bluuebunny/crossref_metadata_2025 huggingface dataset:
‘They Always Seem to be Angry’: The Cronulla Riot and the Civilising Pleasures of the Sun
Authors: Lattas Andrew
Published: February 2009

Contemporary ethnic rivalries often deny participation in racism and instead use the language of nationalism to formulate an etiquette of civility as defining national belonging. In contemporary Australia, world events such as the Bali Bombing, the 9/11 attacks and the Global War on Terror have empowered a civilisational logic, which often becomes localised to provide the moral terms for culturally ranking who has the capacity to participate in the pleasures of a modern enlightened nation. A culture of relaxation built around the beach, around the civilised enjoyment of the outdoors, is used as a point of contrast for a renewed Orientalism. It takes up breaches of everyday etiquette to create a psychological portrait of an uncivilised Arab Other who does not know how to relax and be peaceful.
Fire, Flood, Fish and the Uncertainty Paradox
Authors: Minnegal Monica , Dwyer Peter D.
Published: February 2009

When the planet was created, the areas of the greatest biodiversity also happened to be the areas where mankind wants to reap the best reward of resources. It is not actually that complicated when you think about it, because where there is biodiversity happens to be where the resources are and it is where we happen to want to get them from. As it happened, the uranium was put in the middle of Kakadu and gold is in places where it is hard to get out. I think the creator of the universe decided to make things very interesting for environment ministers down the track. That is the reality… It is only a natural thing. (Senator Ian Campbell, Federal Minister for the Environment; Hansard 2006: 68–69)
The Social Life of Rights: ‘Gender Antagonism’, Modernity and Raet in Vanuatu
Authors: Taylor John P.
Published: February 2009

In the northern Vanuatu town of Luganville a small group of men have responded to social and legal changes engendered by women's rights activists by forming a male support group called ‘Violence Against Men’. Members of this ‘backlash’ movement argue that the insidious promotion of Western‐style ‘women's rights’ is leading to discrimination against men in divorce proceedings, child custody battles, and in domestic violence and rape cases. They directly oppose recent and ongoing legal changes aimed at protecting women from domestic violence, such as Domestic Violence Protection Court Orders, and the repeatedly tabled (but long‐delayed) ‘Family Protection Bill’. Such interventions, they argue, undermine Vanuatu's ‘natural’kastom and Christian patriarchal gender order and, in doing so, pose a serious threat to the socio‐economic productivity of the nation‐state. For other men, however, rather than opposing women's rights activism, such challenges have raised questions about how men might successfully negotiate their identities in ways that are sensitive to contemporary issues of gender equality without undermining existing paradigms. Thus, this paper addresses the value accorded to universalism and relativism in gender activism in Vanuatu, and especially in terms of the linked discourses of kastom, church and modernity. It therefore explores gender relations in terms of the contemporary entanglement of indigenous and exogenous epistemologies, and in doing so argues that the contextual analysis of ‘rights’ should consider the specific historical, political and socio‐cultural circumstances in which they are put to use.
Police and Thieves, Gunmen and Drunks: Problems with Men and Problems with Society in Papua New Guinea
Authors: Macintyre Martha
Published: February 2009

The image of the ‘man with a gun’ is pervasive in Papua New Guinea and connotes not only the state's capacity to use force, but that of men to resist and subvert state control. At the same time, the association of beer and marijuana with both modernity and violent masculine behaviours provides the context, the justification and the forms of homosocial activities involving violence. In this paper, I explore the ambiguities surrounding guns as instruments of state force and as symbols of masculine autonomy in so‐called ‘weak states’ by examining some stories about the ways that guns are acquired for illegal activities. In particular, I shall discuss the ways that guns and beer are instruments of violence and potency for police, tribal warriors and criminals as well as some of the means whereby men gain access to new forms of power. Drawing on ethnographic research with young men in New Ireland Province, the paper will deal specifically with the ways that adolescent boys construe ‘modern masculinity’.
Sung Adornment: Changing Masculinities at Lake Kopiago, Papua New Guinea
Authors: Haley Nicole
Published: February 2009

In the space of 50 years, ideals of masculinity in the western end of the Southern Highlands have been radically transformed. Gone, for instance, is the bachelor cult where young boys were grown into men. Drawing upon ethnographic research undertaken over the past decade, in the Lake Kopiago sub‐district in the far north‐western corner of Southern Highlands Province, this paper seeks to document these changing masculinities and explore their portrayal by juxtaposing ‘traditional’ and contemporary growth enhancing spells and courting songs—particularly those composed and sung by men. In doing so, this paper also seeks to explore how guns, marijuana, discos and pornographic movies have come to figure centrally in contemporary notions of masculinity. It will also document how the proliferation of marijuana and small arms has transformed young men with otherwise very little standing in the community into self‐promoted leaders who have taken it upon themselves to publicly police the sexuality of women in increasingly violent ways.
In
Al
N
∕
Ga
N
metal-oxide-semiconductor high electron mobility transistor with Al2O3 insulating films grown by metal organic chemical vapor deposition using Ar and NH3 carrier gases
Authors: Čičo K. , Kuzmík J. , Liday J. , Hušeková K. , Pozzovivo G. , Carlin J.-F. , Grandjean N. , Pogany D. , Vogrinčič P. , Fröhlich K.
Published: February 2009

Al 2 O 3 thin films were deposited by a metal organic chemical vapour deposition on InAlN∕GaN heterostructures using Ar or NH3 as a carrier gas. Effects of NH3 and Ar carrier gases on the electrical and structural properties of Al2O3∕InAlN∕GaN HEMT devices were investigated by current voltage, current collapse, and Auger electron spectroscopy measurements. Al2O3 deposited using Ar as a carrier gas leads to a substantial gate leakage current reduction with no increase of the current collapse compare to Schottky gate based HEMT. On the other hand, HEMT electrical performance shows degradation if NH3 carrier gas is used. Similarly, Auger electron spectroscopy revealed presence of carbon on InAlN surface when NH3 carrier gas was applied. It is suggested that the formation of carbon-related traps on the InAlN surface takes place in the early stages of the Al2O3 deposition with NH3 carrier gas that strongly influences the HEMT performance.
On the band gaps and electronic structure of thin single crystalline praseodymium oxide layers on Si(111)
Authors: Seifarth O. , Dabrowski J. , Zaumseil P. , Müller S. , Schmeißer D. , Müssig H.-J. , Schroeder T.
Published: February 2009

The influence of stoichiometry and crystal structure on the electronic properties of single crystalline cubic PrO2(111), cubic Pr2O3(111), and hexagonal Pr2O3(0001) thin film heterostructures on Si(111) was investigated by synchrotron radiation based photoemission electron spectroscopy (PES) and x-ray absorption spectroscopy (XAS). A detailed analysis of the complex satellite structures of PES Pr 3d lines of the various Pr oxide phases is given. PES was in addition applied to study the O 2p derived valence band structure and the positions of the occupied Pr 4f state density. It is found by a combined PES-XAS study that especially the band gap values strongly depend on the stoichiometry and crystal structure of the single crystalline Pr oxide layer. Furthermore, the close structure relationship between cubic Pr2O3(111) and PrO2(111) films is probably the reason for the detection of nonstoichiometric behavior, an effect which is far less pronounced in case of hexagonal Pr2O3(0001) layers. A possible origin of this effect is given by a surface modified valence change and therefore of importance to understand in future the epitaxial overgrowth of these oxide buffer heterostructures by alternative semiconductors such as germanium.
Enhancement mode GaAs metal-oxide-semiconductor field-effect-transistor integrated with thin AlN surface passivation layer and silicon/phosphorus coimplanted source/drain
Authors: Gao Fei , Lee S. J. , Kwong D. L.
Published: February 2009

By using thin AlN film as a passivation layer between the GaAs and HfO2, GaAs metal-oxide-semiconductor (MOS) devices exhibited well-behaved accumulation and inversion capacitance-voltage characteristics with low leakage current of 6×10−5A∕cm2 at Vg=1V and interface state density of ∼4.9×1010cm−2eV−1. In order to improve the N+ source/drain activation efficiency, the Si∕P coimplantation technique was adapted to fabricate GaAs n-type metal-oxide-semiconductor field-effect-transistor (MOSFET). High quality N+∕P GaAs junction was achieved with extremely low junction leakage current of 3×10−6A∕cm2 at reverse bias of 1V and high forward current to reverse current ratio of Iforward∕Ireverse∼107 at GaAs source/drain junction. GaAs n-MOSFETs integrated with HfO2 gate dielectric and TaN gate electrode were fabricated by using AlN passivation layer and Si∕P coimplantation techniques. The results show that our GaAs n-MOSFETs operate in enhancement mode with Ion∕Ioff ratio of approximately six orders and good transfer and output characteristics.
REBL: A novel approach to high speed maskless electron beam direct write lithography
Authors: Petric Paul , Bevis Chris , Carroll Allen , Percy Henry , Zywno Marek , Standiford Keith , Brodie Alan , Bareket Noah , Grella Luca
Published: February 2009

The system concepts used in a novel approach for a high throughput maskless lithography system called reflective electron beam lithography (REBL) are described. The system is specifically targeting five to seven wafer levels per hour throughput on average at the 45nm node, with extendibility to the 32nm node and beyond. REBL incorporates a number of novel technologies to generate and expose lithographic patterns at estimated throughputs considerably higher than electron beam lithography has been able to achieve as yet. A patented reflective electron optic concept enables the unique approach utilized for the digital pattern generator (DPG). The DPG is a complementary metal oxide semiconductor application specific integrated circuit chip with an array of small, independently controllable metallic cells or pixels, which act as an array of electron mirrors. In this way, the system is capable of generating the pattern to be written using massively parallel exposure by ∼1×106 beams at extremely high data rates (∼1Tbit∕s compressed data). A rotary stage concept using a rotating platen carrying multiple wafers optimizes the writing strategy of the DPG.
Band bending and adsorption/desorption kinetics on N-polar GaN surfaces
Authors: Choi Soojeong , Kim Tong-Ho , Wu Pae , Brown April , Everitt Henry O. , Losurdo Maria , Bruno Giovanni
Published: February 2009

Highly reactive N-polar [000−1] GaN surfaces were analyzed using spectroscopic ellipsometry. Following exposure to air, observed changes in the pseudodielectric function near the GaN band edge indicate that surface contamination reduces the band bending. A subsequent Ga adsorption/desorption experiment on pristine N-polar GaN indicates that it contains a mixture of Ga-terminated and N-terminated surfaces. During deposition, Ga adatoms preferentially bond to the dangling bonds on the N-terminated surface: the measured 3.19 eV desorption activation energy equals the Ga–N decomposition energy. Further deposition forms a 1 ML Ga wetting layer whose 2.78 eV desorption activation energy is comparable to the Ga sublimation energy.
Transformation of polycrystalline tungsten to monocrystalline tungsten W(100) and its potential application in Schottky emitters
Authors: Dokania A. K. , Hendrikx Ruud , Kruit P.
Published: February 2009

The electron sources in electron microscopes and electron lithography machines often consist of small diameter W(100) wires, etched to form a sharp tip. The electron emission is facilitated by the Schottky effect, thus the name Schottky emitter. The authors are investigating the feasibility of arrays of such electron emitters for the use in multibeam lithography. This, however, would require large pieces of W(100) which are not easily available. The concept of dc Joule heating for the crystallographic transformation is utilized to convert polycrystalline tungsten to W(100) for the fabrication of the Schottky emitters. A miniature Schottky emitter fabricated by wire electrical discharge machining was heated by dc and the crystallographic orientation was subsequently determined by electron diffraction. The x-ray diffraction measurement on another sample of tungsten filament, heated by similar method, confirms the above results. The concept will be extended for the fabrication of a prototype multibeam source for parallel electron beam lithography.
The Mid-Atlantic Ridge Near 45 °N. XXII. Sedimentary Deposition and Lithogenesis on Mid-Atlantic Ridge Mountain Tops
Authors: Schafer Charles T.
Published: February 2009

Bottom photographs and drilled rock cores collected on several mountain tops along the crest of the Mid-Atlantic Ridge near 45°N describe the sediment distribution, sediment dynamics and shallow stratigraphy of these sites. Lag pebble deposits and pebble waves indicate rapid changes in bottom current direction and velocities that may approach 100 cm/s (>2 knots) one meter above the bottom so that surface sediments are often not indicative of sediment and rock types sampled using shallow drilling techniques. Absolute dates (14C) of coralline limestone, which underlies coarse unconsolidated sediment at most drilling sites, suggest deposition and initial lithification of these deposits during a middle Wisconsin interstadial period.
The Topsails igneous complex: Silurian–Devonian peralkaline magmatism in western Newfoundland
Authors: Taylor R. P. , Strong D. F. , Kean B. F.
Published: February 2009

The Topsails igneous complex of western Newfoundland is a large (> 6000 km2) intrusive complex of two contrasting geochemical suites and at least four distinct granitoid facies: (i) a fine-to medium-grained biotite-bearing peraluminous granite; (ii) a medium- to coarse-grained metaluminous biotite–hastingsite granite; (iii) a coarse-grained peralkaline aegirine-arfvedsonite granite; and (iv) fine- to medium-grained biotite-hornblende granites and syenites. Peralkaline microgranite dykes cut the other granitoid phases and the country rocks. Peralkaline granites occur within the central parts of the complex, the other granitoid phases being marginal. Volcanic and subvolcanic roof pendants are divisible into peralkaline and non-peralkaline groups. The former are clearly related to the peralkaline granite, and the latter appear to represent the other intrusive phases of the complex. Contemporaneous basalt magmatism is indicated by dykes which cut the biotite granites and are in turn cut by the peralkaline granite. Available Rb–Sr data show ages of 386 ± 9 and 419 ± 5 Ma for the peraluminous and peralkaline granites respectively.The main difference in major elements between the peralkaline and non-peralkaline granites is in their agpaiitic indices, although there is some overlap between them. There are, however, marked dissimilarities in their respective trace element characteristics, e.g., K/Rb, K/Zr, and Rb/Sr, with high Zn concentrations being especially characteristic of the peralkaline rocks.The origin of these rocks is interpreted in terms of a model involving crustal melting due to the interaction of crustal extension, basaltic intrusion, and volatile fluxing, with subsequent high-level intrusion and fractionation, along with metasomatism by magmatically-derived fluids.
Glacial geology of Grand Manan Island, New Brunswick
Authors: Legget Robert F.
Published: February 2009

Grand Manan is the largest of an archipelago of 20 islands at the mouth of the Bay of Fundy. Twenty-four kilometres long and 11 km wide, its western part consists of Triassic basalt with cliffs up to 120 m high. The eastern section consists of older rocks, is low lying, and is the site of the main settlements. Early scientific visitors thought that the island had escaped glaciation but there is abundant evidence to show that it did not, although the age of the last glaciation has not yet been established. Outwash and raised beach deposits are found throughout the island. Glacial striae show directions of ice movement ranging over 120°. Examples of multidirectional striae on the same rock surface have been observed. Isolated glacial erratics, some from the New Brunswick mainland, are found in the eastern part of the island, with one unusual assemblage on the south coast. A few exposures of till are described, one exhibiting two superposed tills of differing lithology, as known elsewhere in the Maritime Provinces. Carbon-14 dating of organic matter exposed at about half tide level and about 4 m above high tide level appears to agree with estimates of the changes of sea level during the last 16 000 years for other parts of the Maritime Provinces.
Crustal studies in the La Malbaie Region, Quebec
Authors: Lyons J. A. , Forsyth D. A. , Mair J. A.
Published: February 2009

The results of three seismological investigations of the crust in the seismically active La Malbaie Region are reported. First arrivals from a reversed reflection–refraction profile within the Charlevoix structure indicate a uniform Pg velocity of 6.08 ± 0.04 km/s. Secondary arrivals forming discontinuous, sometimes arcuate segments on the record sections are interpreted as subcritical reflections from structural contortions related to impact of the Charlevoix meteorite. A coherent event at 14 s may signal reflection from the M-discontinuity near 45 km depth.Analysis of travel times from calibration shots recorded by a network of stations spanning the St. Lawrence River in terms of time–distance profiles, travel time residuals, and numerical models provides excellent support for a model of the Precambrian–Paleozoic contact striking along the north shore and dipping to the southeast about 20° beneath the wedge of 5.5 km/s sediments.Unreversed profiles obtained by recording timed Thetford Mines blasts across a similar network suggests a comparable deep structure beneath the north and south shores, with average crustal velocities of 6.8 and 6.7 km/s, respectively. A minor mid-crustal discontinuity is suggested, and Moho depth is estimated at 42–43 km.The 6.2 km/s upper crustal velocity found for the crater and immediately surrounding area is anomalously low compared to the 6.4–6.5 km/s reported for the eastern shield region. Structural lineations gleaned from satellite imagery suggest an elongated area of impact-related disruption much larger than previously recognized. This expanded area of crustal weakening encompasses and may partially explain the zone of continuing microseismic activity, as well as the low upper crustal velocity of the La Malbaie Region.
Aphebian overprinting in the Superior Province east of James Bay, Quebec
Authors: Brooks C.
Published: February 2009

Layered gneisses and migmatite from the Superior Province east of James Bay, Quebec, provide a total-rock errorchron age of ca. 2300 Ma. This is interpreted as resulting from partial to complete isotopic reequilibration, on the scale of distinct layers, of Kenoran rocks during an Aphebian event. The total-rock errorchron has no direct age significance, and one possible geological explanation of the proposed "overprinting" links the data to a northerly, on-strike extrapolation of the Proterozoic Kapuskasing Belt.
SYNTHESIS, STRUCTURAL CHARACTERIZATION AND MAGNETIC BEHAVIOR OF RuSr2GdCu2O8/La0.67Sr0.33MnO3 COMPOSITES
Authors: CORREDOR L. T. , LANDÍNEZ TÉLLEZ D. A. , REYES O. M. C. , ROA-ROJAS J. , JURELO A. R. , PUREUR P.
Published: February 2009

In this work we report the synthesis of RuSr 2 GdCu 2 O 8/ La 0.67 Sr 0.33 MnO 3 superconducting-magnetic composites with 50 vol.% of both RuSr 2 GdCu 2 O 8 and La 0.67 Sr 0.33 MnO 3 compounds. Structural characterization was performed by X-ray diffraction, which permitted us to establish the absence of other crystallographic phases and the non-reactive character of the compounds into the composite. Scanning electron microscopy showed the sub-micrometric size of the grains. Energy dispersive X-ray experiments confirmed chemical stability between RuSr 2 GdCu 2 O 8 and La 0.67 Sr 0.33 MnO 3 compounds in the composites. Resistivity measurements provided evidence of superconducting transition for the RuSr 2 GdCu 2 O 8 material, with TSC=39.2 K. Results of magnetization as a function of temperature corroborated the superconducting transition and showed the expected antiferromagnetic character of the Ru perovskite, with a Néel temperature TN=132.7 K. Systematic measurements of applied magnetic field up to 5 kOe were performed at these temperature regimes: TN < T < TC (with TC being the Curie temperature of the La 0.67 Sr 0.33 MnO 3 compound); TSC < T < TN; and T < TSC. Our results reveal the ferromagnetic character of the composites at the temperature regime TN < T < TC. The exchange bias effect was observed for weak applied fields (H < 1.5 kOe) at temperatures between TSC < T < TN. At the superconducting regime (T < TSC) weaker exchange bias is observed for low magnetic fields (H < 1 kOe). For strong magnetic fields (H > 2 kOe) the ferromagnetic character of the system is recovered.
DYNAMICAL SUPPRESSION OF ENTANGLEMENT SUDDEN DEATH IN A JAYNES–CUMMINGS MODEL EXTENDED
Authors: YAN XUE-QUN
Published: February 2009

The Jaynes–Cummings model extended by the inclusion of mode structure and atomic motion is an elementary model that describes the interaction between a single atom and electromagnetic pulse. Based on the model, we explore the time evolution of the entanglement between two atoms, initially non-locally correlated and crossing separately two distinct cavities. Our results show that this model suggests a strategy to fight against the so-called entanglement sudden death, and in the situation resurrection of the original entanglement value occurs periodically and the entanglement will remain at the original value for a finite duration.
SUPPORTING FORMAL VERIFICATION OF DIMA MULTI-AGENTS MODELS: TOWARDS A FRAMEWORK BASED ON MAUDE MODEL CHECKING
Authors: BOUDIAF NOURA , MOKHATI FARID , BADRI MOURAD
Published: February 2009

Model Checking based verification techniques represent an important issue in the field of concurrent systems quality assurance. The lack of formal semantics in the existing formalisms describing multi-agents models combined with multi-agents systems complexity are sources of several problems during their development process. The Maude language, based on rewriting logic, offers a rich notation supporting formal specification and implementation of concurrent systems. In addition to its modeling capacity, the Maude environment integrates a Model Checker based on Linear Temporal Logic (LTL) for distributed systems verification. In this paper, we present a formal and generic framework (DIMA-Maude) supporting formal description and verification of DIMA multi-agents models.
A QUANTITATIVE-BASED COMPARISON OF MaSE AND OPM/MAS DESIGN RESULTS
Authors: STURM ARNON , TAIEB-MAIMOM MEIRAV , GOREN-BAR DINA
Published: February 2009

Many studies have compared the properties of agent-oriented methodologies, usually applying the qualitative approach. In contrast, the quantitative approach for comparing these methodologies has rarely been used. Thus, it is difficult to assess the extent of suitability of these methodologies to, and the understanding and usage of the methodologies by, their intended users. In this paper, we adopted a quantitative approach for the comparison of two agent-oriented modeling methods, the Multiagent System Engineering (MaSE) and the Object-Process Methodology for Multi-Agent Systems (OPM/MAS). In particular, we examined the modeling language of each method as reflected in the design results. The results of the examination highlighted the differences between the two methods. Specifically, MaSE was found to be more adequate for understanding interactions and in specifying a new behavior. On the other hand, OPM/MAS was found helpful in understanding the entire system and in specifying interactions with the environment. These results clearly indicate the improvements required for each of the methods compared.
EMPIRICAL EVALUATION AND VALIDATION OF INTERFACE COMPLEXITY METRICS FOR SOFTWARE COMPONENTS
Authors: SHARMA ARUN , KUMAR RAJESH , GROVER P. S.
Published: February 2009

The major drivers for complex applications are cost, efficiency, development time, understandability, usability and more importantly the maintainability. Due to their black box nature, complexity of software components is more crucial for component-based systems. This paper discusses various complexity concerns for these systems and reviews a number of complexity metrics for software components and component-based systems. As interfaces are the only source of information to know about the black-box components, this paper proposes a new interface complexity metric for these components. This metric is based on the information available in the interfaces like interface methods and properties. It also discusses the methodology to assign the weight values to these methods and properties to finally evaluate the complexity of the component. This paper validates the proposed metric against standard Weyukar's properties and empirically evaluates the metric for several Java Bean components. Finally a correlation analysis between proposed metrics and several other metrics like performance, customizability and readability is done to validate the metric.
Protease inhibitors used in the treatment of HIV+ induce β-cell apoptosis via the mitochondrial pathway and compromise insulin secretion
Authors: Zhang Sheng , Carper Michael J. , Lei Xiaoyong , Cade W. Todd , Yarasheski Kevin E. , Ramanadham Sasanka
Published: February 2009

Inclusion of HIV protease inhibitors (PIs) in the treatment of people living with HIV+ has markedly decreased mortality but also increased the incidence of metabolic abnormalities, causes of which are not well understood. Here, we report that insulinopenia is exacerbated when Zucker fa/fa rats are exposed to a PI for 7 wk, suggesting that chronic PI exposure adversely affects pancreatic islet β-cell function. In support of this possibility, we find increased apoptosis, as reflected by TUNEL fluorescence analyses, and reduced insulin-secretory capacity in insulinoma cells and human pancreatic islet cells after in vitro exposures (48–96 h) to clinically relevant PIs (ritonavir, lopinavir, atazanavir, or tipranavir). Furthermore, pancreatic islets isolated from rats administered an HIV-PI for 3 wk exhibit greater cell death than islets isolated from vehicle-administered rats. The higher incidence of HIV-PI-induced cell death was associated with cleavage and, hence, activation of caspase-3 and poly(ADP)-ribose polymerase but not with activation of phospho-pancreatic endoplasmic reticulum (ER) kinase or induction of ER stress apoptotic factor C/EBP homologous protein. Exposure to the HIV-PIs, however, led to activation of mitochondria-associated caspase-9, caused a loss in mitochondrial membrane potential, and promoted the release of cytochrome c, suggesting that HIV-PIs currently in clinically use can induce β-cell apoptosis by activating the mitochondrial apoptotic pathway. These findings therefore highlight the importance of considering β-cell viability and function when assessing loss of glycemic control and the course of development of diabetes in HIV+ subjects receiving a protease inhibitor.
The Lou/C rat: a model of spontaneous food restriction associated with improved insulin sensitivity and decreased lipid storage in adipose tissue
Authors: Veyrat-Durebex Christelle , Montet Xavier , Vinciguerra Manlio , Gjinovci Asllan , Meda Paolo , Foti Michelangelo , Rohner-Jeanrenaud Françoise
Published: February 2009

The inbred Lou/C rat, originating from the Wistar strain, has been described as a model of resistance to diet-induced obesity, but little is known about its metabolism. Since this knowledge could provide some clues about the etiology of obesity/insulin resistance, this study aimed at characterizing glucose and lipid metabolism in Lou/C vs. Wistar rats. This was achieved by performing glucose and insulin tolerance tests, euglycemic hyperinsulinemic clamps, and characterization of intracellular insulin signaling in skeletal muscle. Substrate-induced insulin secretion was evaluated using perfused pancreas and isolated islets. Finally, body fat composition and the expression of various factors involved in lipid metabolism were determined. Body weight and caloric intake were lower in Lou/C than in Wistar rats, whereas food efficiency was similar. Improved glucose tolerance of Lou/C rats was not related to increased insulin output but was related to improved insulin sensitivity/responsiveness in the liver and in skeletal muscles. In the latter tissue, this was accompanied by improved insulin signaling, as suggested by higher activation of the insulin receptor and of the Akt/protein kinase B pathway. Fat deposition was markedly lower in Lou/C than in Wistar rats, especially in visceral adipose tissue. In the inguinal adipose depot, expression of uncoupling protein-1 was detected in Lou/C but not in Wistar rats, in keeping with a higher expression of peroxisome proliferator-activated receptor-γ coactivator-1 in these animals. The Lou/C rat is a valuable model of spontaneous food restriction with associated improved insulin sensitivity. Independently from its reduced caloric intake, it also exhibits a preferential channeling of nutrients toward utilization rather than storage.
Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance
Authors: Davis J. Mark , Murphy E. Angela , Carmichael Martin D. , Davis Ben
Published: February 2009

