Limit on suppression of ionization in metastable neon traps due to long-range anisotropy

This paper investigates the possibility of suppressing the ionization rate in a magnetostatic trap of metastable neon atoms by spin-polarizing the atoms. Suppression of the ionization is critical for the possibility of reaching Bose-Einstein condensation with such atoms. We estimate the relevant long-range interactions for the system, consisting of electric quadrupole-quadrupole and dipole-induced dipole terms, and develop short-range potentials based on the Na_2 singlet and triplet potentials. The auto-ionization widths of the system are also calculated. With these ingredients we calculate the ionization rate for spin-polarized and for spin-isotropic samples, caused by anisotropy of the long-range interactions. We find that spin-polarization may allow for four orders of magnitude suppression of the ionization rate for Ne. The results depend sensitively on a precise knowledge of the interaction potentials, however, pointing out the need for experimental input. The same model gives a suppression ratio close to unity for metastable xenon in accordance with experimental results, due to a much increased anisotropy in this case.Comment: 15 pages including figures, LaTex/RevTex, uses epsfig.st

Addition of local hepatic therapy to sorafenib in patients with advanced hepatocellular carcinoma (stage BCLC C)

BACKGROUND/AIMS For most patients with hepatocellular carcinoma (HCC), diagnosis is invariably done only in the advanced stages of the disease. For advanced, non-metastatic stage, standard therapy is transarterial chemoembolization (TACE). For metastatic disease, the recommended therapy is systemic treatment with sorafenib. In this study, we evaluated the benefit of an additional local hepatic treatment for patients with advanced metastatic disease. METHODS In a retrospective study, we assessed the overall survival (OS), time to progression (TTP), and disease control rate (DCR) in 37 patients with metastasized HCC treated with sorafenib. Sixteen patients received additional local therapy, while 21 patients received only sorafenib. RESULTS Median OS of patients with combined therapy was significantly higher with 25 months (95% CI: 13.7-36.3 months) as compared to 11 months (95% CI: 6.2-15.8 months) in patients treated with sorafenib alone. TTP was 7 months (95% CI: 5.3-8.7 months) compared to 5 months (95% CI: 3-7 months) and DCR was 87 versus 72% after 3 months and 31 versus 22% after 9 months. CONCLUSION These data suggest that control of the liver tumor burden by local therapy in combination with sorafenib might prove beneficial for metastasized HCC. Randomised studies are needed to confirm this exploratory finding

Role of pulmonary intravascular macrophages in endotoxin-induced lung inflammation and mortality in a rat model

<p>Abstract</p> <p>Background</p> <p>Bile-duct ligated (BDL) rats recruit pulmonary intravascular macrophages (PIMs) and are highly susceptible to endotoxin-induced mortality. The mechanisms of this enhanced susceptibility and mortality in BDL rats, which are used as a model of hepato-pulmonary syndrome, remain unknown. We tested a hypothesis that recruited PIMs promote endotoxin-induced mortality in a rat model.</p> <p>Methods</p> <p>Rats were subjected to BDL to induce PIM recruitment followed by treatment with gadolinium chloride (GC) to deplete PIMs. Normal and BDL rats were treated intravenously with <it>E. coli </it>lipopolysaccharide (LPS) with or without GC pre-treatment followed by collection and analyses of lungs for histopathology, electron microscopy and cytokine quantification.</p> <p>Results</p> <p>BDL rats recruited PIMs without any change in the expression of IL-1β, TNF-α and IL-10. GC caused reduction in PIMs at 48 hours post-treatment (P < 0.05). BDL rats treated intravenously with <it>E. coli </it>LPS died within 3 hours of the challenge while the normal LPS-treated rats were euthanized at 6 hours after the LPS treatment. GC treatment of rats 6 hours or 48 hours before LPS challenge resulted in 80% (1/5) and 100% (0/5) survival, respectively, at 6 hours post-LPS treatment. Lungs from BDL+LPS rats showed large areas of perivascular hemorrhages compared to those pre-treated with GC. Concentrations of IL-1β, TNF-α and IL-10 were increased in lungs of BDL+LPS rats compared to BDL rats treated with GC 48 hours but not 6 hours before LPS (P < 0.05).</p> <p>Conclusion</p> <p>We conclude that PIMs increase susceptibility for LPS-induced lung injury and mortality in this model, which is blocked by a reduction in their numbers or their inactivation.</p

Modelling leaf photosynthetic and transpiration temperature-dependent responses in Vitis vinifera cv. Semillon grapevines growing in hot, irrigated vineyard conditions

Grapevines growing in Australia suffer from high temperatures which have major effects on photosynthesis and transpiration. To learn more, gas exchange was measured over several seasons and then modelled across temperatures from 20 to 45°C and validated with independent data

Observation of a J^PC = 1-+ exotic resonance in diffractive dissociation of 190 GeV/c pi- into pi- pi- pi+

The COMPASS experiment at the CERN SPS has studied the diffractive dissociation of negative pions into the pi- pi- pi+ final state using a 190 GeV/c pion beam hitting a lead target. A partial wave analysis has been performed on a sample of 420000 events taken at values of the squared 4-momentum transfer t' between 0.1 and 1 GeV^2/c^2. The well-known resonances a1(1260), a2(1320), and pi2(1670) are clearly observed. In addition, the data show a significant natural parity exchange production of a resonance with spin-exotic quantum numbers J^PC = 1-+ at 1.66 GeV/c^2 decaying to rho pi. The resonant nature of this wave is evident from the mass-dependent phase differences to the J^PC = 2-+ and 1++ waves. From a mass-dependent fit a resonance mass of 1660 +- 10+0-64 MeV/c^2 and a width of 269+-21+42-64 MeV/c^2 is deduced.Comment: 7 page, 3 figures; version 2 gives some more details, data unchanged; version 3 updated authors, text shortened, data unchange

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Author response

Singlet oxygen is a highly toxic and inevitable byproduct of oxygenic photosynthesis. The unicellular green alga Chlamydomonas reinhardtii is capable of acclimating specifically to singlet oxygen stress, but the retrograde signaling pathway from the chloroplast to the nucleus mediating this response is unknown. Here we describe a mutant, singlet oxygen acclimation knocked-out 1 (sak1), that lacks the acclimation response to singlet oxygen. Analysis of genome-wide changes in RNA abundance during acclimation to singlet oxygen revealed that SAK1 is a key regulator of the gene expression response during acclimation. The SAK1 gene encodes an uncharacterized protein with a domain conserved among chlorophytes and present in some bZIP transcription factors. The SAK1 protein is located in the cytosol, and it is induced and phosphorylated upon exposure to singlet oxygen, suggesting that it is a critical intermediate component of the retrograde signal transduction pathway leading to singlet oxygen acclimation. DOI: http://dx.doi.org/10.7554/eLife.02286.00

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

BACKGROUND: For locally advanced squamous cell carcinoma of the head and neck (HNSCC), the recurrence rate after surgery and postoperative radiotherapy is between 20 and 40%, and the 5- year overall survival rate is similar to 50%. Presently, no markers exist to accurately predict treatment outcome. Expression of proteins in the human epidermal growth factor receptor (EGFR) pathway has been reported as a prognostic marker in several types of cancer. METHODS: The aim of this study was to investigate the prognostic value of proteins in the EGFR pathway in HNSCC. For this purpose, we collected surgically resected tissue of 140 locally advanced head and neck cancer patients, all treated with surgery and postoperative radiotherapy. RESULTS: In a multivariate analysis, expression of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was significantly related to worse locoregional control (LRC; HR: 2.2, 95% CI: 1.1-4.6; P = 0.03), independent of lymph node metastases (HR: 5.6, 95% CI: 1.2-27.4; P = 0.03) and extranodal spread (HR: 2.7; 95% CI: 1.2- 6.5; P = 0.02). In vitro clonogenic radiosensitivity assays confirmed that overexpression of PTEN resulted in increased radioresistance. CONCLUSION: Our study is the first report showing that expression of PTEN mediates radiosensitivity in vitro and that increased expression in advanced HNSCC predicts worse LRC. British Journal of Cancer (2010) 102, 1778-1785. doi: 10.1038/sj.bjc.6605707 www.bjcancer.com Published online 25 May 2010 (C) 2010 Cancer Research U