bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase transition and ferroelectric properties of epitaxially strained KNbO3/NaNbO3 superlattice
Authors: Li Zhanfang , Lü Tianquan , Cao Wenwu
Published: December 2008

The influence of epitaxial strain on the crystal structure and polarization of KNbO3/NaNbO3 (KNO/NNO) superlattice has been quantified using density functional theory based on pseudopotential and plane-wave basis. A sequence of structural phase transitions with changing the in-plane misfit strain has been identified. If the compressive strain is more than −0.8%, tetragonal phase with polarization along [001] is stable. For the misfit strain between −0.8% and 0.36%, the stable phase is monoclinic while the stable phase becomes orthorhombic with polarization along [110] when the tensile strain is more than 0.36%. The spontaneous polarization in the orthorhombic phase reaches more than 70 μC/cm2.
Infrared spectroscopic methods for the study of aerosol particles using White cell optics: Development and characterization of a new aerosol flow tube
Authors: Nájera Juan J. , Fochesatto Javier G. , Last Deborah J. , Percival Carl J. , Horn Andrew B.
Published: December 2008

A description of a new aerosol flow tube apparatus for measurements in situ under atmospherically relevant conditions is presented here. The system consists of a laboratory-made nebulizer generation system and a flow tube with a White cell-based Fourier transform IR for the detection system. An assessment of the White cell coupled to the flow tube was carried out by an extensive set of experiments to ensure the alignment of the infrared beam and optimize the performance of this system. The detection limit for CO was established as (1.0±0.3) ppm and 16 passes was chosen as the optimum number of passes to be used in flow tube experiments. Infrared spectroscopy was used to characterize dry aerosol particles in the flow tube. Pure particles composed of ammonium sulfate or sodium chloride ranging between 0.8 and 2.1 μm for size diameter and (0.8–4.9)×106 particles/cm3 for density number were generated by nebulization of aqueous solutions. Direct measurements of the aerosol particle size agree with size spectra retrieved from inversion of the extinction measurements using Mie calculations, where the difference residual value is in the order of 0.2%. The infrared detection limit for ammonium sulfate aerosol particles was determined as dp=0.9 μm and N=5×103 particles/cm3 with σ=1.1 by Mie calculation. Alternatively, Mie calculations were performed to determine the flexibility in varying the optical length when aerosol particles are sent by the injector. The very good agreement between the values retrieved for aerosol particles injected through the flow tube or through the injector clearly validates the estimation of the effective optical path length for the injector. To determine the flexibility in varying the reaction zone length, analysis of the extinction spectra as function of the position of the injector was carried out by monitoring the integrated area of different absorption modes of the ammonium sulfate. We conclude that the aerosol loss in the flow tube reactor is negligible and that the aerosol particles remain on-axis for the length of the flow tube.
Intracavity terahertz generation inside a high-energy ultrafast soliton fiber laser
Authors: Matthäus Gabor , Ortaç Bülend , Limpert Jens , Nolte Stefan , Hohmuth Rico , Voitsch Martin , Richter Wolfgang , Pradarutti Boris , Tünnermann Andreas
Published: December 2008

Intracavity terahertz emission inside a high-energy ultrafast Yb-doped fiber laser is presented. The terahertz radiation is generated by a transient photocurrent induced at the surface of a saturable InGaAs multiquantum well grown by molecular beam epitaxy on top of a semiconductor Bragg reflector. This device simultaneously works as the saturable absorber mirror for initiating and managing the passive mode locking required for the ultrashort pulse operation of the laser system. The maximum terahertz average power achieved is 4.2μW, which reveals a net conversion efficiency of 3.1×10−5.
Botulinum toxin detection using AlGaN∕GaN high electron mobility transistors
Authors: Wang Yu-Lin , Chu B. H. , Chen K. H. , Chang C. Y. , Lele T. P. , Tseng Y. , Pearton S. J. , Ramage J. , Hooten D. , Dabiran A. , Chow P. P. , Ren F.
Published: December 2008

Antibody-functionalized, Au-gated AlGaN∕GaN high electron mobility transistors (HEMTs) were used to detect botulinum toxin. The antibody was anchored to the gate area through immobilized thioglycolic acid. The AlGaN∕GaN HEMT drain-source current showed a rapid response of less than 5s when the target toxin in a buffer was added to the antibody-immobilized surface. We could detect a range of concentrations from 1to10ng∕ml. These results clearly demonstrate the promise of field-deployable electronic biological sensors based on AlGaN∕GaN HEMTs for botulinum toxin detection.
Correspondence of the sign change in organic magnetoresistance with the onset of bipolar charge transport
Authors: Bloom F. L. , Wagemans W. , Kemerink M. , Koopmans B.
Published: December 2008

In this work we examine the transition between positive and negative organic magnetoresistance in poly[2-methoxy-5-(3′, 7′-dimethyloctyloxy)-p-phenylenevinylene] in order to understand how different regimes of charge transport affect the organic magnetoresistance effect. To characterize the charge transport in these devices we measured the current, low frequency differential capacitance, and electroluminescence efficiency as a function of voltage. These measurements show that the sign change of the magnetoresistance corresponds with a change from a unipolar diffusive transport below the built in voltage (Vbi) to a regime of bipolar drift transport above Vbi.
Terahertz Si:B blocked-impurity-band detectors defined by nonepitaxial methods
Authors: Rauter P. , Fromherz T. , Winnerl S. , Zier M. , Kolitsch A. , Helm M. , Bauer G.
Published: December 2008

