Vector representation of resonators in eigencoupling state space and eigenloss state space of piezoelectric ceramics

The calculation of the vector representation of resonators in the coupling and loss eigenstate spaces is presented. The coupling and loss eigenstates are located in a Cartesian coordinate system, together with the vector representation of resonators. The convenience of this representation is illustrated by calculations of the coupling factor and the loss factor in an octant of space in which resonators are positioned

KA1-targeted regulatory domain mutations activate Chk1 in the absence of DNA damage

The Chk1 protein kinase is activated in response to DNA damage through ATR-mediated phosphorylation at multiple serine-glutamine (SQ) residues within the C-terminal regulatory domain, however the molecular mechanism is not understood. Modelling indicates a high probability that this region of Chk1 contains a kinase-associated 1 (KA1) domain, a small, compact protein fold found in multiple protein kinases including SOS2, AMPK and MARK3. We introduced mutations into Chk1 designed to disrupt specific structural elements of the predicted KA1 domain. Remarkably, six of seven Chk1 KA1 mutants exhibit constitutive biological activity (Chk1-CA) in the absence of DNA damage, profoundly arresting cells in G2 phase of the cell cycle. Cell cycle arrest induced by selected Chk1-CA mutants depends on kinase catalytic activity, which is increased several-fold compared to wild-type, however phosphorylation of the key ATR regulatory site serine 345 (S345) is not required. Thus, mutations targeting the putative Chk1 KA1 domain confer constitutive biological activity by circumventing the need for ATR-mediated positive regulatory phosphorylation

Does d-cycloserine facilitate the effects of homework compliance on social anxiety symptom reduction?

BACKGROUND: Prior studies examining the effect of d-cycloserine (DCS) on homework compliance and outcome in cognitive-behavior therapy (CBT) have yielded mixed results. The aim of this study was to investigate whether DCS facilitates the effects of homework compliance on symptom reduction in a large-scale study for social anxiety disorder (SAD). METHODS: 169 participants with generalized SAD received DCS or pill placebo during 12-session exposure-based group CBT. Improvements in social anxiety were assessed by independent raters at each session using the Liebowitz social anxiety scale (LSAS). RESULTS: Controlling for LSAS at the previous session, and irrespective of treatment condition, greater homework compliance in the week prior related to lower LSAS at the next session. However, DCS did not moderate the effect of homework compliance and LSAS, LSAS on homework compliance, or the overall augmenting effect of DCS on homework compliance. Furthermore, LSAS levels were not predictive of homework compliance in the following week. CONCLUSION: The findings support the general benefits of homework compliance on outcome, but not a DCS-augmenting effect. The comparably small number of DCS-enhanced sessions in this study could be one reason for the failure to find a facilitating effect of DCS

Enhancement of psychosocial treatment with D-cycloserine: models, moderators, and future directions

Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning).F31 MH103969 - NIMH NIH HHS; K24 DA030443 - NIDA NIH HHS; R34 MH099309 - NIMH NIH HHS; R34 MH086668 - NIMH NIH HHS; R21 MH102646 - NIMH NIH HHS; R34 MH099318 - NIMH NIH HH