347 research outputs found

    The CEO Effect: A Longitudinal, Multi-Level Analysis of the Relationship Between Executive Orientation and Corporate Social Strategy

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    Corporate social responsibility (CSR) is a strategic issue. Yet, research in this area has primarily focused on establishing a link between CSR and financial performance, with significantly less attention given to the antecedents of CSR at the individual, firm or industry levels. Notably, despite popular anecdotal examples that link the personal values, beliefs or characteristics of business leaders to the socially responsible nature of their companies, very little is actually known empirically about the relationship between executive orientation and the corporate social strategy pursued by the firm. The empirical research study presented in this dissertation is designed to fill this important gap. First, I synthesize the vast literature in the general CSR domain into a new typology of corporate social strategy (CSS) that distinguishes a firm’s approach to CSR along its breadth and depth dimensions. Then, using an upper echelon framework based in the strategic choice and strategic decision-making literatures, I examine the relationship between executive orientation and variances observed in firm responses to social and environmental issues over time. I argue specifically that an open executive orientation, as reflected in a CEO’s worldview, and variables such as functional background, educational specialization and international experience affect the selective perception, interpretation and therefore choice of the breadth and depth of a firm’s CSS. Furthermore, institutional theory is used to argue that the level of managerial discretion at the industry level as well as general industry norms will attenuate theses relationships. In so doing, I develop a longitudinal, multi-level, mixed determinant model of the relationship between executive orientation and CSS. Random coefficient modeling (RCM) is then used to test the CEO effect on CSS over time, by modeling the individual CSS growth trajectories of 349 firms from 1991-2009 using HLM6 software. With 19 years of data, over 1,000 CEOs and 6,334 firm-year observations, this thesis represents the first longitudinal study to explicitly model the rate of adoption of aggregate corporate social strategy (ACSS), breadth of corporate social strategy (BCSS) and depth of corporate social strategy (DCSS) over the last two decades. This analysis yielded three important results at the CEO, firm and industry levels. First, the CEO effect on CSS ranges between 3-14% and evidence supports that some aspects of an open executive orientation are indeed important determinants of initial levels and rates of adoption of CSS over time. The findings also reveal that the overall level of CSS has not grown substantively over the last two decades, with most firms in 2009 still engaging in a Derivative (shallow/narrow) CSS. Furthermore, unlike previous studies that confound negative and positive CSR, this dissertation demonstrates that industry membership is not an important determinant of the strategic choice of positive CSS, nor are institutional pressures moderating factors in the executive orientation – CSS relationship. This thesis thus makes significant theoretical and methodological contributions to research in the upper echelons, CSR and institutional theory domains, as well as has important implications for practice

    Statistical Mechanics of Allosteric Enzymes

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    The concept of allostery in which macromolecules switch between two different conformations is a central theme in biological processes ranging from gene regulation to cell signaling to enzymology. Allosteric enzymes pervade metabolic processes, yet a simple and unified treatment of the effects of allostery in enzymes has been lacking. In this work, we take a step toward this goal by modeling allosteric enzymes and their interaction with two key molecular players—allosteric regulators and competitive inhibitors. We then apply this model to characterize existing data on enzyme activity, comment on how enzyme parameters (such as substrate binding affinity) can be experimentally tuned, and make novel predictions on how to control phenomena such as substrate inhibition

    Quantitative biology: where modern biology meets physical sciences

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    Quantitative methods and approaches have been playing an increasingly important role in cell biology in recent years. They involve making accurate measurements to test a predefined hypothesis in order to compare experimental data with predictions generated by theoretical models, an approach that has benefited physicists for decades. Building quantitative models in experimental biology not only has led to discoveries of counterintuitive phenomena but has also opened up novel research directions. To make the biological sciences more quantitative, we believe a two-pronged approach needs to be taken. First, graduate training needs to be revamped to ensure biology students are adequately trained in physical and mathematical sciences and vice versa. Second, students of both the biological and the physical sciences need to be provided adequate opportunities for hands-on engagement with the methods and approaches necessary to be able to work at the intersection of the biological and physical sciences. We present the annual Physiology Course organized at the Marine Biological Laboratory (Woods Hole, MA) as a case study for a hands-on training program that gives young scientists the opportunity not only to acquire the tools of quantitative biology but also to develop the necessary thought processes that will enable them to bridge the gap between these disciplines

    Artifact‐Free Quantification and Sequencing of Rare Recombinant Viruses by Using Drop‐Based Microfluidics

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    Recombination is an important driver in the evolution of viruses and thus is key to understanding viral epidemics and improving strategies to prevent future outbreaks. Characterization of rare recombinant subpopulations remains technically challenging because of artifacts such as artificial recombinants, known as chimeras, and amplification bias. To overcome this, we have developed a high‐throughput microfluidic technique with a second verification step in order to amplify and sequence single recombinant viruses with high fidelity in picoliter drops. We obtained the first artifact‐free estimate of in vitro recombination rate between murine norovirus strains MNV‐1 and WU20 co‐infecting a cell (Prec=3.3×10−4±2×10−5) for a 1205 nt region. Our approach represents a time‐ and cost‐effective improvement over current methods, and can be adapted for genomic studies requiring artifact‐ and bias‐free selective amplification, such as microbial pathogens, or rare cancer cells.Artifact‐free RNA amplification: single viral RNA templates produced from a co‐infected culture are encapsulated into picoliter drops with a one‐step RT‐PCR cocktail. A fluorescent dye in the cocktail identifies drops containing potential recombinant amplicons, which are sorted based on fluorescence, followed by Sanger sequencing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116006/1/cbic201500384.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/116006/2/cbic201500384-sup-0001-misc_information.pd

