Drug targeting using OX7-immunoliposomes: correlation between Thy1.1 antigen expression and tissue distribution in the rat

OX7 monoclonal antibody F((ab')2) fragments directed against Thy1.1 antigen can be used for drug targeting by coupling to the surface of drug-loaded liposomes. Such OX7-conjugated immunoliposomes (OX7-IL) were used recently for drug delivery to rat glomerular mesangial cells, which are characterized by a high level of Thy1.1 antigen expression. In the present study, the relationship between OX7-IL tissue distribution and target Thy1.1 antigen localization in different organs in rat was investigated. Western blot and immunohistofluorescence analysis revealed a very high Thy1.1 expression in brain cortex and striatum, thymus and renal glomeruli. Moderate Thy1.1 levels were observed in the collecting ducts of kidney, lung tissue and spleen. Thy1.1 was not detected in liver and heart. There was a poor correlation between Thy1.1 expression levels and organ distribution of fluorescence- or (14)C-labeled OX7-IL. The highest overall organ density of OX7-IL was observed in the spleen, followed by lung, liver and kidney. Heart and brain remained negative. With respect to intra-organ distribution, a localized and distinct signal was observed in renal glomerular mesangial cells only. As a consequence, acute pharmacological (i.e. toxic) effects of doxorubicin-loaded OX7-IL were limited to renal glomeruli. The competition with unbound OX7 monoclonal antibody F((ab')2) fragments demonstrated that the observed tissue distribution and acute pharmacological effects of OX7-IL were mediated specifically by the conjugated OX7 antibody. It is concluded that both the high target antigen density and the absence of endothelial barriers are needed to allow for tissue-specific accumulation and pharmacological effects of OX7-IL. The liposomal drug delivery strategy used is therefore specific toward renal glomeruli and can be expected to reduce the risk of unwanted side effects in other tissues.

Characterization of the dose distribution in the halo region of a clinical proton pencil beam using emulsion film detectors

Proton therapy is a high precision technique in cancer radiation therapy which allows irradiating the tumor with minimal damage to the surrounding healthy tissues. Pencil beam scanning is the most advanced dose distribution technique and it is based on a variable energy beam of a few millimeters FWHM which is moved to cover the target volume. Due to spurious effects of the accelerator, of dose distribution system and to the unavoidable scattering inside the patient's body, the pencil beam is surrounded by a halo that produces a peripheral dose. To assess this issue, nuclear emulsion films interleaved with tissue equivalent material were used for the first time to characterize the beam in the halo region and to experimentally evaluate the corresponding dose. The high-precision tracking performance of the emulsion films allowed studying the angular distribution of the protons in the halo. Measurements with this technique were performed on the clinical beam of the Gantry1 at the Paul Scherrer Institute. Proton tracks were identified in the emulsion films and the track density was studied at several depths. The corresponding dose was assessed by Monte Carlo simulations and the dose profile was obtained as a function of the distance from the center of the beam spot.

Local strain distribution in real three-dimensional alveolar geometries

Mechanical ventilation is not only a life saving treatment but can also cause negative side effects. One of the main complications is inflammation caused by overstretching of the alveolar tissue. Previously, studies investigated either global strains or looked into which states lead to inflammatory reactions in cell cultures. However, the connection between the global deformation, of a tissue strip or the whole organ, and the strains reaching the single cells lining the alveolar walls is unknown and respective studies are still missing. The main reason for this is most likely the complex, sponge-like alveolar geometry, whose three-dimensional details have been unknown until recently. Utilizing synchrotron-based X-ray tomographic microscopy, we were able to generate real and detailed three-dimensional alveolar geometries on which we have performed finite-element simulations. This allowed us to determine, for the first time, a three-dimensional strain state within the alveolar wall. Briefly, precision-cut lung slices, prepared from isolated rat lungs, were scanned and segmented to provide a three-dimensional geometry. This was then discretized using newly developed tetrahedral elements. The main conclusions of this study are that the local strain in the alveolar wall can reach a multiple of the value of the global strain, for our simulations up to four times as high and that thin structures obviously cause hotspots that are especially at risk of overstretching.

Comparison of brain PrPd distribution in ovine BSE and scrapie

Scrapie and bovine spongiform encephalopathy (BSE) are both prion diseases affecting ruminants, and these diseases do not share the same public health concerns. Surveillance of the BSE agent in small ruminants has been a great challenge, and the recent identification of diverse prion diseases in ruminants has led to the development of new methods for strain typing. In our study, using immunohistochemistry (IHC), we assessed the distribution of PrP(d) in the brains of 2 experimentally BSE-infected sheep with the ARQ/ARQ genotype. Distribution of PrP(d) in the brain, from the spinal cord to the frontal cortex, was remarkably similar in the 2 sheep despite different inoculation routes and incubation periods. Comparatively, overall PrP(d) brain distribution, evaluated by IHC, in 19 scrapie cases with the ARQ/ARQ, ARQ/VRQ, and VRQ/VRQ genotypes, in some cases showed similarities to the experimentally BSE-infected sheep. There was no exclusive neuroanatomical site with a characteristic and specific PrP(d) type of accumulation induced by the BSE agent. However, a detailed analysis of the topography, types, and intensity of PrP(d) deposits in the frontal cortex, striatum, piriform cortex, hippocampus, mesencephalon, and cerebellum allowed the BSE-affected sheep group to be distinguished from the 19 scrapie cases analyzed in our study. These results strengthen and emphasize the potential interest of PrP(d) brain mapping to help in identifying prion strains in small ruminants.

The effect of standard and low-modulus cement augmentation on the stiffness, strength, and endplate pressure distribution in vertebroplasty

Vertebroplasty restores stiffness and strength of fractured vertebral bodies, but alters their stress transfer. This unwanted effect may be reduced by using more compliant cements. However, systematic experimental comparison of structural properties between standard and low-modulus augmentation needs to be done. This study investigated how standard and low-modulus cement augmentation affects apparent stiffness, strength, and endplate pressure distribution of vertebral body sections.

Haptics in forensics: the possibilities and advantages in using the haptic device for reconstruction approaches in forensic science

Non-invasive documentation methods such as surface scanning and radiological imaging are gaining in importance in the forensic field. These three-dimensional technologies provide digital 3D data, which are processed and handled in the computer. However, the sense of touch gets lost using the virtual approach. The haptic device enables the use of the sense of touch to handle and feel digital 3D data. The multifunctional application of a haptic device for forensic approaches is evaluated and illustrated in three different cases: the representation of bone fractures of the lower extremities, by traffic accidents, in a non-invasive manner; the comparison of bone injuries with the presumed injury-inflicting instrument; and in a gunshot case, the identification of the gun by the muzzle imprint, and the reconstruction of the holding position of the gun. The 3D models of the bones are generated from the Computed Tomography (CT) images. The 3D models of the exterior injuries, the injury-inflicting tools and the bone injuries, where a higher resolution is necessary, are created by the optical surface scan. The haptic device is used in combination with the software FreeForm Modelling Plus for touching the surface of the 3D models to feel the minute injuries and the surface of tools, to reposition displaced bone parts and to compare an injury-causing instrument with an injury. The repositioning of 3D models in a reconstruction is easier, faster and more precisely executed by means of using the sense of touch and with the user-friendly movement in the 3D space. For representation purposes, the fracture lines of bones are coloured. This work demonstrates that the haptic device is a suitable and efficient application in forensic science. The haptic device offers a new way in the handling of digital data in the virtual 3D space.

Analysis of the 207Bi, 194Hg/Au and 173Lu distribution in the irradiated MEGAPIE target

Samples obtained from different locations within the prototype liquid metal spallation target MEGAPIE irradiated in 2006 at PSI were analysed using γ-spectrometry. A variety of radionuclides formed by reaction of the target material, lead–bismuth eutectic (LBE), with the proton beam and secondary particles were identified. While nuclides representing the target material itself (207Bi) and nuclides of noble metals were found in LBE samples throughout the target, nuclides of electropositive metals were found to be quantitatively deposited on free surfaces and material interfaces within the target system. This behaviour is analysed in more detail based on results obtained for three nuclides representing groups of elements with distinct chemical behaviour, namely 207Bi, 194Hg/Au and 173Lu. Quantitative analysis results are given and compared with predictions obtained using nuclear physics calculations for those nuclides showing rather homogeneous distribution within the target. Possible reasons for the separation of radionuclides from the liquid metal and their deposition on surfaces are given, and consequences arising for nuclear facilities utilizing liquid metals are discussed.

Measurement of the Z/ѵ* boson transverse momentum distribution in pp collisions at √s = 7 TeV with the ATLAS detector

This paper describes a measurement of the Z/ѵ* boson transverse momentum spectrum using ATLAS proton-proton collision data at a centre-of-mass energy of √s = 7 TeV at the LHC. The measurement is performed in the Z/ѵ* → e+e− and Z/ѵ* → μ+μ− channels, using data corresponding to an integrated luminosity of 4.7 fb−1. Normalized differential cross sections as a function of the Z/ѵ* boson transverse momentum are measured for transverse momenta up to 800 GeV. The measurement is performed inclusively for Z/ѵ* rapidities up to 2.4, as well as in three rapidity bins. The channel results are combined, compared to perturbative and resummed QCD calculations and used to constrain the parton shower parameters of Monte Carlo generators.

Effect of the Tiger Stripes on the water vapor distribution in Enceladus' exosphere

The jet activity emanating from Enceladus' exosphere south pole region observed by Cassini is a subject of intensive study. The in situ and remote sensing observations performed since 2005 triggered an active modeling campaign. Such modeling is essential for better understanding of the measurements performed by individual instruments as well as to link them for a more complete picture of the volatile and ice grain distribution in Enceladus' exosphere. This paper is focused on the investigation of the effect that diffuse gas sources along the Tiger Stripes have on distribution of the water vapor in Enceladus' exosphere using the updated version of our multiplume model. We have found that accounting for the gas production by Tiger Stripes is critical for interpretation of the Cassini data. According to our calculations, sources along the Tiger Stripes (apart from those originally identified by Spitale and Porco (2007)) must contribute about 23–32% to the total plume source rate, which varies in the range of (6.4–29) ×1027 s−1. The effect of the previously unidentified source suggested in the paper is found to be critical for explaining the Ultraviolet Imaging Spectrograph 2007 and 2010 observations in the whole range of the elapsed times.

Adiponectin isoform distribution in serum and in follicular fluid of women undergoing treatment by ICSI

Adiponectin is an adipokine, present in the circulation in comparatively high concentrations and different molecular weight isoforms. For the first time, the distribution of these isoforms in serum and follicular fluid (FF) and their usefulness as biological markers for infertility investigations was studied.

Embedding Spatial Software Visualization in the IDE: an Exploratory Study

Software visualization can be of great use for understanding and exploring a software system in an intuitive manner. Spatial representation of software is a promising approach of increasing interest. However, little is known about how developers interact with spatial visualizations that are embedded in the IDE. In this paper, we present a pilot study that explores the use of Software Cartography for program comprehension of an unknown system. We investigated whether developers establish a spatial memory of the system, whether clustering by topic offers a sound base layout, and how developers interact with maps. We report our results in the form of observations, hypotheses, and implications. Key findings are a) that developers made good use of the map to inspect search results and call graphs, and b) that developers found the base layout surprising and often confusing. We conclude with concrete advice for the design of embedded software maps

dGEMRIC and subsequent T1 mapping of the hip at 1.5 Tesla: normative data on zonal and radial distribution in asymptomatic volunteers

To characterize the zonal distribution of three-dimensional (3D) T1 mapping in the hip joint of asymptomatic adult volunteers.