Murine Coronavirus Spike Glycoprotein Mediates Degree of Viral Spread, Inflammation, and Virus-Induced Immunopathology in the Central Nervous System

AbstractThe mouse hepatitis virus (MHV) spike glycoprotein is a major determinant of neurovirulence. We investigated how alterations in spike affect neurovirulence using two isogenic recombinant viruses differing exclusively in spike. S4R, containing the MHV-4 spike gene, is dramatically more neurovirulent than SA59R, containing the MHV-A59 spike gene (J. J. Phillips, M. M. Chua, E. Lavi, and S. R. Weiss, 1999, J. Virol. 73, 7752–7760). We examined the contribution of differences in cellular tropism, viral spread, and the immune response to infection to the differential neurovirulence of S4R and SA59R. MHV-4 spike-mediated neurovirulence was associated with extensive viral spread in the brain in both neurons and astrocytes. Infection of primary hippocampal neuron cultures demonstrated that S4R spread more rapidly than SA59R and suggested that spread may occur between cells in close physical contact. In addition, S4R infection induced a massive influx of lymphocytes into the brain, a higher percentage of CD8+ T cells, and a higher frequency of MHV-specific CD8+ T cells relative SA59R infection. Despite this robust and viral-specific immune response to S4R infection, infection of RAG1−/− mice suggested that immune-mediated pathology also contributes to the high neurovirulence of S4R

Corporate Governance and Earnings Management Before Share Repurchase Announcements in Singapore

Share repurchase in Singapore was legalized in 1998. It is well known that investors view share repurchase as good news. This study is based on share repurchase announcements from 2006 to 2009. The mean Cumulative Market-Adjusted Returns (CAR) for the period [0, +1] and [-1, +1] are significant at 1.25% and 1.33% respectively. In Singapore, there are positive abnormal returns following share repurchase announcements in support of the "free cash flow" hypothesis. By using the Singapore Corporate Governance Index as a proxy, the weakly governed companies exhibit the strongest, positive and significant CAR of 2.62% for the period [0, +1]. Lastly, one year prior to share repurchase announcements; companies on average manage their discretionary current accrual downwards by 1.44%. The companies with the best corporate governance manage their earnings downwards by 2.69%. In a regression, the CAR for the period [0, +1] changes by 0.1097% when the discretionary current accrual changes by 1%

Chinese big business in Indonesia. The state of capital.

Ph.DDOCTOR OF PHILOSOPH

Effects of management and media disclosures of corporate tax evasion on investor judgments

This study examines investor reactions to disclosures of corporate tax evasion by company management and the media. We were particularly interested in the issue of whether investors value corporate tax compliance from a moral perspective. We conducted an experiment in which we manipulate management disclosure strategies (no disclosure, symbolic disclosure, substantive disclosure) and the presence/absence of media disclosures in a 3 x 2 between-subjects design. Participants provided judgments of a hypothetical company’s short-term and long-term financial prospects and their willingness to maintain their investment in the company. Media disclosure of tax evasion had a significant effect on all judgments. In addition, for all judgments there was a significant interactive effect of management disclosure strategy and media disclosure. This interaction was driven by the particularly strong negative effects of media disclosure when management made no disclosure of the evasion (the “caught off guard” effect). In contrast, analysis of simple effects indicated that if management proactively discloses instances of tax evasion, subsequent disclosure by the media has no significant effect on investor judgments. We also document that, relative to a control group, management disclosure of facts regarding a tax evasion event (in the absence of media disclosure) significantly reduces investor assessments of the short-term prospects of the company and their willingness to hold the company’s stock. However, management disclosure of facts regarding tax evasion had no significant impact on investor assessments of the company’s long-term prospects. Although recent research on environmental, social and governance disclosures has documented that the specific form of management legitimation strategies (symbolic vs. substantive) has significant impacts on investor judgments, we found no evidence of such effects in our study. Supplemental analysis revealed that the perceived morality of management mediated the effects of media disclosures on investor judgments. Based on the findings we draw several conclusions. Though corporate management may be tempted to omit disclosure of tax evasion events from the financial statements, they are likely to pay a high price if the evasion is later reported by independent third parties. This appears to reflect investor reactions to management breaches of their expectations regarding moral behavior. In contrast, proactive management disclosure of the facts surrounding tax evasion events attenuates the negative effects of future media disclosures. Management disclosure of facts regarding tax evasion appears to be viewed primarily as a short-term rather than a long-term threat to a company’s prospects. Given knowledge that tax evasion has occurred, investors place little credence in management attempts to legitimize the evasion, even when such legitimation efforts describe detailed and concrete remediation strategies. Finally, investor perceptions of the morality of company management (including management commitment to ethics/integrity and corporate social responsibility) play a key role in their reactions to corporate tax evasion

