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Violations of no-arbitrage conditions measure the shadow cost of intermediary constraints. Intermediary asset pricing and intertemporal hedging together imply that the risk of these constraints tightening is priced. We describe a “forward CIP trading strategy” that bets on CIP violations shrinking and show that its returns help identify the price of this risk. This strategy yields the highest returns for currency pairs associated with the carry trade. The strategy’s risk substantially contributes to the volatility of the stochastic discount factor, is correlated with both other near-arbitrages and intermediary wealth measures, and appears to be consistently priced across various asset classes. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.

As a key means to elevate low-carbon energy transformation in China, multi-energy microgrid accelerates the construction of new power systems. In order to scientifically evaluate the benefits of multi-energy microgrids, we proposed a benefit evaluation index system from the dimensions of economy, reliability, low carbonization, and intelligence. Considering the relationship between the evaluation indicators, this paper innovatively proposed a multi-energy microgrid benefit evaluation model based on AHP-VWT-MEEM. In addition, this paper selected different multi-energy microgrid demonstration projects in the China Southern Power Grid Company Limited’s region for example analysis. In the example analysis, through the comparison of the comprehensive benefits of the three projects, the comprehensive benefit of the project 3 is the best. On this basis, from the specific configuration plan of Project 3, it can be concluded that the configuration of larger capacity thermal storage can realize the "thermal decoupling" of cogeneration, thereby improving the flexible adjustment capability of the demonstration area, promoting the consumption of renewable energy, and obtaining more considerable comprehensive benefits. At the same time, it is pointed out that the comprehensive benefit evaluation result can be improved by appropriately reducing the investment cost of project 3.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of patients who receive the most intensive treatment inevitably suffer disease relapse, likely resulting from the persistence of drug‑resistant leukemia stem cells (LSCs). AML cells especially LSCs are highly dependent on mitochondrial oxidative phosphorylation (OXPHOS) for survival, but the mechanism involved in OXPHOS hyperactivity is unclear and a noncytotoxic strategy to inhibit OXPHOS is lacking. Here, we demonstrate for the first time that ZDHHC21 palmitoyltransferase serves as a key regulator of OXPHOS hyperactivity in AML cells. The depletion/inhibition of ZDHHC21 effectively induced myeloid differentiation and weakened stemness potential by inhibiting OXPHOS in AML cells. Interestingly, FLT3-ITD mutated AML cells expressed significantly higher levels of ZDHHC21 and exhibited better sensitivity to ZDHHC21 inhibition. Mechanistically, ZDHHC21 specifically catalyzed the palmitoylation of mitochondrial kinase AK2 and further activated OXPHOS in leukemic blasts. Inhibition of ZDHHC21 arrested the in vivo growth of AML cells and extended the survival of mice inoculated with AML cell lines and PDX-AML blasts. Moreover, targeting ZDHHC21 to suppress OXPHOS markedly eradicated AML blasts and enhanced chemotherapy efficacy in relapsed/refractory leukemia. Together, these findings not only uncover a new biological function of palmitoyltransferase ZDHHC21 in regulating AML oxidative phosphorylation, but also indicate that ZDHHC21 inhibition is a promising therapeutic regimen for patients with AML, especially relapsed/refractory leukemia.

In most acute promyelocytic leukemia (APL) cells, promyelocytic leukemia (PML) fuses to retinoic acid receptor α (RARα) due to chromosomal translocation, thus generating PML/RARα oncoprotein, which is a relatively stable oncoprotein for degradation in APL. Elucidating the mechanism regulating the stability of PML/RARα may help to degrade PML/RARα and eradicate APL cells. Here, we describe a deubiquitinase (DUB)-involved regulatory mechanism for the maintenance of PML/RARα stability and develop a novel pharmacological approach to degrading PML/RARα by inhibiting DUB. We utilized a DUB siRNA library to identify the ovarian tumor protease (OTU) family member deubiquitinase YOD1 as a critical DUB of PML/RARα. Suppression of YOD1 promoted the degradation of PML/RARα, thus inhibiting APL cells and prolonging the survival time of APL cell-bearing mice. Subsequent phenotypic screening of small molecules allowed us to identify ubiquitin isopeptidase inhibitor I (G5) as the first YOD1 pharmacological inhibitor. As expected, G5 notably degraded PML/RARα protein and eradicated APL, particularly drug-resistant APL cells. Importantly, G5 also showed a strong killing effect on primary patient-derived APL blasts. Overall, our study not only reveals the DUB-involved regulatory mechanism on PML/RARα stability and validates YOD1 as a potential therapeutic target for APL, but also identifies G5 as a YOD1 inhibitor and a promising candidate for APL, particularly drug-resistant APL treatment.

Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML/RARα, which destroys the architecture of PML nuclear bodies (NBs). PML NBs are critical to tumor suppression, and their disruption mediated by PML/RARα accelerates APL pathogenesis. However, the mechanisms of PML NB disruption remain elusive. Here, we reveal that the failure of NB assembly in APL results from neddylation-induced aberrant phase separation of PML/RARα. Mechanistically, PML/RARα is neddylated in the RARα moiety, and this neddylation enhances its DNA-binding ability and further impedes the phase separation of the PML moiety, consequently disrupting PML NB construction. Accordingly, deneddylation of PML/RARα restores its phase separation process to reconstruct functional NBs and activates RARα signaling, thereby suppressing PML/RARα-driven leukemogenesis. Pharmacological inhibition of neddylation by MLN4924 eradicates APL cells both in vitro and in vivo. Our work elucidates the neddylation-destroyed phase separation mechanism for PML/RARα-driven NB disruption and highlights targeting neddylation for APL eradication.

Checkpoint kinase 1 (CHK1) plays an important role in the DNA damage response pathway, being a potential anti-cancer drug target. In this study, we used a strategy for trifluoromethyl substitution to obtain orally bioavailable CHK1 inhibitors to overcome the limitations of lead compound 1, which can only be administered intravenously. After detailed investigation, we identified compound 6c as an oral CHK1 inhibitor, which demonstrated a considerably higher plasma exposure in mice. Compound 6c also showed good kinase selectivity. Moreover, it exhibited a significant antiproliferative effect in MV-4-11 cells singly and a synergistic effect in combination with gemcitabine in HT-29, A549, and RPMI-8226 cells. Additionally, compound 6c could inhibit tumor growth in the MV-4-11 xenograft mouse model. The combination of 6c and gemcitabine exhibited synergistic effect in the HT-29 xenograft mouse model. Thus, compound 6c was found to be a selective and oral potential anticancer CHK1 inhibitor.

Inspired by natural wood, novel Ce0·7Zr0·3O2 catalyst with hierarchical porous structure, W–CeZr, was fabricated using wood template method by utilizing catheter pores and pits in poplar. W–CeZr catalyst was then used for selective catalytic reduction of NO with NH3 for the first time. Compared with conventional Ce0·7Zr0·3O2 catalyst (C–CeZr), W–CeZr catalyst mimicked biological microstructure of wood and exhibited much greater low-temperature activity than C–CeZr, i.e., NO conversion for W–CeZr was 100% in the range of 250–350 °C, while that for C–CeZr was only 58.1% at 250 °C. Based on a series of characterization techniques, this effect can be attributed to an increase in surface area (m2·g−1), enrichment of Ce3+, and enrichment of surface-active oxygen species by 133.7%, 60%, and 59.5% compared to C–CeZr, respectively. In situ diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy results show that more activated reactants were present on the surface of W–CeZr because of its stronger surface acidity, as well as redox and oxygen storage abilities.

We show that the role of unsecured, short-term wholesale funding for global banks has changed significantly in the post-financial-crisis regulatory environment. Global banks mainly use such funding to finance liquid, near risk-free arbitrage positions—in particular, the interest on excess reserves arbitrage and the covered interest rate parity arbitrage. In this environment, we examine the response of global banks to a large negative wholesale funding shock as a result of the U.S. money market mutual fund reform implemented in 2016. In contrast to past episodes of wholesale funding dry-ups, we find that the primary response of global banks to the reform was a cutback in arbitrage positions that relied on unsecured funding, rather than a reduction in loan provision.

The discovery of effective therapeutic treatments for cancer via cell differentiation instead of antiproliferation remains a great challenge. Cyclin-dependent kinase 2 (CDK2) inactivation, which overcomes the differentiation arrest of acute myeloid leukemia (AML) cells, may be a promising method for AML treatment. However, there is no available selective CDK2 inhibitor. More importantly, the inhibition of only the enzymatic function of CDK2 would be insufficient to promote notable AML differentiation. To further validate the role and druggability of CDK2 involved in AML differentiation, a suitable chemical tool is needed. Therefore, we developed first-in-class CDK2-targeted proteolysis-targeting chimeras (PROTACs), which promoted rapid and potent CDK2 degradation in different cell lines without comparable degradation of other targets, and induced remarkable differentiation of AML cell lines and primary patient cells. These data clearly demonstrated the practicality and importance of PROTACs as alternative tools for verifying CDK2 protein functions.

To serve as an electron transport layer (ETL) or a buffer layer for the third-generation solar cells, a compact and uniform gallium nitride (GaN) thin layer with suitable energy level is needed. Meanwhile, it is also meaningful to explore its low-temperature deposition especially on transparent electrodes. In this work, GaN thin films have been deposited on fluorine-doped tin oxide (FTO) glass substrate for the first time by plasma-enhanced atomic layer deposition (PEALD) technology. 280–300 °C is identified as the optimized deposition temperature for forming a compact and uniform n-type GaN layer on FTO substrate. The 50–200 PEALD cycles of GaN layers show an amorphous structure, and their bandgap values ranging from 3.95 eV to 3.58 eV have been displayed. Interestingly, as the GaN thickness increases, Fermi level moves upward obviously along with a reduction of conduction band minimum (CBM) value as well as an increase of valence band maximum (VBM) value. The thickness-dependent band structure is preliminarily explained as the relaxation of compressive stress and increased carrier concentration for a thicker GaN layer. The above situation enables us to regulate the energy level of GaN layer via thickness control, and thus accelerates its future application in new generation solar cells.

In this paper, we present a refined convergence analysis for a simple yet powerful method for computing a symmetric low-rank orthogonal approximation of a symmetric tensor proposed in the literature. The significance is that the assumption guaranteeing the global convergence is vastly relaxed to only on an input parameter of this algorithm.

In most acute promyelocytic leukemia (APL) cells, promyelocytic leukemia (PML) fuses to retinoic acid receptor

We document a triangular relationship in that a stronger dollar goes hand in hand with larger deviations from covered interest parity (CIP) and contractions of cross-border bank lending in dollars. We argue that underpinning the triangle is the role of the dollar as a key barometer of risk-taking capacity in global capital markets. (JEL F23, F31, G15, G21)

In this study, a luminescent material of wood-based carbon quantum dots (CQDs)/Ce0.7Zr0.3O2 with a regular, uniform shape, and a high color purity was synthesized by a facile method. CexZr1−xO2 solid-solution oxides (x = 0.7) were prepared by a hydrothermal method, and CQDs were adsorbed on the as-obtained Ce0.7Zr0.3O2 nanoparticles. The crystal structure was identified by powder X-ray diffraction and Rietveld refinement. In addition, the effect of adsorbed CQDs on the luminescence properties of Ce0.7Zr0.3O2 was systematically investigated by Raman spectroscopy, elemental analysis, electron spin resonance spectroscopy, and photoluminescence spectroscopy, as well as decay curve and quantum yield (QY) measurements. Herein, a promising strategy of surface engineering, that is, reduction of the surface defect concentration in Ce0.7Zr0.3O2 by the adsorption of CQDs to decrease the nonradiative transition processes at defect sites was described. As expected, the adsorption of CQDs decreased the Ce–O bond length and the surface defect concentration of Ce0.7Zr0.3O2, thereby effectively decreasing the nonradiative transition processes and suppressing fluorescence quenching. Hence, CQDs/Ce0.7Zr0.3O2 with a perfect cubic structure exhibits a performance improvement in terms of the luminescence and QY value. Furthermore, a light-emitting diode device was fabricated using as-synthesized CQDs/Ce0.7Zr0.3O2, emitting apparent yellow light with a high color purity (93.3%), with International Commission on Illumination coordinates of (0.5239, 0.4531), and a low correlated color temperature (2271 K) under a driven current of 60 mA, suggesting that CQDs/Ce0.7Zr0.3O2 exhibits potential for practical applications.

The covered interest rate parity (CIP) condition is a fundamental arbitrage relationship in international finance. In this chapter, we review its breakdown during the Global Financial Crisis and its continued failure in the subsequent decade. We review how to measure CIP deviations, discuss the drivers of CIP deviations, and the implications of CIP deviations for global financial markets.

We provide a comprehensive account of the evolution of the currency composition of sovereign and corporate external borrowing by emerging markets from 2003 to 2017. We show that a higher reliance on foreign currency debt by the corporate sector is associated with higher sovereign default risk. We introduce local currency sovereign debt and private sector currency mismatch into a standard sovereign debt model to examine how the currency composition of corporate borrowing affects the sovereign’s incentive to inflate or default. A calibration of the model generates the empirical patterns of sovereign credit risk.

Environment-friendly medium-density fiberboards (MDFs) prepared using sodium lignosulfonate/chitosan adhesives (L/C) show potential in environment-friendly wood-based panel application. However, the synthesis mechanism of this adhesive and the relationships between synthesis mechanism and bonding performance were not discussed in depth. Herein, the synthesis mechanism of L/C was explored in detail based on characterizations of L/C with different mass ratios of sodium lignosulfonate to chitosan by Fourier-transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction. For L/C with different mass ratios of sodium lignosulfonate to chitosan, the corresponding bonding performance was also determined based on characterizations of mechanical and dimensional performance of MDFs. Results showed a 3D network structure of L/C formed through the hydrogen linkages among hydroxyl groups in sodium lignosulfonate and hydroxyl and amino groups in chitosan, amide linkages resulted from reaction between carbonyl groups in sodium lignosulfonate and amino groups in chitosan, and sulfonamide linkages originated from reaction between sulfonic groups in sodium lignosulfonate and amino groups in chitosan. The mechanical performance of MDF was closely related to the 3D network and amino groups of L/C, while the dimensional performance of MDF was negatively affected by sodium lignosulfonate. The MDFs with 1:3 and 1:2 mass ratios of sodium lignosulfonate to chitosan showed superior mechanical properties and comparable dimensional performance with a commercial panel.

Although molecular targeted therapies have recently displayed therapeutic effects in acute myeloid leukemia (AML), limited response and acquired resistance remain common problems. Numerous studies have associated autophagy, an essential degradation process involved in the cellular response to stress, with the development and therapeutic response of cancers including AML. Thus, we review studies on the role of autophagy in AML development and summarize the linkage between autophagy and several recurrent genetic abnormalities in AML, highlighting the potential of capitalizing on autophagy modulation in targeted therapy for AML. Abbreviations: AML: acute myeloid leukemia; AMPK: AMP-activated protein kinase; APL: acute promyelocytic leukemia; ATG: autophagy related; ATM: ATM serine/threonine kinase; ATO: arsenic trioxide; ATRA: all trans retinoic acid; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; BET proteins, bromodomain and extra-terminal domain family; CMA: chaperone-mediated autophagy; CQ: chloroquine; DNMT, DNA methyltransferase; DOT1L: DOT1 like histone lysine methyltransferase; FLT3: fms related receptor tyrosine kinase 3; FIS1: fission, mitochondrial 1; HCQ: hydroxychloroquine; HSC: hematopoietic stem cell; IDH: isocitrate dehydrogenase; ITD: internal tandem duplication; KMT2A/MLL: lysine methyltransferase 2A; LSC: leukemia stem cell; MDS: myelodysplastic syndromes; MTORC1: mechanistic target of rapamycin kinase complex 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NPM1: nucleophosmin 1; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PML: PML nuclear body scaffold; ROS: reactive oxygen species; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SAHA: vorinostat; SQSTM1: sequestosome 1; TET2: tet methylcytosine dioxygenase 2; TKD: tyrosine kinase domain; TKI: tyrosine kinase inhibitor; TP53/p53: tumor protein p53; ULK1: unc-51 like autophagy activating kinase 1; VPA: valproic acid; WDFY3/ALFY: WD repeat and FYVE domain containing 3.

The discovery of effective therapeutic treatments for cancer via cell differentiation instead of antiproliferation remains a great challenge. Cyclin-dependent kinase 2 (CDK2) inactivation, which overcomes the differentiation arrest of acute myeloid leukemia (AML) cells, may be a promising method for AML treatment. However, there is no available selective CDK2 inhibitor. More importantly, the inhibition of only the enzymatic function of CDK2 would be insufficient to promote notable AML differentiation. To further validate the role and druggability of CDK2 involved in AML differentiation, a suitable chemical tool is needed. Therefore, we developed first-in-class CDK2-targeted proteolysis-targeting chimeras (PROTACs), which promoted rapid and potent CDK2 degradation in different cell lines without comparable degradation of other targets, and induced remarkable differentiation of AML cell lines and primary patient cells. These data clearly demonstrated the practicality and importance of PROTACs as alternative tools for verifying CDK2 protein functions.

This paper reports environment-friendly fiberboard with high mechanical strength using delignified wood fibers and chitosan adhesive. The influence of delignification on chemical structure and microstructure of wood fibers and mechanical strength and water resistance of fiberboards was studied. The results showed delignification effectively removed hemicellulose and a part of lignin, decomposed some large-sized lignin into small fragments distributed on wood fiber surface, and exposed cellulose bundles. The mechanical strength and water resistance of fiberboards using wood fibers delignified for 3 h reached optimal and were far higher than the requirement of the Chinese national standard. The large improvement in internal bonding strength (IB) and thickness swell (24 h TS) was mainly attributed to the delignification, while that in modulus of rupture (MOR) and modulus of elasticity (MOE) was principally due to the addition of chitosan adhesive. This study can open a new path for production of scalable environment-friendly high-performance wooden composite.

We find that deviations from the covered interest rate parity (CIP) condition imply large, persistent, and systematic arbitrage opportunities in one of the largest asset markets in the world. Contrary to the common view, these deviations for major currencies are not explained away by credit risk or transaction costs. They are particularly strong for forward contracts that appear on banks' balance sheets at the end of the quarter, pointing to a causal effect of banking regulation on asset prices. The CIP deviations also appear significantly correlated with other fixed income spreads and with nominal interest rates.