289 research outputs found

    Ultra-narrow (sub-MHz) linewidth emission from discrete mode laser diodes

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    A class of laser which exhibits ultra-narrow sub MHz linewidth emission necessary for numerous applications in optical communications and sensors is described. The spectral performance of commercial discrete mode (DM) and distributed feedback (DFB) lasers is compared. The devices used in this work are asymmetrically coated ridge waveguide Fabry Perot lasers which incorporated etched slot features and emitting around lambda = 1.55 mum. The active region of the devices consisted of a strained compensated InAlGaAs MQW structure

    Epigenetic variability is a modifier of facioscapulohumeral muscular dystrophy

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    Facioscapulohumeral muscular dystrophy (FSHD), the most prevalent myopathy afflicting both children and adults, is strongly associated with epigenetic changes of the 4q35-localized macrosatellite D4Z4 repeat. Recent studies propose that FSHD pathology is caused by the misexpression and missplicing of the DUX4 (double homeobox 4) gene, encoded within the repeat array, resulting in production of a pathogenic protein, DUX4-FL. We have analyzed DUX4 mRNA and protein expression in a large collection of myogenic cells and muscle biopsies derived from muscles of FSHD1 affected subjects and their unaffected first-degree relatives. We confirmed that stable DUX4-fl mRNA and protein were expressed in myogenic cells and muscle tissues derived from FSHD affected subjects, including several genetically diagnosed adults yet to show clinical manifestations of the disease; however, there was great individual and familial variation in the levels of DUX4-FL. In addition, we found DUX4-fl mRNA and protein expression in muscle biopsies and myogenic cells from genetically unaffected relatives of the FSHD subjects, although at a significantly lower frequency. These results establish that DUX4-fl expression per se is not sufficient for FSHD muscle pathology. To investigate if subtle differences in the epigenetic status of the 4q35 region could account for the wide variation in DUX4-fl expression among FSHD1 subjects and potentially the spurious expression in certain unaffected controls, family cohorts of myogenic cells from FSHD1 subjects were tested for their sensitivity to small molecules that can alter the chromatin state. We find that myogenic cells from FSHD1 subjects are overall epigenetically poised to express DUX4 compared with unaffected subjects; however, FSHD1 subjects show individual differences in their capacity to express DUX4-fl in response to DNA demethylation and blocking histone deacetylation. Therefor, individual differences in the epigenetic status likely impacts progression of disease pathology, variability in age of onset, disease severity, and asymmetry of affected muscles

    Online co-design of a university Work-Based Learning degree programme: lessons learned from comparing cases in United Kingdom and Eswatini

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    Greater collaboration is required between universities, industry and society to provide the engineering education that will tackle society’s challenges. Work-based learning (WBL) programmes offer an industry-aligned, academically-informed education to support such socio-economic development. Co-design of such programmes is vital with responses to the COVID-19 pandemic innovating alternative ways to design programmes. Knowles et al (2021) [1] outlined an approach to online programme co-design in the UK university context, framed using Signature Pedagogy and through online conferencing and Miro (online whiteboard). Subsequently, the approach has been utilised to co-design a WBL degree programme in Electrical Engineering in Eswatini, supported by Knowles and other UK and Eswatini colleagues. This paper compares and contrasts cases from UK and Eswatini, and from this address the research question, “What considerations are required to support an effective online process to co-design a work-based learning programme in Engineering?” A collaborative autoethnographic methodology based around field notes, observations and reflections is used to allow exploration across pedagogy, technology, work practices, expectations and challenges. Many aspects of the approach worked well in both cases (for example, effectiveness of Signature Pedagogy, Miro as shared space), whereas differences arose related to limitations in the synchronous use of technologies, and readiness to adopt an outcome-focused approach. Addressing these differences, along with balancing progress against full participation and having clear expectations of participants, are key considerations in online co-design of WBL programmes. Moreover, the approach of Knowles (ibid) has shown to be adaptable with potential for broader adoption

    Methylated DNA recognition during the reversal of epigenetic silencing is regulated by cysteine and cerine residues in the Epstein-Barr Virus lytic switch protein

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    Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with various malignancies, including Burkitt's lymphoma and nasopharyngeal carcinoma. Like all herpesviruses, the EBV life cycle alternates between latency and lytic replication. During latency, the viral genome is largely silenced by host-driven methylation of CpG motifs and, in the switch to the lytic cycle, this epigenetic silencing is overturned. A key event is the activation of the viral BRLF1 gene by the immediate-early protein Zta. Zta is a bZIP transcription factor that preferentially binds to specific response elements (ZREs) in the BRLF1 promoter (Rp) when these elements are methylated. Zta's ability to trigger lytic cycle activation is severely compromised when a cysteine residue in its bZIP domain is mutated to serine (C189S), but the molecular basis for this effect is unknown. Here we show that the C189S mutant is defective for activating Rp in a Burkitt's lymphoma cell line. The mutant is compromised both in vitro and in vivo for binding two methylated ZREs in Rp (ZRE2 and ZRE3), although the effect is striking only for ZRE3. Molecular modeling of Zta bound to methylated ZRE3, together with biochemical data, indicate that C189 directly contacts one of the two methyl cytosines within a specific CpG motif. The motif's second methyl cytosine (on the complementary DNA strand) is predicted to contact S186, a residue known to regulate methyl-ZRE recognition. Our results suggest that C189 regulates the enhanced interaction of Zta with methylated DNA in overturning the epigenetic control of viral latency. As C189 is conserved in many bZIP proteins, the selectivity of Zta for methylated DNA may be a paradigm for a more general phenomenon

    Dynamic shapes of the zygote and two-cell mouse and human

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    Mouse zygote morphokinetics were measured during interphase, the mitotic period, cytokinesis, and two-cell stage. Sequences of rounder–distorted–rounder shapes were revealed, as were changing patterns of cross section area. A calcium chelator and an actin-disrupting agent inhibited the area changes that occurred between pronuclear envelope breakdown and cytokinesis. During cell division, two vortices developed in each nascent cell and they rotated in opposite directions at each end of the cell, a pattern that sometimes persisted for up to 10 h. Exchange with the environment may have been promoted by these shape and area cycles and persisting circulation in the cytoplasm may have a similar function between a cell's interior and periphery. Some of these movements were sporadically also seen in human zygotes with abnormal numbers of pronuclei and the two-cell stages that developed from these compromised human zygotes

    Discrete mode laser diodes with very narrow linewidth emission

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    Ex-facet, free-running low linewidth (~100 kHz), single mode laser emission is demonstrated using low cost, regrowth-free ridge waveguide Discrete Mode Fabry PĂ©rot laser diode chips. These narrow linewidths are obtained from sub mW emission powers and above
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