bluuebunny/crossref_metadata_2025 huggingface dataset:
Psalm 118 (117 lxx) in Luke-Acts: Application of a 'New Exodus Motif'
Authors: Kwon Hyuk J.
Published: December 2009

This contribution explores the presence of Psalm 118 (117 LXX) in Luke-Acts. The Wirkungsgeschichte of Psalm 118 will be traced by means of a twofold approach: from a traditional-historical and a hermeneutical angle with regard to the reception history of Psalm 118. Firstly, in terms of a traditional-historical, otherwise known as a diachronic, approach, the background of Psalm 118 and evidence of the use and application of Psalm 118 in the tradition (namely in the ancient Jewish materials, such as the Dead Sea Scrolls, the Targums, and Rabbinics, and the New Testament books of Mark, Matthew, Luke, Acts, John, Romans, 2 Corinthians, Ephesians, 1 Peter, Hebrews, Revelation, as well as in terms of Church Fathers 1 Clement and Barnabas and the Apocryphon Thomas) will be discussed. Secondly, on the hermeneutical level, otherwise known as the synchronic approach, the function and interpretation of the quotations of Psalm 118 in its new context of Luke-Acts will be examined. In terms of the latter approach, attention will be paid to investigating a possible underlying �New Exodus Motif�.
The Neolithization of Northern Black Sea area in the context of climate changes
Authors: Kotova Nadezhda
Published: December 2009

The neolithisation of the Pontic steppe was a long process, with four stages which were associated with climate changes. It began c. 7500 calBC, with early animal husbandry in the western Azov Sea area. The beginning of the second stage was connected with an arid climate (7000–6900 calBC) and the origin of the Rakushechny Yar culture in the Lower Don region. The third stage (6500–6300 calBC) occurred during a humid period. Besides animal husbandry, the steppe population borrowed the first pottery from the Rakushechny Yar culture. The fourth phase (6300–6000 calBC) was connected with extreme aridity and the neolithisation of the modern forest-steppe and forest zones of Ukraine and Russia.
Tradition and innovation between the Mesolithic and early Neolithic in the Adige Valley (northeast Italy). New data from a functional analysis of trapezes from the Gaban rock-shelter
Authors: Cristiani Emanuela , Pedrotti Annaluisa , Gialanella Stefano
Published: December 2009

The Neolithisation of the Northern Italy is particularly interesting since archaeological data show dynamics of interaction between the last hunters and the early farmers of the region. In this paper the authors present the results of use-wear and residues analyses carried out on an assemblage of trapezes from one of the key-sites of the Neolithisation in the Adige Valley: Gaban rockshelter. The functional data have been compared and discussed with other strands of archaeological evidence available for the region.
Some thoughts on social versus cultural complexity
Authors: Cvekić Rastko
Published: December 2009

Socially complex hunter-gatherers are characterised by (1) inherited, permanent leadership and (2) sustained control over non-kin labour. Archaeologists have tended to infer social complexity through evidence of cultural complexity (i.e., artistic elaboration, composite tool technology, religion, etc). Complexity theory, however, indicates that patterns suggestive of social complexity can be produced through simple behavioural rules that do not necessitate social hierarchies. Therefore,evidence of cultural complexity cannot be used to infer social complexity in archaeological societies, nor should social complexity be emphasized in discussions of hunter-gatherer achievement or evolution of food production.
Lithics in Neolithic Northern Greece: territorial perspectives from an off-obsidian area
Authors: Kourtessi-Philippakis Georgia
Published: December 2009

C. Renfrew’s research in the Aegean at the beginning of the 1970’s and his hypothesis on the diffusion of obsidian from the island of Milos greatly influenced views of Greek Prehistory. Further lithic studies, especially in the Southern Aegean, have served to further confirmation the prevalence of obsidian in this area during the Neolithic. The aim of this paper is to draw attention to areas such as Northern Greece that are situated on the periphery of the Melian obsidian domain, where local materials occur in connection with imported ones from the North and South. With the aid of various examples from major Neolithic sites, we will discuss the question of procurement strategies in association with the reduction sequences of each material in use in this region, and outline trends of territorial organization among Neolithic farmers in the area.
Carbohydrate‐Oligonucleotide Conjugates
Authors: Pourceau Gwladys , Meyer Albert , Vasseur Jean‐Jacques , Morvan François
Published: December 2009

This unit describes a strategy for attaching two mannose and two galactose residues to an oligonucleotide. This conjugation can be performed at the 5′‐end of the oligonucleotide sequence, using modified phosphoramidites. First, the oligonucleotide scaffold is synthesized on solid support using a DNA synthesizer, with commercially available and modified phosphoramidites. After the first “click” reaction with a galactosylated azide derivative on solid support, the bromine atoms are replaced with azides and a second click reaction is performed with propargylated mannose either on solid support or in solution. Additionally, using a monoalkynated solid support, the conjugation with carbohydrate residues can be performed at the 3′‐end of the oligonucleotide according to a similar protocol. Curr. Protoc. Nucleic Acid Chem. 39:4.38.1‐4.38.25. © 2009 by John Wiley & Sons, Inc.
Chemical Modification of siRNA
Authors: Deleavey Glen F. , Watts Jonathan K. , Damha Masad J.
Published: December 2009

The ability to manipulate the RNA interference (RNAi) machinery to specifically silence the expression of target genes could be a powerful therapeutic strategy. Since the discovery that RNAi can be triggered in mammalian cells by short double‐stranded RNAs (small interfering RNA, siRNA), there has been a tremendous push by researchers, from academia to big pharma, to move siRNAs into clinical application. The challenges facing siRNA therapeutics are significant. The inherent properties of siRNAs (polyanionic, vulnerable to nuclease cleavage) make clinical application difficult due to poor cellular uptake and rapid clearance. Side effects of siRNAs have also proven to be a further complication. Fortunately, numerous chemical modification strategies have been identified that allow many of these obstacles to be overcome. This unit will present an overview of (1) the chemical modifications available to the nucleic acid chemist for modifying siRNAs, (2) the application of chemical modifications to address specific therapeutic obstacles, and (3) the factors that must be considered when assessing the activity of modified siRNAs. Curr. Protoc. Nucleic Acid Chem. 39:16.3.1‐16.3.22. © 2009 by John Wiley & Sons, Inc.
Bifunctional Acid–Base Ionic Liquid Organocatalysts with a Controlled Distance Between Acid and Base Sites
Authors: Boronat Mercedes , Climent Maria J. , Corma Avelino , Iborra Sara , Montón Raquel , Sabater Maria J.
Published: December 2009

Bifunctional acid–base ionic liquid organocatalysts with different distances between the two sites have been synthesised, and their activity for the Knoevenagel condensation has been tested. As has been found to be the case with enzymes, the distance between the acidic and basic sites determines the activity of the bifunctional organocatalyst, and at the optimal distance the reaction rate increases by two orders of magnitude with respect to the purely acidic or basic counterpart organocatalysts. The experimental results have been rationalised through the study of the reaction mechanism of the Knoevenagel condensation between malononitrile and benzaldehyde by means of DFT calculations. It has been found that it consists of two consecutive steps. First, deprotonation of malononitrile on the basic site to obtain a methylene carbanion intermediate takes place, and second, co‐adsorption and activation of benzaldehyde on the acid centre of this intermediate followed by the CC bond‐formation reaction. The calculations and the kinetic study indicate that there is an inversion of the rate‐controlling step when the distance between the acidic and the basic sites is modified, with a direct implication on the reaction rate.
Photochemical Reduction of Carbon Dioxide Catalyzed by a Ruthenium‐Substituted Polyoxometalate
Authors: Khenkin Alexander M. , Efremenko Irena , Weiner Lev , Martin Jan M. L. , Neumann Ronny
Published: December 2009

A polyoxometalate of the Keggin structure substituted with RuIII, 6Q5[RuIII(H2O)SiW11O39] in which 6Q=(C6H13)4N+, catalyzed the photoreduction of CO2 to CO with tertiary amines, preferentially Et3N, as reducing agents. A study of the coordination of CO2 to 6Q5[RuIII(H2O)SiW11O39] showed that 1) upon addition of CO2 the UV/Vis spectrum changed, 2) a rhombic signal was obtained in the EPR spectrum (gx=2.146, gy=2.100, and gz=1.935), and 3) the 13C NMR spectrum had a broadened peak of bound CO2 at 105.78 ppm (Δ1/2=122 Hz). It was concluded that CO2 coordinates to the RuIII active site in both the presence and absence of Et3N to yield 6Q5[RuIII(CO2)SiW11O39]. Electrochemical measurements showed the reduction of RuIII to RuII in 6Q5[RuIII(CO2)SiW11O39] at −0.31 V versus SCE, but no such reduction was observed for 6Q5[RuIII(H2O)SiW11O39]. DFT‐calculated geometries optimized at the M06/PC1//PBE/AUG‐PC1//PBE/PC1‐DF level of theory showed that CO2 is preferably coordinated in a side‐on manner to RuIII in the polyoxometalate through formation of a RuO bond, further stabilized by the interaction of the electrophilic carbon atom of CO2 to an oxygen atom of the polyoxometalate. The end‐on CO2 bonding to RuIII is energetically less favorable but CO2 is considerably bent, thus favoring nucleophilic attack at the carbon atom and thereby stabilizing the carbon sp2 hybridization state. Formation of a O2C–NMe3 zwitterion, in turn, causes bending of CO2 and enhances the carbon sp2 hybridization. The synergetic effect of these two interactions stabilizes both Ru–O and C–N interactions and probably determines the promotional effect of an amine on the activation of CO2 by [RuIII(H2O)SiW11O39]5−. Electronic structure analysis showed that the polyoxometalate takes part in the activation of both CO2 and Et3N. A mechanistic pathway for photoreduction of CO2 is suggested based on the experimental and computed results.
Mechanistic Investigation of the Dipolar [2+2] Cycloaddition–Cycloreversion Reaction between 4‐(N,N‐Dimethylamino)phenylacetylene and Arylated 1,1‐Dicyanovinyl Derivatives To Form Intramolecular Charge‐Transfer Chromophores
Authors: Wu Yi‐Lin , Jarowski Peter D. , Schweizer W. Bernd , Diederich François
Published: December 2009

The kinetics and mechanism of the formal [2+2] cycloaddition–cycloreversion reaction between 4‐(N,N‐dimethylamino)phenylacetylene (1) and para‐substituted benzylidenemalononitriles 2 b–2 l to form 2‐donor‐substituted 1,1‐dicyanobuta‐1,3‐dienes 3 b–3 l via the postulated dicyanocyclobutene intermediates 4 b–4 l have been studied experimentally by the method of initial rates and computationally at the unrestricted B3LYP/6‐31G(d) level. The transformations were found to follow bimolecular, second‐order kinetics, with ${{\rm{\Delta }}H_{{\rm{exp}}}^{ {\ne} } }$=13–18 kcal mol−1, ${{\rm{\Delta }}S_{{\rm{exp}}}^{ {\ne} } }$≈−30 cal K−1 mol−1, and ${{\rm{\Delta }}G_{{\rm{exp}}}^{ {\ne} } }$=22–27 kcal mol−1. These experimental activation parameters for the rate‐determining cycloaddition step are close to the computational values. The rate constants show a good linear free energy relationship (ρ=2.0) with the electronic character of the para‐substituents on the benzylidene moiety in dimethylformamide (DMF), which is indicative of a dipolar mechanism. Analysis of the computed structures and their corresponding solvation energies in acetonitrile suggests that the rate‐determining attack of the nucleophilic, terminal alkyne carbon onto the dicyanovinyl electrophile generates a transient zwitterion intermediate with the negative charge developing as a stabilized malononitrile carbanion. The computational analysis predicted that the cycloreversion of the postulated dicyanocyclobutene intermediate would become rate‐determining for 1,1‐dicyanoethene (2 m) as the electrophile. The dicyanocyclobutene 4 m could indeed be isolated as the key intermediate from the reaction between alkyne 1 and 2 m and characterized by X‐ray analysis. Facile first‐order cycloreversion occurred upon further heating, yielding as the sole product the 1,1‐dicyanobuta‐1,3‐diene 3 m.
Positive Homotropic Allosteric Receptors for Neutral Guests: Annulated Tetrathiafulvalene–Calix[4]pyrroles as Colorimetric Chemosensors for Nitroaromatic Explosives
Authors: Park Jung Su , Le Derf Franck , Bejger Christopher M. , Lynch Vincent M. , Sessler Jonathan L. , Nielsen Kent A. , Johnsen Carsten , Jeppesen Jan O.
Published: December 2009

The study of positive homotropic allosterism in supramolecular receptors is important for elucidating design strategies that can lead to increased sensitivity in various molecular recognition applications. In this work, the cooperative relationship between tetrathiafulvalene (TTF)‐calix[4]pyrroles and several nitroaromatic guests is examined. The design and synthesis of new annulated TTF‐calix[4]pyrrole receptors with the goal of rigidifying the system to accommodate better nitroaromatic guests is outlined. These new derivatives, which display significant improvement in terms of binding constants, also display a positive homotropic allosteric relationship, as borne out from the sigmoidal nature of the binding isotherms and analysis by using the Hill equation, Adair equation, and Scatchard plots. The host–guest complexes themselves have been characterized by single‐crystal X‐ray diffraction analyses and studied by means of UV‐spectroscopic titrations. Investigations into the electronic nature of the receptors were made by using cyclic voltammetry; this revealed that the binding efficiency was not strictly related to the redox potential of the receptor. On the other hand, this work serves to illustrate how cooperative effects may be used to enhance the recognition ability of TTF‐calix[4]pyrrole receptors. It has led to new allosteric systems that function as rudimentary colorimetric chemosensors for common nitroaromatic‐based explosives, and which are effective even in the presence of potentially interfering anions.
Belastbare Enzympräparate für die technische Biokatalyse
Authors: Ansorge‐Schumacher M. B. , Nieguth R. , Wiemann L. O. , Weißhaupt P. , Thum O. , Eckstein M.
Published: December 2009

Bei einer technischen Nutzung von Biokatalysatoren mit adsorptiv immobilisierten Enzymen sind die Desorptionsbeständigkeit der Enzyme und die mechanische Stabilität der Träger von besonderer Bedeutung. Die daraus resultierenden Limitierungen können durch eine Stabilisierung der Immobilisate mit Silicon weitgehend überwunden werden. Dies wurde anhand der Lipase B von C. antarctica (CALB), adsorbiert auf einem makroporösen Träger aus Polymethylmethacrylat, demonstriert. Im Zuge der experimentellen Evaluierung wurden sowohl der Einfluss verschiedener Siliconmengen, als auch unterschiedlicher Monomerkombinationen auf Trägermorphologie, katalytische Aktivität und mechanische Belastbarkeit untersucht. Dabei konnte eine deutliche Verminderung der Desorption des Enzyms vom Träger sowie eine Stabilisierung gegenüber mechanischem Stress, wie er in Rührwerksreaktoren auftritt, nachgewiesen werden.
Mikrobielle Umsetzung von β‐Phenylalanin mittels neuer Transaminasen
Authors: Brucher B. , Syldatk C. , Rudat J.
Published: December 2009

Bei der Untersuchung der Metabolisierung aromatischer β‐Aminosäuren wurden bei zahlreichen Bakterienstämmen eine stereoselektive Aufnahme sowie neuartige Transaminasen zur Verwertung dieser Verbindungen entdeckt. Racematspaltung mittels stereoselektiven Transports sowie Transaminierung von β‐Ketosäuren könnten neue Wege zur Gewinnung enantiomerenreiner β‐Aminosäuren darstellen. Gegenüber der Racematspaltung würde die Transaminierung eine wesentlich höhere Ausbeute des gewünschten Isomers ermöglichen.
Parallel heterogeneous CBIR system for efficient hyperspectral image retrieval using spectral mixture analysis
Authors: Plaza Antonio J. , Plaza Javier , Paz Abel
Published: December 2009

