Taking a “Deep Dive”: What Only a Top Leader Can Do

Unlike most historical accounts of strategic change inside large firms, empirical research on strategic management rarely uses the day-to-day behaviors of top executives as the unit of analysis. By examining the resource allocation process closely, we introduce the concept of a deep dive, an intervention when top management seizes hold of the substantive content of a strategic initiative and its operational implementation at the project level, as a way to drive new behaviors that enable an organization to shift its performance trajectory into new dimensions unreachable with any of the previously described forms of intervention. We illustrate the power of this previously underexplored change mechanism with a case study, in which a well-established firm overcame barriers to change that were manifest in a wide range of organizational routines and behavioral norms that had been fostered by the pre-existing structural context of the firm.Strategic Change, Resource Allocation Process, Top-down Intervention

Transport of Molecular Motor Dimers in Burnt-Bridge Models

Dynamics of molecular motor dimers, consisting of rigidly bound particles that move along two parallel lattices and interact with underlying molecular tracks, is investigated theoretically by analyzing discrete-state stochastic continuous-time burnt-bridge models. In these models the motion of molecular motors is viewed as a random walk along the lattices with periodically distributed weak links (bridges). When the particle crosses the weak link it can be destroyed with a probability $p$, driving the molecular motor motion in one direction. Dynamic properties and effective generated forces of dimer molecular motors are calculated exactly as a function of a concentration of bridges $c$ and burning probability $p$ and compared with properties of the monomer motors. It is found that the ratio of the velocities of the dimer and the monomer can never exceed 2, while the dispersions of the dimer and the monomer are not very different. The relative effective generated force of the dimer (as compared to the monomer) also cannot be larger than 2 for most sets of parameters. However, a very large force can be produced by the dimer in the special case of $c=1/2$ for non-zero shift between the lattices. Our calculations do not show the significant increase in the force generated by collagenase motor proteins in real biological systems as predicted by previous computational studies. The observed behavior of dimer molecular motors is discussed by considering in detail the particle dynamics near burnt bridges.Comment: 21 pages and 11 figure

Comparative Effectiveness Research, COURAGE, and Technological Abandonment

When a major study finds that a widely used medical treatment is no better than a less expensive alternative, do physicians stop using it? Policymakers hope that comparative effectiveness research will identify less expensive substitutes for widely-used treatments, but physicians may be reluctant to abandon profitable therapies. We examine the impact of the COURAGE trial, which found that medical therapy is as effective as percutaneous coronary intervention (PCI) for patients with stable angina, on practice patterns. Using hospital discharge data from US community, Veterans Administration, and English hospitals, we detect a moderate decline in PCI volume post-COURAGE. However, many patients with stable angina continue to receive PCI. We do not find differences in PCI volume trends by reimbursement scheme or hospitals’ teaching status, ownership, or degree of vertical integration.

Dynamic Properties of Molecular Motors in Burnt-Bridge Models

Dynamic properties of molecular motors that fuel their motion by actively interacting with underlying molecular tracks are studied theoretically via discrete-state stochastic ``burnt-bridge'' models. The transport of the particles is viewed as an effective diffusion along one-dimensional lattices with periodically distributed weak links. When an unbiased random walker passes the weak link it can be destroyed (``burned'') with probability p, providing a bias in the motion of the molecular motor. A new theoretical approach that allows one to calculate exactly all dynamic properties of motor proteins, such as velocity and dispersion, at general conditions is presented. It is found that dispersion is a decreasing function of the concentration of bridges, while the dependence of dispersion on the burning probability is more complex. Our calculations also show a gap in dispersion for very low concentrations of weak links which indicates a dynamic phase transition between unbiased and biased diffusion regimes. Theoretical findings are supported by Monte Carlo computer simulations.Comment: 14 pages. Submitted to J. Stat. Mec

Fine‐needle aspiration cytology of metastatic spindle cell follicular thyroid carcinoma: A case report

Follicular thyroid carcinoma, spindle cell variant is extremely rare. The tumor is predominantly composed of spindle cells with a fusiform appearance that are arranged in intersecting fascicles. Fine‐needle aspiration biopsy of this entity has not been previously described. We report a case of a 58‐year‐old woman who presented with metastasis to a left neck lymph node 15 years after the original diagnosis. Fine‐needle aspiration cytology showed numerous bland, spindled to epithelioid cells with thin, elongated, and plump nuclei with finely granular chromatin and inconspicuous nucleoli. The tumor cells had a moderate amount of cytoplasm with occasional elongated cytoplasmic tails. The cells were arranged in irregular aggregates with a fascicular pattern or singly dispersed. The tumor cells demonstrated positive staining for pan‐keratin, PAX8, thyroid transcription factor‐1, and thyroglobulin, which confirmed thyroid primary origin

