bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of alloy buffer and capping layers on InAs/GaAs quantum dot formation
Authors: Dasika V. D. , Song J. D. , Choi W. J. , Cho N. K. , Lee J. I. , Goldman R. S.
Published: October 2009

We have investigated the influence of alloy buffer and capping layers on the shape, size, and density of self-assembled InAs/GaAs quantum dots. Cross-sectional scanning tunneling microscopy (XSTM) images reveal ellipse-shaped dots with highest (lowest) diameter, height, and density, for dots with (without) surrounding alloy layers. Furthermore, the wetting layer is thicker in the presence of the alloy layers. We propose a strain-based mechanism for dot formation and collapse in the absence and presence of alloy buffer and capping layers. This mechanism is likely to be applicable to a wide range of lattice-mismatched thin-film systems.
Glass transition and crystallization dynamics of thin CCl2F2 films deposited on Ni(111), graphite, and water-ice films
Authors: Souda Ryutaro
Published: October 2009

The glass-liquid transition and crystallization of thin CCl2F2 films, as well as the influence of substrates on the phase transition of a monolayer, have been investigated using temperature-programmed time-of-flight secondary ion mass spectrometry. The multilayer films of CCl2F2 dewet a Ni(111) substrate abruptly at 57 K, which is explainable as immediate crystallization of supercooled liquid. The morphology of the crystalline CCl2F2 film changes at 85 K; the molecules permeate through porous D2O films at temperatures higher than 70 K. These behaviors can be explained as the evolution of a second liquid or premelting of crystallites. The monolayer of CCl2F2 formed on graphite undergoes a phase transition similar to that of the multilayer films, whereas the phase transition is quenched for the monolayer formed on the Ni(111) substrate. The phase transition of the CCl2F2 monolayer formed on the D2O film is influenced by crystallinity, thickness, and morphology of the latter.
Wavelength-sized cavities in high aspect InP/InGaAsP/InP photonic crystals
Authors: Kicken H. H. J. E. , Barbu I. , van der Heijden R. W. , Karouta F. , Nötzel R. , van der Drift E. , Salemink H. W. M.
Published: October 2009

The photonic properties of two classes of wavelength-sized cavities are reported for deeply etched InP/InGaAsP/InP planar photonic crystals. The high aspect, deeply etched structures are studied as potential building blocks for nonmembrane type photonic devices in standard InP photonic integrated circuits. The first class consists of cavities of one unit cell in one direction and varying size in the other planar direction. The studied class includes a Fabry–Perot type cavity with one row of missing holes, a simple single missing hole defect cavity, and a cavity consisting of two holes which have been slightly shifted and reduced in hole radius. The best observed quality factor of 65 in this class is obtained for a single hole defect cavity. The second class is comprised of cavities which are derived from a three missing row defect in one direction and varying size in the other direction. This includes a Fabry–Perot type cavity with three rows of missing holes, a point defect cavity consisting of seven unetched holes and a six hole ring cavity. The best observed quality factor of 300 is obtained for the ring cavity in this second class of structures, which is adequate for applications.
Effects of annealing and substrate orientation on epitaxial growth of GaAs on Si
Authors: Xu H. Y. , Guo Y. N. , Wang Y. , Zou J. , Kang J. H. , Gao Q. , Tan H. H. , Jagadish C.
Published: October 2009

GaAs thin films grown on Si (100) and (111) substrates by metal-organic chemical vapor deposition were investigated by electron microscopy. It was found that the growth rate of the GaAs epitaxial layers on Si (100) was faster than that on Si (111) due to a lower Si (111) surface energy. The morphologies and internal crystal structure quality of GaAs films grown on Si (111) were better than those grown on Si (100). It was also found that postannealing at high temperature can improve the morphology of the epitaxial layer surface and reduce lattice defects in the thin films.
1H NMR metabolomics of earthworm responses to sub-lethal PAH exposure
Authors: Brown Sarah A. E. , Simpson Andre J. , Simpson Myrna J.
Published: October 2009

Environmental context. Polycyclic aromatic hydrocarbons (PAHs) are common contaminants, but there has been limited research investigating the responses of earthworm exposure to sub-lethal PAH concentrations. In this study, 1H nuclear magnetic resonance (NMR) metabolomics was used to characterise the metabolic responses of Eisenia fetida earthworm exposure in contact tests to 10, 50 and 100 μg cm–2 naphthalene, phenanthrene and pyrene. The findings of this study highlight the potential of metabolomics as a tool for monitoring earthworm responses to sub-lethal concentrations of problematic environmental contaminants.
Abstract. Metabolic responses of earthworm exposure to the polycyclic aromatic hydrocarbons (PAHs) naphthalene, phenanthrene and pyrene in contact tests were measured using 1H nuclear magnetic resonance (NMR). Novel metabolites were not detected but principal component analysis (PCA) showed that earthworms exposed to 10, 50 and 100 μg cm–2 naphthalene, phenanthrene and pyrene differed from unexposed (control) earthworms. Partial least-squares-discriminant analysis (PLS-DA) showed that earthworms had statistically significant responses to PAH exposure, except for 10 μg cm–2 naphthalene and 50 μg cm–2 pyrene. Leucine, valine, alanine, lysine and maltose were identified as potential response indicators of PAH exposure, but whether the concentration of these metabolites increased or decreased was PAH- and concentration-dependent. These initial findings reveal the potential of metabolomics for monitoring earthworm responses to sub-lethal PAH exposure and highlight the role of metabolomics as a future tool in ecotoxicology.
Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition
Authors: Siegrist M. Sloan , Unnikrishnan Meera , McConnell Matthew J. , Borowsky Mark , Cheng Tan-Yun , Siddiqi Noman , Fortune Sarah M. , Moody D. Branch , Rubin Eric J.
Published: October 2009

