A Characterization of Mixed Unit Interval Graphs

We give a complete characterization of mixed unit interval graphs, the intersection graphs of closed, open, and half-open unit intervals of the real line. This is a proper superclass of the well known unit interval graphs. Our result solves a problem posed by Dourado, Le, Protti, Rautenbach and Szwarcfiter (Mixed unit interval graphs, Discrete Math. 312, 3357-3363 (2012)).Comment: 17 pages, referees' comments adde

Preference aggregation theory without acyclicity: The core without majority dissatisfaction

Acyclicity of individual preferences is a minimal assumption in social choice theory. We replace that assumption by the direct assumption that preferences have maximal elements on a fixed agenda. We show that the core of a simple game is nonempty for all profiles of such preferences if and only if the number of alternatives in the agenda is less than the Nakamura number of the game. The same is true if we replace the core by the core without majority dissatisfaction, obtained by deleting from the agenda all the alternatives that are non-maximal for all players in a winning coalition. Unlike the core, the core without majority dissatisfaction depends only on the players' sets of maximal elements and is included in the union of such sets. A result for an extended framework gives another sense in which the core without majority dissatisfaction behaves better than the core.Comment: 27+3 page

iAggregator: Multidimensional Relevance Aggregation Based on a Fuzzy Operator

International audienceRecently, an increasing number of information retrieval studies have triggered a resurgence of interest in redefining the algorithmic estimation of relevance, which implies a shift from topical to multidimensional relevance assessment. A key underlying aspect that emerged when addressing this concept is the aggregation of the relevance assessments related to each of the considered dimensions. The most commonly adopted forms of aggregation are based on classical weighted means and linear combination schemes to address this issue. Although some initiatives were recently proposed, none was concerned with considering the inherent dependencies and interactions existing among the relevance criteria, as is the case in many real-life applications. In this article, we present a new fuzzy-based operator, called iAggregator, for multidimensional relevance aggregation. Its main originality, beyond its ability to model interactions between different relevance criteria, lies in its generalization of many classical aggregation functions. To validate our proposal, we apply our operator within a tweet search task. Experiments using a standard benchmark, namely, Text REtrieval Conference Microblog,1 emphasize the relevance of our contribution when compared with traditional aggregation schemes. In addition, it outperforms state-of-the-art aggregation operators such as the Scoring and the And prioritized operators as well as some representative learning-to-rank algorithms

Mutational analysis of the C-terminal FATC domain of Saccharomyces cerevisiae Tra1

Tra1 is a component of the Saccharomyces cerevisiae SAGA and NuA4 complexes and a member of the PIKK family, which contain a C-terminal phosphatidylinositol 3-kinase-like (PI3K) domain followed by a 35-residue FATC domain. Single residue changes of L3733A and F3744A, within the FATC domain, resulted in transcriptional changes and phenotypes that were similar but not identical to those caused by mutations in the PI3K domain or deletions of other SAGA or NuA4 components. The distinct nature of the FATC mutations was also apparent from the additive effect of tra1-L3733A with SAGA, NuA4, and tra1 PI3K domain mutations. Tra1-L3733A associates with SAGA and NuA4 components and with the Gal4 activation domain, to the same extent as wild-type Tra1; however, steady-state levels of Tra1-L3733A were reduced. We suggest that decreased stability of Tra1-L3733A accounts for the phenotypes since intragenic suppressors of tra1-L3733A restored Tra1 levels, and reducing wild-type Tra1 led to comparable growth defects. Also supporting a key role for the FATC domain in the structure/function of Tra1, addition of a C-terminal glycine residue resulted in decreased association with Spt7 and Esa1, and loss of cellular viability. These findings demonstrate the regulatory potential of mechanisms targeting the FATC domains of PIKK proteins

Effects of Bisphenol-A and Other Endocrine Disruptors Compared With Abnormalities of Schizophrenia: An Endocrine-Disruption Theory of Schizophrenia

In recent years, numerous substances have been identified as so-called “endocrine disruptors” because exposure to them results in disruption of normal endocrine function with possible adverse health outcomes. The pathologic and behavioral abnormalities attributed to exposure to endocrine disruptors like bisphenol-A (BPA) have been studied in animals. Mental conditions ranging from cognitive impairment to autism have been linked to BPA exposure by more than one investigation. Concurrent with these developments in BPA research, schizophrenia research has continued to find evidence of possible endocrine or neuroendocrine involvement in the disease. Sufficient information now exists for a comparison of the neurotoxicological and behavioral pathology associated with exposure to BPA and other endocrine disruptors to the abnormalities observed in schizophrenia. This review summarizes these findings and proposes a theory of endocrine disruption, like that observed from BPA exposure, as a pathway of schizophrenia pathogenesis. The review shows similarities exist between the effects of exposure to BPA and other related chemicals with schizophrenia. These similarities can be observed in 11 broad categories of abnormality: physical development, brain anatomy, cellular anatomy, hormone function, neurotransmitters and receptors, proteins and factors, processes and substances, immunology, sexual development, social behaviors or physiological responses, and other behaviors. Some of these similarities are sexually dimorphic and support theories that sexual dimorphisms may be important to schizophrenia pathogenesis. Research recommendations for further elaboration of the theory are proposed

Discussion of "Probabilistic Index Models," by Thas, O., de Neve, J., Lieven, C. and Ottoy., J.-P.

We present a semiparametric statistical model for the probabilistic index which can be defined as P (Y \u3c-Y*) where Y and Y* are independent random response variables associated with covariate patterns X and X* respectively. A link function defines the relationship between the probabilistic index and a linear predictor. Asymptotic normality of the estimators and consistency of the covariance matrix estimator are established through semiparametric theory. The model is illustrated with several examples, and the estimation theory is validated in a simulation study

sFlt Multivalent Conjugates Inhibit Angiogenesis and Improve Half-Life In Vivo

We would like to thank Jonathan Winger and Xiao Zhu for guidance with the insect cell protein expression system and providing reagents. We would like to acknowledge Ann Fischer for help with expressing the sFlt protein in the Tissue Culture Facility at UC Berkeley and Dawn Spelke and Anusuya Ramasubramanian for help optimizing protein purification from insect cells. We are also grateful for the help from Leah Byrne and John Flannery at in the Helen Wills Neuroscience Institute at UC Berkeley for aiding us in the development of the rat intravitreal residence time model and for allowing us to use their facilities.Current anti-VEGF drugs for patients with diabetic retinopathy suffer from short residence time in the vitreous of the eye. In order to maintain biologically effective doses of drug for inhibiting retinal neovascularization, patients are required to receive regular monthly injections of drug, which often results in low patient compliance and progression of the disease. To improve the intravitreal residence time of anti-VEGF drugs, we have synthesized multivalent bioconjugates of an anti-VEGF protein, soluble fms-like tyrosine kinase-1 (sFlt) that is covalently grafted to chains of hyaluronic acid (HyA), conjugates that are termed mvsFlt. Using a mouse corneal angiogenesis assay, we demonstrate that covalent conjugation to HyA chains does not decrease the bioactivity of sFlt and that mvsFlt is equivalent to sFlt at inhibiting corneal angiogenesis. In a rat vitreous model, we observed that mvsFlt had significantly increased intravitreal residence time compared to the unconjugated sFlt after 2 days. The calculated intravitreal half-lives for sFlt and mvsFlt were 3.3 and 35 hours, respectively. Furthermore, we show that mvsFlt is more effective than the unconjugated form at inhibiting retinal neovascularization in an oxygen-induced retinopathy model, an effect that is most likely due to the longer half-life of mvsFlt in the vitreous. Taken together, our results indicate that conjugation of sFlt to HyA does not affect its affinity for VEGF and this conjugation significantly improves drug half-life. These in vivo results suggest that our strategy of multivalent conjugation could substantially improve upon drug half-life, and thus the efficacy of currently available drugs that are used in diseases such as diabetic retinopathy, thereby improving patient quality of life.Yeshttp://www.plosone.org/static/editorial#pee