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Pulmonary complications are frequent in patients with sickle cell disease (SCD), but few studies have described lung pathology in SCD. We studied the lung tissue of 30 deceased SCD patients (1994-2012). Demographics, genotype, clinical characteristics, cause of death and associated conditions are presented. We quantified the presence of pulmonary arterial changes, thrombosis and venous thickening. Alveolar capillary abnormalities were demonstrated using CD34 expression and confocal microscopy. Autopsy and echocardiography reports were reviewed to classify heart abnormalities. Tissue expression of markers of endothelial activation (vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and vascular endothelial growth factor) was quantified in pulmonary vessels. Median age was 33 years; genotype was SS in 19, SC in 7 and Sβ in 4, and there were 18 males. Hypertensive arterial changes were present in 76% of the patients, recent thrombosis in 80% and old thrombosis in 43%. Venous thickening was present in 23% and pulmonary capillary haemangiomatosis foci in 87%. Ten percent of the patients presented right ventricular hypertrophy. There was no increased expression of endothelial activation markers when compared to controls. SCD affects the whole pulmonary vascular tree and reflects the multiple burden on lung vasculature imposed by the disease upon time.

The Technical Design for the COMET Phase-I experiment is presented in this paper. COMET is an experiment at J-PARC, Japan, which will search for neutrinoless conversion of muons into electrons in the field of an aluminium nucleus ($\mu-e$ conversion, $\mu^- N \to e^- N$); a lepton flavor violating process. The experimental sensitivity goal for this process in the Phase-I experiment is $3.1\times10^{-15}$, or 90 % upper limit of branching ratio of $7\times 10^{-15}$, which is a factor of 100 improvement over the existing limit. The expected number of background events is 0.032. To achieve the target sensitivity and background level, the 3.2 kW 8 GeV proton beam from J-PARC will be used. Two types of detectors, CyDet and StrECAL, will be used for detecting the \mue conversion events, and for measuring the beam-related background events in view of the Phase-II experiment, respectively. Results from simulation on signal and background estimations are also described., Comment: A minor correction applied in Eq. 3

Background Patients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment. Methods Fifty severe asthmatics received prednisone 40 mg/d for 2 weeks and maintenance therapy with budesonide/formoterol 400/12 μg twice daily + budesonide/formoterol 200/6 μg as needed for 12 weeks. Endobronchial biopsies were performed at the end of 12 weeks. We performed extensive immunopathological analyses of airway tissue inflammation and remodeling features in patients stratified by asthma symptom control and by airflow obstruction. Results Airway tissue inflammation and remodeling were not associated with symptom control. Asthmatics with persistent airflow obstruction had greater airway smooth muscle (Asm) area with decreased periostin and transforming growth factor beta-positive cells within Asm bundles, in addition to lower numbers of chymase-positive mast cells in the submucosa compared to patients with nonpersistent obstruction. Conclusions Symptom control in severe asthmatics was not associated with airway tissue inflammation and remodeling, although persistent airflow obstruction in these patients was associated with bronchial inflammation and airway structural changes.

Compact Infrared Camera (CIRC) is a technology-demonstration instrument equipped with an uncooled infrared array detector (microbolometer) for space application. CIRC is the first microbolometer sensor without a calibration function in orbit, like a shutter system or an onboard blackbody. The main objective of the CIRC is to detect wildfires, which are major and chronic disasters affecting various countries of Southeast Asia, particularly considering the effects of global warming and climate change. The CIRC achieves a small size (approximately 200 mm), light mass (approximately 3 kg), and low electrical power consumption (

Laser-assisted magnetic recording is an interesting method for narrowing a track pitch; in particular, crosstalk canceling in laser-assisted magnetic readout has a unique feature that it enables us to reproduce a narrower track than an assisting laser spot size. Shorter wavelength of the assisting laser promises the higher track density, accordingly. In this paper, we have demonstrated the crosstalk evaluation by using a blue laser for the assisting beam and obtained as high track density as 85ktpi.

Recent progress in laser-assisted magnetic recording, which combines optical and magnetic recording technologies, is described in this paper. This study confirms that laser-assisted magnetic recording is a good candidate for high areal density magnetic recording. Improved disk performance was demonstrated in the area of frequency response, media noise, and thermal decay. The improvements in media design include the change in temperature dependence of the recording layer, an increased perpendicular anisotropy, and a thermally efficient layer structure. These improved media properties result in a high linear density and good thermal stability.

A series of pyrazole derivatives with two and three alkylating sites were prepared and their cytotoxicity against cancer cells as well as antitumor activity against L1210 was investigated. The best result of cytotoxicity was obtained with the trichloride 5 and the best antitumor activity (ILS 33%) with the dibromide 3. These results can provide valuable information for further study of the more effective antitumor agent. Keywords: pyrazole, synthesis, cytotoxicity, antitumor activity, polyalkylator.

A 65-year-old man was admitted to our department due to severe dysphagia, dysarthria, and aspiration pneumonia. Dysphagia and dysarthria were caused by lateral medullary infarction (Wallenberg' s syndrome). After the patient recovered from pneumonia, the abnormality of swallowing was assessed by a swallowing provocation test and videofluorography. Two months after the start of swallowing training, a swallowing provocation test showed that the swallowing reflex had improved and videofluorography showed that the magnitude of aspiration to the trachea had decreased. The patient began taking food by mouth. These tests are useful for quantitative assessment of dysphagia and for deciding when to start oral intake in elderly patients.

AC impedance method has been applied to evaluate the performance of Zn, Zn-5%Al and Zn-55%Al coated steels under wet-dry cycles. The wet-dry cycles were carried out by exposure to the alternate conditions of I h-immersion in a 0.5 or a 0.05 kmol/m 3 NaCl solution and drying for various times at 298 K and 60%RH. The impedances at two frequency points, a high frequency (10 kHz) and a low frequency (10 mHz), were monitored during the cyclic wet-dry exposure. The reciprocals of the high frequency and low frequency impedances were taken as the solution conductance of water layer on the coating surface and the corrosion rate of the coated steels, respectively. The impedance monitoring results showed that the Zn-55%Al coating exhibited the most excellent corrosion resistance under the given conditions. This is attributed to the formation of aluminum oxide on the specimen surface. On the other hand, the corrosion resistances of Zn coated and Zn-5%Al coated steels were almost the same under relatively wet and highly chloride-concentrated conditions. An increase in the chloride concentration of the test solution employed during the wet-dry cyclic test decreased the average corrosion rate in all cases. The average corrosion rate of the Zn-55%Al coating under a wet-dry cyclic condition in 0.5 kmol/m 3 NaCI solution was lower than that in 0.05 kmol/m 3 NaCI by one order of magnitude. The combined wet-dry cyclic exposure test and AC impedance corrosion monitoring is very useful for the mechanistic study of the corrosion of coated steels, as well as the evaluation of their corrosion performance, in marine atmospheric environments.

The corrosion rates of steels with different nickel contents (0, 2.5, 10 and 20 wt%) were monitored by the AC impedance method under a cyclic wet-dry condition, which was conducted by exposure to alternate conditions of 1 h immersion in a 0.05 M NaCl solution and 7 h drying at 60% RH and 25 °C. The corrosion rates of the ordinary carbon steel and the 2.5% Ni containing steel were greatly accelerated by the wet-dry cycles, while those of steels containing at least 5% Ni were only slightly affected. AC impedance tests indicated that the addition of 5% Ni greatly reduced the corrosion rates of the steel exposed to the cyclic wet-dry environments containing chloride ions, in good agreement with one year exposure tests in the atmospheric marine environments. Within the wet-dry cycle for the carbon steel, a gradual increase in the corrosion rate and a shift of the corrosion potential to negative values were observed at the initial stage of the drying period. These indicated that the anodic metal dissolution rate was accelerated by a slight increase in the chloride ion concentration. At the intermediate stage of drying, the corrosion rate rapidly increased and the corrosion potential remained constant. This can be attributed to the acceleration of both the anodic metal dissolution process and the cathodic oxygen reduction process which is usually controlled by the rates of O2 transport through the thin electrolyte film. At the final stage, just before the surface dried out, the corrosion rate rapidly decreased, shifting the corrosion potential to the noble direction. At this stage, the anodic process was greatly inhibited. The corrosion testing system employed in this study is very useful for the rapid evaluation of the corrosion performance of metals in atmospheric marine environments and for mechanistic study.

Aims: To develop time‐dependent dose–response models for highly pathogenic avian influenza A (HPAI) of the H5N1 subtype virus. Methods and Results: A total of four candidate time‐dependent dose–response models were fitted to four survival data sets for animals (mice or ferrets) exposed to graded doses of HPAI H5N1 virus using the maximum‐likelihood estimation. A beta‐Poisson dose–response model with the N 50 parameter modified by an exponential‐inverse‐power time dependency or an exponential dose–response model with the k parameter modified by an exponential‐inverse time dependency provided a statistically adequate fit to the observed survival data. Conclusions: We have successfully developed the time‐dependent dose–response models to describe the mortality of animals exposed to an HPAI H5N1 virus. The developed model describes the mortality over time and represents observed experimental responses accurately. Significance and Impact of the Study: This is the first study describing time‐dependent dose–response models for HPAI H5N1 virus. The developed models will be a useful tool for estimating the mortality of HPAI H5N1 virus, which may depend on time postexposure, for the preparation of a future influenza pandemic caused by this lethal virus.

Authors have proposed an asymmetrical associative neural network (NN) using variable hysteresis threshold and its learning and association algorithms. It can drastically improve noise performance, that is insensitivity to noise. In this paper, memory capacity bound and threshold optimization in this associative NN are further discussed. Binary random patterns are considered. First, relation between the number of patterns and the number of iterations is investigated. The latter gradually increases until some number of patterns. After that, it suddenly increases. This is a very peculiar phenomenon. This turning point gives the memory capacity bound, that is about 1.56N, where N is the number of units. Next, threshold optimization is discussed. Relation between threshold and noise performance, and effects of connection weight distribution on noise performance are theoretically discussed. Based on these results, a ratio of step-size and the threshold is optimized to be 0.5/(NP-1), where NP is the number of units on the pattern. Numerically statistical simulation demonstrates efficiency of the proposed methods.

Laser-assisted magnetic recording technology enables narrower track recording and reproducing than the track width of a magnetic head. The size of the assisting beam is a critical issue for high track density in this technology. In this study, the possibility of the 100 kTPI recording was demonstrated with laser-assisted magnetic recording using a blue laser.

The pole assignment problem is considered, using the graph representation of a matrix. The parametrization of controllers which have a specified characteristic polynomial is given. A simple algorithm based on graphs is presented and two examples are given. >

A new low-bit learning algorithm for digital multilayer neural networks applied to pattern recognition is proposed. The training can be carried out with a small number of bits. To make the neural network insensitive to noisy patterns, conditions to be satisfied by hidden layer outputs are discussed. Based on this, optimum targets are assigned to the hidden layers. Computer simulation demonstrated the efficiency of the proposed method. >

Two kinds of deadbeat control problems are considered. One is the state deadbeat control problem and the other is the pointwise minimum-time deadbeat control problem. A simple graph called the state transition graph of a matrix is introduced, and simple algorithms based on it giving deadbeat controllers are presented. The set of pointwise minimum-time deadbeat controllers is characterized. The set of output feedback deadbeat controller is also considered. >

The aim of this study was to investigate the influence of endothelin-1 (ET-1) on the pulmonary and systemic circulations in newborn piglets. Twelve piglets (mean age of 6.8 days, range of 1-12 days) were anesthetized with chloralose-urethane and ventilated at FiO2 = 1.0. Animals were instrumented to measure cardiac output (CO), pulmonary artery pressure (PAP), aortic pressure (AoP), left atrial pressure (LAP), and right atrial pressure (RAP). Six piglets received a control saline injection into the pulmonary artery (PA), and six piglets received one injection of ET-1 (500 ng/kg) into the PA while PAP, AoP, LAP, RAP, CO, and heart rate (HR) were measured simultaneously at 20-s intervals with pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) calculated by computer. Administration of ET-1 into the PA led to (a) a transient decrease in mean PAP (delta max of -4 +/- 2 mm Hg, p less than 0.001); (b) a biphasic response (an initial decline followed by a substantial increase) in PVR (delta max of -760 +/- 460 dyn cm/s5, p less than 0.01, and delta max of +1,490 +/- 1,360 dyn cm/s5, p less than 0.05) and in AoP (delta max of -12 +/- 7 mm Hg, p less than 0.005, and delta max of +11 +/- 6 mm Hg, p less than 0.005); (c) an increase in SVR (delta max of +5,930 +/- 2,330 dyn cm/s5, p less than 0.05); and (d) an initial increase in CO (delta max of +0.06 +/- 0.03 L/min, p less than 0.05) followed by a decrease (delta max of -0.09 +/- 0.05 L/min, p less than 0.05). These responses have not been observed in adult species and may indicate a developmental difference in the response of the pulmonary circulation to ET-1 administration.

症例:72歳,男性.主訴は便秘.注腸X線検査では,虫垂が造影されず,盲腸底部に径約2cm大の隆起があり,その中央に小隆起を認めた.大腸内視鏡検査では,虫垂開口部が腫大し,その中心に小隆起を認めた.同部からの生検ではリンパ濾胞過形成がみられた.腹部US,腹部CT検査では回盲部に径約1.5～2.0cm,長さ約5cm大,嚢状に腫大した虫垂を認めた.虫垂嚢胞と診断したが,悪性病変の合併を否定し得ず,回盲部切除を施行.肉眼的には棍棒状に腫大し,波動感を伴う虫垂であり割面では虫垂開口部はリンパ濾胞過形成や炎症性変化で閉塞されていた.組織学的には腫瘍細胞はみられず,retention cystと診断された.嚢胞内容液CEA値は2000ng/ml以上(血中CEA値1.3ng/ml)と高値を呈していた,この様な症例の報告は見当らず,若干の文献的考察を加えた

Pulsed dielectric barrier discharges are generated within bubbles of a gas-liquid two-phase flow that consists of argon bubbles and water. Discharge images were captured by using a high-speed video camera to understand the motion of discharge within bubbles, and an intensified charge-coupled device camera captured temporal discharge images at a nanosecond timescale.

Video signal processing for compatible analog HD (high-definition) VCRs in baseband/MUSE modes for consumer use with simple signal processors supporting 2/4-hour recording and search display is discussed. These HD VCRs permit long-time recording and multispeed playback functions similar to those of conventional VCRs. It was confirmed that not only do these VCRs satisfy specifications required for consumer use HD VCRs, but they also demonstrate the possibility of realizing a small-size, inexpensive, and low-power-consumption HD VCR. >

For estrogen-responsive B-1F cells, established from estrogen-responsive mouse Leydig cell tumor, it has been reported that the 5-lipoxygenase (5-LOX) metabolic pathway appears to be associated with cell growth. The addition of 5-LOX inhibitor 2-(12-hydroxydodeca-5,10-diyl)-3,5,6-trimethyl-1,4-benzoquinone (AA861) to the medium resulted in a dose-dependent increase in cell yield as described previously. When the growth of the palpable tumors was measured, AA861 had stimulated in vivo tumor growth in adult male mouse inoculated B-1F cells. The effects of AA861 and 17beta-estradiol (E2) on the contents of various arachidonic acid metabolites in B-1F cells and their conditioned medium were examined. Although AA861 and E2 decreased the contents of leukotrienes (LTs), the two did not significantly change those of prostaglandins, thromboxan, prostacyclin, 12-hydroxyeicosatetraenoic acid (HETE) and 15-HETE. In immunohistochemical study B-1F cells show positive staining for 5-LOX in the E2-depleted condition, while E2 decreased the expression of 5-LOX. The decrease of the intensities of 79-kDa 5-LOX protein and 403-bp RT-PCR product bands was observed. The growth of Morpholino-anti oligo delivered B-1F cells was higher than that of Standard control oligo delivered cells. The delivery of Morpholino-anti oligo into B-1F cells caused the decrease of contents of LTs and 5-HETE in the cells and medium, and the reduction of 5-LOX activity. When LTD4 was added in the culture medium, the increasing concentrations of LTD4 resulted in a significant inhibition of cell yields of E2-treated B-1F cells. Morphological changes such as nuclear condensation and fragmentation, and DNA ladder pattern were demonstrated in E2-stimulated B-1F cells treated with LTD4 as well as in control cells cultured in the basal medium. These results implicate that 5-LOX at least plays an important role in the growth of B-1F cells and LD4 induces the apoptosis of B-1F cells.

In the handwritten character recognition, it is very important to extract essential structure of character patterns. Requirements for skeletonization can be summarized as follows: (a) Insensitive to irregular edge lines. (b) Nonstructure patterns are not extracted. (c) Insensitive to nonuniform line width. (d) Line information is held. In this paper, a weighted competitive learning method is proposed in order to achieve the above requirements. Regarding (a) and (b), unnecessary pattern information is removed by representing some region of the pattern using a single representative point (RP). In order to optimize the RPs, the competitive learning is employed. For the requirement (c), the region, covered by a RP, is adjusted according to the line width. The condition (d) is satisfied by connecting the RPs along the line and also through the border of the regions. Simulation results, obtained using so many kinds of distorted patterns, including digits, alphabet and Japanese Kanji, demonstrate the proposed method can extract essential skeleton structure despite of several distortions.

A hybrid multilayer neural network and its low-bit learning algorithm for binary pattern classification are proposed. In the training process, a single-layer network is first employed. If the training does not converge, then a middle unit is assigned to a critical pattern. Connection weights are adjusted so that this unit responds to the critical pattern. The training is repeated by increasing the middle units. Thus, the number of middle units can be optimized. Connection weights are adjusted using a small number of bits, resulting in very simplified digital hardware. Since the outputs of the middle and the output layers are specified, a single-layer low-bit learning algorithm is proposed. The training is very fast and is insensitive to initial weights and parameters. A divided form is proposed in order to drastically save the middle units for a large number of the patterns. >

We have investigated the background properties of EPIC-pn onboard XMM-Newton to establish the background subtraction method. Count rates of the background vary violently by two orders of magnitude at the maximum, while during the most quiet period, these are stable within 8 % at a 1 $\sigma$ level. The overall spectrum is dominated by particle events above 5 keV, and its spatial variation is also found. The long-term variation of the background is also investigated with CAL CLOSED data, where the filter wheel was in closed position with the internal calibration source illuminating the sensitive area. The average background count rate decreased by 20 % from March 2000 to January 2001, but it regained in February 2001. For the modeling of the background spectrum, we investigate relations between the 2.0--7.0 keV count rate and some characteristic parameters. The 2.0--7.0 keV background count rate shows a good correlation with the count rate of events outside the field of view. This correlation is usable for the modeling of the background., Comment: 9 pages, submitted to A&A

The structure activity relationship (SAR) in the anti-cancer activities of pyrazolo[1,5-a]indole derivatives was investigated, and the following conclusions were obtained: 1) N(1)-quaternarization is essential for anti-cancer activity, 2) the size and polarity of the 2-substituent is crucial for in vitro activity which allows further investigation in an in vivo test, 3) the effect of the 4-substituent on the activity is minor compared with the other two factors.

The purpose of this work was to develop functional parameters to analyze regional cardiac function using ECG-gated 99mTc-tetrofosmin SPECT. Our goal was to develop a methodology that used slice thickness correction, the generation of a time-activity curve and a polar map.Fourteen normal patients without evidence of coronary artery disease were studied. One hour after intravenous injection of 740-1110 MBq (20-30 mCi) 99mTc-tetrofosmin, ECG-gated SPECT data were acquired by dividing a cardiac cycle into 12 frames. The SPECT data were reconstructed from 11 of 12 frames into 3 views. The reconstruction of these images was repeated after performing slice thickness correction. Excluding the effect of different apex-to-base lengths at any frame during a cardiac cycle, 10 short-axis images with the same slice thickness were obtained. Each short-axis image was divided by 40 radii into 40 segments. The time-activity curve was generated from the total counts included in each segment plus both neighboring segments. Subsequently the curve fitting was performed using the second Fourier function.From fitted curves and their differentials, we calculated end-systolic count, end-diastolic count, percent count increase, uptake, peak contraction rate, peak distention rate and contraction time.The functional polar maps visually demonstrated regional myocardial function. This method is expected to be helpful for assessing regional cardiac function using 99mTc-tetrofosmin.

