RFID Transponders : Link between information and material flows. How reliable are identification procedures?

Along with the growing complexity of logistic chains the demand for transparency of informations has increased. The use of intelligent RFID-Technology offers the possibility to optimize and control all capacities in use, since it enables the identification and tracking of goods alongside the entire supply chain. Every single product can be located at any given time and a multitude of current and historical data can be transferred. The interaction of the flow of material and the flow of information between the various process steps can be optimized by using RFID-Technology since it guarantees that all required data is available at the right time and at the right place. The local accessibility and convertibility of data allows a flexible, decentralised control of logistic systems. As additional advantages of RFID-Components can be considered that they are individually writable and that their identification can be achieved over considerable distances even if there is no intervisibility between tag and reader. The use of RFID-Transponder opens up new potentials regarding process security, reduction of logistic costs or availability of products. These advantages depend on reliability of the identification processes. The undisputed potentials that are made accessible by the use of RFID-Elements can only be beneficial when the informations that are decentralised and attached to goods and loading equipment can be reliably retrieved at the required points. The communication between tag and reader can be influenced by different materials such as metal, that can disturbed or complicate the radio contact. The communications reliability is subject of various tests and experiments that analyse the effects of different filling materials as well as different alignments of tags on the loading equipment.

Pasture Conditions at the Initiation of Grazing to Optimize Forage Productivity: A Progress Report

To determine environmental, soil, and sward effects at the initiation of cattle grazing in the spring on seasonal (forage accumulated during the grazing season) and cumulative (seasonal + initial forage mass) forage accumulation (FA), 15 commercial cow-calf producers from southern Iowa were selected by historical initial grazing date. At grazing initiation, twelve .25-m2 samples were hand-clipped from each pasture and sward heights (SH) measured with a falling plane meter (4.8 kg/m2) to determine initial forage mass. At each location, soil temperature and load bearing capacity (LBC) were measured and a soil sample was collected to measure pH and moisture, P, and K concentrations. Cumulative degree-days (base=3.85°C) and precipitation at grazing initiation were calculated from NOAA records. At the beginning of each month, at least three grazing exclosures were placed on each grazed pasture to determine monthly FA. SH in each exclosure was recorded, and a .25-m2 forage sample was hand-clipped proximate to each exclosure. At the end of each month, SH was recorded and .25-m2 hand-clipped forage samples from inside exclosures were obtained. In linear regressions, cumulative and seasonal SH increased with greater soil P (r2=.5049 and .5417), soil K (r2=.4675 and .4397), and initial forage mass (r2=.1984 and .2801). Seasonal SH increased with earlier initial grazing dates (r2=.1996) and less accumulated degree-days (r2=.2364). Cumulative and seasonal FA increased with earlier initial grazing dates (r2=.2106 and .3744), lower soil temperatures (r2=.2617 and.2874), and greater soil P (r2=.3489 and .2598). Cumulative FA increased with greater soil K (r2=.4675). In quadratic regressions, cumulative and seasonal SH were correlated to soil P (r2=.6310 and .5310) and soil K (r2=.5095 and.4401). Cumulative and seasonal FA were correlated to degree days (r2=.3630 and.4013) and initial grazing date (r2=.3425 and .4088). Cumulative FA was correlated to soil P (r2=.3539), and seasonal FA was correlated to soil moisture (r2=.3688).

Thermoreversible hyaluronan-based hydrogel supports in vitro and ex vivo disc-like differentiation of human mesenchymal stem cells

