White-nose syndrome initiates a cascade of physiologic disturbances in the hibernating bat host

Acknowledgments This project was financially supported by the US Geological Survey through a cooperative agreement with the University of Wisconsin – Madison. We are indebted to Dave and Jennifer Redell and Paul White from the Wisconsin Department of Natural Resources for collecting the animals used to complete this study and for assisting with data collection. We thank Melissa Behr for assistance with necropsies and NWHC Animal Care Staff for their help with set-up and maintenance of animals. We thank Lobke Vaanholt and Catherine Hambly (University of Aberdeen, Scotland) for their expertise and coordination in the analyses of the DLW blood samples. Funds were used for direct project costs only. Use of trade, product, or firm names is for descriptive purposes only and does not imply endorsement by the US Government.

Development and regeneration of neuronal circuits in the vertebrate retina

Thesis (Ph.D.)--University of Washington, 2016-08

An identification procedure of multi-input Wiener models for the distortion analysis of nonlinear circuits

In this contribution, a system identification procedure of a two-input Wiener model suitable for the analysis of the disturbance behavior of integrated nonlinear circuits is presented. The identified block model is comprised of two linear dynamic and one static nonlinear block, which are determined using an parameterized approach. In order to characterize the linear blocks, an correlation analysis using a white noise input in combination with a model reduction scheme is adopted. After having characterized the linear blocks, from the output spectrum under single tone excitation at each input a linear set of equations will be set up, whose solution gives the coefficients of the nonlinear block. By this data based black box approach, the distortion behavior of a nonlinear circuit under the influence of an interfering signal at an arbitrary input port can be determined. Such an interfering signal can be, for example, an electromagnetic interference signal which conductively couples into the port of consideration. © 2011 Author(s).

A Study of the Robustness Against SEUs of Digital Circuits Implemented with FPGA DSPs

In this paper we present an experimental validation of the reliability increase of digital circuits implemented in XilinxTMFPGAs when they are implemented using the DSPs (Digital Signal Processors) that are available in the reconfigurable device. For this purpose, we have used a fault-injection platform developed by our research group, NESSY [1]. The presented experiments demonstrate that the probability of occurrence of a SEU effect is similar both in the circuits implemented with and without using embedded DSPs. However, the former are more efficient in terms of area usage, which leads to a decrease in the probability of a SEU occurrence.

Synchronization of Heteroclinic Circuits Through Learning in Chains of Neural Motifs

The synchronization of oscillatory activity in networks of neural networks is usually implemented through coupling the state variables describing neuronal dynamics. In this study we discuss another but complementary mechanism based on a learning process with memory. A driver network motif, acting as a teacher, exhibits winner-less competition (WLC) dynamics, while a driven motif, a learner, tunes its internal couplings according to the oscillations observed in the teacher. We show that under appropriate training the learner motif can dynamically copy the coupling pattern of the teacher and thus synchronize oscillations with the teacher. Then, we demonstrate that the replication of the WLC dynamics occurs for intermediate memory lengths only. In a unidirectional chain of N motifs coupled through teacher-learner paradigm the time interval required for pattern replication grows linearly with the chain size, hence the learning process does not blow up and at the end we observe phase synchronized oscillations along the chain. We also show that in a learning chain closed into a ring the network motifs come to a consensus, i.e. to a state with the same connectivity pattern corresponding to the mean initial pattern averaged over all network motifs.

Electrical characterization of electronic circuits produced by inkjet printing

Dissertação de Mestrado, Engenharia Electrónica e Telecomunicações, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014

Corona Discharge Model for Transmission Lines by Lumped Elements

This paper shows the insertion of corona effect in a transmission line model based on lumped elements. The development is performed considering a frequency-dependent line representation by cascade of pi sections and state equations. Hence, the detailed profile of currents and voltages along the line, described from a non-homogeneous system of differential equations, can be obtained directly in time domain applying numerical or analytic solution integration methods. The corona discharge model is also based on lumped elements and is implemented from the well-know Skilling-Umoto Model.

Applying a new methodology to verify transmission line model performance - the equivalent impedance test

The objective of this paper is to present a methodology to analyze a transmission line model used in electromagnetic transitory simulators, called equivalent impedance test. Initially the definition of equivalent impedance reference test is shown. Soon after this methodology is applied to a transmission line model, the Quasi-Modes model. The studies were accomplished in a hypothetical non-transposed three-phase transmission fine of 440 kV. The line length is 500 km, and it was modeled through cascades of pi-circuits (with 50 pi's circuits, each with 10 km length).

Rational design of a bacterial transcriptional cascade for amplifying gene expression capacity

Cascade regulatory circuits have been described that control numerous cell processes, and may provide models for the design of artificial circuits with novel properties. Here we describe the design of a transcriptional regulatory cascade to amplify the cell response to a given signal. We used the salicylate-responsive activators of Pseudomonas putida NahR of the naphthalene degradation plasmid NAH7 and XylS2, a mutant regulator of the TOL plasmid for catabolism of m-xylene and their respective cognate promoters Psal and Pm. Control of the expression of xylS2 with the nahR/Psal system permitted either their selective activation with specific effectors for each protein or the simultaneous activation of both of them with salicylate. When cells face the common effector of the two regulators, both the increase in XylS2 concentration and the stimulation of its activity act synergistically on the Pm promoter, amplifying the gene expression capacity by at least one order of magnitude with respect to the individual systems. By changing the hierarchy of regulators, we showed that the specific features of the downstream regulator were crucial for the amplification effect. Directed changes in the effector profile of the regulators allowed the extension of the amplifying system to other molecular signals.

Blockade of vascular smooth muscle cell proliferation and intimal thickening after balloon injury by the sulfated oligosaccharide PI-88: Phosphomannopentaose sulfate directly binds FGF-2, blocks cellular signaling, and inhibits proliferation

Percutaneous transluminal coronary angioplasty is a frequently used interventional technique to reopen arteries that have narrowed because of atherosclerosis. Restenosis, or renarrowing of the artery shortly after angioplasty, is a major limitation to the success of the procedure and is due mainly to smooth muscle cell accumulation in the artery wall at the site of balloon injury. In the present study, we demonstrate that the antiangiogenic sulfated oligosaccharide, PI-88, inhibits primary vascular smooth muscle cell proliferation and reduces intimal thickening 14 days after balloon angioplasty of rat and rabbit arteries. PI-88 reduced heparan sulfate content in the injured artery wall and prevented change in smooth muscle phenotype. However, the mechanism of PI-88 inhibition was not merely confined to the antiheparanase activity of this compound. PI-88 blocked extracellular signal-regulated kinase-1/2 (ERK1/2) activity within minutes of smooth muscle cell injury. It facilitated FGF-2 release from uninjured smooth muscle cells in vitro, and super-released FGF-2 after injury while inhibiting ERK1/2 activation. PI-88 inhibited the decrease in levels of FGF-2 protein in the rat artery wall within 8 minutes of injury. PI-88 also blocked injury-inducible ERK phosphorylation, without altering the clotting time in these animals. Optical biosensor studies revealed that PI-88 potently inhibited (K-i 10.3 nmol/L) the interaction of FGF-2 with heparan sulfate. These findings show for the first time the capacity of this sulfated oligosaccharide to directly bind FGF-2, block cellular signaling and proliferation in vitro, and inhibit injury-induced smooth muscle cell hyperplasia in two animal models. As such, this study demonstrates a new role for PI-88 as an inhibitor of intimal thickening after balloon angioplasty. The full text of this article is available online at http://www.circresaha.org.

