Migration of noble gas tracers at the site of an underground nuclear explosion at the Nevada National Security Site.

As part of an underground gas migration study, two radioactive noble gases (37Ar and 127Xe) and two stable tracer gases (SF6 and PFDMCH) were injected into a historic nuclear explosion test chimney and allowed to migrate naturally. The purpose of this experiment was to provide a bounding case (natural transport) for the flow of radioactive noble gases following an underground nuclear explosion. To accomplish this, soil gas samples were collected from a series of boreholes and a range of depths from the shallow subsurface (3 m) to deeper levels (~160 m) over a period of eleven months. These samples have provided insights into the development and evolution of the subsurface plume and constrained the relative migration rates of the radioactive and stable gas species in the case when the driving pressure from the cavity is low. Analysis of the samples concluded that the stable tracer SF6 was consistently enriched in the subsurface samples relative to the radiotracer 127Xe, but the ratios of SF6 and 37Ar remained similar throughout the samples.

Measurements of Argon-39 at the U20az underground nuclear explosion site.

Pacific Northwest National Laboratory reports on the detection of 39Ar at the location of an underground nuclear explosion on the Nevada Nuclear Security Site. The presence of 39Ar was not anticipated at the outset of the experimental campaign but results from this work demonstrated that it is present, along with 37Ar and 85Kr in the subsurface at the site of an underground nuclear explosion. Our analysis showed that by using state-of-the-art technology optimized for radioargon measurements, it was difficult to distinguish 39Ar from the fission product 85Kr. Proportional counters are currently used for high-sensitivity measurement of 37Ar and 39Ar. Physical and chemical separation processes are used to separate argon from air or soil gas, yielding pure argon with contaminant gases reduced to the parts-per-million level or below. However, even with purification at these levels, the beta decay signature of 85Kr can be mistaken for that of 39Ar, and the presence of either isotope increases the measurement background level for the measurement of 37Ar. Measured values for the 39Ar measured at the site ranged from 36,000 milli- Becquerel/standard-cubic-meter-of-air (mBq/SCM) for shallow bore holes to 997,000 mBq/SCM from the rubble chimney from the underground nuclear explosion.

Development of a low-level 39Ar calibration standard - Analysis by absolute gas counting measurements augmented with simulation.

This paper describes the generation of 39Ar, via reactor irradiation of potassium carbonate, followed by quantitative analysis (length-compensated proportional counting) to yield two calibration standards that are respectively 50 and 3 times atmospheric background levels. Measurements were performed in Pacific Northwest National Laboratory's shallow underground counting laboratory studying the effect of gas density on beta-transport; these results are compared with simulation. The total expanded uncertainty of the specific activity for the ~50× 39Ar in P10 standard is 3.6% (k=2).

First results of a simultaneous measurement of tritium and (14)C in an ultra-low-background proportional counter for environmental sources of methane.

Simultaneous measurement of tritium and (14)C would provide an added tool for tracing organic compounds through environmental systems and is possible via beta energy spectroscopy of sample-derived methane in internal-source gas proportional counters. Since the mid-1960's atmospheric tritium and (14)C have fallen dramatically as the isotopic injections from aboveground nuclear testing have been diluted into the ocean and biosphere. In this work, the feasibility of simultaneous tritium and (14)C measurements via proportional counters is revisited in light of significant changes in both the atmospheric and biosphere isotopics and the development of new ultra-low-background gas proportional counting capabilities for small samples (roughly 50 cc methane). A Geant4 Monte Carlo model of a Pacific Northwest National Laboratory (PNNL) proportional counter response to tritium and (14)C is used to analyze small samples of two different methane sources to illustrate the range of applicability of contemporary simultaneous measurements and their limitations. Because the two methane sources examined were not sample size limited, we could compare the small-sample measurements performed at PNNL with analysis of larger samples performed at a commercial laboratory. These first results show that the dual-isotope simultaneous measurement is well matched for methane samples that are atmospheric or have an elevated source of tritium (i.e. landfill gas). However, for samples with low/modern tritium isotopics (rainwater), commercial separation and counting is a better fit.

Development of a low-level (37)Ar calibration standard.

Argon-37 is an environmental signature of an underground nuclear explosion. Producing and quantifying low-level (37)Ar standards is an important step in the development of sensitive field measurement instruments. This paper describes progress at Pacific Northwest National Laboratory in developing a process to generate and quantify low-level (37)Ar standards, which can be used to calibrate sensitive field systems at activities consistent with soil background levels. This paper presents a discussion of the measurement analysis, along with assumptions and uncertainty estimates.

Randomized clinical trial investigating the stress response from two different methods of analgesia after laparoscopic colorectal surgery.

BACKGROUND: One of the key elements of managed recovery is thought to be suppression of the neuroendocrine response using regional analgesics. This may be superfluous in laparoscopic colorectal surgery with small wounds. This trial assessed the effects of spinal analgesia versus intravenous patient-controlled analgesia (PCA) on neuroendocrine responses in that setting. METHODS: A randomized clinical trial was conducted with participation of patients undergoing laparoscopic colorectal surgery within a managed recovery programme. Consenting patients were allocated randomly to spinal analgesia or morphine PCA as primary postoperative analgesia. The primary outcome was interleukin (IL) 6 levels; secondary outcomes were levels of cortisol, glucose, insulin and other cytokines, pain scores, morphine use and length of hospital stay. Stress response analysis was conducted before operation, and 3, 6, 12, 24 and 48 h after surgery. RESULTS: Of 143 eligible patients, 133 were randomized and 120 completed the study. Baseline patient characteristics were similar in the two groups. There were no significant differences in median levels of insulin, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, interferon γ, tumour necrosis factor α or vascular endothelial growth factor between the spinal analgesia and PCA groups at any time point. Three hours after surgery (but at no other time point) median (i.q.r.) levels of cortisol (468 (329-678) versus 701 (429-820) nmol/l; P = 0.004) and glucose (6.1 (5.4-7.5) versus 7.0 (6.0-7.7) mmol/l; P = 0.012) were lower in the spinal analgesia group than in the PCA group. Median (i.q.r.) levels of total intravenous morphine were lower in the spinal analgesia group (10.0 (3.3-15.8) versus 45.5 (34.0-60.5) mg; P < 0.001). CONCLUSION: Spinal analgesia reduced early neuroendocrine responses and overall parenteral morphine use. REGISTRATION NUMBER: NCT01128088 (http://www.clinicaltrials.gov).

Time to adjuvant chemotherapy following colorectal cancer resection is associated with an improved survival.

AIM: Multicentre randomized trials have demonstrated equivalent long-term outcomes for open and laparoscopic resection of colon cancer. Some studies have indicated a possible survival advantage in certain patients undergoing laparoscopic resection. Patients who receive adjuvant chemotherapy in < 8 weeks following surgery can have an improved survival. METHOD: Data were collated for patients having an elective laparoscopic or open resection for non-metastatic colorectal cancer between October 2003 and December 2010 and subsequently having adjuvant chemotherapy. Survival analysis was conducted. RESULTS: In all, 209 patients received adjuvant chemotherapy following open (n = 76) or laparoscopic (n = 133) surgery. Median length of stay was 3 days with laparoscopic resection and 6 days with open resection (P < 0.0005). Median number of days to initiation of adjuvant chemotherapy was 52 with laparoscopic resection and 58 with open resection (P = 0.008). The 5-year overall survival was 89.6% in patients receiving chemotherapy in < 8 weeks after surgery, compared with 73.5% who started the treatment over 8 weeks (P = 0.016). The 5-year overall survival for those patients with a laparoscopic resection was 82.3% compared with 80.3% with an open resection (P = 0.049). CONCLUSION: There is an overall survival advantage when patients receive adjuvant chemotherapy < 8 weeks after surgery. Laparoscopic resection allows earlier discharge and, subsequently, earlier initiation of adjuvant chemotherapy.

Development of an absolute gas-counting capability for low to medium activities.

Pacific Northwest National Laboratory (PNNL) is developing a capability to measure the absolute activity concentration of gaseous radionuclides using length-compensated proportional-counting. This capability will enable the validation of low-level calibration standards for use in PNNL's new shallow underground laboratory. Two sets of unequal length proportional counters have been fabricated; one set has been fabricated using ultra-low background (ULB) electroformed copper and a second set fabricated from Oxygen-Free High-Conductivity Copper (OFHC).

A new shallow underground gas-proportional counting lab--first results and Ar-37 sensitivity.

A new ultra-low-background proportional counter was recently developed with an internal volume of 100 cm(3) and has been characterized at pressures from 1-10 atm with P-10 (90% Ar, 10% methane) gas. This design, along with a counting system providing event digitization and passive and active shielding, has been developed to complement a new shallow underground laboratory (30 m water-equivalent). Backgrounds and low-level reference materials have been measured, and system sensitivity for (37)Ar has been calculated.

A shallow underground laboratory for low-background radiation measurements and materials development.

Pacific Northwest National Laboratory recently commissioned a new shallow underground laboratory, located at a depth of approximately 30 meters-water-equivalent. This new addition to the small class of radiation measurement laboratories located at modest underground depths houses the latest generation of custom-made, high-efficiency, low-background gamma-ray spectrometers and gas proportional counters. This paper describes the unique capabilities present in the shallow underground laboratory; these include large-scale ultra-pure materials production and a suite of radiation detection systems. Reported data characterize the degree of background reduction achieved through a combination of underground location, graded shielding, and rejection of cosmic-ray events. We conclude by presenting measurement targets and future opportunities.

Transcriptional regulation of the gene encoding the 78-kD glucose-regulated protein GRP78 in mouse sertoli cells: binding of specific factor(s) to the GRP78 promoter.

We investigate the mechanism by which expression of the GRP78 gene is regulated using a mouse Sertoli cell line as an experimental system. We identify testosterone as a new inducer of the GRP78 gene in these cells. Furthermore, we show that despite their unusually low basal level of GRP78 mRNA, Sertoli cells retain the capacity to induce the GRP78 gene to high levels when challenged with the calcium ionophore A23187. Cellular factors present in whole-cell extracts isolated from Sertoli cells under noninduced and A23187-induced conditions bind specifically to a region of the GRP78 promoter previously identified as essential for maintenance of basal level expression and A23187 induction. We detect no difference in the binding of protein factors in the extracts prepared from noninduced versus induced cells. On the basis of this data, we propose models by which induction of the GRP78 gene may occur.

Nucleotide sequence of the chicken 5-aminolevulinate synthase gene.

5-Aminolevulinate synthase, the first and rate-controlling enzyme of heme biosynthesis, is regulated in the liver by the end-product heme. To study this negative control mechanism, we have isolated the chicken gene for ALA-synthase and determined the nucleotide sequence. The structural gene is 6.9 kb long and contains 10 exons. The transcriptional start site for ALA-synthase was determined by primer extension analysis. A fragment of 291 bp from the 5' flanking region including 34 bp of the first exon shows promoter activity when introduced upstream of a chicken histone H2B gene and injected into the nuclei of Xenopus laevis oocytes.

Complete nucleotide sequence of hepatic 5-aminolaevulinate synthase precursor.

Chick embryo liver mitochondrial matrix protein, 5-aminolaevulinate synthase, is synthesised initially as a larger cytosolic precursor. In this report we present the complete nucleotide sequence of a cDNA clone coding for the precursor together with corresponding confirmatory amino acid sequence of peptides derived from purified mature mitochondrial enzyme. The deduced amino acid sequence shows that the precursor consists of mature enzyme of 579 amino acids and an N-terminal extension of 56 amino acids. The latter presequence is highly basic in character as found with other mitochondrial preproteins.

Morphiceptin ( beta-casomorphin (1-4) amide): a peptide opioid antagonist in the field stimulated rat vas deferens.

The effect of Morphiceptin (H-Tyr-Pro-Phe-Pro-NH2) on opioid inhibition of field stimulated rat vas deferens (RVD) was studied. The morphiceptin was found to produce a weak inhibition of the twitch response of the RVD. In addition morphiceptin antagonized full agonists acting on the same receptor system (i.e. beta-endorphin selective antagonist for the delta receptor system of RVD by virtue of being a weak partial agonist.

N alpha-formyl-norleucyl-leucyl-phenylalanyl chloromethylketone. A possible covalent agonist of the N alpha-formyl-methionyl-peptide receptor.

N alpha-formyl-norleucyl-leucyl-phenylalanine-chloromethyl ketone is chemotactic for, and induces lysosomal enzyme release from rabbit peritoneal neutrophils over essentially the same range of concentrations as does the free acid form of the same peptide (N alpha-formyl-norleucyl-leucyl-phenylalanine-OH). The chloromethyl ketone derivative does however differ from the free acid in respect to its ability to interact with the neutrophil and cause deactivation or desensitization to cytochalasin B. Neutrophils preincubated in the cold with the chloromethyl ketone followed by washing have cytochalasin B sensitivity conferred upon them, as measured by the release of lysosomal enzymes. The degree of release induced by this pre-treatment appears to be related to the initial responsiveness of the cells. This is in contrast to the free acid where no cytochalasin B sensitivity is conferred under any circumstances. Thus, the chloromethyl ketone, unlike the free acid, appears to irreversibly activate the cell. Desensitization to the late addition of cytochalasin B is also significantly retarded when the chloromethyl ketone derivative is compared to the free acid form of the peptide. These studies suggest that the chloromethyl ketone derivative of the peptide may covalently interact with the neutrophil receptor.