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Phototropin (phot) is a blue light (BL) receptor and thermosensor that mediates chloroplast movements in plants. Liverworts, as early‐diverging plant species, have a single copy of PHOT gene, and the phot protein in each liverwort activates the signaling pathway adapted to its specific growing environment. In this study, we functionally compared phot from two different liverworts species: Apopellia endiviifolia (Aephot) and Marchantia polymorpha (Mpphot). The BL‐dependent photochemical activity of Aephot was similar to that of Mpphot, whereas the thermochemical activity of Aephot was lower than that of Mpphot. Therefore, the phot‐mediated signaling pathways of the two plant species may differ more in response to temperature than to BL. Furthermore, we analyzed the functional compatibility of Aephot and Mpphot in chloroplast movements by transiently expressing AePHOT or MpPHOT. The transient expression of AePHOT did not mediate chloroplast movement in M. polymorpha, showing the incompatibility of Aephot with the signaling pathway of M. polymorpha. By contrast, the transient expression of MpPHOT mediated chloroplast movement in A. endiviifolia, indicating the compatibility of Mpphot with the signaling pathway of A. endiviifolia. Our findings reveal both functional similarities and differences between Aephot and Mpphot proteins from the closely related liverworts. [ABSTRACT FROM AUTHOR]

Chloroplasts move to the periclinal walls of cells under weak light to harness light energy for photosynthesis and to anticlinal walls to avoid strong light. These responses involve the cytoskeleton components microtubules and/or actin filaments. In the dark, chloroplasts move to the anticlinal cell walls bordering neighbouring cells (dark‐positioning response), but this response in various plants normally requires a prolonged dark incubation period, which has hampered analysis. However, we recently demonstrated the dark‐positioning response that can be induced after a short period of dark incubation in the liverwort Apopellia endiviifolia. Here, we investigated whether the cytoskeleton components function in the dark‐positioning response of A. endiviifolia cells. Microtubules and actin filaments were fluorescently visualised in A. endiviifolia cells and were disrupted following treatment with the microtubule and actin filament polymerisation inhibitors. The dark‐positioning response was unaffected in the cells with disrupted microtubules. By contrast, the dark‐positioning response was inhibited by the disruption of actin filaments. The disruption of actin filaments also restricted chloroplast mobility during light‐ and cold‐dependent chloroplast movements in A. endiviifolia. Therefore, the dark‐positioning response of A. endiviifolia depends solely on an actin filament‐associated motility mechanism, as do the light‐ and cold‐dependent chloroplast responses. Summary statement: Dark‐induced chloroplast positioning (dark‐positioning response) in plants has been known to require a prolonged time to complete. Our study shows that a rapid dark‐positioning response occurs in the liverwort Apopellia endiviifolia and that this response is regulated by the actin filament. [ABSTRACT FROM AUTHOR]

Quantum enhanced multiple phase estimation is essential for various applications in quantum sensors and imaging. For multiple phase estimation, the sensitivity enhancement is dependent on both quantum probe states and measurement. It is known that multi-mode N00N states can outperform other probe states for estimating multiple phases. However, it is generally not feasible in practice to implement an optimal measurement to achieve the quantum Cramer–Rao bound (QCRB) under a practical measurement scheme using a multi-mode beam splitter in interferometric phase estimation. Here, a strategy to achieve the best practical sensitivity by optimizing both mode-amplitudes of multi-mode N00N states and a split ratio of a multi-mode beam splitter is investigated. Then, it is experimentally demonstrated that the best sensitivity is achieved when an amplitude-balanced multi-mode N00N state and a multi-mode beam splitter with an unbalanced ratio are used in three-mode interferometric phase estimation. The results show that the lower QCRB cannot guarantee better sensitivity under a practical measurement scheme, thus it is more desirable to enhance the practical sensitivity rather than the QCRB. It is believed that this strategy can provide a powerful tool for practical applications in multiple phase estimation. [ABSTRACT FROM AUTHOR]

In this study, the conceptual design and performance of a multimodal X-ray probe station recently installed at the 9C coherent X-ray scattering beamline of the Pohang Light Source-II are presented. The purpose of this apparatus is to measure coherent X-ray diffraction, X-ray fluorescence and electrical properties simultaneously. A miniature vacuum probe station equipped with a four-point probe was mounted on a six-axis motion hexapod. This can be used to study the structural and chemical evolution of thin films or nanostructures, as well as device performance including electronic transport properties. This probe station also provides the capability of varying sample environments such as gas atmosphere using a mass-flow-control system and sample temperatures up to 600 °C using a pyrolytic boron nitride heater. The in situ annealing of ZnO thin films and the performance of ZnO nanostructure-based X-ray photodetectors are discussed. These results demonstrate that a multimodal X-ray probe station can be used for performing in situ and operando experiments to investigate structural phase transitions involving electrical resistivity switching. [ABSTRACT FROM AUTHOR]

Interleukin‐33 (IL‐33) is an epithelial‐derived cytokine that plays an important role in immune‐mediated diseases such as asthma, atopic dermatitis, and rheumatoid arthritis. Although IL‐33 is considered a potential target for the treatment of allergy‐related diseases, no small molecule that inhibits IL‐33 has been reported. Based on the structure‐activity relationship and in vitro 2D NMR studies employing 15N‐labeled IL‐33, we identified that the oxazolo[4,5‐c]‐quinolinone analog 7 c binds to the interface region of IL‐33 and IL‐33 receptor (ST2), an orphan receptor of the IL‐1 receptor family. Compound 7 c effectively inhibited the production of IL‐6 in human mast cells in a dose‐dependent manner. Compound 7 c is the first low molecular weight IL‐33 inhibitor and may be used as a prototype molecule for structural optimization and investigation of the IL‐33/ST2 signaling pathway. [ABSTRACT FROM AUTHOR]

