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Perovskite light-emitting diodes (PeLEDs) based on three-dimensional (3D) polycrystalline perovskites suffer from ion migration, which causes overshoot of luminance over time during operation and reduces its operational lifetime. Here, we demonstrate 3D/2D hybrid PeLEDs with extremely reduced luminance overshoot and 21 times longer operational lifetime than 3D PeLEDs. The luminance overshoot ratio of 3D/2D hybrid PeLED is only 7.4% which is greatly lower than that of 3D PeLED (150.4%). The 3D/2D hybrid perovskite is obtained by adding a small amount of neutral benzylamine to methylammonium lead bromide, which induces a proton transfer from methylammonium to benzylamine and enables crystallization of 2D perovskite without destroying the 3D phase. Benzylammonium in the perovskite lattice suppresses formation of deep-trap states and ion migration, thereby enhances both operating stability and luminous efficiency based on its retardation effect in reorientation., Ion migration can induce overshoot of luminance in normal 3D perovskite light-emitting diode devices and results in reduced lifetime. Here Kim et al. show that the ion migration and overshoot can be suppressed in 3D/2D hybrid perovskites, leading to 21 times longer operational lifetime.

MMAE is a potent antimitotic drug used as payload of an antibody-drug conjugate which shows potent activity in preclinical and clinical studies against a range of lymphomas, leukemia and solid tumors. Liquid chromatography-high resolution mass spectrometric method was developed for the quantification of MMAE and its preclinical pharmacokinetics. The method consisted of protein precipitation using acetonitrile (ACN) for sample preparation and liquid chromatography - quadrupole - time-of-flight - tandem mass spectrometry (LC-qTOF-MS/MS) analysis in the positive ion mode. A quadratic regression (weighted 1/concentration2 ), with an equation y = ax2 + bx + c, was used to fit calibration curves over the concentration range of 1.01-2,200 ng/mL for MMAE. The qualification run met the acceptance criteria of ±25% accuracy and precision values for QC samples. Recovery was 42.84%. The dilution integrity was determined for 5-fold dilution and the accuracy and precision ranged within ±25%. The stability results indicated that MMAE was stable for the following conditions: short-term (4 h), long-term (4 weeks), freeze/thaw (3 cycles) and post-preparative stability (12 h). This qualified method was successfully applied to a pharmacokinetic study of MMAE in rat as a preclinical animal model. The PK results suggest that MMAE has moderate CL and low BA.Also, these results would be helpful in having a comprehensive understanding of the PK characteristics of MMAE and developing ADC in future.

5-Amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c) pyrimidine (SCH 58261) is one of the new chemical entities that has been developed as an adenosine A2A receptor antagonist. Although SCH 58261 has been reported to be beneficial, there is little information about SCH 58261 from a drug metabolism or pharmacokinetics perspective. This study describes the metabolism and pharmacokinetic properties of SCH 58261 in order to understand its behaviors in vivo. Rats were used as the in vivo model species. First, an LC&ndash, MS/MS method was developed for the determination of SCH 58261 in rat plasma. A GastroPlus&trade, simulation, in vitro microsomal metabolic stability, and bile duct-cannulated studies were also performed to understand its pharmacokinetic profile. The parameter sensitivity analysis of GastroPlus&trade, was used to examine the factors that influence exposure when the drug is orally administered. The factors are as follows: permeability, systemic clearance, renal clearance, and liver first-pass effect. In vitro microsomal metabolic stability indicates how much the drug is metabolized. The extrapolated hepatic clearance value of SCH 58261 was 39.97 mL/min/kg, indicating that the drug is greatly affected by hepatic metabolism. In vitro microsomal metabolite identification studies revealed that metabolites produce oxidized and ketone-formed metabolites via metabolic enzymes in the liver. The bile duct-cannulated rat study, after oral administration of SCH 58261, showed that a significant amount of the drug was excreted in feces. These results imply that the drug is not absorbed well in the body after oral administration. Taken together, SCH 58261 showed quite a low bioavailability when administered orally and this was likely due to significantly limited absorption, as well as high metabolism in vivo.

Background/aim Many cases of bone damage are due to trauma and metabolic diseases. This study aimed to evaluate bone regeneration into a porous hydroxyapatite (HA) scaffold using dexamethasone (DM)-loaded polymeric microspheres. Materials and methods Four adult dogs were used to evaluate the in vivo performance of DM-loaded microspheres immobilized on the surfaces of porous HA scaffolds. Two 5-mm drill holes were created in both the left and right femurs of each dog. The experimental groups included a control group (drill holes filled with HA scaffold alone), a DM 20 group (holes filled with DM-loaded HA scaffold with 20 mg DM per scaffold), and a DM 100 group (hole filled with DM-loaded HA scaffold with 100 mg DM per scaffold). Resulting bone volume percentages and bone mineral densities were calculated by examing micro-computed tomographic (CT) images. Results The DM-loaded HA scaffold groups showed a gradual periosteal reaction two weeks after insertion of the HA scaffold into the femoral drill holes. Four weeks after HA scaffold insertion, the periosteal reaction in the femoral drill holes became denser. Eight weeks after insertion of DM-loaded HA scaffolds, clear images of the scaffold were observed in micro-CT images of the femoral drill hole. The DM 100 group had better bone healing tendencies (bone mineral density, bone mass, trabecular volume, bone surface, and trabecular thickness) than the DM 20 group. Conclusion DM-loaded HA scaffolds are suitable platforms for distributing bioactive molecules during osteogenesis in femoral drill holes.

Obesity is associated with an increase in adipose tissue, which is mediated by hyperplasia and hypertrophy. Therefore, inhibiting cell proliferation during mitotic clonal expansion (MCE) is one of the major strategies for preventing obesity. The antagonistic effects of Garcinia cambogia (G. cambogia) on obesity have been studied in animal experimental models. However, the effects of G. cambogia extract on MCE, and the underlying molecular mechanisms, are poorly understood. In this study, 3T3-L1 cells were used to investigate whether G. cambogia extract affected cell proliferation during MCE and to identify target molecules for any anti-adipogenic activity. G. cambogia extract suppressed isobutylmethylxanthine and dexamethasone-and-insulin (MDI)-induced adipogenesis at an early stage by attenuating MCE. In G. cambogia extract-treated preadipocytes, MDI-induced cell proliferation and cell cycle progression were inhibited by G0 /G1 arrest due to an increase in p21 and p27 expression, and inhibition of cyclin-dependent kinase 2, cyclin E1 expression, and retinoblastoma (Rb) phosphorylation. In addition, the MDI-induced phosphorylation and subsequent translocation into the nucleus of p90 ribosomal S6 kinase (p90RSK) and signal transducer and activator of transcription (Stat) 3 were suppressed. Specific inhibitors of p90RSK (FMK) and Stat3 (stattic) regulated cell proliferation and adipogenesis. In conclusion, this study demonstrated that G. cambogia extract inhibited MCE by regulating p90RSK, Stat3, and cell cycle proteins, leading to G0 /G1 arrest. These findings provide new insight into the mechanism by which G. cambogia suppresses adipocyte differentiation and show that p90RSK is critical for adipogenesis as a new molecular target.

Precise photothermal cancer therapy still relies on the development of multifunctional theranostic agents to integrate tumor-specific targeting, imaging, and therapy. In this study, we identified the zwitterionic near-infrared (NIR) fluorophore ZW800-Cl, an analog of the well-known ZW800-1, and found that it preferentially accumulated in tumors in various xenograft models. We have demonstrated that the optical and physicochemical properties of ZW800-Cl are similar to those of ZW800-1, but it has a unique tumor targetability. Since ZW800-Cl showed binding selectivity to cancer cells in vitro, it could be specifically targeted to xenograft models of multiple tumor types, including MCF-7, NCI-H460, and HT-29. The in vivo results of photothermal cancer therapy indicated that the xenograft tumors could be effectively ablated by the combination of ZW800-Cl and an 808 nm laser irradiation. In this regard, our finding may provide a new approach for developing multifunctional cancer theranostic agents, setting them apart from conventional nanoparticles based on inorganic and polymeric materials. Therefore, ZW800-Cl may hold promise as a multifunctional theranostic agent for tumor-targeted imaging and effective photothermal cancer therapy.

Parkinson&rsquo, s disease is one of the most common neurodegenerative diseases. Adenosine regulates the response to other neurotransmitters in the brain regions related to motor function. In the several subtypes of adenosine receptors, especially, adenosine 2A receptors (A2ARs) are involved in neurodegenerative conditions. ZM241385 is one of the selective non-xanthine A2AR antagonists with high affinity in the nanomolar range. This study describes the in vitro and in vivo pharmacokinetic properties of ZM241385 in rats. A liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qToF MS) method was developed for the determination of ZM241385 in rat plasma. In vivo IV administration studies showed that ZM241385 was rapidly eliminated in rats. However, the result of in vitro metabolic stability studies showed that ZM241385 had moderate clearance, suggesting that there is an extra clearance pathway in addition to hepatic clearance. In addition, in vivo PO administration studies demonstrated that ZM241385 had low exposure in rats. The results of semi-mass balance studies and the in silico PBPK modeling studies suggested that the low bioavailability of ZM241385 after oral administration in rats was due to the metabolism and by liver, kidney, and gut.

The magnetic exchange interaction is one of the key factors governing the basic characteristics of magnetic systems. In contrast to the symmetric nature of the Heisenberg exchange interaction, the interfacial Dzyaloshinskii-Moriya interaction (DMI) generates an antisymmetric exchange interaction, which offers challenging opportunities in spintronics with intriguing antisymmetric phenomena. The role of the DMI, however, is still under debate, because largely distinct strengths of the DMI have been measured for different magnetic objects, particularly chiral magnetic domain walls (DWs) and nonreciprocal spin waves (SWs). In this paper, by carefully examining the measurement principles, we demonstrate that both the DWs and SWs experience the same strength of the DMI. The key factor in this demonstration is to identify the appropriate experimental conditions by excluding all possible artifacts that causes additional undesired symmetric and antisymmetric contributions in chiral DW dynamics. The present demonstration, therefore, verifies the universality of the DMI between different magnetic dynamics as an intrinsic exchange interaction and also, guarantees the compatibility of several DMI-measurement schemes recently proposed.

Objective To investigate changes of cardiac and muscle damage markers in exercise-induced hypertension (EIH) runners before running (pre-race), immediately after completing a 100-km ultramarathon race, and during the recovery period (24, 72, and 120 hours post-race). Methods In this observational study, volunteers were divided into EIH group (n=11) whose maximum systolic blood pressure was ≥210 mmHg in graded exercise testing and normal exercise blood pressure response (NEBPR) group (n=11). Their blood samples were collected at pre-race, immediately after race, and at 24, 72, and 120 hours post-race. Results Creatine kinase (CK) and cardiac troponin I (cTnI) levels were significantly higher in EIH group than those in the NEBPR group immediately after race and at 24 hours post-race (all p

Background Patients with severe preoperative varus deformity have been reported to have high rates of loosening after total knee arthroplasty (TKA), primarily on the tibial side. This study investigated whether a short extension stem for the tibial component in severely varus knees would reduce the failure rate due to loosening on the tibial side. Methods Patients who underwent TKA, performed by a single surgeon using a single implant between November 1998 and January 2009, were retrospectively evaluated. Patients diagnosed with primary osteoarthritis, having a hip-knee-ankle axis greater than varus 8° on preoperative long-film radiographs, and postoperatively followed up for more than 2 years were included. Patients were divided into “stem” and “nonstem” groups, followed by 1:1 propensity score matching according to age, gender, body mass index, preoperative mechanical axis, and postoperative alignment. Tibial loosening rates in the 2 groups were compared. Results The study cohort included 602 patients, divided into “stem” and “nonstem” groups. Propensity score matching yielded 88 pairs of patients. Mean follow-up duration was similar in the stem and nonstem groups (109.22 vs 103.81 months, P = .451). None of the patients in the stem group, compared with 5 in the nonstem group, experienced aseptic loosening. The overall implant survival rate was significantly higher in the stem group than in the nonstem group (P = .0201). Conclusion Using a short extension stem for the tibial component in primary TKA in patients with severe varus deformity greater than 8° may reduce the rate of loosening of the tibial side and increase the longevity of the implant. Level of evidence Level III.

Objectives: B7-H3 and B7-H4 proteins are expressed in breast cancer tissues, but their relationships with respect to tumor immune surveillance and outcomes in breast cancer are not conclusive. Methods: We first examined B7-H3 and B7-H4 mRNA expression in the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. Next, mRNA and protein expression were assessed by RNAscope in situ hybridization (ISH) and immunohistochemistry in 10 pairs of breast cancer and matched normal tissues. Immunohistochemical staining of B7-H3, B7-H4, CD3, and CD8 was performed in tissue microarray slides containing 198 breast cancer samples. Association of B7-H3 and B7-H4 expression with survival was verified using the publicly accessible BreastMark tool. Results: B7-H3 and B7-H4 mRNA expression were significantly higher in breast cancer samples in the TCGA dataset than in normal breast tissues in the GTEx dataset. RNAscope ISH and immunohistochemistry showed that B7-H3 and B7-H4 mRNA and protein appeared to be mainly expressed in cancer cells. Expression of B7-H3 and B7-H4 tended to be associated with low-density scores of stromal tumor-infiltrating lymphocytes (TILs) as well as molecular subtypes. Expressions of B7-H3 and B7-H4 were negatively correlated with stromal CD3+ and CD8+ T cell infiltration density. B7-H3 and B7-H4 expression was not associated with survival, which was verified by BreastMark analysis. Conclusion: Expression levels of B7-H3 and B7-H4 were independent of clinical outcomes of breast cancer. There was an inverse relationship between the expression of B7-H3 and B7-H4 in breast cancer and the density of stromal TILs and CD8+ T lymphocytes. This inverse relationship may represent a promising target in the field of breast cancer immunotherapy.

Purpose Sentinel lymph node biopsy (SLNB) is the standard axillary procedure in early breast cancer patients. In a randomized trial, the survival rates were not different when axillary lymph node dissection (ALND) was omitted in patients with 1 or 2 lymph node metastases who underwent breast conserving surgery. This study aimed to compare the outcomes in patients who underwent total mastectomy (TM) with 1 or 2 metastatic nodes according to the types of axillary surgery. Methods In total, 79,058 patients registered in the Korean Breast Cancer Society database who underwent TM were included in the analysis. The inclusion criteria were history of TM and SLNB, pathologic T stage 1 or 2, clinically negative axillary lymph nodes, 1 or 2 metastatic axillary lymph nodes, no radiation therapy, and no neoadjuvant therapy. We divided the patients into the SLNB only and SLNB + ALND groups. The groups were matched by propensity scores. We retrospectively analyzed the differences in the overall survival (OS) between the 2 groups. Results A total of 883 patients were matched in a 1:4 ratio for the SLNB only and SLNB + ALND groups in the cohort from 1999 to 2014. There were no significant differences in OS between the 2 groups (P = 0.413). Subgroup analysis revealed a significant survival benefit in the SLNB + ALND group in the T2 subgroup (P = 0.013). Conclusion OS did not differ between the 2 groups in early breast cancer patients with 1 or 2 metastatic axillary lymph nodes who underwent TM. Omission of ALND may be considered in selected patients.

Purpose: The welding quality and reducing production cost could be achieved by developing the automatic on-line welding quality monitoring system. However, investigation of welding fault to quantify the welding quality on the horizontal-position welding has been concentrated. Therefore, MD (Mahalanobis Distance) method on the vertical-position welding process by analysing the transform arc voltage and welding current gained from the on-line monitoring system has been applied. Design/methodology/approach: The transformed welding current and arc voltage data were taken from the experiment whereby the data number was 2500 data/s. The prediction of Contact Tip to Work Distance (CTWD) to gain best welding quality using the waveform variations were then taken from the experimental results. MD was employed to quantify the welding quality by analysing the transformed arc voltage and welding current. Finally, the optimal CTWD setting has verified the developed algorithms through additional experiments. Two kinds of experiments has been carried out by changing welding parameters artificially to verify the sensitivity and feasibility of WQ (Welding Quality) based on the concepts of MD and normal distribution. Findings: The results represented that WQ was fully capable of quantifying and qualifying the welding faults for automatic vertical-position welding process. Research limitations/implications: The arc welding process on the vertical-position compared to a horizontal-position welding is much more difficult because the metal transfer is influenced by the gravity force. To solve the problem, a new algorithm to monitor and control the welding fault during the arc welding process has been developed. Furthermore, optimization of welding parameters for the vertical-position welding process was really difficult to use the developed algorithms because they are only useful in selecting stored data and not for evaluating the effect of the variation of welding parameters on the weld ability. Practical implications: The developed algorithm could be achieved the highest welding quality at 15mm CTWD setting which the welding quality is 99.50% for the start section and 99.68% at the middle section. Originality/value: This paper proposed a new algorithm which employed the concepts of MD (Mahalanobis Distance) and normal distribution to describe a good quality welding.

Systemic inflammation in breast cancer correlates with poor prognosis, but the molecular underpinnings of this connection are not well understood. In this study, we explored the relationship between HER2 overexpression, inflammation, and expansion of the mammary stem/progenitor and cancer stem–like cell (CSC) population in breast cancer. HER2-positive epithelial cells initiated and sustained an inflammatory milieu needed to promote tumorigenesis. HER2 induced a feedforward activation loop of IL1α and IL6 that stimulated NFκB and STAT3 pathways for generation and maintenance of breast CSC. In mice, Il1a genetic deficiency delayed MMTV-Her2–induced tumorigenesis and reduced inflammatory cytokine expression as well as CSC in primary tumors. In clinical specimens of human breast tumor tissues, tissue microarray analysis revealed a strong positive correlation between IL1α/IL6 expression and CSC-positive phenotype. Pharmacologic blockade of IL1α signaling reduced the CSC population and improved chemotherapeutic efficacy. Our findings suggest new therapeutic or prevention strategies for HER2-positive breast cancers. Significance: IL1α signaling driven by HER2 promotes chronic inflammation needed to support cancer stem-like cell maintenance in HER2-positive breast cancers. Cancer Res; 78(8); 2040–51. ©2018 AACR.

Purpose: Since the welding automations have widely been required for industries and engineering, the development of the predicted model has become more important for the increased demands for the automatic welding systems where a poor welding quality becomes apparent if the welding parameters are not controlled. The automated welding system must be modelling and controlling the changes in weld characteristics and produced the output that is in some way related to the change being detected as welding quality. To be acceptable a weld quality must be positioned accurately with respect to the joints, have good appearance with sufficient penetration and reduce low porosity and inclusion content. Design/methodology/approach: To achieve the objectives, two intelligent models involving the use of a neural network algorithm in arc welding process with the help of a numerical analysis program MATLAB have been developed. Findings: The results represented that welding quality was fully capable of quantifying and qualifying the welding faults. Research limitations/implications: Welding parameters in the arc welding process should be well established and categorized for development of the automatic welding system. Furthermore, typical characteristics of welding quality are the bead geometry, composition, microstructure and appearance. However, an intelligent algorithm that predicts the optimal bead geometry and accomplishes the desired mechanical properties of the weldment in the robotic GMA (Gas Metal Arc) welding should be required. The developed algorithm should expand a wide range of material thicknesses and be applicable in all welding position for arc welding process. Furthermore, the model must be available in the form of mathematical equations for the automatic welding system. Practical implications: The neural network models which called BP (Back Propagation) and LM (Levenberg-Marquardt) neural networks to predict optimal welding parameters on the required bead reinforcement area in lab joint in the robotic GMA welding process have been developed. Experimental results have been employed to find the optimal algorithm to predict bead reinforcement area by BP and LM neural networks in lab joint in the robotic GMA welding. The developed intelligent models can be estimated the optimal welding parameters on the desired bead reinforcement area and weld criteria, establish guidelines and criteria for the most effective joint design for the robotic arc welding process. Originality/value: In this study, intelligent models, which employed the neural network algorithms, one of AI (Artificial Intelligence) technologies have been developed to study the effects of welding parameters on bead reinforcement area and to predict the optimal bead reinforcement area for lab joint in the robotic GMA welding process. BP (Back Propagation) and LM (Levenberg-Marquardt) neural network algorithm have been used to develop the intelligent model.

Purpose Breast cancer is one of the most common malignancies worldwide and the second most common cancer among Korean women. The prognosis of breast cancer is poor in patients with other primary cancers. However, there have been few clinical studies regarding this issue. Therefore, we analyzed the characteristics and prognosis of patients with breast cancer with multiple primary cancers (MPCs). Methods Data from the Korean Breast Cancer Society Registry were analyzed. Data from enrolled patients who underwent surgery for breast cancer were analyzed for differences in prognosis dependent on the presence of MPCs, and which MPC characteristics affected their prognosis. Results Among the 41,841 patients analyzed, 913 patients were found to have MPCs, accounting for 950 total MPCs. There was a significant difference in survival rates between the breast cancer only group and the MPC group. The 5-year survival rates were 93.6% and 86.7% and the 10-year survival rates were 87.5% and 70.4%, respectively. Among the 913 patients with MPCs, patients with two or more MPCs had significantly worse prognoses than patients with a single MPC. With respect to the time interval between breast cancer and MPC occurrence, patients with a 5-year or greater interval had significantly better prognoses than patients with less than 1 year between occurrences. Among MPCs, thyroid cancer was the most common primary cancer. However, this type was not related to the prognosis of breast cancer. Gynecologic cancer, colorectal cancer, upper gastrointestinal cancer, and lung cancer were related to breast cancer prognosis. Conclusion MPCs were a poor prognostic factor for patients with breast cancer. Two or more MPCs and a shorter time interval between occurrences were worse prognostic factors. Although MPCs were a poor prognostic factor, thyroid cancer did not affect the prognosis of patients with breast cancer.

