Epidermal growth factor receptor variant III mediates head and neck cancer cell invasion via STAT3 activation.

Epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) where aberrant signaling downstream of this receptor contributes to tumor growth. EGFR variant III (EGFRvIII) is the most commonly altered form of EGFR and contains a truncated ligand-binding domain. We previously reported that EGFRvIII is expressed in up to 40% of HNSCC tumors where it is associated with increased proliferation, tumor growth and chemoresistance to antitumor drugs including the EGFR-targeting monoclonal antibody cetuximab. Cetuximab was FDA-approved in 2006 for HNSCC but has not been shown to prevent invasion or metastasis. This study was undertaken to evaluate the mechanisms of EGFRvIII-mediated cell motility and invasion in HNSCC. We found that EGFRvIII induced HNSCC cell migration and invasion in conjunction with increased signal transducer and activator of transcription 3 (STAT3) activation, which was not abrogated by cetuximab treatment. Further investigation showed that EGF-induced expression of the STAT3 target gene HIF1-α, was abolished by cetuximab in HNSCC cells expressing wild-type EGFR under hypoxic conditions, but not in EGFRvIII-expressing HNSCC cells. These results suggest that EGFRvIII mediates HNSCC cell migration and invasion by increased STAT3 activation and induction of HIF1-α, which contribute to cetuximab resistance in EGFRvIII-expressing HNSCC tumors

Optimization of moisture content for wheat seedling germination in a cellulose acetate medium for a space flight experiment

The Porous Tube Plant Nutrient Delivery System (PTPNDS), a hydrophilic, microporous ceramic tube hydroponic system designed for microgravity, will be tested in a middeck locker of the Space Shuttle. The flight experiment will focus on hardware operation and assess its ability to support seed germination and early seedling growth in microgravity. The water controlling system of the PTPNDS hardware has been successfully tested during the parabolic flight of the KC-135. One challenge to the development of the spaceflight experiment was to devise a method of holding seeds to the cylindrical porous tube. The seed holder must provide water and air to the seed, absorb water from the porous tube, withstand sterilization, provide a clear path for shoots and roots to emerge, and be composed of flight qualified materials. In preparation for the flight experiment, a wheat seed-holder has been designed that utilizes a cellulose acetate plug to facilitate imbibition and to hold the wheat seeds in contact with the porous tube in the correct orientation during the vibration of launch and the microgravity environment of orbit. Germination and growth studies with wheat at a range of temperatures showed that optimal moisture was 78% (by weight) in the cellulose acetate seed holders. These and other design considerations are discussed

Physical realization of a quantum spin liquid based on a novel frustration mechanism

Unlike conventional magnets where the magnetic moments are partially or completely static in the ground state, in a quantum spin liquid they remain in collective motion down to the lowest temperatures. The importance of this state is that it is coherent and highly entangled without breaking local symmetries. Such phenomena is usually sought in simple lattices where antiferromagnetic interactions and/or anisotropies that favor specific alignments of the magnetic moments are "frustrated" by lattice geometries incompatible with such order e.g. triangular structures. Despite an extensive search among such compounds, experimental realizations remain very few. Here we describe the investigation of a novel, unexplored magnetic system consisting of strong ferromagnetic and weaker antiferromagnetic isotropic interactions as realized by the compound Ca$_{10}$Cr$_7$O$_{28}$. Despite its exotic structure we show both experimentally and theoretically that it displays all the features expected of a quantum spin liquid including coherent spin dynamics in the ground state and the complete absence of static magnetism.Comment: Modified version accepted in Nature Physic

Mitochondrial phylogeography and demographic history of the Vicuña: implications for conservation

The vicuña (Vicugna vicugna; Miller, 1924) is a conservation success story, having recovered from near extinction in the 1960s to current population levels estimated at 275 000. However, lack of information about its demographic history and genetic diversity has limited both our understanding of its recovery and the development of science-based conservation measures. To examine the evolution and recent demographic history of the vicuña across its current range and to assess its genetic variation and population structure, we sequenced mitochondrial DNA from the control region (CR) for 261 individuals from 29 populations across Peru, Chile and Argentina. Our results suggest that populations currently designated as Vicugna vicugna vicugna and Vicugna vicugna mensalis comprise separate mitochondrial lineages. The current population distribution appears to be the result of a recent demographic expansion associated with the last major glacial event of the Pleistocene in the northern (18 to 22°S) dry Andes 14–12 000 years ago and the establishment of an extremely arid belt known as the 'Dry Diagonal' to 29°S. Within the Dry Diagonal, small populations of V. v. vicugna appear to have survived showing the genetic signature of demographic isolation, whereas to the north V. v. mensalis populations underwent a rapid demographic expansion before recent anthropogenic impacts

Adding flexibility to clinical trial designs: an example-based guide to the practical use of adaptive designs.

Funder: Cancer Research UK; doi: http://dx.doi.org/10.13039/501100000289Adaptive designs for clinical trials permit alterations to a study in response to accumulating data in order to make trials more flexible, ethical, and efficient. These benefits are achieved while preserving the integrity and validity of the trial, through the pre-specification and proper adjustment for the possible alterations during the course of the trial. Despite much research in the statistical literature highlighting the potential advantages of adaptive designs over traditional fixed designs, the uptake of such methods in clinical research has been slow. One major reason for this is that different adaptations to trial designs, as well as their advantages and limitations, remain unfamiliar to large parts of the clinical community. The aim of this paper is to clarify where adaptive designs can be used to address specific questions of scientific interest; we introduce the main features of adaptive designs and commonly used terminology, highlighting their utility and pitfalls, and illustrate their use through case studies of adaptive trials ranging from early-phase dose escalation to confirmatory phase III studies

Dwarf Tomato and Pepper Cultivars for Space Crops

Several dwarf tomato and pepper varieties were evaluated under ISS-simulated growth conditions (22C, 50% RH, 1500 ppm CO2, and 300 mol m(exp -2) s(exp -1) of light for 16 h per day) with the goal of selecting those with the best growth, nutrition, and organoleptic potential for use in a pick and eat salad crop system on ISS and future exploration flights. Testing included six cultivars of tomato (Red Robin, Scarlet Sweet N Neat, Tiny Tim, Mohamed, Patio Princess, and Tumbler) and six cultivars of pepper (Red Skin, Fruit Basket, Cajun Belle, Chablis, Sweet Pickle, and Pompeii). Plants were grown to an age sufficient to produce fruit (70 to 106 days for tomato and 109 days for pepper). Tomato fruits were harvested when they showed full red color, beginning ca. 70-days age and then at weekly intervals thereafter, while peppers were grown until numerous fruits showed color and all fruits (green and colored) were harvested once at the end of the test. Plant sizes, yields, and nutritional attributes were measured and used to down-select to three cultivars for each species. In particular, we were interested in cultivars that were short (dwarf) but still produced high yields. Nutritional data included elemental (Ca, Mg, Fe, and K) composition, vitamin K, phenolics, lycopene, anthocyanin, lutein, and zeaxanthin. The three down-selected cultivars for each species were evaluated for sensory attributes, including overall acceptability, appearance, color intensity aroma, flavor and texture. The combined data were compared and given weighting factors to rank the cultivars as potential candidates for testing in space. For tomato, the ranking was 1) cv. Mohamed, 2) cv. Red Robin, and 3) cv. Sweet N Neat. For pepper, the ranking was 1) cv. Pompeii, 2) cv. Red Skin, and 3) cv. Fruit Basket. These rankings are somewhat subjective but provide a good starting point for conducting higher fidelity testing with these crops (e.g., testing with LED lighting similar to the Veggie plant unit), and ultimately conducting flight experiments

Deterministic models of quantum fields

Deterministic dynamical models are discussed which can be described in quantum mechanical terms. -- In particular, a local quantum field theory is presented which is a supersymmetric classical model. The Hilbert space approach of Koopman and von Neumann is used to study the classical evolution of an ensemble of such systems. Its Liouville operator is decomposed into two contributions, with positive and negative spectrum, respectively. The unstable negative part is eliminated by a constraint on physical states, which is invariant under the Hamiltonian flow. Thus, choosing suitable variables, the classical Liouville equation becomes a functional Schroedinger equation of a genuine quantum field theory. -- We briefly mention an U(1) gauge theory with ``varying alpha'' or dilaton coupling where a corresponding quantized theory emerges in the phase space approach. It is energy-parity symmetric and, therefore, a prototype of a model in which the cosmological constant is protected by a symmetry.Comment: 6 pages; synopsis of hep-th/0510267, hep-th/0503069, hep-th/0411176 . Talk at Constrained Dynamics and Quantum Gravity - QG05, Cala Gonone (Sardinia, Italy), September 12-16, 2005. To appear in the proceeding