The molecular beam epitaxial (MBE) fabrication of blocked-impurity-band detectors (BIB) has been a technologically complex and delicate matter ever since its demonstration in silicon, and has not been adapted for other material systems offering detection onsets at lower terahertz frequencies. We report the fabrication and characterization of a vertical Si:B BIB, circumventing the intrinsically troublesome MBE growth of an ultrapure blocking layer by employing ion implantation. We present a thorough characterization of our device, which exhibits highly competitive figures of merits. Our results not only increase the accessibility of BIB fabrication tools for ultrasensitive terahertz detection but also open a road to other material systems.
PKCη regulates occludin phosphorylation and epithelial tight junction integrity
Authors: Suzuki Takuya , Elias Bertha C. , Seth Ankur , Shen Le , Turner Jerrold R. , Giorgianni Francesco , Desiderio Dominic , Guntaka Ramareddy , Rao Radhakrishna
Published: December 2008

PKCη is expressed predominantly in the epithelial tissues; however, its role in the regulation of epithelial tight junctions (TJs) is unknown. We present evidence that PKCη phosphorylates occludin on threonine residues (T403 and T404) and plays a crucial role in the assembly and/or maintenance of TJs in Caco-2 and MDCK cell monolayers. Inhibition of PKCη by specific pseudo substrate inhibitor or knockdown of PKCη by specific shRNA disrupts the junctional distribution of occludin and ZO-1 and compromises the epithelial barrier function. Expression of dominant negative, PKCη
K394R
disrupts the TJ and barrier function, whereas wild-type PKCη and constitutively active PKCη
A161E
enhance the TJ integrity. Inhibition and knockdown of PKCη or expression of PKCη
K394R
induce dephosphorylation of occludin on threonine residues, whereas active PKCη elevates occludin phosphorylation. PKCη directly interacts with the C-terminal domain of occludin and phosphorylates it on highly conserved T403 and T404. T403/404A mutations result in the loss of occludin's ability to localize at the TJs, whereas T403/404D mutations attenuates the PKCη inhibitor-mediated redistribution of occludin from the intercellular junctions. These results reveal an important mechanism of epithelial TJ regulation by PKCη.
Force generation by a dynamic Z-ring in
Escherichia coli
cell division
Authors: Allard Jun F. , Cytrynbaum Eric N.
Published: December 2008

FtsZ, a bacterial homologue of tubulin, plays a central role in bacterial cell division. It is the first of many proteins recruited to the division site to form the Z-ring, a dynamic structure that recycles on the time scale of seconds and is required for division to proceed. FtsZ has been recently shown to form rings inside tubular liposomes and to constrict the liposome membrane without the presence of other proteins, particularly molecular motors that appear to be absent from the bacterial proteome. Here, we propose a mathematical model for the dynamic turnover of the Z-ring and for its ability to generate a constriction force. Force generation is assumed to derive from GTP hydrolysis, which is known to induce curvature in FtsZ filaments. We find that this transition to a curved state is capable of generating a sufficient force to drive cell-wall invagination in vivo and can also explain the constriction seen in the in vitro liposome experiments. Our observations resolve the question of how FtsZ might accomplish cell division despite the highly dynamic nature of the Z-ring and the lack of molecular motors.
Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment
Authors: Albanesi Cristina , Scarponi Claudia , Pallotta Sabatino , Daniele Roberta , Bosisio Daniela , Madonna Stefania , Fortugno Paola , Gonzalvo-Feo Safiyè , Franssen Jean-Denis , Parmentier Marc , De Pità Ornella , Girolomoni Giampiero , Sozzani Silvano
Published: December 2008

Psoriasis is a type I interferon-driven T cell–mediated disease characterized by the recruitment of plasmacytoid dendritic cells (pDC) into the skin. The molecules involved in pDC accumulation in psoriasis lesions are unknown. Chemerin is the only inflammatory chemotactic factor that is directly active on human blood pDC in vitro. The aim of this study was to evaluate the role of the chemerin/ChemR23 axis in the recruitment of pDC in psoriasis skin. Prepsoriatic skin adjacent to active lesions and early lesions were characterized by a strong expression of chemerin in the dermis and by the presence of CD15+ neutrophils and CD123+/BDCA-2+/ChemR23+ pDC. Conversely, skin from chronic plaques showed low chemerin expression, segregation of neutrophils to epidermal microabscesses, and few pDC in the dermis. Chemerin expression was localized mainly in fibroblasts, mast cells, and endothelial cells. Fibroblasts cultured from skin of psoriatic lesions expressed higher levels of chemerin messenger RNA and protein than fibroblasts from uninvolved psoriatic skin or healthy donors and promoted pDC migration in vitro in a chemerin-dependent manner. Therefore, chemerin expression specifically marks the early phases of evolving skin psoriatic lesions and is temporally strictly associated with pDC. These results support a role for the chemerin/ChemR23 axis in the early phases of psoriasis development.
A role for the IgH intronic enhancer Eμ in enforcing allelic exclusion
Authors: Li Fubin , Eckhardt Laurel A.
Published: December 2008

The intronic enhancer (Eμ) of the immunoglobulin heavy chain (IgH) locus is critical for V region gene assembly. To determine Eμ's subsequent functions, we created an Igh allele with assembled VH gene but with Eμ removed. In mice homozygous for this Eμ-deficient allele, B cell development was normal and indistinguishable from that of mice with the same VH knockin and Eμ intact. In mice heterozygous for the Eμ-deficient allele, however, allelic exclusion was severely compromised. Surprisingly, this was not a result of reduced suppression of V-DJ assembly on the second allele. Rather, the striking breakdown in allelic exclusion took place at the pre-B to immature B cell transition. These findings reveal both an important role for Eμ in influencing the fate of newly arising B cells and a second checkpoint for allelic exclusion.
Natural agonists for aryl hydrocarbon receptor in culture medium are essential for optimal differentiation of Th17 T cells
Authors: Veldhoen Marc , Hirota Keiji , Christensen Jillian , O'Garra Anne , Stockinger Brigitta
Published: December 2008

Th17 cell differentiation is dependent on interleukin (IL)-6 and transforming growth factor (TGF)-β, and it is modulated by activation of the aryl hydrocarbon receptor (AhR). In this study, we show that differentiation of Th17 cells, but not Th1 or induced regulatory T (iT reg) cells, is increased by endogenous AhR agonists present in culture medium. Th17 development from wild-type mice is suboptimal in the presence of the AhR antagonist CH-223191, similar to the situation in AhR-deficient mice, which show attenuated IL-17 production and no IL-22 production. The presence of natural AhR agonists in culture medium is also revealed by the induction of CYP1A1, a downstream target of AhR activation. However, the most commonly used medium, RPMI, supports very low levels of Th17 polarization, whereas Iscove's modified Dulbecco's medium, a medium richer in aromatic amino acids, which give rise to AhR agonists, consistently results in higher Th17 expansion in both mouse and human cells. The relative paucity of AhR agonists in RPMI medium, coupled with the presence of factors conducive to IL-2 activation and enhanced Stat5 phosphorylation, conspire against optimal Th17 differentiation. Our data emphasize that AhR activation plays an essential part in the development of Th17 cells and provide a rational explanation for the poor in vitro polarization of Th17 cells that is reported in the majority of publications for both mouse and human cells.
Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor
Authors: Mori Yasuo , Iwasaki Hiromi , Kohno Kentaro , Yoshimoto Goichi , Kikushige Yoshikane , Okeda Aki , Uike Naokuni , Niiro Hiroaki , Takenaka Katsuto , Nagafuji Koji , Miyamoto Toshihiro , Harada Mine , Takatsu Kiyoshi , Akashi Koichi
Published: December 2008

To establish effective therapeutic strategies for eosinophil-related disorders, it is critical to understand the developmental pathway of human eosinophils. In mouse hematopoiesis, eosinophils originate from the eosinophil lineage-committed progenitor (EoP) that has been purified downstream of the granulocyte/macrophage progenitor (GMP). We show that the EoP is also isolatable in human adult bone marrow. The previously defined human common myeloid progenitor (hCMP) population (Manz, M.G., T. Miyamoto, K. Akashi, and I.L. Weissman. 2002. Proc. Natl. Acad. Sci. USA. 99:11872–11877) was composed of the interleukin 5 receptor α chain+ (IL-5Rα+) and IL-5Rα− fractions, and the former was the hEoP. The IL-5Rα+CD34+CD38+IL-3Rα+CD45RA− hEoPs gave rise exclusively to pure eosinophil colonies but never differentiated into basophils or neutrophils. The IL-5Rα− hCMP generated the hEoP together with the hGMP or the human megakaryocyte/erythrocyte progenitor (hMEP), whereas hGMPs or hMEPs never differentiated into eosinophils. Importantly, the number of hEoPs increased up to 20% of the conventional hCMP population in the bone marrow of patients with eosinophilia, suggesting that the hEoP stage is involved in eosinophil differentiation and expansion in vivo. Accordingly, the phenotypic definition of hCMP should be revised to exclude the hEoP; an “IL-5Rα–negative” criterion should be added to define more homogenous hCMP. The newly identified hEoP is a powerful tool in studying pathogenesis of eosinophilia and could be a therapeutic target for a variety of eosinophil-related disorders.
Local Anesthetics Disrupt Energetic Coupling between the Voltage-sensing Segments of a Sodium Channel
Authors: Muroi Yukiko , Chanda Baron
Published: December 2008

Local anesthetics block sodium channels in a state-dependent fashion, binding with higher affinity to open and/or inactivated states. Gating current measurements show that local anesthetics immobilize a fraction of the gating charge, suggesting that the movement of voltage sensors is modified when a local anesthetic binds to the pore of the sodium channel. Here, using voltage clamp fluorescence measurements, we provide a quantitative description of the effect of local anesthetics on the steady-state behavior of the voltage-sensing segments of a sodium channel. Lidocaine and QX-314 shifted the midpoints of the fluorescence–voltage (F-V) curves of S4 domain III in the hyperpolarizing direction by 57 and 65 mV, respectively. A single mutation in the S6 of domain IV (F1579A), a site critical for local anesthetic block, abolished the effect of QX-314 on the voltage sensor of domain III. Both local anesthetics modestly shifted the F-V relationships of S4 domain IV toward hyperpolarized potentials. In contrast, the F-V curve of the S4 domain I was shifted by 11 mV in the depolarizing direction upon QX-314 binding. These antagonistic effects of the local anesthetic indicate that the drug modifies the coupling between the voltage-sensing domains of the sodium channel. Our findings suggest a novel role of local anesthetics in modulating the gating apparatus of the sodium channel.
The effects of perceived predation risk on pre‐ and post‐metamorphic phenotypes in the common frog
Authors: Stamper C. E. , Downie J. R. , Stevens D. J. , Monaghan P.
Published: December 2008

Where organisms undergo radical changes in habitat during ontogeny, dramatic phenotypic reshaping may be required. However, physiological and functional interrelationships may constrain the extent to which an individual's phenotype can be equally well adapted to their habitat throughout the life cycle. The phenotypic response of tadpoles to the presence of a predator has been reported for several species of anuran but the potential post‐metamorphic consequences have rarely been considered. We reared common frog Rana temporaria tadpoles in the presence or absence of a larval odonate predator, Aeshna juncea, and examined the consequences of the resulting phenotypic adjustment in the aquatic larval stage of the life cycle for the terrestrial juvenile phenotype. In early development tadpoles developed deeper tail fins and muscles in response to the predator and, in experimental trials, swam further than those reared in the absence of a predator. While the difference in swimming ability remained significant throughout the larval period, by the onset of metamorphosis we could no longer detect any differences in the morphological parameters measured. The corresponding post‐metamorphic phenotypes also did not initially differ in terms of morphology. At 12 weeks post‐metamorphosis, however, froglets that developed from predator‐exposed tadpoles swam more slowly and less far than those that developed from tadpoles reared in the absence of predators, the opposite trend to that observed in the larval stage of the life cycle, and had narrower femurs. These results suggest that there may be long‐term costs for subsequent life‐history stages of tailoring the larval phenotype to prevailing environmental conditions.
Ambush site selection and ontogenetic shifts in foraging strategy in a semi‐aquatic pit viper, the Eastern cottonmouth
Authors: Eskew E. A. , Willson J. D. , Winne C. T.
Published: December 2008

Although habitat selection has been studied in a variety of snake taxa, little is known about habitat selection in aquatic snake species. Additionally, due to their small size and secretive nature, juvenile snakes are seldom included in habitat selection studies. The Eastern cottonmouth Agkistrodon piscivorus is a semi‐aquatic pit viper known to use ambush, sit‐and‐wait foraging strategies. Ambush hunters are likely to select habitats that increase opportunity for successful prey capture while minimizing predation risk and maintaining appropriate thermal and hydric conditions. We characterized the foraging strategy and microhabitat use of cottonmouths at Ellenton Bay, an isolated Carolina bay freshwater wetland on the Savannah River Site in SC, USA. We measured habitat characteristics of 55 ambush sites used by 51 individual cottonmouths located during nighttime visual surveys, as well as 225 randomly selected sites within our search area. Cottonmouths exhibited an ontogenetic shift in foraging strategy with juveniles using predominately ambush foraging around the edge of the wetland while adults were most often encountered actively moving within the wetland. Principal components analysis revealed that juveniles selected foraging microhabitats that were different from random and consisted of mud substrate with sparse vegetation, whereas adults occupied a greater variety of microhabitats that did not differ from random. Concomitantly, free‐ranging cottonmouths exhibited ontogenetic shifts in diet: juveniles consumed mostly salamanders, while adults ate a greater variety of prey including other snakes and birds. Our results highlight the importance of understanding how ontogenetic changes in coloration, diet and predation risk influence foraging strategy and microhabitat selection in snakes.
Wnt signalling in mouse mesenchymal stem cells: impact on proliferation, invasion and MMP expression
Authors: Karow Marisa , Popp Tanja , Egea Virginia , Ries Christian , Jochum Marianne , Neth Peter
Published: December 2008

Based on the capacity of mesenchymal stem cells (MSC) to differentiate into multiple cell types in vitro and in vivo, MCS may be a suitable source for cell therapy and regeneration strategies. A prerequisite for effective clinical applications of human MSC (hMSC) is a profound knowledge of signal transduction cascades that mediate processes like proliferation, targeted migration and differentiation. Recently, we identified the canonical Wnt signal transduction pathway as a key player in hMSC proliferation and invasion. To evaluate whether those findings are transferable to the equivalent counterparts in mice, we studied important steps in the wingless/int‐1 (Wnt) signal transduction pathway in mouse MSC (mMSC) and mMSC carrying a T cell specific transcription factor (TCF)/lymphoid enhancer binding factor (LEF)‐reporter transgene. We found that the induction of the canonical Wnt pathway resulted in the up‐regulation of the known Wnt target gene cyclin D1, closely associated with an enhanced proliferation capacity of mMSC. Interestingly, the expression of the Wnt target gene membrane type 1‐matrix metalloproteinase (MT1‐MMP) was diminished in mMSC upon Wnt3a stimulation, which came along with an impaired invasion. In line with these findings, MMP‐2 and MMP‐9 expression levels in mMSC were also decreased after Wnt3a treatment. In contrast, inhibition of Wnt signalling by the knockdown of the transcriptional activator β‐catenin resulted in an up‐regulation of MT1‐MMP and mMSC invasion. By comparing these findings with the settings in hMSC, major differences in Wnt‐regulated MMP expression were observed in mMSC. Thus, our data advice caution when mouse model systems represent the pre‐clinical validation of MSC‐mediated therapeutical approaches.
Crocetin protects against cardiac hypertrophy by blocking MEK‐ERK1/2 signalling pathway
Authors: Cai Jun , Yi Fang‐Fang , Bian Zhou‐Yan , Shen Di‐Fei , Yang Long , Yan Ling , Tang Qi‐Zhu , Yang Xin‐Chun , Li Hongliang
Published: December 2008

