Evaluation of different drug classes on transient sciatic nerve injury-depressed marble burying in mice

A great need exists for the identification of new effective analgesics to treat sustained pain. However, most preclinical nociceptive assays measure behavioral responses evoked by noxious stimuli (i.e., pain-stimulated behavior), which presents a challenge to distinguish between motor impairing and antinociceptive effects of drugs. Here, we demonstrate that chronic constriction injury of the sciatic nerve (CCI) elicits common pain-stimulated responses (i.e., mechanical allodynia and thermal hyperalgesia) as well as reduces marble burying/digging behaviors that occur during the early stages of the neuropathy and resolve within one week. Whereas drugs representing distinct classes of analgesics (i.e., morphine, valdecoxib, and gabapentin) reversed both CCI-induced and CCI-depressed nociceptive measures, diazepam lacked antinociceptive effects in all assays and the kappa opioid receptor agonist U69593 reversed pain-stimulated, but not pain-depressed behaviors. In addition, we tested drugs targeting distinct components of the endocannabinoid system, including agonists at cannabinoid receptors type 1 (CB1) and type 2 (CB2), as well as inhibitors of the endocannabinoid regulating enzymes fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL). Each of these drugs reversed all CCI-induced nociceptive measures, with the exception of the FAAH inhibitor that reversed pain-stimulated behaviors, only. These findings support the use of the mouse marble-burying assay as a model of pain-depressed behavior within the first week of sciatic nerve injury to examine candidate analgesics. These data also support existing preclinical research that cannabinoid receptor agonists and inhibitors of endocannabinoid regulating enzymes merit consideration for the treatment of pain.Molecular Physiolog

Dead layer on silicon p–i–n diode charged-particle detectors

Semiconductor detectors in general have a dead layer at their surfaces that is either a result of natural or induced passivation, or is formed during the process of making a contact. Charged particles passing through this region produce ionization that is incompletely collected and recorded, which leads to departures from the ideal in both energy deposition and resolution. The silicon p-i-n diode used in the KATRIN neutrinomass experiment has such a dead layer. We have constructed a detailed Monte Carlo model for the passage of electrons from vacuum into a silicon detector, and compared the measured energy spectra to the predicted ones for a range of energies from 12 to 20 keV. The comparison provides experimental evidence that a substantial fraction of the ionization produced in the "dead" layer evidently escapes by diffusion, with 46% being collected in the depletion zone and the balance being neutralized at the contact or by bulk recombination. The most elementary model of a thinner dead layer from which no charge is collected is strongly disfavored

The design, construction, and commissioning of the KATRIN experiment

The KArlsruhe TRItium Neutrino (KATRIN) experiment, which aims to make a direct and model-independent determination of the absolute neutrino mass scale, is a complex experiment with many components. More than 15 years ago, we published a technical design report (TDR) [1] to describe the hardware design and requirements to achieve our sensitivity goal of 0.2 eV at 90% C.L. on the neutrino mass. Since then there has been considerable progress, culminating in the publication of first neutrino mass results with the entire beamline operating [2]. In this paper, we document the current state of all completed beamline components (as of the first neutrino mass measurement campaign), demonstrate our ability to reliably and stably control them over long times, and present details on their respective commissioning campaigns

Focal-plane detector system for the KATRIN experiment

The focal-plane detector system for the KArlsruhe TRItium Neutrino (KATRIN) experiment consists of a multi-pixel silicon p-i-n-diode array, custom readout electronics, two superconducting solenoid magnets, an ultra high-vacuum system, a high-vacuum system, calibration and monitoring devices, a scintillating veto, and a custom data-acquisition system. It is designed to detect the low-energy electrons selected by the KATRIN main spectrometer. We describe the system and summarize its performance after its final installation.Comment: 28 pages. Two figures revised for clarity. Final version published in Nucl. Inst. Meth.

Measurement of the νe and total 8B solar neutrino fluxes with the Sudbury Neutrino Observatory phase-III data set

This paper details the solar neutrino analysis of the 385.17-day phase-III data set acquired by the Sudbury Neutrino Observatory (SNO). An array of 3He proportional counters was installed in the heavy-water target to measure precisely the rate of neutrino-deuteron neutral-current interactions. This technique to determine the total active 8B solar neutrino flux was largely independent of the methods employed in previous phases. The total flux of active neutrinos was measured to be 5.54-0.31+0.33(stat.)-0.34+0.36(syst.)×106 cm-2 s-1, consistent with previous measurements and standard solar models. A global analysis of solar and reactor neutrino mixing parameters yielded the best-fit values of Δm2=7.59-0.21+0.19×10 -5eV2 and θ=34.4-1.2+1.3degrees

White Oak Creek embayment sediment retention structure design and construction

White Oak Creek is the major surface water drainage throughout the Department of Energy (DOE) Oak Ridge National Laboratory (ORNL). Samples taken from the lower portion of the creek revealed high levels of Cesium 137 and lower level of Cobalt 60 in near surface sediment. Other contaminants present in the sediment included: lead, mercury, chromium, and PCBs. In October 1990, DOE, US Environmental Protection Agency (EPA), and Tennessee Department of Environment and Conservation (TDEC) agreed to initiate a time critical removal action in accordance with the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) to prevent the transport of the contaminated sediments into the Clinch River system. This paper discusses the environmental, regulatory, design, and construction issues that were encountered in conducting the remediation work

The structure of the upper atmosphere of Mars: In situ accelerometer measurements from Mars Global Surveyor

The Mars Global Surveyor (MGS) z-axis accelerometer has obtained over 200 vertical structures of thermospheric density, temperature, and pressure, ranging from 110 to 170 kilometers, compared to only three previous such vertical structures. In November 1997, a regional dust storm in the Southern Hemisphere triggered an unexpectedly large thermospheric response at mid- northern latitudes, increasing the altitude of thermospheric pressure surfaces there by as much as 8 kilometers and indicating a strong global thermospheric response to a regional dust storm. Throughout the MGS mission, thermospheric density bulges have been detected on opposite sides of the planet near 90°E and 90°W, in the vicinity of maximum terrain heights. This wave 2 pattern may be caused by topographically-forced planetary waves propagating up from the lower atmosphere