543 research outputs found
Modern Management: Concepts and Skills -12/E.
Managers of today continue to face new opportunities and challenges. These opportunities include much publicized task like Florida’s University Studios opening a new Harry Potter attraction and Apple encouraging technology innovation beyond the iPad and the iPhone. At the same time, other companies face intense challenges, such as BP’s task of cleaning up an oil well leak in the Gulf of Mexico. Perhaps because these opportunities and challenges are so daunting, managers today arguably have the ability to earn higher financial reward than at any other time in history.
This 12th edition of the Modern Management Learning Package, this text plus its ancillaries, continues the recognized and distinctive tradition in management education that has extended more than 30 years. As in previous edition, this current edition of the Modern Management Learning Package has focused on a single objective: maximizing student learning of critical management concept. All revisions reflect instructor and student feedback regarding ways to refashion the package to further enhance student learning. Starting with the text, the following section explain each major component of this revision
NRAGE associates with the anti-apoptotic factor Che-1 and regulates its degradation to induce cell death
Neurotrophin receptor-interacting MAGE homolog (NRAGE) has been recently identified as a cell-death inducer, involved in molecular events driving cells through apoptotic networks during neuronal development. Recently, we have focused on the functional role of Che-1, also known as apoptosis-antagonizing transcription factor (AATF), a protein involved in cell cycle control and gene transcription. Increasing evidence suggests that Che-1 is involved in apoptotic signalling in neural tissues. In cortical neurons Che-1 exhibits an anti-apoptotic activity, protecting cells from neuronal damage induced by amyloid β-peptide. Here, we report that Che-1 interacts with NRAGE and that an EGFP-NRAGE fusion protein inhibits nuclear localization of Che-1, by sequestering it within the cytoplasmic compartment. Furthermore, NRAGE overexpression downregulates endogenous Che-1 by targeting it for proteasome-dependent degradation. Finally, we propose that Che-1 is a functional antagonist of NRAGE, because its overexpression completely reverts NRAGE-induced cell-death
Early-stage Fundraising of University Spin-offs: A Study through Demand-site Perspectives
University spin-offs have increasingly received attention from academia, governments and policy-makers. However, there are only a limited number of studies which fully understand the contribution made by the founding team to fundraising, specifically how they use their social networks and capabilities, especially within the university spin-off context. Employing a resource-based view theory and social networks approach, this paper examines whether a founding team exploits its social networks and capabilities to signal the value of a university spin-off. Capabilities are analysed through a set of constructs - technology, strategy, human capital, organizational viability and commercial resource - that have been derived from previous literature. The contribution made by social networks is evaluated using three dimensions - structure, governance and content - which form the construct of relationships within a network. Based on data from 181 university spin-offs in Spain, this paper empirically demonstrates that by exploiting social networks a founding team can improve its capabilities which, in turn, enhance its fundraising ability
Peptide Ligands for Pro-survival Protein Bfl-1 from Computationally Guided Library Screening
Pro-survival members of the Bcl-2 protein family inhibit cell death by binding short helical BH3 motifs in pro-apoptotic proteins. Mammalian pro-survival proteins Bcl-x[subscript L], Bcl-2, Bcl-w, Mcl-1, and Bfl-1 bind with varying affinities and specificities to native BH3 motifs, engineered peptides, and small molecules. Biophysical studies have determined interaction patterns for these proteins, particularly for the most-studied family members Bcl-x[subscript L] and Mcl-1. Bfl-1 is a pro-survival protein implicated in preventing apoptosis in leukemia, lymphoma, and melanoma. Although Bfl-1 is a promising therapeutic target, relatively little is known about its binding preferences. We explored the binding of Bfl-1 to BH3-like peptides by screening a peptide library that was designed to sample a high degree of relevant sequence diversity. Screening using yeast-surface display led to several novel high-affinity Bfl-1 binders and to thousands of putative binders identified through deep sequencing. Further screening for specificity led to identification of a peptide that bound to Bfl-1 with K[subscript d] < 1 nM and very slow dissociation from Bfl-1 compared to other pro-survival Bcl-2 family members. A point mutation in this sequence gave a peptide with ~50 nM affinity for Bfl-1 that was selective for Bfl-1 in equilibrium binding assays. Analysis of engineered Bfl-1 binders deepens our understanding of how the binding profiles of pro-survival proteins differ and may guide the development of targeted Bfl-1 inhibitors.National Institute of General Medical Sciences (U.S.) (Award GM084181)National Institute of General Medical Sciences (U.S.) (Award P50-GM68762
Recommended from our members
CORPORATE GOVERNANCE AND INVESTORS' PERCEPTIONS OF FOREIGN IPO VALUE: AN INSTITUTIONAL PERSPECTIVE
We build on sociology-grounded research on financial market behavior and suggest a “nested” legitimacy framework to explore U.S. investor perceptions of foreign IPO value. We draw on a fuzzy-set theoretic approach to demonstrate how different combinations of monitoring and incentive-based corporate governance mechanisms lead to the same level of investor valuations of firms. We also argue that institutional factors related to the minority shareholder protection strength in the foreign IPO’s home country represent a boundary condition that affects the number of governance mechanisms required to achieve U.S. investors’ high value perceptions. Our findings, drawn from a unique, hand-collected dataset of foreign IPOs in the U.S, contribute to the sociological perspective on comparative corporate governance and the inter-dependencies between organizations and institutions
Bcl-2 inhibits apoptosis by increasing the time-to-death and intrinsic cell-to-cell variations in the mitochondrial pathway of cell death
BH3 mimetics have been proposed as new anticancer therapeutics. They target
anti-apoptotic Bcl-2 proteins, up-regulation of which has been implicated in
the resistance of many cancer cells, particularly leukemia and lymphoma cells,
to apoptosis. Using probabilistic computational modeling of the mitochondrial
pathway of apoptosis, verified by single-cell experimental observations, we
develop a model of Bcl-2 inhibition of apoptosis. Our results clarify how Bcl-2
imparts its anti-apoptotic role by increasing the time-to-death and
cell-to-cell variability. We also show that although the commitment to death is
highly impacted by differences in protein levels at the time of stimulation,
inherent stochastic fluctuations in apoptotic signaling are sufficient to
induce cell-to-cell variability and to allow single cells to escape death. This
study suggests that intrinsic cell-to-cell stochastic variability in apoptotic
signaling is sufficient to cause fractional killing of cancer cells after
exposure to BH3 mimetics. This is an unanticipated facet of cancer
chemoresistance.Comment: 11 pages, In pres
A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection
There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways; in this study we took advantage of the SeeSaw Reporter, in which the repair of double-strand breaks by homology-independent or -dependent mechanisms is distinguished by the accumulation of green or red fluorescence, respectively. Using a genome-wide human esiRNA (endoribonuclease- prepared siRNA) library, we isolate genes that control the recombination/endjoining ratio. Here we report that two distinct sets of genes are involved in the control of the balance between NHEJ and HR: those that are required to facilitate recombination and those that favour NHEJ. This last category includes CCAR2/DBC1, which we show inhibits recombination by limiting the initiation and the extent of DNA end resection, thereby acting as an antagonist of CtIP
- …