bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective Targeting of B Cells with Agonistic Anti-CD40 Is an Efficacious Strategy for the Generation of Induced Regulatory T2-Like B Cells and for the Suppression of Lupus in MRL/lpr Mice
Authors: Blair Paul A. , Chavez-Rueda Karina A. , Evans Jamie G. , Shlomchik Mark J. , Eddaoudi Ayad , Isenberg David A. , Ehrenstein Michael R. , Mauri Claudia
Published: March 2009

We have previously reported that IL-10+ regulatory B cells, known to play an important role in controlling autoimmunity and inflammatory disorders, are contained within the transitional 2 immature (T2) B cell pool (T2 Bregs). Therapeutic strategies facilitating their enrichment or enhancing their suppressive activity are highly attractive. In this study, we report that agonistic anti-CD40 specifically targets T2 B cells and enriches Bregs upon short-term in vitro culture. Although transfer of unmanipulated T2 B cells, isolated from mice with established lupus, failed to confer protection to diseased mice, transfer of in vitro anti-CD40-generated T2 B cells (T2-like-Bregs) significantly improved renal disease and survival by an IL-10-dependent mechanism. T2-like-Bregs readily accumulated in the spleen after transfer, suppressed Th1 responses, induced the differentiation of IL-10+CD4+T cells, and conveyed a regulatory effect to CD4+T cells. In addition, in vivo administration of agonistic anti-CD40, currently on trial for the treatment of cancer, halted and reversed established lupus. Taken together, our results suggest a novel cellular approach for the amelioration of experimental lupus.
C3a and C5a Are Chemotactic Factors for Human Mesenchymal Stem Cells, Which Cause Prolonged ERK1/2 Phosphorylation
Authors: Schraufstatter Ingrid U. , DiScipio Richard G. , Zhao Ming , Khaldoyanidi Sophia K.
Published: March 2009

Mesenchymal stem cells (MSCs) have a great potential for tissue repair, especially if they can be delivered efficiently to sites of tissue injury. Since complement activation occurs whenever there is tissue damage, the effects of the complement activation products C3a and C5a on MSCs were examined. Both C3a and C5a were chemoattractants for human bone marrow-derived MSCs, which expressed both the C3a receptor (C3aR) and the C5a receptor (C5aR; CD88) on the cell surface. Specific C3aR and C5aR inhibitors blocked the chemotactic response, as did pertussis toxin, indicating that the response was mediated by the known anaphylatoxin receptors in a Gi activation-dependent fashion. While C5a causes strong and prolonged activation of various signaling pathways in many different cell types, the response observed with C3a is generally transient and weak. However, we show herein that in MSCs both C3a and C5a caused prolonged and robust ERK1/2 and Akt phosphorylation. Phospho-ERK1/2 was translocated to the nucleus in both C3a and C5a-stimulated MSCs, which was associated with subsequent phosphorylation of the transcription factor Elk, which could not be detected in other cell types stimulated with C3a. More surprisingly, the C3aR itself was translocated to the nucleus in C3a-stimulated MSCs, especially at low cell densities. Since nuclear activation/translocation of G protein-coupled receptors has been shown to induce long-term effects, this novel observation implies that C3a exerts far-reaching consequences on MSC biology. These results suggest that the anaphylatoxins C3a and C5a present in injured tissues contribute to the recruitment of MSCs and regulation of their behavior.
Contribution of Nonneutralizing Vaccine-Elicited Antibody Activities to Improved Protective Efficacy in Rhesus Macaques Immunized with Tat/Env Compared with Multigenic Vaccines
Authors: Florese Ruth H. , Demberg Thorsten , Xiao Peng , Kuller LaRene , Larsen Kay , Summers L. Ebonita , Venzon David , Cafaro Aurelio , Ensoli Barbara , Robert-Guroff Marjorie
Published: March 2009

Previously, chronic-phase protection against SHIV89.6P challenge was significantly greater in macaques primed with replicating adenovirus type 5 host range mutant (Ad5hr) recombinants encoding HIVtat and env and boosted with Tat and Env protein compared with macaques primed with multigenic adenovirus recombinants (HIVtat, HIVenv, SIVgag, SIVnef) and boosted with Tat, Env, and Nef proteins. The greater protection was correlated with Tat- and Env-binding Abs. Because the macaques lacked SHIV89.6P-neutralizing activity prechallenge, we investigated whether Ab-dependent cellular cytotoxicity (ADCC) and Ab-dependent cell-mediated viral inhibition (ADCVI) might exert a protective effect. We clearly show that Tat can serve as an ADCC target, although the Tat-specific activity elicited did not correlate with better protection. However, Env-specific ADCC activity was consistently higher in the Tat/Env group, with sustained cell killing postchallenge exhibited at higher levels (p < 0.00001) for a longer duration (p = 0.0002) compared with the multigenic group. ADCVI was similarly higher in the Tat/Env group and significantly correlated with reduced acute-phase viremia at wk 2 and 4 postchallenge (p = 0.046 and 0.011, respectively). Viral-specific IgG and IgA Abs in mucosal secretions were elicited but did not influence the outcome of the i.v. SHIV89.6P challenge. The higher ADCC and ADCVI activities seen in the Tat/Env group provide a plausible mechanism responsible for the greater chronic-phase protection. Because Tat is known to enhance cell-mediated immunity to coadministered Ags, further studies should explore its impact on Ab induction so that it may be optimally incorporated into HIV vaccine regimens.
Lipoxin A4: Anti-Inflammatory and Anti-Angiogenic Impact on Endothelial Cells
Authors: Baker Nicole , O'Meara Sarah J. , Scannell Michael , Maderna Paola , Godson Catherine
Published: March 2009

