Metabolic signatures of human Alzheimer's disease (AD): H-1 NMR analysis of the polar metabolome of post-mortem brain tissue

Brain tissue from so-called Alzheimer's disease (AD) mouse models has previously been examined using H-1 NMR-metabolomics, but comparable information concerning human AD is negligible. Since no animal model recapitulates all the features of human AD we undertook the first H-1 NMR-metabolomics investigation of human AD brain tissue. Human post-mortem tissue from 15 AD subjects and 15 age-matched controls was prepared for analysis through a series of lyophilised, milling, extraction and randomisation steps and samples were analysed using H-1 NMR. Using partial least squares discriminant analysis, a model was built using data obtained from brain extracts. Analysis of brain extracts led to the elucidation of 24 metabolites. Significant elevations in brain alanine (15.4 %) and taurine (18.9 %) were observed in AD patients (p ≤ 0.05). Pathway topology analysis implicated either dysregulation of taurine and hypotaurine metabolism or alanine, aspartate and glutamate metabolism. Furthermore, screening of metabolites for AD biomarkers demonstrated that individual metabolites weakly discriminated cases of AD [receiver operating characteristic (ROC) AUC <0.67; p < 0.05]. However, paired metabolites ratios (e.g. alanine/carnitine) were more powerful discriminating tools (ROC AUC = 0.76; p < 0.01). This study further demonstrates the potential of metabolomics for elucidating the underlying biochemistry and to help identify AD in patients attending the memory clinic

Metabolic signatures of Huntington's disease (HD): 1H NMR analysis of the polar metabolome in post mortem human brain

Huntington’s disease (HD) is an autosomal neurodegenerative disorder affecting approximately 5-10 persons per 100,000 worldwide. The pathophysiology of HD is not fully understood but the age of onset is known to be highly dependent on the number of CAG triplet repeats in the huntingtin gene. Using 1H NMR spectroscopy this study biochemically profiled 39 brain metabolites in post-mortem striatum (n=14) and frontal lobe (n=14) from HD sufferers and controls (n=28). Striatum metabolites were more perturbed with 15 significantly affected in HD cases, compared with only 4 in frontal lobe (P<0.05; q<0.3). The metabolite which changed most overall was urea which decreased 3.25-fold in striatum (P<0.01). Four metabolites were consistently affected in both brain regions. These included the neurotransmitter precursors tyrosine and L-phenylalanine which were significantly depleted by 1.55-1.58-fold and 1.48-1.54-fold in striatum and frontal lobe, respectively (P=0.02-0.03). They also included L-leucine which was reduced 1.54-1.69-fold (P=0.04-0.09) and myo-inositol which was increased 1.26-1.37-fold (P<0.01). Logistic regression analyses performed with MetaboAnalyst demonstrated that data obtained from striatum produced models which were profoundly more sensitive and specific than those produced from frontal lobe. The brain metabolite changes uncovered in this first 1H NMR investigation of human HD offer new insights into the disease pathophysiology. Further investigations of striatal metabolite disturbances are clearly warranted.

Deciding between accounts of the selection task: A reply to Oaksford (2002)

In this paper we report on our attempts to fit the optimal data selection (ODS) model (Oaksford Chater, 1994; Oaksford, Chater, & Larkin, 2000) to the selection task data reported in Feeney and Handley (2000) and Handley, Feeney, and Harper (2002). Although Oaksford (2002b) reports good fits to the data described in Feeney and Handley (2000), the model does not adequately capture the data described in Handley et al. (2002). Furthermore, across all six of the experiments modelled here, the ODS model does not predict participants' behaviour at the level of selection rates for individual cards. Finally, when people's probability estimates are used in the modelling exercise, the model adequately captures only I out of 18 conditions described in Handley et al. We discuss the implications of these results for models of the selection task and claim that they support deductive, rather than probabilistic, accounts of the task.

Alternative antecedents, probabilities, and the suppression of fallacies in Wason's selection task

Three experiments examined the influence of a second rule on the pattern of card selections on Wason's selection task. In Experiment 1 participants received a version of the task with a single test rule or one of two versions of the task with the same original test rule together with a second rule. The probability of q was manipulated in the two-rules conditions by varying the size of the antecedent set in the second rule. The results showed a significant suppression of q card and not-p card selections in the alternative-rule conditions, but no difference as a function of antecedent set size. In Experiment 2 the size of the antecendent set in the two-rules conditions was manipulated using the context of a computer printing double-sided cards. The results showed a significant reduction of q card selections in the two-rules conditions, but no effect of p set size. In Experiment 3 the scenario accompanying the rule was manipulated, and it specified a single alternative antecedent or a number of alternative antecedents. The q card selection rates were not affected by the scenario manipulation but again were suppressed by the presence of a second rule. Our results suggest that people make inferences about the unseen side of the cards when engaging with the task and that these inferences are systematically influenced by the presence of a second rule, but are not influenced by the probabilistic characteristics of this rule. These findings are discussed in the context of decision theoretic views of selection task performance (Oaksford Chater, 1994).

Selection Power and Selection Labor for Information Retrieval

This study examines the relation between selection power and selection labor for information retrieval (IR). It is the first part of the development of a labor theoretic approach to IR. Existing models for evaluation of IR systems are reviewed and the distinction of operational from experimental systems partly dissolved. The often covert, but powerful, influence from technology on practice and theory is rendered explicit. Selection power is understood as the human ability to make informed choices between objects or representations of objects and is adopted as the primary value for IR. Selection power is conceived as a property of human consciousness, which can be assisted or frustrated by system design. The concept of selection power is further elucidated, and its value supported, by an example of the discrimination enabled by index descriptions, the discovery of analogous concepts in partly independent scholarly and wider public discourses, and its embodiment in the design and use of systems. Selection power is regarded as produced by selection labor, with the nature of that labor changing with different historical conditions and concurrent information technologies. Selection labor can itself be decomposed into description and search labor. Selection labor and its decomposition into description and search labor will be treated in a subsequent article, in a further development of a labor theoretic approach to information retrieval.

Quantitative genetics of preference and performance on chickpeas in the noctuid moth, Helicoverpa armigera

If a novel, resistant host-plant genotype arises in the environment, insect populations utilising that host must be able to overcome that resistance in order that they can maintain their ability to feed on that host. The ability to evolve resistance to host-plant defences depends upon additive genetic variation in larval performance and adult host-choice preference. To investigate the potential of a generalist herbivore to respond to a novel resistant host, we estimated the heritability of larval performance in the noctuid moth, Helicoverpa armigera, on a resistant and a susceptible variety of the chickpea, Cicer arietinum, at two different life stages. Heritability estimates were higher for neonates than for third-instar larvae, suggesting that their ability to establish on plants could be key to the evolution of resistance in this species; however, further information regarding the nature of selection in the field would be required to confirm this prediction. There was no genetic correlation between larval performance and oviposition preference, indicating that female moths do not choose the most suitable plant for their offspring. We also found significant genotype by environment interactions for neonates (but not third-instar larvae), suggesting that the larval response to different plant genotypes is stage-specific in this species.

Comparison of passive millimeter-wave and IR imagery in a nautical environment

Results are presented from a trial in which a real-time passive millimetre-wave camera was mounted on a landing craft. The vessel was operated on rivers in the UK, and imagery of surrounding terrain, structures, obstacles and other vessels was obtained. An IR camera was also used, and the differences in signatures of various features are discussed. Opportunities for image fusion are highlighted.

Carbon Isotopic Fractionation of CFCs during Abiotic and Biotic Degradation

Carbon stable isotope ((13)C) fractionation in chlorofluorocarbon (CFC) compounds arising from abiotic (chemical) degradation using zero-valent iron (ZVI) and biotic (landfill gas attenuation) processes is investigated. Batch tests (at 25 °C) for CFC-113 and CFC-11 using ZVI show quantitative degradation of CFC-113 to HCFC-123a and CFC-1113 following pseudo-first-order kinetics corresponding to a half-life (t(1/2)) of 20.5 h, and a ZVI surface-area normalized rate constant (k(SA)) of -(9.8 ± 0.5) × 10(-5) L m(-2) h(-1). CFC-11 degraded to trace HCFC-21 and HCFC-31 following pseudo-first-order kinetics corresponding to t(1/2) = 17.3 h and k(SA) = -(1.2 ± 0.5) × 10(-4) L m(-2) h(-1). Significant kinetic isotope effects of e(‰) = -5.0 ± 0.3 (CFC-113) and -17.8 ± 4.8 (CFC-11) were observed. Compound-specific carbon isotope analyses also have been used here to characterize source signatures of CFC gases (HCFC-22, CFC-12, HFC-134a, HCFC-142b, CFC-114, CFC-11, CFC-113) for urban (UAA), rural/remote (RAA), and landfill (LAA) ambient air samples, as well as in situ surface flux chamber (FLUX; NO FLUX) and landfill gas (LFG) samples at the Dargan Road site, Northern Ireland. The latter values reflect biotic degradation and isotopic fractionation in LFG production, and local atmospheric impact of landfill emissions through the cover. Isotopic fractionations of ?(13)C ~ -13‰ (HCFC-22), ?(13)C ~ -35‰ (CFC-12) and ?(13)C ~ -15‰ (CFC-11) were observed for LFG in comparison to characteristic solvent source signatures, with the magnitude of the isotopic effect for CFC-11 apparently similar to the kinetic isotope effect for (abiotic) ZVI degradation.

Observations of Sausage Modes in Magnetic Pores

We present here evidence for the observation of the magnetohydrodynamic (MHD) sausage modes in magnetic pores in the solar photosphere. Further evidence for the omnipresent nature of acoustic global modes is also found. The empirical decomposition method of wave analysis is used to identify the oscillations detected through a 4170 Å "blue continuum" filter observed with the Rapid Oscillations in the Solar Atmosphere (ROSA) instrument. Out of phase, periodic behavior in pore size and intensity is used as an indicator of the presence of magnetoacoustic sausage oscillations. Multiple signatures of the magnetoacoustic sausage mode are found in a number of pores. The periods range from as short as 30 s up to 450 s. A number of the magnetoacoustic sausage mode oscillations found have periods of 3 and 5 minutes, similar to the acoustic global modes of the solar interior. It is proposed that these global oscillations could be the driver of the sausage-type magnetoacoustic MHD wave modes in pores.

Degradation of carbon disulphide (CS2) in soils and groundwater from a CS2 -contaminated site

This study is the first investigation of biodegradation of carbon disulphide (CS₂) in soil that provides estimates of degradation rates and identifies intermediate degradation products and carbon isotope signatures of degradation. Microcosm studies were undertaken under anaerobic conditions using soil and groundwater recovered from CS₂-contaminated sites. Proposed degradation mechanisms were validated using equilibrium speciation modelling of concentrations and carbon isotope ratios. A first-order degradation rate constant of 1.25 × 10-2 h-1 was obtained for biological degradation with soil. Carbonyl sulphide (COS) and hydrogen sulphide (H₂S) were found to be intermediates of degradation, but did not accumulate in vials. A 13C/12C enrichment factor of -7.5 ± 0.8 ‰ was obtained for degradation within microcosms with both soil and groundwater whereas a 13C/12C enrichment factor of -23.0 ± 2.1 ‰ was obtained for degradation with site groundwater alone. It can be concluded that biological degradation of both CS2-contaminated soil and groundwater is likely to occur in the field suggesting that natural attenuation may be an appropriate remedial tool at some sites. The presence of biodegradation by-products including COS and H₂S indicates that biodegradation of CS₂ is occurring and stable carbon isotopes are a promising tool to quantify CS₂ degradation.

Transcriptional responses of Burkholderia cenocepacia to polymyxin B in isogenic strains with diverse polymyxin B resistance phenotypes

Background: Burkholderia cenocepacia is a Gram-negative opportunistic pathogen displaying high resistance to antimicrobial peptides and polymyxins. We identified mechanisms of resistance by analyzing transcriptional changes to polymyxin B treatment in three isogenic B. cenocepacia strains with diverse polymyxin B resistance phenotypes: the polymyxin B-resistant parental strain K56-2, a polymyxin B-sensitive K56-2 mutant strain with heptoseless lipopolysaccharide (LPS) (RSF34), and a derivative of RSF34 (RSF34 4000B) isolated through multiple rounds of selection in polymyxin B that despite having a heptoseless LPS is highly polymyxin B-resistant.

Urban housing and the role of 'underclass' processes: the case of Ireland

Rising levels of urban deprivation and a perception that poverty has become more concentrated in such areas and has taken on a qualitatively different character have provoked a variety of popular and academic responses. The potentially most fruitful set of hypotheses focuses on the unintended of weak labour force attachment and social isolation is perceived to lead to behaviour and orientations that contribute to a vicious circle of deprivation. In examining the value of this conceptual framework in the Irish case we proceed by measuring directly the social-psychological factors which ave hypothesized to mediate the 'underclass' process.

A significantly higher level of poverty is found in urban public-sector tenant households. This finding cannot be accounted for entirely by socio-demographic differences. It is the assessment of this net or residual effect that is crucial to an evaluation of vicious circle explanations. Controlling for the critical social-psychological factors we found that net effect was reduced by less than a quarter and concluded that the remaining effect is more plausibly attributed to the role of selection than to underclass processes. Analysis of the changing relationship between urban public-sector tenancy and poverty provides support for this interpretation.

For the main part the distinctiveness of social housing tenants is a consequence of the disadvantages they stiffer in relation to employment opportunities and living standards. Ultimately it is these problems that policy interventions, whatever the level at which they take place, must address.

2D simulations of the double-detonation model for thermonuclear transients from low-mass carbon-oxygen white dwarfs

Thermonuclear explosions may arise in binary star systems in which a carbon-oxygen (CO) white dwarf (WD) accretes helium-rich material from a companion star. If the accretion rate allows a sufficiently large mass of helium to accumulate prior to ignition of nuclear burning, the helium surface layer may detonate, giving rise to an astrophysical transient. Detonation of the accreted helium layer generates shock waves that propagate into the underlying CO WD. This might directly ignite a detonation of the CO WD at its surface (an edge-lit secondary detonation) or compress the core of the WD sufficiently to trigger a CO detonation near the centre. If either of these ignition mechanisms works, the two detonations (helium and CO) can then release sufficient energy to completely unbind the WD. These 'double-detonation' scenarios for thermonuclear explosion of WDs have previously been investigated as a potential channel for the production of Type Ia supernovae from WDs of ~ 1 M . Here we extend our 2D studies of the double-detonation model to significantly less massive CO WDs, the explosion of which could produce fainter, more rapidly evolving transients. We investigate the feasibility of triggering a secondary core detonation by shock convergence in low-mass CO WDs and the observable consequences of such a detonation. Our results suggest that core detonation is probable, even for the lowest CO core masses that are likely to be realized in nature. To quantify the observable signatures of core detonation, we compute spectra and light curves for models in which either an edge-lit or compression-triggered CO detonation is assumed to occur. We compare these to synthetic observables for models in which no CO detonation was allowed to occur. If significant shock compression of the CO WD occurs prior to detonation, explosion of the CO WD can produce a sufficiently large mass of radioactive iron-group nuclei to significantly affect the light curves. In particular, this can lead to relatively slow post-maximum decline. If the secondary detonation is edge-lit, however, the CO WD explosion primarily yields intermediate-mass elements that affect the observables more subtly. In this case, near-infrared observations and detailed spectroscopic analysis would be needed to determine whether a core detonation occurred. We comment on the implications of our results for understanding peculiar astrophysical transients including SN 2002bj, SN 2010X and SN 2005E. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.