Loop-Corrected Compactifications of the Heterotic String with Line Bundles

We consider the E8 x E8 heterotic string theory compactified on Calabi-Yau manifolds with bundles containing abelian factors in their structure group. Generic low energy consequences such as the generalised Green-Schwarz mechanism for the multiple anomalous abelian gauge groups are studied. We also compute the holomorphic gauge couplings and induced Fayet-Iliopoulos terms up to one-loop order, where the latter are interpreted as stringy one-loop corrections to the Donaldson-Uhlenbeck-Yau condition. Such models generically have frozen combinations of Kaehler and dilaton moduli. We study concrete bundles with structure group SU(N) x U(1)^M yielding quasi-realistic gauge groups with chiral matter given by certain bundle cohomology classes. We also provide a number of explicit tadpole free examples of bundles defined by exact sequences of sums of line bundles over complete intersection Calabi-Yau spaces. This includes one example with precisely the Standard Model gauge symmetry.Comment: 47 pages, 6 figures, LaTeX, v2: stability discussion in sect. 2.1 slightly extended, refs. added, v3: normalization of Green-Schwarz term correcte

Chiral Supersymmetric Gepner Model Orientifolds

We explicitly construct A-type orientifolds of supersymmetric Gepner models. In order to reduce the tadpole cancellation conditions to a treatable number we explicitly work out the generic form of the one-loop Klein bottle, annulus and Moebius strip amplitudes for simple current extensions of Gepner models. Equipped with these formulas, we discuss two examples in detail to provide evidence that in this setting certain features of the MSSM like unitary gauge groups with large enough rank, chirality and family replication can be achieved.Comment: 37 pages, TeX (harvmac), minor changes, typos corrected, to appear in JHE

Lifting D-Instanton Zero Modes by Recombination and Background Fluxes

We study the conditions under which D-brane instantons in Type II orientifold compactifications generate a non-perturbative superpotential. If the instanton is non-invariant under the orientifold action, it carries four instead of the two Goldstone fermions required for superpotential contributions. Unless these are lifted, the instanton can at best generate higher fermionic F-terms of Beasley-Witten type. We analyse two strategies to lift the additional zero modes. First we discuss the process of instantonic brane recombination in Type IIA orientifolds. We show that in some cases charge invariance of the measure enforces the presence of further zero modes which, unlike the Goldstinos, cannot be absorbed. In other cases, the instanton exhibits reparameterisation zero modes after recombination and a superpotential is generated if these are lifted by suitable closed or open string couplings. In the second part of the paper we address lifting the extra Goldstinos of D3-brane instantons by supersymmetric three-form background fluxes in Type IIB orientifolds. This requires non-trivial gauge flux on the instanton. Only if the part of the fermionic action linear in the gauge flux survives the orientifold projection can the extra Goldstinos be lifted.Comment: 38 pages, 3 figures, 5 tables; v2: Appendix B slightly expanded, minor rewordin

Effects of N-acetyl-cysteine on endothelial function and inflammation in patients with type 2 diabetes mellitus

Endothelial dysfunction has been associated with premature vascular disease. There is increasing data that N-acetyl-cysteine (NAC) may prevent or improve endothelial dysfunction. The aim of this study was to assess the effects of NAC on endothelial function in patients with type 2 diabetes mellitus, a population at high risk for endothelial dysfunction. Twenty-four patients with diabetes mellitus were assigned randomly to initial therapy with either 900 mg NAC or placebo twice daily in a double-blind, cross-over study design. Flowmediated vasodilation (FMD) of the brachial artery was assessed at baseline, after four weeks of therapy, after a four-week wash-out period, and after another four weeks on the opposite treatment. Plasma and red blood cell glutathione levels and high-sensitivity C-reactive protein (CRP) were measured at all four visits. At baseline, FMD was moderately impaired (3.7±2.9%). There was no significant change in FMD after four weeks of NAC therapy as compared to placebo (0.1±3.6% vs. 1.2±4.2%). Similarly, there was no significant change in glutathione levels. However, median CRP decreased from 2.35 to 2.14 mg/L during NAC therapy (p=0.04), while it increased from 2.24 to 2.65 mg/L with placebo. No side effects were noted during the treatment period. In this double-blind, randomized cross-over study, four weeks of oral NAC therapy failed to improve endothelial dysfunction in patients with diabetes mellitus. However, NAC therapy decreased CRP levels, suggesting that this compound may have some efficacy in reducing systemic inflammation

Conservation by trans-border cooperation: population genetic structure and diversity of geoffroy’s bat (Myotis emarginatus) at its north-western european range edge

In the European Union, all bat species are strictly protected and member states must ensure their conservation. However, if populations are genetically structured, conservation units that correspond to whole countries may be too large, putting small populations with specific conservation requirements at risk. Geoffroy’s bat (Myotis emarginatus) has undergone well-documented declines at its north-western European range edge between the 1960 and 1990s and is considered to be negatively affected by habitat fragmentation. Here we analysed the species’ genetic population structure and diversity to identify subpopulations with reduced genetic diversity and to scientifically inform conservation management. We generated 811 microsatellite-based genetic profiles obtained from 42 European nursery colonies and analysed a total of 932 sequences of the hypervariable region II of the mitochondrial control region sampled from across Europe. While two geographically widespread genetic populations were inferred to be present in north-western Europe, both nuclear and mitochondrial genetic diversity were lowest in the areas that had experienced a decline during the last century. A microsatellite-based analysis of demographic history did not permit, however, to unequivocally link that reduced genetic diversity to the population contraction event. Given the large geographic extent of the genetic populations, preserving the connectivity of mating sites requires concerted conservation efforts across multiple political jurisdictions. Genetic monitoring ought to be done on a regular basis to ensure that large-scale connectivity is maintained and further loss of genetic diversity is prevented

Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity.

Adoptive transfer of T cells genetically modified with tumour-specific T-cell receptors (TCR) is a promising novel approach in the treatment of cancer. We have previously isolated an allorestricted MHC class I-restricted TCR with specificity for Formin-like protein 1 (FMNL1) with potent activity against chronic lymphocytic leukaemia cells. CD4(+) T cells have been described to be highly important for tumour elimination although TCR derived from CD4(+) T cells with anti-tumour reactivity have been only rarely described. In this study we aimed to isolate MHC class-II-restricted CD4(+) T cells and TCR with specificity for leukaemia antigens. We used professional antigen-presenting cells pulsed with the leukaemia-associated and tumour-associated antigen FMNL1 for stimulation of autologous T cells in vitro. We isolated two CD4(+) HLA-DR-restricted T-cell clones and T-cell-derived TCR with so far unknown specificity but high reactivity against lymphoma cells and native malignant cells derived from HLA-matched patients with diverse leukaemias. Moreover, characterization of the TCR after TCR gene transfer revealed that specific characteristics of isolated TCR as reactivity in response to Toll-like receptors were transferable on effector cells. Our results have a major impact on the development of novel immunotherapies. They demonstrate that TCR with potent HLA-DR-restricted anti-leukaemic reactivity against so far undefined self-restricted antigens can be isolated from the healthy autorestricted CD4(+) T-cell repertoire and these TCR are highly interesting candidate tools for novel immunotherapies