Pulse Protocol Research Articles

Pulsed exposure toxicity testing: Baseline evaluations and considerations using copper and zinc with two marine species

Methods to assess environmental impacts from episodic discharges on receiving water bodies need a more environmentally relevant and scientifically defensible toxicity test design. Many permittees are regularly required to conduct 96-h toxicity tests on discharges associated with events that are generally less than 24 h in duration. Current standardized methods do not adequately reflect these episodic discharge conditions at either the point of compliance nor as it mixes with the receiving environment. In order to evaluate more representative biological effects, an alternative toxicity approach is described incorporating pulsed exposures of effluents and subsequent transfer of test organisms to clean water for the remainder of the test. This pulsed exposure protocol incorporates a slight modification to USEPA Whole Effluent Toxicity (WET) chronic and acute methods for two marine species, purple sea urchin embryos, Strongylocentrotus purpuratus, and juvenile mysid shrimp Americamysis bahia. Tests were performed with toxicants using standard static (96 h) and pulsed (6, 12, and 26 h) exposures. Following pulsed exposures, organisms were transferred to uncontaminated seawater for the remainder of the 96-h test period. Results for these species and endpoints indicated that the sensitivity of these species to copper and zinc were up to two orders of magnitude greater using standard continuous exposures compared to shorter pulsed exposures. Additional considerations assessed included timing of the onset of a pulse and latent effects following an exposure. This modified approach requires minimal modification to current standard methods and increases the realism to more accurately assess toxic effects resulting from episodic discharges.

Gene transfer by electroporation with high frequency bipolar pulses in vitro

High-frequency bipolar pulses (HF-BP) have been demonstrated to be efficient for membrane permeabilization and irreversible electroporation. Since membrane permeabilization has been achieved using HF-BP pulses we hypothesized that with these pulses we can also achieve successful gene electrotransfer (GET). Three variations of bursts of 2 µs bipolar pulses with 2 µs interphase delay were applied in HF-BP protocols. We compared transfection efficiency of monopolar micro and millisecond pulses and HF-BP protocols at various plasmid DNA (pDNA) concentrations on CHO – K1 cells. GET efficiency increased with increasing pDNA concentration. Overall GET obtained by HF-BP pulse protocols was comparable to overall GET obtained by longer monopolar pulse protocols. Our results, however, suggest that although we were able to achieve similar percent of transfected cells, the number of pDNA copies that were successfully transferred into cells seemed to be higher when longer monopolar pulses were used. Interestingly, we did not observe any direct correlation between fluorescence intensity of pDNA aggregates formed on cell membrane and transfection efficiency. The results of our study confirmed that we can achieve successful GET with bipolar microsecond i. e. HF-BP pulses, although at the expense of higher pDNA concentrations.

Fast inactivation of Nav current in rat adrenal chromaffin cells involves two independent inactivation pathways.

Voltage-dependent sodium (Nav) current in adrenal chromaffin cells (CCs) is rapidly inactivating and tetrodotoxin (TTX)-sensitive. The fractional availability of CC Nav current has been implicated in regulation of action potential (AP) frequency and the occurrence of slow-wave burst firing. Here, through recordings of Nav current in rat CCs, primarily in adrenal medullary slices, we describe unique inactivation properties of CC Nav inactivation that help define AP firing rates in CCs. The key feature of CC Nav current is that recovery from inactivation, even following brief (5 ms) inactivation steps, exhibits two exponential components of similar amplitude. Various paired pulse protocols show that entry into the fast and slower recovery processes result from largely independent competing inactivation pathways, each of which occurs with similar onset times at depolarizing potentials. Over voltages from -120 to -80 mV, faster recovery varies from ∼3 to 30 ms, while slower recovery varies from ∼50 to 400 ms. With strong depolarization (above -10 mV), the relative entry into slow or fast recovery pathways is similar and independent of voltage. Trains of short depolarizations favor recovery from fast recovery pathways and result in cumulative increases in the slow recovery fraction. Dual-pathway fast inactivation, by promoting use-dependent accumulation in slow recovery pathways, dynamically regulates Nav availability. Consistent with this finding, repetitive AP clamp waveforms at 1-10 Hz frequencies reduce Nav availability 80-90%, depending on holding potential. These results indicate that there are two distinct pathways of fast inactivation, one leading to conventional fast recovery and the other to slower recovery, which together are well-suited to mediate use-dependent changes in Nav availability.

