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Purpose: Our previous study indicated that mitochondrial DNA (mtDNA) damage and mutations are crucial to the progressive loss of retinal ganglion cells (RGCs) in a glaucomatous rat model. In this study, we examined whether high pressure could directly cause mtDNA alterations and whether the latter could lead to mitochondrial dysfunction and RGC death. Methods: Primary cultured rat RGCs were exposed to 30 mm Hg of hydrostatic pressure (HP) for 12, 24, 48, 72, 96 and 120 h. mtDNA alterations and mtDNA repair/replication enzymes OGG1, MYH and polymerase gamma (POLG) expressions were also analyzed. The RGCs were then infected with a lentiviral small hairpin RNA (shRNA) expression vector targeting POLG (POLG-shRNA), and mtDNA alterations as well as mitochondrial function, including complex I/III activities and ATP production were subsequently studied at appropriate times. Finally, RGC apoptosis and the mitochondrial-apoptosis pathway-related protein cleaved caspase-3 were detected using a Terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and western blotting, respectively. Results: mtDNA damage was observed as early as 48 h after the exposure of RGCs to HP. At 120 h after HP, mtDNA damage and mutations significantly increased, reaching >40% and 4.8 ± 0.3-fold, respectively, compared with the control values. Twelve hours after HP, the expressions of OGG1, MYH and POLG mRNA in the RGCs were obviously increased 5.02 ± 0.6-fold (p < 0.01), 4.3 ± 0.2-fold (p < 0.05), and 0.8 ± 0.09-fold (p < 0.05). Western blot analysis showed that the protein levels of the three enzymes decreased at 72 and 120 h after HP (p < 0.05). After interference with POLG-shRNA, the mtDNA damage and mutations were significantly increased (p < 0.01), while complex I/III activities gradually decreased (p < 0.05). Corresponding decreases in membrane potential and ATP production appeared at 5 and 6 days after POLG-shRNA transfection respectively (p < 0.05). Increases in the apoptosis of RGCs and cleaved caspase-3 protein expression were observed after mtDNA damage and mutations. Conclusions: High pressures could directly cause mtDNA alterations, leading to mitochondrial dysfunction and RGC death.

Based on the crystal structure and the DFT calculation of Bi

The products of piperazine-directed synthesis of two-dimensional (20) aluminophosphates, AP2pip and AIPO-CJ9, that were crystallized under different conditions for different periods of time were freeze-dried and characterized using XRD and NMR techniques. The core units of the layered aluminophosphates including AP2pip, AIPO-CJ9, and L-DAP, which was hydrothermally synthesized in the presence of racemic 1,2-diaminopropane, were obtained by applying a "reverse evolution" process to their structures. The factors affecting the structure-directing ability of piperazine under acidic and basic conditions were analyzed. The cooperative role of water in directing the layered aluminophosphate of AP2pip under acidic conditions is discussed. After a thorough analysis of the core units of AIPO-CJ9 and L-DAP, a new phenomenon of a "topological-structure-directing effect" or a "topological-templating effect" was observed. The observation of the new phenomenon of a topological-structure-directing effect or a topological-templating effect may contribute to a deeper understanding of the nature or origin of the "structure-directing or templating effect". (C) 2012 Elsevier Inc. All rights reserved.

At a temperature over the decomposition point (375 °C) of MgH2, the formation of Mg2Ni is greatly enhanced from the 2MgH2+Ni system, as compared to the 2Mg+Ni system. In support of this finding, in-situ observation of X-ray absorption fine structure of the two systems indicates that MgNi bonds form faster in the 2MgH2+Ni system than in the 2Mg+Ni system. Furthermore, theoretical modeling also shows that Mg atoms are readily released from MgH2 using much less energy and thus are more available to react with Ni once the dehydrogenation of MgH2 occurs, as compared to normal Mg.

The adsorption of ethanol vapor on a mica surface at 298 K and different relative humidities (RHs) are studied using grand canonical Monte Carlo and molecular dynamics simulations. The simulations show that the adsorbed ethanol molecules form a monolayer on the mica surface, sharply contrasting the behavior of water, which forms multiple adsorption layers on the mica surface. Simulations of an ethanol and water mixture reveal that the adsorbed molecules are segregated into a water-rich domain near the mica surface and an ethanol-rich domain on top of the water-rich domain. The water-rich domain exhibits multilayers unless the RH is extremely low (

Thermal conductivities of graphene-like silicon and carbon hybrid nanostructures with silicon atom percentages varying from 0 % (graphene) to 100 % (silicene) are investigated using the reserve non-equilibrium molecular dynamic (RNEMD) method and Tersoff bond order potentials. The thermal conductivity of graphene is dramatically reduced with increasing silicon concentration, and the reduction appears to be related more to the topological structures formed than the amount of doped silicon atoms present. The reduction is collectively contributed to by reduced phonon group velocities (v), phonon free paths (l∞), and the specific heat capacity (c) of the material. For systems with high symmetry, thermal conductivity is mainly influenced by v and c. For systems with low symmetry, thermal conductivity is dominated by l∞; such materials are also more direction-dependent on thermal flux than highly symmetric materials.

The products of microporous aluminophosphate AlPO4-11 crystallized for different periods of time were freeze-dried and characterized by XRD and NMR techniques. Six crystallographically distinct Al- and P-centered large fragments and 34 small fragments of dimer (Al-P), trimer (Al-P-Al and P-Al-P), tetramer (Al-P-3 and P-Al-3). pentamer (Al-P-4 and P-Al-4), and 4- and 6-membered rings were extracted from the framework of AlPO4-11. Each of the six large fragments contained two completed coordination layers surrounding the centered atom. The shielding tensors of the Al and P atoms of the fragments were calculated using the quantum mechanics density functional theory. The experimentally observed chemical shifts of Al or P from the well-crystallized AlPO4-11 were assigned to the shielding tensors of the center atoms of the six large fragments and were further used as references in the determination of the chemical shifts of the Al or P atoms in the small fragments. A comparison of the calculated chemical shifts of the Al and P atoms in the small fragments to the experimental data of the products isolated at different crystallization periods suggested that the fragments of dimers, trimers of the form Al-P-Al, tetramers of the form P-Al-3, and pentamers may exist in the crystallization process of AlPO4-11. On the basis of these observations regarding the putative small fragments, a possible crystallization process of AlPO4-11 was proposed. (C) 2011 Elsevier Inc. All rights reserved.

A ReaxFF force field has been extended and used in the present work to simulate methanol to olefin (MTO) reactions in H-ZSM-5 zeolite. By explicitly considering multibody interactions and thermodynamic conditions, the initial reaction network of MTO in acidic zeolite has been obtained. New reaction mechanisms are proposed based on the simulations. For the activation of methanol, a less possible but very important CH3 radical mechanism is identified in addition to the commonly accepted methoxyl mechanism. The commonly accepted chain-growth mechanism, in which ethene interacts with methyloxide, has been observed. However, it is a small contribution to the total production. The more popular route for the chain growth is attributed to the presence of deprotonated Bronsted sites, which are produced via the activation of methanol molecules. Therefore, the hydrocarbon pool is working with the methanol molecules involved. With the hydrocarbon pool, the chain growth is significantly accelerated. Considering the co...

Molecular dynamics (MD) simulations were applied to investigate the liquid–liquid equilibria of water and dipropylene glycol dimethyl ether (DMM) based on all-atom OPLS force fields and simple point charge (SPC) water model. The default combining rules (geometric means) for describing interactions between water and ether molecules were modified by fitting hydration free energies of dimethyl ether and diethyl ether. The difference of Gibbs free energies (ΔG) was calculated using the thermodynamic integration (TI) method. Extensive simulations were carried out in order to reach high precision in the predicted free energies. The average uncertainties in calculated ΔG are 0.8 kJ/mol for DMM and 0.3 kJ/mol for water. From the calculated ΔGmix, the mutual solubility of the binary mixture was predicted using the double tangent method at four temperatures ranging from 283 K to 353 K and 1 atm.

The purpose of this study was to quantify the topographic distribution of bulbar conjunctival microlymphatic vessels in the monkey. Sixteen eyes from 8 rhesus monkeys were used. Full thickness pieces of globe wall were excised from each quadrant. Cryosections were stained for 5′-nucleotidase, an enzyme histochemical staining for lymphatic vessels, or vascular endothelial growth factor receptor-3, an immunohistochemical marker for the identification of lymphatic endothelial cells, and then counterstained by hematoxylin. The remaining bulbar conjunctiva was dissected and flat mounted. The tissue was then processed with 5′-nucleotidase and alkaline phosphatase, an enzyme histochemical stain with higher activity in blood vessels. Microscope images were further analysed by image processing. The density of lymphatics, diameter of lymphatic vessels, and the size of the drainage zone of each blind end of the initial lymphatics were studied. Conjunctival lymphatics consisted of initial lymphatics and pre-collectors. The initial lymphatics with blind ends were predominately distributed just under the epithelium. The density of these lymphatics (∼50%) and the drainage zone area (∼0.81 mm2) was similar in each quadrant, with no difference in the limbus and fornix regions. The average diameter of lymphatic vessels in each quadrant ranged from 82 to 111 μm, and was greater in the superior and nasal regions. Larger calibre pre-collectors with valve-like structures were mostly located sub Tenon’s membrane and predominantly located in the region mid-way between the limbus and fornix. There was a marked depth difference in initial lymphatic distribution, with the initial lymphatics mostly confined to the region between Tenon’s membrane and the conjunctival epithelium. Detailed knowledge of the topographic distribution of conjunctival lymphatics have significant relevance to a better understanding of immunology, drug delivery, glaucoma filtration surgery, and tumour metastasis in the conjunctiva.

Molecular simulation, as a powerful tool for investigating science of matter at a molecular level, is widely applied in interdisciplinary fields between chemistry, physics, biology, engineering and...

To evaluate the effect of acupuncture on rabbit tear secretion and compare the difference in tear protein expression caused by acupuncture.Ten male New Zealand White rabbits were enrolled in this study. The following acupoints around the left eye, Extra 1 (Taiyang), BL 2 (Zanzhu) and SJ 23 (Sizhukong), were selected for acupuncture therapy. Each rabbit received 10 acupuncture sessions of 30 min, three times per week. A quantity of 50 μl rabbit tear was collected at the pre- and post-acupuncture stage in every subject, respectively. Total protein content analysis, one-dimensional gel electrophoresis and quantitative proteomics analysis (iTRAQ) were performed and the results were compared.Generally, the tear protein expression after acupuncture was different from that before acupuncture though to some extent they were similar. The time spent collecting rabbit tear after acupuncture was shorter than that before acupuncture. The total protein content in rabbit tear pre- and post-acupuncture was 7.12 μg/μl versus 11.28 μg/μl, respectively. One-dimensional gel electrophoresis showed that tear proteins collected before acupuncture were substantially different than post-acupuncture proteins. In total, twenty-eight tear proteins were identified by iTRAQ. Associated with acupuncture were six up-regulated proteins (tear lipocalin, α-1-antiproteinase, histidine-rich glycoprotein, hemopexin, Vitamin D-binding protein, α-2-HS-glycoprotein) and five down-regulated proteins (Annexin A1, serum amyloid A-3 protein, Helicase-like transcription factor, 15 kDa protein A, protein S100-A9).The rabbit tear protein expression difference caused by acupuncture indicates that acupuncture not only stimulates lacrimal gland secretion function but also induces the quantitative change of some proteins in rabbit tear, which may support a positive effect of acupuncture in the treatment of dry eye.

Regulator of G-protein signaling (RGS) proteins 2 (RGS2) and 4 (RGS4) play an important role in regulating G(i/o)- and G(q)-coupled receptors. In the present study, we investigated the possible impact of RGS2 and RGS4 on modulation of glycine currents of rat retinal ganglion cells (RGCs) mediated by the G(i/o)-coupled melatonin MT(2) receptor, using immunohistochemistry, Western blot analysis and whole-cell patch-clamp techniques. By immunofluorescence labeling the expression profiles of RGS2 and RGS4 proteins were basically similar. Both of them were widely expressed in the rat retina, particularly in the inner plexiform layer (IPL) and the ganglion cell layer (GCL). In addition, sparse signals of RGS2 and RGS4 were also detected in the inner nuclear layer (INL). Double immunofluorescence labeling further showed that all of RGCs retrogradely labeled expressed both RGS2 and RGS4. Western blot analysis confirmed the presence of RGS2 and RGS4 proteins in the rat retina. Intracellular dialysis of RGCs with the antibody against RGS2/RGS4 to block RGS2/RGS4 function gradually increased glycine current amplitudes of these cells. In the presence of the RGS2/RGS4 antibody melatonin-induced potentiation of glycine currents of RGCs was not observable. These results suggest that RGS2/RGS4 are coupled to melatonin receptor signaling in rat RGCs and these proteins may regulate the MT(2) receptor to change melatonin-induced modulation of glycine currents in rat RGCs.

Equilibrium and non-equilibrium molecular dynamics and Monte Carlo simulation techniques were applied to predict various thermodynamic, transport and vapor–liquid equilibrium properties of binary mixtures of ethylene glycol and water (EG–W) based on OPLS-AA and SPC/E force fields. The properties predicted include density, vaporization enthalpy, enthalpy of mixing, heat capacities, diffusion coefficients, shear viscosities, thermal conductivities, vapor–liquid coexistence isotherms and isobaric curves, and saturation vapor pressures. Good agreements with experimental data were obtained for most of these properties. Errors are mostly related to inaccuracy found in predictions of pure fluids; a correction to prediction of pure substance can systematically improve prediction for the mixture. This work suggests that OPLS-AA and SPC/E force fields using the common combining rules are transferable for predicting multiple physical properties of EG–W mixtures.

This study aimed to determine whether patients with dry eye syndrome [DES] have more symptoms of anxiety and depression than controls without DES.In this case-control study, the sample consisted of 89 DES subjects (13 diagnosed with Sjögren's syndrome [SS]) and 73 control subjects. Each subject was diagnosed as having DES or was chosen as a control subject by an ophthalmologist. The Zung Self Rating Anxiety Scales (SAS), Zung Self Rating Depression Scales (SDS), and Ocular Surface Disease Index (OSDI) were administered to all subjects. Scores of SAS and SDS, measuring level of anxiety and depression symptoms, were compared between the DES group and the control group. Correlations with other health status measures were conducted.The SAS and SDS scores of the DES group were significantly higher than the control group (P 0.001, P 0.001). The prevalence of DES subjects with anxiety or depression symptoms was significantly higher than in the control group (P = 0.003, P 0.001). In the DES group, SAS scores were found to be correlated with OSDI and educational level. SDS scores were found to be correlated with OSDI. Neither SAS nor SDS scores were correlated with age, sex, household income, tear break up time (BUT), Schirmer Test 1 (S1T), corneal fluorescein staining (FL), or visual acuity.Anxiety and depression are correlated with DES, demonstrating that DES is an important public health problem that merits increased attention and research.

A classical force field capable for accurately predicting surface tensions, surface concentration, and other interfacial properties is reported for sodium dodecyl sulfate (SDS). This force field is proposed by combining parameters from well established force fields for components of the air/SDS/water interface and optimized by adjusting the van der Waals diameter of sulfate oxygen to fit experimental data of surface tension. The force field parameters are transferable; as good agreement with experimental data is achieved from independent calculations on activity derivatives of aqueous solution of sodium methyl sulfate using the Kirkwood-Buff theory. The adjusted parameter effectively modulates the electrostatic interactions of solvated ions in solutions. This modification has a strong impact to surface tension and location and mobility of sodium cations but minimal impact to properties such as density profiles of bulk phase and conformations and orientations of surfactant chain, for which consistent results compared with previous studies are obtained.

We propose to incorporate a lithium tetrazolide group into porous materials for enhancing hydrogen storage capacity. The lithium tetrazolide group is much more stable and polarized than the models made by doping aromatic groups with lithium atoms. More importantly, each of the lithium tetrazolide provides 14 binding sites for hydrogen molecules with modest interaction energies. The advantage of multiple binding sites with modest binding energies is partially demonstrated by constructing a new porous aromatics framework (PAF-4) with the lithium tetrazolide moieties and predicting its hydrogen uptake using first-principles GCMC simulations. The predicted hydrogen uptake reaches 4.9 wt % at 233 K and 10 MPa, which exceeds the 2010 DOE target of 4.5 wt %.

Two-layer ONIOM calculations were carried out to study initial reactions of catalytic cracking of 1-butene to produce propene and ethene on HZSM-5 and HFAU zeolites. Direct cracking and dimerization cracking mechanisms were evaluated. The calculated data indicate that the dimerization cracking is more favorable than the direct cracking based on both kinetic and thermodynamic considerations. HZSM-5 is catalytically more effective than HFAU for the cracking reactions. ONIOM energy analysis shows that the effectiveness of zeolite is due to long-range van der Waals interaction energies that stabilize all reaction intermediates, and short-range interaction between the zeolite and the reacting species that reduce the activation energies. For the dimerization process, stepwise and concerted mechanisms are similar in energy changes. Generally speaking, dimerizations appear to be exothermic reactions with modest activation energies. The activation energies for isomerization, β-scission, and deprotonation are lower...

Enthalpy of mixing (EOM) is one of the most basic thermodynamic properties of mixtures. To assess feasibility of predicting EOM using force field simulation methods, fifteen (15) representative binary mixtures were investigated using MD simulations based on OPLS and TIP4P force fields. The simulation conditions and errors were carefully examined. The precision level of 0.04 kJ/mol was obtained for calculated EOM data. However, the predictions, measured by deviations from experimental data, were only qualitatively correct. Among various factors influencing the accuracy of predictions, force field quality representing interactions among different molecules plays the most significant role. Using methanol/benzene and ethanol/benzene as examples, we demonstrated that non-additive interaction terms between polarizable atoms can be used to significantly improve the quality of predictions. In addition, it appears that charge-dependent LJ parameters are required in order to represent the polarization effects accurately.

This study observes changes in symptoms of xerophthalmia pre- and post-acupuncture therapy and compares the results of the acupuncture therapy (AT) group and the artificial tear control (ATC) group. Parallel comparative studies were carried out on 44 patients with xerophthalmia, who were divided into the AT group (n = 20) and the ATC group (n = 24). A 10-session acupuncture therapy program was performed for the AT group while Dextran 70 was used for the ATC group with each course of treatment lasting 21 day. Examinations were made on the day when a patient was chosen to join the study, 1 hour after completion of treatment, and 3 weeks after stopping treatment. There was no statistically significant difference in terms of the reduction of the symptoms and sign score (SSS) 1 hour after completion of treatment between the AT group and the ATC group. Three weeks after completion of treatment, the reduction of SSS for the AT group was larger than that of the ATC group, with the difference achieving statistical significance. Both acupuncture therapy and artificial tear therapy have an immediate positive effect on the symptoms of xerophthalmia, but acupuncture therapy has a longer continuous effect than that of artificial tears.

An ab initio force field that describes interactions between hydrogen molecules and IRMOF materials is proposed. The force field parameters were derived by fitting to ab initio data that includes higher-order electron correction and extended basis-set effects and validated by calculating adsorption isotherms and isosteric heats of adsorption of H2 in IRMOF-1 using GCMC simulations performed at 77 and 298 K, in a broad range of pressure from 0.0 to 8.0 MPa. Excellent agreements with experimental data were obtained. The force field was then applied to predict hydrogen-storage capacities for eight additional IRMOF materials. It was identified that the void fraction of volume (VFV) has a strong impact on the adsorption capacity, and its impacts on gravimetric and volumetric adsorption uptakes exhibit opposite trends. An overall optimal VFV is ca. 87% for IRMOFs at 77 K and 8.0 MPa.

The octanol–water partition coefficients (Ko/w) and infinite-dilution activity coefficients (γ∞) of 1-ethylpropylamine and 3-methyl-1-pentanol were predicted based on free energy calculations. The multi-configuration thermodynamic integration (TI) method was applied with molecular dynamics simulations to calculate free energy changes. With optimized simulation options and force field parameters the calculated free energy changes were highly precise (uncertainties

This review considers the critical role of the conjunctiva in determining the success or failure of glaucoma filtration surgery. Glaucoma filtration surgery can be defined as an attempt to lower intraocular pressure (IOP) by the surgical formation of an artificial drainage pathway from the anterior chamber to the subconjunctival space. Many types of glaucoma filtration surgery have been developed since the first attempts almost 180 years ago. The wide range of new techniques and devices currently under investigation is testament to the limitations of current techniques and the need for improved therapeutic outcomes. Whilst great attention has been paid to surgical techniques and devices to create the drainage pathway, relatively little attention has been given to address the question of why drainage from such artificial pathways is often problematic. This is in contrast to normal drainage pathways which last a lifetime. Furthermore, the consequences of potential changes in aqueous humour properties induced by glaucoma filtration surgery have not been sufficiently addressed. The mechanisms by which aqueous fluid is drained from the subconjunctival space after filtration surgery have also received relatively little attention. We propose that factors such as the degree of tissue damage during surgery, the surrounding tissue reaction to any surgical implant, and the degree of disruption of normal aqueous properties, are all factors which influence the successful formation of long term drainage channels from the conjunctiva, and that these channels are the key to successful filtration surgery. In recent years it has been suggested that the rate of fluid drainage from the subconjunctival space is actually the determining factor in the resultant IOP reduction. Improved knowledge of aqueous humour induced changes in such drainage pathways has the potential to significantly improve the surgical management of glaucoma. We describe for the first time a novel type of drainage surgery which attempts to minimise surgical trauma to the overlying conjunctiva. The rationale is that a healthy conjunctiva allows drainage channels to form and less opportunity for inflammation and scar tissue formation which are a frequent cause of failure in glaucoma filtration surgery. Successful drainage over extended periods of time has been demonstrated in monkey and rabbit eyes. Long lasting drainage pathways were clearly associated with the presence of lymphatic drainage pathways. A new philosophy in glaucoma drainage surgery is proposed in which minimisation of surgical trauma to the conjunctiva and the encouragement of the development of conjunctival drainage pathways, particularly lymphatic pathways, are central pillars to a successful outcome in glaucoma filtration surgery.

Temperature-programmed desorption curves for ammonia (NH3-TPD) were predicted successfully using grand canonical ensemble Monte Carlo simulation methods and force field parameters derived from quantum mechanical ab initio data. This approach provides a means to study the relationship between the structure and acidity of zeolites at the molecular level. Analysis of the predicted NH3-TPD curves reveals that zeolite pore size is a critical factor influencing the curve shape. The so-called weak and strong acids of zeolites, which give rise to two peaks in the TPD curve, are roughly related to the interactions among ammonia molecules in the pores and to the interactions between ammonia molecules and the zeolite pore walls, respectively. However, the NH3-TPD curves may still show a double peak feature without any strong acid centers if the pore is such a size that additional strain is put on the NH3 hydrogen-bond network.

An all-atom force field for ammonium perchlorate (AP) is developed with the framework of pcff force field. The structural parameters of AP obtained with the modified force field are in good agreement with experimental values. Molecular dynamics (MD) simulations have been performed to investigate AP/HMX (1,3,5,7-tetranitro-1,3,5,7-tetrazocane) composite at different temperatures. The binding energies, thermal expansion coefficient, and the trigger bond lengths of HMX in the AP/HMX composite have been obtained. The binding energies of the system increase slightly with temperature increasing, peak at 245 K, and then gradually decrease. The volume thermal expansion coefficient of the AP/HMX composite has been derived from the volume variation with temperature. As the temperature rises, the maximal lengths of the trigger bond N–NO2 of HMX increase gradually. The simulated results indicate that the maximal length of trigger bond can be used as a criterion for judging the sensitivity of energetic composite.

Density functional theory was employed to study the hydrothermal stability of P-modified ZSM-5 zeolites using cluster models. The calculations of hydrolysis energies indicated that the introduction of phosphorus increases the hydrothermal stability of ZSM-5 zeolites. The initial paths of dealumination were studied with explicit water molecules. It was found that the framework Al-O coordination bond can be replaced by coodination bonds between water molecules and the aluminium. One to three water molecules can form coordination bonds with framework Al and release energies. The P-modification restrain the dealumination. The calculated 27Al NMR chemical shifts for the obtained structures are consistent with the experimental measurements.

A theoretical calculation of the ground and first excited states of two 7-phenylamino-substituted coumarin compounds are performed. In order to study the effect of phenyl substituted in amino group and fluorine atoms substituted in methyl group, 7-amino-4-methyl coumarin (C120) and 7-amino-4-(trifluoromethyl) coumarin (C151) were also studied. The geometries of the ground state and the first ground state were optimized using density function theory and configuration interaction singles levels of theory. Molecular orbitals (MO) of the ground and first excited states of the four coumarin compounds were obtained to explain the change of the structures. ZINDO and TD-DFT methods with different basis sets were applied to predict the UV absorption spectra. The solvent effect had also been taken into account using self-consistent isodensity polarized continuum model. The predicted spectra are in agreement with the experimental data.

Molecular dynamics (MD) and Monte Carlo (MC) methods were applied to calculate thermodynamic properties of ethylene oxide in liquid and vapor phases. The calculations were based on the TEAM force field that was derived based on quantum mechanics data, liquid density and heat of vaporization. Without any modification, the force field was applied to predict various thermodynamic properties including vapor–liquid coexistence curves, critical points, second virial coefficient, isothermal compressibility, surface tensions, shear viscosities and thermal conductivities. Good agreements between the calculated and experimental data are obtained for most properties predicted. Although some of the deviations require further investigation, the force field appears to be transferable for predicting multiple thermodynamic properties.

Computational prediction of adsorption of small molecules in porous materials has great impact on the basic and applied research in chemical engineering and material sciences. In this work, we report an approach based on grand canonical ensemble Monte Carlo (GCMC) simulations and ab initio force fields. We calculated the adsorption curves of ammonia in ZSM-5 zeolite and hydrogen in MOF-5 (a metal-organic-framework material). The predictions agree well with experimental data. Because the predictions are based on the first principle force fields, this approach can be used for the adsorption prediction of new molecules or materials without experimental data as guidance.

The self-organization of large-scale uniform aligned three-dimensional GaN nanoislands with triangular (0001) and distinct sidewall faceting has been realized by metal organic vapor-phase epitaxy on in situ Si-rich SiNx nanoislands patterned c-sapphire substrates. We find that the GaN island shaping is closely related to the SiNx pretreatment chemistry. It is suggested that enhanced surface Ga surfactant effects and compressive strain relaxation caused by site exchanges between excess Si and subsurface Ga atoms are responsible for the distinct triangular island shaping with large lateral size, smooth sidewall facets, and sharp triangle corners. Photoluminescence studies also show Si-doping-induced compressive strain relaxation and improved crystalline qualities for triangular GaN islands grown with the Si-rich SiNx pretreatment.

The periodic perturbation method is applied to predict shear viscosities of liquid 1,4-butanediol, 1,3-butanediol, 1,2-butanediol, 2-methyl-1,3-propanediol and 1,2,4-butanetriol under two thermodynamical conditions: T = 373 K, P = 0.1 MPa and T = 373 K, P = 250 MPa. A linear dependence of the calculated shear viscosities with respect to the applied perturbation forces is identified. Based on this finding, extrapolation of the calculated viscosities to zero perturbation force is applied to estimate the shear viscosities for the “undisturbed” fluids. The uncertainties of the estimates are calculated using the block average method. The predicted values compare favorably with the experimental data. Although the force field is optimized using equilibrium properties (liquid densities and vaporization enthalpies), calculated results demonstrate that the force field can be used to predict the kinetic properties accurately. The force field parameters are well transferable among different state points. However, transferring parameters among different molecules should be executed with caution.

A semi-ionic model is proposed for simulations of bulk metal oxides and interfaces between metal oxides and organic molecules. In this model, the electrostatic interactions are represented by partial charges on atoms; the covalent contributions are represented by a Morse function, and the van der Waals interactions are represented by a Lennard-Jones (LJ) function. Four potential functions are parametrized, using experimental data of representative binary oxides, by combining the Morse and electrostatic terms with LJ-12-6, LJ-9-6, and polarization shell model. The resulting potential functions are validated by predicting bulk properties of binary and ternary oxides. Coupled with classical force field parameters for organic molecules, one of the potentials is applied to study the adsorption energies, structures, and isothermal curves of methanol molecules on a MgO (100) surface.

BACKGROUND AND OBJECTIVE To measure the concentrations of transforming growth factor-beta1 and beta2 (TGF-beta1 and TGF-beta2) in the aqueous humor of patients with neovascular glaucoma (NVG). PATIENTS AND METHODS Patients were divided into four groups: NVG secondary to central retinal vein occlusion (group 1), NVG secondary to proliferative diabetic retinopathy (group 2), central retinal vein occlusion without rubeosis (group 3), and senile cataract (group 4). The total TGF-beta1 and TGF-beta2 concentrations in the aqueous humor of the four groups were measured by enzyme linked immunosorbent assay. RESULTS The mean concentrations of total TGF-beta1 were 600.7 ± 436.7 µg/mL in group 1, 802.0 ± 359.5 µg/mL in group 2, and undetectable in groups 3 and group 4 (P < .05). The mean concentrations of total TGF-beta2 were 6,307.9 ± 2,206.2 µg/mL in group 1, 5,908.0 ± 2,033.2 µg/mL in group 2, 899.7 ± 425.6 µg/mL in group 3, and 385.7 ± 189.9 µg/mL in group 4. The total TGF-beta1 and TGF-beta2 concentrations in groups 1 and 2 were significantly higher than those in groups 3 and 4, whereas the total TGF-beta2 concentration in group 3 was significantly higher than that in group 4 (P < .05). There was no significant difference in the TGF-beta1 or TGF-beta2 concentrations between groups 1 and 2 (P > .05). CONCLUSIONS The abnormally high concentrations of TGF-beta1 and TGF-beta2 in the aqueous humor of patients with NVG may explain some aspects of the pathogenesis of NVG and the high failure rate of filtering operations in NVG. [Ophthalmic Surg Lasers Imaging 2007;38:6-14.] AUTHORS From the Department of Ophthalmology (X-BY, X-HS, W-YG, S-HQ, F-RM, Y-LS), Shanghai Eye and ENT Hospital, Fudan University, Shanghai, People’s Republic of China; the Department of Ophthalmology (ED), University of the Witwatersrand, Johannesburg, South Africa; and The Royal Victorian Eye & Ear Hospital (GJBS), East Melbourne, Victoria, Australia. Accepted for publication June 14, 2006. Supported by research grants (No. Z23) from Shanghai Eye and ENT Hospital, Fudan University, Shanghai, People’s Republic of China. Address correspondence to Xing-Huai Sun, MD, PhD, Department of Ophthalmology, Shanghai Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 20031, People’s Republic of China.

Whether or not a coarse grained force field (CGFF) can be made to be transferrable is an important question to be addressed. By comparing potential energy with potential of mean force (PMF) of a molecular dimer, we proposed to use a free energy function (FE-12-6) with the parameters in entropic and energetic terms explicitly to represent the nonbond interactions in CGFF. Although the FE-12-6 function cannot accurately describe the PMF curves, a cancelation of short radii and strong repulsion makes the function a good approximation. For nonpolar molecules represented by linear alkanes, FE-12-6 is demonstrated to be highly effective in representing the nonbond interactions in CGFF. The force field parameters are well transferrable among different alkane molecules, in different thermodynamic states and for predicting various thermodynamic properties including heats of vaporization, vapor-liquid-equilibrium coexistence curves, surface tensions, and liquid densities.

The COMPASS II force field has been developed by extending the coverage of the COMPASS force field (J Phys Chem B 102(38):7338–7364, 1998) to polymer and drug-like molecules found in popular databases. Using a fragmentation method to systematically construct small molecules that exhibit key functional groups found in these databases, parameters applicable to database compounds were efficiently obtained. Based on the same parameterization paradigm as used in the development of the COMPASS force field, new parameters were derived by a combination of fits to quantum mechanical data for valence parameters and experimental liquid and crystal data for nonbond parameters. To preserve the quality of the original COMPASS parameters, a quality assurance suite was used and updated to ensure that additional atom-types and parameters do not interfere with the existing ones. Validation against molecular properties, liquid and crystal densities, and enthalpies, demonstrates that the quality of COMPASS is preserved and the same quality of prediction is achieved for the additional coverage.

In the synthesis of zeolites and related crystalline materials with open-frameworks, a single structure is obtained in the presence of many different templates, known as the “one-structure/multiple-templates” phenomenon. However, the reasons behind this phenomenon have yet to be elucidated. By analyzing the possible starting point of crystallization in several “one-structure/multiple-templates” systems and applying the molecular dynamics simulation to such systems, we found that the template-framework binding free energy level or charge transfer (exchange) degree was the key to the structure-directing effect of a template. This discovery explains why the structure-directing effect of a template can be affected by many variables, such as the nature of the source materials, molar composition of the initial reaction mixture (recipe), mineralizers, type of solvent and heating temperature. In the synthesis of zeolites and related crystalline materials with open-frameworks, the template or organic additive played a topological structure-directing role instead of a structure-directing role.

Molecular simulation is a promising tool for the study of zeolite formation. However, sufficient sampling remains a grand challenge for the practical use of molecular simulation for this purpose. Here, we investigate the initial stage of zeolite synthesis under realistic conditions by using the replica-exchange method and the ReaxFF reactive force field. After a total simulation time of 480 ns, both energetic and structural properties approach convergence. Analyses of data collected at 600 K show that the inorganic structure directing agent NaOH promotes the aggregation of silicate, the formation of branched Si atoms and the formation of 5-membered rings. With the trajectories collected simultaneously at different temperatures, the effect of temperature is discussed.

Recently we reported studies of the iris microvasculature and its endothelial cells using intra-luminal micro-perfusion, fixation, and silver staining, suggesting that the iris vascular endothelium may be crucial for maintaining homeostasis in the ocular anterior segment. Here we present information regarding the intracellular structure and cell junctions of the iris endothelium. Thirty-seven porcine eyes were used for this study. The temporal long posterior ciliary artery was cannulated to assess the iris microvascular network and its endothelium using intra-luminal micro-perfusion, fixation, and staining with phalloidin for intracellular cytoskeleton f-actin, and with antibodies against claudin-5 and VE-cadherin for junction proteins. Nuclei were counterstained with Hoechst. The iris was flat-mounted for confocal imaging. The iris microvasculature was studied for its distribution, branch orders and endothelial morphometrics with endothelial cell length measured for each vessel order. Our results showed that morphometrics of the iris microvasculature was comparable with our previous silver staining. Abundant stress fibres and peripheral border staining were seen within the endothelial cells in larger arteries. An obvious decrease in cytoplasmic stress fibres was evident further downstream in the smaller arterioles, and they tended to be absent from capillaries and veins. Endothelial intercellular junctions throughout the iris vasculature were VE-cadherin and claudin-5 immuno-positive, indicating the presence of both adherent junctions and tight junctions between vascular endothelial cells throughout the iris microvasculature. Unevenness of claudin-5 staining was noted along the endothelial cell borders in almost every order of vessels, especially in veins and small arterioles. Our results suggest that significant heterogeneity of intracellular structure and junction proteins is present in different orders of the iris vasculature in addition to vascular diameter and shape of the endothelia. Detailed information of the topography and intracellular structure and junction proteins of the endothelium of the iris microvasculature combined with unique structural features of the iris may help us to further understand the physiological and pathogenic roles of the iris vasculature in relevant ocular diseases.

A gemini type of supramolecular amphiphile with a double ion-pair structure was fabricated through proton-transfer hydrogen bonding. In dioxane, the complexes could self-assemble into reverse micelles and vesicles.

Isothermal–isobaric ensemble (NPT) molecular dynamics (MD) simulation was applied to calculate the heats of mixing for binary fluids based on an all-atom force field. The calculation protocol was tested on mixtures of 1-propanol/ n -heptane, n -butylamine/ n -heptane and n -butylamine/water at various temperatures and compositions. Based on a simple error analysis and comparisons of calculated and experimental data, we propose that a necessary but not sufficient condition in the predictions of the heats of mixing is to have a force field highly accurate in evaluating energetic properties for pure substances. More work is required in order to find out the sufficient conditions.

Widom insertion method coupled with canonical ensemble (NVT) molecular simulations based on different force fields was utilized to calculate Henry's law constants (HLCs) of several common gas molecules, N 2 , O 2 , CH 4 , and CO 2 , in liquid ethylene oxide and ethanol. Several simulation options, including insertion grid densities, liquid densities, force field models, and simulation methods were investigated. The results indicate that reasonably good agreements between the calculated and experimental values were obtained using the united-atom (UA) model. However, systematically overestimated values are obtained with the all-atom (AA) force field model. The causes of the problems were investigated comparatively. The data indicate that hydrogen atoms in the AA model are mainly responsible for these problems, but the underlying sampling algorithm in Widom insertions, which may be the real source of problems, needs further investigation.

Ab initio methods were used to investigate the α-fluorination of simple phosphonic acid molecules. We found that fluorine atoms are not strong hydrogen bond acceptors, and the substitution marginally enhances the hydrogen bonds between the phosphonic group (–PO(OH) 2 ) and its surrounding polar groups. However, profound effects are observed in the stability of ionic species due to the substitution of fluorine atom(s). The proton transfer from phosphonic acids to proton-accepting groups such as water or ammonia molecules is energetically plausible in water solution to generate anions, and the α-fluorination significantly stabilizes the anions. This result explains the established correlation between bioactivities and the p K a values and sheds light on the significant enhancement in the bioactivity of phosphatase inhibitors due to their fluoro-substitution.

Automatic parameterization procedures, which are important components in our latest approach of making transferable and extensible general force fields, were demonstrated by deriving parameters from ab initio and empirical data, and subsequently predicting densities for nine molecular fluids. Excellent agreements with available experimental data were obtained for most of the systems studied. The automated procedure for deriving van der Waals parameters, constructed by combining the molecular dynamics simulation and statistical mechanical perturbation theory, is described.

Ab initio molecular dynamics simulations were conducted to study the thermal decomposition mechanisms of solid FOX-7. We found that the initial decomposition of FOX-7 has three main reaction routes. The C–NO2 bond fission as reported previously is indeed the most common route. However, the inter- and intramolecular hydrogen transfers are also found to be valid, which is contradictory to previous energy minimization calculation results. The simulations agree well with known experimental data in terms of activation energy and reaction side products. A complete reaction network that describes how the main products, H2O, CO2 and N2 form in FOX-7 decomposition, is constructed from the simulation trajectories.

One of the challenges in material science has been to prepare macro- or mesoporous zeolite. Although examples of their synthesis exist, there is a need for a facile yet versatile approach to such hierarchical structures. Here we report a concept for designing a single quaternary ammonium head amphiphilic template with strong ordered self-assembling ability through π-π stacking in hydrophobic side, which stabilizes the mesostructure to form single-crystalline mesostructured zeolite nanosheets. The concept is demonstrated for the formation of a new type of MFI (zeolite framework code by International Zeolite Association) nanosheets joined with a 90° rotational boundary, which results in a mesoporous zeolite with highly specific surface area even after calcination. Low binding energies for this self-assembling system are supported by a theoretical analysis. A geometrical matching between the arrangement of aromatic groups and the zeolitic framework is speculated for the formation of single-crystalline MFI nanosheets.

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs.

As a part of the COMPASS force field development, a number of small inorganic molecules were parametrized for condensed-phase applications. Using a simple valence model coupled with Coulomb energy and Lennard-Jones 9−6 functional terms, the parameters were optimized to yield accurate prediction of structural, vibrational, and thermophysical properties for these molecules. Extended validation on liquid nitrogen (N2) and carbon dioxide (CO2) in normal and supercritical conditions demonstrates that the present force field is capable of predicting various thermophysical properties in a very broad range of experimental conditions.

To investigate the mechanical and other condensed phase properties of energetic materials using atomistic simulation techniques, the COMPASS force field has been expanded to include high-energy nitro functional groups. In this paper, the parameterization and validation of COMPASS for nitrate esters (−ONO2) is presented. The functional forms of this force field are of the consistent force field type. The parameters were derived with an emphasis on the nonbonded parameters, which include a Lennard-Jones 9−6 function for the van der Waals (vdW) term and a Coulombic term for an electrostatic interaction. To validate the force field, molecular mechanics calculations and molecular dynamics simulations have been made on a variety of molecules containing the nitrate ester functionality. Excellent agreement has been obtained between the calculated and experimental values for molecular structures, vibrational frequencies, liquid densities, heats of vaporization, crystal structure, mechanical properties, and lattice...