bluuebunny/crossref_metadata_2025 huggingface dataset:
Simple experimental method for alpha particle range determination in lead iodide films
Authors: Dmitriev Yuri , Bennett Paul R. , Cirignano Leonard J. , Klugerman Mikhail , Shah Kanai S.
Published: June 2007

An experimental method for determining the range of alpha particles in films based on I-Vs analysis has been suggested. The range of 5.5MeV alpha particles in PbI2 films determined by this technique is 30±5μm, and this value is in agreement with the value calculated by SRIM (the stopping and range of ions in matter), r=24μm in PbI2. More than 100 I-Vs of PbI2 films with different thicknesses and quality have been analyzed, and the influence of alpha particle radiation on PbI2 I-Vs curves has been studied. Developed analytical methods (dependence of current density on electric field and conception of surface defects) were used, and the method limitations are discussed. It was shown that I-Vs demonstrate the tendency to obey Ohm’s law under alpha radiation. On the other hand, dark conductivity of the lead iodide films shows a typical impure character that can lead to an overestimation of the alpha particles’ range in PbI2 films. After films were exposed to alpha radiation, the dark resistivity and I-V shape of some films improved. Also, a weak decrease of the charge carrier concentration, due to a decrease of the “surface defect” concentration (“surface refining”), was registered after successive measurements of I-Vs.
Dissociation of carbonic acid: Gas phase energetics and mechanism from ab initio metadynamics simulations
Authors: Kumar P. Padma , Kalinichev Andrey G. , Kirkpatrick R. James
Published: June 2007

A comprehensive metadynamics study of the energetics, stability, conformational changes, and mechanism of dissociation of gas phase carbonic acid, H2CO3, yields significant new insight into these reactions. The equilibrium geometries, vibrational frequencies, and conformer energies calculated using the density functional theory are in good agreement with the previous theoretical predictions. At 315K, the cis-cis conformer has a very short life time and transforms easily to the cis-trans conformer through a change in the OC–O–H dihedral angle. The energy difference between the trans-trans and cis-trans conformers is very small (≈1kcal∕mol), but the trans-trans conformer is resistant to dissociation to carbon dioxide and water. The cis-trans conformer has a relatively short path for one of its hydroxyl groups to accept the proton from the other end of the molecule, resulting in a lower activation barrier for dissociation. Comparison of the free and potential energies of dissociation shows that the entropic contribution to the dissociation energy is less than 10%. The potential energy barrier for dissociation of H2CO3 to CO2 and H2O from the metadynamics calculations is 5–6kcal∕mol lower than in previous 0K studies, possibly due to a combination of a finite temperature and more efficient sampling of the energy landscape in the metadynamics calculations. Gas phase carbonic acid dissociation is triggered by the dehydroxylation of one of the hydroxyl groups, which reorients as it approaches the proton on the other end of the molecule, thus facilitating a favorable H–O–H angle for the formation of a product H2O molecule. The major atomic reorganization of the other part of the molecule is a gradual straightening of the OCO bond. The metadynamics results provide a basis for future simulation of the more challenging carbonic acid-water system.
Dispersion interactions within the Piris natural orbital functional theory: The helium dimer
Authors: Piris M. , Lopez X. , Ugalde J. M.
Published: June 2007

The authors have investigated the description of the dispersion interaction within the Piris natural orbital functional (PNOF) theory. The PNOF arises from an explicit antisymmetric approach for the two-particle cumulant in terms of two symmetric matrices, Δ and Λ. The functional forms of these matrices are obtained from the generalization of the two-particle system expressions, except for the off-diagonal elements of Δ. The mean value theorem and the partial sum rule obtained for the off-diagonal elements of Δ provide a prescription for deriving practical functionals. In particular, the previous employed approximation {Jpp∕2} for the mean values {Jp*} affords several molecular properties but it is incapable to account for dispersion effects. In this work, the authors analyze a new approach for Jp* obtained by factorization of the matrix Δ within the bounds on its off-diagonal elements imposed by the positivity conditions of the two-particle reduced density matrix. Additional terms for the matrix elements of Λ proportional to the square root of the holes are again introduced to describe properly the occupation numbers of the lowest occupied levels. The authors have found that the cross products between weakly occupied orbitals must be removed from the functional form of Λ to obtain a correct long-range asymptotic behavior. The PNOF is used to predict the binding energy as well as the equilibrium distance of the helium dimer. The results are compared with the full configuration-interaction calculations and the corresponding experimental data.
Contactless electroreflectance investigation of energy levels in a 1.3μm emitting laser structure with the gain medium composed of InAsN quantum dots embedded in GaInNAs∕GaAs quantum wells
Authors: Motyka M. , Kudrawiec R. , Sęk G. , Misiewicz J. , Bisping D. , Marquardt B. , Forchel A. , Fischer M.
Published: June 2007

Laser structures designed for the emission at 1.3μm and based on an active region containing InAsN quantum dots (QDs) embedded in GaInNAs∕GaAs quantum wells (QWs) have been investigated by contactless electroreflectance. Optical transitions related to both the dots and the wells have been observed and the energies of the latter have been calculated using the effective mass approach. It has been shown that QW confines one electron, one light-hole, and three heavy-hole states only and the energy separation between the QD and QW ground state transitions is approximately 250meV, which is ten times higher than the thermal energy at room temperature.
Investigation of point defect generation in dry etched InP ridge waveguide structures
Authors: Avella M. , Jiménez J. , Pommereau F. , Landesman J. P. , Rhallabi A.
Published: June 2007

Waveguides engraved in InP by dry etching, reactive ion etching and inductively coupled plasma (ICP), were studied by cathodoluminescence. The dry etching processes were found to induce nonradiative recombination centers, which reduce the luminescence emission from the ridge structures. In addition, the ICP process introduced intrinsic defects, probably In vacancy related defects, which were generated at the dielectric cap/InP interface at the ridge top.
Density functional approach to the adsorption of spherical molecules on a surface modified with attached short chains
Authors: Borówko M. , Rżysko W. , Sokołowski S. , Staszewski T.
Published: June 2007

A density functional and Monte Carlo simulation study of end-grafted polymers immersed by simple fluids is presented. The polymer molecules are modeled as freely jointed tangent hard spheres with the end segments linked to the surface. The authors analyze an influence of the chain length, the grafting density, and a nature of solvent on the brush structure. Adsorption of hard-sphere mixtures on the modified surface is also discussed. The theory precisely approximates simulation data.
Ab Initio atomic simulations of antisite pair recovery in cubic silicon carbide
Authors: Gao F. , Du J. , Bylaska E. J. , Posselt M. , Weber W. J.
Published: June 2007

The thermal stability of an antisite pair in cubic silicon carbide (3C-SiC) is studied using ab initio molecular dynamics within the framework of density functional theory. The lifetime of the antisite pair configuration is calculated for temperatures between 1800 and 2250K, and the effective activation energy for antisite pair recombination is determined to be 2.52eV. The recombination energy path and static energy barrier are also calculated using the nudged elastic band method along with the dimer method to accurately locate the transition states. The consistency of the results suggests that the antisite pair cannot be correlated with the DI photoluminescence center, as proposed previously by theoretical interpretations. An extended exchange mechanism is found for the antisite pair recombination.
Fast radiative quantum dots: From single to multiple photon emission
Authors: Peter E. , Laurent S. , Bloch J. , Hours J. , Varoutsis S. , Robert-Philip I. , Beveratos A. , Lemaître A. , Cavanna A. , Patriarche G. , Senellart P. , Martrou D.
Published: June 2007

Photon correlation measurements are performed on single GaAs quantum dots with various excitonic radiative lifetimes. A continuous increase of the probability that the quantum dot emits more than one photon per excitation pulse is observed when decreasing the exciton radiative lifetime. The authors show that this increase is due to recapture processes into the quantum dot. A model for the second-order autocorrelation function including relaxation processes is developed and gives good description of the experimental observations.
Low threshold, high gain AlGaInAs quantum dot lasers
Authors: Schlereth T. W. , Schneider C. , Kaiser W. , Höfling S. , Forchel A.
Published: June 2007

The properties of AlGaInAs quantum dot (QD) lasers are reported and compared to GaInAs QD lasers emitting at a similar wavelength (∼920nm). It is found that Al0.15Ga0.23In0.62As QD lasers show an ∼2.1 times higher material gain and lower threshold current densities than Ga0.57In0.43As lasers (a factor of ∼1.4 for 1.0mm long and 100μm wide devices). Both laser samples display comparable high internal quantum efficiencies of 0.79 (AlGaInAs) and 0.83 (GaInAs). The AlGaInAs devices exhibit a high characteristic temperature of 174K between 15 and 85°C.
Plasma based platinum nanoaggregates deposited on carbon nanofibers improve fuel cell efficiency
Authors: Caillard Amaël , Charles Christine , Boswell Rod , Brault Pascal , Coutanceau Christophe
Published: June 2007

Improved platinum catalytic utilization has been achieved by creating an open support structure based on aligned carbon nanofibers (CNFs) attached to carbon loaded carbon cloth electrodes [known as gas diffusion layer (GDL)]. The nickel catalyst used to initiate the CNFs growth; the CNFs themselves and the 5nm Pt nanoaggregates were deposited sequentially in the same low pressure plasma reactor. This oriented catalyst structure was incorporated into a membrane electrode assembly and tested with and without CNFs and on carbon paper or GDL. The performance of the fuel cells based on CNFs and GDL was better over the entire range of operating current.
Temperature- and magnetic-field-induced phase transitions in Fe-rich FePt alloys
Authors: Rong Chuan-Bing , Liu J. Ping
Published: June 2007

Structural and magnetic properties of the FexPt100−x (x=78–88) alloys have been investigated. It is found that for all of the investigated compositions, a phase transition occurs from the disordered γ phase to the ordered α phase during cooling, while a reverse process takes place during heating. Moreover, magnetic fields also induce a phase transition from the γ phase to the α phase near the transition temperature. The temperature- and magnetic-field-induced phase transitions give rise to a huge negative thermal expansion and thus a giant magnetic entropy change (up to 39.8J∕kgK for the alloy with x=79). The contribution of the magnetic field induced phase transition to the total magnetic entropy change is estimated to be around 20%–25%.
Correction for longitudinal mode vibration in thin slender beams
Authors: Liang Cai , Morshed Shakib , Prorok Barton C.
Published: June 2007

This letter reports on a correction to the theoretical prediction of longitudinal mode vibration in thin, slender beams. Thin magnetostrictive strips were fashioned from Metglas™ and subjected to a modulated magnetic field to determine resonant frequency and acoustic wave propagation speed. The results indicated that current analytical solutions were not adequate to predict behavior. Numerical simulations were performed that adjusted Poisson’s ratio until the acoustic wave speed matched that measured in the experiments. The results indicated that the current equations, formulated using the plane-strain modulus, should be modified by using the plane-stress or biaxial modulus.
Elementary building blocks of graphene-nanoribbon-based electronic devices
Authors: Xu Zhiping , Zheng Quan-Shui , Chen Guanhua
Published: June 2007

Graphene nanoribbon junction based electronic devices are proposed in this letter. Nonequilibrium Green’s function calculations show that nanoribbon junctions tailored from single layer graphene with different edge shapes and widths can act as metal/semiconductor junctions and quantum dots can be implemented. In virtue of the possibilities of patterning monolayer graphene down to atomic precision, these structures, quite different from the previously reported two-dimensional bulk graphene or carbon nanotube devices, are expected to be used as the building blocks of the future nanoelectronics.
Effects of hydrogenated annealing on structural defects, conductivity, and magnetic properties of V-doped ZnO powders
Authors: Liu S. H. , Hsu H. S. , Lin C. R. , Lue C. S. , Huang J. C. A.
Published: June 2007

The structure, electrical property, and magnetism of 7.5% V-doped ZnO powders that were hydrogenated annealed at 300, 500, and 700°C have been systematically investigated. The saturation magnetization and conductivity of the V:ZnO powders increase with hydrogenated annealing temperature (Tha), and the magnetization-temperature curves transform from paramagnetism to weak ferromagnetism (∼10−4μB∕V atom) as Tha increases. The results suggest that ferromagnetism in V:ZnO powders is highly correlated to the structural defects.
Downregulation of neutral invertase activity in sugarcane cell suspension cultures leads to a reduction in respiration and growth and an increase in sucrose accumulation
Authors: Rossouw Debra , Bosch Sue , Kossmann Jens , Botha Frederik C. , Groenewald Jan-Hendrik
Published: June 2007

Suspension cultures were used as a model system to investigate sucrose metabolism in four sugarcane (Saccharum spp. interspecific hybrids) cell lines transformed with antisense neutral invertase (NI) constructs. Throughout a 14-day growth cycle two cell lines in which the antisense sequence was under the control of a tandem CaMV-35S: maize ubiquitin promoter showed a strong reduction in NI activity, as well as reduced hexose and increased sucrose concentrations in comparison to the control line. In lines where the antisense NI sequence was under the control of the weaker CaMV-35S promoter alone, changes in enzyme activity and sugar concentrations were intermediate to those of the more strongly inhibited lines and the control. In comparison to the control line, a higher sucrose to hexose ratio, i.e. increased purity, was obtained in all the lines with reduced NI activity. The in vivo rate of sucrose hydrolysis was reduced in the transgenic lines, suggesting a concomitant reduction in the flux through the ‘futile cycle’ of sucrose breakdown and re-synthesis. Differences between the transgenic cultures and the control were most pronounced during the early stages of the growth cycle and tapered off as the cultures matured. The transgenic cultures displayed impaired growth characteristics suggesting that the growth rate of these cells was retarded because of the reduced availability of hexoses for respiration.
Regulation of invertase: a 'suite' of transcriptional and post-transcriptional mechanisms
Authors: Huang Li-Fen , Bocock Philip N. , Davis John M. , Koch Karen E.
Published: June 2007

Recent evidence indicates that several mechanisms can alter invertase activity and, thus, affect sucrose metabolism and resource allocation in plants. One of these mechanisms is the compartmentalisation of at least some vacuolar invertases in precursor protease vesicles (PPV), where their retention could control timing of delivery to vacuoles and hence activity. PPV are small, ER-derived bodies that sequester a subset of vacuolar-bound proteins (such as invertases and protease precursors) releasing them to acid vacuoles in response to developmental or environmental signals. Another newly-identified effector of invertases is wall-associated kinase 2 (WAK2), which can regulate a specific vacuolar invertase in Arabidopsis (AtvacINV1) and alter root growth when osmolyte supplies are limiting. WAKs are ideally positioned to sense changes in the interface between the cell wall and plasma membrane (such as turgor), because the N-terminus of each WAK extends into the cell wall matrix (where a pectin association is hypothesised) and the C-terminus has a cytoplasmic serine/threonine kinase domain (signalling). Still other avenues of invertase control are provided by a diverse group of kinases and phosphatases, consistent with input from multiple sensing systems for sugars, pathogens, ABA and other hormones. Mechanisms of regulation may also vary for the contrasting sugar responses of different acid invertase transcripts. Some degree of hexokinase involvement and distinctive kinetics have been observed for the sugar-repressed invertases, but not for the more common, sugar-induced forms examined thus far. An additional means of regulation for invertase gene expression lies in the multiple DST (Down STream) elements of the 3′ untranslated region for the most rapidly repressed invertases. Similar sequences were initially identified in small auxin-up RNAs (SAUR) where they mediate rapid mRNA turnover. Finally, the invertase inhibitors, cell wall- and vacuolar inhibitors of fructosidase (CIF and VIF, respectively) are indistinguishable by sequence alone from pectin methylesterase inhibitors (PMEI); however, recent evidence suggests binding specificity may be determined by flexibility of a short, N-terminal region. These recently characterised processes increase the suite of regulatory mechanisms by which invertase – and, thus, sucrose metabolism and resource partitioning – can be altered in plants.
Multilevel genomics analysis of carbon signalling during low carbon availability: coordinating the supply and utilisation of carbon in a fluctuating environment
Authors: Stitt Mark , Gibon Yves , Lunn John E. , Piques Maria
Published: June 2007

Plants alternate between a net surplus of carbon in the light and a net deficit at night. This is buffered by accumulating starch in the light and degrading it at night. Enough starch is accumulated to support degradation throughout the night, with a small amount remaining at the end of the 24-h diurnal cycle. This review discusses how this balance between the supply and utilisation of carbon is achieved in Arabidopsis. It is important to regulate starch turnover to avoid an acute carbon deficiency. A 2–4 h extension of the night leads to exhaustion of starch, a collapse of sugars, a switch from biosynthesis to catabolism and an acute inhibition of growth by low carbon, which is not immediately reversed when carbon becomes available again. In starchless pgm mutants, where sugars are depleted each night, this leads to a recurring inhibition of growth that is not reversed until 5–6 h into the following light period. Several lines of evidence show that starch accumulation is regulated in response to events that are initiated during periods of low carbon. Starch accumulation is decreased when small amounts of sucrose are included in the growth medium. Sets of sugar-responsive genes were identified by supplying sugars to carbon-starved seedlings, or by illuminating 5-week-old plants in the presence of 350 or 50 ppm [CO2]. Almost all of these genes show large diurnal changes in starchless pgm mutants, which are driven by the depletion of carbon during the night. Many show significant diurnal changes in wild type plants, showing that ‘anticipatory’ changes in signalling pathways occur before acute carbon limitation develops. However, these diurnal changes of transcripts do not lead to immediate changes of enzyme activities. Whereas an extension of the night leads to major changes of transcripts within 4–6 h, changes in enzyme activities require several days. In pgm, enzyme activities and the levels of >150 metabolites resemble those found in wild type plants after several days in the dark. It is concluded that diurnal changes in transcript levels are integrated, over days, as changes in the levels of enzymes. We hypothesise that this facilitates an adjustment of metabolism to a mid-term shift in the conditions, while ignoring noise due to diurnal changes and day-to-day fluctuations. The rapid adjustment of starch synthesis after a period of acute carbon depletion is a consequence of the transient inhibition of growth. This leads to accumulation of sugars when carbon becomes available again, which triggers a large increase in trehalose-6-phosphate. This signal metabolite promotes thioredoxin-dependent post-translational activation of ADP glucose pyrophosphorylase. Mid-term acclimation to a decreased carbon supply may be mediated by a combination of post-translational regulation, longer-term changes in enzyme activities, and a decrease in the rate of growth.
Kinetics and thermodynamics of amyloid formation from direct measurements of fluctuations in fibril mass
Authors: Knowles Tuomas P. J. , Shu Wenmiao , Devlin Glyn L. , Meehan Sarah , Auer Stefan , Dobson Christopher M. , Welland Mark E.
Published: June 2007

Aggregation of proteins and peptides is a widespread and much-studied problem, with serious implications in contexts ranging from biotechnology to human disease. An understanding of the proliferation of such aggregates under specific conditions requires a quantitative knowledge of the kinetics and thermodynamics of their formation; measurements that to date have remained elusive. Here, we show that precise determination of the growth rates of ordered protein aggregates such as amyloid fibrils can be achieved through real–time monitoring, using a quartz crystal oscillator, of the changes in the numbers of molecules in the fibrils from variations in their masses. We show further that this approach allows the effect of other molecular species on fibril growth to be characterized quantitatively. This method is widely applicable, and we illustrate its power by exploring the free-energy landscape associated with the conversion of the protein insulin to its amyloid form and elucidate the role of a chemical chaperone and a small heat shock protein in inhibiting the aggregation reaction.
Bayesian modelling of shared gene function
Authors: Sykacek P. , Clarkson R. , Print C. , Furlong R. , Micklem G.
Published: June 2007

Motivation: Biological assays are often carried out on tissues that contain many cell lineages and active pathways. Microarray data produced using such material therefore reflect superimpositions of biological processes. Analysing such data for shared gene function by means of well-matched assays may help to provide a better focus on specific cell types and processes. The identification of genes that behave similarly in different biological systems also has the potential to reveal new insights into preserved biological mechanisms.

Results: In this article, we propose a hierarchical Bayesian model allowing integrated analysis of several microarray data sets for shared gene function. Each gene is associated with an indicator variable that selects whether binary class labels are predicted from expression values or by a classifier which is common to all genes. Each indicator selects the component models for all involved data sets simultaneously. A quantitative measure of shared gene function is obtained by inferring a probability measure over these indicators.

Through experiments on synthetic data, we illustrate potential advantages of this Bayesian approach over a standard method. A shared analysis of matched microarray experiments covering (a) a cycle of mouse mammary gland development and (b) the process of in vitro endothelial cell apoptosis is proposed as a biological gold standard. Several useful sanity checks are introduced during data analysis, and we confirm the prior biological belief that shared apoptosis events occur in both systems. We conclude that a Bayesian analysis for shared gene function has the potential to reveal new biological insights, unobtainable by other means.

Availability: An online supplement and MatLab code are available at http://www.sykacek.net/research.html#mcabf

Contact:  peter@sykacek.net

Supplementary information: Supplementary data are available at Bioinformatics online.
Statistical assessment of functional categories of genes deregulated in pathological conditions by using microarray data
Authors: Maglietta R. , Piepoli A. , Catalano D. , Licciulli F. , Carella M. , Liuni S. , Pesole G. , Perri F. , Ancona N.
Published: June 2007

Motivation: A major challenge in current biomedical research is the identification of cellular processes deregulated in a given pathology through the analysis of gene expression profiles. To this end, predefined lists of genes, coding specific functions, are compared with a list of genes ordered according to their values of differential expression measured by suitable univariate statistics.

Results: We propose a statistically well-founded method for measuring the relevance of predefined lists of genes and for assessing their statistical significance starting from their raw expression levels as recorded on the microarray. We use prediction accuracy as a measure of relevance of the list. The rationale is that a functional category, coded through a list of genes, is perturbed in a given pathology if it is possible to correctly predict the occurrence of the disease in new subjects on the basis of the expression levels of the genes belonging to the list only. The accuracy is estimated with multiple random validation strategy and its statistical significance is assessed against a couple of null hypothesis, by using two independent permutation tests. The utility of the proposed methodology is illustrated by analyzing the relevance of Gene Ontology terms belonging to biological process category in colon and prostate cancer, by using three different microarray data sets and by comparing it with current approaches.

Availability: Source code for the algorithms is available from author upon request.

Contact:  ancona@ba.issia.cnr.it

Supplementary information: Colon cancer data set and a complete description of experimental results are available at: ftp://bioftp:76bioftpxxx@marx.ba.issia.cnr.it/supp-info.htm
Total ancestry measure: quantifying the similarity in tree-like classification, with genomic applications
Authors: Yu Haiyuan , Jansen Ronald , Stolovitzky Gustavo , Gerstein Mark
Published: June 2007

Motivation: Many classifications of protein function such as Gene Ontology (GO) are organized in directed acyclic graph (DAG) structures. In these classifications, the proteins are terminal leaf nodes; the categories ‘above’ them are functional annotations at various levels of specialization and the computation of a numerical measure of relatedness between two arbitrary proteins is an important proteomics problem. Moreover, analogous problems are important in other contexts in large-scale information organization—e.g. the Wikipedia online encyclopedia and the Yahoo and DMOZ web page classification schemes.

Results: Here we develop a simple probabilistic approach for computing this relatedness quantity, which we call the total ancestry method. Our measure is based on counting the number of leaf nodes that share exactly the same set of ‘higher up’ category nodes in comparison to the total number of classified pairs (i.e. the chance for the same total ancestry). We show such a measure is associated with a power-law distribution, allowing for the quick assessment of the statistical significance of shared functional annotations. We formally compare it with other quantitative functional similarity measures (such as, shortest path within a DAG, lowest common ancestor shared and Azuaje's information-theoretic similarity) and provide concrete metrics to assess differences. Finally, we provide a practical implementation for our total ancestry measure for GO and the MIPS functional catalog and give two applications of it in specific functional genomics contexts.

Availability: The implementations and results are available through our supplementary website at: http://gersteinlab.org/proj/funcsim

Contact:  mark.gerstein@yale.edu

Supplementary information: Supplementary data are available at Bioinformatics online.
Advances in signaling in vertebrate regeneration as a prelude to regenerative medicine
Authors: Stoick-Cooper Cristi L. , Moon Randall T. , Weidinger Gilbert
Published: June 2007

While all animals have evolved strategies to respond to injury and disease, their ability to functionally recover from loss of or damage to organs or appendages varies widely damage to skeletal muscle, but, unlike amphibians and fish, they fail to regenerate heart, lens, retina, or appendages. The relatively young field of regenerative medicine strives to develop therapies aimed at improving regenerative processes in humans and is predicated on >40 years of success with bone marrow transplants. Further progress will be accelerated by implementing knowledge about the molecular mechanisms that regulate regenerative processes in model organisms that naturally possess the ability to regenerate organs and/or appendages. In this review we summarize the current knowledge about the signaling pathways that regulate regeneration of amphibian and fish appendages, fish heart, and mammalian liver and skeletal muscle. While the cellular mechanisms and the cell types involved in regeneration of these systems vary widely, it is evident that shared signals are involved in tissue regeneration. Signals provided by the immune system appear to act as triggers of many regenerative processes. Subsequently, pathways that are best known for their importance in regulating embryonic development, in particular fibroblast growth factor (FGF) and Wnt/β-catenin signaling (as well as others), are required for progenitor cell formation or activation and for cell proliferation and specification leading to tissue regrowth. Experimental activation of these pathways or interference with signals that inhibit regenerative processes can augment or even trigger regeneration in certain contexts.
Crystal structure of the human GINS complex
Authors: Choi Jung Min , Lim Hye Seong , Kim Jeong Joo , Song Ok-Kyu , Cho Yunje
Published: June 2007

The GINS complex mediates the assembly of the MCM2–7 (minichromosome maintenance) complex with proteins in a replisome progression complex. The eukaryotic GINS complex is composed of Sld5, Psf1, Psf2, and Psf3, which must be assembled for cell proliferation. We determined the crystal structure of the human GINS complex: GINS forms an elliptical shape with a small central channel. The structures of Sld5 and Psf2 resemble those of Psf1 and Psf3, respectively. In addition, the N-terminal and C-terminal domains of Sld5/Psf1 are permuted in Psf2/Psf3, which suggests that the four proteins have evolved from a common ancestor. Using a structure-based mutational analysis, we identified the functionally critical surface regions of the GINS complex.
Staphylococcus aureus RNAIII coordinately represses the synthesis of virulence factors and the transcription regulator Rot by an antisense mechanism
Authors: Boisset Sandrine , Geissmann Thomas , Huntzinger Eric , Fechter Pierre , Bendridi Nadia , Possedko Maria , Chevalier Clément , Helfer Anne Catherine , Benito Yvonne , Jacquier Alain , Gaspin Christine , Vandenesch François , Romby Pascale
Published: June 2007

RNAIII is the intracellular effector of the quorum-sensing system in Staphylococcus aureus. It is one of the largest regulatory RNAs (514 nucleotides long) that are known to control the expression of a large number of virulence genes. Here, we show that the 3′ domain of RNAIII coordinately represses at the post-transcriptional level, the expression of mRNAs that encode a class of virulence factors that act early in the infection process. We demonstrate that the 3′ domain acts primarily as an antisense RNA and rapidly anneals to these mRNAs, forming long RNA duplexes. The interaction between RNAIII and the mRNAs results in repression of translation initiation and triggers endoribonuclease III hydrolysis. These processes are followed by rapid depletion of the mRNA pool. In addition, we show that RNAIII and its 3′ domain mediate translational repression of rot mRNA through a limited number of base pairings involving two loop–loop interactions. Since Rot is a transcriptional regulatory protein, we proposed that RNAIII indirectly acts on many downstream genes, resulting in the activation of the synthesis of several exoproteins. These data emphasize the multitude of regulatory steps affected by RNAIII and its 3′ domain in establishing a network of S. aureus virulence factors.
The RNA polymerase II CTD kinase Ctk1 functions in translation elongation
Authors: Röther Susanne , Sträßer Katja
Published: June 2007

Translation is a highly complex process that is regulated by a multitude of factors. Here, we show that the conserved kinase Ctk1 functions in translation by enhancing decoding fidelity. Ctk1 associates with translating ribosomes in vivo and is needed for efficient translation. Ctk1 phosphorylates Rps2, a protein of the small ribosomal subunit, on Ser 238. Importantly, Ctk1-depleted as well as rps2-S238A mutant cells show a defect in translation elongation through an increase in the frequency of miscoding. The role of Ctk1 in translation may be conserved as the mammalian homolog of Ctk1, CDK9, also associates with polysomes. Since Ctk1 interacts with the TREX (transcription and mRNA export) complex, which couples transcription to mRNA export, Ctk1/CDK9 might bind to correctly processed mRNPs during transcription and accompany the mRNP to the ribosomes in the cytoplasm, where Ctk1 enhances efficient and accurate translation of the mRNA.
FLOWERING LOCUS T Protein May Act as the Long-Distance Florigenic Signal in the Cucurbits
Authors: Lin Ming-Kuem , Belanger Helene , Lee Young-Jin , Varkonyi-Gasic Erika , Taoka Ken-Ichiro , Miura Eriko , Xoconostle-Cázares Beatriz , Gendler Karla , Jorgensen Richard A. , Phinney Brett , Lough Tony J. , Lucas William J.
Published: June 2007

Cucurbita moschata, a cucurbit species responsive to inductive short-day (SD) photoperiods, and Zucchini yellow mosaic virus (ZYMV) were used to test whether long-distance movement of FLOWERING LOCUS T (FT) mRNA or FT is required for floral induction. Ectopic expression of FT by ZYMV was highly effective in mediating floral induction of long-day (LD)–treated plants. Moreover, the infection zone of ZYMV was far removed from floral meristems, suggesting that FT transcripts do not function as the florigenic signal in this system. Heterografting demonstrated efficient transmission of a florigenic signal from flowering Cucurbita maxima stocks to LD-grown C. moschata scions. Real-time RT-PCR performed on phloem sap collected from C. maxima stocks detected no FT transcripts, whereas mass spectrometry of phloem sap proteins revealed the presence of Cm-FTL1 and Cm-FTL2. Importantly, studies on LD- and SD-treated C. moschata plants established that Cmo-FTL1 and Cmo-FTL2 are regulated by photoperiod at the level of movement into the phloem and not by transcription. Finally, mass spectrometry of florally induced heterografted C. moschata scions revealed that C. maxima FT, but not FT mRNA, crossed the graft union in the phloem translocation stream. Collectively, these studies are consistent with FT functioning as a component of the florigenic signaling system in the cucurbits.
Update on the Interaction of Rifampin and Warfarin
Authors: Kim Karissa Y. , Epplen Kelly , Foruhari Farzin , Alexandropoulos Hattie
Published: June 2007

