The effect of bacteriochlorophyll derivative WST-D and near infrared light on the molecular and fibrillar architecture of the corneal stroma.

A cross-linking technique involving application of Bacteriochlorophyll Derivative WST-11 mixed with dextran (WST-D) to the epithelium-debrided cornea and illumination with Near Infrared (NIR), has been identified as a promising therapy for stiffening pathologically weakened corneas. To investigate its effect on corneal collagen architecture, x-ray scattering and electron microscopy data were collected from paired WST-D/NIR treated and untreated rabbit corneas. The treated eye received 2.5 mg/mL WST-D and was illuminated by a NIR diode laser (755 nm, 10 mW/cm2). An increase in corneal thickness (caused by corneal oedema) occurred at 1-day post-treatment but resolved in the majority of cases within 4 days. The epithelium was fully healed after 6-8 days. X-ray scattering revealed no difference in average collagen interfibrillar spacing, fibril diameter, D-periodicity or intermolecular spacing between treated and untreated specimens. Similarly, electron microscopy images of the anterior and posterior stroma in healed WST-D/NIR corneas and untreated controls revealed no obvious differences in collagen organisation or fibril diameter. As the size and organisation of stromal collagen is closely associated with the optical properties of the cornea, the absence of any large-scale changes following treatment confirms the potential of WST-D/NIR therapy as a means of safely stiffening the cornea.

Accelerating Lattice Quantum Field Theory Calculations via Interpolator Optimization Using Noisy Intermediate-Scale Quantum Computing.

The only known way to study quantum field theories in nonperturbative regimes is using numerical calculations regulated on discrete space-time lattices. Such computations, however, are often faced with exponential signal-to-noise challenges that render key physics studies untenable even with next generation classical computing. Here, a method is presented by which the output of small-scale quantum computations on noisy intermediate-scale quantum era hardware can be used to accelerate larger-scale classical field theory calculations through the construction of optimized interpolating operators. The method is implemented and studied in the context of the 1+1-dimensional Schwinger model, a simple field theory which shares key features with the standard model of nuclear and particle physics.

Nucleon Structure Functions from Operator Product Expansion on the Lattice.

Deep-inelastic scattering, in the laboratory and on the lattice, is most instructive for understanding how the nucleon is built from quarks and gluons. The long-term goal is to compute the associated structure functions from first principles. So far this has been limited to model calculations. In this Letter we propose a new method to compute the structure functions directly from the virtual, all-encompassing Compton amplitude, utilizing the operator product expansion. This overcomes issues of renormalization and operator mixing, which so far have hindered lattice calculations of power corrections and higher moments.

Determination of the strange nucleon form factors.

The strange contribution to the electric and magnetic form factors of the nucleon is determined at a range of discrete values of Q^{2} up to 1.4 GeV^{2}. This is done by combining a recent analysis of lattice QCD results for the electromagnetic form factors of the octet baryons with experimental determinations of those quantities. The most precise result is a small negative value for the strange magnetic moment: G_{M}^{s}(Q^{2}=0)=-0.07±0.03µ_{N}. At larger values of Q^{2} both the electric and magnetic form factors are consistent with zero to within 2 standard deviations.

Octet spin fractions and the proton spin problem.

The relatively small fraction of the spin of the proton carried by its quarks presents a major challenge to our understanding of the strong interaction. Traditional efforts to explore this problem have involved new and imaginative experiments and QCD based studies of the nucleon. We propose a new approach to the problem that exploits recent advances in lattice QCD. In particular, we extract values for the spin carried by the quarks in other members of the baryon octet in order to see whether the suppression observed for the proton is a general property or depends significantly on the baryon structure. We compare these results with the values for the spin fractions calculated within a model that includes the effects of confinement, relativity, gluon exchange currents, and the meson cloud required by chiral symmetry, finding a very satisfactory level of agreement given the precision currently attainable.

Mass of the H dibaryon.

