bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO‐F‐CAMPUS‐T‐05: Design of An Innovative Beam Monitor for Particle Therapy for the Simultaneous Measurement of Beam Fluence and Energy
Authors: Sacchi R , Cartiglia N , Cenna F , Guarachi L Fanola , Ferrero M , Giordanengo S , Marchetto F , Monaco V , Vignati A , Anvar M Varasteh , Cirio R 
Published: June 2015

Purpose:Monitoring the prescribed dose in particle therapy is typically carried out by using parallel plate ionization chambers working in transmission mode. The use of gas detectors has several drawbacks: they need to be calibrated daily against standard dosimeters and their dependence on beam quality factors need to be fully characterized and controlled with high accuracy. A detector capable of single particle counting is proposed which would overcome all these limitations. Combined with a gas ionization chamber, it will allow determining the average particle stopping power, thus providing an effective method for the online verification of the selected particle energy and range.Methods:Low‐Gain Avalanche Detectors (LGADs) are innovative n‐in‐p silicon sensors with moderate internal charge multiplication occurring in the strong field generated by an additional p+ doping layer implanted at a depth of a few µm in the bulk of the sensor. The increased signal‐to‐noise ratio allows designing very thin, few tens of microns, segmented LGADs, called Ultra Fast Silicon Detectors (UFSD), optimized for very fast signal, which would be suitable for charged particle counting at high rates. A prototype UFSD is being designed for this purpose.Results:Different LGAD diodes have been characterized both in laboratory and beam tests, and the results compared both with those obtained with similar diodes without the gain layer and with a program simulating the signal in the sensors. The signal is found to be enhanced in LGADs, while the leakage current and the noise is not affected by the gain. Possible alternative designs and implementations are also presented and discussed.Conclusion:Thanks to their excellent counting capabilities, UFSD detectors are a promising technology for future beam monitor devices in hadron‐therapy applications. Studies are ongoing to better understand their properties and optimize the design in view of this application.
MO‐F‐CAMPUS‐I‐02: Occupational Conceptus Doses From Fluoroscopically‐Guided Interventional Procedures
Authors: Damilakis J , Perisinakis K , Solomou G , Stratakis J 
Published: June 2015

Purpose:The aim of this method was to provide dosimetric data on conceptus dose for the pregnant employee who participates in fluoroscopically‐guided interventional procedures.Methods:Scattered air‐kerma dose rates were obtained for 17 fluoroscopic projections involved in interventional procedures. These projections were simulated on an anthropomorphic phantom placed on the examination table supine. The operating theater was divided into two grids relative to the long table sides. Each grid consisted of 33 cells spaced 0.50 m apart. During the simulated exposures, at each cell, scatter air‐kerma rate was measured at 110 cm from the floor i.e. at the height of the waist of the pregnant worker. Air‐kerma rates were divided by the dose area product (DAP) rate of each exposure to obtain normalized data. For each projection, measurements were performed for 3 kVp and 3 filtration values i.e. for 9 different x‐ray spectra. All measurements were performed by using a modern C‐arm angiographic system (Siemens Axiom Artis, Siemens, Germany) and a radiation meter equipped with an ionization chamber.Results:The results consist of 153 iso‐dose maps, which show the spatial distribution of DAP‐normalized scattered air‐kerma doses at the waist level of a pregnant worker. Conceptus dose estimation is possible using air‐kerma to embryo/fetal dose conversion coefficients published in a previous study (J Cardiovasc Electrophysiol, Vol. 16, pp. 1–8, July 2005). Using these maps, occupationally exposed pregnant personnel may select a working position for a certain projection that keeps abdominal dose as low as reasonably achievable. Taking into consideration the regulatory conceptus dose limit for occupational exposure, determination of the maximum workload allowed for the pregnant personnel is also possible.Conclusion:Data produced in this work allow for the anticipation of conceptus dose and the determination of the maximum workload for a pregnant worker from any fluoroscopically‐guided interventional procedure.This study was supported by the Greek Ministry of Education and Religious Affairs, General Secretariat for Research and Technology, Operational Program ‘Education and Lifelong Learning’, ARISTIA (Research project: CONCERT).
TU‐AB‐BRD‐03: Fault Tree Analysis
Authors: Dunscombe P. 
Published: June 2015

Current quality assurance and quality management guidelines provided by various professional organizations are prescriptive in nature, focusing principally on performance characteristics of planning and delivery devices. However, published analyses of events in radiation therapy show that most events are often caused by flaws in clinical processes rather than by device failures. This suggests the need for the development of a quality management program that is based on integrated approaches to process and equipment quality assurance. Industrial engineers have developed various risk assessment tools that are used to identify and eliminate potential failures from a system or a process before a failure impacts a customer. These tools include, but are not limited to, process mapping, failure modes and effects analysis, fault tree analysis. Task Group 100 of the American Association of Physicists in Medicine has developed these tools and used them to formulate an example risk‐based quality management program for intensity‐modulated radiotherapy. This is a prospective risk assessment approach that analyzes potential error pathways inherent in a clinical process and then ranks them according to relative risk, typically before implementation, followed by the design of a new process or modification of the existing process. Appropriate controls are then put in place to ensure that failures are less likely to occur and, if they do, they will more likely be detected before they propagate through the process, compromising treatment outcome and causing harm to the patient. Such a prospective approach forms the basis of the work of Task Group 100 that has recently been approved by the AAPM. This session will be devoted to a discussion of these tools and practical examples of how these tools can be used in a given radiotherapy clinic to develop a risk based quality management program.Learning Objectives:

Learn how to design a process map for a radiotherapy process
Learn how to perform failure modes and effects analysis analysis for a given process
Learn what fault trees are all about
Learn how to design a quality management program based upon the information obtained from process mapping, failure modes and effects analysis and fault tree analysis.
Dunscombe: Director, TreatSafely, LLC and Center for the Assessment of Radiological Sciences; Consultant to IAEA and VarianThomadsen: President, Center for the Assessment of Radiological SciencesPalta: Vice President of the Center for the Assessment of Radiological Sciences
TU‐AB‐BRB‐01: Coverage Evaluation and Probabilistic Treatment Planning as a Margin Alternative
Authors: Siebers J. 
Published: June 2015

The accepted clinical method to accommodate targeting uncertainties inherent in fractionated external beam radiation therapy is to utilize GTV‐to‐CTV and CTV‐to‐PTV margins during the planning process to design a PTV‐conformal static dose distribution on the planning image set. Ideally, margins are selected to ensure a high (e.g. >95%) target coverage probability (CP) in spite of inherent inter‐ and intra‐fractional positional variations, tissue motions, and initial contouring uncertainties.Robust optimization techniques, also known as probabilistic treatment planning techniques, explicitly incorporate the dosimetric consequences of targeting uncertainties by including CP evaluation into the planning optimization process along with coverage‐based planning objectives. The treatment planner no longer needs to use PTV and/or PRV margins; instead robust optimization utilizes probability distributions of the underlying uncertainties in conjunction with CP‐evaluation for the underlying CTVs and OARs to design an optimal treated volume.This symposium will describe CP‐evaluation methods as well as various robust planning techniques including use of probability‐weighted dose distributions, probability‐weighted objective functions, and coverage optimized planning. Methods to compute and display the effect of uncertainties on dose distributions will be presented. The use of robust planning to accommodate inter‐fractional setup uncertainties, organ deformation, and contouring uncertainties will be examined as will its use to accommodate intra‐fractional organ motion. Clinical examples will be used to inter‐compare robust and margin‐based planning, highlighting advantages of robust‐plans in terms of target and normal tissue coverage. Robust‐planning limitations as uncertainties approach zero and as the number of treatment fractions becomes small will be presented, as well as the factors limiting clinical implementation of robust planning.Learning Objectives:

