Protective Effects of Non-Anticoagulant Activated Protein C Variant (D36A/L38D/A39V) in a Murine Model of Ischaemic Stroke

Ischaemic stroke is caused by occlusive thrombi in the cerebral vasculature. Although tissue-plasminogen activator (tPA) can be administered as thrombolytic therapy, it has major limitations, which include disruption of the blood-brain barrier and an increased risk of bleeding. Treatments that prevent or limit such deleterious effects could be of major clinical importance. Activated protein C (APC) is a natural anticoagulant that regulates thrombin generation, but also confers endothelial cytoprotective effects and improved endothelial barrier function mediated through its cell signalling properties. In murine models of stroke, although APC can limit the deleterious effects of tPA due to its cell signalling function, its anticoagulant actions can further elevate the risk of bleeding. Thus, APC variants such as APC(5A), APC(Ca-ins) and APC(36-39) with reduced anticoagulant, but normal signalling function may have therapeutic benefit. Human and murine protein C (5A), (Ca-ins) and (36-39) variants were expressed and characterised. All protein C variants were secreted normally, but 5-20% of the protein C (Ca-ins) variants were secreted as disulphide-linked dimers. Thrombin generation assays suggested reductions in anticoagulant function of 50- to 57-fold for APC(36-39), 22- to 27-fold for APC(Ca-ins) and 14- to 17-fold for APC(5A). Interestingly, whereas human wt APC, APC(36-39) and APC(Ca-ins) were inhibited similarly by protein C inhibitor (t½ - 33 to 39 mins), APC(5A) was inactivated ~9-fold faster (t½ - 4 mins). Using the murine middle cerebral artery occlusion ischaemia/repurfusion injury model, in combination with tPA, APC(36-39), which cannot be enhanced by its cofactor protein S, significantly improved neurological scores, reduced cerebral infarct area by ~50% and reduced oedema ratio. APC(36-39) also significantly reduced bleeding in the brain induced by administration of tPA, whereas wt APC did not. If our data can be extrapolated to clinical settings, then APC(36-39) could represent a feasible adjunctive therapy for ischaemic stroke

Introduction to the "Scoliosis" Journal Brace Technology Thematic Series: increasing existing knowledge and promoting future developments

Bracing is the main non-surgical intervention in the treatment of idiopathic scoliosis during growth, in hyperkyphosis (and Scheuermann disease) and occasionally for spondylolisthesis; it can be used in adult scoliosis, in the elderly when pathological curves lead to a forward leaning posture or in adults after traumatic injuries. Bracing can be defined as the application of external corrective forces to the trunk; rigid supports or elastic bands can be used and braces can be custom-made or prefabricated. The state of research in the field of conservative treatment is insufficient and while it can be stated that there is some evidence to support bracing, we must also acknowledge that today we do not have a common and generally accepted knowledge base, and that instead, individual expertise still prevails, giving rise to different schools of thought on brace construction and principles of correction. The only way to improve the knowledge and understanding of brace type and brace function is to establish a single and comprehensive source of information about bracing. This is what the Scoliosis Journal is going to do through the "Brace Technology" Thematic Series, where technical papers coming from the different schools will be published

Nearly Monodispersion CoSm Alloy Nanoparticles Formed by an In-situ Rapid Cooling and Passivating Microfluidic Process

An in siturapid cooling and passivating microfluidic processhas been developed for the synthesis of nearly monodispersed cobalt samarium nanoparticles (NPs) with tunable crystal structures and surface properties. This process involves promoting the nucleation and growth of NPs at an elevated temperature and rapidly quenching the NP colloids in a solution containing a passivating reagent at a reduced temperature. We have shown that Cobalt samarium NPs having amorphous crystal structures and a thin passivating layer can be synthesized with uniform nonspherical shapes and size of about 4.8 nm. The amorphous CoSm NPs in our study have blocking temperature near 40 K and average coercivity of 225 Oe at 10 K. The NPs also exhibit high anisotropic magnetic properties with a wasp-waist hysteresis loop and a bias shift of coercivity due to the shape anisotropy and the exchange coupling between the core and the thin oxidized surface layer

