Safe Reflection Through Polymorphism

Code executed in a fully reflective system switches back and forth between application and interpreter code. These two states can be seen as contexts in which an expression is evaluated. Current language implementations obtain reflective capabilities by exposing objects to the interpreter. However, in doing so these systems break the encapsulation of the application objects. In this paper we propose safe reflection through polymorphism, \ie by unifying the interface and ensuring the encapsulation of objects from both the interpreter and application context. We demonstrate a \emphhomogeneous system that defines the execution semantics in terms of itself, thus enforcing that encapsulation is not broken.

Spanish-English Codeswitching in Email Communication

While spoken codeswitching (CS) among Latinos has received significant scholarly attention, few studies have examined written CS, specifically naturally-occurring CS in email. This study contributes to an under-studied area of Latino linguistic practices by reporting the results of a study of CS in the emails of five Spanish-English bilingual Latinos. Methods are employed that are not often used in discourse analysis of email texts, namely multi-dimensional scaling and tree diagrams, to explore the contextual parameters of written Spanish-English CS systematically. Consistent with the findings of other studies of CS in CMC, English use was most associated with professional or formal contacts, and use of Spanish, the participants’ native language, was linked to intimacy, informality, and group identification. Switches to Spanish functioned to personalize otherwise transactional or work-related English-dominant emails. The article also discusses novel orthographic and linguistic forms specific to the CMC context.

Tight Genetic Linkage of Prezygotic Barrier Loci Creates a Multifunctional Speciation Island in Petunia

Most flowering plants depend on animal vectors for pollination and seed dispersal. Differential pollinator preferences lead to premating isolation and thus reduced gene flow between interbreeding plant populations [1, 2, 3 and 4]. Sets of floral traits, adapted to attract specific pollinator guilds, are called pollination syndromes [5]. Shifts in pollination syndromes have occurred surprisingly frequently [6], considering that they must involve coordinated changes in multiple genes affecting multiple floral traits. Although the identification of individual genes specifying single pollination syndrome traits is in progress in many species, little is known about the genetic architecture of coadapted pollination syndrome traits and how they are embedded within the genome [7]. Here we describe the tight genetic linkage of loci specifying five major pollination syndrome traits in the genus Petunia: visible color, UV absorption, floral scent production, pistil length, and stamen length. Comparison with other Solanaceae indicates that, in P. exserta and P. axillaris, loci specifying these floral traits have specifically become clustered into a multifunctional “speciation island” [ 8 and 9]. Such an arrangement promotes linkage disequilibrium and avoids the dissolution of pollination syndromes by recombination. We suggest that tight genetic linkage provides a mechanism for rapid switches between distinct pollination syndromes in response to changes in pollinator availabilities.

Color and Scent: How Single Genes Influence Pollinator Attraction

A major function of angiosperm flowers is the recruitment of animal pollinators that serve to transfer pollen among conspecific plants. Distinct sets of floral characteristics, called pollination syndromes, are correlated with visitation by specific groups of pollinators. Switches among pollination syndromes have occurred in many plant families. Such switches must have involved coordinated changes in multiple traits and multiple genes. Two well-studied floral traits affecting pollinator attraction are petal color and scent production. We review current knowledge about the biosynthetic pathways for floral color and scent production and their interaction at the genetic and biochemical levels. A key question in the field concerns the genes that underlie natural variation in color and scent and how such genes affect pollinator preference, reproductive isolation, and ultimately speciation.

