bluuebunny/crossref_metadata_2025 huggingface dataset:
Copper utilization in low fat diets
Authors: Aguirre M. , Navarro María P.
Published: May 2010

The objective of this study was to investigate both the dietary copper utilization and the body copper content in rats fed either low fat diets (2%) or normal fat diets (8%) containing olive oil, sunflower oil and palm oil (olein fraction), by two different balance techniques.
Seven groups of Wistar rats were used. One group was killed on the first experimental day being utilized as control of initial body copper content. Six groups of rats were fed, over 15 days, semipurified diets varying only in the fat level, three of them containing 8% of fat, and the other three 2%. The overall copper balance was studied by calculating differences between the initial and final body copper content. During the last week, another copper balance was carried out by monitoring intake and faecal copper excretion. Body mass, and liver, spleen, skin, erythrocytes and serum copper contents were also examined.
The copper utilization was lower in 2% fat rats, this was caused by food intake decrease but also by the lower copper bioavailability in 2% fat diets. The corporal, liver and spleen copper contents were reduced, and liver, skin and serum copper concentrations also decreased in the rats fed on 2% fat diets.
Palm olein (8%) versus olive and sunflower oil produced a lower efficiency of copper absorption.
Essential Role for TLR9 in Prime but Not Prime-Boost Plasmid DNA Vaccination To Activate Dendritic Cells and Protect from Lethal Viral Infection
Authors: Rottembourg Diane , Filippi Christophe M. , Bresson Damien , Ehrhardt Katrin , Estes Elizabeth A. , Oldham Janine E. , von Herrath Matthias G.
Published: May 2010

One of the requirements for efficient vaccination against infection is to achieve the best combination of an adequate adjuvant with the antigenic information to deliver. Although plasmid DNA is a promising tool bearing the unique potential to activate humoral and cellular immunity, an actual challenge is to increase plasmid immunogenicity in human vaccination protocols in which efficacy has proven rather limited. Previous work showed that the bacterial DNA backbone of the plasmid has potent adjuvant properties because it contains CpG motifs that are particular activating nucleotidic sequences. Among TLRs, which are key sensors of microbial products, TLR9 can detect CpG motifs and confer activation of APCs, such as dendritic cells. However, whether the immunogenic properties of plasmid DNA involve TLR9 signaling has not been clearly established. In the current study, we demonstrate that TLR9 determines the effectiveness of vaccination against lethal lymphocytic choriomeningitis virus infection using plasmid DNA in a prime, but not prime-boost, vaccination regimen. Furthermore, we provide evidence that the presence of TLR9 in dendritic cells is necessary for effective and functional priming of virus-specific CD8+ T cells upon plasmid exposure in vitro or single-dose vaccination in vivo. Therefore, at single or low vaccine doses that are often used in human-vaccination protocols, CpG/TLR9 interactions participate in the immunogenicity of plasmid DNA. These results suggest that the TLR9 signaling pathway is involved in the efficacy of plasmid vaccination; therefore, it should remain a focus in the development or amelioration of vaccines to treat infections in humans.
Conditional Superagonist CTL Ligands for the Promotion of Tumor-Specific CTL Responses
Authors: Abdul-Alim C. Siddiq , Li Yongqing , Yee Cassian
Published: May 2010

Although it has been demonstrated that CTLs can be raised against tumor-associated self-antigens, achieving consistent and effective clinical responses has proven challenging. Superagonist altered peptide ligands (APLs) can often elicit potent antitumor CTL responses where the native tumor-associated epitope fails. Current methods have identified a limited number of superagonist APLs, including the prototypic 27L mutant of MART-1. However, more comprehensive screening strategies would be desirable. In this study, we use a novel genetic screen, involving recombinant technology and class I Ag cross-presentation, to search for supraoptimal superagonists of the 27L MART-1 mutant by surveying the effectiveness of virtually every single amino acid substitution mutant of 27L to activate human Ag-specific CTL clones recognizing the wild-type MART-126–35 epitope. We identify three novel mutant epitopes with superagonist properties that are functionally superior to 27L; however, the ability of a given analogue to act as superagonist varies among patients and suggests that a given superagonist APL may be ideally suited to different patients. These findings endorse the use of comprehensive methods to establish panels of potential superagonist APLs to individualize tumor peptide vaccines among patients.
F1-Adenosine Triphosphatase Displays Properties Characteristic of an Antigen Presentation Molecule for Vγ9Vδ2 T Cells
Authors: Mookerjee-Basu Jayati , Vantourout Pierre , Martinez Laurent O. , Perret Bertrand , Collet Xavier , Périgaud Christian , Peyrottes Suzanne , Champagne Eric
Published: May 2010

Human Vγ9Vδ2 T lymphocytes are activated by phosphoantigens provided exogenously or produced by tumors and infected cells. Activation requires a contact between Vγ9Vδ2 cells and neighboring cells. We previously reported a role for cell surface F1-adenosine triphosphatase (ATPase) in T cell activation by tumors and specific interactions between Vγ9Vδ2 TCRs and purified F1-ATPase. 721.221 cells do not express surface F1-ATPase and do not support phosphoantigen responses unless they are rendered apoptotic by high doses of zoledronate, a treatment that promotes F1-expression as well as endogenous phosphoantigen production. By monitoring calcium flux in single cells, we show in this study that contact of T cells with F1-ATPase on polystyrene beads can partially replace the cell-cell contact stimulus during phosphoantigen responses. Triphosphoric acid 1-adenosin-5′-yl ester 3-(3-methylbut-3-enyl) ester, an adenylated derivative of isopentenyl pyrophosphate, can stably bind to F1-ATPase–coated beads and promotes TCR aggregation, lymphokine secretion, and activation of the cytolytic process provided that nucleotide pyrophosphatase activity is present. It also acts as an allosteric activator of F1-ATPase. In the absence of Vγ9Vδ2 cells, triphosphoric acid 1-adenosin-5′-yl ester 3-(3-methylbut-3-enyl) ester immobilized on F1-ATPase is protected from nucleotide pyrophosphatase activity, as is the antigenic activity of stimulatory target cells. Our experiments support the notion that Vγ9Vδ2 T cells are dedicated to the recognition of phosphoantigens on cell membranes in the form of nucleotide derivatives that can bind to F1-ATPase acting as a presentation molecule.
Blockade of CCL1 Inhibits T Regulatory Cell Suppressive Function Enhancing Tumor Immunity without Affecting T Effector Responses
Authors: Hoelzinger Dominique B. , Smith Shannon E. , Mirza Noweeda , Dominguez Ana Lucia , Manrique Soraya Zorro , Lustgarten Joseph
Published: May 2010

Intratumoral accumulation of T regulatory cells (Tregs) creates an immunosuppressive environment that reduces the efficacy of antitumor immunotherapy. The immunosuppressive milieu within tumors is largely brought about by the presence of Tregs, which maintain self-tolerance by directly inhibiting T cells, NK cells, and dendritic cells. Depletion of Tregs enhances antitumor immune responses; however, current depletion therapies also affect the function of CD4 and CD8 T effector cells. Previous studies from our laboratory indicate that intratumoral delivery of CpG-ODN strongly reduces the levels of Tregs within the tumor, which is mainly mediated by IL-6. Because IL-6 promotes growth of some human cancers, alternate pathways to inactivate Tregs were sought through microarray analysis, resulting in gene candidates that can be exploited to modulate the function of Tregs. Analysis of these candidates indicates that neutralization of chemokine (C-C motif) ligand 1 (CCL1) prevented de novo conversion and suppressive function of Tregs without affecting the function of T effector cells. The combination of CpG-ODN and anti-CCL1 treatments induced complete rejection of tumors in BALB-neuT tolerant mice, and result in the generation of long-term protective memory responses. Tumor rejection correlated with changes in the lymphocyte composition within the tumor; we observed decreased Treg numbers and a concomitant accumulation of tumoricidal cells such as CD8+NKG2D+ and NK cells. These studies demonstrate that neutralization of CCL1 can be used as an adjuvant to antitumor immunotherapy, as a means of reversing the immunosuppressive function of Tregs without compromising T cell effector function.
TLR2 Agonists Enhance CD8+Foxp3+ Regulatory T Cells and Suppress Th2 Immune Responses during Allergen Immunotherapy
Authors: Tsai Yi-Giien , Yang Kuender D. , Niu Dau-Ming , Chien Jien-Wen , Lin Ching-Yuang
Published: May 2010

Pam3CSK4, a synthetic TLR2 ligand, has been shown to expand CD4+ regulatory T cells (Treg cells). Less is known about the function of CD8+ Treg cells than about the function of CD4+ Treg cells generated during allergen-specific immunotherapy (IT). This study investigated whether Dermatophagoides pteronyssinus-specific IT could expand the CD8+CD25+Foxp3+ Treg population and whether Pam3CSK4 could enhance the Treg population. PBMCs were isolated from healthy control subjects and from mite-sensitive asthmatic patients during IT at three specific times: before IT and 6 mo and 1 y after the maximum-tolerated dose. This study was performed without a placebo-controlled group. D. pteronyssinus-specific IT induced a significant increase in CD8+Foxp3+ Treg cells expressing intracellular IL-10 and granzyme B. Costimulation of PBMCs with Pam3CSK4 and D. pteronyssinus 2 expanded the CD8+CD25+Foxp3+ Treg population and inhibited D. pteronyssinus 2-induced IL-4 production. Pam3CSK4-treated CD8+CD25+ Treg cells directly suppressed CD4+ T cell proliferation by cell-contact inhibition. TUNEL revealed that CD8+CD25+ Treg cells, but not CD4+CD25+ Treg cells, directly induced CD4+CD45ROhi+ apoptosis. Our results provide direct evidence that Pam3CSK4 induces an immunomodulatory effect by inducing CD8+ Treg cells; therefore, it may be a good adjuvant for the treatment of mite allergies.
Placental Vascular Obstructive Lesions: Risk Factor for Developing Necrotizing Enterocolitis
Authors: Dix Laure , Roth-Kleiner Matthias , Osterheld Maria-Chiara
Published: May 2010

Necrotizing enterocolitis (NEC) is a severe neonatal disease affecting particularly preterm infants. Its exact pathogenesis still remains unknown. In this study, we have compared the prevalence of vascular obstructive lesions in placentae of premature newborns which developed NEC and of a control group. We further compared separately the findings of placentae of infants of less than 30 weeks of gestation, the age group in which NEC occurs most frequently. We found signs of fetal vascular obstructive lesions in 65% of the placentae of preterm patients developing NEC, compared to only 17% of the placentae of preterm patients in the control group. In the age groups below 30 weeks of gestation, 58.5% of placentae of later NEC patients presented such lesions compared to 24.5% in the control group. The significant difference between NEC and control group suggests a strong association between fetal vascular obstructive lesions and NEC. Therefore, we propose that fetal vascular obstructive lesions might be considered as a risk factor for the development of NEC in premature infants.
Rapid evolution of phenoloxidase expression, a component of innate immune function, in a natural population of Daphnia magna
Authors: Pauwels Kevin , De Meester Luc , Put Stéphanie , Decaestecker Ellen , Decaestecker Ellen , Stoks Robby
Published: May 2010

We show rapid microevolution of one component of invertebrate innate immunity, phenoloxidase activity, in a natural population of the water flea Daphnia magna. In Daphnia hatched out of different depths of a sediment core, levels of Daphnia phenoloxidase activity showed genetic variation and increased significantly in less than a decade. We discuss this increase in Daphnia immunity over time in the light of coinciding changes in predator and parasite environment. Together with earlier‐found microevolutionary responses in stress protein expression of this Daphnia population, we find simultaneous changes of different defense systems in response towards multiple enemies.
Seasonal differences in the evolution of damped basin‐scale internal waves in a shallow stratified lake
Authors: Shimizu Kenji , Imberger Jörg
Published: May 2010

The evolution of damped basin‐scale internal waves was investigated using a modal analysis for layer‐stratified rotating lakes. A simple model for homogeneous oscillatory boundary layers was incorporated into the modal analysis to predict damping rates of individual internal‐wave modes, enabling the prediction of their evolution under wind forcing and bottom friction. Application of the method to Lake Kinneret indicated a different dynamic balance in summer and spring, despite the continuous presence of large amplitude internal waves in the two seasons. In summer, strong diurnal winds continuously excited the dominant Kelvin waves, but the relatively strong damping (e‐folding damping times ∼ 3 d) suppressed their amplitudes. In spring, wind forcing was again strong, but intermittent, and it was weaker damping (e‐folding damping times ∼ 10 d) that allowed the dominant Poincareé waves to persist until the next wind event. The significant difference in the damping times was due to the difference in the periods and the structure of the internal waves as well as the bottom boundary‐layer thickness, which limited the Ekman transport and energy dissipation within the boundary layer.
Postal Voting and Voter Turnout in Local Elections: Lessons from New Zealand and Australia
Authors: Zvulun Jacky Yaakov
Published: May 2010

The relationship between postal voting and voter turnout in local elections needs to be investigated in the context of whether postal voting helps increase voter turnout in twenty-first century local elections. This assists to uplift the discourse about New Zealand and Australia local elections and its voter turnout. This article explores the method of postal voting history by looking at these two countries and analysing the method of political participation at the local level. It argues that postal voting no longer increases or decreases voter turnout in these countries.

KEYWORDS: • postal voting • voter turnout • local elections • participation • New Zealand
Local Political Leadership in Urban Governance and Public Administration Modernisation: The Role of the Mayor and Councillors in a Spanish Municipality (1979-2007)
Authors: Alonso Ángel Iglesias , Mandeta Manuel Villoria
Published: May 2010

Implementing urban governance strategies to improve local democracy and to regulate local economic growth is an important determinant of effective local administrative change and performance. The underlying hypothesis adopted here is the assumption that the adoption of urban governance processes requires political leadership. It inevitably results in the introduction of innovations within the administrative apparatus in order to improve its performance. Indeed, understanding the interaction between these three aspects (political leadership, urban governance, and administrative modernisation) is of fundamental importance for the effectiveness of most, if not all, policy interventions directed at the introduction of democratic innovations and public administration modernisation initiatives in local governments. To bring out the importance of those interactions, case study1 research is used.

KEYWORDS: • local government • urban governance • administrative modernisation • public policy • political leadership • Spain
Optical properties of different aerosol types: seven years of combined Raman-elastic backscatter lidar measurements in Thessaloniki, Greece
Authors: Giannakaki E. , Balis D. S. , Amiridis V. , Zerefos C.
Published: May 2010

Abstract. We present our combined Raman/elastic backscatter lidar observations which were carried out at the EARLINET station of Thessaloniki, Greece, during the period 2001–2007. The largest optical depths are observed for Saharan dust and smoke aerosol particles. For local and continental polluted aerosols the measurements indicate high aerosol loads. However, measurements associated with the local path indicate enhanced aerosol load within the Planetary Boundary Layer. The lowest value of aerosol optical depth is observed for continental aerosols, from West directions with less free tropospheric contribution. The largest lidar ratios, of the order of 70 sr, are found for biomass burning aerosols. A significant and distinct correlation between lidar ratio and backscatter related Ångström exponent values were estimated for different aerosol categories. Scatter plot between lidar ratio values and Ångström exponent values for local and continental polluted aerosols does not show a significant correlation, with a large variation in both parameters possibly due to variable absorption characteristics of these aerosols. Finally for continental aerosols with west and northwest directions that follow downward movement when arriving at our site constantly low lidar ratios almost independent of size are found.
Atmospheric influence on a laser beam observed on the OICETS – ARTEMIS communication demonstration link
Authors: Löscher A.
Published: May 2010

