94 research outputs found
Anti-tumor effects of ketogenic diets in mice: A meta-analysis
Background: Currently ketogenic diets (KDs) are hyped as an anti-tumor intervention aimed at exploiting the metabolic abnormalities of cancer cells. However, while data in humans is sparse, translation of murine tumor models to the clinic is further hampered by small sample sizes, heterogeneous settings and mixed results concerning tumor growth retardation. The aim was therefore to synthesize the evidence for a growth inhibiting effect of KDs when used as a monotherapy in mice. Methods: We conducted a Bayesian random effects meta-analysis on all studies assessing the survival (defined as the time to reach a pre-defined endpoint such as tumor volume) of mice on an unrestricted KD compared to a high carbohydrate standard diet (SD). For 12 studies meeting the inclusion criteria either a mean survival time ratio (MR) or hazard ratio (HR) between the KD and SD groups could be obtained. The posterior estimates for the MR and HR averaged over four priors on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior density interval (HPDI) = [0.73, 0.97]) and HR = 0.55 (95% HPDI = [0.26, 0.87]), indicating a significant overall benefit of the KD in terms of prolonged mean survival times and reduced hazard rate. All studies that used a brain tumor model also chose a late starting point for the KD (at least one day after tumor initiation) which accounted for 26% of the heterogeneity. In this subgroup the KD was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04]). Conclusions: There was an overall tumor growth delaying effect of unrestricted KDs in mice. Future experiments should aim at differentiating the effects of KD timing versus tumor location, since external evidence is currently consistent with an influence of both of these factors
Reorientational relaxation of a linear probe molecule in a simple glassy liquid
Within the mode-coupling theory (MCT) for the evolution of structural
relaxation in glass-forming liquids, correlation functions and susceptibility
spectra are calculated characterizing the rotational dynamics of a top-down
symmetric dumbbell molecule, consisting of two fused hard spheres immersed in a
hard-sphere system. It is found that for sufficiently large dumbbell
elongations, the dynamics of the probe molecule follows the same universal
glass-transition scenario as known from the MCT results of simple liquids. The
-relaxation process of the angular-index-j=1 response is stronger,
slower and less stretched than the one for j=2, in qualitative agreement with
results found by dielectric-loss and depolarized-light-scattering spectroscopy
for some supercooled liquids. For sufficiently small elongations, the
reorientational relaxation occurs via large-angle flips, and the standard
scenario for the glass-transition dynamics is modified for odd-j responses due
to precursor phenomena of a nearby type-A MCT transition. In this case, a major
part of the relaxation outside the transient regime is described qualitatively
by the -relaxation scaling laws, while the -relaxation scaling
law is strongly disturbed.Comment: 40 pages. 10 figures as GIF-files, to be published in Phys. Rev.
Test of mode coupling theory for a supercooled liquid of diatomic molecules.I. Translational degrees of freedom
A molecular dynamics simulation is performed for a supercooled liquid of
rigid diatomic molecules. The time-dependent self and collective density
correlators of the molecular centers of mass are determined and compared with
the predictions of the ideal mode coupling theory (MCT) for simple liquids.
This is done in real as well as in momentum space. One of the main results is
the existence of a unique transition temperature T_c, where the dynamics
crosses over from an ergodic to a quasi-nonergodic behavior. The value for T_c
agrees with that found earlier for the orientational dynamics within the error
bars. In the beta- regime of MCT the factorization of space- and time
dependence is satisfactorily fulfilled for both types of correlations. The
first scaling law of ideal MCT holds in the von Schweidler regime, only, since
the validity of the critical law can not be confirmed, due to a strong
interference with the microscopic dynamics. In this first scaling regime a
consistent description within ideal MCT emerges only, if the next order
correction to the asymptotic law is taken into account. This correction is
almost negligible for q=q_max, the position of the main peak in the static
structure factor S(q), but becomes important for q=q_min, the position of its
first minimum. The second scaling law, i.e. the time-temperature superposition
principle, holds reasonably well for the self and collective density
correlators and different values for q. The alpha-relaxation times tau_q^(s)
and tau_q follow a power law in T-T_c over 2 -- 3 decades. The corresponding
exponent gamma is weakly q-dependent and is around 2.55. This value is in
agreement with the one predicted by MCT from the value of the von Schweidler
exponent but at variance with the corresponding exponent gammaComment: 14 pages of RevTex, 19 figure
Propylene Carbonate Reexamined: Mode-Coupling Scaling without Factorisation ?
The dynamic susceptibility of propylene carbonate in the moderately viscous
regime above is reinvestigated by incoherent neutron and
depolarised light scattering, and compared to dielectric loss and solvation
response. Depending on the strength of relaxation, a more or less
extended scaling regime is found. Mode-coupling fits yield consistently
and K, although different positions of the
susceptibility minimum indicate that not all observables have reached the
universal asymptotics
Static and Dynamic Properties of a Viscous Silica Melt Molecular Dynamics Computer Simulations
We present the results of a large scale molecular dynamics computer
simulation in which we investigated the static and dynamic properties of a
silica melt in the temperature range in which the viscosity of the system
changes from O(10^-2) Poise to O(10^2) Poise. We show that even at temperatures
as high as 4000 K the structure of this system is very similar to the random
tetrahedral network found in silica at lower temperatures. The temperature
dependence of the concentration of the defects in this network shows an
Arrhenius law. From the partial structure factors we calculate the neutron
scattering function and find that it agrees very well with experimental neutron
scattering data. At low temperatures the temperature dependence of the
diffusion constants shows an Arrhenius law with activation energies which
are in very good agreement with the experimental values. With increasing
temperature we find that this dependence shows a cross-over to one which can be
described well by a power-law, D\propto (T-T_c)^gamma. The critical temperature
T_c is 3330 K and the exponent gamma is close to 2.1. Since we find a similar
cross-over in the viscosity we have evidence that the relaxation dynamics of
the system changes from a flow-like motion of the particles, as described by
the ideal version of mode-coupling theory, to a hopping like motion. We show
that such a change of the transport mechanism is also observed in the product
of the diffusion constant and the life time of a Si-O bond, or the space and
time dependence of the van Hove correlation functions.Comment: 30 pages of Latex, 14 figure
Molecular mode-coupling theory applied to a liquid of diatomic molecules
We study the molecular mode coupling theory for a liquid of diatomic
molecules. The equations for the critical tensorial nonergodicity parameters
and the critical amplitudes of the - relaxation
are solved up to a cut off = 2 without any
further approximations.
Here are indices of spherical harmonics. Contrary to previous studies,
where additional approximations were applied, we find in agreement with
simulations, that all molecular degrees of freedom vitrify at a single
temperature . The theoretical results for the non ergodicity parameters
and the critical amplitudes are compared with those from simulations. The
qualitative agreement is good for all molecular degrees of freedom. To study
the influence of the cut off on the non ergodicity parameter, we also calculate
the non ergodicity parameters for an upper cut off . In addition we
also propose a new method for the calculation of the critical nonergodicity
parameterComment: 27 pages, 17 figure
The mean-squared displacement of a molecule moving in a glassy system
The mean-squared displacement (MSD) of a hard sphere and of a dumbbell
molecule consisting of two fused hard spheres immersed in a dense hard-sphere
system is calculated within the mode-coupling theory for ideal liquid-glass
transitions. It is proven that the velocity correlator, which is the second
time derivative of the MSD, is the negative of a completely monotone function
for times within the structural-relaxation regime. The MSD is found to exhibit
a large time interval for structural relaxation prior to the onset of the
-process which cannot be described by the asymptotic formulas for the
mode-coupling-theory-bifurcation dynamics. The -process for molecules
with a large elongation is shown to exhibit an anomalously wide cross-over
interval between the end of the von-Schweidler decay and the beginning of
normal diffusion. The diffusivity of the molecule is predicted to vary
non-monotonically as function of its elongation.Comment: 18 pages, 12 figures, Phys. Rev. E, in prin
Dynamics of the rotational degrees of freedom in a supercooled liquid of diatomic molecules
Using molecular dynamics computer simulations, we investigate the dynamics of
the rotational degrees of freedom in a supercooled system composed of rigid,
diatomic molecules. The interaction between the molecules is given by the sum
of interaction-site potentials of the Lennard-Jones type. In agreement with
mode-coupling theory (MCT), we find that the relaxation times of the
orientational time correlation functions C_1^(s), C_2^(s) and C_1 show at low
temperatures a power-law with the same critical temperature T_c, and which is
also identical to the critical temperature for the translational degrees of
freedom. In contrast to MCT we find, however, that for these correlators the
time-temperature superposition principle does not hold well and that also the
critical exponent gamma depends on the correlator. We also study the
temperature dependence of the rotational diffusion constant D_r and demonstrate
that at high temperatures D_r is proportional to the translational diffusion
constant D and that when the system starts to become supercooled the former
shows an Arrhenius behavior whereas the latter exhibits a power-law dependence.
We discuss the origin for the difference in the temperature dependence of D (or
the relaxation times of C_l^(s) and D_r. Finally we present results which show
that at low temperatures 180 degree flips of the molecule are an important
component of the relaxation dynamics for the orientational degrees of freedom.Comment: 17 pages of RevTex, 12 figure
Broadband Dielectric Spectroscopy on Glass-Forming Propylene Carbonate
Dielectric spectroscopy covering more than 18 decades of frequency has been
performed on propylene carbonate in its liquid and supercooled-liquid state.
Using quasi-optic submillimeter and far-infrared spectroscopy the dielectric
response was investigated up to frequencies well into the microscopic regime.
We discuss the alpha-process whose characteristic timescale is observed over 14
decades of frequency and the excess wing showing up at frequencies some three
decades above the peak frequency. Special attention is given to the
high-frequency response of the dielectric loss in the crossover regime between
alpha-peak and boson-peak. Similar to our previous results in other glass
forming materials we find evidence for additional processes in the crossover
regime. However, significant differences concerning the spectral form at high
frequencies are found. We compare our results to the susceptibilities obtained
from light scattering and to the predictions of various models of the glass
transition.Comment: 13 pages, 9 figures, submitted to Phys. Rev.
Increased tartrate-resistant acid phosphatase (TRAP) expression in malignant breast, ovarian and melanoma tissue: an investigational study
BACKGROUND: Tartrate-resistant acid phosphatase (TRAP) is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies. METHODS: TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells. RESULTS: A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines. CONCLUSION: Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies
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