bluuebunny/crossref_metadata_2025 huggingface dataset:
SOCS-1 Binding to Tyrosine 441 of IFN-γ Receptor Subunit 1 Contributes to the Attenuation of IFN-γ Signaling In Vivo
Authors: Starr Robyn , Fuchsberger Martina , Lau Lei Shong , Uldrich Adam P. , Goradia Ankita , Willson Tracy A. , Verhagen Anne M. , Alexander Warren S. , Smyth Mark J.
Published: September 2009

Suppressor of cytokine signaling (SOCS)-1 is a critical inhibitor of IFN-γ signal transduction in vivo, but the precise biochemical mechanism of action of SOCS-1 is unclear. Studies in vitro have shown that SOCS-1 binds to Jaks and inhibits their catalytic activity, but recent studies indicate SOCS-1 may act in a similar manner to SOCS-3 by firstly interacting with cytokine receptors and then inhibiting Jak activity. Here, we have generated mice, termed Ifngr1441F, in which a putative SOCS-1 binding site, tyrosine 441 (Y441), on the IFN-γ receptor subunit 1 (IFNGR1) is mutated. We confirm that SOCS-1 binds to IFNGR1 in wild-type but not mutant cells. Mutation of Y441 results in impaired negative regulation of IFN-γ signaling. IFN-γ-induced STAT1 activation is prolonged in Ifngr1441F cells, but not to the extent seen in cells completely lacking SOCS-1, suggesting that SOCS-1 maintains activity to modulate IFN-γ signaling via other mechanisms. Despite this, we show that hypersensitivity to IFN-γ results in enhanced innate tumor protection in Ifngr1441F mice in vivo, and unregulated expression of an IFN-γ–dependent chemokine, monokine-induced by IFN-γ. Collectively, these data indicate that Y441 contributes to the regulation of signaling through IFNGR1 via the recruitment of SOCS-1 to the receptor.
Invariant TCR Rather Than CD1d Shapes the Preferential Activities of C-Glycoside Analogues Against Human Versus Murine Invariant NKT Cells
Authors: Li Xiangming , Shiratsuchi Takayuki , Chen Guangwu , Dellabona Paolo , Casorati Giulia , Franck Richard W. , Tsuji Moriya
Published: September 2009

C-glycoside analogues of α-galactosylceramide were shown to activate both human and mouse invariant NKT (iNKT) cells. Among these analogues, GCK152, which has an aromatic ring in the acyl chain, exhibited a stronger stimulatory activity against human iNKT cells and a much weaker activity against murine iNKT cells than GCK127 that has an almost identical fatty acyl chain as α-galactosylceramide. In this study, we have found that invariant TCR (invTCR) expressed by iNKT cells, but not CD1d expressed by APCs, command the species-specific preferential activity of C-glycosides, and that their preferential activity against human vs murine iNKT cells correlate with the binding affinity of glycolipid-CD1d complex to invTCR of respective iNKT cells rather than that of glycolipid to human or murine CD1d molecules. Overall, the structural difference of invTCR appears to supersede those of CD1d molecule in shaping the strength of the biological activity of C-glycoside analogues.
Reciprocal Human Dendritic Cell–Natural Killer Cell Interactions Induce Antitumor Activity Following Tumor Cell Infection by Oncolytic Reovirus
Authors: Prestwich Robin J. , Errington Fiona , Steele Lynette P. , Ilett Elizabeth J. , Morgan Ruth S. M. , Harrington Kevin J. , Pandha Hardev S. , Selby Peter J. , Vile Richard G. , Melcher Alan A.
Published: September 2009

Oncolytic virotherapy may mediate antitumor effects via direct oncolysis or immune-mediated tumor regression. Although the ability of oncolytic viruses to generate adaptive antitumor immunity has been characterized, their interactions with the innate immune system are relatively unclear. Using a human in vitro system, this study investigates the innate immunological consequences of reovirus therapy and its potential to activate NK cell-mediated antitumor activity. Dendritic cells (DC) loaded with reovirus-infected human melanoma Mel888 cells (DC-MelReo), but not reovirus-infected tumor cells alone, induced IFN-γ production within the NK cell population upon coculture with PBMC, in a cell-to-cell contact-dependent manner. DC-MelReo secreted the chemokines CCL2, 3, 4, 5, 7, 8, 11, and CXCL10; these culture supernatants induced NK cell chemotaxis. Coculture of DC-MelReo with purified NK cells induced reciprocal contact-dependent phenotypic DC maturation, while DC-MelReo elicited up-regulation of the activation marker CD69 on NK cells, in a partially contact and partially IL-12 dependent manner. Significantly, DC-MelReo induced NK cell cytotoxicity toward tumor cells by a type I IFN dependent mechanism. These data demonstrate that tumor infection by reovirus can act via DC to induce NK cell recruitment, activation, and cytotoxicity, along with reciprocal DC maturation. These findings suggest that reciprocal DC-NK cell interactions, following reovirus therapy, may play an important role in altering the immune milieu of the tumor microenvironment and mediating tumor regression.
Dynamic Development of Homing Receptor Expression and Memory Cell Differentiation of Infant CD4+CD25high Regulatory T Cells
Authors: Grindebacke Hanna , Stenstad Hanna , Quiding-Järbrink Marianne , Waldenström Jesper , Adlerberth Ingegerd , Wold Agnes E. , Rudin Anna
Published: September 2009

Migration of CD4+CD25+FOXP3+ regulatory T cells (Treg) is important for suppressing immune responses in different tissues. Previous studies show that the majority of Treg at birth express gut homing receptor α4β7 and that only few express CCR4, while the reverse pattern is found in adults. The age at which homing receptor switch occurs in vivo is not known. In this study, we show, in a prospective study of human infants from birth to 3 years of age, that homing receptor switch from α4β7 to CCR4 commences between 1 1/2 and 3 years of age and that Treg at that age also had started their switch to a memory phenotype. The majority of naive Treg express α4β7 in infants but not in adults, while the majority of memory Treg express CCR4 both infants and adults. The homing receptor expression on Treg corresponds to their actual migration properties, because Treg from cord blood migrate foremost toward the gut-associated chemokine CCL25. CD4+FOXP3+ T cell numbers increase rapidly in the circulation during the first days of life indicating conversion to suppressive Treg from CD25high Treg precursors. These findings suggest that the gut is the primary site of Treg stimulation to exogenous Ags during the first 18 mo of life and that homing receptor switch toward a more extra-intestinal phenotype occurs thereafter.
The Proinflammatory Action of Microglial P2 Receptors Is Enhanced in SOD1 Models for Amyotrophic Lateral Sclerosis
Authors: D'Ambrosi Nadia , Finocchi Pamela , Apolloni Savina , Cozzolino Mauro , Ferri Alberto , Padovano Valeria , Pietrini Grazia , Carrì Maria Teresa , Volonté Cinzia
Published: September 2009

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective loss of lower and upper motoneurons. The pathology is imputable in ∼2% of cases to mutations in the ubiquitous enzyme Cu, Zn superoxide dismutase (SOD1). Common theories to explain the pathogenic mechanisms of ALS include activation of microglia, responsible for the release of proinflammatory factors. However, how mutant SOD1 affects microglial activation and subsequently injures neurons is still unclear. Considering that extracellular ATP, through purinergic P2 receptors, constitutes a well recognized neuron-to-microglia alarm signal, the aim of this study was to investigate how the expression of mutant SOD1 affects P2 receptor-mediated proinflammatory microglial properties. We used primary and immortalized microglial cells from mutant SOD1 mice to explore several aspects of activation by purinergic ligands and to analyze the overall effect of such stimulation on the viability of NSC-34 and SH-SY5Y neuronal cell lines. We observed up-regulation of P2X4, P2X7, and P2Y6 receptors and down-regulation of ATP-hydrolyzing activities in mutant SOD1 microglia. This potentiation of the purinergic machinery reflected into enhanced sensitivity mainly to 2′-3′-O-(benzoyl-benzoyl) ATP, a P2X7 receptor preferential agonist, and translated into deeper morphological changes, enhancement of TNF-α and cyclooxygenase-2 content, and finally into toxic effects exerted on neuronal cell lines by microglia expressing mutant SOD1. All these parameters were prevented by the antagonist Brilliant Blue G. The purinergic activation of microglia may thus constitute a new route involved in the progression of ALS to be exploited to potentially halt the disease.
Differentiation-Associated Loss of Ryanodine Receptors: A Strategy Adopted by Monocytes/Macrophages to Prevent the DNA Single-Strand Breakage Induced by Peroxynitrite
Authors: Guidarelli Andrea , Cerioni Liana , Fiorani Mara , Cantoni Orazio
Published: September 2009

Monocytes/macrophages respond to peroxynitrite with the triggering of events leading to prevention of an otherwise prompt lethal response. This survival signaling regulated by molecules of the arachidonate cascade however presents a hypothetical critical limitation. In human promonocytic cell lines, peroxynitrite indeed promotes ryanodine receptor-derived Ca2+-dependent mitochondrial formation of H2O2, entirely responsible for the ensuing DNA strand scission. The occurrence of the same events in monocytes/macrophages at the inflammatory sites would therefore enhance the extent of DNA strand scission in viable cells, thereby increasing the rate of mutation and neoplastic transformation. The present study illustrates the details of a novel strategy based on a differentiation-associated loss of expression of ryanodine receptors. These cells simply do not accumulate mitochondrial Ca2+ in response to peroxynitrite and therefore fail to generate superoxide/H2O2, thereby preserving the integrity of their DNA. We propose that an important component of the overall strategy adopted by monocytes/macrophages to survive to peroxynitrite, with no increased risk of neoplastic transformation, involves down-regulation of ryanodine receptor expression.
c-Jun Controls the Ability of IL-12 to Induce IL-10 Production from Human Memory CD4+ T Cells
Authors: Garcia Carlos A. , Wang Huizhi , Benakanakere Manjunatha R. , Barrett Elyse , Kinane Denis F. , Martin Michael
Published: September 2009

IL-12p70 is an immunoregulatory cytokine that has been shown to induce IL-10 production from CD4+ T cells, yet the underlying cellular mechanisms controlling this process are poorly understood. In the present study, we demonstrate that IL-12p70 induces IL-10 production from human memory CD4+ T cells via a PI3K-dependent signaling mechanism. Specifically, stimulation of human memory CD4+ T cells in the presence of IL-12p70 lead to increased PI3K activity and the subsequent phosphorylation and inactivation of the downstream constitutively active serine/threonine kinase, glycogen synthase kinase-3β (GSK3β). Inhibition of PI3K prevented the inactivation of GSK3β by IL-12p70, as well as the subsequent ability of IL-12p70 to augment IL-10 levels by memory CD4+ T cells. Moreover, ectopic expression of a constitutively active form of GSK3β abrogated the ability of IL-12p70 to increase IL-10 production by TCR-stimulated CD4+ T cells. In contrast, direct inhibition of GSK3 mimicked the effect of IL-12p70 on IL-10 production by memory CD4+ T cells. Analysis of downstream transcription factors identified that the ability of IL-12p70 to inactivate GSK3β lead to increased levels of c-Jun. The ability of IL-12p70 to inactivate GSK3β and induce c-Jun levels was required for IL-12 to augment IL-10 production by human memory CD4+ T cells, since small interfering RNA-mediated gene silencing of c-Jun abrogated this process. These studies identify the cellular mechanism by which IL-12 induces IL-10 production from human memory CD4+ T cells.
Reviving Function in CD4+ T Cells Adapted to Persistent Systemic Antigen
Authors: Rivas Magali Noval , Weatherly Kathleen , Hazzan Marc , Vokaer Benoit , Dremier Sarah , Gaudray Florence , Goldman Michel , Salmon Isabelle , Braun Michel Y.
Published: September 2009

