Full Dynamic Range Research Articles

SU-E-I-11: A Novel High Resolution CT Imager for a Breast SPECT-CT System.

To evaluate the intrinsic characteristics of a new high resolution, large area, small bezel, digital imager developed for a dedicated SPECT-CT system for fully-3D mammotomographic imaging applications. A new flat panel digital imager was developed having 127μm pixels (identical to those in the Paxscan 2520) with an active 40×30cm area and 3200×2304 total pixels, which is well suited for pendant breast imaging close to the chest wall. The readout and driver ASIC TAB bonding pads were arranged on only two sides of the imager plate, to eliminate dead edge spacing. A special housing was developed to accommodate this imaging plate providing very narrow 8mm edges (bezels) on two orthogonal sides The TFT array imager was coated with 600μm thick micro-columnar CsI, which provides >90% absorption in the breast CT (60-80kVp) x-ray energy range. It provides better than 70% absorption for RQA5 (70kVp 21mm Al filter) x- ray radiation. The readout ASICs are connected to 14 bit A/D converters, and special readout ASICs with gain switching feature, which provide an additional 4bit virtual (2-3 effective) dynamic range. The MTF is ∼7.5% at the 3.9 lp/mm Nyquist frequency. The NPS curves continuously decrease with increasing spatial frequencies, characteristic of scintillator based imagers. The excellent DQE (0) measured at RQA5 is ∼75% in the 0.1-1mR dose range and ∼10% at the Nyquist frequency. The imager has excellent linearity over the full dynamic range, and high contrast images are readily acquired. The new 4030 flat panel imager is a high resolution, state of the art detector, ideal for breast imaging and other applications. This detector is included in the SPECT-CT device in development.

Statistical connection of binomial photon counting and photon averaging in high dynamic range beam-scanning microscopy

Data from photomultiplier tubes are typically analyzed using either counting or averaging techniques, which are most accurate in the dim and bright signal limits, respectively. A statistical means of adjoining these two techniques is presented by recovering the Poisson parameter from averaged data and relating it to the statistics of binomial counting from Kissick et al. [Anal. Chem. 82, 10129 (2010)]. The point at which binomial photon counting and averaging have equal signal to noise ratios is derived. Adjoining these two techniques generates signal to noise ratios at 87% to approaching 100% of theoretical maximum across the full dynamic range of the photomultiplier tube used. The technique is demonstrated in a second harmonic generation microscope.

Achieving sub electron noise in CCD systems by means of digital filtering techniques that lower 1/f pixel correlated noise

Scientific CCDs designed in thick high resistivity silicon (Si) are excellent detectors for astronomy, high energy and nuclear physics, and instrumentation. Many applications can benefit from CCDs ultra low noise readout systems. The present work shows how sub electron noise CCD images can be achieved using digital signal processing techniques. These techniques allow 0.4 electrons of noise at readout bandwidths of up to 10 Kpixels per second while keeping the full CCD spatial resolution and signal dynamic range.

Prediction of Muscle Energy States at Low Metabolic Rates Requires Feedback Control of Mitochondrial Respiratory Chain Activity by Inorganic Phosphate

The regulation of the 100-fold dynamic range of mitochondrial ATP synthesis flux in skeletal muscle was investigated. Hypotheses of key control mechanisms were included in a biophysical model of oxidative phosphorylation and tested against metabolite dynamics recorded by 31P nuclear magnetic resonance spectroscopy (31P MRS). Simulations of the initial model featuring only ADP and Pi feedback control of flux failed in reproducing the experimentally sampled relation between myoplasmic free energy of ATP hydrolysis (ΔGp = ΔGp o′+RT ln ([ADP][Pi]/[ATP]) and the rate of mitochondrial ATP synthesis at low fluxes (<0.2 mM/s). Model analyses including Monte Carlo simulation approaches and metabolic control analysis (MCA) showed that this problem could not be amended by model re-parameterization, but instead required reformulation of ADP and Pi feedback control or introduction of additional control mechanisms (feed forward activation), specifically at respiratory Complex III. Both hypotheses were implemented and tested against time course data of phosphocreatine (PCr), Pi and ATP dynamics during post-exercise recovery and validation data obtained by 31P MRS of sedentary subjects and track athletes. The results rejected the hypothesis of regulation by feed forward activation. Instead, it was concluded that feedback control of respiratory chain complexes by inorganic phosphate is essential to explain the regulation of mitochondrial ATP synthesis flux in skeletal muscle throughout its full dynamic range.

In situ quantification of noise as a function of signal in digital images

An efficient and accurate algorithm for determining the magnitude of noise as a function of signal in an arbitrary digital image is presented and demonstrated. The algorithm is robust and largely independent of the form of the image, returning the noise function with subcount error across the full dynamic range of a synthetic test image where noise of a known form has been added. The noise performance of a CCD under different image recording and processing conditions is examined using the algorithm. The effect of different noise functions on pattern-matching measurements of electronic structure by quantitative convergent beam electron diffraction is investigated.

Amplification and Demultiplexing in Insulin-regulated Akt Protein Kinase Pathway in Adipocytes

Akt plays a major role in insulin regulation of metabolism in muscle, fat, and liver. Here, we show that in 3T3-L1 adipocytes, Akt operates optimally over a limited dynamic range. This indicates that Akt is a highly sensitive amplification step in the pathway. With robust insulin stimulation, substantial changes in Akt phosphorylation using either pharmacologic or genetic manipulations had relatively little effect on Akt activity. By integrating these data we observed that half-maximal Akt activity was achieved at a threshold level of Akt phosphorylation corresponding to 5-22% of its full dynamic range. This behavior was also associated with lack of concordance or demultiplexing in the behavior of downstream components. Most notably, FoxO1 phosphorylation was more sensitive to insulin and did not exhibit a change in its rate of phosphorylation between 1 and 100 nm insulin compared with other substrates (AS160, TSC2, GSK3). Similar differences were observed between various insulin-regulated pathways such as GLUT4 translocation and protein synthesis. These data indicate that Akt itself is a major amplification switch in the insulin signaling pathway and that features of the pathway enable the insulin signal to be split or demultiplexed into discrete outputs. This has important implications for the role of this pathway in disease.

A Cylindrical-Core Fiber-Optic Oxygen Sensor Based on Fluorescence Quenching of a Platinum Complex Immobilized in a Polymer Matrix

A miniature (200 μm in diameter) cylindrical-core fiber-optic oxygen sensor has been developed for measuring rapid change in oxygen partial pressure (pO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> ). The fiber-optic sensing element is based on a cylindrical-core waveguide structure formed by coating a thin medical grade polymer sensing film that contains immobilized Pt(II) complexes on silica optical fiber. The performance such as sensitivity and time response of the fiber-optic oxygen sensors were evaluated using luminescence intensity measurement. To determine accurately the response time of the fiber optic oxygen sensors, a test chamber was used to provide rapid changes in the partial pressure of oxygen. The result showed that the time response (time-constant, τ) of this cylindrical-core fiber optic oxygen sensor is less than 50 ms. To our knowledge, this is the fastest such sensor of this size covering the full dynamic range of pO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> from 0 to 100 kPa.

Structural integrity of collagen and elastin in SynerGraft® decellularized–cryopreserved human heart valves

