Status of Precise Orbit Determination for Jason-2 Using GPS

The JASON-2 satellite, launched in June 2008, is the latest follow-on to the successful TOPEX/Poseidon (T/P) and JASON-I altimetry missions. JASON-2 is equipped with a TRSR Blackjack GPS dual-frequency receiver, a laser retroreflector array, and a DORIS receiver for precise orbit determination (POD). The most recent time series of orbits computed at NASA GSFC, based on SLR/DORIS data have been completed using both ITRF2005 and ITRF2008. These orbits have been shown to agree radially at 1 cm RMS for dynamic vs SLRlDORIS reduced-dynamic orbits and in comparison with orbits produced by other analysis centers (Lemoine et al., 2010; Zelensky et al., 2010; Cerri et al., 2010). We have recently upgraded the GEODYN software to implement model improvements for GPS processing. We describe the implementation of IGS standards to the Jason2 GEODYN GPS processing, and other dynamical and measurement model improvements. Our GPS-only JASON-2 orbit accuracy is assessed using a number of tests including analysis of independent SLR and altimeter crossover residuals, orbit overlap differences, and direct comparison to orbits generated at GSFC using SLR and DORIS tracking, and to orbits generated externally at other centers. Tests based on SLR and the altimeter crossover residuals provide the best performance indicator for independent validation of the NASAlGSFC GPS-only reduced dynamic orbits. For the ITRF2005 and ITRF2008 implementation of our GPS-only obits we are using the IGS05 and IGS08 standards. Reduced dynamic versus dynamic orbit differences are used to characterize the remaining force model error and TRF instability. We evaluate the GPS vs SLR & DORIS orbits produced using the GEODYN software and assess in particular their consistency radially and the stability of the altimeter satellite reference frame in the Z direction for both ITRF2005 and ITRF2008 as a proxy to assess the consistency of the reference frame for altimeter satellite POD

Sensitization of tumour cells to lysis by virus-specific CTL using antibody-targeted MHC class I/peptide complexes

A number of cell surface molecules with specificity to tumour cells have been identified and monoclonal antibodies (mAb) to some of these antigens have been used for targeting tumour cells in vivo. We have sought to link the powerful effector mechanisms of cytotoxic T-cells with the specificity of mAb, by targeting recombinant HLA class I molecules to tumour cells using an antibody delivery system. Soluble recombinant MHC class I/peptide complexes including HLA-A2.1 refolded around an immunodominant peptide from the HIV gag protein (HLA-A2/gag) were synthesized, and the stability of these complexes at 37°C was confirmed by enzyme-linked immunosorbent assay using a conformation-specific antibody. MHC class I-negative lymphoma cells (Daudi) were labelled with a biotinylated mAb specific for a cell surface protein (anti-CD20) then linked to soluble biotinylated HLA-A2/gag complexes using an avidin bridge. Flow cytometry revealed strong labelling of lymphoma cells with HLA-A2/gag complexes (80-fold increase in mean channel fluorescence). CTL specific for HLA-A2/gag efficiently lysed complex-targeted cells, while control CTL (specific for an HLA-A2.1-restricted epitope of melan-A) did not. Similarly, SK-mel-29 melanoma cells were also efficiently lysed by HLA-A2/gag-specific CTL when HLA-A2/gag complexes were linked to their surface via the HMW-MAA specific anti-melanoma antibody 225.28s. With further consideration to the in vivo stability of the MHC class I/peptide complexes, this system could prove a new strategy for the immunological therapy of cancer. © 2000 Cancer Research Campaig

Expression of collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of the metalloproteinases (TIMP1) in pancreatic and ampullary disease.

It is now recognised that epithelial-stromal interactions are important in a wide range of disease processes including neoplasia and inflammation. Metalloproteinases are central to matrix degradation and remodelling, which are key events in tumour invasion and metastasis and may also be involved in tissue changes occurring in chronic inflammation. Immunohistochemistry was performed on sections from 50 patients with pancreatic cancer (n = 27), ampullary cancer (n = 12), low bile duct cancer (n = 3), neuroendocrine tumours (n = 3) and chronic pancreatitis (n = 5), using antibodies raised against collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of metalloproteinase (TIMP1) and developed using the avidin-biotin complex method. Abundance of MMP2, MMP3 and TIMP1 was greater in pancreatic and ampullary cancer than any other pathology and immunoreactivity in the malignant epithelial cells in pancreatic and ampullary cancer was greater than in the stromal tissues (in pancreatic cancer: MMP2 100% vs 37%, MMP3 93% vs 15%, TIMP1 93% vs 4%, P < 0.0001). There were strong correlations between the immunoreactivity of the two antibodies for MMP2 (P < 0.0001), between MMP2 and TIMP1 (P < 0.0001) and between MMP3 and TIMP1 (P < 0.0001). The immunoreactivity for TIMP1 in pancreatic and ampullary cancers with lymph node metastases was significantly less compared with those cases without lymph node metastases (P < 0.02) and there was an association between increased immunoreactivity for MMP2 and the degree of tumour differentiation (P < 0.01). The results implicate MMP2, MMP3 and TIMP1 in the invasive phenotype of pancreatic and ampullary cancer

Spectral up- and downshifting of Akhmediev breathers under wind forcing

We experimentally and numerically investigate the effect of wind forcing on the spectral dynamics of Akhmediev breathers, a wave-type known to model the modulation instability. We develop the wind model to the same order in steepness as the higher order modifcation of the nonlinear Schroedinger equation, also referred to as the Dysthe equation. This results in an asymmetric wind term in the higher order, in addition to the leading order wind forcing term. The derived model is in good agreement with laboratory experiments within the range of the facility's length. We show that the leading order forcing term amplifies all frequencies equally and therefore induces only a broadening of the spectrum while the asymmetric higher order term in the model enhances higher frequencies more than lower ones. Thus, the latter term induces a permanent upshift of the spectral mean. On the other hand, in contrast to the direct effect of wind forcing, wind can indirectly lead to frequency downshifts, due to dissipative effects such as wave breaking, or through amplification of the intrinsic spectral asymmetry of the Dysthe equation. Furthermore, the definitions of the up- and downshift in terms of peak- and mean frequencies, that are critical to relate our work to previous results, are highlighted and discussed.Comment: 30 pages, 11 figure

Evolution of Li, Be and B in the Galaxy

In this paper we study the production of Li, Be and B nuclei by Galactic cosmic ray spallation processes. We include three kinds of processes: (i) spallation by light cosmic rays impinging on interstellar CNO nuclei (direct processes); (ii) spallation by CNO cosmic ray nuclei impinging on interstellar p and 4He (inverse processes); and (iii) alpha-alpha fusion reactions. The latter dominate the production of 6Li and 7Li. We calculate production rates for a closed-box Galactic model, verifying the quadratic dependence of the Be and B abundances for low values of Z. These are quite general results and are known to disagree with observations. We then show that the multi-zone multi-population model we used previously for other aspects of Galactic evolution produces quite good agreement with the linear trend observed at low metallicities without fine tuning. We argue that reported discrepancies between theory and observations do not represent a nucleosynthetic problem, but instead are the consequences of inaccurate treatments of Galactic evolution.Comment: 26 pages, 5 figures, LaTeX. The Astrophysical Journal, in pres

Pancreatic tumours: molecular pathways implicated in ductal cancer are involved in ampullary but not in exocrine nonductal or endocrine tumorigenesis

Alterations of K-ras, p53, p16 and DPC4/Smad4 characterize pancreatic ductal cancer (PDC). Reports of inactivation of these latter two genes in pancreatic endocrine tumours (PET) suggest that common molecular pathways are involved in the tumorigenesis of pancreatic exocrine and endocrine epithelia. We characterized 112 primary pancreatic tumours for alterations in p16 and DPC4 and immunohistochemical expression of DPC4. The cases included 34 PDC, 10 intraductal papillary-mucinous tumours (IPMT), 6 acinar carcinomas (PAC), 5 solid-pseudopapillary tumours (SPT), 16 ampulla of Vater cancers (AVC) and 41 PET. All tumours were also presently or previously analysed for K- ras and p53 mutations and allelic loss at 9p, 17p and 18q. Alterations in K- ras, p53, p16 and DPC4 were found in 82%, 53%, 38% and 9% of PDC, respectively and in 47%, 60%, 25% and 6% of AVC. Alterations in these genes were virtually absent in PET, PAC or SPT, while in IPMT only K-ras mutations were present (30%). Positive immunostaining confirmed the absence of DPC4 alterations in all IPMT, SPT, PAC and PET, while 47% of PDC and 38% of AVC were immunonegative. These data suggest that pancreatic exocrine and endocrine tumourigenesis involves different genetic targets and that among exocrine pancreatic neoplasms, only ductal and ampullary cancers share common molecular events. © 2001 Cancer Research Campaign http://www.bjcancer.co

Magnetic Fields from Phase Transitions

The generation of primordial magnetic fields from cosmological phase transitions is discussed, paying particular attention to the electroweak transition and to the various definitions of the `average' field that have been put forward. It is emphasised that only the volume average has dynamical significance as a seed for galactic dynamos. On rather general grounds of causality and energy conservation, it is shown that, in the absence of MHD effects that transfer power in the magnetic field from small to large scales, processes occurring at the electroweak transition cannot generate fields stronger than $10^{-20}$ Gauss on a scale of 0.5 Mpc. However, it is implausible that this upper bound could ever be reached, as it would require all the energy in the Universe to be turned into a magnetic field coherent at the horizon scale. Non-linear MHD effects seem therefore to be necessary if the electroweak transition is to create a primordial seed field.Comment: 6pp RevTeX. Correct finished version supplie

An effective therapeutic regime for treatment of glioma using oncolytic vaccinia virus expressing IL-21 in combination with immune checkpoint inhibition

Glioblastoma (GBM) is the most common primary malignant tumor in the brain, accounting for 51.4% of all primary brain tumors. GBM has a highly immunosuppressive tumor microenvironment (TME) and, as such, responses to immunotherapeutic strategies are poor. Vaccinia virus (VV) is an oncolytic virus that has shown tremendous therapeutic effect in various tumor types. In addition to its directly lytic effect on tumor cells, it has an ability to enhance immune cell infiltration into the TME allowing for improved immune control over the tumor. Here, we used a new generation of VV expressing the therapeutic payload interleukin-21 to treat murine GL261 glioma models. After both intratumoral and intravenous delivery, virus treatment induced remodeling of the TME to promote a robust anti-tumor immune response that resulted in control over tumor growth and long-term survival in both subcutaneous and orthotopic mouse models. Treatment efficacy was significantly improved in combination with systemic α-PD1 therapy, which is ineffective as a standalone treatment but synergizes with oncolytic VV to enhance therapeutic outcomes. Importantly, this study also revealed the upregulation of stem cell memory T cell populations after the virus treatment that exert strong and durable anti-tumor activity