 2012

La mélodie « Devinette de la guitare », tirée du cycle Caprices que composa Serge Garant en 1954, est un exemple éloquent de la fascination qu’exerçait sur le compositeur la rigueur de la construction musicale. Premiers opus entièrement sériels de son catalogue, les mélodies du cycle Caprices témoignent à la fois de la manipulation virtuose que fait Garant de son matériau sonore, ainsi que du lyrisme abstrait qui caractérise sa démarche.
Hierarchical FAU‐ and LTA‐Type Zeolites by Post‐Synthetic Design: A New Generation of Highly Efficient Base Catalysts
Authors: Verboekend Danny , Keller Tobias C. , Mitchell Sharon , Pérez‐Ramírez Javier
Published: November 2012

Hierarchical FAU‐ and LTA‐type catalysts are prepared by post‐synthetic modifications and evaluated in the base‐catalyzed Knoevenagel condensation of benzaldehyde with malononitrile. A novel route to attain mesoporous Al‐rich zeolites (A and X) is demonstrated, while mesoporous Y and USY zeolites are prepared using recently developed methods. Base functionality is introduced by alkali ion exchange (Cs, Na) or by high‐temperature nitridation in ammonia. A thorough characterization of the zeolites' structure, composition, porosity, morphology, and basicity demonstrates that the presence of a secondary mesopore network enhances the ion‐exchange efficiency and the structural incorporation of nitrogen. The modified USY zeolites display twice the conversion, while the hierarchical A, X, and Y are up to 10 times more active based on the enhanced accessibility. These results demonstrate that the Knoevenagel condensation takes place predominately at the external surface, highlighting secondary porosity as a key criterion in the design of basic zeolite catalysts.
First birth interval, an indicator of energetic status, is a predictor of lifetime reproductive strategy
Authors: Nenko Ilona , Jasienska Grazyna
Published: November 2012

Objectives:

Women should differ in their reproductive strategies according to their nutritional status. We tested a hypothesis that women who have a good nutritional status early in life, as indicated by a shorter waiting time to the first birth (first birth interval, FBI), are able to afford higher costs of reproduction than women who have worse nutritional condition.

Methods:

We collected data on 377 women who got married between the years 1782 and 1882 in a natural fertility population in rural Poland. The study group was divided into tertiles based on the length of FBI.

Results:

Women with the shortest FBI had a higher number of children (P = 0.005), higher number of sons (P = 0.01), and shorter mean interbirth intervals (P = 0.06). Women who had ever given birth to twins had shorter FBI than women of singletons (20.1 and 26.1 months, respectively; P = 0.049). Furthermore, women with a shorter FBI, despite having higher costs of reproduction, did not have a different lifespan than women with a longer FBI.

Conclusions:

Our results suggest that women who were in better energetic condition (shorter length of FBI), achieved higher reproductive success without reduction in lifespan. FBI reflects interindividual variation, which may result from variation in nutritional status early in life and thus may be a good predictor of subsequent reproductive strategy. We propose to use FBI as an indicator of women's nutritional status in studies of historical populations, especially when information about social status is not available. Am. J. Hum. Biol., 2013. © 2012 Wiley Periodicals, Inc.
Factors that Influence Stereoselectivity in Proline‐Catalyzed Mannich Reactions
Authors: Parasuk Waraporn , Parasuk Vudhichai
Published: November 2012

The stereoselectivity of the Mannich reaction of cyclohexanone, formaldehyde, and aniline catalyzed by (S)‐thiazolidine‐4‐carboxylic acid and (S)‐5,5‐dimethylthiazolidine‐4‐carboxylic acid (referred to hereafter as “thioproline” and “5,5‐dimethylthioproline” for short) were investigated theoretically by using B3LYP/6‐31++G(d,p) calculations. The stereocontrol in the thioproline‐catalyzed reaction originates from the reaction between the enamine and the imine to produce S‐ or R‐configured iminium‐ion intermediates. Apart from anti/syn conformations, the pucker of the five‐membered ring is also a critical factor for the stereoselectivity. For thioproline, the reaction barriers of the S pathway with d and u ring puckers are 3.3 and 4.7 kcal mol−1 lower than the corresponding R pathway. With a de ring pucker, smaller S/R barrier differences were calculated. For dimethylthioproline, the S/R barrier difference is larger with d and u ring puckers. Dimethylsulfoxide as a solvent reduces the free energy barriers of the R pathway for the thioproline‐ and dimethylthioproline‐catalyzed reactions. The ring pucker and the solvent dictate the stereoselectivity of thioproline‐catalyzed Mannich reactions.
Is nasal packing necessary after septoplasty? A meta‐analysis
Authors: Banglawala Sarfaraz M. , Gill Mandeep , Sommer Doron D. , Psaltis Alkis , Schlosser Rodney , Gupta Michael
Published: November 2012

Background

Nasal packing is routinely used after septoplasty because it is believed to decrease risk of postoperative bleeding, hematomas, and adhesions. Multiple studies have shown, however, that there are numerous complications associated with nasal packing. The purpose of this work was to perform a meta‐analysis on the existing literature to evaluate the role of nasal packing after septoplasty.

Methods

Two independent reviewers conducted a literature search using EMBASE, OVID, Medline, PubMed, Google scholar, Cochrane Library, and reference list review from 1966 to August 2010 to identify studies assessing nasal packing after septoplasty. All papers were reviewed for study design, results, and were assigned an Oxford level of evidence grade, Detsky score, and Methodological Index for Nonrandomized Studies (MINORS) score.

Results

Sixteen papers were identified that met the inclusion criteria. Eleven papers were randomized control trials, 3 were prospective, and 2 were retrospective studies. Nasal packing did not show benefit in reducing postoperative bleeding, hematomas, septal perforations, adhesions, or residual deviated nasal septum. There was, however, an increase in postoperative infections. Two studies using fibrin products as nasal packing showed a decreased bleeding rate.

Conclusion

Nasal packing after septoplasty does not show any postoperative benefits. Fibrin products show a possibility of decreasing postoperative bleeding. Routine use of nasal packing after septoplasty is not warranted. This is the first meta‐analysis conducted on this topic.
Correlation of the Kennedy Osteitis Score to clinico‐histologic features of chronic rhinosinusitis
Authors: Snidvongs Kornkiat , McLachlan Rohan , Sacks Raymond , Earls Peter , Harvey Richard J.
Published: November 2012

Background

Osteitis is a feature of chronic rhinosinusitis (CRS) and often associated with recalcitrant disease. Radiological characteristics of osteitic sinus changes are commonly reported in practice but the clinical and pathologic significance is poorly defined. The objective of this study was to correlate the Kennedy Osteitis Score (KOS) to clinico‐histologic features of CRS.

Methods

A cross‐sectional study of CRS patients undergoing sinus surgery was conducted. Osteitis was scored radiologically using the KOS. Associations between osteitis and histopathology, symptoms, 22‐item Sino‐Nasal Outcomes Test (SNOT‐22), endoscopy, computed tomography (CT) mucosal score, and seromarkers were assessed. Interobserver correlation coefficient was performed. Additionally, the KOS was correlated to an alternate Global Osteitis Score.

Results

A total of 88 patients were assessed (45.5% female, age 50.3 ± 13.6 years); 45 (51.1%) patients had osteitis. Patients with KOS >0, had greater endoscopy score (6.1 ± 2.9 vs 4.4 ± 3.6, p = 0.03) and CT score (14.0 ± 6.0 vs 10.1 ± 5.7, p < 0.01) than those without osteitis. There was no difference in symptom score (2.4 ± 1.3 vs 2.4 ± 1.1, p = 0.89) and SNOT‐22 (2.0 ± 1.0 vs 1.9 ± 1.1, p = 0.56) in patients with and without osteitis. KOS was higher in patients with tissue eosinophilia >10/high‐power field (HPF) (median 3.0 [IQR, 1.0–5.3] vs 0.0 [0.0–4.0], p = 0.03) and serum eosinophilia >0.3 × 109/L (4.0 [2.0–7.0] vs 1.0 [0.0–4.0], p < 0.01). Importantly, this was also true for those without prior surgery. The interobserver correlation coefficient was good (R = 0.86, p < 0.001). There was a significant correlation between the KOS and the Global Osteitis Score (R = 0.93, p < 0.001).