Zidovudine impairs immunological recovery on first-line antiretroviral therapy: collaborative analysis of cohort studies in southern Africa

OBJECTIVES Zidovudine (ZDV) is recommended for first-line antiretroviral therapy (ART) in resource-limited settings. ZDV may, however, lead to anemia and impaired immunological response. We compared CD4+ cell counts over 5 years between patients starting ART with and without ZDV in southern Africa. DESIGN Cohort study. METHODS Patients aged at least 16 years who started first-line ART in South Africa, Botswana, Zambia, or Lesotho were included. We used linear mixed-effect models to compare CD4+ cell count trajectories between patients on ZDV-containing regimens and patients on other regimens, censoring follow-up at first treatment change. Impaired immunological recovery, defined as a CD4+ cell count below 100 cells/μl at 1 year, was assessed in logistic regression. Analyses were adjusted for baseline CD4+ cell count and hemoglobin level, age, sex, type of regimen, viral load monitoring, and calendar year. RESULTS A total of 72,597 patients starting ART, including 19,758 (27.2%) on ZDV, were analyzed. Patients on ZDV had higher CD4+ cell counts (150 vs.128 cells/μl) and hemoglobin level (12.0 vs. 11.0 g/dl) at baseline, and were less likely to be women than those on other regimens. Adjusted differences in CD4+ cell counts between regimens containing and not containing ZDV were -16 cells/μl [95% confidence interval (CI) -18 to -14] at 1 year and -56 cells/μl (95% CI -59 to -52) at 5 years. Impaired immunological recovery was more likely with ZDV compared to other regimens (odds ratio 1.40, 95% CI 1.22-1.61). CONCLUSION In southern Africa, ZDV is associated with inferior immunological recovery compared to other backbones. Replacing ZDV with another nucleoside reverse transcriptase inhibitor could avoid unnecessary switches to second-line ART.

Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study

BACKGROUND Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa. DESIGN Mathematical model based on longitudinal data from the Gugulethu and Khayelitsha township ART programmes in Cape Town, South Africa. METHODS Cohorts of patients on ART monitored by POC-VL, CD4 cell count or clinically were simulated. Scenario A considered the more accurate detection of treatment failure with POC-VL only, and scenario B also considered the effect on HIV transmission. Scenario C further assumed that the risk of virologic failure is halved with POC-VL due to improved adherence. We estimated the change in costs per quality-adjusted life-year gained (incremental cost-effectiveness ratios, ICERs) of POC-VL compared with CD4 and clinical monitoring. RESULTS POC-VL tests with detection limits less than 1000 copies/ml increased costs due to unnecessary switches to second-line ART, without improving survival. Assuming POC-VL unit costs between US$5 and US$20 and detection limits between 1000 and 10,000 copies/ml, the ICER of POC-VL was US$4010-US$9230 compared with clinical and US$5960-US$25540 compared with CD4 cell count monitoring. In Scenario B, the corresponding ICERs were US$2450-US$5830 and US$2230-US$10380. In Scenario C, the ICER ranged between US$960 and US$2500 compared with clinical monitoring and between cost-saving and US$2460 compared with CD4 monitoring. CONCLUSION The cost-effectiveness of POC-VL for monitoring ART is improved by a higher detection limit, by taking the reduction in new HIV infections into account and assuming that failure of first-line ART is reduced due to targeted adherence counselling.

Comparison of inorganic nitrogen uptake dynamics following snowmelt and at peak biomass in subalpine grasslands

Subalpine grasslands are highly seasonal environments and likely subject to strong variability in nitrogen (N) dynamics. Plants and microbes typically compete for N acquisition during the growing season and particularly at plant peak biomass. During snowmelt, plants could potentially benefit from a decrease in competition by microbes, leading to greater plant N uptake associated with active growth and freeze-thaw cycles restricting microbial growth. In managed subalpine grasslands, we expect these interactions to be influenced by recent changes in agricultural land use, and associated modifications in plant and microbial communities. At several subalpine grasslands in the French Alps, we added pulses of 15N to the soil at the end of snowmelt, allowing us to compare the dynamics of inorganic N uptake in plants and microbes during this period with that previously reported at the peak biomass in July. In all grasslands, while specific shoot N translocation (per g of biomass) of dissolved inorganic nitrogen (DIN) was two to five times greater at snowmelt than at peak biomass, specific microbial DIN uptakes were similar between the two sampling dates. On an area basis, plant communities took more DIN than microbial communities at the end of snowmelt when aboveground plant biomasses were at least two times lower than at peak biomass. Consequently, inorganic N partitioning after snowmelt switches in favor of plant communities, allowing them to support their growing capacities at this period of the year. Seasonal differences in microbial and plant inorganic N-related dynamics were also affected by past (terraced vs. unterraced) rather than current (mown vs. unmown) land use. In terraced grasslands, microbial biomass N remained similar across seasons, whereas in unterraced grasslands, microbial biomass N was higher and microbial C : N lower at the end of snowmelt as compared to peak biomass. Further investigations on microbial community composition and their organic N uptake dynamics are required to better understand the decrease in microbial DIN uptake.

The evolution of host associations in the parasitic wasp genus Ichneumon (Hymenoptera: Ichneumonidae): convergent adaptations to host pupation sites

Background: The diversification of organisms with a parasitic lifestyle is often tightly linked to the evolution of their host associations. If a tight host association exists, closely related species tend to attack closely related hosts; host associations are less stable if associations are determined by more plastic traits like parasitoid searching and oviposition behaviour. The pupal-parasitoids of the genus Ichneumon attack a variety of macrolepidopteran hosts.They are either monophagous or polyphagous, and therefore offer a promissing system to investigate the evolution of host associations. Ichneumon was previously divided into two groups based on general body shape; however, a stout shape has been suggested as an adaptation to buried host pupation sites, and might thus not represent a reliable phylogenetic character. Results: We here reconstruct the first molecular phylogeny of the genus Ichneumon using two mitochondrial (CO1 and NADH1) and one nuclear marker (28S). The resulting phylogeny only supports monophyly of Ichneumon when Ichneumon lugens Gravenhorst, 1829 (formerly in Chasmias, stat. rev.) and Ichneumon deliratorius Linnaeus, 1758 (formerly Coelichneumon) are included. Neither parasitoid species that attack hosts belonging to one family nor those attacking butterflies (Rhopalocera) form monophyletic clades. Ancestral state reconstructions suggest multiple transitions between searching for hosts above versus below ground and between a stout versus elongated body shape. A model assuming correlated evolution between the two characters was preferred over independent evolution of host-searching niche and body shape. Conclusions: Host relations, both in terms of phylogeny and ecology, evolved at a high pace in the genus Ichneumon. Numerous switches between hosts of different lepidopteran families have occurred, a pattern that seems to be the rule among idiobiont parasitoids. A stout body and antennal shape in the parasitoid female is confirmed as an ecological adaptation to host pupation sites below ground and has evolved convergently several times. Morphological characters that might be involved in adaptation to hosts should be avoided as diagnostic characters for phylogeny and classification, as they can be expected to show high levels of homoplasy.

Synthesis and Redox and Photophysical Properties of Benzodifuran-Spiropyran Ensembles

Two benzodifuran (BDF)-coupled spiropyran (SP) systems and their BDF reference compounds were obtained in good yields through HuisgenMeldalSharpless click chemistry and then subjected to investigation of their electrochemical and photophysical properties. In both SP and merocyanine (MC) forms of the coupled molecules, the BDF-based emission is quenched to around 1 of the quantum yield of emission from the BDF reference compounds. Based on electrochemical data, this quenching is attributed to oxidative electron-transfer quenching. Irradiation at 366nm results in ring opening to the MC forms of the BDF-coupled SP compounds and the SP reference compound with a quantum efficiency of about 50. The rate constants for the thermal ring closing are approximately 3.4x103s1. However, in the photostationary states the MC fractions of the coupled molecules are substantially lower than that of the reference SP compound, attributed to the observed acceleration of the ring-closing reaction upon irradiation. As irradiation at 366nm invariably also excites higher-energy transitions of the BDF units in the coupled compounds, the ring-opening reaction is accelerated relative to the SP reference, which results in lower MC fractions in the photostationary state. Reversible photochromism of these BDF-coupled SP compounds renders them promising in the field of molecular switches.

A model of late long-term potentiation simulates aspects of memory maintenance.

Late long-term potentiation (L-LTP) denotes long-lasting strengthening of synapses between neurons. L-LTP appears essential for the formation of long-term memory, with memories at least partly encoded by patterns of strengthened synapses. How memories are preserved for months or years, despite molecular turnover, is not well understood. Ongoing recurrent neuronal activity, during memory recall or during sleep, has been hypothesized to preferentially potentiate strong synapses, preserving memories. This hypothesis has not been evaluated in the context of a mathematical model representing ongoing activity and biochemical pathways important for L-LTP. In this study, ongoing activity was incorporated into two such models - a reduced model that represents some of the essential biochemical processes, and a more detailed published model. The reduced model represents synaptic tagging and gene induction simply and intuitively, and the detailed model adds activation of essential kinases by Ca(2+). Ongoing activity was modeled as continual brief elevations of Ca(2+). In each model, two stable states of synaptic strength/weight resulted. Positive feedback between synaptic weight and the amplitude of ongoing Ca(2+) transients underlies this bistability. A tetanic or theta-burst stimulus switches a model synapse from a low basal weight to a high weight that is stabilized by ongoing activity. Bistability was robust to parameter variations in both models. Simulations illustrated that prolonged periods of decreased activity reset synaptic strengths to low values, suggesting a plausible forgetting mechanism. However, episodic activity with shorter inactive intervals maintained strong synapses. Both models support experimental predictions. Tests of these predictions are expected to further understanding of how neuronal activity is coupled to maintenance of synaptic strength. Further investigations that examine the dynamics of activity and synaptic maintenance can be expected to help in understanding how memories are preserved for up to a lifetime in animals including humans.

The bivalency effect in task switching: General and enduring

The purpose of this study was to investigate the generality and temporal endurance of the bivalency effect in task switching. This effect refers to the slowing on univalent stimuli that occurs when bivalent stimuli appear occasionally. We used a paradigm involving predictable switches between 3 simple tasks, with bivalent stimuli occasionally occurring on one of the tasks. The generality of the bivalency effect was investigated by using different tasks and different types of bivalent stimuli, and the endurance of this effect was investigated across different intertrial intervals (ITIs) and across the univalent trials that followed trials with bivalent stimuli. In 3 experiments, the results showed a general, robust, and enduring bivalency effect for all ITI conditions. Although the effect declined across trials, it remained significant for about 4 trials following one with a bivalent stimulus. Our findings emphasise the importance of top–down processes in task-switching performance. (PsycINFO Database Record (c) 2012 APA, all rights reserved)

Turning univalent stimuli bivalent: Synesthesia can cause cognitive conflict in task switching

In this study we investigated whether synesthetic color experiences have similar effects as real colors in cognitive conflict adaptation. We tested 24 synesthetes and two yoke-matched control groups in a task-switching experiment that involved regular switches between three simple decision tasks (a color decision, a form decision, and a size decision). In most of the trials the stimuli were univalent, that is, specific for each task. However, occasionally, black graphemes were presented for the size decisions and we tested whether they would trigger synesthetic color experiences and thus, turn them into bivalent stimuli. The results confirmed this expectation. We were also interested in their effect for subsequent performance (i.e., the bivalency effect). The results showed that for synesthetic colors the bivalency effect was not as pronounced as for real colors. The latter result may be related to differences between synesthetes and controls in coping with color conflict.

Metamagnetic Copper(II) Diphosphonates with Layered Structures

Compounds [NH3(CH2)4NH3]Cu3(hedp)2·2H2O (1) and [NH3(CH2)3NH3]Cu3(hedp)2·3.5H2O (2), where hedp represents 1-hydroxyethylidenediphosphonate, exhibit two-dimensional structures closely related to each other. The anionic layers with composition {Cu3(hedp)2}n2n- contain four- and eight-membered rings assembled from vertex-sharing {CuO4} units and {CPO3} tetrahedra. The protonated diamines and lattice water fill the interlayer spaces. Crystal data for 2:  space group P1̄, a = 8.0315(4), b = 11.3713(6), c = 13.3117(7) Å, α = 97.122(1), β = 103.187(1), γ = 108.668(1)°, V = 1095.5(1) Å3, Z = 2. Magnetic properties of the two compounds have been investigated. Both show typical metamagnetic behaviors at low temperature. The critical field at which the antiferromagnetic ground-state switches to a ferrimagnetic state is ∼48 Oe for 1 and 185 Oe for 2 at about 2 K.

The genetics of reproductive organ morphology in two Petunia species with contrasting pollination syndromes

Main conclusion Switches between pollination syndromes have happened frequently during angiosperm evolution. Using QTL mapping and reciprocal introgressions, we show that changes in reproductive organ morphology have a simple genetic basis. In animal-pollinated plants, flowers have evolved to optimize pollination efficiency by different pollinator guilds and hence reproductive success. The two Petunia species, P. axillaris and P. exserta, display pollination syndromes adapted to moth or hummingbird pollination. For the floral traits color and scent, genetic loci of large phenotypic effect have been well documented. However, such large-effect loci may be typical for shifts in simple biochemical traits, whereas the evolution of morphological traits may involve multiple mutations of small phenotypic effect. Here, we performed a quantitative trait locus (QTL) analysis of floral morphology, followed by an in-depth study of pistil and stamen morphology and the introgression of individual QTL into reciprocal parental backgrounds. Two QTLs, on chromosomes II and V, are sufficient to explain the interspecific difference in pistil and stamen length. Since most of the difference in organ length is caused by differences in cell number, genes underlying these QTLs are likely to be involved in cell cycle regulation. Interestingly, conservation of the locus on chromosome II in a different P. axillaris subspecies suggests that the evolution of organ elongation was initiated on chromosome II in adaptation to different pollinators. We recently showed that QTLs for pistil and stamen length on chromosome II are tightly linked to QTLs for petal color and volatile emission. Linkage of multiple traits will enable major phenotypic change within a few generations in hybridizing populations. Thus, the genomic architecture of pollination syndromes in Petunia allows for rapid responses to changing pollinator availability.

Activation of metabotropic glutamate 5 and NMDA receptors underlies the induction of persistent bursting and associated long-lasting changes in CA3 recurrent connections.

The aim of this study was to describe the induction and expression mechanisms of a persistent bursting activity in a horizontal slice preparation of the rat limbic system that includes the ventral part of the hippocampus and the entorhinal cortex. Disinhibition of this preparation by bicuculline led to interictal-like bursts in the CA3 region that triggered synchronous activity in the entorhinal cortex. Washout of bicuculline after a 1 hr application resulted in a maintained production of hippocampal bursts that continued to spread to the entorhinal cortex. Separation of CA3 from the entorhinal cortex caused the activity in the latter to become asynchronous with CA3 activity in the presence of bicuculline and disappear after washout; however, in CA3, neither the induction of bursting nor its persistence were affected. Associated with the CA3 persistent bursting, a strengthening of recurrent collateral excitatory input to CA3 pyramidal cells and a decreased input to CA3 interneurons was found. Both the induction of the persistent bursting and the changes in synaptic strength were prevented by antagonists of metabotropic glutamate 5 (mGlu5) or NMDA receptors or protein synthesis inhibitors and did not occur in slices from mGlu5 receptor knock-out mice. The above findings suggest potential synaptic mechanisms by which the hippocampus switches to a persistent interictal bursting mode that may support a spread of interictal-like bursting to surrounding temporal lobe regions.