Market Conditions and Fund Flows: Evidence from Hedge Funds

This paper investigates whether market conditions affect fund investor behaviour in the hedge fund industry, especially the volatility in the up and down markets. Using a sample of 5,254 individual hedge funds from January 1994 to December 2009, we find that hedge fund investors tend to invest less during up and down-volatile markets.They also adopt different investment strategies in these two market conditions. When market is calm and relatively predictable, there is almost no difference in their behaviors between up and down markets. We also find that smart money effect exists over both 3- and 12-month periods under all market conditions except volatile markets. A further investigation suggests that the observed smart money effect is largely driven by hedge fund performance persistence, which is present and significant is quiet markets only. The findings are relevant to portfolio theories concerning investor recognition of upside and downside volatilities

Scalable production of iPSC-derived human neurons to identify tau-lowering compounds by high-content screening

Lowering total tau levels is an attractive therapeutic strategy for Alzheimer's disease and other tauopathies. High-throughput screening in neurons derived from human induced pluripotent stem cells (iPSCs) is a powerful tool to identify tau-targeted therapeutics. However, such screens have been hampered by heterogeneous neuronal production, high cost and low yield, and multi-step differentiation procedures. We engineered an isogenic iPSC line that harbors an inducible neurogenin 2 transgene, a transcription factor that rapidly converts iPSCs to neurons, integrated at the AAVS1 locus. Using a simplified two-step protocol, we differentiated these iPSCs into cortical glutamatergic neurons with minimal well-to-well variability. We developed a robust high-content screening assay to identify tau-lowering compounds in LOPAC and identified adrenergic receptors agonists as a class of compounds that reduce endogenous human tau. These techniques enable the use of human neurons for high-throughput screening of drugs to treat neurodegenerative disease

Phytonutrient genistein is a survival factor for pancreatic β-cells via GPR30-mediated mechanism

We previously discovered that phytonutrient genistein rapidly activates cAMP signaling in β-cells and improves islet mass in diabetic mice. However, the mechanism underlying these actions of genistein is still unclear. Here, we show that pharmacological or molecular inhibition of Gαs blocked genistein-stimulated adenylate cyclase activity in plasma membrane and intracellular cAMP production in INS1 cells and islets. Further, genistein stimulation of cAMP generation was abolished in islets exposed to a specific GPR30 inhibitor G15 or islets from GPR30 deficient (GPR30−/−) mice. In vivo, dietary provision of genistein (0.5 g/kg diet) significantly mitigated streptozotocin-induced hyperglycemia in male WT mice, which was associated with improved blood insulin levels and pancreatic islet mass and survival, whereas these effects were absent in Gpr30−/− mice. Genistein treatment promoted survival of INS1 cells and human islets chronically exposed to palmitate and high glucose. At molecular level, genistein activated CREB phosphorylation and subsequently induced Bcl-2 expression, and knockdown of CREB diminished the protective effect of genistein on β-cells induced by lipoglucotoxicity. Finally, deletion of GPR30 in β-cells or islets ablated genistein-induced CREB phosphorylation and its cytoprotective effect. These findings demonstrate that genistein is a survival factor for β-cells via GPR30-initiated, Gαs-mediated activation of CREB

Enantiodivergent Formation of C−P Bonds: Synthesis of P‑Chiral Phosphines and Methylphosphonate Oligonucleotides

Phosphorus Incorporation (PI, abbreviated Π) reagents for the modular, scalable, and stereospecific synthesis of chiral phosphines and methylphosphonate nucleotides are reported. Synthesized from translimonene oxide, this reagent class displays an unexpected reactivity profile and enables access to chemical space distinct from that of the Phosphorus−Sulfur Incorporation reagents previously disclosed. Here, the adaptable phosphorus(V) scaffold enables sequential addition of carbon nucleophiles to produce a variety of enantiopure C−P building blocks. Addition of three carbon nucleophiles to Π, followed by stereospecific reduction, affords useful P-chiral phosphines; introduction instead of a single methyl group reveals the first stereospecific synthesis of methylphosphonate oligonucleotide precursors. While both Π enantiomers are available, only one isomer is requiredthe order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design

