4,305 research outputs found
Stochastic switching in infinite dimensions with applications to random parabolic PDE
© 2015 Society for Industrial and Applied Mathematics.We consider parabolic PDEs with randomly switching boundary conditions. In order to analyze these random PDEs, we consider more general stochastic hybrid systems and prove convergence to, and properties of, a stationary distribution. Applying these general results to the heat equation with randomly switching boundary conditions, we find explicit formulae for various statistics of the solution and obtain almost sure results about its regularity and structure. These results are of particular interest for biological applications as well as for their significant departure from behavior seen in PDEs forced by disparate Gaussian noise. Our general results also have applications to other types of stochastic hybrid systems, such as ODEs with randomly switching right-hand sides
Sensitivity to switching rates in stochastically switched ODEs
We consider a stochastic process driven by a linear ordinary differential equation whose right-hand side switches at exponential times between a collection of different matrices. We construct planar examples that switch between two matrices where the individual matrices and the average of the two matrices are all Hurwitz (all eigenvalues have strictly negative real part), but nonetheless the process goes to infinity at large time for certain values of the switching rate. We further construct examples in higher dimensions where again the two individual matrices and their averages are all Hurwitz, but the process has arbitrarily many transitions between going to zero and going to infinity at large time as the switching rate varies. In order to construct these examples, we first prove in general that if each of the individual matrices is Hurwitz, then the process goes to zero at large time for sufficiently slow switching rate and if the average matrix is Hurwitz, then the process goes to zero at large time for sufficiently fast switching rate. We also give simple conditions that ensure the process goes to zero at large time for all switching rates. © 2014 International Press
Propagation of fluctuations in biochemical systems, I: Linear SSC networks
We investigate the propagation of random fluctuations through biochemical networks in which the number of molecules of each species is large enough so that the concentrations are well modeled by differential equations. We study the effect of network topology on the emergent properties of the reaction system by characterizing the behavior of variance as fluctuations propagate down chains and studying the effect of side chains and feedback loops. We also investigate the asymptotic behavior of the system as one reaction becomes fast relative to the others. © 2007 Springer Science+Business Media, Inc
Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres
<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs), some of which function as oncogenes or tumor suppressor genes, are involved in carcinogenesis via regulating cell proliferation and/or cell death. MicroRNA miR-34 was recently found to be a direct target of p53, functioning downstream of the p53 pathway as a tumor suppressor. miR-34 targets Notch, HMGA2, and Bcl-2, genes involved in the self-renewal and survival of cancer stem cells. The role of miR-34 in gastric cancer has not been reported previously. In this study, we examined the effects of miR-34 restoration on p53-mutant human gastric cancer cells and potential target gene expression.</p> <p>Methods</p> <p>Human gastric cancer cells were transfected with miR-34 mimics or infected with the lentiviral miR-34-MIF expression system, and validated by miR-34 reporter assay using Bcl-2 3'UTR reporter. Potential target gene expression was assessed by Western blot for proteins, and by quantitative real-time RT-PCR for mRNAs. The effects of miR-34 restoration were assessed by cell growth assay, cell cycle analysis, caspase-3 activation, and cytotoxicity assay, as well as by tumorsphere formation and growth.</p> <p>Results</p> <p>Human gastric cancer Kato III cells with miR-34 restoration reduced the expression of target genes Bcl-2, Notch, and HMGA2. Bcl-2 3'UTR reporter assay showed that the transfected miR-34s were functional and confirmed that Bcl-2 is a direct target of miR-34. Restoration of miR-34 chemosensitized Kato III cells with a high level of Bcl-2, but not MKN-45 cells with a low level of Bcl-2. miR-34 impaired cell growth, accumulated the cells in G1 phase, increased caspase-3 activation, and, more significantly, inhibited tumorsphere formation and growth.</p> <p>Conclusion</p> <p>Our results demonstrate that in p53-deficient human gastric cancer cells, restoration of functional miR-34 inhibits cell growth and induces chemosensitization and apoptosis, indicating that miR-34 may restore p53 function. Restoration of miR-34 inhibits tumorsphere formation and growth, which is reported to be correlated to the self-renewal of cancer stem cells. The mechanism of miR-34-mediated suppression of self-renewal appears to be related to the direct modulation of downstream targets Bcl-2, Notch, and HMGA2, indicating that miR-34 may be involved in gastric cancer stem cell self-renewal/differentiation decision-making. Our study suggests that restoration of the tumor suppressor miR-34 may provide a novel molecular therapy for p53-mutant gastric cancer.</p
Small inhibitor of Bcl-2, HA14-1, selectively enhanced the apoptotic effect of cisplatin by modulating Bcl-2 family members in MDA-MB-231 breast cancer cells
Inhibition or downregulation of Bcl-2 represents a new therapeutic approach to by-pass chemoresistance in cancer cells. Therefore, we explored the potential of this approach in breast cancer cells. Cisplatin and paclitaxel induced apoptosis in a dose-dependent manner in MCF-7 (drug-sensitive) and MDA-MB-231 (drug-insensitive) cells. Furthermore, when we transiently silenced Bcl-2, both cisplatin and paclitaxel induced apoptosis more than parental cells. Dose dependent induction of apoptosis by drugs was enhanced by the pre-treatment of these cells with HA14-1, a Bcl-2 inhibitor. Although the effect of cisplatin was significant on both cell lines, the effect of paclitaxel was much less potent only in MDA-MB-231 cells. To further understand the distinct role of drugs in MDA-MB-231 cells pretreated with HA14-1, caspases and Bcl-2 family proteins were studied. The apoptotic effect of cisplatin with or without HA14-1 pre-treatment is shown to be caspase-dependent. Among pro-apoptotic Bcl-2 proteins, Bax and Puma were found to be up-regulated whereas Bcl-2 and Bcl-x(L) were down-regulated when cells were pretreated with HA14-1 followed by paclitaxel or cisplatin. Enforced Bcl-2 expression in MDA-MB-231 cells abrogated the sensitizing effect of HA14-1 in cisplatin induced apoptosis. These results suggest that the potentiating effect of HA14-1 is drug and cell type specific and may not only depend on the inhibition of Bcl-2. Importantly, alteration of other pro-apoptotic or anti-apoptotic Bcl-2 family members may dictate the apoptotic response when HA14-1 is combined with chemotherapeutic drugs
A relocatable ocean model in support of environmental emergencies
During the Costa Concordia emergency case, regional, subregional, and relocatable ocean models have been used together with the oil spill model, MEDSLIK-II, to provide ocean currents forecasts, possible oil spill scenarios, and drifters trajectories simulations. The models results together with the evaluation of their performances are presented in this paper. In particular, we focused this work on the implementation of the Interactive Relocatable Nested Ocean Model (IRENOM), based on the Harvard Ocean Prediction System (HOPS), for the Costa Concordia emergency and on its validation using drifters released in the area of the accident. It is shown that thanks to the capability of improving easily and quickly its configuration, the IRENOM results are of greater accuracy than the results achieved using regional or subregional model products. The model topography, and to the initialization procedures, and the horizontal resolution are the key model settings to be configured. Furthermore, the IRENOM currents and the MEDSLIK-II simulated trajectories showed to be sensitive to the spatial resolution of the meteorological fields used, providing higher prediction skills with higher resolution wind forcing.MEDESS4MS Project; TESSA Project; MyOcean2 Projectinfo:eu-repo/semantics/publishedVersio
Grassmannian flows and applications to nonlinear partial differential equations
We show how solutions to a large class of partial differential equations with
nonlocal Riccati-type nonlinearities can be generated from the corresponding
linearized equations, from arbitrary initial data. It is well known that
evolutionary matrix Riccati equations can be generated by projecting linear
evolutionary flows on a Stiefel manifold onto a coordinate chart of the
underlying Grassmann manifold. Our method relies on extending this idea to the
infinite dimensional case. The key is an integral equation analogous to the
Marchenko equation in integrable systems, that represents the coodinate chart
map. We show explicitly how to generate such solutions to scalar partial
differential equations of arbitrary order with nonlocal quadratic
nonlinearities using our approach. We provide numerical simulations that
demonstrate the generation of solutions to
Fisher--Kolmogorov--Petrovskii--Piskunov equations with nonlocal
nonlinearities. We also indicate how the method might extend to more general
classes of nonlinear partial differential systems.Comment: 26 pages, 2 figure
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Mouse podoplanin supports adhesion and aggregation of platelets under arterial shear: a novel mechanism of haemostasis
The Podoplanin-CLEC-2 axis is critical in mice for prevention of haemorrhage in the cerebral vasculature during mid-gestation. This raises the question as to how platelets are captured by podoplanin on neuroepithelial cells in a high shear environment. In this study, we
demonstrate that mouse platelets form stable aggregates on mouse podoplanin at arterial shear through a CLEC-2 and Src kinase-dependent pathway. Adhesion and aggregation are also dependent on the platelet glycoprotein (GP) receptors, integrin αIIbβ3 and GPIb, and the feedback agonists ADP and thromboxane A2 (TxA2). CLEC-2 does not bind to von Willebrand factor (VWF) suggesting that the interaction with podoplanin is sufficient to both tether and activate platelets. Consistent with this, surface plasmon resonance
measurements reveal that mouse CLEC-2 binds to mouse podoplanin with nanomolar affinity. The present findings demonstrate a novel pathway of haemostasis in which
podoplanin supporting platelet capture and activation at arteriolar rates of shear
A meta-analytic review of stand-alone interventions to improve body image
Objective
Numerous stand-alone interventions to improve body image have been developed. The
present review used meta-analysis to estimate the effectiveness of such interventions, and
to identify the specific change techniques that lead to improvement in body image.
Methods
The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on
improving body image), (b) a control group was used, (c) participants were randomly
assigned to conditions, and (d) at least one pretest and one posttest measure of body
image was taken. Effect sizes were meta-analysed and moderator analyses were conducted.
A taxonomy of 48 change techniques used in interventions targeted at body image
was developed; all interventions were coded using this taxonomy.
Results
The literature search identified 62 tests of interventions (N = 3,846). Interventions produced
a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in
beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies
(d+ = -0.72). However, the effect size for body image was inflated by bias both within
and across studies, and was reliable but of small magnitude once corrections for bias were
applied. Effect sizes for the other outcomes were no longer reliable once corrections for
bias were applied. Several features of the sample, intervention, and methodology moderated
intervention effects. Twelve change techniques were associated with improvements in
body image, and three techniques were contra-indicated.
Conclusions
The findings show that interventions engender only small improvements in body image, and
underline the need for large-scale, high-quality trials in this area. The review identifies effective
techniques that could be deployed in future interventions
A cross-sectional study of vascular risk factors in a rural South African population : data from the Southern African Stroke Prevention Initiative (SASPI)
Background: Rural sub-Saharan Africa is at an early stage of economic and health transition. It is
predicted that the 21st century will see a serious added economic burden from non-communicable disease
including vascular disease in low-income countries as they progress through the transition. The stage of
vascular disease in a population is thought to result from the prevalence of vascular risk factors. Already
hypertension and stroke are common in adults in sub-Saharan Africa. Using a multidisciplinary approach
we aimed to assess the prevalence of several vascular risk factors in Agincourt, a rural demographic
surveillance site in South Africa.
Methods: We performed a cross sectional random sample survey of adults aged over 35 in Agincourt
(population ≈ 70 000). Participants were visited at home by a trained nurse who administered a
questionnaire, carried out clinical measurements and took a blood sample. From this we assessed
participants' history of vascular risk, blood pressure using an OMRON 705 CP monitor, waist
circumference, body mass index (BMI), ankle brachial index (ABI), and total and HDL cholesterol.
Results: 402 people (24% men) participated. There was a high prevalence of smoking in men, but the
number of cigarettes smoked was small. There was a striking difference in mean BMI between men and
women (22.8 kg/m2 versus 27.2 kg/m2), but levels of blood pressure were very similar. 43% of participants
had a blood pressure greater than 140/90 or were on anti-hypertensive treatment and 37% of participants
identified with measured high blood pressure were on pharmacological treatment. 12% of participants had
an ABI of < 0.9, sugesting the presence of sub-clinical atheroma. 25.6% of participants had a total
cholesterol level > 5 mmol/l.
Conclusion: We found a high prevalence of hypertension, obesity in women, and a suggestion of
subclinical atheroma despite relatively favourable cholesterol levels in a rural South African population.
South Africa is facing the challenge of an emerging epidemic of vascular disease. Research to establish the
social determinates of these risk factors and interventions to reduce both individual and population risk
are required
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