526 research outputs found
Evaluation of the interaction between phosphohistidine analogues and phosphotyrosine binding domains.
We have investigated the interaction of peptides containing phosphohistidine analogues and their homologues with the prototypical phosphotyrosine binding SH2 domain from the eukaryotic cell signalling protein Grb2 by using a combination of isothermal titration calorimetry and a fluorescence anisotropy competition assay. These investigations demonstrated that the triazole class of phosphohistidine analogues are capable of binding too, suggesting that phosphohistidine could potentially be detected by this class of proteins in vivo
Effect of surface modification of siliconeon Staphylococcus epidermidis adhesion and colonization
Cerebrospinal fluid (CSF) shunts for the treatment of hydrocephalus are generally made of silicone rubber. The growth of bacterial colonies on the silicone surface leads to frequent CSF shunt complications. A systematic study of the effect of the surface modification of silicone on Staphylococcus epidermidis adhesion and colonization was performed for different incubation times by means of colony counting and scanning electron microscopy (SEM). Silicone was modified with different biopolymers and silanes, including heparin, hyaluronan, octadecyltrichlorosilane (OTS), and fluoroalkylsilane (FAS) to provide a stable and biocompatible surface with different surface functional groups and degrees of hydrophobicity. The modified silicone surfaces were studied by using contact angle measurements, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). After 4 and 8 h of incubation, the FAS- and OTS-coated silicone and the hyaluronan coated OTS/silicone surfaces showed significantly reduced bacterial adhesion and colonization compared to blank silicone by both quantification methods. However, the heparin coated OTS/silicone showed significantly increased bacterial adhesion. These results indicate that the nature of the surface functional group and surface roughness determine the extent of bacterial adhesion and colonization. However, the degree of hydrophobicity of the surface did not appear to play a determining role in bacterial adhesion and colonization. Ā© 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55980/1/30952_ftp.pd
Desensitizing Inflation from the Planck Scale
A new mechanism to control Planck-scale corrections to the inflationary eta
parameter is proposed. A common approach to the eta problem is to impose a
shift symmetry on the inflaton field. However, this symmetry has to remain
unbroken by Planck-scale effects, which is a rather strong requirement on
possible ultraviolet completions of the theory. In this paper, we show that the
breaking of the shift symmetry by Planck-scale corrections can be
systematically suppressed if the inflaton field interacts with a conformal
sector. The inflaton then receives an anomalous dimension in the conformal
field theory, which leads to sequestering of all dangerous high-energy
corrections. We analyze a number of models where the mechanism can be seen in
action. In our most detailed example we compute the exact anomalous dimensions
via a-maximization and show that the eta problem can be solved using only
weakly-coupled physics.Comment: 34 pages, 3 figures
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
The Wasteland of Random Supergravities
We show that in a general \cal{N} = 1 supergravity with N \gg 1 scalar
fields, an exponentially small fraction of the de Sitter critical points are
metastable vacua. Taking the superpotential and Kahler potential to be random
functions, we construct a random matrix model for the Hessian matrix, which is
well-approximated by the sum of a Wigner matrix and two Wishart matrices. We
compute the eigenvalue spectrum analytically from the free convolution of the
constituent spectra and find that in typical configurations, a significant
fraction of the eigenvalues are negative. Building on the Tracy-Widom law
governing fluctuations of extreme eigenvalues, we determine the probability P
of a large fluctuation in which all the eigenvalues become positive. Strong
eigenvalue repulsion makes this extremely unlikely: we find P \propto exp(-c
N^p), with c, p being constants. For generic critical points we find p \approx
1.5, while for approximately-supersymmetric critical points, p \approx 1.3. Our
results have significant implications for the counting of de Sitter vacua in
string theory, but the number of vacua remains vast.Comment: 39 pages, 9 figures; v2: fixed typos, added refs and clarification
Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes
Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response.
Methods: PPARĪ±, Ī² and Ī³ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARĪ± protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARĪ± was analyzed by gel shift assay.
Results: In lymphocytes, the expression of PPARĪ± mRNA, but not of PPARĪ², was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARĪ± was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARĪ± and PPARĪ² mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARĪ³ mRNA levels were below the detection limit.
Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARĪ± may therefore contribute to the inflammatory processes that are observed in CF
Lynch syndrome: barriers to and facilitators of screening and disease management
Background
Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing.
Methods
The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management.
Results
Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers.
Conclusions
Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health
A Terminal Velocity on the Landscape: Particle Production near Extra Species Loci in Higher Dimensions
We investigate particle production near extra species loci (ESL) in a higher
dimensional field space and derive a speed limit in moduli space at weak
coupling. This terminal velocity is set by the characteristic ESL-separation
and the coupling of the extra degrees of freedom to the moduli, but it is
independent of the moduli's potential if the dimensionality of the field space
is considerably larger than the dimensionality of the loci, D >> d. Once the
terminal velocity is approached, particles are produced at a plethora of nearby
ESLs, preventing a further increase in speed via their backreaction. It is
possible to drive inflation at the terminal velocity, providing a
generalization of trapped inflation with attractive features: we find that more
than sixty e-folds of inflation for sub-Planckian excursions in field space are
possible if ESLs are ubiquitous, without fine tuning of initial conditions and
less tuned potentials. We construct a simple, observationally viable model with
a slightly red scalar power-spectrum and suppressed gravitational waves; we
comment on the presence of additional observational signatures originating from
IR-cascading and individual massive particles. We also show that
moduli-trapping at an ESL is suppressed for D >> d, hindering dynamical
selection of high-symmetry vacua on the landscape based on this mechanism.Comment: 46 pages, 6 figures. V3: typos corrected compared to JHEP version,
conclusions unchange
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