A high-performance microflowmeter with built-in self test

This paper reports the development of a high-performance readout scheme based on a switched-capacitor circuit and intended for use with an ultrasensitive microflowmeter. The microflow transducer improves significantly on the resolution of current flow devices and uses a differential capacitive pressure sensor to measure the flow. The readout electronics feature a clocking speed of 100 kHz and can drive loads as high as 35 pF. The high d.c. gain of the circuit topology (75 dB) is relatively insensitive to stray input capacitance and is ideally suited for a multichip sensor realization. The uncompensated linearity of the overall readout circuit is 10 bits and the pressure/flow resolution is 12 bits. Since ultrasensitive membranes respond to electrostatic forces, the output is characterized as a function of the duty cycle and pulse width of the readout clocking waveforms. The membrane does not respond to these waveforms for high frequencies ( > 50 kHz), but for lower frequencies the diaphragm deflects in response to the time-average voltage applied across the device. A self-test mode can therefore be implemented simply by changing the duty cycle of this pulse. By modifying the amplitude of the waveform, the device can be autocalibrated over a limited pressure range. The transducer and circuitry have been integrated into a flow package, and the multichip device has been tested versus a calibrated gas flow.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30918/1/0000588.pd

A short hairpin RNA screen of interferon-stimulated genes identifies a novel negative regulator of the cellular antiviral response

ABSTRACT The type I interferon (IFN) signaling pathway restricts infection of many divergent families of RNA and DNA viruses by inducing hundreds of IFN-stimulated genes (ISGs), some of which have direct antiviral activity. We screened 813 short hairpin RNA (shRNA) constructs targeting 245 human ISGs using a flow cytometry approach to identify genes that modulated infection of West Nile virus (WNV) in IFN-β-treated human cells. Thirty ISGs with inhibitory effects against WNV were identified, including several novel genes that had antiviral activity against related and unrelated positive-strand RNA viruses. We also defined one ISG, activating signal cointegrator complex 3 (ASCC3), which functioned as a negative regulator of the host defense response. Silencing of ASCC3 resulted in upregulation of multiple antiviral ISGs, which correlated with inhibition of infection of several positive-strand RNA viruses. Reciprocally, ectopic expression of human ASCC3 or mouse Ascc3 resulted in downregulation of ISGs and increased viral infection. Mechanism-of-action and RNA sequencing studies revealed that ASCC3 functions to modulate ISG expression in an IRF-3- and IRF-7-dependent manner. Compared to prior ectopic ISG expression studies, our shRNA screen identified novel ISGs that restrict infection of WNV and other viruses and defined a new counterregulatory ISG, ASCC3, which tempers cell-intrinsic immunity. IMPORTANCE West Nile virus (WNV) is a mosquito-transmitted virus that continues to pose a threat to public health. Innate immune responses, especially those downstream of type I interferon (IFN) signaling, are critical for controlling virus infection and spread. We performed a genetic screen using a gene silencing approach and identified 30 interferon-stimulated genes (ISGs) that contributed to the host antiviral response against WNV. As part of this screen, we also identified a novel negative regulatory protein, ASCC3, which dampens expression of ISGs, including those with antiviral or proinflammatory activity. In summary, our studies define a series of heretofore-uncharacterized ISGs with antiviral effects against multiple viruses or counterregulatory effects that temper IFN signaling and likely minimize immune-mediated pathology

GPU-based Iterative Cone Beam CT Reconstruction Using Tight Frame Regularization

X-ray imaging dose from serial cone-beam CT (CBCT) scans raises a clinical concern in most image guided radiation therapy procedures. It is the goal of this paper to develop a fast GPU-based algorithm to reconstruct high quality CBCT images from undersampled and noisy projection data so as to lower the imaging dose. For this purpose, we have developed an iterative tight frame (TF) based CBCT reconstruction algorithm. A condition that a real CBCT image has a sparse representation under a TF basis is imposed in the iteration process as regularization to the solution. To speed up the computation, a multi-grid method is employed. Our GPU implementation has achieved high computational efficiency and a CBCT image of resolution 512\times512\times70 can be reconstructed in ~5 min. We have tested our algorithm on a digital NCAT phantom and a physical Catphan phantom. It is found that our TF-based algorithm is able to reconstrct CBCT in the context of undersampling and low mAs levels. We have also quantitatively analyzed the reconstructed CBCT image quality in terms of modulation-transfer-function and contrast-to-noise ratio under various scanning conditions. The results confirm the high CBCT image quality obtained from our TF algorithm. Moreover, our algorithm has also been validated in a real clinical context using a head-and-neck patient case. Comparisons of the developed TF algorithm and the current state-of-the-art TV algorithm have also been made in various cases studied in terms of reconstructed image quality and computation efficiency.Comment: 24 pages, 8 figures, accepted by Phys. Med. Bio

Results from the Atacama B-mode Search (ABS) Experiment

The Atacama B-mode Search (ABS) is an experiment designed to measure cosmic microwave background (CMB) polarization at large angular scales ($\ell>40$). It operated from the ACT site at 5190~m elevation in northern Chile at 145 GHz with a net sensitivity (NEQ) of 41 $\mu$K$\sqrt{\rm s}$. It employed an ambient-temperature sapphire half-wave plate rotating at 2.55 Hz to modulate the incident polarization signal and reduce systematic effects. We report here on the analysis of data from a 2400 deg$^2$ patch of sky centered at declination $-42^\circ$ and right ascension $25^\circ$. We perform a blind analysis. After unblinding, we find agreement with the Planck TE and EE measurements on the same region of sky. We marginally detect polarized dust emission and give an upper limit on the tensor-to-scalar ratio of $r<2.3$ (95% cl) with the equivalent of 100 on-sky days of observation. We also present a new measurement of the polarization of Tau A and introduce new methods associated with HWP-based observations.Comment: 38 pages, 11 figure

Delta-Aminolevulinic Acid-Mediated Photodiagnoses in Surgical Oncology: A Historical Review of Clinical Trials.

Fluorescence imaging is an emerging clinical technique for real-time intraoperative visualization of tumors and their boundaries. Though multiple fluorescent contrast agents are available in the basic sciences, few fluorescence agents are available for clinical use. Of the clinical fluorophores, delta aminolevulinic acid (5ALA) is unique for generating visible wavelength tumor-specific fluorescence. In 2017, 5ALA was FDA-approved for glioma surgery in the United States. Additionally, clinical studies suggest this agent may have utility in surgical subspecialties outside of neurosurgery. Data from dermatology, OB/GYN, urology, cardiothoracic surgery, and gastrointestinal surgery show 5ALA is helpful for intraoperative visualization of malignant tissues in multiple organ systems. This review summarizes data from English-language 5ALA clinical trials across surgical subspecialties. Imaging systems, routes of administration, dosing, efficacy, and related side effects are reviewed. We found that modified surgical microscopes and endoscopes are the preferred imaging devices. Systemic dosing across surgical specialties range between 5 and 30 mg/kg bodyweight. Multiple studies discussed potential for skin irritation with sun exposure, however this side effect is infrequently reported. Overall, 5ALA has shown high sensitivity for labeling malignant tissues and providing a means to visualize malignant tissue not apparent with standard operative light sources

The Atacama Cosmology Telescope: Two-Season ACTPol Spectra and Parameters

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg$^2$ of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with Planck and WMAP data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the LCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. Adding the new data to planck temperature data tightens the limits on damping tail parameters, for example reducing the joint uncertainty on the number of neutrino species and the primordial helium fraction by 20%.Comment: 23 pages, 25 figure

Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators

The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across eight mammals to identify biases in gene content and the selective pressures that preserved the surviving ancestral genes. Our findings indicate that survival was nonrandom, and in two cases, convergent across placental and marsupial mammals. We conclude that the gene content of the Y chromosome became specialized through selection to maintain the ancestral dosage of homologous X-Y gene pairs that function as broadly expressed regulators of transcription, translation and protein stability. We propose that beyond its roles in testis determination and spermatogenesis, the Y chromosome is essential for male viability, and has unappreciated roles in Turner (tm) s syndrome and in phenotypic differences between the sexes in health and disease

Cross-National Differences in Victimization : Disentangling the Impact of Composition and Context

Varying rates of criminal victimization across countries are assumed to be the outcome of countrylevel structural constraints that determine the supply ofmotivated o¡enders, as well as the differential composition within countries of suitable targets and capable guardianship. However, previous empirical tests of these ‘compositional’ and ‘contextual’ explanations of cross-national di¡erences have been performed upon macro-level crime data due to the unavailability of comparable individual-level data across countries. This limitation has had two important consequences for cross-national crime research. First, micro-/meso-level mechanisms underlying cross-national differences cannot be truly inferred from macro-level data. Secondly, the e¡ects of contextual measures (e.g. income inequality) on crime are uncontrolled for compositional heterogeneity. In this paper, these limitations are overcome by analysing individual-level victimization data across 18 countries from the International CrimeVictims Survey. Results from multi-level analyses on theft and violent victimization indicate that the national level of income inequality is positively related to risk, independent of compositional (i.e. micro- and meso-level) di¡erences. Furthermore, crossnational variation in victimization rates is not only shaped by di¡erences in national context, but also by varying composition. More speci¢cally, countries had higher crime rates the more they consisted of urban residents and regions with lowaverage social cohesion.