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Eser, Sultan (Balikesir Author), Background In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. Methods CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights.Findings For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). Interpretation The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer., American Cancer Society Centers for Disease Control and Prevention Swiss Re Swiss Cancer Research foundation Swiss Cancer League Institut National du Cancer La Ligue Contre le Cancer Rossy Family Foundation US National Cancer Institute Susan G Komen Foundation

At a high-power proton synchrotron, betatron tune shifts induced by space charge effects cause beam loss which limits the beam intensity. To achieve further high beam intensity at the main ring of the Japan Proton Accelerator Research Complex, precise control of the tune shift is indispensable. When carrying out multi-bunch measurements, we observed that the dependence of the tune shift intensity on the number of bunches follow opposite slope trends for the horizontal and vertical directions. The influence of the bunch spacing was also observed. We report on a simplified tune shift model reconstruction for understanding the origin of these phenomena and present a correction of the tune shifts for reducing beam loss up to 30 %., Proceedings of the 10th Int. Particle Accelerator Conf., IPAC2019, Melbourne, Australia

Unexpected positive results from the widely used IDEXX ELISA for the detection of antibodies to porcine reproductive and respiratory syndrome virus (PRRSV) may confound investigations of the disease. Supplementing the ELISA with blocking agents and the use of IgG purified from serum samples had no effect on the unexpected positive results, suggesting that they were due to an antibody-antigen reaction. Simple competitive and blocking ELISAs were developed by modifying the IDEXX ELISA, and they and an indirect fluorescent antibody test (IFAT) were used to examine PRRSV antibodies in 33 antibody-negative, 88 antibody-positive and 73 unexpectedly positive sera. All the unexpectedly positive sera were negative by IFAT, and 89.0 per cent were negative by both the competitive and blocking ELISAs. The competitive ELISA (97.7 per cent) and the blocking ELISA (96.5 per cent) detected more positive sera than the IFAT (90.9 per cent). These results show that both ELISAs are capable of distinguishing positive and unexpectedly positive sera, and suggest that most of the unexpected positive signals are false-positives.

One disincentive to the encapsulation of semiconductor devices using transfer molding is the resulting deterioration in releasability. This is because deterioration in releasability causes the chip to crack and external appearance defects to be transcribed from the mold stain. In this study, the authors have measured the in situ release force using an actual semiconductor package (LQFP2020), and have investigated the release behavior by numerically simulating the release process. The release force was found to be about 5 to 8 N, and the release time was 30 ms or less after continuous molding of 300 shots. The relationship between various release factors and the release force was also investigated. With regard to the surface roughness of the mold cavity, the release force of a ldquosatin-finished surfacerdquo was about half of that of a ldquomirror surface.rdquo In addition, the release force was slightly reduced by reducing the cure time and the release speed.

Nonsuppurative encephalitis was experimentally induced in 3-week-old piglets by a single intravenous inoculation of either of two strains (IB 2001 or AS-6) of Japanese encephalitis flavivirus (JEV) isolated from field pigs. The lesions, which consisted of neuronal necrosis, neuronophagia, glial nodules, and perivascular cuffing, were distributed in the cerebrum, midbrain, pons, medulla oblongata, and cerebellum, particularly in the gray matter of the frontal and temporal lobes and thalamus. The gray matter of the spinal cord of piglets that were given the AS-6 strain also was affected. JEV antigen was immunohistochemically detected in the cytoplasm of the nerve cells in the cortex of the frontal and temporal lobes and in the gray matter of the thalamus and midbrain. Two JEV strains isolated from field pigs exhibited neurovirulence, inducing nonsuppurative encephalitis in piglets.

Objective To compare the ratio of free prostate specific antigen (fPSA), total PSA (tPSA) and complexed PSA (cPSA, measured using a novel immunoassay) with other variables used to detect prostate cancer in patients with intermediate serum PSA levels of 4.1–10.0 ng/mL. Patients and methods From July 1997 to August 1998, 140 consecutive patients were assessed; all had intermediate serum PSA levels and/or abnormal findings on a digital rectal examination. All patients underwent transrectal ultrasonography (TRUS)-guided biopsy, and the prostate and transition zone volumes were determined by TRUS. Free and tPSA were measured using the Tandem-R assay (Hybritech Corp., San Diego, CA). PSA complexed with α1-antichymotrypsin (cPSA) was measured using an appropriate assay. The ability of cPSA, free-to-total PSA ratio (f/tPSA), free-to-complexed PSA ratio (f/cPSA), tPSA density of the whole prostate (PSAD), of the transition zone (tPSATZ), and cPSA density of the whole prostate (cPSAD) and of the transition zone (cPSATZ) to improve the power of PSA in detecting prostate cancer was evaluated using receiver operating characteristic (ROC) curves. Results Of the 140 patients, 126 had histologically confirmed benign disease and 14 had prostate cancer. The cPSA alone had better specificity for detecting prostate cancer than had tPSA alone but the difference was not significant. The area under the ROC curve for f/cPSA was larger than those for all other variables. With a 93% sensitivity for detecting prostate cancer, a f/cPSA threshold of 25% would result in fewer unnecessary biopsies (40% f/cPSA specificity) than with all other PSA variables. The difference in the resolution was significant between f/cPSA and tPSA, cPSA, tPSAD and tPSATZ, but not with f/tPSA, cPSAD or cPSATZ. In patients with a prostate volume of

A coronary stent was made radioactive by implantation of 133Xe ions for the purpose of suppressing the re-narrowing of the part of blood vessel in which the stent is implanted. Electrons of relatively low energies emitted in the decay of 133Xe may give an antiproliferative effect of ionizing radiation to the intimal cells within a limited range of 1 mm. A 133Xe+ beam accelerated at 40 or 60 keV was directed to several stainless steel stents mounted on a target-holder table that could revolve and move up and down to distribute the 133Xe+ ions within a stent as well as among the stents. The radioactive stents produced contained up to 100 kBq of 133Xe and were implanted into the abdominal aortas of rabbits. Neointimal thickening was analyzed by histomorphometry for samples taken 4 weeks after stent implantation. The results indicate that the radioactive stents have a potential to suppress neointimal hyperplasia in rabbits.

The metabolism of 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate (bishomoCDC-sul), the sulfonate analogue of bishomochenodeoxycholic acid, and its effect on biliary bile acid composition were studied during chronic administration in the hamster. After oral administration of radiolabeled bishomoCDC-sul, more than 80% of the radioactivity was excreted into the feces within 7 days, both as the unchanged sulfonate (38.5%) and two more polar metabolites (50.0% and 11.5%). The half time of the fecal excretion was 1.6 days. In gallbladder bile, the unchanged sulfonate and its major metabolite accounted for 19.1% and 19.8% of total bile acids, respectively. In another experiment, hamsters were fed bishomoCDC-sul with antibiotics to evaluate the site of biotransformation. Even when the number of intestinal microorganisms was greatly reduced, the same three metabolites were found in the feces: bishomoCDC-sul (44.0%) and the two polar metabolites (30.8% and 25.1%). The major metabolite was isolated from feces of the hamsters fed bishomoCDC-sul without antibiotics. Its chemical structure was identified by mass spectrometry and nuclear magnetic resonance spectroscopy as the 15 alpha-hydroxylated derivative, namely sodium 3 alpha,7 alpha,15 alpha-trihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate. These results indicate that after oral administration, the sulfonate analogue of bishomochenodeoxycholic acid underwent enterohepatic circulation like a natural bile acid and was transformed, in part, into the 15 alpha-hydroxylated derivative and another more polar metabolite in the liver of hamsters. There was no evidence that bishomoCDC-sul was dehydroxylated to a lithocholic acid analogue during enterohepatic cycling.

MR images of the neck were prospectively studied in 19 patients with hyperparathyroidism. Fast low angle shot (FLASH) sequence was performed in addition to T1- and T2-weighted spin echo (SE) sequences. FLASH images were obtained with 320/12/20° (TR/TE/flip angle) using presaturation technique. TE of 12 ms was chosen to eliminate high signal of fat tissue. In the evaluation of detectability, a combination of T1-weighted SE and FLASH images (T1WI + FLASH) was compared with a combination of T1- and T2-weighted SE images (T1WI + T2WI). MR imaging correctly depicted 20 of 30 abnormal glands on both T1WI + FLASH and T1WI + T2WI. FLASH imaging effectively eliminated high signal of fat tissue. Nineteen abnormal glands demonstrated higher signal than surrounding tissues on FLASH images, whereas 12 glands were high-intense on T2-weighted SE images. We conclude that FLASH imaging provides improved tissue contrast and anatomic delineation and, thus, may replace T2-weighted SE imaging in the neck.

In NGF-treated PC12 cells, nicotine-induced K+ release was measured with a K(+)-sensitive microelectrode. The K+ outflow via nicotinic ACh receptor cation channels was inhibited by various psychotomimetic sigma ligands in the sequence of PCP, dextromethorphan >> DTG, MK 801, (+)SKF10047 >> (+)3-PPP. The K+ release was not affected by the neuroleptic sigma ligand haloperidol nor by the calcium antagonist nifedipine. The results suggest that psychotomimetic sigma ligands inhibit nicotine-stimulated K+ flux by interacting with nicotinic, rather than via sigma 2 receptors.

The 3-GeV rapid cycling synchrotron (RCS) of the Japan Proton Accelerator Research Complex (J-PARC) was commissioned in October 2007, and successfully accomplished 3 GeV acceleration on October 31. Six run cycles through February 2008 were dedicated to commissioning the RCS, for which the initial machine parameter tuning and various underlying beam studies were completed. Then since May 2008 the RCS beam has been delivered to the downstream facilities for their beam commissioning. In this paper we describe beam tuning and study results following our beam commissioning scenario and a beam performance and operational experience obtained in the first commissioning phase through June 2008.

Ictogenesis and epileptogenesis during development are key phenomena in the establishment of epilepsy. In exploring these processes, we will clarify not only the mechanisms of abnormalities for the neuronal network, but also the physiology of higher brain functions such as learning and memory. Since epilepsy is defined as the repeated synchronous hyperactivity of cortical neurons, it is also important to view epileptic phenomena according to ‘states’ – i.e., transition from the preictal to the ictal state and from the interictal to the ictal state. In this context, when we discuss ‘repeated’ hyperactivity, we generally refer to transitions from the interictal to the ictal state, and when we investigate ‘the first synchronous’ discharge, we generally refer to transition from the preictal to the ictal state. During epileptogenesis, a large number of genes are expressed, and this expression is dependent on the development state of the animal as well as the epileptic ‘state.’ Among the genes that are highly expressed are those responsible for free-radical production and synaptic reorganization, inducible nitric oxide synthetase (i-NOS), constitutive neural NOS (n-NOS), epitherial NOS (e-NOS), apoptosis regulation (Bcl-2, Bcl-XL, Bax), neurotrophic factors (brain-derived nerve growth factor (BDNF), fibloblast growing factor-2 (FGF-2), neurotrophin-3 (NT-3)), cell-cycle reentry (cycalin A, B, D, E, cyclin-dependent kinase-1,-2,-4 (CDK-1, -2, -4)), and inflammatory signal transduction (IL-1a, IL-1b, tumor necrotizing factor-a (TNF-a), interleukin 1 receptor (IL-1r), interleukin 1 receptor antagonist (IL-1ra)). The EL mouse is an animal model of secondary generalized seizure. Seizure threshold in this animal depends on its developmental state and its seizure history. Thus, the EL mouse is a particularly useful animal model to investigate the role or significance of seizure-related expression of different genes.

Nonsuppurative encephalomyelitis with neurological signs expressed as flaccid paralysis of the hindlimbs was experimentally induced in three-week-old piglets by a single intravenous injection of the Toyama 2002 strain of porcine teschovirus (PTV) isolated from field pigs in Japan. Lesions characterized by perivascular cuffing of mononuclear cells, focal gliosis, neuronal necrosis and neuronophagia were observed, mainly in the ventral horn of the spinal cord. Nonsuppurative ganglionitis of the spinal ganglion and neuritis of the spinal root were also detected. PTV antigens were detected immunohistochemically and the distribution of these antigens corresponded closely with the distribution of brain lesions. PTV antigens were observed in the ganglion cells before the appearance of the inflammatory changes 3 days post-inoculation (dpi) and were present in the dorsal root and spinal cord on 9 dpi. No lesions of the central nervous system were induced in pigs by oral or intranasal inoculation of this strain of PTV.

Non-suppurative encephalitis was experimentally induced in three-week-old piglets by a single intranasal inoculation of Japanese encephalitis virus (JEV) isolated from field pigs. The lesions consisted of glial cell aggregates and perivascular cuffing throughout the olfactory tract and pyriform cortex. JEV antigens were detected in the cytoplasm and neuronal processes of small nerve cells in the granule cell layer of the olfactory bulb, in the neuronal processes of the olfactory tract and in the cytoplasm of neurons in the pyriform cortex. The distribution of the antigens corresponded closely with the distribution of brain lesions. These findings suggest that JEV may enter the brain by the olfactory pathway in addition to via haematogenous spread in piglets.

Pattern electroretinograms were recorded to checkerboard stimuli of various check size to both onset-offset pattern and pattern reversal under most similar conditions of contrast and luminance. With onset-offset pattern the amplitude of the p-q and q-r components of the onset response showed a peak for checks of about 20 min of arc (spatial tuning), whereas the offset response was spatially nonselective at high contrast regardless of the luminance level. With pattern reversal the potentials were similar to those after algebraic summation of onset and offset responses both in waveform and check size of peak amplitude at 50 min of arc. From this we conclude that summation of contrast (onset) and luminance (offset) components is responsible for the shift from 20 min of arc (onset tuning) to 50 min of arc (reversal tuning). The study recommends the application of pattern stimuli in an onset-offset mode for studying antagonistic receptive field properties in the human electroretinogram.

J-PARC has three accelerators running at the different repetition rates; a 400-MeV linac (50Hz), a 3-GeV rapid cycling synchrotron (RCS, 25Hz), and a 50-GeV synchrotron (MR). The linac and the RCS deliver the beam pluses to the different destinations in each cycle. The destinations are scheduled according to the machine operations. We define two kinds of timing, "scheduled timing" and "synchronization timing" so that the accelerators are operated with proper timing and the beam pulses are transported to the experimental facilities or the next accelerators. The J-PARC complex requires a stable and precise timing system. The system is based on a master clock generated by a synthesizer and the triggers are operated independently of the AC-line frequency. We describe the design of the J-PARC timing system and their configuration, and also present the hardware details.

Porcine reproductive and respiratory syndrome virus (PRRSV) has two genotypes, the North American-type (NA-type) and the European-type (EU-type), and each genotype is also genetically diverged. We sequenced the ORF5 gene of 30 PRRSVs isolated from 23 prefectures of Japan during 1992 and 1993 and during 2000 and 2001. All of the isolates were of the NA-type. Phylogenetic analysis of the overall NA-type viruses isolated from around the world identified five major genetic clusters. The 1992-1993 Japanese samples belonged to only two genetic clusters, while the 2000-2001 samples included more diverged ORF5 genomes. One genetic cluster, which included 63% (20/32) of Japanese isolates, one Taiwanese isolate and one Chinese isolate, was mainly found in the eastern part of Japan. Another genetic cluster, which was found in various areas around the world, was distributed in the western part of Japan.

A direct fast‐chopped beam extracted from a surface‐plasma H− ion source is proposed and a preliminary test has been examined. The converter bias voltage is modulated by rf pulses and the extracted H− beam is observed. The direct fast‐chopped H− beam extracted from the ion source has a good response to the modulation of the converter bias voltage, as expected. The chopped H− beam extracted by this method has been injected into the 500 MeV booster synchrotron at KEK‐PS.

A location detector with a fiber-optic gyroscope (FOG) and its application to a patrol car location system are described. Several methods of handling the output signal of the FOG as well as other kinds of techniques have been developed. These technologies are also applied to navigation systems used in consumer passenger vehicles. It is believed that an advanced police information system could be constructed by integrating this system with other systems. >

An antiproton accumulation and deceleration ring in the KEK proton synchrotron (KEK PS) complex has been designed. The KEK PS top energy is 12 GeV and it is enough to produce 2 GeV/c antiprotons. As many as 10/sup 5/ of them would be collected each synchrotron cycle, that is 2 second. After stacking and stochastic cooling of the beams, 10/sup 7/ to 10/sup 8/ antiprotons per hour should be available for physics experiments. There are several R&D items such as compression of the nine bunch train in the PS. Preliminary simulation has been done to look at single turn transfer of antiprotons to the proposed ring whose circumference is 1/3 of the PS.

A control system is described for automated steering systems to prevent traffic accidents. A model of the system is built by integrating a lane model and a vehicle model based on the visual servoing approach. The system is controlled by a guidance controller and an angle controller. The former is designed on the basis of steering actuator dynamics and uncertainties of vehicle parameters, and the latter is designed on the basis of steering wheel dynamics using /spl mu/ synthesis. It is proved that the proposed control system achieves vehicle stability for steering maneuvers such as obstacle avoidance.

We present a case of familial juvenile gouty nephropathy which was associated with a right renal tumor that was found incidentally. The patient was a 27-year-old woman who initially presented with acute gouty arthritis at the age of twenty years. Her mother and her sister had been attacked with acute gouty arthritis in their early twenties. Progressive deterioration in the renal function was noted in the three family members who had experienced gouty attack. Her mother was maintained on hemodialysis. As image diagnoses could not rule out malignancy in her right renal tumor, in situ non-ischemic enucleation of the right renal tumor using a microwave tissue coagulator(Microtaze) and a renal biopsy were performed. The pathological diagnosis of the renal tumor was tubulopapillary adenoma, and the renal biopsy showed minimal change in the glomeruli and tubules. The post-operative course was uneventful. The serum creatinine and creatinine clearance before and three months after the operation were 2.4 mg/dl and 2.6 mg/dl, 36.7 ml/min and 32.5 ml/min, respectively. The renal biopsy findings that glomerular and tubular changes were minimal and there was no tissue precipitation of uric acid or sodium urate, and the fact that her renal function decreased progressively despite the treatment of hyperuricemia suggested strongly that renal function might have deteriorated due to unknown factors other than hyperuricemia.

Nefiracetam, a pyrrolidone derivative developed as an anti-dementia drug, persistently potentiated currents through neuronal nicotinic acetylcholine (ACh) receptors (alpha 7, alpha 4 beta 2) expressed in Xenopus oocytes, and the potentiation was blocked by either the selective protein kinase C (PKC) inhibitors, GF109203X and staurosporine, or co-expressed active PKC inhibitor peptide. In primary cultures of rat hippocampal neurons, nefiracetam increased the rate of nicotine-sensitive miniature excitatory postsynaptic currents, without affecting the amplitude, and the increase was inhibited by GF109203X. In addition, the drug caused a marked increase in the glutamate release from electrically stimulated guinea pig hippocampal slices, and the effect was abolished by the nicotinic ACh receptor antagonists, alpha-bungarotoxin and mecamylamine. Nefiracetam induced a long-lasting facilitation of synaptic transmission in both the CAI area and the dentate gyrus of rat hippocampal slices, and the facilitation was inhibited by alpha-bungarotoxin and mecamylamine. Such facilitatory action was still found in the hippocampus with selective cholinergic denervation. The results of the present study, thus, suggest that nefiracetam enhances activity of nicotinic ACh receptors by interacting with a PKC pathway, thereby increasing glutamate release from presynaptic terminals, and then leading to a sustained facilitation of hippocampal neurotransmission. This may represent a cellular mechanism underlying the cognition-enhancing action of nefiracetam. The results also provide the possibility that nefiracetam could be developed as a promising therapeutic drug for senile dementia or Alzheimer's disease. (C) 2000 Elsevier Science B.V. All rights reserved.

The expression of Fas, a cell surface receptor directly responsible for triggering cell death by apoptosis, and its ligand (FasL) was investigated on both human colonic intraepithelial T lymphocytes (IELs) and peripheral blood mononuclear lymphocytes (PBMLs). FACS analysis indicated that IELs have increased expression of Fas compared with PBMLs, together with the progress activation marker, CD45RO. A discrete fraction of freshly isolated IELs also constitutively expressed FasL, perhaps as a result of recent in vivo activation. Using monoclonal antibody APO2.7, which detects mitochondrial 7A6 antigen specifically expressed by cells undergoing apoptosis, we further investigated the apoptosis-inducing effect of anti-Fas monoclonal antibody (CH11) on both IELs and PBMLs. FACS analysis revealed that CH11 increased the percentage of apoptotic cells, in IELs but not in PBMLs. Culture with anti-FasL monoclonal antibody (4H9) significantly recovered cell viability in IELs, but not in PBMLs. These results indicate that IELs constitutively express both Fas and FasL and that Fas crosslinking generates signals resulting in apoptosis, outlining a potential mechanism involved in intestinal tolerance.

To compare the ratio of free prostate specific antigen (fPSA), total PSA (tPSA) and complexed PSA (cPSA, measured using a novel immunoassay) with other variables used to detect prostate cancer in patients with intermediate serum PSA levels of 4.1-10.0 ng/mL.From July 1997 to August 1998, 140 consecutive patients were assessed; all had intermediate serum PSA levels and/or abnormal findings on a digital rectal examination. All patients underwent transrectal ultrasonography (TRUS)-guided biopsy, and the prostate and transition zone volumes were determined by TRUS. Free and tPSA were measured using the Tandem-R assay (Hybritech Corp., San Diego, CA). PSA complexed with alpha1-antichymotrypsin (cPSA) was measured using an appropriate assay. The ability of cPSA, free-to-total PSA ratio (f/tPSA), free-to-complexed PSA ratio (f/cPSA), tPSA density of the whole prostate (PSAD), of the transition zone (tPSATZ), and cPSA density of the whole prostate (cPSAD) and of the transition zone (cPSATZ) to improve the power of PSA in detecting prostate cancer was evaluated using receiver operating characteristic (ROC) curves. Results Of the 140 patients, 126 had histologically confirmed benign disease and 14 had prostate cancer. The cPSA alone had better specificity for detecting prostate cancer than had tPSA alone but the difference was not significant. The area under the ROC curve for f/cPSA was larger than those for all other variables. With a 93% sensitivity for detecting prostate cancer, a f/cPSA threshold of 25% would result in fewer unnecessary biopsies (40% f/cPSA specificity) than with all other PSA variables. The difference in the resolution was significant between f/cPSA and tPSA, cPSA, tPSAD and tPSATZ, but not with f/tPSA, cPSAD or cPSATZ. In patients with a prostate volume of30 mL, the cPSATZ showed better specificity for prostate cancer than tPSA alone.Measuring the level of cPSA and its derivatives may provide better differentiation of prostate cancer and benign disease than tPSA alone in patients with a tPSA level of 4.1-10.0 ng/mL.

A barrier bucket experiment with two dedicated barrier cavities was performed at the Brookhaven AGS. One of the barrier cavities was a magnetic alloy (MA)–loaded cavity and the other was a ferrite-loaded cavity. They generated a single sine wave with a peak voltage of 40 kV at a repetition rate of 351 kHz. A barrier rf system was established with these cavities and five bunches from the AGS booster were accumulated. A total of 3×10^{13} protons were stored without beam loss, and were successfully rebunched and accelerated. The longitudinal emittance growth was observed during accumulation by the barrier bucket, the blowup factor of which was about 3. The longitudinal mismatch between the rf bucket and the beam bunch was the main reason for the emittance growth. The potential distortions by beam loading of the ferrite cavity and the overshooting voltage of the MA cavity disturbed the smooth debunching.

We designed an impedance tuner consisting of an inductive material, FINEMET, to cancel the space charge impedance in the longitudinal direction. It was installed in the KEK Proton Synchrotron (PS) main ring. We observed the frequency shift of the coherent quadrupole oscillations and inferred the shift of the incoherent synchrotron oscillation. The total reactive impedance can be estimated as the coefficient between the shift and the beam intensity. The measured impedance is reduced from −j2475Ω to −j1182Ω by the impedance tuner which consists of 12 pieces of FINEMET cores. We demonstrated that the space charge impedance is compensated by the impedance tuner. This is the first time for FINEMET to be equipped with an accelerator component. One may think that the characteristics of FINEMET deteriorate under an environment with strong radiation generated by unavoidable beam loss. We have proved that the radiation dose not affect FINEMET even with a total neutron dose of 1.83×1012(n cm−2), which is considered ...

We studied the beam loading effects on the High Gradient Cavity (HGC) loaded with Magnetic Alloy (MA) by multiparticle tracking simulation. The Q-value of the cavity is variable from 0.6 to more than 10. From the view point of multi-bunch effect, it was found that either very high Q-value or low Q-value was preferable to suppress the periodic transient beam loading. The experimental results of the beam loading compensation using an electron beam are also described.

Very high field-gradient has become available by a new magnetic alloy (MA)-loaded cavity developed for high intensity proton synchrotrons. The available RF voltage per core is ten times larger than that of the ordinary ferrite core. The maximum voltage of 20 kV has been achieved by the high-field gradient cavity (HGC) of 40 cm in length. Because the intrinsic Q-value of the MA core is low, acceleration without any tuning system also becomes possible. The first beam acceleration test using the HGC has been performed successfully at the HIMAC (Heavy Ion Medical Accelerator in Chiba). Furthermore, the dual harmonic RF and barrier bucket experiments have been carried out. Another advantage of the MA-loaded cavity is that it is easy to compensate the beam loading. The feed forward beam compensation was applied for both HGC on the test bench using an electron beam and MA-loaded cavity installed in the AGS for the barrier bucket experiment. A new development for high-Q HGC using a cut core configuration will be also reported.

The first beam acceleration test using a high gradient cavity (HGC) loaded with magnetic alloy (MA) cores has been carried out at the HIMAC (Heavy Ion Medical Accelerator in Chiba). Acceleration of heavy ions, which required a wide frequency sweep from 1 MHz to 8 MHz, was successfully carried out without resonant frequency tuning.

A multi-orbit synchrotron (MOS) with fixed field alternating gradient (FFAG) focusing is attractive for acceleration of high intensity hadron beams because acceleration cycle could be increased. The magnetic field of MOS is static, therefore, the repetition rate of acceleration could be increased more than 10 times larger than that of ordinary rapid cycling synchrotron (RCS) if an efficient high voltage RF accelerating system becomes available. Recently, a new type of high gradient RF cavity (HGC) using high permeability magnetic alloy (MA) has been developed and MOS with FFAG focusing becomes very promising. In order to clarify the feasibility of rapid cycling MOS (RCMOS) experimentally, proof-of-principle (POP) machine, which accelerates protons up to 1 MeV with 1 kHz repetition, is under development. We have also made several designs on high intensity proton accelerators with RCMOS for various applications such as an accelerator driven system (ADS) as an energy breeder, a spallation neutron source and a proton driver for a muon collider.

A magnetic alloy (MA) loaded cavity which was developed by KEK was used for the barrier bucket experiment at the AGS. The MA loaded cavity could generate a single sine-wave of 40 kV with less RF power than a ferrite loaded cavity because of its broad-band impedance. In order to reduce the voltage induced by beam, the feedforward system was applied and the beam loading was compensated. With the barrier bucket scheme, five bunches were transferred successfully. Total of 3/spl times/10/sup 13/ protons were accumulated without beam loss. They were re-bunched by the accelerating cavities and accelerated.

We investigated the relation between multifocal electroretinograms (M-ERGs) and artificial parafoveal scotoma. M-ERGs were recorded from normal subjects using a circular piece of black paper attached to a monitor. Lower response density around the 10 to 15 degree parafovea region was not observed up to 3 degree scotoma (visual angle), but was detected above 5 degree scotoma in field topography of M-ERGs. The shape of the scotoma in field topography was not circular but somewhat oval. The results from two cases of parafoveal retinal degeneration were in good accordance with this basic study in normal subjects. We proved that detection of parafoveal scotoma by M-ERG is limited in comparison with the results obtained by automated static perimetry.

Ro 5-4864, a specific agonist of the peripheral-type benzodiazepine receptor (PBR), elicited convulsions 2.6 times more potently in EL mice (an animal model of epilepsy) than in DDY mice (control animal). A binding assay revealed a 50% higher density of [3H] Ro 5-4864 binding sites in the mitochondrial fraction (i.e., mitochondrial benzodiazepine receptors; MBR) of the brain tissues in EL mice as compared with DDY mice. On an elevated plus-maze, EL mice showed fear responses similar to those increased in DDY mice after PBR stimulation, suggesting a hyperfunction of MBR underlying the abnormal behaviors of EL mice. In fluorometric studies using NG108-15 cells, Ro 5-4864 depolarized mitochondrial membranes and, possibly as a consequence of this, raised intracellular Ca2+. Finally, we propose that MBR could be a major target of therapy for various neurological disorders, so drugs such as "mitochondrial membrane stabilizers" should be developed.

Avulsion of ureter without renal injury is rarely caused by blunt trauma, only 28 cases having been reported in Japan. A 33-year-old male was admitted to our hospital 1 month after blunt abdominal trauma at work. He complained of left flank pain and macroscopic hematuria. Under the suspicion of renal or ureteral injury, drip infusion urography and abdominal computerized tomography revealed an extravasation from the left upper ureter and urinoma formation in the retroperitoneal cavity. In order to reduce the inflammation, the urinoma was drained. The retrograde pyelogram revealed complete obstruction at the left upper ureter, 20 cm from the left ureteral orifice. Urinary tract reconstruction, end-to-end ureteral anastomosis, was performed under the diagnosis of left ureteral avulsion. Drip infusion urography revealed normal ureteral healing without stricture formation at 2 years after reconstruction.

The present study was designed to obtain evidence for direct interactions of G-protein alpha (Galpha) and beta gamma subunits (Gbeta gamma) with N- (alpha1B) and P/Q-type (alpha1A) Ca2+ channels, using synthetic peptides and fusion proteins derived from loop 1 (cytoplasmic loop between repeat I and II) and the C terminus of these channels. For N-type, prepulse facilitation as mediated by Gbeta gamma was impaired when a synthetic loop 1 peptide was applied intracellularly. Receptor agonist-induced inhibition of N-type as mediated by Galpha was also impaired by the loop 1 peptide but only when applied in combination with a C-terminal peptide. For P/Q-type channels, by contrast, the Galpha-mediated inhibition was diminished by application of a C-terminal peptide alone. Moreover, in vitro binding analysis for N- and P/Q-type channels revealed direct interaction of Galpha with C-terminal fusion proteins as well as direct interaction of Gbeta gamma with loop 1 fusion proteins. These findings define loop 1 of N- and P/Q-type Ca2+ channels as an interaction site for Gbeta gamma and the C termini for Galpha.

Interactions of G-protein alpha (Galpha) and beta gamma subunits (Gbeta gamma) with N- (alpha1B) and P/Q-type (alpha1A) Ca2+ channels were investigated using the Xenopus oocyte expression system. Gi3alpha was found to inhibit both N- and P/Q-type channels by receptor agonists, whereas Gbeta1 gamma2 was responsible for prepulse facilitation of N-type channels. L-type channels (alpha1C) were not regulated by Galpha or Gbeta gamma. For N-type, prepulse facilitation mediated via Gbeta gamma was impaired when the cytoplasmic I-II loop (loop 1) was deleted or replaced with the alpha1C loop 1. Galpha-mediated inhibitions were also impaired by substitution of the alpha1C loop 1, but only when the C terminus was deleted. For P/Q-type, by contrast, deletion of the C terminus alone diminished Galpha-mediated inhibition. Moreover, a chimera of L-type with the alpha1B loop 1 gained Gbeta gamma-dependent facilitation, whereas an L-type chimera with the N- or P/Q-type C terminus gained Galpha-mediated inhibition. These findings provide evidence that loop 1 of N-type channels is a regulatory site for Gbeta gamma and the C termini of P/Q- and N-types for Galpha.