Comparative Genomics of a Parthenogenesis-Inducing Wolbachia Symbiont.

Wolbachia is an intracellular symbiont of invertebrates responsible for inducing a wide variety of phenotypes in its host. These host-Wolbachia relationships span the continuum from reproductive parasitism to obligate mutualism, and provide a unique system to study genomic changes associated with the evolution of symbiosis. We present the genome sequence from a parthenogenesis-inducing Wolbachia strain (wTpre) infecting the minute parasitoid wasp Trichogramma pretiosum The wTpre genome is the most complete parthenogenesis-inducing Wolbachia genome available to date. We used comparative genomics across 16 Wolbachia strains, representing five supergroups, to identify a core Wolbachia genome of 496 sets of orthologous genes. Only 14 of these sets are unique to Wolbachia when compared to other bacteria from the Rickettsiales. We show that the B supergroup of Wolbachia, of which wTpre is a member, contains a significantly higher number of ankyrin repeat-containing genes than other supergroups. In the wTpre genome, there is evidence for truncation of the protein coding sequences in 20% of ORFs, mostly as a result of frameshift mutations. The wTpre strain represents a conversion from cytoplasmic incompatibility to a parthenogenesis-inducing lifestyle, and is required for reproduction in the Trichogramma host it infects. We hypothesize that the large number of coding frame truncations has accompanied the change in reproductive mode of the wTpre strain

Constrained interval type-2 fuzzy sets

In many contexts, type-2 fuzzy sets are obtained from a type-1 fuzzy set to which we wish to add uncertainty. However, in the current type-2 representation there is no restriction on the shape of the footprint of uncertainty and the embedded sets that can be considered acceptable. This leads, usually, to the loss of the semantic relationship between the type-2 fuzzy set and the concept it models. As a consequence, the interpretability of some of the embedded sets and the explainability of the uncertainty measures obtained from them can decrease. To overcome these issues, constrained type-2 fuzzy sets have been proposed. However, no formal definitions for some of their key components (e.g. acceptable embedded sets) and constrained operations have been given. The goal of this paper is to provide some theoretical underpinning for the definition of constrained type-2 sets, their inferencing and defuzzification method. To conclude, the constrained inference framework is presented, applied to two real world cases and briefly compared to the standard interval type-2 inference and defuzzification method

Rebuttal to “(2786) Proposal to change the conserved type of Ipomoea, nom. cons. (Convolvulaceae)”

A rebuttal to the proposal to change the conserved type of Ipomoea is presented. We argue the proposal is unnecessary and has no basis in evidence or precedent that justifies its approval

Alpha-level aggregation: A practical approach to type-1 OWA operation for aggregating uncertain information with applications to breast cancer treatments

Type-1 Ordered Weighted Averaging (OWA) operator provides us with a new technique for directly aggregating uncertain information with uncertain weights via OWA mechanism in soft decision making and data mining, in which uncertain objects are modeled by fuzzy sets. The Direct Approach to performing type-1 OWA operation involves high computational overhead. In this paper, we define a type-1 OWA operator based on the α-cuts of fuzzy sets. Then, we prove a Representation Theorem of type-1 OWA operators, by which type-1 OWA operators can be decomposed into a series of α-level type-1 OWA operators. Furthermore, we suggest a fast approach, called Alpha-Level Approach, to implementing the type-1 OWA operator. A practical application of type-1 OWA operators to breast cancer treatments is addressed. Experimental results and theoretical analyses show that: 1) the Alpha-Level Approach with linear order complexity can achieve much higher computing efficiency in performing type-1 OWA operation than the existing Direct Approach, 2) the type-1 OWA operators exhibit different aggregation behaviors from the existing fuzzy weighted averaging (FWA) operators, and 3) the type-1 OWA operators demonstrate the ability to efficiently aggregate uncertain information with uncertain weights in solving real-world soft decision-making problems. © 2011 IEEE

Patterns of bruising in preschool children with inherited bleeding disorders: a longitudinal study

Objective The extent that inherited bleeding disorders affect; number, size and location of bruises in young children <6 years. Design Prospective, longitudinal, observational study. Setting Community. Patients 105 children with bleeding disorders, were compared with 328 without a bleeding disorder and classified by mobility: premobile (non-rolling/rolling over/ sitting), early mobile (crawling/cruising) and walking and by disease severity: severe bleeding disorder factor VIII/IX/XI <1 IU/dL or type 3 von Willebrand disease. Interventions Number, size and location of bruises recorded in each child weekly for up to 12 weeks. Outcomes The interventions were compared between children with severe and mild/moderate bleeding disorders and those without bleeding disorders. Multiple collections for individual children were analysed by multilevel modelling. Results Children with bleeding disorders had more and larger bruises, especially when premobile. Compared with premobile children without a bleeding disorder; the modelled ratio of means (95% CI) for number of bruises/ collection was 31.82 (8.39 to 65.42) for severe bleeding disorders and 5.15 (1.23 to 11.17) for mild/moderate, and was 1.81 (1.13 to 2.23) for size of bruises. Children with bleeding disorders rarely had bruises on the ears, neck, cheeks, eyes or genitalia. Conclusions Children with bleeding disorder have more and larger bruises at all developmental stages. The differences were greatest in premobile children. In this age group for children with unexplained bruising, it is essential that coagulation studies are done early to avoid the erroneous diagnosis of physical abuse when the child actually has a serious bleeding disorder, however a blood test compatible with a mild/moderate bleeding disorder cannot be assumed to be the cause of bruising

Model-Informed Risk Assessment and Decision Making for an Emerging Infectious Disease in the Asia-Pacific Region

Background: Effective response to emerging infectious disease (EID) threats relies on health care systems that can detect and contain localised outbreaks before they reach a national or international scale. The Asia-Pacific region contains low and middle income countries in which the risk of EID outbreaks is elevated and whose health care systems may require international support to effectively detect and respond to such events. The absence of comprehensive data on populations, health care systems and disease characteristics in this region makes risk assessment and decisions about the provision of such support challenging.\ud \ud Methodology/principal findings: We describe a mathematical modelling framework that can inform this process by integrating available data sources, systematically explore the effects of uncertainty, and provide estimates of outbreak risk under a range of intervention scenarios. We illustrate the use of this framework in the context of a potential importation of Ebola Virus Disease into the Asia-Pacific region. Results suggest that, across a wide range of plausible scenarios, preemptive interventions supporting the timely detection of early cases provide substantially greater reductions in the probability of large outbreaks than interventions that support health care system capacity after an outbreak has commenced.\ud \ud Conclusions/significance: Our study demonstrates how, in the presence of substantial uncertainty about health care system infrastructure and other relevant aspects of disease control, mathematical models can be used to assess the constraints that limited resources place upon the ability of local health care systems to detect and respond to EID outbreaks in a timely and effective fashion. Our framework can help evaluate the relative impact of these constraints to identify resourcing priorities for health care system support, in order to inform principled and quantifiable decision making

Generation and Characterization of Mice Carrying a Conditional Allele of the Wwox Tumor Suppressor Gene

WWOX, the gene that spans the second most common human chromosomal fragile site, FRA16D, is inactivated in multiple human cancers and behaves as a suppressor of tumor growth. Since we are interested in understanding WWOX function in both normal and cancer tissues we generated mice harboring a conditional Wwox allele by flanking Exon 1 of the Wwox gene with LoxP sites. Wwox knockout (KO) mice were developed by breeding with transgenic mice carrying the Cre-recombinase gene under the control of the adenovirus EIIA promoter. We found that Wwox KO mice suffered from severe metabolic defect(s) resulting in growth retardation and all mice died by 3 wk of age. All Wwox KO mice displayed significant hypocapnia suggesting a state of metabolic acidosis. This finding and the known high expression of Wwox in kidney tubules suggest a role for Wwox in acid/base balance. Importantly, Wwox KO mice displayed histopathological and hematological signs of impaired hematopoeisis, leukopenia, and splenic atrophy. Impaired hematopoeisis can also be a contributing factor to metabolic acidosis and death. Hypoglycemia and hypocalcemia was also observed affecting the KO mice. In addition, bone metabolic defects were evident in Wwox KO mice. Bones were smaller and thinner having reduced bone volume as a consequence of a defect in mineralization. No evidence of spontaneous neoplasia was observed in Wwox KO mice. We have generated a new mouse model to inactivate the Wwox tumor suppressor gene conditionally. This will greatly facilitate the functional analysis of Wwox in adult mice and will allow investigating neoplastic transformation in specific target tissues