Restoring Trust in Corporate Directors: The Disney Standard and the ‘New’ Good Faith

The purpose of this Article is to explore the parameters and potential impact of the good faith standard articulated in Disney V and clarified in Stone. Part I begins with a brief review of the historical impact of the tension between entrepreneurial freedom and managerial accountability, and Part II explains why the Disney standard differs significantly from the traditional understanding of good faith as the absence of subjective bad faith. Part III points out that the court\u27s use of the language of bad faith to articulate the new good faith may undercut the effectiveness of the standard. It urges further clarification of the difference between the absence of good faith and the presence of bad faith to ensure that the Disney standard will not be reduced to a mere semantic variation on the traditional duty of loyalty applicable only in the presence of improper-i.e., subjectively bad -motivation. Finally, Part IV examines the Disney standard\u27s potential to serve as a vehicle for restoring trust in corporate directors and argues that the new good faith has the capacity to serve this important function, but only if the courts utilize the doctrine to require corporate directors to engage actively in oversight of the business and affairs of the entities entrusted to them

Positive regulation of meiotic DNA double-strand break formation by activation of the DNA damage checkpoint kinase Mec1(ATR)

During meiosis, formation and repair of programmed DNA double-strand breaks (DSBs) create genetic exchange between homologous chromosomes-a process that is critical for reductional meiotic chromosome segregation and the production of genetically diverse sexually reproducing populations. Meiotic DSB formation is a complex process, requiring numerous proteins, of which Spo11 is the evolutionarily conserved catalytic subunit. Precisely how Spo11 and its accessory proteins function or are regulated is unclear. Here, we use Saccharomyces cerevisiae to reveal that meiotic DSB formation is modulated by the Mec1(ATR) branch of the DNA damage signalling cascade, promoting DSB formation when Spo11-mediated catalysis is compromised. Activation of the positive feedback pathway correlates with the formation of single-stranded DNA (ssDNA) recombination intermediates and activation of the downstream kinase, Mek1. We show that the requirement for checkpoint activation can be rescued by prolonging meiotic prophase by deleting the NDT80 transcription factor, and that even transient prophase arrest caused by Ndt80 depletion is sufficient to restore meiotic spore viability in checkpoint mutants. Our observations are unexpected given recent reports that the complementary kinase pathway Tel1(ATM) acts to inhibit DSB formation. We propose that such antagonistic regulation of DSB formation by Mec1 and Tel1 creates a regulatory mechanism, where the absolute frequency of DSBs is maintained at a level optimal for genetic exchange and efficient chromosome segregation

Staphylococcus aureus virulence factors identified by using a high-throughput Caenorhabditis elegans-killing model

Staphylococcus aureus is an important human pathogen that is also able to kill the model nematode Caenorhabditis elegans. We constructed a 2,950-member Tn917 transposon insertion library in S. aureus strain NCTC 8325. Twenty-one of these insertions exhibited attenuated C. elegans killing, and of these, 12 contained insertions in different genes or chromosomal locations. Ten of these 12 insertions showed attenuated killing phenotypes when transduced into two different S. aureus strains, and 5 of the 10 mutants correspond to genes that have not been previously identified in signature-tagged mutagenesis studies. These latter five mutants were tested in a murine renal abscess model, and one mutant harboring an insertion in nagD exhibited attenuated virulence. Interestingly, Tn917 was shown to have a very strong bias for insertions near the terminus of DNA replication

Spatial Engineering of Osteochondral Tissue Constructs Through Microfluidically Directed Differentiation of Mesenchymal Stem Cells

The development of tissue engineered osteochondral units has been slowed by a number of technical hurdles associated with recapitulating their heterogeneous nature ex vivo. Subsequently, numerous approaches with respect to cell sourcing, scaffolding composition, and culture media formulation have been pursued, which have led to high variability in outcomes and ultimately the lack of a consensus bioprocessing strategy. As such, the objective of this study was to standardize the design process by focusing on differentially supporting formation of cartilaginous and bony matrix by a single cell source in a spatially controlled manner within a single material system. A cell-polymer solution of bovine mesenchymal stem cells and agarose was cast against micromolds of a serpentine network and stacked to produce tissue constructs containing two independent microfluidic networks. Constructs were fluidically connected to two controlled flow loops and supplied with independently tuned differentiation parameters for chondrogenic and osteogenic induction, respectively. Constructs receiving inductive media showed differential gene expression of both chondrogenic and osteogenic markers in opposite directions along the thickness of the construct that was recapitulated at the protein level with respect to collagens I, II, and X. A control group receiving noninductive media showed homogeneous expression of these biomarkers measured in lower concentrations at both the mRNA and protein level. This work represents an important step in the rational design of engineered osteochondral units through establishment of an enabling technology for further optimization of scaffolding formulations and bioprocessing conditions toward the production of commercially viable osteochondral tissue products

The Global Stratotype Section and Point (GSSP) for the base of the Katian Stage of the Upper Ordovician Series at Black Knob Ridge, Southeastern Oklahoma, USA

The International Subcomission on Ordovician Stratigraphy (ISOS) of the International Commission on Stratigraphy (ICS) recently defined the base of the global Upper Ordovician Series to be at the first appearance datum (FAD) of the graptolite species Nemagraptus gracilis in the Fågelsång GSSP in southern Sweden. This designation recognized the tremendous utility for global correlation of the first appearance of a cosmopolitan taxon that occurs within a consistent succession of other first appearance datums (e.g., Finney and Bergström, 1986; Bergström et al., 2000). Current efforts by the ISOS have focused on subdividing the Upper Ordovician into three stages and choosing appropriate levels and stratotypes for the bases of the middle and upper of these stages. The purpose of the present report is to describe the GSSP of the middle stage, for which the name Katian Stage was approved by the ISOS and ratified by the ICS in 2006 (Bergström et al., 2006). For a recent review of the long process of developing the new subdivisions of the Ordovician, see Finney (2005)

An Ordovician Global Reference Section Recently Selected in Oklahoma

Ordovician fossil faunas are characterized by a marked biogeographic differentiation that results in a minimal similarity between most North American faunas and those of major Ordovician areas elsewhere in the world. This provincial distribution of most fossils has led to establishment of different schemes of fossil-based regional stages in, for instance, North America, Baltoscandia, China, and the British Isles. Because these chrono-stratigraphic units have been largely based on shelly fossils with distributions restricted to a particular region, it has been impossible in most cases to establish a precise international correlation of these regional stages. Furthermore, some general terms, such as the Middle Ordovician;\u27 have a vastly different stratigraphic scope in different parts of the world causing confusion among stratigraphers and non-stratigraphers alike. Indeed, in view of the fact that many of today\u27s geology studies are of more than regional nature, there has been an urgent need for an international chronostratigraphic classification

Cervical dystonia incidence and diagnostic delay in a multiethnic population.

BackgroundCurrent cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized.ObjectivesTo determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization.MethodsWe identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration.ResultsCD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68).ConclusionsCD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society

Impairment of early fracture healing by skeletal muscle trauma is restored by FK506

BACKGROUND: Heightened local inflammation due to muscle trauma or disease is associated with impaired bone regeneration. METHODS: We hypothesized that FK506, an FDA approved immunomodulatory compound with neurotrophic and osteogenic effects, will rescue the early phase of fracture healing which is impaired by concomitant muscle trauma in male (~4 months old) Lewis rats. FK506 (1 mg/kg; i.p.) or saline was administered systemically for 14 days after an endogenously healing tibia osteotomy was created and fixed with an intermedullary pin, and the overlying tibialis anterior (TA) muscle was either left uninjured or incurred volumetric muscle loss injury (6 mm full thickness biopsy from middle third of the muscle). RESULTS: The salient observations of this study were that 1) concomitant TA muscle trauma impaired recovery of tibia mechanical properties 28 days post-injury, 2) FK506 administration rescued the recovery of tibia mechanical properties in the presence of concomitant TA muscle trauma but did not augment mechanical recovery of an isolated osteotomy (no muscle trauma), 3) T lymphocytes and macrophage presence within the traumatized musculature were heightened by trauma and attenuated by FK506 3 days post-injury, and 4) T lymphocyte but not macrophage presence within the fracture callus were attenuated by FK506 at 14 days post-injury. FK506 did not improve TA muscle isometric torque production CONCLUSION: Collectively, these findings support the administration of FK506 to ameliorate healing of fractures with severe muscle trauma comorbidity. The results suggest one potential mechanism of action is a reduction in local T lymphocytes within the injured musculoskeletal tissue, though other mechanisms to include direct osteogenic effects of FK506 require further investigation