Tumour suppressor function of MDA-7/IL-24 in human breast cancer

Introduction Melanoma differentiation associated gene-7 (MDA-7), also known as interleukin (IL)-24, is a tumour suppressor gene associated with differentiation, growth and apoptosis. However, the mechanisms underlying its anti-neoplastic activity, tumour-specificity and efficacy across a spectrum of human cancers have yet to be fully elucidated. In this study, the biological impact of MDA-7 on the behavior of breast cancer (BC) cells is evaluated. Furthermore, mRNA expression of MDA-7 is assessed in a cohort of women with BC and correlated with established pathological parameters and clinical outcome. Methods The human BC cell line MDA MB-231 was used to evaluate the in-vitro impact of recombinant human (rh)-MDA-7 on cell growth and motility, using a growth assay, wounding assay and electric cell impedance sensing (ECIS). Localisation of MDA-7 in mammary tissues was assessed with standard immuno-histochemical methodology. BC tissues (n = 127) and normal tissues (n = 33) underwent RNA extraction and reverse transcription, MDA-7 transcript levels were determined using real-time quantitative PCR. Transcript levels were analyzed against tumour size, grade, oestrogen receptor (ER) status, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI) and clinical outcome over a 10 year follow-up period. Results Exposure to rh-MDA-7 significantly reduced wound closure rates for human BC cells in-vitro. The ECIS model demonstrated a significantly reduced motility and migration following rh-MDA-7 treatment (p = 0.024). Exposure to rh-MDA-7 was only found to exert a marginal effect on growth. Immuno-histochemical staining of human breast tissues revealed substantially greater MDA-7 positivity in normal compared to cancer cells. Significantly lower MDA-7 transcript levels were identified in those predicted to have a poorer prognosis by the NPI (p = 0.049) and those with node positive tumours. Significantly lower expression was also noted in tumours from patients who died of BC compared to those who remained disease free (p = 0.035). Low levels of MDA-7 were significantly correlated with a shorter disease free survival (mean = 121.7 vs. 140.4 months, p = 0.0287) on Kaplan-Meier survival analysis. Conclusion MDA-7 significantly inhibits the motility and migration of human BC cells in-vitro. MDA-7 expression is substantially reduced in malignant breast tissue and low transcript levels are significantly associated with unfavourable pathological parameters, including nodal positivity; and adverse clinical outcomes including poor prognosis and shorter disease free survival. MDA-7 offers utility as a prognostic marker and potential for future therapeutic strategies

Nonlinear Dynamics of Silicon Nanowire Resonator Considering Nonlocal Effect

In this work, nonlinear dynamics of silicon nanowire resonator considering nonlocal effect has been investigated. For the first time, dynamical parameters (e.g., resonant frequency, Duffing coefficient, and the damping ratio) that directly influence the nonlinear dynamics of the nanostructure have been derived. Subsequently, by calculating their response with the varied nonlocal coefficient, it is unveiled that the nonlocal effect makes more obvious impacts at the starting range (from zero to a small value), while the impact of nonlocal effect becomes weaker when the nonlocal term reaches to a certain threshold value. Furthermore, to characterize the role played by nonlocal effect in exerting influence on nonlinear behaviors such as bifurcation and chaos (typical phenomena in nonlinear dynamics of nanoscale devices), we have calculated the Lyapunov exponents and bifurcation diagram with and without nonlocal effect, and results shows the nonlocal effect causes the most significant effect as the device is at resonance. This work advances the development of nanowire resonators that are working beyond linear regime

The effect of spiritual healing on in vitro tumour cell proliferation and viability – an experimental study

Alternative treatments such as spiritual healing and prayer are increasingly popular, especially among patients with life-threatening diseases such as cancer. According to theories of spiritual healing, this intervention is thought to influence living cells and organisms independently of the recipient's conscious awareness of the healer's intention. The aim of this study was to test the hypothesis that spiritual healing will reduce proliferation and viability of two cancer cell lines in vitro. Three controlled experiments were conducted with three different healers and randomised allocation of cells to five different doses of healing or control. Researchers conducting the assays and statistical analyses were blinded to the experimental conditions. Main outcome measures were MTT viability, 3H-thymidine incorporation and counts of an adherent human breast cancer cell line (MCF-7), and a nonadherent mouse B-lymphoid cell line (HB-94). Analyses of variance (ANOVAs) revealed no significant main or dose-related effects of spiritual healing compared to controls for either of the two cell lines or any of the assays (P-values between 0.09 and 0.96). When comparing healing and control across all three experimental days, doses, assays, and cells, 34 (51.6%) of 66 independent comparisons showed differences in the hypothesised direction (P=0.90). The average effect size across cell lines, days, assays, and doses approached zero (Cohen's d=−0.01). The results do not support previous reports of beneficial effects of spiritual healing on malignant cell growth in vitro. Reported beneficial effects of spiritual healing on the well-being of cancer patients seem more likely to be mediated by psychosocial and psychophysiological effects of the healer–patient relationship

Effects of Crystalline Anisotropy and Indenter Size on Nanoindentation by Multiscale Simulation

Nanoindentation processes in single crystal Ag thin film under different crystallographic orientations and various indenter widths are simulated by the quasicontinuum method. The nanoindentation deformation processes under influences of crystalline anisotropy and indenter size are investigated about hardness, load distribution, critical load for first dislocation emission and strain energy under the indenter. The simulation results are compared with previous experimental results and Rice-Thomson (R-T) dislocation model solution. It is shown that entirely different dislocation activities are presented under the effect of crystalline anisotropy during nanoindentation. The sharp load drops in the load–displacement curves are caused by the different dislocation activities. Both crystalline anisotropy and indenter size are found to have distinct effect on hardness, contact stress distribution, critical load for first dislocation emission and strain energy under the indenter. The above quantities are decreased at the indenter into Ag thin film along the crystal orientation with more favorable slip directions that easy trigger slip systems; whereas those will increase at the indenter into Ag thin film along the crystal orientation with less or without favorable slip directions that hard trigger slip systems. The results are shown to be in good agreement with experimental results and R-T dislocation model solution

A Survey on the Krein-von Neumann Extension, the corresponding Abstract Buckling Problem, and Weyl-Type Spectral Asymptotics for Perturbed Krein Laplacians in Nonsmooth Domains

In the first (and abstract) part of this survey we prove the unitary equivalence of the inverse of the Krein--von Neumann extension (on the orthogonal complement of its kernel) of a densely defined, closed, strictly positive operator, $S\geq \varepsilon I_{\mathcal{H}}$ for some $\varepsilon >0$ in a Hilbert space $\mathcal{H}$ to an abstract buckling problem operator. This establishes the Krein extension as a natural object in elasticity theory (in analogy to the Friedrichs extension, which found natural applications in quantum mechanics, elasticity, etc.). In the second, and principal part of this survey, we study spectral properties for $H_{K,\Omega}$, the Krein--von Neumann extension of the perturbed Laplacian $-\Delta+V$ (in short, the perturbed Krein Laplacian) defined on $C^\infty_0(\Omega)$, where $V$ is measurable, bounded and nonnegative, in a bounded open set $\Omega\subset\mathbb{R}^n$ belonging to a class of nonsmooth domains which contains all convex domains, along with all domains of class $C^{1,r}$, $r>1/2$.Comment: 68 pages. arXiv admin note: extreme text overlap with arXiv:0907.144

Predictors of well child care adherence over time in a cohort of urban Medicaid-eligible infants

<p>Abstract</p> <p>Background</p> <p>Changes in well child care (WCC) adherence over time have not previously been examined. Our objective is to describe adherence rates to WCC over time in a low-income urban population of infants 0-24 months of age, and to identify predictors of WCC adherence in this population.</p> <p>Methods</p> <p>This is a secondary analysis of a cohort of Medicaid-eligible children followed from birth to 2 years between 2005 and 2008 with structured telephone surveys to assess maternal well-being, social support, and household and demographic information. For the 260 children attending 4 urban pediatric practices, WCC adherence was assessed based on visit data abstracted from electronic medical records. A random-intercept mixed effects logit model clustered on subject was used.</p> <p>Results</p> <p>92% of the mothers were African-American, 27% had not finished high school, 87% were single, and 43% earned < $500/month; mean age was 23. WCC adherence decreased from 88% at 6 months to 47% (12 mo), 44% (18 mo), and 67% (24 mo). The difference across time periods was statistically significant (p < 0.001). Married (OR 1.71, p = 0.02) and primiparous (OR 1.89, p < 0.001) mothers had significantly greater odds of adherence, along with women who reported having been adherent to prenatal care visits (OR 1.49, p = 0.03) and those with the lowest household income (OR 1.40, p = 0.03).</p> <p>Conclusions</p> <p>Maternal education efforts should emphasize the importance of establishing WCC, especially for mothers of more than one child. Further studies using larger, more broadly defined populations are needed to confirm our findings that efforts to increase WCC adherence should be intensified after 6 months of age, particularly for children at higher risk.</p

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table