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排序方式: 共有580条查询结果,搜索用时 31 毫秒
1.
Bokyung Kim Young Ho Ko Massimiliano Runfola Simona Rapposelli Gabriella Ortore Grazia Chiellini Jin Hae Kim 《International journal of molecular sciences》2021,22(7)
Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases. 相似文献
2.
Veronica Cocetta Vincenzo Quagliariello Francesco Fiorica Massimiliano Berretta Monica Montopoli 《International journal of molecular sciences》2021,22(4)
Resistance to chemotherapy still remains a major challenge in the clinic, impairing the quality of life and survival rate of patients. The identification of unconventional chemosensitizing agents is therefore an interesting aspect of cancer research. Resveratrol has emerged in the last decades as a fascinating molecule, able to modulate several cancer-related molecular mechanisms, suggesting a possible application as an adjuvant in cancer management. This review goes deep into the existing literature concerning the possible chemosensitizing effect of resveratrol associated with the most conventional chemotherapeutic drugs. Despite the promising effects observed in different cancer types in in vitro studies, the clinical translation still presents strong limitations due to the low bioavailability of resveratrol. Recently, efforts have been moved in the field of drug delivery to identifying possible strategies/formulations useful for a more effective administration. Despite the necessity of a huge implementation in this research area, resveratrol appears as a promising molecule able to sensitize resistant tumors to drugs, suggesting its potential use in therapy-refractory cancer patients. 相似文献
3.
4.
Filippo Lococo Massimiliano Paci Cristian Rapicetta Teresa Rossi Valentina Sancisi Luca Braglia Silvio Cavuto Alessandra Bisagni Italia Bongarzone Douglas M. Noonan Adriana Albini Sally Maramotti 《International journal of molecular sciences》2015,16(8):19612-19630
Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies. 相似文献
5.
Massimiliano Corsini Elisa Drelie Gelasca Touradj Ebrahimi Mauro Barni 《Multimedia, IEEE Transactions on》2007,9(2):247-256
This paper addresses the problem of assessing distortions produced by watermarking 3D meshes. In particular, a new methodology for subjective evaluation of the quality of 3D objects is proposed and implemented. Two objective metrics derived from measures of surface roughness are then proposed and their efficiency to predict the perceptual impact of 3D watermarking is assessed and compared with the state of the art. Results obtained show good correlations between the proposed objective metrics and subjective assessments by human observers 相似文献
6.
Foutse Khomh Massimiliano Di Penta Yann-Ga?l Guéhéneuc Giuliano Antoniol 《Empirical Software Engineering》2012,17(3):243-275
Antipatterns are poor design choices that are conjectured to make object-oriented systems harder to maintain. We investigate
the impact of antipatterns on classes in object-oriented systems by studying the relation between the presence of antipatterns
and the change- and fault-proneness of the classes. We detect 13 antipatterns in 54 releases of ArgoUML, Eclipse, Mylyn, and
Rhino, and analyse (1) to what extent classes participating in antipatterns have higher odds to change or to be subject to
fault-fixing than other classes, (2) to what extent these odds (if higher) are due to the sizes of the classes or to the presence
of antipatterns, and (3) what kinds of changes affect classes participating in antipatterns. We show that, in almost all releases
of the four systems, classes participating in antipatterns are more change-and fault-prone than others. We also show that
size alone cannot explain the higher odds of classes with antipatterns to underwent a (fault-fixing) change than other classes.
Finally, we show that structural changes affect more classes with antipatterns than others. We provide qualitative explanations
of the increase of change- and fault-proneness in classes participating in antipatterns using release notes and bug reports.
The obtained results justify a posteriori previous work on the specification and detection of antipatterns and could help
to better focus quality assurance and testing activities. 相似文献
7.
Layered double hydroxides/epoxy (LDHs/EP) nanocomposites were prepared from organo-modified LDHs, a diglycidyl ether of bisphenol A monomer (DGEBA) and amine curing agents. The organo-modified LDHs were obtained by ionic exchange of a magnesium-aluminum carbonate LDH in an acid medium. X-ray diffraction and transmission electron microscopy showed a dispersion of the layers at a nanometer scale, indicating the formation of LDH/EP nanocomposites. The thermal degradation and flame resistance properties of LDH/EP nanocomposites, montmorillonite-epoxy (MMT/EP) nanocomposites, LDH/EP microcomposites and aluminum hydroxide-epoxy microcomposites were compared by thermogravimetrical analyses, simultaneous thermal analyses, UL94 and cone calorimeter tests. Only LDH/EP nanocomposites showed self-extinguishing behavior in the horizontal UL94 test; LDH/EP microcomposites and MMT/EP nanocomposites samples burned completely showing that the unique flame resistance of LDH/EP nanocomposites is related to both the level of dispersion and the intrinsic properties of LDH clay. Furthermore, cone calorimeter revealed intumescent behavior for LDH/EP nanocomposites and a higher reduction in the peak heat release rate compared to MMT/EP nanocomposites. 相似文献
8.
