Combination quetiapine therapy in the long-term treatment of patients with bipolar I disorder

OBJECTIVE: Determine the long-term effectiveness of quetiapine in combination with standard treatments in preventing relapses for patients with bipolar I disorders METHOD: Twenty-one outpatients with type I bipolar disorder who had inadequate responses to ongoing standard therapies were treated with add-on quetiapine in an open-label study. The quetiapine dose was increased until clinical response occurred. Illness response was assessed using the Clinical Global Impression (CGI) scale. Relapse rates before and during quetiapine treatment were compared by calculating incidence risk ratios. RESULTS: Quetiapine was added to ongoing standard therapy for 26 to 78 weeks. Thirteen patients received combination therapy for at least 52 weeks. The mean quetiapine dose received was 518 ± 244 mg/day. There were highly significant improvements in overall relapse rate, manic/mixed relapse rate, and depression relapse rate in the period during quetiapine treatment compared with the period before quetiapine was initiated. The calculated relative risk of relapse in the absence of quetiapine treatment was 2.9 overall (95% confidence interval, 1.5~5.6), 3.3 for manic/mixed relapse (95% confidence interval, 1.5~7.1), and 2.4 for depressive relapse (95% confidence interval, 1.3~4.4). The mean Clinical Global Impression scores improved significantly from baseline during 26 weeks of quetiapine treatment in 21 patients (p = 0.002) and remained significantly better during a 52-week treatment period in 13 patients (p = 0.036). CONCLUSION: Long-term treatment with quetiapine combination therapy reduced the probability of manic/mixed and depressive relapses and improved symptoms in patients with bipolar I disorder who had inadequate responses to ongoing standard treatment

The Role of SurA PPIase Domains in Preventing Aggregation of the Outer Membrane Proteins tOmpA and OmpT

SurA is a conserved ATP-independent periplasmic chaperone involved in the biogenesis of outer-membrane proteins (OMPs). Escherichia coli SurA has a core domain and two peptidylprolyl isomerase (PPIase) domains, the role(s) of which remain unresolved. Here we show that while SurA homologues in early proteobacteria typically contain one or no PPIase domains, the presence of two PPIase domains is common in SurA in later proteobacteria, implying an evolutionary advantage for this domain architecture. Bioinformatics analysis of > 350,000 OMP sequences showed that their length, hydrophobicity and aggregation propensity are similar across the proteobacterial classes, ruling out a simple correlation between SurA domain architecture and these properties of OMP sequences. To investigate the role of the PPIase domains in SurA activity, we deleted one or both PPIase domains from E. coli SurA and investigated the ability of the resulting proteins to bind and prevent the aggregation of tOmpA (19 kDa) and OmpT (33 kDa). The results show that wild-type SurA inhibits the aggregation of both OMPs, as do the cytoplasmic OMP chaperones trigger factor and SecB. However, while the ability of SurA to bind and prevent tOmpA aggregation does not depend on its PPIase domains, deletion of even a single PPIase domain ablates the ability of SurA to prevent OmpT aggregation. The results demonstrate that the core domain of SurA endows its generic chaperone ability, while the presence of PPIase domains enhances its chaperone activity for specific OMPs, suggesting one reason for the conservation of multiple PPIase domains in SurA in proteobacteria

Extended Lifetime in Computational Evolution of Isolated Black Holes

Solving the 4-d Einstein equations as evolution in time requires solving equations of two types: the four elliptic initial data (constraint) equations, followed by the six second order evolution equations. Analytically the constraint equations remain solved under the action of the evolution, and one approach is to simply monitor them ({\it unconstrained} evolution). The problem of the 3-d computational simulation of even a single isolated vacuum black hole has proven to be remarkably difficult. Recently, we have become aware of two publications that describe very long term evolution, at least for single isolated black holes. An essential feature in each of these results is {\it constraint subtraction}. Additionally, each of these approaches is based on what we call "modern," hyperbolic formulations of the Einstein equations. It is generally assumed, based on computational experience, that the use of such modern formulations is essential for long-term black hole stability. We report here on comparable lifetime results based on the much simpler ("traditional") $\dot g$ - $\dot K$ formulation. We have also carried out a series of {\it constrained} 3-d evolutions of single isolated black holes. We find that constraint solution can produce substantially stabilized long-term single hole evolutions. However, we have found that for large domains, neither constraint-subtracted nor constrained $\dot g$ - $\dot K$ evolutions carried out in Cartesian coordinates admit arbitrarily long-lived simulations. The failure appears to arise from features at the inner excision boundary; the behavior does generally improve with resolution.Comment: 20 pages, 6 figure

Broadband laser cooling of trapped atoms with ultrafast pulses

We demonstrate broadband laser cooling of atomic ions in an rf trap using ultrafast pulses from a modelocked laser. The temperature of a single ion is measured by observing the size of a time-averaged image of the ion in the known harmonic trap potential. While the lowest observed temperature was only about 1 K, this method efficiently cools very hot atoms and can sufficiently localize trapped atoms to produce near diffraction-limited atomic images

Holographic evolution of the mutual information

We compute the time evolution of the mutual information in out of equilibrium quantum systems whose gravity duals are Vaidya spacetimes in three and four dimensions, which describe the formation of a black hole through the collapse of null dust. We find the holographic mutual information to be non monotonic in time and always monogamous in the ranges explored. We also find that there is a region in the configuration space where it vanishes at all times. We show that the null energy condition is a necessary condition for both the strong subadditivity of the holographic entanglement entropy and the monogamy of the holographic mutual information.Comment: 32 pages, 16 figure

Adjusted ADM systems and their expected stability properties: constraint propagation analysis in Schwarzschild spacetime

In order to find a way to have a better formulation for numerical evolution of the Einstein equations, we study the propagation equations of the constraints based on the Arnowitt-Deser-Misner formulation. By adjusting constraint terms in the evolution equations, we try to construct an "asymptotically constrained system" which is expected to be robust against violation of the constraints, and to enable a long-term stable and accurate numerical simulation. We first provide useful expressions for analyzing constraint propagation in a general spacetime, then apply it to Schwarzschild spacetime. We search when and where the negative real or non-zero imaginary eigenvalues of the homogenized constraint propagation matrix appear, and how they depend on the choice of coordinate system and adjustments. Our analysis includes the proposal of Detweiler (1987), which is still the best one according to our conjecture but has a growing mode of error near the horizon. Some examples are snapshots of a maximally sliced Schwarzschild black hole. The predictions here may help the community to make further improvements.Comment: 23 pages, RevTeX4, many figures. Revised version. Added subtitle, reduced figures, rephrased introduction, and a native checked. :-

Positivity, entanglement entropy, and minimal surfaces

The path integral representation for the Renyi entanglement entropies of integer index n implies these information measures define operator correlation functions in QFT. We analyze whether the limit $n\rightarrow 1$, corresponding to the entanglement entropy, can also be represented in terms of a path integral with insertions on the region's boundary, at first order in $n-1$. This conjecture has been used in the literature in several occasions, and specially in an attempt to prove the Ryu-Takayanagi holographic entanglement entropy formula. We show it leads to conditional positivity of the entropy correlation matrices, which is equivalent to an infinite series of polynomial inequalities for the entropies in QFT or the areas of minimal surfaces representing the entanglement entropy in the AdS-CFT context. We check these inequalities in several examples. No counterexample is found in the few known exact results for the entanglement entropy in QFT. The inequalities are also remarkable satisfied for several classes of minimal surfaces but we find counterexamples corresponding to more complicated geometries. We develop some analytic tools to test the inequalities, and as a byproduct, we show that positivity for the correlation functions is a local property when supplemented with analyticity. We also review general aspects of positivity for large N theories and Wilson loops in AdS-CFT.Comment: 36 pages, 10 figures. Changes in presentation and discussion of Wilson loops. Conclusions regarding entanglement entropy unchange

Detection of the pairwise kinematic Sunyaev-Zel'dovich effect with BOSS DR11 and the Atacama Cosmology Telescope

We present a new measurement of the kinematic Sunyaev-Zeldovich effect using data from the Atacama Cosmology Telescope (ACT) and the Baryon Oscillation Spectroscopic Survey (BOSS). Using 600 square degrees of overlapping sky area, we evaluate the mean pairwise baryon momentum associated with the positions of 50,000 bright galaxies in the BOSS DR11 Large Scale Structure catalog. A non-zero signal arises from the large-scale motions of halos containing the sample galaxies. The data fits an analytical signal model well, with the optical depth to microwave photon scattering as a free parameter determining the overall signal amplitude. We estimate the covariance matrix of the mean pairwise momentum as a function of galaxy separation, using microwave sky simulations, jackknife evaluation, and bootstrap estimates. The most conservative simulation-based errors give signal-to-noise estimates between 3.6 and 4.1 for varying galaxy luminosity cuts. We discuss how the other error determinations can lead to higher signal-to-noise values, and consider the impact of several possible systematic errors. Estimates of the optical depth from the average thermal Sunyaev-Zeldovich signal at the sample galaxy positions are broadly consistent with those obtained from the mean pairwise momentum signal.Comment: 15 pages, 8 figures, 2 table

Inter-domain dynamics in the chaperone SurA and multi-site binding to its outer membrane protein clients

The periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis. E. coli SurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but its mechanisms of client binding and chaperone function have remained unclear. Here, we use chemical cross-linking, hydrogen-deuterium exchange mass spectrometry, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and interrogate the role of conformational dynamics in OMP recognition. We demonstrate that SurA samples an array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested in the SurA crystal structure. OMP binding sites are located primarily in the core domain, and OMP binding results in conformational changes between the core/P1 domains. Together, the results suggest that unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between domains assisting OMP recognition, binding and release