Conclusion

The KOS is a simple, easy, and reproducible scale in assessing osteitic bones in patients with CRS and can predict measures of severity in eosinophilic rhinosinusitis.
Noninvasive Staphylococcus aureus biofilm determination in chronic rhinosinusitis by detecting the exopolysaccharide matrix component poly‐N‐acetylglucosamine
Authors: Foreman Andrew , Jervis‐Bardy Josh , Boase Samuel J. , Tan Lorwai , Wormald Peter‐John
Published: November 2012

Background

The role that bacterial biofilms might play in recalcitrant forms of chronic rhinosinusitis (CRS) is increasingly being recognized. However, the detection of bacteria existing in this form, using standard culture, is limited by their unique metabolically inactive properties. All current biofilm diagnostic modalities require invasive mucosal biopsies, which limit their use to the operating theatre.

Methods

Twenty CRS patients and 5 controls were enrolled in a prospective study to assess the feasibility of noninvasively diagnosing S. aureus biofilms by detecting the biofilm matrix polysaccharide poly‐N‐acetylglucosamine (PNAG). An immunofluorescence protocol was developed for PNAG detection and compared with both standard microbiological cultures and fluorescence in situ hybridization (FISH).

Results

Thirteen of 20 CRS patients had evidence of S. aureus biofilm formation using FISH. Of these, 12 had detectable PNAG. Interestingly none of the S. aureus FISH‐negative patients were PNAG‐positive despite the presence of coagulase‐negative Staphylococci biofilms, some of which may exhibit PNAG in their pathogenic forms. The development of a noninvasive S. aureus biofilm diagnostic test provides a reliable means to identify a high‐risk group of CRS patients who harbor S. aureus biofilms. The ability to be used outside of the perioperative period to assess surgical efficacy, guide management, and evaluate new treatment modalities provides a significant advance in this field of research and clinical practice.

Conclusion

This study has confirmed the feasibility of noninvasive detection of S. aureus biofilms with a simple test that produces results comparable to the more invasive methods that are currently relied upon.
Numerical investigation of the effect of the heterogeneous reaction model on the thermal behavior of pulverized coal combustion
Authors: Nozawa Sohey , Matsushita Yohsuke
Published: November 2012

To achieve high efficiency in pulverized coal combustion furnace and burner, the detailed estimation of the burn‐off time and thermal behavior of pulverized coal particles is important. The volume reaction and unreacted core models have been employed as solid–gas reaction model for a pulverized coal particle. Moreover, the possibility that the heat of reaction generated on the particle surface does not fully contribute as heating source to the coal particle should be considered. In this study, the heat and mass transfer around a single pulverized coal char particle exposed to a simplified heating environment are numerically analyzed to investigate the influence of the different coal ranks in their reactivity, coal char particle diameter, and reaction models for the burn‐off time and thermal behavior of the pulverized coal particle. From the sensitivity analysis of the reaction models for the burn‐off time, the importance of model selection when dealing the coal char particle with high reaction rates is indicated. © 2012 Curtin University of Technology and John Wiley & Sons, Ltd.
Squaric Acid Mediated Chemoselective PEGylation of Proteins: Reactivity of Single‐Step‐Activated α‐Amino Poly(ethylene glycol)s
Authors: Dingels Carsten , Wurm Frederik , Wagner Manfred , Klok Harm‐Anton , Frey Holger
Published: November 2012

The covalent attachment of poly(ethylene glycol) (PEG) to therapeutically active proteins (PEGylation) has become an important method to deal with the pharmacological difficulties of these polypeptides, such as short body‐residence times and immunogenicity. However, the derivatives of PEG used for PEGylation lack further functional groups that would allow the addition of targeting or labeling moieties. Squaric acid diethyl ester was used for the chemoselective single‐step activation of poly(ethylene glycol)s into the respective ester amides. The resultant selective protein‐reactive poly(ethylene glycol)s were investigated with respect to their selectivity towards amino acid residues in bovine serum albumin (as a model protein). The presented procedure relies on a robust two‐step protocol and was found to be selective towards lysine residues; the activated polyethers are efficient and stoichiometric PEGylation agents with a remarkable hydrolytic stability over a period of several days. By adjusting the pD value of the conjugation mixture, the chemoselectivity of the activated PEGs towards the α‐ and ε‐amino groups of lysine methyl ester was effectively changed.
Boronium‐Cation‐Based Ionic Liquids as Hypergolic Fluids
Authors: Wang Kai , Zhang Yanqiang , Chand Deepak , Parrish Damon A. , Shreeve Jean'ne M.
Published: November 2012

