Understanding the in vivo Uptake Kinetics of a Phosphatidylethanolamine-binding Agent \u3csup\u3e99m\u3c/sup\u3eTc-Duramycin

Introduction 99mTc-Duramycin is a peptide-based molecular probe that binds specifically to phosphatidylethanolamine (PE). The goal was to characterize the kinetics of molecular interactions between 99mTc-Duramycin and the target tissue. Methods High level of accessible PE is induced in cardiac tissues by myocardial ischemia (30 min) and reperfusion (120 min) in Sprague–Dawley rats. Target binding and biodistribution of 99mTc-duramycin were captured using SPECT/CT. To quantify the binding kinetics, the presence of radioactivity in ischemic versus normal cardiac tissues was measured by gamma counting at 3, 10, 20, 60 and 180 min after injection. A partially inactivated form of 99mTc-Duramycin was analyzed in the same fashion. A compartment model was developed to quantify the uptake kinetics of 99mTc-Duramycin in normal and ischemic myocardial tissue. Results 99mTc-duramycin binds avidly to the damaged tissue with a high target-to-background radio. Compartment modeling shows that accessibility of binding sites in myocardial tissue to 99mTc-Duramycin is not a limiting factor and the rate constant of target binding in the target tissue is at 2.2 ml/nmol/min/g. The number of available binding sites for 99mTc-Duramycin in ischemic myocardium was estimated at 0.14 nmol/g. Covalent modification of D15 resulted in a 9-fold reduction in binding affinity. Conclusion 99mTc-Duramycin accumulates avidly in target tissues in a PE-dependent fashion. Model results reflect an efficient uptake mechanism, consistent with the low molecular weight of the radiopharmaceutical and the relatively high density of available binding sites. These data help better define the imaging utilities of 99mTc-Duramycin as a novel PE-binding agent

Project Evaluation and Selection with Task Failures

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154433/1/poms13107_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154433/2/poms13107.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154433/3/poms13107-sup-0001-Appendix.pd

Exchange and correlation near the nucleus in density functional theory

The near nucleus behavior of the exchange-correlation potential $v_{xc}({\bf r})$ in Hohenberg-Kohn-Sham density functional theory is investigated. It is shown that near the nucleus the linear term of $O(r)$ of the spherically averaged exchange-correlation potential ${\bar v}_{xc}(r)$ is nonzero, and that it arises purely from the difference between the kinetic energy density at the nucleus of the interacting system and the noninteracting Kohn-Sham system. An analytical expression for the linear term is derived. Similar results for the exchange $v_{x}({\bf r})$ and correlation $v_{c}({\bf r})$ potentials are also obtained separately. It is further pointed out that the linear term in $v_{xc}({\bf r})$ arising mainly from $v_{c}({\bf r})$ is rather small, and $v_{xc}({\bf r})$ therefore has a nearly quadratic structure near the nucleus. Implications of the results for the construction of the Kohn-Sham system are discussed with examples.Comment: 10 page

IC 225: a dwarf elliptical galaxy with a peculiar blue core

We present the discovery of a peculiar blue core in the elliptical galaxy IC 225 by using images and spectrum from the Sloan Digital Sky Survey (SDSS). The outer parts of the surface brightness profiles of u-, g-, r-, i- and z-band SDSS images for IC 225 are well fitted with an exponential function. The fitting results show that IC 225 follows the same relations between the magnitude, scale length and central surface brightness for dwarf elliptical galaxies. Its absolute blue magnitude (M_B) is -17.14 mag, all of which suggest that IC 225 is a typical dwarf elliptical galaxy. The g-r color profile indicates a very blue core with a radius of 2 arcseconds, which is also clearly seen in the RGB image made of g-, r- and i-band SDSS images. The SDSS optical spectrum exhibits strong and very narrow nebular emission lines. The metal abundances derived by the standard methods, which are 12+log(O/H) = 8.98, log(N/O) = -0.77 and 12+log(S+/H+) = 6.76, turn out to be significantly higher than that predicted by the well-known luminosity-metallicity relation. After carefully inspecting the central region of IC 225, we find that there are two distinct nuclei, separated by 1.4 arcseconds, the off-nucleated one is even bluer than the nucleus of IC 225. The asymmetric line profiles of higher-order Balmer lines indicate that the emission lines are bluer shifted relative to the absorption lines, suggesting that the line emission arises from the off-center core, whose nature is a metal-rich Hii region. To the best of our knowledge, it is the first high-metallicity Hii region detected in a dwarf elliptical galaxy.Comment: 7 figures, accepted for publication in A

Information Systems and Health Care IX: Accessing Tacit Knowledge and Linking It to the Peer-Reviewed Literature

Clinical decision-making can be improved if healthcare practitioners are able to leverage both the tacit and explicit modalities of healthcare knowledge, yet at present there do not exist knowledge management systems that support any active and direct mapping between these two knowledge modalities. In this paper, we present a healthcare knowledge-mapping framework that maps (a) the tacit knowledge captured in terms of email-based discussions between pediatric pain practitioners through a Pediatric Pain Mailing List (PPML), to (b) explicit knowledge represented in terms of peer-reviewed healthcare literature available at PubMed. We report our knowledge mapping strategy that involves methods to establish discussion threads, organize the discussion threads in terms of topic-specific taxonomy, formulate an optimal search query based on the content of a discussion thread, submit the search query to PubMed and finally to retrieve and present the search results to the user

The on-top pair-correlation density in the homogeneous electron liquid

The ladder theory, in which the Bethe-Goldstone equation for the effective potential between two scattering particles plays a central role, is well known for its satisfactory description of the short-range correlations in the homogeneous electron liquid. By solving exactly the Bethe-Goldstone equation in the limit of large transfer momentum between two scattering particles, we obtain accurate results for the on-top pair-correlation density $g(0)$, in both three dimensions and two dimensions. Furthermore, we prove, in general, the ladder theory satisfies the cusp condition for the pair-correlation density $g(r)$ at zero distance $r=0$.Comment: 8 pages, 4 figure

Charge-state dependent vibrational relaxation in a single-molecule junction

The interplay between nuclear and electronic degrees of freedom strongly influences molecular charge transport. Herein, we report on transport through a porphyrin dimer molecule, weakly coupled to graphene electrodes, that displays sequential tunneling within the Coulomb-blockade regime. The sequential transport is initiated by current-induced phonon absorption and proceeds by rapid sequential transport via a non-equilibrium vibrational distribution. We demonstrate this is possible only when the vibrational dissipation is slow relative to sequential tunneling rates, and obtain a lower bound for the vibrational relaxation time of 8 ns, a value that is dependent on the molecular charge state.Comment: 8 pages, 7 figure