BACKGROUND CONTEXT The fate of human mesenchymal stem cells (hMSCs) supplied to the degenerating intervertebral disc (IVD) is still not fully understood and can be negatively affected by low oxygen, pH, and glucose concentration of the IVD environment. The hMSC survival and yield upon injection of compromised IVD could be improved by the use of an appropriate carrier and/or by predifferentiation of hMSCs before injection. PURPOSE To optimize hMSC culture conditions in thermoreversible hyaluronan-based hydrogel, hyaluronan-poly(N-isopropylacrylamide) (HA-pNIPAM), to achieve differentiation toward the disc phenotype in vitro, and evaluate whether preconditioning contributes to a better hMSC response ex vivo. STUDY DESIGN In vitro and ex vivo whole-organ culture of hMSCs. METHODS In vitro cultures of hMSCs were conducted in HA-pNIPAM and alginate for 1 week under hypoxia in chondropermissive medium alone and with the supplementation of transforming growth factor β1 or growth and differentiation factor 5 (GDF-5). Ex vivo, hMSCs were either suspended in HA-pNIPAM and directly supplied to the IVDs or predifferentiated with GDF-5 for 1 week in HA-pNIPAM and then supplied to the IVDs. Cell viability was evaluated by Live-Dead assay, and DNA, glycosaminoglycan (GAG), and gene expression profiles were used to assess hMSC differentiation toward the disc phenotype. RESULTS The HA-pNIPAM induced hMSC differentiation toward the disc phenotype more effectively than alginate: in vitro, higher GAG/DNA ratio and higher collagen type II, SOX9, cytokeratin-19, cluster of differentiation 24, and forkhead box protein F1 expressions were found for hMSCs cultured in HA-pNIPAM compared with those cultured in alginate, regardless of the addition of growth factors. Ex vivo, direct combination of HA-pNIPAM with the disc environment induced a stronger disc-like differentiation of hMSCs than predifferentiation of hMSCs followed by their delivery to the discs. CONCLUSIONS Hyaluronan-based thermoreversible hydrogel supports hMSC differentiation toward the disc phenotype without the need for growth factor supplementation in vitro and ex vivo. Further in vivo studies are required to confirm the suitability of this hydrogel as an effective stem cell carrier for the treatment of IVD degeneration.

Characteristics and functional relevance of apolipoprotein-A1 and cholesterol binding in mammary gland tissues and epithelial cells

Cholesterol in milk is derived from the circulating blood through a complex transport process involving the mammary alveolar epithelium. Details of the mechanisms involved in this transfer are unclear. Apolipoprotein-AI (apoA-I) is an acceptor of cellular cholesterol effluxed by the ATP-binding cassette (ABC) transporter A1 (ABCA1). We aimed to 1) determine the binding characteristics of (125)I-apoA-I and (3)H-cholesterol to enriched plasma membrane vesicles (EPM) isolated from lactating and non-lactating bovine mammary glands (MG), 2) optimize the components of an in vitro model describing cellular (3)H-cholesterol efflux in primary bovine mammary epithelial cells (MeBo), and 3) assess the vectorial cholesterol transport in MeBo using Transwell(®) plates. The amounts of isolated EPM and the maximal binding capacity of (125)I-apoA-I to EPM differed depending on the MG's physiological state, while the kinetics of (3)H-cholesterol and (125)I-apoA-I binding were similar. (3)H-cholesterol incorporated maximally to EPM after 25±9 min. The time to achieve the half-maximum binding of (125)I-apoA-I at equilibrium was 3.3±0.6 min. The dissociation constant (KD) of (125)I-apoA-I ranged between 40-74 nmol/L. Cholesterol loading to EPM increased both cholesterol content and (125)I-apoA-I binding. The ABCA1 inhibitor Probucol displaced (125)I-apoA-I binding to EPM and reduced (3)H-cholesterol efflux in MeBo. Time-dependent (3)H-cholesterol uptake and efflux showed inverse patterns. The defined binding characteristics of cholesterol and apoA-I served to establish an efficient and significantly shorter cholesterol efflux protocol that had been used in MeBo. The application of this protocol in Transwell(®) plates with the upper chamber mimicking the apical (milk-facing) and the bottom chamber corresponding to the basolateral (blood-facing) side of cells showed that the degree of (3)H-cholesterol efflux in MeBo differed significantly between the apical and basolateral aspects. Our findings support the importance of the apoA-I/ABCA1 pathway in MG cholesterol transport and suggest its role in influencing milk composition and directing cholesterol back into the bloodstream.

A validated assay by liquid chromatography-tandem mass spectrometry for the simultaneous quantification of elvitegravir and rilpivirine in HIV positive patients

Because of the large variability in the pharmacokinetics of anti-HIV drugs, therapeutic drug monitoring in patients may contribute to optimize the overall efficacy and safety of antiretroviral therapy. An LC–MS/MS method for the simultaneous assay in plasma of the novel antiretroviral agents rilpivirine (RPV) and elvitegravir (EVG) has been developed to that endeavor. Plasma samples (100 μL) extraction is performed by protein precipitation with acetonitrile, and the supernatant is subsequently diluted 1:1 with 20-mM ammonium acetate/MeOH 50:50. After reverse-phase chromatography, quantification of RPV and EVG, using matrix-matched calibration samples, is performed by electrospray ionization–triple quadrupole mass spectrometry by selected reaction monitoring detection using the positive mode. The stable isotopic-labeled compounds RPV-13C6 and EVG-D6 were used as internal standards. The method was validated according to FDA recommendations, including assessment of extraction yield, matrix effects variability (<6.4%), as well as EVG and RPV short and long-term stability in plasma. Calibration curves were validated over the clinically relevant concentrations ranging from 5 to 2500 ng/ml for RPV and from 50 to 5000 ng/ml for EVG. The method is precise (inter-day CV%: 3–6.3%) and accurate (3.8–7.2%). Plasma samples were found to be stable (<15%) in all considered conditions (RT/48 h, +4°C/48 h, −20°C/3 months and 60°C/1 h). Selected metabolite profiles analysis in patients' samples revealed the presence of EVG glucuronide, that was well separated from parent EVG, allowing to exclude potential interferences through the in-source dissociation of glucuronide to parent drug. This new, rapid and robust LCMS/MS assay for the simultaneous quantification of plasma concentrations of these two major new anti-HIV drugs EVG and RPV offers an efficient analytical tool for clinical pharmacokinetics studies and routine therapeutic drug monitoring service.

Finite element based estimation of contact areas and pressures of the human scaphoid in various functional positions of the hand

The scaphoid is the most frequently fractured carpal bone. When investigating fixation stability, which may influence healing, knowledge of forces and moments acting on the scaphoid is essential. The aim of this study was to evaluate cartilage contact forces acting on the intact scaphoid in various functional wrist positions using finite element modeling. A novel methodology was utilized as an attempt to overcome some limitations of earlier studies, namely, relatively coarse imaging resolution to assess geometry, assumption of idealized cartilage thicknesses and neglected cartilage pre-stresses in the unloaded joint. Carpal bone positions and articular cartilage geometry were obtained independently by means of high resolution CT imaging and incorporated into finite element (FE) models of the human wrist in eight functional positions. Displacement driven FE analyses were used to resolve inter-penetration of cartilage layers, and provided contact areas, forces and pressure distribution for the scaphoid bone. The results were in the range reported by previous studies. Novel findings of this study were: (i) cartilage thickness was found to be heterogeneous for each bone and vary considerably between carpal bones; (ii) this heterogeneity largely influenced the FE results and (iii) the forces acting on the scaphoid in the unloaded wrist were found to be significant. As major limitations, accuracy of the method was found to be relatively low, and the results could not be compared to independent experiments. The obtained results will be used in a following study to evaluate existing and recently developed screws used to fix scaphoid fractures.

Modern charge density studies: the entanglement of experiment and theory

This tutorial review article is intended to provide a general guidance to a reader interested to learn about the methodologies to obtain accurate electron density mapping in molecules and crystalline solids, from theory or from experiment, and to carry out a sensible interpretation of the results, for chemical, biochemical or materials science applications. The review mainly focuses on X-ray diffraction techniques and refinement of experimental models, in particular multipolar models. Neutron diffraction, which was widely used in the past to fix accurate positions of atoms, is now used for more specific purposes. The review illustrates three principal analyses of the experimental or theoretical electron density, based on quantum chemical, semi-empirical or empirical interpretation schemes, such as the quantum theory of atoms in molecules, the semi-classical evaluation of interaction energies and the Hirshfeld analysis. In particular, it is shown that a simple topological analysis based on a partition of the electron density cannot alone reveal the whole nature of chemical bonding. More information based on the pair density is necessary. A connection between quantum mechanics and observable quantities is given in order to provide the physical grounds to explain the observations and to justify the interpretations.

Transport and uptake of immunogenic lipids

An increasing number of lipid mediators have been identified as key modulators of immunity. Among these is a family of glycolipids capable of cellular uptake, loading onto the MHC-like molecule CD1d and stimulation of NKT cells. NKT cells are particularly interesting because they bridge innate and adaptive immunity by coordinating the early events of dendritic cell maturation, recruitment of NK cells, CD4 and CD8 T cells, and B cells at the site of microbial injury. As such, their therapeutic manipulation could be of the greatest interest in vaccine design or active immunotherapy. However, the use of NKT cells as cellular adjuvant of immunity in the clinic will require a better knowledge of the pharmacology of lipid agonists in order to optimize their action and avoid potential unseen off-target effects. We have been studying extracellular transport and cellular uptake of NKT agonists for the past few years. This field is confronted to a very limited prior knowledge and a small set of usable tools. New technology must be put in place and adapted to answering basic immunology questions related to NKT cells. The intimate link between the pharmacology of glycolipids and lipid metabolism makes us believe that great variations of bioactivity could be seen in the general population when NKT agonists are used therapeutically.

