Primordial magnetic fields at preheating

Using lattice techniques we investigate the generation of long range cosmological magnetic fields during a cold electroweak transition. We will show how magnetic fields arise, during bubble collisions, in the form of magnetic strings. We conjecture that these magnetic strings originate from the alignment of magnetic dipoles associated with EW sphaleron-like configurations. We also discuss the early thermalisation of photons and the turbulent behaviour of the scalar fields after tachyonic preheating.Comment: 7 pages. Talk presented at Lattice200

ALMA Observations of Supernova Remnant N49 in the LMC. I. Discovery of CO Clumps Associated with X-Ray and Radio Continuum Shells

N49 (LHA 120-N49) is a bright X-ray supernova remnant (SNR) in the Large Magellanic Cloud. We present new 12CO (J = 1–0, 3–2), H i, and 1.4 GHz radio continuum observations of the SNR N49 using Mopra, ASTE, ALMA, and ATCA. We have newly identified three H i clouds using ATCA with an angular resolution of ~20'': one associated with the SNR and the others located in front of the SNR. Both the CO and H i clouds in the velocity range from 281 to 291 km s−1 are spatially correlated with both the soft X-rays (0.2–1.2 keV) and the hard X-rays (2.0–7.0 keV) of N49 on a ~10 pc scale. CO 3–2/1–0 intensity ratios indicate higher values of the CO cloud toward the SNR shell with an angular resolution of ~45'', and thus a strong interaction was suggested. Using the ALMA, we have spatially resolved CO clumps embedded within or along the southeastern rim of N49 with an angular resolution of ~3''. Three of the CO clumps are rim brightened on a 0.7–2 pc scale in both hard X-rays and the radio continuum: this provides further evidence for dynamical interactions between the CO clumps and the SNR shock wave. The enhancement of the radio synchrotron radiation can be understood in terms of magnetic field amplification around the CO clumps via a shock–cloud interaction. We also present a possible scenario in which the recombining plasma that dominates the hard X-rays from N49 was formed via thermal conduction between the SNR shock waves and the cold/dense molecular clumps

JACIE accreditation for blood and marrow transplantation: past, present and future directions of an international model for healthcare quality improvement.

Blood and marrow transplantation (BMT) is a complex and evolving medical speciality that makes substantial demands on healthcare resources. To meet a professional responsibility to both patients and public health services, the European Society for Blood and Marrow Transplantation (EBMT) initiated and developed the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT-better known by the acronym, JACIE. Since its inception, JACIE has performed over 530 voluntary accreditation inspections (62% first time; 38% reaccreditation) in 25 countries, representing 40% of transplant centres in Europe. As well as widespread professional acceptance, JACIE has become incorporated into the regulatory framework for delivery of BMT and other haematopoietic cellular therapies in several countries. In recent years, JACIE has been validated using the EBMT registry as an effective means of quality improvement with a substantial positive impact on survival outcomes. Future directions include development of Europe-wide risk-adjusted outcome benchmarking through the EBMT registry and further extension beyond Europe, including goals to faciliate access for BMT programmes in in low- and middle-income economies (LMIEs) via a 'first-step' process

Accelerated high-dose radiotherapy alone or combined with either concomitant or sequential chemotherapy; treatments of choice in patients with Non-Small Cell Lung Cancer

<p>Abstract</p> <p>Background</p> <p>Results of high-dose chemo-radiotherapy (CRT), using the treatment schedules of EORTC study 08972/22973 or radiotherapy (RT) alone were analyzed among all patients (pts) with Non Small Cell Lung Cancer (NSCLC) treated with curative intent in our department from 1995–2004.</p> <p>Material</p> <p>Included are 131 pts with medically inoperable or with irresectable NSCLC (TNM stage I:15 pts, IIB:15 pts, IIIA:57 pts, IIIB:43 pts, X:1 pt).</p> <p>Treatment</p> <p>Group I: Concomitant CRT: 66 Gy/2.75 Gy/24 fractions (fx)/33 days combined with daily administration of cisplatin 6 mg/m²: 56 pts (standard).</p> <p>Group II: Sequential CRT: two courses of a 21-day schedule of chemotherapy (gemcitabin 1250 mg/m²d1, cisplatin 75 mg/m2 d2) followed by 66 Gy/2.75 Gy/24 fx/33 days without daily cisplatin: 26 pts.</p> <p>Group III: RT: 66 Gy/2.75 Gy/24 fx/33 days or 60 Gy/3 Gy/20 fx/26 days: 49 pts.</p> <p>Results</p> <p>The 1, 2, and 5 year actuarial overall survival (OS) were 46%, 24%, and 15%, respectively.</p> <p>At multivariate analysis the only factor with a significantly positive influence on OS was treatment with chemo-radiation (P = 0.024) (1-, 2-, and 5-yr OS 56%, 30% and 22% respectively). The incidence of local recurrence was 36%, the incidence of distant metastases 46%.</p> <p>Late complications grade 3 were seen in 21 pts and grade 4 in 4 patients. One patient had a lethal complication (oesophageal). For 32 patients insufficient data were available to assess late complications.</p> <p>Conclusion</p> <p>In this study we were able to reproduce the results of EORTC trial 08972/22973 in a non-selected patient population outside of the setting of a randomised trial. Radiotherapy (66 Gy/24 fx/33 days) combined with either concomitant daily low dose cisplatin or with two neo-adjuvant courses of gemcitabin and cisplatin are effective treatments for patients with locally advanced Non-Small Cell Lung Cancer. The concomitant schedule is also suitable for elderly people with co-morbidity.</p

The conserved dileucine- and tyrosine-based motifs in MLV and MPMV envelope glycoproteins are both important to regulate a common Env intracellular trafficking

BACKGROUND: Retrovirus particles emerge from the assembly of two structural protein components, Gag that is translated as a soluble protein in the cytoplasm of the host cells, and Env, a type I transmembrane protein. Because both components are translated in different intracellular compartments, elucidating the mechanisms of retrovirus assembly thus requires the study of their intracellular trafficking. RESULTS: We used a CD25 (Tac) chimera-based approach to study the trafficking of Moloney murine leukemia virus and Mason-Pfizer monkey virus Env proteins. We found that the cytoplasmic tails (CTs) of both Env conserved two major signals that control a complex intracellular trafficking. A dileucine-based motif controls the sorting of the chimeras from the trans-Golgi network (TGN) toward endosomal compartments. Env proteins then follow a retrograde transport to the TGN due to the action of a tyrosine-based motif. Mutation of either motif induces the mis-localization of the chimeric proteins and both motifs are found to mediate interactions of the viral CTs with clathrin adaptors. CONCLUSION: This data reveals the unexpected complexity of the intracellular trafficking of retrovirus Env proteins that cycle between the TGN and endosomes. Given that Gag proteins hijack endosomal host proteins, our work suggests that the endosomal pathway may be used by retroviruses to ensure proper encountering of viral structural Gag and Env proteins in cells, an essential step of virus assembly

Prenylation Inhibition-Induced Cell Death in Melanoma: Reduced Sensitivity in BRAF Mutant/PTEN Wild-Type Melanoma Cells.

While targeted therapy brought a new era in the treatment of BRAF mutant melanoma, therapeutic options for non-BRAF mutant cases are still limited. In order to explore the antitumor activity of prenylation inhibition we investigated the response to zoledronic acid treatment in thirteen human melanoma cell lines with known BRAF, NRAS and PTEN mutational status. Effect of zoledronic acid on proliferation, clonogenic potential, apoptosis and migration of melanoma cells as well as the activation of downstream elements of the RAS/RAF pathway were investigated in vitro with SRB, TUNEL and PARP cleavage assays and videomicroscopy and immunoblot measurements, respectively. Subcutaneous and spleen-to-liver colonization xenograft mouse models were used to evaluate the influence of zoledronic acid treatment on primary and disseminated tumor growth of melanoma cells in vivo. Zoledronic acid more efficiently decreased short-term in vitro viability in NRAS mutant cells when compared to BRAF mutant and BRAF/NRAS wild-type cells. In line with this finding, following treatment decreased activation of ribosomal protein S6 was found in NRAS mutant cells. Zoledronic acid demonstrated no significant synergism in cell viability inhibition or apoptosis induction with cisplatin or DTIC treatment in vitro. Importantly, zoledronic acid could inhibit clonogenic growth in the majority of melanoma cell lines except in the three BRAF mutant but PTEN wild-type melanoma lines. A similar pattern was observed in apoptosis induction experiments. In vivo zoledronic acid did not inhibit the subcutaneous growth or spleen-to-liver colonization of melanoma cells. Altogether our data demonstrates that prenylation inhibition may be a novel therapeutic approach in NRAS mutant melanoma. Nevertheless, we also demonstrated that therapeutic sensitivity might be influenced by the PTEN status of BRAF mutant melanoma cells. However, further investigations are needed to identify drugs that have appropriate pharmacological properties to efficiently target prenylation in melanoma cells

Murchison Widefield Array and XMM-Newton observations of the Galactic supernova remnant G5.9+3.1

Aims. In this paper we discuss the radio continuum and X-ray properties of the so-far poorly studied Galactic supernova remnant (SNR) G5.9 + 3.1. Methods. We present the radio spectral energy distribution (SED) of the Galactic SNR G5.9 + 3.1 obtained with the Murchison Widefield Array (MWA). Combining these new observations with the surveys at other radio continuum frequencies, we discuss the integrated radio continuum spectrum of this particular remnant. We have also analyzed an archival XMM-Newton observation, which represents the first detection of X-ray emission from this remnant. Results. The SNR SED is very well explained by a simple power-law relation. The synchrotron radio spectral index of G5.9 + 3.1 is estimated to be 0.42 ± 0.03 and the integrated flux density at 1 GHz to be around 2.7 Jy. Furthermore, we propose that the identified point radio source, located centrally inside the SNR shell, is most probably a compact remnant of the supernova explosion. The shell-like X-ray morphology of G5.9 + 3.1 as revealed by XMM-Newton broadly matches the spatial distribution of the radio emission, where the radio-bright eastern and western rims are also readily detected in the X-ray while the radio-weak northern and southern rims are weak or absent in the X-ray. Extracted MOS1+MOS2+PN spectra from the whole SNR as well as the north, east, and west rims of the SNR are fit successfully with an optically thin thermal plasma model in collisional ionization equilibrium with a column density NH ~ 0.80 × 1022 cm−2 and fitted temperatures spanning the range kT ~ 0.14–0.23 keV for all of the regions. The derived electron number densities ne for the whole SNR and the rims are also roughly comparable (ranging from ~0.20f−1∕2 to ~0.40f−1∕2 cm−3, where f is the volume filling factor). We also estimate the swept-up mass of the X-ray emitting plasma associated with G5.9+3.1 to be ~46f−1∕2 M⊙.</jats:p