Lipoxins (LX) are a class of eicosanoid that possesses a wide spectrum of antiinflammatory and proresolution bioactions. Here we have investigated the impact of the endogenously produced eicosanoid LXA4 on endothelial cell inflammatory, proliferative, and antigenic responses. Using HUVECs we demonstrate that LXA4 inhibits vascular endothelial growth factor (VEGF)-stimulated inflammatory responses including IL-6, TNF-α, IFN-γ and IL-8 secretion, as well as endothelial ICAM-1 expression. Interestingly, LXA4 up-regulated IL-10 production from HUVECs. Consistent with these antiinflammatory and proresolution responses to LXA4, we demonstrate that LXA4 inhibited leukotriene D4 and VEGF-stimulated proliferation and angiogenesis as determined by tube formation of HUVECs. We have explored the underlying molecular mechanisms and demonstrate that LXA4 pretreatment is associated with the decrease of VEGF-stimulated VEGF receptor 2 (KDR/FLK-1) phosphorylation and downstream signaling events including activation of phospholipase C-γ, ERK1/2, and Akt.
Cell-Autonomous Role for NF-κB in Immature Bone Marrow B Cells
Authors: Claudio Estefania , Saret Sun , Wang Hongshan , Siebenlist Ulrich
Published: March 2009

The NF-κB transcription factors have many essential functions in B cells, such as during differentiation and proliferation of Ag-challenged mature B cells, but also during final maturation of developing B cells in the spleen. Among the various specific functions NF-κB factors carry out in these biologic contexts, their ability to assure the survival of mature and maturing B cells in the periphery stands out. Less clear is what if any roles NF-κB factors play during earlier stages of B cell development in the bone marrow. Using mice deficient in both NF-κB1 and NF-κB2, which are thus partially compromised in both the classical and alternative activation pathways, we demonstrate a B cell-autonomous contribution of NF-κB to the survival of immature B cells in the bone marrow. NF-κB1 and NF-κB2 also play a role during the earlier transition from proB to late preB cells; however, in this context these factors do not act in a B cell-autonomous fashion. Although NF-κB1 and NF-κB2 are not absolutely required for survival and progression of immature B cells in the bone marrow, they nevertheless make a significant contribution that marks the beginning of the profound cell-autonomous control these factors exert during all subsequent stages of B cell development. Therefore, the lifelong dependency of B cells on NF-κB-mediated survival functions is set in motion at the time of first expression of a full BCR.
Cytoprotective Function of Heme Oxygenase 1 Induced by a Nitrated Cyclic Nucleotide Formed during Murine Salmonellosis
Authors: Zaki Mohammad Hasan , Fujii Shigemoto , Okamoto Tatsuya , Islam Sabrina , Khan Shahzada , Ahmed Khandaker Ahtesham , Sawa Tomohiro , Akaike Takaaki
Published: March 2009

Signaling mechanisms of NO-mediated host defense are yet to be elucidated. In this study, we report a unique signal pathway for cytoprotection during Salmonella infection that involves heme oxygenase 1 (HO-1) induced by a nitrated cyclic nucleotide, 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP). Wild-type C57BL/6 mice and C57BL/6 mice lacking inducible NO synthase (iNOS) were infected with Salmonella enterica serovar Typhimurium LT2. HO-1 was markedly up-regulated during the infection, the level being significantly higher in wild-type mice than in iNOS-deficient mice. HO-1 up-regulation was associated with 8-nitro-cGMP formation detected immunohistochemically in Salmonella-infected mouse liver and peritoneal macrophages. 8-Nitro-cGMP either exogenously added or formed endogenously induced HO-1 in cultured macrophages infected with Salmonella. HO-1 inhibition by polyethylene glycol-conjugated zinc-protoporphyrin IX impaired intracellular killing of bacteria in mouse liver and in both RAW 264 cells and peritoneal macrophages. Infection-associated apoptosis was also markedly increased in polyethylene glycol-conjugated zinc-protoporphyrin IX-treated mouse liver cells and cultured macrophages. This effect of HO-1 inhibition was further confirmed by using HO-1 short interfering RNA in peritoneal macrophages. Our results suggest that HO-1 induced by NO-mediated 8-nitro-cGMP formation contributes, via its potent cytoprotective function, to host defense during murine salmonellosis.
ESAT-6 Inhibits Production of IFN-γ by Mycobacterium tuberculosis-Responsive Human T Cells
Authors: Wang Xisheng , Barnes Peter F. , Dobos-Elder Karen M. , Townsend James C. , Chung Yoon-tae , Shams Homayoun , Weis Stephen E. , Samten Buka
Published: March 2009

