bluuebunny/crossref_metadata_2025 huggingface dataset:
‘A Miserable Sham’: Flora Annie Steel's Short Fictions and the Question of Indian Women's Reform
Authors: Roy Shampa
Published: March 2010

The article examines a few short stories of Flora Annie Steel, a Scottish memsahib who spent a number of decades in the late nineteenth century in India with her husband, a British colonial official. Steel's short stories are interesting because they were produced at a time when most Anglo-Indian fictions (especially those authored by memsahibs) focused exclusively on station romances, and they explore with some seriousness and sense of complexity, issues related to the impact of Imperial reformatory intervention in the lives of Indian women. Her female contemporaries wrote fictions that more often than not completely ignored the existence of Indians, and even famous male writers like Kipling stereotypically reduced Indian women either to sexually licentious or completely passive, voiceless entities. Steel, in her stories, examines questions of gender, sexuality and reform in the context of Indian women's lives in ways that often seem to go beyond such racial stereotypes. The stories have been examined within the context of the different political and social formations of the specific regions – Punjab or Bengal – in which they are based, since women's reform had very different trajectories in these regions. The remarkableness of Steel's stories, however, lies in their attempting to look at the reform question from the Indian women's perspectives. What cannot be ignored are the ways in which these stories attempt to go beyond the prevalent Anglo-Indian modes of stereotyping or completely erasing Indian women and register their voices in examining questions related to their reform. This is not to say that racial and Imperial hierarchies are entirely abandoned in her writings. In fact the omniscient narrator in these fictions often narrates in ways that sustain and strengthen such hierarchies. However, there are moments when the diegetic narrative mode gives way to an ironically nuanced narrative voice and to ambivalences that seem to gesture at complex questioning of the bases of Imperial authority and its ostensibly benevolent intervention in the lives of Indian women. It is these moments that make the stories worth exploring.
The Gift of Gametes – Unconscious Motivation, Commodification and Problematics of Genealogy
Authors: Raphael-Leff Joan
Published: March 2010

Three-way baby making is not new: genetic surrogacy existed in Biblical times and donor insemination was recorded in Britain over 200 years ago. However, the gift of gametes between women breaks all social conventions. This paper examines the phenomenon of gamete-donation questioning whether a ‘gift’ of such magnitude can ever be ‘free’ (as the Human Fertilisation & Embryology Authority advocates), or a ‘true’ gift (in Derridian terms). Exploration of this unprecedented ‘gift’ from a psychoanalytic approach is supplemented by an interdisciplinary one, drawing on the gift literature in philosophy, anthropology, ethnography and socioeconomics, as well as neonatal research and reproductive medicine. Critics note the dearth of analyses that take seriously the psychological ramifications of contemporary treatments, protocols and expectations in reproductive medicine. Based on psychoanalytic therapy within a clinical practice devoted to reproductive issues, the author argues that institutionalised asexual reproduction alters unconscious conceptualisations of the act of procreation – converting the passionate intimacy of primal scene into a clinical coupling of gametes in a mechanised arena. The author argues that, too charged to contemplate, the gamete's transcendent quality and blurring of elementary personae/ res distinctions leads protagonists, including professionals, to defensive commodification. Multiple emotional meanings are ascribed to gifted gametes by each in the triangle of donor, recipient and offspring, illustrated here with verbatim material. This article addresses some of the far-reaching socio-political consequences for class, race, age, gender and sexuality of asexual reproduction, related to selection procedures and uneven global and local distribution of fertility treatment and its cost in financial, physical, practical and emotional terms. Similarly, feminist unease over (patriarchal) reproductive control and gatekeeping policies are considered, as well as ethical concerns over genetic manipulation, pre-implantation screening, sex selection, selective foetocide and potential exploitation of transnational donors and surrogates.
Effects of sintering temperature on microstructure and high field strain of niobium-strontium doped morphotropic lead zirconate titanate
Authors: Kungl Hans , Hoffmann Michael J.
Published: March 2010

Electric field induced strain is one of the most important performance parameters for multilayer ferroelectric actuators. In these devices, donor doped morphotropic lead zirconate titanate (PZT) ceramics are the materials currently used. Strain and, more general, electromechanical properties of these piezoceramics are grain size dependent. Any attempts to decrease the sintering temperature will suffer from the drawback, that changing Ts will also change the grain size and therefore the electromechanical properties. A series of NbSr-doped PZT materials with 11 different Zr/Ti ratios over the whole range of the morphotropic phase boundary has been prepared, and sintered at temperatures between 975 and 1100 °C. Grain size and x-ray diffraction patterns were evaluated and the strain behavior was measured and analyzed. Qualitative similar effects of grain size on strain behavior were found for all morphotropic PZT 1Nb2Sr compositions: When lowering the sintering temperature, field induced strain decreases whereas the remanent strain increases. Quantitative differences between the materials indicate that, in addition to the influence from the grain size, there are effects specific for the compositions, which are most probably related to changes in phase composition. From the inverse behavior of remanent strain and field induced strain versus grain size, on a macroscopic level, a description of the mechanisms which govern the effects of grain size on strain is derived.
Mean field representation of the natural and actuated cylinder wake
Authors: Tadmor Gilead , Lehmann Oliver , Noack Bernd R. , Morzyński Marek
Published: March 2010

The necessity to include dynamic mean field representations in low order Galerkin models, and the role and form of such representations, are explored along natural and forced transients of the cylinder wake flow. The shift mode was introduced by Noack et al. [J. Fluid Mech. 497, 335 (2003)] as a least-order Galerkin representation of mean flow variations. The need to include the shift mode was argued in that paper in terms of the dynamic properties of a low order Galerkin model. The present study revisits and elucidates this issue with a direct focus on the Navier–Stokes equations (NSEs) and on the bilateral coupling between variations in the fluctuation growth rate and mean flow variations in the NSE. A detailed transient modal energy flow analysis is introduced as a new tool to quantitatively demonstrate the indispensable role of mean field variations, as well as the capacity of the shift mode to represent that contribution. Four variants of local and global shift mode derivations are examined and compared, including the geometric approach of Noack et al. and shift modes derived by a direct appeal to the NSE. Combined with the conclusions of the energy flow analysis, the similarity of the resulting shift modes indicates that the shift mode is no accident: indeed it is an intrinsic component of transient dynamics. Mean field representations can be found as implicit components in successful low order Galerkin models. We therefore argue for the benefit of the simple and robust explicit formulation in terms of added shift modes.
Experimental basis for laser-plasma interactions in ignition hohlraums at the National Ignition Facility
Authors: Froula D. H. , Divol L. , London R. A. , Berger R. L. , Döppner T. , Meezan N. B. , Ralph J. , Ross J. S. , Suter L. J. , Glenzer S. H.
Published: March 2010

A series of laser-plasma interaction experiments is presented using gas-filled hohlraums that shed light on the behavior of stimulated Raman scattering and stimulated Brillouin scattering at various plasma conditions encountered in indirect drive ignition designs. Detailed experimental results are presented that quantify the density, temperature, and intensity thresholds for both of these instabilities. In addition to controlling plasma parameters, the National Ignition Campaign relies on optical beam smoothing techniques to mitigate backscatter and the results presented show that polarization smoothing is effective at controlling backscatter. These results provide an experimental basis for the forthcoming experiments on National Ignition Facility.
Measurement of extraction and absorption parameters in GaN-based photonic-crystal light-emitting diodes
Authors: Matioli Elison , Fleury Blaise , Rangel Elizabeth , Hu Evelyn , Speck James , Weisbuch Claude
Published: March 2010

The light extraction efficiency of photonic-crystal (PhC) light-emitting diodes (LEDs) relies on the competition between the PhC extraction and dissipation mechanisms of the guided light within the LED. This work presents the experimental determination of the PhC extraction length of each guided mode and the absorption coefficient of the active region (AR) and quantum wells (QWs) from the observation of the LED far-field emission using a high-resolution angle-spectrum-resolved measurement. The angular and spectral linewidths of the extracted guided modes reveal, depending on the spectral range, the modal extraction length of the PhCs, the AR absorption length, or a combination of both. Modes with a high confinement with the QWs presented a shorter absorption length compared with their extraction length by a shallow surface PhC (95-nm-deep), meaning that the AR absorption was a more efficient mechanism than the PhC extraction. The measured modal extraction length of the shallow surface PhC varied in the range of 55–120 μm, which determines the minimum dimensions of the device and the maximum acceptable dissipation length for an efficient extraction of the guided light by the PhCs. This paper presents also a discussion on the PhC designs that yield PhC extraction lengths shorter than other dissipation lengths, a fundamental requirement for high-efficiency PhC LEDs. The same technique was also applied to estimate the absorption coefficient of the InGaN-based QWs, and can be extended to experimentally determine losses by metallic layers from electrical contacts or other dissipation mechanisms, which are parameters of interest to a broader class of optoelectronic devices, not only PhC LEDs.
NIMROD: The Near and InterMediate Range Order Diffractometer of the ISIS second target station
Authors: Bowron D. T. , Soper A. K. , Jones K. , Ansell S. , Birch S. , Norris J. , Perrott L. , Riedel D. , Rhodes N. J. , Wakefield S. R. , Botti A. , Ricci M.-A. , Grazzi F. , Zoppi M.
Published: March 2010

NIMROD is the Near and InterMediate Range Order Diffractometer of the ISIS second target station. Its design is optimized for structural studies of disordered materials and liquids on a continuous length scale that extends from the atomic, upward of 30 nm, while maintaining subatomic distance resolution. This capability is achieved by matching a low and wider angle array of high efficiency neutron scintillation detectors to the broad band-pass radiation delivered by a hybrid liquid water and liquid hydrogen neutron moderator assembly. The capabilities of the instrument bridge the gap between conventional small angle neutron scattering and wide angle diffraction through the use of a common calibration procedure for the entire length scale. This allows the instrument to obtain information on nanoscale systems and processes that are quantitatively linked to the local atomic and molecular order of the materials under investigation.
Modeling the basin of attraction as a two-dimensional manifold from experimental data: Applications to balance in humans
Authors: Zakynthinaki Maria S. , Stirling James R. , Cordente Martínez Carlos A. , Díaz de Durana Alfonso López , Quintana Manuel Sillero , Romo Gabriel Rodríguez , Molinuevo Javier Sampedro
Published: March 2010

We present a method of modeling the basin of attraction as a three-dimensional function describing a two-dimensional manifold on which the dynamics of the system evolves from experimental time series data. Our method is based on the density of the data set and uses numerical optimization and data modeling tools. We also show how to obtain analytic curves that describe both the contours and the boundary of the basin. Our method is applied to the problem of regaining balance after perturbation from quiet vertical stance using data of an elite athlete. Our method goes beyond the statistical description of the experimental data, providing a function that describes the shape of the basin of attraction. To test its robustness, our method has also been applied to two different data sets of a second subject and no significant differences were found between the contours of the calculated basin of attraction for the different data sets. The proposed method has many uses in a wide variety of areas, not just human balance for which there are many applications in medicine, rehabilitation, and sport.
Note: Design and test of a compact flexure z-stage for atomic force microscopy
Authors: Bracco Gianangelo , Gussoni Antonio , Pagnini Luisa Carlotta
Published: March 2010

We describe the design and test of a flexure z-stage with 12.5 mm height and 4 μm travel to be coupled with a commercial xy stage. The geometrical model was simulated by means of finite element calculations which have provided an accurate description of the stage dynamics also taking into account the effect of a load to get a resonance frequency of 8 kHz with a 10 g load. The tests of the complete xyz stage were performed in intermittent-contact mode on a sample having periodic features (1.6 μm period, 100 nm height) and with additional loads to increase the mass up to 20 g. The results show that for a 10 g load the surface profiles are well reproduced up to 60 μm/s while with a 20 g sample the speed is reduced to 40 μm/s.
Sensitivity of predicted gas hydrate occupancies on treatment of intermolecular interactions
Authors: Thomas Caroline , Picaud Sylvain , Ballenegger Vincent , Mousis Olivier
Published: March 2010

The sensitivity of gas hydrate occupancies predicted on the basis of van der Waals–Platteeuw theory is investigated, as a function of the intermolecular guest-water interaction potential model, and of the number of water molecules taken into account. Simple analytical correction terms that account for the interactions with the water molecules beyond the cutoff distance are introduced, and shown to improve significantly the convergence rate, and hence the efficiency of the computation of the Langmuir constants. The predicted cage occupancies in pure methane and pure carbon dioxide clathrates, calculated using different recent guest-water pair potentials models derived from ab initio calculations, can vary significantly depending on the model. That sensitivity becomes especially strong in the case of multiple guest clathrates. It is shown that the abundances of coenclathrated molecules in multiple guest clathrate hydrates potentially formed on the surface of Mars can vary by more than two orders of magnitude depending on the model. These results underline the strong need for experimental data on pure and multiple guest clathrate hydrates, in particular in the temperature and pressure range that are relevant in extreme environment conditions, to discriminate among the theoretical models.
Directional and controllable edge-emitting ZnO ultraviolet random laser diodes
Authors: Liang H. K. , Yu S. F. , Yang H. Y.
Published: March 2010

Room-temperature ultraviolet random lasing action is demonstrated from a p-GaN/annealed i-ZnO:Al(3%)/n-ZnO:Al(5%) buried heterojunction diode with a 2 μm rib waveguide. Excellent electrical-to-optical conversion efficiency is achieved by strong electrical and optical confinement of a buried heterojunction rib waveguide structure. Hence, emission intensity (threshold current) can be enhanced (reduced) by ∼9 times (∼40%). Directional emission as well as controllability on the number of the random lasing modes can also be achieved.
Nanogap quantum dot photodetectors with high sensitivity and bandwidth
Authors: Hegg Michael C. , Horning Matthew P. , Baehr-Jones Tom , Hochberg Michael , Lin Lih Y.
Published: March 2010

We report high-performance nanoscale photodetectors utilizing annealed nanocrystal quantum dots (QDs) within a nanoscale metal electrode gap. By optimizing the nanogap size and fabrication process, the device demonstrates a significantly better sensitivity (noise equivalent power=7.76×10−14 W/Hz1/2) and bandwidth (≥125 kHz) than previously reported nanoscale photodetectors. Furthermore, by utilizing a lateral photoconduction structure and a self-assembled layer of QDs, the detector fabrication is highly compatible with many substrates and device architectures.
Carrier velocity in InAlN/AlN/GaN heterostructure field effect transistors on Fe-doped bulk GaN substrates
Authors: Leach J. H. , Wu M. , Ni X. , Li X. , Xie J. , Özgür Ü. , Morkoç H. , Paskova T. , Preble E. , Evans K. R. , Lu Chang-Zhi
Published: March 2010

We report microwave characteristics of field effect transistors employing InAlN/AlN/GaN heterostructures grown on low-defect-density bulk Fe-doped GaN substrates. We achieved unity current gain cutoff frequencies of 14.3 and 23.7 GHz for devices with gate lengths of 1 and 0.65 μm, respectively. Measurements as a function of applied bias allow us to estimate the average carrier velocity in the channel to be ∼1.0×107 cm/sec for a 1 μm device. Additionally, we found nearly no gate lag in the devices, which is considered a precondition for good performance under large signal operation.
Evaluation of heat current formulations for equilibrium molecular dynamics calculations of thermal conductivity
Authors: Guajardo-Cuéllar Alejandro , Go David B. , Sen Mihir
Published: March 2010

