Highly active cationic cobalt(II) hydroformylation catalysts

© 2020 American Association for the Advancement of Science. All rights reserved. The cobalt complexes HCo(CO)4 and HCo(CO)3(PR3) were the original industrial catalysts used for the hydroformylation of alkenes through reaction with hydrogen and carbon monoxide to produce aldehydes. More recent and expensive rhodium-phosphine catalysts are hundreds of times more active and operate under considerably lower pressures. Cationic cobalt(II) bisphosphine hydrido-carbonyl catalysts that are far more active than traditional neutral cobalt(I) catalysts and approach rhodium catalysts in activity are reported here. These catalysts have low linear-to-branched (L:B) regioselectivity for simple linear alkenes. However, owing to their high alkene isomerization activity and increased steric effects due to the bisphosphine ligand, they have high L:B selectivities for internal alkenes with alkyl branches. These catalysts exhibit long lifetimes and substantial resistance to degradation reactions

Association of autistic traits with depression from childhood to age 18 years

Importance Population-based studies following trajectories of depression in autism spectrum disorders (ASD) from childhood into early adulthood are rare. The role of genetic confounding and of potential environmental intermediaries, such as bullying, in any associations is unclear. Objectives To compare trajectories of depressive symptoms from ages 10 to 18 years for children with or without ASD and autistic traits, to assess associations between ASD and autistic traits and an International Statistical Classification of Diseases, 10th Revision (ICD-10) depression diagnosis at age 18 years, and to explore the importance of genetic confounding and bullying. Design, Setting, and Participants Longitudinal study of participants in the Avon Longitudinal Study of Parents and Children birth cohort in Bristol, United Kingdom, followed up through age 18 years. Data analysis was conducted from January to November 2017. Main Outcomes and Measures Depressive symptoms were assessed using the Short Mood and Feelings Questionnaire (SMFQ) at 6 time points between ages 10 and 18 years. An ICD-10 depression diagnosis at 18 years was established using the Clinical Interview Schedule–Revised. Exposures were ASD diagnosis and 4 dichotomized autistic traits (social communication, coherence, repetitive behavior, and sociability). An autism polygenic risk score was derived using the Psychiatric Genomics Consortium autism discovery genome-wide association study summary data. Bullying was assessed at ages 8, 10, and 13 years. Results The maximum sample with complete data was 6091 for the trajectory analysis (48.8% male) and 3168 for analysis of depression diagnosis at age 18 years (44.4% male). Children with ASD and autistic traits had higher average SMFQ depressive symptom scores than the general population at age 10 years (eg, for social communication 5.55 [95% CI, 5.16-5.95] vs 3.73 [95% CI, 3.61-3.85], for ASD 7.31 [95% CI, 6.22-8.40] vs 3.94 [95% CI, 3.83-4.05], remaining elevated in an upward trajectory until age 18 years (eg, for social communication 7.65 [95% CI, 6.92-8.37] vs 6.50 [95% CI, 6.29-6.71], for ASD 7.66 [95% CI, 5.96-9.35] vs 6.62 [95% CI, 6.43-6.81]). Social communication impairments were associated with depression at age 18 years (adjusted relative risk, 1.68; 95% CI, 1.05-2.70), and bullying explained a substantial proportion of this risk. There was no evidence of confounding by the autism polygenic risk score. Analysis in larger samples using multiple imputation led to similar but more precise results. Conclusions and Relevance Children with ASD and ASD traits have higher depressive symptom scores than the general population by age 10 years, which persist to age 18 years, particularly in the context of bullying. Social communication impairments are an important autistic trait in relation to depression. Bullying, as an environmental intermediary, could be a target for interventions

Reactivation of a developmentally silenced embryonic globin gene

The α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, the most common single gene disorders. Here, we address mechanisms regulating the embryonically expressed α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, the ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) of open, acetylated chromatin and interacts with the α-globin super-enhancer. By contrast, in adult erythroid cells, the ζ-gene is packaged within a small (~10 kb) sub-domain of hypoacetylated, facultative heterochromatin within the acetylated sub-TAD and that it no longer interacts with its enhancers. The ζ-gene can be partially re-activated by acetylation and inhibition of histone de-acetylases. In addition to suggesting therapies for severe α-thalassemia, these findings illustrate the general principles by which reactivation of developmental genes may rescue abnormalities arising from mutations in their adult paralogues

On the Bounds of Function Approximations

Within machine learning, the subfield of Neural Architecture Search (NAS) has recently garnered research attention due to its ability to improve upon human-designed models. However, the computational requirements for finding an exact solution to this problem are often intractable, and the design of the search space still requires manual intervention. In this paper we attempt to establish a formalized framework from which we can better understand the computational bounds of NAS in relation to its search space. For this, we first reformulate the function approximation problem in terms of sequences of functions, and we call it the Function Approximation (FA) problem; then we show that it is computationally infeasible to devise a procedure that solves FA for all functions to zero error, regardless of the search space. We show also that such error will be minimal if a specific class of functions is present in the search space. Subsequently, we show that machine learning as a mathematical problem is a solution strategy for FA, albeit not an effective one, and further describe a stronger version of this approach: the Approximate Architectural Search Problem (a-ASP), which is the mathematical equivalent of NAS. We leverage the framework from this paper and results from the literature to describe the conditions under which a-ASP can potentially solve FA as well as an exhaustive search, but in polynomial time.Comment: Accepted as a full paper at ICANN 2019. The final, authenticated publication will be available at https://doi.org/10.1007/978-3-030-30487-4_3

Ginseng and Ganoderma lucidum Use after Breast Cancer Diagnosis and Quality of Life: A Report from the Shanghai Breast Cancer Survival Study

Objective: To evaluate associations between quality of life (QOL) and use of ginseng and Ganoderma lucidum (G. lucidum) among breast cancer survivors. Methods: Included in this study were 4,149 women with breast cancer who participated in the Shanghai Breast Cancer Survival Study. Ginseng use was assessed at 6-, 18-, and 36-month post-diagnosis surveys; G. lucidum use was assessed at the 6- and 36-month surveys. QOL was evaluated at the 6- and 36-month surveys. Multiple linear regression models were used to examine associations between ginseng and G.lucidum use and QOL assessed at the 36-month survey, with adjustment for potential confounders and baseline QOL. Results: At 6 months post-diagnosis, 14.2 % of participants reported regular use of ginseng and 58.8 % reported use of G. lucidum. We found no significant associations between ginseng use at 6, 18, and 36 months post-diagnosis and participants’ total QOL score or individual scores for psychological, physical, or social well-being. Post-diagnosis G. lucidum use was positively associated with social well-being (adjusted mean difference: 1.26; 95 % CI: 0.66, 1.86), but was inversely associated with physical well-being (adjusted mean difference: 21.16; 95 % CI: 21.86, 20.47) with a dose-response pattern observed for cumulative number of times of use (P for trend,0.001 for both). Conclusion: We found no evidence that post-diagnosis ginseng use improved the QOL of breast cancer survivors. Post

Assessing managerial power theory: A meta-analytic approach to understanding the determinants of CEO compensation

Although studies about the determinants of CEO compensation are ubiquitous, the balance of evidence for one of the more controversial theoretical approaches, managerial power theory, remains inconclusive. The authors provide a meta-analysis of 219 U.S.-based studies, focusing on the relationships between indicators of managerial power and levels of CEO compensation and CEO pay-performance sensitivities. The results indicate that managerial power theory is well equipped for predicting core compensation variables such as total cash and total compensation but less so for predicting the sensitivity of pay to performance. In most situations where CEOs are expected to have power over the pay setting process, they receive significantly higher levels of total cash and total compensation. In contrast, where boards are expected to have more power, CEOs receive lower total cash and total compensation. In addition, powerful directors also appear to be able to establish tighter links between CEO compensation and firm performance and can accomplish this even in the face of powerful CEOs. The authors discuss the implications for theory and research regarding the determinants of executive compensation

Quantitative High-Throughput Screening Identifies 8-Hydroxyquinolines as Cell-Active Histone Demethylase Inhibitors

Small molecule modulators of epigenetic processes are currently sought as basic probes for biochemical mechanisms, and as starting points for development of therapeutic agents. N(epsilon)-Methylation of lysine residues on histone tails is one of a number of post-translational modifications that together enable transcriptional regulation. Histone lysine demethylases antagonize the action of histone methyltransferases in a site- and methylation state-specific manner. N(epsilon)-Methyllysine demethylases that use 2-oxoglutarate as co-factor are associated with diverse human diseases, including cancer, inflammation and X-linked mental retardation; they are proposed as targets for the therapeutic modulation of transcription. There are few reports on the identification of templates that are amenable to development as potent inhibitors in vivo and large diverse collections have yet to be exploited for the discovery of demethylase inhibitors

Uptake of alkaline earth metals in Alcyonarian spicules (Octocorallia)

Alcyonarian corals (Octocorallia) living in shallow tropical seas produce spicules of high-Mg calcite with ∼13 mol% MgCO3. We cultured the tropical alcyonarian coral Rhythisma fulvum in experiments varying temperature (19–32 °C) and pH (8.15–8.44). Alkalinity depletion caused by spicule formation systematically varied in the temperature experiments increasing from 19 to 29 °C. Spicules were investigated for their elemental ratios (Mg/Ca, Sr/Ca) using ICP-OES, δ44/40Ca using TIMS, as well as δ18O and δ13C by IRMS. Mg/Ca increased with temperature from 146 to 164 mmol/mol, in good agreement with the range observed for marine inorganic calcite. Mg/Ca increased by 1.0 ± 0.4 mmol/mol/°C, similar to the sensitivity of Miliolid foraminifera. The pH experiments revealed a linear relationship between Mg/Ca and carbonate ion concentration of +0.03 ± 0.02 mmol/mol/μMol. Sr/Ca ranges from 2.5 to 2.9 mmol/mol being in good agreement with other high-Mg calcites. Temperature and pH experiments showed linear dependencies of Sr/Ca matching inorganic calcite trends and pointing to a decoupling of crystal precipitation rate and calcification rate. Ca isotopes range between 0.7‰ and 0.9‰ in good agreement with aragonitic scleractinian corals and calcitic coccoliths. Presumably Ca isotopes are fractionated by a biological mechanism that may be independent of the skeletal mineralogy. We observe no temperature trend, but a significant decrease of δ44/40Ca with increasing pH. This inverse correlation may characterise biologically controlled intracellular calcification. Oxygen isotope ratios are higher than expected for isotopic equilibrium with a temperature sensitivity of −0.15 ± 0.03‰/°C. Carbon isotope ratios are significantly lower than expected for equilibrium and positively correlated with temperature with a slope of 0.20 ± 0.04‰/°C. Many of our observations on trace element incorporation in R. fulvum may be explained by inorganic processes during crystal formation, which do not comply with the intracellular mode of calcification in Alcyonarian corals. The observed elemental and isotopic compositions, however, could be explained if the partitioning caused by biological mechanisms mimics the effects of inorganic processes