High Background Levels Research Articles

Evaluation of intensity and pulse width of different moderators for designing a new diffractometer for protein crystals with large unit cells in J-PARC/MLF

We plan to design a high-resolution biomacromolecule neutron time-of-flight diffractometer, which allows us to collect data from crystals with unit cells above 250Å, in the materials and life science experimental facility at the Japan Proton Accelerator Research Complex. This new diffractometer can be used for a detailed analysis of large proteins such as membrane proteins and supermolecular complex. A quantitative comparison of the intensity and pulse width of a decoupled moderator (DM) against a coupled moderator (CM) considering the pulse width time resolution indicated that the DM satisfies the criteria for our diffractometer rather than the CM. The results suggested that a characteristic feature of the DM, i.e., narrow pulse width with a short tail, is crucial for the separation of Bragg reflections from crystals with large unit cells. On the other hand, it should be noted that the weak signals from the DM are buried under the high-level background caused by the incoherent scattering of hydrogen atoms, especially, in the case of large unit cells. We propose a profile-fitting integration method combined with the energy loss functions and a background subtraction method achieved by employing the statistics-sensitive nonlinear iterative peak-clipping algorithm.

Investigating the cellular fate of a DNA-targeted platinum-based anticancer agent by orthogonal double-click chemistry

Confocal fluorescence microscopy was used to study a platinum-based anticancer agent in intact NCI-H460 lung cancer cells. Orthogonal copper-catalyzed azide-alkyne cycloaddition (click) reactions were used to simultaneously determine the cell-cycle-specific localization of the azide-functionalized platinum-acridine agent 1 and monitor its effects on nucleic acid metabolism. Copper-catalyzed postlabeling showed advantages over copper-free click chemistry using a dibenzocyclooctyne (DIBO)-modified reporter dye, which produced high background levels in microscopic images and failed to efficiently label platinum adducts in chromatin. Compound 1 was successfully labeled with the fluorophore DIBO to yield 1* (characterized by in-line high-performance liquid chromatography/electrospray mass spectrometry). 1 and 1* show a high degree of colocalization in the confocal images, but the ability of 1* to target the (compacted) chromatin was markedly reduced, most likely owing to the steric bulk introduced by the DIBO tag. Nuclear platinum levels correlated inversely with the ability of the cells to synthesize DNA and cause cell cycle arrest, as confirmed by bivariate flow cytometry analysis. In addition, a decrease in the level of cellular transcription, shrinkage of the nucleolar regions, and redistribution of RNA into the cytosol were observed. Postlabeling in conjunction with colocalization experiments is a useful tool for studying the cell killing mechanism of this type of DNA-targeted agent.

GaiaRadial Velocity Spectrometer Performance

We present the initial performance of the Gaia Radial Velocity Spectrometer, providing an overview of its performance, which is essentially nominal in terms of spectral resolution, throughput and operation, except for the presence of unexpectedly high levels of scattered background. This is mainly Solar in origin, and reduces the limiting magnitude for radial velocity measurements by ∼1 magnitude to V ∼ 16. Radial velocity calibration accuracies are compliant with requirements.

Study of light mesons with WASA-at-COSY

The WASA detector, operating at the COSY facility in Julich (Germany) has been collecting data since 2007. The experiment allows to perform studies of light mesons, such as 0 , and rare decay processes, in order to perform precise measurements of branching ratios, determine Dalitz plot parameters, test symmetry and symmetry breaking, and evaluate transition form factors. In the experiments a proton or deuteron beam impinged on a pellet target of hydrogen or deuterium, which allows the reactions proton-proton (pp) or proton-deuteron (pd). A high-statistics sample of mesons has been collected: in the reaction pd → 3 He ,3 ×10 7 mesons were tagged at a beam energy of 1.0 GeV, while 5×10 8 mesons were produced in the reaction pp → pp at 1.4GeV. This corresponds to the production of 10 /s and 100 /s, respectively, for the two reaction processes. In the pp dataset a higher background level is found compared to the pd data set. In both cases, we identify the mesons by means of the missing mass derived from the recoil particles. A kinematic fit largely rejects the background in our analysis. The advantage in using the pp dataset is that the production of mesons is almost a factor of 10 higher than in the pd fusion to 3 He. As we plan to measure the branching ratios of very rare processes, high statistics is needed. A summary of the recent activity on the study of light mesons with WASA-at-COSY here is given.

Radiated BPF sound measurement of centrifugal compressor

A technique to measure radiated BPF sound from an automotive turbocharger compressor impeller is proposed in this paper. Where there are high-level background noises in the measurement environment, it is difficult to discriminate the target component from the background. Since the effort of measuring BPF sound was taken in a room with such condition in this study, no discrete BPF peak was initially found on the sound spectrum. Taking its directionality into consideration, a microphone covered with a parabolic cone was selected and using this technique, the discrete peak of BPF was clearly observed. Since the level of measured sound was amplified due to the area-integration effect, correction was needed to obtain the real level. To do so, sound measurements with and without a parabolic cone were conducted for the fixed source and their level differences were used as correction factors. Consideration is given to the sound propagation mechanism utilizing measured BPF as well as the result of a simple model experiment. The present method is generally applicable to sound measurements conducted with a high level of background noise.

Removal of Noise in Medical Imaging Data using Modified Decision based Adaptive Weight Algorithm

An effective filtering algorithmic program is planned for removing the salt and pepper noise at the various noise density position. Initial to discover the noise pixels, then completely different completely different} ways area unit practical to different noise densities. If noise density could be a smaller quantity than half-hour then, mean Filtering is applied to screeching image and if noise density is quite half-hour then, adaptive weight algorithmic program is applied to screeching image. Experimental results offer you a plan that this algorithmic program will suppress noise effectively. Changed call primarily based adaptive weight algorithmic program is developed for the removal of salt and pepper noise. It consists of 2 major steps, 1st to discover noise pixels in keeping with the correlations between image pixels, then use completely different ways supported the varied noise levels. For the low background level, neighborhood signal pixels mean methodology is adopted to get rid of noise and for the high background level, associate degree adaptive weight algorithmic program is employed. Experiments shows the planned algorithmic program has benefits over regularizing ways in terms of each edge preservation and noise removal, even for heavily infected image with background level as high as ninetieth. It still will get a big performance. Terms — PSNR (Peak Signal to Noise Ratio), salt and pepper noise; adaptive weight algorithms; noisy image; mean filtering.

How do background ozone concentrations affect the biosynthesis of rosmarinic acid in Melissa officinalis?

Lemon balm (Melissa officinalis; Lamiaceae) plants were exposed to background ozone (O3) dosages (80ppb for 5h), because high background levels of O3 are considered to be as harmful as episodic O3 peaks. Immediately at the end of fumigation the plants appeared visually symptomless, but necrotic lesions were observed later. The biosynthesis of rosmarinic acid (RA) comprises eight enzymes, among them phenylalanine ammonia-lyase (PAL), 4-coumarate:coenzyme A ligase (4CL), tyrosine aminotransferase (TAT) and rosmarinic acid synthase (RAS). The transcript levels of these genes have been investigated by quantitative RT-PCR. There was a quick up-regulation of all genes at 3h of O3 exposure, but at 24h from beginning of exposure (FBE) only RAS and PAL were up-regulated. The specific activity of RAS was closely correlated with a decrease of RA concentration in lemon balm leaves. The specific activity of PAL increased at 12h FBE to 163% in comparison to control levels. This work provides insight into the effect of O3 stress on the formation of the main phenolic ingredient of the pharmaceutically important plant M. officinalis.

How sensitive is Melissa officinalis to realistic ozone concentrations?

Lemon balm (Melissa officinalis, L.; Lamiaceae) was exposed to realistic ozone (O3) dosages (80 ppb for 5 h), because high background levels of O3 are considered to be as harmful as episodic O3 regimes. Temporal alterations of different ecophysiological, biochemical and structural parameters were investigated in order to test if this species can be considered as an O3-bioindicator regarding changes in background concentrations. At the end of ozone exposure, the plants did not exhibit any visible foliar symptoms, as only at microscopic level a small number of dead cells were found. Photosynthetic processes, however, were significantly affected. During and after the treatment, ozone induced a reduction in CO2 fixation capacity (up to 52% after 12 h from the beginning of the treatment) due to mesophyllic limitations. Intercellular CO2 concentration significantly increased in comparison to controls (+90% at the end of the post-fumigation period). Furthermore impairment of carboxylation efficiency (−71% at the end of the post-fumigation period compared to controls in filtered air) and membrane damage in terms of integrity (as demonstrated by a significant rise in solute leakage) were observed. A regulatory adjustment of photosynthetic processes was highlighted during the post-fumigation period by the higher values of qNP and (1-qP) and therefore suggests a tendency to reduce the light energy used in photochemistry at the expense of the capacity to dissipate the excess as excitation energy. In addition, the chlorophyll a/b ratio and the de-epoxidation index increased, showing a rearrangement of the pigment composition of the photosynthetic apparatus and a marked activation of photoprotective mechanisms.