Background/Aim: The purpose of this study was to explore the effect of platelet-rich plasma (PRP) on enhancing healing of trachea allotransplantation and confirm the effect via parallel histological and tracheoscopic examinations in seven adult New Zealand White rabbits. Materials and Methods: Harvested trachea was inserted into recipients with end-to-end anastomosis by a simple interrupted suture. PRP-treated rabbits were treated with 0.5 ml of PRP at the trachea grafts, while control rabbit allografts were treated with 0.5 ml of saline. Results: Tracheoscopy of tracheal allografts treated with PRP revealed that the trachea was well healed with no stenosis. The healing effect in the PRP-treated rabbits increased tracheal activity and produced faster trachea regeneration compared to that in control rabbits. There was a good correlation between the subjective symptom of noisy breathing and the objective grading of tracheal stenosis. The tracheal allografts with suture materials appeared slightly pale and looked more like mucosa erosion than normal mucosa at four weeks post-surgery. Contact of trachea-to-transplanted grafts in PRP-treated rabbits was intimate with the surface of the transplanted region and showed high-density epithelialization. After 8 weeks, blood vessels were observed in the transplanted graft in PRP-treated rabbits. Normal epithelium was present in grafts at 8 weeks after allotransplantation. No CD20(+) cells were detected in grafts but a few CD3(+) cells were observed under the epithelium. Conclusion: The results of this study show that it is possible to perform tracheal reconstruction in rabbits treated with PRP after tracheal transplantation

Trastuzumab emtansine (T-DM1, brand name: Kadcyla®) is the first FDA-approved antibody-drug conjugate (ADC) for metastatic human epidermal growth factor receptor 2 positive (HER2+) breast cancer. It consists of three components: trastuzumab, an anti-HER2 monoclonal antibody, maytansinoid (DM1) as a cytotoxic drug, and maleimidomethyl cyclohexane-1-carboxylate (MCC) as a linker. In particular, the MCC linker is known as a non-cleavable linker and has a feature of being conjugated to DM1 by a covalent thioether bond. In this study, we developed an immuno-affinity capture liquid chromatography-mass spectrometric (LC-MS/MS) assay for quantifying the antibody-conjugated drug (acDrug) component of T-DM1. To quantify acDrug, desulfurated DM1 was prepared using a chemical desulfuration pretreatment and quantified as an acDrug. A quadratic regression (weighted 1/concentration), with equation y = ax2 + bx + c, was used to fit the calibration curves over the concentration range of 17.09~1709.44 ng/mL for the acDrug of T-DM1. The quantification run met the in-house acceptance criteria of ±25% accuracy and precision values for the quality control (QC) samples. In conclusion, an immuno-affinity capture LC-MS/MS assay was successfully developed to quantify acDrug of T-DM1 and applied to evaluate in vitro plasma linker stability and preclinical pharmacokinetic (PK) study in rats. This assay could be helpful when applied to other ADCs with the same linker-cytotoxic drug platform.

ZW800-1, a representative zwitterionic near-infrared (NIR) fluorophore, can minimize background tissue uptake owing to its balanced surface charges, and therefore, is widely used for improved NIR fluorescence imaging. As ZW800-1 has no tumor targetability, tumor imaging is highly dependent on the ability of the molecules conjugated to the ZW800-1. To enable tumor targeting using ZW800-1 without additional conjugation, we developed a tumor-targetable and renal-clearable ZW800-1 analog (ZW800-AM) based on the structural modification of ZW800-1. Specifically, an amine group on the center linker of the ZW800-1 indocyanine backbone was modified by replacing phenoxypropionic acid with tyramine linkage on the meso-chlorine atom. This modification improved the tumor targeting ability, which is known as the structure-inherent targeting strategy. More importantly, ZW800-AM not only showed sufficient tumor accumulation without nonspecific uptake but also produced a photothermal effect, killing tumor cells under 808 nm NIR laser irradiation. In addition, ZW800-AM exhibited rapid renal elimination from the body within 4 h of injection, similar to ZW800-1. Overall, the discovery of ZW800-AM as a bifunctional phototherapeutic agent may provide an ideal alternative for tumor-targeted imaging and phototherapy.

Organic-inorganic halide perovskite light emitting diode (PeLED) as a narrow band emitter is an emerging research field. To overcome limited electroluminescence efficiency of PeLEDs, trap-assisted non-radiative recombination in polycrystalline perovskite films should be reduced and the electron-hole balance in the PeLEDs must be improved. In this work, we investigated a practical way to effectively overcome above-mentioned issues by unravelling additive-based nanocrystal pinning (A-NCP) process using the carefully controlled electron transporting organic material solutions diluted in a volatile non-polar solvent. We found that without affecting the intrinsic crystal structure, A-NCP improved the radiative recombination rate by reducing effective defect density at grain boundaries due to the defect healing effect. Moreover, it induced the improved electron-hole balance in the dominantly p-type CH3NH3PbBr3 based PeLEDs, leading to the highest efficiency of 8.79% ever reported to date among organic-inorganic halide perovskite-based green PeLEDs. Therefore, our work gives the effective approaches for efficient PeLEDs from the investigations of the role of A-NCP incorporating a tiny amount of an electron transporting molecule as an additive to increase radiative recombination rate of polycrystalline perovskite films.

As a result of strengthened sulfur content standards for ship fuel oil in IMO regulations, major domestic and foreign carriers have a high and growing demand for liquefied natural gas (LNG) powered ships and related equipment. For LNG operation in a cryogenic environment, a storage tank and fuel supply system that uses steel with excellent brittleness and fatigue strength is required. Ships that use LNG have a high vulnerability to explosion and fire. For this reason, 9% Ni is typically used, since a ship requires high quality products with special materials and structural technologies that guarantee operability at cryogenic temperatures. However, there is an urgent need for research to derive a uniform welding quality, since high process difficulty and differences in welding quality related to a welder’s skills can cause a deterioration of the weld quality in the 9% Ni steel welding process. For 9% Ni steel, the higher the dilution ratio of the base metal, the lower the strength. In order to secure the required strength, excessive dilution of the base metal should be avoided, and the relationship between dilution ratio and strength should be investigated. According to previous research, if it exceeds 25% it may be lower than the API standard of 363 MPa for hardening welds. Therefore, in this study, the flux cored arc welding process is performed by establishing criteria that can be evaluated based on the SVM method in order to determine the structure of the weld to be cured according to the dilution rate of the base metal. We would like to propose a multipurpose optimization algorithm to ensure uniform quality of 9% Ni steel.

Lithium-rich antiperovskite-type (LiRAP) solid electrolytes have received a great deal of attention due to their high mobile ion occupancy rate and narrow activation barrier. Oxide-based LiRAPs are widely studied. However, almost no reports are available on the electrochemical nature of sulfide-based LiRAPs. Here, we prepared the first antiperovskite-like Li3SI – solid solution type solid electrolyte and studied its electrochemical properties. The crystalline nature of the electrolyte was evaluated by powder X-ray diffraction. Electrochemical impedance spectroscopy showed that the Li3SI solid electrolyte exhibited an ionic conductivity of 2.2 × 10−5 S cm−1 at room temperature. The electrochemical stability of the electrolyte was studied with cyclic voltammetry and DC cycle tests, which showed that the proposed electrolyte was stable up to 10 V and >100 h, respectively. An assembled all-solid-state lithium battery using the Li3SI solid electrolyte exhibited an initial discharge capacity of 96.8 mAh g−1 at a current density of 3 mA g−1.

Excessive free fatty acids (FFAs) causes reactive oxygen species (ROS) generation and non-alcoholic fatty liver disease (NAFLD) development. Garcinia cambogia (G. cambogia) is used as an anti-obesity supplement, and its protective potential against NAFLD has been investigated. This study aims to present the therapeutic effects of G. cambogia on NAFLD and reveal underlying mechanisms. High-fat diet (HFD)-fed mice were administered G. cambogia for eight weeks, and steatosis, apoptosis, and biochemical parameters were examined in vivo. FFA-induced HepG2 cells were treated with G. cambogia, and lipid accumulation, apoptosis, ROS level, and signal alterations were examined. The results showed that G. cambogia inhibited HFD-induced steatosis and apoptosis and abrogated abnormalities in serum chemistry. G. cambogia increased in NRF2 nuclear expression and activated antioxidant responsive element (ARE), causing induction of antioxidant gene expression. NRF2 activation inhibited FFA-induced ROS production, which suppressed lipogenic transcription factors, C/EBPα and PPARγ. Moreover, the ability of G. cambogia to inhibit ROS production suppressed apoptosis by normalizing the Bcl-2/BAX ratio and PARP cleavage. Lastly, these therapeutic effects of G. cambogia were due to hydroxycitric acid (HCA). These findings provide new insight into the mechanism by which G. cambogia regulates NAFLD progression.

In this study, solid electrolytes with improved performance are synthesized by mixing Li3SI with an anti-perovskite structure that is stable to lithium metal and Li6PS5Cl with high ionic conductivity. (100–x)Li3SI-xLi6PS5Cl (x = 0, 10, 20, 30), which is a mixture of two sulfide-based solid electrolytes, is prepared by ball milling. The structural characteristics, surface morphology, and particle size of the electrolyte material are analyzed using physico-chemical characterization technologies, such as high-power X-ray diffraction and field emission scanning electron microscopy. Electrochemical impedance spectroscopy is used to calculate the ionic conductivity of the mixed solid electrolyte. The ionic conductivity of 80Li3SI–20Li6PS5Cl, which exhibits the best all-solid-state lithium battery performance, is 5.84 × 10−4 S cm−1. In addition, 80Li3SI–20Li6PS5Cl shows excellent stability against lithium metal. The 2032-type coin cell composed of fabricated Li–In/80Li3SI–20Li6PS5Cl/NCM811 composites shows a superior capacity of 165 mAh g−1 in the initial cycle. This study provides high ionic conductivity and excellent electrochemical performance through the mixing of two kinds of solid electrolyte materials to obtain a promising solid electrolyte.

Biomechanical remodeling of stroma by cancer-associated fibroblasts (CAF) in early stages of cancer is critical for cancer progression, and mechanical cues such as extracellular matrix stiffness control cell differentiation and malignant progression. However, the mechanism by which CAF activation occurs in low stiffness stroma in early stages of cancer is unclear. Here, we investigated the molecular mechanism underlying CAF regulation by SPIN90 and microtubule acetylation under conditions of mechanically soft matrices corresponding to normal stromal rigidity. SPIN90 was downregulated in breast cancer stroma but not tumor, and this low stromal expression correlated with decreased survival in breast cancer patients. Spin90 deficiency facilitated recruitment of mDia2 and APC complex to microtubules, resulting in increased microtubule acetylation. This increased acetylation promoted nuclear localization of YAP, which upregulated expression of myofibroblast marker genes on soft matrices. Spin90 depletion enhanced tumor progression, and blockade of microtubule acetylation in CAF significantly inhibited tumor growth in mice. Together, our data demonstrate that loss of SPIN90-mediated microtubule acetylation is a key step in CAF activation in low stiffness stroma. Moreover, correlation among these factors in human breast cancer tissue supports the clinical relevance of SPIN90 and microtubule acetylation in tumor development. Cancer Res; 77(17); 4710–22. ©2017 AACR.

To study the late cardiac toxicity of breast radiation therapy (RT) in Asian women. Female breast cancer patients in Korea who underwent breast conservation surgery followed by RT from 1990–2012 were identified from two large registries at institution and population levels. Cumulative incidences of acute coronary events (ACE) or cardiac mortality were estimated in relation to the laterality of breast cancer using a competing risks analysis. In an analysis of 2577 women from a single institution, 3.7% were obese (body mass index ≥30), and 3.4% were ever-smokers. Patients with a history of hypertension, diabetes, or coronary artery disease were 17.5, 5.7, and 2.8%, respectively. The mean heart doses were 6.2 and 1.5 Gy for left- and right-sided tumors, respectively. With a median follow-up of 7 (range 1–23) years, the overall and breast cancer-specific survivals at 10 years were 94.9 and 96.5%, respectively. The 10-year cumulative incidence of ACE was 2.96%. The mean time to ACE was 5.2 ± 3.9 years (range 1–17). There was no clinically relevant difference in rates of ACE between left-sided and right-sided patients, with an adjusted hazard ratio of 1.16 (CI 0.59–2.29). An analysis of 24,235 women in a nationwide registry validated these negative findings with respect to cardiac mortality, with an adjusted hazard ratio of 1.52 (CI 0.37–6.25). Increasing age, a higher body mass index, and a history of hypertension or ischemic heart disease were identified as risk factors. Our findings reassure that excess risk from breast RT may be small in healthy women, most of who not smoke, weigh less, and have fewer risk factors. A validation using a larger data set of National Health Insurance Corporation is ongoing.

Real-time personal broadcasting and video social network services on which a user’s mobile device serves as the content provider have received a considerable amount of attention. This letter presents an up-streaming video service in which a mobile device records and encodes video streams on the spot and transmits them to a receiver through an uplink interface. Unlike existing streaming services, the receiver in this service receives and plays video streams in real time without buffering them. Considering the requirements of real-time characteristics and frequent network state changes, this letter proposes a new encoding rate control algorithm for an up-streaming video service based on the estimated network condition. The sender estimates the network status based on the average inter-arrival time of video frames periodically measured and transmitted by the receiver. The network-aware encoding rate control algorithm was implemented on a mobile device running the Android OS. The effectiveness of the algorithm was proved through experiments performed on a commercial LTE network and in an ordinary office WiFi environment.

Microglandular adenosis (MGA) of the breast is a rare, benign proliferative lesion but with a significant rate of associated carcinoma. Herein, we report an unusual case of metaplastic carcinoma with chondroid differentiation associated with typical MGA. Histologically, MGA showed a direct transition to metaplastic carcinoma without an intervening atypical MGA or ductal carcinoma in situ component. The immunohistochemical profile of the metaplastic carcinoma was mostly similar to that of MGA. In both areas, all the epithelial cells were positive for S-100 protein, but negative for estrogen receptor, progesterone receptor, HER2/neu, and epidermal growth factor receptor. An increase in the Ki-67 and p53 labelling index was observed from MGA to invasive carcinoma. To the best of our knowledge, this is the first case of metaplastic carcinoma with chondroid differentiation arising in MGA in Korea. This case supports the hypothesis that a subset of MGA may be a non-obligate morphologic precursor of breast carcinoma, especially the triple-negative subtype.

Recycling uncontaminated excavated construction soil is beneficial because it reduces the costs to abandon excess soil or obtain refill soil from a distant location while alleviating environmental ...

Background/Aim: As an alternative material to the autogenous bone, duck-beak bone particle for bone substitute have been attracting great attention due to their biological properties. To deliver the most favorable outcome of medical treatment, it is essential to study the effect of various processing methods of the duck-beak bone. In this study, we compared the two deproteinizing agents for manufacturing duck-beak bone. Group 1 was treated by a conventional chemical agent (ethylenediamine) and Group 2 by hydrogen dioxide (H2O2). In vitro and in vivo experiments were conducted in parallel to compare the cytocompatibility and osteogenic capability between two processing methods. For in vitro tests, human adipose-derived mesenchymal stem cells (hAD-MSCs) were planted onto each sample and their attachment and growing were evaluated. For in vivo biocompatibility and osteogenic properties, the samples were applied on the critical-sized calvarial bone defect of rats. Group 2 showed significantly higher cell attachment but Group1 showed slightly higher cell proliferation. In in vivo tests, all groups have shown biocompatibility and increased level of osteogenic potential. However, Group 2 had significantly higher bone regeneration (p

Gab-jin Park,1 Soo Hyeon Bae,1 Wan-Su Park,1 Seunghoon Han,1 Min-Ho Park,2 Seok-Ho Shin,2 Young G Shin,2 Dong-Seok Yim1,2 1Department of Clinical Pharmacology and Therapeutics, Seoul St Mary’s Hospital, PIPET (Pharmacometrics Institute for Practical Education and Training), College of Medicine, Catholic University of Korea, Seoul, South Korea; 2College of Pharmacy, Chungnam National University, Daejeon, South Korea Purpose: A microdose drug–drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Patients and methods: Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 µg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2–9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days0, 1, 8, and 9 of both studies for noncompartmental analysis. Results: The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (Cmax) and area under the curve to the last measurement (AUCt) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for Cmax, and 4.07 (micro), 4.33 (regular) for AUCt. For the induction study, they were 0.26 (micro) and 0.21 (regular) for Cmax, and 0.16 (micro) and 0.15 (regular) for AUCt. There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Conclusion: Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes. Keywords: drug–drug interaction, microdose, CYP2C19

Purpose This study investigated the role of the education level (EL) as a prognostic factor for breast cancer and analyzed the relationship between the EL and various confounding factors. Materials and Methods The data for 64,129 primary breast cancer patients from the Korean Breast Cancer Registry were analyzed. The EL was classified into two groups according to the education period; the high EL group (≥ 12 years) and low EL group (< 12 years). Survival analyses were performed with respect to the overall survival between the two groups. Results A high EL conferred a superior prognosis compared to a low EL in the subgroup aged > 50 years (hazard ratio, 0.626; 95% confidence interval [CI], 0.577 to 0.678) but not in the subgroup aged ≤ 50 years (hazard ratio, 0.941; 95% CI, 0.865 to 1.024). The EL was a significant independent factor in the subgroup aged > 50 years according to multivariate analyses. The high EL group showed more favorable clinicopathologic features and a higher proportion of patients in this group received lumpectomy, radiation therapy, and endocrine therapy. In the high EL group, a higher proportion of patients received chemotherapy in the subgroups with unfavorable clinicopathologic features. The EL was a significant prognosticator across all molecular subtypes of breast cancer. Conclusion The EL is a strong independent prognostic factor for breast cancer in the subgroup aged > 50 years regardless of the molecular subtype, but not in the subgroup aged ≤ 50 years. Favorable clinicopathologic features and active treatments can explain the main causality of the superior prognosis in the high EL group.

Generally, heat exchanger is a thermodynamic system which has been employed to transfer thermal energy between two or more fluids, between a solid surface and a fluid, or between solid particulates and a fluid, at different temperatures and in thermal contact. Recently, the growing requirements to save energy and reduce overall environmental impacts has placed greater emphasis on the use of heat exchangers with better thermal efficiency. Therefore, the plate-type heat exchanger that uses metal plates to transfer heat between two fluids has a major advantage over a conventional heat exchanger in which the fluids are exposed to a much larger surface area because the fluids spread out over the plates. However, fouling with the flow of fluid for a long period occurs on the plate surface. So, it might be necessary to carry out numerical simulation for the hot and cold fluid flow model which can reflect the real situation of hot and cold fluid heat transfer. In this paper, plate-type heat exchanger is simulated which based on the computational fluid dynamics method. The calculated model is established for fluid flow and heat transfer in cold and hot flow channels of a chevron-type plate-type heat exchanger. The flow pattern and heat transfer effect of the cold and hot fluids are analyzed under the water-to-water heat transfer by using the simulation software, ANSYS. At the same time, 3D numerical model of the local computation domains for the plate-type heat exchanger are simulated at different parameters which included the corrugated angle, corrugated depth and corrugated pitch. With the development of CFD(Computational Fluid Dynamics) technology, numerical guidance can be provided for the improvement of plate-type heat exchanger and optimization of the design.

Generally, the heat transfer performance of plate-type heat exchanger has been shown lower than other heat exchangers. Recently titanium material that has high formability and performance has been payed attention to a plate material of the plate-type heat exchange. However, the material has a spring-back due to the high strength as well as the mold design for die and punch processes determined by the operator's experience. Furthermore, the factors that affect the sheet forming are too large and complex to describe by mathematical method so that it is quite difficult for the exact design by experimental methods. Since the chevron shape and pattern are important factors in the performance of the plate-type heat exchanger, the heat exchanger that has the same performance with the targeted one has been manufactured in conjunction with mold design. This design has been employed to predict and determine performance of plate-type heat exchanger. If the mold design of the plate-type heat exchanger has considered to the spring-back phenomenon, the design of two-dimensional shape should necessarily be required. Therefore, the compatibility and adequacy of mold design in the plate-type heat exchanger which is used in the industries, can be verified using three-dimensional(3D) Finite Element Method(FEM). In this paper, a forming analysis of a plate-type heat exchanger with its numerical simulation has been carried out. The optimization of mold design in plate-type heat exchanger that has the complex shape has been proposed using the computer simulation. Since the high-tensile steel plate such as Ti material has high stability when designing a metal mold in the new product, an optimization in the quality of plate-type heat exchanger using the developed numerical model has been proposed.

The one of challenging position in the welding process is a vertical-position due to the difficulty. Compared to a horizontal-position, arc welding on the vertical-position is much more difficult because the metal transfer is influenced by the gravity force. Moreover, the gravity force leads to the welding quality decreased that caused by welding fault. To detect the welding fault, the method has still been used based on off-line method which has many disadvantages. One of the disadvantages is the welding fault detection can be performed after the welding process finished. Therefore to deal with this problem, this study is proposed the new algorithm based on Mahalanobis Distance (MD) method for on-line monitoring system. The experimental was carried out with 3 different setting of welding current in order to find out the optimal setting. From the experimental result, it proved that developed algorithm could achieved the highest welding quality at 250A welding current setting which the welding quality is 98.98% for the start section and 98.96% at the middle section. By additional experiment, It was verified that the developed algorithm based on optimized welding current could determine the good quality of weld.

A lot of polymeric oral dosage forms have been invented for suitable drug delivery and compliance of patient. Oral dissolving film (ODF) offers a comfortable way to enable drug administration. The purpose of this study was to develop an ODF using lidocaine, with moderate mechanical strength and thickness, fast disintegration time and local anesthetic effect. Hydroxypropyl methyl cellulose, sodium alginate, glycerin, sodium lauryl sulfate, polyvinylpyrrolidone and citric acid were used to build the polymeric film base of the ODF. The optimal composition was determined by changing the ratio of individual excipients. The thickness was insignificantly varied in the range of 0.04 ± 0.01 to 0.06 ± 0.01 mm. On the other hand, the tensile strength was 1.23 ± 0.20 to 1.83 ± 0.30 N/cm2. Drug content in the films was evaluated and the values were 16 mg of lidocaine per each ODF (40 mg/strip). Lidocaine ODF formulation showed the release of 91.7% of lidocaine within 1 min and 96.3% of lidocaine in 5 min. These results suggested that lidocaine ODF was well prepared and showed the fast release of lidocaine.

Bee venom-loaded poly(lactic-co-glycolic acid) (PLGA) particles were prepared by double emulsion-solvent evaporation, and characterized for a sustained-release system. Factors such as the type of organic solvent, the amount of bee venom and PLGA, the type of PLGA, the type of polyvinyl alcohol, and the emulsification method were considered. Physicochemical properties, including the encapsulation efficiency, drug loading, particle size, zeta-potential and surface morphology were examined by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The size of the bee venom-loaded PLGA particles was 500 nm (measured using sonication). Zeta-potentials of the bee venom-loaded PLGA particles were negative owing to the PLGA. FT-IR results demonstrated that the bee venom was completely encapsulated in the PLGA particles, indicated by the disappearance of the amine and amide peaks. In addition, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis indicated that the bee venom in the bee venom-loaded PLGA particles was intact. In vitro release of the bee venom from the bee venom-loaded PLGA particles showed a sustained-release profile over 1 month. Bee venom-loaded PLGA particles can help improve patients' quality of life by reducing the number of injections required.