A 79‐year‐old man with a history of deep vein thrombosis and pulmonary embolism received anticoagulation therapy with warfarin 5 mg daily for 8 months. He was diagnosed with osteomyelitis and underwent partial metatarsal resection of his right foot. After surgery, antibiotics were initiated, including ertapenem sodium 1 g intravenously every 24 hours, vancomycin 1400 mg intravenously every 24 hours, and rifampin 300 mg by mouth twice daily. Achieving a therapeutic level of anticoagulation was difficult despite escalating doses of warfarin, because of the interaction with rifampin. A 5‐ to 6‐fold increase in warfarin dose was prescribed to reach therapeutic international normalized ratios (INRs), but even these increases were insufficient to maintain his INR in the therapeutic range. After rifampin was discontinued, warfarin doses were gradually reduced over the next 2 months. When concurrent warfarin‐rifampin therapy is necessary, vigilant monitoring is imperative and significant increases in warfarin doses are likely.
Sleep Disturbances in Caregivers of Patients With End‐Stage Congestive Heart Failure: Part II—Assess and Intervene
Authors: Rausch Sarah M. , Baker Kathy , Boonmee Junyanee
Published: June 2007

Sleep disturbances in caregivers of patients with congestive heart failure is common. The consequences of sleep disturbances are dire and have potential to seriously impact caregiver health and patient outcomes. Therefore, it is imperative that the health care team, especially nurses, assess and intervene. Basic assessment of caregiver sleep disturbance can be quick and simple and can be performed while assessing the congestive heart failure patient's health. If a more complex sleep disorder is suspected, other assessments can be conducted if time and money permit. The benefits to properly assessing sleep disturbance and subsequent treatment far outweigh the minimal time spent by the health care team or caregiver.
Neuronal features of oligodendrogliomas—an ultrastructural and immunohistochemical study
Authors: Vyberg M , Ulhøi B P , Teglbjærg P S
Published: June 2007

Aims:  To assess neuronal differentiation in oligodendrogliomas (ODGs).

Methods and results:  An electron microscopic and immunohistochemical study of 41 consecutive cases was performed. In all cases, tumour cells with neuritic structures were identified ultrastructurally, including synapses and neurosecretory granules. For the immunohistochemical identification of synaptophysin, monoclonal antibody clones 27G12, Snp88 and SY38 and a polyclonal antibody were compared in optimized protocols on slides from a spectrum of tissues and 16 ODGs. 27G12 gave the best signal‐to‐noise ratio, while SY38 gave the poorest. When 27G12 was applied on all 41 ODGs, widespread immunoreactivity was obtained in 100%. Among three antibodies to chromogranin compared similarly, clone LK2H10 and a polyclonal antibody gave identical patterns of immunoreactivity, whereas clone DAK‐A3 gave weaker reactions. When LK2H10 was applied on all tumours, staining was found in 12 (29%). All tumours but one stained strongly for glial fibrillary acidic protein and all for synapsin I. Fluorescence in situ hybridization analysis showed a concomitant 1p/19q deletion in 12/16 ODGs.

Conclusions:  Our study provides evidence for widespread neuronal differentiation in ODGs, suggesting that these tumours may be derived from progenitor cells with limited commitment. Antibody selection and protocol optimization are mandatory for reliable immunohistochemistry results.
Nuclear survivin is associated with disease recurrence and poor survival in patients with cutaneous malignant melanoma
Authors: Piras F , Murtas D , Minerba L , Ugalde J , Floris C , Maxia C , Colombari R , Perra M T , Sirigu P
Published: June 2007

Aims:  Survivin is expressed in neoplastic cells and appears to be associated with resistance to therapy and shorter survival in various types of tumours. The aim of the present study was to determine whether nuclear or cytoplasmic expression of survivin is related to disease recurrence and overall survival of patients with Stage I and II melanoma according to the American Joint Committee on Cancer (AJCC) staging system.

Methods and results:  Immunohistochemistry was performed on formalin‐fixed paraffin‐embedded sections of primary cutaneous melanoma from 50 patients. Survival rates were estimated using the Kaplan–Meier method and compared using the log rank test. Association of clinical variables (gender, age, tumour location, thickness, Clark level and AJCC stage) with survivin expression was analysed by Fisher's exact test. Patients with nuclear immunoreactivity for survivin had an increased risk of disease recurrence during the first three postoperative years (P < 0.05) and of death (P < 0.05). Cytoplasmic immunoreactivity was not correlated with either survival or clinical variables.

Conclusions:  Nuclear presence of survivin may be an independent biomarker for disease recurrence and overall survival in patients with Stage I and II melanoma.
Expression of Bax, Bcl‐xL and Bcl‐2 proteins in relation to grade of inflammation and stage of fibrosis in chronic hepatitis C
Authors: Piekarska A , Kubiak R , Szymczak W , Piekarski J
Published: June 2007

Aims:  To determine the expression of regulators of apoptosis in chronic hepatitis C.

Methods and results:  Expression of Bax, Bcl‐xL and Bcl‐2 proteins was assessed immunohistochemically in liver biopsy specimens obtained from 89 adults with chronic hepatitis C. Expression of Bax in hepatocytes correlated inversely with grade of inflammation (P < 0.001) and stage of fibrosis (P = 0.011), classified according to the Scheuer score; expression of Bcl‐xL in hepatocytes did not correlate with grade of inflammation (P = 0.106) or stage of fibrosis (P = 0.078); maximum Bcl‐xL expression was observed in grade 3 inflammation and stage 4 fibrosis. Expression of Bcl‐2 protein in hepatocytes was present in only two cases (both with advanced disease); the expression of Bcl‐2 protein in interlobular bile duct epithelial cells correlated with the grade of inflammation (P = 0.018), but not with stage of fibrosis (P = 0.154). The expression of Bcl‐2 protein in lymphoid cells infiltrating portal zones and lobules did not correlate with grade of inflammation (P = 0.113) or stage of fibrosis (P = 0.815).

Conclusion:  Major differences in expression of studied proteins were observed in relation to grade of inflammation and stage of fibrosis in chronic hepatitis C.
Gastric mucin is expressed in a subset of endocervical tunnel clusters: type A tunnel clusters of gastric phenotype
Authors: Kondo T , Hashi A , Murata S‐I , Fischer S E , Nara M , Nakazawa T , Yuminamochi T , Hoshi K , Katoh R
Published: June 2007

Aims:  Gastric mucin expression has been demonstrated in a group of endocervical glandular lesions. The aim of this study was to gain further insight into endocervical lesions with a gastric phenotype.

Methods and results:  Various types of tunnel clusters (TC) were examined for gastric mucin by alcian blue/periodic acid–Schiff staining and immunohistochemistry for HIK1083. Five of 34 cases of TC expressed gastric mucin defined by PAS dominant neutral mucin and immunopositivity for pyloric gland mucin. Histologically, TC expressing gastric mucin showed lobular arrangements of small to medium‐sized glands composed of mucin‐rich columnar cells and were classified as Flumann's type A TC. Neither type B TC nor normal endocervical glands expressed PAS dominant neutral mucin and none of them was immunopositive for pyloric gland mucin. Five patients with type A TC of gastric phenotype ranged in age from 33 to 79 years (mean 58 years) and were multiparous. Type A TC of gastric phenotype, ranging from 2 to 4 mm in maximum diameter, were incidental findings in hysterectomy specimens.

Conclusion:  Type A TC of gastric phenotype could be related to lobular endocervical glandular hyperplasia of gastric phenotype. The pathogenesis of gastric metaplasia in TC remains unclear.
Grading of dysplasia in Barrett's oesophagus: substantial interobserver variation between general and gastrointestinal pathologists
Authors: Kerkhof M , Van Dekken H , Steyerberg E W , Meijer G A , Mulder A H , De Bruïne A , Driessen A , Ten Kate F J , Kusters J G , Kuipers E J , Siersema P D ,   for the CYBAR study group
Published: June 2007

Aims:  To determine interobserver variation in grading of dysplasia in Barrett's oesophagus (BO) between non‐expert general pathologists and expert gastrointestinal pathologists on the one hand and between expert pathologists on the other hand.

Methods and results:  In this prospective multicentre study, non‐expert and expert pathologists graded biopsy specimens of 920 patients with endoscopic BO, which were blindly reviewed by one member of a panel of expert pathologists (panel experts) and by a second panel expert in case of disagreement on dysplasia grade. Agreement between two of three pathologists was established as the final diagnosis. Analysis was performed by κ statistics. Due to absence of intestinal metaplasia, 127/920 (14%) patients were excluded. The interobserver agreement for dysplasia [no dysplasia (ND) versus indefinite for dysplasia/low‐grade dysplasia (IND/LGD) versus high‐grade dysplasia (HGD)/adenocarcinoma (AC)] between non‐experts and first panel experts and between initial experts and first panel experts was fair (κ = 0.24 and κ = 0.27, respectively), and substantial for differentiation of HGD/AC from ND/IND/LGD (κ = 0.62 and κ = 0.58, respectively).

Conclusions:  There was considerable interobserver variability in the interpretation of ND or IND/LGD in BO between non‐experts and experts, but also between expert pathologists. This suggests that less subjective markers are needed to determine the risk of developing AC in BO.
Haematopathology practice: the commonest problems encountered in a consultation practice
Authors: Isaacson P G
Published: June 2007

Although not specifically recognized as a subspecialty of histopathology, haematopathology has a long history of specialist practice in the UK, with a few centres attracting large numbers of referred cases. The specialist nature of haematopathology has been enhanced by the advent of immunohistochemistry and, more recently, molecular genetics, which now play a major role in the diagnosis of haematopoietic and lymphoid neoplasms. Problems encountered by non‐specialist pathologists, and reflected in those cases submitted for consultation, include difficulties in the differential diagnosis of certain benign lymphoproliferative disorders from lymphoma and the precise classification of lymphomas which may have an impact on therapeutic decisions. Lymphomas that frequently pose problems include common lesions such as follicular lymphoma and more esoteric disorders such as T‐cell/histiocyte‐rich large B‐cell lymphoma. This review is an attempt to clarify a logical approach to the differential diagnosis of these lesions.