83 research outputs found

    Publisher Correction:Voices of biotech leaders (Nature Biotechnology, (2021), 39, 6, (654-660), 10.1038/s41587-021-00941-4)

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    In the version of this article initially published, an author name was given as Abasi Ene Abong. The correct name is Abasi Ene-Obong. Also, the affiliation for Sebastian Giwa was given as Elevian, Pagliuca Harvard Life Lab, Allston, MA, USA. The correct affiliations are Biostasis Research Institute, Berkeley, CA, USA; Sylvatica Biotech, North Charleston, SC, USA; and Humanity Bio, Kensington, CA, USA. An affiliation for Jeantine Lunshof was given as Department of Genetics, Harvard Medical School, Boston, MA, USA. The correct affiliation is Wyss Institute for Biological Engineering, Harvard University, Boston, MA, USA. The errors have been corrected in the PDF and HTML versions of the article

    Mouse models of nesprin-related diseases

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    Nesprins (nuclear envelope spectrin repeat proteins) are a family of multi-isomeric scaffolding proteins. Nesprins form the LInker of Nucleoskeleton-and-Cytoskeleton (LINC) complex with SUN (Sad1p/UNC84) domain-containing proteins at the nuclear envelope, in association with lamin A/C and emerin, linking the nucleoskeleton to the cytoskeleton. The LINC complex serves as both a physical linker between the nuclear lamina and the cytoskeleton and a mechanosensor. The LINC complex has a broad range of functions and is involved in maintaining nuclear architecture, nuclear positioning and migration, and also modulating gene expression. Over 80 disease-related variants have been identified in SYNE-1/2 (nesprin-1/2) genes, which result in muscular or central nervous system disorders including autosomal dominant Emery–Dreifuss muscular dystrophy, dilated cardiomyopathy and autosomal recessive cerebellar ataxia type 1. To date, 17 different nesprin mouse lines have been established to mimic these nesprin-related human diseases, which have provided valuable insights into the roles of nesprin and its scaffold LINC complex in a tissue-specific manner. In this review, we summarise the existing nesprin mouse models, compare their phenotypes and discuss the potential mechanisms underlying nesprin-associated diseases

    Multiple Novel Nesprin-1 and Nesprin-2 Variants Act as Versatile Tissue-Specific Intracellular Scaffolds

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    <div><h3>Background</h3><p>Nesprins (<u>N</u>uclear <u>e</u>nvelope <u>s</u>pectrin-<u>r</u>epeat <u>p</u>roteins) are a novel family of giant spectrin-repeat containing proteins. The nesprin-1 and nesprin-2 genes consist of 146 and 116 exons which encode proteins of ∼1mDa and ∼800 kDa is size respectively when all the exons are utilised in translation. However emerging data suggests that the nesprins have multiple alternative start and termination sites throughout their genes allowing the generation of smaller isoforms.</p> <h3>Results</h3><p>In this study we set out to identify novel alternatively transcribed nesprin variants by screening the EST database and by using RACE analysis to identify cDNA ends. These two methods provided potential hits for alternative start and termination sites that were validated by PCR and DNA sequencing. We show that these alternative sites are not only expressed in a tissue specific manner but by combining different sites together it is possible to create a wide array of nesprin variants. By cloning and expressing small novel nesprin variants into human fibroblasts and U2OS cells we show localization to actin stress-fibres, focal adhesions, microtubules, the nucleolus, nuclear matrix and the nuclear envelope (NE). Furthermore we show that the sub-cellular localization of individual nesprin variants can vary depending on the cell type, suggesting any single nesprin variant may have different functions in different cell types.</p> <h3>Conclusions</h3><p>These studies suggest nesprins act as highly versatile tissue specific intracellular protein scaffolds and identify potential novel functions for nesprins beyond cytoplasmic-nuclear coupling. These alternate functions may also account for the diverse range of disease phenotypes observed when these genes are mutated.</p> </div

    Identification of unique SUN-interacting nuclear envelope proteins with diverse functions in plants

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    Although a plethora of nuclear envelope (NE) transmembrane proteins (NETs) have been identified in opisthokonts, plant NETs are largely unknown. The only known NET homologues in plants are Sad1/UNC-84 (SUN) proteins, which bind Klarsicht/ANC-1/Syne-1 homology (KASH) proteins. Therefore, de novo identification of plant NETs is necessary. Based on similarities between opisthokont KASH proteins and the only known plant KASH proteins, WPP domain–interacting proteins, we used a computational method to identify the KASH subset of plant NETs. Ten potential plant KASH protein families were identified, and five candidates from four of these families were verified for their NE localization, depending on SUN domain interaction. Of those, Arabidopsis thaliana SINE1 is involved in actin-dependent nuclear positioning in guard cells, whereas its paralogue SINE2 contributes to innate immunity against an oomycete pathogen. This study dramatically expands our knowledge of plant KASH proteins and suggests that plants and opisthokonts have recruited different KASH proteins to perform NE regulatory functions

    Feasibility analysis of a two-phase solar thermal water heater

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    Experiments were conducted to measure the heat transfer characteristics of nonboiling two-phase segmented flow in a solar thermal collector. The solar thermal collector was manufactured to have a serpentine flow path (residential serpentine deign) and the diameter of collector pipe was 0.0109 m. The working fluids used in the experiments were water, ethylene glycol and air. Single phase water was examined first, and the results were used as a basis for comparison for the water-air two-phase flow results. Two-phase experiments using ethylene glycol-air and single phase ethylene glycol were then conducted. The flow rates of the water-air and ethylene glycol-air phases were varied between a range of values during each experiment and the system pressure and temperatures were recorded at each combination of flow rates. The experimental data was used to calculate the number of variables, such as the heat transfer rate Q , temperature difference between the entrance and exit of the solar thermal collector [delta]T , average bulk temperature b T , the time required for raising the temperature inside the tank from 25℃ to 70℃, and the energy gained from the tank E . It has been shown that the heat transfer enhancement of two-phase flow system was better than the single phase flow system. Several experiments were conducted to study the effects of liquid void fraction αl. The effect of liquid void fraction showed that the heat transfer rate was highest in all experiments when the liquid void fraction was 0.5, while the heat transfer rate was at its lowest value when the liquid void fraction was 0.79. The effect of void fraction was found to be a controlling factor due to its impact on liquid slug length, which in turn affects the heat transfer rate. Finally, the four two-phase experiments were compared with single phase flow experiment. The result illustrated that the two-phase flow system was better than the single phase flow system

    Neural Network Demodulator For Quadrature Amplitude Modulation (Qam)

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    Artificial Neural Network (ANN) adalah salah satu bidang teknologi paling canggih, yang memungkinkan mesin belajar dari contoh dengan cara yang mirip dengan pembelajaran otak manusia. Ann diterapkan pada banyak bidang seperti pendekatan fungsi, pemrosesan data, klasifikasi, demodulasi sinyal dan banyak lagi. Masalah utama di bidang komunikasi adalah efek dari kebisingan ke dalam sinyal. Dalam tesis ini, demodulator jaringan saraf tiruan (NND) untuk mendemodulasi sinyal modulasi amplitude amplitude (QAM) diusulkan, proyek ini berupaya mengembangkan sistem komunikasi dengan mengembangkan jaringan saraf dan pembelajaran mesin. Proyek ini akan membantu memberikan kontribusi untuk mengurangi bit kesalahan, mengoptimalkan kualitas data yang diterima dan mengoptimalkan (NNDS)

    The effect of shear blocks in OSB double layer gridshells

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    Bending active gridshells result from made by deforming, usually on site, an initially flat grid composed of straight members into a 3 dimensional curved shape. A timber bending active gridshell sufficiently stiff for even a long span may be assembled from individual flexible layers. Each grid layer is independently deformed into a 3-D curved shape. The layers are then locked together using shear blocks to form a stiff and strong composite structural unit. Bending active timber gridshells require long defect-free lengths (to avoid fracture during forming) and small member cross-sections (for flexibility). The use of solid timber laths usually involves costly processing to cut out defects and re-join the pieces. This study examines an engineered timber product, Irish Orientated Strand Board [OSB], which promises to address these difficulties. This research investigates the degree of composite action generated by shear blocks in a double layer bending active gridshell made from Irish OSB. The study also investigates the material stiffness of OSB. Gridshell behaviour is typically geometrically non-linear and depends on the forming process. Computer analysis can address both issues. It is convenient in such computer models to treat a multi-layer grid as a single layer grid of equivalent stiffness. This equivalent stiffness depends on the effect of the shear blocks. Collins has established a global value for the degree of composite action (and hence an equivalent bending stiffness) for best fit of experimental deflection data with model predictions in a double curved Irish OSB experimental gridshell. However Collins did not investigate directly the degree of composite action in individual members. This research investigates the degree of composite action of individual flat double layer strips of Irish OSB and compares these with the best-fit global value noted by Collin’s. Significant differences from Collins’ value are noted and possible explanations discussed. Suggestions for further research are described

    Positioning nuclei within the cytoplasm of striated muscle fiber

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