bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the in situ and MODIS albedo variability at multiple timescales in the Sahel
Authors: Samain O. , Kergoat L. , Hiernaux P. , Guichard F. , Mougin E. , Timouk F. , Lavenu F.
Published: July 2008

The variability of the Sahelian albedo is investigated through the combined analysis of 5 years of in situ radiation data from the African Monsoon Multidisciplinary Analysis northernmost sites and remotely sensed albedo from 7 years of Moderate Resolution Imaging Spectroradiometer data. Both data sets are found to be in good agreement in terms of correlation and bias. The drivers of albedo variability are identified by means of in situ measurements of biological and physical properties of the land surface collected over a network of 29 long‐term survey sites. Short‐term variability is dominated by changes in the spectral composition of incident radiation, which reflects aerosol optical depth and integrated water content, and changes in soil moisture, which have a short‐lived effect (1 d). Bush fires cause a marked decrease of albedo of the order of 10 d, whereas a dry season storm event is suspected to have increased albedo through litter and soil surface abrasion. Seasonal plant growth causes the largest changes in rainy season albedo, and displays a large interannual variability: Because of the 2004 drought, albedo increases steadily from late 2003 to early 2005 at latitude 15°N. Grazing pressure is found to impact albedo mostly in the dry season. Dry season albedo is controlled by the amount of litter and standing dead phytomass hiding the bright soils. Thus rainfall anomalies have a direct effect on albedo through plant growth but also a lagged effect caused by above normal amounts of dry phytomass that can persist until the arrival of the next monsoon. EOF analysis and Hovmüller diagrams show these effects to be present on a large scale.
Geostatistical interpolation using copulas
Authors: Bárdossy András , Li Jing
Published: July 2008

In many applications of geostatistical methods, the dependence structure of the investigated parameter is described solely with the variogram or covariance functions, which are susceptible to measurement anomalies and implies the assumption of Gaussian dependence. Moreover the kriging variance respects only observation density, data geometry and the variogram model. To address these problems, we borrow the idea from copulas, to depict the dependence structure without the influence of the marginal distribution. The methodology and basic hypotheses for application of copulas as geostatistical methods are discussed and the Gaussian copula as well as a non‐Gaussian copula are used in this paper. Copula parameters are estimated using a division of the observations into multipoint subsets and a subsequent maximization of the corresponding likelihood function. The interpolation is carried out with two different copulas, where the expected and median values are calculated from the copulas conditioned with the nearby observations. The full conditional copulas provide the estimation distributions for the unobserved locations and can be used to define confidence intervals which depend on both the observation geometry and values. Observations of a large scale groundwater quality measurement network in Baden‐Württemberg are used to demonstrate the methodology. Five groundwater quality parameters: chloride, nitrate, pH, sulfate and dissolved oxygen are investigated. All five parameters show non‐Gaussian dependence. The copula‐based interpolation results of the five parameters are compared to the results of conventional ordinary and indicator kriging. Different statistical measures including mean squared error, relative differences and probability scores are used to compare cross validation and split sampling results of the interpolation methods. The non‐Gaussian copulas give better results than the geostatistical interpolations. Validation of the confidence intervals shows that they are more realistic than the estimation variances obtained by ordinary kriging.
Application of the finite difference heterogeneous multiscale method to the Richards' equation
Authors: Chen Fulai , Ren Li
Published: July 2008

This paper extends the finite difference heterogeneous multiscale method (FDHMM) to simulate transient unsaturated water flow problems in random porous media. The numerical method is based on the use of two different schemes for the original equation, at different grid levels which allows numerical results at a lower cost than solving the original equations. The main feature of FDHMM is that the necessary data for the macroscopic model are supplied by solving the microscopic model on a sparse spatial domain. The generated code is verified by applying the linearization model of the Richards' equation. Considering two different constitutive relationships, this method is applied to several test examples with different soil textures and boundary conditions. Both the Dirichlet and the periodic boundary conditions are considered for solving the local microscopic model when the water flow in heterogeneous unsaturated soils is simulated by FDHMM. The numerical experiments demonstrate that FDHMM can effectively simulate the transient unsaturated water flow in the specific soils. The numerical experiments also demonstrate that FDHMM can achieve accurate global mass balance and is a globally convergent algorithm, and the spatial correlation length of random coefficients under the specific standard deviation has relatively little influence on the accuracy of the method.
Modeling of gas‐driven magmatic overturn: Tracking of phenocryst dispersal and gathering during magma mixing
Authors: Ruprecht Philipp , Bergantz George W. , Dufek Josef
Published: July 2008

