Evidence that interaction between conserved residues in transmembrane helices 2, 3, and 7 are crucial for human VPAC1 receptor activation

The VPAC(1) receptor belongs to family B of G protein-coupled receptors (GPCR-B) and is activated upon binding of the vasoactive intestinal peptide (VIP). Despite the recent determination of the structure of the N terminus of several members of this receptor family, little is known about the structure of the transmembrane (TM) region and about the molecular mechanisms leading to activation. In the present study, we designed a new structural model of the TM domain and combined it with experimental mutagenesis experiments to investigate the interaction network that governs ligand binding and receptor activation. Our results suggest that this network involves the cluster of residues Arg(188) in TM2, Gln(380) in TM7, and Asn(229) in TM3. This cluster is expected to be altered upon VIP binding, because Arg(188) has been shown previously to interact with Asp(3) of VIP. Several point mutations at positions 188, 229, and 380 were experimentally characterized and were shown to severely affect VIP binding and/or VIP-mediated cAMP production. Double mutants built from reciprocal residue exchanges exhibit strong cooperative or anticooperative effects, thereby indicating the spatial proximity of residues Arg(188), Gln(380), and Asn(229). Because these residues are highly conserved in the GPCR-B family, they can moreover be expected to have a general role in mediating function.

Evidence of a transition from perceptual to category induction in 3- to 9-year-old children

We examined whether inductive reasoning development is better characterized by accounts assuming an early category bias versus an early perceptual bias. We trained 264 children aged 3 to 9 years to categorize novel insects using a rule that directly pitted category membership against appearance. This was followed by an induction task with perceptual distractors at different levels of featural similarity. An additional 52 children were given the same training followed by an induction task with alternative stimuli. Categorization performance was consistently high, however we found a gradual transition from a perceptual bias in our youngest children to a category bias around age 6-7. In addition, children of all ages were equally distracted by higher levels of featural similarity. The transition is unlikely to be due to an increased ability to inhibit perceptual distractors. Instead, we argue that the transition is driven by a fundamental change in children’s understanding of category membership.

Theory and data for area summation of contrast with and without uncertainty:evidence for a noisy energy model

Contrast sensitivity improves with the area of a sine-wave grating, but why? Here we assess this phenomenon against contemporary models involving spatial summation, probability summation, uncertainty, and stochastic noise. Using a two-interval forced-choice procedure we measured contrast sensitivity for circular patches of sine-wave gratings with various diameters that were blocked or interleaved across trials to produce low and high extrinsic uncertainty, respectively. Summation curves were steep initially, becoming shallower thereafter. For the smaller stimuli, sensitivity was slightly worse for the interleaved design than for the blocked design. Neither area nor blocking affected the slope of the psychometric function. We derived model predictions for noisy mechanisms and extrinsic uncertainty that was either low or high. The contrast transducer was either linear (c1.0) or nonlinear (c2.0), and pooling was either linear or a MAX operation. There was either no intrinsic uncertainty, or it was fixed or proportional to stimulus size. Of these 10 canonical models, only the nonlinear transducer with linear pooling (the noisy energy model) described the main forms of the data for both experimental designs. We also show how a cross-correlator can be modified to fit our results and provide a contemporary presentation of the relation between summation and the slope of the psychometric function.

Tacit collusion, firm asymmetries and numbers:evidence from EC merger cases

This paper estimates the implicit model, especially the roles of size asymmetries and firm numbers, used by the European Commission to identify mergers with coordinated effects. This subset of cases offers an opportunity to shed empirical light on the conditions where a Competition Authority believes tacit collusion is most likely to arise. We find that, for the Commission, tacit collusion is a rare phenomenon, largely confined to markets of two, more or less symmetric, players. This is consistent with recent experimental literature, but contrasts with the facts on ‘hard-core’ collusion in which firm numbers and asymmetries are often much larger.

Tacit vs. overt collusion firm asymmetries and numbers:what's the evidence?

