98 research outputs found
Six-dimensional (1,0) effective action of F-theory via M-theory on Calabi-Yau threefolds
The six-dimensional effective action of F-theory compactified on a singular
elliptically fibred Calabi-Yau threefold is determined by using an M-theory
lift. The low-energy data are derived by comparing a circle reduction of a
general six-dimensional (1,0) gauged supergravity theory with the effective
action of M-theory on the resolved Calabi-Yau threefold. The derivation
includes six-dimensional tensor multiplets for which the (anti-) self-duality
constraints are imposed on the level of the five-dimensional action. The vector
sector of the reduced theory is encoded by a non-standard potential due to the
Green-Schwarz term in six dimensions. This Green-Schwarz term also contains
higher curvature couplings which are considered to establish the full map
between anomaly coefficients and geometry. F-/M-theory duality is exploited by
moving to the five-dimensional Coulomb branch after circle reduction and
integrating out massive vector multiplets and matter hypermultiplets. The
associated fermions then generate additional Chern-Simons couplings at
one-loop. Further couplings involving the graviphoton are induced by quantum
corrections due to excited Kaluza-Klein modes. On the M-theory side integrating
out massive fields corresponds to resolving the singularities of the Calabi-Yau
threefold, and yields intriguing relations between six-dimensional anomalies
and classical topology.Comment: 55 pages, v2: typos corrected, discussion of loop corrections
improve
Anomaly Cancelation in Field Theory and F-theory on a Circle
We study the manifestation of local gauge anomalies of four- and
six-dimensional field theories in the lower-dimensional Kaluza-Klein theory
obtained after circle compactification. We identify a convenient set of
transformations acting on the whole tower of massless and massive states and
investigate their action on the low-energy effective theories in the Coulomb
branch. The maps employ higher-dimensional large gauge transformations and
precisely yield the anomaly cancelation conditions when acting on the one-loop
induced Chern-Simons terms in the three- and five-dimensional effective theory.
The arising symmetries are argued to play a key role in the study of the
M-theory to F-theory limit on Calabi-Yau manifolds. For example, using the fact
that all fully resolved F-theory geometries inducing multiple Abelian gauge
groups or non-Abelian groups admit a certain set of symmetries, we are able to
generally show the cancelation of pure Abelian or pure non-Abelian anomalies in
these models.Comment: 48 pages, 2 figures; v2: typos corrected, comments on circle fluxes
adde
D3-brane Potentials from Fluxes in AdS/CFT
We give a comprehensive treatment of the scalar potential for a D3-brane in a
warped conifold region of a compactification with stabilized moduli. By
studying general ultraviolet perturbations in supergravity, we systematically
incorporate `compactification effects' sourced by supersymmetry breaking in the
compact space. Significant contributions to the D3-brane potential, including
the leading term in the infrared, arise from imaginary anti-self-dual (IASD)
fluxes. For an arbitrary Calabi-Yau cone, we determine the most general IASD
fluxes in terms of scalar harmonics, then compute the resulting D3-brane
potential. Specializing to the conifold, we identify the operator dual to each
mode of flux, and for chiral operators we confirm that the potential computed
in the gauge theory matches the gravity result. The effects of four-dimensional
curvature, including the leading D3-brane mass term, arise directly from the
ten-dimensional equations of motion. Furthermore, we show that gaugino
condensation on D7-branes provides a local source for IASD flux. This flux
precisely encodes the nonperturbative contributions to the D3-brane potential,
yielding a promising ten-dimensional representation of four-dimensional
nonperturbative effects. Our result encompasses all significant contributions
to the D3-brane potential discussed in the literature, and does so in the
single coherent framework of ten-dimensional supergravity. Moreover, we
identify new terms with irrational scaling dimensions that were inaccessible in
prior works. By decoupling gravity in a noncompact configuration, then
systematically reincorporating compactification effects as ultraviolet
perturbations, we have provided an approach in which Planck-suppressed
contributions to the D3-brane effective action can be computed.Comment: 70 page
Massive Abelian Gauge Symmetries and Fluxes in F-theory
F-theory compactified on a Calabi-Yau fourfold naturally describes
non-Abelian gauge symmetries through the singularity structure of the elliptic
fibration. In contrast Abelian symmetries are more difficult to study because
of their inherently global nature. We argue that in general F-theory
compactifications there are massive Abelian symmetries, such as the uplift of
the Abelian part of the U(N) gauge group on D7-branes, that arise from
non-Kahler resolutions of the dual M-theory setup. The four-dimensional
F-theory vacuum with vanishing expectation values for the gauge fields
corresponds to the Calabi-Yau limit. We propose that fluxes that are turned on
along these U(1)s are uplifted to non-harmonic four-form fluxes. We derive the
effective four-dimensional gauged supergravity resulting from F-theory
compactifications in the presence of the Abelian gauge factors including the
effects of possible fluxes on the gauging, tadpoles and matter spectrum.Comment: 49 page
Downregulation of drug transport and metabolism in mice bearing extra-hepatic malignancies
There is increasing evidence of a systemic inflammatory response associated with malignancy, which may have an impact on both drug disposition and resistance to cytotoxic therapy. The impact of inflammation on drug disposition was studied in mice bearing a number of common tumour xenografts. C57BL/6 mice were inoculated with tumour xenografts. Hepatic expressions of Cyp3a and drug transporters were analysed at the mRNA, protein and functional levels (Cyp3a only). Circulating serum cytokines and the hepatic expression of acute phase proteins (APPs) were measured. Intratumoral levels of multidrug resistance genes were determined. Tumour xenografts elicited an inflammatory response that coincided with repression in hepatic Cyp3a11 activity and the expression of a number of hepatic drug transporters. With tumour growth, a progressive reduction in hepatic Cyp3a11 mRNA expression was seen. Conversely, an increase in the hepatic APP expression and circulating interleukin (IL)-6 levels was observed. Furthermore, a correlation was seen between increased intratumoral expression of the multidrug resistance gene, Mdr1a, and levels of circulating IL-6. Malignancy results in reduced hepatic drug disposition that correlates with an associated inflammatory response. Reduction of inflammation may improve the clinical outcome for patients receiving chemotherapeutic agents that undergo hepatic metabolism
Physiological and autonomic stress responses after prolonged sleep restriction and subsequent recovery sleep in healthy young men
Purpose Sleep restriction is increasingly common and associated with the development of health problems. We investigated how the neuroendocrine stress systems respond to prolonged sleep restriction and subsequent recovery sleep in healthy young men. Methods After two baseline (BL) nights of 8 h time in bed (TIB), TIB was restricted to 4 h per night for five nights (sleep restriction, SR, n = 15), followed by three recovery nights (REC) of 8 h TIB, representing a busy workweek and a recovery weekend. The control group (n = 8) had 8 h TIB throughout the experiment. A variety of autonomic cardiovascular parameters, together with salivary neuropeptide Y (NPY) and cortisol levels, were assessed. Results In the control group, none of the parameters changed. In the experimental group, heart rate increased from 60 +/- 1.8 beats per minute (bpm) at BL, to 63 +/- 1.1 bpm after SR and further to 65 +/- 1.8 bpm after REC. In addition, whole day low-frequency to-high frequency (LF/HF) power ratio of heart rate variability increased from 4.6 +/- 0.4 at BL to 6.0 +/- 0.6 after SR. Other parameters, including salivary NPY and cortisol levels, remained unaffected. Conclusions Increased heart rate and LF/HF power ratio are early signs of an increased sympathetic activity after prolonged sleep restriction. To reliably interpret the clinical significance of these early signs of physiological stress, a follow-up study would be needed to evaluate if the stress responses escalate and lead to more unfavourable reactions, such as elevated blood pressure and a subsequent elevated risk for cardiovascular health problems.Peer reviewe
TraR, a Homolog of a RNAP Secondary Channel Interactor, Modulates Transcription
Recent structural and biochemical studies have identified a novel control mechanism of gene expression mediated through the secondary channel of RNA Polymerase (RNAP) during transcription initiation. Specifically, the small nucleotide ppGpp, along with DksA, a RNAP secondary channel interacting factor, modifies the kinetics of transcription initiation, resulting in, among other events, down-regulation of ribosomal RNA synthesis and up-regulation of several amino acid biosynthetic and transport genes during nutritional stress. Until now, this mode of regulation of RNAP was primarily associated with ppGpp. Here, we identify TraR, a DksA homolog that mimics ppGpp/DksA effects on RNAP. First, expression of TraR compensates for dksA transcriptional repression and activation activities in vivo. Second, mutagenesis of a conserved amino acid of TraR known to be critical for DksA function abolishes its activity, implying both structural and functional similarity to DksA. Third, unlike DksA, TraR does not require ppGpp for repression of the rrnB P1 promoter in vivo and in vitro or activation of amino acid biosynthesis/transport genes in vivo. Implications for DksA/ppGpp mechanism and roles of TraR in horizontal gene transfer and virulence are discussed
Visualization and Curve-Parameter Estimation Strategies for Efficient Exploration of Phenotype Microarray Kinetics
The Phenotype MicroArray (OmniLogÂź PM) system is able to simultaneously capture a large number of phenotypes by recording an organism's respiration over time on distinct substrates. This technique targets the object of natural selection itself, the phenotype, whereas previously addressed '-omics' techniques merely study components that finally contribute to it. The recording of respiration over time, however, adds a longitudinal dimension to the data. To optimally exploit this information, it must be extracted from the shapes of the recorded curves and displayed in analogy to conventional growth curves.The free software environment R was explored for both visualizing and fitting of PM respiration curves. Approaches using either a model fit (and commonly applied growth models) or a smoothing spline were evaluated. Their reliability in inferring curve parameters and confidence intervals was compared to the native OmniLogÂź PM analysis software. We consider the post-processing of the estimated parameters, the optimal classification of curve shapes and the detection of significant differences between them, as well as practically relevant questions such as detecting the impact of cultivation times and the minimum required number of experimental repeats.We provide a comprehensive framework for data visualization and parameter estimation according to user choices. A flexible graphical representation strategy for displaying the results is proposed, including 95% confidence intervals for the estimated parameters. The spline approach is less prone to irregular curve shapes than fitting any of the considered models or using the native PM software for calculating both point estimates and confidence intervals. These can serve as a starting point for the automated post-processing of PM data, providing much more information than the strict dichotomization into positive and negative reactions. Our results form the basis for a freely available R package for the analysis of PM data
Embryology and bony malformations of the craniovertebral junction
BACKGROUND: The embryology of the bony craniovertebral junction (CVJ) is reviewed with the purpose of explaining the genesis and unusual configurations of the numerous congenital malformations in this region. Functionally, the bony CVJ can be divided into a central pillar consisting of the basiocciput and dental pivot and a two-tiered ring revolving round the central pivot, comprising the foramen magnum rim and occipital condyles above and the atlantal ring below. Embryologically, the central pillar and the surrounding rings descend from different primordia, and accordingly, developmental anomalies at the CVJ can also be segregated into those affecting the central pillar and those affecting the surrounding rings, respectively. DISCUSSION: A logical classification of this seemingly unwieldy group of malformations is thus possible based on their ontogenetic lineage, morbid anatomy, and clinical relevance. Representative examples of the main constituents of this classification scheme are given, and their surgical treatments are selectively discussed
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