Clostridium difficile surface proteins are anchored to the cell wall using CWB2 motifs that recognise the anionic polymer PSII

Gram-positive surface proteins can be covalently or non-covalently anchored to the cell wall and can impart important properties on the bacterium in respect of cell envelope organisation and interaction with the environment. We describe here a mechanism of protein anchoring involving tandem CWB2 motifs found in a large number of cell wall proteins in the Firmicutes. In the Clostridium difficile cell wall protein family, we show the three tandem repeats of the CWB2 motif are essential for correct anchoring to the cell wall. CWB2 repeats are non-identical and cannot substitute for each other, as shown by the secretion into the culture supernatant of proteins containing variations in the patterns of repeats. A conserved Ile Leu Leu sequence within the CWB2 repeats is essential for correct anchoring, although a preceding proline residue is dispensable. We propose a likely genetic locus encoding synthesis of the anionic polymer PSII and, using RNA knock-down of key genes, reveal subtle effects on cell wall composition. We show that the anionic polymer PSII binds two cell wall proteins, SlpA and Cwp2, and these interactions require the CWB2 repeats, defining a new mechanism of protein anchoring in Gram-positive bacteria

Cognitive, behavioural and psychological barriers to the prevention of severe hypoglycaemia: A qualitative study of adults with type 1 diabetes

Objectives: Severe hypoglycaemia affects approximately one in three people with type 1 diabetes and is the most serious side effect of insulin therapy. Our aim was to explore individualistic drivers of severe hypoglycaemia events. Methods: In-depth semi-structured interviews were conducted with a purposive sample of 17 adults with type 1 diabetes and a history of recurrent severe hypoglycaemia, to elicit experiences of hypoglycaemia (symptoms/awareness, progression from mild to severe and strategies for prevention/treatment). Interviews were analysed using an adapted grounded theory approach. Results: Three main themes emerged: hypoglycaemia-induced cognitive impairment, behavioural factors and psychological factors. Despite experiencing early hypoglycaemic symptoms, individuals often delayed intervention due to impaired/distracted attention, inaccurate risk assessment, embarrassment, worry about rebound hyperglycaemia or unavailability of preferred glucose source. Delay coupled with use of a slow-acting glucose source compromised prevention of severe hypoglycaemia. Conclusion: Our qualitative data highlight the multifaceted, idiosyncratic nature of severe hypoglycaemia and confirm that individuals with a history of recurrent severe hypoglycaemia may have specific thought and behaviour risk profiles. Individualised prevention plans are required, emphasising both the need to attend actively to mild hypoglycaemic symptoms and to intervene promptly with an appropriate, patient-preferred glucose source to prevent progression to severe hypoglycaemia

Stringent bounds to spatial variations of the electron-to-proton mass ratio in the Milky Way

The ammonia method to probe variations of the electron-to-proton mass ratio, Delta_mu/mu, is applied for the first time to dense prestellar molecular clouds in the Milky Way. Carefully selected sample of 21 NH_3/CCS pairs observed in the Perseus molecular cloud provide the offset Delta V (CCS-NH_3)= 36+/-7_{stat}+/-13.5_{sys} m/s . A similar offset of Delta V = 40.8 +/- 12.9_{stat} m/s between NH_3 (J,K) = (1,1) and N_2H+ J = 1-0 has been found in an isolated dense core L183 by Pagani et al. (2009). Overall these observations provide a safe bound of a maximum offset between ammonia and the other molecules at the level of Delta V < 100 m/s. This bound corresponds to Delta_mu/mu < 1E-7, which is an order of magnitude more sensitive than available extragalactic constraints. Taken at face value the measured Delta V shows positive shifts between the line centers of NH_3 and these two other molecules and suggest a real offset, which would imply a Delta_mu/mu about 4E-8. If Delta_mu/mu follows the gradient of the local gravitational potential, then the obtained results are in conflict with laboratory atomic clock experiments in the solar system by 5 orders of magnitude, thus requiring a chameleon-type scalar field model. New measurements involving other molecules and a wider range of objects along with verification of molecular rest frequencies are currently planned to confirm these first indications.Comment: 7 pages +2 figures. Galileo Galilei Institute Conferences on Dark Matter and Dark Energ

Dynamic analysis of high static low dynamic stiffness vibration isolation mounts

The high static low dynamic stiffness (HSLDS) concept is a design strategy for an anti-vibration mount that seeks to increase isolation by lowering the natural frequency of the mount, whilst maintaining the same static load bearing capacity. Previous studies have successfully analysed many features of the response by modelling the concept as a Duffing oscillator. This study extends the previous findings by characterising the HSLDS model in terms of two simple parameters. A fifth-order polynomial model allows us to explore the effects of these parameters. We analyse the steady-state response, showing that simple changes to the shape of the force displacement curve can have large effects on the amplitude and frequency of peak response, and can even lead to unbounded response at certain levels of excitation. Harmonics of the fundamental response are also analysed, and it is shown that they are unlikely to pose significant design limitations. Predictions compare well to simulation results

Force-Extension Relations for Polymers with Sliding Links

Topological entanglements in polymers are mimicked by sliding rings (slip-links) which enforce pair contacts between monomers. We study the force-extension curve for linear polymers in which slip-links create additional loops of variable size. For a single loop in a phantom chain, we obtain exact expressions for the average end-to-end separation: The linear response to a small force is related to the properties of the unstressed chain, while for a large force the polymer backbone can be treated as a sequence of Pincus--de Gennes blobs, the constraint effecting only a single blob. Generalizing this picture, scaling arguments are used to include self-avoiding effects.Comment: 4 pages, 5 figures; accepted to Phys. Rev. E (Brief Report

A nonlinear spring mechanism incorporating a bistable composite plate for vibration isolation

The High Static Low Dynamic Stiffness (HSLDS) concept is a design strategy for a nonlinear anti-vibration mount that seeks to increase isolation by lowering the natural frequency of the mount whilst maintaining the same static load bearing capacity. It has previously been proposed that an HSLDS mount could be implemented by connecting linear springs in parallel with the transverse flexure of a composite bistable plate — a plate that has two stable shapes between which it may snap. Using a bistable plate in this way will lead to lightweight and efficient designs of HSLDS mounts. This paper experimentally demonstrates the feasibility of this idea. Firstly, the quasi-static force–displacement curve of a mounted bistable plate is determined experimentally. Then the dynamic response of a nonlinear mass–spring system incorporating this plate is measured. Excellent agreement is obtained when compared to theoretical predictions based on the measured force–displacement curve, and the system shows a greater isolation region and a lower peak response to base excitation than the equivalent linear system

Knots in Charged Polymers

The interplay of topological constraints and Coulomb interactions in static and dynamic properties of charged polymers is investigated by numerical simulations and scaling arguments. In the absence of screening, the long-range interaction localizes irreducible topological constraints into tight molecular knots, while composite constraints are factored and separated. Even when the forces are screened, tight knots may survive as local (or even global) equilibria, as long as the overall rigidity of the polymer is dominated by the Coulomb interactions. As entanglements involving tight knots are not easy to eliminate, their presence greatly influences the relaxation times of the system. In particular, we find that tight knots in open polymers are removed by diffusion along the chain, rather than by opening up. The knot diffusion coefficient actually decreases with its charge density, and for highly charged polymers the knot's position appears frozen.Comment: Revtex4, 9 pages, 9 eps figure

Global Study of Nuclear Structure Functions

We present the results of a phenomenological study of unpolarized nuclear structure functions for a wide kinematical region of x and Q^2. As a basis of our phenomenology we develop a model which takes into account a number of different nuclear effects including nuclear shadowing, Fermi motion and binding, nuclear pion excess and off-shell correction to bound nucleon structure functions. Within this approach we perform a statistical analysis of available data on the ratio of the nuclear structure functions F_2 for different nuclei in the range from the deuteron to the lead. We express the off-shell effect and the effective scattering amplitude describing nuclear shadowing in terms of few parameters which are common to all nuclei and have a clear physical interpretation. The parameters are then extracted from statistical analysis of data. As a result, we obtain an excellent overall agreement between our calculations and data in the entire kinematical region of x and Q^2. We discuss a number of applications of our model which include the calculation of the deuteron structure functions, nuclear valence and sea quark distributions and nuclear structure functions for neutrino charged-current scattering.Comment: 67 pages, 18 figures (v3: updated text and references, a new section with discussion about relation between off-shell effect and modification of the nucleon size in nuclei, accepted for publication in Nucl. Phys. A

Cosmological distance indicators

We review three distance measurement techniques beyond the local universe: (1) gravitational lens time delays, (2) baryon acoustic oscillation (BAO), and (3) HI intensity mapping. We describe the principles and theory behind each method, the ingredients needed for measuring such distances, the current observational results, and future prospects. Time delays from strongly lensed quasars currently provide constraints on $H_0$ with < 4% uncertainty, and with 1% within reach from ongoing surveys and efforts. Recent exciting discoveries of strongly lensed supernovae hold great promise for time-delay cosmography. BAO features have been detected in redshift surveys up to z <~ 0.8 with galaxies and z ~ 2 with Ly-$\alpha$ forest, providing precise distance measurements and $H_0$ with < 2% uncertainty in flat $\Lambda$CDM. Future BAO surveys will probe the distance scale with percent-level precision. HI intensity mapping has great potential to map BAO distances at z ~ 0.8 and beyond with precisions of a few percent. The next years ahead will be exciting as various cosmological probes reach 1% uncertainty in determining $H_0$, to assess the current tension in $H_0$ measurements that could indicate new physics.Comment: Review article accepted for publication in Space Science Reviews (Springer), 45 pages, 10 figures. Chapter of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Ag

Adding tree rings to North America's National Forest Inventories: an essential tool to guide drawdown of atmospheric CO2

Tree-ring time series provide long-term, annually resolved information on the growth of trees. When sampled in a systematic context, tree-ring data can be scaled to estimate the forest carbon capture and storage of landscapes, biomes, and-ultimately-the globe. A systematic effort to sample tree rings in national forest inventories would yield unprecedented temporal and spatial resolution of forest carbon dynamics and help resolve key scientific uncertainties, which we highlight in terms of evidence for forest greening (enhanced growth) versus browning (reduced growth, increased mortality). We describe jump-starting a tree-ring collection across the continent of North America, given the commitments of Canada, the United States, and Mexico to visit forest inventory plots, along with existing legacy collections. Failing to do so would be a missed opportunity to help chart an evidence-based path toward meeting national commitments to reduce net greenhouse gas emissions, urgently needed for climate stabilization and repair.Published versio