Verification of TG-61 dose for synchrotron-produced monochromatic x-ray beams using fluence-normalized MCNP5 calculations

Ion chamber dosimetry is being used to calibrate dose for cell irradiations designed to investigate photoactivated Auger electron therapy at the Louisiana State University CAMD synchrotron facility. This study performed a dosimetry intercomparison for synchrotron-produced monochromatic x-ray beams at 25 and 35 keV. Ion chamber depth-dose measurements in a PMMA phantom were compared with the product of MCNP5 Monte Carlo calculations of dose per fluence and measured incident fluence. Monochromatic beams of 25 and 35 keV were generated on the tomography beamline at CAMD. A cylindrical, air-equivalent ion chamber was used to measure the ionization created in a 10x10x10-cm3 PMMA phantom for depths from 0.6 to 7.7 cm. The American Association of Physicists in Medicine TG-61 protocol was applied to convert measured ionization into dose. Photon fluence was determined using a NaI detector to make scattering measurements of the beam from a thin polyethylene target at angles 30 degrees to 60 degrees. Differential Compton and Rayleigh scattering cross sections obtained from xraylib, an ANSI C library for x-ray-matter interactions, were applied to derive the incident fluence. MCNP5 simulations of the irradiation geometry provided the dose deposition per photon fluence as a function of depth in the phantom. At 25 keV the fluence-normalized MCNP5 dose overestimated the ion-chamber measured dose by an average of 7.2+/-3.0% to 2.1+/-3.0% for PMMA depths from 0.6 to 7.7 cm, respectively. At 35 keV the fluence-normalized MCNP5 dose underestimated the ion-chamber measured dose by an average of 1.0+/-3.4% to 2.5+/-3.4%, respectively. These results showed that TG-61 ion chamber dosimetry, used to calibrate dose output for cell irradiations, agreed with fluence-normalized MCNP5 calculations to within approximately 7% and 3% at 25 and 35 keV, respectively.Comment: 22 pages, 5 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS)

We present an efficient pipeline enabling high-throughput analysis of protein structure in solution with small angle X-ray scattering (SAXS). Our SAXS pipeline combines automated sample handling of microliter volumes, temperature and anaerobic control, rapid data collection and data analysis, and couples structural analysis with automated archiving. We subjected 50 representative proteins, mostly from Pyrococcus furiosus, to this pipeline and found that 30 were multimeric structures in solution. SAXS analysis allowed us to distinguish aggregated and unfolded proteins, define global structural parameters and oligomeric states for most samples, identify shapes and similar structures for 25 unknown structures, and determine envelopes for 41 proteins. We believe that high-throughput SAXS is an enabling technology that may change the way that structural genomics research is done

The biopax community standard for pathway data sharing

BioPAX (Biological Pathway Exchange) is a standard language to represent biological pathways at the molecular and cellular level. Its major use is to facilitate the exchange of pathway data (http://www.biopax.org). Pathway data captures our understanding of biological processes, but its rapid growth necessitates development of databases and computational tools to aid interpretation. However, the current fragmentation of pathway information across many databases with incompatible formats presents barriers to its effective use. BioPAX solves this problem by making pathway data substantially easier to collect, index, interpret and share. BioPAX can represent metabolic and signaling pathways, molecular and genetic interactions and gene regulation networks. BioPAX was created through a community process. Through BioPAX, millions of interactions organized into thousands of pathways across many organisms, from a growing number of sources, are available. Thus, large amounts of pathway data are available in a computable form to support visualization, analysis and biological discovery

Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-ɛ4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ɛ4 being the major genetic risk factor for AD