A slowly activating voltage-dependent K+ current in rat pituitary nerve terminals.

A novel slowly activating voltage-dependent K+ current was observed in isolated nerve terminals from rat neurohypophysis using the whole-cell configuration of the patch-clamp technique. 2. The activation kinetics of the slow current could be fitted assuming Hodgkin--Huxley-type kinetics, an exponential, n, of 1.3 and activation time constants decreasing from 4 s at -50 mV to 0.7s at +40 mV. 3. A positive shift of reversal potential was observed when [K+] was increased in the bath solution. The current is carried mainly but not exclusively by K+ ions. 4. When intracellular free [Mg2+] was low (approximately 60 microM), average current density was 74 pA pF-1 at membrane potentials around 0 mV. In 83% of nerve terminals current amplitude was > 10 pA pF-1. 5. The slow current was never observed when the pipette contained 4.6 mM free Mg2+. At a physiological level of free Mg2+ (0.5 mM) the average current density was 16 pA pF-1. 6. When nerve terminals were analysed after patch-clamp experiments for vasopressin content by immunodetection, no difference in current amplitude was found between the terminals containing vasopressin and all analysed terminals. 7. The voltage dependence of activation was fitted by a Boltzmann equation giving a half-activation potential of -37 mV and a slope factor of about 9 mV. 8. Tail current deactivation kinetics was biexponential with time constants of 0.12 and 1.5s. Kinetics was dependent on the duration of the activating pulse. 9. Noise analysis of the slow current indicated a single-channel current of 0.33 pA at +6 mV, corresponding to a single-channel conductance of 4.3 pS. 10. This is the first demonstration of a current similar to the slow K+ current, IKs, in a neurone, suggesting that a protein similar to the IKs-inducing channel protein IsK (minK) may be present in peptidergic nerve terminals. 11. The activation properties are consistent with a role of the slow current in inhibition of excitability, at least at the level of the nerve terminal

Extended polarized semiclassical model for quantum-dot cavity QED and its application to single-photon sources

We present a simple extension of the semi-classical model for a two-level system in a cavity, in order to incorporate multiple polarized transitions, such as those appearing in neutral and charged quantum dots (QDs), and two nondegenerate linearly polarized cavity modes. We verify the model by exact quantum master equation calculations, and experimentally using a neutral QD in a polarization non-degenerate micro-cavity, in both cases we observe excellent agreement. Finally, the usefulness of this approach is demonstrated by optimizing a single-photon source based on polarization postselection, where we find an increase in the brightness for optimal polarization conditions as predicted by the model.Comment: 8 pages, for simple code see https://doi.org/10.5281/zenodo.347666

Nanopore device and a method for nucleic acid analysis

A nanopore device is described wherein is provided a sample input (110), an input chamber (120), and first and second sample chambers (130, 140) connected to the input chambers (120) via first and second nanopores (135, 145)

A neighborhood search integer programming approach for wind farm layout optimization

Two models and a heuristic algorithm to address the wind farm layout optimization problem are presented. The models are linear integer programming formulations where candidate locations of wind turbines are described by binary variables. One formulation considers an approximation of the power curve by means of a stepwise constant function. The other model is based on a power-curve-free model where minimization of a measure closely related to total wind speed deficit is optimized. A special-purpose neighborhood search heuristic wraps these formulations with increasing tractability and effectiveness compared to the full model that is not contained in the heuristic. The heuristic iteratively searches for neighborhoods around the incumbent using a branch-and-cut algorithm. The number of candidate locations and neighborhood sizes are adjusted adaptively. Numerical results on a set of publicly available benchmark problems indicate that a proxy for total wind speed deficit as an objective is a functional approach, since high-quality solutions of the metric of annual energy production are obtained when using the latter function as an substitute objective. Furthermore, the proposed heuristic is able to provide good results compared to a large set of distinctive approaches that consider the turbine positions as continuous variables.</p

ER and PI3K pathway activity in primary ER positive breast cancer is associated with progression-free survival of metastatic patients under first-line tamoxifen

Estrogen receptor positive (ER+) breast cancer patients are eligible for hormonal treatment, but only around half respond. A test with higher specificity for prediction of endocrine therapy response is needed to avoid hormonal overtreatment and to enable selection of alternative treatments. A novel testing method was reported before that enables measurement of functional signal transduction pathway activity in individual cancer tissue samples, using mRNA levels of target genes of the respective pathway-specific transcription factor. Using this method, 130 primary breast cancer samples were analyzed from non-metastatic ER+ patients, treated with surgery without adjuvant hormonal therapy, who subsequently developed metastatic disease that was treated with first-line tamoxifen. Quantitative activity levels were measured of androgen and estrogen receptor (AR and ER), PI3K-FOXO, Hedgehog (HH), NFκB, TGFβ, and Wnt pathways. Based on samples with known pathway activity, thresholds were set to distinguish low from high activity. Subsequently, pathway activity levels were correlated with the tamoxifen treatment response and progression-free survival. High ER pathway activity was measured in 41% of the primary tumors and was associated with longer time to progression (PFS) of metastases during first-line tamoxifen treatment. In contrast, high PI3K, HH, and androgen receptor pathway activity was associated with shorter PFS, and high PI3K and TGFβ pathway activity with worse treatment response. Potential clinical utility of assessment of ER pathway activity lies in predicting response to hormonal therapy, while activity of PI3K, HH, TGFβ, and AR pathways may indicate failure to respond, but also opens new avenues for alternative or complementary targeted treatments

Cellular entry of nanoparticles via serum sensitive clathrin-mediated endocytosis, and plasma membrane permeabilization

Increasing production and application of nanomaterials raises significant questions regarding the potential for cellular entry and toxicity of nanoparticles. It was observed that the presence of serum reduces the cellular association of 20 nm carboxylate-modified fluorescent polystyrene beads up to 20-fold, relative to cells incubated in serum-free media. Analysis by confocal microscopy demonstrated that the presence of serum greatly reduces the cell surface association of nanoparticles, as well as the potential for internalization. However, both in the presence and absence of serum, nanoparticle entry depends upon clathrin-mediated endocytosis. Finally, experiments performed with cells cooled to 4°C suggest that a proportion of the accumulation of nanoparticles in cells was likely due to direct permeabilization of the plasma membrane