Overexpression of microRNA-16 declines cellular growth, proliferation and induces apoptosis in human breast cancer cells

MicroRNAs (miRNA) are a large family of small single-stranded RNA molecules found in all multicellular organisms. Early studies have been shown that miRNA are involved in cancer development and progression, and this role can be done by working as an oncogenes and tumor suppressor genes, so manipulation of this molecules can be a promising approach in cancer therapy, and experimental results represented that the modification in breast cancer phenotype is possible by miRNA expression alteration. miR-16, which is located in 13q14 chromosome, plays critical roles as a tumor suppressor by targeting several oncogenes which regulate cell cycle and apoptosis. Hence, in the present study, we investigated whether miR-16 could decline growth and survival of MCF-7 cell line as model of human breast cancer. MCF-7 cell line was infected with lentiviruses containing miR-16 precursor sequence. The effects of ectopic expression of miR-16 on breast cancer phenotype were examined by cell cycle analysis and apoptosis assays. miR-16 cytotoxicity effect was measured by the MTT assay. We showed that the miR-16 overexpression reduces Cyclin D1 and BCL2 at messenger RNA (mRNA) and protein levels in MCF-7 cell line. In addition, this is found that enforced expression of miR-16 decreases cell growth and proliferation and induces apoptosis in MCF-7 cells. In conclusion, our results revealed that upregulation of miR-16 would be a potential approach for breast cancer therapy. © 2015, The Society for In Vitro Biology

The effects of moderately fast shellular rotation on adiabatic oscillations

We investigate adiabatic oscillations for delta Scuti star models, taking into account a moderate rotation velocity ~100 \km/s. The resulting oscillation frequencies include corrections for rotation up to second order in the rotation rate including those of near degeneracy. Effects of either a uniform rotation or a rotation profile assuming local angular momentum conservation of the form Omega=Omega(r) on oscillation frequencies are compared. As expected, important differences (around 3 microHz) are obtained in the $g$ and mixed mode regions. For higher frequency p modes, differences range between 1 microHz and 3 microHz. Such differences are likely to be detectable with future space missions such as COROT, where precisions in frequency around 0.5 microHz will be reachable.Comment: A&A, in press (18 pag, 14 fig

Multifocal High-Grade Pancreatic Precursor Lesions: A Case Series and Management Recommendations

Background: The risk of developing invasive cancer in the remnant pancreas after resection of multifocal high-grade pancreatic precursor lesions is not well known. We report three patients who were followed up after resection of multifocal high-grade pancreatic intraepithelial neoplasia (PanIN)-3 or intraductal papillary mucinous neoplasia (IPMN), two of whom eventually developed invasive carcinoma. Presentation: 1) 68-year-old woman who had a laparoscopic distal pancreatectomy for multifocal mixed-type IPMN, identified as high-grade on final pathology, with negative surgical margins. During semiannual monitoring, eight years from the first surgery, the patient developed suspicious features prompting surgical resection of the body with final pathology revealing invasive ductal adenocarcinoma in the setting of IPMN. 2) 48-year-old woman who had a distal pancreatectomy for severe acute/chronic symptomatic pancreatitis, with final pathology revealing multifocal high-grade PanIN-3, with negative surgical margins. Despite semiannual monitoring, two years from the first surgery, the patient developed pancreatic adenocarcinoma with liver metastasis. 3) 55-year-old woman who had a Whipple procedure for symptomatic chronic pancreatitis, with multifocal PanIN-3 on final pathology. The patient underwent completion pancreatectomy due to symptomatology and her high-risk profile, with final pathology confirming multifocal PanIN-3. Conclusion: Multifocal high-grade dysplastic lesions of the pancreas might benefit from surgical resection

Statistical stability and limit laws for Rovella maps

We consider the family of one-dimensional maps arising from the contracting Lorenz attractors studied by Rovella. Benedicks-Carleson techniques were used by Rovella to prove that there is a one-parameter family of maps whose derivatives along their critical orbits increase exponentially fast and the critical orbits have slow recurrent to the critical point. Metzger proved that these maps have a unique absolutely continuous ergodic invariant probability measure (SRB measure). Here we use the technique developed by Freitas and show that the tail set (the set of points which at a given time have not achieved either the exponential growth of derivative or the slow recurrence) decays exponentially fast as time passes. As a consequence, we obtain the continuous variation of the densities of the SRB measures and associated metric entropies with the parameter. Our main result also implies some statistical properties for these maps.Comment: 1 figur

MicroRNA-129-1 acts as tumour suppressor and induces cell cycle arrest of GBM cancer cells through targeting IGF2BP3 and MAPK1

Background MicroRNA-129-1 (miR-129-1) seems to behave as a tumour suppressor since its decreased expression is associated with different tumours such as glioblastoma multiforme (GBM). GBM is the most common form of brain tumours originating from glial cells. The impact of miR-129-1 downregulation on GBM pathogenesis has yet to be elucidated. Methods MiR-129-1 was overexpressed in GBM cells, and its effect on proliferation was investigated by cell cycle assay. MiR-129-1 predicted targets (CDK6, IGF1, HDAC2, IGF2BP3 and MAPK1) were also evaluated by western blot and luciferase assay. Results Restoration of miR-129-1 reduced cell proliferation and induced G1 accumulation, significantly. Several functional assays confirmed IGF2BP3, MAPK1 and CDK6 as targets of miR-129-1. Despite the fact that IGF1 expression can be suppressed by miR-129-1, through 30-untranslated region complementary sequence, we could not find any association between IGF1 expression and GBM. MiR-129-1 expression inversely correlates with CDK6, IGF2BP3 and MAPK1 in primary clinical samples. Conclusion This is the first study to propose miR129-1 as a negative regulator of IGF2BP3 and MAPK1 and also a cell cycle arrest inducer in GBM cells. Our data suggests miR-129-1 as a potential tumour suppressor and presents a rationale for the use of miR-129-1 as a novel strategy to improve treatment response in GBM

Exploiting Symmetry and Heuristic Demonstrations in Off-policy Reinforcement Learning for Robotic Manipulation

Reinforcement learning demonstrates significant potential in automatically building control policies in numerous domains, but shows low efficiency when applied to robot manipulation tasks due to the curse of dimensionality. To facilitate the learning of such tasks, prior knowledge or heuristics that incorporate inherent simplification can effectively improve the learning performance. This paper aims to define and incorporate the natural symmetry present in physical robotic environments. Then, sample-efficient policies are trained by exploiting the expert demonstrations in symmetrical environments through an amalgamation of reinforcement and behavior cloning, which gives the off-policy learning process a diverse yet compact initiation. Furthermore, it presents a rigorous framework for a recent concept and explores its scope for robot manipulation tasks. The proposed method is validated via two point-to-point reaching tasks of an industrial arm, with and without an obstacle, in a simulation experiment study. A PID controller, which tracks the linear joint-space trajectories with hard-coded temporal logic to produce interim midpoints, is used to generate demonstrations in the study. The results of the study present the effect of the number of demonstrations and quantify the magnitude of behavior cloning to exemplify the possible improvement of model-free reinforcement learning in common manipulation tasks. A comparison study between the proposed method and a traditional off-policy reinforcement learning algorithm indicates its advantage in learning performance and potential value for applications