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ABSTRACT: BACKGROUND: Genetic modification of the pig has been hampered by inefficiency of homologous recombination and unavailability of pig embryonic stem cells. Engineered zinc finger nuclease (ZFN)-mediated genetic modification in somatic cells combined with somatic cell nuclear transfer (SCNT) technology provides a new approach for targeted modification in pig genome. In this study, we used a ZFN pair to disrupt porcine α-1,3, galactosyltransferase (GGTA1) gene in liver-derived cells (LDC). ZFN-treated LDC were used as nuclear donors to produce fetuses and piglets via SCNT. All cloned fetuses and piglets showed biallelic knockout of GGTA1 gene. MATERIALS AND METHODS: A ZFN pair was designed to target exon 8 of pig GGTA1 gene. LDC were transfected with GGTA1 ZFN plasmids. SURVEYOR assay was used to evaluate the ZFN activity in LDC. GGTA1 gene knockout cells (GTKO) were obtained by counter-selection and used as nuclear donors for SCNT. The cloned fetuses and piglets were characterized by DNA sequencing. Expression of α-Gal epitope was further examined by flow cytometry and confocal microscopy. RESULTS: SURVEYOR assay revealed 6.48% ZFN activity in LDC. GTKO cells were obtained by counter-selection 10 d after ZFN transfection. A total of six fetuses and 13 piglets were produced by SCNT. All fetuses and piglets had biallelic mutations in the ZFN targeted region and were negative for α-Gal epitope. CONCLUSIONS: Biallelic GGTA1 gene disruption in LDC was generated efficiently by ZFN. GTKO fetuses were produced from ZFN-treated LDC by SCNT. GTKO piglets were obtained by SCNT of ZFN-treated LDC or recloning of fetal fibroblasts from GTKO fetuses. With longer lifespan and robust growth rate, LDC has the potential to endure multiple genetic modifications in vitro without going to SCNT, which could accelerate the production of genetically modified pig organs for xenotransplantation.
Journal of Surgical Research 07/2012; · 2.25 Impact Factor
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ABSTRACT: Trace constituents are widely present in complex mixtures, and trace analysis is challenging because of the unpredictable matrix. In this work, a high-component filtering strategy was developed for improved analysis of trace constituents in complex sample by liquid chromatography-mass spectrometry (LC-MS). Using a specifically designed chromatographic apparatus, the high-abundant fractions were filtered prior to LC-MS analysis. The samples complexity was reduced and the sample-loading amount for the rest low-level fractions can be considerably increased. The application of this approach was illustrated with an analytically challenging sample, a traditional Chinese herbal medicine named Compound Danshen Sample. We observed that the loss rate for 12 analytes during the filtering procedure ranged from 6.54 to 26.11%, but showed a stable repeatability with RSD<3.79%. The proposed filtering method with quadrupole time-of-flight mass spectrometritry (Q-TOF/MS) enhanced the detection capacity, offering a comprehensive characterization of 133 compounds in Compound Danshen Samples. The quantification sensitivity was also improved in trace analysis, allowing six low compounds that cannot be quantified by the traditional methods to be tested by the filtering method. It can be predicted that the qualitative and quantitative trace analysis will be greatly improved when the loading samples is increased resulting from the filtration of high-level targets. The proposed strategy is promising to monitor trace constituents in diverse complex mixtures in the analytical field of pharmaceutics, metabonomics and environments.
Journal of pharmaceutical and biomedical analysis 06/2012; 70:169-77. · 2.45 Impact Factor
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Hongwang Wang,
Tej B. Shrestha,
Matthew T. Basel,
Raj K. Dani,
Gwi-Moon Seo,
Sivasai Balivada,
Marla M. Pyle,
Heidy Prock,
Olga B. Koper,
Prem S. Thapa,
David Moore, Ping Li,
Viktor Chikan,
Deryl L. Troyer,
Stefan H. Bossmann
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ABSTRACT: The targeted delivery of therapeutics to the tumor site is highly desirable in cancer treatment, because it is capable of minimizing
collateral damage. Herein, we report the synthesis of a nanoplatform, which is composed of a 15 ± 1 nm diameter core/shell
Fe/Fe3O4 magnetic nanoparticles (MNPs) and the topoisomerase I blocker SN38 bound to the surface of the MNPs via a
carboxylesterase cleavable linker. This nanoplatform demonstrated high heating ability (SAR = 522 ± 40 W/g) in an AC-magnetic
field. For the purpose of targeted delivery, this nanoplatform was loaded into tumor-homing double-stable RAW264.7 cells (mouse
monocyte/macrophage-like cells (Mo/Ma)), which have been engineered to express intracellular carboxylesterase (InCE) upon
addition of doxycycline by a Tet-On Advanced system. The nanoplatform was taken up efficiently by these tumor-homing cells.They showed low toxicity even at high nanoplatform concentration. SN38 was released successfully by switching on the Tet-On Advanced system. We have demonstrated that this nanoplatform can be potentially used for thermochemotherapy. We will be able to achieve the following goals: (1) Specifically deliver the SN38 prodrug and magnetic nanoparticles to the cancer site as the payload of tumor-homing double-stable RAW264.7 cells; (2) Release of chemotherapeutic SN38 at the cancer site by means of the self-containing Tet-On Advanced system; (3) Provide localized magnetic hyperthermia to enhance the cancer treatment, both by killing cancer cells through magnetic heating and by activating the immune system.
Beilstein J. Nanotechnology. 06/2012; 3:444-455.
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Hongwang Wang,
Tej B. Shrestha,
Matthew T. Basel,
Raj K. Dani,
Gwi-Moon Seo,
Sivasai Balivada,
Marla M. Pyle,
Heidy Prock,
Olga B. Koper,
Prem S. Thapa,
David Moore, Ping Li,
Viktor Chikan,
Deryl L. Troyer,
Stefan H. Bossmann
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ABSTRACT: Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer.
Beilstein J. Nanotechnol. 01/2012; 3:444-455.
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ABSTRACT: The environment of Guizhou province of SW China is in part significantly impacted by mercury (Hg) mining activ-ities. The exploitation and processing of Hg-bearing ore in the past have led to multiple sources of Hg contamina-tion, including unprocessed ores and Hg waste calcines and liquid elemental Hg, making source control strategies difficult and expensive to implement. In this study, initially extended X-ray absorption fine structure (EXAFS) spec-troscopy was used to determine the Hg species and to estimate the relative proportions of these species present in Hg-bearing wastes from the Wanshan Hg mine (WSMM) of the eastern Guizhou province. The results showed that cinnabar is the dominant Hg species in the unroasted ore samples, while the most prevalent Hg compounds in mine waste calcine is in the following order: meta-cinnabar, cinnabar and mercuric chloride. Our study demonstrated that mass dependent fractionation of Hg isotopes may occur during transformation of cinnabar to by-products (such as meta-cinnabar and mercuric chloride) by the roasting process. Hg stable isotope analysis of unroasted Hg ores and Hg waste calcines showed that Hg waste calcines (0.08 ±0.20‰, 2ó, n=11) were enriched by ~0.80‰ in δ 202 Hg values compared to the unroasted Hg ores (−0.74 ±0.11‰, 2ó, n=14). Finally, using a com-bined triple mixing model, the source attribution of the downstream sediment in WSMM was estimated. Our study suggested that the Hg isotope could be a useful tool to trace and quantify the source of Hg in the environment.
Chemical Geology 01/2012; · 3.52 Impact Factor
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Hongwang Wang,
Tej B Shrestha,
Matthew T Basel,
Raj Kumar Dani,
Gwi-Moon Seo,
Sivasai Balivada,
Marla M Pyle,
Heidy Prock,
Olga B Koper,
Prem S Thapa,
David Moore, Ping Li,
Viktor Chikan,
Deryl L Troyer,
Stefan H Bossmann
[show abstract]
[hide abstract]
ABSTRACT: The targeted delivery of therapeutics to the tumor site is highly desirable in cancer treatment, because it is capable of minimizing collateral damage. Herein, we report the synthesis of a nanoplatform, which is composed of a 15 ± 1 nm diameter core/shell Fe/Fe(3)O(4) magnetic nanoparticles (MNPs) and the topoisomerase I blocker SN38 bound to the surface of the MNPs via a carboxylesterase cleavable linker. This nanoplatform demonstrated high heating ability (SAR = 522 ± 40 W/g) in an AC-magnetic field. For the purpose of targeted delivery, this nanoplatform was loaded into tumor-homing double-stable RAW264.7 cells (mouse monocyte/macrophage-like cells (Mo/Ma)), which have been engineered to express intracellular carboxylesterase (InCE) upon addition of doxycycline by a Tet-On Advanced system. The nanoplatform was taken up efficiently by these tumor-homing cells. They showed low toxicity even at high nanoplatform concentration. SN38 was released successfully by switching on the Tet-On Advanced system. We have demonstrated that this nanoplatform can be potentially used for thermochemotherapy. We will be able to achieve the following goals: (1) Specifically deliver the SN38 prodrug and magnetic nanoparticles to the cancer site as the payload of tumor-homing double-stable RAW264.7 cells; (2) Release of chemotherapeutic SN38 at the cancer site by means of the self-containing Tet-On Advanced system; (3) Provide localized magnetic hyperthermia to enhance the cancer treatment, both by killing cancer cells through magnetic heating and by activating the immune system.
Beilstein Journal of Nanotechnology 01/2012; 3:444-55. · 0.79 Impact Factor
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11/2011; , ISBN: 978-953-307-420-7
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Xun Chu,
Chun-Ming Pan,
Shuang-Xia Zhao,
Jun Liang,
Guan-Qi Gao,
Xiao-Mei Zhang,
Guo-Yue Yuan,
Chang-Gui Li,
Li-Qiong Xue,
Min Shen, [......],
Gang Chen,
Qing Su,
Yong-De Peng,
Jia-Jun Zhao,
Guang Ning,
Zhu Chen,
Jia-Lun Chen,
Sai-Juan Chen,
Wei Huang,
Huai-Dong Song
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ABSTRACT: Graves' disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves' disease, we conducted a genome-wide association study in 1,536 individuals with Graves' disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls. We confirmed four previously reported loci (in the major histocompatibility complex, TSHR, CTLA4 and FCRL3) and identified two new susceptibility loci (the RNASET2-FGFR1OP-CCR6 region at 6q27 (P(combined) = 6.85 × 10(-10) for rs9355610) and an intergenic region at 4p14 (P(combined) = 1.08 × 10(-13) for rs6832151)). These newly associated SNPs were correlated with the expression levels of RNASET2 at 6q27, of CHRNA9 and of a previously uncharacterized gene at 4p14, respectively. Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves' disease.
Nature Genetics 08/2011; 43(9):897-901. · 35.53 Impact Factor
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ABSTRACT: Fibrous carbon nanofiber composite is prepared by growing carbon nanofibers on graphite felt. Pressure drop experiments are carried out with ethanol solution to study the influence of the liquid surface tension on the permeability of the composite, and residence time distribution experiments with cyclohexane and water respectively are performed to study the effect of the fluid wettability on the flow behavior in the composite. Piston dispersion exchange (PDE) model is employed to determine the dynamic liquid holdup, the axial dispersion, and the mass transfer between the dynamic and static liquids. When the fluid is less oleophilic, less space in the CNF layer will be open for the flow, and the fluid will be more likely to slip over the carbon surface. Compared with the flow in spherical particle packing and in monolith, the mass transfer in the composite is high owing to its fibrous structure that splits the fluid into streamlets. The rate of mass transfer in water is lower than that in cyclohexane because water is only trapped in some of the large pores in the CNF layer while cyclohexane suffuses the whole layer.
07/2011;
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David R Tribble,
Nicholas G Conger,
Susan Fraser,
Todd D Gleeson,
Ken Wilkins,
Tanya Antonille,
Amy Weintrob,
Anuradha Ganesan,
Lakisha J Gaskins, Ping Li, [......],
Duane R Hospenthal,
Eugene V Millar,
Lorne H Blackbourne,
James R Dunne,
David Craft,
Katrin Mende,
Glenn W Wortmann,
Rachel Herlihy,
Jay McDonald,
Clinton K Murray
The Journal of trauma 07/2011; 71(1 Suppl):S33-42. · 2.48 Impact Factor
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ABSTRACT: Sodium metaborate hydrates are a class of compounds represented by the stoichiometry NaBO2·xH2O. Recently, sodium metaborate has received attention as the byproduct of sodium borohydride hydrolysis, a reaction that is under consideration for hydrogen storage applications. The aim of this work was to understand the disposition of water in the crystal structure of hydrated sodium metaborates and to characterize the thermal stability and dehydration of the various hydrated species to optimize hydrogen storage efficiency as well as recyclability of the borate. Observations from a suite of analytical techniques including thermal analyses (thermogravimetric analysis/differential scanning calorimetry), X-ray diffraction, and Raman spectroscopy were correlated to characterize the dehydration mechanism of commercially available sodium metaborates, with an emphasis on the dihydrate (x = 2). A transformation from tetrahedrally coordinated boron to trigonal boron occurs when NaB(OH)4 (x = 2) is heated between 25 and 400 °C. The first dehydration to Na3[B3O5(OH)2] (x = 1/3) releases 5 mol of water between 83 and 155 °C. The final mole of water is released between 249 and 280 °C, and Na3B3O6 (x = 0) is formed. Raman spectra are reported for x = 2 and 1/3 for the first time. First-principles density functional theory was used to compute Raman spectra of the x = 1/3 and 2 material in order to assign the modes. We found reasonably good agreement between the experimentally measured and calculated vibrational frequencies.
05/2011;
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ABSTRACT: In this study, on the basis of simulation of the electric field, the design optimization methods for 120 and 250 kA magnesium electrolysis cells were developed. A 3D numerical model was built to simulate the electric field at the steady state to obtain the minimum resistance voltage which has a significant effect on the energy consumption in the magnesium electrolysis process. The major optimization was focused on adjustment of structural parameters, such as the relative positions of the anode and cathode, electrolyte height in the cell, and so on. An orthogonal design approach was used to optimize the structural parameters in a 120 kA cell, and the optimization criterion was applied to magnify the design of a 250 kA cell. The resistance voltage in the optimized 250 kA cell was computed, and the minimum resistance voltage was 1631.3 mV among the provided solutions. Hence, the developed model and simulation results would be useful for the design optimization of a magnesium electrolysis cell.
04/2011;
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ABSTRACT: Two pure hydrated alkali borates, Na6[B4O5(OH)4]3·8H2O and K4[B10O15(OH)4], have been synthesized under mild hydrothermal conditions and characterized by single X-ray diffraction, infrared spectra, thermogravimetric analysis, differential thermal analysis, and chemical analysis. The enthalpies of solution of Na6[B4O5(OH)4]3·8H2O and K4[B10O15(OH)4] in 1 mol·L−1 HCl(aq) were measured to be (53.37 ± 0.09) kJ·mol−1 and (46.61 ± 0.15) kJ·mol−1. With the incorporation of the previously determined enthalpies of solution of H3BO3(s) in 1 mol·L−1 HCl(aq) and of NaCl(s) and KCl(s) in (HCl + H3BO3) aqueous solution, together with the standard molar enthalpies of formation of NaCl(s), KCl(s), H3BO3(s), HCl(aq), and H2O(l), the standard molar enthalpies of formation were found to be −(14093.0 ± 9.7) kJ·mol−1 for Na6[B4O5(OH)4]3·8H2O and −(8651.0 ± 8.1) kJ·mol−1 for K4[B10O15(OH)4] by solution calorimetry.
12/2010;
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ABSTRACT: A selective recursive kernel learning-based (SRKL) adaptive predictive controller is proposed for nonlinear time-varying processes. First, a SRKL identification model is presented with an efficient sparsification strategy which makes a trade-off between the tracking precision and the controller’s complexity. The SRKL model can be updated efficiently by introducing and/or deleting a sample via recursive learning algorithms. Consequently, the model can adjust its structure adaptively to capture the process dynamics and time-varying characteristics. On the basis of the SRKL model, a predictive controller with an adaptive modification item is designed. The novel controller can achieve better performance since the SRKL model can trace the process characteristics online. The obtained results on a laboratory-scale liquid-level process and a continuous bioreactor with time-varying parameters show that the proposed controller is superior to the traditional proportional-integral-derivative (PID) controller and related controller with an offline KL model without online updating.
09/2010;
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ABSTRACT: The multiphase transport phenomena frequently take place in metallurgical processes, for example, in the electrolysis process of magnesium, where there exists three-phase flow including liquid magnesium, molten electrolyte, and chlorine gas under the electromagnetic field. In this paper, the three-phase flow behaviors under the electromagnetic field in the advanced diaphragmless electrolytic cell were investigated by CFD simulation. The governing equations of the internal flow field in the electrolytic cell were established, where the standard k−e turbulence model and the VOF multiphase flow model were adopted for the comprehensive description of the flow characteristics of multiphase flow in the electrolytic cell, and the Lorentz force was added to the momentum equation of fluids as the momentum source term to combine the effect of electromagnetic field with the flow field. The order coupling method was adopted for the calculation of the coupled field. The numerical simulation on the three-phase flow field considering the effect of electromagnetic field was done using FLUENT6.3 software, the numerical simulations on the electric field and the magnetic field were carried out using Ansys 11.0 software, respectively, and the connection between the finite element software ANSYS and the control volume software Fluent was built using the user-defined function (UDF). According to the analysis on the distributions of the electromagnetic field and the flow field, the optimum flow circulation in the advanced diaphragmless electrolytic cell was obtained, which is very helpful for the design in the electrolysis process of molten magnesium salt.
08/2010;
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ABSTRACT: A simple nonlinear control strategy using sparse kernel learning (SKL) with a polynomial kernel form is presented and applied to chemical processes. The nonlinear process is first identified by SKL with a polynomial kernel, and then a predictive control performance index is formulated. This index is characterized as an even-degree polynomial function of the manipulated input and has the benefit that the input can be separated from the index because of its special structure. Consequently, the optimal manipulated input can be efficiently obtained by solving a simple root problem of an odd-degree polynomial equation. Moreover, the control parameter directly relates to its performance and can be tuned in a guided manner. All these attributes result in a practicable solution for real-time process control. The novel controller is applied to two chemical processes to evaluate its performance. The obtained results show the superiority of the proposed method compared to a well-tuned proportional−integral−derivative controller in different situations.
07/2010;
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ABSTRACT: Kinetic study of H2 oxidation in the preferential oxidation (PROX) of CO was implemented over a nanosize Au/CeO2 catalyst in a temperature range 313−353 K. The Langmuir−Hinshelwood mechanism was proposed to be mainly responsible for H2 oxidation, and CO oxidation can be accelerated by coadsorbed H at low temperatures. On the other hand, the water in the system has proved to suppress both CO and H2 oxidation by increasing the energy bars. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) of CO adsorption on the Au surface indicates that linear CO−Au bond can be weakened in the presence of H2; meanwhile, water can be a poison taking effects via the bonding of water and the lattice oxygen at the interface of Au/CeO2. The irreversible loss of activity during reaction may be caused by the reconstruction of Au particles, at least in part.
03/2010;
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ABSTRACT: Carbon nanofibers (CNFs) are grown on graphite fiber felt with a desired shape and dimension to form a structured carbon nanofiber composite. This CNF composite has a bimodal porous structure, containing macropores due to the intertexture of graphite fibers and mesopores due to the intertwist of CNFs. The pressure drop of the composite is derived from the convective flow of fluid through the macropores and is independent of the mesopores. Both viscous and turbulent resistance increases with the CNF’s loading. After being wetted with cyclohexane and dried in the air, the CNF’s layer shrinks and becomes smoother, and the composite has a much smaller viscous and turbulent resistance for the fluid. An extended Ergun equation is developed and is shown to be able to predict very well the pressure drop from the structural parameters that are related to the CNF’s loading, i.e., macropore porosity and expanded diameter of the graphite fibers.
02/2010;
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Qin-Yun Ma,
Chun-Lin Zuo,
Jun-Hua Ma,
Xiao-Na Zhang,
Ying Ru, Ping Li,
Chun-Ming Pan,
Zhi Liu,
Huang-Ming Cao,
Ming-Dao Chen,
Huai-Dong Song
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ABSTRACT: Mimecan is a protein of unknown function that is expressed in the pituitary. The aim of this study is to clarify the regulation and intracellular localisation of mimecan gene expression in the pituitary. With immunohistochemistry, we observed that mimecan protein was co-expressed with ACTH in pituitary corticotroph cells. Northern and Western blot analyses revealed that mimecan expression and secretion in corticotroph cells were up-regulated by treating AtT-20 cells with glucocorticoid. Meanwhile, mimecan expression in rat primary culture pituitary cells was also promoted by glucocorticoid. Co-incubation of AtT-20 cells with RU486 and glucocorticoid completely reversed the induction of mimecan gene expression by glucocorticoid. In addition, luciferase reporter assays showed that the -1474/+43 promoter region of mimecan was sufficient for glucocorticoid-responsive mimecan expression. These data collectively suggest that mimecan expressed in pituitary corticotroph cells is increased by glucocorticoid and that the up-regulation may be mediated by the classical GR pathways.
Molecular and Cellular Endocrinology 02/2010; 321(2):239-44. · 4.19 Impact Factor
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ABSTRACT: A new lithium borate Li3B5O8(OH)2 (I), which is the enantiomer of the known Li3B5O8(OH)2 (II), has been synthesized under mild hydrothermal conditions. Its crystal structure was determined from single crystal X-ray diffraction (XRD) data, further characterized by Fourier transform infrared (FT-IR) spectroscopy, Raman spectroscopy, XRD, differential thermal/thermogravimetric analysis (DTA-TG), and chemical analysis. It belongs to the tetragonal system, space group P43212, with a = 6.8506(9) Å, c = 14.5601(15) Å, V = 683.32(15) Å3, and Z = 4. Through an appropriate thermochemical cycle, the standard molar enthalpy of formation of Li3B5O8(OH)2 was determined to be −(4724.1 ± 4.2) kJ·mol−1 by solution calorimetry. Comparison of the experimental results with that of its enantiomer shows that the pair of enantiomers have the same standard molar enthalpy of formation like many other properties.
01/2010;
