bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of Individual Variation in Intracellular Accumulation of Anti-HIV Nucleoside Analog Metabolites
Authors: Paintsil Elijah , Dutschman Ginger E. , Hu Rong , Grill Susan P. , Wang Chuan-Jen , Lam Wing , Li Fang-Yong , Ghebremichael Musie , Northrup Veronika , Cheng Yung-Chi
Published: November 2010

Individual variation in response to antiretroviral therapy is well-known, but it is not clear if demographic characteristics such as gender, age, and ethnicity are responsible for the variation. To optimize anti-HIV therapy and guide antiretroviral drug discovery, determinants that cause variable responses to therapy need to be evaluated. We investigated the determinants of intracellular concentrations of nucleoside analogs using peripheral blood mononuclear cells from 40 healthy donors. We observed individual differences in the concentrations of the intracellular nucleoside analogs; the mean concentrations of the triphosphate metabolite of ethynylstavudine (4′-Ed4T), zidovudine (AZT), and lamivudine (3TC) were 0.71 pmol/106cells (minimum and maximum, 0.10 and 3.00 pmol/106cells, respectively), 0.88 pmol/106cells (minimum and maximum, 0.10 and 15.18 pmol/106cells, respectively), and 1.70 pmol/106cells (minimum and maximum, 0.20 and 7.73 pmol/106cells, respectively). Gender and ethnicity had no effect on the concentration of 4′-Ed4T and 3TC metabolites. There was a trend for moderation of the concentrations of AZT metabolites by gender (P= 0.17 for gender·metabolite concentration). We observed variability in the activity and expression of cellular kinases. There was no statistically significant correlation between thymidine kinase 1 (TK-1) activity or expression and thymidine analog metabolite concentrations. The correlation between the activity of deoxycytidine kinase (dCK) and the 3TC monophosphate metabolite concentration showed a trend toward significance (P= 0.1). We observed an inverse correlation between the multidrug-resistant protein 2 (MRP2) expression index and the concentrations of AZT monophosphate, AZT triphosphate, and total AZT metabolites. Our findings suggest that the observed variation in clinical response to nucleoside analogs may be due partly to the individual differences in the intracellular concentrations, which in turn may be affected by the cellular kinases involved in the phosphorylation pathway and ATP-binding cassette (ABC) transport proteins.
Granuloma Formation around Filarial Larvae Triggered by Host Responses to an Excretory/Secretory Antigen
Authors: Dash Yashodhara , Ramesh Manish , Kalyanasundaram Ramaswamy , Munirathinam Gnanasekar , Shultz Leonard D. , Rajan T. V.
Published: November 2010

In previous studies using a murine model of filarial infection, granuloma formation was found to be a most important host-protective mechanism. We have also shown thatin vitrocytoadherence is a surrogate for the formation of antifilarial granulomasin vivoand that it requires “alternatively activated” host cells and a source of antifilarial antibody. We show here that antibodies against L3 excretory/secretory (E/S) products can facilitatein vitrocytoadherence. We generated a set of hybridomas reactive with filarial E/S products and screened them for their ability to mediatein vitrocytoadherence. One clone (no. 1E9) was positive in this assay. We then screened a novel expression library of filarial antigens displayed on the surface of T7 bacteriophage for reactivity with 1E9. Phage expressing two filarial antigens (TCTP and BmALT-2) reacted with 1E9. Immunization of mice showed that the cohort immunized with BmALT-2 cleared a challenge infection with infectiveBrugia pahangiL3 in an accelerated manner, whereas cohorts immunized with TCTP cleared larvae with the same kinetics as in unimmunized mice. These data confirm that BmALT-2 is the antigenic target of granuloma-mediated killing ofB. pahangiL3. Our findings also confirm previous studies that BmALT-2 is a potential vaccine candidate for filarial infection. Our data reinforce the work of others and also provide a possible mechanism by which immune responses to BmALT-2 may provide host protection.
Host and Pathogen Glycosaminoglycan-Binding Proteins Modulate Antimicrobial Peptide Responses inDrosophila melanogaster
Authors: Wang Zhipeng , Flax Lindsay A. , Kemp Melissa M. , Linhardt Robert J. , Baron Miriam J.
Published: November 2010

During group B streptococcal infection, the alpha C protein (ACP) on the bacterial surface binds to host cell surface heparan sulfate proteoglycans (HSPGs) and facilitates entry of bacteria into human epithelial cells. Previous studies in aDrosophila melanogastermodel showed that binding of ACP to the sulfated polysaccharide chains (glycosaminoglycans) of HSPGs promotes host death and is associated with higher bacterial burdens. We hypothesized that ACP-glycosaminoglycan binding might determine infection outcome by altering host responses to infection, such as expression of antimicrobial peptides. As glycosaminoglycans/HSPGs also interact with a number of endogenous secreted signaling molecules inDrosophila, we examined the effects of host and pathogen glycosaminoglycan/HSPG-binding structures in host survival of infection and antimicrobial peptide expression. Strikingly, host survival after infection with wild-type streptococci was enhanced among flies overexpressing the endogenous glycosaminoglycan/HSPG-binding morphogen Decapentaplegic—a transforming growth factor β-likeDrosophilahomolog of mammalian bone morphogenetic proteins—but not by flies overexpressing a mutant, non-glycosaminoglycan-binding Decapentaplegic, or the other endogenous glycosaminoglycan/HSPG-binding morphogens, Hedgehog and Wingless. While ACP-glycosaminoglycan binding was associated with enhanced transcription of peptidoglycan recognition proteins and antimicrobial peptides, Decapentaplegic overexpression suppressed transcription of these genes during streptococcal infection. Further, the glycosaminoglycan-binding domain of ACP competed with Decapentaplegic for binding to the soluble glycosaminoglycan heparin in anin vitroassay. These data suggest that, in addition to promoting bacterial entry into host cells, ACP competes with Decapentaplegic for binding to glycosaminoglycans/HSPGs during infection and that these bacterial and endogenous glycosaminoglycan-binding structures determine host survival and regulate antimicrobial peptide transcription.
Downregulation of GbpB, a Component of the VicRK Regulon, Affects Biofilm Formation and Cell Surface Characteristics of
Streptococcus mutans
Authors: Duque Cristiane , Stipp Rafael N. , Wang Bing , Smith Daniel J. , Höfling José F. , Kuramitsu Howard K. , Duncan Margaret J. , Mattos-Graner Renata O.
Published: November 2010

The virulence of the dental caries pathogen
Streptococcus mutans
relies in part on the sucrose-dependent synthesis of and interaction with glucan, a major component of the extracellular matrix of tooth biofilms. However, the mechanisms by which secreted and/or cell-associated glucan-binding proteins (Gbps) produced by
S. mutans
participate in biofilm growth remain to be elucidated. In this study, we further investigate GbpB, an essential immunodominant protein with similarity to murein hydrolases. A conditional knockdown mutant that expressed
gbpB
antisense RNA under the control of a tetracycline-inducible promoter was constructed in strain UA159 (UACA2) and used to investigate the effects of GbpB depletion on biofilm formation and cell surface-associated characteristics. Additionally, regulation of
g
bpB
by the two-component system VicRK was investigated, and phenotypic analysis of a
vicK
mutant (UA
vicK
) was performed. GbpB was directly regulated by VicR, and several phenotypic changes were comparable between UACA2 and UA
vicK
, although differences between these strains existed. It was established that GbpB depletion impaired initial phases of sucrose-dependent biofilm formation, while exogenous native GbpB partially restored the biofilm phenotype. Several cellular traits were significantly affected by GbpB depletion, including altered cell shape, decreased autolysis, increased cell hydrophobicity, and sensitivity to antibiotics and osmotic and oxidative stresses. These data provide the first experimental evidence for GbpB participation in sucrose-dependent biofilm formation and in cell surface properties.
Mycobacterium tuberculosis
Lipoproteins Directly Regulate Human Memory CD4
+
T Cell Activation via Toll-Like Receptors 1 and 2
Authors: Lancioni Christina L. , Li Qing , Thomas Jeremy J. , Ding XueDong , Thiel Bonnie , Drage Michael G. , Pecora Nicole D. , Ziady Assem G. , Shank Samuel , Harding Clifford V. , Boom W. Henry , Rojas Roxana E.
Published: November 2010

The success of
Mycobacterium tuberculosis
as a pathogen relies on its ability to regulate the host immune response.
M. tuberculosis
can manipulate adaptive T cell responses indirectly by modulating antigen-presenting cell (APC) function or by directly interacting with T cells. Little is known about the role of
M. tuberculosis
molecules in direct regulation of T cell function. Using a biochemical approach, we identified lipoproteins LprG and LpqH as major molecules in
M. tuberculosis
lysate responsible for costimulation of primary human CD4
+
T cells. In the absence of APCs, activation of memory CD4
+
T cells with LprG or LpqH in combination with anti-CD3 antibody induces Th1 cytokine secretion and cellular proliferation. Lipoprotein-induced T cell costimulation was inhibited by blocking antibodies to Toll-like receptor 2 (TLR2) and TLR1, indicating that human CD4
+
T cells can use TLR2/TLR1 heterodimers to directly respond to
M. tuberculosis
products.
M. tuberculosis
lipoproteins induced NF-κB activation in CD4
+
T cells in the absence of TCR co-engagement. Thus, TLR2/TLR1 engagement alone by
M. tuberculosis
lipoprotein triggered intracellular signaling, but upregulation of cytokine production and proliferation required co-engagement of the TCR. In conclusion, our results demonstrate that
M. tuberculosis
lipoproteins LprG and LpqH participate in the regulation of adaptive immunity not only by inducing cytokine secretion and costimulatory molecules in innate immune cells but also through directly regulating the activation of memory T lymphocytes.
Impact of Glutamine Transporters on Pneumococcal Fitness under Infection-Related Conditions
Authors: Härtel Tobias , Klein Matthias , Koedel Uwe , Rohde Manfred , Petruschka Lothar , Hammerschmidt Sven
Published: November 2010

The genomic analysis ofStreptococcuspneumoniaepredicted six putative glutamine uptake systems, which are expressed underinvitroconditions, as shown here by reverse transcription-PCR. Four of these operons consist ofglnHPQ, while two lackglnH, which encodes a soluble glutamine-binding protein. Here, we studied the impact of two of these glutamine ATP-binding cassette transporters onS.pneumoniaeD39 virulence and phagocytosis, which consist of GlnQ and a translationally fused protein of GlnH and GlnP. Mice infected intranasally with D39Δgln0411/0412showed significantly increased survival times and a significant delay in the development of pneumococcal pneumonia compared to those infected with D39, as observed in real time using bioluminescent pneumococci. In a mouse sepsis model, the mutant D39Δgln0411/0412showed only moderate but significant attenuation. In contrast, the D39Δgln1098/1099knockout strain was massively attenuated in the pneumonia and septicemia mouse infection model. To cause pneumonia or sepsis with D39Δgln1098/1099, infection doses 100- to 10,000-fold higher than those used for wild-type strain D39 were required. In an experimental mouse meningitis model, D39Δgln1098/1099produced decreased levels of white blood cells in cerebrospinal fluid and showed decreased numbers of bacteria in the bloodstream compared to D39 and D39Δgln0411/0412. Phagocytosis experiments revealed significantly decreased intracellular survival rates of mutants D39Δgln1098/1099and D39Δgln0411/0412compared to wild-type D39, suggesting that the deficiency of Gln uptake systems impairs resistance to oxidative stress. Taken together, our results demonstrate that both glutamine uptake systems are required for full virulence of pneumococci but exhibit different impacts on the pathogenesis of pneumococci underinvivoconditions.
Vaccination againstChlamydiaGenital Infection Utilizing the MurineC. muridarumModel
Authors: Farris Christina M. , Morrison Richard P.
Published: November 2010

Chlamydia trachomatisgenital infection is a worldwide public health problem, and considerable effort has been expended on developing an efficacious vaccine. The murine model ofC. muridarumgenital infection has been extremely useful for identification of protective immune responses and in vaccine development. Although a number of immunogenic antigens have been assessed for their ability to induce protection, the majority of studies have utilized the whole organism, the major outer membrane protein (MOMP), or the chlamydial protease-like activity factor (CPAF). These antigens, alone and in combination with a variety of immunostimulatory adjuvants, have induced various levels of protection against infectious challenge, ranging from minimal to nearly sterilizing immunity. Understanding of the mechanisms of natural infection-based immunity and advances in adjuvant biology have resulted in studies that are increasingly successful, but a vaccine licensed for use in humans has not yet been brought to fruition. Here we review immunity to chlamydial genital infection and vaccine development using theC. muridarummodel.
Uropathogenic
Escherichia coli
Induces Chronic Pelvic Pain
Authors: Rudick Charles N. , Berry Ruth E. , Johnson James R. , Johnston Brian , Klumpp David J. , Schaeffer Anthony J. , Thumbikat Praveen
Published: November 2010

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating syndrome of unknown etiology often postulated, but not proven, to be associated with microbial infection of the prostate gland. We hypothesized that infection of the prostate by clinically relevant uropathogenic
Escherichia coli
(UPEC) can initiate and establish chronic pain. We utilized an
E. coli
strain newly isolated from a patient with CP/CPPS (strain CP1) and examined its molecular pathogenesis in cell culture and in a murine model of bacterial prostatitis. We found that CP1 is an atypical isolate distinct from most UPEC in its phylotype and virulence factor profile. CP1 adhered to, invaded, and proliferated within prostate epithelia and colonized the prostate and bladder of NOD and C57BL/6J mice. Using behavioral measures of pelvic pain, we showed that CP1 induced and sustained chronic pelvic pain in NOD mice, an attribute not exhibited by a clinical cystitis strain. Furthermore, pain was observed to persist even after bacterial clearance from genitourinary tissues. CP1 induced pelvic pain behavior exclusively in NOD mice and not in C57BL/6J mice, despite comparable levels of colonization and inflammation. Microbial infections can thus serve as initiating agents for chronic pelvic pain through mechanisms that are dependent on both the virulence of the bacterial strain and the genetic background of the host.
Human Leukocytes Kill
Aspergillus nidulans
by Reactive Oxygen Species-Independent Mechanisms
Authors: Henriet Stefanie S. V. , Hermans Peter W. M. , Verweij Paul E. , Simonetti Elles , Holland Steven M. , Sugui Janyce A. , Kwon-Chung Kyung J. , Warris Adilia
Published: November 2010

Invasive aspergillosis is a major threat for patients suffering from chronic granulomatous disease (CGD). Although
Aspergillus fumigatus
is the most commonly encountered
Aspergillus
species, the presence of
A. nidulans
appears to be disproportionately high in CGD patients. The purpose of this study was to investigate the involvement of the NADPH oxidase and the resulting reactive oxygen species (ROS) in host defense against fungi and to clarify their relationship toward
A. nidulans
. Murine CGD alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN) and peripheral blood mononuclear cells (PBMC) from healthy controls and CGD patients were challenged with either
A. fumigatus
or
A. nidulans
. Analysis of the antifungal effects of ROS revealed that
A. nidulans
, in contrast to
A. fumigatus
, is not susceptible to ROS. In addition, infection with live
A. nidulans
did not result in any measurable ROS release. Remarkably, human CGD PMN and PBMC and murine CGD AM were at least equipotent at arresting conidial germination compared to healthy controls. Blocking of the NADPH oxidase resulted in significantly reduced damage of
A. fumigatus
but did not affect
A. nidulans
hyphae. Furthermore, the microbicidal activity of CGD PMN was maintained toward
A. nidulans
but not
A. fumigatus
. In summary, antifungal resistance to
A. nidulans
is not directly ROS related. The etiology of
A. nidulans
infections in CGD cannot be explained by the simple absence of the direct microbicidal effect of ROS.
In vivo
, the NADPH oxidase is a critical regulator of innate immunity whose unraveling will improve our understanding of fungal pathogenesis in CGD.
A Comparative Genomic Analysis of Diverse Clonal Types of EnterotoxigenicEscherichia coliReveals Pathovar-Specific Conservation
Authors: Sahl Jason W. , Steinsland Hans , Redman Julia C. , Angiuoli Samuel V. , Nataro James P. , Sommerfelt Halvor , Rasko David A.
Published: November 2010

EnterotoxigenicEscherichia coli(ETEC) is a major cause of diarrheal illness in children less than 5 years of age in low- and middle-income nations, whereas it is an emerging enteric pathogen in industrialized nations. Despite being an important cause of diarrhea, little is known about the genomic composition of ETEC. To address this, we sequenced the genomes of five ETEC isolates obtained from children in Guinea-Bissau with diarrhea. These five isolates represent distinct and globally dominant ETEC clonal groups. Comparative genomic analyses utilizing a gene-independent whole-genome alignment method demonstrated that sequenced ETEC strains share approximately 2.7 million bases of genomic sequence. Phylogenetic analysis of this “core genome” confirmed the diverse history of the ETEC pathovar and provides a finer resolution of theE. colirelationships than multilocus sequence typing. No identified genomic regions were conserved exclusively in all ETEC genomes; however, we identified more genomic content conserved among ETEC genomes than among non-ETECE. coligenomes, suggesting that ETEC isolates share a genomic core. Comparisons of known virulence and of surface-exposed and colonization factor genes across all sequenced ETEC genomes not only identified variability but also indicated that some antigens are restricted to the ETEC pathovar. Overall, the generation of these five genome sequences, in addition to the two previously generated ETEC genomes, highlights the genomic diversity of ETEC. These studies increase our understanding of ETEC evolution, as well as provide insight into virulence factors and conserved proteins, which may be targets for vaccine development.
Coxiella burnetiiAcid Phosphatase Inhibits the Release of Reactive Oxygen Intermediates in Polymorphonuclear Leukocytes
Authors: Hill J. , Samuel J. E.
Published: November 2010

Coxiella burnetii, the etiological agent of Q fever, is a small, Gram-negative, obligate intracellular bacterium. Replication ofC. burnetiiduring infection has been shown to be increased by decreasing oxidative stress using p47phox −/−and iNOS−/−micein vivoand by pharmacologic inhibitorsin vitro. Building upon this model, we investigated the role polymorphonuclear leukocytes (PMN) play in the control of infection, since NADPH oxidase-mediated release of reactive oxygen intermediates (ROI) is a primary bactericidal mechanism for these cells that is critical for early innate clearance. Earlier studies suggested thatC. burnetiiactively inhibited release of ROI from PMN through expression of an unidentified acid phosphatase (ACP). Recent genomic annotations identified one open reading frame (CBU0335) which may encode a Sec- and type II-dependent secreted ACP. To test this model, viableC. burnetiipropagated in tissue culture host cells or axenic media,C. burnetiiextracts, or purified recombinant ACP (rACP) was combined with human PMN induced with 4-phorbol 12-myristate 13-acetate (PMA). The release of ROI was inhibited when PMN were challenged with viableC. burnetii,C. burnetiiextracts, or rACP but not when PMN were challenged with electron beam-inactivatedC. burnetii. C. burnetiiextracts and rACP were also able to inhibit PMA-induced formation of NADPH oxidase complex on PMN membranes, suggesting a molecular mechanism responsible for this inhibition. These data support a model in whichC. burnetiieludes the primary ROI killing mechanism of activated PMN by secreting at least one acid phosphatase.
ATTRACTORS FOR A LATTICE DYNAMICAL SYSTEM GENERATED BY NON-NEWTONIAN FLUIDS MODELING SUSPENSIONS
Authors: AMIGÓ JOSÉ M. , GIMÉNEZ ÁNGEL , MORILLAS FRANCISCO , VALERO JOSÉ
Published: November 2010

In this paper we consider a lattice dynamical system generated by a parabolic equation modeling suspension flows. We prove the existence of a global compact connected attractor for this system and the upper semicontinuity of this attractor with respect to finite-dimensional approximations. Also, we obtain a sequence of approximating discrete dynamical systems by the implementation of the implicit Euler method, proving the existence and the upper semicontinuous convergence of their global attractors.
GENERAL CYCLES OF POTENTIAL FORM
Authors: CARO A. , LINERO A.
Published: November 2010

We consider a general difference equation of order k of the form [Formula: see text] with f0 : (0, ∞) → (0, ∞), F : (0, ∞)k-1 → (0, ∞) continuous maps and initial conditions xi ∈ (0, ∞), i = 0, 1, …, k-1. Under the hypothesis that fx(y) := F(x, x, …, x)f0(y) is an involution, we provide all the (k + 1)-cycles of the above-mentioned type, and we prove that if F separates variables, then all the (k + 2)-cycles have a potential form [Formula: see text] where c > 0, αi ∈ ℝ, xi ∈ (0, ∞), i = 0, 1, …, k-1. For this reason, we also describe all the p-cycles of order k ≥ 2 having the above potential form. Moreover, taking the particular case k = 3 and p = 8 disproves Conjecture 2.1 from [Grove & Ladas, 2005].
TOPOLOGY AND PERIODIC ORBITS OF RING-SHAPED POTENTIALS AS A GENERALIZED 4-D ISOTROPIC OSCILLATOR
Authors: BALSAS M. C. , FERRER S. , JIMÉNEZ E. S. , VERA J. A.
Published: November 2010

In this work we study a generalized integrable biparametric family of 4-D isotropic oscillators. This family allows to treat, in a unified way, oscillators defined by the potentials given by Hartmann and Quesne and other ring-shaped systems. Using the Liouville–Arnold theorem and the analysis of the momentum map in its critical points, we obtain a complete topological classification of the different invariant sets of the phase flow of this problem. By this topological study and the calculation of the action-angle variables we obtain the full classification of periodic and quasiperiodic orbits for this system.
INFINITE RESONANT SOLUTIONS AND TURNING POINTS IN A PROBLEM WITH UNBOUNDED BIFURCATION
Authors: ARRIETA J. M. , PARDO R. , RODRÍGUEZ-BERNAL A.
Published: November 2010

We consider an elliptic equation -Δu + u = 0 with nonlinear boundary conditions ∂u/∂n = λu + g(λ, x, u), where (g(λ, x, s))/s → 0, as |s| → ∞. In [Arrieta et al., 2007, 2009] the authors proved the existence of unbounded branches of solutions near a Steklov eigenvalue of odd multiplicity and, among other things, provided tools to decide whether the branch is subcritical or supercritical. In this work, we give conditions on the nonlinearity, guaranteeing the existence of a bifurcating branch which is neither subcritical nor supercritical, having an infinite number of turning points and an infinite number of resonant solutions.
Advances in Quaternary studies in Tasmania
Authors: Colhoun Eric A. , Kiernan Kevin , Barrows Timothy T. , Goede Albert
Published: November 2010

The last 35 years have seen rapid advances in our knowledge of climate change during the Quaternary Period in Tasmania. Extensive mapping and new dating studies, particularly since the advent of exposure dating, have revealed that maximum ice advance occurred 1 Ma ago and later advances were less extensive. Ice advances occurred several times during the last 100 ka, not only during the Last Glacial Maximum. Deglaciation was rapid after 18 ka and complete by 14 ka. Ice strongly affected limestone and produced extensive glaciokarst with deranged surface drainage. Glacial sediment plugged conduits to underground passages partially filled with glaciofluvial gravels. Periglacial erosion, and human impact since late oxygen isotope stage (OIS) 3, enhanced sediment influxes. New pollen records, particularly from Lake Selina, provide a 125 ka vegetation and climate record representative of the Southern Hemisphere. Finally, stable isotope studies of speleothem growth have revealed wide swings in climate. The climate was warm and moist during OIS 5e and early in OIS 1. Climate was cold and dry during OIS 5d and 4, and prevented speleothem growth during OIS 3 and OIS 2.
‘Of droughts and flooding rains’: an alluvial loess record from central South Australia spanning the last glacial cycle
Authors: Haberlah David , Glasby Peter , Williams Martin A. J. , Hill Steven M. , Williams Frances , Rhodes Edward J. , Gostin Victor , O'Flaherty Anthony , Jacobsen Geraldine E.
Published: November 2010

Deposits of proximal dust-derived alluvium (alluvial loess) within the catchments of the now semi-arid Flinders Ranges in South Australia record regionally synchronous intervals of fluvial entrainment, aggradation and down-cutting spanning the last glacial cycle. Today, these floodplain remnants are deeply entrenched and laterally eroded by ephemeral traction load streams. The north–south aligned ranges are strategically situated within the present-day transitional zone, receiving both topographically enhanced winter rainfall from the SW and convectional downpours from summer monsoonal incursions from the north. We develop a regional chronostratigraphy of depositional and erosional events emphasizing the Last Glacial Maximum (LGM). Based on 124 ages (94 accelerator mass spectrometry radiocarbon and 30 optically stimulated luminescence) from the most significant terrace remnants on both sides of the Ranges, we conclude that the last glacial cycle including the LGM was characterized by major environmental changes. Two pronounced periods of pedogenesis between
c
. 36 and 30 ka were followed by widespread erosion and reworking. A short-lived interval of climatic stability before
c
. 24 ka was followed by conditions in which large amounts of proximal dust (loess) were deposited across the catchments. These loess mantles were rapidly redistributed and episodically transported downstream by floods. The termination of this regime
c
. 18–16 ka was marked by rapid incision.
Tectonic geomorphology of Australia
Authors: Quigley Mark C. , Clark Dan , Sandiford Mike
Published: November 2010

The Australian continent is actively deforming in response to far-field stresses generated by plate boundary interactions and buoyancy forces associated with mantle dynamics. On the largest scale (several 10
3
km), the submergence of the northern continental shelf is driven by dynamic topography caused by mantle downwelling along the Indo-Pacific subduction system and accentuated by a regionally elevated geoid. The emergence of the southern shelf is attributed to the progressive movement of Australia away from a dynamic topography low. On the intermediate scale (several 10
2
km), low-amplitude (
c
. 100–200 m) long-wavelength (
c
. 100–300 km) topographic undulations are driven by (1) anomalous, smaller-scale upper mantle convection, and/or (2) lithospheric-scale buckling associated with plate boundary tectonic forcing. On the smallest scale (10
1
km), fault-related deformation driven by partitioning of far-field stresses has modified surface topography at rates of up to
c
. 170 m Ma
−1
, generated more than 30–50% of the contemporary topographic relief between some of Australia's highlands and adjacent piedmonts, and exerted a first-order control on long-term (10
4
–10
6
a) bedrock erosion. Although Australia is often regarded as tectonically and geomorphologically quiescent, Neogene to Recent tectonically induced landscape evolution has occurred across the continent, with geomorphological expressions ranging from mild to dramatic.
Lithology and the evolution of bedrock rivers in post-orogenic settings: constraints from the high-elevation passive continental margin of SE Australia
Authors: Bishop Paul , Goldrick Geoff
Published: November 2010

Understanding the role of lithological variation in the evolution of topography remains a fundamental issue, especially in the neglected post-orogenic terrains. Such settings represent the major part of the Earth's surface and recent modelling suggests that a range of interactions can account for the presence of residual topography for hundreds of millions of years, thereby explaining the great antiquity of landscapes in such settings. Field data from the inland flank of the SE Australian high-elevation continental margin suggest that resistant lithologies act to retard or even preclude the headward transmission of base-level fall driven by the isostatic response to regional denudation. Rejuvenation, be it episodic or continuous, is ‘caught up’ on these resistant lithologies, meaning in effect that the bedrock channels and hillslopes upstream of these ‘stalled’ knickpoints have become detached from the base-level changes downstream of the knickpoints. Until these knickpoints are breached, therefore, catchment relief must increase over time, a landscape evolution scenario that has been most notably suggested by Crickmay and Twidale. The role of resistant lithologies indicates that detachment-limited conditions are a key to the longevity of some post-orogenic landscapes, whereas the general importance of transport-limited conditions in the evolution of post-orogenic landscapes remains to be evaluated in field settings. Non-steady-state landscapes may lie at the heart of widespread, slowly evolving post-orogenic settings, such as high-elevation passive continental margins, meaning that non-steady-state landscapes, with increasing relief through time, are the ‘rule’ rather than the exception.
Rethinking eastern Australian caves
Authors: Osborne R. A. L.
Published: November 2010

There are some 300 bodies of cavernous limestone in eastern Australia, extending from Precipitous Bluff in southeastern Tasmania to the Mitchell Palmer region in north Queensland. These impounded karsts, developed in Palaeozoic limestones of the Tasman Fold Belt System, contain many caves. The caves have a suite of features in common that allows them to be thought of as a major group: the Tasmanic Caves. The Tasmanic Caves include multiphase hypogene caves such as Cathedral Cave at Wellington and multiphase, multiprocess caves such as Jenolan with Carboniferous hypogene and younger paragenetic and fluvial elements. Active hypogene caves occur at Wee Jasper and possibly at five other localities. The Tasmanic Caves are one of the most complex suites of caves in folded Palaeozoic limestones in the world. Field techniques developed to study these caves are now being applied to complex caves in central Europe: in the Czech Republic, Hungary, Poland, Slovakia and Slovenia.
Are the Murray Canyons offshore southern Australia still active for sediment transport?
Authors: Schmidt S. , De Deckker P. , Etcheber H. , Caradec S.
Published: November 2010

The Australian continental margin hosts numerous canyons. Some of the most spectacular canyons are located offshore Kangaroo Island, and these are linked to ancient courses of the River Murray, which would have flowed across the very wide Lacepede Shelf during periods of low sea level. During the AUSCAN-1 project, modern sedimentation was assessed using a multi-tracer approach on interface sediments from 350 to 2500 m water depth. The presence of freshly deposited particles, tagged by
234
Th in excess,
210
Pb-based sediment accumulation (0.03–0.13 cm a
−1
) and
230
Th-based focusing ratios, supports the occurrence of significant advection of marine sediments within these canyons. In the absence of direct riverine inputs, the shelf, being the site of intensive carbonate production, is the main supplier of material. The presence of incised channels in the eastern portion of the Murray Canyons Group (MCG) indicates recent to sub-recent activity along the canyons. The presence of underwater slides in the western side of the MCG confirms that sediment transport to the abyssal plain does occur. Based on our preliminary investigation and by synthesizing previous work on other canyons, we provide a conceptual model for sediment focusing and transfer within the canyons offshore Australia.
East Australian marine abrasion surface
Authors: Thom Bruce G. , Keene Jock B. , Cowell Peter J. , Daley Marc
Published: November 2010

Almost one-third of the seabed off the coastline north and south of Sydney comprises a planated bedrock surface, evident from sidescan surveys over the inner continental shelf. In seismic records, this rock surface extends up to 23 km offshore from the sea cliffs along 300 km of the coast. The rock surface dips offshore to as much as 180 m below sea level, where it merges with a major unconformity in the shelf sediment wedge. The surface is eroded into Mesozoic and Palaeozic rocks and is heavily dissected by sediment-filled, palaeo-valley incision and structural jointing. The sediment-fills comprise sand wedges that thicken landwards to form beaches and estuarine flood-tide deltas, respectively, in smaller and larger palaeo-valleys incised to below present sea level. At the base of the cliffs, the planated surface is buried by shelf sand bodies up to 30 m thick in places. The seaward edge of the surface is everywhere buried by the onlapping continental-shelf sediment wedge. The contiguity of the abrasion surface with the unconformity in the shelf sediment wedge suggests that marine planation began in the Mid-Oligocene, indicating time-average rates of gross cliff retreat at about 1 mm a
−1
.
Geoarchaeology in Australia: understanding human-environment interactions
Authors: Holdaway Simon J. , Fanning Patricia C.
Published: November 2010

This paper reviews the long history of interaction between scientists working in geomorphology, stratigraphy, sedimentology and chronology and those working in archaeology to understand past human–environment interactions in Australia. Despite this close collaboration, differentiating environmental impacts from the influence of human behaviour has proven difficult in research on key topics such as the causes of megafauna extinction, the significance of fire, and the impact of climatic shifts such as the El Niño–Southern Oscillation. Geoarchaeological research focused on depositional environments and post-depositional change in western New South Wales, Australia, provides important examples of how processes acting over different temporal scales affect archaeological deposits. The archaeological record is in some places discontinuous in time because geomorphological activity has removed the record of particular time periods, and it is discontinuous in space because it is preserved only in places that are geomorphologically relatively inactive. Important inferences concerning past human behaviours may be drawn from the record, but the processes responsible for both the presence and absence of the record must be considered. More attention needs to be given to ensuring that datasets with a similar temporal resolution are compared if the causes for behavioural changes in the past are to be correctly understood.
Ecogeomorphology in the Australian drylands and the role of biota in mediating the effects of climate change on landscape processes and evolution
Authors: Dunkerley David
Published: November 2010

Australian dryland landscape has developed under the influence of aridity, low relief, tectonic stability and biota adapted to nutrient and water scarcity. The biota in general, but notably the plants, mediates the impact of water scarcity and of climate change on ecohydrological and geomorphological processes. It reduce the partitioning of rain into overland flow, and so limit soil erosion, notably through the development of patch structures that partition the landscape into local runoff sources and runon sinks. In large rain events, when flow does reach ephemeral streams, channel-associated plants again modify flow conditions, reducing flow speeds and flow competence. Given the diverse influences of biota on landscape processes, it is argued that it likewise moderated the effects of Quaternary and Holocene climate change. Field evidence from Australian and other drylands suggests that the effect of changing land surface properties on runoff and erosion may exceed the effect of moderate climate change. Knowledge of the role of dryland biota and its role in land surface change is therefore a prerequisite to understanding the responses of landscapes to climate change, to understanding the complex spatio-temporal variability in landscape development, and to developing the ability to correctly interpret the alluvial record of changing geomorphological processes in terms of changes in climate and other external drivers.
History of Australian aridity: chronology in the evolution of arid landscapes
Authors: Fujioka Toshiyuki , Chappell John
Published: November 2010

Australian climate and vegetation, known from marine and lacustrine sediments and fossils, varied dramatically throughout the Cenozoic Era, with several warm reversals superimposed on overall drying and cooling. A suite of landforms, including stony deserts, dunefields and playa lakes, formed in response to the advancing aridity but their age generally remained uncertain until fairly recently, owing to a lack of suitable dating methods. Within the last 5 years, the chronology of Late Quaternary fluctuations of lakes, dunes and dust-mantles has been established by luminescence dating methods, and mid-Pleistocene onset of playa conditions in a few closed basins has been estimated using palaeomagnetic reversal chronology. Only recently has it been shown, by cosmogenic isotope dating, that major tracts of arid landforms including the Simpson Desert dunefield, and stony deserts of the Lake Eyre Basin, were formed in early Pleistocene and late Pliocene times, respectively. These landscapes represent a stepwise response to progressive climatic drying and, speculatively, were accompanied by biological adaptations. Recent molecular DNA studies indicate that Australia's arid-adapted species evolved from mesic-adapted ancestors during the Pliocene or earlier, but whether speciation rapidly accompanied the development of stony deserts and other arid geomorphological provinces awaits further studies of arid landscape chronology.
Characterization of Fixed and Reconfigurable Multi-Core Devices for Application Acceleration
Authors: Williams Jason , Massie Chris , George Alan D. , Richardson Justin , Gosrani Kunal , Lam Herman
Published: November 2010

As on-chip transistor counts increase, the computing landscape has shifted to multi- and many-core devices. Computational accelerators have adopted this trend by incorporating both fixed and reconfigurable many-core and multi-core devices. As more, disparate devices enter the market, there is an increasing need for concepts, terminology, and classification techniques to understand the device tradeoffs. Additionally, computational performance, memory performance, and power metrics are needed to objectively compare devices. These metrics will assist application scientists in selecting the appropriate device early in the development cycle. This article presents a hierarchical taxonomy of computing devices, concepts and terminology describing reconfigurability, and computational density and internal memory bandwidth metrics to compare devices.
Molecular Dynamics Simulations on High-Performance Reconfigurable Computing Systems
Authors: Chiu Matt , Herbordt Martin C.
Published: November 2010

The acceleration of molecular dynamics (MD) simulations using high-performance reconfigurable computing (HPRC) has been much studied. Given the intense competition from multicore and GPUs, there is now a question whether MD on HPRC can be competitive. We concentrate here on the MD kernel computation: determining the short-range force between particle pairs. In one part of the study, we systematically explore the design space of the force pipeline with respect to arithmetic algorithm, arithmetic mode, precision, and various other optimizations. We examine simplifications and find that some have little effect on simulation quality. In the other part, we present the first FPGA study of the filtering of particle pairs with nearly zero mutual force, a standard optimization in MD codes. There are several innovations, including a novel partitioning of the particle space, and new methods for filtering and mapping work onto the pipelines. As a consequence, highly efficient filtering can be implemented with only a small fraction of the FPGA’s resources. Overall, we find that, for an Altera Stratix-III EP3ES260, 8 force pipelines running at nearly 200 MHz can fit on the FPGA, and that they can perform at 95% efficiency. This results in an 80-fold per core speed-up for the short-range force, which is likely to make FPGAs highly competitive for MD.
Placement and Floorplanning in Dynamically Reconfigurable FPGAs
Authors: Montone Alessio , Santambrogio Marco D. , Sciuto Donatella , Memik Seda Ogrenci
Published: November 2010

The aim of this article is to describe a complete partitioning and floorplanning algorithm tailored for reconfigurable architectures deployable on FPGAs and considering communication infrastructure feasibility. This article proposes a novel approach for resource- and reconfiguration- aware floorplanning. Different from existing approaches, our floorplanning algorithm takes specific physical constraints such as resource distribution and the granularity of reconfiguration possible for a given FPGA device into account. Due to the introduction of constraints typical of other problems like partitioning and placement, the proposed approach is named floorplacer in order to underline the great differences with respect to traditional floorplanners. These physical constraints are typically considered at the later placement stage. Different aspects of the problems have been described, focusing particularly on the FPGAs resource heterogeneity and the temporal dimension typical of reconfigurable systems. Once the problem is introduced a comparison among related works has been provided and their limits have been pointed out. Experimental results proved the validity of the proposed approach.
A Simulation Framework for Rapid Analysis of Reconfigurable Computing Systems
Authors: Reardon Casey , Grobelny Eric , George Alan D. , Wang Gongyu
Published: November 2010

Reconfigurable computing (RC) is rapidly emerging as a promising technology for the future of high-performance and embedded computing, enabling systems with the computational density and power of custom-logic hardware and the versatility of software-driven hardware in an optimal mix. Novel methods for rapid virtual prototyping, performance prediction, and evaluation are of critical importance in the engineering of complex reconfigurable systems and applications. These techniques can yield insightful tradeoff analyses while saving valuable time and resources for researchers and engineers alike. The research described herein provides a methodology for mapping arbitrary applications to targeted reconfigurable platforms in a simulation environment called RCSE. By splitting the process into two domains, the application and simulation domains, characterization of each element can occur independently and in parallel, leading to fast and accurate performance prediction results for large and complex systems. This article presents the design of a novel framework for system-level simulative performance prediction of RC systems and applications. The article also presents a set of case studies analyzing two applications, Hyperspectral Imaging (HSI) and Molecular Dynamics (MD), across three disparate RC platforms within the simulation framework. The validation results using each of these applications and systems show that our framework can quickly obtain performance prediction results with reasonable accuracy on a variety of platforms. Finally, a set of simulative case studies are presented to illustrate the various capabilities of the framework to quickly obtain a wide range of performance prediction results and power consumption estimates.
High-Performance Quasi-Monte Carlo Financial Simulation
Authors: Tian Xiang , Benkrid Khaled
Published: November 2010

Quasi-Monte Carlo simulation is a special Monte Carlo simulation method that uses quasi-random or low-discrepancy numbers as random sample sets. In many applications, this method has proved advantageous compared to the traditional Monte Carlo simulation method, which uses pseudo-random numbers, thanks to its faster convergence and higher level of accuracy. This article presents the design and implementation of a massively parallelized Quasi-Monte Carlo simulation engine on an FPGA-based supercomputer, called Maxwell. It also compares this implementation with equivalent graphics processing units (GPUs) and general purpose processors (GPP)-based implementations. The detailed comparison between these three implementations (FPGA vs. GPP vs. GPU) is done in the context of financial derivatives pricing based on our Quasi-Monte Carlo simulation engine. Real hardware implementations on the Maxwell machine show that FPGAs outperform equivalent GPP-based software implementations by 2 orders of magnitude, with the speed-up figure scaling linearly with the number of processing nodes used (FPGAs/GPPs). The same implementations show that FPGAs achieve a ~ 3x speedup compared to equivalent GPU-based implementations. Power consumption measurements also show FPGAs to be 336x more energy efficient than CPUs, and 16x more energy efficient than GPUs.
Relaxin counteracts the altered gastric motility of dystrophic (mdx) mice: functional and immunohistochemical evidence for the involvement of nitric oxide
Authors: Vannucchi M. G. , Garella R. , Cipriani G. , Baccari M. C.
Published: November 2010

Impaired gastric motility ascribable to a defective nitric oxide (NO) production has been reported in dystrophic (mdx) mice. Since relaxin upregulates NO biosynthesis, its effects on the motor responses and NO synthase (NOS) expression in the gastric fundus of mdx mice were investigated. Mechanical responses of gastric strips were recorded via force displacement transducers. Evaluation of the three NOS isoforms was performed by immunohistochemistry and Western blot. Wild-type (WT) and mdx mice were distributed into three groups: untreated, relaxin pretreated, and vehicle pretreated. In strips from both untreated and vehicle-pretreated animals, electrical field stimulation (EFS) elicited contractile responses that were greater in mdx than in WT mice. In carbachol-precontracted strips, EFS induced fast relaxant responses that had a lower amplitude in mdx than in WT mice. Only in the mdx mice did relaxin depress the amplitude of the neurally induced excitatory responses and increase that of the inhibitory ones. In the presence of l-NNA, relaxin was ineffective. In relaxin-pretreated mdx mice, the amplitude of the EFS-induced contractile responses was decreased and that of the fast relaxant ones was increased compared with untreated mdx animals. Responses to methacholine or papaverine did not differ among preparations and were not influenced by relaxin. Immunohistochemistry and Western blotting showed a significant decrease in neuronal NOS expression and content in mdx compared with WT mice, which was recovered in the relaxin-pretreated mdx mice. The results suggest that relaxin is able to counteract the altered contractile and relaxant responses in the gastric fundus of mdx mice by upregulating nNOS expression.