A 1 × 8 Optical Splitter Based on Polycarbonate Multicore Polymer Optical Fibers.

Visible light communication (VLC) is becoming more relevant due to the accelerated advancement of optical fibers. Polymer optical fiber (POF) technology appears to be a solution to the growing demand for improved transmission efficiency and high-speed data rates in the visible light range. However, the VLC system requires efficient splitters with low power losses to expand the optical energy capability and boost system performance. To solve this issue, we propose an effective 1 × 8 optical splitter based on multicore polycarbonate (PC) POF technology suitable for functioning in the green-light spectrum at a 530 nm wavelength. The new design is based on replacing 23 air-hole layers with PC layers over the fiber length, while each PC layer length is suitable for the light coupling of the operating wavelength, which allows us to set the right size of each PC layer between the closer PC cores. To achieve the best result, the key geometrical parameters were optimized through RSoft Photonics CAD suite software that utilized the beam propagation method (BPM) and analysis using MATLAB script codes for finding the tolerance ranges that can support device fabrication. The results show that after a light propagation of 2 mm, an equally green light at a 530 nm wavelength is divided into eight channels with very low power losses of 0.18 dB. Additionally, the splitter demonstrates a large bandwidth of 25 nm and stability with a tolerance range of ±8 nm around the operated wavelength, ensuring robust performance even under laser drift conditions. Furthermore, the splitter can function with 80% and above of the input signal power around the operated wavelength, indicating high efficiency. Therefore, the proposed device has a great potential to boost sensing detection applications, such as Raman spectroscopic and bioengineering applications, using the green light.

BP-M345 as a Basis for the Discovery of New Diarylpentanoids with Promising Antimitotic Activity.

Recently, the diarylpentanoid BP-M345 (5) has been identified as a potent in vitro growth inhibitor of cancer cells, with a GI50 value between 0.17 and 0.45 µM, showing low toxicity in non-tumor cells. BP-M345 (5) promotes mitotic arrest by interfering with mitotic spindle assembly, leading to apoptotic cell death. Following on from our previous work, we designed and synthesized a library of BP-M345 (5) analogs and evaluated the cell growth inhibitory activity of three human cancer cell lines within this library in order to perform structure-activity relationship (SAR) studies and to obtain compounds with improved antimitotic effects. Four compounds (7, 9, 13, and 16) were active, and the growth inhibition effects of compounds 7, 13, and 16 were associated with a pronounced arrest in mitosis. These compounds exhibited a similar or even higher mitotic index than BP-M345 (5), with compound 13 displaying the highest antimitotic activity, associated with the interference with mitotic spindle dynamics, inducing spindle collapse and, consequently, prolonged mitotic arrest, culminating in massive cancer cell death by apoptosis.

A compound Kinoform/Fresnel zone plate lens with 15 nm resolution and high efficiency in soft x-ray.

X-ray microscope as an important nanoprobing tool plays a prevailing role in nano-inspections of materials. Despite the fast advances of high resolution focusing/imaging reported, the efficiency of existing high-resolution zone plates is mostly around 5% in soft x-ray and rapidly goes down to 1%-2% when the resolution approaches 10 nm. It is well known that the rectangular zone shape, beamstop, limited height/width ratios, material absorption of light and structural defects are likely responsible for the limited efficiency. Although zone plates with Kinoform profile are supposed to be efficient, progress for achieving both high resolution (<30 nm) and high efficiency (>5%) have hardly been addressed in soft x-ray. In this work, we propose a compound Kinoform/Fresnel zone plate (CKZP) by combing a dielectric Kinoform zone plate with a 15 nm resolution zone plate. Greyscale electron beam lithography was applied to form the 3D Kinoform zone plate and atomic layer deposition was carried out to form the binary zone plate. Optical characterizations demonstrated 15 nm resolution focusing/imaging with over 7.8% efficiency in soft x-ray. The origin of the efficiency improvement behind the proposed compound lens is theoretically analyzed and discussed.

