Toward Agent Programs with Circuit Semantics

New ideas are presented for computing and organizing actions for autonomous agents in dynamic environments-environments in which the agent's current situation cannot always be accurately discerned and in which the effects of actions cannot always be reliably predicted. The notion of 'circuit semantics' for programs based on 'teleo-reactive trees' is introduced. Program execution builds a combinational circuit which receives sensory inputs and controls actions. These formalisms embody a high degree of inherent conditionality and thus yield programs that are suitably reactive to their environments. At the same time, the actions computed by the programs are guided by the overall goals of the agent. The paper also speculates about how programs using these ideas could be automatically generated by artificial intelligence planning systems and adapted by learning methods

A software pipeline for processing and identification of fungal ITS sequences

<p>Abstract</p> <p>Background</p> <p>Fungi from environmental samples are typically identified to species level through DNA sequencing of the nuclear ribosomal internal transcribed spacer (<it>ITS</it>) region for use in BLAST-based similarity searches in the International Nucleotide Sequence Databases. These searches are time-consuming and regularly require a significant amount of manual intervention and complementary analyses. We here present software – in the form of an identification pipeline for large sets of fungal <it>ITS </it>sequences – developed to automate the BLAST process and several additional analysis steps. The performance of the pipeline was evaluated on a dataset of 350 <it>ITS </it>sequences from fungi growing as epiphytes on building material.</p> <p>Results</p> <p>The pipeline was written in Perl and uses a local installation of NCBI-BLAST for the similarity searches of the query sequences. The variable subregion <it>ITS2 </it>of the <it>ITS </it>region is extracted from the sequences and used for additional searches of higher sensitivity. Multiple alignments of each query sequence and its closest matches are computed, and query sequences sharing at least 50% of their best matches are clustered to facilitate the evaluation of hypothetically conspecific groups. The pipeline proved to speed up the processing, as well as enhance the resolution, of the evaluation dataset considerably, and the fungi were found to belong chiefly to the <it>Ascomycota</it>, with <it>Penicillium </it>and <it>Aspergillus </it>as the two most common genera. The <it>ITS2 </it>was found to indicate a different taxonomic affiliation than did the complete <it>ITS </it>region for 10% of the query sequences, though this figure is likely to vary with the taxonomic scope of the query sequences.</p> <p>Conclusion</p> <p>The present software readily assigns large sets of fungal query sequences to their respective best matches in the international sequence databases and places them in a larger biological context. The output is highly structured to be easy to process, although it still needs to be inspected and possibly corrected for the impact of the incomplete and sometimes erroneously annotated fungal entries in these databases. The open source pipeline is available for UNIX-type platforms, and updated releases of the target database are made available biweekly. The pipeline is easily modified to operate on other molecular regions and organism groups.</p

Challenging claims in the study of migratory birds and climate change

Recent shifts in phenology in response to climate change are well established but often poorly understood. Many animals integrate climate change across a spatially and temporally dispersed annual life cycle, and effects are modulated by ecological interactions, evolutionary change and endogenous control mechanisms. Here we assess and discuss key statements emerging from the rapidly developing study of changing spring phenology in migratory birds. These well-studied organisms have been instrumental for understanding climate-change effects, but research is developing rapidly and there is a need to attack the big issues rather than risking affirmative science. Although we agree poorly on the support for most claims, agreement regarding the knowledge basis enables consensus regarding broad patterns and likely causes. Empirical data needed for disentangling mechanisms are still scarce, and consequences at a population level and on community composition remain unclear. With increasing knowledge, the overall support (‘consensus view’) for a claim increased and between-researcher variability in support (‘expert opinions') decreased, indicating the importance of assessing and communicating the knowledge basis. A proper integration across biological disciplines seems essential for the field's transition from affirming patterns to understanding mechanisms and making robust predictions regarding future consequences of shifting phenologies

