bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast semiempirical calculations for nuclear magnetic resonance chemical shifts: A divide-and-conquer approach
Authors: Wang Bing , Brothers Edward N. , van der Vaart Arjan , Merz Kenneth M.
Published: June 2004

A new approach to calculate nuclear magnetic resonance chemical shifts has been implemented at the semiempirical modified neglect of diatomic overlap level using gauge-including atomic orbitals. The perturbed density matrix with respect to the magnetic field is obtained by the diagonalization of the complex Fock matrix using the divide and conquer (DC) method, instead of by solving the computationally expensive coupled perturbed Hartree–Fock equations. Adopting the Patchkovskii and Thiel parameters [S. Patchkovskii and W. Thiel J. Comput. Chem. 20, 1220 (1999)], we were able to reproduce their results for small organic molecules. The errors introduced by DC method are negligible, as shown by the calculations on a series of polyalaine structures. Test calculations on proteins have demonstrated that our approach makes it possible to calculate chemical shifts routinely on systems with hundreds of atoms with good accuracy.
Nonmonotonic temperature dependence of heat capacity through the glass transition within a kinetic model
Authors: Chakrabarti Dwaipayan , Bagchi Biman
Published: June 2004

The heat capacity of a supercooled liquid subjected to a temperature cycle through its glass transition is studied within a kinetic model. In this model, the β process is assumed to be thermally activated and described by a two-level system. The α process is described as a β relaxation mediated cooperative transition in a double well. The overshoot of the heat capacity during the heating scan is well reproduced and is shown to be directly related to delayed energy relaxation in the double well. In addition, the calculated scan rate dependencies of the glass transition temperature Tg and the limiting fictive temperature TfL show qualitative agreement with the known results. Heterogeneity is found to significantly reduce the overshoot of heat capacity. Furthermore, the frequency dependent heat capacity has been calculated within the present framework and found to be rather similar to the experimentally observed behavior of supercooled liquids.
Vibrational delocalization in ammonia aerosol particles
Authors: Jetzki Martin , Bonnamy Anthony , Signorell Ruth
Published: June 2004

The present contribution investigates shape effects and surface effects in the infrared spectra of pure (NH3) and mixed (NH3–CO2 and NH3–NH2D–NHD2–ND3) ammonia particles with sizes between about 1 and 50 nm. The particles investigated have been generated in a collisional cooling cell as aerosols at temperatures between 20 and 80 K. The contribution reveals that only the combination with a microscopic model leads to a comprehensive understanding of the various features observed in the experimental infrared spectra. As one of the major results, the corresponding exciton model explains why pronounced shape effects observed for pure particles only play a minor role in the case of mixed particles.
Adsorption of 1-octanol at the free water surface as studied by Monte Carlo simulation
Authors: Jedlovszky Pál , Varga Imre , Gilányi Tibor
Published: June 2004

The adsorption of 1-octanol at the free water surface has been investigated by Monte Carlo computer simulation. Six different systems, built up by an aqueous and a vapor phase, the latter also containing various number of octanol molecules, have been simulated. The number of the octanol molecules has been chosen in such a way that the octanol surface density varies in a broad range, between 0.27 and 7.83 μmol/m2 in the six systems simulated. For reference, the interfacial system containing bulk liquid octanol in the apolar phase has also been simulated. The results have shown that the formation of hydrogen bonds between the interfacial water and adsorbed octanol molecules is of key importance in determining the properties of the adsorbed layer. At low octanol surface concentration values all the octanol molecules are strongly (i.e., by hydrogen bonds) bound to the aqueous phase, whereas their interaction with each other is negligibly small. Hence, they are preferentially oriented in such a way that their own binding energy (and thus their own free energy) is minimized. In this preferred orientation the O–H bond of the octanol molecule points flatly toward the aqueous phase, declining by about 30° from the interfacial plane, irrespectively from whether the octanol molecule is the H-donor or the H-acceptor partner in the hydrogen bond. Hence, in its preferred orientation the octanol molecule can form at least two low energy hydrogen bonds with water: one as a H-donor and another one as a H-acceptor. Moreover, the preferred orientation of the hydrogen bonded water partners is close to one of the two preferred interfacial water alignments, in which the plane of the water molecule is parallel with the interface. When increasing the octanol surface density, the water surface gets saturated with hydrogen bonded octanols, and hence any further octanol molecule can just simply condense to the layer of the adsorbed octanols. The surface density value at which this saturation occurs is estimated to be about 1.7 μmol/m2. Above this surface density value the hydrogen bonded octanols and their water partners are oriented in such a way that the number of the water–octanol hydrogen bonds is maximized. Hence, the preferred alignment of the O⋯O axes of these hydrogen bonds is perpendicular to the interface. This orientation is far from the optimal alignment of the individual octanol molecules, which is also reflected in the observed fact that, unlike in the case of many other adsorbents, the average molecular binding energy of the adsorbed octanol molecules increases (i.e., becomes less negative) with increasing octanol surface density.
The anomalous shape of the cross section for the formation of SF3+ fragment ions produced by electron impact on SF6 revisited
Authors: Feil S. , Gluch K. , Scheier P. , Becker K. , Märk T. D.
Published: June 2004

The partial ionization cross section for the formation of SF3+ fragment ions following electron impact on SF6 is known to have a pronounced structure in the cross section curve slightly above 40 eV. We used the mass-analyzed ion kinetic energy (MIKE) scan technique to demonstrate the presence of a channel contributing to the SF3+ partial ionization cross section that we attribute to the Coulomb explosion of doubly charged metastable SF42+ ions into two singly charged ions SF3+ and F+, with a threshold energy of about 45.5 eV. Thus the observed unusual shape of the SF3+ partial ionization cross section is the result of two contributions, (i) the direct formation of SF3+ fragment ions via dissociative ionization of SF6 with a threshold energy of 22 eV and (ii) the Coulomb explosion of metastable SF42+ ions with a threshold energy of about 45.5 eV. A detailed analysis of the MIKE spectrum reveals an average kinetic energy release of about 5 eV in the Coulomb explosion of the SF42+ ions with evidence of a second channel corresponding to an average kinetic energy release of about 1.1 eV.
Radical initiated polymerization in a bifunctional mixture via computer simulation
Authors: Diamond Keri L. , Pandey Ras B. , Thames Shelby F.
Published: June 2004

Computer simulations are performed to study the polymerization behavior in a mixture of bifunctional groups such as olefins (A) and acrylates (B) in an effective solvent (a coarse description for vegetable oil derived macromonomers (VOMMs) in solution) on a cubic lattice. A set of interactions between these units and solvent (S) constituents and their relative concentrations (pA, pB, and pS) are considered. Samples are equilibrated with Metropolis algorithm to model the perceived behavior of VOMMs. The covalent bonding between monomeric units is then implemented via reaction pathways initiated by stochastic motion of free radicals (a very small fraction). The rate of reaction shows decay patterns with the time steps (t) with power laws (i.e., Rabαt−r, r≅0.4–0.8), exponential decays (i.e., Rabαe−0.001t), and their combination. Growth of A–B bonding is studied as a function of polymer concentration p=pA+pB for four different model systems appropriate for VOMMs. The data from the free radical initiated simulations are compared to the original simulations with homopolymerization. While most of the data are consistent with experimental observations, the variations are found to be model dependent.
Critical cavities and the kinetic spinodal for superheated liquids
Authors: Punnathanam Sudeep , Corti David S.
Published: June 2004

We present density-functional theory (DFT) calculations for critical cavities inside model superheated liquids with varying intermolecular potentials. Our calculations show that the radius of the critical cavity and the ratio of the work of formation of the critical cavity to the work of formation of the critical bubble as predicted by the classical nucleation theory exhibit universal scaling across similar intermolecular potentials. We then utilize this observed scaling behavior by proposing two new criteria for the kinetic spinodal of superheated liquids. These criteria are based on various properties of the critical cavity as obtained from our DFT studies of the superheated Lenanrd-Jones liquid. Our predictions of the kinetic spinodal compare favorably with experimental data of the limits of superheating for various organic liquids.
Accelerated molecular dynamics: A promising and efficient simulation method for biomolecules
Authors: Hamelberg Donald , Mongan John , McCammon J. Andrew
Published: June 2004

Many interesting dynamic properties of biological molecules cannot be simulated directly using molecular dynamics because of nanosecond time scale limitations. These systems are trapped in potential energy minima with high free energy barriers for large numbers of computational steps. The dynamic evolution of many molecular systems occurs through a series of rare events as the system moves from one potential energy basin to another. Therefore, we have proposed a robust bias potential function that can be used in an efficient accelerated molecular dynamics approach to simulate the transition of high energy barriers without any advance knowledge of the location of either the potential energy wells or saddle points. In this method, the potential energy landscape is altered by adding a bias potential to the true potential such that the escape rates from potential wells are enhanced, which accelerates and extends the time scale in molecular dynamics simulations. Our definition of the bias potential echoes the underlying shape of the potential energy landscape on the modified surface, thus allowing for the potential energy minima to be well defined, and hence properly sampled during the simulation. We have shown that our approach, which can be extended to biomolecules, samples the conformational space more efficiently than normal molecular dynamics simulations, and converges to the correct canonical distribution.
Langevin dynamics in constant pressure extended systems
Authors: Quigley D. , Probert M. I. J.
Published: June 2004

The advantages of performing Langevin dynamics in extended systems are discussed. A simple Langevin dynamics scheme for producing the canonical ensemble is reviewed, and is then extended to the Hoover ensemble. We show that the resulting equations of motion generate the isobaric–isothermal ensemble. The Parrinello–Rahman ensemble is then discussed and we show that despite the presence of intrinsic probability gradients in this system, a Langevin dynamics approach samples the extended phase space in the correct fashion. The implementation of these methods in the ab initio plane wave density functional theory code CASTEP [M. D. Segall, P. L. D. Lindan, M. J. Probert, C. J. Pickard, P. J. Hasnip, S. J. Clarke, and M. C. Payne, J. Phys.: Condens. Matter 14, 2717 (2003)] is demonstrated.
Adsorption and diffusion on a stepped surface: Atomic hydrogen on Pt(211)
Authors: Olsen R. A. , Bădescu Ş. C. , Ying S. C. , Baerends E. J.
Published: June 2004

We present density functional theory calculations for atomic hydrogen interacting with a stepped surface, the Pt(211) surface. The calculations have been performed at the generalized gradient approximation level, using a slab representation of the surface. This is the state-of-the-art method for calculating the interaction of atoms or molecules with metal surfaces, nevertheless only few studies have used it to study atoms or molecules interacting with stepped surfaces, and none, to the best of our knowledge, have considered hydrogen interacting with stepped platinum surfaces. Our goal has been to initiate a systematic study of this topic. We have calculated the full three-dimensional potential energy surface (PES) for the H/Pt(211) system together with the vibrational band structure and vibrational eigenfunctions of H. A deep global minimum of the PES is found for bridge-bonded hydrogen on the step edge, in agreement with experimental results for the similar H/Pt(533) system. All the local vibrational excitations at the global minimum have been identified, and this will serve as a helpful guide to the interpretation of future experiments on this (or similar) system(s). Furthermore, from the calculated PES and vibrational band structure, we identify a number of consequences for the interpretation or modelling of diffusion experiments studying the coverage and directional dependence of atomic hydrogen diffusion on stepped platinum surfaces.
Exploration of the electronic structure of dendrimerlike acetylene-bridged oligothiophenes by correlating Raman spectroscopy, electrochemistry, and theory
Authors: Casado Juan , Pappenfus Ted M. , Mann Kent R. , Hernández Vı́ctor , López Navarrete Juan T.
Published: June 2004

A series of radial thiophene-based structures consisting of a central benzene or thiophene ring surrounded by acetylene-bridged terthienyl arms has been investigated by physical and theoretical methods. Fourier transform Raman spectroscopy of the neutral solids shows that the terthiophene arms are weakly coupled across the core (benzene plus acetylene groups) likely due to cross-conjugation or meta-conjugation effects that may prevent full delocalization. By increasing the number of arms around the central ring, the electronic structure of the molecules seems to be affected only at the core, whereas the outer terthiophene arms remain almost unaltered. Raman spectroelectrochemistry and quantum chemical calculations provide further insight into the charge delocalization of the oxidized species. There is no evidence to suggest that these oxidized forms, obtained upon electrochemical doping of the molecules, show charge delocalization across the core.
Fragmentation dynamics of ionized neon trimer inside helium nanodroplets: A theoretical study
Authors: Bonhommeau David , Viel Alexandra , Halberstadt Nadine
Published: June 2004

We report a theoretical study of the fragmentation dynamics of Ne3+ inside helium nanodroplets, following vertical ionization of the neutral neon trimer. The motion of the neon atoms is treated classically, while transitions between the electronic states of the ionic cluster are treated quantum mechanically. A diatomics-in-molecules description of the potential energy surfaces is used, in a minimal basis set consisting of three effective p orbitals on each neon atom for the missing electron. The helium environment is modeled by a friction force acting on the neon atoms when their speed exceeds the Landau velocity. A reasonable range of values for the corresponding friction coefficient is obtained by comparison with existing experimental measurements.
Liquids confined in wedge shaped pores: Nonuniform pressure induced by pore geometry
Authors: Cámara Luis G. , Bresme Fernando
Published: June 2004

Lennard-Jones liquids confined in wedge shaped nanopores are investigated using molecular dynamics computer simulations. We show that small deviations from the parallel slit geometry result in nonuniform pressures and density profiles along the pore. In conditions of high confinement and thermodynamic states close to the triple point, wedge shaped pores can induce the formation of solid phases in specific regions within the nanopore.
Phylogenetic relationships of the Australo-Papuan Liasis pythons (Reptilia : Macrostomata), based on mitochondrial DNA
Authors: Rawlings Lesley H. , Barker David , Donnellan Stephen C.
Published: June 2004

The genus Liasis comprises two groups of pythons, the olive python, Liasis olivaceus, and the water pythons L. fuscus and L. mackloti. We used partial mitochondrial control region DNA sequences to examine (a) the phylogeography of water pythons from five Indonesian Lesser Sunda islands, New Guinea, and northern Australia, (b) the relationships of the two subspecies of olive pythons, and (c) the relationship of the Papuan python, Apodora papuana, with the species of Liasis. Maximum likelihood, parsimony and distance analyses showed that A. papuana is the sister lineage to all Liasis and that Liasis fuscus/L. mackloti and L. olivaceus are separate lineages. There is also support for the reciprocal monophyly of the two olive python subspecies, L. olivaceus barroni and L. o. olivaceus, and for distinction of island populations described previously as L. mackloti dunni from Wetar and L. mackloti savuensis from Sawu. These two island populations are as equally distinct as the populations from the island cluster of Babar/Semau/Timor. There is strong support for the recognition of two lineages ('eastern' and 'western') of water pythons in Australia. We propose that the drier interior of the Plio-Pleistocene land bridge between Australia and New Guinea acted as a barrier to gene flow, influencing the genetic divergence between the 'eastern' and 'western' lineages of the semi-aquatic water pythons.
Life history of the white-breasted robin, Eopsaltria georgiana (Petroicidae), in south-western Australia
Authors: Russell E. M. , Brown the late R. J. , Brown M. N.
Published: June 2004

