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The INBUILD trial investigated the efficacy and safety of nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF). We aimed to establish the effects of nintedanib in subgroups based on ILD diagnosis., info:eu-repo/semantics/published

Purpose To evaluate four-dimensional computed tomography (4D-CT)-derived pulmonary ventilation by comparing with 81m Kr-gas ventilation (V RI ). We also proposed two methods to improve the functional accuracy of 4D-CT ventilation images and evaluated these methods. Methods and materials Eleven lung cancer patients with 4D-CT and V RI were analyzed. Hounsfield unit-based (V HU ) and a Jacobian-based (V Jac ) 4D-CT ventilation images were calculated. They were evaluated by voxel-by-voxel spearman's rank correlation coefficient ( r ) between 4D-CT ventilation and V RI images. After applying an averaging ventilation method and a slope calculating method, correlations were also calculated. Results 4D-CT ventilation showed the high correlation to V RI ( r =0.875 with V HU ). An averaging method brought significantly higher ( p =0.012) correlations to nuclear medicine images with V HU . The improvement was not significant ( p =0.619) with V Jac . Slope calculating method improved the correlation with V HU and slightly worsened the correlation with V Jac . Conclusions The averaging method we proposed might be useful to improve 4D-CT ventilation images. We found good agreement between 4D-CT ventilation and nuclear medicine ventilation, indicating the high physiologic accuracy of 4D-CT ventilation.

The purpose of this study was to evaluate the accuracy of commercially available software, using patient DVH‐based QA metrics, by investigating the correlation between estimated 3D patient dose and magnitude of MLC misalignments. We tested 3DVH software with an ArcCHECK. Two different calculating modes of ArcCHECK Planned Dose Perturbation (ACPDP) were used: “Normal Sensitivity” and “High Sensitivity”. Ten prostate cancer patients treated with hypofractionated VMAT (67.6 Gy/26 Fr) in our hospital were studied. For the baseline plan, we induced MLC errors (−0.75,−0.5,−0.25,0.25,0.5, and 0.75 mm for each single bank). We calculated the dose differences between the ACPDP dose with error and TPS dose with error using gamma passing rates and using DVH‐based QA metrics. The correlations between dose estimation error and MLC position error varied with each structure and metric. A comparison using 1%/1 mm gamma index showed that the larger was the MLC error‐induced, the worse were the gamma passing rates. Slopes of linear fit to dose estimation error versus MLC position error for mean dose and D95 to the PTV were 1.76 and 1.40% mm−1, respectively, for “Normal Sensitivity”, and −0.53 and 0.88% mm−1, respectively, for “High Sensitivity”, showing better accuracy for “High Sensitivity” than “Normal Sensitivity”. On the other hand, the slopes for mean dose to the rectum and bladder, V35 to the rectum and bladder and V55 to the rectum and bladder, were −1.00,−0.55,−2.56,−1.25,−3.53, and 1.85% mm−1, respectively, for “Normal Sensitivity”, and −2.89,−2.39,−4.54,−3.12,−6.24, and −4.11% mm−1, respectively, for “High Sensitivity”, showing significant better accuracy for “Normal Sensitivity” than “High Sensitivity”. Our results showed that 3DVH had some residual error for both sensitivities. Furthermore, we found that “Normal Sensitivity” might have better accuracy for the DVH metric for the PTV and that “High Sensitivity” might have better accuracy for DVH metrics for the rectum and bladder. We must be willing to tolerate this residual error in clinical care. PACS number: 87.55Qr

Information on the distribution and biology of the G-protein coupled receptor 4 (GPR4) in the brain is limited. It is currently thought that GPR4 couples to Gs proteins and may mediate central respiratory sensitivity to CO2. Using a knock-in mouse model, abundant GPR4 expression was detected in the cerebrovascular endothelium and neurones of dorsal raphe, retro-trapezoidal nucleus locus coeruleus and lateral septum. A similar distribution was confirmed using RNAscope in situ hybridisation. In HEK293 cells, overexpressing GPR4, it was highly constitutively active at neutral pH with little further increase in cAMP towards acidic pH. The GPR4 antagonist NE 52-QQ57 effectively blocked GPR4-mediated cAMP accumulation (IC50 26.8 nM in HEK293 cells). In HUVEC which natively express GPR4, physiological acidification (pH 7.4–7.0) resulted in a cAMP increase by ∼55% which was completely prevented by 1 μM NE 52-QQ57. The main extracellular organic acid, l-lactic acid (LL; 1–10 mM), suppressed pH dependent activation of GPR4 in HEK293 and HUVEC cells, suggesting allosteric negative modulation. In unanaesthetised mice and rats, NE 52-QQ57 (20 mg kg−1) reduced ventilatory response to 5 and 10% CO2. In anaesthetised rats, systemic administration of NE 52-QQ57 (up to 20 mg kg−1) had no effect on hemodynamics, cerebral blood flow and blood oxygen level dependent responses. Central administration of NE 52-QQ57 (1 mM) in vagotomised anaesthetised rats did not affect CO2-induced respiratory responses. Our results indicate that GPR4 is expressed by multiple neuronal populations and endothelium and that its pH sensitivity is affected by level of expression and LL. NE 52-QQ57 blunts hypercapnic response to CO2 but this effect is absent under anaesthesia, possibly due to the inhibitory effect of LL on GPR4.

