bluuebunny/crossref_metadata_2025 huggingface dataset:
Leistungsfähigkeit von geodätischen Monitoringsystemen
Authors: Stempfhuber Werner
Published: November 2012

Geodätische Monitoringsysteme weisen heutzutage einen sehr hohen Automatisierungsgrad auf. Kommerzielle Gesamtlösungen können effizient auf die individuellen Anforderungen der Objektüberwachungen angepasst werden. Durch die präzise Definition der Überwachungsparameter, die Beobachtung von bekannten Messpunkten am Messobjekt und die Beschreibung des dynamischen Auswertemodells kann ein technisches Bauwerk oder eine Geländeoberfläche analysiert werden. Zur Bestimmung der geometrischen Veränderungen am Überwachungsobjekt stehen viele geodätische und geotechnische Messsensoren zur Verfügung.

Dieser Artikel behandelt die Leistungsfähigkeit der Monitoringsysteme mit geodätischen Messinstrumenten. In den meisten Anwendungsfällen des geodätischen Monitoring werden High‐end‐Instrumente eingesetzt. Die genaue Datenanalyse wie z.B. Deformationen, Rissbildungen oder Schwingungen muss dabei individuell durchgeführt werden. Eine weitere Herausforderung ist die automatisierte Verarbeitung der enormen Beobachtungsdaten. Die Visualisierung des Überwachungszustandes und entsprechender Alarmierung über ein Netzwerk dient zur stetigen Qualitätskontrolle. Zusätzlich muss die Zuverlässigkeit des Gesamtsystems gewährleistet werden. Für eine weitere Verbreitung und einen verstärkten Einsatz im Bauwesen, Maschinenbau oder bei verschiedenen Geowissenschaften müssen diese komplexen Systeme verstärkt an die Anwenderbedürfnisse angepasst werden. Zusätzlich ist eine verstärkte Einbindung von Low‐cost‐Messsystemen erforderlich.

Performance of Geodatic Monitoring Systems

Geodetic monitoring systems in these present days exhibit an extremely high level of automation. Commercial total solutions can be efficiently customised toward the individual demands of the object monitoring. A technical structure or a ground level surface can be analysed through the precise definition of the monitoring parameters, the observation of designated measuring points within the object measured and the description of the dynamic evaluation model. A variety of geodetic and geotechnical measuring sensors are available for the determination of geometrical changes within the object monitored. This article addresses the efficiency and performance of the monitoring systems with geodetic measuring instruments. High‐end instruments are utilised in most applications of geodetic monitoring. In the process, the exact data analysis, as for example with deformations, crackings or oscillations, must be conducted individually. Another challenge is the automated processing of the enormous amount of observation data. The visualisation of the monitoring status and a suitable alarm through the network serves for a continual quality control. In addition, the reliability of the entire system must be ensured. For further distribution and reinforced application within the construction industry, mechanical engineering or within the various geosciences, these complex systems must increasingly be adapted to user needs. In addition, a reinforced integration of low cost‐measuring systems is necessary.
Dünnwandiges Schalentragwerk aus textilbewehrtem Beton
Authors: Scholzen Alexander , Chudoba Rostislav , Hegger Josef
Published: November 2012

An der RWTH Aachen entsteht aktuell ein Pavillon mit einer Dachkonstruktion aus textilbewehrtem Beton, einem Verbundwerkstoff aus hochfestem Feinbeton und einer nichtrostenden textilen Bewehrung. Das filigrane Schalentragwerk demonstriert eindrucksvoll die Leistungsfähigkeit des innovativen Baustoffes.

Der Beitrag erläutert den Bemessungsansatz für flächig bewehrte Textilbetonbauteile und beschreibt die numerische Auswertung auf Basis von Finite‐Elemente‐Berechnungen des Tragwerks. Darüber hinaus werden baupraktische Aspekte der Realisierung, insbesondere die Herstellung der Textilbetonschalen im Spritzbetonverfahren, das entwickelte Bewehrungskonzept und die Montage der Schalen auf den Fertigteilstützen erläutert.

Thin‐walled shell structure made of textile reinforced concrete: design, dimensioning and realization

At RWTH Aachen University currently a pavilion is being realized with a roof construction made of textile reinforced concrete (TRC), a composite material consisting of a high‐strength, fine grained concrete and a noncorroding textile reinforcement. The thin‐walled TRC‐shell structure demonstrates impressively the load‐bearing capacity of this innovative composite material. The present contribution discusses the dimensioning approach for TRC‐shell structures and the numerical evaluation based on finite‐element analysis of the structure. Furthermore practical issues concerning the realization of the construction are discussed, such as the fabrication of the TRC shells using shotcrete, the developed concepts for the arrangement of the textile reinforcement, as well as the mounting of the shells on top of the precast concrete columns.
Dauerhaftigkeit von Stahlbeton in Tunnelbauwerken – Einfluss von Baumängeln
Authors: Gehlen Christoph , Kapteina Gesa
Published: November 2012

Der vorliegende Beitrag befasst sich mit dem Einfluss von Baumängeln auf die Dauerhaftigkeit von Stahlbetonbauteilen im Tunnelbau. Da Anforderungen an die Dauerhaftigkeit i. A. durch deskriptive Vorgaben definiert werden, ist die objektive Bewertung von Baumängeln und die Dimensionierung von geeigneten Maßnahmen zur Mängelbehebung kaum möglich. Werden hingegen leistungsbezogene Dauerhaftigkeitsanforderungen definiert, so steht ein neuer Lösungsweg zur Verfügung, welcher eine objektivere Bewertung der Baumängel ermöglicht. Auf dieser Grundlage können geeignete Maßnahmen zur Mängelbehebung gewählt und dimensioniert werden. Die dabei vorgestellte Vorgehensweise kann im Prinzip auch für die objektivere Beurteilung der Leistungsfähigkeit von instand gesetzten Bauteilen angewendet werden.

Durability of Reinforced Concrete in Tunnels: Influence of Building Defects

The present paper outlines the influence of deficiencies linked to reinforced concrete constructions on the durability. As requirements related to durability matters are in general defined by descriptive guidelines, the objective assessment of deficiencies and the dimensioning of necessary measures for retrofitting are hardly feasible. Whereas a definition of the durability of performance related requirements enables a new procedure to assess deficiencies more objectively. On this basis feasible measures can be chosen and dimensioned. In principle this introduced procedure can also be applied for the performance related assessment of the retrofitted structure.
“Söderströmstunneln” – Technische Herausforderungen bei Planung und Bau des Söderströmstunnels, Stockholm
Authors: Pöllath Klaus , Glückert Johannes
Published: November 2012

Im Zentrum von Stockholm wird derzeit der Eisenbahntunnel “Söderströmstunneln” gebaut. Der Absenktunnel unterquert den Söderström, einen Seitenarm des Sees Mälaren, und bildet das Verbindungsstück zwischen zwei Felstunneln. Er besteht aus zwei Anschlussbauwerken und drei einzelnen Tunnelelementen, die in schwimmenden Stahlschalungen betoniert, auf Pfahlgründungen abgesenkt und anschließend auf dem Seeboden monolithisch miteinander verbunden und vorgespannt werden.

“Söderströmstunneln” – technical challenge of planing and building the Söderström tunnel in Stockholm

The railway tunnel “Söderströmstunneln” is currently under construction in the heart of Stockholm. The immersed tunnel is crossing the Söderström, a branch of the lake Mälaren, and is forming the connecting part between two rock tunnels. He consists out of two connection structures and three single tunnel elements that are cast in floating steel shells. The tunnel elements will then be immersed on pile foundations and on the lake bottom monolithically connected and post‐tensioned.
Auswirkungen der geometrischen Lage der Tunnel auf die Gebirgsplastifizierung und die Spritzbetonschale beim Brenner Basistunnel
Authors: Bergmeister Konrad , Weifner Tassilo , Collizzollo Mara
Published: November 2012

Der Brenner Basistunnel wird mit einer Gesamtlänge von 64 km die weltlängste unterirdische Eisenbahnverbindung. Etwa 11 m unterhalb der beiden Tunnelröhren wird vorauseilend abschnittsweise ein Erkundungsstollen gebaut, um das Gebirge zu erforschen. Die geometrische Lage des Erkundungsstollens variiert in Bezug auf die beiden Haupttunnel im Nahebereich von Innsbruck und Franzensfeste. Diese horizontale Verschiebung und damit eine mögliche Gebirgsplastifizierung ist Gegenstand der Untersuchung. Ziel dieser Untersuchungen war es, die Auswirkungen der veränderten Einwirkungen aufgrund unterschiedlicher geometrischer Lagen der Tunnel auf die Dicke der Spritzbetonschale zu erforschen. Dabei wurden umfangreiche FE‐Simulationen durchgeführt und erstmalig in einer großen Serie In‐situ die mechanischen und geometrischen Kennwerte der Spritzbetonaußenschale ermittelt. Durch eine statistische Auswertung konnte auf Grundlage einer probabilistischen Betrachtung die notwendige Dicke der Spritzbetonschale verifiziert werden. Dabei wurde erkundet, ob die Spritzbetondicke des Erkundungsstollens auch für eine außermittige Lage (bis unterhalb der Haupttunnel) bzw. bei einem zusätzlichen mittig verlaufenden Stollen ausreicht.

Effects of the geometric position of the Brenner Base Tunnel on rock mass plastification and the tunnel's shotcrete shell

The Brenner Base Tunnel will be, at 64 kilometres, the longest underground railway connection in the world. A preliminary exploratory tunnel is being excavated in segments about 11 metres under the two main tunnels in order to prospect the rock mass. The geometric position of the exploratory tunnel varies, with respect to the main tunnels, near Innsbruck and Fortezza. This horizontal displacement and the possible plastification of the rock mass are the focus of this study. The aim of the analyses was to evaluate the impact of the various geometric positions of the tunnel on the thickness of the shotcrete shell. Exhaustive finite element simulations were carried out and the mechanical and geometric data of the shotcrete shell were determined for the first time by a large series of tests in situ. A statistic analysis verified the required thickness of the shotcrete shell on the basis of probabilistic observations. The study also examined whether the thickness of the shotcrete used on the exploratory tunnel would also be sufficient if the tunnel were in an off‐center position (including underneath the main tunnels) or for an additional tunnel running down the center axis.
Nichotherapy for stem cells: There goes the neighborhood
Authors: Levesque Jean‐Pierre , Winkler Ingrid G. , Rasko John E. J.
Published: November 2012

Stem cells and their malignant counterparts require the support of a specific microenvironment or “niche”. While various anti‐cancer therapies have been broadly successful, there are growing opportunities to target the environment in which these cells reside to further improve therapeutic efficacy and outcome. This is particularly true when the aim is to target normal or malignant stem cells. The field aiming to target or use the niches that harbor, protect, and support stem cells could be designated as “nichotherapy”. In this essay, we provide a few examples of nichotherapies. Some have been employed for decades, such as hematopoietic stem cell mobilization, whereas others are emerging, such as chemosensitization of leukemia stem cells by targeting their niche.
Analytical approach to determine biogenic amines in urine using microextraction in packed syringe and liquid chromatography coupled to electrochemical detection
Authors: Oppolzer David , Moreno Ivo , da Fonseca Beatriz , Passarinha Luís , Barroso Mário , Costa Suzel , Queiroz João António , Gallardo Eugenia
Published: November 2012

The goal of this work was to develop and validate an analytical method for the detection and quantification of the biogenic amines serotonin (5‐HT), dopamine (DA) and norepinephrine (NE), using microextraction in packed syringe (MEPS) and liquid chromatography coupled to electrochemical detection (HPLC‐ED) in urine. The method was validated according to internationally accepted guidelines from the Food and Drug Administration. Linearity was established between 50 and 1000 ng/mL for 5‐HT and between 5 and 1000 ng/mL for DA and NE, with determination coefficients (R2) >0.99 for all compounds. The limits of quantification and detection were respectively 50 and 20 ng/mL for 5‐HT, and 5 and 2 ng/mL for DA and NE. Within‐ and between‐run precision ranged from 0.84 to 9.41%, while accuracy ranged from 0.79 to 12.76% for all compounds. The intermediate precision and accuracy were 1.50–8.36 and 0.54–13.51%, respectively. The method was found suitable for clinical routine analysis of the studied compounds, using a sample volume of 0.5 mL. This is the first study employing a commercially available MEPS column for the simultaneous detection and quantification of 5‐HT, DA and NE in urine by coulometric detection. Copyright © 2012 John Wiley & Sons, Ltd.
High‐resolution MRI of basilar atherosclerosis: three‐dimensional acquisition and FLAIR sequences
Authors: Turan Tanya N. , Rumboldt Zoran , Brown Truman R.
Published: November 2012

This case report describes the use of high‐resolution magnetic resonance imaging (HRMRI) to visualize basilar artery atherosclerotic plaque in a patient with a pontine stroke. HRMRI with three‐dimensional image acquisition was used to visualize plaque in several planes to localize arterial wall pathology. Fluid attenuated inversion recovery (FLAIR) sequences of the basilar artery showed wall thickening throughout the basilar artery wall and good contrast between the artery wall and cerebrospinal fluid.
VEGF and bone cell signalling: an essential vessel for communication?
Authors: Clarkin Claire E. , Gerstenfeld Louis C.
Published: November 2012

Vascular endothelial growth factor (VEGF) is an endothelial cell survival factor and is required for effective coupling of angiogenesis and osteogenesis. Although central to bone homeostasis, repair and the pathobiology that affect these processes, the precise mechanisms coupling endothelial cell function within bone formation and remodelling remain unclarified. This review will (i) focus on the potential directionality of VEGF signalling in adult bone by identifying the predominant source of VEGF within the bone microenvironment, (ii) will summarize current VEGF receptor expression studies by bone cells and (iii) will provide evidence for a role for VEGF signalling during postnatal repair and osteoporosis. A means of understanding the directionality of VEGF signalling in adult bone would allow us to most effectively target angiogenic pathways in diseases characterized by changes in bone remodelling rates and enhance bone repair when compromised. Copyright © 2012 John Wiley & Sons, Ltd.
A Novel Photoaffinity‐Based Probe for Selective Detection of Cathepsin L Active Form
Authors: Torkar Ana , Bregant Sarah , Devel Laurent , Novinec Marko , Lenarčič Brigita , Lah Tamara , Dive Vincent
Published: November 2012

Detecting the active forms of proteases by using activity‐based probes in complex proteomes has become an intensively investigated field of research over the past years because many pathogenic conditions involve alterations in protease activities. The detection of lysosomal cysteine proteases, the cathepsins, has mostly relied on the use of probes that incorporate reactive electrophilic moieties to modify a cysteine in the active site covalently. Here we report the first example of an activity‐based probe that targets the cathepsins and incorporates a photoactivatable benzophenone group for covalent labelling. When tested on a set of five cathepsins (B, K, L, S and V), this probe selectively labelled the active site of cathepsin L. Furthermore, when tested on crude cell extracts, the probe specifically detected cathepsin L quantities as low as a few picomoles. This study suggests that photoaffinity labelling is a promising approach for developing highly selective and useful cathepsin L probes. In particular, this probe might allow the detection of small amounts of the secreted active cathepsin L form in the cellular microenvironment in vitro and ex vivo.
Dimethylarginine‐Dimethylaminohydrolase‐2 (DDAH‐2) Does Not Metabolize Methylarginines
Authors: Altmann Karin S. , Havemeyer Antje , Beitz Eric , Clement Bernd
Published: November 2012

Free endogenous methylarginines, Nω‐monomethyl‐L‐arginine (L‐NMMA) and Nω,Nω′‐dimethyl‐L‐arginine (ADMA), inhibit NO synthases (NOSs) and are metabolized by dimethylargininedimethylaminohydrolase (DDAH). A postulated metabolism has been shown several times for DDAH‐1, but the involvement of DDAH‐2 in the degradation of ADMA and L‐NMMA is still a matter of debate. Determination of the isoform‐specific DDAH protein expression profiles in various porcine tissue types shows a correlation of DDAH activity only with DDAH‐1 levels. DDAH activity (measured as L‐citrulline formation from the conversion of methylarginines and alternative DDAH substrates) was detected in DDAH‐1‐rich porcine tissue types, that is, kidney, liver, and brain, but not in DDAH‐2‐rich porcine fractions, that is, spleen and thyroid. Furthermore, several ex vivo studies showed DDAH activity to be important for L‐citrulline formation in porcine tissue and indicated the absence of an endogenous DDAH inhibitor in porcine tissue. This study provides new insights into tissue distributions as well as substrate selectivity for both DDAH isoforms. Although DDAH‐1 is known to metabolize the endogenous NOS inhibitors L‐NMMA and ADMA, a physiological function for DDAH‐2 has yet to be determined. Hence, determining DDAH activity by methylarginine conversion is not suitable for analyzing isoform selectivity of DDAH‐1 inhibitors as postulated.
A Simple Route to Synthesize Mesoporous ZSM‐5 Templated by Ammonium‐Modified Chitosan
Authors: Jin Junjiang , Zhang Xingdi , Li Yongsheng , Li Hua , Wu Wei , Cui Yunlong , Chen Qian , Li Liang , Gu Jinlou , Zhao Wenru , Shi Jianlin
Published: November 2012

