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The potential for malicious use of radiation, or radiation accidents could potentially lead to acute, high radiation doses to the public. Following acute accidental exposure to high doses of radiation, medical intervention is pivotal to the survivability of the patient, and the sooner the appropriate measures are taken the better the odds for survival. Early estimates of acute accidental radiation doses can be determined via biomarkers such as dicentric chromosome analysis or scenario reconstruction using computer software. However, both take valuable time and can be expensive. Increased frequencies of abnormal neutrophils in peripheral blood, referred to as pseudo Pelger-Huët anomalies (PPHAs), have been shown to be potential biomarkers of radiation exposure in several scenarios, including the 1958 Y-12 criticality accident and the radium dial painters. PPHAs are potentially a faster and cheaper quantitative biomarker for radiation exposure, and here they were evaluated in acutely exposed rhesus macaques. Peripheral blood smears from acutely exposed rhesus macaques were evaluated for the percentage of neutrophils that displayed the PPHA morphology using light microscopy. Irradiated animals received 0 to 8.5 Gy total body radiation using one of two strategies: (1) linear accelerator-produced 6 MV photons delivered at 80 cGy/minute; or (2) Cobalt 60-produced gamma irradiation delivered at 60 cGy/min. Zero dose animals were used to determine a baseline percentage of PPHAs, and blood smears taken periodically throughout the lifetime of exposed animals post-irradiation were used to determine the persistence and biokinetics of PPHAs. The baseline prevalence of the PPHA in rhesus macaques was determined to be 0.58 ± 0.46%. The dose-response curve with doses ranging from 0 Gy to 8.5 Gy (LD90/30) displayed a strong positive correlation between PPHA percentage and acute radiation dose (R2 of 0.88 p = 3.62 × 10−22). Statistically significant differences were found when animals were separated into dose cohorts of 0, 4, 6.4–6.5, and 8–8.5 Gy. The biokinetics model utilized only 4 Gy exposures and blood smears taken periodically over 3.1 years post-irradiation. PPHA morphology increases quickly following irradiation and appears stable over 3.1 years post-irradiation. PPHA morphology was confirmed to be present in rhesus macaques, a dose-response relationship was constructed, and it is stable over 3 years post-irradiation. This study demonstrates that PPHA analysis can be a fast and cheap method of biodosimetry. Future studies will work to determine the accuracy of dose determination and lower limits of detection. [ABSTRACT FROM AUTHOR]

Long-term survivors of brain irradiation can experience irreversible injury and cognitive impairment. T1-weighted and diffusion tensor magnetic resonance imaging (MRI) are used to evaluate brain volume and white matter (WM) microstructure in neurodevelopmental and neurodegenerative conditions. The goal of this study was to evaluate the long-term effects of single-dose total-body irradiation (TBI) or TBI with 5% partial-body sparing on brain volumetrics and WM integrity in macaques. We used MRI scans from a cohort of male rhesus macaques (age range, 3.6-22.8 years) to compare global and regional brain volumes and WM diffusion in survivors of TBI (T1-weighted, n = 137; diffusion tensor imaging, n = 121; dose range, 3.5-10 Gy) with unirradiated controls (T1-weighted, n = 48; diffusion tensor imaging, n = 38). In all regions of interest, radiation affected age-related changes in fractional anisotropy, which tended to increase across age in both groups but to a lesser extent in the irradiated group (interaction P <.01). Depending on the region of interest, mean diffusivity decreased or remained the same across age in unirradiated animals, whereas it increased or did not change in irradiated animals. The increases in mean diffusivity were driven by changes in radial diffusivity, which followed similar trends across age. Axial diffusivity did not differ by irradiation status. Age-related changes in relative volumes in controls reflected normal trends in humans, with increasing WM and decreasing gray matter until middle age. Cerebrospinal fluid (CSF) volume did not differ across age in controls. WM volume was lower and CSF volume was higher in young irradiated macaques. WM volume was similar between groups, and CSF volume lower in older irradiated macaques. Gray matter volume was unaffected by radiation. TBI results in delayed WM expansion and long-term disruption of WM integrity. Diffusion changes suggest that myelin injury in WM is a hallmark of late-delayed radiation-induced brain injury. [ABSTRACT FROM AUTHOR]

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach. [ABSTRACT FROM AUTHOR]

Objectives: Reliable biomarkers for renal fibrosis are needed for clinical care and for research. Existing non-invasive biomarkers are imprecise, which has limited their utility. Methods: We developed a method to quantify fibrosis by subject size-adjusted CT Hounsfield units. This was accomplished using CT measurements of renal cortex in previously irradiated non-human primates. Results: Renal cortex mean CT Hounsfield units that were adjusted for body size had a very good direct correlation with renal parenchymal fibrosis, with an area under the curve of 0.93. Conclusions: This metric is a promising and simple non-invasive biomarker for renal fibrosis. [ABSTRACT FROM AUTHOR]

Significance: Over the past 50 years, the mechanisms for O2 storage and transport have been determined quantitatively on distance scales from millimeters to tenths of nanometers and timescales from seconds to picoseconds. Recent Advances: In this review, I have described four key conclusions from work done by my group and our close colleagues. (i) O2 uptake by mammalian red cells is limited by diffusion through unstirred water layers adjacent to the cell surface and across cell-free layers adjacent to vessel walls. (ii) In most vertebrates, hemoglobins (Hbs) and myoglobins (Mbs), the distal histidine at the E7 helical position donates a strong hydrogen bond to bound O2, which selectively enhances O2 affinity, prevents carbon monoxide poisoning, and markedly slows autoxidation. (iii) O2 binding to mammalian Hbs and Mbs occurs by migration of the ligand through a channel created by upward rotation of the His(E7) side chain, capture in the empty space of the distal pocket, and then coordination with the ferroprotoporphyrin IX (heme) iron atom. (iv) The assembly of Mbs and Hbs occurs by formation of molten globule intermediates, in which the N- and C-terminal helices have almost fully formed secondary structures, but the heme pockets are disordered and followed by high-affinity binding of heme. Critical Issues: These conclusions indicate that there are often compromises between O2 transport function, holoprotein stability, and the efficiency of assembly. Future Directions: However, the biochemical mechanisms underlying these conclusions provide the framework for understanding globin evolution in greater detail and for engineering more efficient and stable globins. [ABSTRACT FROM AUTHOR]

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide. [ABSTRACT FROM AUTHOR]

