Dopamine D-3 receptors regulate GABA(A) receptor function through a phospho-dependent endocytosis mechanism in nucleus accumbens

The dopamine D-3 receptor, which is highly enriched in nucleus accumbens (NAc), has been suggested to play an important role in reinforcement and reward. To understand the potential cellular mechanism underlying D-3 receptor functions, we examined the effect of D-3 receptor activation on GABA(A) receptor (GABA(A)R)-mediated current and inhibitory synaptic transmission in medium spiny neurons of NAc. Application of PD128907 [(4aR, 10bR)-3,4a, 4,10b-tetrahydro-4-propyl-2H, 5H-[1] benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride], a specific D-3 receptor agonist, caused a significant reduction of GABAAR current in acutely dissociated NAc neurons and miniature IPSC amplitude in NAc slices. This effect was blocked by dialysis with a dynamin inhibitory peptide, which prevents the clathrin/activator protein 2 (AP2)-mediated GABA(A) receptor endocytosis. In addition, the D-3 effect on GABA(A)R current was prevented by agents that manipulate protein kinase A (PKA) activity. Infusion of a peptide derived from GABA(A) beta subunits, which contains an atypical binding motif for the clathrin AP2 adaptor complex and the major PKA phosphorylation sites and binds with high affinity to AP2 only when dephosphorylated, diminished the D-3 regulation of IPSC amplitude. The phosphorylated equivalent of the peptide was without effect. Moreover, PD128907 increased GABAAR internalization and reduced the surface expression of GABA(A) receptor beta subunits in NAc slices, which was prevented by dynamin inhibitory peptide or cAMP treatment. Together, our results suggest that D-3 receptor activation suppresses the efficacy of inhibitory synaptic transmission in NAc by increasing the phospho-dependent endocytosis of GABA(A) receptors

Anode-Coupled Readout for Light Collection in Liquid Argon TPCs

This paper will discuss a new method of signal read-out from photon detectors in ultra-large, underground liquid argon time projection chambers. In this design, the signal from the light collection system is coupled via capacitive plates to the TPC wire-planes. This signal is then read out using the same cabling and electronics as the charge information. This greatly benefits light collection: it eliminates the need for an independent readout, substantially reducing cost; It reduces the number of cables in the vapor region of the TPC that can produce impurities; And it cuts down on the number of feed-throughs in the cryostat wall that can cause heat-leaks and potential points of failure. We present experimental results that demonstrate the sensitivity of a LArTPC wire plane to photon detector signals. We also simulate the effect of a 1 $\mu$s shaping time and a 2 MHz sampling rate on these signals in the presence of noise, and find that a single photoelectron timing resolution of $\sim$30 ns can be achieved.Comment: 16 pages, 15 figure

Simulations of a mortality plateau in the sexual Penna model for biological ageing

The Penna model is a strategy to simulate the genetic dynamics of age-structured populations, in which the individuals genomes are represented by bit-strings. It provides a simple metaphor for the evolutionary process in terms of the mutation accumulation theory. In its original version, an individual dies due to inherited diseases when its current number of accumulated mutations, n, reaches a threshold value, T. Since the number of accumulated diseases increases with age, the probability to die is zero for very young ages (n = T). Here, instead of using a step function to determine the genetic death age, we test several other functions that may or may not slightly increase the death probability at young ages (n < T), but that decreases this probability at old ones. Our purpose is to study the oldest old effect, that is, a plateau in the mortality curves at advanced ages. Imposing certain conditions, it has been possible to obtain a clear plateau using the Penna model. However, a more realistic one appears when a modified version, that keeps the population size fixed without fluctuations, is used. We also find a relation between the birth rate, the age-structure of the population and the death probability.Comment: submitted to Phys. Rev.

