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Although DNA polymerase eta (Pol eta) and other Y family polymerases differ in sequence and function from classical DNA polymerases, they all share a similar right-handed architecture with the palm, fingers, and thumb domains. Here, we examine the role in Saccharomyces cerevisiae Pol eta of three conserved residues, tyrosine 64, arginine 67, and lysine 279, which come into close contact with the triphosphate moiety of the incoming nucleotide, in nucleotide incorporation. We find that mutational alteration of these residues reduces the efficiency of correct nucleotide incorporation very considerably. The high degree of conservation of these residues among the various Y family DNA polymerases suggests that these residues are also crucial for nucleotide incorporation in the other members of the family. Furthermore, we note that tyrosine 64 and arginine 67 are functionally equivalent to the deoxynucleotide triphosphate binding residues arginine 518 and histidine 506 in T7 DNA polymerase, respectively.

Mercury's magnetosphere only partially protects its surface from solar particles. When a solar energetic particle (SEP) event encounters Mercury, a significant flux of energetic particles will reach Mercury's surface which can change Mercury's exosphere. In this paper, we describe some of the consequences of the encounter of a SEP event with Mercury before and few hours after the shock associated with such an event reaches Mercury. Energetic ions and electrons with energy between 10 keV and 10 MeV are followed across a model of Mercury's magnetosphere (J. Geophys. Res. 103 (1998) 9113). The effects of such an encounter on the ion and neutral exospheres are estimated for one particular gradual proton event reported by Reames et al. (Astrophys. J. 483 (1997a) 515) and scaled to Mercury's orbit. After the arrival of these SEP at Mercury, a population of quasi-trapped energetic ions and electrons is expected close to Mercury which is stable for hours after their arrival at Mercury. A significant dawn/dusk charge separation is observed. A fraction of the initial energetic particles (∼10%) impact the surface with a spatial distribution that exhibits north/south and dawn/dusk asymmetries. The flux of particles impacting the surface and the ability of a quasi-trapped population to be maintained near Mercury are highly dependent on the Bz sign of the interplanetary magnetic field. The impacting SEP can eject a non-uniform distribution of sodium atoms into Mercury's exosphere and can be the origin of several exospheric features observed during last decade.

In this review we provide the data needed to interpret remote spectroscopic studies of O2 molecules embedded in the icy surfaces of outer solar system bodies. O2 produced by radiolysis has been seen in the gas phase and as the so-called ‘solid O2’ trapped in the icy surfaces of Ganymede, Europa and Callisto. It may also have been indirectly observed on a number of objects by its radiolysis product, O3. These observations indicate the importance of O2 for understanding the chemical processes occurring on icy outer solar system surfaces. Therefore, the published absorption spectra of gaseous, liquid and solid O2 and of O2 embedded in H2O ice are reviewed in some detail. Particular emphasis has been placed on the presentation of transition probabilities for the various O2 spectral series so that their relative importances can be assessed when they are used for modelling the radiation chemistry occurring in such environments.

Dissociation and doubly differential cross sections are calculated for N+N2 at near-threshold collision energies using a semiclassical wave packet method in which the vibrational motion of the molecule is treated quantum mechanically and the rotational and translational motions are treated classically. A three-bodied London–Eyring–Polanyi–Sato potential energy surface is used and results compared to those obtained using a purely repulsive power law potential. For a comparison of results, cross sections are also calculated using pure classical mechanics.

International audience; Sputtering and decomposition of Europa's surface by energetic ions and electrons produce an atmosphere. Here we use a 3D Monte Carlo simulation, including collisions with the background O2 atmosphere, to describe recent measurements of the sodium component of the atmosphere. By constraining the model with the observational data, we attempt to reconstruct the source processes, the energy distribution, and the flux of the ejected sodium. We confirm that electronic sputtering from ice-rich regions dominates the ejecta and that Europa loses between 5 and 10×106 Na cm−2 s−1. This is about one order of magnitude more sodium than that implanted from the jovian magnetosphere.

Ion bombardment of surfaces at an angle with respect to the surface normal produces surface modification with more varied and rich features than normal incidence bombardment. This allows more possibilities for nanopatterning and surface processing. Megaelectronvolt ion bombardment of insulators can create a track of electronic excitations which can decay non-radiatively and couple to the lattice, leading to sputtering and crater creation. Using molecular dynamics simulations we present a systematic study of the craters produced by a cylindrical track of excitations with its axis at several angles with respect to the surface normal (in the range Θ =0–80°). We also use different energy densities inside the track, from 0.5 nU to 12.5 nU , where n is the density of the material and U its binding energy. Crater length is found to vary as cos −1 Θ .

Sputtering from grains with a size of tens of nanometers is important in a number of astrophysical environments having a variety of plasma properties and can have applications in nano-technology. Since energy deposition by incident ions or electrons can create `hot' regions in a small grain, thermal spike (TS) models have been applied to estimate the sputtering. The excitations produced by a fast ion are often assumed to form a `hot' cylindrical track. In this paper we use molecular dynamics (MD) calculations to describe the energy transport and sputtering due to the creation of a `hot' track in a grain with one quarter million atoms. We show the enhancement due to grain size and find that TS models work over a limited range of excitation densities. Discrepancies of several orders of magnitude are found when comparing our MD results for sputtering of small dust grains to those obtained by the astrophysical community using spike models.

We measured the rate of sulfate anion production for cyclo-octal sulfur grains in frozen water at temperatures, energies, and dose rates appropriate for Europa using energetic electrons.

Mixtures of sucrose (a lyoprotectant) and mannitol (a bulking agent) have been investigated as excipients for the lyophilization of proteins. Four proteins under development have been successfully lyophilized in a formulation of 4% mannitol and 1% sucrose using a lyophilization cycle that produces a cake of crystalline mannitol and amorphous sucrose. The crystalline mannitol allows primary drying to be performed with a product temperature of −10°C even though the sucrose is amorphous and, by itself, would have required primary drying below −35°C to avoid cake collapse. Formation of an unstable mannitol hydrate is avoided by conducting secondary drying at 40°C or higher. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 914–922, 2002

In this paper we discuss the impact of e‐commerce on the design and construction industry, with specific reference to how information technology will affect competition and competitive advantage in the industry. This paper continues the exploration of a concept that we have been working on for several years, namely ‘…that information technology is evolving from a tool that incrementally improves “back‐office” productivity to an essential component of strategic positioning that may alter the basic economics, organizational structure and operational practices of facility management organizations and their interactions with service providers (architects, engineers and constructors)’ (Johnson & Clayton, Automation in Construction, 8, 1998, 3). We first review industry trends and then develop a generalized model for thinking about strategy and e‐commerce based on our previous research as well as the well‐known framework developed by Michael Porter. Next we apply this framework to the discussion of several case studies and draw preliminary conclusions about the viability of the model for future research.

International audience; The sputtering and decomposition of the surface of Europa by fast ions and electrons lead to the production of an atomosphere containing sodium and potassium atoms. Here time-of-flight energy distributions are measured for Na and K sputtered from a vapor-deposited ice by 200-eV electrons. These data are then used in a Monte Carlo simulation for alkalis in Europa's atmosphere. Na/K ratios versus distance from Europa are calculated and compared to the recent observations in the range 6 to 18 Europan radii from the surface. Normalizing to the observations, the Na/K ratio for the loss rates is ∼27 and the ratio for the average surface source rates is ∼20. These ratios are very different from the Na/K ratio at Io and are larger than the Na/K ratio suggested for Europa's putative subsurface ocean, consistent with fractionation on freezing and upwelling of ocean material.

Interplanetary space is a cosmic laboratory for surface scientists. Energetic photons, ions and electrons from the solar wind, together with galactic and extragalactic cosmic rays, constantly bombard surfaces of planets, planetary satellites, dust particles, comets and asteroids. Many of these bodies exist in ultrahigh vacuum environments, so that direct particle–surface collisions dominate the interactions. In this article, we discuss the origins of the very tenuous planetary atmospheres observed on a number of bodies, space weathering of the surface of asteroids and comets, and magnetospheric processing of the surfaces of Jupiter’s icy satellites. We emphasize non-thermal processes and the important relationships between surface composition and the gas phase species observed. We also discuss what laboratory and computational modeling should be done to support the current and future space missions––e.g. the Genesis mission to recover solar wind particles, the Cassini mission to probe Saturn, the Europa Lander mission to explore the subsurface ocean hypothesis, and the Pluto/Kuiper Express to sample the outer reaches of the solar system. 2001Elsevier Science B.V. All rights reserved.

Both in yeast and humans, DNA polymerase (Pol) η functions in the error-free replication of UV-damaged DNA, and Polη has the unique ability to efficiently replicate through a cis-syn thymine–thymine (T–T) dimer by inserting two As opposite the two Ts of the dimer. Although human DINB1 -encoded Polκ belongs to the same protein family as Polη, Polκ shows no ability to bypass this DNA lesion and its biological function has remained unclear. Here, we examine Polκ for its ability to extend from primer-terminal mispairs opposite nondamaged and damaged DNA templates. We find that Polκ is a promiscuous extender of primer-terminal mispairs opposite nondamaged DNA templates, and interestingly, it is also very efficient at extending from a G opposite the 3′T of a T–T dimer. These observations provide biochemical evidence for a role of Polκ in the extension of mismatched base pairs during normal DNA replication, and in addition, they implicate Polκ in the mutagenic bypass of T–T dimers. In its proficient mismatch extension ability, Polκ is more similar to the unrelated DNA polymerase ζ than it is to the phylogenetically related Polη or Polι. Thus, in humans, Polκ would compete with Polζ for the extension of mismatched base pairs on damaged and undamaged DNAs.

Humans have three DNA polymerases, Poleta, Polkappa, and Poliota, which are able to promote replication through DNA lesions. However, the mechanism by which these DNA polymerases are targeted to the replication machinery stalled at a lesion site has remained unknown. Here, we provide evidence for the physical interaction of human Polkappa (hPolkappa) with proliferating cell nuclear antigen (PCNA) and show that PCNA, replication factor C (RFC), and replication protein A (RPA) act cooperatively to stimulate the DNA synthesis activity of hPolkappa. The processivity of hPolkappa, however, is not significantly increased in the presence of these protein factors. The efficiency (V(max)/K(m)) of correct nucleotide incorporation by hPolkappa is enhanced approximately 50- to 200-fold in the presence of PCNA, RFC, and RPA, and this increase in efficiency is achieved by a reduction in the apparent K(m) for the nucleotide. Although in the presence of these protein factors, the efficiency of the insertion of an A nucleotide opposite an abasic site is increased approximately 40-fold, this reaction still remains quite inefficient; thus, it is unlikely that hPolkappa would bypass an abasic site by inserting a nucleotide opposite the site.

This research explores the feasibility of web technology as a means for delivering building information to better support facility operations. Our research proposes just-in-time (JIT) facility documentation as a pragmatic solution to the limitations of current as-built documents, allowing more effective reuse of building information. Our investigation addresses four issues: (1) what building information is needed for facility operations; (2) how the design and construction team can improve the format for delivering the building information to facility operators; (3) how current web technology can store and deliver facility information in support of operations; and (4) what is the mechanism of documenting building information using the web technology. We surveyed literature, interviewed members of design and operations teams and reviewed current initiatives of industry and software vendors to identify problems with current practices. We also surveyed promising web technologies and conducted experiments to determine how these technologies could help to solve the problems. We constructed a conceptual framework of JIT facility documentation as a solution to current information fragmentation problems. We developed a prototype of the JIT document system to demonstrate a “proof of concept” by using current web technologies such as Autodesk's DWF, Microsoft's Active Server Pages, VB and Java script, and Access database to develop the prototype system. By dynamically composing HTML pages in response to task-specific requests, our prototype enables easy access and integration of a variety of building information to support facility operations.

Using laboratory data for the scattering of O by O2, CO and N2 pair potentials are constructed for O, C and N atoms. These potentials are then used to calculate collisional dissociation and energy transfer cross sections for O on O2, CO and N 2 , O 2 on O2, N on N2, and N2 on N2. Since the energetic ions often neutralize in the atmosphere corona, such cross sections are relevant to plasma ion bombardment of the atmospheres of Mars, Titan, Triton and Europa.

Magnetospheric and plasma science studies at Saturn offer a unique opportunity to explore in-depth two types of magnetospheres. These are an ‘induced’ magnetosphere generated by the interaction of Titan with the surrounding plasma flow and Saturn’s ‘intrinsic’ magnetosphere, the magnetic cavity Saturn’s planetary magnetic field creates inside the solar wind flow. These two objects will be explored using the most advanced and diverse package of instruments for the analysis of plasmas, energetic particles and fields ever flown to a planet. These instruments will make it possible to address and solve a series of key scientific questions concerning the interaction of these two magnetospheres with their environment.

Process analytical technology (PAT) and quality by design have gained importance in all areas of pharmaceutical development and manufacturing. One important method for monitoring of critical product attributes and process optimization in laboratory scale freeze-drying is manometric temperature measurement (MTM). A drawback of this innovative technology is that problems are encountered when processing high-concentrated amorphous materials, particularly protein formulations. In this study, a model solution of bovine serum albumin and sucrose was lyophilized at both conservative and aggressive primary drying conditions. Different temperature sensors were employed to monitor product temperatures. The residual moisture content at primary drying endpoints as indicated by temperature sensors and batch PAT methods was quantified from extracted sample vials. The data from temperature probes were then used to recalculate critical product parameters, and the results were compared with MTM data. The drying endpoints indicated by the temperature sensors were not suitable for endpoint indication, in contrast to the batch methods endpoints. The accuracy of MTM Pice data was found to be influenced by water reabsorption. Recalculation of Rp and Pice values based on data from temperature sensors and weighed vials was possible. Overall, extensive information about critical product parameters could be obtained using data from complementary PAT tools.

International audience; Sputtering of the Martian atmosphere by O+ pickup ions has been proposed as a potentially important process in the early evolution of the Martian atmosphere. In preparation for the MAVEN mission, we performed a study using a Monte Carlo model coupled to a molecular dynamic calculation to investigate the cascade sputtering effects in the region of the Martian exobase. Pickup ion fluxes based on test particle simulations in an MHD model for three different solar wind conditions are used to examine the local and global sputtering efficiencies. The resultant sputtering escape rate is 2 × 1024 s− 1 at nominal solar wind condition, and can be enhanced about 50 times when both the IMF strength and the solar wind pressure increase. It is found that when the IMF strength becomes stronger, both the pickup ion precipitation energies and the resultant sputtering efficiencies increase. The related escape flux, hot component, and atmospheric energy deposition deduced from the MAVEN measurements may reveal clues about the prominent enhanced sputtering effects. Significant hemispheric asymmetries can be observed related to the solar wind electric fields. The shielding by the crustal fields and the recycling onto the night-side due to different magnetic field draping features can also lead to regional variations of sputtering efficiencies. The results suggest that disturbed or enhanced solar wind conditions provide the best prospects for detecting sputtering effects for MAVEN mission.

DNA polymerase e (Pole) is a multi-subunit polymerase that contributes to genomic stability via its roles in leading strand replication and the repair of damaged DNA. Here we report the ternary structure of the Pole catalytic subunit (Pol2) bound to a nascent G:C base pair (Pol2G:C). Pol2G:C has a typical B-family polymerase fold and embraces the template-primer duplex with the palm, fingers, thumb and exonuclease domains. The overall arrangement of domains is similar to the structure of Pol2T:A reported recently, but there are notable differences in their polymerase and exonuclease active sites. In particular, we observe Ca2+ ions at both positions A and B in the polymerase active site and also observe a Ca2+ at position B of the exonuclease site. We find that the contacts to the nascent G:C base pair in the Pol2G:C structure are maintained in the Pol2T:A structure and reflect the comparable fidelity of Pol2 for nascent purine-pyrimidine and pyrimidine-purine base pairs. We note that unlike that of Pol3, the shape of the nascent base pair binding pocket in Pol2 is modulated from the major grove side by the presence of Tyr431. Together with Pol2T:A, our results provide a framework for understanding the structural basis of high fidelity DNA synthesis by Pol2.

Human DNA polymerase ι (hPolι) promotes translesion synthesis by inserting nucleotides opposite highly distorting or noninstructional DNA lesions. Here, we provide evidence for the physical interaction of hPolι with proliferating cell nuclear antigen (PCNA), and show that PCNA, together with replication factor C (RFC) and replication protein A (RPA), stimulates the DNA synthetic activity of hPolι. In the presence of these protein factors, on undamaged DNA, the efficiency ( V max / K m ) of correct nucleotide incorporation by hPolι is increased ≈80–150-fold, and this increase in efficiency results from a reduction in the apparent K m for the nucleotide. PCNA, RFC, and RPA also stimulate nucleotide incorporation opposite the 3′-T of the (6) thymine–thymine (T-T) photoproduct and opposite an abasic site. The interaction of hPolι with PCNA implies that the targeting of this polymerase to the replication machinery stalled at a lesion site is achieved via this association.

DNA polymerase eta (Poleta) functions in error-free bypass of ultraviolet light-induced DNA lesions, and mutational inactivation of Poleta in humans causes the cancer prone syndrome, the variant form of xeroderma pigmentosum (XPV). Both Saccharomyces cerevisiae and human Poleta efficiently insert two adenines opposite the two thymines of a cyclobutane pyrimidine dimer. Interestingly, in the fission yeast Schizosaccharomyces pombe, the eso1(+) encoded protein is comprised of two domains, wherein the NH(2) terminus is highly homologous to Poleta, and the COOH terminus is highly homologous to the S. cerevisiae Ctf7 protein which is essential for the establishment of sister chromatid cohesion during S phase. Here we characterize the DNA polymerase activity of S. pombe GST-Eso1 fusion protein and a truncated version containing only the Poleta domain. Both proteins exhibit a similar DNA polymerase activity with a low processivity, and steady-state kinetic analyses show that on undamaged DNA, both proteins misincorporate nucleotides with frequencies of approximately 10(-2) to 10(-3). We also examine the two proteins for their ability to replicate a cyclobutane pyrimidine dimer-containing DNA template and find that both proteins replicate through the lesion equally well. Thus, fusion with Ctf7 has no significant effect on the DNA replication or damage bypass properties of Poleta. The possible role of Ctf7 fusion with Poleta in the replication of Cohesin-bound DNA sequences is discussed.

DNA polymerase eta is unique among eukaryotic polymerases in its proficient ability to replicate through a variety of distorting DNA lesions. We report here the crystal structure of the catalytic core of S. cerevisiae DNA polymerase eta, determined at 2.25A resolution. The structure reveals a novel polydactyl right hand-shaped molecule with a unique polymerase-associated domain. We identify the catalytic residues and show that the fingers and thumb domains are unusually small and stubby. In particular, the unexpected absence of helices "O" and "O1" in the fingers domain suggests that openness of the active site is the critical feature which enables DNA polymerase eta to replicate through DNA lesions such as a UV-induced cis-syn thymine-thymine dimer.

DNA polymerase η (Polη) functions in the error-free bypass of UV-induced DNA lesions, and a defect in Polη in humans causes the cancer-prone syndrome, the variant form of xeroderma pigmentosum. Both yeast and human Polη replicate through a cis-syn thymine-thymine dimer (TT dimer) by inserting two As opposite the two Ts of the dimer. Polη, however, is a low-fidelity enzyme, and it misinserts nucleotides with a frequency of ≈ 10 −2 to 10 −3 opposite the two Ts of the TT dimer as well as opposite the undamaged template bases. This low fidelity of nucleotide insertion seems to conflict with the role of Polη in the error-free bypass of UV lesions. To resolve this issue, we have examined the ability of human and yeast Polη to extend from paired and mispaired primer termini opposite a TT dimer by using steady-state kinetic assays. We find that Polη extends from mispaired primer termini on damaged and undamaged DNAs with a frequency of ≈ 10 −2 to 10 −3 relative to paired primer termini. Thus, after the incorporation of an incorrect nucleotide, Polη would dissociate from the DNA rather than extend from the mispair. The resulting primer-terminal mispair then could be subject to proofreading by a 3′→5′ exonuclease. Replication through a TT dimer by Polη then would be more accurate than that predicted from the fidelity of nucleotide incorporation alone.

The dependence of the sputtering yield on the incident angle, Θ, is determined using molecular dynamics (MD) simulations for a cylindrical track produced by a fast ion. For a `small' spike radius and for the mean energy in the track, Eexc, smaller than the binding energy, U, a (cosΘ)−1.7 dependence is found, close to the linear collision cascade (LCC) result and to some thermal spike models. On the other hand, when Eexc>U, the incident angle dependence is (cosΘ)−1. For a larger spike radius we obtain a ∼(cosΘ)−1.6 dependence for both high and low energy densities. Analytic spike models based on diffusive transport are shown not to give satisfactory results. In addition, at low energy densities we see correlated atom ejection ignored in analytic models. Applying the MD results to the experimental data for electronic sputtering of solid O2 at large excitation densities suggests that the effective spike radius is larger than the initial Bohr adiabatic radius indicating that energy is rapidly transported from the initially narrow track.

Monte Carlo models are used to describe the interaction between the incident pick-up ions and the Mars neutral atmosphere. The sputtered population inside the corona and escaping particles are described using a modified 3D test particle model, whereas, the heating effect due to the incident flux is described using a 2D Direct Simulation Monte Carlo. These results show that the standard 1D models overestimate the sputtering yield (by 15–25%), when corrected for coronal ejection. It is also shown that the exobase altitude can depend on sputtering. Two epochs of Mars history are simulated. For an epoch suggested to be about 2.5 Gyr ago, sputtering is at least as important as dissociative-recombination for populating the corona and the heating due to the pick-up ion flux is of the same order as the EUV and UV heating of the thermosphere. For this epoch and present solar minimum conditions we present the distribution in the density and the energy of the sputtered particles in Mars corona. In particular we show that the polar and dusk regions are the most dense regions and the shadow of the dawn and polar regions the most energetic regions.

An extension of the analytical model for vertical continuous casting of bars previously developed by the authors (Johnson and Cherukuri. Proc. Roy. Soc. London A 455 (1999) 227) is presented. The new features include temperature dependence of thermal conductivity and the constitutive equations. The model can be used to readily predict the effect of various process parameters such as cooling conditions, liquid pool pressure, casting speed on the solidification process. Consequently, it can be readily implemented in a control system to adjust the process parameters of a typical solidification process. In addition, it can also be used as a guide to gain insight into the nature of the solution prior to conducting more general and expensive finite element simulations.

Elastic scattering cross sections have been calculated for the O(3P)+O(3P) collision at energies E=1–10 eV using exact quantum calculations and the semiclassical Jeffries–Wentzel–Kramers–Brillouin approximation with the full set of 18 states of O2 which separate to this system. These cross sections are required for calculating escape probability from planetary atmospheres. In addition, an average potential has been calculated and compared to popularly used potential energy forms. The average potential has also been used to generate the cross sections in this energy range. Escape depths for E=1 and 10 eV have been calculated to be 1.0×1015 and 2.5×1014/cm2, respectively.

Abasic (AP) sites are one of the most frequently formed lesions in DNA, and they present a strong block to continued synthesis by the replicative DNA machinery. Here we show efficient bypass of an AP site by the combined action of yeast DNA polymerases δ and ζ. In this reaction, Polδ inserts an A nucleotide opposite the AP site, and Polζ subsequently extends from the inserted nucleotide. Consistent with these observations, sequence analyses of mutations in the yeastCAN1s gene indicate that A is the nucleotide inserted most often opposite AP sites. The nucleotides C, G, and T are also incorporated, but much less frequently. Enzymes such as Rev1 and Polη may contribute to the insertion of these other nucleotides; the predominant role of Rev1 in AP bypass, however, is likely to be structural. Steady-state kinetic analyses show that Polζ is highly inefficient in incorporating nucleotides opposite the AP site, but it efficiently extends from nucleotides, particularly an A, inserted opposite this lesion. Thus, in eukaryotes, bypass of an AP site requires the sequential action of two DNA polymerases, wherein the extension step depends solely upon Polζ, but the insertion step can be quite varied, involving not only the predominant action of the replicative DNA polymerase, Polδ, but also the less prominent role of various translesion synthesis polymerases.

The heavy ion plasma and energetic particles continuously sputter the surfaces of the icy satellites embedded in the inner Saturnian magnetosphere. We evaluate satellite sputtering and compare the resulting H2O source distribution with the source distribution expected for the OH cloud recently observed by Hubble Space Telescope. At each satellite we combine, for the 2rst time, the data from the Plasma Science (PLS) and Low Energy Charged-Particle (LECP) instruments from Voyager 1 and 2, unifying them into a single plasma distribution function. Based on the calculated satellite sources, we conclude that sputtering of the satellite surfaces cannot produce the observed OH cloud and that a large additional source in the inner magnetosphere is needed to fully explain the HST observations. c

Energetic electrons trapped in Jupiter's magnetic field are a principal source of energy for driving chemistry on the surface of Europa. Here we show that energetic (10 keV-10 MeV) electrons precipitate primarily on the trailing hemisphere, and we give the spatial distribution of the dose-rate deposited in Europa's surface. Based on this we propose that energetic electrons are a primary agent in determining the hemispherical differences in Europa's albedo, which have been attributed to differences in the incident ion flux. We compare the spatial distribution in the dose-rate deposited by the energetic electrons to the spatial distribution in the hydrate (likely frozen, hydrated sulfuric acid) determined by Galileo's near-infrared mapping spectrometer. This comparison supports the idea that radiolysis by the energetic electrons contributes significantly to producing the hydrate.

Recent Hubble Space Telescope (HST) observations of the densities of neutralOH molecules that coexist with and are precursors of the plasma ions have constrained models for the plasma sources. An orbital simulation model of the evolution of H2O molecules emitted from the satellites and the E ring is employed to put additional constraints on the possible plasma/neutral sources in Saturn's magnetosphere. We find that a large H2O source concentrated near the orbit of Enceladus (of the order 1027 H2O molecules/s) is needed to account for the observed OH neutral cloud. We suggest that a large amount of optically unobserved material near Enceladus could provide the “missing” H2O source. A Monte-Carlo collisional transport code for sputtering of ice surfaces is developed and applied to the E-ring grains. Grain lifetimes are found to be short (∼50 years for 1-μm grains and only a few years for 0.1-μm grains), so grains must be resupplied regularly to keep the E ring in the present state. Orbital collisions between icy fragments, possibly remains of a disrupted satellite near Enceladus, are the suggested mechanism for replenishing the E ring.

Galileo Orbiter measurements of energetic ions (20 keV to 100 MeV) and electrons (20-700 keV) in Jupiter's magnetosphere are used, in conjunction with the JPL electron model (less than 40 MeV), to compute irradiation effects in the surface layers of Europa, Ganymede, and Callisto. Significant elemental modifications are produced on unshielded surfaces to approximately centimeter depths in times of less than or equal to 10(exp 6) years, whereas micrometer depths on Europa are fully processed in approximately 10 years. Most observations of surface composition are limited to optical depths of approximately 1 mm, which are indirect contact with the space environment. Incident flux modeling includes Stormer deflection by the Ganymede dipole magnetic field, likely variable over that satellite's irradiation history. Delivered energy flux of approximately 8 x 10(exp 10) keV/square cm-s at Europa is comparable to total internal heat flux in the same units from tidal and radiogenic sources, while exceeding that for solar UV energies (greater than 6 eV) relevant to ice chemistry. Particle energy fluxes to Ganymede's equator and Callisto are similar at approximately 2-3 x 10(exp 8) keV/square cm-s with 5 x 10(exp 9) at Ganymede's polar cap, the latter being comparable to radiogenic energy input. Rates of change in optical reflectance and molecular composition on Europa, and on Ganymede's polar cap, are strongly driven by energy from irradiation, even in relatively young regions. Irradiation of nonice materials can produce SO2 and CO2, detected on Callisto and Europa, and simple to complex hydrocarbons. Iogenic neutral atoms and meteoroids deliver negligible energy approximately 10(exp 4-5) keV/square cm-s but impacts of the latter are important for burial or removal of irradiation products. Downward transport of radiation produced oxidants and hydrocarbons could deliver significant chemical energy into the satellite interiors for astrobiological evolution in putative sub-surface oceans.

The bombardment of the surface of Europa by charged particles trapped in the jovian magnetosphere causes sputtering and decomposition of surface materials leading to the production of a tenuous 02 atmosphere. In this paper we use a direct Monte Carlo simulation of the atmosphere and we account for adsorption, thermalization and re-emission of condensed 02, dissociation and ionization by magnetospheric electron and photon impact, and collisional ejection by the low energy plasma in the magnetosphere. Since the ion flux to the surface and the O2 production are not well constrained, we treat the surface source as a variable parameter. To account for the production of atomic O seen by HST (Hall et al., 1995, 1998), we find that larger surface fluxes are required than those predicted (Cooper et al., 2001). This is due primarily to the inclusion of photo-dissociation which leads to loss. The variation of atmospheric 02 and O from near equilibrium near the surface to highly non-equilibrium is shown and is poorly approximated by the escape atmosphere assumed by Saur et al. (1998). © 2001 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Dissociation and dissociative ionization of molecular nitrogen by solar UV radiation and by photoelectrons and sputtering by magnetospheric ions are the main sources of translationally excited (hot) nitrogen atoms and molecules in the upper atmosphere of Titan. The Boltzmann equations describing the production, thermalization, and transport of suprathermal nitrogen atoms and molecules in Titan's upper atmosphere were solved using the Direct Simulation Monte Carlo method. Steady-state energy distribution functions for the hot nitrogen atoms and molecules were calculated vs. altitude in the thermosphere-exosphere transition region. The contribution of dissociation and atmospheric sputtering to the formation of Titan's hot nitrogen corona and to the escape flux into the Saturnian magnetosphere are described using the calculated energy distribution functions. It is shown that photo-dissociation dominates and, therefore, the principal ejecta are N atoms.

DNA polymerase eta (Poleta) functions in error-free replication of UV-damaged DNA, and in vitro it efficiently bypasses a cis-syn T-T dimer by incorporating two adenines opposite the lesion. Steady state kinetic studies have shown that both yeast and human Poleta are low-fidelity enzymes, and they misincorporate nucleotides with a frequency of 10(-2)-10(-3) on both undamaged and T-T dimer-containing DNA templates. To better understand the role of Poleta in error-free translesion DNA synthesis, here we examine the ability of Poleta to extend from base mismatches. We find that both yeast and human Poleta extend from mismatched base pairs with a frequency of approximately 10(-3) relative to matched base pairs. In the absence of efficient extension of mismatched primer termini, the ensuing dissociation of Poleta from DNA may favor the excision of mismatched nucleotides by a proofreading exonuclease. Thus, we expect DNA synthesis by Poleta to be more accurate than that predicted from the fidelity of nucleotide incorporation alone.

A goal of Cassini’s extended mission is to examine the seasonal variations of Saturn’s magnetosphere, moons, and rings. Recently we showed that the thermal plasma between the main rings and Enceladus exhibited a time dependence that we attributed to a seasonally variable source of oxygen from the main rings (Elrod, M.K., Tseng, W.-L., Wilson, R.J., Johnson, R.E. [2012]. J. Geophys. Res. 117, A03207. http://dx.doi.org/10.1029/2011JA017332 ). Such a temporal variation was subsequently seen in the energetic ion composition (Christon, S.P., Hamilton, D.C., DiFabio, R.D., Mitchel, D.G., Krimigis, S.M., Jontof-Hutter, D.S. [2013]. J. Geophys. Res. 28. http://dx.doi.org/10.1002/jgra.50383 ; Christon, S.P., Hamilton, D.C., Mitchell, D.G., DiFabio, R.D., Krimigis, S.M. [2014]. J. Geophys. Res., submitted for publication). Here we incorporate the most recent measurements by the Cassini Plasma Spectrometer (CAPS) into our earlier analysis (Elrod, M.K., Tseng, W.-L., Wilson, R.J., Johnson, R.E. [2012]. J. Geophys. Res. 117, A03207. http://dx.doi.org/10.1029/2011JA017332 ) and our modeling (Tseng, W.-L., Johnson, R.E., Elrod, M.K. [2013a]. Planet. Space Sci. 77, 126–135) of the thermal plasma in the region between the main rings and the orbit of Enceladus. Data taken in 2012, well past equinox for which the northern side of the main rings were illuminated, appear consistent with a seasonal variation. Although the thermal plasma in this region comes from two sources that have very different radial and temporal trends, the extended ring atmosphere and the Enceladus torus, the heavy ion density is found to exhibit a steep radial dependence that is similar for the years examined. Using our chemical model, we show that this dependence requires either a radial dependence for Enceladus torus that differs significantly from recent models or, as we suggest here, enhanced heavy ion quenching/neutralization with decreasing distance from the edge of the main rings. We examine the possible physical processes and suggest that the presence of small grains and the precipitation of the inward diffusing high-energy background radiation onto the edge of the main rings play important roles.

Urine ligase chain reaction (LCR) and PCR tests and urethral swab culture were compared for their abilities to detect Chlamydia trachomatis infection in 3,639 asymptomatic men by using one-, two-, and three-test reference standards. Frozen urine at four of five participating centers was also tested by a transcription-mediated amplification assay which was used as a reference test. LCR increased the yield of positive results by 27% and PCR increased the yield of positive results by 26% over the yield of positive results by culture ( n = 295). LCR and PCR sensitivities were similar, ranging from 80.4 to 93.5%, depending on the reference standard. Culture sensitivity was substantially less. A multiple-test standard yielded LCR, PCR, and culture specificities of 99.6%, with or without discrepant analysis. Test performance varied among centers partly due to different interpretations of the testing protocols. The study confirms that urine LCR and PCR for the detection of C. trachomatis have substantially improved sensitivities over that of urethral swab culture for testing of asymptomatic men, enabling screening of this important target group. These tests, perhaps in combination, are also candidate reference tests for the conduct of test evaluation studies.

Central nervous system (CNS) and spinal cord tumors are not uncommon in patients with neurofibromatosis (NF); however, it is impossible to select patients with NF who are at a particularly high risk. Localized pruritus may be a clue to the presence of a spinal cord or CNS tumor. This is the first report of an infant with features of NF, whose presenting symptom of a spinal cord tumor was localized symmetrical dermatomal itch. Moreover, we review the literature of localized pruritus in CNS and spinal cord tumors and peripheral nervous system conditions. (J Am Acad Dermatol 2000;43:958-61.)

Background: The relative emphasis that major medical journals give to topic areas has a potential effect on priorities in patient care, policy decisions, and public awareness. We measured the distribution of topics in two journals, by disease categories and domains, over a calendar year. Methods: All original investigations, reviews, editorials, and special articles published in 1998 by the Journal of the American Medical Association and the New England Journal of Medicine were classified by article type, disease category, and domain. The 12 domains ranged from basic science to health policy, and included primary and secondary prevention. Results: The 1159 articles published in 1998 included 889 (77%) articles about specific diseases—590 falling within eight specialties—and 190 (16%) articles on generic topics. Eighty (7%) articles concerned the behaviors that cause disease. Primary prevention and screening were the subject of 71 (6%) and 29 (3%) articles, respectively. Most of these concerned uncommon issues in patient care. Although 27 (2%) articles dealt with essential health promotion (e.g., diet, exercise), and none included a study on how to help patients to exercise, stop smoking, or eat a healthy diet. In contrast, 451 (39%) articles concerned the diagnosis and treatment of patients with disease. Conclusions: The relative emphasis that journals gave to prevention during the sample period seems discordant with its importance to patients and public health. Potential explanations include poor volume and quality of submitted research and editorial concerns about importance and reader appeal.

The human DINB1 gene shares a high degree of homology with the Escherichia coli dinB gene. Here, we purify the hDINB1- encoded protein and show that it is a DNA polymerase. Because hDinB1 is the eighth eukaryotic DNA polymerase to be described, we have named it DNA polymerase (Pol) θ. hPolθ is unable to bypass a cis-syn thymine–thymine dimer, nor does it bypass a (6–4) photoproduct or an abasic site. We also examine the fidelity of hPolθ on nondamaged DNA templates by steady-state kinetic analyses and find that hPolθ misincorporates deoxynucleotides with a frequency of about 10 −3 to 10 −4 . We discuss the relationship between the fidelity of hPolθ and its inability to bypass DNA damage.

The bombardment of low temperature condensed gas solids by MeV light ions produces electronic excitations that can decay non-radiatively, transferring kinetic energy to the lattice and causing ejection (sputtering) of atoms. The experimental data for the sputtering yield Y of solid O 2 and N 2 over a range of dE/dx are proportional to (dE/dx)2, where dE/dx is the energy deposited per unit path length. Parametrizing an analytical thermal spike model with constant track radius gave satisfactory agreement with the data [Johnson et al., Phys. Rev. B 44, (1991) 14]. However, molecular dynamics calculations for solid O 2 indicate that Y is proportional to dE/dx at high dE/dx for constant track radius and that the energy transport processes diVer from those assumed in spike models. Here we propose that the quadratic dependence in the experimental data is due to a track radius that increases with dE/dx, opposite to the dependence predicted by the Bohr adiabatic radius. This radius is determined by fast energy transport processes prior to the principal energy release due to lattice motion: e.g. by hole repulsion and diVusion, by cooling electrons, or by excitation transport. Energy transport for a vibrationally excited track was examined, and it was found that sputtering was ineYcient for vibrational excitation of solid O 2 . © 2000 Elsevier Science B.V. All rights reserved.

Bombarding a solid with fast ions can give atoms within a localized region enough kinetic energy to escape from the material. Thermal spike models have been used to explain this process for metals, insulators and condensed gas solids. Here we use molecular dynamics (MD) simulations of a cylindrical spike to examine the effect of material stiffness and surface boundary conditions on the spike calculations of the yield. When loss from the surface of the material is suppressed, the dependence of the yield on the effective stopping power, (d E /d x ) eff , is roughly quadratic at high (d E /d x ) eff as in most spike calculations. If escape is allowed, rather than reducing the surface temperature and the yield, both the temperature and the yield increase dramatically and the yield exhibits the roughly linear dependence reported earlier for full MD calculations at high (d E /d x ) eff and constant track radius. This change in dependence is determined by the radial pressure pulse and the energy flow to the surface. By changing a parameter in the interaction potential the stiffness of the material in the MD simulations is varied which changes the effect of the pressure pulse. Not surprisingly, for very stiff materials the yield cannot be related to the spike model but more closely resembles spallation.

The Saccharomyces cerevisiae RAD30 gene functions in error-free replication of UV-damaged DNA. RAD30 encodes a DNA polymerase, Pol η, which inserts two adenines opposite the two thymines of a cis-syn thymine–thymine (T–T) dimer. Here we use steady-state kinetics to determine the accuracy of DNA synthesis opposite the T–T dimer. Surprisingly, the accuracy of DNA synthesis opposite the damaged DNA is nearly indistinguishable from that opposite nondamaged DNA, with frequencies of misincorporation of about 10−2 to 10−3. These studies support the hypothesis that unlike most DNA polymerases, Pol η is able to tolerate distortions in DNA resulting from damage, which then enables the polymerase to utilize the intrinsic base pairing ability of the T–T dimer.

Xeroderma pigmentosum (XP) patients are highly sensitive to sunlight, and they suffer from a high incidence of skin cancers. The variant form of XP results from mutations in the hRAD30A gene, which encodes the DNA polymerase in humans, hPol(eta). Of the eukaryotic DNA polymerases, only human Pol(eta) and its yeast counterpart have the ability to replicate DNA containing a cis-syn thymine-thymine (T-T) dimer. Here we measure the fidelity of hPol(eta) on all four nondamaged template bases and at each thymine residue of a cis-syn T-T dimer. Opposite all four nondamaged template bases, hPol(eta) misincorporates nucleotides with a frequency of approximately 10(-2)-10(-3), and importantly, hPol(eta) synthesizes DNA opposite the T-T dimer with the same accuracy and efficiency as opposite the nondamaged DNA. The low fidelity of hPol(eta) may derive from a flexible active site that renders the enzyme more tolerant of geometric distortions in DNA and enables it to synthesize DNA past a T-T dimer.

Abasic (AP) sites arise in DNA at a substantial rate by spontaneous hydrolysis of the N-glycosylic bond, and it has been estimated that as many as 104 purines are lost spontaneously in a human cell per day (27). AP sites are also formed in DNA as intermediates in base excision repair (BER), which removes damaged bases formed by oxidation and alkylation. The first step of BER involves the action of a DNA glycosylase which catalyzes the hydrolysis of the N-glycosylic bond linking the damaged base to the deoxyribose phosphate backbone. The ensuing AP site is recognized by a class II AP endonuclease which cleaves the phosphodiester backbone on the 5′ side of the AP site, leaving a 3′-hydroxyl group and a 5′-baseless deoxyribose 5′-phosphate residue. Removal of the deoxyribose 5′-phosphate residue, followed by DNA repair synthesis and ligation, completes the repair process (6, 39, 45). Two class II AP endonucleases, Apn1 and Apn2, have been identified in the yeast Saccharomyces cerevisiae. Apn1 represents the major AP endonuclease activity in yeast, and it shares extensive homology with Escherichia coli endonuclease IV (31, 32). Apn2 is an homolog of E. coli exonuclease III and of human HAP1 (REF1) AP endonuclease (3, 23). Genetic and biochemical studies have indicated that Apn1 and Apn2 constitute alternate pathways for the removal of AP sites in yeast (23). In contrast to BER, which removes damaged bases which do not perturb the helical structure of DNA, nucleotide excision repair (NER) removes DNA damages that cause significant distortion of the helix (36). For example, NER removes cyclobutane pyrimidine dimers and (6-4) photoproducts formed by ultraviolet light and is also involved in the removal of intrastrand and interstrand cross-links and bulky adducts formed in DNA upon treatment with a variety of chemical agents. NER is a highly conserved process among eukaryotes from yeast to humans (36). In S. cerevisiae, NER is accomplished via the concerted action of the following: Rad14, RPA, the Rad4-Rad23 complex, and the Rad7-Rad16 complex, all of which function in DNA damage recognition (5, 11, 12, 14–16, 22); TFIIH, which contains the Rad3 and Rad25 DNA helicases, essential for DNA unwinding (41); and the Rad1-Rad10 and Rad2 nucleases (18, 42, 43) which incise the damaged strand on the 5′ and 3′ sides of the lesion, respectively (2, 17). Both in yeast and humans, dual incision by the NER ensemble results in the release of an oligonucleotide fragment ∼25 to 30 nucleotides long (10, 28, 29). In humans, a defect in NER results in xeroderma pigmentosum (XP). XP individuals are extremely sensitive to sunlight, and the frequencies of basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin are increased 1,000-fold or more in these patients (24, 25). XP patients also manifest an increase in the incidence of cancers in sites not exposed to UV radiation, and there is a disproportionate increase in the frequency of malignant neoplasms of the brain and other parts of the central nervous system and extraglossal oral cavity in these individuals (24, 25). These observations have suggested the involvement of NER in the removal of non-UV-related DNA damage. Because AP sites are formed so frequently in mammalian cells, here we utilize the yeast system to examine the role of NER in the removal of AP sites in eukaryotes. Our studies indicate that Apn1, Apn2, and NER constitute alternate competing pathways for the removal of AP sites in yeast.

The discovery of water vapour and ice particles erupting from Saturn's moon Enceladus fuelled speculation that an internal ocean was the source. Alternatively, the source might be ice warmed, melted or crushed by tectonic motions. Sodium chloride (that is, salt) is expected to be present in a long-lived ocean in contact with a rocky core. Here we report a ground-based spectroscopic search for atomic sodium near Enceladus that places an upper limit on the mixing ratio in the vapour plumes orders of magnitude below the expected ocean salinity. The low sodium content of escaping vapour, together with the small fraction of salt-bearing particles, argues against a situation in which a near-surface geyser is fuelled by a salty ocean through cracks in the crust. The lack of observable sodium in the vapour is consistent with a wide variety of alternative eruption sources, including a deep ocean6, a freshwater reservoir, or ice. The existing data may be insufficient to distinguish between these hypotheses.

The SGS1 gene of the yeast Saccharomyces cerevisiae encodes a DNA helicase with homology to the human Bloom's syndrome gene BLM and the Werner's syndrome gene WRN . The SRS2 gene of yeast also encodes a DNA helicase. Simultaneous deletion of SGS1 and SRS2 is lethal in yeast. Here, using a conditional mutation of SGS1 , it is shown that DNA replication and RNA polymerase I transcription are drastically inhibited in the srs2 Δ sgs1-ts strain at the restrictive temperature. Thus, SGS1 and SRS2 function in DNA replication and RNA polymerase I transcription. These functions may contribute to the various defects observed in Werner's and Bloom's syndromes.