Equilibrium molecular dynamics combined with the Green–Kubo formula can be used to calculate the thermal conductivity of materials such as germanium and carbon. The foundation of this calculation is extracting the heat current from the results and implementing it into the Green–Kubo formula. This work considers all formulations from the literature that calculate the heat current for the Tersoff potential, the interatomic potential most applicable to semiconductor materials. The formulations for the heat current are described, and results for germanium and carbon are presented. The formulations are compared with respect to how well they capture the physics of the Tersoff potential and how well the calculated value of the thermal conductivity reflects the experimentally measured value.
Low temperature germanium to silicon direct wafer bonding using free radical exposure
Authors: Byun Ki Yeol , Ferain Isabelle , Fleming Pete , Morris Michael , Goorsky Mark , Colinge Cindy
Published: March 2010

A low temperature germanium (Ge) to silicon (Si) wafer bonding method was demonstrated by in situ radical activation bonding in vacuum. In order to gain further insight into the bonding mechanism, the Ge surface chemistry after either oxygen or nitrogen radical activation was analyzed by means of angle-resolved x-ray photoelectron spectroscopy. After low temperature direct bonding of Ge to Si followed by annealing at 200 and 300 °C, advanced imaging techniques were used to characterize the bonded interface.
Vertical electric field tuning of the exciton fine structure splitting and photon correlation measurements of GaAs quantum dot
Authors: Marcet S. , Ohtani K. , Ohno H.
Published: March 2010

The effects of a vertical electric field on the fine structure splitting of neutral exciton of monolayer fluctuation GaAs quantum dots were investigated. Using the gate voltage between the top gate electrode and the bottom n-GaAs substrate, the fine structure splitting of the neutral exciton was tuned to 15–30 μeV. Photon correlation measurements demonstrate neutral exciton single photon emission and neutral exciton—biexciton cascaded emission.
Low defect-mediated reverse-bias leakage in (0001) GaN via high-temperature molecular beam epitaxy
Authors: Law J. J. M. , Yu E. T. , Koblmüller G. , Wu F. , Speck J. S.
Published: March 2010

Conductive atomic force microscopy, scanning electron microscopy, and x-ray diffraction were used to determine the effects of Ga/N flux ratio on the conductivity of current leakage paths in GaN grown by molecular beam epitaxy. Our data reveal a band of fluxes near Ga/N≈1 for which these pathways ceased to be observable. We conclude that changes in surface defects surrounding or impurities along screw-component threading dislocations are responsible for their conductive nature. These observations suggest a method for controlling the primary source of reverse-bias Schottky contact leakage in n-type GaN grown by molecular beam epitaxy.
Bone marrow stromal cells use TGF-β to suppress allergic responses in a mouse model of ragweed-induced asthma
Authors: Nemeth Krisztian , Keane-Myers Andrea , Brown Jared M. , Metcalfe Dean D. , Gorham James D. , Bundoc Virgilio G. , Hodges Marcus G. , Jelinek Ivett , Madala Satish , Karpati Sarolta , Mezey Eva
Published: March 2010

Bone marrow stromal cells [BMSCs; also known as mesenchymal stem cells (MSCs)] effectively suppress inflammatory responses in acute graft-versus-host disease in humans and in a number of disease models in mice. Many of the studies concluded that BMSC-driven immunomodulation is mediated by the suppression of proinflammatory Th1 responses while rebalancing the Th1/Th2 ratio toward Th2. In this study, using a ragweed induced mouse asthma model, we studied if BMSCs could be beneficial in an allergic, Th2-dominant environment. When BMSCs were injected i.v. at the time of the antigen challenge, they protected the animals from the majority of asthma-specific pathological changes, including inhibition of eosinophil infiltration and excess mucus production in the lung, decreased levels of Th2 cytokines (IL-4, IL-5, and IL-13) in bronchial lavage, and lowered serum levels of Th2 immunoglobulins (IgG1 and IgE). To explore the mechanism of the effect we used BMSCs isolated from a variety of knockout mice, performed in vivo blocking of cytokines and studied the effect of asthmatic serum and bronchoalveolar lavage from ragweed challenged animals on the BMSCs in vitro. Our results suggest that IL-4 and/or IL-13 activate the STAT6 pathway in the BMSCs resulting in an increase of their TGF-β production, which seems to mediate the beneficial effect, either alone, or together with regulatory T cells, some of which might be recruited by the BMSCs. These data suggest that, in addition to focusing on graft-versus-host disease and autoimmune diseases, allergic conditions—specifically therapy resistant asthma—might also be a likely target of the recently discovered cellular therapy approach using BMSCs.
Rye Flour Extraction Rate Affects Maillard Reaction Development, Antioxidant Activity, and Acrylamide Formation in Bread Crisps
Authors: Capuano Edoardo , Garofalo Giovanna , Napolitano Aurora , Zielinski Henryk , Fogliano Vincenzo
Published: March 2010

