bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation of systemic and local myeloid cell subpopulations by bone marrow cell–derived granulocyte–macrophage colony‐stimulating factor in experimental inflammatory arthritis
Authors: Cook Andrew D. , Turner Amanda L. , Braine Emma L. , Pobjoy Jarrad , Lenzo Jason C. , Hamilton John A.
Published: August 2011

Objective

Even though there are clinical trials assessing granulocyte–macrophage colony‐stimulating factor (GM‐CSF) blockade in rheumatoid arthritis (RA), questions remain as to how GM‐CSF acts as a proinflammatory cytokine. The aims of this study on the regulation of arthritis progression by GM‐CSF were to determine the source of the GM‐CSF, whether there are systemic effects, the changes in synovial tissue leukocyte populations, and the arthritis model dependence on GM‐CSF.

Methods

Bone marrow chimeras were used to determine the source of GM‐CSF required for the development of collagen‐induced arthritis (CIA). The K/BxN serum–transfer model of arthritis was tested in GM‐CSF−/− mice and using anti–GM‐CSF monoclonal antibodies. Cell populations from arthritic mice were assessed by differential staining and flow cytometry.

Results

In the CIA model, GM‐CSF produced by bone marrow–derived cells was required for arthritis development. GM‐CSF blockade, while ameliorating the development of CIA, was found to have systemic effects, limiting the increase in circulating Ly‐6Chigh monocytes and neutrophils. GM‐CSF blockade led to fewer synovial macrophages (both Ly‐6Chigh and Ly‐6Clow), neutrophils, and lymphocytes. In the absence of GM‐CSF, K/BxN serum–transfer arthritis initially developed normally; however, the numbers of Ly‐6Chigh monocytes and synovial macrophages (both Ly‐6Chigh and Ly‐6Clow) were again reduced, along with the peak disease severity and maintenance.

Conclusion

GM‐CSF is a key player in two arthritis models, participating in interactions between hemopoietic cells, both locally and systemically, to control myeloid cell numbers as well as presumably to “activate” them. These results could be useful for the analysis of current clinical trials targeting GM‐CSF in patients with RA.
RobustH∞observer‐based tracking control of stochastic immune systems under environmental disturbances and measurement noises
Authors: Chen Bor‐Sen , Lin Ying‐Po , Chuang Yung‐Jen
Published: August 2011

A robust H∞observer‐based tracking control of stochastic immune response is proposed for therapeutic enhancement to track a prescribed immune response under uncertain initial states, environmental disturbances and measurement noises. The statistics of initial condition, environmental and measurement noises are assumed unavailable. Further, the state variables may not all be available and may be corrupted by measurement noises. Therefore, an observer‐based control design is proposed for robust H∞observer‐based tracking control of stochastic immune systems. The robust H∞control is designed to track a prescribed immune model response in spite of environmental disturbances, uncertain initial conditions and measurement noises. Since the stochastic immune system is highly nonlinear, it is not easy to solve the robust H∞observer‐based tracking control problem directly. A fuzzy model is proposed to interpolate several linearized stochastic immune systems to approximate the nonlinear stochastic immune system via smooth fuzzy membership functions. By the fuzzy approximation method, the H ∞ observer‐based tracking control problem of stochastic immune systems could be easily solved via the linear matrix inequality (LMI) technique with the help of Robust Control Toolbox in Matlab. Finally, anin silicoexample is given to illustrate the design procedure and to confirm the efficiency of the proposed method.

Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Tragverhalten von Verbundankern in hoch‐ und ultrahochfestem Beton
Authors: Randl Norbert , Gusella Oliver
Published: August 2011

Anhand von rund 170 Dübelauszugsversuchen und weiteren begleitenden experimentellen Analysen wurde das Tragverhalten von Verbundankersystemen unterschiedlicher Hersteller in hochfesten und faserbewehrten ultrahochfesten Betonen untersucht. Variiert wurden neben den Betonuntergründen auch das Bohrverfahren, die Reinigungsintensität bei der Installation sowie die Bohrlochfeuchte.

Die Ergebnisse zeigen, dass abhängig vom jeweiligen Produkt die Verbundfestigkeit im hochfesten Beton tendenziell etwas geringer sein kann als im normalfesten Beton. Ausgehend vom bekannten Tragverhalten in normalfestem Beton, ist eine Extrapolation in den hochfesten Bereich nur bedingt möglich. Insbesondere Verbundankersysteme mit hoher Klebekraft erwiesen sich auch in hochfesten Untergründen als tauglich. Untersucht wurde in Versuchen mit weiter Abstützung auch die Versagensart Betonausbruch. In der Regel sind in hochfesten Untergründen je nach Klebekraft des Mörtels, Setztiefe und Betonfestigkeit, Bruch der Ankerstange, überwiegendes Verbundversagen oder Mischbrüche mit Verbundversagen im unteren und Betonausbruch im oberen Verankerungsbereich zu erwarten.

Behavior of adhesive anchors in high strength and ultra high performance concrete

Recently about 170 pull‐out tests and further experimental investigations with various chemical anchors installed in high strength and ultra high performance fiber reinforced concrete have been performed. Apart from the concrete base material, other parameters like drilling method, intensity of cleaning of the borehole and water saturation of the concrete have been varied. The results of the confined tests reveal that the bond strength of chemical anchor systems may decrease in high strength concrete. Based on the current state of the art in normal strength concrete, an extrapolation of the behavior to higher strength classes is hardly possible. Chemical anchors with low adhesive bonding might behave unsatisfactorily whereas high bond mortars usually will be suitable for application in high strength concretes. In addition unconfined pull‐out tests with large support widths have been performed. As a rule in high strength concrete, depending on the product, chemical anchors may fail in the majority of cases due to rupture of the steel rod, pull‐out or pull‐out combined with concrete cone breakout in the upper anchorage zone.
Enhanced chemiluminescence of the luminol–AgNO3 system by Ag nanoparticles
Authors: Li Shifeng , Sun Huimin , Wang Dong , Hong Jianguo , Tao Shanjun , Yu Haiyin , Wang Xiuhua , Wei Xianwen
Published: August 2011

