The expression and localization of cytoplasmic polyadenylation element binding proteins in the retina.

The current status of our knowledge of synaptic plasticity comes largely from studies of the hippocampus and the context of learning and memory. We remain largely ignorant of plasticity in other neural systems and contexts. The molecular basis of plasticity has recently been given new impetus due to the discovery of a local control mechanism which can regulate protein synthesis at stimulated synapses. This involves the use of cytoplasmic polyadenylation binding proteins (CPEBs) to regulate translation. The studies presented here attempt to show that these molecular components are present in the retina, a part of the central nervous system that has been seen, historically, as not plastic. Methods used. RT-PCR was used to determine the presence of mRNAs in tissue. In situ hybridization and immunofluorescence microscopy were used for localization of mRNAs and proteins respectively. Real-time PCR and Western blots were used for quantifications of mRNA and proteins during postnatal development. A bioinformatics program CPE detector and 3\u27 RACE were used to identify potential mRNA targets for CPEB1 in the UTR databases and in the retina respectively. The PAT assay was used to determine the length of poly(A) tails for some potential mRNA targets. Data mining and sequence alignment were used to identify alternatively spliced isoforms of CPEB3. Major results. Our results demonstrated that CPEB1-4 were all present in the retina. The four CPEBs had similar distributions in the inner retina: predominantly in the retinal ganglion cell layer, and to a less extent, in the inner nuclear layer. However, CPEB1 had a laminar pattern in the inner plexiform layer, whereas CPEB3 was diffuse. The presence of CPEB1 was minimal in the outer plexiform layer in contrast to CPEB3. During postnatal development the levels of CPEB1, 3 and 4 were up-regulated; whereas the level of CPEB2 was constant. Potential mRNAs were identified as targets of CPEB1; some mRNA targets demonstrated elongated poly(A) tails at postnatal day7 or day12, consistent with the up-regulation of CPEB1 at these ages. Multiple isoforms, including a novel one, were identified for CPEB3. The alternative splicing of CPEB3 could occur both in the UTRs and in the coding region. Major conclusions/significance. Our data demonstrated that more than one CPEB paralog is present in mouse retina. Potential mRNA targets for CPEB1 were present in the retina and gained elongated poly(A) tail in accordance with the up-regulation of CPEB1 during development. The increases of CPEB1, 3 and 4 during the development indicate a possible role of such CPEBs in synaptogenesis. Continuing up-regulation of CPEB1, 3 and 4 also indicate a role in the adult retina. Alternative splicing in the UTRs of CPEB3 indicates a complex regulation of CPEB3; multiple isoforms of CPEB3 protein indicate the functional complexity of CPEB3. The presence of CPEBs in the retina indicates the existence of a translational control system in the retina. Future studies. Future studies should focus on the identification of mRNA targets for each CPEB. Such potential targets can be validated using in vitro binding assays to confirm their interaction with CPEB proteins. CPEB can be knocked-down or overexpressed in cultured cells. CPEB knockout mice can be generated for further functional studies

Adaptive Slicing for Multi-Axis Hybrid Plasma Deposition and Milling

Hybrid Plasma Deposition and Milling (HPDM), a five-axis manufacturing system integrated material additive and subtractive processes, can be used to create overhang metallic components directly without the usage of sacrificial support structure. Different from conventional slicing methods, a new slicing algorithm with changeable direction and thickness is proposed in this paper. Minimal overhang length is selected as the objective function to optimize the build direction. The thickness is adjusted to meet allowable overhang length and allowable cups height. The input mesh is first decomposed into non-uniform thickness segment meshes and then each segment is cut into uniform thickness slices. The output slices consist of split slices between two adjacent segment meshes and inner slices for each segment mesh. Examples and analyses confirm the feasibility and effectiveness.Mechanical Engineerin

Electromagnetic imaging and deep learning for transition to renewable energies: a technology review

Electromagnetic imaging is a technique that has been employed and perfected to investigate the Earth subsurface over the past three decades. Besides the traditional geophysical surveys (e.g., hydrocarbon exploration, geological mapping), several new applications have appeared (e.g., characterization of geothermal energy reservoirs, capture and storage of carbon dioxide, water prospecting, and monitoring of hazardous-waste deposits). The development of new numerical schemes, algorithms, and easy access to supercomputers have supported innovation throughout the geo-electromagnetic community. In particular, deep learning solutions have taken electromagnetic imaging technology to a different level. These emerging deep learning tools have significantly contributed to data processing for enhanced electromagnetic imaging of the Earth. Herein, we review innovative electromagnetic imaging technologies and deep learning solutions and their role in better understanding useful resources for the energy transition path. To better understand this landscape, we describe the physics behind electromagnetic imaging, current trends in its numerical modeling, development of computational tools (traditional approaches and emerging deep learning schemes), and discuss some key applications for the energy transition. We focus on the need to explore all the alternatives of technologies and expertise transfer to propel the energy landscape forward. We hope this review may be useful for the entire geo-electromagnetic community and inspire and drive the further development of innovative electromagnetic imaging technologies to power a safer future based on energy sources.This work was supported by the European Union’s Horizon 2020 research and innovation programme under grant agreements No. 955606 (DEEP-SEA) and No. 777778 (MATHROCKS). Furthermore, the research leading of this study has received funding from the Ministerio de Educación y Ciencia (Spain) under Project TED2021-131882B-C42.Peer ReviewedPostprint (published version

Comparison between anterolateral thigh perforator free flaps and pectoralis major pedicled flap for reconstruction in oral cancer patients-A quality of life analysis

The aim of this study was to compare the differences between anterolateral thigh perforator free flaps (ALTFF) and pectoralis major myocutaneous flap (PMMF) for reconstruction in oral cancer patients. Method and Patients: who received free flap or PMMF reconstruction after ablation surgeries were eligible for the current study. The patients' demographic data, medical history, and quality of life scores(Medical Outcomes Study-Short Form-36 (MOS SF-36) and the University of Washington Quality of Life (UW-QOL) questionnaires were collected. Results: 81 of 118 questionnaires were returned (68.64%). There was signi.cant differences between two groups in the gender (P<0.005). Patients reconstructed with ALTFF had better appearance domains and better shoulders domains, in addition to better role emotion domains. Conclusions: Using either PMMF or ALTFF for reconstruction of oral defects after cancer resection signi.cantly in.uences a patient's quality of life. Data from this study provide useful information for physicians and patients during their discussion of reconstruction modalities for oral cancers

Pulsar discovery prospect of FASTA

The Five-hundred-meter Aperture Spherical radio Telescope (FAST) has discovered more than 650 new pulsars, which account for 20% of our known Galactic pulsar population. In this paper, we estimate the prospect of a pulsar survey with a radio telescope array to be planned -- the FAST Array (FASTA), consists of six "FAST-type" telescopes. Such a sensitive radio telescope array would be a powerful instrument in probing the pulsar population deep into our Galaxy as well as in nearby galaxies. We simulate the FASTA pulsar discovery prospects with different Galactic pulsar population models and instrumental parameter combinations. We find that FASTA could detect tens of thousands of canonical pulsars and well-over thousands of millisecond pulsars. We also estimate the potential yield if the FASTA is used to search for pulsars from the nearby spiral galaxy M31, and find that it would probably discover around a hundred new radio pulsars

A Novel Wide-Area Backup Protection Based on Fault Component Current Distribution and Improved Evidence Theory

In order to solve the problems of the existing wide-area backup protection (WABP) algorithms, the paper proposes a novel WABP algorithm based on the distribution characteristics of fault component current and improved Dempster/Shafer (D-S) evidence theory. When a fault occurs, slave substations transmit to master station the amplitudes of fault component currents of transmission lines which are the closest to fault element. Then master substation identifies suspicious faulty lines according to the distribution characteristics of fault component current. After that, the master substation will identify the actual faulty line with improved D-S evidence theory based on the action states of traditional protections and direction components of these suspicious faulty lines. The simulation examples based on IEEE 10-generator-39-bus system show that the proposed WABP algorithm has an excellent performance. The algorithm has low requirement of sampling synchronization, small wide-area communication flow, and high fault tolerance

Im/possible Lives: Gender, Class, Self-Fashioning, and Affinal Solidarity in Modern South Asia

Drawing on ethnographic research and employing a micro-historical approach that recognizes not only the transnational but also the culturally specific manifestations of modernity, this article centers on the efforts of a young woman to negotiate shifting and conflicting discourses about what a good life might consist of for a highly educated and high caste Hindu woman living at the margins of a nonetheless globalized world. Newly imaginable worlds in contemporary Mithila,South Asia, structure feeling and action in particularly gendered and classed ways, even as the capacity of individuals to actualize those worlds and the “modern” selves envisioned within them are constrained by both overt and subtle means. In the context of shifting cultural anchors, new practices of silence, literacy, and even behaviors interpreted as “mental illness” may become tactics in an individual’s negotiation of conflicting self-representations. The confluence of forces at play in contemporary Mithila, moreover, is creating new structures of feeling that may begin to reverse long-standing locally held assumptions about strong solidarities between natal families and daughters, on the one hand, and weak solidarities between affinal families and new daughters-in-law, on the other

Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment

<p>Abstract</p> <p>Background</p> <p>While all anti-diabetic agents can decrease blood glucose level directly or indirectly, few are able to protect and preserve both pancreatic beta cell mass and their insulin-secreting functions. Thus, there is an urgent need to find an agent or combination of agents that can lower blood glucose and preserve pancreatic beta cells at the same time. Herein, we report a dual-functional andrographolide-lipoic acid conjugate (AL-1). The anti-diabetic and beta cell protective activities of this novel andrographolide-lipoic acid conjugate were investigated.</p> <p>Methods</p> <p>In alloxan-treated mice (a model of type 1 diabetes), drugs were administered orally once daily for 6 days post-alloxan treatment. Fasting blood glucose and serum insulin were determined. Pathologic and immunohistochemical analysis of pancreatic islets were performed. Translocation of glucose transporter subtype 4 in soleus muscle was detected by western blot. In RIN-m cells <it>in vitro</it>, the effect of AL-1 on H₂O₂-induced damage and reactive oxidative species production stimulated by high glucose and glibenclamide were measured. Inhibition of nuclear factor kappa B (NF-κB) activation induced by IL-1β and IFN-γ was investigated.</p> <p>Results</p> <p>In alloxan-induced diabetic mouse model, AL-1 lowered blood glucose, increased insulin and prevented loss of beta cells and their dysfunction, stimulated glucose transport protein subtype 4 (GLUT4) membrane translocation in soleus muscles. Pretreatment of RIN-m cells with AL-1 prevented H₂O₂-induced cellular damage, quenched glucose and glibenclamide-stimulated reactive oxidative species production, and inhibited cytokine-stimulated NF-κB activation.</p> <p>Conclusion</p> <p>We have demonstrated that AL-1 had both hypoglycemic and beta cell protective effects which translated into antioxidant and NF-κB inhibitory activity. AL-1 is a potential new anti-diabetic agent.</p