Tests of the ratio rule in categorization

Many theories of learning and memory (e.g. connectionist, associative, rational, exemplar-based) produce psychological magnitude terms as output (i.e. numbers representing the momentary level of some subjective property). Many theories assume that these numbers may be translated into choice probabilities via the Ratio Rule, a.k.a. the Choice Axiom (Luce, 1959) or the Constant-Ratio Rule (Clarke, 1957). We present two categorization experiments employing artificial, visual, prototype-structured stimuli constructed from twelve symbols positioned on a grid. The Ratio Rule is shown to be incorrect for these experiments, given the assumption that the magnitude terms for each category are univariate functions of the number of category-appropriate symbols contained in the presented stimulus. A connectionist winner-take-all model of categorical decision (Wills & McLaren, 1997) is shown to account for our data given the same assumption. The central feature underlying the success of this model is the assumption that categorical decisions are based on a Thurstonian choice process (Thurstone, 1927, Case V) whose noise distribution is not double exponential in form

Fluorescence-based incision assay for human XPF-ERCC1 activity identifies important elements of DNA junction recognition

The structure-specific endonuclease activity of the human XPF–ERCC1 complex is essential for a number of DNA processing mechanisms that help to maintain genomic integrity. XPF–ERCC1 cleaves DNA structures such as stem–loops, bubbles or flaps in one strand of a duplex where there is at least one downstream single strand. Here, we define the minimal substrate requirements for cleavage of stem–loop substrates allowing us to develop a real-time fluorescence-based assay to measure endonuclease activity. Using this assay, we show that changes in the sequence of the duplex upstream of the incision site results in up to 100-fold variation in cleavage rate of a stem-loop substrate by XPF-ERCC1. XPF–ERCC1 has a preference for cleaving the phosphodiester bond positioned on the 3′-side of a T or a U, which is flanked by an upstream T or U suggesting that a T/U pocket may exist within the catalytic domain. In addition to an endonuclease domain and tandem helix–hairpin–helix domains, XPF has a divergent and inactive DEAH helicase-like domain (HLD). We show that deletion of HLD eliminates endonuclease activity and demonstrate that purified recombinant XPF–HLD shows a preference for binding stem–loop structures over single strand or duplex alone, suggesting a role for the HLD in initial structure recognition. Together our data describe features of XPF–ERCC1 and an accepted model substrate that are important for recognition and efficient incision activity

HST ultraviolet spectral energy distributions for three ultraluminous infrared galaxies

We present HST Faint Object Camera ultraviolet (230 nm and 140 nm) images of three ultraluminous infrared galaxies (ULIG: L_ir > 10^12 L_sun) selected from the IRAS Revised Bright Galaxy Sample. The purpose is to estimate spectral energy distributions (SEDs) to facilitate the identification of similar objects at high redshift in deep optical, infrared, and submm surveys. All three galaxies (VII Zw031 = IRAS F12112+0305, and IRAS F22491-1808) were well detected at 230 nm. Two of the three were marginally detected at 140 nm. The fluxes, together with ground-based optical and infrared photometry, are used to compute SEDs over a wide wavelength range. The measured SEDs drop from the optical to the ultraviolet, but the magnitude of the drop ranges from a factor of ~3 in IRAS F22491-1808 to a factor of ~100 in VIIZw031. This is most likely due to different internal extinctions. Such an interpretation is also suggested by extrapolating to ultraviolet wavelengths the optical internal extinction measured in VIIZw031. K-corrections are calculated to determine the colors of the sample galaxies as seen at high redshifts. Galaxies like VIIZw031 have very low observed rest-frame UV fluxes which means that such galaxies at high redshift will be extremely red or even missing in optical surveys. On the other hand, galaxies like IRAS F12112+0305 and IRAS F22491-1808, if seen at high redshift, would be sufficiently blue that they would not easily be distinguished from normal field galaxies, and therefore, identified as ULIGs. The implication is then that submillimeter surveys may be the only means of properly identifying the majority of ULIGs at high redshift.Comment: AJ in press, TeX, 23 pages, 7 tab, 17 figs available also (at higher resolution) from http://www.ast.cam.ac.uk~trentham/ufigs.htm

The cosmic gravitational wave background in a cyclic universe

Inflation predicts a primordial gravitational wave spectrum that is slightly ``red,'' i.e., nearly scale-invariant with slowly increasing power at longer wavelengths. In this paper, we compute both the amplitude and spectral form of the primordial tensor spectrum predicted by cyclic/ekpyrotic models. The spectrum is blue and exponentially suppressed compared to inflation on long wavelengths. The strongest observational constraint emerges from the requirement that the energy density in gravitational waves should not exceed around 10 per cent of the energy density at the time of nucleosynthesis.Comment: 4 pages, 3 figuer

Bringing Social Science Into Critical Zone Science:Exploring Smallholder Farmers' Learning Preferences in Chinese Human-Modified Critical Zones

There is a growing global emphasis on sustainable agriculture to reduce human impacts and improve delivery of Sustainable Development Goals (SDGs). With increasing investment in critical zone observatories (CZOs), it becomes important to understand how sustainable agricultural knowledge is produced, shared and used between different groups including farmers, scientists and government. To explore these issues, scientists leading the knowledge exchange (KE) component of a China-UK CZO program studied three farming regions with contrasting geologies and varying economic levels, using a practice-based research method. We demonstrate how additional funding for social science research allowed us to understand how farmers access and share farming knowledge through bonding, bridging and linking networks, and how this varies spatially, using interviews and survey questionnaires. Knowledge flows, barriers and opportunities for designing locally suited two-way KE activities were identified. First, we highlight the need for a more locally, socially embedded and reflexive approach to build trust and better address pressing local environmental challenges. Second, we show how social science can usefully inform KE for collaborative, international development science, to draw on local knowledge, promote research impacts and capacity building while avoiding knowledge mismatches. Lastly, a blueprint for the design and funding of future CZOs, social-ecological and planetary health research agendas that combine science, social science, local knowledge and KE is presented, including the need for substantive social science research to take place in addition to science research in human-modified landscapes—enabling the CZ science to be better grounded in, informed by and useful to local communities

Blood glucose self-monitoring in type 2 diabetes: a randomised controlled trial

OBJECTIVES: To determine whether self-monitoring of blood glucose (SMBG), either alone or with additional instruction in incorporating the results into self-care, is more effective than usual care in improving glycaemic control in non-insulin-treated diabetes. DESIGN: An open, parallel group randomised controlled trial. SETTING: 24 general practices in Oxfordshire and 24 in South Yorkshire, UK. PARTICIPANTS: Patients with non-insulin-treated type 2 diabetes, aged > or = 25 years and with glycosylated haemoglobin (HbA1c) > or = 6.2%. INTERVENTIONS: A total of 453 patients were individually randomised to one of: (1) standardised usual care with 3-monthly HbA1c (control, n = 152); (2) blood glucose self-testing with patient training focused on clinician interpretation of results in addition to usual care (less intensive self-monitoring, n = 150); (3) SMBG with additional training of patients in interpretation and application of the results to enhance motivation and maintain adherence to a healthy lifestyle (more intensive self-monitoring, n = 151). MAIN OUTCOME MEASURES: The primary outcome was HBA1c at 12 months, and an intention-to-treat analysis, including all patients, was undertaken. Blood pressure, lipids, episodes of hypoglycaemia and quality of life, measured with the EuroQol 5 dimensions (EQ-5D), were secondary measures. An economic analysis was also carried out, and questionnaires were used to measure well-being, beliefs about use of SMBG and self-reports of medication taking, dietary and physical activities, and health-care resource use. RESULTS: The differences in 12-month HbA1c between the three groups (adjusted for baseline HbA1c) were not statistically significant (p = 0.12). The difference in unadjusted mean change in HbA1c from baseline to 12 months between the control and less intensive self-monitoring groups was -0.14% [95% confidence interval (CI) -0.35 to 0.07] and between the control and more intensive self-monitoring groups was -0.17% (95% CI -0.37 to 0.03). There was no evidence of a significantly different impact of self-monitoring on glycaemic control when comparing subgroups of patients defined by duration of diabetes, therapy, diabetes-related complications and EQ-5D score. The economic analysis suggested that SMBG resulted in extra health-care costs and was unlikely to be cost-effective if used routinely. There appeared to be an initial negative impact of SMBG on quality of life measured on the EQ-5D, and the potential additional lifetime gains in quality-adjusted life-years, resulting from the lower levels of risk factors achieved at the end of trial follow-up, were outweighed by these initial impacts for both SMBG groups compared with control. Some patients felt that SMBG was helpful, and there was evidence that those using more intensive self-monitoring perceived diabetes as having more serious consequences. Patients using SMBG were often not clear about the relationship between their behaviour and the test results. CONCLUSIONS: While the data do not exclude the possibility of a clinically important benefit for specific subgroups of patients in initiating good glycaemic control, SMBG by non-insulin-treated patients, with or without instruction in incorporating findings into self-care, did not lead to a significant improvement in glycaemic control compared with usual care monitored by HbA1c levels. There was no convincing evidence to support a recommendation for routine self-monitoring of all patients and no evidence of improved glycaemic control in predefined subgroups of patients

Energy metabolism in mobile, wild-sampled sharks inferred by plasma lipids

Evaluating how predators metabolize energy is increasingly useful for conservation physiology, as it can provide information on their current nutritional condition. However, obtaining metabolic information from mobile marine predators is inherently challenging owing to their relative rarity, cryptic nature and often wide-ranging underwater movements. Here, we investigate aspects of energy metabolism in four free-ranging shark species (n = 281; blacktip, bull, nurse, and tiger) by measuring three metabolic parameters [plasma triglycerides (TAG), free fatty acids (FFA) and cholesterol (CHOL)] via non-lethal biopsy sampling. Plasma TAG, FFA and total CHOL concentrations (in millimoles per litre) varied inter-specifically and with season, year, and shark length varied within a species. The TAG were highest in the plasma of less active

Phosphate steering by Flap Endonuclease 1 promotes 5´-flap specificity and incision to prevent genome instability

DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 50-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 50-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 50polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via ‘phosphate steering’, basic residues energetically steer an inverted ss 50-flap through a gateway over FEN1’s active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA)n repeat expansions in vivo, implying failed phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replication. Thus, phosphate steering is an unappreciated FEN1 function that enforces 50-flap specificity and catalysis, preventing genomic instability

Phosphate steering by Flap Endonuclease 1 promotes 5´-flap specificity and incision to prevent genome instability

DNA replication and repair enzyme Flap Endonuclease 1 (FEN1) is vital for genome integrity, and FEN1 mutations arise in multiple cancers. FEN1 precisely cleaves single-stranded (ss) 50-flaps one nucleotide into duplex (ds) DNA. Yet, how FEN1 selects for but does not incise the ss 50-flap was enigmatic. Here we combine crystallographic, biochemical and genetic analyses to show that two dsDNA binding sites set the 50polarity and to reveal unexpected control of the DNA phosphodiester backbone by electrostatic interactions. Via ‘phosphate steering’, basic residues energetically steer an inverted ss 50-flap through a gateway over FEN1’s active site and shift dsDNA for catalysis. Mutations of these residues cause an 18,000-fold reduction in catalytic rate in vitro and large-scale trinucleotide (GAA)n repeat expansions in vivo, implying failed phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replication. Thus, phosphate steering is an unappreciated FEN1 function that enforces 50-flap specificity and catalysis, preventing genomic instability