Evaluation of coronary arteries in non-ischemic cardiomyopathies: A case report

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a congenital cardiac disease with myocardial involvement, most probably right ventricular (RV) dysfunction, accounting for 20 of sudden cardiac deaths. Characterized by the fibro-fatty infiltration of the RV free wall, ARVD/C presents in adolescents with ventricular arrhythmias and heart failure symptoms and as biventricular failure in adults. The coronary risk in these patients is not clear. We present an incidental finding: the left anterior descending artery cut-off in a middle-aged man with ARVD/C. He had been under treatment for heart failure symptoms, which had decompensated frequently commencing 6 months earlier, and therefore he was scheduled for stem cell injection. He had no chest pain or coronary artery disease risk factors. Two-dimensional transthoracic echocardiography demonstrated RV enlargement with moderate to severe dysfunction and left ventricular ejection fraction (LVEF) of 35-40, which was 45-50 two years before. Selective coronary angiography performed 8 years previously was normal but a new one revealed the cut-off of the left anterior descending artery at the proximal portion, for which percutaneous coronary intervention was performed and showed no significant lesion in the other vessels. One should consider coronary artery disease in uncontrolled heart failure with LVEF reduction, even in the absence of typical chest pain. It may not be the natural course of the underlying disease. © 2016, Tehran Heart Center. All rights reserved

Evidence that PUBO outperforms QUBO when solving continuous optimization problems with the QAOA

Quantum computing provides powerful algorithmic tools that have been shown to outperform established classical solvers in specific optimization tasks. A core step in solving optimization problems with known quantum algorithms such as the Quantum Approximate Optimization Algorithm (QAOA) is the problem formulation. While quantum optimization has historically centered around Quadratic Unconstrained Optimization (QUBO) problems, recent studies show, that many combinatorial problems such as the TSP can be solved more efficiently in their native Polynomial Unconstrained Optimization (PUBO) forms. As many optimization problems in practice also contain continuous variables, our contribution investigates the performance of the QAOA in solving continuous optimization problems when using PUBO and QUBO formulations. Our extensive evaluation on suitable benchmark functions, shows that PUBO formulations generally yield better results, while requiring less qubits. As the multi-qubit interactions needed for the PUBO variant have to be decomposed using the hardware gates available, i.e., currently single- and two-qubit gates, the circuit depth of the PUBO approach outscales its QUBO alternative roughly linearly in the order of the objective function. However, incorporating the planned addition of native multi-qubit gates such as the global Molmer-Sorenson gate, our experiments indicate that PUBO outperforms QUBO for higher order continuous optimization problems in general

A cis-Acting Element in Retroviral Genomic RNA Links Gag-Pol Ribosomal Frameshifting to Selective Viral RNA Encapsidation

SummaryDuring retroviral RNA encapsidation, two full-length genomic (g) RNAs are selectively incorporated into assembling virions. Packaging involves a cis-acting packaging element (Ψ) within the 5′ untranslated region of unspliced HIV-1 RNA genome. However, the mechanism(s) that selects and limits gRNAs for packaging remains uncertain. Using a dual complementation system involving bipartite HIV-1 gRNA, we observed that gRNA packaging is additionally dependent on a cis-acting RNA element, the genomic RNA packaging enhancer (GRPE), found within the gag p1-p6 domain and overlapping the Gag-Pol ribosomal frameshift signal. Deleting or disrupting the two conserved GRPE stem loops diminished gRNA packaging and infectivity >50-fold, while deleting gag sequences between Ψ and GRPE had no effect. Downregulating the translation termination factor eRF1 produces defective virus particles containing 20 times more gRNA. Thus, only the HIV-1 RNAs employed for Gag-Pol translation may be specifically selected for encapsidation, possibly explaining the limitation of two gRNAs per virion

Inhibition of Both HIV-1 Reverse Transcription and Gene Expression by a Cyclic Peptide that Binds the Tat-Transactivating Response Element (TAR) RNA

