Ermakov's Superintegrable Toy and Nonlocal Symmetries

We investigate the symmetry properties of a pair of Ermakov equations. The system is superintegrable and yet possesses only three Lie point symmetries with the algebra sl(2,R). The number of point symmetries is insufficient and the algebra unsuitable for the complete specification of the system. We use the method of reduction of order to reduce the nonlinear fourth-order system to a third-order system comprising a linear second-order equation and a conservation law. We obtain the representation of the complete symmetry group from this system. Four of the required symmetries are nonlocal and the algebra is the direct sum of a one-dimensional Abelian algebra with the semidirect sum of a two-dimensional solvable algebra with a two-dimensional Abelian algebra. The problem illustrates the difficulties which can arise in very elementary systems. Our treatment demonstrates the existence of possible routes to overcome these problems in a systematic fashion.Comment: Published in SIGMA (Symmetry, Integrability and Geometry: Methods and Applications) at http://www.emis.de/journals/SIGMA

Analytic Behaviour of Competition among Three Species

We analyse the classical model of competition between three species studied by May and Leonard ({\it SIAM J Appl Math} \textbf{29} (1975) 243-256) with the approaches of singularity analysis and symmetry analysis to identify values of the parameters for which the system is integrable. We observe some striking relations between critical values arising from the approach of dynamical systems and the singularity and symmetry analyses.Comment: 14 pages, to appear in Journal of Nonlinear Mathematical Physic

Exploring inter-organizational paradoxes: Methodological lessons from a study of a grand challenge

In this paper we outline a methodological framework for studying the inter-organizational aspects of paradoxes and specify this in relation to grand challenges. Grand challenges are large-scale, complex, enduring problems that affect large populations, have a strong social component, and appear intractable. Our methodological insights draw from our study of the insurance protection gap, a grand challenge that arises when economic losses from largescale disaster significantly exceed the insured loss, leading to economic and social hardship for the affected communities. We provide insights into collecting data to uncover the paradoxical elements inherent in grand challenges and then propose three analytical techniques for studying inter-organizational paradoxes: zooming in and out, tracking problematization, and tracking boundaries and boundary organizations. These techniques can be used to identify and follow how contradictions and interdependences emerge and dynamically persist within inter-organizational interactions and how these shape and are shaped by the unfolding dynamics of the grand challenge. Our techniques and associated research design help advance paradox theorizing by moving it to the inter-organizational and systemic level. This paper also illustrates paradox as a powerful lens through which to further our understanding of grand challenges

An algebraic approach to laying a ghost to rest

In the recent literature there has been a resurgence of interest in the fourth-order field-theoretic model of Pais-Uhlenbeck \cite {Pais-Uhlenbeck 50 a}, which has not had a good reception over the last half century due to the existence of {\em ghosts} in the properties of the quantum mechanical solution. Bender and Mannheim \cite{Bender 08 a} were successful in persuading the corresponding quantum operator to `give up the ghost'. Their success had the advantage of making the model of Pais-Uhlenbeck acceptable to the physical community and in the process added further credit to the cause of advancement of the use of ${\cal PT}$ symmetry. We present a case for the acceptance of the Pais-Uhlenbeck model in the context of Dirac's theory by providing an Hamiltonian which is not quantum mechanically haunted. The essential point is the manner in which a fourth-order equation is rendered into a system of second-order equations. We show by means of the method of reduction of order \cite {Nucci} that it is possible to construct an Hamiltonian which gives rise to a satisfactory quantal description without having to abandon Dirac.Comment: 8 page

Unusual cardiovascular complications of brucellosis presenting in two men: two case reports and a review of the literature

Introduction: Brucellosis is a zoonosis with worldwide distribution, which is particularly endemic in many countries of the Mediterranean basin. Cardiovascular complications of this disease, such as endocarditis, myocarditis and pericarditis, are very rare, with even fewer cases of myocarditis or asymptomatic pericardial effusion in the absence of concomitant endocarditis being reported. Case presentation: We report two cases of brucellosis in two Caucasian men, aged 17 and 34 years old, with myocarditis and asymptomatic pericardial effusion, respectively. Of note, neither patient had concomitant endocarditis. The disease was confirmed serologically and by blood cultures. Both patients recovered completely after receiving appropriate antibiotic treatment without any sign of relapse during a follow-up of 12 months. Conclusion: These two cases emphasize that in endemic areas Brucella can be considered as a potentially causative agent of idiopathic pericardial effusion or myocarditis, even in the absence of concomitant endocarditis. This possibility could be taken into account particularly in cases where contraction of brucellosis is possible, such as occupational exposure or consumption of unpasteurized dairy products. © 2011 Gatselis et al; licensee BioMed Central Ltd

Evidence for a lack of a direct transcriptional suppression of the iron regulatory peptide hepcidin by hypoxia-inducible factors.

BACKGROUND: Hepcidin is a major regulator of iron metabolism and plays a key role in anemia of chronic disease, reducing intestinal iron uptake and release from body iron stores. Hypoxia and chemical stabilizers of the hypoxia-inducible transcription factor (HIF) have been shown to suppress hepcidin expression. We therefore investigated the role of HIF in hepcidin regulation. METHODOLOGY/PRINCIPAL FINDINGS: Hepcidin mRNA was down-regulated in hepatoma cells by chemical HIF stabilizers and iron chelators, respectively. In contrast, the response to hypoxia was variable. The decrease in hepcidin mRNA was not reversed by HIF-1alpha or HIF-2alpha knock-down or by depletion of the HIF and iron regulatory protein (IRP) target transferrin receptor 1 (TfR1). However, the response of hepcidin to hypoxia and chemical HIF inducers paralleled the regulation of transferrin receptor 2 (TfR2), one of the genes critical to hepcidin expression. Hepcidin expression was also markedly and rapidly decreased by serum deprivation, independent of transferrin-bound iron, and by the phosphatidylinositol 3 (PI3) kinase inhibitor LY294002, indicating that growth factors are required for hepcidin expression in vitro. Hepcidin promoter constructs mirrored the response of mRNA levels to interleukin-6 and bone morphogenetic proteins, but not consistently to hypoxia or HIF stabilizers, and deletion of the putative HIF binding motifs did not alter the response to different hypoxic stimuli. In mice exposed to carbon monoxide, hypoxia or the chemical HIF inducer N-oxalylglycine, liver hepcidin 1 mRNA was elevated rather than decreased. CONCLUSIONS/SIGNIFICANCE: Taken together, these data indicate that hepcidin is neither a direct target of HIF, nor indirectly regulated by HIF through induction of TfR1 expression. Hepcidin mRNA expression in vitro is highly sensitive to the presence of serum factors and PI3 kinase inhibition and parallels TfR2 expression

NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway

The cilia-associated protein NPHP4 is a negative regulator of Hippo signaling that modulates cell proliferation in mammals

Investigation of tumor hypoxia using a two-enzyme system for in vitro generation of oxygen deficiency

<p>Abstract</p> <p>Background</p> <p>Oxygen deficiency in tumor tissue is associated with a malign phenotype, characterized by high invasiveness, increased metastatic potential and poor prognosis. Hypoxia chambers are the established standard model for <it>in vitro </it>studies on tumor hypoxia. An enzymatic hypoxia system (GOX/CAT) based on the use of glucose oxidase (GOX) and catalase (CAT) that allows induction of stable hypoxia for <it>in vitro </it>approaches more rapidly and with less operating expense has been introduced recently. Aim of this work is to compare the enzymatic system with the established technique of hypoxia chamber in respect of gene expression, glucose metabolism and radioresistance, prior to its application for <it>in vitro </it>investigation of oxygen deficiency.</p> <p>Methods</p> <p>Human head and neck squamous cell carcinoma HNO97 cells were incubated under normoxic and hypoxic conditions using both hypoxia chamber and the enzymatic model. Gene expression was investigated using Agilent microarray chips and real time PCR analysis. ¹⁴C-fluoro-deoxy-glucose uptake experiments were performed in order to evaluate cellular metabolism. Cell proliferation after photon irradiation was investigated for evaluation of radioresistance under normoxia and hypoxia using both a hypoxia chamber and the enzymatic system.</p> <p>Results</p> <p>The microarray analysis revealed a similar trend in the expression of known HIF-1 target genes between the two hypoxia systems for HNO97 cells. Quantitative RT-PCR demonstrated different kinetic patterns in the expression of carbonic anhydrase IX and lysyl oxidase, which might be due to the faster induction of hypoxia by the enzymatic system. ¹⁴C-fluoro-deoxy-glucose uptake assays showed a higher glucose metabolism under hypoxic conditions, especially for the enzymatic system. Proliferation experiments after photon irradiation revealed increased survival rates for the enzymatic model compared to hypoxia chamber and normoxia, indicating enhanced resistance to irradiation. While the GOX/CAT system allows independent investigation of hypoxia and oxidative stress, care must be taken to prevent acidification during longer incubation.</p> <p>Conclusion</p> <p>The results of our study indicate that the enzymatic model can find application for <it>in vitro </it>investigation of tumor hypoxia, despite limitations that need to be considered in the experimental design.</p

Genome-Wide Association Study Identifies Genetic Loci Associated with Iron Deficiency

The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS) was performed using DNA collected from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤ 12 µg/L (cases) and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women). Regression analysis was used to examine the association between case-control status (336 cases, 343 controls) and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP) genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA) medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF) gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10−7 for all). An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P = 7.0×10−9, corrected P = 0.012) was replicated within the VA samples (observed P = 0.012). Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification