Structural basis of effector regulation and signal termination in heterotrimeric Galpha proteins

This chapter addresses, from a molecular structural perspective gained from examination of x-ray crystallographic and biochemical data, the mechanisms by which GTP-bound Galpha subunits of heterotrimeric G proteins recognize and regulate effectors. The mechanism of GTP hydrolysis by Galpha and rate acceleration by GAPs are also considered. The effector recognition site in all Galpha homologues is formed almost entirely of the residues extending from the C-terminal half of alpha2 (Switch II) together with the alpha3 helix and its junction with the beta5 strand. Effector binding does not induce substantial changes in the structure of Galpha*GTP. Effectors are structurally diverse. Different effectors may recognize distinct subsets of effector-binding residues of the same Galpha protein. Specificity may also be conferred by differences in the main chain conformation of effector-binding regions of Galpha subunits. Several Galpha regulatory mechanisms are operative. In the regulation of GMP phospodiesterase, Galphat sequesters an inhibitory subunit. Galphas is an allosteric activator and inhibitor of adenylyl cyclase, and Galphai is an allosteric inhibitor. Galphaq does not appear to regulate GRK, but is rather sequestered by it. GTP hydrolysis terminates the signaling state of Galpha. The binding energy of GTP that is used to stabilize the Galpha:effector complex is dissipated in this reaction. Chemical steps of GTP hydrolysis, specifically, formation of a dissociative transition state, is rate limiting in Ras, a model G protein GTPase, even in the presence of a GAP; however, the energy of enzyme reorganization to produce a catalytically active conformation appears to be substantial. It is possible that the collapse of the switch regions, associated with Galpha deactivation, also encounters a kinetic barrier, and is coupled to product (Pi) release or an event preceding formation of the GDP*Pi complex. Evidence for a catalytic intermediate, possibly metaphosphate, is discussed. Galpha GAPs, whether exogenous proteins or effector-linked domains, bind to a discrete locus of Galpha that is composed of Switch I and the N-terminus of Switch II. This site is immediately adjacent to, but does not substantially overlap, the Galpha effector binding site. Interactions of effectors and exogenous GAPs with Galpha proteins can be synergistic or antagonistic, mediated by allosteric interactions among the three molecules. Unlike GAPs for small GTPases, Galpha GAPs supply no catalytic residues, but rather appear to reduce the activation energy for catalytic activation of the Galpha catalytic site

Static Human Detection and Scenario Recognition via Wearable Thermal Sensing System

Conventional wearable sensors are mainly used to detect the physiological and activity information of individuals who wear them, but fail to perceive the information of the surrounding environment. This paper presents a wearable thermal sensing system to detect and perceive the information of surrounding human subjects. The proposed system is developed based on a pyroelectric infrared sensor. Such a sensor system aims to provide surrounding information to blind people and people with weak visual capability to help them adapt to the environment and avoid collision. In order to achieve this goal, a low-cost, low-data-throughput binary sampling and analyzing scheme is proposed. We also developed a conditioning sensing circuit with a low-noise signal amplifier and programmable system on chip (PSoC) to adjust the amplification gain. Three statistical features in information space are extracted to recognize static humans and human scenarios in indoor environments. The results demonstrate that the proposed wearable thermal sensing system and binary statistical analysis method are efficient in static human detection and human scenario perception

Real-time spatial frequency domain imaging by single snapshot multiple frequency demodulation technique

We have presented a novel Single Snapshot Multiple Frequency Demodulation (SSMD) method enabling single snapshot wide field imaging of optical properties of turbid media in the Spatial Frequency Domain. SSMD makes use of the orthogonality of harmonic functions and extracts the modulation transfer function (MTF) at multiple modulation frequencies and of arbitrary orientations and amplitudes simultaneously from a single structured-illuminated image at once. SSMD not only increases significantly the data acquisition speed and reduces motion artifacts but also exhibits excellent noise suppression in imaging as well. The performance of SSMD-SFDI is demonstrated with experiments on both tissue mimicking phantoms and in vivo for recovering optical properties. SSMD is ideal in the implementation of a real-time spatial frequency domain imaging platform, which will open up SFDI for vast applications in, for example, mapping the optical properties of a dynamic turbid medium or monitoring fast temporal evolutions. © (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only

