Primitive Words, Free Factors and Measure Preservation

Let F_k be the free group on k generators. A word w \in F_k is called primitive if it belongs to some basis of F_k. We investigate two criteria for primitivity, and consider more generally, subgroups of F_k which are free factors. The first criterion is graph-theoretic and uses Stallings core graphs: given subgroups of finite rank H \le J \le F_k we present a simple procedure to determine whether H is a free factor of J. This yields, in particular, a procedure to determine whether a given element in F_k is primitive. Again let w \in F_k and consider the word map w:G x G x ... x G \to G (from the direct product of k copies of G to G), where G is an arbitrary finite group. We call w measure preserving if given uniform measure on G x G x ... x G, w induces uniform measure on G (for every finite G). This is the second criterion we investigate: it is not hard to see that primitivity implies measure preservation and it was conjectured that the two properties are equivalent. Our combinatorial approach to primitivity allows us to make progress on this problem and in particular prove the conjecture for k=2. It was asked whether the primitive elements of F_k form a closed set in the profinite topology of free groups. Our results provide a positive answer for F_2.Comment: This is a unified version of two manuscripts: "On Primitive words I: A New Algorithm", and "On Primitive Words II: Measure Preservation". 42 pages, 14 figures. Some parts of the paper reorganized towards publication in the Israel J. of Mat

miR-126 Is Downregulated in Cystic Fibrosis Airway Epithelial Cells and Regulates TOM1 Expression.

Cystic fibrosis (CF) is one of the most common lethal genetic diseases in which the role of microRNAs has yet to be explored. Predicted to be regulated by miR-126, TOM1 (target of Myb1) has been shown to interact with Toll-interacting protein, forming a complex to regulate endosomal trafficking of ubiquitinated proteins. TOM1 has also been proposed as a negative regulator of IL-1beta and TNF-alpha-induced signaling pathways. MiR-126 is highly expressed in the lung, and we now show for the first time differential expression of miR-126 in CF versus non-CF airway epithelial cells both in vitro and in vivo. MiR-126 downregulation in CF bronchial epithelial cells correlated with a significant upregulation of TOM1 mRNA, both in vitro and in vivo when compared with their non-CF counterparts. Introduction of synthetic pre-miR-126 inhibited luciferase activity in a reporter system containing the full length 3\u27-untranslated region of TOM1 and resulted in decreased TOM1 protein production in CF bronchial epithelial cells. Following stimulation with LPS or IL-1beta, overexpression of TOM1 was found to downregulate NF-kappaB luciferase activity. Conversely, TOM1 knockdown resulted in a significant increase in NF-kappaB regulated IL-8 secretion. These data show that miR-126 is differentially regulated in CF versus non-CF airway epithelial cells and that TOM1 is a miR-126 target that may have an important role in regulating innate immune responses in the CF lung. To our knowledge, this study is the first to report of a role for TOM1 in the TLR2/4 signaling pathways and the first to describe microRNA involvement in CF

Socioeconomic differentials in the immediate mortality effects of the national Irish smoking ban

This article has been made available through the Brunel Open Access Publishing Fund.Background: Consistent evidence has demonstrated that smoking ban policies save lives, but impacts on health inequalities are uncertain as few studies have assessed post-ban effects by socioeconomic status (SES) and findings have been inconsistent. The aim of this study was to assess the effects of the national Irish smoking ban on ischemic heart disease (IHD), stroke, and chronic obstructive pulmonary disease (COPD) mortality by discrete and composite SES indicators to determine impacts on inequalities. Methods: Census data were used to assign frequencies of structural and material SES indicators to 34 local authorities across Ireland with a 2000–2010 study period. Discrete indicators were jointly analysed through principal component analysis to generate a composite index, with sensitivity analyses conducted by varying the included indicators. Poisson regression with interrupted time-series analysis was conducted to examine monthly age and gender-standardised mortality rates in the Irish population, ages ≥35 years, stratified by tertiles of SES indicators. All models were adjusted for time trend, season, influenza, and smoking prevalence. Results: Post-ban mortality reductions by structural SES indicators were concentrated in the most deprived tertile for all causes of death, while reductions by material SES indicators were more equitable across SES tertiles. The composite indices mirrored the results of the discrete indicators, demonstrating that post-ban mortality decreases were either greater or similar in the most deprived when compared to the least deprived for all causes of death. Conclusions: Overall findings indicated that the national Irish smoking ban reduced inequalities in smoking-related mortality. Due to the higher rates of smoking-related mortality in the most deprived group, even equitable reductions across SES tertiles resulted in decreases in inequalities. The choice of SES indicator was influential in the measurement of effects, underscoring that a differentiated analytical approach aided in understanding the complexities in which structural and material factors influence mortality

Chronic hypothermia and energy expenditure in a neurodevelopmentally disabled patient: a case study

Hypothermia is defined as a core body temperature of \u3c35°C and results in a decrease in measured resting energy expenditure. A 51-year-old mentally disabled patient experienced chronic hypothermia from neurologic sequelae. Because of her continued weight gain and increased body fat in the presence of presumed hypocaloric nutrition, indirect calorimetry measurements were performed twice in a 3-month period. The resting energy expenditure measurements prompted a reduction of her daily caloric intake to prevent further overfeeding. Hypothermia reduces oxygen consumption and, as a consequence, decreases resting energy expenditure. In patients for whom chronic hypothermia is a problem, nutritional intake must be adjusted to prevent overfeeding, excessive weight gain, and the long-term complications of an excess of total calories

MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma

<p>ABSTRACT</p> <p>Background</p> <p>Neuroblastoma is a paediatric cancer which originates from precursor cells of the sympathetic nervous system and accounts for 15% of childhood cancer mortalities. With regards to the role of miRNAs in neuroblastoma, miR-34a, mapping to a chromosome 1p36 region that is commonly deleted, has been found to act as a tumor suppressor through targeting of numerous genes associated with cell proliferation and apoptosis.</p> <p>Methods</p> <p>A synthetic miR-34a (or negative control) precursor molecule was transfected into NB1691^lucand SK-N-AS^lucneuroblastoma cells. Quantitative PCR was used to verify increased miR-34a levels in NB1691^lucand SK-N-AS^luccell lines prior to <it>in vitro </it>and <it>in vivo </it>analysis. <it>In vitro </it>analysis of the effects of miR-34a over expression on cell growth, cell cycle and phosphoprotein activation in signal transduction pathways was performed. Neuroblastoma cells over expressing miR-34a were injected retroperitoneally into immunocompromised CB17-SCID mice and tumor burden was assessed over a 21 day period by measuring bioluminescence (photons/sec/cm²).</p> <p>Results</p> <p>Over expression of miR-34a in both NB1691^lucand SK-N-AS^lucneuroblastoma cell lines led to a significant decrease in cell number relative to premiR-negative control treated cells over a 72 hour period. Flow cytometry results indicated that miR-34a induced cell cycle arrest and subsequent apoptosis activation. Phosphoprotein analysis highlighted key elements involved in signal transduction, whose activation was dysregulated as a result of miR-34a introduction into cells. As a potential mechanism of miR-34a action on phosphoprotein levels, we demonstrate that miR-34a over-expression results in a significant reduction of <it>MAP3K9 </it>mRNA and protein levels. Although <it>MAP3K9 </it>is a predicted target of miR-34a, direct targeting could not be validated with luciferase reporter assays. Despite this fact, any functional effects of reduced MAP3K9 expression as a result of miR-34a would be expected to be similar regardless of the mechanism involved. Most notably, <it>in vivo </it>studies showed that tumor growth was significantly repressed after exogenous miR-34a administration in retroperitoneal neuroblastoma tumors.</p> <p>Conclusion</p> <p>We demonstrate for the first time that miR-34a significantly reduces tumor growth in an <it>in vivo </it>orthotopic murine model of neuroblastoma and identified novel effects that miR-34a has on phospho-activation of key proteins involved with apoptosis.</p

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Making a Step Forward Towards Urban Resilience. The Contribution of Digital Innovation

Starting from 'wicked problem' theory as the landmark for framing disaster events in terms of policy issue for city governments, this paper highlights the contribution provided by Big Data analytics and digital innovation in dealing with disaster risks. The research aims at answering the following question: what is the role that 'smart technologies' play in strengthening urban resilience to disaster risks

Geodesic rewriting systems and pregroups

In this paper we study rewriting systems for groups and monoids, focusing on situations where finite convergent systems may be difficult to find or do not exist. We consider systems which have no length increasing rules and are confluent and then systems in which the length reducing rules lead to geodesics. Combining these properties we arrive at our main object of study which we call geodesically perfect rewriting systems. We show that these are well-behaved and convenient to use, and give several examples of classes of groups for which they can be constructed from natural presentations. We describe a Knuth-Bendix completion process to construct such systems, show how they may be found with the help of Stallings' pregroups and conversely may be used to construct such pregroups.Comment: 44 pages, to appear in "Combinatorial and Geometric Group Theory, Dortmund and Carleton Conferences". Series: Trends in Mathematics. Bogopolski, O.; Bumagin, I.; Kharlampovich, O.; Ventura, E. (Eds.) 2009, Approx. 350 p., Hardcover. ISBN: 978-3-7643-9910-8 Birkhause

Effects of Marine Reserves versus Nursery Habitat Availability on Structure of Reef Fish Communities

No-take marine fishery reserves sustain commercial stocks by acting as buffers against overexploitation and enhancing fishery catches in adjacent areas through spillover. Likewise, nursery habitats such as mangroves enhance populations of some species in adjacent habitats. However, there is lack of understanding of the magnitude of stock enhancement and the effects on community structure when both protection from fishing and access to nurseries concurrently act as drivers of fish population dynamics. In this study we test the separate as well as interactive effects of marine reserves and nursery habitat proximity on structure and abundance of coral reef fish communities. Reserves had no effect on fish community composition, while proximity to nursery habitat only had a significant effect on community structure of species that use mangroves or seagrass beds as nurseries. In terms of reef fish biomass, proximity to nursery habitat by far outweighed (biomass 249% higher than that in areas with no nursery access) the effects of protection from fishing in reserves (biomass 21% lower than non-reserve areas) for small nursery fish (≤25 cm total length). For large-bodied individuals of nursery species (>25 cm total length), an additive effect was present for these two factors, although fish benefited more from fishing protection (203% higher biomass) than from proximity to nurseries (139% higher). The magnitude of elevated biomass for small fish on coral reefs due to proximity to nurseries was such that nursery habitats seem able to overrule the usually positive effects on fish biomass by reef reserves. As a result, conservation of nursery habitats gains importance and more consideration should be given to the ecological processes that occur along nursery-reef boundaries that connect neighboring ecosystems

“Cloning” in academe: Mentorship and academic careers

Mentor professors were surveyed with respect to their most successful “protégés” regarding scholarly production, the mentorship role, and their careers. Career stage, network stratification, and weak-tie theories provided the conceptual frameworks. The 62 mentors were highly productive professors who were predominantly both graduates and employees of research universities. Mentors overwhelmingly nominated as their most successful protégés those whose careers were essentially identical to their own—i.e., their “clones.” Women mentors named as most successfully protégés more than twice as many females and males than men did. More productive mentors linked with a greater number of protégés but were less knowledgable about their personal lives, as Granovetter's theory would predict. The results also demonstrate the openness of the network within stratified levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43588/1/11162_2004_Article_BF00973512.pd