Behavioral profiling reveals an enhancement of dentate gyrus paired pulse inhibition in a rat model of PTSD

We recently introduced behavioral profiling as a translational approach to increase the validity of animal models of posttraumatic stress disorder (PTSD). Behavioral profiling utilizes the response of a ‘normal population’ of control animals and compares the performance of animals with a history of traumatic stress in different behavioral tests that can capture PTSD-like symptoms. Thus, affected, PTSD-like individuals can be subdivided from resilient trauma-exposed animals.While in our recent study we focused mainly on tests for activity and anxiety, we now expand the behavioral tests battery and include also fear memory and extinction tasks as well as a spatial object recognition test in our behavioral profiling approach. Utilizing underwater trauma as the traumatic event, we found that only a small subset of animals exposed to underwater trauma showed lasting increases in anxiety-like behavior and heightened emotional memory formation. Adding juvenile stress as a model for childhood adversity increased the prevalence of such affected animals and furthermore and induced additional cognitive deficits in a subgroup of such emotionally affected individuals. In addition, multiple affected individual rats displayed increased local circuit activity in the dorsal dentate gyrus, as measured in vivo with paired pulse protocols in anesthetized animals.Together, our findings highlight behavioral profiling, refined by including multiple behavioral tests, as a valid tool to identify PTSD-like vs. resilient individual animals and further suggest that enhanced local inhibition in specific circuits of the dorsal dentate gyrus may be associated with the observed symptoms.

Microsecond Pulsed Electric Fields: An Effective Way to Selectively Target and Radiosensitize Medulloblastoma Cancer Stem Cells

Cancer stem cells constitute an endless reserve for the maintenance and progression of tumors, and they could be the reason for conventional therapy failure. New therapeutic strategies are necessary to specifically target them. In this context, microsecond pulsed electric fields have been selected to expose D283Med cells, a human medulloblastoma cell line resulted to be rich in cancer stem cells, and normal human astrocytes. We analyzed invitro different endpoints at different times after microsecond pulsed electric field exposure, such as permeabilization, reactive oxygen species generation, cell viability/proliferation, cell cycle, and clonogenicity, as well as the expression of different genes involved in cell cycle, apoptosis, and senescence. Furthermore, the response of D283Med cells exposed to microsecond pulsed electric fields was validated invivo in a heterotopic mouse xenograft model. Our invitro results showed that a specific pulse protocol (ie, 0.3 MV/m, 40 μs, 5 pulses) was able to induce irreversible membrane permeabilization and apoptosis exclusively in medulloblastoma cancer stem cells. In the surviving cells, reactive oxygen species generation was observed, together with a transitory G2/M cell-cycle arrest with a senescence-associated phenotype via the upregulation of GADD45A. Invivo results, after pulsed electric field exposure, demonstrated a significant tumor volume reduction with no eradication of tumor mass. In conjunction, we verified the efficacy of electric pulse pre-exposure followed by ionizing irradiation invivo to enable complete inhibition of tumor growth. Our data reveal novel therapeutic options for the targeting of medulloblastoma cancer stem cells, indicating nonionizing pulsed electric field pre-exposure as an effective means to overcome the radioresistance of cancer stem cells.

An in vivo study of a custom-made high-frequency irreversible electroporation generator on different tissues for clinically relevant ablation zones

Purpose To examine the ablation zone, muscle contractions, and temperature increases in both rabbit liver and kidney models in vivo for a custom-made high-frequency irreversible electroporation (H-FIRE) generator. Materials and Methods A total of 18 New Zealand white rabbits were used to investigate five H-FIRE protocols (n = 3 for each protocol) and an IRE protocol (n = 3) for the performance of the designed H-FIRE device in both liver and kidney tissues. The ablation zone was determined by using histological analysis 72 h after treatment. The extent of muscle contractions and temperature change during the application of pulse energy were measured by a commercial accelerometer attached to animals and fiber optic temperature probe inserted into organs with IRE electrodes, respectively. Results All H-FIRE protocols were able to generate visible ablation zones without muscle contractions, for both liver and kidney tissues. The area of ablation zone generated in H-FIRE pulse protocols (e.g., 0.3–1 μs, 2000 V, and 90–195 bursts) appears similar to that of IRE protocol (100 μs, 1000 V, and 90 pulses) in both liver and kidney tissues. No significant temperature increase was noticed except for the protocol with the highest pulse energy (e.g., 1 μs, 2000 V, and 180 bursts). Conclusion Our work serves to complement the current H-FIRE pulse waveforms, which can be optimized to significantly improve the quality of ablation zone in terms of precision for liver and kidney tumors in clinical setting.

Dynamical transition for a class of integrable models coupled to a bath

We study the dynamics of correlation functions of a class of $d-$dimensional integrable models coupled linearly to a fermionic or bosonic bath in the presence of a periodic drive with a square pulse protocol. It is well known that in the absence of the bath, these models exhibit a dynamical phase transition; all correlators decay to their steady state values as $n_0^{-(d+1)/2}$[$n_0^{-d/2}]$ above [below] a critical frequency $\omega_c$, where $n_0$ is the number of drive cycles. We find that the presence of a linearly coupled fermionic bath which maintains integrability of the system preserves this transition. We provide a semi-analytic expression for the evolution operator for this system and use it to provide a phase diagram showing the different dynamical regimes as a function of the system-bath coupling strength and the bath parameters. In contrast, when such models are coupled to a bosonic bath which breaks integrability of the model, we find exponential decay of the correlators to their steady state. Our numerical analysis shows that this exponential decay sets in above a critical number of drive cycles $n_c$ which depends on the system-bath coupling strength and the amplitude of perturbation. Below $n_c$, the system retains the power-law behavior identical to that for the closed integrable models and the dynamical transition survives. We discuss the applicability of our results for interacting fermion systems and discuss experiments which can test our theory.

Intense Pulsed Light as a Treatment for Senile Purpura: A Pilot Study.

Senile purpura is a common condition characterized by recurrent ecchymoses in the elderly on the extensor surfaces of the forearms, hands, and legs. Our objective is to assess the efficacy and safety of a protocol using intense pulsed light (BBL; Sciton Inc., Palo Alto, CA) to improve the appearance of senile purpura on subjects' extensor forearms. Five subjects over 65 years of age, with ecchymotic lesions measuring over 1 cm on each forearm and five younger subjects under 35 years of age, without any ecchymotic lesions, were included in the study. The subjects were treated on one randomized forearm with a new intense pulsed light protocol for four weekly sessions. Photographs and subject questionnaires were taken weekly before each treatment as well as 1 month after all treatments. Skin biopsies were taken 1 day after the last of four weekly treatments. Histological analysis, including hematoxylin and eosin, elastic van Gieson, and Masson's Trichrome staining, were carried out to assess both the epidermal thickness and dermal connective tissue structure. The protocol consists of multiple passes using an intense pulsed light (BBL; Sciton Inc.) device in which the wavelength, filter, and fluence are adjusted for each step. Step 1 uses infrared light (800-1,400 nm), high intensity, a smooth adapter, and a constant motion technique. Step 2 employs a 590-nm filter with two different fluences and step 3 utilizes a 560-nm filter. The fluence of steps 2-3 is increased by 1 J each treatment if no side effects are noted. Using a new intense pulsed light protocol in subjects with senile purpura, both the number and square area of ecchymoses on the treated arm were significantly reduced (P = 0.02 and P = 0.04, respectively, paired t test) as compared with the untreated arm at 1 month after four weekly treatments. Despite this pilot study including challenging cases of subjects on both inhaled and injected corticosteroids and blood thinners, all subjects with senile purpura had at least a 50% reduction in the total square area of their ecchymoses on their treated arm. There were no significant or long-lasting side effects, and all subjects reported satisfaction with the treatment with a desire to continue treatments on their control arm. Blinded evaluators were able to select 100% of the time in the subjects with senile purpura, which was the treated arm as compared with the control arm when reviewing photographs from 1 month after the last treatment. In addition, several subjects were noted to have a significant improvement in the appearance of hemosiderin deposition and photodamage. Histologically, intense pulsed light treatments significantly increased epidermal thickness in elderly subjects by 21.14% (P = 0.0153, two-tailed, paired t test), to levels comparable with young subjects. Such restoration is consistent with the other histological observations by blinded evaluators of more abundant and organized collagen fibers in the dermis and reduced aggregates of disorganized elastin fibers. This new intense pulsed light protocol is safe and effective in improving the clinical appearance of senile purpura as well as preventing future lesions by improving the structure of the skin by increasing epidermal thickness and improving collagen and elastic fiber morphology. The treatment was well-tolerated, adverse effects were minimal, and there was high patient satisfaction. Lasers Surg. Med. 2020. © 2020 Wiley Periodicals LLC.

Contrasting alterations between cortical and subcortical myelin across age, AD diagnosis, and amyloid and tau pathology as assessed by quantitative R1 mapping

AbstractBackgroundAccumulation of pathology in cortical tissue are early pathological hallmarks of Alzheimer’s disease. High resolution T1w/T2w ratio maps from structural MRI may reflect tissue microstructure with sensitivity to myelin, iron, and dendritic density. Few studies have investigated this in AD with conflicting reports of directionality of T1w/T2w ratios in individuals with AD diagnosis and pathology. However, these ratios will be sensitive to pulse sequences, protocols and bias field inhomogeneities, limiting their utility in clinical and research contexts. Here we employ R1 (=1/T1) relaxometry mapping, a quantitative imaging measure that is sensitive to myelin, to investigate relationships between cortical and subcortical tissue microstructure, age, AD diagnosis, and amyloid and tau pathology.MethodParticipants from the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention underwent 3T MRI with whole‐brain, 1mm isotropic MPnRAGE T1 relaxometry with motion correction (Kecskemeti et al., 2016) (N=605/CN, 39/AD; age = 65.49 +/‐ 7.89 yrs) with a subset undergoing lumbar puncture for CSF Aß42/Tau biomarker classification (N = 141/A‐T‐, 26/A+T‐, 22/A‐T+, 18/A+T+). T1‐weighted images were processed using ANTS and CAT12, and transformation warps were applied to produce subcortical R1 maps in MNI space (6mm smoothing) and cortical R1 surface meshes (164k mesh, 5mm smoothing). Vertex‐wise (GM) and voxel‐wise (WM) ANCOVA were performed (p<0.05 FWE corrected). Covariates included age, sex, study protocol, and AD diagnosis in model 1, and age, sex, years between CSF collection and MRI, study protocol, and A/T biomarker group in model 2.ResultSignificant associations between R1 and age, clinical AD diagnosis, and A/T pathology were found (Figure 1A‐C). Post‐hoc tests revealed increased R1 due to A/T pathology driven by A+T+ individuals. In contrast, significant widespread decreases in subcortical R1 were found with age and AD diagnosis (Figure 1D&E), with no significant alterations in subcortical R1 due to biomarker status.ConclusionCortical and subcortical tissue exhibit differential tissue microstructural changes in response to aging, AD diagnosis and pathology. Importantly, increases in cortical R1 in unimpaired A+T+ individuals may reflect increased remyelination prior to the development of cognitive impairment. Future research will assess longitudinal relationships of R1 with age, cognition and markers of neurodegeneration.

Heating of Hip Arthroplasty Implants During Metal Artifact Reduction MRI at 1.5- and 3.0-T Field Strengths.

The aim of this study was to quantify the spatial temperature rises that occur during 1.5- and 3.0-T magnetic resonance imaging (MRI) of different types of hip arthroplasty implants using different metal artifact reduction techniques. Using a prospective in vitro study design, we evaluated the spatial temperature rises of 4 different total hip arthroplasty constructs using clinical metal artifact reduction techniques including high-bandwidth turbo spin echo (HBW-TSE), slice encoding for metal artifact correction (SEMAC), and compressed sensing SEMAC at 1.5 and 3.0 T. Each MRI protocol included 6 pulse sequences, with imaging planes, parameters, and coverage identical to those in patients. Implants were immersed in standard American Society for Testing and Materials phantoms, and fiber optic sensors were used for temperature measurement. Effects of field strength, radiofrequency pulse polarization at 3.0 T, pulse protocol, and gradient coil switching on heating were assessed using nonparametric Friedman and Wilcoxon signed-rank tests. Across all implant constructs and MRI protocols, the maximum heating at any single point reached 13.1°C at 1.5 T and 1.9°C at 3.0 T. The temperature rises at 3.0 T were similar to that of background in the absence of implants (P = 1). Higher temperature rises occurred at 1.5 T compared with 3.0 T (P < 0.0001), and circular compared with elliptical radiofrequency pulse polarization (P < 0.0001). Compressed sensing SEMAC generated equal or lower degrees of heating compared with HBW-TSE at both field strengths (P < 0.0001). Magnetic resonance imaging of commonly used total hip arthroplasty implants is associated with variable degrees of periprosthetic tissue heating. In the absence of any perfusion effects, the maximum temperature rises fall within the physiological range at 3.0 T and within the supraphysiologic range at 1.5 T. However, with the simulation of tissue perfusion effects, the heating at 1.5 T also reduces to the upper physiologic range. Compressed sensing SEMAC metal artifact reduction MRI is not associated with higher degrees of heating than the HBW-TSE technique.

Evaluation of pulsed electromagnetic field protocols in implant osseointegration: in vivo and in vitro study.

The present study aims to evaluate two protocols of pulsed electromagnetic field (PEMF) on osseointegration and establish one that addresses ideal parameters for its use in dentistry, especially in the optimization of the implants osseointegration process. Sixty male rats (Wistar) were allocated into three experimental groups: control (GC), test A (GTA, 3h exposed), and test B (GTB, 1h exposed). All animals received titanium implants in both tibias, and PEMF application (15Hz, ± 1mT, 5days/week) occurred only in the test groups. They were euthanized at 03, 07, 21, and 45days after PEMF therapy. Removal torque, histomorphometric measurements, three-dimensional radiographic evaluation, and in vitro biological assay analyses were performed. GTB showed better results compared with GTA in removal torque tests, in bone volume and bone mineral density, cell viability, total protein content, and mineralization nodules (p < 0.05). GTA showed better performance in trabecular bone thickness and cell proliferation compared with GTB (p < 0.05), especially at osseointegration early periods. In the histomorphometric analysis and number of trabeculae, there were no differences in the test groups. PEMF as a biostimulator was effective in optimizing the events in bone tissue that lead to osseointegration, especially when applied for a shorter time and in the initial periods of bone healing. The PEMF therapy is an effective alternative method for optimizing bone healing.

Therapeutic effects of ultrasound on dermal wound healing in diabetic mice

Some evidence indicates that relatively low intensity, pulsed ultrasound can enhance soft tissue regeneration in both animal models and humans. However, the effectiveness of therapeutic ultrasound can vary among populations. Here, we investigated effects of ultrasound on dermal wound healing using a murine model of chronic, diabetic wounds. Full thickness, punch biopsy wounds were made on the dorsal skin of genetically diabetic, male mice. Wounds were exposed to 1-MHz pulsed ultrasound (2 ms pulse, 100Hz PRF, 0–0.4 MPa) for 8 min per day, for either 2 or 3 weeks. After 2 weeks, the average granulation tissue thickness at the center of wounds exposed to 0.4 MPa ultrasound was significantly increased compared to sham-exposed wounds. Interestingly, the mean granulation tissue thickness of one subpopulation of mice exposed to 0.4 MPa was significantly greater than that of a second subpopulation (594 ± 41 μm, n = 9 vs 62 ± 25 μm, n = 10). Increasing the treatment time to 3 weeks increased the percentage of mice with fully re-epithelialized wounds from 47% at 2-weeks to 86%, and significantly reduced wound diameter. These data demonstrate a dose-dependent difference in the responsiveness of young, male diabetic mice to pulsed ultrasound treatment protocols.

Generalised hyper-Ramsey spectroscopy of two-level atoms in an optically dense medium

The peculiarities of Ramsey resonance and its sensitivity to the light shift from an optically dense medium of cold atoms are investigated. Different composite pulse protocols for clock spectroscopy, including hyper-Ramsey, modified and generalised hyper-Ramsey schemes, are compared. Error signals change significantly due to the processes of absorption and dispersion in the atomic medium. The dependence of the position of the central fringe resonance with a residual uncompensated light shift of the atomic transition is studied with the attenuation of the radiation intensity in the medium taken into account. It is shown that using a combination of generalised hyper-Ramsey error signals allows one to suppress the sensitivity to the light shift for any length of the medium.

Programming-Pulse Dependence of Ferroelectric Partial Polarization: Insights From a Comparative Study of PZT and HZO Capacitors

The programming of partial polarization in ferroelectric (FE) hafnium zirconate (HZO) capacitors is shown to depend on the delay between FE reset and the polarization write pulse (delay-before-write), revealing a subtle history dependence. Programming is substantially independent of delays inserted after the write and before the read (delay-before-read), with no decay in partial polarization observed from $1~\mu \text{s}$ up to 260 ms. We further show that nonsaturation in FE polarization can be introduced if the pulse protocol is not strictly symmetric, where strictly symmetric means that the integral of the voltage waveform over a single measurement cycle is zero. The delay-before-write dependence in HZO is compared with lead-zirconium-titanate (PZT) capacitors used in FE random access memory (FRAM) which shows much weaker dependence. The delay dependence is attributed to the dynamics of subcritical nuclei formation in nucleation limited switching. For the first time, the decay of subcritical nuclei in HZO is shown to be observable up to 1 s, and an upper bound on their volume is estimated to be ~10 nm3, corresponding to $\sim {4}\times {4} \times {4}$ unit cells.

Dynamics of the vacuum state in a periodically driven Rydberg chain

We study the dynamics of the periodically driven Rydberg chain starting from the state with zero Rydberg excitations (vacuum state denoted by $|0\rangle$) using a square pulse protocol in the high drive amplitude limit. We show, using exact diagonalization for finite system sizes ($L\le 26$), that the Floquet Hamiltonian of the system, within a range of drive frequencies which we chart out, hosts a set of quantum scars which have large overlap with the $|0\rangle$ state. These scars are distinct from their counterparts having high overlap with the maximal Rydberg excitation state ($|\mathbb{Z}_2\rangle$); they coexist with the latter class of scars and lead to persistent coherent oscillations of the density-density correlator starting from the $|0\rangle$ state. We also identify special drive frequencies at which the system undergoes perfect dynamic freezing and provide an analytic explanation for this phenomenon. Finally, we demonstrate that for a wide range of drive frequencies, the system reaches a steady state with sub-thermal values of the density-density correlator. The presence of such sub-thermal steady states, which are absent for dynamics starting from the $|\mathbb{Z}_2\rangle$ state, imply a weak violation of the eigenstate thermalization hypothesis in finite sized Rydberg chains distinct from that due to the scar-induced persistent oscillations reported earlier. We conjecture that in the thermodynamic limit such states may exist as pre-thermal steady states that show anomalously slow relaxation. We supplement our numerical results by deriving an analytic expression for the Floquet Hamiltonian using a Floquet perturbation theory in the high amplitude limit which provides an analytic, albeit qualitative, understanding of these phenomena at arbitrary drive frequencies. We discuss experiments which can test our theory.

Pulsed electrodeposition of Ag+ doped prosthetic Fluorohydroxyapatite coatings on stainless steel substrates.

In order to reinforce the antibacterial character of fluorohydroxyapatite (FHA) prosthetic layers on 316L stainless steel (316L SS), Ag+ ions (an antibacterial agent) are included in the electrodeposition medium to be incorporated in the FHA layers created by pulsed protocol. The doped coatings (Ag-FHA) with different concentrations of silver ions (5, 10, 20, 40 and 100ppm) were characterized electrochemically (polarization curves and electrochemical impedance spectroscopy) in simulated body fluid (SBF) solution and microbiologically against two pathogenic bacteria (Staphylococcus aureus and Escherichia coli). XPS, EDX and Raman spectroscopies were used to complement these evaluations. Whatever the concentration of incorporated Ag+ ions, the FHA morphology, structure and composition are not affected. The XPS and EDX results confirm the Ag+ presence within the apatite crystals, mostly concentrated at the extreme surface of the coatings. They also show the lowering of the stoichiometry of the coatings, confirmed by Raman analyses. The corrosion studies indicate that the prosthetic coatings act as a barrier against corrosion of the 316L SS alloy. Moreover, the results of the microbiological tests show that a content of 40ppm of silver, introduced into the prosthetic coatings, inhibits the bacterial growth. Lower concentrations showing only a partial inhibition. In conclusion, using a pulsed current mode in the electrodeposition processes generates Ag-FHA/316L SS systems suitable for biomedical applications.

Restoring coherence via aperiodic drives in a many-body quantum system

We study the unitary dynamics of randomly or quasi-periodically driven tilted Bose-Hubbard (tBH) model in one dimension deep inside its Mott phase starting from a $\mathbb{Z}_2$ symmetry-broken state. The randomness is implemented via a telegraph noise protocol in the drive period while the quasi-periodic drive is chosen to correspond to a Thue-Morse sequence. The periodically driven tBH model (with a square pulse protocol characterized by a time period $T$) is known to exhibit transitions from dynamical regimes with long-time coherent oscillations to those with rapid thermalization. Here we show that starting from a regime where the periodic drive leads to rapid thermalization, a random drive, which consists of a random sequence of square pulses with period $T+\alpha dT$, where $\alpha=\pm 1$ is a random number and $dT$ is the amplitude of the noise, restores long-time coherent oscillations for special values of $dT$. A similar phenomenon can be seen for a quasi-periodic drive following a Thue-Morse sequence where such coherent behavior is shown to occur for a larger number of points in the $(T, dT)$ plane due to the additional structure of the drive protocol. We chart out the dynamics of the system in the presence of such aperiodic drives, provide a qualitative analytical understanding of this phenomenon, point out the role of quantum scars behind it, and discuss experiments which can test our theory.

Influence of pulsed and moderate electric field protocols on the reversible permeabilization and drying of Thai basil leaves

The effect of electroporation parameters on the reversible permeabilization of cells in Thai basil leaves and, specifically, cells on the leaf surface was investigated, as electroporation of stomatal guard cells decreases drying times. Various combinations of PEF and MEF parameters were applied. The effect of these parameters on the electroporation of the leaf surface was assessed with microscopic observations and the electroporation of the bulk tissues was tested with electrical resistance measurements. With PEF and MEF, the electroporation of the epidermal cells increased with increasing treatment time. Compared to epidermal cells, guard cells required larger number of pulses to achieve homogeneous electroporation. Results showed that electroporation of cells on the leaf surface increased with the increase of voltage, pulse width and number of pulses. The electroporation of cells in the bulk tissues increased with increasing voltage and pulse width. Six specific combinations of parameters were found to electroporate the guard cells on the leaf surface while maintaining the viability of the leaves.

Microwave irradiation-based rapid curing of PDMS for microfluidic applications

Microfluidic devices are routinely fabricated using replica moulding. The master relief structure is generally constructed on a silicon substrate and the stamps are made using polydimethylsiloxane (PDMS), cured via the slow process of hot-air convective heating. An alternative method that greatly reduces this cure time is presented here. It employs a low-cost, consumer-grade microwave oven and speeds up the curing process by permitting a much higher heat flux to be applied to the prepolymer. A specific pulsed irradiation protocol has been devised which achieves precisely controlled energy delivery for this purpose. This is necessary because silicon’s relatively much stronger microwave absorption causes uncontrollable temperature overshoots that could degrade PDMS if continuously irradiated. The protocol has been arrived at after due optimization of operational parameters, achieved via simulation of a finite element model. It has been implemented by modifying the control circuitry of the consumer grade oven. Cure times as low as two minutes have been demonstrated. Optical and mechanical characterization results show no adverse effect on the performance of PDMS cured using the proposed method. Thus, it can be used for the rapid fabrication of PDMS-based microfluidic devices and would be especially beneficial for research labs looking to speed up microfluidic device development iterations.

Biophysical defects of an SCN5A V1667I mutation associated with epinephrine-induced marked QT prolongation.

The epinephrine infusion test (EIT) typically induces marked QT prolongation in LQT1, but not LQT3, while the efficacy of β-blocker therapy is established in LQT1, but not LQT3. We encountered an LQT3 family, with an SCN5A V1667I mutation, that exhibited epinephrine-induced marked QT prolongation. Wild-type (WT) or V1667I-SCN5A was transiently expressed into tsA-201 cells, and whole-cell sodium currents (INa ) were recorded using patch-clamp techniques. To mimic the effects of epinephrine, INa was recorded after the application of protein kinase A (PKA) activator, 8-CPT-cAMP (200 μM), for 10 minutes. The peak density of V1667I-INa was significantly larger than WT-INa (WT: 469 ± 48 pA/pF, n = 20; V1667I: 690 ± 62 pA/pF, n = 19, P < .01). The steady-state activation (SSA) and fast inactivation rate of V1667I-INa were comparable to WT-INa . V1667I-INa displayed a significant depolarizing shift in steady-state inactivation (SSI) in comparison to WT-INa (V1/2 -WT: -88.1 ± 0.8 mV, n = 17; V1667I: -82.5 ± 1.1 mV, n = 17, P < .01), which increases window currents. Tetrodotoxin (30 μM)-sensitive persistent V1667I-INa was comparable to WT-INa . However, the ramp pulse protocol (RPP) displayed an increased hump in V1667I-INa in comparison to WT-INa . Although 8-CPT-cAMP shifted SSA to hyperpolarizing potentials in WT-INa and V1667I-INa to the same extent, it shifted SSI to hyperpolarizing potentials much less in V1667I-INa than in WT-INa (V1/2 -WT: -92.7 ± 1.3 mV, n = 6; V1667I: -85.3 ± 1.6 mV, n = 6, P < .01). Concordantly, the RPP displayed an increased hump in V1667I-INa , but not in WT-INa . We demonstrated an increase of V1667I-INa by PKA activation, which may provide a rationale for the efficacy of β-blocker therapy in some cases of LQT3.