BTK inhibition sensitizes acute lymphoblastic leukemia to asparaginase by suppressing the amino acid response pathway

Asparaginase (ASNase) therapy has been a mainstay of acute lymphoblastic leukemia (ALL) protocols for decades and shows promise in the treatment of a variety of other cancers. To improve the efficacy of ASNase treatment, we used a CRISPR/Cas9-based screen to identify actionable signaling intermediates that improve the response to ASNase. Both genetic inactivation of Bruton’s tyrosine kinase (BTK) and pharmacological inhibition by the BTK inhibitor ibrutinib strongly synergize with ASNase by inhibiting the amino acid response pathway, a mechanism involving c-Myc–mediated suppression of GCN2 activity. This synthetic lethal interaction was observed in 90% of patient-derived xenografts, regardless of the genomic subtype. Moreover, ibrutinib substantially improved ASNase treatment response in a murine PDX model. Hence, ibrutinib may be used to enhance the clinical efficacy of ASNase in ALL. This trial was registered at www.clinicaltrials.gov as # NCT02884453

Determinants of Foreign Direct Investment

Using a dataset which breaks down FDI flows into primary, secondary and tertiary sector investments and a GMM dynamic approach to address concerns about endogeneity, the paper analyzes various macroeconomic, developmental, and institutional/qualitative determinants of FDI in a sample of emerging market and developed economies. While FDI flows into the primary sector show little dependence on any of these variables, secondary and tertiary sector investments are affected in different ways by countries’ income levels and exchange rate valuation, as well as development indicators such as financial depth and school enrollment, and institutional factors such as judicial independence and labor market flexibility. Finally, we find that the effect of these factors often differs between advanced and emerging economies.Foreign direct investment;Developing countries;Economic models;Emerging markets;Gross domestic product;fdi, direct investment, investors, investment decisions, host country, foreign investment, foreign companies, foreign investors, macroeconomic stability, host countries, international finance, institutional development, international investors, investment flows, international investment, market size, international trade, multinational enterprise, host economy, foreign markets, direct foreign investment, foreign technology, manufacturing direct foreign investment, investment location decisions, multinational enterprises, regulatory framework, multinational firms, global capital

Construction of Multishelled Binary Metal Oxides via Coabsorption of Positive and Negative Ions as a Superior Cathode for Sodium-Ion Batteries

Multishelled binary metal oxide, which can exert a synergetic effect of different oxides, is a promising electrochemical electrode material. However, it is challenging to synthesize this kind of binary metal oxide due to the severe hydrolysis and/or precipitation reactions of the precursors between cations and anions of different metals. Herein, by using citric acid as a chelating agent to inhibit hydrolysis and precipitation, a series of multishelled binary metal oxide hollow spheres (Fe-2(MoO4)(3), NiMoO4, MnMoO4, CoWO4, MnWO4, etc.) were obtained via coabsorption of negative and positive metal ions. In addition, the chelation between a metal ion and citric acid is systematically validated by NMR, MS, Raman, and UV-vis. In particular, multishelled Fe-2(MoO4)(3) hollow spheres show excellent electrochemical performance as cathode material for sodium-ion batteries benefited from their structural superiorities. Especially, the quintuple-shelled Fe-2(MoO4)(3) hollow sphere shows the highest specific capacity (99.03 mAh g(-1)) among all Fe-2(MoO4)(3) hollow spheres, excellent stability (85.6 mAh g(-1) was retained after 100 cycles at a current density of 2.2 C), and outstanding rate capability (67.4 mAh g(-1) can be obtained at a current density of 10 C). This general approach can be extended to the synthesis of other multishelled multielement metal oxides and greatly enrich the diversity of hollow multishelled structures

FIGURE 3. Allokepon longicauda n in A new species and two new record species of genus Allokepon Markham, 1982 (Isopoda: Epicaridea: Bopyridae) from China

FIGURE 3. Allokepon longicauda n. sp. Female (A–F). A, dorsal view. B, ventral view. C, right maxilliped, external view. D, Barbula, right side. E, right oostegite 1, external view. F, right oostegite 1, internal view. G, left pereopod 7. Male (H, I). H, dorsal view. I, ventral view. Scale 1.00 mm for A, B; 0.42 mm for C, D, E, F; 0.25 mm for G, H, I