Children with orthostatic intolerance (OI) have exaggerated decreases in heart rate variability (HRV) and suppression of baroreflex sensitivity (BRS) with standing. Accompanying brain transmitter and metabolite profiles are unknown. In this study, we used proton (1H) magnetic resonance spectroscopy (1H-MRS) to quantify markers of neuronal and glial integrity in a pilot study of children with OI compared with asymptomatic controls. Eighteen participants ages 10–18 yr were evaluated for blood pressure, heart rate (HR), and calculated indexes of autonomic function in supine and upright positions and, within an average of 2 wk, underwent 1H-MRS scans of dorsal medulla on a clinical 3T magnet while supine. As a result, of the 18 participants, 11 tested positive for OI and 7 did not. OI subjects exhibited higher HR and lower HRV and high-frequency α-index (HFα), an index of parasympathetic vagal tone, during standing compared with non-OI. HRV, sequence all (Seq All), high- and low-frequency (HFα and LFα) estimates of the spontaneous BRS decreased significantly, while BP variabilty increased significantly during standing only in subjects with OI. OI subjects had higher myoinositol (mIns) and total choline (tCho), markers of glial inflammation. Upright HFα and Seq All inversely correlated to supine tCho and mIns, respectively, independent of age and sex. In conclusions, in this pilot study, children with OI exhibit higher mIns and tCho in the dorsal medulla while supine that may reflect the well-established impairment in regulation of the autonomic nervous system upon standing. Neuroinflammation as an underlying cause or consequence of autonomic dysfunction is an intriguing possibility requiring further study. NEW & NOTEWORTHY (1H) magnetic resonance spectroscopy detected elevated markers of neuroinflammation in the dorsal medulla in children with impaired autonomic responses to head upright tilt. This first report of altered brain metabolites in this population provides a basis for future clinical studies using this methodology to aide in understanding complex autonomic disease states. [ABSTRACT FROM AUTHOR]

Presents the results of a survey of library users at Pennsylvania's Penn State University following the introduction of free laser printing. Tendency of students' printing to focus on their curricular needs; Sensitivity to the issue of wasteful printing; Willingness to pay for printing.

Presents information on a study which explained how librarians can understand, develop and use their creative thinking abilities and skills in the workplace. Creative thinking principles; Attributes to complement creative thinking; Creative thinking for librarians; Library organizational culture and creative thinking.

Reference site networks should consist of minimally disturbed sites that collectively characterize the ranges of natural settings within a region. Compromise between reference-quality and representativeness is required. We evaluated how tradeoffs between reference-quality and regional representativeness affected applicability, performance, and interpretation of multi-metric (MMI) and Observed/Expected (O/E) indices developed for streams in eastern China. We emphasized reference-quality by applying the most-stringent objective criteria and expert-judgment to select reference-group1 (G1). We emphasized representativeness by applying the least-stringent criteria to select reference-group2 (G2) sites from different strata based on watershed size. We balanced reference-quality and representativeness in G3 by applying intermediate stringent criteria from each watershed size stratum used previously. Increasing representativeness using G2 improved index applicability to almost more than twice the number of test sites than when reference-quality maximized using G1. Bias in O/E index was almost eliminated only when reference-quality and representativeness balanced using G3. MMIs developed when reference-quality maximized using G1 eliminated all bias and had the highest precision. High-quality reference with limited representativeness affected the metrics selected for inclusion in MMIs and restricted the sites to which both types of indices could be applied. A balanced approach worked best in this instance and similar approaches should be tested in other regions. [ABSTRACT FROM AUTHOR]

Agricultural, industrial and urban development have all contributed to increased salinity in streams and rivers, but the likely effects of future development and climate change are unknown. I developed two empirical models to estimate how these combined effects might affect salinity by the end of this century (measured as electrical conductivity, EC). The first model predicts natural background from static (e.g. geology and soils) and dynamic (i.e. climate and vegetation) environmental factors and explained 78% of the variation in EC. I then compared the estimated background EC with current measurements at 2001 sites chosen probabilistically from all conterminous USA streams. EC was more than 50% greater at 34% of these sites. The second model predicts deviation of EC from background as a function of human land use and environmental factors and explained 60% of the variation in alteration from background. I then predicted the effects of climate and land use change on EC at the end of the century by replacing dynamic variables with published projections of future conditions based on the A2 emissions scenario. By the end of the century, the median EC is predicted to increase from 0.319 mS cm -1 to 0.524 mS cm -1 with over 50% of streams having greater than 50% increases in EC and 35% more than doubling their EC. Most of the change is related to increases in human land use, with climate change accounting for only 12% of the increase. In extreme cases, increased salinity may make water unsuitable for human use, but widespread moderate increases are likely a greater threat to stream ecosystems owing to the elimination of low EC habitats. This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'. [ABSTRACT FROM AUTHOR]

Agricultural, industrial and urban development have all contributed to increased salinity in streams and rivers, but the likely effects of future development and climate change are unknown. I developed two empirical models to estimate how these combined effects might affect salinity by the end of this century (measured as electrical conductivity, EC). The first model predicts natural background from static (e.g. geology and soils) and dynamic (i.e. climate and vegetation) environmental factors and explained 78% of the variation in EC. I then compared the estimated background EC with current measurements at 2001 sites chosen probabilistically from all conterminous USA streams. EC was more than 50% greater at 34% of these sites. The second model predicts deviation of EC from background as a function of human land use and environmental factors and explained 60% of the variation in alteration from background. I then predicted the effects of climate and land use change on EC at the end of the century by replacing dynamic variables with published projections of future conditions based on the A2 emissions scenario. By the end of the century, the median EC is predicted to increase from 0.319 mS cm-1 to 0.524 mS cm-1 with over 50% of streams having greater than 50% increases in EC and 35% more than doubling their EC. Most of the change is related to increases in human land use, with climate change accounting for only 12% of the increase. In extreme cases, increased salinity may make water unsuitable for human use, but widespread moderate increases are likely a greater threat to stream ecosystems owing to the elimination of low EC habitats. [ABSTRACT FROM AUTHOR]

Iodine environmental measurements have consistently been validated in the literature using the standard material IAEA-375, soil collected approximately 160 miles northeast of Chernobyl, which is currently the only soil/sediment material with a certified 129 I activity. IAEA-375 has not been available for purchase since approximately 2010. Two other standard materials that are available (NIST SRM 4354, freshwater lake sediment and NIST SRM 4357, ocean sediment) have certified activities for a variety of radionuclides but not for 129 I. This paper reports a comparison of TIMS and AMS data for all three standards. [ABSTRACT FROM AUTHOR]

