Lang's Conjecture and Sharp Height Estimates for the elliptic curves y2=x3+axy^{2}=x^{3}+ax

For elliptic curves given by the equation $E_{a}: y^{2}=x^{3}+ax$, we establish the best-possible version of Lang's conjecture on the lower bound of the canonical height of non-torsion points along with best-possible upper and lower bounds for the difference between the canonical and logarithmic height.Comment: published version. Lemmas 5.1 and 6.1 now precise (with resultant refinement to Theorem 1.2). Small corrections to

Boundedness of Pseudodifferential Operators on Banach Function Spaces

We show that if the Hardy-Littlewood maximal operator is bounded on a separable Banach function space $X(\mathbb{R}^n)$ and on its associate space $X'(\mathbb{R}^n)$, then a pseudodifferential operator $\operatorname{Op}(a)$ is bounded on $X(\mathbb{R}^n)$ whenever the symbol $a$ belongs to the H\"ormander class $S_{\rho,\delta}^{n(\rho-1)}$ with $0<\rho\le 1$, $0\le\delta<1$ or to the the Miyachi class $S_{\rho,\delta}^{n(\rho-1)}(\varkappa,n)$ with $0\le\delta\le\rho\le 1$, $0\le\delta0$. This result is applied to the case of variable Lebesgue spaces $L^{p(\cdot)}(\mathbb{R}^n)$.Comment: To appear in a special volume of Operator Theory: Advances and Applications dedicated to Ant\'onio Ferreira dos Santo

Correlated analyses of D- and 15N-rich carbon grains from CR2 chondrite EET 92042

Extract from introduction: Insoluble organic matter (IOM) and matrix from primitive carbonaceous chondrites carry isotope enrichments (?D?20000', ?15N?3200�) that are comparable to those in interplanetary dust particles [1, this work]. Hence, primitive organics that formed in the protosolar cloud (PSC) – or maybe in the cold outer regions of the protoplanetary disk – survived accretion and planetary processing on the asteroids, the parent bodies of the chondrites

Correlated Microscale Isotope and Scanning Transmission X-Ray Analyses of Isotopically Anomalous Organic Matter from the CR2 Chondrite EET 92042

We discuss correlated examinations of organic matter from the CR2 chondrite EET 92042, using SIMS, STXM and other methods. We found a large, isotopically highly anomalous region of probable presolar origin that is C- and 13C-poor and 15N-rich

Secondary ion mass spectrometry and x-ray absorption near-edge structure spectroscopy of isotopically anomalous organic matter from CR1 chondrites GRO 95577

We located interstellar organics from a CR1 chondrite with NanoSIMS and analyzed FIB-extracted sections with XANES. D-rich material appears not associated with a functional group, whereas 15N-rich matter shows some affinity to nitrile functionality

Overview of the results of the organics PET Study of the cometary samples returned from comet Wild 2 by the Stardust mission

This presenation will provide an overview of the efforts and results produced by the Organics Preliminary Examination Team during their studies of the samples returned from comet Wild 2 by the Stardust spacecraft

LeukoCatch, a quick and efficient tool for the preparation of leukocyte extracts from blood

<p>Abstract</p> <p>Background</p> <p>Whole-protein extracts from peripheral blood leukocytes are ideal for basic and clinical research. However, lack of a simple preparation technique has limited the use of such extracts. The aim of this study is to develop a simple and easy system that can selectively obtain leukocyte extracts without hemoglobin.</p> <p>Methods</p> <p>A filter that captures the leukocytes but not RBCs was set at the bottom of a 10-mL medical syringe by sandwiching it between plastic stoppers. The capturing efficiency of leukocytes with this tool, called LeukoCatch, was examined using human macrophage cells (MONO-MAC-6). The abilities of LeukoCatch system to capture the leukocyte proteins and to remove the hemoglobin from RBCs were tested by western blot analysis using human blood samples.</p> <p>Results</p> <p>This study presents the development of LeukoCatch, a novel tool that allows the preparation of leukocyte extracts from blood samples within 3 min without centrifugation. Tissue-cultured human macrophage cells were tested to determine the optimal filter numbers and pass-through frequencies of LeukoCatch, which was then applied to 2-mL blood samples. Samples were passed 2~5 times through a LeukoCatch equipped with 5 filters, washed twice with phosphate-buffered saline for red cell removal, and leukocyte proteins were extracted with 0.5 mL of elution buffer. Western blot analysis of the purified extract indicated that more than 90% of hemoglobin was removed by the LeukoCatch and that the protein recovery rate of leukocytes was at least 4 times better than that of the conventional centrifugation method.</p> <p>Conclusion</p> <p>We conclude that LeukoCatch is useful not only for diagnosis at the bedside but also for basic research using blood samples or tissue culture cells.</p

The Ligand Binding Domain of GCNF Is Not Required for Repression of Pluripotency Genes in Mouse Fetal Ovarian Germ Cells

In mice, successful development and reproduction require that all cells, including germ cells, transition from a pluripotent to a differentiated state. This transition is associated with silencing of the pluripotency genes Oct4 and Nanog. Interestingly, these genes are repressed at different developmental timepoints in germ and somatic cells. Ovarian germ cells maintain their expression until about embryonic day (E) 14.5, whereas somatic cells silence them much earlier, at about E8.0. In both somatic cells and embryonic stem cells, silencing of Oct4 and Nanog requires the nuclear receptor GCNF. However, expression of the Gcnf gene has not been investigated in fetal ovarian germ cells, and whether it is required for silencing Oct4 and Nanog in that context is not known. Here we demonstrate that Gcnf is expressed in fetal ovarian germ cells, peaking at E14.5, when Oct4 and Nanog are silenced. However, conditional ablation of the ligand-binding domain of Gcnf using a ubiquitous, tamoxifen-inducible Cre indicates that Gcnf is not required for the down-regulation of pluripotency genes in fetal ovarian germ cells, nor is it required for initiation of meiosis and oogenesis. These results suggest that the silencing of Oct4 and Nanog in germ cells occurs via a different mechanism from that operating in somatic cells during gastrulation.Howard Hughes Medical InstituteNational Institutes of Health (U.S.) (2R01HG00257-20)National Human Genome Research Institute (U.S.) (2R01HG00257-20

Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

E-Cadherin Destabilization Accounts for the Pathogenicity of Missense Mutations in Hereditary Diffuse Gastric Cancer

E-cadherin is critical for the maintenance of tissue architecture due to its role in cell-cell adhesion. E-cadherin mutations are the genetic cause of Hereditary Diffuse Gastric Cancer (HDGC) and missense mutations represent a clinical burden, due to the uncertainty of their pathogenic role. In vitro and in vivo, most mutations lead to loss-of-function, although the causal factor is unknown for the majority. We hypothesized that destabilization could account for the pathogenicity of E-cadherin missense mutations in HDGC, and tested our hypothesis using in silico and in vitro tools. FoldX algorithm was used to calculate the impact of each mutation in E-cadherin native-state stability, and the analysis was complemented with evolutionary conservation, by SIFT. Interestingly, HDGC patients harbouring germline E-cadherin destabilizing mutants present a younger age at diagnosis or death, suggesting that the loss of native-state stability of E-cadherin accounts for the disease phenotype. To elucidate the biological relevance of E-cadherin destabilization in HDGC, we investigated a group of newly identified HDGC-associated mutations (E185V, S232C and L583R), of which L583R is predicted to be destabilizing. We show that this mutation is not functional in vitro, exhibits shorter half-life and is unable to mature, due to premature proteasome-dependent degradation, a phenotype reverted by stabilization with the artificial mutation L583I (structurally tolerated). Herein we report E-cadherin structural models suitable to predict the impact of the majority of cancer-associated missense mutations and we show that E-cadherin destabilization leads to loss-of-function in vitro and increased pathogenicity in vivo