Because Cu is an austenite γ stabilizer, it is thought that Cu only dissolves in the FCC γ phase but not in the BCC δ when Cu-containing PHSS are treated in a dual δ-γ solid solution at high ...temperature. However, the nano precipitation of Cu in the allotriomorphic δ found upon quenching from 1295°C. To study this unexpected phenomenon, thermodynamic calculations were performed. The predicted solubilities of Cu in the γ and δ at 1295°C were 3.52 and 1.99 wt%. Consequently, quenching the solid solution from 1295 to 25°C results in the ultra-supersaturation of Cu in the δ. The vacancy concentration in the δ solution was estimated to change from 1024 vac./m3 at 1295°C to105 vac./m3 at 25°C; quenching yields excess vacancies. Thus, Cu-rich nanoparticles precipitate in the δ matrix through the interdiffusion of the ultra-supersaturated Cu and excess vacancies.
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Motivated by the needs to enhance the performance of garbage collection in low-cost flash storage devices, we propose a victim block selection design to efficiently identify the blocks for erases and ...reclaim the space of invalid data without extensively scanning flash memory for the data status stored in the storage, so as to improve the garbage collection performance on reclaiming the space of invalid data. Moreover, this design could easily identify and reclaim the space released by file systems. Experiments based on benchmark traces show significant performance improvement of garbage collection with limited system overheads.
In prosthodontics, the ability of glass-ceramics to express the optical properties of natural teeth is an important goal of esthetic restorations. Dental restorations do not merely need to be similar ...in color to natural teeth; proper optical properties, such as opalescence, transparency, etc., must be combined in order to achieve excellent esthetic effects. The optical properties of ceramic materials are mainly distinguished by different hues (e.g., A, B, C, and D) combined with translucency (e.g., high translucency (HT), medium translucency (MT), low translucency (LT), and medium opacity (MO)). However, there are many varieties of tooth color. Therefore, it is expected that glass-ceramics can change their nanocrystal size and porosity through different heat-treatment temperatures and times and, thereby, present different transparency effects. This study mainly analyzed the influence of changes in sintering temperature on the optical properties of glass-ceramics. The optical properties of glass-ceramics in the oral cavity were evaluated with human trials. We hypothesized that (1) the transparency of glass-ceramics can be changed by controlling the sintering temperature and (2) glass-ceramics modified by the sintering temperature can be suitable for clinical applications. Results showed that the transparency decreased, the nanoparticle size increased, the crystallinity increased, and the surface hardness decreased as the sintering temperature increased. High-brightness glass-ceramics have more-sensitive optical properties. Results of clinical trials showed that glass-ceramics whose transparency was changed by controlling the sintering temperature can be candidates for clinical applications. Based on the above results, the hypotheses of this study were supported. In the future, we will continue to explore the esthetic field of dental restorations.
Sinulariolide, an active compound isolated from the cultured soft coral Sinularia flexibilis, has potent anti-microbial and anti-tumorigenesis effects towards melanoma and bladder cancer cells. In ...this study, we investigated the effects of sinulariolide on hepatocellular carcinoma (HCC) cell growth and protein expression. Sinulariolide suppressed the proliferation and colony formation of HCC HA22T cells in a dose-dependent manner and induced both early and late apoptosis according to flow cytometry, Annexin V/PI stain and TUNEL/DAPI stain analyses. A mechanistic analysis demonstrated that sinulariolide-induced apoptosis was activated through a mitochondria-related pathway, showing up-regulation of Bax, Bad and AIF, and down- regulation of Bcl-2, Bcl-xL, MCl-1 and p-Bad. Sinulariolide treatment led to loss of the mitochondrial membrane potential, release of mitochondrial cytochrome c to the cytosol, and activation of both caspase-9 and caspase-3. Sinulariolide-induced apoptosis was significantly blocked by the caspase inhibitors Z-VAD-FMK and Z-DEVD-FMK. The increased expression of cleaved PARP also suggested that caspase-independent apoptotic pathway was involved. In the western blotting; the elevation of ER chaperones GRP78; GRP94; and CALR; as well as up-regulations of PERK/eIF2α/ATF4/CHOP; and diminished cell death with pre-treatment of eIF2α phosphatase inhibitor; salubrinal; implicated the involvement of ER stress-mediated PERK/eIF2α/ATF4/CHOP apoptotic pathway following sinulariolide treatment in hepatoma cells. The current study suggested sinulariolide-induced hepatoma cell cytotoxicity involved multiple apoptotic signal pathways. This may implicate that sinulariolide is a potential compound for the treatment of hepatocellular carcinoma.
Background
In the treatment of oral cavity squamous cell carcinoma (OCSCC), surgical quality measures which are expected to affect outcomes, including the achievement of a clear margin, are ...surgeon-dependent but might not be invariably associated with hospital volume. Our objective was to explore surgical margin variations and survival differences of OCSCC between two highest-volume hospitals in Taiwan.
