Peroxiredoxin 2 as a chemotherapy responsiveness biomarker candidate in osteosarcoma revealed by proteomics

Purpose : We aimed to identify novel chemotherapy responsiveness biomarkers for osteosarcoma (OS) by investigating the global protein expression profile of 12 biopsy samples from OS patients. Experimental design : Six patients were classified as good responders and six as poor responders, according to the Huvos grading system. The protein expression profiles obtained by 2‐D DIGE consisted of 2250 protein spots. Results : Among them, we identified 55 protein spots whose intensity was significantly different (Bonferroni adjusted p‐value<0.01) between the two patient groups. Mass spectrometric protein identification demonstrated that the 55 spots corresponded to 38 distinct gene products including peroxiredoxin 2 (PRDX 2). Use of a specific antibody against PRDX 2 confirmed the differential expression of PRDX 2 between good and poor responders, while PRDX 2 levels as measured by Western blotting correlated highly with their corresponding 2‐D DIGE values. The predictive value of PRDX 2 expression was further confirmed by examining an additional four OS cases using Western blotting. Conclusions and clinical relevance : These results establish PRDX 2 as a candidate for chemotherapy responsiveness marker in OS. Measuring PRDX 2 in biopsy samples before treatment may contribute to more effective management of OS.     

Probability of graphs with large spectral gap by multicanonical Monte Carlo

Graphs with large spectral gap are important in various fields such as biology, sociology and computer science. In designing such graphs, an important question is how the probability of graphs with large spectral gap behaves. A method based on multicanonical Monte Carlo is introduced to quantify the behavior of this probability, which enables us to calculate extreme tails of the distribution. The proposed method is successfully applied to random 3-regular graphs and large deviation probability is estimated.     

Parametric embedding for class visualization

We propose a new method, parametric embedding (PE), that embeds objects with the class structure into a low-dimensional visualization space. PE takes as input a set of class conditional probabilities for given data points and tries to preserve the structure in an embedding space by minimizing a sum of Kullback-Leibler divergences, under the assumption that samples are generated by a gaussian mixture with equal covariances in the embedding space. PE has many potential uses depending on the source of the input data, providing insight into the classifier's behavior in supervised, semisupervised, and unsupervised settings. The PE algorithm has a computational advantage over conventional embedding methods based on pairwise object relations since its complexity scales with the product of the number of objects and the number of classes. We demonstrate PE by visualizing supervised categorization of Web pages, semisupervised categorization of digits, and the relations of words and latent topics found by an unsupervised algorithm, latent Dirichlet allocation.     

Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells

This study explored the use of interleukin 2 (IL-2) and interferon gamma (IFN-gamma) gene-modified tumor cells as cellular vaccines for the treatment of bladder cancer. The mouse MBT-2 tumor used is an excellent model for human bladder cancer. This carcinogen-induced tumor of bladder origin resembles human bladder cancer in its etiology and histology, and responds to treatment in a manner similar to its human counterpart. Using retroviral vectors, the human IL-2 and mouse IFN-gamma genes were introduced and expressed in MBT-2 cells. The tumor-forming capacity of the cytokine gene-modified MBT-2 cells was significantly impaired, since no tumors formed in mice injected intradermally with either IL-2- or IFN-gamma-secreting cells, using cell doses far exceeding the minimal tumorigenic dose of parental MBT-2 cells. Furthermore, mice that rejected the IL-2- or IFN-gamma-secreting tumor cells became highly resistant to a subsequent challenge with parental MBT-2 cells, but not to 38C13 cells, a B cell lymphoma of the same genetic background. To approximate the conditions as closely as possible to the conditions prevailing in the cancer patient, inactivated cytokine-secreting cells were used to treat animals bearing tumors established by orthotopic implantation of MBT-2 cells into the bladder wall of the animal. Treatment of mice carrying a significant tumor burden with IL-2-secreting MBT-2 cells had a significant inhibitory effect on tumor progression with extended survival. Moreover, in 60% of the mice the tumor regressed completely and the animals remained alive and free of detectable tumor for the duration of the observation period. Treatment of tumor-bearing animals with IL-2-secreting MBT-2 cells was superior to the use of cisplatin, a chemotherapeutic agent used in the treatment of bladder cancer. The therapeutic effect of IFN-gamma-secreting cells was minimal and treatment with unmodified MBT-2 cells had no effect on tumor growth or survival, showing that the parental MBT-2 cells were nonimmunogenic in this experimental setting. Most importantly, mice that exhibited complete tumor regression after treatment with IL-2-secreting MBT-2 cells became resistant to a subsequent challenge with a highly tumorigenic dose of parental MBT-2 cells, indicating that long-term immunological memory was established in the "cured" mice.     

Chemical and electrochemical preparation of poly(9,10-dihydrophenanthrene-2,7-diyl) using nickel complexes and electrochemical properties of the polymer

Summary Dehalogenation polycondensations of 2,7-dibromo-9,10-dihydrophenanthrene with isolated zero-valent nickel complex and electrochemically generated zero-valent nickel complex afford -conjugated poly(9,10-dihydrophenanthrene-2,7-diyl). The electrochemically synthesized polymer is obtained as a thin film on electrode, and shows a reversible electrochemically doping-undoping cycle in an oxidation region. The polymer has essentially the same -conjugation system as that of poly(p-phenylene).     

A novel method for measuring direct compressive properties of carbon fibres using a micro-mechanical compression tester

A novel method has been developed for measuring direct compressive properties such as strength and elasticity of a series of mesophase-pitch-based and PAN-based carbon fibres about 10 m in diameter by uniaxial and transverse compression tests using a micromechanical tester. The fibres were shaped into cylindrical specimens, with their size ratio of length to diameter kept at about 2 to 3, by separating them from a thin film made by polishing the cut faces of a strand of carbon fibres with epoxy resin as a matrix. Individual cylindrical specimens were stood up or laid down on a glass plate without any fixer for the measurements of axial and transverse compression properties of fibres, respectively. The fibres exhibited non-linear elasticity, with the compressive modulus decreasing with compressive deformation. The direct axial compressive strengths of pitch-based carbon fibres were found to be marginally lower than the indirect ones, whereas there was no significant difference between the two strength values for PAN-based fibres. The pitch-based fibres exhibited smaller average values of axial compressive strength than the PAN-based fibres. The transverse compressive strength, which decreases with an increase in elasticity of carbon fibres, exhibited a considerably lower average value than that of the axial compressive strength. Further, the axial compressive strength was found to be smaller than the direct tensile strength for the fibres.     

Mode matching for a passive resonant ring laser gyroscope

An analytical method of matching the mode of an input laser to the lowest-order mode of a passive resonant ring laser gyro is described, as are the steps in determining the location and focal length of cylindrical mode matching lenses. Results were obtained with no mode matching, with a compromise spherical lens, with horizontal mode matching only, and with the proper cylindrical mode matching lenses. Compared with no mode matching, the latter case shows that the amplitude of the lowest-order mode is increased approximately 2.5 times. In addition, the number and intensity of higher-order modes are reduced to near zero, and the relative intensity of the lowest-order mode to the higher-order mode increased from approximately 5 to approximately 60 times greater.     

Secondary electron emission and surface charging evaluation of alumina ceramics and sapphire

The breakdown of alumina rf windows is mostly caused by multipactor, as well as by material defects and contamination. Since multipator induces localized surface heating, leading to surface melting, it is necessary to observe secondary electron emission (SEE) coefficients of alumina ceramics under high temperature conditions. The SEE coefficients of commercial alumina ceramics and sapphire were measured by a scanning electron microscopy (SEM) with a single short-pulsed electron beam (100 pA, 1 ms) at room temperature and at 650degC. Additive materials used for sintering alumina, such as SiO ₂ and MgO, were also investigated. Surface charging evaluations have also become important because the accumulated charges are discharged at the threshold Held, resulting in surface discharge. The surface charging evaluations were carried out by multi-pulse measurements with the injection of successive pulses on the sample. As a result, reductions in the SEE coefficients with temperature were confirmed, except for sapphire. The multi-pulse measurement results indicated that surface charging of the sapphire was higher than that of other samples. This may be one of the factors that causes sapphire not to be durable for rf window applications, compared with alumina ceramics. Although there are few exceptions, it was found that the SEE coefficients of alumina ceramics increased with the purity and the average grain size     

Demonstration of 13.56-MHz class-E amplifier using a high-Voltage GaN power-HEMT

A 13.56-MHz class-E amplifier with a high-voltage GaN HEMT as the main switching device is demonstrated to show the possibility of using GaN HEMTs in high-frequency switching power applications such as RF power-supply applications. The 380-V/1.9-A GaN power HEMT was designed and fabricated for high-voltage power-electronics applications. The demonstrated circuit achieved the output power of 13.4 W and the power efficiency of 91% under a drain-peak voltage as high as 330 V. This result shows that high-voltage GaN devices are suitable for high-frequency switching applications under high dc input voltages of over 100 V.