Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2-3% of the range, uncertainties that are contributing to an increase of the necessary planning margins added to the target volume in a patient. Imaging methods and modalities, such as Dual Energy CT and proton CT, have come into consideration in the pursuit of obtaining an as good as possible estimate of the proton stopping power. In this study, a Digital Tracking Calorimeter is benchmarked for proof-of-concept for proton CT purposes. The Digital Tracking Calorimeteris applied for reconstruction of the tracks and energies of individual high energy protons. The presented prototype forms the basis for a proton CT system using a single technology for tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter. Data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used to in order to develop a tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. The range of the individual protons can at present be estimated with a resolution of 4%. The readout system for this prototype is able to handle an effective proton frequency of 1 MHz by using 500 concurrent proton tracks in each readout frame, which is at the high end range of present similar prototypes. A future further optimized prototype will enable a high-speed and more accurate determination of the ranges of individual protons in a therapeutic beam.Comment: 21 pages, 8 figure

Photodiode read-out of the ALICE photon spectrometer PbWO4PbWO_{4} crystals

Proposal of abstract for LEB99, Snowmass, Colorado, 20-24 September 1999The PHOton Spectrometer of the ALICE experiment is an electromagnetic calorimeter of high granularity consisting of 17280 lead-tungstate (PWO) crystals of dimensions 22x22x180 mm3, read out by large-area PIN-diodes with very low-noise front-end electronics. The crystal assembly is operated at -25C to increase the PWO light yield. A 16.1x17.1 mm2 photodiode, optimized for the PWO emissio spectrum at 400-500 nm, has been developed. The 20x20 mm2 preamplifier PCB is attached to the back side of the diode ceramic frame. The charge sensitive preamplifier is built in discrete logic with two input JFETs for optimum matching with the ~150pF PIN-diode. A prototype shaper has been designed and built in discrete logic. For a detector matrix of 64 units the measured ENCs are between 450-550e at -25C. Beam tests demonstrate that the required energy resolution is reached.Summary:The PHOton Spectrometer of the ALICE experiment is an electromagnetic calorimeter of high granularity consisting of 17280 lead-tungstate (PWO) crystals of dimensions 22x22x180 mm3, coupled to large-area PIN-diodes with matching low-noise preamplifiers. PHOS is optimized for measuring photons, pi0s and eta mesons in the momentum ranges 0.5-10, 1-10 and 2-10 GeV/c, respectively, and is designed for the expected large number of particles that will be produced in central Pb-Pb collisions. Lead tungstate (PWO) is a fast scintillating crystal with a rather complex emission spectrum, consisting of two components: a blue component peaking at 420 nm and a green component peaking at 480-520 nm. The light yield of PWO at room temperature is low compared with other heavy scintillating crystals, for instance BGO. However, the yield depends strongly on the temperature with a coefficient of ~-2 degree. At the selected operating temperature of -25C the yield is about a factor of 3 higher compared to room temperature. Still, in order to reach the required energy resolution for a PHOS channel, an ENC noise of less than 600e for the PIN-diode-preamplifier-shaper stage is required. This is a very low value taking into account the high capacitance of 150-200 pF of the large area PIN-diodes. In collaboration with the PHOS project, the company AME (Horten, Norway) has designed and produced a PIN-photodiode optimized for the cross-section and spectral responsivity of the PHOS PWO crystal. The photodiode has an active area of 17.1x16.1 mm2 and is fabricated on n-type silicon material of thickness 280 um. The wafer specific resistivity is between 3000 and 6000 ohm-cm, which corresponds to a depletion voltage of 70V. The photodiode response is optimized for the spectral region 400-500 nm in order to match the PWO emission spectrum. The PIN-diode is mounted on a ceramic substrate 0.65 mm thick. On this substrate the diode is surrounded by a ceramic frame. The preamplifier PCB of dimension 20x20 mm2 is attached to the back side of the frame. The PIN-diode and bondings to ground and preamplifier input are protected by an optically transparent epoxy layer. The front side of the PIN-diode is glued onto the endface of the PWO crystal with optically transparent glue (Melt-Mount Quick-Stick, Cargille Laboratories, USA). Each crystal is wrapped in White Tyvek to ensure maximum light collection efficiency and optical insulation between the crystals. The PHOS detector consists of four independent modules, each with 4320 channels. The crystal assembly with the photo detectors are operated at -25 +/- 0.3C. The power dissipation per module is ~1 kW. The charge sensitive preamplifier is an operational amplifier built in discrete logic and with two input JFETs (BF861A). Using two JFETs in parallel gives the lowest noise for detector capacitance >100 pF. A prototype shaper, comprising three amplification stages, has been designed and built in discrete logic. For a PIN-diode with capacitance ~150 pF and a leakage current <1 nA under cooling, calculations give optimum time differentiation and integration constants around 3 microsec. For a detector matrix of 64 units the measured ENCs are between 450-550 e at -25C. Beam tests of this matrix show that the required energy resolution for the PHOS is reached

Climate change and environmental impacts on maternal and newborn health with focus on Arctic populations

In 2007, the Intergovernmental Panel on Climate Change (IPCC) presented a report on global warming and the impact of human activities on global warming. Later the Lancet commission identified six ways human health could be affected. Among these were not environmental factors which are also believed to be important for human health. In this paper we therefore focus on environmental factors, climate change and the predicted effects on maternal and newborn health. Arctic issues are discussed specifically considering their exposure and sensitivity to long range transported contaminants. Considering that the different parts of pregnancy are particularly sensitive time periods for the effects of environmental exposure, this review focuses on the impacts on maternal and newborn health. Environmental stressors known to affects human health and how these will change with the predicted climate change are addressed. Air pollution and food security are crucial issues for the pregnant population in a changing climate, especially indoor climate and food security in Arctic areas. The total number of environmental factors is today responsible for a large number of the global deaths, especially in young children. Climate change will most likely lead to an increase in this number. Exposure to the different environmental stressors especially air pollution will in most parts of the world increase with climate change, even though some areas might face lower exposure. Populations at risk today are believed to be most heavily affected. As for the persistent organic pollutants a warming climate leads to a remobilisation and a possible increase in food chain exposure in the Arctic and thus increased risk for Arctic populations. This is especially the case for mercury. The perspective for the next generations will be closely connected to the expected temperature changes; changes in housing conditions; changes in exposure patterns; predicted increased exposure to Mercury because of increased emissions and increased biological availability. A number of environmental stressors are predicted to increase with climate change and increasingly affecting human health. Efforts should be put on reducing risk for the next generation, thus global politics and research effort should focus on maternal and newborn health

The human keratins: biology and pathology

The keratins are the typical intermediate filament proteins of epithelia, showing an outstanding degree of molecular diversity. Heteropolymeric filaments are formed by pairing of type I and type II molecules. In humans 54 functional keratin genes exist. They are expressed in highly specific patterns related to the epithelial type and stage of cellular differentiation. About half of all keratins—including numerous keratins characterized only recently—are restricted to the various compartments of hair follicles. As part of the epithelial cytoskeleton, keratins are important for the mechanical stability and integrity of epithelial cells and tissues. Moreover, some keratins also have regulatory functions and are involved in intracellular signaling pathways, e.g. protection from stress, wound healing, and apoptosis. Applying the new consensus nomenclature, this article summarizes, for all human keratins, their cell type and tissue distribution and their functional significance in relation to transgenic mouse models and human hereditary keratin diseases. Furthermore, since keratins also exhibit characteristic expression patterns in human tumors, several of them (notably K5, K7, K8/K18, K19, and K20) have great importance in immunohistochemical tumor diagnosis of carcinomas, in particular of unclear metastases and in precise classification and subtyping. Future research might open further fields of clinical application for this remarkable protein family

The Bergen proton CT system

The Bergen proton Computed Tomography (pCT) is a prototype detector under construction. It aims to have the capability to track and measure ions’ energy deposition to minimize uncertainty in proton treatment planning. It is a high granularity digital tracking calorimeter, where the first two layers will act as tracking layers to obtain positional information of the incoming particle. The remainder of the detector will act as a calorimeter. Beam tests have been performed with multiple beams. These tests have shown that the ALPIDE chip sensor can measure the deposited energy, making it possible for the sensors to distinguish between the tracks in the Digital Tracking Calorimeter (DTC)

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required