Wnt–Notch signalling crosstalk in development and disease

The Notch and Wnt pathways are two of only a handful of highly conserved signalling pathways that control cell-fate decisions during animal development (Pires-daSilva and Sommer in Nat Rev Genet 4: 39–49, 2003). These two pathways are required together to regulate many aspects of metazoan development, ranging from germ layer patterning in sea urchins (Peter and Davidson in Nature 474: 635–639, 2011) to the formation and patterning of the fly wing (Axelrod et al in Science 271:1826–1832, 1996; Micchelli et al in Development 124:1485–1495, 1997; Rulifson et al in Nature 384:72–74, 1996), the spacing of the ciliated cells in the epidermis of frog embryos (Collu et al in Development 139:4405–4415, 2012) and the maintenance and turnover of the skin, gut lining and mammary gland in mammals (Clayton et al in Nature 446:185–189, 2007; Clevers in Cell 154:274–284, 2013; Doupe et al in Dev Cell 18:317–323, 2010; Lim et al in Science 342:1226–1230, 2013; Lowell et al in Curr Biol 10:491–500, 2000; van et al in Nature 435:959–963, 2005; Yin et al in Nat Methods 11:106–112, 2013). In addition, many diseases, including several cancers, are caused by aberrant signalling through the two pathways (Bolós et al in Endocr Rev 28: 339–363, 2007; Clevers in Cell 127: 469–480, 2006). In this review, we will outline the two signalling pathways, describe the different points of interaction between them, and cover how these interactions influence development and disease.     

Emergence of classical trajectories in quantum systems: the cloud chamber problem in the analysis of Mott (1929)

We analyze the paper “The wave mechanics of $\alpha $ -ray tracks” Mott (Proc R Soc Lond A 126:79–84, 1929), published in 1929 by N. F. Mott. In particular, we discuss the theoretical context in which the paper appeared and give a detailed account of the approach used by the author and the main result attained. Moreover, we comment on the relevance of the work not only as far as foundations of Quantum Mechanics are concerned but also as the earliest pioneering contribution in decoherence theory.     

Geometric division problems, quadratic equations, and recursive geometric algorithms in Mesopotamian mathematics

Most of what is told in this paper has been told before by the same author, in a number of publications of various kinds, but this is the first time that all this material has been brought together and treated in a uniform way. Smaller errors in the earlier publications are corrected here without comment. It has been known since the 1920s that quadratic equations played a prominent role in Babylonian mathematics. See, most recently, Høyrup (Hist Sci 34:1–32, 1996, and Lengths, widths, surfaces: a portrait of old Babylonian algebra and its kin. Springer, New York, 2002). What has not been known, however, is how quadratic equations came to play that role, since it is difficult to think of any practical use for quadratic equations in the life and work of a Babylonian scribe. One goal of the present paper is to show how the need to find solutions to quadratic equations actually arose in Mesopotamia not later than in the second half of the third millennium BC, and probably before that in connection with certain geometric division of property problems. This issue was brought up for the first time in Friberg (Cuneiform Digit Lib J 2009:3, 2009). In this connection, it is argued that the tool used for the first exact solution of a quadratic equation was either a clever use of the “conjugate rule” or a “completion of the square,” but that both methods ultimately depend on a certain division of a square, the same in both cases. Another, closely related goal of the paper is to discuss briefly certain of the most impressive achievements of anonymous Babylonian mathematicians in the first half of the second millennium BC, namely recursive geometric algorithms for the solution of various problems related to division of figures, more specifically trapezoidal fields. For an earlier, comprehensive (but less accessible) treatment of these issues, see Friberg (Amazing traces of a Babylonian origin in Greek mathematics. WorldScientific, Singapore 2007b, Ch. 11 and App. 1).     

The development of the Laplace transform, 1737–1937

This paper, the first of two, follows the development of theLaplace Transform from its earliest beginnings withEuler, usually dated at 1737, to the year 1880, whenSpitzer was its major, if himself relatively minor, protagonist. The coverage aims at completeness, and shows the state which the technique reached in the hands of its greatest exponent to that time,Petzval. A sequel will trace the development of the modern theory from its beginnings withPoincaré to its present form, due toDoetsch.     

Heterogeneous responses of canine basilar and middle cerebral arteries to serotonin at normal and high CO2 tension

The responses of basilar arteries (BAs) to serotonin were attenuated by high \(P_{CO_2 } \) (86±1 mm Hg) and the pH matched acidotic solution ( \(P_{CO_2 } \) 37±1 mm Hg), whereas the responses of middle cerebral arteries (MCAs) were not. High \(P_{CO_2 } \) decreased the basal tone of both arteries, and the changes in basal tone due to high \(P_{CO_2 } \) were not influenced by 3×10^?7 M imipramine, 10^?5 M pargyline or 10^?4 M aspirin. The responses of BAs to serotonin were attenuated by high \(P_{CO_2 } \) in the presence of imipramine, pargyline and aspirin. The responses of MCAs to serotonin were not influenced by high \(P_{CO_2 } \) in the presence of pargyline and aspirin, but attenuated by high \(P_{CO_2 } \) in the presence of imipramine.     

Generating new neurons to circumvent your fears: the role of IGF signaling

Extinction of fear memory is a particular form of cognitive function that is of special interest because of its involvement in the treatment of anxiety and mood disorders. Based on recent literature and our previous findings (EMBO J 30(19):4071–4083, 2011), we propose a new hypothesis that implies a tight relationship among IGF signaling, adult hippocampal neurogenesis and fear extinction. Our proposed model suggests that fear extinction-induced IGF2/IGFBP7 signaling promotes the survival of neurons at 2–4 weeks old that would participate in the discrimination between the original fear memory trace and the new safety memory generated during fear extinction. This is also called “pattern separation”, or the ability to distinguish similar but different cues (e.g., context). To understand the molecular mechanisms underlying fear extinction is therefore of great clinical importance.     

Two problems in Aristarchus’s treatise on the sizes and distances of the sun and moon

The book of Aristarchus of Samos, On the distances and sizes of the sun and moon, is one of the few pre-Ptolemaic astronomical works that have come down to us in complete or nearly complete form. The simplicity and cleverness of the basic ideas behind the calculations are often obscured in the reading of the treatise by the complexity of the calculations and reasoning. Part of the complexity could be explained by the lack of trigonometry and part by the fact that Aristarchus appears unwilling to make some simplifications that could be simply taken for granted. But an important part of the complexities is due to some unnecessary inconsistencies, as recently discovered by Berggren and Sidoli (Arch Hist Exact Sci 61:213–254, 2007). In the first part of this paper, I will try to show that some of these inconsistencies are just apparent. But the complexity of the calculations and reasoning is not the only reason that could disturb a reader of the treatise. The great inaccuracy—even for the measurement methods and instruments available at those times—of one of the three input values of the treatise is really astonishing. In the sixth and last hypothesis, Aristarchus states that the moon’s apparent size is equal to 2 $^{\circ }$ , while the correct value is one-fourth of that. Some attempts have been made in order to explain such a big value, but all of them have problems. In the second part of this paper, I will propose a new speculative but plausible explanation of the origin of this value.     

Cyclotomie et formes quadratiques dans l’œuvre arithmétique d’Augustin-Louis Cauchy (1829–1840)

Augustin-Louis Cauchy publie une majorité de ses recherches arithmétiques entre 1829 et 1840. Celles-ci ne sont pourtant qu’évoquées dans certaines histoires de la théorie des nombres centrées sur les lois de réciprocité ou sur la théorie des nombres algébriques. Elles y sont décrites comme contenant quelques résultats similaires à ceux de Gauss, Jacobi ou Dirichlet mais de manière incomplète et désordonnée. L’objectif de cet article est de présenter une analyse des textes arithmétiques de Cauchy publiés entre 1829 et 1840 pour montrer qu’ils contiennent au contraire un ensemble cohérent de résultats en lien avec les formes quadratiques $4p^{\mu }=x^2+ny^2$ , où $p$ est un nombre premier et $n$ un diviseur de $p-1$ . Nous discuterons également la forme particulière de ce corpus et la stratégie utilisée pour retrouver les lignes directrices du travail de Cauchy. Augustin-Louis Cauchy published most of his arithmetical research between 1829 and 1840. These are however only mentioned in some number theory history centered on reciprocity laws or on theory of algebraic numbers. They are described as containing some results similar to those of Gauss, Jacobi and Dirichlet but in a incomplete and disorganized way. The objective of this paper is to present an analysis of Cauchy’s arithmetical texts published between 1829 and 1840 to show that they contain a rather consistent set of results related to quadratic forms $4p^{\mu } = x ^2 + ny ^2 $ , where $p$ is a prime and $n$ a divisor of $ p-1 $ . We will also discuss the particular form of this body of texts and the strategy we used to find the guidelines of the work of Cauchy.     

Leibniz’s syncategorematic infinitesimals

In contrast with some recent theories of infinitesimals as non-Archimedean entities, Leibniz’s mature interpretation was fully in accord with the Archimedean Axiom: infinitesimals are fictions, whose treatment as entities incomparably smaller than finite quantities is justifiable wholly in terms of variable finite quantities that can be taken as small as desired, i.e. syncategorematically. In this paper I explain this syncategorematic interpretation, and how Leibniz used it to justify the calculus. I then compare it with the approach of Smooth Infinitesimal Analysis, as propounded by John Bell. I find some salient differences, especially with regard to higher-order infinitesimals. I illustrate these differences by a consideration of how each approach might be applied to propositions of Newton’s Principia concerning the derivation of force laws for bodies orbiting in a circle and an ellipse. “If the Leibnizian calculus needs a rehabilitation because of too severe treatment by historians in the past half century, as Robinson suggests (1966, 250), I feel that the legitimate grounds for such a rehabilitation are to be found in the Leibnizian theory itself.”—(Bos 1974–1975, 82–83).      

Investigations of the coordinates in Ptolemy’s Geographike Hyphegesis Book 8

In Book 8 of his Geographike Hyphegesis Ptolemy gives coordinates for ca. 360 so-called noteworthy cities. These coordinates are the time difference to Alexandria, the length of the longest day, and partly the ecliptic distance from the summer solstice. The supposable original conversions between the coordinates in Book 8 and the geographical coordinates in the location catalogue of Books 2–7 including the underlying parameters and tabulations are here reconstructed. The results document the differences between the ${\Omega}$ - and ${\Xi}$ -recension. The known difference in the longitude of Alexandria underlying the conversion of the longitudes is examined more closely. For the ecliptic distances from the summer solstice of the ${\Omega}$ -recension, it is revealed that they were originally computed by means of a so far undiscovered approximate, linear conversion. Further it is shown that the lengths of the longest day could be based on a linear interpolation of the data in the Mathematike Syntaxis 2.6.     

Isaac Newton’s ‘Of Quadrature by Ordinates’

In Of Quadrature by Ordinates (1695), Isaac Newton tried two methods for obtaining the Newton–Cotes formulae. The first method is extrapolation and the second one is the method of undetermined coefficients using the quadrature of monomials. The first method provides $n$ -ordinate Newton–Cotes formulae only for cases in which $n=3,4$ and 5. However this method provides another important formulae if the ratios of errors are corrected. It is proved that the second method is correct and provides the Newton–Cotes formulae. Present significance of each of the methods is given.     

Evolution and biology of supernumerary B chromosomes

B chromosomes (Bs) are dispensable components of the genome exhibiting non-Mendelian inheritance and have been widely reported on over several thousand eukaryotes, but still remain an evolutionary mystery ever since their first discovery over a century ago [1]. Recent advances in genome analysis have significantly improved our knowledge on the origin and composition of Bs in the last few years. In contrast to the prevalent view that Bs do not harbor genes, recent analysis revealed that Bs of sequenced species are rich in gene-derived sequences. We summarize the latest findings on supernumerary chromosomes with a special focus on the origin, DNA composition, and the non-Mendelian accumulation mechanism of Bs.     

Pre-Euclidean geometry and Aeginetan coin design: some further remarks

Some ancient Greek coins from the island state of Aegina depict peculiar geometric designs. Hitherto they have been interpreted as anticipations of some Euclidean propositions. But this paper proposes geometrical constructions which establish connections to pre-Euclidean treatments of incommensurability. The earlier Aeginetan coin design from about 500 bc onwards appears as an attempt not only to deal with incommensurability but also to conceal it. It might be related to Plato’s dialogue Timaeus. The newer design from 404 bc onwards reveals incommensurability, namely in the context of ‘doubling the square’. It thereby covers the same topic but a different geometry as passages in Plato’s dialogue Meno (385 bc). This coin design incorporates important elements of ancient Greek geometrical analysis of the fifth century bc like the gnomon, Hippocrates’ squaring of the lunule (ca. 430 bc), and a geometrical version of monetary equivalence. Through this venue, the design’s conceptual lineage might be traced as far back as Heraclitus’ cosmology of about 500 bc.