Precision Heart Rate Estimation Using a PPG Sensor Patch Equipped with New Algorithms of Pre-Quality Checking and Hankel Decomposition.

A new method for accurately estimating heart rates based on a single photoplethysmography (PPG) signal and accelerations is proposed in this study, considering motion artifacts due to subjects' hand motions and walking. The method comprises two sub-algorithms: pre-quality checking and motion artifact removal (MAR) via Hankel decomposition. PPGs and accelerations were collected using a wearable device equipped with a PPG sensor patch and a 3-axis accelerometer. The motion artifacts caused by hand movements and walking were effectively mitigated by the two aforementioned sub-algorithms. The first sub-algorithm utilized a new quality-assessment criterion to identify highly noise-contaminated PPG signals and exclude them from subsequent processing. The second sub-algorithm employed the Hankel matrix and singular value decomposition (SVD) to effectively identify, decompose, and remove motion artifacts. Experimental data collected during hand-moving and walking were considered for evaluation. The performance of the proposed algorithms was assessed using the datasets from the IEEE Signal Processing Cup 2015. The obtained results demonstrated an average error of merely 0.7345 ± 8.1129 beats per minute (bpm) and a mean absolute error of 1.86 bpm for walking, making it the second most accurate method to date that employs a single PPG and a 3-axis accelerometer. The proposed method also achieved the best accuracy of 3.78 bpm in mean absolute errors among all previously reported studies for hand-moving scenarios.

The MATH-BTB BPM3 and BPM5 subunits of Cullin3-RING E3 ubiquitin ligases target PP2CA and other clade A PP2Cs for degradation.

Early abscisic acid signaling involves degradation of clade A protein phosphatases type 2C (PP2Cs) as a complementary mechanism to PYR/PYL/RCAR-mediated inhibition of PP2C activity. At later steps, ABA induces up-regulation of PP2C transcripts and protein levels as a negative feedback mechanism. Therefore, resetting of ABA signaling also requires PP2C degradation to avoid excessive ABA-induced accumulation of PP2Cs. It has been demonstrated that ABA induces the degradation of existing ABI1 and PP2CA through the PUB12/13 and RGLG1/5 E3 ligases, respectively. However, other unidentified E3 ligases are predicted to regulate protein stability of clade A PP2Cs as well. In this work, we identified BTB/POZ AND MATH DOMAIN proteins (BPMs), substrate adaptors of the multimeric cullin3 (CUL3)-RING-based E3 ligases (CRL3s), as PP2CA-interacting proteins. BPM3 and BPM5 interact in the nucleus with PP2CA as well as with ABI1, ABI2, and HAB1. BPM3 and BPM5 accelerate the turnover of PP2Cs in an ABA-dependent manner and their overexpression leads to enhanced ABA sensitivity, whereas bpm3 bpm5 plants show increased accumulation of PP2CA, ABI1 and HAB1, which leads to global diminished ABA sensitivity. Using biochemical and genetic assays, we demonstrated that ubiquitination of PP2CA depends on BPM function. Given the formation of receptor-ABA-phosphatase ternary complexes is markedly affected by the abundance of protein components and ABA concentration, we reveal that BPMs and multimeric CRL3 E3 ligases are important modulators of PP2C coreceptor levels to regulate early ABA signaling as well as the later desensitizing-resetting steps.

Assessing Electroencephalography as a Stress Indicator: A VR High-Altitude Scenario Monitored through EEG and ECG.