Spatial distributions of many freshwater invertebrates are associated with the concentration of total dissolved solids ( TDS) in streams (usually measured as specific electrical conductivity - EC). These patterns are presumably caused by taxon-specific effects of TDS on the maintenance of ion and water balance, which is energetically expensive and thus could affect fitness. However, no studies have assessed if TDS-related effects on fitness metrics, such as growth and survival, are predictive of distributions., We used stream-side, flow-through microcosms to experimentally determine how TDS concentration influenced three life-history performance measures (growth, mortality and emergence) of 13 species of aquatic insects. We then modelled the relationship between experimentally derived performance measures and both EC optima and minima estimated from field surveys., In the streamside experiment, we exposed taxa to stream water with naturally low (<25 μS cm−1) and moderate (>125 μS cm−1) EC for 83 days, controlling for differences in habitat, temperature, food availability and pH. We measured performance as the differences in specific growth rates, survival and adult emergence between the two treatments., Treatment effects on performance varied among taxa and with performance metric. Survival differences between treatments varied from 1 to 21 days, and specific growth rates differed by 0.07-1.5 day−1. Emergence success was less variable (>20% for only two taxa). Three taxa performed better in the low EC treatment, six in the moderate EC treatment, one had a mixed response and three taxa did not differ between treatments., The best model predicting field-derived EC optima included both survival and specific growth rate as predictors ( R2 = 0.68). Estimates of EC minima were not as strongly related to performance measures as were optima estimates. Taxa with greater performance in the moderate EC treatment had the highest EC optima, indicating that low TDS concentrations could restrict the distributions of taxa adapted to higher TDS concentrations. In contrast to taxa with higher EC preferences, taxa that can tolerate low EC environments will likely be increasingly stressed as stream TDS increases in response to climate and land-use change expected this century. [ABSTRACT FROM AUTHOR]

The poem "WEAVE OF THE DREAM KING" by John Olson is presented. First Line: THE LUNG EXHIBITS FOAM. I want to break the terrine's blowing mist. Last Line: heart, and our tendencies collapse into algebra.

A new isotope separator has been designed, constructed, and put into routine operation for separation of 133Xe providing a major advancement and significant cost reduction in preparation of this radioactive isotope. The design features and advantages are discussed that expedite high purity separation of relatively small quantities of this isotope. These advantages could be easily used to expedite separation of other shorter-lived radioactive isotopes. [ABSTRACT FROM AUTHOR]

Purpose: Premature musculoskeletal joint failure is a major source of morbidity among childhood cancer survivors. Radiation effects on synovial joint tissues of the skeleton are poorly understood. Our goal was to assess long-term changes in the knee joint from skeletally mature rats that received total-body irradiation while skeletal growth was ongoing. Materials and methods: 14 week-old rats were irradiated with 1, 3 or 7 Gy total-body doses of 18 MV X-rays. At 53 weeks of age, structural and compositional changes in knee joint tissues (articular cartilage, subchondral bone, and trabecular bone) were characterized using 7T MRI, nanocomputed tomography (nanoCT), microcomputed tomography (microCT), and histology. Results: T2 relaxation times of the articular cartilage were lower after exposure to all doses. Likewise, calcifications were observed in the articular cartilage. Trabecular bone microarchitecture was compromised in the tibial metaphysis at 7 Gy. Mild to moderate cartilage erosion was scored in the 3 and 7 Gy rats. Conclusions: Late degenerative changes in articular cartilage and bone were observed after total-body irradiation in adult rats exposed prior to skeletal maturity. 7T MRI, microCT, nanoCT, and histology identified potential prognostic indicators of late radiation-induced joint damage. [ABSTRACT FROM AUTHOR]

Antonini and Brunori's 1971 book "Hemoglobin and Myoglobin in Their Reactions with Ligands" was a truly remarkable publication that summarized almost 100 years of research on O 2 binding to these globins. Over the ensuing 50 years, ultra-fast laser photolysis techniques, high-resolution and time resolved X-ray crystallography, molecular dynamics simulations, and libraries of recombinant myoglobin (Mb) and hemoglobin (Hb) variants have provided structural interpretations of O 2 binding to these proteins. The resultant mechanisms provide quantitative descriptions of the stereochemical factors that govern overall affinity, including proximal and distal steric restrictions that affect iron reactivity and favorable positive electrostatic interactions that preferentially stabilize bound O 2. The pathway for O 2 uptake and release by Mb and subunits of Hb has been mapped by screening libraries of site-directed mutants in laser photolysis experiments. O 2 enters mammalian Mb and the α and β subunits of human HbA through a channel created by upward and outward rotation of the distal His at the E7 helical position, is non-covalently captured in the interior of the distal cavity, and then internally forms a bond with the heme Fe(II) atom. O 2 dissociation is governed by disruption of hydrogen bonding interactions with His (E7), breakage of the Fe(II)–O 2 bond, and then competition between rebinding and escape through the E7-gate. The structural features that govern the rates of both the individual steps and overall reactions have been determined and provide the framework for: (1) defining the physiological functions of specific globins and their evolution; (2) understanding the clinical features of hemoglobinopathies; and (3) designing safer and more efficient acellular hemoglobin-based oxygen carriers (HBOCs) for transfusion therapy, organ preservation, and other commercially relevant O 2 transport and storage processes. [ABSTRACT FROM AUTHOR]

In this article, the author discusses the technological changes in last ten years, as of 2014. The topics discussed include computing technology in 2002, the evolution of desktop computers with improved random access memory (RAM) and hard disk storage, making census maps from the data uploaded on information clouds, and compression and decompression of files downloaded from internet.

Abstract: We have investigated CO migration and binding in CuBMb, a copper-binding myoglobin double mutant (L29H–F43H), by using Fourier transform infrared spectroscopy and flash photolysis over a wide temperature range. This mutant was originally engineered with the aim to mimic the catalytic site of heme–copper oxidases. Comparison of the wild-type protein Mb and CuBMb shows that the copper ion in the distal pocket gives rise to significant effects on ligand binding to the heme iron. In Mb and copper-free CuBMb, primary and secondary ligand docking sites are accessible upon photodissociation. In copper-bound CuBMb, ligands do not migrate to secondary docking sites but rather coordinate to the copper ion. Ligands entering the heme pocket from the outside normally would not be captured efficiently by the tight distal pocket housing the two additional large imidazole rings. Binding at the Cu ion, however, ensures efficient trapping in CuBMb. The Cu ion also restricts the motions of the His64 side chain, which is the entry/exit door for ligand movement into the active site, and this restriction results in enhanced geminate and slow bimolecular CO rebinding. These results support current mechanistic views of ligand binding in hemoglobins and the role of the CuB in the active of heme–copper oxidases. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins. [Copyright &y& Elsevier]

Genome packaging for viruses with segmented genomes is often a complex problem. This is particularly true for influenza viruses and other orthomyxoviruses, whose genome consists of multiple negative-sense RNAs encapsidated as ribonucleoprotein (RNP) complexes. To better understand the structural features of orthomyxovirus RNPs that allow them to be packaged, we determined the crystal structure of the nucleoprotein (NP) of a fish orthomyxovirus, the infectious salmon anemia virus (ISAV) (genus Isavirus). As the major protein component of the RNPs, ISAV-NP possesses a bi-lobular structure similar to the influenza virus NP. Because both RNA-free and RNA-bound ISAV NP forms stable dimers in solution, we were able to measure the NP RNA binding affinity as well as the stoichiometry using recombinant proteins and synthetic oligos. Our RNA binding analysis revealed that each ISAV-NP binds ∼12 nts of RNA, shorter than the 24–28 nts originally estimated for the influenza A virus NP based on population average. The 12-nt stoichiometry was further confirmed by results from electron microscopy and dynamic light scattering. Considering that RNPs of ISAV and the influenza viruses have similar morphologies and dimensions, our findings suggest that NP-free RNA may exist on orthomyxovirus RNPs, and selective RNP packaging may be accomplished through direct RNA-RNA interactions. [ABSTRACT FROM AUTHOR]

Ecologically meaningful and scientifically defensible nutrient criteria are needed to protect the water quality of USA streams. Criteria based on our best understanding of naturally occurring nutrient concentrations would protect both water quality and aquatic biota. Previous approaches to predicting natural background nutrient concentrations have relied on some form of landscape categorization (e.g., nutrient ecoregions) to account for natural variability among water bodies. However, natural variation within these regions is so high that use of a single criterion can underprotect naturally occurring lownutrient streams and overprotect naturally occurring high-nutrient steams. We developed Random Forest models to predict how baseflow concentrations of total P (TP) and total N (TN) vary among western USA streams in response to continuous spatial variation in nutrient sources, sinks, or other processes affecting nutrient concentrations. Both models were relatively accurate (root mean square errors <12% of the range of observations for independent validation sites) and made better predictions than previous models of natural nutrient concentrations. However, the models were not very precise (TP model: r2 = 0.46, TN model: r2 = 0.23). An analysis of the sources of variation showed that our models accounted for most of the spatial variation in nutrient concentrations, and much of the imprecision was caused by temporal or measurement variation. We applied 2 methods to determine upper prediction limits that incorporated model error and could be used as site-specific nutrient criteria. These site-specific candidate nutrient criteria better accounted for natural variation among sites than did criteria based on regional average conditions, would increase protection for streams with naturally low nutrient concentrations, and specified more attainable conditions for those streams with naturally higher nutrient concentrations. [ABSTRACT FROM AUTHOR]

Context.-D-dimer is widely used for exclusion, or as an aid in diagnosis, of venous thromboembolism (VTE); however, the D-dimer assay methods available from manufacturers and the laboratory application of those methods vary widely. Objective.-To describe the current laboratory practice regarding the assay and reporting of D-dimer. Design.-Laboratories' D-dimer proficiency testing data were analyzed and laboratory practices regarding the performance and reporting of D-dimer were surveyed. Results.-Initial grading of D-dimer proficiency testing demonstrated high variability within and among methods. This variability continued to be present for several years after attempts to intervene. The number of laboratories using D-dimer to exclude VTE grew from 1500 in 2004 to more than 3500 in 2012. Survey and proficiency testing data demonstrated that 33% of laboratories changed the type or magnitude of units from that recommended by the manufacturer, a practice associated with as much as a 20- fold increase in the failure of proficiency testing. Many laboratories used a threshold for the exclusion of VTE that is higher than that recommended by the manufacturer. Many laboratories continue to use qualitative assays with insufficient sensitivity for exclusion of VTE. Conclusions.-There is considerable variability both within and among quantitative methods used to assay Ddimer by laboratories. Laboratory practice continues to vary widely regarding the type and magnitude of units reported and the setting of the threshold for the exclusion of VTE. Although improved, the variability continues despite initial efforts to intervene. [ABSTRACT FROM AUTHOR]

This work reports on a performance study of two numerical detectors that are particularly useful for infrasound arrays operating under windy conditions. The sum of squares of variance ratios (SSVR1)-proposed for detecting signals with frequency ranging from 1 to 10 Hz-is computed by taking the ratio of the squared sum of eigenvalues to the square of largest eigenvalue of the covariance matrix of the power spectrum. For signals with lower frequency between 0.015 and 0.1 Hz, SSVR2 is developed to reduce the detector's sensitivity to noise. The detectors' performances are graphically compared against the current method, the mean of cross correlation maxima (MCCM), using the receiver operating characteristics curves and three types of atmospheric infrasound, corrupted by Gaussian and Pink noise. The MCCM and SSVR2 detectors were also used to detect microbaroms from the 24 h-long infrasound data. It was found that the two detectors outperform the MCCM detector in both sensitivity and computational efficiency. For mine blasts corrupted by Pink noise (signal-to-noise ratio = -7 dB), the MCCM and SSVR1 detectors yield 62 and 88 % true positives when accepting 20% false positives. For an eight-sensor array, the speed gain is approximately eleven-fold for a 50 s long signal. [ABSTRACT FROM AUTHOR]

Background: The hallmark of atherosclerosis is the accumulation of plaque in vessel walls. This process is initiated when monocytic cells differentiate into macrophage foam cells under conditions with high levels of atherogenic lipoproteins. Vulnerable plaque can dislodge, enter the blood stream, and result in acute myocardial infarction and stroke. Imaging techniques such as cardiovascular magnetic resonance (CMR) provides one strategy to identify patients with plaque accumulation. Methods: We synthesized an atherosclerotic-targeting contrast agent (ATCA) in which gadolinium (Gd)-containing endohedrals were functionalized and formulated into liposomes with CD36 ligands intercalated into the lipid bilayer. In vitro assays were used to assess the specificity of the ATCA for foam cells. The ability of ATCA to detect atherosclerotic plaque lesions in vivo was assessed using CMR. Results: The ATCA was able to detect scavenger receptor (CD36)-expressing foam cells in vitro and were specifically internalized via the CD36 receptor as determined by focused ion beam/scanning electron microscopy (FIB-SEM) and Western blotting analysis of CD36 receptor-specific signaling pathways. The ATCA exhibited time-dependent accumulation in atherosclerotic plaque lesions of ApoE ?/? mice as determined using CMR. No ATCA accumulation was observed in vessels of wild type (C57/b6) controls. Non-targeted control compounds, without the plaque-targeting moieties, were not taken up by foam cells in vitro and did not bind plaque in vivo. Importantly, the ATCA injection was well tolerated, did not demonstrate toxicity in vitro or in vivo, and no accumulation was observed in the major organs. Conclusions: The ATCA is specifically internalized by CD36 receptors on atherosclerotic plaque providing enhanced visualization of lesions under physiological conditions. These ATCA may provide new tools for physicians to non-invasively detect atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Learning from mistakes or failures is the purpose of a laboratory's event management system. Laboratories that systematically and effectively learn from failures which occur especially from small mistakes and problems rather than from consequential adverse events, are rare. An effective event management program often requires a cultural sea change that emphasizes a process of detection and reporting of errors that is without reprisal. An approach to development of such an event management program is described in this article. Steps of eventmanagement including engagement of the staff, tools used, steps of evaluation, application to all elements of laboratory management, and culture change necessary are discussed. [ABSTRACT FROM AUTHOR]

Context.—Proper diagnosis and therapy of fibrinogen deficiency requires high-quality fibrinogen assays. Objective.—To assess the interlaboratory bias, precision, and grading of fibrinogen assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in coagulation. Design.—Two identical vials of normal plasma were sent to more than 3500 laboratories. Participants measured fibrinogen levels using local methods. Results.—Fifty different fibrinogen methods were evaluated. All-method bias was 8.3% (range of method-specific biases, 0.0%–27.0%) and all-method coefficient of variation was 7.7%(range of method-specific coefficients of variation, 0.7%–25.8%). After controlling for reagent/instrument type, mean fibrinogen levels were 11.6% higher for prothrombin time–based reagents compared to Clauss (P , .001), and coefficient of variation was 46% lower for mechanical endpoint instruments compared to photo-optical. Most testing events (97.4%) could be reliably graded as pass or fail using a target range of 620% from the method mean (total pass rate, 98.8%). Total fail rate was 3.0-fold lower for mechanical instruments compared to photo-optical (0.5% versus 1.5%, P = .001). Nonetheless many photo-optical methods had very high precision and very low fail rates. Conclusions.—Fibrinogen assays showed highly variable methodology and performance characteristics. Bias, precision, and grading were affected by the type of reagent or instrument used. [ABSTRACT FROM AUTHOR]

Two techniques for obtaining Russell–Saunders term symbols (terms) for equivalent electrons is presented. Both techniques are based on partitioning the n equivalent electrons into a set of α electrons and a set of β electrons. Fundamental tables are presented that give the number of states for the α or β electrons for all possible values M αL(M βL) and Sα(Sβ). One interpretation of these tables leads to the total number of states of the n equivalent electrons for values of L and S. From this the number of terms for L and S is easily determined. Another interpretation of the fundamental tables gives the maximum number of terms for n equivalent electrons with values of L and S. From this the actual number of terms is obtained. Examples of equivalent p, d, f, and g electrons are provided. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011 [ABSTRACT FROM AUTHOR]

Abstract: Fractionated partial or whole-brain irradiation (fWBI) is a widely used, effective treatment for primary and metastatic brain tumors, but it also produces radiation-induced brain injury, including cognitive impairment. Radiation-induced neural changes are particularly problematic for elderly brain tumor survivors who also experience age-dependent cognitive impairment. Accordingly, we investigated i] radiation-induced cognitive impairment, and ii] potential biomarkers of radiation-induced brain injury in a rat model of aging. Fischer 344 x Brown Norway rats received fractionated whole-brain irradiation (fWBI rats, 40Gy, 8 fractions over 4 weeks) or sham-irradiation (Sham-IR rats) at 12months of age; all analyses were performed at 26–30months of age. Spatial learning and memory were measured using the Morris water maze (MWM), hippocampal metabolites were measured using proton magnetic resonance spectroscopy (1H MRS), and hippocampal glutamate receptor subunits were evaluated using Western blots. Young rats (7–10months old) were included to control for age effects. The results revealed that both Sham-IR and fWBI rats exhibited age-dependent impairments in MWM performance; fWBI induced additional impairments in the reversal MWM. 1H MRS revealed age-dependent decreases in neuronal markers, increases in glial markers, but no detectable fWBI-dependent changes. Western blot analysis revealed age-dependent, but not fWBI-dependent, glutamate subunit declines. Although previous studies demonstrated fWBI-induced changes in cognition, glutamate subunits, and brain metabolites in younger rats, age-dependent changes in these parameters appear to mask their detection in old rats, a phenomenon also likely to occur in elderly fWBI patients >70years of age. [Copyright &y& Elsevier]

Context.--Hereditary and acquired deficiencies of antithrombin (AT), protein C (PC), and protein S (PS) are risk factors for venous thromboembolism. Proper diagnosis requires high-quality assays for these proteins. Objective.--To determine the accuracy and interlaboratory precision of AT, PC, and PS assays used by laboratories participating in the United States College of American Pathologists proficiency testing program in thrombophilia and to grade the performance of laboratories. Design.--Standardized normal plasma with assigned analyte values was sent in 2 separate challenges to participating laboratories. Participants measured AT, PC, and PS levels using local methods. Results.--When compared with the assigned values for the international standard, the order of assay accuracy from highest to lowest was AT activity, PC antigen, AT antigen, total PS antigen, PC activity, PS activity, and free PS antigen (range of assay bias, 2.6%-8.8%). The order of assay precision from highest to lowest was PC activity, AT activity, AT antigen, total PS antigen, PS activity, free PS antigen, and PC antigen (range of assay coefficient of variation, 6.1%-20.0%). Most testing events (87.8%) could be graded as pass or fail using a target range of 63 standard deviations from the method-specific mean. The pass rate was 98.2% for all AT, PC, and PS testing events combined. Conclusions.--Accuracy and precision were higher for AT assays and lower for PC and PS assays. It was feasible to grade individual laboratory performance. [ABSTRACT FROM AUTHOR]

The article discusses the evolution of the approach integrated by the Model Business Corporation Act (MBCA) to corporate governance in the U.S. It notes that amendments to the MBCA were directed to define the role of the board members while limiting their liabilities. It adds that in line with the several governance failures, accounting frauds and financial crises, the Committee on Corporate Laws of the American Bar Association Section of Business Law has moved from the traditional enabling statute to private ordering.