Changes in the subcellular localisation of chloroplasts help optimise photosynthetic activity under different environmental conditions. In many plants, this movement is mediated by the blue‐light photoreceptor phototropin. A model organism with simple phototropin signalling that allows clear observation of chloroplasts would facilitate the study of chloroplast relocation movement. Here, we examined this process in the simple thalloid liverwort Apopellia endiviifolia. Transverse sections of the thallus tissue showed uniformly developed chloroplasts and no air chambers; these characteristics enable clear observation of chloroplasts and analysis of their movements under a fluorescence stereomicroscope. At 22°C, the chloroplasts moved to the anticlinal walls of cells next to the neighbouring cells in the dark (dark‐positioning response), whereas they moved towards weak light (accumulation response) and away from strong light (avoidance response). When the temperature was reduced to 5°C, the chloroplasts moved away from weak light (cold‐avoidance response). Hence, both light‐ and temperature‐dependent chloroplast relocation movements occur in A. endiviifolia. Notably, the accumulation, avoidance and cold‐avoidance responses were induced under blue‐light but not under red‐light. These results suggest that phototropin is responsible for chloroplast relocation movement in A. endiviifolia and that the characteristics are similar to those in the model liverwort Marchantia polymorpha. RNA sequencing and Southern blot analysis identified a single copy of the PHOTOTROPIN gene in A. endiviifolia, indicating that a simple phototropin signalling pathway functions in A. endiviifolia. We conclude that A. endiviifolia has great potential as a model system for elucidating the mechanisms of chloroplast relocation movement. [ABSTRACT FROM AUTHOR]

Early oligomerization of human islet amyloid polypeptide (hIAPP), which is accountable for β‐cell death, has been implicated in the progression of type 2 diabetes mellitus. Some researches have shown the connection between hIAPP and Alzheimer's disease as well. However, the mechanism of peptide accumulation and associated cytotoxicity remains unclear. Due to the unique properties and significant role of histidine in protein sequences, here for the first time, the tautomeric effect of histidine at the early stages of amylin misfolding was investigated via molecular dynamics simulations. Considering Tau and Pi tautomeric forms of histidine (Tau and Pi tautomers are denoted as ϵ and δ, respectively), simulations were performed on two possible isomers of amylin. Our analysis revealed a higher probability of transient α‐helix generation in the δ isomer in monomeric form. In dimeric forms, the δδ and δϵ conformations showed an elevated amount of α‐helix and lower coil in comparison to the ϵϵ dimer. Due to the significant role of α‐helix in membrane disruption and transition to β‐sheet structure, these results may imply a noticeable contribution of the δ isomer and the δδ and δϵ dimers rather than ϵ and ϵϵ conformations in the early stages of diabetes initiation. Our results may aid in elucidating the hIAPP self‐association process in the etiology of amyloidosis. [ABSTRACT FROM AUTHOR]

Patient-derived cancer models that reconstitute the characteristics of the tumor microenvironment may facilitate efforts in precision immune-oncology and the discovery of effective anticancer therapies. Organoids that have recently emerged as robust preclinical models typically contain tumor epithelial cells and lack the native tumor immune microenvironment. A patient-derived organotypic tumor spheroid (PDOTS) is a novel and innovative ex vivo system that retains key features of the native tumor immune microenvironment. Here, we established and characterized a series of colorectal cancer PDOTS models for use as a preclinical platform for testing effective immunotherapy and its combinations with other drugs. Partially dissociated (> 100 μm in diameter) tumor tissues were embedded in Matrigel-containing organoid media and subsequently formed into organoid structures within 3 to 7 days of culture. The success rate of growing PDOTS from fresh tissues was ~86%. Morphological analysis showed that the PDOTSs varied in size and structure. Immunofluorescence and flow cytometry analysis revealed that the PDOTSs retained autologous tumor-infiltrating lymphoid cells and tumor-infiltrating lymphoid cells were continually decreased through serial passages. Notably, PDOTSs from tumors from a high-level microsatellite instability-harboring patient were sensitive to anti-PD-1 or anti-PD-L1 antibodies. Our results demonstrate that the PDOTS model in which the tumor immune microenvironment is preserved may represent an advantageous ex vivo system to develop effective immune therapeutics. [ABSTRACT FROM AUTHOR]

The effect of the amount of Hartree-Fock mixing parameter ( α) and of the screening parameter ( w) defining the range separated HSE type hybrid functional is systematically studied for a series of seven metal oxides: TiO2, ZrO2, CuO2, ZnO, MgO, SnO2, and SrTiO3. First, reliable band gap values were determined by comparing the optimal α reproducing the experiment with the inverse of the experimental dielectric constant. Then, the effect of the w in the HSE functional on the calculated band gap was explored in detail. Results evidence the existence of a virtually infinite number of combinations of the two parameters which are able to reproduce the experimental band gap, without a unique pair able to describe the full studied set of materials. Nevertheless, the results point out the possibility of describing the electronic structure of these materials through a functional including a screened HF exchange and an appropriate correlation contribution. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

ABSTRACT A new set of push-pull type 2D-conjugated polymers (P1-P4) were designed and synthesized where A1, A2 (oxygen analogues) and A3, A4 (sulfur analogues) are electron deficient units used as co-monomers. On introduction of new repeating units into the polymer backbone, significant changes were observed in optoelectronic properties. Furthermore, the heteroatom exchange in new repeating units has also brought notable changes in photophysical properties, in particular P1 and P2 (oxygen analogues) showed bathochromic shift in UV-vis absorption spectra and deeper HOMO energy levels than P3, P4 (sulfur analogues). Interestingly P1, P3 absorption spectra shows a vibronic shoulder (659, 652 nm) peak in lower energy region, and this might originated from non-covalent interactions between the electron rich and electron deficient units. In addition, the systematic investigation of these polymers with additive and solvent treatment, yielded in enhanced power conversion efficiency of 4.29% for P3-based devices in bulk heterojunction organic solar cells. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 2668-2679 [ABSTRACT FROM AUTHOR]

ABSTRACT Polymers using new electron-deficient units, 2-pyriminecarbonitrile and 2-fluoropyrimidine, were synthesized and utilized for the photovoltaics. Donor-acceptor (D-A) types of conjugated polymers ( PBDTCN, PBDTTCN, PBDTF, and PBDTTF) containing 4,8- bis(2-octyldodecyloxy)benzo[1,2- b;3,4- b′]dithiophene (BDT) or 4,8- bis(5-(2-octyldodecyloxy)thiophen-2-yl)benzo[1,2- b:4,5- b′]dithiophene (BDTT) as electron rich unit and 2-pyriminecarbonitrile or 2-fluoropyrimidine as electron deficient unit were synthesized. We designed pyrimidine derivatives in which strong electron-withdrawing group (CN or fluorine) was introduced to the C2 position for the generation of strong electron-deficient property. By the combination with the electron-rich unit, the pyrimidines will provide low band gap polymers with low highest occupied molecular orbital (HOMO) energy levels for higher open-circuit voltages ( VOC). For the syntheses of the polymers, the electron-rich and the electron-deficient units were combined by Stille coupling reaction with Pd(0)-catalyst. Absorption spectra of the thin films of PBDTTCN and PBDTTF with BDTT unit show shift to a longer wavelength region than PBDTCN and PBDTF with BDT unit. Four synthesized polymers provided low electrochemical bandgaps of 1.56 to 1.96 eV and deep HOMO energy levels between −5.67 and −5.14 eV. © 2015 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 771-784 [ABSTRACT FROM AUTHOR]

In this paper, we discuss the issues of providing protection for point-to-multipoint connections in both Ethernet and MPLS-TP-based packet transport networks. We introduce two types of per-leaf protection--linear and ring. Neither of the two types requires that modifications to existing standards be made. Their performances can be improved by a collective signal fail mechanism proposed in this paper. In addition, two schemes--tree protection and hybrid protection--are newly proposed to reduce the service recovery time when a single failure leads to multiple signal fail events, which in turn places a significant amount of processing burden upon a root node. The behavior of the tree protection protocol is designed with minimal modifications to existing standards. The hybrid protection scheme is devised to maximize the benefits of per-leaf protection and tree protection. To observe how well each scheme achieves an efficient traffic recovery, we evaluate their performances using a test bed as well as computer simulation based on the formulae found in this paper. [ABSTRACT FROM AUTHOR]

Guanosine triphosphatases (GTPases) function as molecular switches in signal transduction pathways that enable cells to respond to extracellular stimuli. Saccharomyces cerevisiae yeast protein two 1 protein (Ypt1p) is a monomeric small GTPase that is essential for endoplasmic reticulum-to-Golgi trafficking. By size-exclusion chromatography, SDS-PAGE, and native PAGE, followed by immunoblot analysis with an anti-Ypt1p antibody, we found that Ypt1p structurally changed from low-molecular-weight (LMW) forms to high-molecular-weight (HMW) complexes after heat shock. Based on our results, Ypt1p exhibited dual functions both as a GTPase and a molecular chaperone, and furthermore, heat shock induced a functional switch from that of a GTPase to a molecular chaperone driven by the structural change from LMW to HMW forms. Subsequently, we found, by using a galactose-inducible expression system, that conditional overexpression of YPT1 in yeast cells enhanced the thermotolerance of cells by increasing the survival rate at 55°C by ~60%, compared with the control cells expressing YPT1 in the wild-type level. Altogether, our results suggest that Ypt1p is involved in the cellular protection process under heat stress conditions. Also, these findings provide new insight into the in vivo roles of small GTP-binding proteins and have an impact on research and the investigation of human diseases. [ABSTRACT FROM AUTHOR]

Background We evaluated mortality among 5,964 former U.S. commercial cockpit crew (pilots and flight engineers). The outcomes of a priori interest were non-chronic lymphocytic leukemia, central nervous system (CNS) cancer (including brain), and malignant melanoma. Methods Vital status was ascertained through 2008. Life table and Cox regression analyses were conducted. Cumulative exposure to cosmic radiation was estimated from work history data. Results Compared to the U.S. general population, mortality from all causes, all cancer, and cardiovascular diseases was decreased, but mortality from aircraft accidents was highly elevated. Mortality was elevated for malignant melanoma but not for non-chronic lymphocytic leukemia. CNS cancer mortality increased with an increase in cumulative radiation dose. Conclusions Cockpit crew had a low all-cause, all-cancer, and cardiovascular disease mortality but elevated aircraft accident mortality. Further studies are needed to clarify the risk of CNS and other radiation-associated cancers in relation to cosmic radiation and other workplace exposures. [ABSTRACT FROM AUTHOR]

Introduction Although several studies have explored craving for certain drugs, there is limited data describing the relationship between alcohol and nicotine craving from a multidimensional perspective among individuals with comorbid nicotine dependence ( ND) and alcohol dependence ( AD). Methods We compared a group of male patients diagnosed with ND and AD ( n = 160) to a group of male patients diagnosed with ND only ( n = 235). Smoking- and drinking-related clinical features were measured, including craving levels and the Nicotine Dependence Syndrome Scale ( NDSS), which is a multidimensional questionnaire measuring ND. Subsequently, we studied factors that influenced smoking and alcohol craving in the ND and AD group. Results Regarding the NDSS, the sum, priority and tolerance scores were significantly higher in the ND and AD group compared with the ND only group ( P < 0.000, P < 0.000 and P = 0.001, respectively). In the comorbid group, regression analyses revealed that alcohol craving and Fagerstrom Test for Nicotine Dependence ( FTND) scores contributed to nicotine craving (beta coefficient = 0.37, P = 0.005 and beta coefficient = 0.35, P = 0.026, respectively) and these two factors explained 36% of the variance). Nicotine craving appeared to be the only factor that contributed to alcohol craving (beta coefficient = 0.35, P = 0.002), and nicotine craving explained 16% of the variance. Discussion This study may help clarify the clinical relationship between comorbid alcohol and nicotine dependence and help guide the development of effective treatment strategies for ND and AD patients. [ABSTRACT FROM AUTHOR]

As the system-on-chip (SoC) design becomes more complex, the test costs are increasing. One of the main obstacles of a test cost reduction is the limited number of test channels of the ATE while the number of pins in the design increases. To overcome this problem, a new test architecture using a channel sharing compliant with IEEE Standard 1149.1 and 1500 is proposed. It can significantly reduce the pin count for testing a SoC design. The test input data is transmitted using a test access mechanism composed of only input pins. A single test data output pin is used to measure the sink values. The experimental results show that the proposed architecture not only increases the number of sites to be tested simultaneously, but also reduces the test time. In addition, the yield loss owing to the proven contact problems can be reduced. Using the new architecture, it is possible to achieve a large test time and cost reduction for complex SoC designs with negligible design and test overheads. [ABSTRACT FROM AUTHOR]

The purpose of the present work is to study collinear unequal crack series in magnetoelectroelastic materials, which are of more practical significance than the widely studied collinear equal cracks. Fracture analysis is performed by the combined methods of distributed generalized dislocations, Green's function and singular integral equations (SIEs). The theoretical derivation is validated by the degeneration of SIEs in special cases. Parametric studies on the numerical results of mechanical strain energy release rate (MSERR) yield the following conclusions. (a) As two unequal cracks approach each other, interference occurs in crack tip fields, resulting in an obvious increase of MSERR. The ratio between the crack space and the length of the shorter crack is a main factor affecting the interference. (b) Negative or positive electric loading may shield or enhance crack growth, respectively. In the case of positive magnetic permeability, the effect of magnetic loading is analogous to that of electric loading; however, if magnetic permeability is negative, the result is completely opposite. (c) Positive values of magnetic permeability are found to be more reasonable than the negative values. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2011) 118, 855-863. Abstract Tissue plasminogen activator (tPA) is necessary for hippocampal long-term potentiation. Synaptically released zinc also contributes to long-term potentiation, especially in the hippocampal CA3 region. Using cortical cultures, we examined whether zinc increased the concentration and/or activity of tPA. Two hours after a 10-min exposure to 300 μM zinc, expression of tPA and its substrate, plasminogen, were significantly increased, as was the proteolytic activity of tPA. In contrast, increasing extracellular or intracellular calcium levels did not affect the expression or secretion of tPA. Changing zinc influx or chelating intracellular zinc also failed to alter tPA/plasminogen induction by zinc, indicating that zinc acts extracellularly. Zinc-mediated extracellular activation of matrix metalloproteinase (MMP) underlies the up-regulation of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase (Trk) signaling. Consistent with these findings, co-treatment with a neutralizing antibody against BDNF or specific inhibitors of MMPs or Trk largely reversed tPA/plasminogen induction by zinc. Treatment of cortical cultures with p-aminophenylmercuric acetate, an MMP activator, MMP-2, or BDNF alone induced tPA/plasminogen expression. BDNF mRNA and protein expression was also increased by zinc and mediated by MMPs. Thus, an extracellular zinc-dependent, MMP- and BDNF-mediated synaptic mechanism may regulate the levels and activity of tPA. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

The major objective of this study is to estimate Korean food shoppers' willingness to pay (WTP) for imported beef with traceability. We use an experimental elicitation method, the random nth price auction, to identify consumers' valuation for traceable imported beef. We also analyse the effect of different types of information on these valuations. Results indicate that consumers are generally willing to pay a 39 per cent premium for the traceable imported beef over similar beef without traceability. Results also suggest that in contrast to the insignificant effect of positive information, negative and two-sided information about traceability significantly reduces WTP. [ABSTRACT FROM AUTHOR]

Copolymers of N-isopropylacrylamide and octadecyl acrylate (PNO), of which the content of octadecyl acrylate (ODA) was 1.3% (PNO 1.5), 1.7% (PNO 2.0), and 3.0% (PNO 4.0), were prepared using a free radical reaction. Various assemblies were obtained depending on the concentration of PNOs and the contents of ODA. Hydrophobic interaction between ODA residues is likely to act as crosslinker. PNO 1.5 formed hydrogel at the concentration of 7%. With PNO 2.0, hydrogels were formed when the concentration was 5 and 7%. With PNO 4.0, the opaque gel was obtained when the concentration was 7%. Upon heating across the lower critical solution temperature, the hydrogels shrank but the opaque gel was broken down into a suspension. At 40°C, the release degrees of fluorescein isothiocyanate-dextran were much smaller than those of release at 23°C. The temperature-sensitive release is due to temperature-sensitive swelling ratio. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]

• Meloxicam is a substrate for the CYP2C9 and CYP3A4 enzymes. • We have previously reported that the frequency of the CYP2C9*1/*13 genotype in the Korean population is 1.1%. • The CYP2C9*1/*13 genotype is associated with decreased metabolism and increased pharmacodynamic effects of meloxicam. • This is the first report that evaluates the in vivo effects of the CYP2C9*13 allele on the pharmacokinetics and pharmacodynamics of CYP2C9 substrates with a sufficient sample size. To determine the effects of the CYP2C9*1/*13 genotype on the pharmacokinetics and pharmacodynamics of meloxicam in Korean subjects. Meloxicam (15 mg) was orally administered to 21 healthy Korean volunteers with either the CYP2C9*1/*1 or the CYP2C9*1/*13 genotype. Plasma meloxicam concentrations were analysed by HPLC-UV for 72 h after drug administration. The pharmacodynamic effects of meloxicam were determined by measuring TXB generated in blood. The AUC(0,∞) and C of meloxicam were 2.43- and 1.46-fold higher in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group, respectively. The oral clearance of meloxicam was significantly lower in the CYP2C9*1/*13 group (37.9% of wild type) than in the CYP2C9*1/*1 group. The t of meloxicam was 1.84-fold longer in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group. The rate of TXB production was significantly lower in the CYP2C9*1/*13 group than in the CYP2C9*1/*1 group. The CYP2C9*1/*13 genotype is associated with decreased metabolism and increased pharmacodynamic effects of meloxicam. [ABSTRACT FROM AUTHOR]

This paper is an empirical study to demonstrate the effect of the ethnocentric cultures of both Western interveners and national warring factions on civil war peace negotiations. By examining the peace negotiations in Cambodia and Angola, it demonstrates that actors' cultural values have significant effects on the formation of their goals, domestic resources, interveners' pressure and incentives, and contents of peace proposals. This paper also reveals that the strategic decisions of the national factions in the two cases varied according to the combined effects of the four factors just mentioned. [ABSTRACT FROM AUTHOR]

The article discusses a study on the prognostic role of tumor-infiltrating lymphocytes (TILs) in stage 2 colon cancers. The study was participated by patients who were diagnosed with pathologic stage 2 colon cancer after curative resection for colon carcinoma at the Samsung Medical Center at Sungkyunkwan University. The study concluded that FOXP3-positive and CD45RO-positive TILs have independent prognostic significance that can provide an independent predictor for prognosis and help refine the selection of patient subgroups with unfavorable prognosis.