SynerGraft® (SG) decellularized–cryopreserved cardiac valve allografts have been developed to provide a valve replacement option that has reduced antigenicity, retained structural integrity, and the ability to be stored long-term until needed for implantation. However, it is critical to ensure that both the SG processing and cryopreservation of these allografts do not detrimentally affect the extracellular matrix architecture within the tissue. This study evaluates the effects of SG decellularization and subsequent cryopreservation on the extracellular matrix integrity of allograft heart valves. Human aortic and pulmonary valves were trisected, with one-third of each either left fresh (no further processing after dissection), decellularized, or decellularized and cryopreserved. Two-photon laser scanning confocal microscopy was used to visualize collagen and elastin in leaflets and conduits. The optimized percent laser transmission (OPLT) required for full dynamic range imaging of each site was determined, and changes in OPLT were used to infer changes in collagen and elastin signal intensity. Collagen fiber crimp period and collagen and elastin fiber diameter were measured in leaflet tissue. Statistically significant differences in OPLT and the dimensional characteristics of collagen and elastin in study groups were determined through single factor ANOVA. The majority of donor-aggregated average OPLT observations showed no statistically significant differences among all groups, indicating no difference in collagen or elastin signal strength. Morphometric analysis of collagen and elastin fibers revealed no significant alterations in treated leaflet tissues relative to fresh tissues. Collagen and elastin structural integrity within allograft heart valves are maintained through SynerGraft® decellularization and subsequent cryopreservation.

FDG-PET SUV Correlates with Expression of Genes Reflecting Proliferation, Metabolism, and Oncogene Activity in Mantle Cell Lymphoma (MCL),

Abstract 3670 Background:Mantle cell lymphoma (MCL) is a biologically heterogeneous disease with marked variation in clinical behavior. Tumor proliferation on gene expression profiling (GEP) is prognostic in MCL but is not available to the clinician. The % of Ki-67 expressing cells correlates with proliferation, but the test suffers inter-observer variability. We previously reported that SUV on FDG PET correlates to the tumor proliferation score (PS), the % Ki67 positive cells, and serum LDH levels in untreated MCL (Roschewski ASH 2010). Here, we expand this investigation to a larger cohort and present results of gene expression analysis of MCL lymph node biopsies in relation to FDG uptake. Methods:Untreated MCL patients underwent baseline PET/CT followed by a nodal biopsy. Analysis of the PET/CT scans was done by two experts in nuclear medicine who were blinded to the outcome of the patients and pathology findings. SUVnode and SUVmax normalized to body weight were recorded. For MCL patients, the expression of 18 proliferation signature genes were averaged to generate a PS as previously described (Rosenwald Cancer Cell 2003). The %Ki67 staining was calculated using computer-based image analysis software and recorded as the number of positive cells/total number of cells. Serum LDH on the day of treatment was recorded. Gene expression between tumor with high (> 5 SUVnode) and low (< 5 SUVnode) FDG uptake was compared. Gene expression and SUV as a continuous variable were also analyzed by Spearman correlation. Results:41 MCL patients were evaluated between September 2005 and March 2011. Median age was 58 years (41–73) and 78% of patients were male. All patients were stage IV and MIPI risk groups included 21 low, 15 intermediate and 5 high. PET/CT scans were available in 39, biopsies in 28, and adequate RNA for GEP in 27. The median SUVnode was 4.94 (1.81–12.89) and the median SUVmax 6.40 (2.22–17.5). SUVnode and SUVmax had virtually identical correlations to PS: r=0.45 (p < 0.016) and r=0.46 (p < 0.015). % Ki67 in MCL lymph node biopsies correlated with both SUVnode, r=0.58 (p < 0.002) and PS, r=0.59 (p < 0.001). LDH correlated with PS, r=0.55 (p < 0.002) but less so with SUVmax, r=0.35 (p < 0.03). We sought to determine which cellular processes correlate best with FDG avidity. We first separated MCL biopsies into two groups using the median SUV node. 88 probesets representing 79 genes were differentially expressed with a fold change ≥ 2. Of 32 upregulated genes, 14 were associated with cell proliferation and in Ingenuity Pathway analysis (IPA) the top network was cellular growth and proliferation. Next, we used Spearman correlation to better represent the full dynamic range of the FDG-PET measurement. 69 probesets genes were identified (FDR < 0.2) representing 61 genes, 47 of which were positively correlated with SUV PET. A key network function of these genes by IPA was carbohydrate and lipid metabolism. Among the genes with the highest correlation with SUV PET (rho > 0.72, p < 0.0001) were two members of the RAS Oncogene family: KRAS and RAB11A. There was also a remarkable representation of genes involved in protein homeostasis including PSMB5 that encodes the 26S proteasome subunit carrying the chymotrypsin like activity, Hsp40-family chaperones, and an ubiquitin conjugating enzyme (UBE2S). Finally, PRMT5 a protein arginine methyltransferase that has been shown to cooperate with cyclin D1 in promoting tumor growth also showed a high correlation with FDG-PET (rho = 0.65, p = 0.002). Conclusions:High FDG PET SUVs are typically seen in the quartile of patients with the highest tumor proliferation. Across all patients increasing SUV values correlate well with increased metabolism that intriguingly also includes the ubiquitin-proteasome system and PSMB5, the target of bortezomib. Thus, FDG PET might have some correlation with response to bortezomib treatment and should be further studied in this context. FDG PET integrates measures of proliferation and cellular metabolism and reflects disease specific activity of oncogenic pathways. Disclosures:No relevant conflicts of interest to declare.

18O-Labeled Proteome Reference as Global Internal Standards for Targeted Quantification by Selected Reaction Monitoring-Mass Spectrometry

Selected reaction monitoring (SRM)-MS is an emerging technology for high throughput targeted protein quantification and verification in biomarker discovery studies; however, the cost associated with the application of stable isotope-labeled synthetic peptides as internal standards can be prohibitive for screening a large number of candidate proteins as often required in the preverification phase of discovery studies. Herein we present a proof of concept study using an (18)O-labeled proteome reference as global internal standards (GIS) for SRM-based relative quantification. The (18)O-labeled proteome reference (or GIS) can be readily prepared and contains a heavy isotope ((18)O)-labeled internal standard for every possible tryptic peptide. Our results showed that the percentage of heavy isotope ((18)O) incorporation applying an improved protocol was >99.5% for most peptides investigated. The accuracy, reproducibility, and linear dynamic range of quantification were further assessed based on known ratios of standard proteins spiked into the labeled mouse plasma reference. Reliable quantification was observed with high reproducibility (i.e. coefficient of variance <10%) for analyte concentrations that were set at 100-fold higher or lower than those of the GIS based on the light ((16)O)/heavy ((18)O) peak area ratios. The utility of (18)O-labeled GIS was further illustrated by accurate relative quantification of 45 major human plasma proteins. Moreover, quantification of the concentrations of C-reactive protein and prostate-specific antigen was illustrated by coupling the GIS with standard additions of purified protein standards. Collectively, our results demonstrated that the use of (18)O-labeled proteome reference as GIS provides a convenient, low cost, and effective strategy for relative quantification of a large number of candidate proteins in biological or clinical samples using SRM.

A Propagation Analysis of Residual Distributions in Pipeline ADCs

This paper presents a propagation analysis of residual distributions in pipeline ADCs. It relies on the observation that the Frobenius-Perron operator which maps the input probability density of a pipeline stage into its output distribution admits a simple representation in the Fourier domain. It performs a decimation operation followed by a sign modulation operation on the Fourier coefficients of the input density. This representation is used to analyze the convergence of residual distributions to a uniform distribution as more stages are traversed. The analysis can also be used to show that quantization residuals become asymptotically independent. For quantization stages with redundant bits it is also shown that the span of the uniform distribution of quantization residuals need not coincide with the full ADC dynamic range.

Reply to Comment on ‘A first map of tropical Africa’s above-ground biomass derived fromsatellite imagery’

Biomass mapping using satellite imagery is a rapidly evolving field that has been greatlyfacilitated in recent years by the advent of LiDAR remote sensing coupled with co-locatedfield measurements. The biomass map of Africa that we published in 2008 did not takedirect advantage of coincident field and LiDAR measurements, as our more recent effortshave. The criticisms of our earlier map by Mitchard et al (2011 Environ. Res. Lett. 6049001) are duly noted and worthwhile, although they are also limited in several respectsthat we describe. Most notably, they assess our map with field data sets that are onlyrepresentative of a subset of conditions across the study domain, thus they notonly inadequately characterize undisturbed tropical forest regions but also thediverse disturbance dynamics that are captured in satellite imagery. We point outthe limitations of their assessment and focus on a way forward, moving beyondboth inadequate field sampling and remote sensing to an approach the capturesthe full range of dynamics by directly coupling field and satellite measurements.