Over the last decade, virtual reality (VR) has become an increasingly accessible commodity. Head-mounted display (HMD) immersive technologies allow researchers to simulate experimental scenarios that would be unfeasible or risky in real life. An example is extreme heights exposure simulations, which can be utilized in research on stress system mobilization. Until recently, electroencephalography (EEG)-related research was focused on mental stress prompted by social or mathematical challenges, with only a few studies employing HMD VR techniques to induce stress. In this study, we combine a state-of-the-art EEG wearable device and an electrocardiography (ECG) sensor with a VR headset to provoke stress in a high-altitude scenarios while monitoring EEG and ECG biomarkers in real time. A robust pipeline for signal clearing is implemented to preprocess the noise-infiltrated (due to movement) EEG data. Statistical and correlation analysis is employed to explore the relationship between these biomarkers with stress. The participant pool is divided into two groups based on their heart rate increase, where statistically important EEG biomarker differences emerged between them. Finally, the occipital-region band power changes and occipital asymmetry alterations were found to be associated with height-related stress and brain activation in beta and gamma bands, which correlates with the results of the self-reported Perceived Stress Scale questionnaire.

BPM Support for Patient-Centred Clinical Pathways in Chronic Diseases.

Epidemiological trends over the past decade show a significant worldwide increase in the burden of chronic diseases. At the same time, the human resources of health care are becoming increasingly scarce and expensive. One of the management concepts that can help in solving this problem is business process management (BPM). The results of research conducted in the healthcare sector thus far prove that BPM is an effective tool for optimizing clinical processes, as it allows for the ongoing automatic tracking of key health parameters of an individual patient without the need to involve medical personnel. The aim of this article is to present and evaluate the redesign of diagnostic and therapeutic processes enabling the patient-centric organization of therapy thanks to the use of new telemedicine techniques and elements of hyperautomation. By using an illustrative case study of one of the most common chronic diseases, Chronic Obstructive Pulmonary Disease (COPD), we discuss the use of clinical pathways (CPs) prepared on the basis of the current version of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) as a communication tool between healthcare professionals, the patient and his or her caregivers, as well as the method of identifying and verifying new knowledge generated on an ongoing basis in diagnostic and therapeutic processes. We also show how conducting comprehensive, patient-focused primary health care relieves the health care system, and at the same time, thanks to the use of patient engagement and elements of artificial intelligence (predictive analyses), reduces the significant clinical risk of therapy.

Expression of Lymphatic Markers in the Berger's Space and Bursa Premacularis.

We previously reported that the bursa premacularis (BPM), a peculiar vitreous structure located above the macula, contains numerous cells expressing markers of lymphatic endothelial cells, such as podoplanin and LYVE-1. Herein, we examined the expression of lymphatic markers in the Berger's space (BS), BPM, and vitreous core (VC). BS, BPM, and VC specimens were selectively collected in macular hole and epiretinal membrane patients during vitrectomy and were then immunostained with antibodies for podoplanin, LYVE-1, and fibrillin-1 and -2. By visualization using triamcinolone acetonide, the BS was recognized as a sac-like structure with a septum located behind the lens as well as BPM. Those tissues adhered to the lens or retina in a circular manner by means of a ligament-like structure. Immunostaining showed intense expression of podoplanin and LYVE-1 in the BS. Both BS and BPM stained strongly positive for fibrillin-1 and -2. The VC was faintly stained with antibodies for those lymph-node markers. Our findings indicate that both BS and BPM possibly belong to the lymphatic system, such as lymph nodes, draining excess fluid and waste products into lymphatic vessels in the dura mater of the optic nerve and the ciliary body, respectively, via intravitreal canals.

BP-M345, a New Diarylpentanoid with Promising Antimitotic Activity.

Previously, we reported the in vitro growth inhibitory effect of diarylpentanoid BP-M345 on human cancer cells. Nevertheless, at that time, the cellular mechanism through which BP-M345 exerts its growth inhibitory effect remained to be explored. In the present work, we report its mechanism of action on cancer cells. The compound exhibits a potent tumor growth inhibitory activity with high selectivity index. Mechanistically, it induces perturbation of the spindles through microtubule instability. As a consequence, treated cells exhibit irreversible defects in chromosome congression during mitosis, which induce a prolonged spindle assembly checkpoint-dependent mitotic arrest, followed by massive apoptosis, as revealed by live cell imaging. Collectively, the results indicate that the diarylpentanoid BP-M345 exerts its antiproliferative activity by inhibiting mitosis through microtubule perturbation and causing cancer cell death, thereby highlighting its potential as antitumor agent.