Recent lattice QCD calculations have reported evidence for the existence of a bound state with strangeness -2 and baryon number 2 at quark masses somewhat higher than the physical values. By developing a description of the dependence of this binding energy on the up, down and strange quark masses that allows a controlled chiral extrapolation, we explore the hypothesis that this state is to be identified with the H dibaryon. Taking as input the recent results of the HAL and NPLQCD Collaborations, we show that the H dibaryon is likely to be unbound by 13±14 MeV at the physical point.

Coupling of protein and environment fluctuations.

We review the concepts of protein dynamics developed over the last 35years and extend applications of the unified model of protein dynamics to heat flow and spatial fluctuations in hydrated myoglobin (Mb) powders. Differential scanning calorimetry (DSC) and incoherent neutron scattering (INS) data on hydration Mb powders are explained by the temperature-dependence of the hydration-shell ß(h) process measured by dielectric relaxation spectroscopy (DRS). The unified model explains the temperature dependence of DSC and INS data as a kinetic effect due to a fixed experimental time window and a broad distribution of hydration-shell ß(h) fluctuation rates. We review the slaving of large scale protein motions to the bulk solvent α process, and the metastability of Mb molecules in glass forming bulk solvent at low temperatures. This article is part of a Special Issue entitled: "Protein Dynamics: Experimental and Computational Approaches".

Testing the standard model by precision measurement of the weak charges of quarks.

In a global analysis of the latest parity-violating electron scattering measurements on nuclear targets, we demonstrate a significant improvement in the experimental knowledge of the weak neutral-current lepton-quark interactions at low energy. The precision of this new result, combined with earlier atomic parity-violation measurements, places tight constraints on the size of possible contributions from physics beyond the standard model. Consequently, this result improves the lower-bound on the scale of relevant new physics to approximately 1 TeV.

Extracting nucleon strange and anapole form factors from world data.

The complete world set of parity-violating electron scattering data up to Q2 approximately 0.3 GeV2 is analyzed. We extract the current experimental determination of the strange electric and magnetic form factors of the proton, as well as the weak axial form factors of the proton and neutron, at Q2=0.1 GeV2. Within experimental uncertainties, we find that the strange form factors are consistent with zero, as are the anapole contributions to the axial form factors. Nevertheless, the correlation between the strange and anapole contributions suggest that there is only a small probability that these form factors all vanish simultaneously.

Strange electric form factor of the proton.

By combining the constraints of charge symmetry with new chiral extrapolation techniques and recent low-mass quenched lattice QCD simulations of the individual quark contributions to the electric charge radii of the baryon octet, we obtain an accurate determination of the strange electric charge radius of the proton. While this analysis provides a value for G(E)(s)(Q(2) = 0.1 GeV(2)) in agreement with the best current data, the theoretical error is comparable with that expected from future HAPPEX results from JLab. Together with the earlier determination of G(M)(s), this result considerably constrains the role of hidden flavor in the structure of the nucleon.

Precise determination of the strangeness magnetic moment of the nucleon.

By combining the constraints of charge symmetry with new chiral extrapolation techniques and recent low mass quenched lattice-QCD simulations of the individual quark contributions to the magnetic moments of the nucleon octet, we obtain a precise determination of the strange magnetic moment of the proton. The result, namely, G(s)(M)=(-0.046 +/- 0.019)mu(N) is consistent with the latest experimental measurements but an order of magnitude more precise. This poses a tremendous challenge for future experiments.

Bulk-solvent and hydration-shell fluctuations, similar to alpha- and beta-fluctuations in glasses, control protein motions and functions.

The concept that proteins exist in numerous different conformations or conformational substates, described by an energy landscape, is now accepted, but the dynamics is incompletely explored. We have previously shown that large-scale protein motions, such as the exit of a ligand from the protein interior, follow the dielectric fluctuations in the bulk solvent. Here, we demonstrate, by using mean-square displacements (msd) from Mossbauer and neutron-scattering experiments, that fluctuations in the hydration shell control fast fluctuations in the protein. We call the first type solvent-slaved or alpha-fluctuations and the second type hydration-shell-coupled or beta-fluctuations. Solvent-slaved motions are similar to the alpha-fluctuations in glasses. Their temperature dependence can be approximated by a Vogel-Tammann-Fulcher relation and they are absent in a solid environment. Hydration-shell-coupled fluctuations are similar to the beta-relaxation in glasses. They can be approximated by a Ferry or an Arrhenius relation, are much reduced or absent in dehydrated proteins, and occur in hydrated proteins even if embedded in a solid. They can be responsible for internal processes such as the migration of ligands within myoglobin. The existence of two functionally important fluctuations in proteins, one slaved to bulk motions and the other coupled to hydration-shell fluctuations, implies that the environment can control protein functions through different avenues and that no real protein transition occurs at approximately 200 K. The large number of conformational substates is essential; proteins cannot function without this reservoir of entropy, which resides mainly in the hydration shell.