Objective. Nuclear factor-κB (NF-κB) has been implicated as a therapeutic target for the treatment of rheumatoid arthritis (RA). The purpose of this study was to determine whether A20, a universal inhibitor of NF-κB, might have antiarthritic effects. Methods. An adenovirus containing A20 complementary DNA (AdA20) was used to deliver A20 to human rheumatoid fibroblast-like synoviocytes (FLS) in vitro as well as to mice with collagen-induced arthritis (CIA) in vivo via intraarticular injection into the ankle joints bilaterally. Results. In vitro experiments demonstrated that AdA20 suppressed NF-κB activation, chemokine production, and matrix metalloproteinase secretion induced by tumor necrosis factor α in FLS. Mice with CIA that were treated with AdA20 had a lower cumulative disease incidence and severity of arthritis, based on hind paw thickness, radiologic and histopathologic findings, and inflammatory cytokine levels, than did control virus-injected mice. The protective effects of AdA20 were mediated by the inhibition of the NF-κB signaling pathway. The severity of arthritis was also significantly decreased in the untreated front paws, indicating a beneficial systemic effect of local suppression of NF-κB. Surprisingly, mice treated with AdA20 after the onset of CIA had significantly decreased arthritis severity from the onset of clinical signs to the end of the study. Conclusion. These results suggest that using A20 to block the NF-κB pathway in rheumatoid joints reduces both the inflammatory response and the tissue destruction. The development of an immunoregulatory strategy based on A20 may therefore have therapeutic potential in the treatment of RA. [ABSTRACT FROM AUTHOR]

Autophagy is primarily considered a non-selective degradation process induced by starvation. Nutrient-independent basal autophagy, in contrast, imposes intracellular QC by selective disposal of aberrant protein aggregates and damaged organelles, a process critical for suppressing neurodegenerative diseases. The molecular mechanism that distinguishes these two fundamental autophagic responses, however, remains mysterious. Here, we identify the ubiquitin-binding deacetylase, histone deacetylase-6 (HDAC6), as a central component of basal autophagy that targets protein aggregates and damaged mitochondria. Surprisingly, HDAC6 is not required for autophagy activation; rather, it controls the fusion of autophagosomes to lysosomes. HDAC6 promotes autophagy by recruiting a cortactin-dependent, actin-remodelling machinery, which in turn assembles an F-actin network that stimulates autophagosome–lysosome fusion and substrate degradation. Indeed, HDAC6 deficiency leads to autophagosome maturation failure, protein aggregate build-up, and neurodegeneration. Remarkably, HDAC6 and F-actin assembly are completely dispensable for starvation-induced autophagy, uncovering the fundamental difference of these autophagic modes. Our study identifies HDAC6 and the actin cytoskeleton as critical components that define QC autophagy and uncovers a novel regulation of autophagy at the level of autophagosome–lysosome fusion. [ABSTRACT FROM AUTHOR]

The electron and proton transfer in phenol-imidazole-base systems (base = NH2- or OH-) were investigated by density-functional theory calculations. In particular, the role of bridge imidazole on the electron and proton transfer was discussed in comparison with the phenol-base systems (base = imidazole, H2O, NH3, OH-, and NH2-). In the gas phase phenol-imidazole-base system, the hydrogen bonding between the phenol and the imidazole is classified as short strong hydrogen bonding, whereas that between the imidazole and the base is a conventional hydrogen bonding. The n value in spn hybridization of the oxygen and carbon atoms of the phenolic CO sigma bond was found to be closely related to the CO bond length. From the potential energy surfaces without and with zero point energy correction, it can be concluded that the separated electron and proton transfer mechanism is suitable for the gas-phase phenol-imidazole-base triads, in which the low-barrier hydrogen bond is found and the delocalized phenolic proton can move freely in the single-well potential. For the gas-phase oxidized systems and all of the triads in water solvent, the homogeneous proton-coupled electron transfer mechanism prevails. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010 [ABSTRACT FROM AUTHOR]

The substituent effect of electron-withdrawing groups on electron affinity and gas-phase basicity has been investigated for substituted propynl radicals and their corresponding anions. It is shown that when a hydrogen of the α-CH3 group in the propynyl system is substituted by an electron-withdrawing substituent, electron affinity increases, whereas gas-phase basicity decreases. These results can be explained in terms of the natural atomic charge of the terminal acetylene carbon of the systems. The calculated electron affinities are 3.28 eV (•C&dbond;C&bond;CH2F), 3.59 eV (•C&tbond;C&bond;CH2Cl) and 3.73 eV (•C&tbond;C&bond;CH2Br), and the gas-phase basicities of their anions are 359.5 kcal/mol (-:C&tbond;C&bond;CH2F), 354.8 kcal/mol (:C&tbond;C&bond;CH2Cl) and 351.3 kcal/mol (-:C&tbond;C&bond;CH2Br). It is concluded that the larger the magnitude of electron-withdrawing, the greater is the electron affinity of radical and the smaller is the gas-phase basicity of its anion. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009 [ABSTRACT FROM AUTHOR]

We investigated the neuroprotective effect and mechanisms of action of cilnidipine, a long-acting, second-generation 1,4-dihydropyridine inhibitor of L- and N-type calcium channels, in PC12 cells that were neuronally differentiated by treatment with nerve growth factor (nPC12 cells). To evaluate the effect of cilnidipine on viability, nPC12 cells were treated with several concentrations of this drug before performing viability assays. Free radical levels and intracellular signaling proteins were measured with the fluorescent probe, 2′,7′-dichlorodihydrofluorescein diacetate and western blotting, respectively. Cell viability was not affected by low concentrations of cilnidipine up to 150 μM, but it was slightly decreased at 200 μM cilnidipine. Following H2O2 exposure, the viability of nPC12 cells decreased significantly; however, treatment with cilnidipine increased the viability of H2O2-injured nPC12 cells in a concentration-dependent manner. Treatment with H2O2 resulted in a concentration-dependent increase in free radical levels in nPC12 cells, and cilnidipine treatment reduced free radical levels in H2O2-injured nPC12 cells in a dose-dependent manner. Cilnidipine treatment increased the expression of p85 aPI3K (phosphatidylinositol 3-kinase) phosphorylated Akt, phosphorylated glycogen synthase kinase-3 (pGSK-3β), and heat shock transcription factor (HSTF-1) which are proteins related to neuronal cell survival, and decreased levels of cytosolic cytochrome c, activated caspase 3, and cleaved poly (ADP-ribose) polymerase (PARP), which are associated with neuronal cell death, in H2O2-injured nPC12 cells. These results indicate that cilnidipine mediates its neuroprotective effects by reducing oxidative stress, enhancing survival signals (e.g., PI3K, phosphorylated Akt, pGSK-3β, and HSTF-1), and inhibiting death signals from cytochrome c release, caspase 3 activation, and PARP cleavage. [ABSTRACT FROM AUTHOR]

Many studies suggest that adenosine modulates cell responses in a wide array of tissues through potent and selective regulation of cytokine production. This study examined the effects of adenosine on interleukin (IL)-6 expression and its related signal pathways in mouse embryonic stem (ES) cells. In this study, the adenosine analogue 5′-N-ethylcarboxamide (NECA) increased IL-6 protein expression level. Mouse ES cells expressed the A1, A2A, A2B, and A3 adenosine receptors (ARs), whose expression levels were increased by NECA and NECA-induced increase of IL-6 mRNA expression or secretion level was inhibited by the non-specific AR inhibitor, caffeine. NECA increased Akt and protein kinase C (PKC) phosphorylation, intracellular Ca2+ and cyclic adenosine monophosphate (cAMP) levels, which were blocked by caffeine. On the other hand, NECA-induced IL-6 secretion was partially inhibited by Akt inhibitor, bisindolylmaleimide I (PKC inhibitor), SQ 22536 (adenylate cyclate inhibitor) and completely blocked by the 3 inhibitor combination treatment. In addition, NECA increased mitogen activated protein kinase' (MAPK) phosphorylation, which were partially inhibited by the Akt inhibitor, bisindolylmaleimide I, and SQ 22536 and completely blocked by the 3 inhibitor combination treatment. NECA-induced increases of IL-6 protein expression and secretion levels were inhibited by MAPK inhibition. NECA-induced increase of nuclear factor (NF)-κB phosphorylation was inhibited by MAPK inhibitors. NECA also increased cAMP response element-binding protein (CREB) phosphorylation, which was blocked by MAPK or NF-κB inhibitors. Indeed, NECA-induced increase of IL-6 protein expression and secretion was blocked by NF-κB inhibitors. In conclusion, NECA stimulated IL-6 expression via MAPK and NF-κB activation through Akt, Ca2+/PKC, and cAMP signaling pathways in mouse ES cells. J. Cell. Physiol. 219: 752–759, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In yeast and animals, tri- and dimethylation of histone H3 at lysine 4 (H3K4me3/2) are markers of transcriptionally active genes that have recently been shown to be primary ligands for the plant homeodomain (PHD) finger. However, PHD fingers able to bind to H3K4me3/2 have not been identified in plants. Here, we identify 83 canonical PHD fingers in the Arabidopsis proteome database that are supported by both SMART and Pfam prediction. Among these, we focus on PHD fingers in ING (inhibitor of growth) homologues (AtING) and Alfin1-like (AL) proteins, which are highly similar to those in human ING2 and bromodomain PHD finger transcription factor (BPTF), based on predicted tertiary structures. ING proteins are found in yeast, animals and plants, whereas AL proteins exist only in plants. In vitro binding experiments indicated that PHD fingers in AtING and AL proteins in Arabidopsis can bind to H3K4me3, and, to a lesser extent, to H3K4me2. In addition, mutational analysis confirmed that a predicted aromatic cage and a specific conserved acidic residue are both crucial for binding to H3K4me3/2. Finally, we demonstrate that AtING and AL proteins are nuclear proteins that are expressed in various tissues of the Arabidopsis plant. Thus, we propose that ING and AL proteins are nuclear proteins that are involved in chromatin regulation by binding to H3K4me3/2, the active histone markers, in plants. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the metabolic significance of bisphenol A (BPA)-induced oxidative stress in rat urine measured by liquid chromatography and mass spectrometry. It investigates the profiling of 14 nucleosides in rat urine to determine (BPA)-induced oxidative stress. It states that nucleosides are formed by DNA repair as a result of oxidative DNA damage and post-transcriptionally modified transfer RNA (tRNA) in cells. Results found that quantitative alterations of dosage showed the metabolic trajectories responsible for physiological actions.

Glioblastoma (GBM) is a refractory disease that has a highly infiltrative characteristic. Over the past decade, GBM perivascular niche (PVN) has been described as a route of dissemination. Here, we investigated that trailed membrane structures, namely retraction fibers (RFs), are formed by perivascular extracellular matrix (ECM) proteins. By using the anatomical GBM database, we validated that the ECM-related genes were highly expressed in the cells within the PVN where fibronectin (FN) induced RF formation. By disrupting candidates of FN-binding integrins, integrin a5ß1 was identified as the main regulator of RF formation. De novo RFs were produced at the trailing edge, and focal adhesions were actively localized in RFs, indicating that adhesive force makes RFs remain at the bottom surface. Furthermore, we observed that GBM cells more frequently migrated along the residual RFs formed by preceding cells in microfluidic channels in comparison to those in the channels without RFs, suggesting that the infiltrative characteristics GBM could be attributed to RFs formed by the preceding cells in concert with chemoattractant cues. Altogether, we demonstrated that shedding membrane structures of GBM cells are maintained by FN-integrin α5β1 interaction and promoted their motility. [ABSTRACT FROM AUTHOR]

The dock plant ( Rumex spp.) is one of the most problematic pasture weeds worldwide. Allantus luctifer was selected as a potential biological control agent for Rumex spp. Continuous rearing of A. luctifer was carried out from 2005 to 2006, and its general biology is presented in this report. The preliminary host specificity test showed a promising result for using A. luctifer to control Rumex spp. [ABSTRACT FROM AUTHOR]