Materials and methods
A total of 2009 and 1019 patients with OCSCC who were treated at the two highest-volume Taiwanese hospitals (termed Hospital 1 and Hospital 2, respectively) were included. We examined how a pathological margin <5 mm impacted patient outcomes before and after propensity score (PS) matching.
Results
The prevalence of margins <5 mm was markedly lower in Hospital 1 than in Hospital 2 (34.5%/65.2%,
p
<0.0001). Compared with Hospital 2, tumor severity was higher in Hospital 1. On univariable analysis, being treated in Hospital 2 (versus Hospital 1; hazard ratio HR for 5-year disease-specific survival DSS = 1.34,
p
=0.0002; HR for 5-year overall survival OS = 1.17,
p
=0.0271) and margins <5 mm (versus ≥5 mm; HR for 5-year DSS = 1.63,
p
<0.0001; HR for 5-year OS = 1.48,
p
<0.0001) were identified as adverse factors. The associations of treatment in Hospital 2 and margins <5 mm with less favorable outcomes remained significant after adjustment for potential confounders in multivariable analyses, as well as in the PS-matched cohort. The 5-year survival differences between patients operated in Hospital 1 and Hospital 2 were even more pronounced in the PS-matched cohort (before PS matching: DSS, 79%/74%,
p
=0.0002; OS, 71%/68%,
p
=0.0269; after PS matching: DSS, 84%/72%,
p
<0.0001; OS, 75%/66%,
p
<0.0001). In the entire cohort, the rate of adjuvant therapy was found to be lower in patients with margins ≥5 mm than in those with margins <5 mm (42.7%
/
57.0%,
p
<0.0001).
Conclusions
Within the two highest-volume hospitals in Taiwan, patients with OCSCC with a clear margin status (≥5 mm) achieved more favorable outcomes. These results have clinical implications and show how initiatives aimed at improving the margin quality can translate in better outcomes. A clear margin status can reduce the need for adjuvant therapy, ultimately improving quality of life.
e14671 Background: OBI-833/OBI-821 (OBI-833) is a novel active immune therapy (cancer vaccine) targeting a tumor-associated carbohydrate antigen, Globo H. Previous reports have shown that OBI-833 can ...elicit a beneficial immune response in Non-Small Cell Lung Cancer (NSCLC) patients and rendered durable stable disease with some TKI-treated patients. In this study, we further evaluated the effect of OBI-833-induced immune responses on the in-study progression-free survivals (isPFS) during the treatment. Methods: Sera were collected for the evaluations of maximum concentration (Cmax) and exposure (area under the curve: AUC) of anti-Globo H IgM (GH IgM) and IgG (GH IgG), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and ex-vivo GH IgM induction with PBMC from each subject at baseline. The correlations of OBI-833-induced immune responses with isPFS and best overall response (BOR) were also evaluated. Pearson correlation coefficient analysis was used for all correlation evaluations. Results: Among the 14 OBI-833-treated subjects, 93% and 64% of subjects had significant increase in GH IgM and GH IgG, respectively. Median Cmax GH IgM and Cmax GH IgG were 13.8 µg/mL and 12.4 µg/mL, respectively. While the increase in CDC activities was not significantly correlated with the increase of GH IgM, a weak association between GH IgG and ADCC was observed (r=0.3380, p<0.0001). In addition, a strong association (r=0.84) was observed between Ex-vivo IFN-γ secreting and their Cmax IgM concentration in the OBI-833 Ex-vivo stimulation study. In contrast, weak association (r=0.26) was observed between Ex-vivo GH IgM induction and their Cmax of IgM. Correlations of the immune responses on isPFS were further analyzed. Significant positive correlations were observed for the Cmax and AUC of GH IgM with isPFS (Cmax: r=0.6345, p=0.0148; AUC: r=0.8212, p=0.0003) and the Cmax and AUC of GH IgG with isPFS (Cmax: r=0.7192, p=0.0037; AUC: r=0.6306, p=0.0062). Furthermore, distinct features of GH IgG responses from 2 subjects were identified based on the ADCC-GH IgG scatter plot. Samples from subject 034-006 showed high ADCC activity with relatively low GH IgG concentration, whereas the BOR was at -27%, which has significant negative correlation of tumor response (TR) with GH IgG (r=-0.7381, p=0.0148) and ADCC (r=-0.8565, p=0.0016). In contrast, samples from subject 034-004 showed average ADCC activity and relatively high GH IgG concentration with BOR at -12%, showing a negative correlation of TR with GH IgG (r=-0.8352, p=0.0001) and ADCC (r=-0.5690, p=0.0269). Conclusions: OBI-833 can elicit beneficial immune responses in NSCLC patients. Both GH IgM and GH IgG may contribute to the isPFS and TR of the subjects. Further development of OBI-833 in EGFR-mutated NSCLC patients phase II trial is ongoing.
In quantitative risk analyses for natural hazards, vulnerability can be expressed as the ratio of reconstruction, replacement or reproduction expenses due to a damage caused by a certain process ...intensity and the original value of the element at risk exposed. To discuss the building vulnerability under debris flow events, the ratio is mostly related to debris flow inundation height, building materials and building values. Different types of buildings would resist to the impact of debris flows differently, resulting in different damage levels even under the same inundation height. After debris flow events, the damages to a building include the content loss and the structure loss, which is also variable due to the individual building conditions. This study proposes a flowchart to establish building vulnerability curves through estimating the damages to buildings after debris flow hazards. The losses of content and structure are firstly calculated separately to obtain the loss ratios with respect to original buildings. Secondly, by combining the content and structure loss ratio, the building vulnerability function is derived. In this paper, the original building content value was obtained from governmental statistic records and was based on the market price, and the structure value was received from a regional architecture office. The losses resulting from debris flow impacts were synthetically derived following field surveys. To combine the content and structure losses, a unit building with a floor area of 60 m
2
was assumed. The result shows that due to a higher percentage of content value compared with the total building value, the loss ratio resulting from debris flows in Taiwan is higher compared with European studies, in particular with respect to high-frequency but low-magnitude events. The concept of obtaining building vulnerability is particularly suitable for regions where well-documented building loss records are unavailable.
Huntington’s disease (HD) belongs to protein misfolding disorders associated with polyglutamine (polyQ)-rich mutant huntingtin (mHtt) protein inclusions. Currently, it is indicated that the ...aggregation of polyQ-rich mHtt participates in neuronal toxicity and dysfunction. Here, we designed and synthesized a polyglutamine-specific gold nanoparticle (AuNP) complex, which specifically targeted mHtt and alleviated its toxicity. The polyglutamine-specific AuNPs were prepared by decorating the surface of AuNPs with an amphiphilic peptide (JLD1) consisting of both polyglutamine-binding sequences and negatively charged sequences. By applying the polyQ aggregation model system, we demonstrated that AuNPs–JLD1 dissociated the fibrillary aggregates from the polyQ peptide and reduced its β-sheet content in a concentration-dependent manner. By further integrating polyethyleneimine (PEI) onto AuNPs–JLD1, we generated a complex (AuNPs–JLD1–PEI). We showed that this complex could penetrate cells, bind to cytosolic mHtt proteins, dissociate mHtt inclusions, reduce mHtt oligomers, and ameliorate mHtt-induced toxicity. AuNPs–JLD1–PEI was also able to be transported to the brain and improved the functional deterioration in the HD Drosophila larva model. Our results revealed the feasibility of combining AuNPs, JLD1s, and cell-penetrating polymers against mHtt protein aggregation and oligomerization, which hinted on the early therapeutic strategies against HD.
The structural characterization correlated to the processing control of hierarchical structure of planar heterojunction perovskite layer is still incomplete due to the limitations of conventional ...microscopy and X-ray diffraction. This present study performed the simultaneously grazing-incidence small-angle scattering and wide-angle scattering (GISAXS/GIWAXS) techniques to quantitatively probe the hierarchical structure of the planar heterojunction perovskite solar cells. The result is complementary to the currently microscopic study. Correlation between the crystallization behavior, crystal orientation, nano- and meso-scale internal structure and surface morphology of perovskite film as functions of various processing control parameters is reported for the first time. The structural transition from the fractal pore network to the surface fractal can be tuned by the chloride percentage. The GISAXS/GIWAXS measurement provides the comprehensive understanding of concurrent evolution of the film morphology and crystallization correlated to the high performance. The result can provide the insight into formation mechanism and rational synthesis design.
(1) Background: Betel nut chewing injures bodily health. Although, the relationship between betel nut chewing and kidney stone disease (KSD) is unknown. (2) Methods: We analyzed 43,636 men from ...Taiwan Biobank. We divided them into two groups on the status of betel nut chewing, the never-chewer and ever-chewer groups. Self-reported diagnosed KSD was defined as the subject's medical history of KSD in the questionnaire. Logistic regression was used to analyze the association of betel nut chewing and the risk of KSD. (3) Results: The mean age of subjects in the present study was 50 years, and 16% were ever-chewers. KSD was observed in 3759 (10.3%) and 894 (12.6%) participants in the group of never-chewer and ever-chewer groups, respectively. Higher risk of KSD was found in participants with betel nut chewing compared with to without betel nut chewing (odds ratio (OR), 1.094; 95% confidence interval (95% CI), 1.001 to 1.196). Furthermore, the daily amounts of betel nut chewing >30 quids was associated with a more than 1.5-fold increase (OR, 1.571; 95% CI, 1.186 to 2.079) in the odds of KSD; (4) Conclusions: Our study suggests that betel nut chewing is associated with the risk of KSD and warrants further attention to this problem.
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