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ABSTRACT: Two cationic, amphipathic peptoids (poly-N-substituted glycines) were developed as new molecular transporters, which have extensive cellullar uptake and utilize different internalization mechanisms from purely cationic polyguanidine comparators.
Molecular BioSystems 07/2012; 8(10):2626-8. · 3.53 Impact Factor
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ABSTRACT: Adaptive antenna array processing is widely known to provide significant anti-interference capabilities within a Global Navigation Satellite Systems (GNSS) receiver. A main challenge in the quest for such receiver architecture has always been the computational/processing requirements. Even more demanding would be to try and incorporate the flexibility of the Software-Defined Radio (SDR) design philosophy in such an implementation. This paper documents a feasible approach to a real-time SDR implementation of a beam-steered GNSS receiver and validates its performance. This research implements a real-time software receiver on a widely-available x86-based multi-core microprocessor to process four-element antenna array data streams sampled with 16-bit resolution. The software receiver is capable of 12 channels all-in-view Controlled Reception Pattern Antenna (CRPA) array processing capable of rejecting multiple interferers. Single Instruction Multiple Data (SIMD) instructions assembly coding and multithreaded programming, the key to such an implementation to reduce computational complexity, are fully documented within the paper. In conventional antenna array systems, receivers use the geometry of antennas and cable lengths known in advance. The documented CRPA implementation is architected to operate without extensive set-up and pre-calibration and leverages Space-Time Adaptive Processing (STAP) to provide adaptation in both the frequency and space domains. The validation component of the paper demonstrates that the developed software receiver operates in real time with live Global Positioning System (GPS) and Wide Area Augmentation System (WAAS) L1 C/A code signal. Further, interference rejection capabilities of the implementation are also demonstrated using multiple synthetic interferers which are added to the live data stream.
Sensors 01/2012; 12(10):13417-40. · 1.74 Impact Factor
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ABSTRACT: Due to their weak received signal power, Global Positioning System (GPS) signals are vulnerable to radio frequency interference. Adaptive beam and null steering of the gain pattern of a GPS antenna array can significantly increase the resistance of GPS sensors to signal interference and jamming. Since adaptive array processing requires intensive computational power, beamsteering GPS receivers were usually implemented using hardware such as field-programmable gate arrays (FPGAs). However, a software implementation using general-purpose processors is much more desirable because of its flexibility and cost effectiveness. This paper presents a GPS software-defined radio (SDR) with adaptive beamsteering capability for anti-jam applications. The GPS SDR design is based on an optimized desktop parallel processing architecture using a quad-core Central Processing Unit (CPU) coupled with a new generation Graphics Processing Unit (GPU) having massively parallel processors. This GPS SDR demonstrates sufficient computational capability to support a four-element antenna array and future GPS L5 signal processing in real time. After providing the details of our design and optimization schemes for future GPU-based GPS SDR developments, the jamming resistance of our GPS SDR under synthetic wideband jamming is presented. Since the GPS SDR uses commercial-off-the-shelf hardware and processors, it can be easily adopted in civil GPS applications requiring anti-jam capabilities.
Sensors 01/2011; 11(9):8966-91. · 1.74 Impact Factor
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ABSTRACT: Deep and frequent Global Positioning System (GPS) signal fading due to strong ionospheric scintillation is a major concern for GPS-guided aviation in equatorial areas during high solar activity. A GPS aviation receiver may lose carrier tracking lock under deep fading, and a lost channel cannot be used for position calculation until lock is reestablished. Hence, frequent loss of lock due to frequent fading can significantly reduce the availability of GPS aviation. However, the geometric diversity of the satellites can mitigate scintillation impact on GPS aviation depending on the correlation level of deep fades between satellites. This paper proposes a metric to measure the correlation level of two fading channels from the perspective of GPS aviation. Using this metric, the satellite-to-satellite correlation is studied based on real scintillation data. The low satellite-to-satellite correlation shown in this paper envisions notable availability ben-efit from the geometric diversity of satellites under strong scintillation. In addition, this paper proposes a way to generate correlated fad-ing processes with arbitrary correlation coefficients. Using this correlated fading process model, the availability of Localizer Performance with Vertical guidance (LPV)-200 under severe scintillation scenarios is analyzed. The result emphasizes the importance of a fast reac-quisition capability of an aviation receiver after a brief outage, which is not currently mandated by the aviation receiver performance standards.
08/2010;
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ABSTRACT: Peptoids, oligo-N-substituted glycines, can fold into well-defined helical secondary structures. The design and synthesis of new peptoid building blocks that are capable of both (a) inducing a helical secondary structure and (b) decorating the helices with chemical functionalities are reported. Peptoid heptamers containing carboxamide, carboxylic acid or thiol functionalities were synthesized, and the resulting peptoids were shown to form stable helices. A thiol-containing peptoid readily formed the homodisulfide, providing a convenient route to prepare peptoid helix homodimers.
Organic Letters 02/2010; 12(3):492-5. · 5.86 Impact Factor
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ABSTRACT: The chemoselective glycosylation of N-alkylaminooxy side chains with unprotected reducing sugars has proven useful for the synthesis of glycopeptides. Herein, we extend the N-alkylaminooxy strategy to the synthesis of glycopeptoids. A N-methylaminooxy submonomer was efficiently synthesized and incorporated into peptoids. Glycosylation of the peptoids proceeded chemoselectively and site-specifically at the N-methylaminooxy moieties. Employing microwave irradiation significantly increased the degree of glycosylation and shortened the reaction times.
Organic Letters 11/2009; 11(22):5210-3. · 5.86 Impact Factor
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ABSTRACT: A family of peptoid dimers developed to mimic SP-B is presented, where two amphipathic, cationic helices are linked by an achiral octameric chain. SP-B is a vital therapeutic protein in lung surfactant replacement therapy, but its large-scale isolation or chemical synthesis is impractical. Enhanced biomimicry of SP-B's disulfide-bonded structure has been previously attempted via disulfide-mediated dimerization of SP-B(1-25) and other peptide mimics, which improved surface activity relative to the monomers. Herein, the effects of disulfide- or "click"-mediated (1,3-dipolar cycloaddition) dimerization, as well as linker chemistry, on the lipid-associated surfactant activity of a peptoid monomer are described. Results revealed that the 'clicked' peptoid dimer enhanced in vitro surface activity in a DPPC:POPG:PA lipid film relative to its disulfide-bonded and monomeric counterparts in both surface balance and pulsating bubble surfactometry studies. On the pulsating bubble surfactometer, the film containing the "clicked" peptoid dimer outperformed all presented peptoid monomers and dimers, and two SP-B derived peptides, attaining an adsorbed surface tension of 22 mN m(-1), and maximum and minimum cycling values of 42 mN m(-1) and near-zero, respectively.
Biopolymers 09/2009; 92(6):538-53. · 2.87 Impact Factor
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ABSTRACT: Several prodrug approaches were taken to mask amino groups in two potent and selective neuronal nitric oxide synthase (nNOS) inhibitors containing either a primary or secondary amino group to lower the charge and improve blood-brain barrier (BBB) penetration. The primary amine was masked as an azide and the secondary amine as an amide or carbamate. The azide was not reduced to the amine under a variety of in vitro and ex vivo conditions. Despite the decrease in charge of the amino group as an amide and as carbamates, BBB penetration did not increase. It appears that the uses of azides as prodrugs for primary amines or amides and carbamates as prodrugs for secondary amines are not universally effective for CNS applications.
Bioorganic & medicinal chemistry 09/2009; 17(21):7593-605. · 2.82 Impact Factor
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ABSTRACT: 1] Deep and frequent fading of Global Positioning System (GPS) signals caused by ionospheric scintillation is a major concern for aircraft navigation using GPS in the equatorial region during solar maximum. Aviation receivers use both code and carrier measurements to calculate position solutions. Deep signal fading can break a receiver's carrier tracking lock to a satellite channel. The lost channel cannot be used for position calculation until the receiver reacquires the channel and reestablishes tracking. A solar maximum data set analyzed in this paper demonstrates frequent deep signal fading of almost all satellites in view. This could significantly reduce the number of simultaneous tracked satellites and consequently decrease navigation availability. Forty-five minutes of strong scintillation, which was the worst scintillation period of a 9 day campaign at Ascension Island in 2001, are analyzed in this paper. The importance of short reacquisition time of the receiver is described. In order to design an aviation receiver with short reacquisition time under frequent deep signal fading, the characteristics of signal fading should be well understood. Fading duration and the time between deep fades are two important characteristics for GPS navigation. This paper presents a fading duration model based on real scintillation data. The time between deep fades observed in this data shows very frequent deep fades which can significantly reduce benefit of carrier smoothing filters of aviation receivers., Characteristics of deep GPS signal fading due to ionospheric scintillation for aviation receiver design, Radio Sci., 44, RS0A16, doi:10.1029/2008RS004077.
