MaxMin Linear Initialization for Fuzzy C-Means

International audienceClustering is an extensive research area in data science. The aim of clustering is to discover groups and to identify interesting patterns in datasets. Crisp (hard) clustering considers that each data point belongs to one and only one cluster. However, it is inadequate as some data points may belong to several clusters, as is the case in text categorization. Thus, we need more flexible clustering. Fuzzy clustering methods, where each data point can belong to several clusters, are an interesting alternative. Yet, seeding iterative fuzzy algorithms to achieve high quality clustering is an issue. In this paper, we propose a new linear and efficient initialization algorithm MaxMin Linear to deal with this problem. Then, we validate our theoretical results through extensive experiments on a variety of numerical real-world and artificial datasets. We also test several validity indices, including a new validity index that we propose, Transformed Standardized Fuzzy Difference (TSFD)

Observation of Quantum Interference in Molecular Charge Transport

As the dimensions of a conductor approach the nano-scale, quantum effects will begin to dominate its behavior. This entails the exciting possibility of controlling the conductance of a device by direct manipulation of the electron wave function. Such control has been most clearly demonstrated in mesoscopic semiconductor structures at low temperatures. Indeed, the Aharanov-Bohm effect, conductance quantization and universal conductance fluctuations are direct manifestations of the electron wave nature. However, an extension of this concept to more practical emperatures has not been achieved so far. As molecules are nano-scale objects with typical energy level spacings (~eV) much larger than the thermal energy at 300 K (~25 meV), they are natural candidates to enable such a break-through. Fascinating phenomena including giant magnetoresistance, Kondo effects and conductance switching, have previously been demonstrated at the molecular level. Here, we report direct evidence for destructive quantum interference in charge transport through two-terminal molecular junctions at room temperature. Furthermore, we show that the degree of interference can be controlled by simple chemical modifications of the molecule. Not only does this provide the experimental demonstration of a new phenomenon in quantum charge transport, it also opens the road for a new type of molecular devices based on chemical or electrostatic control of quantum interference

Inhibition of lipoxygenase affects induction of both direct and indirect plant defences against herbivorous insects

Herbivore-induced plant defences influence the behaviour of insects associated with the plant. For biting–chewing herbivores the octadecanoid signal-transduction pathway has been suggested to play a key role in induced plant defence. To test this hypothesis in our plant—herbivore—parasitoid tritrophic system, we used phenidone, an inhibitor of the enzyme lipoxygenase (LOX), that catalyses the initial step in the octadecanoid pathway. Phenidone treatment of Brussels sprouts plants reduced the accumulation of internal signalling compounds in the octadecanoid pathway downstream of the step catalysed by LOX, i.e. 12-oxo-phytodienoic acid (OPDA) and jasmonic acid. The attraction of Cotesia glomerata parasitoids to host-infested plants was significantly reduced by phenidone treatment. The three herbivores investigated, i.e. the specialists Plutella xylostella, Pieris brassicae and Pieris rapae, showed different oviposition preferences for intact and infested plants, and for two species their preference for either intact or infested plants was shown to be LOX dependent. Our results show that phenidone inhibits the LOX-dependent defence response of the plant and that this inhibition can influence the behaviour of members of the associated insect community

Identification of Novel Functional Inhibitors of Acid Sphingomyelinase

We describe a hitherto unknown feature for 27 small drug-like molecules, namely functional inhibition of acid sphingomyelinase (ASM). These entities named FIASMAs (Functional Inhibitors of Acid SphingoMyelinAse), therefore, can be potentially used to treat diseases associated with enhanced activity of ASM, such as Alzheimer's disease, major depression, radiation- and chemotherapy-induced apoptosis and endotoxic shock syndrome. Residual activity of ASM measured in the presence of 10 µM drug concentration shows a bimodal distribution; thus the tested drugs can be classified into two groups with lower and higher inhibitory activity. All FIASMAs share distinct physicochemical properties in showing lipophilic and weakly basic properties. Hierarchical clustering of Tanimoto coefficients revealed that FIASMAs occur among drugs of various chemical scaffolds. Moreover, FIASMAs more frequently violate Lipinski's Rule-of-Five than compounds without effect on ASM. Inhibition of ASM appears to be associated with good permeability across the blood-brain barrier. In the present investigation, we developed a novel structure-property-activity relationship by using a random forest-based binary classification learner. Virtual screening revealed that only six out of 768 (0.78%) compounds of natural products functionally inhibit ASM, whereas this inhibitory activity occurs in 135 out of 2028 (6.66%) drugs licensed for medical use in humans

Therapeutic Potential of HDL in Cardioprotection and Tissue Repair

Epidemiological studies support a strong association between high-density lipoprotein (HDL) cholesterol levels and heart failure incidence. Experimental evidence from different angles supports the view that low HDL is unlikely an innocent bystander in the development of heart failure. HDL exerts direct cardioprotective effects, which are mediated via its interactions with the myocardium and more specifically with cardiomyocytes. HDL may improve cardiac function in several ways. Firstly, HDL may protect the heart against ischaemia/reperfusion injury resulting in a reduction of infarct size and thus in myocardial salvage. Secondly, HDL can improve cardiac function in the absence of ischaemic heart disease as illustrated by beneficial effects conferred by these lipoproteins in diabetic cardiomyopathy. Thirdly, HDL may improve cardiac function by reducing infarct expansion and by attenuating ventricular remodelling post-myocardial infarction. These different mechanisms are substantiated by in vitro, ex vivo, and in vivo intervention studies that applied treatment with native HDL, treatment with reconstituted HDL, or human apo A-I gene transfer. The effect of human apo A-I gene transfer on infarct expansion and ventricular remodelling post-myocardial infarction illustrates the beneficial effects of HDL on tissue repair. The role of HDL in tissue repair is further underpinned by the potent effects of these lipoproteins on endothelial progenitor cell number, function, and incorporation, which may in particular be relevant under conditions of high endothelial cell turnover. Furthermore, topical HDL therapy enhances cutaneous wound healing in different models. In conclusion, the development of HDL-targeted interventions in these strategically chosen therapeutic areas is supported by a strong clinical rationale and significant preclinical data.status: publishe

A user's guide to the Encyclopedia of DNA elements (ENCODE)

The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone