bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockade of NFκB activity by Sunitinib increases cell death in Bortezomib‐treated endometrial carcinoma cells
Authors: Sorolla Anabel , Yeramian Andrée , Valls Joan , Dolcet Xavier , Bergadà Laura , Llombart-Cussac Antoni , Martí Rosa Maria , Matias-Guiu Xavier
Published: July 2012

Endometrial carcinoma is one of the most common malignancies in the female genital tract, usually treated by surgery and radiotherapy. Chemotherapy is used when endometrial carcinoma is associated with widespread metastasis or when the tumor recurs after radiation therapy. In the present study, we demonstrate that the tyrosine kinase receptor inhibitor Sunitinib reduces cell viability, proliferation, clonogenicity and induces apoptotic cell death in endometrial carcinoma cell lines, which is not due to its action through the most known targets like VEGFR, nor through EGFR as demonstrated in this work. Interestingly, Sunitinib reduces NFκB transcriptional activity either at basal level or activation by EGF or TNF‐α. We observed that Sunitinib was able to inhibit the Bortezomib‐induced NFκB transcriptional activity which correlates with a decrease of the phosphorylated levels of IKKα and β, p65 and IκBα. We evaluated the nature of the interaction between Sunitinib and Bortezomib by the dose effect method and identified a synergistic effect (combination index < 1). Analogously, silencing of p65 expression by lentiviral‐mediated short‐hairpin RNA delivery in Bortezomib treated cells leads to a strongly increased sensitivity to Bortezomib apoptotic cell death. Altogether our results suggest that the combination of Sunitinib and Bortezomib could be considered a promising treatment for endometrial carcinoma after failure of surgery and radiation.
Boron neutron capture therapy as a novel modality of radiotherapy for oral cancer: Principle and antitumor effect
Authors: Yura Yoshiaki , Fujita Yusei
Published: July 2012

Radiotherapy is essential for the treatment of oral cancer, especially in advanced cases. There has been marked progress in this field due to the prevalence of intensity‐modified radiation therapy and introduction of particle radiotherapy using protons and carbon‐ions. However, these treatments are still non‐selective. Boron neutron capture therapy (BNCT) is a unique modality in which neutron beams destroy only boron compound‐bearing tumor cells while leaving the surrounding normal tissues intact. Thus, BNCT is a selective form of radiotherapy, if high tumor/normal tissue ratio in boron concentration could be achieved. The principle of BNCT, and the basic study of the mechanism by which BNCT exerts antitumor effects using oral squamous cell carcinoma (SCC) cells and oral SCC xenografts in mice are described.
Calcineurin inhibitors and immunosuppression – a tale of two isoforms
Authors: Williams Clintoria R. , Gooch Jennifer L.
Published: July 2012

Organ transplantation is the state of the art for treating end-stage organ failure. Over 25 000 organ transplants are performed in the USA each year. Survival rates following transplantation are now approaching 90% for 1 year and 75% for 5 years. Central to this success was the introduction of drugs that suppress the immune system and prevent rejection. The most commonly used class of immunosuppressing drugs are calcineurin inhibitors (CNIs). Calcineurin is a ubiquitous enzyme that is important for T-cell function. With more people taking CNIs for longer and longer periods of time the consequences of calcineurin inhibition on other organ systems – particularly the kidney – have become a growing concern. Virtually all people who take a CNI will develop some degree of kidney toxicity and up to 10% will progress to kidney failure. In the past 15 years, research into calcineurin action has identified distinct actions of the two main isoforms of the catalytic subunit of the enzyme. The α-isoform is required for kidney function whereas the β-isoform has a predominant role in the immune system. This review will discuss the current state of knowledge about calcineurin isoforms and how these new insights may reshape post-transplant immunosuppression.
The European wintering population of Steller’s Eider Polysticta stelleri reassessed
Authors: AARVAK TOMAS , JOSTEIN ØIEN INGAR , KRASNOV YURI V. , GAVRILO MARIA V. , SHAVYKIN ANATOLY A.
Published: July 2012

Prolonged declines in the number of Steller’s Eider Polysticta stelleri wintering in Europe have raised concerns about the conservation status of the Western Palearctic population. Coordinated helicopter surveys of all known wintering areas in Norway and Russia and ground counts in the Baltic in 2009 found c.27,000 Steller’s Eiders, similar to numbers found during the last such survey in the mid-1990s. However, around 85% of the population now winters in Russia compared to 30–50% then. The reasons for this rapid shift in distribution are unknown but are likely linked to climate change. The continuing small population size, specialist feeding and restricted distribution of Steller’s Eider necessitate continued survey and research to track population changes and provide evidence for conservation management actions to safeguard the species.
The microbiome of the soft palate of swine
Authors: Kernaghan Shaun , Bujold Adina R. , MacInnes Janet I.
Published: July 2012

The tonsil of the soft palate in pigs is a secondary lymphoid tissue that provides a first line of defense against foreign antigens entering by the mouth or nares. It has been known for a long time to be the site of colonization of important swine and zoonotic bacterial pathogens. Initially our understanding of microbes present at this site came from culture-based studies. Very recently, sequence-based approaches have been used to identify the core microbiome of the swine tonsil. Although animal to animal and herd to herd variation was detected in these studies, >90 of the organisms detected belonged to the phyla Proteobacteria and Firmicutes. Members of the family Pasteurellaceae appeared to be predominate in the tonsil; however, the relative proportions of Actinobacillus, Haemophilus, and Pasteurella varied. Members of the families Moraxellaceae, Fusobacteriaceae, Veillonellaceae, and Neisseriaceae were also seen as frequent residents of the tonsil.
The onset of impulsive bursty reconnection at a two-dimensional current layer
Authors: Fuentes-Fernández J. , Parnell C. E. , Priest E. R.
Published: July 2012

The sudden reconnection of a non-force free 2D current layer, embedded in a low-beta plasma, triggered by the onset of an anomalous resistivity, is studied in detail. The resulting behaviour consists of two main phases. First, a transient reconnection phase, in which the current in the layer is rapidly dispersed and some flux is reconnected. This dispersal of current launches a family of small amplitude magnetic and plasma perturbations, which propagate away from the null at the local fast and slow magnetosonic speeds. The vast majority of the magnetic energy released in this phase goes into internal energy of the plasma, and only a tiny amount is converted into kinetic energy. In the wake of the outwards propagating pulses, an imbalance of Lorentz and pressure forces creates a stagnation flow which drives a regime of impulsive bursty reconnection, in which fast reconnection is turned on and off in a turbulent manner as the current density exceeds and falls below a critical value. During this phase, the null current density is continuously built up above a certain critical level, then dissipated very rapidly, and built up again, in a stochastic manner. Interestingly, the magnetic energy converted during this quasi-steady phase is greater than that converted during the initial transient reconnection phase. Again essentially all the energy converted during this phase goes directly to internal energy. These results are of potential importance for solar flares and coronal heating, and set a conceptually important reference for future 3D studies.
Coherent and spontaneous emission in the quantum free electron laser
Authors: Robb G. R. M. , Bonifacio R.
Published: July 2012

We present an analysis of quantum free electron laser (QFEL) dynamics including the effects of spontaneous emission. The effects of spontaneous emission are undesirable for coherent short-wave generation using FELs and have been shown in previous studies to limit the capabilities of classical self amplified spontaneous emission (SASE)-FELs at short wavelengths ∼1 Å due to growth of electron beam energy spread. As one of the attractive features of the QFEL is its potential as a relatively compact coherent x-ray source, it is important to understand the role of spontaneous emission, but to date there has not been a model which is capable of consistently describing the dynamics of both coherent FEL emission and incoherent spontaneous emission. In this paper, we present such a model, and use it to show that the limitations imposed by spontaneous emission on coherent FEL operation are significantly different in the quantum regime to those in the classical regime. An example set of parameters constituting a QFEL using electron and laser parameters which satisfy the condition for neglect of spontaneous emission during coherent QFEL emission is presented.
Counterpropagating Rossby waves in confined plane wakes
Authors: Biancofiore L. , Gallaire F.
Published: July 2012

In the present work, we revisit the temporal and the spatio-temporal stability of confined plane wakes under the perspective of the counterpropagating Rossby waves (CRWs). Within the context of broken line velocity profiles, each vorticity discontinuity can be associated to a counterpropagating Rossby wave. In the case of a wake modeled by a broken line profile, the interaction of two CRWs is shown to originate in a shear instability. Following this description, we first recover the stability results obtained by Juniper [J. Fluid Mech. 590, 163–185 (2007)]10.1017/S0022112007007975 and Biancofiore and Gallaire [Phys. Fluids 23, 034103 (2011)]10.1063/1.3554764 by means of the classical normal mode analysis. In this manner, we propose an explanation of the stabilizing influence of the confinement on the temporal stability properties. The CRW description further allows us to propose a new interpretation of the counterintuitive spatio-temporal destabilization in wake flows at moderate confinement noticed by Juniper [J. Fluid Mech. 565, 171–195 (2006)]10.1017/S0022112006001558: it is well predicted by the mean group velocity of the uncoupled CRWs.
On the anomalous diffusion in nonisothermal plasma
Authors: Rukhadze A. A. , Sadykova S. P.
Published: July 2012

In nonisothermal plasmas at temperature Te≫Ti diffusion plays a decisive role at conditions of smooth inhomogeneity when the inhomogeneity size is much larger than Te/Ti times the Debye radius. When the inhomogeneity is rather abrupt and this condition is violated, then during the spreading process the Maxwellian relaxation of ion charges becomes significant. Here, we consider these two phenomena together and refer to the anomalous character of diffusion, i.e., anomalous diffusion.
Coarse graining of star-polymer – colloid nanocomposites
Authors: Marzi Daniela , Likos Christos N. , Capone Barbara
Published: July 2012

We consider mixtures of self-avoiding multiarm star polymers with hard colloids that are smaller than the star polymer size. By employing computer simulations, and by extending previous theoretical approaches, developed for the opposite limit of small star polymers [A. Jusufi et al., J. Phys.: Condens. Matter 13, 6177 (2001)10.1088/0953-8984/13/28/303], we coarse-grain the mixture by deriving an effective cross-interaction between the unlike species. The excellent agreement between theory and simulation for all size ratios examined demonstrates that the theoretical approaches developed for the colloidal limit can be successfully modified to maintain their validity also for the present case of the protein limit, in contrast to the situation for mixtures of colloids and linear polymers. We further analyze, on the basis of the derived interactions, the non-additivity parameter of the mixture as a function of size ratio and star functionality and delineate the regions in which we expect mixing as opposed to demixing behavior. Our results are relevant for the study of star-colloid nanocomposites and pave the way for further investigations of the structure and thermodynamics of the same.
Matrix-isolation infrared studies of 1:1 molecular complexes containing chloroform (CHCl3) and Lewis bases: Seamless transition from blue-shifted to red-shifted hydrogen bonds
Authors: Ito Fumiyuki
Published: July 2012

The infrared spectra of molecular complexes containing chloroform (CHCl3) and Lewis bases (N2, CO, H2O, and CH3CN) have been observed in an Ar matrix, and vibrational peaks for the 1:1 complexes have been assigned. The C–H stretching band of chloroform in the complexes showed a seamless transition from a blue shift (for N2 and CO) to a red shift (H2O and CH3CN), in accord with the proton affinity of the base molecules. Density functional calculations predicted that the C–H· ·(σ-type lone pair) isomer is the most stable, which is consistent with the observed vibrational peak shift upon complex formation. The underlying mechanisms of the C–H hydrogen bond were explored using the topological properties of the electronic charge density and natural orbital analyses.
Theory of repulsive charged colloids in slit-pores
Authors: Gallardo Alberto , Grandner Stefan , Almarza Noé G. , Klapp Sabine H. L.
Published: July 2012

Using classical density functional theory (DFT) we analyze the structure of the density profiles and solvation pressures of negatively charged colloids confined in slit pores. The considered model, which was already successfully employed to study a real colloidal (silica) suspension [S. H. L. Klapp et al., Phys. Rev. Lett. 100, 118303 (2008)10.1103/PhysRevLett.100.118303], involves only the macroions which interact via the effective Derjaguin-Landau-Verwey-Overbeek (DLVO) potential supplemented by a hard core interaction. The solvent enters implicitly via the screening length of the DLVO interaction. The free energy functional describing the colloidal suspension consists of a hard sphere contribution obtained from fundamental measure theory and a long range contribution which is treated using two types of approximations. One of them is the mean field approximation (MFA) and the remaining is based on Rosenfeld's perturbative method for constructing the Helmholtz energy functional. These theoretical calculations are carried out at different bulk densities and wall separations to compare finally to grand canonical Monte Carlo simulations. We also consider the impact of charged walls. Our results show that the perturbative DFT method yields generally qualitatively consistent and, for some systems, also quantitatively reliable results. In MFA, on the other hand, the neglect of charge-induced correlations leads to a breakdown of this approach in a broad range of densities.
Spin-glass behavior of Cr-doped YMnO3 compounds
Authors: Yoo Y. J. , Lee Y. P. , Park J. S. , Kang J.-H. , Kim J. , Lee B. W. , Seo M. S.
Published: July 2012

Structural and magnetic properties of polycrystalline YMn1−xCrxO3 with x = 0, 0.05, and 0.1, which was prepared by solid-state method, have been investigated. The x-ray diffraction patterns reveal that all the samples are in single phase and show hexagonal structure with P63cm space group. The temperature dependence of magnetization presents that the Cr-doped samples exhibit increase of the ferromagnetic transition temperature due to the double-exchange interaction between Cr3+ and Mn3+ ions. The magnetic hysteresis loops show weak ferromagnetic behavior. The long-time relaxation of magnetization indicates that the Cr dopants favor the spin-glass phase.
Disappearance and recovery of luminescence in GdPO4:Eu3+ nanorods: Propose to water/OH• release under near infrared and gamma irradiations
Authors: Sahu Niroj Kumar , Ningthoujam R. S. , Bahadur D.
Published: July 2012

Luminescence intensity of rare-earth doped materials can be varied depending on shape of particles, capping agent, and heat-treatment. This is related to the non-radiative rate possessed by the material. Here, we observed the high quenching of the luminescence intensity of Eu3+ doped GdPO4 prepared in water (H2O) medium. On the contrary, in ethylene glycol (EG) medium, it shows high luminescence. Luminescence intensity is recovered when Eu3+ doped GdPO4 nanorods prepared in H2O medium is heated above 700 °C. This transforms hexagonal to monoclinic structure following the removal of water. Luminescence intensity is enhanced by changing the medium from H2O to D2O and also if core-shell formation occurs. Also, we found significant variation in bending and stretching vibrations of O-H and microstructure in this material prepared in H2O and EG. Two types of O-H stretching frequencies are observed at 3450 and 3520 cm−1 in H2O medium prepared sample which are assigned to the O-H having the hydrogen bonding (surface water) and the confined water, respectively. The formation of nanorods is due to the presence of water on the surface of particles or/and inside the pores of compound. The available water in the nanoparticles pores can be utilized for the efficient killing of mass cells tumor by generating reactive free radicals (H· and OH·) through the application of laser near infrared (NIR) source and the subsequent irradiation of gamma ray. This proposed mechanism is quite different from the conventional treatment of mass cell/malignant tumor using gamma ray radiation. Sample is highly paramagnetic and it will be useful for magnetic resonance imaging contrast agent.
Modeling analysis and experimental study on the optical fiber hydrogen sensor based on Pd-Y alloy thin film
Authors: Liu Yi , Chen You-ping , Song Han , Zhang Gang
Published: July 2012

The failure of hydrogen sensor with palladium film is primarily the phase transition of PdH. To restrain this, a novel palladium and yttrium (Pd-Y) alloy film was prepared by the co-sputtering method and was used to design an optical fiber hydrogen sensor. A sensor model was established based on the optical film matrix method. The relationship between the reflectivity of the film and the hydrogen concentration was discussed. The experimental results show that this sensor is superior to the traditional sensor with Pd in shortening the response and recovery time, restraining drift, and promoting repeatability. The Pd-Y alloy film is an extremely promising material for detecting hydrogen.
Dynamic compressive behavior of Pr-Nd alloy at high strain rates and temperatures
Authors: Wang Huanran , Cai Canyuan , Chen Danian , Ma Dongfang
Published: July 2012

Based on compressive tests, static on 810 material test system and dynamic on the first compressive loading in split Hopkinson pressure bar (SHPB) tests for Pr-Nd alloy cylinder specimens at high strain rates and temperatures, this study determined a J-C type [G. R. Johnson and W. H. Cook, in Proceedings of Seventh International Symposium on Ballistics (The Hague, The Netherlands, 1983), pp. 541–547] compressive constitutive equation of Pr-Nd alloy. It was recorded by a high speed camera that the Pr-Nd alloy cylinder specimens fractured during the first compressive loading in SHPB tests at high strain rates and temperatures. From high speed camera images, the critical strains of the dynamic shearing instability for Pr-Nd alloy in SHPB tests were determined, which were consistent with that estimated by using Batra and Wei’s dynamic shearing instability criterion [R. C. Batra and Z. G. Wei, Int. J. Impact Eng. 34, 448 (2007)] and the determined compressive constitutive equation of Pr-Nd alloy. The transmitted and reflected pulses of SHPB tests for Pr-Nd alloy cylinder specimens computed with the determined compressive constitutive equation of Pr-Nd alloy and Batra and Wei’s dynamic shearing instability criterion could be consistent with the experimental data. The fractured Pr-Nd alloy cylinder specimens of compressive tests were investigated by using 3D supper depth digital microscope and scanning electron microscope.
Nanomodification of gold surface by picosecond soft x-ray laser pulse
Authors: Norman Genri , Starikov Sergey , Stegailov Vladimir , Fortov Vladimir , Skobelev Igor , Pikuz Tatyana , Faenov Anatoly , Tamotsu Sataoshi , Kato Yoshiaki , Ishino Masahiko , Tanaka Momoko , Hasegawa Noboru , Nishikino Masaharu , Ohba Toshiuki , Kaihori Takeshi , Ochi Yoshihiro , Imazono Takashi , Fukuda Yuji , Kando Masaki , Kawachi Tetsuya
Published: July 2012

We show experimentally the possibility of nanostructuring (about 20 nm) of gold surface by picosecond soft x-ray single pulse with low fluence of ∼20 mJ/cm2. The nanometer-scale changes of the surface structure are due to the splash of molten gold under fluence gradient of the laser beam. In addition, the ablation process occurs at slightly higher fluence of ∼50 mJ/cm2. The atomistic model of ablation is developed which reveals that the low threshold fluence of this process is due to the build-up of the high electron pressure and the comparatively low electron-ion energy relaxation rate in gold. The calculated ablation depths as a function of the irradiation fluence are in good agreement with the experimental data measured for gold surface modification with ultra-short duration soft x-ray and visible lasers.
Nonlinear damage effect in graphene synthesis by C-cluster ion implantation
Authors: Zhang Rui , Zhang Zaodi , Wang Zesong , Wang Shixu , Wang Wei , Fu Dejun , Liu Jiarui
Published: July 2012

We present few-layer graphene synthesis by negative carbon cluster ion implantation with C1, C2, and C4 at energies below 20 keV. The small C-clusters were produced by a source of negative ion by cesium sputtering with medium beam current. We show that the nonlinear effect in cluster-induced damage is favorable for graphene precipitation compared with monomer carbon ions. The nonlinear damage effect in cluster ion implantation shows positive impact on disorder reduction, film uniformity, and the surface smoothness in graphene synthesis.
Fatigue cracking at twin boundary: Effect of dislocation reactions
Authors: Zhang Z. J. , Li L. L. , Zhang P. , Zhang Z. F.
Published: July 2012

This Letter addresses a new finding of the connection between the macroscopic fatigue cracking behaviors of twin boundaries (TBs) and the microscopic TB-dislocation interactions. According to the difference in crystallography beside TBs, slipping dislocations usually interact with TBs in different modes during plastic deformation. In this study, fatigue cracking behaviors at the TBs in Cu and Cu alloys were investigated and compared theoretically and experimentally based on these different interaction modes. The results reveal that the TB-dislocation interactions strongly affect the interfacial strength of TBs through influencing the damage degree by the penetrated dislocations during low-cycle fatigue tests.
Communication: Phase space approach to laser-driven electronic wavepacket propagation
Authors: Takemoto Norio , Shimshovitz Asaf , Tannor David J.
Published: July 2012

We propose a phase space method to propagate a quantum wavepacket driven by a strong external field. The method employs the periodic von Neumann basis with biorthogonal exchange recently introduced for the calculation of the energy eigenstates of time-independent quantum systems [A. Shimshovitz and D. J. Tannor, Phys. Rev. Lett. (in press) [e-print arXiv:1201.2299v1]]. While the individual elements in this basis set are time-independent, a small subset is chosen in a time-dependent manner to adapt to the evolution of the wavepacket in phase space. We demonstrate the accuracy and efficiency of the present propagation method by calculating the electronic wavepacket in a one-dimensional soft-core atom interacting with a superposition of an intense, few-cycle, near-infrared laser pulse and an attosecond extreme-ultraviolet laser pulse.
Laser ablation dynamics in metals: The thermal regime
Authors: Mezzapesa F. P. , Columbo L. L. , Brambilla M. , Dabbicco M. , Ancona A. , Sibillano T. , Scamarcio G.
Published: July 2012