Quercetin is one of a broad group of natural polyphenolic flavonoid substances that are being investigated for their widespread health benefits. These benefits have generally been ascribed to its combination of antioxidant and anti-inflammatory activity, but recent in vitro evidence suggests that improved mitochondrial biogenesis could play an important role. In addition, the in vivo effects of quercetin on mitochondrial biogenesis exercise tolerance are unknown. We examined the effects of 7 days of quercetin feedings in mice on markers of mitochondrial biogenesis in skeletal muscle and brain, and on endurance exercise tolerance. Mice were randomly assigned to one of the following three treatment groups: placebo, 12.5 mg/kg quercetin, or 25 mg/kg quercetin. Following 7 days of treatment, mice were killed, and soleus muscle and brain were analyzed for mRNA expression of peroxisome proliferator-activated receptor-γ coactivator (PGC-1α) and sirtuin 1 (SIRT1), and mitochondrial DNA (mtDNA) and cytochrome c. Additional mice underwent a treadmill performance run to fatigue or were placed in voluntary activity wheel cages, and their voluntary activity (distance, time, and peak speed) was recorded. Quercetin increased mRNA expression of PGC-1α and SIRT1 ( P < 0.05), mtDNA ( P < 0.05) and cytochrome c concentration ( P < 0.05). These changes in markers of mitochondrial biogenesis were associated with an increase in both maximal endurance capacity ( P < 0.05) and voluntary wheel-running activity ( P < 0.05). These benefits of querectin on fitness without exercise training may have important implications for enhancement of athletic and military performance and may also extend to prevention and/or treatment of chronic diseases.
Netrin-1 increases proliferation and migration of renal proximal tubular epithelial cells via the UNC5B receptor
Authors: Wang Weiwei , Reeves W. Brian , Ramesh Ganesan
Published: February 2009

The cellular hallmark of kidney repair is a rapid proliferation of renal tubular epithelial cells ultimately leading to the restoration of nephron structure and function. Netrin-1 was discovered as a neural guidance cue and found to be expressed outside the nervous system, including in kidney. Previous work showed that netrin-1 is upregulated in response to ischemic injury and ameliorates ischemic injury. The objectives of this study were to determine the role of netrin-1 in renal tubular epithelial cell proliferation and migration in vitro. Real-time RT-PCR analysis showed that netrin-1 and its receptors UNC5B and neogenin are highly expressed in cultured mouse renal epithelial cells (TKPTS), whereas the expression of the Deleted in Colon Cancer (DCC), UNC5A, UNC5C, and UNC5D receptors is negligible or undetectable. Netrin-1 protein was induced in the edges of mechanical wounds in vitro. Netrin-1 increased TKPTS cell proliferation in a dose-dependent manner. The netrin-1-induced increase in TKPTS cell proliferation was completely prevented by small interfering RNA (siRNA) inhibition of UNC5B receptor but not UNC5C receptor expression. Netrin-1 also increased TKPTS cell migration in vitro, and this was also mediated through the UNC5B receptor. Netrin-1 increased the phosphorylation of Akt and ERK. Inhibition of phosphatidylinositol 3-kinase and MEK1/2 completely inhibited netrin-1-induced cell proliferation but not migration. These results indicate that netrin-1 increases renal tubular epithelial cell proliferation and migration through the UNC5B receptor. Moreover, the increase in cell proliferation, but not migration, was mediated via activation of Akt and ERK pathways.
Using Light to Reinstate Respiratory Plasticity
Authors: Arenkiel Benjamin R. , Peca Joao
Published: February 2009

Restoring normal function to damaged or diseased nervous tissue remains a major goal of both basic and clinical neuroscience research. Advances in genetic technologies now allow targeted control of neuronal activity in the mammalian nervous system, providing novel therapeutic avenues to repair or bypass faulty circuits. Here we review recent work published in the Journal of Neuroscience by Alilain et al., demonstrating the use of Channelrhodopsin-2 to restore breathing in rodent models of spinal cord injury.
Identification of Cancer Stem Cells in Ewing's Sarcoma
Authors: Suvà Mario-Luca , Riggi Nicolò , Stehle Jean-Christophe , Baumer Karine , Tercier Stéphane , Joseph Jean-Marc , Suvà Domizio , Clément Virginie , Provero Paolo , Cironi Luisa , Osterheld Maria-Chiara , Guillou Louis , Stamenkovic Ivan
Published: February 2009

Cancer stem cells that display tumor-initiating properties have recently been identified in several distinct types of malignancies, holding promise for more effective therapeutic strategies. However, evidence of such cells in sarcomas, which include some of the most aggressive and therapy-resistant tumors, has not been shown to date. Here, we identify and characterize cancer stem cells in Ewing's sarcoma family tumors (ESFT), a highly aggressive pediatric malignancy believed to be of mesenchymal stem cell (MSC) origin. Using magnetic bead cell separation of primary ESFT, we have isolated a subpopulation of CD133+ tumor cells that display the capacity to initiate and sustain tumor growth through serial transplantation in nonobese diabetic/severe combined immunodeficiency mice, re-establishing at each in vivo passage the parental tumor phenotype and hierarchical cell organization. Consistent with the plasticity of MSCs, in vitro differentiation assays showed that the CD133+ cell population retained the ability to differentiate along adipogenic, osteogenic, and chondrogenic lineages. Quantitative real-time PCR analysis of genes implicated in stem cell maintenance revealed that CD133+ ESFT cells express significantly higher levels of OCT4 and NANOG than their CD133− counterparts. Taken together, our observations provide the first identification of ESFT cancer stem cells and demonstration of their MSC properties, a critical step towards a better biological understanding and rational therapeutic targeting of these tumors. [Cancer Res 2009;69(5):1776–81]
Vascular Cell Adhesion Molecule-1 Is a Regulator of Ovarian Cancer Peritoneal Metastasis
Authors: Slack-Davis Jill K. , Atkins Kristen A. , Harrer Christine , Hershey E. Daniel , Conaway Mark
Published: February 2009

