Abiotic formation of O2 and O3 in high-CO2 terrestrial atmospheres

Previous research has indicated that high amounts of ozone (O3) and oxygen (O2) may be produced abiotically in atmospheres with high concentrations of CO2. The abiotic production of these two gases, which are also characteristic of photosynthetic life processes, could pose a potential "false-positive" for remote-sensing detection of life on planets around other stars.We show here that such false positives are unlikely on any planet that possesses abundant liquid water, as rainout of oxidized species onto a reduced planetary surface should ensure that atmospheric H2 concentrations remain relatively high, and that O2 and O3 remain low. Our aim is to determine the amount of O3 and O2 formed in a high CO2 atmosphere for a habitable planet without life. We use a photochemical model that considers hydrogen (H2) escape and a detailed hydrogen balance to calculate the O2 and O3 formed on planets with 0.2 of CO2 around the Sun, and 0.02, 0.2 and 2 bars of CO2 around a young Sun-like star with higher UV radiation. The concentrations obtained by the photochemical model were used as input in a radiative transfer model that calculated the spectra of the modeled planets. The O3 and O2 concentrations in the simulated planets are extremely small, and unlikely to produce a detectable signature in the spectra of those planets. We conclude that with a balanced hydrogen budget, and for planets with an active hydrological cycle, abiotic formation of O2 and O3 is unlikely to create a possible false positive for life detection in either the visible/near-infrared or mid-infrared wavelength regimes.Comment: 27 pages, 15 figures, Astronomy & Astrophysics accepte

Protection and fault detection for Lawrence Berkeley Laboratory neutral beam sources

Testing of TFTR neutral beam (NB) sources has begun at the LBL Neutral Beam System Test Facility (NBSTF). Operation at 120 kV, 65 A, 0.5 sec should be achieved soon. Because NB sources spark down frequently during conditioning, the main accelerating (accel) power supply must be interrupted within a few microseconds to avoid degrading the voltage holding capability, or even the damaging, of the NB source. A variety of improper magnitudes and/or ratios of voltages, currents, and times can occur and must be recognized as fault conditions in order to initiate a prompt interruption of the accel power supply. This paper discusses in detail the key signals which must be monitored and the manner in which they are processed in fault detector circuitry for safe operation of LBL NB sources. The paper also reviews the more standard interlocks and protective features recommended for these sources

Association of warfarin dose with genes involved in its action and metabolism

We report an extensive study of variability in genes encoding proteins that are believed to be involved in the action and biotransformation of warfarin. Warfarin is a commonly prescribed anticoagulant that is difficult to use because of the wide interindividual variation in dose requirements, the narrow therapeutic range and the risk of serious bleeding. We genotyped 201 patients for polymorphisms in 29 genes in the warfarin interactive pathways and tested them for association with dose requirement. In our study, polymorphisms in or flanking the genes VKORC1, CYP2C9, CYP2C18, CYP2C19, PROC, APOE, EPHX1, CALU, GGCX and ORM1-ORM2 and haplotypes of VKORC1, CYP2C9, CYP2C8, CYP2C19, PROC, F7, GGCX, PROZ, F9, NR1I2 and ORM1-ORM2 were associated with dose (P < 0.05). VKORC1, CYP2C9, CYP2C18 and CYP2C19 were significant after experiment-wise correction for multiple testing (P < 0.000175), however, the association of CYP2C18 and CYP2C19 was fully explained by linkage disequilibrium with CYP2C9*2 and/or *3. PROC and APOE were both significantly associated with dose after correction within each gene. A multiple regression model with VKORC1, CYP2C9, PROC and the non-genetic predictors age, bodyweight, drug interactions and indication for treatment jointly accounted for 62% of variance in warfarin dose. Weaker associations observed for other genes could explain up to ∼10% additional dose variance, but require testing and validation in an independent and larger data set. Translation of this knowledge into clinical guidelines for warfarin prescription will be likely to have a major impact on the safety and efficacy of warfarin. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00439-006-0260-8 and is accessible for authorized users

Targeting tissue factor on tumour cells and angiogenic vascular endothelial cells by factor VII-targeted verteporfin photodynamic therapy for breast cancer in vitro and in vivo in mice

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to develop a ligand-targeted photodynamic therapy (tPDT) by conjugating factor VII (fVII) protein with photosensitiser verteporfin in order to overcome the poor selectivity and enhance the effect of non-targeted PDT (ntPDT) for cancer. fVII is a natural ligand for receptor tissue factor (TF) with high affinity and specificity. The reason for targeting receptor TF for the development of tPDT is that TF is a common but specific target on angiogenic tumour vascular endothelial cells (VEC) and many types of tumour cells, including solid tumours and leukaemia.</p> <p>Methods</p> <p>Murine factor VII protein (mfVII) containing a mutation (Lys341Ala) was covalently conjugated via a cross linker EDC with Veterporfin (VP) that was extracted from liposomal Visudyne, and then free VP was separated by Sephadex G50 spin columns. fVII-tPDT using mfVII-VP conjugate, compared to ntPDT, was tested <it>in vitro </it>for the killing of breast cancer cells and VEGF-stimulated VEC and <it>in vivo </it>for inhibiting the tumour growth of breast tumours in a mouse xenograft model.</p> <p>Results</p> <p>We showed that: (i) fVII protein could be conjugated with VP without affecting its binding activity; (ii) fVII-tPDT could selectively kill TF-expressing breast cancer cells and VEGF-stimulated angiogenic HUVECs but had no side effects on non-TF expressing unstimulated HUVEC, CHO-K1 and 293 cells; (iii) fVII targeting enhanced the effect of VP PDT by three to four fold; (iii) fVII-tPDT induced significantly stronger levels of apoptosis and necrosis than ntPDT; and (iv) fVII-tPDT had a significantly stronger effect on inhibiting breast tumour growth in mice than ntPDT.</p> <p>Conclusions</p> <p>We conclude that the fVII-targeted VP PDT that we report here is a novel and effective therapeutic with improved selectivity for the treatment of breast cancer. Since TF is expressed on many types of cancer cells including leukaemic cells and selectively on angiogenic tumour VECs, fVII-tPDT could have broad therapeutic applications for other solid cancers and leukaemia.</p

Comparative study of the extracellular proteome of Sulfolobus species reveals limited secretion

Although a large number of potentially secreted proteins can be predicted on the basis of genomic distribution of signal sequence-bearing proteins, protein secretion in Archaea has barely been studied. A proteomic inventory and comparison of the growth medium proteins in three hyperthermoacidophiles, i.e., Sulfolobus solfataricus, S. acidocaldarius and S. tokodaii, indicates that only few proteins are freely secreted into the growth medium and that the majority originates from cell envelope bound forms. In S. acidocaldarius both cell-associated and secreted α-amylase activities are detected. Inactivation of the amyA gene resulted in a complete loss of activity, suggesting that the same protein is responsible for the a-amylase activity at both locations. It is concluded that protein secretion in Sulfolobus is a limited process, and it is suggested that the S-layer may act as a barrier for the free diffusion of folded proteins into the medium