In situ Nanoindentation Study of Plastic Co-deformation in Al-TiN Nanocomposites

Abstract

We performed in situ indentation in a transmission electron microscope on Al-TiN multilayers with individual layer thicknesses of 50 nm, 5 nm and 2.7 nm to explore the effect of length scales on the plastic co-deformability of a metal and a ceramic. At 50 nm, plasticity was confined to the Al layers with easy initiation of cracks in the TiN layers. At 5 nm and below, cracking in TiN was suppressed and post mortem measurements indicated a reduction in layer thickness in both layers. The results demonstrate the profound size effect in enhancing plastic co-deformability in nanoscale metal-ceramic multilayers.

Linking BRCA1 to NAD World

“…[3][4][5][6] Nicotinamide adenine dinucleotide (NAD), as well as its precursors, derivatives, and metabolic enzymes, has recently drawn much attention as regards a variety of biological functions including transcriptional regulation, DNA repair, cell cycle progression, metabolism, lifespan, and cell death. 7 Typically, (i) sirtuin 1 (SIRT1) is an NAD-dependent protein deacetylase; (ii) poly(ADP-ribose) polymerase-1 (PARP1) as a sensor of DNA damage catalyzes the transfer of ADPribose units from NAD to target proteins; (iii) nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis, which together comprise a system of regulatory networks, termed the 'NAD World', that maintains the balance of cellular metabolism and has essential roles in tumor development and therapy.…”

“…For example, (i) BRCA1 is responsible for NAMPT-mediated NAD synthesis, and NAD can feedback-activate BRCA1 expression; 6 (ii) NAD serves as the common substrate independent of its redoxcarrier function by SIRT1 and PARP1; 3,5 (iii) BRCA1 is an important modulator of cellular stresses such as metabolic stress, oxidative stress, and replication stress. Similarly, SIRT1 is a key metabolic sensor in response to cellular stress; 5 (iv) BRCA1 is a positive regulator for PARP1 levels and NAD-dependent PARP1 activity, and the high efficiency of PARP1-mediated NAD consumption can feedback inhibit BRCA1 transcription; 3 (v) BRCA1 has been shown to serve as a positive regulator of SIRT1 by binding to the promoter regiondecreased levels of SIRT1 are triggered by BRCA1 inactivation, and may reduce the intracellular NAD consumption, which plays a partial role in the elevated NAD levels. 6 Therefore, the emerging picture from these studies prompted us to evaluate a possible link between BRCA1 and NAD World.…”

“…SIRT1 can positively regulate autophagy under oxidative stress. In this regard, SIRT1 expression and imbalance in its activity may be involved in BRCA1-related oxidative stress and autophagy; 5 (iii) Endoplasmic reticulum (ER) stress signaling plays an important part in the induction of BRCA1 expression. However, ER stress can be attenuated by a SIRT1-dependent mechanism.…”

“…Therefore, BRCA1-related elevated levels of SIRT1 may resist the adverse effects of ER stress. 5 As summarized in Fig. 1, proposed model of the role of BRCA1 in the regulation of SIRT1 and PARP1.…”

High Numerical Aperture Epi-illumination Selective Plane Illumination Microscopy

“…To accommodate traditional mounting protocols such as samples prepared on glass coverslips, "dipping" configurations 3,4 were developed, with perpendicular optical pathways and the objectives pointing downwards. On the other hand, an "open-top" configuration with the objectives pointing upwards [5][6][7] potentially allows a SPIM system to be operated like an inverted fluorescence microscope and accept conventional biological sample formats including multi-well plates. Among such methods, Oblique Illumination Microscopy 8 and Swept Confocally Aligned Planar-Excitation microscopy (SCAPE) 9 use a single objective lens for illumination and detection without additional reflecting elements [10][11][12] in the sample space.…”