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1.
Front Med (Lausanne) ; 10: 891513, 2023.
Article in English | MEDLINE | ID: mdl-36860338

ABSTRACT

Background: Calcineurin inhibitors (CNIs) are associated with nephrotoxicity, endothelial cell dysfunction, and thrombotic microangiopathy (TMA). Evolving evidence suggests an important role for complement dysregulation in the pathogenesis of CNI-induced TMA. However, the exact mechanism(s) of CNI-induced TMA remain(s) unknown. Methods: Using blood outgrowth endothelial cells (BOECs) from healthy donors, we evaluated the effects of cyclosporine on endothelial cell integrity. Specifically, we determined complement activation (C3c and C9) and regulation (CD46, CD55, CD59, and complement factor H [CFH] deposition) as these occurred on the endothelial cell surface membrane and glycocalyx. Results: We found that exposing the endothelium to cyclosporine resulted in a dose- and time-dependent enhancement of complement deposition and cytotoxicity. We, therefore, employed flow cytometry, Western blotting/CFH cofactor assays, and immunofluorescence imaging to determine the expression of complement regulators and the functional activity and localization of CFH. Notably, while cyclosporine led to the upregulation of complement regulators CD46, CD55, and CD59 on the endothelial cell surface, it also diminished the endothelial cell glycocalyx through the shedding of heparan sulfate side chains. The weakened endothelial cell glycocalyx resulted in decreased CFH surface binding and surface cofactor activity. Conclusion: Our findings confirm a role for complement in cyclosporine-induced endothelial injury and suggest that decreased glycocalyx density, induced by cyclosporine, is a mechanism that leads to complement alternative pathway dysregulation via decreased CFH surface binding and cofactor activity. This mechanism may apply to other secondary TMAs-in which a role for complement has so far not been recognized-and provide a potential therapeutic target and an important marker for patients on calcineurin inhibitors.

2.
Phys Rev Lett ; 125(6): 063401, 2020 Aug 07.
Article in English | MEDLINE | ID: mdl-32845680

ABSTRACT

We demonstrate microwave dressing on ultracold, fermionic ^{23}Na^{40}K ground-state molecules and observe resonant dipolar collisions with cross sections exceeding 3 times the s-wave unitarity limit. The origin of these interactions is the resonant alignment of the approaching molecules' dipoles along the intermolecular axis, which leads to strong attraction. We explain our observations with a conceptually simple two-state picture based on the Condon approximation. Furthermore, we perform coupled-channel calculations that agree well with the experimentally observed collision rates. The resonant microwave-induced collisions found here enable controlled, strong interactions between molecules, of immediate use for experiments in optical lattices.

3.
Phys Rev Lett ; 121(22): 225301, 2018 Nov 30.
Article in English | MEDLINE | ID: mdl-30547641

ABSTRACT

We study the critical vortex shedding in a strongly interacting fermionic superfluid of ^{6}Li across the BEC-BCS crossover. By moving an optical obstacle in the sample and directly imaging the vortices after the time of flight, the critical velocity u_{vor} for vortex shedding is measured as a function of the obstacle travel distance L. The observed u_{vor} increases with decreasing L, where the rate of increase is the highest in the unitary regime. In the deep Bose-Einstein condensation regime, an empirical dissipation model well captures the dependence of u_{vor} on L, characterized by a constant value of η=-[d(1/u_{vor})/d(1/L)]. However, as the system is tuned across the resonance, a step increase of η develops about a characteristic distance L_{c} as L is increased, where L_{c} is comparable to the obstacle size. This bimodal behavior is strengthened as the system is tuned towards the BCS regime. We attribute this evolution of u_{vor} to the emergence of the underlying fermionic degree of freedom in the vortex-shedding dynamics of a Fermi condensate.

4.
Science ; 357(6349): 372-375, 2017 07 28.
Article in English | MEDLINE | ID: mdl-28751602

ABSTRACT

Coherence, the stability of the relative phase between quantum states, is central to quantum mechanics and its applications. For ultracold dipolar molecules at sub-microkelvin temperatures, internal states with robust coherence are predicted to offer rich prospects for quantum many-body physics and quantum information processing. We report the observation of stable coherence between nuclear spin states of ultracold fermionic sodium-potassium (NaK) molecules in the singlet rovibrational ground state. Ramsey spectroscopy reveals coherence times on the scale of 1 second; this enables high-resolution spectroscopy of the molecular gas. Collisional shifts are shown to be absent down to the 100-millihertz level. This work opens the door to the use of molecules as a versatile quantum memory and for precision measurements on dipolar quantum matter.

5.
Phys Rev Lett ; 116(22): 225306, 2016 Jun 03.
Article in English | MEDLINE | ID: mdl-27314727

ABSTRACT

We demonstrate coherent microwave control of rotational and hyperfine states of trapped, ultracold, and chemically stable ^{23}Na^{40}K molecules. Starting with all molecules in the absolute rovibrational and hyperfine ground state, we study rotational transitions in combined magnetic and electric fields and explain the rich hyperfine structure. Following the transfer of the entire molecular ensemble into a single hyperfine level of the first rotationally excited state, J=1, we observe lifetimes of more than 3 s, comparable to those in the rovibrational ground state, J=0. Long-lived ensembles and full quantum state control are prerequisites for the use of ultracold molecules in quantum simulation, precision measurements, and quantum information processing.

6.
Phys Rev Lett ; 114(20): 205302, 2015 May 22.
Article in English | MEDLINE | ID: mdl-26047239

ABSTRACT

We report on the creation of an ultracold dipolar gas of fermionic 23Na40 K molecules in their absolute rovibrational and hyperfine ground state. Starting from weakly bound Feshbach molecules, we demonstrate hyperfine resolved two-photon transfer into the singlet X 1Σ+|v=0,J=0⟩ ground state, coherently bridging a binding energy difference of 0.65 eV via stimulated rapid adiabatic passage. The spin-polarized, nearly quantum degenerate molecular gas displays a lifetime longer than 2.5 s, highlighting NaK's stability against two-body chemical reactions. A homogeneous electric field is applied to induce a dipole moment of up to 0.8 D. With these advances, the exploration of many-body physics with strongly dipolar Fermi gases of 23Na40K molecules is within experimental reach.

7.
Phys Rev Lett ; 109(8): 085301, 2012 Aug 24.
Article in English | MEDLINE | ID: mdl-23002753

ABSTRACT

We report on the formation of ultracold weakly bound Feshbach molecules of 23Na40K, the first fermionic molecule that is chemically stable in its absolute ground state. The lifetime of the nearly degenerate molecular gas exceeds 100 ms in the vicinity of the Feshbach resonance. The measured dependence of the molecular binding energy on the magnetic field demonstrates the open-channel character of the molecules over a wide field range and implies significant singlet admixture. This will enable efficient transfer into the singlet vibrational ground state, resulting in a stable molecular Fermi gas with strong dipolar interactions.

8.
Nanotechnology ; 21(14): 145302, 2010 Apr 09.
Article in English | MEDLINE | ID: mdl-20215655

ABSTRACT

Recently, integrated flexible devices based on silicon nanowires (Si-NWs) have received significant attention as high performance flexible devices. However, most previous assembly methods can generate only specifically-shaped devices and require unconventional facilities, which has been a major hurdle for industrial applications. Herein, we report a simple but very efficient method for assembling Si-NWs into virtually generally-shape patterns on flexible substrates using only conventional microfabrication facilities, allowing us to mass-produce highly flexible low-noise devices. As proof of this method, we demonstrated the fabrication of highly bendable top-gate transistors based on Si-NWs. These devices showed typical n-type semiconductor behaviors, and exhibited a much lower noise level compared to previous flexible devices based on organic conductors or other nanowires. In addition, the gating behaviors and low-noise characteristics of our devices were maintained, even under highly bent conditions.

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