TY - JOUR
AB - The human norepinephrine (NE) transporter (hNET) attenuates neuronal signaling by rapid NE clearance from the synaptic cleft, and NET is a target for cocaine and amphetamines as well as therapeutics for depression, obsessive-compulsive disorder, and post-traumatic stress disorder. In spite of its central importance in the nervous system, little is known about how NET substrates, such as NE, 1-methyl-4-tetrahydropyridinium (MPP+), or amphetamine, interact with NET at the molecular level. Nor do we understand the mechanisms behind the transport rate. Previously we introduced a fluorescent substrate similar to MPP+, which allowed separate and simultaneous binding and transport measurement (Schwartz, J. W., Blakely, R. D., and DeFelice, L. J. (2003) J. Biol. Chem. 278, 9768-9777). Here we use this substrate, 4-(4-(dimethylamino)styrl)-N-methyl-pyridinium (ASP+), in combination with green fluorescent protein-tagged hNETs to measure substrate-transporter stoichiometry and substrate binding kinetics. Calibrated confocal microscopy and fluorescence correlation spectroscopy reveal that hNETs, which are homo-multimers, bind one substrate molecule per transporter subunit. Substrate residence at the transporter, obtained from rapid on-off kinetics revealed in fluorescence correlation spectroscopy, is 526 μs. Substrate residence obtained by infinite dilution is 1000 times slower. This novel examination of substrate-transporter kinetics indicates that a single ASP + molecule binds and unbinds thousands of times before being transported or ultimately dissociated from hNET. Calibrated fluorescent images combined with mass spectroscopy give a transport rate of 0.06 ASP +/hNET-protein/s, thus 36,000 on-off binding events (and 36 actual departures) occur for one transport event. Therefore binding has a low probability of resulting in transport. We interpret these data to mean that inefficient binding could contribute to slow transport rates.
AU - Schwartz, Joel W
AU - Gaia Novarino
AU - Piston, David W
AU - DeFelice, Louis J
ID - 2307
IS - 19
JF - Journal of Biological Chemistry
TI - Substrate binding stoichiometry and kinetics of the norepinephrine transporter
VL - 280
ER -
TY - BOOK
AB - This book contains a unique survey of the mathematically rigorous results about the quantum-mechanical many-body problem that have been obtained by the authors in the past seven years. It addresses a topic that is not only rich mathematically, using a large variety of techniques in mathematical analysis, but is also one with strong ties to current experiments on ultra-cold Bose gases and Bose-Einstein condensation. The book provides a pedagogical entry into an active area of ongoing research for both graduate students and researchers. It is an outgrowth of a course given by the authors for graduate students and post-doctoral researchers at the Oberwolfach Research Institute in 2004. The book also provides a coherent summary of the field and a reference for mathematicians and physicists active in research on quantum mechanics.
AU - Lieb, Élliott H
AU - Robert Seiringer
AU - Solovej, Jan P
AU - Yngvason, Jakob
ID - 2335
T2 - The mathematics of the Bose gas and its condensation
TI - The mathematics of the Bose gas and its condensation
VL - 34
ER -
TY - CHAP
AB -
Now that the low temperature properties of quantum-mechanical many-body systems (bosons) at low density, ρ, can be examined experimentally it is appropriate to revisit some of the formulas deduced by many authors 4–5 decades ago, and to explore new regimes not treated before. For systems with repulsive (i.e. positive) interaction potentials the experimental low temperature state and the ground state are effectively synonymous — and this fact is used in all modeling. In such cases, the leading term in the energy/particle is 2πħ2 aρ/m where a is the scattering length of the two-body potential. Owing to the delicate and peculiar nature of bosonic correlations (such as the strange N 7/5 law for charged bosons), four decades of research failed to establish this plausible formula rigorously. The only previous lower bound for the energy was found by Dyson in 1957, but it was 14 times too small. The correct asymptotic formula has been obtained by us and this work will be presented. The reason behind the mathematical difficulties will be emphasized. A different formula, postulated as late as 1971 by Schick, holds in two dimensions and this, too, will be shown to be correct. With the aid of the methodology developed to prove the lower bound for the homogeneous gas, several other problems have been successfully addressed. One is the proof by us that the Gross-Pitaevskii equation correctly describes the ground state in the ‘traps’ actually used in the experiments. For this system it is also possible to prove complete Bose condensation and superfluidity as we have shown. On the frontier of experimental developments is the possibility that a dilute gas in an elongated trap will behave like a one-dimensional system; we have proved this mathematically. Another topic is a proof that Foldy’s 1961 theory of a high density Bose gas of charged particles correctly describes its ground state energy; using this we can also prove the N 7/5 formula for the ground state energy of the two-component charged Bose gas proposed by Dyson in 1967. All of this is quite recent work and it is hoped that the mathematical methodology might be useful, ultimately, to solve more complex problems connected with these interesting systems.
AU - Lieb, Élliott H
AU - Robert Seiringer
AU - Solovej, Jan P
AU - Yngvason, Jakob
ED - Benedicks, Michael
ED - Jones, Peter W
ED - Smirnov, Stanislav
ED - Winckler, Björn
ID - 2336
T2 - Perspectives in Analysis
TI - The quantum-mechanical many-body problem: The Bose gas
VL - 27
ER -
TY - JOUR
AB - The validity of substituting a c-number z for the k = 0 mode operator a0 is established rigorously in full generality, thereby verifying one aspect of Bogoliubov's 1947 theory. This substitution not only yields the correct value of thermodynamic quantities such as the pressure or ground state energy, but also the value of |z|2 that maximizes the partition function equals the true amount of condensation in the presence of a gauge-symmetry-breaking term. This point had previously been elusive.
AU - Lieb, Élliott H
AU - Robert Seiringer
AU - Yngvason, Jakob
ID - 2359
IS - 8
JF - Physical Review Letters
TI - Justification of c-number substitutions in bosonic hamiltonians
VL - 94
ER -
TY - JOUR
AB - The strong subadditivity of entropy plays a key role in several areas of physics and mathematics. It states that the entropy S[±]=- Tr(Ï±lnÏ±) of a density matrix Ï±123 on the product of three Hilbert spaces satisfies S[Ï±123]- S[Ï±12]≤S[Ï±23]-S[Ï±2]. We strengthen this to S[Ï±123]-S[Ï±12] ≤αnα(S[Ï±23α]-S[Ï±2α]), where the nα are weights and the Ï±23α are partitions of Ï±23. Correspondingly, there is a strengthening of the theorem that the map A|Trexp[L+lnA] is concave. As applications we prove some monotonicity and convexity properties of the Wehrl coherent state entropy and entropy inequalities for quantum gases.
AU - Lieb, Élliott H
AU - Robert Seiringer
ID - 2361
IS - 6
JF - Physical Review A - Atomic, Molecular, and Optical Physics
TI - Stronger subadditivity of entropy
VL - 71
ER -