Physical nucleon properties from lattice QCD.

We investigate various resummations of the chiral expansion and fit to the extremely accurate lattice QCD data for the mass of the nucleon recently obtained by the CP-PACS group. Using a variety of finite-range regulators, we demonstrate a remarkably robust chiral extrapolation of the nucleon mass. The systematic error associated with the chiral extrapolation alone is estimated to be less than 1%.

Effect of added µ-calpain and post-mortem storage on the mechanical properties of bovine single muscle fibres extended to fracture.

The effects of µ-calpain and post-mortem storage on the strength of single muscle fibres were investigated. During the 10 min of incubation at pH 7.5, µ-calpain became evenly distributed throughout the fibre. µ-Calpain-incubation resulted in thinner (P <0.001) Z-lines and reduced (P <0.001) the strength of the fibres compared to controls. These results demonstrate that µ-calpain is capable of mechanically weakening the muscle fibres. Post-mortem storage of meat for 10 days at 2 °C weakened (P <0.001) the muscle fibres compared to 24-h fibres. The presence or absence of Ca(2+) affected fibre stiffness. Fibres incubated at pH 7.5 in 100 µM Ca(2+) were less stiff than fibres incubated in 200 µM EGTA. Breaking stress and strain were not affected by Ca(2+). We hypothesise that Ca(2+) causes conformational changes in some of the load-bearing proteins, which alters their initial resistance to extension, but does not affect the breaking strength of the fibres.

Type II collagen deposition in cruciate ligament precedes osteoarthritis in the guinea pig knee.

OBJECTIVE: To examine the collagens in cruciate ligaments of young Dunkin-Hartley guinea pigs, to determine whether a change in specific collagen types is an early feature of the spontaneous osteoarthritis (OA), which consistently develops in the medial compartment of the knee in this strain. DESIGN: Collagen types I, II, III, IX, and XI were detected by immunofluorescence microscopy in the anterior and posterior cruciate ligaments of animals at 3, 4-5 and 12 weeks of age. Type II collagen in PCL was further analysed by confocal microscopy or biochemical assay after cyanogen bromide digestion, SDS-PAGE and immunoblotting. Interfibrillar proteoglycans were visualized by transmission electron microscopy. RESULTS: Collagen types I and III formed the bulk of fibrous mid-ligament tissue in all animals. Typical cartilage collagens, types II, IX and XI, were identified by immunolabeling where ligaments attached to tibial bone. Type II collagen, normally restricted to the fibrocartilage attachment sites, was also found at separate foci in anterior fiber bundles of the posterior cruciate ligament in 12-week-old animals. Biochemical data confirmed these observations which, together with electron microscopy showing large atypical proteoglycan structures, suggested the deposition of fibrocartilage within the fibrous mid-ligament. CONCLUSIONS: Cruciate ligaments, especially posterior cruciate ligament in Dunkin-Hartley guinea pigs synthesize cartilage-like matrix in mid-ligament prior to the appearance of classical signs of OA.

Chiral symmetry and the intrinsic structure of the nucleon.

Understanding hadron structure within the framework of QCD is an extremely challenging problem. In order to solve it, it is vital that our thinking should be guided by the best available insight. Our purpose here is to explain the model-independent consequences of the approximate chiral symmetry of QCD for two famous results concerning the structure of the nucleon. We show that both the apparent success of the constituent quark model in reproducing the ratio of the proton to neutron magnetic moments and the apparent success of the Foldy term in reproducing the observed charge radius of the neutron are coincidental. That is, a relatively small change of the current quark mass would spoil both results.

