3,654 research outputs found
The 2D/3D dynamics of wall-bounded low-Rm magnetohydrodynamic (MHD) turbulence
No full textWith this experimental study, we give evidence that the dynamics of low-Rm MHD turbulence depends on the diffusion length l_z, which corresponds to the distance over which the Lorentz force is able to diffuse momentum before it is balanced by inertia
A non-synonymous coding change in the CYP19A1 gene Arg264Cys (rs700519) does not affect circulating estradiol, bone structure or fracture
No full textBackground
The biosynthesis of estrogens from androgens is catalyzed by aromatase P450 enzyme, coded by the CYP19A1 gene on chromosome 15q21.2. Genetic variation within the CYP19A1 gene sequence has been shown to alter the function of the enzyme. The aim of this study is to investigate whether a non-synonymous Arg264Cys (rs700519) single nucleotide polymorphism (SNP) is associated with altered levels of circulating estradiol, areal bone mineral density or fracture.
Methods
This population- based study of 1,022 elderly Caucasian women (mean age 74.95 ± 2.60 years) was genotyped for the rs700519 SNP were analyzed to detect any association with endocrine and bone phenotypes.
Results
The genotype frequencies were 997 wildtype (97.6%), 24 heterozygous (2.3%) and 1 homozygous (0.1%). When individuals were grouped by genotype, there was no association between the polymorphism and serum estradiol (wildtype 27.5 ± 16.0; variants 31.2 ± 18.4, P = 0.27). There was also no association seen on hip bone mineral density (wildtype 0.81 ± 0.12; 0.84 ± 0.14 for variants, P = 0.48) or femoral neck bone mineral density (0.69 ± 0.10 for wildtype; 0.70 ± 0.12 for variants, P = 0.54) before or after correction of the data with age, height, weight and calcium therapy. There were also no associations with quantitative ultrasound measures of bone structure (broadband ultrasound attenuation, speed of sound and average stiffness).
Conclusions
In a cohort of 1,022 elderly Western Australian women, the presence of Arg264Cys (rs700519) polymorphism was not found to be associated with serum estradiol, bone structure or phenotypes
Triangular Constellations in Flows
No full textParticles advected on the surface of a fluid can exhibit fractal clustering. The local structure of a fractal set is described by its dimension , which is the exponent of a power-law relating the mass in a ball to its radius : . It is desirable to characterise the {\em shapes} of constellations of points sampling a fractal measure, as well as their masses. The simplest example is the distribution of shapes of triangles formed by triplets of points, which we investigate for fractals generated by chaotic dynamical systems. The most significant parameter describing the triangle shape is the ratio of its area to the radius of gyration squared. We show that the probability density of has a phase transition: is independent of and approximately uniform below a critical flow compressibility , which we estimate. For the distribution appears to be described by two power laws: when , and when
Exact two-dimensionalization of low-magnetic-Reynolds-number flows subject to a strong magnetic field
No full textWe investigate the behavior of flows, including turbulent flows, driven by a horizontal body-force and subject to a vertical magnetic field, with the following question in mind: for very strong applied magnetic field, is the flow mostly two-dimensional, with remaining weak three-dimensional fluctuations, or does it become exactly 2D, with no dependence along the vertical? We restrict attention to low-magnetic-Reynolds number (Rm) flow. Because liquid metals have low magnetic Prandtl number, such low- flows can have a kinetic Reynolds number as large as one million and therefore be strongly turbulent. We first focus on the quasi-static approximation, i.e. the asymptotic limit of vanishing magnetic Reynolds number Rm << 1: we prove that the flow becomes exactly 2D asymptotically in time, regardless of the initial condition and provided the interaction parameter N is larger than a threshold value. We call this property absolute two-dimensionalization: the attractor of the system is necessarily a (possibly turbulent) 2D flow. We then consider the full-magnetohydrodynamic equations and we prove that, for low enough Rm and large enough N, the flow becomes exactly two-dimensional in the long-time limit provided the initial vertically-dependent perturbations are infinitesimal. We call this phenomenon linear two-dimensionalization: the (possibly turbulent) 2D flow is an attractor of the dynamics, but it is not necessarily the only attractor of the system. Some 3D attractors may also exist and be attained for strong enough initial 3D perturbations. These results shed some light on the existence of a dissipative anomaly for magnetohydrodynamic flows subject to a strong external magnetic field
The Decay of Wall Bounded MHD Turbulence at Low RM
No full textWe have developed a new spectral method to simulate flows with very fine boundary layers present. We apply it to calculate the evolution of freely decaying MHD turbulence between isolating walls. By comparison them with results obtained in fully periodic domain we quantify the influence of the channel walls on the character of freely decaying MHD turbulence
Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6‐mercaptopurine and azathioprine.
No full textA basis of a certain module for the hyperalgebra and some applications
No full textIn the hyperalgebra of the -th Frobenius kernel of the algebraic group , we construct a basis of the
-module generated by a certain element which was given by the
author before. As its applications, we also prove some results on the
-modules and the algebra .Comment: 30 page
Borromini tuscolano
No full textLa pubblicazione propone, in versione ampliata e aggiornata, la chiave di lettura già avanzata dall’autore alcuni anni or sono in relazione all’intervento seicentesco voluto dalla famiglia Falconieri sulla più antica delle Ville Tuscolane, la Rufina, ritenendone valida la consolidata attribuzione al Borromini.
Nel volume viene data un’ampia dimostrazione dell’efficacia dell’interazione “documenti storici-rilievo architettonico”, nella ricostruzione delle fasi evolutive di una fabbrica e di come questo momento d’analisi, ove insufficientemente approfondito, possa indurre a considerazioni erronee.
Infatti, l’ipotesi diffusa in vari contributi sull’argomento riguardo alla forma dell’originario Casino della Rufina – e in particolare alla posizione della loggia verso Roma – è suffragata soltanto da incisioni d’epoca e non è mai stata scientificamente comprovata dal riscontro di un rilievo, né dal confronto attento con la pianta del nucleo originario della fabbrica conservata nelle Carte Strozzi presso l’Archivio di Stato di Firenze, ignorata o considerata – con una certa superficialità – come inattendibile.
L’ipotesi qui sostenuta valuta la “logica” dell’addizione alla Villa Rufina basandosi su considerazioni relative sia ai vari documenti iconografici sia all’attendibilità di ciascuno; il tutto è inoltre riferito al completo rilevamento dell’opera nel suo stato attuale.
Discutendo ipotesi diverse (anche attributive) emerse nel frattempo e sviluppando le considerazioni precedentemente avanzate grazie anche a un nuovo apparato iconografico che vede sfruttate le potenzialità della modellazione 3D applicate ai criteri del rilievo filologico, il lavoro tende a ribadire l’efficacia di tale metodo d’indagine, basato sul rilievo delle attuali condizioni dell’opera in associazione all’imprescindibile analisi storico-documentale.
Attraverso il medesimo impianto scientifico procedurale è inoltre sviluppata la ricostruzione filologica del fronte settentrionale, basata anche su documentazione fotografica d’epoca parzialmente inedita. Si intende così offrire un iniziale – seppur parziale – contributo alla rilettura dell’ultima fase (quella novecentesca) che ha contrassegnato la fabbrica, vedendola già alterata ai primi del XX secolo, quindi compromessa dagli eventi bellici e infine trasformata dalle operazioni di restauro/ripristino del complesso, che hanno riproposto solo parzialmente e in modo generico la precedente morfologia del manufatto.This publication proposes, in an expanded and updated version, the key that the Author had already advanced in an earlier essay which was published ten years ago, concerning the 17th century intervention on the Villa Rufina: the first one of the Ville Tuscolane (summer residences for the papal circle that rose, in the late Renaissance, on the hills at the south of Rome). The Authors assumes also to be valid the well-established attribution of this work to Francesco Borromini.
In this volume a wide demonstration is offered of the efficacy, for the aim of a reliable reconstruction of the evolutionary phases of a certain building, of the interaction between the historical documents and the architectural survey, showing also how this time of analysis can lead to incorrect or misleading considerations, when it is not carried out enough deeply.
In the second phase (the expansion of the 17th century) which characterized all the Ville Tuscolane, the Rufina, at the time owned by the Falconieri (family), was the subject of an extensive renewal. With this intervention the first bulding that had initiated the “modern rediscovery” of building activity in these places (being, in fact, the originator of the Complex) was considerably transformed with regard to its material structure, appearance and relationship with the environment. For the devising of the general plan, it is commonly ascribed to Francesco Borromini, on the basis more of archive documents than of its style.
If the decoration of the Villa has been extensively and reliably studied, the same cannot be said about the transformations that the old building underwent, especially with regard to the lost loggia towards Rome. The hypothesis that has gradually taken root, about the location of this lodge, in the various papers published on the subject, is in fact supported only by some engravings of the time (in which the Villa is depicted in a pseudo-perspectival view and only as an element amongst the many others of the Complex). It has never been scientifically proved by the check of a survey, or by a careful comparison with the plan of the original nucleus of the original factory map stored in the “Carte Strozzi” at the State Archives of Florence, that has been ignored or considered – with some superficiality – as unreliable.
The hypothesis the Author suggested since the previous essay, evaluates the “logic” of the addition Borromini made to the Villa Rufina detaching itself from these assumptions and basing itself on some specific considerations concerning the iconographic documents that have been published over the years in various contributions, evaluating the reliability of each of them. These considerations were also related to a comprehensive survey of the work in its current state, as the so far published surveys are partial or were carried out on the structure as extensively damaged by the war.
In the volume are also discussed several different hypotheses that emerged in the meantime, also on the allocation of the project, as the attribution to Borromini – which in the past had seen ups and downs, from the header of the engraving by Alessandro Specchi to the evidences provided by Paolo Portoghesi and by Angela Negro, taken from the Falconieri-Carpegna archive – has recently been the subject of a new attempt of denial.
Developing the considerations already advanced before, and using a new display of subsidiary iconography that sees the exploitation of the potential of 3d modeling when applied to the criteria of the philological surveying, this study aims at a confirmation of the effectiveness of this method of investigation, which is based on a survey of the work in its positive state in conjunction with an unavoidable historical-documentary analysis.
On the basis of this same scientific procedural system, taking as well in account many historical photographic documents, so far unpublished, is also developed a philological reconstruction of the northern front, that is proposed in the last chapter. The aim is to provide a first – although partial – contribution to the re-reading of the last phase (the 20th century), which marked the building, that had already been altered in the early years of the 20th century, then compromised by the war and finally transformed by the restoration and rehabilitation of the complex, which reconstructed the pre-existing morphology only in a partial and general way
Abstract P5-07-01: LncRNA MIR2052HG regulates ERα level and endocrine resistance through LMTK3 by recruiting early growth response protein 1
No full textAbstract
BACKGROUND: A GWAS for the MA.27 aromatase inhibitors (AIs) adjuvant trial (4,406 controls and 252 cases) identified variant (V) SNPs in a long noncoding (lnc) RNA, MIR2052HG, that were associated with longer breast cancer free interval (HR= 0.37, P= 2.15E-07). V SNPs (MAF= 0.32 to 0.42) were associated with lower MIR2052HG and ERα expression in the presence of AIs. MIR2052HG maintained ERα both by promoting AKT/FOXO3-mediated ESR1 transcription and by limiting ubiquitin-mediated ERα degradation. (Cancer Res 76:7012-23, 2016). Our goal was to further elucidate MIR2052HG's mechanism of action.
METHODS: RNA-Binding Protein Immunoprecipitation (RBPI) assays were performed to demonstrate that the transcription factor, early growth response protein 1 (EGR1), worked together with MIR2052HG to regulate lemur tyrosine kinase-3 (LMTK3) transcription in MCF7/AC1 and CAMA-1 cells. The location of EGR1 on the LMTK3 gene locus was mapped using chromatin immunoprecipitation (ChIP) assays. The co-localization of MIR2052HG RNA and the LMTK3 gene locus was determined using RNA-DNA dual fluorescent in situ hybridization (FISH). SNP effects were evaluated using a panel of human lymphoblastoid cell lines.
RESULTS: TCGA analysis revealed LMTK3 and MIR2052HG expression were highly correlated in ERα-positive breast cancer patients. We found that the MIR2052HG transcript was located in the LMTK3 gene locus by RNA-DNA FISH. Among all of the 12 potential LMTK3 transcription factors identified in the Encode database that were examined by RBPI, only EGR1 showed an interaction with MIR2052HG. CHIP assays confirmed EGR1 binding to the two putative EGR1 binding sites in LMTK3 gene.Depletion of MIR2052HG reduced the binding of EGR1 to the LMTK3 promoter and decreased LMTK3 expression, suggesting that it might function as a scaffold. Mechanistically, decreased LMTK3 levels further increased protein kinase C (PKC) activity and downstream AKT activity, leading to reduced ESR1 mRNA levels via increased pFOXO3. At the protein level, in MIR2052HG depleted cells, increased PKC activity increased the phosphorylation of MEK, ERK, and RSK1, leading to increased ERα phosphorylation at Ser167 and increased ERα degradation. Conversely, overexpression of LMTK3 in MIR2052HG depleted cells reversed these phenotypes. MIR2052HG regulated LMTK3 and ERα expression in a SNP- dependent fashion: the MIR2052HG V SNP, relative to wild-type (WT) genotype, increased LMTK3/ERα expression in response to androstenedione due to increased binding between EGR1 and the LMTK3 promoter in LCLs. However, AI treatment reduced this binding in MIR2052HG variant cells but increased binding in WT cells, resulting in decreased LMTK3/ERα in V cells and increased expression in WT cells.
CONCLUSIONS: Our findings support a model in which the protective MIR2052HG variant genotype regulates LMTK3 via MIR2052HG/EGR1, and LMTK3 regulates ERα stability via the PKC/MEK/ERK/RSK1 axis. This regulation may explain the effect of the MIR2052HG variant genotype on cell proliferation and response to AIs in MA.27. These findings provide new insight into the mechanism of action of MIR2052HG and suggest that LMTK3 may be a new therapeutic target in ERα-positive breast cancer patients treated with AIs.
Citation Format: Cairns J, Ingle JN, Shepherd LE, Kubo M, Goetz MP, Weinshilboum RM, Kalari KR, Wang L. LncRNA MIR2052HG regulates ERα level and endocrine resistance through LMTK3 by recruiting early growth response protein 1 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-07-01.</jats:p
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