Helminths in the hygiene hypothesis:Sooner or later?

There is increasing recognition that exposures to infectious agents evoke fundamental effects on the development and behaviour of the immune system. Moreover, where infections (especially parasitic infections) have declined, immune responses appear to be increasingly prone to hyperactivity. For example, epidemiological studies of parasite-endemic areas indicate that prenatal or early-life experience of infections can imprint an individual's immunological reactivity. However, the ability of helminths to dampen pathology in established inflammatory diseases implies that they can have therapeutic effects even if the immune system has developed in a low-infection setting. With recent investigations of how parasites are able to modulate host immune pathology at the level of individual parasite molecules and host cell populations, we are now able to dissect the nature of the host–parasite interaction at both the initiation and recall phases of the immune response. Thus the question remains – is the influence of parasites on immunity one that acts primarily in early life, and at initiation of the immune response, or in adulthood and when recall responses occur? In short, parasite immunosuppression – sooner or later

Data management study, volume 5. Appendix E - Contractor data package quality assurance /QA/ Final report

Manufacturing verification tests for quality assurance and control data management on Voyager spacecraf

Transcritical shallow-water flow past topography: finite-amplitude theory

We consider shallow-water flow past a broad bottom ridge, localized in the flow direction, using the framework of the forced SuGardner (SG) system of equations, with a primary focus on the transcritical regime when the Froude number of the oncoming flow is close to unity. These equations are an asymptotic long-wave approximation of the full Euler system, obtained without a simultaneous expansion in the wave amplitude, and hence are expected to be superior to the usual weakly nonlinear Boussinesq-type models in reproducing the quantitative features of fully nonlinear shallow-water flows. A combination of the local transcritical hydraulic solution over the localized topography, which produces upstream and downstream hydraulic jumps, and unsteady undular bore solutions describing the resolution of these hydraulic jumps, is used to describe various flow regimes depending on the combination of the topography height and the Froude number. We take advantage of the recently developed modulation theory of SG undular bores to derive the main parameters of transcritical fully nonlinear shallow-water flow, such as the leading solitary wave amplitudes for the upstream and downstream undular bores, the speeds of the undular bores edges and the drag force. Our results confirm that most of the features of the previously developed description in the framework of the unidirectional forced Kortewegde Vries (KdV) model hold up qualitatively for finite amplitude waves, while the quantitative description can be obtained in the framework of the bidirectional forced SG system. Our analytic solutions agree with numerical simulations of the forced SG equations within the range of applicability of these equations

The crystal structure of calcite III

The crystal structure of calcite III has been deduced from existing high pressure powder X-ray diffraction patterns, based on the assumption that it is a displacive modification of the calcite I structure. The structure is monoclinic with space group C2 and a Z of 6. There are two Ca and two C positions, and five O positions, and atom coordinates have been refined by distance-least-squares methods to give reasonable octahedral coordination for Ca and parallel, planar CO_3 groups. Unit cell parameters refined from a published powder diffraction pattern at 4.1 GPa are: a = 8.746(8)Å; b = 4.685(5)Å; c = 8.275(8)Å; and β= 94.4°. The structure has a calculated density of 2.949 Mg/m³ at 4.1 GPa which is less than that of aragonite at this pressure and consistent with early piston cylinder studies. This implies that calcite III is indeed a metastable intermediary between calcite I and aragonite

Creatinine biosensors: principles and designs

Creatinine biosensors, based on both potentiometric and amperometric devices, have been created. However, there are significant problems still to be addressed, including the balance between sensitivity and selectivity, interference rejection and sensor stability. In addition, many devices still rely on a dual-sensor approach for creatine and creatinine subtractive measurements. However, creatinine biosensors appear close to attaining the performance goals necessary for their widespread application. This article looks at the operating principle and design of both potentiometric and amperometric creatinine biosensors, and shows how the design of these devices affects their performance

Immediate replacement of fishing with dairying by the earliest farmers of the NE Atlantic archipelagos

The appearance of farming, from its inception in the Near East around 12 000 years ago, finally reached the northwestern extremes of Europe by the fourth millennium BC or shortly thereafter. Various models have been invoked to explain the Neolithization of northern Europe; however, resolving these different scenarios has proved problematic due to poor faunal preservation and the lack of specificity achievable for commonly applied proxies. Here, we present new multi-proxy evidence, which qualitatively and quantitatively maps subsistence change in the northeast Atlantic archipelagos from the Late Mesolithic into the Neolithic and beyond. A model involving significant retention of hunter–gatherer–fisher influences was tested against one of the dominant adoptions of farming using a novel suite of lipid biomarkers, including dihydroxy fatty acids, ω-(o-alkylphenyl)alkanoic acids and stable carbon isotope signatures of individual fatty acids preserved in cooking vessels. These new findings, together with archaeozoological and human skeletal collagen bulk stable carbon isotope proxies, unequivocally confirm rejection of marine resources by early farmers coinciding with the adoption of intensive dairy farming. This pattern of Neolithization contrasts markedly to that occurring contemporaneously in the Baltic, suggesting that geographically distinct ecological and cultural influences dictated the evolution of subsistence practices at this critical phase of European prehistory

Elucidation of the mode of action of a conductive polymer-based electrochemical immunosensor.

An amperometric biosensor has been developed, incorporating the electroactive polymer, polyaniline (PANI), which undergoes redox cycling, and can couple electrons directly from the enzyme active site, to the electrode surface. Construction of this sensor was achieved by electropolymerisation of polyvinylsulphonate-doped aniline onto the surface of a screen-printed carbon-paste electrode. Biomolecules could then be doped onto the surface of the polymer by electrostatic interactions with the polymer backbone. A key component in a biosensor is the recognition molecule and its immobilisation. This study investigates this process of protein immobilisation using amperometric and colorimetric techniques. Immobilisation of protein (enzyme or antibody) onto the transducer is achieved by electrostatic interactions. By applying bovine serum albumin (BSA) electrostatically at the electrode, efficient blocking of the electrode surface from the bulk solution was achieved above approximately 0.75 mg/ml. When horseradish peroxidase was immobilised on the electrode surface at various concentrations, optimal amperometric responses were achieved at approximately the same protein concentration. Determination of the number of molecules of protein immobilised on the surface of the electrode at this concentration was done using a colorimetric enzyme assay. It was found that under optimal immobilisation conditions, a protein monolayer was formed at the electrode surface. In the case of enzymes such as horseradish peroxidase (HRP), this provides simultaneous blocking of the electrode surface from bulk solution interactions as well as yielding optimal electron transfer properties

Immunoelectrochemical methods immunoelectrochemical of hormone anaylsis

Over the last decade, there has been considerable interest in the development of immunoelectrochemical assays, mainly due to the advantages offered by the combination of the selectivity of immunoassays with the great sensitivity and simplicity of modern electroanalytical techniques. However, immunoelectrochemical assays have not yet been exploited commercially, as transitions from the laboratory bench to large-scale manufacturing has proved difficult. The system described is an amperometric peroxide biosensor prepared by electrochemical deposition of horseradish peroxidase on an electroactive polymer, polyaniline. Polyaniline brings about mediatorless redox coupling between the electrode and biomolecular components attached to the surface. This assay will be the stepping-stone to developing an immunoelectrochemical method for the analysis of human chorionic gonadotropin (hCG), and other female hormones. The assay initially utilises glassy carbon electrodes for preliminary data, before being replaced with a commercially available electrode Euroflash TM, produced by Inverness Medical Limited TM. This electrode was utilised with a view to producing an electrochemical assay that complies with manufacturing requirements

Reagentless glucose biosensor based on the direct electrochemistry of glucose oxidase on carbon nanotube-modified electrodes

The direct electrochemistry of glucose oxidase (GOD) was revealed at a carbon nanotube (CNT)-modified glassy carbon electrode, where the enzyme was immobilized with a chitosan film containing gold nanoparticles. The immobilized GOD displays a pair of redox peaks in pH 7.4 phosphate buffer solutions (PBS) with the formal potential of about -455 mV (vs. Ag/AgCl) and shows a surface-controlled electrode process. Bioactivity remains good, along with effective catalysis of the reduction of oxygen. In the presence of dissolved oxygen, the reduction peak current decreased gradually with the addition of glucose, which could be used for reagentless detection of glucose with a linear range from 0.04 to 1.0 mM. The proposed glucose biosensor exhibited high sensitivity, good stability and reproducibility, and was also insensitive to common interferences such as ascorbic and uric acid. The excellent performance of the reagentless biosensor is attributed to the effective enhancement of electron transfer between enzyme and electrode surface by CNTs, and the biocompatible environment that the chitosan film containing gold nanoparticles provides for immobilized GOD