bluuebunny/crossref_metadata_2025 huggingface dataset:
CXCR2 Is Required for Neutrophilic Airway Inflammation and Hyperresponsiveness in a Mouse Model of Human Rhinovirus Infection
Authors: Nagarkar Deepti R. , Wang Qiong , Shim Jee , Zhao Ying , Tsai Wan C. , Lukacs Nicholas W. , Sajjan Uma , Hershenson Marc B.
Published: October 2009

Human rhinovirus (RV) infection is responsible for the majority of virus-induced asthma exacerbations. Using a mouse model of human RV infection, we sought to determine the requirement of CXCR2, the receptor for ELR-positive CXC chemokines, for RV-induced airway neutrophilia and hyperresponsiveness. Wild-type and CXCR2−/− mice were inoculated intranasally with RV1B or sham HeLa cell supernatant. Following RV1B infection, CXCR2−/− mice showed reduced airway and lung neutrophils and cholinergic responsiveness compared with wild-type mice. Similar results were obtained in mice treated with neutralizing Ab to Ly6G, a neutrophil-depleting Ab. Lungs from RV-infected, CXCR2−/− mice showed significantly reduced production of TNF-α, MIP-2/CXCL2, and KC/CXCL1 and lower expression of MUC5B compared with RV-treated wild-type mice. The requirement of TNF-α for RV1B-induced airway responses was tested using TNFR1−/− mice. TNFR1−/− animals displayed reduced airway responsiveness to RV1B, even when exogenous MIP-2 was added to the airways. We conclude that CXCR2 is required for RV-induced neutrophilic airway inflammation and that neutrophil TNF-α release is required for airway hyperresponsiveness.
AS04, an Aluminum Salt- and TLR4 Agonist-Based Adjuvant System, Induces a Transient Localized Innate Immune Response Leading to Enhanced Adaptive Immunity
Authors: Didierlaurent Arnaud M. , Morel Sandra , Lockman Laurence , Giannini Sandra L. , Bisteau Michel , Carlsen Harald , Kielland Anders , Vosters Olivier , Vanderheyde Nathalie , Schiavetti Francesca , Larocque Daniel , Van Mechelen Marcelle , Garçon Nathalie
Published: October 2009

Adjuvant System 04 (AS04) combines the TLR4 agonist MPL (3-O-desacyl-4′-monophosphoryl lipid A) and aluminum salt. It is a new generation TLR-based adjuvant licensed for use in human vaccines. One of these vaccines, the human papillomavirus (HPV) vaccine Cervarix, is used in this study to elucidate the mechanism of action of AS04 in human cells and in mice. The adjuvant activity of AS04 was found to be strictly dependent on AS04 and the HPV Ags being injected at the same i.m. site within 24 h of each other. During this period, AS04 transiently induced local NF-κB activity and cytokine production. This led to an increased number of activated Ag-loaded dendritic cells and monocytes in the lymph node draining the injection site, which further increased the activation of Ag-specific T cells. AS04 was also found to directly stimulate those APCs in vitro but not directly stimulate CD4+ T or B lymphocytes. These AS04-induced innate responses were primarily due to MPL. Aluminum salt appeared not to synergize with or inhibit MPL, but rather it prolonged the cytokine responses to MPL at the injection site. Altogether these results support a model in which the addition of MPL to aluminum salt enhances the vaccine response by rapidly triggering a local cytokine response leading to an optimal activation of APCs. The transient and confined nature of these responses provides further supporting evidence for the favorable safety profile of AS04 adjuvanted vaccines.
Differential Cytokine Production and Bystander Activation of Autoreactive B Cells in Response to CpG-A and CpG-B Oligonucleotides
Authors: Avalos Ana M. , Latz Eicke , Mousseau Betty , Christensen Sean R. , Shlomchik Mark J. , Lund Frances , Marshak-Rothstein Ann
Published: October 2009

Synthetic oligonucleotides containing CpG motifs have been shown to induce proliferation, differentiation, and cytokine production in B cells, macrophages, and dendritic cells through a TLR9-dependent mechanism. A class (CpG-A) and B class (CpG-B) oligonucleotides display distinct physical properties. CpG-A, but not CpG-B, can multimerize to form exceedingly large lattices. CpG-A cannot effectively activate B cells but does induce plasmacytoid dendritic cells to produce high levels of IFNα, while CpG-B is a potent B cell mitogen. In this study, we report that CpG-A is internalized by B cells, and CpG-A and CpG-B accumulate in distinct intracellular compartments. When present in the form of an immune complex (CpG-A IC), CpG-A is taken up more efficiently by AM14 IgG2a-specific B cells, and elicits a robust TLR9-dependent B cell proliferative response. B cells proliferating comparably and in a TLR9-dependent fashion in response to CpG-A IC and CpG-B exhibited distinct cytokine profiles. CpG-A IC induced enhanced production of RANTES and markedly reduced levels of IL-6 when compared with CpG-B. We also found that engagement of the AM14 BCR by a protein IC, which cannot by itself induce proliferation, promoted TLR9-dependent but BCR-independent proliferation by bystander CpG-A or fragments of mammalian dsDNA. These data identify direct and indirect mechanisms by which BCR engagement facilitates access of exogenous ligands to TLR9-associated compartments and subsequent B cell activation.
Aluminum Alloys and Engineered Materials
Authors: Sansonetti S.J.
Published: October 2009

Contemporary Advancements and Future Potential
Memory, Electronic—Chronology to 1990
Authors: Brunner R.
Published: October 2009

Historical Perspective

Read‐Only Memories (
ROM
s)

The Groundwork for Creating the Electronic Memories of the 1990s Transferring Data between Functional Modules
Optical Fiber Systems
Authors:   Lucent Technologies, Optical Fiber Solutions
Published: October 2009

Fiber‐Optic Systems in Perspective

Types of Optical Fibers

Characteristics Affecting Optical Fiber Performance

Glass Processing

Improvements in Lasers

Light‐Emitting Diode for Telecommunications

Erbium‐Doped Fibers for Amplification

Optical Fibers in Aircraft

Fiber Optics in Biomedicine

Fiber Optic Communications in Botany

Fiber Optics in the Private Network

Fiber Optics in Industrial Instrumentation and Networks

Optical Fiber Terminology
Organic Light‐Emitting Diodes (
OLED
s)
Authors:   Stanford Resources, Inc.
Published: October 2009

Monochromatic
OLED
Devices

Organic Light‐Emitting Molecules
Precipitation and Hydrometeors
Authors: Kraght Peter E.
Published: October 2009

Condensation in the Atmosphere

Sublimation in the Atmosphere

Saturation, Supersaturation, and Supercooling

Cloud Process

Specific Types of Hydrometeors and Precipitation

Measurement of Hydrometeors and Precipitation Phenomena
Scatterometry
Authors:   NASA'Jet Propulsion Laboratory
Published: October 2009

The Science of Scatterometry

Applications: Observing Oceans from Space

Missions
Sexually Transmitted Diseases
Authors:   Centers for Disease Control and Prevention (CDC)
Published: October 2009

Chlamydia

Gonorrhea

Syphilis

Symptoms

Diagnosis and Treatment

Genital Warts (Human PapillomavirusHPV)

Genital Herpes (Herpes Simplex VirusHSV)

HepatitisB(HBV)

Trichomoniasis

Bacterial Vaginosis (BV)

The Role ofSTDDetection and Treatment inHIVPrevention

What Are the Implications forHIVPrevention Programs?

STDsand Pregnancy

Pelvic Inflammatory Disease (PID)
Supernova 1987A and 1993J
Authors: Pesch Peter
Published: October 2009

Supernova 1987A

Supernova 1993J
The kinetics of the reduction of iron oxide by carbon monoxide mixed with carbon dioxide
Authors: Bohn C. D. , Cleeton J. P. , Müller C. R. , Davidson J. F. , Hayhurst A. N. , Scott S. A. , Dennis J. S.
Published: October 2009

Results are reported for the repeated reduction of iron oxide particles, 300–425 μm diameter, by a mixture of CO, CO2, and N2 in a fluidized bed of 20 mm internal diameter. The conclusions were as follows: (1) Reduction of either Fe2O3 to Fe3O4 or of Fe3O4 to Fe0.947O is first‐order in CO. (2) With the particle sizes used, the rates of the reduction reactions are controlled by intrinsic chemical kinetics. Activation energies and pre‐exponential factors are reported. (3) The first cycle gave anomalous results, but (a) the rate of reduction of Fe2O3 to Fe3O4 remained constant over cycles 2–10; (b) the rate of reduction of Fe3O4 to Fe0.947O declined by 60–85% over cycles 2–10. (4) The rates of reduction declined with solids conversion down to zero at 80% conversion. The rates were incorporated into a conventional model of a fixed bed, which was used to predict, satisfactorily, the reduction behavior of iron oxide. © 2009 American Institute of Chemical Engineers AIChE J, 2010
Katalyse mit Palladium in hoher Oxidationsstufe: neue Reaktivität für die organische Synthese
Authors: Muñiz Kilian
Published: October 2009

Die vergangenen Jahre waren Zeuge der schnellen Entwicklung eines neuen Gebiets der Palladium‐Katalyse in der organischen Synthese. Entsprechende Reaktionen verlaufen außerhalb der normalerweise beobachteten Pd0/PdII‐Katalysezyklen und werden durch die Gegenwart starker Oxidationsmittel ermöglicht, die an einem gegebenen Punkt des Katalysezyklus weitere Palladium(II)‐Reaktionen durch selektive Oxidation des Metalls verhindern. Die dabei entstehenden Palladium‐Komplexe in höherem Oxidationszustand sind für die Entwicklung einer Reihe von neuen Umwandlungen genutzt worden, die nicht über herkömmliche Palladium‐Katalysen realisiert werden können. Eine derartige Katalyse mit Palladium in höherem Oxidationszustand ist von erheblichem Synthesepotenzial.
Thermomechanical processing environment and morphology development of a thermotropic polymer liquid crystal
Authors: Viana Júlio C. , Simões Ricardo , Mano João F. , Oliveira Maria. J. , Denchev Zlatan Z. , Brostow Witold , Cunha António M.
Published: October 2009

We have studied a longitudinal polymer liquid crystal consisting of poly(ethylene terephthalate) (PET) and p‐hydroxybenzoic acid, namely PET/0.6PHB, where 0.6 is the mole fraction of the second component. The material was injection molded with systematic variations of the melt and mold temperatures and injection flow rate using design of experiments based on a Taguchi orthogonal array. Thermomechanical environment defined by local melt temperatures and shear rates and stresses imposed during processing was estimated by computer simulations of the mold‐filling phase. The morphology of the moldings was characterized by optical and scanning electronic microscopy, wide‐ and small‐angle X‐ray scattering, and differential scanning calorimetry. An analysis of variance approach identified the significant processing variables and their contributions to variations of morphological parameters. The processing environment affects strongly the melt viscosity, and there is a strong thermo‐mechanical coupling. The result is a complex multilaminated and hierarchical microstructure, whose morphological features are very sensitive to the processing conditions. Relationships between local thermomechanical variables (rather than global ones) and the morphological parameters are established. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Thermal aging of a blend of high‐performance fibers
Authors: Arrieta Carlos , David Eric , Dolez Patricia , Vu‐Khanh Toan
Published: October 2009

The focus of this work is the study of the thermal aging of high‐performance fibers used in the making of fire protective garments. Accelerated thermal aging tests were carried out on fabric samples made up of a blend of Kevlar® (poly p‐phenylene terephthalamide) and PBI (poly benzimidazole) staple fibers, as well as on yarns pulled from this fabric, by means of exposure to elevated temperatures, comprised between 190°C and 320°C. All samples underwent loss of breaking force retention. The material thermal life, defined as the time required for the fibers to attain a 50% reduction of the original breaking force, ranged between a dozen of days at the lowest exposure temperature, to less than an hour at the highest. Breaking force data were fitted using the Arrhenius model following two different approaches, namely the extrapolated thermal life value and the shift factors yielded by the time‐temperature superposition (TTS). The Arrhenius model seemed to describe appropriately the overall aging process, as inferred from the excellent fit obtained when using both approaches, although activation energies provided from both approaches are different. To follow the chemical evolution of the material with thermal aging, Fourier‐transform infrared (FTIR) analyses were conducted. The qualitative analysis of the FTIR spectra showed little evidence of chemical changes between the aged and the nonaged samples, indicating either that the aging process carries on without significant modification of the chemical structure of the fibers, or that FTIR is not an appropriate method to spot such a modification. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
The substituent effects on the structure and surface morphology of polyaniline
Authors: Sahin Mutlu , Özcan Levent , Özcan Ali , Usta Betül , Sahin Yücel , Pekmez Kadir
Published: October 2009

In this work, poly(2‐fluoroaniline), poly(2‐chloroaniline), poly(2‐methylaniline), and poly(N‐ethylaniline) were prepared by a self‐assembly method using an oxidizing system consisting of a dopant anion, p‐toluene sulfonate with ammonium peroxydisulfate. The effects of substituents on the surface morphology, conductivity, molecular weight, spectral and thermal properties of the polymers were studied. SEM results revealed that the surface morphology of the resulting polymers changed from nanofiber to spherical structure by changing the substituent on the aniline monomers. The structure and properties of these conducting films were characterized by FTIR, UV‐vis, elemental analysis, TGA, conductivity, and cyclic voltammetry. The polymer films show electroactivity in monomer free solution. Molecular weight of the polymers was determined by gel permeation chromatography. The dry electrical conductivity values of the substituted‐polyanilines were found to be lower than that of PANI. The results revealed that the molecular structures of the polymers were similar to those of the emeraldine form of polyaniline. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Polyvinyl alcohol fuller's earth clay nanocomposite films
Authors: Pandey Pratibha , Bhattacharyya Arup Ranjan , Gutch Pranav Kumar , Chauhan Ram Singh , Pant Satish Chandra
Published: October 2009

Nano fuller's earth was prepared by milling and subsequent sonication of clay. The polyvinyl alcohol (PVA) and PVA ‐Nano clay composite films were prepared by solution casting method. The films were characterized for their structural, mechanical, and thermal properties using electron microscopes (SEM, TEM), Tensile Tester, dynamic mechanical analyzer (DMA), thermo gravimetric analyzer (TGA), and Raman spectroscopy. The nanocomposite films showed improvement in mechanical properties, viscoelastic behavior as well as resistance towards thermal degradation. Uniform distribution of clay due to intimate interaction between clay and polymer appears to be the cause for improved properties. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Influence of branching on the thermal and crystallization behavior of bimodal polyethylenes synthesized with binary late‐transition‐metal catalyst combinations
Authors: Long Ying‐Yun , Liu San‐Rong , Cui Lei , Li Yue‐Sheng
Published: October 2009

Two reactor blends of linear and branched polyethylene resins with bimodal molecular weight distributions were synthesized in a one‐reactor polymerization process through the combination of 2,6‐bis[1‐(2,6‐dimethyphenylimino)pyridyl]cobalt dichloride (1) and 2,3‐bis(2,6‐diisopropylphenyl)butanediimine nickel dibromide (2) or 1,2‐bis(2,6‐diisopropylphenyl)cyclohexene diimine nickel dibromide (3) in the presence of modified methylaluminoxane. The linear correlation between the catalyst activity and concentration of the nickel compounds suggested that the catalysts performed independently of one another. The molecular weights, molecular weight distributions, and crystalline and phase structures of the blends were investigated with a combination of high‐temperature gel permeation chromatography, differential scanning calorimetry, wide‐angle X‐ray diffraction, and small‐angle X‐ray scattering techniques. The branching degree of the polyethylene produced with 3 was much higher than the branching degree of the sample produced with 2, although their molecular weights were relatively close. In addition, the crystallization rate, melting temperature, degree of crystallinity, and crystallization temperature of more highly branched blends produced with 1/3 were lower. The long periods and thickness of the crystalline region were greatly influenced by the addition of highly branched polyethylene. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010
Relationship Between Anticancer Activity and Stereochemistry of Saldach Ligands and their Iron(III) Complexes
Authors: Hille Annegret , Gust Ronald
Published: October 2009

(R,R)‐, (S,S)‐ and (R,S)‐N,N′‐bis(salicylidene)‐1,2‐diaminocyclohexane (saldach) and their iron(III) complexes were screened for anticancer activity against MCF‐7 and MDA‐MB 231 breast cancer as well as HT‐29 colon carcinoma cells. Antiproliferative effects depended on the presence of the central atom iron but were independent on the configuration at the saldach ligand. While the free ligands were inactive, the iron(III) derivatives displayed anticancer activity within a concentration range of 1 to 5 μM irrespective of the used cell line. At 5 μM they were even more active than cis‐platin. A mode of action comparable to cis‐platin can be excluded because it is very likely that the DNA is not the primary target of [FeIII (saldach)] complexes.
On a robust synchronization problem via internal model approach
Authors: Sun Weijie , Huang Jie
Published: October 2009

This paper formulates the synchronization of the Duffing system and the Van der Pol oscillator as a robust output regulation problem and presents the solution to this problem based on the internal model design. The controller thus obtained is able to achieve the synchronization of the outputs of these two systems in the presence of the parameter uncertainty of the Duffing system. Copyright © 2009 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
A diagnosis of warm‐core and cold‐core extratropical cyclone development using the Zwack–Okossi equation
Authors: Azad Roohollah , Sorteberg Asgeir
Published: October 2009

In this study, the development of a warm‐core and cold‐core extratropical cyclone over North Atlantic is examined. The geostrophic relative vorticity tendency used to diagnose the development is calculated utilizing the so‐called extended form of the Zwack–Okossi development equation. In both cases, the cyclonic vorticity advection acted to develop the system, but warm‐air advection (diabatic heating) made the largest contribution to explosive development in the cold‐core (warm‐core) case. Further, a vertical cross section of the temperature advection in the warm‐core case reveals that the largest values of this contributor are located far and ahead of the cyclone center. Copyright © 2009 Royal Meteorological Society
Signal transduction of the melatonin receptor MT1 is disrupted in breast cancer cells by electromagnetic fields
Authors: Girgert Rainer , Hanf Volker , Emons Günter , Gründker Carsten
Published: October 2009

The growth of estrogen‐receptor positive breast cancer cells is inhibited by the pineal gland hormone, melatonin. Concern has been raised that power‐line frequency and microwave electromagnetic fields (EMFs) could reduce the efficiency of melatonin on breast cancer cells. In this study we investigated the impact of EMFs on the signal transduction of the high‐affinity receptor MT1 in parental MCF‐7 cells and MCF‐7 cells transfected with the MT1 gene. The binding of the cAMP‐responsive element binding (CREB) protein to a promoter sequence of BRCA‐1 after stimulation with melatonin was analyzed by a gel‐shift assay and the expression of four estrogen‐responsive genes was measured in sham‐exposed breast cancer cells and cells exposed to a sinusoidal 50 Hz EMF of 1.2 µT for 48 h. In sham‐exposed cells, binding of CREB to the promoter of BRCA‐1 was increased by estradiol and subsequently diminished by treatment with melatonin. In cells exposed to 1.2 µT, 50 Hz EMF, binding of CREB was almost completely omitted. Expression of BRCA‐1, p53, p21WAF, and c‐myc was increased by estradiol stimulation and subsequently decreased by melatonin treatment in both cell lines, except for p53 expression in the transfected cell line, thereby proving the antiestrogenic effect of melatonin at molecular level. In contrast, in breast cancer cells transfected with MT1 exposed to 1.2 µT of the 50 Hz EMF, the expression of p53 and c‐myc increased significantly after melatonin treatment but for p21WAF the increase was not significant. These results convincingly prove the negative effect of EMF on the antiestrogenic effect of melatonin in breast cancer cells. Bioelectromagnetics 31:237–245, 2010. © 2009 Wiley‐Liss, Inc.
Protein disulfide isomerase does not control recombinant IgG4 productivity in mammalian cell lines
Authors: Hayes N.V.L. , Smales C.M. , Klappa P.
Published: October 2009

Post‐translational limitations in the endoplasmic reticulum during recombinant monoclonal antibody production are an important factor in lowering the capacity for synthesis and secretion of correctly folded proteins. Mammalian protein disulfide isomerase (PDI) has previously been shown to have a role in the formation of disulfide bonds in immunoglobulins. Several attempts have been made to improve the rate of recombinant protein production by overexpressing PDI but the results from these studies have been inconclusive. Here we examine the effect of (a) transiently silencing PDI mRNA and (b) increasing the intracellular levels of members of the PDI family (PDI, ERp72, and PDIp) on the mRNA levels, assembly and secretion of an IgG4 isotype. Although transiently silencing PDI in NS0/2N2 cells suggests that PDI is involved in disulfide bond formation of this subclass of antibody, our results show that PDI does not control the overall IgG4 productivity. Furthermore, overexpression of members of the PDI family in a Chinese hamster ovary (CHO) cell line does not improve productivity and hence we conclude that the catalysis of disulfide bond formation is not rate limiting for IgG4 production. Biotechnol. Bioeng. 2010. 105: 770–779. © 2009 Wiley Periodicals, Inc.
Model‐based high cell density cultivation of Rhodospirillum rubrum under respiratory dark conditions
Authors: Zeiger Lisa , Grammel Hartmut
Published: October 2009

The potential of facultative photosynthetic bacteria as producers of photosynthetic pigments, vitamins, coenzymes and other valuable products has been recognized for decades. However, mass cultivation under photosynthetic conditions is generally inefficient due to the inevitable limitation of light supply when cell densities become very high. The previous development of a new cultivation process for maximal expression of photosynthetic genes under semi‐aerobic dark conditions in common bioreactors offers a new perspective for utilizing the facultative photosynthetic bacterium Rhodospirillum rubrum for large‐scale applications. Based on this cultivation system, the present study aimed in determining the maximal achievable cell density of R. rubrum in a bioreactor, thereby providing a major milestone on the way to industrial bioprocesses. As a starting point, we focus on aerobic growth due to higher growth rates and more facile process control under this condition, with the option to extend the process by an anaerobic production phase. Process design and optimization were supported by an unstructured computational process model, based on mixed‐substrate kinetics. Key parameters for growth and process control were determined in shake‐flask experiments or estimated by simulation studies. For fed‐batch cultivation, a computer‐controlled exponential feed algorithm in combination with a pH‐stat element was implemented. As a result, a maximal cell density of 59 g cell dry weight (CDW) L−1 was obtained, representing so far not attainable cell densities for photosynthetic bacteria. The applied exponential fed‐batch methodology therefore enters a range which is commonly employed for industrial applications with microbial cells. The biochemical analysis of high cell density cultures revealed metabolic imbalances, such as the accumulation and excretion of tetrapyrrole intermediates of the bacteriochlorophyll biosynthetic pathway. Biotechnol. Bioeng. 2010. 105: 729–739. © 2009 Wiley Periodicals, Inc.
Bioreactor expansion of human neural precursor cells in serum‐free media retains neurogenic potential
Authors: Baghbaderani Behnam A. , Mukhida Karim , Sen Arindom , Kallos Michael S. , Hong Murray , Mendez Ivar , Behie Leo A.
Published: October 2009

Human neural precursor cells (hNPCs), harvested from somatic tissue and grown in vitro, may serve as a source of cells for cell replacement strategies aimed at treating neurodegenerative disorders such as Parkinson's disease (PD), Huntington's disease (HD), and intractable spinal cord pain. A crucial element in a robust clinical production method for hNPCs is a serum‐free growth medium that can support the rapid expansion of cells while retaining their multipotency. Here, we report the development of a cell growth medium (PPRF‐h2) for the expansion of hNPCs, achieving an overall cell‐fold expansion of 1013 over a period of 140 days in stationary culture which is significantly greater than other literature results. More importantly, hNPC expansion could be scaled‐up from stationary culture to suspension bioreactors using this medium. Serial subculturing of the cells in suspension bioreactors resulted in an overall cell‐fold expansion of 7.8 × 1013 after 140 days. These expanded cells maintained their multipotency including the capacity to generate large numbers of neurons (about 60%). In view of our previous studies regarding successful transplantation of the bioreactor‐expanded hNPCs in animal models of neurological disorders, these results have demonstrated that PPRF‐h2 (containing dehydroepiandrosterone, basic fibroblast growth factor and human leukemia inhibitory factor) can successfully facilitate the production of large quantities of hNPCs with potential to be used in the treatment of neurodegenerative disorders. Biotechnol. Bioeng. 2010. 105: 823–833. © 2009 Wiley Periodicals, Inc.
Dynamic flux responses in riboflavin overproducing Bacillus subtilis to increasing glucose limitation in fed‐batch culture
Authors: Rühl Martin , Zamboni Nicola , Sauer Uwe
Published: October 2009

How do intracellular fluxes respond to dynamically increasing glucose limitation when the physiology changes from strong overflow metabolism near to exclusively maintenance metabolism? Here we investigate this question in a typical industrial, glucose‐limited fed‐batch cultivation with a riboflavin overproducing Bacillus subtilis strain. To resolve dynamic flux changes, a novel approach to 13C flux analysis was developed that is based on recording 13C labeling patterns in free intracellular amino acids. Fluxes are then estimated with stationary flux ratio and iterative isotopomer balancing methods, for which a decomposition of the process into quasi‐steady states and estimation of isotopic steady state 13C labeling patterns was necessary. By this approach, we achieve a temporal resolution of 30–60 min that allows us to resolve the slow metabolic transients that typically occur in such cultivations. In the late process phase we found, most prominently, almost exclusive respiratory metabolism, significantly increased pentose phosphate pathway contribution and a strongly decreased futile cycle through the PEP carboxykinase. As a consequence, higher catabolic NADPH formation occurred than was necessary to satisfy the anabolic demands, suggesting a transhydrogenase‐like mechanism to close the balance of reducing equivalents. Biotechnol. Bioeng. 2010. 105: 795–804. © 2009 Wiley Periodicals, Inc.
Drug release and its relationship with kinetic and thermodynamic parameters of drug sorption onto starch acetate fibers
Authors: Xu Weijie , Yang Yiqi
Published: October 2009

Drug release and its relationship with kinetic and thermodynamic parameters of drug sorption onto starch acetate (SA) fibers have been studied using Diclofenac, 5‐Fluorouracil (5‐Fu), and Metformin as model drugs. The sorption method is more flexible and can avoid limitations or problems which occur with molten or dissolution methods. To understand drug release of sorption loading, kinetic and apparent thermodynamic parameters, such as diffusion coefficient, activation energy for diffusion, affinity, and sorption enthalpy and entropy, have been investigated. The quantitative relationship between drug release and drug‐loading concentration, affinity, and activation energy for diffusion has been established to predict the initial burst and subsequent release of the drugs. Up to 12% of Diclofenac, based on the weight of SA, can be loaded onto fibers using the sorption method. Drugs with higher activation energy for diffusion, lower diffusion coefficients, and higher affinity for SA fiber, such as Diclofenac, are more suitable for sorption loading. It has also been found that elevated temperatures will achieve higher loading capacity and a more constant release rate. Biotechnol. Bioeng. 2010. 105: 814–822. © 2009 Wiley Periodicals, Inc.
Comprehending Canadian police cautions: are the rights to silence and legal counsel understandable?
Authors: Eastwood Joseph , Snook Brent
Published: October 2009