This report shows the effect of rye flour extraction rate on Maillard reaction, antioxidant activity, and acrylamide formation during toasting of rye bread crisps. Four rye flours with extraction rates of 70, 85, 95, and 100% were tested. Maillard reaction development was studied by measuring browning development, hydroxymethylfurfural (HMF), and glucosilisomaltol (GIM) formation, as well as antioxidant activity. Results showed that HMF and GIM concentrations in toasted bread crisps were higher as the flour extraction rate increases. Antioxidant activity increased during toasting as a consequence of antioxidant Maillard reaction product formation. Acrylamide concentration was clearly affected by free asparagine content of flour, while no effect of dietary fiber and natural antioxidant content of flours had an effect on acrylamide formation. Overall data suggest that the rate of Maillard reaction is higher in whole flours because of their higher free amino acid and protein content.
CDK-dependent complex formation between replication proteins Dpb11, Sld2, Pol ɛ, and GINS in budding yeast
Authors: Muramatsu Sachiko , Hirai Kazuyuki , Tak Yon-Soo , Kamimura Yoichiro , Araki Hiroyuki
Published: March 2010

Eukaryotic chromosomal DNA replication requires cyclin-dependent kinase (CDK) activity. CDK phosphorylates two yeast replication proteins, Sld3 and Sld2, both of which bind to Dpb11 when phosphorylated. These phosphorylation-dependent interactions are essential and are the minimal requirements for CDK-dependent activation of DNA replication. However, how these interactions activate DNA replication has not been elucidated. Here, we show that CDK promotes the formation of a newly identified fragile complex, the preloading complex (pre-LC) containing DNA polymerase ɛ (Pol ɛ), GINS, Sld2, and Dpb11. Formation of the pre-LC requires phosphorylation of Sld2 by CDK, but is independent of DNA replication, protein association with replication origins, and Dbf4-dependent Cdc7 kinase, which is also essential for the activation of DNA replication. We also demonstrate that Pol ɛ, GINS, Dpb11, and CDK-phosphorylated Sld2 form a complex in vitro. The genetic interactions between Pol ɛ, GINS, Sld2, and Dpb11 suggest further that they form an essential complex in cells. We propose that CDK regulates the initiation of DNA replication in budding yeast through formation of the pre-LC.
Dynamic alteration of protein expression profiles during neoplastic transformation of rat hepatic oval‐like cells
Authors: Li Xuefei , Li Yan , Kang Xiaonan , Guo Kun , Li Haiyu , Gao Dongmei , Sun Lu , Liu Yinkun
Published: March 2010

To explore the molecular basis of neoplastic transformation of hepatic oval cells, a proteomic strategy was utilized to examine the global protein expression alterations during neoplastic transformation of rat hepatic oval‐like cells. N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG)‐initiated WB‐F344 cells were treated with H2O2 for neoplastic transformation. The transformed cells were identified by soft agar assay and MTT assay. The subsequent proteomic separation and identification were performed with 2‐DE followed by MALDI‐TOF‐MS/MS analysis. Of the 148 differentially displayed protein spots analyzed, 121 spots representing 79 distinct proteins were finally identified. The expression levels of interested proteins were validated by western blotting including 40 S ribosomal protein A (RPSA) and cytokeratin 8. Bioinformatics annotations indicated that these identified proteins were enriched with oxidoreduction and stress response; transcription, translation, and protein processing; and energy/metabolism functions. Interestingly, 17 of the identified proteins were also found to be involved in early hepatic differentiation of mouse embryonic stem (ES) cells in our previous study. Twenty‐six proteins had been reported as being dysregulated in hepatocellular carcinoma and other cancers. It suggested that these changed proteins may be implicated in neoplastic transformation of WB‐F344 cells. The results may provide some clues for understanding the molecular mechanisms of hepatocarcinogenesis as viewed from dysregulation of differentiation.

(Cancer Sci 2010; 101: 1099–1107)
Bortezomib potentially inhibits cellular growth of vascular endothelial cells through suppression of G2/M transition
Authors: Tamura Daisuke , Arao Tokuzo , Tanaka Kaoru , Kaneda Hiroyasu , Matsumoto Kazuko , Kudo Kanae , Aomatsu Keiichi , Fujita Yoshihiko , Watanabe Takashi , Saijo Nagahiro , Kotani Yoshikazu , Nishimura Yoshihiro , Nishio Kazuto
Published: March 2010

Bortezomib, a selective 26S proteasome inhibitor, has shown clinical benefits against refractory multiple myeloma. The indirect anti‐angiogenic activity of bortezomib has been widely recognized; however, the growth‐inhibitory mechanism of bortezomib on vascular endothelial cells remains unclear, especially on the cell cycle. Here, we showed that bortezomib (2 nM of the IC50 value) potently inhibited the cellular growth of human umbilical vascular endothelial cells (HUVECs) via a vascular endothelial growth factor receptor (VEGFR)‐independent mechanism resulting in the induction of apoptosis. Bortezomib significantly increased the vascular permeability of HUVECs, whereas a VEGFR‐2 tyrosine kinase inhibitor decreased it. Interestingly, a cell cycle analysis using flow cytometry, the immunostaining of phospho‐histone H3, and Giemsa staining revealed that bortezomib suppressed the G2/M transition of HUVECs, whereas the mitotic inhibitor paclitaxel induced M‐phase accumulation. A further analysis of cell cycle‐related proteins revealed that bortezomib increased the expression levels of cyclin B1, the cdc2/cyclin B complex, and the phosphorylation of all T14, Y15, and T161 residues on cdc2. Bortezomib also increased the ubiquitination of cyclin B1 and wee1, but inhibited the kinase activity of the cdc2/cyclin B complex. These protein modifications support the concept that bortezomib suppresses the G2/M transition, rather than causing M‐phase arrest. In conclusion, we demonstrated that bortezomib potently inhibits cell growth by suppressing the G2/M transition, modifying G2/M‐phase‐related cycle regulators, and increasing the vascular permeability of vascular endothelial cells. Our findings reveal a cell cycle‐related mode of action and strongly suggest that bortezomib exerts an additional unique vascular disrupting effect as a vascular targeting drug. (Cancer Sci 2010)
Epigenetic aberrations and therapeutic implications in gliomas
Authors: Natsume Atsushi , Kondo Yutaka , Ito Motokazu , Motomura Kazuya , Wakabayashi Toshihiko , Yoshida Jun
Published: March 2010