Two series of boronium‐cation‐based ionic liquids were prepared and fully characterized by 1H, 13C, and 11B NMR and infrared spectroscopy, differential scanning calorimetry (DSC), and elemental analysis. The structure of bis(1‐methyl‐1H‐imidazole‐3‐yl)dihydroboronium dicyanoborohydride (5 a) was determined by single‐crystal X‐ray diffraction. The densities of these ionic liquids range from 1.05 to 1.28 g cm−3, and the heats of formation, predicted on the basis of Gaussian 03 calculations, fall between −164.6 and 430.5 kJ mol−1. Compound 5 b, bis(1‐allyl‐1H‐imidazole‐3‐yl)dihydroboronium dicyanoborohydride, exhibits the lowest viscosity (35 mPa s) and shortest ignition‐delay time (14 ms) in combination with 100 % HNO3.
IR‐Monitored Photolysis of CO‐Inhibited Nitrogenase: A Major EPR‐Silent Species with Coupled Terminal CO Ligands
Authors: Yan Lifen , Pelmenschikov Vladimir , Dapper Christie H. , Scott Aubrey D. , Newton William E. , Cramer Stephen P.
Published: November 2012

Fourier transform infrared spectroscopy (FTIR) was used to observe the photolysis and recombination of a new EPR‐silent CO‐inhibited form of α‐H195Q nitrogenase from Azotobacter vinelandii. Photolysis at 4 K reveals a strong negative IR difference band at $\tilde \nu $=1938 cm−1, along with a weaker negative feature at 1911 cm−1. These bands and the associated chemical species have both been assigned the label “Hi‐3”. A positive band at $\tilde \nu $=1921 cm−1 was assigned to the “Lo‐3” photoproduct. By using an isotopic mixture of 12C 16O and 13C 18O, we show that the Hi‐3 bands arise from coupling of two similar CO oscillators with one uncoupled frequency at approximately $\tilde \nu $=1917 cm−1. Although in previous studies Lo‐3 was not observed to recombine, by extending the observation range to 200–240 K, we found that recombination to Hi‐3 does indeed occur, with an activation energy of approximately 6.5 kJ mol−1. The frequencies of the Hi‐3 bands suggest terminal CO ligation. This hypothesis was tested with DFT calculations on models with terminal CO ligands on Fe2 and Fe6 of the FeMo‐cofactor. An S=0 model with both CO ligands in exo positions predicts symmetric and asymmetric stretches at $\tilde \nu $=1938 and 1909 cm−1, respectively, with relative band intensities of about 3.5:1, which is in good agreement with experiment. From the observed IR intensities, Hi‐3 was found to be present at a concentration about equal to that of the EPR‐active Hi‐1 species. The relevance of Hi‐3 to the nitrogenase catalytic mechanism and its recently discovered Fischer–Tropsch chemistry is discussed.
Chiral Supramolecular Switches Based on (R)‐Binaphthalene–Bipyridinium Guests and Cucurbituril Hosts
Authors: Gao Chao , Silvi Serena , Ma Xiang , Tian He , Credi Alberto , Venturi Margherita
Published: November 2012

We designed and synthesized the three molecular tweezers1 a–c4+containing an electron acceptor 4,4′‐bipyridinium (BPY2+) unit in each of the two arms and an (R)‐2,2′‐dioxy‐1,1′‐binaphthyl (BIN) unit that plays the role of chiral centre and the hinge of the structure. Each BPY2+unit is connected to the BIN hinge by an alkyl chain formed by two‐ (1 a4+), four‐ (1 b4+), or six‐CH2(1 c4+) groups. The behavior of1 a–c4+upon chemical or photochemical reduction in the absence and in the presence of cucurbit[8]uril (CB[8]) or cucurbit[7]uril (CB[7]) as macrocyclic hosts for the bipyridinium units has been studied in aqueous solution. A detailed analysis of the UV/Vis absorption and circular dichroism (CD) spectra shows that the helicity of the BIN unit can be reversibly modulated by reduction of the BPY2+units, or by association with cucurbiturils. Upon reduction of1 a–c4+compounds, the formed BPY+.units undergo intramolecular dimerization with a concomitant change in the BIN dihedral angle, which depends on the length of the alkyl spacers. The alkyl linkers also play an important role in association to cucurbiturils. Compound1 a4+, because of its short carbon chain, associates to the bulky CB[8] in a 1:1 ratio, whereas in the case of the smaller host compound CB[7] a 1:2 complex is obtained. Compounds1 b4+and1 c4+, which have longer linkers, associate to two cucurbiturils regardless of their sizes. In all cases, association with CB[8] causes an increase of the BIN dihedral angle, whereas the formation of CB[7] complexes causes an angle decrease. Reduction of the CB[8] complexes results in an enhancement of the BPY+.dimerization with respect to free1 a–c4+and causes a noticeable decrease of the BIN dihedral angle, because the BPY+.units of the two arms have to enter into the same macrocycle. The dimer formation in the CB[8] complexes characterized by a 1:2 ratio implies the release of one macrocycle showing that the binding stoichiometry of these host–guest complexes can be switched from 1:2 to 1:1 by changing the redox state of the guest. When the reduction is performed on the CB[7] complexes, dimer formation is totally inhibited, as expected because the CB[7] cavity cannot host two BPY+.units.
Total Synthesis of (−)‐Zampanolide and Structure–Activity Relationship Studies on (−)‐Dactylolide Derivatives
Authors: Zurwerra Didier , Glaus Florian , Betschart Leo , Schuster Julia , Gertsch Jürg , Ganci Walter , Altmann Karl‐Heinz
Published: November 2012

