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Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation
Highlights: • NLRR3 is a membrane protein highly expressed in favorable neuroblastoma. • NLRR3-ICD was produced through proteolytic processing by secretases. • NLRR3-ICD was induced to be translocated into cell nucleus following ATRA exposure. • NLRR3-ICD plays a pivotal role in ATRA-mediated neuroblastoma differentiation. - Abstract: We have previously identified neuronal leucine-rich repeat protein-3 (NLRR3) gene which is preferentially expressed in favorable human neuroblastomas as compared with unfavorable ones. In this study, we have found for the first time that NLRR3 is proteolytically processed by secretases and its intracellular domain (NLRR3-ICD) is then released to translocate into cell nucleus during ATRA-mediated neuroblastoma differentiation. According to our present observations, NLRR3-ICD was induced to accumulate in cell nucleus of neuroblastoma SH-SY5Y cells following ATRA treatment. Since the proteolytic cleavage of NLRR3 was blocked by α- or γ-secretase inhibitor, it is likely that NLRR3-ICD is produced through the secretase-mediated processing of NLRR3. Intriguingly, forced expression of NLRR3-ICD in neuroblastoma SK-N-BE cells significantly suppressed their proliferation as examined by a live-cell imaging system and colony formation assay. Similar results were also obtained in neuroblastoma TGW cells. Furthermore, overexpression of NLRR3-ICD stimulated ATRA-dependent neurite elongation in SK-N-BE cells. Together, our present results strongly suggest that NLRR3-ICD produced by the secretase-mediated proteolytic processing of NLRR3 plays a crucial role in ATRA-mediated neuronal differentiation, and provide a clue to develop a novel therapeutic strategy against aggressive neuroblastomas.
Role of cardiac {sup 123}I-mIBG imaging in predicting arrhythmic events in stable chronic heart failure patients with an ICD
Background: Despite therapeutic improvement, the prognosis of chronic heart failure (CHF) remains unfavorable partly due to arrhythmia and sudden cardiac death (SCD). This prospective study evaluated myocardial {sup 123}I-meta-iodobenzylguanidine ({sup 123}I-mIBG) scintigraphy as a predictor of arrhythmic events (AE) in CHF patients. Methods: 170 CHF patients referred for implantable cardioverter-defibrillator (ICD) implantation for both primary and secondary prevention were enrolled. All patients underwent planar and SPECT imaging. Early and late heart-to-mediastinum (H/M) ratio, {sup 123}I-mIBG washout (WO), early and late summed SPECT scores were calculated The primary endpoint was an AE: sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate ICD therapy or SCD. The secondary endpoint was appropriate ICD therapy. Results: During a median follow-up of 23.3 months, 69 patients experienced an AE. Early summed score (ESS) was the only independent predictor of AE [HR 1.023 (1.003-1.043)]. Focussing on only patients with an ICD for primary prevention, ESS was the only independent predictor of AE [HR 1.028 (1.007-1.050)]. {sup 123}I-mIBG-derived parameters failed to be independent predictors of appropriate ICD therapy. However there was a “bell-shaped” relation between {sup 123}I-mIBG scintigraphy-derived parameters and AE and appropriate ICD therapy, i.e., those with intermediate {sup 123}I-mIBG abnormalities tended to be at higher risk of events. Conclusion: Although SPECT {sup 123}I-mIBG scintigraphy was associated with AE in CHF patients with ICD implantation for primary and secondary prevention, no association was found between {sup 123}I-mIBG scintigraphy-derived parameters and appropriate ICD therapy.
T wave alternans as a predictor of recurrent ventricular tachyarrhythmias in ICD recipients: prospective comparison with conventional risk markers
INTRODUCTION: The current standard for arrhythmic risk stratification is electrophysiologic (EP) testing, which, due to its invasive nature, is limited to patients already known to be at high risk. A number of noninvasive tests, such as determination of left ventricular ejection fraction (LVEF) or heart rate variability, have been evaluated as additional risk stratifiers. Microvolt T wave alternans (TWA) is a promising new risk marker. Prospective evaluation of noninvasive risk markers in low- or moderate-risk populations requires studies involving very large numbers of patients, and in such studies, documentation of the occurrence of ventricular tachyarrhythmias is difficult. In the present study, we identified a high-risk population, recipients of an implantable cardioverter defibrillator (ICD), and prospectively compared microvolt TWA with invasive EP testing and other risk markers with respect to their ability to predict recurrence of ventricular tachyarrhythmias as documented by ICD electrograms. METHODS AND RESULTS: Ninety-five patients with a history of ventricular tachyarrhythmias undergoing implantation of an ICD underwent EP testing, assessment of TWA, as well as determination of LVEF, baroreflex sensitivity, signal-averaged ECG, analysis of 24-hour Holter monitoring, and QT dispersion from the 12-lead surface ECG. The endpoint of the study was first appropriate ICD therapy for electrogram-documented ventricular fibrillation or tachycardia during follow-up. Kaplan-Meier survival analysis revealed that TWA (P < 0.006) and LVEF (P < 0.04) were the only significant univariate risk stratifiers. EP testing was not statistically significant (P < 0.2). Multivariate Cox regression analysis revealed that TWA was the only statistically significant independent risk factor. CONCLUSIONS: Measurement of microvolt TWA compared favorably with both invasive EP testing and other currently used noninvasive risk assessment methods in predicting recurrence of ventricular tachyarrhythmias in ICD recipients. This study suggests that TWA might also be a powerful tool for risk stratification in low- or moderate-risk patients, and needs to be prospectively evaluated in such populations.
Atmospheric, Magnetospheric and Plasmas in Space (AMPS) spacelab payload definition study. Volume 3: Interface control documents. Part 2: AMPS payload to spacelab ICD
The AMPS to Spacelab Interface Control Document which is to be used as a guide for format and information content in generating specific AMPS Mission ICDs is presented. This document is meant to supplement the Spacelab Payload Accommodations Handbook in that it only defines interfaces which are not discussed in the handbook to the level required for design purposes. The AMPS Top Level Requirements Tree, illustrates this ICD by a shaded area and its relationship to the other AMPS technical documents. Other interface documents shown are the Level II, AMPS to Space Shuttle Vehicle ICD and the Level III, AMPS to Instruments ICD.
Ab initio calculation of ICD widths in photoexcited HeNe
Excitation of HeNe by synchrotron light just below the frequency of the 1s → 3p transition of isolated He has been recently shown to be followed by resonant interatomic Coulombic decay (ICD). The vibrationally resolved widths of the ICD states were extracted with high precision from the photoion spectra. In this paper, we report the results of ab initio calculations of these widths. We show that interaction between electronic states at about the equilibrium distance of HeNe makes dark states of He accessible for the photoexcitation and subsequent electronic decay. Moreover, the values of the calculated widths are shown to be strongly sensitive to the presence of the non-adiabatic coupling between the electronic states participating in the decay. Therefore, only by considering the complete manifold of interacting decaying electronic states a good agreement between the measured and computed ICD widths can be achieved.
Live Virtual Constructive (LVC): Interface Control Document (ICD) for the LVC Gateway
This Interface Control Document (ICD) documents and tracks the necessary information required for the Live Virtual and Constructive (LVC) systems components as well as protocols for communicating with them in order to achieve all research objectives captured by the experiment requirements. The purpose of this ICD is to clearly communicate all inputs and outputs from the subsystem components.
Apollo Intercenter ICD Management Procedure - Apollo Program
Apollo program intercenter ICD management procedure
External Wireless Communications (EWC) Coverage Expansion Boom Interface Control Document (ICD)
This document defines and controls the physical and functional interfaces between the External Wireless Communications Coverage Expansion (EWCCE) boom and any payload that is planned to be installed on the scarred locations on the boom. The hardware will be referenced as EWCCE boom or simply boom in this document. The boom is comprised of two short boom sections,the upper boom and the lower boom, an Active Worksite Interface (AWIF) and two mounting plates. The boom will be launched soft stowed in a bag and assembled in the Internation Space Station (ISS) via IVA. The assembly will include two sections of the boom and a built-to-print AWIF. The installation of the final assembly to the ISS Truss location is designated as a free-float EVA worksite activity. Once installed on the truss, the interfaces on the Long Boom may be used for attachment of future Orbital Replacement Units (ORUs) to either the Television Camera (TVC) Mounting Slide interface (e.g., an External High Definition Camera [EHDC] or similar ORU) or to future On-orbit Installed Hand-rails (OIHs) installed at the seat track interfaces. Compliance with this Interface Control Document (ICD) will ensure compatibility and successful integration of the hardware.
