216 research outputs found

    Does Performance Breed Slack? Ownership as a Contingency to the Performance Feedback and Slack Relationship

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    Although organizational slack is a prominent construct in strategic management, it is often treated as an antecedent or enabler of other organizational outcomes, and thus our understanding of where slack comes from is underdeveloped. We draw on the behavioral theory of the firm to develop a better understanding about the antecedents of organizational slack. In so doing, we address a gap in the literature on the antecedents of slack by developing base models showing how and why performance feedback influences the three most common types of slack studied in the literature. Moreover, we contend that ownership is an important contingency that influences these relationships because different types of owners are motivated by different norms. Within a “communitarian” culture such as Japan, domestic owners generally have a multifaceted relationship with the firm and hence are motivated by norms of reciprocity and embeddedness, thereby allowing managers to adopt a stakeholder perspective. In contrast, foreign investors typically have only an arm’s-length relationship with the firm and are thus motivated by stock price, thereby putting “contractarian” pressures on managers to adopt a shareholder perspective. This domestic/foreign ownership distinction influences how resources are allocated and therefore the relationship between performance feedback and different types of slack in the firm. We further emphasize that these relationships will vary in accordance to where the slack resides: internal or external to the firm. We find general support for our hypotheses

    Polymorphisms of the Flavin containing monooxygenase 3 (FMO3) gene do not predispose to essential hypertension in Caucasians.

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    BACKGROUND: The recessive disorder trimethylaminuria is caused by defects in the FMO3 gene, and may be associated with hypertension. We investigated whether common polymorphisms of the FMO3 gene confer an increased risk for elevated blood pressure and/or essential hypertension. METHODS: FMO3 genotypes (E158K, V257M, E308G) were determined in 387 healthy subjects with ambulatory systolic and diastolic blood pressure measurements, and in a cardiovascular disease population of 1649 individuals, 691(41.9%) of whom had a history of hypertension requiring drug treatment. Haplotypes were determined and their distribution noted. RESULTS: There was no statistically significant association found between any of the 4 common haplotypes and daytime systolic blood pressure in the healthy population (p = 0.65). Neither was a statistically significant association found between the 4 common haplotypes and hypertension status among the cardiovascular disease patients (p = 0.80). CONCLUSION: These results suggest that the variants in the FMO3 gene do not predispose to essential hypertension in this population

    A prediction of cell differentiation and proliferation within a collagen-glycosaminoglycan scaffold subjected to mechanical strain and perfusive fluid flow.

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    Mesenchymal stem cell (MSC) differentiation can be influenced by biophysical stimuli imparted by the host scaffold. Yet, causal relationships linking scaffold strain magnitudes and inlet fluid velocities to specific cell responses are thus far underdeveloped. This investigation attempted to simulate cell responses in a collagen-glycosaminoglycan (CG) scaffold within a bioreactor. CG scaffold deformation was simulated using micro-computed tomography (CT) and an in-house finite element solver (FEEBE/linear). Similarly, the internal fluid velocities were simulated using the afore-mentioned microCT dataset with a computational fluid dynamics solver (ANSYS/CFX). From the ensuing cell-level mechanics, albeit octahedral shear strain or fluid velocity, the proliferation and differentiation of the representative cells were predicted from deterministic functions. Cell proliferation patterns concurred with previous experiments. MSC differentiation was dependent on the level of CG scaffold strain and the inlet fluid velocity. Furthermore, MSC differentiation patterns indicated that specific combinations of scaffold strains and inlet fluid flows cause phenotype assemblies dominated by single cell types. Further to typical laboratory procedures, this predictive methodology demonstrated loading-specific differentiation lineages and proliferation patterns. It is hoped these results will enhance in-vitro tissue engineering procedures by providing a platform from which the scaffold loading applications can be tailored to suit the desired tissue

    Genetic Introgression and the Survival of Florida Panther Kittens

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    Estimates of survival for the young of a species are critical for population models. These models can often be improved by determining the effects of management actions and population abundance on this demographic parameter. We used multiple sources of data collected during 1982–2008 and a live-recapture dead-recovery modeling framework to estimate and model survival of Florida panther (Puma concolor coryi) kittens (age 0–1 year). Overall, annual survival of Florida panther kittens was 0.323 ± 0.071 (SE), which was lower than estimates used in previous population models. In 1995, female pumas from Texas (P. c. stanleyana) were released into occupied panther range as part of an intentional introgression program to restore genetic variability. We found that kitten survival generally increased with degree of admixture: F1 admixed and backcrossed to Texas kittens survived better than canonical Florida panther and backcrossed to canonical kittens. Average heterozygosity positively influenced kitten and older panther survival, whereas index of panther abundance negatively influenced kitten survival. Our results provide strong evidence for the positive population-level impact of genetic introgression on Florida panthers. Our approach to integrate data from multiple sources was effective at improving robustness as well as precision of estimates of Florida panther kitten survival, and can be useful in estimating vital rates for other elusive species with sparse data

    Sudden onset headache in a post-partum young female

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     We present the case of a 33 year old female presenting with acute neurological signs including right sided neglect and confusion four days postpartum. The original non-contrast CT brain demonstrated an acute left temporal intraparenchymal hemorrhage. A cerebral catheter angiogram was performed and demonstrated the typical appearances of RCVS (Reversible cerebral vasoconstriction syndrome)

    Monitoring Fast Superconducting Qubit Dynamics Using A Neural Network

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    Weak measurements of a superconducting qubit produce noisy voltage signals that are weakly correlated with the qubit state. To recover individual quantum trajectories from these noisy signals, traditional methods require slow qubit dynamics and substantial prior information in the form of calibration experiments. Monitoring rapid qubit dynamics, e.g., during quantum gates, requires more complicated methods with increased demand for prior information. Here, we experimentally demonstrate an alternative method for accurately tracking rapidly driven superconducting qubit trajectories that uses a long short-term memory (LSTM) artificial neural network with minimal prior information. Despite few training assumptions, the LSTM produces trajectories that include qubit-readout resonator correlations due to a finite detection bandwidth. In addition to revealing rotated measurement eigenstates and a reduced measurement rate in agreement with theory for a fixed drive, the trained LSTM also correctly reconstructs evolution for an unknown drive with rapid modulation. Our work enables new applications of weak measurements with faster or initially unknown qubit dynamics, such as the diagnosis of coherent errors in quantum gates

    Exploiting pre-rRNA processing in Diamond Blackfan anemia gene discovery and diagnosis

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    Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single-copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS. We report here a novel deletion in a child that presented such a diagnostic challenge and prompted development of a novel functional assay that can assist in the diagnosis of a significant fraction of patients with DBA. The ribosomal proteins affected in DBA are required for pre-rRNA processing, a process which can be interrogated to monitor steps in the maturation of 40S and 60S ribosomal subunits. In contrast to prior methods used to assess pre-rRNA processing, the assay reported here, based on capillary electrophoresis measurement of the maturation of rRNA in pre-60S ribosomal subunits, would be readily amenable to use in diagnostic laboratories. In addition to utility as a diagnostic tool, we applied this technique to gene discovery in DBA, resulting in the identification of RPL31 as a novel DBA gene. Am. J. Hematol. 89:985-991, 2014. (c) 2014 Wiley Periodicals, Inc

    Uropathogenic Escherichia coli infection-induced epithelial trained immunity impacts urinary tract disease outcome

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    Previous urinary tract infections (UTIs) can predispose one to future infections; however, the underlying mechanisms affecting recurrence are poorly understood. We previously found that UTIs in mice cause differential bladder epithelial (urothelial) remodelling, depending on disease outcome, that impacts susceptibility to recurrent UTI. Here we compared urothelial stem cell (USC) lines isolated from mice with a history of either resolved or chronic uropathogenic Escherichia coli (UPEC) infection, elucidating evidence of molecular imprinting that involved epigenetic changes, including differences in chromatin accessibility, DNA methylation and histone modification. Epigenetic marks in USCs from chronically infected mice enhanced caspase-1-mediated cell death upon UPEC infection, promoting bacterial clearance. Increased Ptgs2os2 expression also occurred, potentially contributing to sustained cyclooxygenase-2 expression, bladder inflammation and mucosal wounding-responses associated with severe recurrent cystitis. Thus, UPEC infection acts as an epi-mutagen reprogramming the urothelial epigenome, leading to urothelial-intrinsic remodelling and training of the innate response to subsequent infection

    New hints towards a precision medicine strategy for IDH wild-type glioblastoma.

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    Glioblastoma represents the most common primary malignancy of the central nervous system in adults and remains a largely incurable disease. The elucidation of disease subtypes based on mutational profiling, gene expression and DNA methylation has so far failed to translate into improved clinical outcomes. However, new knowledge emerging from the subtyping effort in the IDH-wild-type setting may provide directions for future precision therapies. Here, we review recent learnings in the field, and further consider how tumour microenvironment differences across subtypes may reveal novel contexts of vulnerability. We discuss recent treatment approaches and ongoing trials in the IDH-wild-type glioblastoma setting, and propose an integrated discovery stratagem incorporating multi-omics, single-cell technologies and computational approaches

    Ibrutinib restores immune cell numbers and function in first-line and relapsed/refractory chronic lymphocytic leukemia

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    © 2020 The Authors Ibrutinib positively modulates many T-cell subsets in chronic lymphocytic leukemia (CLL). To understand ibrutinib\u27s effects on the broader landscape of immune cell populations, we comprehensively characterized changes in circulating counts of 21 immune blood cell subsets throughout the first year of treatment in patients with relapsed/refractory (R/R) CLL (n = 55, RESONATE) and previously untreated CLL (n = 50, RESONATE-2) compared with untreated age-matched healthy donors (n = 20). Ibrutinib normalized abnormal immune cell counts to levels similar to those of age-matched healthy donors. Ibrutinib significantly decreased pathologically high circulating B cells, regulatory T cells, effector/memory CD4+ and CD8+ T cells (including exhausted and chronically activated T cells), natural killer (NK) T cells, and myeloid-derived suppressor cells; preserved naive T cells and NK cells; and increased circulating classical monocytes. T-cell function was assessed in response to T-cell receptor stimulation in patients with R/R CLL (n = 21) compared with age-matched healthy donors (n = 18). Ibrutinib significantly restored T-cell proliferative ability, degranulation, and cytokine secretion. Over the same period, ofatumumab or chlorambucil did not confer the same spectrum of normalization as ibrutinib in multiple immune subsets. These results establish that ibrutinib has a significant and likely positive impact on circulating malignant and nonmalignant immune cells and restores healthy T-cell function
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