MYB106 is a negative regulator and a substrate for CRL3BPM E3 ligase in regulating flowering time in Arabidopsis thaliana.

Flowering time is crucial for successful reproduction in plants, the onset and progression of which are strictly controlled. However, flowering time is a complex and environmentally responsive history trait and the underlying mechanisms still need to be fully characterized. Post-translational regulation of the activities of transcription factors (TFs) is a dynamic and essential mechanism for plant growth and development. CRL3BPM E3 ligase is a CULLIN3-based E3 ligase involved in orchestrating protein stability via the ubiquitin proteasome pathway. Our study shows that the mutation of MYB106 induced early flowering phenotype while over-expression of MYB106 delayed Arabidopsis flowering. Transcriptome analysis of myb106 mutants reveals 257 differentially expressed genes between wild type and myb106-1 mutants, including Flowering Locus T (FT) which is related to flowering time. Moreover, in vitro electrophoretic mobility shift assays (EMSA), in vivo chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR) assays and dual luciferase assays demonstrate that MYB106 directly binds to the promoter of FT to suppress its expression. Furthermore, we confirm that MYB106 interacts with BPM proteins which are further identified by CRL3BPM E3 ligases as the substrate. Taken together, we have identified MYB106 as a negative regulator in the control of flowering time and a new substrate for CRL3BPM E3 ligases in Arabidopsis.

The Pumilio RNA-binding protein APUM24 regulates seed maturation by fine-tuning the BPM-WRI1 module in Arabidopsis.

Pumilio RNA-binding proteins participate in messenger RNA (mRNA) degradation and translational repression, but their roles in plant development are largely unclear. Here, we show that Arabidopsis PUMILIO PROTEIN24 (APUM24), an atypical Pumilio-homology domain-containing protein, plays an important part in regulating seed maturation, a major stage of plant development. APUM24 is strongly expressed in maturing seeds. Reducing APUM24 expression resulted in abnormal seed maturation, wrinkled seeds, and lower seed oil contents, and APUM24 knockdown resulted in lower levels of WRINKLED 1 (WRI1), a key transcription factor controlling seed oil accumulation, and lower expression of WRI1 target genes. APUM24 reduces the mRNA stability of BTB/POZMATH (BPM) family genes, thus decreasing BPM protein levels. BPM is responsible for the 26S proteasome-mediated degradation of WRI1 and has important functions in plant growth and development. The 3' untranslated regions of BPM family genes contain putative Pumilio response elements (PREs), which are bound by APUM24. Reduced BPM or increased WRI1 expression rescued the deficient seed maturation of apum24-2 knockdown mutants, and APUM24 overexpression resulted in increased seed size and weight. Therefore, APUM24 is crucial to seed maturation through its action as a positive regulator fine-tuning the BPM-WRI1 module, making APUM24 a promising target for breeding strategies to increase crop yields.

X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists.

We present a robust protocol based on iterations of free energy perturbation (FEP) calculations, chemical synthesis, biophysical mapping and X-ray crystallography to reveal the binding mode of an antagonist series to the A2A adenosine receptor (AR). Eight A2A AR binding site mutations from biophysical mapping experiments were initially analyzed with sidechain FEP simulations, performed on alternate binding modes. The results distinctively supported one binding mode, which was subsequently used to design new chromone derivatives. Their affinities for the A2A AR were experimentally determined and investigated through a cycle of ligand-FEP calculations, validating the binding orientation of the different chemical substituents proposed. Subsequent X-ray crystallography of the A2A AR with a low and a high affinity chromone derivative confirmed the predicted binding orientation. The new molecules and structures here reported were driven by free energy calculations, and provide new insights on antagonist binding to the A2A AR, an emerging target in immuno-oncology.