The Mycobacterium tuberculosis early secreted Ag of 6 kDa (ESAT-6) is a potent Ag for human T cells and is a putative vaccine candidate. However, ESAT-6 also contributes to virulence in animal models, mediates cellular cytolysis, and inhibits IL-12 production by mononuclear phagocytes. We evaluated the effects of ESAT-6 and its molecular chaperone, culture filtrate protein of 10 kDa (CFP10), on the capacity of human T cells to produce IFN-γ and proliferate in response to TCR activation. Recombinant ESAT-6, but not CFP10, markedly inhibited IFN-γ production by T cells stimulated with M. tuberculosis or with the combination of anti-CD3 and anti-CD28, in a dose-dependent manner. ESAT-6 also inhibited T cell production of IL-17 and TNF-α but not IL-2. Preincubation of ESAT-6 with CFP10 under conditions that favor dimer formation did not affect inhibition of IFN-γ. ESAT-6 decreased IFN-γ transcription and reduced expression of the transcription factors, ATF-2 and c-Jun, which normally bind to the IFN-γ proximal promoter and stimulate mRNA expression. ESAT-6 inhibited T cell IFN-γ secretion through mechanisms that did not involve cellular cytotoxicity or apoptosis. ESAT-6, but not CFP10, bound to T cells and inhibited expression of early activation markers without reducing activation of ZAP70. We conclude that ESAT-6 directly inhibits human T cell responses to mycobacterial Ags by affecting TCR signaling pathways downstream of ZAP70.
Ectopic Germinal Centers Are Rare in Sjögren’s Syndrome Salivary Glands and Do Not Exclude Autoreactive B Cells
Authors: Le Pottier Laëtitia , Devauchelle Valérie , Fautrel Alain , Daridon Capucine , Saraux Alain , Youinou Pierre , Pers Jacques-Olivier
Published: March 2009

This study reports on the characterization of B cells of germinal center (GC)-like structures infiltrating the salivary glands (SGs) of patients with Sjögren’s syndrome. Eight two-color combinations were devised to characterize the phenotype of these B cells in 11 SG specimens selected from biopsies obtained from 40 Sjögren’s syndrome patients and three normal tonsils. The 9G4 mAb, which recognizes V4.34-encoded autoAbs, enabled us to identify autoreactive B cells. Quantitative RT-PCR was used to determine the level of mRNAs for activation-induced cytidine deaminase (AICDA), repressors and transcription factors. CD20+IgD−CD38+CD21+CD24− B cells, similar to those identified in tonsil GCs, were seen in the SGs of four patients and, and since they expressed AICDA, they were termed “real GCs”. CD20+IgD+CD38−CD21+CD24+ B cells, seen in aggregates from the remaining seven samples, were characteristically type 2 transitional B cells and marginal zone-type B cells. They lacked AICDA mRNAs and were termed “aggregates”. Real GCs from SGs contained mRNAs for Pax-5 and Bcl-6, like tonsil GC cells, whereas aggregates contained mRNAs for Notch-2, Blimp-1, IRF-4, and BR3, similar to marginal zone B cells. Further experimental data in support of this dichotomy included the restriction of CXCR5 expression to real GC cells, while sphingosine 1-phosphate receptor 1 was expressed only in aggregates. In contrast, both types of B cell clusters expressed the idiotype recognized by the 9G4 mAb. Our data indicate that, in SGs, a minority of B cell clusters represent genuine GC cells, while the majority manifest features of being type 2 transitional B cells and marginal zone cells. Interestingly, both types of B cell aggregates include autoreactive B cells.
Local Production of IFN-γ by Invariant NKT Cells Modulates Acute Lyme Carditis
Authors: Olson Chris M. , Bates Tonya C. , Izadi Hooman , Radolf Justin D. , Huber Sally A. , Boyson Jonathan E. , Anguita Juan
Published: March 2009

The Lyme disease spirochete Borrelia burgdorferi is the only known human pathogen that directly activates invariant NKT (iNKT) cells. The number and activation kinetics of iNKT cells vary greatly among different strains of mice. We now report the role of the iNKT cell response in the pathogenesis of Lyme disease using C57BL/6 mice, a strain with optimal iNKT cell activation that is resistant to the development of spirochetal-induced inflammation. During experimental infection of B6 mice with B. burgdorferi, iNKT cells localize to the inflamed heart where they are activated by CD1d-expressing macrophages. Activation of iNKT cells in vivo results in the production of IFN-γ, which we demonstrate ameliorates the severity of murine Lyme carditis by at least two mechanisms. First, IFN-γ enhances the recognition of B. burgdorferi by macrophages, leading to increased phagocytosis of the spirochete. Second, IFN-γ activation of macrophages increases the surface expression of CD1d, thereby facilitating further iNKT activation. Collectively, our data demonstrate that in the resistant background, B6, iNKT cells modulate the severity of murine Lyme carditis through the action of IFN-γ, which appears to self-renew through a positive feedback loop during infection.
Virulent Toxoplasma gondii Evade Immunity-Related GTPase-Mediated Parasite Vacuole Disruption within Primed Macrophages
Authors: Zhao Yanlin , Ferguson David J. P. , Wilson Douglas C. , Howard Jonathan C. , Sibley L. David , Yap George S.
Published: March 2009

Cytokine-activated macrophages restrain the replication of intracellular parasites and disrupt the integrity of vacuolar pathogens. In this study, we show that inducible nitric oxide synthase and the immunity-related GTPase (IRG) family member Irgm3, respectively, are required for the ability of in vivo primed macrophages to restrain the growth of Toxoplasma gondii and to destroy the parasite’s intracellular niche. Remarkably, virulent Type I strains of T. gondii evade IRG-dependent vacuolar disruption, while remaining susceptible to iNOS-dependent restriction. The ability of virulent T. gondii to escape killing by macrophages is controlled at the level of the individual vacuole and is associated with differential permissiveness for association of the IRG proteins Irga6 (IIGP1) and Irgb6 (TGTP) to the vacuolar membrane. Surprisingly, expression of the Type I ROP-18 virulence determinant in an avirulent strain did not confer the evasive phenotype. These results pinpoint evasion of vacuolar disruption by IRG proteins as a new determinant of pathogen virulence.
Apoptosome and Caspase Activation
Authors: Declercq Wim , Vandenabeele Peter
Published: March 2009

Apoptosis is an evolutionarily conserved form of cell death that executes programmed cell death during development and tissue homeostasis. Insufficient levels of apoptosis can contribute to the development of cancer, whereas excessive apoptosis is implicated in degenerative diseases, such as stroke, cardiac failure, and neurological pathologies. Since the beginning of the 1990s, our knowledge of apoptotic signaling pathways has increased tremendously. The caspase family of aspartate‐specific cysteine proteases is conserved in many species and incorporates key proteases involved in initiation and execution of apoptosis. Together with the discovery and better understanding of their activation complexes, such as the apoptosome, new strategies to modulate cell death in pathological conditions are being developed.
Circular Dichroism (CD) for Natural Products
Authors: Taniguchi Tohru , Nakanishi Koji
Published: March 2009

Circular dichroism (CD) spectroscopy is used widely for nonempirical determinations of absolute configuration. The advantages of CD spectroscopy are summarized as follows: 1) CD spectra are measurable in ultra microscale because of high sensitivity, 2) the CD exciton chirality method enables one to determine the absolute configuration in a straightforward and nonambiguous manner, and 3) the recent progress in molecular orbital (MO) computations enhances versatility of CD. The basic aspects of CD and theoretical calculations for assignment of absolute configurations are described first. This analysis is followed by an outline of the exciton chirality method and the selection of chromophores with optimal λmaxand ɛ for use in this method. The additivity relation encountered in molecules in which multiple chromophores are present is a fundamental principle that greatly simplifies the analyses of complex CD spectra that consist of complex CD extrema (i.e., maxima and minima). The examples cited are intended to illustrate the various approaches that lead to determination of absolute configurations by CD.
Fluorescence in Living Systems: Applications in Chemical Biology
Authors: Cornish Virginia W. , Gallagher Sarah S.
Published: March 2009

Increasingly, studies of biomolecules are progressing from understanding how isolated biomolecules workin vitroto asking how macromolecular machines, signaling pathways, and other biological networks function in the complex environment of the living cell. Just as chemical methods greatly impacted fundamental studies of the structure and function of biomoleculesin vitroin the last century, chemical methods are now being developed to study biomolecule functionin vivo. This review focuses on chemical biology tools being developed to provide fluorescent reporters for biomolecules in living cells. The wealth ofin vitrofluorescent reporters is the underpinning of much of this research, but it is beyond the scope of this review. Emphasis is placed on protein tagging, beginning with the fluorescent proteins and more recently moving to chemical tagging methods. In addition, chemical tools for fluorescence imaging of other classes of biomolecules and dynamic modifications to biomolecules in living cells are also overviewed.
Biocatalytic Synthesis of Natural and Non‐Natural α‐Amino Acids
Authors: Harald Gröger , Dietz Friedrich R.
Published: March 2009

The synthesis of enantiomerically pure α‐amino acids has attracted the attention of generations of organic chemists, and a broad range of efficient synthetic methods is already known. The developed synthetic approaches are based on different concepts such as 1) “classic” chemical resolution (by means of diastereomeric salt pair formation), 2) chiral pool syntheses making use of easily accessible chiral products, 3) chemocatalytic syntheses, and 4) the use of biotechnological methodologies. With respect to the latter one, one can apply enzymatic approaches such as enzymatic resolution (including dynamic kinetic resolution processes) and biocatalytic asymmetric syntheses as well as fermentation. Notably, many of those biotechnological α‐amino acid syntheses have made it up to industrially applied process technologies. The focus of this review is on synthetically widely applied and highly applicable biocatalytic concepts for natural and non‐natural α‐amino acids with one and two stereogenic center(s). Industrial α‐amino acid products as well as their highly efficient process technologies are covered therein as well.
Protein Folding: Energetics
Authors: Baldwin Robert L.
Published: March 2009

The energetics of protein folding determine how the amino acid sequence of a protein is constrained to fold into its correct three‐dimensional structure. Thus, knowledge of the folding energetics is needed to predict protein structure from sequence or to modify sequence and structure by protein engineering. The traditional approach to folding energetics, which emphasizes major factors, is followed here. This article discusses chiefly three major factors: the hydrophobic factor, peptide hydrogen bonds/peptide solvation, and backbone conformational entropy. Auxiliary factors, such as van der Waals interactions, disulfide bonds, salt bridges, and helix propensities, are discussed briefly.
Ribosome, Chemistry of
Authors: Karbstein Katrin
Published: March 2009

Ribosomes are the most complex, ancient, and important RNA‐protein complexes present in every cell. A large body of previous data shows that their function is carefully regulated and quality controlled, which leads to a remarkably low rate of amino‐acid misincorporation. A prerequisite to this exquisitely accurate function is correctly assembled ribosomes. Here, I consider mechanisms that may help in regulating ribosome assembly and in ensuring that ribosomes are faithfully assembled. Evidence for the existence of these mechanisms is then presented based on data in the literature. Future experiments will be required to test the importance of these events in quality control.
HIV
: Small Molecule Approaches
Authors: Vacca Joseph P.
Published: March 2009

The human immunodeficiency retrovirus (HIV), recognized widely as the causative agent of AIDS, was discovered over 25 years ago and is one of the most highly studied viruses of all time. In the 1980s through the mid 1990s, only a few treatment options were available and contracting this virus usually resulted in death. Since the introduction in the mid‐1990s of HAART (Highly Active Anti‐Retroviral Therapy), the disease has become manageable for many people who can tolerate the new drugs (1, 2). This review article will describe the way that the virus works and will highlight the many points of intervention and the small molecules that have been developed to stop the virus from replicating.
Iron–Sulfur Clusters: Properties and Functions
Authors: Noodleman Louis , Pique Michael E. , Roberts Victoria A.
Published: March 2009