The purpose of content‐based image retrieval (CBIR) is to retrieve, from real data stored in a database, information that is relevant to a query. In remote sensing applications, the wealth of spectral information provided by latest‐generation (hyperspectral) instruments has quickly introduced the need for parallel CBIR systems able to effectively retrieve features of interest from ever‐growing data archives. To address this need, this paper develops a new parallel CBIR system that has been specifically designed to be run on heterogeneous networks of computers (HNOCs). These platforms have soon become a standard computing architecture in remote sensing missions due to the distributed nature of data repositories. The proposed heterogeneous system first extracts an image feature vector able to characterize image content with sub‐pixel precision using spectral mixture analysis concepts, and then uses the obtained feature as a search reference. The system is validated using a complex hyperspectral image database, and implemented on several networks of workstations and a Beowulf cluster at NASA's Goddard Space Flight Center. Our experimental results indicate that the proposed parallel system can efficiently retrieve hyperspectral images from complex image databases by efficiently adapting to the underlying parallel platform on which it is run, regardless of the heterogeneity in the compute nodes and communication links that form such parallel platform. Copyright © 2009 John Wiley & Sons, Ltd.
An inventory and update of jealousy‐evoking partner behaviours in modern society
Authors: Dijkstra Pieternel , Barelds Dick P. H. , Groothof Hinke A. K.
Published: December 2009

The goal of the present study was to identify the most important jealousy‐evoking partner behaviours and to examine the extent to which these behaviours evoke jealousy. Based on the literature, a questionnaire was constructed containing 42 jealousy‐evoking partner behaviours, including a partner's extra‐dyadic involvement with someone else by means of modern communication devices, such as the Internet. A second study examined the extent to which undergraduates and a community sample experienced jealousy in response to these partner behaviours. Results showed that explicit unfaithful behaviours evoked most feelings of jealousy, followed by a partner's emotional or romantic involvement with someone else by means of modern communication devices. In general, older individuals responded with less jealousy in response to a partner's unfaithful and suspicious behaviours. Clinical implications are discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Key Practitioner Message:

A partner's involvement with someone else by means of modern communication devices may evoke strong feelings of jealousy, in particular among women.

An individual's age affects the extent to which he or she experiences jealousy in response to specific extra‐dyadic partner behaviours.

In order to correctly diagnose and treat pathological jealousy, clinicians should pay attention to the extent to which partners (unintentionally) evoke and maintain feelings of jealousy.

Identifying partner behaviours that evoke most jealousy may help couples define the boundaries of their relationship.
Next‐generation antimalarial drugs: hybrid molecules as a new strategy in drug design
Authors: Muregi Francis W. , Ishih Akira
Published: December 2009

Malaria is a disease that affects nearly 40% of the global population, and chemotherapy remains the mainstay of its control strategy. The global malaria situation is increasingly being exacerbated by the emergence of drug resistance to most of the available antimalarials, necessitating search for novel drugs. A recent rational approach of antimalarial drug design characterized as “covalent bitherapy” involves linking two molecules with individual intrinsic activity into a single agent, thus packaging dual‐activity into a single hybrid molecule. Current research in this field seems to endorse hybrid molecules as the next‐generation antimalarial drugs. If the selective toxicity of hybrid prodrugs can be demonstrated in vivo with good bioavailability at the target site in the parasite, it would offer various advantages including dosage compliance, minimized toxicity, ability to design better drug combinations, and cheaper preclinical evaluation while achieving the ultimate object of delaying or circumventing the development of resistance. This review is focused on several hybrid molecules that have been developed, with particular emphasis on those deemed to have high potential for development for clinical use. Drug Dev Res 71: 20–32, 2010. © 2009 Wiley‐Liss, Inc.
Which drug is effective and safe for acute malaria in pregnancy? Reviewing the evidence
Authors: McGready Rose , Nosten François
Published: December 2009

During pregnancy, a woman living or travelling in a malaria endemic area is more at risk of contracting the disease and developing a severe infection and dying than a non‐pregnant woman. Despite this increased morbidity and mortality in pregnancy, there are almost no studies on which to base recommendations on the use of antimalarial drugs in this vulnerable group. This is because, paradoxically, the emphasis is often put on the safety of the unborn child rather than that of the infested mother. As a result of this neglect, tens of thousands of pregnant women (and their fetuses) are dying every year of a very preventable and treatable infection. In recent years, some trials have been conducted, especially in areas of high resistance in Plasmodium falciparum in South East Asia. The results show that quinine plus clindamycin is the treatment of choice in the first trimester, while artemisinin treatment should be used in the second and third trimesters in the treatment of uncomplicated malaria. For severe malaria, parenteral artesunate is the treatment of choice. However these studies have also shown that the pharmacokinetic properties of most antimalarials are altered during gestation and that the doses used in non‐pregnant adults are often not adapted to pregnancy. Urgent efforts are required to optimize the treatment of malaria in pregnancy. Drug Dev Res 71:56–68, 2010. © 2009 Wiley‐Liss, Inc.
Gaining time: early treatment of severe pediatric malaria in Tanzania
Authors: Gomes M.F. , Warsame M. , Nasemba N. , Singlovic J. , Kapinga A. , Mwankuyse S. , Mduma S. , Msabaha M.H. , Mulokosi F. , Shishira J. , Kitua A. , Mrango Z.
Published: December 2009

Early effective treatment prevents death or disability from malaria. In malaria‐endemic rural areas, pediatric patients who cannot take drugs orally and require injectable treatment have to be transported to the nearest facility that can give injectable malaria drugs. If time to reach the hospital is long, pre‐referral treatment and effective referral can play a major positive role. We compare the clinical course of illness and time taken to reach hospital in patients from Study 13, a randomized controlled study of pre‐referral rectal artesunate in which rapid referral was emphasized, with a comparator group of pediatric patients admitted at the same hospital in Tanzania whose parents' actions prior to admission at the hospital reflected routine behavior. The key difference was that parents of sick children from the intervention study rapidly transferred their children to the hospital following the advice they were given. Time gained by the referral study was 48 h and this difference was reflected in less severe symptoms at admission. Efforts to improve referral advice in the community can be a powerful complement to other malaria case management strategies. Drug Dev Res 71: 92–98, 2010. © 2009 Wiley‐Liss, Inc.
Conception of self‐construction production scheduling system
Authors: Xue Hai , Zhang Xuerui , Shimizu Yasuhiro , Fujimura Shigeru
Published: December 2009

With the high speed innovation of information technology, many production scheduling systems have been developed. However, a lot of customization according to individual production environment is required, and then a large investment for development and maintenance is indispensable. Therefore now the direction to construct scheduling systems should be changed. The final objective of this research aims at developing a system which is built by it extracting the scheduling technique automatically through the daily production scheduling work, so that an investment will be reduced. This extraction mechanism should be applied for various production processes for interoperability. Using the master information extracted by the system, production scheduling operators can be supported to accelerate the production scheduling work easily and accurately without any restriction of scheduling operations. By installing this extraction mechanism, it is easy to introduce a scheduling system without a lot of expense for customization. In this paper, first a model for expressing a scheduling problem is proposed. Then the guideline to extract the scheduling information and use the extracted information is shown and some applied functions are also proposed based on it. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 93(1): 19–29, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10188
Nickel‐Catalyzed Solvent‐Free Three‐Component Coupling of Aldehyde, Alkyne and Amine
Authors: Namitharan Kayambu , Pitchumani Kasi
Published: December 2009

A versatile three‐component coupling of aldehydes, alkynes and amines has been developed, catalyzed by Ni2+‐exchanged Y‐zeolite, which acts as an environmentally benign, recyclable, efficient and heterogeneous catalyst. This three‐component (A3) coupling (reported for the first time to proceed under nickel catalysis) is carried out under solvent‐free conditions, and the corresponding propargylamines are obtained in good to excellent yields.
Statistical inference for food webs with emphasis on ecological networks via Bayesian melding
Authors: Chiu Grace S. , Gould Joshua M.
Published: December 2009

Quantifying activities in a food web or ecological network, and related aspects of dependence, has largely been either descriptive or deterministic. Although schemes exist for assessing the reliability of such quantification, many are far from being statistical in nature. Statistical modeling approaches are explored, with a focus on the ecosystem aspects of a food web. By employing Bayesian melding, we provide a new statistical inferential approach for understanding ecological networks in the context of mass balance. Our approach embodies the traditional deterministic views on network relations, yet it is developed on the basis of proper statistical inference that allows the estimation of physical quantities and probabilistic assessment of the estimation. We describe our approach, and illustrate it with a mass balance dataset. The practical advantage of our approach is a more realistic understanding of the network by incorporating natural measurement variability into deterministic beliefs about the relationships among measurements. The resulting inference thus forms a more honest representation of the true state of nature, and provides a formal assessment of balance before data are passed on to later stages of an ecological network analysis (ENA). We also demonstrate that general Bayesian inference for ENA can yield new ecological insight that may not be available through standard classical inference. Copyright © 2009 John Wiley & Sons, Ltd.
Assessing the value of Hermite densities for predictive distributions
Authors: Mauleón Ignacio
Published: December 2009

The empirical behaviour of two Hermitian densities—the Edgeworth asymptotic expansion, and the Gallant and Nychka (1987) squared transformation—are assessed and compared to Hansen's (1994) asymmetric Studentt. The comparison focuses on VaR measurements and overall probability fits. In and out of sample, Berkowitz's (2001) extended procedures are also implemented. Results are moderately favourable to the Hermitians, supporting the semi‐nonparametric interpretation, and multivariate developments. Copyright © 2009 John Wiley & Sons, Ltd.
Lack of HLA class II antigen expression in microsatellite unstable colorectal carcinomas is caused by mutations in HLA class II regulatory genes
Authors: Michel Sara , Linnebacher Michael , Alcaniz Joshua , Voss Maike , Wagner Rudolf , Dippold Wolfgang , Becker Christina , von Knebel Doeberitz Magnus , Ferrone Soldano , Kloor Matthias
Published: December 2009

Colorectal cancers (CRCs) develop on the basis of a deficient DNA mismatch repair (MMR) system in about 15% of cases. MMR‐deficient CRC lesions show high‐level microsatellite instability (MSI‐H) and accumulate numerous mutations located at coding microsatellite loci that lead to the generation of immunogenic neopeptides. Consequently, the host's antitumoral immune response is of high importance for the course of the disease in MSI‐H CRC patients. Accordingly, immune evasion mediated by impairment of HLA class I antigen presentation is frequently observed in these cancers. In this study, we aimed at a systematic analysis of alterations affecting HLA class II antigen expression in MSI‐H CRC. HLA class II antigens are expressed by only two‐thirds of MSI‐H CRCs. The mechanisms underlying the lack of HLA class II antigens in a subset of MSI‐H CRCs remain unknown. We here screened HLA class II regulatory genes for the presence of coding microsatellites and identified mutations of the essential regulator genes RFX5 in 9 (26.9%) out of 34 and CIITA in 1 (2.9%) out of 34 MSI‐H CRCs. RFX5 mutations were related to lack of or faint HLA class II antigen expression (p = 0.006, Fisher's exact test). Transfection with wild‐type RFX5 was sufficient to restore interferon gamma‐inducible HLA class II antigen expression in the RFX5‐mutant cell line HDC108. We conclude that somatic mutations of the RFX5 gene represent a novel mechanism of loss of HLA class II antigen expression in tumor cells, potentially contributing to immune evasion in MSI‐H CRCs.
A novel role of gap junction connexin46 protein to protect breast tumors from hypoxia
Authors: Banerjee Debarshi , Gakhar Gunjan , Madgwick Dan , Hurt Amy , Takemoto Dolores , Nguyen Thu Annelise
Published: December 2009

Connexin proteins are the principle structural components of the gap junctions. Colocalization and tissue‐specific expression of diverse connexin molecules are reported to occur in a variety of organs. Impairment of gap junctional intercellular communication, caused by mutations, gain of function or loss of function of connexins, is involved in a number of diseases including the development of cancer. Here we show that human breast cancer cells, MCF‐7 and breast tumor tissues express a novel gap junction protein, connexin46 (Cx46) and it plays a critical role in hypoxia. Previous studies have shown that connexin46 is predominantly expressed in lens and our studies find that Cx46 protects human lens epithelial cells from hypoxia induced death. Interestingly, we find that Cx46 is upregulated in MCF‐7 breast cancer cells and human breast cancer tumors. Downregulation of Cx46 by siRNA promotes 40% MCF‐7 cell death at 24 hr under hypoxic conditions. Furthermore, direct injection of anti‐Cx46 siRNA into xenograft tumors prevents tumor growth in nude mice. This finding will provide an exciting new direction for drug development for breast cancer treatment and suggests that both normal hypoxic tissue (lens) and adaptive hypoxic tissue (breast tumor) utilize the same protein, Cx46, as a protective strategy from hypoxia.
E2F‐1 RNomics is critical for reprogramming of cancer cells to quiescent state
Authors: Mehrotra Aanchal , Joshi Kusum , Kaul Deepak
Published: December 2009

The discovery of cooperativity between pRB and E2F greatly prompted various investigators to find how E2F biology contributes to oncogenesis. Although E2F family of transcription factors have been linked to proliferation, apoptosis and differentiation, yet no heed has been paid to understand the role of E2F biology in cellular quiescence. To understand the functional RNomics (regulation of gene transcription through RNA interference) of E2F‐1 gene, 2 cancer cell lines, such as Jurkat exhibiting E2F‐1 gene overamplification and Hela‐229 exhibiting intrinsic downregulation of E2F‐1 gene expression, were used in our study. E2F‐1 gene knockdown via siRNA within Jurkat cells resulted in upregulation of genes characteristic of quiescence both translationally and transcriptionally, which was accompanied by downregulation of genes at both translational and transcriptional level involved in cell cycle progression and apoptosis. This genomic phenomenon also translated into ultrastructural and phenotypic features typical of quiescent state. These observed results in Jurkat cells were simulated by upregulation of E2F‐1 gene in Hela‐229 cells through the downregulation of miR 17‐5p. This E2F‐1‐regulated pathway explained as to how Jurkat cells entered exclusively into quiescent state when E2F‐1 was downregulated in these cells and how Hela‐229 cells proliferate vigorously when E2F‐1 was upregulated in such cells. Here, we propose a gene‐regulatory pathway which the cell might be using in its entry into either quiescent or proliferative states. Furthermore, this pathway may be useful in designing strategies for the treatment of cancer in general and acute lymphoblastic leukemia in particular.
Antitumorigenic effects of a mutant of the heparin affin regulatory peptide on the U87 MG glioblastoma cell line
Authors: Santos Célia Dos , Karaky Racha , Renoir Dominique , Hamma‐Kourbali Yamina , Albanese Patricia , Gobbo Emilie , Griscelli Frank , Opolon Paule , Dalle Sophie , Perricaudet Michel , Courty José , Delbé Jean
Published: December 2009

Glioblastoma is the most common primary brain tumor in human adults. Since existing treatments are not effective enough, novel therapeutic targets must be sought. The heparin‐binding growth factor, heparin affin regulatory peptide (HARP), also known as pleiotrophin (PTN), could potentially represent such a target. We have previously shown that a mutant protein, HARPΔ111–136, which lacks HARP's C‐terminal 26 amino acids, acts as a dominant negative HARP effector by heterodimerizing with the wild‐type growth factor. The aim of our study was to evaluate the potential inhibitory activity of HARPΔ111–136 on the U87 MG human glioblastoma cell line. By overexpressing the truncated form of HARP in stably established clones of U87 MG cells, we observed an inhibition of proliferation under both anchorage‐dependent and anchorage‐independent conditions. We confirmed these results in an in vivo subcutaneous tumor xenograft model. In addition, we found that HARPΔ111–136 inhibited cell proliferation in a paracrine manner. Analysis of key cellular pathways revealed a decrease of cell adhesion in U87 MG cells that overexpressed the mutant protein, which could explain this inhibitory effect. A replication‐defective adenovirus model that encoded HARPΔ111–136 supported a putative antiproliferative role for the truncated protein in vitro and in vivo. Interestingly, HARPΔ111–136 was also able to abolish angiogenic activity in HUVEC proliferation and in a Matrigel plug assay. These results demonstrate that considering its antiproliferative and angiostatic effects, HARPΔ111–136 could be of great interest when used in conjunction with standard treatments.
Anti‐inflammatory M2 type macrophages characterize metastasized and tyrosine kinase inhibitor‐treated gastrointestinal stromal tumors
Authors: van Dongen Minka , Savage Nigel D.L. , Jordanova Ekaterina S. , Briaire‐de Bruijn Inge H. , Walburg Kimberley V. , Ottenhoff Tom H.M. , Hogendoorn Pancras C.W. , van der Burg Sjoerd H. , Gelderblom Hans , van Hall Thorbald
Published: December 2009

