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Lafora disease (LD) is a syndrome of progressive myoclonic epilepsy and cumulative neurocognitive deterioration caused by recessively inherited genetic lesions of EPM2A (laforin) or NHLRC1 (malin). Neuropsychiatric symptomatology in LD is thought to be directly downstream of neuronal and astrocytic polyglucosan aggregates, termed Lafora bodies (LBs), which faithfully accumulate in an age‐dependent manner in all mouse models of LD. In this study, we applied home‐cage monitoring to examine the extent of neurobehavioral deterioration in a model of malin‐deficient LD as a means to identify robust preclinical endpoints that may guide the selection of novel genetic treatments. At 6 weeks, ∼6–7 months, and ∼12 months of age, malin‐deficient mice ("KO") and wild‐type (WT) littermates underwent a standardized home‐cage behavioral assessment designed to non‐obtrusively appraise features of rest/arousal, consumptive behaviors, risk aversion, and voluntary wheel‐running. At all timepoints, and over a range of metrics that we report transparently, WT and KO mice were essentially indistinguishable. In contrast, within WT mice compared across the same timepoints, we identified age‐related nocturnal hypoactivity, diminished sucrose preference, and reduced wheel‐running. Neuropathological examinations in subsets of the same mice revealed expected age‐dependent LB accumulation, gliosis, and microglial activation in cortical and subcortical brain regions. At 12 months of age, despite the burden of neocortical LBs, we did not identify spontaneous seizures during an electroencephalographic (EEG) survey, and KO and WT mice exhibited similar spectral EEG features. However, in an in vitro assay of neocortical function, paroxysmal bursts of network activity (UP states) in KO slices were more prolonged at 3 and 6 months of age, but similar to WT at 12 months. KO mice displayed a distinct response to pentylenetetrazole, with a greater incidence of clonic seizures and a more pronounced postictal suppression of movement, feeding, and drinking behavior. Together, these results highlight the clinicopathologic dissociation in a mouse model of LD, where the accrual of LBs may latently modify cortical circuit function and seizure threshold without clinically meaningful changes in home‐cage behavior. Our findings allude to a delay between LB accumulation and neurobehavioral decline in LD: one that may provide a window for treatment, and whose precise duration may be difficult to ascertain within the typical lifespan of a laboratory mouse. [ABSTRACT FROM AUTHOR]

Crocin is a pharmacologically active carotenoid pigment mainly present in the stigmas of Crocus sativus L. (Iridaceae). It has been well explored in experimental animal models of cognitive impairments, depression, anxiety and epilepsy. This study was designed to understand the effect of crocin on pentylenetetrazol (PTZ)-induced kindling development and its associated cognitive deficit in mouse. Crocin treatment at 5, 10 and 20 mg/kg p.o. doses showed a marked reduction in severity of PTZ-induced seizures. There was an increase in novel object preference index and discrimination ratio in the crocin-treated groups in the novel object recognition test. Its treatment also increased percentage spontaneous alternations in T-maze test at all the tested doses. Histopathological examination by Nissl staining showed a reduction in dark neurons in the hippocampal pyramidal layer of crocin-treated animals in contrast to vehicle control, indicating a decrease in neuronal damage. Biochemical estimations showed a significant increase in superoxide dismutase activity and reduced reactive oxygen species (ROS) in the hippocampus of crocin-treated animals. Immunohistochemistry results revealed attenuation in the levels of nuclear factor-κB (NF-κB) and phosphorylated NF-κB in the hippocampal sections of crocin-treated animals. The results of this study concluded that crocin treatment increased seizure threshold, thus inhibiting PTZ-induced kindling development and improving cognitive functions. The effect was found to be due to suppression of seizure-induced ROS generation and its linked NF-κB pathway-associated neuronal damage. [ABSTRACT FROM AUTHOR]

A dynamic voltage restorer (DVR) is a power-electronic controller that can protect sensitive loads from disturbances in the supply system. In this paper, it is demonstrated that this device can tightly regulate the voltage at the load terminal against imbalance or harmonic in the source side. The behavior of the device is studied through steady-state analysis, and limits to achievable performance are found. This analysis is extended to the study of transient operation where the generation of the reference voltage of the DVR is discussed. Once the reference signals are generated, they are tracked using a switching band scheme. A suitable structure in which the DVR is realized by voltage-source inverters (VSIs) is also discussed. Particular emphasis to the rating of this device is provided. Extensive simulation results are included to illustrate the operating principles of a DVR. [ABSTRACT FROM AUTHOR]

Graphene constitutes one of the key elements in many functional van der Waals heterostructures. However, it has negligible optical visibility due to its monolayer nature. Here we study the visibility of graphene in various van der Waals heterostructures and include the effects of the source spectrum, oblique incidence and the spectral sensitivity of the detector to obtain a realistic model. A visibility experiment is performed at different wavelengths, resulting in a very good agreement with our calculations. This allows us to reliably predict the conditions for better visibility of graphene in van der Waals heterostructures. The framework and the codes provided in this work can be extended to study the visibility of any 2D material within an arbitrary van der Waals heterostructure. [ABSTRACT FROM AUTHOR]

The propagation of a weak probe field through a four-level inverted-Y type atomic system driven by two additional coherent fields, namely the control field and the repump field, is studied. The simulated probe absorption shows that electromagnetically induced transparency and the line shape of the transparency window under a Doppler-broadened condition are dependent on the residual Doppler averaging due to the wavelength mismatch between the control and probe fields. For 87Rb the probe propagation changes from subluminal on-resonance under a Doppler-free condition to superluminal on-resonance under a Doppler-broadened condition. For both 87Rb and 133Cs, the narrow subluminal window occurring in the group index profile in a Doppler-free environment offers an excellent delay bandwidth for probe field propagation. Under this condition, the order of the delay in probe field propagation can be as long as a few hundred µs and seems quite promising in the field of optical delay generation and light storage. The analysis shows that the residual Doppler averaging has a greater impact on the switching window under the variation of the Rabi frequency of the control field as compared to that of the repump field. [ABSTRACT FROM AUTHOR]

Pyrrolone-fused benzosuberene (PBS) compounds were semi-synthesized from α,β,γ-Himachalenes extracted from the essential oil of Cedrus deodara following amino-vinyl-bromide substituted benzosuberenes as intermediates. These PBSs compounds classified as an attractive source of therapeutics. The α-isoform of PI3K which is a pivotal modulator of PI3K/AKT/mTOR signaling pathway, responsible for neurological disorders like epilepsy, found as a potential target molecule against these 17 semi-synthesized PBS compounds using in silico ligand-based pharmacophore mapping and target screening. The compounds screened using binding affinities, ADMET properties, and toxicity that were accessed by in silico docking simulations and pharmacokinetics profiling. Ultimately two compounds viz., PBS-8 and PBS-9 were selected for further in vivo evaluation using a zebrafish (Danio rerio) model of pentylenetetrazol (PTZ)-induced clonic convulsions. Additionally, gene expression studies performed for the genes of the PI3K/AKT/mTOR pathway which further validated our results. In conclusion, these findings suggested that PBS-8 is a promising candidate that could bedeveloped as a potential antiepileptic. [ABSTRACT FROM AUTHOR]

Effect of residual Doppler averaging on the probe absorption in an alkali vapor medium in the presence of a coherent pump beam is studied analytically for the Ξ type system. A coherent probe field is assumed to connect the ground level with the intermediate level whereas a coherent control beam is supposed to act between the intermediate energy level and the uppermost level. Optical Bloch equations (OBE) for a three-level Ξ type system and a four-level Ξ type system are derived by using density matrix formalism. These equations are solved by an analytic method to determine the probe response, which not only depends on the wavelength difference between the control (pump) field and the probe field but shows substantially different features depending on whether the wavelength of the control field is greater than that of the probe field or the reverse. The effect of temperature on probe response is also shown. Enhancement in probe absorption and additional features are noticed under a strong probe limit at room temperature. The four-level Ξ type system has two ground levels and this leads to substantial modification in the simulated probe absorption as compared to the three-level system. [ABSTRACT FROM AUTHOR]

Coherent probe field (LA) propagation through an eight-level inverted Y-type atomic system, in the presence of two additional coherent radiation fields termed the field LC (control or pump field) and the field LB (repump field), is investigated by using the parameters of 87Rb transitions. The system has two ground energy levels, four intermediate energy levels, and two uppermost energy levels. A theoretical model based on the density matrix method is used for numerical simulation of the probe response under different conditions. Simulated probe absorption spectra under a Doppler-free condition as well as under thermal averaging exhibit electromagnetically induced transparency (EIT). The position and line shape of this EIT profile change with different detunings of the control and repump fields. When the three coherent fields share a common level, a funnel-like EIT window appears in the simulated probe absorption curve. Velocity selective optically pumped absorption peaks are seen in the simulated probe response at room temperature. [ABSTRACT FROM AUTHOR]

The absorption features of a probe field propagating through a four-level N-type atomic system in the presence of two coherent radiation fields is studied analytically by using a density matrix formulation. The system has two ground levels and two excited levels. A weak probe laser couples the upper ground level to the lower excited level whereas a strong control field connects the lower ground level to the lower excited level. The coupling field acts between the upper ground level and the upper excited level. The transition parameters of the 87Rb D1 line have been used to simulate the probe response. The simulated probe absorption shows a gain-like structure depending on the relative field intensities. The spectral features of the probe response exhibit substantial differences under thermal averaging as compared to a Doppler-free condition. The splitting of simulated probe absorption can be explained by the dressed state model. Electromagnetically induced absorption (EIA) is observed in the simulated probe response curve when the spontaneous decay of the population from the uppermost excited state to the lower ground state is absent. [ABSTRACT FROM AUTHOR]

We report the occurrence of electromagnetically induced transparency (EIT) in the simulated probe response signal for a four-level inverted-Y type system that is being acted upon by a weak coherent probe field, a strong coherent pump field and a coherent repump field. There are two ground energy levels, one intermediate energy level and one uppermost energy level. The weak probe field couples the lowest ground level to the intermediate level whereas the repump field connects the other ground level with the intermediate level. The strong control field couples the intermediate level with the uppermost energy level, thereby forming an inverted-Y type system. The density matrix based theoretical model has been developed and solved analytically for this four-level system and the probe response signal has been simulated at different values of the control and repump Rabi frequencies, control and repump frequency detunings and under both Doppler-free and Doppler-broadened conditions using the parameters of 87Rb D2 transition. Extremely low line width (few tens of kHz) for the EIT signal has been noticed under thermal averaging for copropagating probe, control and repump field configuration. The EIT signal is found to be immune to the variation in the control Rabi frequency. [ABSTRACT FROM AUTHOR]

We have addressed the microscopic transport mechanism at the switching or ‘on–off’ transition in transition metal dichalcogenide (TMDC) field-effect transistors (FETs), which has been a controversial topic in TMDC electronics, especially at room temperature. With simultaneous measurement of channel conductivity and its slow time-dependent fluctuation (or noise) in ultrathin WSe2 and MoS2 FETs on insulating SiO2 substrates where noise arises from McWhorter-type carrier number fluctuations, we establish that the switching in conventional backgated TMDC FETs is a classical percolation transition in a medium of inhomogeneous carrier density distribution. From the experimentally observed exponents in the scaling of noise magnitude with conductivity, we observe unambiguous signatures of percolation in a random resistor network, particularly, in WSe2 FETs close to switching, which crosses over to continuum percolation at a higher doping level. We demonstrate a powerful experimental probe to the microscopic nature of near-threshold electrical transport in TMDC FETs, irrespective of the material detail, device geometry, or carrier mobility, which can be extended to other classes of 2D material-based devices as well. [ABSTRACT FROM AUTHOR]

We report the observation of electromagnetically induced transparency (EIT) in a six-level Λ-type system in atomic Rb vapor containing both 87Rb and 85Rb. The experimental observation includes five velocity selective optically pumped (VSOP) absorption dips for both 87Rb and 85Rb. The EIT signal appears on the background of one such VSOP absorption dips. The measured EIT linewidth () shows sub-natural ( ) values for both lower and higher values of pump Rabi-frequencies. The density matrix based theoretical model for the six-level system is developed and solved numerically by taking into account the Doppler broadening. A complete analytical solution (non perturbative) for a three level Λ-type system has been obtained and compared with the experimentally observed sub-natural EIT linewidth. The simulated spectra are in good agreement with the experimental findings. [ABSTRACT FROM AUTHOR]