Effects of prolonged acceleration with or without clinostat rotation on seedlings of Arabidopsis thaliana (L.) Heynh

Three 21-day tests of the effects of chronic centrifugation were carried out on populations of Arabidopsis thaliana. In addition to 1 g the resultant g-forces tested were: 2,4,6,8,16, and 20 g. Observed end points included gross morphological characters such as size of plant organs and, at the other extreme, features of sub-cellular structure and ultrastructure. Plants were grown on banks of clinostats. The acceleration vector was directed either parallel with the plants' axes or transverse to the axes. Plant responses to chronic axial acceleration and to transverse acceleration with clinostated plants were determined. From the data obtained it was possible in some cases: (1) to determine the g-functions of specific plant developmental characters; (2) to extrapolate those functions to the hypothetical value at zero g in order to predict (tentatively) the morphology of a plant grown in space, (3) to describe morphological effects of clinostat rotation, (4) to determine which of those effects was influenced by the prevailing g-force, and (5) to put to direct test the assumption that clinostat rotation nullifies or compensates for the influence of gravity

Application of MAC-Europe AVIRIS data to the analysis of various alteration stages in the Landdmannalauger Hydrothermal Area (South Iceland)

In June 1991 extensive airborne remote sensing data-sets have been acquired over Iceland in the framework of the joint NASA/ESA Multisensor Airborne Campaign Europe (MAC-Europe). The study area is located within the Torfajokull central volcanic complex in South Iceland. This complex is composed by anomalously abundant rhyolitic acid volcanics, which underwent intensive hydrothermal alteration. Detailed studies of surface alteration of rhyolitic rocks in the area showed that all the major elements are leached as the rock is affected by complex mineralogical changes. Montmorillonite appears during the earliest stages of alteration. In the ultimate alteration product montmorillonite is absent and the rock consists mostly of amorphous silica, anatase, up to a volume of 50% kaolinite and variable amounts of native sulphur and pyrite. The case study presented shall endeavor to assess the potential of MAC-Europe AVIRIS and TMS data in determining a possible zonation of hydrothermal alteration in relationship to the active geo-thermal fields and structural features. To this end, the airborne data is analysed in comparison with laboratory spectral measurements of characteristics rock, soil, and vegetation samples collected in the study areaduring the summer of 1992. Various spectral mapping algorithms as well as unmixing approaches are tested and evaluated. Detailed geological and structural mapping as well as geochemical analysis of the main rock and soil types were performed to underpin the analysis of the airborne data

MITF links differentiation with cell cycle arrest in melanocytes by transcriptional activation of INK4A

Cell cycle exit is required for proper differentiation in most cells and is critical for normal development, tissue homeostasis, and tumor suppression. However, the mechanisms that link cell cycle exit with differentiation remain poorly understood. Here, we show that the master melanocyte differentiation factor, microphthalmia transcription factor (MITF), regulates cell cycle exit by activating the cell cycle inhibitor INK4A, a tumor suppressor that frequently is mutated in melanomas. MITF binds the INK4A promoter, activates p16Ink4a mRNA and protein expression, and induces retinoblastoma protein hypophosphorylation, thereby triggering cell cycle arrest. This activation of INK4A was required for efficient melanocyte differentiation. Interestingly, MITF was also required for maintaining INK4A expression in mature melanocytes, creating a selective pressure to escape growth inhibition by inactivating INK4A. These findings demonstrate that INK4A can be regulated by a differentiation factor, establish a mechanistic link between melanocyte differentiation and cell cycle exit, and potentially explain the tissue-specific tendency for INK4A mutations to occur in melanoma

Polymorphic nodal elements and their application in discontinuous Galerkin methods

In this work, we discuss two different but related aspects of the development of efficient discontinuous Galerkin methods on hybrid element grids for the computational modeling of gas dynamics in complex geometries or with adapted grids. In the first part, a recursive construction of different nodal sets for hp finite elements is presented. They share the property that the nodes along the sides of the two-dimensional elements and along the edges of the three-dimensional elements are the Legendre-Gauss-Lobatto points. The different nodal elements are evaluated by computing the Lebesgue constants of the corresponding Vandermonde matrix. In the second part, these nodal elements are applied within the modal discontinuous Galerkin framework. We still use a modal based formulation, but introduce a nodal based integration technique to reduce computational cost in the spirit of pseudospectral methods. We illustrate the performance of the scheme on several large scale applications and discuss its use in a recently developed space-time expansion discontinuous Galerkin scheme. (c) 2008 Elsevier Inc. All rights reserved

Ovarian cancer molecular pathology.

