Myosin light chain kinase is not a regulator of synaptic vesicle trafficking during repetitive exocytosis in cultured hippocampal neurons

The mechanism by which synaptic vesicles (SVs) are recruited to the release site is poorly understood. One candidate mechanism for trafficking of SVs is the myosin-actin motor system. Myosin activity is modulated by myosin light chain kinase (MLCK), which in turn is activated by calmodulin. Ca2+ signaling in presynaptic terminals, therefore, may serve to regulate SV mobility along actin filaments via MLCK. Previous studies in different types of synapses have supported such a hypothesis. Here, we further investigated the role of MLCK in neurotransmitter release at glutamatergic synapses in cultured hippocampal neurons by examining the effects of two MLCK inhibitors, 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine(.)HCl (ML-7) and wortmannin. Bath application of ML-7 enhanced short-term depression of EPSCs to repetitive stimulation, whereas it reduced presynaptic release probability. However, ML-7 also inhibited action potential amplitude and voltage-gated Ca2+ channel currents. These effects were not mimicked by wortmannin, suggesting that ML-7 was not specific to MLCK in hippocampal neurons. When SV exocytosis was directly triggered by a Ca2+ ionophore, calcimycin, to bypass voltage-gated Ca2+ channels, ML-7 had no effect on neurotransmitter release. Furthermore, when SV exocytosis elicited by electrical field stimulation was monitored by styryl dye, FM1-43 [N-(3-triethylammoniumpropyl)-4-(4-( dibutylamino) styryl) pyridinium dibromide], the unloading kinetics of the dye was not altered in the presence of wortmannin. These data indicate that MLCK is not a major regulator of presynaptic SV trafficking during repetitive exocytosis at hippocampal synapses

Frequency-Dependent Squeeze Amplitude Attenuation and Squeeze Angle Rotation by Electromagnetically Induced Transparency for Gravitational Wave Interferometers

We study the effects of frequency-dependent squeeze amplitude attenuation and squeeze angle rotation by electromagnetically induced transparency (EIT) on gravitational wave (GW) interferometers. We propose the use of low-pass, band-pass, and high-pass EIT filters, an S-shaped EIT filter, and an intra-cavity EIT filter to generate frequency-dependent squeezing for injection into the antisymmetric port of GW interferometers. We find that the EIT filters have several advantages over the previous filter designs with regard to optical losses, compactness, and the tunability of the filter linewidth.Comment: 4 page

Non-invasive Measurements of Cavity Parameters by Use of Squeezed Vacuum

We propose and experimentally demonstrate a method for non-invasive measurements of cavity parameters by injection of squeezed vacuum into an optical cavity. The principle behind this technique is the destruction of the correlation between upper and lower quantum sidebands with respect to the carrier frequency when the squeezed field is incident on the cavity. This method is especially useful for ultrahigh $Q$ cavities, such as whispering gallery mode (WGM) cavities, in which absorption and scattering by light-induced nonlinear processes inhibit precise measurements of the cavity parameters. We show that the linewidth of a test cavity is measured to be $\gamma = 844\pm40$ kHz, which agrees with the classically measured linewidth of the cavity within the uncertainty ($\gamma=856\pm34$ kHz).Comment: 6 pages, 4 figure

pyPPG: A Python toolbox for comprehensive photoplethysmography signal analysis

Photoplethysmography is a non-invasive optical technique that measures changes in blood volume within tissues. It is commonly and increasingly used for in a variety of research and clinical application to assess vascular dynamics and physiological parameters. Yet, contrary to heart rate variability measures, a field which has seen the development of stable standards and advanced toolboxes and software, no such standards and open tools exist for continuous photoplethysmogram (PPG) analysis. Consequently, the primary objective of this research was to identify, standardize, implement and validate key digital PPG biomarkers. This work describes the creation of a standard Python toolbox, denoted pyPPG, for long-term continuous PPG time series analysis recorded using a standard finger-based transmission pulse oximeter. The improved PPG peak detector had an F1-score of 88.19% for the state-of-the-art benchmark when evaluated on 2,054 adult polysomnography recordings totaling over 91 million reference beats. This algorithm outperformed the open-source original Matlab implementation by ~5% when benchmarked on a subset of 100 randomly selected MESA recordings. More than 3,000 fiducial points were manually annotated by two annotators in order to validate the fiducial points detector. The detector consistently demonstrated high performance, with a mean absolute error of less than 10 ms for all fiducial points. Based on these fiducial points, pyPPG engineers a set of 74 PPG biomarkers. Studying the PPG time series variability using pyPPG can enhance our understanding of the manifestations and etiology of diseases. This toolbox can also be used for biomarker engineering in training data-driven models. pyPPG is available on physiozoo.orgComment: The manuscript was submitted to "Physiological Measurement" on September 5, 202

Robust peak detection for photoplethysmography signal analysis

Efficient and accurate evaluation of long-term photoplethysmography (PPG) recordings is essential for both clinical assessments and consumer products. In 2021, the top opensource peak detectors were benchmarked on the Multi-Ethnic Study of Atherosclerosis (MESA) database consisting of polysomnography (PSG) recordings and continuous sleep PPG data, where the Automatic Beat Detector (Aboy) had the best accuracy. This work presents Aboy++, an improved version of the original Aboy beat detector. The algorithm was evaluated on 100 adult PPG recordings from the MESA database, which contains more than 4.25 million reference beats. Aboy++ achieved an F1-score of 85.5%, compared to 80.99% for the original Aboy peak detector. On average, Aboy++ processed a 1 hour-long recording in less than 2 seconds. This is compared to 115 seconds (i.e., over 57-times longer) for the open-source implementation of the original Aboy peak detector. This study demonstrated the importance of developing robust algorithms like Aboy++ to improve PPG data analysis and clinical outcomes. Overall, Aboy++ is a reliable tool for evaluating long-term wearable PPG measurements in clinical and consumer contexts.Comment: 4 pages, 1 figure, 50th Computing in Cardiology conference in Atlanta, Georgia, USA on 1st - 4th October 202

Role of phason-defects on the conductance of a 1-d quasicrystal

We have studied the influence of a particular kind of phason-defect on the Landauer resistance of a Fibonacci chain. Depending on parameters, we sometimes find the resistance to decrease upon introduction of defect or temperature, a behavior that also appears in real quasicrystalline materials. We demonstrate essential differences between a standard tight-binding model and a full continuous model. In the continuous case, we study the conductance in relation to the underlying chaotic map and its invariant. Close to conducting points, where the invariant vanishes, and in the majority of cases studied, the resistance is found to decrease upon introduction of a defect. Subtle interference effects between a sudden phason-change in the structure and the phase of the wavefunction are also found, and these give rise to resistive behaviors that produce exceedingly simple and regular patterns.Comment: 12 pages, special macros jnl.tex,reforder.tex, eqnorder.tex. arXiv admin note: original tex thoroughly broken, figures missing. Modified so that tex compiles, original renamed .tex.orig in source

Photothermal Fluctuations as a Fundamental Limit to Low-Frequency Squeezing in a Degenerate Optical Parametric Amplifier

We study the effect of photothermal fluctuations on squeezed states of light through the photo-refractive effect and thermal expansion in a degenerate optical parametric amplifier (OPA). We also discuss the effect of the photothermal noise in various cases and how to minimize its undesirable consequences. We find that the photothermal noise in the OPA introduces a significant amount of noise on phase squeezed beams, making them less than ideal for low frequency applications such as gravitational wave (GW) interferometers, whereas amplitude squeezed beams are relatively immune to the photothermal noise and may represent the best choice for application in GW interferometers

Knot Floer homology detects fibred knots

Ozsv\'ath and Szab\'o conjectured that knot Floer homology detects fibred knots in $S^3$. We will prove this conjecture for null-homologous knots in arbitrary closed 3--manifolds. Namely, if $K$ is a knot in a closed 3--manifold $Y$, $Y-K$ is irreducible, and $\hat{HFK}(Y,K)$ is monic, then $K$ is fibred. The proof relies on previous works due to Gabai, Ozsv\'ath--Szab\'o, Ghiggini and the author. A corollary is that if a knot in $S^3$ admits a lens space surgery, then the knot is fibred.Comment: version 4: incorporates referee's suggestions, to appear in Inventiones Mathematica

Quiescience as a mechanism for cyclical hypoxia and acidosis

Tumour tissue characteristically experiences fluctuations in substrate supply. This unstable microenvironment drives constitutive metabolic changes within cellular populations and, ultimately, leads to a more aggressive phenotype. Previously, variations in substrate levels were assumed to occur through oscillations in the hæmodynamics of nearby and distant blood vessels. In this paper we examine an alternative hypothesis, that cycles of metabolite concentrations are also driven by cycles of cellular quiescence and proliferation. Using a mathematical modelling approach, we show that the interdependence between cell cycle and the microenvironment will induce typical cycles with the period of order hours in tumour acidity and oxygenation. As a corollary, this means that the standard assumption of metabolites entering diffusive equilibrium around the tumour is not valid; instead temporal dynamics must be considered