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Melatonin is of great importance for regulating several eye processes, including pressure homeostasis. Melatonin in combination with agomelatine has been recently reported to reduce intraocular pressure (IOP) with higher efficacy than each compound alone. Here, we used the methylcellulose (MCE) rat model of hypertensive glaucoma, an optic neuropathy characterized by the apoptotic death of retinal ganglion cells (RGCs), to evaluate the hypotensive and neuroprotective efficacy of an eye drop nanomicellar formulation containing melatonin/agomelatine. Eye tissue distribution of melatonin/agomelatine in healthy rats was evaluated by HPLC/MS/MS. In the MCE model, we assessed by tonometry the hypotensive efficacy of melatonin/agomelatine. Neuroprotection was revealed by electroretinography; by levels of inflammatory and apoptotic markers; and by RGC density. The effects of melatonin/agomelatine were compared with those of timolol (a beta blocker with prevalent hypotensive activity) or brimonidine (an alpha 2 adrenergic agonist with potential neuroprotective efficacy), two drugs commonly used to treat glaucoma. Both melatonin and agomelatine penetrate the posterior segment of the eye. In the MCE model, IOP elevation was drastically reduced by melatonin/agomelatine with higher efficacy than that of timolol or brimonidine. Concomitantly, gliosis-related inflammation and the Bax-associated apoptosis were partially prevented, thus leading to RGC survival and recovered retinal dysfunction. We suggest that topical melatoninergic compounds might be beneficial for ocular health.  相似文献   
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This paper introduces a simple design strategy to increase the power efficiency of linear charge pumps. The technique exploits a voltage amplitude of the clock signal lower than the supply voltage to reduce the power conversion losses. The nominal output voltage is maintained unaltered by increasing the number of stages.  相似文献   
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DNA-encoded chemical libraries are often used for the discovery of ligands against protein targets of interest. These large collections of DNA-barcoded chemical compounds are typically screened by using affinity capture methodologies followed by PCR amplification and DNA sequencing procedures. However, the performance of individual steps in the selection procedures has been scarcely investigated, so far. Herein, the quantitative analysis of selection experiments, by using three ligands with different affinity to carbonic anhydrase IX as model compounds, is described. In the first set of experiments, quantitative PCR (qPCR) procedures are used to evaluate the recovery and selectivity for affinity capture procedures performed on different solid-phase supports, which are commonly used for library screening. In the second step, both qPCR and analysis of DNA sequencing results are used to assess the recovery and selectivity of individual carbonic anhydrase IX ligands in a library, containing 360 000 compounds. Collectively, this study reveals that selection procedures can be efficient for ligands with sub-micromolar dissociation constants to the target protein of interest, but also that selection performance dramatically drops if 104 copies per library member are used as the input.  相似文献   
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This work deals with the effect of build orientation and of allowance for machining on DMLS‐produced Maraging Steel MS1. The experimental results, arranged by tools of Design of Experiment, have been statistically processed and compared. The outcomes were that, probably due to effect of the thermal treatment, machining, and material properties, the aforementioned factors do not have a significant impact on the fatigue response. This made it possible to work out a global curve that accounts for all the results, consisting in a high amount of data points. This can be regarded as one of the most complete and reliable fatigue models in the current literature. Fractographic and micrographic studies have been performed as well, to individuate the crack initiation points, usually located at subsurface porosities, and to investigate the location of internal inclusions and the actual martensitic microstructure along the stacking direction and on the build plane.  相似文献   
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Robotic technologies, whether they are remotely operated vehicles, autonomous agents, assistive devices, or novel control interfaces, offer many promising capabilities for deployment in real‐world environments. Postdisaster scenarios are a particularly relevant target for applying such technologies, due to the challenging conditions faced by rescue workers and the possibility to increase their efficacy while decreasing the risks they face. However, field‐deployable technologies for rescue work have requirements for robustness, speed, versatility, and ease of use that may not be matched by the state of the art in robotics research. This paper aims to survey the current state of the art in ground and aerial robots, marine and amphibious systems, and human–robot control interfaces and assess the readiness of these technologies with respect to the needs of first responders and disaster recovery efforts. We have gathered expert opinions from emergency response stakeholders and researchers who conduct field deployments with them to understand these needs, and we present this assessment as a way to guide future research toward technologies that will make an impact in real‐world disaster response and recovery.  相似文献   
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