Boards strategizing in liminal spaces: Process and practice, formal and informal.

Boards operate notionally in a liminal, nonhierarchical space, neither inside the company nor outside, creating ambiguity between service and control functions and fostering tolerance of it. With repeated corporate governance crises, however, new prescriptions institutionalized in law, regulation, and codes of conduct have added significance to the control side, marked by monitoring and compliance tasks. Taking a cue from the strategy process and strategy-as-practice literatures, this study revisits the work of directors on the service side: their engagement in strategizing. Formalization of board processes has led to greater structure and reduced the liminality of the board. Using interviews with 20 directors from a range of organization types, this study finds that directors experiment respond to increased institutionalization of board practice by seeking out new liminal spaces and informal practices, with implications for theory of boards, board activities, and public policy

Spatiotemporally Complete Condensation in a Non-Poissonian Exclusion Process

We investigate a non-Poissonian version of the asymmetric simple exclusion process, motivated by the observation that coarse-graining the interactions between particles in complex systems generically leads to a stochastic process with a non-Markovian (history-dependent) character. We characterize a large family of one-dimensional hopping processes using a waiting-time distribution for individual particle hops. We find that when its variance is infinite, a real-space condensate forms that is complete in space (involves all particles) and time (exists at almost any given instant) in the thermodynamic limit. The mechanism for the onset and stability of the condensate are both rather subtle, and depends on the microscopic dynamics subsequent to a failed particle hop attempts.Comment: 5 pages, 5 figures. Version 2 to appear in PR

Bid participates in genotoxic drug-induced apoptosis of HeLa cells and is essential for death receptor ligands' apoptotic and synergistic effects

Background: The BH3-only protein Bid is an important component of death receptor-mediated caspase activation. Bid is cleaved by caspase-8 or -10 into t-Bid, which translocates to mitochondria and triggers the release of caspase-activating factors. Bid has also been reported to be cleaved by other proteases. Methodology/Principal Findings: To test the hypothesis that Bid is a central mediator of stress-induced apoptosis, we investigated the effects of a small molecule Bid inhibitor on stress-induced apoptosis, and generated HeLa cells deficient for Bid. Stable knockdown of bid lead to a pronounced resistance to Fas/CD95- and TRAIL-induced caspase activation and apoptosis, and significantly increased clonogenic survival. While Bid-deficient cells were equally sensitive to ER stress-induced apoptosis, they showed moderate, but significantly reduced levels of apoptosis, as well as increased clonogenic survival in response to the genotoxic drugs Etoposide, Oxaliplatin, and Doxorubicin. Similar effects were observed using the Bid inhibitor BI6C9. Interestingly, Bid-deficient cells were dramatically protected from apoptosis when subtoxic concentrations of ER stressors, Etoposide or Oxaliplatin were combined with subtoxic TRAIL concentrations. Conclusions/Significance: Our data demonstrate that Bid is central for death receptor-induced cell death and participates in anti-cancer drug-induced apoptosis in human cervical cancer HeLa cells. They also show that the synergistic effects of TRAIL in combination with either ER stressors or genotoxic anti-cancer drugs are nearly exclusively mediated via an increased activation of Bid-induced apoptosis signalling

Cost effectiveness of school-located influenza vaccination programs for elementary and secondary school children.

BackgroundStudies have noted variations in the cost-effectiveness of school-located influenza vaccination (SLIV), but little is known about how SLIV's cost-effectiveness may vary by targeted age group (e.g., elementary or secondary school students), or vaccine consent process (paper-based or web-based). Further, SLIV's cost-effectiveness may be impacted by its spillover effect on practice-based vaccination; prior studies have not addressed this issue.MethodsWe performed a cost-effectiveness analysis on two SLIV programs in upstate New York in 2015-2016: (a) elementary school SLIV using a stepped wedge design with schools as clusters (24 suburban and 18 urban schools) and (b) secondary school SLIV using a cluster randomized trial (16 suburban and 4 urban schools). The cost-per-additionally-vaccinated child (i.e., incremental cost-effectiveness ratio (ICER)) was estimated by dividing the incremental SLIV intervention cost by the incremental effectiveness (i.e., the additional number of vaccinated students in intervention schools compared to control schools). We performed deterministic analyses, one-way sensitivity analyses, and probabilistic analyses.ResultsThe overall effectiveness measure (proportion of children vaccinated) was 5.7 and 5.5 percentage points higher, respectively, in intervention elementary (52.8%) and secondary schools (48.2%) than grade-matched control schools. SLIV programs vaccinated a small proportion of children in intervention elementary (5.2%) and secondary schools (2.5%). In elementary and secondary schools, the ICER excluding vaccine purchase was $85.71 and$86.51 per-additionally-vaccinated-child, respectively. When additionally accounting for observed spillover impact on practice-based vaccination, the ICER decreased to $80.53 in elementary schools -- decreasing substantially in secondary schools. (to$53.40). These estimates were higher than the published practice-based vaccination cost (median = $25.50, mean =$45.48). Also, these estimates were higher than our 2009-2011 urban SLIV program mean costs ($65) due to additional costs for use of a new web-based consent system ($12.97 per-additionally-vaccinated-child) and higher project coordination costs in 2015-2016. One-way sensitivity analyses showed that ICER estimates were most sensitive to the SLIV effectiveness.ConclusionsSLIV raises vaccination rates and may increase practice-based vaccination in primary care practices. While these SLIV programs are effective, to be as cost-effective as practice-based vaccination our SLIV programs would need to vaccinate more students and/or lower the costs for consent systems and project coordination.Trial registrationClinicalTrials.gov NCT02227186 (August 25, 2014), updated NCT03137667 (May 2, 2017)

MicroRNA-224 is Readily Detectable in Urine of Individuals with Diabetes Mellitus and is a Potential Indicator of Beta-Cell Demise.

MicroRNA (miRNA) are a class of non-coding, 19-25 nucleotide RNA critical for network-level regulation of gene expression. miRNA serve as paracrine signaling molecules. Using an unbiased array approach, we previously identified elevated levels of miR-224 and miR-103 to be associated with a monogenic form of diabetes; HNF1A-MODY. miR-224 is a novel miRNA in the field of diabetes. We sought to explore the role of miR-224 as a potential biomarker in diabetes, and whether such diabetes-associated-miRNA can also be detected in the urine of patients. Absolute levels of miR-224 and miR-103 were determined in the urine of n = 144 individuals including carriers of a HNF1A mutation, participants with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and normal controls. Expression levels were correlated with clinical and biochemical parameters. miR-224 was significantly elevated in the urine of carriers of a HNF1A mutation and participants with T1DM. miR-103 was highly expressed in urine across all diabetes cohorts when compared to controls. For both miR-224 and-103, we found a significant correlation between serum and urine levels (p \u3c 0.01). We demonstrate that miRNA can be readily detected in the urine independent of clinical indices of renal dysfunction. We surmise that the differential expression levels of miR-224 in both HNF1A-MODY mutation carriers and T1DM may be an attempt to compensate for beta-cell demise

Motoneurons secrete angiogenin to induce RNA cleavage in astroglia.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder affecting motoneurons. Mutations in angiogenin, encoding a member of the pancreatic RNase A superfamily, segregate with ALS. We previously demonstrated that angiogenin administration shows promise as a neuroprotective therapeutic in studies using transgenic ALS mice and primary motoneuron cultures. Its mechanism of action and target cells in the spinal cord, however, are largely unknown. Using mixed motoneuron cultures, motoneuron-like NSC34 cells, and primary astroglia cultures as model systems, we here demonstrate that angiogenin is a neuronally secreted factor that is endocytosed by astroglia and mediates neuroprotection in paracrine. We show that wild-type angiogenin acts unidirectionally to induce RNA cleavage in astroglia, while the ALS-associated K40I mutant is also secreted and endocytosed, but fails to induce RNA cleavage. Angiogenin uptake into astroglia requires heparan sulfate proteoglycans, and engages clathrin-mediated endocytosis. We show that this uptake mechanism exists for mouse and human angiogenin, and delivers a functional RNase output. Moreover, we identify syndecan 4 as the angiogenin receptor mediating the selective uptake of angiogenin into astroglia. Our data provide new insights into the paracrine activities of angiogenin in the nervous system, and further highlight the critical role of non-neuronal cells in the pathogenesis of ALS

Polarization instabilities in a two-photon laser

We describe the operating characteristics of a new type of quantum oscillator that is based on a two-photon stimulated emission process. This two-photon laser consists of spin-polarized and laser-driven $^{39}$K atoms placed in a high-finesse transverse-mode-degenerate optical resonator, and produces a beam with a power of $\sim$0.2 $\mu$W at a wavelength of 770 nm. We observe complex dynamical instabilities of the state of polarization of the two-photon laser, which are made possible by the atomic Zeeman degeneracy. We conjecture that the laser could emit polarization-entangled twin beams if this degeneracy is lifted.Comment: Accepted by Physical Review Letters. REVTeX 4 pages, 4 EPS figure

Facilitating the analysis of a UK national blood service supply chain using distributed simulation

In an attempt to investigate blood unit ordering policies, researchers have created a discrete-event model of the UK National Blood Service (NBS) supply chain in the Southampton area of the UK. The model has been created using Simul8, a commercial-off-the-shelf discrete-event simulation package (CSP). However, as more hospitals were added to the model, it was discovered that the length of time needed to perform a single simulation severely increased. It has been claimed that distributed simulation, a technique that uses the resources of many computers to execute a simulation model, can reduce simulation runtime. Further, an emerging standardized approach exists that supports distributed simulation with CSPs. These CSP Interoperability (CSPI) standards are compatible with the IEEE 1516 standard The High Level Architecture, the defacto interoperability standard for distributed simulation. To investigate if distributed simulation can reduce the execution time of NBS supply chain simulation, this paper presents experiences of creating a distributed version of the CSP Simul8 according to the CSPI/HLA standards. It shows that the distributed version of the simulation does indeed run faster when the model reaches a certain size. Further, we argue that understanding the relationship of model features is key to performance. This is illustrated by experimentation with two different protocols implementations (using Time Advance Request (TAR) and Next Event Request (NER)). Our contribution is therefore the demonstration that distributed simulation is a useful technique in the timely execution of supply chains of this type and that careful analysis of model features can further increase performance

A method for gene-based pathway analysis using genomewide association study summary statistics reveals nine new type 1 diabetes associations.

Pathway analysis can complement point-wise single nucleotide polymorphism (SNP) analysis in exploring genomewide association study (GWAS) data to identify specific disease-associated genes that can be candidate causal genes. We propose a straightforward methodology that can be used for conducting a gene-based pathway analysis using summary GWAS statistics in combination with widely available reference genotype data. We used this method to perform a gene-based pathway analysis of a type 1 diabetes (T1D) meta-analysis GWAS (of 7,514 cases and 9,045 controls). An important feature of the conducted analysis is the removal of the major histocompatibility complex gene region, the major genetic risk factor for T1D. Thirty-one of the 1,583 (2%) tested pathways were identified to be enriched for association with T1D at a 5% false discovery rate. We analyzed these 31 pathways and their genes to identify SNPs in or near these pathway genes that showed potentially novel association with T1D and attempted to replicate the association of 22 SNPs in additional samples. Replication P-values were skewed (P=9.85×10-11) with 12 of the 22 SNPs showing P<0.05. Support, including replication evidence, was obtained for nine T1D associated variants in genes ITGB7 (rs11170466, P=7.86×10-9), NRP1 (rs722988, 4.88×10-8), BAD (rs694739, 2.37×10-7), CTSB (rs1296023, 2.79×10-7), FYN (rs11964650, P=5.60×10-7), UBE2G1 (rs9906760, 5.08×10-7), MAP3K14 (rs17759555, 9.67×10-7), ITGB1 (rs1557150, 1.93×10-6), and IL7R (rs1445898, 2.76×10-6). The proposed methodology can be applied to other GWAS datasets for which only summary level data are available.This is the final version. It was first published by Wiley at http://onlinelibrary.wiley.com/doi/10.1002/gepi.21853/abstract

Optical Spectroscopy of Type Ia Supernovae

We present 432 low-dispersion optical spectra of 32 Type Ia supernovae (SNe Ia) that also have well-calibrated light curves. The coverage ranges from 6 epochs to 36 epochs of spectroscopy. Most of the data were obtained with the 1.5m Tillinghast telescope at the F. L. Whipple Observatory with typical wavelength coverage of 3700-7400A and a resolution of ~7A. The earliest spectra are thirteen days before B-band maximum; two-thirds of the SNe were observed before maximum brightness. Coverage for some SNe continues almost to the nebular phase. The consistency of the method of observation and the technique of reduction makes this an ideal data set for studying the spectroscopic diversity of SNe Ia.Comment: Accepted for publication in the Astronomical Journal, 109 pages (including data table), 44 figures, full resolution figures at http://www.noao.edu/noao/staff/matheson/Iaspec.ps.g