GS-9822, a preclinical LEDGIN candidate, displays a block-and-lock phenotype in cell culture. [PDF]
Antimicrob Agents Chemother, 2023 The ability of HIV to integrate into the host genome and establish latent reservoirs is the main hurdle preventing an HIV cure. LEDGINs are small-molecule integrase inhibitors that target the binding pocket of LEDGF/p75, a cellular cofactor that substantially contributes to HIV integration site selection.
Bruggemans A +6 more
europepmc +5 more sources
Shock-and-kill versus block-and-lock: Targeting the fluctuating and heterogeneous HIV-1 gene expression. [PDF]
Proc Natl Acad Sci U S A, 2021 Despite effective antiretroviral therapy, HIV-1 persistence in the latent reservoir remains the major barrier to cure. Current strategies for HIV-1 eradication require either inducing HIV-1 expression to expose latently infected cells for immune clearance [known as the “shock-and-kill strategy” (1)] or silencing HIV-1 expression for a prolonged drug ...
Yeh YJ, Ho YC.
europepmc +4 more sources
New latency-promoting agents for a block-and-lock functional cure strategy. [PDF]
Curr Opin HIV AIDSPurpose of review Currently, HIV-infected patients are treated with antiretroviral therapy. However, when the treatment is interrupted, viral rebound occurs from latently infected cells. Therefore, scientists aim to develop an HIV-1 cure which eradicates or permanently silences the latent reservoir.
Pellaers E, Denis A, Debyser Z.
europepmc +3 more sources
Block-and-Lock Approaches for HIV Cure: Mechanistic Insights, Challenges, and Emerging Role of CPSF6. [PDF]
Int J Mol SciThe block-and-lock strategy aims to achieve a functional cure for human immunodeficiency virus type 1 (HIV-1) infection by enforcing durable, drug-independent silencing of proviral transcription. Several latency-promoting agents have been described that effectively limit viral reactivation in vitro or in animal models.
Tolomeo M, Cascio A.
europepmc +2 more sources
Torsion–Shear Behaviour at Interlocking Joints: Calibration of Discrete Element-Deformable Models Using Experimental and Numerical Analyses [PDF]
, 2023 An interlocking block is a concave polyhedron with non-planar joints connecting the blocks together. The possibility of the fracture within a masonry interlocking block is a major challenge that has remained rather unexplored yet.
Casapulla C., Mousavian E., Bagi K.
core +2 more sources
Towards a Functional Cure of HIV-1: Insight Into the Chromatin Landscape of the Provirus
Frontiers in Microbiology, 2021 Despite potent combination antiretroviral therapy, HIV-1 infection persists due to irreversible integration of the virus in long-living cells of the immune system.
Julie Janssens +3 more
doaj +1 more source
An Overview of Charge Pump for Phase Lock Loop System for High Frequency Application. [PDF]
, 2020 Phase lock loop is fundamental buliding block of modern communication system. Phase lock loop are typically used to provide local oscillator function in radio reciver or transmitter.
JAISWAL, VISHAL D., Nasre, Vrushali G.
core +3 more sources
Parameterization of the ABS electronic control unit for increasing the autonomous trucks’ active safety [PDF]
MATEC Web of Conferences, 2021 The article is devoted to the issue of improving the autonomous vehicles safety. The anti-lock braking system was chosen as the object of the study, since it is one of the components of the vehicle active safety during emergency braking.
Begizhonov Shakhrom +3 more
doaj +1 more source
Forging a Functional Cure for HIV: Transcription Regulators and Inhibitors
Viruses, 2022 Current antiretroviral therapy (ART) increases the survival of HIV-infected individuals, yet it is not curative. The major barrier to finding a definitive cure for HIV is our inability to identify and eliminate long-lived cells containing the dormant ...
Sonia Mediouni +3 more
doaj +1 more source