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Crosslinked helix dimers (CHDs) are synthetic tertiary helical structure motifs designed to modulate interactions of proteins with binding partners. Helix dimers serve as mimics of coiled coils, which are known to be implicated in a multitude of protein complexes. Coiled coils are typically stable in long peptides (21-28 residues), because sufficient intra- and interstrand contacts are not available in short peptides to coax strand assembly. To engineer conformationally stable CHDs in short sequences, we introduced a covalent linkage in place of an interhelical salt bridge and sculpted the helical interface with optimal hydrophobic packing. CHDs have shown efficacy for the disruption of targeted protein-protein interactions in biochemical, cellular, and animal models. This article describes our optimized approach to design and synthesize parallel and antiparallel helical tertiary structure mimics. Synthesis of CHDs involves conjugation of individual peptide segments, purification of the mono-conjugated strand, and alkylation of the two independent strands to yield crosslinked dimers. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Protocol for bis-triazole CHDs Basic Protocol 2: Protocol for dibenzyl ether CHDs.

Lung carcinoma is the main reason for cancer-associated deaths in the world. In a previous study, FCH domain only 1 (FCHo1) which is managed by protein kinase B (AKT), was shown to be activated in lung cancer. FCHo1 knockdown has previously been shown to cause cell death in lung cancer. However, the specific roles of FCHo1 in lung carcinoma remain elusive. Herein, we propose that FCHo1’s intracellular mechanism targets the G1 to S phase transition, following the M phase. We demonstrated that F-BAR and mu homology domains exist separately in human lung tissues and that one truncated form is not detected in patients with lung cancer. Furthermore, quantitative global proteome analysis of FCHo1 indicated that the inhibition of G1/S phase transition and FCHo1 RNAi led to the death of cells in the G1/S phase. Noninvasive viral aerosol-mediated delivery of FCHo1 shRNA suppressed cancer progression in mice with non-small-cell lung cancer (NSCLC), suggesting that the delivery of FCHo1 shRNA could be a meaningful therapeutic strategy in lung cancer. Additional studies are needed to make clear the detailed mechanism of action of FCHo1.

Satellite retrieval-based precipitation data with high spatial and temporal resolutions give an opportunity for precipitation research in regions with coarse networks of precipitation measuring instruments. This study evaluates the Integrated Multi-satellitE Retrievals for Global Precipitation Measurement (IMERG) data in Bangladesh and surrounding regions and then examines the diurnal variation of precipitation in these regions using the cyclostationary empirical orthogonal function (CSEOF) analysis method. The IMERG data capture the overall patterns of the diurnal variation of precipitation well, except for the overestimation of the degree of diurnal variability in the pre-monsoon season. The spatial distribution of precipitation is also captured well, except for the drastic horizontal change in precipitation within the northeastern region of Bangladesh. These encourage the use of the IMERG data for studying precipitation characteristics in Bangladesh and surrounding regions. Through the CSEOF analysis, the pre-monsoonal precipitation is characterized by the enhanced precipitation in the northern region of Bangladesh and the Meghalaya Plateau region in the late night to early morning. The monsoonal precipitation consists of two contrasting CSEOF modes. One shows enhanced precipitation in the northern region of the Bay of Bengal during 0600–1500 LST, related to the strong westerly moisture transport over the Bay of Bengal. The other shows enhanced precipitation in the southern slopes of the Meghalaya Plateau and Himalayan Foothills during 0000–0600 LST, associated with the strong southwesterly moisture transport toward these slopes that is neither blocked nor deflected by the Arakan Mountains.

In this study, nano-pores in cellulose acetate matrix were generated by utilizing glycerin with water pressure without metal salts as additive. When cellulose acetate polymer membrane fabricated with glycerin as an additive was exposed to water pressure as external physical force, nano-pore generation depends on the pressure-strength exerted on the membrane. On the principle of the nano-pore generation, the chains became weakened in the portion of the cellulose acetate, in which glycerin was surrounded by abundant water molecules, resulting in plasticization capable of easily generating nano-pores with water pressure. We found that pore size and numbers of nano-pore could be easily controlled by adjusting the water pressure. Thus, we succeeded in preparing the porous cellulose acetate with high porosity of 78.3%.Generated pores in cellulose acetate polymers were confirmed by scanning electron microscopy (SEM) images and porosimeter. The coordinate interactions between cellulose acetate (CA) polymers and glycerin were investigated by FT-IR and TGA analysis.

Bacterial DnaK is an ATP-dependent molecular chaperone important for maintaining cellular proteostasis in concert with cofactor proteins. The cofactor DnaJ delivers non-native client proteins to DnaK and activates its ATPase activity, which is required for protein folding. In the bacterial pathogen

The purpose of this study was to verify whether the type of national disaster management organization affects resilience capability and organizational effectiveness. In the present study, we analyzed a previous study conducted by Hollnagel on the inter-relationship between resilience capability and organizational effectiveness. Our results confirmed that public officers who are in charge of disaster management need to increase their resilience capability in order to improve organizational effectiveness. However, we cannot conclude that disaster management efficiency is improved only by increasing public officers' resilience capability. This study suggests that a dedicated organization for disaster management should be created to ensure effective handling of disasters. The influence of the type of organization should be considered, based on the results of this study.

Protein-protein interactions featuring intricate binding epitopes remain challenging targets for synthetic inhibitors. Interactions of NEMO, a scaffolding protein central to NF-κB signaling, exemplify this challenge. Various regulators are known to interact with different coiled coil regions of NEMO, but the topological complexity of this protein has limited inhibitor design. We undertook a comprehensive effort to block the interaction between vFLIP, a Kaposi’s sarcoma herpesviral oncoprotein, and NEMO using small molecule screening and rational design. Our efforts reveal that a tertiary protein structure mimic of NEMO is necessary for potent inhibition. The rationally designed mimic engages vFLIP directly causing complex disruption, protein degradation and suppression of NF-κB signaling in primary effusion lymphoma (PEL). NEMO mimic treatment induces cell death and delays tumor growth in a PEL xenograft model. Our studies with this inhibitor reveal the critical nexus of signaling complex stability in the regulation of NF-κB by a viral oncoprotein., NF-κB signalling involves the scaffold protein NEMO, which can be bound by the oncoprotein vFLIP to promote cell survival and oncogenic transformation. Here the authors rationally engineer a tertiary protein mimic of NEMO to disrupt the vFLIP-NEMO interaction to induce cell death.

In this study, numerical models of an active thermal management system (TMS) using a two-phase refrigerant and a passive TMS using phase change material (PCM) for lithium ion batteries in electric vehicles (EVs) and hybrid electric vehicles (HEVs) are developed. The models are validated by comparing the predictions with the measured data. The effects of the refrigerant temperature and mass flow rate on the cooling performance of the refrigerant-cooled active TMS are analyzed. Moreover, the cooling performance characteristics of the refrigerant-cooled active and PCM-based passive TMSs are compared under various single discharge and cyclic operating conditions. The passive and active TMSs show excellent performances under mild and stressful operating conditions where discharge occurs. However, in the cyclic operation where charge and discharge are merged, the refrigerant-cooled active TMS shows better cooling performance than the PCM-based passive TMS.

The objective of this study is to evaluate the thermal performance improvement of an ultrathin, flat plate pulsating heat pipe (PHP) against a graphite sheet for use in mobile electronic devices. Initially, the thermal performances of five PHP models with various channel designs are quantified, and an optimum PHP is selected to achieve the best performance. In the optimum PHP, the thermal performance is analyzed as a function of the heat input and condenser temperature. Finally, the finished product of the flat plate PHP is fabricated using a diffusion bonding technique. The thermal performance of the finished flat plate PHP is then compared with that of the graphite sheet based on conducted tests at the inclination angles of 90°, 0°, and −90°. The thermal resistances of the finished flat plate PHP at the inclination angles of 90° and 0° are 63% and 56%, respectively, lower than those of the graphite sheet, whereas the resistance at the inclination angle of −90° is almost the same as that of the graphite sheet.

Helical secondary and tertiary motifs are commonly observed as binding epitopes in natural and engineered protein scaffolds. While several strategies have been described to constrain α-helices or reproduce their binding attributes in synthetic mimics, general strategies to mimic tertiary helical motifs remain in their infancy. We recently described a synthetic strategy to develop helical dimers ( J. Am. Chem. Soc. 2015, 137, 11618-11621). We found that replacement of an interhelical salt bridge with a covalent bond can stabilize antiparallel motifs in short sequences. Here we show that the approach can be generalized to obtain antiparallel and parallel dimers as well as trimer motifs. Helical stabilization requires judiciously designed cross-linkers as well as optimal interhelical hydrophobic packing. We anticipate that these mimics would afford new classes of modulators of biological function.

Aberrant Ras signaling is linked to a wide spectrum of hyperproliferative diseases, and components of the signaling pathway, including Ras, have been the subject of intense and ongoing drug discovery efforts. The cellular activity of Ras is modulated by its association with the guanine nucleotide exchange factor Son of sevenless (Sos), and the high-resolution crystal structure of the Ras-Sos complex provides a basis for the rational design of orthosteric Ras ligands. We constructed a synthetic Sos protein mimic that engages the wild-type and oncogenic forms of nucleotide-bound Ras and modulates downstream kinase signaling. The Sos mimic was designed to capture the conformation of the Sos helix-loop-helix motif that makes critical contacts with Ras in its switch region. Chemoproteomic studies illustrate that the proteomimetic engages Ras and other cellular GTPases. The synthetic proteomimetic resists proteolytic degradation and enters cells through macropinocytosis. As such, it is selectively toxic to cancer cells with up-regulated macropinocytosis, including those that feature oncogenic Ras mutations.

In this study, a cellulose acetate (CA) membrane with pores generated by a water pressure treatment was investigated for its ability to serve as a pretreatment filter device for the detection of 2-n-octyl-4-isothiazolin-3-one (OIT). Pores were generated by applying a water pressure of 8 bar to a membrane manufactured using a CA-based polymer solution. The CA used for the manufacturing was an environment-friendly, low-cost and highly energy-efficient material. Furthermore, since the fabricated porous CA polymeric film possessed many hydrophilic functional groups, it could strongly bind hydrophilic substances while avoiding interaction with hydrophobic substances. OIT, which comprises a hydrophobic bond that forms weak bonds over time, can break down more easily than hydrophilic impurities. The different extents of interaction occurring between either the toxic fungicide OIT or the hydrophilic impurities and the CA film were determined by Fourier-transform infrared (FT-IR) spectroscopy. The physicochemical changes in the resulting membrane, which occurred when the pores were generated, were investigated through scanning electron microscopy (SEM) and thermogravimetric analysis (TGA).

Lithium-ion (Li-ion) batteries have been considered as the most promising energy storage devices for electric vehicles. An efficient battery thermal management system (BTMS) should be developed for the performance and life cycles of the batteries. The objective of this study is to analyze the thermal performance of a novel liquid cooling system combined with heat pipes for Li-ion batteries under various operating conditions and design parameters. A transient thermo-fluid simulation is developed to analyze the cooling performance characteristics of three BTMSs: (1) liquid cooling (LC), (2) liquid cooling with A-type heat pipes (LCA), and (3) liquid cooling with B-type heat pipes (LCB). The LCB shows a much higher performance than the LC, owing to the increased heat transfer area. The effects of the discharge rate, liquid mass flow rate, liquid temperature, and ambient temperature on the cooling performances of the BTMSs are investigated. The figure of merit is analyzed for various BTMSs with respect to the discharge rate and liquid mass flow rate. Additionally, the effective thermal conductivity of the heat pipe and thermal conductivity of the battery cell are analyzed to provide design guides. Finally, the cooling performance of the BTMS with the optimized design parameters is compared to that under basic conditions. The maximum temperatures of the battery module in the LCB decrease by 6.1 °C and 9.4 °C under the basic and optimized conditions relative to those in the LC, respectively.