Iron–sulfur clusters reside at the active sites of iron–sulfur proteins and are intimately involved in many critical biological functions. The active sites are usually redox active, and the most common functions include simple electron transfer, proton‐coupled electron transfer, and oxidation or reduction of substrates. Some nonredox functions that involve cluster electronic polarization have also been established. The redox active character of iron–sulfur clusters and iron atom lability are also used for essential biological regulatory functions both in bacteria and eukaryotic cells. The versatility of sulfur ligation and iron–sulfur covalency (partial charge transfer) lie at the heart of iron–sulfur cluster functionality. Iron–sulfur proteins are among the most ancient biological catalysts, and iron–sulfur clusters may have had important prebiotic functions as well. In this review, we summarize the wide variety of iron–sulfur catalytic and regulatory functions. We show how many spectroscopic and physical methods contribute to our current understanding of catalytic and regulatory states and energetic pathways. Quantum mechanical [largely density functional theory (DFT)] methods link electronic structures to energetics and spectroscopic data, and provide a unifying framework for additional progress on many open questions. The active site transition metal complexes also interact with the protein and solvent environment. The main theoretical/computational tools for studying these interactions are Poisson‐Boltzmann electrostatics methods and combined quantum mechanics/molecular mechanics (QM/MM) methods. The principal experimental tools for examining cluster‐protein interactions include comparisons of synthetic complexes with corresponding proteins, the use of alternative substrates or inhibitors for enzymes, redox energetics, reaction kinetics studies, and spectroscopic observations.
De Novo Sequencing of Peptides Using Mass Spectrometry
Authors: Dass Chhabil
Published: March 2009

Peptides are important biomolecules that play a variety of functional roles. Knowledge of the specific sequence of amino acids in peptides is essential to understand their biological functions, to identify them in target tissues, to map changes in their metabolic profile, to assess the purity of newly synthesized peptides and to characterize their precursor proteins. Currently, mass spectrometry has assumed a pivotal role in determining the sequence of peptides. The procedure involves conversion of peptide molecules into gas‐phase ions, fragmentation of these species into the sequence‐specific ions, and deciphering the mass spectral data into the sequence of the target peptide. This procedure, known as “
de novo
sequencing”, requires understanding of the peptide fragmentation rules and guidelines for interpretation of a mass spectrum. These aspects are discussed in detail in this chapter.
The $300,000/Year Architect
Authors: Gauchet Urs
Published: March 2009

Could building information modelling (BIM) shake up not only design and delivery processes, but also be set to redefine the construction hierarchy? Could it shift the architect's position from near the bottom of the current food chain to one nearer the top? Urs Gauchat, Professor and Dean of the School of Architecture at the New Jersey Institute of Technology, outlines the architect's place in a complex future where there is an increasing demand for buildings but a demise in available materials and conventional energy sources. Copyright © 2009 John Wiley & Sons, Ltd.
Information Modelling as a Paradigm Shift
Authors: Shelden Dennis
Published: March 2009

Building information modelling (BIM) is not just a change in software or skills sets, it requires a paradigm shift. Dennis Shelden, Chief Technology Officer of Gehry Technologies, outlines the more ‘fundamental, subtle and profound decisions’ on the road to BIM. It is necessary to fully consider not only the impacts both ‘upstream’ and ‘downstream’ from the conventional design phase, but also the possible creative restrictions as there is a potential trade‐off that comes with the emphasis on collaborative processes. Copyright © 2009 John Wiley & Sons, Ltd.
Carlos Zapata and Antonio Citterio's Cooper Square Hotel, New York
Authors: Merkel Jayne
Published: March 2009

Unlike most glamorous new high‐rise apartment buildings in downtown Manhattan, this thin, tilted white glass tower provides homes away from home for chic out‐of‐towners. And what ‘homes’ they are. Upstairs are astounding long‐range views; on the lower floors, a series of glass‐walled lounges, restaurants, balconies, a garden and even a library with a wood‐burning fireplace. And, as Jayne Merkel explains, these sensual pleasures are mixed with intellectual ones. There are art and travel books in every room and guests can enjoy ‘movie nights’ in the screening room.
Herbert Art Gallery and Museum, Coventry
Authors: Littlefield David
Published: March 2009

Despite being ‘assembled from fragments’, like the Midlands city in which it is located, the new extension to the Herbert Art Gallery provides a new refinement and logic to the previously eclectic museum and its environs. David Littlefield describes how Pringle Richards Sharratt have realised this new coherency through artful layering, reorientation and rationalisation. Copyright © 2009 John Wiley & Sons, Ltd.
Computational Spring Systems: Open Design Processes for Complex Structural Systems
Authors: Ahlquist Sean , Fleischmann Moritz
Published: March 2009

Sean Ahlquist and Moritz Fleischmann are both former graduates of the Emergent Technologies and Design Programme at the Architectural Association (AA) in London, who have now established their own innovative research and design practice, morse. Here they describe their work with computational spring algorithms that has enabled iterative investigations of tension active systems and structures. Copyright © 2009 John Wiley & Sons, Ltd.
Complex Systems Architecture
Authors: Spiller Neil
Published: March 2009

Neil Spiller reveals the complexity of architectural systems to us, or is it the complexity of the architectural mind? For Spiller, the potential of a single notation as a seed for a truly ecological architecture provides an essential catalyst, triggering a multifaceted musing that takes in diagrams, Paul Preissner's new competition entry for the Taiwan Centre of Disease Control and his future work with Dr Rachel Armstrong on complex biological systems. Copyright © 2009 John Wiley & Sons, Ltd.
The Sustainable Disco
Authors: Croci Valentina
Published: March 2009

Valentina Croci describes how Dutch artist Daan Roosegaarde's Sustainable Dance Floor (SDF) provides the centrepiece for an eco‐club in Rotterdam that builds low energy consumption into the attraction. The square dance floor uses ‘mechatronic’ sensors to convert kinetic movement into electricity when people dance. Movement is not only part of the thrill, but is literally electrifying. Copyright © 2009 John Wiley & Sons, Ltd.
Replacing a Beloved Building with a Hybrid: Paresky Student Center, Williams College
Authors: Horwitz Jamie
Published: March 2009

Jamie Horwitz describes how Polshek Partnership's design for a new student centre at Williams College, a small liberal arts college in Williamstown, Massachusetts, has successfully integrated ‘environmentally sensitive practices into the choreography of life’. Catering not only to students' 24‐hour needs, its dining facilities tap into a network of local food producers within its far‐reaching sustainable programme. Copyright © 2009 John Wiley & Sons, Ltd.
Intercalating Dye Harnessed Cationic Conjugated Polymer for Real‐Time Naked‐Eye Recognition of Double‐Stranded DNA in Serum
Authors: Pu Kan‐Yi , Liu Bin
Published: March 2009

Thiazole orange (TO), an intercalating dye, is integrated into cationic poly(fluorene‐alt‐phenylene) (PFP) to develop a macromolecular multicolor probe (PFPTO) for double‐stranded DNA (dsDNA) detection. This polymer design not only takes advantage of the high affinity between TO and dsDNA to realize dsDNA recognition in biological media, but also brings into play the light‐harvesting feature of conjugated polymers to amplify the signal output of TO in situ. PFPTO differentiates dsDNA from single‐stranded DNA (ssDNA) more effectively upon excitation of the conjugated backbone relative to that upon direct excitation of TO as a result of efficient fluorescence resonance energy transfer from the polymer backbone to the intercalated TO. In the presence of dsDNA, energy transfer within PFPTO is more efficient as compared to that for free TO/PFP system, which leads to better dsDNA discriminability for PFPTO in contrast to that for TO/PFP. The distinguishable fluorescent color for PFPTO solutions in the presence of dsDNA allows naked‐eye detection of dsDNA with the assistance of a hand‐held UV lamp. The significant advantage of this macromolecular fluorescent probe is that naked‐eye detection of label‐free dsDNA can be performed in biological media in real‐time.
Labeling of Adipose‐Derived Stem Cells by Oleic‐Acid‐Modified Magnetic Nanoparticles
Authors: Cen Lian , Neoh Koon Gee , Sun Jian , Hu Feixiong , Liu Wei , Cui Lei , Cao Yilin
Published: March 2009

The in vivo tracking of adipose derived stem cells (ASCs) is of essential concern when they are used as seed cells in tissue engineering. This study explores the feasibility of using magnetic nanoparticles (MNs), a type of contrast agents in magnetic resonance imaging (MRI), to label ASCs such that the labeled ASCs could be tracked in vivo by MRI non‐invasively and repeatedly. To do this, MNs of <10 nm surface‐coated with oleic acid are synthesized via a high‐temperature solution‐phase reaction. Cytotoxicity of the as‐synthesized MNs at concentrations up to 0.1 mg mL−1 on 104 cells mL−1 ASCs is evaluated by LDH release. Since only minor cytotoxicity is detected, the effects of the labeling technique on cellular behaviors and uptake by labeled cells are investigated. Cell proliferation and differentiation with and without MNs are compared. The results show that proliferation of ASCs (104 cells mL−1) labeled by MNs (0.05 mg mL−1) is significantly enhanced and dependent on the labeling time. The MNs are located in the vesicles within cytoplasm of ASCs. The cellular uptake reaches as high as ∼180 pg/cell. Nevertheless, the labeled ASCs still maintained adipogenic and osteogenic differentiation. Hence, the feasibility of labeling ASCs by oleic acid coated MNs is ascertained and it was better to label the cells during their quiescent stage. The labeled ASCs can also be in vivo detected by MRI in a subcutaneous model in vivo. Further MRI tracking of the labeled ASCs in long‐term follow‐up would thus follow this current study.
Exposure to hazardous workplace noise and use of hearing protection devices among US workers—NHANES, 1999–2004
Authors: Tak SangWoo , Davis Rickie R. , Calvert Geoffrey M.
Published: March 2009

Background

To estimate the prevalence of workplace noise exposure and use of hearing protection devices (HPDs) at noisy work, NIOSH analyzed 1999–2004 data from the National Health and Nutrition Examination Survey (NHANES).

Methods

A total of 9,275 currently employed workers aged ≥16 years were included in the weighted analysis. Hazardous workplace noise exposure was defined as self‐reported exposure to noise at their current job that was so loud that the respondent had to speak in a raised voice to be heard. Industry and occupation were determined based on the respondent's current place and type of work.

Results

Twenty‐two million US workers (17%) reported exposure to hazardous workplace noise. The weighted prevalence of workplace noise exposure was highest for mining (76%, SE = 7.0) followed by lumber/wood product manufacturing (55%, SE = 2.5). High‐risk occupations included repair and maintenance, motor vehicle operators, and construction trades. Overall, 34% of the estimated 22 million US workers reporting hazardous workplace exposure reported non‐use of HPDs. The proportion of noise‐exposed workers who reported non‐use of HPDs was highest for healthcare and social services (73.7%, SE = 8.1), followed by educational services (55.5%).

