Rheological Chaos in a Scalar Shear-Thickening Model

We study a simple scalar constitutive equation for a shear-thickening material at zero Reynolds number, in which the shear stress \sigma is driven at a constant shear rate \dot\gamma and relaxes by two parallel decay processes: a nonlinear decay at a nonmonotonic rate R(\sigma_1) and a linear decay at rate \lambda\sigma_2. Here \sigma_{1,2}(t) = \tau_{1,2}^{-1}\int_0^t\sigma(t')\exp[-(t-t')/\tau_{1,2}] {\rm d}t' are two retarded stresses. For suitable parameters, the steady state flow curve is monotonic but unstable; this arises when \tau_2>\tau_1 and 0>R'(\sigma)>-\lambda so that monotonicity is restored only through the strongly retarded term (which might model a slow evolution of material structure under stress). Within the unstable region we find a period-doubling sequence leading to chaos. Instability, but not chaos, persists even for the case \tau_1\to 0. A similar generic mechanism might also arise in shear thinning systems and in some banded flows.Comment: Reference added; typos corrected. To appear in PRE Rap. Com

Lysosomotropic Properties of Weakly Basic Anticancer Agents Promote Cancer Cell Selectivity In Vitro

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Drug distribution in cells is a fundamentally important, yet often overlooked, variable in drug efficacy. Many weakly basic anticancer agents accumulate extensively in the acidic lysosomes of normal cells through ion trapping. Lysosomal trapping reduces the activity of anticancer drugs, since anticancer drug targets are often localized in the cell cytosol or nucleus. Some cancer cells have defective acidification of lysosomes, which causes a redistribution of trapped drugs from the lysosomes to the cytosol. We have previously established that such differences in drug localization between normal and cancer cells can contribute to the apparent selectivity of weakly basic drugs to cancer cells in vitro. In this work, we tested whether this intracellular distribution-based drug selectivity could be optimized based on the acid dissociation constant (pKa) of the drug, which is one of the determinants of lysosomal sequestration capacity. We synthesized seven weakly basic structural analogs of the Hsp90 inhibitor geldanamycin (GDA) with pKa values ranging from 5 to 12. The selectivity of each analog was expressed by taking ratios of anti-proliferative IC50 values of the inhibitors in normal fibroblasts to the IC50 values in human leukemic HL-60 cells. Similar selectivity assessments were performed in a pair of cancer cell lines that differed in lysosomal pH as a result of siRNA-mediated alteration of vacuolar proton ATPase subunit expression. Optimal selectivity was observed for analogs with pKa values near 8. Similar trends were observed with commercial anticancer agents with varying weakly basic pKa values. These evaluations advance our understanding of how weakly basic properties can be optimized to achieve maximum anticancer drug selectivity towards cancer cells with defective lysosomal acidification in vitro. Additional in vivo studies are needed to examine the utility of this approach for enhancing selectivity

Detection of fractures of hand and forearm in whole-body CT for suspected polytrauma in intubated patients

Background: The aim of this study was to evaluate the potential of whole-body CT for diagnosis of hand and forearm fractures in intubated patients with suspected polytrauma. Methods: We performed a retrospective analysis on data collected from two trauma centres in Germany, including demographics, ISS, clinical symptoms, depiction in whole-body CT, and time to diagnosis. Results: Out of 426 patients included in the study, 66 (15.5%) suffered a hand or forearm fracture. The total number of fractures was 132, the whole-body CT report mentioned 98 (74.2%). 16 (12,1%) fractures of 12 patients were diagnosed later than 24 h after admission. Late diagnoses of fractures of the hand occurred more often if the hand was not fully included in the CT scan field. The sensitivity of whole-body CT for cases with fractures of hand and/or forearm with full inclusion of the corresponding area in the scan field was 80.2%. Conclusions: This study shows that whole-body CT is a valuable diagnostic tool for hand fractures in polytrauma patients. Hands should be evaluated regardless of clinical presentation in intubated patients after suspected polytrauma if they are included in the whole-body CT. © 2020 The Author(s)

PANIC: the new panoramic NIR camera for Calar Alto

PANIC is a wide-field NIR camera, which is currently under development for the Calar Alto observatory (CAHA) in Spain. It uses a mosaic of four Hawaii-2RG detectors and covers the spectral range from 0.8-2.5 micron(z to K-band). The field-of-view is 30x30 arcmin. This instrument can be used at the 2.2m telescope (0.45arcsec/pixel, 0.5x0.5 degree FOV) and at the 3.5m telescope (0.23arcsec/pixel, 0.25x0.25 degree FOV). The operating temperature is about 77K, achieved by liquid Nitrogen cooling. The cryogenic optics has three flat folding mirrors with diameters up to 282 mm and nine lenses with diameters between 130 mm and 255 mm. A compact filter unit can carry up to 19 filters distributed over four filter wheels. Narrow band (1%) filters can be used. The instrument has a diameter of 1.1 m and it is about 1 m long. The weight limit of 400 kg at the 2.2m telescope requires a light-weight cryostat design. The aluminium vacuum vessel and radiation shield have wall thicknesses of only 6 mm and 3 mm respectively.Comment: This paper has been presented in the SPIE of Astronomical Telescopes and Instrumentation 2008 in Marseille (France

Aging (Albany NY)

