A highly integrated 1.75-GHz 0.35-/spl mu/m CMOS transmitter is described. The I/Q modulator-based transmitter facilitates integration through the use of a unique mixer, termed a harmonic-rejection ...mixer, and a wide loop bandwidth phase-locked loop (PLL) for the RF synthesizer. The harmonic-rejection mixers are used to eliminate the need for a discrete IF filter and the use of a wide loop bandwidth PLL allowed for the complete integration of the synthesizers using low-Q components while achieving low phase noise. The entire transmit signal path from the digital-to-analog converters to the power amplifier, including two fully integrated frequency synthesizers, is integrated into a single-chip solution. The transmitter was tested with a testing buffer before the power amplifier (PA) and achieved less than 1.3/spl deg/ rms phase error when modulating a DCS-1800 GMSK signal. The prototype consumed 151 mA from a 3-V supply. A class-C PA, capable of driving 25 dBm off-chip, was included and the output was compared to the testing buffer with little change in the transmitter performance.
We consider the design of convolutional codes and low density parity check (LDPC) codes with minimum-shift keying (MSK) when the receiver employs iterative decoding and demodulation. The main idea ...proposed is the design of coded schemes that are well matched to the iterative decoding algorithm being used rather than to hypothetical maximum-likelihood decoding. We first show that the design is crucially dependent on whether the continuous phase encoder (CPE) is realized in recursive form or in nonrecursive form. We then consider the design of convolutionally coded systems and low density parity check codes with MSK to obtain near-capacity performance. With convolutional codes, we show that it is possible to improve the performance significantly by using a mixture of recursive and nonrecursive realizations for the CPE. For low density parity check codes, we show that codes designed for binary phase shift keying are optimal for MSK only if the nonrecursive realization is used; for the recursive realization, we design new LDPC codes based on the concept of density evolution. We show that these codes outperform the best known codes for MSK and have lower decoding complexity.
Abstract Apolipoprotein E was found to protect against the neurotoxic effects of a dimeric peptide derived from the receptor-binding region of this protein (residues 141–149). Both apoE3 and apoE4 ...conferred protection but the major N-terminal fragment of each isoform did not. Nor was significant protection provided by bovine serum albumin or apoA-I. Full-length apoE3 and apoE4 also inhibited the uptake of a fluorescent-labeled derivative of the peptide, suggesting that the mechanism of inhibition might involve competition for cell surface receptors/proteoglycans that mediate endocytosis and/or signaling pathways. These results might bear on the question of the role of apoE in neuronal degeneration, such as occurs in Alzheimer's disease where apoE4 confers a significantly greater risk of pathology.
Apolipoprotein (apo) E plays a major role in lipid metabolism by mediating cellular uptake of lipoprotein particles through interaction with members of the low density lipoprotein (LDL) receptor ...family. The primary region of apoE responsible for receptor binding has been limited to a cluster of basic amino acids between residues 134 and 150, located in the fourth helix of the N-terminal domain globular helix bundle structure. To investigate structural and functional requirements of this “receptor binding region” we engineered an apolipoprotein chimera wherein residues 131–151 of human apoE were substituted for residues 146–166 (helix 5) of Manduca sexta apolipophorin III (apoLp-III). Recombinant hybrid apolipoprotein was expressed in Escherichia coli, isolated, and characterized. Hybrid apolipoprotein and apoE3-N-terminal, but not apoLp-III, bound to heparin-Sepharose. Far UV circular dichroism spectroscopy revealed the presence of predominantly α-helix secondary structure, and stability studies revealed a urea denaturation midpoint of 1.05 m, similar to wild-type apoLp-III. Hybrid apolipoprotein-induced dimyristoylphosphatidylcholine (DMPC) bilayer vesicle solubilization activity was significantly enhanced compared with either parent protein, consistent with detection of solvent-exposed hydrophobic regions on the protein in fluorescent dye binding experiments. Unlike wild-type apoLp-III·DMPC complexes, disc particles bearing the hybrid apolipoprotein competed with 125ILDL for binding to the LDL receptor on cultured human skin fibroblasts. We conclude that a hybrid apolipoprotein containing a key receptor recognition element of apoE preserves the structural integrity of the parent protein while conferring a new biological activity, illustrating the potential of helix swapping to introduce desirable biological properties into unrelated or engineered apolipoproteins.
A 1.75 GHz highly-integrated narrow-band complementary metal oxide semiconductors (CMOS) transmitter was proposed with harmonic-rejection mixers. The proposed architecture consists of two baseband ...signal paths, an image/harmonic rejection upconversion mixer, a channel-selection sysnthesiser, a fixed-frequency Rf synthesizer and two quadrature generation circuits. A prototype device based on the harmonic-rejection CMOS integrated circuit concept was fabricated in a 0.35 mu m, double-poly, 5-layer metal CMOS process. A breakdown of the power consumption and a summary of test results were described.