The RNA response element TAR plays a critical role in HIV replication by providing a binding site for the recruitment of the viral transactivator protein Tat. Using a structure-guided approach, we have developed a series of conformationally-constrained cyclic peptides that act as structural mimics of the Tat RNA binding region and block Tat-TAR interactions at nanomolar concentrations in vitro. Here we show that these compounds block Tat-dependent transcription in cell-free systems and in cell-based reporter assays. The compounds are also cell permeable, have low toxicity, and inhibit replication of diverse HIV-1 strains, including both CXCR4-tropic and CCR5-tropic primary HIV-1 isolates of the divergent subtypes A, B, C, D and CRF01_AE. In human peripheral blood mononuclear cells, the cyclic peptidomimetic L50 exhibited an IC50 ∼250 nM. Surprisingly, inhibition of LTR-driven HIV-1 transcription could not account for the full antiviral activity. Timed drug-addition experiments revealed that L-50 has a bi-phasic inhibition curve with the first phase occurring after HIV-1 entry into the host cell and during the initiation of HIV-1 reverse transcription. The second phase coincides with inhibition of HIV-1 transcription. Reconstituted reverse transcription assays confirm that HIV-1 (−) strand strong stop DNA synthesis is blocked by L50-TAR RNA interactions in-vitro. These findings are consistent with genetic evidence that TAR plays critical roles both during reverse transcription and during HIV gene expression. Our results suggest that antiviral drugs targeting TAR RNA might be highly effective due to a dual inhibitory mechanism

Immediate Results of Percutaneous Trans-Luminal Mitral Commissurotomy in Pregnant Women with Severe Mitral Stenosis

Background Valvular heart diseases and mainly rheumatic heart diseases complicate about 1% of pregnancies. During pregnancy physiological hemodynamic changes of the circulation are the main cause of mitral stenosis (MS) decompensation. Prior to introduction of percutaneous mitral balloon commissuroplasty (PTMC), surgical comissurotomy was the preferred method of treatment in patients with refractory symptoms. PTMC is an established non-surgical treatment of rheumatic mitral stenosis. The study aimed to assess the safety and efficacy of PTMC in pregnant women with severs mitral stenosis. Material and Method Thirty three consecutive patients undergoing PTMC during pregnancy enrolled in this prospective study. Mitral valve area (MVA), transmitral valve gradient (MVG), and severity of mitral regurgitation (MR) were assessed before and 24 hour after the procedure by transthoracic and transesophageal echocardiography. Mitral valve morphology was evaluated before the procedure using Wilkin's criteria. Patient followed for one month and neonates monitored for weight and height and adverse effect of radiation. Result Mitral valve area increased from 0.83 ± 0.13 cm 2 to 1.38 ± 0.29 cm 2 ( P = 0.007). Mean gradient of mitral valve decreased from 15.5 ± 7.4 mmHg to 2.3 ± 2.3 mmHg ( P = <0.001). Pulmonary artery pressure decreased from 65.24 ± 17.9 to 50.45 ± 15.33 ( P = 0.012). No maternal death, abortion, intrauterine growth restriction was observed and only one stillbirth occurred. Conclusion PTMC in pregnant women has favorable outcome and no harmful effect on children noted

Interface circuit development and validation for hybrid piezoelectric-thermoelectric energy harvesters

Wireless sensor networks (WSNs) are critical components of sustainable operations in every major industry. First stage of the WSN in the figure can potentially be fully supported by renewable energy sources. Use of non-traditional ambient energy sources such as low frequency vibrations and temperature differences in the environment in a set of emerging embedded and smart applications, some of which designated in recent Horizon 2020 documents.Our group, which consists of members of MEMS Center at METU Ankara and REDAR (Renewable Energy Design and Applications Research) group at METU NCC, has been working on energy harvesting MEMS components and interface circuits required to support self-powered embedded sensors. In the next phase of this collaborated research, more comprehensive solutions need to be delivered using hybrid interfaces to simultaneously take advantage of multiple energy harvesting modes with outmost efficiency. An effective hybrid harvester that will power-up many embedded applications can take advantage of vibration and thermal resources in parallel using piezoelectric and thermoelectric conversion respectively. This research focuses on:•Efficient (60-100%) piezoelectric (PZT) interface circuit development with 2.5 µW minimum input power,•Efficient (20-50%) thermoelectric (TE) interface circuit development with 0.25 V minimum input voltage,•Compact, hybrid interface circuit development using above components for harvesting 100s of µWatts simultaneously

Piezoelektrik enerji üreteçleri için arayüz devresi tasarımı ve uygulaması.

