Air Filtration and Radon Decay Product Mitigation

Air cleaning as a means of mitigating the risks arising from exposure to indoor radon progeny has been evaluated in a single-family house in the north eastem US. using an automated, semi-continuous activity-weighted size distribution measurement system. The measurements included radon concentration, condensation nuclei count, and activity-weighted size distribution of radon decay products. Measurements were made in the house with and without an operating air filtration system and with various particle sources common to normal indoor activities operating. Aerosols were generated by running water in a shower, candle burning, cigarette smoking, vacuuming, opening doors, and cooking. Using a room model, the changes in attachment rates, average attachment diameters, and deposition rates of the unattached fraction with and without the air cleaning system were calculated. In the presence of active aerosol sources, the air filtration unit typically reduced the concentration of particles within the hour following the end of particle generation. After candle burning, cigarette smoking, and vacuuming in the bedroom, the reductions of PAEC by air filtration are about 60% with the air filtration system operating in the bedroom. During cooking in the kitchen, the reductions of PAEC in the bedroom with the air filtration system were about 40%. However, for all cases the dose reductions were smaller than the particle and PAEC reductions. For those particles that were generated within the bedroom, there was a 20% to 50% reduction in dose. In the case of cooking where the door was open and particles infiltrated from the rest of the house, the dose reduction was only 5% on average and appears to be insignificant. Thus, the dose reductions were h e r than the reductions in activity concentration, but there were no cases where the estimated dose actually increased.     

EFFECT OF THE RATIO Th/U ON TL DATING ACCURACY

ＥＦＦＥＣＴＯＦＴＨＥＲＡＴＩＯＴｈ／ＵＯＮＴＬＤＡＴＩＮＧＡＣＣＵＲＡＣＹ￥Ｐ．Ｌ．Ｌｅｕｎｇ（梁宝鎏）；ＭｉｃｈａｅｌＪ．Ｓｔｏｋｅｓ（ＤｅｐａｒｔｍｅｎｔｏｆＰｈｙｓｉｃｓａｎｄＭａｔｅｒｉａｌｓＳｃｉｅｎｃｅ，ＣｉｔｙＰｏｌｙｔｅｃｈｎｉｃｏ...     

未知钍—铀比的误差分析

研究了在任意Th、U含量和Th-U比覆盖整个范围(即0≤Th/U≤∝)时总α计数率对年剂量的转换因子及其误差。结果表明,当不测定Th-U比而只测量总α计数率时,最终引起的年龄误差对0≤Th/U≤∝来说为±5.1％-±8.3％,对1.1≤Th/U≤9.5来说只有±2.5％％-±4.1％。     

The GNAQ T96S Mutation Affects Cell Signaling and Enhances the Oncogenic Properties of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), the most common malignant tumor in the liver, grows and metastasizes rapidly. Despite advances in treatment modalities, the five-year survival rate of HCC remains less than 30%. We sought genetic mutations that may affect the oncogenic properties of HCC, using The Cancer Genome Atlas (TCGA) data analysis. We found that the GNAQ T96S mutation (threonine 96 to serine alteration of the Gαq protein) was present in 12 out of 373 HCC patients (3.2%). To examine the effect of the GNAQ T96S mutation on HCC, we transfected the SK-Hep-1 cell line with the wild-type or the mutant GNAQ T96S expression vector. Transfection with the wild-type GNAQ expression vector enhanced anchorage-independent growth, migration, and the MAPK pathways in the SK-Hep-1 cells compared to control vector transfection. Moreover, cell proliferation, anchorage-independent growth, migration, and the MAPK pathways were further enhanced in the SK-Hep-1 cells transfected with the GNAQ T96S expression vector compared to the wild-type GNAQ-transfected cells. In silico structural analysis shows that the substitution of the GNAQ amino acid threonine 96 with a serine may destabilize the interaction between the regulator of G protein signaling (RGS) protein and GNAQ. This may reduce the inhibitory effect of RGS on GNAQ signaling, enhancing the GNAQ signaling pathway. Single nucleotide polymorphism (SNP) genotyping analysis for Korean HCC patients shows that the GNAQ T96S mutation was found in only one of the 456 patients (0.22%). Our data suggest that the GNAQ T96S hotspot mutation may play an oncogenic role in HCC by potentiating the GNAQ signal transduction pathway.     

Real-Time Monitoring the Effect of Cytopathic Hypoxia on Retinal Pigment Epithelial Barrier Functionality Using Electric Cell-Substrate Impedance Sensing (ECIS) Biosensor Technology

Disruption of retinal pigment epithelial (RPE barrier integrity is a hallmark feature of various retinal blinding diseases, including diabetic macular edema and age-related macular degeneration, but the underlying causes and pathophysiology are not completely well-defined. One of the most conserved phenomena in biology is the progressive decline in mitochondrial function with aging leading to cytopathic hypoxia, where cells are unable to use oxygen for energy production. Therefore, this study aimed to thoroughly investigate the role of cytopathic hypoxia in compromising the barrier functionality of RPE cells. We used Electric Cell-Substrate Impedance Sensing (ECIS) system to monitor precisely in real time the barrier integrity of RPE cell line (ARPE-19) after treatment with various concentrations of cytopathic hypoxia-inducing agent, Cobalt(II) chloride (CoCl₂). We further investigated how the resistance across ARPE-19 cells changes across three separate parameters: R_b (the electrical resistance between ARPE-19 cells), α (the resistance between the ARPE-19 and its substrate), and C_m (the capacitance of the ARPE-19 cell membrane). The viability of the ARPE-19 cells and mitochondrial bioenergetics were quantified with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and seahorse technology, respectively. ECIS measurement showed that CoCl₂ reduced the total impedance of ARPE-19 cells in a dose dependent manner across all tested frequencies. Specifically, the ECIS program’s modelling demonstrated that CoCl₂ affected R_b as it begins to drastically decrease earlier than α or C_m, although ARPE-19 cells’ viability was not compromised. Using seahorse technology, all three concentrations of CoCl₂ significantly impaired basal, maximal, and ATP-linked respirations of ARPE-19 cells but did not affect proton leak and non-mitochondrial bioenergetic. Concordantly, the expression of a major paracellular tight junction protein (ZO-1) was reduced significantly with CoCl_2-treatment in a dose-dependent manner. Our data demonstrate that the ARPE-19 cells have distinct dielectric properties in response to cytopathic hypoxia in which disruption of barrier integrity between ARPE-19 cells precedes any changes in cells’ viability, cell-substrate contacts, and cell membrane permeability. Such differences can be used in screening of selective agents that improve the assembly of RPE tight junction without compromising other RPE barrier parameters.     

Molecular dynamics model structures for the molten globule state of {alpha}-lactalbumin: aromatic residue clusters I and II

To model the molten globule structure of alpha.gif" ALT="{alpha}" BORDER="0">-lactalbumin, moleculardynamics (MD) simulations were carried out for the protein inexplicit water at high temperature. In these simulations, long-rangeCoulomb interactions were evaluated explicitly with an originalmethod (particle–particle and particle–cell: PPPC)to avoid artifacts caused by the cut-off. The MD simulationswere started from two initial conditions to verify that similarresults would be obtained. From the last 150 ps trajectoriesof the two MD simulations, two partially unfolded average structureswere obtained. These structures had the following common structuralfeatures which are characteristic of the molten globule state.The radii of gyration for these conformations were 7.4 and 9.6%larger than that of the native state. These values were almostthe same as the experimental value (9.6%) observed recentlyby small-angle X-ray scattering (Kataoka,M., Kuwajima,K., Tokunaga,F.and Goto,Y., 1997, Protein Sci., 6, 422–430). Furthermore,aromatic residues of clusters I and II in these structures werefar apart from each other except for Try103–Trp104. Thisresult is in good agreement with NMR experimental results forthe acid-denatured molten globule state (Alexandrescu et al.,1992, 1993); that is, NOE signals between the aromatic residueswere not observed, except for that of Try103–Trp104 inthe molten globule state. Other structural features of thesemodels for the molten globule state are discussed with referenceto native state structures.     

A holistic approach to protein structure alignment

A method of protein structure comparison developed previouslyis extended to incorporate other aspects of protein structurein addition to the inter-atomic vectors on which it was originallybased. Each additional aspect, which included hydrogen bonding,solvent exposure, torsional angles and sequence, was introducedseparately and evaluated for its ability to improve alignmentquality. The components were then combined, suitably weighted,to produce a more holistic comparison method. The method wastested on a group of remotely related ß/alpha.gif" ALT="{alpha}" BORDER="0"> type proteinsthat share a common feature in their overall chain fold. Theresults indicated that while the original inter-atomic vectorcomponent was sufficient to give the correct alignment of mostpairs of topologically equivalent proteins, the inclusion ofhydrogen bonds, torsion angles and a measure of solvent exposureled to improvements in the more difficult comparisons. Considerationof amino acid properties, including hydrophobicity, had no beneficialeffect. The failure of the latter component was not unexpectedconsidering the almost total lack of sequence similarity amongthe proteins considered.     

An infra-red study of model compounds of poly(tetramethylene terephthalate)

An infra-red spectroscopic investigation of the poly(tetramethylene terephthalate) model compounds butyl-dibenzoate: C₆H₅COO(CH₂)₄OCOC₆H₅ (i), 1,4-bis-butyl terephthalate: HO(CH₂)₄-OCO₆H₄COO(CH₂)₄-OH (ii), α-butyl-ω-butoxyterephthalaoyl-di-(tetramethylene terephthalate): H(CH₂)₄(OCOC₆H₄COO-(CH₂)₄-)₃-OH (iii), and α-butyl-ω-butoxyterephthalaoyl-tetra-(tetra-methylene terephthalate): HO(CH₂)₄-(OCOC₆H₄COO(CH₂)₄-)₅-OH (iv) is presented. The synthesis of (i) is also described. Spectroscopic evidence indicates that the crystal conformations of the aliphatic segments in (i) and (ii) closely resemble the extended all trans beta form of PTMT. Oligomers (iii) and (iv), however, are found to be more similar to the crumpled alpha crystal phase of PTMT.     

Role of primary and secondary protein structure in neurotransmitter receptor activation mechanisms

A proton transfer triggered by a ligand interacting with thereceptor had been suggested as the initial step in the activationof a receptor for the neurotransmitter serotonin (5-hydroxy-tryptamine;5-HT). To evaluate the role of the receptor macromolecule inmodulating the primary molecular event in ligand-mediated activation,the process of proton transfer was analysed in the environmentof a protein model for the 5-HT receptor. In the absence ofa detailed receptor structure, the enzyme actinidin was chosenas the model for the receptor based on criteria obtained fromstructure-activity considerations on the ligands. The firstsimulation of a mechanism for receptor activation was performedon this model using methods of theoretical chemistry to studythe effect of specific structural elements. The premise is thatthe role of the elements of secondary structure of soluble proteins(e.g. actinidin) in determining structure-function relationsin these macromolecules is maintained when these elements arepart of membrane-bound receptor proteins. Results from the calculationsof the effects of the six alpha helices of actinidin on theproton transfer process from the imidazolium side chain of His162 to the thiol side chain of Cys 25 in the protein show thatthe helices contribute in different ways to modulate the energyof proton transfer. The largest helix, Al, opposes the protontransfer through the effect of the helix dipole. The chargedresidues (primary structure) in helix A3 favor the proton transfer,and mask the effect of its helix dipole (secondary structure)which opposes the transfer. The direction of the proton transfersimulated for the activation mechanism is opposite to that assumedin the catalytic process of the thiol protease, and the entireprotein environment opposes the transfer. This supports thespecific role of the ligand in triggering the proton transferas a response to its binding.     

α-烯烃磺酸盐、NaCl、NH_4Cl对液体洗涤剂粘度影响的研究

研究了阴离子表面活性剂/非离子表面活性剂复配液体洗涤剂时α 烯烃磺酸盐、NaCl、NH4Cl对其粘度的影响。结果表明:液体洗涤剂中无论是否含有NaCl或NH4Cl,其粘度均随体系中α 烯烃磺酸盐浓度的增加而下降。NaCl或NH4Cl对液体洗涤剂粘度的提高程度与α 烯烃磺酸盐的浓度有关。对以α 烯烃磺酸盐为主体表面活性剂的液体洗涤剂,其粘度的提高与NaCl或NH4Cl的浓度有关。