We experimentally realize a highly tunable superfluid oscillator circuit in a quantum gas of ultracold atoms and develop and verify a simple lumped-element description of this circuit. At low ...oscillator currents, we demonstrate that the circuit is accurately described as a Helmholtz resonator, a fundamental element of acoustic circuits. At larger currents, the breakdown of the Helmholtz regime is heralded by a turbulent shedding of vortices and density waves. Although a simple phase-slip model offers qualitative insights into the circuit's resistive behavior, our results indicate deviations from the phase-slip model. A full understanding of the dissipation in superfluid circuits will thus require the development of empirical models of the turbulent dynamics in this system, as have been developed for classical acoustic systems.
The ATP-sensitive K+ (KATP) channel is a key regulator of hormone secretion from pancreatic islet endocrine cells. Using direct measurements of KATP channel activity in pancreatic β cells and the ...lesser-studied α cells, from both humans and mice, we provide evidence that a glycolytic metabolon locally controls KATP channels on the plasma membrane. The two ATP-consuming enzymes of upper glycolysis, glucokinase and phosphofructokinase, generate ADP that activates KATP. Substrate channeling of fructose 1,6-bisphosphate through the enzymes of lower glycolysis fuels pyruvate kinase, which directly consumes the ADP made by phosphofructokinase to raise ATP/ADP and close the channel. We further show the presence of a plasma membrane-associated NAD+/NADH cycle whereby lactate dehydrogenase is functionally coupled to glyceraldehyde-3-phosphate dehydrogenase. These studies provide direct electrophysiological evidence of a KATP-controlling glycolytic signaling complex and demonstrate its relevance to islet glucose sensing and excitability.
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•KATP channels are regulated by a glycolytic metabolon on the plasma membrane•Substrate channeling occurs between the consecutive enzymes of glycolysis•Upper glycolysis produces ADP that is used directly by lower glycolysis to make ATP•LDH and GADPH facilitate a plasma membrane-associated NAD+/NADH redox cycle
Ho et al. provide evidence that glycolytic enzymes, including lactate dehydrogenase, form a plasma membrane-associated metabolon with intrinsic ATP/ADP and NAD+/NADH cycles. The subcellular location of this complex allows both ATP-consuming and ATP-producing enzymes to locally control the ATP-sensitive K+ channel in human and mouse pancreatic α and β cells.
•We consider an asset-based dynamic weapon-target assignment problem.•We assign interceptors to ballistic missiles in a multiple-salvo conflict situation.•We use approximate dynamic programming to ...obtain high quality fire control policies.•In a representative scenario, our policy achieves a 7.74% mean optimality gap.•Our work informs the development and evaluation of missile defense doctrine.
Given the ubiquitous nature of both offensive and defensive missile systems, the catastrophe-causing potential they represent, and the limited resources available to countries for missile defense, optimizing the defensive response to a missile attack is a necessary national security endeavor. For a single salvo of offensive missiles launched at a set of targets, a missile defense system protecting those targets must determine how many interceptors to fire at each incoming missile. Since such missile engagements often involve the firing of more than one attack salvo, we develop a Markov decision process (MDP) model to examine the optimal fire control policy for the defender. Due to the computational intractability of using exact methods for all but the smallest problem instances, we utilize an approximate dynamic programming (ADP) approach to explore the efficacy of applying approximate methods to the problem. We obtain policy insights by analyzing subsets of the state space that reflect a range of possible defender interceptor inventories. Testing of four instances derived from a representative planning scenario demonstrates that the ADP policy provides high-quality decisions for a majority of the state space, achieving a 7.74% mean optimality gap over all states for the most realistic instance, modeling a longer-term engagement by an attacker who assesses the success of each salvo before launching a subsequent one. Moreover, the ADP algorithm requires only a few minutes of computational effort versus hours for the exact dynamic programming algorithm, providing a method to address more complex and realistically-sized instances.
Altered metabotropic glutamate receptor 5 markers in PTSD Holmes, Sophie E.; Girgenti, Matthew J.; Davis, Margaret T. ...
Proceedings of the National Academy of Sciences - PNAS,
08/2017, Letnik:
114, Številka:
31
Journal Article
Recenzirano
Odprti dostop
Posttraumatic stress disorder (PTSD) is a prevalent and highly disabling disorder, but there is currently no targeted pharmacological treatment for it. Dysfunction of the glutamate system has been ...implicated in trauma and stress psychopathology, resulting in a growing interest in modulation of the glutamate system for the treatment of PTSD. Specifically, the metabotropic glutamate receptor 5 (mGluR5) represents a promising treatment target. We used 18FFPEB, a radioligand that binds to the mGluR5, and positron emission tomography (PET) to quantify in vivo mGluR5 availability in human PTSD vs. healthy control (HCs) subjects. In an independent sample of human postmortem tissue, we investigated expression of proteins that have a functional relationship with mGluR5 and glucocorticoids in PTSD. We observed significantly higher cortical mGluR5 availability in PTSD in vivo and positive correlations between mGluR5 availability and avoidance symptoms. In the postmortem sample, we observed up-regulation of SHANK1, a protein that anchors mGluR5 to the cell surface, as well as decreased expression of FKBP5, implicating aberrant glucocorticoid functioning in PTSD. Results of this study provide insight into molecular mechanisms underlying PTSD and suggest that mGluR5 may be a promising target for mechanism-based treatments aimed at mitigating this disorder.
To the Editor:
Hamdy and colleagues (April 27 issue)
1
report the 15-year outcomes of the Prostate Testing for Cancer and Treatment (ProtecT) trial, which involved a cohort of patients in the United ...Kingdom who were invited to undergo screening.
2
However, given the substantial differences in health care systems and patient case mixes between the United Kingdom and the United States, we feel compelled to comment on the generalizability of the results of this trial to a U.S. cohort. We interrogated our institutional database to find men 50 to 69 years of age in our health system who, between 1999 and . . .
Abstract
We present global 3D radiation magnetohydrodynamic simulations of accretion onto a 6.62 solar-mass black hole, with quasi-steady-state accretion rates reaching 0.016–0.9 times the critical ...accretion rate, which is defined as the accretion rate for powering the Eddington luminosity, assuming a 10% radiative efficiency, in three different runs. The simulations show no sign of thermal instability over hundreds of thermal timescales at 10
r
g
. The energy dissipation occurs close to the mid-plane in the near-critical runs and near the disk surface in the low–accretion rate run. The total radiative luminosity inside ∼20
r
g
is about 1%–30% of the Eddington limit, with radiative efficiencies of about 6% and 3%, respectively, in the sub- and near-critical accretion regimes. In both cases, self-consistent turbulence generated by the magnetorotational instability leads to angular momentum transfer, and the disk is supported by magnetic pressure. Outflows from the central low-density funnel, with a terminal velocity of ∼0.1
c
, are seen only in the near-critical runs. We conclude that these magnetic pressure–dominated disks are thermally stable and thicker than the
α
disk, and that the effective temperature profiles are much flatter than those in the
α
disks. The magnetic pressures of these disks are comparable within an order of magnitude to the previous analytical magnetic pressure–dominated disk model.
Abstract Background Microflora-dependent trimethylamine-N-oxide (TMAO) formation, which results from intake of choline and L-carnitine-rich food, shows promise as a predictor of cardiovascular ...disease (CVD) risk, but these associations have not been examined in ethnically diverse populations. In a multiethnic population-based study of adults in Canada, we assessed the stability of TMAO and L-carnitine in stored serum samples and their association with intimal medial thickness, prevalent risk factors, and clinical events. Methods In a randomly sampled cross-sectional study of 1286 Canadians, fasting serum samples were collected and stored. In 292 consecutive individuals (99 CVD cases and 193 unmatched control subjects), L-carnitine and TMAO concentrations were assessed using validated analytical approaches. Results The mean (± SD) TMAO level was 1.998 ± 3.13 μM and L-carnitine was 42.29 ± 11.35 μM. The relative levels of the samples did not appreciably change after 3 freeze-thaw cycles (coefficient of variation, 5.6% and 4.7%, respectively). No significant association between L-carnitine levels and prevalent CVD was found, with adjustment for covariates (odds ratio, 1.57; 95% confidence interval, 0.58-4.26; P trend = 0.65), for highest vs lowest quintile group. TMAO levels showed a significant, graded association with prevalent CVD (odds ratio, 3.17; 95% confidence interval, 1.05-9.51; P trend = 0.02). After further adjustment for diabetes status, meat, fish, and cholesterol intake, the association remained significant. No significant association between carotid intimal medial thickness and L-carnitine ( P = 0.64) or TMAO ( P = 0.18) was found. Conclusions Serum TMAO and L-carnitine analysis on stored samples is reliable. Our findings support an association between TMAO with prevalent CVD in a multiethnic population. This finding requires replication in larger studies in which dietary intake and stored serum samples exist.
We introduce a new method of statistical analysis to characterize the dynamics of turbulent fluids in two dimensions. We establish that, in equilibrium, the vortex distributions can be uniquely ...connected to the temperature of the vortex gas, and we apply this vortex thermometry to characterize simulations of decaying superfluid turbulence. We confirm the hypothesis of vortex evaporative heating leading to Onsager vortices proposed in Phys. Rev. Lett. 113, 165302 (2014)PRLTAO0031-900710.1103/PhysRevLett.113.165302, and we find previously unidentified vortex power-law distributions that emerge from the dynamics.
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