Coincidence and reproducibility in the EHT black hole experiment

This paper discusses some philosophical aspects related to the recent publication of the experimental results of the 2017 black hole experiment, namely the first image of the supermassive black hole at the center of galaxy M87. In this paper I present a philosophical analysis of the 2017 Event Horizon Telescope (EHT) black hole experiment. I first present Hacking's philosophy of experimentation. Hacking gives his taxonomy of elements of laboratory science and distinguishes a list of elements. I show that the EHT experiment conforms to major elements from Hacking's list. I then describe with the help of Galison's Philosophy of the Shadow how the EHT Collaboration created the famous black hole image. Galison outlines three stages for the reconstruction of the black hole image: Socio-Epistemology, Mechanical Objectivity, after which there is an additional Socio-Epistemology stage. I subsequently present my own interpretation of the reconstruction of the black hole image and I discuss model fitting to data. I suggest that the main method used by the EHT Collaboration to assure trust in the results of the EHT experiment is what philosophers call the Argument from Coincidence. I show that using this method for the above purpose is problematic. I present two versions of the Argument from Coincidence: Hacking's Coincidence and Cartwright's Reproducibility by which I analyse the EHT experiment. The same estimation of the mass of the black hole is reproduced in four different procedures. The EHT Collaboration concludes: the value we have converged upon is robust. I analyse the mass measurements of the black hole with the help of Cartwright's notion of robustness. I show that the EHT Collaboration construe Coincidence/Reproducibility as Technological Agnosticism and I contrast this interpretation with van Fraassen's scientific agnosticism.     

Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1

Genomic imprinting is an epigenetic modification that results in expression from only one of the two parental copies of a gene. Differences in methylation between the two parental chromosomes are often observed at or near imprinted genes. Beckwith-Wiedemann syndrome (BWS), which predisposes to cancer and excessive growth, results from a disruption of imprinted gene expression in chromosome band 11p15.5. One third of individuals with BWS lose maternal-specific methylation at KvDMR1, a putative imprinting control region within intron 10 of the KCNQ1 gene, and it has been proposed that this epimutation results in aberrant imprinting and, consequently, BWS1, 2. Here we show that paternal inheritance of a deletion of KvDMR1 results in the de-repression in cis of six genes, including Cdkn1c, which encodes cyclin-dependent kinase inhibitor 1C. Furthermore, fetuses and adult mice that inherited the deletion from their fathers were 20-25% smaller than their wildtype littermates. By contrast, maternal inheritance of this deletion had no effect on imprinted gene expression or growth. Thus, the unmethylated paternal KvDMR1 allele regulates imprinted expression by silencing genes on the paternal chromosome. These findings support the hypothesis that loss of methylation in BWS patients activates the repressive function of KvDMR1 on the maternal chromosome, resulting in abnormal silencing of CDKN1C and the development of BWS.     

Genetic recombination is directed away from functional genomic elements in mice

Genetic recombination occurs during meiosis, the key developmental programme of gametogenesis. Recombination in mammals has been recently linked to the activity of a histone H3 methyltransferase, PR domain containing 9 (PRDM9), the product of the only known speciation-associated gene in mammals. PRDM9 is thought to determine the preferred recombination sites--recombination hotspots--through sequence-specific binding of its highly polymorphic multi-Zn-finger domain. Nevertheless, Prdm9 knockout mice are proficient at initiating recombination. Here we map and analyse the genome-wide distribution of recombination initiation sites in Prdm9 knockout mice and in two mouse strains with different Prdm9 alleles and their F(1) hybrid. We show that PRDM9 determines the positions of practically all hotspots in the mouse genome, with the exception of the pseudo-autosomal region (PAR)--the only area of the genome that undergoes recombination in 100% of cells. Surprisingly, hotspots are still observed in Prdm9 knockout mice, and as in wild type, these hotspots are found at H3 lysine 4 (H3K4) trimethylation marks. However, in the absence of PRDM9, most recombination is initiated at promoters and at other sites of PRDM9-independent H3K4 trimethylation. Such sites are rarely targeted in wild-type mice, indicating an unexpected role of the PRDM9 protein in sequestering the recombination machinery away from gene-promoter regions and other functional genomic elements.     

Specific structural features of LnZrOx (Ln: La, Sm) mixed oxides prepared by different methods

LnZrOx(Ln: La, Sm) mixed oxides of Ln: Zr = 1 were prepared by different methods(complex polymerized method, sorption of cations on starch from aqueous salt solution and conventional co-precipitation with additional redispersion of precipitate by ultra sound) and calcined at 700–1300 °C. Their specific structural features and changes were studied and discussed. Various characterization methods were used such as X-ray diffraction,Electron microscopy, Fourier-transform infrared and Raman spectroscopy, UV–Vis spectroscopy, X-Ray absorption fine structure and X-ray photoelectron spectroscopy.The formation of pyrochlore structure occurred at 1100–1300 °C from fluorite-like pseudocubic phase ZrO_2 regardless the method of preparation. This phase had a block-like structure consisting of ZrO_2 nanocrystals stabilized by Ln cations and residual anions such as hydroxyls and carbonates. The desorption of such anions with heating already started at 900 °C and lead to local changes of Zr cations coordination to octahedral and to the formation of pyrochlore nanodomains inclusions within fluorite-like phase. The increased cation mobility and further elimination of anions caused by further heating was accompanied by the formation of bulk pyrochlore phase at 1100–1300 °C. Even after calcination at 1300 °C the local microheterogeneity as well as defects were identified at domains boundaries or sintered microstructure. These specific features of the formed pyrochlores depend on the method of preparation.     

Rock-magnetic investigation of Siberia loess and its implication

Multiple-rock magnetic investigations conducted on the loess-paleosol sequences at Kurtak in Southwestern Siberia reveal that the mass-normalized low-field magnetic susceptibility profiles reflect changes in lithology between relatively unweathered primary loess of glacial periods and the interglacial paleosols. Maxima in susceptibility values correspond with the least-weathered loess horizons, and minima with the humic horizons of soils. Frequency-dependent susceptibility of the loess-paleosol sequences at Kurtak is very low and practically uniform, indicating the dominance of non-SP ferrimagnetic minerals and negligible pedogenesis. The history of temperature-dependence of susceptibility (TDS) and stepwise acquisition of the isothermal remanent magnetization (SIRM) have confirmed that magnetite is predominant magnetic mineral, and only few maghemite and probably hematite are present within the studied section. Anisotropy of the magnetic susceptibility (AMS) can be used to monitor tilt and disturbance of the sedimentary layers, and also to provide information about the paleo-transport direction for Siberia loess.     

Geometrical constructions equivalent to non-linear algebraic transformations of the plane in Newton's early papers

Summary The theory of constructive formation of plane algebraic curves in Newton's writings is discussed in § 1: the apparatus by which Newton forms the curves, Newton's theorems on forming unicursal curves, his theory of conics, and his theory of (m, n) correspondence. Special Cremona plane and space transformations obtained by Newton's organic method are dealt with in § 2. The article ends with § 3, which shows two different directions in the theory of the constructive formation of plane algebraic curves in the XVIII-XIXth centuries. A synopsis is appended.Abbreviations MPN The Mathematical Papers of Isaac Newton, edited by D. T. Whiteside, Vols. 1–3, Cambridge, 1967–1969 - Hudson H. Hudson, Cremona Transformations in Plane and Space, Cambridge, 1927 - PT (abridged) Philosophical Transactions of the Royal Society 1665–1800 (abridged), London, 1809 - Andreev ₁ K. A. Andreev, On geometrical correspondences ... (in Russian), Moscow, 1879 - Andreev ₂ K. A. Andreev, On the Geometrical Formation of Plane Curves (in Russian), Kharkov, 1875     

SbsB structure and lattice reconstruction unveil Ca2+ triggered S-layer assembly

S-layers are regular two-dimensional semipermeable protein layers that constitute a major cell-wall component in archaea and many bacteria. The nanoscale repeat structure of the S-layer lattices and their self-assembly from S-layer proteins (SLPs) have sparked interest in their use as patterning and display scaffolds for a range of nano-biotechnological applications. Despite their biological abundance and the technological interest in them, structural information about SLPs is limited to truncated and assembly-negative proteins. Here we report the X-ray structure of the SbsB SLP of Geobacillus stearothermophilus PV72/p2 by the use of nanobody-aided crystallization. SbsB consists of a seven-domain protein, formed by an amino-terminal cell-wall attachment domain and six consecutive immunoglobulin-like domains, that organize into a φ-shaped disk-like monomeric crystallization unit stabilized by interdomain Ca(2+) ion coordination. A Ca(2+)-dependent switch to the condensed SbsB quaternary structure pre-positions intermolecular contact zones and renders the protein competent for S-layer assembly. On the basis of crystal packing, chemical crosslinking data and cryo-electron microscopy projections, we present a model for the molecular organization of this SLP into a porous protein sheet inside the S-layer. The SbsB lattice represents a previously undescribed structural model for protein assemblies and may advance our understanding of SLP physiology and self-assembly, as well as the rational design of engineered higher-order structures for biotechnology.     

Crystal structure of the CorA Mg2+ transporter

The magnesium ion, Mg2+, is essential for myriad biochemical processes and remains the only major biological ion whose transport mechanisms remain unknown. The CorA family of magnesium transporters is the primary Mg2+ uptake system of most prokaryotes and a functional homologue of the eukaryotic mitochondrial magnesium transporter. Here we determine crystal structures of the full-length Thermotoga maritima CorA in an apparent closed state and its isolated cytoplasmic domain at 3.9 A and 1.85 A resolution, respectively. The transporter is a funnel-shaped homopentamer with two transmembrane helices per monomer. The channel is formed by an inner group of five helices and putatively gated by bulky hydrophobic residues. The large cytoplasmic domain forms a funnel whose wide mouth points into the cell and whose walls are formed by five long helices that are extensions of the transmembrane helices. The cytoplasmic neck of the pore is surrounded, on the outside of the funnel, by a ring of highly conserved positively charged residues. Two negatively charged helices in the cytoplasmic domain extend back towards the membrane on the outside of the funnel and abut the ring of positive charge. An apparent Mg2+ ion was bound between monomers at a conserved site in the cytoplasmic domain, suggesting a mechanism to link gating of the pore to the intracellular concentration of Mg2+.