Transcriptional regulation of protein complexes in yeast

BACKGROUND: Multiprotein complexes play an essential role in many cellular processes. But our knowledge of the mechanism of their formation, regulation and lifetimes is very limited. We investigated transcriptional regulation of protein complexes in yeast using two approaches. First, known regulons, manually curated or identified by genome-wide screens, were mapped onto the components of multiprotein complexes. The complexes comprised manually curated ones and those characterized by high-throughput analyses. Second, putative regulatory sequence motifs were identified in the upstream regions of the genes involved in individual complexes and regulons were predicted on the basis of these motifs. RESULTS: Only a very small fraction of the analyzed complexes (5-6%) have subsets of their components mapping onto known regulons. Likewise, regulatory motifs are detected in only about 8-15% of the complexes, and in those, about half of the components are on average part of predicted regulons. In the manually curated complexes, the so-called 'permanent' assemblies have a larger fraction of their components belonging to putative regulons than 'transient' complexes. For the noisier set of complexes identified by high-throughput screens, valuable insights are obtained into the function and regulation of individual genes. CONCLUSIONS: A small fraction of the known multiprotein complexes in yeast seems to have at least a subset of their components co-regulated on the transcriptional level. Preliminary analysis of the regulatory motifs for these components suggests that the corresponding genes are likely to be co-regulated either together or in smaller subgroups, indicating that transcriptionally regulated modules might exist within complexes

Certainty Closure: Reliable Constraint Reasoning with Incomplete or Erroneous Data

Constraint Programming (CP) has proved an effective paradigm to model and solve difficult combinatorial satisfaction and optimisation problems from disparate domains. Many such problems arising from the commercial world are permeated by data uncertainty. Existing CP approaches that accommodate uncertainty are less suited to uncertainty arising due to incomplete and erroneous data, because they do not build reliable models and solutions guaranteed to address the user's genuine problem as she perceives it. Other fields such as reliable computation offer combinations of models and associated methods to handle these types of uncertain data, but lack an expressive framework characterising the resolution methodology independently of the model. We present a unifying framework that extends the CP formalism in both model and solutions, to tackle ill-defined combinatorial problems with incomplete or erroneous data. The certainty closure framework brings together modelling and solving methodologies from different fields into the CP paradigm to provide reliable and efficient approches for uncertain constraint problems. We demonstrate the applicability of the framework on a case study in network diagnosis. We define resolution forms that give generic templates, and their associated operational semantics, to derive practical solution methods for reliable solutions.Comment: Revised versio

Ground-State Electromagnetic Moments of Calcium Isotopes

High-resolution bunched-beam collinear laser spectroscopy was used to measure the optical hyperfine spectra of the $^{43-51}$Ca isotopes. The ground state magnetic moments of $^{49,51}$Ca and quadrupole moments of $^{47,49,51}$Ca were measured for the first time, and the $^{51}$Ca ground state spin $I=3/2$ was determined in a model-independent way. Our results provide a critical test of modern nuclear theories based on shell-model calculations using phenomenological as well as microscopic interactions. The results for the neutron-rich isotopes are in excellent agreement with predictions using interactions derived from chiral effective field theory including three-nucleon forces, while lighter isotopes illustrate the presence of particle-hole excitations of the $^{40}$Ca core in their ground state.Comment: Accepted as a Rapid Communication in Physical Review

Electronic transport in polycrystalline graphene

Most materials in available macroscopic quantities are polycrystalline. Graphene, a recently discovered two-dimensional form of carbon with strong potential for replacing silicon in future electronics, is no exception. There is growing evidence of the polycrystalline nature of graphene samples obtained using various techniques. Grain boundaries, intrinsic topological defects of polycrystalline materials, are expected to dramatically alter the electronic transport in graphene. Here, we develop a theory of charge carrier transmission through grain boundaries composed of a periodic array of dislocations in graphene based on the momentum conservation principle. Depending on the grain boundary structure we find two distinct transport behaviours - either high transparency, or perfect reflection of charge carriers over remarkably large energy ranges. First-principles quantum transport calculations are used to verify and further investigate this striking behaviour. Our study sheds light on the transport properties of large-area graphene samples. Furthermore, purposeful engineering of periodic grain boundaries with tunable transport gaps would allow for controlling charge currents without the need of introducing bulk band gaps in otherwise semimetallic graphene. The proposed approach can be regarded as a means towards building practical graphene electronics.Comment: accepted in Nature Material

Dipole polarizability of 120Sn and nuclear energy density functionals

The electric dipole strength distribution in 120Sn between 5 and 22 MeV has been determined at RCNP Osaka from a polarization transfer analysis of proton inelastic scattering at E_0 = 295 MeV and forward angles including 0{\deg}. Combined with photoabsorption data an electric dipole polarizability \alpha_D(120Sn) = 8.93(36) fm^3 is extracted. The dipole polarizability as isovector observable par excellence carries direct information on the nuclear symmetry energy and its density dependence. The correlation of the new value with the well established \alpha_D(208Pb) serves as a test of its prediction by nuclear energy density functionals (EDFs). Models based on modern Skyrme interactions describe the data fairly well while most calculations based on relativistic Hamiltonians cannot.Comment: 6 pages, 4 figure

Low-energy electric dipole response in 120Sn

The electric dipole strength in 120Sn has been extracted from proton inelastic scattering experiments at E_p = 295 MeV and at forward angles including 0 degree. Below neutron threshoild it differs from the results of a 120Sn(gamma,gamma') experiment and peaks at an excitation energy of 8.3 MeV. The total strength corresponds to 2.3(2)% of the energy-weighted sum rule and is more than three times larger than what is observed with the (gamma,gamma') reaction. This implies a strong fragmentation of the E1 strength and/or small ground state branching ratios of the excited 1- states.Comment: 7 pages, 6 figure

Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries

IMPORTANCE: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS:The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES:Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES: The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS: Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE: Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS

Beyond the neutron drip line: The unbound oxygen isotopes (25)O and (26)O

This is the publisher's version, and is also available electronically from http://journals.aps.org/prc/abstract/10.1103/PhysRevC.88.034313.The very neutron-rich oxygen isotopes 25O and 26O are investigated experimentally and theoretically. The unbound states are populated in an experiment performed at the R3B-LAND setup at GSI via proton-knockout reactions from 26F and 27F at relativistic energies around 442 and 414 MeV/nucleon, respectively. From the kinematically complete measurement of the decay into 24O plus one or two neutrons, the 25O ground-state energy and width are determined, and upper limits for the 26O ground-state energy and lifetime are extracted. In addition, the results provide indications for an excited state in 26O at around 4 MeV. The experimental findings are compared to theoretical shell-model calculations based on chiral two- and three-nucleon (3N) forces, including for the first time residual 3N forces, which are shown to be amplified as valence neutrons are added

MINE: Module Identification in Networks

<p>Abstract</p> <p>Background</p> <p>Graphical models of network associations are useful for both visualizing and integrating multiple types of association data. Identifying modules, or groups of functionally related gene products, is an important challenge in analyzing biological networks. However, existing tools to identify modules are insufficient when applied to dense networks of experimentally derived interaction data. To address this problem, we have developed an agglomerative clustering method that is able to identify highly modular sets of gene products within highly interconnected molecular interaction networks.</p> <p>Results</p> <p>MINE outperforms MCODE, CFinder, NEMO, SPICi, and MCL in identifying non-exclusive, high modularity clusters when applied to the <it>C. elegans </it>protein-protein interaction network. The algorithm generally achieves superior geometric accuracy and modularity for annotated functional categories. In comparison with the most closely related algorithm, MCODE, the top clusters identified by MINE are consistently of higher density and MINE is less likely to designate overlapping modules as a single unit. MINE offers a high level of granularity with a small number of adjustable parameters, enabling users to fine-tune cluster results for input networks with differing topological properties.</p> <p>Conclusions</p> <p>MINE was created in response to the challenge of discovering high quality modules of gene products within highly interconnected biological networks. The algorithm allows a high degree of flexibility and user-customisation of results with few adjustable parameters. MINE outperforms several popular clustering algorithms in identifying modules with high modularity and obtains good overall recall and precision of functional annotations in protein-protein interaction networks from both <it>S. cerevisiae </it>and <it>C. elegans</it>.</p

Electric dipole polarizability of 40^{40}Ca

The electric dipole strength distribution in $^{40}$Ca between 5 and 25 MeV has been determined at RCNP, Osaka, from proton inelastic scattering experiments at very forward angles. Combined with total photoabsorption data at higher excitation energy, this enables an extraction of the electric dipole polarizability $\alpha_\mathrm{D}$($^{40}$Ca) = 1.92(17) fm$^3$. Together with the measured $\alpha_{\rm D}$ in $^{48}$Ca, it provides a stringent test of modern theoretical approaches, including coupled cluster calculations with chiral effective field theory interactions and state-of-the art energy density functionals. The emerging picture is that for this medium-mass region dipole polarizabilities are well described theoretically, with important constraints for the neutron skin in $^{48}$Ca and related equation of state quantities.Comment: 6 pages, 3 figure