Board Monitoring, Audit Committee Effectiveness and Financial Reporting Quality

This study investigates the impact of The UK Corporate Governance Code (2016) on the quality of financial reporting. A number of prior studies have examined the role of the governance mechanisms in monitoring financial reporting quality, with mixed results. This paper extends prior research by combining two streams of research on financial reporting quality, i.e., the monitoring effectiveness of board of directors and audit committees. It is hypothesised that the quality of financial reporting is significantly related to the strength of corporate governance mechanisms, including the composition of board of directors, the personal attributes of outside directors and the characteristics of audit committees. The level of earnings management as a proxy for financial reporting quality is measured by absolute discretionary accruals based on Modified Jones model (1995). By investigating FTSE 100 companies listed on the London Stock Exchange over the period 2014 to 2016, this study demonstrates that the duality of the CEO and chairman has a negative association with financial reporting quality whereas audit committee independence is positively related to financial reporting quality. These relations are statistically significant and robust to alternative specifications. Supplemental tests, by using signed discretionary accruals or change in discretionary accruals as a measure of earnings management, indicate the similar results. In addition, the supplemental tests also show that frequent board meetings have a positive impact on financial reporting quality, while the experienced outside directors have a negative impact on financial reporting quality. Additionally, results in sensitivity tests indicate that an fully independent audit committee is positively related to financial reporting quality. The results suggest that board of directors is an important factor in monitoring the quality of UK firms’ financial reporting. The results also indicate that audit committees, concerned with both income-increasing and income-decreasing earnings management, are effective in the financial reporting process by reducing the magnitude of earnings management. The results of this study provide useful guidelines to regulators, companies and academics

Improved Test-Time Adaptation for Domain Generalization

The main challenge in domain generalization (DG) is to handle the distribution shift problem that lies between the training and test data. Recent studies suggest that test-time training (TTT), which adapts the learned model with test data, might be a promising solution to the problem. Generally, a TTT strategy hinges its performance on two main factors: selecting an appropriate auxiliary TTT task for updating and identifying reliable parameters to update during the test phase. Both previous arts and our experiments indicate that TTT may not improve but be detrimental to the learned model if those two factors are not properly considered. This work addresses those two factors by proposing an Improved Test-Time Adaptation (ITTA) method. First, instead of heuristically defining an auxiliary objective, we propose a learnable consistency loss for the TTT task, which contains learnable parameters that can be adjusted toward better alignment between our TTT task and the main prediction task. Second, we introduce additional adaptive parameters for the trained model, and we suggest only updating the adaptive parameters during the test phase. Through extensive experiments, we show that the proposed two strategies are beneficial for the learned model (see Figure 1), and ITTA could achieve superior performance to the current state-of-the-art methods on several DG benchmarks. Code is available at https://github.com/liangchen527/ITTA.Comment: Accepted by CVPR 202

Membrane Interaction of Bound Ligands Contributes to the Negative Binding Cooperativity of the EGF Receptor

The epidermal growth factor receptor (EGFR) plays a key role in regulating cell proliferation, migration, and differentiation, and aberrant EGFR signaling is implicated in a variety of cancers. EGFR signaling is triggered by extracellular ligand binding, which promotes EGFR dimerization and activation. Ligand-binding measurements are consistent with a negatively cooperative model in which the ligand-binding affinity at either binding site in an EGFR dimer is weaker when the other site is occupied by a ligand. This cooperativity is widely believed to be central to the effects of ligand concentration on EGFR-mediated intracellular signaling. Although the extracellular portion of the human EGFR dimer has been resolved crystallographically, the crystal structures do not reveal the structural origin of this negative cooperativity, which has remained unclear. Here we report the results of molecular dynamics simulations suggesting that asymmetrical interactions of the two binding sites with the membrane may be responsible (perhaps along with other factors) for this negative cooperativity. In particular, in our simulations the extracellular domains of an EGFR dimer spontaneously lay down on the membrane in an orientation in which favorable membrane contacts were made with one of the bound ligands, but could not be made with the other. Similar interactions were observed when EGFR was glycosylated, as it is in vivo

Architecture and Membrane Interactions of the EGF Receptor

SummaryDimerization-driven activation of the intracellular kinase domains of the epidermal growth factor receptor (EGFR) upon extracellular ligand binding is crucial to cellular pathways regulating proliferation, migration, and differentiation. Inactive EGFR can exist as both monomers and dimers, suggesting that the mechanism regulating EGFR activity may be subtle. The membrane itself may play a role but creates substantial difficulties for structural studies. Our molecular dynamics simulations of membrane-embedded EGFR suggest that, in ligand-bound dimers, the extracellular domains assume conformations favoring dimerization of the transmembrane helices near their N termini, dimerization of the juxtamembrane segments, and formation of asymmetric (active) kinase dimers. In ligand-free dimers, by holding apart the N termini of the transmembrane helices, the extracellular domains instead favor C-terminal dimerization of the transmembrane helices, juxtamembrane segment dissociation and membrane burial, and formation of symmetric (inactive) kinase dimers. Electrostatic interactions of EGFR’s intracellular module with the membrane are critical in maintaining this coupling

Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization

Upon ligand binding, bone morphogenetic protein (BMP) receptors form active tetrameric complexes, comprised of two type I and two type II receptors, which then transmit signals to SMAD proteins. The link between receptor tetramerization and the mechanism of kinase activation, however, has not been elucidated. Here, using hydrogen deuterium exchange mass spectrometry (HDX-MS), small angle X-ray scattering (SAXS) and molecular dynamics (MD) simulations, combined with analysis of SMAD signaling, we show that the kinase domain of the type I receptor ALK2 and type II receptor BMPR2 form a heterodimeric complex via their C-terminal lobes. Formation of this dimer is essential for ligand-induced receptor signaling and is targeted by mutations in BMPR2 in patients with pulmonary arterial hypertension (PAH). We further show that the type I/type II kinase domain heterodimer serves as the scaffold for assembly of the active tetrameric receptor complexes to enable phosphorylation of the GS domain and activation of SMADs.This article is published as Agnew, C., Ayaz, P., Kashima, R. et al. Structural basis for ALK2/BMPR2 receptor complex signaling through kinase domain oligomerization. Nat Commun 12, 4950 (2021). https://doi.org/10.1038/s41467-021-25248-5. © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/

EGFR oligomerization organizes kinase-active dimers into competent signalling platforms

Epidermal growth factor receptor (EGFR) signalling is activated by ligand-induced receptor dimerization. Notably, ligand binding also induces EGFR oligomerization, but the structures and functions of the oligomers are poorly understood. Here, we use fluorophore localization imaging with photobleaching to probe the structure of EGFR oligomers. We find that at physiological epidermal growth factor (EGF) concentrations, EGFR assembles into oligomers, as indicated by pairwise distances of receptor-bound fluorophore-conjugated EGF ligands. The pairwise ligand distances correspond well with the predictions of our structural model of the oligomers constructed from molecular dynamics simulations. The model suggests that oligomerization is mediated extracellularly by unoccupied ligand-binding sites and that oligomerization organizes kinase-active dimers in ways optimal for auto-phosphorylation in trans between neighbouring dimers. We argue that ligand-induced oligomerization is essential to the regulation of EGFR signalling

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Board Monitoring, Audit Committee Effectiveness and Financial Reporting Quality

This study investigates the impact of The UK Corporate Governance Code (2016) on the quality of financial reporting. A number of prior studies have examined the role of the governance mechanisms in monitoring financial reporting quality, with mixed results. This paper extends prior research by combining two streams of research on financial reporting quality, i.e., the monitoring effectiveness of board of directors and audit committees. It is hypothesised that the quality of financial reporting is significantly related to the strength of corporate governance mechanisms, including the composition of board of directors, the personal attributes of outside directors and the characteristics of audit committees. The level of earnings management as a proxy for financial reporting quality is measured by absolute discretionary accruals based on Modified Jones model (1995). By investigating FTSE 100 companies listed on the London Stock Exchange over the period 2014 to 2016, this study demonstrates that the duality of the CEO and chairman has a negative association with financial reporting quality whereas audit committee independence is positively related to financial reporting quality. These relations are statistically significant and robust to alternative specifications. Supplemental tests, by using signed discretionary accruals or change in discretionary accruals as a measure of earnings management, indicate the similar results. In addition, the supplemental tests also show that frequent board meetings have a positive impact on financial reporting quality, while the experienced outside directors have a negative impact on financial reporting quality. Additionally, results in sensitivity tests indicate that an fully independent audit committee is positively related to financial reporting quality. The results suggest that board of directors is an important factor in monitoring the quality of UK firms’ financial reporting. The results also indicate that audit committees, concerned with both income-increasing and income-decreasing earnings management, are effective in the financial reporting process by reducing the magnitude of earnings management. The results of this study provide useful guidelines to regulators, companies and academics

Evaluation of fresh food logistics service quality using online customer reviews

Improving the quality of cold chain logistics services is a great challenge for fresh food e-commerce companies. Traditionally, the evaluation of logistics service quality has been carried out mainly through questionnaire surveys and expert groups, which are time-consuming and laborious. Unlike previous studies, in this study, we used a latent Dirichlet allocation model to explore logistics services using customer reviews on the ‘fresh food’ category of JD.com, one of China’s most popular e-commerce websites. By revising the evaluation index system for logistics service quality, we put forward an evaluation system that covers six dimensions: reliability, security, timeliness, economy, pleasantness and convenience. We then incorporated sentiment analysis technology and the TF-IDF (Term Frequency-Inverse Document Frequency) algorithm to obtain a total score for the service quality of JD’s fresh food logistics. This study provides a reference for other B2C fresh e-commerce enterprises on the implementation of logistics service quality evaluation and management

Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis.

OBJECTIVE:To evaluate the relationship between subclinical hypothyroidism (SCH) and the risk of miscarriage before 20 weeks of pregnancy. METHODS:Literature databases were searched, including the PubMed, Web of Science, Embase and Cochrane databases, from January 1, 1980, to December 31, 2015. The following search terms were used: subclinical hypothyroidism, hypothyroidism, thyroid dysfunction, thyroid hypofunction, subclinical thyroid disease, thyroid dysfunction, pregnancy loss, abortion and miscarriage. Studies comparing the prevalence of miscarriage in pregnant women with SCH with those who were euthyroid were selected. From the studies matched, the relative risk (RR) and corresponding 95% confidence interval (95% CI) were calculated to yield outcomes. All the statistical analyses were performed using Review Manager (Revman) Version 5.3 and Stata Version 12.0 software. The publication bias of the studies was assessed by forest plot and Begg's test, while the stability of the results was evaluated by sensitivity analysis. RESULTS:Nine articles satisfying the inclusion criteria were analysed. Compared to euthyroid pregnant women, patients with non-treated SCH had a higher prevalence of miscarriage (RR = 1.90, 95% CI1.59-2.27, P<0.01). Additionally, SCH patients in the international diagnostic criteria group were more likely to suffer miscarriages than those in the ATA diagnostic criteria group (χ2 = 11.493, P<0.01). Moreover, there was no difference between patients with treated SCH and euthyroid women (RR = 1.14, 95% CI0.82-1.58, P = 0.43). Compared to isolated SCH women, the miscarriage risk of SCH patients with thyroid autoimmunity (TAI) was obviously higher (RR = 2.47, 95% CI1.77-3.45, P<0.01), and isolated SCH patients also had a higher prevalence of miscarriages than euthyroid women (RR = 1.45, 95% CI1.07-1.96, P = 0.02).A heterogeneity test, forest plot and Begg's test suggested that there was no significant heterogeneity or publication bias among the included articles, while the result of sensitivity analysis showed that our study exhibited high stability. CONCLUSION:SCH is a risk factor for miscarriage in women before 20 weeks of pregnancy, and early treatments can reduce the miscarriage rate. Regardless of the diagnostic criteria used, the miscarriage rate increased as long as a pregnant woman was confirmed to have SCH. The results show that the omission diagnostic rate may increase when the ATA diagnostic criteria are used. In addition, SCH patients with TAI have a higher prevalence of miscarriage, while isolated SCH patients also have a higher miscarriage rate than euthyroid women. Thus, we recommend early treatments to avoid adverse pregnancy outcomes and complications