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Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as chromosomal damage and molecular alterations. There is no doubt that many factors influence the responses of people to radiation to different degrees. In addition to the obvious general factors of radiation quality, dose, dose rate and the tissue (sub)volume irradiated, recognized and potential determining factors include age, sex, life style (e.g., smoking, diet, possibly body mass index), environmental factors, genetics and epigenetics, stochastic distribution of cellular events, and systemic comorbidities such as diabetes or viral infections. Genetic factors are commonly thought to be a substantial contributor to individual response to radiation. Apart from a small number of rare monogenic diseases such as ataxia telangiectasia, the inheritance of an abnormally responsive phenotype among a population of healthy individuals does not follow a classical Mendelian inheritance pattern. Rather it is considered to be a multi-factorial, complex trait.

Background Although early reperfusion is the most desirable intervention after ischemic myocardial insult, it may add to damage through oxidative stress. Objectives This study investigated the cardioprotective effects of a single intravenous dose of heat shock protein-72 (HSP72) coupled to a single-chain variable fragment (Fv) of monoclonal antibody 3E10 (3E10Fv) in a rabbit ischemia-reperfusion model. The Fv facilitates rapid transport of HSP72 into cells, even with intact membranes. Methods A left coronary artery occlusion (40 min) reperfusion (3 h) model was used in 31 rabbits. Of these, 12 rabbits received the fusion protein (Fv-HSP72) intravenously. The remaining 19 control rabbits received a molar equivalent of 3E10Fv alone (n = 6), HSP72 alone (n = 6), or phosphate-buffered saline (n = 7). Serial echocardiographic examinations were performed to assess left ventricular function before and after reperfusion. Micro–single-photon emission computed tomography imaging of 99mTc-labeled annexin-V was performed with micro–computed tomography scanning to characterize apoptotic damage in vivo, followed by gamma counting of the excised myocardial specimens to quantify cell death. Histopathological characterization of the myocardial tissue and sequential cardiac troponin I measurements were also undertaken. Results Myocardial annexin-V uptake was 43% lower in the area at risk (p = 0.0003) in Fv-HSP72–treated rabbits compared with control animals receiving HSP72 or 3E10Fv alone. During reperfusion, troponin I release was 42% lower and the echocardiographic left ventricular ejection fraction 27% higher in the Fv-HSP72–treated group compared with control animals. Histopathological analyses confirmed penetration of 3E10Fv-containing molecules into cardiomyocytes in vivo, and treatment with Fv-HSP72 showed fewer apoptotic nuclei compared with control rabbits. Conclusions Single-dose administration of Fv-HSP72 fusion protein at the time of reperfusion reduced myocardial apoptosis by almost one-half and improved left ventricular functional recovery after myocardial ischemia-reperfusion injury in rabbits. It might have potential to serve as an adjunct to early reperfusion in the management of myocardial infarction.

Background and Purpose— This study investigated the effects of intravenous recombinant Fv-Hsp70 protein on infarction volume and behavior after experimental ischemic stroke. Methods— Focal cerebral ischemia was produced by occluding the middle cerebral artery using the intraluminal suture technique. Rats subjected to 2 hours of focal ischemia were allowed to survive 24 hours. At 2¼ hours and 3 hours after onset of ischemia, Fv-Hsp70 recombinant protein (0.5 mg/kg) or saline was injected through the tail vein. Sensorimotor function and infarction volume were assessed at 24 hours after ischemia. Results— Administration of Fv-Hsp70 after focal cerebral ischemia significantly decreased infarct volume by 68% and significantly improved sensorimotor function compared with the saline-treated control group. Western blots showed Fv-Hsp70 in ischemic but not in control brain; and Fv-Hsp70 suppressed endogenous Hsp70. Conclusion— Fv-Hsp70 protected the ischemic brain in this experimental stroke model.

Fluorescence characteristics of Yb 3+ :Ce 3+ :Er 3+ -codoped fluoride glasses is reported. Yb 3+ codoping improved the excitation efficiency at 980 nm pumping and Ce 3+ codoping improved the branching ratio of the Er 3+ 4 I 11/2 – 4 I 13/2 transition level, resulting in an enhancement in the fluorescence quantum yield at 1550 nm. The energy transfer dynamics of the Yb 3+ :Ce 3+ :Er 3+ -codoped fluoride glass was also analyzed based on a rate equation model. The separately measured energy transfer rates between Yb 3+ and Er 3+ , and between Er 3+ and Ce 3+ agreed to some extent with the theoretical simulation based on the rate equation model at a lower Yb 3+ concentration (

Summary Aim : To assess safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis for distal ulcerative colitis. Methods : Granulocyte and monocyte adsorptive apheresis therapy (five aphereses for 5 consecutive weeks) was performed for 30 consecutive patients with active distal ulcerative colitis. Patient compliance, adverse effects and clinical symptoms were regularly assessed. Results : Adverse effects were noted during nine (6%) apheresis sessions in eight patients; slight headache five, transient abdominal pain with tenesmus two, fever (38 °C) one and mild liver dysfunction one. None of these adverse effects was serious and all patients could complete five aphereses. Clinical symptoms (stool frequency and consistency, rectal bleeding, tenesmus and mucus in stools) significantly improved after the third apheresis. Clinical remission (normal stool frequency and no rectal bleeding) was achieved in 21 patients (70%) after five aphereses. The median Disease Activity Index score significantly decreased; from 6 [interquartile range (IQR): 4–7] to 2 (IQR: 1–3) (P

The advantages of using 1, 96, or 384 precision glass syringes in automated high-throughput microdispensers in creating highly uniform and reproducible DNA, protein, and organic compound array filters and slides are described. Using the Hydra® Microdispenser and TangoTM Liquid Handling system, 0.1–5 ng (in 50–300 nL) PCR-amplified, human cancer-related genes and housekeeping genes were spotted onto nylon membranes and coated slides. Protein solutions of 50μg/mL to 1 mg/mL were spotted onto coated slides or onto MaxiSorpTM 96-well plates. Up to 6144 spots/membrane and up to 1000 spots/slide were printed. The size of the spots created by glass syringes was uniform and reproducible (precision variation of less than 5%) from spot to spot and membrane to membrane. Using a Tango 384 system, a total of ten 6144-spot filters can be produced in approximately 25 min, translating into a spotting speed of 2.5 min/membrane.

Defect centers in annealed p-GaSe have been studied by using photoluminescence (PL), optical absorption, and X-ray diffractometer measurements. A broad emission band at 1.45 eV (at 77 K) is observed in the PL spectra of the annealed samples. From the temperature dependences of the PL intensity, peak energy, and full width at half-maximum, the 1.45 eV band shows the characterization of the recombination mechanism in the configurational coordinate model. The acceptor level at about 0.45 eV above the valence band is detected in the annealed samples by using optical absorption measurements and is associated with dislocations or stacking faults. Moreover, the results of X-ray diffraction measurements indicate that the density of Se atoms in the interlayer and of Se vacancies is increased in the annealing process. In addition to the results of the X-ray diffraction measurements, it is found that the emission band at 1.45 eV is related to the Se vacancy-acceptor complex.

This paper describes an experimental investigation of the coagulation of particles in oil under the action of an a.c. electric field. The investigation is carried out to acquire fundamental data to develop an electrostatic liquid filter with higher performance. The coagulation process of spherical silica particles in oil is observed by tracking a certain particle arbitrarily chosen and using a video-microscope with a charge coupled device (CCD) camera under various mechanical conditions. The observations show that particles are coagulated by approaching one another, in particular, owing to the velocity gradient of flow and entering the region where attractive forces are exerted among them, and that the velocity gradient in the direction of the electric field is more effective for particles to be coagulated than that in the direction perpendicular to the electric field. The experiment shows that a certain frequency of the a.c. electric field at which the coagulation is most promoted exists, and that the frequency increases with increase in the strength of the a.c. electric field and the zeta potential of particles. The experimental results suggest that the mean amplitude of oscillation of particles in the direction of the a.c. electric field may dominate the degree of coagulation.

Background and Purpose —The mechanisms of excitotoxic cell death in cerebral ischemia are poorly understood. In addition to necrosis, apoptotic cell death may occur. The purpose of this study was to determine whether an established model of cerebral hypoxia-ischemia in the neonatal rat demonstrates any features of apoptosis. Methods —Seven-day-old neonatal rats underwent bilateral, permanent carotid ligation followed by 1 hour of hypoxia, and their brains were examined 1, 3, and 4 days after hypoxia-ischemia. The severity of ischemic damage was assessed in the dentate gyrus and frontotemporal cortex by light microscopy. Immunocytochemistry was performed to detect the cleavage of actin by caspases, a family of enzymes activated in apoptosis. Terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling (TUNEL) reactivity was examined in the cortical infarction bed and dentate gyrus. Neonatal rat brain DNA was run on agarose gel electrophoresis to detect DNA fragmentation. Ethidium bromide–staining and electron microscopy were used to determine whether apoptotic bodies, 1 of the hallmarks of apoptosis, were present. Results —The frontotemporal cortex displayed evidence of infarction, and in most rats the dentate gyrus showed selective, delayed neuronal death. Immunocytochemistry demonstrated caspase-related cleavage of actin. TUNEL and DNA electrophoresis provided evidence of DNA fragmentation. Ethidium bromide–staining and electron microscopy confirmed the presence of chromatin condensation and apoptotic bodies. Conclusions —Features of apoptosis are present in the described model of cerebral hypoxia-ischemia. Apoptosis may represent a mode of ischemic cell death that could be the target of novel treatments that could potentially expand the therapeutic window for stroke.

Summary The authors performed Hallux valgus operations on ten patients in 20 feet using Ilizarov external fixator, which is a useful apparatus for treating severe foot deformities. This fixator consists of a half-ring which is made of carbon, six male or female posts, six wire-fixing bolts, and three olive wires 1.5 mm in diameter. The total weight of the instrument is only about 200 g. Instrument fixation lasted around 5–6 weeks. The method of osteotomy comprised 20 distal soft tissue procedures, and the basal metatarsal osteotomy was fixed by two Kirschner (K)-wires 1.8 mm in diameter. The deformity of the Hallux valgus was successfully corrected in all 20 feet. The authors found that all patients were able to walk without crutches immediately after the operation, and the forefoot transverse arch was reconstructed.

A spectrally narrowed widely tunable Ce/sup 3+/: Er/sup 3+/-codoped fluorozirconate (ZBLAN) fiber laser with a continuous-wave laser diode pumping at 975-nm pumping is demonstrated. Wide tunable range over 120 nm (1490-1610 nm) is attained by using a diffraction grating combined with a tuning mirror in the Ce/sup 3+/: Er/sup 3+/-ZBLAN fiber laser cavity. Rate-equation model analysis shows that the tunable range can expand further by using a wavelength-dependent reflectivity cavity mirror.

A positron lifetime study has been done on dielectric multilayer cavity mirrors for free-electron-laser experiments by the use of a variable-energy pulsed positron beam. A long-lived ortho-positronium component has been observed at low positron energy region, corresponding to the depth of the top amorphous SiO2 layer. The intensity of the positronium component correlates with the degradation and restoration of the mirrors. We discuss the relation between the positronium intensity and degradation mechanism of the mirrors. The present studies revealed that the slow positron lifetime technique is highly sensitive to the properties of the mirrors and is useful for the evaluation of the mirrors.

A high speed half-tracked truck using a new type of metal-coreless rubber track for traveling and load-carrying both on- and off-road was developed. In this application a conventional embedded-metal rubber track was examined in a first step, and was found to be unsuitable because of its chain-type structure. Then a new type of positive drive metal-coreless rubber track with endless spiral cable reinforcement was developed to meet all of the desired performance, i.e. low driving resistance, low heat build-up due to flexing, low noise, low vibration, light weight, good flexibility, low wear, etc. The development of this track, along with the use of properly matched undercarriage and suspension, has renewed interest in the use of half-tracked trucks. This truck is based on a conventional four-wheel-drive dump truck of two tonnes payload with its rear wheels converted into rubber tracks. Both high mobility off-road and traveling speed faster than 60 km/h on-road are obtained without detracking of the rubber tracks from the undercarriage. Therefore, the truck is capable of transporting its load between on- and off-road without transshipment. An identical driver's license for the same category as the original truck has been granted by the Japanese Ministry of Transportation since 1992. In this paper, the structure of the truck, the metal-coreless rubber track developed especially for high-speed traveling, the test results, and some market applications are reported.

After 18 years of operation and production of 48.2 Mt, the No. 6 Chiba blast furnace is a key equipment for production of pig iron and production of energy. The operating procedures elaborated during these years and a complement of monitoring of the lining wear allow to forecast an operation until the relining scheduled in 1998.

Rheumatoid arthritis (RA) is a destructive polyarthritis in which synovial-like fibroblasts (SFs) invade and erode cartilage by expressing membrane-anchored type 1 matrix metalloproteinase (MT1-MMP). The mitogen activated protein kinase (MAPK) pathway is activated in RA SFs, but the mechanism of activation is unknown. Here we identify aberrant BRAF splice variants with deletions in both the kinase domain and RAS-binding domain (RBD) in SFs from the majority of RA patients and show that these BRAF splice variants constitutively activate MAPK through CRAF, increase expression of MT1-MMP, and enhance fibroblast invasion of collagen.

We demonstrate the low-noise and high-gain operation of a fluoride Er/sup 3+/ and Ce/sup 3+/ codoped fiber (F-ECDF) amplifier with 980-nm pumping. A 980-nm-pumped F-ECDF with a length of only 45 cm exhibits a noise figure of 20 dB with a gain ripple of

Fiber laser operating property at 1.55-/spl mu/m band in a newly developed Ce,Er:ZBLAN fiber by a continuous-wave laser diode pumping at 980 nm is presented. The output characteristics of the Ce,Er:ZBLAN fiber laser system are analyzed in detail based on the rate equations model by taking into account the energy transfer between Ce/sup 3+/ and Er/sup 3+/ ions, as well as the upconversion mechanisms. The promotion role of the Ce in the erbium-doped ZBLAN for the 1.55-/spl mu/m band fiber laser operation has been realized.

Various components in the 40 tpd fluidized-bed IGCC gasifier were inspected at the site and some of them were analysed destructively in the laboratory to reveal the damage accumulated on the components and to verify the reliability of the materials used.

Novel extremely small multi-fiber connectors for optical interconnection systems are designed, fabricated, and evaluated. It has low insertion loss and excellent environmental endurance. It meets the requirement of higher integration in optical backplane systems.

To evaluate the clinical efficacy of monoclonal antibody (mAb) 3E10 Fv antibody-mediated p53 protein therapy, an Fv-p53 fusion protein produced in Pichia pastoris was tested on CT26.CL25 colon cancer cells in vitro and in vivo in a mouse model of colon cancer metastasis to the liver. In vitro experiments showed killing of CT26.CL25 cells by Fv-p53 but not Fv or p53 alone, and immunohistochemical staining confirmed that Fv was required for transport of p53 into cells. Prevention of liver metastasis in vivo was tested by splenic injection of 100 nmol/L Fv-p53 10 min and 1 week after injection of CT26.CL25 cancer cells into the portal vein of BALB/c mice. Mice were sacrificed 1 week after the second injection of Fv-p53 and assigned a quantitative metastasis score. Control mice had an average metastasis score of 3.3 ± 1.3, whereas mice treated with Fv-p53 had an average metastasis score of 0.8 ± 0.4 (P = 0.004). These results indicate that Fv-p53 treatment had a profound effect on liver metastasis and represent the first demonstration of effective full-length p53 protein therapy in vivo. mAb 3E10 Fv has significant clinical potential as a mediator of intracellular and intranuclear delivery of p53 for prevention and treatment of cancer metastasis. [Cancer Res 2007;67(4):1769–74]

Wide tuning over 120 nm and passive mode locking of a Ce/sup 3+/-Er/sup 3+/-ZBLAN fiber laser by a semiconductor saturable-absorber is described for the first time. A Q-switched mode-locked output was obtained with 400 MHz repetition rate.

A 2/spl times/40W (into 4/spl Omega/ with a 20V supply) integrated stereo /spl Delta//spl Sigma/ class D amplifier with 100dB SNR is realized in a 0.6 /spl mu/m CMOS process with DMOS transistors and buried Zener diodes. Feedback from power stage outputs gives 0.001% THD and 65dB PSRR. The modulator clock rate is 6MHz, but dynamically adjusted quantizer hysteresis reduces the output data rate to 450kHz, helping achieve 88% efficiency.

FcgammaRIII (CD16) is found in two alternative forms, a transmembrane FcgammaRIIIa expressed on NK cells and macrophages, and a glycosylphosphatidylinositol-linked FcgammaRIIIb present on neutrophils. Previously, we measured soluble FcgammaRIIIa (sFcgammaRIIIa) in plasma of NA(1 +, 2-) phenotyped donors with the anti-FcgammaRIII monoclonal antibody (MoAb) GRM1, which recognizes NA2-FcgammaRIIIb and FcgammaRIIIa. The level of sFcgammaRIIIa, as well as the total sFcgammaRIII (sFcgammaRIIIa plus sFcgammaRIIIb) in patients with rheumatoid arthritis (RA) was significantly higher than that in healthy controls. In this study, we measured sFcgammaRIIIa(M)(phi) in plasma with a newly developed anti-FcgammaRIII MoAb, MKGR14 (mIgM), which recognizes FcgammaRIIIa(M)(phi) specifically. From the recovery of purified sFcgammaRIIIa(M)(phi), the amount of sFcgammaRIIIa(M)(phi) present was about half that of sFcgammaRIIIa(NK), and that of sFcgammaRIIIa was about 50 times lower than that of sFcgammaRIIIb in pooled plasma from healthy NA(1 +, 2-) phenotyped donors. The level of sFcgammaRIIIa(M)(phi) in RA patients was about four times higher than that in healthy controls. In RA patients, both the sFcgammaRIIIa(M)(phi) and sFcgammaRIIIa levels were increased as proportionally as the Lansbury Index. The sFcgammaRIIIa, but not sFcgammaRIIIa(M)(phi) levels, were increased directly proportional to C-reactive protein. sFcgammaRIIIa(M)(phi) may be a novel marker of disease activity in RA.

In office buildings, the requirement is that the room air-conditioning control system has to provide comfortable thermal feeling for the working people. While energy saving may sometimes conflict with comfort, it is possible to eliminate the wasteful use of energy associated with its overuse without prejudicing the comfort. The basic concept is that the target set values for the room temperature should be changed dynamically so as to suit the constantly changing room environment. The paper shows that the well-known comfort index PMV is useful for air-conditioning control systems aimed at both energy-saving and comfort.

Input power dynamic range (IPDR) of an optical 3R regenerator with double-stage SOA-based polarization discriminated switch was experimentally investigated at 40 Gbit/s. The relation between IPDR characteristic and pattern effect was discussed.

We need uniform heating in microwave ovens. To remove unevenness, it is important to analyze the electromagnetic field distribution in the cavity of microwave ovens, and to optimize it. Generally, we must use three-dimensional analysis and are often faced with the problem of exceeding the computer resources available. We adopt the FD-TD method, which has the advantage of using computer memory more efficiently than other space dividing methods, such as FEM. But the FD-TD method is mainly used for transient analysis, and not often for steady state analysis. We first investigate the steady state convergence and then compare the calculated electromagnetic energy distribution with experimental heating unevenness. We see that the results are fairly similar.

The small objects which are far less than the focused beam diameter were imaged with a C-scan acoustic microscope, and the acoustic image sizes were compared with the actual sizes. The sizes of flat strips of width over 0.01 mm and steel wires of diameter over 0.02 mm were estimated within 30% error by using the reflection ratio, which is the ratio of the intensity of reflection signal from an object to that from a reference plane. The validity of this method is also shown for small spherical voids within ceramics.

Fiber laser operation at 1.55 /spl mu/m band was first time realized in a Ce/sup 3+/:Er/sup 3+/:ZBLAN multimode fiber by cw LD pumping at 980 nm. The performance of wavelength tunable fluoride fiber laser around 1.55 /spl mu/m has been achieved.

A 533 MHz 2.5 W 2132 MIPS 12.8 GOPS 2.1 GFLOPS 8-way VLIW embedded multimedia processor occupies a 7.8/spl times/7.8 mm/sup 2/ die in a 7-layer metal 0.11 /spl mu/m CMOS at 1.2 V. VLIW, SIMD, dynamic branch prediction, non-aligned dual load/store mechanism and a crosstalk-aware design flow contribute to performance.

Publisher Summary Boundary integral equation approach is investigated for solving inverse problems related to ultrasonic nondestructive determination of defects in structures for some time. The setting of these elastodynamic inverse problems assumes that one knows both incident waves to illuminate the defects, and the scattered waves from the defects. However, neither of these waves are easily measured in experiments using ultrasonic transducers, mainly because the output of ultrasonic transducers has not been related to physical quantities in a quantitative manner. In view of this, this chapter considers an inverse problem that uses real data obtained with a laser interferometer to determine the waves from the transducer. This chapter deals with the description of the experiment carried out for the present analysis. The specimen used in this experiment has a circular cylindrical hole as an artificial defect. This specimen is designed so that one may obtain data to determine the elastic wave from the transducer, and measure the scattered wave from the defect at the same time. After a brief recapitulation of the inverse problem of determining the elastic wave from the transducer, there is a brief discussion on BIE analysis for estimating the scattered wave from the defect.

Purpose To test the clinical efficacy of antibody-mediated protein transduction of p53 into cancer cells in vivo in a mouse model of colon cancer metastasis to liver. Methods An Fv fragment of mAb 3E10 was previously shown to penetrate into cancer cells and localize in the nucleus. A His6-tagged Fv-p53 fusion protein was produced in Pichia pastoris X-33 yeast cells transfected with pPICZA-Fv-p53. Fv-p53 was isolated on NiNTA-agarose and assayed for killing CT26.CL25 colon cancer cells in vitro and CT26.CL25 cells injected into the portal vein of syngeneic Balb/c mice. Results Experiments in vitro demonstrated killing of CT26.CL25 cells by Fv-p53 but not Fv or p53 alone, and immunohistochemical staining confirmed that Fv was required for transport of p53 into cells. Prevention of liver metastasis in vivo was tested by portal vein injections of 100 nM Fv-p53 10 minutes and 1 week after injection of cancer cells. Mice were sacrificed 2 weeks after the second injection of Fv-p53 and assigned metastasis scores based on the following criteria: 0 - no liver metastasis; 1 - minimal infiltration (less than 1 cm2 area of metastasis); 2 - mild to moderate infiltration (1-2 cm2 area of metastasis); 3 - severe infiltration (greater than 2 cm2 area of metastasis but the liver was not entirely infiltrated); 4 - complete infiltration. As shown in Table 1, Fv-p53 prevented liver metastasis. Conclusion Fv-p53 treatment had a profound impact on liver metastasis. These results demonstrate the clinical potential of an antibody Fv fragment as a protein transduction domain for intracellular/intranuclear delivery of p53 for prevention of cancer metastasis in vivo.

A great deal of interest has been directed to the pathogenesis of brain injury after stroke in human disease. In the United States approximately 175,000 fatalities and many more disabled are directly attributed to stroke every year (Adams and Victor, 1993). Many metabolic and biochemical processes occur during and after the cessation of blood flow to specific areas of the brain which might directly affect the clinical outcome. In recent years studies in animal models have identified and described the heat shock or stress response in hypoxic-ischemic brain. This chapter summarizes the main findings of the stress response and HSP 70 in the brain after hypoxia-ischemia and then correlates those findings with work performed in cell culture models. Included is a discussion of the regulation of HSP 70, associated signal transduction pathways, cellular proteins and metabolites. Finally a brief discussion of future directions using new experimental models of stress proteins is presented.