Energy harvesting through arterial wall deformation: A FEM approach to fluid–structure interactions and magneto-hydrodynamics

Engineers are confronted with the energy demand of active medical implants in patients with increasing life expectancy. Scavenging energy from the patient’s body is envisioned as an alternative to conventional power sources. Joining in this effort towards human-powered implants, we propose an innovative concept that combines the deformation of an artery resulting from the arterial pressure pulse with a transduction mechanism based on magneto-hydrodynamics. To overcome certain limitations of a preliminary analytical study on this topic, we demonstrate here a more accurate model of our generator by implementing a three-dimensional multiphysics finite element method (FEM) simulation combining solid mechanics, fluid mechanics, electric and magnetic fields as well as the corresponding couplings. This simulation is used to optimize the generator with respect to several design parameters. A first validation is obtained by comparing the results of the FEM simulation with those of the analytical approach adopted in our previous study. With an expected overall conversion efficiency of 20% and an average output power of 30 μW, our generator outperforms previous devices based on arterial wall deformation by more than two orders of magnitude. Most importantly, our generator provides sufficient power to supply a cardiac pacemaker.

Isolation and {\it in vitro}-immunosuppressive characterization of a novel cyclosporine metabolite

Cyclosporine (CsA) has shown great benefit to organ transplant recipients, as an immunosuppressive drug. To optimize CsA immunosuppressive therapy, pharmacodynamic evaluation of serial patient serum samples after CsA administration, using mixed lymphocyte culture (MLC) assays, revealed in vitro serum immunosuppressive activity of a CsA-like, ether-extractable component, associated with good clinical outcome in vivo. Since the in vitro immunosuppressive CsA metabolites, M-17 and M-1, are erythrocyte-bound, the immunosuppressive activity demonstrated in patient serum suggests that other immunosuppressive metabolites need exist. To test this hypothesis and obtain CsA metabolites for study, ether-extracted bile from tritiated and nonradioactive CsA-treated pigs was processed by novel high performance liquid and thin-layer chromatography (HPLC and HPTLC) techniques. Initial MLC screening of potential metabolites revealed a component, designated M-E, to have immunosuppressive activity. Pig bile-derived M-E was characterized as a CsA metabolite, by radioactive CsA tracer studies, by 56% crossreactivity in CsA radioimmunoassay, and by mass spectrometric (MS) analysis. MS revealed a CsA ring structure, hydroxylated at a site other than at amino acid one. M-E was different than M-1 and M-17, as demonstrated by different retention properties for each metabolite, using HPTLC and a novel rhodamine B/ $\alpha$-cyclodextrin stain, and using HPLC, performed by Sandoz, that revealed M-E to be different than previously characterized metabolites. The immunosuppressive activity of M-E was quantified by determination of mean metabolite potency ratio in human MLC assays, which was found to be 0.79 $\pm$ 0.23 (CsA, 1.0). Similar to parent drug, M-E revealed inter-individual differences in its immunosuppressive activity. M-E demonstrates inhibition of IL-2 production by concanavalin A stimulated C3H mouse spleen cells, similar to CsA, as determined with an IL-2 dependent mouse cytotoxic T-cell line. ^

Patient classification system: An integrated method for measuring nursing intensity and optimizing resource allocation