Giuseppe Ajroldi Maurizio Pianca Massimiliano Fumagalli Giovanni Moggi 《Polymer》1989,30(12):2180-2187
The dynamic-mechanical properties of some fluoroelastomers were determined as a function of composition at low frequency (≈ 1 Hz), by means of a free oscillation torsion pendulum, between −180°C and the softening point. Vinylidenefluoride (VDF)-hexafluoropropene (HFP) copolymers of molar composition 0–39% HFP and terpolymers of VDF and HFP with up to 30mol% tetrafluoroethylene (TFE) and a constant VDF to HFP molar ratio of 3.4 were considered. Two relaxation processes typical of the amorphous phase were found. The first, located at about −87°C, is related to local motions and the transition temperature was found to be independent of composition for copolymers, while it depends on TFE molar content for terpolymers. The second is related to the glass transition and the transition temperature depends on the composition. However, for semicrystalline copolymers the double glass transition phenomenon was observed. When crystallinity goes to zero at about 20 mol% HFP, only one transition is observed. It was also found that ordered structures can take place for terpolymers when TFE molar concentration exceeds 20%. The crystal disorder transition of pure PVDF (75°C) is observed also for low HFP concentrations but the transition temperature is strongly reduced. Analogies between the VDF-HFP and E-P systems are also discussed. 相似文献
9.
The event detection problem, which is closely related to clustering, has gained a lot of attentions within event detection for textual documents. However, although image clustering is a problem that has been treated extensively in both Content-Based Image Retrieval (CBIR) and Text-Based Image Retrieval (TBIR) systems, event detection within image management is a relatively new area. Having this in mind, we propose a novel approach for event extraction and clustering of images, taking into account textual annotations, time and geographical positions. Our goal is to develop a clustering method based on the fact that an image may belong to an event cluster. Here, we stress the necessity of having an event clustering and cluster extraction algorithm that are both scalable and allow online applications. To achieve this, we extend a well-known clustering algorithm called Suffix Tree Clustering (STC), originally developed to cluster text documents using document snippets. The idea is that we consider an image along with its annotation as a document. Further, we extend it to also include time and geographical position so that we can capture the contextual information from each image during the clustering process. This has appeared to be particularly useful on images gathered from online photo-sharing applications such as Flickr. Hence, our STC-based approach is aimed at dealing with the challenges induced by capturing contextual information from Flickr images and extracting related events. We evaluate our algorithm using different annotated datasets mainly gathered from Flickr. As part of this evaluation we investigate the effects of using different parameters, such as time and space granularities, and compare these effects. In addition, we evaluate the performance of our algorithm with respect to mining events from image collections. Our experimental results clearly demonstrate the effectiveness of our STC-based algorithm in extracting and clustering events. 相似文献
10.
Gerardo Canfora Luigi Cerulo Marta Cimitile Massimiliano Di Penta 《Empirical Software Engineering》2014,19(1):1-38
Context Software systems continuously change for various reasons, such as adding new features, fixing bugs, or refactoring. Changes may either increase the source code complexity and disorganization, or help to reducing it. Aim This paper empirically investigates the relationship of source code complexity and disorganization—measured using source code change entropy—with four factors, namely the presence of refactoring activities, the number of developers working on a source code file, the participation of classes in design patterns, and the different kinds of changes occurring on the system, classified in terms of their topics extracted from commit notes. Method We carried out an exploratory study on an interval of the life-time span of four open source systems, namely ArgoUML, Eclipse-JDT, Mozilla, and Samba, with the aim of analyzing the relationship between the source code change entropy and four factors: refactoring activities, number of contributors for a file, participation of classes in design patterns, and change topics. Results The study shows that (i) the change entropy decreases after refactoring, (ii) files changed by a higher number of developers tend to exhibit a higher change entropy than others, (iii) classes participating in certain design patterns exhibit a higher change entropy than others, and (iv) changes related to different topics exhibit different change entropy, for example bug fixings exhibit a limited change entropy while changes introducing new features exhibit a high change entropy. Conclusions Results provided in this paper indicate that the nature of changes (in particular changes related to refactorings), the software design, and the number of active developers are factors related to change entropy. Our findings contribute to understand the software aging phenomenon and are preliminary to identifying better ways to contrast it. 相似文献