We studied the laser ablation dynamics of steel in the thermal regime both experimentally and theoretically. The real-time monitoring of the process shows that the ablation rate depends on laser energy density and ambient pressure during the exposure time. We demonstrated that the ablation efficiency can be enhanced when the pressure is reduced with respect to the atmospheric pressure for a given laser fluence, reaching an upper limit despite of high-vacuum conditions. An analytical model based on the Hertz-Knudsen law reproduces all the experimental results.
Hall-effect mobility of pentacene films prepared by the thermal evaporating method with different substrate temperature
Authors: Lin Yow-Jon , Tsao Hou-Yen , Liu Day-Shan
Published: July 2012

We studied the Hall-effect mobility of pentacene films prepared by the thermal evaporating method with different substrate temperature. A crossover from coherent bandlike charge transport with mobilities up to several tens of cm2/V-s at low temperature to an incoherent hopping motion at high temperature is observed. The carrier mobilities of pentacene exhibit a hopping-to-band transition around room temperature. An exhibition of high mobility of pentacene films prepared with substrate temperature of 90 °C is attributed to the increased spacing between molecules.
Operational lifetime improvement of poly(9,9-dioctylfluorene) active waveguides by thermal lamination
Authors: Anni M.
Published: July 2012

We investigate the encapsulation performances of polyethylene terephthalate-poly (ethylene vinyl acetate) laminating pouches, thermally laminated on flexible poly(9,9-dioctylfluorene)(PF8) active waveguides showing amplified spontaneous emission (ASE). We show that the lamination process does not cause significant degradation of the PF8 emission properties and preserves the ASE properties of the waveguide, with an ASE threshold increase of only 15%. A clear increase of the ASE operational lifetime up to 2.3 times is observed after lamination, together with stable ASE threshold for more than 6 months after the device realization, thus proposing thermal lamination as a straightforward technique to encapsulate organic active waveguides, preserving the possibility to realize flexible devices.
Trapping of surface plasmon waves in graded grating waveguide system
Authors: Wang Guoxi , Lu Hua , Liu Xueming
Published: July 2012

We have proposed a graded grating plasmonic system with a significant slow-light effect for the propagation of high-confinement surface plasmon (SP) wave. Theoretical analysis and numerical simulations show that the localized position of SP wave in the plasmonic waveguide is dependent on the operating frequency. It is found that the slow-light effect exhibits an obvious enhancement with propagation. The proposed ultracompact configuration offers the advantage of a large trapping bandwidth of 90 THz, which may find excellent applications on slow-light systems, especially optical buffers.
Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation
Authors: Zheng Dan , Giljohann David A. , Chen David L. , Massich Matthew D. , Wang Xiao-Qi , Iordanov Hristo , Mirkin Chad A. , Paller Amy S.
Published: July 2012

Topical application of nucleic acids offers many potential therapeutic advantages for suppressing genes in the skin, and potentially for systemic gene delivery. However, the epidermal barrier typically precludes entry of gene-suppressing therapy unless the barrier is disrupted. We now show that spherical nucleic acid nanoparticle conjugates (SNA-NCs), gold cores surrounded by a dense shell of highly oriented, covalently immobilized siRNA, freely penetrate almost 100% of keratinocytes in vitro, mouse skin, and human epidermis within hours after application. Significantly, these structures can be delivered in a commercial moisturizer or phosphate-buffered saline, and do not require barrier disruption or transfection agents, such as liposomes, peptides, or viruses. SNA-NCs targeting epidermal growth factor receptor (EGFR), an important gene for epidermal homeostasis, are > 100-fold more potent and suppress longer than siRNA delivered with commercial lipid agents in cultured keratinocytes. Topical delivery of 1.5 uM EGFR siRNA (50 nM SNA-NCs) for 3 wk to hairless mouse skin almost completely abolishes EGFR expression, suppresses downstream ERK phosphorylation, and reduces epidermal thickness by almost 40%. Similarly, EGFR mRNA in human skin equivalents is reduced by 52% after 60 h of treatment with 25 nM EGFR SNA-NCs. Treated skin shows no clinical or histological evidence of toxicity. No cytokine activation in mouse blood or tissue samples is observed, and after 3 wk of topical skin treatment, the SNA structures are virtually undetectable in internal organs. SNA conjugates may be promising agents for personalized, topically delivered gene therapy of cutaneous tumors, skin inflammation, and dominant negative genetic skin disorders.
Supramodal numerosity selectivity of neurons in primate prefrontal and posterior parietal cortices
Authors: Nieder Andreas
Published: July 2012

Numerosity, the number of elements in a set, is a most abstract quantitative category. As such, it is independent of the sensory modality of its elements, i.e., supramodal. Because neuronal numerosity selectivity had never been compared directly across different sensory modalities, it remained elusive if and where single neurons encode numerosity irrespective of the items’ modality. Here, monkeys were trained to discriminate both the number of auditory sounds and visual items within the same session. While the monkeys performed this task, the activity of neurons was recorded in the lateral prefrontal cortex and ventral intraparietal sulcus, structures critically involved in numerical cognition. Groups of neurons in both areas encoded either the number of auditory pulses, visual items, or both. The finding of neurons responding to numerosity irrespective of the sensory modality supports the idea of a nonverbal, supramodal neuronal code of numerical quantity in the primate brain.
Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis
Authors: Blanc Lionel , Ciciotte Steven L. , Gwynn Babette , Hildick-Smith Gordon J. , Pierce Eric L. , Soltis Kathleen A. , Cooney Jeffrey D. , Paw Barry H. , Peters Luanne L.
Published: July 2012

Phenotype-driven approaches to gene discovery using inbred mice have been instrumental in identifying genetic determinants of inherited blood dyscrasias. The recessive mutant
scat
(severe combined anemia and thrombocytopenia) alternates between crisis and remission episodes, indicating an aberrant regulatory feedback mechanism common to erythrocyte and platelet formation. Here, we identify a missense mutation (G125V) in the
scat Rasa3
gene, encoding a Ras GTPase activating protein (RasGAP), and elucidate the mechanism producing crisis episodes. The mutation causes mislocalization of RASA3 to the cytosol in
scat
red cells where it is inactive, leading to increased GTP-bound Ras. Erythropoiesis is severely blocked in
scat
crisis mice, and ∼94% succumb during the second crisis (∼30 d of age) from catastrophic hematopoietic failure in the spleen and bone marrow. Megakaryopoiesis is also defective during crisis. Notably, the
scat
phenotype is recapitulated in zebrafish when
rasa3
is silenced. These results highlight a critical, conserved, and nonredundant role for RASA3 in vertebrate hematopoiesis.
Tetradian oscillation of estrogen receptor α is necessary to prevent liver lipid deposition
Authors: Villa Alessandro , Della Torre Sara , Stell Alessia , Cook Jennifer , Brown Myles , Maggi Adriana
Published: July 2012

In the liver of female mice, the transcriptional activity of estrogen receptor (ER) α oscillates in phase with the 4-d-long estrous cycle. Here systemic, genome-wide analysis demonstrates that ER tetradian oscillation is necessary to generate pulses of expression in genes for fatty acid and cholesterol synthesis. This ER-dependent metabolic programming changes with pregnancy and after cessation of ovarian function due to age or surgical menopause, suggesting that ER signaling is optimized to coordinate liver functions with the energetic requirements of each reproductive stage. Alterations of amplitude and frequency of the tetradian cycle, as observed after surgical menopause, age, or specific ablation of the hepatic
Igf-1
gene, are associated with liver fat deposition. Appropriate hormone replacement therapy reinstating the oscillatory activity of liver ER prevents the effect of surgical menopause on fat deposition in liver.
Heterogeneous networks do not promote cooperation when humans play a Prisoner’s Dilemma
Authors: Gracia-Lázaro Carlos , Ferrer Alfredo , Ruiz Gonzalo , Tarancón Alfonso , Cuesta José A. , Sánchez Angel , Moreno Yamir
Published: July 2012

It is not fully understood why we cooperate with strangers on a daily basis. In an increasingly global world, where interaction networks and relationships between individuals are becoming more complex, different hypotheses have been put forward to explain the foundations of human cooperation on a large scale and to account for the true motivations that are behind this phenomenon. In this context, population structure has been suggested to foster cooperation in social dilemmas, but theoretical studies of this mechanism have yielded contradictory results so far; additionally, the issue lacks a proper experimental test in large systems. We have performed the largest experiments to date with humans playing a spatial Prisoner’s Dilemma on a lattice and a scale-free network (1,229 subjects). We observed that the level of cooperation reached in both networks is the same, comparable with the level of cooperation of smaller networks or unstructured populations. We have also found that subjects respond to the cooperation that they observe in a reciprocal manner, being more likely to cooperate if, in the previous round, many of their neighbors and themselves did so, which implies that humans do not consider neighbors’ payoffs when making their decisions in this dilemma but only their actions. Our results, which are in agreement with recent theoretical predictions based on this behavioral rule, suggest that population structure has little relevance as a cooperation promoter or inhibitor among humans.
Phenanthriplatin, a monofunctional DNA-binding platinum anticancer drug candidate with unusual potency and cellular activity profile
Authors: Park Ga Young , Wilson Justin J. , Song Ying , Lippard Stephen J.
Published: July 2012

Monofunctional platinum(II) complexes of general formula
cis
-[Pt(NH
3
)
2
(
N
-heterocycle)Cl]Cl bind DNA at a single site, inducing little distortion in the double helix. Despite this behavior, these compounds display significant antitumor properties, with a different spectrum of activity than that of classic bifunctional cross-linking agents like cisplatin. To discover the most potent monofunctional platinum(II) compounds, the
N
-heterocycle was systematically varied to generate a small library of new compounds, with guidance from the X-ray structure of RNA polymerase II (Pol II) stalled at a monofunctional pyriplatin-DNA adduct. In pyriplatin, the
N
-heterocycle is pyridine. The most effective complex evaluated was phenanthriplatin,
cis
-[Pt(NH
3
)
2
(phenanthridine)Cl]NO
3
, which exhibits significantly greater activity than the Food and Drug Administration-approved drugs cisplatin and oxaliplatin. Studies of phenanthriplatin in the National Cancer Institute 60-cell tumor panel screen revealed a spectrum of activity distinct from that of these clinically validated anticancer agents. The cellular uptake of phenanthriplatin is substantially greater than that of cisplatin and pyriplatin because of the hydrophobicity of the phenanthridine ligand. Phenanthriplatin binds more effectively to 5′-deoxyguanosine monophosphate than to
N
-acetyl methionine, whereas pyriplatin reacts equally well with both reagents. This chemistry supports DNA as a viable cellular target for phenanthriplatin and suggests that it may avoid cytoplasmic platinum scavengers with sulfur-donor ligands that convey drug resistance. With the use of globally platinated
Gaussia
luciferase vectors, we determined that phenanthriplatin inhibits transcription in live mammalian cells as effectively as cisplatin, despite its inability to form DNA cross-links.
A critical and historical investigation into semantic prosody
Authors: Smith K. Aaron , Nordquist Dawn
Published: July 2012