    Transcriptional Basis of Mouse and Human Dendritic Cell Heterogeneity

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    Dendritic cells (DCs) play a critical role in orchestrating adaptive immune responses due to their unique ability to initiate T cell responses and direct their differentiation into effector lineages. Classical DCs have been divided into two subsets, cDC1 and cDC2, based on phenotypic markers and their distinct abilities to prime CD8 and CD4 T cells. While the transcriptional regulation of the cDC1 subset has been well characterized, cDC2 development and function remain poorly understood. By combining transcriptional and chromatin analyses with genetic reporter expression, we identified two principal cDC2 lineages defined by distinct developmental pathways and transcriptional regulators, including T-bet and RORgt, two key transcription factors known to define innate and adaptive lymphocyte subsets. These novel cDC2 lineages were characterized by distinct metabolic and functional programs. Extending our findings to humans revealed conserved DC heterogeneity and the presence of the newly defined cDC2 subsets in human cancer

    Are your students safe to learn? The role of lecturer’s authentic leadership in the creation of psychologically safe environments and their impact on academic performance:The role of teacher's authentic leadership on the creation of psychologically safe environments and their impact on academic performance

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    As the role of students and lecturers in higher education changes, several questions emerge about the role of each of them on students? academic performance. This includes questions regarding the impact of the relationships between students, lecturer?s characteristics and the social environment on students? performance. To address these questions, this article reports a study of the impact of lecturer authentic leadership, psychological safety and network density on academic performance. It explores the relationship between network density, psychological safety and lecturer authentic leadership. A questionnaire was distributed to undergraduate students. A positive impact of lecturer authentic leadership and psychological safety on academic performance was found. Students from high-density groups tended to show better academic performance, higher psychological safety and tended to see their lecturers as being more authentic. A reflection on the role of the lecturer in higher education settings is presented. It also presents some recommendations on how student academic performance can be improved by the adoption of specific behaviours by their lecturer

    Molecular Fingerprint and Developmental Regulation of the Tegmental GABAergic and Glutamatergic Neurons Derived from the Anterior Hindbrain

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    Tegmental nuclei in the ventral midbrain and anterior hindbrain control motivated behavior, mood, memory, and movement. These nuclei contain inhibitory GABAergic and excitatory glutamatergic neurons, whose molecular diversity and development remain largely unraveled. Many tegmental neurons originate in the embryonic ventral rhombomere 1 (r1), where GABAergic fate is regulated by the transcription factor (TF) Tal1. We used single-cell mRNA sequencing of the mouse ventral r1 to characterize the Tal1-dependent and independent neuronal precursors. We describe gene expression dynamics during bifurcation of the GABAergic and glutamatergic lineages and show how active Notch signaling promotes GABAergic fate selection in postmitotic precursors. We identify GABAergic precursor subtypes that give rise to distinct tegmental nuclei and demonstrate that Sox14 and Zfpm2, two TFs downstream of Tal1, are necessary for the differentiation of specific tegmental GABAergic neurons. Our results provide a framework for understanding the development of cellular diversity in the tegmental nuclei.Peer reviewe

    A Method for Detecting Circulating Tumor Cells Based on the Measurement of Single-Cell Metabolism in Droplet-Based Microfluidics

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    The number of circulating tumor cells (CTCs) in blood is strongly correlated with the progress of metastatic cancer. Current methods to detect CTCs are based on immunostaining or discrimination of physical properties. Herein, a label-free method is presented exploiting the abnormal metabolic behavior of cancer cells. A single-cell analysis technique is used to measure the secretion of acid from individual living tumor cells compartmentalized in microfluidically prepared, monodisperse, picoliter (pL) droplets. As few as 10 tumor cells can be detected in a background of 200 000 white blood cells and proof-of-concept data is shown on the detection of CTCs in the blood of metastatic patients

    Single-Cell Transcriptional Profiling Reveals Signatures of Helper, Effector, and Regulatory MAIT Cells during Homeostasis and Activation

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    Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that recognize microbial vitamin B metabolites and have emerging roles in infectious disease, autoimmunity, and cancer. Although MAIT cells are identified by a semi-invariant TCR, their phenotypic and functional heterogeneity is not well understood. Here we present an integrated single cell transcriptomic analysis of over 76,000 human MAIT cells during early and prolonged Ag-specific activation with the MR1 ligand 5-OP-RU and nonspecific TCR stimulation. We show that MAIT cells span a broad range of homeostatic, effector, helper, tissue-infiltrating, regulatory, and exhausted phenotypes, with distinct gene expression programs associated with CD4+ or CD8+ coexpression. During early activation, MAIT cells rapidly adopt a cytotoxic phenotype characterized by high expression of GZMB, IFNG and TNF In contrast, prolonged stimulation induces heterogeneous states defined by proliferation, cytotoxicity, immune modulation, and exhaustion. We further demonstrate a FOXP3 expressing MAIT cell subset that phenotypically resembles conventional regulatory T cells. Moreover, scRNAseq-defined MAIT cell subpopulations were also detected in individuals recently exposed to Mycobacterium tuberculosis, confirming their presence during human infection. To our knowledge, our study provides the first comprehensive atlas of human MAIT cells in activation conditions and defines substantial functional heterogeneity, suggesting complex roles in health and disease
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