247 research outputs found

    Introspection dynamics: a simple model of counterfactual learning in asymmetric games

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    Social behavior in human and animal populations can be studied as an evolutionary process.Individuals often make decisions between different strategies, and those strategies that yield afitness advantage tend to spread. Traditionally, much work in evolutionary game theory considerssymmetric games: individuals are assumed to have access to the same set of strategies, and theyexperience the same payoff consequences. As a result, they can learn more profitable strategies byimitation. However, interactions are oftentimes asymmetric. In that case, imitation may beinfeasible (because individuals differ in the strategies they are able to use), or it may be undesirable(because individuals differ in their incentives to use a strategy). Here, we consider an alternativelearning process which applies to arbitrary asymmetric games,introspection dynamics. Accordingto this dynamics, individuals regularly compare their present strategy to a randomly chosenalternative strategy. If the alternative strategy yields a payoff advantage, it is more likely adopted. Inthis work, we formalize introspection dynamics for pairwise games. We derive simple and explicitformulas for the abundance of each strategy over time and apply these results to severalwell-known social dilemmas. In particular, for the volunteer’s timing dilemma, we show that theplayer with the lowest cooperation cost learns to cooperate without delay

    United States Response to Questionnaire Concerning \u3cem\u3eCollective Management of Rights\u3c/em\u3e

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    ALAI-USA is the U.S. branch of ALAI (Association Littèraire et Artistique Internationale). ALAI-USA was started in the 1980\u27s by the late Professor Melville B. Nimmer, and was later expanded by Professor John M. Kernochan

    Sex or cannibalism: Polyphenism and kin recognition control social action strategies in nematodes

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    Resource polyphenisms, where single genotypes produce alternative feeding strategies in response to changing environments, are thought to be facilitators of evolutionary novelty. However, understanding the interplay between environment, morphology, and behavior and its significance is complex. We explore a radiation of Pristionchus nematodes with discrete polyphenic mouth forms and associated microbivorous versus cannibalistic traits. Notably, comparing 29 Pristionchus species reveals that reproductive mode strongly correlates with mouth-form plasticity. Male-female species exhibit the microbivorous morph and avoid parent-offspring conflict as indicated by genetic hybrids. In contrast, hermaphroditic species display cannibalistic morphs encouraging competition. Testing predation between 36 co-occurring strains of the hermaphrodite P. pacificus showed that killing inversely correlates with genomic relatedness. These empirical data together with theory reveal that polyphenism (plasticity), kin recognition, and relatedness are three major factors that shape cannibalistic behaviors. Thus, developmental plasticity influences cooperative versus competitive social action strategies in diverse animals

    Analysis of Bacterial Stent Colonization: The Role of Urine and Device Microbiological Cultures

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    : In this study, we explored the incidence of double J (JJ) contamination of patients who underwent an endourological procedure for urinary stones and ureteral stenosis. We developed a prospective study between January 2019 and December 2021. Ninety-seven patients, 54 male and 43 female, were enrolled. Urine culture was taken during four steps: before stent insertion, a sample from selective renal pelvis catheterization, a sample two days after the JJ insertion and finally, after the stent removal procedure. At the time of the stent removal, 1 cm of proximal and distal ends were cut off and placed in the culture for bacterial evaluation. Cohen's kappa coefficient value (k) and concordance rates of microbiological culture results were evaluated. The study group comprised 56% of male patients. Proximal and distal stent cultures were positive in 81 and 78 patients. The concordance rate of microbiological cultures between proximal and distal double J stent is 88% (k 0.6). The most common pathogens isolated from urine and stent cultures were Enterococcus spp. in 52 cases and Klebsiella spp. in 27 cases

    Immunomodulation with IL-4Rα antisense oligonucleotide prevents respiratory syncytial virus-mediated pulmonary disease

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    Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Severe RSV infections in infants cause bronchiolitis, wheeze, and/or cough and significantly increase the risk for developing asthma. RSV pathogenesis is thought to be due to a Th2-type immune response initiated in response to RSV infection, specifically in the infant. Using a neonatal mouse system as an appropriate model for human infants, we sought to determine whether local inhibition of IL-4Rα expression during primary RSV infection in the neonate would prevent Th2-skewed responses to secondary RSV infection and improve longterm pulmonary function. To reduce IL-4Rα expression, antisense oligonucleotides (ASOs) specific for IL-4Rα were administered intranasally to neonatal mice at the time of primary infection. Mice were initially infected with RSV at 1 wk of age and were reinfected at 6 wk of age. Administration of IL-4Rα ASOs during primary RSV infection in neonatal mice abolished the pulmonary dysfunction normally observed following reinfection in the adult. This ablation of pulmonary dysfunction correlated with a persistent rebalancing of the Th cell compartment with decreased Th2 responses (i.e., reduced goblet cell hyperplasia, Th2 cells, and cytokine secretion) and increased Th1 responses (i.e., elevated Th1 cell numbers and type I Abs and cytokines). Our data support our hypothesis that a reduction in the Th2 immune response during primary infection in neonates prevents Th2-mediated pulmonary pathology initially and upon reinfection and further suggest that vaccine strategies incorporating IL-4Rα ASOs may be of significant benefit to infants. Copyright © 2010 by The American Association of Immunologists, Inc

    Impact of immigration on burden of Tuberculosis in Umbria: a low-incidence Italian region with high immigrants rates

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    Introduction. In Italy, Tubercolosis (TB) has increasingly become a disease for specific population subgroups such as immi- grants. The objective of this paper is to describe the trend in TB incidence from 1999 to 2008 in Umbria: a low-incidence Italian region with high immigrants rates. Methods. Data were obtained from the Regional Information System for Infectious Diseases. Using a linear regressions model we estimated trends for number of cases and incidence rates; with a logistic regression model we estimated the effect of a set of covariates on the probability of being affected by TB. Result. 590 TB cases were reported of whom 254 (43%) were foreign. In 2008 39.7 new cases per 100.000 were registered among foreign-born subjects. TB incidence among Italians was 3.8/100.000 Italians. But a linear regression analysis showed a statistically significant decreasing trend in the notification rate among foreign-born people (coef: -7.32, r2:0.57, p inf. 0.05). The probability to be affected by extra-pulmonary is significantly larger in foreign patients (OR = 0.72, CI = 0.48-1.07). Foreign unskilled workers report a higher probability to be affected by TB (OR = 19.05, CI = 6.01-60.4). Discussion. Increasing immigration rates may affect TB epide- miology. The analysis of incidence trends is an important tool for monitoring tuberculosis disease control and to identify specific sub-group at risk

    Cystatin B Involvement in Synapse Physiology of Rodent Brains and Human Cerebral Organoids

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    Cystatin B (CSTB) is a ubiquitous protein belonging to a superfamily of protease inhibitors. CSTB may play a critical role in brain physiology because its mutations cause progressive myoclonic epilepsy-1A (EPM1A), the most common form of progressive myoclonic epilepsy. However, the molecular mechanisms underlying the role of CSTB in the central nervous system (CNS) are largely unknown. To investigate the possible involvement of CSTB in the synaptic plasticity, we analyzed its expression in synaptosomes as a model system in studying the physiology of the synaptic regions of the CNS. We found that CSTB is not only present in the synaptosomes isolated from rat and mouse brain cortex, but also secreted into the medium in a depolarization-controlled manner. In addition, using biorthogonal noncanonical amino acid tagging (BONCAT) procedure, we demonstrated, for the first time, that CSTB is locally synthesized in the synaptosomes. The synaptic localization of CSTB was confirmed in a human 3D model of cortical development, namely cerebral organoids. Altogether, these results suggest that CSTB may play a role in the brain plasticity and open a new perspective in studying the involvement of CSTB deregulation in neurodegenerative and neuropsychiatric diseases

