416 research outputs found

    The Effect of Anesthetics on Living Cells

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    Power Wheelchair Canopy

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    Some power wheelchair users can not drive and independently hold an umbrella at the time because they do not have much upper body strength. Therefore, users are unprotected from the rain and are getting soaking wet. One of the members of this group is in a wheelchair and faces this problem. He has previously searched for something to protect him from rain, but could not found something he could independently use. What users need is a powered umbrella that attaches to their power wheelchair. There is no such umbrella available in the market. In this project, the solution to this problem will be designed and built in the form of an umbrella for his wheelchair. Exploration of various methods of rain protect will be explored. Calculations will be performed to verify that everything will work when assembled. The prototype will then be built. Assuming there will be some issues, as there always seem to be, several iterations of the prototype will be built. This is assuming that there will still be money left in the budget to complete these other iterations. It is also desired to make it inexpensive. This will allow power wheelchair users all over the world to purchase it for themselves. In order to achieve this, the project will lean heavily on the 3-D printing capabilities that the University of Akron has to offer

    Reliability and validity of cross-national homicide data: A comparison of UN and WHO data

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    Data reliability and validity are major methodological concerns in cross-national analyses of crime. Despite the large literature on cross-national homicide rates, there is little agreement on which source of data provides the most reliable estimates. In addition, few studies have examined the potential threat to validity posed by unclassified deaths. Through a description of trends over time as well as multivariate analyses, the current study aims to shed some light on these questions by (1) assessing the reliability of cross-national homicide data from the United Nations and the World Health Organization, and (2) investigating the impact of unclassified deaths on the validity of WHO data. Findings indicate that UN and WHO homicide rates (n=56) differ in magnitude but produce similar outcomes. Drawing on well-known correlates of cross-national homicide rates, the UN data provide more robust results and produce statistical models with less error. We find that WHO data are more stable and reliable over time, and better suited for longitudinal analyses. Findings also suggest that analyses drawing on WHO homicide data should not disregard unclassified deaths because their inclusion produces better fitted statistical models and provides a closer estimate of the true number of homicides

    Helical Chirality: a Link between Local Interactions and Global Topology in DNA

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    DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

    A-Site Residues Move Independently from P-Site Residues in all-Atom Molecular Dynamics Simulations of the 70S Bacterial Ribosome

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    The ribosome is a large macromolecular machine, and correlated motion between residues is necessary for coordinating function across multiple protein and RNA chains. We ran two all-atom, explicit solvent molecular dynamics simulations of the bacterial ribosome and calculated correlated motion between residue pairs by using mutual information. Because of the short timescales of our simulation (ns), we expect that dynamics are largely local fluctuations around the crystal structure. We hypothesize that residues that show coupled dynamics are functionally related, even on longer timescales. We validate our model by showing that crystallographic B-factors correlate well with the entropy calculated as part of our mutual information calculations. We reveal that A-site residues move relatively independently from P-site residues, effectively insulating A-site functions from P-site functions during translation

    Topoisomerase IIΞ± Binding Domains of Adenomatous Polyposis Coli Influence Cell Cycle Progression and Aneuploidy

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    Truncating mutations in the tumor suppressor gene APC (Adenomatous Polyposis Coli) are thought to initiate the majority of colorectal cancers. The 15- and 20-amino acid repeat regions of APC bind beta-catenin and have been widely studied for their role in the negative regulation of canonical Wnt signaling. However, functions of APC in other important cellular processes, such as cell cycle control or aneuploidy, are only beginning to be studied. Our previous investigation implicated the 15-amino acid repeat region of APC (M2-APC) in the regulation of the G2/M cell cycle transition through interaction with topoisomerase IIalpha (topo IIalpha).We now demonstrate that the 20-amino acid repeat region of APC (M3-APC) also interacts with topo IIalpha in colonic epithelial cells. Expression of M3-APC in cells with full-length endogenous APC causes cell accumulation in G2. However, cells with a mutated topo IIalpha isoform and lacking topo IIbeta did not arrest, suggesting that the cellular consequence of M2- or M3-APC expression depends on functional topoisomerase II. Both purified recombinant M2- and M3-APC significantly enhanced the activity of topo IIalpha. Of note, although M3-APC can bind beta-catenin, the G2 arrest did not correlate with beta-catenin expression or activity, similar to what was seen with M2-APC. More importantly, expression of either M2- or M3-APC also led to increased aneuploidy in cells with full-length endogenous APC but not in cells with truncated endogenous APC that includes the M2-APC region.Together, our data establish that the 20-amino acid repeat region of APC interacts with topo IIalpha to enhance its activity in vitro, and leads to G2 cell cycle accumulation and aneuploidy when expressed in cells containing full-length APC. These findings provide an additional explanation for the aneuploidy associated with many colon cancers that possess truncated APC

    Deletion of Forkhead Box M1 Transcription Factor from Respiratory Epithelial Cells Inhibits Pulmonary Tumorigenesis

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    The Forkhead Box m1 (Foxm1) protein is induced in a majority of human non-small cell lung cancers and its expression is associated with poor prognosis. However, specific requirements for the Foxm1 in each cell type of the cancer lesion remain unknown. The present study provides the first genetic evidence that the Foxm1 expression in respiratory epithelial cells is essential for lung tumorigenesis. Using transgenic mice, we demonstrated that conditional deletion of Foxm1 from lung epithelial cells (epFoxm1βˆ’/βˆ’ mice) prior to tumor initiation caused a striking reduction in the number and size of lung tumors, induced by either urethane or 3-methylcholanthrene (MCA)/butylated hydroxytoluene (BHT). Decreased lung tumorigenesis in epFoxm1βˆ’/βˆ’ mice was associated with diminished proliferation of tumor cells and reduced expression of Topoisomerase-2Ξ± (TOPO-2Ξ±), a critical regulator of tumor cell proliferation. Depletion of Foxm1 mRNA in cultured lung adenocarcinoma cells significantly decreased TOPO-2Ξ± mRNA and protein levels. Moreover, Foxm1 directly bound to and induced transcription of the mouse TOPO-2Ξ± promoter region, indicating that TOPO-2Ξ± is a direct target of Foxm1 in lung tumor cells. Finally, we demonstrated that a conditional deletion of Foxm1 in pre-existing lung tumors dramatically reduced tumor growth in the lung. Expression of Foxm1 in respiratory epithelial cells is critical for lung cancer formation and TOPO-2Ξ± expression in vivo, suggesting that Foxm1 is a promising target for anti-tumor therapy
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