Towards a Treatment for Neuroinflammation in Epilepsy: Interleukin-1 Receptor Antagonist,Anakinra, as a Potential Treatment in Intractable Epilepsy

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a unique catastrophic epilepsy syndrome, and the development of drug-resistant epilepsy (DRE) is inevitable. Recently, anakinra, an interleukin-1 receptor antagonist (IL-1RA), has been increasingly used to treat DRE due to its potent anticonvulsant activity. We here summarized its effects in 38 patients (32 patients with FIRES and six with DRE). Of the 22 patients with FIRES, 16 (73%) had at least short-term seizure control 1 week after starting anakinra, while the remaining six suspected anakinra-refractory cases were male and had poor prognoses. Due to the small sample size, an explanation for anakinra refractoriness was not evident. In all DRE patients, seizures disappeared or improved, and cognitive function improved in five of the six patients following treatment. Patients showed no serious side effects, although drug reactions with eosinophilia and systemic symptoms, cytopenia, and infections were observed. Thus, anakinra has led to a marked improvement in some cases, and functional deficiency of IL-1RA was indicated, supporting a direct mechanism for its therapeutic effect. This review first discusses the effectiveness of anakinra for intractable epileptic syndromes. Anakinra could become a new tool for intractable epilepsy treatment. However, it does not currently have a solid evidence base.     

A DESIGN OF MULTILOOP PID CONTROLLERS WITH A NEURAL‐NET BASED DECOUPLER

In process industries, PID control schemes have been widely used due to their simple structures and easiness of comprehending the physical meanings of control parameters. However, the good control performance cannot be obtained by simply using PID controlschemes, since most processes are considered as nonlinear multivariable systems with mutual interactions. In this paper, a design method of multiloop PID controllers neural‐net based decoupler is proposed for nonlinear multivariable systems with mutual interactions. The proposed method consists of a decoupler given by the sum of a static decoupler and a neural‐net based decoupler, and multi‐loop PID controllers. Finally, the effectiveness of the proposed control scheme is evaluated on the simulation examples.     

Vehicle control algorithms for cooperative driving with automated vehicles and intervehicle communications

Describes the technologies of cooperative driving with automated vehicles and intervehicle communications in the Demo 2000 cooperative driving. Cooperative driving, aiming at the compatibility of safety and efficiency of road traffic, means that automated vehicles drive by forming a flexible platoon over a couple of lanes with a short intervehicle distance while performing lane changing, merging, and leaving the platoon. The vehicles for the demonstration are equipped with automated lateral and longitudinal control functions with localization data by the differential global positioning system (DGPS) and the intervehicle communication function with 5.8-GHz dedicated short range communication (DSRC) designed for the dedicated use in the demonstration. In order to show the feasibility and potential of the technologies, the demonstration was held in November 2000, on a test track with five automated vehicles. The scenario included stop and go, platooning, merging, and obstacle avoidance.     

Design and prototyping of micro centrifugal compressor for ultra micro gas turbine

In order to establish the design methodology of an ultra micro centrifugal compressor, which is the most important component of an ultra micro gas turbine unit, a 10 times size of the final target compressor (impeller outer diameter 40 mm, corrected rotational speed 220,000 r/min) was designed. The problems to be solved for downsizing were examined and a 2-dimensional impeller was chosen as the first model due to its productivity. The conventional ID prediction method and CFD were used. The prototyped compressor was tested by using cold air at the reduced speed of 110,000 r/min. Following to the 10 times model, a 5 times size of the final target model having fully 3-dimensional shape (impeller outer diameter 20mm, corrected rotational speed 500,000 r/min) was designed and tested by using hot gas at the reduced speed of 250,000 r/min.     

Fabrication of Sr0.5Ba0.5Nb2O6 Nanocrystallite‐Precipitated Transparent Phosphate Glass‐Ceramics

Transparent (Sr_0.5Ba_0.5)Nb₂O₆ (SBN50) nanocrystallite‐precipitated phosphate glass‐ceramics were prepared by a conventional glass‐ceramic process. x(SrO–BaO–2Nb₂O₅) ? (100–4x)P₂O₅ (xSBNP) glasses with a refractive index of 1.9–2.0 exhibited high water resistance owing to the presence of Q⁰ and Q¹ phosphate units. Both bulk and surface crystallization of the SBN50 phase were observed in 20SBNP and 21SBNP glass‐ceramics. Although the nominal content of SBN50 crystals in the 21SBNP glass was larger than that in the 20SBNP glass, the latter exhibited better crystallinity of SBN50 and a higher number density of precipitated SBN nanocrystallites. By tuning the two‐step heat‐treatment and the chemical composition, transparent SBN50‐precipitated glass‐ceramics were successfully obtained. Given that no remarkable increase of the relative dielectric constants was observed after crystallization of the SBN50 nanocrystallites, it is postulated that the relative dielectric constant of the bulk is mainly governed by the amorphous phosphate region, and that the contribution of precipitation of the SBN50 nanocrystallites to the dielectric constant is not very significant in this system.     

Thrombin Receptor-Activating Protein (TRAP)-Activated Akt Is Involved in the Release of Phosphorylated-HSP27 (HSPB1) from Platelets in DM Patients

It is generally known that heat shock protein 27 (HSP27) is phosphorylated through p38 mitogen-activated protein (MAP) kinase. We have previously reported that HSP27 is released from human platelets associated with collagen-induced phosphorylation. In the present study, we conducted an investigation into the effect of thrombin receptor-activating protein (TRAP) on the release of HSP27 in platelets in type 2 diabetes mellitus (DM) patients. The phosphorylated-HSP27 levels induced by TRAP were directly proportional to the aggregation of platelets. The levels of phosphorylated-HSP27 (Ser-78) were correlated with the levels of phosphorylated-p38 MAP kinase and phosphorylated-Akt in the platelets stimulated by 10 µM TRAP but not with those of phosphorylated-p44/p42 MAP kinase. The levels of HSP27 released from the TRAP (10 µM)-stimulated platelets were correlated with the levels of phosphorylated-HSP27 in the platelets. The released platelet-derived growth factor-AB (PDGF-AB) levels were in parallel with the HSP27 levels released from the platelets stimulated by 10 µM TRAP. Although the area under the curve (AUC) of small aggregates (9–25 µm) induced by 10 µM TRAP showed no significant correlation with the released HSP27 levels, AUC of medium aggregates (25–50 µm), large aggregates (50–70 µm) and light transmittance were significantly correlated with the released HSP27 levels. TRAP-induced phosphorylation of HSP27 was truly suppressed by deguelin, an inhibitor of Akt, in the platelets from a healthy subject. These results strongly suggest that TRAP-induced activation of Akt in addition to p38 MAP kinase positively regulates the release of phosphorylated-HSP27 from human platelets, which is closely related to the platelet hyper-aggregation in type 2 DM patients.     

Fabrication of flat micro‐gap electrodes for molecular electronics

Recently, organic molecular electronic devices such as molecular thin‐film transistors have received considerable attention as possible candidates for next‐generation electronic and optical devices. This paper reports on fabrication technologies of flat metallic electrodes on insulating substrates with a micrometer separation for high‐performance molecular device evaluation. The key technologies of fabricating planar‐type electrodes are the liftoff method by the combination of bilayer photoresist with overhang profile, electron beam evaporation of thin metal (Ti and Au) films, and SiO₂‐CMP (Chemical Mechanical Polishing) method of CVD (Chemical Vapor Deposition)‐deposited TEOS (tetraethoxysilane)–SiO₂ layer. The raggedness of the electrode/insulator interface and the electrode surface of the micro‐gap electrodes were less than 3 nm. The isolation characteristics of fabricated electrodes were on the order of 10¹³ ohms at room temperature, which is sufficient for evaluating electronic properties of organic thin‐film devices. Finally, pentacene FET (Field Effect Transistor) characteristics are discussed fabricated on the micro‐gap flat electrodes. The mobility of this FET was 0.015 cm²/Vs, which was almost on the order of the previous results. These results suggest that high‐performance organic thin‐film transistors can be realized on these advanced electrode structures. © 2005 Wiley Periodicals, Inc. Electr Eng Jpn, 152(2): 39–46, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20152     

Back-illuminated pulse-frequency-modulated photosensor using silicon-on-sapphire technology developed for use as epi-retinal prosthesis device

An intra-ocular epi-retinal prosthesis device using a back-illuminated photosensor is proposed and demonstrated for the first time. The photosensor, based on a pulse frequency modulation, is fabricated on a transparent sapphire substrate to detect the backside incident light. Experimental results show that the device is sensitive over a dynamic range of incident light of 30 dB.     

Pulse frequency modulation based CMOS image sensor for subretinal stimulation

We have developed a CMOS image sensor based on pulse frequency modulation for subretinal implantation. The sensor chip forms part of the proposed intraocular retinal prosthesis system where data and power transmission are provided wirelessly from an extraocular unit. Image sensing and electrical stimulus are integrated onto the same chip. Image of sufficient resolution has been demonstrated using 16/spl times/16 pixels. Biphasic current stimulus pulses at above threshold levels of the human retina (500 /spl mu/A) at varying frame rates (4 Hz to 8 kHz) have been achieved. The implant chip was fabricated using standard CMOS technology.     

A 100-mega-access per second matching memory for a data-drivenmicroprocessor

A high-throughput matching memory (MM) for a data-driven microprocessor is discussed. An MM can be constructed using a hashing memory. However, one of the biggest problems with hashing memory is the necessity for selective processing whenever hashed address conflicts occur. To eliminate this problem, the MM incorporated a small amount of associative memory (32 words×50 b) as well as the hashing memory (512 words×42 b). The matching operation is subdivided into three pipeline stages, all controlled by the elastic pipeline scheme. With this structure, an MM with a high throughput of 100-mega-access/s MM can be realized