Insufficient slow-flow suppression mimicking aneurysm wall enhancement in magnetic resonance vessel wall imaging: a phantom study.

OBJECTIVE: MR vessel wall imaging (VWI) is increasingly performed in clinical settings to support treatment decision-making regarding intracranial aneurysms. Aneurysm wall enhancement after contrast agent injection is expected to be related to aneurysm instability and rupture status. However, the authors hypothesize that slow-flow artifacts mimic aneurysm wall enhancement. Therefore, in this phantom study they assess the effect of slow flow on wall-like enhancement by using different MR VWI techniques. METHODS: The authors developed an MR-compatible aneurysm phantom model, which was connected to a pump to enable pulsatile inflow conditions. For VWI, 3D turbo spin echo sequences-both with and without motion-sensitized driven equilibrium (MSDE) and delay alternating with nutation for tailored excitation (DANTE) preparation pulses-were performed using a 3-T MR scanner. VWI was acquired both before and after Gd contrast agent administration by using two different pulsatile inflow conditions (2.5 ml/sec peak flow at 77 and 48 beats per minute). The intraluminal signal intensity along the aneurysm wall was analyzed to assess the performance of slow-flow suppression. RESULTS: The authors observed wall-like enhancement after contrast agent injection, especially in low pump rate settings. Preparation pulses, in particular the DANTE technique, improved the performance of slow-flow suppression. CONCLUSIONS: Near-wall slow flow mimics wall enhancement in VWI protocols. Therefore, VWI should be carefully interpreted. Preparation pulses improve slow-flow suppression, and therefore the authors encourage further development and clinical implementation of these techniques.

Timing of post-resistance exercise nutrient ingestion: effects on gastric emptying and glucose and amino acid responses in humans.

This study examined the effects of post-resistance exercise protein ingestion timing on the rate of gastric emptying (GE) and blood glucose (BG) and plasma branched-chain amino acid (BCAA) responses. In all, eleven healthy participants randomly ingested 400 ml of a nutrient-rich drink containing 12 g carbohydrates and 20 g protein at rest (Con), at 5 min (post-exercise (PE)-5) or at 30 min (PE-30) after a single bout of strenuous resistance exercises. The first and second sets comprised ten repetitions at 50 % of each participant's one-repetition maximum (1RM). The third, fourth and fifth sets comprised ten repetitions at 75 % of 1RM, and the sixth set involved repeated repetitions until exhaustion. Following ingestion of the nutrient-rich drink, we assessed the GE rate using 13C-sodium acetate breath test and evaluated two parameters according to the T max-calc (time when the recovery per hour is maximised), which is a standard analytical method, and T 1/2 (time when the total cumulative dose of [13CO2] reaches one-half). T max-calc and T 1/2 were slower for the PE-5 condition than for either the PE-30 or Con condition (T max-calc; Con: 53 (sd 7) min, PE-5: 83 (sd 16) min, PE-30: 62 (sd 9) min, T 1/2; Con: 91 (sd 7) min, PE-5: 113 (sd 21) min, PE-30: 91 (sd 11) min, P<0·05). BG and BCAA responses were also slower for the PE-5 condition than for either the PE-30 or Con condition. Ingesting nutrients immediately after strenuous resistance exercise acutely delayed GE, which affected BG and plasma BCAA levels in blood circulation.

An Energy-Efficient Algorithm for Wearable Electrocardiogram Signal Processing in Ubiquitous Healthcare Applications.

