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排序方式: 共有294条查询结果,搜索用时 15 毫秒
1.
Elisa Mascolo Francesco Liguori Lorenzo Stufera Mecarelli Noemi Amoroso Chiara Merigliano Susanna Amadio Cinzia Volont Roberto Contestabile Angela Tramonti Fiammetta Vernì 《International journal of molecular sciences》2021,22(2)
Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity. 相似文献
2.
This paper presents a model of labor participation calibrated on a weekly basis; part-time and full-time employments are also
considered. By applying the theory of random utility maximization we model households’ choices. In order to have a good temporal
and spatial coverage the model is calibrated on three datasets, extracted from both national and regional travel surveys.
The results are applied to synthetic households that reproduce the Belgian population. The proposed innovative methodology
simulates synthetic agents by accounting both for households’ and individuals’ characteristics, while not suffering from the
problem of the “zero cell value”. The results indicate that there is major day-to-day variability in working activity participation;
in particular, on Wednesdays and Fridays the number of households working part-time or not working is particularly high. This
is consistent with what was expected by the analysts. Working participation is a fundamental component in activity based models
where work is considered a skeletal activity. The tools developed here can be useful to study how changes in population characteristics
(i.e. increases of flexible working arrangements and of the number of women in the work force) affect activity participation
and travel patterns. 相似文献
3.
Margaret Ottaviano Emilio Francesco Giunta Marianna Tortora Marcello Curvietto Laura Attademo Davide Bosso Cinzia Cardalesi Mario Rosanova Pietro De Placido Erica Pietroluongo Vittorio Riccio Brigitta Mucci Sara Parola Maria Grazia Vitale Giovannella Palmieri Bruno Daniele Ester Simeone 《International journal of molecular sciences》2021,22(7)
As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients. 相似文献
4.
Valter Castelvetro Cinzia De Vita Giacomo Giannini Simone Giaiacopi 《应用聚合物科学杂志》2006,102(4):3083-3094
The evolution of the main colloidal parameters in the seeded starved‐feed semi‐continuous emulsion polymerization of butyl methacrylate (BMA) was investigated, with the main purpose of assessing the effectiveness of the semi‐empirical relationship S = K · SS · ΔA/AS as a tool to define the surfactant/monomer feed ratio (∝ K) best suited to achieve a target particle size. In particular, the effect of the type and amount of surfactant [i.e., anionic, sodium dodecyl sulfate (SDS), or nonionic, Brij 58P] added during the semi‐continuous stage was considered. Coagulum formation was never observed under the adopted experimental conditions. To detect the occurrence of secondary nucleation or particle aggregation, or both, the particle size and number of particles, the surface tension and the particle surface coverage ratio were correlated. The best results were obtained with SDS and 0.8 ≤ K ≤ 3. In fact, under the selected experimental conditions, only with SDS did the number of particles remain nearly constant throughout the polymerization at the value defined by the seed latex; the particle size distribution was highly monodisperse, and the final particle diameter closely matched the calculated one (~ 120 nm). The above semi‐empirical relationship based on the adjustable parameter K was validated by running test polymerizations aimed at lattices with well‐defined particle size. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3083–3094, 2006 相似文献
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7.
The multimod application framework: a rapid application development tool for computer aided medicine 总被引:1,自引:0,他引:1
Viceconti M Zannoni C Testi D Petrone M Perticoni S Quadrani P Taddei F Imboden S Clapworthy G 《Computer methods and programs in biomedicine》2007,85(2):138-151
This paper describes a new application framework (OpenMAF) for rapid development of multimodal applications in computer-aided medicine. MAF applications are multimodal in data, in representation, and in interaction. The framework supports almost any type of biomedical data, including DICOM datasets, motion-capture recordings, or data from computer simulations (e.g. finite element modeling). The interactive visualization approach (multimodal display) helps the user interpret complex datasets, providing multiple representations of the same data. In addition, the framework allows multimodal interaction by supporting the simultaneous use of different input-output devices like 3D trackers, stereoscopic displays, haptics hardware and speech recognition/synthesis systems. The Framework has been designed to run smoothly even on limited power computers, but it can take advantage of all hardware capabilities. The Framework is based on a collection of portable libraries and it can be compiled on any platform that supports OpenGL, including Windows, MacOS X and any flavor of Unix/linux. 相似文献
8.
Giancarlo Paganin Adriana Angelotti Chiara Ducoli Monica Lavagna Cinzia Talamo Stefano Luccietto 《Energy Efficiency》2017,10(6):1343-1364
Nowadays, the focus on the building energy consumption in the use phase prevails over an interest concerning the energy impacts linked to all the other phases of the construction process. However, reducing operational energy could lead to shifting the impacts from one stage to another. Thus, combining the study of strategies improving energy efficiency in the use phase with a life cycle approach is crucial. Exhibition halls are peculiar buildings from the geometry, construction and use points of view, rarely addressed in energy and life cycle energy analysis studies. Therefore, in this paper, a representative hall of the Milan Trade Fair is taken as a case study. A building energy simulation model is firstly calibrated in order to derive the operational energy for climatisation. The operational energy appears artificially low due to the short use period during the year. When compared with the calculated embodied energy of the envelope and structure, it is found that 57 years would be needed to balance energy spent in the construction and in the use phase. Further, some retrofit interventions are proposed and analyzed. Insulation interventions are not attractive from the economic payback time point of view. However, when the embodied energy of the retrofit interventions is compared with the energy savings in the use phase, interesting energy payback times are obtained. Therefore, this study puts in evidence on the importance of adopting a life cycle perspective, especially for buildings with low-intensity use. Eventually, the critical issues of the life cycle energy analysis are deeply discussed. 相似文献
9.
Cinzia Stigliano Melissa D. Landis Daniel Y. Lee Paolo Decuzzi 《Small (Weinheim an der Bergstrasse, Germany)》2014,10(13):2688-2696
Hybrid PET/MRI scanners have the potential to provide fundamental molecular, cellular, and anatomic information essential for optimizing therapeutic and surgical interventions. However, their full utilization is currently limited by the lack of truly multi‐modal contrast agents capable of exploiting the strengths of each modality. Here, we report on the development of long‐circulating positron‐emitting magnetic nanoconstructs (PEM) designed to image solid tumors for combined PET/MRI. PEMs are synthesized by a modified nano‐precipitation method mixing poly(lactic‐co‐glycolic acid) (PLGA), lipids, and polyethylene glycol (PEG) chains with 5 nm iron oxide nanoparticles (USPIOs). PEM lipids are coupled with 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) and subsequently chelated to 64Cu. PEMs show a diameter of 140 ± 7 nm and a transversal relaxivity r2 of 265.0 ± 10.0 (mM × s)?1, with a r2/r1 ratio of 123. Using a murine xenograft model bearing human breast cancer cell line (MDA‐MB‐231), intravenously administered PEMs progressively accumulate in tumors reaching a maximum of 3.5 ± 0.25% ID/g tumor at 20 h post‐injection. Correlation of PET and MRI signals revealed non‐uniform intratumoral distribution of PEMs with focal areas of accumulation at the tumor periphery. These long‐circulating PEMs with high transversal relaxivity and tumor accumulation may allow for detailed interrogation over multiple scales in a clinically relevant setting. 相似文献
10.
Serena Silvestro Cinzia Sindona Placido Bramanti Emanuela Mazzon 《International journal of molecular sciences》2021,22(6)
Neurodegenerative diseases represent a set of pathologies characterized by an irreversible and progressive, and a loss of neuronal cells in specific areas of the brain. Oxidative phosphorylation is a source of energy production by which many cells, such as the neuronal cells, meet their energy needs. Dysregulations of oxidative phosphorylation induce oxidative stress, which plays a key role in the onset of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). To date, for most neurodegenerative diseases, there are no resolute treatments, but only interventions capable of alleviating the symptoms or slowing the course of the disease. Therefore, effective neuroprotection strategies are needed. In recent years, natural products, such as curcuminoids, have been intensively explored and studied for their therapeutic potentials in several neurodegenerative diseases. Curcuminoids are, nutraceutical compouns, that owen several therapeutic properties such as anti-oxidant, anti-inflammatory and neuroprotective effects. In this context, the aim of this review was to provide an overview of preclinical and clinical evidence aimed to illustrate the antioxidant effects of curcuminoids in neurodegenerative diseases. Promising results from preclinical studies encourage the use of curcuminoids for neurodegeneration prevention and treatment. 相似文献