Background and Aim: The resection of synchronous or metachronous pulmonary and liver metastasis is an aggressive treatment option for patients with stage IV colorectal cancer and has been shown to yield acceptable long-term survival. We reviewed our experience with colorectal cancer patients with both liver and lung resections to determine the efficacy of surgical resections. Methods: We performed a single institution, retrospective analysis of all patients who underwent surgical hepatic and pulmonary resection for metastatic colorectal cancer between 1995 and 2004. Results: A total of 32 patients underwent resection of both hepatic and pulmonary metastases secondary to colorectal cancer. The 5-year overall survival from initial operation was 60.8%. The disease-free interval was 44.3 months (95% confidence interval: 24.7 and 63.8, respectively). Neither the number of pulmonary lesions nor the time interval between the primary surgery and the metastasectomy had a significant impact on survival ( P = 0.134). Conclusion: An aggressive surgical treatment of selected colorectal cancer patients with lung and liver metastases resulted in prolonged survival. The 5-year survival rate of 60.8% with no perioperative mortality was observed in our study. [ABSTRACT FROM AUTHOR]

Background and Aim: A high prevalence of intrahepatic stones in some areas of East Asia has been believed to be related with Clonorchis sinensis infection. The authors conducted a hospital-based case–control study to evaluate the role of Clonorchis sinensis infection as a risk factor for the development of gallstones in Korea. Methods: The cases of 138 patients with gallstones (intrahepatic 44, gallbladder 67, and extrahepatic 27) and matched controls underwent microscopy for C. sinensis, serological tests for C. sinensis using enzyme-linked immunosorbent assay, radiological examinations, and interviews concerning the history of eating raw freshwater fish. We assessed a relationship of three types of gallstones and variables regarding C. sinensis by using univariate and multivariate statistical analyses. Results: Univariate statistical analyses showed that radiological evidence of C. sinensis and recent history of eating raw freshwater fish were related to an increased risk of intrahepatic stones ( P = 0.0002 and 0.0039, respectively). According to multivariate statistical analyses, radiological evidence of C. sinensis was the only risk factor for intrahepatic stones (odds ratio = 7.835; 95% confidence interval = 1.671–36.724). Any evidence regarding C. sinensis was not related to an increased risk of either gallbladder or extrahepatic stones. Conclusion: Radiological evidence of C. sinensis was significantly associated with intrahepatic stones. [ABSTRACT FROM AUTHOR]

Anastomosis leakage is a major complication of rectal surgery. The aim of this study was to identify risk factors for anastomotic leakage after low anterior resection (LAR) in rectal cancer patients and study its impact on long-term prognosis and disease-free survival and overall survival in rectal cancer patients. Consecutive patients who underwent rectal resection with primary anastomosis below the pelvic peritoneal reflexion for rectal cancer between October 1996 to February 2006 were included. Anastomosis leakage after LAR occurred in 51 patients (4.0%). The median time to leakage was 4 days (range = 2–30 days). In univariate analysis, gender, level of anastomosis less than 4 cm, preoperative concomitant chemoradiation (CCRT), and length of operation greater than 120 min were significantly associated with anastomosis leakage. In a multivariate analysis, gender ( p = 0.041; relative risk = 2.007; 95% CI = 1.030–3.912) and preoperative CCRT ( p = 0.003; relative risk = 2.861; 95% CI = 1.417–5.778) were identified as independent prognostic factors. The overall survival of the nonleakage group and the leakage group was 80.2% and 64.9%, respectively ( p = 0.170). The 5-year disease-free survival rates were not significantly different between the nonleakage and leakage groups (78.1% vs. 65.9%, p = 0.166). The incidence of anastomotic leakage after low anterior resection is relatively low. Male gender and preoperative CCRT were associated with increased risk for anastomotic leakage after rectal cancer surgery. No effect of anastomosis leakage on local recurrence was found in this series. [ABSTRACT FROM AUTHOR]

Background: This study investigated the bone growth pattern in surgically created coronal defects with various depths around implants in dogs. Methods: Four mongrel dogs were used. All mandibular premolars were extracted under general anesthesia and left to heal for 2 months. After ostectomy, bony defects were prepared in test sites, using a stepped drill with a diameter of 6.3 mm and two depths: 2.5 mm (test sites 1 [T1]) and 5.0 mm (test sites 2 [T2]). In the control sites, the implants were placed after ostectomy without any coronal defects. T1, T2, and control sites were prepared in the right and left sides of the mandible. Six implants, 3.3 mm in diameter and 10 mm in length, were placed in each dog; the implants were submerged completely. Two dogs were sacrificed 8 weeks after surgery, and the other two dogs were sacrificed 12 weeks after surgery. The stability of all implants was measured with a resonance frequency analyzer after placement and after sacrifice. All sites were block-dissected for ground sectioning and histologic examination. Results: After 12 weeks of healing, only T2 were not filled fully with bone. At week 8, the mean bone-to-implant contact (BIC) was 47.7% for control, 43.6% for T1, and 22.2% for T2. At week 12, the control BIC was 56.7% and the 2.5-mm defect had a greater BIC (58.8%). However, in the 5 mm defect, the EIC was 35.1%. At insertion, stability was reduced at sites with a greater defect depth. Similar stability was noted in all specimens after 8 and 12 weeks of healing. Conclusion: Bone healing between an implant and marginal bone was compromised at sites with a deeper defect when the width of the bone defect was 1.5 mm. [ABSTRACT FROM AUTHOR]

Single crystals with the composition of 0.71Pb(Mg1/3Nb2/3)O3–0.29PbTiO3 (PMNT29) were grown using the solid-state crystal growth (SSCG) method. Compared with the conventional Bridgman grown crystals, the SSCG PMNT29 crystals were found to possess comparable piezoelectric, dielectric, and electromechanical properties ( d33∼1500 pC/N, ℇT33/ ℇ0∼5400 and k33∼90%), with the same Curie temperature ( TC) and ferroelectric phase transformation temperature ( T R– T). The full set of elastic, piezoelectric, and dielectric material constants were determined by the resonance method for the SSCG grown PMNT29 crystals according to IEEE standards and compared with Bridgman grown crystals. The dielectric temperature behavior and the strain field characteristics were investigated, demonstrating excellent performance over the temperature range from room temperature to 95°C. Strain behavior at high electric fields was found to be different from Bridgman growth crystals and believed to be attributed to different domain structures. [ABSTRACT FROM AUTHOR]