End of Life: A Family Narrative

This paper is based on ethnographic research that examines family reaction to an elderly husband and father's end of life. From a group of 30 families in our study (family defined as a widow aged 70 and over and two adult biological children between the ages of 40 and 60), we offer an extreme case example of family bereavement. We report our findings through the open-ended responses of a widow and two children who were interviewed ten months after the death of the husband and father. Three general themes emerged: (1) how the family imputes meaning to the end of life, (2) changes in the roles of family members, and (3) the family's ways of coping with the death, particularly through their belief system. A key finding is that the meaning family members find in their loved one's death is tied to the context of his death (how and where he died), their perception of his quality of life as a whole, and their philosophical, religious, and spiritual beliefs about life, death, and the afterlife that are already in place

Improved TPB-coated Light Guides for Liquid Argon TPC Light Detection Systems

Scintillation light produced in liquid argon (LAr) must be shifted from 128 nm to visible wavelengths in light detection systems used for liquid argon time-projection chambers (LArTPCs). To date, LArTPC light collection systems have employed tetraphenyl butadiene (TPB) coatings on photomultiplier tubes (PMTs) or plates placed in front of the PMTs. Recently, a new approach using TPB-coated light guides was proposed. In this paper, we report on light guides with improved attenuation lengths above 100 cm when measured in air. This is an important step in the development of meter-scale light guides for future LArTPCs. Improvements come from using a new acrylic-based coating, diamond-polished cast UV transmitting acrylic bars, and a hand-dipping technique to coat the bars. We discuss a model for connecting bar response in air to response in liquid argon and compare this to data taken in liquid argon. The good agreement between the prediction of the model and the measured response in liquid argon demonstrates that characterization in air is sufficient for quality control of bar production. This model can be used in simulations of light guides for future experiments.Comment: 25 pages, 20 figure

Border Detection on Digitized Skin Tumor Images

A radial search technique is presented for detecting skin tumor borders in clinical dermatology images. First, it includes two rounds of radial search based on the same tumor center. The first-round search is independent, and the second-round search is knowledge-based tracking. Then a rescan with a new center is used to solve the blind-spot problem. The algorithm is tested on model images with excellent performance, and on 300 real clinical images with a satisfactory resul

Covering problems in edge- and node-weighted graphs

This paper discusses the graph covering problem in which a set of edges in an edge- and node-weighted graph is chosen to satisfy some covering constraints while minimizing the sum of the weights. In this problem, because of the large integrality gap of a natural linear programming (LP) relaxation, LP rounding algorithms based on the relaxation yield poor performance. Here we propose a stronger LP relaxation for the graph covering problem. The proposed relaxation is applied to designing primal-dual algorithms for two fundamental graph covering problems: the prize-collecting edge dominating set problem and the multicut problem in trees. Our algorithms are an exact polynomial-time algorithm for the former problem, and a 2-approximation algorithm for the latter problem, respectively. These results match the currently known best results for purely edge-weighted graphs.Comment: To appear in SWAT 201

Fermi-surface induced modulation in an optimally doped YBCO superconductor

We have observed a Fermi-surface (FS) induced lattice modulation in a YBCO superconductor with a wavevector along CuO chains, {\it i.e.} ${\bf q}_1$=(0,$\delta$,0). The value of $\delta\sim0.21$ is twice the Fermi wavevector ($2{\bf k}_F$) along {\bf b*} connecting nearly nested FS `ridges'. The ${\bf q}_1$ modulation exists only within O-vacancy-ordered islands (characterized by ${\bf q}_0$=$(\frac14,0,0))$ and persists well above and below $T_c$. Our results are consistent with the presence of a FS-induced charge-density wave

The photomultiplier tube calibration system of the MicroBooNE experiment

We report on the design and construction of a LED-based fiber calibration system for large liquid argon time projection detectors. This system was developed to calibrate the optical systems of the MicroBooNE experiment. As well as detailing the materials and installation procedure, we provide technical drawings and specifications so that the system may be easily replicated in future LArTPC detectors.National Science Foundation (U.S.) (Grant PHY-1205175