@article{3308, abstract = {We study multivariate normal models that are described by linear constraints on the inverse of the covariance matrix. Maximum likelihood estimation for such models leads to the problem of maximizing the determinant function over a spectrahedron, and to the problem of characterizing the image of the positive definite cone under an arbitrary linear projection. These problems at the interface of statistics and optimization are here examined from the perspective of convex algebraic geometry.}, author = {Sturmfels, Bernd and Caroline Uhler}, journal = {Annals of the Institute of Statistical Mathematics}, number = {4}, pages = {603 -- 638}, publisher = {Springer}, title = {{Multivariate Gaussians, semidefinite matrix completion, and convex algebraic geometry}}, doi = {10.1007/s10463-010-0295-4}, volume = {62}, year = {2010}, } @inproceedings{10908, abstract = {We present ABC, a software tool for automatically computing symbolic upper bounds on the number of iterations of nested program loops. The system combines static analysis of programs with symbolic summation techniques to derive loop invariant relations between program variables. Iteration bounds are obtained from the inferred invariants, by replacing variables with bounds on their greatest values. We have successfully applied ABC to a large number of examples. The derived symbolic bounds express non-trivial polynomial relations over loop variables. We also report on results to automatically infer symbolic expressions over harmonic numbers as upper bounds on loop iteration counts.}, author = {Blanc, Régis and Henzinger, Thomas A and Hottelier, Thibaud and Kovács, Laura}, booktitle = {Logic for Programming, Artificial Intelligence, and Reasoning}, editor = {Clarke, Edmund M and Voronkov, Andrei}, isbn = {9783642175107}, issn = {1611-3349}, location = {Dakar, Senegal}, pages = {103--118}, publisher = {Springer Nature}, title = {{ABC: Algebraic Bound Computation for loops}}, doi = {10.1007/978-3-642-17511-4_7}, volume = {6355}, year = {2010}, } @inproceedings{10909, abstract = {We address the problem of localizing homology classes, namely, finding the cycle representing a given class with the most concise geometric measure. We focus on the volume measure, that is, the 1-norm of a cycle. Two main results are presented. First, we prove the problem is NP-hard to approximate within any constant factor. Second, we prove that for homology of dimension two or higher, the problem is NP-hard to approximate even when the Betti number is O(1). A side effect is the inapproximability of the problem of computing the nonbounding cycle with the smallest volume, and computing cycles representing a homology basis with the minimal total volume. We also discuss other geometric measures (diameter and radius) and show their disadvantages in homology localization. Our work is restricted to homology over the ℤ2 field.}, author = {Chen, Chao and Freedman, Daniel}, booktitle = {Proceedings of the 2010 Annual ACM-SIAM Symposium on Discrete Algorithms}, location = {Austin, TX, United States}, pages = {1594--1604}, publisher = {Society for Industrial and Applied Mathematics}, title = {{Hardness results for homology localization}}, doi = {10.1137/1.9781611973075.129}, year = {2010}, } @article{11097, abstract = {The nuclear envelope (NE) is a highly regulated membrane barrier that separates the nucleus from the cytoplasm in eukaryotic cells. It contains a large number of different proteins that have been implicated in chromatin organization and gene regulation. Although the nuclear membrane enables complex levels of gene expression, it also poses a challenge when it comes to cell division. To allow access of the mitotic spindle to chromatin, the nucleus of metazoans must completely disassemble during mitosis, generating the need to re-establish the nuclear compartment at the end of each cell division. Here, I summarize our current understanding of the dynamic remodeling of the NE during the cell cycle.}, author = {HETZER, Martin W}, issn = {1943-0264}, journal = {Cold Spring Harbor Perspectives in Biology}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {3}, pages = {a000539--a000539}, publisher = {Cold Spring Harbor Laboratory}, title = {{The nuclear envelope}}, doi = {10.1101/cshperspect.a000539}, volume = {2}, year = {2010}, } @article{11098, author = {HETZER, Martin W}, issn = {1945-4589}, journal = {Aging}, keywords = {Cell Biology, Aging}, number = {2}, pages = {74--75}, publisher = {Impact Journals}, title = {{The role of the nuclear pore complex in aging of post-mitotic cells}}, doi = {10.18632/aging.100125}, volume = {2}, year = {2010}, } @article{11099, abstract = {Nuclear pore complexes (NPCs) serve as transport channels across the nuclear membrane, a double lipid bilayer that physically