Implications of Shock Wave Experiments with Precompressed Materials for Giant Planet Interiors

This work uses density functional molecular dynamics simulations of fluid helium at high pressure to examine how shock wave experiments with precompressed samples can help characterizing the interior of giant planets. In particular, we analyze how large of a precompression is needed to probe a certain depth in a planet's gas envelope. We find that precompressions of up to 0.1, 1.0, 10, or 100 GPa are needed to characterized 2.5, 5.9, 18, to 63% of Jupiter's envelope by mass.Comment: Submitted As Proceedings Article For The American Physical Society Meeting On Shock Compression Of Condensed Matter, Hawaii, June, 200

Tissue transglutaminase treatment leads to concentration-dependent changes in dendritic cell phenotype--implications for the role of transglutaminase in coeliac disease.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Dendritic cells (DCs) are part of the innate immune system with a key role in initiating and modulating T cell mediated immune responses. Coeliac disease is caused by inappropriate activation of such a response leading to small intestinal inflammation when gluten is ingested. Tissue transglutaminase, an extracellular matrix (ECM) protein, has an established role in coeliac disease; however, little work to date has examined its impact on DCs. The aim of this study was to investigate the effect of small intestinal ECM proteins, fibronectin (FN) and tissue transglutaminase 2 (TG-2), on human DCs by including these proteins in DC cultures.The study used flow cytometry and scanning electron microscopy to determine the effect of FN and TG-2 on phenotype, endocytic ability and and morphology of DCs. Furthermore, DCs treated with FN and TG-2 were cultured with T cells and subsequent T cell proliferation and cytokine profile was determined.The data indicate that transglutaminase affected DCs in a concentration-dependent manner. High concentrations were associated with a more mature phenotype and increased ability to stimulate T cells, while lower concentrations led to maintenance of an immature phenotype.These data provide support for an additional role for transglutaminase in coeliac disease and demonstrate the potential of in vitro modelling of coeliac disease pathogenesis.Published versio

In Vivo screening and discovery of novel candidate thalidomide analogs in the zebrafish embryo and chicken embryo model systems

This study was supported by a Wellcome Trust-NIH PhD Studentship to SB, WDF and NV. Grant number 098252/Z/12/Z. SB, CHC and WDF are supported by the Intramural Research Program, NCI, NIH. NHG and WL are supported by the Intramural Research Program, NIA, NIH.Peer reviewedPublisher PD

Project Antares: A low cost modular launch vehicle for the future

The single stage to orbit launch vehicle Antares is based upon the revolutionary concept of modularity, enabling the Antares to efficiently launch communications satellites, as well as heavy payloads, into Earth's orbit and beyond. The basic unit of the modular system, a single Antares vehicle, is aimed at launching approximately 10,000 kg into low Earth orbit (LEO). When coupled with a Centaur upper stage it is capable of placing 3500 kg into geostationary orbit. The Antares incorporates a reusable engine, the Dual Mixture Ratio Engine (DMRE), as its propulsive device. This enables Antares to compete and excel in the satellite launch market by dramatically reducing launch costs. Antares' projected launch costs are $1340 per kg to LEO which offers a tremendous savings over launch vehicles available today. Inherent in the design is the capability to attach several of these vehicles together to provide heavy lift capability. Any number of these vehicles, up to seven, can be attached depending on the payload and mission requirements. With a seven vehicle configuration Antares's modular concept provides a heavy lift capability of approximately 70,000 kg to LEO. This expandability allows for a wider range of payload options such as large Earth satellites, Space Station Freedom support, and interplanetary spacecraft, and also offers a significant cost savings over a mixed fleet based on different launch vehicles

Overcoming Resistance to Immunotherapy in Head and Neck Cancer Using Radiation: A Review.

Radiation therapy remains at the center of head and neck cancer treatment. With improvements in treatment delivery, radiation therapy has become an affective ablative modality for head and neck cancers. Immune checkpoint inhibitors are now also playing a more active role both in the locally advanced and metastatic setting. With improved systemic options, local noninvasive modalities including radiation therapy are playing a critical role in overcoming resistance in head and neck cancer. The aim of this review is to describe the role of radiation therapy in modulating the tumor microenvironment and how radiation dose, fractionation and treatment field can impact the immune system and potentially effect outcomes when combined with immunotherapy. The review will encompass several common scenarios where radiation is used to improve outcomes and overcome potential resistance that may develop with immunotherapy in head and neck squamous cell carcinoma (HNSCC), including upfront locally advanced disease receiving definitive radiation and recurrent disease undergoing re-irradiation. Lastly, we will review the potential toxicities of combined therapy and future directions of their role in the management of HNSCC

Shared mechanism of teratogenicity of anti-angiogenic drugs identified in the chicken embryo model

Acknowledgements The authors would like to thank Maria Kisakyamaria and Scott McMenemy for preliminary experimental data. This work was supported by a Wellcome Trust-NIH PhD Studentship awarded to SB, WDF and NV (Grant number 098252/Z/12/Z). This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government.Peer reviewedPublisher PD

Comparing the effectiveness of TAT and myristoylation of gp91ds on leukocyte superoxide (SO) release

It is well known that adding myristic acid or transactivating (TAT)carrier peptide to native peptides will facilitate cell membranepermeability required for targeting intracellular substrates. However, it is not known if differences exist in the effectiveness of myristic acid versus TAT conjugated peptides. To test this, we compared the dose-response relationship of myristoylated (Myr-peg linker-C-S-TR-I-R-R-Q-L-NH2oxidase assembly inhibitor (gp91ds), ([H]-R-K-K-R-R-Q-R-R-R- CS-T-R-I-R-R-Q-L-NH2gp91ds with glycine-glycine spacer in between TAT and gp91ds (MW=2566 g/mol) on N-Formyl-L-Methionyl-L-Leucyl-L-Phenylalanine (fMLP) induced leukocyte superoxide (SO) release.Myr-peg-gp91ds NADPH oxidase peptide inhibitor significantly attenuated fMLP-induced leukocyte SO release dose dependently (40±11%; 2 μM; n=13), (53±8%; 5μM; n=13), and (64±8%;10μM; n=11, p\u3c0.01) compared to fMLP (1μM; n= 29; change in absorbance 0.196±0.012 from baseline) or native sequence which inhibited the fMLP response by only 11±4% at the highest dose tested (80μM; n=10). The TAT gp91ds inhibitors (both 80μM; n=13, p\u3c0.05) significantly attenuated fMLP-induced leukocyte SO release by 35±11%, but to a lesser extent than the myr-peg linked inhibitor. These results suggest that myr-peg-gp91ds is more cell permeable and therefore can inhibit fMLP-induced SO release from leukocytes at lower doses compared to TAT gp91ds.; MW=1486 g/mol) and TAT conjugated NADPH ; MW=2452 g/mol) or TAT conjugated