Mechanical measurements of heterogeneity and length scale effects in PEG-based hydrogels.

Colloidal-probe spherical indentation load-relaxation experiments with a probe radius of 3 μm are conducted on poly(ethylene glycol) (PEG) hydrogel materials to quantify their steady-state mechanical properties and time-dependent transport properties via a single experiment. PEG-based hydrogels are shown to be heterogeneous in both morphology and mechanical stiffness at this scale; a linear-harmonic interpolation of hyperelastic Mooney-Rivlin and Boussinesq flat-punch indentation models was used to describe the steady-state response of the hydrogels and determine upper and lower bounds for indentation moduli. Analysis of the transient load-relaxation response during displacement-controlled hold periods provides a means of extracting two time constants τ1 and τ2, where τ1 and τ2 are assigned to the viscoelastic and poroelastic properties, respectively. Large τ2 values at small indentation depths provide evidence of a non-equilibrium state characterized by a phenomenon that restricts poroelastic fluid flow through the material; for larger indentations, the variability in τ2 values decreases and pore sizes estimated from τ2via indentation approach those measured via macroscopic swelling experiments. The contact probe methodology developed here provides a means of assessing hydrogel heterogeneity, including time-dependent mechanical and transport properties, and has potential implications in hydrogel biomedical and engineering applications.The authors would like to acknowledge funding from the National Institutes of Health.This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5SM01210

Tidally induced lateral dispersion of the Storfjorden overflow plume

We investigate the flow of brine-enriched shelf water from Storfjorden (Svalbard) into Fram Strait and onto the western Svalbard Shelf using a regional set-up of NEMO-SHELF, a 3-D numerical ocean circulation model. The model is set up with realistic bathymetry, atmospheric forcing, open boundary conditions and tides. The model has 3 km horizontal resolution and 50 vertical levels in the sh-coordinate system which is specially designed to resolve bottom boundary layer processes. In a series of modelling experiments we focus on the influence of tides on the propagation of the dense water plume by comparing results from tidal and non-tidal model runs. Comparisons of non-tidal to tidal simulations reveal a hotspot of tidally induced horizontal diffusion leading to the lateral dispersion of the plume at the southernmost headland of Spitsbergen which is in close proximity to the plume path. As a result the lighter fractions in the diluted upper layer of the plume are drawn into the shallow coastal current that carries Storfjorden water onto the western Svalbard Shelf, while the dense bottom layer continues to sink down the slope. This bifurcation of the plume into a diluted shelf branch and a dense downslope branch is enhanced by tidally induced shear dispersion at the headland. Tidal effects at the headland are shown to cause a net reduction in the downslope flux of Storfjorden water into the deep Fram Strait. This finding contrasts previous results from observations of a dense plume on a different shelf without abrupt topography

Future aspects of renal transplantation

New and exciting advances in renal transplantation are continuously being made, and the horizons for organ transplantation are bright and open. This article reviews only a few of the newer advances that will allow renal transplantation to become even more widespread and successful. The important and exciting implications for extrarenal organ transplantation are immediately evident. © 1988 Springer-Verlag

Geometric Mixing, Peristalsis, and the Geometric Phase of the Stomach

Mixing fluid in a container at low Reynolds number - in an inertialess environment - is not a trivial task. Reciprocating motions merely lead to cycles of mixing and unmixing, so continuous rotation, as used in many technological applications, would appear to be necessary. However, there is another solution: movement of the walls in a cyclical fashion to introduce a geometric phase. We show using journal-bearing flow as a model that such geometric mixing is a general tool for using deformable boundaries that return to the same position to mix fluid at low Reynolds number. We then simulate a biological example: we show that mixing in the stomach functions because of the "belly phase": peristaltic movement of the walls in a cyclical fashion introduces a geometric phase that avoids unmixing.Comment: Revised, published versio

Neutrino-driven Explosions

The question why and how core-collapse supernovae (SNe) explode is one of the central and most long-standing riddles of stellar astrophysics. A solution is crucial for deciphering the SN phenomenon, for predicting observable signals such as light curves and spectra, nucleosynthesis, neutrinos, and gravitational waves, for defining the role of SNe in the evolution of galaxies, and for explaining the birth conditions and properties of neutron stars (NSs) and stellar-mass black holes. Since the formation of such compact remnants releases over hundred times more energy in neutrinos than the SN in the explosion, neutrinos can be the decisive agents for powering the SN outburst. According to the standard paradigm of the neutrino-driven mechanism, the energy transfer by the intense neutrino flux to the medium behind the stagnating core-bounce shock, assisted by violent hydrodynamic mass motions (sometimes subsumed by the term "turbulence"), revives the outward shock motion and thus initiates the SN blast. Because of the weak coupling of neutrinos in the region of this energy deposition, detailed, multidimensional hydrodynamic models including neutrino transport and a wide variety of physics are needed to assess the viability of the mechanism. Owing to advanced numerical codes and increasing supercomputer power, considerable progress has been achieved in our understanding of the physical processes that have to act in concert for the success of neutrino-driven explosions. First studies begin to reveal observational implications and avenues to test the theoretical picture by data from individual SNe and SN remnants but also from population-integrated observables. While models will be further refined, a real breakthrough is expected through the next Galactic core-collapse SN, when neutrinos and gravitational waves can be used to probe the conditions deep inside the dying star. (abridged)Comment: Author version of chapter for 'Handbook of Supernovae,' edited by A. Alsabti and P. Murdin, Springer. 54 pages, 13 figure

Degenerate Stars and Gravitational Collapse in AdS/CFT

We construct composite CFT operators from a large number of fermionic primary fields corresponding to states that are holographically dual to a zero temperature Fermi gas in AdS space. We identify a large N regime in which the fermions behave as free particles. In the hydrodynamic limit the Fermi gas forms a degenerate star with a radius determined by the Fermi level, and a mass and angular momentum that exactly matches the boundary calculations. Next we consider an interacting regime, and calculate the effect of the gravitational back-reaction on the radius and the mass of the star using the Tolman-Oppenheimer-Volkoff equations. Ignoring other interactions, we determine the "Chandrasekhar limit" beyond which the degenerate star (presumably) undergoes gravitational collapse towards a black hole. This is interpreted on the boundary as a high density phase transition from a cold baryonic phase to a hot deconfined phase.Comment: 75 page

Cytosine-to-Uracil Deamination by SssI DNA Methyltransferase

The prokaryotic DNA(cytosine-5)methyltransferase M.SssI shares the specificity of eukaryotic DNA methyltransferases (CG) and is an important model and experimental tool in the study of eukaryotic DNA methylation. Previously, M.SssI was shown to be able to catalyze deamination of the target cytosine to uracil if the methyl donor S-adenosyl-methionine (SAM) was missing from the reaction. To test whether this side-activity of the enzyme can be used to distinguish between unmethylated and C5-methylated cytosines in CG dinucleotides, we re-investigated, using a sensitive genetic reversion assay, the cytosine deaminase activity of M.SssI. Confirming previous results we showed that M.SssI can deaminate cytosine to uracil in a slow reaction in the absence of SAM and that the rate of this reaction can be increased by the SAM analogue 5’-amino-5’-deoxyadenosine. We could not detect M.SssI-catalyzed deamination of C5-methylcytosine (m5C). We found conditions where the rate of M.SssI mediated C-to-U deamination was at least 100-fold higher than the rate of m5C-to-T conversion. Although this difference in reactivities suggests that the enzyme could be used to identify C5-methylated cytosines in the epigenetically important CG dinucleotides, the rate of M.SssI mediated cytosine deamination is too low to become an enzymatic alternative to the bisulfite reaction. Amino acid replacements in the presumed SAM binding pocket of M.SssI (F17S and G19D) resulted in greatly reduced methyltransferase activity. The G19D variant showed cytosine deaminase activity in E. coli, at physiological SAM concentrations. Interestingly, the C-to-U deaminase activity was also detectable in an E. coli ung+ host proficient in uracil excision repair

Inhibition of Y1 receptor signaling improves islet transplant outcome

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.info:eu-repo/semantics/publishe

A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

Effects of a brief mindfulness-based intervention on emotional regulation and levels of mindfulness in senior students

Mindfulness-based interventions have been applied in diverse populations and achieved mental health benefits. This study examined the effects of a brief mindfulness program for emotional regulation and levels of mindfulness on senior students in Brazil. The intervention consisted of six weekly meetings attended by 30 participants. It is a pre-experimental research, with pre- and post-test comparative and correlation measurements. The preliminary results, which relied on parametrical and non-parametrical tests, revealed a reduction in total emotional regulation difficulties (p = 0.0001; r = − 0.55). Also, there was an increase in the levels of mindfulness in the subtests for both dimensions under evaluation: “Awareness” (p = 0.0001; d = 0.77) and “Acceptance” (p = 0.048; d = 0.37). By associating the amount of meditative practices performed by students with the variables, a significant positive correlation was found with the mindfulness dimension “Awareness” (rP = 0.422; p = 0.020), and there was a significant negative correlation with Difficulties in emotion regulation (rS = − 0.478; p = 0.008) and with its respective subscales “Non-acceptance” (rS = − 0.654; p = 0.0001) and “Clarity” (rS = − 0.463; p = 0.010). In conclusion, the application of a brief mindfulness-based intervention is promising in Brazilian university contexts; moreover, it can bring benefits to students, e.g., an increase in emotion regulation as well as in levels of mindfulness. We suggest that further research should use an experimental design and follow-up.info:eu-repo/semantics/publishedVersio