Diversity in the Tail of the Intersecting Brane Landscape

Techniques are developed for exploring the complete space of intersecting brane models on an orientifold. The classification of all solutions for the widely-studied T^6/Z_2 x Z_2 orientifold is made possible by computing all combinations of branes with negative tadpole contributions. This provides the necessary information to systematically and efficiently identify all models in this class with specific characteristics. In particular, all ways in which a desired group G can be realized by a system of intersecting branes can be enumerated in polynomial time. We identify all distinct brane realizations of the gauge groups SU(3) x SU(2) and SU(3) x SU(2) x U(1) which can be embedded in any model which is compatible with the tadpole and SUSY constraints. We compute the distribution of the number of generations of "quarks" and find that 3 is neither suppressed nor particularly enhanced compared to other odd generation numbers. The overall distribution of models is found to have a long tail. Despite disproportionate suppression of models in the tail by K-theory constraints, the tail in the distribution contains much of the diversity of low-energy physics structure.Comment: 48 pages, 8 figure

Power of Black Hole Physics: Seeing through the Vacuum Landscape

In this paper we generalize the black hole bound of arXiv:0706.2050 to de Sitter spaces, and apply it to various vacua in the landscape, with a special emphasis on slow-roll inflationary vacua. Non-trivial constraints on the lifetime and the Hubble expansion rate emerge. For example, the general tendency is, that for the fixed number and the increasing mass of the species, vacua must become more curved and more unstable, either classically or quantum mechanically. We also discuss the constraints on the lifetime of vacua in the landscape, due to decay into the neighboring states.Comment: 33 page

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

Model building with intersecting D6-branes on smooth Calabi-Yau manifolds

We study intersecting D6-branes in Calabi-Yau manifolds that are smooth hypersurfaces in weighted projective spaces. We develop the techniques for calculating intersection numbers between special Lagrangian sub-manifolds defined as fixed loci of anti-holomorphic involutions. We present global Pati-Salam and MSSM-like models that are supersymmetric up to a decoupled hidden sector.Comment: 29p

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

Guardians and research staff experiences and views about the consent process in hospital-based paediatric research studies in urban Malawi: A qualitative study

Background: Obtaining consent has become a standard way of respecting the patient’s rights and autonomy in clinical research. Ethical guidelines recommend that the child’s parent/s or authorised legal guardian provides informed consent for their child’s participation. However, obtaining informed consent in paediatric research is challenging. Parents become vulnerable because of stress related to their child’s illness. Understanding the views held by guardians and researchers about the consent process in Malawi, where there are limitations in health care access and research literacy will assist in developing appropriate consent guidelines. Methods: We conducted 20 in-depth interviews with guardians of children and research staff who had participated in paediatric clinical trial and observational studies in acute and non-acute settings in the Southern Region of Malawi. Interviews were audio-recorded, transcribed verbatim, and thematically analysed. Interviews were compared across studies and settings to identify differences and similarities in participants’ views about informed consent processes. Data analysis was facilitated by NVIVO 11 software. Results: All participants across study types and settings reported that they associated participating in research with therapeutic benefits. Substantial differences were noted in the decision-making process across study settings. Guardians from acute studies felt that the role of their spouses was neglected during consenting, while staff reported that they had problems obtaining consent from guardians when their partners were not present. Across all study types and settings, research staff reported that they emphasised the benefits more than the risks of the study to participants, due to pressure to recruit. Participants from non-acute settings were more likely to recall information shared during the consent process than participants in the acute setting. Conclusion: The health care context, culture and research process influenced participants’ understanding of study information across study types and settings. We advise research managers or principal investigators to define minimum requirements that would not compromise the consent process and conduct study specific training for staff. The use of one size fits all consent process may not be ideal. More guidance is needed on how these differences can be incorporated during the consent process to improve understanding and delivery of consent

Intersecting D-Branes on Shift Z2 x Z2 Orientifolds

We investigate Z2 x Z2 orientifolds with group actions involving shifts. A complete classification of possible geometries is presented where also previous work by other authors is included in a unified framework from an intersecting D-brane perspective. In particular, we show that the additional shifts not only determine the topology of the orbifold but also independently the presence of orientifold planes. In the second part, we work out in detail a basis of homological three cycles on shift Z2 x Z2 orientifolds and construct all possible fractional D-branes including rigid ones. A Pati-Salam type model with no open-string moduli in the visible sector is presented.Comment: 36 pages, 4 figures, refs. adde

Rapidly-Varying Speed of Sound, Scale Invariance and Non-Gaussian Signatures

We show that curvature perturbations acquire a scale invariant spectrum for any constant equation of state, provided the fluid has a suitably time-dependent sound speed. In order for modes to exit the physical horizon, and in order to solve the usual problems of standard big bang cosmology, we argue that the only allowed possibilities are inflationary (albeit not necessarily slow-roll) expansion or ekpyrotic contraction. Non-Gaussianities offer many distinguish features. As usual with a small sound speed, non-Gaussianity can be relatively large, around current sensitivity levels. For DBI-like lagrangians, the amplitude is negative in the inflationary branch, and can be either negative or positive in the ekpyrotic branch. Unlike the power spectrum, the three-point amplitude displays a large tilt that, in the expanding case, peaks on smallest scales. While the shape is predominantly of the equilateral type in the inflationary branch, as in DBI inflation, it is of the local form in the ekpyrotic branch. The tensor spectrum is also generically far from scale invariant. In the contracting case, for instance, tensors are strongly blue tilted, resulting in an unmeasurably small gravity wave amplitude on cosmic microwave background scales.Comment: 41 pages, 12 figures. v4: Few typos in equations (7.39) correcte

On Susy Standard-like models from orbifolds of D=6 Gepner orientifolds

As a further elaboration of the proposal of Ref. [1] we address the construction of Standard-like models from configurations of stacks of orientifold planes and D-branes on an internal space with the structure ${(Gepner model)^{c=6} \times T^2}/Z_N$. As a first step, the construction of D=6 Type II B orientifolds on Gepner points, in the diagonal invariant case and for both, odd and even, affine levels is discussed. We build up the explicit expressions for B-type boundary states and crosscaps and obtain the amplitudes among them. From such amplitudes we read the corresponding spectra and the tadpole cancellation equations. Further compactification on a T^2 torus, by simultaneously orbifolding the Gepner and the torus internal sectors, is performed. The embedding of the orbifold action in the brane sector breaks the original gauge groups and leads to N=1 supersymmetric chiral spectra. Whenever even orbifold action on the torus is considered, new branes, with worldvolume transverse to torus coordinates, must be included. The detailed rules for obtaining the D=4 model spectra and tadpole equations are shown. As an illustration we present a 3 generations Left-Right symmetric model that can be further broken to a MSSM model.Comment: 40 pages, 2 figures, added references, table 3 correcte