The role of EF-hand in calmodulin binding of voltage-gated Cav2.1 and Cav2.2 calcium channels

Voltage-gated Cav2.1 (P/Q-type) and Cav2.2 (N-type) channels are two closely related calcium channels that play indispensable roles in signal transduction pathways by regulating neurotransmitter release. Despite having highly conserved amino acid sequences, they are differentially modulated by calmodulin, which mediate two important feedback mechanisms known as Ca2+-dependent inactivation (CDI) and Ca2+-dependent facilitation (CDF). These dual regulatory mechanisms contribute to synaptic plasticity, but only CDI is observed in Cav2.2 channel, while both CDI and CDF are present in Cav2.1 channel. Previously, it was hypothesized that the lack of CDF in Cav2.2 channel is due to the pre-IQ-IQ domain of the channel’s lower binding affinity for calmodulin compared to that of Cav2.1 channel. Now that the EF-hand domain of calcium channels is identified as one of the two minimally required molecular determinants that are responsible for supporting CDF in Cav2.1 channel and preventing CDF in Cav2.2 channel, it was necessary to determine the role of EF-hand domain in calmodulin binding of Cav2.1 and Cav2.2 channels. Using pull-down binding assays, this study finds that the EF-hand domain enhances calmodulin binding to the proximal C-terminal domain of Cav2.2 channel, which suggests that the lack of CDF in Cav2.2 does not result from the channel’s weak interaction with CaM, but from the EF-pre-IQ-IQ domain of the channel’s inability to allow calmodulin from fully exerting its effects

Label-free quantum super-resolution imaging using entangled multi-mode squeezed light

In this study, we explore the theoretical application of entangled multi-mode squeezed light for label-free optical super-resolution imaging. By generating massively entangled multi-mode squeezed light through an array of balanced beam splitters, using a single-mode squeezed light input, we create a multi-mode quantum light state with exceptional entanglement and noise suppression below the shot noise level. This significantly reduces imaging measurement errors compared to classical coherent state light imaging when the same number of photons are used on the imaging sample. We demonstrate how to optimize the imaging system's parameters to achieve the Heisenberg imaging error limit, taking into account the number of entangled modes and photons used. We also examine the effects of optical losses in the imaging system, necessitating adjustments to the optimized parameters based on the degree of optical loss. In practical applications, this new quantum imaging approach reduces the number of photons needed to achieve the same image quality by two orders of magnitude compared to classical imaging methods that use non-entangled, non-squeezed coherent state light

Fundamental limits to the generation of highly displaced bright squeezed light using linear optics and parametric amplifiers

High quality squeezed light is an important resource for a variety of applications. Multiple methods for generating squeezed light are known, having been demonstrated theoretically and experimentally. However, the effectiveness of these methods -- in particular, the inherent limitations to the signals that can be produced -- has received little consideration. Here we present a comparative theoretical analysis for generating a highly-displaced high-brightness squeezed light from a linear optical method -- a beam-splitter mixing a squeezed vacuum and a strong coherent state -- and parametric amplification methods including an optical parametric oscillator, an optical parametric amplifier, and a dissipative optomechanical squeezer seeded with coherent states. We show that the quality of highly-displaced high-brightness squeeze states that can be generated using these methods is limited on a fundamental level by the physical mechanism utilized; across all methods there are significant tradeoffs between brightness, squeezing, and overall uncertainty. We explore the nature and extent of these tradeoffs specific to each mechanism and identify the optimal operation modes for each, and provide an argument for why this type of tradeoff is unavoidable for parametric amplifier type squeezers

Qualitative analysis of Request For Information to identify design flaws in steel construction projects

Request for information (RFI) is a formal process used in the Architecture, Engineering and Construction industry to address design flaws that affect communication between designers and contractors. A large number of RFIs are a sign of a lack of precision or coordination in the design documents. However, RFIs produce rich, precise, and structured information. Analyzing their content can help to identify recurring problems between designers and construction teams and better tailor future projects to the working context of the contractors. This article presents a method for identifying recurring issues during the design phase of steel construction projects through the analysis of the contents of RFIs. It is original in using a qualitative content analysis tool that can analyze large quantities of RFIs rapidly. Identifying the recurrent problems of contractors will allow the establishment of rules to be taken into consideration during the design phase of future steel construction projects. A case study of 26 steel construction projects demonstrates the feasibility of this method. This case study shows that, given the same designers and construction teams, recurring problems shown in RFIs do not differ according to the scale of the projects. In this case, the main issue between designers and contractors is the lack and inadequate presentation of information related to the connection of steel components. Identifying these problems can pave the way for initiatives to improve the design phase and can be an essential step in making contractors’ knowledge available to designers early in the projects