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In this paper, a new finite element model updating (FEMU) method is proposed based on mixed-integer nonlinear programming (MINLP) to deal with model-form uncertainty in FE models. Depending on modelers’ preference and experience, various FE models can be constructed for a specific structure in practice. However, no one can guarantee that a specific model representation is always best (Model-form uncertainty). Conventional method should perform model updating for each FE model independently and select a best one among them, so that it becomes computationally intensive with many candidate FE models. To handle model-form uncertainty, this study formulates FEMU as the MINLP problem. The proposed method assigns an integer variable for model choice, while continuous real variables are used for the updating parameters. With this formulation, the optimization algorithm can explore both model and parameter space simultaneously to deal with the model-form uncertainty in FE models. Firstly, three numerical experiments were explored to evaluate the performance of the proposed method by considering possible situations in reality as follows: (1) a true FE model exists in model space with an admissible FE model; (2) only admissible FE model exists in model space; and (3) no true and admissible FE models exist in model space. Then, the proposed method was experimentally validated through a real bridge. The results show that the proposed method can find a best FE model with optimal estimates of the updating parameters with much less computational efforts against the conventional FEMU.

A late-onset treatment-related changes (TRCs), which represent radiographic radiation necrosis (RN), frequently occur after stereotactic radiosurgery (SRS) for brain metastases and often need surgical treatment. This study aimed to validate the true pathology and investigate clinical implication of surgically resected TRCs on advanced magnetic resonance imaging (MRI). Retrospective analyses of 86 patients who underwent surgical resection after radiosurgery of brain metastases were performed. Fifty-four patients displayed TRCs on preoperative MRI, comprising pure RN in 19 patients (TRC-RN group) and mixed viable tumor cells in 35 patients (TRC-PD group). Thirty-two patients revealed the consistent diagnosis of progressive disease in both MRI and histopathology (PD–PD group). The TRC-PD group showed larger prescription isodose volume (9.4 cm3) than the TRC-RN (4.06 cm3, p = 0.014) group and a shorter time interval from SRS to preoperative MRI diagnosis (median 4.07 months) than the PD–PD group (median 8.77 months, p = 0.004). Progression-free survival was significantly different among the three groups (p

Although fatigue is a major symptom in patients with neuromyelitis optica spectrum disorder (NMOSD), the underlying mechanism remains unclear. We explored the relationship between subcortical structures and fatigue severity to identify neural substrates of fatigue in NMOSD. Clinical characteristics with brain magnetic resonance imaging were evaluated in forty patients with NMOSD. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-fatigue) questionnaire (a higher score indicates less fatigue). We assessed the correlation between subcortical structures and fatigue severity using surface-based shape analysis. Most of the enrolled patients showed fatigue (72.5%; mean FACIT-fatigue score, 34.8 ± 10.8). The FACIT-fatigue score was negatively correlated with Expanded Disability Status Scale and Beck Depression Inventory scores (r = − 0.382, p = 0.016; r = − 0.578, p

To evaluate the diagnostic performance, image quality, artifacts, and radiation doses of virtual non-contrast (VNC) images, relative to true non-contrast (TNC) images, in patients with surgically clipped aneurysms. Seventy-six patients who underwent unenhanced computed tomography (CT) and dual-energy (DE)-CT angiography after surgical clipping of 85 intracranial aneurysms were included in the study. Diagnostic performances of VNC and TNC images were compared with respect to sensitivity, specificity, and positive and negative predictive values. The results of quantitative and qualitative analyses were compared between VNC and TNC images. Radiation doses were also compared between VNC and TNC images. Diagnostic performance of VNC images was lower than that of TNC images; however, addition of contrast-enhanced images improved diagnostic performance. Image noise and mean attenuation of VNC images were significantly higher than those of TNC images in the centrum semiovale, cerebellum, and pons. The quality of VNC images was excellent or sufficient (85.5% for observer 1, 85.5% for observer 2), and complete acceptance of VNC images was achieved in 64.5% for observer 1 and in 71.0% for observer 2; however, the addition of contrast-enhanced images increased the level of acceptance (92.0% for observer 1, 90.9% for observer 2). Clip artifacts were significantly lower in VNC images than in TNC images. CT dose index, dose-length product, and effective dose were significantly lower without TNC images. VNC images showed lower diagnostic performance and image quality, and higher image noise than TNC images; however, VNC images could reduce clip artifacts and radiation doses.

Among mild cognitive impairment (MCI) patients, those with memory impairment (amnestic MCI, aMCI) are at a high risk of dementia. However, the precise cognitive domain, beside memory, that predicts dementia conversion is unclear. Therefore, we investigated the cognitive domain that predicts dementia conversion in a longitudinal aMCI cohort. We collected data of 482 aMCI patients who underwent neuropsychological tests and magnetic resonance imaging at baseline and were followed for at least 1 year. The patients were categorized according to number (1–4) and type of impaired cognitive domains (memory, language, visuospatial, and frontal-executive function). We evaluated dementia conversion risk in each group when compared to single-domain aMCI after controlling for age, education, diabetes and dyslipidemia. Baseline cortical thickness of each group was compared to that of 410 cognitively normal controls (NCs) after controlling for age, intracranial volume, diabetes and dyslipidemia. Compared to single-domain aMCI, aMCI patients with frontal-executive dysfunction at baseline had a higher risk of dementia conversion than aMCI patients with visuospatial or language dysfunction. Compared to NCs, aMCI patients with frontal-executive dysfunction had overall cortical thinning including frontal areas. Our findings suggest that aMCI patients with frontal-executive dysfunction have poor prognosis and,thus, should be considered for intervention therapy with a higher priority among aMCI patients.