Deformable image registration (DIR) is fundamental technique for adaptive radiotherapy and image-guided radiotherapy. However, further improvement of DIR is still needed. We evaluated the accuracy of B-spline transformation-based DIR implemented in elastix. This registration package is largely based on the Insight Segmentation and Registration Toolkit (ITK), and several new functions were implemented to achieve high DIR accuracy. The purpose of this study was to clarify whether new functions implemented in elastix are useful for improving DIR accuracy. Thoracic 4D computed tomography images of ten patients with esophageal or lung cancer were studied. Datasets for these patients were provided by DIR-lab (dir-lab.com) and included a coordinate list of anatomical landmarks that had been manually identified. DIR between peak-inhale and peak-exhale images was performed with four types of parameter settings. The first one represents original ITK (Parameter 1). The second employs the new function of elastix (Parameter 2), and the third was created to verify whether new functions improve DIR accuracy while keeping computational time (Parameter 3). The last one partially employs a new function (Parameter 4). Registration errors for these parameter settings were calculated using the manually determined landmark pairs. 3D registration errors with standard deviation over all cases were 1.78 (1.57), 1.28 (1.10), 1.44 (1.09) and 1.36 (1.35) mm for Parameter 1, 2, 3 and 4, respectively, indicating that the new functions are useful for improving DIR accuracy, even while maintaining the computational time, and this B-spline-based DIR could be used clinically to achieve high-accuracy adaptive radiotherapy.

Purpose The purpose of this study was to estimate the accuracy of the dose calculation of On-Board Imager (Varian, Palo Alto, CA) cone beam computed tomography (CBCT) with deformable image registration (DIR), using the multilevel-threshold (MLT) algorithm and histogram matching (HM) algorithm in pelvic radiation therapy. Methods and Materials One pelvis phantom and 10 patients with prostate cancer treated with intensity modulated radiation therapy were studied. To minimize the effect of organ deformation and different Hounsfield unit values between planning CT (PCT) and CBCT, we modified CBCT (mCBCT) with DIR by using the MLT (mCBCT MLT ) and HM (mCBCT HM ) algorithms. To evaluate the accuracy of the dose calculation, we compared dose differences in dosimetric parameters (mean dose [D mean ], minimum dose [D min ], and maximum dose [D max ]) for planning target volume, rectum, and bladder between PCT (reference) and CBCTs or mCBCTs. Furthermore, we investigated the effect of organ deformation compared with DIR and rigid registration (RR). We determined whether dose differences between PCT and mCBCTs were significantly lower than in CBCT by using Student t test. Results For patients, the average dose differences in all dosimetric parameters of CBCT with DIR were smaller than those of CBCT with RR (eg, rectum; 0.54% for DIR vs 1.24% for RR). For the mCBCTs with DIR, the average dose differences in all dosimetric parameters were less than 1.0%. Conclusions We evaluated the accuracy of the dose calculation in CBCT, mCBCT MLT , and mCBCT HM with DIR for 10 patients. The results showed that dose differences in D mean , D min , and D max in mCBCTs were within 1%, which were significantly better than those in CBCT, especially for the rectum ( P MLT and mCBCT HM can be useful for improving the dose calculation for adaptive radiation therapy.

We evaluated the accuracy of one commercially available and three publicly available deformable image registration (DIR) algorithms for thoracic four-dimensional (4D) computed tomography (CT) images. Five patients with esophagus cancer were studied. Datasets of the five patients were provided by DIR-lab (dir-lab.com) and consisted of thoracic 4D CT images and a coordinate list of anatomical landmarks that had been manually identified. Expert landmark correspondence was used for evaluating DIR spatial accuracy. First, the manually measured displacement vector field (mDVF) was obtained from the coordinate list of anatomical landmarks. Then the automatically calculated displacement vector field (aDVF) was calculated by using the following four DIR algorithms: B-spine implemented in Velocity AI (Velocity Medical, Atlanta, GA, USA), free-form deformation (FFD), Horn–Schunk optical flow (OF) and Demons in DIRART of MATLAB software. Registration error is defined as the difference between mDVF and aDVF. The mean 3D registration errors were 2.7 ± 0.8 mm for B-spline, 3.6 ± 1.0 mm for FFD, 2.4 ± 0.9 mm for OF and 2.4 ± 1.2 mm for Demons. The results showed that reasonable accuracy was achieved in B-spline, OF and Demons, and that these algorithms have the potential to be used for 4D dose calculation, automatic image segmentation and 4D CT ventilation imaging in patients with thoracic cancer. However, for all algorithms, the accuracy might be improved by using the optimized parameter setting. Furthermore, for B-spline in Velocity AI, the 3D registration error was small with displacements of less than ∼10 mm, indicating that this software may be useful in this range of displacements.

Our aim was to investigate the feasibility of a three-dimensional (3D) -printed head-and-neck (HN) immobilization device by comparing its positional accuracy and dosimetric properties with those of a conventional immobilization device (CID). We prepared a 3D-printed immobilization device (3DID) consisting of a mask and headrest with acrylonitrile-butadiene-styrene resin developed from the computed tomography data obtained by imaging a HN phantom. For comparison, a CID comprising a thermoplastic mask and headrest was prepared using the same HN phantom. We measured the setup error using the ExacTrac X-ray image system. Furthermore, using the ionization chamber and the water-equivalent phantom, we measured the changes in the dose due to the difference in the immobilization device material from the photon of 4 MV and 6 MV. The positional accuracy of the two devices were almost similar in each direction except in the vertical, lateral, and pitch directions (t-test, p

