Symbolic Manipulators Affect Mathematical Mindsets

Symbolic calculators like Mathematica are becoming more commonplace among upper level physics students. The presence of such a powerful calculator can couple strongly to the type of mathematical reasoning students employ. It does not merely offer a convenient way to perform the computations students would have otherwise wanted to do by hand. This paper presents examples from the work of upper level physics majors where Mathematica plays an active role in focusing and sustaining their thought around calculation. These students still engage in powerful mathematical reasoning while they calculate but struggle because of the narrowed breadth of their thinking. Their reasoning is drawn into local attractors where they look to calculation schemes to resolve questions instead of, for example, mapping the mathematics to the physical system at hand. We model the influence of Mathematica as an integral part of the constant feedback that occurs in how students frame, and hence focus, their work

Nuclear matrix proteins distinguish normal diploid osteoblasts from osteosarcoma cells

Interrelationships between nuclear architecture and gene expression were examined by comparing the representation of nuclear matrix proteins in ROS 17/2.8 rat and MG-63 human osteosarcoma cells with those in normal diploid osteoblasts. The tumor-derived cells coexpress genes which are expressed in a sequential and mutually exclusive manner during the progressive stages of osteoblast differentiation. In osteosarcoma cells two-dimensional electrophoretic analysis indicates a composite representation of nuclear matrix proteins characteristic of both the proliferative and postproliferative periods of osteoblast phenotype development. In addition, nuclear matrix proteins unique to the tumor cells and the absence of nuclear matrix proteins found only in normal diploid osteoblasts are observed. Tumor-specific nuclear matrix proteins include those expressed in a proliferation-dependent and independent manner. There is a parallel relationship between nuclear matrix proteins and the expression of cell growth and tissue-specific genes during osteoblast differentiation and in osteosarcoma cells where the developmental sequence of gene expression has been abrogated. Nuclear matrix proteins therefore provide markers reflecting defined periods of bone cell differentiation and phenotypic characteristics of an osteosarcoma

Taking the Measure of the Universe: Precision Astrometry with SIM PlanetQuest

Precision astrometry at microarcsecond accuracy has application to a wide range of astrophysical problems. This paper is a study of the science questions that can be addressed using an instrument that delivers parallaxes at about 4 microarcsec on targets as faint as V = 20, differential accuracy of 0.6 microarcsec on bright targets, and with flexible scheduling. The science topics are drawn primarily from the Team Key Projects, selected in 2000, for the Space Interferometry Mission PlanetQuest (SIM PlanetQuest). We use the capabilities of this mission to illustrate the importance of the next level of astrometric precision in modern astrophysics. SIM PlanetQuest is currently in the detailed design phase, having completed all of the enabling technologies needed for the flight instrument in 2005. It will be the first space-based long baseline Michelson interferometer designed for precision astrometry. SIM will contribute strongly to many astronomical fields including stellar and galactic astrophysics, planetary systems around nearby stars, and the study of quasar and AGN nuclei. SIM will search for planets with masses as small as an Earth orbiting in the `habitable zone' around the nearest stars using differential astrometry, and could discover many dozen if Earth-like planets are common. It will be the most capable instrument for detecting planets around young stars, thereby providing insights into how planetary systems are born and how they evolve with time. SIM will observe significant numbers of very high- and low-mass stars, providing stellar masses to 1%, the accuracy needed to challenge physical models. Using precision proper motion measurements, SIM will probe the galactic mass distribution and the formation and evolution of the Galactic halo. (abridged)Comment: 54 pages, 28 figures, uses emulateapj. Submitted to PAS

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Phylogenetic occurrence of coiled coil proteins: implications for tissue structure in metazoa via a coiled coil tissue matrix

We examined GenBank sequence files with a heptad repeat analysis program to assess the phylogenetic occurrence of coiled coil proteins, how heptad repeat domains are organized within them, and what structural/functional categories they comprise. Of 102,007 proteins analyzed, 5.95% (6,074) contained coiled coil domains; 1.26% (1,289) contained extended (\u3e 75 amino acid) domains. While the frequency of proteins containing coiled coils was surprisingly constant among all biota, extended coiled coil proteins were fourfold more frequent in the animal kingdom and may reflect early events in the divergence of plants and animals. Structure/function categories of extended coils also revealed phylogenetic differences. In pathogens and parasites, many extended coiled coil proteins are external and bind host proteins. In animals, the majority of extended coiled coil proteins were identified as constituents of two protein categories: 1) myosins and motors; or 2) components of the nuclear matrix-intermediate filament scaffold. This scaffold, produced by sequential extraction of epithelial monolayers in situ, contains only 1-2% of the cell mass while accurately retaining morphological features of living epithelium and is greatly enriched in proteins with extensive, interrupted coiled coil forming domains. The increased occurrence of this type of protein in metazoa compared with plants or protists leads us to hypothesize a tissue-wide matrix of coiled coil interactions underlying metazoan differentiated cell and tissue structure

Phosphorylation of NUMA occurs during nuclear breakdown and not mitotic spindle assembly

NuMA, the nuclear mitotic apparatus protein, is a component of the nuclear matrix at interphase that redistributes to the spindle poles at mitosis. While the function of NuMA is not known, it has been implicated in spindle organization during mitosis and nuclear reformation. Phosphorylation is thought to play a regulatory role in NuMA function. In this study, NuMA phosphorylation was examined through the cell cycle using highly synchronized cells. In intact cells labeled with 32P-orthophosphate, NuMA appeared as a 250 kDa phosphoprotein in interphase that shifted to a higher apparent molecular mass in mitosis. The shift was due to phosphorylation as shown by reduction of the shifted band to interphase mobility by phosphatase treatment. This phosphorylation event occurred roughly at the G2/M transition at the time of NuMA\u27s release from the nucleus and its redistribution to the mitotic spindle. However, mitotic phosphorylation did not require spindle formation since the phosphorylated species was detected in nocodazole-treated cells lacking microtubule spindles. Dephosphorylation of NuMA occurred in two distinct steps, after lamin B assembled into the nuclear lamina, in early G1 and at the end of G1. Based on the timing of the phosphorylation and dephosphorylation observed in this study, we propose that they may play a role in nuclear events such as nuclear organization, transcription, or initiation of DNA replication at G1/S

Product of the oncogene-activating gene Tpr is a phosphorylated protein of the nuclear pore complex

We have identified a component of the human nuclear pore complex and have shown that it is the product of a gene involved in oncogenic activation. A monoclonal antibody raised against purified nuclear matrix proteins recognizes a single protein with an electrophoretic mobility of approximately 300 kDa and stains the nuclear envelope in a punctate pattern typical of nuclear pores. The antibody was used to screen lambda gt11 human cDNA libraries, and the resulting clones were sequenced and compared to sequences in the Genbank database. An exact match was found with the human tpr (for translocated promoter region) gene, a gene shown previously to be involved in the oncogenic activation of several protein kinases. Double-label immunofluorescent microscopy with the anti-Tpr antibody and an antibody to the previously characterized nuclear pore complex protein nup153 confirms that Tpr is localized to the nuclear pore complex. Tpr is located on the cytoplasmic face of the nucleus, as demonstrated by immunofluorescent staining of cells permeabilized with digitonin. Tpr is a 2,349-amino acid protein with extensive coiled-coil domains and an acidic globular C-terminus. The protein contains 10 leucine zipper motifs and numerous sites for phosphorylation by a variety of protein kinases. Immunoprecipitation of Tpr from 32P-orthophosphate-labeled cells shows that it is a phosphoprotein. Potential functions for Tpr and possible mechanisms for the transforming activity of Tpr fusion proteins are discussed