Transient Decay Research Articles

PO-01-124 THE CALCIUM HANDLING MACHINERY IS REMODELED IN FRIEDREICH’S ATAXIA

Friedreich's ataxia (FA) is an inherited neurodegenerative disorder that causes progressive nervous system damage. FA is caused by a deficiency in the frataxin protein due to an expansion of GAA repeats in the first intron of the frataxin gene. Reduced frataxin protein expression is thought to negatively affect mitochondrial function, leading to increased oxidative damage. Although FA is considered a neurodegenerative disorder, it is not completely understood why most patients present with left ventricular systolic dysfunction and die from cardiac events. The objective of our study is to determine whether the abnormal calcium handling machinery is a molecular mechanism that perpetuates cardiac dysfunction in FA. We used the frataxin knock-out (KO) mouse model of FA as well as human heart samples from donors with FA and from unaffected donors. The expression of calcium handling machinery proteins was assessed with proteomics and western blot. In left ventricular myocytes from KO and WT mice, the IonOptix system was used for calcium imaging, the seahorse assay was utilized to measure oxygen consumption rate (OCR) and confocal imaging was used to quantify the mitochondrial membrane potential (Δψm), and reactive oxygen species (ROS). ECG and echocardiography were used to assess cardiac function in the mice. In the proteomic analysis and western blot, SERCA2, Ryr2 and CaMKII were significantly downregulated, and the mitochondrial calcium handling proteins voltage-dependent anion channel and mitochondrial calcium uniporter were significantly upregulated in left ventricular tissue from humans with FA and from KO mice. On the ECG, the RR, PR, QRS, and QTc intervals were significantly longer in the KO mice. Echocardiography showed that the ejection fraction and fractional shortening were significantly decreased and left ventricular wall thickness and diameter were significantly increased in the KO mice. Moreover, the calcium transient decay was significantly prolonged in ventricular myocytes from KO mice compared to WT. Additionally, the Δψm was significantly depolarized, the OCR was significantly decreased, and ROS levels were significantly elevated in left ventricular myocytes from KO compared to WT. The development of left ventricular contractile dysfunction in FA is associated with reduced expression of calcium handling proteins, abnormal calcium cycling, and mitochondrial dysfunction.

Acellular hemoglobin impairs calcium release and contractility in cardiomyocytes from healthy animals

Hemoglobin (Hb)-based oxygen (O 2 ) carriers (HBOC) have been proposed as an alternative for blood transfusion. Phase III clinical trials of previous HBOC generations presented issues, such as vasoconstriction and myocardial infarction, that were not detected in pre-clinical trials. These problems have been attributed to extravasation of the low molecular weight (LMW) Hb species, nitric oxide (NO) scavenging and O 2 oversupply to the vasculature. However, the mechanisms responsible for the cardiac toxicity of HBOCs remain unclear. To explore the effects of acellular (acell) Hb and HBOC in cardiac tissues, we exposed cardiomyocytes (CMCs) to highly purified stroma-free acell bovine Hb (bHb) or human Hb (hHb). CMCs were loaded with Ca2+ fluorescent indicator (fluo-3) and put on laminin-coated coverslips. Cells were superfused with standard Tyrode solution with and without acell Hb. CMCs were stimulated with current pulses given at 1 Hz, and free cytosolic Ca2+ concentration was measured. To eliminate the effects of NO scavenging on CMCs, L-Name was added to the superfused with bHb and hHb. To study the effect of acell Hb MW on CMCs, LMW polymerized hHb (PolyhHb) was used to challenge CMCs. To explore the effect of Hb oxidation on CMCs, LMW MetHb was used to challenge the CMCs and compared to LMW PolyhMetHb. To explore the effects of antioxidants and heme toxicity, the studies with hHb and MethHb were repeated in the presence of the antioxidant N-acetylcysteine (NAC) or purified human Haptoglobin (Hp). Mitochondrial reactive oxygen species (ROS) production was measured using the fluorescent indicator MitoSOX Red after removing the Hb by washing the cells. After ROS determination, the maximal ROS production by CMCs was measured by challenging the cells with a high concentration of H 2 O 2 . Acell Hb increased the Ca 2+ transient decay time constant (tau) relative to control. Removing the effects of NO production with L-Name, increased the tau of the Ca 2+ transient in control and acell Hb challenge cells. Challenging CMCs with PolyhHb reduced the effects observed with acell Hb in Ca 2+ transients. MetHb appears to be worse than reduced Hb in terms of the changes induced to CMCs Ca 2+ transients. The antioxidant NAC mitigated the effects of acell Hb and MetHb but did not eliminate the changes on increased Ca2+ transients. The Hb scavenger, Hp, mitigated the effects of acell hHb and MethHb on Ca 2+ transients. The MitoSOX Red fluorescence was higher for CMCs exposed to acell Hb and MetHb compared to the control. PolyhHb and PolyMetHb challenge decreased the MitoSOX compared to acell hHb and MethHb. Cells with higher levels of ROS showed lower changes in fluorescence when exposed to H 2 O 2 . Here, we show that the toxicity of acell Hb is impart determined by facilitated diffusion, NO scavenging, heme release, and ROS, potentially affecting the energy supply and metabolism of CMCs. This study was supported by National Institutes of Health grants R01HL162120, R01HL159862 and the Department of Defense under grants W81XWH1810059. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Solid-state fluorophores featuring a combined hybridized local and charge transfer excited state and aggregation-induced emission as efficient emitters for electroluminescent devices

Solid-state fluorophores with high fluorescence efficiency and charge transportation have always been of great interest as emitters for organic light-emitting diodes (OLEDs). Mostly, donor (D)-acceptor (A) molecules holding prominent intramolecular charge transfer exhibit low fluorescence quantum yield. Here, we report a series of D–A–D type hybridized local and charge transfer (HLCT) excited state fluorophores (TBz, T2FBz, TFBz, TBBz, TPyBz, and TNz) containing benzo[c][1,2,5]thiadiazole (Bz) and its derivatives (5,6-difluoro-2,1,3-benzo[c][1,2,5]thiadiazole (2FBz), 5–2,1,3-benzo[c][1,2,5]thiadiazole (FBz), naphtho[1,2-c:5,6-c']bis([1,2,5]thiadiazole) (BBz), [1,2,5]thiadiazolo[3,4-c]pyridine (PyBz), and naphtho[2,3-c][1,2,5]thiadiazole (Nz)) as acceptor cores end-capped with tetraphenylethylene (TPE) as a donor and aggregation-induced emission (AIE)-luminogen. The different variations in the molecular structures of the cores render compounds with wide-ranging electronic and photophysical properties. The HLCT and AIE properties of these compounds are confirmed by theoretical calculations, solvatochromic behaviors, and transient decay lifetimes analyses. They show intense fluorescence emissions with good thermal stability and hole mobility, leading to effective utilization as emitters in OLEDs. The resulting devices demonstrate strong green to orange-red electroluminescent (EL) emissions with decent EL performance (Lmax of 6030–20220 cd m−1, CEmax of 6.26–13.18 cd A−1, and EQEmax of 3.51–5.11%). Among them, OLED fabricated with TBBz realized the best EL performance (Lmax of 11115 cd m−2, CEmax of, 12.03 cd A−1, EQEmax of 5.11%) with orange emission (λEL = 592 nm, CIE coordinates (0.53, 0.46)).

Examination of Trapping Effects on Single-Event Transients in GaN HEMTs

The effect of various trapping centers on single event-transients (SETs) in GaN high-electron-mobility transistors (HEMTs) are examined via calibrated technology computer aided design (TCAD) simulations. A single-channel, Schottky-gate HEMT computational model is developed and validated with static characteristics and single-photon absorption laser data. Simulations of SETs show that a two-dimensional electron gas (2DEG) enhancement effect occurs, which leads to additional collected charge in excess of the generated charge. The origins of this effect are examined and shown to result from an increase in occupation rate of the surface donor traps as the influx of charge is developed in the charge track. Variations in trap characteristics are then introduced and their effect on internal charge collection processes examined. It is further shown the SET response is dominated by the properties of the surface donor traps (i.e., energy level and density) such that the SET drain current closely follows the transient decay of occupation rate back to the original DC level.

11.2: The Effect of Doping Distribution on the Property of Green Phosphorescent Organic Light‐Emitting Diodes

In mass production OLED structures, doping ratio distribution across the thickness of emitting layer is not uniform owing to the linear evaporating configuration, where dopant and host materials are added in different sources. In this study, we firstly confirmed that different types of doping distribution among emitting layer of green phosphorescent OLED exhibited over 15% difference of current efficiency. By carefully designing and comparing emitting layers with a series of doping distribution modes, we found that dramatic variation of doping ratio near electron blocking layer was the critical factor. Then, trapping behavior of dopant molecules was confirmed to affect the carrier distribution among the emitting layer according to analysis of current density‐voltage (JV) and capacitance‐voltage (CV) curves from carrier only devices based on two types of doping distribution modes. Combining with the result of hole‐electron recombination zone (RZ), the area where possessed both high doping ratio and excitons recombination probability exhibited a high current efficiency and low driving voltage. Finally, PL and EL transient decay lifetime combined with triplet‐polaron quenching (TPQ) efficiency measurement demonstrated that TPQ was the main factor causing current efficiency difference between two types of doping distribution modes. Therefore, the doping distribution and trapping property of dopant material in emission layer should be carefully evaluated for OLED devices for mass production.

The near wake of discrete roughness elements on swept wings

This work presents the first experimental characterization of the flow field in the vicinity of periodically spaced discrete roughness elements (DRE) in a swept wing boundary layer. The time-averaged velocity fields are acquired in a volumetric domain by high-resolution dual-pulse tomographic particle tracking velocimetry. Investigation of the stationary flow topology indicates that the near-element flow region is dominated by high- and low-speed streaks. The boundary layer spectral content is inferred by spatial fast Fourier transform (FFT) analysis of the spanwise velocity signal, characterizing the chordwise behaviour of individual disturbance modes. The two signature features of transient growth, namely algebraic growth and exponential decay, are identified in the chordwise evolution of the disturbance energy associated with higher harmonics of the primary stationary mode. A transient decay process is instead identified in the near-wake region just aft of each DRE, similar to the wake relaxation effect previously observed in two-dimensional boundary layer flows. The transient decay regime is found to condition the onset and initial amplitude of modal crossflow instabilities. Within the critical DRE amplitude range (i.e. affecting boundary layer transition without causing flow tripping) the transient disturbances are strongly receptive to the spanwise spacing and diameter of the elements, which drive the modal energy distribution within the spatial spectra. In the super-critical amplitude forcing (i.e. causing flow tripping) the near-element stationary flow topology is dominated by the development of a high-speed and strongly fluctuating region closely aligned with the DRE wake. Therefore, elevated shears and unsteady disturbances affect the near-element flow development. Combined with the harmonic modes transient growth these instabilities initiate a laminar streak structure breakdown and a bypass transition process.

Modeling HTS non-insulated coils: A comparison between finite-element and distributed network models

High-temperature superconducting (HTS) non-insulated (NI) coils have the unique capability to bypass current through conductive turn-to-turn contacts, mitigating the possibility of a catastrophic failure in the event of a quench. However, this turn-to-turn conductivity leads to a significant increase in the coil decay/charging time constant. To understand this phenomenon, several modeling techniques have been proposed, including the lumped and distributed network (DN) circuit models, and more recently the finite-element (FE) models. In this paper, the decay results obtained from modeling HTS NI pancake coils using both a DN model and a 2D FE model approach are evaluated and compared. Steady-state fields, and transient charging and decay behaviors are calculated with each model and the results compared. Key differences are highlighted, including the computation speed and the capturing of various physical phenomena. Both models exhibit non-exponential decay during initial coil discharge due to current redistribution between the inner and outer turns. In addition, the FE model exhibits other effects arising from current redistribution in both the radial and axial directions, including remanent magnetization, and variation of the “apparent total inductance” during charging. Simulations of sudden discharge have also been analyzed using the common “lumped circuit” formula. This shows that extracted values for the apparent surface contact resistance between coil windings can differ by more than a factor of 5 from the initial input value. Our results confirms the optimal choice of architecture for future NI coil models and emphasize that caution should be exercised when interpreting experimental results using the lumped circuit approach.

Improved Crystallization of Lead Halide Perovskite in Two-Step Growth Method by Polymer-Assisted "Slow-Release Effect".

Fast reaction between organic salt and lead iodide always leads to small perovskite crystallites and concentrated defects. Here, polyacrylic acid is blended with organic salt, so as to regulate the crystallization in a two-step growth method. It is observed that addition of polyacrylic acid retards aggregation and crystallization behavior of the organic salt, and slows down the reaction rate between organic salt and PbI2 , by which "slow-release effect" is defined. Such effect improves crystallization of perovskite. X-ray diffraction study shows that, after addition of 2mm polyacrylic acid, average crystallite size of perovskite increases from ≈40 to ≈90nm, meanwhile, grain size increases. Thermal admittance spectroscopy study shows that trap density is reduced by nearly one order (especially for deep energy levels). Due to the improved crystallization and reduced trap density, charge recombination is obviously reduced, while lifetime of charge carriers in perovskite film and devices are prolonged, according to time-resolved photoluminescence and transient photo-voltage decay curve tests, respectively. Accordingly, power conversion efficiency of the device is promoted from 19.96 (±0.41)% to 21.84 (±0.25)% (with a champion efficiency of 22.31%), and further elevated to 24.19% after surface modification by octylammonium iodide.

Decay of Raman active vibrations within oxide groups of potassium titanyl phosphate

Decay of nine Raman active vibrations assigned to TiO6− and PO4− oxide groups of KTiOPO4 nonlinear-optical-gain crystal have been directly traced in time with <120 fs resolution. Coherent Anti-Stokes Raman scattering technique with three-color tunable femtosecond pulses provided detection of phonon decay transients with up to 70 dB signal spans and resulted in the equivalent spectral resolution of better than 0.15 cm−1. The equilibrium phonon decay rates ranged between 0.93 and 4.25 ps−1 yielding in the corresponding linewidths of 4.9–22.3 cm−1 for the homogeneously broadened vibrations.

Critical Link between Calcium Regional Heterogeneity and Atrial Fibrillation Susceptibility in Sheep Left Atria.

Atrial fibrillation is the most sustained form of arrhythmia in the human population that leads to important electrophysiological and structural cardiac remodeling as it progresses into a chronic form. Calcium is an established key player of cellular electrophysiology in the heart, yet to date, there is no information that maps calcium signaling across the left atrium. The aim of this study is to determine whether calcium signaling is homogenous throughout the different regions of the left atrium. This work tests the hypothesis that differences across the healthy left atrium contribute to a unique, region-dependent calcium cycling and participates in the pro-arrhythmic activity during atrial fibrillation. An animal model relevant to human cardiac function (the sheep) was used to characterize both the electrical activity and the calcium signaling of three distinct left atrium regions (appendage, free wall and pulmonary veins) in control conditions and after acetylcholine perfusion (5 μM) to induce acute atrial fibrillation. High-resolution dual calcium-voltage optical mapping on the left atria of sheep was performed to explore the spatiotemporal dynamics of calcium signaling in relation to electrophysiological properties. Action potential duration (at 80% repolarization) was not significantly different in the three regions of interest for the three pacing sites. In contrast, the time to 50% calcium transient decay was significantly different depending on the region paced and recorded. Acetylcholine perfusion and burst pacing-induced atrial fibrillation when pulmonary veins and appendage regions were paced but not when the free wall region was. Dantrolene (a ryanodine receptor blocker) did not reduce atrial fibrillation susceptibility. These data provide the first evidence of heterogenous calcium signaling across the healthy left atrium. Such basal regional differences may be exacerbated during the progression of atrial fibrillation and thus play a crucial role in focal arrhythmia initiation without ryanodine receptor gating modification.

WO3-NP-activated WS2 layered heterostructures for efficient broadband (254 nm-940 nm) photodetection.

Broadband photodetection including deep UV using Si is technically challenging due to its negligible optical absorption at 254 nm and the requirement of heterogeneous integration with very high bandgap photoactive materials. However, monolithic integration of high-bandgap semiconductors on Si is not possible due to CMOS fabrication incompatibility. Comprehensive experimental studies to achieve broadband photodetection including deep UV on Si are lacking in the literature. Here for the first time we have investigated 2D/0D heterojunctions of WS2/WO3 on a Si platform both experimentally and theoretically and established the charge transfer mechanism between them. Transient photocarrier decay experiments demonstrate effective quenching of excited photocarriers generated in WO3/WS2, signifying its utility in facilitating carrier transport, which is further evidenced by charge density calculation from DFT simulation. Our designed vertically aligned p-Si/WS2/WO3 heterojunction-based photodetector exhibits an excellent photosensitivity performance with a broad spectral response ranging from deep ultraviolet (254 nm) to near infrared (940 nm) wavelengths, and it not only provides a peak responsivity of 251 A W-1 and a specific detectivity of 1.89 × 014 Jones, but also possesses a rapid response speed with a rise/fall time of 0.64/0.48 s at 365 nm with a bias of 2 volt.

State-selective probing of CO2 autoionizing inner valence Rydberg states with attosecond extreme ultraviolet four-wave-mixing spectroscopy

Nonlinear spectroscopies can disentangle spectra that are congested due to inhomogeneous broadening. In conjunction with theoretical calculations, attosecond extreme ultraviolet (XUV) four-wave-mixing (FWM) spectroscopy is utilized here to probe the dynamics of autoionizing inner valence excited Rydberg states of the polyatomic molecule, ${\mathrm{CO}}_{2}$. This tabletop nonlinear technique employs a short attosecond XUV pulse train and two noncollinear, few-cycle near-infrared pulses to generate background-free XUV wave-mixing signals. FWM emission is observed from the $n=5--7$ states of the Henning sharp $nd{\ensuremath{\sigma}}_{g}$ Rydberg series that converges to the ionic $\stackrel{\ifmmode \tilde{}\else \~{}\fi{}}{B}\phantom{\rule{4pt}{0ex}}^{2}\mathrm{\ensuremath{\Sigma}}_{u}^{+}$ state. However, these transient emission signals decay with lifetimes of 33 $\ifmmode\pm\else\textpm\fi{}$ 6, 53 $\ifmmode\pm\else\textpm\fi{}$ 2, and 94 $\ifmmode\pm\else\textpm\fi{}$ 2 fs, respectively, which calculations show are consistent with the lifetimes of the short-lived $n=6--8$ members of the $ns{\ensuremath{\sigma}}_{g}$ character Henning diffuse Rydberg series. The oscillator strengths of transitions between states involved in all possible resonant FWM processes are calculated, verifying that the nonlinear spectra are dominated by pathways described by an initial excitation to the diffuse $ns{\ensuremath{\sigma}}_{g}$ Rydberg series and emission from the sharp $nd{\ensuremath{\sigma}}_{g}$ Rydberg series. The results substantiate not only that attosecond XUV FWM spectroscopy produces rigorous and meaningful measurements of ultrafast dynamics in polyatomic systems, but also that nonlinear spectroscopic techniques are versatile tools to selectively probe dynamics that are otherwise difficult to access.