The Esx secretion pathway is conserved across Gram-positive bacteria. Esx-1, the best-characterized system, is required for virulence ofMycobacterium tuberculosis, although its precise function during infection remains unclear. Esx-3, a paralogous system present in all mycobacterial species, is required for growth in vitro. Here, we demonstrate that mycobacteria lacking Esx-3 are defective in acquiring iron. To compete for the limited iron available in the host and the environment, these organisms use mycobactin, high-affinity iron-binding molecules. In the absence of Esx-3, mycobacteria synthesize mycobactin but are unable to use the bound iron and are impaired severely for growth during macrophage infection. Mycobacteria thus require a specialized secretion system for acquiring iron from siderophores.
Pharmacological modulation of subliminal learning in Parkinson's and Tourette's syndromes
Authors: Palminteri Stefano , Lebreton Maël , Worbe Yulia , Grabli David , Hartmann Andreas , Pessiglione Mathias
Published: October 2009

Theories of instrumental learning aim to elucidate the mechanisms that integrate success and failure to improve future decisions. One computational solution consists of updating the value of choices in proportion to reward prediction errors, which are potentially encoded in dopamine signals. Accordingly, drugs that modulate dopamine transmission were shown to impact instrumental learning performance. However, whether these drugs act on conscious or subconscious learning processes remains unclear. To address this issue, we examined the effects of dopamine-related medications in a subliminal instrumental learning paradigm. To assess generality of dopamine implication, we tested both dopamine enhancers in Parkinson's disease (PD) and dopamine blockers in Tourette's syndrome (TS). During the task, patients had to learn from monetary outcomes the expected value of a risky choice. The different outcomes (rewards and punishments) were announced by visual cues, which were masked such that patients could not consciously perceive them. Boosting dopamine transmission in PD patients improved reward learning but worsened punishment avoidance. Conversely, blocking dopamine transmission in TS patients favored punishment avoidance but impaired reward seeking. These results thus extend previous findings in PD to subliminal situations and to another pathological condition, TS. More generally, they suggest that pharmacological manipulation of dopamine transmission can subconsciously drive us to either get more rewards or avoid more punishments.
Ligand migration through the internal hydrophobic cavities in human neuroglobin
Authors: Abbruzzetti Stefania , Faggiano Serena , Bruno Stefano , Spyrakis Francesca , Mozzarelli Andrea , Dewilde Sylvia , Moens Luc , Viappiani Cristiano
Published: October 2009

Neuroglobin (Ngb), a member of the globin superfamily, was found in the brain of vertebrates and is suggested to play a neuroprotective function under hypoxic conditions by scavenging nitrogen monoxide (NO) through a dioxygenase activity. In order for such a reaction to efficiently take place and to minimize the release of reactive intermediates in the cytosol, the cosubstrates O
2
and NO and other unstable reaction intermediates should bind sequentially to docking sites in the protein matrix. We have characterized the accessibility of these sites by analyzing the geminate CO rebinding kinetics to the heme moiety observed upon nanosecond flash photolysis of the Ngb-CO complex encapsulated in silica gels. The geminate rebinding phase showed a remarkable complexity, revealing the presence of a system of secondary docking sites where ligands are stored for hundreds of microseconds. Most kinetics steps display little temperature dependence, demonstrating that ligands can easily migrate through the cavities, except for the slowest reaction intermediate, possibly reflecting a structural conformational change reshaping the system of cavities. This conformational change is unrelated with distal His E7 binding to the heme, as it persists for the HE7L mutant. Overall, data are consistent with the presence of a discrete system of docking sites, possibly acting as reservoirs for the putative cosubstrates and for other reactive species involved in the physiologically relevant reaction.
Elevated CO2suppresses specific Drosophila innate immune responses and resistance to bacterial infection
Authors: Helenius Iiro Taneli , Krupinski Thomas , Turnbull Douglas W. , Gruenbaum Yosef , Silverman Neal , Johnson Eric A. , Sporn Peter H. S. , Sznajder Jacob I. , Beitel Greg J.
Published: October 2009

Elevated CO2levels (hypercapnia) frequently occur in patients with obstructive pulmonary diseases and are associated with increased mortality. However, the effects of hypercapnia on non-neuronal tissues and the mechanisms that mediate these effects are largely unknown. Here, we developDrosophilaas a genetically tractable model for defining non-neuronal CO2responses and response pathways. We show that hypercapnia significantly impairs embryonic morphogenesis, egg laying, and egg hatching even in mutants lacking the Gr63a neuronal CO2sensor. Consistent with previous reports that hypercapnic acidosis can suppress mammalian NF-κB-regulated innate immune genes, we find that in adult flies and the phagocytic immune-responsive S2* cell line, hypercapnia suppresses induction of specific antimicrobial peptides that are regulated by Relish, a conserved Rel/NF-κB family member. Correspondingly, modest hypercapnia (7–13%) increases mortality of flies inoculated withE. faecalis,A. tumefaciens, orS. aureus. DuringE. faecalisandA. tumefaciensinfection, increased bacterial loads were observed, indicating that hypercapnia can decrease host resistance. Hypercapnic immune suppression is not mediated by acidosis, the olfactory CO2receptor Gr63a, or by nitric oxide signaling. Further, hypercapnia does not induce responses characteristic of hypoxia, oxidative stress, or heat shock. Finally, proteolysis of the Relish IκB-like domain is unaffected by hypercapnia, indicating that immunosuppression acts downstream of, or in parallel to, Relish proteolytic activation. Our results suggest that hypercapnic immune suppression is mediated by a conserved response pathway, and illustrate a mechanism by which hypercapnia could contribute to worse outcomes of patients with advanced lung disease, who frequently suffer from both hypercapnia and respiratory infections.
Insights into the reactivation of cobalamin-dependent methionine synthase
Authors: Koutmos Markos , Datta Supratim , Pattridge Katherine A. , Smith Janet L. , Matthews Rowena G.
Published: October 2009

Cobalamin-dependent methionine synthase (MetH) is a modular protein that catalyzes the transfer of a methyl group from methyltetrahydrofolate to homocysteine to produce methionine and tetrahydrofolate. The cobalamin cofactor, which serves as both acceptor and donor of the methyl group, is oxidized once every ≈2,000 catalytic cycles and must be reactivated by the uptake of an electron from reduced flavodoxin and a methyl group from
S
-adenosyl-L-methionine (AdoMet). Previous structures of a C-terminal fragment of MetH (MetH
CT
) revealed a reactivation conformation that juxtaposes the cobalamin- and AdoMet-binding domains. Here we describe 2 structures of a disulfide stabilized MetH
CT
(

s-s

MetH
CT
) that offer further insight into the reactivation of MetH. The structure of

s-s

MetH
CT
with cob(II)alamin and
S
-adenosyl-L-homocysteine represents the enzyme in the reactivation step preceding electron transfer from flavodoxin. The structure supports earlier suggestions that the enzyme acts to lower the reduction potential of the Co(II)/Co(I) couple by elongating the bond between the cobalt and its upper axial water ligand, effectively making the cobalt 4-coordinate, and illuminates the role of Tyr-1139 in the stabilization of this 4-coordinate state. The structure of

s-s

MetH
CT
with aquocobalamin may represent a transient state at the end of reactivation as the newly remethylated 5-coordinate methylcobalamin returns to the 6-coordinate state, triggering the rearrangement to a catalytic conformation.
Ultrafast photochemistry of methyl hydroperoxide on ice particles
Authors: Kamboures M. A. , Nizkorodov S. A. , Gerber R. B.
Published: October 2009

Simulations show that photodissociation of methyl hydroperoxide, CH
3
OOH, on water clusters produces a surprisingly wide range of products on a subpicosecond time scale, pointing to the possibility of complex photodegradation pathways for organic peroxides on aerosols and water droplets. Dynamics are computed at several excitation energies at 50 K using a semiempirical PM3 potential surface. CH
3
OOH is found to prefer the exterior of the cluster, with the CH
3
O group sticking out and the OH group immersed within the cluster. At atmospherically relevant photodissociation wavelengths the OH and CH
3
O photofragments remain at the surface of the cluster or embedded within it. However, none of the 25 completed trajectories carried out at the atmospherically relevant photodissociation energies led to recombination of OH and CH
3
O to form CH
3
OOH. Within the limited statistics of the available trajectories the predicted yield for the recombination is zero. Instead, various reactions involving the initial fragments and water promptly form a wide range of stable molecular products such as CH
2
O, H
2
O, H
2
, CO, CH
3
OH, and H
2
O
2
.
X-ray structure of Pur-α reveals a Whirly-like fold and an unusual nucleic-acid binding surface
Authors: Graebsch Almut , Roche Stéphane , Niessing Dierk
Published: October 2009

The PUR protein family is a distinct and highly conserved class that is characterized by its sequence-specific RNA- and DNA-binding. Its best-studied family member, Pur-α, acts as a transcriptional regulator, as host factor for viral replication, and as cofactor for mRNP localization in dendrites. Pur-α-deficient mice show severe neurologic defects and die after birth. Nucleic-acid binding by Pur-α is mediated by its central core region, for which no structural information is available. We determined the x-ray structure of residues 40 to 185 from
Drosophila melanogaster
Pur-α, which constitutes a major part of the core region. We found that this region contains two almost identical structural motifs, termed “PUR repeats,” which interact with each other to form a PUR domain. DNA- and RNA-binding studies confirmed that PUR domains are indeed functional nucleic-acid binding domains. Database analysis show that PUR domains share a fold with the Whirly class of nucleic-acid binding proteins. Structural analysis combined with mutational studies suggest that a PUR domain binds nucleic acids through two independent surface regions involving concave β-sheets. Structure-based sequence alignment revealed that the core region harbors a third PUR repeat at its C terminus. Subsequent characterization by small-angle x-ray scattering (SAXS) and size-exclusion chromatography indicated that PUR repeat III mediates dimerization of Pur-α. Surface envelopes calculated from SAXS data show that the Pur-α dimer consisting of repeats I to III is arranged in a Z-like shape. This unexpected domain organization of the entire core domain of Pur-α has direct implications for ssDNA/ssRNA and dsDNA binding.
Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases
Authors:   International MHC and Autoimmunity Genetics Network (IMAGEN)*, Rioux John D. , Goyette Philippe , Vyse Timothy J. , Hammarström Lennart , Fernando Michelle M. A. , Green Todd , De Jager Philip L. , Foisy Sylvain , Wang Joanne , de Bakker Paul I. W. , Leslie Stephen , McVean Gilean , Padyukov Leonid , Alfredsson Lars , Annese Vito , Hafler David A. , Pan-Hammarström Qiang , Matell Ritva , Sawcer Stephen J. , Compston Alastair D. , Cree Bruce A. C. , Mirel Daniel B. , Daly Mark J. , Behrens Tim W. , Klareskog Lars , Gregersen Peter K. , Oksenberg Jorge R. , Hauser Stephen L.
Published: October 2009

The human MHC represents the strongest susceptibility locus for autoimmune diseases. However, the identification of the true predisposing gene(s) has been handicapped by the strong linkage disequilibrium across the region. Furthermore, most studies to date have been limited to the examination of a subset of the HLA and non-HLA genes with a marker density and sample size insufficient for mapping all independent association signals. We genotyped a panel of 1,472 SNPs to capture the common genomic variation across the 3.44 megabase (Mb) classic MHC region in 10,576 DNA samples derived from patients with systemic lupus erythematosus, Crohn's disease, ulcerative colitis, rheumatoid arthritis, myasthenia gravis, selective IgA deficiency, multiple sclerosis, and appropriate control samples. We identified the primary association signals for each disease and performed conditional regression to identify independent secondary signals. The data demonstrate that MHC associations with autoimmune diseases result from complex, multilocus effects that span the entire region.
Activation of nuclear receptor CAR ameliorates diabetes and fatty liver disease
Authors: Dong Bingning , Saha Pradip K. , Huang Wendong , Chen Wenling , Abu-Elheiga Lutfi A. , Wakil Salih J. , Stevens Robert D. , Ilkayeva Olga , Newgard Christopher B. , Chan Lawrence , Moore David D.
Published: October 2009

Constitutive androstane receptor CAR (NR1I3) has been identified as a central mediator of coordinate responses to xenobiotic and endobiotic stress. Here we use leptin-deficient mice (ob/ob) and ob/ob, CAR
−/−
double mutant mice to identify a metabolic role of CAR in type 2 diabetes. Activation of CAR significantly reduces serum glucose levels and improves glucose tolerance and insulin sensitivity. Gene expression analyses and hyperinsulinemic euglycemic clamp results suggest that CAR activation ameliorates hyperglycemia by suppressing glucose production and stimulating glucose uptake and usage in the liver. In addition, CAR activation dramatically improves fatty liver by both inhibition of hepatic lipogenesis and induction of β-oxidation. We conclude that CAR activation improves type 2 diabetes, and that these actions of CAR suggest therapeutic approaches to the disease.
Neural representation of time in cortico-basal ganglia circuits
Authors: Jin Dezhe Z. , Fujii Naotaka , Graybiel Ann M.
Published: October 2009

Encoding time is universally required for learning and structuring motor and cognitive actions, but how the brain keeps track of time is still not understood. We searched for time representations in cortico-basal ganglia circuits by recording from thousands of neurons in the prefrontal cortex and striatum of macaque monkeys performing a routine visuomotor task. We found that a subset of neurons exhibited time-stamp encoding strikingly similar to that required by models of reinforcement-based learning: They responded with spike activity peaks that were distributed at different time delays after single task events. Moreover, the temporal evolution of the population activity allowed robust decoding of task time by perceptron models. We suggest that time information can emerge as a byproduct of event coding in cortico-basal ganglia circuits and can serve as a critical infrastructure for behavioral learning and performance.
In ovo
application of antagomiRs indicates a role for miR-196 in patterning the chick axial skeleton through Hox gene regulation
Authors: McGlinn Edwina , Yekta Soraya , Mansfield Jennifer H. , Soutschek Jürgen , Bartel David P. , Tabin Clifford J.
Published: October 2009

Patterning of the vertebrate axial skeleton requires precise spatial and temporal control of Hox gene expression during embryonic development. MicroRNAs (miRNAs) are recently described modulators of gene activity, and members of the miR-196 and miR-10 families have been shown to target several Hox genes in vivo. Testing miRNA function in mice is complicated by potential redundancy between family members. To circumvent this, we have developed protocols for introducing modified antisense oligonucleotides (antagomiRs)
in ovo
during chick development. Using this approach, we identify a layer of regulatory control provided by the miR-196 family in defining the boundary of Hox gene expression along the anterior-posterior (A-P) embryonic axis. Following knockdown of miR-196, we observe a homeotic transformation of the last cervical vertebrae toward a thoracic identity. This phenotypic alteration is, in part, due to an anterior expansion of
Hoxb8
gene expression and consolidates the in vivo relevance of post-transcriptional Hox gene regulation provided by miRNAs in the complex hierarchies governing axial pattering.
Applying an exemplar model to the artificial-grammar task: String completion and performance on individual items
Authors: Jamieson Randall K. , Mewhort D. J. K.
Published: October 2009

Jamieson and Mewhort (2009a) demonstrated that performance in the artificial-grammar task could be understood using an exemplar model of memory. We reinforce the position by testing the model against data for individual test items both in a standard artificial-grammar experiment and in a string-completion variant of the standard procedure. We argue that retrieval is sensitive to structure in memory. The work ties performance in the artificial-grammar task to principles of explicit memory.
Should Vascular Surgery Patients Be Screened Preoperatively for Methicillin-Resistant Staphylococcus aureus?
Authors: Lee Bruce Y. , Tsui Becky Y. , Bailey Rachel R. , Smith Kenneth J. , Muder Robert R. , Lewis G. Jonathan , Harrison Lee H.
Published: October 2009

Background.

Methicillin-resistant Staphylococcus aureus (MRSA) can cause severe infection in patients who are undergoing vascular surgical operations. Testing all vascular surgery patients preoperatively for MRSA and attempting to decolonize those who have positive results may be a strategy to prevent MRSA infection. The economic value of such a strategy has not yet been determined.

Methods.

We developed a decision-analytic computer simulation model to determine the economic value of using such a strategy before all vascular surgical procedures from the societal and third-party payer perspectives at different MRSA prevalence and decolonization success rates.

Results.

The model showed preoperative MRSA testing to be cost-effective (incremental cost-effectiveness ratio, <$50,000 per quality-adjusted life year) when the MRSA prevalence is ≥0.01 and the decolonization success rate is ≥0.25. In fact, this strategy was dominant (ie, less costly and more effective) at the following thresholds: MRSA prevalence ≥0.01 and decolonization success rate ≥0.5, and MRSA prevalence ≥0.025 and decolonization success rate ≥0.25.

Conclusion.

Testing and decolonizing patients for MRSA before vascular surgery may be a cost-effective strategy over a wide range of MRSA prevalence and decolonization success rates.
Tungsten accumulation in H-mode plasmas of JT-60U
Authors: Nakano T. , Asakura N. , Kubo H. , Yanagibayashi J. , Ueda Y.
Published: October 2009

It has been observed that with increasing toroidal rotation velocity inside the q = 1 layer in the direction opposite to the plasma current, sawtooth activity becomes moderate and tungsten accumulation becomes significant. The tungsten accumulation level is significantly reduced from this trend in the case when electron cyclotron wave or high energy neutral beam is injected into the plasma core. In contrast, the tungsten accumulation is kept high by the electron cyclotron wave injection into the peripheral region.
Radial transport of the nonthermal electrons in runaway discharges in the SINP tokamak from analysis of hard x-ray fluctuations
Authors: Hui A.K. , Saha S.K. , Chowdhury S. , Raychaudhuri Santwana , Banik D.
Published: October 2009

X-ray bursts from nonthermal electrons (∼10 keV to 1 MeV) emanating from the core plasma and the limiter are measured simultaneously in runaway dominated discharges in the SINP tokamak using a tangentially viewing NaI(Tl) detector and a detector that views the limiter areas. The radial transport coefficient of the nonthermal electrons has been derived from the cross-correlation function of the two x-ray intensities. Two phases of the plasma discharges with distinct transport of the nonthermal electrons are found in these experiments. The stochastic magnetic field fluctuations obtained from the transport coefficients are found to have a relationship with the autocorrelation functions of the x-ray emissivity signals.
Characteristics of momentum transport in JT-60U H-mode plasmas
Authors: Yoshida M. , Kamada Y. , Takenaga H. , Sakamoto Y. , Oyama N. , Urano H.
Published: October 2009

Properties of the toroidal momentum diffusivity (χϕ) and the convection velocity (V
conv) in JT-60U H-mode plasmas have been obtained by plasma parameter scans such as the plasma current, neutral beam heating power and electron density. The toroidal momentum diffusivity increases with increasing heat diffusivity (χi) over a wide range of radii (r/a = 0.2–0.6) and χϕ/χi ∼ 0.7–3 at the half radius (r/a = 0.5). The inward convection velocity (−V
conv) increases with increasing χϕ, and −V
conv/χϕ ∼ 0.5–2 (m−1) at r/a = 0.5. It is found that the ratio χϕ/χi increases with increasing ion temperature and decreases with increasing electron density. These tendencies are observed in other radial positions of r/a = 0.3, 0.4 and 0.6. Moreover, the ratio −V
conv/χϕ at r/a = 0.4, 0.5 and 0.6 increases with increasing ion and electron temperatures or temperature gradients.
Synthetic Lethal Genetic Interactions That Decrease Somatic Cell Proliferation in Caenorhabditis elegans Identify the Alternative RFCCTF18as a Candidate Cancer Drug Target
Authors: McLellan Jessica , O'Neil Nigel , Tarailo Sanja , Stoepel Jan , Bryan Jennifer , Rose Ann , Hieter Philip
Published: October 2009

Somatic mutations causing chromosome instability (CIN) in tumors can be exploited for selective killing of cancer cells by knockdown of second-site genes causing synthetic lethality. We tested and statistically validated synthetic lethal (SL) interactions between mutations in six Saccharomyces cerevisiae CIN genes orthologous to genes mutated in colon tumors and five additional CIN genes. To identify which SL interactions are conserved in higher organisms and represent potential chemotherapeutic targets, we developed an assay system in Caenorhabditis elegans to test genetic interactions causing synthetic proliferation defects in somatic cells. We made use of postembryonic RNA interference and the vulval cell lineage of C. elegans as a readout for somatic cell proliferation defects. We identified SL interactions between members of the cohesin complex and CTF4, RAD27, and components of the alternative RFCCTF18complex. The genetic interactions tested are highly conserved between S. cerevisiae and C. elegans and suggest that the alternative RFC components DCC1, CTF8, and CTF18 are ideal therapeutic targets because of their mild phenotype when knocked down singly in C. elegans . Furthermore, the C. elegans assay system will contribute to our knowledge of genetic interactions in a multicellular animal and is a powerful approach to identify new cancer therapeutic targets.
Seed-based IntaRNA prediction combined with GFP-reporter system identifies mRNA targets of the small RNA Yfr1
Authors: Richter Andreas S. , Schleberger Christian , Backofen Rolf , Steglich Claudia
Published: October 2009

Motivation:  Prochlorococcus possesses the smallest genome of all sequenced photoautotrophs. Although the number of regulatory proteins in the genome is very small, the relative number of small regulatory RNAs is comparable with that of other bacteria. The compact genome size of Prochlorococcus offers an ideal system to search for targets of small RNAs (sRNAs) and to refine existing target prediction algorithms.

Results: Target predictions for the cyanobacterial sRNA Yfr1 were carried out with INTARNA in Prochlorococcus MED4. The ultraconserved Yfr1 sequence motif was defined as the putative interaction seed. To study the impact of Yfr1 on its predicted mRNA targets, a reporter system based on green fluorescent protein (GFP) was applied. We show that Yfr1 inhibits the translation of two predicted targets. We used mutation analysis to confirm that Yfr1 directly regulates its targets by an antisense interaction sequestering the ribosome binding site, and to assess the importance of interaction site accessibility.

Contact:  backofen@informatik.uni-freiburg.de; claudia.steglich@biologie.uni-freiburg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Perspective on post-menopausal osteoporosis: establishing an interdisciplinary understanding of the sequence of events from the molecular level to whole bone fractures
Authors: McNamara L. M.
Published: October 2009

Current drug treatments for post-menopausal osteoporosis cannot eliminate bone fractures, possibly because the mechanisms responsible for bone loss are not fully understood. Although research within various disciplines has significantly advanced the state of knowledge, fundamental findings are not widely understood between different disciplines. For that reason, this paper presents noteworthy experimental findings from discrete disciplines focusing on post-menopausal osteoporosis. These studies have established that, in addition to bone loss, significant changes in bone micro-architecture, tissue composition and micro-damage occur. Cellular processes and molecular signalling pathways governing pathological bone resorption have been identified to a certain extent. Ongoing studies endeavour to determine how such changes are initiated at the onset of oestrogen deficiency. It emerges that, because of the discrete nature of previous research studies, the sequence of events that lead to bone fracture is not fully understood. In this paper, two sequences of multi-scale changes are proposed and the experimental challenges that need to be overcome to fully define this sequence are outlined. Future studies must comprehensively characterize the time sequence of molecular-, cellular- and tissue-level changes to attain a coherent understanding of the events that ultimately lead to bone fracture and inform the future development of treatments for post-menopausal osteoporosis.
On the Lagrangian optimization of wall-injected flows: from the Hart–McClure potential to the Taylor–Culick rotational motion
Authors: Saad Tony , Majdalani Joseph
Published: October 2009

The Taylor–Culick solution for a porous cylinder is often used to describe the bulk gas motion in idealized representations of solid rocket motors. However, other approximate solutions may be found that satisfy the same fundamental constraints. In this vein, steeper or smoother profiles may be observed in either experimental or numerical tests, particularly in the presence of intense levels of acoustic energy. In this study, we use the Lagrangian optimization principle to arrive at multiple solutions that can help to explain the practically observed motions. We then search for the extreme states that display either the least or the most kinetic energy. These are derived and found to be dependent on the chamber’s aspect ratio. By assuming a slender case, simple expressions are retrieved from which both the rotational Taylor–Culick and the irrotational Hart–McClure solutions are recovered as special cases. At the outset, a new family of flow approximations is derived extending from purely potential to highly rotational fields. These are constructed, verified and catalogued based on their kinetic energies. To help understand the tendency of a motion to shift energy states, a second law analysis is performed and used to rank these solutions based on their entropy content. Interestingly, the Taylor–Culick profile is found to represent an equilibrium state entailing the most energy and entropy among those starting from the rest. A formal extension of Kelvin’s minimum energy theorem to an open region is then pursued, followed by a direct implementation to the problem at hand. Three other flow motions with open boundaries are examined to further exemplify the application of Kelvin’s extended criteria. Our efforts illustrate the overarching harmony that exists between Lagrange’s minimization principle and Kelvin’s minimum energy theorem; both converge on the potential solution as the least kinetic energy bearer even when the velocity at the open barrier is finite.
Re-evaluating the costs and limits of adaptive phenotypic plasticity
Authors: Auld Josh R. , Agrawal Anurag A. , Relyea Rick A.
Published: October 2009

When the optimal phenotype differs among environments, adaptive phenotypic plasticity can evolve unless constraints impede such evolution. Costs and limits of plasticity have been proposed as important constraints on the evolution of plasticity, yet confusion exists over their distinction. We attempt to clarify these concepts by reviewing their categorization and measurement, highlighting how costs and limits are defined in different currencies (and may describe the same phenomenon). Conclusions from studies that measure the costs of plasticity have been equivocal, but we caution that these conclusions may be premature owing to a potentially common correlation between environment-specific trait values and the magnitude of trait plasticities (i.e. multi-collinearity) that results in imprecise and/or biased estimates of the costs. Meanwhile, our understanding of the limits of plasticity, and how they may be underlain by the costs of plasticity, is still in its infancy. Based on our re-evaluation of these constraints, we discuss areas for future research.
History-dependent properties of skeletal muscle myofibrils contracting along the ascending limb of the force–length relationship
Authors: Pun Clara , Syed Ali , Rassier Dilson E.
Published: October 2009

There is a history dependence of skeletal muscle contraction: stretching activated muscles induces a long-lasting force enhancement, while shortening activated muscles induces a long-lasting force depression. These history-dependent properties cannot be explained by the current model of muscle contraction, and its mechanism is unknown. The purposes of this study were (i) to evaluate if force enhancement and force depression are present at short lengths (the ascending limb of the force–length (FL) relationship), (ii) to evaluate if the history-dependent properties are associated with sarcomere length (SL) non-uniformity and (iii) to determine the effects of cross-bridge (de)activation on force depression. Rabbit psoas myofibrils were isolated and attached between two microneedles for force measurements. Images of the myofibrils were projected onto a linear photodiode array for measurements of SL. Myofibrils were activated by either Ca2+or MgADP; the latter induces cross-bridge attachment to actin independently of Ca2+. Activated myofibrils were subjected to three stretches or shortenings (approx. 4% SL at approx. 0.07 µm s−1sarcomere−1) along the ascending limb of the FL relationship separated by periods (approx. 5 s) of isometric contraction. Force after stretch was higher than force after shortening at similar SLs. The differences in force could not be explained by SL non-uniformity. The FL relationship produced by Ca2+- and MgADP-activated myofibrils were similar in stretch experiments, but after shortening MgADP activation produced forces that were higher than Ca2+activation. Since MgADP induces the formation of strongly bound cross-bridges, this result suggests that force depression following shortening is associated with cross-bridge deactivation.
Post-glacial redistribution and shifts in productivity of giant kelp forests
Authors: Graham Michael H. , Kinlan Brian P. , Grosberg Richard K.
Published: October 2009

Quaternary glacial–interglacial cycles create lasting biogeographic, demographic and genetic effects on ecosystems, yet the ecological effects of ice ages on benthic marine communities are unknown. We analysed long-term datasets to develop a niche-based model of southern Californian giant kelp (
Macrocystis pyrifera
) forest distribution as a function of oceanography and geomorphology, and synthesized palaeo-oceanographic records to show that late Quaternary climate change probably drove high millennial variability in the distribution and productivity of this foundation species. Our predictions suggest that kelp forest biomass increased up to threefold from the glacial maximum to the mid-Holocene, then rapidly declined by 40–70 per cent to present levels. The peak in kelp forest productivity would have coincided with the earliest coastal archaeological sites in the New World. Similar late Quaternary changes in kelp forest distribution and productivity probably occurred in coastal upwelling systems along active continental margins worldwide, which would have resulted in complex shifts in the relative productivity of terrestrial and marine components of coastal ecosystems.
High-resolution nucleosome mapping reveals transcription-dependent promoter packaging
Authors: Weiner Assaf , Hughes Amanda , Yassour Moran , Rando Oliver J. , Friedman Nir
Published: October 2009

Genome-wide mapping of nucleosomes has revealed a great deal about the relationships between chromatin structure and control of gene expression, and has led to mechanistic hypotheses regarding the rules by which chromatin structure is established. High-throughput sequencing has recently become the technology of choice for chromatin mapping studies, yet analysis of these experiments is still in its infancy. Here, we introduce a pipeline for analyzing deep sequencing maps of chromatin structure and apply it to data from S. cerevisiae. We analyze a digestion series where nucleosomes are isolated from under- and overdigested chromatin. We find that certain classes of nucleosomes are unusually susceptible or resistant to overdigestion, with promoter nucleosomes easily digested and mid-coding region nucleosomes being quite stable. We find evidence for highly sensitive nucleosomes located within “nucleosome-free regions,” suggesting that these regions are not always completely naked but instead are likely associated with easily digested nucleosomes. Finally, since RNA polymerase is the dominant energy-consuming machine that operates on the chromatin template, we analyze changes in chromatin structure when RNA polymerase is inactivated via a temperature-sensitive mutation. We find evidence that RNA polymerase plays a role in nucleosome eviction at promoters and is also responsible for retrograde shifts in nucleosomes during transcription. Loss of RNA polymerase results in a relaxation of chromatin structure to more closely match in vitro nucleosome positioning preferences. Together, these results provide analytical tools and experimental guidance for nucleosome mapping experiments, and help disentangle the interlinked processes of transcription and chromatin packaging.
Systematic review: portal vein thrombosis in cirrhosis
Authors: TSOCHATZIS E. A. , SENZOLO M. , GERMANI G. , GATT A. , BURROUGHS A. K.
Published: October 2009

Aliment Pharmacol Ther 31, 366‐374

Background  As current imaging techniques in cirrhosis allow detection of asymptomatic portal vein thrombosis during routine ultrasonography, more patients with cirrhosis are diagnosed with portal vein thrombosis. Although a consensus on noncirrhotic extra‐hepatic portal vein thrombosis has been published, no such consensus exists for portal vein thrombosis with cirrhosis.

Aim  To perform a systematic review of nonmalignant portal vein thrombosis in cirrhosis in terms of prevalence, pathogenesis, diagnosis, clinical course and management.

Methods  Studies were identified by a search strategy using MEDLINE and EMBASE.

Results  Portal vein thrombosis is encountered in 10–25% of cirrhotics. In terms of pathophysiology, cirrhosis is no longer considered a hypocoagulable state; rather than a bleeding risk in cirrhosis, various clinical studies support a thrombotic potential. Clinical findings of portal vein thrombosis in cirrhosis vary from asymptomatic disease to a life‐threatening condition at first presentation. Optimal management of portal vein thrombosis in cirrhosis is currently not addressed in any consensus publication. Treatment strategies most often include the use of anticoagulation, while thrombectomy and transjugular intrahepatic portosystemic shunts are considered second‐line options.

Conclusions  Portal vein thrombosis in cirrhosis has many unresolved issues, which are often the critical problems clinicians encounter in their everyday practice. We propose a possible research agenda to address these unresolved issues.
Cell cycle and tissue of origin contribute to the migratory behaviour of human fetal and adult mesenchymal stromal cells
Authors: Maijenburg Marijke W. , Noort Willy A. , Kleijer Marion , Kompier Charlotte J. A. , Weijer Kees , Van Buul Jaap D. , Van Der Schoot C. Ellen , Voermans Carlijn
Published: October 2009

Mesenchymal stromal cells (MSC) are potential cells for cellular therapies, in which the recruitment and migration of MSC towards injured tissue is crucial. Our data show that culture‐expanded MSC from fetal lung and bone marrow, adult bone marrow and adipose tissue contained a small percentage of migrating cells in vitro, but the optimal stimulus was different. Overall, fetal lung‐MSC had the highest migratory capacity. As fetal bone marrow‐MSC had lower migratory potential than fetal lung‐MSC, the tissue of origin may determine the migratory capacity of MSC. No additive effect in migration towards combined stimuli was observed, which suggests only one migratory MSC fraction. Interestingly, actin rearrangement and increased paxillin phosphorylation were observed in most MSC upon stromal cell‐derived factor‐1α or platelet‐derived growth factor‐BB stimulation, indicating that this mechanism involved in responding to migratory cues is not restricted to migratory MSC. Migratory MSC maintained differentiation and migration potential, and contained significantly less cells in S‐ and G2/M‐phase than their non‐migrating counterpart. In conclusion, our results suggest that MSC from various sources have different migratory capacities, depending on the tissue of origin. Similar to haematopoietic stem cells, cell cycle contributes to MSC migration, which offers perspectives for modulation of MSC to enhance efficacy of future cellular therapies.
Clopidogrel: mechanisms of action and review of the evidence relating to use during skin surgery procedures
Authors: Stewart L. C. , Langtry J. A. A.
Published: October 2009

Patients who have skin surgery may be taking medication that increases the likelihood of bleeding, such as clopidogrel, aspirin, warfarin, heparin and nonsteroidal anti-inflammatory drugs (NSAIDS). All of these may increase the risk of perioperative and postoperative bleeding. This article examines the mechanism of action of clopidogrel, current practice, and evidence for or against continuing its use during skin surgery. The mechanisms of action of aspirin, warfarin, heparin and NSAIDS will also be briefly discussed.
Supraciliary wrinkles and botulinum toxin A
Authors: Ghalamkarpour F. , Robati R. M. , Aryanejad F. , Toossi P.
Published: October 2009

Background. Injection of botulinum toxin into certain areas of face that carry a high risk of ptosis (danger zone) needs caution in application. An example is the lateral forehead, particularly the lower portion.

Aim. In this study, we evaluated the efficacy and safety of treating supraciliary wrinkles in the lower lateral forehead by injections of botulinum toxin at the temporal hairline, keeping a reasonable distance from danger zone.

Methods. In this randomized clinical trial, 40 women (mean age 35 years) were selected and divided into two groups, A and B. both groups were treated with botulinum toxin to treat wrinkles in the frown area, as well as frontal lines and lateral canthus lines. Group B received extra injections at each temporal line for treatment of supraciliary wrinkles.

Results. There was a significant difference in total wrinkle number and mean number of wrinkles between the two groups after injections (paired t-test, P < 0.01). No ptosis was seen in either group.

Conclusions. Injection of botulinum toxin type A through the temporal hairline to correct supraciliary wrinkles seems to be safe and effective.