Surface effects in multiband superconductors. Application to MgB2_2

Metals with many bands at the Fermi level can have different band dependent gaps in the superconducting state. The absence of translational symmetry at an interface can induce interband scattering and modify the superconducting properties. We dicuss the relevance of these effects to recent experiments in MgB$_2$

Phenotypic lentivirus screens to identify functional single domain antibodies

Manipulation of proteins is key in assessing their in vivo function. Although genetic ablation is straightforward, reversible and specific perturbation of protein function remains a challenge. Single domain antibody fragments, such as camelid-derived VHHs, can serve as inhibitors or activators of intracellular protein function, but functional testing of identified VHHs is laborious. To address this challenge, we have developed a lentiviral screening approach to identify VHHs that elicit a phenotype when expressed intracellularly. We identified 19 antiviral VHHs that protect human A549 cells from lethal infection with influenza A virus (IAV) or vesicular stomatitis virus (VSV), respectively. Both negative-sense RNA viruses are vulnerable to VHHs uniquely specific for their respective nucleoproteins. Antiviral VHHs prevented nuclear import of viral ribonucleoproteins or mRNA transcription, respectively, and may provide clues for novel antiviral reagents. In principle, the screening approach described here should be applicable to identify inhibitors of any pathogen or biological pathway. To identify the proteins essential to a biological pathway, small-molecule inhibitors or activators may be used to manipulate protein function transiently. Alternatively, screens involving mutagenesis, a reduction in levels or complete elimination of gene products are common. As applied to mammalian cells, these methods usually seek to achieve the removal of a protein from its normal biological context. Many proteins are multifunctional, or are components of multi-subunit complexes. Depletion of any single component may cause unexpected phenotypes due to the collapse of entire protein complexes. Small-molecule inhibitors often lack specificity and at best can target a fraction of all the proteins of interest. The screening of chemically diverse libraries must be paired with sophisticated methods to identify the molecular targets of any hit identified. Antibodies have been used as intracellular perturbants of protein function after microinjection or cytosolic expression of single-chain variable antibody fragments, but technical challenges have limited their application to few selected cases. In addition to conventional antibodies, the immune system of camelids generates heavy-chain-only antibodies. Their antigen binding site only consists of the variable domain of the heavy chain. This domain can be expressed on its own and is referred to as a VHH or nanobody, an entity that can retain its function in the reducing environment of the cytosol, independent of glycosylation. Many VHHs bind to their targets with affinities comparable to conventional antibodies. VHHs expressed in the cytosol can therefore act as molecular perturbants by occluding the interfaces involved in protein–protein interactions, by binding in the active sites of enzymes, or through the recognition or stabilization of distinct conformations of their targets. Both phage and yeast display, as well as mass spectrometry in combination with high-throughput sequencing, allow the identification of VHHs based on their binding properties. However, the identification of inhibitory VHHs remains a time-consuming process. VHHs obtained through biochemical screening methods must be expressed individually in the relevant cell type to test for the functional consequences of VHH expression. To address this challenge, we developed a phenotypic VHH screening method in living cells.National Institutes of Health (U.S.) (Health Pioneer Award

A comparison of the ability of the National Early Warning Score and the National Early Warning Score 2 to identify patients at risk of in-hospital mortality: A multi-centre database study.

AIMS: To compare the ability of the National Early Warning Score (NEWS) and the National Early Warning Score 2 (NEWS2) to identify patients at risk of in-hospital mortality and other adverse outcomes. METHODS: We undertook a multi-centre retrospective observational study at five acute hospitals from two UK NHS Trusts. Data were obtained from completed adult admissions who were not fit enough to be discharged alive on the day of admission. Diagnostic coding and oxygen prescriptions were used to identify patients with type II respiratory failure (T2RF). The primary outcome was in-hospital mortality within 24 h of a vital signs observation. Secondary outcomes included unanticipated intensive care unit admission or cardiac arrest within 24 h of a vital signs observation. Discrimination was assessed using the c-statistic. RESULTS: Among 251,266 adult admissions, 48,898 were identified to be at risk of T2RF by diagnostic coding. In this group, NEWS2 showed statistically significant lower discrimination (c-statistic, 95% CI) for identifying in-hospital mortality within 24 h (0.860, 0.857-0.864) than NEWS (0.881, 0.878-0.884). For 1394 admissions with documented T2RF, discrimination was similar for both systems: NEWS2 (0.841, 0.827-0.855), NEWS (0.862, 0.848-0.875). For all secondary endpoints, NEWS2 showed no improvements in discrimination. CONCLUSIONS: NEWS2 modifications to NEWS do not improve discrimination of adverse outcomes in patients with documented T2RF and decrease discrimination in patients at risk of T2RF. Further evaluation of the relationship between SpO2 values, oxygen therapy and risk should be investigated further before wide-scale adoption of NEWS2

Dyson-Schwinger Equations - aspects of the pion

The contemporary use of Dyson-Schwinger equations in hadronic physics is exemplified via applications to the calculation of pseudoscalar meson masses, and inclusive deep inelastic scattering with a determination of the pion's valence-quark distribution function.Comment: 4 pages. Contribution to the Proceedings of ``DPF 2000,'' the Meeting of the Division of Particles and Fields of the American Physical Society, August 9-12, 2000, Department of Physics, the Ohio State University, Columbus, Ohi

Nuclear Resonance Vibrational Spectroscopy of Iron Sulfur Proteins

Nuclear inelastic scattering in conjunction with density functional theory (DFT) calculations has been applied for the identification of vibrational modes of the high-spin ferric and the high-spin ferrous iron-sulfur center of a rubredoxin-type protein from the thermophylic bacterium Pyrococcus abysii

Could Large CP Violation Be Detected at Colliders?

We argue that CP--violation effects below a few tenths of a percent are probably undetectable at hadron and electron colliders. Thus only operators whose contributions interfere with tree--level Standard Model amplitudes are detectable. We list these operators for Standard Model external particles and some two and three body final state reactions that could show detectable effects. These could test electroweak baryogenesis scenarios.Comment: 11pp, LaTeX, UM--TH--92--27(massaged to make TeX output cleaner), no picture

Jamming coverage in competitive random sequential adsorption of binary mixture

We propose a generalized car parking problem where cars of two different sizes are sequentially parked on a line with a given probability $q$. The free parameter $q$ interpolates between the classical car parking problem of only one car size and the competitive random sequential adsorption (CRSA) of a binary mixture. We give an exact solution to the CRSA rate equations and find that the final coverage, the jamming limit, of the line is always larger for a binary mixture than for the uni-sized case. The analytical results are in good agreement with our direct numerical simulations of the problem.Comment: 4 pages 2-column RevTeX, Four figures, (there was an error in the previous version. We replaced it (including figures) with corrected and improved version that lead to new results and conclusions

Short time evolved wave functions for solving quantum many-body problems

The exact ground state of a strongly interacting quantum many-body system can be obtained by evolving a trial state with finite overlap with the ground state to infinite imaginary time. In this work, we use a newly discovered fourth order positive factorization scheme which requires knowing both the potential and its gradients. We show that the resultaing fourth order wave function alone, without further iterations, gives an excellent description of strongly interacting quantum systems such as liquid 4He, comparable to the best variational results in the literature.Comment: 5 pages, 3 figures, 1 tabl