1,296 research outputs found
Self-similar shear-thickening behavior in CTAB/NaSal surfactant solutions
The effect of salt concentration Cs on the critical shear rate required for
the onset of shear thickening and apparent relaxation time of the
shear-thickened phase, has been investigated systematically for dilute
CTAB/NaSal solutions. Experimental data suggest a self-similar behavior of the
critical shear rate and relaxation time as functions of Cs. Specifically, the
former ~ Cs^(-6) whereas the latter ~ Cs^(6) such that an effective Weissenberg
number for the onset of the shear thickened phase is only weakly dependent on
Cs. A procedure has been developed to collapse the apparent shear viscosity
versus shear rate data obtained for various values of Cs into a single master
curve. The effect of Cs on the elastic modulus and mesh size of the
shear-induced gel phase for different surfactant concentrations is discussed.
Experiments performed using different flow cells (Couette and cone-and-plate)
show that the critical shear rate, relaxation time and the maximum viscosity
attained are geometry-independent. The elastic modulus of the gel phase
inferred indirectly by employing simplified hydrodynamic instability analysis
of a sheared gel-fluid interface is in qualitative agreement with that
predicted for an entangled phase of living polymers. A qualitative mechanism
that combines the effect of Cs on average micelle length and Debye parameter
with shear-induced configurational changes of rod-like micelles is proposed to
rationalize the self-similarity of SIS formation.Comment: 27 pages, 17 figure
Locomotor adaptability in persons with unilateral transtibial amputation
Background
Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective
Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods
The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results
Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions
Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb
A Variable-Density Absorption Event in NGC 3227 mapped with Suzaku and Swift
The morphology of the circumnuclear gas accreting onto supermassive black
holes in Seyfert galaxies remains a topic of much debate. As the innermost
regions of Active Galactic Nuclei (AGN) are spatially unresolved, X-ray
spectroscopy, and in particular line-of-sight absorption variability, is a key
diagnostic to map out the distribution of gas. Observations of variable X-ray
absorption in multiple Seyferts and over a wide range of timescales indicate
the presence of clumps/clouds of gas within the circumnuclear material. Eclipse
events by clumps transiting the line of sight allow us to explore the
properties of the clumps over a wide range of radial distances from the
optical/UV Broad Line Region (BLR) to beyond the dust sublimation radius.
Time-resolved absorption events have been extremely rare so far, but suggest a
range of density profiles across Seyferts. We resolve a weeks-long absorption
event in the Seyfert NGC 3227. We examine six Suzaku and twelve Swift
observations from a 2008 campaign spanning 5 weeks. We use a model accounting
for the complex spectral interplay of three differently-ionized absorbers. We
perform time-resolved spectroscopy to discern the absorption variability
behavior. We also examine the IR-to-X-ray spectral energy distribution (SED) to
test for reddening by dust. The 2008 absorption event is due to
moderately-ionized () gas covering 90% of the line of
sight. We resolve the density profile to be highly irregular, in contrast to a
previous symmetric and centrally-peaked event mapped with RXTE in the same
object. The UV data do not show significant reddening, suggesting that the
cloud is dust-free. The 2008 campaign has revealed a transit by a filamentary,
moderately-ionized cloud of variable density that is likely located in the BLR,
and possibly part of a disk wind.Comment: Accepted for publication by A&
The rise of fully turbulent flow
Over a century of research into the origin of turbulence in wallbounded shear
flows has resulted in a puzzling picture in which turbulence appears in a
variety of different states competing with laminar background flow. At slightly
higher speeds the situation changes distinctly and the entire flow is
turbulent. Neither the origin of the different states encountered during
transition, nor their front dynamics, let alone the transformation to full
turbulence could be explained to date. Combining experiments, theory and
computer simulations here we uncover the bifurcation scenario organising the
route to fully turbulent pipe flow and explain the front dynamics of the
different states encountered in the process. Key to resolving this problem is
the interpretation of the flow as a bistable system with nonlinear propagation