Almost all cancer cells have multiple epigenetic abnormalities, which combine with genetic changes to affect many cellular processes, including cell proliferation and invasion, by silencing tumor‐suppressor genes. In this review, we focus on the epigenetic mechanisms of DNA hypomethylation and CpG island hypermethylation in gliomas. Aberrant hypermethylation in promoter CpG islands has been recognized as a key mechanism involved in the silencing of cancer‐associated genes and occurs at genes with diverse functions related to tumorigenesis and tumor progression. Such promoter hypermethylation can modulate the sensitivity of glioblastomas to drugs and radiotherapy. As an example, the methylation of the O6‐methylguanine DNA methyltransferase (MGMT) promoter is a specific predictive biomarker of tumor responsiveness to chemotherapy with alkylating agents. Further, we reviewed reports on pyrosequencing – a simple technique for the accurate and quantitative analysis of DNA methylation. We believe that the quantification of MGMT methylation by pyrosequencing might enable the selection of patients who are most likely to benefit from chemotherapy. Finally, we also evaluated the potential of de novo NY‐ESO‐1, the most immunogenic cancer/testis antigen (CTA) discovered thus far, as an immunotherapy target. The use of potent epigenetics‐based therapy for cancer cells might restore the abnormally regulated epigenomes to a more normal state through epigenetic reprogramming. Thus, epigenetic therapy may be a promising and potent treatment for human neoplasia. (Cancer Sci 2010)
Non‐thermal cytocidal effect of infrared irradiation on cultured cancer cells using specialized device
Authors: Tanaka Yohei , Matsuo Kiyoshi , Yuzuriha Shunsuke , Yan Huimin , Nakayama Jun
Published: March 2010

As infrared penetrates the skin, thermal effects of infrared irradiation on cancer cells have been investigated in the field of hyperthermia. We evaluated non‐thermal effects of infrared irradiation using a specialized device (1100–18000 nm with filtering of wavelengths between 1400 and 1500 nm and contact cooling) on cancer cells. In in vitro study, five kinds of cultured cancer cell lines (MCF7 breast cancer, HeLa uterine cervical cancer, NUGC‐4 gastric cancer, B16F0 melanoma, and MDA‐MB435 melanoma) were irradiated using the infrared device, and then the cell proliferation activity was evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium (MTS) assay. Proliferation of all the cancer cell lines was significantly suppressed by infrared irradiation. Total infrared output appeared to be correlated with cell survival. Increased temperature during infrared irradiation appeared not to play a role in cell survival. The maximum temperature elevation in the wells after each shot in the 20 and 40 J/cm2 culture was 3.8°C and 6.9°C, respectively. In addition, we have shown that infrared irradiation significantly inhibited the tumor growth of MCF7 breast cancer transplanted in severe combined immunodeficiency mice and MDA‐MB435 melanoma transplanted in nude mice in vivo. Significant differences between control and irradiated groups were observed in tumor volume and frequencies of TUNEL‐positive and Ki‐67‐positive cells. These results indicate that infrared, independent of thermal energy, can induce cell killing of cancer cells. As this infrared irradiation schedule reduces discomfort and side effects, reaches the deep subcutaneous tissues, and facilitates repeated irradiations, it may have potential as an application for treating various forms of cancer. (Cancer Sci 2010)
The relation between different dimensions of alcohol consumption and burden of disease: an overview
Authors: Rehm Jürgen , Baliunas Dolly , Borges Guilherme L. G. , Graham Kathryn , Irving Hyacinth , Kehoe Tara , Parry Charles D. , Patra Jayadeep , Popova Svetlana , Poznyak Vladimir , Roerecke Michael , Room Robin , Samokhvalov Andriy V. , Taylor Benjamin
Published: March 2010

Aims As part of a larger study to estimate the global burden of disease and injury attributable to alcohol: to evaluate the evidence for a causal impact of average volume of alcohol consumption and pattern of drinking on diseases and injuries; to quantify relationships identified as causal based on published meta‐analyses; to separate the impact on mortality versus morbidity where possible; and to assess the impact of the quality of alcohol on burden of disease.

Methods Systematic literature reviews were used to identify alcohol‐related diseases, birth complications and injuries using standard epidemiological criteria to determine causality. The extent of the risk relations was taken from meta‐analyses.

