Enhanced growth inhibition of hepatic multicellular tumor spheroids by lactosylated poly(ethylene glycol)-siRNA conjugate formulated in PEGylated polyplexes

PEGylated polyplexes (lac-PEGylated polyplexes) composed of poly(L-lysine) and lactosylated poly(ethylene glycol)-small interfering RNA conjugate, which inhibits the RecQL1 gene product, were revealed to show an appreciable growth inhibition of multicellular HuH-7 spheroids (human hepatocarcinoma cell lines) for up to 21 days (IC(50)=6 nM); this system used as an in vitro three-dimensional (3D) model mimicking the in vivo biology of tumors. The PEGylated polyplexes thus prepared had a size of approximately 110 nm with clustered lactose moieties on their periphery as targeting ligands for the asialoglycoprotein-receptor-expressing HuH-7 cells. In contrast, OligofectAMINE/siRNA (cationic lipoplex) was observed to have almost no growth-inhibitory effect against HuH-7 spheroids, even though the lipoplex showed a stronger growth-inhibitory effect than the lac-PEGylated polyplexes on conventional monolayer-cultured HuH-7 cells. The FITC-tagged conjugate in the lac-PEGylated polyplexes showed smooth penetration into the HuH-7 spheroids compared with that in the lipoplexes, as observed by confocal fluorescence-scanning microscopy. This indicates that the small size of approximately 100 nm and the reduced nonspecific interaction due to the nonionic and hydrophilic lactosylated PEG layer contributes to the smooth penetration of the PEGylated polyplexes into the spheroid interior, eventually facilitating their uptake into the cells composing the spheroids. Cellular apoptosis indicating programmed cell death was also observed in the HuH-7 spheroids treated with the PEGylated polyplexes, revealing that the observed growth inhibition was indeed induced by the RNAi of the RecQL1 siRNA. These data suggest that the smart PEGylated polyplexes can indeed penetrate into the multiple cell layers of 3D tumor masses in vivo, exerting therapeutic effects through the RNAi.     

Quantum chemical molecular dynamics study of "shrinking" of hot giant fullerenes

We present a detailed analysis of size-down trajectories of the "Shrinking Hot Giant" road of fullerene formation, revealed before by our quantum chemical molecular dynamics simulations. It is found that shrinkage of giant fullerenes occurs in two stages, fall-off and pop-out stage, respectively, and that it is an irreversible process occurring naturally at high temperatures. The driving force behind the energetically unfavorable C2 evaporation is the increase in entropy and pi-conjugation stabilization of the increasingly more spherical fullerene cages. A comparison of the theoretical results with existing experimental data shows the importance of annealing for the synthesis of smaller (C60, C70) fullerenes.     

Stress-induced voiding in stacked tungsten via structure

The stress-induced voiding (SV) in Al-alloy films with stacked tungsten via structures was investigated. Voids were found in interconnections with stacked and borderless vias that had resistance increase after the aging tests. Failure occurs most frequently when the test structures are stored at approximately 250°C. This behavior can be explained by the diffusion creep model similar to SV in a flat line [1]. Finite-element simulations show that tensile stress in Al-lines between upper and lower plugs increases with temperature increase over 175°C. Al grains on W-plugs were found to have high-angle crystalline misorientation in transmission electron microscopy (TEM) observation. The tensile stress and grain misorientation should accelerate the void growth during high temperature storage. O₂ plasma post metal etch treatment is effective to eliminate SV in stacked via structure.     

The Potential Roles of Dec1 and Dec2 in Periodontal Inflammation

Periodontal inflammation is a common inflammatory disease associated with chronic inflammation that can ultimately lead to alveolar attachment loss and bone destruction. Understanding autophagy and pyroptosis has suggested their significant roles in inflammation. In recent years, studies of differentiated embryo-chondrocyte expressed genes 1 and 2 (Dec1 and Dec2) have shown that they play important functions in autophagy and in pyroptosis, which contribute to the onset of periodontal inflammation. In this review, we summarize recent studies on the roles of clock genes, including Dec1 and Dec2, that are related to periodontal inflammation and other diseases.     

Ethanolamine Is a New Anti-Prion Compound

Prion diseases are a group of fatal neurodegenerative disorders caused by accumulation of proteinaceous infectious particles, or prions, which mainly consist of the abnormally folded, amyloidogenic prion protein, designated PrP^Sc. PrP^Sc is produced through conformational conversion of the cellular isoform of prion protein, PrP^C, in the brain. To date, no effective therapies for prion diseases have been developed. In this study, we incidentally noticed that mouse neuroblastoma N2a cells persistently infected with 22L scrapie prions, termed N2aC24L1-3 cells, reduced PrP^Sc levels when cultured in advanced Dulbecco’s modified eagle medium (DMEM) but not in classic DMEM. PrP^C levels remained unchanged in prion-uninfected parent N2aC24 cells cultured in advanced DMEM. These results suggest that advanced DMEM may contain an anti-prion compound(s). We then successfully identified ethanolamine in advanced DMEM has an anti-prion activity. Ethanolamine reduced PrP^Sc levels in N2aC24L1-3 cells, but not PrP^C levels in N2aC24 cells. Also, oral administration of ethanolamine through drinking water delayed prion disease in mice intracerebrally inoculated with RML scrapie prions. These results suggest that ethanolamine could be a new anti-prion compound.     

Experimental verification of the effect of a voltage‐detection‐based shunt active filter for harmonic damping throughout a power distribution line

This paper is focused on a voltage‐detection‐based shunt active filter for installation on a power distribution system. A main objective of the active filter is to achieve damping of harmonic propagation coming from series/parallel resonance between capacitors for power factor correction and line inductors in the distribution system. The active filter installed at the end terminal of a distribution feeder is controlled in such a way as to present infinite impedance to the external circuit for the fundamental frequency, and to exhibit low resistance for harmonic frequencies. As a result, the active filter acts as a damping resistor for the harmonic propagation, like a 50‐Ω terminator installed at the end of a signal transmission line. It is verified by experiment that the active filter intended for harmonic termination has the capability of harmonic damping throughout the distribution feeder. © 2000 Scripta Technica, Electr Eng Jpn, 133(2): 1–10, 2000     

Response surface analysis of extract yield and flavour intensity of Brazilian cherry (Eugenia uniflora L.) obtained by supercritical carbon dioxide extraction

This work evaluated the effect of pressure and temperature on yield and characteristic flavour intensity of Brazilian cherry (Eugenia uniflora L.) extracts obtained by supercritical CO₂ using response surface analysis, which is a simple and efficient method for first inquiries. A complete central composite 2² factorial experimental design was applied using temperature (ranging from 40 to 60 °C) and pressure (from 150 to 250 bar) as independent variables. A second order model proved to be predictive (p ≤ 0.05) for the extract yield as affected by pressure and temperature, with better results being achieved at the central point (200 bar and 50 °C). For the flavour intensity, a first order model proved to be predictive (p ≤ 0.05) showing the influence of temperature. Greater characteristic flavour intensity in extracts was obtained for relatively high temperature (> 50 °C). Therefore, as far as Brazilian cherry is concerned, optimum conditions for achieving higher extract yield do not necessarily coincide to those for obtaining richer flavour intensity.Industrial relevanceSupercritical fluid extraction (SFE) is an emerging clean technology through which one may obtain extracts free from organic solvents. Extract yields from natural products for applications in food, pharmaceutical and cosmetic industries have been widely disseminated in the literature. Accordingly, two lines of research have industrial relevance, namely, (i) operational optimization studies for high SFE yields and (ii) investigation on important properties extracts are expected to present (so as to define their prospective industrial application). Specifically, this work studied the optimization of SFE process to obtain extracts from a tropical fruit showing high intensity of its characteristic flavour, aiming at promoting its application in natural aroma enrichment of processed foods.     

Recovery of population inversion in an erbium-doped fiber amplifier observed by temporally resolving amplified spontaneous emissions

We report on the recovery of population inversion in a CW-pumped erbium-doped fiber amplifier. Spontaneous emissions after the input of signal pulses were temporally resolved. The recovery time for population inversion was estimated to be a few hundred microseconds. The pump power and signal width dependences of the recovery were measured. We discuss the dependences by applying an analytical formula derived for the temporal evolution of population inversion.     

Experimental characterization of high-speed impact damage behavior in a three-dimensionally woven SiC/SiC composite

This paper discusses high-speed impact damage in a three-dimensionally woven SiC/SiC composite (3D-CMC). The impact damage was introduced by a steel ball projectile in 3D-CMC plates with and without thermal exposure. The surface and internal damages were observed by optical microscopy and X-ray CT. A crater was observed on the collision surface. The X-ray CT measurement revealed that multiple pyramid-shaped cone cracks were generated beneath the crater when the impact speed was relatively low. At an impact speed exceeding the critical speed, a spall fragment was ejected from the back surface, while no internal damage was observed in the fragment. The spall fracture mode differed between the virgin and the thermally-exposed specimens. This difference is the result of embrittlement of the fiber/matrix interface due to oxidation of the carbon coating layer in the thermally-exposed specimen. In addition, it is found that z-yarns improve impact resistance by constraining delamination.     

Blow-off process of highly under-expanded hydrogen non-premixed jet flame

Relationships between flame lift-off heights and reservoir pressure were experimentally investigated in order to clarify blow-off process of hydrogen non-premixed jet flames with a highly under-expanded jet structure. In this study, straight nozzles with diameters of 0.34, 0.53, 0.75 and 1.12 mm were used with maximum reservoir pressure for spouting hydrogen of 13.2 MPa. Experimental results are shown that lift-off heights in stable under-expanded jet flames do not vary significantly and are independent of the reservoir pressure in the range of studied pressure. However, the lifted heights are affected by the nozzle diameters and become smaller as the nozzle diameters increase. From experimental results, the condition for the blow-off process of under-expanded subsonic jet flames was proposed. It was concluded that the under-expanded jet flame could be blown off when the maximum waistline position, where radial distance from the jet axis to an elliptic stoichiometric contour reaches its maximum comes closer to the nozzle exit than the edge of the jet flame base.