The purpose of this study is to explore the role of logistics strategies (flexibility, collaboration, and differentiation) as antecedents of supply chain agility (SCA) and financial performance. Toward this end, we develop an integrative model based on the strategy–structure–performance paradigm, the resource-based view, and the relational view. Using structural equation modeling, we test the model with survey data gathered from 279 companies. The findings indicate that logistics strategies influence financial performance both directly and indirectly through SCA, providing empirical evidence for SCA’s central role in helping firms quickly sense and respond to changing environments.

Proximal middle cerebral artery (M1 segment) aneurysms are relatively deeply located in neighboring lenticulostriate arteries, which make them unsuitable for microsurgery. We aimed to investigate the clinical and radiological outcomes of endovascular coiling of M1 segment aneurysms. Between January 2003 and December 2014, we retrospectively reviewed the medical records of 52 patients (52 aneurysms) from four institutions who underwent endovascular coiling of M1 segment aneurysms. Patients who underwent clinical and radiologic follow-up for more than a year after the procedure were evaluated. The aneurysms were located in the early frontal branch, early temporal branch, and lenticulostriate artery in 28, 15, and nine patients, respectively. Endovascular coiling was achieved in 51 cases and failed in one case. Of these 51 cases, 46 (90.2%) and five (9.8%) were non-ruptured and ruptured aneurysms, respectively. Initial angiographic results revealed complete occlusion in 26 (51.0%), residual neck in 16 (31.4%), and residual sac in nine (17.6%) cases. One failed case had a symptomatic procedural complication of thromboembolism. However, there was no permanent morbidity or mortality. Two major recanalization cases (3.9%) were retreated by endovascular coiling. On multivariable logistic regression analysis, aneurysmal recurrence was significantly related to aneurysm height (OR, 1.887; 95% CI, 1.107 to 3.217; p = 0.020), width (OR, 1.836; CI, 1.127 to 2.992; p = 0.015), and neck (OR, 4.017; CI, 1.220 to 13.232, p = 0.022). Endovascular coiling of M1 segment aneurysms appeared to be a feasible treatment option with a relatively low-retreatment rate. Aneurysm size was statistically significantly associated with recurrence.

To determine the feasibility of using high dimensional computer-extracted features, known as radiomics features, in differentiating primary central nervous system lymphoma (PCNSL) from glioblastoma on multi-parametric MR imaging including diffusion-weighted imaging. Retrospective evaluation of data was approved by the local ethics committee and informed consent was waived. A total of 143 patients (two independent cohorts for discovery [n = 86; glioblastoma = 49, PCNSL = 37] and validation [n = 57; glioblastoma = 29, PCNSL = 28]) with newly diagnosed glioblastoma and PCNSL were subjected to radiomics analysis using the multi-parametric MRI (contrast-enhanced T1-weighted imaging, T2-weighted imaging, and diffusion-weighted imaging). Radiomics analyses were performed for two types of regions of interest (ROI) covering contrast-enhancing tumor and whole (enhancing or non-enhancing) tumor plus peritumoral edema. A total of 127 radiomics features were calculated. Feature selection was performed to identify the most discriminating features for every MR image in the discovery cohort. The identified features were used to calculate radiomics scores, which were later used in logistic regression to distinguish between PCNSL and glioblastoma. The classification model was further tested on the independent validation cohort. Fifteen features were selected as significant features in the discovery cohort. Using the identified features and calculated radiomics scores, the logistic regression-based classifier yielded an area under the curve (AUC) of 0.979, sensitivity of 0.938, and specificity of 0.944 in the discovery cohort to distinguish between glioblastoma and PCNSL. A similarly high rate of performance was observed in the validation cohort (AUC = 0.956). Radiomics features derived from multi-parametric MRI can be used to differentiate PCNSL from glioblastoma effectively.

Amyloid positron emission tomography ([18F] florbetaben (FBB) PET) can be used to determine concomitant Alzheimer's disease (AD) in idiopathic normal pressure hydrocephalus (iNPH) patients. FBB PET scans and the tap test were performed in 31 patients with clinically suspected iNPH, and amyloid positive (iNPH/FBB+) and negative (iNPH/FBB-) groups were compared with respect to clinical characteristics. We evaluated prognostic value of FBB PET scans by analyzing the response to the tap test using a linear mixed model. We also performed a multivariable regression analysis to investigate whether amyloid PET positivity can predict the positive tap test response independent of other AD biomarkers. The results showed that the iNPH/FBB+ group (7/31, 22.6%) had a higher percentage of APOE4 carriers, lower Aβ42, higher CSF t-tau, and p-tau/Aβ42 ratio than the iNPH/FBB- group (24/31, 77.4%), while the two groups did not differ in imaging characteristics. The iNPH/FBB- group had a higher percentage of tap responders and showed a greater improvement in gait scores after the tap test than the iNPH/FBB+ group (group-tap test effect interaction, p = 0.035). A multivariable logistic regression analysis showed that amyloid positivity on PET scans (OR 0.03, p = 0.029) and CSF p-tau (OR 0.87, p = 0.044) were independently associated with the positive tap test response. Among 21 tap responders in the iNPH/FBB- group, 14 patients received shunt surgery and 12/14 (85.7%) patients showed symptom improvement. Our findings suggest that amyloid PET scans can help determine which iNPH patients will benefit from shunt surgery by discriminating concomitant AD.