Results Evidence of a causal impact of average volume of alcohol consumption was found for the following major diseases: tuberculosis, mouth, nasopharynx, other pharynx and oropharynx cancer, oesophageal cancer, colon and rectum cancer, liver cancer, female breast cancer, diabetes mellitus, alcohol use disorders, unipolar depressive disorders, epilepsy, hypertensive heart disease, ischaemic heart disease (IHD), ischaemic and haemorrhagic stroke, conduction disorders and other dysrhythmias, lower respiratory infections (pneumonia), cirrhosis of the liver, preterm birth complications and fetal alcohol syndrome. Dose–response relationships could be quantified for all disease categories except for depressive disorders, with the relative risk increasing with increased level of alcohol consumption for most diseases. Both average volume and drinking pattern were linked causally to IHD, fetal alcohol syndrome and unintentional and intentional injuries. For IHD, ischaemic stroke and diabetes mellitus beneficial effects were observed for patterns of light to moderate drinking without heavy drinking occasions (as defined by 60+ g pure alcohol per day). For several disease and injury categories, the effects were stronger on mortality compared to morbidity. There was insufficient evidence to establish whether quality of alcohol had a major impact on disease burden.

Conclusions Overall, these findings indicate that alcohol impacts many disease outcomes causally, both chronic and acute, and injuries. In addition, a pattern of heavy episodic drinking increases risk for some disease and all injury outcomes. Future studies need to address a number of methodological issues, especially the differential role of average volume versus drinking pattern, in order to obtain more accurate risk estimates and to understand more clearly the nature of alcohol–disease relationships.
Preclinical anti‐myeloma activity of the novel HDAC‐inhibitor JNJ‐26481585
Authors: Stühmer Thorsten , Arts Janine , Chatterjee Manik , Borawski Johanna , Wolff André , King Peter , Einsele Hermann , Leo Eugen , Bargou Ralf C.
Published: March 2010

Pharmacological inhibitors of histone deacetylases (HDACs) are currently being developed and tested as anti‐cancer agents and may be useful to enhance the therapeutic efficiency of established anti‐myeloma treatments. This study preclinically evaluated the effects of the ‘second generation’ pan‐HDAC inhibitor JNJ‐26481585 on human multiple myeloma (MM) cells from established cell lines and primary MM samples (n = 42). Molecular responses in both groups of MM cells included histone acetylation, a shift in Bcl2‐family members towards proapoptotic bias, attenuation of growth and survival pathway activity and Hsp72 induction. Mcl‐1 depletion and Hsp72 induction were the most reliable features observed in JNJ‐26481585‐treated primary MM samples. The drug alone effectively induced myeloma cell death at low nanomolar concentrations. In vitro combination of JNJ‐26481585 with anti‐myeloma therapeutic agents generally resulted In effects close to additivity. In view of the favourable activity of this novel HDAC‐inhibitor towards primary myeloma cells further evaluation in a clinical setting is warranted.
Functional diversity measures: an overview of their redundancy and their ability to discriminate community assembly rules
Authors: Mouchet Maud A. , Villéger Sébastien , Mason Norman W. H. , Mouillot David
Published: March 2010

1. Indices quantifying the functional aspect of biodiversity are essential in understanding relationships between biodiversity, ecosystem functioning and environmental constraints. Many indices of functional diversity have been published but we lack consensus about what indices quantify, how redundant they are and which ones are recommended.

2. This study aims to build a typology of functional diversity indices from artificial data sets encompassing various community structures (different assembly rules, various species richness levels) and to identify a set of independent indices able to discriminate community assembly rules.

3. Our results confirm that indices can be divided into three main categories, each of these corresponding to one aspect of functional diversity: functional richness, functional evenness and functional divergence. Most published indices are highly correlated and quantify functional richness while quadratic entropy (Q) represents a mix between functional richness and functional divergence. Conversely, two indices (FEve and FDiv respectively quantifying functional evenness and functional divergence) are rather independent to all the others. The power analysis revealed that some indices efficiently detect assembly rules while others performed poorly.

4. To accurately assess functional diversity and establish its relationships with ecosystem functioning and environmental constraints, we recommend investigating each functional component separately with the appropriate index. Guidelines are provided to help choosing appropriate indices given the issue being investigated.

5. This study demonstrates that functional diversity indices have the potential to reveal the processes that structure biological communities. Combined with complementary methods (phylogenetic and taxonomic diversity), the multifaceted framework of functional diversity will help improve our understanding of how biodiversity interacts with ecosystem processes and environmental constraints.
A hitchhiker’s guide to a crowded syconium: how do fig nematodes find the right ride?
Authors: Krishnan Anusha , Muralidharan Subhashini , Sharma Likhesh , Borges Renee M.
Published: March 2010

1. Organisms with low mobility, living within ephemeral environments, need to find vehicles that can disperse them reliably to new environments. The requirement for specificity in this passenger–vehicle relationship is enhanced within a tritrophic interaction when the environment of passenger and vehicle is provided by a third organism. Such relationships pose many interesting questions about specificity within a tritrophic framework.

2. Central to understanding how these tritrophic systems have evolved, is knowing how they function now. Determining the proximal cues and sensory modalities used by passengers to find vehicles and to discriminate between reliable and non‐reliable vehicles is, therefore, essential to this investigation.

3. The ancient, co‐evolved and highly species‐specific nursery pollination mutualism between figs and fig wasps is host to species‐specific plant‐parasitic nematodes which use fig wasps to travel between figs. Since individual globular fig inflorescences, i.e. syconia, serve as incubators for hundreds of developing pollinating and parasitic wasps, a dispersal‐stage nematode within such a chemically complex and physically crowded environment is faced with the dilemma of choosing the right vehicle for dispersal into a new fig. Such a system therefore affords excellent opportunities to investigate mechanisms that contribute to the evolution of specificity between the passenger and the vehicle.