Characterization of type XI collagen-glycosaminoglycan interactions.

Using competitive binding experiments, it was found that native type XI collagen binds heparin, heparan sulfate, and dermatan sulfate. However, interactions were not evident with hyaluronic acid, keratan sulfate, or chondroitin sulfate chains over the concentration range studied. Chondrocyte-matrix interactions were investigated using cell attachment to solid phase type XI collagen. Pretreatment of chondrocytes with either heparin or heparinase significantly reduced attachment to type XI collagen. Incubation of denatured and cyanogen bromide-cleaved type XI collagen with radiolabeled heparin identified sites of interaction on the alpha1(XI) and alpha2(XI) chains. NH(2)-terminal sequence data confirmed that the predominant heparin-binding peptide contained the sequence GKPGPRGQRGPTGPRGSRGAR from the alpha1(XI) chain. Using rotary shadowing electron microscopy of native type XI collagen molecules and heparin-bovine serum albumin conjugate, an additional binding site was identified at one end of the triple helical region of the collagen molecule. This coincides with consensus heparin binding motifs present at the amino-terminal ends of both the alpha1(XI) and the alpha2(XI) chains. The contribution of glycosaminoglycan-type XI collagen interactions to cartilage matrix stabilization is discussed.

Immunolocalization of collagen types II and III in single fibrils of human articular cartilage.

Type II and III fibrillar collagens were localized by immunogold electron microscopy in resin sections of human femoral articular cartilage taken from the upper radial zone in specimens from patients with osteoarthritis. Tissue samples stabilized by high-pressure cryofixation were processed by freeze-substitution, either in acetone containing osmium or in methanol without chemical fixatives, before embedding in epoxy or Lowicryl resin, respectively. Ultrastructural preservation was superior with osmium-acetone, although it was not possible to localize collagens by this method. In contrast, in tissue prepared by low-temperature methods without chemical fixation, collagens were successfully localized with mono- or polyclonal antibodies to the helical (Types II and III) and amino-propeptide (Type III procollagen) domains of the molecule. Dual localization using secondary antibodies labeled with 5- or 10-nm gold particles demonstrated the presence of Types II and III collagen associated within single periodic banded fibrils. Collagen fibrils in articular cartilage are understood to be heteropolymers mainly of Types II, IX, and XI collagen. Our observations provide further evidence for the complexity of these assemblies, with the potential for interactions between at least 11 distinct collagen types as well as several noncollagenous components of the extracellular matrix.

Galactosylation of serum IgG and autoantibodies in murine models of autoimmune haemolytic anaemia.

A number of systemic autoimmune diseases are associated with increased levels of the agalactosyl (G0) IgG isoforms that lack a terminal galactose from the CH2 domain oligosaccharide. The current aim was to determine whether the galactosylation of serum IgG is also reduced in a classic antibody-mediated, organ-specific autoimmune condition, and whether the pathogenic autoantibodies are preferentially G0. In two murine forms of autoimmune haemolytic anaemia (AIHA), sera and autoantibodies eluted from erythrocytes were obtained, and the levels of G0 measured using a lectin-binding assay. Serum IgG galactosylation was unaffected following the induction of AIHA in CBA/Igb mice by immunization with rat erythrocytes, but in all animals with the disease the IgG autoantibodies generated were more G0 than the sera. The anti-rat erythrocyte antibodies were similar to the autoantibodies in being preferentially G0, and when CBA/Igb mice were immunized with canine erythrocytes as a control foreign antigen, there was again a bias towards the production of G0 IgG antibodies. In NZB mice with chronic, spontaneous AIHA, the concentration and galactosylation of both serum IgG and autoantibodies were lower than in the induced model, and the ratio of G0 IgG in the serum and erythrocyte eluates varied markedly between different individuals. Our interpretation of these results is that changes in serum IgG or autoantibody galactosylation are not consistent in different models of AIHA, and that production of low galactosyl antibodies can be a feature of a normal immune response.