In bone marrow-transplanted patients, chronic graft-versus-host disease is a complication that results from the persistent stimulation of recipient minor histocompatibility Ag (mHA)-specific T cells contained within the graft. In this study, we developed a mouse model where persistent stimulation of donor T cells by recipient’s mHA led to multiorgan T cell infiltration. Exposure to systemic mHA, however, deeply modified T cell function and chronically stimulated T cells developed a long-lasting state of unresponsiveness, or immune adaptation, characterized by their inability to mediate organ immune damages in vivo. However, analysis of the gene expression profile of adapted CD4+ T cells revealed the specific coexpression of genes known to promote differentiation and function of Th1 effector cells as well as genes coding for proteins that control T cell activity, such as cell surface-negative costimulatory molecules and regulatory cytokines. Strikingly, blockade of negative costimulation abolished T cell adaptation and stimulated strong IFN-γ production and severe multiorgan wasting disease. Negative costimulation was also shown to control lethal LPS-induced toxic shock in mice with adapted T cells, as well as the capacity of adapted T cells to reject skin graft. Our results demonstrate that negative costimulation is the molecular mechanism used by CD4+ T cells to adapt their activity in response to persistent antigenic stimulation. The effector function of CD4+ T cells that have adapted to chronic Ag presentation can be activated by stimuli strong enough to overcome regulatory signals delivered to the T cells by negative costimulation.
ThPOK Derepression Is Required for Robust CD8 T cell Responses to Viral Infection
Authors: Setoguchi Ruka , Taniuchi Ichiro , Bevan Michael J.
Published: September 2009

In the thymus, the transcription factor ThPOK is essential for the development of the CD4 helper T cell lineage, whereas active repression of ThPOK is critical for the development of the CD8 cytotoxic T cell lineage. ThPOK gene silencing is thought to be irreversible in peripheral CD8 T cells. We noticed that ThPOK repression is readily abrogated upon in vitro TCR stimulation of peripheral CD8 T cells. This observation prompted us to investigate a role for ThPOK in the CD8 T cell response to an acute viral infection. We observed that a functional deficiency of ThPOK does not affect CD8 T cell differentiation into effector T cells and the long-term persistence of Ag-specific memory T cells. However, in the absence of functional ThPOK, clonal expansion is significantly less in both primary and secondary CD8 T cell responses. Long-lived, Ag-specific CD8 T cells with a functional deficiency in ThPOK fail to produce high amounts of IL-2 and also fail to express high levels of granzyme B upon rechallenge. Our data reveal an unexpected role for ThPOK in CD8 T cells in promoting expansion and boosting the response to antigenic challenge.
Phosphorothioate-Modified TLR9 Ligands Protect Cancer Cells against TRAIL-Induced Apoptosis
Authors: Chiron David , Pellat-Deceunynck Catherine , Maillasson Mike , Bataille Régis , Jego Gaëtan
Published: September 2009

Hypomethylated CpG oligodeoxynucleotides (CpG ODNs) target TLR9 expressed by immune cells and are currently being evaluated as adjuvants in clinical trials. However, TLR signaling can promote some tumor growth and immune evasion, such as in multiple myeloma (MM). Therefore, deciphering the effects of CpG ODNs on cancer cells will help in preventing these adverse effects and in designing future clinical trials. TLR activation induces multiple signaling pathways, notably NF-κB that has been involved in the resistance to TRAIL. Thus, we wondered if CpG ODNs could modulate TRAIL-induced apoptosis in different models of tumors. Here, we show that TLR9+ (NCI-H929, NAN6, KMM1) and TLR9− MM cells (MM1S) were protected by CpG ODNs against recombinant TRAIL-induced apoptosis. By using two fully human, agonist mAbs directed against TRAIL receptors DR4 and DR5 (mapatumumab and lexatumumab, respectively), we show that the protection was restricted to DR5-induced apoptosis. Similar results were observed for two colon cancer (C45 and Colo205) and two breast cancer cell lines (HCC1569 and Cal51). The protection of CpG ODNs was mediated by its nuclease-resistant phosphorothioate backbone independent of TLR9. We next demonstrated by surface plasmon resonance that phosphorothioate-modified CpG ODNs directly bound to either TRAIL or lexatumumab and then decreased their binding to DR5. Finally, NK cell lysis of a DR5-sensitive MM cell line (NCI-H929) through TRAIL was partially inhibited by phosphorothioate-modified CpG ODNs. In conclusion, our results suggest that the phosphorothioate modification of CpG ODNs could dampen the clinical efficacy of CpG ODN-based adjuvants by altering TRAIL/TRAIL receptor interaction.
Human TCR-αβ+ CD4− CD8− T Cells Can Derive from CD8+ T Cells and Display an Inflammatory Effector Phenotype
Authors: Crispín José C. , Tsokos George C.
Published: September 2009