01/2009;
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ABSTRACT: The neuronal isoform of nitric oxide synthase (nNOS), the enzyme responsible for the production of nitric oxide in the central nervous system, represents an attractive target for the treatment of various neurodegenerative disorders. X-ray crystal structures of complexes of nNOS with two nNOS-selective inhibitors, (4S)-N-{4-amino-5-[(2-aminoethylamino]pentyl}-N'-nitroguanidine (1) and 4-N-(Nomega-nitro-l-argininyl)-trans-4-amino-l-proline amide (2), led to the discovery of a conserved structural water molecule that was hydrogen bonded between the two heme propionates and the inhibitors (Figure 2). On the basis of this observation, we hypothesized that by attaching a hydrogen bond donor group to the amide nitrogen of 2 or to the secondary amine nitrogen of 1, the inhibitor molecules could displace the structural water molecule and obtain a direct interaction with the heme cofactor. To test this hypothesis, peptidomimetic analogues 3-5, which have either an N-hydroxyl (3 and 5) or N-amino (4) donor group, were designed and synthesized. X-ray crystal structures of nNOS with inhibitors 3 and 5 bound verified that the N-hydroxyl group had, indeed, displaced the structural water molecule and provided a direct interaction with the heme propionate moiety (Figures 5 and 6). Surprisingly, in vitro activity assay results indicated that the addition of a hydroxyl group (3) only increased the potency slightly against the neuronal isoform over the parent compound (1). Rationalizations for the small increase in potency are consistent with other changes in the crystal structures.
Journal of Medicinal Chemistry 05/2007; 50(9):2089-99. · 5.25 Impact Factor
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ABSTRACT: Selective inhibition of the localized excess production of NO by neuronal nitric oxide synthase (nNOS) has been targeted as a potential means of treating various neurological disorders. Based on observations from the X-ray crystal structures of complexes of nNOS with two nNOS-selective inhibitors, (4S)-N-{4-amino-5-[(2-amino)ethylamino]pentyl}-N'-nitroguanidine (L-Arg(NO2)-L-Dbu-NH2 (1) and 4-N-(Nomega-nitro-L-argininyl)-trans-4-amino-L-proline amide (2), a series of descarboxamide analogues was designed and synthesized (3-7). The most potent compound was aminopyrrolidine analogue 3, which exhibited better potency and selectivity for nNOS than parent compound 2. In addition, 3 provided higher lipophilicity and a lower molecular weight than 2, therefore having better physicochemical properties. Nalpha-Methylated analogues (8-11) also were prepared for increased lipophilicity of the inhibitors, but they had 4- to 5-fold weaker binding affinity compared to their parent compounds.
Bioorganic & Medicinal Chemistry 04/2007; 15(5):1928-38. · 2.92 Impact Factor
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ABSTRACT: The X-ray structure of previously studied dipeptidomimetic inhibitors bound in the active site of neuronal nitric oxide synthase (nNOS) presented a possibility for optimizing the strength of enzyme-inhibitor interactions as well as for enhancing bioavailability. These desirable properties may be attainable by replacement of the terminal amino group of the parent compounds (1-6) with a hydroxyl group (11-13, and 18-20). The hypothesized effect would be twofold: first, a change from a positively charged amino group to a neutral hydroxyl group might afford more drug-like character and blood-brain barrier permeability to the inhibitors; second, as suggested by docking studies, the incorporated hydroxyl group might displace an active site water molecule with which the terminal amino group of the original compounds indirectly hydrogen bonds. In vitro activity assays of the hydroxyl-terminated analogs (11-13 and 18-20) showed greater than an order of magnitude increase in K(i) values (decreased potency) relative to the amino-terminated compounds. These experimental data support the importance to enzyme binding of a potential electrostatic interaction relative to a hydrogen bonding interaction.
Bioorganic & Medicinal Chemistry 07/2006; 14(11):3681-90. · 2.92 Impact Factor
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ABSTRACT: This review includes the non-patent literature up to October 2004 that deals with selective neuronal nitric oxide synthase inhibitors (highest potency is for the neuronal isozyme). Some non-selective inhibitors or selective inducible nitric oxide synthase inhibitors are mentioned if they are related to compounds that are discussed; structures of these compounds generally are not given. In vitro inhibition constants are given either as IC(50) values or as K(i)values. An IC(50) value, the inhibitor concentration that produces 50% inhibition in the presence of a constant concentration of substrate, is obtained by extrapolation of several rate data points to 50% inhibition. K(i) values are derived from several types of plots that relate the concentration of inhibitor with enzyme velocity in the presence of a variety of substrate concentrations [1]. The K(i) value can be estimated from the IC(50) value [2]. Although the two inhibition constants are related, they are not the same; generally, the reported K(i) values tend to be lower than the IC(50) values. If specifics are desired about how the data were collected, then the reader will have to look in the literature cited. No attempt was made to be exhaustive in citing all references related to specific inhibitors; rather, examples of literature references are given for each inhibitor described.
Current Topics in Medicinal Chemistry 02/2005; 5(7):603-24. · 4.17 Impact Factor
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