530 research outputs found
Phenotypic Plasticity in Juvenile Jellyfish Medusae Facilitates Effective Animal–Fluid Interaction
Locomotion and feeding in marine animals are intimately linked to the flow dynamics created by specialized body parts. This interaction is of particular importance during ontogeny, when changes in behaviour and scale challenge the organism with shifts in fluid regimes and altered functionality. Previous studies have indicated that Scyphozoan jellyfish ontogeny accommodates the changes in fluid dynamics associated with increasing body dimensions and velocities during development. However, in addition to scale and behaviour that—to a certain degree—underlie the control of the animal, flow dynamics are also dependent on external factors such as temperature. Here, we show phenotypic plasticity in juvenile Aurelia aurita medusae, where morphogenesis is adapted to altered fluid regimes imposed by changes in ambient temperature. In particular, differential proportional growth was found to compensate for temperature-dependent changes in viscous effects, enabling the animal to use adhering water boundary layers as ‘paddles’—and thus economize tissue—at low temperatures, while switching to tissue-dominated propulsion at higher temperatures where the boundary layer thickness is insufficient to serve for paddling. This effect was predicted by a model of animal–fluid interaction and confirmed empirically by flow-field visualization and assays of propulsion efficiency
Patient evaluation of the use of follitropin alfa in a prefilled ready-to-use injection pen in assisted reproductive technology: an observational study
<p>Abstract</p> <p>Background</p> <p>Self-administration of recombinant human follicle-stimulating hormone (r-hFSH) can be performed using injection pen devices by women undergoing assisted reproductive technology procedures. The objective of this study was to explore the use of the prefilled follitropin alfa pen in routine assisted reproductive technology procedures in Germany.</p> <p>Methods</p> <p>This prospective, observational study was conducted across 43 German IVF centres over a period of 1.75 years. Patients who had used the prefilled follitropin alfa pen in the current or a previous cycle of controlled ovarian stimulation completed a questionnaire to assess their opinions of the device.</p> <p>Results</p> <p>A total of 5328 patients were included in the study. Of these, 2888 reported that they had previous experience of daily FSH injections. Significantly more patients reported that less training was required to use the prefilled follitropin alfa pen than a syringe and lyophilized powder (1997/3081 [64.8%]; p < 0.001 'less' versus 'more' training). Significantly more patients rated the prefilled follitropin alfa pen as easier in terms of use (2321/3206, 72.4%; p < 0.001 'much more easy' versus 'less easy') and daily injection (2384/3262, 73.1%; p < 0.001 'much more easy' versus 'less easy') than existing injection methods. Approximately one third of respondents rated the prefilled follitropin alfa pen as easier to use than the follitropin beta pen with reloadable cartridges. The majority (3378/4024, 83.9%) of patients had a general preference for the prefilled follitropin alfa pen over other injection methods.</p> <p>Conclusions</p> <p>In this questionnaire-based survey, routine use of the prefilled follitropin alfa pen was well accepted and associated with favourable patient perceptions. Users of the pen found it easier to initially learn how to use, and subsequently use, than other injection methods. In general, the prefilled follitropin alfa pen was the preferred method for self-administration of gonadotrophins. Together with previous findings, the results here indicate a high level of patient satisfaction among users of the prefilled follitropin alfa pen for daily self-administration of r-hFSH.</p
Improved estimation of Fokker-Planck equations through optimisation
An improved method for the description of hierarchical complex systems by
means of a Fokker-Planck equation is presented. In particular the
limited-memory Broyden-Fletcher-Goldfarb-Shanno algorithm for constraint
problems (L-BFGS-B) is used to minimize the distance between the numerical
solutions of the Fokker-Planck equation and the empirical probability density
functions and thus to estimate properly the drift and diffusion term of the
Fokker-Planck equation. The optimisation routine is applied to a time series of
velocity measurements obtained from a turbulent helium gas jet in order to
demonstrate the benefits and to quantify the improvements of this new
optimisation routine
Multiscale reconstruction of time series
A new method is proposed which allows a reconstruction of time series based
on higher order multiscale statistics given by a hierarchical process. This
method is able to model the time series not only on a specific scale but for a
range of scales. It is possible to generate complete new time series, or to
model the next steps for a given sequence of data. The method itself is based
on the joint probability density which can be extracted directly from given
data, thus no estimation of parameters is necessary. The results of this
approach are shown for a real world dataset, namely for turbulence. The
unconditional and conditional probability densities of the original and
reconstructed time series are compared and the ability to reproduce both is
demonstrated. Therefore in the case of Markov properties the method proposed
here is able to generate artificial time series with correct n-point
statistics.Comment: 4 pages, 3 figure
Metallo supramolecular cylinders inhibit HIV-1 TAR-TAT complex formation and viral replication in cellulo
Shape-selective recognition of nucleic acid structures by supramolecular drugs offers the potential to treat disease. The Trans Activation Response (TAR) region is a region of high secondary structure within the human immunodeficiency virus-1 (HIV-1) RNA that complexes with the virus-encoded Transactivator protein (TAT) and regulates viral transcription. Herein, we explore different metallo-supramolecular triple stranded helicates (cylinders) that target the TAR bulge motif and inhibit the formation of TAR-TAT complexes and HIV infection. Cylinders that incorporate Ni(II) and Ru(II) showed the most potent anti-viral activity with limited evidence of cellular cytotoxicity. These metallo-supramolecular compounds provide an exciting avenue for developing a new class of anti-viral agents
An Iterative Procedure for the Estimation of Drift and Diffusion Coefficients of Langevin Processes
A general method is proposed which allows one to estimate drift and diffusion
coefficients of a stochastic process governed by a Langevin equation. It
extends a previously devised approach [R. Friedrich et al., Physics Letters A
271, 217 (2000)], which requires sufficiently high sampling rates. The analysis
is based on an iterative procedure minimizing the Kullback-Leibler distance
between measured and estimated two time joint probability distributions of the
process.Comment: 4 pages, 5 figure
Jellyfish inspired soft robot prototype which uses circumferential contraction for jet propulsion
© Springer International Publishing AG 2017. Several robotic jellyfish have been designed over the years, yet none have properly mimicked the very efficient method of propulsion that jellyfish use. Using circumferential contraction, water is pushed out the bottom of the bell creating upwards thrust. Jellyfish use this basic movement along with more complex features to move around the seas. In this paper, we attempt to mimic this circumferential contraction using hydraulically actuated silicone bellows that expand and contract a bell made of flexible silicone skin. 3D printed polylactic acid (PLA) was used to make the structure of the robot, and hinges and jubilee clips were used to fasten it together in order to maintain exchangeability of parts. The jellyfish expands and contracts using a pump with a simple on-off control which switches dependent on the internal pressure of the hydraulic system. This very simple control mechanism is similar to real jellyfish, and much like jellyfish, our design attempts to use both passive and active movements to maximize thrust
S6K1 and 4E-BP1 Are Independent Regulated and Control Cellular Growth in Bladder Cancer
Aberrant activation and mutation status of proteins in the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and the mitogen activated protein kinase (MAPK) signaling pathways have been linked to tumorigenesis in various tumors including urothelial carcinoma (UC). However, anti-tumor therapy with small molecule inhibitors against mTOR turned out to be less successful than expected. We characterized the molecular mechanism of this pathway in urothelial carcinoma by interfering with different molecular components using small chemical inhibitors and siRNA technology and analyzed effects on the molecular activation status, cell growth, proliferation and apoptosis. In a majority of tested cell lines constitutive activation of the PI3K was observed. Manipulation of mTOR or Akt expression or activity only regulated phosphorylation of S6K1 but not 4E-BP1. Instead, we provide evidence for an alternative mTOR independent but PI3K dependent regulation of 4E-BP1. Only the simultaneous inhibition of both S6K1 and 4E-BP1 suppressed cell growth efficiently. Crosstalk between PI3K and the MAPK signaling pathway is mediated via PI3K and indirect by S6K1 activity. Inhibition of MEK1/2 results in activation of Akt but not mTOR/S6K1 or 4E-BP1. Our data suggest that 4E-BP1 is a potential new target molecule and stratification marker for anti cancer therapy in UC and support the consideration of a multi-targeting approach against PI3K, mTORC1/2 and MAPK
DAMP Signaling is a Key Pathway Inducing Immune Modulation after Brain Injury
Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We investigated the inflammatory potency of HMGB1 and its signaling pathways by immunological in vivo and in vitro techniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, was studied in various transgenic animal models and by pharmacological blockade. Our results indicate that HMGB1 was released from the ischemic brain in the hyperacute phase of stroke in mice and patients. Cytokines secreted in the periphery in response to brain injury induced sickness behavior, which could be abrogated by inhibition of the HMGB1-RAGE pathway or direct cytokine neutralization. Subsequently, HMGB1-release induced bone marrow egress and splenic proliferation of bone marrow-derived suppressor cells, inhibiting the adaptive immune responses in vivo and vitro. Furthermore, HMGB1-RAGE signaling resulted in functional exhaustion of mature monocytes and lymphopenia, the hallmarks of immune suppression after extensive ischemia. This study introduces the HMGB1-RAGE-mediated pathway as a key mechanism explaining the complex postischemic brain-immune interactions
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