Iodine-123-metaiodobenzylguanidine cardiac SPECT imaging in the qualification of heart failure patients for ICD implantation
No abstract prepared.
The impact of proposed changes to ICD-11 on estimates of PTSD prevalence and comorbidity
Not Available
iHiFi Project/Task LANL Lower S-Band Power Amp Baseline ICD Data [Slides]
Abstract not provided.
Nanosecond Gated CMOS Camera (NSGCC) ICD (Rev. 2.1)
The Ultra-Fast X-ray Imager (UXI) program is an ongoing effort at Sandia National Laboratories to create high speed, multi-frame, time-gated Read Out Integrated Circuits (ROICs), and a corresponding suite of photodetectors to image a wide variety of High Energy Density (HED) physics experiments on both Sandia’s Z-Machine and LLNL’s National Ignition Facility (NIF). Several cameras have been designed over the length of the program; one of the most recent is the Icarus, which is an improvement on past imagers (Furi and Hippogriff). A second sensor that can be connected is the Daedalus sensor. The Icarus is a 1024 × 512-pixel array with either 25 μm or 8 µm spatial resolution containing four frames of storage per pixel and has improved timing generation and distribution components while achieved 2 ns time gating. The Daedalus sensor is also a 1024 x 512-pixel array with 25 µm special resolution containing three frames of storage per pixel and has an increased set of features for a wider variety of applications from interlacing of rows in each frame to configurability of all shutters. See Section 14 for details regarding the Icarus implementation of the firmware and Section 15 for details regarding the Daedalus implementation. Due to the unique test environments UXI sensors are targeted for, full custom hardware was required to physically mount an Icarus or Daedalus sensor, manage its various functions, and read out pixel data for transfer to a host computer. Beyond experimental functionality, the hardware also needed to accommodate sensor characterization requirements. Lawrence Livermore National Laboratory’s ‘Version 4.0 Board’ was the result of these efforts. It mounts all the components required to fully utilize the Icarus and Daedalus sensors including analog to digital converters to convert pixel data and various system voltages to digital form for readout and analysis, DAC channels for remote configuration of critical bias voltages, static random-access memories to buffer pixel data, RS422 and Gigabit Ethernet communications for remote access, and an FPGA to tie these components together. This document describes the FPGA electrical interfaces in detail to allow the reader a greater understanding of the device, and to facilitate implementation of custom software to control and manage it. The Version 4.0 Board is a continuation of the Nano-second Gated CMOS hardware design that retains much of the functionality of the Version 1.0 Board while adding features including a DAC instead of digital potentiometers, as well as sensors for pressure and radiation. The Version 4.0 board is intended for applications requiring tight form-factor enclosures. It is composed of two stacking boards; one holds the FPGA and regulators to power the various components of the board while the other contains the mating connector to the sensor, image-readoff ADCs, the DAC, and other components.
Atmospheric, Magnetospheric and Plasmas in Space (AMPS) spacelab payload definition study. Volume 3: Interface control documents. Part 1: AMPS payload to shuttle ICD
Physical, functional, and operational interfaces between the space shuttle orbiter and the AMPS payload are described for the ground handling and test phases, prelaunch, launch and ascent, operational, stowage, and reentry and landing activities.
Atmospheric, Magnetospheric and Plasmas in Space (AMPS) spacelab payload definition study. Volume 3: Interface control documents. Part 3: AMPS payload to instruments ICD
General physical, functional, and operational interface control requirements for instruments on the first AMPS payload are presented. Interface specifications are included to satisfy ground handling, prelaunch, launch, stowage, operation, and landing activities. Applicable supporting documentation to implement the information is also given.
Atmosphere, Magnetosphere and Plasmas in Space (AMPS). Spacelab payload definition study. Volume 3; book 1: AMPS equipment to orbiter ICD
The physical, thermal, and electrical interfaces that exist between Spacelab-AMPS Payload No.(TBD) and the orbiter are described.
Atmosphere, Magnetosphere and Plasmas in Space (AMPS). Spacelab payload definition study. Volume 3, book 2: AMPS equipment to Spacelab ICD
The interfaces between AMPS Payload No.(TBD) and Spacelab are described. The interfaces specified cover the AMPS physical, electrical, and thermal interfaces that are established to prescribe the standard Spacelab configuration required to perform the mission. If the configuration definition changes due to change of Spacelab equipment model, or serial numbers, then reidentification of the Labcraft payload may be required.