CEO’s Inside Debt and Dynamics of Capital Structure

Debt-type compensation (inside debt) exacerbates the divergence in risk preferences between the chief executive officer (CEO) and shareholders and, in turn, affects capital structure decisions. An excessively risk-averse CEO tends to use less debt than the shareholders desire, reduce debtquickly when the firm is overlevered, but is reluctant to increase debt when the firm is underlevered. We find that higher CEO’s inside debt ratio (i.e., inside debt as a percentage of total incentive compensation) is associated with lower firm leverage and faster (slower) leverage adjustments toward the shareholders’ desired level for overlevered (underlevered) firms. The CEO’s inside debt ratio most conducive to capital structure rebalancing is around 10% of the firm’s market debt ratio

Papillary Thyroid Carcinoma Variants are Characterized by Co-dysregulation of Immune and Cancer Associated Genes.

Papillary thyroid carcinoma (PTC) variants exhibit different prognosis, but critical characteristics of PTC variants that contribute to differences in pathogenesis are not well-known. This study aims to characterize dysregulated immune-associated and cancer-associated genes in three PTC subtypes to explore how the interplay between cancer and immune processes causes differential prognosis. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to identify dysregulated genes in each variant. The dysregulation profiles of the subtypes were compared using functional pathways clustering and correlations to relevant clinical variables, genomic alterations, and microRNA regulation. We discovered that the dysregulation profiles of classical PTC (CPTC) and the tall cell variant (TCPTC) are similar and are distinct from that of the follicular variant (FVPTC). However, unique cancer or immune-associated genes are associated with clinical variables for each subtype. Cancer-related genes MUC1, FN1, and S100-family members were the most clinically relevant in CPTC, while APLN and IL16, both immune-related, were clinically relevant in FVPTC. RAET-family members, also immune-related, were clinically relevant in TCPTC. Collectively, our data suggest that dysregulation of both cancer and immune associated genes defines the gene expression landscapes of PTC variants, but different cancer or immune related genes may drive the phenotype of each variant

High-speed propulsion of flexible nanowire motors: Theory and experiments

Micro/nano-scale propulsion has attracted considerable recent attention due to its promise for biomedical applications such as targeted drug delivery. In this paper, we report on a new experimental design and theoretical modelling of high-speed fuel-free magnetically-driven propellers which exploit the flexibility of nanowires for propulsion. These readily prepared nanomotors display both high dimensional propulsion velocities (up to ≈ 21 μm s−1) and dimensionless speeds (in body lengths per revolution) when compared with natural microorganisms and other artificial propellers. Their propulsion characteristics are studied theoretically using an elastohydrodynamic model which takes into account the elasticity of the nanowire and its hydrodynamic interaction with the fluid medium. The critical role of flexibility in this mode of propulsion is illustrated by simple physical arguments, and is quantitatively investigated with the help of an asymptotic analysis for small-amplitude swimming. The theoretical predictions are then compared with experimental measurements and we obtain good agreement. Finally, we demonstrate the operation of these nanomotors in a real biological environment (human serum), emphasizing the robustness of their propulsion performance and their promise for biomedical applications

Proximal Causal Inference without Uniqueness Assumptions

We consider identification and inference about a counterfactual outcome mean when there is unmeasured confounding using tools from proximal causal inference (Miao et al. [2018], Tchetgen Tchetgen et al. [2020]). Proximal causal inference requires existence of solutions to at least one of two integral equations. We motivate the existence of solutions to the integral equations from proximal causal inference by demonstrating that, assuming the existence of a solution to one of the integral equations, $\sqrt{n}$-estimability of a linear functional (such as its mean) of that solution requires the existence of a solution to the other integral equation. Solutions to the integral equations may not be unique, which complicates estimation and inference. We construct a consistent estimator for the solution set for one of the integral equations and then adapt the theory of extremum estimators to find from the estimated set a consistent estimator for a uniquely defined solution. A debiased estimator for the counterfactual mean is shown to be root-$n$ consistent, regular, and asymptotically semiparametrically locally efficient under additional regularity conditions.Comment: Added journal reference and supplemen

