73 research outputs found
Charmed Meson Production in Deep Inelastic Scattering
Charmed meson production in semi-inclusive deep inelastic scattering is
investigated in the color dipole formalism. The transverse momentum
distributions are calculated. We find good agreement with the H1 data using a
hard fragmentation function.Comment: 24 pages, 10 figure
Salt-induced changes of colloidal interactions in critical mixtures
We report on salt-dependent interaction potentials of a single charged
particle suspended in a binary liquid mixture above a charged wall. For
symmetric boundary conditions (BC) we observe attractive particle-wall
interaction forces which are similar to critical Casimir forces previously
observed in salt-free mixtures. However, in case of antisymmetric BC we find a
temperature-dependent crossover from attractive to repulsive forces which is in
strong contrast to salt-free conditions. Additionally performed small-angle
x-ray scattering experiments demonstrate that the bulk critical fluctuations
are not affected by the addition of salt. This suggests that the observed
crossover can not be attributed alone to critical Casimir forces. Instead our
experiments point towards a possible coupling between the ionic distributions
and the concentration profiles in the binary mixture which then affects the
interaction potentials in such systems.Comment: 5 pages, 4 Figure
Universality of the thermodynamic Casimir effect
Recently a nonuniversal character of the leading spatial behavior of the
thermodynamic Casimir force has been reported [X. S. Chen and V. Dohm, Phys.
Rev. E {\bf 66}, 016102 (2002)]. We reconsider the arguments leading to this
observation and show that there is no such leading nonuniversal term in systems
with short-ranged interactions if one treats properly the effects generated by
a sharp momentum cutoff in the Fourier transform of the interaction potential.
We also conclude that lattice and continuum models then produce results in
mutual agreement independent of the cutoff scheme, contrary to the
aforementioned report. All results are consistent with the {\em universal}
character of the Casimir force in systems with short-ranged interactions. The
effects due to dispersion forces are discussed for systems with periodic or
realistic boundary conditions. In contrast to systems with short-ranged
interactions, for one observes leading finite-size contributions
governed by power laws in due to the subleading long-ranged character of
the interaction, where is the finite system size and is the
correlation length.Comment: 11 pages, revtex, to appear in Phys. Rev. E 68 (2003
Critical adsorption on curved objects
A systematic fieldtheoretic description of critical adsorption on curved
objects such as spherical or rodlike colloidal particles immersed in a fluid
near criticality is presented. The temperature dependence of the corresponding
order parameter profiles and of the excess adsorption are calculated
explicitly. Critical adsorption on elongated rods is substantially more
pronounced than on spherical particles. It turns out that, within the context
of critical phenomena in confined geometries, critical adsorption on a
microscopically thin `needle' represents a distinct universality class of its
own. Under favorable conditions the results are relevant for the flocculation
of colloidal particles.Comment: 52 pages, 10 figure
Critical adsorption near edges
Symmetry breaking surface fields give rise to nontrivial and long-ranged
order parameter profiles for critical systems such as fluids, alloys or magnets
confined to wedges. We discuss the properties of the corresponding universal
scaling functions of the order parameter profile and the two-point correlation
function and determine the critical exponents eta_parallel and
eta_perpendicular for the so-called normal transition.Comment: 22 pages, 5 figures, accepted for publication in PR
Susceptibility to hormone-mediated cancer is reflected by different tick rates of the epithelial and general epigenetic clock
Background
A variety of epigenetic clocks utilizing DNA methylation changes have been developed; these clocks are either tissue-independent or designed to predict chronological age based on blood or saliva samples. Whether discordant tick rates between tissue-specific and general epigenetic clocks play a role in health and disease has not yet been explored.
Results
Here we analyze 1941 cervical cytology samples, which contain a mixture of hormone-sensitive cervical epithelial cells and immune cells, and develop the WID general clock (Women’s IDentification of risk), an epigenetic clock that is shared by epithelial and immune cells and optimized for cervical samples. We then develop the WID epithelial clock and WID immune clock, which define epithelial- and immune-specific clocks, respectively. We find that the WID-relative-epithelial-age (WID-REA), defined as the difference between the epithelial and general clocks, is significantly reduced in cervical samples from pre-menopausal women with breast cancer (OR 2.7, 95% CI 1.28-5.72). We find the same effect in normal breast tissue samples from pre-menopausal women at high risk of breast cancer and show that potential risk reducing anti-progesterone drugs can reverse this. In post-menopausal women, this directionality is reversed. Hormone replacement therapy consistently leads to a significantly lower WID-REA in cancer-free women, but not in post-menopausal women with breast or ovarian cancer.
Conclusions
Our findings imply that there are multiple epigenetic clocks, many of which are tissue-specific, and that the differential tick rate between these clocks may be an informative surrogate measure of disease risk.publishedVersio
The Influence of Concentration and Temperature on the Formation of γ-Oryzanol + β-Sitosterol Tubules in Edible Oil Organogels
The gelation process of mixtures of γ-oryzanol and sitosterol structurants in sunflower oil was studied using light scattering, rheology, and micro-scanning calorimetry (Micro-DSC). The relation between temperature and the critical aggregation concentration (CAC) of tubule formation of γ-oryzanol and sitosterol was determined using these techniques. The temperature dependence of the CAC was used to estimate the binding energy and enthalpic and entropic contribution to the tubular formation process. The binding energy calculated at the corresponding temperatures and CACs were relatively low, in order of 2 RT (4.5 kJ mol−1), which is in accord with the reversibility of the tubular formation process. The formation of the tubules was associated with negative (exothermic) enthalpy change (ΔH0) compared with positive entropy term (−T ΔS0 >0), indicating that the aggregation into tubules is an enthalpy-driven process. The oryzanol–sitosterol ratio affected the aggregation process; solutions with ratio of (60 oryzanol–40 sitosterol) started aggregation at higher temperature compared with other ratios
Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women
Background:
Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion of luminal progenitor cells, leading to the development of poor-prognostic breast cancers. However, it is not known if antagonising progesterone can prevent breast cancers in humans. We suggest that targeting progesterone signalling could be a means of reducing features which are known to promote breast cancer formation.
Methods:
In healthy premenopausal women with and without a BRCA mutation we studied (i) estrogen and progesterone levels in saliva over an entire menstrual cycle (n = 20); (ii) cancer-free normal breast-tissue from a control population who had no family or personal history of breast cancer and equivalently from BRCA1/2 mutation carriers (n = 28); triple negative breast cancer (TNBC) biopsies and healthy breast tissue taken from sites surrounding the TNBC in the same individuals (n = 14); and biopsies of ER+ve/PR+ve stage T1–T2 cancers and healthy breast tissue taken from sites surrounding the cancer in the same individuals (n = 31); and (iii) DNA methylation and DNA mutations in normal breast tissue (before and after treatment) from clinical trials that assessed the potential preventative effects of vitamins and antiprogestins (mifepristone and ulipristal acetate; n = 44).
Results:
Daily levels of progesterone were higher throughout the menstrual cycle of BRCA1/2 mutation carriers, raising the prospect of targeting progesterone signalling as a means of cancer risk reduction in this population. Furthermore, breast field cancerization DNA methylation signatures reflective of (i) the mitotic age of normal breast epithelium and (ii) the proportion of luminal progenitor cells were increased in breast cancers, indicating that luminal progenitor cells with elevated replicative age are more prone to malignant transformation. The progesterone receptor antagonist mifepristone reduced both the mitotic age and the proportion of luminal progenitor cells in normal breast tissue of all control women and in 64% of BRCA1/2 mutation carriers. These findings were validated by an alternate progesterone receptor antagonist, ulipristal acetate, which yielded similar results. Importantly, mifepristone reduced both the TP53 mutation frequency as well as the number of TP53 mutations in mitotic-age-responders.
Conclusions:
These data support the potential usage of antiprogestins for primary prevention of poor-prognostic breast cancers
6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 is essential for p53-null cancer cells.
The bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 (PFKFB4) controls metabolic flux through allosteric regulation of glycolysis. Here we show that p53 regulates the expression of PFKFB4 and that p53-deficient cancer cells are highly dependent on the function of this enzyme. We found that p53 downregulates PFKFB4 expression by binding to its promoter and mediating transcriptional repression via histone deacetylases. Depletion of PFKFB4 from p53-deficient cancer cells increased levels of the allosteric regulator fructose-2,6-bisphosphate, leading to increased glycolytic activity but decreased routing of metabolites through the oxidative arm of the pentose-phosphate pathway. PFKFB4 was also required to support the synthesis and regeneration of nicotinamide adenine dinucleotide phosphate (NADPH) in p53-deficient cancer cells. Moreover, depletion of PFKFB4-attenuated cellular biosynthetic activity and resulted in the accumulation of reactive oxygen species and cell death in the absence of p53. Finally, silencing of PFKFB4-induced apoptosis in p53-deficient cancer cells in vivo and interfered with tumour growth. These results demonstrate that PFKFB4 is essential to support anabolic metabolism in p53-deficient cancer cells and suggest that inhibition of PFKFB4 could be an effective strategy for cancer treatment.Cancer Research UK; German Cancer Aid (grant 111917); German Research Foundation (FOR 2314); CRUK-EPSRC Imaging Centre in Cambridge and Manchester (grant 16465
Impact of opioid rescue medication for breakthrough pain on the efficacy and tolerability of long-acting opioids in patients with chronic non-malignant pain
There is little evidence that short-acting opioids as rescue medication for breakthrough pain is an optimal long-term treatment strategy in chronic non-malignant pain. We compared clinical studies of long-acting opioids that allowed short-acting opioid rescue medication with those that did not, to determine the impact of opioid rescue medication use on the analgesic efficacy and tolerability of chronic opioid therapy in patients with chronic non-malignant pain.
We searched MEDLINE (1950 to July 2006) and EMBASE (1974 to July 2006) using terms for chronic non-malignant pain and long-acting opioids. Independent review of the search results identified 48 studies that met the study selection criteria. The effect of opioid rescue medication on analgesic efficacy and the incidence of common opioid-related side-effects were analysed using meta-regression.
After adjusting for potentially confounding variables (study design and type of opioid), the difference in analgesic efficacy between the 'rescue' and the 'no rescue' studies was not significant, with regression coefficients close to 0 and 95% confidence intervals that excluded an effect of more than 18 points on a 0-100 scale in each case. There was also no significant difference between the 'rescue' and the 'no rescue' studies for the incidence of nausea, constipation, or somnolence in both the unadjusted and the adjusted analyses.
We found no evidence that rescue medication with short-acting opioids for breakthrough pain affects analgesic efficacy of long-acting opioids or the incidence of common opioid-related side-effects among chronic non-malignant pain patients
- …