It is conventional wisdom that collusion is more likely the fewer firms there are in a market and the more symmetric they are. This is often theoretically justified in terms of a repeated non-cooperative game. Although that model fits more easily with tacit than overt collusion, the impression sometimes given is that ‘one model fits all’. Moreover, the empirical literature offers few stylized facts on the most simple of questions—how few are few and how symmetric is symmetric? This paper attempts to fill this gap while also exploring the interface of tacit and overt collusion, albeit in an indirect way. First, it identifies the empirical model of tacit collusion that the European Commission appears to have employed in coordinated effects merger cases—apparently only fairly symmetric duopolies fit the bill. Second, it shows that, intriguingly, the same story emerges from the quite different experimental literature on tacit collusion. This offers a stark contrast with the findings for a sample of prosecuted cartels; on average, these involve six members (often more) and size asymmetries among members are often considerable. The indirect nature of this ‘evidence’ cautions against definitive conclusions; nevertheless, the contrast offers little comfort for those who believe that the same model does, more or less, fit all.

Astrocytic GABA transporter GAT-1 dysfunction in experimental absence seizures

An enhanced tonic GABA-A inhibition in the thalamus plays a crucial role in experimental absence seizures, and has been attributed, on the basis of indirect evidence, to a dysfunction of the astrocytic GABA transporter-1 (GAT-1). Here, the GABA transporter current was directly investigated in thalamic astrocytes from a well-established genetic model of absence seizures, the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), and its non-epileptic control (NEC) strain. We also characterized the novel form of GABAergic and glutamatergic astrocyte-to-neuron signalling by recording slow outward currents (SOCs) and slow inward currents (SICs), respectively, in thalamocortical (TC) neurons of both strains. In patch-clamped astrocytes, the GABA transporter current was abolished by combined application of the selective GAT-1 and GAT-3 blocker, NO711 (30µM) and SNAP5114 (60µM), respectively, to GAERS and NEC thalamic slices. NO711 alone significantly reduced (41%) the transporter current in NEC, but had no effect in GAERS. SNAP5114 alone reduced by half the GABA transporter current in NEC, whilst it abolished it in GAERS. SIC properties did not differ between GAERS and NEC TC neurons, whilst moderate changes in SOC amplitude and kinetics were observed. These data provide the first direct demonstration of a malfunction of the astrocytic thalamic GAT-1 transporter in absence epilepsy and support an abnormal astrocytic modulation of thalamic ambient GABA levels. Moreover, while the glutamatergic astrocyte-neuron signalling is unaltered in the GAERS thalamus, the changes in some properties of the GABAergic astrocyte-neuron signaling in this epileptic strain may contribute to the generation of absence seizures.

Formant-Frequency Variation and Informational Masking of Speech by Extraneous Formants : Evidence Against Dynamic and Speech-Specific Acoustical Constraints

How speech is separated perceptually from other speech remains poorly understood. Recent research indicates that the ability of an extraneous formant to impair intelligibility depends on the variation of its frequency contour. This study explored the effects of manipulating the depth and pattern of that variation. Three formants (F1+F2+F3) constituting synthetic analogues of natural sentences were distributed across the 2 ears, together with a competitor for F2 (F2C) that listeners must reject to optimize recognition (left = F1+F2C; right = F2+F3). The frequency contours of F1 − F3 were each scaled to 50% of their natural depth, with little effect on intelligibility. Competitors were created either by inverting the frequency contour of F2 about its geometric mean (a plausibly speech-like pattern) or using a regular and arbitrary frequency contour (triangle wave, not plausibly speech-like) matched to the average rate and depth of variation for the inverted F2C. Adding a competitor typically reduced intelligibility; this reduction depended on the depth of F2C variation, being greatest for 100%-depth, intermediate for 50%-depth, and least for 0%-depth (constant) F2Cs. This suggests that competitor impact depends on overall depth of frequency variation, not depth relative to that for the target formants. The absence of tuning (i.e., no minimum in intelligibility for the 50% case) suggests that the ability to reject an extraneous formant does not depend on similarity in the depth of formant-frequency variation. Furthermore, triangle-wave competitors were as effective as their more speech-like counterparts, suggesting that the selection of formants from the ensemble also does not depend on speech-specific constraints.

Formant-frequency variation and informational masking of speech by extraneous formants:evidence against dynamic and speech-specific acoustical constraints

How speech is separated perceptually from other speech remains poorly understood. Recent research indicates that the ability of an extraneous formant to impair intelligibility depends on the variation of its frequency contour. This study explored the effects of manipulating the depth and pattern of that variation. Three formants (F1+F2+F3) constituting synthetic analogues of natural sentences were distributed across the 2 ears, together with a competitor for F2 (F2C) that listeners must reject to optimize recognition (left = F1+F2C; right = F2+F3). The frequency contours of F1 - F3 were each scaled to 50% of their natural depth, with little effect on intelligibility. Competitors were created either by inverting the frequency contour of F2 about its geometric mean (a plausibly speech-like pattern) or using a regular and arbitrary frequency contour (triangle wave, not plausibly speech-like) matched to the average rate and depth of variation for the inverted F2C. Adding a competitor typically reduced intelligibility; this reduction depended on the depth of F2C variation, being greatest for 100%-depth, intermediate for 50%-depth, and least for 0%-depth (constant) F2Cs. This suggests that competitor impact depends on overall depth of frequency variation, not depth relative to that for the target formants. The absence of tuning (i.e., no minimum in intelligibility for the 50% case) suggests that the ability to reject an extraneous formant does not depend on similarity in the depth of formant-frequency variation. Furthermore, triangle-wave competitors were as effective as their more speech-like counterparts, suggesting that the selection of formants from the ensemble also does not depend on speech-specific constraints. © 2014 The Author(s).

Sympathetic control of accommodation:evidence for inter-subject variation

Autonomic innervation of ciliary smooth muscle is mediated principally by the parasympathetic nervous system and is supplemented by the sympathetic nervous system. Previous drug and nerve stimulation experiments on humans and animals have demonstrated that sympathetic innervation is inhibitory (via β-2 adrenoceptors), relatively small, slow and augmented by concurrent levels of background parasympathetic activity. These characteristics are pertinent to the sympathetic system having a specific role in our ability to adapt successfully to sustained near vision tasks and, given the clear association between near vision and the onset and development of myopia, to a putative aetiological role in myopia development in pre-disposed individuals. A fifth characteristic, namely the variation between individuals in access to an inhibitory sympathetic facility is therefore of particular interest. A novel method for continuous recording of accommodation, currently employed in a large sample longitudinal study of myopia in young adults, was used following topical instillation of non-selective (timolol) and selective (betaxolol) sympathetic β-adrenoceptor antagonists. Measures of post-task accommodative hysteresis were taken with reference to the time-course of regression of accommodation when open-loop (Difference of Gaussian) conditions were immediately imposed following short (10 s) and long (3 min) duration far (0D) and near (3D above tonic level) tasks viewed through a Badal system. Data confirm earlier informal experimental observations that only one in three individuals are likely to have access to a sympathetic inhibitory facility during sustained near vision. © 2002 The College of Optometrists.

Exploiting heterogeneous scientific literature networks to combat ranking bias:evidence from the computational linguistics area

It is important to help researchers find valuable papers from a large literature collection. To this end, many graph-based ranking algorithms have been proposed. However, most of these algorithms suffer from the problem of ranking bias. Ranking bias hurts the usefulness of a ranking algorithm because it returns a ranking list with an undesirable time distribution. This paper is a focused study on how to alleviate ranking bias by leveraging the heterogeneous network structure of the literature collection. We propose a new graph-based ranking algorithm, MutualRank, that integrates mutual reinforcement relationships among networks of papers, researchers, and venues to achieve a more synthetic, accurate, and less-biased ranking than previous methods. MutualRank provides a unified model that involves both intra- and inter-network information for ranking papers, researchers, and venues simultaneously. We use the ACL Anthology Network as the benchmark data set and construct the gold standard from computer linguistics course websites of well-known universities and two well-known textbooks. The experimental results show that MutualRank greatly outperforms the state-of-the-art competitors, including PageRank, HITS, CoRank, Future Rank, and P-Rank, in ranking papers in both improving ranking effectiveness and alleviating ranking bias. Rankings of researchers and venues by MutualRank are also quite reasonable.

Juror need for cognition and sensitivity to methodological flaws in expert evidence

Two studies investigated the influence of juror need for cognition on the systematic and heuristic processing of expert evidence. U.S. citizens reporting for jury duty in South Florida read a 15-page summary of a hostile work environment case containing expert testimony. The expert described a study she had conducted on the effects of viewing sexualized materials on men's behavior toward women. Certain methodological features of the expert's research varied across experimental conditions. In Study 1 (N = 252), the expert's study was valid, contained a confound, or included the potential for experimenter bias (internal validity) and relied on a small or large sample (sample size) of college undergraduates or trucking employees (ecological validity). When the expert's study included trucking employees, high need for cognition jurors in Study 1 rated the expert more credible and trustworthy than did low need for cognition jurors. Jurors were insensitive to variations in the study's internal validity or sample size. Juror ratings of plaintiff credibility, plaintiff trustworthiness, and study quality were positively correlated with verdict. In Study 2 (N = 162), the expert's published or unpublished study (general acceptance) was either valid or lacked an appropriate control group (internal validity) and included a sample of college undergraduates or trucking employees (ecological validity). High need for cognition jurors in Study 2 found the defendant liable more often and evaluated the expert evidence more favorably when the expert's study was internally valid than when an appropriate control group was missing. Low need for cognition jurors did not differentiate between the internally valid and invalid study. Variations in the study's general acceptance and ecological validity did not affect juror judgments. Juror ratings of expert and plaintiff credibility, plaintiff trustworthiness, and study quality were positively correlated with verdict. The present research demonstrated that the need for cognition moderates juror sensitivity to expert evidence quality and that certain message-related heuristics influence juror judgments when ability or motivation to process systematically is low. ^

True and false confessions to an intentional act: A novel experimental paradigm

Due to the powerful nature of confession evidence, it is imperative that we investigate the factors that affect the likelihood of obtaining true and false confessions. Previous research has been conducted with a paradigm limited to the study of false confessions to an act of negligence, thereby limiting the generalizability of the findings. The first goal of the current study was to introduce a novel paradigm involving a more serious, intentional act that can be used in the study of both true and false confessions. The second goal was to explore the effects of two police interrogation tactics, minimization and an offer of leniency, on true and false confession rates. ^ Three hundred and thirty-four undergraduates at a large southeastern university were recruited to participate in a study on problem-solving and decision-making. During the course of the laboratory experiment, participants were induced to intentionally break or not break an experimental rule, an act that was characterized as “cheating.” All participants (i.e., both innocent and guilty) were later accused of the act and interrogated. For half of the participants, the interrogator used minimization tactics, which involved downplaying the seriousness of the offense, expressing sympathy, and providing face-saving excuses, in order to encourage the participant to confess. An offer of leniency was also manipulated in which half the participants were offered a “deal” that involved the option of confessing and accepting a known punishment or not confessing and facing the threat of harsher punishment. Results indicated that guilty persons were more likely to confess than innocent persons, and that the use of minimization and an explicit offer of leniency increased both the true and false confession rates. Furthermore, a cumulative effect of techniques was observed, such that the diagnosticity of the interrogation (the ratio of true confessions to false confessions) decreased as the number of techniques used increased. Taken together, the results suggest that caution should be used when implementing these techniques in the interrogation room. ^

Jury decision making and the Story Model: How do deliberation style and evidence order influence the story that juries create?