    Decomposition of semigroup algebras

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    Let A \subseteq B be cancellative abelian semigroups, and let R be an integral domain. We show that the semigroup ring R[B] can be decomposed, as an R[A]-module, into a direct sum of R[A]-submodules of the quotient ring of R[A]. In the case of a finite extension of positive affine semigroup rings we obtain an algorithm computing the decomposition. When R[A] is a polynomial ring over a field we explain how to compute many ring-theoretic properties of R[B] in terms of this decomposition. In particular we obtain a fast algorithm to compute the Castelnuovo-Mumford regularity of homogeneous semigroup rings. As an application we confirm the Eisenbud-Goto conjecture in a range of new cases. Our algorithms are implemented in the Macaulay2 package MonomialAlgebras.Comment: 12 pages, 2 figures, minor revisions. Package may be downloaded at http://www.math.uni-sb.de/ag/schreyer/jb/Macaulay2/MonomialAlgebras/html

    Evidence of Genetic Instability in Tumors and Normal Nearby Tissues

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    We have analyzed the sequence heterogeneity of the transcripts of the human HPRT and G6PD single copy genes that are not considered tumor markers. Analyses have been performed on different colon cancers and on the nearby histologically normal tissues of two male patients. Several copies of each cDNA, which were produced by cloning the RT-PCR-amplified fragments of the specific mRNA, have been sequenced. Similar analyses have been performed on blood samples of two ostensibly healthy males as reference controls. The sequence heterogeneity of the HPRT and G6PD genes was also determined on DNA from tumor tissues. The employed analytical approach revealed the presence of low-frequency mutations not detectable by other procedures. The results show that genetic heterogeneity is detectable in HPRT and G6PD transcripts in both tumors and nearby healthy tissues of the two studied colon tumors. Similar frequencies of mutations are observed in patient genomic DNA, indicating that mutations have a somatic origin. HPRT transcripts show genetic heterogeneity also in healthy individuals, in agreement with previous results on human T-cells, while G6PD transcript heterogeneity is a characteristic of the patient tissues. Interestingly, data on TP53 show little, if any, heterogeneity in the same tissues. CONCLUSIONS/SIGNIFICANCE: These findings show that genetic heterogeneity is a peculiarity not only of cancer cells but also of the normal tissue where a tumor arises

    Hydroxylation of the NOTCH1 intracellular domain regulates Notch signaling dynamics

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    Notch signaling plays a pivotal role in the development and, when dysregulated, it contributes to tumorigenesis. The amplitude and duration of the Notch response depend on the posttranslational modifications (PTMs) of the activated NOTCH receptor - the NOTCH intracellular domain (NICD). In normoxic conditions, the hydroxylase FIH (factor inhibiting HIF) catalyzes the hydroxylation of two asparagine residues of the NICD. Here, we investigate how Notch-dependent gene transcription is regulated by hypoxia in progenitor T cells. We show that the majority of Notch target genes are downregulated upon hypoxia. Using a hydroxyl-specific NOTCH1 antibody we demonstrate that FIH-mediated NICD1 hydroxylation is reduced upon hypoxia or treatment with the hydroxylase inhibitor dimethyloxalylglycine (DMOG). We find that a hydroxylation-resistant NICD1 mutant is functionally impaired and more ubiquitinated. Interestingly, we also observe that the NICD1-deubiquitinating enzyme USP10 is downregulated upon hypoxia. Moreover, the interaction between the hydroxylation-defective NICD1 mutant and USP10 is significantly reduced compared to the NICD1 wild-type counterpart. Together, our data suggest that FIH hydroxylates NICD1 in normoxic conditions, leading to the recruitment of USP10 and subsequent NICD1 deubiquitination and stabilization. In hypoxia, this regulatory loop is disrupted, causing a dampened Notch response
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