On the Thermal Activation of Negative Bias Temperature Instability

The temperature dependence of negative bias temperature instability (NBTI) is investigated on 2.0nm SiO2 devices from temperatures ranging from 300K down to 6K with a measurement window of ~12ms to 100s. Results indicate that classic NBTI degradation is observed down to ~200K and rarely observed at temperatures below 140K in the experimental window. Since experimental results show the charge trapping component contributing to NBTI is thermally activated, the results cannot be explained with the conventionally employed elastic tunneling theory. A new mechanism is observed at temperatures below 200K where device performance during stress conditions improves rather than degrades with time, which is opposite to the classical NBTI phenomenon

A novel link between the proteasome pathway and the signal transduction pathway of the Bone Morphogenetic Proteins (BMPs)

BACKGROUND: The intracellular signaling events of the Bone Morphogenetic Proteins (BMPs) involve the R-Smad family members Smad1, Smad5, Smad8 and the Co-Smad, Smad4. Smads are currently considered to be DNA-binding transcriptional modulators and shown to recruit the master transcriptional co-activator CBP/p300 for transcriptional activation. SNIP1 is a recently discovered novel repressor of CBP/p300. Currently, the detailed molecular mechanisms that allow R-Smads and Co-Smad to co-operatively modulate transcription events are not fully understood. RESULTS: Here we report a novel physical and functional link between Smad1 and the 26S proteasome that contributes to Smad1- and Smad4-mediated transcriptional regulation. Smad1 forms a complex with a proteasome β subunit HsN3 and the ornithine decarboxylase antizyme (Az). The interaction is enhanced upon BMP type I receptor activation and occur prior to the incorporation of HsN3 into the mature 20S proteasome. Furthermore, BMPs trigger the translocation of Smad1, HsN3 and Az into the nucleus, where the novel CBP/p300 repressor protein SNIP1 is further recruited to Smad1/HsN3/Az complex and degraded in a Smad1-, Smad4- and Az-dependent fashion. The degradation of the CBP/p300 repressor SNIP1 is likely an essential step for Smad1-, Smad4-mediated transcriptional activation, since increased SNIP1 expression inhibits BMP-induced gene responses. CONCLUSIONS: Our studies thus add two additional important functional partners of Smad1 into the signaling web of BMPs and also suggest a novel mechanism for Smad1 and Smad4 to co-modulate transcription via regulating proteasomal degradation of CBP/p300 repressor SNIP1

Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK ). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation

La gestion des compétences à l'épreuve de la compétence collective

Ce chapitre a pour objet d'analyser la visibilité de la compétence collective à travers les outils de gestion. Dans un premier point, il identifie comment la compétence collective est prise en compte théoriquement et empiriquement. Cette réflexion préliminaire permet de montrer, dans un deuxième point, le caractère contradictoire de la gestion des compétences qui fait émerger la compétence collective tout en renforçant la prise en compte de l'individu. Cette contradiction se retrouve également dans la construction et l'usage des référentiels comme le montre le troisième point qui souligne à la fois la difficulté de prise en compte de la dimension collective de la compétence dans l'évaluation des salariés et l'orientation de ces outils vers l'évaluation des comportements