Putting hydrodynamic interactions to work: tagged particle separation

Separation of magnetically tagged cells is performed by attaching markers to a subset of cells in suspension and applying fields to pull from them in a variety of ways. The magnetic force is proportional to the field gradient, and the hydrodynamic interactions play only a passive, adverse role. Here we propose using a homogeneous rotating magnetic field only to make tagged particles rotate, and then performing the actual separation by means of hydrodynamic interactions, which thus play an active role. The method, which we explore here theoretically and by means of numerical simulations, lends itself naturally to sorting on large scales.Comment: Version accepted for publication - Europhysics Letter

Cholesterol-Metabolizing Enzyme Cytochrome P450 46A1 as a Pharmacologic Target for Alzheimer’s Disease

Cytochrome P450 46A1 (CYP46A1 or cholesterol 24-hydroxylase) controls cholesterol elimination from the brain and plays a role in higher order brain functions. Genetically enhanced CYP46A1 expression in mouse models of Alzheimer's disease mitigates the manifestations of this disease. We enhanced CYP46A1 activity pharmacologically by treating 5XFAD mice, a model of rapid amyloidogenesis, with a low dose of the anti-HIV medication efavirenz. Efavirenz was administered from 1 to 9 months of age, and mice were evaluated at specific time points. At one month of age, cholesterol homeostasis was already disturbed in the brain of 5XFAD mice. Nevertheless, efavirenz activated CYP46A1 and mouse cerebral cholesterol turnover during the first four months of administration. This treatment time also reduced amyloid burden and microglia activation in the cortex and subiculum of 5XFAD mice as well as protein levels of amyloid precursor protein and the expression of several genes involved in inflammatory response. However, mouse short-term memory and long-term spatial memory were impaired, whereas learning in the context-dependent fear test was improved. Additional four months of drug administration (a total of eight months of treatment) improved long-term spatial memory in the treated as compared to the untreated mice, further decreased amyloid-β content in 5XFAD brain, and also decreased the mortality rate among male mice. We propose a mechanistic model unifying the observed efavirenz effects. We suggest that CYP46A1 activation by efavirenz could be a new anti-Alzheimer's disease treatment and a tool to study and identify normal and pathological brain processes affected by cholesterol maintenance

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of an NBC when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed

Urgent need to clarify the definition of chronic critical limb ischemia - a position paper from the European Society for Vascular Medicine

Chronic critical lower limb ischemia (CLI) has been defined as ischemia that endangers the leg. An attempt was made to give a precise definition of CLI, based on clinical and hemodynamic data (Second European Consensus). CLI may be easily defined from a clinical point of view as rest pain of the distal foot or gangrene or ulceration. It is probably useful to add leg ulcers of other origin which do not heal because of severe ischemia, and to consider the impact of frailty on adverse outcome. From a hemodynamic viewpoint there is no consensus and most of the existing classifications are not based upon evidence. We should thus propose a definition and then validate it in a prospective cohort in order to define the patients at major risk of amputation, and also to define the categories of patients whose prognosis is improved by revascularisation. From today\u27s available data, it seems clear that the patients with a systolic toe pressure (STP) below 30 mmHg must be revascularised whenever possible. However other patients with clinically suspected CLI and STP above 30 mmHg must be evaluated and treated in specialised vascular units and revascularisation has to be discussed on a case by case basis, taking into account other data such as the WiFi classification for ulcers.In conclusion, many useful but at times contradictory definitions of CLI have been suggested. Only a few have taken into account evidence, and none have been validated prospectively. This paper aims to address this and to give notice that a CLI registry within Europe will be set up to prospectively validate, or not, the previous and suggested definitions of CLI

Centrality Behaviour of J/ψ\psi Production in Na50

The J/$\psi$ production in 158 A GeV Pb-Pb interactions is studied, in the dimuon decay channel, as a function of centrality, as measured with the electromagnetic or with the very forward calorimeters. After a first sharp variation at mid centrality, both patterns continue to fall down and exhibit a curvature change at high centrality values. This trend excludes any conventional hadronic model and is in agreement with a deconfined quark-gluon phase scenario. We report also preliminary results on the measured charged multiplicity, as given by a dedicated detector.Comment: 5 pages, 7 figures (in eps) talk given at XXXI International Symposium on Multiparticle Dynamics, Sep. 1-7, 2001, Datong China URL http://ismd31.ccnu.edu.cn