Assimilation of streamflow and in situ soil moisture data into operational distributed hydrologic models: Effects of uncertainties in the data and initial model soil moisture states

We assess the potential of updating soil moisture states of a distributed hydrologic model by assimilating streamflow and in situ soil moisture data for high-resolution analysis and prediction of streamflow and soil moisture. The model used is the gridded Sacramento (SAC) and kinematic-wave routing models of the National Weather Service (NWS) Hydrology Laboratory’s Research Distributed Hydrologic Model (HL-RDHM) operating at an hourly time step. The data assimilation (DA) technique used is variational assimilation (VAR). Assimilating streamflow and soil moisture data into distributed hydrologic models is new and particularly challenging due to the large degrees of freedom associated with the inverse problem. This paper reports findings from the first phase of the research in which we assume, among others, perfectly known hydrometeorological forcing. The motivation for the simplification is to reduce the complexity of the problem in favour of improved understanding and easier interpretation even if it may compromise the goodness of the results. To assess the potential, two types of experiments, synthetic and real-world, were carried out for Eldon (ELDO2), a 795-km 2 headwater catchment located near the Oklahoma (OK) and Arkansas (AR) border in the U.S. The synthetic experiment assesses the upper bound of the performance of the assimilation procedure under the idealized conditions of no structural or parametric errors in the models, a full dynamic range and no microscale variability in the in situ observations of soil moisture, and perfectly known univariate statistics of the observational errors. The results show that assimilating in situ soil moisture data in addition to streamflow data significantly improves analysis and prediction of soil moisture and streamflow, and that assimilating streamflow observations at interior locations in addition to those at the outlet improves analysis and prediction of soil moisture within the drainage areas of the interior stream gauges and of streamflow at downstream cells along the channel network. To assess performance under more realistic conditions, but still under the assumption of perfectly known hydrometeorological forcing to allow comparisons with the synthetic experiment, an exploratory real-world experiment was carried out in which all other assumptions were lifted. The results show that, expectedly, assimilating interior flows in addition to outlet flow improves analysis as well as prediction of streamflow at stream gauge locations, but that assimilating in situ soil moisture data in addition to streamflow data provides little improvement in streamflow analysis and prediction though it reduces systematic biases in soil moisture simulation.

Joining distributed pattern processing and homeostatic plasticity in recurrent on-center off-surround shunting networks: Noise, saturation, short-term memory, synaptic scaling, and BDNF

The activities of neurons vary within small intervals that are bounded both above and below, yet the inputs to these neurons may vary many-fold. How do networks of neurons process distributed input patterns effectively under these conditions? If a large number of input sources intermittently converge on a cell through time, then a serious design problem arises: if cell activities are sensitive to large inputs, then why do not small inputs get lost in internal system noise? If cell activities are sensitive to small inputs, then why do they not all saturate at their maximum values in response to large inputs and thereby become incapable of processing analog differences in inputs across an entire network? Grossberg (1973) solved this noise-saturation dilemma using neurons that obey the membrane, or shunting, equations of neurophysiology interacting in recurrent and non-recurrent on-center off-surround networks, and showed how different signal functions can influence the activity patterns that the network stores in short-term memory. These results demonstrated that maintaining a balance between excitation and inhibition in a neural network is essential to process distributed patterns of inputs and signals without experiencing the catastrophies of noise or saturation. However, shunting on-center off-surround networks only guarantee that cell activities remain sensitive to the relative sizes of inputs and recurrent signals, but not that they will use the full dynamic range that each cell can support. Additional homeostatic plasticity mechanisms are needed to anchor the activities of networks to exploit their full dynamic range. This article shows how mechanisms of synaptic scaling can be incorporated within recurrent on-center off-surround networks in such a way that their pattern processing capabilities, including the ability to make winner-take-all decisions, is preserved. This model generalizes the synaptic scaling model of van Rossum, Bi, & Turrigiano (2000) for a single cell to a pattern-processing network of shunting cells that is capable of short-term memory storage, including a representation of how BDNF may homeostatically scale the strengths of excitatory and inhibitory synapses in opposite directions.

Pleiotropic and Age-dependent Effects of Decreased Protein Modification by O-Linked N-Acetylglucosamine on Pancreatic β-Cell Function and Vascularization

The hexosamine biosynthesis pathway (HBP) regulates the post-translational modification of nuclear and cytoplasmic protein by O-linked N-acetylglucosamine (O-GlcNAc). Numerous studies have demonstrated increased flux through this pathway contributes to the development of β-cell dysfunction. The effect of decreased O-GlcNAc on the maintenance of normal β-cell function, however, is not well understood. We studied transgenic mice that over express β-N-acetylglucosaminidase (O-GlcNAcase), an enzyme that catalyzes the removal of O-GlcNAc from proteins, in the pancreatic β-cell under control of the rat insulin promoter. 3-4-Month-old O-GlcNAcase transgenic mice have higher glucose excursions with a concomitant decrease in circulating insulin levels, insulin mRNA levels, and total islet insulin content. In older (8-9-month-old) O-GlcNAcase transgenic mice glucose tolerance is no longer impaired. This is associated with increased serum insulin, islet insulin content, and insulin mRNA in the O-GlcNAcase transgenic mice. These improvements in β-cell function with aging are associated with increased angiogenesis and increased VEGF expression, with parallel increases in activation of Akt and expression of PGC1α. The biphasic effects as a function of age are consistent with published observations of mice with increased O-GlcNAc in islets and demonstrate that O-GlcNAc signaling exerts multiple effects on both insulin secretion and islet survival.

Deep and Highly Sensitive Proteome Coverage by LC-MS/MS Without Prefractionation

In-depth MS-based proteomics has necessitated fractionation of either proteins or peptides or both, often requiring considerable analysis time. Here we employ long liquid chromatography runs with high resolution coupled to an instrument with fast sequencing speed to investigate how much of the proteome is directly accessible to liquid chromatography-tandem MS characterization without any prefractionation steps. Triplicate single-run analyses identified 2990 yeast proteins, 68% of the total measured in a comprehensive yeast proteome. Among them, we covered the enzymes of the glycolysis and gluconeogenesis pathway targeted in a recent multiple reaction monitoring study. In a mammalian cell line, we identified 5376 proteins in a triplicate run, including representatives of 173 out of 200 KEGG metabolic and signaling pathways. Remarkably, the majority of proteins could be detected in the samples at sub-femtomole amounts and many in the low attomole range, in agreement with absolute abundance estimation done in previous works (Picotti et al. Cell, 138, 795–806, 2009). Our results imply an unexpectedly large dynamic range of the MS signal and sensitivity for liquid chromatography-tandem MS alone. With further development, single-run analysis has the potential to radically simplify many proteomic studies while maintaining a systems-wide view of the proteome.

Increased Selectivity, Analytical Precision, and Throughput in Targeted Proteomics

Proteomics is gradually complementing large shotgun qualitative studies with hypothesis-driven quantitative experiments. Targeted analyses performed on triple quadrupole instruments in selected reaction monitoring mode are characterized by a high degree of selectivity and low limit of detection; however, the concurrent analysis of multiple analytes occurs at the expense of sensitivity because of reduced dwell time and/or selectivity due to limitation to a few transitions. A new data acquisition paradigm is presented in which selected reaction monitoring is performed in two ways to simultaneously quantify and confirm the identity of the targeted peptides. A first set of primary transitions is continuously monitored during a predetermined elution time window to precisely quantify each peptide. In addition, a set of six to eight transitions is acquired in a data-dependent event, triggered when all the primary transitions exceed a preset threshold. These additional transitions are used to generate composite tandem mass spectra to formally confirm the identity of the targeted peptides. This technique was applied to analyze the tryptic digest of a yeast lysate to demonstrate the performance of the technique. We showed a limit of detection down to tens of attomoles injected and a throughput exceeding 6000 transitions in one 60-min experiment. The technique was integrated into a linear work flow, including experimental design, data acquisition, and data evaluation, enabling large scale proteomic studies.

Time of flight mass spectrometry for quantitative data analysis in fast transient studies using a Temporal Analysis of Products (TAP) reactor

A Time of flight (ToF) mass spectrometer suitable in terms of sensitivity, detector response and time resolution, for application in fast transient Temporal Analysis of Products (TAP) kinetic catalyst characterization is reported. Technical difficulties associated with such application as well as the solutions implemented in terms of adaptations of the ToF apparatus are discussed. The performance of the ToF was validated and the full linearity of the specific detector over the full dynamic range was explored in order to ensure its applicability for the TAP application. The reported TAP-ToF setup is the first system that achieves the high level of sensitivity allowing monitoring of the full 0-200 AMU range simultaneously with sub-millisecond time resolution. In this new setup, the high sensitivity allows the use of low intensity pulses ensuring that transport through the reactor occurs in the Knudsen diffusion regime and that the data can, therefore, be fully analysed using the reported theoretical TAP models and data processing.

The C iv linewidth distribution for quasars and its implications for broad-line region dynamics and virial mass estimation

We perform an extensive analysis of the Civ line in three large spectroscopic surveys of quasars. Differing approaches for fitting the Civ line can be found in the literature, and we compare the most common methods to highlight the relative systematics associated with each. We develop a line fitting procedure and apply it to the Civ line in spectra from the SDSS, 2QZ and 2SLAQ surveys. Our results are compared with a previous study of the Mgii line in the same sample. Civ tends to be broader than the Mgii line in spectra that have both, and the average ratio between the lines is consistent with a simplistic model for a photoionised, virialised and stratified broad-line region. There is a statistically significant correlation between the widths of the Civ and Mgii lines. However, the correlation is weak, and the scatter around a best fit is only marginally less than the full dynamic range of line widths. Motivated by previous work, we examine the dispersion in the distribution of Civ line widths. We find that the dispersion in Civ line widths is essentially independent of both redshift and luminosity. This is in stark contrast to the Mgii line, which shows a strong luminosity dependence. Finally we consider our results in terms of their implications for virial black hole mass estimation. The inconsistency between Mgii and Civ line widths in single spectra, combined with the differing behaviour of the Mgii and Civ line width distributions, indicates that there must be an inconsistency between Mgii and Civ virial mass estimators. Furthermore, the level of intrinsic dispersion in Mgii and Civ line widths contributes less dynamic range to virial mass estimates than the error associated with the estimates. The indication is that the line width term in these UV virial mass estimators may be essentially irrelevant with respect to the typical uncertainty on a mass estimate.

A compact time-resolved system for near infrared spectroscopy based on wavelength space multiplexing

We designed and developed a compact dual-wavelength and dual-channel time-resolved system for near-infrared spectroscopy studies of muscle and brain. The system employs pulsed diode lasers as sources, compact photomultipliers, and time-correlated single photon counting boards for detection. To exploit the full temporal and dynamic range of the acquisition technique, we implemented an approach based on wavelength space multiplexing: laser pulses at the two wavelengths are alternatively injected into the two channels by means of an optical 2×2 switch. In each detection line (i.e., in each temporal window), the distribution of photon time-of-flights at one wavelength is acquired. The proposed approach increases the signal-to-noise ratio and avoids wavelength cross-talk with respect to the typical approach based on time multiplexing. The instrument was characterized on tissue phantoms to assess its properties in terms of linearity, stability, noise, and reproducibility. Finally, it was successfully tested in preliminary in vivo measurements on muscle during standard cuff occlusion and on the brain during a motor cortex response due to hand movements.