The origin and function of human double negative (DN) TCR-αβ+ T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. In this study, we provide evidence that human TCR-αβ+ CD4− CD8− DN T cells can derive from activated CD8+ T cells. Freshly isolated TCR-αβ+ DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8+ T cells produce a defined array of proinflammatory mediators that includes IL-1β, IL-17, IFN-γ, CXCL3, and CXCL2. These results indicate that, upon activation, CD8+ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity.
Quantitating T Cell Cross-Reactivity for Unrelated Peptide Antigens
Authors: Ishizuka Jeffrey , Grebe Kristie , Shenderov Eugene , Peters Bjoern , Chen Qiongyu , Peng YanChun , Wang Lili , Dong Tao , Pasquetto Valerie , Oseroff Carla , Sidney John , Hickman Heather , Cerundolo Vincenzo , Sette Alessandro , Bennink Jack R. , McMichael Andrew , Yewdell Jonathan W.
Published: September 2009

Quantitating the frequency of T cell cross-reactivity to unrelated peptides is essential to understanding T cell responses in infectious and autoimmune diseases. Here we used 15 mouse or human CD8+ T cell clones (11 antiviral, 4 anti-self) in conjunction with a large library of defined synthetic peptides to examine nearly 30,000 TCR-peptide MHC class I interactions for cross-reactions. We identified a single cross-reaction consisting of an anti-self TCR recognizing a poxvirus peptide at relatively low sensitivity. We failed to identify any cross-reactions between the synthetic peptides in the panel and polyclonal CD8+ T cells raised to viral or alloantigens. These findings provide the best estimate to date of the frequency of T cell cross-reactivity to unrelated peptides (∼1/30,000), explaining why cross-reactions between unrelated pathogens are infrequently encountered and providing a critical parameter for understanding the scope of self-tolerance.
Negative Regulation of MAVS-Mediated Innate Immune Response by PSMA7
Authors: Jia Yongxia , Song Ting , Wei Congwen , Ni Caifei , Zheng Zirui , Xu Quanbin , Ma Hongfang , Li Li , Zhang Yanhong , He Xiang , Xu Yang , Shi Wei , Zhong Hui
Published: September 2009

Innate immunity to viruses involves receptors such as Retinoic Acid Induced Gene-1 (RIG-I), which senses viral RNA and triggers a signaling pathway involving the outer mitochondrial membrane protein mitochondrial antiviral signaling (MAVS). Recent work has identified that NLRX1, a member of another class of innate immune receptors, sequesters MAVS away from RIG-I and thereby prevents mitochondrial antiviral immunity. In this study, we demonstrate that the proteasome PSMA7 (α4) subunit associates with MAVS in vivo and in vitro. Expression of PSMA7 results in a potent inhibition of RIG-1 and MAVS-mediated IFN-β promoter activity; conversely, depletion of PSMA7 with small interference RNA enhances virus-induced type I IFN production, with consequent reduction of virus replication. Furthermore, a striking reduction in the abundance of endogenous MAVS with overexpressed PSMA7 was found and virus infection leads to transient increase in the endogenous PSMA7 protein level. Cumulatively, these results suggest that PSMA7 is a negative regulator of the MAVS-mediated innate immunity that probably serves to attenuate the establishment of an antiviral state during viral infection, highlighting the biological significance of PSMA7-MAVS association as an important cellular regulatory control.
Innate Immunity against Bacterial Infection following Hyperoxia Exposure Is Impaired in NRF2-Deficient Mice
Authors: Reddy Narsa M. , Suryanarayana Vegiraju , Kalvakolanu Dhananjaya V. , Yamamoto Masayuki , Kensler Thomas W. , Hassoun Paul M. , Kleeberger Steven R. , Reddy Sekhar P.
Published: September 2009

Oxygen supplementation is used as therapy to support critically ill patients with severe respiratory impairment. Although hyperoxia has been shown to enhance the lung susceptibility to subsequent bacterial infection, the mechanisms underlying enhanced susceptibility remain enigmatic. We have reported that disruption of NF-E2-related factor 2 (Nrf2), a master transcription regulator of various stress response pathways, enhances susceptibility to hyperoxia-induced acute lung injury in mice, and have also demonstrated an association between a polymorphism in the NRF2 promoter and increased susceptibility to acute lung injury. In this study, we show that Nrf2-deficient (Nrf2−/−) but not wild-type (Nrf2+/+) mice exposed to sublethal hyperoxia succumbed to death during recovery after Pseudomonas aeruginosa infection. Nrf2-deficiency caused persistent bacterial pulmonary burden and enhanced levels of inflammatory cell infiltration as well as edema. Alveolar macrophages isolated from Nrf2−/− mice exposed to hyperoxia displayed persistent oxidative stress and inflammatory cytokine expression concomitant with diminished levels of antioxidant enzymes, such as Gclc, required for glutathione biosynthesis. In vitro exposure of Nrf2−/− macrophages to hyperoxia strongly diminished their antibacterial activity and enhanced inflammatory cytokine expression compared with Nrf2+/+ cells. However, glutathione supplementation during hyperoxic insult restored the ability of Nrf2−/− cells to mount antibacterial response and suppressed cytokine expression. Thus, loss of Nrf2 impairs lung innate immunity and promotes susceptibility to bacterial infection after hyperoxia exposure, ultimately leading to death of the host.
CXCR3 Directs Antigen-Specific Effector CD4+ T Cell Migration to the Lung During Parainfluenza Virus Infection
Authors: Kohlmeier Jacob E. , Cookenham Tres , Miller Shannon C. , Roberts Alan D. , Christensen Jan P. , Thomsen Allan R. , Woodland David L.
Published: September 2009