The Los Angeles classification system is the most widely employed criteria associated with the greatest interobserver agreement among endoscopists. In Japan, the Los Angeles classification system has been modified (modified LA system) to include minimal changes as a distinct grade of reflux esophagitis, rather than as auxiliary findings. This adds a further grading M defined as minimal changes to the mucosa, such as erythema and/or whitish turbidity. The modified LA system has come to be used widely in Japan. However, there have been few reports to date that have evaluated the interobserver agreement in diagnosis when using the modified LA classification system incorporating these minimal changes as an additional grade. A total of 100 endoscopists from university hospitals and community hospitals, as well as private practices in the Osaka-Kobe area participated in the study. A total of 30 video clips of 30-40 seconds duration, mostly showing the esophagocardiac junction, were created and shown to 100 endoscopists using a video projector. The participating endoscopists completed a questionnaire regarding their clinical experience and rated the reflux esophagitis as shown in the video clips using the modified LA classification system. Agreement was assessed employing kappa (kappa) statistics for multiple raters. The kappa-value for all 91 endoscopists was 0.094, with a standard error of 0.002, indicating poor interobserver agreement. The endoscopists showed the best agreement on diagnosing grade A esophagitis (0.167), and the poorest agreement when diagnosing grade M esophagitis (0.033). The kappa-values for the diagnoses of grades N, M, and A esophagitis on identical video pairs were 0.275-0.315, with a standard error of 0.083-0.091, indicating fair intraobserver reproducibility among the endoscopists. The study results consistently indicate poor agreement regarding diagnoses as well as fair reproducibility of these diagnoses by endoscopists using the modified LA classification system, regardless of age, type of practice, past endoscopic experience, or current workload. However, grade M reflux esophagitis may not necessarily be irrelevant, as it may suggest an early form of reflux disease or an entirely new form of reflux esophagitis. Further research is required to elucidate the pathophysiological basis of minimal change esophagitis.

The insular cortex is located in the centre of the cerebral hemisphere, having connections with the primary and secondary somatosensory areas, anterior cingulate cortex, amygdaloid body, prefrontal cortex, superior temporal gyrus, temporal pole, orbitofrontal cortex, frontal and parietal opercula, primary and association auditory cortices, visual association cortex, olfactory bulb, hippocampus, entorhinal cortex, and motor cortex. Accordingly, dense connections exist among insular cortex neurons. The insular cortex is involved in the processing of visceral sensory, visceral motor, vestibular, attention, pain, emotion, verbal, motor information, inputs related to music and eating, in addition to gustatory, olfactory, visual, auditory, and tactile data. In this article, the literature on the relationship between the insular cortex and neuropsychiatric disorders was summarized following a computer search of the Pub-Med database. Recent neuroimaging data, including voxel based morphometry, PET and fMRI, revealed that the insular cortex was involved in various neuropsychiatric diseases such as mood disorders, panic disorders, PTSD, obsessive-compulsive disorders, eating disorders, and schizophrenia. Investigations of functions and connections of the insular cortex suggest that sensory information including gustatory, olfactory, visual, auditory, and tactile inputs converge on the insular cortex, and that these multimodal sensory information may be integrated there.

The In-site of Ba2In2O5 with Brownmillerite structure was partially substituted for Ce4+ ions in order to examine the doping effect on the order-disorder transition. Ba2In2 − xCexO5 + x/2 (x = 0.1, 0.2, 0.3, 0.5, 1.0, and 1.5) were prepared by solid state reaction. X-Ray diffraction analyses of these powder samples demonstrated that Ba2In2 − xCexO5 + x/2 (x = 0.1 and 0.2) possesses Brownmillerite structure. With increasing content of Ce4+ ion the crystal system of Ba2In2 − xCexO5 + x/2 (x = 0.3, 0.5, and 1.0) changed to cubic perovskite structure above the order-disorder transition temperature of Ba2In2O5. Arrhenius plots of the electrical conductivities of Ba2In2 − xCexO5 + x/2 (x = 0.2, 0.3, and 1.0) exhibited no discontinuity. These compounds had high transference numbers of oxide ion above 973 k.

Irregular breathing can influence the outcome of four-dimensional computed tomography imaging for causing artifacts. Audio-visual biofeedback systems associated with patient-specific guiding waveform are known to reduce respiratory irregularities. In Japan, abdomen and chest motion selfcontrol devices (Abches), representing simpler visual coaching techniques without guiding waveform are used instead; however, no studies have compared these two systems to date. Here, we evaluate the effectiveness of respiratory coaching to reduce respiratory irregularities by comparing two respiratory management systems. We collected data from eleven healthy volunteers. Bar and wave models were used as audio-visual biofeedback systems. Abches consisted of a respiratory indicator indicating the end of each expiration and inspiration motion. Respiratory variations were quantified as root mean squared error (RMSE) of displacement and period of breathing cycles. All coaching techniques improved respiratory variation, compared to free-breathing. Displacement RMSEs were 1.43 ± 0.84, 1.22 ± 1.13, 1.21 ± 0.86, and 0.98 ± 0.47 mm for free-breathing, Abches, bar model, and wave model, respectively. Freebreathing and wave model differed significantly (p < 0.05). Period RMSEs were 0.48 ± 0.42, 0.33 ± 0.31, 0.23 ± 0.18, and 0.17 ± 0.05 s for free-breathing, Abches, bar model, and wave model, respectively. For variation in both displacement and period, wave model was superior to free-breathing, bar model, and Abches. The average reduction in displacement and period RMSE compared with wave model were 27% and 47%, respectively. The efficacy of audio-visual biofeedback to reduce respiratory irregularity compared with Abches. Our results showed that audio-visual biofeedback combined with a wave model can potentially provide clinical benefits in respiratory management, although all techniques could reduce respiratory irregularities.