4. In this study of fig–wasp–nematode tritrophic interactions in Ficus racemosa within which seven wasp species can breed, we demonstrate using two‐choice as well as cafeteria assays that plant‐parasitic nematodes (Schistonchus racemosa) do not hitch rides randomly on available eclosing wasps within the fig syconium, but are specifically attracted, at close range, i.e. 3 mm distance, to only that vehicle which can quickly, within a few hours, reliably transfer it to another fig. This vehicle is the female pollinating wasp. Male wasps and female parasitic wasps are inappropriate vehicles since the former are wingless and die within the fig, while the latter never enter another fig. Nematodes distinguished between female pollinating wasps and other female parasitic wasps using volatiles and cuticular hydrocarbons. Nematodes could not distinguish between cuticular hydrocarbons of male and female pollinators but used other cues, such as volatiles, at close range, to find female pollinating wasps with which they have probably had a long history of chemical adaptation.

5. This study opens up new questions and hypotheses about the evolution and maintenance of specificity in fig–wasp–nematode tritrophic interactions.
Rethinking the value of high wood density
Authors: Larjavaara Markku , Muller‐Landau Helene C.
Published: March 2010

1. Current thinking holds that wood density mediates a tradeoff between strength and economy of construction, with higher wood density providing higher strength but at higher cost.

2. Yet the further away wood fibres are from the central axis of the trunk, the more they increase the strength of the trunk; thus, a fat trunk of low‐density wood can achieve greater strength at lower construction cost than a thin trunk of high‐density wood.

3. What then are the countervailing advantages of high wood density?

4. We hypothesize that high wood density is associated with lower maintenance costs due to lower trunk surface area, as surface area correlates with maintenance respiration.

5. This advantage would be particularly important to long‐lived trees and could in part explain why they tend to have high wood density.

6. High wood density has also been associated with lower risk of trunk breakage, xylem implosion and pathogen invasion, but we argue that these relationships are not causal and instead reflect correlated selection on other traits of value to long‐lived trees.

7. This revaluation of the costs and benefits of high wood density has important implications for understanding tree life‐history evolution, functional diversity, forest carbon stocks and the impacts of global change.
Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats
Authors: Jacobsen P. R. , Christiansen S. , Boberg J. , Nellemann C. , Hass U.
Published: March 2010

Risk assessment is currently based on the no observed adverse effect levels (NOAELs) for single compounds. Humans are exposed to a mixture of chemicals and recent studies in our laboratory have shown that combined exposure to endocrine disrupters can cause adverse effects on male sexual development, even though the doses of the single compounds are below their individual NOAELs for anti‐androgenic effects. Consequently, we have initiated a large project where the purpose is to study mixture effects of endocrine disrupting pesticides at low doses. In the initial range‐finding mixture studies, rats were gavaged during gestation and lactation with five doses of a mixture of the fungicides procymidone, mancozeb, epoxyconazole, tebuconazole and prochloraz. The mixture ratio was chosen according to the doses of each individual pesticide that produced no observable effects on pregnancy length and pup survival in our laboratory and the dose levels used ranged from 25 to 100% of this mixture. All dose levels caused increased gestation length and dose levels above 25% caused impaired parturition leading to markedly decreased number of live born offspring and high pup perinatal mortality. The sexual differentiation of the pups was affected at 25% and higher as anogenital distance was affected in both male and female offspring at birth and the male offspring exhibited malformations of the genital tubercle, increased nipple retention, and decreased prostate and epididymis weights at pup day 13. The results show that doses of endocrine disrupting pesticides, which appear to induce no effects on gestation length, parturition and pup mortality when judged on their own, induced marked adverse effects on these endpoints in concert with other pesticides. In addition, the sexual differentiation of the offspring was affected. This as well as the predictability of the combination effects based on dose‐additivity modelling will be studied further in a large dose‐response study.
Effects of seed depth and soil aggregates on the emergence of weeds with contrasting seed traits
Authors: GARDARIN A , DÜRR C , COLBACH N
Published: March 2010

GardarinA,DürrC & ColbachN (2010). Effects of seed depth and soil aggregates on the emergence of weeds with contrasting seed traits.Weed Research50, 91–101.

Tillage has a strong impact on weed emergence by burying seeds in the soil and modifying soil structure. Its influence can vary according to seed and seedling characteristics. This article focuses on shoot and radicle elongation in the soil and on seedling mortality caused by soil obstacles. Germinated seeds of nine contrasting weeds were planted in pots and grown in the dark to measure shoot and radicle elongation. Second, the proportion of seedlings blocked under aggregates (20–50 mm) was measured. Shoot growth rate, maximal shoot and radicle lengths were positively correlated with seed mass. Large‐seeded species (e.g.Avena fatua) were more likely to emerge from greater depths (exceeding 20 cm deep). Seedling mortality increased with increasing obstacle size for all species; it was greater for monocotyledonous than for dicotyledonous species and decreased with the shoot diameter. Weed seed depth and soil structure influence emergence of weed species differently, depending on seed mass, shoot diameter and taxa. Including the results of this study in a cropping system‐weed dynamics model would help to predict responses of weeds species to tillage.