183 research outputs found

    Supreme Court Agrees to Review Design Patent Infringement Damages

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    On May 15, 2015, the United States Court of Appeals for the Federal Circuit (The Federal Circuit) handed down its decision in Apple, Inc. v. Samsung Elecs. Co. The court held that Samsungā€™s mobile phones had infringed two of Appleā€™s design patents for the iPhone series of products, D593,087, which claims some ornamental design regarding the iPhone bezel, and D604,305, which claims the ornamental design of the GUI (graphical user interface). The Federal Circuit invoked 35 U.S.C. Ā§ 289, which states: ā€œWhoever during the term of a patent for a design, without license of the owner, (1) applies the patented design, or any colorable imitation thereof, to any article of manufacture for the purpose of sale, or (2) sells or exposes for sale any article of manufacture to which such design or colorable imitation has been applied shall be liable to the owner to the extent of his total profitā€¦.ā€ This post was originally published on the Cardozo Arts & Entertainment Law Journal website on April 16, 2016. The original post can be accessed via the Archived Link button above

    Refocusing Responsibility for Dual Eligibles: Why Medicare Should Take the Lead

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    Examines the federal share of costs for those eligible for both Medicare and Medicaid, potential savings from better management of Medicare-funded care, and risks of greater state responsibility for spending. Calls for federally led efforts to cut costs

    Self-organization of stabilized microtubules by both spindle and midzone mechanisms in Xenopus egg cytosol

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    Ā© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 24 (2013): 1559-1573, doi:10.1091/mbc.E12-12-0850.Previous study of self-organization of Taxol-stabilized microtubules into asters in Xenopus meiotic extracts revealed motor-dependent organizational mechanisms in the spindle. We revisit this approach using clarified cytosol with glycogen added back to supply energy and reducing equivalents. We added probes for NUMA and Aurora B to reveal microtubule polarity. Taxol and dimethyl sulfoxide promote rapid polymerization of microtubules that slowly self-organize into assemblies with a characteristic morphology consisting of paired lines or open circles of parallel bundles. Minus ends align in NUMA-containing foci on the outside, and plus ends in Aurora Bā€“containing foci on the inside. Assemblies have a well-defined width that depends on initial assembly conditions, but microtubules within them have a broad length distribution. Electron microscopy shows that plus-end foci are coated with electron-dense material and resemble similar foci in monopolar midzones in cells. Functional tests show that two key spindle assembly factors, dynein and kinesin-5, act during assembly as they do in spindles, whereas two key midzone assembly factors, Aurora B and Kif4, act as they do in midzones. These data reveal the richness of self-organizing mechanisms that operate on microtubules after they polymerize in meiotic cytoplasm and provide a biochemically tractable system for investigating plus-end organization in midzones.Our work was funded primarily by National Institutes of Health Grant GM23928

    An Inner Centromere Protein that Stimulates the Microtubule Depolymerizing Activity of a KinI Kinesin

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    AbstractMitosis requires precise control of microtubule dynamics. The KinI kinesin MCAK, a microtubule depolymerase, is critical for this regulation. In a screen to discover previously uncharacterized microtubule-associated proteins, we identified ICIS, a protein that stimulates MCAK activity in vitro. Consistent with this biochemical property, blocking ICIS function in Xenopus extracts with antibodies caused excessive microtubule growth and inhibited spindle formation. Prior to anaphase, ICIS localized in an MCAK-dependent manner to inner centromeres, the chromosomal region located in between sister kinetochores. From Xenopus extracts, ICIS coimmunoprecipitated MCAK and the inner centromere proteins INCENP and Aurora B, which are thought to promote chromosome biorientation. By immunoelectron microscopy, we found that ICIS is present on the surface of inner centromeres, placing it in an ideal location to depolymerize microtubules associated laterally with inner centromeres. At inner centromeres, MCAK-ICIS may destabilize these microtubules and provide a mechanism that prevents kinetochore-microtubule attachment errors

    False positive probabilties for all Kepler Objects of Interest: 1284 newly validated planets and 428 likely false positives

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    We present astrophysical false positive probability calculations for every Kepler Object of Interest (KOI)---the first large-scale demonstration of a fully automated transiting planet validation procedure. Out of 7056 KOIs, we determine that 1935 have probabilities <1% to be astrophysical false positives, and thus may be considered validated planets. 1284 of these have not yet been validated or confirmed by other methods. In addition, we identify 428 KOIs likely to be false positives that have not yet been identified as such, though some of these may be a result of unidentified transit timing variations. A side product of these calculations is full stellar property posterior samplings for every host star, modeled as single, binary, and triple systems. These calculations use 'vespa', a publicly available Python package able to be easily applied to any transiting exoplanet candidate.Comment: 20 pages, 8 figures. Published in ApJ. Instructions to reproduce results can be found at https://github.com/timothydmorton/koi-fp

    XRHAMM Functions in Ran-Dependent Microtubule Nucleation and Pole Formation during Anastral Spindle Assembly

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    Background: The regulated assembly of microtubules is essential for bipolar spindle formation. Depending on cell type, microtubules nucleate through two different pathways: centrosome-driven or chromatin-driven. The chromatin-driven pathway dominates in cells lacking centrosomes.Results: Human RHAMM (receptor for hyaluronic-acid-mediated motility) was originally implicated in hyaluronic-acid-induced motility but has since been shown to associate with centrosomes and play a role in astral spindle pole integrity in mitotic systems. We have identified the Xenopus ortholog of human RHAMM as a microtubule-associated protein that plays a role in focusing spindle poles and is essential for efficient microtubule nucleation during spindle assembly without centrosomes. XRHAMM associates both with Ī³-TuRC, a complex required for microtubule nucleation and with TPX2, a protein required for microtubule nucleation and spindle pole organization.Conclusions: XRHAMM facilitates Ran-dependent, chromatin-driven nucleation in a process that may require coordinate activation of TPX2 and Ī³-TuRC

    Cell polarization during monopolar cytokinesis

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    During cytokinesis, a specialized set of proteins is recruited to the equatorial region between spindle poles by microtubules and actin filaments, enabling furrow assembly and ingression before cell division. We investigate the mechanisms underlying regional specialization of the cytoskeleton in HeLa cells undergoing drug-synchronized monopolar cytokinesis. After forced mitotic exit, the cytoskeleton of monopolar mitotic cells is initially radially symmetric but undergoes a symmetry-breaking reaction that simultaneously polarizes microtubules and the cell cortex, with a concentration of cortical furrow markers into a cap at one side of the cell. Polarization requires microtubules, F-actin, RhoA, Myosin II activity, and Aurora B kinase activity. Aurora B localizes to actin cables in a gap between the monopolar midzone and the furrow-like cortex, suggesting a communication between them. We propose that feedback loops between cortical furrow components and microtubules promote symmetry breaking during monopolar cytokinesis and regional specialization of the cytoskeleton during normal bipolar cytokinesis

    Reassembly of contractile actin cortex in cell blebs

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    Contractile actin cortex is involved in cell morphogenesis, movement, and cytokinesis, but its organization and assembly are poorly understood. During blebbing, the membrane detaches from the cortex and inflates. As expansion ceases, contractile cortex reassembles under the membrane and drives bleb retraction. This cycle enabled us to measure the temporal sequence of protein recruitment to the membrane during cortex reassembly and to explore dependency relationships. Expanding blebs were devoid of actin, but proteins of the erythrocytic submembranous cytoskeleton were present. When expansion ceased, ezrin was recruited to the membrane first, followed by actin, actin-bundling proteins, and, finally, contractile proteins. Complete assembly of the contractile cortex, which was organized into a cagelike mesh of filaments, took āˆ¼30 s. Cytochalasin D blocked recruitment of actin and Ī±-actinin, but had no effect on membrane association of ankyrin B and ezrin. Ezrin played no role in actin nucleation, but was essential for tethering the membrane to the cortex. The Rho pathway was important for cortex assembly in blebs

    Direct observation of microtubule dynamics at kinetochores in Xenopus extract spindles: implications for spindle mechanics

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    Microtubule plus ends dynamically attach to kinetochores on mitotic chromosomes. We directly imaged this dynamic interface using high resolution fluorescent speckle microscopy and direct labeling of kinetochores in Xenopus extract spindles. During metaphase, kinetochores were stationary and under tension while plus end polymerization and poleward microtubule flux (flux) occurred at velocities varying from 1.5ā€“2.5 Ī¼m/min. Because kinetochore microtubules polymerize at metaphase kinetochores, the primary source of kinetochore tension must be the spindle forces that produce flux and not a kinetochore-based mechanism. We infer that the kinetochore resists translocation of kinetochore microtubules through their attachment sites, and that the polymerization state of the kinetochore acts a ā€œslip-clutchā€ mechanism that prevents detachment at high tension. At anaphase onset, kinetochores switched to depolymerization of microtubule plus ends, resulting in chromosome-to-pole rates transiently greater than flux. Kinetochores switched from persistent depolymerization to persistent polymerization and back again during anaphase, bistability exhibited by kinetochores in vertebrate tissue cells. These results provide the most complete description of spindle microtubule poleward flux to date, with important implications for the microtubuleā€“kinetochore interface and for how flux regulates kinetochore function
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