TY - JOUR AB - Inclusion–exclusion is an effective method for computing the volume of a union of measurable sets. We extend it to multiple coverings, proving short inclusion–exclusion formulas for the subset of Rn covered by at least k balls in a finite set. We implement two of the formulas in dimension n=3 and report on results obtained with our software. AU - Edelsbrunner, Herbert AU - Iglesias Ham, Mabel ID - 530 JF - Computational Geometry: Theory and Applications TI - Multiple covers with balls I: Inclusion–exclusion VL - 68 ER - TY - JOUR AB - Spontaneous emission spectra of two initially excited closely spaced identical atoms are very sensitive to the strength and the direction of the applied magnetic field. We consider the relevant schemes that ensure the determination of the mutual spatial orientation of the atoms and the distance between them by entirely optical means. A corresponding theoretical description is given accounting for the dipole-dipole interaction between the two atoms in the presence of a magnetic field and for polarizations of the quantum field interacting with magnetic sublevels of the two-atom system. AU - Redchenko, Elena AU - Makarov, Alexander AU - Yudson, Vladimir ID - 307 IS - 4 JF - Physical Review A - Atomic, Molecular, and Optical Physics TI - Nanoscopy of pairs of atoms by fluorescence in a magnetic field VL - 97 ER - TY - JOUR AB - Background: Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic mutations that affect essential tumor functions or specific domains remains a controversial topic. Results: Here, we analyze 7546 individual exomes from 26 tumor types from TCGA data to explore the portion of the cancer exome under negative selection. Although we find most of the genes neutrally evolving in a pan-cancer framework, we identify essential cancer genes and immune-exposed protein regions under significant negative selection. Moreover, our simulations suggest that the amount of negative selection is underestimated. We therefore choose an empirical approach to identify genes, functions, and protein regions under negative selection. We find that expression and mutation status of negatively selected genes is indicative of patient survival. Processes that are most strongly conserved are those that play fundamental cellular roles such as protein synthesis, glucose metabolism, and molecular transport. Intriguingly, we observe strong signals of selection in the immunopeptidome and proteins controlling peptide exposition, highlighting the importance of immune surveillance evasion. Additionally, tumor type-specific immune activity correlates with the strength of negative selection on human epitopes. Conclusions: In summary, our results show that negative selection is a hallmark of cell essentiality and immune response in cancer. The functional domains identified could be exploited therapeutically, ultimately allowing for the development of novel cancer treatments. AU - Zapata, Luis AU - Pich, Oriol AU - Serrano, Luis AU - Kondrashov, Fyodor AU - Ossowski, Stephan AU - Schaefer, Martin ID - 279 JF - Genome Biology TI - Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome VL - 19 ER - TY - JOUR AB - Aged proteins can become hazardous to cellular function, by accumulating molecular damage. This implies that cells should preferentially rely on newly produced ones. We tested this hypothesis in cultured hippocampal neurons, focusing on synaptic transmission. We found that newly synthesized vesicle proteins were incorporated in the actively recycling pool of vesicles responsible for all neurotransmitter release during physiological activity. We observed this for the calcium sensor Synaptotagmin 1, for the neurotransmitter transporter VGAT, and for the fusion protein VAMP2 (Synaptobrevin 2). Metabolic labeling of proteins and visualization by secondary ion mass spectrometry enabled us to query the entire protein makeup of the actively recycling vesicles, which we found to be younger than that of non-recycling vesicles. The young vesicle proteins remained in use for up to ~ 24 h, during which they participated in recycling a few hundred times. They were afterward reluctant to release and were degraded after an additional ~ 24–48 h. We suggest that the recycling pool of synaptic vesicles relies on newly synthesized proteins, while the inactive reserve pool contains older proteins. AU - Truckenbrodt, Sven M AU - Viplav, Abhiyan AU - Jähne, Sebsatian AU - Vogts, Angela AU - Denker, Annette AU - Wildhagen, Hanna AU - Fornasiero, Eugenio AU - Rizzoli, Silvio ID - 145 IS - 15 JF - The EMBO Journal SN - 0261-4189 TI - Newly produced synaptic vesicle proteins are preferentially used in synaptic transmission VL - 37 ER - TY - JOUR AB - AtNHX5 and AtNHX6 are endosomal Na+,K+/H+ antiporters that are critical for growth and development in Arabidopsis, but the mechanism behind their action remains unknown. Here, we report that AtNHX5 and AtNHX6, functioning as H+ leak, control auxin homeostasis and auxin-mediated development. We found that nhx5 nhx6 exhibited growth variations of auxin-related defects. We further showed that nhx5 nhx6 was affected in auxin homeostasis. Genetic analysis showed that AtNHX5 and AtNHX6 were required for the function of the ER-localized auxin transporter PIN5. Although AtNHX5 and AtNHX6 were co-localized with PIN5 at ER, they did not interact directly. Instead, the conserved acidic residues in AtNHX5 and AtNHX6, which are essential for exchange activity, were required for PIN5 function. AtNHX5 and AtNHX6 regulated the pH in ER. Overall, AtNHX5 and AtNHX6 may regulate auxin transport across the ER via the pH gradient created by their transport activity. H+-leak pathway provides a fine-tuning mechanism that controls cellular auxin fluxes. AU - Fan, Ligang AU - Zhao, Lei AU - Hu, Wei AU - Li, Weina AU - Novák, Ondřej AU - Strnad, Miroslav AU - Simon, Sibu AU - Friml, Jirí AU - Shen, Jinbo AU - Jiang, Liwen AU - Qiu, Quan ID - 462 JF - Plant, Cell and Environment TI - NHX antiporters regulate the pH of endoplasmic reticulum and auxin-mediated development VL - 41 ER - TY - JOUR AB - This study treats with the influence of a symmetry-breaking transversal magnetic field on the nonlinear dynamics of ferrofluidic Taylor-Couette flow – flow confined between two concentric independently rotating cylinders. We detected alternating ‘flip’ solutions which are flow states featuring typical characteristics of slow-fast-dynamics in dynamical systems. The flip corresponds to a temporal change in the axial wavenumber and we find them to appear either as pure 2-fold axisymmetric (due to the symmetry-breaking nature of the applied transversal magnetic field) or involving non-axisymmetric, helical modes in its interim solution. The latter ones show features of typical ribbon solutions. In any case the flip solutions have a preferential first axial wavenumber which corresponds to the more stable state (slow dynamics) and second axial wavenumber, corresponding to the short appearing more unstable state (fast dynamics). However, in both cases the flip time grows exponential with increasing the magnetic field strength before the flip solutions, living on 2-tori invariant manifolds, cease to exist, with lifetime going to infinity. Further we show that ferrofluidic flow turbulence differ from the classical, ordinary (usually at high Reynolds number) turbulence. The applied magnetic field hinders the free motion of ferrofluid partials and therefore smoothen typical turbulent quantities and features so that speaking of mildly chaotic dynamics seems to be a more appropriate expression for the observed motion. AU - Altmeyer, Sebastian ID - 519 JF - Journal of Magnetism and Magnetic Materials TI - Non-linear dynamics and alternating ‘flip’ solutions in ferrofluidic Taylor-Couette flow VL - 452 ER - TY - CONF AB - We study the almost-sure termination problem for probabilistic programs. First, we show that supermartingales with lower bounds on conditional absolute difference provide a sound approach for the almost-sure termination problem. Moreover, using this approach we can obtain explicit optimal bounds on tail probabilities of non-termination within a given number of steps. Second, we present a new approach based on Central Limit Theorem for the almost-sure termination problem, and show that this approach can establish almost-sure termination of programs which none of the existing approaches can handle. Finally, we discuss algorithmic approaches for the two above methods that lead to automated analysis techniques for almost-sure termination of probabilistic programs. AU - Huang, Mingzhang AU - Fu, Hongfei AU - Chatterjee, Krishnendu ED - Ryu, Sukyoung ID - 5679 SN - 03029743 TI - New approaches for almost-sure termination of probabilistic programs VL - 11275 ER - TY - JOUR AB - The precise control of neural stem cell (NSC) proliferation and differentiation is crucial for the development and function of the human brain. Here, we review the emerging links between the alteration of embryonic and adult neurogenesis and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based modeling and the novel therapeutic targets derived from these studies. AU - Sacco, Roberto AU - Cacci, Emanuele AU - Novarino, Gaia ID - 546 IS - 2 JF - Current Opinion in Neurobiology TI - Neural stem cells in neuropsychiatric disorders VL - 48 ER - TY - GEN AB - This document contains the full list of genes with their respective significance and dN/dS values. (TXT 4499Â kb) AU - Zapata, Luis AU - Pich, Oriol AU - Serrano, Luis AU - Kondrashov, Fyodor AU - Ossowski, Stephan AU - Schaefer, Martin ID - 9812 TI - Additional file 2: Of negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome ER - TY - GEN AB - This document contains additional supporting evidence presented as supplemental tables. (XLSX 50Â kb) AU - Zapata, Luis AU - Pich, Oriol AU - Serrano, Luis AU - Kondrashov, Fyodor AU - Ossowski, Stephan AU - Schaefer, Martin ID - 9811 TI - Additional file 1: Of negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome ER -