Discussion

Hearing loss prevention and intervention programs should be targeted at those industries and occupations identified to have a high prevalence of workplace noise exposure and those industries with the highest proportion of noise‐exposed workers who reported non‐use of HPDs. Am. J. Ind. Med. 52:358–371, 2009. Published 2009 Wiley‐Liss, Inc.
Prosaposin deficiency and saposin B deficiency (activator‐deficient metachromatic leukodystrophy): Report on two patients detected by analysis of urinary sphingolipids and carrying novel PSAP gene mutations
Authors: Kuchař Ladislav , Ledvinová Jana , Hřebíček Martin , Myšková Helena , Dvořáková Lenka , Berná Linda , Chrastina Petr , Asfaw Befekadu , Elleder Milan , Petermöller Margret , Mayrhofer Heidi , Staudt Martin , Krägeloh‐Mann Ingeborg , Paton Barbara C. , Harzer Klaus
Published: March 2009

Prosaposin deficiency (pSap‐d) and saposin B deficiency (SapB‐d) are both lipid storage disorders caused by mutations in the PSAP gene that codes for the 65–70 kDa prosaposin protein, which is the precursor for four sphingolipid activator proteins, saposins A–D. We report on two new patients with PSAP gene defects; one, with pSap‐d, who had a severe neurovisceral dystrophy and died as a neonate, and the other with SapB‐d, who presented with a metachromatic leukodystrophy‐like disorder but had normal arylsulfatase activity. Screening for urinary sphingolipids was crucial to the diagnosis of both patients, with electrospray ionization tandem mass spectrometry also providing quantification. The pSap‐d patient is the first case with this condition where urinary sphingolipids have been investigated. Multiple sphingolipids were elevated, with globotriaosylceramide showing the greatest increase. Both patients had novel mutations in the PSAP gene. The pSap‐d patient was homozygous for a splice‐acceptor site mutation two bases upstream of exon 10. This mutation led to a premature stop codon and yielded low levels of transcript. The SapB‐d patient was a compound heterozygote with a splice‐acceptor site variant exclusively affecting the SapB domain on one allele, and a 2 bp deletion leading to a null, that is, pSap‐d mutation, on the other allele. Phenotypically, pSap‐d is a relatively uniform disease of the neonate, whereas SapB‐d is heterogeneous with a spectrum similar to that in metachromatic leukodystrophy. The possible existence of genotypes and phenotypes intermediate between those of pSap‐d and the single saposin deficiencies is speculated. © 2009 Wiley‐Liss, Inc.
The c.940G variant of the Microcephalin (MCPH1) gene is not associated with microcephaly or mental retardation
Authors: Maghirang‐Rodriguez Reycel , Archie John G. , Schwartz Charles E. , Collins Julianne S.
Published: March 2009

It was reported that positive selection has acted upon a gene involved in autosomal recessive primary microcephaly, Microcephalin (MCPH1/BRIT1), located at chromosome 8p23. We tested if the reported diagnostic single nucleotide polymorphism (SNP) (G37995C or c.940G > C) of a derived haplogroup of the MCPH1 gene had significantly different frequencies in mental retardation (MR) patients and in MR patients with microcephaly as compared to MR patients without microcephaly and controls in African‐American and Caucasian populations in South Carolina, US. Our results suggest that there is little or no association between the MCPH1 c.940G allele and either microcephaly or MR. However, we found highly significant racial differences in the c.940G > C SNP allele frequencies between African‐American and Caucasian populations. © 2009 Wiley‐Liss, Inc.
What role do olfactory cues play in chacma baboon mating?
Authors: Clarke Parry M. R. , Barrett L. , Henzi S. P.
Published: March 2009

The probability of ovulation in a number of primate species is associated with both visual and auditory cues. We use 18‐month behavioral data from two chacma baboon troops to provide the first systematic assessment of the possibility that olfactory cues are also involved. Using variance in the rate of olfactory inspection by males as a proxy for changes in the intensity of female vaginal odor, we found that rates of inspection were broadly correlated with changes in female fertility. Males inspected cycling females significantly more than anovulatory, noncycling females and swelling females significantly more than nonswollen cycling females. Rates of inspection peaked around the time at which males first started guarding females and were sustained until the detumescence of the female's sexual skin. We conclude, therefore, that olfactory cues represent one component of a multimodal signal of ovulation in chacma baboons. The possible reasons for such a multimodal signal are discussed. Am. J. Primatol. 71:493–502, 2009. © 2009 Wiley‐Liss, Inc.
Electrodeposition of 3D Ordered Macroporous Germanium from Ionic Liquids: A Feasible Method to Make Photonic Crystals with a High Dielectric Constant
Authors: Meng Xiangdong , Al‐Salman Rihab , Zhao Jiupeng , Borissenko Natalia , Li Yao , Endres Frank
Published: March 2009

A promising method for the production of germanium photonic crystals consists of electrodeposition of Ge from GeCl4‐containing ionic liquids inside templates of polystyrene colloidal crystals and subsequent removal of the template. This room‐temperature method gives rise to the fabrication of a three‐dimensional highly ordered macroporous germanium nanostructure (see picture; scale: 2 μm) as a prototype of a photonic crystal.

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Synthesis of 1,3‐Diamines Through Rhodium‐Catalyzed CH Insertion
Authors: Kurokawa Toshiki , Kim Mihyong , Du Bois J.
Published: March 2009

A grand opening: N‐Boc‐N‐alkylsulfamides are effective substrates for the title transformation. Oxidative cyclization is highly chemoselective as well as being both stereospecific and diastereoselective. With the advent of new protocols that facilitate ring opening of the six‐membered‐ring heterocyclic products, access to differentially protected 1,3‐diamines has been made possible (see scheme).