A cluster-randomised, controlled trial to assess the impact of a workplace osteoporosis prevention intervention on the dietary and physical activity behaviours of working women: study protocol

Background Osteoporosis is a debilitating disease and its risk can be reduced through adequate calcium consumption and physical activity. This protocol paper describes a workplace-based intervention targeting behaviour change in premenopausal women working in sedentary occupations. Method/Design A cluster-randomised design was used, comparing the efficacy of a tailored intervention to standard care. Workplaces were the clusters and units of randomisation and intervention. Sample size calculations incorporated the cluster design. Final number of clusters was determined to be 16, based on a cluster size of 20 and calcium intake parameters (effect size 250 mg, ICC 0.5 and standard deviation 290 mg) as it required the highest number of clusters. Sixteen workplaces were recruited from a pool of 97 workplaces and randomly assigned to intervention and control arms (eight in each). Women meeting specified inclusion criteria were then recruited to participate. Workplaces in the intervention arm received three participatory workshops and organisation wide educational activities. Workplaces in the control/standard care arm received print resources. Intervention workshops were guided by self-efficacy theory and included participatory activities such as goal setting, problem solving, local food sampling, exercise trials, group discussion and behaviour feedback. Outcomes measures were calcium intake (milligrams/day) and physical activity level (duration: minutes/week), measured at baseline, four weeks and six months post intervention. Discussion This study addresses the current lack of evidence for behaviour change interventions focussing on osteoporosis prevention. It addresses missed opportunities of using workplaces as a platform to target high-risk individuals with sedentary occupations. The intervention was designed to modify behaviour levels to bring about risk reduction. It is the first to address dietary and physical activity components each with unique intervention strategies in the context of osteoporosis prevention. The intervention used locally relevant behavioural strategies previously shown to support good outcomes in other countries. The combination of these elements have not been incorporated in similar studies in the past, supporting the study hypothesis that the intervention will be more efficacious than standard practice in osteoporosis prevention through improvements in calcium intake and physical activity

Low mass dimuon production in proton and ion induced interactions at SPS

The low mass dimuon spectra collected in p-U collisions by the NA38 experiment significantly exceeds the total cross section expected from previous analysis, done by other experiments. The `excess' events have a harder \pt\ distribution than the muon pairs from $\eta$ and $\omega$ Dalitz decays, expected to dominate the mass window 0.4--0.65~GeV/$c^2$. We conjecture that the excess events might be due to \qqbar\ annihilations, negligible at low \pt\ but made visible by the \mt\ cut applied in the NA38 data. Taking this assumption to parametrise the p-U spectra, we proceed with the analysis of the S-Cu, S-U and Pb-Pb data, collected by the NA38 and NA50 experiments, where we find that the measured mass spectra does not seem to exceed the expected low mass `cocktail' by more than 20\,\%

Pseudorapidity distributions of charged particles as a function of centrality in Pb-Pb collisions at 158 and 40 GeV per nucleon incident energy

NA5

Scaling of charged particle multiplicity in Pb-Pb collisions at SPS energies

The charged particle multiplicity distribution $dN_{ch}/d\eta$ has been measured by the NA50 experiment in Pb--Pb collisions at the CERN SPS. Measurements were done at incident energies of 40 and 158 GeV per nucleon over a broad impact parameter range. The multiplicity distributions are studied as a function of centrality using the number of participating nucleons ($N_{part}$), or the number of binary nucleon--nucleon collisions ($N_{coll}$). Their values at midrapidity exhibit a power law scaling behaviour given by $N_{part}^{1.00}$ and $N_{coll}^{0.75}$ at 158 GeV. Compatible results are found for the scaling behaviour at 40 GeV. The width of the $dN_{ch}/d\eta$ distributions is larger at 158 than at 40 GeV/nucleon and decreases slightly with centrality at both energies. Our results are compared to similar studies performed by other experiments both at the CERN SPS and at RHIC.