Melanocytes play an important role in maintaining epidermal homeostasis by producing melanin and protecting the skin from harmful environmental factors. However, excessive up- or down-regulation of melanin production often causes hyper- or hypo-pigmented disorders, respectively, which affect the patient's quality of life. Therefore, various strategies for modulating melanin levels have been developed by the pharmaceutical and cosmetic industries. We reported previously that voglibose, which is a well-known anti-hyperglycemic agent, could be used as an anti-melanogenic agent by inhibiting α-glucosidase activity and reducing tyrosinase protein levels. Of the other representative anti-hyperglycemic agents, acarbose showed less anti-melanogenic activity despite its potent anti-hyperglycemic efficacy. In this study, we report that acarbose exhibited considerable anti-melanogenic activity when melanocytes were co-treated with acarbose and a digestible sugar, such as maltose. Simultaneous treatment with maltose augmented the inhibitory effect of acarbose on α-glucosidase activity by enhancing its stability under physiological conditions, leading to the down-regulation of tyrosinase. These results suggest that the co-treatment of anti-hyperglycemic agents with hydrolysable sugars may be a useful tool for reducing glucosidase-associated melanogenesis as a potent sugar-based anti-melanogenic regimen.

Fibrosarcoma is a skin tumor that is frequently observed in humans, dogs, and cats. Despite unsightly appearance, studies on fibrosarcoma have not significantly progressed, due to a relatively mild tumor severity and a lower incidence than that of other epithelial tumors. Here, we focused on the role of a recently-found dermis zinc transporter, ZIP13, in fibrosarcoma progression. We generated two transformed cell lines from wild-type and ZIP13-KO mice-derived dermal fibroblasts by stably expressing the Simian Virus (SV) 40-T antigen. The ZIP13−/− cell line exhibited an impairment in autophagy, followed by hypersensitivity to nutrient deficiency. The autophagy impairment in the ZIP13−/− cell line was due to the low expression of LC3 gene and protein, and was restored by the DNA demethylating agent, 5-aza-2’-deoxycytidine (5-aza) treatment. Moreover, the DNA methyltransferase activity was significantly increased in the ZIP13−/− cell line, indicating the disturbance of epigenetic regulations. Autophagy inhibitors effectively inhibited the growth of fibrosarcoma with relatively minor damages to normal cells in xenograft assay. Our data show that proper control over autophagy and zinc homeostasis could allow for the development of a new therapeutic strategy to treat fibrosarcoma.

A Gram-negative, aerobic, non-motile, rod-shaped bacterial strain, designated MAB-07T, was isolated from the gut of a red snow crab. The novel strain grew optimally at 20 °C, pH 7.0–8.0, and in the presence of 3% (w/v) NaCl. A phylogenetic analysis based on the 16S rRNA gene sequence indicated that the strain MAB-07T belongs to the type strains of species of the genus Lacinutrix. Strain MAB-07T exhibited 16S rRNA gene sequence similarity values of 95.5–97.8% with the type strains of species of the genus Lacinutrix. The predominant cellular fatty acids of strain MAB-07T were iso-C15:1 G (27.5%) and iso-C15:0 (21.7%). The major respiratory quinine was identified as MK-6. The polar lipids consisted of phosphatidylethanolamine, four unidentified aminolipids, and two unidentified lipids. The genomic DNA G + C content was determined to be 33.3%, and its DNA–DNA relatedness values with the type strains of L. venerupis, L. mariniflava, L. jangbogonensis, L. algicola, and Olleya aquimaris were 28–32%. Based on the data from this polyphasic taxonomic study, strain MAB-07T is considered to represent a novel species of the genus Lacinutrix, for which the name L. chionocetis sp. nov. is proposed. The type strain is MAB-07T (=KCTC 42767T = JCM 30988T).

In the provision of on-demand personalized services in an IoT-based hyper-connected network, it is inevitable for the mobile device that centrally controls personal information to become the focal point. In this IoT environment, because mobile devices serve as a gateway for all personalized services, their protection plays a crucial role in the creation of a secure IoT environment. In the case of Android, the classic mobile platform, security is at risk from repackaging attacks because of structural weaknesses in the platform. To prevent such repackaging attacks, Android-based applications currently utilize various obfuscation techniques and insert tamper detection methods. However, it is possible to easily bypass even these measures. Thus, in this paper we propose an anti-reverse-engineering dynamic tamper detection scheme that applies image steganography to distribute and hide code in PNG image files. We design and implement this proposed scheme, and present the results of a security evaluation of an application with the scheme applied.

Background The protective effect of education has been well established in Alzheimer’s disease, whereas its role in patients with isolated cerebrovascular diseases remains unclear. We examined the correlation of education with cortical thickness and cerebral small vessel disease markers in patients with pure subcortical vascular mild cognitive impairment (svMCI) and patients with pure subcortical vascular dementia (SVaD). Methods We analyzed 45 patients with svMCI and 47 patients with SVaD with negative results on Pittsburgh compound B positron emission tomographic imaging who underwent structural brain magnetic resonance imaging. The main outcome was cortical thickness measured using surface-based morphometric analysis. We also assessed the volumes of white matter hyperintensities (WMH) and numbers of lacunes as other outcomes. To investigate the correlation of education with cortical thickness, WMH volume, and number of lacunes, multiple linear regression analyses were performed after controlling for covariates, including Mini Mental State Examination, in the svMCI and SVaD groups. Results In the SVaD group, higher education was correlated with more severe cortical thinning in the bilateral dorsolateral frontal, left medial frontal, and parahippocampal areas, whereas there was no correlation of education with cortical thickness in the svMCI group. There was no correlation between education and cerebral small vessel disease, including WMH and lacunes, in both patients with svMCI and patients with SVaD. Conclusions Our findings suggest that the compensatory effects of education on cortical thinning apply to patients with SVaD, which might be explained by the cognitive reserve hypothesis.

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The purpose of this study was to analyze outcomes in patients treated with gamma knife radiosurgery (GKS) for brain metastases from non-small cell lung cancer (NSCLC). We retrospectively reviewed the medical records of 817 patients who underwent GKS for brain metastases from NSCLC between January 2002 and December 2012. A total of 1363 GKS procedures were performed for 2970 lesions. The median overall survival time from the initial GKS was 13 months and the salvage treatment-free survival from the first GKS was 6.5 months. Younger age (≤65 years), female sex, better RPA class, higher DS-GPA score, adenocarcinoma, synchronous onset, and lower integrated value of the "numbers and cumulative volume of tumors" were associated with better outcomes. Among the 601 patients with an available follow up image, the pattern of the first progression after initial GKS was the development of new lesions in 356 patients (59.2 %), regrowth of treated lesions in 106 patients (17.6 %), and leptomeningeal seeding (LMS) in 51 patients (8.5 %). Among the deceased, the last MRI performed prior to death was evaluated in 409 patients and showed progression in 263 patients (64.3 %), despite multiple salvage treatments. LMS was identified in 63 patients (15.4 %); a rate much higher than the incidence at first progression. Intracranial tumor burden, defined as the integrated value of the "number of the lesions and cumulative tumor volume", is a new prognostic factor of greater significance than tumor volume or number alone when analyzed as separate factors. Although the cause of death was not progression of brain lesions in the majority of patients, the brain lesions tended to have been persistently progressive in most patients, despite repeated salvage treatment. LMS is an important pattern of treatment failure, in addition to local progression or development of new lesions, particularly in the terminal phase of the disease.

Bioorthogonal catalysis broadens the functional possibilities of intracellular chemistry. Effective delivery and regulation of synthetic catalytic systems in cells are challenging due to the complex intracellular environment and catalyst instability. Here, we report the fabrication of protein-sized bioorthogonal nanozymes through the encapsulation of hydrophobic transition metal catalysts into the monolayer of water-soluble gold nanoparticles. The activity of these catalysts can be reversibly controlled by binding a supramolecular cucurbit[7]uril 'gate-keeper' onto the monolayer surface, providing a biomimetic control mechanism that mimics the allosteric regulation of enzymes. The potential of this gated nanozyme for use in imaging and therapeutic applications was demonstrated through triggered cleavage of allylcarbamates for pro-fluorophore activation and propargyl groups for prodrug activation inside living cells.

Glioblastoma (GBM) is the most common and malignant brain tumor in adults. Despite therapeutic advances, almost all patients eventually experience tumor recurrence. Leptomeningeal spread (LMS) is not a rare condition of recurrence. However, the standard management protocol of LMS has not been established. The aim of this study is to report the risk of (LMS) and the prognosis between treatment modalities in GBM patients. A retrospective review was conducted of 321 patients who were diagnosed with GBM between January 2006 and December 2010. In 75 patients, LMS of tumor was detected by magnetic resonance image and/or cerebrospinal fluid cytology. Twelve patients underwent intrathecal methotrexate (IT-MTX) chemotherapy. Twenty-two patients underwent other salvage treatments. Forty-one patients underwent conservative management. We analyzed the possible clinical factors for LMS. Further, we examined overall survival and survival after diagnosis of LMS for several treatment modalities. In patients without LMS, median overall survival was 479 days, whereas that in patients with LMS it was 401 days. Younger age and larger initial tumor size were related to more frequent LMS incidence. Proximity between tumor margin and ventricle did not affect LMS. However, median duration from initial diagnosis to LMS was significantly different according to the distance to the ventricle. IT-MTX group’s overall survival was 583 days, which is statistically no longer than that of the other treatment group and the conservative management group. However, an additional survival benefit may exist compared to the conservative treatment. The median survival of the IT-MTX group was 181 days compared with 91 days for the conservative management group. Treatment of LMS is mainly palliative. IT-MTX is generally the first-line treatment modality of LMS. Prediction and prevention of LMS is crucial because its treatment has been limited. Further approaches to improve the therapeutic effect should be established.

Ethanol sclerotherapy has shown favorable short-term efficacy in managing head and neck arteriovenous malformation (AVM) which is well known for high recurrence rate after treatment. The purpose of this study was to report immediate treatment results and long-term follow-up results of ethanol sclerotherapy in patients with head and neck AVMs.We performed a retrospective review of 45 patients with head and neck AVMs treated between April 1997 and December 2013 by using ethanol sclerotherapy with or without adjunctive surgery. The degree of AVM eradication was analyzed, and complications per treatment session were recorded. Long-term treatment effectiveness was assessed with clinical and imaging follow-up.In total, 132 sclerotherapies were performed in the 45 patients, with a total angiographic eradication rate of 17.8% (n = 8). Partial resolution was achieved in 34 patients, and three patients showed no response. Mean follow-up period was 56.6 months (range, 13-144 months). The long-term recurrence rate was 11.1% (5/45), and all recurrences occurred more than 3 years after the treatment with interval disease-controlled period. The major complication rate was 3.8% (5/132), and 34 minor complications (25.8%) occurred.Ethanol sclerotherapy is effective for achieving long-term durable cure of head and neck AVMs. In patients with non-curable disease, it is also effective for symptom palliation and long-term disease control. However, given recurrence after interval disease-controlled period, long-term follow-up should be required to detect recurrence in patients with any residual lesion after treatment.

We investigated the frequency and clinical significance of diagonal earlobe crease (DELC) in cognitively impaired patients using imaging biomarkers, such as white matter hyperintensities (WMH) on MRI and amyloid-β (Aβ) PET. A total of 471 cognitively impaired patients and 243 cognitively normal (CN) individuals were included in this study. Compared with CN individuals, cognitively impaired patients had a greater frequency of DELC (OR 1.6, 95% CI 1.1–2.2, P = 0.007). This relationship was more prominent in patients with dementia (OR 1.8, 95% CI 1.2–2.7, P = 0.002) and subcortical vascular cognitive impairment (OR 2.4, 95% CI 1.6–3.6, P P

Tissue infarction is known as one of the characteristic features of invasive fungal sinusitis (IFS). The purpose of this study was to investigate the prevalence and characteristic MR imaging findings of cervicofacial tissue infarction (CFTI) associated with acute IFS. We retrospectively reviewed MR images in 23 patients with histologically or microbiologically proven acute IFS. CFTI was defined as an area of lack of enhancement in and around the sinonasal tract on contrast-enhanced T1-weighted images. We divided CFTI into two groups, i.e., intrasinonasal and extrasinonasal. Particular attention was paid to the location of extrasinonasal CFTI and the signal intensity of CFTI on T1- and T2-weighted images. The presence of bone destruction on CT scans was also recorded. CFTI was found in 17 (74 %) of 23 patients. All of these 17 patients had intrasinonasal CFTI, and 13 patients also had extrasinonasal CFTI. All 13 patients with extrasinonasal CFTI died of disease directly related to IFS. Various locations were involved in the 13 patients with extrasinonasal CFTI, including the orbit (n = 8), infratemporal fossa (n = 7), intracranial cavity (n = 3), and oral cavity and/or facial soft tissue (n = 4). Various signal intensities were noted at the area of CFTI on T1- and T2-weighted images. Bone destruction was found on CT scans in only 3 of 17 patients with CFTI. CFTI with preservation of the bony wall of the involved sinonasal tract may be a characteristic MR imaging finding of acute IFS. The mortality is very high once the lesion extends beyond the sinonasal tract.

A specific and sensitive liquid chromatography–tandem mass spectrometry (LC/MS/MS) in the negative electrospray ionization mode was developed and validated in order to analyze 3α-hydroxytibolone (3α-OH-tibolone), major metabolite of tibolone in human plasma sample using only 200 μL of plasma. 3α-OH-tibolone and 3α-OH-tibolone-d6 (internal standard, IS) in plasma were derivatized with p-toluenesulfonyl isocyanate after extraction using ethyl acetate. The dye residue and by-products was excluded using HLB Oasis SPE cartridge after derivertization. Separation of derivatized 3α-OH-tibolone and IS was performed on a C18 column within 6 min. The assay showed linearity in concentration ranges of 0.2–20 ng/mL. Intra-day precision and accuracy ranged from 0.77 to 5.0 % and from 98.0 to 100.56 %, respectively. Inter-assay precision and accuracy ranged from 1.49 to 5.00 % and from 99.75 to 100.94 %, respectively. A specific, reproducible and sensitive LC/MS/MS method for quantification of 3α-OH-tibolone in human plasma was successfully applied to evaluate the bioequivalence of tibolone in human volunteer following single oral administration of 5 mg tibolone.

Grain boundaries in graphene are formed by the joining of islands during the initial growth stage, and these boundaries govern transport properties and related device performance. Although information on the atomic rearrangement at graphene grain boundaries can be obtained using transmission electron microscopy and scanning tunnelling microscopy, large-scale information regarding the distribution of graphene grain boundaries is not easily accessible. Here we use optical microscopy to observe the grain boundaries of large-area graphene (grown on copper foil) directly, without transfer of the graphene. This imaging technique was realized by selectively oxidizing the underlying copper foil through graphene grain boundaries functionalized with O and OH radicals generated by ultraviolet irradiation under moisture-rich ambient conditions: selective diffusion of oxygen radicals through OH-functionalized defect sites was demonstrated by density functional calculations. The sheet resistance of large-area graphene decreased as the graphene grain sizes increased, but no strong correlation with the grain size of the copper was revealed, in contrast to a previous report. Furthermore, the influence of graphene grain boundaries on crack propagation (initialized by bending) and termination was clearly visualized using our technique. Our approach can be used as a simple protocol for evaluating the grain boundaries of other two-dimensional layered structures, such as boron nitride and exfoliated clays.

This study aimed to assess the efficacy of MR images with 3D T2-weighted turbo spin-echo (3D T2-TSE) sequences for early identification of postoperative cerebrospinal fluid (CSF) leaks. We analyzed the medical records and radiological reports for 72 consecutive patients who underwent an endoscopic endonasal approach for sellar and parasellar lesions between April 2009 and December 2010. Patients were 38 men and 34 women with a mean age of 46.4 years. All underwent MR scanning within 2 postoperative days, which included 3D T2-TSE sequences as well as a conventional T2-weighted (T2W) protocol. Sequence accuracy in predicting postoperative CSF leaks was assessed for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). A postoperative CSF leak was confirmed in 6 of 72 patients (8.3 %). On immediate postoperative MR images, 39 patients were suspicious for CSF leaks on conventional T2W sequences, while 18 patients on 3D T2-TSE. The 3D T2-TSE imaging had superior specificity and PPV (50 % vs. 81.8 %, 15.4 % vs. 33.3 %), while there was no difference in sensitivity and NPV compared with conventional T2W sequences. Compared to the conventional T2W protocol, MR imaging with the 3D T2-TSE protocol provides differential images around the sellar area with improved specificity and PPV for the detection of postoperative CSF leaks.

