Mixed Linear/Square-Root Encoded Single-Slope Ramp Provides Low-Noise ADC with High Linearity for Focal Plane Arrays

Single-slope analog-to-digital converters (ADCs) are particularly useful for onchip digitization in focal plane arrays (FPAs) because of their inherent monotonicity, relative simplicity, and efficiency for column-parallel applications, but they are comparatively slow. Squareroot encoding can allow the number of code values to be reduced without loss of signal-to-noise ratio (SNR) by keeping the quantization noise just below the signal shot noise. This encoding can be implemented directly by using a quadratic ramp. The reduction in the number of code values can substantially increase the quantization speed. However, in an FPA, the fixed pattern noise (FPN) limits the use of small quantization steps at low signal levels. If the zero-point is adjusted so that the lowest column is onscale, the other columns, including those at the center of the distribution, will be pushed up the ramp where the quantization noise is higher. Additionally, the finite frequency response of the ramp buffer amplifier and the comparator distort the shape of the ramp, so that the effective ramp value at the time the comparator trips differs from the intended value, resulting in errors. Allowing increased settling time decreases the quantization speed, while increasing the bandwidth increases the noise. The FPN problem is solved by breaking the ramp into two portions, with some fraction of the available code values allocated to a linear ramp and the remainder to a quadratic ramp. To avoid large transients, both the value and the slope of the linear and quadratic portions should be equal where they join. The span of the linear portion must cover the minimum offset, but not necessarily the maximum, since the fraction of the pixels above the upper limit will still be correctly quantized, albeit with increased quantization noise. The required linear span, maximum signal and ratio of quantization noise to shot noise at high signal, along with the continuity requirement, determines the number of code values that must be allocated to each portion. The distortion problem is solved by using a lookup table to convert captured code values back to signal levels. The values in this table will be similar to the intended ramp value, but with a correction for the finite bandwidth effects. Continuous-time comparators are used, and their bandwidth is set below the step rate, which smoothes the ramp and reduces the noise. No settling time is needed, as would be the case for clocked comparators, but the low bandwidth enhances the distortion of the non-linear portion. This is corrected by use of a return lookup table, which differs from the one used to generate the ramp. The return lookup table is obtained by calibrating against a stepped precision DC reference. This results in a residual non-linearity well below the quantization noise. This method can also compensate for differential non-linearity (DNL) in the DAC used to generate the ramp. The use of a ramp with a combination of linear and quadratic portions for a single-slope ADC is novel. The number of steps is minimized by keeping the step size just below the photon shot noise. This in turn maximizes the speed of the conversion. High resolution is maintained by keeping small quantization steps at low signals, and noise is minimized by allowing the lowest analog bandwidth, all without increasing the quantization noise. A calibrated return lookup table allows the system to maintain excellent linearity

Separable Neural Components in the Processing of Black and White Faces

In a study of the neural components of automatic and controlled social evaluation, White participants viewed Black and White faces during event-related functional magnetic resonance imaging. When the faces were presented for 30 ms, activation in the amygdala—a brain region associated with emotion—was greater for Black than for White faces. When the faces were presented for 525 ms, this difference was significantly reduced, and regions of frontal cortex associated with control and regulation showed greater activation for Black than White faces. Furthermore, greater race bias on an indirect behavioral measure was correlated with greater difference in amygdala activation between Black and White faces, and frontal activity predicted a reduction in Black-White differences in amygdala activity from the 30-ms to the 525-ms condition. These results provide evidence for neural distinctions between automatic and more controlled processing of social groups, and suggest that controlled processes may modulate automatic evaluation.Psycholog

Fast, High-Precision Readout Circuit for Detector Arrays

The GEO-CAPE mission described in NASA's Earth Science and Applications Decadal Survey requires high spatial, temporal, and spectral resolution measurements to monitor and characterize the rapidly changing chemistry of the troposphere over North and South Americas. High-frame-rate focal plane arrays (FPAs) with many pixels are needed to enable such measurements. A high-throughput digital detector readout integrated circuit (ROIC) that meets the GEO-CAPE FPA needs has been developed, fabricated, and tested. The ROIC is based on an innovative charge integrating, fast, high-precision analog-to-digital circuit that is built into each pixel. The 128128-pixel ROIC digitizes all 16,384 pixels simultaneously at frame rates up to 16 kHz to provide a completely digital output on a single integrated circuit at an unprecedented rate of 262 million pixels per second. The approach eliminates the need for off focal plane electronics, greatly reducing volume, mass, and power compared to conventional FPA implementations. A focal plane based on this ROIC will require less than 2 W of power on a 11-cm integrated circuit. The ROIC is fabricated of silicon using CMOS technology. It is designed to be indium bump bonded to a variety of detector materials including silicon PIN diodes, indium antimonide (InSb), indium gallium arsenide (In- GaAs), and mercury cadmium telluride (HgCdTe) detector arrays to provide coverage over a broad spectral range in the infrared, visible, and ultraviolet spectral ranges

A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus causing vesicular oral or genital skin lesions, meningitis and other diseases particularly harmful in immunocompromised individuals. To comprehensively investigate the complex interaction between HSV-1 and its host we combined two genome-scale screens for host factors (HFs) involved in virus replication. A yeast two-hybrid screen for protein interactions and a RNA interference (RNAi) screen with a druggable genome small interfering RNA (siRNA) library confirmed existing and identified novel HFs which functionally influence HSV-1 infection. Bioinformatic analyses found the 358 HFs were enriched for several pathways and multi-protein complexes. Of particular interest was the identification of Med23 as a strongly anti-viral component of the largely pro-viral Mediator complex, which links specific transcription factors to RNA polymerase II. The anti-viral effect of Med23 on HSV-1 replication was confirmed in gain-of-function gene overexpression experiments, and this inhibitory effect was specific to HSV-1, as a range of other viruses including Vaccinia virus and Semliki Forest virus were unaffected by Med23 depletion. We found Med23 significantly upregulated expression of the type III interferon family (IFN-λ) at the mRNA and protein level by directly interacting with the transcription factor IRF7. The synergistic effect of Med23 and IRF7 on IFN-λ induction suggests this is the major transcription factor for IFN-λ expression. Genotypic analysis of patients suffering recurrent orofacial HSV-1 outbreaks, previously shown to be deficient in IFN-λ secretion, found a significant correlation with a single nucleotide polymorphism in the IFN-λ3 (IL28b) promoter strongly linked to Hepatitis C disease and treatment outcome. This paper describes a link between Med23 and IFN-λ, provides evidence for the crucial role of IFN-λ in HSV-1 immune control, and highlights the power of integrative genome-scale approaches to identify HFs critical for disease progression and outcome

Taking the First Steps towards a Standard for Reporting on Phylogenies: Minimum Information about a Phylogenetic Analysis (MIAPA)

In the eight years since phylogenomics was introduced as the intersection of genomics and phylogenetics, the field has provided fundamental insights into gene function, genome history and organismal relationships. The utility of phylogenomics is growing with the increase in the number and diversity of taxa for which whole genome and large transcriptome sequence sets are being generated. We assert that the synergy between genomic and phylogenetic perspectives in comparative biology would be enhanced by the development and refinement of minimal reporting standards for phylogenetic analyses. Encouraged by the development of the Minimum Information About a Microarray Experiment (MIAME) standard, we propose a similar roadmap for the development of a Minimal Information About a Phylogenetic Analysis (MIAPA) standard. Key in the successful development and implementation of such a standard will be broad participation by developers of phylogenetic analysis software, phylogenetic database developers, practitioners of phylogenomics, and journal editors. This paper is part of the special issue of OMICS on data standards.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63208/1/omi.2006.10.231.pd

Supine posture changes lung volumes and increases ventilation heterogeneity in cystic fibrosis

INTRODUCTION: Lung Clearance Index (LCI) is recognised as an early marker of cystic fibrosis (CF) lung disease. The effect of posture on LCI however is important when considering longitudinal measurements from infancy and when comparing LCI to imaging studies. METHODS: 35 children with CF and 28 healthy controls (HC) were assessed. Multiple breath washout (MBW) was performed both sitting and supine in triplicate and analysed for LCI, Scond, Sacin, and lung volumes. These values were also corrected for the Fowler dead-space to create 'alveolar' indices. RESULTS: From sitting to supine there was a significant increase in LCI and a significant decrease in FRC for both CF and HC (p<0.01). LCI, when adjusted to estimate 'alveolar' LCI (LCIalv), increased the magnitude of change with posture for both LCIalv and FRCalv in both groups, with a greater effect of change in lung volume in HC compared with children with CF. The % change in LCIalv for all subjects correlated significantly with lung volume % changes, most notably tidal volume/functional residual capacity (Vtalv/FRCalv (r = 0.54,p<0.001)). CONCLUSION: There is a significant increase in LCI from sitting to supine, which we believe to be in part due to changes in lung volume and also increasing ventilation heterogeneity related to posture. This may have implications in longitudinal measurements from infancy to older childhood and for studies comparing supine imaging methods to LCI

HDAC Inhibition Decreases the Expression of EGFR in Colorectal Cancer Cells

Epidermal growth factor receptor (EGFR), a receptor tyrosine kinase which promotes cell proliferation and survival, is abnormally overexpressed in numerous tumors of epithelial origin, including colorectal cancer (CRC). EGFR monoclonal antibodies have been shown to increase the median survival and are approved for the treatment of colorectal cancer. Histone deacetylases (HDACs), frequently overexpressed in colorectal cancer and several malignancies, are another attractive targets for cancer therapy. Several inhibitors of HDACs (HDACi) are developed and exhibit powerful antitumor abilities. In this study, human colorectal cancer cells treated with HDACi exhibited reduced EGFR expression, thereby disturbed EGF-induced ERK and Akt phosphorylation. HDACi also decreased the expression of SGLT1, an active glucose transporter found to be stabilized by EGFR, and suppressed the glucose uptake of cancer cells. HDACi suppressed the transcription of EGFR and class I HDACs were proved to be involved in this event. Chromatin immunoprecipitation analysis showed that HDACi caused the dissociation of SP1, HDAC3 and CBP from EGFR promoter. Our data suggested that HDACi could serve as a single agent to block both EGFR and HDAC, and may bring more benefits to the development of CRC therapy

Impact of abstinence and of reducing illicit drug use without abstinence on human immunodeficiency virus viral load

Background. Substance use is common among people living with human immunodeficiency virus (PLWH) and a barrier to achieving viral suppression. Among PLWH who report illicit drug use, we evaluated associations between HIV viral load (VL) and reduced use of illicit opioids, methamphetamine/crystal, cocaine/crack, and marijuana, regardless of whether or not abstinence was achieved. Methods. This was a longitudinal cohort study of PLWH from 7 HIV clinics or 4 clinical studies. We used joint longitudinal and survival models to examine the impact of decreasing drug use and of abstinence for each drug on viral suppression. We repeated analyses using linear mixed models to examine associations between change in frequency of drug use and VL. Results. The number of PLWH who were using each drug at baseline ranged from n = 568 (illicit opioids) to n = 4272 (marijuana). Abstinence was associated with higher odds of viral suppression (odds ratio [OR], 1.4-2.2) and lower relative VL (ranging from 21% to 42% by drug) for all 4 drug categories. Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with VL suppression (OR, 2.2, 1.6, respectively). Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with lower relative VL (47%, 38%, respectively). Conclusions. Abstinence was associated with viral suppression. In addition, reducing use of illicit opioids or methamphetamine/crystal, even without abstinence, was also associated with viral suppression. Our findings highlight the impact of reducing substance use, even when abstinence is not achieved, and the potential benefits of medications, behavioral interventions, and harm-reduction interventions

Thermodynamic Additivity of Sequence Variations: An Algorithm for Creating High Affinity Peptides Without Large Libraries or Structural Information

BACKGROUND: There is a significant need for affinity reagents with high target affinity/specificity that can be developed rapidly and inexpensively. Existing affinity reagent development approaches, including protein mutagenesis, directed evolution, and fragment-based design utilize large libraries and/or require structural information thereby adding time and expense. Until now, no systematic approach to affinity reagent development existed that could produce nanomolar affinity from small chemically synthesized peptide libraries without the aid of structural information. METHODOLOGY/PRINCIPAL FINDINGS: Based on the principle of additivity, we have developed an algorithm for generating high affinity peptide ligands. In this algorithm, point-variations in a lead sequence are screened and combined in a systematic manner to achieve additive binding energies. To demonstrate this approach, low-affinity lead peptides for multiple protein targets were identified from sparse random sequence space and optimized to high affinity in just two chemical steps. In one example, a TNF-α binding peptide with K(d) = 90 nM and high target specificity was generated. The changes in binding energy associated with each variation were generally additive upon combining variations, validating the basis of the algorithm. Interestingly, cooperativity between point-variations was not observed, and in a few specific cases, combinations were less than energetically additive. CONCLUSIONS/SIGNIFICANCE: By using this additivity algorithm, peptide ligands with high affinity for protein targets were generated. With this algorithm, one of the highest affinity TNF-α binding peptides reported to date was produced. Most importantly, high affinity was achieved from small, chemically-synthesized libraries without the need for structural information at any time during the process. This is significantly different than protein mutagenesis, directed evolution, or fragment-based design approaches, which rely on large libraries and/or structural guidance. With this algorithm, high affinity/specificity peptide ligands can be developed rapidly, inexpensively, and in an entirely chemical manner

Waveform Modelling for the Laser Interferometer Space Antenna

LISA, the Laser Interferometer Space Antenna, will usher in a new era in gravitational-wave astronomy. As the first anticipated space-based gravitational-wave detector, it will expand our view to the millihertz gravitational-wave sky, where a spectacular variety of interesting new sources abound: from millions of ultra-compact binaries in our Galaxy, to mergers of massive black holes at cosmological distances; from the beginnings of inspirals that will venture into the ground-based detectors' view to the death spiral of compact objects into massive black holes, and many sources in between. Central to realising LISA's discovery potential are waveform models, the theoretical and phenomenological predictions of the pattern of gravitational waves that these sources emit. This white paper is presented on behalf of the Waveform Working Group for the LISA Consortium. It provides a review of the current state of waveform models for LISA sources, and describes the significant challenges that must yet be overcome.Comment: 239 pages, 11 figures, white paper from the LISA Consortium Waveform Working Group, invited for submission to Living Reviews in Relativity, updated with comments from communit