Comprehension of a Canadian police right to silence caution and a right to legal counsel caution was examined. Each caution was first presented verbally in its entirety, followed by its sentence‐by‐sentence presentation in written format. Participants (N = 56) were asked to indicate, after each presentation, their understanding of the caution. When delivered in verbal format, 4 and 7% of participants fully understood the right to silence and legal counsel cautions, respectively. However, 48 and 32% of participants fully understood the right to silence and legal counsel cautions, respectively, when delivered in written format. Comprehension of the cautions was not influenced by gender, experience with the caution, or whether the caution was interpreted by a police recruit or regular student. The implications of the results for statement admissibility and protection of suspects' rights are discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Dynamic culture of droplet‐confined cell arrays
Authors: Cimetta Elisa , Cagnin Stefano , Volpatti Annamaria , Lanfranchi Gerolamo , Elvassore Nicola
Published: October 2009

Responding to the need of creating an accurate and controlled microenvironment surrounding the cell while meeting the requirements for biological processes or pharmacological screening tests, we aimed at designing and developing a microscaled culture system suitable for analyzing the synergic effects of extracellular matrix proteins and soluble environments on cell phenotype in a high‐throughput fashion. We produced cell arrays deposing micrometer‐scale protein islands on hydrogels using a robotic DNA microarrayer, constrained the culture media in a droplet‐like volume and developed a suitable perfusion system. The droplet‐confined cell arrays were used either with conventional culture methods (batch operating system) or with automated stable and constant perfusion (steady‐state operating system). Mathematical modeling assisted the experimental design and assessed efficient mass transport and proper fluidodynamic regimes. Cells cultured on arrayed islands (500 μm diameter) maintained the correct phenotype both after static and perfused conditions, confirmed by immunostaining and gene expression analyses through total RNA extraction. The mathematical model, validated using a particle tracking experiment, predicted the constant value of velocities over the cell arrays (less than 10% variation) ensuring the same mass transport regime. BrdU analysis on an average of 96 cell spots for each experimental condition showed uniform expression inside each cell island and low variability in the data (average of 13%). Perfused arrays showed longer doubling times when compared with static cultures. In addition, perfused cultures showed a reduced variability in the collected data, allowing to detect statistically significant differences in cell behavior depending on the spotted ECM protein. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010
A Conserved Lysine in β‐Lactam Synthetase Assists Ring Cyclization: Implications for Clavam and Carbapenem Biosynthesis
Authors: Raber Mary L. , Castillo Alvaro , Greer Alexander , Townsend Craig A.
Published: October 2009

β‐Lactam synthetase (β‐LS) is the paradigm of a growing class of enzymes that form the critical β‐lactam ring in the clavam and carbapenem antibiotics. β‐LS catalyzes a two‐stage reaction in which N2‐(2‐carboxyethyl)‐L‐arginine is first adenylated, and then undergoes intramolecular ring closure. It was previously shown that the forward kinetic commitment to β‐lactam formation is high, and that the overall rate of reaction is partially limited to a protein conformational change rather than to the chemical step alone of closing the strained ring. β‐Lactam formation was evaluated on the basis of X‐ray crystal structures, site‐specific mutation, and kinetic and computational studies. The combined evidence clearly points to a reaction coordinate involving the formation of a tetrahedral transition state/intermediate stabilized by a conserved Lys. The combination of substrate preorganization, a well‐stabilized transition state and an excellent leaving group facilitates this acyl substitution to account for the strong forward commitment to catalysis and to lower the barrier of four‐membered ring formation to the magnitude of a protein conformational change.
Plasticity changes in the brain in hypnosis and meditation
Authors: Halsband Ulrike , Mueller Susanne , Hinterberger Thilo , Strickner Simon
Published: October 2009

Neuroscientific evidence interprets both hypnotic trance induction and different meditation traditions as modified states of consciousness that emphasize attention, concentration and the letting go of thoughts, but they differ in terms of sensory input, processing, memory, and the sense of time. Furthermore, hypnosis is based on the suggestibility of a person and meditation on mindfulness; therefore it is not surprising to find differential brain plasticity changes. We analysed shared and non‐shared neural substrates using electroencephalography (EEG), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). Most pronounced EEG changes were in deep as compared to light hypnosis (step‐by‐step induction) and in arm levitation where suggested movement was perceived as external. In a within‐subject‐design changes in brain activity during hypnosis and Tibetan Buddhist meditation were compared. High amplitudes in alpha frequency bands were most pronounced with meditation at frontal positions and with hypnosis in central and temporal locations. Significantly greater activity in theta 2 band was observed only with hypnosis in both hemispheres. PET cerebral activation patterns of imagery‐mediated learning were analysed in hypnosis in a within‐subject‐design. Compared with baseline the learning of high‐imagery words was associated with (i) more pronounced bilateral activation in the occipital cortex and prefrontal areas and (ii) improved memory performance. Visual illusion in hypnosis was studied with fMRI, analysed with Granger Causality Mapping, showing changes in the effective connectivity relations of fusiform gyrus, anterior cingulate cortex and intraparietal sulcus. Little is known about the neurobiological basis of theprocessof enhancing cognitive and emotional traits in meditation. In a longitudinal fMRI study attention abilities through intensive Soto‐Zen meditation were investigated before (baseline), after training (6 months) and at follow‐up (9 months). After six months differences were observed in the left inferior and left superior frontal gyrus; after 9 months activations in the left precuneus. Taken together, the findings advance understanding of the neural mechanisms that underlie hypnosis and meditation. Further studies with a greater sample size are needed to explore the differences and commonalities of hypnosis and different meditation techniques. Copyright © 2009 British Society of Experimental & Clinical Hypnosis. Published by John Wiley & Sons, Ltd.
Total Synthesis and Biological Evaluation of (+)‐Neopeltolide and Its Analogues
Authors: Fuwa Haruhiko , Saito Asami , Naito Shinya , Konoki Keiichi , Yotsu‐Yamashita Mari , Sasaki Makoto
Published: October 2009

The stereocontrolled total synthesis of the originally proposed (1) and correct (2) structures of (+)‐neopeltolide, a novel marine macrolide natural product with highly potent antiproliferative activity against several cancer cell lines as well as potent antifungal activity, has been achieved by exploiting a newly developed Suzuki–Miyaura coupling/ring‐closing metathesis strategy. Alkylborate 44, which was generated in situ from iodide 34, was coupled with enol phosphate 8 by a Suzuki–Miyaura coupling. Ring‐closing metathesis of the derived diene 45 followed by stereoselective hydrogenation afforded tetrahydropyran 47 as a single stereoisomer in high overall yield from 34. Our convergent strategy enabled us to construct the 14‐membered macrolactone core structure of 2 in a rapid and efficient manner. Total synthesis and biological evaluation of synthetic intermediates and designed synthetic analogues, performed to establish the structure–activity relationships of 2, led to the discovery of a structurally simple yet potent cytotoxic analogue, 9‐demethylneopeltolide (54).
A Unidirectional Open–Close Mechanism of Metal‐Ion‐Driven Molecular Hinges with Adjustable Amplitude
Authors: Ernst Silvia , Haberhauer Gebhard
Published: October 2009

A basic requirement for each molecular system that is supposed to perform work is a synchronized and unidirectional movement. Unidirectionality can be achieved by a change of configuration or conformation that is controllable by external stimulation. Molecular hinges based on a bipyridine unit work unidirectionally and are able to reach an amplitude of motion that amounts to about 180°. To analyze if it is possible to adjust the height of the unidirectional amplitude of motion, three planar chiral molecular hinge systems with a 2,2′‐bipyridine unit as functional element were designed and stimulated with various divalent metal ions in different solvents. The configurations of the hinges were determined by DFT calculations using B3LYP and the 6‐31G* basis set and experimentally verified by 2D NMR NOESY spectra. Circular dichroism (CD) and UV spectroscopy were used to study the properties of the hinges by the addition of metal ions (primarily Zn2+ and Hg2+) in dichloromethane and methanol. The choice of metal ions and solvents determines whether or not and how far the hinges are closed. Furthermore, a drastic change in the height of the amplitude of motion can be reached by modifying the position of the bipyridine unit in the hinge. Amplitude values from 45 up to 190° were obtained from quantum mechanical calculations. This control of the amplitude of motion can in the future be used for more complex switching processes of molecular machines.
Preparation of Ni/TiO2 Nanoparticles and Their Catalytic Performance on the Thermal Decomposition of Ammonium Perchlorate
Authors: Li Cheng , Ma Zhenye , Zhang Lixiong , Qian Renyuan
Published: October 2009

Metal/oxide nanoparticles are attractive because of their special structure and better properties. The Ni/TiO2 nanoparticles were prepared by a liquid phase chemical reduction method in this paper. The obtained‐products were characterized by inductively coupled plasma (ICP), X‐ray diffraction (XRD), high‐resolution transmission electron microscopy (HRTEM) and scanning electron microscopy (SEM). The results show that Ni particles in Ni/TiO2 nanoparticles exhibit better dispersion and the size of most Ni particles is 10 nm or so. The catalytic activity of Ni/TiO2 nanoparticles on the thermal decomposition of ammonium perchlorate (AP) was investigated by simultaneous thermogravimetry and differential thermal analysis (TG‐DTA). Results show that composite process of Ni and TiO2 can improve the catalytic activity of Ni nanoparticles on the thermal decomposition of AP, which is mainly attributed to the improvement of Ni dispersion in Ni/TiO2 nanoparticles. The catalytic activity of Ni/TiO2 nanoparticles increases with increasing the weight ratio of Ni to AP.
Synthesis and Characterization of Imidacloprid/Hydrotalcite‐like Compound Nanohybrids
Authors: Qiu Depeng , Hou Wanguo , Xu Jie , Liu Jianqiang , Liu Shaojie
Published: October 2009

Hydrotalcite‐like compounds (HTlc) were first modified by sodium dodecyl sulfate (SDS), then the intercalation of imidacloprid (IM) into modified HTlc was carried out in mixed solvent of toluene/ethanol by an evaporating solvent enhanced intercalation method, obtaining IM‐SDS‐HTlc nanohybrids. It was found that the nanohybrids could well control the release of imidacloprid, demonstrating that the nanohybrids are a potential pesticide controlled‐release formulation. The release of imidacloprid from IM‐SDS‐HTlc nanohybrids is dependent on the pH and the presence of electrolyte in release medium. Acidic medium and the presence of electrolytes induce the higher release rate of imidacloprid. The release process of imidacloprid from IM‐SDS‐HTlc nanohybrids can be described by pseudo‐second‐order release kinetics.
Theoretical Investigation on Electronic Transition of Tris(8‐quinolinolate) Aluminum Grafted on Poly(p‐phenylenevinylene) Units with the Localized‐density‐matrix Method
Authors: Sun Gang , Zhang Min , Yang Guochun , Zhao Liang , Fu Qiang , Su Zhongmin
Published: October 2009