Salivary duct carcinoma (SDC) is an uncommon high grade adenocarcinoma of the salivary gland with a grave prognosis. The aim of this study was to investigate the clinical and CT and MR imaging features of SDC. We retrospectively evaluated the clinical and CT and MR imaging findings in 20 patients (14 men and six women; mean age, 59 years) with histologically proved SDC. We also tried to correlate clinicoradiological tumor staging with pathologic tumor staging in 17 patients who underwent surgery. The tumor originated in the parotid gland (n = 11; 55%), the submandibular gland (n = 7; 35%) and the buccal space along the distal Stensen's duct (n = 2; 10%). Locoregional recurrence occurred in 41% and distant metastasis in 47%. Fifty-eight percent died of the disease with a mean survival period of 32 months after diagnosis. On CT and MR images, SDC was mostly seen as an ill-defined (85%) and infiltrative (60%) mass with frequent calcification (50%) and necrosis (80%). Although various signal intensities were seen on MR images, six of nine tumors contained the areas of marked hypointensity on T2-weighted images. Clinicoradiological tumor staging correlated well with pathologic tumor staging in 82% of the patients. Ill-defined, infiltrative mass with calcification on CT scans and the areas of marked hypointensity on T2-weighted MR images may be useful radiologic features to suggest the diagnosis of SDC. CT and MR imaging are useful for staging of SDC.

Akt is serine/threonine protein kinase associated with various cellular processes and 3 different isoforms exist. This work describes the reproductive phenotype of Akt1-/- and Akt2-/- in male mice. The seminiferous tubule diameter in Akt1-/- testes was less than wild-type or Akt2-/- testes. The expression of phospho-phosphatase and tensin homologue deleted on chromosome 10 (p-PTEN) and phospho-glycogen synthase kinase 3β (GSK-3β) was elevated in Akt1-/- testes. Alterations in expression and localization to the plasma membrane of several facilitative glucose transporters (Slc2a8, 9a and 9b) were detected in these knockout compared to wild-type mice. Apoptotic sperm were more prevalent in both null mice compared to wild-type mice, whereas sperm concentration and motility were significantly lower in the null sperm. Finally, Akt2-/- sperm had a markedly decreased fertilization rate by in vitro fertilization (IVF) and resulting embryos displayed increased fragmentation and poor growth. These results suggest that altered SLC2A expression and increased PTEN and GSK3β activity may be responsible for the decreased spermatogenesis, sperm maturation, and fertilization in the Akt1-/- and Akt2-/- male mice.

Strong composition between FRP and concrete is an indispensable prerequisite to achieve the structural integrity of FRP-concrete composite deck. Accordingly, this study evaluates experimentally the behavioral characteristics of such shear connection systems realized by coarse sand coating and concrete wedge. The results show that coarse sand coating develops composite performance close to perfect composition in the shear direction but exhibits weakness against normal split. On the other hand, concrete wedge appears to be an efficient solution to resolve such problem. Therefore, a new shear connection system combining coarse sand coating and concrete wedge has been conceived and test revealed that the new shear connection system provides equivalent static performance together with significantly improved fatigue performance compared to the coarse sand coating composition. Following, the shear connection system combining both coarse sand coating and concrete wedge constitutes an efficient solution satisfying the strong composition requirement for the structural system.

The purpose of this study was to evaluate the signal intensity (SI) change of the labyrinth in patients with vestibular schwannoma on isotropic 3D fluid-attenuated inversion recovery (FLAIR) imaging at 3 T.Thirty-four patients with surgically confirmed or radiologically diagnosed vestibular schwannoma were included in this study. Retrospectively, we visually and quantitatively compared the SIs of the cochlea and vestibule on the affected side with those on the unaffected side. We also investigated whether there was correlation between the SI ratios (SIRs) of the labyrinth and the audiometric findings.On 3D FLAIR images, the SI of the cochlea and vestibule on the affected side was significantly increased in 97% (33/34) and 91% (31/34), respectively. While the SI of the cochlea was diffusely increased, that of the vestibule was only partially increased. Quantitative study also revealed statistically significantly higher SIRs of the cochlea (0.99 +/- 0.29) and vestibule (0.73 +/- 0.31) on the affected side, compared with the cochlea (0.47 +/- 0.20) and vestibule (0.19 +/- 0.10) on the unaffected side. There was no significant correlation of the SIRs of the labyrinth with the degree of hearing loss.In patients with vestibular schwannoma, isotropic 3D FLAIR imaging is a useful method for the evaluation of the SI changes of the labyrinth.

In Parkinson disease (PD), the dopaminergic (DAergic) neurons in the substantia nigra undergo degeneration. While the exact mechanism for the degeneration is still not completely understood, neuronal apoptosis and inflammation are thought to play roles. We have recently obtained evidence that matrix metalloproteinase (MMP)-3 plays a crucial role in the apoptotic signal in DAergic cells as well as activation of microglia. The present study tested whether doxycycline might modulate MMP-3 and provide neuroprotection of DAergic neurons. Doxycycline effectively suppressed the expression of MMP-3 induced in response to cellular stress in the DAergic CATH.a cells. This was accompanied by protection of CATH.a cells as well as primary cultured mesencephalic DAergic neurons via attenuation of apoptosis. The active form of MMP-3, released under the cell stress condition, was also decreased in the presence of doxycycline. In addition, doxycycline led to downregulation of MMP-3 in microglial BV-2 cells exposed to lipopolysaccharide (LPS). This was accompanied by suppression of production of nitric oxide and TNF-alpha, as well as gene expression of iNOS, TNF-alpha, IL-1beta, and COX-2. In vivo, doxycycline provided neuroprotection of the nigral DAergic neurons following MPTP treatment, as assessed by tyrosine hydroxylase immunocytochemistry and silver staining, and suppressed microglial activation and astrogliosis as assessed by Iba-1 and GFAP immunochemistry, respectively. Taken together, doxycycline showed neuroprotective effect on DAergic system both in vitro and in vivo and this appeared to derive from anti-apoptotic and anti-inflammatory mechanisms involving downregulation of MMP-3.

