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HBeAg seroconversion is an important stage in the evolution of a chronic hepatitis B virus (HBV) infection that usually leads to control of viral replication and a reduced risk for liver cirrhosis and cancer. Since current therapies for the HBV-associated liver inflammation that is known as chronic hepatitis B (CHB). Rarely induce permanent HBeAg seroconversion, there is a need to understand the mechanisms responsible for the purpose of identifying new therapeutic targets. Currently, the most widely accepted hypothesis is that the patient’s humoral and cellular immune responses to the HBV initiate HBeAg seroconversion. Although we accept that this hypothesis cannot be excluded, we propose an alternative that is consistent with published data on HBeAg seroconversion. We postulate, as others have, that the HBeAg suppresses the immune response to the HBV. However, production of the HBeAg incurs a metabolic cost to the hepatocyte which reduces the replicative capacity of the virus. Consequently, HBeAg-negative viruses replicate faster than HBeAg-positive viruses. HBeAg-negative variants arise de novo; and when their frequency in the population is low they have a replicative advantage. However, they also benefit from the immunosuppressive effects of the HBeAg-positive viruses in the population. As HBeAg-negative variants increase in frequency and HBeAg levels fall, the immune system recognizes the HBV, and HBeAg seroconversion occurs as a consequence of frequency-dependent selection acting on HBeAg-negative variants. This hypothesis explains the wide inter-individual variation in age of seroconversion, the increased rate of seroconversion during anti-viral treatment and the phenomena of both spontaneous and post-treatment HBeAg reversions (in which patients cycle between the HBeAg-positive and negative phases of their infection).

Air temperature is correlated with precipitation oxygen isotope (δ18Oprcp) variability for much of the eastern and central United States, but the nature of this δ18Oprcp‐temperature relationship is largely based on data coarsely aggregated at a monthly resolution. We constructed a database of 6177 weeks of isotope and precipitation‐day air temperature data from 25 sites to determine how more precise data change our understanding of this classic relationship. Because the δ18Oprcp‐temperature relationship is not perfectly linear, trends in the regression residuals suggest the influence of additional environmental factors such as moisture recycling and extratropical cyclone interactions. Additionally, the temporal relationships between δ18Oprcp and temperature observed in the weekly data at individual sites can explain broader spatial patterns observed across the study region. For 20 of 25 sites, the δ18Oprcp‐temperature relationship slope is higher for colder precipitation than for warmer precipitation. Accordingly, northern and western sites with relatively more cold precipitation events have steeper overall relationships with higher slope values than southeastern sites that have more warm precipitation events. Although the magnitude of δ18Oprcp variability increases to the north and west, the fraction of δ18Oprcp variability explained by temperature increases due to wider annual temperature ranges, producing stronger relationships in these regions. When our δ18Oprcp‐temperature data are grouped by month, we observe significant variations in the relationship from month to month. This argues against a principal causative role for temperature and suggests the existence of an alternative environmental control on δ18Oprcp values that simply covaries seasonally with temperature.

Background Local adaptation, the differential success of genotypes in their native versus foreign environment, arises from various evolutionary processes, but the importance of concurrent abiotic and biotic factors as drivers of local adaptation has only recently been investigated. Local adaptation to biotic interactions may be particularly important for plants, as they associate with microbial symbionts that can significantly affect their fitness and may enable rapid evolution. The arbuscular mycorrhizal (AM) symbiosis is ideal for investigations of local adaptation because it is globally widespread among most plant taxa and can significantly affect plant growth and fitness. Using meta-analysis on 1170 studies (from 139 papers), we investigated the potential for local adaptation to shape plant growth responses to arbuscular mycorrhizal inoculation. Results The magnitude and direction for mean effect size of mycorrhizal inoculation on host biomass depended on the geographic origin of the soil and symbiotic partners. Sympatric combinations of plants, AM fungi, and soil yielded large increases in host biomass compared to when all three components were allopatric. The origin of either the fungi or the plant relative to the soil was important for explaining the effect of AM inoculation on plant biomass. If plant and soil were sympatric but allopatric to the fungus, the positive effect of AM inoculation was much greater than when all three components were allopatric, suggesting potential local adaptation of the plant to the soil; however, if fungus and soil were sympatric (but allopatric to the plant) the effect of AM inoculation was indistinct from that of any allopatric combinations, indicating maladaptation of the fungus to the soil. Conclusions This study underscores the potential to detect local adaptation for mycorrhizal relationships across a broad swath of the literature. Geographic origin of plants relative to the origin of AM fungal communities and soil is important for describing the effect of mycorrhizal inoculation on plant biomass, suggesting that local adaptation represents a powerful factor for the establishment of novel combinations of fungi, plants, and soils. These results highlight the need for subsequent investigations of local adaptation in the mycorrhizal symbiosis and emphasize the importance of routinely considering the origin of plant, soil, and fungal components. Electronic supplementary material The online version of this article (doi:10.1186/s12862-016-0698-9) contains supplementary material, which is available to authorized users.