In vivo real-time imaging of cutaneous hemoglobin concentration, oxygen saturation, scattering properties, melanin content, and epidermal thickness with visible spatially modulated light

We present the real-time single snapshot multiple frequency demodulation - spatial frequency domain imaging (SSMD-SFDI) platform implemented with a visible digital mirror device that is capable of imaging and monitoring dynamic turbid medium and processes over a large field of view. One challenge in quantitative imaging of biological tissue such as the skin is the complex structure rendering techniques based on homogeneous medium models to fail. To address this difficulty we have also developed a novel method that maps the layered structure to a homogeneous medium for spatial frequency domain imaging. The varying penetration depth of spatially modulated light on its wavelength and modulation frequency is used to resolve the layered structure. The efficacy of the real-time SSMD-SFDI platform and this two-layer model is demonstrated by imaging forearms of 6 healthy subjects under the reactive hyperemia protocol. The results show that our approach not only successfully decouples light absorption by melanin from that by hemoglobin and yields accurate determination of cutaneous hemoglobin concentration and oxygen saturation, but also provides reliable estimation of the scattering properties, the melanin content and the epidermal thickness in real time. Potential applications of our system in imaging skin physiological and functional states, cancer screening, and microcirculation monitoring are discussed at the end. © 2017 Optical Society of Americ

Single snapshot multiple frequency modulated imaging of subsurface optical properties of turbid media with structured light

We report a novel demodulation method that enables single snapshot wide field imaging of optical properties of turbid media in the Spatial Frequency Domain (SFD). This Single Snapshot Multiple frequency Demodulation (SSMD) method makes use of the orthogonality of harmonic functions to extract the modulation transfer function (MTF) at multiple modulation frequencies simultaneously from a single structured-illuminated image at once. The orientation, frequency, and amplitude of each modulation can be set arbitrarily subject to the limitation of the implementation device. We first validate and compare SSMD to the existing demodulation methods by numerical simulations. The performance of SSMD is then demonstrated with experiments on both tissue mimicking phantoms and in vivo for recovering optical properties by comparing to the standard three-phase demodulation approach. The results show that SSMD increases significantly the data acquisition speed and reduces motion artefacts. SSMD exhibits excellent noise suppression in imaging as well at the rate proportional to the square root of the number of pixels contained in its kernel. SSMD is ideal in the implementation of a real-time spatial frequency domain imaging platform and will open up SFDI for vast applications in imaging and monitoring dynamic turbid medium and processes

Transfer Learning with Optimal Transportation and Frequency Mixup for EEG-based Motor Imagery Recognition

Peer reviewedPublisher PD

Mapping the scientific research on integrated care: a bibliometric and social network analysis

BackgroundIntegrated care (IC) is the cornerstone of the sustainable development of the medical and health system. A thorough examination of the existing scientific literature on IC is essential for assessing the present state of knowledge on this subject. This review seeks to offer an overview of evidence-based knowledge, pinpoint existing knowledge gaps related to IC, and identify areas requiring further research.MethodsData were retrieved from the Web of Science Core Collection, from 2010 to 2020. Bibliometrics and social network analysis were used to explore and map the knowledge structure, research hotspots, development status, academic groups and future development trends of IC.ResultsA total of 7,501 articles were obtained. The number of publications on IC was rising in general. Healthcare science services were the most common topics. The United States contributed the highest number of articles. The level of collaboration between countries and between authors was found to be relatively low. The keywords were stratified into four clusters: IC, depression, integrative medicine, and primary health care. In recent years, complementary medicine has become a hotspot and will continue to be a focus.ConclusionThe study provides a comprehensive analysis of global research hotspots and trends in IC, and highlights the characteristics, challenges, and potential solutions of IC. To address resource fragmentation, collaboration difficulties, insufficient financial incentives, and poor information sharing, international collaboration needs to be strengthened to promote value co-creation and model innovation in IC. The contribution of this study lies in enhancing people’s understanding of the current state of IC research, guiding scholars to discover new research perspectives, and providing valuable references for researchers and policymakers in designing and implementing effective IC strategies