Test of the Inverse Monte Carlo Method for the Calculation of Interatomic Potential Energies in Atomic Liquids

Abstract

The principle purpose of this paper is to demonstrate the use of the Inverse Monte Carlo technique for calculating pair interaction energies in monoatomic liquids from a given equilibrium property. This method is based on the mathematical relation between transition probability and pair potential given by the fundamental equation of the “importance sampling” Monte Carlo method. In order to have well defined conditions for the test of the Inverse Monte Carlo method a Metropolis Monte Carlo simulation of a Lennard Jones liquid is carried out to give the equilibrium pair correlation function determined by the assumed potential. Because an equilibrium configuration is prerequisite for an Inverse Monte Carlo simulation a model system is generated reproducing the pair correlation function, which has been calculated by the Metropolis Monte Carlo simulation and therefore representing the system in thermal equilibrium. This configuration is used to simulate virtual atom displacements. The resulting changes in atom distribution for each single simulation step are inserted in a set of non-linear equations defining the transition probability for the virtual change of configuration. The solution of the set of equations for pair interaction energies yields the Lennard Jones potential by which the equilibrium configuration has been determined.     

Simulations on the Primitive Electrolyte Environment of a High Charge-density Polyelectrolyte. A Sampling Problem and its Solution

Abstract

We show that the classical Metropolis Monte Carlo (MMC) algorithm converges very slowly when applied to the primitive electrolyte environment for a high charge-density polyelectrolyte. This slowness of convergence, which is due to the large density inhomogeneity around the polyelectrolyte, produces noticeable errors in the ion distribution functions for MMC runs of 1.3 × 10⁶ trial steps started from nonequilibrium distributions. We report that an algorithm which we call DSMC (for density-scaled Monte Carlo) overcomes this problem and provides relatively rapid convergence in this application. We suggest that DSMC should be well-suited for other Monte Carlo simulations on physical systems where large density inhomogeneities occur.     

Redescription of Echinostoma trivolvis (Cort, 1914) (Trematoda: Echinostomatidae) with a discussion on its identity

The life-cycle of Echinostoma trivolvis (Cort, 1914) has been completed experimentally and the validity and identity of this species are discussed. Synonyms for cercariae and adults of E. trivolvis are as follows: Cercaria trivolvis Cort, 1914, C. trisolenata Faust, 1917, C. acanthostoma Faust, 1918, C. complexa Faust, 1919; Distoma echinatum Zeder, 1803, of Leidy (1888, 1904) and Hassall (1896); E. echinatum (Zeder, 1803) of Hassall (1896), Stiles & Hassall (1895), Barker & Laughlin (1911), Barker (1916) and Swales (1933); E. revolutum (Frölich, 1802) Dietz, 1909 of Johnson (1920), Fallis (1934), Beaver (1937) and Fried & co-workers (1968–1989); E. armigerum Barker & Irvine, 1915; E. coalitum Barker & Beaver, 1915; E. callawayensis Barker & Noll, 1915; E. paraulum Dietz, 1909 of Miller (1937); E. multispinosum Vigueras, 1944; and Echinoparyphium contiguum Barker & Bastron, 1915. The first intermediate host is the planorbid snail Helisoma trivolvis. Second intermediate hosts are various pulmonate and prosobranch snails, mussels, planarians, fishes, frogs, tadpoles and freshwater turtles. Final hosts are various birds and mammals. E. trivolvis occurs only in North America.     

Simulation methods for protein structure fluctuations

Three numerical techniques for generating thermally accessible configurations of globular proteins are considered; these techniques are the molecular dynamics method, the Metropolis Monte Carlo method, and a modified Monte Carlo method which takes account of the forces acting on the protein atoms. The molecular dynamics method is shown to be more efficient than either of the Monte Carlo methods. Because it may be necessary to use Monte Carlo methods in certain important types of sampling problems, the behavior of these methods is examined in some detail. It is found that an acceptance ratio close to 1/6 yields optimum efficiency for the Metropolis method, in contrast to what is often assumed. This result, together with the overall inefficiency of the Monte Carlo methods, appears to arise from the anisotropic forces acting on the protein atoms due to their covalent bonding. Possible ways of improving the Monte Carlo methods are suggested.     

Networks of Water Molecules in a Proflavine Deoxydinucleoside Phosphate Complex

Abstract

Using previously reported ab-initio atom-atom potentials for the interactions of a water molecule with phosphates, sugars and bases and newly computed ab-initio atom-atom potentials for the interaction between a proflavine ion and water, we have analyzed with the Monte-Carlo Metropolis method networks of water molecules hydrating a 2:2 complex of proflavine and deoxycytidylyl-3′,5′-guanosine, recently studied with X-ray crystallography. From our simulations we have i) verified the quality of our atom-atom potentials by obtaining patterns of oxygen atoms in very good agreement with the X-ray patterns for the minor groove and in reasonable agreement in the major groove, ii) predicted the water's hydrogen atoms positions and iii) preliminarily predicted the number of water molecules not reported in the X-ray study but present in the major groove. The above data, even if preliminary, and the analyses on the energetics of the water-water, water-proflavine and water-dCpG interactions indicate that very detailed accounts on the water filaments in the above crystal can be obtained optimally by merging computer and X-ray experiments.     

Identification of a novel species of Eimeria Schneider, 1875 from the woylie,Bettongia penicillata Gray (Diprotodontia: Potoroidae) and the genetic characterisation of three Eimeria spp. from other potoroid marsupials

Faecal samples (n = 1,093) collected from the woylie Bettongia penicillata Gray, in south-western Australia were examined for the presence of coccidian parasites. Eimeria sp. oöcysts were detected in 15.2% of samples. Faecal samples obtained from the eastern bettong Bettongia gaimardi (Desmarest) (n = 4) and long-nosed potoroo Potorous tridactylus (Kerr) (n = 12) in Tasmania, were also screened for the presence of Eimeria spp. (prevalence 50% and 41.7%, respectively). Morphological and genetic comparison with other known species of Eimeria indicates that the material identified in woylies is novel. This study aimed to (i) morphologically describe and genetically characterise Eimeria woyliei n. sp. found in woylies; and (ii) genetically characterise Eimeria gaimardi Barker, O’Callaghan & Beveridge, 1988, Eimeria potoroi Barker, O’Callaghan & Beveridge, 1988, and Eimeria mundayi Barker, O’Callaghan & Beveridge, 1988, from other potoroid marsupials. Molecular phylogenetic analyses conducted at the 18S rDNA and mitochondrial cytochrome c oxidase subunit 1 (cox1) loci revealed that E. woyliei n. sp. was most closely related to Eimeria setonicis Barker, O’Callaghan & Beveridge, 1988, at the 18S rDNA locus, and Eimeria trichosuri O’Callaghan & O’Donoghue, 2001, at the cox1 locus. Eimeria woyliei n. sp. is the sixth species of Eimeria to be formally described from potoroid marsupials.

     

Conformational analysis of α-d-Fuc-(1→4)-β-d-GlcNAc-OMe. One-dimensional transient NOE experiments and metropolis Monte Carlo simulations

Summary One-dimensional transient NOE build-up curves were measured for the synthetic disaccharide -d-Fuc-(14)--d-GlcNAc 1 utilizing Gaussian shaped pulses. Simulated build-up curves from Metropolis Monte Carlo simulations were compared to the experimental data. Disaccharide 1 is structurally related to methyl -d-maltoside in that it also contains an -(14) linkage, and it has the same configuration of groups around the glycosidic linkage. Analysis of NOEs in methyl -d-maltoside is restricted to those observed upon selective excitation of H1 because of severe spectral overlap. The situation is different in 1 where ¹H-NMR signals are well separated. Several interglycosidic NOEs were observed. The corresponding build-up curves allowed an accurate determination of the conformational preferences at the glycosidic linkage in 1. Comparison of experimental and theoretical NOE build-up curves showed clearly that rigid minimum-energy models cannot account for the experimental data. The best fit of experimental NOE build-up curves was obtained with theoretical curves from a 2×10⁶ step Metropolis Monte Carlo simulation with the temperature parameter set at 1000 K. Finally, it was observed that only the interglycosidic NOE H5/H6-pro-S significantly depends upon varying conformation distributions at the -(14)-glycosidic linkage, induced by choosing different temperature parameters for the Metropolis Monte Carlo simulations.     

A new species,new host records and life cycle data for lepocreadiids (Digenea) of pomacentrid fishes from the Great Barrier Reef,Australia

A new species of lepocreadiid, Opechonoides opisthoporus n. sp., is described infecting 12 pomacentrid fish species from the Great Barrier Reef, Australia, with Abudefduf whitleyi Allen & Robertson as the type-host. This taxon differs from the only other known member of the genus, Opechonoides gure Yamaguti, 1940, in the sucker width ratio, cirrus-sac length, position of the testes, position of the pore of Laurer’s canal, and relative post-testicular distance. The new species exhibits stenoxenic host-specificity, infecting pomacentrids from seven genera: Abudefduf Forsskål, Amphiprion Bloch & Schneider, Neoglyphidodon Allen, Neopomacentrus Allen, Plectroglyphidodon Fowler & Ball, Pomacentrus Lacépède and Stegastes Jenyns. Phylogenetic analyses of 28S rDNA sequence data demonstrate that O. opisthoporus n. sp. forms a strongly supported clade with Prodistomum orientale (Layman, 1930) Bray & Gibson, 1990. The life cycle of this new species is partly elucidated on the basis of ITS2 rDNA sequence data; intermediate hosts are shown to be three species of Ctenophora. New host records and molecular data are reported for Lepocreadium oyabitcha Machida, 1984 and Lepotrema amblyglyphidodonis Bray, Cutmore & Cribb, 2018, and new molecular data are provided for Lepotrema acanthochromidis Bray, Cutmore & Cribb, 2018 and Lepotrema adlardi (Bray, Cribb & Barker, 1993) Bray & Cribb, 1996. Novel cox1 mtDNA sequence data showed intraspecific geographical structuring between Heron Island and Lizard Island for L. acanthochromidis but not for L. adlardi or O. opisthoporus n. sp.

     

Assessment of the frost sensitivity of Trifolium species by chlorophyll fluorescence analysis

The potential of the chlorophyll fluorescence technique in screening for frost sensitivity in a range of Trifolium species from different geographical origins was assessed by measuring the decrease in variable chlorophyll fluorescence (F_var) of leaves after freezing at - 5°C for 60 min. The method was rapid and the results obtained agreed well with a visual assessment of freezing injury carried out after leaves were returned to optimal growth conditions for 72 h. Trifolium alexandrinum (Berseem clover) cv. Tabor originating from Israel was shown to be the most frost sensitive species studied and Trifolium subterraneum (subterranean clover) cv. Mt. Barker, from temperate regions of Australia, the most frost resistant. On extended periods of freezing, frost damage increased and this was associated with a further reduction in variable chlorophyll fluorescence and in quenching capacity of the thylakoid membranes. These results thus indicate that substantial thylakoid membrane dysfunction is induced at freezing temperatures. Furthermore, it was found that frost hardening of the frost sensitive species T. alexandrinum for 21 days at 5°C reduced the extent of damage sustained by the thylakoid membranes as shown by higher fluorescence quenching capacity, smaller reduction in variable fluorescence (F_var) and higher initial fluorescence (F_o) when leaves of hardened plants were frozen at -5°C and -7°C.     

Leishmania braziliensis:Characterisation of a Complex Specific Subtelomeric Repeat Sequence and Its Use in the Detection of Parasites

Fu, G., Perona-Wright, G., and Barker, D. C. 1998.Leishmania braziliensis: Characterisation of a complex specific subtelomeric repeat sequence and its use in the detection of parasites.Experimental Parasitology90, 236–243. A 1.6-kb tandem repeat sequence had previously been identified in the subtelomeric region of mini- and megabase chromosomes fromLeishmania braziliensis.Southern hybridisation was used to demonstrate that the repeat is complex specific. The sequence was characterised in strains representing four species of theL. braziliensiscomplex. This data allowed an assessment of the evolutionary relationship of the four species. PCR primers targeted to the repeat amplify only DNA from species of theL. braziliensiscomplex. Titration assays indicate that a minimum of 50 fg of parasite DNA can be detected by PCR alone. Southern hybridisation increases the limit of detection to 5 fg. Interspecies variation in the repeat sequence enabled restriction enzyme digestion of PCR products to distinguish individual species within theL. braziliensiscomplex.     

Synthesis of novel carbazole chalcones as radical scavenger,antimicrobial and cancer chemopreventive agents

A series of novel carbazole chalcones has been synthesised and evaluated for radical scavenging activity, cytotoxicity and antimicrobial activities. Compounds 12m, 12o and 12c exhibited good 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, compounds 12e, 12m and 12d were excellent hydroxyl radical scavengers and compounds 12a, 12e, 12g, 12n and 12m have shown inhibition of oxidative DNA damage induced by 2,2′-azobis (2-amidinopropane hydrochloride). Compounds 12j, 12i, 12n, 12c, 12m and 12e were most active against the selected cancer cell lines. Compounds 12a, 12e and 12m showed good antibacterial activity and compounds 12h and 12m have shown good antifungal activity. All the compounds were subjected for absorption, distribution, metabolism and excretion (ADME) predictions by computational method and found that these molecules could be considered as potential candidates for oral drug development.     

Purification of the Neurite Outgrowth Promoting Fragment of Mouse Laminin

Abstract

A method for isolation of the neurite outgrowth promoting fragment of mouse laminin (fragment 8) is described in this paper. Besides producing excellent yields, this method was shown to be fast and practical, since it is based on a single step which consists in an ion exchange chromatography of elastase digested laminin.     

Visual Methodologies

Three Cheers (at least) for Intervention Press! Crawford, Peter Ian, The Nordic Eye. Proceedings from NAFA 1. Aarhus; Intervention Press; 122 pp, 1992.0 US$ 18.50.

Crawford, Peter Ian and Jan K., Simonsen, Ethnographic Film. Aesthetics and Narrative Traditions. Proceedings from NAFA 2. Aarhus; Intervention Press; 251 pp, index, 1992. US$ 29.00.

Scott, Chuck., The Lesotho Video Herders Project: Explorations in Anthropology. Aarhus; Intervention Prees; in association with the Centre for Cultural and Media Studies, University of Natal, Durban. Photographs, maps, appendices, 123 pp, 1994. US$ 16.60. (The book can be ordered along with a 40 minute videotape).

European distributor: Intervention Press, Casternschioldsvej 7, DK‐8270 Højbjerg, Denmark.

North American distributor: Smyrna Press, Box 021803, GPO, Brooklyn, NY 11202, USA.

Lesotho Herders Video Project Chuck Scott, Lesotho Herders Video Project: Explorations in Visual Anthropology. Højbjerg, Denmark: Intervention Press in association with the Center for Cultural and Media Studies, University of Natal, Durban, South Africa, 1994. 123pp., photographs, maps, appendices. (European orders: Intervention Press, ECU 15. North American distributor is Smyrna Press, Box 021803, Brooklyn, NY 11202). US $ 16.60.

The Tiguas Wright, Bill. The Tiguas: Pueblo Indians of Texas. El Paso: Texas Western Press, University of Texas at El Paso, 1993. 161 pp., hdbd., $40.00.

Always Getting Ready Barker, James H. Always Getting Ready Upterrlainarluta: Yup'ik Subsistence in Southwest Alaska. Seattle: University of Washington Press, 1993. 144 pp. Pbk. $ 29.95.     

Infrared-spectral characteristics of some acetylated,anomeric glycosides

Barker and co-workers had described the C-1-H deformation bands in the ranges 844 ±8 cm^?1 and 891 ±7 cm^?1 as characteristic bands for the α and β anomers, respectively, of hexo- and pento-pyranoses and -pyranosides, and their derivatives. Later, Audichya and co-workers reported the presence of the 844 ±8-cm^?1 band for both anomers of some aryl d-glucoside derivatives, making the applicability of the earlier findings doubtful. Examination by us of the i.r. spectra of some aryl glycoside derivatives suggested that the origin of the band at 844 ±8 cm^?1 for the β anomers of the p-substituted-aryl glycoside derivatives studied by Audichya et al. could be a CH, out-of-plane deformation-mode of the substituted aromatic ring. Also, their further claim of a characteristic band in the region 961-957 cm^?1 for α anomers is shown to be of little diagnostic value. The relative intensities of bands in the COC stretching region, 1100-1000 cm^?1, and a band near 300 cm^?1 in the COC deformation region, found only for the β anomers, are shown to be helpful in differentiating the anomers of some peracetylated alkyl and aryl glycosides.     

Automated Synthesis of Cyclic Oligodeoxyribonucleotides via Phosphoramidite Method

Abstract

The functionalized polyethylene glycol/polystyrene copolymer support 4 was shown to be suitable for a completely automated synthesis of small- to medium-sized cyclic oligodeoxy-ribonucleotides. Syntheses of the linear precursors were achieved by the phosphoramidite method, whereas the cyclization reactions were based on the phosphotriester chemistry.     

Biochemical and cytogenetic biomarkers of pollutant exposure in marine fish (Aldrichetta forsteri Valenciennes and Sillago schomburgkii Peters) near industrial and metropolitan centres in South Australia

This project aimed to measure biochemical and cytogenetic biomarkers in marine fish (Aldrichetta forsteri and Sillago schomburgkii) associated with industrial and urban centres in South Australia. These sites were Port Pirie (affected by metal-contaminated outflows), Barker Inlet (adjacent to Metropolitan Adelaide), and Wills Creek (reference site). The biochemical biomarkers included sorbitol dehydrogenase (SDH) and alanine aminotransferase (ALAT) in serum, adenylate levels (ATP, ADP and AMP) and adenylate energy charge (AEC) in gill and liver, and sodium/potassium ATPase (Na⁺, K⁺-ATPase) in gill. Erythrocyte micronucleus frequency was a marker of cytogenetic effect. Serum enzyme levels were generally higher in fish from Port Pirie and Barker Inlet than in those from Wills Creek, with SDH demonstrating the clearest site-associated differences. Tissue adenylates were consistently lower at Port Pirie than elsewhere, suggesting a greater metabolic strain in fish at this site. AEC in gill and liver were consistently lower at Port Pirie than at Wills Creek, with Barker Inlet generally between these two. The reversed rank order was observed with erythrocyte micronucleus frequencies. Seasonal variations in the biomarkers may be attributed either to seasonal physiological changes in fish or changes in pollutant input levels or compositions. Na⁺, K⁺-ATPase did not differ between sites nor seasons in this study. This work shows that biochemical and cytogenetic differences occur in marine fish at specific locations in South Australia. It also shows that of these tests, serum SDH and erythrocyte micronuclei are potentially the most sensitive and reliable biomarkers of pollutants effects on marine fish. The results also suggest that these data may be used as a baseline against which future changes in marine water quality, and their consequent biological effects, can be compared.     

Determination of antibiotic impurities in good manufacturing practices-grade cell therapy medicinal products

Abstract

Backrounds: According to the regulations of the health autorities, cell-based therapy products must be manufactured in good manufacturing production (GMP) facilities, fulfilling the required GMP standards. Products developed under the high quality control (QC) necessarity need to be approved for some QC tests. One of the main residual test is antibiotic test and this test should be validated. The aim of this study is to validate and determine the methods of detection of the antibiotic residue in the final product.

Methods: Liquid Chromatography Tandem-Mass Spectrometry (LC-MS/MS) methods were used for the main steps of the production procedure, as well as the final products. Pharmaceutical Grade penicillin G and streptomycin sulfate were used as positive controls.

Results: The results suggest that penicillin is broken down during cell culture and streptomycin is eliminated at the first washing step of the final product manufacture. It is shown in this study that LC-MS/MS method is one of the convenient method to test residual anibiotics and can be used to detect the antibiotic residues in cellular therapy products.

Discussion: Since the antibiotic residues are eliminated in the final product and also it could be suggested that the methodology we followed is sufficiently safe and final product is pure.     

Transport mechanism of hydroxy-propyl-beta-cyclodextrin modified solid lipid nanoparticles across human epithelial cells for the oral absorption of antileishmanial drugs

BackgroundIn this study, the transport mechanism of fluorescently labeled hydroxypropyl beta-cyclodextrin (HPβ-CD) modified SLNs loaded with Amphotericin B (AmB) and Paromomycin (PM) have been investigated by using in vitro human epithelial cell model of a human colonic adenocarcinoma cell line (Caco-2).MethodsFabrication of HPβ-CD modified fluorescently labeled AmB and PM-loaded SLNs (HP?-CD-FITC-DDSLNs) was performed by using the emulsion solvent evaporation method. Caco-2 cells were used to investigate different endocytosis and exocytosis pathways to be followed by the nanoparticles. Intracellular co-localization of nanoformulation with different organelles was investigated.ResultsThe toxicity studies have shown the biocompatible nature of the modified lipid nanoparticles. The average particle size and PDI of HP?-CD-FITC-DDSLNs were found to be 187 ± 2.3 nm and 0.31 respectively. The most prevalent endocytosis mechanisms were shown to be macropinocytosis and caveolae (lipid raft) dependent pathways. The Golgi complex and endoplasmic reticulum are the confirmed destinations of HP?-CD-FITC-DDSLNs in the Caco-2 cell monolayer, even though lysosomes have been shown to escape and play a minimal role during nanoparticle transport.ConclusionHP?-CD-DDSLNs were found to be biocompatible and safe for delivering hydrophobic as well as hydrophilic drugs through an oral route to target the RES system for the treatment of visceral leishmania.General significanceUnderstanding the process underlying the transport of modified solid lipid nanoparticles for oral drug delivery could be useful for many medicines with low solubility, permeability, and stability.     

Diels–Alder reactivity of benzannulated isobenzofurans as assessed by density functional theory

Density functional theory (DFT) calculations at the B3LYP/6-31G* level for isobenzofuran 1 and eleven benzannulated derivatives of types 2 and 3 have been performed in order to compare their relative reactivities as dienes in Diels–Alder reactions. The transition state (TS) energies for their reactions with ethylene have been determined and shown to form a linear correlation between activation energies and structure count (SC) ratios. TS energies as a method for comparison of diene reactivities can be applied to IBFs bearing substituents on the ring as well as those containing heteroatoms, for which the SC ratio method failed. Different measures of aromaticity of benzannulated IBFs indicated a decrease in aromaticity going from 4 to 14, which is also reflected in their reactivity as a dienes in Diels–Alder reaction. Figure Isobenzofuran 1 and benzannulated isobenzofurans 2 and 3      

CRANKITE: A fast polypeptide backbone conformation sampler

Background

CRANKITE is a suite of programs for simulating backbone conformations of polypeptides and proteins. The core of the suite is an efficient Metropolis Monte Carlo sampler of backbone conformations in continuous three-dimensional space in atomic details.

Methods

In contrast to other programs relying on local Metropolis moves in the space of dihedral angles, our sampler utilizes local crankshaft rotations of rigid peptide bonds in Cartesian space.

Results

The sampler allows fast simulation and analysis of secondary structure formation and conformational changes for proteins of average length.