The oxidation reaction of luminol with AgNO3 can produce chemiluminescence (CL) in the presence of silver nanoparticles (NPs) in alkaline solution. Based on the studies of UV‐vis absorption spectra, photoluminescence (PL) spectra and CL spectra, a CL enhancement mechanism is proposed. The CL emission spectrum of the luminol–AgNO3–Ag NPs system indicated that the luminophore was still 3‐aminophthalate. On injection of silver nanoparticles into the mixture of luminol and AgNO3, they catalysed the reduction of AgNO3 by luminol. The product luminol radicals reacted with the dissolved oxygen, to produce a strong CL emission. As a result, the CL intensity was substantially increased. Moreover, the influences of 18 amino acids, e.g. cystine, tyrosine and asparagine, and 25 organic compounds, including gallic acid, tannic acid and hydroquinone, on the luminol–AgNO3–Ag NPs CL system were studied by a flow‐injection procedure, which led to an effective method for detecting these compounds. Copyright © 2011 John Wiley & Sons, Ltd.
Monitoring folate status in population‐based surveys
Authors: Yetley Elizabeth A.
Published: August 2011

Folate status assessments depend primarily on the measurement of biomarkers such as serum and red blood cell folate. Lessons learned from a large national monitoring system such as the National Health and Nutrition Examination Survey and a public health intervention such as the implementation of folic acid fortification in the United States have provided useful insights into the challenges of assessing folate status and possible solutions for addressing these challenges. © 2011 International Union of Biochemistry and Molecular Biology, Inc. 2011
An in vitro model of glucose and lipid metabolism in a multicompartmental bioreactor
Authors: Vinci Bruna , Murphy Ellen , Iori Elisabetta , Meduri Francesco , Fattori Silvia , Marescotti Maria Cristina , Castagna Maura , Avogaro Angelo , Ahluwalia Arti
Published: August 2011

The energy balance in vivo is maintained through inter‐organ cross‐talk involving several different tissues. As a first step towards recapitulating the metabolic circuitry, hepatocytes, endothelial cells and adipose tissue were connected in a multicompartmental modular bioreactor to reproduce salient aspects of glucose and lipid metabolism in vitro. We first examined how the two‐way cellular interplay between adipose tissue and endothelial cells affects glucose and lipid metabolism. The hepatocyte cell line HepG2 was then added to the system, creating a three‐way connected culture, to determine whether circulating metabolite concentrations were normalized, or whether metabolic shifts, which may arise when endothelial cells and adipose tissue are placed in connection, were corrected. The addition of hepatocytes to the system prevented the drop in the concentrations of glucose, L‐alanine and lactate, and the rise in that of free fatty acids. There was no significant change in glycerol levels in either of the connected cultures. The results show that connected cultures recapitulate complex physiological systemic processes, such as glucose and lipid metabolism, and that the HepG2 hepatocytes normalize circulating metabolites in this in vitro environment in the presence of other cell types.
Recycling and adaptation of Klebsormidium flaccidum microalgae for the sustained production of gold nanoparticles
Authors: Dahoumane Si Amar , Djediat Chakib , Yéprémian Claude , Couté Alain , Fiévet Fernand , Coradin Thibaud , Brayner Roberta
Published: August 2011

Targeting the development of cell‐based bioreactors for the production of metal nanoparticles, the possibility to perform the sustained synthesis of colloidal gold using Klebsormidium flaccidum green algae was studied. A first strategy relying on successive growth/reduction/reseeding recycling steps demonstrated maintained biosynthesis capability of the microalgae but limitation in metal content due to toxic effects. An alternative approach consisting of progressive gold salt addition revealed to be suitable to favor cell adaptation to larger metal concentrations and supported particle release over month periods. Biotechnol. Bioeng. 2012;109: 284–288. © 2011 Wiley Periodicals, Inc.
A theoretical approach to zonation in a bioartificial liver
Authors: Davidson Adam J. , Ellis Marianne J. , Chaudhuri Julian B.
Published: August 2011

Bioartificial livers have yet to gain clinical acceptance. In a previous study, a theoretical model was utilized to create operating region charts that graphically illustrated viable bioartificial liver configurations. On this basis a rationale for the choice of operating and design parameters for the device was created. The concept is extended here to include aspects of liver zonation for further design optimization. In vivo, liver cells display heterogeneity with respect to metabolic activity according to their position in the liver lobule. It is thought that oxygen tension is a primary modulator of this heterogeneity and on this assumption a theoretical model to describe the metabolic zonation within an in vitro bioartificial liver device has been adopted. The distribution of the metabolic zones under varying design and operating parameters is examined. In addition, plasma flow rates are calculated that give rise to an equal distribution of the metabolic zones. The results show that when a clinically relevant number of cells are contained in the BAL (10 billion), it is possible to constrain each of the three metabolic zones to approximately one‐third of the cell volume. This is the case for a number of different bioreactor designs. These considerations allow bioartificial liver design to be optimized. Biotechnol. Bioeng. 2012;109: 234–243. © 2011 Wiley Periodicals, Inc.
Study and design of stability in GH5 cellulases
Authors: Badieyan Somayesadat , Bevan David R. , Zhang Chenming
Published: August 2011