Rapid progress and emerging trends in miniaturized medical devices have enabled the un-obtrusive monitoring of physiological signals and daily activities of everyone's life in a prominent and pervasive manner. Due to the power-constrained nature of conventional wearable sensor devices during ubiquitous sensing (US), energy-efficiency has become one of the highly demanding and debatable issues in healthcare. This paper develops a single chip-based wearable wireless electrocardiogram (ECG) monitoring system by adopting analog front end (AFE) chip model ADS1292R from Texas Instruments. The developed chip collects real-time ECG data with two adopted channels for continuous monitoring of human heart activity. Then, these two channels and the AFE are built into a right leg drive right leg drive (RLD) driver circuit with lead-off detection and medical graded test signal. Human ECG data was collected at 60 beats per minute (BPM) to 120 BPM with 60 Hz noise and considered throughout the experimental set-up. Moreover, notch filter (cutoff frequency 60 Hz), high-pass filter (cutoff frequency 0.67 Hz), and low-pass filter (cutoff frequency 100 Hz) with cut-off frequencies of 60 Hz, 0.67 Hz, and 100 Hz, respectively, were designed with bilinear transformation for rectifying the power-line noise and artifacts while extracting real-time ECG signals. Finally, a transmission power control-based energy-efficient (ETPC) algorithm is proposed, implemented on the hardware and then compared with the several conventional TPC methods. Experimental results reveal that our developed chip collects real-time ECG data efficiently, and the proposed ETPC algorithm achieves higher energy savings of 35.5% with a slightly larger packet loss ratio (PLR) as compared to conventional TPC (e.g., constant TPC, Gao's, and Xiao's methods).

Template-Assisted Direct Growth of 1 Td/in(2) Bit Patterned Media.

We present a method for growing bit patterned magnetic recording media using directed growth of sputtered granular perpendicular magnetic recording media. The grain nucleation is templated using an epitaxial seed layer, which contains Pt pillars separated by amorphous metal oxide. The scheme enables the creation of both templated data and servo regions suitable for high density hard disk drive operation. We illustrate the importance of using a process that is both topographically and chemically driven to achieve high quality media.

Surface plasmon resonance spectroscopy for characterisation of membrane protein-ligand interactions and its potential for drug discovery.

Surface plasmon resonance (SPR) spectroscopy is a rapidly developing technique for the study of ligand binding interactions with membrane proteins, which are the major molecular targets for validated drugs and for current and foreseeable drug discovery. SPR is label-free and capable of measuring real-time quantitative binding affinities and kinetics for membrane proteins interacting with ligand molecules using relatively small quantities of materials and has potential to be medium-throughput. The conventional SPR technique requires one binding component to be immobilised on a sensor chip whilst the other binding component in solution is flowed over the sensor surface; a binding interaction is detected using an optical method that measures small changes in refractive index at the sensor surface. This review first describes the basic SPR experiment and the challenges that have to be considered for performing SPR experiments that measure membrane protein-ligand binding interactions, most importantly having the membrane protein in a lipid or detergent environment that retains its native structure and activity. It then describes a wide-range of membrane protein systems for which ligand binding interactions have been characterised using SPR, including the major drug targets G protein-coupled receptors, and how challenges have been overcome for achieving this. Finally it describes some recent advances in SPR-based technology and future potential of the technique to screen ligand binding in the discovery of drugs. This article is part of a Special Issue entitled: Structural and biophysical characterisation of membrane protein-ligand binding.

Upgrade of beamline BL08B at Taiwan Light Source from a photon-BPM to a double-grating SGM beamline.

During the last 20 years, beamline BL08B has been upgraded step by step from a photon beam-position monitor (BPM) to a testing beamline and a single-grating beamline that enables experiments to record X-ray photo-emission spectra (XPS) and X-ray absorption spectra (XAS) for research in solar physics, organic semiconductor materials and spinel oxides, with soft X-ray photon energies in the range 300-1000 eV. Demands for photon energy to extend to the extreme ultraviolet region for applications in nano-fabrication and topological thin films are increasing. The basic spherical-grating monochromator beamline was again upgraded by adding a second grating that delivers photons of energy from 80 to 420 eV. Four end-stations were designed for experiments with XPS, XAS, interstellar photoprocess systems (IPS) and extreme-ultraviolet lithography (EUVL) in the scheduled beam time. The data from these experiments show a large count rate in core levels probed and excellent statistics on background normalization in the L-edge adsorption spectrum.

The Business Process Management for Healthcare (BPM+ Health) Consortium: motivation, methodology, and deliverables for enabling clinical knowledge interoperability (CKI).

OBJECTIVES: To enhance the Business Process Management (BPM)+ Healthcare language portfolio by incorporating knowledge types not previously covered and to improve the overall effectiveness and expressiveness of the suite to improve Clinical Knowledge Interoperability. METHODS: We used the BPM+ Health and Object Management Group (OMG) standards development methodology to develop new languages, following a gap analysis between existing BPM+ Health languages and clinical practice guideline knowledge types. Proposal requests were developed based on these requirements, and submission teams were formed to respond to them. The resulting proposals were submitted to OMG for ratification. RESULTS: The BPM+ Health family of languages, which initially consisted of the Business Process Model and Notation, Decision Model and Notation, and Case Model and Notation, was expanded by adding 5 new language standards through the OMG. These include Pedigree and Provenance Model and Notation for expressing epistemic knowledge, Knowledge Package Model and Notation for supporting packaging knowledge, Shared Data Model and Notation for expressing ontic knowledge, Party Model and Notation for representing entities and organizations, and Specification Common Elements, a language providing a standard abstract and reusable library that underpins the 4 new languages. DISCUSSION AND CONCLUSION: In this effort, we adopted a strategy of separation of concerns to promote a portfolio of domain-agnostic, independent, but integrated domain-specific languages for authoring medical knowledge. This strategy is a practical and effective approach to expressing complex medical knowledge. These new domain-specific languages offer various knowledge-type options for clinical knowledge authors to choose from without potentially adding unnecessary overhead or complexity.

A transgenic zebrafish model of a human cardiac sodium channel mutation exhibits bradycardia, conduction-system abnormalities and early death.

The recent exponential increase in human genetic studies due to the advances of next generation sequencing has generated unprecedented numbers of new gene variants. Determining which of these are causative of human disease is a major challenge. In-vitro studies and murine models have been used to study inherited cardiac arrhythmias but have several limitations. Zebrafish models provide an attractive alternative for modeling human heart disease due to similarities in cardiac electrophysiology and contraction, together with ease of genetic manipulation, external development and optical transparency. Although zebrafish cardiac mutants and morphants have been widely used to study loss and knockdown of zebrafish gene function, the phenotypic effects of human dominant-negative gene mutations expressed in transgenic zebrafish have not been evaluated. The aim of this study was to generate and characterize a transgenic zebrafish arrhythmia model harboring the pathogenic human cardiac sodium channel mutation SCN5A-D1275N, that has been robustly associated with a range of cardiac phenotypes, including conduction disease, sinus node dysfunction, atrial and ventricular arrhythmias, and dilated cardiomyopathy in humans and in mice. Stable transgenic fish with cardiac expression of human SCN5A were generated using Tol2-mediated transgenesis and cardiac phenotypes were analyzed using video microscopy and ECG. Here we show that transgenic zebrafish expressing the SCN5A-D1275N mutation, but not wild-type SCN5A, exhibit bradycardia, conduction-system abnormalities and premature death. We furthermore show that SCN5A-WT, and to a lesser degree SCN5A-D1275N, are able to compensate the loss of endogenous zebrafish cardiac sodium channels, indicating that the basic pathways, through which SCN5A acts, are conserved in teleosts. This proof-of-principle study suggests that zebrafish may be highly useful in vivo models to differentiate functional from benign human genetic variants in cardiac ion channel genes in a time- and cost-efficient manner. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes".