Spi-1, Fli-1 and Fli-3 (miR-17-92) Oncogenes Contribute to a Single Oncogenic Network Controlling Cell Proliferation in Friend Erythroleukemia

Clonal erythroleukemia developing in susceptible mice infected by Friend virus complex are associated with highly recurrent proviral insertions at one of three loci called Spi-1, Fli-1 or Fli-3, leading to deregulated expression of oncogenic Spi-1 or Fli-1 transcription factors or miR-17-92 miRNA cluster, respectively. Deregulated expression of each of these three oncogenes has been independently shown to contribute to cell proliferation of erythroleukemic clones. Previous studies showed a close relationship between Spi-1 and Fli-1, which belong to the same ETS family, Spi-1 activating fli-1 gene, and both Spi-1 and Fli-1 activating multiple common target genes involved in ribosome biogenesis. In this study, we demonstrated that Spi-1 and Fli-1 are also involved in direct miR-17-92 transcriptional activation through their binding to a conserved ETS binding site in its promoter. Moreover, we demonstrated that physiological re-expression of exogenous miR-17 and miR-20a are able to partially rescue the proliferation loss induced by Fli-1 knock-down and identified HBP1 as a target of these miRNA in erythroleukemic cells. These results establish that three of the most recurrently activated oncogenes in Friend erythroleukemia are actually involved in a same oncogenic network controlling cell proliferation. The putative contribution of a similar ETS-miR-17-92 network module in other normal or pathological proliferative contexts is discussed

Renal ischemia and reperfusion activates the eIF2 alpha kinase PERK

Inhibition of protein synthesis occurs in the post-ischemic reperfused kidney but the molecular mechanism of renal translation arrest is unknown. Several pathways have been identified whereby cell stress inhibits translation initiation via phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF2a, phospho-form eIF2a(P)]. Here, we report a 20-fold increase in eIF2a(P) in kidney homogenates following 10 min of cardiac arrest-induced ischemia and 10 min reperfusion. Using immunohistochemistry, we observed eIF2a(P) in tubular epithelial cells in both cortex and medulla, where the greatest eIF2a(P) staining was found in epithelial cells of the so-called watershed area at the corticomedullary junction. We further show that increased eIF2a(P) is accompanied by activation of the PKR-like endoplasmic reticulum eIF2a kinase (PERK). These observations indicate that renal ischemia and reperfusion induce stress to the endoplasmic reticulum and activate the unfolded protein response in renal epithelial cells. As the unfolded protein response can result alternatively in a pro-survival or pro-apoptotic outcome, the present study demonstrates an new additional mechanism involved in cell damage and/or repair in ischemic and reperfused kidney. © 2005 Elsevier B.V. All rights reserved

Landspotting: Social gaming to collect vast amounts of data for satellite validation

At present there is no single satellite-derived global land cover product that is accurate enough to provide reliable estimates of forest or cropland area to determine, e.g., how much additional land is available to grow biofuels or to tackle problems of food security. The Landspotting Project aims to improve the quality of this land cover information by vastly increasing the amount of in-situ validation data available for calibration and validation of satellite-derived land cover. The Geo-Wiki (Geo-Wiki.org) system currently allows users to compare three satellite derived land cover products and validate them using Google Earth. However, there is presently no incentive for anyone to provide this data so the amount of validation through Geo-Wiki has been limited. However, recent competitions have proven that incentive driven campaigns can rapidly create large amounts of input. The LandSpotting Project is taking a truly innovative approach through the development of the Landspotting game. The game engages users whilst simultaneously collecting a large amount of in-situ land cover information. The development of the game is informed by the current raft of successful social gaming that is available on the internet and as mobile applications, many of which are geo-spatial in nature. Games that are integrated within a social networking site such as Facebook illustrate the power to reach and continually engage a large number of individuals. The number of active Facebook users is estimated to be greater than 400 million, where 100 million are accessing Facebook from mobile devices. The Landspotting Game has similar game mechanics as the famous strategy game "Civilization" (i.e. build, harvest, research, war, diplomacy, etc.). When a player wishes to make a settlement, they must first classify the land cover over the area they wish to settle. As the game is played on the earth surface with Google Maps, we are able to record and store this land cover/land use classification geographically. Every player can play the game for free (i.e. a massive multiplayer online game). Furthermore, it is a social game on Facebook (e.g. invite friends, send friends messages, purchase gifts, help friends, post messages onto the wall, etc). The game is played in a web browser, therefore it runs everywhere (where Flash is supported) without requiring the user to install anything additional. At the same time, the Geo-Wiki system will be modified to use the acquired in-situ validation information to create new outputs: a hybrid land cover map, which takes the best information from each individual product to create a single integrated version; a database of validation points that will be freely available to the land cover user community; and a facility that allows users to create a specific targeted validation area, which will then be provided to the crowdsourcing community for validation. These outputs will turn Geo-Wiki into a valuable system for earth system scientists

Interaction of mesoscopic magnetic textures with superconductors

Journals published by the American Physical Society can be found at http://journals.aps.org/Here we report a method to calculate the vortex and magnetization arrangement for a system of interacting superconductors and ferromagnets separated in space. The method is based on static London-Maxwell equations and the corresponding energy. Possible superconducting vortices are included in this system. Using this method we analyze screening currents in a superconducting film induced by magnetic textures in a thin magnetic film. We assume that the two films are parallel and positioned close to each to other, but interact exclusively via magnetic fields. We also consider possible vortices within this superconducting film and their interactions with magnetic texture. As an example of such magnetic texture we use a single magnetic dot with magnetization either perpendicular or parallel to the film. We derive a condition where spontaneous formation of one, two, or more vortices and antivortices is energetically favorable. We prove that, in the case of such a circular magnetic dot with perpendicular magnetization, when the vortex emerges in the superconducting film the normal component of magnetic field near the superconducting film changes sign outside of the dot range

Game-Based Rehabilitation for Myoelectric Prosthesis Control

Background: A high number of upper extremity myoelectric prosthesis users abandon their devices due to difficulties in prosthesis control and lack of motivation to train in absence of a physiotherapist. Virtual training systems, in the form of video games, provide patients with an entertaining and intuitive method for improved muscle coordination and improved overall control. Complementary to established rehabilitation protocols, it is highly beneficial for this virtual training process to start even before receiving the final prosthesis, and to be continued at home for as long as needed. Objective: The aim of this study is to evaluate (1) the short-term effects of a commercially available electromyographic (EMG) system on controllability after a simple video game-based rehabilitation protocol, and (2) different input methods, control mechanisms, and games. Methods: Eleven able-bodied participants with no prior experience in EMG control took part in this study. Participants were asked to perform a surface EMG test evaluating their provisional maximum muscle contraction, fine accuracy and isolation of electrode activation, and endurance control over at least 300 seconds. These assessments were carried out (1) in a Pregaming session before interacting with three EMG-controlled computer games, (2) in a Postgaming session after playing the games, and (3) in a Follow-Up session two days after the gaming protocol to evaluate short-term retention rate. After each game, participants were given a user evaluation survey for the assessment of the games and their input mechanisms. Participants also received a questionnaire regarding their intrinsic motivation (Intrinsic Motivation Inventory) at the end of the last game. Results: Results showed a significant improvement in fine accuracy electrode activation (P<.01), electrode separation (P=.02), and endurance control (P<.01) from Pregaming EMG assessments to the Follow-Up measurement. The deviation around the EMG goal value diminished and the opposing electrode was activated less frequently. Participants had the most fun playing the games when collecting items and facing challenging game play. Conclusions: Most upper limb amputees use a 2-channel myoelectric prosthesis control. This study demonstrates that this control can be effectively trained by employing a video game-based rehabilitation protocol.(VLID)486422

Magnetic Pinning of Vortices in a Superconducting Film: The (anti)vortex-magnetic dipole interaction energy in the London approximation

The interaction between a superconducting vortex or antivortex in a superconducting film and a magnetic dipole with in- or out-of-plane magnetization is investigated within the London approximation. The dependence of the interaction energy on the dipole-vortex distance and the film thickness is studied and analytical results are obtained in limiting cases. We show how the short range interaction with the magnetic dipole makes the co-existence of vortices and antivortices possible. Different configurations with vortices and antivortices are investigated.Comment: 12 pages, 12 figures. Submitted to Phys. Rev.

Magnetic Properties of 2-Dimensional Dipolar Squares: Boundary Geometry Dependence

By means of the molecular dynamics simulation on gradual cooling processes, we investigate magnetic properties of classical spin systems only with the magnetic dipole-dipole interaction, which we call dipolar systems. Focusing on their finite-size effect, particularly their boundary geometry dependence, we study two finite dipolar squares cut out from a square lattice with $\Phi=0$ and $\pi/4$, where $\Phi$ is an angle between the direction of the lattice axis and that of the square boundary. Distinctly different results are obtained in the two dipolar squares. In the $\Phi=0$ square, the ``from-edge-to-interior freezing'' of spins is observed. Its ground state has a multi-domain structure whose domains consist of the two among infinitely (continuously) degenerated Luttinger-Tisza (LT) ground-state orders on a bulk square lattice, i.e., the two antiferromagnetically aligned ferromagnetic chains (af-FMC) orders directed in parallel to the two lattice axes. In the $\Phi=\pi/4$ square, on the other hand, the freezing starts from the interior of the square, and its ground state is nearly in a single domain with one of the two af-FMC orders. These geometry effects are argued to originate from the anisotropic nature of the dipole-dipole interaction which depends on the relative direction of sites in a real space of the interacting spins.Comment: 21 pages, 13 figures, submitted to Journal of Physical Society Japa

Investigation on the aerosol performance of dry powder inhalation hypromellose capsules with different lubricant levels

HPMC capsules are made by a dipping process and a surface lubricant for the mould pins is an essential processing aid for removing dried capsules shells. For the purpose of this study, the level was determined by quantifying methyloleate (MO) a component found in the lubricant but not in the hypromellose capsules. Here we investigated the influence of the lubricant, low (10.81 μg/capsule = 60 mg/kg MO), medium (15.97 μg/capsule = 90 mg/kg MO) and high (23.23 μg/capsule = 127 mg/kg MO) content on powder (binary mixture of salbutamol: lactose, 1:50 w/w) aerosolization properties was investigated. Results indicated significantly lower emitted dose from capsules with 60 mg/kg MO. Furthermore, the 90 and 127 mg/kg MO level of lubricant capsules produced almost double the Fine Particle Dose & Fine Particle Fraction compared with the low level of lubricant. The data indicates that lubricant level within capsules has an influence on deposition profiles and amount of drug remaining in capsule and inhaler device after actuation. It is suggested lubricant levels greater than 60 mg/kg MO per capsule are required to minimise powder retention within capsules and maximise deposition profiles. AFM (atomic force microscopy) data suggest that internal surface roughness may be related with this phenomena