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DLPCBs) were determined in 122 coastal sediments from heavily industrialized areas in Korea. Toxic equivalent (TEQ) concentrations of PCDD and PCDF (PCDD/F) and DLPCB ranged from 0.44 to 38.5 pg/g dry weight and from 0.01 to 38.4 pg/ g dry weight, respectively. Overall PCDD/F and DLPCB concentrations were elevated in estuarine and inner bay locations close to industrial complexes, indicating that these contaminants derived from local discharges. Concentrations of PCDD/F measured in the present study were comparable to those in industrialized areas of other countries. Nonparametric multidimensional scaling ordination and congener-specific characterization showed that combustion processes occurring in industrial complexes, including the steel industry, are the major source of PCDD/Fs in Korean coastal waters. There were no significant correlations among PCDD/Fs, DLPCBs, and total organic carbon; however, there was moderate correlation between PCDD/Fs and DLPCBs in some coastal bays, suggesting that these chemicals have similar sources and movements in these locations. [ABSTRACT FROM AUTHOR]

Auranofin (AF) is a sulphur-containing gold compound. Because of its anti-inflammatory and immunosuppressive activities, AF has been widely used for the therapeutic treatment of rheumatoid arthritis. However, little is known about its mechanism of action. To elucidate the molecular mechanism underlying the anti-inflammatory effect of AF, we studied the effects of AF on cellular responses to interleukin-6 (IL-6). In HepG2 human hepatoma cells, AF markedly inhibited IL-6-induced phosphorylation of janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) and STAT3 translocation into the nucleus. Consistent with this, AF diminished IL-6-induced production of the acute-phase proteins, haptoglobin, fibrinogen, C3 complement and α1-acid glycoprotein, and gene expression of vascular endothelial growth factor, all of whose transcriptional activities are regulated by STAT3. The inhibitory activity of AF on STAT3 phosphorylation was also demonstrated in primary cells, i.e. fibroblast-like synoviocytes from rheumatoid arthritis patients, human umbilical vein endothelial cells and rat astrocytes. Auranofin-mediated inhibition of STAT3 phosphorylation was recovered by pretreatment with antioxidants containing thiol groups. These findings suggest that the anti-inflammatory action of AF is associated with a blockade of JAK1/STAT3 signalling. Thiol-group-reactive proteins may be involved in AF-induced suppression of JAK1/STAT3 phosphorylation. [ABSTRACT FROM AUTHOR]

Pb(Mg1/3Nb2/3)O3–PbZrO3–PbTiO3 (PMN–PZT) ferroelectric single crystals near morphotropic phase boundary compositions were fabricated by solid-state crystal growth. The Curie temperatures ( TC) of the grown PMN–PZT crystals were found to be on the order of 210°C, with ferroelectric phase transition temperatures ( T R– T) in the range of 96°–165°C. The electromechanical coupling factors k33 and k32 were found to be >90% and >−87%, respectively. The coercive field EC for all the compositions was on the order of 5 kV/cm, double the value of pure Pb(Mg1/3Nb2/3)O3–PbTiO3 (PMNT) crystals. The temperature dependence of the piezoelectric and electromechanical properties and dc bias effect on the dielectric behavior were investigated. The temperature usage range under dc bias was found to be improved when compared with pure PMNT crystals with similar piezoelectric properties. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles containing hinokitiol (HKL) were prepared by a melt-emulsification method. Stearic acid was used as a lipid for the matrix material of the nanoparticles. According to results from transmission electron microscopy (TEM) and dynamic light scattering (DLS), most of the nanoparticles were less than 100 nm. When nanoparticles containing HKL were scanned on a differential scanning calorimeter, no endothermic peak of HKL was observed. This means that HKL in the lipid matrix of the nanoparticles is in a dissolved state. In an 18-h permeation study using hairless mouse skin mounted on a diffusion cell, the amount of HKL encapsulated in the nanoparticles transported to the receptor cell was five to ten times more than for HKL dissolved either ethanol or propylene glycol. Therefore, stearic acid nanoparticles strongly enhanced permeation of the skin by HKL. [ABSTRACT FROM AUTHOR]

Because palpating colonic tumors during laparoscopy is impossible, the precise location of a tumor must be identified before operation. The aim of this study was to evaluate the accuracy of various diagnostic methods that are used to localize colorectal tumors and to propose an adequate localization protocol for laparoscopic colorectal surgery. A total of 310 patients underwent laparoscopy-assisted colectomy between April 2000 and March 2006. We investigated if the locations of the tumors that were estimated preoperatively were consistent with the actual locations according to the operation. All the tumors were correctly localized and resected. Altogether, 203 patients had complete endoscopic reports available. Colonoscopy was inaccurate for tumor localization in 23 cases (11.3%). In total, 104 patients (33.5%) underwent barium enema; five tumors (4.8%) were not visualized, and three tumors were incorrectly localized. Another group of 94 patients (30.3%) underwent computed tomography (CT) colonography, which identified 91 of 94 lesions (96.8%). Finally, 96 patients (31.0%) underwent endoscopic tattooing; 2 patients (2.1%) did not have tattoos visualized laparoscopically and required intraoperative colonoscopy to localize their lesions during resection. Dye spillage was found in six patients intraoperatively, but only one patient experienced clinical symptoms. Intraoperative colonoscopy was performed in four patients; two of the four were followed by endoscopic tattooing, and the other two underwent intraoperative colonoscopy for localization. All lesions were correctly localized by intraoperative colonoscopy. The accuracy of tumor localization was as follows: colonoscopy (180/203, 88.7%), barium enema (97/104, 93.3%), CT colonography (89/94, 94.7%), endoscopic tattooing (94/96, 97.9%), and intraoperative colonoscopy (4/4, 100%). With a combination of methods, localization of tumors for laparoscopic surgery did not seem very different from that during open surgery. Preoperative endoscopic tattooing is a safe, highly effective method for localization. In the case of tattoo failure, intraoperative colonoscopy can be used for accurate localization. [ABSTRACT FROM AUTHOR]