Thermostable enzymes that hydrolyze lignocellulosic materials provide potential advantages in process configuration and enhancement of production efficiency over their mesophilic counterparts in the bioethanol industry. In this study, the dynamics of β‐1,4‐endoglucanases (EC: 3.2.1.4) from family 5 of glycoside hydrolases (GH5) were investigated computationally. The conformational flexibility of 12 GH5 cellulases, ranging from psychrophilic to hyperthermophilic, was investigated by molecular dynamics (MD) simulations at elevated temperatures. The results indicated that the protein flexibility and optimum activity temperatures are appreciably correlated. Intra‐protein interactions, packing density and solvent accessible area were further examined in crystal structures to investigate factors that are possibly involved in higher rigidity of thermostable cellulases. The MD simulations and the rules learned from analyses of stabilizing factors were used in design of mutations toward the thermostabilization of cellulase C, one of the GH5 endoglucanases. This enzyme was successfully stabilized both chemically and thermally by introduction of a new disulfide cross‐link to its highly mobile 56‐amino acid subdomain. Biotechnol. Bioeng. 2012;109: 31–44. © 2011 Wiley Periodicals, Inc.
Organoclay‐assisted interfacial polymerization for microfluidic production of monodisperse PEG‐microdroplets and in situ encapsulation of E. coli
Authors: Wang Kye Won , Lee Kyoung G. , Park Tae Jung , Lee Young‐Chul , Yang Ji‐Won , Kim Do Hyun , Lee Seok Jae , Park Jung Youn
Published: August 2011

We developed a novel one‐pot synthetic strategy for preparing monodisperse polyethylene glycol diacrylate (PEGDA) microdroplets via organoclay‐assisted interfacial polymerization approach for Escherichia coli encapsulation. Based on the mechanism of spontaneous and rapid polymerization of PEGDA precursor solution with Mg‐organoclay, the prepared PEGDA microdroplets have uniform size and fine round shape, with size range of 74–118 µm. The size of microdroplets can be controlled through the changing continuous phase flow rate. Organoclay‐assisted polymerization method provides a unique environment to produce non‐toxic ways of fabricating microorganism encapsulated microdroplets and to prohibit microdroplets merge during the processes. Furthermore, we successfully carried out to entrap E. coli inside of the PEGDA microdroplets. E. coli expressing a green fluorescent protein shows a good viability inside the PEGDA microdroplets. The in situ microfluidic synthetic method provides a novel approach for the preparation of monodisperse PEGDA microdroplets via a one‐pot route. Biotechnol. Bioeng. 2012;109: 289–294. © 2011 Wiley Periodicals, Inc.
Industrial glucoamylase fed‐batch benefits from oxygen limitation and high osmolarity
Authors: Pedersen Lasse , Hansen Kim , Nielsen Jens , Lantz Anna Eliasson , Thykaer Jette
Published: August 2011

The market for glucoamylase is large and very competitive and the production process has been optimized through several decades. So far a thorough characterization of the process has not been published, but previous academic reports suggest that the process suffers from severe byproduct formation. In this study we have carried out a thorough characterization of a process as close as possible to the industrial reality. The results show that the oxygen‐limited phases of the process have the highest glucoamylase yields on carbon and that the byproducts are efficiently reused in late phases of the process. An alternative process with low glucose concentration show that high osmolarity is beneficial for the process, and we conclude that oxygen limitation, high osmolarity, and the associated byproduct metabolism are important for the efficiency of the process. Biotechnol. Bioeng. 2012;109: 116–124. © 2011 Wiley Periodicals, Inc.
Synthesis and Antitumor Molecular Mechanism of Agents Based on Amino 2‐(3′,4′,5′‐Trimethoxybenzoyl)benzo[b]furan: Inhibition of Tubulin and Induction of Apoptosis
Authors: Romagnoli Romeo , Baraldi Pier Giovanni , Lopez‐Cara Carlota , Cruz‐Lopez Olga , Carrion Maria Dora , Kimatrai Salvador Maria , Bermejo Jaime , Estévez Sara , Estévez Francisco , Balzarini Jan , Brancale Andrea , Ricci Antonio , Chen Longchuan , Kim Jae Gwan , Hamel Ernest
Published: August 2011

Induction of apoptosis is a promising strategy that could lead to the discovery of new molecules active in cancer chemotherapy. This property is generally observed when cells are treated with agents that target microtubules, dynamic structures that play a crucial role in cell division. Small molecules such as benzo[b]furans are attractive as inhibitors of tubulin polymerization. A new class of inhibitors of tubulin polymerization based on the 2‐(3′,4′,5′‐trimethoxybenzoyl)benzo[b]furan molecular skeleton, with the amino group placed at different positions on the benzene ring, were synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell‐cycle effects. The methoxy substitution pattern on the benzene portion of the benzo[b]furan moiety played an important role in affecting antiproliferative activity. In the series of 5‐amino derivatives, the greatest inhibition of cell growth occurred if the methoxy substituent is placed at the C6 position, whereas C7 substitution decreases potency. The most promising compound in this series is 2‐(3′,4′,5′‐trimethoxybenzoyl)‐3‐methyl‐5‐amino‐6‐methoxybenzo[b]furan (3 h), which inhibits cancer cell growth at nanomolar concentrations (IC50=16–24 nM), and interacts strongly with tubulin by binding to the colchicine site. Sub‐G1 apoptotic cells in cultures of HL‐60 and U937 cells were observed by flow cytometric analysis after treatment with 3 h in a concentration‐dependent manner. We also show that compound 3 h induces apoptosis by activation of caspase‐3, ‐8, and ‐9, and this is associated with cytochrome c release from mitochondria. The introduction of an α‐bromoacryloyl group increased antiproliferative activity with respect to the parent amino derivatives.
Elimination of truncation and round off error and enhancement of stability using a new split loop DPLL
Authors: Sarkar Surjadeep , Chatterjee Basab , Maulik Ujjwal , Biswas Baidyanath
Published: August 2011

In contrast with the conventional split loop digital phase lock loop, a new loop is presented in this paper that differs from the earlier version principally by design aspects. It incorporates an additional phase modulation input along with its frequency modulation input in the digital controlled oscillator. It is capable of eliminating the deleterious effects of rounding and truncation error with faster signal accusation. Higher loop stability is also achievable using the new split loop digital phase lock loop. Furthermore, radio frequency filtering is done using an In phase and Quadrature phase (IQ) voltage controlled oscillator to avoid interaction between the loop filter and the radio frequency filter. Copyright © 2011 John Wiley & Sons, Ltd.
Bericht über die 70. Sitzung des Technischen Lenkungsausschusses der Europäischen Organisation für Technische Zulassungen
Authors: Springborn Matthias
Published: August 2011

Am 30. Mai/1. Juni 2011 fand die 70. Sitzung des Technischen Lenkungsausschusses der Europäischen Organisation für Technische Zulassungen (EOTA) in Berlin beim Deutschen Institut für Bautechnik statt.
IL‐10 limits production of pathogenic TNF by M1 myeloid cells through induction of nuclear NF‐κB p50 member in Trypanosoma congolense infection‐resistant C57BL/6 mice
Authors: Bosschaerts Tom , Morias Yannick , Stijlemans Benoît , Hérin Michel , Porta Chiara , Sica Antonio , Mantovani Alberto , De Baetselier Patrick , Beschin Alain
Published: August 2011

A balance between parasite elimination and control of infection‐associated pathogenicity is crucial for resistance to African trypanosomiasis. By producing TNF and NO, CD11b+ myeloid cells with a classical activation status (M1) contribute to parasitemia control in experimental Trypanosoma congolense infection in resistant C57BL/6 mice. However, in these mice, IL‐10 is required to regulate M1‐associated inflammation, avoiding tissue/liver damage and ensuring prolonged survival. In an effort to dissect the mechanisms behind the anti‐inflammatory activity of IL‐10 in T. congolense‐infected C57BL/6 mice, we show, using an antibody blocking the IL‐10 receptor, that IL‐10 impairs the accumulation and M1 activation of TNF/iNOS‐producing CD11b+Ly6C+ cells in the liver. Using infected IL‐10flox/floxLysM‐Cre+/+ mice, we show that myeloid cell‐derived IL‐10 limits M1 activation of CD11b+Ly6C+ cells specifically at the level of TNF production. Moreover, higher production of TNF in infected IL‐10flox/floxLysM‐Cre+/+ mice is associated with reduced nuclear accumulation of the NF‐κB p50 subunit in CD11b+ M1 cells. Furthermore, in infected p50−/− mice, TNF production by CD11b+Ly6C+ cells and liver injury increases. These data suggest that preferential nuclear accumulation of p50 represents an IL‐10‐dependent anti‐inflammatory mechanism in M1‐type CD11b+ myeloid cells that regulates the production of pathogenic TNF during T. congolense infection in resistant C57BL/6 mice.
VAMP4‐ and VAMP7‐expressing vesicles are both required for cytotoxic granule exocytosis in NK cells
Authors: Krzewski Konrad , Gil‐Krzewska Aleksandra , Watts James , Stern Joel N. H. , Strominger Jack L.
Published: August 2011

NK cells eliminate cancer and virus‐infected cells through their cytolytic activity. The last step in NK‐cell cytotoxicity, resulting in exocytosis of granule content, requires fusion of lytic granules with the plasma membrane. Proteins from the soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE) family mediate membrane fusion events in the cell. Here, we show that NK cells express all members of the R‐SNARE subgroup. Two of these R‐SNARE proteins, VAMP4 and VAMP7, colocalize with lytic granules during cytotoxic interactions. However, only VAMP7 associates with perforin‐containing granules in nonactivated cells, indicating that the two VAMPs have different functions in exocytosis. Using both the tumor NK‐cell line YTS and the peripheral NK cells, we show that the disruption of expression of either VAMP4 or VAMP7 inhibits the release of lytic granules and severely impairs NK‐cell cytotoxic activity. Furthermore, VAMP7 but not VAMP4 is involved in IFN‐γ secretion in NK cells, indicating that VAMP7 is involved in many fusion processes and thus plays a more general function in NK‐cell activity than VAMP4.
Release of TNF‐α from macrophages is mediated by small GTPase Rab37
Authors: Mori Ryoichi , Ikematsu Kazuya , Kitaguchi Tetsuya , Kim Sang E. , Okamoto Momoko , Chiba Takuya , Miyawaki Atsushi , Shimokawa Isao , Tsuboi Takashi
Published: August 2011

Activated macrophages at wound sites release many cytokines which positively affect skin wound healing. However, the molecular mechanisms controlling cytokine secretion from macrophages have not been elucidated. In the present study, we performed an RT‐PCR analysis and found that 19 small GTPase Rab isoforms were expressed at skin wound sites, with six of them (i.e. Rab3B, Rab27B, Rab30, Rab33A, Rab37, and Rab40C) being upregulated during the inflammation and proliferation/migration phase of skin repair. We also found that gene expression of Rab37 in murine primary and RAW264.7 macrophages was significantly induced after stimulation with LPS. Overexpression of wild type and constitutively active Rab37 in RAW264.7 cells significantly increased TNF‐α secretion, whereas knockdown of Rab37 by siRNA significantly decreased it. We also identified 29 putative Rab37‐interacting proteins, including the membrane fusion regulating Munc13‐1, using liquid chromatography/linear ion trap mass spectrometry (LC‐MS/MS). Immunocytochemical analysis further revealed that TNF‐α‐containing vesicles were colocalized with both Rab37 and Munc13‐1 in activated macrophages. Knockdown of Munc13‐1 by siRNA significantly decreased TNF‐α secretion. Taken together, these findings demonstrate that Rab37 interacts with Munc13‐1 to control TNF‐α secretion from activated macrophages.
A Convenient Synthesis of Cyclopentadienylgallium – The Awakening of a Sleeping Beauty in Organometallic Chemistry
Authors: Schenk Christian , Köppe Ralf , Schnöckel Hansgeorg , Schnepf Andreas
Published: August 2011

Solid “GaI” reacts with NaCp to yield (η5‐cyclopentadienyl)gallium (GaCp) (1). During the synthesis the side product, CpGa→GaCp2I (2), with a rare gallium–gallium donor–acceptor bond could be isolated. The reaction of 1 with B(C6F5)3 affords CpGa→B(C6F5)3 (4). The molecular structures of 2 and 4, which contain the first GaCp moieties, are presented. The convenient synthesis of 1 needs only standard laboratory equipment and certainly opens the door for 1 to become a versatile reagent in organometallic chemistry; awakening the sleeping beauty GaCp nearly twenty years after its initial discovery.
The conclusions of risk analysis as a basis for deciding between variants through the example of Contract H8 / Ein Fazit zur Risikoanalyse als Grundlage für eine Variantenentscheidung am Beispiel Los H8
Authors: Spiegl Markus , Sander Philip , Pellar Alfred , Maidl Ulrich , Herdina Johann , Feistmantl Klaus
Published: August 2011

The Brenner Eisenbahn GmbH (BEG) was appointed in 1995 to design and construct the new railway line in the Lower Inn Valley between the national border near Kufstein and Innsbruck. In the densely populated Inn Valley, large parts of the line with a planned speed of 250 km/h had to be run through tunnels. Near Jenbach, a semi‐quantitative process was used as part of a risk analysis for the decision between the variants of a shallow, mined special construction and a deep mechanically driven tunnel.

Die Brenner Eisenbahn GmbH (BEG) wurde im Jahr 1995 mit der Planung und Errichtung der Neubaustrecke im Unterinntal zwischen der Staatsgrenze bei Kufstein und Innsbruck beauftragt. Im dicht bebauten Inntal mussten große Teile der mit einer Spitzengeschwindigkeit von 250 km/h geplanten Strecke in Tunnellage errichtet werden. Im Bereich Jenbach wurde ein semi‐quantitatives Verfahren im Rahmen der Risikoanalyse zur Variantenentscheidung zwischen einer seicht liegenden, bergmännischen Sonderbauweise und einem tiefliegende Maschinenvortrieb angewandt.
Criteria for the selection of tunnelling method through the example of the Koralm Tunnel / Kriterien zur Wahl der Vortriebsarten am Beispiel des Koralmtunnels
Authors: Moritz Bernd , Wagner Hanns , Mussger Klaus , Handke Dieter , Harer Gerhard
Published: August 2011

With a length of 32.9 km, the Koralm tunnel is the key structure on the route of the new 130 km Koralm railway between Graz and Klagenfurt (Austria). This paper defines the most important boundary conditions for dividing the sections and for selecting the methods of tunnelling (sequential or continuous). The focus of the article is mainly on section KAT 3, in which both tertiary sediments and crystalline rock sequences, including the Lavanttal fault zone, are excavated by sequential and continuous tunnelling. The considerations for this section also include the decision to excavate the sediments and the Lavanttal fault zone using a shield machine with earth pressure components. The criteria for defining the different operating modes are described.

Der Koralmtunnel mit einer Länge von 32,9 km stellt das Schlüsselbauwerk entlang der 130 km langen neuen Koralmbahn zwischen Graz und Klagenfurt dar. Der vorliegende Beitrag legt die wesentlichen Randbedingungen zur Einteilung der Baulose und zur Wahl der jeweiligen Vortriebsmethode (zyklisch oder kontinuierlich) dar. Der Fokus ist dabei hauptsächlich auf das Baulos KAT 3 gerichtet, in dem sowohl tertiäre Sedimente als auch kristalline Gesteinsabfolgen mitsamt der Lavanttaler Störungszone im zyklischen und im kontinuierlichen Vortrieb durchörtert werden. Die Betrachtungen für dieses Baulos umfassen auch die Entscheidungsfindung, die Sedimente und die Lavanttaler Störungszone mittels Schildmaschine mit Erddruckkomponenten aufzufahren. Die Kriterien zur Abgrenzung der unterschiedlichen Betriebsmodi werden dargestellt.
TBM versus NATM from the contractor's point of view / TBM versus NÖT aus Sicht des Unternehmers
Authors: Gütter Wolfgang , Jäger Manfred , Rudigier Günther , Weber Wolfgang
Published: August 2011

The selection of the correct method of tunnelling from the contractor's point of view mostly depends on its chance to survive the competition of the marketplace, in addition to a host of technical constraints. The tendering and award conditions also decisively influence whether the technically and economically optimal solution is chosen.

There are also other factors like the market situation, availability of suitable tunnelling machinery and personnel resources, which can have a significant effect on the decision process.

Die Wahl der aus Sicht des Unternehmers richtigen Vortriebsmethode hängt neben einer Vielzahl technischer Randbedingungen vor allem davon ab, wie dieser damit im Wettbewerb bestehen kann. Dabei beeinflussen die Ausschreibungs‐ und Vergabebedingungen ganz wesentlich, ob letztlich auch die technisch und wirtschaftlich optimale Lösung zur Ausführung gelangt. Daneben sind es aber auch Faktoren wie Marktsituation, Verfügbarkeit von geeigneten Vortriebsanlagen, Personalressourcen, die im Entscheidungsprozess der Vortriebsmethode eine gravierende Rolle spielen können.
A protective antiarrhythmic role of ursodeoxycholic acid in an in vitro rat model of the cholestatic fetal heart
Authors: Miragoli Michele , Kadir Siti H. Sheikh Abdul , Sheppard Mary N. , Salvarani Nicoló , Virta Matilda , Wells Sarah , Lab Max J. , Nikolaev Viacheslav O. , Moshkov Alexey , Hague William M. , Rohr Stephan , Williamson Catherine , Gorelik Julia
Published: August 2011

Intrahepatic cholestasis of pregnancy may be complicated by fetal arrhythmia, fetal hypoxia, preterm labor, and, in severe cases, intrauterine death. The precise etiology of fetal death is not known. However, taurocholate has been demonstrated to cause arrhythmia and abnormal calcium dynamics in cardiomyocytes. To identify the underlying reason for increased susceptibility of fetal cardiomyocytes to arrhythmia, we studied myofibroblasts (MFBs), which appear during structural remodeling of the adult diseased heart.

In vitro

, they depolarize rat cardiomyocytes via heterocellular gap junctional coupling. Recently, it has been hypothesized that ventricular MFBs might appear in the developing human heart, triggered by physiological fetal hypoxia. However, their presence in the fetal heart (FH) and their proarrhythmogenic effects have not been systematically characterized. Immunohistochemistry demonstrated that ventricular MFBs transiently appear in the human FH during gestation. We established two

in vitro

models of the maternal heart (MH) and FH, both exposed to increasing doses of taurocholate. The MH model consisted of confluent strands of rat cardiomyocytes, whereas for the FH model, we added cardiac MFBs on top of cardiomyocytes. Taurocholate in the FH model, but not in the MH model, slowed conduction velocity from 19 to 9 cm/s, induced early after depolarizations, and resulted in sustained re-entrant arrhythmias. These arrhythmic events were prevented by ursodeoxycholic acid, which hyperpolarized MFB membrane potential by modulating potassium conductance.

Conclusion:

These results illustrate that the appearance of MFBs in the FH may contribute to arrhythmias. The above-described mechanism represents a new therapeutic approach for cardiac arrhythmias at the level of MFB. (Hepatology 2011;)
Multipotent stem/progenitor cells in human biliary tree give rise to hepatocytes, cholangiocytes, and pancreatic islets
Authors: Cardinale Vincenzo , Wang Yunfang , Carpino Guido , Cui Cai-Bin , Gatto Manuela , Rossi Massimo , Berloco Pasquale Bartolomeo , Cantafora Alfredo , Wauthier Eliane , Furth Mark E. , Inverardi Luca , Dominguez-Bendala Juan , Ricordi Camillo , Gerber David , Gaudio Eugenio , Alvaro Domenico , Reid Lola
Published: August 2011

Multipotent stem/progenitors are present in peribiliary glands of extrahepatic biliary trees from humans of all ages and in high numbers in hepato-pancreatic common duct, cystic duct, and hilum. They express endodermal transcription factors (e.g., Sox9, SOX17, FOXA2, PDX1, HES1, NGN3, PROX1) intranuclearly, stem/progenitor surface markers (EpCAM, NCAM, CD133, CXCR4), and sometimes weakly adult liver, bile duct, and pancreatic genes (albumin, cystic fibrosis transmembrane conductance regulator [CFTR], and insulin). They clonogenically expand on plastic and in serum-free medium, tailored for endodermal progenitors, remaining phenotypically stable as undifferentiated cells for months with a cell division initially every ≈36 hours and slowing to one every 2-3 days. Transfer into distinct culture conditions, each comprised of a specific mix of hormones and matrix components, yields either cords of hepatocytes (express albumin, CYP3A4, and transferrin), branching ducts of cholangiocytes (expressing anion exchanger-2-AE2 and CFTR), or regulatable C-peptide secreting neoislet-like clusters (expressing glucagon, insulin) and accompanied by changes in gene expression correlating with the adult fate. Transplantation into quiescent livers of immunocompromised mice results in functional human hepatocytes and cholangiocytes, whereas if into fat pads of streptozocin-induced diabetic mice, results in functional islets secreting glucose-regulatable human C-peptide.

Conclusion:

The phenotypes and availability from all age donors suggest that these stem/progenitors have considerable potential for regenerative therapies of liver, bile duct, and pancreatic diseases including diabetes. (Hepatology2011;)
HAb18G/CD147 promotes cell motility by regulating annexin II-activated RhoA and Rac1 signaling pathways in hepatocellular carcinoma cells
Authors: Zhao Pu , Zhang Wei , Wang Shi-Jie , Yu Xiao-Ling , Tang Juan , Huang Wan , Li Yong , Cui Hong-Yong , Guo Yun-Shan , Tavernier Jan , Zhang Si-He , Jiang Jian-Li , Chen Zhi-Nan
Published: August 2011

Tumor cells can move as individual cells in two interconvertible modes: mesenchymal mode and amoeboid mode. Cytoskeleton rearrangement plays an important role in the interconversion. Previously, we reported that HAb18G/CD147 and annexin II are interacting proteins involved in cytoskeleton rearrangement, yet the role of their interaction is unclear. In this study we found that the depletion of HAb18G/CD147 produced a rounded morphology, which is associated with amoeboid movement, whereas the depletion of annexin II resulted in an elongated morphology, which is associated with mesenchymal movement. The extracellular portion of HAb18G/CD147 can interact with a phosphorylation-inactive mutant of annexin II and inhibit its phosphorylation. HAb18G/CD147 inhibits Rho signaling pathways and amoeboid movement by inhibiting annexin II phosphorylation, promotes membrane localization of WAVE2 and Rac1 activation by way of the integrin-FAK-PI3K/PIP3 signaling pathway, and promotes the formation of lamellipodia and mesenchymal movement.

Conclusion:

These results suggest that the interaction of HAb18G/CD147 with annexin II is involved in the interconversion between mesenchymal and amoeboid movement of hepatocellular carcinoma cells. (Hepatology 2011)
Differential contribution of SLC26A9 to Cl− conductance in polarized and non‐polarized epithelial cells
Authors: Ousingsawat Jiraporn , Schreiber Rainer , Kunzelmann Karl
Published: August 2011

SLC26 proteins function as anion exchangers and Cl− channels. SLC26A9 has been proposed to be a constitutively active and CFTR‐regulated anion conductance in human bronchial epithelia. This positive interaction between two Cl− channels has been questioned by others and evidence has been provided that CFTR rather inhibits the transport activity of SLC26A9. We therefore examined the functional interaction between CFTR and SLC26A9 in polarized airway epithelial cells and in non‐polarized HEK293 cells expressing CFTR and SLC26A9. We found that SLC26A9 provides a constitutively active basal Cl− conductance in polarized grown CFTR‐expressing CFBE airway epithelial cells, but not in cells expressing F508del‐CFTR. In polarized CFTR‐expressing cells, SLC26A9 also contributes to both Ca2+‐ and CFTR‐activated Cl− secretion. In contrast in non‐polarized HEK293 cells co‐expressing CFTR/SLC26A9, the baseline Cl− conductance provided by SLC26A9 was inhibited during activation of CFTR. SLC26A9 and CFTR behave differentially in polarized and non‐polarized cells, which may explain earlier conflicting data. J. Cell. Physiol. 227: 2323–2329, 2012. © 2011 Wiley Periodicals, Inc.
Eph‐2B, acting as an extracellular ligand, induces differentiation markers in epidermal keratinocytes
Authors: Walsh Rebecca , Blumenberg Miroslav
Published: August 2011

In the bi‐directional signaling system comprising ephrins (EFNs) and ephrin receptors (Ephs), both EFNs and Ephs simultaneously function both as ligands and as receptors. Importantly, the EFN/Eph system is deregulated in human cancers and has been implicated in the metastatic processes because of its effects on the adhesion and migration of epithelial cells. The idiosyncratic function of Ephs, membrane‐bound receptor kinases, as extracellular signaling ligands, has not been extensively studied. This prompted us to explore the transcriptional targets regulated by Ephs acting solely as ligands. To define the ligand function of EphB2 in human epidermal keratinocytes, we treated these cells with EphB2 as Fc‐conjugate dimmers, which thus act exclusively as extracellular ligands. We compared the EphB2 and EFNA4 effects during a 48 h time course, using transcriptional profiling. We found that EphB2, acting as a ligand, promotes epidermal differentiation. For example, EphB2 induces expression of markers of epidermal differentiation, including keratins KRT1 and KRT10, SPRRs, desmosomal proteins and cell cycle inhibitors, while suppressing basal layer markers, integrins and cell cycle proteins. The effects of EphB2 are delayed relative to those of EFNA4. Unlike EFNA4, EphB2 did not induce lipid metabolism proteins, this particular aspect of epidermal differentiation seems not to be regulated by EphB2. Our results define the transcriptional targets of the reverse signaling by EphB2 acting exclusively as a ligand and begin to characterize this intriguing function of Ephs. J. Cell. Physiol. 227: 2330–2340, 2012. © 2011 Wiley Periodicals, Inc.
Nearest neighbor analysis of dopamine D1 receptors and Na+‐K+‐ATPases in dendritic spines dissected by STED microscopy
Authors: Blom Hans , RöNnlund Daniel , Scott Lena , Spicarova Zuzana , Rantanen Ville , Widengren Jerker , Aperia Anita , Brismar Hjalmar
Published: August 2011

Protein localization in dendritic spines is the focus of intense investigations within neuroscience. Applications of super‐resolution microscopy to dissect nanoscale protein distributions, as shown in this work with dual‐color STED, generate spatial correlation coefficients having quite small values. This means that colocalization analysis to some extent looses part of its correlative impact. In this study we thus introduced nearest neighbor analysis to quantify the spatial relations between two important proteins in neurons, the dopamine D1 receptor and Na+,K+‐ATPase. The analysis gave new information on how dense the D1 receptor and Na+,K+‐ATPase constituting nanoclusters are located both with respect to the homogenous (self to same) and the heterogeneous (same to other) topology. The STED dissected nanoscale topologies provide evidence for both a joint as well as a separated confinement of the D1 receptor and the Na+,K+‐ATPase in the postsynaptic areas of dendritic spines. This confined topology may have implications for generation of local sodium gradients and for structural and functional interactions modulating slow synaptic transmission processes. Microsc. Res. Tech., 2011. © 2011 Wiley Periodicals, Inc
Cytotoxic effects of permethrin on mouse liver and spleen cells
Authors: Roma Gislaine Cristina , Oliveira Patrícia Rosa De , Bechara Gervásio Henrique , Mathias Maria Izabel Camargo
Published: August 2011

This study analyzed the histopathological and histochemical effects of different dosages of permethrin on liver and spleen cells of mice, in order to evaluate the toxic potential of this substance and the possible impairments that this chemical causes in different tissues of nontarget organisms (laboratorial conditions). The results showed that permethrin caused severe alterations in the liver cells, reducing the size of the nuclei and causing hydropic degeneration of the hepatocytes, in addition to stimulating the proliferation of Kupffer cells, altered the amount of proteins, polysaccharides, lipids, and vacuoles in the cytoplasm of the hepatocytes and congested the hepatic capillaries. As for the spleen of the treated mice, no alterations were observed in the morphology in relation to the control group, what would suggest that the spleen would continue performing its functions, without suffering morphological alterations even in the presence of the toxic agent. © Microsc. Res. Tech., 2011. © 2011 Wiley Periodicals, Inc.
Fluorescence recognition of proteinaceous binders in works of art by a novel integrated system of investigation
Authors: Sandu Irina Crina Anca , Roque Ana Cecilia A. , Matteini Paolo , Schäfer Stephan , Agati Giovanni , Correia Catarina Ribeiro , Viana Joana Fortio Fernandes Pacheco
Published: August 2011

Fluorescence microscopy and microspectrofluorometry are important tools in the characterization and identification of proteins, offering a great range of applications in conservation science. Because of their high selectivity and sensitivity, the combination of these techniques can be exploited for improved recognition and quantification of proteinaceous binders in paintings and polychromed works of art. The present article explores an analytical protocol integrating fluorescence microscopy and fluorometry for both identification and mapping of proteinaceous binders (in particular egg and glues) in paint samples. The study has been carried out on historically accurate reconstructions simulating the structure and composition of tempera and oil paints containing these binders. To assess the spatial distribution of specific proteins within the paint layers, cross‐sections from the reconstructions were analyzed by fluorescence imaging after staining with an exogenous fluorophore. Reference fluorescence spectra for each layer were acquired by a multichannel spectral analyzer and compared after Gaussian deconvolution. The results obtained demonstrated the effectiveness of the integrated protocol, highlighting the potential for the use of fluorescent staining coupled with microspectrofluorometry as a routine diagnostic tool in conservation science. The current work creates a set of fully characterized reference samples for further comparison with those from actual works of art. Microsc. Res. Tech., 2011. © 2011 Wiley Periodicals, Inc.
Running in cold weather: morphology, thermal biology, and performance in the southernmost lizard clade in the world (Liolaemus lineomaculatussection: Liolaemini: Iguania)
Authors: Bonino Marcelo Fabián , Azócar Débora Lina Moreno , Tulli María José , Abdala Cristian Simón , Perotti María Gabriela , Cruz Félix Benjamín
Published: August 2011

The integration or coadaptation of morphological, physiological, and behavioral traits is represented by whole‐organism performance traits such as locomotion or bite force. Additionally, maximum sprint speed is a good indicator of whole‐organism performance capacity as variation in sprinting ability can affect survival. We studied thermal biology, morphology, and locomotor performance in a clade ofLiolaemuslizards that occurs in the Patagonian steppe and plateaus, a type of habitat characterized by its harsh cold climate.Liolaemusof thelineomaculatussection display a complex mixture of conservative and flexible traits. The phylogenetically informed analyses of these tenLiolaemusspecies show little coevolution of their thermal traits (only preferred and optimum temperatures were correlated). With regard to performance, maximum speed was positively correlated with optimum temperature. Body size and morphology influenced locomotor performance. Hindlimbs are key for maximal speed, but forelimb length was a better predictor for sustained speed (i.e. average speed over a total distance of 1.2 m). Finally, sustained speed differed among species with different diets, with herbivores running on average faster over a long distance than omnivores.J. Exp. Zool. 315:495–503, 2011. © 2011 Wiley‐Liss, Inc.
Evaluation of the DEMETER performance for seasonal hindcasts of the Indian summer monsoon rainfall
Authors: Ma Shujie , Rodó Xavier , Doblas‐Reyes Francisco J.
Published: August 2011

On the basis of the observed all‐India rainfall (AIR), Climate Prediction Center (CPC) merged analysis of precipitation (CMAP), and the multimodel rainfall simulated in the Development of a European multimodel ensemble system for seasonal to interannual prediction (DEMETER) project, the model performance in terms of forecast quality of the seasonal mean Indian summer monsoon rainfall (ISMR) was evaluated. The approach used included the individual model (single‐model ensemble) comparison as well as its comparison with the multimodel ensemble (MME). The results obtained reveal that systematic biases are the main source of the low skill in predicting the ISMR, while improved reproduction of interannual variability may increase the overall forecast quality for the ISMR. The MME shows superior performance in reproducing AIR features than the single‐model ensembles. This improved forecast quality achieved by the MME with respect to the ISMR variations primarily depends on model performance and secondly on ensemble size. The MME has improved capability of simulating the ISMR variations during 1972–1990 decades, whereas it exhibits a lower performance in the 1990s. The reason of this decadal varying forecast quality clearly deserves more investigation. In summary, these results suggest that the MME's increase in skill absolutely depends on enhancing the individual model quality. Copyright © 2011 Royal Meteorological Society
Lower limb kinematic alterations during drop vertical jumps in female athletes who have undergone anterior cruciate ligament reconstruction
Authors: Delahunt Eamonn , Sweeney Lauren , Chawke Mark , Kelleher Judy , Murphy Katie , Patterson Matt , Prendiville Anna
Published: August 2011

The aim of this study was to determine if anterior cruciate ligament reconstructed (ACL‐R) female athletes exhibit altered lower limb kinematic profiles during jump landing when compared to a non‐injured age, sex, and activity matched control group. Fourteen ACL‐R and 14 non‐injured control subjects performed 3 vertical drop jump (DVJ) trials. Lower limb kinematics were recorded at 200 Hz. Peak and time‐averaged angular displacements were quantified and utilized for between‐group analysis. The ACL‐R group displayed altered hip joint frontal and transverse plane kinematic alterations, and knee joint frontal and sagittal plane kinematic alterations. Specifically the ACL‐R group displayed an increased adducted (p < 0.05) and internally rotated (p < 0.05) hip joint position, both peak and time‐averaged, following landing. The ACL‐R group also displayed a decreased adducted (p < 0.05) and flexed (p < 0.05) position of the knee joint following landing. The observed aberrant lower limb kinematics could pre‐dispose ACL‐R athletes to potential future knee joint injuries. Further studies are required to determine in a prospective manner whether such deficits increase the incidence of recurrent ACL injury, and whether specific sensorimotor protocols following ACL reconstruction can minimize these kinematic deficits. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:72–78, 2012