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Showing papers by "Yonsei University published in 2012"


Journal ArticleDOI
TL;DR: These guidelines are presented for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes.
Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

4,316 citations


Journal ArticleDOI
TL;DR: A multimodal data set for the analysis of human affective states was presented and a novel method for stimuli selection is proposed using retrieval by affective tags from the last.fm website, video highlight detection, and an online assessment tool.
Abstract: We present a multimodal data set for the analysis of human affective states. The electroencephalogram (EEG) and peripheral physiological signals of 32 participants were recorded as each watched 40 one-minute long excerpts of music videos. Participants rated each video in terms of the levels of arousal, valence, like/dislike, dominance, and familiarity. For 22 of the 32 participants, frontal face video was also recorded. A novel method for stimuli selection is proposed using retrieval by affective tags from the last.fm website, video highlight detection, and an online assessment tool. An extensive analysis of the participants' ratings during the experiment is presented. Correlates between the EEG signal frequencies and the participants' ratings are investigated. Methods and results are presented for single-trial classification of arousal, valence, and like/dislike ratings using the modalities of EEG, peripheral physiological signals, and multimedia content analysis. Finally, decision fusion of the classification results from different modalities is performed. The data set is made publicly available and we encourage other researchers to use it for testing their own affective state estimation methods.

3,013 citations



Journal ArticleDOI
TL;DR: The fabrication of top-gate phototransistors based on a few-layered MoS(2) nanosheet with a transparent gate electrode exhibited excellent photodetection capabilities for red light, while those with single- and double-layers turned out to be quite useful for green light detection.
Abstract: We report on the fabrication of top-gate phototransistors based on a few-layered MoS2 nanosheet with a transparent gate electrode. Our devices with triple MoS2 layers exhibited excellent photodetection capabilities for red light, while those with single- and double-layers turned out to be quite useful for green light detection. The varied functionalities are attributed to energy gap modulation by the number of MoS2 layers. The photoelectric probing on working transistors with the nanosheets demonstrates that single-layer MoS2 has a significant energy bandgap of 1.8 eV, while those of double- and triple-layer MoS2 reduce to 1.65 and 1.35 eV, respectively.

1,247 citations



Journal ArticleDOI
TL;DR: A tractable framework for SINR analysis in downlink heterogeneous cellular networks (HCNs) with flexible cell association policies is developed and the average ergodic rate of the typical user, and the minimum average users throughput - the smallest value among the average user throughputs supported by one cell in each tier is derived.
Abstract: In this paper we develop a tractable framework for SINR analysis in downlink heterogeneous cellular networks (HCNs) with flexible cell association policies. The HCN is modeled as a multi-tier cellular network where each tier's base stations (BSs) are randomly located and have a particular transmit power, path loss exponent, spatial density, and bias towards admitting mobile users. For example, as compared to macrocells, picocells would usually have lower transmit power, higher path loss exponent (lower antennas), higher spatial density (many picocells per macrocell), and a positive bias so that macrocell users are actively encouraged to use the more lightly loaded picocells. In the present paper we implicitly assume all base stations have full queues; future work should relax this. For this model, we derive the outage probability of a typical user in the whole network or a certain tier, which is equivalently the downlink SINR cumulative distribution function. The results are accurate for all SINRs, and their expressions admit quite simple closed-forms in some plausible special cases. We also derive the average ergodic rate of the typical user, and the minimum average user throughput - the smallest value among the average user throughputs supported by one cell in each tier. We observe that neither the number of BSs or tiers changes the outage probability or average ergodic rate in an interference-limited full-loaded HCN with unbiased cell association (no biasing), and observe how biasing alters the various metrics.

1,140 citations


Journal ArticleDOI
TL;DR: New HBV management guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy.
Abstract: Large volume of new data on the natural history and treatment of chronic hepatitis B virus (HBV) infection have become available since 2008. These include further studies in asymptomatic subjects with chronic HBV infection and community-based cohorts, the role of HBV genotype/naturally occurring HBV mutations, the application of non-invasive assessment of hepatic fibrosis and quantitation of HBV surface antigen and new drug or new strategies towards more effective therapy. To update HBV management guidelines, relevant new data were reviewed and assessed by experts from the region, and the significance of the reported findings was discussed and debated. The earlier "Asian-Pacific consensus statement on the management of chronic hepatitis B" was revised accordingly. The key terms used in the statement were also defined. The new guidelines include general management, indications for fibrosis assessment, time to start or stop drug therapy, choice of drug to initiate therapy, when and how to monitor the patients during and after stopping drug therapy. Recommendations on the therapy of patients in special circumstances, including women in childbearing age, patients with antiviral drug resistance, concurrent viral infection, hepatic decompensation, patients receiving immune suppression or chemotherapy and patients in the setting of liver transplantation and hepatocellular carcinoma, are also included.

1,016 citations


Journal ArticleDOI
09 May 2012-JAMA
TL;DR: The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.
Abstract: 2) was reducedfrom8.7%to6.3%.InestimatedGFRof45to59mL/min/1.73m 2 bytheMDRD Study equation, 34.7% of participants were reclassified to estimated GFR of 60 to 89 mL/min/1.73m 2 bytheCKD-EPIequationandhadlowerincidencerates(per1000personyears) for the outcomes of interest (9.9 vs 34.5 for all-cause mortality, 2.7 vs 13.0 for cardiovascular mortality, and 0.5 vs 0.8 for ESRD) compared with those not reclassified. The corresponding adjusted hazard ratios were 0.80 (95% CI, 0.74-0.86) for all-cause mortality, 0.73 (95% CI, 0.65-0.82) for cardiovascular mortality, and 0.49 (95% CI, 0.270.88) for ESRD. Similar findings were observed in other estimated GFR categories by the MDRD Study equation. Net reclassification improvement based on estimated GFR categories was significantly positive for all outcomes (range, 0.06-0.13; all P.001). Net reclassificationimprovementwassimilarlypositiveinmostsubgroupsdefinedbyage(65 years and 65 years), sex, race/ethnicity (white, Asian, and black), and presence or absence of diabetes and hypertension. The results in the high-risk and CKD cohorts were largely consistent with the general population cohorts. Conclusion The CKD-EPI equation classified fewer individuals as having CKD and more accurately categorized the risk for mortality and ESRD than did the MDRD Study equation across a broad range of populations.

855 citations


Journal ArticleDOI
TL;DR: A conductive composite mat of silver nanoparticles and rubber fibres that allows the formation of highly stretchable circuits through a fabrication process that is compatible with any substrate and scalable for large-area applications is introduced.
Abstract: A highly stetchable non-woven mat with printed conductive circuits is fabricated by embedding silver nanoparticles in electrospun fibres.

756 citations


Journal ArticleDOI
TL;DR: A simple solution method is used to prepare emissive hybrid quantum dots consisting of a ZnO core wrapped in a shell of single-layer graphene to make a white-light-emitting diode, and two additional blue emission peaks are observed in the luminescent spectrum of the quantum dot.
Abstract: Quantum dots with a zinc oxide core and a strained graphene shell are used as an emissive layer in a white-light-emitting diode.

639 citations


Journal ArticleDOI
TL;DR: The results suggest that microRNAs can function as signaling molecules and identify TLR7 as an essential element in a pathway that contributes to the spread of CNS damage.
Abstract: Activation of innate immune receptors by host-derived factors exacerbates CNS damage, but the identity of these factors remains elusive. We uncovered an unconventional role for the microRNA let-7, a highly abundant regulator of gene expression in the CNS, in which extracellular let-7 activates the RNA-sensing Toll-like receptor (TLR) 7 and induces neurodegeneration through neuronal TLR7. Cerebrospinal fluid (CSF) from individuals with Alzheimer’s disease contains increased amounts of let-7b, and extracellular introduction of let-7b into the CSF of wild-type mice by intrathecal injection resulted in neurodegeneration. Mice lacking TLR7 were resistant to this neurodegenerative effect, but this susceptibility to let-7 was restored in neurons transfected with TLR7 by intrauterine electroporation of Tlr7(−/−) fetuses. Our results suggest that microRNAs can function as signaling molecules and identify TLR7 as an essential element in a pathway that contributes to the spread of CNS damage.

Journal ArticleDOI
TL;DR: Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis, and this finding suggests that delamanid could enhance treatment options for multi-drug- resistant tuberculosis.
Abstract: Background Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. Methods In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of p...

Journal ArticleDOI
TL;DR: E-ZES+3-month DAPT was noninferior to the standard therapy with respect to the occurrence of the primary endpoint, and the recurrence of any death, myocardial infarction, or stent thrombosis at 1 year was recorded.

Journal ArticleDOI
TL;DR: Somatic inactivation of FAT4 and ARID1A may be key tumorigenic events in a subset of gastric cancers, and cell adhesion was the most enriched biological pathway among the frequently mutated genes.
Abstract: Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcinomas included TP53 (11/15 tumors), PIK3CA (3/15) and ARID1A (3/15). Cell adhesion was the most enriched biological pathway among the frequently mutated genes. A prevalence screening confirmed mutations in FAT4, a cadherin family gene, in 5% of gastric cancers (6/110) and FAT4 genomic deletions in 4% (3/83) of gastric tumors. Frequent mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) also occurred in 47% of the gastric cancers. We detected ARID1A mutations in 8% of tumors (9/110), which were associated with concurrent PIK3CA mutations and microsatellite instability. In functional assays, we observed both FAT4 and ARID1A to exert tumor-suppressor activity. Somatic inactivation of FAT4 and ARID1A may thus be key tumorigenic events in a subset of gastric cancers.

Journal ArticleDOI
01 May 2012-Gut
TL;DR: The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%).
Abstract: Objective Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers. Design Using high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated. Results 22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets ( FGFR2 , ERBB2 ) and also novel genes in gastric cancer ( KLF5 , GATA6 ). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with KRAS gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. FGFR2 -amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype-specific therapy for FGFR2 -amplified gastric cancers. Conclusion The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies.

Journal ArticleDOI
14 Jun 2012-Nature
TL;DR: It is shown that Shank2-mutant (Shank2−/−) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping.
Abstract: Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.

Journal ArticleDOI
TL;DR: The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined and the optimal duration for 6-and 12-month DAPT has not been determined as mentioned in this paper.
Abstract: Background—The optimal duration of dual antiplatelet therapy (DAPT) after implantation of drug-eluting coronary stents remains undetermined. We aimed to test whether 6-month DAPT would be noninferior to 12-month DAPT after implantation of drug-eluting stents. Methods and Results—We randomly assigned 1443 patients undergoing implantation of drug-eluting stents to receive 6- or 12-month DAPT (in a 1:1 ratio). The primary end point was a target vessel failure, defined as the composite of cardiac death, myocardial infarction, or ischemia-driven target vessel revascularization at 12 months. Rates of target vessel failure at 12 months were 4.8% in the 6-month DAPT group and 4.3% in the 12-month DAPT group (the upper limit of 1-sided 95% confidence interval, 2.4%; P=0.001 for noninferiority with a predefined noninferiority margin of 4.0%). Although stent thrombosis tended to occur more frequently in the 6-month DAPT group than in the 12-month group (0.9% versus 0.1%; hazard ratio, 6.02; 95% confidence interval, ...

Journal ArticleDOI
15 Aug 2012-ACS Nano
TL;DR: In this paper, size-dependent shape/edge-state variations of GQDs and visible photoluminescence (PL) showing anomalous size dependences were investigated.
Abstract: For the application of graphene quantum dots (GQDs) to optoelectronic nanodevices, it is of critical importance to understand the mechanisms which result in novel phenomena of their light absorption/emission. Here, we present size-dependent shape/edge-state variations of GQDs and visible photoluminescence (PL) showing anomalous size dependences. With varying the average size (da) of GQDs from 5 to 35 nm, the peak energy of the absorption spectra monotonically decreases, while that of the visible PL spectra unusually shows nonmonotonic behaviors having a minimum at da = ∼17 nm. The PL behaviors can be attributed to the novel feature of GQDs, that is, the circular-to-polygonal-shape and corresponding edge-state variations of GQDs at da = ∼17 nm as the GQD size increases, as demonstrated by high-resolution transmission electron microscopy.


Journal ArticleDOI
A.E. Bondar1, A. Garmash1, R. Mizuk, D. Santel2  +154 moreInstitutions (46)
TL;DR: The observation of two narrow structures in the mass spectra of the π(±)Υ(nS) and π (±)h(b)(mP) pairs that are produced in association with a single charged pion in Υ(5S) decays is reported.
Abstract: We report the observation of two narrow structures in the mass spectra of the pi(+/-) Y(nS) (n = 1, 2, 3) and pi(+/-) h(b)(mP) (m = 1, 2) pairs that are produced in association with a single charged pion in Y(5S) decays The measured masses and widths of the two structures averaged over the five final states are M-1 = (10 6072 +/- 20) MeV/c(2), Gamma(1) =(184 +/- 24) MeV, and M-2 = (10 6522 +/- 15) MeV/c(2), Gamma(2) = (115 +/- 22) MeV The results are obtained with a 1214 fb(-1) data sample collected with the Belle detector in the vicinity of the Y(5S) resonance at the KEKB asymmetric-energy e(+)e(-) collider