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Investigation of the interpolymer association between poly(vinyl alcohol) and poly(sodium styrene sulfonate) in aqueous solution
Authors: Mbareck Chamekh , Nguyen Q. T.
Published: March 2009

A viscosimetric method has been used to study the interpolymer association between poly(vinyl alcohol) (PVA) and poly(sodium styrene sulfonate) (PSSNa) in aqueous solution. At constant molecular weight of PSSNa, it was found that, the PVA and PSSNa associations were improved with the decrease of molecular weight of PVA and the decrease of its hydrolysis degree. The measurement of intrinsic viscosity [η] and the determination of Huggins associative coefficient KH of different PVA samples were used to select the most appropriate PVA sample, which leads to homogeneous polymer–polymer mixtures (PVA with hydrolysis degree 87–89%, molecular weight 124,000–186,000 g/mol, intrinsic viscosity [η] = 1.02 dL/g, and Huggins associative coefficient Kh.ass = 0.76). The obtained results show that the interpolymer association between PVA and PSSNa, in aqueous solution, is mainly due to intermolecular hydrogen bonds between hydroxyl groups of PVA and sulfonate groups of PSSNa. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Transferring polypropylene into carbon nanotubes via combustion of PP/zeolites (H‐ZSM‐5 or H‐beta)/Ni2O3
Authors: Song Rongjun , Li Bin , Zhao Shu , Li Liping
Published: March 2009

In a simple device, two kinds of zeolites were successfully used as synergistic additive to promote formation of the multi‐walled carbon nanotubes (MWNTs) from polypropylene (PP) via combustion. More importantly, this kind of process may potentially act as a new approach for recycling plastic wastes, because it could effectively transfer polyolefin wastes into valuable carbon materials. Experimental results demonstrated that the higher quality of MWNTs can be obtained from the mixture (PP/H‐Beta/Ni2O3) than that from the mixture (PP/H‐ZSM‐5/Ni2O3). At the same time, the yield of MWNTs from PP/H‐ZSM‐5/Ni2O3 system is much lower than that from PP/H‐Beta/Ni2O3 under the same condition. The reason for the different effects of both types of zeolites on the morphology and the yield of the MWNTs was analyzed. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Mechanical properties and biomass carbon ratios of poly(butylene succinate) composites filled with starch and cellulose filler using furfural as plasticizer
Authors: Flores E. D. , Funabashi M. , Kunioka M.
Published: March 2009

Polymer composites consisting of poly(butylene succinate) (PBS) as matrix and corn starch (CS) or cellulose filler (CF) with a small amount of furfural (FR) from biomass were prepared by a hot‐pressing method at 120°C from a powder mixture. Mechanical properties of the composites' films were investigated using tensile test methods. The strain of these films was found to be developed by adding CS or CF and further improved by adding FR. The strain at break PBS with 15 wt % FR was improved by more than 16 times of that of PBS without FR. The biomass carbon ratios of polymer composites with oil‐based PBS (major component) and with biobased CS, CF, and FR were evaluated by 14C concentration ratio measured by accelerator mass spectrometry (AMS) based on ASTM D6866. PBS with 40 wt % CS or CF had a biomass carbon ratio of 31 and 36%, respectively. PBS with 15 wt % FR had a biomass carbon ratio of 3.4%. This deviation was confirmed by FR content calculated from the peak area of the 1H‐NMR spectrum of PBS with FR which was 3.4%, almost the same as the biomass carbon ratio measured by AMS. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Strontium aluminate/polymer composites: Morphology, luminescent properties, and durability
Authors: Mishra S. B. , Mishra A. K. , Revaprasadu N. , Hillie K. T. , Steyn W. J. vdM. , Coetsee E. , Swart H. C.
Published: March 2009

Phosphor‐based polymer composites were prepared using a melt mixing and extrusion method. Morphology, luminescent properties, and Hamburg wheel test (HWT) of synthesized hybrid material were studied using various polymer matrices. The intensities of the luminescence of the strontium aluminates phosphors (SrAl2O4 : Eu,Dy and Sr4Al14O25 : Eu,Dy) were substantially changed when incorporated into structurally and chemically different organic matrices. HWTs were performed to evaluate the durability of the polymers against simulated wheel loads and the effect of these wheel loads on the luminosity of the polymers. The decay slopes of various polymer–phosphor composites suggests that the simulated wheel load of the Hamburg test did not have a profound effect on the luminosity as such but the duration of luminescence was found to be shorter for the polymer–phosphor hybrid after the Hamburg test. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Short‐range urban dispersion experiments using fixed and moving sources
Authors: Shallcross D. E. , Martin D. , Price C. S. , Nickless G. , White I. R. , Petersson F. , Britter R. E. , Neophytou M. K. , Tate J. E. , Tomlin A. S. , Belcher S. E. , Barlow J. F. , Robins A.
Published: March 2009

Four perfluorocarbon tracer dispersion experiments were carried out in central London, United Kingdom in 2004. These experiments were supplementary to the dispersion of air pollution and penetration into the local environment (DAPPLE) campaign and consisted of ground level releases, roof level releases and mobile releases; the latter are believed to be the first such experiments to be undertaken. A detailed description of the experiments including release, sampling, analysis and wind observations is given. The characteristics of dispersion from the fixed and mobile sources are discussed and contrasted, in particular, the decay in concentration levels away from the source location and the additional variability that results from the non‐uniformity of vehicle speed. Copyright © 2009 Royal Meteorological Society