Statistics in the Landscape of Intersecting Brane Models

An approach towards a statistical survey of four dimensional supersymmetric vacua in the string theory landscape is described and illustrated with three examples of ensembles of intersecting D-brane models. The question whether it is conceivable to make predictions based on statistical distributions is discussed. Especially interesting in this context are possible correlations between low energy observables. As an example we look at correlations between properties of the gauge sector of intersecting D-brane models and Gepner model constructions.Comment: Submitted for the SUSY07 proceedings, 4 pages, 2 figure

Free Fermionic Heterotic Model Building and Root Systems

We consider an alternative derivation of the GSO Projection in the free fermionic construction of the weakly coupled heterotic string in terms of root systems, as well as the interpretation of the GSO Projection in this picture. We then present an algorithm to systematically and efficiently generate input sets (i.e. basis vectors) in order to study Landscape statistics with minimal computational cost. For example, the improvement at order 6 is approximately 10^{-13} over a traditional brute force approach, and improvement increases with order. We then consider an example of statistics on a relatively simple class of models.Comment: Standard Latex, 12 page

Development and operalisation of a support programme for nursing service managers: Part 2

This paper describes research conducted to develop and implement a support programme for nursing service managers suffering from fatigue. The support programme was developed on the basis of results obtained from a survey that ascertained nursing service managers' views about the problems they were experiencing in their everyday lives. A multiple case-study design was utilised to describe the operationalisation of the support programme. The sample consisted of forty-eight English speaking and fifty-two Afrikaans speaking nursing service managers from the old Transvaal region (Gauteng, North West and Eastern Transvaal The support programme was implemented during two one-day workshops, one with the Afrikaans speaking group and one with the English speaking group of nursing service managers. Data were gathered about operationalisation of the support programme through multiple methods: observation, audiotape recordings, written documents and field notes. The data were analysed by utilising the methods of descriptive analysis

The Stability of a Model Substrate for Topoisomerase 1-Mediated DNA Religation Depends on the Presence of Mismatched Base Pairs

Topoisomerase 1 (Top1) enzymes regulate DNA superhelicity by forming covalent cleavage complexes that undergo controlled rotation. Substitution of nucleoside analogs at the +1 position of the DNA duplex relative to the Top1 cleavage site inhibits DNA religation. The reduced efficiency for Top1-mediated religation contributes to the anticancer activity of widely used anticancer drugs including fluoropyrimidines and gemcitabine. In the present study, we report that mismatched base pairs at the +1 position destabilize the duplex DNA components for a model Top1 cleavage complex formation even though one duplex component does not directly include a mismatched base pair. Molecular dynamics simulations reveal G-dU and G-FdU mismatched base pairs, but not a G-T mismatched base pair, increase flexibility at the Top1 cleavage site, and affect coupling between the regions required for the religation reaction to occur. These results demonstrate that substitution of dT analogs into the +1 position of the non-scissile strand alters the stability and flexibility of DNA contributing to the reduced efficiency for Top1-mediated DNA religation. These effects are inherent in the DNA duplex and do not require formation of the Top1:DNA complex. These results provide a biophysical rationale for the inhibition of Top1-mediated DNA religation by nucleotide analog substitution

Selection Of A Novel Aptamer Against Vitronectin Using Capillary Electrophoresis And Next Generation Sequencing

Breast cancer (BC) results in ≃40,000 deaths each year in the United States and even among survivors treatment of the disease may have devastating consequences, including increased risk for heart disease and cognitive impairment resulting from the toxic effects of chemotherapy. Aptamer-mediated drug delivery can contribute to improved treatment outcomes through the selective delivery of chemotherapy to BC cells, provided suitable cancer-specific antigens can be identified. We report here the use of capillary electrophoresis in conjunction with next generation sequencing to develop the first vitronectin (VN) binding aptamer (VBA-01; Kd 405 nmol/l, the first aptamer to vitronectin (VN; Kd = 405 nmol/l), a protein that plays an important role in wound healing and that is present at elevated levels in BC tissue and in the blood of BC patients relative to the corresponding nonmalignant tissues. We used VBA-01 to develop DVBA-01, a dimeric aptamer complex, and conjugated doxorubicin (Dox) to DVBA-01 (7:1 ratio) using pH-sensitive, covalent linkages. Dox conjugation enhanced the thermal stability of the complex (60.2 versus 46.5°C) and did not decrease affinity for the VN target. The resulting DVBA-01-Dox complex displayed increased cytotoxicity to MDA-MB-231 BC cells that were cultured on plasticware coated with VN (1.8 × 10⁻⁶mol/l) relative to uncoated plates (2.4 × 10⁻⁶ mol/l), or plates coated with the related protein fibronectin (2.1 × 10⁻⁶ mol/l). The VBA-01 aptamer was evaluated for binding to human BC tissue using immunohistochemistry and displayed tissue specific binding and apparent association with BC cells. In contrast, a monoclonal antibody that preferentially binds to multimeric VN primarily stained extracellular matrix and vessel walls of BC tissue. Our results indicate a strong potential for using VN-targeting aptamers to improve drug delivery to treat BC

Optimizing the Expression of Human Dopamine Receptors in Escherichia coli

The human dopamine receptors D2S and D3 belong to the group of G protein-coupled receptors (GPCRs) and are important drug targets. Structural analyses and development of new receptor subtype specific drugs have been impeded by low expression yields or receptor instability. Fusing the T4 lysozyme into the intracellular loop 3 improves crystallization but complicates conformational studies. To circumvent these problems, we expressed the human D2S and D3 receptors in Escherichia coli using different N- and C-terminal fusion proteins and thermostabilizing mutations. We optimized expression times and used radioligand binding assays with whole cells and membrane homogenates to evaluate KD-values and the number of receptors in the cell membrane. We show that the presence but not the type of a C-terminal fusion protein is important. Bacteria expressing receptors capable of ligand binding can be selected using FACS analysis and a fluorescently labeled ligand. Improved receptor variants can thus be generated using error-prone PCR. Subsequent analysis of clones showed the distribution of mutations over the whole gene. Repeated cycles of PCR and FACS can be applied for selecting highly expressing receptor variants with high affinity ligand binding, which in the future can be used for analytical studies

The UEFA EURO 2012 anti-doping programme - scientific review

The final tournament of the UEFA European Football Championship is one of the top sporting events in the world, and a high-profile event of this kind requires a well-planned and well-executed anti-doping programme to ensure the integrity of results in the competition. UEFA EURO 2012 presented a unique logistical challenge, with the tournament spread across two countries, both covering a large geographical area. This paper discusses the planning and delivery of both the pre tournament out-of-competition (OOC) testing programme and the in-competition (IC) programme, as well as reviewing the activities of doping control officers (DCOs), the whereabouts programme and assessing the sample collection and transport process. The analytical approach applied is also discussed, along with an overview of the distribution of T/E ratios and blood parameters

Yukawa couplings and masses of non-chiral states for the Standard Model on D6-branes on T6/Z6'

The perturbative leading order open string three-point couplings for the Standard Model with hidden USp(6) on fractional D6-branes on T6/Z6' from arXiv:0806.3039 [hep-th], arXiv:0910.0843 [hep-th] are computed. Physical Yukawa couplings consisting of holomorphic Wilsonian superpotential terms times a non-holomorphic prefactor involving the corresponding classical open string Kaehler metrics are given, and mass terms for all non-chiral matter states are derived. The lepton Yukawa interactions are at leading order flavour diagonal, while the quark sector displays a more intricate pattern of mixings. While N=2 supersymmetric sectors acquire masses via only two D6-brane displacements - which also provide the hierarchies between up- and down-type Yukawas within one quark or lepton generation -, the remaining vector-like states receive masses via perturbative three-point couplings to some Standard Model singlet fields with vevs along flat directions. Couplings to the hidden sector and messengers for supersymmetry breaking are briefly discussed.Comment: 52 pages (including 8p. appendix); 5 figures; 14 tables; v2: discussion in section 4.1.3 extended, footnote 5 added, typos corrected, accepted by JHE

Localized tadpoles of anomalous heterotic U(1)'s

We investigate the properties of localized anomalous U(1)'s in heterotic string theory on the orbifold T^6/Z_3. We argue that the local four dimensional and original ten dimensional Green-Schwarz mechanisms can be implemented simultaneously, making the theory manifestly gauge invariant everywhere, in the bulk and at the fixed points. We compute the shape of the Fayet-Iliopoulos tadpoles, and cross check this derivation for the four dimensional auxiliary fields by a direct calculation of the tadpoles of the internal gauge fields. Finally we study some resulting consequences for spontaneous symmetry breaking, and derive the profile of the internal gauge field background over the orbifold.Comment: 35 pages, LaTeX, with figure