Oxidative stress plays a critical role in the progression of pathological cardiac hypertrophy and heart failure. Because crocetin represses oxidative stress in vitro and in vivo, we have suggested that crocetin would repress cardiac hypertrophy by targeting oxidative stress‐dependent signalling. We tested this hypothesis using primary cultured cardiac myocytes and fibroblasts and one well‐established animal model of cardiac hypertrophy. The results showed that crocetin (1–10 μM) dose‐dependently blocked cardiac hypertrophy induced by angiogensin II (Ang II; 1 μM) in vitro. Our data further revealed that crocetin (50 mg/kg/day) both prevented and reversed cardiac hypertrophy induced by aortic banding (AB), as assessed by heart weight/body weight and lung weight/body weight ratios, echocardio‐graphic parameters and gene expression of hypertrophic markers. The inhibitory effect of crocetin on cardiac hypertrophy is mediated by blocking the reactive oxygen species (ROS)‐dependent mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated kinase‐1/2 (MEK/ERK1/2) pathway and GATA binding protein 4 (GATA‐4) activation. Further investigation demonstrated that crocetin inhibited inflammation by blocking nuclear factor kappa B (NF‐κB) signalling and attenuated fibrosis and collagen synthesis by abrogating MEK‐ERK1/2 signalling. Overall, our results indicate that crocetin, which is a potentially safe and inexpensive therapy for clinical use, has protective potential in targeting cardiac hypertrophy and fibrosis by suppression of ROS‐dependent signalling pathways.
A complex intronic enhancer regulates expression of the CFTR gene by direct interaction with the promoter
Authors: Ott Christopher J. , Suszko Magdalena , Blackledge Neil P. , Wright Jane E. , Crawford Gregory E. , Harris Ann
Published: December 2008

Genes can maintain spatiotemporal expression patterns by long‐range interactions between cis‐acting elements. The cystic fibrosis transmembrane conductance regulator gene (CFTR) is expressed primarily in epithelial cells. An element located within a DNase I‐hyper‐sensitive site (DHS) 10 kb into the first intron was previously shown to augment CFTR promoter activity in a tissue‐specific manner. Here, we reveal the mechanism by which this element influences CFTR transcription. We employed a high‐resolution method of mapping DHS using tiled microarrays to accurately locate the intron 1 DHS. Transfection of promoter‐reporter constructs demonstrated that the element displays classical tissue‐specific enhancer properties and can independently recruit factors necessary for transcription initiation. In vitro DNase I footprinting analysis identified a protected region that corresponds to a conserved, predicted binding site for hepatocyte nuclear factor 1 (HNF1). We demonstrate by electromobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) that HNF1 binds to this element both in vitro and in vivo. Moreover, using chromosome conformation capture (3C) analysis, we show that this element interacts with the CFTR promoter in CFTR‐expressing cells. These data provide the first insight into the three‐ dimensional (3D) structure of the CFTR locus and confirm the contribution of intronic cis‐acting elements to the regulation of CFTR gene expression.
Localized SDF‐1alpha gene release mediated by collagen substrate induces CD117+ stem cells homing
Authors: Wang Weiwei , Li Wenzhong , Ong Lee‐Lee , Furlani Dario , Kaminski Alexander , Liebold Andreas , Lützow Karola , Lendlein Andreas , Wang Jun , Li Ren‐Ke , Steinhoff Gustav , Ma Nan
Published: December 2008

Stromal cell‐derived factor‐1α (SDF‐1α) mediated mobilization and homing of stem cells showed promising potential in stem cell based tissue engineering and regenerative medicine. However local and sustained release of SDF‐1α is indispensable for stem cell mediated regenerative process due to its short half‐life under inflammatory conditions. In this study, a gene activated collagen substrate (GAC) was formed via assembly of plasmid encoding SDF‐1α into a collagen substrate to create a microenvironment favoring stem cell homing. Local release of SDF‐1α from the transfected cells on GAC and its effect on CD117+ stem cell homing were investigated. Non‐viral poly‐ethyleneimine (25kDa PEI)/DNA complexes were mixed with rat tail collagen solution to form the GAC. Optimization of GAC was carried out based on collagen effects on the PEI/DNA complexes, viability and luciferase expression of COS7 cells on GAC. CD117+ stem cells homing in response to SDF‐1α local expression from transfected cells on GAC were investigated in a flow chamber in vitro and in a mouse hind limb model in vivo. The gene expression, migration of CD117+ stem cells and the induced inflammation were investigated with immunostaining, reverse transcription polymerase chain reaction (RT‐PCR) and H&E staining. The optimized parameters for GAC were DNA dosage 10 μg/cm2, molar ratio of PEI nitrogen in primary amine to DNA phosphate (N/P ratio) 4 and mass ratio of collagen to DNA (C/D ratio) 1.0. It kept cell viability above 75% and transfection efficiency around 5.8 × 105 RLU/mg protein. GAC allowed the sustained gene release up to 60 days. GAC mediated SDF‐1α gene release induced migration and homing of CD117+ stem cells in vitro and in vivo significantly, and the inflammation of GAC reduced significantly two weeks after transplantation. GAC is a promising stem cell based therapeutic strategy for regenerative medicine.
Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma
Authors: Lawrie Charles H. , Chi Jianxiang , Taylor Stephen , Tramonti Daniela , Ballabio Erica , Palazzo Stefano , Saunders Nigel J. , Pezzella Francesco , Boultwood Jacqueline , Wainscoat James S. , Hatton Christian S. R.
Published: December 2008

MicroRNAs are naturally occurring small RNA species that regulate gene expression and are frequently abnormally expressed in cancers. However, the role of microRNAs in lymphoma is poorly understood. Therefore, we undertook a comprehensive study of microRNA expression in two of the most common lymphomas: diffuse large B‐cell lymphoma (DLBCL) (n= 80) and follicular lymphoma (FCL) (n= 18) using microarrays containing probes for 464 human microRNAs. Unsupervised cluster analysis revealed distinct expression patterns between these two lymphomas and specific microRNA signatures (including members of the miR‐17–92 cluster) were derived that correctly predicted lymphoma type in >95% of cases. Furthermore, we identified microRNAs in de novo DLBCL (n= 64) associated with germinal centre‐like and non‐germinal centre‐like immunophenotypes, international prognostic index status and event‐free survival in CHOP and rituximab (R)‐CHOP treated patients. Despite the indolent nature of FCL a significant proportion of cases undergo high‐grade transformation to more aggressive DLBCL. In order to see if transformation is associated with changes in microRNA expression we compared transformed DLBCL cases (n= 16) with de novo DLBCL, as well as FCL cases that underwent subsequent transformation (n= 7) with FCL cases that had not transformed at a median follow‐up of 60 months (n= 11). Differential expression of 12 microRNAs correctly predicted >85% of transformed versus de novo DLBCL cases; six microRNAs (miR‐223, 217, 222, 221 and let‐7i and 7b) were found which could similarly predict or transformation in FCL (P< 0.05). These data suggest that microRNAs have potential as diagnostic and prognostic markers in these lymphomas and may be used to identify FCL patients at risk of high‐grade transformation.
Isolation and in vitro chondrogenic potential of human foetal spine cells
Authors: Quintin Aurelie , Schizas Constantin , Scaletta Corinne , Jaccoud Sandra , Gerber Stefan , Osterheld Maria‐Chiara , Juillerat Lucienne , Applegate Lee Ann , Pioletti Dominique P.
Published: December 2008

Cell therapy for nucleus pulposus (NP) regeneration is an attractive treatment for early disc degeneration as shown by studies using autologous NP cells or stem cells. Another potential source of cells is foetal cells. We investigated the feasibility of isolating foetal cells from human foetal spine tissues and assessed their chondrogenic potential in alginate bead cultures. Histology and immunohistochemistry of foetal tissues showed that the structure and the matrix composition (aggrecan, type I and II collagen) of foetal intervertebral disc (IVD) were similar to adult IVD. Isolated foetal cells were cultured in monolayer in basic media supplemented with 10% Fetal Bovine Serum (FBS) and from each foetal tissue donation, a cell bank of foetal spine cells at passage 2 was established and was composed of around 2000 vials of 5 million cells. Gene expression and immunohistochemistry of foetal spine cells cultured in alginate beads during 28 days showed that cells were able to produce aggrecan and type II collagen and very low level of type I and type X collagen, indicating chondrogenic differentiation. However variability in matrix synthesis was observed between donors. In conclusion, foetal cells could be isolated from human foetal spine tissues and since these cells showed chondrogenic potential, they could be a potential cell source for IVD regeneration.
Cellular repressor of E1A‐stimulated genes attenuates cardiac hypertrophy and fibrosis
Authors: Bian Zhouyan , Cai Jun , Shen Di‐fei , Chen Li , Yan Ling , Tang Qizhu , Li Hongliang
Published: December 2008

Cellular repressor of E1A‐stimulated genes (CREG) is a secreted glycoprotein of 220 amino acids. It has been proposed that CREG acts as a ligand that enhances differentiation and/or reduces cell proliferation. CREG has been shown previously to attenuate cardiac hypertrophy in vitro. However, such a role has not been determined in vivo. In the present study, we tested the hypothesis that overexpression of CREG in the murine heart would protect against cardiac hypertrophy and fibrosis in vivo. The effects of constitutive human CREG expression on cardiac hypertrophy were investigated using both in vitro and in vivo models. Cardiac hypertrophy was produced by aortic banding and infusion of angiotensin II in CREG transgenic mice and control animals. The extent of cardiac hypertrophy was quantitated by two‐dimensional and M‐mode echocardiography as well as by molecular and pathological analyses of heart samples. Constitutive over‐expression of human CREG in the murine heart attenuated the hypertrophic response, markedly reduced inflammation. Cardiac function was also preserved in hearts with increased CREG levels in response to hypertrophic stimuli. These beneficial effects were associated with attenuation of the mitogen‐activated protein kinase (MAPK)‐extracellular signal‐regulated kinase 1 (MEK‐ERK1)/2‐dependent signalling cascade. In addition, CREG expression blocked fibrosis and collagen synthesis through blocking MEK‐ERK1/2‐dependent Smad 2/3 activation in vitro and in vivo. Therefore, the expression of CREG improves cardiac functions and inhibits cardiac hypertrophy, inflammation and fibrosis through blocking MEK‐ERK1/2‐dependent signalling.
Slow and steady is the key to β‐cell replication
Authors: Brennand Kristen , Melton Doug
Published: December 2008

Diabetes is a chronic disease of failed glucose homeostasis

Structure and function of the adult pancreas

Diabetes is an attractive target for cellular replacement therapy

In vitro differentiation of β‐cells from embryonic stem cells

β‐cell maintenance and expansion

Strong evidence that new β‐cells come from old β‐cells

All β‐cells contribute equally to islet growth and maintenance

Putative pancreatic stem cells

Reported evidence for bone marrow stem cells giving rise to β‐cells

Reported evidence for spleen stem cells giving rise to β‐cells

Reported evidence for ductal stem cells giving rise to β‐cells

Reported evidence for acini stem cells giving rise to β‐cells

Reported evidence for islet and/or pancreatic stem cells giving rise to β‐cells

β‐cell turnover

β‐cell mass is dynamic

β‐cell replication changes with age

β‐cell replication increases during pregnancy

β‐cell replication increases in cases of increased blood glucose and/or insulin resistance

β‐cell replication is regulated by cell cycle genes

The elusive circulating β‐cell growth factor

Increasing β‐cell replication in vivo

In vitro culture of β‐cells

Summary

The β‐cells of the pancreas are responsible for insulin production and their destruction results in type I diabetes. β‐cell maintenance, growth and regenerative repair is thought to occur predominately, if not exclusively, through the replication of existing β‐cells, not via an adult stem cell. It was recently found that all β‐cells contribute equally to islet growth and maintenance. The fact that all β‐cells replicate homogeneously makes it possible to set up straightforward screens for factors that increase β‐cell replication either In vitro or in vivo. It is possible that a circulating factor may be capable of increasing β‐cell replication or that intrinsic cell cycle regulators may affect β‐cell growth. An improved understanding of the in vivo maintenance and growth of β‐cells will facilitate efforts to expand β‐cells In vitro and may lead to new treatments for diabetes.
The ethical use of plants in zoos: informing selection choices, uses and management strategies
Authors: FREDIANI K.
Published: December 2008

The modern zoo is one in a continual state of renewal, new developments being undertaken on a frequent basis to improve a site to benefit the many stakeholders, including animals, staff and visitors, and to maintain their continued support. Business development is also required to optimize the potential of a site to raise a surplus of cash to undertake important mission work including conservation. However, business growth to facilitate mission work presents an interesting dichotomy, one based around compromise borne from the need to undertake development to meet and exceed stringent welfare requirements and encourage visitors into a competitive market place for good days out. The potential ‘cost’ of the transaction business versus mission falls within the realm of managing and planning the zoo site itself, a cost that can impact beyond the borders of the site itself to include populations of flora and fauna that are affected by the management decisions made on site. These include populations of native species and their habitat but can also be considered to include wider environmental costs associated with trading where resources are brought in and have the potential to impact upon global habitats and threatened populations of species beyond the purely local scale. This can be a source of tension or conflict, a prerequisite to ethics. This paper reviews the conflict and the ethical choices that arise from plant procurement and use in zoos. It is concerned with providing (1) a framework based on optimizing potential and resolving conflict and (2) the provision of guidance to address issues of responsible personal conduct of those who are accountable for undertaking such services in zoos.
How can zoos import and display butterflies for educational purposes in a sustainable way?
Authors: VELTMAN K.
Published: December 2008

To display tropical butterflies and moths successfully zoos require energy‐consuming greenhouses capable of providing ideal environmental conditions, the presence of suitable plants for both general exhibition and for the provision of butterfly and caterpillar food, and large quantities of imported butterfly pupae. Many pupae originate from butterfly farms in Central and South America, Asia and Africa, where this business provides local people with a sustainable and profitable source of revenue. However, in these times of depleting resources the question is: how can zoos and butterfly breeders work together to improve the standards of sustainability throughout their industry? The way in which local people earn their livelihoods through butterfly farming is described. Suggestions are made regarding the reduction of energy costs of butterfly exhibits in Europe and the United States. Information is given about the great educational value of butterfly flight enclosures in zoos. The author visited several butterfly breeders in Costa Rica and researched the sustainability of keeping and breeding butterflies, both at breeding facilities in the tropics and in zoos in more temperate regions. Advice on how butterfly exhibits and the acquisition of pupae can become more sustainable and energy consumption can be reduced is also given.
Husbandry and breeding of Somali wild ass Equus africanus somalicus at Basel Zoo, Switzerland1
Authors: PAGAN O. , VON HOUWALD F. , WENKER C. , STECK B. L.
Published: December 2008

Little information is available in English on the keeping and breeding of the rarest equid species, the Critically Endangered Somali wild ass Equus africanus somalicus, in captivity. The husbandry experience gained by Basel Zoo over three decades of keeping this species is summarized with particular emphasis on management, nutrition and health.
Effects of Nonaxisymmetric Tip Clearance on Axial Compressor Performance and Stability
Authors: Graf M. B. , Wong T. S. , Greitzer E. M. , Marble F. E. , Tan C. S. , Shin H.-W. , Wisler D. C.
Published: December 2008

The effects of circumferentially nonuniform tip clearance on axial compressor performance and stability have been investigated experimentally and analytically. A theoretical model for compressor behavior with nonaxisymmetric tip clearance has been developed and used to design a series of first-of-a-kind experiments on a four-stage, low-speed compressor. The experiments and computational results together show clearly the central physical features and controlling parameters of compressor response to nonaxisymmetric tip clearance. It was found that the loss in stall margin was more severe than that estimated based on average clearance. The stall point was, in fact, closer to that obtained with uniform clearance at the maximum clearance level. The circumferential length scale of the tip clearance (and accompanying flow asymmetry) was an important factor in determining the stall margin reduction. For the same average clearance, the loss in peak pressure rise was 50 percent higher for an asymmetry with fundamental wavelength equal to the compressor circumference than with wavelength equal to one-half the circumference. The clearance asymmetry had much less of an effect on peak efficiency; the measured maximum efficiency decrease obtained was less than 0.4 percent compared to the 8 percent decrease in peak pressure rise due to the asymmetric clearance. The efficiency penalty due to nonaxisymmetric tip clearance was thus close to that obtained with a uniform clearance at the circumferentially averaged level. The theoretical model accurately captured the decreases in both steady-state pressure rise and stable operating range which are associated with clearance asymmetry. It also gave a good description of the observed trends of: (i) increasing velocity asymmetry with decreasing compressor flow, and (ii) decreasing effect of clearance asymmetry with decreasing dominant wavelength of the clearance distribution. The time-resolved data showed that the spatial structure of the prestall propagating disturbances in the compressor annulus was well represented and that the stability limiting process could be linked to the unsteady structure of these disturbance modes. The model was also utilized for parametric studies to define how compressor performance and stability are affected by the circumferential distribution of clearance, steady-state compressor pressure-rise characteristic, and system dynamic parameters. Sensitivity to clearance asymmetry was found to fall off strongly with the (asymmetry-related) reduced frequency and to increase with peak pressure rise and increasing curvature of the characteristic near the peak.
Sound Generation by a Centrifugal Pump at Blade Passing Frequency
Authors: Morgenroth M. , Weaver D. S.
Published: December 2008

This paper reports the results of an experimental study of the pressure pulsations produced by a centrifugal volute pump at its blade passing frequency and their amplification by acoustic resonance in a connected piping system. Detailed measurements were made of the pressure fluctuations in the piping as a function of pump speed and flow rate. A semi-empirical model was used to separate acoustic standing waves from hydraulic pressure fluctuations. The effects of modifying the cut-water geometry were also studied, including the use of flow visualization to observe the flow behavior at the cut-water. The results suggest that the pump may act as an acoustic pressure or velocity source, depending on the flow rate and the cut-water geometry. At conditions of acoustic resonance, the pump acted as an open termination of the piping, i.e., as a node in the acoustic pressure standing waves. Rounding the cut-water had the effect of reducing the amplitude of acoustic resonance, apparently because of the ability of the stagnation point to move and thereby reduce the vorticity generated.
Detailed Film Cooling Measurements on a Cylindrical Leading Edge Model: Effect of Free-Stream Turbulence and Coolant Density
Authors: Ekkad S. V. , Han J. C. , Du H.
Published: December 2008

Detailed heat transfer coefficient and film effectiveness distributions are presented on a cylindrical leading edge model using a transient liquid crystal technique. Tests were done in a low-speed wind tunnel on a cylindrical model in a crossflow with two rows of injection holes. Mainstream Reynolds number based on the cylinder diameter was 100,900. The two rows of injection holes were located at ±15 deg from stagnation. The film holes were spaced four hole diameters apart and were angled 30 and 90 deg to the surface in the spanwise and streamwise directions, respectively. Heat transfer coefficient and film effectiveness distributions are presented on only one side of the front half of the cylinder. The cylinder surface is coated with a thin layer of thermochromic liquid crystals and a transient test is run to obtain the heat transfer coefficients and film effectiveness. Air and CO2 were used as coolant to simulate coolant-to-mainstream density ratio effect. The effect of coolant blowing ratio was studied for blowing ratios of 0.4, 0.8, and 1.2. Results show that Nusselt numbers downstream of injection increase with an increase in blowing ratio for both coolants. Air provides highest effectiveness at blowing ratio of 0.4 and CO2 provides highest effectiveness at a blowing ratio of 0.8. Higher density coolant (CO2) provides lower Nusselt numbers at all blowing ratios compared to lower density coolant (air). An increase in free-stream turbulence has very small effect on Nusselt numbers for both coolants. However, an increase in free-stream turbulence reduces film effectiveness significantly at low blowing ratios for both coolants.
Low-Aspect-Ratio Rib Heat Transfer Coefficient Measurements in a Square Channel
Authors: Taslim M. E. , Korotky G. J.
Published: December 2008

Cooling channels, roughened with repeated ribs, are commonly employed as a means of cooling turbine blades. The increased level of mixing induced by these ribs enhances the convective heat transfer in the blade cooling cavities. Many previous investigations have focused on the heat transfer coefficient on the surfaces between these ribs and only a few studies report the heat transfer coefficient on the rib surfaces themselves. The present study investigated the heat transfer coefficient on the surfaces of round-corner, low-aspect-ratio (ARrib = 0.667) ribs. Twelve rib geometries, comprising three rib height-to-channel hydraulic diameters (blockage ratios) of 0.133, 0.167, and 0.25 as well as three rib spacings (pitch-to-height ratios) of 5, 8.5, and 10 were investigated for two distinct thermal boundary conditions of heated and unheated channel walls. A square channel, roughened with low-aspect-ratio ribs on two opposite walls in a staggered manner and perpendicular to the flow direction, was tested. An instrumented copper rib was positioned either in the middle of the rib arrangements or in the furthest upstream location. Both rib heat transfer coefficient and channel friction factor for these low-aspect-ratio ribs were also compared with those of square ribs, reported previously by the authors. Heat transfer coefficients of the furthest upstream rib and that of a typical rib located in the middle of the rib-roughened region of the passage wall were also compared.