Effect of Buffer Layer Capacitance on the Electrical Characteristics of Ferroelectric Polymer Capacitors and Field Effect Transistors.

We demonstrated the effect of a buffer layer on the electrical characteristics of ferroelectric polymer capacitors and field-effect transistors. Various polymer materials with a dielectric constant between 2 and 42 were used to form buffer layers with a similar thicknesses, but with different capacitances. In order to evaluate the characteristics of the ferroelectrics with a buffer layer, the polarization-voltage characteristics of the capacitor, the transfer characteristics, and the retention characteristics of the transistors were investigated. As the capacitance of the buffer layer increased, high remnant polarization (Pr), high hysteresis, and long retention times were observed. Exceptionally, when poly(methylmethacrylate) and rigid poly(aryl ether) (poly(9,9-bis(4-hydroxyphenyl)fluorene-co-decafluorobiphenyl)) were used as the buffer layer, Pr had a value close to 0 in the dynamic measurement polarization-voltage (P-V) characteristic, but the quasi-static measurement transfer characteristic and the static measurement retention characteristic showed relatively high hysteresis and long retention times. Our study provides a scientific and technical basis for the design of ferroelectric memory and neuromorphic devices.

Combination Laser Treatment With Real-Time Ultrasound Navigation for Oral Venous Malformations.

Vascular lesions, including hemangiomas and vascular malformations, are common benign diseases. More than 50% originate from blood vessels or vascular structures and are locate in the head and neck region. This study aimed to evaluate the efficiency and safety of a combination of laser treatments for oral venous malformations using ultrasound navigation. This study reports 3 cases of massive vascular malformation in the oral cavity, which were treated by a combination of a multiple spotted transmucosal irradiation technique (the so-called leopard technique) for the superficial layer, and intralesional photocoagulation for the deep layer using a neodymium-doped yttrium aluminum garnet laser, under real-time ultrasound navigation. All cases presented with a venous malformation with multiple blue swellings on the dorsum of the tongue, which had a maximum dimension of over 30 mm. The percent reduction in the size of the lesions was determined by magnetic resonance imaging. All cases showed a decrease in lesion volume of over 80%, without extensive tissue necrosis, 6 to 12 months after the laser treatment. None of the patients experienced any complications, and all were satisfied with the treatment outcome after one irradiation session.The results of this study suggest that laser treatment using ultrasound navigation is a promising approach for the safe and minimally invasive resolution of oral vascular lesions without scarring and loss of normal tissue architecture, sensation, oral function.

Effect of gambierol and its tetracyclic and heptacyclic analogues in cultured cerebellar neurons: a structure-activity relationships study.

The polycyclic ether class of marine natural products has attracted the attention of researchers due to their complex and large chemical structures and diverse biological activities. Gambierol is a marine polycyclic ether toxin, first isolated along with ciguatoxin congeners from the dinoflagellate Gambierdiscus toxicus. The parent compound gambierol and the analogues evaluated in this work share the main crucial elements for biological activity, previously described to be the C28=C29 double bond within the H ring and the unsaturated side chain [Fuwa, H., Kainuma, N., Tachibana, K., Tsukano, C., Satake, M., and Sasaki, M. (2004) Diverted total synthesis and biological evaluation of gambierol analogues: Elucidation of crucial structural elements for potent toxicity. Chem. Eur. J. 10, 4894-4909]. With the aim to gain a deeper understanding of the cellular mechanisms involved in the biological activity of these compounds, we compared its activity in primary cultured neurons. The three compounds inhibited voltage-gated potassium channels (Kv) in a concentration-dependent manner and with similar potency, caused a small inhibition of voltage-gated sodium channels (Nav), and evoked cytosolic calcium oscillations. Moreover, the three compounds elicited a "loss of function" effect on Kv channels at concentrations of 0.1 nM. Additionally, both the tetracyclic and the heptacyclic derivatives of gambierol elicited synchronous calcium oscillations similar to those previously described for gambierol in cultured cerebellar neurons. Neither gambierol nor its tetracyclic derivative elicited cell toxicity, while the heptacyclic analogue caused a time-dependent decrease in cell viability. Neither the tetracyclic nor the heptacyclic analogues of gambierol exhibited lethality in mice after ip injection of 50 or 80 µg/kg of each compound. Altogether, the results presented in this work support an identical mechanism of action for gambierol and its tetracyclic and heptacyclic analogues and indicate a "loss of function" effect on potassium channels even after administration of the three compounds at subnanomolar concentrations. In addition, because gambierol is known to stabilize the closed state of Kv3 channels, the results presented in this paper may have implications for understanding of channel functions and for future development of therapies against ciguatera poisoning and potassium channel-related diseases.

Design and synthesis of skeletal analogues of gambierol: attenuation of amyloid-ß and tau pathology with voltage-gated potassium channel and N-methyl-D-aspartate receptor implications.

Gambierol is a potent neurotoxin that belongs to the family of marine polycyclic ether natural products and primarily targets voltage-gated potassium channels (K(v) channels) in excitable membranes. Previous work in the chemistry of marine polycyclic ethers has suggested the critical importance of the full length of polycyclic ether skeleton for potent biological activity. Although we have previously investigated structure-activity relationships (SARs) of the peripheral functionalities of gambierol, it remained unclear whether the whole polycyclic ether skeleton is needed for its cellular activity. In this work, we designed and synthesized two truncated skeletal analogues of gambierol comprising the EFGH- and BCDEFGH-rings of the parent compound, both of which surprisingly showed similar potency to gambierol on voltage-gated potassium channels (K(v)) inhibition. Moreover, we examined the effect of these compounds in an in vitro model of Alzheimer's disease (AD) obtained from triple transgenic (3xTg-AD) mice, which expresses amyloid beta (Aß) accumulation and tau hyperphosphorylation. In vitro preincubation of the cells with the compounds resulted in significant inhibition of K(+) currents, a reduction in the extra- and intracellular levels of Aß, and a decrease in the levels of hyperphosphorylated tau. In addition, pretreatment with these compounds reduced the steady-state level of the N-methyl-D-aspartate (NMDA) receptor subunit 2A without affecting the 2B subunit. The involvement of glutamate receptors was further suggested by the blockage of the effect of gambierol on tau hyperphosphorylation by glutamate receptor antagonists. The present study constitutes the first discovery of skeletally simplified, designed polycyclic ethers with potent cellular activity and demonstrates the utility of gambierol and its synthetic analogues as chemical probes for understanding the function of K(v) channels as well as the molecular mechanism of Aß metabolism modulated by NMDA receptors.

Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretase inhibitors.

Divergent synthesis of multifunctional molecular probes based on caprolactam-derived dipeptidic gamma-secretase inhibitors (GSIs), Compound E (CE) and LY411575 analogue (DBZ), was efficiently accomplished by means of Cu(I)-catalyzed azide/alkyne fusion reaction. Photoaffinity labeling experiments using these derivatives coupled to photoactivatable and biotin moieties provided direct evidence that the molecular targets of CE and DBZ are the N-terminal fragment of presenilin 1 within the gamma-secretase complex. Moreover, these photoprobes directly targeted signal peptide peptidase. These data suggest that the divergent synthesis of molecular probes has been successfully applied to characterize the interaction of GSIs with their molecular targets and define the structural requirements for inhibitor binding to intramembrane-cleaving proteases.