While existing literature on cause frequently cites the negative meaning associated with that lexeme, i.e. the fact that cause tends to appear with a negative outcome, e.g. cause an accident, really no scholar has studied in any detail the historical development of the phenomenon. In order to address this missing line of scholarship concerning the diachronic development of, what we refer to here as, a semantic prosody, this paper presents a fine-grained historical study of the development of the negative semantic associations of cause by comparing tokens from the Early Modern English period to those from Present-day English. We are able to conclude that the semantic prosody involved with cause is an emergent diachronic phenomenon. In addition, we are also able to argue that it is at the level of construction that such a prosodic pattern operates. Following from the notion that the semantic prosody is a construction-level phenomenon, we offer an exemplar-based model to motivate certain of the diachronic and synchronic facts.
TLM-Tracker: software for cell segmentation, tracking and lineage analysis in time-lapse microscopy movies
Authors: Klein Johannes , Leupold Stefan , Biegler Ilona , Biedendieck Rebekka , Münch Richard , Jahn Dieter
Published: July 2012

Motivation: Time-lapse imaging in combination with fluorescence microscopy techniques enable the investigation of gene regulatory circuits and uncovered phenomena like culture heterogeneity. In this context, computational image processing for the analysis of single cell behaviour plays an increasing role in systems biology and mathematical modelling approaches. Consequently, we developed a software package with graphical user interface for the analysis of single bacterial cell behaviour.

Results: A new software called TLM-Tracker allows for the flexible and user-friendly interpretation for the segmentation, tracking and lineage analysis of microbial cells in time-lapse movies.

Availability: The software package, including manual, tutorial video and examples, is available as Matlab code or executable binaries at http://www.tlmtracker.tu-bs.de.

Contact:  r.muench@tu-bs.de
Otolith microstructure analysis to resolve seasonal patterns of hatching and settlement in western Baltic cod
Authors: Rehberg-Haas Sabine , Hammer Cornelius , Hillgruber Nicola , Hüssy Karin , Temming Axel
Published: July 2012

Rehberg-Haas, S., Hammer, C., Hillgruber, N., Hüssy, K., and Temming, A. 2012. Otolith microstructure analysis to resolve seasonal patterns of hatching and settlement in western Baltic cod. – ICES Journal of Marine Science, 69: . Previous studies showed that Baltic cod (Gadus morhua) settle to demersal life at a given size, while the annulus is formed seasonally, irrespective of size. The goal of this study was to examine the timing of check formation in juvenile Baltic cod otoliths to validate macrostructural ageing and to differentiate between true annuli and secondary structures such as settlement checks. Otoliths were collected from fish off Fehmarn Island in 2008 and 2009, and were examined for macrostructural and microstructural patterns using light and scanning electron microscopy. All fish examined were age-0. Back-calculation of hatch dates indicated hatching from April to June and from February to August in 2008 and 2009, respectively. Juveniles formed either one or two translucent rings. The first translucent ring started to form ∼3 months post-hatch and was interpreted as a settlement check, since it appeared to be a function of age and/or size and not season. Deposition of the second ring began in mid October to early November irrespective of fish size and/or age, thus indicating that this ring may represent the first annulus of Baltic cod. Both rings were clearly distinguishable in individuals hatched between February and May, but were merged in those fish where settlement coincided with the seasonally formed second ring.
An efficient shock capturing scheme for multicomponent multiphase thermal flow in porous media
Authors: van Odyck Daniel E. A. , Lovett Sean , Monmont Franck , Nikiforakis Nikolaos
Published: July 2012

This paper is concerned with multicomponent, two-phase, thermal fluid flow in porous media. The fluid model consists of component conservation equations, Darcy's law for volumetric flow rates and an enthalpy conservation equation. The model is closed with an equation of state and phase equilibrium conditions that determine the distribution of the chemical components into phases. The sequential formulation described in a previous article is used to build a second-order shock capturing scheme for the conservation equations using a primitive-variable-based linear reconstruction. The fluxes at the cell faces are calculated using an approximate Riemann solver. The method is validated and evaluated by means of one- and two-dimensional problems, including a gravity inversion test.
Kribbella endophytica sp. nov., an endophytic actinobacterium isolated from the surface-sterilized leaf of a native apricot tree
Authors: Kaewkla Onuma , Franco Christopher M. M.
Published: July 2012

A new strain of the genus

Kribbella

, PIP 118T, was isolated from the leaf of an Australian native apricot tree (Pittosporum angustifolium), or Gumbi Gumbi in the indigenous language. This strain is an aerobic actinobacterium consisting of hyphae that fragment into short to elongated rod-like elements. Phylogenetic evaluation based on 16S rRNA gene sequence analysis placed this isolate as a member of the family

Nocardioidaceae

and most closely related to

Kribbella antibiotica

YIM 31530T (98.6 %) and

Kribbella koreensis

LM 161T (98.4 %). Chemotaxonomic data including cell wall components, major menaquinone and major fatty acids confirmed the affiliation of strain PIP 118T to the genus

Kribbella

. The results of the phylogenetic analysis, including physiological and biochemical studies in combination with DNA–DNA hybridization, allowed the genotypic and phenotypic differentiation of strain PIP 118T and members of the most closely related species with validly published names. The name proposed for the new species is Kribbella endophytica sp. nov. The type strain is PIP 118T ( = DSM 23718T = NRRL B-24812T).
Aquimarina longa sp. nov., isolated from seawater, and emended description of

Aquimarina muelleri
Authors: Yu Tong , Yin Qi , Song Xiangyu , Zhao Rui , Shi Xiaochong , Zhang Xiao-Hua
Published: July 2012

A novel Gram-stain-negative, rod-shaped, non-flagellated, strictly aerobic strain with gliding motility, designated SW024T, was isolated from surface seawater of the South Pacific Gyre (26° 29′ S 137° 56′ W) during the Integrated Ocean Drilling Program Expedition 329. Phylogenetic analyses based on 16S rRNA gene sequences showed that the novel strain was related most closely to

Aquimarina muelleri

KMM 6020T,

Aquimarina macrocephali

JAMB N27T,

Aquimarina addita

JC2680T,
Aquimarina mytili PSC33T,

Aquimarina intermedia

KMM 6258T,

Aquimarina latercula

ATCC 23177T,

Aquimarina spongiae

A6T,

Aquimarina agarilytica

ZC1T and

Aquimarina brevivitae

SMK-19T (96.1, 95.5, 95.0, 94.4, 94.3, 94.0, 93.4, 93.3 and 93.2 % similarities, respectively), demonstrating that the novel strain belonged to the genus

Aquimarina

. The DNA G+C content of strain SW024T was 30.8 mol%. The major respiratory quinone of strain SW024T was MK-6. The dominant fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 1 G, C16 : 0 10-methyl and/or iso-C17 : 1ω9c, and iso-C15 : 0 3-OH. The polar lipids of strain SW024T were phosphatidylethanolamine, three unknown aminolipids and five unknown polar lipids. On the basis of combined phenotypic and phylogenetic analyses, strain SW024T represents a novel species of the genus

Aquimarina

, for which the name Aquimarina longa sp. nov. is proposed. The type strain is SW024T ( = CGMCC 1.11007T = JCM 17859T). An emended description of

A. muelleri

is also proposed.
Luteimonas vadosa sp. nov., isolated from seashore sediment
Authors: Romanenko Lyudmila A. , Tanaka Naoto , Svetashev Vassilii I. , Kurilenko Valeriya V. , Mikhailov Valery V.
Published: July 2012

An aerobic, Gram-stain-negative, yellow-pigmented, non-motile, rod-shaped bacterium designated strain KMM 9005Twas isolated from a sediment sample collected from the Sea of Japan seashore. Comparative 16S rRNA gene sequence analysis showed that strain KMM 9005Tbelonged to the genusLuteimonasand was most closely related toLuteimonas cucumerisKCTC 23627T(96.5 % sequence similarity) andLuteimonas aquaticaLMG 24212T(96.1 % sequence similarity). Strain KMM 9005Twas characterized by the presence of thin fimbriae, the major ubiquinone Q-8, by the predominance of iso-C17 : 1followed by iso-C16 : 0, iso-C15 : 0and iso-C17 : 0in its fatty acid profile, weak hydrolytic capacity and the inability to assimilate most organic substrates. Based on these distinctive phenotypic characteristics and phylogenetic analysis, strain KMM 9005Trepresents a novel species of the genusLuteimonas, for which the nameLuteimonas vadosasp. nov. is proposed. The type strain is KMM 9005T( = NRIC 0881T = JCM 18392T).
A Src family kinase–Shp2 axis controls RUNX1 activity in megakaryocyte and T-lymphocyte differentiation
Authors: Huang Hui , Woo Andrew J. , Waldon Zachary , Schindler Yocheved , Moran Tyler B. , Zhu Helen H. , Feng Gen-Sheng , Steen Hanno , Cantor Alan B.
Published: July 2012

Hematopoietic development occurs in complex microenvironments and is influenced by key signaling events. Yet how these pathways communicate with master hematopoietic transcription factors to coordinate differentiation remains incompletely understood. The transcription factor RUNX1 plays essential roles in definitive hematopoietic stem cell (HSC) ontogeny, HSC maintenance, megakaryocyte (Mk) maturation, and lymphocyte differentiation. It is also the most frequent target of genetic alterations in human leukemia. Here, we report that RUNX1 is phosphorylated by Src family kinases (SFKs) and that this occurs on multiple tyrosine residues located within its negative regulatory DNA-binding and autoinhibitory domains. Retroviral transduction, chemical inhibitor, and genetic studies demonstrate a negative regulatory role of tyrosine phosphorylation on RUNX1 activity in Mk and CD8 T-cell differentiation. We also demonstrate that the nonreceptor tyrosine phosphatase Shp2 binds directly to RUNX1 and contributes to its dephosphorylation. Last, we show that RUNX1 tyrosine phosphorylation correlates with reduced GATA1 and enhanced SWI/SNF interactions. These findings link SFK and Shp2 signaling pathways to the regulation of RUNX1 activity in hematopoiesis via control of RUNX1 multiprotein complex assembly.