250 research outputs found

    Single microtubules and small networks become significantly stiffer on short time-scales upon mechanical stimulation

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    The transfer of mechanical signals through cells is a complex phenomenon. To uncover a new mechanotransduction pathway, we study the frequency-dependent transport of mechanical stimuli by single microtubules and small networks in a bottom-up approach using optically trapped beads as anchor points. We interconnected microtubules to linear and triangular geometries to perform micro-rheology by defined oscillations of the beads relative to each other. We found a substantial stiffening of single filaments above a characteristic transition frequency of 1-30 Hz depending on the filament's molecular composition. Below this frequency, filament elasticity only depends on its contour and persistence length. Interestingly, this elastic behavior is transferable to small networks, where we found the surprising effect that linear two filament connections act as transistor-like, angle dependent momentum filters, whereas triangular networks act as stabilizing elements. These observations implicate that cells can tune mechanical signals by temporal and spatial filtering stronger and more flexibly than expected

    Massive autophosphorylation of the Ser/Thr-rich domain controls protein kinase activity of TRPM6 and TRPM7.

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    TRPM6 and TRPM7 are bifunctional proteins expressing a TRP channel fused to an atypical alpha-kinase domain. While the gating properties of TRPM6 and TRPM7 channels have been studied in detail, little is known about the mechanisms regulating kinase activity. Recently, we found that TRPM7 associates with its substrate myosin II via a kinase-dependent mechanism suggesting a role for autophosphorylation in substrate recognition. Here, we demonstrate that the cytosolic C-terminus of TRPM7 undergoes massive autophosphorylation (32+/-4 mol/mol), which strongly increases the rate of substrate phosphorylation. Phosphomapping by mass spectrometry indicates that the majority of autophosphorylation sites (37 out of 46) map to a Ser/Thr-rich region immediately N-terminal of the catalytic domain. Deletion of this region prevents substrate phosphorylation without affecting intrinsic catalytic activity suggesting that the Ser/Thr-rich domain contributes to substrate recognition. Surprisingly, the TRPM6-kinase is regulated by an analogous mechanism despite a lack of sequence conservation with the TRPM7 Ser/Thr-rich domain. In conclusion, our findings support a model where massive autophosphorylation outside the catalytic domain of TRPM6 and TRPM7 may facilitate kinase-substrate interactions leading to enhanced phosphorylation of those substrates

    The Gallery \u2715

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    This is a digital copy of the print book produced by the Gallery 2015 team. Contents: Preface p. 6, Core Studios p. 8, Graphic Design p. 20, Illustration p. 32, Painting p. 44, Printmaking p. 56, Metals & Jewelry p. 68, Ceramics p. 80, Sculpture p. 92, 3D Biomedical p. 104, Photography p. 116, Credits p. 128, Artist Index p. 130. Files for individual sections may be viewed on the detailed metadata page by clicking on the book title.https://rdw.rowan.edu/the_gallery/1001/thumbnail.jp

    On the Possibility of Superluminal Neutrino Propagation

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    We analyze the possibility of superluminal neutrino propagation delta v = (v - c)/c > 0 as indicated by OPERA data, in view of previous phenomenological constraints from supernova SN1987a and gravitational Cerenkov radiation. We argue that the SN1987a data rule out delta v ~ (E_\nu/M_N)^N for N \le 2 and exclude, in particular, a Lorentz-invariant interpretation in terms of a 'conventional' tachyonic neutrino. We present two toy Lorentz-violating theoretical models, one a Lifshitz-type fermion model with superluminality depending quadratically on energy, and the other a Lorentz-violating modification of a massless Abelian gauge theory with axial-vector couplings to fermions. In the presence of an appropriate background field, fermions may propagate superluminally or subluminally, depending inversely on energy, and on direction. Reconciling OPERA with SN1987a would require this background field to depend on location.Comment: 15 pages, replacement has an expanded and revised version of the second model; Notes added on how this model evades the Cohen-Glashow constraint

    The Vehicle, Fall 2002

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    Table of Contents Caterpillar DreamsAubrey Bonannopage 4 GrandmotherNatalie Espositopage 5 PhotographNatalie Espositopage 5 For My SisterAnn Hudsonpage 6 BuckeyeCaleb Judypage 6 A Moment\u27s GlowMelissa Knoblockpage 7 April 8,1994Andy Kochpage 8 Koch FuneralsAndy Kochpage 9 Grandpa Koch\u27s Sense of HumorAndy Kochpage 10 DeparturesDave Moutraypage 11 1958 VetteAlex Nicolpage 11 HomelandDave Moutraypage 12 The TravelerDave Moutraypage 12 GrandpaJennifer Probstpage 13 Confusion upon LearningJody Sanchezpage 14 Chucktown PrideMike Scalespage 14 I Might be WrongDallas Schumacherpage 15-20 UntitledAlex Nicholpage 21 Late NightRachel Seftonpage 22 Old DreamsRachel Seftonpage 23 Two-Minded ThoughtsRachel Sefton & Jodi Sanchezpage 24 Strange GraffitiMike Scalespage 24 On PoetryNick Slicerpage 25-26 Sometimes Things Just Happen That WayThomas Webbpage 26-33 Biographiespage 34-35 Editor\u27s Notepage 36https://thekeep.eiu.edu/vehicle/1076/thumbnail.jp

    Dried blood spot UHPLC-MS/MS analysis of oseltamivir and oseltamivircarboxylate-a validated assay for the clinic

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    The neuraminidase inhibitor oseltamivir (Tamiflu®) is currently the first-line therapy for patients with influenza virus infection. Common analysis of the prodrug and its active metabolite oseltamivircarboxylate is determined via extraction from plasma. Compared with these assays, dried blood spot (DBS) analysis provides several advantages, including a minimum sample volume required for the measurement of drugs in whole blood. Samples can easily be obtained via a simple, non-invasive finger or heel prick. Mainly, these characteristics make DBS an ideal tool for pediatrics and to measure multiple time points such as those needed in therapeutic drug monitoring or pharmacokinetic studies. Additionally, DBS sample preparation, stability, and storage are usually most convenient. In the present work, we developed and fully validated a DBS assay for the simultaneous determination of oseltamivir and oseltamivircarboxylate concentrations in human whole blood. We demonstrate the simplicity of DBS sample preparation, and a fast, accurate and reproducible analysis using ultra high-performance liquid chromatography coupled to a triple quadrupole mass spectrometer. A thorough validation on the basis of the most recent FDA guidelines for bioanalytical method validation showed that the method is selective, precise, and accurate (≤15% RSD), and sensitive over the relevant clinical range of 5-1,500 ng/mL for oseltamivir and 20-1,500 ng/mL for the oseltamivircarboxyl

    Risk for Clostridium difficile Infection after Radical Cystectomy for Bladder Cancer: Analysis of a Contemporary Series

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    Introduction This study seeks to evaluate the incidence and associated risk factors of Clostridium difficile infection (CDI) in patients undergoing radical cystectomy (RC) for bladder cancer. Methods We retrospectively reviewed a single institution׳s bladder cancer database including all patients who underwent RC between 2010 and 2013. CDI was diagnosed by detection of Clostridium difficile toxin B gene using polymerase chain reaction–based stool assay in patients with clinically significant diarrhea within 90 days of the index operation. A multivariable logistic regression model was used to identify demographics and perioperative factors associated with developing CDI. Results Of the 552 patients who underwent RC, postoperative CDI occurred in 49 patients (8.8%) with a median time to diagnosis after RC of 7 days (interquartile range: 5–19). Of the 122 readmissions for postoperative complications, 10% (n = 12) were related to CDI; 2 patients died of sepsis directly related to severe CDI. On multivariate logistic regression, the use of chronic antacid therapy (odds ratio = 1.9, 95% CI: 1.02–3.68, P = 0.04) and antibiotic exposure greater than 7 days (odds ratio = 2.2, 95% CI: 1.11–4.44, P = 0.02) were independently associated with developing CDI. The use of preoperative antibiotics for positive findings on urine culture within 30 days before surgery was not statistically significantly associated with development of CDI (P = 0.06). Conclusions The development of CDI occurs in 8.8% of patients undergoing RC. Our study demonstrates that use of chronic antacid therapy and long duration of antimicrobial exposure are associated with development of CDI. Efforts focusing on minimizing antibiotic exposure in patients undergoing RC are needed, and perioperative antimicrobial prophylaxis guidelines should be followed

    Improving Measurement of Forest Structural Parameters by Co-Registering of High Resolution Aerial Imagery and Low Density LiDAR Data

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    Forest structural parameters, such as tree height and crown width, are indispensable for evaluating forest biomass or forest volume. LiDAR is a revolutionary technology for measurement of forest structural parameters, however, the accuracy of crown width extraction is not satisfactory when using a low density LiDAR, especially in high canopy cover forest. We used high resolution aerial imagery with a low density LiDAR system to overcome this shortcoming. A morphological filtering was used to generate a DEM (Digital Elevation Model) and a CHM (Canopy Height Model) from LiDAR data. The LiDAR camera image is matched to the aerial image with an automated keypoints search algorithm. As a result, a high registration accuracy of 0.5 pixels was obtained. A local maximum filter, watershed segmentation, and object-oriented image segmentation are used to obtain tree height and crown width. Results indicate that the camera data collected by the integrated LiDAR system plays an important role in registration with aerial imagery. The synthesis with aerial imagery increases the accuracy of forest structural parameter extraction when compared to only using the low density LiDAR data
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