An Exact Algorithm for Side-Chain Placement in Protein Design

Computational protein design aims at constructing novel or improved functions on the structure of a given protein backbone and has important applications in the pharmaceutical and biotechnical industry. The underlying combinatorial side-chain placement problem consists of choosing a side-chain placement for each residue position such that the resulting overall energy is minimum. The choice of the side-chain then also determines the amino acid for this position. Many algorithms for this NP-hard problem have been proposed in the context of homology modeling, which, however, reach their limits when faced with large protein design instances. In this paper, we propose a new exact method for the side-chain placement problem that works well even for large instance sizes as they appear in protein design. Our main contribution is a dedicated branch-and-bound algorithm that combines tight upper and lower bounds resulting from a novel Lagrangian relaxation approach for side-chain placement. Our experimental results show that our method outperforms alternative state-of-the art exact approaches and makes it possible to optimally solve large protein design instances routinely

Dispersive properties of quasi-phase-matched optical parametric amplifiers

The dispersive properties of non-degenerate optical parametric amplification in quasi-phase-matched (QPM) nonlinear quadratic crystals with an arbitrary grating profile are theoretically investigated in the no-pump-depletion limit. The spectral group delay curve of the amplifier is shown to be univocally determined by its spectral power gain curve through a Hilbert transform. Such a constraint has important implications on the propagation of spectrally-narrow optical pulses through the amplifier. In particular, it is shown that anomalous transit times, corresponding to superluminal or even negative group velocities, are possible near local minima of the spectral gain curve. A possible experimental observation of such effects using a QPM Lithium-Niobate crystal is suggested.Comment: submitted for publicatio

Dynamical stability of infinite homogeneous self-gravitating systems: application of the Nyquist method

We complete classical investigations concerning the dynamical stability of an infinite homogeneous gaseous medium described by the Euler-Poisson system or an infinite homogeneous stellar system described by the Vlasov-Poisson system (Jeans problem). To determine the stability of an infinite homogeneous stellar system with respect to a perturbation of wavenumber k, we apply the Nyquist method. We first consider the case of single-humped distributions and show that, for infinite homogeneous systems, the onset of instability is the same in a stellar system and in the corresponding barotropic gas, contrary to the case of inhomogeneous systems. We show that this result is true for any symmetric single-humped velocity distribution, not only for the Maxwellian. If we specialize on isothermal and polytropic distributions, analytical expressions for the growth rate, damping rate and pulsation period of the perturbation can be given. Then, we consider the Vlasov stability of symmetric and asymmetric double-humped distributions (two-stream stellar systems) and determine the stability diagrams depending on the degree of asymmetry. We compare these results with the Euler stability of two self-gravitating gaseous streams. Finally, we determine the corresponding stability diagrams in the case of plasmas and compare the results with self-gravitating systems

Taenia solium Cysticercosis, Irian Jaya, Indonesia

Centers for Disease Control and Prevention, Toni, Wandra ; Akira, Ito ; Hiroshi, Yamasaki ; Thomas, Suroso ; Sri S. Margono, Emerging Infectious Diseases, 9(7), 2003, 884-885. publishe

Relating the CMSSM and SUGRA models with GUT scale and Super-GUT scale Supersymmetry Breaking

While the constrained minimal supersymmetric standard model (CMSSM) with universal gaugino masses, m_{1/2}, scalar masses, m_0, and A-terms, A_0, defined at some high energy scale (usually taken to be the GUT scale) is motivated by general features of supergravity models, it does not carry all of the constraints imposed by minimal supergravity (mSUGRA). In particular, the CMSSM does not impose a relation between the trilinear and bilinear soft supersymmetry breaking terms, B_0 = A_0 - m_0, nor does it impose the relation between the soft scalar masses and the gravitino mass, m_0 = m_{3/2}. As a consequence, tan(\beta) is computed given values of the other CMSSM input parameters. By considering a Giudice-Masiero (GM) extension to mSUGRA, one can introduce new parameters to the K\"ahler potential which are associated with the Higgs sector and recover many of the standard CMSSM predictions. However, depending on the value of A_0, one may have a gravitino or a neutralino dark matter candidate. We also consider the consequences of imposing the universality conditions above the GUT scale. This GM extension provides a natural UV completion for the CMSSM.Comment: 16 pages, 11 figures; added erratum correcting several equations and results in Sec.2, Sec.3 and 4 remain unaffected and conclusions unchange

Observation of the astrophysically important 3+ state in 18Ne via elastic scattering of a radioactive 17F beam from 1H

The 17F(p, γ)18 reaction is important in stellar explosions, but its rate has been uncertain because of an expected 3+ state in 18Ne that has never been conclusively observed. This state would provide a strong l = 0 resonance and, depending on its excitation energy, could dominate the stellar reaction rate. We have observed this missing 3+ state by measuring the 1H(17F, p)17F excitation function with a radioactive 17F beam at the ORNL Holifield Radioactive Ion Beam Facility. We find that the state lies at a center-of-mass energy of Er = 599.8 ± 1.5stat ± 2.0sys keV (Ex = 4523.7 ± 2.9keV) and has a width of Γ = 18 ± 2stat ± 1sys keV

The astrophysically important 3+ state in 18Ne and the 17F(py)18Ne stellar rate

Knowledge of the [Formula Presented] reaction rate is important for understanding stellar explosions, but it was uncertain because the properties of an expected but previously unobserved [Formula Presented] state in [Formula Presented] were not known. This state would provide a strong s-wave resonance for the [Formula Presented] system and, depending on its excitation energy, could dominate the stellar reaction rate at temperatures above 0.2 GK. We have observed this missing [Formula Presented] state by measuring the [Formula Presented] excitation function with a radioactive [Formula Presented] beam at the ORNL Holifield Radioactive Ion Beam Facility (HRIBF). We find that the state lies at a center-of-mass energy of [Formula Presented] keV [Formula Presented] and has a width of [Formula Presented] The measured properties of the resonance are only consistent with a [Formula Presented] assignment

Dynamic Assessment of Baroreflex Control of Heart Rate During Induction of Propofol Anesthesia Using a Point Process Method

In this article, we present a point process method to assess dynamic baroreflex sensitivity (BRS) by estimating the baroreflex gain as focal component of a simplified closed-loop model of the cardiovascular system. Specifically, an inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by linear and bilinear bivariate regressions on both the previous R−R intervals (RR) and blood pressure (BP) beat-to-beat measures. The instantaneous baroreflex gain is estimated as the feedback branch of the loop with a point-process filter, while the RRBP feedforward transfer function representing heart contractility and vasculature effects is simultaneously estimated by a recursive least-squares filter. These two closed-loop gains provide a direct assessment of baroreflex control of heart rate (HR). In addition, the dynamic coherence, cross bispectrum, and their power ratio can also be estimated. All statistical indices provide a valuable quantitative assessment of the interaction between heartbeat dynamics and hemodynamics. To illustrate the application, we have applied the proposed point process model to experimental recordings from 11 healthy subjects in order to monitor cardiovascular regulation under propofol anesthesia. We present quantitative results during transient periods, as well as statistical analyses on steady-state epochs before and after propofol administration. Our findings validate the ability of the algorithm to provide a reliable and fast-tracking assessment of BRS, and show a clear overall reduction in baroreflex gain from the baseline period to the start of propofol anesthesia, confirming that instantaneous evaluation of arterial baroreflex control of HR may yield important implications in clinical practice, particularly during anesthesia and in postoperative care.National Institutes of Health (U.S.) (Grant R01-HL084502)National Institutes of Health (U.S.) (Grant K25-NS05758)National Institutes of Health (U.S.) (Grant DP2- OD006454)National Institutes of Health (U.S.) (Grant T32NS048005)National Institutes of Health (U.S.) (Grant T32NS048005)National Institutes of Health (U.S.) (Grant R01-DA015644)Massachusetts General Hospital (Clinical Research Center, UL1 Grant RR025758

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele