Assessment of regional myocardial uptake and metabolism of omega-(p-123I-phenyl) pentadecanoic acid with serial single-photon emission tomography

The utility of myocardial imaging and assessment of regional myocardial metabolism of omega-(123I-paraphenyl-)pentadecanoic acid (I-PPA) by means of serial single-photon tomography is demonstrated in animal experiments. High quality cross sectional images of dog hearts with clear delineation of left ventricular walls are obtained. Myocardial infarcts are visualized as areas of deficient radioactivity uptake. I-PPA elimination from non-infarcted myocardial regions is significantly (p less than 0.001) prolonged when compared with unaffected controls. Hence, not only localized absence of uptake of free fatty acid by infarcted myocardium can be demonstrated with serial single-photon tomography but also general impairment of cardiac FFA-metabolism.     

Magnetization transfer short inversion time inversion recovery enhanced 1H MRI of the human lung

The unique characteristics of the human lung arising from low proton density and multiple air-tissue interfaces of the alveoli cause difficulty in¹H lung magnetic resonance imaging. In addition, the dominating signal from sources such as the thoracic muscle and subcutaneous fat hampers the visualization of the lung parenchyma. In this contribution, an efficient tissue suppression technique is presented which allows one to significantly enhance lung parenchyma visibility. A short inversion time inversion recovery (STIR) experiment combined with a magnetization transfer (MT) experiment was used for magnetization preparation in order to suppress the signal from muscle. A half-Fourier single-shot turbo spin-echo sequence was used as acquisition module. This approach was used to perform lung anatomical imaging in eight healthy human subjects and five patients withcystic fibrosis. The results obtained demonstrate that with MT-STIR approach high quality human lung images can be obtained and that this approach has the potential for the evaluation of lung pathologies.     

High-throughput battery materials testing based on test cell arrays and dispense/jet printed electrodes

A cost effective and reliable technology for the fabrication of electrochemical test-cell arrays for battery materials research, based on batch-fabricated glass micro packages was developed and tested. Jet dispensing was investigated for the first time as a process for fabricating battery electrode arrays and separators and compared to micro dispense printing. The process shows the reproducibility over the whole range of investigated materials and battery cell structures that is required for battery materials research. Such setup gives rise to a significantly improved reliability and reproducibility of electrochemical experiments. Cost-effective fabrication of our test chips by batch processing allows for their single-use in electrochemical experiments, thereby preventing contamination issues due to repeated use as in conventional laboratory test cells. In addition, the integration of micro pseudo reference electrodes is demonstrated. Thus, the test cell array together with the developed electrode/electrolyte deposition technology provide a highly efficient tool for speedy combinatorial and high throughput testing of battery materials on a system level (full cell tests). Experimental results are shown for the microfabrication of lithium-ion test cells with help of several electrode and binder materials. The influence of jetting parameters on electrode lateral dimensions and thickness, reproducibility of the electrode mass as well as the use of integrated micro-reference electrodes for impedance spectroscopy and cyclic voltammetry measurements in micro cells are presented in detail.

     

UBET analysis of the closed-pass ring rolling of rings having arbitrarily shaped profiles

A simple but effective upper-bound elemental technique (UBET) for prediction of the torque and the deformation pattern during the ring-rolling of rings having arbitrarily shaped profiles is proposed. In order to describe the three-dimensional material flow of profile ring rolling, a new element with a curvilinear side is introduced and the corresponding kinematically admissible velocity field is derived. Upper-bound analysis is carried out for rolling rings with a circular groove or protrusion having a round corner fillet. Comparing with the experimental results, the roll torque and the profile formation are predicted with reasonable accuracy. The effects of some parameters are investigated also. Despite the simplifying assumptions, some aspects of the deformation mechanics in profile ring rolling are shown to be described successfully by the proposed method.     

Changes in RBE of 14-MeV (d + T) neutrons for V79 cells irradiated in air and in a phantom: is RBE enhanced near the surface?

PURPOSE: The relative biological effectiveness (RBE) for inactivation of V79 cells was determined as function of dose at the Heidelberg 14-MeV (d + T) neutron therapy facility after irradiation with single doses in air and at different depths in a therapy phantom. Furthermore, to assess the reproducibility of RBE determinations in different experiments we examined the relationship between the interexperimental variation in radiosensitivity towards neutrons with that towards low LET 60Co photons. METHODS: Clonogenic survival of V79 cells was determined using the colony formation assay. The cells were irradiated in suspension in small volumes (1.2 ml) free in air or at defined positions in the perspex phantom. Neutron doses were in the range, Dt = 0.5-4 Gy. 60Co photons were used as reference radiation. RESULTS: The radiosensitivity towards neutrons varied considerably less between individual experiments than that towards photons and also less than RBE. However, the mean sensitivity of different series was relatively constant. RBE increased with decreasing dose per fraction from RBE = 2.3 at 4 Gy to RBE = 3.1 at 0.5 Gy. No significant difference in RBE could be detected between irradiation at 1.6 cm and 9.4 cm depth in the phantom. However, an approximately 20% higher RBE was found for irradiation free in air compared with inside the phantom. Combining the two effects, irradiation with 0.5 Gy free in air yielded an approximately 40% higher RBE than a dose of 2 Gy inside the phantom. CONCLUSION: The measured values of RBE as function of dose per fraction within the phantom is consistent with the energy of the neutron beam. The increased RBE free in air, however, is greater than expected from microdosimetric parameters of the beam and may be due to slow recoil protons produced by interaction of multiply scattered neutrons or to an increased contribution of alpha particles from C(n, alpha) reactions near the surface. An enhanced RBE in subcutaneous layers of skin combined with an increase in RBE at low doses per fraction outside the target volume could potentially have significant consequences for normal tissue reactions in radiotherapy patients treated with fast neutrons.     

Dynamic optimal experimental design yields marginal improvement over steady‐state results for computational maximisation of regulatory T‐cell induction in ex vivo culture

The isolation of T cells, followed by differentiation into Regulatory T cells (Tregs), and re‐transplantation into the body has been proposed as a therapeutic option for inflammatory bowel disease. A key requirement for making this a viable therapeutic option is the generation of a large population of Tregs. However, cytokines in the local microenvironment can impact the yield of Tregs during differentiation. As such, experimental design is an essential part of evaluating the importance of different cytokine concentrations for Treg differentiation. However, currently only single, constant concentrations of the cytokines have been investigated. This work addresses this point by performing experimental design in silico which seeks to maximize the predicted induction of Tregs relative to Th17 cells, by selecting an optimal input function for the concentrations of TGF‐β, IL‐2, IL‐6, and IL‐23. While this approach sounds promising, the results show that only marginal improvements in the concentration of Tregs can be achieved for dynamic cytokine profiles as compared to optimal constant concentrations. Since constant concentrations are easier to implement in experiments, it is recommended for this particular system to keep the concentrations constant where IL‐6 should be kept low and high concentrations of TGF‐β, IL‐2, and IL‐23 should be used.Inspec keywords: patient treatment, molecular biophysics, proteins, cellular biophysics, diseasesOther keywords: Tregs relative, optimal input function, dynamic cytokine profiles, optimal constant concentrations, IL‐23, computational maximisation, regulatory T‐cell induction, inflammatory bowel disease, viable therapeutic option, local microenvironment, Treg differentiation, single concentrations, predicted induction, dynamic optimal experimental design, interleukin‐2, IL‐6, transforming growth factor‐β     

Magnetophoretic immunoassay of allergen-specific IgE in an enhanced magnetic field gradient

We demonstrate a novel magnetophoretic immunoassay of allergen-specific immunoglobulin E (IgE) based on the magnetophoretic deflection velocity of a microbead that is proportional to the associated magnetic nanoparticles under enhanced magnetic field gradient in a microchannel. In this detection scheme, two types of house dust mites, Dermatophagoides farinae (D. farinae) and Dermatophagoides pteronyssinus (D. pteronyssinus), were used as the model allergens. Polystyrene microbeads were conjugated with each of the mite extracts followed by incubation with serum samples. The resulting mixture was then reacted with magnetic nanoparticle-conjugated anti-human IgE for detection of allergen-specific IgE by using sandwich immuno-reactions. A ferromagnetic microstructure combined with a permanent magnet was employed to increase the magnetic field gradient ( approximately 10(4) T/m) in a microfluidic device. The magnetophoretic velocities of microbeads were measured in a microchannel under applied magnetic field, and the averaged velocity was well correlated with the concentration of allergen-specific IgE in serum. From the analysis of pooled sera obtained from 44 patients, the detection limits of the allergen-specific human IgEs for D. farinae and D. pteronyssinus were determined to be 565 (0.045 IU/mL) and 268 fM (0.021 IU/mL), respectively. These values are 1 order of magnitude lower than those by a conventional CAP system. For evaluation of reproducibility and accuracy, unknown sera were subjected to a blind test by using the developed assay system, and they were compared with the CAP system. As a result, coefficient of variance was less than 10%, and the developed method enabled a fast assay with a tiny amount of serum ( approximately 10 microL).     

Noninvasive Transdermal Vaccination Using Hyaluronan Nanocarriers and Laser Adjuvant

Vaccines are commonly administered by injection using needles. Although transdermal microneedles are less invasive promising alternatives, needle‐free topical vaccination without involving physical damage to the natural skin barrier is still sought after as it can further reduce needle‐induced anxiety and is simple to administer. However, this long‐standing goal has been elusive since the intact skin is impermeable to most macromolecules. Here, we show an efficient, noninvasive transdermal vaccination by employing two key innovations: the use of hyaluronan (HA) as vaccine carriers and non‐ablative laser adjuvants. Conjugates of a model vaccine ovalbumin (OVA) and HA—HA–OVA conjugates—induced more effective maturation of dendritic cells in vitro, compared to OVA. Following topical administration in the skin, HA–OVA conjugates penetrated into the epidermis and dermis in murine and porcine skins, as revealed by intravital microscopy and fluorescence assay. Topical administration of HA‐OVA conjugates significantly elevated both humoral and mucosal antibodies, with peak levels at four weeks. An OVA challenge at week eight elicited strong immune‐recall responses. With pretreatment of the skin using non‐ablative fractional laser beams as adjuvant, strong immunization was achieved with much reduced doses of HA–OVA (1 mg kg^–1 OVA). Our results demonstrate the potential of the noninvasive patch‐type transdermal vaccination platform.     

A lumped-parameter model to investigate the effect of plantar pressure on arterial blood flow in a diabetic foot

This paper presents a lumped-parameter model for the big-toe region that investigates the effect of plantar pressure on the diameter of the blood vessels, specifically the arteries, in the presence of arterial and/or tissue changes. The model developed in this paper uses a multi-domain energy system approach to develop the lumped-parameter differential equations. Blood flow is modelled as fluidic flow through compliant pipes that have inertia, stiffness, and damping. The tissue material is treated as a soft compliant material that transmits the external force to the blood vessels. Conclusions have been drawn to show the effect of plantar pressure, tissue damage, and their combination on the diameter of the blood vessels. The principles used here can be used to model the entire foot and the model used to investigate the effect of plantar pressure, tissue damage, and arterial changes on different parts of the foot. The work presented here may also have applications in other vascular diseases.