Characterization of a cartilage-derived 66-kDa protein (RGD-CAP/beta ig-h3) that binds to collagen

Malignant human gliomas are the most common forms of primary tumors in the central nerve system. Due to their location and invasive nature, treatment so far has been mainly palliative. Thus, understanding the molecular detail of tumor transformation and progression is crucial for developing effective therapeutic strategy for this fetal tumor. Among the genetic alternations found in these tumors, p53 inactivation and PDGF/PDGFR activation represent the early events, and the loss of chromosome 10 and gene amplification and rearrangement of EGFR represent the late events. Studies with both glioma cell lines and primary tumor tissues have strongly suggested that TGF-alpha and EGFR function as an important autocrine loop in supporting proliferation of human glioma, especially in high grade glioma, since elevated TGF-alpha expression is also found in these high grade tumors. Furthermore, down regulation of the expression of TGF-alpha by antisense constructs has been shown to inhibit several types of human tumor cell growth including glioma. Other means of therapeutic approaches using this autocrine loop as a target also include the use of monoclonal antibodies and their cytotoxic conjugated. Considerable understanding of the EGFR-mediated signal transduction pathways has become available recently, which including GRB2/mSOS1 mediated MAP kinase activation; JAK/STATs pathway; PLC-gamma pathway. However, much work still needs to be done before a specific component of these pathways can be applied for effective control of tumor growth in the clinic.     

Synchronization of pulsed Tksapphire lasers and its application to difference frequency mixing for tunable infrared generation

A simple and effective technique for synchronizing two independent Ti: sapphire lasers was developed and used for difference-frequency generation. By control of pump intensity, buildup times of these lasers were adjusted to coincide for any combination of wavelengths that was needed for the production of a desired difference frequency. Synchronized pulses were mixed at a AgGaS(2) crystal, producing infrared pulses from 6.2 to 9.7 μm. Characteristic features of the method as well as its possible extension of the tuning range are discussed.     

An application of the 2-nitrobenzenesulfenyl method to proteomic profiling of human colorectal carcinoma: A novel approach for biomarker discovery

In the development of novel biomarkers, the proteomic approach is advantageous because using it the cancer-associated proteins can be directly identified. We previously developed a 2-nitrobenzenesulfenyl (NBS) method to improve quantitative proteome analysis. Here, we applied this method to proteomic profiling of colorectal carcinoma (CRC) to identify novel proteins with altered expression in CRC. Each pair of tumor and normal tissue specimens from 12 CRC patients was analyzed, and approximately 5000 NBS-labeled paired peaks were quantified. Peaks with altered signal intensities (>1.5-fold) and occurring frequently in the samples (>70%) were selected, and 128 proteins were identified by MS/MS analyses as differentially expressed proteins in CRC tissues. Many proteins were newly revealed to be CRC related; 30 were reported in earlier studies of CRC. Six proteins that were up-regulated in CRC (ZYX, RAN, RCN1, AHCY, LGALS1, and VIM) were further characterized and validated by Western blot and immunohistochemistry. All six were found to be CRC-localized, either in cancer cells or in stroma cells near the cancer cells. These results indicate that the proteins identified in this study are novel candidates for CRC markers, and that the NBS method is useful in proteome mining to discover novel biomarkers.     

Field Investigation of Soil Heave by a Large Diameter Chilled Gas Pipeline Experiment, Fairbanks, Alaska

A large scale 105-m-long, 0.9-m-diam chilled pipeline experiment was conducted to assess the response of a production pipeline that transits between unfrozen (seasonally frozen) and permafrost soils in discontinuous permafrost regions. Thermal and heave characteristics of the experiment for a three-year monitoring period are reported. In response to the chilled pipeline, the progressive cooling patterns within the permafrost and unfrozen soils were different, resulting in the development of a thermal boundary at the transition zone between the two thermally different soils. The absolute maximum movement of pipeline was 0.197 m near the thermal boundary, resulting in a differential heave of 0.148 m. Three distinct heave phases were identified within the unfrozen soil. Phase 1 of the first 200 days related to penetration and heave above the groundwater table and was characterized by heave rates between 0.211 and 0.237 mm/day. Phase 2 resulted in increased ice segregation due to interaction of the freez-ing front with the groundwater table. This phase lasted from approximately day200 to day 500 and corresponded to a heave rate from 0.206 to 0.313 mm/day. Phase 3 was characterized by a further decrease in the heave rate to about 0.081 mm/day and lasted from approximately day 500 to day 1,056.     

Intermittent administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and prevents pancreatic exhaustion in diabetic mice

We previously demonstrated that repetitive administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and energy expenditure in obese diabetic db/db mice. However, we have not evaluated in detail the effect of single or intermittent BDNF administration on glucose metabolism in a diabetic animal model. The objectives of this study were to examine the dose-response effect and dosing interval of BDNF administration in db/db mice and to evaluate the effect of intermittent BDNF administration on pancreatic function in db/db mice. We evaluated the dose-response effect of BDNF by single administration in db/db mice. First, single administration of BDNF greater than 70 mg/kg significantly reduced blood glucose concentration one day after administered, and the BDNF effect was maintained for 6 d. Next, the effects of BDNF administered twice a week at 4, 10, 25, and 62.5 mg/kg on blood glucose concentration, and the effects of BDNF administered once a week at 10, 20, 30, 50, and 70 mg/kg on blood glucose concentration were examined in db/db mice. In the intermittent treatment studies, BDNF dose-dependently ameliorated glucose metabolism by not only the twice-a-week administration but also the once-a-week administration. Lastly, because BDNF reduces the food intake of obese hyperphagic diabetic mice, the effects of BDNF administered once or twice a week on the blood glucose concentration and plasma and pancreatic insulin concentrations in db/db mice were compared with those of the vehicle under pair-fed conditions. Under pair-fed conditions, the intermittent administration of BDNF (25 mg/kg, twice a week, or 50 mg/kg, once a week) significantly reduced the blood glucose concentration and increased the plasma and pancreatic insulin concentrations compared with those in the pair-fed vehicle-treated db/db mice. This indicates that the prolonged hypoglycemic effect of BDNF is not simply due to the reduction of food intake. In conclusion, we demonstrated that the intermittent administration of BDNF ameliorates glucose metabolism and prevents pancreatic exhaustion in obese diabetic mice. These findings indicate that BDNF may have potential as a unique hypoglycemic agent for the treatment of diabetes at a fundamental level with good patient compliance.     

In-Plane Anisotropy of the Upper Critical Field of La2−x Sr x CuO4 in the Underdoped and Overdoped Regimes

For La_2–x Sr _x CuO₄ single-crystals in the underdoped and overdoped regimes, we have measured the electrical resistivity along the c-axis, _c , under constant magnetic fields, changing the field direction in the ab-plane. At x=0.08, 0.12 and 0.16 in the underdoped and almost optimally-doped regimes, clear anisotropy of _c with the fourfold symmetry in the ab-plane has been observed. This symmetry is regarded as the fourfold symmetry of the upper critical field, H _c2, and explained as being mainly due to the anisotropy of the superconducting energy gap owing to the d_x ^{2-y 2} pairing. The magnitude of the fourfold component of H _c2, H _c2/H _c2, is largest in x=0.08 among the three crystals. At x=0.20 in the overdoped regime, no clear fourfold symmetry has been observed. It appears that the fourfold symmetry is easy to observe in the underdoped regime rather than in the overdoped regime.     

Improvement of fracture properties of hydroxyapatite particle filled poly(l-lactide)/poly(ε-caprolactone) biocomposites using lysine tri-isocyanate

Effects of LTI addition on the mode I fracture energy of HA/PLLA/PCL were examined and the micro-structural modification due to LTI addition was investigated. Both the mode I energy release rate, G _in, and averaged fracture energy, E _f, are improved dramatically due to LTI addition. The reason is considered to be the improvements of the interfacial structure connecting HA particles with PLLA/PCL matrix and the miscibility between PLLA and PCL. These changes of blend morphology and interfacial structure reduce the stress concentration and lead to the ductile deformation and resulted in the increase of those fracture properties.     

Selective conversion of CO into methanol at ordinary temperature, part 5. Using an electrochemical photocell

Carbon monoxide has been selectively converted to methanol by means of an electrochemical photocell composed of the n-CdS photoanode and the Everitt's salt-modified platinum cathode. The catholyte was the CO-saturated aqueous solution containing a metal complex and a primary alcohol operating as homogeneous catalysts. In the anolyte, various reducing agents were added to reduce the holes created at the semiconductor. The current efficiency of the methanol formation was almost 100%, irrespective of the kind of metal complex if the reducing agent added as a hole scavenger to the anolyte has a sufficiently negative redox potential.     

Relationship between microstructure and fracture behavior of bioabsorbable HA/PLLA composites

Hydroxyapatite particles of four different shapes, that is, micro, nano, spherical and plate, were used to fabricate hydroxyapatite filled poly(l-lactic acid) (HA/PLLA) composites. Effects of HA particle shape on the fracture behavior of HA/PLLA were investigated by mode I fracture testing, fracture surface measurement and scanning electron microscopy. It was found that the micro-HA/PLLA has the highest critical energy release rate, G_IC, with the largest surface roughness, while G_IC of the nano-HA/PLLA was lowest corresponding to the smallest surface roughness. The micro-HA/PLLA composites exhibited interfacial debonding and local ductile deformation of the PLLA matrix, indicating higher fracture energy and therefore, the highest G_IC. On the other hand, the nano-HA/PLLA composites showed brittle fracture surface due to nano-scale interaction between PLLA fibrils and primary HA particles, corresponding to lower fracture energy and hence the lowest G_IC.