separates the nucleoplasm and cytoplasm of eukaryotic cells. New evidence suggests that the multiprotein nuclear pores also play a role in chromatin organization and gene expression. Given the importance of NPC function, it is not surprising that a growing list of human diseases and developmental defects have been linked to its malfunction. In order to fully understand the functional repertoire of NPCs and their essential role for nuclear organization, it is critical to determine the sequence of events that lead to the formation of nuclear pores. This is particularly relevant since NPC number, and possibly composition, are tightly linked to metabolic activity. Most of our knowledge is derived from NPC formation that occurs in dividing cells at the end of mitosis when the nuclear envelope (NE) and NPCs reform from disassembled precursors. However, NPC assembly also takes place during interphase into an intact NE. Importantly, this process is not restricted to dividing cells but also occurs during cell differentiation. Here, we will review aspects unique to this process, namely the regulation of nuclear expansion and the mechanisms of fusion between the outer and inner nuclear membranes. We will then discuss conserved and diverging mechanisms between post-mitotic and interphase assembly of the proteinaceous structure in light of recently published data.}, author = {Doucet, Christine M. and HETZER, Martin W}, issn = {1432-0886}, journal = {Chromosoma}, keywords = {Genetics (clinical), Genetics}, pages = {469--477}, publisher = {Springer Nature}, title = {{Nuclear pore biogenesis into an intact nuclear envelope}}, doi = {10.1007/s00412-010-0289-2}, volume = {119}, year = {2010}, } @article{11101, abstract = {In metazoa, nuclear pore complexes (NPCs) assemble from disassembled precursors into a reforming nuclear envelope (NE) at the end of mitosis and into growing intact NEs during interphase. Here, we show via RNAi-mediated knockdown that ELYS, a nucleoporin critical for the recruitment of the essential Nup107/160 complex to chromatin, is required for NPC assembly at the end of mitosis but not during interphase. Conversely, the transmembrane nucleoporin POM121 is critical for the incorporation of the Nup107/160 complex into new assembly sites specifically during interphase. Strikingly, recruitment of the Nup107/160 complex to an intact NE involves a membrane curvature-sensing domain of its constituent Nup133, which is not required for postmitotic NPC formation. Our results suggest that in organisms with open mitosis, NPCs assemble via two distinct mechanisms to accommodate cell cycle-dependent differences in NE topology.}, author = {Doucet, Christine M. and Talamas, Jessica A. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {6}, pages = {1030--1041}, publisher = {Elsevier}, title = {{Cell cycle-dependent differences in nuclear pore complex assembly in metazoa}}, doi = {10.1016/j.cell.2010.04.036}, volume = {141}, year = {2010}, } @article{11102, abstract = {Nuclear pore complexes have recently been shown to play roles in gene activation; however their potential involvement in metazoan transcription remains unclear. Here we show that the nucleoporins Sec13, Nup98, and Nup88, as well as a group of FG-repeat nucleoporins, bind to the Drosophila genome at functionally distinct loci that often do not represent nuclear envelope contact sites. Whereas Nup88 localizes to silent loci, Sec13, Nup98, and a subset of FG-repeat nucleoporins bind to developmentally regulated genes undergoing transcription induction. Strikingly, RNAi-mediated knockdown of intranuclear Sec13 and Nup98 specifically inhibits transcription of their target genes and prevents efficient reactivation of transcription after heat shock, suggesting an essential role of NPC components in regulating complex gene expression programs of multicellular organisms.}, author = {Capelson, Maya and Liang, Yun and Schulte, Roberta and Mair, William and Wagner, Ulrich and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {3}, pages = {372--383}, publisher = {Elsevier}, title = {{Chromatin-bound nuclear pore components regulate gene expression in higher eukaryotes}}, doi = {10.1016/j.cell.2009.12.054}, volume = {140}, year = {2010}, } @inproceedings{11753, abstract = {Ferroelectric ceramic materials have a wide range of applications because of their piezoelectric and pyroelectric properties. One of their most important physical properties is the specific heat. In this study, the specific heats of a series of lead-zirconate-titanate (PZT) compositions in the vicinity of the morphotropic phase boundary (MPB) were measured. The temperature range was from 1.8 to 300 K. It is believed that these are the lowest temperature measurements ever made on PZT. Differences between the specific heats of the different compositions were very small. However, the calculated Debye temperatures were slightly different. The results are useful in computing design parameters for technical devices.}, author = {Lang, S. B. and Lashley, J. C. and Modic, Kimberly A and Fisher, R. A. and Zhu, W. M. and Ye, Z. G.}, booktitle = {Proceedings of the 2010 IEEE International Conference on Solid Dielectrics}, issn = {2159-1687}, location = {Potsdam, Germany}, publisher = {Institute of Electrical and Electronics Engineers}, title = {{Specific heat of a ferroelectric PZT ceramic at the morphotropic phase boundary}}, doi = {10.1109/icsd.2010.5568033}, year = {2010}, } @inproceedings{11754, abstract = {Ferroelectric ceramic materials have a wide range of applications because of their piezoelectric and pyroelectric properties. One of their most important physical properties is the specific heat. In this study, the specific heats of a series of lead-zirconate-titanate (PZT) compositions in the vicinity of the morphotropic phase boundary (MPB) were measured. The temperature range was from 1.8 to 300 K. It is believed that these are the lowest temperature measurements ever made on PZT. Differences between the specific heats of the different compositions were very small. However, the calculated Debye temperatures were slightly different. The results are useful in computing design parameters for technical devices.}, author = {Lang, S.B. and Lashley, J.C. and Modic, Kimberly A and Fisher, R.A. and Zhu, W.M. and Ye, Z.G.}, booktitle = {15th IEEE Mediterranean Electrotechnical Conference}, isbn = {978-142445795-3}, location = {Valletta, Malta}, publisher = {Institute of Electrical and Electronics Engineers}, title = {{Specific heat of a ferroelectric PZT ceramic at the morphotropic phase boundary}}, doi = {10.1109/melcon.2010.5476345}, year = {2010}, } @article{8472, abstract = {Characterization of protein dynamics by solid-state NMR spectroscopy requires robust and accurate measurement protocols, which are not yet fully developed. In this study, we investigate the backbone dynamics of microcrystalline ubiquitin using different approaches. A rotational-echo double-resonance type (REDOR-type) methodology allows one to accurately measure 1H−15N order parameters in highly deuterated samples. We show that the systematic errors in the REDOR experiment are as low as 1% or even less, giving access to accurate data for the amplitudes of backbone mobility. Combining such dipolar-coupling-derived order parameters with autocorrelated and cross-correlated 15N relaxation rates, we are able to quantitate amplitudes and correlation times of backbone dynamics on picosecond and nanosecond time scales in a residue-resolved manner. While the mobility on picosecond time scales appears to have rather uniform amplitude throughout the protein, we unambiguously identify and quantitate nanosecond mobility with order parameters S2 as low as 0.8 in some regions of the protein, where nanosecond dynamics has also been revealed in solution state. The methodology used here, a combination of accurate dipolar-coupling measurements and different relaxation parameters, yields details about dynamics on different time scales and can be applied to solid protein samples such as amyloid fibrils or membrane proteins.}, author = {Schanda, Paul and Meier, Beat H. and Ernst, Matthias}, issn = {0002-7863}, journal = {Journal of the American Chemical Society}, number = {45}, pages = {15957--15967}, publisher = {American Chemical Society}, title = {{Quantitative analysis of protein backbone dynamics in microcrystalline ubiquitin by solid-state NMR spectroscopy}}, doi = {10.1021/ja100726a}, volume = {132}, year = {2010}, } @article{8473, abstract = {β2-microglobulin (β2m), the light chain of class I major histocompatibility complex, is responsible for the dialysis-related amyloidosis and, in patients undergoing long term dialysis, the full-length and chemically unmodified β2m converts into amyloid fibrils. The protein, belonging to the immunoglobulin superfamily, in common to other members of this family, experiences during its folding a long-lived intermediate associated to the trans-to-cis isomerization of Pro-32 that has been addressed as the precursor of the amyloid fibril formation. In this respect, previous studies on the W60G β2m mutant, showing that the lack of Trp-60 prevents fibril formation in mild aggregating condition, prompted us to reinvestigate the refolding kinetics of wild type and W60G β2m at atomic resolution by real-time NMR. The analysis, conducted at ambient temperature by the band selective flip angle short transient real-time two-dimensional NMR techniques and probing the β2m states every 15 s, revealed a more complex folding energy landscape than previously reported for wild type β2m, involving more than a single intermediate species, and shedding new light into the fibrillogenic pathway. Moreover, a significant difference in the kinetic scheme previously characterized by optical spectroscopic methods was discovered for the W60G β2m mutant.