Effector T cells are a crucial component of the adaptive immune response to respiratory virus infections. Although it was previously reported that the chemokine receptors CCR5 and CXCR3 affect trafficking of respiratory virus-specific CD8+ T cells, it is unclear whether these receptors govern effector CD4+ T cell migration to the lungs. To assess the role of CCR5 and CXCR3 in vivo, we directly compared the migration of Ag-specific wild-type and chemokine receptor-deficient effector T cells in mixed bone marrow chimeric mice during a parainfluenza virus infection. CXCR3-deficient effector CD4+ T cells were 5- to 10-fold less efficient at migrating to the lung compared with wild-type cells, whereas CCR5-deficient effector T cells were not impaired in their migration to the lung. In contrast to its role in trafficking, CXCR3 had no impact on effector CD4+ T cell proliferation, phenotype, or function in any of the tissues examined. These findings demonstrate that CXCR3 controls virus-specific effector CD4+ T cell migration in vivo, and suggest that blocking CXCR3-mediated recruitment may limit T cell-induced immunopathology during respiratory virus infections.
Wireless Sensor Network Platforms
Authors: Bischoff Reinhard , Meyer Jonas , Feltrin Glauco
Published: September 2009

A wireless sensor network is a network made up of many tiny intercommunicating computers equipped with one or several sensors. Each tiny computer represents a node of the network. The nodes are self‐contained units typically consisting of a power supply with limited capacity, a radio transceiver, a microcontroller, and one or more sensors. This article gives an introduction to wireless sensor networks for structural health monitoring, shows the general architecture of sensor nodes, and overviews current hardware and software platforms. Furthermore, it shows the characteristics and limits of such monitoring systems and gives advice to choose a suitable platform to an application. Because nodes are powered by an autonomous source, energy‐related aspects, energy storage, and scavenging are presented as well.
Alkaline hydrolysis of cinnamaldehyde to benzaldehyde in the presence of β‐cyclodextrin
Authors: Chen Hongyan , Ji Hongbing
Published: September 2009

A facile, novel, and cost‐effective alkaline hydrolysis process of cinnamaldehyde to benzaldehyde under rather mild conditions has been investigated systematically in the presence of β‐cyclodextrin (β‐CD), with water as the only solvent. β‐CD could form inclusion complex with cinnamaldehyde in water, with molar ratio of 1:1, so as to promote the reaction selectivity. The complex has been investigated experimentally and with computational methods. 1H‐NMR, ROESY, UV–Vis, and FTIR have been utilized to analyze the inclusion complex. It shows that the equilibrium constant for inclusion (Ka) is 363 M−1, and the standard Gibbs function for the reaction, ΔγG (298 K), is −14.6 kJ mol−1. In addition, the structures of the proposed inclusion compounds were optimized with hybrid ONIOM theory. Benzaldehyde could be obtained at an yield of 42% under optimum conditions [50°C, 18 h, 2% NaOH (w/v), cinnamaldehyde:β‐CD (molar ratio) = 1:1]. To explain the experimental data, NMR, FTIR, and elemental analysis results were used to determine the main reaction by‐product 1‐naphthalenemethanol. A feasible reaction mechanism including the retro‐Aldol condensation of cinnamaldehyde and the Aldol condensation of acetaldehyde and cinnamaldehyde in basic aqueous β‐CD solution has been proposed. The calculated activation energy for the reaction was 45.27 kJ mol−1 by initial concentrations method. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Placental insulin‐like growth factor II (IGF‐II) and its relation to litter size in the common marmoset monkey (Callithrix jacchus)
Authors: Rutherford Julienne N. , Eklund Amy , Tardif Suzette
Published: September 2009

The primate placenta produces a wide variety of hormones throughout gestation that regulate placental function and fetal growth. One such hormone is insulin‐like growth factor‐II (IGF‐II), a peptide implicated in cell division, differentiation, and amino acid transport. IGF‐II concentrations were measured in 23 common marmoset (Callithrix jacchus) term placentas from twin and triplet litters in order to determine whether previously described differences in fetoplacental phenotype such as placental and litter mass and placental surface area were related to differences in endocrine function. IGF‐II was extracted from frozen tissue samples and measured using an enzyme‐linked immunosorbent assay kit designed for human tissue, which was validated for marmoset placenta. IGF‐II concentrations were not related to placental or litter mass, and twin and triplet placentas did not differ in total concentration. However, per individual fetus, triplets were associated with a significant 42% reduction in IGF‐II concentration (P=0.03), and IGF‐II concentration per gram of fetal mass was a third lower in triplet litters. The triplet placenta exhibits a global expansion of the surface area which was contrasted by a per unit area reduction in IGF‐II concentration (r=−0.75, P=0.01), a pattern that explains why twin and triplet placentas overall did not differ in concentration. Per fetus, triplet pregnancies are associated with relatively less maternal mass, placental mass and microscopic surface area suggesting that the intrauterine growth of triplets is supported by systems that increase the efficiency of nutrient transfer. The finding that individual triplet fetuses are also associated with significantly lower IGF‐II concentrations is consistent with the view that the marmoset fetoplacental unit exhibits a flexible pattern of placental allocation and metabolism. Plasticity in placental endocrine and metabolic function is likely to play an important role in the ability of the fetus to sense and accommodate the intrauterine environment and, by extension, the external ecology. Am. J. Primatol. 71:969–975, 2009. © 2009 Wiley‐Liss, Inc.
Robust H∞ control for uncertain discrete‐time systems with probabilistic state delays
Authors: Tian Engang , Yue Dong , Wang Zidong
Published: September 2009

In this paper, we propose a novel design problem of robust H∞ control for discrete‐time systems with probabilistic time delay, where both the variation range of the delay and the probability distribution of the delay taking values in an interval are available. Based on the information on the probability distribution of the delay taking values in an interval, a new modeling method is put forward, with which the probabilistic effects of the delay are reflected into a parameter matrix of certain transformed system. Based on such a new model, criteria for the H∞ control design are derived by using a combination of the convexity of the matrix equations, the Lyapunov functional method and the linear matrix inequality technique. It is shown via numerical examples that our developed method in the paper can lead to less conservative results than those obtained by existing methods and, furthermore, if the probability distribution of the delay occurrence is available, the allowable upper bound of the delay may be larger than those derived for the case when only the variation range of the delay can be known. Copyright © 2009 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Constrained PID tracking control for output PDFs of non‐gaussian stochastic system based on LMIs
Authors: Yi Yang , Shen Hong , Guo Lei
Published: September 2009

This paper presents a new PID tracking control strategy for general non‐Gaussian stochastic systems based on a square root B‐spline model for the output probability density functions (PDFs). Using the B‐spline expansion with modeling errors and the nonlinear weight model with exogenous disturbances, the PDF tracking is transformed to a constrained dynamical tracking control problem for weight vectors. Instead of the non‐convex design algorithms, the generalized PID controller structure and the improved convex linear matrix inequality (LMI) algorithms are proposed to fulfil the PDF tracking problem. Meanwhile, in order to enhance robustness, the robust peak‐to‐peak measure is applied to optimize the tracking performance. Copyright © 2009 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Adaptive output feedback control for a class of planar nonlinear systems
Authors: Shang Fang , Liu Yungang , Zhang Chenghui
Published: September 2009

This paper is concerned with the problem of global adaptive stabilization by output feedback for a class of planar nonlinear systems with uncertain control coefficient and unknown growth rate. The control coefficient is not supposed to have known upper bound, and this relaxes the corresponding requirement in the existing literature (see e.g. 1, 2. First, by the universal control method, an observer is constructed based on the dynamic high‐gain K‐filters. Then, the control design procedure is developed to obtain the stabilizing controller and dynamic compensator for the uncertainties in the control coefficient. It is shown that the global stability of the closed‐loop system can be guaranteed by the appropriate choice of the design parameters. A simulation example is also provided to illustrate the correctness of the theoretical results. © 2009 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society.
Mood and judgments based on sequential sampling
Authors: Fiedler Klaus , Renn Sven‐Yves , Kareev Yaakov
Published: September 2009

Different adaptive styles characterize cognition and behavior in different affective states. Whereas negative affect supports accommodation (i.e., stimulus‐driven bottom‐up processing), positive affect supports assimilation (i.e., self‐determined top‐down processing). Applying this well‐established rule to binary choices after self‐truncated information sampling, we predicted that positive mood should render choices less dependent on large samples than negative mood. Consequently, the potential primacy advantage underlying Wald's (1947) sequential testing (i.e., quick and correct decisions from the first few items in a sample) was exploited more efficiently when participants were in positive rather than negative mood. This efficient utilization of small samples in positive mood was obtained under the very conditions derived on a priori ground from a statistical model, namely, when a response criterion or threshold was high and when the true difference between choice options was relatively small. Copyright © 2009 John Wiley & Sons, Ltd.
High‐performance liquid chromatography separation of enantiomers of mandelic acid and its analogs on a chiral stationary phase
Authors: Aneja Ritu , Luthra Pratibha Mehta , Ahuja Satinder
Published: September 2009

The enantiomers of mandelic acid and its analogs have been chromatographically separated on a chiral stationary phase (CSP) derived from 4‐(3,5‐dinitrobenzamido) tetrahydrophenanthrene. The rationale of separations of these compounds is discussed with respect to the method development for determining enantiomeric purity and possibility of obtaining enantiomerically pure materials by high‐pressure liquid chromatography. The relationship of analyte structure to the extent of enantiomeric separation has been examined and separation factors (α) are presented for various groups of structurally related compounds. Chiral recognition models have been suggested to account for the observed separations. These models provide mechanistic insights into the chiral recognition process. Chirality 2010. © 2009 Wiley‐Liss, Inc.
Production of (R)‐1‐phenylethanols through bioreduction of acetophenones by a new fungus isolate Trichothecium roseum
Authors: Zilbeyaz Kani , Taskin Mesut , Kurbanoglu Esabi B. , Kurbanoglu Namudar I. , Kilic Hamdullah
Published: September 2009

A total of 120 fungal strains were isolated from soil samples and evaluated in the bioreduction of substituted acetophenones to the corresponding (R)‐alcohols. Among these strains, isolate Trichothecium roseum EBK‐18 was highly effective in the production of (R)‐alcohols with excellent enantioselectivity (ee > 99%). Gram scale preparation of (R)‐1‐phenylethanol is reported. Chirality 2010. © 2009 Wiley‐Liss, Inc.
Determination of the absolute configuration of the natural product klaivanolide via density functional calculations of vibrational circular dichroism (VCD)
Authors: Devlin Frank J. , Stephens Philip J. , Figadère Bruno
Published: September 2009

