bluuebunny/crossref_metadata_2025 huggingface dataset:
The cohesive energetics of solid cesium chloride
Authors: Pyper N. C.
Published: January 2003

The cohesive energetics of the sixfold and eightfold coordinated phases of solid cubic cesium chloride are studied using a nonempirical fully ionic description. The Oxford Dirac–Fock program is used to compute the ion wave functions and rearrangement energies needed to convert a free anion into the compressed yet still spherically symmetric anions optimally adapted to crystal. The Relativistic Integrals Program (RIP) is used to compute uncorrelated two-body interionic interaction potentials which take full account of relativity and are exact for given ion wave functions. These potentials and the further contributions arising from electron correlation are reported. The OEMFS model for describing the environment of the anion in-crystal yields lattice energies and equilibrium interionic separations in good agreement with experiment and correctly predicts the eight-fold coordinated structure to lie lowest in energy. The “optimal” anion–anion short-range potentials, computed by using at each geometry the wave function optimal for that geometry, are compared with the “frozen” potential in which the same anion wave function is used to compute the entire potential. The “frozen” anion–anion potential in solid sodium chloride is reported. The basic idea in the ab initio perturbed ion (AIPI) method, that the wave functions of anions in-crystal remain spherically symmetric yet as strongly orthogonal as possible to those of neighboring ions, cannot be justified. It differs from the standard view in the RIP computations that an ion wave function only remains spherically symmetric whilst overlapping with those of neighboring ions, such overlaps generating the short-range interionic repulsions. The RIP predictions of crystal cohesive energetics are preferable to those of the AIPI method. The correlation energy used in AIPI calculations is theoretically objectionable for crystals and is numerically poor. For CsCl, the anion wave function, rearrangement energy, and closest cation–anion repulsion optimal for the 8:8 structure at each geometry are all essentially identical to their counterparts in the 6:6 phase. The different coordination numbers in the two phases render unequal the effective cation–anion interactions given as the sum of the true cation–anion potentials and a fraction of the rearrangement energy. This inequality removes RIP computations from that class of theories which fail to predict the correct energy ordering of the phases through using the same effective potential in both structures.
Oxygen isotopic fractionation during UV and visible light photodissociation of ozone
Authors: Chakraborty Subrata , Bhattacharya S. K.
Published: January 2003

Stratospheric ozone is essentially in a steady state due to the simultaneous formation and dissociation and found to be enriched (mass-independently) in heavy oxygen isotopes. Though there have been a number of experimental and theoretical studies on the mechanism(s) associated with the formation of isotopically heavy ozone, the decomposition processes were not studied in necessary detail. Here we report a novel feature in the isotopic fractionation of ozone during photodissociation in the UV and visible wavelengths. Photodissociation of ozone produces isotopically light oxygen, enriching the leftover ozone pool. Interestingly, the isotopic fractionation patterns are not similar in the two wavelength regions. Dissociation at visible wavelengths displays a mass-dependent slope (Δδ17O/Δδ18O=0.54) whereas UV dissociation shows a mass-independent character (Δδ17O/Δδ18O=0.63). O3 photodissociation in UV wavelengths is normally associated with another effective channel of dissociation, i.e., O3+O(1D). It is demonstrated for the first time that pure UV photodissociation of ozone [i.e., without the O(1D) channel] gives a slope of unity intriguingly similar to that obtained in the ozone formation process. A combination of the two processes i.e., mass dependent O(1D)+O3 reaction and pure UV photodissociation is responsible for the observed slope of 0.63.
Gradient-free and gradient-dependent approximations in the total energy bifunctional for weakly overlapping electron densities
Authors: Wesolowski Tomasz A. , Tran Fabien
Published: January 2003

We analyze the performance of gradient-free local density approximation (LDA) and gradient-dependent generalized gradient approximation (GGA) functionals in a density functional theory variational calculations based on the total energy bifunctional (E[ρ1,ρ2]). These approximations are applied to the exchange-correlation energy and to the nonadditive component of the kinetic energy of the complex. Benchmark ab initio interaction energies taken from the literature for 25 intermolecular complexes for which the interaction energies fall into the 0.1–3.0 kcal/mol range are used as reference. At the GGA level, the interaction energies derived from E[ρ1,ρ2] are more accurate than the Kohn–Sham ones. LDA leads to very good interaction energies for such complexes where the ρ1,ρ2 overlap is very small (Ne-Ne, Ar-Ar, for instance) but it is not satisfactory for such cases where the overlap is larger. Introduction of gradient-dependent terms into the approximate part of E[ρ1,ρ2] improves significantly the overall accuracy of the interaction energies. Gradient-dependent functionals applied in E[ρ1,ρ2] lead to the average error and the average absolute error of the interaction energies amounting to 0.08 kcal/mol and 0.29 kcal/mol, respectively.
Perimeter effect in very small ferroelectrics
Authors: Dawber Matthew , Jung Dong Jin , Scott James F.
Published: January 2003

We conducted impedance spectroscopy measurements on lead zirconate titanate capacitors of varying lateral size from 130×180 μm down to 1×1 μm. We discovered a peak in the impedance response with a frequency that depends on the perimeter of the capacitor with an exponential relationship. Our model for this effect is based on the idea that at low fields, nucleation occurs at stress free areas (in our case, the capacitor perimeter) and that domain-wall motion is restricted by viscous drag caused by the coupling of the domain wall to acoustic phonons. The relaxation time for the impedance peak is the time for the domain walls to propagate from the perimeter to the center. This process is somewhat different from the normal switching response; it occurs for small fields, when the capacitor has not been prepoled. The mechanism is similar to that for relaxation of an unstable polarization state. This model can also explain the logarithmic time dependence sometimes observed in those studies.
Operating characteristics of a semiconducting polymer laser pumped by a microchip laser
Authors: Turnbull G. A. , Andrew P. , Barnes W. L. , Samuel I. D. W.
Published: January 2003

We report the demonstration of a compact, all-solid-state polymer laser system featuring a microchip laser as the pump source. The laser was configured as a surface-emitting, two-dimensional distributed feedback laser, based on the conjugated polymer poly(2-methoxy-5-(2′-ethylhexyloxy)-1,4-phenylene vinylene). Pulsed, band-edge lasing was observed at 636 nm above a threshold pump energy of 4 nJ. The laser exhibited an energy slope efficiency of 6.8%, with a maximum output energy of 1.12 nJ at a pump energy of 20.4 nJ. The output beam had an azimuthally polarized annular profile with a beam quality factor (M2) of 2.2, close to the theoretical value of the lowest-order Laguerre–Gaussian and Bessel–Gaussian annular modes. We explain the origin of the azimuthal polarization as due to a coherent combination of the resonant fields supported by the two gratings.
Gold Schottky contacts on oxygen plasma-treated, n-type ZnO(0001̄)
Authors: Coppa B. J. , Davis R. F. , Nemanich R. J.
Published: January 2003

Reverse bias current–voltage measurements of ∼100-μm-diameter gold Schottky contacts deposited on as-received, n-type ZnO(0001̄) wafers and those exposed for 30 min to a remote 20% O2/80% He plasma at 525±20 °C and cooled either in vacuum from 425 °C or the unignited plasma gas have been determined. Plasma cleaning resulted in highly ordered, stoichiometric, and smooth surfaces. Contacts on as-received material showed μA leakage currents and ideality factors >2. Contacts on plasma-cleaned wafers cooled in vacuum showed ∼36±1 nA leakage current to −4 V, a barrier height of 0.67±0.05 eV, and an ideality factor of 1.86±0.05. Cooling in the unignited plasma gas coupled with a 30 s exposure to the plasma at room temperature resulted in decreases in these parameters to ∼20 pA to −7 V, 0.60±0.05 eV, and 1.03±0.05, respectively. Differences in the measured and theoretical barrier heights indicate interface states. (0001) and (0001̄) are used in this letter to designate the polar zinc- and oxygen-terminated surfaces, respectively.
Oblique ion texturing of yttria-stabilized zirconia: the {211}〈111〉 structure
Authors: Berdahl Paul , Reade Ronald P. , Liu Jinping , Russo Richard E. , Fritzemeier Les , Buczek David , Schoop Urs
Published: January 2003

Amorphous (Zr,Y)Ox films were synthesized by reactive magnetron sputtering and subsequently crystallized by oblique ion bombardment. Crystalline texture nucleated by the ion beam was replicated by solid-phase epitaxial growth throughout the formerly amorphous yttria-stabilized zirconia (YSZ) film. The resulting YSZ films have (211) orientation normal to the substrate with in-plane directions (111), parallel, and (110), transverse, to the azimuth of the ion beam. We hypothesize that the texture mechanism involves ion-induced film compression and shear. The results, taken together with prior work, show that oblique ion texturing of amorphous films is a general phenomenon that can be used to fabricate substrates with more than one type of crystallographic orientation.
Phosphorescent top-emitting organic light-emitting devices with improved light outcoupling
Authors: Riel H. , Karg S. , Beierlein T. , Ruhstaller B. , Rieß W.
Published: January 2003

A dielectric capping layer has been used to increase the light output and to tune the spectral characteristics of top-emitting, phosphorescent organic light-emitting devices (OLEDs). By controlling the thickness of the dielectric layer deposited on top of a thin metal cathode, the transmittance of the top electrode can be adjusted. Maximum light output is not achieved at highest cathode transmittance, indicating that the interplay between different interference effects can be controlled by means of the capping-layer thickness. Furthermore, we demonstrate that the electrical device characteristic is not influenced by the capping layer. The strength of our concept in particular lies in the fact that the optical and the electrical device performance can be optimized separately. Using the capping-layer concept, we have achieved an OLED efficiency of 64 cd/A with pure green emission.
Magneto-optical light scattering from ferromagnetic surfaces
Authors: González M. U. , Armelles G. , Martı́nez Boubeta C. , Cebollada A.
Published: January 2003

We have studied the optical and magneto-optical components of the light scattered by the surface of several Fe films with different morphologies. We present a method, based on the ratio between the optical and magneto-optical components of the scattered intensity, to discern the physical origin, either structural or magnetic corrugation, of the light scattered by these ferromagnetic surfaces. Surface versus bulk magnetic information can be separated by magneto-optical light scattering measurements, the scattered light being more sensitive to magnetization differences between surface and bulk than the reflected one.
Formation of dispersions using “flow focusing” in microchannels
Authors: Anna Shelley L. , Bontoux Nathalie , Stone Howard A.
Published: January 2003

A flow-focusing geometry is integrated into a microfluidic device and used to study drop formation in liquid–liquid systems. A phase diagram illustrating the drop size as a function of flow rates and flow rate ratios of the two liquids includes one regime where drop size is comparable to orifice width and a second regime where drop size is dictated by the diameter of a thin “focused” thread, so drops much smaller than the orifice are formed. Both monodisperse and polydisperse emulsions can be produced.
Charging effects in silicon nanocrystals within SiO2 layers, fabricated by chemical vapor deposition, oxidation, and annealing
Authors: Kouvatsos D. N. , Ioannou-Sougleridis V. , Nassiopoulou A. G.
Published: January 2003

Metal–insulator–semiconductor structures with a layer of silicon nanocrystals embedded within the SiO2 layer at a tunneling distance from a p-type silicon substrate and fabricated using chemical vapor deposition, oxidation, and annealing, exhibited charge trapping, determined from the capacitance–voltage (C–V) characteristics, which abruptly increased at fields above 2.5 MV/cm. Electrons or holes are trapped when biasing the structure into inversion or accumulation, respectively, and retention of trapped charge is demonstrated. The I–V characteristics exhibit an N-shaped form, indicating screening effects due to charging; an initial current spike, attributed to transient charging of nanocrystals, occurs at the same voltage causing abrupt C–V shift increase, with Fowler–Nordheim current rising at higher voltages. These structures are promising for memory device applications.
Electroless metal discharge layers for electron beam lithography
Authors: Dobisz Elizabeth A. , Bass Robert , Brandow Susan L. , Chen Mu-San , Dressick Walter J.
Published: January 2003

We report a method for fabrication of continuous, conformal, ultrathin (i.e., 15–30 nm) Cu films using a room temperature, aqueous-based, electroless deposition technique on silica and polymer planarizer surfaces. The Cu films are sufficiently homogeneous, electrically conductive, and optically transparent for use as resist discharge layers during e-beam patterning of the substrate. The grounded Cu film, deployed here as a resist underlayer, eliminates the 0.1–0.4 μm subfield stitching errors normally observed in the absence of the Cu film during resist patterning on a glass or insulating substrate. The Cu is readily removed using a nitric acid wet etch following patterning.
Microscale to nanoscale ferroelectric domain and surface engineering of a near-stoichiometric LiNbO3 crystal
Authors: Terabe Kazuya , Nakamura Masaru , Takekawa Shunji , Kitamura Kenji , Higuchi Shinji , Gotoh Yoshihiko , Cho Yasuo
Published: January 2003

We have investigated microscale to nanoscale ferroelectric domain and surface engineering of a near-stoichiometric LiNbO3 crystal by using scanning force microscopy. The single crystals LiNbO3 fixed on metal substrates were polished to a 5 μm thickness. Artificial patterns of inverted-domain structures were fabricated in the samples, where polarization directions of the domains were switched by scanning the samples with a conductive cantilever while applying voltages. Furthermore, the negatively polarized surfaces in the patterns were preferentially etched in HF solution. As a result, cavity and mound-shaped surfaces were fabricated; these structures could be used to create functional templates and devices.
Transmission modulation in the passband of polystyrene photonic crystals
Authors: Guo Honglian , Chen Hongyi , Ni Peigen , Zhang Qi , Cheng Bingying , Zhang Daozhong
Published: January 2003

The periodic disturbance in transmittance of polystyrene photonic crystal is detected in our experiment. The peak-to-peak intervals of the periodic disturbance vary with the wavelength. It is attributed to the propagation of the whispering gallery mode in polystyrene spheres. The results show that the periodically arrayed particles may affect light transfer outside the gap band, which implies the possibility in applications of photonic crystal films.
Measurements of spin polarization of epitaxial SrRuO3 thin films
Authors: Nadgorny B. , Osofsky M. S. , Singh D. J. , Woods G. T. , Soulen R. J. , Lee M. K. , Bu S. D. , Eom C. B.
Published: January 2003

We have measured the transport spin polarization of epitaxial thin films of the conductive ferromagnetic oxide, SrRuO3, using point contact Andreev reflection spectroscopy. In spite of the fact that spin-up and spin-down electronic densities of states at the Fermi level for SrRuO3 calculated from band structure theory are practically the same, the experimental transport spin polarization for these films was found to be about 50%. This is a direct consequence of the Fermi velocity disparity between the majority and minority bands. The experimental results are compared with our theoretical estimates of the spin polarization in the ballistic and diffusive limits.
Coherent control of nuclear-spin system in a quantum-Hall device
Authors: Machida Tomoki , Yamazaki Tomoyuki , Ikushima Kenji , Komiyama Susumu
Published: January 2003

Coherent control of local nuclear spins in a solid-state device is demonstrated. By unequally populating spin-resolved quantum-Hall edge channels, nuclear spins in a limited region along the edge channels are strongly polarized via the hyperfine interaction. Pulsed rf magnetic fields, generated by a built-in micrometal strip, cause the nuclear-spin state to evolve coherently. The nuclear-spin state reached during the pulse duration is finally read out via the edge-channel conductance, which shows Rabi oscillation.
Mechanism for thermoelectric figure-of-merit enhancement in regimented quantum dot superlattices
Authors: Balandin Alexander A. , Lazarenkova Olga L.
Published: January 2003

We propose a mechanism for enhancement of the thermoelectric figure-of-merit in regimented quantum dot superlattices. A proof-of-concept calculation has been carried out for p-type regimented superlattice of Ge dots on Si. It is shown that when conditions for miniband formations are satisfied, carrier transport in such structures can be tuned in a favorable way leading to large carrier mobility, Seebeck coefficient, and, as a result, to the thermoelectric figure-of-merit enhancement. To maximize the improvement, one has to tune the parameters of quantum dot superlattice in such a way that electrical current is mostly through the well-separated minibands of relatively large width (at least several kBT, where kB is Boltzmann’s constant and T is temperature).
Fabrication of high-quality two-dimensional electron gases by overgrowth of focused-ion-beam-doped AlxGa1−xAs
Authors: Reuter D. , Riedesel C. , Schafmeister P. , Meier C. , Wieck A. D.
Published: January 2003

We have investigated two-dimensional electron gases (2DEGs) in inverted selectively doped GaAs/AlxGa1−xAs heterostructures fabricated by molecular-beam epitaxy (MBE) overgrowth of focused-ion-beam (FIB)-doped AlxGa1−xAs layers. In a first MBE step, the AlxGa1−xAs barrier was grown, before the sample was transferred to the FIB system. There, Si was implanted with 60 keV employing doses between 1×1012 and 1×1014 cm−2 and thereafter the sample was transferred back to the MBE system where the AlxGa1−xAs spacer as well as the GaAs top layer were grown. To protect the surface during the growth interruption, an amorphous As layer was used. Either an in situ annealing step before regrowth (30 s at 730 °C) or an ex situ thermal processing (30 s at 750 °C) after regrowth was used to remove the crystal damage due to the implantation. For the ex situ annealing step, we obtained mobilities up to 1.2×105 cm2/V s at 4.2 K after illumination whereas we observed mobilities up to 1.5×106 cm2/V s employing the in situ annealing step.
Hydrogen incorporation and diffusivity in plasma-exposed bulk ZnO
Authors: Ip K. , Overberg M. E. , Heo Y. W. , Norton D. P. , Pearton S. J. , Stutz C. E. , Luo B. , Ren F. , Look D. C. , Zavada J. M.
Published: January 2003

Hydrogen incorporation depths of >25 μm were obtained in bulk, single-crystal ZnO during exposure to H2 plasmas for 0.5 h at 300 °C, producing an estimated diffusivity of ∼8×10−10 cm2/V⋅s at this temperature. The activation energy for diffusion was 0.17±0.12 eV, indicating an interstitial mechanism. Subsequent annealing at 500–600 °C was sufficient to evolve all of the hydrogen out of the ZnO, at least to the sensitivity of secondary ion mass spectrometry (<5×1015 cm−3). The thermal stability of hydrogen retention is slightly greater when the hydrogen is incorporated by direct implantation relative to plasma exposure, due to trapping at residual damage in the former case.
Caspase- and Serine Protease-dependent Apoptosis by the Death Domain of FADD in Normal Epithelial Cells
Authors: Thorburn Jacqueline , Bender Laura M. , Morgan Michael J. , Thorburn Andrew
Published: January 2003

The adapter protein FADD consists of two protein interaction domains: a death domain and a death effector domain. The death domain binds to activated death receptors such as Fas, whereas the death effector domain binds to procaspase 8. An FADD mutant, which consists of only the death domain (FADD-DD), inhibits death receptor–induced apoptosis. FADD-DD can also activate a mechanistically distinct, cell type–specific apoptotic pathway that kills normal but not cancerous prostate epithelial cells. Here, we show that this apoptosis occurs through activation of caspases 9, 3, 6, and 7 and a serine protease. Simultaneous inhibition of caspases and serine proteases prevents FADD-DD–induced death. Inhibition of either pathway alone does not prevent cell death but does affect the morphology of the dying cells. Normal prostate epithelial cells require both the caspase and serine protease inhibitors to efficiently prevent apoptosis in response to TRAIL. In contrast, the serine protease inhibitor does not affect TRAIL-induced death in prostate tumor cells suggesting that the FADD-DD–dependent pathway can be activated by TRAIL. This apoptosis pathway is activated in a cell type–specific manner that is defective in cancer cells, suggesting that this pathway may be targeted during cancer development.
The Identification of Pats1, a Novel Gene Locus Required for Cytokinesis inDictyostelium discoideum
Authors: Abysalh Jonathan C. , Kuchnicki Lisa L. , Larochelle Denis A.
Published: January 2003

Here, we describe the identification and characterization of the cytokinesis-deficient mutant cell line 17HG5, which was generated in a restriction enzyme–mediated integration mutagenesis screen designed to isolate genes required for cytokinesis in Dictyostelium discoideum. Phenotypic characterization of the 17HG5 cell line revealed no apparent defects in the global functionality of the actomyosin cytoskeleton except for the observed cytokinesis defect when grown in suspension culture. Plasmid rescue was used to identify the disrupted gene locus (pats1; protein associated with the transduction of signal 1) that caused the cytokinesis defect. Disruption of the pats1 locus was recreated through homologous recombination in several independent cell lines, each recapitulating the cytokinesis-defective phenotype and thereby confirming that this gene locus is important for proper cytokinesis. Sequence data obtained by analysis of the genomic region flanking the inserted restriction enzyme–mediated integration plasmid revealed an 8892-bp genomic open reading frame encoding a 2964-amino-acid protein. The putative pats1 protein contains 3 regulatory domains (RI-phosphatase, RII-GTP–binding, R-III protein kinase), 13 leucine-rich repeats, and 8 WD-40 repeats. These regulatory domains coupled with the protein–protein interacting domains suggest that pats1 is involved in signal transduction during cytokinesis inDictyostelium.
Osteopontin Deficiency Produces Osteoclast Dysfunction Due to Reduced CD44 Surface Expression
Authors: Chellaiah M. A. , Kizer N. , Biswas R. , Alvarez U. , Strauss-Schoenberger J. , Rifas L. , Rittling S. R. , Denhardt D. T. , Hruska K. A.
Published: January 2003

Osteopontin (OPN) was expressed in murine wild-type osteoclasts, localized to the basolateral, clear zone, and ruffled border membranes, and deposited in the resorption pits during bone resorption. The lack of OPN secretion into the resorption bay of avian osteoclasts may be a component of their functional resorption deficiency in vitro. Osteoclasts deficient in OPN were hypomotile and exhibited decreased capacity for bone resorption in vitro. OPN stimulated CD44 expression on the osteoclast surface, and CD44 was shown to be required for osteoclast motility and bone resorption. Exogenous addition of OPN to OPN−/− osteoclasts increased the surface expression of CD44, and it rescued osteoclast motility due to activation of the αvβ3integrin. Exogenous OPN only partially restored bone resorption because addition of OPN failed to produce OPN secretion into resorption bays as seen in wild-type osteoclasts. As expected with these in vitro findings of osteoclast dysfunction, a bone phenotype, heretofore unappreciated, was characterized in OPN-deficient mice. Delayed bone resorption in metaphyseal trabeculae and diminished eroded perimeters despite an increase in osteoclast number were observed in histomorphometric measurements of tibiae isolated from OPN-deficient mice. The histomorphometric findings correlated with an increase in bone rigidity and moment of inertia revealed by load-to-failure testing of femurs. These findings demonstrate the role of OPN in osteoclast function and the requirement for OPN as an osteoclast autocrine factor during bone remodeling.
Time-lapse Imaging Reveals Dynamic Relocalization of PP1γ throughout the Mammalian Cell Cycle
Authors: Trinkle-Mulcahy Laura , Andrews Paul D. , Wickramasinghe Sasala , Sleeman Judith , Prescott Alan , Lam Yun Wah , Lyon Carol , Swedlow Jason R. , Lamond Angus I.
Published: January 2003

Protein phosphatase 1 (PP1) is a ubiquitous serine/threonine phosphatase that regulates many cellular processes, including cell division. When transiently expressed as fluorescent protein (FP) fusions, the three PP1 isoforms, α, β/δ, and γ1, are active phosphatases with distinct localization patterns. We report here the establishment and characterization of HeLa cell lines stably expressing either FP-PP1γ or FP alone. Time-lapse imaging reveals dynamic targeting of FP-PP1γ to specific sites throughout the cell cycle, contrasting with the diffuse pattern observed for FP alone. FP-PP1γ shows a nucleolar accumulation during interphase. On entry into mitosis, it localizes initially at kinetochores, where it exchanges rapidly with the diffuse cytoplasmic pool. A dramatic relocalization of PP1 to the chromosome-containing regions occurs at the transition from early to late anaphase, and by telophase FP-PP1γ also accumulates at the cleavage furrow and midbody. The changing spatio-temporal distribution of PP1γ revealed using the stable PP1 cell lines implicates it in multiple processes, including nucleolar function, the regulation of chromosome segregation and cytokinesis.
Cell Cycle-dependent Regulation of Structure of Endoplasmic Reticulum and Inositol 1,4,5-Trisphosphate-induced Ca2+Release in Mouse Oocytes and Embryos
Authors: FitzHarris Greg , Marangos Petros , Carroll John
Published: January 2003

The organization of endoplasmic reticulum (ER) was examined in mouse eggs undergoing fertilization and in embryos during the first cell cycle. The ER in meiosis II (MII)-arrested mouse eggs is characterized by accumulations (clusters) that are restricted to the cortex of the vegetal hemisphere of the egg. Monitoring ER structure with DiI18 after egg activation has demonstrated that ER clusters disappear at the completion of meiosis II. The ER clusters can be maintained by inhibiting the decrease in cdk1-cyclin B activity by using the proteasome inhibitor MG132, or by microinjecting excess cyclin B. A role for cdk1-cyclin B in ER organization is further suggested by the finding that the cdk inhibitor roscovitine causes the loss of ER clusters in MII eggs. Cortical clusters are specific to meiosis as they do not return in the first mitotic division; rather, the ER aggregates around the mitotic spindle. Inositol 1,4,5-trisphosphate-induced Ca2+release is also regulated in a cell cycle-dependent manner where it is increased in MII and in the first mitosis. The cell cycle dependent effects on ER structure and inositol 1,4,5-trisphosphate-induced Ca2+release have implications for understanding meiotic and mitotic control of ER structure and inheritance, and of the mechanisms regulating mitotic Ca2+signaling.
Global Transcriptional Responses of Fission Yeast to Environmental Stress
Authors: Chen Dongrong , Toone W. Mark , Mata Juan , Lyne Rachel , Burns Gavin , Kivinen Katja , Brazma Alvis , Jones Nic , Bähler Jürg
Published: January 2003

We explored transcriptional responses of the fission yeastSchizosaccharomyces pombe to various environmental stresses. DNA microarrays were used to characterize changes in expression profiles of all known and predicted genes in response to five stress conditions: oxidative stress caused by hydrogen peroxide, heavy metal stress caused by cadmium, heat shock caused by temperature increase to 39°C, osmotic stress caused by sorbitol, and DNA damage caused by the alkylating agent methylmethane sulfonate. We define a core environmental stress response (CESR) common to all, or most, stresses. There was a substantial overlap between CESR genes of fission yeast and the genes of budding yeast that are stereotypically regulated during stress. CESR genes were controlled primarily by the stress-activated mitogen-activated protein kinase Sty1p and the transcription factor Atf1p. S. pombe also activated gene expression programs more specialized for a given stress or a subset of stresses. In general, these “stress-specific” responses were less dependent on the Sty1p mitogen-activated protein kinase pathway and may involve specific regulatory factors. Promoter motifs associated with some of the groups of coregulated genes were identified. We compare and contrast global regulation of stress genes in fission and budding yeasts and discuss evolutionary implications.
Cross-Species Sequence Comparisons: A Review of Methods and Available Resources
Authors: Frazer Kelly A. , Elnitski Laura , Church Deanna M. , Dubchak Inna , Hardison Ross C.
Published: January 2003

With the availability of whole-genome sequences for an increasing number of species, we are now faced with the challenge of decoding the information contained within these DNA sequences. Comparative analysis of DNA sequences from multiple species at varying evolutionary distances is a powerful approach for identifying coding and functional noncoding sequences, as well as sequences that are unique for a given organism. In this review, we outline the strategy for choosing DNA sequences from different species for comparative analyses and describe the methods used and the resources publicly available for these studies.
Reevaluating Human Gene Annotation: A Second-Generation Analysis of Chromosome 22
Authors: Collins John E. , Goward Melanie E. , Cole Charlotte G. , Smink Luc J. , Huckle Elizabeth J. , Knowles Sarah , Bye Jacqueline M. , Beare David M. , Dunham Ian
Published: January 2003

We report a second-generation gene annotation of human chromosome 22. Using expressed sequence databases, comparative sequence analysis, and experimental verification, we have extended genes, fused previously fragmented structures, and identified new genes. The total length in exons of annotation was increased by 74% over our previously published annotation and includes 546 protein-coding genes and 234 pseudogenes. Thirty-two potential protein-coding annotations are partial copies of other genes, and may represent duplications on an evolutionary path to change or loss of function. We also identified 31 non-protein-coding transcripts, including 16 possible antisense RNAs. By extrapolation, we estimate the human genome contains 29,000–36,000 protein-coding genes, 21,300 pseudogenes, and 1500 antisense RNAs. We suggest that our revised annotation criteria provide a paradigm for future annotation of the human genome.

[Supplemental material is available online at www.genome.org. The sequence data from this study have been submitted to GenBank under accession nos. AL009266, AL021682-3,AL021708, AL022729, AL035081-2, AL035364, AL035366, AL035545, AL049654,AL050253-8, AL050345-6, AL079310, AL096779-81, AL096879-81, AL096883,AL096886, AL138578, AL157851, AL159142-3, AL160111-2, AL160131-2,AL160311, AL355092, AL355192, AL355841, AL359401, AL359403, AL365511-5,AL442116, AL449243, AL449244, AL450314, AL589866-7, AL590120,AL590887-8, BU583989–BU585359. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: J. Seilhamer, L. Stuve, H. Roest-Crollius, A. Levine, G. Slater, and J. Kent.]
The Phusion Assembler
Authors: Mullikin James C. , Ning Zemin
Published: January 2003

The Phusion assembler has assembled the mouse genome from the whole-genome shotgun (WGS) dataset collected by the Mouse Genome Sequencing Consortium, at ∼7.5× sequence coverage, producing a high-quality draft assembly 2.6 gigabases in size, of which 90% of these bases are in 479 scaffolds. For the mouse genome, which is a large and repeat-rich genome, the input dataset was designed to include a high proportion of paired end sequences of various size selected inserts, from 2–200 kbp lengths, into various host vector templates. Phusion uses sequence data, called reads, and information about reads that share common templates, called read pairs, to drive the assembly of this large genome to highly accurate results. The preassembly stage, which clusters the reads into sensible groups, is a key element of the entire assembler, because it permits a simple approach to parallelization of the assembly stage, as each cluster can be treated independent of the others. In addition to the application of Phusion to the mouse genome, we will also present results from the WGS assembly ofCaenorhabditis briggsae sequenced to about 11× coverage. TheC. briggsae assembly was accessioned through EMBL,http://www.ebi.ac.uk/services/index.html, using the series CAAC01000001–CAAC01000578, however, the Phusion mouse assembly described here was not accessioned. The mouse data was generated by the Mouse Genome Sequencing Consortium. The C. briggsae sequence was generated at The Wellcome Trust Sanger Institute and the Genome Sequencing Center, Washington University School of Medicine.
Genome Rearrangements in Mammalian Evolution: Lessons From Human and Mouse Genomes
Authors: Pevzner Pavel , Tesler Glenn
Published: January 2003

Although analysis of genome rearrangements was pioneered by Dobzhansky and Sturtevant 65 years ago, we still know very little about the rearrangement events that produced the existing varieties of genomic architectures. The genomic sequences of human and mouse provide evidence for a larger number of rearrangements than previously thought and shed some light on previously unknown features of mammalian evolution. In particular, they reveal that a large number of microrearrangements is required to explain the differences in draft human and mouse sequences. Here we describe a new algorithm for constructing synteny blocks, study arrangements of synteny blocks in human and mouse, derive a most parsimonious human–mouse rearrangement scenario, and provide evidence that intrachromosomal rearrangements are more frequent than interchromosomal rearrangements. Our analysis is based on the human–mouse breakpoint graph, which reveals related breakpoints and allows one to find a most parsimonious scenario. Because these graphs provide important insights into rearrangement scenarios, we introduce a new visualization tool that allows one to view breakpoint graphs superimposed with genomic dot-plots.

[Supplemental material is available online atwww.genome.org.]
Strategies and Tools for Whole-Genome Alignments
Authors: Couronne Olivier , Poliakov Alexander , Bray Nicolas , Ishkhanov Tigran , Ryaboy Dmitriy , Rubin Edward , Pachter Lior , Dubchak Inna
Published: January 2003

The availability of the assembled mouse genome makes possible, for the first time, an alignment and comparison of two large vertebrate genomes. We investigated different strategies of alignment for the subsequent analysis of conservation of genomes that are effective for assemblies of different quality. These strategies were applied to the comparison of the working draft of the human genome with the Mouse Genome Sequencing Consortium assembly, as well as other intermediate mouse assemblies. Our methods are fast and the resulting alignments exhibit a high degree of sensitivity, covering more than 90% of known coding exons in the human genome. We obtained such coverage while preserving specificity. With a view towards the end user, we developed a suite of tools and Web sites for automatically aligning and subsequently browsing and working with whole-genome comparisons. We describe the use of these tools to identify conserved non-coding regions between the human and mouse genomes, some of which have not been identified by other methods.
Multiple Cross and Inbred Strain Haplotype Mapping of Complex-Trait Candidate Genes: Figure 1.
Authors: Park Yeong-Gwon , Clifford Robert , Buetow Kenneth H. , Hunter Kent W.
Published: January 2003

Identifying complex-trait candidate genes after initial low-resolution mapping has proven to be a difficult and labor-intensive undertaking, usually requiring years to develop and analyze congenic strains. As a result, to date, few complex-trait genes have been discovered. Recently it was suggested that SNP haplotype analysis in inbred strains might be useful for mapping of complex traits. In this study, we have combined medium-resolution haplotype mapping with multiple experimental cross-mapping experiments to reduce the number of potential candidate genes in a complex-trait candidate interval. Coincident mapping of a modifier gene in multiple experimental crosses using different inbred strains is consistent with the common inheritance of a modifier allele. A haplotype map was developed in four inbred strains of mice used in our complex-trait mapping crosses across the proximal 10 cM of proximal Chromosome 19 to identify haplotype blocks that segregate appropriately. Only ∼23 out of >400 genes met this criteria. This strategy coupled with tissue and expression arrays, as well as our recently described common pathway analysis to reduce the number of high-priority candidates, may provide a rapid, efficient method to identify and prioritize complex-trait candidate genes without requiring construction of congenic mouse strains.
AVID: A Global Alignment Program
Authors: Bray Nick , Dubchak Inna , Pachter Lior
Published: January 2003

In this paper we describe a new global alignment method called AVID. The method is designed to be fast, memory efficient, and practical for sequence alignments of large genomic regions up to megabases long. We present numerous applications of the method, ranging from the comparison of assemblies to alignment of large syntenic genomic regions and whole genome human/mouse alignments. We have also performed a quantitative comparison of AVID with other popular alignment tools. To this end, we have established a format for the representation of alignments and methods for their comparison. These formats and methods should be useful for future studies. The tools we have developed for the alignment comparisons, as well as the AVID program, are publicly available. See Web Site References section for AVID Web address and Web addresses for other programs discussed in this paper.
Pericentromeric Duplications in the Laboratory Mouse
Authors: Thomas James W. , Schueler Mary G. , Summers Tyrone J. , Blakesley Robert W. , McDowell Jennifer C. , Thomas Pamela J. , Idol Jacquelyn R. , Maduro Valerie V.B. , Lee-Lin Shih-Queen , Touchman Jeffrey W. , Bouffard Gerard G. , Beckstrom-Sternberg Stephen M. , Program NISC Comparative Sequencing , Green Eric D.
Published: January 2003

Duplications have long been postulated to be an important mechanism by which genomes evolve. Interspecies genomic comparisons are one method by which the origin and molecular mechanism of duplications can be inferred. By comparative mapping in human, mouse, and rat, we previously found evidence for a recent chromosome-fission event that occurred in the mouse lineage. Cytogenetic mapping revealed that the genomic segments flanking the fission site appeared to be duplicated, with copies residing near the centromere of multiple mouse chromosomes. Here we report the mapping and sequencing of the regions of mouse chromosomes 5 and 6 involved in this chromosome-fission event as well as the results of comparative sequence analysis with the orthologous human and rat genomic regions. Our data indicate that the duplications associated with mouse chromosomes 5 and 6 are recent and that the resulting duplicated segments share significant sequence similarity with a series of regions near the centromeres of the mouse chromosomes previously identified by cytogenetic mapping. We also identified pericentromeric duplicated segments shared between mouse chromosomes 5 and 1. Finally, novel mouse satellite sequences as well as putative chimeric transcripts were found to be associated with the duplicated segments. Together, these findings demonstrate that pericentromeric duplications are not restricted to primates and may be a common mechanism for genome evolution in mammals.

[Supplemental material is available online at www.genome.org.]
Human–Mouse Alignments with BLASTZ
Authors: Schwartz Scott , Kent W. James , Smit Arian , Zhang Zheng , Baertsch Robert , Hardison Ross C. , Haussler David , Miller Webb
Published: January 2003

The Mouse Genome Analysis Consortium aligned the human and mouse genome sequences for a variety of purposes, using alignment programs that suited the various needs. For investigating issues regarding genome evolution, a particularly sensitive method was needed to permit alignment of a large proportion of the neutrally evolving regions. We selected a program called BLASTZ, an independent implementation of the Gapped BLAST algorithm specifically designed for aligning two long genomic sequences. BLASTZ was subsequently modified, both to attain efficiency adequate for aligning entire mammalian genomes and to increase its sensitivity. This work describes BLASTZ, its modifications, the hardware environment on which we run it, and several empirical studies to validate its results.
Distinguishing Regulatory DNA From Neutral Sites
Authors: Elnitski Laura , Hardison Ross C. , Li Jia , Yang Shan , Kolbe Diana , Eswara Pallavi , O'Connor Michael J. , Schwartz Scott , Miller Webb , Chiaromonte Francesca
Published: January 2003

We explore several computational approaches to analyzing interspecies genomic sequence alignments, aiming to distinguish regulatory regions from neutrally evolving DNA. Human–mouse genomic alignments were collected for three sets of human regions: (1) experimentally defined gene regulatory regions, (2) well-characterized exons (coding sequences, as a positive control), and (3) interspersed repeats thought to have inserted before the human–mouse split (a good model for neutrally evolving DNA). Models that potentially could distinguish functional noncoding sequences from neutral DNA were evaluated on these three data sets, as well as bulk genome alignments. Our analyses show that discrimination based on frequencies of individual nucleotide pairs or gaps (i.e., of possible alignment columns) is only partially successful. In contrast, scoring procedures that include the alignment context, based on frequencies of short runs of alignment columns, dramatically improve separation between regulatory and neutral features. Such scoring functions should aid in the identification of putative regulatory regions throughout the human genome.
Whole-Genome Sequence Assembly for Mammalian Genomes: Arachne 2
Authors: Jaffe David B. , Butler Jonathan , Gnerre Sante , Mauceli Evan , Lindblad-Toh Kerstin , Mesirov Jill P. , Zody Michael C. , Lander Eric S.
Published: January 2003

We previously described the whole-genome assembly program Arachne, presenting assemblies of simulated data for small to mid-sized genomes. Here we describe algorithmic adaptations to the program, allowing for assembly of mammalian-size genomes, and also improving the assembly of smaller genomes. Three principal changes were simultaneously made and applied to the assembly of the mouse genome, during a six-month period of development: (1) Supercontigs (scaffolds) were iteratively broken and rejoined using several criteria, yielding a 64-fold increase in length (N50), and apparent elimination of all global misjoins; (2) gaps between contigs in supercontigs were filled (partially or completely) by insertion of reads, as suggested by pairing within the supercontig, increasing the N50 contig length by 50%; (3) memory usage was reduced fourfold. The outcome of this mouse assembly and its analysis are described in (Mouse Genome Sequencing Consortium 2002).
Leveraging the Mouse Genome for Gene Prediction in Human: From Whole-Genome Shotgun Reads to a Global Synteny Map
Authors: Flicek Paul , Keibler Evan , Hu Ping , Korf Ian , Brent Michael R.
Published: January 2003

The availability of draft sequences for both the mouse and human genomes makes it possible, for the first time, to annotate whole mammalian genomes using comparative methods. TWINSCAN is a gene-prediction system that combines the methods of single-genome predictors like GENSCAN with information derived from genome comparison, thereby improving accuracy. Because TWINSCAN uses genomic sequence only, it is less biased toward highly and/or ubiquitously expressed genes than GENEWISE, GENOMESCAN, and other methods based on evidence derived from transcripts. We show that TWINSCAN improves gene prediction in human using intermediate products from various stages of the sequencing and analysis of the mouse genome, from low-redundancy, whole-genome shotgun reads to the draft assembly and the synteny map. TWINSCAN improves on the prior state of the art even when alignments from only 1X coverage of the mouse genome are available. Gene prediction accuracy improves steadily from 1X through 3X, more slowly from 3X to 4X, and relatively little thereafter. The assembly and the synteny map greatly speed the computations, however. Our human annotation using the mouse assembly is conservative, predicting only 25,622 genes, and appears to be one of the best de novo annotations of the human genome to date.
Covariation in Frequencies of Substitution, Deletion, Transposition, and Recombination During Eutherian Evolution
Authors: Hardison Ross C. , Roskin Krishna M. , Yang Shan , Diekhans Mark , Kent W. James , Weber Ryan , Elnitski Laura , Li Jia , O'Connor Michael , Kolbe Diana , Schwartz Scott , Furey Terrence S. , Whelan Simon , Goldman Nick , Smit Arian , Miller Webb , Chiaromonte Francesca , Haussler David
Published: January 2003

Six measures of evolutionary change in the human genome were studied, three derived from the aligned human and mouse genomes in conjunction with the Mouse Genome Sequencing Consortium, consisting of (1) nucleotide substitution per fourfold degenerate site in coding regions, (2) nucleotide substitution per site in relics of transposable elements active only before the human–mouse speciation, and (3) the nonaligning fraction of human DNA that is nonrepetitive or in ancestral repeats; and three derived from human genome data alone, consisting of (4) SNP density, (5) frequency of insertion of transposable elements, and (6) rate of recombination. Features 1 and 2 are measures of nucleotide substitutions at two classes of “neutral” sites, whereas 4 is a measure of recent mutations. Feature 3 is a measure dominated by deletions in mouse, whereas 5 represents insertions in human. It was found that all six vary significantly in megabase-sized regions genome-wide, and many vary together. This indicates that some regions of a genome change slowly by all processes that alter DNA, and others change faster. Regional variation in all processes is correlated with, but not completely accounted for, by GC content in human and the difference between GC content in human and mouse. [Supplemental material is available online atwww.genome.organdhttp://www.soe.ucsc.edu/research/compbio/covariation/.]