}, author = {Corazza, Alessandra and Rennella, Enrico and Schanda, Paul and Mimmi, Maria Chiara and Cutuil, Thomas and Raimondi, Sara and Giorgetti, Sofia and Fogolari, Federico and Viglino, Paolo and Frydman, Lucio and Gal, Maayan and Bellotti, Vittorio and Brutscher, Bernhard and Esposito, Gennaro}, issn = {0021-9258}, journal = {Journal of Biological Chemistry}, keywords = {Cell Biology, Biochemistry, Molecular Biology}, number = {8}, pages = {5827--5835}, publisher = {American Society for Biochemistry & Molecular Biology}, title = {{Native-unlike long-lived intermediates along the folding pathway of the amyloidogenic protein β2-Microglobulin revealed by real-time two-dimensional NMR}}, doi = {10.1074/jbc.m109.061168}, volume = {285}, year = {2010}, } @inbook{8506, author = {Hunt, Brian R. and Kaloshin, Vadim}, booktitle = {Handbook of Dynamical Systems}, isbn = {9780444531414}, issn = {1874-575X}, pages = {43--87}, publisher = {Elsevier}, title = {{Prevalence}}, doi = {10.1016/s1874-575x(10)00310-3}, volume = {3}, year = {2010}, } @inproceedings{8507, abstract = {We study a Cr nearly integrable Hamiltonian system defined on 𝕋3 × ℝ3. Let and µΣ1 be the restriction of Lebesgue measure on 𝕋3 × ℝ3 to ∑. We prove there is a perturbation , and an orbit (q(t), p(t)): ℝ → 𝕋3 × ℝ3 of the Hamiltonian equation such that .}, author = {Kaloshin, Vadim and ZHANG, KE and ZHENG, YONG}, booktitle = {XVIth International Congress on Mathematical Physics}, isbn = {9789814304627}, location = {Prague, Czech Republic}, pages = {314--322}, publisher = {World Scientific}, title = {{Almost dense orbit on energy surface}}, doi = {10.1142/9789814304634_0017}, year = {2010}, } @article{857, abstract = {The need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions. However, it is not known whether these restrictions impose a global limit on how far homologous protein sequences can diverge from each other. Here we explore the limits of protein evolution using sequence divergence data. We formulate a computational approach to study the rate of divergence of distant protein sequences and measure this rate for ancient proteins, those that were present in the last universal common ancestor. We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: 98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. Thus, 3.5 × 10 9 yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences.}, author = {Povolotskaya, Inna and Fyodor Kondrashov}, journal = {Nature}, number = {7300}, pages = {922 -- 926}, publisher = {Nature Publishing Group}, title = {{Sequence space and the ongoing expansion of the protein universe}}, doi = {10.1038/nature09105}, volume = {465}, year = {2010}, } @article{862, abstract = {A long-standing controversy in evolutionary biology is whether or not evolving lineages can cross valleys on the fitness landscape that correspond to low-fitness genotypes, which can eventually enable them to reach isolated fitness peaks1-9. Here we study the fitness landscapes traversed by switches between different AU and GC Watson-Crick nucleotide pairs at complementary sites of mitochondrial transfer RNA stem regions in 83 mammalian species. We find that such Watson-Crick switches occur 30-40 times more slowly than pairs of neutral substitutions, and that alleles corresponding to GU and AC non-Watson-Crick intermediate states segregate within human populations at low frequencies, similar to those of non-synonymous alleles. Substitutions leading to a Watson-Crick switch are strongly correlated, especially in mitochondrial tRNAs encoded on the GT-nucleotide-rich strand of the mitochondrial genome. Using these data we estimate that a typical Watson-Crick switch involves crossing a fitness valley of a depth of about 10-3 or even about 10-2, with AC intermediates being slightly more deleterious than GU intermediates. This compensatory evolution must proceed through rare intermediate variants that never reach fixation. The ubiquitous nature of compensatory evolution in mammalian mitochondrial tRNAs and other molecules implies that simultaneous fixation of two alleles that are individually deleterious may be a common phenomenon at the molecular level.}, author = {Meer, Margarita V and Kondrashov, Alexey S and Artzy-Randrup, Yael and Fyodor Kondrashov}, journal = {Nature}, number = {7286}, pages = {279 -- 282}, publisher = {Nature Publishing Group}, title = {{Compensatory evolution in mitochondrial tRNAs navigates valleys of low fitness}}, doi = {10.1038/nature08691}, volume = {464}, year = {2010}, } @article{872, abstract = {The rate of spontaneous mutation in natural populations is a fundamental parameter for many evolutionary phenomena. Because the rate of mutation is generally low, most of what is currently known about mutation has been obtained through indirect, complex and imprecise methodological approaches. However, in the past few years genome-wide sequencing of closely related individuals has made it possible to estimate the rates of mutation directly at the level of the DNA, avoiding most of the problems associated with using indirect methods. Here, we review the methods used in the past with an emphasis on next generation sequencing, which may soon make the accurate measurement of spontaneous mutation rates a matter of routine.}, author = {Fyodor Kondrashov and Kondrashov, Alexey S}, journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, number = {1544}, pages = {1169 -- 1176}, publisher = {Royal Society, The}, title = {{Measurements of spontaneous rates of mutations in the recent past and the near future}}, doi = {10.1098/rstb.2009.0286}, volume = {365}, year = {2010}, } @article{884, abstract = {Background: Divergence of two independently evolving sequences that originated from a common ancestor can be described by two parameters, the asymptotic level of divergence E and the rate r at which this level of divergence is approached. Constant negative selection impedes allele replacements and, therefore, is routinely assumed to decelerate sequence divergence. However, its impact on E and on r has not been formally investigated.Results: Strong selection that favors only one allele can make E arbitrarily small and r arbitrarily large. In contrast, in the case of 4 possible alleles and equal mutation rates, the lowest value of r, attained when two alleles confer equal fitnesses and the other two are strongly deleterious, is only two times lower than its value under selective neutrality.Conclusions: Constant selection can strongly constrain the level of sequence divergence, but cannot reduce substantially the rate at which this level is approached. In particular, under any constant selection the divergence of sequences that accumulated one substitution per neutral site since their origin from the common ancestor must already constitute at least one half of the asymptotic divergence at sites under such selection.Reviewers: This article was reviewed by Drs. Nicolas Galtier, Sergei Maslov, and Nick Grishin.}, author = {Kondrashov, Alexey S and Povolotskaya, Inna and Ivankov, Dmitry N and Fyodor Kondrashov}, journal = {Biology Direct}, publisher = {BioMed Central}, title = {{Rate of sequence divergence under constant selection}}, doi = {10.1186/1745-6150-5-5}, volume = {5}, year = {2010}, } @article{89, abstract = {We demonstrate the operation of a device that can produce chitosan nanoparticles in a tunable size range from 50-300 nm with small size dispersion. A piezoelectric oscillator operated at megahertz frequencies is used to aerosolize a solution containing dissolved chitosan. The solvent is then evaporated from the aerosolized droplets in a heat pipe, leaving monodisperse nanoparticles to be collected. The nanoparticle size is controlled both by the concentration of the dissolved polymer and by the size of the aerosol droplets that are created. Our device can be used with any polymer or polymer/therapeutic combination that can be prepared in a homogeneous solution and vaporized.}, author = {Wright, Ian and Higginbotham, Andrew P and Baker, Shenda and Donnelly, Tom}, journal = {ACS Applied Materials and Interfaces}, number = {8}, pages = {2360 -- 2364}, publisher = {American Chemical Society}, title = {{Generation of nanoparticles of controlled size using ultrasonic piezoelectric oscillators in solution}}, doi = {10.1021/am100375w}, volume = {2}, year = {2010}, } @article{891, abstract = {Gene duplications and their subsequent divergence play an important part in the evolution of novel gene functions. Several models for the emergence, maintenance and evolution of gene copies have been proposed. However, a clear consensus on how gene duplications are fixed and maintained in genomes is lacking. Here, we present a comprehensive classification of the models that are relevant to all stages of the evolution of gene duplications. Each model predicts a unique combination of evolutionary dynamics and functional properties. Setting out these predictions is an important step towards identifying the main mechanisms that are involved in the evolution of gene duplications.}, author = {Innan, Hideki and Fyodor Kondrashov}, journal = {Nature Reviews Genetics}, number = {2}, pages = {97 -- 108}, publisher = {Nature Publishing Group}, title = {{The evolution of gene duplications: Classifying and distinguishing between models}}, doi = {10.1038/nrg2689}, volume = {11}, year = {2010}, }