The absolute configuration (AC) of the antiprotozoal lactone, Klaivanolide, 1, from Uvaria klaineana, has been determined using Vibrational Circular Dichroism (VCD) spectroscopy. The experimental VCD spectrum of the (+) enantiomer of 1 was measured. To analyze the AC of (+)‐1, the conformationally‐averaged VCD spectrum of 7‐S‐1 was calculated using density functional theory (DFT) and the GAUSSIAN 03 program. The B3PW91/TZ2P conformationally‐averaged VCD spectrum of 7‐S‐1 proves that the AC of 1 is 7‐S‐(+). Chirality 21:E48–E53, 2009. © 2009 Wiley‐Liss, Inc.
Infectious Thoracic Aortitis: A Literature Review
Authors: Lopes R.J. , Almeida J. , Dias P.J. , Pinho P. , Maciel M.J.
Published: September 2009

Infectious thoracic aortitis (IA) remains a rare disease, especially after the appearance of antibiotics. However, if left untreated it is always lethal. It usually affects patients with atherosclerotic aortic disease and/or infective endocarditis. Mycotic aneurysm is the most common form of presentation, although a few reports of nonaneurysmal infectious thoracic aortitis have also been described. Various microorganisms have been associated with infectious thoracic aortitis, most commonly Staphylococcal, Enterococcus, Streptococcus, and Salmonella species. It is extremely important to establish an early diagnosis of IA, because this condition is potentially life‐threatening. However, diagnosis is frequently delayed since clinical manifestations are usually nonspecific. Antibiotherapy in combination with complete surgical excision of the infected aorta is the best choice of treatment. Copyright © 2009 Wiley Periodicals, Inc.
The Usage Patterns of Cardiac Bedside Markers Employing Point‐of‐Care Testing for Troponin in Non‐ST‐Segment Elevation Acute Coronary Syndrome: Results from CRUSADE
Authors: Takakuwa Kevin M. , Ou Fang‐Shu , Peterson Eric D. , Pollack Charles V. , Peacock W. Frank , Hoekstra James W. , Ohman E. Magnus , Gibler W. Brian , Blomkalns Andra L. , Roe Matthew T.
Published: September 2009

Background

Point‐of‐care (POC) testing may expedite the care of emergency department (ED) patients suspected of having acute coronary syndromes (ACS). We evaluated the use patterns of cardiac bedside markers or POC testing for troponin in patients with non‐ST‐segment elevation (NSTE) ACS.

Methods

NSTE ACS data were collected from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association (ACC/AHA) Guidelines (CRUSADE) registry. We compared hospital and patient characteristics, in‐hospital events, and process‐of‐care variables between hospitals to those that did not use POC testing in ≥ 50% of enrolled patients. We examined characteristics, in‐hospital events, and process‐of‐care differences between patients with negative vs positive troponin POC testing results.

Results

Of 568 hospitals, 74 (16,276 patients) had high POC usage compared with 197 hospitals (50 782 patients) with no troponin POC usage. From the high POC usage hospitals, 12 604 patients had recorded troponin POC test results. Hospitals with high POC usage had a shorter ED length of stay and were less likely to administer aspirin, β‐blockers, and heparin during the first 24 hours of care. Patients with positive troponin POC results were more often older, minority, female, Medicare‐insured, diabetic, and renally impaired. They had fewer electrocardiograms within 10 minutes but were more likely to get aspirin, β‐blockers, glycoprotein IIb/IIIa inhibitors, and heparin within 24 hours of arrival. They also had longer ED lengths of stay, received fewer in‐hospital and interventional procedures, and had more adverse clinical events.

Conclusion

Differences existed in how hospitals used POC testing and the care given based on those results. Positive POC results are associated with expedited and higher use of anti‐ischemic therapies. Copyright © 2009 Wiley Periodicals, Inc.
Fluorescence‐based quantitative scratch wound healing assay demonstrating the role of MAPKAPK‐2/3 in fibroblast migration
Authors: Menon Manoj B. , Ronkina Natalia , Schwermann Jessica , Kotlyarov Alexey , Gaestel Matthias
Published: September 2009

The scratch wound healing assay is a sensitive method to characterize cell proliferation and migration, but it is difficult to be quantitatively evaluated. Therefore, we developed an infrared fluorescence detection‐based real‐time assay for sensitive and accurate quantification of cell migration in vitro. The method offers sensitivity, simplicity, and the potential for integration into automated large‐scale screening studies. A live cell staining lipophilic tracer—1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethyl indotricarbocyanine iodide (DiR)—is used for accurate imaging of wound closure in a simple 96‐well scratch assay. Scratches are made on prestained confluent cell monolayers using a pipette tip and scanned at different time intervals using a fluorescent scanner. Images are analyzed using Image J software and the migration index is calculated. Effect of cell number, time after scratch and software settings are analyzed. The method is validated by showing concentration‐ and time‐dependent effects of cytochalasin‐D on fibroblast migration. Using this assay, we quantitatively evaluate the role of the MAPK‐activated protein kinases MK2 and MK3 in fibroblast migration. First, the migratory phenotype of MK2‐deficient MEFs is analyzed in a retroviral rescue model. In addition, migration of MK2/3‐double‐deficient cells is determined and the ability of MK3 to rescue cell migration in MK2/3‐double‐deficient fibroblasts is demonstrated. Cell Motil. Cytoskeleton 2009. © 2009 Wiley‐Liss, Inc.
Optical properties of non‐centrosymmetric mixed crystals K2(La1‐xCex)(NO3)5 · 2 H2O (x = 0.0 – 1.0)
Authors: Bohatý L. , Becker P.
Published: September 2009

Large single crystals of optical quality of the non‐centrosymmetric orthorhombic potassium rare earth nitrate mixed crystals K2(La1–x Cex)(NO3)5 · 2 H2O were grown at 38 °C from diluted HNO3. For crystals with x = 0.0, 0.19, 0.38 and 0.66 refractive indices and their dispersion were determined with an error less than 1 · 10–4 in the wavelength range 0.404 – 1.083 μm by the prism method. Phase matching conditions for collinear SHG frequency conversion were analysed in detail, including calculation of the effective nonlinear optical susceptibility. By an appropriate choice of the fraction x of cerium the mixed crystals K2(La1–x Cex)(NO3)5 · 2 H2O allow an adjustment of non‐critical type I phase matching conditions to a desired wavelength of the fundamental wave within the range 1.055(4) – 1.107(6) μm. Non‐critical type II phase matching can be tuned in the wavelength range 0.949(2) – 0.931(2) μm. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Microscopic lateral overgrowth by physical vapour transport of GaN on self‐organized diamond‐like carbon masks
Authors: Gogova D. , Albrecht M. , Remmele T. , Irmscher K. , Siche D. , Rost H.‐J. , Schmidbauer M. , Fornari R. , Yakimova R.
Published: September 2009

Techniques to reduce dislocation densities in GaN grown on foreign substrates are an interesting alternative to bulk growth as long as efficient bulk crystals growth techniques are not available. In this paper a new approach for epitaxial lateral overgrowth (ELO) of GaN through an in‐situ grown self‐organized amorphous (diamond‐like) carbon mask is demonstrated. The ELO was done for the first time by physical vapour transport of Ga, using NH3 as a nitrogen source. The overgrowth results in a decrease of the threading dislocation density by at least one order of magnitude compared to that of the MOCVD GaN/sapphire templates. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Identification of a NCR+/NKG2D+/LFA‐1low/CD94− immature human NK cell subset
Authors: Zamai Loris , Galeotti Laura , Zotto Genny Del , Canonico Barbara , Mirandola Prisco , Papa Stefano
Published: September 2009

CD56bright natural killer (NK) cells, generated in vitro from CD34+ hematopoietic progenitor cells, were characterized after a 30‐day culture with flt3 ligand plus IL‐15. Virtually, all CD56bright cells expressed CD117, CD25, natural cytotoxicity receptors (NCRs), NKG2D, CD161, and CD244, while only a subset expressed CD18‐CD11a (LFA‐1), and CD94 molecule, defining an immature CD56bright/NCRs+/NKG2D+/LFA‐1−/CD94− subset. Another small subset of cells expressing CD94 but not LFA‐1 integrin was also identified, suggesting that during NK differentiation LFA‐1 might be upregulated later than CD94. To verify this hypothesis in vivo, we evaluated the NK cell expression of LFA‐1 in both peripheral and umbilical cord blood samples. Interestingly, in these blood fluids, we have identified a lineage negative CD34−/LFA‐1low/NKp46dim/NKG2Ddim/CD94− subset that resembled an immature stage of NK cells present in lymph nodes. Altogether, the results indicate that CD18‐CD11a integrin, as well as CD11b in mice, may be a useful marker to identify immature stages of NK cell differentiation. © 2009 International Society for Advancement of Cytometry
Practical multiple‐antenna solutions for enhancing adaptive OFDM performance in mm‐wave WPANs
Authors: Holland I. D. , Hall L. T. , Cowley W. G.
Published: September 2009

The design of short‐range high‐speed wireless networks for the 60 GHz band requires consideration of factors from a wide range of disciplines. Key system choices that make significant differences to the final cost and performance include the type of antennas, multiple access strategy and channel coding. In this paper we assume a coded orthogonal frequency division multiplexing (OFDM) system providing high‐speed communications between low‐cost terminals over indoor 60 GHz channels that are frequently non‐line‐of‐sight. Under constraints of low transmit power and high path attenuation, we consider two practical options for using multiple low‐cost ‘bond‐wire’ antennas, compared with ideal monopole antennas at each terminal. For specified multiple access and channel coding schemes, we show that a sectorized strategy based on simple 2 element phased arrays can provide substantial benefits in system performance and flexibility. Copyright © 2009 John Wiley & Sons, Ltd.
Handling high mobility in next‐generation wirelessad hocnetworks
Authors: Ho Ai Hua , Ho Yao Hua , Hua Kien A.
Published: September 2009

Next‐generationad hocnetworks need to be able to handle high mobility in order to support a wide range of emerging applications such as vehicular networks. Maintaining communication links of an established communication path that extends between source and destination nodes is a significant challenge in mobilead hocnetworks due to the movement of the mobile nodes. In particular, such communication links are often broken under a high mobility environment. Although a new communication route can be established when a break in the communication path occurs, repeatedly reestablishing new routes incurs delay and substantial overhead. To address this limitation, we introduce theVirtual Routerabstraction in this paper. A virtual router is a dynamically created logical router that is associated with a particular geographical area. Its routing functionality is provided by the physical nodes (i.e. mobile devices) currently within the geographical region served by the virtual router. These physical nodes take turns in forwarding data packets for the virtual router. In this environment, data packets are transmitted from a source node to a destination node over a series of virtual routers. Since virtual routers do not move, this scheme is much less susceptible to node mobility. We give simulation results to demonstrate the effectiveness of this technique in handling high mobility. They show that the Virtual Router approach can achieve several times better performance than the traditional approach based on physical routers (i.e. relay nodes). Copyright © 2009 John Wiley & Sons, Ltd.