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

Real-time software methodologies: Are they suitable for developing Manufacturing control software?

Computer-Integrated Manufacturing (CIM) systems may be classified as real-time systems. Hence, the applicability of methodologies that are developed for specifying, designing, implementing, testing, and evolving real-time software is investigated in this article.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45553/1/10696_2005_Article_BF01358949.pd

Microstructural influence of the thermal behavior of arc deposited TiAlN coatings with high aluminum content

The influence of the microstructure on the thermal behavior of cathodic arc deposited TiAlN coatings was studied as a function of isothermal annealing. Two compositionally similar but structurally different coatings were compared, a Ti0\ub734Al0\ub766N0.96 coating with a fine-grain structure consisting of a mixture of cubic (c) and hexagonal (h) phases, and a Ti0\ub740Al0\ub760N0.94 coating with a coarse-grain structure of cubic phase. By in situ wide-angle synchrotron x-ray scattering, spinodal decomposition was confirmed in both coatings. The increased amount of internal interfaces lowered the decomposition temperature by 50 \ub0C for the dual-phase coating. During the subsequent isothermal anneal at 1000 \ub0C, a transformation from c-AlN to h-AlN took place in both coatings. After 50 min of isothermal annealing, atom probe tomography detected small amounts of Al (∼2 at.%) in the c-TiN rich domains and small amounts of Ti (∼1 at.%) in the h-AlN rich domains of the coarse-grained single-phase Ti0\ub740Al0\ub760N0.94 coating. Similarly, at the same conditions, the fine-grained dual-phase Ti0\ub734Al0\ub766N0.96 coating exhibits a higher Al content (∼5 at.%) in the c-TiN rich domains and higher Ti content (∼15 at.%) in the h-AlN rich domains. The study shows that the thermal stability of TiAlN is affected by the microstructure and that it can be used to tune the reaction pathway of decomposition favorably

Patient Profiles and Health Status Outcomes for Peripheral Artery Disease in High-Income Countries:A Comparison Between the United States and the Netherlands

OBJECTIVES: Peripheral artery disease (PAD) is a global disease. Understanding variability in patient profiles and PAD-specific health status outcomes across health system countries can provide insights into improving PAD care. We compared these features between 2 high-income countries, the United States (US) and the Netherlands. MATERIALS AND METHODS: Patients were identified from the Patient-centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories (PORTRAIT) study - a prospective, international registry of patients presenting to vascular specialty clinics for new onset, or exacerbation of PAD symptoms. PAD-specific health status was measured with the Peripheral Artery Questionnaire (PAQ). General linear mixed models for repeated measures were used to study baseline, 3-, 6-, and 12-month PAD-specific health status outcomes (PAQ summary score) between US and the Netherlands. RESULTS: Out of a total of 1,114 patients, 748 patients (67.1%) were from the US and 366 (32.9%) from the Netherlands. US patients with PAD were older, with more financial barriers, higher cardiovascular risk factor burden, and lower referral rates for exercise treatment (p < 0.001). They had significantly worse PAD-specific adjusted health status scores at presentation, 3-, 6- and 12 months of follow-up (all p < 0.0001). Magnitude of change in 1-year health status scores was smaller in the US cohort as compared with the Netherlands. CONCLUSION: Compared with the Dutch cohort, US patients had worse adjusted PAD-specific health status scores at all time point, improving less over time, despite treatment. Leveraging inter-country differences in care and outcomes could provide important insights into optimizing PAD outcomes

Developing control and integration software for flexible manufacturing systems

The slow growth of computer-integrated manufacturing is attributed to the complexity of designing and implementing their control and integration software. This article expands on a methodology for designing and implementing this software that was introduced in [16]. The goal of this methodology is to build flexible and resuable control and integration software for computer-integrated manufacturing systems. It hinges upon the concepts of software/hardware components, their assemblages, a distributed common language environment, formal models, and generic controllers. Major sources of flexibility are obtained by decoupling process plan models from the model of the factory floor and by using a generic controller. Reusability is achieved by building selfcontained software/hardware components with general, possibly parametrized, interfaces. The interplay between simulated and actual hardware internals of software/hardware components is used as the basis of a testing strategy that performs off-line simulation followed by on-line testing.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43095/1/10952_2005_Article_BF02265064.pd

FAK/src-Family Dependent Activation of the Ste20-Like Kinase SLK Is Required for Microtubule-Dependent Focal Adhesion Turnover and Cell Migration

Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal

“Tem Química na cozinha?” – Elaboração e aplicação de uma Oficina Temática para divulgação científica

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A computational approach to identify point mutations associated with occult hepatitis B: significant mutations affect coding regions but not regulative elements of HBV

<p>Abstract</p> <p>Background</p> <p>Occult Hepatitis B Infection (OBI) is characterized by absence of serum HBsAg and persistence of HBV-DNA in liver tissue, with low to undetectable serum HBV-DNA. The mechanisms underlying OBI remain to be clarified. To evaluate if specific point mutations of HBV genome may be associated with OBI, we applied an approach based on bioinformatics analysis of complete genome HBV sequences. In addition, the feasibility of bioinformatics prediction models to classify HBV infections into OBI and non-OBI by molecular data was evaluated.</p> <p>Methods</p> <p>41 OBI and 162 non-OBI complete genome sequences were retrieved from GenBank, aligned and subjected to univariable analysis including statistical evaluation. Their S coding region was analyzed for Stop codon mutations too, while S amino acid variability could be evaluated for genotype D only, due to the too small number of available complete genome OBI sequences from other genotypes.</p> <p>Prediction models were derived by multivariable analysis using Logistic Regression, Rule Induction and Random Forest approaches, with extra-sample error estimation by Multiple ten-fold Cross-Validation (MCV). Models were compared by t-test on the Area Under the Receiver Operating Characteristic curve (AUC) distributions obtained from the MCV runs for each model against the best-performing model.</p> <p>Results</p> <p>Variations in seven nucleotide positions were significantly associated with OBI, and occurred in 11 out of 41 OBI sequences (26.8%): likely, other mutations did not reach statistical significance due to the small size of OBI dataset. All variations affected at least one HBV coding region, but none of them mapped to regulative elements. All viral proteins, with the only exception of the X, were affected. Stop codons in the S, that might account for absence of serum HBsAg, were not significantly enriched in OBI sequences. In genotype D, amino acid variability in the S was higher in OBI than non-OBI, particularly in the immunodominant region. A Random Forest prediction model showed the best performance, but all models were not satisfactory in terms of specificity, due to the small sample size of OBIs; however results are promising in the perspective of a broader dataset of complete genome OBI sequences.</p> <p>Conclusions</p> <p>Data suggest that point mutations rarely occur in regulative elements of HBV, if ever, and contribute to OBI by affecting different viral proteins, suggesting heterogeneous mechanisms may be responsible for OBI, including, at least in genotype D, an escape mutation mechanism due to imperfect immune control. It appears possible to derive prediction models based on molecular data when a larger set of complete genome OBI sequences will become available.</p

A Genome-Wide Association Study of Total Bilirubin and Cholelithiasis Risk in Sickle Cell Anemia

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10−8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10−25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10−4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities