bluuebunny/crossref_metadata_2025 huggingface dataset:
Granular hydrodynamics and pattern formation in vertically oscillated granular disk layers
Authors: CARRILLO JOSÉ A. , PÖSCHEL THORSTEN , SALUEÑA CLARA
Published: February 2008

The goal of this study is to demonstrate numerically that certain hydrodynamic systems, derived from inelastic kinetic theory, give fairly good descriptions of rapid granular flows even if they are way beyond their supposed validity limits. A numerical hydrodynamic solver is presented for a vibrated granular bed in two dimensions. It is based on a highly accurate shock capturing state-of-the-art numerical scheme applied to a compressible Navier–Stokes system for granular flow. The hydrodynamic simulation of granular flows is challenging, particularly in systems where dilute and dense regions occur at the same time and interact with each other. As a benchmark experiment, we investigate the formation of Faraday waves in a two-dimensional thin layer exposed to vertical vibration in the presence of gravity. The results of the hydrodynamic simulations are compared with those of event-driven molecular dynamics and the overall quantitative agreement is good at the level of the formation and structure of periodic patterns. The accurate numerical scheme for the hydrodynamic description improves the reproduction of the primary onset of patterns compared to previous literature. To our knowledge, these are the first hydrodynamic results for Faraday waves in two-dimensional granular beds that accurately predict the wavelengths of the two-dimensional standing waves as a function of the perturbation's amplitude. Movies are available with the online version of the paper.
Shaping Taxation: Economic Elites and Fiscal Decision-Making in Argentina, 1920–1945
Authors: ROMÁN JOSÉ ANTONIO SÁNCHEZ
Published: February 2008

This article deals with the process of decision-making in the sphere of taxation in Argentina between 1920 and 1945, focusing on the possible influence of the economic elites in that process. Given the central role of decisions over taxation in any fiscal policy and the momentous transformations that occurred in the Argentine system during this period, analysis of this subject can provide a better understanding of the political role that economic elites in Argentina played between the first presidency of Hipólito Yrigoyen (1916–22) and the ascent of Juan Domingo Perón to the presidency in 1946. Drawing on three key episodes in Argentina policy-making – the attempt to introduce an income tax in 1923, the response to the Depression in 1931–32, and the crisis of 1942–43, this article suggests that parliamentary institutions had stronger resilience in Argentina than is usually believed, and corporatist arrangements became rooted in Argentina only with difficulties.
Metamelanea umbonata new to the British Isles
Authors: Schultz Matthias
Published: February 2008

During a visit to the Natural History Museum London I examined material of the genus Porocyphus from the British Isles. A collection labelled Porocyphus coccodes [Scotland, Forfar, Caenlochan, on damp, E-facing rock (±basic), 1700 ft, 10 viii 1968, P. James (BM)] turned out to be a well-developed specimen of Metamelanea umbonata Henssen. Another two specimens from Scotland sent to me for identification belong here as well: Mid-Perth, Bread-albana, Creag Mhòr, S-facing cliffs, 700–800 m, 27/39.35, 6 vii 1979, B. Coppins 4573 (E, hb M. Schultz); Angus, Caenlochan Glen (N side), Glasallt Burn, W-facing cliffs, on vertical flushed granite cliff face, 800 m, 37/17, 7 viii 1989, B. Coppins 13383 & O. Gilbert (E, hb M. Schultz).
Studies on Eschatogonia (Ramalinaceae) in Peru
Authors: TIMDAL Einar
Published: February 2008

Four species of Eschatogonia are recognized in Peru: E. angustiloba Timdal sp. nov., E. dissecta Timdal & R. Sant. sp. nov., E. minuta Timdal & R. Sant. sp. nov., and E. prolifera (Mont.) R. Sant. African and South American material of E. prolifera are shown to belong in two different chemical strains. Eschatogonia prolifera is new to Guinea, Peru and Suriname. A key to all six known species of the genus is given.
Constraints on mantle source and interactions from He‐Sr isotope variation in Italian Plio‐Quaternary volcanism
Authors: Martelli M. , Nuccio P. M. , Stuart F. M. , Di Liberto V. , Ellam R. M.
Published: February 2008

Helium isotope ratios of olivine and pyroxene phenocrysts from Plio‐Quaternary volcanic rocks from southern Italy (seven Aeolian Islands, Mt. Vulture, Etna, Ustica, and Pantelleria) range from 2.3 to 7.1 Ra. Importantly, the phenocryst 3He/4He correlate well with whole rock Sr isotopic composition (0.70309–0.70711), reflecting the mixing of two sources. A significant contribution of He from crustal contamination is recorded only occasionally (e.g., pyroxenes from Vulcano). When merged with data from the Roman Comagmatic Province, a remarkably strong near‐linear He‐Sr isotope correlation is apparent. The general northward decrease in 3He/4He corresponds to an increase in 87Sr/86Sr (and a decrease in 143Nd/144Nd and 206Pb/204Pb) that is due to increasing metasomatic enrichment of the mantle wedge via subduction of the Ionian‐Adriatic plate. Calculations based on the ingrowth of 4He in the wedge and on the 4He content of the subducting crust show that mechanisms of enrichment in radiogenic He are effective only if the wedge is strongly depleted in He relative to best estimates of the depleted mantle. This can be accommodated if the process of metasomatism by the subduction fluids depletes the mantle wedge. The 3He/4He of Pantelleria, Etna, Iblei, Ustica, Alicudi, and Filicudi basalts (7.0 ± 0.6 Ra) define the mantle composition least affected by subduction‐related metasomatism. Although these volcanoes are from a variety of tectonic regimes (subduction‐related, intraplate, rifting), their similarities suggest a common origin of geochemical features. Their characteristics are consistent with a HIMU‐type mantle that either is younger than the Cook‐Austral island end‐member or has a lower 238U/204Pb.
Global and temporal distribution of meteoric smoke: A two‐dimensional simulation study
Authors: Megner L. , Siskind D. E. , Rapp M. , Gumbel J.
Published: February 2008

Meteoric material entering Earth's atmosphere ablates in the mesosphere and is then expected to recondense into tiny so‐called “smoke particles.” These particles are thought to be of great importance for middle atmosphere phenomena like noctilucent clouds, polar mesospheric summer echoes, metal layers, and heterogeneous chemistry. Commonly used one‐dimensional (1‐D) meteoric smoke profiles refer to average global conditions and yield of the order of a thousand nanometer sized particles per cubic centimeter at the mesopause, independent of latitude and time of year. Using the first two‐dimensional model of both coagulation and transport of meteoric material we here show that such profiles are too simplistic, and that the distribution of smoke particles indeed is dependent on both latitude and season. The reason is that the atmospheric circulation, which cannot be properly handled by 1‐D models, efficiently transports the particles to the winter hemisphere and down into the polar vortex. Using the assumptions commonly used in 1‐D studies results in number densities of nanometer sized particles of around 4000 cm−3 at the winter pole, while very few particles remain at the Arctic summer mesopause. If smoke particles are the only nucleation kernel for ice in the mesosphere this would imply that there could only be of the order of 100 or less ice particles cm−3 at the Arctic summer mesopause. This is much less than the ice number densities expected for the formation of ice phenomena (noctilucent clouds and polar mesospheric summer echoes) that commonly occur in this region. However, we find that especially the uncertainty of the amount of material that is deposited in Earth's atmosphere imposes a large error bar on this number, which may allow for number densities up to 1000 cm−3 near the polar summer mesopause. This efficient transport of meteoric material to the winter hemisphere and down into the polar vortex results in higher concentrations of meteoric material in the Arctic winter stratosphere than previously thought. This is of potential importance for the formation of the so‐called stratospheric condensation nuclei layer and for stratospheric nucleation processes.
Beneficial role of allicin from garlic in cervical cancer
Authors: Ansari Irfan Ahmad , Islam Najmul
Published: February 2008

Introduction: Cervical cancer remains a global health concern for females. Thus, in order to control cervical cancer, attempts are being made by researchers globally to somehow induce programmed cell death in the said cancerous cells. Wide spectrums of molecules are being probed for its ability to induce apoptosis in cervical cancer cells. Focus has now shifted in exploring natural compounds having antioxidant and anti-inflammatory molecules that may induce apoptosis in cancerous cells. Thus, we have employed allicin from garlic- a natural antioxidant, to probe the above in the present study.

Objective:

To probe whether or not allicin from garlic, a natural antioxidant, induces apoptosis in monocytes from patients with cervical cancer.

Results:

Allicin (500 ng/ml) reduced cell viability to 27% after 24 hours of treatment. Moreover, allicin-induced apoptosis was ascertained by measuring the activity of caspase-3, caspase-8 and caspase-9-like proteases in allicin treated and untreated monocytes from cervical cancer patients. Monocyte co-cultured with allicin for 24 hrs exhibited higher activity of caspase-3 followed by caspase-8 and caspase-9 like proteases, thereby indicating that the activation of caspase-3 like proteases was associated with reduced cell survival and apoptotic death of allicin-treated cervical cancer monocytes. This was ascertained by pre-treatment of cancer cells with cell permeable inhibitor Z-VAD-FMK (caspase-3 inhibitor), Z-IETD-FMK (caspase-8 inhibitor) and Z-LEHD-FMK (caspase-9 inhibitor) followed by allicin for 24 hrs (p<0.001). In this case, the cell viability assay showed that the presence of Z-VAD-FMK inhibitor blocked the effect of allicin on the viability of cancer monocytes (p<0.001).

Conclusion:

Allicin from garlic may act as an adjunct in the chemotherapy of cervical cancer.
Selecting the size of helium nanodroplets using time-resolved probing of a pulsed helium droplet beam
Authors: Yang Shengfu , Ellis Andrew M.
Published: February 2008

We show that helium nanodroplets generated using a pulsed valve undergo velocity dispersion according to their size. This makes it possible to use temporal selection to probe nanodroplets of a particular size within the pulsed gas profile rather than changing the expansion conditions as is done when using continuous helium nanodroplet sources. The variation in mean droplet size achievable within a single gas pulse can extend over more than an order of magnitude.
Kinetic energy operators in linearized internal coordinates
Authors: Pesonen Janne
Published: February 2008

It is customary to describe molecular vibrations using as exact kinetic energy operators and as accurate potentials as possible. It has become a standard approach to express Hamiltonians in curvilinear internal displacement coordinates, because they offer a simple and physical picture of vibrational motions, including large amplitude changes in the shape. In the older normal mode model of molecular vibrations, the nuclei are thought to vibrate infinitesimally about the reference configuration, and the shape of the molecule is described using linearized approximations of the true geometrically defined internal displacement coordinates. It is natural to ask how the two approaches are related. In this work, I present a general yet practical way to obtain curvilinear displacement coordinates as closed function of their linearized counterparts, and vice versa. In contrast to the conventional power series approach, the body-frame dependency is explicitly taken into account, and the relations are valid for any value of the coordinates. The present approach also allows one to obtain easily exact kinetic energy operators in linearized shape coordinates.
A homemade high-resolution orthogonal-injection time-of-flight mass spectrometer with a heated capillary inlet
Authors: Guo Changjuan , Huang Zhengxu , Gao Wei , Nian Huiqing , Chen Huayong , Dong Junguo , Shen Guoying , Fu Jiamo , Zhou Zhen
Published: February 2008

We describe a homemade high-resolution orthogonal-injection time-of-flight (O-TOF) mass spectrometer combing a heated capillary inlet. The O-TOF uses a heated capillary tube combined with a radio-frequency only quadrupole (rf-only quadrupole) as an interface to help the ion transmission from the atmospheric pressure to the low-pressure regions. The principle, configuration of the O-TOF, and the performance of the instrument are introduced in this paper. With electrospray ion source, the performances of the mass resolution, the sensitivity, the mass range, and the mass accuracy are described. We also include our results obtained by coupling atmospheric pressure matrix-assisted laser deporption ionization with this instrument.
Stability of atoms and molecules in an ultrarelativistic Thomas-Fermi-Weizsäcker model
Authors: Benguria Rafael D. , Loss Michael , Siedentop Heinz
Published: February 2008

We consider the zero mass limit of a relativistic Thomas-Fermi-Weizsäcker model of atoms and molecules. We find bounds for the critical nuclear charges that ensure stability.
Quantum electronic transport through supported Si29H24 clusters on an ideal Si[111] surface
Authors: Baltazar Samuel E. , De Menech Mario , Saalmann Ulf , Romero Aldo H. , Garcia Martin E.
Published: February 2008

We report calculations of the current-voltage (I-V) characteristics and the differential conductance of a Si29H24 cluster supported on an ideal Si[111] surface. Firstly, the distance between cluster and surface was optimized using ab initio calculations. Then, the electron transport was calculated by means of an extended Hückel model combined with a self-consistent calculation of the nonequilibrium Green’s functions. We find that the bond formation between cluster and surface leads to changes in the density of states of the cluster. The peak associated with this bond is located inside the energy gap of Si[111] diminishing its effect on the I-V characteristics, which exhibits a diodelike behavior. Finally, we determine the conductance spectra and characterize the charge distribution of the states which mainly contribute to transport at different bias voltages.
The Link between Service Privatization and Price Distribution among Consumer Types: Municipal Water Services in the Spanish Region of Catalonia
Authors: Miralles Antonio
Published: February 2008

In the Spanish region of Catalonia the industrial sector sensibly lobbied for the privatization of municipality-produced water services in the period 1996–2002. This paper analyzes the extent to which this result is consequent with observed measures of cross-subsidies in favor of residential consumers. I run a treatment-effects regression on a sample of 133 municipalities in 2000 and 2001. Recent privatization has a positive effect on the weight that the local regulator attaches to industrial users' welfare when deciding water tariffs. I conclude that an increase of industrial customers' group size has a twofold effect on the cross-subsidy in favor of residential customers: a direct positive substitution effect and an indirect negative political support effect through lobbying for service privatization.
Comparing Local Government Systems across Countries: Conceptual and Methodological Challenges to Building a Field of Comparative Local Government Studies
Authors: Wolman Harold
Published: February 2008

Despite increasing research on comparative local government, the resulting literature remains disappointing in that it is difficult to generalize across the range of diffuse studies. The main problem is the lack of a common framework to conduct such research and into which results can be placed and built upon. Partly, this is a consequence of insufficient attention to the requirements of building a classification system that can serve as a framework. In the spirit of contributing to the conceptual and methodological development of the literature on comparative local government, I set forth criteria for a classification system, review and assess the literature with respect to these criteria, and suggest a possible approach for building an empirically based classification system for local government that can serve as a common framework.
The Governance of Sustainable Development: Taking Stock and Looking Forwards
Authors: Jordan Andrew
Published: February 2008

The number of books and papers bearing the terms ‘sustainable development’ and ‘governance’ in their titles has grown exponentially in the last decade or so. The main purpose of this paper is to explore what meanings have been attached to these two essentially contested terms and to assess the extent to which the material on them constitutes an important, coherent, and cumulative body of scholarship. The first half explores the existing literatures on the two terms, and draws out some of the main similarities and differences. Drawing on papers that have been published in this journal over the last decade or so, the second half focuses on the attempts that have been made to build empirical and/or theoretical bridges between the two terms. The concluding section identifies a number of key themes and explores future research needs in what is evidently a vibrant and highly policy-relevant area of environmental social science research.
Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development
Authors: Cavazzuti Antonio , Paglietti Giuseppe , Hunter William N. , Gamarro Francisco , Piras Sandra , Loriga Mario , Allecca Sergio , Corona Paola , McLuskey Karen , Tulloch Lindsay , Gibellini Federica , Ferrari Stefania , Costi Maria Paola
Published: February 2008

Pteridine reductase (PTR1) is essential for salvage of pterins by parasitic trypanosomatids and is a target for the development of improved therapies. To identify inhibitors of
Leishmania major
and
Trypanosoma cruzi
PTR1, we combined a rapid-screening strategy using a folate-based library with structure-based design. Assays were carried out against folate-dependent enzymes including PTR1, dihydrofolate reductase (DHFR), and thymidylate synthase. Affinity profiling determined selectivity and specificity of a series of quinoxaline and 2,4-diaminopteridine derivatives, and nine compounds showed greater activity against parasite enzymes compared with human enzymes. Compound 6a displayed a
K
i
of 100 nM toward
Lm
PTR1, and the crystal structure of the
Lm
PTR1:NADPH:6a ternary complex revealed a substrate-like binding mode distinct from that previously observed for similar compounds. A second round of design, synthesis, and assay produced a compound (6b) with a significantly improved
K
i
(37 nM) against
Lm
PTR1, and the structure of this complex was also determined. Biological evaluation of selected inhibitors was performed against the extracellular forms of
T. cruzi
and
L. major
, both wild-type and overexpressing PTR1 lines, as a model for PTR1-driven antifolate drug resistance and the intracellular form of
T. cruzi.
An additive profile was observed when PTR1 inhibitors were used in combination with known DHFR inhibitors, and a reduction in toxicity of treatment was observed with respect to administration of a DHFR inhibitor alone. The successful combination of antifolates targeting two enzymes indicates high potential for such an approach in the development of previously undescribed antiparasitic drugs.
Centromere anatomy in the multidrug-resistant pathogen
Enterococcus faecium
Authors: Derome Andrew , Hoischen Christian , Bussiek Malte , Grady Ruth , Adamczyk Malgorzata , Kęedzierska Barbara , Diekmann Stephan , Barillà Daniela , Hayes Finbarr
Published: February 2008

Multidrug-resistant variants of the opportunistic human pathogen Enterococcus have recently emerged as leading agents of nosocomial infection. The acquisition of plasmid-borne resistance genes is a driving force in antibiotic-resistance evolution in enterococci. The segregation locus of a high-level gentamicin-resistance plasmid, pGENT, in
Enterococcus faecium
was identified and dissected. This locus includes overlapping genes encoding PrgP, a member of the ParA superfamily of segregation proteins, and PrgO, a site-specific DNA binding homodimer that recognizes the
cenE
centromere upstream of
prgPO
. The centromere has a distinctive organization comprising three subsites, CESII separates CESI and CESIII, each of which harbors seven TATA boxes spaced by half-helical turns. PrgO independently binds both CESI and CESIII, but with different affinities. The topography of the complex was probed by atomic force microscopy, revealing discrete PrgO foci positioned asymmetrically at the CESI and CESIII subsites. Bending analysis demonstrated that
cenE
is intrinsically curved. The organization of the
cenE
site and of certain other plasmid centromeres mirrors that of yeast centromeres, which may reflect a common architectural requirement during assembly of the mitotic apparatus in yeast and bacteria. Moreover, segregation modules homologous to that of pGENT are widely disseminated on vancomycin and other resistance plasmids in enterococci. An improved understanding of segrosome assembly may highlight new interventions geared toward combating antibiotic resistance in these insidious pathogens.
Spatial mapping of the neurite and soma proteomes reveals a functional Cdc42/Rac regulatory network
Authors: Pertz Olivier C. , Wang Yingchun , Yang Feng , Wang Wei , Gay Laurie J. , Gristenko Marina A. , Clauss Therese R. , Anderson David J. , Liu Tao , Auberry Kenneth J. , Camp David G. , Smith Richard D. , Klemke Richard L.
Published: February 2008

Neurite extension and growth cone navigation are guided by extracellular cues that control cytoskeletal rearrangements. However, understanding the complex signaling mechanisms that mediate neuritogenesis has been limited by the inability to biochemically separate the neurite and soma for spatial proteomic and bioinformatic analyses. Here, we apply global proteome profiling in combination with a neurite purification methodology for comparative analysis of the soma and neurite proteomes of neuroblastoma cells. The spatial relationship of 4,855 proteins were mapped, revealing networks of signaling proteins that control integrins, the actin cytoskeleton, and axonal guidance in the extending neurite. Bioinformatics and functional analyses revealed a spatially compartmentalized Rac/Cdc42 signaling network that operates in conjunction with multiple guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) to control neurite formation. Interestingly, RNA interference experiments revealed that the different GEFs and GAPs regulate specialized functions during neurite formation, including neurite growth and retraction kinetics, cytoskeletal organization, and cell polarity. Our findings provide insight into the spatial organization of signaling networks that enable neuritogenesis and provide a comprehensive system-wide profile of proteins that mediate this process, including those that control Rac and Cdc42 signaling.
Dicer-dependent pathways regulate chondrocyte proliferation and differentiation
Authors: Kobayashi Tatsuya , Lu Jun , Cobb Bradley S. , Rodda Stephen J. , McMahon Andrew P. , Schipani Ernestina , Merkenschlager Matthias , Kronenberg Henry M.
Published: February 2008

Small noncoding RNAs, microRNAs (miRNAs), bind to messenger RNAs through base pairing to suppress gene expression. Despite accumulating evidence that miRNAs play critical roles in various biological processes across diverse organisms, their roles in mammalian skeletal development have not been demonstrated. Here, we show that Dicer, an essential component for biogenesis of miRNAs, is essential for normal skeletal development.
Dicer
-null growth plates show a progressive reduction in the proliferating pool of chondrocytes, leading to severe skeletal growth defects and premature death of mice. The reduction of proliferating chondrocytes in
Dicer
-null growth plates is caused by two distinct mechanisms: decreased chondrocyte proliferation and accelerated differentiation into postmitotic hypertrophic chondrocytes. These defects appear to be caused by mechanisms downstream or independent of the Ihh-PTHrP signaling pathway, a pivotal signaling system that regulates chondrocyte proliferation and differentiation. Microarray analysis of
Dicer
-null chondrocytes showed limited expression changes in miRNA-target genes, suggesting that, in the majority of cases, chondrocytic miRNAs do not directly regulate target RNA abundance. Our results demonstrate the critical role of the Dicer-dependent pathway in the regulation of chondrocyte proliferation and differentiation during skeletal development.
Robust but delayed thalamocortical activation of dendritic-targeting inhibitory interneurons
Authors: Tan Zhenjun , Hu Hang , Huang Z. Josh , Agmon Ariel
Published: February 2008

GABA-releasing cortical interneurons are crucial for the neural transformations underlying sensory perception, providing “feedforward” inhibition that constrains the temporal window for synaptic integration. To mediate feedforward inhibition, inhibitory interneurons need to fire in response to ascending thalamocortical inputs, and most previous studies concluded that ascending inputs activate mainly or solely proximally targeting, parvalbumin-containing “fast-spiking” interneurons. However, when thalamocortical axons fire at frequencies that are likely to occur during natural exploratory behavior, activation of fast-spiking interneurons is rapidly and strongly depressed, implying the paradoxical conclusion that feedforward inhibition is absent when it is most needed. To address this issue, we took advantage of lines of transgenic mice in which either parvalbumin- or somatostatin-containing interneurons express GFP and recorded the responses of interneurons from both subtypes to thalamocortical stimulation
in vitro
. We report that during thalamocortical activation at behaviorally expected frequencies, fast-spiking interneurons were indeed activated only transiently because of rapid depression of their thalamocortical inputs, but a subset of layer 5 somatostatin-containing interneurons were robustly and persistently activated after a delay, due to the facilitation and temporal summation of their thalamocortical excitatory postsynaptic potentials. Somatostatin-containing interneurons are considered distally targeting. Thus, they are likely to provide delayed dendritic inhibition during exploratory behavior, contributing to the maintenance of a balance between cortical excitation and inhibition while leaving a wide temporal window open for synaptic integration and plasticity in distal dendrites.
Discovery of CD8+T cell epitopes inChlamydia trachomatisinfection through use of caged class I MHC tetramers
Authors: Grotenbreg Gijsbert M. , Roan Nadia R. , Guillen Eduardo , Meijers Rob , Wang Jia-huai , Bell George W. , Starnbach Michael N. , Ploegh Hidde L.
Published: February 2008

Class I MHC tetramers allow direct phenotypic identification of CD8+T cell populations, but their production remains laborious. A peptide exchange strategy that employs class I MHC products loaded with conditional ligands (caged MHC molecules) provides a fast and straightforward method to obtain diverse arrays of class I MHC tetramers and facilitates CD8+T cell epitope discovery. Here, we describe the development of photocleavable analogs of the FAPGNYPAL (SV9) epitope that bind H-2Kband H-2Dbwith full retention of their structural and functional integrity. We ranked all possible H-2Kboctameric and H-2Dbnonameric epitopes that span the genome ofChlamydia trachomatisand prepared MHC tetramers from ≈2,000 of the highest scoring peptides by replacement of the SV9 analog with the peptide of choice. The resulting 2,000-member class I MHC tetramer array allowed the discovery of two variants of an epitope derived from polymorphic membrane protein I (PmpI) and an assessment of the kinetics of emergence and the effector function of the corresponding CD8+T cells.
Increased plant growth from nitrogen addition should conserve phosphorus in terrestrial ecosystems
Authors: Perring Michael P. , Hedin Lars O. , Levin Simon A. , McGroddy Megan , de Mazancourt Claire
Published: February 2008

Inputs of available nitrogen (N) to ecosystems have grown over the recent past. There is limited general understanding of how increased N inputs affect the cycling and retention of other potentially limiting nutrients. Using a plant–soil nutrient model, and by explicitly coupling N and phosphorus (P) in plant biomass, we examine the impact of increasing N supply on the ecosystem cycling and retention of P, assuming that the main impact of N is to increase plant growth. We find divergent responses in the P cycle depending on the specific pathway by which nutrients are lost from the ecosystem. Retention of P is promoted if the relative propensity for loss of plant available P is greater than that for the loss of less readily available organic P. This is the first theoretical demonstration that the coupled response of ecosystem-scale nutrient cycles critically depends on the form of nutrient loss. P retention might be lessened, or reversed, depending on the kinetics and size of a buffering reactive P pool. These properties determine the reactive pool's ability to supply available P. Parameterization of the model across a range of forest ecosystems spanning various environmental and climatic conditions indicates that enhanced plant growth due to increased N should trigger increased P conservation within ecosystems while leading to more dissolved organic P loss. We discuss how the magnitude and direction of the effect of N may also depend on other processes.
A causal role for ERG in neoplastic transformation of prostate epithelium
Authors: Klezovitch Olga , Risk Michael , Coleman Ilsa , Lucas Jared M. , Null Manda , True Lawrence D. , Nelson Peter S. , Vasioukhin Valeri
Published: February 2008

A significant proportion of human prostate cancers carry a chromosomal rearrangement resulting in the overexpression of the ETS transcription factor, ERG; however, the functional significance of this event is poorly understood. We report here that up-regulation of ERG transcript is sufficient for the initiation of prostate neoplasia. In agreement with measurements of ERG transcripts, we found that ERG protein is expressed in neoplastic human prostate epithelium. Overexpression of ERG in prostate cell lines increased cell invasion. Moreover, targeted expression of this transcript
in vivo
in luminal prostate epithelial cells of transgenic mice results in initiation of prostate neoplasia observed as the development of focal precancerous prostatic intraepithelial neoplasia (PIN). Similar to human cancers, luminal epithelial cells in these PIN lesions displace diminishing in numbers basal epithelial cells and establish direct contact with the stromal cell compartment. Loss of basal cells is considered to be one of the critical hallmarks of human prostate cancer; however, the mechanisms responsible for this event were unknown. We propose that up-regulation of ERG in human prostate cancer activates cell invasion programs that subsequently displace basal cells by neoplastic epithelium. Our data demonstrate that ERG plays an important causal role in the transformation of prostate epithelium and should be considered as a target for prevention or early therapeutic intervention.
Variability in Rates of Use of Antibacterials Among 130 US Hospitals and Risk-Adjustment Models for Interhospital Comparison
Authors: MacDougall Conan , Polk Ronald E.
Published: February 2008

Objective.

To describe variability in rates of antibacterial use in a large sample of US hospitals and to create risk-adjusted models for interhospital comparison.

Methods.

We retrospectively surveyed the use of 87 antibacterial agents on the basis of electronic claims data from 130 medical-surgical hospitals in the United States for the period August 2002 to July 2003; these records represented 1,798,084 adult inpatients. Hospitals were assigned randomly to the derivation data set (65 hospitals) or the validation data set (65 hospitals). Multivariable models predicting rates of antibacterial use were created using the derivation data set. These models were then used to predict rates of antibacterial use in the validation data set, which was compared with observed rates of antibacterial use. Rates of antibacterial use was measured in days of therapy per 1,000 patient-days.

Results.

Across the surveyed hospitals, a mean of 59.3% of patients received at least 1 dose of an antimicrobial agent during hospitalization (range for individual hospitals, 44.4%-73.6%). The mean total rate of antibacterial use was 789.8 days of therapy per 1,000 patient-days (range, 454.4-1,153.4). The best model for the total rate of antibacterial use explained 31% of the variance in rates of antibacterial use and included the number of hospital beds, the number of days in the intensive care unit per 1,000 patient-days, the number of surgeries per 1,000 discharges, and the number of cases of pneumonia, bacteremia, and urinary tract infection per 1,000 discharges. Five hospitals in the validation data set were identified as having outlier rates on the basis of observed antibacterial use greater than the upper bound of the 90% prediction interval for predicted antibacterial use in that hospital.

Conclusion.

Most adult inpatients receive antimicrobial agents during their hospitalization, but there is substantial variability between hospitals in the volume of antibacterials used. Risk-adjusted models can explain a significant proportion of this variation and allow for comparisons between hospitals for benchmarking purposes.
Assessment of Clostridium difficile–Associated Disease Surveillance Definitions, North Carolina, 2005
Authors: Kutty Preeta K. , Benoit Stephen R. , Woods Christopher W. , Sena Arlene C. , Naggie Susanna , Frederick Joyce , Engemann John , Evans Sharon , Pien Brian C. , Banerjee Shailendra N. , Engel Jeffery , McDonald L. Clifford
Published: February 2008

Objective.

To determine the timing of community-onset Clostridium difficile–associated disease (CDAD) relative to the patient's last healthcare facility discharge, the association of postdischarge cases with healthcare facility–onset cases, and the influence of postdischarge cases on overall rates and interhospital comparison of rates of CDAD.

Design.

Retrospective cohort study for the period January 1, 2005, through December 31, 2005.

Setting.

Catchment areas of 6 acute care hospitals in North Carolina.

Methods.

We reviewed medical and laboratory records to determine the date of symptom onset, the dates of hospitalization, and stool C. difficile toxin assay results for patients with CDAD who had diarrhea and positive toxin–assay results. Cases were classified as healthcare facility–onset if they were diagnosed more than 48 hours after admission. Cases were defined as community-onset if they were diagnosed in the community or within 48 hours after admission, and were also classified on the basis of the time since the last discharge: if within 4 weeks, community-onset, healthcare facility–associated (CO-HCFA); if 4-12 weeks, indeterminate exposure; and if more than 12 weeks, community-associated. Pearson's correlation coefficient was used to assess the association between monthly rates of healthcare facility–onset, healthcare facility–associated (HO-HCFA) cases and CO-HCFA cases. We performed interhospital rate comparisons using HO-HCFA cases only and using both HO-HCFA and CO-HCFA cases.

Results.

Of 1046 CDAD cases, 442 (42%) were HO-HCFA cases and 604 (58%) were community-onset cases. Of the 604 community-onset cases, 94 (15%) were CO-HCFA, 40 (7%) were of indeterminate exposure, and 208 (34%) community-associated. A modest correlation was found between monthly rates of HO-HCFA cases and CO-HCFA cases across the 6 hospitals (r = 0.63, P<.001). Interhospital rankings changed for 6 of 11 months if CO-HCFA cases were included.

Conclusions.

A substantial proportion of community-onset cases of CDAD occur less than 4 weeks after discharge from a healthcare facility, and inclusion of CO-HCFA cases influences interhospital comparisons. Our findings support the use of a proposed definition of healthcare facility–associated CDAD that includes cases that occur within 4 weeks after discharge.
Prediction of zinc-binding sites in proteins from sequence
Authors: Shu Nanjiang , Zhou Tuping , Hovmöller Sven
Published: February 2008

Motivation: Motivated by the abundance, importance and unique functionality of zinc, both biologically and physiologically, we have developed an improved method for the prediction of zinc-binding sites in proteins from their amino acid sequences.

Results: By combining support vector machine (SVM) and homology-based predictions, our method predicts zinc-binding Cys, His, Asp and Glu with 75% precision (86% for Cys and His only) at 50% recall according to a 5-fold cross-validation on a non-redundant set of protein chains from the Protein Data Bank (PDB) (2727 chains, 235 of which bind zinc). Consequently, our method predicts zinc-binding Cys and His with 10% higher precision at different recall levels compared to a recently published method when tested on the same dataset.

Availability: The program is available for download at www.fos.su.se/~nanjiang/zincpred/download/

Contact:  svenh@struc.su.se

Supplementary information: All Supplementary Data can be accessed at www.fos.su.se/~nanjiang/zincpred/suppliment
Model-based Bayesian clustering (MBBC)
Authors: Joo Yongsung , Booth James G. , Namkoong Younghwan , Casella George
Published: February 2008

Motivation: The program MBBC 2.0 clusters time–course microarray data using a Bayesian product partition model.

Results: The Bayesian product partition model in Booth et al. (2007) simultaneously searches for the optimal number of clusters, and assigns cluster memberships based on temporal changes of gene expressions. MBBC 2.0 to makes this method easily available for statisticians and scientists, and is built with three free computer language software packages: Ox, R and C++, taking advantage of the strengths of each language. Within MBBC, the search algorithm is implemented with Ox and resulting graphs are drawn with R. A user-friendly graphical interface is built with C++ to run the Ox and R programs internally. Thus, MBBC users are not required to know how to use Ox, R or C++, but they must be pre-installed.

Availability: A self-extractable zip file, MBBC20zip.exe, is available at the MBBC webpage www.stat.ufl.edu/~casella/mbbc/, which contains MBBC.exe, source files, and all other related files. The current version works only in the Windows operating system. A free installation program and overview for Ox is available at www.doornik.com. A detailed installation guide for Ox is provided by MBBC, and is accessible without installing Ox. R is available at www.r-project.org/.

Contact:  casella@stat.ufl.edu
De novo identification of highly diverged protein repeats by probabilistic consistency
Authors: Biegert A. , Söding J.
Published: February 2008

Motivation: An estimated 25% of all eukaryotic proteins contain repeats, which underlines the importance of duplication for evolving new protein functions. Internal repeats often correspond to structural or functional units in proteins. Methods capable of identifying diverged repeated segments or domains at the sequence level can therefore assist in predicting domain structures, inferring hypotheses about function and mechanism, and investigating the evolution of proteins from smaller fragments.

Results: We present HHrepID, a method for the de novo identification of repeats in protein sequences. It is able to detect the sequence signature of structural repeats in many proteins that have not yet been known to possess internal sequence symmetry, such as outer membrane β-barrels. HHrepID uses HMM–HMM comparison to exploit evolutionary information in the form of multiple sequence alignments of homologs. In contrast to a previous method, the new method (1) generates a multiple alignment of repeats; (2) utilizes the transitive nature of homology through a novel merging procedure with fully probabilistic treatment of alignments; (3) improves alignment quality through an algorithm that maximizes the expected accuracy; (4) is able to identify different kinds of repeats within complex architectures by a probabilistic domain boundary detection method and (5) improves sensitivity through a new approach to assess statistical significance.

Availability: Server: http://toolkit.tuebingen.mpg.de/hhrepid; Executables: ftp://ftp.tuebingen.mpg.de/pub/protevo/HHrepID

Contact:  soeding@lmb.uni-muenchen.de

Supplementary information: Supplementary data are available at Bioinformatics online.
Bayesian models based on test statistics for multiple hypothesis testing problems
Authors: Ji Yuan , Lu Yiling , Mills Gordon B.
Published: February 2008

Motivation: We propose a Bayesian method for the problem of multiple hypothesis testing that is routinely encountered in bioinformatics research, such as the differential gene expression analysis. Our algorithm is based on modeling the distributions of test statistics under both null and alternative hypotheses. We substantially reduce the complexity of the process of defining posterior model probabilities by modeling the test statistics directly instead of modeling the full data. Computationally, we apply a Bayesian FDR approach to control the number of rejections of null hypotheses. To check if our model assumptions for the test statistics are valid for various bioinformatics experiments, we also propose a simple graphical model-assessment tool.

Results: Using extensive simulations, we demonstrate the performance of our models and the utility of the model-assessment tool. In the end, we apply the proposed methodology to an siRNA screening and a gene expression experiment.

Contact:  yuanji@mdanderson.org

Supplementary information: Supplementary data are available at Bioinformatics online.
Seasonal Variation, Chemical Composition and Antioxidant Activity of Brazilian Propolis Samples
Authors: Teixeira Érica Weinstein , Message Dejair , Negri Giuseppina , Salatino Antonio , Stringheta Paulo César
Published: February 2008

Total phenolic contents, antioxidant activity and chemical composition of propolis samples from three localities of Minas Gerais state (southeast Brazil) were determined. Total phenolic contents were determined by the Folin–Ciocalteau method, antioxidant activity was evaluated by DPPH, using BHT as reference, and chemical composition was analyzed by GC/MS. Propolis from Itapecerica and Paula Cândido municipalities were found to have high phenolic contents and pronounced antioxidant activity. From these extracts, 40 substances were identified, among them were simple phenylpropanoids, prenylated phenylpropanoids, sesqui‐ and diterpenoids. Quantitatively, the main constituent of both samples was allyl‐3‐prenylcinnamic acid. A sample from Virginópolis municipality had no detectable phenolic substances and contained mainly triterpenoids, the main constituents being α‐ and β‐amyrins. Methanolic extracts from Itapecerica and Paula Cândido exhibited pronounced scavenging activity towards DPPH, indistinguishable from BHT activity. However, extracts from Virginópolis sample exhibited no antioxidant activity. Total phenolic substances, GC/MS analyses and antioxidant activity of samples from Itapecerica collected monthly over a period of 1 year revealed considerable variation. No correlation was observed between antioxidant activity and either total phenolic contents or contents of artepillin C and other phenolic substances, as assayed by CG/MS analysis.
Effects of climate and overfishing on zooplankton dynamics and ecosystem structure: regime shifts, trophic cascade, and feedback loops in a simple ecosystem
Authors: Möllmann Christian , Müller-Karulis Bärbel , Kornilovs Georgs , St John Michael A.
Published: February 2008

Möllmann, C., Müller-Karulis, B., Kornilovs, G., and St John, M. A. 2008. Effects of climate and overfishing on zooplankton dynamics and ecosystem structure: regime shifts, trophic cascade, and feeback loops in a simple ecosystem. – ICES Journal of Marine Science, 65: 302–310. The Central Baltic Sea is the largest brackish waterbody in the world ocean, containing a highly productive but low-diversity ecosystem. Climate-induced changes in hydrography recently caused an ecosystem regime shift with changes at all trophic levels. The most pronounced changes in the ecosystem occurred at the zooplankton and fish trophic levels. In the zooplankton, dominance changed between the copepods Pseudocalanus acuspes and Acartia spp., a result of reduced salinities and increased temperatures. The change in hydrography also affected the reproductive success of the major fish species, resulting in a change in dominance from the piscivorous cod (Gadus morhua) to the planktivorous sprat (Sprattus sprattus). First, we investigate statistically the occurrence of regime shifts in time-series of key hydrographic variables and the biomass time-series of key species. Second, we demonstrate a three-level trophic cascade involving zooplankton. Finally, we model the ecosystem effects of the abiotic and biotic changes on copepod biomass and recruitment of fish stocks. Our results demonstrate the linkage between climate-induced zooplankton and fish regime changes, and how overfishing amplified the climate-induced changes at both trophic levels. Hence, our study demonstrates (i) the multiple pathways along which climatic and anthropogenic pressures can propagate through the foodweb; (ii) how both effects act synergistically to cause and stabilize regime changes; and (iii) the crucial role of zooplankton in mediating these ecosystem changes.
An analysis of phase change material as thermal mass
Authors: Richardson M.J , Woods A.W
Published: February 2008

Temperature fluctuations within a building can be attenuated by thermal mass. Adding phase change material (PCM) to thermal mass increases the effective heat capacity during the phase transition. This can anchor the temperature of the mass in a narrow band around the melting point of the PCM, further reducing the temperature swings perceived by occupants of the room. A simple dimensionless model for thermal mass forced by a sinusoidally varying air temperature is developed to calculate the performance of the PCM. The mass temperature satisfies the heat equation, with a temperature-dependent thermal diffusivity, and is solved numerically.

For a given PCM, the energy stored and returned to the room, the surface temperature amplitude and the penetration depth of heat pulses into a hypothetical semi-infinite mass can all be calculated as a function of a single dimensionless parameter. For optimal performance, the latent heat of the PCM should be as large as possible, the melting temperature range should be narrow and the thickness of the mass should exceed the penetration depth. The PCM wallboard is shown to be potentially as effective as conventional concrete, so lightweight buildings could enjoy the benefits of thermal inertia commonly associated with heavyweight structures.