Assembly and force measurement with SPM-like probes in holographic optical tweezers

We report a high fidelity tomographic reconstruction of the quantum state of photon pairs generated by parametric down-conversion with orbital angular momentum (OAM) entanglement. Our tomography method allows us to estimate an upper and lower bound for the entanglement between the down-converted photons. We investigate the two-dimensional state subspace defined by the OAM states ±ℓ and superpositions thereof, with ℓ=1, 2, ..., 30. We find that the reconstructed density matrix, even for OAMs up to around ℓ=20, is close to that of a maximally entangled Bell state with a fidelity in the range between F=0.979 and F=0.814. This demonstrates that, although the single count-rate diminishes with increasing ℓ, entanglement persists in a large dimensional state space

Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots

A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17 134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cystein slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations.Comment: 40 pages, 13 PostScript figure

Tuning hardness in calcite by incorporation of amino acids

Structural biominerals are inorganic/organic composites that exhibit remarkable mechanical properties. However, the structure–property relationships of even the simplest building unit—mineral single crystals containing embedded macromolecules—remain poorly understood. Here, by means of a model biomineral made from calcite single crystals containing glycine (0–7 mol%) or aspartic acid (0–4 mol%), we elucidate the origin of the superior hardness of biogenic calcite. We analysed lattice distortions in these model crystals by using X-ray diffraction and molecular dynamics simulations, and by means of solid-state nuclear magnetic resonance show that the amino acids are incorporated as individual molecules. We also demonstrate that nanoindentation hardness increased with amino acid content, reaching values equivalent to their biogenic counterparts. A dislocation pinning model reveals that the enhanced hardness is determined by the force required to cut covalent bonds in the molecules

Common Features at the Start of the Neurodegeneration Cascade

A single-molecule study reveals that neurotoxic proteins share common structural features that may trigger neurodegeneration, thus identifying new targets for therapy and diagnosis

Reducing the health disparities of Indigenous Australians: time to change focus

Background: Indigenous peoples have worse health than non-Indigenous, are over-represented amongst the poor and disadvantaged, have lower life expectancies, and success in improving disparities is limited. To address this, research usually focuses on disadvantaged and marginalised groups, offering only partial understanding of influences underpinning slow progress. Critical analysis is also required of those with the power to perpetuate or improve health inequities. In this paper, using Australia as a case example, we explore the effects of ‘White’, Anglo-Australian cultural dominance in health service delivery to Indigenous Australians. We address the issue using race as an organising principle, underpinned by relations of power.Methods: Interviews with non-Indigenous medical practitioners in Western Australia with extensive experience in Indigenous health encouraged reflection and articulation of their insights into factors promoting or impeding quality health care to Indigenous Australians. Interviews were audio-taped and transcribed. An inductive, exploratory analysis identified key themes that were reviewed and interrogated in light of existing literature on health care to Indigenous people, race and disadvantage. The researchers’ past experience, knowledge and understanding of health care and Indigenous health assisted with data interpretation. Informal discussions were also held with colleagues working professionally in Indigenous policy, practice and community settings.Results: Racism emerged as a key issue, leading us to more deeply interrogate the role ‘Whiteness’ plays in Indigenous health care. While Whiteness can refer to skin colour, it also represents a racialized social structure where Indigenous knowledge, beliefs and values are subjugated to the dominant western biomedical model in policy and practice. Racism towards Indigenous patients in health services was institutional and interpersonal. Internalised racism was manifest when Indigenous patients incorporated racist attitudes and beliefs into their lived experience, lowering expectations and their sense of self-worth.Conclusions: Current health policies and practices favour standardised care where the voice of those who are marginalised is often absent. Examining the effectiveness of such models in reducing health disparities requires health providers to critically reflect on whether policies and practices promote or compromise Indigenous health and wellbeing - an important step in changing the discourse that places Indigenous people at the centre of the problem

Rapid internal contraction boosts DNA friction

Macroscopic objects are usually manipulated by force and observed with light. On the nanoscale, however, this is often done oppositely: individual macromolecules are manipulated by light and monitored with force. This procedure, which is the basis of single-molecule force spectroscopy, has led to much of our quantitative understanding of how DNA works, and is now routinely applied to explore molecular structure and interactions, DNA–protein reactions and protein folding. Here we develop the technique further by introducing a dynamic force spectroscopy set-up for a non-invasive inspection of the tension dynamics in a taut strand of DNA. The internal contraction after a sudden release of the molecule is shown to give rise to a drastically enhanced viscous friction, as revealed by the slow relaxation of an attached colloidal tracer. Our systematic theory explains the data quantitatively and provides a powerful tool for the rational design of new dynamic force spectroscopy assays

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Upon impact: the fate of adhering <i>Pseudomonas fluorescens</i> cells during Nanofiltration

Nanofiltration (NF) is a high-pressure membrane filtration process increasingly applied in drinking water treatment and water reuse processes. NF typically rejects divalent salts, organic matter, and micropollutants. However, the efficiency of NF is adversely affected by membrane biofouling, during which microorganisms adhere to the membrane and proliferate to create a biofilm. Here we show that adhered Pseudomonas fluorescens cells under high permeate flux conditions are met with high fluid shear and convective fluxes at the membrane-liquid interface, resulting in their structural damage and collapse. These results were confirmed by fluorescent staining, flow cytometry, and scanning electron microscopy. This present study offers a 'first-glimpse' of cell damage and death during the initial phases of bacterial adhesion to NF membranes and raises a key question about the role of this observed phenomena during early-stage biofilm formation under permeate flux and cross-flow conditions.European Research Council (ERC

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access