Selective cancer cell killing by α-tocopheryl succinate

We report that α-tocopheryl succinate, a vitamin E analogue with pro-apoptotic properties, selectively kills cells with a malignant or transformed phenotype, i.e. multiple haematopoietic and carcinoma cell lines, while being non-toxic to normal, i.e. primary and non-transformed cells. These findings strongly suggest a potential of this micronutrient in the therapy and/or prevention of cancer without significant side-effects. © 2001 Cancer Research Campaign http://www.bjcancer.co

Bio-inspired Composite Hydrogels for Osteochondral Regenerative Engineering

Treatment of osteochondral defects encompassing injury or degeneration to both the articular cartilage as well as the underlying subchondral bone presents a significant medical challenge. Current treatment options including autografts and allografts suffer from limited availability and risk of immunogenicity, respectively. The long term goal of this work is to develop an integrated scaffold system for treatment of osteochondral defects via in situ regeneration of bone, cartilage and the bone-cartilage interface. Hydrogels composed of polymer networks swollen in water provide an attractive biomaterial platform for regeneration of cartilage. In the present study, we have developed a novel composite hydrogel consisting of thiolated hyaluronic acid (HA) and chondroitin sulfate (CS) crosslinked with polyethylene glycol (PEG). The combination of HA and CS offers a biomimetic microenvironment found in cartilage whereas the selection of PEG as a crosslinker is based on its established biocompatibility and chemical versatility. Variations in the crosslinking density enable the ability to fine-tune physical properties of hydrogels. For example, the rheology tests of different hydrogels with increased crosslinking densities showed an increase in equilibrium gel modulus. In vitro study with human mesenchymal stem cells (hMSCs) demonstrated the ability of the hydrogel to support three-dimensional cell encapsulation with high viability. Interestingly, increased crosslinking also promoted phosphorylation of focal adhesion kinase, a potential early mechanosensor that respond to changes in mechanical stiffness. Future in vitro and in vivo studies will be performed to optimize the hydrogels for chondrogenic cellular responses and osteochondral regeneration

Evolution of Harmonic Distortion in a Cablified Grid Island after Separation from the Meshed Transmission Grid - A Case Study from Denmark

Green transition in Denmark with more renewable energy production and electrification of consumption, transport, heating, energy conversion and storage accelerates expansion and reconstruction of the transmission grid. When electricity generation and consumption have common connection cables and substations in the transmission grid, such centres are called prosumers.The prosumers do not necessarily increase the net energy exchange with the transmission grid but their short-circuit current contribution may significantly increase due to utilization of inverter-based units. To keep the short-circuit current contribution below the required rating, the meshed 150 kV transmission grid will be separated into islands that are interconnected through the 400 kV meshed transmission system. At the same time, 150 kV overhead lines will be replaced with underground cables as part of the ongoing grid reconstruction in Denmark. This paper presents the simulation results of the 5th harmonic voltage distortion evolution from the present grid stage with the meshed 150 kV transmission grid and, mainly, with overhead lines, through a long-term grid development process with cabling and separation of the meshed grid into 150 kV grid islands. The paper explains foreseen changes of the 5th harmonic voltage distortion within a specific grid island using a measurement validated simulation model for harmonic assessment and benchmarking the simulation results to the harmonic voltage measurements in the present grid stage. The paper also demonstrates identification and usage of early warnings for not-yet-occurred critical increases of the harmonic voltage distortion and proposal of mitigation solutions.<br/

The Impact of Java Applications at Microarchitectural Level from Branch Prediction Perspective

The portability, the object-oriented and distributed programming models, multithreading support and automatic garbage collection are features that make Java very attractive for application developers. The main goal of this paper consists in pointing out the impact of Java applications at microarchitectural level from two perspectives: unbiased branches and indirect jumps/calls, such branches limiting the ceiling of dynamic branch prediction and causing significant performance degradation. Therefore, accurately predicting this kind of branches remains an open problem. The simulation part of the paper mainly refers to determining the context length influence on the percentage of unbiased branches from Java applications, the prediction accuracy and the usage degree obtained using a Fast Path-Based Perceptron predictor. We realize a comparison with C/C++ application behavior from unbiased branches perspective. We also analyze some Java testing programs, built using design patterns or including inheritance, polymorphism, backtracking and recursivity, in order to determine the features of indirect branches, the arity of each indirect jump and the prediction accuracy using the Target Cache predictor

Normalized Affymetrix expression data are biased by G-quadruplex formation

Probes with runs of four or more guanines (G-stacks) in their sequences can exhibit a level of hybridization that is unrelated to the expression levels of the mRNA that they are intended to measure. This is most likely caused by the formation of G-quadruplexes, where inter-probe guanines form Hoogsteen hydrogen bonds, which probes with G-stacks are capable of forming. We demonstrate that for a specific microarray data set using the Human HG-U133A Affymetrix GeneChip and RMA normalization there is significant bias in the expression levels, the fold change and the correlations between expression levels. These effects grow more pronounced as the number of G-stack probes in a probe set increases. Approximately 14 of the probe sets are directly affected. The analysis was repeated for a number of other normalization pipelines and two, FARMS and PLIER, minimized the bias to some extent. We estimate that ∼15 of the data sets deposited in the GEO database are susceptible to the effect. The inclusion of G-stack probes in the affected data sets can bias key parameters used in the selection and clustering of genes. The elimination of these probes from any analysis in such affected data sets outweighs the increase of noise in the signal. © 2011 The Author(s)