A new total synthesis of the marine macrolide (−)‐zampanolide (1) and the structurally and stereochemically related non‐natural levorotatory enantiomer of (+)‐dactylolide (2), that is, ent‐2, has been developed. The synthesis features a high‐yielding, selective intramolecular Horner–Wadsworth–Emmons (HWE) reaction to close the 20‐membered macrolactone ring of 1 and ent‐2. The β‐keto phosphonate/aldehyde precursor for the ring‐closure reaction was obtained by esterification of a ω‐diethylphosphono carboxylic acid fragment and a secondary alcohol fragment incorporating the THP ring that is embedded in the macrocyclic core structure of 1 and ent‐2. THP ring formation was accomplished through a segment coupling Prins‐type cyclization. Employing the same overall strategy, 13‐desmethylene‐ent‐2 as well as the monocyclic desTHP derivatives of 1 and ent‐2 were prepared. Synthetic 1 inhibited human cancer cell growth in vitro with nM IC50 values, while ent‐2, which lacks the diene‐containing hemiaminal‐linked side chain of 1, is 25‐ to 260‐fold less active. 13‐Desmethylene‐ent‐2 as well as the reduced versions of ent‐2 and 13‐desmethylene‐ent‐2 all showed similar cellular activity as ent‐2 itself. The same activity level was attained by the monocyclic desTHP derivative of 1. Oxidation of the aldehyde functionality of ent‐2 gave a carboxylic acid that was converted into the corresponding N‐hexyl amide. The latter showed only μM antiproliferative activity, thus being several hundred‐fold less potent than 1.
Mixed (PS/PO)‐Stabilized Geminal Dianion: Facile Diastereoselective Intramolecular CH Activations by a Related Ruthenium–Carbene Complex
Authors: Heuclin Hadrien , Le Goff Xavier F. , Mézailles Nicolas
Published: November 2012

A new unsymmetrical geminal dianion that contained both a phosphine oxide moiety and a phosphine sulfide moiety has been synthesized. Its reactivity towards RuII was explored, which led to the formation of a highly reactive carbene complex that evolved at room temperature to yield a kinetic orthometalated RuII complex through CH activation of the phenyl group of the phosphine oxide moiety. This insertion was found to be thermally reversible and a second CH insertion occurred at a phenyl group of the phosphine sulfide moiety to form the thermodynamic orthometalated RuII complex in a diastereospecific manner. DFT calculations fully rationalized the experimental findings in terms of the relative energies of the kinetic and thermodynamic products and allowed the mechanism of this process to be fully understood.
Copper, BDNF and Its N‐terminal Domain: Inorganic Features and Biological Perspectives
Authors: Travaglia Alessio , La Mendola Diego , Magrì Antonio , Nicoletti Vincenzo Giuseppe , Pietropaolo Adriana , Rizzarelli Enrico
Published: November 2012

Brain‐derived neurotrophic factor (BDNF) is a neurotrophin that influences development, maintenance, survival, and synaptic plasticity of central and peripheral nervous systems. Altered BDNF signaling is involved in several neurodegenerative disorders including Alzheimer’s disease. Metal ions may influence the BDNF activity and it is well known that the alteration of Cu2+ homeostasis is a prominent factor in the development of neurological pathologies. The N‐terminal domain of BDNF represents the recognition site of its specific receptor TrkB, and metal ions interaction with this protein domain may influence the protein/receptor interaction. In spite of this, no data inherent the interaction of BDNF with Cu2+ ions has been reported up to now. Cu2+ complexes of the peptide fragment BDNF(1–12) encompassing the sequence 1–12 of N‐terminal domain of human BDNF protein were characterized by means of potentiometry, spectroscopic methods (UV/Vis, CD, EPR), parallel tempering simulations and DFT‐geometry optimizations. Coordination features of the acetylated form, Ac‐BDNF(1–12), were also characterized to understand the involvement of the terminal amino group. Whereas, an analogous peptide, BDNF(1–12)D3N, in which the aspartate residue was substituted by an asparagine, was synthesized to provide evidence on the possible role of carboxylate group in Cu2+ coordination. The results demonstrated that the amino group is involved in metal binding and the metal coordination environment of the predominant complex species at physiological pH consisted of one amino group, two amide nitrogen atoms, and one carboxylate group. Noteworthy, a strong decrease of the proliferative activity of both BDNF(1–12) and the whole protein on a SHSY5Y neuroblastoma cell line was found after treatment in the presence of Cu2+. The effect of metal addition is opposite to that observed for the analogous fragment of nerve growth factor (NGF) protein, highlighting the role of specific domains, and suggesting that Cu2+ may drive different pathways for the BDNF and NGF in physiological as well as pathological conditions.
Flexible, Scalable and Configurable Single‐Use Systems for Biopharmaceutical Research and Manufacture
Authors: Szarafinski Detlev
Published: November 2012

Single‐use (SU) components are a common standard in the biopharmaceutical industry. Mixing units for buffer and media preparation, bioreactors for cell cultivation, bags for storage of liquids etc. have meanwhile become integral SU components within many biopharmaceutical manufacturing processes. However, there is still a lack of SU systems incorporating multiple process steps into a SU system which constitutes a dedicated unit operation for research and development and production of e.g. monoclonal antibodies. The FlexAct® approach fills this gap and has been developed to supply scalable and configurable SU systems for upstream‐ and downstream processing. Typical unit operations are, e.g., buffer and media preparation, cell harvest, virus inactivation and ultrafiltration.
How is 68Ga Labeling of Macrocyclic Chelators Influenced by Metal Ion Contaminants in 68Ge/68Ga Generator Eluates?
Authors: Šimeček Jakub , Hermann Petr , Wester Hans‐Jürgen , Notni Johannes
Published: November 2012

To assess the influence of Zn2+, Cu2+, Fe3+, Al3+, TiIV, and SnIV on incorporation of 68Ga3+ into pendant‐arm macrocyclic chelators, the 68Ga labeling of 1,4,7‐triazacyclononane‐1,4,7‐triacetic acid (NOTA), 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA), 1,4,7‐triazacyclononane‐1,4,7‐tris[methyl(2‐carboxyethyl)phosphinic acid]) (TRAP), and 1,4,7‐triazacyclononane‐1‐[methyl(2‐carboxyethyl)phosphinic acid]‐4,7‐bis[methyl(2‐hydroxymethyl)phosphinic acid] (NOPO), as well as their peptide conjugates, was investigated in the presence of varying concentrations of these metal ions. The 68Ga labeling yield for carboxylate‐type chelators NOTA and DOTA is decreased at lower metal ion contaminant concentrations compared with phosphinate‐type chelators TRAP and NOPO. The latter are able to rapidly exchange coordinated ZnII with 68Ga3+, as confirmed by mass spectrometry and 31P NMR spectroscopy. 68Ga labeling of ZnII complexes of TRAP and NOPO proceeds as efficient as labeling of neat NOTA; this applies also to the corresponding peptide conjugates of these chelators. This behavior results in substantially improved selectivity for Ga3+ and, therefore, in more robust and reliable 68Ga labeling procedures. In addition, none of the investigated chelators binds 68Ge, rendering post‐labeling purification protocols, for example, solid‐phase extraction, a reliable means of removal of 68Ge contamination from 68Ga radiopharmaceuticals.
Isolation of erythrocytes infected with viable early stages of Plasmodium falciparum by flow cytometry
Authors: Philipp Stephan , Oberg Hans‐Heinrich , Janssen Ottmar , Leippe Matthias , Gelhaus Christoph
Published: November 2012

The erythrocytic life cycle of Plasmodium falciparum is highly associated with severe clinical symptoms of malaria that causes hundreds of thousands of death each year. The parasite develops within human erythrocytes leading to the disruption of the infected red blood cell (iRBC) prior to the start of a new cycle of erythrocyte infection. Emerging mechanisms of resistance against antimalarial drugs require improved knowledge about parasite's blood stages to facilitate new alternative antimalarial strategies. For the analysis of young blood stages of Plasmodium at the molecular level, the isolation of ring stages is essential. However, early stages can hardly be separated from both, late stages and non‐infected red blood cells using conventional methods. Here, iRBCs were stained with the DNA‐binding dyes Vybrant® DyeCycle™ Violet and SYBR® Green I. Subsequently, cells were subjected to flow‐cytometric analysis. This enabled the discrimination of early stage iRBCs as well as late‐stage iRBCs from non‐infected erythrocytes and the properties of the used dyes were evaluated. Moreover, early stage iRBCs were isolated with high purity (>98%) by FACS. Subsequently, development of sorted early stages of the parasite was monitored over time and compared with control cultures. The described flow cytometry method, based on staining with Vybrant DyeCycle Violet, allows the isolation of viable ring stages of the malarial agent P. falciparum, and thereby provides the basis for new, broad‐range molecular investigations of the parasite. © 2012 International Society for Advancement of Cytometry
Aberrant antibody affinity selection in SHIP‐deficient B cells
Authors: Leung Wai‐Hang , Tarasenko Tatiana , Biesova Zuzana , Kole Hemanta , Walsh Elizabeth R. , Bolland Silvia
Published: November 2012

The strength of the Ag receptor signal influences development and negative selection of B cells, and it might also affect B‐cell survival and selection in the GC. Here, we have used mice with B‐cell‐specific deletion of the 5′‐inositol phosphatase SHIP as a model to study affinity selection in cells that are hyperresponsive to Ag and cytokine receptor stimulation. In the absence of SHIP, B cells have lower thresholds for Ag‐ and interferon (IFN)‐induced activation, resulting in augmented negative selection in the BM and enhanced B‐cell maturation in the periphery. Despite a tendency to spontaneously downregulate surface IgM expression, SHIP deficiency does not alter anergy induction in response to soluble hen‐egg lysozyme Ag in the MDA4 transgenic model. SHIP‐deficient B cells spontaneously produce isotype‐switched antibodies; however, they are poor responders in immunization and infection models. While SHIP‐deficient B cells form GCs and undergo mutation, they are not properly selected for high‐affinity antibodies. These results illustrate the importance of negative regulation of B‐cell responses, as lower thresholds for B‐cell activation promote survival of low affinity and deleterious receptors to the detriment of optimal Ab affinity maturation.
Dinuclear Macrocyclic Palladium Dithiocarbamates Derived from the Homologous Series of Aliphatic 1,x‐Diamines (x = 4–10)
Authors: Torres‐Huerta Aarón , Höpfl Herbert , Tlahuext Hugo , Hernández‐Ahuactzi Irán F. , Sánchez Mario , Reyes‐Martínez Reyna , Morales‐Morales David
Published: November 2012

Seven dinuclear macrocyclic palladium(II) dithiocarbamates have been prepared from a homologous series of aliphatic 1,x‐diamines (x = 4–10); the objective was to vary systematically the size of the cavity. The resulting complexes were characterized by IR and NMR (1H, 13C) spectroscopy, high‐resolution FAB mass spectrometry, and in one case additionally by single‐crystal X‐ray diffraction analysis. Geometry‐optimizations using the B3LYP functional in combination with the def2‐SVP basis set were performed for the complete series of 22‐ to 36‐membered macrocycles and showed that these can be divided into two classes. Palladium(II) dithiocarbamates with an even number of methylene spacer groups yield macrocycles of rectangular shape with overall dimensions that vary from 6.0 × 14.5 × 12.7 to 6.0 × 15.7 × 19.9 Å3, whereas an odd number generates hexagon‐shaped assemblies with overall dimensions in the range 5.0 × 16.3 × 13.0 to 6.0 × 21.1 × 18.7 Å3. The computational analysis ruled out the possibility that monomeric structures had formed and indicated that for the creation of strain‐free mononuclear macrocyclic structures at least 14 methylene groups are required in the spacer.