(advection) of turbulent fronts. These findings bridge the gap between our
understanding of the onset of turbulence and fully turbulent flows.Comment: 31 pages, 9 figure
Chemical informatics uncovers a new role for moexipril as a novel inhibitor of cAMP phosphodiesterase-4 (PDE4)
PDE4 is one of eleven known cyclic nucleotide phosphodiesterase families and plays a pivotal role in mediating hydrolytic degradation of the important cyclic nucleotide second messenger, cyclic 3′5′ adenosine monophosphate (cAMP). PDE4 inhibitors are known to have anti-inflammatory properties, but their use in the clinic has been hampered by mechanism-associated side effects that limit maximally tolerated doses. In an attempt to initiate the development of better-tolerated PDE4 inhibitors we have surveyed existing approved drugs for PDE4-inhibitory activity. With this objective, we utilised a high-throughput computational approach that identified moexipril, a well tolerated and safe angiotensin-converting enzyme (ACE) inhibitor, as a PDE4 inhibitor. Experimentally we showed that moexipril and two structurally related analogues acted in the micro molar range to inhibit PDE4 activity. Employing a FRET-based biosensor constructed from the nucleotide binding domain of the type 1 exchange protein activated by cAMP, EPAC1, we demonstrated that moexipril markedly potentiated the ability of forskolin to increase intracellular cAMP levels. Finally, we demonstrated that the PDE4 inhibitory effect of moexipril is functionally able to induce phosphorylation of the Hsp20 by cAMP dependent protein kinase A. Our data suggest that moexipril is a bona fide PDE4 inhibitor that may provide the starting point for development of novel PDE4 inhibitors with an improved therapeutic window
AU-Rich Element-Mediated mRNA Decay Can Occur Independently of the miRNA Machinery in Mouse Embryonic Fibroblasts and Drosophila S2-Cells
AU-rich elements (AREs) are regulatory sequences located in the 3′ untranslated region of many short-lived mRNAs. AREs are recognized by ARE-binding proteins and cause rapid mRNA degradation. Recent reports claimed that the function of AREs may be – at least in part – relayed through the miRNA pathway. We have revisited this hypothesis using dicer knock-out mouse embryonic fibroblasts and cultured Drosophila cells. In contrast to the published results, we find no evidence for a general requirement of the miRNA pathway in the function of AREs. Endogenous ier3 mRNA, which is known to contain a functional ARE, was degraded rapidly at indistinguishable rates in wild type and dicer knock-out mouse embryonic fibroblasts. In cultured Drosophila cells, both ARE-containing GFP reporter mRNAs and the endogenous cecA1 mRNA were resistant to depletion of the mi/siRNA factors dcr-1, dcr-2, ago1 and ago2. Furthermore, the Drosophila miRNA originally proposed to recognize AU-rich elements, miR-289, is not detectably expressed in flies or cultured S2 cells. Even our attempts to overexpress this miRNA from its genomic hairpin sequence failed. Thus, this sequence cannot serve as link between the miRNA and the AU-rich element mediated silencing pathways. Taken together, our studies in mammalian and Drosophila cells strongly argue that AREs can function independently of miRNAs
Histopathologic findings in malignant peripheral nerve sheath tumor predict response to radiotherapy and overall survival
BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is an aggressive and poorly understood malignant neoplasm. Even in the setting of multimodal therapy, the clinical course of MPNST is frequently marked by metastatic conversion and poor overall prognosis, with optimal treatment paradigms for this rare tumor unknown.
METHODS: We reviewed the medical records and histopathology of 54 consecutive patients who were treated at University of California San Francisco between 1990 and 2018.
RESULTS: Our cohort consisted of 24 male and 30 female patients (median age 38 years). Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) sarcoma grading criteria segregated patients into groups with differences in overall survival (OS) (
CONCLUSIONS: Our results lend support to the FNCLCC sarcoma grading criteria as a prognostic scheme for MPNST, although few cases of grade 1 were included. Further, we identify increased Ki-67 labeling as a strong predictor of poor OS from MPNST. Finally, we identify a subset of MPNSTs with a predictive immunohistochemical profile that has improved local control with adjuvant radiotherapy. These data provide insights into the grading and therapy for patients with MPNST, although further studies are needed for independent validation
PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells
Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al
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