Games as tools to address conservation conflicts

Conservation conflicts represent complex multilayered problems that are challenging to study. We explore the utility of theoretical, experimental, and constructivist approaches to games to help to understand and manage these challenges. We show how these approaches can help to develop theory, understand patterns in conflict, and highlight potentially effective management solutions. The choice of approach should be guided by the research question and by whether the focus is on testing hypotheses, predicting behaviour, or engaging stakeholders. Games provide an exciting opportunity to help to unravel the complexity in conflicts, while researchers need an awareness of the limitations and ethical constraints involved. Given the opportunities, this field will benefit from greater investment and development

Revealing hidden species distribution with pheromones: the case of Synanthedon vespiformis (Lepidoptera: Sesiidae) in Sweden

Synanthedon vespiformis L. (Lepidoptera: Sesiidae) is considered a rare insect in Sweden, discovered in 1860, with only a few observations recorded until a sex pheromone attractant became available recently. This study details a national survey conducted using pheromones as a sampling method for this species. Through pheromone trapping we captured 439 specimens in Southern Sweden at 77 sites, almost tripling the number of previously reported records for this species. The results suggest that S. vespiformis is truly a rare species with a genuinely scattered distribution, but can be locally abundant. Habitat analyses were conducted in order to test the relationship between habitat quality and the number of individuals caught. In Sweden, S. vespiformis is thought to be associated with oak hosts, but our attempts to predict its occurrence by the abundance of oaks yielded no significant relationships. We therefore suggest that sampling bias and limited knowledge on distribution may have led to the assumption that this species is primarily reliant on oaks in the northern part of its range, whereas it may in fact be polyphagous, similar to S. vespiformis found as an agricultural pest in Central and Southern Europe. We conclude that pheromones can massively enhance sampling potential for this and other rare lepidopteran species. Large-scale pheromone-based surveys provide a snapshot of true presences and absences across a considerable part of a species national distribution range, and thus for the first time provide a viable means of systematically assessing changes in distribution over time with high spatiotemporal resolution

Human antimicrobial peptide LL-37 is present in atherosclerotic plaques and induces death of vascular smooth muscle cells: a laboratory study

BACKGROUND: Death of smooth muscle cells in the atherosclerotic plaques makes the plaques more prone to rupture, which can initiate an acute ischemic event. The development of atherosclerosis includes the migration of immune cells e.g. monocytes/macrophages and T lymphocytes into the lesions. Immune cells can release antimicrobial peptides. One of these, human cathelicidin antimicrobial peptide hCAP-18, is cleaved by proteinase 3 generating a 4.5 kDa C-terminal fragment named LL-37, which has been shown to be cytotoxic. The aim of the study was to explore a potential role of LL-37 in the pathophysiology of atherosclerosis. METHODS: We investigated the presence of LL-37 in human atherosclerotic lesions obtained at autopsy using immunohistochemistry. The direct effects of LL-37 on cultured vascular smooth muscle cells and isolated neutrophil granulocytes were investigated with morphological, biochemical and flow cytometry analysis. RESULTS: The neointima of atherosclerotic plaques was found to contain LL-37-like immunoreactivity, mainly in macrophages. In cultured smooth muscle cells, LL-37 at 30 μg/ml caused cell shrinkage, membrane blebbing, nuclear condensation, DNA fragmentation and an increase in caspase-3 activity as studied by microscopy, ELISA and enzyme activity assay, respectively. Flow cytometry demonstrated that LL-37 in a subset of the cells caused a small but rapidly developing increase in membrane permeability to propidium iodide, followed by a gradual development of FITC-annexin V binding. Another cell population stained heavily with both propidium iodide and FITC-annexin V. Neutrophil granulocytes were resistant to these effects of LL-37. CONCLUSION: This study shows that LL-37 is present in atherosclerotic lesions and that it induces death of vascular smooth muscle cells. In a subset of cells, the changes indicate the development of apoptosis triggered by an initial mild perturbation of plasma membrane integrity. The findings suggest a role for LL-37 as a mediator of immune cell-induced death of vascular smooth muscle cells in atherosclerosis

Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder

Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex ligation-dependent probe amplification. Mutations in the SLC2A1 gene were detected in 54 patients (41%) and subsequently in three clinically affected family members. In these 57 patients we identified 49 different mutations, including six multiple exon deletions, six known mutations and 37 novel mutations (13 missense, five nonsense, 13 frame shift, four splice site and two translation initiation mutations). Clinical data were retrospectively collected from referring physicians by means of a questionnaire. Three different phenotypes were recognized: (i) the classical phenotype (84%), subdivided into early-onset (<2 years) (65%) and late-onset (18%); (ii) a non-classical phenotype, with mental retardation and movement disorder, without epilepsy (15%); and (iii) one adult case of glucose transporter-1 deficiency syndrome with minimal symptoms. Recognizing glucose transporter-1 deficiency syndrome is important, since a ketogenic diet was effective in most of the patients with epilepsy (86%) and also reduced movement disorders in 48% of the patients with a classical phenotype and 71% of the patients with a non-classical phenotype. The average delay in diagnosing classical glucose transporter-1 deficiency syndrome was 6.6 years (range 1 month-16 years). Cerebrospinal fluid glucose was below 2.5 mmol/l (range 0.9-2.4 mmol/l) in all patients and cerebrospinal fluid : blood glucose ratio was below 0.50 in all but one patient (range 0.19-0.52). Cerebrospinal fluid lactate was low to normal in all patients. Our relatively large series of 57 patients with glucose transporter-1 deficiency syndrome allowed us to identify correlations between genotype, phenotype and biochemical data. Type of mutation was related to the severity of mental retardation and the presence of complex movement disorders. Cerebrospinal fluid : blood glucose ratio was related to type of mutation and phenotype. In conclusion, a substantial number of the patients with glucose transporter-1 deficiency syndrome do not have epilepsy. Our study demonstrates that a lumbar puncture provides the diagnostic clue to glucose transporter-1 deficiency syndrome and can thereby dramatically reduce diagnostic delay to allow early start of the ketogenic die

Multi-capillary column-ion mobility spectrometry (MCC-IMS) as a new method for the quantification of occupational exposure to sevoflurane in anaesthesia workplaces: an observational feasibility study

BACKGROUND: Occupational exposure to sevoflurane has the potential to cause health damage in hospital personnel. Workplace contamination with the substance mostly is assessed by using photoacoustic infrared spectrometry with detection limits of 10 ppbv. Multi-capillary column-ion mobility spectrometry (MCC-IMS) could be an alternative technology for the quantification of sevoflurane in the room air and could be even more accurate because of potentially lower detection limits. The aim of this study was to test the hypothesis that MCC-IMS is able to detect and monitor very low concentrations of sevoflurane (<10 ppbv) and to evaluate the exposure of hospital personnel to sevoflurane during paediatric anaesthesia and in the post anaesthesia care unit (PACU). METHODS: A MCC-IMS device was calibrated to several concentrations of sevoflurane and limits of detection (LOD) and quantification (LOQ) were calculated. Sevoflurane exposure of hospital personnel was measured at two anaesthesia workplaces and time-weighted average (TWA) values were calculated. RESULTS: The LOD was 0.0068 ppbv and the LOQ was 0.0189 ppbv. During paediatric anaesthesia the mean sevoflurane concentration was 46.9 ppbv (8.0 - 314.7 ppbv) with TWA values between 5.8 and 45.7 ppbv. In the PACU the mean sevoflurane concentration was 27.9 ppbv (8.0 – 170.2 ppbv) and TWA values reached from 8.3 to 45.1 ppbv. CONCLUSIONS: MCC-IMS shows a significantly lower LOD and LOQ than comparable methods. It is a reliable technology for monitoring sevoflurane concentrations at anaesthesia workplaces and has a particular strength in quantifying low-level contaminations of sevoflurane. The exposure of the personnel working in these areas did not exceed recommended limits and therefore adverse health effects are unlikely

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups