In this letter, we present a structured Kalman filter associated with the transformation matrix for observable Kalman canonical decomposition from conventional Kalman filter (CKF) in order to ...generate a more accurate time scale. The conventional Kalman filter is a special case of the proposed structured Kalman filter which yields the same predicted unobservable or observable states when some conditions are satisfied. We consider an optimization problem respective to the transformation matrix where the objective function is associated with not only the expected value of prediction error but also its variance. We reveal that such an objective function is a convex function and show some conditions under which CKF is nothing but the optimal algorithm if ideal computation is possible without computation error. A numerical example is presented to show the robustness of the proposed method in terms of the initial error covariance.
As a dielectric composite material which can serve as a candidate film capacitor, a polyvinylidene fluoride (PVDF)-based composite film embedded with n-dodecylammonium-modified montmorillonite ...(12CH3-MMT) was investigated. 12CH3-MMT was first synthesized by an ion exchange method, and it was delaminated into a single to several ten layers by stirring in a PVDF/N,N-dimethylformamide solution at 65 °C for 4 days. The resultant 12CH3-MMT/PVDF composite film exhibited higher breakdown strength (Ebd) than a pure PVDF film, and Ebd increased as the amount of 12CH3-MMT in the composite film increased up to 10.0 wt %, which was consistent with the prediction based on a simplified physical simulation. The increase in the amount of 12CH3-MMT more than 10.0 wt % lead to the decrease in Ebd contrary to the prediction, which could be attributed to the mutual contact of 12CH3-MMT fillers in the composite by TEM observation. It was found that 12CH3-MMT were homogeneously dispersed in PVDF with a wide range of amount up to 10.0 wt %, and that the 12CH3-MMT/PVDF composite film with higher energy density than a biaxially oriented polypropylene were obtained.
The PI3K (phosphatidylinositol-3-kinase)/mTOR (mammalian target of rapamycin) pathway is frequently activated in endometrial cancer through various PI3K/AKT-activating genetic alterations. We ...examined the antitumor effect of NVP-BEZ235--a dual PI3K/mTOR inhibitor--and RAD001--an mTOR inhibitor--in 13 endometrial cancer cell lines, all of which possess one or more alterations in PTEN, PIK3CA, and K-Ras. We also combined these compounds with a MAPK pathway inhibitor (PD98059 or UO126) in cell lines with K-Ras alterations (mutations or amplification). PTEN mutant cell lines without K-Ras alterations (n = 9) were more sensitive to both RAD001 and NVP-BEZ235 than were cell lines with K-Ras alterations (n = 4). Dose-dependent growth suppression was more drastically induced by NVP-BEZ235 than by RAD001 in the sensitive cell lines. G1 arrest was induced by NVP-BEZ235 in a dose-dependent manner. We observed in vivo antitumor activity of both RAD001 and NVP-BEZ235 in nude mice. The presence of a MEK inhibitor, PD98059 or UO126, sensitized the K-Ras mutant cells to NVP-BEZ235. Robust growth suppression by NVP-BEZ235 suggests that a dual PI3K/mTOR inhibitor is a promising therapeutic for endometrial carcinomas. Our data suggest that mutational statuses of PTEN and K-Ras might be useful predictors of sensitivity to NVP-BEZ235 in certain endometrial carcinomas.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and aim
Achalasia is a disease characterized by inadequate relaxation of the lower esophageal sphincter (LES) and impaired peristalsis, for which esophageal motor function testing is ...essential in making a definitive diagnosis. However, the diffusion rate of esophageal pressure testing in Japan is low. We, therefore, examined whether achalasia could be identified by esophageal clearance testing with low-density barium (Timed Barium Esophagogram: TBE).
Materials and methods
126 cases (62 males, median age of 46 years), excluding those who had not undergone TBE during their initial laparoscopic Heller-Dor surgery, were chosen as the subjects from among those who were diagnosed with achalasia from November 2012 when HRM was introduced. The type of dilation, maximum esophageal transverse diameter, and esophageal clearance measurements by TBE were retrospectively examined. With respect to TBE, 200 mL of 45 weight% low-density barium was ingested as quickly as possible, after which the barium column heights (
H
0,
H
1,
H
2, and
H
5) were measured 1 min, 2 min, and 5 min following ingestion.
Results
The types of dilation indicated included: straight type (105 cases, 83%); sigmoid type (20 cases, 16%); and advanced sigmoid type (1 case, 1%). The maximum transverse diameter of the esophagus was 45 (34–54) mm, with Grade I (
d
< 30 mm) in 33 cases, Grade II (35 mm <
d
< 60 mm) in 75 cases, and Grade III (
d
< 60 mm) in 18 cases. The values for H0, H1, H2, and H5 were 162 (117–201) mm, 142 (98–199) mm, 130 (94–183) mm, and 119 (77–178) mm, respectively. 114 cases (90.5%) were not cleared after 5 min, while 12 cases (9.5%) were cleared by 5 min later (
H
1 = 0 +
H
2 = 0 +
H
5 = 0) and 7 cases (5.6%) by 2 min later (
H
1 = 0 +
H
2 = 0), with only 6 cases (4.8%) having complete clearance within 1 min (
H
1 = 0). Moreover, the degree of dilatation in patients with complete clearance within 1 min was three patients (2.4%) each for Grade I and Grade II, respectively.
Conclusions
Approximately 2.4% of achalasia cases had mostly normal esophageal clearance and no esophageal dilation. Based on the state of esophageal clearance by TBE and the maximum transverse diameter of the esophagus, it seems by and large possible to identify achalasia cases.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Photoimmunotherapy (PIT) is a promising tumor-selective treatment method that uses light-absorbing dye-conjugated antibodies and light irradiation. It has been reported that IR700 fluorescence ...changes with light irradiation. The purpose of this study was to investigate the fluorescence intensity and antitumor effect of PIT using real-time fluorescence observation of tumors and predict the required irradiation dose. The near-infrared camera system LIGHTVISION was used to image IR700 during PIT treatment. IR700 showed a sharp decrease in fluorescence intensity in the early stage of treatment and almost reached a plateau at an irradiation dose of 40 J/cm. Cetuximab-PIT for A431 xenografts was performed at multiple doses from 0-100 J/cm. A significant antitumor effect was observed at 40 J/cm compared to no irradiation, and there was no significant difference between 40 J/cm and 100 J/cm. These results suggest that the rate of decay of the tumor fluorescence intensity correlates with the antitumor effect by real-time fluorescence imaging during PIT. In addition, when the fluorescence intensity of the tumor plateaued in real-time fluorescence imaging, it was assumed that the laser dose was necessary for treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
Chest pain reduces the quality of life of patients with achalasia. Although laparoscopic Heller-Dor surgery (LHD) is a standard surgical treatment for achalasia, its therapeutic efficacy ...for chest pain is not clear. The present study evaluated the therapeutic efficacy of LHD for chest pain and tried to identify factors associated with the relief of chest pain.
Methods
The study included 244 patients with preoperative chest pain who underwent LHD as the first surgical intervention. The questionnaire-based symptom frequency score was multiplied by the severity score, and the calculated metric was defined as the symptom score. The study population was stratified, by the change in the chest pain symptom score, into Complete Remission (CR), Partial Remission (PR), and No Remission (NR) groups, which were compared for patient background and surgical outcome. Multivariate analysis was also performed to determine factors associated with the relief of chest pain.
Results
As for preoperative clinicopathological conditions, the CR subgroup was older (
p
= 0.0169) with fewer previous balloon dilatations (
p
= 0.009). Although no difference was detected in the surgical outcome, the NR group had higher postoperative symptom scores for both difficulty in swallowing and vomiting and a lower score for patient satisfaction with surgery (
p
= 0.0141). Multivariate analysis detected two factors associated with CR: disease duration over 60 months and less than two previous balloon dilatations.
Conclusions
LHD improved chest pain symptoms in 90% of patients with achalasia. The patients who achieved relief of chest pain were characterized by disease duration over 60 months and less than two previous balloon dilatations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims/Introduction
Dipeptidyl peptidase‐4 inhibitors are used for treatment of patients with type 2 diabetes. In addition to glycemic control, these agents showed beneficial effects on lipid ...metabolism in clinical trials. However, the mechanism underlying the lipid‐lowering effect of dipeptidyl peptidase‐4 inhibitors remains unclear. Here, we investigated the lipid‐lowering efficacy of anagliptin in a hyperlipidemic animal model, and examined the mechanism of action.
Materials and Methods
Male low‐density lipoprotein receptor‐deficient mice were administered 0.3% anagliptin in their diet. Plasma lipid levels were assayed and lipoprotein profile was analyzed using high‐performance liquid chromatography. Hepatic gene expression was examined by deoxyribonucleic acid microarray and quantitative polymerase chain reaction analyses. Sterol regulatory element‐binding protein transactivation assay was carried out in vitro.
Results
Anagliptin treatment significantly decreased the plasma total cholesterol (14% reduction, P < 0.01) and triglyceride levels (27% reduction, P < 0.01). Both low‐density lipoprotein cholesterol and very low‐density lipoprotein cholesterol were also decreased significantly by anagliptin treatment. Sterol regulatory element‐binding protein‐2 messenger ribonucleic acid expression level was significantly decreased at night in anagliptin‐treated mice (15% reduction, P < 0.05). Anagliptin significantly suppressed sterol regulatory element‐binding protein activity in HepG2 cells (21% decrease, P < 0.001).
Conclusions
The results presented here showed that the dipeptidyl peptidase‐4 inhibitor, anagliptin, exhibited a lipid‐lowering effect in a hyperlipidemic animal model, and suggested that the downregulation of hepatic lipid synthesis was involved in the effect. Anagliptin might have beneficial effects on lipid metabolism in addition to a glucose‐lowering effect.
The results presented here indicated that the DPP‐4 inhibitor, anagliptin, exhibited a lipid‐lowering effect in LDLR‐deficient mice as a hyperlipidemic animal model, and suggested that the downregulation of hepatic lipid synthesis was involved in the effect.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
The forced swim test (FST) is a screening model for antidepressant activity; it causes immobility and induces oxidative stress. We previously reported that radon inhalation has ...antidepressant-like effects in mice potentially through the activation of antioxidative functions upon radon inhalation. This study aimed to investigate the effect of prior and post low-dose X-irradiation (0.1, 0.5, 1.0 and 2.0 Gy) on FST-induced immobility and oxidative stress in the mouse brain, and the differences, if any, between the two. Mice received X-irradiation before or after the FST repeatedly for 5 days. In the post-FST-irradiated group, an additional FST was conducted 4 h after the last irradiation. Consequently, animals receiving prior X-irradiation (0.1 Gy) had better mobility outcomes than sham-irradiated mice; however, their levels of lipid peroxide (LPO), an oxidative stress marker, remained unchanged. However, animals that received post-FST X-irradiation (0.5 Gy) had better mobility outcomes and their LPO levels were significantly lower than those of the sham-irradiated mice. The present results indicate that 0.5 Gy X-irradiation after FST inhibits FST-induced immobility and oxidative stress in mice.
Although graft failure (GF) is a fatal complication after allogeneic stem cell transplantation (SCT), no mortality risk assessments after salvage SCT have been reported. We developed a comprehensive ...prognostic scoring system consisting of patient and comorbidity factors with 470 patients as a training cohort out of 940; these patients underwent salvage SCT for GF. The multivariate analysis demonstrated that older age, poorer performance status, a continuation of antimicrobial treatment, and severe organ dysfunction were independently associated with worse overall survival (OS) and non-relapse mortality (NRM). Based on each factor's hazard ratio, weighted scores of 1-3 were assigned to these factors. Using the summed scores (0-8), a prognostic scoring system successfully stratified outcomes after salvage SCT in the cohort. For patients in the low (0-2, n = 122), intermediate (3-4, n = 209), and high score (5-8, n = 110) groups, the 1-year OS was 62.8%, 40.8%, and 14.2%, respectively (P < 0.001), whereas the 1-year NRM was 24.1%, 43.9%, and 72.7%, respectively (P < 0.001). The prognostic value of the scoring system was confirmed in the validation cohort (n = 470). Our scoring system is useful for predicting survival after salvage SCT.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and aim
The relationship between gastroesophageal reflux disease (GERD) and sleep disturbance has recently been pointed out and is garnering substantial attention. Although there are ...reports that point out the effectiveness of medical treatment for sleep disturbance associated with GERD, examinations of the pathological condition, including reflux during sleep, are inadequate. In the present study, we evaluated the recumbent reflux in patients with GERD and sleep disturbance using multichannel intraluminal impedance pH (MII-pH), and attempted to suppress recumbent reflux by surgical treatment to examine the pathophysiology of patients with GERD and sleep disturbance.
Materials and methods
Of the 47 patients with GERD-related diseases in whom laparoscopic fundoplication was performed at The Jikei University Hospital from January 2016 to June 2017, 31 patients (average age: 55.9 ± 13.8 years, male in 25), excluding 9 with surgical indications only for esophageal hiatal hernia and 7 without postoperative evaluation, were the subjects of this study. All surgical procedures were performed by the Toupet method. We used the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep disturbance, setting 5.5 as the cut-off value, based on the report by Doi et al., with any conditions beyond this value deemed sleep disturbance. The evaluation of gastroesophageal reflux was carried based on the MII-pH using the Sleuth, manufactured by Sandhill Corporation, with an automatic analysis carried out by computer. Furthermore, recumbent abnormal reflux was defined as recumbent all reflux (times) > 7. All evaluations were performed preoperatively and at 3 months after the operation. The data were expressed in medians and interquartile ranges, with
p
< 0.05 defined as statistically significant by the Mann–Whitney, Wilcoxon, or Chi-squared test.
Results
Although sleep disturbance was found in 19 cases (61%), 8 (42%) of which were actually confirmed as nighttime abnormal reflux, of whom 5 cases (63%) showed significant improvement in their sleep disturbance following the operation, with a PSQI score of lower than 5.5. Among these 5 cases, postoperative recumbent abnormal reflux was also significantly reduced as compared with the preoperative condition (17 vs. 2 times/day,
p
= 0.042). Furthermore, sleep disturbance improved and recumbent abnormal reflux also decreased in two cases, with sleep disturbance improved by controlling the nighttime reflux via surgery in a total of 7 cases (87.5%). Although the PSQI score was as high as 14 points before and after the operation in one case, the rate of recumbent abnormal reflux was remarkably reduced, with sleep disturbance and recumbent reflux considered irrelevant. Furthermore, regarding the frequency of recumbent acid/non-acid reflux, while non-acid reflux was significantly more frequent in the patients with recumbent reflux complications (9 vs. 1 time/day,
p
< 0.001), there was no marked difference in the frequency of acid reflux.
Conclusions
Among cases with GERD and sleep disturbance, approximately one-third of them showed findings suggestive of the involvement of recumbent reflux in sleep disturbance, with reflux characterized by non-acid reflux.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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