Imaging of selective nuclear receptor modulator-induced conformational changes in the nuclear receptor to allow interaction with coactivator and corepressor proteins in living cells

Selective nuclear receptor modulators (SNRMs), which are used clinically for the treatment of NR-related diseases, display mixed agonistic/antagonistic activity in a tissue-selective manner depending on the cellular concentrations of coregulator proteins, that is, coactivators and corepressors. The molecular details of the SNRM function provided us with an idea for a rational method for the high-throughput screening of SNRMs in real time in intact living cells. We have developed genetically encoded fluorescent indicators based on the principle of ligand-induced coactivator and/or corepressor recruitment to NR ligand binding domain in single living cells. We demonstrated that an SNRM induces a distinct conformational change in the NR LBD, which is different from that induced by a full agonist or antagonist, but favorable for the recruitment of a coactivator or corepressor protein to the NR. The molecular details of an SNRM binding to a NR, and the subsequently induced conformational changes and recruitment of coregulator protein(s) are important features for the understanding of SNRM action in the living body. Our fluorescent indicators are capable of distinguishing among agonists, antagonists, and SNRMs, and can therefore serve as versatile molecular sensors that predict the pharmacological character of ligands, which is important for an accurate cure of a disease.     

Photo-induced valence tautomerism in Co complexes

A number of photofunctional molecular compounds have been developed recently. Typical examples of these are phototunable valence tautomeric compounds, which are now attracting great attention. When the charge-transfer bands of some Co valence tautomeric compounds are excited at low temperature, metastable redox isomers can be created after irradiation. The lifetimes of the metastable states can be more than several hours. These transformations can involve changes in the magnetic properties of the compounds, as well as their color. Hence, these compounds can be regarded as novel photomagnetic materials. The photoresponsive behaviors of these valence tautomeric compounds are similar to those of spin-crossover complexes (light-induced excited spin-state trapping effects).     

Dehydration of d-glucose in high temperature water at pressures up to 80 MPa

Reaction of d-glucose in water to yield 5-hydroxymethylfurfural (5-HMF), 1,2,4-benzenetriol (BTO) and furfural was studied at high temperatures (up to 400 °C) and high pressures (up to 80 MPa) using a continuous flow reactor. Maximum temperature and pressure conditions gave maximum furfural yield. Increasing pressure from 40 to 70 and 80 MPa enhanced dehydration reactions to 5-HMF, but also enhanced hydrolysis of 5-HMF leading to the production of BTO and thus lead to lower yields of 5-HMF (below 10%). Remarkably, the dehydration reaction to 5-HMF and the hydrolysis of 5-HMF were both enhanced by the increase in water density at 400 °C.     

Tuneable elastomeric nanochannels for nanofluidic manipulation

Fluidic transport through nanochannels offers new opportunities to probe fundamental nanoscale transport phenomena and to develop tools for manipulating DNA, proteins, small molecules and nanoparticles. The small size of nanofabricated devices and the accompanying increase in the effect of surface forces, however, pose challenges in designing and fabricating flexible nanofluidic systems that can dynamically adjust their transport characteristics according to the handling needs of various molecules and nanoparticles. Here, we describe the use of nanoscale fracturing of oxidized poly(dimethylsiloxane) to conveniently fabricate nanofluidic systems with arrays of nanochannels that can actively manipulate nanofluidic transport through dynamic modulation of the channel cross-section. We present the design parameters for engineering material properties and channel geometry to achieve reversible nanochannel deformation using remarkably small forces. We demonstrate the versatility of the elastomeric nanochannels through tuneable sieving and trapping of nanoparticles, dynamic manipulation of the conformation of single DNA molecules and in situ photofabrication of movable polymeric nanostructures.     

Fabrication of magnetic nanodot arrays for patterned magnetic recording media

Fabrication processes of arrayed magnetic nanodots for the use of patterned magnetic recording media were reviewed. One candidate for the patterned media is ordered assemble of magnetic nanoparticles, and the other is patterned magnetic thin films fabricated using various micro/nano scale machining processes. For the formation of patterned masks and molds, lithography processes as well as self-organized pattern formation are utilized. For the deposition processes of magnetic dots, electrochemical deposition processes were widely used. These fabrication processes are reviewed mainly from recent reports. The recording systems for the patterned media including probe-type-recording are also overviewed.     

Universal Test Interface for embedded-DRAM testing

Because the configurations of embedded DRAM macros vary for each product, designers normally must customize the test circuitry for each product. The authors have developed circuitry (Universal Test Interface) that unifies testing regardless of the DRAM configuration and the number of macros on a chip. The Universal Test Interface alleviates the contradiction inherent in embedded DRAM testing     

Dual roles of proteasome in the metabolism of presenilin 1

Presenilin 1 (PS1) has been identified as a causative gene for most early-onset familial Alzheimer's disease. Biochemical studies revealed that PS1 exists predominantly as two processed fragments in cells and brain tissues. We prepared stably transfected cells expressing the wild-type and familial Alzheimer's disease-associated mutants of PS1 and investigated the enzyme that participates in the metabolism of PS1. After treatment of the cells with proteasome inhibitors, the full-length PS1 was significantly accumulated. The levels of N- and C-terminal fragments were also increased. The accumulation of PS1 with a deletion of exon 10, which is unable to be processed, on treatment of the transfected cells with lactacystin indicated that proteasome can degrade full-length PS1. A synthetic peptide that includes the processing region of PS1 was cleaved by 20S proteasome at the putative processing sites after Met288 and Glu299. Metabolic labeling experiments showed that the appearance of the N-terminal fragment was attenuated by the inhibitor. Finally, 28-kDa N- and 20-kDa C-terminal fragments were generated by purified PS1 in vitro. These data indicated that the proteasome pathway is involved in PS1 processing. These results demonstrate that the proteasome pathway plays dual roles in processing and degradation of PS1.     

Lung abscess caused by Paecilomyces lilacinus

AIM: To present characteristics of heart and great vessel injuries in patients wounded during the 1992-1994 war in Bosnia and Herzegovina and their management in conditions of lack of complex diagnostic and therapeutic procedures. METHODS: Retrospective analysis was performed on the medical records of 31 patients treated for cardiac and great vessel injuries at the Department of Surgery, Tuzla University Hospital, between January 1992 and December 1994. RESULTS: The most frequent localization of the injuries was the right and left ventricles (each 10 cases), left atrium in 5, superior caval vein in 5, and inferior caval vein in 5 cases. Isolated pericardial injury was found in 5 cases. Immediately after injury, 22 injured suffered from shock, 7 from pericardial tamponade, and 2 were in a stable state. The mortality rate was 58%. Eight patients died during the operation as a consequence of bleeding. The highest mortality rate was recorded in the injuries of the left ventricle followed by the injuries of the in right ventricle and of superior caval vein. All 4 patients with multiple heart and great vessel injuries died. Mortality rate was significantly higher in patients who suffered from shock than in those who suffered from tamponade. CONCLUSIONS: Penetrating war injuries of heart and great vessels are among the most serious injuries in war. These injuries require prompt treatment to save life, but this is hardly manageable in hospitals without cardiopulmonary bypass facilities.     

All-optical discrimination based on nonlinear transmittance of MQWsemiconductor optical gates

This paper proposes an all-optical regenerator utilizing a novel all-optical discriminator. The impacts of nonlinearity of optical gates on discrimination performance are estimated. The evaluation of discrimination performance shows that amplified spontaneous emission noise and wave form distortion in optical signals can be effectively suppressed. We experimentally demonstrate the suppression using a low-temperature-grown optical switch up to 10 Gb/s     

A new hydrodealkylation process with fluid-beds to produce high purity naphthalene and methylnaphthalenes from heavy aromatic oils

By use of fluid-bed technology, direct hydrodealkylation of heavy oils was studied and a new process to produce high purity naphthalene and 2-methylnaphthalene was developed. As a basic research, catalyst activity, selectivity and stability for hydrodealkylation of heavy oil, hydrodealkylation reaction scheme and kinetics and coke formation kinetics and mechanism were investigated. Reaction rate constants were theoretically analyzed with fluid-bed consecutive reaction model. These research and analyses were utilized for optimization and design of the process. Pilot operation provided high yield and quality of the products which were suitable for synthesis of monomers for high performance polymers.