761 research outputs found

    Involvement of miR-106b in tumorigenic actions of both prolactin and estradiol.

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    Prolactin promotes a variety of cancers by an array of different mechanisms. Here, we have investigated prolactin's inhibitory effect on expression of the cell cycle-regulating protein, p21. Using a miRNA array, we identified a number of miRNAs upregulated by prolactin treatment, but one in particular that was strongly induced by prolactin and predicted to bind to the 3'UTR of p21 mRNA, miR-106b. By creating a p21 mRNA 3'UTR-luciferase mRNA construct, we demonstrated degradation of the construct in response to prolactin in human breast, prostate and ovarian cancer cell lines. Increased expression of miR-106b replicated, and anti-miR-106b counteracted, the effects of prolactin on degradation of the 3'UTR construct, p21 mRNA levels, and cell proliferation in breast (T47D) and prostate (PC3) cancer cells. Increased expression of miR-106b also stimulated migration of the very epithelioid T47D cell line. By contrast, anti-miR-106b dramatically decreased expression of the mesenchymal markers, SNAIL-2, TWIST-2, VIMENTIN, and FIBRONECTIN. Using signaling pathway inhibitors and the 3'UTR construct, induction of miR-106b by prolactin was determined to be mediated through the MAPK/ERK and PI3K/Akt pathways and not through Jak2/Stat5 in both T47D and PC3 cells. Prolactin activation of MAPK/ERK and PI3K/Akt also activates ERα in the absence of an ERα ligand. 17β-estradiol promoted degradation of the construct in both cell lines and pre-incubation in the estrogen antagonist, Fulvestrant, blocked the ability of both prolactin and 17β-estradiol to induce the construct-degrading activity. Together, these data support a convergence of the prolactin and 17β-estradiol miR-106b-elevating signaling pathways at ERα

    The nuclear envelopathies and human diseases

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    The nuclear envelope (NE) consists of two membrane layers that segregate the nuclear from the cytoplasmic contents. Recent progress in our understanding of nuclear-lamina associated diseases has revealed intriguing connections between the envelope components and nuclear processes. Here, we review the functions of the nuclear envelope in chromosome organization, gene expression, DNA repair and cell cycle progression, and correlate deficiencies in envelope function with human pathologies

    A Study on the Misallocation Effect of Capital Combination on China’s High-tech Industry

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    387-390This paper aims to investigate the misallocation effect of different capital combinations accumulated from R&D and non-R&D activity in China’s high-tech industry. Using a conceptual model, the study first establishes an equilibrium combination derived from the firm’s behavior, and then analyzes the misallocation situation in China’s high-tech industry from 2003–2016. The findings indicate that the misallocation effect becomes clearer in the Chinese high-tech industry as input increases, and increased non-R&D activity worsens the misallocation

    Kinetic Modeling for Microwave-Enhanced Degradation of Methylene Blue Using Manganese Oxide

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    This study was originally performed to compare the MnO2-based degradation of aqueous methylene blue (MB) under microwave irradiation- (MW-) enhanced and conventional heating- (CH-) enhanced conditions. The degradation process and kinetics were investigated to elucidate the microwave effect on the reaction. The results showed that all three tested conditions, sole MnO2, MnO2/CH, and MnO2/MW, followed the third-order (second upon MB and first upon MnO2) kinetic model. However, a higher degradation rate of MB was available under the MW-enhanced process, which implies that the “athermal effect” of MW might be of more benefit for the generation of electrophilic oxygen ions (, , and ) to degrade MB. The results showed that the degradation percentage of MB could reach 100%, corresponding to 92% total organic carbon (TOC) removal under microwave irradiation at pH 7.20 for 10 min

    Cyclosporine A Eye Drop-Induced Elongated Eyelashes: A Case Report

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    Purpose: The most common ocular adverse event following the use of cyclosporine A (CsA) 0.05% ophthalmic emulsion is ocular burning (17%). Other adverse effects that have been reported include conjunctival hyperemia (1–5%), discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging and blurred vision. Here, we report a specific side effect of CsA, namely eye drop-induced eyelash elongation in a patient with refractory giant papillary conjunctivitis. Design: Observational case report. Methods: Case report and review of the literature. Results: A 32-year-old female with giant papillary conjunctivitis on the left eye, who had undergone papillectomy 3 years previously and was refractory to topical steroid therapy, was treated with CsA 0.05% ophthalmic emulsion (Restasis) 4 times a day, preservative-free artificial tears and gentamicin ophthalmic solution in the left eye. After 5 months of topical CsA treatment, elongated eyelashes of her left eye were observed without other adverse effects. Conclusion: Although hypertrichosis and trichomegaly have been documented in the literature as side effects of systemic CsA, topical CsA 0.05% eye drop-induced elongated eyelashes have not been reported, and we believe ophthalmologists should be mindful and inform patients about this specific side effect

    Open dataset of 20 interviews with senior service designers and managers for the Empathy Business research project

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    The aim of the Empathy Business research project (2023-2024) led by the University of Lapland focused on how to digitalize services and business prototyping through creativity. The research named challenges as well as design methods for developing digital tools for meeting the future needs of service design and business development. In total, 20 interviews among senior service designers and managers located in Europe, Latin America and Asia were conducted during spring 2023. The interviews provide perspectives related to the future of service design as a practise, the skills required and further issues of relevance for professionals in the field. Based on affinity diagramming eight main clusters were named: Sustainability, Business compatibility, New tools, Designer’s skills, Art-based methods, People in the centre, Online workshops, and Physical workshops. This data set includes an anonymized list of the interviewees, affinity diagram post-it notes of the interviews, short descriptions of the main clusters and an internet link to the online affinity diagram on Miro board. The materials provided initial insights for developing Proof-of-Concepts for digitized interfaces, such as suitable plugins, 3D-based photorealistic solutions, or an application with the potential to be used in service design and service prototyping contexts as well as in other development processes within and across organizations

    Simulation Environment with Customized RISC-V Instructions for Logic-in-Memory Architectures

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    Nowadays, various memory-hungry applications like machine learning algorithms are knocking "the memory wall". Toward this, emerging memories featuring computational capacity are foreseen as a promising solution that performs data process inside the memory itself, so-called computation-in-memory, while eliminating the need for costly data movement. Recent research shows that utilizing the custom extension of RISC-V instruction set architecture to support computation-in-memory operations is effective. To evaluate the applicability of such methods further, this work enhances the standard GNU binary utilities to generate RISC-V executables with Logic-in-Memory (LiM) operations and develop a new gem5 simulation environment, which simulates the entire system (CPU, peripherals, etc.) in a cycle-accurate manner together with a user-defined LiM module integrated into the system. This work provides a modular testbed for the research community to evaluate potential LiM solutions and co-designs between hardware and software
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