A 39-year-old man was admitted to our hospital for further evaluation of a consolidated shadow and clarification of the cause of serum tumor marker elevation (CA19-9 496.2 U/ml, CA125 160.6 U/ml). Chest computed tomography revealed a well-defined homogeneous nodule in the left S10. Angiography showed one aberrant artery, branching from the ascending aorta. Intralobar pulmonary sequestration was diagnosed and the sequestrated lung was resected. Microscopic findings of the sequestrated lung showed a mucus-containing cystically dilated bronchus, which was covered with ciliated cylindrical epithelium. Immunohistochemical staining showed positive staining for CA19-9 and CA125 in both the ciliated cylindrical epithelium and mucus. Serum values of tumor markers returned to their normal range after surgery.(Internal Medicine 41: 875-878, 2002)

We have studied thermally induced coarsening process in bilayer islands of ordered Al–Pd surface alloy on Pd(0 0 1). The island size distribution was deduced from scanning tunneling microscopy images recorded after annealing the surface at 500–700 K. Normalized size distribution function after annealing at 500 K, at which temperature the bilayer surface alloy is formed, shows a sharp peak at u∼0.2, where u denotes the island size normalized to the average size, with a long tail extending to u∼4. Upon annealing at higher temperatures, the peak shifts to larger u and gets broader. After annealing at 700 K, at which temperature the decomposition of surface alloy sets in, the normalized distribution function resembles closely the universal scaling function predicted for coarsening due to diffusion and coalescence of two-dimensional islands. The data is not consistent with the Ostwald ripening.

The oxidation of the Au-deposited Si(1 1 1)-7×7 surface has been studied by scanning tunneling microscopy. The oxidation of Si adatoms is inhibited even at low Au coverages, where Au atoms are mainly adsorbed on the Si rest atoms. The effect on the chemical reactivity is correlated with the changes in the electronic state of the neighboring Si adatoms by Au adsorbed on the rest atoms. At higher coverages, inhibition of the oxidation is explained by the sterical blocking of the adsorption sites. It has also been found that Au clusters on the Si(1 1 1) surface are not active with respect to oxygen at room temperature.

To investigate the possible role of hepatocyte growth factor (HGF) in the reconstruction process following inflammatory damage in lung tissue, we compared HGF production of human lung microvascular endothelial cells (HLWECs) and human umbilical vein endothelial cells (HUVECs) after stimulation by interleukin(IL)-1beta. In an HLMEC-conditioned medium, large amounts of total (single and 2-chain) HGF were detected, and were 26- to 28-fold higher than those in HUVECs or human lung fibroblasts. The production of total HGF increased in a dose-dependent manner (4.7 to 9.2 times) with IL-1beta. In contrast, the amount of HGF in an HUVEC-conditioned medium was unaffected by IL-1beta treatment. The amount of cell-associated HGF also showed a dose-related increase (140% to 160%) in HLMECs, but not in HUVECs with IL1beta. In addition, HGF and c-met (HGF receptor) mRNAs in HLMECs and HUVECs were examined by the RT-PCR method. HGF and c-met mRNAs were clearly detected in HLMECs before and after treatment with IL-1beta, but not in HUVECs. These results suggest that increases in HGF production from HLMECs may play a role in the reconstruction process following inflammatory damage in lung tissue.

We have studied the growth mechanism of a Pd(100)-p(2×2)-p4g-Al surface alloy by scanning tunneling microscopy (STM). The surface alloy has a bilayer structure and is formed by annealing at 450–700 K (depending on the initial aluminum coverage) after the deposition of aluminum on Pd(100) at room temperature. The ratio of the surface-alloy coverage to the initial aluminum coverage is found to be constant (0.44) irrespective of the initial aluminum coverage from ∼0.5 monolayers (ML) up to ∼2 ML. The growth mechanism of the surface alloy is proposed on the basis of the STM measurements at various annealing temperatures. Upon annealing at 450 K, some of the surface aluminum atoms migrate into the bulk and, instead, palladium atoms come out to the surface. These palladium atoms react with aluminum atoms remaining on the surface to form a surface alloy. When the initial aluminum coverage is less than 1 ML, bilayer-high islands of the surface alloy with an average area of ∼100 nm 2 are formed at 450–500 K, which diffuse on the terrace at 500–700 K and coalesce to form larger islands. A possible role of the percolation transition of aluminum islands in the formation of the surface alloy is discussed.

In rodents, placental lactogen (PL)-I is considered to be the first trigger to enhance pancreatic islet B-cell function, and after its secretion is diminished at mid-pregnancy, PL-II takes over this role. However, little information is available on the regulation of islet B-cell function and proliferation by lactogenic hormones during the last third of pregnancy. This was the focus of the present study using rats in which pregnancy was forcibly prolonged. This rat possesses unique characteristics in that PL-I is re-secreted during the prolonged period of pregnancy and the peak concentrations in maternal circulation are comparable with those observed during mid-pregnancy in normal-pregnancy rats. Pregnancy was prolonged by successive administration of pregnant mare's serum gonadotropin (30IU/rat, s.c. on day 12) and human chorionic gonadotropin (10IU/rat, i.v. on day 14). When the insulin secretory responses to 10mmol/l glucose in islets obtained from normal-pregnancy and prolonged-pregnancy rats were tested, each insulin secretory response correlated well with the values of plasma lactogenic activity throughout the period of pregnancy and lactation. Examination of B-cell proliferation in normal-pregnancy rats showed that 5-bromo-2'-deoxyuridine (BrdU) incorporation into dividing B-cells reached a maximum on day 15 and then decreased markedly towards term. No increase in B-cell proliferation was observed on day 19 when plasma lactogenic activity reached the maximum. In prolonged-pregnancy rats, BrdU incorporation also continued to decrease as observed in normal-pregnancy rats after day 15, and then no enhancement in B-cell proliferation was observed even when the plasma lactogenic activity, including re-secreted PL-I, reached maximum. These results suggest that, in the last third of pregnancy, B-cell proliferation is no longer stimulated by lactogenic hormones in contrast to the insulin secretory response which is sustained.

OBJECTIVE: We studied whether increased urinary transferrin excretion rates (TERs) (urinary transferrin-to-urinary creatinine ratio > or = 107 micrograms/mmol, which is the sum of an average and 2 SDs in 431 healthy nondiabetic individuals) would predict the development of microalbuminuria (urinary albumin-to-urinary creatinine ratio > or = 2.8 mg/mmol) in patients with type 2 diabetes and normal urinary albumin excretion rates (AERs) (albumin-to-creatinine ratio < 2.8 mg/mmol). We also studied the influence of blood pressure, glycemic control, and serum levels of lipids and apolipoproteins on the later development of microalbuminuria. RESEARCH DESIGN AND METHODS: In 77 diabetic patients with normal AER, AER and TER were measured at baseline and after 24 months of follow-up. Blood pressure, glycemic control, and serum levels of lipids and apolipoproteins were measured at 1- to 2-month intervals during the follow-up period. RESULTS: Of the 16 patients who initially had increased TER, 5 (31%) developed microalbuminuria. In contrast, of the 61 who initially had normal TER, 4 (7%) developed microalbuminuria (P = 0.016). At baseline, no difference was found in age, sex, diabetes duration, diabetic medications, prevalence of hypertension, blood pressure, HbA1c levels, or serum lipid and apolipoprotein concentrations between the two group of patients with normal and increased TER. There was also no difference in duration of hypertension and prevalence of users of ACE inhibitors between two subgroups of hypertensive patients with normal and increased TER. During the 24 month follow-up period, those whose condition progressed to microalbuminuria had increased serum levels of triglycerides (1.87 +/- 0.49 vs. 1.29 +/- 0.64 mmol/l, P = 0.003) and apolipoprotein B (114 +/- 20 vs. 102 +/- 24 mg/dl, P = 0.05) and tended to have increased HbA1c levels (7.7 +/- 1.0 vs. 7.1 +/- 1.1%, P = 0.10) compared with those in whom microalbuminuria did not develop. Blood pressure, however, did not differ. In multivariate stepwise logistic regression analysis, the association between increased TER at baseline and subsequent development of microalbuminuria was significant (odds ratio 7.04 [95% CI 1.02-48.5], P = 0.04). CONCLUSIONS: In patients with type 2 diabetes and normal AER, increased TER may predict the development of microalbuminuria and abnormalities in triglyceride-rich lipoprotein metabolism, and poor glycemic control may be associated with this progression.

Atomic structure and hydrogen adsorption on the Pd(100)-p(2×2)-p4g–Al surface alloy have been studied using scanning tunneling microscopy and electron energy loss spectroscopy. It was found that the topmost layer of this surface alloy is reconstructed into the p(2×2)-p4g structure, which is in good agreement with the recent crystallographic results based on low-energy electron diffraction and ion scattering. The initial hydrogen adsorption on this surface alloy gives rise to an unusual desorption peak, which does not shift with increasing coverage as reported previously. The vibrational spectrum for adsorbed hydrogen corresponding to this desorption state shows a peak at 77 meV, which is assigned to H at four-fold hollow sites on the clock-reconstructed p(2×2)-p4g–Pd layer.

Ammonium sulfide combined etching (ACE) is a treatment carried out prior to metalorganic vapor phase epitaxy (MOVPE) regrowth of InP on a surface processed by methane/hydrogen (CH 4 /H 2 )-reactive ion etching (RIE). It involves dipping a sample in ammonium sulfide (NH 4 S x ) solution and subsequently treating it with sulfuric acid (H 2 SO 4 ). ACE can improve the electrical properties of the processed surface and remove impurities, such as oxygen and carbon, at the interface regrown on the processed surface. Regarding the ACE mechanism, the NH 4 S x treatment appears to change the surface from a condition where surface oxide cannot be removed by H 2 SO 4 into one where it can be by H 2 SO 4 .

Purpose/Objectives: Substantial cervical body volume reduction (CBVR) occurs during fractionated external beam radiation therapy (EBRT) for head-and-neck cancer (HNC) and could have potential dosimetric influences. This study aims to investigate measurable clinical factors before treatment initiation correlating with CBVR during curative EBRT in HNC patients, and to determine which patients receive the great benefit from routine adaptive radiation therapy (ART). Materials/Methods: Fifty-six patients with oropharyngeal squamous cell carcinoma (OSCC) and 67 patients with hypopharyngeal squamous cell carcinoma (HSCC) had received curative EBRT between 2006 and 2013 were enrolled. For EBRT planning, computed tomography (CT) images were acquired before EBRT initiation and between two to seven weeks after the start of EBRT for replanning in each patient. A MATLAB program was used to evaluate the CBVR rate (CBVRR) between the initial and replanning CT imaging. The following factors were assessed for correlation with CBVRR: the T and N stage, induction and concurrent chemotherapy, the initial gross tumor volume (GTV), the GTV reduction rate (GTVRR) between the initial and replanning CT imaging, the initial body weight (BW) and the BW loss rate (BWLR) during the EBRT course. Results: In the OSCC group, the CBVRR ranged from 1.8 to 17.1% (median, 6.8%). In the HSCC group, the CBVRR ranged from 1.2 to 23.7% (median, 6.5%). In non-parametric univariate analysis, the N3 stage demonstrated a greater trend with the CBVRR than the N2c≥ stage in the HSCC group (p=0.023), whereas marginal inclination (p=0.096) was found in the OSCC group. The CBVRR was substantially related to the GTVRR (p=0.001) in the HSCC group.

The continuous annealing line No. 2 (2 KAP) started running commercially in May 1992 to produce high quality steel sheets. In order to meet customer demand and improve sheet quality, not only conventional quality assurance devices but also newly developed ones, such as on-line Lankford value monitoring systems, new radiation thermometer, ultrasonic testing systems and surface inspection systems, were installed.

CBN grinding wheels are increasingly used on a wide range of engineering materials. This paper compares the grinding performance of monocrystalline (M-CBN) and polycrystalline (P-CBN) abrasives with a newly developed nanocrystalline (N-CBN) abrasive, when grinding nickel-based superalloys. The N-CBN grits possess average crystal grain diameters less than 1 μm compared to average primary grain diameters of 2.3 μm for P-CBN. It was found that the nanocrystalline CBN grits possess higher fracture strength which give reduced wear rates and yield an order of magnitude increase in grinding wheel life. Analysis of the cutting edge distribution shows that the reduced wear rate of N-CBN is due to the predominance of a micro-fracturing mode of abrasive wear. The size of this micro-fracturing is considerably smaller in N-CBN than in P-CBN.

The electrical properties of the (100) InP surface were studied based on the fabrication process of a buried heterostructure (BH) laser diode (LD). The current-voltage (I- V) and capacitance-voltage (C- V) characteristics were measured for Schottky barriers on the surface at each step of the process. The characteristic variation during the process showed the C2H6/H2-reactive ion etching (RIE) induced damage on the near-surface region: a layer resulting from phosphorus desorption, a low p-concentration layer due to hydrogen passivation, and deep donor defects with electrical drift phenomena. It was found that the damage layers were removed by annealing after the chemical etching which produced almost the same surface as that immediately before the BH regrowth.

The present study investigated the effect of rat placental lactogen-II (rPL-II) on insulin secretion and B-cell proliferation of the maternal islets during the last half of pregnancy in rats using a homologous system. Pancreatic islets were isolated from nonpregnant rats and rats at day 13 of pregnancy and cultured for 8 days in medium containing trophoblast culture medium or purified hormones. The medium was changed daily and insulin concentrations were determined by measuring immunoreactivity. The number of proliferating B cells were determined by double staining for both insulin and 5'-bromo-2'-deoxyuridine (BrdU) incorporated into replicating DNA during the last 24 h of incubation. rPL-II-enriched medium, in which trophoblasts of placentae from rats at day 13 of pregnancy were incubated for 8 days, was added to the islet culture system. Insulin concentration in the medium of non-pregnant rat islets was significantly increased and doubled on incubation in 100% trophoblast culture medium. Addition of purified rPL-II to the culture medium of pregnant rat islets stimulated insulin secretion at the concentrations of 50-500 ng ml-1 in a dose-dependent manner. The stimulatory effect of rPL-II on insulin secretion was found to be more than double that with rat prolactin (rPRL) and rat growth hormone (rGH) at 100 ng ml-1. For determination of B-cell proliferation, non-pregnant rat islets were incubated with rPL-II, rPRL or rGH at 1000 ng ml-1 for 8 days and then 10 mmol BrdU l-1 was added during the last 24 h of incubation. rPL-II (5.30 +/- 0.36%), rPRL (3.79 +/- 0.34%) and rGH (2.87 +/- 0.29%) significantly increased the rate of incorporation of BrdU into the B cells compared with that of the control (1.34 +/- 0.18%). These results indicate that rPL-II directly regulates insulin secretion and B-cell proliferation of maternal islets during the last half of pregnancy in rats.

We clarified the degradation behavior of semi-insulating buried heterostructure lasers in which mesa structures were fabricated by RIE and then buried by MOVPE. The degradation rate and mode correlated with the quality of the BH interface. Based on the correlation, a condition for highly stable SIBH lasers was demonstrated and confirmed experimentally and statistically.

The poorly differentiated human gastric carcinoma cell line MKN-45 possesses histamine H2 receptors which are homologously desensitized by histamine. In order to clone the cDNA of a receptor kinase specific for H2 receptors, we performed RT-PCR at a low annealing temperature using oligo-DNA primers bearing the conserved sequences of the kinase domain of the G protein-coupled receptor kinase (GRK) family. However, we were able to isolate only cDNAs for beta-adrenergic receptor kinase 1 (beta ARK1) and GRK6. Interestingly, treatment of MKN-45 cells with beta ARK1 antisense phosphorothioate oligo-DNA (PON) resulted in significant loss of desensitization of H2 receptors by histamine, whereas GRK6 antisense PON had no effect. Thus, beta ARK1 appears to be involved in the homologous desensitization of H2 receptors in MKN-45 cells.