The unfolding of wild-type holomyoglobin in the ferric State (metMb) appears to be a Simple two- state process, even though hemichrome spectra are often observed and apoMb denaturation involves an intermediate. To resolve these discrepancies, we measured GuHCI-induced, equilibrium unfolding of five sperm whale metMb variants, which were selected to examine the relative importance of apoglobin stability and hemin affinity. Combined analysis of CD, Trp fluorescence, and Soret absorbance titration curves for all the variants requires a Six-State mechanism containing native (N), intermediate (I), and unfolded (U) states of apoMb and their hemin-bound counterparts, NH (holoMb), IH, and UH, respectively. The unfolding parameters for the apoMbs were obtained in independent experiments and then fixed in the analysis of the holoprotein data, where only the affinities of the apoglobin states for hemin were allowed to vary. This cofactor binding analysis applies generally to all globins and led to three specific conclusions. (I) The stability of holo-metMb is determined primarily by the high affinity (Kd 10-3M) of native apoMb (N) for hemin. (2) The partially unfolded intermediate with hemin bound (IH) has a hemichrome spectrum indicative of a bis- histidyl axial coordination and is seen clearly when the stability of the N state or its affinity for hemin is reduced. (3) Although the affinity of the intermediate for hemin (Kdl0-11M) is -` 100-fold lower than that for the native slate, free hemin can bind to it and promote the assembly of the holoprotein. [ABSTRACT FROM AUTHOR]

The FTIR spectra for alkyl isocyanides (CNRs) change from a single VCN band centered at ∼-2175 cm-1 to two peaks at ∼2075 and∼2125cm-1 upon binding to sperm whale myoglobin (Mb). The low- and high-frequency peaks have been assigned to in and Out conformations, respectively. In the in conformation, the ligand is pointing toward the protein interior, and the distal His64(E7) is in a closed position, donates a H-bond to the bound isocyano group, enhances back-bonding, and lowers the C-N bond order. In the out conformation, the ligand side chain points toward solvent through a channel opened by outward rotation of His64. Loss of positive polarity near the binding site causes an increase in C-N bond order. Support for this interpretation is threefold: (I) similar shifts to lower frequency occur for MbCO complexes when H-bond donation from His64(E7) occurs; (2) only one peak at ∼2125 cm-1, indicative of an apolar environment, is observed for CNRs bound to H64A or H64L Mb mutants or to chelated protoheme in soap micelles; and (3) the fraction of in conformation based on FTIR spectra correlates strongly with the fraction of geminate recombination after nanosecond laser photolysis. The in alkyl side chain conformation causes the photodissociated ligand to be "stuck" in the distal pocket, promoting internal rebinding, whereas the out conformation inhibits geminate recombination because part of the ligand is already in an open E7 channel, poised for rapid escape. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant aromatase inhibitor therapy has been reported to improve surgical outcomes for postmenopausal women with clinical stage II or III hormone receptor-positive breast cancer. A multicenter phase II clinical trial was conducted to investigate the value of this approach for US surgical practice. Study Design: One hundred fifteen postmenopausal women with >2 cm, estrogen receptor (ER) or progesterone receptor (PgR)−positive breast cancer were enrolled in a trial of 16 to 24 weeks of letrozole 2.5 mg daily before operation. Results: One hundred six patients were eligible for primary analysis, 96 underwent operations, 7 received chemotherapy after progressive disease, and 3 did not undergo an operation. Baseline surgical status was marginal for breast-conserving surgery (BCS) in 48 (45%), 47 were definitely ineligible for BCS (44%), and 11 were inoperable by standard mastectomy (10%). Overall Response Evaluation Criteria In Solid Tumors clinical response rate in the breast was 62%, with 12% experiencing progressive disease. Fifty percent underwent BCS, including 30 of 46 (65%) patients who were initially marginal for BCS and 15 of 39 (38%) patients who were initially ineligible for BCS. All 11 inoperable patients successfully underwent operations, including 3 (27%) who had BCS. Nineteen percent of patients undergoing mastectomy had a pathologic T1 tumor, suggesting that some highly responsive tumors were overtreated surgically. Conclusions: Neoadjuvant aromatase inhibitor improves operability and facilitates BCS, but there was considerable variability in responsiveness. Better techniques to predict response, determine residual tumor burden before operation, and greater willingness to attempt BCS in responsive patients could additionally improve the rate of successful BCS. [Copyright &y& Elsevier]

Objective. To determine if there is a hierarchy of improvement program adoption by hospitals and outline that hierarchy. Data Sources. Primary data were collected in the spring of 2007 via e-survey from 210 individuals representing 109 Minnesota hospitals. Secondary data from 2006 were assembled from the Leapfrog database. Study Design. As part of a larger survey, respondents were given a list of improvement programs and asked to identify those programs that are used in their hospital. Data Collection/Data Extraction. Rasch Model Analysis was used to assess whether a unidimensional construct exists that defines a hospital's ability to implement performance improvement programs. Linear regression analysis was used to assess the relationship of the Rasch ability scores with Leapfrog Safe Practices Scores to validate the research findings. Principal Findings. The results of the study show that hospitals have widely varying abilities in implementing improvement programs. In addition, improvement programs present differing levels of difficulty for hospitals trying to implement them. Our findings also indicate that the ability to adopt improvement programs is important to the overall performance of hospitals. Conclusions. There is a hierarchy of improvement programs in the health care context. A hospital's ability to successfully adopt improvement programs is a function of its existing capabilities. As a hospital's capability increases, the ability to successfully implement higher level programs also increases. [ABSTRACT FROM AUTHOR]

It is unclear how the human copper (Cu) chaperone Atox1 delivers Cu to metal-binding domains of Wilson and Menkes disease proteins in the cytoplasm. To begin to address this problem, we have characterized Cu(I) release from wild-type Atox1 and two point mutants (Met10Ala and Lys60Ala). The dynamics of Cu(I) displacement from holo-Atox1 were measured by using the Cu(l) chelator bicinchonic acid (BCA) as a metal acceptor. BCA removes Cu(I) from Atox1 in a three-step process involving the bimolecular formation of an initial Atox1-Cu-BCA complex followed by dissociation of Atox1 and the binding of a second BCA to generate apo-Atox1 and Cu-BCA2. Both mutants lose Cu(l) more readily than wild-type Atox1 because of more rapid and facile displacement of the protein from the Atoxl-Cu-BCA intermediate by the second BCA. Remarkably, Cu(l) uptake from solution by BCA is much slower than the transfer from holo-Atox1, presumably because of slow dissociation of DTT-Cu complexes. These results suggest that Cu chaperones play a key role in making Cu(l) rapidly accessible to substrates and that the activated protein-metal-chelator complex may kinetically mimic the ternary chaperone-metal-target complex involved in Cu(l) transfer in vivo. [ABSTRACT FROM AUTHOR]

We report the use of a high resolution magnetic resonance (MR) imaging technique to monitor the development and maturation of tissue-printed constructs in vivo. Layer-by- layer inkjet printing technology was used to fabricate three different tissue constructs on alginate/collagen gels: bovine aortic endothelial cell-printed (to represent soft tissue), human amniotic fluid-derived stem cell-printed (to represent hard tissue as they underwent osteogenic differentiation in vivo), and cell-free constructs (scaffold only). The constructs were subcutaneously implanted into athymic mice and regularly monitored using a 7 T magnetic resonance imaging (MRI) scanner. The three tissue construct types showed distinct image contrast characteristics due to the different tissue microstructures and biochemical compositions at various time points. In addition, changes in tissue microvasculature were examined with dynamic perfusion MRI. These results indicate that high resolution MRI is a promising method for noninvasive, long-term monitoring of the status of cell-printed construct growth, differentiation, and vascularization. [ABSTRACT FROM AUTHOR]

Context.—The international normalized ratio (INR) is widely used to monitor oral anticoagulation and to evaluate patients with coagulation disorders. Objective.—To examine the variability of the performance and reporting of the INR and to evaluate laboratory calculation of the INR. Design.—Between 1993 and 2003, laboratories participating in proficiency testing were surveyed. Participants provided the international sensitivity index and the mean normal prothrombin time used to calculate the INR. The INR was calculated from the data provided and compared with the INR reported to determine if the calculation was correct. Results.—Survey data regarding the INR collected between 1993 and 2003 demonstrate an improvement in reporting, using appropriate anticoagulant, using lower international sensitivity index reagents, and matching international sensitivity index and prothrombin time method. The all-method coefficient of variation of the INR improved from 18% to 5.8%. Among 3813 laboratories studied in 2002 and 2003, 4.1% miscalculated INR. Of 29 laboratories that reported investigation of the INR miscalculation, 11 (38%) reported correcting an INR that was being reported in patient results and that this error was corrected as a result of the study. Since beginning grading of the INR calculation, miscalculation of the INR has fallen to lessthan 1%. Conclusions.—Recommendations for change in laboratory practice made by consensus conferences are implemented during the course of many years. Difficulty calculating the INR was documented, and both the calculation and the variability in the reporting of the INR showed improvement. Proficiency testing, when closely evaluated and acted on, can have a direct impact on the quality of patient care. [ABSTRACT FROM AUTHOR]

Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes. [ABSTRACT FROM AUTHOR]

In heterogeneous system design, partitioning of the functional specifications into hardware (HW) and software (SW) components is an important procedure. Often, an HW platform is chosen, and the SW is mapped onto the existing partial solution, or the actual partitioning is performed in an ad hoc manner. The partitioning approach presented here is novel in that it uses Bayesian belief networks (BBNs) to categorize functional components into HW and SW classifications. The BBN's ability to propagate evidence permits the effects of a classification decision that is made about one function to be felt throughout the entire network. In addition, because BBNs have a belief of hypotheses as their core, a quantitative measurement as to the correctness of a partitioning decision is achieved. A methodology for automatically generating the qualitative structural portion of BBN and the quantitative link matrices is given. A case study of a programmable thermostat is developed to illustrate the BBN approach. The outcomes of the partitioning process are discussed and placed in a larger design context, which is called model-based codesign. [ABSTRACT FROM AUTHOR]

The author comments on the article "The Myth of the Shareholder Franchise," by Lucian Bebchuk. In the article, Bebchuk argues the failure of the presumed power of the shareholder franchise to hold directors accountable. Moreover, he proposes several changes to the system of corporate governance. He also comments on the inability of the current system of governance to impose an effective management of corporations.

We measured the mass and several potential indices of functional capacity of the leg and pectoral muscles through 21 d of age in chicks of three species of galliform birds and the domesticated turkey. The study was conducted to test the hypothesis that the growth rate of a tissue is inversely related to its capacity for mature function across species. We measured the proportion of protein and the activities of the catabolic enzymes citrate synthase (CS), pyruvate kinase (PK), and β-hydroxyacyl-CoA-dehydrogenase (HOAD) and estimated exponential growth rate (EGR) from growth increments. EGR was negatively related to proportion of protein, PK, and HOAD and positively related to CS activity. In a multiple regression, EGR was uniquely related only to proportion of protein; it was higher in pectoral muscles and increased in this order: wild turkey < pheasant < domestic turkey < chukar. Thus, among wild species, the muscles of smaller species grew more rapidly for a given proportion of protein, but domestication and selection for rapid growth and large muscle size in turkeys resulted in substantially elevated growth rate. When the proportion of protein was normalized by its maximum value for each species and muscle type, the relationship between EGR and normalized protein did not differ significantly among species or muscle type. Thus, if we accept the proportion of protein relative to the mature level as an index of functional capacity—presumably representing the assembly of the contractile apparatus—then growth rate is consistently inversely related to a muscle's capacity for mature function, that is, force generation. [ABSTRACT FROM AUTHOR]

Alpha hemoglobin-stabilizing protein (AHSP) is an erythroid protein that binds free α hemoglobin (αHb) to maintain its structure and limit its pro-oxidant activity. Prior studies have defined two different αHb·AHSP complexes. Binding of AHSP to Fe(II) αHb induces an unusual configuration in which the F helix of the globin becomes disordered and the heme ring becomes solvent-exposed. Over time, this intermediate oxidizes to form a stable hemichrome in which the proximal (F8) and distal (E7) histidines are coordinated to the heme iron atom. The addition of βHb to either Fe(II) or Fe(III) αHb·AHSP displaces AHSP to generate tetrameric (α2β2) HbA species. The biochemical properties and in vivo significance of the two αHb·AHSP complexes are poorly understood. Here we show that Fe(III) αHb·AHSP forms from auto-oxidation of oxygenated αHb bound to AHSP and that this process is greatly accelerated at physiologic temperature and oxygen pressures. In contrast to free Fe(III) αHb hemichromes, AHSP-bound Fe(III) αHb does not precipitate and can be recycled into functional HbA. This requires enzymatic reduction of AHSP-bound αHb, either prior to or after extraction by β subunits. In contrast, reaction of Fe(II) αHb-AHSP with βHb generates functional HbA directly. Our findings support a model in which AHSP can either stabilize αHb transiently en route to HbA formation during normal erythropoiesis or convert excessive free αHb into a more chemically inert state from which recovery of αHb is possible by redox cycling. [ABSTRACT FROM AUTHOR]

The article presents information on the origin of stark splitting in the initial photoproduct state of myoglobin. A microscopic structural description of the deceptively simple process of ligand photodissociation and recombination in myoglobin has begun to emerge with the application of low-temperature and time-resolved X-ray crystallography. Stretching frequencies and bond lengths obtained from DFT calculations of selected model systems, including co-ordinates.

The article analyzes whether scientific and technological education enables students to attain literacy needed as citizens. Science ought to play a civilizing role, particularly in the middle school, grades 7-10. However, if one examines typical contemporary middle-school science textbooks, it becomes clear that their content lacks the necessary details of the social context and fails to provide a framework for assessing social issues. Scientific knowledge is necessary but is not in itself sufficient for understanding the relationships among science, technology, society and the environment.

The major pathway for nitric oxide scavenging in red cells involves the direct reaction of the gas with HbO2 to form nitrate and the ferric form of the protein, metHb. Because both atoms of O2 are incorporated into nitrate, this process is called NO dioxygenation (NOD). The NOD reaction involves an initial, very rapid bimolecular addition of NO to bound O2 to form a transient Fe(III)–peroxynitrite complex, which can be observed spectrally at alkaline pH. This intermediate rapidly isomerizes at pH 7 (t1/2 ≤ 1 ms) to metHb and NO3−, which is nontoxic and readily transported out of red cells and excreted. The rate of NO consumption by intracellular HbO2 during normal blood flow is limited by diffusion up to and into the red cells and is too slow to interfere significantly with vasoregulation. In contrast, extracellular HbO2 is highly vasoconstrictive, and the resultant hypertension is a significant side effect of most hemoglobin-based blood substitutes. The major cause of this blood pressure effect seems to be the high rate of NO dioxygenation by cell-free HbO2, which can extravasate into the vessel walls and interfere directly with NO signaling between endothelial and smooth muscle cells. This interpretation is supported by a strong linear correlation between the magnitude of the blood pressure effect caused by infusion of cross-linked recombinant hemoglobin tetramers in vivo and the rate of NO dioxygenation by these proteins measured in vitro. [Copyright &y& Elsevier]

This study describes a method for determining the statistical confidence in estimates of direction-of-arrival and trace velocity stemming from signals present in atmospheric infrasound data. It is assumed that the signal source is far enough removed from the infrasound sensor array that a plane-wave approximation holds, and that multipath and multiple source effects are not present. Propagation path and medium inhomogeneities are assumed not to be known at the time of signal detection, but the ensemble of time delays of signal arrivals between array sensor pairs is estimable and corrupted by uncorrelated Gaussian noise. The method results in a set of practical uncertainties that lend themselves to a geometric interpretation. Although quite general, this method is intended for use by analysts interpreting data from atmospheric acoustic arrays, or those interested in designing and deploying them. The method is applied to infrasound arrays typical of those deployed as a part of the International Monitoring System of the Comprehensive Nuclear-Test-Ban Treaty Organization. [ABSTRACT FROM AUTHOR]

Summit and standard metabolism of winter-acclimatized dark-eyed juncos (Junco hyemalis) in MI average 6.95±0.17(SE) and 1.14±0.06 cm3 O2/min, respectively. Their “wet” thermal conductance at &les;−9°C is 18.3±0.67 in air and 46.3±1.48 mW/°C in He–O2. Citrate synthase (CS), phosphofructokinase (PFK), and hexokinase (HK) activities in junco pectoralis and mixed leg muscles suggest substantial aerobic and glycolytic capacities. However, relatively low activity of muscular 3-hydroxyacyl-CoA-dehydrogenase (HD) indicates limited capacity for fatty acid catabolism. CS, PFK, and HD activities in pectoralis exceed those in mixed leg muscles. The reverse is true for HK. [Copyright &y& Elsevier]

A recombinant Semliki Forest virus (SFV) RNA construct, SFV1-mCB2 RNA, was employed for the high-level expression of the murine CB2 (mCB2) cannabinoid receptor in baby hamster kidney cells. Biosynthetic radiolabel incorporation studies in concert with urea-sodium dodecylsulfate–polyacrylamide gel electrophoresis (urea-SDS–PAGE) and western immunoblotting revealed that two major proteins of approximately 26 and 40 kDa were produced by the construct. The 40 kDa product, but not the 26 kDa product, was glycosylated as determined by 2-deoxy-d-glucose incorporation and peptide-N-glycosidase F digestion analysis. Assessment of [3H]CP55940 ([3H]-(−)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol) binding data for membranes of cells transfected with SFV1-mCB2 RNA indicated a Kd of 0.35±0.04 nM and a Bmax of 24.4±2.7 pmol/mg. A rank order of binding affinities for cannabinoids, which paralleled that reported for native mCB2 receptors, was observed. The CB2 receptor-specific antagonist SR144528 (N-[(1S)-endo-1,3,3-trimethyl bicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide) blocked binding of [3H]CP55940, while the CB1 receptor-specific antagonist SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride] had a minimal effect. These results indicate that the recombinant receptor expressed from SFV1-mCB2 RNA exhibits properties, including ligand binding features, that are consistent with those for the native mCB2 receptor. However, the presence of both 26 and 40 kDa receptor species is consistent with alternative translation from two AUG start sites using the SFV1-mCB2 RNA expression system. [Copyright &y& Elsevier]

An important step in the design of subunit vaccines is the identification of promiscuous T helper cell epitopes in sets of disease-specific gene products. Most of the epitope prediction models are based on HLA-II peptide binding, which constitutes a major bottleneck in the natural selection of epitopes. Here we describe a computer model, TEPITOPE, that enables the systematic prediction of promiscuous peptide ligands for a broad range of HLA binding specificity. We show how to apply the TEPITOPE prediction model to identify T-cell epitopes, and provide examples of its successful application in the context of oncology, allergy, and infectious and autoimmune diseases. [Copyright &y& Elsevier]