Genetic Screens in Human Cells Using the CRISPR-Cas9 System

The bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–Cas9 system for genome editing has greatly expanded the toolbox for mammalian genetics, enabling the rapid generation of isogenic cell lines and mice with modified alleles. Here, we describe a pooled, loss-of-function genetic screening approach suitable for both positive and negative selection that uses a genome-scale lentiviral single-guide RNA (sgRNA) library. sgRNA expression cassettes were stably integrated into the genome, which enabled a complex mutant pool to be tracked by massively parallel sequencing. We used a library containing 73,000 sgRNAs to generate knockout collections and performed screens in two human cell lines. A screen for resistance to the nucleotide analog 6-thioguanine identified all expected members of the DNA mismatch repair pathway, whereas another for the DNA topoisomerase II (TOP2A) poison etoposide identified TOP2A, as expected, and also cyclin-dependent kinase 6, CDK6. A negative selection screen for essential genes identified numerous gene sets corresponding to fundamental processes. Last, we show that sgRNA efficiency is associated with specific sequence motifs, enabling the prediction of more effective sgRNAs. Collectively, these results establish Cas9/sgRNA screens as a powerful tool for systematic genetic analysis in mammalian cells.National Institutes of Health (U.S.) (CA103866)National Human Genome Research Institute (U.S.) (2U54HG003067-10)National Science Foundation (U.S.

Functional interplay between NTP leaving group and base pair recognition during RNA polymerase II nucleotide incorporation revealed by methylene substitution.

RNA polymerase II (pol II) utilizes a complex interaction network to select and incorporate correct nucleoside triphosphate (NTP) substrates with high efficiency and fidelity. Our previous 'synthetic nucleic acid substitution' strategy has been successfully applied in dissecting the function of nucleic acid moieties in pol II transcription. However, how the triphosphate moiety of substrate influences the rate of P-O bond cleavage and formation during nucleotide incorporation is still unclear. Here, by employing β,γ-bridging atom-'substituted' NTPs, we elucidate how the methylene substitution in the pyrophosphate leaving group affects cognate and non-cognate nucleotide incorporation. Intriguingly, the effect of the β,γ-methylene substitution on the non-cognate UTP/dT scaffold (∼3-fold decrease in kpol) is significantly different from that of the cognate ATP/dT scaffold (∼130-fold decrease in kpol). Removal of the wobble hydrogen bonds in U:dT recovers a strong response to methylene substitution of UTP. Our kinetic and modeling studies are consistent with a unique altered transition state for bond formation and cleavage for UTP/dT incorporation compared with ATP/dT incorporation. Collectively, our data reveals the functional interplay between NTP triphosphate moiety and base pair hydrogen bonding recognition during nucleotide incorporation

RN-Net: Reservoir Nodes-Enabled Neuromorphic Vision Sensing Network

Event-based cameras are inspired by the sparse and asynchronous spike representation of the biological visual system. However, processing the event data requires either using expensive feature descriptors to transform spikes into frames, or using spiking neural networks that are expensive to train. In this work, we propose a neural network architecture, Reservoir Nodes-enabled neuromorphic vision sensing Network (RN-Net), based on simple convolution layers integrated with dynamic temporal encoding reservoirs for local and global spatiotemporal feature detection with low hardware and training costs. The RN-Net allows efficient processing of asynchronous temporal features, and achieves the highest accuracy of 99.2% for DVS128 Gesture reported to date, and one of the highest accuracy of 67.5% for DVS Lip dataset at a much smaller network size. By leveraging the internal device and circuit dynamics, asynchronous temporal feature encoding can be implemented at very low hardware cost without preprocessing and dedicated memory and arithmetic units. The use of simple DNN blocks and standard backpropagation-based training rules further reduces implementation costs.Comment: 12 pages, 5 figures, 4 table

Unravelling immunoglobulin G Fc N-glycosylation: A dynamic marker potentiating predictive, preventive and personalised medicine

Multiple factors influence immunoglobulin G glycosylation, which in turn affect the glycoproteins’ function on eliciting an anti-inflammatory or pro-inflammatory response. It is prudent to underscore these processes when considering the use of immunoglobulin G N-glycan moieties as an indication of disease presence, progress, or response to therapeutics. It has been demonstrated that the altered expression of genes that encode enzymes involved in the biosynthesis of immunoglobulin G N-glycans, receptors, or complement factors may significantly modify immunoglobulin G effector response, which is important for regulating the immune system. The immunoglobulin G N-glycome is highly heterogenous; however, it is considered an interphenotype of disease (a link between genetic predisposition and environmental exposure) and so has the potential to be used as a dynamic biomarker from the perspective of predictive, preventive, and personalised medicine. Undoubtedly, a deeper understanding of how the multiple factors interact with each other to alter immunoglobulin G glycosylation is crucial. Herein we review the current literature on immunoglobulin G glycoprotein structure, immunoglobulin G Fc glycosylation, associated receptors, and complement factors, the downstream effector functions, and the factors associated with the heterogeneity of immunoglobulin G glycosylation