A general trimming approach to robust Cluster Analysis

We introduce a new method for performing clustering with the aim of fitting clusters with different scatters and weights. It is designed by allowing to handle a proportion $\alpha$ of contaminating data to guarantee the robustness of the method. As a characteristic feature, restrictions on the ratio between the maximum and the minimum eigenvalues of the groups scatter matrices are introduced. This makes the problem to be well defined and guarantees the consistency of the sample solutions to the population ones. The method covers a wide range of clustering approaches depending on the strength of the chosen restrictions. Our proposal includes an algorithm for approximately solving the sample problem.Comment: Published in at http://dx.doi.org/10.1214/07-AOS515 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Morphometrics and compositional classes. The stuy of anthropomorphic sculptures from Teotihuacan (México)

Morphometry is defined as the measurement of the external and perceptible characteristics, i.e., in a first approximation, of the shape or morphology of an object. It includes information related to the object’s appearance as well as to its physical and diachronic constitution (Verrecchia, 2003). Morphometric studies attempt to describe this form or shape through mathematical relationships that allow numerical data, and this can be achieved in different ways. In general, tow main types of analysis can be performed whether they are or they are not based on the study of the contourn. In several instances, the actual contourn is not supposed to be really informative. Instead, elementary Euclidean geometrical measurements or the definition of significant points (landmarks or semi-landmarks), referenced in coordinates systems, are used

The District Energy-Efficient Retrofitting of Torrelago (Laguna de Duero – Spain)

The urban growth is estimated to reach up the 66 % by 2050 and consequently the need of resources within the cities will increase significantly. This, combined with the 40 % of energy consumption and 36 % of CO2 emissions of the building sector, makes necessary to accelerate the transition towards more sustainable cities. The CITyFiED project contributes to this transition, aiming to develop an innovative and holistic methodological approach for energy-efficient district renovation and deliver three large scale demonstration cases in the cities of Lund (Sweden), Laguna de Duero (Spain) and Soma (Turkey). CITyFiED methodology consists of several phases that ease the decision-making tasks towards the district renovation, considering the energy efficiency as the main pillar and local authorities as clients. For the case of Torrelago district (Spain) the intervention consists of a set of energy conservative measures including the facąde retrofitting of 143.025 m2 of living space in 31 twelve-storey buildings; the renovation of the district heating network with a new biomass thermal plant; the integration of renewable energy sources, including a micro-cogeneration system, and the installation of individual smart meters. After the renovation action, one-year monitoring campaign is ongoing. The CITyFiED monitoring platform will collect information from the energy systems and deliver environmental, technical, economic and social key performance indicators by March 2019. At the end of the project the achievement of the predefined goals will be verified: Up to 36 % of energy saving and 3,429 tons-CO2/yr emissions saving covering the 59,4 % of the energy consumption with renewable sources.The research and results presented in this paper evolve from activities related to the CITyFiED project, which has received funding from the European Commission under the Grant Agreement no. 609129. This article is the result of cooperative research work of many experts from various countries and we would like to gratefully acknowledge the rest of the CITyFiED partners

Reduction of motion effects in myocardial arterial spin labeling

Purpose To evaluate the accuracy and reproducibility of myocardial blood flow measurements obtained under different breathing strategies and motion correction techniques with arterial spin labeling. Methods A prospective cardiac arterial spin labeling study was performed in 12 volunteers at 3 Tesla. Perfusion images were acquired twice under breath-hold, synchronized-breathing, and free-breathing. Motion detection based on the temporal intensity variation of a myocardial voxel, as well as image registration based on pairwise and groupwise approaches, were applied and evaluated in synthetic and in vivo data. A region of interest was drawn over the mean perfusion-weighted image for quantification. Original breath-hold datasets, analyzed with individual regions of interest for each perfusion-weighted image, were considered as reference values. Results Perfusion measurements in the reference breath-hold datasets were in line with those reported in literature. In original datasets, prior to motion correction, myocardial blood flow quantification was significantly overestimated due to contamination of the myocardial perfusion with the high intensity signal of blood pool. These effects were minimized with motion detection or registration. Synthetic data showed that accuracy of the perfusion measurements was higher with the use of registration, in particular after the pairwise approach, which probed to be more robust to motion. Conclusion Satisfactory results were obtained for the free-breathing strategy after pairwise registration, with higher accuracy and robustness (in synthetic datasets) and higher intrasession reproducibility together with lower myocardial blood flow variability across subjects (in in vivo datasets). Breath-hold and synchronized-breathing after motion correction provided similar results, but these breathing strategies can be difficult to perform by patients

Cilastatin Attenuates Cisplatin-Induced Proximal Tubular Cell Damage

A major area in cancer therapy is the search for protective strategies against cisplatin-induced nephrotoxicity. We investigated the protective effect of cilastatin on cisplatininduced injury to renal proximal tubular cells. Cilastatin is a specific inhibitor of renal dehydrodipeptidase I (DHP-I), which prevents hydrolysis of imipenem and its accumulation in the proximal tubule. Primary cultures of proximal cells were treated with cisplatin (1–30 M) in the presence or absence of cilastatin (200 g/ml). Apoptosis and mitochondrial injury were assessed by different techniques. Cisplatin uptake and DNA binding were measured by inductively coupled plasma spectrometry. HeLa cells were used to control the effect of cilastatin on the tumoricidal activity of cisplatin. Cisplatin increased cell death, apoptotic-like morphology, caspase activation, and mitochondrial injury in proximal tubular cells in a dose- and time-dependent way. Concomitant treatment with cilastatin reduced cisplatin-induced changes. Cilastatin also reduced the DNA-bound platinum but did not modify cisplatin-dependent up-regulation of death receptors (Fas) or ligands (tumor necrosis factor , Fas ligand). In contrast, cilastatin did not show any effects on cisplatintreated HeLa cells. Renal DHP-I was virtually absent in HeLa cells. Cilastatin attenuates cisplatin-induced cell death in proximal tubular cells without reducing the cytotoxic activity of cisplatin in tumor cells. Our findings suggest that the affinity of cilastatin for renal dipeptidase makes this effect specific for proximal tubular cells and may be related to a reduction in intracellular drug accumulation. Therefore, cilastatin administration might represent a novel strategy in the prevention of cisplatin-induced acute renal injury

Regulation of Apoptotic Effects by Erythrocarpine E, a Cytotoxic Limonoid from Chisocheton erythrocarpus in HSC-4 Human Oral Cancer Cells

The aim of this study was to determine the cytotoxic and apoptotic effects of erythrocarpine E (CEB4), a limonoid extracted from Chisocheton erythrocarpus on human oral squamous cell carcinoma. Based on preliminary dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays, CEB4 treated HSC-4 cells demonstrated a cytotoxic effect and inhibited cell proliferation in a time and dose dependent manner with an IC50 value of 4.0±1.9 µM within 24 h of treatment. CEB4 was also found to have minimal cytotoxic effects on the normal cell line, NHBE with cell viability levels maintained above 80% upon treatment. Annexin V-fluorescein isothiocyanate (FITC), poly-ADP ribose polymerase (PARP) cleavage and DNA fragmentation assay results showed that CEB4 induces apoptosis mediated cell death. Western blotting results demonstrated that the induction of apoptosis by CEB4 appeared to be mediated through regulation of the p53 signalling pathway as there was an increase in p53 phosphorylation levels. CEB4 was also found to up-regulate the pro-apoptotic protein, Bax, while down-regulating the anti-apoptotic protein, Bcl-2, suggesting the involvement of the intrinsic mitochondrial pathway. Reduced levels of initiator procaspase-9 and executioner caspase-3 zymogen were also observed following CEB4 exposure, hence indicating the involvement of cytochrome c mediated apoptosis. These results demonstrate the cytotoxic and apoptotic ability of erythrocarpine E, and suggest its potential development as a cancer chemopreventive agent

Efficient Induction of Extrinsic Cell Death by Dandelion Root Extract in Human Chronic Myelomonocytic Leukemia (CMML) Cells

BACKGROUND: Chronic Myelomonocytic Leukemia (CMML) is a heterogeneous disease that is not only hard to diagnose and classify, but is also highly resistant to treatment. Available forms of therapy for this disease have not shown significant effects and patients rapidly develop resistance early on in therapy. These factors lead to the very poor prognosis observed with CMML patients, with median survival duration between 12 and 24 months after diagnosis. This study is therefore centered around evaluating the selective efficacy of a natural extract from dandelion roots, in inducing programmed cell death in aggressive and resistant CMML cell lines. METHODOLOGY/PRINCIPAL FINDINGS: To confirm the induction of programmed cell death in three human CMML cell lines, nuclear condensation and externalization of the phosphatidylserine, two main characteristics of apoptosis, were detected using Hoechst staining and annexin-V binding assay. The induction of another mode of cell death, autophagy, was determined using a monodansylcadaverine (MDC) stain, to detect the formation of autophagy vacuoles. The results from this study indicate that Dandelion Root Extract (DRE) is able to efficiently and selectively induce apoptosis and autophagy in these cell lines in a dose and time dependent manner, with no significant toxicity on non-cancerous peripheral blood mononuclear cells. More importantly, we observed early activation of initiator caspase-8, which led to mitochondrial destabilization and the induction of autophagy, suggesting that DRE acts through the extrinsic pathway of apoptosis. The inability of DRE to induce apoptosis in dominant-negative FADD cells, confirms the mechanism of action of DRE in in vitro models of CMML. CONCLUSION: The results from this study indicate that natural products, in particular Dandelion Root Extract, have great potential, as non-toxic and effective alternatives to conventional modes of chemotherapy available today

Diet-induced dyslipidemia induces metabolic and migratory adaptations in regulatory T cells

A hallmark of advanced atherosclerosis is inadequate immunosuppression by regulatory T(Treg) cells inside atherosclerotic lesions. Dyslipidemia has been suggested to alter Treg cellmigration by affecting the expression of specific membrane proteins, thereby decreasing Treg cellmigration towards atherosclerotic lesions. Besides membrane proteins, cellular metabolism has beenshown to be a crucial factor in Treg cell migration. We aimed to determine whether dyslipidemiacontributes to altered migration of Treg cells, in part, by affecting cellular metabolism.Dyslipidemia was induced by feeding Ldlr-/- mice a Western-type diet for 16-20weeks and intrinsic changes in Treg cells affecting their migration and metabolism were examined.Dyslipidemia was associated with altered mTORC2 signaling in Treg cells, decreased expression ofmembrane proteins involved in migration, including CD62L, CCR7 and S1Pr1, and decreased Tregcell migration towards lymph nodes. Furthermore, we discovered that diet-induced dyslipidemiainhibited mTORC1 signaling, induced PPARδ activation and increased fatty acid (FA) oxidation inTreg cells. Moreover, mass-spectrometry analysis of serum from Ldlr-/- mice with normolipidemia ordyslipidemia showed increases in multiple PPARδ ligands during dyslipidemia. Treatment with asynthetic PPARδ agonist increased the migratory capacity of Treg cells in vitro and in vivo in an FAoxidation dependent manner. Furthermore, diet-induced dyslipidemia actually enhanced Treg cellmigration into the inflamed peritoneum and into atherosclerotic lesions in vitro.Altogether, our findings implicate that dyslipidemia does not contribute toatherosclerosis by impairing Treg cell migration as dyslipidemia associated with an effector-likemigratory phenotype in Treg cells.Analytical BioScience