Micro-fabricated piezoelectric transducer is a prominent harvesting method due to its small size and relatively high energy density. However, the available interface circuits (IC) in the literature for piezoelectric energy harvesters (PEH) are generally designed for macro-scaled versions having a power output in the range of hundreds µW. The efficiency of such systems is significantly diminished when input power drops to tens of µWs or less, which is the pertinent power output range for micro-fabricated devices. Therefore, it is necessary to develop efficient electronics to extract energy from low output power levels of Microelectromechanical systems (MEMS) piezoelectric energy harvesters. The main aim of this thesis is to develop ICs that can efficiently extract energy from the MEMS piezoelectric energy harvesters and charge storage element for powering up micro-electronic devices. In the first IC, a novel multi-stage energy extraction method is proposed to optimize the implementation of the synchronous electrical charge extraction (SECE) converter. This optimization allows downsizing of the external inductor without affecting the power-conversion efficiency. Then, a charge management approach is presented to speed up the charging of the large storage element. The advantage of this method is that it accelerates the transition from passive mode to active mode. Several circuit techniques are introduced to enhance practicability of the energy harvesting IC. An autonomous system is achieved through a start-up circuit with power management circuit that initiates the circuit from no primary charge. Implementations of active negative voltage converter and new ultra-low-power peak detector expand operating frequency range of the IC from 100 Hz to 4 kHz. Finally, self-adapting multi-stage energy extraction (MSEE) enhances power conversion efficiency for a wide input-power range. Maximum charging efficiency of 84 % is achieved with a 1 mH external inductor, while MEMS PEH is excited at 390 Hz. Second IC introduces a novel nonlinear switching technique aiming to boost extracted energy from low coupling factor PEHs and provide load-independent energy extraction with a single inductor. The idea is to enhance effective damping force of the PEH by processing piezoelectric voltage through a set of switches and an inductor. A novel maximum power point (MPP) sensing approach is proposed to achieve the optimal operation point of the proposed circuit regardless of input excitation level, for the first time in literature. The IC can efficiently harvest energy from shock vibrations, as MPP circuit adjusts optimal point regardless of the variation in the available energy on PEH. In the end, an efficient hybrid energy-harvesting interface is presented to simultaneously scavenge power from electromagnetic and piezoelectric sources, while driving a single load. The total simultaneously extracted power from both harvesters is more than the power obtained from each independently. The hybrid IC reaches up to 90% conversion efficiency with output power level of 100 µW. A wearable harvesting prototype consisting of custom-made electromagnetic harvester, off-the-shelf PEH, and the proposed interface circuit is built and tested to harvest energy from body movement.Ph.D. - Doctoral Progra

An Autonomous Interface Circuit Based on Self-Investing Synchronous Energy Extraction for Low Power Piezoelectric Energy Harvesters

This paper presents a self-powered interface circuit to rectify and manage the AC output of the piezoelectric energy harvesters (PEH) by utilizing Self-Investing Synchronous Electric Charge Extraction technique (SI-SECE). The system invests charges from the battery to PEH to improve the electromechanical coupling factor and consequently the energy extraction by utilizing only one external component. The circuit was implemented in 180 nm CMOS technology where high voltage (HV) MOS transistors are utilized to tolerate high open circuit output voltages of PEHs. MEMS PEH with 4.7 nF inherent capacitance has been used to charge a 1 mu F storage capacitor. Proposed interface circuit extracts 18.55 mu W that is 33 % more than traditional SECE (13.95 mu W) for 250 Hz PEH excitation frequency and 2.3 V piezoelectric open circuit voltage amplitude. At the output power of 48.5 mu W, maximum power conversion efficiency of 62.4% is achieved as charge investment and corresponding conduction and switching losses on investing transistors. SI-SECE delivers power with 4.5x relative performance improvement over on-chip full-bridge rectifier

An Unusual Biatrial Cardiac Myxoma in a Young Patient

This is a report of a biatrial cardiac myxoma in a young man with a 10-month history of exertional dyspnea and palpitation. The echocardiogram revealed biatrial myxoma prolapsing through the mitral and tricuspid valves during diastole. All cardiac chambers were enlarged and dysfunctional. The electrocardiogram revealed a rapid ventricular response with atrial flutter rhythm. The masses were resected and diagnosed as myxoma by a histological examination. The follow-up echocardiogram revealed significant improvement in ventricular function and reduction in the cardiac chambers’ volume. There was no evidence of myxoma recurrence. The most probable cause of the patient’s heart failure was considered to be tachycardia-induced cardiomyopathy