Dealing with Distances and Transformations for Fuzzy C-Means Clustering of Compositional Data

Clustering techniques are based upon a dissimilarity or distance measure between objects and clusters. This paper focuses on the simplex space, whose elements??compositions??are subject to non-negativity and constant-sum constraints. Any data analysis involving compositions should fulfill two main principles: scale invariance and subcompositional coherence. Among fuzzy clustering methods, the FCM algorithm is broadly applied in a variety of fields, but it is not well-behaved when dealing with compositions. Here, the adequacy of different dissimilarities in the simplex, together with the behavior of the common log-ratio transformations, is discussed in the basis of compositional principles. As a result, a well-founded strategy for FCM clustering of compositions is suggested. Theoretical findings are accompanied by numerical evidence, and a detailed account of our proposal is provided. Finally, a case study is illustrated using a nutritional data set known in the clustering literature.     

Activation of ataxia telangiectasia muted under experimental models and human Parkinson’s disease

In the present study we demonstrated that neurotoxin MPP⁺-induced DNA damage is followed by ataxia telangiectasia muted (ATM) activation either in cerebellar granule cells (CGC) or in B65 cell line. In CGC, the selective ATM inhibitor KU-55933 showed neuroprotective effects against MPP⁺-induced neuronal cell loss and apoptosis, lending support to the key role of ATM in experimental models of Parkinson’s disease. Likewise, we showed that knockdown of ATM levels in neuroblastoma B65 cells using an ATM-specific siRNA attenuates the phosphorylation of retinoblastoma protein without affecting other cell-cycle proteins involved in the G₀/G₁ cell-cycle phase. Moreover, we demonstrated DNA damage, in human brain samples of PD patients. These findings support a model in which MPP⁺ leads to ATM activation with a subsequent DNA damage response and activation of pRb. Therefore, this study demonstrates a new link between DNA damage by MPP⁺ and cell-cycle re-entry through retinoblastoma protein phosphorylation.     

Book Reviews

José María Albareda (1902–1966) was an applied chemist and a prominent member of the Roman Catholic organization, Opus Dei, who played a crucial role in organizing the Consejo Superior de Investigaciones Científicas (CSIC), the new scientific institution created by the Franco regime in 1939. The paper analyses first the formative years in Albareda's scientific biography and the political and social context in which he became an Opus Dei fellow. Then it discusses the CSIC's innovative features compared with the Junta para Ampliación de Estudios (JAE), the institution in charge of scientific research and science policy in Spain from 1907 up to the Civil War (1936–1939). Next it goes into Albareda's ideas about science and science policy. Finally, it shows how they shaped the organization of the CSIC, of which Albareda was the General Secretary from 1939 to his untimely death in 1966.     

Difference in resistance of subunits A and B ofVibrio cholerae toxin (choleragen) to treatment with pronase

Summary Disc electrophoresis in sodium dodecyl sulphate, performed on choleragen after incubation with pronase, only showed the band corresponding to the B subunit, while the A subunit was lost. When examined in immunodiffusion, the digested choleragen was still able to precipitate with specific antibodies. On the other hand, toxicity was considerably reduced.     

Some observations on the effect of Ro 7-1051 on Trypanosoma cruzi,particularly in cell culture

Summary The drug Ro 7-1051 showed a deleterious effect on the intracellular and extracellular forms of Trypanosoma cruzi represented by nuclear pyknosis, fragmentation and lysis of parasites and by its reduced susceptibility to infection.Acknowledgments. The authors are deeply thankful to Roche Products for supplying the drug and for valuable information. The authors are also grateful to Prof. Nelson Villa for criticism and to Miss edna Bertin for technical assistance     

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

Drug resistance presents a challenge to the treatment of cancer patients. Many studies have focused on cell-autonomous mechanisms of drug resistance. By contrast, we proposed that the tumour micro-environment confers innate resistance to therapy. Here we developed a co-culture system to systematically assay the ability of 23 stromal cell types to influence the innate resistance of 45 cancer cell lines to 35 anticancer drugs. We found that stroma-mediated resistance is common, particularly to targeted agents. We characterized further the stroma-mediated resistance of BRAF-mutant melanoma to RAF inhibitors because most patients with this type of cancer show some degree of innate resistance. Proteomic analysis showed that stromal cell secretion of hepatocyte growth factor (HGF) resulted in activation of the HGF receptor MET, reactivation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-OH kinase (PI(3)K)-AKT signalling pathways, and immediate resistance to RAF inhibition. Immunohistochemistry experiments confirmed stromal cell expression of HGF in patients with BRAF-mutant melanoma and showed a significant correlation between HGF expression by stromal cells and innate resistance to RAF inhibitor treatment. Dual inhibition of RAF and either HGF or MET resulted in reversal of drug resistance, suggesting RAF plus HGF or MET inhibitory combination therapy as a potential therapeutic strategy for BRAF-mutant melanoma. A similar resistance mechanism was uncovered in a subset of BRAF-mutant colorectal and glioblastoma cell lines. More generally, this study indicates that the systematic dissection of interactions between tumours and their micro-environment can uncover important mechanisms underlying drug resistance.     

The design analyze of new hybrid drive concept

This paper presents the design method of hybrid drive system for the minibus with some limited conditions. The approach of design hybrid drive system is based on the dynamic modeling and simulation of the hybrid minibus with planetary gear system. The main target of the design is to obtain the optimal design with the proper hybrid drive configuration and control for a given set of design constraints. In oder to meet the design target, it's necessary to adjust some parameters such as mechanical ratios and parameters of battery pack as well as control by simulation. During simulation the transient operating process can be studied in details with the dynamic model in Matlab/Simulink. The control strategy can be optimized by running the simulation and monitoring the operation of each components: the operating area of internal combustion engine (ICE), fuel consumption (energy consumption), the power distribution, the torque and rotary speed of ICE and motor, the operating efficiency of motor, the alteration of battery state of charge (SOC), current and voltage.