Experimental and Monte Carlo studies of Ca2+ channel function and fast transmitter release at presynaptic active zones of the frog neuromuscular junction

During fast chemical synaptic transmission, neurotransmitter release is triggered by calcium (Ca2+) influx through voltage-gated Ca2+ channels (VGCCs) opened by an action potential (AP) at the nerve terminal. The magnitude and time course of neurotransmitter release is critically determined by the coupling between Ca2+ channels and synaptic vesicles. Studies of the quantitative dependence of transmitter release on the number of VGCCs provide important information for our understanding of the mechanisms that underlie the control and modulation of presynaptic release probability and kinetics. Using high-resolution calcium imaging techniques and variance analysis, I have determined the number of functional VGCCs within individual active zones (AZs) of the adult frog neuromuscular junction (NMJ) and their opening probability in response to single AP stimulation. The results have shown that the average number of VGCCs within individual active zones was relatively small (~28) and the average opening probability of individual Ca2+ channels during a presynaptic AP was very low (~0.24). Therefore, it is predicted that an action potential induced opening of relatively few Ca2+ channels in a single active zone. Furthermore, by combining pharmacological channel block, calcium imaging, postsynaptic recording, and 3D Monte Carlo diffusion-reaction simulations, I have studied the coupling of single Ca2+ channel openings to the triggering of vesicle fusion. I have provided evidence that Ca2+ entry through single open Ca2+ channels at the nerve terminal can be imaged directly and that such Ca2+ flux is sufficient to trigger synaptic vesicle fusion. I have further shown that following a single AP, the Ca2+ influx through a single open channel plays the predominant role in evoking neurotransmitter release, while Ca2+ ions derived from a collection of open Ca2+ channels are rarely required for vesicle exocytosis at this synapse

CT-guided 125I brachytherapy combined with chemotherapy for the treatment of unresectable or locally advanced pancreatic carcinoma

PURPOSEWe aimed to explore the feasibility and clinical effectiveness of percutaneous CT-guided iodine-125 (¹²⁵I) brachytherapy combined with chemotherapy for the treatment of patients with unresectable or locally advanced pancreatic carcinoma (PC).METHODSWe retrospectively reviewed 66 patients with Stage III and IV PC who had received chemotherapy. A total of 35 (53%) patients receiving 125I brachytherapy and chemotherapy (gemcitabine + cisplatin, GP) were classified as Group A, and 31 (47%) patients who received GP chemotherapy alone were categorized as Group B. The evaluated indications were local control rate (LCR), local progression-free survival (LPFS), overall survival (OS), treatment-related complications, and the degree of symptom relief. Kaplan-Meier curves, log-rank test and Cox regression models were generated and used for further analysis to identify predictors of outcomes.RESULTSThe median follow-up time was 6.00±0.84 months. The 1-, 3-, 6-, 12- and 18-month LCRs for Group A were 100% (35/35), 89.3% (25/28), 71.4% (15/21), 37.5% (3/8) and 33.3% (1/3), respectively; and those for Group B were 87.1% (27/31), 69.6% (16/23), 41.2% (7/17), 14.3% (1/7) and 0% (0/3), respectively. The LCR differed at 1-, 3- and 6-months (P = 0.032; P = 0.009; P = 0.030; respectively). The median LPFS was 7.00±0.30 months and 5.00±0.75 months for Groups A and B (P = 0.023), respectively; however, the median OS of the groups were not significantly different (8.00±0.77 months vs. 6.00±1.04 months. P = 0.917). No life-threatening complications occurred during or after the procedures. Patients in Group A experienced better pain control and relief of abdominal distension than those in Group B.CONCLUSIONCT-guided 125I brachytherapy is a feasible, safe, and valuable treatment for patients with unresectable PC

Exploring the Potential of Integrated Optical Sensing and Communication (IOSAC) Systems with Si Waveguides for Future Networks

Advanced silicon photonic technologies enable integrated optical sensing and communication (IOSAC) in real time for the emerging application requirements of simultaneous sensing and communication for next-generation networks. Here, we propose and demonstrate the IOSAC system on the silicon nitride (SiN) photonics platform. The IOSAC devices based on microring resonators are capable of monitoring the variation of analytes, transmitting the information to the terminal along with the modulated optical signal in real-time, and replacing bulk optics in high-precision and high-speed applications. By directly integrating SiN ring resonators with optical communication networks, simultaneous sensing and optical communication are demonstrated by an optical signal transmission experimental system using especially filtering amplified spontaneous emission spectra. The refractive index (RI) sensing ring with a sensitivity of 172 nm/RIU, a figure of merit (FOM) of 1220, and a detection limit (DL) of 8.2*10-6 RIU is demonstrated. Simultaneously, the 1.25 Gbps optical on-off-keying (OOK) signal is transmitted at the concentration of different NaCl solutions, which indicates the bit-error-ratio (BER) decreases with the increase in concentration. The novel IOSAC technology shows the potential to realize high-performance simultaneous biosensing and communication in real time and further accelerate the development of IoT and 6G networks.Comment: 11pages, 5 figutre

Retrogressive thaw slumps along the Qinghai-Tibet Engineering Corridor: a comprehensive inventory and their distribution characteristics

The important Qinghai&ndash;Tibet Engineering Corridor (QTEC) covers the part of the Highway and Railway underlain by permafrost. The permafrost on the QTEC is sensitive to climate warming and human disturbance and suffers accelerating degradation. Retrogressive thaw slumps (RTSs) are slope failures due to the thawing of ice-rich permafrost. They typically retreat and expand at high rates, damaging infrastructure, and releasing carbon preserved in frozen ground. Along the critical and essential corridor, RTSs are commonly distributed but remain poorly investigated. To compile the first comprehensive inventory of RTSs, this study uses an iteratively semi-automatic method built on deep learning to delineate thaw slumps in the 2019 PlanetScope CubeSat images over a &sim;&thinsp;54&thinsp;000&thinsp;km2 corridor area. The method effectively assesses every image pixel using DeepLabv3+ with limited training samples and manually inspects the deep-learning-identified thaw slumps based on their geomorphic features and temporal changes. The inventory includes 875 RTSs, of which 474 are clustered in the Beiluhe region, and 38 are near roads or railway lines. The dataset is available at https://doi.org/10.5281/zenodo.6397029​​​​​​​ (Xia et al., 2021a), with the Chinese version at DOI: https://doi.org/10.11888/Cryos.tpdc.272672 (Xia et al.&nbsp;2021b). These RTSs tend to be located on north-facing slopes with gradients of 1.2&ndash;18.1∘ and distributed at medium elevations ranging from 4511 to 5212&thinsp;m&thinsp;a.s.l. They prefer to develop on land receiving relatively low annual solar radiation (from 2900 to 3200 &thinsp;kWh&thinsp;m&minus;2), alpine meadow covered, and loam underlay. Our results provide a significant and fundamental benchmark dataset for quantifying thaw slump changes in this vulnerable region undergoing strong climatic warming and extensive human activities. &nbsp;</p