The white-breasted robin, Eopsaltria georgiana, is endemic to south-western Australia. We studied breeding, dispersal and survival in known groups from 1978 until 1987, with some groups followed until 1992, in Eucalyptus diversicolor (karri) forest near Manjimup, Western Australia. E. georgiana bred cooperatively, with 66% of groups including one or more birds in addition to the breeding pair (mean group size 3.1); these helpers were predominantly males and assisted the senior male in feeding the female on the nest and the young and defending the territory. The survival of adults was high (males 86%; females 79%). Breeding territories and groups persisted from year to year, although in the non-breeding season, males ranged more widely. Dispersal was female-biased; most females and some males dispersed in their first year. Divorce was rare; breeding males that disappeared were replaced by a helper from within the group if one was present, and females were replaced from outside the group. Eggs were laid between July and December. Clutch size was almost always 2, incubation lasted 16–17 days and nestlings fledged 13–14 days later. Juveniles were dependent on adult provisioning for 6–8 weeks. We found no parasitism by cuckoos. Of 429 nests found, 74% fledged at least one young, and overall nesting success calculated by the Mayfield method was 63%. The median time between initiation of two successive clutches was 54 days, and 52% of females renested after fledging one brood; at least two broods per year were fledged by 44% of females. Groups produced a mean of 2.8 fledglings, 1.3 independent young and 0.7 yearlings per year. The most productive groups were those with two or more helpers on high-quality territories, but we could not separate the effects of helpers and territory quality. E. georgiana has the 'slow' life history typical of many Australian passerines – cooperative breeding, sedentary, resident all year round in an equable habitat that promotes high survival of breeding adults. Their low reproductive rate produces a small crop of yearlings, some of which may stay in the parental home range.
Manipulation of light signal transduction as a means of modifying fruit nutritional quality in tomato
Authors: Liu Yongsheng , Roof Sherry , Ye Zhibiao , Barry Cornelius , van Tuinen Ageeth , Vrebalov Julia , Bowler Chris , Giovannoni Jim
Published: June 2004

Fruit constitutes a major component of human diets, providing fiber, vitamins, and phytonutrients. Carotenoids are a major class of compounds found in many fruits, providing nutritional benefits as precursors to essential vitamins and as antioxidants. Although recent gene isolation efforts and metabolic engineering have primarily targeted genes involved in carotenoid biosynthesis, factors that regulate flux through the carotenoid pathway remain largely unknown. Characterization of the tomato high-pigment mutations (
hp1
and
hp2
) suggests the manipulation of light signal transduction machinery may be an effective approach toward practical manipulation of plant carotenoids. We demonstrate here that
hp1
alleles represent mutations in a tomato
UV
-
DAMAGED DNA-BINDING PROTEIN 1
(
DDB1
) homolog. We further demonstrate that two tomato light signal transduction genes,
LeHY5
and
LeCOP1LIKE
, are positive and negative regulators of fruit pigmentation, respectively. Down-regulated
LeHY5
plants exhibit defects in light responses, including inhibited seedling photomorphogenesis, loss of thylakoid organization, and reduced carotenoid accumulation. In contrast, repression of
LeCOP1LIKE
expression results in plants with exaggerated photomorphogenesis, dark green leaves, and elevated fruit carotenoid levels. These results suggest genes encoding components of light signal transduction machinery also influence fruit pigmentation and represent genetic tools for manipulation of fruit quality and nutritional value.
Selective pressures on the olfactory receptor repertoire since the human-chimpanzee divergence
Authors: Gimelbrant Alexander A. , Skaletsky Helen , Chess Andrew
Published: June 2004

The availability of the sequence of the chimpanzee genome provides an opportunity to examine human genes and their chimpanzee orthologs and to analyze selective pressures that have been shaping the olfactory receptor repertoire since the human-chimpanzee divergence. We determined the ratio of nonsynonymous to synonymous changes for each of 186 orthologous pairs and then examined how the distribution of these ratios compares with the distribution expected under neutral drift. Consistent with the diminishing importance of olfaction for these species, we find no evidence for positive selection and we find evidence of weak purifying selection affecting over half of the repertoire.
Rapid and sequential movement of individual chromosomal loci to specific subcellular locations during bacterial DNA replication
Authors: Viollier Patrick H. , Thanbichler Martin , McGrath Patrick T. , West Lisandra , Meewan Maliwan , McAdams Harley H. , Shapiro Lucy
Published: June 2004

The chromosomal origin and terminus of replication are precisely localized in bacterial cells. We examined the cellular position of 112 individual loci that are dispersed over the circular
Caulobacter crescentus
chromosome and found that in living cells each locus has a specific subcellular address and that these loci are arrayed in linear order along the long axis of the cell. Time-lapse microscopy of the location of the chromosomal origin and 10 selected loci in the origin-proximal half of the chromosome showed that during DNA replication, as the replisome sequentially copies each locus, the newly replicated DNA segments are moved in chronological order to their final subcellular destination in the nascent half of the predivisional cell. Thus, the remarkable organization of the chromosome is being established while DNA replication is still in progress. The fact that the movement of these 10 loci is, like that of the origin, directed and rapid, and occurs at a similar rate, suggests that the same molecular machinery serves to partition and place many, if not most, chromosomal loci at defined subcellular sites.
T cell receptor-ligand interactions: A conformational preequilibrium or an induced fit
Authors: Gakamsky Dmitry M. , Luescher Immanuel F. , Pecht Israel
Published: June 2004

Kinetic parameters of T cell receptor (TCR) interactions with its ligand have been proposed to control T cell activation. Analysis of kinetic data obtained has so far produced conflicting insights; here, we offer a consideration of this problem. As a model system, association and dissociation of a soluble TCR (sT1) and its specific ligand, an azidobenzoic acid derivative of the peptide SYIPSAEK-(ABA)I (residues 252-260 fromPlasmodium bergheicircumsporozoite protein), bound to class I MHC H-2Kd-encoded molecule (MHCp) were studied by surface plasmon resonance. The association time courses exhibited biphasic patterns. The fast and dominant phase was assigned to ligand association with the major fraction of TCR molecules, whereas the slow component was attributed to the presence of traces of TCR dimers. The association rate constant derived for the fast phase, assuming a reversible, single-step reaction mechanism, was relatively slow and markedly temperature-dependent, decreasing from 7.0 × 103at 25°C to 1.8 × 102M-1·s-1at 4°C. Hence, it is suggested that these observed slow rate constants are the result of unresolved elementary steps of the process. Indeed, our analysis of the kinetic data shows that the time courses of TCR-MHCp interaction fit well to two different, yet closely related mechanisms, where an induced fit or a preequilibrium of two unbound TCR conformers are operational. These mechanisms may provide a rationale for the reported conformational flexibility of the TCR and its unusual ligand recognition properties, which combine high specificity with considerable crossreactivity.
Glycaemic index of selected staples commonly eaten in the Caribbean and the effects of boiling v. crushing
Authors: Dan Ramdath D. , Isaacs Renée L. C. , Teelucksingh Surujpal , Wolever Thomas M. S.
Published: June 2004

Integrating information about the glycaemic index (GI) of foods into the Caribbean diet is limited by the lack of data. Therefore, we determined the GI of eight staple foods eaten in the Caribbean and the effect on GI of crushing selected tubers. Groups of eight to ten healthy volunteers participated in three studies at two sites. GI was determined using a standard method with white bread and adjusted relative to glucose. The mean area under the glucose response curve elicited by white bread was similar for the different groups of subjects. In study 1, the GI of cassava (Manihot esculenta; 94 (SEM 11)) was significantly higher than those of breadfruit (Artocarpus altilis; 60 (SEM 9)), cooking ‘green’ banana (Musa spp.; 65 (SEM 11)) and sadha roti (65 (SEM 9)) (P=0·018). There was no significant difference in the GI of the foods in study 2: dasheen (Colocasia esculenta var. esculenta; 77 (SEM 10)), eddoes (Colocasia esculenta var. antiquorum; 61 (SEM 10)), Irish potato (Solanum tuberosum; 71 (SEM 8)), tannia (Xanthosoma sagittifolium; 60 (SEM 5)) and white yam (Dioscorea alata; 62 (SEM 6)), and, in study 3, crushing did not significantly affect the GI of dasheen, tannia or Irish potato. However, when the results from studies 2 and 3 were pooled, the GI of dasheen (76 (SEM 7)) was significantly greater than that of tannia (55 (SEM 5); P=0·015) with potato being intermediate (69 (SEM 6)). We conclude that dasheen and cassava are high-GI foods, whereas the other tubers studied and sadha roti are intermediate-GI foods. Given the regular usage of cassava and dasheen in Caribbean diets we speculate that these diets would tend to be high GI, although this could be reduced by foods such as sadha roti and white yam. The range of GI between the staples is sufficiently large that health benefits may be accrued by replacing high-GI staples with intermediate-GI staples in the Caribbean diet.
Effect of Oral Gavage Dosing Regimens in Female Tg rasH2 Transgenic Mice
Authors: Morton Daniel , Sellers Rani S. , Furst Sylvia M. , Hawley Kristen D. , May Jeffrey R.
Published: June 2004

Female Tg rasH2 (CB6F1/Jic-TgrasH2@Tac) mice were administered water once daily, water twice daily with 8 or 12 hours between doses, 1% sodium dodecyl sulfate in water (1% SDS) once daily, or 1% SDS twice daily with 12 hours between doses by oral gavage at volumes of 10 ml/kg/day for 28 or 29 consecutive days. A control group of mice received no treatment and no sham manipulation. There were no significant differences in body weight or food consumption between treated groups and untreated control mice. Mean weights of spleens, livers, and thymuses were lower than control values in most groups of mice subjected to gavage. Focal or multifocal loss of thymic cortical architecture was observed in 13 of 50 mice distributed among all groups (including naïve controls), however only in one instance was this finding suggestive of a precursor to neoplasia. This study demonstrated that Tg rasH2 mice can tolerate once or twice daily gavage dosing with water or vehicle containing 1% SDS. Loss of thymic cortical architecture was a common incidental finding in female Tg rasH2 mice.
Tumor Spectrum in the p53 Heterozygous Zeta Globin-Promoted Tg.AC (v-Ha-ras) Bitransgenic Mouse Model
Authors: Martin Keith R. , Jokinen Michael P. , Honeycutt Hayden P. , Quinn Anita , Kari Frank W. , Barrett J. Carl , French John E.
Published: June 2004

The use of a bitransgenic mouse model for cancer is an effective approach for studying the impact of specific carcinogens and the occurrence of tissue-specific lesions. We studied the novel p53 heterozygous zeta globin-promoted Tg.AC (v-Ha-ras) mouse model because these mice contain a carcinogen-inducible ras oncogene and one functional p53 tumor suppressor allele, both of which occur frequently in human cancers. Our aim was to characterize the short-term control and chemically induced tumor spectrum in this novel model. Mice were placed on basal semipurified diet containing 20% soy protein for 2 weeks prior to random allocation to groups. Subsequently, 15 male and 15 female mice were administered corn oil vehicle alone or containing benzo(a)pyrene (20 mg/kg body weight) via oral gavage 2 times per week for 10 weeks with subsequent observation for 18 weeks. Mice exhibited lesions characteristic of FVB/N, p53 heterozygous and Tg.AC mouse models. However, an array of unique, novel lesions were observed including uterine leiomyosarcomas, mammary gland carcinomas, mammary squamous cell carcinomas, and parotid salivary gland carcinomas suggesting tissue-specific interactions of the 2 genotypes. Thus, this bitransgenic model may provide further insight into the mechanistic interaction of 2 genes commonly mutated in neoplasia.
Bone Neoplasms in F344 Rats Given Teriparatide [rhPTH(1-34)] Are Dependent on Duration of Treatment and Dose
Authors: Vahle John L. , Long Gerald G. , Sandusky George , Westmore Michael , Ma Yanfei Linda , Sato Masahiko
Published: June 2004

A long-term study was conducted in female F344 rats to determine the relative importance of dose, treatment duration, and age at initiation of treatment on the incidence of teriparatide [rhPTH[1-34)]-induced bone proliferative lesions. Treatment groups consisted of different combinations of dose (0, 5, or 30 μg/kg/d), treatment duration (6, 20, or 24 months) and age at initiation of treatment (2 or 6 months of age). The primary endpoints were the incidence of bone neoplasms and effects on bone mass and structure as evaluated by quantitative computed tomography and histomorphometery. Significant increases in the incidence of bone tumors (osteoma, osteoblastoma, and osteosarcoma) occurred in rats treated with 30 μg/kg for 20 or 24 months. No neoplasms were found when the 5 μg/kg treatment was initiated at 6 months of age and continued for either 6 or 20 months (up to 70% of life span). This treatment regimen defined a “no-effect” dose for neoplasm formation that nevertheless resulted in substantial increases in bone mass. These results demonstrate that treatment duration and administered dose are the most important factors in the teriparatide-induced bone tumors in rats.
2'‐Functionalized Nucleic Acids as Structural Tools in Molecular Biology
Authors: Zatsepin Timofei S. , Gait Michael J. , Oretskaya Tatiana S.
Published: June 2004

Modified oligonucleotides bearing 2'‐reactive groups or 2'‐conjugated molecules have found wide application as structural tools in molecular biology. Of principal interest has been the use of 2'‐reactive oligonucleotides for cross‐linking with biomolecules and of 2'‐conjugated oligonucleotides in hybridization assays. In this review we compare a range of electrophilic, nucleophilic and photoreactive groups for cross‐linking and conjugation studies.
IUBMB Life, 56: 209‐214, 2004
Bld10p, a novel protein essential for basal body assembly in Chlamydomonas
Authors: Matsuura Kumi , Lefebvre Paul A. , Kamiya Ritsu , Hirono Masafumi
Published: June 2004

How centrioles and basal bodies assemble is a long-standing puzzle in cell biology. To address this problem, we analyzed a novel basal body-defective Chlamydomonas reinhardtii mutant isolated from a collection of flagella-less mutants. This mutant, bld10, displayed disorganized mitotic spindles and cytoplasmic microtubules, resulting in abnormal cell division and slow growth. Electron microscopic observation suggested that bld10 cells totally lack basal bodies. The product of the BLD10 gene (Bld10p) was found to be a novel coiled-coil protein of 170 kD. Immunoelectron microscopy localizes Bld10p to the cartwheel, a structure with ninefold rotational symmetry positioned near the proximal end of the basal bodies. Because the cartwheel forms the base from which the triplet microtubules elongate, we suggest that Bld10p plays an essential role in an early stage of basal body assembly. A viable mutant having such a severe basal body defect emphasizes the usefulness of Chlamydomonas in studying the mechanism of basal body/centriole assembly by using a variety of mutants.
The Drosophila pericentrin-like protein is essential for cilia/flagella function, but appears to be dispensable for mitosis
Authors: Martinez-Campos Maruxa , Basto Renata , Baker James , Kernan Maurice , Raff Jordan W.
Published: June 2004

Centrosomes consist of a pair of centrioles surrounded by an amorphous pericentriolar material (PCM). Proteins that contain a Pericentrin/AKAP450 centrosomal targeting (PACT) domain have been implicated in recruiting several proteins to the PCM. We show that the only PACT domain protein in Drosophila (the Drosophila pericentrin-like protein [D-PLP]) is associated with both the centrioles and the PCM, and is essential for the efficient centrosomal recruitment of all six PCM components that we tested. Surprisingly, however, all six PCM components are eventually recruited to centrosomes during mitosis in d-plp mutant cells, and mitosis is not dramatically perturbed. Although viable, d-plp mutant flies are severely uncoordinated, a phenotype usually associated with defects in mechanosensory neuron function. We show that the sensory cilia of these neurons are malformed and the neurons are nonfunctional in d-plp mutants. Moreover, the flagella in mutant sperm are nonmotile. Thus, D-PLP is essential for the formation of functional cilia and flagella in flies.
Cell cycle progression after cleavage failure
Authors: Uetake Yumi , Sluder Greenfield
Published: June 2004

Failure of cells to cleave at the end of mitosis is dangerous to the organism because it immediately produces tetraploidy and centrosome amplification, which is thought to produce genetic imbalances. Using normal human and rat cells, we reexamined the basis for the attractive and increasingly accepted proposal that normal mammalian cells have a “tetraploidy checkpoint” that arrests binucleate cells in G1, thereby preventing their propagation. Using 10 μM cytochalasin to block cleavage, we confirm that most binucleate cells arrest in G1. However, when we use lower concentrations of cytochalasin, we find that binucleate cells undergo DNA synthesis and later proceed through mitosis in >80% of the cases for the hTERT-RPE1 human cell line, primary human fibroblasts, and the REF52 cell line. These observations provide a functional demonstration that the tetraploidy checkpoint does not exist in normal mammalian somatic cells.
Regulation of a formin complex by the microtubule plus end protein tea1p
Authors: Feierbach Becket , Verde Fulvia , Chang Fred
Published: June 2004

The plus ends of microtubules have been speculated to regulate the actin cytoskeleton for the proper positioning of sites of cell polarization and cytokinesis. In the fission yeast Schizosaccharomyces pombe, interphase microtubules and the kelch repeat protein tea1p regulate polarized cell growth. Here, we show that tea1p is directly deposited at cell tips by microtubule plus ends. Tea1p associates in large “polarisome” complexes with bud6p and for3p, a formin that assembles actin cables. Tea1p also interacts in a separate complex with the CLIP-170 protein tip1p, a microtubule plus end–binding protein that anchors tea1p to the microtubule plus end. Localization experiments suggest that tea1p and bud6p regulate formin distribution and actin cable assembly. Although single mutants still polarize, for3Δbud6Δtea1Δ triple-mutant cells lack polarity, indicating that these proteins contribute overlapping functions in cell polarization. Thus, these experiments begin to elucidate how microtubules contribute to the proper spatial regulation of actin assembly and polarized cell growth.
Tumor Rejection Induced by CD70-mediated Quantitative and Qualitative Effects on Effector CD8+ T Cell Formation
Authors: Arens Ramon , Schepers Koen , Nolte Martijn A. , van Oosterwijk Michiel F. , van Lier René A.W. , Schumacher Ton N.M. , van Oers Marinus H.J.
Published: June 2004

In vivo priming of antigen-specific CD8+ T cells results in their expansion and differentiation into effector T cells followed by contraction into a memory T cell population that can be maintained for life. Recent evidence suggests that after initial antigenic stimulation, the magnitude and kinetics of the CD8+ T cell response are programmed. However, it is unclear to what extent CD8+ T cell instruction in vivo is modulated by costimulatory signals. Here, we demonstrate that constitutive ligation of the tumor necrosis factor receptor family member CD27 by its ligand CD70 quantitatively augments CD8+ T cell responses to influenza virus infection and EL-4 tumor challenge in vivo by incrementing initial expansion and maintaining higher numbers of antigen-specific T cells in the memory phase. Concomitantly, the quality of antigen-specific T cells improved as evidenced by increased interferon (IFN)-γ production and a greater cytotoxic potential on a per cell basis. As an apparent consequence, the superior effector T cell formation induced by CD70 protected against a lethal dose of poorly immunogenic EL4 tumor cells in a CD8+ T cell– and IFN-γ–dependent manner. Thus, CD70 costimulation enhances both the expansion and per cell activity of antigen-specific CD8+ T cells.
In Vitro–expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes
Authors: Tang Qizhi , Henriksen Kammi J. , Bi Mingying , Finger Erik B. , Szot Greg , Ye Jianqin , Masteller Emma L. , McDevitt Hugh , Bonyhadi Mark , Bluestone Jeffrey A.
Published: June 2004

The low number of CD4+ CD25+ regulatory T cells (Tregs), their anergic phenotype, and diverse antigen specificity present major challenges to harnessing this potent tolerogenic population to treat autoimmunity and transplant rejection. In this study, we describe a robust method to expand antigen-specific Tregs from autoimmune-prone nonobese diabetic mice. Purified CD4+ CD25+ Tregs were expanded up to 200-fold in less than 2 wk in vitro using a combination of anti-CD3, anti-CD28, and interleukin 2. The expanded Tregs express a classical cell surface phenotype and function both in vitro and in vivo to suppress effector T cell functions. Most significantly, small numbers of antigen-specific Tregs can reverse diabetes after disease onset, suggesting a novel approach to cellular immunotherapy for autoimmunity.
Short-lived Plasmablasts and Long-lived Plasma Cells Contribute to Chronic Humoral Autoimmunity in NZB/W Mice
Authors: Hoyer Bimba F. , Moser Katrin , Hauser Anja E. , Peddinghaus Anette , Voigt Caroline , Eilat Dan , Radbruch Andreas , Hiepe Falk , Manz Rudolf A.
Published: June 2004

The current view holds that chronic autoimmune diseases are driven by the continuous activation of autoreactive B and T lymphocytes. However, despite the use of potent immunosuppressive drugs designed to interfere with this activation the production of autoantibodies often persists and contributes to progression of the immunopathology. In the present study, we analyzed the life span of (auto)antibody-secreting cells in the spleens of NZB × NZW F1 (NZB/W) mice, a murine model of systemic lupus erythematosus. The number of splenic ASCs increased in mice aged 1–5 mo and became stable thereafter. Less than 60% of the splenic (auto)antibody-secreting cells were short-lived plasmablasts, whereas 40% were nondividing, long-lived plasma cells with a half-life of >6 mo. In NZB/W mice and D42 Ig heavy chain knock-in mice, a fraction of DNA-specific plasma cells were also long-lived. Although antiproliferative immunosuppressive therapy depleted short-lived plasmablasts, long-lived plasma cells survived and continued to produce (auto)antibodies. Thus, long-lived, autoreactive plasma cells are a relevant target for researchers aiming to develop curative therapies for autoimmune diseases.
In this issue
Authors: Cook Alan
Published: June 2004

Introduction to the July 1997 issue of
Notes and Record
On the shapes of Newton's revolving orbits
Authors: Lynden-Bell D. , Lynden-Bell R. M.
Published: June 2004

Newton's beautiful theorem on revolving orbits is described in propositions 43 and 44 of
Principia
. From Motte's translation revised by Cajori (see also Chandrasekhar, who first drew our attention to this theorem).

43. It is required to make a body move in a curve that revolves about the centre of force in the same manner as another body in the same curve at rest

4. The difference of the forces by which two bodies may be made to move equally, one in a fixed, the other in the same orbit revolving varies inversely as the cubes of their common altitudes (radii).

Those who read these propositions without consulting the expositions that follow them are likely to believe that Newton was considering two orbits, the first in fixed axes and the second in uniformly rotating axes. This is not the case. Indeed, that could not be so because unless the orbits were circular, the second particle would not then sweep out equal areas in equal times relative to fixed axes, so the force could not be central. Newton's subtlety lies in choosing the rate of rotation of the axes proportional to the øof the particle in the fixed orbit, where ø is the azimuth. With that construction the second particle, when seen from fixed axes, sweeps in equal times equal areas proportional to those swept by the first.

A Keplerian ellipse in fixed axes will generate the same ellipse in Newton's nonuniformly rotating axes when we add an inverse cube force. But what shape will that ellipse make relative to axes rotating uniformly at the same mean rate as Newton's?
The Royal Society's portrait of Joseph Banks
Authors: Fara P.
Published: June 2004

The year before he died, although disingenuously insisting that ‘I do not feel as if Vanity was a Prominent trée in my character’, Joseph Banks vituperatively rejected the ‘intended Brittle Compliment’ of a commemorative Sévres vase because he disapproved of its proposed illustrations. Just as Banks policed Enlightenment visions of the lands he had explored and the specimens he had collected, so too he carefully monitored the images of himself that became available for public consumption. Recognizing the propagandizing power of visual representations, during his long reign as President of the Royal Society from 1778–1820, he influenced how he was shown in his own portraits, and commissioned paintings celebrating his colleagues' achievements, such as Nathaniel Dance's picture showing James Cook advertising his improved Pacific chart.
Sir Edward Appleton and early ionosphere research
Authors: Wilkes M. V.
Published: June 2004

The earliest suggestion that there might be a conducting layer in the earth's atmosphere was made in 1839 by Gauss, who was concerned to explain the diurnal geomagnetic phenomena, and who pointed out that a possible hypothesis was that they arose from electric currents encircling the earth somewhere in the atmosphere. However, at that time, no mechanism to account for the existence of a conducting layer could be suggested, nor was there any knowledge of how air could become conducting; indeed, until ionizing radiation began to be studied, it was even suggested that air naturally became conducting at low pressure.

It was soon apparent that the propagation of radio waves beyond the horizon could not be explained as the result of diffraction. Heaviside and Kennelly, at about the same time, both proposed that a conducting layer in the atmosphere was responsible. It was Appleton who first showed, by an elegant and well planned series of experiments, that this was indeed the case; or to put it more precisely, that at a point distant from the transmitter there was, in addition to a wave received along the surface of the earth, a second wave descending from the sky.
The Crocodile and the Elephant
Authors: Mackintosh A. R.
Published: June 2004

In 1907 Ernest Rutherford (later named ‘The Crocodile’ by Peter Kapitza), 36 years old and already a world–famous physicist, moved from McGill University in Montreal, Canada, to the University of Manchester, England. In the same year Niels Bohr (later known by some as ‘The Elephant’––he was one of the very few non–royal recipients of the Order of the Elephant), a 22–year–old student at the University of Copenhagen, received the gold medal of the Royal Danish Academy for his first research project, an experimental and theoretical study of water jets. During the next 30 years, until Rutherford's death in 1937, these two great scientists dominated quantum physics. Rutherford was the father of nuclear physics; together they founded atomic physics; and, with their students and colleagues, they were responsible for the great majority of the decisive advances made in the inter–war years. This lecture tells the story of the development in quantum physics, and makes some comparisons between Bohr and Rutherford–as men and scientists–drawing especially on their extensive correspondence between 1912 and 1937, the material that Bohr gathered in connection with the publication in 1961 of his Rutherford Memorial Lecture, the interviews that he gave just before his death in 1962, and other published and unpublished material from the Niels Bohr Archive in Copenhagen.
Essay review: Seeds of the scientific revolution
Authors: Cook Alan
Published: June 2004

Edward Grant,
The Foundations of Modern Science in the Middle Ages, Their Religious, Institutional and Intellectual Contexts
, Cambridge University Press, 1996. Pp. xiv+247. ISBN 0–521–56137–X

Benedino Gemelli,
Aspetti dell'Atomismo classico nella Filosofia di Francis Bacon e nel Seicento, Accademia toscana di Scienze e Lettere ‘La Colombaria’,‘Studi’ CLII
, Olschki, Firenze, 1996. Pp. 433, Lit 86 000. ISBN 88–222–4460–5