The intracellular mechanism of vasoactive intestinal peptide (VIP)-induced, charybdotoxin (ChTx)-sensitive relaxation of longitudinal muscle of the distal colon of Wistar-ST rats was studied. A single pulse or 100 pulses at 10 Hz of electrical field stimulation (EFS) induced rapid transient relaxation or that with a subsequent contraction of the longitudinal muscle in the presence of atropine and guanethidine, respectively. Rp-8 bromo cAMPS, an inhibitor of cyclic AMP dependent protein kinase (PKA), at 30 microM inhibited the relaxations induced by EFS with a single or 100 pulses maximally by about 80 or 60%, respectively. It also inhibited VIP (300 nM)-induced relaxation by 82%. VIP (100 nM - 1 microM) increased the cyclic AMP content of longitudinal muscle myenteric plexus preparations obtained from the distal colon. ChTx at 100 nM almost completely inhibited 8 bromo cyclic AMP-induced relaxation of the distal segments. EFS with two or three pulses at 10 Hz induced inhibitory junction potentials consisting of two phases, rapid and subsequent slow hyperpolarization in the membrane potential of longitudinal smooth muscle cells. Rp-cAMPS, another inhibitor of PKA, inhibited the delayed slow hyperpolarization. It also inhibited the exogenously added VIP-induced hyperpolarization of the cell membrane. Thus, the present study suggests that activation of PKA via activation of VIP receptors is associated with activation of ChTx-sensitive K(+) channels in relaxation of longitudinal muscle of the distal colon of Wistar-ST rats. British Journal of Pharmacology (2000) 129, 140 - 146

Aurora- and Ipl1-like midbody-associated protein (AIM-1) is a serine/ threonine kinase that is structurally related to Drosophila aurora and Saccharomyces cerevisiae Ipl1, both of which are required for chromosome segregation. A kinase-negative form of AIM-1 inhibits the formation of cleavage furrow without affecting nuclear division, indicating that the gene controls entry into cytokinesis during M phase in mammalian cells. A human gene that encodes the protein AIM-1 was overexpressed in colorectal and other tumor cell lines. The regulation of AIM-1 expression was cell cycle dependent in normal and tumor cells, and the maximum accumulation was observed at G2-M. Exogenous overexpression of wild-type AIM-1 produced multinuclearity in human cells, suggesting that the excess amount of AIM-1 had a dominant-negative effect on the overexpressing cells. In long-term culture of AIM-1-overexpressing cells, multiple nuclei in a cell were occasionally fused, and then an increased ploidy and aneuploidy were induced. Thus, the overexpression of AIM-1 in colorectal tumor cell lines is thought to have a causal relationship with multinuclearity and increased ploidy. Cytokinesis error caused by AIM-1 overexpression is a major factor in the predisposition of tumor cells to the perturbation of chromosomal integrity that is commonly observed in human neoplasia. Thus, defects of pathways essential for mitotic regulation are important during human cancer development.

It has been suggested that pulmonary rehabilitation compined with inspiratory muscle training (IMT) might improve pulmonary function and respiratory muscle strength in elderly patients with chronic obstructive pulmonary disease (COPD). To test this hypothesis, inspiratory muscle strength (PImax), expiratory muscle strength (PEmax) and resting pulmonary function were measured in 13 elderly patients with COPD (aged 70.3 +/- 2.7 years). Inspiratory muscle training (IMT) was performed for 15 min twice a day, using a pressure threshold device, for a total of 12 weeks. The inspiratory threshold was set at 15% of maximal inspiratory pressure (PImax) for each individual. Pulmonary rehabilitation was performed for 12-h sessions over a 12-week period. Patients with COPD were assigned randomly to two groups: pulmonary rehabilitation combined with IMT (group A) (n = 7), and conventional pulmonary rehabilitation only (group B) (n = 6). Functional residual capacity (FRC) decreased significantly from 4.3 +/- 0.4 L at baseline to 3.9 +/- 0.4 L after rehabilitation (p0.01), Vp significantly increased from 4.6 +/- 0.8 L/sec at baseline to 5.1 +/- 0.7 L/sec after rehabilitation (p0.05) and the PImax increased significantly from 51.5 +/- 5.4 cmH2O at baseline to 80.9 +/- 7.0 cmH2O after rehabilitation (p0.02) in group A. However, these variables did not change in group B. There was no improvement in the 10-minutes walking distance of group A, but there was a significant increase in that of group B. It can be concluded that pulmonary rehabilitation combined with IMT improves pulmonary function and inspiratory muscle strength in elderly patients with COPD.