The combination of functional genomics with next generation sequencing facilitates new experimental strategies for addressing complex biological phenomena. Here, we report the identification of a gain-of-function allele of peroxiredoxin (thioredoxin peroxidase, Tsa1p) via whole-genome re-sequencing of a dominantSaccharomyces cerevisiae mutant obtained by chemical mutagenesis. Yeast strain K6001, a screening system for lifespan phenotypes, was treated with ethyl methanesulfonate (EMS). We isolated an oxidative stress-resistant mutant (B7) which transmitted this phenotype in a background-independent, monogenic and dominant way. By massive parallel pyrosequencing, we generated an 38.8 fold whole-genome coverage of the strains, which differed in 12,482 positions from the reference (S288c) genome. Via a subtraction strategy, we could narrow this number to 13 total and 4 missense nucleotide variations that were specific for the mutant. Via expression in wild type backgrounds, we show that one of these mutations, exchanging a residue in the peroxiredoxin Tsa1p, was responsible for the mutant phenotype causing background-independent dominant oxidative stress-resistance. These effects were not provoked by altered Tsa1p levels, nor could they be simulated by deletion, haploinsufficiency or over-expression of the wild-type allele. Furthermore, via both a mother-enrichment technique and a micromanipulation assay, we found a robust premature aging phenotype of this oxidant-resistant strain. Thus, TSA1-B7 encodes for a novel dominant form of peroxiredoxin, and establishes a new connection between oxidative stress and aging. In addition, this study shows that the re-sequencing of entire genomes is becoming a promising alternative for the identification of functional alleles in approaches of classic molecular genetics

Optimal acquisition scheme for flow-compensated intravoxel incoherent motion diffusion-weighted imaging in the abdomen: An accurate and precise clinically feasible protocol.

Purpose Flow-compensated (FC) diffusion-weighted MRI (DWI) for intravoxel-incoherent motion (IVIM) modeling allows for a more detailed description of tissue microvasculature than conventional IVIM. The long acquisition time of current FC-IVIM protocols, however, has prohibited clinical application. Therefore, we developed an optimized abdominal FC-IVIM acquisition with a clinically feasible scan time.Methods Precision and accuracy of the FC-IVIM parameters were assessed by fitting the FC-IVIM model to signal decay curves, simulated for different acquisition schemes. Diffusion-weighted acquisitions were added subsequently to the protocol, where we chose the combination of b-value, diffusion time and gradient profile (FC or bipolar) that resulted in the largest improvement to its accuracy and precision. The resulting two optimized FC-IVIM protocols with 25 and 50 acquisitions (FC-IVIMopt25 and FC-IVIMopt50 ), together with a complementary acquisition consisting of 50 diffusion-weighting (FC-IVIMcomp ), were acquired in repeated abdominal free-breathing FC-IVIM imaging of seven healthy volunteers. Intersession and intrasession within-subject coefficient of variation of the FC-IVIM parameters were compared for the liver, spleen, and kidneys.Results Simulations showed that the performance of FC-IVIM improved in tissue with larger perfusion fraction and signal-to-noise ratio. The scan time of the FC-IVIMopt25 and FC-IVIMopt50 protocols were 8 and 16 min. The best in vivo performance was seen in FC-IVIMopt50 . The intersession within-subject coefficients of variation of FC-IVIMopt50 were 11.6%, 16.3%, 65.5%, and 36.0% for FC-IVIM model parameters diffusivity, perfusion fraction, characteristic time and blood flow velocity, respectively.Conclusions We have optimized the FC-IVIM protocol, allowing for clinically feasible scan times (8-16 min)

GRAVITY: getting to the event horizon of Sgr A*

We present the second-generation VLTI instrument GRAVITY, which currently is in the preliminary design phase. GRAVITY is specifically designed to observe highly relativistic motions of matter close to the event horizon of Sgr A*, the massive black hole at center of the Milky Way. We have identified the key design features needed to achieve this goal and present the resulting instrument concept. It includes an integrated optics, 4-telescope, dual feed beam combiner operated in a cryogenic vessel; near infrared wavefront sensing adaptive optics; fringe tracking on secondary sources within the field of view of the VLTI and a novel metrology concept. Simulations show that the planned design matches the scientific needs; in particular that 10 microarcsecond astrometry is feasible for a source with a magnitude of K=15 like Sgr A*, given the availability of suitable phase reference sources.Comment: 13 pages, 11 figures, to appear in the conference proceedings of SPIE Astronomical Instrumentation, 23-28 June 2008, Marseille, Franc

An overview of the mid-infrared spectro-interferometer MATISSE: science, concept, and current status

MATISSE is the second-generation mid-infrared spectrograph and imager for the Very Large Telescope Interferometer (VLTI) at Paranal. This new interferometric instrument will allow significant advances by opening new avenues in various fundamental research fields: studying the planet-forming region of disks around young stellar objects, understanding the surface structures and mass loss phenomena affecting evolved stars, and probing the environments of black holes in active galactic nuclei. As a first breakthrough, MATISSE will enlarge the spectral domain of current optical interferometers by offering the L and M bands in addition to the N band. This will open a wide wavelength domain, ranging from 2.8 to 13 um, exploring angular scales as small as 3 mas (L band) / 10 mas (N band). As a second breakthrough, MATISSE will allow mid-infrared imaging - closure-phase aperture-synthesis imaging - with up to four Unit Telescopes (UT) or Auxiliary Telescopes (AT) of the VLTI. Moreover, MATISSE will offer a spectral resolution range from R ~ 30 to R ~ 5000. Here, we present one of the main science objectives, the study of protoplanetary disks, that has driven the instrument design and motivated several VLTI upgrades (GRA4MAT and NAOMI). We introduce the physical concept of MATISSE including a description of the signal on the detectors and an evaluation of the expected performances. We also discuss the current status of the MATISSE instrument, which is entering its testing phase, and the foreseen schedule for the next two years that will lead to the first light at Paranal.Comment: SPIE Astronomical Telescopes and Instrumentation conference, June 2016, 11 pages, 6 Figure