Financing Infrastructure in India

Driving infrastructure development, notably mobilizing financial resources for infrastructure projects, has been challenging in many countries. This study includes two parts: an empirical analysis of macroeconomic risks associated with infrastructure booms, and a case study of four emerging economies about their practice of funding infrastructure development. The study shows that (i) there is no empirical evidence that rapid infrastructure growth would undermine contemporary macroeconomic performance, implying that room is created to accommodate infrastructure booms without compromising fiscal and external sustainability; (ii) banks may play an important role in financing infrastructure, but caution is needed to avoid directed lending and regulatory forbearance that the authorities may use to promote financing; (iii) capital market development is important to accommodate the usually high financing needs, and encouraging private investors to move into infrastructure would require regulatory and institutional improvements; and (iv) public support, including credit guarantees, may help bolster investors'' confidence, but the authorities should carefully monitor and manage fiscal risks.Economic growth;Electric power;Emerging markets;Public investment;Transport;bonds, investors, bond, bond market, stock market, commercial banks, infrastructure bonds, private capital, financial sector, institutional investors, private investment, corporate bond, corporate bond market, financial system, foreign investors, crowding out, foreign currency, foreign companies, gross fixed capital formation, financial markets, fixed income, fixed capital, stock exchange, cost of capital, credit guarantees, bond markets, bond insurance, minority shareholders, financial institutions, domestic bonds, foreign equity, private equity, reserve requirements, guarantee funds, retained earnings, minority shareholdings, minimum revenue guarantees, coupon rate, present value, corporate bonds, bond funds, domestic bond, yankee bond, international banks, yankee bonds, foreign bonds, domestic investment, derivatives markets, interest rate derivatives, commercial basis, foreign investment, financial assets, convertible bonds, investment spending, foreign capital, net present value, bond issuance, stock market capitalization, original maturity, direct investment, investment fund, domestic financial sector, private placement, trade credit, foreign direct investment, local bond markets, investment needs, credit markets, investment promotion, local bond, currency risk, working capital loans, financial instruments, hedging, investment promotion law, financial resources, regulatory framework

Decoding lithium batteries through advanced in situ characterization techniques

Given the energy demands of the electromobility market, the energy density and safety of lithium batteries (LBs) need to be improved, whereas its cost needs to be decreased. For the enhanced performance and decreased cost, more suitable electrode and electrolyte materials should be developed based on the improved understanding of the degradation mechanisms and structure-performance correlation in the LB system. Thus, various in situ characterization technologies have been developed during the past decades, providing abundant guidelines on the design of electrode and electrolyte materials. Here we first review the progress of in situ characterization of LBs and emphasize the feature of the multi-model coupling of different characterization techniques. Then, we systematically discuss how in situ characterization technologies reveal the electrochemical processes and fundamental mechanisms of different electrode systems based on representative electrode materials and electrolyte components. Finally, we discuss the current challenges, future opportunities, and possible directions to promote in situ characterization technologies for further improvement of the battery performance

Hollow Nanostructures for Surface/Interface Chemical Energy Storage Application

Hollow nanostructures garner tremendous interest in the area of energy conversion and storage, owning to its large surface area, facilitated transport path and good buffering capability. In this paper, we summarize the recent research on hollow nanostructures with controllable structure and morphology for surface/interface chemical energy storage. First, we introduce the charge storage mechanism and challenges of surface/interface chemical energy storage, mainly including supercapacitor. Subsequently, we discuss the influence of structure parameters of hollow nanostructures on the performance of surface/interface chemical energy storage device in detail. Afterwards, we systematically outline the recent applications of hollow nanostructures as electrode materials for supercapacitors. By adopting hollow nanostructures, the specific capacitance, cycle stability and rate capability of supercapacitors can be greatly improved. Finally, the emergent challenges and future development directions in hollow nanostructures for surface/interface chemical energy storage are provided