Three-Loop Radiative-Recoil Corrections to Hyperfine Splitting in Muonium

We calculate three-loop radiative-recoil corrections to hyperfine splitting in muonium generated by the diagrams with the first order electron and muon polarization loop insertions in graphs with two exchanged photons. These corrections are enhanced by the large logarithm of the electron-muon mass ratio. The leading logarithm squared contribution was obtained a long time ago. Here we calculate the single-logarithmic and nonlogarithmic contributions. We previously calculated the three-loop radiative-recoil corrections generated by two-loop polarization insertions in the exchanged photons. The current paper therefore concludes calculation of all three-loop radiative-recoil corrections to hyperfine splitting in muonium generated by diagrams with closed fermion loop insertions in the exchanged photons. The new results obtained here improve the theory of hyperfine splitting, and affect the value of the electron-muon mass ratio extracted from experimental data on the muonium hyperfine splitting.Comment: 27 pages, 6 figures, 7 table

Seeing double with K2: Testing re-inflation with two remarkably similar planets around red giant branch stars

Despite more than 20 years since the discovery of the first gas giant planet with an anomalously large radius, the mechanism for planet inflation remains unknown. Here, we report the discovery of EPIC228754001.01, an inflated gas giant planet found with the NASA K2 Mission, and a revised mass for another inflated planet, K2-97b. These planets reside on ~9 day orbits around host stars which recently evolved into red giants. We constrain the irradiation history of these planets using models constrained by asteroseismology and Keck/HIRES spectroscopy and radial velocity measurements. We measure planet radii of 1.31 +\- 0.11 Rjup and and 1.30 +\- 0.07 Rjup, respectively. These radii are typical for planets receiving the current irradiation, but not the former, zero age main sequence irradiation of these planets. This suggests that the current sizes of these planets are directly correlated to their current irradiation. Our precise constraints of the masses and radii of the stars and planets in these systems allow us to constrain the planetary heating efficiency of both systems as 0.03% +0.03%/-0.02%. These results are consistent with a planet re-inflation scenario, but suggest the efficiency of planet re-inflation may be lower than previously theorized. Finally, we discuss the agreement within 10% of stellar masses and radii, and planet masses, radii, and orbital periods of both systems and speculate that this may be due to selection bias in searching for planets around evolved stars.Comment: 18 pages, 15 figures, accepted to AJ. Figures 11, 12, and 13 are the key figures of the pape

ARC (NSC 188491) has identical activity to Sangivamycin (NSC 65346) including inhibition of both P-TEFb and PKC

<p>Abstract</p> <p>Background</p> <p>The nucleoside analog, ARC (NSC 188491) is a recently characterized transcriptional inhibitor that selectively kills cancer cells and has the ability to perturb angiogenesis <it>in vitro</it>. In this study, the mechanism of action of ARC was further investigated by comparing <it>in vitro </it>and <it>in vivo </it>activity with other anti-neoplastic purines.</p> <p>Methods</p> <p>Structure-based homology searches were used to identify those compounds with similarity to ARC. Comparator compounds were then evaluated alongside ARC in the context of viability, cell cycle and apoptosis assays to establish any similarities. Following this, biological overlap was explored in detail using gene-expression analysis and kinase inhibition assays.</p> <p>Results</p> <p>Results demonstrated that sangivamycin, an extensively characterized pro-apoptotic nucleoside isolated from <it>Streptomyces</it>, had identical activity to ARC in terms of 1) cytotoxicity assays, 2) ability to induce a G₂/M block, 3) inhibitory effects on RNA/DNA/protein synthesis, 4) transcriptomic response to treatment, 5) inhibition of protein kinase C, 6) inhibition of positive transcription elongation factor b (P-TEFb), 7) inhibition of VEGF secretion, and 8) activity within hollow fiber assays. Extending ARC activity to PKC inhibition provides a molecular basis for ARC cancer selectivity and anti-angiogenic effects. Furthermore, functional overlap between ARC and sangivamycin suggests that development of ARC may benefit from a retrospective of previous sangivamycin clinical trials. However, ARC was found to be inactive in several xenograft models, likely a consequence of rapid serum clearance.</p> <p>Conclusion</p> <p>Overall, these data expand on the biological properties of ARC but suggest additional studies are required before it can be considered a clinical trials candidate.</p

Gene regulatory network subcircuit controlling a dynamic spatial pattern of signaling in the sea urchin embryo

We dissect the transcriptional regulatory relationships coordinating the dynamic expression patterns of two signaling genes, wnt8 and delta, which are central to specification of the sea urchin embryo endomesoderm. cis-Regulatory analysis shows that transcription of the gene encoding the Notch ligand Delta is activated by the widely expressed Runx transcription factor, but spatially restricted by HesC-mediated repression through a site in the delta 5′UTR. Spatial transcription of the hesC gene, however, is controlled by Blimp1 repression. Blimp1 thus represses the repressor of delta, thereby permitting its transcription. The blimp1 gene is itself linked into a feedback circuit that includes the wnt8 signaling ligand gene, and we showed earlier that this circuit generates an expanding torus of blimp1 and wnt8 expression. The finding that delta expression is also controlled at the cis-regulatory level by the blimp1-wnt8 torus-generating subcircuit now explains the progression of Notch signaling from the mesoderm to the endoderm of the developing embryo. Thus the specific cis-regulatory linkages of the gene regulatory network encode the coordinated spatial expression of Wnt and Notch signaling as they sweep outward across the vegetal plate of the embryo