MICROSTRUCTURAL IMPACT ON ELECTROMIGRATION: A TCAD STUDY

Current electromigration models used for simulation and analysis of interconnect reliability lack the appropriate description of metal microstructure and consequently have a very limited predictive capability. Therefore, the main objective of our work was obtaining more sop histicated electromigration models. The problem is addressed through a combination of different levels of atomistic modeling and already available continuum level macroscopic models. A novel method for an ab initio calculation  of the effective valence for electromigration is presented and its application on the analysis of EM behavior is demonstrated. Additionally, a simple analytical model for the early electromigration lifetime is obtained. We have shown that itsapplication gives a reasonable estimate for the early electromigration failuresincluding the effect of microstructure

Mechanism of completion of peptidyltransferase centre assembly in eukaryotes.

During their final maturation in the cytoplasm, pre-60S ribosomal particles are converted to translation-competent large ribosomal subunits. Here, we present the mechanism of peptidyltransferase centre (PTC) completion that explains how integration of the last ribosomal proteins is coupled to release of the nuclear export adaptor Nmd3. Single-particle cryo-EM reveals that eL40 recruitment stabilises helix 89 to form the uL16 binding site. The loading of uL16 unhooks helix 38 from Nmd3 to adopt its mature conformation. In turn, partial retraction of the L1 stalk is coupled to a conformational switch in Nmd3 that allows the uL16 P-site loop to fully accommodate into the PTC where it competes with Nmd3 for an overlapping binding site (base A2971). Our data reveal how the central functional site of the ribosome is sculpted and suggest how the formation of translation-competent 60S subunits is disrupted in leukaemia-associated ribosomopathies.Bloodwise, MRC, Wellcome Trus

Electromigration reliability of open TSV structures

a b s t r a c t Through silicon vias are the components in three-dimensional integrated circuits, which are responsible for the vertical connection inside the dies. In this work we present studies about the reliability of open through silicon vias against electromigration. A two-step approach is followed. In the first step the stress development of a void free structure is analysed by means of simulation to find the locations, where voids due to stress are most probably nucleated. In the second step, voids are placed in the through silicon vias and their evolution is traced including the increase of resistance. The resistance raises more than linearly in time and shows an abrupt open circuit failure. These results are in good agreement with results of time accelerated electromigration tests

Hepatic Stellate Cell Activation and Inactivation in NASH-Fibrosis—Roles as Putative Treatment Targets?

Hepatic fibrosis is the primary predictor of mortality in patients with non-alcoholic steatohepatitis (NASH). In this process, the activated hepatic stellate cells (HSCs) constitute the principal cells responsible for the deposition of a fibrous extracellular matrix, thereby driving the hepatic scarring. HSC activation, migration, and proliferation are controlled by a complex signaling network involving growth factors, lipotoxicity, inflammation, and cellular stress. Conversely, the clearance of activated HSCs is a prerequisite for the resolution of the extracellular fibrosis. Hence, pathways regulating the fate of the HSCs may represent attractive therapeutic targets for the treatment and prevention of NASH-associated hepatic fibrosis. However, the development of anti-fibrotic drugs for NASH patients has not yet resulted in clinically approved therapeutics, underscoring the complex biology and challenges involved when targeting the intricate cellular signaling mechanisms. This narrative review investigated the mechanisms of activation and inactivation of HSCs with a focus on NASH-associated hepatic fibrosis. Presenting an updated overview, this review highlights key cellular pathways with potential value for the development of future treatment modalities