Peer reviewe

Phase II study of intraperitoneal recombinant interleukin-12 (rhIL-12) in patients with peritoneal carcinomatosis (residual disease < 1 cm) associated with ovarian cancer or primary peritoneal carcinoma

<p>Abstract</p> <p>Background</p> <p>Pharmacokinetic advantages of intraperitoneal (IP) rhIL-12, tumor response to IP delivery of other cytokines as well as its potential anti-angiogenic effect provided the rationale for further evaluation of IPrhIL-12 in patients with persistent ovarian or peritoneal carcinoma.</p> <p>Methods</p> <p>A phase 2 multi-institutional trial (NCI Study #2251) of IP rIL-12 (300 nanogram/Kg weekly) was conducted in patients with ovarian carcinoma or primary peritoneal carcinoma.</p> <p>Patients treated with primary therapy for ovarian cancer who had no extraabdominal/parenchymal disease or bulky peritoneal disease were eligible. Four to 8 weeks from last chemotherapy, eligible patients underwent a laparotomy/laparoscopy. Patients with residual disease ≤ 1 cm were registered for the treatment phase 2–5 weeks post surgery. The effect of IP rIL-12 on the expression of TNFα , INFα , IL-10, IP-10, IL-8, FGF, VEGF was also studied.</p> <p>Results</p> <p>Thirty-four patients were registered for the first screening phase of the study. Median age was 56.6 years (range: 31–71); 12 completed the second phase and were evaluable for response/toxicity. Performance scores of IL-12 treated patients were 0 (11 pts) and 1 (1 pt). There were no treatment related deaths, peritonitis or significant catheter related complications. Toxicities included grade 4 neutropenia (1), grade 3 fatigue (4), headache (2), myalgia (2), non-neutropenic fever (1), drug fever (1), back pain (1), and dizziness (1). The best response observed was SD. Two patients had SD and 9 had PD, and 1 was evaluable for toxicity only.</p> <p>Peritoneal fluid cytokine measurements demonstrated a ≥ 3 fold relative increase post-rhIL-12: IFN-γ, 5/5 pts; TNF-α , 1/5; IL-10, 4/5; IL-8, 5/5; and VEGF, 3/5. IP10 levels were increased in 5/5 patients. Cytokine response profiles suggest either NK or T-cell mediated effects of IP rhIL-12. Cytokine/chemokine results also suggest a pleiotropic response since proteins with potential for either anti-tumor (IFN-γ , IP-10) or pro-tumor growth effects (VEGF, IL-8) were detected.</p> <p>Conclusion</p> <p>IP IL-12 can safely be administered at this dose and schedule to patients after first line chemotherapy for ovarian/peritoneal carcinoma. The maximum response was stable disease. Future IP therapies with rhIL-12 will require better understanding and control of pleiotropic effects of IL-12.</p

Strigolactones Negatively Regulate Mesocotyl Elongation in Rice during Germination and Growth in Darkness

Strigolactones (SLs) are newly discovered plant hormones that regulate plant growth and development including shoot branching. They also stimulate symbiosis with arbuscular mycorrhizal fungi. Rice has at least three genes that are involved in SL synthesis (D10, D17/HTD1 and D27) and at least two genes that are involved in SL signaling (D3) and SL signaling or downstream metabolism (D14/D88/HTD2). We observed that mesocotyl elongation in darkness was greater in rice mutants defective in these genes than in the wild type. Exogenous application of a synthetic SL analog, GR24, rescued the phenotype of mesocotyl elongation in the SL-deficient mutants, d10-1, d17-1 and d27-1, in a dose-dependent manner, but did not affect mesocotyl lengths of the SL-insensitive mutants, d3-1 and d14-1. No significant differences in cell length were found between the d mutants and the wild type, except for some cells on the lower half of the d3-1 mesocotyl that were shortened. On the other hand, the number of cells in the mesocotyls was 3- to 6-fold greater in the d mutants than in the wild type. Treatment with GR24 reduced the number of cells in the d10-1 mesocotyl to the wild-type level, but did not affect the number of cells in the d3-1 and d14-1 mesocotyls. These findings indicate that SLs negatively regulate cell division, but not cell elongation, in the mesocotyl during germination and growth of rice in darkness

Overexpression of the Axl tyrosine kinase receptor in cutaneous SCC-derived cell lines and tumours

The molecular mechanisms that underlie the development of squamous cell skin cancers (SSC) are poorly understood. We have used oligonucleotide microarrays to compare the differences in cellular gene expression between a series of keratinocyte cell that mimic disease progression with the aim of identifying genes that may potentially contribute towards squamous cell carcinoma (SCC) progression in vivo, and in particular to identify markers that may serve as potential therapeutic targets for SCC treatment. Gene expression differences were corroborated by polymerase chain reaction and Western blotting. We identified Axl, a receptor tyrosine kinase with transforming potential that has also been shown to have a role in cell survival, adhesion and chemotaxis, was upregulated in vitro in SCC-derived cells compared to premalignant cells. Extending the investigation to tumour biopsies showed that the Axl protein was overexpressed in vivo in a series of SCCs