Continuation analysis of overhung rotor bouncing cycles with smooth and contact nonlinearities

Time simulation has been widely used when investigating the nonlinear response of rotating machines, due to its relative simplicity. However, this approach is computationally inefficient due to large transient decay times and the need to repeat the analysis for multiple drive speeds and initial conditions, and is incomplete because of its inability to give information about unstable responses. Alternatively, the numerical continuation method can be used to explore the nonlinear behaviour of such systems in a more systematic and efficient way. In rotating machinery, tighter tolerances are valued for efficiency, making the rotor–stator contact phenomenon a priority for research. Various cases including rigid and very compliant contact stiffness models have been investigated in the literature, in many cases showing responses similar to that of smooth nonlinearities such as cubic stiffness. This knowledge has been used in the present study to transform the bifurcation diagram of a simpler nonlinearity (cubic) to a more complex one (contact represented by bilinear stiffness approximated using a tanh formulation) through a homotopy of the nonlinear restoring forces present in the system definition. A 2-dof overhung rotor with gyroscopic effects is used in the investigation of quasiperiodic bouncing cycles that appear periodic in the rotating frame. This work not only provides more insight into the behaviour of nonlinear rotor–stator contact responses, but also demonstrates the numerical continuation method as a potential tool to explore the nonlinear rotating system’s response in a more structured manner.

Investigation of the surface recombination rate in polycrystalline films from the A6B6 compound by the MW-PC method

In this article, the surface recombination rates in polycrystalline CdTe films obtained on oxidized substrates are studied. The results of the corona discharge effect on the CdTe-SiO2–Si-Al structure are presented. In this case, in the static mode, a shift of the short-circuit current spectra to the short-wave region was observed. To analyze the shift of the short-circuit current spectra, the method of microwave probe photoconductivity (MW-PC) was used and non-contact registration of decay transients for excess carriers was carried out. Considering that for CdTe in the wavelength range of about 800–1000 nm, the absorption coefficient increases sharply with the excitation photon energy at the absorption edge. It was found that the surface recombination rate was estimated at 19 ns. It has been determined that the filling of surface traps in CdTe leads to a decrease in the effect of surface recombination.

Diabetes and Excess Aldosterone Promote Heart Failure With Preserved Ejection Fraction.

Background The pathobiology of heart failure with preserved ejection fraction (HFpEF) is still poorly understood, and effective therapies remain limited. Diabetes and mineralocorticoid excess are common and important pathophysiological factors that may synergistically promote HFpEF. The authors aimed to develop a novel animal model of HFpEF that recapitulates key aspects of the complex human phenotype with multiorgan impairments. Methods and Results The authors created a novel HFpEF model combining leptin receptor-deficient db/db mice with a 4-week period of aldosterone infusion. The HFpEF phenotype was assessed using morphometry, echocardiography, Ca2+ handling, and electrophysiology. The sodium-glucose cotransporter-2 inhibitor empagliflozin was then tested for reversing the arrhythmogenic cardiomyocyte phenotype. Continuous aldosterone infusion for 4 weeks in db/db mice induced marked diastolic dysfunction with preserved ejection fraction, cardiac hypertrophy, high levels of B-type natriuretic peptide, and significant extracardiac comorbidities (including severe obesity, diabetes with marked hyperglycemia, pulmonary edema, and vascular dysfunction). Aldosterone or db/db alone induced only a mild diastolic dysfunction without congestion. At the cellular level, cardiomyocyte hypertrophy, prolonged Ca2+ transient decay, and arrhythmogenic action potential remodeling (prolongation, increased short-term variability, delayed afterdepolarizations), and enhanced late Na+ current were observed in aldosterone-treated db/db mice. All of these arrhythmogenic changes were reversed by empagliflozin pretreatment of HFpEF cardiomyocytes. Conclusions The authors conclude that the db/db+aldosterone model may represent a distinct clinical subgroup of HFpEF that has marked hyperglycemia, obesity, and increased arrhythmia risk. This novel HFpEF model can be useful in future therapeutic testing and should provide unique opportunities to better understand disease pathobiology.

Modulation of Mitochondrial Bioenergetics by Polydopamine Nanoparticles in Human iPSC-Derived Cardiomyocytes.

Myocardial infarction (MI) leads to the formation of an akinetic scar on the heart muscle causing impairment in cardiac contractility and conductance, leading to cardiac remodeling and heart failure (HF). The current pharmacological approaches for attenuating MI are limited and often come with long-term adverse effects. Therefore, there is an urgent need to develop novel multimodal therapeutics capable of modulating cardiac activity without causing any major adverse effects. In the current study, we have demonstrated the applicability of polydopamine nanoparticles (PDA-NPs) as a bioactive agent that can enhance the contractility and beat propagation of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Treatment of hiPSC-CMs with PDA-NPs demonstrated accumulation of the latter into mitochondria and significantly enhanced time-dependent adenosine triphosphate (ATP) production in these cells, indicating improved mitochondrial bioenergetics. Furthermore, the effect of PDA-NPs on hiPSC-CM activity was evaluated by measuring calcium transients. Treatment with PDA-NPs increased the calcium cycling in hiPSC-CMs in a temporal manner. Our results demonstrated a significant reduction in peak amplitude, transient duration, time to peak, and transient decay time in the PDA-NPs-treated hiPSC-CMs as compared to untreated hiPSC-CMs. Additionally, treatment of isolated perfused rat heart ex vivo with PDA-NPs demonstrated cardiotonic effects on the heart and significantly improved the hemodynamic function, suggesting its potential for enhancing whole heart contractility. Lastly, the gene expression analysis data revealed that PDA-NPs significantly upregulated cardiac-specific genes (ACADM, MYL2, MYC, HCN1, MYL7, GJA5, and PDHA1) demonstrating the ability to modulate genetic expression of cardiomyocytes. Taken together, these findings suggest PDA-NPs capability as a versatile nanomaterial with potential uses in next-generation cardiovascular applications.

Thermal control of oxygen-induced emission states in carbon dots for indoor lighting applications

Understanding the role of heteroatoms in carbon dots (CDs) has been recognized as a critical factor for the design and engineering of their optical properties. Oxygen is one of the most prevalent heteroatom defects in CDs; however, its effects on the optical properties are still unclear because it has not been possible to precisely control the degree of oxidation of CDs. Here, we report the synthesis of CDs in a controlled process that allows thermal control of the oxygen content using benzyl alcohol as an oxidizing solvent. The results suggest that oxygen-induced defects reduce the optical band gap of CDs, and their emission is red-shifted from blue (428 nm) to red (628 nm). The photoexcited charge-carrier dynamics of the CDs were thoroughly studied using transient absorption spectroscopy and fluorescence decay measurements. Furthermore, the bright multicolored emission of our CDs renders them suitable for sun-like panchromatic indoor lighting applications. We believe that these new insights into oxygen-induced defects in CDs will result in significant progress in their practical use.

Nitrosylation of cardiac CaMKII at Cys290mediates mechanical afterload-induced increases in Ca2+ transient and Ca2+ sparks.

Cardiac mechanical afterload induces an intrinsic autoregulatory increase in myocyte Ca2+ dynamics and contractility to enhance contraction (known as the Anrep effect or slow force response). Our prior work has implicated both nitric oxide (NO) produced by NO synthase 1 (NOS1) and calcium/calmodulin-dependent protein kinase II (CaMKII) activity as required mediators of this form of mechano-chemo-transduction. To test whether a single S-nitrosylation site on CaMKIIδ (Cys290) mediates enhanced sarcoplasmic reticulum Ca2+ leak and afterload-induced increases in sarcoplasmic reticulum (SR) Ca2+ uptake and release, we created a novel CRISPR-based CaMKIIδ knock-in (KI) mouse with a Cys to Ala mutation at C290. These CaMKIIδ-C290A-KI mice exhibited normal cardiac morphometry and function, as well as basal myocyte Ca2+ transients (CaTs) and β-adrenergic responses. However, the NO donor S-nitrosoglutathione caused an acute increased Ca2+ spark frequency in wild-type (WT) myocytes that was absent in the CaMKIIδ-C290A-KI myocytes. Using our cell-in-gel system to exert multiaxial three-dimensional mechanical afterload on myocytes during contraction, we found that WT myocytes exhibited an afterload-induced increase in Ca2+ sparks and Ca2+ transient amplitude and rate of decline. These afterload-induced effects were prevented in both cardiac-specific CaMKIIδ knockout and point mutant CaMKIIδ-C290A-KI myocytes. We conclude that CaMKIIδ activation by S-nitrosylation at the C290site is essential in mediating the intrinsic afterload-induced enhancement of myocyte SR Ca2+ uptake, release and Ca2+ transient amplitude (the Anrep effect). The data also indicate that NOS1 activation is upstream of S-nitrosylation at C290 of CaMKII, and that this molecular mechano-chemo-transduction pathway is beneficial in allowing the heart to increase contractility to limit the reduction in stroke volume when aortic pressure (afterload) is elevated. KEY POINTS: A novel CRISPR-based CaMKIIδ knock-in mouse was created in which kinase activation by S-nitrosylation at Cys290 (C290A) is prevented. How afterload affects Ca2+ signalling was measured in cardiac myocytes that were embedded in a hydrogel that imposes a three-dimensional afterload. This mechanical afterload induced an increase in Ca2+ transient amplitude and decay in wild-type myocytes, but not in cardiac-specific CaMKIIδ knockout or C290A knock-in myocytes. The CaMKIIδ-C290 S-nitrosylation site is essential for the afterload-induced enhancement of Ca2+ transient amplitude and Ca2+ sparks.

Nanosheets of In2S3/S-C3N4-Dots for Solar Water-Splitting in Saline Water.

Hydrogen generation from splitting of water under the photoelectrochemical (PEC) pathway is considered as the most promising strategy for covering the upcoming fuel crisis by taking care of all environmental issues. In this context, In2S3 can be explored as it is a visible light-active semiconductor with an appropriate band alignment with the water redox potential. Herein, In2S3 nanosheets are developed by the chemical method. The nanosheets of In2S3 absorb high visible light due to the manifold inside scattering and reflection. The PEC activity of In2S3 is enhanced because of the increase in the light absorbance of the materials. In the present work, at 1.18 V versus RHE in 3.5 wt % NaCl, a maximum 2.07 mA/cm2 photocurrent density can be achieved by In2S3 nanosheets. However, In2S3 suffers strongly due to photo-corrosion. To improve the efficacy of the In2S3 nanosheets in saline water, the charge-carrier transportation ability of In2S3 is aimed to increase by decorating S-C3N4-dots on In2S3. The heterostructure of type-II is developed by sensitization of S-C3N4-dots on In2S3. It increases both the transportation of charge carriers as well as separation. In the heterostructure, the transient decay time (τ) increases, which indicates a decrease in photogenerated charge-carrier recombination. S-C3N4-dots also act as an optical antenna and increase the range of visible light absorbance of In2S3. The heterostructure can generate ∼2.38-fold higher photocurrent density of 1.18 V versus RHE in 3.5 wt % NaCl. The photoconversion efficiency of the heterostructure is 0.88% at 0.95 V versus RHE. The nanosheets of In2S3 and In2S3/S-C3N4-dots are stable, and photocurrent density is measured up to 2700 s under continuous back-illumination conditions.

(Invited, Digital Presentation) ML-Based Fast on-Chip Transient Thermal Simulation for Heterogeneous 2.5D/3D IC Designs

Large 3DIC designs with multiple chips requireseveral iterations of transient thermal analysis particularly forfine-grain on-chip dynamic thermal management. This requiresa fast thermal analysis technology as opposed to traditionalCFD/FEA based methods which have severe runtime/capacitylimitations for large chips (e.g., 2cmx2cm) in 3DIC whilegenerating fine grained (e.g., 10umx10um) transient thermalresponse. The fast transient thermal analysis is based on the ideaof combining the global, intermediate, and local transientresponse curves generated from an ML-predictor. The local,intermediate, and global transient response curves are scaledbased on the far-field and near-field transient decay surfacecomponents respectively, computed using the trained ML decaysurface predictor, followed by linear superposition of the curvesfor each power value in the transient power profile to generatethe effective transient response curve. The runtime forgenerating thermal results for a large chip is in the order ofminutes, compared to several hours/days while using CFD/FEAbased tools with good accuracy correlation. The fast transientthermal solver is implemented on distributed ML computingplatform for parallel computation of transient thermal inferencemodel.