Role of Phosphorylation of the Oxysterol Binding Protein (OSBP) in (PI(4)P) and Sterol-Containing Membrane Recognition and Binding

Studies have demonstrated that the oxysterol binding protein (OSBP) acts as a phosphatidylinositol phosphate (PIP)-sterol exchanger at membrane contact sites (MCS) of the endoplasmic reticulum (ER) and Golgi. OSBP is known to pick up phosphatidylinositol-4-phosphate (PI(4)P) from the ER, transfer it to the trans-Golgi in exchange for a cholesterol molecule that is then transferred from the trans-Golgi to the ER. Upon further examination of this pathway by Ridgway et al. (1), it appeared that phosphorylation of OSBP played a role in the localization of OSBP. The dephosphorylation state of OSBP was linked to Golgi localization and the depletion of cholesterol at the ER. To mimic the phosphorylated state of OSBP, the mutant OSBP-S5E was designed by Ridgway et al. (1). The lipid and sterol recognition by wt-OSBP and its phosphomimic mutant OSBP-S5E were investigated using immobilized lipid bilayers and dual polarization interferometry (DPI). DPI is a technique in which the protein binding affinity to immobilized lipid bilayers is measured and the binding behavior is examined through real time. Lipid bilayers containing 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and varying concentrations of PI(4)Ps or sterols (cholesterol or 25-hydroxycholesterol) were immobilized on a silicon nitride chip. It was determined that wt-OSBP binds differently to PI(4)P-containing bilayers compared to OSBP-S5E. The binding behavior suggested that wt-OSBP extracts PI(4)P and the change in the binding behavior, in the case of OSBP-S5E, suggested that the phosphorylation of OSBP may prevent the recognition and/or extraction of PI(4)P. In the presence of sterols, the overall binding behavior of OSBP, regardless of phosphorylation state, was fairly similar. The maximum specific bound mass of OSBP to sterols did not differ as the concentration of sterols increased. However, comparing the maximum specific bound mass of OSBP to cholesterol with oxysterol (25-hydroxycholesterol), OSBP displayed nearly a 2-fold increase in bound mass. With the absence of the wt-OSBP-PI(4)P binding behavior, it can be speculated that the sterols were not extracted. In addition, the binding behavior of OSBP was further tested using a fluorescence based binding assay. Using 22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol (22-NBD cholesterol), wt-OSBP a one site binding dissociation constant Kd, of 15 ± 1.4 nM was determined. OSBP-S5E did not bind to 22-NBD cholesterol and Kd value was not obtained.

Polyphase Implementation of Non-recursive Comb Decimators for Sigma-Delta A/D Converters

In a sigma-delta analog to digital (A/D) As most of the sigma-delta ADC applications require converter, the most computationally intensive block is decimation filters with linear phase characteristics, the decimation filter and its hardware implementation symmetric Finite Impulse Response (FIR) filters are may require millions of transistors. Since these widely used for implementation. But the number of FIR converters are now targeted for a portable application, filter coefficients will be quite large for implementing a a hardware efficient design is an implicit requirement. narrow band decimation filter. Implementing decimation In this effect, this paper presents a computationally filter in several stages reduces the total number of filter efficient polyphase implementation of non-recursive coefficients, and hence reduces the hardware complexity cascaded integrator comb (CIC) decimators for and power consumption [2]. Sigma-Delta Converters (SDCs). The SDCs are The first stage of decimation filter can be operating at high oversampling frequencies and hence implemented very efficiently using a cascade of integrators require large sampling rate conversions. The filtering and comb filters which do not require multiplication or and rate reduction are performed in several stages to coefficient storage. The remaining filtering is performed reduce hardware complexity and power dissipation. either in single stage or in two stages with more complex The CIC filters are widely adopted as the first stage of FIR or infinite impulse response (IIR) filters according to decimation due to its multiplier free structure. In this the requirements. The amount of passband aliasing or research, the performance of polyphase structure is imaging error can be brought within prescribed bounds by compared with the CICs using recursive and increasing the number of stages in the CIC filter. The non-recursive algorithms in terms of power, speed and width of the passband and the frequency characteristics area. This polyphase implementation offers high speed outside the passband are severely limited. So, CIC filters operation and low power consumption. The polyphase are used to make the transition between high and low implementation of 4th order CIC filter with a sampling rates. Conventional filters operating at low decimation factor of '64' and input word length of sampling rate are used to attain the required transition '4-bits' offers about 70% and 37% of power saving bandwidth and stopband attenuation. compared to the corresponding recursive and Several papers are available in literature that deals non-recursive implementations respectively. The same with different implementations of decimation filter polyphase CIC filter can operate about 7 times faster architecture for sigma-delta ADCs. Hogenauer has than the recursive and about 3.7 times faster than the described the design procedures for decimation and non-recursive CIC filters.

Remarks concerning the double cascade as a necessary mechanism for the instability of steady equivalent-barotropic flows

n a recent paper, Petroniet al. claim that a necessary condition for the instability of two-dimensional steady flows is a «double cascade» of energy and enstrophy respectively to larger and to smaller scales of motion. It is shown here that the analytical reasoning employed by Petroniet al. is flawed and that their conclusions are incorrect. What is true is that in any scale interaction (whether an instability or not), neither energy nor enstrophy can be transferred in one spectral direction only, but this result is extremely well known.

Mixed-signal analog-digital circuits design on the pre-diffused digital array using trapezoidal association of transistors

The mixed-signal and analog design on a pre-diffused array is a challenging task, given that the digital array is a linear matrix arrangement of minimum-length transistors. To surmount this drawback a specific discipline for designing analog circuits over such array is required. An important novel technique proposed is the use of TAT (Trapezoidal Associations of Transistors) composite transistors on the semi-custom Sea-Of-Transistors (SOT) array. The analysis and advantages of TAT arrangement are extensively analyzed and demonstrated, with simulation and measurement comparisons to equivalent single transistors. Basic analog cells were also designed as well in full-custom and TAT versions in 1.0mm and 0.5mm digital CMOS technologies. Most of the circuits were prototyped in full-custom and TAT-based on pre-diffused SOT arrays. An innovative demonstration of the TAT technique is shown with the design and implementation of a mixed-signal analog system, i. e., a fully differential 2nd order Sigma-Delta Analog-to-Digital (A/D) modulator, fabricated in both full-custom and SOT array methodologies in 0.5mm CMOS technology from MOSIS foundry. Three test-chips were designed and fabricated in 0.5mm. Two of them are IC chips containing the full-custom and SOT array versions of a 2nd-Order Sigma-Delta A/D modulator. The third IC contains a transistors-structure (TAT and single) and analog cells placed side-by-side, block components (Comparator and Folded-cascode OTA) of the Sigma-Delta modulator.

Automatic layout generation of static CMOS circuits targeting delay and power

The evolution of integrated circuits technologies demands the development of new CAD tools. The traditional development of digital circuits at physical level is based in library of cells. These libraries of cells offer certain predictability of the electrical behavior of the design due to the previous characterization of the cells. Besides, different versions of each cell are required in such a way that delay and power consumption characteristics are taken into account, increasing the number of cells in a library. The automatic full custom layout generation is an alternative each time more important to cell based generation approaches. This strategy implements transistors and connections according patterns defined by algorithms. So, it is possible to implement any logic function avoiding the limitations of the library of cells. Tools of analysis and estimate must offer the predictability in automatic full custom layouts. These tools must be able to work with layout estimates and to generate information related to delay, power consumption and area occupation. This work includes the research of new methods of physical synthesis and the implementation of an automatic layout generation in which the cells are generated at the moment of the layout synthesis. The research investigates different strategies of elements disposition (transistors, contacts and connections) in a layout and their effects in the area occupation and circuit delay. The presented layout strategy applies delay optimization by the integration with a gate sizing technique. This is performed in such a way the folding method allows individual discrete sizing to transistors. The main characteristics of the proposed strategy are: power supply lines between rows, over the layout routing (channel routing is not used), circuit routing performed before layout generation and layout generation targeting delay reduction by the application of the sizing technique. The possibility to implement any logic function, without restrictions imposed by a library of cells, allows the circuit synthesis with optimization in the number of the transistors. This reduction in the number of transistors decreases the delay and power consumption, mainly the static power consumption in submicrometer circuits. Comparisons between the proposed strategy and other well-known methods are presented in such a way the proposed method is validated.