G-structures and Domain Walls in Heterotic Theories

We consider heterotic string solutions based on a warped product of a four-dimensional domain wall and a six-dimensional internal manifold, preserving two supercharges. The constraints on the internal manifolds with SU(3) structure are derived. They are found to be generalized half-flat manifolds with a particular pattern of torsion classes and they include half-flat manifolds and Strominger's complex non-Kahler manifolds as special cases. We also verify that previous heterotic compactifications on half-flat mirror manifolds are based on this class of solutions.Comment: 29 pages, reference added, typos correcte

Stabilizing the Complex Structure in Heterotic Calabi-Yau Vacua

In this paper, we show that the presence of gauge fields in heterotic Calabi-Yau compacitifications causes the stabilisation of some, or all, of the complex structure moduli of the Calabi-Yau manifold while maintaining a Minkowski vacuum. Certain deformations of the Calabi-Yau complex structure, with all other moduli held fixed, can lead to the gauge bundle becoming non-holomorphic and, hence, non-supersymmetric. This leads to an F-term potential which stabilizes the corresponding complex structure moduli. We use 10- and 4-dimensional field theory arguments as well as a derivation based purely on algebraic geometry to show that this picture is indeed correct. An explicit example is presented in which a large subset of complex structure moduli is fixed. We demonstrate that this type of theory can serve as the hidden sector in heterotic vacua and can co-exist with realistic particle physics.Comment: 17 pages, Late

Interplay between pleiotropy and secondary selection determines rise and fall of mutators in stress response

Dramatic rise of mutators has been found to accompany adaptation of bacteria in response to many kinds of stress. Two views on the evolutionary origin of this phenomenon emerged: the pleiotropic hypothesis positing that it is a byproduct of environmental stress or other specific stress response mechanisms and the second order selection which states that mutators hitchhike to fixation with unrelated beneficial alleles. Conventional population genetics models could not fully resolve this controversy because they are based on certain assumptions about fitness landscape. Here we address this problem using a microscopic multiscale model, which couples physically realistic molecular descriptions of proteins and their interactions with population genetics of carrier organisms without assuming any a priori fitness landscape. We found that both pleiotropy and second order selection play a crucial role at different stages of adaptation: the supply of mutators is provided through destabilization of error correction complexes or fluctuations of production levels of prototypic mismatch repair proteins (pleiotropic effects), while rise and fixation of mutators occur when there is a sufficient supply of beneficial mutations in replication-controlling genes. This general mechanism assures a robust and reliable adaptation of organisms to unforeseen challenges. This study highlights physical principles underlying physical biological mechanisms of stress response and adaptation

Out-of-hours primary care. Implications of organisation on costs

BACKGROUND: To perform out-of-hours primary care, Dutch general practitioners (GPs) have organised themselves in large-scale GP cooperatives. Roughly, two models of out-of-hours care can be distinguished; GP cooperatives working separate from the hospital emergency department (ED) and GP cooperatives integrated with the hospital ED. Research has shown differences in care utilisation between these two models; a significant shift in the integrated model from utilisation of ED care to primary care. These differences may have implications on costs, however, until now this has not been investigated. This study was performed to provide insight in costs of these two different models of out-of-hours care. METHODS: Annual reports of two GP cooperatives (one separate from and one integrated with a hospital emergency department) in 2003 were analysed on costs and use of out-of-hours care. Costs were calculated per capita. Comparisons were made between the two cooperatives. In addition, a comparison was made between the costs of the hospital ED of the integrated model before and after the set up of the GP cooperative were analysed. RESULTS: Costs per capita of the GP cooperative in the integrated model were slightly higher than in the separate model (ε 11.47 and ε 10.54 respectively). Differences were mainly caused by personnel and other costs, including transportation, interest, cleaning, computers and overhead. Despite a significant reduction in patients utilising ED care as a result of the introduction of the GP cooperative integrated within the ED, the costs of the ED remained the same. CONCLUSION: The study results show that the costs of primary care appear to be more dependent on the size of the population the cooperative covers than on the way the GP cooperative is organised, i.e. separated versus integrated. In addition, despite the substantial reduction of patients, locating the GP cooperative at the same site as the ED was found to have little effect on costs of the ED. Sharing more facilities and personnel between the ED and the GP cooperative may improve cost-efficiency

Entanglement of Imaging and Imagining of Nanotechnology

Images, ranging from visualizations of the nanoscale to future visions, abound within and beyond the world of nanotechnology. Rather than the contrast between imaging, i.e. creating images that are understood as offering a view on what is out there, and imagining, i.e. creating images offering impressions of how the nanoscale could look like and images presenting visions of worlds that might be realized, it is the entanglement between imaging and imagining which is the key to understanding what images do. Three main arenas of entanglement of imag(in)ing and the tensions involved are discussed: production practices and use of visualizations of the nanoscale; imag(in)ing the future and the present; and entanglements of nanoscience and art. In these three arenas one sees struggles about which images might stand for nanotechnology, but also some stabilization of the entanglement of imag(in)ing, for example in established rules in the practices of visualizing the nanoscale. Three images have become iconic, through the combination of their wide reception and further circulation. All three, the IBM logo, the Foresight Institute’s Nanogear image, and the so-called Nanolouse, depict actual or imagined technoscientific objects and are thus seen as representing technoscientific achievements – while marking out territory

Heterotic Line Bundle Standard Models

In a previous publication, arXiv:1106.4804, we have found 200 models from heterotic Calabi-Yau compactifications with line bundles, which lead to standard models after taking appropriate quotients by a discrete symmetry and introducing Wilson lines. In this paper, we construct the resulting standard models explicitly, compute their spectrum including Higgs multiplets, and analyze some of their basic properties. After removing redundancies we find about 400 downstairs models, each with the precise matter spectrum of the supersymmetric standard model, with one, two or three pairs of Higgs doublets and no exotics of any kind. In addition to the standard model gauge group, up to four Green-Schwarz anomalous U(1) symmetries are present in these models, which constrain the allowed operators in the four-dimensional effective supergravity. The vector bosons associated to these anomalous U(1) symmetries are massive. We explicitly compute the spectrum of allowed operators for each model and present the results, together with the defining data of the models, in a database of standard models accessible at http://www-thphys.physics.ox.ac.uk/projects/CalabiYau/linebundlemodels/index.html. Based on these results we analyze elementary phenomenological properties. For example, for about 200 models all dimension four and five proton decay violating operators are forbidden by the additional U(1) symmetries.Comment: 55 pages, Latex, 3 pdf figure

Dissecting complex transcriptional responses using pathway-level scores based on prior information

<p>Abstract</p> <p>Background</p> <p>The genomewide pattern of changes in mRNA expression measured using DNA microarrays is typically a complex superposition of the response of multiple regulatory pathways to changes in the environment of the cells. The use of prior information, either about the function of the protein encoded by each gene, or about the physical interactions between regulatory factors and the sequences controlling its expression, has emerged as a powerful approach for dissecting complex transcriptional responses.</p> <p>Results</p> <p>We review two different approaches for combining the noisy expression levels of multiple individual genes into robust pathway-level differential expression scores. The first is based on a comparison between the distribution of expression levels of genes within a predefined gene set and those of all other genes in the genome. The second starts from an estimate of the strength of genomewide regulatory network connectivities based on sequence information or direct measurements of protein-DNA interactions, and uses regression analysis to estimate the activity of gene regulatory pathways. The statistical methods used are explained in detail.</p> <p>Conclusion</p> <p>By avoiding the thresholding of individual genes, pathway-level analysis of differential expression based on prior information can be considerably more sensitive to subtle changes in gene expression than gene-level analysis. The methods are technically straightforward and yield results that are easily interpretable, both biologically and statistically.</p

Longevity and Composition of Cellular Immune Responses Following Experimental Plasmodium falciparum Malaria Infection in Humans

Cellular responses to Plasmodium falciparum parasites, in particular interferon-gamma (IFNγ) production, play an important role in anti-malarial immunity. However, clinical immunity to malaria develops slowly amongst naturally exposed populations, the dynamics of cellular responses in relation to exposure are difficult to study and data about the persistence of such responses are controversial. Here we assess the longevity and composition of cellular immune responses following experimental malaria infection in human volunteers. We conducted a longitudinal study of cellular immunological responses to sporozoites (PfSpz) and asexual blood-stage (PfRBC) malaria parasites in naïve human volunteers undergoing single (n = 5) or multiple (n = 10) experimental P. falciparum infections under highly controlled conditions. IFNγ and interleukin-2 (IL-2) responses following in vitro re-stimulation were measured by flow-cytometry prior to, during and more than one year post infection. We show that cellular responses to both PfSpz and PfRBC are induced and remain almost undiminished up to 14 months after even a single malaria episode. Remarkably, not only ‘adaptive’ but also ‘innate’ lymphocyte subsets contribute to the increased IFNγ response, including αβT cells, γδT cells and NK cells. Furthermore, results from depletion and autologous recombination experiments of lymphocyte subsets suggest that immunological memory for PfRBC is carried within both the αβT cells and γδT compartments. Indeed, the majority of cytokine producing T lymphocytes express an CD45RO+ CD62L- effector memory (EM) phenotype both early and late post infection. Finally, we demonstrate that malaria infection induces and maintains polyfunctional (IFNγ+IL-2+) EM responses against both PfRBC and PfSpz, previously found to be associated with protection. These data demonstrate that cellular responses can be readily induced and are long-lived following infection with P. falciparum, with a persisting contribution by not only adaptive but also (semi-)innate lymphocyte subsets. The implications hereof are positive for malaria vaccine development, but focus attention on those factors potentially inhibiting such responses in the field

Effects of Transcriptional Pausing on Gene Expression Dynamics

Stochasticity in gene expression affects many cellular processes and is a source of phenotypic diversity between genetically identical individuals. Events in elongation, particularly RNA polymerase pausing, are a source of this noise. Since the rate and duration of pausing are sequence-dependent, this regulatory mechanism of transcriptional dynamics is evolvable. The dependency of pause propensity on regulatory molecules makes pausing a response mechanism to external stress. Using a delayed stochastic model of bacterial transcription at the single nucleotide level that includes the promoter open complex formation, pausing, arrest, misincorporation and editing, pyrophosphorolysis, and premature termination, we investigate how RNA polymerase pausing affects a gene's transcriptional dynamics and gene networks. We show that pauses' duration and rate of occurrence affect the bursting in RNA production, transcriptional and translational noise, and the transient to reach mean RNA and protein levels. In a genetic repressilator, increasing the pausing rate and the duration of pausing events increases the period length but does not affect the robustness of the periodicity. We conclude that RNA polymerase pausing might be an important evolvable feature of genetic networks