Adaptive gain and filtering circuit for a sound reproduction system

Adaptive compressive gain and level dependent spectral shaping circuitry for a hearing aid include a microphone to produce an input signal and a plurality of channels connected to a common circuit output. Each channel has a preset frequency response. Each channel includes a filter with a preset frequency response to receive the input signal and to produce a filtered signal, a channel amplifier to amplify the filtered signal to produce a channel output signal, a threshold register to establish a channel threshold level, and a gain circuit. The gain circuit increases the gain of the channel amplifier when the channel output signal falls below the channel threshold level and decreases the gain of the channel amplifier when the channel output signal rises above the channel threshold level. A transducer produces sound in response to the signal passed by the common circuit output

Adaptive noise reduction circuit for a sound reproduction system

A noise reduction circuit for a hearing aid having an adaptive filter for producing a signal which estimates the noise components present in an input signal. The circuit includes a second filter for receiving the noise-estimating signal and modifying it as a function of a user's preference or as a function of an expected noise environment. The circuit also includes a gain control for adjusting the magnitude of the modified noise-estimating signal, thereby allowing for the adjustment of the magnitude of the circuit response. The circuit also includes a signal combiner for combining the input signal with the adjusted noise-estimating signal to produce a noise reduced output signal

Change Is in the Air: The Hypoxic Induction of Phenotype Switching in Melanoma

Melanoma cells can switch from a highly proliferative, less invasive state to a highly invasive, less proliferative state, a phenomenon termed phenotype switching. This results in a highly heterogenous tumor, where a slow-growing, aggressive population of cells may resist tumor therapy, and it predicts tumor recurrence. Here we discuss the observation made by Widmer et al. that hypoxia may drive phenotype switching

Electronic filters, hearing aids and methods

An electronic filter for an electroacoustic system. The system has a microphone for generating an electrical output from external sounds and an electrically driven transducer for emitting sound. Some of the sound emitted by the transducer returns to the microphone means to add a feedback contribution to its electical output. The electronic filter includes a first circuit for electronic processing of the electrical output of the microphone to produce a filtered signal. An adaptive filter, interconnected with the first circuit, performs electronic processing of the filtered signal to produce an adaptive output to the first circuit to substantially offset the feedback contribution in the electrical output of the microphone, and the adaptive filter includes means for adapting only in response to polarities of signals supplied to and from the first circuit. Other electronic filters for hearing aids, public address systems and other electroacoustic systems, as well as such systems, and methods of operating them are also disclosed

Sirolimus Enhances Cyclosporine A-Induced Cytotoxicity in Human Renal Glomerular Mesangial Cells

End Stage Renal Disease (ESRD) is an ever increasing problem worldwide. However the mechanisms underlying disease progression are not fully elucidated. This work addressed nephrotoxicity induced by the immunosuppressive agents' cyclosporine A (CsA) and sirolimus (SRL). Nephrotoxicity is the major limiting factor in long term use of CsA. SRL causes less nephrotoxicity than CsA. Therefore investigations into the differential effects of these agents may identify potential mechanisms of nephrotoxicity and means to prevent ESRD induced by therapeutic drugs. Using ELISA, Western blotting, quantitative PCR and a reporter gene assay we detailed the differential effects of CsA and SRL in human renal mesangial cells. CsA treatment increased profibrotic TGF-β1 secretion in human mesangial cells whereas SRL did not, indicating a role for TGF-β in CsA toxicity. However we observed a synergistic nephrotoxic effect when CsA and SRL were co-administered. These synergistic alterations may have been due to an increase in CTGF which was not evident when the immunosuppressive drugs were used alone. The CsA/SRL combination therapy significantly enhanced Smad signalling and altered the extracellular matrix regulator matrix metalloproteinase 9 (MMP-9). Inhibition of the ERK 1/2 pathway, attenuated these CsA/SRL induced alterations indicating a potentially significant role for this pathway

The Role of MAPK in Drug-Induced Kidney Injury

This paper focuses on the role that mitogen-activated protein kinases (MAPKs) play in drug-induced kidney injury. The MAPKs, of which there are four major classes (ERK, p38, JNK, and ERK5/BMK), are signalling cascades which have been found to be broadly conserved across a wide variety of organisms. MAPKs allow effective transmission of information from the cell surface to the cytosolic or nuclear compartments. Cross talk between the MAPKs themselves and with other signalling pathways allows the cell to modulate responses to a wide variety of external stimuli. The MAPKs have been shown to play key roles in both mediating and ameliorating cellular responses to stress including xenobiotic-induced toxicity. Therefore, this paper will discuss the specific role of the MAPKs in the kidney in response to injury by a variety of xenobiotics and the potential for therapeutic intervention at the level of MAPK signalling across different types of kidney disease

Compositional Proteomics: Effects of Spatial Constraints on Protein Quantification Utilizing Isobaric Tags.

Mass spectrometry (MS) has become an accessible tool for whole proteome quantitation with the ability to characterize protein expression across thousands of proteins within a single experiment. A subset of MS quantification methods (e.g., SILAC and label-free) monitor the relative intensity of intact peptides, where thousands of measurements can be made from a single mass spectrum. An alternative approach, isobaric labeling, enables precise quantification of multiple samples simultaneously through unique and sample specific mass reporter ions. Consequently, in a single scan, the quantitative signal comes from a limited number of spectral features (≤11). The signal observed for these features is constrained by automatic gain control, forcing codependence of concurrent signals. The study of constrained outcomes primarily belongs to the field of compositional data analysis. We show experimentally that isobaric tag proteomics data are inherently compositional and highlight the implications for data analysis and interpretation. We present a new statistical model and accompanying software that improves estimation accuracy and the ability to detect changes in protein abundance. Finally, we demonstrate a unique compositional effect on proteins with infinite changes. We conclude that many infinite changes will appear small and that the magnitude of these estimates is highly dependent on experimental design

Sloan Digital Sky Survey III Photometric Quasar Clustering: Probing the Initial Conditions of the Universe using the Largest Volume

The Sloan Digital Sky Survey has surveyed 14,555 square degrees of the sky, and delivered over a trillion pixels of imaging data. We present the large-scale clustering of 1.6 million quasars between z = 0.5 and z = 2.5 that have been classified from this imaging, representing the highest density of quasars ever studied for clustering measurements. This data set spans ~11,000 square degrees and probes a volume of 80(Gpc/h)^3. In principle, such a large volume and medium density of tracers should facilitate high-precision cosmological constraints. We measure the angular clustering of photometrically classified quasars using an optimal quadratic estimator in four redshift slices with an accuracy of ~25% over a bin width of l ~10 - 15 on scales corresponding to matter-radiation equality and larger (l ~ 2 - 30). Observational systematics can strongly bias clustering measurements on large scales, which can mimic cosmologically relevant signals such as deviations from Gaussianity in the spectrum of primordial perturbations. We account for systematics by employing a new method recently proposed by Agarwal et al. (2014) to the clustering of photometrically classified quasars. We carefully apply our methodology to mitigate known observational systematics and further remove angular bins that are contaminated by unknown systematics. Combining quasar data with the photometric luminous red galaxy (LRG) sample of Ross et al. (2011) and Ho et al. (2012), and marginalizing over all bias and shot noise-like parameters, we obtain a constraint on local primordial non-Gaussianity of fNL = -113+/-154 (1\sigma error). [Abridged]Comment: 35 pages, 15 figure

The Ultraviolet Imaging Telescope: Instrument and Data Characteristics

The Ultraviolet Imaging Telescope (UIT) was flown as part of the Astro observatory on the Space Shuttle Columbia in December 1990 and again on the Space Shuttle Endeavor in March 1995. Ultraviolet (1200-3300 Angstroms) images of a variety of astronomical objects, with a 40 arcmin field of view and a resolution of about 3 arcsec, were recorded on photographic film. The data recorded during the first flight are available to the astronomical community through the National Space Science Data Center (NSSDC); the data recorded during the second flight will soon be available as well. This paper discusses in detail the design, operation, data reduction, and calibration of UIT, providing the user of the data with information for understanding and using the data. It also provides guidelines for analyzing other astronomical imagery made with image intensifiers and photographic film.Comment: 44 pages, LaTeX, AAS preprint style and EPSF macros, accepted by PAS