Journal ArticleDOI
TL;DR: AtABCC1 and AtABCC2 are important vacuolar transporters that confer tolerance to cadmium and mercury, in addition to their role in arsenic detoxification, which provide useful tools for genetic engineering of plants with enhanced metal tolerance and accumulation, which are desirable characteristics for phytoremediation.
Abstract: Heavy metals such as cadmium (Cd) and mercury (Hg) are toxic pollutants that are detrimental to living organisms. Plants employ a two-step mechanism to detoxify toxic ions. First, phytochelatins bind to the toxic ion, and then the metal-phytochelatin complex is sequestered in the vacuole. Two ABCC-type transporters, AtABCC1 and AtABCC2, that play a key role in arsenic detoxification, have recently been identified in Arabidopsis thaliana. However, it is unclear whether these transporters are also implicated in phytochelatin-dependent detoxification of other heavy metals such as Cd(II) and Hg(II). Here, we show that atabcc1 single or atabcc1 atabcc2 double knockout mutants exhibit a hypersensitive phenotype in the presence of Cd(II) and Hg(II). Microscopic analysis using a Cd-sensitive probe revealed that Cd is mostly located in the cytosol of protoplasts of the double mutant, whereas it occurs mainly in the vacuole of wild-type cells. This suggests that the two ABCC transporters are important for vacuolar sequestration of Cd. Heterologous expression of the transporters in Saccharomyces cerevisiae confirmed their role in heavy metal tolerance. Over-expression of AtABCC1 in Arabidopsis resulted in enhanced Cd(II) tolerance and accumulation. Together, these results demonstrate that AtABCC1 and AtABCC2 are important vacuolar transporters that confer tolerance to cadmium and mercury, in addition to their role in arsenic detoxification. These transporters provide useful tools for genetic engineering of plants with enhanced metal tolerance and accumulation, which are desirable characteristics for phytoremediation.

Journal ArticleDOI
TL;DR: Perceived trust exerted a stronger effect than perceived price on purchase intentions for both potential and repeat customers of an online store and that of repeat customers as compared to that of potential customers.

Journal ArticleDOI
TL;DR: Although no significant difference in progression-free survival was noted between groups, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma.
Abstract: Summary Background Combination chemotherapy with gemcitabine and a platinum-based agent is regarded as a standard treatment for patients with advanced biliary-tract cancer. Results of phase 2 trials of single-agent erlotinib in biliary-tract cancer and of gemcitabine plus erlotinib in pancreatic cancer have shown modest benefits. Therefore, we aimed to investigate the efficacy of gemcitabine and oxaliplatin plus erlotinib versus chemotherapy alone for advanced biliary-tract cancer. Methods In this open label, randomised, phase 3 trial, we randomly assigned patients (in a 1:1 ratio) with metastatic biliary-tract cancer (cholangiocarcinoma, gallbladder cancer, or ampulla of Vater cancer) to receive either first-line treatment with chemotherapy alone (gemcitabine 1000 mg/m 2 on day 1 and oxaliplatin 100 mg/m 2 on day 2) or chemotherapy plus erlotinib (100 mg daily). Treatment was repeated every 2 weeks until disease progression or unacceptable toxic effects. Randomisation was done centrally (stratified by participating centre and presence of measurable lesion). The primary endpoint was progression-free survival. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT01149122. Findings 133 patients were randomly assigned to the chemotherapy alone group and 135 to the chemotherapy plus erlotinib group. The groups were balanced except for a higher proportion of patients with cholangiocarcinoma in the group given erlotinib than in the chemotherapy alone group (96 [71%] patients vs 84 [63%]). Median progression-free survival was 4·2 months (95% CI 2·7–5·7) in the chemotherapy alone group and 5·8 months (95% CI 4·6–7·0) in the chemotherapy plus erlotinib group (hazard ratio [HR] 0·80, 95% CI 0·61–1·03; p=0·087). Significantly more patients had an objective response in the chemotherapy plus erlotinib group than in the chemotherapy alone group (40 patients vs 21 patients; p=0·005), but median overall survival was the same in both groups (9·5 months [95% CI 7·5–11·5] in the chemotherapy alone group and 9·5 months [7·6–11·4] in the chemotherapy plus erlotinib group; HR 0·93, 0·69–1·25; p=0·611). All-cause deaths within 30 days of random assignment occurred in one (1%) of the patients in the chemotherapy alone group and in four (3%) of those in the chemotherapy plus erlotinib group. The most common grade 3–4 adverse event was febrile neutropenia (eight [6%] patients in the chemotherapy alone group and six [4%] in the chemotherapy plus erlotinib group). No patient died of treatment-related causes during the study. Subgroup analyses by primary site of disease showed that for patients with cholangiocarcinoma, the addition of erlotinib to chemotherapy significantly prolonged median progression-free survival (5·9 months [95% CI 4·7–7·1] for chemotherapy plus erlotinib vs 3·0 months [1·1–4·9] for chemotherapy alone; HR 0·73, 95% CI 0·53–1·00; p=0·049). Interpretation Although no significant difference in progression-free survival was noted between groups, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma. Funding None.

Journal ArticleDOI
TL;DR: It is visualize that cube has higher magnetization value than sphere with highest coercivity at 60 nm, and its hybridization into core-shell (CS) structure brings about a 14-fold increase in the coercivity with an exceptional energy conversion of magnetic field into thermal energy, the largest reported to date.
Abstract: With the aim of controlling nanoscale magnetism, we demonstrate an approach encompassing concepts of surface and exchange anisotropy while reflecting size, shape, and structural hybridization of nanoparticles. We visualize that cube has higher magnetization value than sphere with highest coercivity at 60 nm. Its hybridization into core–shell (CS) structure brings about a 14-fold increase in the coercivity with an exceptional energy conversion of magnetic field into thermal energy of 10600 W/g, the largest reported to date. Such capability of the CS-cube is highly effective for drug resistant cancer cell treatment.

Journal ArticleDOI
TL;DR: The potential utility of this probe in indicating pathogenic states and as a possible screening tool for agents that can manipulate oxidative stress was demonstrated in experiments wherein palmitate was used to induce lipotoxicity in HepG2 cells.
Abstract: We present the design, synthesis, spectroscopic properties, and biological evaluation of a single galactose-appended naphthalimide (1). Probe 1 is a multifunctional molecule that incorporates a thiol-specific cleavable disulfide bond, a masked phthalamide fluorophore, and a single galactose moiety as a hepatocyte-targeting unit. It constitutes a new type of targetable ligand for hepatic thiol imaging in living cells and animals. Confocal microscopic imaging experiments reveal that 1, but not the galactose-free control system 2, is preferentially taken up by HepG2 cells through galactose-targeted, ASGP-R-mediated endocytosis. Probe 1 displays a fluorescence emission feature at 540 nm that is induced by exposure to free endogenous thiols, most notably GSH. The liver-specificity of 1 was confirmed in vivo via use of a rat model. The potential utility of this probe in indicating pathogenic states and as a possible screening tool for agents that can manipulate oxidative stress was demonstrated in experiments wherein palmitate was used to induce lipotoxicity in HepG2 cells.

Journal ArticleDOI
01 Dec 2012-Knee
TL;DR: The short-term results of the study are encouraging and demonstrate that infrapatellar fat pad-derived MSC therapy with intraarticular injections is safe, and provides assistance in reducing pain and improving function in patients with knee OA.
Abstract: Purpose The aim of the study was to determine if isolated mesenchymal stem cells (MSCs) derived from the infrapatellar fat pad could effectively improve clinical results when percutaneously injected into arthritic knees. Level of evidence Therapeutic case–control study; Level III. Methods Twenty five stem cell injections combined with arthroscopic debridement were administered to patients with knee OA. A mean of 1.89×10 6 stem cells were prepared with approximately 3.0mL of platelet-rich plasma (PRP) and injected in the selected knees of patients in the study group. Results The mean Lysholm, Tegner activity scale, and VAS scores of patients in the study group improved significantly by the last follow-up visit. No major adverse events related to the injections were observed during the treatment and follow-up periods. The results were compared between the study and control groups, in which the patients had undergone arthroscopic debridement and PRP injection without stem cells. Although the preoperative mean Lysholm, Tegner activity scale, and VAS scores of the study group were significantly poorer than those of the control group, the clinical results at the last follow-up visit were similar and not significantly different between the two groups. Conclusions The short-term results of our study are encouraging and demonstrate that infrapatellar fat pad-derived MSC therapy with intraarticular injections is safe, and provides assistance in reducing pain and improving function in patients with knee OA.

