A Smart Hyperthermia Nanofiber-Platform-Enabled Sustained Release of Doxorubicin and 17AAG for Synergistic Cancer Therapy

This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery.     

Radiation therapy for stage I-II non-small cell lung cancer in patients aged 75 years and older

Vaccination with peptides that induce a specific immune response is a potential prophylactic or therapeutic strategy against viral infections and tumors. Because of the extensive polymorphism of the HLA loci, synthetic peptide vaccines must consist of a cocktail of peptides that bind specifically to different HLA molecules. Such cocktails should be optimized for the target population as each population has its specific HLA gene frequencies. To achieve maximum population coverage with a minimum number of peptides, information is needed on the ranking of the most frequent HLA phenotypes. We introduce the minimal phenotype panel, which is the smallest combination of HLA antigens selected so that the proportion of individuals in a population that express at least one of the antigens in the panel exceeds a desired minimum value. We developed a method for assembling minimal phenotype panels based on known HLA class I gene frequencies. We give an example based on a set of 2446 well-defined HLA-typed, random, healthy, unrelated, Dutch Caucasoid individuals. In addition, we discuss the possibility of assembling minimal phenotype panels based on two-locus haplotypes, which enables the assembly of phenotype panels from the antigens of both loci.     

An image analyzing system using an artificial neural network forevaluating the parenchymal echo pattern of cirrhotic liver and chronichepatitis

To objectively evaluate the parenchymal echo pattern of cirrhotic liver and chronic hepatitis, the authors applied an image analyzing system (IAS) using a neural network. Autopsy specimens in a water tank (n=13) were used to examine the relationship between the diameter of the regenerative nodule and the coarse score (CS) calculated by IAS. CS was significantly correlated with the diameter of the regenerative nodule (p<0.0001, r=0.966). CS is considered to be useful for evaluating the coarseness of the parenchymal echo pattern     

Ergonomics solution for crossing collisions based on field assessment of visual environment at urban intersections in Japan

This paper aims to assess quantitatively the actual visual environment of uncontrolled urban downtown intersections in Japan in relation to frequently occurring crossing collisions and to discuss the safety countermeasures for them. In Field Study 1 dealing with direct visibility, our ultra-wide-angle photograph analysis revealed that most of the right/left-ward visible range at 11 intersections were insufficient to check safety, and the quality of direct visibility was closely associated with causing crossing collisions. The countermeasures to reduce a blind area were determined to be a top priority. In Field Study 2 dealing with indirect visibility, more than half of the 25 traffic convex mirrors had marked shortcomings for preventive safety, and ergonomics guidelines ensuring indirect visibility were proposed for installing traffic convex mirrors. Low-cost/low-technology-oriented countermeasures are highly recommended to obtain clear/sufficient images of crucial information satisfying drivers' requirements on traffic convex mirrors in accordance with those ergonomics guidelines was highly recommended. Crossing collisions could be prevented by improvement of poor direct and indirect visibility.     

Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl

We have generated transgenic mice over-expressing human apolipoprotein CI (apo CI) using the native gene joined to the downstream 154-bp liver-specific enhancer that we defined for apo E. Human apo CI (HuCI)-transgenic mice showed elevation of plasma triglycerides (mg/dl) compared to controls in both the fasted (211 +/- 81 vs 123 +/- 52, P = 0.0001) and fed (265 +/- 105 vs 146 +/- 68, P < 0.0001) states. Unlike the human apo CII (HuCII)- and apo CIII (HuCIII)-transgenic mouse models of hypertriglyceridemia, plasma cholesterol was disproportionately elevated (95 +/- 23 vs 73 +/- 23, P = 0.002, fasted and 90 +/- 24 vs 61 +/- 14, P < 0.0001, fed). Lipoprotein fractionation showed increased VLDL and IDL + LDL with an increased cholesterol/triglyceride ratio (0.114 vs 0.065, P = 0.02, in VLDL). The VLDL apo E/apo B ratio was decreased 3.4-fold (P = 0.05) and apo CII and apo CIII decreased in proportion to apo E. Triglyceride and apo B production rates were normal, but clearance rates of VLDL triglycerides and postlipolysis lipoprotein "remnants" were significantly slowed. Plasma apo B was significantly elevated. Unlike HuCII- and HuCIII-transgenic mice, VLDL from HuCI transgenic mice bound heparin-Sepharose, a model for cell-surface glycosaminoglycans, normally. In summary, apo CI overexpression is associated with decreased particulate uptake of apo B-containing lipoproteins, leading to increased levels of several potentially atherogenic species, including cholesterol-enriched VLDL, IDL, and LDL.     

Fabrication of micro-gelatin fiber utilizing coacervation method

Biotechnology has drastically been advanced by the development of iPS and ES cells, which are representative forms induced pluripotent stem cells. In the micro/nano bio field, the development of cells and Taylor-made medicine for a potential treatment of incurable diseases has been a center of attention. The melting point of gelatin is between 25 and 33 °C, and the sol–gel transition occurs in low temperature. This makes the deformation of this useful biomaterial easy. The examples of gelatin fiber applications are suture threads, blood vessel prosthesis, cell-growth-based materials, filter materials, and many others. Because the cell size differs depending on the species and applications, it is essential to fabricate gelatin fibers of different diameters. In this paper, we have developed a fabrication method for gelatin fibers the coacervation method. We fabricated narrow gelatin fibers having a diameter over 10 μm.     

Closed loop identification and control loop reconfiguration: an industrial case study

The results of a joint university–industry collaborative project for control loop reconfiguration using closed loop experimental data from a fuel gas pressure control system are described in this paper. The fuel gas pressure was being regulated using a butane stream. For economic reasons, it was necessary to switch control to the ethane stream. Previous attempts at effecting this changeover had proved unsuccessful. In this study, a powerful system identification technique namely Canonical Variate Analysis (CVA) was employed to obtain the empirical plant models. A PI controller was then designed using the direct synthesis method. Acceptable closed loop behavior was obtained with little online tuning.     

Production of eicosapentaenoic acid by a recombinant marine cyanobacterium, Synechococcus sp.

The eicosapentaenoic acid (EPA) synthesis gene cluster from an EPA-producing bacterium, Shewanella sp. SCRC-2738, was cloned into a broad-host range vector, pJRD215, and then introduced into a marine cyanobacterium, Synechococcus sp. NKBG15041c, by conjugation. The transconjugant cyanobacteria produced 3.7±0.2% (2.24±0.13 mg/L) EPA (n-3) and 2.5 ±0.2% (1.49±0.06 mg/L) eicosatetraenoic acid (n-3) of the total fatty acids when the cells were cultured at 23°C at a light intensity of 1,000–1,500 Lux. The EPA and eico-satetraenoic acid contents of the cells were increased to 4.6±0.6% (3.86±1.11 mg/L) and 4.7±0.3% (3.86±0.82 mg/L), and 7.5±0.3% (1.76±0.10 mg/L) and 5.1±0.2% (1.19±0.06 mg/L) when they were cultured at low temperature (18°C) and at lower light intensity (40 Lux), respectively.     

Novel vitamin E derivative with 4-substituted resorcinol moiety has both antioxidant and tyrosinase inhibitory properties

A novel vitamin E derivative, (6″-hydroxy-2″,5″,7″,8″-tetramethylchroman-2″-yl) methyl 3-(2′,4′-dihydroxyphenyl)propionate (TM4R), which has a chromanoxyl ring and 4-substituted resorcinol moieties, was synthesized; and its inhibitory effects on tyrosinase, antioxidant ability, and lightening effect of ultraviolet B (UVB)-induced hyperpigmentation were estimated. TM4R showed potent inhibitory activity on tyrosinase, which is the rate-limiting enzyme in melanogenesis. The scavenging activities of TM4R on 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radicals were found to be nearly the same as those of α-tocopherol. Furthermore, an efficient lightening effect was observed following topical application of TM4R to UVB-stimulated hyperpigmented dorsal skin of brownish guinea pigs. These results suggest that TM4R may be a candidate for an efficient whitening agent, possibly by inhibiting tyrosinase activity and biological reactions caused by reactive oxygen species.     

On the heat removal characteristics and the analytical model of a thermal energy storage capsule using gelled Glauber's salt as the PCM

An analytical and experimental investigation was performed on a heat removal process of the thermal energy storage (TES) capsule, using gelled Glauber's salt. Transient heat flux at the capsule wall was measured for various cooling conditions. In cases where the initial temperature was lower than the saturation temperature of the phase change material (PCM), numerical analyses were performed, approximating the process by a relaxation phenomenon where crystals grew around crystal nuclei. The results of the numerical solution agreed very well with the experimental results.