Irradiation-driven mass transfer cycles in compact binaries

We elaborate on the analytical model of Ritter, Zhang, and Kolb (2000, A&A 360, 959) which describes the basic physics of irradiation-driven mass transfer cycles in semi-detached compact binary systems. In particular, we take into account a contribution to the thermal relaxation of the donor star which is unrelated to irradiation and which was neglected in previous studies. We present results of simulations of the evolution of compact binaries undergoing mass transfer cycles, in particular also of systems with a nuclear evolved donor star. These computations have been carried out with a stellar evolution code which computes mass transfer implicitly and models irradiation of the donor star in a point source approximation, thereby allowing for more realistic simulations than were hitherto possible. We find that low-mass X-ray binaries and cataclysmic variables with orbital periods less than about 6 hours can undergo mass transfer cycles only for low angular momentum loss rates. CVs containing a giant donor or one near the terminal age main sequence are more stable than previously thought, but can possibly also undergo mass transfer cycles.Comment: 6 pages, LaTeX, one eps figure, requires asp2004.sty, to appear in: The Astrophysics of Cataclysmic Variables and Related Objects, ASP Conf. Ser., Vol. ?, 2005, J.M. Hameury and J.P. Lasota (eds.

The chemically zoned 1949 eruption on La Palma (Canary Islands): Petrologic evolution and magma supply dynamics of a rift zone eruption

The 1949 rift zone eruption along the Cumbre Vieja ridge on La Palma involved three eruptive centers, 3 km spaced apart, and was chemically and mineralogically zoned. Duraznero crater erupted tephrite for 14 days and shut down upon the opening of Llano del Banco, a fissure that issued first tephrite and, after 3 days, basanite. Hoyo Negro crater opened 4 days later and erupted basanite, tephrite, and phonotephrite, while Llano del Banco continued to issue basanite. The eruption ended with Duraznero erupting basanite with abundant crustal and mantle xenoliths. The tephrites and basanites from Duraznero and Llano del Banco show narrow compositional ranges and define a bimodal suite. Each batch ascended and evolved separately without significant intermixing, as did the Hoyo Negro basanite, which formed at lower degrees of melting. The magmas fractionated clinopyroxene +olivine±kaersutite±Ti-magnetite at 600–800 MPa and possibly 800–1100 MPa. Abundant reversely zoned phenocrysts reflect mixing with evolved melts at mantle depths. Probably as early as 1936, Hoyo Negro basanite entered the deep rift system at 200–350 MPa. Some shallower pockets of this basanite evolved to phonotephrite through differentiation and assimilation of wall rock. A few months prior to eruption, a mixing event in the mantle may have triggered the final ascent of the magmas. Most of the erupted tephrite and basanite ascended from mantle depths within hours to days without prolonged storage in crustal reservoirs. The Cumbre Vieja rift zone differs from the rift zones of Kilauea volcano (Hawaii) in lacking a summit caldera or a summit reservoir feeding the rift system and in being smaller and less active with most of the rift magma solidifying between eruptions

The N-Terminal Domain of NLRC5 Confers Transcriptional Activity for MHC Class I and II Gene Expression

Ag presentation to CD4(+) and CD8(+) T cells depends on MHC class II and MHC class I molecules, respectively. One important regulatory factor of this process is the transcriptional regulation of MHC gene expression. It is well established that MHC class II transcription relies on the NLR protein CIITA. Recently, another NLR protein, NLRC5, was shown to drive MHC class I expression. The molecular mechanisms of the function of NLRC5 however remain largely elusive. In this study, we present a detailed functional study of the domains of NLRC5 revealing that the N-terminal domain of human NLRC5 has intrinsic transcriptional activity. Domain swapping experiments between NLRC5 and CIITA showed that this domain contributes to MHC class I and MHC class II gene expression with a bias for activation of MHC class I promoters. Delivery of this construct by adeno-associated viral vectors upregulated MHC class I and MHC class II expression in human cells and enhanced lysis of melanoma cells by CD8(+) cytotoxic T cells in vitro. Taken together, this work provides novel insight into the function of NLRC5 and CIITA in MHC gene regulation

Off-target-free gene delivery by affinity-purified receptor-targeted viral vectors

We describe receptor-targeted adeno-associated viral (AAV) vectors that allow genetic modification of rare cell types ex vivo and in vivo while showing no detectable off-targeting. Displaying designed ankyrin repeat proteins (DARPins) on the viral capsid and carefully depleting DARPin-deficient particles, AAV vectors were made specific for Her2/neu, EpCAM or CD4. A single intravenous administration of vector targeted to the tumour antigen Her2/neu was sufficient to track 75% of all tumour sites and to extend survival longer than the cytostatic antibody Herceptin. CD4-targeted AAVs hit human CD4-positive cells present in spleen of a humanized mouse model, while CD8-positive cells as well as liver or other off-target organs remained unmodified. Mimicking conditions of circulating tumour cells, EpCAM-AAV detected single tumour cells in human blood opening the avenue for tumour stem cell tracking. Thus, the approach developed here delivers genes to target cell types of choice with antibody-like specificity

Association Between Variants of PRDM1 and NDP52 and Crohn's Disease, Based on Exome Sequencing and Functional Studies

<p>BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified 140 Crohn's disease (CD) susceptibility loci. For most loci, the variants that cause disease are not known and the genes affected by these variants have not been identified. We aimed to identify variants that cause CD through detailed sequencing, genetic association, expression, and functional studies. METHODS: We sequenced whole exomes of 42 unrelated subjects with CD and 5 healthy subjects (controls) and then filtered single nucleotide variants by incorporating association results from meta-analyses of CD GWAS and in silico mutation effect prediction algorithms. We then genotyped 9348 subjects with CD, 2868 subjects with ulcerative colitis, and 14,567 control subjects and associated variants analyzed in functional studies using materials from subjects and controls and in vitro model systems. RESULTS: We identified rare missense mutations in PR domain-containing 1 (PRDM1) and associated these with CD. These mutations increased proliferation of T cells and secretion of cytokines on activation and increased expression of the adhesion molecule L-selectin. A common CD risk allele, identified in GWAS, correlated with reduced expression of PRDM1 in ileal biopsy specimens and peripheral blood mononuclear cells (combined P = 1.6 x 10(-8)). We identified an association between CD and a common missense variant, Val248Ala, in nuclear domain 10 protein 52 (NDP52) (P = 4.83 x 10(-9)). We found that this variant impairs the regulatory functions of NDP52 to inhibit nuclear factor kappa B activation of genes that regulate inflammation and affect the stability of proteins in Toll-like receptor pathways. CONCLUSIONS: We have extended the results of GWAS and provide evidence that variants in PRDM1 and NDP52 determine susceptibility to CD. PRDM1 maps adjacent to a CD interval identified in GWAS and encodes a transcription factor expressed by T and B cells. NDP52 is an adaptor protein that functions in selective autophagy of intracellular bacteria and signaling molecules, supporting the role of autophagy in the pathogenesis of CD.</p>