The APSEL4D Monolithic Active Pixel Sensor and its Usage in a Single Electron Interference Experiment

We have realized a Data Acquisition chain for the use and characterization of APSEL4D, a 32 x 128 Monolithic Active Pixel Sensor, developed as a prototype for frontier experiments in high energy particle physics. In particular a transition board was realized for the conversion between the chip and the FPGA voltage levels and for the signal quality enhancing. A Xilinx Spartan-3 FPGA was used for real time data processing, for the chip control and the communication with a Personal Computer through a 2.0 USB port. For this purpose a firmware code, developed in VHDL language, was written. Finally a Graphical User Interface for the online system monitoring, hit display and chip control, based on windows and widgets, was realized developing a C++ code and using Qt and Qwt dedicated libraries. APSEL4D and the full acquisition chain were characterized for the first time with the electron beam of the transmission electron microscope and with 55Fe and 90Sr radioactive sources. In addition, a beam test was performed at the T9 station of the CERN PS, where hadrons of momentum of 12 GeV/c are available. The very high time resolution of APSEL4D (up to 2.5 Mfps, but used at 6 kfps) was fundamental in realizing a single electron Young experiment using nanometric double slits obtained by a FIB technique. On high statistical samples, it was possible to observe the interference and diffractions of single isolated electrons traveling inside a transmission electron microscope. For the first time, the information on the distribution of the arrival time of the single electrons has been extracted.

Untersuchungen zur Strahldynamik am Harmonischen Doppelseitigen Mikrotron von MAMI-C

Das Institut für Kernphysik der Universität Mainz betreibt seit 1990 eine weltweit einzigartige Beschleunigeranlage für kern- und teilchenphysikalische Experimente – das Mainzer Mikrotron (MAMI-B). Diese Beschleunigerkaskade besteht aus drei Rennbahn-Mikrotrons (RTMs) mit Hochfrequenzlinearbeschleunigern bei 2.45 GHz, mit denen ein quasi kontinuierlicher Elektronenstrahl von bis zu 100 μA auf 855MeV beschleunigt werden kann.rnrnIm Jahr 1999 wurde die Umsetzung der letzten Ausbaustufe – ein Harmonisches Doppelseitiges Mikrotron (HDSM, MAMI-C) – mit einer Endenergie von 1.5 GeV begonnen. Die Planung erforderte einige mutige Schritte, z.B. Umlenkmagnete mit Feldgradient und ihren daraus resultierenden strahloptischen Eigenschaften, die einen großen Einfluss auf die Longitudinaldynamik des Beschleunigers haben. Dies erforderte die Einführung der „harmonischen“ Betriebsweise mit zwei Frequenzen der zwei Linearbeschleuniger.rnrnViele Maschinenparameter (wie z.B. HF-Amplituden oder -Phasen) wirken direkt auf den Beschleunigungsprozess ein, ihre physikalischen Größen sind indes nicht immer auf einfache Weise messtechnisch zugänglich. Bei einem RTM mit einer verhältnismäßig einfachen und wohldefinierten Strahldynamik ist das im Routinebetrieb unproblematisch, beim HDSM hingegen ist schon allein wegen der größeren Zahl an Parametern die Kenntnis der physikalischen Größen von deutlich größerer Bedeutung. Es gelang im Rahmen dieser Arbeit, geeignete Methoden der Strahldiagnose zu entwickeln, mit denen diese Maschinenparameter überprüft und mit den Planungsvorgaben verglichen werden können.rnrnDa die Anpassung des Maschinenmodells an eine einzelne Phasenmessung aufgrund der unvermeidlichen Messfehler nicht immer eindeutige Ergebnisse liefert, wird eine Form der Tomographie verwendet. Der longitudinale Phasenraum wird dann in Form einer Akzeptanzmessung untersucht. Anschließend kann ein erweitertes Modell an die gewonnene Datenvielfalt angepasst werden, wodurch eine größere Signifikanz der Modellparameter erreicht wird.rnrnDie Ergebnisse dieser Untersuchungen zeigen, dass sich der Beschleuniger als Gesamtsystem im Wesentlichen wie vorhergesagt verhält und eine große Zahl unterschiedlicher Konfigurationen zum Strahlbetrieb möglich sind – im Routinebetrieb wird dies jedoch vermieden und eine bewährte Konfiguration für die meisten Situationen eingesetzt. Das führt zu einer guten Reproduzierbarkeit z.B. der Endenergie oder des Spinpolarisationswinkels an den Experimentierplätzen.rnrnDie Erkenntnisse aus diesen Untersuchungen wurden teilweise automatisiert, so dass nun den Operateuren zusätzliche und hilfreiche Diagnose zur Verfügung steht, mit denen der Maschinenbetrieb noch zuverlässiger durchgeführt werden kann.

Generalized eMC implementation for Monte Carlo dose calculation of electron beams from different machine types

The electron Monte Carlo (eMC) dose calculation algorithm available in the Eclipse treatment planning system (Varian Medical Systems) is based on the macro MC method and uses a beam model applicable to Varian linear accelerators. This leads to limitations in accuracy if eMC is applied to non-Varian machines. In this work eMC is generalized to also allow accurate dose calculations for electron beams from Elekta and Siemens accelerators. First, changes made in the previous study to use eMC for low electron beam energies of Varian accelerators are applied. Then, a generalized beam model is developed using a main electron source and a main photon source representing electrons and photons from the scattering foil, respectively, an edge source of electrons, a transmission source of photons and a line source of electrons and photons representing the particles from the scrapers or inserts and head scatter radiation. Regarding the macro MC dose calculation algorithm, the transport code of the secondary particles is improved. The macro MC dose calculations are validated with corresponding dose calculations using EGSnrc in homogeneous and inhomogeneous phantoms. The validation of the generalized eMC is carried out by comparing calculated and measured dose distributions in water for Varian, Elekta and Siemens machines for a variety of beam energies, applicator sizes and SSDs. The comparisons are performed in units of cGy per MU. Overall, a general agreement between calculated and measured dose distributions for all machine types and all combinations of parameters investigated is found to be within 2% or 2 mm. The results of the dose comparisons suggest that the generalized eMC is now suitable to calculate dose distributions for Varian, Elekta and Siemens linear accelerators with sufficient accuracy in the range of the investigated combinations of beam energies, applicator sizes and SSDs.

Dosimetric properties of an amorphous silicon EPID for verification of modulated electron radiotherapy

Purpose: To investigate the dosimetric properties of an electronic portal imaging device (EPID) for electron beam detection and to evaluate its potential for quality assurance (QA) of modulated electron radiotherapy (MERT). Methods: A commercially available EPID was used to detect electron beams shaped by a photon multileaf collimator (MLC) at a source-surface distance of 70 cm. The fundamental dosimetric properties such as reproducibility, dose linearity, field size response, energy response, and saturation were investigated for electron beams. A new method to acquire the flood-field for the EPID calibration was tested. For validation purpose, profiles of open fields and various MLC fields (square and irregular) were measured with a diode in water and compared to the EPID measurements. Finally, in order to use the EPID for QA of MERT delivery, a method was developed to reconstruct EPID two-dimensional (2D) dose distributions in a water-equivalent depth of 1.5 cm. Comparisons were performed with film measurement for static and dynamic monoenergy fields as well as for multienergy fields composed by several segments of different electron energies. Results: The advantageous EPID dosimetric properties already known for photons as reproducibility, linearity with dose, and dose rate were found to be identical for electron detection. The flood-field calibration method was proven to be effective and the EPID was capable to accurately reproduce the dose measured in water at 1.0 cm depth for 6 MeV, 1.3 cm for 9 MeV, and 1.5 cm for 12, 15, and 18 MeV. The deviations between the output factors measured with EPID and in water at these depths were within ±1.2% for all the energies with a mean deviation of 0.1%. The average gamma pass rate (criteria: 1.5%, 1.5 mm) for profile comparison between EPID and measurements in water was better than 99% for all the energies considered in this study. When comparing the reconstructed EPID 2D dose distributions at 1.5 cm depth to film measurements, the gamma pass rate (criteria: 2%, 2 mm) was better than 97% for all the tested cases. Conclusions: This study demonstrates the high potential of the EPID for electron dosimetry, and in particular, confirms the possibility to use it as an efficient verification tool for MERT delivery.

3D visualization of HIV virions by cryoelectron tomography.

The structure of the human immunodeficiency virus (HIV) and some of its components have been difficult to study in three-dimensions (3D) primarily because of their intrinsic structural variability. Recent advances in cryoelectron tomography (cryo-ET) have provided a new approach for determining the 3D structures of the intact virus, the HIV capsid, and the envelope glycoproteins located on the viral surface. A number of cryo-ET procedures related to specimen preservation, data collection, and image processing are presented in this chapter. The techniques described herein are well suited for determining the ultrastructure of bacterial and viral pathogens and their associated molecular machines in situ at nanometer resolution.

High-density large-scale field emitter arrays for x-ray free electron laser cathodes

High brightness electron sources are of great importance for the operation of the hard X-ray free electron lasers. Field emission cathodes based on the double-gate metallic field emitter arrays (FEAs) can potentially offer higher brightness than the currently used ones. We report on the successful application of electron beam lithography for fabrication of the large-scale single-gate as well as double-gate FEAs. We demonstrate operational high-density single-gate FEAs with sub-micron pitch and total number of tips up to 106 as well as large-scale double-gate FEAs with large collimation gate apertures. The details of design, fabrication procedure and successful measurements of the emission current from the single- and double-gate cathodes are presented.

Forward treatment planning for modulated electron radiotherapy (MERT) employing Monte Carlo methods

PURPOSE This paper describes the development of a forward planning process for modulated electron radiotherapy (MERT). The approach is based on a previously developed electron beam model used to calculate dose distributions of electron beams shaped by a photon multi leaf collimator (pMLC). METHODS As the electron beam model has already been implemented into the Swiss Monte Carlo Plan environment, the Eclipse treatment planning system (Varian Medical Systems, Palo Alto, CA) can be included in the planning process for MERT. In a first step, CT data are imported into Eclipse and a pMLC shaped electron beam is set up. This initial electron beam is then divided into segments, with the electron energy in each segment chosen according to the distal depth of the planning target volume (PTV) in beam direction. In order to improve the homogeneity of the dose distribution in the PTV, a feathering process (Gaussian edge feathering) is launched, which results in a number of feathered segments. For each of these segments a dose calculation is performed employing the in-house developed electron beam model along with the macro Monte Carlo dose calculation algorithm. Finally, an automated weight optimization of all segments is carried out and the total dose distribution is read back into Eclipse for display and evaluation. One academic and two clinical situations are investigated for possible benefits of MERT treatment compared to standard treatments performed in our clinics and treatment with a bolus electron conformal (BolusECT) method. RESULTS The MERT treatment plan of the academic case was superior to the standard single segment electron treatment plan in terms of organs at risk (OAR) sparing. Further, a comparison between an unfeathered and a feathered MERT plan showed better PTV coverage and homogeneity for the feathered plan, with V95% increased from 90% to 96% and V107% decreased from 8% to nearly 0%. For a clinical breast boost irradiation, the MERT plan led to a similar homogeneity in the PTV compared to the standard treatment plan while the mean body dose was lower for the MERT plan. Regarding the second clinical case, a whole breast treatment, MERT resulted in a reduction of the lung volume receiving more than 45% of the prescribed dose when compared to the standard plan. On the other hand, the MERT plan leads to a larger low-dose lung volume and a degraded dose homogeneity in the PTV. For the clinical cases evaluated in this work, treatment plans using the BolusECT technique resulted in a more homogenous PTV and CTV coverage but higher doses to the OARs than the MERT plans. CONCLUSIONS MERT treatments were successfully planned for phantom and clinical cases, applying a newly developed intuitive and efficient forward planning strategy that employs a MC based electron beam model for pMLC shaped electron beams. It is shown that MERT can lead to a dose reduction in OARs compared to other methods. The process of feathering MERT segments results in an improvement of the dose homogeneity in the PTV.

The electron optical limits of performance of single-polepiece magnetic electron lenses

The thesis is concerned with the electron properties of single-polepiece magnetic electron lenses especially under conditions of extreme polepiece saturation. The electron optical properties are first analysed under conditions of high polepiece permeability. From this analysis, a general idea can be obtained of the important parameters that affect ultimate lens performance. In addition, useful information is obtained concerning the design of improved lenses operating under conditions of extreme polepiece saturation, for example at flux densities of the order of 10 Tesla. It is shown that in a single-polepiece lens , the position and shape of the lens exciting coil plays an important role. In particular, the maximum permissible current density in the windings,rather than the properties of the iron, can set a limit to lens performance. This factor was therefore investigated in some detail. The axial field distribution of a single-polepiece lens, unlike that of a conventional lens, is highly asymmetrical. There are therefore two possible physical arrangements of the lens with respect to the incoming electron beam. In general these two orientations will result in different aberration coefficients. This feature has also been investigated in some detail. Single-pole piece lenses are thus considerably more complicated electron- optically than conventional double polepiece lenses. In particular, the absence of the usual second polepiece causes most of the axial magnetic flux density distribution to lie outside the body of the lens. This can have many advantages in electron microscopy but it creates problems in calculating the magnetic field distribution. In particular, presently available computer programs are liable to be considerably in error when applied to such structures. It was therefore necessary to find independent ways of checking the field calculations. Furthermore, if the polepiece is allowed to saturate, much more calculation is involved since the field distribution becomes a non-linear function of the lens excitation. In searching for optimum lens designs, care was therefore taken to ensure that the coil was placed in the optimum position. If this condition is satisfied there seems to be no theoretical limit to the maximum flux density that can be attained at the polepiece tip. However , under iron saturation condition, some broadening of the axial field distribution will take place, thereby changing the lens aberrations . Extensive calculations were therefore made to find the minimum spherical and chromatic aberration coefficients . The focal properties of such lens designs are presented and compared with the best conventional double-polepiece lenses presently available.

Experimental Study of Storage Ring Free-Electron Laser with Novel Capabilities

The Duke Free-electron laser (FEL) system, driven by the Duke electron storage ring, has been at the forefront of developing new light source capabilities over the past two decades. In 1999, the Duke FEL demonstrated the first lasing of a storage ring FEL in the vacuum ultraviolet (VUV) region at $194$ nm using two planar OK-4 undulators. With two helical undulators added to the outboard sides of the planar undulators, in 2005 the highest FEL gain ($47.8\%$) of a storage ring FEL was achieved using the Duke FEL system with a four-undulator configuration. In addition, the Duke FEL has been used as the photon source to drive the High Intensity $\gamma$-ray Source (HIGS) via Compton scattering of the FEL beam and electron beam inside the FEL cavity. Taking advantage of FEL's wavelength tunability as well as the adjustability of the energy of the electron beam in the storage ring, the nearly monochromatic $\gamma$-ray beam has been produced in a wide energy range from $1$ to $100$ MeV at the HIGS. To further push the FEL short wavelength limit and enhance the FEL gain in the VUV regime for high energy $\gamma$-ray production, two additional helical undulators were installed in 2012 using an undulator switchyard system to allow switching between the two planar and two helical undulators in the middle section of the FEL system. Using different undulator configurations made possible by the switchyard, a number of novel capabilities of the storage ring FEL have been developed and exploited for a wide FEL wavelength range from infrared (IR) to VUV. These new capabilities will eventually be made available to the $\gamma$-ray operation, which will greatly enhance the $\gamma$-ray user research program, creating new opportunities for certain types of nuclear physics research.

With the wide wavelength tuning range, the FEL is an intrinsically well-suited device to produce lasing with multiple colors. Taking advantage of the availability of an undulator system with multiple undulators, we have demonstrated the first two-color lasing of a storage ring FEL. Using either a three- or four-undulator configuration with a pair of dual-band high reflectivity mirrors, we have achieved simultaneous lasing in the IR and UV spectral regions. With the low-gain feature of the storage ring FEL, the power generated at the two wavelengths can be equally built up and precisely balanced to reach FEL saturation. A systematic experimental program to characterize this two-color FEL has been carried out, including precise power control, a study of the power stability of two-color lasing, wavelength tuning, and the impact of the FEL mirror degradation. Using this two-color laser, we have started to develop a new two-color $\gamma$-ray beam for scientific research at the HIGS.

Using the undulator switchyard, four helical undulators installed in the beamline can be configured to not only enhance the FEL gain in the VUV regime, but also allow for the full polarization control of the FEL beams. For the accelerator operation, the use of helical undulators is essential to extend the FEL mirror lifetime by reducing radiation damage from harmonic undulator radiation. Using a pair of helical undulators with opposite helicities, we have realized (1) fast helicity switching between left- and right-circular polarizations, and (2) the generation of fully controllable linear polarization. In order to extend these new capabilities of polarization control to the $\gamma$-ray operation in a wide energy range at the HIGS, a set of FEL polarization diagnostic systems need to be developed to cover the entire FEL wavelength range. The preliminary development of the polarization diagnostics for the wavelength range from IR to UV has been carried out.

Demonstration of passive plasma lensing of a laser wakefield accelerated electron bunch

We report on the first demonstration of passive all-optical plasma lensing using a two-stage setup. An intense femtosecond laser accelerates electrons in a laser wakefield accelerator (LWFA) to 100 MeVover millimeter length scales. By adding a second gas target behind the initial LWFAstage we introduce a robust and independently tunable plasma lens. We observe a density dependent reduction of the LWFA electron beam divergence from an initial value of 2.3 mrad, down to 1.4 mrad (rms), when the plasma lens is in operation. Such a plasma lens provides a simple and compact approach for divergence reduction well matched to the mm-scale length of the LWFA accelerator. The focusing forces are provided solely by the plasma and driven by the bunch itself only, making this a highly useful and conceptually new approach to electron beam focusing. Possible applications of this lens are not limited to laser plasma accelerators. Since no active driver is needed the passive plasma lens is also suited for high repetition rate focusing of electron bunches. Its understanding is also required for modeling the evolution of the driving particle bunch in particle driven wake field acceleration.

Asociación entre la escala de riesgo Framingham y el puntaje de calcio coronario

Introducción: Entre las diferentes herramientas clínicas para evaluar la presencia de enfermedad coronaria mediante puntajes, la más usada es la Escala de Riesgo cardiovascular de Framingham. Desde hace unos años, se creó el puntaje de calcio coronario el cual mide el riesgo cardiovascular según la presencia de placas ateromatosas vistas por tomografía computarizada. Se evaluó la asociación entre la escala de Framigham y el puntaje de calcio coronario en una población de sujetos sanos asintomáticos. Metodología: Se realizó un estudio transversal para evaluar la asociación entre el puntaje de calcio coronario y la escala de Framingham en sujetos asintomáticos que se practicaron exámen médico preventivo en la Fundación Cardioinfantil- Instituto de Cardiología (FCI-IC) en el periodo comprendido entre 1 de Julio 2011 hasta el 31 de octubre de 2015. Resultados: Se evaluaron 262 pacientes en total. La prevalencia de riesgo cardiovascular fue bajo en un 77.86% de la población, medio en 18.70% y alto en 3.44%, según la escala de Framingham. El riesgo cardiovascular según el puntaje de Calcio coronario fue nulo 70.99%, bajo en 21.75%, medio en 4.19%, severo en 3.05%. Se encontró una asociación entre ambos puntajes para riesgo estadísticamente significativa (p0,00001) Discusión: El riesgo cardiovascular establecido por escala de Framingham se relaciona de forma significativa con la presencia de placas aterioscleróticas. El estudio demostró que en una muestra de sujetos asintomáticos, hay una alteración estructural coronaria temprana.

Estudo experimental do movimento de partículas carregadas em campos elétricos e magnéticos: seletor de velocidades

Neste trabalho é apresentado um experimento incluído no contexto de experimentos longos adotado nas disciplinas experimentais de eletricidade, magnetismo e óptica, e consiste na caracterização de um seletor de velocidades que funciona com campos elétricos e magnéticos cruzados. Utiliza-se um tubo de raios catódicos para gerar um feixe de elétrons. As placas de deflexão vertical do tubo geram o campo elétrico e um par de bobinas, com os eixos perpendiculares ao eixo do tubo, gera o campo magnético. São realizados estudos de trajetória dos elétrons com auxílio de um programa de simulação de elétrons.

Gold-implanted shallow conducting layers in polymethylmethacrylate

PMMA (polymethylmethacrylate) was ion implanted with gold at very low energy and over a range of different doses using a filtered cathodic arc metal plasma system. A nanometer scale conducting layer was formed, fully buried below the polymer surface at low implantation dose, and evolving to include a gold surface layer as the dose was increased. Depth profiles of the implanted material were calculated using the Dynamic TRIM computer simulation program. The electrical conductivity of the gold-implanted PMMA was measured in situ as a function of dose. Samples formed at a number of different doses were subsequently characterized by Rutherford backscattering spectrometry, and test patterns were formed on the polymer by electron beam lithography. Lithographic patterns were imaged by atomic force microscopy and demonstrated that the contrast properties of the lithography were well maintained in the surface-modified PMMA.

Conducting polymer formed by low energy gold ion implantation

A buried conducting layer of metal/polymer nanocomposite was formed by very low energy gold ion implantation into polymethylmethacrylate. The conducting layer is similar to 3 nm deep and of width similar to 1 nm. In situ resistivity measurements were performed as the implantation proceeded, and the conductivity thus obtained as a function of buried gold concentration. The measured conductivity obeys the behavior well established for composites in the percolation regime. The critical concentration, below which the polymer remains an insulator, is attained at a dose similar to 1.0 x 10(16) atoms/cm(2) of implanted gold ions. (C) 2008 American Institute of Physics.

Cytotoxicity and Endothelial Cell Adhesion of Lyophilized and Irradiated Bovine Pericardium Modified With Silk Fibroin and Chitosan

Grafts of biological tissues have been used since the 1960s as an alternative to the mechanical heart prostheses. Nowadays, the most consolidated treatment to bovine pericardial (BP) bioprostheses is the crosslinking with glutaraldehyde (GA), although GA may induce calcification in vivo. In previous work, our group demonstrated that electron beam irradiation applied to lyophilized BP in the absence of oxygen promoted crosslinks among collagen fibers of BP tissue. In this work, the incorporation of silk fibroin (SF) and chitosan (CHIT) in the BP not treated with GA was studied. The samples were irradiated and then analyzed for their cytotoxicity and the ability of adhesion and growth of endothelial cells. Initially, all samples showed cytotoxicity. However, after a few washing cycles, the cytotoxicity due to acetic acid and ethanol residues was removed from the biomaterial making it suitable for the biofunctional test. The samples modified with SF/CHIT and electron beam irradiated favored the adhesion and growth of endothelial cells throughout the tissue.