Diverse functions for different forms of nuclear actin

In addition to its essential roles as part of the cytoskeleton, actin has also been linked to many processes in the nucleus. Recent data has demonstrated the presence of both monomeric and polymeric actin in the nucleus, and implied distinct functional roles for these actin pools. Monomeric actin seems to be involved in regulation of gene expression through transcription factors, chromatin regulating complexes and RNA polymerases. In addition to cytoplasmic actin regulators, nuclear proteins, such as emerin, can regulate actin polymerization properties specifically in this compartment. Besides of structural roles, nuclear actin filaments may be required for organizing the nuclear contents and for the maintenance of genomic integrity.Peer reviewe

Quantum circuits with uniformly controlled one-qubit gates

Uniformly controlled one-qubit gates are quantum gates which can be represented as direct sums of two-dimensional unitary operators acting on a single qubit. We present a quantum gate array which implements any n-qubit gate of this type using at most 2^{n-1} - 1 controlled-NOT gates, 2^{n-1} one-qubit gates and a single diagonal n-qubit gate. The circuit is based on the so-called quantum multiplexor, for which we provide a modified construction. We illustrate the versatility of these gates by applying them to the decomposition of a general n-qubit gate and a local state preparation procedure. Moreover, we study their implementation using only nearest-neighbor gates. We give upper bounds for the one-qubit and controlled-NOT gate counts for all the aforementioned applications. In all four cases, the proposed circuit topologies either improve on or achieve the previously reported upper bounds for the gate counts. Thus, they provide the most efficient method for general gate decompositions currently known.Comment: 8 pages, 10 figures. v2 has simpler notation and sharpens some result

Using a moving measurement platform for determining the chemical composition of atmospheric aerosols between Moscow and Vladivostok

The TROICA-9 expedition (Trans-Siberian Observations Into the Chemistry of the Atmosphere) was carried out at the Trans-Siberian railway between Moscow and Vladivostok in October 2005. Measurements of aerosol physical and chemical properties were made from an observatory carriage connected to a passenger train. Black carbon (BC) concentrations in fine particles (PM<sub>2.5</sub>, aerodynamic diameter <2.5 μm) were measured with an aethalometer using a five-minute time resolution. Concentrations of inorganic ions and some organic compounds (Cl<sup>−</sup>, NO<sub>3</sub><sup>−</sup>, SO<sub>4</sub><sup>2−</sup>, Na<sup>+</sup>, NH<sub>4</sub><sup>+</sup>, K<sup>+</sup>, Ca<sup>2+</sup>, Mg<sup>2+</sup>, oxalate and methane sulphonate) were measured continuously by using an on-line system with a 15-min time resolution. In addition, particle volume size distributions were determined for particles in the diameter range 3–850 nm using a 10-min time resolution. The continuous measurements were completed with 24-h PM<sub>2.5</sub> filter samples stored in a refrigerator and analyzed later in a chemical laboratory. The analyses included the mass concentrations of PM<sub>2.5</sub>, ions, monosaccharide anhydrides (levoglucosan, galactosan and mannosan) and trace elements (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sb, V and Zn). The mass concentrations of PM<sub>2.5</sub> varied in the range of 4.3–34.8 μg m<sup>−3</sup> with an average of 21.6 μg m<sup>−3</sup>. Fine particle mass consisted mainly of BC (average 27.6%), SO<sub>4</sub><sup>2−</sup> (13.0%), NH<sub>4</sub><sup>+</sup> (4.1%) and NO<sub>3</sub><sup>−</sup> (1.4%). One of the major constituents was obviously organic carbon which was not determined. The contribution of BC was high compared with other studies made in Europe and Asia. High concentrations of ions, BC and particle volume were observed between Moscow and roughly 4000 km east of it, as well as close to Vladivostok, primarily due to local anthropogenic sources. In the natural background area between 4000 and 7200 km away from Moscow, observed concentrations were low, even though local particle sources, such as forest fires, occasionally increased concentrations. During the measured forest fire episodes, most of the aerosol mass appeared to consist of organic particulate matter. Concentrations of the biomass burning tracers levoglucosan, oxalate and potassium were elevated close to the forest fire areas observed by the MODIS satellite. The polluted air masses from Asia seem to have significant influences on the concentration levels of fine particles over south-eastern Russia

Chemical composition of atmospheric aerosols between Moscow and Vladivostok

International audienceThe TROICA-9 expedition (Trans-Siberian Observations Into the Chemistry of the Atmosphere) was carried out at the Trans-Siberian railway between Moscow and Vladivostok in October 2005. Measurements of aerosol physical and chemical properties were made from an observatory carriage connected to a passenger train. Black carbon (BC) concentrations in fine particles (PM2.5, aerodynamic diameter ?, NO3?, SO42?, Na+, NH4+, K+, Ca2+, Mg2+, oxalate and methane sulphonate) were measured continuously by using an on-line system with a 15-min time resolution. In addition, particle volume size distributions were determined for particles in the diameter range 3?850 nm using a 10-min. time resolution. The continuous measurements were completed with 24-h. PM2.5 filter samples which were stored in a refrigerator and later analyzed in chemical laboratory. The analyses included mass concentrations of PM2.5, ions, monosaccharide anhydrides (levoglucosan, galactosan and mannosan) and trace elements (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sb, V and Zn). The mass concentrations of PM2.5 varied in the range of 4.3?34.8 ?g m?3 with an average of 21.6 ?g m?3. Fine particle mass consisted mainly of BC (average 27.6%), SO42? (13.0%), NH4+ (4.1%), and NO3? (1.4%). One of the major constituents was obviously also organic carbon which was not determined. The contribution of BC was high compared with other studies made in Europe and Asia. High concentrations of ions, BC and particle volume were observed between Moscow and roughly 4000 km east of it, as well as close to Vladivostok, primarily due to local anthropogenic sources. In the natural background area between 4000 and 7200 km distance from Moscow, observed concentrations were low, even though there were local particle sources, such as forest fires, that increased occasionally concentrations. The measurements indicated that during forest fire episodes, most of the aerosol mass consisted of organic particulate matter. Concentrations of biomass burning tracers levoglucosan, oxalate and potassium were elevated close to the forest fire areas observed by the MODIS satellite. The polluted air masses from Asia seem to have significant influences on the concentration levels of fine particles over south-eastern Russia

Optogenetic regulation of endogenous proteins

Techniques of protein regulation, such as conditional gene expression, RNA interference, knock-in and knock-out, lack sufficient spatiotemporal accuracy, while optogenetic tools suffer from non-physiological response due to overexpression artifacts. Here we present a near-infrared light-activatable optogenetic system, which combines the specificity and orthogonality of intrabodies with the spatiotemporal precision of optogenetics. We engineer optically-controlled intrabodies to regulate genomically expressed protein targets and validate the possibility to further multiplex protein regulation via dual-wavelength optogenetic control. We apply this system to regulate cytoskeletal and enzymatic functions of two non-tagged endogenous proteins, actin and RAS GTPase, involved in complex functional networks sensitive to perturbations. The optogenetically-enhanced intrabodies allow fast and reversible regulation of both proteins, as well as simultaneous monitoring of RAS signaling with visible-light biosensors, enabling all-optical approach. Growing number of intrabodies should make their incorporation into optogenetic tools the versatile technology to regulate endogenous targets. Optogenetic approaches to control protein-protein interactions usually require overexpression of the target proteins. Here the authors integrate intrabodies into near-infrared- and blue-light activatable optogenetic tools to control endogenous proteins in mammalian cells.Peer reviewe

An EMG-Assisted Muscle-Force Driven Finite Element Analysis Pipeline to Investigate Joint- and Tissue-Level Mechanical Responses in Functional Activities : Towards a Rapid Assessment Toolbox

Publisher Copyright: © 1964-2012 IEEE.Joint tissue mechanics (e.g., stress and strain) are believed to have a major involvement in the onset and progression of musculoskeletal disorders, e.g., knee osteoarthritis (KOA). Accordingly, considerable efforts have been made to develop musculoskeletal finite element (MS-FE) models to estimate highly detailed tissue mechanics that predict cartilage degeneration. However, creating such models is time-consuming and requires advanced expertise. This limits these complex, yet promising, MS-FE models to research applications with few participants and makes the models impractical for clinical assessments. Also, these previously developed MS-FE models have not been used to assess activities other than gait. This study introduces and verifies a semi-automated rapid state-of-the-art MS-FE modeling and simulation toolbox incorporating an electromyography- (EMG) assisted MS model and a muscle-force driven FE model of the knee with fibril-reinforced poro(visco)elastic cartilages and menisci. To showcase the usability of the pipeline, we estimated joint- and tissue-level knee mechanics in 15 KOA individuals performing different daily activities. The pipeline was verified by comparing the estimated muscle activations and joint mechanics to existing experimental data. To determine the importance of the EMG-assisted MS analysis approach, results were compared to those from the same FE models but driven by static-optimization-based MS models. The EMG-assisted MS-FE pipeline bore a closer resemblance to experiments compared to the static-optimization-based MS-FE pipeline. Importantly, the developed pipeline showed great potential as a rapid MS-FE analysis toolbox to investigate multiscale knee mechanics during different activities of individuals with KOA.Peer reviewe

Health-related quality of life change in patients treated at a multidisciplinary pain clinic

Background Multidisciplinary pain management (MPM) is a generally accepted method for treating chronic pain, but heterogeneous outcome measures provide only limited conclusions concerning its effectiveness. Therefore, further studies on the effectiveness of MPM are needed to identify subgroups of patients who benefit, or do not benefit, from these interventions. Our aim was to analyse health-related quality of life (HRQoL) changes after MPM and to identify factors associated with treatment outcomes. Methods We carried out a real world observational follow-up study of chronic pain patients referred to a tertiary multidisciplinary outpatient pain clinic to describe, using the validated HRQoL instrument 15D, the HRQoL change after MPM and to identify factors associated with this change. 1,043 patients responded to the 15D HRQoL questionnaire at baseline and 12 months after the start of treatment. Background data were collected from the pre-admission questionnaire of the pain clinic. Results Fifty-three percent of the patients reported a clinically important improvement and, of these, 81% had a major improvement. Thirty-five percent reported a clinically important deterioration, and 12% had no change in HRQoL. Binary logistic regression analysis revealed that major improvement was positively associated with shorter duration of pain (Peer reviewe

High-speed fixed-target serial virus crystallography

We report a method for serial X-ray crystallography at X-ray free-electron lasers (XFELs), which allows for full use of the current 120-Hz repetition rate of the Linear Coherent Light Source (LCLS). Using a micropatterned silicon chip in combination with the high-speed Roadrunner goniometer for sample delivery, we were able to determine the crystal structures of the picornavirus bovine enterovirus 2 (BEV2) and the cytoplasmic polyhedrosis virus type 18 polyhedrin, with total data collection times of less than 14 and 10 min, respectively. Our method requires only micrograms of sample and should therefore broaden the applicability of serial femtosecond crystallography to challenging projects for which only limited sample amounts are available. By synchronizing the sample exchange to the XFEL repetition rate, our method allows for most efficient use of the limited beam time available at XFELs and should enable a substantial increase in sample throughput at these facilities

Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium

Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively