Femtosecond-laser-written superficial cladding waveguides in Nd:CaF 2 crystal

We report on the superficial cladding waveguides fabricated by direct femtosecond laser writing in Nd: CaF2 crystal with three different groups of parameters. The lowest propagation loss of waveguides has been determined to be 0.7 dB/cm at wavelength of 632.8 nm along TE polarization. The near fundamental modal distributions have been imaged through the end-face coupling technique. The guidance of the waveguides is found to possess low sensitivity on polarization of the probe light. By using a confocal microscope system, the micro-photoluminescence mappings and micro-fluorescence spectra are also obtained, which indicates the photoluminescence features of the Nd3+ ions are well preserved in the waveguide cores after direct femtosecond laser writing.The work is supported by Specialized Research Fund for the Doctoral Program of Higher Education of China (20130131130001); the 111 Project (No. B13029); Fundamental Research Funds for Shandong University (No. 2014JC002). JRVA thanks support from Junta de Castilla y León (Project SA116U13)

Modeling CICR in rat ventricular myocytes: voltage clamp studies

<p>Abstract</p> <p>Background</p> <p>The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect <it>Ca</it>²⁺loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR <it>Ca</it>²⁺release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic <it>Ca</it>²⁺concentration ([<it>Ca</it>²⁺]<it>_myo</it>).</p> <p>Methods</p> <p>The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed <it>Ca</it>²⁺channels (trigger-channel and release-channel). It releases <it>Ca</it>²⁺flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[<it>Ca</it>²⁺]<it>_myo</it>.</p> <p>Results</p> <p>Our model reproduces measured VC data published by several laboratories, and generates graded <it>Ca</it>²⁺release at high <it>Ca</it>²⁺gain in a homeostatically-controlled environment where [<it>Ca</it>²⁺]<it>_myo</it>is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR <it>Ca</it>²⁺release, its activation by trigger <it>Ca</it>²⁺, and its refractory characteristics mediated by the luminal SR <it>Ca</it>²⁺sensor. Proper functioning of the DCU, sodium-calcium exchangers and SERCA pump are important in achieving negative feedback control and hence <it>Ca</it>²⁺homeostasis.</p> <p>Conclusions</p> <p>We examine the role of the above <it>Ca</it>²⁺regulating mechanisms in handling various types of induced disturbances in <it>Ca</it>²⁺levels by quantifying cellular <it>Ca</it>²⁺balance. Our model provides biophysically-based explanations of phenomena associated with CICR generating useful and testable hypotheses.</p

Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes.

In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. Modulating their expression and/or function can impact the shape of the AP and consequently modify nociceptive transmission, a process that is observed in persistent pain conditions. Post-translational modification (PTM) of Navs is a well-known process that modifies their expression and function. In chronic pain syndromes, the release of inflammatory molecules into the direct environment of dorsal root ganglia (DRG) sensory neurons leads to an abnormal activation of enzymes that induce Navs PTM. The addition of small molecules, i.e., peptides, phosphoryl groups, ubiquitin moieties and/or carbohydrates, can modify the function of Navs in two different ways: via direct physical interference with Nav gating, or via the control of Nav trafficking. Both mechanisms have a profound impact on neuronal excitability. In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain

Köebner phenomenon induced by cupping therapy in a psoriasis patient

Psoriasis is a chronic, immune-mediated inflammatory and refractory disease. The koebner phenomenon, which can be induced by trauma, is common in psoriasis patients. Herein, we report a patient with psoriasis who was treated by cupping therapy and subsequently developed the koebner phenomenon (KP) at the cupped sites. To our knowledge, it is the first report about cupping therapy leading to KP in a psoriasis patient

Atomic Defect Induced Saturable Absorption of Hexagonal Boron Nitride in Near Infrared Band for Ultrafast Lasing Applications

Defect-induced phenomena in 2D materials has received increasing interest among researchers due to the novel properties correlated with precise modification of materials. We performed a study of the nonlinear saturable absorption of the boron-atom-vacancy defective hexagonal boron nitride (h-BN) thin film at a wavelength of ~1 μm and its applications in ultrafast laser generation. The h-BN is with wide band gap of ~6 eV. Our investigation shows that the defective h-BN has a wide absorption band from visible to near infrared regimes. First-principle calculations based on density functional theory (DFT) indicate that optical property changes may be attributed to the boron-vacancy-related defects. The photoluminescence spectrum shows a strong emission peak at ~1.79 eV. The ultrafast Z-scan measurement shows saturable absorbance response has been detected for the defective h-BN with saturation intensity of ~1.03 GW/cm2 and modulation depth of 1.1%. In addition, the defective h-BN has been applied as a new saturable absorber (SA) to generate laser pulses through the passively Q-switched mode-locking configuration. Based on a Nd:YAG waveguide platform, 8.7 GHz repetition rate and 55 ps pulse duration of the waveguide laser have been achieved. Our results suggest potential applications of defective h-BN for ultrafast lasing and integrated photonics

Effect of Thrombolysis on Circulating Microparticles in Patients with ST-Segment Elevation Myocardial Infarction

Objective. We demonstrated that circulating microparticles (MPs) are increased in patients with coronary heart disease (both chronic coronary syndrome (CCS) and acute coronary syndrome). Whether thrombolysis affects MPs in patients with ST-segment elevation myocardial infarction (STEMI) with or without percutaneous coronary intervention (PCI) is unknown. Methods. This study was divided into three groups: STEMI patients with thrombolysis (n=18) were group T, patients with chronic coronary syndrome (n=20) were group CCS, and healthy volunteers (n=20) were the control group. Fasting venous blood was extracted from patients in the CCS and control groups, and venous blood was extracted from patients in the T group before (pre-T) and 2 hours after (post-T) thrombolysis. MPs from each group were obtained by centrifugation. After determining the concentration, the effects of MPs on endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in rat myocardial tissue in vitro were detected by immunohistochemistry and western blotting. Changes in nitric oxide (NO) and oxygen free radicals (O2•–) were also detected. The effect of MPs on vasodilation in isolated rat thoracic aortae was detected. Results. Compared with that in the control group (2.60±0.38 mg/ml), the concentration of MPs was increased in patients with CCS (3.49±0.72 mg/ml) and in STEMI patients before thrombolysis (4.17±0.58 mg/ml). However, thrombolysis did not further increase MP levels (post-T, 4.23±1.01 mg/ml) compared with those in STEMI patients before thrombolysis. Compared with those in the control group, MPs in both CCS and STEMI patients before thrombolysis inhibited the expression of eNOS (both immunohistochemistry and western blot analysis of phosphorylation at Ser1177), NO production in the isolated myocardium and vasodilation in vitro and stimulated the expression of iNOS (immunohistochemistry and western blot analysis of phosphorylation at Thr495), and the generation of O2•– in the isolated myocardium. The effects of MPs were further enhanced by MPs from STEMI patients 2 hours after thrombolysis. Conclusion. Changes in MP function after thrombolysis may be one of the mechanisms leading to ischemia–reperfusion after thrombolysis