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Carbon-11 labeled SL25.1188 is a promising reversible monoamine oxidase-B (MAO-B) radioligand that was recently translated for human positron emission tomography (PET) imaging. ...Herein, we report the development of a novel fluorinated derivative, namely, 18F(S)-3-(6-(3-fluoropropoxy)benzodisoxazol-3-yl)-5-(methoxymethyl)oxazolidin-2-one (18FFSL25.1188; 18F6), as a candidate 18F-labeled MAO-B radioligand, and, its subsequent preclinical evaluation in non-human primates (NHP). 18F6 was produced and isolated (>6 GBq) with high radiochemical purity (>99%), and molar activity (>100 GBq/µmol at time of injection). Autoradiography studies conducted in post-mortem human brain sections revealed 18F6 binding in MAO-B rich regions. PET imaging study of 18F6 in NHP showed high brain uptake (SUV > 2.5) as well as a regional brain radioactivity distribution in accordance with MAO-B expression. 18F6 displayed favorable in vivo kinetics, with an early peak in the time-activity curve followed by progressive wash-out from the NHP brain. Specificity of 18F6 was investigated in a pre-treatment study with l-deprenyl (1.0 mg/kg) wherein reduced radioligand uptake was observed in all MAO-B rich regions. Results from the current preclinical investigation suggests 18F6 is a promising MAO-B PET radioligand. Further evaluation of 18F6 and structurally related 18F-analogs are underway to identify an optimized candidate for clinical research studies.
PURPOSEWhile there is strong evidence supporting the importance of telemedicine in stroke, its role in other areas of neurology is not as clear. The goal of this review is to provide an overview of ...evidence-based data on the role of teleneurology in the care of patients with neurologic disorders other than stroke.
RECENT FINDINGSStudies across multiple specialties report noninferiority of evaluations by telemedicine compared with traditional, in-person evaluations in terms of patient and caregiver satisfaction. Evidence reports benefits in expediting care, increasing access, reducing cost, and improving diagnostic accuracy and health outcomes. However, many studies are limited, and gaps in knowledge remain.
SUMMARYTelemedicine use is expanding across the vast array of neurologic disorders. More studies are needed to validate and support its use.
In this Viewpoint, we highlight the history of positron emission tomography (PET) radiotracer development to quantify changes in monoamine oxidase (MAO)-A and -B enzyme expression or activity. MAO-A ...and MAO-B are critical for understanding monoaminergic pathways in psychiatric addiction disorders, and more recently in neurodegenerative disorders with MAO-B expression in astrogliosis. Unique radiochemical innovations have been shown for neuroimaging of MAOs including the clinical translation of irreversible propargylamine-based suicide inhibitors, application of deuterium-substitution to slow down metabolism, development of trapped metabolite imaging agents, and unique 11C-carbonylation chemistry toward novel high-affinity reversibly binding inhibitors.
The N‐terminal domain of human apolipoprotein E (apoE‐NT) harbors residues critical for interaction with members of the low‐density lipoprotein receptor (LDLR) family. Whereas lipid free apoE‐NT ...adopts a stable four‐helix bundle conformation, a lipid binding induced conformational adaptation is required for manifestation of LDLR binding ability. To investigate the structural basis for this conformational change, the short helix connecting helix 1 and 2 in the four‐helix bundle was replaced by the sequence NPNG, introducing a β‐turn. Recombinant helix‐to‐turn (HT) variant apoE3‐NT was produced in Escherichia coli, isolated and characterized. Stability studies revealed a denaturation transition midpoint of 1.9 m guanidine hydrochloride for HT apoE3‐NT vs. 2.5 m for wild‐type apoE3‐NT. Wild‐type and HT apoE3‐NT form dimers in solution via an intermolecular disulfide bond. Native PAGE showed that reconstituted high‐density lipoprotein prepared with HT apoE3‐NT have a diameter in the range of 9 nm and possess binding activity for the LDLR on cultured human skin fibroblasts. In phospholipid vesicle solubilization assays, HT apoE3‐NT was more effective than wild‐type apoE3‐NT at inducing a time dependent decrease in dimyristoylphosphatidylglycerol vesicle light scattering intensity. In lipoprotein binding assays, HT apoE3‐NT protected human low‐density lipoprotein from phospholipase C induced aggregation to a greater extent that wild‐type apoE3‐NT. The results indicate that a mutation at one end of the apoE3‐NT four‐helix bundle markedly enhances the lipid binding activity of this protein. In the context of lipoprotein associated full‐length apoE, increased lipid binding affinity of the N‐terminal domain may alter the balance between receptor‐active and ‐inactive conformational states.
Parametric interpolation has many advantages over linear interpolation in machining curves. Real time parametric interpolation research so far has addressed achieving a uniform feed rate, confined ...chord errors and jerk limited trajectory planning. However, simultaneous consideration of confined chord errors that respect the acceleration and deceleration capabilities of the machine has not been attempted. In this paper, the offline detection of feed rate sensitive corners is proposed. The velocity profile in these zones is planned so that chord errors are satisfied while simultaneously accommodating the machine's acceleration and deceleration limits. Outside the zone of the feed rate sensitive corners, the feed rate is planned using the Taylor approximation. Simulation results indicate that the offline detection of feed rate sensitive corners improves parametric interpolation. For real time interpolation, the parametric curve information can be augmented with the detected feed rate sensitive corners that are stored in 2×2 matrices.
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