Identification of a system required for the functional surface localization of sugar binding proteins with class III signal peptides in Sulfolobus solfataricus

The hyperthermophilic archaeon Sulfolobus solfataricus contains an unusual large number of sugar binding proteins that are synthesized as precursors with a class III signal peptide. Such signal peptides are commonly used to direct archaeal flagellin subunits or bacterial (pseudo)pilins into extracellular macromolecular surface appendages. Likewise, S. solfataricus binding proteins have been suggested to assemble in higher ordered surface structures as well, tentatively termed the bindosome. Here we show that S. solfataricus contains a specific system that is needed for the functional surface localization of sugar binding proteins. This system, encoded by the bas (bindosome assembly system) operon, is composed of five proteins: basABC, three homologues of so-called bacterial (pseudo)pilins; BasE, a cytoplasmic ATPase; and BasF, an integral membrane protein. Deletion of either the three (pseudo)pilin genes or the basEF genes resulted in a severe defect of the cells to grow on substrates which are transported by sugar binding proteins containing class III signal peptides, while growth on glucose and maltose was restored when the corresponding genes were reintroduced in these cells. Concomitantly, ΔbasABC and ΔbasEF cells were severely impaired in glucose uptake even though the sugar binding proteins were normally secreted across the cytoplasmic membrane. These data underline the hypothesis that the bas operon is involved in the functional localization of sugar binding proteins at the cell surface of S. solfataricus. In contrast to surface structure assembly systems of Gram-negative bacteria, the bas operon seems to resemble an ancestral simplified form of these machineries.

Sound radiation from a high speed axial flow fan due to the inlet turbulence quadrupole interaction

A formula is obtained for the total acoustic power spectra radiated out the front of the fan as a function of frequency. The formula involves the design parameters of the fan as well as the statistical properties of the incident turbulence. Numerical results are calculated for values of the parameters in the range of interest for quiet fans tested at the Lewis Research Center. As in the dipole analysis, when the turbulence correlation lengths become equal to the interblade spacing, the predicted spectra exhibit peaks around the blade passing frequency and its harmonics. There has recently been considerable conjecture about whether the stretching of turbulent eddies as they enter a stationary fan could result in the inlet turbulence being the dominant source of pure tones from nontranslating fans. The results of the current analysis show that, unless the turbulent eddies become quite elongated, this noise source contributes predominantly to the broadband spectrum

The Parameter Houlihan: a solution to high-throughput identifiability indeterminacy for brutally ill-posed problems

One way to interject knowledge into clinically impactful forecasting is to use data assimilation, a nonlinear regression that projects data onto a mechanistic physiologic model, instead of a set of functions, such as neural networks. Such regressions have an advantage of being useful with particularly sparse, non-stationary clinical data. However, physiological models are often nonlinear and can have many parameters, leading to potential problems with parameter identifiability, or the ability to find a unique set of parameters that minimize forecasting error. The identifiability problems can be minimized or eliminated by reducing the number of parameters estimated, but reducing the number of estimated parameters also reduces the flexibility of the model and hence increases forecasting error. We propose a method, the parameter Houlihan, that combines traditional machine learning techniques with data assimilation, to select the right set of model parameters to minimize forecasting error while reducing identifiability problems. The method worked well: the data assimilation-based glucose forecasts and estimates for our cohort using the Houlihan-selected parameter sets generally also minimize forecasting errors compared to other parameter selection methods such as by-hand parameter selection. Nevertheless, the forecast with the lowest forecast error does not always accurately represent physiology, but further advancements of the algorithm provide a path for improving physiologic fidelity as well. Our hope is that this methodology represents a first step toward combining machine learning with data assimilation and provides a lower-threshold entry point for using data assimilation with clinical data by helping select the right parameters to estimate

Evidence for a smooth onset of deformation in the neutron-rich Kr isotopes

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMThe neutron-rich nuclei 94,96Kr were studied via projectile Coulomb excitation at the REX-ISOLDE facility at CERN. Level energies of the first excited 2+ states and their absolute E2 transition strengths to the ground state are determined and discussed in the context of the E(21+) and B(E2; 21+ → 01+) systematics of the krypton chain. Contrary to previously published results no sudden onset of deformation is observed. This experimental result is supported by a new proton-neutron interacting boson model calculation based on the constrained Hartree-Fock-Bogoliubov approach using the microscopic Gogny-D1M energy density functionalThis work was supported by the BMBF under Contracts No. 06KY9136 and No. 06MT238, by ENSAR, by the DFG Cluster of Excellence Origin and Structure of the Universe, and by the grant-in-aid for scientific research for JSPS Fellows (Grant No. 217368). One of the authors (J. D.) would like to acknowledge the support of FWO-Vlaanderen (Belgium

Differential regulation of bladder pain and voiding function by sensory afferent populations revealed by selective optogenetic activation

Bladder-innervating primary sensory neurons mediate reflex-driven bladder function under normal conditions, and contribute to debilitating bladder pain and/or overactivity in pathological states. The goal of this study was to examine the respective roles of defined subtypes of afferent neurons in bladder sensation and function in vivo via direct optogenetic activation. To accomplish this goal, we generated transgenic lines that express a Channelrhodopsin-2-eYFP fusion protein (ChR2-eYFP) in two distinct populations of sensory neurons: TRPV1-lineage neurons (Trpv1Cre;Ai32, the majority of nociceptors) and Nav1.8+ neurons (Scn10aCre;Ai32, nociceptors and some mechanosensitive fibers). In spinal cord, eYFP+ fibers in Trpv1Cre;Ai32 mice were observed predominantly in dorsal horn (DH) laminae I-II, while in Scn10aCre;Ai32 mice they extended throughout the DH, including a dense projection to lamina X. Fiber density correlated with number of retrogradely-labeled eYFP+ dorsal root ganglion neurons (82.2% Scn10aCre;Ai32 vs. 62% Trpv1Cre;Ai32) and degree of DH excitatory synaptic transmission. Photostimulation of peripheral afferent terminals significantly increased visceromotor responses to noxious bladder distension (30–50 mmHg) in both transgenic lines, and to non-noxious distension (20 mmHg) in Scn10aCre;Ai32 mice. Depolarization of ChR2+ afferents in Scn10aCre;Ai32 mice produced low- and high-amplitude bladder contractions respectively in 53% and 27% of stimulation trials, and frequency of high-amplitude contractions increased to 60% after engagement of low threshold (LT) mechanoreceptors by bladder filling. In Trpv1Cre;Ai32 mice, low-amplitude contractions occurred in 27% of trials before bladder filling, which was pre-requisite for light-evoked high-amplitude contractions (observed in 53.3% of trials). Potential explanations for these observations include physiological differences in the thresholds of stimulated fibers and their connectivity to spinal circuits

GW correlation effects on plutonium quasiparticle energies: changes in crystal-field splitting

We present results for the electronic structure of plutonium by using a recently developed quasiparticle self-consistent $GW$ method (\qsgw). We consider a paramagnetic solution without spin-orbit interaction as a function of volume for the face-centered cubic (fcc) unit cell. We span unit-cell volumes ranging from 10% greater than the equilibrium volume of the $\delta$ phase to 90 % of the equivalent for the $\alpha$ phase of Pu. The self-consistent $GW$ quasiparticle energies are compared to those obtained within the Local Density Approximation (LDA). The goal of the calculations is to understand systematic trends in the effects of electronic correlations on the quasiparticle energy bands of Pu as a function of the localization of the $f$ orbitals. We show that correlation effects narrow the $f$ bands in two significantly different ways. Besides the expected narrowing of individual $f$ bands (flatter dispersion), we find that an even more significant effect on the $f$ bands is a decrease in the crystal-field splitting of the different bands.Comment: 9 pages, 7 figures, 3 table

Transgenic Mice which Overexpress Neurotrophin-3 (NT-3) and Method of Use

Transgenic mice express increased levels of neurotrophin-3 (NT-3) in epithelium when their ancestors are microinjected with the NT-3 gene. The NT-3 growth factor expressing transgenic mice are useful in the study of neurodegenerative disorders of the brain such as Parkinson\u27s syndrome and Alzheimer\u27s disease, of the spinal cord motor neurons such as amyotrophic lateral sclerosis, and for testing drug candidates for the treatment of these diseases

Transgenic Mice which Overexpress Nerve Growth Factor

Transgenic mice that express increased levels of nerve growth factor (NGF) in the epidermis and other stratified, keratinized epithelium. The nerve growth factor expressing transgenic mice are useful in the study of neurodegenerative disorders of the brain such as Parkinson\u27s syndrome and Alzheimer\u27s disease and for testing for drug candidates for the treatment of these diseases

Hybridized Agile Software Development of Flight Control Team Tools for International Space Station's Payload Operations Integration Center

Ground systems operations at the National Aeronautics and Space Administration's (NASA) Payload Operations and Integration Center (POIC) at Marshall Space Flight Center (MSFC) recently increased via a High Operations Tempo (HOT) initiative, in order to support more science activities with a fourth crew member on the International Space Station (ISS). The Flight Control Team's (FCT) need to support this increasing pace of payload science operations was the impetus for creating a series of new tools. While their need was clear, the full scope and user experience for each tool was not as well-understood, thus establishing a fixed set of initial requirements was not feasible. A hybridized Agile Software Development (ASD) paradigm was created to take advantage of this uncertainty, plan for it, permit the exploration of novel concepts, and also facilitate a rapid and flexible response to inevitably changing requirements. The POIC's hybridized ASD approach places preeminent focus on providing customer value through the delivery of high quality, customer-focused solutions in short timeframes. This has been successfully achieved through creating unprecedented modes of cooperation and collaboration between operations and software development teams, frequent user evaluations of the software with well-defined feedback mechanisms, increased human factors involvement, and a dedication to successful outcomes by the whole of the POIC. Since space science operations and software development are not typically so closely linked, this paper discusses an approach that offers an optimal way to provide an increased return on investment and a faster time-to-completion than traditional software development paradigms, while aiming at delivering high quality products and customer-driven value