We present a combined multiphase numerical and crystal‐tracking approach that provides a framework to investigate the transport and zoning of crystals associated with a gas‐driven mixing event. Mixing in compositionally intermediate to silicic magmatic systems is often initiated by gas exsolution in the recharging magma, causing a density inversion and subsequent overturn. The overturn is simulated for a range of bubble volume fractions ɛbubbles and therefore indirectly for a range of Reynolds numbers Re. All simulations show chaotic flow dynamics with fast overturn timescales of minutes to hours. The large‐scale mixing is inefficient during a single overturn, resulting in a continuously stratified system with respect to bubble volume fraction. The crystal‐tracking algorithm provides us with information on the small scales, i.e., 10 cm. On this length scale we observe gathering of different crystals during the overturn that typically ranges on the order of tens of meters. Thus, a complex crystal population may arise within a single overturn. This gathering and dispersal of crystals is strongest and most uniform for high Re. For low Re, crystal populations are characterized by less gathering of crystals that originated from distal portions of the magma body. During the overturn the crystals pass through environments of changing chemical potential. We apply the Damköhler number Da, which compares the crystallization or dissolution to the advection timescale. Results show an asymmetry between crystallization and dissolution. Crystallization times are too slow during gas‐driven overturn to record transient changes in chemical potential. Crystals most likely only record their initial as well as their final chemical environment. In contrast, dissolution and advection rates are of similar order, suggesting potential dissolution during the overturn. On the basis of the results for gas‐driven overturn we expect that slower physical mixing processes may be continuously recorded in the zonation pattern of the crystal phases as long as the changes in chemical potential produce crystal growth.
Cassini detection of water‐group pick‐up ions in the Enceladus torus
Authors: Tokar R. L. , Wilson R. J. , Johnson R. E. , Henderson M. G. , Thomsen M. F. , Cowee M. M. , Sittler E. C. , Young D. T. , Crary F. J. , McAndrews H. J. , Smith H. T.
Published: July 2008

This study reports direct detection by the Cassini plasma spectrometer of freshly‐produced water‐group pick‐up ions within the proposed Enceladus torus, a radially narrow toroidal region surrounding Saturn that contains a high density of water‐group neutrals. This torus is produced by the icy plumes observed near the south pole of Enceladus. The ions are created by charge exchange collisions between water‐group neutrals in the Enceladus torus and thermal ions corotating with Saturn. They are identified in the Cassini data via their characteristic ring‐like signatures in ion velocity distributions. In the radial distance range of 4.0 to 4.5 RS, the density of these non‐thermalized ions is estimated to be at least 5.2 cm−3, about 8% of the total ion density. The estimated density together with ionization, charge exchange, and loss times, yield an ion thermalization time of at least 3150 s, in reasonable agreement with hybrid particle simulations.
Lack of Sex-Linked Differences in Cerebral Edema and Aquaporin-4 Expression after Experimental Stroke
Authors: Liu Xiaoqin , Zhang Wenri , Alkayed Nabil J , Froehner Stanley C , Adams Marvin E , Amiry-Moghaddam Mahmood , Ottersen Ole Petter , Hurn Patricia D , Bhardwaj Anish
Published: July 2008

Aquaporin-4 (AQP4) has been shown to be important in the evolution of stroke-associated cerebral edema. However, the role of AQP4 in stroke-associated cerebral edema as it pertains to sex has not been previously studied. The perivascular pool of AQP4 is important in the influx and efflux of water during focal cerebral ischemia. We used mice with targeted disruption of the gene encoding α-syntrophin (α-Syn−/−) that lack the perivascular AQP4 pool but retain the endothelial pool of this protein. Infarct volume at 72 h after transient focal ischemia (90 mins) in isoflurane-anesthetized mice was attenuated in both sexes with α-Syn deletion as compared with their wild-type (WT) counterparts. There were no sex differences in hemispheric water content in WT and α-Syn−/− mice or regional AQP4 expression in WT mice. In neither sex did α-Syn deletion lead to alterations in end-ischemic regional cerebral blood flow (rCBF). These data suggest that after experimental stroke: (1) there is no difference in stroke-associated cerebral edema based on sex, (2) AQP4 does not involve in sex-based differences in stroke volume, and (3) perivascular pool of AQP4 has no significant role in end-ischemic rCBF.
The Neuroprotective Effect of Prostaglandin E2 EP1 Receptor Inhibition has a Wide Therapeutic Window, is Sustained in Time and is not Sexually Dimorphic
Authors: Abe Takato , Kunz Alexander , Shimarnura Munehisa , Zhou Ping , Anrather Josef , Iadecola Costantino
Published: July 2008

We investigated the preclinical characteristics of the neuroprotective effect of the prostaglandin E2 type 1 receptor (EP1) antagonist SC51089 in models of focal cerebral ischemia produced by occlusion of the mouse middle cerebral artery (MCA). We found that systemic administration of SC51089 (5 to 20 μg/kg; i.p.) reduces the brain injury produced by transient (−50% ± 8%; n = 12; P < 0.05) or permanent (−39% ± 7%; n = 12; P < 0.05) MCA occlusion. SC51089 was effective even when administered up to 12 h after ischemia. The protective effect was observed both in male and female mice and was sustained for at least 2 weeks after induction of ischemia. The reduction in injury volume was associated with an improvement in neurological function assessed by the Bederson deficit score, the hanging wire test and the corner test. The data provide proof of principle that EP1 receptor inhibition is a potentially valuable strategy for neuroprotection that deserves further preclinical investigation for therapeutic application in human stroke.
The 5′–3′ exoribonuclease Pacman is required for normal male fertility and is dynamically localized in cytoplasmic particles in Drosophila testis cells
Authors: Zabolotskaya Maria V. , Grima Dominic P. , Lin Ming-Der , Chou Tze-Bin , Newbury Sarah F.
Published: July 2008

The exoribonuclease Xrn1 is widely recognised as a key component in the 5′–3′ RNA degradation pathway. This enzyme is highly conserved between yeast and humans and is known to be involved in RNA interference and degradation of microRNAs as well as RNA turnover. In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place. In this paper we show for the first time that Pacman, the Drosophila homologue of Xrn1, is localized in cytoplasmic particles in Drosophila testis cells. These particles are present in both the mitotically dividing spermatogonia derived from primordial stem cells and in the transcriptionally active spermatocytes. Pacman is co-localized with the decapping activator dDcp1 and the helicase Me31B (a Dhh1 homologue) in these particles, although this co-localization is not completely overlapping, suggesting that there are different compartments within these granules. Particles containing Pacman respond to stress and depletion of 5′–3′ decay factors in the same way as yeast P-bodies, and therefore are likely to be sites of mRNA degradation or storage. Pacman is shown to be required for normal Drosophila spermatogenesis, suggesting that control of mRNA stability is crucial in the testis differentiation pathway.
The angiotensin-converting enzyme insertion/deletion polymorphism is associated with phagocytic NADPH oxidase-dependent superoxide generation: potential implication in hypertension
Authors: San José Gorka , Fortuño Ana , Moreno María U. , Robador Pablo A. , Bidegain Julen , Varo Nerea , Beloqui Oscar , Díez Javier , Zalba Guillermo
Published: July 2008

The objective of the present study was to analyse the influence of the ACE (angiotensin-converting enzyme) gene I/D (insertion/deletion) polymorphism on NADPH oxidase-dependent O2•− (superoxide radical) production, and to investigate the clinical implication of this association in hypertensive subjects. A case-control study was performed in a random sample of the general population composed of 189 normotensive subjects and 223 hypertensive subjects. The ACE polymorphism was determined by PCR. NADPH oxidase-dependent O2•− production was quantified in phagocytic cells by chemiluminescence. MMP-9 (matrix metalloproteinase-9), a marker of atherosclerosis previously reported to be associated with NADPH oxidase overactivity, was quantified by ELISA in plasma samples. The distribution of genotypes was in Hardy–Weinberg equilibrium. The I/D polymorphism was not associated with hypertension. NADPH oxidase-dependent O2•− production was significantly higher in D/D (deletion/deletion) than in I/I (insertion/insertion) and I/D, both in normotensive and hypertensive subjects. Interestingly, plasma levels of angiotensin II were significantly higher in D/D than in I/I and I/D, both in normotensive and hypertensive subjects. Plasma levels of MMP-9 and systolic blood pressure values were significantly higher in D/D than in I/I and I/D hypertensive subjects, whereas no differences were found among genotypes in normotensive subjects. Interestingly, NADPH oxidase-dependent O2•− production positively associated with plasma MMP-9 levels in hypertensive subjects, which remained significant after adjustment for age and gender. In conclusion, in the present study we have reported for the first time an association of the D/D genotype of the ACE I/D polymorphism with phagocytic NADPH oxidase-mediated O2•− overproduction. Within the group of hypertensive patients, D/D cases also associated with increased blood pressure values and with enhanced plasma levels of MMP-9.
Gender and renal function influence plasma levels of copeptin in healthy individuals
Authors: Bhandari Sanjay S. , Loke Ian , Davies Joan E. , Squire Ian B. , Struck Joachim , Ng Leong L.
Published: July 2008

The present study sought to identify confounding factors for the interpretation of copeptin levels in healthy individuals. The natriuretic peptides are recognized as diagnostic and prognostic tools in HF (heart failure). Interpretation of BNP (brain natriuretic peptide) and NTproBNP (N-terminal pro-BNP) levels is multifaceted as their secretion is influenced by many variables. A newly identified glycopeptide called copeptin is comparable with the natriuretic peptides in the diagnosis and prognosis of HF and as a prognostic biomarker after AMI (acute myocardial infarction). Copeptin, derived from the C-terminal portion of the precursor to AVP (arginine vasopressin), is secreted stoichiometrically with vasopressin, hence it can be used as a surrogate marker of the AVP system. In the present study, 706 healthy volunteers were recruited from a local HF screening study. Participants with a history of cardiovascular disease and those with echocardiographic abnormalities were excluded from the study. Copeptin and NTproBNP levels were assayed using in-house immunoluminometric assays. Median copeptin levels were significantly higher in the male volunteers compared with the females [median (range): 4.3 (0.4–44.3) compared with 3.2 (1.0–14.8) pmol/l; P<0.001]. In males, copeptin was correlated with eGFR (estimated glomerular filtration rate; rs=−0.186, P<0.001). In females, the correlation of copeptin with eGFR was weak (rs=−0.097, P=0.095). DT (deceleration time) and left atrial size correlated with higher copeptin levels (rs=0.085, P=0.029 and rs=0.206, P<0.001 respectively). Only gender (P<0.001), eGFR (P<0.001), left atrial size (P=0.04) and DT (P=0.02) remained independently predictive of plasma copeptin. The present study suggests that gender and renal function specific partition values should be used to interpret copeptin values in future studies of this biomarker in HF or ischaemic heart disease.
Morphological and molecular variation in Conospermum triplinervium (Proteaceae), the tree smokebush: implications for bushland restoration
Authors: Sinclair Elizabeth , Cheetham Belinda , Krauss Siegfried , Hobbs Richard
Published: July 2008

Ecological restoration benefits from information on population genetic structure and variation within a species to make informed decisions on where to source material of the local genetic provenance. Conospermum triplinervium is extremely rare in Bold Park, a large bushland remnant currently undergoing restoration in Perth, Western Australia. We sampled plants from Bold Park and six other native populations across the northern half of the species’ range to assess patterns of morphological and genetic variation. There was considerable variation across six leaf measures with significant differentiation among some populations. The molecular data showed a high level of population structure (ΘB = 0.4974), with varying degrees of spatial overlap among populations in an ordination plot. Significant differentiation was observed among all pairs of populations, except for Bold Park and its geographically closest populations at Kings Park and Neerabup. These two populations had greater genetic variation (50.9% and 54.5% polymorphic markers, respectively) than did that at Bold Park (20.2%). The small Bold Park population would benefit from augmentation (via cuttings) from local plants. However, in the longer term, should the Bold Park population show evidence of declining viability, then material should be sourced from the genetically similar Kings Park population to increase genetic variation whilst also maintaining genetic integrity.
Plant trait - environmental linkages among contrasting landscapes and climate regimes in temperate eucalypt woodlands
Authors: Wills Karen E. , Clarke Peter J.
Published: July 2008

Ecological sorting of species along climate and landscape gradients is a fundamental global pattern. However, the extent to which functional traits reflect floristic turnover in response to interactions between climate and landscape gradients is rarely assessed. We tested whether floristic variation among sites within a bioregion was more strongly correlated with soil fertility or climate. We then examined the relationship between floristic composition, environment and the co-variation of selected vegetative and regenerative functional traits. This allowed us to assess the ecological sorting of species along soil fertility and rainfall gradients and to detect any resource compensation effects via interactions between these factors. Floristic differences were equally associated with soil fertility and climate contrasts but species’ trait patterns were more strongly associated with soil fertility than rainfall. No interactive effects, which would suggest resource compensation, were detected. Instead, more fertile sites consistently had more forbs, annuals and grasses in comparison with less fertile sites which were dominated by woody species and had a higher abundance of graminoids. Three broad mechanisms for sorting of species based on trait patterns are proposed (1) differences in the fundamental regenerative and growth niche, (2) resource competition during establishment and (3) disturbance-mediated sorting.
Water relations and mineral nutrition of Triodia grasses on desert dunes and interdunes
Authors: Grigg Alasdair M. , Veneklaas Erik J. , Lambers Hans
Published: July 2008

Desert dunes and interdunes provide habitat heterogeneity and profoundly influence the spatial and temporal distribution of water and nutrients throughout the landscape. These underlying physical processes shape the plant species composition and their ecophysiology. Spinifex grasses dominate the vegetation throughout much of Australia and are categorised into two groups; ‘soft’ species occur mostly in northern, subtropical to semiarid regions, whereas ‘hard’ species occur mostly throughout the dry centre and southern interior. This study examined the water and nutrient relations and leaf anatomy of dominant ‘soft’ and ‘hard’ spinifex in the Great Sandy Desert, where their distributions overlap. The ‘soft’ species, Triodia schinzii (Henrard) Lazarides, occurs only on sand dunes, whereas the ‘hard’ species, T. basedowii E.Pritz., is restricted to the flat interdunes. We proposed two hypotheses: 1) that the dune species, T. schinzii would display more favourable water status and 2) the interdune species, T. basedowii would display higher leaf nutrient concentrations. Triodia schinzii displayed significantly less negative leaf water potentials at predawn and at midday (–0.4 and –2.0 MPa, respectively) than T. basedowii (–0.9 and –3.0 MPa, respectively) throughout the middle of the dry season. Photosynthesis rates were also significantly higher in T. schinzii than T. basedowii in the wet season (140 v. 84 nmol g–1 s–1), but there were no significant differences between species in leaf conductance. Leaf δ13C composition confirmed anatomical observations that both species were C4 and supported the finding that T. schinzii displayed significantly greater photosynthetic water-use efficiency during the wet season than T. basedowii. In general, foliar nutrient concentrations were not significantly different between species; however, both species exhibited especially low leaf P and to a lesser extent N. We conclude that water is more readily available in the dune than the interdune as a result of greater soil depth and associated water storage capacity. These properties are considered the main factors influencing plant species distribution. Given the climatic and geographic distribution of these two Triodia species, it is suggested that sand dunes provide a mesic corridor for T. schinzii to extend its range from higher rainfall areas into the arid interior.
Chloroplast Fe(III) chelate reductase activity is essential for seedling viability under iron limiting conditions
Authors: Jeong Jeeyon , Cohu Christopher , Kerkeb Loubna , Pilon Marinus , Connolly Erin L. , Guerinot Mary Lou
Published: July 2008

Photosynthesis, heme biosynthesis, and Fe-S cluster assembly all take place in the chloroplast, and all require iron. Reduction of iron via a membrane-bound Fe(III) chelate reductase is required before iron transport across membranes in a variety of systems, but to date there has been no definitive genetic proof that chloroplasts have such a reduction system. Here we report that one of the eight members of the
Arabidopsis
ferric reductase oxidase (FRO) family, FRO7, localizes to the chloroplast. Chloroplasts prepared from
fro7
loss-of-function mutants have 75% less Fe(III) chelate reductase activity and contain 33% less iron per microgram of chlorophyll than wild-type chloroplasts. This decreased iron content is presumably responsible for the observed defects in photosynthetic electron transport. When germinated in alkaline soil,
fro7
seedlings show severe chlorosis and die without setting seed unless watered with high levels of soluble iron. Overall, our results provide molecular evidence that FRO7 plays a role in chloroplast iron acquisition and is required for efficient photosynthesis in young seedlings and for survival under iron-limiting conditions.
Protecting residential care facilities from pandemic influenza
Authors: Nuño M. , Reichert T. A. , Chowell G. , Gumel A. B.
Published: July 2008

It is widely believed that protecting health care facilities against outbreaks of pandemic influenza requires pharmaceutical resources such as antivirals and vaccines. However, early in a pandemic, vaccines will not likely be available and antivirals will probably be of limited supply. The containment of pandemic influenza within acute-care hospitals anywhere is problematic because of open connections with communities. However, other health care institutions, especially those providing care for the disabled, can potentially control community access. We modeled a residential care facility by using a stochastic compartmental model to address the question of whether conditions exist under which nonpharmaceutical interventions (NPIs) alone might prevent the introduction of a pandemic virus. The model projected that with currently recommended staff–visitor interactions and social distancing practices, virus introductions are inevitable in all pandemics, accompanied by rapid internal propagation. The model identified staff reentry as the critical pathway of contagion, and provided estimates of the reduction in risk required to minimize the probability of a virus introduction. By using information on latency for historical and candidate pandemic viruses, we developed NPIs that simulated notions of protective isolation for staff away from the facility that reduced the probability of bringing the pandemic infection back to the facility to levels providing protection over a large range of projected pandemic severities. The proposed form of protective isolation was evaluated for social plausibility by collaborators who operate residential facilities. It appears unavoidable that NPI combinations effective against pandemics more severe than mild imply social disruption that increases with severity.
D-retrovirus morphogenetic switch driven by the targeting signal accessibility to Tctex-1 of dynein
Authors: Vlach Jiří , Lipov Jan , Rumlová Michaela , Veverka Václav , Lang Jan , Srb Pavel , Knejzlík Zdeněk , Pichová Iva , Hunter Eric , Hrabal Richard , Ruml Tomáš
Published: July 2008

Despite extensive data demonstrating that immature retroviral particle assembly can take place either at the plasma membrane or at a distinct location within the cytoplasm, targeting of viral precursor proteins to either assembly site still remains poorly understood. Biochemical data presented here suggest that Tctex-1, a light chain of the molecular motor dynein, is involved in the intracellular targeting of Mason–Pfizer monkey virus (M-PMV) polyproteins to the cytoplasmic assembly site. Comparison of the three-dimensional structures of M-PMV wild-type matrix protein (wt MA) with a single amino acid mutant (R55F), which redirects assembly from a cytoplasmic site to the plasma membrane, revealed different mutual orientations of their C- and N-terminal domains. This conformational change buries a putative intracellular targeting motif located between both domains in the hydrophobic pocket of the MA molecule, thereby preventing the interaction with cellular transport mechanisms.
Tropism-independent protection of macaques against vaginal transmission of three SHIVs by the HIV-1 fusion inhibitor T-1249
Authors: Veazey Ronald S. , Ketas Thomas A. , Klasse Per Johan , Davison Donna K. , Singletary Morgan , Green Linda C. , Greenberg Michael L. , Moore John P.
Published: July 2008

We have assessed the potential of the fusion inhibitory peptide T-1249 for development as a vaginal microbicide to prevent HIV-1 sexual transmission. When formulated as a simple gel, T-1249 provided dose-dependent protection to macaques against high-dose challenge with three different SHIVs that used either CCR5 or CXCR4 for infection (the R5 virus SHIV-162P3, the X4 virus SHIV-KU1 and the R5X4 virus SHIV-89.6P), and it also protected against SIVmac251 (R5). Protection of half of the test animals was estimated by interpolation to occur at T-1249 concentrations of ≈40–130 μM, whereas complete protection was observed at 0.1–2 mM.
In vitro
, T-1249 had substantial breadth of activity against HIV-1 strains from multiple genetic subtypes and in a coreceptor-independent manner. Thus, at 1 μM in a peripheral blood mononuclear cell-based replication assay, T-1249 inhibited all 29 R5 viruses, all 12 X4 viruses and all 7 R5X4 viruses in the test panel, irrespective of their genetic subtype. Combining lower concentrations of T-1249 with other entry inhibitors (CMPD-167, BMS-C, or AMD3465) increased the proportion of test viruses that could be blocked. In the PhenoSense assay, T-1249 was active against 636 different HIV-1 Env-pseudotyped viruses of varying tropism and derived from clinical samples, with IC
50
values typically clustered in a 10-fold range ≈10 nM. Overall, these results support the concept of using T-1249 as a component of an entry inhibitor-based combination microbicide to prevent the sexual transmission of diverse HIV-1 variants.
A knowledge-based approach to predict intragenic deletions or duplications
Authors: Kalari Krishna R. , Casavant Thomas L. , Scheetz Todd E.
Published: July 2008

Motivation: Despite recent improvements in high-throughput or classic molecular biology approaches it is still challenging to identify intermediate resolution genomic variations (50 bp to 50 kb). Although array-based technologies can be used to detect copy number variations in the human genome they are biased to detect only the largest such deletions or duplications. Several studies have identified deletions or duplications occurring within a gene that directly cause or predispose to disease. We have developed a novel computational system, SPeeDD (system to prioritize deletions or duplications) that utilizes machine learning techniques to predict likely candidate regions that delete or duplicate exon(s) within a gene.

Results: Data mining and machine learning methods were applied to identify sequence features that were predictive of homologous recombination events. The logistic model tree (LMT) method yielded the best results. Sensitivity varied from 20% to 71.6% depending on the specific machine learning model used, but specificity exceeded 90% for all methods evaluated. In addition, the SPeeDD system successfully predicted and prioritized a recently published novel BRCA1 mutation.

Conclusions: Results suggest that the SPeeDD system is effective at prioritizing candidate deletions and duplications within a gene. Use of SPeeDD enables more focused screening, which reduces the labor and associated costs of the molecular assays and may also lead to targeted design of new array-based screens to focus on candidate areas to accelerate the process of mutation discovery.

Contact:  tscheetz@eng.uiowa.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
The combined role of wear particles, macrophages and lymphocytes in the loosening of total joint prostheses
Authors: Revell Peter A
Published: July 2008

This review considers the causes of loosening of prosthetic joint replacement paying attention to the biological mechanisms rather than other effects that are physical, such as component fracture and other failure related to mechanical problems. Infection accounts for approximately 1.5 per cent of joint loosening and when it occurs it is a cause of serious concern to the surgeon. The loosening of prosthetic joints in the absence of infection is by far the most common reason for revision surgery and is known as aseptic loosening. While this may be multifactorial in terms of causation, and non-biological factors may contribute significantly in a particular individual, a significant part is undoubtedly played by the generation of wear debris, mainly from the bearing surfaces of the joint, and the cellular reaction to this in the implant bed. Phagocytic cells (macrophages and multinucleated giant cells) are the ones that remove foreign material from the tissues, and the ways in which these cells function in the interface between implant and bone are described. Mediators produced locally include numerous cytokines, enzymes and integrins. There is evidence for interactions between macrophages and locally recruited lymphocytes, which may or may not give rise to an immunologically mediated process.

Sensitization of individuals having metal implants in place has been shown by positive skin tests or blood lymphocyte transformation tests and in these cases has been accompanied by loosening and failure of the replacement joint. The question remains as to whether this process is also present in a proportion of individuals with aseptic loosening in the absence of clearly defined clinical evidence of sensitization.

Numerous studies performed by the author's group and, latterly, by others suggest that the cellular reactions detected in the tissues in cases of aseptic loosening are indeed those of contact sensitization. There is good evidence to show that a type IV cell-mediated immune reaction is taking place, with TH1 cell involvement and active antigen presentation. The extent to which sensitization is present in individual cases of aseptic loosening remains a subject for further work and this needs all the sophisticated molecular methods now available to modern biology to be applied in appropriate prospective clinical studies coupled with experimental modelsin vitroandin vivo. Immunological processes may play a more important part in joint loosening than previously considered.
Programming with models: modularity and abstraction provide powerful capabilities for systems biology
Authors: Mallavarapu Aneil , Thomson Matthew , Ullian Benjamin , Gunawardena Jeremy
Published: July 2008

Mathematical models are increasingly used to understand how phenotypes emerge from systems of molecular interactions. However, their current construction as monolithic sets of equations presents a fundamental barrier to progress. Overcoming this requires modularity, enabling sub-systems to be specified independently and combined incrementally, and abstraction, enabling generic properties of biological processes to be specified independently of specific instances. These, in turn, require models to be represented as programs rather than as datatypes. Programmable modularity and abstraction enables libraries of modules to be created, which can be instantiated and reused repeatedly in different contexts with different components. We have developed a computational infrastructure that accomplishes this. We show here why such capabilities are needed, what is required to implement them and what can be accomplished with them that could not be done previously.
Preparation of suspensions of phospholipid-coated microbubbles by coaxial electrohydrodynamic atomization
Authors: Farook U , Stride E , Edirisinghe M.J
Published: July 2008

The use of phospholipid-coated microbubbles for medical applications is gaining considerable attention. However, the preparation of lipid-coated microbubble suspensions containing the ideal size and size distribution of bubbles still represents a considerable challenge. The most commonly used preparation methods of sonication and mechanical agitation result in the generation of polydisperse microbubbles with diameters ranging from less than 1 μm to greater than 50 μm. Efforts have been made via distinctly different techniques such as microfluidic and electrohydrodynamic bubbling to prepare lipid-coated microbubbles with diameters less than 10 μm and with a narrow size distribution, and recent results have been highly promising. In this paper, we describe a detailed investigation of the latter method that essentially combines liquid and air flow, and an applied electric field to generate microbubbles. A parametric plot was constructed between the air flow rate (
Q
g
) and the lipid suspension flow rate (
Q
l
) to identify suitable flow rate regimes for the preparation of phospholipid-coated microbubbles with a mean diameter of 6.6 μm and a standard deviation of 2.5 μm. The parametric plot has also helped in developing a scaling equation between the bubble diameter and the ratio
Q
g
/
Q
l
. At ambient temperature (22°C), these bubbles were very stable with their size remaining almost unchanged for 160 min. The influence of higher temperatures such as the human body temperature (37°C) on the size and stability of the microbubbles was also explored. It was found that the mean bubble diameter fell rapidly to begin with but then stabilized at 1–2 μm after 20 min.
Complementary vasoactivity and matrix remodelling in arterial adaptations to altered flow and pressure
Authors: Valentín A , Cardamone L , Baek S , Humphrey J.D
Published: July 2008

Arteries exhibit a remarkable ability to adapt to sustained alterations in biomechanical loading, probably via mechanisms that are similarly involved in many arterial pathologies and responses to treatment. Of particular note, diverse data suggest that cell and matrix turnover within vasoaltered states enables arteries to adapt to sustained changes in blood flow and pressure. The goal herein is to show explicitly how altered smooth muscle contractility and matrix growth and remodelling work together to adapt the geometry, structure, stiffness and function of a representative basilar artery. Towards this end, we employ a continuum theory of constrained mixtures to model evolving changes in the wall, which depend on both wall shear stress-induced changes in vasoactive molecules (which alter smooth muscle proliferation and synthesis of matrix) and intramural stress-induced changes in growth factors (which alter cell and matrix turnover). Simulations show, for example, that such considerations help explain the different rates of experimentally observed adaptations to increased versus decreased flows as well as differences in rates of change in response to increased flows or pressures.
Exceptionally preserved lacustrine ostracods from the Middle Miocene of Antarctica: implications for high-latitude palaeoenvironment at 77° south
Authors: Williams Mark , Siveter David J , Ashworth Allan C , Wilby Philip R , Horne David J , Lewis Adam R , Marchant David R
Published: July 2008

A newly discovered Konservat-Lagerstätte from the Middle Miocene of the western Olympus Range, Dry Valleys, Antarctica, yields cypridoidean ostracods complete with preserved body and appendages. This is the first record of three-dimensionally fossilized animal soft tissues from the continent. The ostracods are preserved in goethite, secondary after pyrite, representing a novel mode of exceptional preservation. They signal a high-latitude (greater than 77° south) lake setting (Palaeolake Boreas) viable for benthic animal colonization prior to 14 Myr ago. Their presence supports the notion of warmer, tundra-like environmental conditions persisting in the Dry Valleys until the Middle Miocene.
Mutual information reveals variation in temperature-dependent sex determination in response to environmental fluctuation, lifespan and selection
Authors: Schwanz Lisa E , Proulx Stephen R
Published: July 2008

Quantifying the degree to which sex determination depends on the environment can yield insight into the evolution, ecological dynamics, and functional aspects of sex determination. In temperature-dependent sex determination (TSD), theory often predicts a complete dependence of sex on temperature, with a switch-like reaction norm. However, empirical data suggest more shallow relationships between sex and temperature. Here, we demonstrate the usefulness of an index, mutual information (MI), to reflect the degree of temperature dependence in sex. MI depends on both the shape of a reaction norm and the natural temperature variation, thus providing a measure of TSD that is ecologically dependent. We demonstrate that increased lifespan and decreased environmental fluctuation predict reaction norms with high MI (switch-like). However, mutation and weaker selection on sex-specific performance reduce average MI in a population, suggesting that mutation–selection balance can resolve some of the conflict between theoretical predictions of individual-based optimality and population-based empirical results. The MI index allows clear comparison of TSD across life histories and habitats and reveals functional similarities between reaction norms that may appear different. The model provides testable predictions for TSD across populations, namely that MI should increase with lifespan and decrease with historical environmental fluctuations.
Starving the competition: a proximate cause of reproductive skew in burying beetles (Nicrophorus vespilloides)
Authors: Eggert Anne-Katrin , Otte Tobias , Müller Josef K
Published: July 2008

Proximate mechanisms underlying reproductive skew are obscure in many animals that breed communally. Here, we address causes of reproductive skew in brood-parasitic associations of burying beetles (Nicrophorus vespilloides). Male and female burying beetles feed and defend their larvae on buried carcasses. When several females locate the same small carcass, they engage in violent physical altercations. The subordinate then acts as an intraspecific brood parasite, laying eggs, but not providing care. The dominant female largely monopolizes access to the carcass; she alone provides parental care and her share of the brood is much larger than the subordinate's. On larger carcasses, subordinates have greater access to the carcass than on small ones, and reproductive skew is reduced. Differential fecundity, ovicide and larvicide have been suggested as causes of skew on small carcasses. Here, we report the results of the experiments pertaining to the first two of these potential mechanisms. Ovicide did not significantly contribute to reproductive skew on small carcasses, but differential fecundity did. Fecundity differences were due to dominance status, not body sizeper se. Fecundity differences disappeared when supplemental food was available, suggesting that reduced access to the carcass limits fecundity by causing nutritional deficiencies. Supplemental food prevented such nutritional deficiencies and allowed subordinates to produce as many eggs as dominants. Apparently, aggressive behaviour by dominants functions in the context of reproductive competition, limiting subordinate reproduction by preventing food intake on the carcass.
Association between self‐report pain ratings of child and parent, child and nurse and parent and nurse dyads: meta‐analysis
Authors: Zhou Huaqiong , Roberts Pam , Horgan Louise
Published: July 2008

Title.  Association between self‐report pain ratings of child and parent, child and nurse and parent and nurse dyads: meta‐analysis.

Aim.  This paper is a report of a meta‐analysis to investigate the association between self‐report pain ratings for the dyads of child and parent, child and nurse and parent and nurse.

Background.  Existing research has shown conflicting results with regard to agreements of self‐report pain ratings between the three dyads.

Data sources.  The CINAHL, Medline, Ovid and PsycINFO databases were searched using keyword, such as ‘children/adolescents’, ‘parents/nurses’, ‘pain assessment’, ‘pain ratings’, ‘association’ and ‘agreement’. Studies published in English in or after 1990 were included.

Methods.  Meta‐analysis methodology was applied to 12 pain assessment studies published between 1990 and 2007 which met the inclusion criteria. In the 12 studies a common effect size was estimated using the Pearson’s correlation coefficient. Therefore, a fixed‐effects model was chosen for this meta‐analysis.

Results.  We found moderate summary effect sizes between self‐reported pain ratings for the dyad of child and parent (r = 0·64) and the child and nurse dyad (r = 0·58) and a weak summary effect size of r = 0·49 for the dyad of parent and nurse. The summarized effect sizes for each of the three dyads varied across the studies. A test of homogeneity (Q‐statistic) indicated that all effect size estimates were not homogeneous.

Conclusion.  Parents’ and nurses’ perceptions of children’s pain should only be considered as estimates rather than expressions of the pain experienced, and not the same as children’s self‐reports. There is a need for education on selection of appropriate pain assessment scales in relation to the age and development of the child.
Defying all odds: coping with the challenges of volunteer caregiving for patients with AIDS in South Africa
Authors: Akintola Olagoke
Published: July 2008

Title.  Defying all odds: coping with the challenges of volunteer caregiving for patients with AIDS in South Africa.

Aim.  This paper is a report of a study to explore the challenges experienced by volunteer caregivers of people living with HIV/AIDS and the strategies employed in coping with these challenges.

Background.  Informal caregiving is associated with stresses that often results in poor health outcomes for caregivers. In South Africa, volunteers play a major role in the provision of care for people living with HIV/AIDS and have been shown to experience burdens as a result of caring. However, little is known about stress and coping among volunteer caregivers.

Methods.  An ethnographic study was conducted, using observation and in‐depth interviews, to collect data with 20 volunteers and other stakeholders in two semi‐rural communities in South Africa over a 19‐month period in 2002/2003.

Findings.  ‘Defying all odds’ emerged as the central theme that encompassed the various ways in which volunteer caregivers dealt with the many practical challenges confronting them. These challenges initially posed a threat to volunteering work but were gradually appraised by volunteers as challenges that could be dealt with using various strategies in order to continue providing care. Eight themes highlighting these challenges and the coping strategies employed by volunteers were identified.

Conclusion.  A clear understanding of how volunteers deal with challenges of caring for people living with HIV/AIDS can give insight into their weaknesses and strengths and can inform the design of interventions aimed at providing support. Studies are needed to facilitate better understanding of the processes of appraisal of challenges by volunteers and the effectiveness of coping strategies, and to track coping strategies over time.