3,531 research outputs found
Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles:delivery and bioactivity in pancreatic cancer cells
KRAS is mutated in >90% of pancreatic ductal adenocarcinomas. As its inactivation leads to tumour regression, mutant KRAS is considered an attractive target for anticancer drugs. In this study we report a new delivery strategy for a G4-decoy oligonucleotide that sequesters MAZ, a transcription factor essential for KRAS transcription. It is based on the use of palmitoyl-oleyl-phosphatidylcholine (POPC) liposomes functionalized with lipid-modified G4-decoy oligonucleotides and a lipid-modified cell penetrating TAT peptide. The potency of the strategy in pancreatic cancer cells is demonstrated by cell cytometry, confocal microscopy, clonogenic and qRT-PCR assays
Mechanical and dielectric relaxation spectra in seven highly viscous glass formers
Published dielectric and shear data of six molecular glass formers and one
polymer are evaluated in terms of a spectrum of thermally activated processes,
with the same barrier density for the retardation spectrum of shear and
dielectrics. The viscosity, an independent parameter of the fit, seems to be
related to the high-barrier cutoff time of the dielectric signal, in accordance
with the idea of a renewal of the relaxing entities after this critical time.
In the five cases where one can fit accurately, the temperature dependence of
the high-barrier cutoff follows the shoving model. The Johari-Goldstein peaks,
seen in four of our seven cases, are describable in terms of gaussians in the
barrier density, superimposed on the high-frequency tail of the
-process. Dielectric and shear measurements of the same substance find
the same peak positions and widths of these gaussians, but in general a
different weight.Comment: Contribution to the Ngai Fest issue of J. Non-Cryst. Solids; 8 pages,
8 figures, 30 reference
Dielectric and thermal relaxation in the energy landscape
We derive an energy landscape interpretation of dielectric relaxation times
in undercooled liquids, comparing it to the traditional Debye and
Gemant-DiMarzio-Bishop pictures. The interaction between different local
structural rearrangements in the energy landscape explains qualitatively the
recently observed splitting of the flow process into an initial and a final
stage. The initial mechanical relaxation stage is attributed to hopping
processes, the final thermal or structural relaxation stage to the decay of the
local double-well potentials. The energy landscape concept provides an
explanation for the equality of thermal and dielectric relaxation times. The
equality itself is once more demonstrated on the basis of literature data for
salol.Comment: 7 pages, 3 figures, 41 references, Workshop Disordered Systems,
Molveno 2006, submitted to Philosophical Magazin
Substitutions of red meat, poultry and fish and risk of myocardial infarction
AbstractRed meat has been suggested to be adversely associated with risk of myocardial infarction (MI), but previous studies have rarely taken replacement foods into consideration. We aimed to investigate optimal substitutions between and within the food groups of red meat, poultry and fish for MI prevention. We followed up 55 171 women and men aged 50–64 years with no known history of MI at recruitment. Diet was assessed by a validated 192-item FFQ at baseline. Adjusted Cox proportional hazard models were used to calculate hazard ratios (HR) and 95 % CI for specified food substitutions of 150 g/week. During a median follow-up time of 13·6 years, we identified 656 female and 1694 male cases. Among women, the HR for replacing red meat with fatty fish was 0·76 (95 % CI 0·64, 0·89), whereas the HR for replacing red meat with lean fish was 1·00 (95 % CI 0·89, 1·14). Similarly, replacing poultry with fatty but not lean fish was inversely associated with MI: the HR was 0·81 (95 % CI 0·67, 0·98) for fatty fish and was 1·08 (95 % CI 0·92, 1·27) for lean fish. The HR for replacing lean with fatty fish was 0·75 (95 % CI 0·60, 0·94). Replacing processed with unprocessed red meat was not associated with MI. Among men, a similar pattern was found, although the associations were not statistically significant. This study suggests that replacing red meat, poultry or lean fish with fatty fish is associated with a lower risk of MI.</jats:p
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