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1.
Variations in lipid profile and incidence of vascular events were evaluated. Group 1 had a 29.3% reduction of total and a 38.3% reduction of LDL cholesterol as against reductions of 9% and 9.6% respectively in group 2. No significant difference was observed between the two groups as far as the vascular events considered were concerned. Pravastatin is an effective and safe drug. The lack of influence on the evolution of vascular disease would appear to be correlated to the small number of subjects studied and the short follow-up. 相似文献
2.
Kemme B. Pedone F. Alonso G. Schiper A. Wiesmann M. 《Knowledge and Data Engineering, IEEE Transactions on》2003,15(4):1018-1032
Atomic broadcast primitives are often proposed as a mechanism to allow fault-tolerant cooperation between sites in a distributed system. Unfortunately, the delay incurred before a message can be delivered makes it difficult to implement high performance, scalable applications on top of atomic broadcast primitives. Recently, a new approach has been proposed for atomic broadcast which, based on optimistic assumptions about the communication system, reduces the average delay for message delivery to the application. We develop this idea further and show how applications can take even more advantage of the optimistic assumption by overlapping the coordination phase of the atomic broadcast algorithm with the processing of delivered messages. In particular, we present a replicated database architecture that employs the new atomic broadcast primitive in such a way that communication and transaction processing are fully overlapped, providing high performance without relaxing transaction correctness. 相似文献
3.
Enrico Mario Alessandro Fassi Mariangela Garofalo Jacopo Sgrignani Michele Dei Cas Matteo Mori Gabriella Roda Andrea Cavalli Giovanni Grazioso 《International journal of molecular sciences》2022,23(9)
(1) Background: Disfunctions in autophagy machinery have been identified in various conditions, including neurodegenerative diseases, cancer, and inflammation. Among mammalian autophagy proteins, the Atg8 family member GABARAP has been shown to be greatly involved in the autophagy process of prostate cancer cells, supporting the idea that GABARAP inhibitors could be valuable tools to fight the progression of tumors. (2) Methods: In this paper, starting from the X-ray crystal structure of GABARAP in a complex with an AnkirinB-LIR domain, we identify two new peptides by applying in silico drug design techniques. The two ligands are synthesized, biophysically assayed, and biologically evaluated to ascertain their potential anticancer profile. (3) Results: Two cyclic peptides (WC8 and WC10) displayed promising biological activity, high conformational stability (due to the presence of disulfide bridges), and Kd values in the low micromolar range. The anticancer assays, performed on PC-3 cells, proved that both peptides exhibit antiproliferative effects comparable to those of peptide K1, a known GABARAP inhibitor. (4) Conclusions: WC8 and WC10 can be considered new GABARAP inhibitors to be employed as pharmacological tools or even templates for the rational design of new small molecules. 相似文献
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5.
Miriam Saponaro Isabella Giacomini Giulia Morandin Veronica Cocetta Eugenio Ragazzi Genny Orso Ilaria Carnevali Massimiliano Berretta Mariangela Mancini Francesco Pagano Monica Montopoli 《International journal of molecular sciences》2020,21(23)
Benign prostatic hyperplasia (BPH) is an age-related chronic disorder, characterized by the hyperproliferation of prostatic epithelial and stromal cells, which drives prostate enlargement. Since BPH aetiology and progression have been associated with the persistence of an inflammatory stimulus, induced both by Nuclear Factor-kappa B (NF-κB) activation and reactive oxygen species (ROS) production, the inhibition of these pathways could result in a good tool for its clinical treatment. This study aimed to evaluate the antioxidant and anti-inflammatory activity of a combined formulation of Serenoa repens and Urtica dioica (SR/UD) in an in vitro human model of BPH. The results confirmed both the antioxidant and the anti-inflammatory effects of SR/UD. In fact, SR/UD simultaneously reduced ROS production, NF-κB translocation inside the nucleus, and, consequently, interleukin 6 (IL-6) and interleukin 8 (IL-8) production. Furthermore, the effect of SR/UD was also tested in a human androgen-independent prostate cell model, PC3. SR/UD did not show any significant antioxidant and anti-inflammatory effect, but was able to reduce NF-κB translocation. Taken together, these results suggested a promising role of SR/UD in BPH and BPH-linked disorder prevention. 相似文献
6.
11C‐ and 18F‐Labeled Radioligands for P‐Glycoprotein Imaging by Positron Emission Tomography 下载免费PDF全文
Dr. Mariangela Cantore Marcel Benadiba Philip H. Elsinga Chantal Kwizera Rudi A. J. O. Dierckx Nicola Antonio Colabufo Gert Luurtsema 《ChemMedChem》2016,11(1):108-118
P‐Glycoprotein (P‐gp) is an efflux transporter widely expressed at the human blood–brain barrier. It is involved in xenobiotics efflux and in onset and progression of neurodegenerative disorders. For these reasons, there is great interest in the assessment of P‐gp expression and function by noninvasive techniques such as positron emission tomography (PET). Three radiolabeled aryloxazole derivatives: 2‐[2‐(2‐methyl‐(11C)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline ([11C]‐ 5 ); 2‐[2‐(2‐fluoromethyl‐(18F)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetra‐hydroisoquinoline ([18F]‐ 6 ); and 2‐[2‐(2‐fluoroethyl‐(18F)‐5‐methoxyphenyl)oxazol‐4‐ylmethyl]‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline ([18F]‐ 7 ), were tested in several in vitro biological assays to assess the effect of the aryl substituent in terms of potency and mechanism of action toward P‐gp. Methyl derivative [11C]‐ 5 is a potent P‐gp substrate, whereas the corresponding fluoroethyl derivative [18F]‐ 7 is a P‐gp inhibitor. Fluoromethyl compound [18F]‐ 6 is classified as a non‐transported P‐gp substrate, because its efflux increases after cyclosporine A modulation. These studies revealed a promising substrate and inhibitor, [11C]‐ 5 and [18F]‐ 7 , respectively, for in vivo imaging of P‐gp by using PET. 相似文献
7.
Mariagrazia Fortino Alessandro Berselli Nicholas Stone-Weiss Lu Deng Ashutosh Goel Jincheng Du Alfonso Pedone 《Journal of the American Ceramic Society》2019,102(12):7225-7243
Borates and borosilicates are potential candidates for the design and development of glass formulations with important industrial and technological applications. A major challenge that retards the pace of development of borate/borosilicate based glasses using predictive modeling is the lack of reliable computational models to predict the structure-property relationships in these glasses over a wide compositional space. A major hindrance in this pursuit has been the complexity of boron-oxygen bonding due to which it has been difficult to develop adequate B–O interatomic potentials. In this article, we have evaluated the performance of three B–O interatomic potential models recently developed by Bauchy et al [J. Non-Cryst. Solids, 2018, 498, 294–304], Du et al [J. Am. Ceram. Soc. https://doi.org/10.1111/jace.16082 ] and Edèn et al [Phys. Chem. Chem. Phys., 2018, 20, 8192–8209] aiming to reproduce the short-to-medium range structures of sodium borosilicate glasses in the system 25 Na2O x B2O3 (75 − x) SiO2 (x = 0-75 mol%). To evaluate the different force fields, we have computed at the density functional theory level the NMR parameters of 11B, 23Na, and 29Si of the models generated with the three potentials and the simulated MAS NMR spectra compared with the experimental counterparts. It was observed that the rigid ionic models proposed by Bauchy and Du can both reliably reproduce the partitioning between BO3 and BO4 species of the investigated glasses, along with the local environment around sodium in the glass structure. However, they do not accurately reproduce the second coordination sphere of silicon ions and the Si–O–T (T = Si, B) and B-O-T distribution angles in the investigated compositional space which strongly affect the NMR parameters and final spectral shape. On the other hand, the core-shell parameterization model proposed by Edén underestimates the fraction of BO4 species of the glass with composition 25Na2O 18.4B2O3 56.6SiO2 but can accurately reproduce the shape of the 11B and 29Si MAS-NMR spectra of the glasses investigations due to the narrower B–O–T and Si-O-T bond angle distributions. Finally, the effect of the number of boron atoms (also distinguishing the BO3 and BO4 units) in the second coordination sphere of the network former cations on the NMR parameters have been evaluated. 相似文献
8.
Adele H. Marshall Mariangela Zenga 《International Transactions in Operational Research》2009,16(2):213-226
Coxian phase-type distributions are a special type of Markov model that can be used to represent survival times in terms of phases through which an individual may progress until they eventually leave the system completely. Previous research has considered the Coxian phase-type distribution to be ideal in representing patient survival in hospital. However, problems exist in fitting the distributions. This paper investigates the problems that arise with the fitting process by simulating various Coxian phase-type models for the representation of patient survival and examining the estimated parameter values and eigenvalues obtained. The results indicate that numerical methods previously used for fitting the model parameters do not always converge. An alternative technique is therefore considered. All methods are influenced by the choice of initial parameter values. The investigation uses a data set of 1439 elderly patients and models their survival time, the length of time they spend in a UK hospital. 相似文献
9.
Marcella Mastromatteo Alessandra Danza Mariangela Guida Matteo Alessandro Del Nobile 《International Journal of Food Science & Technology》2012,47(10):2109-2116
In this work, the hydration process of durum wheat–based functional bread loaded with yellow pepper flour was optimised. In particular, the investigated vegetable flour and durum wheat semolina were mixed after they were separately hydrated. Three different amounts of water added to the yellow pepper flour were studied for assessing the effect of vegetable flour hydration level on the dough development and overall quality of bread. The bread formulation investigated in a previous work, based on 25% of yellow pepper and 2% of guar seed as structuring agent where the vegetable flour was directly added to the hydrated durum wheat semolina dough, was chosen as control sample. Results highlighted that dough samples with yellow pepper flour hydrated at highest water content showed a rheological behaviour similar to the durum wheat dough. Moreover, creep analysis showed that the sample added with no‐hydrated yellow pepper flour recorded the greatest resistance to deformation. Same results were obtained for the dough tensile and bread compression tests. The use of the hydrated yellow pepper flour also improved all sensorial attributes. 相似文献
10.
Lattice dynamical calculations on trans-planar polyethylene chains containing conformational defects of the type GGTGG have been carried out. The purpose of the work is to predict the points in the vibrational infra-red and/or Raman spectrum at which a tight, (200) type, fold should show absorptions and/or scattering. Calculations are verified for the cyclic hydrocarbon C34H68 which contains two GGTGG defects. The usefulness and limitations of the vibrational spectrum as evidence for the existence of (200) tight folds are discussed. Two infra-red bands near 1342 cm?1 and a third near 700 cm?1 may indicate GGTGG defects in single crystals. Raman spectra seem insensitive to such defects. 相似文献