A patient classification system was developed integrating a patient acuity instrument with a computerized nursing distribution method based on a linear programming model. The system was designed for real-time measurement of patient acuity (workload) and allocation of nursing personnel to optimize the utilization of resources.^ The acuity instrument was a prototype tool with eight categories of patients defined by patient severity and nursing intensity parameters. From this tool, the demand for nursing care was defined in patient points with one point equal to one hour of RN time. Validity and reliability of the instrument was determined as follows: (1) Content validity by a panel of expert nurses; (2) predictive validity through a paired t-test analysis of preshift and postshift categorization of patients; (3) initial reliability by a one month pilot of the instrument in a practice setting; and (4) interrater reliability by the Kappa statistic.^ The nursing distribution system was a linear programming model using a branch and bound technique for obtaining integer solutions. The objective function was to minimize the total number of nursing personnel used by optimally assigning the staff to meet the acuity needs of the units. A penalty weight was used as a coefficient of the objective function variables to define priorities for allocation of staff.^ The demand constraints were requirements to meet the total acuity points needed for each unit and to have a minimum number of RNs on each unit. Supply constraints were: (1) total availability of each type of staff and the value of that staff member (value was determined relative to that type of staff's ability to perform the job function of an RN (i.e., value for eight hours RN = 8 points, LVN = 6 points); (2) number of personnel available for floating between units.^ The capability of the model to assign staff quantitatively and qualitatively equal to the manual method was established by a thirty day comparison. Sensitivity testing demonstrated appropriate adjustment of the optimal solution to changes in penalty coefficients in the objective function and to acuity totals in the demand constraints.^ Further investigation of the model documented: correct adjustment of assignments in response to staff value changes; and cost minimization by an addition of a dollar coefficient to the objective function. ^

Optimizing Models of the North Atlantic Spring Bloom Using Physical, Chemical and Bio-Optical Observations from a Lagrangian Float

The North Atlantic spring bloom is one of the main events that lead to carbon export to the deep ocean and drive oceanic uptake of CO(2) from the atmosphere. Here we use a suite of physical, bio-optical and chemical measurements made during the 2008 spring bloom to optimize and compare three different models of biological carbon export. The observations are from a Lagrangian float that operated south of Iceland from early April to late June, and were calibrated with ship-based measurements. The simplest model is representative of typical NPZD models used for the North Atlantic, while the most complex model explicitly includes diatoms and the formation of fast sinking diatom aggregates and cysts under silicate limitation. We carried out a variational optimization and error analysis for the biological parameters of all three models, and compared their ability to replicate the observations. The observations were sufficient to constrain most phytoplankton-related model parameters to accuracies of better than 15 %. However, the lack of zooplankton observations leads to large uncertainties in model parameters for grazing. The simulated vertical carbon flux at 100 m depth is similar between models and agrees well with available observations, but at 600 m the simulated flux is larger by a factor of 2.5 to 4.5 for the model with diatom aggregation. While none of the models can be formally rejected based on their misfit with the available observations, the model that includes export by diatom aggregation has a statistically significant better fit to the observations and more accurately represents the mechanisms and timing of carbon export based on observations not included in the optimization. Thus models that accurately simulate the upper 100 m do not necessarily accurately simulate export to deeper depths.

Virtual Infrastructures as a Service enabling Converged Optical Networks and Data Centres

Abstract Cloud computing service emerged as an essential component of the Enterprise {IT} infrastructure. Migration towards a full range and large-scale convergence of Cloud and network services has become the current trend for addressing requirements of the Cloud environment. Our approach takes the infrastructure as a service paradigm to build converged virtual infrastructures, which allow offering tailored performance and enable multi-tenancy over a common physical infrastructure. Thanks to virtualization, new exploitation activities of the physical infrastructures may arise for both transport network and Data Centres services. This approach makes network and Data Centres’ resources dedicated to Cloud Computing to converge on the same flexible and scalable level. The work presented here is based on the automation of the virtual infrastructure provisioning service. On top of the virtual infrastructures, a coordinated operation and control of the different resources is performed with the objective of automatically tailoring connectivity services to the Cloud service dynamics. Furthermore, in order to support elasticity of the Cloud services through the optical network, dynamic re-planning features have been provided to the virtual infrastructure service, which allows scaling up or down existing virtual infrastructures to optimize resource utilisation and dynamically adapt to users’ demands. Thus, the dynamic re-planning of the service becomes key component for the coordination of Cloud and optical network resource in an optimal way in terms of resource utilisation. The presented work is complemented with a use case of the virtual infrastructure service being adopted in a distributed Enterprise Information System, that scales up and down as a function of the application requests.

[Gender differences in acute and chronic pain conditions. Implications for diagnosis and therapy].

Gender differences can influence incidence and outcome of acute and chronic pain conditions. The reasons are to be found in genetic factors, hormonal effects and differences in anatomy and physiology. Furthermore differences relating to psychiatric comorbidities (i.e. depression) and psychosocial factors (roles, coping strategies) have been demonstrated. Men and women differ in the response to drugs and other treatments. They are differently affected by side effects of drugs. There is a gender bias in diagnosis and therapy. There is a need to study the influence of gender, age and race in order to optimize treatment towards a more individualized therapy. This article highlights already identified differences.