To understand robust‐planning as a clinical alternative to using margin‐based planning.
To understand conceptual differences between uncertainty and predictable motion.
To understand fundamental limitations of the PTV concept that probabilistic planning can overcome.
To understand the major contributing factors to target and normal tissue coverage probability.
To understand the similarities and differences of various robust planning techniques
To understand the benefits and limitations of robust planning techniques
TU‐CD‐BRB‐06: Deciphering Genomic Underpinnings of Quantitative MRI‐Based Radiomic Phenotypes of Invasive Breast Carcinoma
Authors: Zhu Y , Li H , Guo W , Drukker K , Yang S , Lan L , Giger M , Ji Y ,   for the TCIA Breast Cancer Group
Published: June 2015

Purpose:Magnetic Resonance Imaging(MRI) has been routinely used for diagnosis and assessment of breast cancer. Despite its wide applications in clinical practice, the relationship between the observed tumor MRI phenotypes and the genomic mechanism of tumorigenesis remains under‐explored, largely due to lack of data on both imaging and genomics for the same tumors.Methods:We combined data from The Cancer Genome Atlas(TCGA) and The Cancer Image Archive(TCIA), that included quantitatively extracted MRI phenotypes of 91 breast invasive carcinomas and their multi‐layer genomic data. Gene set enrichment analysis and regression analysis were performed to identify associations between tumor MRI radiomic phenotypes and various genomic and molecular subtypes of tumors. Patient groups defined by radiomic phenotypes and genomic platforms were also associated with tumor pathological stages and molecular receptor status using Fisher's exact test.Results:Significant associations (adjusted p‐values ≤ 0.1) were identified between radiomic phenotypes (characterizing tumor size, shape, margin, enhancement texture, and blood flow kinetics) and genomic features involved in multiple molecular regulation layers (including pathway gene expressions, pathway copy number variations, gene somatic mutations, miRNA expressions, and protein expressions). Transcriptional activities of various genetic pathways were dominantly positively associated with tumor size and blurred tumor margin. miRNA activity significantly associated with tumor size and enhancement textures, but not with phenotypes describing tumor shape, margin, and blood flow kinetics. Patient groups defined by radiomic phenotypes were associated with tumor T stage and overall stage (p‐values ≤ 0.072). Genomic platforms defined patient groups associated with the status of progesterone and estrogen receptors (p‐values ≤ 0.0000427) and pathological stages (p‐values ≤ 0.056).Conclusion:We present these findings as a resource shedding insight on the connection between underlying genetic mechanisms and observed tumor radiomic phenotypes, which forms a basis for future studies using non‐invasive MRI techniques for accurate cancer diagnosis and prognosis.
TU‐F‐CAMPUS‐I‐01: Statistical Iterative Reconstruction for Perfusion CT with a Prior‐Image Induced Hybrid Nonlocal Means Regularization
Authors: Li B , Lyu Q , Ma J , Wang J 
Published: June 2015

Purpose:In CT perfusion imaging, an initial phase CT acquired with a high‐dose protocol can be used to improve the image quality of later phase CT acquired with a low‐dose protocol. For dynamic regions, signals in the later low‐dose CT may not be completely recovered if the initial CT heavily regularizes the iterative reconstruction process. To overcome the limitation of the conventional prior image induced penalty, we propose a hybrid nonlocal means (NLM) regularization for iterative reconstruction of perfusion CT.Methods:The hybrid penalty is constructed by combining the NLM of initial high‐dose CT in the stationary region and later low‐dose CT in the dynamic region. The stationary and dynamic regions are determined by the similarity between the initial high‐dose scan and later low‐dose scan, where the similarity is defined as Gaussian distance between patch‐window of the same pixel of the two scans. The similarity measure is then used to weight the influence of the initial high‐dose CT. For regions with high similarity (e.g., stationary region), initial high‐dose CT will play a dominant role in regularizing the solution. For regions with low similarity (e.g., dynamic region), the regularization will rely on low‐dose scan itself. This new hybrid NLM (hNLM) penalty is then incorporated into the penalized weighted least‐squares (PWLS) for perfusion CT reconstruction. Digital and anthropomorphic phantom studies were performed to evaluate the PWLS‐hNLM algorithm.Results:Both phantom studies show that the PWLS‐hNLM algorithm is superior to the conventional penalty term without considering the signal changes within dynamic region. In the dynamic region, the reconstruction error measured by root mean square error is reduced by 50% in PWLS‐hNLM reconstructed image.Conclusion:The PWLS‐hNLM algorithm can effectively use initial high‐dose CT to reconstruct low‐dose perfusion CT in the stationary region while avoiding its influence in the dynamic region.
Hairpin Telomere Resolvases
Authors: Kobryn Kerri , Chaconas George 
Published: June 2015

ABSTRACT

Covalently closed hairpin ends, also known as hairpin telomeres, provide an unusual solution to the end replication problem. The hairpin telomeres are generated from replication intermediates by a process known as telomere resolution. This is a DNA breakage and reunion reaction promoted by hairpin telomere resolvases (also referred to as protelomerases) found in a limited number of phage and bacteria. The reaction promoted by these enzymes is a chemically isoenergetic two-step transesterification without a requirement for divalent metal ions or high-energy cofactors and uses an active site and mechanism similar to that for type IB topoisomerases and tyrosine recombinases. The small number of unrelated telomere resolvases characterized to date all contain a central, catalytic core domain with the active site, but in addition carry variable C- and N-terminal domains with different functions. Similarities and differences in the structure and function of the telomere resolvases are discussed. Of particular interest are the properties of the
Borrelia
telomere resolvases, which have been studied most extensively at the biochemical level and appear to play a role in shaping the unusual segmented genomes in these organisms and, perhaps, to play a role in recombinational events.
Retroviral Integrase Structure and DNA Recombination Mechanism
Authors: Engelman Alan , Cherepanov Peter 
Published: June 2015

ABSTRACT
Due to the importance of human immunodeficiency virus type 1 (HIV-1) integrase as a drug target, the biochemistry and structural aspects of retroviral DNA integration have been the focus of intensive research during the past three decades. The retroviral integrase enzyme acts on the linear double-stranded viral DNA product of reverse transcription. Integrase cleaves specific phosphodiester bonds near the viral DNA ends during the 3′ processing reaction. The enzyme then uses the resulting viral DNA 3′-OH groups during strand transfer to cut chromosomal target DNA, which simultaneously joins both viral DNA ends to target DNA 5′-phosphates. Both reactions proceed via direct transesterification of scissile phosphodiester bonds by attacking nucleophiles: a water molecule for 3′ processing, and the viral DNA 3′-OH for strand transfer. X-ray crystal structures of prototype foamy virus integrase-DNA complexes revealed the architectures of the key nucleoprotein complexes that form sequentially during the integration process and explained the roles of active site metal ions in catalysis. X-ray crystallography furthermore elucidated the mechanism of action of HIV-1 integrase strand transfer inhibitors, which are currently used to treat AIDS patients, and provided valuable insights into the mechanisms of viral drug resistance.
Host Factors in Retroviral Integration and the Selection of Integration Target Sites
Authors: Craigie Robert , Bushman Frederic D. 
Published: June 2015

ABSTRACTIn order to replicate, a retrovirus must integrate a DNA copy of the viral RNA genome into a chromosome of the host cell. The study of retroviral integration has advanced considerably in the past few years. Here we focus on host factor interactions and the linked area of integration targeting. Genome-wide screens for cellular factors affecting HIV replication have identified a series of host cell proteins that may mediate subcellular trafficking for preintegration complexes, nuclear import, and integration target site selection. The cell transcriptional co-activator protein LEDGF/p75 has been identified as a tethering factor important for HIV integration, and recently, BET proteins (Brd2, 4, and 4) have been identified as tethering factors for the gammaretroviruses. A new class of HIV inhibitors has been developed targeting the HIV-1 IN-LEDGF binding site, though surprisingly these inhibitors appear to block assembly late during replication and do not act at the integration step. Going forward, genome-wide studies of HIV–host interactions offer many new starting points to investigate HIV replication and identify potential new inhibitor targets.
vlsAntigenic Variation Systems of Lyme DiseaseBorrelia: Eluding Host Immunity through both Random, Segmental Gene Conversion and Framework Heterogeneity
Authors: Norris Steven J. 
Published: June 2015

