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"Joyce, Michael"
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Heavy-duty trucks
\"Describes different kinds of trucks and explains what they do\"--Provided by publisher.
Book
QE and the Gilt Market: a Disaggregated Analysis
We examine the impact of the first phase of the Bank of England's quantitative easing (QE) programme during March 2009—January 2010 on the UK government bond (gilt) market, using high-frequency, disaggregated data on individual gilts. We find that: QE announcements took varying amounts of time to get incorporated into market prices and had significant effects on the shape of the term structure; the Bank's reverse auctions were initially associated with additional yield reductions; and, allowing for fiscal news and the changing macroeconomic outlook, QE appears to have had persistent effects on gilt yields.
Journal Article
Quantitative Easing and Unconventional Monetary Policy - an Introduction
This article assesses the impact of Quantitative Easing and other unconventional monetary policies followed by central banks in the wake of the financial crisis that began in 2007. We consider the implications of theoretical models for the effectiveness of asset purchases and look at the evidence from a range of empirical studies. We also provide an overview of the contributions of the other articles in this Feature.
Journal Article
The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites
Hepatitis C virus (HCV) is a positive-strand RNA virus of the Flaviviridae family and a major cause of liver disease worldwide. HCV replicates in the cytoplasm, and the synthesis of viral proteins induces extensive rearrangements of host cell membranes producing structures, collectively termed the membranous web (MW). The MW contains the sites of viral replication and assembly, and we have identified distinct membrane fractions derived from HCV-infected cells that contain replication and assembly complexes enriched for viral RNA and infectious virus, respectively. The complex membrane structure of the MW is thought to protect the viral genome limiting its interactions with cytoplasmic pattern recognition receptors (PRRs) and thereby preventing activation of cellular innate immune responses. Here we show that PRRs, including RIG-I and MDA5, and ribosomes are excluded from viral replication and assembly centers within the MW. Furthermore, we present evidence that components of the nuclear transport machinery regulate access of proteins to MW compartments. We show that the restricted assess of RIG-I to the MW can be overcome by the addition of a nuclear localization signal sequence, and that expression of a NLS-RIG-I construct leads to increased immune activation and the inhibition of viral replication.
Journal Article
الكذاب..! وقصص حديثة أخرى = Liar! and other modern stories : قصص للشباب
\"الكذاب..! وقصص حديثة أخرى: قصص للشباب\" هو كتاب يضم مجموعة من القصص القصيرة، من تأليف إسحاق أزيموف وستة كتاب آخرين، وترجمة مها فرزات البني، يتضمن الكتاب مجموعة من القصص التي تستهدف فئة الشباب، وتتنوع بين الخيال العلمي والمغامرة والتشويق، القصص تحمل في طياتها رسائل وقيم تهدف إلى تنمية التفكير النقدي والإبداعي لدى الشباب، هذه القصة تعتبر من أبرز القصص في الكتاب. كتبها إسحاق أزيموف، وتدور حول روبوت يتمتع بقدرة فريدة على الكذب، مما يؤدي إلى سلسلة من الأحداث المثيرة التي تستكشف طبيعة الحقيقة والكذب والتداعيات الأخلاقية للتكنولوجيا المتقدمة.
Book
Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication
The main protease, M
pro
(or 3CL
pro
) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide. Feline infectious peritonitis, a fatal coronavirus infection in cats, was successfully treated previously with a prodrug GC376, a dipeptide-based protease inhibitor. Here, we show the prodrug and its parent GC373, are effective inhibitors of the M
pro
from both SARS-CoV and SARS-CoV-2 with IC
50
values in the nanomolar range. Crystal structures of SARS-CoV-2 M
pro
with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 replication in cell culture. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals. The work here lays the framework for their use in human trials for the treatment of COVID-19.
Coronavirus main protease is essential for viral polyprotein processing and replication. Here Vuong et al. report efficient inhibition of SARS-CoV-2 replication by the dipeptide-based protease inhibitor GC376 and its parent GC373, which were originally used to treat feline coronavirus infection.
Journal Article
Institutional Investors and the QE Portfolio Balance Channel
The operation of the portfolio balance channel has been emphasized by monetary policymakers as a key channel through which quantitative easing (QE) policies work. We assess whether the investment behavior of insurance companies and pension funds in the United Kingdom during the global financial crisis was consistent with such an effect by analyzing both sectoral and institution-level data. Our results suggest QE led to institutional investors shifting their portfolios away from government bonds toward corporate bonds but did not lead to a shift into equities.
Journal Article
HCV and flaviviruses hijack cellular mechanisms for nuclear STAT2 degradation: Up-regulation of PDLIM2 suppresses the innate immune response
Host encounters with viruses lead to an innate immune response that must be rapid and broadly targeted but also tightly regulated to avoid the detrimental effects of unregulated interferon expression. Viral stimulation of host negative regulatory mechanisms is an alternate method of suppressing the host innate immune response. We examined three key mediators of the innate immune response: NF-KB, STAT1 and STAT2 during HCV infection in order to investigate the paradoxical induction of an innate immune response by HCV despite a multitude of mechanisms combating the host response. During infection, we find that all three are repressed only in HCV infected cells but not in uninfected bystander cells, both in vivo in chimeric mouse livers and in cultured Huh7.5 cells after IFNα treatment. We show here that HCV and Flaviviruses suppress the innate immune response by upregulation of PDLIM2, independent of the host interferon response. We show PDLIM2 is an E3 ubiquitin ligase that also acts to stimulate nuclear degradation of STAT2. Interferon dependent relocalization of STAT1/2 to the nucleus leads to PDLIM2 ubiquitination of STAT2 but not STAT1 and the proteasome-dependent degradation of STAT2, predominantly within the nucleus. CRISPR/Cas9 knockout of PDLIM2 results in increased levels of STAT2 following IFNα treatment, retention of STAT2 within the nucleus of HCV infected cells after IFNα stimulation, increased interferon response, and increased resistance to infection by several flaviviruses, indicating that PDLIM2 is a global regulator of the interferon response.
Journal Article