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Biomedical subjects

Kevin L Moore

Publications and source records attributed to Kevin L Moore.

8 recordsLinked to original sources

Probing the quantum state of a guided atom laser pulse.

We describe bichromatic superradiant pump-probe spectroscopy as a tomographic probe of the Wigner function of a dispersing particle beam. We employed this technique to characterize the quantum state of an ultracold atomic beam, derived from a 87Rb Bose-Einstein condensate, as it propagated in a 2.5 mm diameter circular waveguide. Our measurements place an upper bound on the longitudinal phase space area occupied by the 3 x 10(5) atom beam of 9(1)Planck's constant and a lower bound on the coherence length of L>or=13(1) microm. These results are consistent with full quantum degeneracy after multiple orbits around the waveguide.

Journal Article↗

Detection and purification of tyrosine-sulfated proteins using a novel anti-sulfotyrosine monoclonal antibody.

Protein tyrosine O-sulfation is a post-translational modification mediated by one of two Golgi tyrosylprotein sulfotransferases (TPST1 and TPST2) that catalyze the transfer of sulfate to tyrosine residues in secreted and transmembrane proteins. Tyrosine sulfation plays a role in protein-protein interactions in several well defined systems. Although dozens of tyrosine-sulfated proteins are known, many more are likely to exist and await description. Advancing our understanding of the importance of tyrosine sulfation in biological systems requires the development of new tools for the detection and study of tyrosine-sulfated proteins. We have developed a novel anti-sulfotyrosine monoclonal antibody (called PSG2) that binds with high affinity and exquisite specificity to sulfotyrosine residues in peptides and proteins independently of sequence context. We show that it can detect tyrosine-sulfated proteins in complex biological samples and can be used as a probe to assess the role of tyrosine sulfation in protein function. We also demonstrate the utility of PSG2 in the purification of tyrosine-sulfated proteins from crude tissue samples. Finally, Western blot analysis using PSG2 showed that certain sperm/epididymal proteins are undersulfated in Tpst2(-/-) mice. This indicates that TPST1 and TPST2 have distinct macromolecular substrate specificities and provides clues as to the molecular mechanism of the infertility of Tpst2(-/-) males. PSG2 should be widely applicable for identification of tyrosine-sulfated proteins in other systems and organisms.

Animals↗

Targeted disruption of tyrosylprotein sulfotransferase-2, an enzyme that catalyzes post-translational protein tyrosine O-sulfation, causes male infertility.

Tyrosine O-sulfation is a post-translational modification mediated by one of two Golgi tyrosylprotein sulfotransferases (TPST-1 and -2) expressed in all mammalian cells. Tyrosine sulfation plays an important role in the function of some known TPST substrates by enhancing protein-protein interactions. To explore the role of these enzymes in vivo and gain insight into other potential TPST substrates, TPST-2-deficient mice were generated by targeted disruption of the Tpst2 gene. Tpst2(+/-) mice appear normal and, when interbred, yield litters of normal size with a Mendelian distribution of the targeted mutation. Tpst2(-/-) mice have moderately delayed growth but appear healthy and attain normal body weight by 10 weeks of age. In contrast to Tpst1(-/-) males that have normal fertility, Tpst2(-/-) males are infertile. Tpst2(-/-) sperm are normal in number, morphology, and motility in normal media and appear to capacitate and undergo acrosomal exocytosis normally. However, they are severely defective in their motility in viscous media and in their ability to fertilize zona pellucida-intact eggs. Adhesion of Tpst2(-/-) sperm to the egg plasma membrane is reduced compared with wild type sperm, but sperm-egg fusion is similar or even increased. These data strongly suggest that tyrosine sulfation of unidentified substrate(s) play a crucial role in these processes and document for the first time the critical importance of post-translational tyrosine sulfation in male fertility.

Animals↗

Relay feedback tuning of robust PID controllers with iso-damping property.

A new tuning method for proportional-integral-derivative (PID) controller design is proposed for a class of unknown, stable, and minimum phase plants. We are able to design a PID controller to ensure that the phase Bode plot is flat, i.e., the phase derivative w.r.t. the frequency is zero, at a given frequency called the "tangent frequency" so that the closed-loop system is robust to gain variations and the step responses exhibit an iso-damping property. At the "tangent frequency," the Nyquist curve tangentially touches the sensitivity circle. Several relay feedback tests are used to identify the plant gain and phase at the tangent frequency in an iterative way. The identified plant gain and phase at the desired tangent frequency are used to estimate the derivatives of amplitude and phase of the plant with respect to frequency at the same frequency point by Bode's integral relationship. Then, these derivatives are used to design a PID controller for slope adjustment of the Nyquist plot to achieve the robustness of the system to gain variations. No plant model is assumed during the PID controller design. Only several relay tests are needed. Simulation examples illustrate the effectiveness and the simplicity of the proposed method for robust PID controller design with an iso-damping property.

Algorithms↗

Learning feedforward control using a dilated B-spline network: frequency domain analysis and design.

This paper presents a frequency-domain analysis and design approach for a learning feedforward controller (LFFC) using a dilated B-spline network. The LFFC acts as an add-on element to the existing feedback controller (FBC). The LFFC signal is updated iteratively based on the FBC signal of the previous iteration as the task repeats. Similar to proportional-integral-derivative controller tuning, there are only two parameters to adjust: The B-spline support width and the learning gain. The effect of dilation in the B-spline network is discussed. Detailed design formulae are given based on a stability analysis. As an illustration, simulation results on the path tracking control of a wheeled mobile robot are presented.

Artificial Intelligence↗

Reduced body weight and increased postimplantation fetal death in tyrosylprotein sulfotransferase-1-deficient mice.

Tyrosine sulfation is mediated by one of two Golgi isoenzymes, called tyrosylprotein sulfotransferases (TPST-1 and TPST-2). A relatively small number of proteins are known to undergo tyrosine sulfation, including certain adhesion molecules, G-protein-coupled receptors, coagulation factors, serpins, extracellular matrix proteins, and hormones. As one approach to explore the role of these enzymes in vivo and how they might interact in biological systems, we have generated TPST-1-deficient mice by targeted disruption of the Tpst1 gene. Tpst1(+/-) mice appear normal and, when interbred, yield litters of normal size with a Mendelian genetic distribution and an equal sex distribution. Tpst1(-/-) mice appear healthy but have approximately 5% lower average body weight than Tpst1(+/+) controls. In addition, we show that although fertility of Tpst1(-/-) males and females per se is normal, Tpst1(-/-) females have significantly smaller litters because of fetal death between 8.5 and 15.5 days postcoitum. These findings suggest that there are proteins involved in regulation of body weight and reproductive physiology, which require tyrosine sulfation for optimal function that are yet to be described. Our findings also strongly support the conclusion that TPST-1 and TPST-2 have distinct biological roles that may reflect differences in their macromolecular substrate specificity.

Animals↗