This study investigated the utility of the Story Model for decision making at the jury level by examining the influence of evidence order and deliberation style on story consistency and guilt. Participants were shown a video-taped trial stimulus and then provided case perceptions including a guilt judgment and a narrative about what occurred during the incident. Participants then deliberated for approximately thirty minutes using either an evidence-driven or verdict-driven deliberation style before again providing case perceptions, including a guilt determination, a narrative about what happened during the incident, and an evidence recognition test. Multi-level regression analyses revealed that evidence order, deliberation style and sample interacted to influence both story consistency measures and guilt. Among students, participants in the verdict-driven deliberation condition formed more consistent pro-prosecution stories when the prosecution presented their case in story-order, while participants in the evidence-driven deliberation condition formed more consistent pro-prosecution stories when the defense's case was presented in story-order. Findings were the opposite among community members, with participants in the verdict-driven deliberation condition forming more consistent pro-prosecution stories when the defense's case was presented in story-order, and participants in the evidence-driven deliberation condition forming more consistent pro-prosecution stories when the prosecution's case was presented in story-order. Additionally several story consistency measures influenced guilt decisions. Thus there is some support for the hypothesis that story consistency mediates the influence of evidence order and deliberation style on guilt decisions.

Exploring the role of large predators in marsh food webs: evidence for a behaviorally-mediated trophic cascade

The influence of large predators on lower trophic levels in oligotrophic, structurally complex, and frequently disturbed aquatic environments is generally thought to be limited. We looked for effects of large predators in two semi-permanent, spikerush-dominated marshes by excluding large fish (>12 mm body depth) and similarly sized herpetofauna from 1 m2 cages (exclosures) for 2 weeks. The exclosures allowed for colonization by intermediate (in size and trophic position) consumers, such as small fish, shrimp, and crayfish. Exclosures were compared to control cages that allowed large fish to move freely in and out. At the end of the experiment, intermediate-consumer densities were higher in exclosures than in controls at both sites. Decapod crustaceans, especially the riverine grass shrimp (Palaemonetes paludosus), accounted for the majority of the response. Effects of large fish on shrimp were generally consistent across sites, but per capita effects were sensitive to estimates of predator density. Densities of intermediate consumers in our exclosures were similar to marsh densities, while the open controls had lower densities. This suggests that these animals avoided our experimental controls because they were risky relative to the surrounding environment, while the exclosures were neither avoided nor preferred. Although illuminating about the dynamics of open-cage experiments, this finding does not influence the main results of the study. Small primary consumers (mostly small snails, amphipods, and midges) living on floating periphyton mats and in flocculent detritus (“floc”) were less abundant in the exclosures, indicative of a trophic cascade. Periphyton mat characteristics (i.e., biomass, chlorophyll a, TP) were not clearly or consistently affected by the exclosure, but TP in the floc was lower in exclosures. The collective cascading effects of large predators were consistent at both sites despite differences in drought frequency, stem density, and productivity.

Globalization and the public provision of higher education: Empirical evidence from selected countries

This research study was designed to examine the relationship between globalization as measured by the KOF index, its related forces (economic, political, cultural and technological) and the public provision of higher education. This study is important since globalization is increasingly being associated with changes in critical aspects of higher education. The public provision of education was measured by government expenditure and educational outcomes; that is participation, gender equity and attainment. The study utilized a non-experimental quantitative research design. Data collected from secondary sources for 139 selected countries was analyzed. The countries were geographically distributed and included both developed and developing countries. The choice of countries for inclusion in the study was based on data availability. The data, which was sourced from international organizations such as the United Nations and the World Bank, were examined for different time periods using five year averages. The period covered was 1970 to 2009.^ The relationship between globalization and the higher education variables was examined using cross sectional regression analysis while controlling for economic, political and demographic factors. The major findings of the study are as follows. For the two spending models, only one revealed a significant relationship between globalization and education with the R 2 s ranging from .222 to .448 over the period. This relationship was however negative indicating that as globalization increased, spending on higher education declined. However, for the education outcomes models, this relationship was not significant. For the sub-indices of globalization, only the political dimension showed significance as shown in the spending model. Political globalization was significant for six periods with R2 s ranging from .31 to .52.^ The study concluded that the results are mixed for both the spending and outcome models. It also found no robust effects of globalization on government education provision. This finding is not surprising given the existing literature which sees mixed results on the social impact of globalization.^