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John Sinclair is one of the major figures in applied linguistics and his work is essential study for students. This accessible book collects in one volume Sinclair's key papers on written discourse structure, lexis patterns, phraseology, corpus analysis, lexicography and linguistic theory from the 1990s. All the papers have been edited and updated for this book. The clear and accessible introduction helps students to navigate his key themes and arguments, making the volume an ideal companion for those coming to Sinclair's more recent writings for the first time.
' ... the book contains valuable insights from which both discourse analysts and corpus linguistics will benefit.' - BaaL News
eBook
HCMV Antivirals and Strategies to Target the Latent Reservoir
Human cytomegalovirus (HCMV) is a ubiquitous human herpesvirus. In healthy people, primary infection is generally asymptomatic, and the virus can go on to establish lifelong latency in cells of the myeloid lineage. However, HCMV often causes severe disease in the immunosuppressed: transplant recipients and people living with AIDS, and also in the immunonaive foetus. At present, there are several antiviral drugs licensed to control HCMV disease. However, these are all faced with problems of poor bioavailability, toxicity and rapidly emerging viral resistance. Furthermore, none of them are capable of fully clearing the virus from the host, as they do not target latent infection. Consequently, reactivation from latency is a significant source of disease, and there remains an unmet need for treatments that also target latent infection. This review briefly summarises the most common HCMV antivirals used in clinic at present and discusses current research into targeting the latent HCMV reservoir.
Journal Article
Action Comics #1000
\"Action Comics #1 gave birth to America's greatest superhero, Superman. Now celebrate 1,000 issues of Action Comics with this collector's item hardcover, including an all-star lineup of writers and artists such as Brian Michael Bendis, Geoff Johns, Tom King, Brad Meltzer, Scott Snyder, Jim Lee, John Cassaday, Olivier Coipel, and an unpublished story from Marv Wolfman and ... Man of Steel artist Curt Swan, plus more\"-- Provided by publisher.
Book
Design and Conduct Considerations for First‐in‐Human Trials
A milestone step in translational science to transform basic scientific discoveries into therapeutic applications is the advancement of a drug candidate from preclinical studies to initial human testing. First‐in‐human (FIH) trials serve as the link to advance new promising drug candidates and are conducted primarily to determine the safe dose range for further clinical development. Cross‐functional collaboration is essential to ensure efficient and successful FIH trials. The aim of this publication is to serve as a tutorial for conducting FIH trials for both small molecule and biological drug candidates with topics covering regulatory requirements, preclinical safety testing, study design considerations, safety monitoring, biomarker assessment, and global considerations. An emphasis is placed on FIH trial design considerations, including starting dose selection, study size and population, dose escalation scheme, and implementation of adaptive designs. In light of the recent revision of the European Medicines Agency (EMA) guideline on FIH trials to promote safety and mitigate risk, we also discuss new measures introduced in the guideline that impact FIH trial design.
Journal Article
The Flash by Geoff Johns. Book one
\"When the Flash breaks through space and time to reach a parallel Earth, it mirrors our own, except for one big difference--there is no Speed Force. Disconnected from the energy source that powers all super-speedsters, this is a world where the Flash never existed and one that has become deadly for anyone who wears a mask. Powerless and hunted by the law, the only way Wally West can survive and escape is to accept help from those he trusts the least--his own Rogues Gallery\"--Page 4 of cover.
Book
The Human Cytomegalovirus β2.7 Long Non-Coding RNA Prevents Induction of Reactive Oxygen Species to Maintain Viral Gene Silencing during Latency
Human cytomegalovirus (HCMV) is a significant source of disease for the immunosuppressed and immunonaive. The treatment of HCMV is made more problematic by viral latency, a lifecycle stage in which the virus reduces its own gene expression and produces no infectious virus. The most highly expressed viral gene during HCMV latency is the viral β2.7 long non-coding RNA. Although we have recently shown that the β2.7 lncRNA lowers levels of reactive oxygen species (ROS) during infection in monocytes, how this impacts latency is unclear. We now show that β2.7 is important for establishing and maintaining HCMV latency by aiding the suppression of viral lytic gene expression and that this is directly related to its ability to quench reactive oxygen species (ROS). Consistent with this, we also find that exogenous inducers of ROS cause reactivation of latent HCMV. These effects can be compensated by treatment with an antioxidant to lower ROS levels. Finally, we show that ROS-mediated reactivation is independent of myeloid differentiation, but instead relies on NF-κB activation. Altogether, these results reveal a novel factor that is central to the complex process that underpins HCMV latency. These findings may be of particular relevance in the transplant setting, in which transplanted tissue/organs are subject to very high ROS levels, and HCMV reactivation poses a significant threat.
Journal Article