Plants form belowground associations with mycorrhizal fungi in one of the most common symbioses on Earth. However, few large-scale generalizations exist for the structure and function of mycorrhizal symbioses, as the nature of this relationship varies from mutualistic to parasitic and is largely context-dependent. We announce the public release of MycoDB, a database of 4,010 studies (from 438 unique publications) to aid in multi-factor meta-analyses elucidating the ecological and evolutionary context in which mycorrhizal fungi alter plant productivity. Over 10 years with nearly 80 collaborators, we compiled data on the response of plant biomass to mycorrhizal fungal inoculation, including meta-analysis metrics and 24 additional explanatory variables that describe the biotic and abiotic context of each study. We also include phylogenetic trees for all plants and fungi in the database. To our knowledge, MycoDB is the largest ecological meta-analysis database. We aim to share these data to highlight significant gaps in mycorrhizal research and encourage synthesis to explore the ecological and evolutionary generalities that govern mycorrhizal functioning in ecosystems. ispartof: Scientific Data vol:10 issue:3 ispartof: location:England status: published

Although the Atacama Desert is one of the driest places on earth there are several halite caves in the Oligocene-Miocene outcrop of evaporites that forms the Cordillera de la Sal. The caves contain a variety of deposits including speleothems, allogenic sediments, and archaeological remains that have provided information on cave evolution and proxy information on past climates in the area. This study presents the first report of monocrystalline halite stalactites whose initial formation and subsequent evolution are controlled by (1) the degree of supersaturation of the feeding solution, (2) capillary and/or gravity flow along the speleothem, and (3) air currents in the cave. Also, we report a new cave mineral (atacamite) together with a zeolite (clinoptilolite), where genesis was controlled by thermal fluids rising under pressure along a fault plane. Analysis and radiocarbon dating of the allogenic sediments and archaeologic remains shows that the halite caves of Atacama are very young and that development is rapid during rare floods brought on by sudden, short rainstorms that may only affect a single stream catchment. By contrast, between these rare events, which may be several hundred years apart, there is little or no cave development.

STUDY DESIGN A parallel group design with repeated measures using a cadaver model was employed. OBJECTIVE The purpose of this study was to evaluate and compare lumbar spine motion generated in the presence of spinal instabilities during common hospital moves using different transfer techniques. SUMMARY OF BACKGROUND DATA Up to 25% of spinal cord injuries may occur during initial management of the patient with a compromised spinal column, when multiple transfers between diagnostic locations and operating, recovery and hospital rooms are often required. Few studies have compared methods of moving patients with lumbar spinal column injuries in hospital settings. METHODS A global instability was created in 3 cadavers at L1 and sensors were attached to T12 and L2. A 3-dimensional electromagnetic tracking system (Liberty, Polhemus Inc) was used to measure flexion, lateral bending, and axial rotation while moving a cadaver from one bed to another to compare 2 transfer techniques used in hospitals: manual transfer and the On3, a motorized lateral transfer device (Hill-Rom, Batesville, IN). RESULTS Significant increases in lumbar angulations (P

Object. The purpose of this study was to compare manual maneuvering with the use of a Jackson table when moving patients with cervical spine instability from the supine to the surgically appropriate prone position. Methods. The range of motion (ROM) of the cervical spine of a fresh cadaver was measured. A ligamentous instability was created at the C5–6 level, and the increased ROM was confirmed. Sensors for an electromagnetic motion analysis device were fixed to the anterior portions of the C-5 and C-6 vertebral bodies (VBs) using machined polyethylene mounts and carbon fiber rods that were inserted into the VBs. The sensors were used to measure cervical flexion, lateral bending, and axial rotation during the two transfer procedures. The cadaver was then moved from the supine position on a hospital bed to the prone position for surgery. The manual technique was performed by four trained individuals who moved the cadaver from the hospital bed while rotating it 180° axially onto the surgical table. In using the Jackson table, the cadaver was moved from the bed to the table in the supine position and then the Jackson table rotated the cadaver to the prone position. The two techniques were tested with and without the use of a collar and were repeated five times. Results. Analysis of the data indicated that when moving a patient into the prone surgical position, the use of a cervical collar and the Jackson table significantly reduced the cervical motion in all angular planes compared with that of manual transfer. Conclusions. The use of a cervical collar and the Jackson table may reduce the possibility of further spinal cord compromise. Because manual transfers are performed routinely, this warrants further study.

BACKGROUND: The main comorbidities associated with spinal cord injury patients are secondary to immobilization. Kinetic bed therapy is used currently to reduce the complications associated with immobilization, but the effect on the unstable spine has not been quantified. The purpose of this study was to compare the motion in the cervical and thoracolumbar spine when cadavers with spinal instabilities are log rolled (LR) on a standard hospital bed or rotated on a RotoRest kinetic treatment table (KTT). METHODS: Cervical and lumbar instabilities were created surgically in three embalmed cadavers. An electromagnetic tracking device was used to measure the three-dimensional segmental motion generated at C5 to C6 and T12 to L2 during LR and KTT treatments. RESULTS: In both the cervical and lumbar spine, significantly more motion was observed during LR than KTT treatment. CONCLUSIONS: We found that in cadavers with severely unstable cervical spine, rotation using a KTT produced less flexion and lateral bending than the LR. Also, in cadavers with severely unstable lumbar spine, treatment with the KTT produced less axial rotation than the LR. Currently, we think that the best way to immobilize the spine while still allowing therapeutic motion is through the use of a KTT. Language: en

Recently, we reported the discovery of several potential rodent reservoirs of hantaviruses in western (Holochilus chacarius) and eastern Paraguay (Akodon montensis, Oligoryzomys chacoensis, and O. nigripes). Comparisons of the hantavirus S- and M-segments amplified from these four rodents revealed significant differences from each another and from other South American hantaviruses. The ALP strain from the semiarid Chaco ecoregion clustered with Leguna Negra and Rio Mamore (LN/RM), whereas the BMJ-NEB strain from the more humid lower Chaco ecoregion formed a clade with Oran and Bermejo. The other two strains, AAI and IP37/38, were distinct from known hantaviruses. With respect to the S-segment sequence, AAI from eastern Paraguay formed a clade with ALP/LN/RM, but its M-segment clustered with Pergamino and Maciel, suggesting a possible reassortment. AAI was found in areas experiencing rapid land cover fragmentation and change within the Interior Atlantic Forest. IP37/38 did not show any strong association with any of the known hantavirus strains.

Long-distance seed dispersal influences many key aspects of the biology of plants, including spread of invasive species, metapopulation dynamics, and diversity and dynamics in plant communities. However, because long-distance seed dispersal is inherently hard to measure, there are few data sets that characterize the tails of seed dispersal curves. This paper is structured around two lines of argument. First, we argue that long-distance seed dispersal is of critical importance and, hence, that we must collect better data from the tails of seed dispersal curves. To make the case for the importance of long-distance seed dispersal, we review existing data and models of long-distance seed dispersal, focusing on situations in which seeds that travel long distances have a critical impact (colonization of islands, Holocene migrations, response to global change, metapopulation biology). Second, we argue that genetic methods provide a broadly applicable way to monitor long-distance seed dispersal; to place this argument in context, we review genetic estimates of plant migration rates. At present, several promising genetic approaches for estimating long-distance seed dispersal are under active development, including assignment methods, likelihood methods, genealogical methods, and genealogical/demographic methods. We close the paper by discussing important but as yet largely unexplored areas for future research.

Besides woody cone scales, certain species of wind-dispersed pines (Pinus) have spines on their scales as a putative form of defense against seed predators. We tested whether spines differentially deterred seed predators foraging on closed and open pine cones. Red Crossbills (Loxia curvirostra) were selected as the seed predator because they commonly forage on these cones. We timed crossbills foraging on closed and open pine cones with and without spines. Crossbills did not require more time to remove seeds from closed ponderosa pine (P. ponderosa) cones with spines. However, crossbills required significantly more time (18-34%) to remove seeds from open ponderosa pine and Table Mountain pine (P. pungens) cones with spines than from cones whose spines had been removed. Moreover, experiments designed to isolate the effect of spines on the perching and probing behavior of crossbills revealed that spines hindered both activities additively. These experimental results were consistent with our phylogenetic analyses of 21 species of hard pines (subgenus Pinus). Whereas the evolution of changes in the length of time seeds are retained in closed cones and that of changes in the presence of spines appear independent, changes in the length of time seeds are retained in open cones were associated with changes in the presence or development of spines. Therefore, pines that retain seeds in open but not closed cones for extended periods tend to have well-developed spines. This illustrates the complementarity of experimental approaches and explicit phylogenetic mod- els in elucidating ecological processes.

In their classic study, Alston and Turner (American Journal of Botany, vol. 50, 159-173, 1963) documented extensive hybridization among four morphologically distinct Baptisia species native to East Texas. While Alston and Turner found putative F1 hybrids in great numbers, they found no evidence of backcrossing. In this study prezygotic and postzygotic reproductive barriers between two of these species, B. leucophaea and B. sphaerocarpa, were investigated and found to be quite weak. Flowering times overlap and bumble bees were observed visiting both species and intermediate hybrids. While pollinator constancy in flights between B. leucophaea and B. sphaerocarpa was moderately strong, significant levels of constancy were not observed in flights involving hybrids and either parental species. Thus, backcrossing was not impeded by pollinator behavior. Further, hybrid pollen was highly stainable (93.5%) and able to effectively set seed in crossing experiments with both parental species. Pollinator behavior was compared in experimental populations with and without hybrid ramets and found to differ between these two treatments. Hybrids were found to facilitate pollinator movement between species. In total, these results suggest that reproductive isolation is not responsible for the rarity of backcrossing in naturally hybridizing B. leucophaea and B. sphaerocarpa populations.

Plant mating systems often involve a mixture of self fertilizations and outcross fertilizations. The degree of selfing has a large impact on the genetic composition of natural populations and on the evolution of the mating system itself in response to such factors as inbreeding depression. This paper describes a means of estimating the long-term rate of self-fertilization from samples of alleles taken from individuals in a population. Use is made of the genealogy of pairs of alleles at a locus within individuals and pairs between individuals. The degree of selfing is closely related to the extent to which the number of nucleotide sites differing within an individual is reduced relative to the number differing between individuals. Importantly, the estimate of long-term selfing is largely independent of population size and is not affected by historical fluctuations in population size; instead it responds directly to the mating system itself. The approach outlined here is most appropriate to evolutionary problems in which the long-term nature of the mating system is of interest, such as to determine the relationship between prior inbreeding and inbreeding depression.

We obtained a microsatellite-enriched genomic library isolated from the tissue of a single columbine (Aquilegia sp.) plant taken from a southwestern USA natural population. The primers developed for these microsatellite loci performed consistently in polymerase chain reactions and yielded multiallelic genotypes with relatively high observed heterozygosities. We describe polymerase chain reaction primers and conditions to amplify 16 unique, codominant di-, tri- and tetra-nucleotide microsatellite DNA loci so that other population biology researchers using columbine natural populations as a model system may benefit.

Einleitung und Ziele: Die autologe Nerventransplantation bei überkritischen peripheren Nervendefekten ist eine in der rekonstruktiven Plastischen Chirurgie erfolgreich etablierte Methode. Durch die Entwicklung bioartifizieller Nervenleitschienen erhofft man sich, einerseits die Morbidität [for full text, please go to the a.m. URL], 44. Jahrestagung der Deutschen Gesellschaft der Plastischen, Rekonstruktiven und Ästhetischen Chirurgen (DGPRÄC), 17. Jahrestagung der Vereinigung der Deutschen Ästhetisch-Plastischen Chirurgen (VDÄPC)

One of the major problems faced by conservation biologists is the allocation of scarce resources to an overwhelmingly large number of species in need of preservation efforts. Both demographic and genetic information have been brought to bear on this problem; however, the role of information obtained from genetic markers has largely been limited to the characterization of gene frequencies and patterns of diversity. While the genetic consequences of rarity may be a contributing factor to endangerment, it is widely recognized that demographic factors often may be more important. Because patterns of genetic marker variation are influenced by the same demographic factors of interest to the conservation biologist, it is possible to extract useful demographic information from genetic marker data. Such an approach may be productive for determining plant mating systems, inbreeding depression, effective population size, and metapopulation structure. In many cases, however, data consisting only of marker frequencies are inadequate for these purposes. Development of genealogical based analytical methods coupled with studies of DNA sequence variation within and among populations is likely to yield the most information on demographic processes from genetic marker data. Indeed, in some cases it may be the only means of obtaining information on the long-term demographic properties that may be most useful for determining the future prospects of a species of interest.

The mechanisms underlying the high levels of hepatitis B virus (HBV) replication that cause hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (e−CHB) are unknown. Impaired anti-HBV immunity, which may be measurable as a relaxation of selection pressure on the virus, is possible. A group of Tongans (n = 345) with a chronic HBV infection, including seven with e−CHB, were genotyped at HLA class I. The repertoire of HBV core-gene codons under positive selection pressure was defined by phylogenetic analysis (by using the paml program) of 708 cloned sequences extracted from the 67 of these 345 subjects with the same repertoire of HLA class I alleles as the seven e−CHB individuals and matched controls (see below). The frequency of non-synonymous mutations at these codons was measured in longitudinal data from 15 subjects. Finally, the number of non-synonymous mutations at these codons was compared in seven groups comprised of one subject with e−CHB and 1–3 HLA class I-matched controls with an inactive, HBeAg-negative chronic HBV infection (e−InD). Nineteen codons in the core gene were under positive selection pressure. There was a high frequency of new non-synonymous mutations at these codons (PP = 0.02) in HBV from subjects with e−CHB (4.4±0.5 codons per subject) versus those with e−InD (6.4±0.4 codons per subject). There is a subtle relaxation in selection pressure on the HBV core gene in e−CHB. This may be due to impaired antiviral immunity, and could contribute to the high levels of viral replication that cause liver inflammation in this disease.

Background: National health strategies have called for an expansion of the role of primary care in England to increase access to sexual health services. However, there is little guidance for service planners and commissioners as to the public health impact of different combinations of specialist genitourinary medicine (GUM) clinics and primary care based services for local populations. Service planning for infectious diseases like sexually transmitted infections (STI) is further complicated because the goal of early detection and treatment is not only to improve the health of the individual, but to benefit the wider population and reduce future treatment costs by preventing onward transmission. Therefore, we are developing a survey tool that will enable service planners to better understand the needs of their local STI care-seeking population and which will help inform evidence-based decision-making about current and future service configurations. Here we describe the rationale and development of this survey tool.Methods/Design: A pen-and-paper questionnaire asking about sociodemographics, reasons for attendance, care pathways, and recent sexual risk behaviours, is being developed for patients to complete in waiting rooms of diverse clinical services, including GUM clinics and primary-care based services in sociodemographically- and geographically-contrasting populations in England. The questionnaire was cognitively tested before being piloted. In the pilot, 67% of patients participated, of whom 84% consented to our linking their questionnaire to data on STI testing and diagnosis and partner notification outcomes from their clinical records.Discussion: The pilot study suggests that both the questionnaire and its linkage to routinely-collected clinical data are likely to be acceptable to patients. By supplementing existing surveillance, data gathered by the survey tool will inform service planners' and providers' understanding of the needs and care-pathways of their patients, facilitating improved services and greater public health benefit.

Although a major component of fitness, male reproductive success is generally extremely difficult to estimate. As a result, genetic methods and maximum likelihood models have been developed to estimate male parentage, but all are limited in practice by the degree of genetic variation observable. Scoring individuals phenotypically at a large number of random loci exhibiting dominance (e.g. RAPD markers) may provide a means of detecting sufficient genetic variation. Dominance, however, represents a loss of information and therefore greater variation in the estimate of paternity. A mixture model describing mating in a population is presented to quantify the trade-off between marker types when estimates of male fertility are sought. A sample size 1.5-2.0 times greater is required for dominant markers under some conditions to obtain the same confidence in fertility estimates as for codominant markers, although with large sample sizes the fertility estimates are similar for either marker type. Since the number of dominant DN A markers is not limited in the same manner as is the number of codominant protein markers, one's confidence in the estimates can be increased above that possible from proteins by surveying additional loci. However, for a fixed sample size a trade-off exists between the number of progeny assayed per female and the number of loci surveyed. In many cases more progeny per female provide better estimates of fertility than more loci.

Although numerous exceptions are well known, organelle DNA is often exclusively or predominantly maternally inherited. In such cases, maternal inheritance is often documented by the study of progeny derived from crosses between parents with distinguishable organelle genotypes. These studies generally detect a single type of progeny, those containing organelles derived from only one of the parents; no progeny containing organelles derived either from the opposite parent or from both parents are found. However, in most cases the number of progeny examined is quite small. I present a simple binomial model of organelle inheritance to determine the power of such experiments to distinguish between the hypothesis of strict maternal inheritance and a more complex hypothesis involving the presence of both organelle types within a progeny array. Extremely large sample sizes of progeny are required to distinguish these two hypotheses with reasonable confidence when organelle transmission is not strictly maternal. As a result, studies involving simple progeny testing may be misleading. Larger samples, more complex breeding designs, or more sensitive molecular methods are required to document adequately strict maternal inheritance of organelles.

Although the Cordillera de la Sal, close to San Pedro de Atacama (Chile), is one of the driest places on Earth, it contains extensive cave systems that have developed in halite. A detailed morphological study of these caves, combined with 16 AMS radiocarbon ages on wood and bone fragments recovered from cave ceilings and diamictons, have allowed us to define when these systems formed and when sediments were emplaced. The sometimes huge cave passages appear to have formed in less than 2000 years by a succession of short-lived flash floods, probably after single extreme rain events.

A complete assessment of population growth and viability from field census data often requires complex data manipulations, statistical routines, mathematical tools, programming environments, and graphical capabilities. We therefore designed an R package called popbio to facilitate both the construction and analysis of projection matrix models. The package consists primarily of the R translation of MATLAB code found in Caswell (2001) and Morris and Doak (2002) for the analysis of projection matrix models. The package also includes methods to estimate vital rates and construct projection matrix models from census data typically collected in plant demography studies. In these studies, vital rates can often be estimated directly from annual censuses of tagged individuals using transition frequency tables. Because the construction of projection matrix models requires careful management of census data, we describe the steps to construct a projection matrix in detail.

The nature of heterotachy at the center of recent controversy over the relative performance of tree-building methods is different from the form of heterotachy that has been inferred in empirical studies. The latter have suggested that proportions of variable sites (p v a r ) vary among orthologues and among paralogues. However, the strength of this inference, describing what may be one of the most important evolutionary properties of sequence data, has remained weak. Consequently, other models of sequence evolution have been proposed to explain some long-branch attraction (LBA) problems that could be attributed to differences in p v a r . For an empirical case with plastid and eubacterial RNA polymerase sequences, we confirm using capture-recapture estimates and simulations that p v a r can differ among orthologues in anciently diverged evolutionary lineages. We find that parsimony and a least squares distance method that implements an overly simple model of sequence evolution are susceptible to LBA induced by this form of heterotachy. Although homogeneous maximum likelihood inference was found to be robust to model misspecification in our specific example, we caution against assuming that it will always be so.

