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1.
Vibrational spectroscopy techniques can be applied to identify a susceptibility-to-adenocarcinoma biochemical signature. A sevenfold difference in incidence of prostate adenocarcinoma (CaP) remains apparent amongst populations of low- (e.g. India) compared with high-risk (e.g. UK) regions, with migrant studies implicating environmental and/or lifestyle/dietary causative factors. This study set out to determine the biospectroscopy-derived spectral differences between risk-associated cohorts to CaP. Benign prostate tissues were obtained using transurethral resection from high-risk (n = 11, UK) and low-risk (n = 14, India) cohorts. Samples were analysed using attenuated total reflection Fourier-transform infrared (FTIR) spectroscopy, FTIR microspectroscopy and Raman microspectroscopy. Spectra were subsequently processed within the biochemical cell region (1,800−1–500 cm–1) employing principal component analysis (PCA) and linear discriminant analysis (LDA) to determine whether wavenumber–absorbance/intensity relationships might reveal biochemical differences associated with region-specific susceptibility to CaP. PCA-LDA scores and corresponding cluster vector plots identified pivotal segregating biomarkers as 1,582 cm−1 (Amide I/II trough); 1,551 cm−1 (Amide II); 1,667 cm−1 (Amide I); 1,080 cm−1 (DNA/RNA); 1,541 cm−1 (Amide II); 1,468 cm−1 (protein); 1,232 cm−1 (DNA); 1,003 cm−1 (phenylalanine); 1,632 cm−1 [right-hand side (RHS) Amide I] for glandular epithelium (P < 0.0001) and 1,663 cm−1 (Amide I); 1,624 cm−1 (RHS Amide I); 1,126 cm−1 (RNA); 1,761, 1,782, 1,497 cm−1 (RHS Amide II); 1,003 cm−1 (phenylalanine); and 1,624 cm−1 (RHS Amide I) for adjacent stroma (P < 0.0001). Primarily protein secondary structure variations were biomolecular markers responsible for cohort segregation with DNA alterations exclusively located in the glandular epithelial layers. These biochemical differences may lend vital insights into the aetiology of CaP.  相似文献   

2.
Human flavin-containing monooxygenases are the second most important class of drug-metabolizing enzymes after cytochromes P450. Here we report a simple but functional and stable enzyme-electrode system based on a glassy carbon (GC) electrode with human flavin-containing monooxygenase isoform 3 (hFMO3) entrapped in a gel cross-linked with bovine serum albumin (BSA) by glutaraldehyde. The enzymatic electrochemical responsiveness is characterised by using well-known substrates: trimethylamine (TMA), ammonia (NH3), triethylamine (TEA), and benzydamine (BZD). The apparent Michaelis–Menten constant (KM) and apparent maximum current (Imax) are calculated by fitting the current signal to the Michaelis–Menten equation for each substrate. The enzyme-electrode has good characteristics: the calculated sensitivity was 40.9 ± 0.5 mA mol−1 L cm−2 for TMA, 43.3 ± 0.1 mA mol−1 L cm−2 for NH3, 45.2 ± 2.2 mA mol−1 L cm−2 for TEA, and 39.3 ± 0.6 mA mol−1 L cm−2 for BZD. The stability was constant for 3 days and the inter-electrode reproducibility was 12.5%. This is a novel electrochemical tool that can be used to investigate new potential drugs against the catalytic activity of hFMO3.  相似文献   

3.
 The fungicide triadimenol consists of a mixture of two diastereoisomers. Diastereoisomer A (1RS,2SR) could be obtained from the mixture by fractionated crystallization from ethanol/water and toluene, successively, whereas diastereoisomer B (1RS,2RS) could be separated by column chromatography on a silica gel column using ethylacetate as eluent. Four different crystal forms of diastereoisomer A could be derived. The modifications were characterized by means of thermal analysis (thermomicroscopy, DSC), FTIR-spectroscopy, FT-Raman-spectroscopy and powder X-ray diffraction, as well as pycnometry. The thermodynamic relationships are illustrated in a semischematic energy/temperature-diagram which provides information about the relative thermodynamic stabilities and physical properties of the four crystal forms. Mod. II (m.p. 132 °C, ΔHf 33.1±0.2 kJ mol−1, density 1.271±0.001 g cm−3) was obtained from toluene after the separation of diastereoisomer A and is enantiotropically related to mod. I (m.p. 138 °C, ΔHf 32.0 ± 0.2 kJ mol−1, density 1.243±0.001 g cm−3). The transition point of mod. II with mod. I was determined between 30 and 40 °C, which means that mod. II is thermodynamically stable at ambient conditions. Mod. III (m.p. 112 °C, ΔHf 25.1±0.5 kJ mol−1) and mod. IV were obtained from the melt. Furthermore, the phase diagrams of the binary systems of diastereoisomer B and the four modifications of diastereoisomer A were calculated by means of the experimentally obtained thermodynamical data. Received September 30, 1999. Revision July 30, 2000.  相似文献   

4.
Perovskite-type compounds, Li x La(1− x )/3NbO3 and (Li0.25La0.25)1− x Sr0.5 x NbO3 as lithium ionic conductors, were synthesized by a solid-state reaction. From powder X-ray diffraction, the solid solution ranges of the two compounds were determined to be 0≤x≤0.25 and 0≤x≤0.125, respectively. In the Li x La(1− x )/3NbO3 system, the ionic conductivity of lithium at room temperature, σ25, exhibited a maximum value of 4.7 × 10−5 S · cm−1 at x = 0.10. However, because of the decrease in the lattice parameters with increasing Li concentration , σ25 of the samples decreased with increasing x from 0.10 to 0.25. Also, in the (Li0.25La0.25)1− x Sr0.5 x NbO3 system, the lattice parameter increased with the increase of Sr concentration and the σ25 achieved a maximum (7.3 × 10−5 S · cm−1 at 25 °C) at x = 0.125. Received: 12 September 1997 / Accepted: 15 November 1997  相似文献   

5.
Relativistic energy-consistent small-core lanthanide pseudopotentials of the Stuttgart–Bonn variety and extended valence basis sets have been used for the investigation of the dimers La2 and Lu2. It was found that the ground states for La2 and Lu2 are most likely 1 g + g 2π u 4) and 3 g (4f 144f 14σ g 2σ u 2πu 2), respectively. The molecular constants including error bars were derived from multireference configuration interaction as well as coupled-cluster calculations, taking into account corrections for atomic spin–orbit splitting as well as possible basis set superposition errors. The theoretical values for La2 (R e=2.70±0.03 ?, D e=2.31±0.13 eV, ωe=186±13 cm−1) show good agreement with the experimental binding energy (D e=2.52±0.22 eV), but the experimental vibrational constant in an Ar matrix (ωe=236±0.8 cm−1) is significantly higher. For Lu2 the theoretical values (R e=3.07±0.03 ?, D e=1.40±0.12 eV, ωe=123±1 cm−1) are in overall excellent agreement with experimental data (D e=1.43±0.34 eV, ωe=122± 1 cm−1). The electronic structures of La2 and Lu2 are compared to those other lanthanide dimers and trends in the series are discussed. Received: 25 March 2002 / Accepted: 2 June 2002 / Published online: 21 August 2002  相似文献   

6.
This paper presents results from the European Commission-funded project Doncalibrant, the objective of which was to produce calibrators with certified mass fractions of the Fusarium toxins deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-Ac-DON), 15-acetyldeoxynivalenol (15-Ac-DON), and nivalenol (NIV), in acetonitrile. The calibrators, available in ampoules, were sufficiently homogeneous, with between-bottle variations (s bb) of less than 2%. Long-term stability studies performed at four different temperatures between −18 and 40 °C revealed no significant negative trends (at a confidence level of 95%). Molar absorptivity coefficients (in L mol−1 cm−1) were determined for all four toxins (DON: 6805 ± 126, NIV: 6955 ± 205, 3-Ac-DON: 6983 ± 141, 15-Ac-DON: 6935 ± 142) on the basis of a mini-interlaboratory exercise. The overall uncertainty of the calibrators’ target values for DON and NIV were evaluated on the basis of gravimetric preparation data and include uncertainty contributions from possible heterogeneity, storage, and transport. The Doncalibrant project resulted in the production of calibrators for DON (IRMM-315) and NIV (IRMM-316) in acetonitrile with certified mass fractions of 25.1 ± 1.2 μg g−1 and 24.0 ± 1.1 μg g−1, respectively. Both CRMs became commercially available from the Institute for Reference Materials and Measurements (IRMM, Geel, Belgium) at the beginning of 2007.  相似文献   

7.
We report quantitative infrared spectra of vapor-phase hydrogen peroxide (H2O2) with all spectra pressure-broadened to atmospheric pressure. The data were generated by injecting a concentrated solution (83%) of H2O2 into a gently heated disseminator and diluting it with pure N2 carrier gas. The water vapor lines were quantitatively subtracted from the resulting spectra to yield the spectrum of pure H2O2. The results for the ν6 band strength (including hot bands) compare favorably with the results of Klee et al. (J Mol. Spectrosc. 195:154, 1999) as well as with the HITRAN values. The present results are 433 and 467 cm-2 atm−1 (±8 and ±3% as measured at 298 and 323 K, respectively, and reduced to 296 K) for the band strength, matching well the value reported by Klee et al. (S = 467 cm−2 atm−1 at 296 K) for the integrated band. The ν1 + ν5 near-infrared band between 6,900 and 7,200 cm−1 has an integrated intensity S = 26.3 cm−2 atm−1, larger than previously reported values. Other infrared and near-infrared bands and their potential for atmospheric monitoring are discussed.  相似文献   

8.
Electrochemistry of water-soluble cobalt(II) tetrasulfophthalocyanine (CoTSPc) electrodeposited on glassy carbon nanotube pre-modified with acid-functionalized multi-walled carbon nanotubes (MWCNT) is described. Both charge transfer resistances toward [Fe(CN)6]3−/4− redox probe and electrocatalytic responses toward epinephrine (EP) detection follow the trend: bare GCE < GCE-MWCNT < GCE-CoTSPc < GCE-MWCNT-CoTSPc. EP analysis was then carried out in details using GCE-MWCNT-CoTSPc. The catalytic rate constant value k ch = 2.2 × 107 (mol cm−3)−1 s−1 was obtained from rotating disk electrode experiment. Interestingly, GCE-MWCNT-CoTSPc efficiently suppressed the detection of ascorbic acid (the natural interference of neurotransmitters in physiological conditions) showing good sensitivity (0.132 ± 0.003 A l mol−1), limit of detection (4.517 × 10−7 mol l−1), and quantification (15.056 × 10−7 mol l−1). In addition, GCE-MWCNT-CoTSPc was conveniently used to determine EP in epinephrine hydrochloric acid injection with recovery of 101.1 ± 2.2%.  相似文献   

9.
In this work, the potential of microwave-assisted alkali pretreatment in order to improve the rupture of the recalcitrant structures of the cashew able bagasse (CAB), lignocellulosic by-product in Brazil with no commercial value, is obtained from cashew apple process to juice production, was studied. First, biomass composition of CAB was determined, and the percentage of glucan and lignin was 20.54 ± 0.70% and 33.80 ± 1.30%, respectively. CAB content in terms of cellulose, hemicelluloses, and lignin, 19.21 ± 0.35%, 12.05 ± 0.37%, and 38.11 ± 0.08%, respectively, was also determined. Results showed that, after enzymatic hydrolysis, alkali concentration exerted influence on glucose formation, after pretreatment with 0.2 and 1.0 mo L−1 of NaOH (372 ± 12 and 355 ± 37 mg gglucan−1) when 2% (w/v) of cashew apple bagasse pretreated by microwave-assisted alkali pretreatment (CAB-M) was used. On the other hand, pretreatment time (15–30 min) and microwave power (600–900 W) exerted no significant effect on hydrolysis. On enzymatic hydrolysis step, improvement on solid percentage (16% w/v) and enzyme load (30 FPU gCAB-M−1) increased glucose concentration to 15 g L−1. The fermentation of the hydrolyzate by Saccharomyces cerevesiae resulted in ethanol concentration and productivity of 5.6 g L−1 and 1.41 g L−1 h−1, respectively.  相似文献   

10.
Relative enthalpies for low-and high-temperature modifications of Na3FeF6 and for the Na3FeF6 melt have been measured by drop calorimetry in the temperature range 723–1318 K. Enthalpy of modification transition at 920 K, δtrans H(Na3FeF6, 920 K) = (19 ± 3) kJ mol−1 and enthalpy of fusion at the temperature of fusion 1255 K, δfusH(Na3FeF6, 1255 K) = (89 ± 3) kJ mol−1 have been determined from the experimental data. Following heat capacities were obtained for the crystalline phases and for the melt, respectively: C p(Na3FeF6, cr, α) = (294 ± 14) J (mol K)−1, for 723 = T/K ≤ 920, C p(Na3FeF6, cr, β) = (300 ± 11) J (mol K)−1 for 920 ≤ T/K = 1233 and C p(Na3FeF6, melt) = (275 ± 22) J (mol K)−1 for 1258 ≤ T/K ≤ 1318. The obtained enthalpies indicate that melting of Na3FeF6 proceeds through a continuous series of temperature dependent equilibrium states, likely associated with the production of a solid solution.   相似文献   

11.
The effect of hydrostatic pressure below 1000 kg cm−2 on the rate of reactions of o-and p-nitrophenylsulfenyl chlorides with styrene and cyclohexene was studied. The activation and reaction volumes (cm3 mol−1) for the reactions of o-nitrophenylsulfenyl chloride with styrene in acetonitrile (−23.1 and −23.6), 1,2-dichloroethane (−29.2 and −24.7), chlorobenzene (no, −20.2), and anisole (−25.1 and −21.2) and for the reaction of p-nitrophenylsulfenyl chloride with styrene in carbon tetrachloride (−39.5±1.5 and −22.0) were determined. In carbon tetrachloride the activation volumes for the reactions of cyclohexene with o-and p-nitrophenylsulfenyl chlorides (−37.7±2.0 and −40.9±1.2 cm3 mol−1, respectively) are almost the same and coincide with the data for the reactions with styrene. The considerable decrease in the volume of the transition state in the nonpolar solvent is considered as a consequence of the enhanced electrostriction of carbon tetrachloride in the solvate sphere of the transition state of the reaction, which excludes the nonpolar transition state of the sulfuran type. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 477–480, March, 2007.  相似文献   

12.
Summary.  The van der Pauw method has been applied to conductivity relaxation experiments on YBa2Cu3O6+δ at 600°C in order to determine the chemical diffusion coefficient as a function of the oxygen partial pressure in the surrounding atmosphere (100 > p O 2/bar > 10−3). It is shown that the van der Pauw technique is suitable for monitoring the conductivity relaxation when the oxygen diffusion is perpendicular to the direct current flowing through the sample in accordance with the van der Pauw geometry using thin tablets as samples. The oxygen partial pressure is changed stepwise (generally Δlogp O 2 ≤ 0.5) by employing appropriate gas mixtures as well as an electrochemical oxygen pump device. An evaluation formula is given for the determination of the chemical diffusion coefficient neglecting slow surface processes. In addition, the electronic conductivity of YBa2Cu3O6+δ has been measured at 600°C as a function of oxygen partial pressure of the ambient atmosphere (100 > p O 2/bar > 10−5) by means of the van der Pauw method applying the same experimental set-up. Typical values of the chemical diffusion coefficient are in the range of 10−6 cm2·s−1; the results of the conductivity measurements are interpreted in terms of an appropriate defect model. Received May 30, 2000. Accepted June 8, 2000  相似文献   

13.
Numerical Hartree–Fock calculations of the first three coefficients of the MacLaurin expansion and the leading coefficient of the large-p asymptotic expansion of the electron momentum densities Π(p) are reported for 54 singly charged atomic cations from He+ (atomic number Z = 2) to Cs+ (Z = 55) and 43 anions from H (Z = 1) to I (Z = 53) in their experimental ground states. We also report all the finite moments <p k > (−2≤k≤+4) of the momentum densities Π(p) for the above-mentioned 97 ionic species. The results are compared with the previous ones for neutral atoms [Koga and Thakkar (1996) J Phys B 29: 2973], and the dependence of the expansion coefficients and moments on nuclear charge is discussed among isoelectronic species. Received: 20 November 1998 / Accepted: 15 January 1999 / Published online: 7 June 1999  相似文献   

14.
A-site-deficient perovskite cathode material La0.58Sr0.4Co0.2Fe0.8O3 − δ (L58SCF) is coated on the yttria-stabilized zirconia electrolyte by screen-printing technique. Several key fabrication parameters including selection of additives (binder and pore former), effect of coating thickness, sintering temperature and time on the microstructure, and electrochemical performance of cathode are investigated by scanning electron microscopy and electrochemical impedance spectroscopy. We study the microstructure and the electrochemical property of the cathode with different kinds of additives. Results show that the cathode possesses fine microstructure, enough porosity, and ideal electrochemical property when polyvinyl butyral serves as both binder and pore former in the cathode. The cathode with three screen-printing coats (thickness 28 ± 7 μm, weight 6.07 ± 0.72 mg cm−2) sintering at 1,000 °C for 2 h shows lower polarization resistance of 0.183 Ω cm2 at 800 °C. Based on the optimized parameters, the polarization resistances of the L58SCF–Ce0.8Gd0.2O1.9 – δ composite cathode display the R p values of 0.067 Ω cm2 at 800 °C, 0.106 Ω cm2 at 750 °C, 0.225 Ω cm2 at 700 °C, and 0.550 Ω cm2 at 650 °C.  相似文献   

15.
The temperature and pressure dependences of pK for acridine ion ionization were determined up to 200 °C and 2000 bar. The UV-Vis measurements at high temperatures and pressures were conducted in flow-through spectrophotometric cells. Two independent series of experiment were performed: one in a Ti–Pd cell with silica quartz windows for measurements in the ultraviolet region, and another in a Ti grade 5 cell with sapphire windows for use at higher pressures, which permitted measurements in the visible region. Combined chemometric and thermodynamic analyses of the UV-Vis spectrophotometric data were used to extract the ionization constants as well as the changes in molar volume ΔV° for acridine protonation as functions of temperature and pressure. Values of pK decrease from 5.52 to 3.74 with increasing temperature from 25 to 200 °C at saturated water-vapor pressure. The pressure dependence of acridinium ion ionization is small (e.g., pK=5.5 at 25 °C and 2000 bar) and is characterized by positive ΔV°≤1.2 cm3⋅mol−1, which is not surprising for this type of isocoulombic reaction involving a large molecule.  相似文献   

16.
A fast and sensitive liquid chromatography–mass spectrometry method was developed for the determination of ursolic acid (UA) in rat plasma and tissues. Glycyrrhetinic acid was used as the internal standard (IS). Chromatographic separation was performed on a 3.5 μm Zorbax SB-C18 column (30 mm × 2.1 mm) with a mobile phase consisting of methanol and aqueous 10 mM ammonium acetate using gradient elution. Quantification was performed by selected ion monitoring with (m/z) 455 for UA and (m/z) 469 for the IS. The method was validated in the concentration range of 2.5 − 1470 ng mL−1 for plasma samples and 20 − 11760 ng g−1 for tissue homogenates. The intra- and inter-day assay of precision in plasma and tissues ranged from 1.6% to 7.1% and 3.7% to 9.0%, respectively, and the intra- and inter-day assay accuracy was 84.2 − 106.9% and 82.1 − 108.1%, respectively. Recoveries in plasma and tissues ranged from 83.2% to 106.2%. The limits of detections were 0.5 ng mL−1 or 4.0 ng g−1. The recoveries for all samples were >90%, except for liver, which indicated that ursolic acid may metabolize in liver. The main pharmacokinetic parameters obtained were T max = 0.42 ± 0.11 h, C max = 1.10 ± 0.31 μg mL−1, AUC = 1.45 ± 0.21 μg h mL−1 and K a = 5.64 ± 1.89 h−1. The concentrations of UA in rat lung, spleen, liver, heart, and cerebellum were studied for the first time. This method is validated and could be applicable to the investigation of the pharmacokinetics and tissue distribution of UA in rats.  相似文献   

17.
Thin films of biodegradable corn starch-based biopolymer electrolytes were prepared by solution casting technique. Lithium hexafluorophosphate (LiPF6) and 1-butyl-3-methylimidazolium trifluoromethanesulfonate (BmImTf) were employed as lithium salt and ionic liquid, respectively. With reference to the temperature dependence study, Arrhenius relationship was observed. The highest ionic conductivity of (6.00 ± 0.01) × 10−4 S cm−1 was obtained at 80 °C. Based on x-ray diffraction (XRD) result, the peaks became broader with doping of ionic liquid revealing the higher amorphous region of the biopolymer electrolytes. Ionic liquid-based biopolymer electrolytes exhibited lower glass transition temperature (T g).  相似文献   

18.
To investigate the production of cellulases and xylanases from Penicillium echinulatum 9A02S1, solid-state fermentation (SSF) was performed by using different ratios of sugar cane bagasse (SCB) and wheat bran (WB). The greatest filter paper activity obtained was 45.82 ± 1.88 U gdm−1 in a culture containing 6SCB/4WB on the third day. The greatest β-glucosidase activities were 40.13 ± 5.10 U gdm−1 obtained on the third day for the 0SCB/10WB culture and 29.17 ± 1.06 U gdm−1 for the 2SCB/8WB culture. For endoglucanase, the greatest activities were 290.47 ± 43.57 and 276.84 ± 15.47 U gdm−1, for the culture 6SCB/4WB on the fourth and fifth days of cultivation, respectively. The greatest xylanase activities were found on the third day for the cultures 6SCB/4WB (36.38 ± 5.38 U gdm−1) and 4SCB/6WB (37.87 ± 2.26 U gdm−1). In conclusion, the results presented in this article showed that it was possible to obtain large amounts of cellulases and xylanases enzymes using low-cost substrates, such as SCB and WB.  相似文献   

19.
The effect of pH and neutral electrolyte on the interaction between humic acid/humate and γ-AlOOH (boehmite) was investigated. The quantitative characterization of surface charging for both partners was performed by means of potentiometric acid–base titration. The intrinsic equilibrium constants for surface charge formation were logK a,1 int=6.7±0.2 and logK a,2 int = 10.6±0.2 and the point of zero charge was 8.7±0.1 for aluminium oxide. The pH-dependent solubility and the speciation of dissolved aluminium was calculated (MINTEQA2). The fitted (FITEQL) pK values for dissociation of acidic groups of humic acid were pK 1 = 3.7±0.1 and pK 2 = 6.6±0.1 and the total acidity was 4.56 mmol g−1. The pH range for the adsorption study was limited to between pH 5 and 10, where the amount of the aluminium species in the aqueous phase is negligible (less than 10−5 mol dm−3) and the complicating side equilibria can be neglected. Adsorption isotherms were determined at pH ∼ 5.5, ∼8.5 and ∼9.5, where the surface of adsorbent is positive, neutral and negative, respectively, and at 0.001, 0.1, 0.25 and 0.50 mol dm−3 NaNO3. The isotherms are of the Langmuir type, except that measured at pH ∼ 5.5 in the presence of 0.25 and 0.5 mol dm−3 salt. The interaction between humic acid/humate and aluminium oxide is mainly a ligand-exchange reaction with humic macroions with changing conformation under the influence of the charged interface. With increasing ionic strength the surface complexation takes place with more and more compressed humic macroions. The contribution of Coulombic interaction of oppositely charged partners is significant at acidic pH. We suppose heterocoagulation of humic acid and aluminium oxide particles at pH ∼ 5.5 and higher salt content to explain the unusual increase in the apparent amount of humic acid adsorbed. Received: 20 July 1999 /Accepted in revised form: 20 October 1999  相似文献   

20.
Summary. We investigated empirical data for the vapor pressure (154≤T≤196 K) and the heat capacity (12.52≤T≤189.78 K) of solid carbon dioxide. A computer algebra system (CAS) was used for all calculations. From the numerical point of view, we have adopted a cubic piecewise polynomial representation for the heat capacity and reached an excellent agreement between the available empirical data and the calculated ones. Furthermore, we have obtained values for the vapor pressure and heat of sublimation at temperatures below 195 right down to 0 K. The theoretical key prerequisites are: 1) Determination of the heat of sublimation of 26250 J · mol−1 at vanishing temperature and 2) Elaboration of a ‘linearized’ vapor pressure equation that includes all the relevant properties of the gaseous and solid phases. It is shown that: 1) The empirical vapor pressure equation derived by Giauque & Egan remains valid below the assumed lower limit of 154 K (a similar argument holds for Antoine’s equation), 2) The heat of sublimation reaches its maximum value of 27211 J · mol−1 at 58.829 K and 3) The vapor behaves as a (polyatomic) ideal gas even for temperatures below 150 K.  相似文献   

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