An unsystematic molecule PPV‐Alq3 [3‐(4‐((E)‐2‐(8‐hydroxy‐3‐(4‐styrylstyryl)quinolin‐Alq2‐6‐yl)vinyl)‐ styryl)‐6‐(4‐styrylstyryl)quinolin‐8‐olate‐Alq2; q=8‐quinolinolate], which combines poly(p‐phenylenevinylene) with tris(8‐quinolinolate)aluminum, has been studied using a localized‐density‐matrix method. The absorption spectra and electronic transition properties were analyzed and compared with both intermediate neglect of the differential overlap method and the localized‐density‐matrix method. Great efforts have been made on investigating conjugated system on the absorption properties as these can be particularly important for many applications. Two different absorptions of the special molecule, tris(8‐quinolinolate)aluminum grafted on poly(p‐phenylenevinylene) units, were further discussed with density matrices. For the molecule, the first absorption peak is at 413 nm near the purple light. Two 8‐hydroxyquinolines have very slight electronic transition properties. Another absorption peak is at 237 nm. The second characteristic peak of molecule is completely different from that of the first one, which comes from contribution of 8‐hyroxyquinolines in the two different side chains. Our studies show that electronic transition properties of poly(p‐phenylenevinylene) can be effectively tuned by grafting tris(8‐quinolinolate)‐aluminum on poly(p‐phenylenevinylene) from the standpoint of transition energies, frontier molecular orbitals and density matrices.
Excited State Intramolecular Proton Transfer in Methyl and Methoxy Substituted Salicylic Acid
Authors: Suban Kumar Sahoo , Rati Kanta Bera , Bikram Kishore Kanungo , Minati Baral
Published: October 2009

The excited state intramolecular proton transfer (ESIPT) processes in 3‐methylsalicyclic acid (3‐MeSA) and 3‐methoxysalicyclic acid (3‐MeOSA) have been investigated in cyclohexane medium by emission spectroscopic techniques. The ESIPT process was characterized in 3‐MeSA from the large Stokes fluorescent band (455 nm), but it was suppressed by 3‐MeOSA in cyclohexane. The ESIPT process was found to be accelerated both in 3‐MeSA and 3‐MeOSA in the presence of a hydrogen bond accepting agent, triethylamine (TEA). Further, theoretical calculations were carried out at the ground and excited states to complement the experimental evidences.
One‐pot Synthesis of 1,8‐Dioxo‐decahydroacridine Derivatives in Aqueous Media
Authors: Balalaie Saeed , Chadegani Fatemeh , Darviche Fatemeh , Bijanzadeh Hamid Reza
Published: October 2009

A new and efficient method for the synthesis of 1,8‐dioxo‐9‐aryl‐decahydroacridine derivatives was developed via a one‐pot three component reaction of dimedone, aromatic aldehydes and ammonium acetate in the presence of ammonium chloride, or Zn(OAc)2·2H2O or L‐proline separately in water in the short period of time and high yields.
A Facile Synthesis of N‐Aryl Substituted Piperidones
Authors: Geng Qian , Zhang Hui , Cao Weiguo , Chen Yali
Published: October 2009

A general and efficient procedure for the synthesis of N‐aryl‐substituted 4‐piperidones was developed. The two step syntheses proceeded with an overall yield of 60%‐83% using L‐proline as the ligand for the Cu(I)‐catalyzed Ullmann amination followed by subsequent hydrolysis of resulting ketals.
Enantioselective Alkynylzinc Addition to Carbonyl Compounds by Tf‐based Sulfamide‐amine Alcohol Catalysis
Authors: Li Hongwang , Li Xincheng , Xue Feng , Huang Yongbo , Jin Wei , Wan Boshun
Published: October 2009

The new Tf‐based sulfamide‐amine alcohol 3a was found to be very effective in catalyzing the enantioselective alkynylzinc addition to both aromatic aldehydes and unactivated aromatic ketones without using another metal species under mild condition, providing up to 92% ee and 90% ee for aldehydes and ketones, respectively.
Stereoselective Synthesis of Tetrahydropyran D‐Ring of Methyl Sartortuoate
Authors: Yao Hequan , Gao Yuan , Liu Peng , Xu Xingxiang
Published: October 2009

A stereoselective synthesis of functionalized tetrahydropyran D‐ring of methyl sartortuoate (1) was achieved starting from geraniol in a high yield. Sharpless asymmetric kinetic resolution, asymmetric dihydroxylation as well as asymmetric epoxidation were applied as key steps to establish all the four stereocenters of the D‐ring.
High‐performance Liquid Chromatography Study of the Nitration Course of Tetrabutoxycalix[4]arene at the Upper Rim: Determination of the Optimum Conditions for the Preparation of 5,11,17‐Trinitro‐25,26,27,28‐tetrabutoxycalix[4]arene
Authors: Li Zhengyi , Ma Jiejie , Chen Jiawen , Pan Yi , Qiang Juli , Wang Leyong
Published: October 2009

A selective nitration of calix[4]arene at the upper rim in one pot process was described by monitoring the time dependence of the distribution of products by high‐performance liquid chromatography (HPLC). The discrimination of five nitrated products was accomplished by molecular symmetry considerations and 1H NMR analysis. As a result, unusual 5,11,17‐trinitrocalix[4]arene (2d) was obtained in 57% isolated yield. 5,11‐Dinitro‐calix[4]arene (2b) and 5,11,17‐trinitrocalix[4]arene (2d) with tetranitrocalix[4]arene 2e were further characterized by crystal X‐ray diffraction analysis. Furthermore, as an example of potential application, trinitrocalix[4]arene 2d could be converted to triaminocalix[4]arene 3d conveniently.
Lanthanide Amide‐catalyzed Aza‐Henry Reaction of N‐Tosyl Imines with Nitroalkanes
Authors: Zhang Lijun , Wu Hongping , Su Shunpeng , Wang Shaowu
Published: October 2009

In the presence of 10 mol% lanthanide amide [(Me3Si)2N]3Ln(µ‐Cl)Li(THF)3, the aza‐Henry reaction of N‐tosyl imines with nitroalkanes (1:5 molar ratio) could be performed in good yields. The lanthanide amide‐catalyzed aza‐Henry reaction has the features of mild reaction conditions, tolerance of a variety of aromatic aldehyde‐derived imines and nitroalkanes, short time and good chemical yields. A catalytic mechanism for the reaction was also proposed.