Mixing patterns and the spread of close-contact infectious diseases

Surprisingly little is known regarding the human mixing patterns relevant to the spread of close-contact infections, such as measles, influenza and meningococcal disease. This study aims to estimate the number of partnerships that individuals make, their stability and the degree to which mixing is assortative with respect to age. We defined four levels of putative at-risk events from casual (physical contact without conversation) to intimate (contact of a sexual nature), and asked university student volunteers to record details on those they contacted at these levels on three separate days. We found that intimate contacts are stable over short time periods whereas there was no evidence of repeat casual contacts with the same individuals. The contacts were increasingly assortative as intimacy increased. Such information will aid the development and parameterisation of models of close contact diseases, and may have direct use in outbreak investigations

Systemic treatment with pulsed electromagnetic fields do not affect bone microarchitecture in osteoporotic rats

Purpose: Pulsed electromagnetic fields (PEMF) are currently used in the treatment of spinal fusions and non-unions. There are indications that PEMF might also be effective in the treatment of osteoporosis. In this study we examined whether whole-body PEMF treatment affects the bone microarchitecture in an osteoporotic rat model. Methods: Twenty-week-old female rats were ovariectomised (n020). Four different PEMF treatment protocols based on previous experimental studies and based on clinically used PEMF signals were examined (2 h/day, 5 days/week). A control group did not receive PEMF. At zero, three and six weeks cancellous and cortical bone architectural changes at the proximal tibia were evaluated using in vivo microCT scanning. Results: PEMF treatment did not induce any changes in cancellous or cortical bone compared to untreated controls. Conclusions: Although previous studies have shown strong effects of PEMF in osteoporosis we were unable to demonstrate this in any of the treatment protocols. Using in vivo microCT scanning we were able to identify small bone changes in time. Subtle differences in the experimental setup might explain the differences in study outcomes in the literature. Since PEMF treatment is safe, future experimental studies on the effect of PEMF on bone can better be performed directly on humans, eliminating the potential translation issues between animals and humans. In this study we found no support for the use of PEMF in the treatment of osteoporosis

Diffractive Dijet Production at sqrt(s)=630 and 1800 GeV at the Fermilab Tevatron

We report a measurement of the diffractive structure function $F_{jj}^D$ of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in $\bar pp$ collisions at $\sqrt s=630$ GeV at the Fermilab Tevatron. The ratio of $F_{jj}^D$ at $\sqrt s=630$ GeV to $F_{jj}^D$ obtained from a similar measurement at $\sqrt s=1800$ GeV is compared with expectations from QCD factorization and with theoretical predictions. We also report a measurement of the $\xi$ ($x$-Pomeron) and $\beta$ ($x$ of parton in Pomeron) dependence of $F_{jj}^D$ at $\sqrt s=1800$ GeV. In the region $0.035<\xi<0.095$, $|t|<1$ GeV$^2$ and $\beta<0.5$, $F_{jj}^D(\beta,\xi)$ is found to be of the form $\beta^{-1.0\pm 0.1} \xi^{-0.9\pm 0.1}$, which obeys $\beta$-$\xi$ factorization.Comment: LaTeX, 9 pages, Submitted to Phys. Rev. Letter

The Comprehensive Native Interactome of a Fully Functional Tagged Prion Protein

The enumeration of the interaction partners of the cellular prion protein, PrPC, may help clarifying its elusive molecular function. Here we added a carboxy proximal myc epitope tag to PrPC. When expressed in transgenic mice, PrPmyc carried a GPI anchor, was targeted to lipid rafts, and was glycosylated similarly to PrPC. PrPmyc antagonized the toxicity of truncated PrP, restored prion infectibility of PrPC-deficient mice, and was physically incorporated into PrPSc aggregates, indicating that it possessed all functional characteristics of genuine PrPC. We then immunopurified myc epitope-containing protein complexes from PrPmyc transgenic mouse brains. Gentle differential elution with epitope-mimetic decapeptides, or a scrambled version thereof, yielded 96 specifically released proteins. Quantitative mass spectrometry with isotope-coded tags identified seven proteins which co-eluted equimolarly with PrPC and may represent component of a multiprotein complex. Selected PrPC interactors were validated using independent methods. Several of these proteins appear to exert functions in axomyelinic maintenance

A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns