A METHOD FOR DETECTING OPTIMAL SPLITS OVER TIME IN SURVIVAL ANALYSIS USING TREE-STRUCTURED MODELS

One of the most popular uses for tree-based methods is in survival analysis for censored time data where the goal is to identify factors that are predictive of survival. Tree-based methods, due to their ability to identify subgroups in a hierarchical manner, can sometimes provide a useful alternative to Cox's proportional hazards model (1972) for the exploration of survival data. Since the data are partitioned into approximately homogeneous groups, Kaplan-Meier estimators can be used to compare prognosis between the groups presented by "nodes" in the tree. The demand for tree-based methods comes from clinical studies where the investigators are interested in grouping patients with differing prognoses. Tree-based methods are usually conducted at landmark time points, for example, five-year overall survival, but the effects of some covariates might be attenuated or increased at some other landmark time point. In some applications, it may be of interest to also determine the time point with respect to the outcome interest where the greatest discrimination between subgroups occurs. Consequently, by using a conventional approach, the time point at which the discrimination is the greatest might be missed. To remediate this potential problem, we propose a tree-structure method that will split based on the potential time-varying effects of the covariates. Accordingly, with our method, we find the best point of discrimination of a covariate with respect to not only a particular value of that covariate but also to the time when the endpoint of interest is observed. We analyze survival data from the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-09 to demonstrate our method. Simulations are used to assess the statistical properties of this proposed methodology.We propose a new method in survival analysis, which is an area of statistics that is commonly used to assess prognoses of patients or participants in large public health studies. Our proposed method has public health significance because it could potentially facilitate a more refined assessment of the effect of biological and clinical markers on the survival times of different patient populations

Can selenium supplementation modify oxidative stress in-vitro?

Two thirds of the UK population are either overweight or obese (body mass index (BMI) 25-29.9 and >30 kg/m2 respectively) and are typically characterised by systemic oxidative stress (OS); deemed to play a key role in cardiovascular disease (CVD) development. OS results from chronically high reactive oxidative species (ROS) formation and reduced antioxidant status. OS plays a key role in CVD development by initiating atherosclerosis (fatty plaque accumulation within the arterial walls); therefore obese individuals are at increased risk of atherosclerosis development. Increased monocyte ROS generation instigates atherosclerotic plaque formation by increasing the recruitment, binding and transmigration of monocytes across arterial endothelial cells and into the arterial wall. An increased dietary antioxidant intake or up-regulation of endogenous antioxidant enzymes may counteract this OS state and therefore lower CVD risk. Selenium is an essential dietary micronutrient incorporated within the catalytic site of endogenous antioxidant Glutathione Peroxidase (GPx) enzymes, which protect cells from OS and consequent cell damage. There is, however, a lack of knowledge concerning the effect of selenium supplementation in an OS state representative of sedentary overweight/obese individuals. The aim of this work was to investigate the ability of selenium supplementation to modify monocyte cell viability/ROS production under OS. ITEM WAS A POSTER PRESENTATION AT 1ST ANNUAL MEETING OF THE SCOTTISH SOCIETY OF CYTOMICS (SCC) 2014. TRANSLATIONAL CYTOMETRY FROM BENCH TO BEDSID

On the decay of neutral V-particles

Several new examples of the decay of neutral V-particles (1-4) have been obtained recently at Pasadena, using two new magnet cloud chambers arranged to respond to cosmic-ray penetrating showers. Nine of these are of special interest in that it is possible to draw some conclusions as to the identity of the charged secondaries in each case

Comparisons of Supergranule Characteristics During the Solar Minima of Cycles 22/23 and 23/24

Supergranulation is a component of solar convection that manifests itself on the photosphere as a cellular network of around 35 Mm across, with a turnover lifetime of 1-2 days. It is strongly linked to the structure of the magnetic field. The horizontal, divergent flows within supergranule cells carry local field lines to the cell boundaries, while the rotational properties of supergranule upflows may contribute to the restoration of the poloidal field as part of the dynamo mechanism that controls the solar cycle. The solar minimum at the transition from cycle 23 to 24 was notable for its low level of activity and its extended length. It is of interest to study whether the convective phenomena that influences the solar magnetic field during this time differed in character to periods of previous minima. This study investigates three characteristics (velocity components, sizes and lifetimes) of solar supergranulation. Comparisons of these characteristics are made between the minima of cycles 22/23 and 23/24 using MDI Doppler data from 1996 and 2008, respectively. It is found that whereas the lifetimes are equal during both epochs (around 18 h), the sizes are larger in 1996 (35.9 +/- 0.3 Mm) than in 2008 (35.0 +/- 0.3 Mm), while the dominant horizontal velocity flows are weaker (139 +/- 1 m/s in 1996; 141 +/- 1 m/s in 2008). Although numerical differences are seen, they are not conclusive proof of the most recent minimum being inherently unusual.Comment: 22 pages, 5 figures. Solar Physics, in pres

Regularity issues in the problem of fluid structure interaction

We investigate the evolution of rigid bodies in a viscous incompressible fluid. The flow is governed by the 2D Navier-Stokes equations, set in a bounded domain with Dirichlet boundary conditions. The boundaries of the solids and the domain have H\"older regularity $C^{1, \alpha}$, $0 < \alpha \le 1$. First, we show the existence and uniqueness of strong solutions up to collision. A key ingredient is a BMO bound on the velocity gradient, which substitutes to the standard $H^2$ estimate for smoother domains. Then, we study the asymptotic behaviour of one $C^{1, \alpha}$ body falling over a flat surface. We show that collision is possible in finite time if and only if $\alpha < 1/2$

Antifungal activity of lipopeptides from bacillus XT1 CECT 8661 against Botrytis cinerea

This work aims to explore the capacity of a Bacillus methylotrophicus (later heterotypic synonym of Bacillus velezensis) strain named XT1 CECT 8661 against the necrotrophic plant pathogen Botrytis cinerea and to identify the compounds responsible for its activity. Q_TOF electrospray mass spectrometry analysis allows us to detect several lipopeptides – surfactin, bacillomycin, and fengycin – in XT1 cultures. In vitro antibiosis studies demonstrated the efficiency of the lipopeptide fraction for the inhibition of fungal growth. In fact, microscopy studies (SEM/TEM) revealed, an alteration of the morphology of the phytopathogen in interaction with lipopeptides, with resistance structures appearing in the early stages of growth of the fungus. Our studies, carried out with tomatoes, grapes, and strawberries have demonstrated the efficiency of Bacillus XT1 CECT 8661 lipopeptides against B. cinerea infection and it capability to trigger the antioxidant activity in fruit. Overall, the results of this study highlight the potential of lipopeptides of this strain as an effective biological control agent against the colonisation of B. cinerea.This study was supported by the European Project for Industrial Doctorates “H2020” (UGR-Ref. 4726), by the Ramón y Cajal Project (RYC-2014-15532) from MINECO and the Project Retos- Colaboración from MINECO (2015, RTC-2015-4121-2)

Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes

ABCB6, a member of the adenosine triphosphate–binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting that only three ABC transporters should be classified as mitochondrial proteins. Taken together, our results challenge the current paradigm linking the expression and function of ABCB6 to mitochondria

The importance of imprinting in the human placenta.

As a field of study, genomic imprinting has grown rapidly in the last 20 years, with a growing figure of around 100 imprinted genes known in the mouse and approximately 50 in the human. The imprinted expression of genes may be transient and highly tissue-specific, and there are potentially hundreds of other, as yet undiscovered, imprinted transcripts. The placenta is notable amongst mammalian organs for its high and prolific expression of imprinted genes. This review discusses the development of the human placenta and focuses on the function of imprinting in this organ. Imprinting is potentially a mechanism to balance parental resource allocation and it plays an important role in growth. The placenta, as the interface between mother and fetus, is central to prenatal growth control. The expression of genes subject to parental allelic expression bias has, over the years, been shown to be essential for the normal development and physiology of the placenta. In this review we also discuss the significance of genes that lack conservation of imprinting between mice and humans, genes whose imprinted expression is often placental-specific. Finally, we illustrate the importance of imprinting in the postnatal human in terms of several human imprinting disorders, with consideration of the brain as a key organ for imprinted gene expression after birth

Twist1 Suppresses Senescence Programs and Thereby Accelerates and Maintains Mutant Kras-Induced Lung Tumorigenesis

KRAS mutant lung cancers are generally refractory to chemotherapy as well targeted agents. To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required. We demonstrate in both a novel transgenic mutant Kras lung cancer mouse model and in human lung tumors that the inhibition of Twist1 restores a senescence program inducing the loss of a neoplastic phenotype. The Twist1 gene encodes for a transcription factor that is essential during embryogenesis. Twist1 has been suggested to play an important role during tumor progression. However, there is no in vivo evidence that Twist1 plays a role in autochthonous tumorigenesis. Through two novel transgenic mouse models, we show that Twist1 cooperates with KrasG12D to markedly accelerate lung tumorigenesis by abrogating cellular senescence programs and promoting the progression from benign adenomas to adenocarcinomas. Moreover, the suppression of Twist1 to physiological levels is sufficient to cause Kras mutant lung tumors to undergo senescence and lose their neoplastic features. Finally, we analyzed more than 500 human tumors to demonstrate that TWIST1 is frequently overexpressed in primary human lung tumors. The suppression of TWIST1 in human lung cancer cells also induced cellular senescence. Hence, TWIST1 is a critical regulator of cellular senescence programs, and the suppression of TWIST1 in human tumors may be an effective example of pro-senescence therapy