Ovarian cancers metastasize by attaching to and invading through the mesothelium, a single layer of mesothelial cells lining the peritoneal cavity. The presence of invasive peritoneal metastases is associated with a poor prognosis for ovarian cancer (5-year survival <25%). Vascular cell adhesion molecule-1 (VCAM-1) is a cell surface receptor that mediates leukocyte attachment and extravasation across endothelial and mesothelial monolayers at sites of inflammation. Membranous VCAM-1 expression was observed on the mesothelium of 13 of 14 women with ovarian cancer compared with 6 of 15 who were cancer-free. Using a cell culture model system of mesothelial invasion, highly tumorigenic SKOV-3 and ES-2 cells were 2.5 to 3 times more efficient in transmigration through the mesothelial monolayer compared with poorly tumorigenic OVCAR-3 cells. Blocking antibodies to, or small interfering RNA knockdown of, VCAM-1 or its ligand α4β1 integrin significantly decreased, but did not completely inhibit, transmigration of SKOV-3 cells through mesothelial monolayers. Furthermore, using a mouse model of ovarian cancer metastasis, treatment with VCAM-1 function-blocking antibodies decreased tumor burden and increased survival. Together, these observations implicate VCAM-1-α4β1 integrin interactions in the regulation of ovarian cancer cell mesothelial invasion and metastatic progression and offer the possibility of novel therapeutic targets. [Cancer Res 2009;69(4):1469–76]
Serum Vitamin D and Risk of Pancreatic Cancer in the Prostate, Lung, Colorectal, and Ovarian Screening Trial
Authors: Stolzenberg-Solomon Rachael Z. , Hayes Richard B. , Horst Ron L. , Anderson Kristin E. , Hollis Bruce W. , Silverman Debra T.
Published: February 2009

Experimental evidence suggests that vitamin D has anticarcinogenic properties; however, a nested case-control study conducted in a population of male Finnish smokers found that higher 25-hydroxyvitamin D [25(OH)D], the best indicator of vitamin D status as determined by the sun and diet, was associated with a significant 3-fold increased risk for pancreatic cancer. We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Screening Trial cohort of men and women 55 to 74 years of age at baseline to test whether prediagnostic serum 25(OH)D concentrations were associated with pancreatic cancer risk. Between 1994 and 2006, 184 incident cases of pancreatic adenocarcinoma occurred (follow-up to 11.7 years). Two controls (n = 368) who were alive at the time the case was diagnosed were selected for each case and matched by age, race, sex, and calendar date of blood draw (to control for seasonal variation). We calculated odds ratios (OR) and 95% confidence intervals (95% CI) using conditional logistic regression, adjusting for smoking and body mass index. Vitamin D concentrations were not associated with pancreatic cancer overall (highest versus lowest quintile, >82.3 versus <45.9 nmol/L: OR, 1.45; 95% CI, 0.66–3.15; P trend = 0.49). However, positive associations were observed among subjects with low estimated annual residential solar UBV exposure, but not among those with moderate to high annual exposure (P interaction = 0.015). We did not confirm the previous strong positive association between 25(OH)D and pancreatic cancer; however, the increased risk among participants with low residential UVB exposure is similar. [Cancer Res 2009;69(4):1439–47
Selective Inhibition of Matrix Metalloproteinase-14 Blocks Tumor Growth, Invasion, and Angiogenesis
Authors: Devy Laetitia , Huang Lili , Naa Laurent , Yanamandra Niranjan , Pieters Henk , Frans Nicolas , Chang Edward , Tao Qingfeng , Vanhove Marc , Lejeune Annabelle , van Gool Reinoud , Sexton Daniel J. , Kuang Guannan , Rank Douglas , Hogan Shannon , Pazmany Csaba , Ma Yu Lu , Schoonbroodt Sonia , Nixon Andrew E. , Ladner Robert C. , Hoet Rene , Henderikx Paula , TenHoor Chris , Rabbani Shafaat A. , Valentino Maria Luisa , Wood Clive R. , Dransfield Daniel T.
Published: February 2009

Inhibition of specific matrix metalloproteinases (MMP) is an attractive noncytotoxic approach to cancer therapy. MMP-14, a membrane-bound zinc endopeptidase, has been proposed to play a central role in tumor growth, invasion, and neovascularization. Besides cleaving matrix proteins, MMP-14 activates proMMP-2 leading to an amplification of pericellular proteolytic activity. To examine the contribution of MMP-14 to tumor growth and angiogenesis, we used DX-2400, a highly selective fully human MMP-14 inhibitory antibody discovered using phage display technology. DX-2400 blocked proMMP-2 processing on tumor and endothelial cells, inhibited angiogenesis, and slowed tumor progression and formation of metastatic lesions. The combination of potency, selectivity, and robust in vivo activity shows the potential of a selective MMP-14 inhibitor for the treatment of solid tumors. [Cancer Res 2009;69(4):1517–26]
Integral Role of Transcription Factor 8 in the Negative Regulation of Tumor Angiogenesis
Authors: Inuzuka Takayuki , Tsuda Masumi , Tanaka Shinya , Kawaguchi Hideaki , Higashi Yujiro , Ohba Yusuke
Published: February 2009

Angiogenesis is involved in various physiologic and pathological conditions, including tumor growth, and is tightly regulated by the orchestration of proangiogenic and antiangiogenic factors. Inhibition of vascular endothelial growth factor (VEGF), the best-established antiangiogenic treatment in cancer, has shown some effectiveness; however, the identification of novel regulators, whose function is independent of VEGF, is required to achieve better outcomes. Here, we show that transcription factor 8 (TCF8) is up-regulated in endothelial cells during angiogenesis, acting as a negative regulator. Furthermore, TCF8 is specifically expressed in the endothelium of tumor vessels. Tcf8-heterozygous knockout mice are more permissive than wild-type mice to the formation of tumor blood vessels in s.c. implanted melanoma, which seems to contribute to the more aggressive growth and the lung metastases of the tumor in mutant mice. Suppression of TCF8 facilitates angiogenesis in both in vitro and ex vivo models, and displays comprehensive cellular phenotypes, including enhanced cell invasion, impaired cell adhesion, and increased cell monolayer permeability due to, at least partly, MMP1 overexpression, attenuation of focal adhesion formation, and insufficient VE-cadherin recruitment, respectively. Taken together, our findings define a novel, integral role for TCF8 in the regulation of pathologic angiogenesis, and propose TCF8 as a target for therapeutic intervention in cancer. [Cancer Res 2009;69(4):1678–84]
Reactivation of Suppressed RhoB is a Critical Step for the Inhibition of Anaplastic Thyroid Cancer Growth
Authors: Marlow Laura A. , Reynolds Lisa A. , Cleland Alan S. , Cooper Simon J. , Gumz Michelle L. , Kurakata Shinichi , Fujiwara Kosaku , Zhang Ying , Sebo Thomas , Grant Clive , McIver Bryan , Wadsworth J. Trad , Radisky Derek C. , Smallridge Robert C. , Copland John A.
Published: February 2009

Anaplastic thyroid carcinoma (ATC) is a highly aggressive form of the disease for which new therapeutic options are desperately needed. Previously, we showed that the high-affinity peroxisome proliferator–activated receptor γ (PPARγ) agonist, RS5444, inhibits cell proliferation of ATC cells via induction of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 (p21). We show here that up-regulation of RhoB is a critical step in PPARγ-mediated activation of p21-induced cell stasis. Using multiple independently derived ATC cell lines, we found that treatment with RS5444 leads to the up-regulation of RhoB and subsequent activation of p21, and that silencing of RhoB by RNAi blocks the ability of RS5444 to induce p21 and to inhibit cell proliferation. Our results show that transcriptional regulation of RhoB by the nuclear transcription factor PPARγ is responsible for the induction of p21 mRNA and protein. We further implicate RhoB as a key signaling effector for the growth inhibition of ATC, as treatment with a histone deacetylase inhibitor shown to increase RhoB expression in lung cancer cells caused the up-regulation of RhoB in ATC cells accompanied by increased expression of p21 and inhibition of cell proliferation; this effect occurred even in ATC cells that were unresponsive to RS5444 due to a lack of expression of PPARγ. Our results implicate RhoB as a novel intermediate in critical signaling pathways and as an additional target for therapeutic intervention in ATC. [Cancer Res 2009;69(4):1536–44]
Predicting Relapse in Favorable Histology Wilms Tumor Using Gene Expression Analysis: A Report from the Renal Tumor Committee of the Children's Oncology Group
Authors: Huang Chiang-Ching , Gadd Samantha , Breslow Norman , Cutcliffe Colleen , Sredni Simone T. , Helenowski Irene B. , Dome Jeffrey S. , Grundy Paul E. , Green Daniel M. , Fritsch Michael K. , Perlman Elizabeth J.
Published: February 2009

Purpose: The past two decades has seen significant improvement in the overall survival of patients with favorable histology Wilms tumor (FHWT); however, this progress has reached a plateau. Further improvements may rely on the ability to better stratify patients by risk of relapse. This study determines the feasibility and potential clinical utility of classifiers of relapse based on global gene expression analysis.

Experimental Design: Two hundred fifty FHWT of all stages enriched for relapses treated on National Wilms Tumor Study-5 passed quality variables and were suitable for analysis using oligonucleotide arrays. Relapse risk stratification used support vector machine; 2- and 10-fold cross-validations were applied.

Results: The number of genes associated with relapse was less than that predicted by chance alone for 106 patients (32 relapses) with stages I and II FHWT treated with chemotherapy, and no further analyses were done. This number was greater than expected by chance for 76 local stage III patients. Cross-validation including an additional 68 local stage III patients (total 144 patients, 53 relapses) showed that classifiers for relapse composed of 50 genes were associated with a median sensitivity of 47% and specificity of 70%.

Conclusions: This study shows the feasibility and modest accuracy of stratifying local stage III FHWT using a classifier of <50 genes. Validation using an independent patient population is needed. Analysis of genes differentially expressed in relapse patients revealed apoptosis, Wnt signaling, insulin-like growth factor pathway, and epigenetic modification to be mechanisms important in relapse. Potential therapeutic targets include FRAP/MTOR and CD40.