Greenhouse gas emissions from U.S. crude oil pipeline accidents:1968 to 2020

Abstract Crude oil pipelines are considered as the lifelines of energy industry. However, accidents of the pipelines can lead to severe public health and environmental concerns, in which greenhouse gas (GHG) emissions, primarily methane, are frequently overlooked. While previous studies examined fugitive emissions in normal operation of crude oil pipelines, emissions resulting from accidents were typically managed separately and were therefore not included in the emission account of oil systems. To bridge this knowledge gap, we employed a bottom-up approach to conducted the first-ever inventory of GHG emissions resulting from crude oil pipeline accidents in the United States at the state level from 1968 to 2020, and leveraged Monte Carlo simulation to estimate the associated uncertainties. Our results reveal that GHG emissions from accidents in gathering pipelines (~720,000 tCO2e) exceed those from transmission pipelines (~290,000 tCO2e), although significantly more accidents have occurred in transmission pipelines (6883 cases) than gathering pipelines (773 cases). Texas accounted for over 40% of total accident-related GHG emissions nationwide. Our study contributes to enhanced accuracy of the GHG account associated with crude oil transport and implementing the data-driven climate mitigation strategies

Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury

Peripheral nerve injury induces substantial molecular changes in the somatosensory system that leads to maladaptive plasticity and cause neuropathic pain. Understanding the molecular pathways responsible for the development of neuropathic pain is essential to the development of novel rationally designed therapeutics. Although lipids make up to half of the dry weight of the spinal cord, their relation with the development of neuropathic pain is poorly understood. We aimed to elucidate the regulation of spinal lipids in response to neuropathic peripheral nerve injury in mice by utilizing matrix-assisted laser desorption/ionization imaging mass spectrometry, which allows visualization of lipid distribution within the cord. We found that arachidonic acid (AA) containing [PC(diacyl-16:0/20:4)+K]+ was increased temporarily at superficial ipsilateral dorsal horn seven days after spared nerve injury (SNI). The spatiotemporal changes in lipid concentration resembled microglia activation as defined by ionized calcium binding adaptor molecule 1 (Iba1) immunohistochemistry. Suppression of microglial function through minocycline administration resulted in attenuation of hypersensitivity and reduces [PC(diacyl-16:0/20:4)+K]+ elevation in the spinal dorsal horn. These data suggested that AA containing [PC(diacyl-16:0/20:4)+K]+ is related to hypersensitivity evoked by SNI and implicate microglial cell activation in this lipid production

Risk assessment of heavy metals in soils contaminated by smelting waste for the perspective of chemical fraction and spatial distribution

The heavy metals contamination in soil has attracted increasing attention. In this study, the main objective was to determine three heavy metals (Cd, Pb, and Cr) of soils contaminated by smelting waste, and to evaluate pollution risk. The Pb (15.48 mg/kg) and Cd (311.39 mg/kg) mean concentrations exceeded the national standard, while Cr (48.60 mg/kg) concentration did not exceed. The Heavy metal fractions analysis showed that three heavy metals were dominated by FeMn oxides fraction (Fe-Mn). The correlation and cluster analysis indicated that there was significant correlation between Cd and Pb (0.55< r < 0.96), while Cr was not correlation to Cd and Pb. The environmental pollution of heavy metals was assessed by the ratio of secondary phase and primary phase (RSP). The result showed that RSP values of Cd, Pb, and Cr range from 13.05–54.28, 16.11–4.97 and 1.61–52.33, which indicated soil was serious contaminated by them. These results showed that smelting waste discharge led to this smelter soil being seriously contaminated by multiple heavy metals which have a tendency to transport and accumulate into deep soil due to their high fractional transformation

Numerical modelling of FRP-reinforced masonry walls under in-plane seismic loading

This paper describes the development of Finite Element (FE) models for the study of the behaviour of unreinforced and Basalt Fibre Reinforced Polymer (BFRP) externally reinforced masonry walls under the action of in-plane seismic loading. Validated against experimental tests, the FE models were used to accurately predict the shear strength and reflect damage progression in multi-leaf masonry walls under in-plane cyclic loading, including the propagation of cracks beneath the BFRP reinforcement. The models have the potential to be used in practice to predict the behaviour and shear capacity of unreinforced and FRP-reinforced masonry walls

Discrete element simulation of particle motion in ball mills based on similarity

Discrete element (DE) simulation of a ball mill with a large number of particles is challenging when each particle is considered. Similarity principle could be adopted to reduce the number of particles in a simulation whilst still maintaining the accurate flow behaviour of particles. This paper presents a scaling relationship between particle gravitational acceleration, mill diameter and mill rotational speed. A series of scaled simulations of particle motion with different mill diameters are carried out. Consistent motion of a single particle and multiple particles in ball mills with different diameters and rotational speeds verifies the proposed relationship, which could be an effective approach to reduce the size of simulations for ball mills