Effects of full-scale beach renovation on fecal indicator levels in shoreline sand and water

Recolonization of enterococci, at a non-point source beach known to contain high background levels of bacteria, was studied after a full-scale beach renovation project. The renovation involved importation of new exogenous sand, in addition to infrastructure improvements. The study's objectives were to document changes in sand and water quality and to evaluate the relative contribution of different renovation activities towards these changes. These objectives were addressed: by measuring enterococci levels in the sand and fecal indicator bacteria levels (enterococci and fecal coliform) in the water, by documenting sediment characteristics (mineralogy and biofilm levels), and by estimating changes in observable enterococci loads. Analysis of enterococci levels on surface sand and within sediment depth cores were significantly higher prior to beach renovation (6.3–72 CFU/g for each sampling day) when compared to levels during and after beach renovation (0.8–12 CFU/g) (P < 0.01). During the renovation process, sand enterococci levels were frequently below detection limits (<0.1 CFU/g). For water, exceedances in the regulatory thresholds that would trigger a beach advisory decreased by 40% for enterococci and by 90% for fecal coliform. Factors that did not change significantly between pre- and post- renovation included the enterococci loads from animals (approx. 3 × 1011 CFU per month). Factors that were observed to change between pre- and post- renovation activities included: the composition of the beach sand (64% versus 98% quartz, and a significant decrease in biofilm levels) and loads from direct stormwater inputs (reduction of 3 × 1011 CFU per month). Overall, this study supports that beach renovation activities contributed to improved sand and water quality resulting in a 50% decrease of observable enterococci loads due to upgrades to the stormwater infrastructure. Of interest was that the change in the sand mineralogy also coincided with changes in biofilm levels. More work is needed to evaluate the relationships between beach sand mineralogy, biofilm characteristics, and the retention of fecal indicator bacteria in sand.

Raman and IR reflection micro‐spectroscopic study of Er:YAG laser treated permanent and deciduous human teeth

Permanent and deciduous human teeth treated by a dental Er‐doped yttrium‐aluminium‐garnet pulse laser (λ = 2940 nm) as well as by classical drilling tools under conditions typical of the clinical practice were studied by ultraviolet Raman and Fourier transform infrared (FTIR) reflection microspectroscopy. Enamel was analyzed by both spectroscopic methods, whereas dentine was studied only by FTIR reflection because of the high level of photoluminescence continuum background even when a wavelength of 325 nm was used in inelastic light scattering experiments. The applied energy and pulse frequency of the dental laser varied between 200 and 500 mJ and between 10 and 30 Hz, respectively. The most important result is that after the laser treatment, the hydroxyapatite structure in both permanent and deciduous enamel is preserved: the apatite Ca‐P‐O framework remains intact, and the content of channel OH‐ groups is not changed within experimental uncertainties. The calcium‐phosphate framework of dentine also exhibits negligible laser‐induced changes. The only alterations in enamel induced by laser as well as by mechanical drilling are reduction of the amount of CO32‐ in apatite and changes in the protein conformation. The laser impact on the organic material and carbonate groups is strongest for laser power of 8 W; for powers of 4 or 5 W, the combination of higher pulse energy and lower pulse frequency has less impact than the combination of lower energy and higher frequency. No differences between deciduous and permanent teeth in their resistivity to laser irradiation with λ = 2940 nm were detected. Copyright © 2013 John Wiley &amp; Sons, Ltd.

A multistep image analysis method to increase automated identification efficiency in immunohistochemical nuclear markers with a high background level

The “removal” of background from digital images (DIs) to identify only the objects of interest is difficult due to the overlapping color values of pixels of the nuclei and background. We outline a new automated procedure to quantify only immunohistochemically stained nuclear markers, despite the similar color of the background. This procedure was compared with the gold standard manual method and a previous method developed for low-background DIs.

Prenatal exposure to polychlorinated biphenyls and their hydroxylated metabolites is associated with motor development of three-month-old infants

BackgroundPolychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that are potentially toxic to the developing brain. Hydroxylated metabolites of PCBs (OH-PCBs) are suggested to be even more toxic. Little is known about their short-term effects on human health. ObjectivesTo determine whether prenatal background exposure to PCBs and OH-PCBs was associated with the motor development of three-month-old infants. MethodsNinety-seven mother–infant pairs participated in this Dutch, observational cohort study. We determined the concentrations of PCBs and OH-PCBs in cord blood samples. When the infants were three months old we evaluated their motor development by assessing the presence and performance of spontaneous movement patterns from video recordings. We calculated a Motor Optimality Score (MOS). The score could range from low (5) to high (28) optimality. We explored the correlations between PCB and OH-PCB levels and MOS. Subsequently, we tested whether the levels differed between infants with a low (<26) or high (≥26) MOS and whether the levels associated with detailed aspects of their motor repertoires. ResultsWe found several associations between PCB and OH-PCB levels and MOS, including detailed aspects of the early motor development. High 4-OH-PCB-107 levels were associated with a low MOS (P=.013). High PCB-187 levels were associated with reduced midline arm and leg movements (P=.047 and P=.043, respectively). High 4′-OH-PCB-172 levels were associated with more manipulation (P=.033). ConclusionsPrenatal exposure to high background levels of most PCBs and 4-OH-PCB-107 seems to impair early motor development, whereas only 4′-OH-PCB-172 showed the opposite.

Identification and replacement of proton‐contaminated real‐time ACE solar wind measurements

AbstractReal‐time solar wind speed measurements derived from measurements by the Solar Wind Electron, Proton, and Alpha Monitor (SWEPAM) aboard the Advanced Composition Explorer (ACE) satellite are critical to specifying and forecasting current space weather and its impacts. When solar energetic protons produce high background levels in SWEPAM, the real‐time solar wind speed measurements can be corrupted due to errors in the onboard algorithm. We analyzed 14 years of ACE real‐time solar wind data for the years 1998 through 2011 to determine how to identify the contaminated measurements and what proxy might be substituted for these corrupt data. We find that good criteria for flagging contaminated data are that (1) the measured solar wind speeds are below 305 km s–1, and (2) the &gt;10 MeV ion fluxes measured by the ACE Solar Isotope Spectrometer (SIS) are above 180 pfu. We also compare several potential proxies for the contaminated solar wind and determine that the best proxy depends on the last valid measured wind speed, vinitial, and the duration of the contamination period. For the first 25 h, the best proxy is simply vinitial. At later times, if vinitial &lt; 400 km s–1, then vinitial continues to be the best proxy, while if vinitial &gt; 400 km s–1, the best proxy is a linear function of the Kp geomagnetic index.

Batch and Continuous Mesophilic Anaerobic Digestion of Food Waste: Effect of Trace Elements Supplementation

Trace metals are essential for the enzyme cofactors involved in the biochemistry of methane formation and are needed in a balanced anaerobic digestion process. Food and kitchen waste generally contains low concentrations of trace elements, especially metals. As a consequence the anaerobic digestion process may result instable. The aim of this study is to evaluate the effect of metals addition on mesophilic anaerobic digestion of food waste, both in batch tests and in laboratory scale CSTR reactors. Batch anaerobic trials using source-separated food waste as substrate with inoculums of different origins were carried out under mesophilic conditions. Reactions were operated both with and without trace elements (Co, Mo, Ni, Se, W) supplementation. Supplementation with trace metals had either neutral or slightly negative effects with inoculums originating from reactors with a high background level of metals, such as those for the co-digestion of biowaste and waste activated sludge. For inoculums from reactors treating food waste only, which inherently contain low levels of trace metals, supplementation with these metals increased methane production. In particular, Mo concentrations in the range of 3-12 mg/kgTSfed and Se concentrations of 10 mg/kgTSfed increased methane production to as high as 30-40 %. Supplementation with a metal mixture (Co, Mo, Ni, Se, W) increased the methane production to the range 45-65 % for inoculums with low background concentrations of trace metals. These findings demonstrate the importance of Co, Mo, Ni, Se, W for high-performance anaerobic digestion process. Trace metals additions that showed the best batch results (100mgNi/kgTSfed, 100mgCo/kgTSfed, 6mgMo/kgTSfed, 10mgSe/kgTSfed, 10mgW/kgTSfed) were selected for CSTR experimentation. Performances of a continuous anaerobic digester fed with trace elements were compared to a “control reactor” fed with the same substrate but without metals addition. Preliminary CSTR results showed that metals addition allowed for a stable anaerobic digestion process at Organic Loading Rate greater than 3 kgVSfed m 3 •d but were not essential.

CD8+ TEMRA cells: higher background levels may predict delayed fracture healing.

CD8+ TEMRA cells: higher background levels may predict delayed fracture healing.

THU0204 The Positive Effect of Stringent Criteria for Purified Protein Derivation (PPD) Skin Test on Patients Treated with Certolizumab Pegol

BackgroundTreatment with biologics is associated with increased risk of tuberculosis (TB).1,2 Before starting an anti-TNF, patients (pts) should undergo screening for latent TB, including Purified Protein Derivation (PPD) skin test....

ACCUSA2: multi-purpose SNV calling enhanced by probabilistic integration of quality scores

Direct comparisons of assembled short-read stacks are one way to identify single-nucleotide variants. Single-nucleotide variant detection is especially challenging across samples with different read depths (e.g. RNA-Seq) and high-background levels (e.g. selection experiments). We present ACCUSA2 to identify variant positions where nucleotide frequency spectra differ between two samples. To this end, ACCUSA2 integrates quality scores for base calling and read mapping into a common framework. Our benchmarks demonstrate that ACCUSA2 is superior to a state-of-the-art SNV caller in situations of diverging read depths and reliably detects subtle differences among sample nucleotide frequency spectra. Additionally, we show that ACCUSA2 is fast and robust against base quality score deviations. ACCUSA2 is available free of charge to academic users and may be obtained from https://bbc.mdc-berlin.de/software. christoph.dieterich@mdc-berlin.de Supplementary data are available at Bioinformatics online.

Elimination of non-specific staining in immunohistochemistry of human liver tissues by modulation of antibody–antigen binding microenvironment

Immunohistochemistry (IHC) is a method of routine use in histopathology for the diagnosis and differentiated diagnosis of liver diseases. IHC staining in human hepatic tissue is often obstructed by the presence of non-specific antibody interactions, the cause of high background staining. Cognizant of previous encounters with high levels of background in human hepatic tissue when using polyclonal antibodies, the potential causes were systemattically investigated by testing the impact of different antibody variants and assay conditions. Firstly, IHC was performed on hepatic tissue with immunized and non-immunized polyclonal antibodies and it was demonstrated that immunized antibodies pervaded the samples with non-specific staining, while non-immunized antibodies produced insignificant background. Following, the primary antibody was co-incubated with different concentrations of protein blocks, acid/base solutions, crystalline ionic compounds, and combinations of these individual components in order to assess their potency in removing background staining. Optimization of these assay conditions revealed that background could be significantly reduced by the addition of sodium chloride to primary antibody solution and/or protein block to sodium azide-stabilized Tris-HCl buffer, while little beneficial effect was observed from co-incubating the primary antibody with non-serum protein block/goat serum, hydrochloric acid/sodium hydroxide, or a higher concentration of peroxidase block. Together, the results suggest that hepatic background in IHC is mainly attributed to strong ionic interactions between the light chains of polyclonal antibodies and polar molecules specifically prevalent in hepatic tissue, which can be reduced by increasing the ionic strength of the antibody–antigen reaction microenvironment. Thus, the findings can enhance the specificity of hepatic tissue immunoassays and improve IHC studies in human liver tissues using polyclonal antibodies.

Nearest neighbour diagnostic statistics on the accuracy of APT solute cluster characterisation

Diagnostic statistics and information theory techniques have been developed to investigate the accuracy to which solute clusters characterised in atom probe tomography (APT) data can reflect the true nature of the physical clusters in the original specimen. Simulated atom-probe datasets representing a range of atomic solute clustering within a pseudo-binary alloy upon an fcc aluminium lattice were generated for the study. The effectiveness of partitioning the APT-like simulated data based upon a binary classification defined by a distance threshold d max upon the kth nearest neighbour distance distribution was investigated. Information theory was also used to optimise the selection of the threshold d max. Analysis of variation was performed upon a factorial design of data simulations with low and high levels of: solute concentration; short-range order; and background to the mass-to-charge-state-ratio spectrum. This meta-analysis showed that the background levels have a significant compromising effect upon the binary classification in low solute systems with relatively low or random levels of clustering. Although the random clustering of higher solute concentrations is better analysed, significantly non-random clustering in both low and high solute concentrations is analysed well despite the presence of high levels of background. A meta-analysis of the binary classification upon a simulated dispersion of coherent precipitates within a similar matrix was also undertaken. Optimal k and d max parameters are likely a dependent upon the physical dimensions of precipitate size as well as the precipitate/matrix solute concentrations.

Safety and Immunogenicity of Neonatal Pneumococcal Conjugate Vaccination in Papua New Guinean Children: A Randomised Controlled Trial

BackgroundApproximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV) is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in a 0-1-2-month (neonatal) schedule with that of the routine 1-2-3-month (infant) schedule.MethodsWe randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV) at age 9 months. Serotype-specific serum IgG for PCV7 (VT) serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs) and proportions with concentration ≥0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV.ResultsWe enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001) and 9V (p<0.05) and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001) at age 2 months in the neonatal (one month post-dose2 PCV7) than in the infant group (one month post-dose1 PCV7). PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months.ConclusionsPCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months.Trial RegistrationClinicalTrials.gov NCT00219401NCT00219401