PEMFC needs to be maintained at an appropriate temperature and humidity in a rapidly changing environment for automobile applications. In this study, a pseudo-multi-dimensional dynamic model for predicting the heat and mass transfer performance of a plate-and-frame membrane humidifier for PEMFC vehicles is developed. Based on the developed model, the variations in the temperature and relative humidity at the dry air outlet are investigated according to the air flow acceleration. Moreover, the dynamic response is analyzed as a function of the amplitude and period of the sinusoidal air flow rate at actual operating conditions. The effects of heat transfer on the dynamic response are more dominant than those of mass transfer. The settling time of the temperature and relative humidity at the dry air outlet decrease with the increase in air flow acceleration. In addition, the variations in the temperature and relative humidity at the dry air outlet increase with the increases in the amplitude and period of the sinusoidal air flow rate.

Present paper investigates the potential configuration of post-accident fuel debris for a severe accident in a nuclear power plant. The physical and chemical behaviors of molten core material are investigated by experimental efforts. A series of melting and solidification experiments utilizing a cold crucible technique was performed using corium of 4.5–15 kg at various compositions. Considering that U/Zr atom ratio and Zr oxidation index could vary substantially during the accident progression, corium melts at compositions with U/Zr in the range of 0.94–1.14 and Zr oxidation index in the range of 36.3–100% were investigated. It was found that the solidified corium separated into a metal rich and an oxide rich layer in cases of partially oxidized corium. Depending on the compositions, metal rich layer was placed either on top or at the bottom of the oxide rich layer. Inductively Coupled Plasma-Atomic Emission Spectroscopy was used to estimate the chemical compositions of the layers and X-Ray Diffraction was used to find the crystal structure of the layers. In the second series of experiments, a molten corium of 13 kg in the form of liquid jet is poured into a pool of water. Melt water interaction resulted in fragmented and quenched particles with a range of size distributions. Scanning Electron Microscope and Electron Probe Micro-Analysis were used to analyze the physical and chemical behaviors of the particles. Partially oxidized corium melt resulted in a quenched particles with irregular shape. The composition of the particles varied among different particles and also within a particle. Fully oxidized melt resulted in quenched particles with homogenous composition among different particles and homogenous distribution of composition within a particle. The shape of these particles was spheroid in most of cases.

Corrosion inhibitors including calcium hydroxide have been used to prevent corrosion in the pipes for tap water supply. The corrosion index (i.e., Langelier Index) differs by area and water quality. The corrosion indices of the areas studied differed by more than 2.0. The ‘homogenized’ calcium hydroxide was added to the treated water at the K water treatment plant, in order to increase the value of the corrosion index and the concentration of calcium. As the result, the concentration of calcium was increased while the turbidity and pH changed little. The corrosion rate of the tap water with the ''homogenized'' calcium hydroxide could be slowed down pretty much. The results suggested that the technology of ''homogenization'' of calcium hydroxide can applied to tap water and desalinated water to prevent corrosion in water pipes even in corrosive pipes.

This study aims to investigate the quenching performance of hot stamping blanks by two-phase refrigerant and conventional single-phase cooling. A low-global-warming potential refrigerant, R1234yf, is used as the working fluid for the two-phase refrigerant cooling. The quenching performance of the water and R1234yf cooling methods is evaluated experimentally and via simulations using a three-dimensional transient thermo-fluid model. The R1234yf cooling method presents a higher cooling capacity and energy efficiency than the water cooling method owing to the effective evaporative heat transfer characteristics of the former. Under the same mass flow rate conditions, the blank hardness and its standard deviation achieved by the R1234yf cooling method are 7.3–31.5 HV higher and 13.1–54.3% lower than those by the water cooling method, respectively. Furthermore, the R1234yf cooling method decreases the hotspot area in the internal lower die and realizes a more uniform temperature distribution compared to water cooling. In addition, the daily production by the R1234yf cooling method is 9.5 − 15.3% higher than that by the water cooling method owing to the shorter approach time to the martensite finish temperature in the former. Accordingly, owing to its higher blank quality and productivity, the R1234yf cooling method has a superior quenching performance than water cooling during the hot stamping process.

We describe the use of thioester exchange equilibria to measure the propensities of amino acid residues to participate in helical secondary structure at room temperature in the absence of denaturants. Thermally or chemically induced unfolding has previously been employed to measure α-helix propensities among proteinogenic α-amino acid residues, and quantitative comparison with precedents indicates that the thioester exchange system is reliable for residues that lack side chain charge. This system allows the measurement of α-helix propensities for D-α-amino acid residues and propensities of residues with non-proteinogenic backbones, such as those derived from a β-amino acid, to participate in an α-helix-like secondary structure.

Background/Aim: Lung cancer shows the highest estimated deaths in both males and females in the Unites States. Importin 7 is overexpressed in lung adenocarcinoma tissues. In this study, we aimed to demonstrate the anticancer effect of importin 7 down-regulation, especially in lung cancer. Materials and Methods: Glycerol propoxylate triacrylate spermine (GPT-SPE) is a biocompatible carrier used for aerosol gene delivery. Repeated aerosol delivery of GPT-SPE/shImportin 7 complexes was performed to 10-week-old male K-rasLA1mice (a murine lung cancer model) twice a week for 4 weeks (8 times) in a nose-only exposure chamber. Results: Aerosol delivery of GPT-SPE/shImportin 7 inhibits lung cancer in K-rasLA1mice compared to control and scramble control groups. Moreover, importin 7-down-regulated stable cell-line demonstrates suppression of proliferation through Akt inhibition and apoptosis. Conclusion: Down-regulation of importin 7 significantly suppresses lung cancer in vitro and in vivo.

This study used an integrated approach to investigate the effects of Gymnema sylvestre (GS) extract as a functional dietary supplement with a high-fat diet. This approach examined insulin resistance, the dysfunction of adipose tissue, and liver steatosis. Male C57BL/6J mice were fed a normal chow or high-fat diet (HFD) for the acute and chronic study, in addition to GS in different doses (100, 250 and 500[Formula: see text]mg/kg body weight). Their body composition changes, serum lipid and glucose parameters, adipose and liver tissue histology, and gene expression were measured. It was found that GS significantly suppressed the increase of body weight, serum levels of lipid, insulin and leptin, and adipose tissue, and liver inflammation. GS also demonstrated hypoglycemic effects due to the amylase inhibition activity. Our results support the existence of a relationship between the HFD induced insulin resistance, adipose dysfunction and liver steatosis. In conclusion, GS works as a functional dietary supplement with preventative effects against metabolic disorder.

Some advanced reactors adapt the in-vessel corium retention concept by cooing the outside wall of the reactor vessel in severe accidents. If a reactor vessel failure happens in this case, the molte...

Coexisting attractors may arise from many different sources such as hidden basins of attraction or peculiarly organized bifurcation structures. By exploiting the regions of mismatched bifurcations between the system and its fixed points, this study investigates coexisting attractors in a six-dimensional extension of the Lorenz system. This six-dimensional extension takes into account additional physical ingredients, namely, rotation and density-affecting scalar, which are not considered in the original Lorenz system. These newly considered physical ingredients can influence the bifurcation structures and thus the system’s characteristics with regard to coexisting attractors. Once the potential regions of coexisting attractors are identified in the parameter spaces, the coexistence of periodic and point attractors and that of two different periodic orbits in addition to the well-known coexistence of chaos and stability are demonstrated through the solution trajectories and attractor basin boundaries.

Aside from kidney transplantation - a procedure which is exceedingly dependent on donor-match and availability leading to excessive costs - there are currently no permanent treatments available which reverse kidney injury and failure. However, kidney-specific targeted gene therapy has outstanding potential to treat kidney-related dysfunction. Herein we report a novel kidney-specific targeted gene delivery system developed through the conjugation of chitobionic acid (CBA) to a polysorbitol gene transporter (PSGT) synthesized from sorbitol diacrylate and low molecular weight polyethylenimine (PEI) carrying hepatocyte growth factor (HGF) gene to alleviate unilateral ureteral obstruction (UUO) in rats. CBA-PSGT performed exceptionally well for targeted delivery of HGF to kidney tissues compared to its non-targeted counterparts (P 0.001) after systemic tail-vein injection and significantly reduced the UUO symptoms, returning the UUO rats to a normal health status. The kidney-targeted CBA-PSGT-delivered HGF also strikingly reduced various pathologic and molecular markers in vivo such as the level of collagens (type I and II), blood urea nitrogen (BUN), creatinine, and the expressions of ICAM-1, TIMP-1 and α-SMA which play a critical role in obstructive kidney functions. Therefore, CBA-PSGT should be further investigated because of its potential to alleviate UUO and kidney-related diseases using high affinity kidney targeting.

// Seong-Ho Hong 1, 2 , Seung-Hee Chang 1 , Kyung-Cho Cho 3 , Sanghwa Kim 1, 4 , Sungjin Park 1 , Ah Young Lee 1 , Hu-Lin Jiang 5 , Hyeon-Jeong Kim 1 , Somin Lee 1, 4 , Kyeong-Nam Yu 1 , Hwi Won Seo 6 , Chanhee Chae 6 , Kwang Pyo Kim 3 , Jongsun Park 7 , Myung-Haing Cho 1, 4, 8, 9, 10 1 Laboratory of Toxicology, BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea 2 New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Korea 3 Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin 17104, Korea 4 Graduate Group of Tumor Biology, Seoul National University, Seoul 08826, Korea 5 Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China 6 Laboratory of Pathology, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea 7 Department of Pharmacology and Medical Science, Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 35015, Korea 8 Graduate School of Convergence Science and Technology, Seoul National University, Suwon 16229, Korea 9 Advanced Institute of Convergence Technology, Seoul National University, Suwon 16229, Korea 10 Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun 25354, Korea Correspondence to: Myung-Haing Cho, email: mchotox@snu.ac.kr Jongsun Park, email: insulin@cnu.ac.kr Keywords: lung cancer, gene therapy, endoplasmic reticulum-Golgi intermediate compartment protein 3 (ERGIC3), golgi apparatus, ER stress Received: February 01, 2016 Accepted: August 08, 2016 Published: August 29, 2016 ABSTRACT Trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus is elevated in cancer cells. Therefore, proteins of the ER-Golgi intermediate compartment (ERGIC) attract significant attention as targets for cancer treatment. Enhanced cancer cell growth and epithelial-mesenchymal transition by ERGICs correlates with poor-prognosis of lung cancer. This prompted us to assess whether knockdown of ERGIC3 may decrease lung cancer growth. To test the hypothesis, the effects of ERGIC3 short hairpin RNA (shERGIC3) on ER stress-induced cell death and lung tumorigenesis were investigated both in vitro and in vivo . Knockdown of ERGIC3 led to ER stress-induced autophagic cell death and suppression of proliferation in the A549 human lung cancer cell-line. Moreover, non-invasive aerosol-delivery of shERGIC3 using the biocompatible carrier glycerol propoxylate triacrylate and spermine (GPT-SPE) inhibited lung tumorigenesis in the K-ras LA1 murine model of lung cancer. Our data suggest that suppression of ERGIC3 could provide a framework for the development of effective lung cancer therapies.

Steam explosion experiments are performed at various modes of melt water interaction configuration using prototypic corium melt. The tests are performed to simulate both melt water interaction in a...

The lithium-ion battery has been considered as a power source of electric vehicles (EVs). An efficient battery thermal management system is essential for lithium-ion batteries with high cooling performance and long lifetime. The objective of this study is to investigate the performance improvement of a novel direct two-phase refrigerant cooling over a conventional liquid cooling for traction batteries of EVs. Based on full-scale experiments under actual vehicle conditions, the thermal performance of the two-phase refrigerant cooling is compared with that of the conventional liquid cooling with the same outer size. The two-phase refrigerant cooling satisfies the maximum cell temperature limit of 45 °C even under harsh environmental conditions. During aging, the two-phase refrigerant cooling provides 16.1% higher battery capacity and 15.0% lower internal resistance compared with the liquid cooling under harsh environmental conditions. Overall, the two-phase refrigerant cooling is considered a preferred alternative to the conventional liquid cooling owing to its reliable performance even with a simple and lightweight structure.

A thiol-thioester exchange system has been used to measure the propensities of diverse β-amino acid residues to participate in an α-helix-like conformation. These measurements depend on formation of a parallel coiled-coil tertiary structure when two peptide segments become linked by thioester formation. One peptide segment contains a “guest” site that accommodates diverse β residues and is distal to the coiled-coil interface. We find that helix propensity is influenced by side chain placement within the β residue [β(3) (side chain adjacent to nitrogen) slightly favored relative to β(2) (side chain adjacent to carbonyl)]. The previously recognized helix stabilization resulting from five-membered ring incorporation is quantified. These results are significant because so few quantitative thermodynamic measurements have been reported for α/β-peptide folding.

Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC50 values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 &mu, M and 44.7 &mu, M, while those of magnolol were 19.0 &mu, M and 47.3 &mu, M, respectively. Notably, the systemic exposure (AUC and Cmax) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration of intravenous honokiol or magnolol. The differential effects of the two phytochemicals on phenacetin and diclofenac in vivo pharmacokinetics could at least be partly attributed to their lower IC50 values for the inhibition of phenacetin metabolism than for diclofenac metabolism. In addition, the systemic exposure, CL, and Vss of honokiol and magnolol tended to be similar between the rat groups receiving phenacetin and diclofenac. These findings improve our understanding of CYP-mediated drug interactions with M. officinalis and its active constituents.

This study was carried out to elucidate the partial substitutability of SB latex with envi-ronmental-friendly coating binders for coated paper. Starch-based biobinder, ethylene vinyl acetate and acryl-based binder were evaluated for this purpose. Several combina-tions of above binders were applied to top layer coating, and properties of coating colors and printability were evaluated. When 20% and 30% of SB latex were substituted by acryl-based synthetic binder, eth-ylene vinyl acetate and biobinder, the brightness, whiteness and opacity of coated paper were similar to those obtained from SB latex. Ink set and stiffness of coated paper man-ufactured through 20% and 30% substitution of SB latex by biobinder and EVAc were im-proved, but dry- and wet-pick strength were decreased. The research works on the im-provement of dry- and we-pick strength, mechanical stability and rheological properties at high shear condition should be continued for the commercial application of biobinder, EVAc and acryl-based binder.Keywords: SB latex, biobinder, synthesized binder, top-coating, printability

In this study, we examined the mechanism underlying the effect of Saururus chinensis Baill (saururaceae) on hepatocellular carcinoma HepG2 cells. HepG2 cells and Chang cells were exposed to various concentrations of S. chinensis Baill extract (SC-E) for 24 h. SC-E affected more significantly HepG2 cells than Chang cells in terms of cell viability and ATP production. Therefore, current study examined detailed mechanism how SC-E affected HepG2 cell survival. We found that SC-E (75 and 150 μg/ml) induced apoptosis via oxidative stress. SC-E also caused CCAAT-enhancer-binding protein homologous protein (CHOP) activation by dissociating the binding immunoglobulin protein (BiP) from inositol-requiring 1α (IRE1α) in the endoplasmic reticulum (ER) and induced Bax, cytochrome c release to cytosol, caspase-3 activation, and poly ADP ribose polymerase (PARP) cleavage, resulting in HepG2 cell apoptosis. Furthermore, SC-E caused ER Ca(2+) leakage into the cytosol; ER dilation and mitochondrial membrane damage were observed in transmission electron microscopy (TEM). Taken together, our results demonstrated that SC-E induced cancer cell apoptosis specifically through ER stress.

This paper presents a velocity-synchronizing control for the multiple axes of an injection unit; based on MBS, a virtual design model has been developed for the multiple-axes servomechanism. Prior to the design of the controller, a linear plant model was derived via open- loop response simulations. To synchronize the motions of the multiple axes, a cross-type synchronizing controller was designed and combined with the PID control to accommodate any parameter mismatches among the multiple axes. From the tracking control simulations, a significant reduction of both velocity-tracking and position-tracking errors was achieved through the use of the proposed control scheme.

Steam explosions by the interaction of molten corium with water have been studied extensively because they may have the potential to impact the integrity of the containment. Since breakup and fragm...

Inorganic phosphate (Pi) plays crucial roles in several biological processes and signaling pathways. Pi uptake is regulated by sodium-dependent phosphate (Na/Pi) transporters (NPTs). Moreover, Pi is used as a food additive in food items such as sausages, crackers, dairy products, and beverages. However, the high serum concentration of phosphate (> 5.5 mg/dL) can cause adverse renal effects, cardiovascular effects including vascular or valvular calcification, and stimulate bone resorption. In addition, Pi can also alter vital cellular signaling, related to cell growth and cap-dependent protein translation. Moreover, intake of dietary Pi, whether high (1.0%) or low (0.1%), affects organs in developing mice, and is related to tumorigenesis in mice. The recommended dietary allowance (RDA) of Pi is the daily dietary intake required to maintain levels above the lower limit of the range of normal serum Pi concentration (2.7 mg/dL) for most individuals (97-98%). Thus, adequate intake of Pi (RDA; 700 mg/day) and maintenance of normal Pi concentration (2.7-4.5 mg/dL) are important for health and prevention of diseases caused by inadequate Pi intake.

Air freshener could be one of the multiple sources that release volatile organic compounds (VOCs) into the indoor environment. The use of these products may be associated with an increase in the measured level of terpene, such as xylene and other volatile air freshener components, including aldehydes, and esters. Air freshener is usually used indoors, and thus some compounds emitted from air freshener may have potentially harmful health impacts, including sensory irritation, respiratory symptoms, and dysfunction of the lungs. The constituents of air fresheners can react with ozone to produce secondary pollutants such as formaldehyde, secondary organic aerosol (SOA), oxidative product, and ultrafine particles. These pollutants then adversely affect human health, in many ways such as damage to the central nervous system, alteration of hormone levels, etc. In particular, the ultrafine particles may induce severe adverse effects on diverse organs, including the pulmonary and cardiovascular systems. Although the indoor use of air freshener is increasing, deleterious effects do not manifest for many years, making it difficult to identify air freshener-associated symptoms. In addition, risk assessment recognizes the association between air fresheners and adverse health effects, but the distinct causal relationship remains unclear. In this review, the emitted components of air freshener, including benzene, phthalate, and limonene, were described. Moreover, we focused on the health effects of these chemicals and secondary pollutants formed by the reaction with ozone. In conclusion, scientific guidelines on emission and exposure as well as risk characterization of air freshener need to be established.

A large amount of fructose intake along with smoking is associated with increased incidence of diseases linked to metabolic syndrome. More research is necessary to understand the complex mechanism that ultimately results in metabolic syndrome and the effect, if any, of high fructose dietary intake and smoking on individual health. In this study, we investigated changes in ER-Golgi network and disturbance to secretion of adipokines induced by cigarette smoking (CS) and excess fructose intake and their contribution to the disruption of metabolic homeostasis. We used high fructose-induced metabolic disorder mice model by feeding them with high fructose diet for 8 weeks. For CS exposure experiment, these mice were exposed to CS for 28 days according to OECD guideline 412. Our results clearly showed that the immune system was suppressed and ER stress was induced in mice with exposure to CS and fed with high fructose. Furthermore, their concentrations of adipokines including leptin and adiponectin were aberrant. Such alteration in secretion of adipokines could cause insulin resistance which may lead to the development of type 2 diabetes.

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common chronic liver disease worldwide. Sphingolipids are a family of lipids that play essential roles as critical regulators in metabolic disorders. Some sphingolipids are known key factors in metabolic dysfunction. However, the precise effect of dihydroceramide on NAFLD remains unknown. Here, we report how dihydroceramide in autophagosome accumulation activates fibrogenesis in human liver Chang cells treated with free fatty acids (FFA). According to LC/MS lipid profiling, FFA increased the levels of sphingolipids and triacylglycerol (TG). To demonstrate the potential role of dihydroceramide metabolism in autophagy, several sphingolipid synthesis inhibitors were used. Increased dihydroceramide led to impairment of autophagic flux, resulting in increased TG storage in lipid droplets (LD) and upregulated expression of fibrosis markers. Hepatic stellate cells (HSCs, LX-2 cells) were co-cultured with Chang cells to assess the potential fibrogenic response to dihydroceramide, Treatment with rapamycin recovered autophagic flux in Chang cells and fibrogenesis in the co-culture system. Our results identified a critical function of dihydroceramide metabolism in autophagy. It could play an important role in the progression of NAFLD associated with lipid over-accumulation. Therefore, preventing autophagic flux by regulating dihydroceramide could be a potential strategic approach for providing therapy for NAFLD.