Top-down systems biology modeling of host metabotype-microbiome associations in obese rodents

Covariation in the structural composition of the gut microbiome and the spectroscopically derived metabolic phenotype (metabotype) of a rodent model for obesity were investigated using a range of multivariate statistical tools. Urine and plasma samples from three strains of 10-week-old male Zucker rats (obese (fa/fa, n = 8), lean (fal-, n = 8) and lean (-/-, n = 8)) were characterized via high-resolution H-1 NMR spectroscopy, and in parallel, the fecal microbial composition was investigated using fluorescence in situ hydridization (FISH) and denaturing gradient gel electrophoresis (DGGE) methods. All three Zucker strains had different relative abundances of the dominant members of their intestinal microbiota (FISH), with the novel observation of a Halomonas and a Sphingomonas species being present in the (fa/fa) obese strain on the basis of DGGE data. The two functionally and phenotypically normal Zucker strains (fal- and -/-) were readily distinguished from the (fa/fa) obese rats on the basis of their metabotypes with relatively lower urinary hippurate and creatinine, relatively higher levels of urinary isoleucine, leucine and acetate and higher plasma LDL and VLDL levels typifying the (fa/fa) obese strain. Collectively, these data suggest a conditional host genetic involvement in selection of the microbial species in each host strain, and that both lean and obese animals could have specific metabolic phenotypes that are linked to their individual microbiomes.

Workflow-oriented collaborative grid portals

The paper presents how workflow-oriented, single-user Grid portals could be extended to meet the requirements of users with collaborative needs. Through collaborative Grid portals different research and engineering teams would be able to share knowledge and resources. At the same time the workflow concept assures that the shared knowledge and computational capacity is aggregated to achieve the high-level goals of the group. The paper discusses the different issues collaborative support requires from Grid portal environments during the different phases of the workflow-oriented development work. While in the design period the most important task of the portal is to provide consistent and fault tolerant data management, during the workflow execution it must act upon the security framework its back-end Grids are built on.

Equitability revisited: why the “equitable threat score” is not equitable

In the forecasting of binary events, verification measures that are “equitable” were defined by Gandin and Murphy to satisfy two requirements: 1) they award all random forecasting systems, including those that always issue the same forecast, the same expected score (typically zero), and 2) they are expressible as the linear weighted sum of the elements of the contingency table, where the weights are independent of the entries in the table, apart from the base rate. The authors demonstrate that the widely used “equitable threat score” (ETS), as well as numerous others, satisfies neither of these requirements and only satisfies the first requirement in the limit of an infinite sample size. Such measures are referred to as “asymptotically equitable.” In the case of ETS, the expected score of a random forecasting system is always positive and only falls below 0.01 when the number of samples is greater than around 30. Two other asymptotically equitable measures are the odds ratio skill score and the symmetric extreme dependency score, which are more strongly inequitable than ETS, particularly for rare events; for example, when the base rate is 2% and the sample size is 1000, random but unbiased forecasting systems yield an expected score of around −0.5, reducing in magnitude to −0.01 or smaller only for sample sizes exceeding 25 000. This presents a problem since these nonlinear measures have other desirable properties, in particular being reliable indicators of skill for rare events (provided that the sample size is large enough). A potential way to reconcile these properties with equitability is to recognize that Gandin and Murphy’s two requirements are independent, and the second can be safely discarded without losing the key advantages of equitability that are embodied in the first. This enables inequitable and asymptotically equitable measures to be scaled to make them equitable, while retaining their nonlinearity and other properties such as being reliable indicators of skill for rare events. It also opens up the possibility of designing new equitable verification measures.

Modified level set method with Canny operator for image noise removal

The level set method is commonly used to address image noise removal. Existing studies concentrate mainly on determining the speed function of the evolution equation. Based on the idea of a Canny operator, this letter introduces a new method of controlling the level set evolution, in which the edge strength is taken into account in choosing curvature flows for the speed function and the normal to edge direction is used to orient the diffusion of the moving interface. The addition of an energy term to penalize the irregularity allows for better preservation of local edge information. In contrast with previous Canny-based level set methods that usually adopt a two-stage framework, the proposed algorithm can execute all the above operations in one process during noise removal.

Quantitation of apolipoprotein B-48 in triacylglycerol-rich lipoproteins by a specific enzyme-linked immunosorbent assay

This paper describes the use of an antiserum, specific for apolipoprotein (apo) B-48, in a competitive, enzyme-linked immunosorbent assay (ELISA) for apo B-48 in triacylglycerol-rich lipoprotein (TRL) fractions prepared from fasting and post-prandial plasma samples. Previously we showed the antiserum to act as an effective immunoblotting agent following sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Its use in this ELISA indicates that the antiserum recognises the C-terminal region of the protein on the surface of lipoprotein particles. The ELISA had a sensitivity of less than 37 ng/ml and intra- and inter-assay coefficients of variation of 3.8% and 8.6%, respectively. There was no cross-reaction in the ELISA against serum albumin, ovalbumin, thyroglobulin, or apo B-100 (purified by immunoaffinity chromatography), and high lipid concentrations (as Intralipid) did not interfere. A low density lipoprotein fraction reacted in the ELISA but SDS-PAGE-Western blot analysis confirmed the presence, in the fraction, of a small amount of apo B-48, indicating the existence of low density dietary-derived lipoprotein particles. ELISA and SDS-PAGE-Western blot analysis were used to measure apo B-48 in 12 series of postprandial samples collected from 4 diabetic and 8 normal subjects, following test meals of varying fat content. The mean correlation between the two methods was r = 0.74. The mean fasting concentration of apo B-48 in the TRL fractions from 15 healthy men was 0.46 μg/ml of plasma.

The impact of minimum services laws on real estate brokerage competitive intensity

As many as fourteen US states have now mandated minimum service requirements for real estate brokerage relationships in residential transactions. This study attempts to determine whether these minimum service laws have any impact on brokerage competition. Federal government agencies allege such laws discourage competition because they limit the offering of nontraditional brokerage services. However, alternatively, a legislative “bright line” definition of the lowest level of acceptable service may reduce any perceived risk in offering non-traditional brokerage services and therefore encourage competition. Using several empirical strategies and state-level data over nine years (2000-08), we do not find any consistent and significant impact (positive/negative) of minimum services laws on number of licensees per 100 households, our proxy for competition. Interestingly, we also find that association strength, as measured by Realtor association membership penetration, has a strong deterring effect on competition.

Re-conceptualising public participation in spatial planning: a view through autopoiesis

This article examines the relevance of the concept of autopoiesis for public participation in spatial planning. The concept of autopoiesis within social science, as advanced by Niklas Luhmann (1995) argues for a systemic, consistent and sophisticated theory of society based on a systems view, as opposed to more familiar action-based theories (for instance as in the case of the Habermasian tradition). By examining the relevance of the concept for public participation in spatial planning, this article highlights specific aspects of public participation that draw attention to dimensions of planning that are not currently explicitly highlighted within mainstream discourses in planning

The 'algebra as object' analogy: a view from school

Treating algebraic symbols as objects (eg. “‘a’ means ‘apple’”) is a means of introducing elementary simplification of algebra, but causes problems further on. This current school-based research included an examination of texts still in use in the mathematics department, and interviews with mathematics teachers, year 7 pupils and then year 10 pupils asking them how they would explain, “3a + 2a = 5a” to year 7 pupils. Results included the notion that the ‘algebra as object’ analogy can be found in textbooks in current usage, including those recently published. Teachers knew that they were not ‘supposed’ to use the analogy but not always clear why, nevertheless stating methods of teaching consistent with an‘algebra as object’ approach. Year 7 pupils did not explicitly refer to ‘algebra as object’, although some of their responses could be so interpreted. In the main, year 10 pupils used ‘algebra as object’ to explain simplification of algebra, with some complicated attempts to get round the limitations. Further research would look to establish whether the appearance of ‘algebra as object’ in pupils’ thinking between year 7 and 10 is consistent and, if so, where it arises. Implications also are for on-going teacher training with alternatives to introducing such simplification.

The influence of the QBO on the propagation of equatorial waves into the stratosphere

The variation of stratospheric equatorial wave characteristics with the phase of the quasi-biennial oscillation (QBO) is investigated using ECMWF Re-Analysis and NOAA outgoing longwave radiation (OLR) data. The impact of the QBO phases on the upward propagation of equatorial waves is found to be consistent and significant. In the easterly phase, there is larger Kelvin wave amplitude but smaller westward-moving mixed Rossby–gravity (WMRG) and n = 1 Rossby (R1) wave amplitude due to reduced propagation from the upper troposphere into the lower stratosphere, compared with the westerly phase. Differences in the wave amplitude exist in a deeper layer in summer than in winter, consistent with the seasonality of ambient zonal winds. There is a strong evidence of Kelvin wave amplitude peaking just below the descending westerly phase, suggesting that Kelvin waves act to bring the westerly phase downward. However, the corresponding evidence for WMRG and R1 waves is less clear. In the lower stratosphere there is zonal variation in equatorial waves. This reflects the zonal asymmetry of wave amplitudes in the upper troposphere, the source for the lower-stratospheric waves. In easterly winters the upper-tropospheric WMRG and R1 waves over the eastern Pacific region appear to be somewhat stronger compared to climatology, perhaps because of the accumulation of waves that are unable to propagate upward into the lower stratosphere. Vertical propagation features of these waves are generally consistent with theory and suggest a mixture of Doppler shifting by ambient flows and filtering. Some lower-stratosphere equatorial waves have a connection with preceding tropical convection, especially for Kelvin and R1 waves in winter.

A low-order model investigation of the analysis of gravity waves in the ensemble Kalman filter.

The behavior of the ensemble Kalman filter (EnKF) is examined in the context of a model that exhibits a nonlinear chaotic (slow) vortical mode coupled to a linear (fast) gravity wave of a given amplitude and frequency. It is shown that accurate recovery of both modes is enhanced when covariances between fast and slow normal-mode variables (which reflect the slaving relations inherent in balanced dynamics) are modeled correctly. More ensemble members are needed to recover the fast, linear gravity wave than the slow, vortical motion. Although the EnKF tends to diverge in the analysis of the gravity wave, the filter divergence is stable and does not lead to a great loss of accuracy. Consequently, provided the ensemble is large enough and observations are made that reflect both time scales, the EnKF is able to recover both time scales more accurately than optimal interpolation (OI), which uses a static error covariance matrix. For OI it is also found to be problematic to observe the state at a frequency that is a subharmonic of the gravity wave frequency, a problem that is in part overcome by the EnKF.However, error in themodeled gravity wave parameters can be detrimental to the performance of the EnKF and remove its implied advantages, suggesting that a modified algorithm or a method for accounting for model error is needed.

A good enough approach to setting planning obligations

In this paper we propose an alternative model of, what is often called, land value capture in the planning system. Based on development viability models, negotiations and policy formation regarding the level of planning obligations have taken place at the local level with little clear guidance on technique, approach and method. It is argued that current approaches are regressive and fail to reflect how the ability of sites to generate planning gain can vary over time and between sites. The alternative approach suggested here attempts to rationalise rather than replace the existing practice of development viability appraisal. It is based upon the assumption that schemes with similar development values should produce similar levels of return to the landowner, developer and other stakeholders in the development as well as similar levels of planning obligations in all parts of the country. Given the high level of input uncertainty in viability modelling, a simple viability model is ‘good enough’ to quantify the maximum level of planning obligations for a given level of development value. We have argued that such an approach can deliver a more durable, equitable, simpler, consistent and cheaper method for policy formation regarding planning obligations.

A haplotype at the UCP1 gene locus contributes to genetic risk for type 2 diabetes in Asian Indians (CURES-72)

BACKGROUND: The gene encoding for uncoupling protein-1 (UCP1) is considered to be a candidate gene for type 2 diabetes because of its role in thermogenesis and energy expenditure. The objective of the study was to examine whether genetic variations in the UCP1 gene are associated with type 2 diabetes and its related traits in Asian Indians. METHODS: The study subjects, 810 type 2 diabetic subjects and 990 normal glucose tolerant (NGT) subjects, were chosen from the Chennai Urban Rural Epidemiological Study (CURES), an ongoing population-based study in southern India. The polymorphisms were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies. RESULTS: The three polymorphisms, namely -3826A-->G, an A-->C transition in the 5'-untranslated region (UTR) and Met229Leu, were not associated with type 2 diabetes. However, the frequency of the A-C-Met (-3826A-->G-5'UTR A-->C-Met229Leu) haplotype was significantly higher among the type 2 diabetic subjects (2.67%) compared with the NGT subjects (1.45%, P < 0.01). The odds ratio for type 2 diabetes for the individuals carrying the haplotype A-C-Met was 1.82 (95% confidence interval, 1.29-2.78, P = 0.009). CONCLUSIONS: The haplotype, A-C-Met, in the UCP1 gene is significantly associated with the increased genetic risk for developing type 2 diabetes in Asian Indians.

Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population

Peroxisome proliferator-activated receptor-gamma2 (PPARG2) is a nuclear hormone receptor of ligand-dependent transcription factor involved in adipogenesis and a molecular target of the insulin sensitizers thiazolidinediones. We addressed the question of whether the 3 variants (-1279G/A, Pro12Ala, and His478His) in the PPARG2 gene are associated with type 2 diabetes mellitus and its related traits in a South Indian population. The study subjects (1000 type 2 diabetes mellitus and 1000 normal-glucose-tolerant subjects) were chosen randomly from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The variants were screened by single-stranded conformational variant, direct sequencing, and restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. The -1279G/A, Pro12Ala, and His478His variants of the PPARG2 gene were not associated with type 2 diabetes mellitus. However, the 2-loci analyses showed that, in the presence of Pro/Pro genotype of the Pro12Ala variant, the -1279G/A promoter variant showed increased susceptibility to type 2 diabetes mellitus (odds ratio, 2.092; 95% confidence interval, 1.22-3.59; P = .008), whereas in the presence of 12Ala allele, the -1279G/A showed a protective effect against type 2 diabetes mellitus (odds ratio, 0.270; 95% confidence interval, 0.15-0.49; P < .0001). The 3-loci haplotype analysis showed that the A-Ala-T (-1279G/A-Pro12Ala-His478His) haplotype was associated with a reduced risk of type 2 diabetes mellitus (P < .0001). Although our data indicate that the PPARG2 gene variants, independently, have no association with type 2 diabetes mellitus, the 2-loci genotype analysis involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have shown a significant association with type 2 diabetes mellitus in this South Indian population.

Effect of polymorphisms in the PPARGC1A gene on body fat in Asian Indians

OBJECTIVE: To evaluate whether polymorphisms in the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PPARGC1A) gene were related to body fat in Asian Indians. METHODS: Three polymorphisms of PPARGC1A gene, the Thr394Thr, Gly482Ser and +A2962G, were genotyped on 82 type 2 diabetic and 82 normal glucose tolerant (NGT) subjects randomly chosen from the Chennai Urban Rural Epidemiology Study using PCR-RFLP, and the nature of the variants were confirmed using direct sequencing. Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies using an expectation-maximization algorithm. Visceral, subcutaneous and total abdominal fat were measured using computed tomography, whereas dual X-ray absorptiometry was used to measure central abdominal and total body fat. RESULTS: None of the three polymorphisms studied were in LD. The genotype (0.59 vs 0.32, P=0.001) and allele (0.30 vs 0.17, P=0.007) frequencies of Thr394Thr polymorphism were significantly higher in type 2 diabetic subjects compared to those in NGT subjects. The odds ratio for diabetes (adjusted for age, sex and body mass index) for the susceptible genotype, XA (GA+AA) of Thr394Thr polymorphism, was 2.53 (95% confidence intervals: 1.30-5.04, P=0.009). Visceral and subcutaneous fat were significantly higher in NGT subjects with XA genotype of the Thr394Thr polymorphism compared to those with GG genotype (visceral fat: XA 148.2+/-46.9 vs GG 106.5+/-51.9 cm(2), P=0.001; subcutaneous fat: XA 271.8+/-167.1 vs GG 181.5+/-78.5 cm(2), P=0.001). Abdominal (XA 4521.9+/-1749.6 vs GG 3445.2+/-1443.4 g, P=0.004), central abdominal (XA 1689.0+/-524.0 vs GG 1228.5+/-438.7 g, P<0.0001) and non-abdominal fat (XA 18763.8+/-8789.4 vs GG 13160.4+/-4255.3 g, P<0.0001) were also significantly higher in the NGT subjects with XA genotype compared to those with GG genotype. The Gly482Ser and +A2962G polymorphisms were not associated with any of the body fat measures. CONCLUSION: Among Asian Indians, the Thr394Thr (G --> A) polymorphism is associated with increased total, visceral and subcutaneous body fat.

Transreal proof of the existence of universal possible worlds

Transreal arithmetic is total, in the sense that the fundamental operations of addition, subtraction, multiplication and division can be applied to any transreal numbers with the result being a transreal number [1]. In particular division by zero is allowed. It is proved, in [3], that transreal arithmetic is consistent and contains real arithmetic. The entire set of transreal numbers is a total semantics that models all of the semantic values, that is truth values, commonly used in logics, such as the classical, dialetheaic, fuzzy and gap values [2]. By virtue of the totality of transreal arithmetic, these logics can be implemented using total, arithmetical functions, specifically operators, whose domain and counterdomain is the entire set of transreal numbers