Retrieval of Compositional Endmembers from Mars Exploration Rover Opportunity Observations in a Soil-filled Fracture in Marathon Valley, Endeavour Crater Rim

The Opportunity rover investigated a gentle swale on the rim of Endeavour crater called Marathon Valley where a series of bright planar outcrops are cut into polygons by fractures. A wheel scuff performed on one of the soil-filled fracture zones revealed the presence of three end-members identified on the basis of Pancam multispectral imaging observations covering ~0.4 to 1 μm: red and dark pebbles, and a bright soil clod. Multiple overlapping Alpha Particle X-ray Spectrometer (APXS) measurements were collected on three targets within the scuff zone. The field of view of each APXS measurement contained various proportions of the Pancam-based end-members. Application of a log maximum likelihood method for retrieving the composition of the end-members using the 10 APXS measurements shows that the dark pebble end-member is compositionally similar to average Mars soil, with slightly elevated S and Fe. In contrast, the red pebble end-member exhibits enrichments in Al and Si and is depleted in Fe and Mg relative to average Mars soil. The soil clod end-member is enriched in Mg, S, and Ni. Thermodynamic modeling of the soil clod end-member composition indicates a dominance of sulfate minerals. We hypothesize that acidic fluids in fractures leached and oxidized the basaltic host rock, forming the red pebbles, and then evaporated to leave behind sulfate-cemented soil

Retrieval of Compositional End-Members From Mars Exploration Rover Opportunity Observations in a Soil-Filled Fracture in Marathon Valley, Endeavour Crater Rim

The Opportunity rover investigated a gentle swale on the rim of Endeavour crater called Marathon Valley where a series of bright planar outcrops are cut into polygons by fractures. A wheel scuff performed on one of the soil‐filled fracture zones revealed the presence of three end‐members identified on the basis of Pancam multispectral imaging observations covering ~0.4 to 1 μm: red and dark pebbles, and a bright soil clod. Multiple overlapping Alpha Particle X‐ray Spectrometer (APXS) measurements were collected on three targets within the scuff zone. The field of view of each APXS measurement contained various proportions of the Pancam‐based end‐members. Application of a log maximum likelihood method for retrieving the composition of the end‐members using the 10 APXS measurements shows that the dark pebble end‐member is compositionally similar to average Mars soil, with slightly elevated S and Fe. In contrast, the red pebble end‐member exhibits enrichments in Al and Si and is depleted in Fe and Mg relative to average Mars soil. The soil clod end‐member is enriched in Mg, S, and Ni. Thermodynamic modeling of the soil clod end‐member composition indicates a dominance of sulfate minerals. We hypothesize that acidic fluids in fractures leached and oxidized the basaltic host rock, forming the red pebbles, and then evaporated to leave behind sulfate‐cemented soil

Sulfate Deposition in Regolith Exposed in Trenches on the Plains Between the Spirit Landing Site and Columbia Hills in Gusev Crater, Mars

During its exploration within Gusev crater between sol 01 and sol 158, the Spirit rover dug three trenches (Fig. 1) to expose the subsurface regolith [1, 2, 9]. Laguna trench (approx. 6 cm deep, approx.203 m from the rim of Bonneville crater) was dug in Laguna Hollow at the boundary of the impact ejecta from Bonneville crater and the surrounding plains. The Big Hole trench (approx. 6-7 cm deep) and The Boroughs trench (approx. 11 cm deep) were dug in the plains between the Bonneville crater and the Columbia Hills (approx.556 m and approx.1698 m from the rim of Bonneville crater respectively). The top, wall and floor regolith of the three trenches were investigated using the entire set of Athena scientific instruments [10]

Transport properties of the azimuthal magnetorotational instability

The magnetorotational instability (MRI) is thought to be a powerful source of turbulence in Keplerian accretion disks. Motivated by recent laboratory experiments, we study the MRI driven by an azimuthal magnetic field in an electrically conducting fluid sheared between two concentric rotating cylinders. By adjusting the rotation rates of the cylinders, we approximate angular velocity profiles ω ∝ r q . We perform direct numerical simulations of a steep profile close to the Rayleigh line q & −2 and a quasiKeplerian profile q ≈ −3/2 and cover wide ranges of Reynolds (Re ≤ 4 · 104 ) and magnetic Prandtl numbers (0 ≤ Pm ≤ 1). In the quasi-Keplerian case, the onset of instability depends on the magnetic Reynolds number, with Rmc ≈ 50, and angular momentum transport scales as √ PmRe2 in the turbulent regime. The ratio of Maxwell to Reynolds stresses is set by Rm. At the onset of instability both stresses have similar magnitude, whereas the Reynolds stress vanishes or becomes even negative as Rm increases. For the profile close to the Rayleigh line, the instability shares these properties as long as Pm & 0.1, but exhibits a markedly different character if Pm → 0, where the onset of instability is governed by the Reynolds number, with Rec ≈ 1250, transport is via Reynolds stresses and scales as Re2 . At intermediate Pm = 0.01 we observe a continuous transition from one regime to the other, with a crossover at Rm = O(100). Our results give a comprehensive picture of angular momentum transport of the MRI with an imposed azimuthal field