Uniform mesoporous zeolite ZSM‐5 crystals have been successfully fabricated through a simple hydrothermal synthetic method by utilizing ammonium‐modified chitosan and tetrapropylammonium hydroxide (TPAOH) as the meso‐ and microscale template, respectively. It was revealed that mesopores with diameters of 5–20 nm coexisted with microporous network within mesoporous ZSM‐5 crystals. Ammonium‐modified chitosan was demonstrated to serve as a mesoporogen, self‐assembling with the zeolite precursor through strong static interactions. As expected, the prepared mesoporous ZSM‐5 exhibited greatly enhanced catalytic activities compared with conventional ZSM‐5 and Al‐MCM‐41 in reactions involving bulky molecules, such as the Claisen–Schmidt condensation of 2‐hydroxyacetophenone with benzaldehyde and the esterification reaction of dodecanoic acid and 2‐ethylhexanol.
Triazole‐Based One‐Dimensional Spin‐Crossover Coordination Polymers
Authors: Roubeau Olivier
Published: November 2012

One‐dimensional coordination FeII polymers constructed through triple N1,N2‐1,2,4‐triazole bridges form a unique class of spin‐crossover materials, the synthetic versatility of which allows tuning the spin‐crossover properties, the design of gels, films, liquid crystals, and nanoparticles and single‐particle addressing. This Minireview provides the first complete overview of these very attractive switchable materials and their most recent developments.
Amycolamicin: A Novel Broad‐Spectrum Antibiotic Inhibiting Bacterial Topoisomerase
Authors: Sawa Ryuichi , Takahashi Yoshiaki , Hashizume Hideki , Sasaki Kazushige , Ishizaki Yoshimasa , Umekita Maya , Hatano Masaki , Abe Hikaru , Watanabe Takumi , Kinoshita Naoko , Homma Yoshiko , Hayashi Chigusa , Inoue Kunio , Ohba Syunichi , Masuda Toru , Arakawa Masayuki , Kobayashi Yoshihiko , Hamada Masa , Igarashi Masayuki , Adachi Hayamitsu , Nishimura Yoshio , Akamatsu Yuzuru
Published: November 2012

The abuse of antibacterial drugs imposes a selection pressure on bacteria that has driven the evolution of multidrug resistance in many pathogens. Our efforts to discover novel classes of antibiotics to combat these pathogens resulted in the discovery of amycolamicin (AMM). The absolute structure of AMM was determined by NMR spectroscopy, X‐ray analysis, chemical degradation, and modification of its functional groups. AMM consists of trans‐decalin, tetramic acid, two unusual sugars (amycolose and amykitanose), and dichloropyrrole carboxylic acid. The pyranose ring named as amykitanose undergoes anomerization in methanol. AMM is a potent and broad‐spectrum antibiotic against Gram‐positive pathogenic bacteria by inhibiting DNA gyrase and bacterial topoisomerase IV. The target of AMM has been proved to be the DNA gyrase B subunit and its binding mode to DNA gyrase is different from those of novobiocin and coumermycin, the known DNA gyrase inhibitors.
Precocious hand use preference in reach‐to‐eat behavior versus manual construction in 1‐ to 5‐year‐old children
Authors: Sacrey Lori‐Ann R. , Arnold Benjamin , Whishaw Ian Q. , Gonzalez Claudia L.R.
Published: November 2012

The variation in hand use as a function of task and developmental age poses a problem for understanding how and when “handedness,” preferred use of one hand, develops. The present cross‐section study is the first to contrast hand preference use for the natural and frequently used reach‐to‐eat movement with a constructional task that requires a very similar reach‐to‐grasp movement. Thirty children between the ages of 1 and 3 years completed an eating task, in which they grasped small food items (Cheerios™ or Froot Loops™) that they brought to the mouth for eating. Thirty children between the ages of 3 and 5 years completed the construction task, in which they grasped LEGO® pieces to construct 3D models. Hand use preference for grasping in the eating and construction tasks was calculated by comparing the percentage of grasps made by the right hand and by the left hand. There were two main findings: First, right hand preference for grasping in the eating task is present as early as 1 year of age, whereas right hand preference for grasping in the construction task does not develop until 4 years of age. Second, right hand preference for grasping is greater in the eating than in the construction task. The results are discussed in relation to the idea that a consideration for task constraints (e.g., unimanual vs. bimanual; eating vs. construction; natural vs. praxic) should be incorporated into the experimental design when measuring hand use in children. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 902–911, 2013.
Effects of saline water drip irrigation on soil salinity and cotton growth in an Oasis Field
Authors: Hu Shunjun , Shen Yanjun , Chen Xiulong , Gan Yongde , Wang Xinfan
Published: November 2012