ABSTRACTSpirochetes that cause Lyme borreliosis (also called Lyme disease) possess thevlslocus, encoding an elaborate antigenic variation system. This locus contains the expression sitevlsEas well as a contiguous array ofvlssilent cassettes, which contain variations of the central cassette region ofvlsE. The locus is present on one of the many linear plasmids in the organism, e.g. plasmid lp28-1 in the strainBorrelia burgdorferiB31. Changes in the sequence ofvlsEoccur continuously during mammalian infection and consist of random, segmental, unidirectional recombination events between the silent cassettes and the cassette region ofvlsE. These gene conversion events do not occur duringin vitroculture or the tick portion of the infection cycle ofB. burgdorferior the other relatedBorreliaspecies that cause Lyme disease. The mechanism of recombination is largely unknown, but requires the RuvAB Holliday junction branch migrase. Other features of thevlslocus also appear to be required, includingcislocations ofvlsEand the silent cassettes and high G+C content and GC skew. Thevlssystem is required for long-term survival of LymeBorreliain infected mammals and represents an important mechanism of immune evasion. In addition to sequence variation, immune selection also results in significant heterogeneity in the sequence of the surface lipoprotein VlsE. Despite antigenic variation, VlsE generates a robust antibody response, and both full-length VlsE and the C6 peptide (corresponding to invariant region 6) are widely used in immunodiagnostic tests for Lyme disease.
V(D)J Recombination: Mechanism, Errors, and Fidelity
Authors: Roth David B. 
Published: June 2015

ABSTRACT
V(D)J recombination, the mechanism responsible for generating antigen receptor diversity, has the potential to generate aberrant DNA rearrangements in developing lymphocytes. Indeed, the recombinase has been implicated in several different kinds of errors leading to oncogenic transformation. Here we review the basic aspects of V(D)J recombination, mechanisms underlying aberrant DNA rearrangements, and the types of aberrant events uncovered in recent genomewide analyses of lymphoid neoplasms.
Xer Site-Specific Recombination: Promoting Vertical and Horizontal Transmission of Genetic Information
Authors: Midonet Caroline , Barre Francois-Xavier 
Published: June 2015

ABSTRACT

Two related tyrosine recombinases, XerC and XerD, are encoded in the genome of most bacteria where they serve to resolve dimers of circular chromosomes by the addition of a crossover at a specific site,
dif
. From a structural and biochemical point of view they belong to the Cre resolvase family of tyrosine recombinases. Correspondingly, they are exploited for the resolution of multimers of numerous plasmids. In addition, they are exploited by mobile DNA elements to integrate into the genome of their host. Exploitation of Xer is likely to be advantageous to mobile elements because the conservation of the Xer recombinases and of the sequence of their chromosomal target should permit a quite easy extension of their host range. However, it requires means to overcome the cellular mechanisms that normally restrict recombination to
dif
sites harbored by a chromosome dimer and, in the case of integrative mobile elements, to convert dedicated tyrosine resolvases into integrases.
Phage-encoded Serine Integrases and Other Large Serine Recombinases
Authors: Smith Margaret C. M. 
Published: June 2015

ABSTRACT

The large serine recombinases (LSRs) are a family of enzymes, encoded in temperate phage genomes or on mobile elements, that precisely cut and recombine DNA in a highly controllable and predictable way. In phage integration, the LSRs act at specific sites, the
attP
site in the phage and the
attB
site in the host chromosome, where cleavage and strand exchange leads to the integrated prophage flanked by the recombinant sites
attL
and
attR
. The prophage can excise by recombination between
attL
and
attR
but this requires a phage-encoded accessory protein, the recombination directionality factor (RDF). Although the LSRs can bind specifically to all the recombination sites, only specific integrase-bound sites can pair in a synaptic complex prior to strand exchange. Recent structural information has led to a breakthrough in our understanding of the mechanism of the LSRs, notably how the LSRs bind to their substrates and how LSRs display this site-selectivity. We also understand that the RDFs exercise control over the LSRs by protein–protein interactions. Other recent work with the LSRs have contributed to our understanding of how all serine recombinases undergo strand exchange subunit rotation, facilitated by surfaces that resemble a molecular bearing.