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.     

Including the mitochondrial metabolism of <Emphasis Type="SmallCaps">l</Emphasis>-lactate in cancer metabolic reprogramming

Glucose avidity, high glycolysis and l-lactate production, regardless of oxygen availability, are the main traits of cancer metabolic reprogramming. The idea that mitochondria are dysfunctional in cancer, thus causing a glycolysis increase for ATP production and l-lactate accumulation as a dead-end product of glucose catabolism, has oriented cancer research for many years. However, it was shown that mitochondrial metabolism is essential for cancer cell proliferation and tumorigenesis and that l-lactate is a fundamental energy substrate with tumor growth-promoting and signaling capabilities. Nevertheless, the known ability of mitochondria to take up and oxidize l-lactate has remained ignored by cancer research. Beginning with a brief overview of the metabolic changes occurring in cancer, we review the present knowledge of l-lactate formation, transport, and intracellular oxidation and underline the possible role of l-lactate metabolism as energetic, signaling and anabolic support for cancer cell proliferation. These unexplored aspects of cancer biochemistry might be exploited for therapeutic benefit.     

Christian Huygens’ Lost and Forgotten Pamphlet of his Pendulum Invention

Until recently it was believed that Christian Huygens’ earliest publication of his pendulum invention was Horologium of 1658. He published the more famous general treatise, Horologium Oscillatorium, fifteen years later in 1673. Two years ago, an article1 ¹Whitestone, Sebastian, ‘The Identification and Attribution of Christiaan Huygens’ First Pendulum Clock', Antiquarian Horology, December (2008), 201–222. suggesting an unknown collaboration in developing the clock pendulum between Huygens and the Paris clockmaker Isaac Thuret, presented the evidence of Benjamin Martin, an 18th century educationalist and retailer of scientific material. Martin described a Huygens publication of 1657 and reproduced the illustration it contained. This illustration shows a different clock from the one drawn in Horologium and different also from those previously considered as Huygens’ earliest surviving examples. However, the illustration is similar to part of a plate in Horologium Oscillatorium and this similarity caused one historian to cast doubt on the existence of the 1657 publication.2 ²Plomp, R., ‘Letter', Antiquarian Horology, December (2009), 714–17. See also author's reply, ibid, 717–19. This article, with information presented for the first time, seeks to prove the existence of that work and thereby establish it in the canon of Huygens’ writings while re-examining the invention in the light that it casts.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Britton’s theory of the creation of Column $$\varPhi $$ in Babylonian System A lunar theory

The following article has two parts. The first part recounts the history of a series of discoveries by Otto Neugebauer, Bartel van der Waerden, and Asger Aaboe which step by step uncovered the meaning of Column \(\varPhi \), the mysterious leading column in Babylonian System A lunar tables. Their research revealed that Column \(\varPhi \) gives the length in days of the 223-month Saros eclipse cycle and explained the remarkable algebraic relations connecting Column \(\varPhi \) to other columns of the lunar tables describing the duration of 1, 6, or 12 synodic months. Part two presents John Britton’s theory of the genesis of Column \(\varPhi \) and the System A lunar theory starting from a fundamental equation relating the columns discovered by Asger Aaboe. This article is intended to explain and, hopefully, to clarify Britton’s original articles which many readers found difficult to follow.     

Mechanisms regulating immune surveillance of cellular stress in cancer

The purpose of this review is to explore immune-mediated mechanisms of stress surveillance in cancer, with particular emphasis on the idea that all cancers have classical hallmarks (Hanahan and Weinberg in Cell 100:57–70, 67; Cell 144:646–674, 68) that could be interrelated. We postulate that hallmarks of cancer associated with cellular stress pathways (Luo et al. in Cell 136:823–837, 101) including oxidative stress, proteotoxic stress, mitotic stress, DNA damage, and metabolic stress could define and modulate the inflammatory component of cancer. As such, the overarching goal of this review is to define the types of cellular stress that cancer cells undergo, and then to explore mechanisms by which immune cells recognize, respond to, and are affected by each stress response.     

eIF2A,an initiator tRNA carrier refractory to eIF2α kinases,functions synergistically with eIF5B

The initiator tRNA (Met-tRNA _i ^Met ) at the P site of the small ribosomal subunit plays an important role in the recognition of an mRNA start codon. In bacteria, the initiator tRNA carrier, IF2, facilitates the positioning of Met-tRNA _i ^Met on the small ribosomal subunit. Eukarya contain the Met-tRNA _i ^Met carrier, eIF2 (unrelated to IF2), whose carrier activity is inhibited under stress conditions by the phosphorylation of its α-subunit by stress-activated eIF2α kinases. The stress-resistant initiator tRNA carrier, eIF2A, was recently uncovered and shown to load Met-tRNA _i ^Met on the 40S ribosomal subunit associated with a stress-resistant mRNA under stress conditions. Here, we report that eIF2A interacts and functionally cooperates with eIF5B (a homolog of IF2), and we describe the functional domains of eIF2A that are required for its binding of Met-tRNA _i ^Met , eIF5B, and a stress-resistant mRNA. The results indicate that the eukaryotic eIF5B–eIF2A complex functionally mimics the bacterial IF2 containing ribosome-, GTP-, and initiator tRNA-binding domains in a single polypeptide.