Using brackish and saline water is one of the most effective ways to solve the problem of water resource shortage. To rationally exploit and make use of brackish and saline water resources, the effects of drip irrigation underneath a plastic film with different salinities of irrigation water on soil salt content and cotton growth were studied at the Aksu National Field Research Station of Agro‐ecosystem in Xinjiang from 2008 to 2009. The results showed that the soil salt increases before the first irrigation of the growing period, then generally decreases during the irrigation period, and increases after the final irrigation of the growing period and before winter irrigation. In extremely arid areas, the leaching effect of rainfall is weakened. When cotton is irrigated with saline water of salinity greater than 2·24 g l−1, the salt is accumulated at the main cotton root zone. The effect of salinity of irrigation water on cotton growth is a gradual process and is highlighted during the boll‐opening period. Leaf area index, root area index, root length density, and root weight density all decrease with an increase of salinity of irrigation water and soil salt content in the root zone. The root weight density and root length density of treatments with brackish or saline water are far less than those of treatment with fresh water. After sowing, with the increase of time, the leaf area index changes from small to large, reaches its peak at the flowering‐bolling stage, and then reverts from large to small; however, root area index, average cotton root length density, and root weight density of the 0‐ to 50‐cm soil layer continuously increase throughout the entire process. During the boll‐opening period, the vitality of the cotton root remains strong. Copyright © 2012 John Wiley & Sons, Ltd.
Refusing to apologize can have psychological benefits (and we issue no mea culpa for this research finding)
Authors: Okimoto Tyler G. , Wenzel Michael , Hedrick Kyli
Published: November 2012

Despite an understanding of the perception and consequences of apologies for their recipients, little is known about the consequences of interpersonal apologies, or their denial, for the offending actor. In two empirical studies, we examined the unexplored psychological consequences that follow from a harm‐doer's explicit refusal to apologize. Results showed that the act of refusing to apologize resulted in greater self‐esteem than not refusing to apologize. Moreover, apology refusal also resulted in increased feelings of power/control and value integrity, both of which mediated the effect of refusal on self‐esteem. These findings point to potential barriers to victim–offender reconciliation after an interpersonal harm, highlighting the need to better understand the psychology of harm‐doers and their defensive behavior for self‐focused motives. Copyright © 2012 John Wiley & Sons, Ltd.
Lithospheric thinning and reworking of Late Archean juvenile crust on the southern margin of the North China Craton: evidence from the Longwangzhuang Paleoproterozoic A‐type granites and their surrounding Cretaceous adakite‐like granites
Authors: Wang Xiao‐Lei , Jiang Shao‐Yong , Dai Bao‐Zhang , Kern Jim
Published: November 2012

In the Longwangzhuang area along the southern margin of the North China Craton (NCC), a layer of Cretaceous K‐feldspar granites surrounds Paleoproterozoic granites. The Paleoproterozoic granites are enriched in sodic ferrogedrite and show low Al2O3 (12.3–13.0 wt%) and aluminum saturation index (ASI) (0.93–1.09) with high Zr (609–966 ppm), Y (47.2–96.7 ppm) and Nb (58.7–97.7 ppm) concentrations, resembling A‐type granites. The Cretaceous K‐feldspar granites have relatively high Sr (145–419 ppm), Ba (1252–1660 ppm), Sr/Y (19–127), La/Yb (36–56) ratios, but low Y (4.01–8.88 ppm) and Yb (0.46–0.99 ppm), geochemically resembling adakite‐like rocks. However, these Cretaceous adakite‐like K‐feldspar granites have rather low MgO (0.08–0.26 wt%), Al2O3 (13.6–14.5 wt%), Mg# (11–23), Cr (2.30–4.61 ppm) and high initial 86Sr/87Sr (0.7098–0.7118), as well as abundant K‐feldspar minerals, and are different from typical adakite. Zircon LA–ICP–MS geochronology shows that the two types of granites investigated in this study formed at 1616 ± 20 Ma and 140 ± 1 Ma, respectively. However, zircons from both the Paleoproterozoic and Cretaceous granites yield similar two‐stage Hf model ages at ca. 2.5–2.6 Ga, suggesting the reworking of Late Archean juvenile crust. The Paleoproterozoic A‐type granites show enriched Nd–Hf isotopic features but high whole‐rock oxygen isotopes. These rocks may have formed from partial melting of restitic crustal material during lithospheric thinning, along with extension and experienced crystal fractionation of plagioclase, apatite and magnetite. The Cretaceous adakite‐like K‐feldspar granites were formed by local anatexis of TTG rocks from the Taihua Group, with amphibole as the major residual phase. The local anatexis and accompanying migmatisation suggest crustal compression and possible transpression. Therefore, the lithospheric thinning in the NCC should have taken place after 140 Ma on the southern margin of the NCC. Copyright © 2012 John Wiley & Sons, Ltd.
Age‐related effect of serotonin transporter genotype on amygdala and prefrontal cortex function in adolescence
Authors: Wiggins Jillian Lee , Bedoyan Jirair K. , Carrasco Melisa , Swartz Johnna R. , Martin Donna M. , Monk Christopher S.
Published: November 2012

The S and LG alleles of the serotonin transporter‐linked polymorphic region (5‐HTTLPR) lower serotonin transporter expression. These low‐expressing alleles are linked to increased risk for depression and brain activation patterns found in depression (increased amygdala activation and decreased amygdala–prefrontal cortex connectivity). Paradoxically, serotonin transporter blockade relieves depression symptoms. Rodent models suggest that decreased serotonin transporter in early life produces depression that emerges in adolescence, whereas decreased serotonin transporter that occurs later in development ameliorates depression. However, no brain imaging research has yet investigated the moderating influence of human development on the link between 5‐HTTLPR and effect‐related brain function. We investigated the age‐related effect of 5‐HTTLPR on amygdala activation and amygdala–prefrontal cortex connectivity using a well‐replicated probe, an emotional face task, in children and adolescents aged 9–19 years. A significant genotype‐by‐age interaction predicted amygdala activation, such that the low‐expressing genotype (S/S and S/LG) group showed a greater increase in amygdala activation with age compared to the higher expressing (LA/LA and S/LA) group. Additionally, compared to the higher expressing group, the low‐expressing genotype group exhibited decreased connectivity between the right amygdala and ventromedial prefrontal cortex with age. Findings indicate that low‐expressing genotypes may not result in the corticolimbic profile associated with depression risk until later adolescence. Hum Brain Mapp 35:646–658, 2014. © 2012 Wiley‐Periodicals, Inc.
Three‐dimensional surface deformation‐based shape analysis of hippocampus and caudate nucleus in children with fetal alcohol spectrum disorders
Authors: Joseph Jesuchristopher , Warton Christopher , Jacobson Sandra W. , Jacobson Joseph L. , Molteno Chris D. , Eicher Anton , Marais Patrick , Phillips Owen R. , Narr Katherine L. , Meintjes Ernesta M.
Published: November 2012

Surface deformation‐based analysis was used to assess local shape variations in the hippocampi and caudate nuclei of children with fetal alcohol spectrum disorders. High‐resolution structural magnetic resonance imaging images were acquired for 31 children (19 controls and 12 children diagnosed with fetal alcohol syndrome/partial FAS). Hippocampi and caudate nuclei were manually segmented, and surface meshes were reconstructed. An iterative closest point algorithm was used to register the template of one control subject to all other shapes in order to capture the true geometry of the shape with a fixed number of landmark points. A point distribution model was used to quantify the shape variations in terms of a change in co‐ordinate positions. Using the localized Hotelling T2 method, regions of significant shape variations between the control and exposed subjects were identified and mapped onto the mean shapes. Binary masks of hippocampi and caudate nuclei were generated from the segmented volumes of each brain. These were used to compute the volumes and for further statistical analysis. The Mann–Whitney test was performed to predict volume differences between the groups. Although the exposed and control subjects did not differ significantly in their volumes, the shape analysis showed the hippocampus to be more deformed at the head and tail regions in the alcohol‐exposed children. Between‐group differences in caudate nucleus morphology were dispersed across the tail and head regions. Correlation analysis showed associations between the degree of compression and the level of alcohol exposure. These findings demonstrate that shape analysis using three‐dimensional surface measures is sensitive to fetal alcohol exposure and provides additional information than volumetric measures alone. Hum Brain Mapp 35:659–672, 2014. © 2012 Wiley Periodicals, Inc.
Intrinsic connectivity between the hippocampus, nucleus accumbens, and ventral tegmental area in humans
Authors: Kahn I. , Shohamy D.
Published: November 2012

Recent studies suggest that memory formation in the hippocampus is modulated by the motivational significance of events, allowing past experience to adaptively guide behavior. The effects of motivation on memory are thought to depend on interactions between the hippocampus, the ventral tegmental area (VTA), and the nucleus accumbens (NAcc). Indeed, animal studies reveal anatomical pathways for circuit‐level interaction between these regions. However, a homologue circuit connectivity in humans remains to be shown. We characterized this circuitry in humans by exploiting spontaneous low‐frequency modulations in the fMRI signal (termed resting‐state functional connectivity), which are thought to reflect functionally related regions and their organization into functional networks in the brain. We examined connectivity in this network across two datasets (hi‐resolution, n = 100; standard resolution, n = 894). Results reveal convergent connectivity between the hippocampus, and both the NAcc and the VTA centered on ventral regions in the body of the hippocampus. Additionally, we found individual differences in the strength of connectivity within this network. Together, these results provide a novel task‐independent characterization of circuitry underlying interactions between the hippocampus, NAcc, and VTA and provide a framework with which to understand how connectivity might reflect and constrain the effects of motivation on memory. © 2012 Wiley Periodicals, Inc.
Diabetes in Kyrgyzstan: changes between 2002 and 2009
Authors: Beran David , Abdraimova Aida , Akkazieva Baktygul , McKee Martin , Balabanova Dina , Yudkin John S
Published: November 2012

Health system reform in Kyrgyzstan is seen as a relative success story in central Asia. Initially, most attention focused on structural changes, and it is only since 2006 that the delivery of care and the experience of health service users have risen on the agenda. One exception from the earlier period was a rapid appraisal of the management of diabetes, undertaken in 2002. Using that study as a baseline, we describe the findings of a new evaluation of diabetes management, undertaken in 2009, using the Rapid Assessment Protocol for Insulin Access, now implemented in seven countries. Access to care has improved through the creation of the Family Medical Centres and the deployment of endocrinologists to them. Another improvement is the access to insulin and related medicines, although assessment of the procurement system reveals that the government is getting very poor value for money. Looking ahead, there are grounds for optimism that the passage of the law on diabetes may progressively have a greater impact. Although the law is not yet fully implemented, it has enabled the diabetes associations to defend the rights of their members. This increased capacity is credited with some improvements in diabetes care.

Copyright © 2012 John Wiley & Sons, Ltd.
MAGE‐A10 cancer/testis antigen is highly expressed in high‐grade non‐muscle‐invasive bladder carcinomas
Authors: Mengus Chantal , Schultz‐Thater Elke , Coulot Julie , Kastelan Zeljko , Goluza Eleonora , Coric Marijana , Spagnoli Giulio C. , Hudolin Tvrtko
Published: November 2012

Bladder cancer is a common urinary malignancy and a prevalent cause of cancer‐related death. Current therapies of early stage non‐muscle‐invasive bladder cancer (NMIBC) are frequently associated with undesirable toxicities and recurrence. Active antigen‐specific immunotherapy may provide a valid therapeutic option for patients with NMIBC. Cancer‐testis antigens (CTA) expressed in various tumour types and in a limited range of healthy tissues may represent potential targets for specific immunotherapy. MAGE‐A10 is probably the most immunogenic antigen of the MAGE‐A family. We evaluated the expression of MAGE‐A10 in NMIBC. Seventy‐nine patients undergoing surgical treatment for NMIBC were enrolled in the study. MAGE‐A10 gene expression was assessed by quantitative real‐time polymerase chain reaction. Immunohistochemistry was performed on paraffin‐embedded sections. MAGE‐A10 gene was specifically expressed in one‐third of NMIBC (n = 24: 32.43%). Gene expression was correlated with high tumour grade. MAGE‐A10 protein was exclusively detectable in nuclei of tumour cells. More importantly, MAGE‐A10 protein was also more frequently detectable in high‐grade tumours (p = 0.0001) and in stage T1 tumours invading subepithelial tissue or lamina propria (p = 0.01). A strong correlation between MAGE‐A10 staining score and tumour grade and stage could accordingly be observed. These data indicate that MAGE‐A10 expression is a feature of aggressive NMIBC and might be used as a novel target for specific immunotherapy of these cancers.
Inhibition of leydig tumor growth by farnesoid X receptor activation: The in vitro and in vivo basis for a novel therapeutic strategy
Authors: Catalano Stefania , Panza Salvatore , Malivindi Rocco , Giordano Cinzia , Barone Ines , Bossi Gianluca , Lanzino Marilena , Sirianni Rosa , Mauro Loredana , Sisci Diego , Bonofiglio Daniela , Andò Sebastiano
Published: November 2012

Leydig cell tumors (LCTs) are the most common tumors of the gonadal stroma and represent about 3% of all testicular neoplasms. In most cases, LCTs are benign; however, if the tumor is malignant, no effective treatments are currently available. We have recently reported that farnesoid X receptor (FXR) is expressed in R2C Leydig tumor cells, and it reduces the estrogen‐dependent cell proliferation by negatively regulating aromatase expression. Here, we demonstrated that treatment with GW4064, a specific FXR agonist, markedly reduced Leydig tumor growth in vivo by inhibiting proliferation and inducing apoptosis. Indeed, the tumors from GW4064‐treated mice exhibited a decrease in the expression of the proliferation marker Ki‐67 and aromatase along with an increase in the apoptotic nuclei. FXR activation induced an enhanced poly(ADP‐ribose) polymerase cleavage, a marked DNA fragmentation and a strong increase in TUNEL‐positive R2C cells also in vitro. Moreover, in both in vivo and in vitro models, FXR ligands upregulated mRNA and protein levels of p53 and of its downstream effector p21WAF1/Cip1. Functional experiments showed that FXR ligands upregulated p53 promoter activity and this occurred through an increased binding of FXR/nuclear factor‐kB (NF‐kB) complex to the NF‐kB site located within p53 promoter region as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation analysis. Taken together, results from our study show, for the first time, that treatment with FXR ligands induces Leydig tumor regression in vivo, suggesting that activation of FXR may represent a promising therapeutic strategy for LCTs.
Cancer cells preferentially lose small chromosomes
Authors: Duijf Pascal H.G. , Schultz Nikolaus , Benezra Robert
Published: November 2012

Genetic and genomic aberrations are the primary cause of cancer. Chromosome missegregation leads to aneuploidy and provides cancer cells with a mechanism to lose tumor suppressor loci and gain extra copies of oncogenes. Using cytogenetic and array‐based comparative genomic hybridization data, we analyzed numerical chromosome aneuploidy in 43,205 human tumors and found that 68% of solid tumors are aneuploid. In solid tumors, almost all chromosomes are more frequently lost than gained with chromosomes 7, 12 and 20 being the only exceptions with more frequent gains. Strikingly, small chromosomes are lost more readily than large ones, but no such inverse size correlation is observed with chromosome gains. Because of increasing levels of proteotoxic stress, chromosome gains have been shown to slow cell proliferation in a manner proportional to the number of extra gene copies gained. However, we find that the extra chromosome in trisomic tumors does not preferentially have a low gene copy number, suggesting that a proteotoxicity‐mediated proliferation barrier is not sustained during tumor progression. Paradoxically, despite a bias toward chromosome loss, gains of chromosomes are a poor prognostic marker in ovarian adenocarcinomas. In addition, we find that solid and non‐solid cancers have markedly distinct whole‐chromosome aneuploidy signatures, which may underlie their fundamentally different etiologies. Finally, preferential chromosome loss is observed in both early and late stages of astrocytoma. Our results open up new avenues of enquiry into the role and nature of whole‐chromosome aneuploidy in human tumors and will redirect modeling and genetic targeting efforts in patients.
Enzymatic processing by MMP‐2 and MMP‐9 of wild‐type and mutated mouse β‐dystroglycan
Authors: Sbardella Diego , Inzitari Rosanna , Iavarone Federica , Gioia Magda , Marini Stefano , Sciandra Francesca , Castagnola Massimo , Van den Steen Philippe E. , Opdenakker Ghislain , Giardina Bruno , Brancaccio Andrea , Coletta Massimo , Bozzi Manuela
Published: November 2012

Dystroglycan (DG) is a membrane‐associated protein complex formed by two noncovalently linked subunits, α‐DG, a highly glycosylated extracellular protein, and β‐DG, a transmembrane protein. The interface between the two DG subunits, which is crucial to maintain the integrity of the plasma membrane, involves the C‐terminal domain of α‐DG and the N‐terminal extracellular domain of β‐DG. It is well known that under both, physiological and pathological conditions, gelatinases (i.e. MMP‐9 and/or MMP‐2) can degrade DG, disrupting the connection between the extracellular matrix and the cytoskeleton. However, the molecular mechanisms and the exact cleavage sites underlying these events are still largely unknown. In a previous study, we have characterized the enzymatic digestion of the murine β‐DG ectodomain by gelatinases, identifying a main cleavage site on the β‐DG ectodomain produced by MMP‐9. In this article, we have deepened the pattern of the β‐DG ectodomain digestion by MMP‐2 by using a combined approach based on SDS‐PAGE, Orbitrap, and HPLC‐ESI‐IT mass spectrometry. Furthermore, we have characterized the kineticparameters of the digestion of some β‐DG ectodomain mutants by gelatinases. © 2012 IUBMB IUBMB Life, 64(12): 988–994, 2012
Longitudinal differences in the mechanical properties of the thoracic aorta depend on circumferential regions
Authors: Kim Jungsil , Hong Jung‐Wuk , Baek Seungik
Published: November 2012

Understanding the mechanical behavior of the arterial wall and its spatial variations is essential for the study of vascular physiopathology and the design of biomedical devices that interact with the arterial wall. Although it is generally accepted that the aortic wall gets stiffer along its length, the spatial variations in the mechanical behavior of the thoracic aorta are not well understood. In this study, therefore, we investigate both longitudinal and circumferential variations in the mechanical properties of the porcine descending thoracic aorta. Using a previously developed experimental method and stress–strain analysis, the stress, stretch, tangent modulus (TM), and pressure–strain elastic modulus (PSEM) are estimated in the range of in vivo pressure. The results show that the longitudinal differences of both TM and PSEM are statistically significant in the posterior region but not in the anterior region. Both moduli are greater in the posterior distal region when compared with the other test regions. The findings of this study meet a need for clarifying the region investigated, especially in circumferential region, to study the regional variations in biomechanics of blood vessels. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Characterization of hyaluronan–methylcellulose hydrogels for cell delivery to the injured spinal cord
Authors: Caicco Matthew J. , Zahir Tasneem , Mothe Andrea J. , Ballios Brian G. , Kihm Anthony J. , Tator Charles H. , Shoichet Molly S.
Published: November 2012

No effective clinical treatment currently exists for traumatic spinal cord injury. Cell replacement therapy holds promise for attaining functional repair. Cells may be delivered directly or near the injury site; however, this strategy requires a delivery vehicle to maintain cell viability. We have identified an injectable, biocompatible, and biodegradable hydrogel scaffold composed of hyaluronan (HA) and methylcellulose (MC) that may be an effective scaffold for therapeutic cell delivery. The purpose of the present study was to determine the effects of polymer concentration on HAMC mechanical strength, gelation time, and cell viability. The yield stress of HAMC, a measure of mechanical stiffness, was tunable via manipulation of MC and HA content. Measurement of the elastic and storage moduli as functions of time revealed that HAMC gels in less than 5 min at physiological temperatures. Human umbilical tissue‐derived cells encapsulated in HAMC were homogenously and stably distributed over 3 days in culture and extended processes into the scaffold. Cell viability was stable over this period in all but the most concentrated HAMC formulation. Because of its strength‐tunability, rapid gelation, and ability to maintain cell viability, HAMC is a promising vehicle for cell delivery and is being tested in ongoing in vivo studies. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets
Authors: Wöhrle Simon , Henninger Christine , Bonny Olivier , Thuery Anne , Beluch Noemie , Hynes Nancy E , Guagnano Vito , Sellers William R , Hofmann Francesco , Kneissel Michaela , Graus Porta Diana
Published: November 2012

Fibroblast growth factor 23 (FGF23) is a circulating factor secreted by osteocytes that is essential for phosphate homeostasis. In kidney proximal tubular cells FGF23 inhibits phosphate reabsorption and leads to decreased synthesis and enhanced catabolism of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Excess levels of FGF23 cause renal phosphate wasting and suppression of circulating 1,25(OH)2D3 levels and are associated with several hereditary hypophosphatemic disorders with skeletal abnormalities, including X-linked hypophosphatemic rickets (XLH) and autosomal recessive hypophosphatemic rickets (ARHR). Currently, therapeutic approaches to these diseases are limited to treatment with activated vitamin D analogues and phosphate supplementation, often merely resulting in partial correction of the skeletal aberrations. In this study, we evaluate the use of FGFR inhibitors for the treatment of FGF23-mediated hypophosphatemic disorders using NVP-BGJ398, a novel selective, pan-specific FGFR inhibitor currently in Phase I clinical trials for cancer therapy. In two different hypophosphatemic mouse models, Hyp and Dmp1-null mice, resembling the human diseases XLH and ARHR, we find that pharmacological inhibition of FGFRs efficiently abrogates aberrant FGF23 signaling and normalizes the hypophosphatemic and hypocalcemic conditions of these mice. Correspondingly, long-term FGFR inhibition in Hyp mice leads to enhanced bone growth, increased mineralization, and reorganization of the disturbed growth plate structure. We therefore propose NVP-BGJ398 treatment as a novel approach for the therapy of FGF23-mediated hypophosphatemic diseases. © 2013 American Society for Bone and Mineral Research.