Fogo Selvagem (FS) is an autoimmune disease characterized by subcorneal vesicles and antidesmoglein-1 autoantibodies. Previous epidemiologic data have linked the onset of FS to exposure to an environmental antigen(s). This investigation describes a unique human settlement with an extraordinarily high prevalence of FS. This community is made up of Amerindians belonging to the Terena tribe, which has settled on the Limao Verde reservation in the state of Mato Grosso do Sul in Brazil. Twenty-six well-characterized FS cases have been identified within a total population of 998, yielding a prevalence of 2.6%. Seventeen of the patients (65 %) were males, and over 50% were older than 30 y of age. The incidence of the disease shows temporal periodicity, i.e., years with several cases of FS alternating with years with no cases. Over one-half of the cases occurred in genetically related family members. Another Terena reservation, the Ipegue/Taunay, located 90 km west of the Limao Verde reservation, was also evaluated as a control group. This reservation, with a population of 2203, had no recorded cases of FS. Thus, the Limao Verde reservation represents a new focus of FS in which the disease exhibits temporal, geographic, and familial clustering. These results suggest that the environmental antigen or antigens precipitating FS are endemic to the Limao Verde reservation. This reservation appears to be an ideal population for carrying out sero-epidemiologic, genetic, and environmental studies aimed at disclosing the etiology of FS.

SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly post-translational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand–glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.

Japan Clinical Oncology Group (JCOG) is the largest cooperative group in Japan. The yearly accrual of 2011 was 2744 in total. Currently, there are 30 trials on accrual and 20 trials on follow-up. Those trials are supported by about 40 staffs including 5 physicians in JCOG DC/OPS. JCOG has now 15 study groups and has an established peer-review system for protocol and adverse events. There are 180 participating institutions and all roster information is managed in JCOG DC/OPS. JCOG DC/OPS issues monitoring reports for all studies twice a year. Until now, 25 JCOG studies were adopted as a reference of various cancer treatment guidelines.Current challenges in JCOG DC/OPS are as follow: (i) streamlining study process. The project for protocol development acceleration has been activated since 2009. The speed has been improved afterward and the shortest duration from concept approval to protocol approval is 173 days. Acceleration of manuscript writing is also underway. (ii) Correlative studies and biospecimen repository. Recently the demand for correlative studies is growing. We have implemented several correlative studies along with regular JCOG studies and accumulated the know-how in such type of studies. In addition, JCOG biospecimen repository has been established and specimens are to be collected under the common procedure before long. (iii) Promotion of ‘Kodo-iryo’ trials. JCOG is now planning two ‘Kodo-iryo’ trials (clinical trials using the evaluation system of investigational medical care). We are now developing a standardized procedure for conducting future ‘Kodo-iryo’ trials more smoothly. (iv) International collaborative trials. JCOG is now conducting two international collaborative studies. The harmonization of database definitions is sometimes hard and the number of staffs is not enough to handle many international trials. (v) Introduction of remote data entry system. In JCOG, all forms are still paper-based. It is mainly due to few supports by clinical research coordinator in the participating institutions. On the other hand, the yearly accrual becomes more and now we are considering introducing remote data entry system. Through all of those challenges, we aim to conduct well-designed, high-quality clinical trials rapidly and establish a large number of new standard treatments for cancer patients.

It is believed that hydrogen in silicon is located at the bond center. But, the hydrogen atom is actually deviated significantly from the bond center dynamically, which is illustrated by the present calculations. The fast relaxation to bending causes a large decay rate of the H vibration.