Patient-derived xenograft (PDX) tumor model has become a new approach in identifying druggable tumor mutations, screening and evaluating personalized cancer drugs based on the mutated targets.
We ...established five nasopharyngeal carcinoma (NPC) PDXs in mouse model. Subsequently, whole-exome sequencing (WES) and genomic mutation analyses were performed to search for genetic alterations for new drug targets. Potential drugs were applied in two NPC PDX mice model to assess their anti-cancer activities. RNA sequencing and transcriptomic analysis were performed in one NPC PDX mice to correlate with the efficacy of the anti-cancer drugs.
A relative high incident rate of copy number variations (CNVs) of cell cycle-associated genes. Among the five NPC-PDXs, three had cyclin D1 (CCND1) amplification while four had cyclin-dependent kinase inhibitor CDKN2A deletion. Furthermore, CCND1 overexpression was observed in > 90% FFPE clinical metastatic NPC tumors (87/91) and was associated with poor outcomes. CNV analysis disclosed that plasma CCND1/CDKN2A ratio is correlated with EBV DNA load in NPC patients' plasma and could serve as a screening test to select potential CDK4/6 inhibitor treatment candidates. Based on our NPC PDX model and RNA sequencing, Palbociclib, a cyclin-dependent kinase inhibitor, proved to have anti-tumor effects by inducing G1 arrest. One NPC patient with liver metastatic was treated with Palbociclib, had stable disease response and a drop in Epstein Barr virus (EBV) EBV titer.
Our integrated information of sequencing-based genomic studies and tumor transcriptomes with drug treatment in NPC-PDX models provided guidelines for personalized precision treatments and revealed a cyclin-dependent kinase inhibitor Palbociclib as a novel candidate drug for NPC.
Blended learning, thoughtfully combining the best elements of online and face-to-face education, is likely to emerge as the predominant teaching model of the future. In this paper, we present a ...blended learning environment combining mobile learning, web-based learning, and classroom teaching to provide realistic, practical opportunities for learners and teachers to engage in problem solving activities. The purpose of this study was to explore problem solving patterns and their impact on learning achievement in a blended learning environment. Through quasi-experimental instruction, we collected all of the data of the learning processes from 34 students in a blended learning environment using classroom instruction, mobile and web scenarios. By combining cluster analysis and content analysis, we were able to identify three groups with distinct characteristics: the hybrid-oriented group, the technology-oriented group, and the efficiency-oriented group. Learners in the hybrid-oriented group used the classroom, mobile and web scenario almost equally. They displayed a regular manner in following the instructor’s teaching procedure, and tended to passively accept whatever the teacher said. Students in the technology-oriented group spent most of their time using mobile and web technologies but they revealed superficial problem solving abilities such as a lack of understanding and planning. The efficiency-oriented group was characterized by the efficient monitoring of learning processes. It was more task-oriented and performed better than the other two groups.
► Students in the efficiency-oriented group performed better than those in the hybrid-oriented group and the technology-oriented group on problem-solving performance.►Learners categorized in the hybrid-oriented group to followed the teacher's step-by-step instructions in a regular manner.►Students in this group made equal use of mobile, web-based and classroom environment, but failed to consider the reason for doing so, during the problem solving process. ►Learners in the technology-oriented group spent more time using technological tools than the other two groups, but this did not guarantee improved learning achievement.
With the dramatic increase of photovoltaic (PV) module installation in solar energy-based industries, the methods for recovering waste solar generators should be emphasized as the backup of the PV ...market for environmental protection. Crystalline-silicon accounts for most of the worldwide PV market and it contains valuable materials such as high purity of silicon (Si), silver (Ag), copper (Cu), tin (Sn), and lead (Pb). This study can provide an efficient recycling process for valuable materials resourced from waste crystalline-silicon PV module, including Si in the PV cell, and Ag, Cu, Pb, Sn, in PV ribbon. As tempered glass and Ethylene Vinyl Acetate (EVA) resin were removed, the module was separated into two materials, PV ribbon and PV cell. For PV cell purification, Si with purity at 99.84% was recovered by removing impurities such as aluminum (Al) and Ag by two-step leaching and dissolving the impurities. For PV ribbon recovering, purified metal or metal oxide was obtained through the processes of leaching/polishing, extraction, and chemical precipitation. In the polishing process, 99.5% of copper wire was collected. The purities of final products are 99.7% for CuO, 99.47% for PbO, 99.68% for SnO2, and 98.85% for Ag respectively.
On 31 August 2010, more than 100 transient luminous events were observed to occur over Typhoon Lionrock when it passed at ∼210 km to the southwest of the NCKU site in Taiwan. Among them, 14 negative ...gigantic jets (GJs) with clear recognizable morphologies and radio frequency signals are analyzed. These GJs are all found to have negative discharge polarity and thus are type I GJs. Morphologically, they are grouped into three forms: tree‐like, carrot‐like, and a new intermediate type called tree‐carrot‐like GJs. The ULF and ELF/VLF band signals of these events contain clear signatures associated with GJ development stages, including the initiating lightning, the leading jet, the fully developed jet, and the trailing jet. Though the radio waveform for each group of GJs always contains a fast descending pulse linked with the surge current upon the GJ‐ionosphere contact, the detailed waveforms actually vary substantially. Cross analysis of the optical and radio frequency signals for these GJs indicates that a large surge current moment (CM) (>60 kA‐km) appears to be essentially associated with the tree‐like GJs. In contrast, the carrot‐like and the tree‐carrot‐like GJs are both related to a surge CM less than 36 kA‐km, and a continuing CM less than 27 kA‐km further separates the carrot‐like GJs from the tree‐carrot‐like GJs. Furthermore, on the peak CM versus charge moment change diagram for the initiating lightning, different groups of GJs seem to exhibit different trends. This feature suggests that the eventual forms of negative GJs may have been determined at the initiating lightning stage.
Key Points
From the morphology, the negative gigantic jets can be grouped into three forms
The radio signals of the GJs contain clear signatures in various GJ development
From the derived physical parameters, the formations of these GJs are explained
Rat Bait, Not Healthy Rice Lee, Kuan-I; Lin, Jing-Hua; Chu, Yen-Jung ...
Toxics,
01/2023, Letnik:
11, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Bromadiolone, a potent, long-acting anticoagulant rodenticide is frequently tinted to a red or pink color and mixed with cereals as rat bait. Six peoples working in a small factory suffered from a ...severe bleeding tendency several weeks after consuming a rice meal that was tainted with bromadiolone mistaken to be healthy food. High serum levels of bromadiolone and excessive bleeding were found in these individuals, and they needed vitamin K1 therapy for weeks. These cases indicated that long-acting anticoagulant rodenticide might induce cumulative toxicity in repeated, low-dose exposure, and the blood levels of bromadiolone might be an indicator for antidote therapy if available.
Background
Breast cancer is a heterogeneous and complex etiological disease. Understanding perturbations of circulating metabolites could improve prognosis.
Methods
We recruited breast cancer ...patients from Kaohsiung Medical University (KMU) to perform untargeted (case–control design) and targeted (patient cohort) metabolomics analyses in the discovery and validation phases to evaluate interaction effects between clinical factors and plasma metabolites using multivariable Cox proportional hazards model.
Results
In the discovery phase, partial least squares-discriminant analysis (PLS-DA) showed that plasma metabolites were significantly different between recurrent and non-recurrent breast cancer patients. Metabolite set enrichment analysis (MSEA) and metabolomic pathway analysis (MetPA) showed that valine, leucine, and isoleucine degradation was the significant pathway, and volcano plot showed significant ten upregulated and two downregulated metabolites between recurrent and non-recurrent cases. Combined with receiver operating characteristic (ROC) curve and biological significance, creatine, valine, methionine, and mannose were selected for the validation phase. In this patient cohort with 41 new-recurrent vs. 248 non-recurrent breast cancer cases, followed for 720.49 person-years, compared with low level of valine, high valine level was significantly negatively associated with recurrent breast cancer (aHR: 0.36, 95% CI: 0.18–0.72,
P
= 0.004), especially in ER-negative and PR-negative status. There were interaction effects between valine and ER (
P
interaction
= 0.006) as well as PR (
P
interaction
= 0.002) on recurrent breast cancer. After Bonferroni correction, stratification effects between valine and hormone receptors were still significant.
Conclusion
Our study revealed that plasma metabolites were significantly different between recurrent and non-recurrent patients, proposing therapeutic insights for breast cancer prognosis.
For the first time, the photovoltaic modules composed of small molecule were successfully fabricated by using roll-to-roll compatible printing techniques. In this study, blend films of small ...molecules, BTR and PC71BM were slot-die coated using a halogen-free solvent system. As a result, high efficiencies of 7.46% and 6.56% were achieved from time-consuming solvent vapor annealing (SVA) treatment and roll-to-roll compatible solvent additive approaches, respectively. After successful verification of our roll-to-roll compatible method on small-area devices, we further fabricated large-area photovoltaic modules with a total active area of 10 cm2, achieving a power conversion efficiency (PCE) of 4.83%. This demonstration of large-area photovoltaic modules through roll-to-roll compatible printing methods, even based on a halogen-free solvent, suggests the great potential for the industrial-scale production of organic solar cells (OSCs).
Background/Aim: Triple negative breast cancer (TNBC) is one of the most challenging breast cancer types. Interleukin-8 (IL-8) is a pro-tumorigenic cytokine, promoting tumor proliferation and ...migration. This study aimed to examine the contribution of IL-8 rs4073 genotypes to breast cancer risk and provide a summary of related literature. Materials and Methods: IL-8 genotypic profiles were determined among 1,232 breast cancer cases and 1,232 controls via polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The IL-8 rs4073 AT and AA genotypes had significantly lower prevalence in the case group compared to control group. Allelic frequency analysis showed that individuals carrying the A allele have relatively decreased risk for breast cancer. The stratification analysis showed that IL-8 rs4073 genotypes were protective markers for those with younger (≤55) age. Conclusion: IL-8 rs4073 A allele is a novel predictor for breast cancer, especially TNBC.
This paper examines whether outstanding employee stock options (ESOs), which represent the firm's contractual obligation to deliver shares upon ESO exercise, affect firms' credit ratings. I ...hypothesize that outstanding ESOs play two information roles-(1) suggesting equity infusion, and (2) predicting share repurchases-that help credit-rating agencies evaluate the issuing company's debt service ability. Consistent with these hypothesized roles, results indicate that the present values of expected cash proceeds and tax benefits from ESO exercise have favorable effects on credit ratings. In contrast, the present value of the expected cost of ESO-related share repurchases has an unfavorable effect on credit ratings and this unfavorable effect is more pronounced for firms with a greater tendency to repurchase shares. The after-tax fair value of outstanding ESOs, which summarizes the effects of the above three ESO-related cash flows, is negatively associated with credit ratings. Taken together, these findings are consistent with credit-rating agencies incorporating the information conveyed by outstanding ESOs regarding potential equity infusion and ESO-related repurchases in their credit risk assessments and assigning lower credit ratings to firms with greater values of outstanding ESOs.
We perform a comprehensive study to achieve better polyelectrolytes (PEs) as electron-transport layers (ETLs) in polymer solar cells (PSCs). Three well-known PEs – PFN, PEIE, and WPF – are chosen as ...model systems and investigated with variations in their backbone structures and the state of the amine functionalities on their side chains. Respectively optimized PSCs using the three PEs exhibit different cell-performances, mainly owing to the diode characteristics of built-in potential and recombination strength. To identify how such deviated device-performances correlate with the structural features of PEs, the modulated interfaces of ITO/PEs and PEs/active layer are studied in detail. It is found that conjugated backbones and larger counter-anions on side chains can promote the modulation of ITO work functions (WFs) and that a large amount of protonated amines on PEs is beneficial for junction properties with a subsequent active layer. Additionally, our results indicate that interfacial dipole and electrical doping between the PE and active layer, in addition to WF modulation of the ITO cathode, are important for device efficiency. Accordingly, with the aid of the molecular features of PEIE, PEIE-PSCs exhibit excellent device efficiency and stability compared with PFN- and WPF-PSCs. In the PTB7-th:PC71BM system, a remarkable power-conversion efficiency of 9.97% is achieved with a single PEIE ETL.
Display omitted
•Chemical structure and performance of polyelectrolytes (PEs) in PSCs are correlated.•Interfacial dipole and doping between PEs and active layer lead to efficient PSCs.•PEIE-based PSCs have excellent device efficiency and high stability.•Especially, in the PTB7-th system, encouraging efficiency of 9.97% is achieved.
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