A series of site-directed mutants, E35Q, E39Q, and E35Q-D179N, in the gene encoding manganese peroxidase isozyme 1 (mnp1) from Phanerochaete chrysosporium, was created by overlap extension, using the polymerase chain reaction. The mutant genes were expressed in P. chrysosporium during primary metabolic growth under the control of the glyceraldehyde-3-phosphate dehydrogenase promoter. The mutant manganese peroxidases (MnPs) were purified and characterized. The molecular masses of the mutant proteins, as well as UV-vis spectral features of their oxidized states, were very similar to those of the wild-type enzyme. Resonance Raman spectral results indicated that the heme environment of the mutant MnP proteins also was similar to that of the wild-type protein. Steady-state kinetic analyses of the E35Q and E39Q mutant MnPs yielded K(m) values for the substrate MnII that were approximately 50-fold greater than the corresponding K(m) value for the wild-type enzyme. Likewise, the kcat values for MnII oxidation were approximately 300-fold lower than that for wild-type MnP. With the E35Q-D179N double mutant, the K(m) value for MnII was approximately 120-fold greater, and the kcat value was approximately 1000-fold less than that for the wild-type MnP1. Transient-state kinetic analysis of the reduction of MnP compound II by MnII allowed the determination of the equilibrium dissociation constants (KD) and first- order rate constants for the mutant proteins. The KD values were approximately 100-fold higher for the single mutants and approximately 200-fold higher for the double mutant, as compared with the wild-type enzyme. The first-order rate constants for the single and double mutants were approximately 200-fold and approximately 4000-fold less, respectively, than that of the wild-type enzyme. In contrast, the K(m) values for H2O2 and the rates of compound I formation were similar for the mutant and wild-type MnPs. The second-order rate constants for p-cresol and ferrocyanide reduction of the mutant compounds II also were similar to those of the wild-type enzyme.

Most anemic patients with chronic renal failure have gastric mucosal lesions. However, these gastric lesions are often improved after the administration of recombinant human erythropoietin (rHuEPO). We have used the rat gastric mucosal cell line RGM-1, to examine the possibility that rHuEPO might directly stimulate the growth of gastric mucosal cells in vitro. Our results show that rHuEPO dose-dependently increased [3H]thymidine incorporation into RGM-1 cells and their expression of c-myc gene. In addition, 125I-rHuEPO specifically bound to RGM-1 cells, and moreover, erythropoietin receptor gene expression was detected by RT-PCR. We conclude that rHuEPO has a direct growth-promoting effect on RGM-1 cells, suggesting possible usefulness of rHuEPO administration for the treatment of gastric mucosal damage in patients with chronic renal failure.

RGM-1 is an epithelial cell line established from gastric mucosa of adult Wistar rats. In this study, we characterized this newly established cell line by Northern blot analysis. We also investigated deoxyribonucleic acid (DNA) synthesis and hexosamine production in RGM-1 by PGE2. Northern blot analysis did not detect any transcript of proton pump, gastrin receptor, histidine decarboxylase, somatostatin and pepsinogen 1, indicating the absence of characteristics of parietal, ECL, D and chief cells in RGM-1 cells. However, this periodic acid-Schiff (PAS)-positive cell line expressed prostaglandin EP4 receptor mRNA but not EP1 and EP3 receptor mRNAs. [3H]-thymidine incorporation into DNA of the cells was not increased by PGE2. In contrast, PGE2 increased hexosamine content in RGM-1 cells. These results suggest that RGM-1 may be a useful model of gastric mucosal cells and that PGE2 plays a role on mucin synthesis in RGM-1 cells possibly via EP4 receptors.

Ventilation imaging can be performed using thoracic four dimensional computed tomography (4D-CT) images (max inhale phase and max exhale phase) and deformable image registration (DIR). If this method was administered in multi institution, some institution would use commercially available automatic DIR software. But, there are not many reports about commercially available automatic DIR. In this study, we evaluated the accuracy of a commercially available automatic deformable image registration (DIR) algorithm using 4D-CT images. For evaluating the accuracy of DIR, registration error was calculated by difference between manual displacement and automatic calculated displacement (DIR outputs). A B-spline DIR algorithm implemented in a Velocity AI ver. 2.7.0 software (Velocity Medial, GA, USA) was evaluated. 4D-CT images including 300 landmarks /case, throughout the lung, provided by DIR-lab (www.dir-lab.com). In this study, five patients were studied. The goal of DIR was to find a point to point correspondence between inhale image and exhale image. First, manual displacement was calculated by land mark points between max inhale phase and max exhale phase. Next, DIR outputs were calculated by a Velocity AI. After that, registration error was calculated by difference between manual displacement and DIR outputs. The mean 3D registration error (standard deviation) for the five cases was 2.70 (2.24) mm. Fewer large errors were seen, but the frequent histogram had a peak at 1.5mm of 3D error, and the frequencies decline as one moves away from the peak. The average 3D registration errors for case1 were 0.94 mm for 1.5 mm motion distance magnitude, 1.96 mm for 6.0 mm and 3.70 mm for 9.0 mm, respectively. Our result clearly shows that the accuracy of DIR in Velocity AI was within 3.0 mm. Therefore commercially available automatic DIR may be useful for image-guided radiation therapy, adaptive radiation therapy and ventilation imaging.

We evaluated dose calculation accuracy for modi- fied Cone-Beam computed tomography (CBCT) images using Multi -level-threshold algorithm, and compared it with un- modified CBCT images. Inhomogeneous pelvis phantom imag- es and three prostate cancer patient images were acquired from both planning CT (PCT) and CBCT. The Hounsfield Units (HUs) were measured for air, tissue, bone. Using in- house software, three different tissue types were differentiated in both imaging modalities. The HUs of CBCT images were replaced by the mean HUs of the same tissue type of the PCT. An intensity modulated radiation therapy (IMRT) plan was created on PCT and copied to the modified CBCT. To evaluate the dosimetric accuracy, dose distributions based on CBCT images were compared it with PCT for four datasets (one inhomogeneous phantom, three prostate cancer patients ). HU- ED calibration acquired with PCT was used in both images. In the inhomogeneous pelvis phantom, differences in dose param- eter were seen. Regarding PTV, Rectum, and Bladder, differ- ences in mean dose between PCT and CBCT were 0.4%, 0.4%, and 0.1%, respectively, whereas those between PCT and modi- fied CBCT were 0.2%, 0.1%, and 0%, respectively. In the patient study, the average dose difference of PTV, Rectum, and Bladder between PCT and CBCT were 1.0%, 0.2%, and 0.6%, respectively, compared to PCT and modified CBCT, 0.5%, 0.1%, and 0.2%, respectively. We found that the dose difference in the plans based on PCT and CBCT were de- creased after this modification. The uncertainty in patient positioning between PCT and CBCT may cause additional discrepancies in the calculated results compared to the results in the phantom study. An accurate dose calculation based on CBCT images is possible when density distributions are cor- rected. This method does not need to acquire HU-ED calibra- tion for CBCT, and may be able to remove scatter.

Objective: We investigated the effects of partial volume and respiratory motion using a National Electrical Manufacturers Association (NEMA) phantom and proposed a simple method for correction of maximum standardized uptake value (SUVmax) for respiratory motion in early lung cancer. Methods: The maximum recovery coefficient (RC) in static mode were measured using the NEMA phantom and a dynamic moving platform. The phantom on the platform was either at rest or moving sinusoidally along the longitudinal axis of the scanner to simulate respiratory motion. We also calculated estimated RC using our approximation. Results: RC of the sphere of 28mm in diameter decreased from 0.96 to 0.80 and 0.41 with 20 and 50 mm of motion amplitude, respectively. For the sphere of 10 mm in diameter, RC was decreased from 0.40 to 0.18 and 0.08 with 20 and 50 mm of motion amplitude, respectively. Our results showed that RC decreased with increase in motion amplitude. Average percentage differences between measurement and estimation in the sphere of 37, 28, 22, 17, 13 and 10 mm were -1.8 ± 3.7, -3.1 ± 11.3, -2.8 ± 10.5, -8.1 ± 6.6, -7.0 ± 12.3 and -1.8 ± 12.2 %, respectively. This result showed that our simple correction method could estimate SUVmax with moderate accuracy. Conclusions: Our results clearly demonstrated that RC decreases with increase in motion amplitude, as expected. Our simple correction with moderate accuracy method could not precisely estimate RC. However, the estimated values agreed with the measurements. Thus, our methods could be used in clinical practice to calculate the approximate SUVmax for lung cancer patients undergoing radiotherapy showing the malignancy grading for early lung cancer.

Complement-dependent activation of immune cells is regulated by cell surface membrane receptors. In this study, expression of complement receptors (CR) on human blood basophils (n = 11), tissue mast cells (lung, n = 7; skin, n = 10; uterus, n = 4; tonsil, n = 3; heart, n = 10), and on respective human cell lines (basophil line KU-812, mast cell line HMC-1) was analyzed by the use of mAbs and indirect immunofluorescence. Normal blood basophils and KU-812 cells were found to express C5aR (CD88), membrane cofactor protein (CD46), decay-accelerating factor (CD55), and membrane attack complex inhibitory factor (CD59), as well as the previously recognized CR1 (CD35), CR3 alpha (CD11b), CR4 alpha (CD11c), and CR3/4 beta (CD18). Mast cells from all organs as well as HMC-1 cells expressed CD46, CD55, and CD59, but not CD11b, CD21, or CD35. The C5aR (CD88) was detectable on skin mast cells, a subset (5 to 15%) of cardiac mast cells, and on HMC-1 cells, but not on lung, uterus, or tonsillar mast cells (< 5%). Moreover, double immunoperoxidase staining (tryptase vs C5aR/CD88) revealed in situ expression of C5aR on skin, but not lung mast cells. Recombinant human (rh) C5a, at 10(-10) to 10(-7) M, induced secretion of histamine from basophils (rhC5a, 10(-8) M: 53.4 +/- 3.1% vs control < 5%) and from skin mast cells (rhC5a, 10(-8) M: 25.8 +/- 16.1% vs control < 10% histamine release), but not from other mast cells (rhC5a or control: < 10%, p > 0.05). The rhC5a-induced secretion of histamine from basophils and skin mast cells was inhibited by S5/1, a blocking Ab against CD88 (basophils: 37.2% to 75.1%; skin mast cells: 39.2% to 83.9% inhibition, p < 0.05). Together, this study shows that a) basophils and mast cells express a different profile of complement receptors, b) C5a-dependent mediator release in skin mast cells and basophils is mediated via CD88, and c) mast cells constitute a heterogeneous lineage in terms of expression of the C5a binding site CD88.