Analysis of the Host Transcriptome from Demyelinating Spinal Cord of Murine Coronavirus-Infected Mice

Persistent infection of the mouse central nervous system (CNS) with mouse hepatitis virus (MHV) induces a demyelinating disease pathologically similar to multiple sclerosis and is therefore used as a model system. There is little information regarding the host factors that correlate with and contribute to MHV-induced demyelination. Here, we detail the genes and pathways associated with MHV-induced demyelinating disease in the spinal cord. High-throughput sequencing of the host transcriptome revealed that demyelination is accompanied by numerous transcriptional changes indicative of immune infiltration as well as changes in the cytokine milieu and lipid metabolism. We found evidence that a Th1-biased cytokine/chemokine response and eicosanoid-derived inflammation accompany persistent MHV infection and that antigen presentation is ongoing. Interestingly, increased expression of genes involved in lipid transport, processing, and catabolism, including some with known roles in neurodegenerative diseases, coincided with demyelination. Lastly, expression of several genes involved in osteoclast or bone-resident macrophage function, most notably TREM2 and DAP12, was upregulated in persistently infected mouse spinal cord. This study highlights the complexity of the host antiviral response, which accompany MHV-induced demyelination, and further supports previous findings that MHV-induced demyelination is immune-mediated. Interestingly, these data suggest a parallel between bone reabsorption by osteoclasts and myelin debris clearance by microglia in the bone and the CNS, respectively. To our knowledge, this is the first report of using an RNA-seq approach to study the host CNS response to persistent viral infection

Hierarchical Attention Network for Visually-aware Food Recommendation

Food recommender systems play an important role in assisting users to identify the desired food to eat. Deciding what food to eat is a complex and multi-faceted process, which is influenced by many factors such as the ingredients, appearance of the recipe, the user's personal preference on food, and various contexts like what had been eaten in the past meals. In this work, we formulate the food recommendation problem as predicting user preference on recipes based on three key factors that determine a user's choice on food, namely, 1) the user's (and other users') history; 2) the ingredients of a recipe; and 3) the descriptive image of a recipe. To address this challenging problem, we develop a dedicated neural network based solution Hierarchical Attention based Food Recommendation (HAFR) which is capable of: 1) capturing the collaborative filtering effect like what similar users tend to eat; 2) inferring a user's preference at the ingredient level; and 3) learning user preference from the recipe's visual images. To evaluate our proposed method, we construct a large-scale dataset consisting of millions of ratings from AllRecipes.com. Extensive experiments show that our method outperforms several competing recommender solutions like Factorization Machine and Visual Bayesian Personalized Ranking with an average improvement of 12%, offering promising results in predicting user preference for food. Codes and dataset will be released upon acceptance

Dual-conditioning of Sludge using Chitosan and Metal Cations

Sludge dewatering is important in sludge management and disposal. In practice, chemical conditioners are often introduced to aid sludge dewatering. This study investigated the simultaneous application of chitosan and metal cations as dual-conditioners to improve sludge dewaterability. The dewatering performance of sludge was evaluated using three common measurements, i.e. capillary suction time, specific resistance to filtration, and moisture content of the filtered sludge cake. The effectiveness of metal cations in sludge conditioning and dewatering was found, in ascending order, to be Na+ < K+ ≈ Mg2+ < Ca2+ < Al3+ < Fe3+. Dual-conditioning using chitosan and metal cations further enhanced dewaterability. Cations may have significant effects on sludge conditioning by neutralization of negative surface charges, bridging of floc components, and the salting out effect, leading to improved dewaterability when used in conjunction with chitosan