Journal ArticleDOI
TL;DR: This article provided the first longitudinally designed, classroom-based empirical test of self-determination theory's motivation mediation model, which revealed a complex, dynamic model that unfolds within naturally occurring classroom processes.
Abstract: This study provides the first longitudinally designed, classroom-based empirical test of self-determination theory's motivation mediation model. Measures of perceived autonomy support, motivation (autonomy need satisfaction), engagement, and achievement were collected from 500 (257 females, 243 males) 8th-grade students in Korea in a 3-wave longitudinal research design. Multilevel structural equation modeling tested the model in which early-semester perceived autonomy support increased mid-semester autonomy need satisfaction, which, in turn, increased end-of-the-semester engagement, which then predicted course achievement. We further tested for possible reciprocal pathways and for the stability of all effects throughout the model. Results revealed a complex, dynamic model that unfolds within naturally occurring classroom processes, one that validated the hypothesized model but also extended and qualified it in important ways. All hypothesized effects were supported, but they were not stable over the course of the semester, largely because of the emergence of several reciprocal effects. Overall, this longitudinal test revealed a more dynamic model than suggested by previous cross-sectional investigations.

Journal ArticleDOI
TL;DR: In this paper, the authors summarize the recent developments of superhydrophobic surfaces with unique structural and functional properties, including self-cleaning, icephobicity, anti-corrosion, drag reduction, transparency, antireflection, structural color, droplet transportation, anisotropy, oil-water separation, water supporting force, superamphiphobicity and responsive switching.
Abstract: The surface wettability control of solid materials has been considered as an essential aspect of surface chemistry. In the past decade, superhydrophobic surfaces have revealed a cornucopia of novel structural and functional properties, exhibiting considerable importance in both fundamental research and practical applications. In this review, we summarize the recent developments of superhydrophobic surfaces with unique structural and functional properties. Both the fabricative methods and the working performance of superhydrophobic surfaces with multidisciplinary functionalities including self-cleaning, icephobicity, anti-corrosion, drag reduction, transparency, anti-reflection, structural color, droplet transportation, anisotropy, oil–water separation, water supporting force, superamphiphobicity and responsive switching, have been discussed briefly. Finally, the current challenges and future prospects of this dynamic field are discussed based on our own opinion.

Journal ArticleDOI
TL;DR: In this article, a large collection of porous metal-organic frameworks (MOFs) with the intent of finding correlations between CO2 separation ability and various material properties was investigated, showing clear correlations between purely structural characteristics (e.g., pore size, surface area, and pore volume), as well as chemical characteristics (i.e., functional groups), with five adsorbent evaluation criteria taken from the engineering literature.
Abstract: There is an urgent need to identify porous materials that can efficiently separate CO2 from mixtures of gases, such as the exhaust of fossil-fuel-based power plants and from impure sources of CH4 (e.g., natural gas and landfill gas). Recently, researchers have investigated collections of porous metal–organic frameworks (MOFs) with the intent of finding correlations between CO2 separation ability and various material properties. However, due to the limited size of the collections, no clear correlations were found for material properties such as pore size, surface area, and pore volume, leaving researchers with little guidance in the design of new materials. In this work we drastically expand the scope of previous studies to include over 130000 hypothetical MOFs, using molecular simulation to generate the adsorption properties. The resulting data exhibit sharply defined structure–property relationships that were not apparent when smaller collections of MOFs were considered. We show clear correlations between purely structural characteristics (e.g., pore size, surface area, and pore volume), as well as chemical characteristics (i.e., functional groups), with five adsorbent evaluation criteria taken from the engineering literature. These reported structure–property relationships can serve as a map for experimental synthesis going forward.

Journal ArticleDOI
TL;DR: The MSC-MV proteome provides a comprehensive basis for understanding the potential of MSC's self-renewal and differentiation-related genes to affect tissue repair and regeneration.
Abstract: Mesenchymal stem cells (MSCs) have emerged as a promising means for treating degenerative or incurable diseases. Recent studies have shown that microvesicles (MVs) from MSCs (MSC-MVs) contribute to recovery of damaged tissues in animal disease models. Here, we profiled the MSC-MV proteome to investigate their therapeutic effects. LC–MS/MS analysis of MSC-MVs identified 730 MV proteins. The MSC-MV proteome included five positive and two variable known markers of MSCs, but no negative marker, as well as 43 surface receptors and signaling molecules controlling self-renewal and differentiation of MSCs. Functional enrichment analysis showed that cellular processes represented by the MSC-MV proteins include cell proliferation, adhesion, migration, and morphogenesis. Integration of MSC’s self-renewal and differentiation-related genes and the proteome of MSC-conditioned media (MSC-CM) with the MSC-MV proteome revealed potential MV protein candidates that can be associated with the therapeutic effects of MSC-MVs: ...