The objective of this study is to confirm the precise glucose transporter (GLUT) 8 localization and determine the expression of GLUT9a and GLUT9b by Western blot and confocal and immunoelectron microscopy in the mouse testis and sperm. GLUT8, GLUT9a, and GLUT9b proteins are expressed in the most intraseminiferous tubula cells and Leydig cells. GLUT8 localizes in the midpiece and principal piece as well as in the acrosomal region of the sperm. Immunoelectron microscopic analysis shows that GLUT8 is strongly detectable at the acrosome and neck region of the sperm. In the midpiece, GLUT8 localizes at the outer dense fibers (odf) as well as at the circumference of the spiral mitochondria. In the principal piece, GLUT8 localizes at the odf. GLUT9a strictly localizes in the midpiece, but GLUT9b localizes in the acrosome, midpiece, and principal piece of the sperm. These results suggest that glucose uptake via GLUT8, GLUT9a, and GLUT9b likely affects normal spermatogenesis, steroidogenesis, and sperm function in the mouse.

We introduce a high-performance molecular sensor using self-corrugated chemically modified graphene as a three dimensional (3D) structure that indicates anisotropic charge distribution. This is capable of room-temperature operation, and, in particular, exhibiting high sensitivity and reversible fast response with equilibrium region. The morphology consists of periodic, “cratered” arrays that can be formed by condensation and evaporation of graphene oxide (GO) solution on interdigitated electrodes. Subsequent hydrazine reduction, the corrugated edge area of the graphene layers have a high electric potential compared with flat graphene films. This local accumulation of electrons interacts with a large number of gas molecules. The sensitivity of 3D-graphene sensors significantly increases in the atmosphere of NO2 gas. The intriguing structures have several advantages for straightforward fabrication on patterned substrates, high-performance graphene sensors without post-annealing process.

A numerical model based on Berreman’s 4 × 4 matrix approach was developed and used for computational simulation of a cholesteric liquid crystal (CLC) polarizer. Explicit expressions of the 4 × 4 propagation matrices for several optical films, which constitute a CLC polarizer, were presented. Numerical simulations for optical properties of a CLC layer, a linear polarizer and a CLC polarizer were executed, and the simulated results were found to be in fairly good agreement with measured results.

We established an effective biolistic transformation procedure fortransferring foreign genes into garlic (Allium sativumL.),which we demonstrated by generating transgenic plants resistant tochlorsulfuron, a sulfonylurea herbicide. We subcultured callus tissue from theapical meristem of garlic cloves and repeatedly selected calli with brittle,non-mucilaginous surfaces for over six months, to increase transformationefficiency. We then constructed recombinant DNA that contained the acetolactatesynthase (ALS) gene from a chlorsulfuron-resistantArabidopsis mutant, the cauliflower mosaic virus 35Spromoter, the β-glucuronidase (GUS) reporter gene, and the hygromycinphosphotransferase (HPT) selectable marker gene. The garlic calli werebombarded twice with tungsten particles coated with the DNA constructs. Transformed calliwere efficiently selected by embedding them in solid agar medium containing 50mg l−1 hygromycin B. Selected propagules wereregenerated into 12 independent plants. We confirmed that the transgenes wereintegrated and expressed in the plants using PCR-Southern and Northern blotanalyses and by β-glucuronidase expression assay forGUS. The regenerated plants survived in the presence of 3mg l−1 chlorsulfuron, demonstrating that theirALS was insensitive to this herbicide. These results illustrate the successfultransformation of foreign genes into garlic plants. The set of proceduresdeveloped in this study is applicable to the generation of transgenic garlicplants with other agronomically beneficial traits.

An unconventional forming process using plastic pressure-building medium is presented to manufacture tee tube. A special experimental device was designed and built, and a three-dimensional rigid-plastic FEM code was developed to simulate the forming process. On the basis of the results of FEM simulation and experimental research, the plastic deformation of tee tube is divided into five different zones, which reveals the characteristics of metal deformation during the unconventional forming processes.

The toughening of epoxy modified with poly(butylene terephthalate)/poly(tetra-methylene glycol) (PBT–PTMG) copolymers of various chemical composition was investigated. The fracture toughness of the brittle epoxy was highly enhanced by the inclusion of PBT–PTMG copolymer without loss of other intrinsic mechanical properties, such as modulus and yield stress. These modified epoxies also exhibited synergism in toughening. The remarkable enhancement and the synergism in fracture toughness of PBT/PTMG-modified epoxies is possibly due to the enhancement of the degree of phase transformation toughening, which is a result of the enhancement of the degree of perfectness of PBT spherulites in the presence of PTMG segments. The changes in micro-morphology of PBT/PTMG phases induced by the different chemical composition of copolymer is the most important cause of the dependency of the fracture energy on the processing variables, such as the relative PBT/PTMG composition and total amount of modifiers. Other toughening mechanisms, such as crack bifurcation, ductile fracture of PBT/PTMG phases, main crack-path alteration, and crack bridging, also contributed to toughness enhancement of the modified epoxies. © 1998 Chapman & Hall

The structure and properties of ternary blends of epoxy with poly(ether sulphone) (PES) and carboxyl-terminated butadiene-acrylonitrile rubber (CTBN) have been investigated. In these blends, the phase separation occurs in two stages: a macrophase separation during mixing and a microphase separation during curing. At low PES compositions, the PES-rich spherical domains are dispersed. With increasing PES composition, a co-continuous structure develops and, eventually, the phases are inverted. Regardless of structure change, the modulus and yield stress changes with composition just follow the simple rule of mixtures. However, the fracture toughness of these blends exhibits a synergistic effect. Among the various compositions, 5∶5 weight ratio of CTBN to PES exhibited the maximum toughness, which was 140% larger than that calculated from the rule of mixtures. The synergism is believed to be due to the bridging by the PES-rich phase followed by a lowering of the yield stress. The lowering of the yield stress can enlarge the process zone size and the amount of plastic dilatation of the matrix.

The microstructural variation and the interdiffusion of Pt (80 nm)/Ti (70 nm)/SiO2/Si during annealing in O2 were investigated using Auger electron spectroscopy, x-ray diffraction, transmission electron microscopy, and scanning electron microscopy. While the as-deposited and 400 °C annealed samples showed well-defined layer structures without any significant interfacial reaction, the degree of oxidation remarkably increased with increasing temperature above 500 °C. The PtTi alloy phase with Pmma structure (AuCd type) was observed from the 500 °C annealed sample. Drastic interdiffusion occurring above 600 °C changed the Pt/Ti bilayer into a very entangled structure. Some TiO2 phases were exposed to the ambient between Pt hillocks. In addition, a small amount of Pt-silicide was found near the TiOx/SiO2 interface.

Background Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC. Methods Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy. Results Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008). Conclusion Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC.

Cu-Cu2O eutectic bonding of copper to alumina has been studied at 1075°C in nitrogen gas. In order to elucidate the reaction at the Cu/Al2O3 interface, the bonding time was prolonged up to 24 h at 1075°C in nitrogen gas. CuAlO2 was found at the Cu/Al2O3 interface, and it seems that CuAlO2 was formed even with a short bonding time. CuAlO2 enhanced the bonding strength. There seem to be two kinds of bonding mechanism working at the Cu/Al2O3 interface.

Due to a rapid shrinkage in memory devices, backned of the line process experiences great difficulties, especially Al metallization. Furthermore, there is a continuous demands in low line resistance in order to promote device performances. In this article, Al damascene process is proposed as compared to Al patterning process, which suffers from inherent pattering issue at a fine pitch under 70nm. The most difficulties in the development of Al damascene process were to form a stable and void free Al in fine trench and to obtain scratch and corrosions free Al surface. In this study, 50nm beyond fill was successfully achieved by “bottom up growth” of CVD Al. For the process, CVD Al by using Methylpyrroridine Alane (MPA) precursor was deposited on a stacked film of CVD TiN and PVD TiN as a wetting layer, which was followed by PVD Al and reflow, then the Al surface was polished with colloidal silica based slurry.In addition, electrical property of Al scheme and W scheme was compared with damascene pattern, along with which we demonstrated that around 36% decrease in parasitic capacitance is achievable by decrease of metal line height from 3500A to 1000A on simulation test implying that device performance could be enhanced.

Thin film electrodes of the perovskite oxide (Ba,Sr)RuO3 (BSR) were deposited on 4 inch ptype Si wafers by metal organic chemical vapor deposition (MOCVD) for the practical (Ba,Sr)TiO3 (BST) capacitor application using a new single cocktail source. The source materials used for the MOCVD BSR process were Ba(METHD)2, Sr(METHD)2 and Ru(METHD)3 and these were dissolved in n-butyl acetate. The source-feeding rate was precisely controlled by liquid mass flow controllers (LMFC). As-deposited BSR films possessed a (110)-oriented structure, with good uniformity and adherence on bare Si wafer. The phase formation was strongly affected by the oxygen flow rate and the input source rate. As the oxygen flow rate increased, the Ru/(Ba+Sr) composition ratio in the film decreased, while the Ba/(Ba+Sr) ratio was almost independent of the oxygen flow rate. The dielectric constants of BST capacitors fabricated using these electrodes was greater than 500.

Perovskite-phase lead zirconate titanate (PZT) thin films were fabricated at 4751C by the electron cyclotron resonance (ECR) plasma enhanced DC magnetron multi-target reactive sputtering method on Pt/Ti/SiO2/Si and Pt/SiO2/Si substrates. Stoichiometric perovskite PZT films were readily obtained on Pt/Ti/SiO2/Si substrates because Ti atoms which were out-diffused to the Pt surface facilitated Pb incorporation by forming lead titanate at the early stage of deposition process. Activation of oxygen by ECR plasma facilitated the oxidation reaction and Pb incorporation into the film. Thus perovskite-phase PZT can be obtained on the Pt/SiO2/Si substrate.

The crystallization process and microstructural evolution of PZT (52/48) thin films deposited on Pt thin film electrode on Si (100) by reactive multitarget cosputtering technique have been studied as a function of post-annealing temperature and holding time. As annealing temperature increases, the Amorphous PZT films as-deposited at low substrate temperature of 200 °C crystallize into pyrochlore at 450 °C and ferroelectric perovskite phase with pseudo-cubic structure at 550 °C in sequence. X-ray diffraction data show crystallization into perovskite phase to be complete in 30 Minutes at 550 °C. Furthermore, the change of PZT/Pt/Ti/SiO2/Si interfacial TEM Morphology during heat-treatment has been closely scrutinized.