A reduced-order model of three-dimensional unsteady flow in a cavity based on the resolvent operator

A novel reduced-order model for nonlinear flows is presented. The model arises from a resolvent decomposition in which the nonlinear advection terms of the Navier-Stokes equation are considered as the input to a linear system in Fourier space. Results show that Taylor-G\"ortler-like vortices can be represented from a low-order resolvent decomposition of a nonlinear lid-driven cavity flow. The present approach provides an approximation of the fluctuating velocity given the time-mean and the time history of a single velocity probe

Steady streamwise transpiration control in turbulent pipe flow

A study of the the main features of low- and high amplitude steady streamwise wall transpiration applied to pipe flow is presented. The effect of the two transpiration parameters, amplitude and wavenumber, on the flow have been investigated by means of direct numerical simulation at a moderate turbulent Reynolds number. The behaviour of the three identified mechanisms that act in the flow: modification of Reynolds shear stress, steady streaming and generation of non-zero mean streamwise gradients, have been linked to the transpiration parameters. The observed trends have permitted the identification of wall transpiration configurations able to reduce or increase the overall flow rate in -36.1% and 19.3% respectively. A resolvent analysis has been carried out to obtain a description of the reorganization of the flow structures induced by the transpiration

Sustainability through Agroforestry in Himalayas: An overview

This record was migrated from the OpenDepot repository service in June, 2017 before shutting down

The Usefulness of the APACHE II Score in Obstetric Critical Care: A Structured Review.

OBJECTIVE: To assess the performance of the Acute Physiology and Chronic Health Evaluation II (APACHE II) mortality prediction model in pregnant and recently pregnant women receiving critical care in low-, middle-, and high-income countries during the study period (1985-2015), using a structured literature review. DATA SOURCES: Ovid MEDLINE, Embase, Web of Science, and Evidence-Based Medicine Reviews, searched for articles published between 1985 and 2015. STUDY SELECTION: Twenty-five studies (24 publications), of which two were prospective, were included in the analyses. Ten studies were from high-income countries (HICs), and 15 were from low- and middle-income countries (LMICs). Median study duration and size were six years and 124 women, respectively. DATA SYNTHESIS: ICU admission complicates 0.48% of deliveries, and pregnant and recently pregnant women account for 1.49% of ICU admissions. One quarter were admitted while pregnant, three quarters of these for an obstetric indication and for a median of three days. The median APACHE II score was 10.9, with a median APACHE II-predicted mortality of 16.6%. Observed mortality was 4.6%, and the median standardized mortality ratio was 0.36 (interquartile range 0.23 to 0.73). The standardized mortality ratio was < 0.9 in 24 of 25 studies. Women in HICs were more frequently admitted with a medical comorbidity but were less likely to die than were women in LMICs. CONCLUSION: The APACHE II score consistently overestimates mortality risks for pregnant and recently pregnant women receiving critical care, whether they reside in HICs or LMICs. There is a need for a pregnancy-specific outcome prediction model for these women

Vangl2-Regulated Polarisation of Second Heart Field-Derived Cells Is Required for Outflow Tract Lengthening during Cardiac Development.

Planar cell polarity (PCP) is the mechanism by which cells orient themselves in the plane of an epithelium or during directed cell migration, and is regulated by a highly conserved signalling pathway. Mutations in the PCP gene Vangl2, as well as in other key components of the pathway, cause a spectrum of cardiac outflow tract defects. However, it is unclear why cells within the mesodermal heart tissue require PCP signalling. Using a new conditionally floxed allele we show that Vangl2 is required solely within the second heart field (SHF) to direct normal outflow tract lengthening, a process that is required for septation and normal alignment of the aorta and pulmonary trunk with the ventricular chambers. Analysis of a range of markers of polarised epithelial tissues showed that in the normal heart, undifferentiated SHF cells move from the dorsal pericardial wall into the distal outflow tract where they acquire an epithelial phenotype, before moving proximally where they differentiate into cardiomyocytes. Thus there is a transition zone in the distal outflow tract where SHF cells become more polarised, turn off progenitor markers and start to differentiate to cardiomyocytes. Membrane-bound Vangl2 marks the proximal extent of this transition zone and in the absence of Vangl2, the SHF-derived cells are abnormally polarised and disorganised. The consequent thickening, rather than lengthening, of the outflow wall leads to a shortened outflow tract. Premature down regulation of the SHF-progenitor marker Isl1 in the mutants, and accompanied premature differentiation to cardiomyocytes, suggests that the organisation of the cells within the transition zone is important for maintaining the undifferentiated phenotype. Thus, Vangl2-regulated polarisation and subsequent acquisition of an epithelial phenotype is essential to lengthen the tubular outflow vessel, a process that is essential for on-going cardiac morphogenesis

MAK-4 and -5 supplemented diet inhibits liver carcinogenesis in mice

<p>Abstract</p> <p>Background</p> <p>Maharishi Amrit Kalash (MAK) is an herbal formulation composed of two herbal mixtures, MAK-4 and MAK-5. These preparations are part of a natural health care system from India, known as Maharishi Ayur-Veda. MAK-4 and MAK-5 are each composed of different herbs and are said to have maximum benefit when used in combination. This investigation evaluated the cancer inhibiting effects of MAK-4 and MAK-5, <it>in vitro </it>and <it>in vivo</it>.</p> <p>Methods</p> <p><it>In vitro </it>assays: Aqueous extracts of MAK-4 and MAK-5 were tested for effects on <it>ras </it>induced cell transformation in the Rat 6 cell line assessed by focus formation assay. <it>In vivo </it>assays: Urethane-treated mice were put on a standard pellet diet or a diet supplemented with MAK-4, MAK-5 or both. At 36 weeks, livers were examined for tumors, sera for oxygen radical absorbance capacity (ORAC), and liver homogenates for enzyme activities of glutathione peroxidase (GPX), glutathione-S-transferase (GST), and NAD(P)H: quinone reductase (QR). Liver fragments of MAK-fed mice were analyzed for connexin (cx) protein expression.</p> <p>Results</p> <p>MAK-5 and a combination of MAK-5 plus MAK-4, inhibited <it>ras</it>-induced cell transformation. In MAK-4, MAK-5 and MAK4+5-treated mice we observed a 35%, 27% and 46% reduction in the development of urethane-induced liver nodules respectively. MAK-4 and MAK4+5-treated mice had a significantly higher ORAC value (<it>P </it>< 0.05) compared to controls (200.2 ± 33.7 and 191.6 ± 32.2 <it>vs. </it>152.2 ± 15.7 ORAC units, respectively). The urethane-treated MAK-4, MAK-5 and MAK4+5-fed mice had significantly higher activities of liver cytosolic enzymes compared to the urethane-treated controls and to untreated mice: GPX(0.23 ± 0.08, 0.21 ± 0.05, 0.25 ± 0.04, 0.20 ± 0.05, 0.21 ± 0.03 U/mg protein, respectively), GST (2.0 ± 0.4, 2.0 ± 0.6, 2.1 ± 0.3, 1.7 ± 0.2, 1.7 ± 0.2 U/mg protein, respectively) and QR (0.13 ± 0.02, 0.12 ± 0.06, 0.15 ± 0.03, 0.1 ± 0.04, 0.11 ± 0.03 U/mg protein, respectively). Livers of MAK-treated mice showed a time-dependent increased expression of cx32.</p> <p>Conclusion</p> <p>Our results show that a MAK-supplemented diet inhibits liver carcinogenesis in urethane-treated mice. The prevention of excessive oxidative damage and the up-regulation of connexin expression are two of the possible effects of these products.</p

Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells

Chronic myeloid leukaemia (CML) is maintained by a rare population of tyrosine kinase inhibitor (TKI)-insensitive malignant stem cells. Our long-term aim is to find a BcrAbl-independent drug that can be combined with a TKI to improve overall disease response in chronic-phase CML. Omacetaxine mepesuccinate, a first in class cetaxine, has been evaluated by clinical trials in TKI-insensitive/resistant CML. Omacetaxine inhibits synthesis of anti-apoptotic proteins of the Bcl-2 family, including (myeloid cell leukaemia) Mcl-1, leading to cell death. Omacetaxine effectively induced apoptosis in primary CML stem cells (CD34&lt;sup&gt;+&lt;/sup&gt;38&lt;sup&gt;lo&lt;/sup&gt;) by downregulation of Mcl-1 protein. In contrast to our previous findings with TKIs, omacetaxine did not accumulate undivided cells &lt;i&gt;in vitro&lt;/i&gt;. Furthermore, the functionality of surviving stem cells following omacetaxine exposure was significantly reduced in a dose-dependant manner, as determined by colony forming cell and the more stringent long-term culture initiating cell colony assays. This stem cell-directed activity was not limited to CML stem cells as both normal and non-CML CD34&lt;sup&gt;+&lt;/sup&gt; cells were sensitive to inhibition. Thus, although omacetaxine is not leukaemia stem cell specific, its ability to induce apoptosis of leukaemic stem cells distinguishes it from TKIs and creates the potential for a curative strategy for persistent disease

Small molecule inhibitor of Igf2bp1 represses Kras and a pro-oncogenic phenotype in cancer cells

Igf2bp1 is an oncofetal RNA binding protein whose expression in numerous types of cancers is associated with upregulation of key pro-oncogenic RNAs, poor prognosis, and reduced survival. Importantly, Igf2bp1 synergizes with mutations in Kras to enhance signalling and oncogenic activity, suggesting that molecules inhibiting Igf2bp1 could have therapeutic potential. Here, we isolate a small molecule that interacts with a hydrophobic surface at the boundary of Igf2bp1 KH3 and KH4 domains, and inhibits binding to Kras RNA. In cells, the compound reduces the level of Kras and other Igf2bp1 mRNA targets, lowers Kras protein, and inhibits downstream signalling, wound healing, and growth in soft agar, all in the absence of any toxicity. This work presents an avenue for improving the prognosis of Igf2bp1-expressing tumours in lung, and potentially other, cancer(s)

Indexes to Find the Optimal Number of Clusters in a Hierarchical Clustering

Clustering analysis is one of the most commonly used techniques for uncovering patterns in data mining. Most clustering methods require establishing the number of clusters beforehand. However, due to the size of the data currently used, predicting that value is at a high computational cost task in most cases. In this article, we present a clustering technique that avoids this requirement, using hierarchical clustering. There are many examples of this procedure in the literature, most of them focusing on the dissociative or descending subtype, while in this article we cover the agglomerative or ascending subtype. Being more expensive in computational and temporal cost, it nevertheless allows us to obtain very valuable information, regarding elements membership to clusters and their groupings, that is to say, their dendrogram. Finally, several sets of data have been used, varying their dimensionality. For each of them, we provide the calculations of internal validation indexes to test the algorithm developed, studying which of them provides better results to obtain the best possible clustering

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al