We have made a detailed inventory of the immune infiltrate of gastrointestinal stromal tumors (GISTs), which originate from mesenchymal cells in the intestinal tract. These sarcomas are heavily infiltrated with macrophages and T cells, while immune cells of other lineages were much less abundant. Dissecting the functional subtypes of T cells with multicolor fluorescent microscopy revealed substantial populations of cytotoxic T cells, helper T cells and FoxP3+ regulatory T cells. The balance of cytotoxic T cells and FoxP3+ T cells was toward immune suppression. Analysis of the macrophage population also showed a dominance of anti‐inflammatory cells, as the M2 type scavenger receptor CD163 was abundantly present. Other subsets of macrophages (CD14+CD163−) were occasionally detected. M2 type CD163+ macrophages were associated with the number of infiltrating FoxP3+ regulatory T cells and twice as many macrophages were found in metastatic GIST compared to primary lesions. Most metastatic GISTs had been treated with the tyrosine kinase inhibitors imatinib and sunitinib, but the high macrophage infiltrate was not related to this treatment. However, imatinib and sunitinib did induce secretion of anti‐inflammatory IL‐10 in macrophage cultures, indicating that treatment with these inhibitors might contribute to an immune suppressive microenvironment in GIST. Overall, our data reveal a picture of GIST as an active site of tumor‐immune interaction in which suppressive mechanisms overrule potential antitumor responses. Tyrosine kinase inhibitors might promote this negative balance.
Endomyocardial biopsy derived adherent proliferating cells—A potential cell source for cardiac tissue engineering
Authors: Haag Marion , Van Linthout Sophie , Schröder Sebastian E.A. , Freymann Undine , Ringe Jochen , Tschöpe Carsten , Sittinger Michael
Published: December 2009

Heart diseases are a leading cause of morbidity and mortality. Cardiac stem cells (CSC) are considered as candidates for cardiac‐directed cell therapies. However, clinical translation is hampered since their isolation and expansion is complex. We describe a population of human cardiac derived adherent proliferating (CAP) cells that can be reliably and efficiently isolated and expanded from endomyocardial biopsies (0.1 cm3). Growth kinetics revealed a mean cell doubling time of 49.9 h and a high number of 2.54 × 107 cells in passage 3. Microarray analysis directed at investigating the gene expression profile of human CAP cells demonstrated the absence of the hematopoietic cell markers CD34 and CD45, and of CD90, which is expressed on mesenchymal stem cells (MSC) and fibroblasts. These data were confirmed by flow cytometry analysis. CAP cells could not be differentiated into adipocytes, osteoblasts, chondrocytes, or myoblasts, demonstrating the absence of multilineage potential. Moreover, despite the expression of heart muscle markers like α‐sarcomeric actin and cardiac myosin, CAP cells cannot be differentiated into cardiomyocytes. Regarding functionality, CAP cells were especially positive for many genes involved in angiogenesis like angiopoietin‐1, VEGF, KDR, and neuropilins. Globally, principal component and hierarchical clustering analysis and comparison with microarray data from many undifferentiated and differentiated reference cell types, revealed a unique identity of CAP cells. In conclusion, we have identified a unique cardiac tissue derived cell type that can be isolated and expanded from endomyocardial biopsies and which presents a potential cell source for cardiac repair. Results indicate that these cells rather support angiogenesis than cardiomyocyte differentiation. J. Cell. Biochem. 109: 564–575, 2010. © 2009 Wiley‐Liss, Inc.
A single deletion at position 134, 135, or 136 in the beta 7–beta 8 loop of the p51 subunit of HIV‐1 RT disrupts the formation of heterodimeric enzyme
Authors: Upadhyay Alok , Pandey Nootan , Mishra Chaturbhuj A. , Talele Tanaji T. , Pandey Virendra N.
Published: December 2009

The human immunodeficiency virus type 1 reverse transcriptase (HIV‐1 RT) is a heterodimeric enzyme composed of p66 and p51 subunits. Earlier, we showed that the β7–β8 loop of p51 is crucial for polymerase activity of HIV‐1 RT as either deletion or Ala substitution of amino acids in the β7–β8 loop spanning residues 136‐139 in the p51 subunit impaired dimerization and, in turn, polymerase function of the enzyme (Pandey et al. 2001 Biochemistry 40: 9505–9512). In the present study, we generated subunit‐specific single‐deletion mutants at positions 134, 135, 136, or 137 and examined their effects on the heterodimerization, binary complex formation, and polymerase functions of the enzyme. We found that among these four residues, Ser134, Ile135, and Asn136 in the β7–β8 loop of the p51 subunit are crucial residues for dimerization and polymerase function of the enzyme, but have no impact when specifically deleted from the p66 subunit. These results demonstrate the β7–β8 loop of the p51 subunit in the formation of stable, functional heterodimeric enzyme which could be an attractive target for anti‐HIV‐1 drug development. J. Cell. Biochem. 109: 598–605, 2010. © 2009 Wiley‐Liss, Inc.
The ontogeny of Pseudis platensis (Anura, Hylidae): Heterochrony and the effects of larval development on postmetamorphic life
Authors: Fabrezi Marissa , Quinzio Silvia I. , Goldberg Javier
Published: December 2009

Recent studies have described the giant tadpole, delayed metamorphic transformations, and absence of postmetamorphic growth of the skeleton of Pseudis Platensis. These features address questions about derived patterns of life cycles and the role of the heterochrony during the metamorphosis in anurans. Using anatomical methods, we provide new data on the development of reproductive, digestive and integument systems, and age inference obtained from ontogenetic series of Pseudis platensis. Our results indicate that at the end of metamorphosis, the adult skin is completely differentiated, including the calcified dermal layer; the testis has seminiferous tubules with spermatogonia, spermatocytes, and spermatids; ovarian sacs present previtellogenic ova; and the adult digestive tract is fully formed. The froglets differ from adults only in being unable to reproduce. The entire life cycle of P. platensis can occur in 4 years. In the first year, larval development, growth to adult size, and gonad differentiation are completed. Long larval development rather than size of the tadpoles seems to be involved in the absence of juvenile stages. J. Morphol., 2010. © 2009 Wiley‐Liss, Inc.
Modulation of vocal fold scar fibroblasts by adipose‐derived stem/stromal cells
Authors: Kumai Yoshihiko , Kobler James B. , Park Hyoungshin , Galindo Marilyn , Herrera Victoria L.M. , Zeitels Steven M.
Published: December 2009

Objectives/Hypothesis:

To explore whether adipose‐derived stem/stromal cells (ASCs) have therapeutic potential for treating scarred superficial lamina propria through the effects of secreted hepatocyte growth factor (HGF) on scar fibroblasts.

Study Design:

In vitro study using coculture system.

Methods:

Scar fibroblasts (SFs) were isolated from ferret vocal folds electrocauterized 2 weeks previously. ASCs were isolated from ferret lipoaspirated subcutaneous abdominal fat. For coculture experiments, the two cell types were combined in Transwell plates for 6 days, followed by 1 or 3 days of monoculture after removing the upper chamber. Assays were then performed on cells and media from the bottom chamber. We measured: 1) the production of hyaluronic acid (HA), collagen and HGF via enzyme‐linked immunosorbent assays, 2) the expression of α‐smooth muscle actin (α‐SMA), 3) cell proliferation, and 4) apoptosis of SFs (2, 3, and 4 via flow cytometry). Other experiments examined the effects of HGF on SFs and the effects of HGF neutralization in the coculture system.

Results:

Coculture led to significant decreases in SF collagen production (P < .05), cell proliferation (P < .05), and α‐SMA expression (P < .05), whereas HA production increased (P < .05). Coculture also increased HGF secretion from ASCs (P < .05). Neutralization of HGF abolished the inhibitory effects of ASCs on SF collagen synthesis (P < .05).

Conclusions:

ASCs influence SFs to adopt a less fibrotic profile. It appears that HGF is at least one of the soluble factors responsible for this effect. Implanted ASCs could potentially ameliorate vocal fold scar by acting as long‐term, intrinsic sources of HGF. Laryngoscope, 2010
Impact of thyroidectomy without laryngeal nerve injury on vocal quality characteristics: An objective multiparameter approach
Authors: Van Lierde Kristiane , D'haeseleer Evelien , Wuyts Floris L. , Baudonck Nele , Bernaert Lut , Vermeersch Hubert
Published: December 2009

Objectives/Hypothesis:

The main purpose of this study was to determine the impact of thyroidectomy on the subjective and objective vocal quality using the Dysphonia Severity Index. It was hypothesized that objective measures of vocal function and other vocal characteristics would change (temporarily or permanently) from the presurgical to the postsurgical conditions, even with the entire preservation of the laryngeal nerve, due to the surgical approach and other influencing factors.

Study Design:

Prospective study in which 44 subjects were studied before (1 week) and three times post‐thyroidectomy.

Methods:

Subjective (auditory perceptual evaluation and videolaryngostroboscopy) and objective (aerodynamic, vocal range, acoustic, and Dysphonia Severity Index measurements) assessment techniques were used.

Results:

Paired samples t test indicated a significant decrease of the highest frequency, the highest intensity, the fundamental frequency, and the Dysphonia Severity Index in the first postoperative condition. When a repeated measures analysis of variance was performed with the pre‐ and all the postoperative moments of evaluation taken into account, no significant difference was noted for any of the objective voice characteristics.

Conclusions:

After thyroidectomy subjects had a normal perceptual and objective vocal quality corresponding with a Dysphonia Severity Index of 66%, and there is no permanent change of the vocal performance. Moreover, there is no psychosocial handicapping effect of the vocal quality, but immediately post‐thyroidectomy there are more vocal complaints. To what extent thyroidectomy causes (temporary or permanent) alterations of the singing voice in elite vocal performers is subject to further research. Laryngoscope, 2010
Green's function expansion for exponentially graded elasticity
Authors: Sallah Omar M. , Gray L. J. , Amer M. A. , Matbuly M. S.
Published: December 2009

New computational forms are derived for Green's function of an exponentially graded elastic material in three dimensions. By suitably expanding a term in the defining inverse Fourier integral, the displacement tensor can be written as a relatively simple analytic term, plus a single double integral that must be evaluated numerically. The integration is over a fixed finite domain, the integrand involves only elementary functions, and only low‐order Gauss quadrature is required for an accurate answer. Moreover, it is expected that this approach will allow a far simpler procedure for obtaining the first and second‐order derivatives needed in a boundary integral analysis. The new Green's function expressions have been tested by comparing with results from an earlier algorithm. Copyright © 2009 John Wiley & Sons, Ltd.