Abstract. In 2006 bi-directional optical inter-satellite communication experiments have been conducted between the Japan Aerospace Exploration Agency (JAXA) Optical Inter-orbit Communications Engineering Test Satellite (OICETS) and the European Space Agency (ESA) multi purpose telecommunications and technology demonstration satellite (Advanced Relay and Technology MISsion) ARTEMIS. On 5 April 2006 an experiment was successfully carried out maintaining the inter-satellite link during OICETS's setting behind the Earth limb until the signal was lost. This setup resembles an occultation observation where the influence of Earth's atmosphere is evident in the power fluctuations recorded at ARTEMIS's (and OICETS's) receiver. These fluctuations are not existing or at a low level at a link path above the atmosphere and steadily increase as OICETS sets behind the horizon until the tracking of the signal is lost. This specific experiment was performed only once since atmospheric science was not the goal of this demonstration. Nevertheless this kind of data, if available more frequently in future, can help to study atmospheric turbulence and validate respective models. The data presented here had been recorded at ARTEMIS.
Tracing carbon assimilation in endosymbiotic deep-sea hydrothermal vent Mytilid fatty acids by 13C-fingerprinting
Authors: Riou V. , Bouillon S. , Serrão Santos R. , Dehairs F. , Colaço A.
Published: May 2010

Abstract. Bathymodiolus azoricus mussels thrive at Mid-Atlantic Ridge hydrothermal vents, where part of their energy requirements are met via an endosymbiotic association with chemolithotrophic and methanotrophic bacteria. In an effort to describe phenotypic characteristics of the two bacterial endosymbionts and to assess their ability to assimilate CO2, CH4 and multi-carbon compounds, we performed experiments in aquaria using 13C-labeled NaHCO3 (in the presence of H2S), CH4 or amino-acids and traced the incorporation of 13C into total and phospholipid fatty acids (tFA and PLFA, respectively). 14:0, 15:0, 16:1(n-7)c+t and 18:1(n-7)c+t PLFA were labeled in the presence of H13CO3- (+H2S) and 13CH4, while the 12:0 compound became labeled only in the presence of H13CO3− (+H2S). In contrast, the 16:1(n-9), 16:1(n-8) and (n-6), 18:1(n-8)c and (n-7), 20:1(n-7) and 18:2(n-7) PLFA were only labeled in the presence of 13CH4. Some of these symbiont-specific fatty acids also appeared to be labeled in mussel gill tFA when incubated with 13C-enriched amino acids, and so were mussel-specific fatty acids such as 22:2(n-7,15). Our results provide experimental evidence for the potential of specific fatty acid markers to distinguish between the two endosymbiotic bacteria, shedding new light on C1 and multi-carbon compound metabolic pathways in B. azoricus and its symbionts.
Adding injury to insult: unexpected rejection leads to more aggressive responses
Authors: Wesselmann Eric D. , Butler Fionnuala A. , Williams Kipling D. , Pickett Cynthia L.
Published: May 2010

Previous research indicates that rejection by a group causes aggressive responses. However, in these previous studies, rejected participants were led to believe that they were liked and accepted before the rejection; likely, this rejection was highly unanticipated. Sociometer theory (Leary et al., 1995) proposes the existence of a psychological mechanism (a “sociometer”) that enables individuals to detect potential rejection via others' reactions; a properly working sociometer affords a person predictive control over an interaction. We hypothesized the lack of predictive control inherent in previous rejection studies was a critical contributor to participants' aggressive responses; predictive control should lead to decreased aggression. To test this, we manipulated predictive control by varying confederate behavior toward participants before a rejection manipulation. Results indicate that unpredictable rejection undermined participants' belief that they could predict other's behavior (i.e., led to the perception of a broken sociometer) and led to higher levels of aggression. Aggr. Behav. 36:232–237, 2010. © 2010 Wiley‐Liss, Inc.
Organocatalyzed Highly Enantioselective and anti‐Selective Construction of γ‐Butenolides through Vinylogous Mukaiyama Aldol Reaction
Authors: Zhu Ning , Ma Bao‐Chun , Zhang Yong , Wang Wei
Published: May 2010

The formation of chiral γ‐butenolides has been achieved with good yields (up to 90%), high enantioselectivity (up to 91%) and diastereoselectivity (up to 9/1, anti‐selective) through an organocatalyzed vinylogous Mukaiyama aldol reaction of 2‐(trimethylsilyloxy)furan and aldehydes. A wide range of chiral γ‐butenolides was obtained under mild conditions by this methodology.
Gold/Acid‐Cocatalyzed Regiodivergent Preparation of Bridged Ketals via Direct Bis‐Oxycyclization of Alkynic Acetonides
Authors: Alcaide Benito , Almendros Pedro , Carrascosa Rocío , Torres M. Rosario
Published: May 2010

The regioselective metal/acid co‐catalyzed direct bis‐oxycyclization of alkynyldioxolanes allows the efficient synthesis of optically pure bi‐ and tricyclic bridged acetal systems.
Regioselective Functionalization of the Imidazole Ring via Transition Metal‐Catalyzed CN and CC Bond Forming Reactions
Authors: Bellina Fabio , Rossi Renzo
Published: May 2010

Functionalized imidazole derivatives include compounds that are known to possess a broad range of significant biological properties or are important templates in medicinal chemistry. In the light of the importance of these heteroaromatic compounds a great deal of attention has been given to their synthesis and, in the past years, a number of methods has been described in the literature allowing for the construction of the heteroaromatic core of these substances by cyclization protocols. However, in recent years, much more attention has been focused on the design and development of efficient protocols that are based on the selective functionalization of the imidazole ring at the N‐1, C‐2, C‐4 or C‐5 position via transition metal‐catalyzed reactions and enable the synthesis of imidazole derivatives, including bioactive and/or naturally occurring compounds, which cannot be accessed by other means. This critical review with 439 references covers developments in this hot area of research up to July 2009 and includes a description of synthetically important, regioselective transition metal‐catalyzed Csp2‐N, Csp‐N, Csp3‐N, Csp2‐Csp2, and Csp‐Csp2 bond forming methods, their applications, and limitations.
Visualizing polysemy using LSA and the predication algorithm
Authors: Jorge‐Botana Guillermo , León José A. , Olmos Ricardo , Hassan‐Montero Yusef
Published: May 2010

Context is a determining factor in language and plays a decisive role in polysemic words. Several psycholinguistically motivated algorithms have been proposed to emulate human management of context, under the assumption that the value of a word is evanescent and takes on meaning only in interaction with other structures. The predication algorithm (Kintsch, 2001), for example, uses a vector representation of the words produced by LSA (Latent Semantic Analysis) to dynamically simulate the comprehension of predications and even of predicative metaphors. The objective of this study was to predict some unwanted effects that could be present in vector‐space models when extracting different meanings of a polysemic word (predominant meaning inundation, lack of precision, and low‐level definition), and propose ideas based on the predication algorithm for avoiding them. Our first step was to visualize such unwanted phenomena and also the effect of solutions. We use different methods to extract the meanings for a polysemic word (without context, vector sum, and predication algorithm). Our second step was to conduct an analysis of variance to compare such methods and measure the impact of potential solutions. Results support the idea that a human‐based computational algorithm like the predication algorithm can take into account features that ensure more accurate representations of the structures we seek to extract. Theoretical assumptions and their repercussions are discussed.
Hydrogen Storage Properties of Ca(BH4)2–LiNH2 System
Authors: Chu Hailiang , Xiong Zhitao , Wu Guotao , Guo Jianping , Zheng Xueli , He Teng , Wu Chengzhang , Chen Ping
Published: May 2010

Ca(BH4)2 is one of the promising candidates for hydrogen storage materials because of its high gravimetric and volumetric hydrogen capacity. However, its high dehydrogenation temperature and limited reversibility has been a hurdle for its practical applications. In an effort to overcome these barriers and to adjust the thermal stability, we make a composite system Ca(BH4)2–LiNH2. Interaction of Ca(BH4)2 and LiNH2 leads to decreased dehydrogenation temperatures and increased hydrogen desorption capacity in comparison to pristine Ca(BH4)2. More than 7 wt % of hydrogen can be detached at a temperature as low as approximately 178 °C from the cobalt‐catalyzed Ca(BH4)2–4 LiNH2 system.
Eine Frage der Politik: Wissenschaft und Ideologie im 21. Jahrhundert
Authors: Wahrig Bettina
Published: May 2010

A Political Matter: Science and Ideology in the 21st Century. In the last two decades, history of science and science studies have been quite reluctant to adopt the notion of ideology when analyzing the dynamics of science. This may be an effect of the decreasing popularity of neo‐marxist approaches within this disciplinary field; but it is also due to the fact that alternative approaches have been developed, for example Michel Foucault's notion of problematization, Roland Barthes' semiotic mythology, Bruno Latour's re‐interpretation of the ontological difference between fact and fetish in science, or Donna Haraway's semi‐fictional re‐narrations of the techno‐scientific world. This contribution undertakes to sketch the impact of two strands of 19th century immanentism on the authors named above, and on their use of concepts related to the notion of ideology, namely fetish, fetishism, myth and mythology respectively. It is argued that in some respect, Marx' concept of commodity fetishism is worth being re‐examined, since it articulates a dialectical relation of ‘reality’ and ‘seeming’, and its impact on Barthes' mythology is deeper than it might appear at first glance.
Multivariate data analysis on historical IPV production data for better process understanding and future improvements
Authors: Thomassen Yvonne E. , van Sprang Eric N.M. , van der Pol Leo A. , Bakker Wilfried A.M.
Published: May 2010

Historical manufacturing data can potentially harbor a wealth of information for process optimization and enhancement of efficiency and robustness. To extract useful data multivariate data analysis (MVDA) using projection methods is often applied. In this contribution, the results obtained from applying MVDA on data from inactivated polio vaccine (IPV) production runs are described. Data from over 50 batches at two different production scales (700‐L and 1,500‐L) were available. The explorative analysis performed on single unit operations indicated consistent manufacturing. Known outliers (e.g., rejected batches) were identified using principal component analysis (PCA). The source of operational variation was pinpointed to variation of input such as media. Other relevant process parameters were in control and, using this manufacturing data, could not be correlated to product quality attributes. The gained knowledge of the IPV production process, not only from the MVDA, but also from digitalizing the available historical data, has proven to be useful for troubleshooting, understanding limitations of available data and seeing the opportunity for improvements. Biotechnol. Bioeng. 2010;107: 96–104. © 2010 Wiley Periodicals, Inc.
Azide: A Unique Dipole for Metal‐Free Bioorthogonal Ligations
Authors: Debets Marjoke F. , van der Doelen Christianus W. J. , Rutjes Floris P. J. T. , van Delft Floris L.
Published: May 2010

Covalently bound azide on a (small) organic molecule or a (large) biomolecular structure has proven an important handle for bioconjugation. Azides are readily introduced, small, and stable, yet undergo smooth ligation with a range of reactive probes under mild conditions. In particular, the potential of azides to undergo metal‐free reactions with strained unsaturated systems has inspired the development of an increasing number of reactive probes, which are comprehensively summarized here. For each individual probe, the synthetic preparation is described, together with reaction kinetics and the full range of applications, from materials science to glycoprofiling. Finally, a qualitative and quantitative comparison of azido‐reactive probes is provided.
Multivalent Display and Receptor‐Mediated Endocytosis of Transferrin on Virus‐Like Particles
Authors: Banerjee Deboshri , Liu Allen P. , Voss Neil R. , Schmid Sandra L. , Finn M. G.
Published: May 2010

The structurally regular and stable self‐assembled capsids derived from viruses can be used as scaffolds for the display of multiple copies of cell‐ and tissue‐targeting molecules and therapeutic agents in a convenient and well‐defined manner. The human iron‐transfer protein transferrin, a high affinity ligand for receptors upregulated in a variety of cancers, has been arrayed on the exterior surface of the protein capsid of bacteriophage Qβ. Selective oxidation of the sialic acid residues on the glycan chains of transferrin was followed by introduction of a terminal alkyne functionality through an oxime linkage. Attachment of the protein to azide‐functionalized Qβ capsid particles in an orientation allowing access to the receptor binding site was accomplished by the CuI‐catalyzed azide–alkyne cycloaddition (CuAAC) click reaction. Transferrin conjugation to Qβ particles allowed specific recognition by transferrin receptors and cellular internalization through clathrin‐mediated endocytosis, as determined by fluorescence microscopy on cells expressing GFP‐labeled clathrin light chains. By testing Qβ particles bearing different numbers of transferrin molecules, it was demonstrated that cellular uptake was proportional to ligand density, but that internalization was inhibited by equivalent concentrations of free transferrin. These results suggest that cell targeting with transferrin can be improved by local concentration (avidity) effects.
Structural Optimization of Photoswitch Ligands for Surface Attachment of α‐Chymotrypsin and Regulation of Its Surface Binding
Authors: Pearson David , Abell Andrew D.
Published: May 2010

A modified gold surface that allows photoregulated binding of α‐chymotrypsin has previously been reported. Here the development of this surface is reported, through the synthesis of a series of trifluoromethyl ketones and α‐keto esters containing the azobenzene group and a surface attachment group as photoswitch inhibitors of α‐chymotrypsin. All of the compounds are inhibitors of the enzyme, with activity that can be modulated by photoisomerization. The best photoswitch shows a reversible change in IC50 inhibition constant of >5.3 times on photoisomerization. The trifluoromethyl ketone 1 exhibited excellent photoswitching and was attached to a gold surface in a two‐step procedure involving an azide–alkyne cycloaddition. The resulting modified surface bound α‐chymotrypsin to a degree that could be modulated by UV/Vis irradiation, showing “slow‐tight” enzyme binding as observed for inhibitors in solution.
Chemoselective Catalysis with Organosoluble Lewis Acidic Polyoxotungstates
Authors: Dupré Nathalie , Rémy Pauline , Micoine Kévin , Boglio Cécile , Thorimbert Serge , Lacôte Emmanuel , Hasenknopf Bernold , Malacria Max
Published: May 2010

The preparation of new organosoluble Lewis acidic polyoxometalates (POMs) is reported. These complexes were prepared by the incorporation of Zr, Sc, and Y atoms into the corresponding monolacunary Dawson [P2W17O61]10− and Keggin [PW11O39]7− polyoxotungstates. The catalytic activity of these compounds was evaluated for CC bond formation in the Diels–Alder, Mannich, and Mukaiyama‐type reactions. Comparisons with previously described Lewis acidic POMs are reported. Competitive reactions between imines and aldehydes or between various imines demonstrated that fine tuning of the reactivity could be reached by varying the metal atom incorporated into the polyanionic framework. A series of experiments that employed pyridine derivatives allowed us to distinguish between the Lewis and induced Brønsted acidity of the POMs. These catalysts activate imines in a Lewis acidic way, whereas aldehydes are activated by indirect Brønsted catalysis.
Pyrrolidinyl–Camphor Derivatives as a New Class of Organocatalyst for Direct Asymmetric Michael Addition of Aldehydes and Ketones to β‐Nitroalkenes
Authors: Ting Ying‐Fang , Chang Chihliang , Reddy Raju Jannapu , Magar Dhananjay R. , Chen Kwunmin
Published: May 2010

Practical and convenient synthetic routes have been developed for the synthesis of a new class of pyrrolidinyl–camphor derivatives (7 a–h). These novel compounds were screened as catalysts for the direct Michael addition of symmetrical α,α‐disubstituted aldehydes to β‐nitroalkenes. When this asymmetric transformation was catalyzed by organocatalyst 7 f, the desired Michael adducts were obtained in high chemical yields, with high to excellent stereoselectivities (up to 98:2 diastereomeric ratio (d.r.) and 99 % enantiomeric excess (ee)). The scope of the catalytic system was expanded to encompass various aldehydes and ketones as the donor sources. The synthetic application was demonstrated by the synthesis of a tetrasubstituted‐cyclohexane derivative from (S)‐citronellal, with high stereoselectivity.
Imaging monocytes with iron oxide nanoparticles targeted towards the monocyte integrin MAC‐1 (CD11b/CD18) does not result in improved atherosclerotic plaque detection by in vivo MRI
Authors: von zur Muhlen C. , Fink‐Petri A. , Salaklang J. , Paul D. , Neudorfer I. , Berti V. , Merkle A. , Peter K. , Bode C. , von Elverfeldt D.
Published: May 2010

Imaging of macrophages with superparamagnetic iron oxide particles (SPIO) has been performed to improve detection of atherosclerotic plaque inflammation in human and mouse studies by molecular magnetic resonance imaging (MRI). Since affinity of the monocyte/macrophage integrin MAC‐1 (CD11b/CD18) is upregulated in inflammation, we generated a contrast agent targeting CD11b (CD11b‐SPIOs) for improved macrophage detection in plaques. CD11b‐SPIOs and non‐targeted SPIOs (control‐SPIOs) were incubated in vitro with human monocytes/macrophages. As quantified by SPIO‐induced MRI signal extinction, intracellular iron‐content was significantly higher in monoytes/macrophages incubated with CD11b‐SPIO than with control‐SPIO in vitro (p < 0.05), suggesting an improved uptake of CD11b‐SPIOs into monocytes. Therefore, the aortic arch (AA) and vessel branches of ApoE−/−‐knockout mice on a Western‐type diet were imaged before and 48 h after contrast agent injection of either CD11b‐SPIOs or control‐SPIOs, using a 9.4 T animal MRI system. The SPIO‐induced change in the MRI signal was quantified, as well as the macrophage‐content by anti‐CD68 immunhistochemistry and the iron‐content by Prussian‐blue staining. However, SPIO‐induced signal extinction in in vivo‐MRI was similar in CD11b‐SPIO and control‐SPIO‐injected animals, with a non‐significant trend towards an improved uptake of CD11b‐SPIOs in the subclavian artery and subsections of the AA. These data correlated well with the results obtained by histology. Although in vitro MRI‐data indicated an increased uptake of targeted CD11b‐SPIOs in monocytes/macrophages, in vivo mouse data do not allow improved atherosclerotic plaque detection compared WITH non‐targeted SPIOs. Therefore, CD11b‐targeted MRI contrast labelling of monocytes/macrophages does not seem to be a successful strategy in stable atherosclerotic plaques such as found in the ApoE−/−‐knockout‐model. However, the impressive correlation between MRI and histology data encourages further development of inflammation‐ and plaque‐specific contrast agents for vulnerable plaque imaging. Copyright © 2010 John Wiley & Sons, Ltd.
Contention‐tolerant crossbar packet switches
Authors: Qu Guannan , Chang Hyung Jae , Wang Jianping , Fang Zhiyi , Zheng S. Q.
Published: May 2010

We propose an innovative agile crossbar switch architecture called contention‐tolerant crossbar, denoted by CTC(N). Unlike the conventional crossbar and the crossbar with crosspoint buffers, which require complex hardware resolvers to grant one out of multiple output requests, CTC(N) can tolerate output contentions by a pipelining mechanism, with pipeline stages implemented as buffers in input ports. These buffers are used to decouple the scheduling task intoNindependent parts in such a way thatNschedulers are located inNinput ports, and they operate independently and in parallel. Without using arbiters and/or crosspoint buffers that require additional chip area, the CTC(N) switch is more scalable than existing crossbars. We analyze the throughput of CTC(N) switch, and find 63% throughput bottleneck. For achieving 100%, we consider two approaches: using internal speedup and using space multiplexing without internal speedup. We prove that 100% throughput can be achieved with internal speedup 2 or using two layers of CTC(N) fabric mathematically. Our simulation results validate our theoretical analysis. Copyright © 2010 John Wiley & Sons, Ltd.
Mortality of eating disorders: A follow‐up study of treatment in a specialist unit 1974–2000
Authors: Rosling Agneta M. , Sparén Pär , Norring Claes , von Knorring Anne‐Liis
Published: May 2010

Objective:

To study excess mortality, causes of death, and co‐morbidity in patients with eating disorder (ED), treated in a Swedish specialist facility.

Method:

A retrospective cohort study of 201 patients with ED followed from 1974 to year 2001 in the Swedish Causes of Death Register (SCODR). Standardized mortality ratio (SMR) was calculated with respect to the Swedish population, by gender, age, and calendar time.

Results:

In the complete follow‐up of 201 patients, 23 had died. At a mean follow‐up of 14.3 years the overall SMR was 10. Patients with body mass index (BMI) over 11.5 had an average SMR of about 7 and for those with BMI lower than 11.5 had SMR above 30. Six patients died from AN/starvation, nine due to suicide, and eight from other causes.

Discussion:

SMR in anorexia nervosa (AN) is high but not in bulimia nervosa. A risk stratification of AN, based on BMI is suggested. © 2010 by Wiley Periodicals, Inc. (Int J Eat Disord 2011; 44:304–310)
Associations between body checking and disordered eating behaviors in nonclinical women
Authors: Haase Anne M. , Mountford Victoria , Waller Glenn
Published: May 2010

Objective:

Recent research suggests that body checking cognitions and behaviors are differentially associated with pathological eating behaviors in clinical women. However, it is unknown whether similar associations exist in nonclinical populations. The aim of this study is to examine whether body checking (cognitions and behaviors) is associated with pathological eating behaviors in a nonclinical sample of women.

Method:

Validated measures of pathological eating behaviors, body checking cognitions, and body checking behaviors were completed by 342 nonclinical university women.

Results:

Women engaging in binging (objective and subjective), purging, restraint, and excessive exercise reported consistently higher scores across all body checking cognitions and behaviors. All body checking cognitions and behaviors independently contributed to distinguishing those who reported each behavior as opposed to those who did not. The predicted classification was most accurate for the cardinal diagnostic symptoms for bulimia—objective binging and purging.

Discussion:

Body checking cognitions are implicated in the development of pathological eating behaviors in nonclinical populations, requiring consideration for planning prevention programs. © 2010 by Wiley Periodicals, Inc. (Int J Eat Disord 2011; 44:465–468)
Aromatic Nitrogen Donors for Efficient Copper(I)–NHC CuAAC under Reductant‐Free Conditions
Authors: Teyssot Marie‐Laure , Nauton Lionel , Canet Jean‐Louis , Cisnetti Federico , Chevry Aurélien , Gautier Arnaud
Published: May 2010

Copper(I)‐catalysed azide–alkyne cycloaddition (CuAAC) has been successfully conducted under reductant‐free conditions. The catalytic system consisted of a combination of a copper(I)–N‐heterocyclic carbene complex and aromatic N‐donors. The catalyst is stable and can be stored, thus rendering the reaction valuable for routine use.
The pen is mightier than the word: Object priming of evaluative standards
Authors: Rutchick Abraham M. , Slepian Michael L. , Ferris Bennett D.
Published: May 2010

Because red pens are closely associated with error‐marking and poor performance, the use of red pens when correcting student work can activate these concepts. People using red pens to complete a word‐stem task completed more words related to errors and poor performance than did people using black pens (Study 1), suggesting relatively greater accessibility of these concepts. Moreover, people using red pens to correct essays marked more errors (Study 2) and awarded lower grades (Study 3) than people using blue pens. Thus, despite teachers' efforts to free themselves from extraneous influences when grading, the very act of picking up a red pen can bias their evaluations. Copyright © 2010 John Wiley & Sons, Ltd.
Will moral outrage stand up?: Distinguishing among emotional reactions to a moral violation
Authors: O'Mara Erin M. , Jackson Lydia E. , Batson C. Daniel , Gaertner Lowell
Published: May 2010

Moral outrage—anger at violation of a moral standard—is claimed to be a prevalent and powerful moral emotion. However, evidence for moral outrage has been compromised by failure to distinguish it from personal anger—anger at harm to self—felt by victims of a moral violation. Although it does not seem possible to distinguish these two forms of anger by measurement, it is possible to do so by experimental manipulation of their distinct eliciting conditions. Extending previous research, the current study manipulated how a victim (self vs. stranger) was excluded (fairly vs. unfairly) from a favorable experience. Reported anger and behavioral retribution provided evidence of personal anger and revenge, not of moral outrage. These findings suggest that the prevalence and power of moral outrage has been exaggerated. Copyright © 2010 John Wiley & Sons, Ltd.
Objectification leads to depersonalization: The denial of mind and moral concern to objectified others
Authors: Loughnan Steve , Haslam Nick , Murnane Tess , Vaes Jeroen , Reynolds Catherine , Suitner Caterina
Published: May 2010

Philosophers have argued that when people are objectified they are treated as if they lack the mental states and moral status associated with personhood. These aspects of objectification have been neglected by psychologists. This research investigates the role of depersonalization in objectification. In Study 1, objectified women were attributed less mind and were accorded lesser moral status than non‐objectified women. In Study 2, we replicated this effect with male and female targets and extended it to include perceptions of competence and pain attribution. Further, we explored whether target and perceiver gender qualify depersonalization. Overall, this research indicates that when people are objectified they are denied personhood. Copyright © 2010 John Wiley & Sons, Ltd.
Somatic alterations in the melanoma genome: A high‐resolution array‐based comparative genomic hybridization study
Authors: Gast Andreas , Scherer Dominique , Chen Bowang , Bloethner Sandra , Melchert Stephanie , Sucker Antje , Hemminki Kari , Schadendorf Dirk , Kumar Rajiv
Published: May 2010

We performed DNA microarray‐based comparative genomic hybridization to identify somatic alterations specific to melanoma genome in 60 human cell lines from metastasized melanoma and from 44 corresponding peripheral blood mononuclear cells. Our data showed gross but nonrandom somatic changes specific to the tumor genome. Although the CDKN2A (78%) and PTEN (70%) loci were the major targets of mono‐allelic and bi‐allelic deletions, amplifications affected loci with BRAF (53%) and NRAS (12%) as well as EGFR (52%), MITF (40%), NOTCH2 (35%), CCND1 (18%), MDM2 (18%), CCNE1 (10%), and CDK4 (8%). The amplified loci carried additional genes, many of which could potentially play a role in melanoma. Distinct patterns of copy number changes showed that alterations in CDKN2A tended to be more clustered in cell lines with mutations in the BRAF and NRAS genes; the PTEN locus was targeted mainly in conjunction with BRAF mutations. Amplification of CCND1, CDK4, and other loci was significantly increased in cell lines without BRAF‐NRAS mutations and so was the loss of chromosome arms 13q and 16q. Our data suggest involvement of distinct genetic pathways that are driven either through oncogenic BRAF and NRAS mutations complemented by aberrations in the CDKN2A and PTEN genes or involve amplification of oncogenic genomic loci and loss of 13q and 16q. It also emerges that each tumor besides being affected by major and most common somatic genetic alterations also acquires additional genetic alterations that could be crucial in determining response to small molecular inhibitors that are being currently pursued. © 2010 Wiley‐Liss, Inc.