1,589 research outputs found
The Creep Parameters of SAC305 Unleaded Solders
The tensile and shear loading creep parameters of unleaded Sn/3.0Ag/0.5Cu solders are extracted from the proposed tensile and shear creep tests in this work. Four creep loading temperatures, that is, , , , and C, are employed to extract the corresponding parameters. The creep parameters for tensile and shear loading models, that is, stress exponent, material constant, and activation energy, are curve-fitted by using the least square error and simplex optimization algorithms. The accuracy of the extracted parameters correlated with the measured strain rate versus temperature curves. Results indicate that the proposed measurement setup and extraction algorithm is feasible to extract the tensile and shear type creep parameters with good accuracy
Microfluidic-integrated laser-controlled microactuators with on-chip microscopy imaging functionality
The fabrication of a novel microfluidic system, integrated with a set of laser-controlled microactuators on an ePetri on-chip microscopy platform, is presented in this paper. In the fully integrated microfluidic system, a set of novel thermally actuated paraffin-based microactuators, precisely controlled by programmed laser optics, was developed to regulate flow and to provide pumping of liquid solutions without external connections. The microfluidic chip was fabricated on a complementary metal–oxide–semiconductor (CMOS)-imaging sensor chip on an ePetri platform; this configuration provided real-time, wide field-of-view, high-resolution imaging using a sub-pixel sweeping microscopy technique. The system of microactuators, which consisted of microvalves and a micropump, operated well in the microfluidic channel with a focused near-infrared laser beam providing the actuation control. As a demonstration, we used our prototype to assess cell–drug interactions and to monitor cell growth directly within an incubator in real time. The powerful combination of laser-actuated microfluidics and chip-scale microscopy techniques represents a significant step forward in terms of a simple, robust, high-throughput, and highly compact analysis system for biomedical and bioscience applications
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The melanocortin pathway and energy homeostasis: From discovery to obesity therapy.
BACKGROUND: Over the past 20 years, insights from human and mouse genetics have illuminated the central role of the brain leptin-melanocortin pathway in controlling mammalian food intake, with genetic disruption resulting in extreme obesity, and more subtle polymorphic variations influencing the population distribution of body weight. At the end of 2020, the U.S. Food and Drug Administration (FDA) approved setmelanotide, a melanocortin 4 receptor agonist, for use in individuals with severe obesity due to either pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. SCOPE OF REVIEW: Herein, we chart the melanocortin pathway's history, explore its pharmacology, genetics, and physiology, and describe how a neuropeptidergic circuit became an important druggable obesity target. MAJOR CONCLUSIONS: Unravelling the genetics of the subset of severe obesity has revealed the importance of the melanocortin pathway in appetitive control; coupling this with studying the molecular pharmacology of compounds that bind melanocortin receptors has brought a new obesity drug to the market. This process provides a drug discovery template for complex disorders, which for setmelanotide took 25 years to transform from a single gene into an approved drug
Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease
Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures
Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?
Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds
Constructal blade shape in nanofluids
Blade configuration of nanofluids has been proven to perform much better than dispersed configuration for some heat conduction systems. The analytical analysis and numerical calculation are made for the cylinder--shaped and regular-rectangular-prism--shaped building blocks of the blade-configured heat conduction systems (using nanofluids as the heat conduction media) to find the optimal cross-sectional shape for the nanoparticle blade under the same composing materials, composition ratio, volumetric heat generation rate, and total building block volume. The regular-triangular-prism--shaped blade has been proven to perform better than all the other three kinds of blades, namely, the regular-rectangular-prism--shaped blade, the regular-hexagonal-prism--shaped blade, and the cylinder--shaped blade. Thus, the regular-triangular-prism--shaped blade is selected as the optimally shaped blade for the two kinds of building blocks that are considered in this study. It is also proven that the constructal cylinder--regular-triangular-prism building block performs better than the constructal regular-rectangular-prism--regular-triangular-prism building block
A Non-coding RNA of Insect HzNV-1 Virus Establishes Latent Viral Infection through MicroRNA
Heliothis zea nudivirus-1 (HzNV-1) is an insect virus previously known as Hz-1 baculovirus. One of its major early genes, hhi1, is responsible for the establishment of productive viral infection; another gene, pag1, which expresses a non-coding RNA, is the only viral transcript detectable during viral latency. Here we showed that this non-coding RNA was further processed into at least two distinct miRNAs, which targeted and degraded hhi1 transcript. This is a result strikingly similar to a recent report that herpes simplex virus produces tightly-regulated latent specific miRNAs to silence its own key early transcripts. Nevertheless, proof for the establishment of viral latency by miRNA is still lacking. We further showed that HzNV-1 latency could be directly induced by pag1-derived miRNAs in cells infected with a pag1-deleted, latency-deficient virus. This result suggests the existence of a novel mechanism, where miRNAs can be functional for the establishment of viral latency
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