Hantaviruses represent an important and growing source of disease emergence in both established and developing countries. The New World hantaviruses have been touted as potential biological weapons because of their lethality to humans and high infectivity as an aerosol. It is also important to acknowledge the threat that hantaviruses can represent to US troops that operate in a foreign territory endemic for hantavirus infection, as was demonstrated in the Korean War. Effective vaccines, immunotherapeutics and antivirals for the prophylaxis or treatment of hantaviral infections are not available. Recent evidence that hantaviruses are prone to error catastrophe opens the door to the development of new therapeutic strategies. Possible future directions for applying lethal mutagenesis as a strategy for the development of novel and more effective antiviral therapies for treatment of hantavirus infections are discussed.

In this paper we present a brief overview of the ΦLOG project, aimed at the development of a domain specific framework for the rapid prototyping of applications in evolutionary biology. This includes the development of a domain specific language, called ΦLOG, and an agent-based implementation for the monitoring and execution of ΦLOG’s programs. A ΦLOG program – representing an intended application from an evolutionary biologist – is a specification of what to do to achieve her/his goal. The execution and monitoring component of our system will automatically figure out how to do it. We achieve that by viewing the available bioinformatic tools and data repositories as web services and casting the problem of execution of a sequence of bioinformatic services (possibly with loops, branches, and conditionals, specified by biologists) as the web services composition problem.

Domain experts think and reason at a high level of abstraction when they solve problems in their domain of expertise. We present the design and motivation behind a domain specific language (DSL), called /spl Phi/LOG, to enable biologists (domain experts) to program solutions to phylogenetic inference problems at a very high level of abstraction. The implementation infrastructure (interpreter, compiler, debugger) for the DSL is automatically obtained through a software engineering framework based on denotational semantics and logic programming.

Relatedness between individuals is central to many studies in genetics and population biology. A variety of estimators have been developed to enable molecular marker data to quantify relatedness. Despite this, no effort has been given to characterize the traditional maximum-likelihood estimator in relation to the remainder. This article quantifies its statistical performance under a range of biologically relevant sampling conditions. Under the same range of conditions, the statistical performance of five other commonly used estimators of relatedness is quantified. Comparison among these estimators indicates that the traditional maximum-likelihood estimator exhibits a lower standard error under essentially all conditions. Only for very large amounts of genetic information do most of the other estimators approach the likelihood estimator. However, the likelihood estimator is more biased than any of the others, especially when the amount of genetic information is low or the actual relationship being estimated is near the boundary of the parameter space. Even under these conditions, the amount of bias can be greatly reduced, potentially to biologically irrelevant levels, with suitable genetic sampling. Additionally, the likelihood estimator generally exhibits the lowest root mean-square error, an indication that the bias in fact is quite small. Alternative estimators restricted to yield only biologically interpretable estimates exhibit lower standard errors and greater bias than do unrestricted ones, but generally do not improve over the maximum-likelihood estimator and in some cases exhibit even greater bias. Although some nonlikelihood estimators exhibit better performance with respect to specific metrics under some conditions, none approach the high level of performance exhibited by the likelihood estimator across all conditions and all metrics of performance.

Domain experts think and reason at a high level of abstraction when they solve problems in their domain of expertise. We present the design and motivation behind a domain specific language, called ΦLOG, to enable biologists to program solutions to phylogenetic inference problems at a very high level of abstraction. The implementation infrastructure (interpreter, compiler, debugger) for the DSL is automatically obtained through a software engineering framework based on Denotational Semantics and Logic Programming.

We present a logic programming based framework for rapidly translating one formal notation Ls to another formal notation Lt. The framework is based on Horn logical semantics-a logic programming encoding of formal semantics. A Horn logical semantics of the language Ls is constructed which employs the parse trees of the language Lt as semantic domains for expressing the meaning of sentences in Ls. This formal semantics, coded in logic programming, immediately yields an executable (reversible) filter. This (reversible) filter is provably correct, as it is generated from the semantic specification. Our approach provides a formal basis for interoperability and is illustrated through five major practical applications: Translating Nemeth Math Braille notation to LATEX, translating HTML to VoiceXML to make web-pages accessible via an audio-browser or a phone, translating ODBC programs/data to OQL (Object Query Language) programs/data, automatically generating validating parsers for XML, and interoperating between various biological software systems developed for phylogenetic inference via the NEXUS data representation language.