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Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and one-dimensional sliding along the DNA contour is still beneficial in the crowded interior of cells is highly disputed. Here we use a simple model for the bacterial genome inside the cell and present a semi-analytical model for the in vivo target search of transcription factors within the facilitated diffusion framework. Without having to resort to extensive simulations we determine the mean search time of a lac repressor in a living E. coli cell by including parameters deduced from experimental measurements. The results agree very well with experimental findings, and thus the facilitated diffusion picture emerges as a quantitative approach to gene regulation in living bacteria cells. Furthermore we see that the search time is not very sensitive to the parameters characterizing the DNA configuration and that the cell seems to operate very close to optimal conditions for target localization. Local searches as implied by the colocalization mechanism are only found to mildly accelerate the mean search time within our model.
Novel hydrogels based on hydroxyethyl starch modified with polyethylene glycol methacrylate (HES-P(EG)(6)MA) were developed as delivery system for the controlled release of proteins. Since the drug release behavior is supposed to be related to the pore structure of the hydrogel network the pore sizes were determined by cryo-SEM, which is a mild technique for imaging on a nanometer scale. The results showed a decreasing pore size and an increase in pore homogeneity with increasing polymer concentration. Furthermore, the mesh sizes of the hydrogels were calculated based on swelling data. Pore and mesh size were significantly different which indicates that both structures are present in the hydrogel. The resulting structural model was correlated with release data for bulk hydrogel cylinders loaded with FITC-dextran and hydrogel microspheres loaded with FITC-IgG and FITC-dextran of different molecular size. The initial release depended much on the relation between hydrodynamic diameter and pore size while the long term release of the incorporated substances was predominantly controlled by degradation of the network of the much smaller meshes.
Robustness of biochemical systems has become one of the central questions in systems biology although it is notoriously difficult to formally capture its multifaceted nature. Maintenance of normal system function depends not only on the stoichiometry of the underlying interrelated components, but also on the multitude of kinetic parameters. Invariant flux ratios, obtained within flux coupling analysis, as well as invariant complex ratios, derived within chemical reaction network theory, can characterize robust properties of a system at steady state. However, the existing formalisms for the description of these invariants do not provide full characterization as they either only focus on the flux-centric or the concentration-centric view. Here we develop a novel mathematical framework which combines both views and thereby overcomes the limitations of the classical methodologies. Our unified framework will be helpful in analyzing biologically important system properties.
Matrix product states and their continuous analogues are variational classes of states that capture quantum many-body systems or quantum fields with low entanglement; they are at the basis of the density-matrix renormalization group method and continuous variants thereof. In this work we show that, generically, N-point functions of arbitrary operators in discrete and continuous translation invariant matrix product states are completely characterized by the corresponding two- and three-point functions. Aside from having important consequences for the structure of correlations in quantum states with low entanglement, this result provides a new way of reconstructing unknown states from correlation measurements, e. g., for one-dimensional continuous systems of cold atoms. We argue that such a relation of correlation functions may help in devising perturbative approaches to interacting theories.
Gamma-ray line signatures can be expected in the very-high-energy (E-gamma > 100 GeV) domain due to self-annihilation or decay of dark matter (DM) particles in space. Such a signal would be readily distinguishable from astrophysical gamma-ray sources that in most cases produce continuous spectra that span over several orders of magnitude in energy. Using data collected with the H. E. S. S. gamma-ray instrument, upper limits on linelike emission are obtained in the energy range between similar to 500 GeV and similar to 25 TeV for the central part of the Milky Way halo and for extragalactic observations, complementing recent limits obtained with the Fermi-LAT instrument at lower energies. No statistically significant signal could be found. For monochromatic gamma-ray line emission, flux limits of (2 x 10(-7)-2 x 10(-5)) m(-2)s(-1)sr(-1) and (1 x 10(-8)- 2 x 10(-6)) m(-2)s(-1)sr(-1) are obtained for the central part of the Milky Way halo and extragalactic observations, respectively. For a DM particle mass of 1 TeV, limits on the velocity- averaged DM annihilation cross section <sigma upsilon >(chi chi ->gamma gamma) reach similar to 10(-27)cm(3)s(-1), based on the Einasto parametrization of the Galactic DM halo density profile. DOI: 10.1103/PhysRevLett.110.041301
Six-color time-resolved forster resonance energy transfer for ultrasensitive multiplexed biosensing
(2013)
Simultaneous monitoring of multiple molecular interactions and multiplexed detection of several diagnostic biomarkers at very low concentrations have become important issues in advanced biological and chemical sensing. Here we present an optically multiplexed six-color Forster resonance energy transfer (FRET) biosensor for simultaneous monitoring of five different individual binding events. We combined simultaneous FRET from one Tb complex to five different organic dyes measured in a filter-based time-resolved detection format with a sophisticated spectral crosstalk correction, which results in very efficient background suppression. The advantages and robustness of the multiplexed FRET sensor were exemplified by analyzing a 15-component lung cancer immunoassay involving 10 different antibodies and five different tumor markers in a single 50 mu L human serum sample. The multiplexed biosensor offers clinically relevant detection limits in the low picomolar (ng/mL) concentration range for all five markers, thus providing an effective early screening tool for lung cancer with the possibility of distinguishing small-cell from non-small-cell lung carcinoma. This novel technology will open new doors for multiple biomarker diagnostics as well as multiplexed real-time imaging and spectroscopy.
Evidence for an approximate analog system of numbers has been provided by the finding that the comparison of two numerals takes longer and is more error-prone if the semantic distance between the numbers becomes smaller (so-called numerical distance effect). Recent embodied theories suggest that analog number representations are based on previous sensory experiences and constitute therefore a common magnitude metric shared by multiple domains. Here we demonstrate the existence of a cross-modal semantic distance effect between symbolic and tactile numerosities. Participants received tactile stimulations of different amounts of fingers while reading Arabic digits and indicated verbally whether the amount of stimulated fingers was different from the simultaneously presented digit or not. The larger the semantic distance was between the two numerosities, the faster and more accurate participants made their judgments. This cross-modal numerosity distance effect suggests a direct connection between tactile sensations and the concept of numerical magnitude. A second experiment replicated the interaction between symbolic and tactile numerosities and showed that this effect is not modulated by the participants' finger counting habits. Taken together, our data provide novel evidence for a shared metric for symbolic and tactile numerosities as an instance of an embodied representation of numbers.
Management of data to produce scientific knowledge is a key challenge for biological research in the 21st century. Emerging high-throughput technologies allow life science researchers to produce big data at speeds and in amounts that were unthinkable just a few years ago. This places high demands on all aspects of the workflow: from data capture (including the experimental constraints of the experiment), analysis and preservation, to peer-reviewed publication of results. Failure to recognise the issues at each level can lead to serious conflicts and mistakes; research may then be compromised as a result of the publication of non-coherent protocols, or the misinterpretation of published data. In this report, we present the results from a workshop that was organised to create an ontological data-modelling framework for Laboratory Protocol Standards for the Molecular Methods Database (MolMeth). The workshop provided a set of short- and long-term goals for the MolMeth database, the most important being the decision to use the established EXACT description of biomedical ontologies as a starting point.
Block copolymer elastomer conductors (BEC) are mixtures of block copolymers grafted with conducting polymers, which are found to support very large strains, while retaining a high level of conductivity. These novel materials may find use in stretchable electronics. The use of BEC is demonstrated in a capacitive strain sensor and in an artificial muscle of the dielectric elastomer actuator type, supporting more than 100% actuation strain and capacity strain sensitivity up to 300%.
The Acheulean technological tradition, characterized by a large (>10 cm) flake-based component, represents a significant technological advance over the Oldowan. Although stone tool assemblages attributed to the Acheulean have been reported from as early as circa 1.6-1.75 Ma, the characteristics of these earliest occurrences and comparisons with later assemblages have not been reported in detail. Here, we provide a newly established chronometric calibration for the Acheulean assemblages of the Konso Formation, southern Ethiopia, which span the time period similar to 1.75 to <1.0 Ma. The earliest Konso Acheulean is chronologically indistinguishable from the assemblage recently published as the world's earliest with an age of similar to 1.75 Ma at Kokiselei, west of Lake Turkana, Kenya. This Konso assemblage is characterized by a combination of large picks and crude bifaces/unifaces made predominantly on large flake blanks. An increase in the number of flake scars was observed within the Konso Formation handaxe assemblages through time, but this was less so with picks. The Konso evidence suggests that both picks and handaxes were essential components of the Acheulean from its initial stages and that the two probably differed in function. The temporal refinement seen, especially in the handaxe forms at Konso, implies enhanced function through time, perhaps in processing carcasses with long and stable cutting edges. The documentation of the earliest Acheulean at similar to 1.75 Ma in both northern Kenya and southern Ethiopia suggests that behavioral novelties were being established in a regional scale at that time, paralleling the emergence of Homo erectus-like hominid morphology.