100 research outputs found

    Navigating an academic maze: experiences of an international female scholar

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    Academia is a world filled with bright people searching for explanations for phenomena around us, and developing and testing new theories to explain the hows and whys of our experience. It is a world defined by a drive to expand the boundaries of knowledge, and is ostensibly characterized by intellectual enlightenment and relentless progress. But is academia truly progressive? Perhaps for some of us. For others, however, it is still a world where many people struggle to be seen, to be heard, and to succeed—especially if you are in the minority (e.g., you are female, international, a person of color, or have other features that put you in a minority category). In this essay, I share some of my personal experiences as an international female academic, with the hope that my challenges—and the ways I work to overcome them—will resonate with other people in the margins of our presumably progressive field

    How nascent occupations construct a mandate: the case of service designers' ethos

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    In this paper, we study the way that nascent occupations constructing an occupational mandate invoke not only skills and expertise or a new technology to distinguish themselves from other occupations, but also their values. We studied service design, an emerging occupation whose practitioners aim to understand customers and help organizations develop new or improved services and customer experiences, translate those into feasible solutions, and implement them. Practitioners enacted their values in their daily work activities through a set of material practices, such as shadowing customers or front-line staff, conducting interviews in the service context, or creating “journey maps” of a service user’s experience. The role of values in the construction of an occupational mandate is particularly salient for occupations such as service design, which cannot solely rely on skills and technical expertise as sources of differentiation. We show how service designers differentiated themselves from other competing occupations by highlighting how their values make their work practices unique. Both values and work practices, what service designers call their ethos, were essential to enable service designers to define the proper conduct and modes of thinking characteristic of their occupational mandate

    Downregulation of miR-99a/let-7c/miR-125b miRNA cluster predicts clinical outcome in patients with unresected malignant pleural mesothelioma

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    Malignant pleural mesothelioma (MPM) is an aggressive tumor with a dismal overall survival (OS) and to date no molecular markers are available to guide patient management. This study aimed to identify a prognostic miRNA signature in MPM patients who did not undergo tumor resection. Whole miRNA profiling using a microarray platform was performed using biopsies on 27 unresected MPM patients with distinct clinical outcome: 15 patients had short survival (OS < 12 months) and 12 patients had long survival (OS > 36 months). Three prognostic miRNAs (mir- 99a, let-7c, and miR-125b) encoded at the same cluster (21q21) were selected for further validation and tested on publicly available miRNA sequencing data from 72 MPM patients with survival data. A risk model was built based on these 3 miRNAs that was validated by quantitative PCR in an independent set of 30 MPM patients. High-risk patients had shorter median OS (7.6 months) as compared with low-risk patients (median not reached). In the multivariate Cox model, a high-risk score was independently associated with shorter OS (HR=3.14; 95% CI, 1.18-8.34; P=0.022). Our study identified that the downregulation of the miR-99a/let-7/miR-125b miRNA cluster predicts poor outcome in unresected MPM

    Agronomic performance and transcriptional analysis of carotenoid biosynthesis in fruits of transgenic HighCaro and control tomato lines under field conditions

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    Genetic manipulation of carotenoid biosynthesis in higher plants has been the objective of a number of biotechnology programs, e.g. the Golden Rice Program. However, tomato (Solanumlycopersicum L.), which naturally accumulates lycopene in fruits, has attracted the attention of many groups who have manipulated it to increase or diversify carotenoid accumulation. One of the most significant achievements was “HighCaro (HC),” a transgenic tomato plant constitutively expressing the tomato lycopene beta-cyclase (tLcy-b), that produces orange fruits due to the complete conversion of lycopene to β-carotene. In this article we report the results of a field trial conducted in Metaponto (Italy) on HC and on two control genotypes to evaluate the stability of the transgenic trait and their yield performances. Transcriptional regulation of eight genes involved in carotenogenesis was assayed by quantitative real-time PCR (qRT-PCR) analysis on fruits collected at four distinct development stages. Statistical analysis results demonstrated that in field conditions the transgene maintained its ability to induce the conversion of lycopene to β-carotene. Moreover, agronomic performances and fruit quality in the transgenic line were not impaired by this metabolic disturbance. Results of qRT-PCR analysis suggested that transcription of PSY-1, PDS and ZDS genes were developmentally regulated in both genotypes. Unexpectedly, Lcy-b expression in transgenic fruits was also developmentally regulated, despite the fact that the gene was driven by a constitutive promoter. Our data provide evidence that in photosynthetic cells a strict and aspecific mechanism controls the level of transcripts until the onset of chromoplasts differentiation, at which point a gene-specific control on transcription takes place

    Managing by design

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    This editorial written by myself and Marc Gruber of EPFL. It explores the role of design thinking in the management of large organisations, and focuses on how design principles can be applied to the design of the workplace and the nature of work itself. As Head of Service Design at the RCA, my contribution is on how to apply design thinking methods for managers and the 6 key elements described in this approach In the last decade the importance of design and the value of design thinking as a tool for innovation has been recognized by both business and government. Design has become a strategic tool for business helping to translate technological innovation into user value, connecting with consumer needs and creating compelling product and service experiences that create new business value. In this paper we consider a further application of design thinking by considering how managers can apply it to the design of the workplace experience. Many enterprises, especially those in the knowledge economy, are defined by their human resources and their capacity to attract and retain talent. In this competitive environment the design of the employee experience and the services that support them and enable them to deliver value to the clients and colleagues, is a key differentiator. Applying design thinking to the design of work itself, the systems that support it, and the physical and virtual environments in which it takes place can help business and organizational leaders to attract and retain top talent, as well as to enhance productivity and operational effectiveness. In this paper we explore the key factors and principles by which leaders and managers can apply design thinking to transform the workplace experience and we propose 6 key elements for managers to enable that transformation and enhance social capital and business and organisational performance

    Depolarization-Evoked Secretion Requires Two Vicinal Transmembrane Cysteines of Syntaxin 1A

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    BACKGROUND: The interactions of the voltage-gated Ca(2+) channel (VGCC) with syntaxin 1A (Sx 1A), Synaptosome-associated protein of 25 kD (SNAP-25), and synaptotagmin, couple electrical excitation to evoked secretion. Two vicinal Cys residues, Cys 271 and Cys 272 in the Sx 1A transmembrane domain, are highly conserved and participate in modulating channel kinetics. Each of the Sx1A Cys mutants, differently modify the kinetics of Cav1.2, and neuronal Cav2.2 calcium channel. METHODOLOGY/PRINCIPLE FINDINGS: We examined the effects of various Sx1A Cys mutants and the syntaxin isoforms 2, 3, and 4 each of which lack vicinal Cys residues, on evoked secretion, monitoring capacitance transients in a functional release assay. Membrane capacitance in Xenopus oocytes co-expressing Cav1.2, Sx1A, SNAP-25 and synaptotagmin, which is Bot C- and Bot A-sensitive, was elicited by a double 500 ms depolarizing pulse to 0 mV. The evoked-release was obliterated when a single Cys Sx1A mutant or either one of the Sx isoforms were substituted for Sx 1A, demonstrating the essential role of vicinal Cys residues in the depolarization mediated process. Protein expression and confocal imaging established the level of the mutated proteins in the cell and their targeting to the plasma membrane. CONCLUSIONS/SIGNIFICANCE: We propose a model whereby the two adjacent transmembranal Cys residues of Sx 1A, lash two calcium channels. Consistent with the necessity of a minimal fusion complex termed the excitosome, each Sx1A is in a complex with SNAP-25, Syt1, and the Ca(2+) channel. A Hill coefficient >2 imply that at least three excitosome complexes are required for generating a secreting hetero-oligomer protein complex. This working model suggests that a fusion pore that opens during membrane depolarization could be lined by alternating transmembrane segments of Sx1A and VGCC. The functional coupling of distinct amino acids of Sx 1A with VGCC appears to be essential for depolarization-evoked secretion

    Let’s not forget tautomers

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    A compound exhibits tautomerism if it can be represented by two structures that are related by an intramolecular movement of hydrogen from one atom to another. The different tautomers of a molecule usually have different molecular fingerprints, hydrophobicities and pKa’s as well as different 3D shape and electrostatic properties; additionally, proteins frequently preferentially bind a tautomer that is present in low abundance in water. As a result, the proper treatment of molecules that can tautomerize, ~25% of a database, is a challenge for every aspect of computer-aided molecular design. Library design that focuses on molecular similarity or diversity might inadvertently include similar molecules that happen to be encoded as different tautomers. Physical property measurements might not establish the properties of individual tautomers with the result that algorithms based on these measurements may be less accurate for molecules that can tautomerize—this problem influences the accuracy of filtering for library design and also traditional QSAR. Any 2D or 3D QSAR analysis must involve the decision of if or how to adjust the observed Ki or IC50 for the tautomerization equilibria. QSARs and recursive partitioning methods also involve the decision as to which tautomer(s) to use to calculate the molecular descriptors. Docking virtual screening must involve the decision as to which tautomers to include in the docking and how to account for tautomerization in the scoring. All of these decisions are more difficult because there is no extensive database of measured tautomeric ratios in both water and non-aqueous solvents and there is no consensus as to the best computational method to calculate tautomeric ratios in different environments
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