Sapienza University of Rome

About: Sapienza University of Rome is a education organization based out in Rome, Lazio, Italy. It is known for research contribution in the topics: Population & Large Hadron Collider. The organization has 62002 authors who have published 155468 publications receiving 4397244 citations. The organization is also known as: La Sapienza & Università La Sapienza di Roma.

Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Inhibitors: Rationale and Importance to Inhibiting These Pathways in Human Health

Abstract: William H. Chappell 1 , Linda S. Steelman 1,2 , Jacquelyn M. Long 2 , Ruth C. Kempf 2 , Stephen L. Abrams 1 , Richard A. Franklin 1 , Jorg Basecke 3 , Franca Stivala 4 , Marco Donia 4 , Paolo Fagone 4 , Graziella Malaponte 4 , Maria C. Mazzarino 4 , Ferdinando Nicoletti 4 , Massimo Libra 4 , Danijela Maksimovic-Ivanic 5 , Sanja Mijatovic 5 , Giuseppe Montalto 6 , Melchiorre Cervello 7 , Piotr Laidler 8 , Michele Milella 9 , Agostino Tafuri 10 , Antonio Bonati 11 , Camilla Evangelisti 12 , Lucio Cocco 12 , Alberto M. Martelli 12,13 , and James A. McCubrey 1 1 Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University 2 Department of Physics, Greenville, NC 27858 USA 3 Department of Medicine University of Gottingen, Gottingen, Germany 4 Department of Biomedical Sciences, University of Catania, Catania, Italy 5 Department of Immunology, Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Belgrade, Serbia 6 Department of Internal Medicine and Specialties, University of Palermo, Palermo, Italy 7 Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunologia Molecolare “Alberto Monroy”, Palermo, Italy 8 Department of Medical Biochemistry Jagiellonian University Medical College, Krakow, Poland 9 Regina Elena Cancer Center, Via Elio Chianesi n.53, Rome 00144, Italy 10 University of Rome, La Sapienza, Department of Hematology-Oncology, Via Benevento 6, Rome 99161, Italy 11 University Hospital of Parma, Unit of Hematology and Bone-Marrow Transplantation, Via Gramsi n.14, Parma 43100, Italy 12 Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell’Apparato Locomotore, Universita di Bologna, Bologna, Italy 13 IGM-CNR, Sezione di Bologna, C/o IOR, Bologna, Italy Keywords: Targeted Therapy, Combination Therapy, Drug Resistance, Cancer Stem Cells, Aging, Senescence, Raf, Akt, PI3K, mTOR Received: February 25, 2011; Accepted: March 10, 2011; Published: March 11, 2011; Correspondence: James A. McCubrey, e-mail: // // Abstract The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging.

Planck 2013 results. XXIX. The Planck catalogue of Sunyaev-Zeldovich sources

Abstract: We describe the all-sky Planck catalogue of clusters and cluster candidates derived from Sunyaev-Zeldovich (SZ) effect detections using the first 15.5 months of Planck satellite observations. The catalogue contains 1227 entries, making it over six times the size of the Planck Early SZ (ESZ) sample and the largest SZ-selected catalogue to date. It contains 861 confirmed clusters, of which 178 have been confirmed as clusters, mostly through follow-up observations, and a further 683 are previously-known clusters. The remaining 366 have the status of cluster candidates, and we divide them into three classes according to the quality of evidence that they are likely to be true clusters. The Planck SZ catalogue is the deepest all-sky cluster catalogue, with redshifts up to about one, and spans the broadest cluster mass range from (0.1 to 1.6) x 10(15) M-circle dot. Confirmation of cluster candidates through comparison with existing surveys or cluster catalogues is extensively described, as is the statistical characterization of the catalogue in terms of completeness and statistical reliability. The outputs of the validation process are provided as additional information. This gives, in particular, an ensemble of 813 cluster redshifts, and for all these Planck clusters we also include a mass estimated from a newly-proposed SZ-mass proxy. A refined measure of the SZ Compton parameter for the clusters with X-ray counter-parts is provided, as is an X-ray flux for all the Planck clusters not previously detected in X-ray surveys.

Platelet activation in obese women: role of inflammation and oxidant stress.

Abstract: ContextObesity, in particular abdominal adiposity, is associated with increased cardiovascular morbidity and mortality through mechanisms possibly linking the metabolic disorder to platelet and vascular abnormalities.ObjectiveTo investigate the clinical and biochemical determinants of lipid peroxidation and platelet activation in obese women.Design, Setting, and ParticipantsCross-sectional comparison, conducted between September 1999 and September 2001, of urinary 8-iso prostaglandin F2α (8-iso PGF2α) and 11-dehydrothromboxane B2 (11-dehyhdro-TxB2) excretion levels in 93 women: 44 with a body mass index (BMI) higher than 28 and a waist-to-hip ratio (WHR) of 0.86 or higher, android obesity; 25 with a BMI higher than 28 and a WHR lower than 0.86, gynoid obesity; and 24 nonobese women with a BMI lower than 25. An additional study was conducted to determine the short-term effects of weight loss in 20 of the 44 women with android obesity.InterventionDuring a 12-week period, 20 women with android obesity followed a weight loss program to reduce caloric intake to about 1200 kcal/d.Main Outcome MeasuresPlasma C-reactive protein, insulin and leptin levels, and urinary 8-iso PGF2α (marker of in vivo lipid peroxidation) and 11-dehyhdro-TxB2 (marker of in vivo platelet activation) excretion. Weight loss was defined as successful when the initial body weight decreased by at least 5 kg after a 12-week period of caloric restriction.ResultsWomen with android obesity had higher levels of 8-iso PGF2α (median [interquartile range {IQR}] 523 [393-685] vs 187 [140-225] pg/mg creatinine) and 11-dehyhdro-TxB2 (median [IQR], 948 [729-1296] vs 215 [184-253] pg/mg creatinine) than nonobese women (P<.001). Both 8-iso PGF2αand 11-dehyhdro-TxB2 were higher in women with android obesity than women with gynoid obesity (P<.001). Based on multiple regression analysis, C-reactive protein levels and WHRs of 0.86 or higher predicted the rate of 8-iso PGF2α excretion independently of insulin and leptin levels. Of 20 women with android obesity, 11 achieved successful weight loss, which was associated with statistically significant reductions in C-reactive protein (median change, 23%; P<.05), 8-iso PGF2α (median change, 32%; P = .04) and 11-dehydro-TxB2 (median change, 54%; P = .005).ConclusionsAndroid obesity is associated with enhanced lipid peroxidation and persistent platelet activation. These abnormalities are driven by inflammatory triggers related to the degree of abdominal adiposity and are, at least in part, reversible with a successful weight-loss program.

Collision detection and reaction: A contribution to safe physical Human-Robot Interaction

Abstract: In the framework of physical human-robot interaction (pHRI), methodologies and experimental tests are presented for the problem of detecting and reacting to collisions between a robot manipulator and a human being. Using a lightweight robot that was especially designed for interactive and cooperative tasks, we show how reactive control strategies can significantly contribute to ensuring safety to the human during physical interaction. Several collision tests were carried out, illustrating the feasibility and effectiveness of the proposed approach. While a subjective ldquosafetyrdquo feeling is experienced by users when being able to naturally stop the robot in autonomous motion, a quantitative analysis of different reaction strategies was lacking. In order to compare these strategies on an objective basis, a mechanical verification platform has been built. The proposed collision detection and reactions methods prove to work very reliably and are effective in reducing contact forces far below any level which is dangerous to humans. Evaluations of impacts between robot and human arm or chest up to a maximum robot velocity of 2.7 m/s are presented.

Making arm movements within different parts of space: dynamic aspects in the primate motor cortex

Abstract: The activity of 176 individual cells in the arm area of motor cortex (areas 4 and 6) was studied while monkeys made arm movements of similar direction within different parts of extrapersonal space The behavioral paradigm used was a 3-dimensional reaction-time task aimed at dissociating the direction of movement, which remained similar across the work space, from the patterns of muscular activity and the angular joint excursions necessary to perform these movements In agreement with other studies (Georgopoulos et al, 1982; Schwartz et al, 1988), we found that, within a given part of space, the activity of 169 (960%) cells studied increased most for a given preferred direction and less for other directions of movement This change was graded in an orderly fashion We further analyzed the orientation in space of the cells' preferred directions under the differing conditions of the task We found that, as movements with similar trajectories were made within different parts of space, the cells' preferred directions changed spatial orientation This change was of different magnitudes for different cells, but at the level of the population, it followed closely the changes in orientation of the arm necessary to perform the movements required by the task Movement population vectors (Georgopoulos et al, 1983, 1986, 1988) computed from cell activity proved to be good predictors of movement direction regardless of where in space the movements were performed These results indicate that motor cortical cells can code direction of movement in a way which is dependent on the position of the arm in space The data are discussed in relation to the existence of mechanisms which facilitate the transformation between extrinsic and intrinsic coordinates These transformations are necessary to perform arm movements to visual targets in space