The mammalian MAPK/ERK pathway exhibits properties of a negative feedback amplifier

Three-tiered kinase modules, such as the Raf-MEK (mitogen-activated or extracellular signal-regulated protein kinase kinase)-ERK (extracellular signal-regulated kinase) mitogen-activated protein kinase pathway, are widespread in biology, suggesting that this structure conveys evolutionarily advantageous properties. We show that the three-tiered kinase amplifier module combined with negative feedback recapitulates the design principles of a negative feedback amplifier (NFA), which is used in electronic circuits to confer robustness, output stabilization, and linearization of nonlinear signal amplification. We used mathematical modeling and experimental validation to demonstrate that the ERK pathway has properties of an NFA that (i) converts intrinsic switch-like activation kinetics into graded linear responses, (ii) conveys robustness to changes in rates of reactions within the NFA module, and (iii) stabilizes outputs in response to drug-induced perturbations of the amplifier. These properties determine biological behavior, including activation kinetics and the response to drugs.

On the Remainders Obtained in Finding the Greatest Common Divisor of Two Polynomials

In 1917 Pell (1) and Gordon used sylvester2, Sylvester’s little known and hardly ever used matrix of 1853, to compute(2) the coefficients of a Sturmian remainder — obtained in applying in Q[x], Sturm’s algorithm on two polynomials f, g ∈ Z[x] of degree n — in terms of the determinants (3) of the corresponding submatrices of sylvester2. Thus, they solved a problem that had eluded both J. J. Sylvester, in 1853, and E. B. Van Vleck, in 1900. (4) In this paper we extend the work by Pell and Gordon and show how to compute (2) the coefficients of an Euclidean remainder — obtained in finding in Q[x], the greatest common divisor of f, g ∈ Z[x] of degree n — in terms of the determinants (5) of the corresponding submatrices of sylvester1, Sylvester’s widely known and used matrix of 1840. (1) See the link http://en.wikipedia.org/wiki/Anna_Johnson_Pell_Wheeler for her biography (2) Both for complete and incomplete sequences, as defined in the sequel. (3) Also known as modified subresultants. (4) Using determinants Sylvester and Van Vleck were able to compute the coefficients of Sturmian remainders only for the case of complete sequences. (5) Also known as (proper) subresultants.

Last Interglacial synthesis of high-latitude temperature: temperature anomalies and associated errors for 4 time slices

The Last Interglacial (LIG, 129-116 thousand of years BP, ka) represents a test bed for climate model feedbacks in warmer-than-present high latitude regions. However, mainly because aligning different palaeoclimatic archives and from different parts of the world is not trivial, a spatio-temporal picture of LIG temperature changes is difficult to obtain. Here, we have selected 47 polar ice core and sub-polar marine sediment records and developed a strategy to align them onto the recent AICC2012 ice core chronology. We provide the first compilation of high-latitude temperature changes across the LIG associated with a coherent temporal framework built between ice core and marine sediment records. Our new data synthesis highlights non-synchronous maximum temperature changes between the two hemispheres with the Southern Ocean and Antarctica records showing an early warming compared to North Atlantic records. We also observe warmer than present-day conditions that occur for a longer time period in southern high latitudes than in northern high latitudes. Finally, the amplitude of temperature changes at high northern latitudes is larger compared to high southern latitude temperature changes recorded at the onset and the demise of the LIG. We have also compiled four data-based time slices with temperature anomalies (compared to present-day conditions) at 115 ka, 120 ka, 125 ka and 130 ka and quantitatively estimated temperature uncertainties that include relative dating errors. This provides an improved benchmark for performing more robust model-data comparison. The surface temperature simulated by two General Circulation Models (CCSM3 and HadCM3) for 130 ka and 125 ka is compared to the corresponding time slice data synthesis. This comparison shows that the models predict warmer than present conditions earlier than documented in the North Atlantic, while neither model is able to produce the reconstructed early Southern Ocean and Antarctic warming. Our results highlight the importance of producing a sequence of time slices rather than one single time slice averaging the LIG climate conditions.

Compilation of planktonic foraminiferal census counts from the Southern Hemisphere Oceans

We present an improved database of planktonic foraminiferal census counts from the Southern Hemisphere Oceans (SHO) from 15°S to 64°S. The SHO database combines 3 existing databases. Using this SHO database, we investigated dissolution biases that might affect faunal census counts. We suggest a depth/[DCO3]2- threshold of ~3800 m/[DCO3]2- = ~-10 to -5 µmol/kg for the Pacific and Indian Oceans, and ~4000 m/[DCO3]2- = ~0 to 10 µmol/kg for the Atlantic Ocean, under which core-top assemblages can be affected by dissolution and are less reliable for paleo-sea surface temperature (SST) reconstructions. We removed all core-tops beyond these thresholds from the SHO database. This database has 598 core-tops and is able to reconstruct past SST variations from 2° to 25.5°C, with a root mean square error of 1.00°C, for annual temperatures. To inspect dissolution affects SST reconstruction quality, we tested the data base with two "leave-one-out" tests, with and without the deep core-tops. We used this database to reconstruct Summer SST (SSST) over the last 20 ka, using the Modern Analog Technique method, on the Southeast Pacific core MD07-3100. This was compared to the SSST reconstructed using the 3 databases used to compile the SHO database. Thus showing that the reconstruction using the SHO database is more reliable, as its dissimilarity values are the lowest. The most important aspect here is the importance of a bias-free, geographic-rich, database. We leave this dataset open-ended to future additions; the new core-tops must be carefully selected, with their chronological frameworks, and evidence of dissolution assessed.

Desenvolvimento de bionanocompósitos: nano e microcristais de celulose com poli (álcool vinílico) e poli (ácido lático)

This work has the main objective to obtain nano and microcrystals of cellulose, extracted from the pineapple leaf fibres (PALF), as reinforcement for the manufacture of biocomposite films with polymeric matrices of Poly(vinyl alcohol) (PVA) and Poly(lactic acid) (PLA). The polymer matrices and the nano and microcrystals of cellulose were characterised by means of TGA, FTIR and DSC. The analysis was performed on the pineapple leaves to identify the macro and micronutrients. The fibers of the leaves of the pineapple were extracted in a desfibradeira mechanical. The PALF extracted were washed to remove washable impurities and subsequently treated with sodium hydroxide (NaOH) and sodium hypochlorite (NaClO) in the removal of impurities, such as fat, grease, pectates, pectin and lignin. The processed PALF fibers were hydrolysed in sulfuric acid (H2SO4) at a concentration of 13.5 %, to obtain nano and microcrystals of cellulose. In the manufacture of biocomposite films, concentrations of cellulose, 0 %, 1 %, 3 %, 6 %, 9% and 12% were used as reinforcement to the matrices of PVA and PLA. The PVA was dissolved in distilled water at 80 ± 5 oC and the PLA was dissolved in dichloromethane at room temperature. The manufacture of biocompósitos in the form of films was carried out by "casting". Tests were carried out to study the water absorption by the films and mechanical test of resistance to traction according to ASTM D638-10 with a velocity of 50 mm/min.. Chi-square statistical test was used to check for the existence of significant differences in the level of 0.05: the lengths of the PALF, lengths of the nano and microcrystals of cellulose and the procedures used for the filtration using filter syringe of 0.2 μm or filtration and centrifugation. The hydrophilicity of biocompósitos was analysed by measuring the contact angle and the thickness of biocompósitos were compared as well as the results of tests of traction. Statistical T test - Student was also applied with the significance level (0.05). In biodegradation, Sturm test of standard D5209 was used. Nano and microcrystals of cellulose with lengths ranging from 7.33 nm to 186.17 nm were found. The PVA films showed average thicknesses of 0.153 μm and PLA 0.210 μm. There is a strong linear correlation directly proportional between the traction of the films of PVA and the concentration of cellulose in the films (composite) (0,7336), while the thickness of the film was correlated in 0.1404. Nano and microcrystals of cellulose and thickness together, correlated to 0.8740. While the correlation between the cellulose content and tensile strength was weak and inversely proportional (- 0,0057) and thickness in -0.2602, totaling -0,2659 in PLA films. This can be attributed to the nano and microcrystals of cellulose not fully adsorbed to the PLA matrix. In the comparison of the results of the traction of the two polymer matrices, the nano and microcrystals have helped in reducing the traction of the films (composite) of PLA. There was still the degradation of the film of PVA, within a period of 20 days, which was not seen in the PLA film, on the other hand, the observations made in the literature, the average time to start the degradation is above 60 days. What can be said that the films are biodegradable composites, with hydrophilicity and the nano and microcrystals of cellulose, contribute positively in the improvement of the results of polymer matrices used.

O paradoxo da superdifusão de uma caminhada aleatória com memória exponencial

The random walk models with temporal correlation (i.e. memory) are of interest in the study of anomalous diffusion phenomena. The random walk and its generalizations are of prominent place in the characterization of various physical, chemical and biological phenomena. The temporal correlation is an essential feature in anomalous diffusion models. These temporal long-range correlation models can be called non-Markovian models, otherwise, the short-range time correlation counterparts are Markovian ones. Within this context, we reviewed the existing models with temporal correlation, i.e. entire memory, the elephant walk model, or partial memory, alzheimer walk model and walk model with a gaussian memory with profile. It is noticed that these models shows superdiffusion with a Hurst exponent H > 1/2. We study in this work a superdiffusive random walk model with exponentially decaying memory. This seems to be a self-contradictory statement, since it is well known that random walks with exponentially decaying temporal correlations can be approximated arbitrarily well by Markov processes and that central limit theorems prohibit superdiffusion for Markovian walks with finite variance of step sizes. The solution to the apparent paradox is that the model is genuinely non-Markovian, due to a time-dependent decay constant associated with the exponential behavior. In the end, we discuss ideas for future investigations.

Strong primeness in fuzzy environment

The main aim of this investigation is to propose the notion of uniform and strong primeness in fuzzy environment. First, it is proposed and investigated the concept of fuzzy strongly prime and fuzzy uniformly strongly prime ideal. As an additional tool, the concept of t/m systems for fuzzy environment gives an alternative way to deal with primeness in fuzzy. Second, a fuzzy version of correspondence theorem and the radical of a fuzzy ideal are proposed. Finally, it is proposed a new concept of prime ideal for Quantales which enable us to deal with primeness in a noncommutative setting.

Strong primeness in fuzzy environment

The main aim of this investigation is to propose the notion of uniform and strong primeness in fuzzy environment. First, it is proposed and investigated the concept of fuzzy strongly prime and fuzzy uniformly strongly prime ideal. As an additional tool, the concept of t/m systems for fuzzy environment gives an alternative way to deal with primeness in fuzzy. Second, a fuzzy version of correspondence theorem and the radical of a fuzzy ideal are proposed. Finally, it is proposed a new concept of prime ideal for Quantales which enable us to deal with primeness in a noncommutative setting.

Of madness and many-valuedness: an investigation into Suszko's Thesis

Suszko’s Thesis is a philosophical claim regarding the nature of many-valuedness. It was formulated by the Polish logician Roman Suszko during the middle 70s and states the existence of “only but two truth values”. The thesis is a reaction against the notion of many-valuedness conceived by Jan Łukasiewicz. Reputed as one of the modern founders of many-valued logics, Łukasiewicz considered a third undetermined value in addition to the traditional Fregean values of Truth and Falsehood. For Łukasiewicz, his third value could be seen as a step beyond the Aristotelian dichotomy of Being and non-Being. According to Suszko, Łukasiewicz’s ideas rested on a confusion between algebraic values (what sentences describe/denote) and logical values (truth and falsity). Thus, Łukasiewicz’s third undetermined value is no more than an algebraic value, a possible denotation for a sentence, but not a genuine logical value. Suszko’s Thesis is endorsed by a formal result baptized as Suszko’s Reduction, a theorem that states every Tarskian logic may be characterized by a two-valued semantics. The present study is intended as a thorough investigation of Suszko’s thesis and its implications. The first part is devoted to the historical roots of many-valuedness and introduce Suszko’s main motivations in formulating the double character of truth-values by drawing the distinction in between algebraic and logical values. The second part explores Suszko’s Reduction and presents the developments achieved from it; the properties of two-valued semantics in comparison to many-valued semantics are also explored and discussed. Last but not least, the third part investigates the notion of logical values in the context of non-Tarskian notions of entailment; the meaning of Suszko’s thesis within such frameworks is also discussed. Moreover, the philosophical foundations for non-Tarskian notions of entailment are explored in the light of recent debates concerning logical pluralism.

Contribuição ao estudo de treliças não lineares considerando efeitos térmicos

This work presents the numerical analysis of nonlinear trusses summited to thermomechanical actions with Finite Element Method (FEM). The proposed formulation is so-called positional FEM and it is based on the minimum potential energy theorem written according to nodal positions, instead of displacements. The study herein presented considers the effects of geometric and material nonlinearities. Related to dynamic problems, a comparison between different time integration algorithms is performed. The formulation is extended to impact problems between trusses and rigid wall, where the nodal positions are constrained considering nullpenetration condition. In addition, it is presented a thermodynamically consistent formulation, based on the first and second law of thermodynamics and the Helmholtz free-energy for analyzing dynamic problems of truss structures with thermoelastic and thermoplastic behavior. The numerical results of the proposed formulation are compared with examples found in the literature.

Transiente superdifusivo em caminhadas aleatórias com perfil de memória q-exponencial

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Alcuni applicazioni dell'azione di un gruppo su un insieme

la tesi tratta alcuni risultati e applicazioni relative alla teoria delle azioni di gruppi su insiemi finiti, come l'equazione delle classi e il teorema di Cauchy. Infine illustra l'uso di tali risultati nella rappresentazione tramite permutazioni.

Luoghi geometrici e curve celebri

Scopo di questo elaborato è affrontare lo studio di luoghi geometrici piani partendo dagli esempi più semplici che gli studenti incontrano nel loro percorso scolastico, per poi passare a studiare alcune curve celebri che sono definite come luoghi geometrici. Le curve nell'elaborato vengono disegnate con l'ausilio di Geogebra, con il quale sono state preparate delle animazioni da mostrare agli studenti. Di alcuni luoghi si forniscono dapprima le equazioni parametriche e successivamente, attraverso il teorema di eliminazione e il software Singular, viene ricavata l'equazione cartesiana.

Tabelle di Young e statistiche sulle permutazioni

La presente tesi è suddivisa in due parti: nella prima parte illustriamo le definizioni e i relativi risultati della teoria delle tabelle di Young, introdotte per la prima volta nel 1900 da Alfred Young; mentre, nella seconda parte, diamo la nozione di numeri Euleriani e di Polinomi Euleriani. Nel primo capitolo abbiamo introdotto i concetti di diagramma di Young e di tabelle di Young standard. Inoltre, abbiamo fornito la formula degli uncini per contare le tabelle di Young della stessa forma. Il primo capitolo è focalizzato sul teorema di Robinson-Schensted, che stabilisce una corrispondenza biunivoca tra le permutazioni di Sn e le coppie di tabelle di Young standard della stessa forma. Ne deriva un'importante conseguenza che consiste nel poter trovare in modo efficiente la massima sottosequenza crescente di una permutazione. Una volta definite le operazioni di evacuazione e "le jeu de taquin" relative alle tabelle di Young, illustriamo una serie di risultati riferibili alla corrispondenza biunivoca R-S che variano in base alla permutazione che prendiamo in considerazione. In particolare, enunciamo il teorema di simmetria di M.P.Schüztenberger, che dimostriamo attraverso la costruzione geometrica di Viennot. Nel secondo capitolo, dopo aver dato la definizione di discesa di una permutazione, descriviamo altre conseguenze della corrispondenza biunivoca R-S: vediamo così che esiste una relazione tra le discese di una permutazione e la coppia di tabelle di Young associata. Abbiamo trattato approfonditamente i numeri Euleriani, indicati con A(n,k) = ]{σ ∈ Sn;d(σ) = k}, dove d(σ) indica il numero di discese di una permutazione. Descriviamo le loro proprietà e simmetrie e vediamo che sono i coefficienti di particolari polinomi, detti Polinomi Euleriani. Infine, attraverso la nozione di eccedenza di una permutazione e la descrizione della mappa di Foata arriviamo a dimostrare un importante risultato: A(n,k) conta anche il numero di permutazioni di Sn con k eccedenze.