Development of an X-band Photoinjector at SLAC

As part of a National Cancer Institute contract to develop a compact source of monoenergetic X-rays via Compton backscattering, we have completed the design and construction of a 5.5 cell Photoinjector operating at 11.424 GHz. Successful completion of this project will result in the capability of generating a monoenergetic X-ray beam, continuously tunable from 20 - 85 KeV. The immediate goal is the development of a Photoinjector producing 7 MeV, 0.5 nC, sub-picosecond electron bunches with normalized RMS emittances of approximately 1 pi-mm-mR at repetition rates up to 60 Hz. This beam will then be further accelerated to 60 MeV using a 1.05 m accelerating structure. This Photoinjector is somewhat different than the traditional 1.5 cell design both because of the number of cells and the symmetrically fed input coupler cell. Its operating frequency is also unique. Since the cathode is non-removable, cold-test tuning was somewhat more difficult than in other designs. We will present results of "bead-drop" measurements used in tuning this structure. Initial beam measurements are currently in progress and results will be presented as well as results of RF conditioning to high gradients at X-band. Details of the RF system, emittance-compensating solenoid, and cathode laser system as well as PARMELA simulations will also be presented.Comment: 3 pages, 6 figures, 1 Table, LINAC 200

Extraction efficiency of drifting electrons in a two-phase xenon time projection chamber

We present a measurement of the extraction efficiency of quasi-free electrons from the liquid into the gas phase in a two-phase xenon time-projection chamber. The measurements span a range of electric fields from 2.4 to 7.1 kV/cm in the liquid xenon, corresponding to 4.5 to 13.1 kV/cm in the gaseous xenon. Extraction efficiency continues to increase at the highest extraction fields, implying that additional charge signal may be attained in two-phase xenon detectors through careful high-voltage engineering of the gate-anode region

Calibration of a two-phase xenon time projection chamber with a 37^{37}Ar source

We calibrate a two-phase xenon detector at 0.27 keV in the charge channel and at 2.8 keV in both the light and charge channels using a $^{37}$Ar source that is directly released into the detector. We map the light and charge yields as a function of electric drift field. For the 2.8 keV peak, we calculate the Thomas-Imel box parameter for recombination and determine its dependence on drift field. For the same peak, we achieve an energy resolution, $E_{\sigma}/E_{mean}$, between 9.8% and 10.8% for 0.1 kV/cm to 2 kV/cm electric drift fields.Comment: 12 pages, 7 figure

Genetic Correlates of Brain Aging on MRI and Cognitive Test Measures: A Genome-Wide Association and Linkage Analysis in the Framingham Study

BACKGROUND: Brain magnetic resonance imaging (MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease (AD). We conducted a genome-wide association (GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. METHODS: A total of 705 stroke- and dementia-free Framingham participants (age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing (1999–2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations (GEE) and family based association tests (FBAT) in additive models to relate qualifying single nucleotide polymorphisms (SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency ≥ 0.10, genotypic call rate ≥ 0.80, and Hardy-Weinberg equilibrium p-value ≥ 0.001) to multivariable-adjusted residuals of 9 MRI measures including total cerebral brain (TCBV), lobar, ventricular and white matter hyperintensity (WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. RESULTS: The strongest gene-phenotype association in FBAT analyses was between SORL1 (rs1131497; p = 3.2 × 10-6) and abstract reasoning, and in GEE analyses between CDH4 (rs1970546; p = 3.7 × 10-8) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations (25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously reported linkage of WMH on chromosome 4 and describe linkage of reading performance to a marker on chromosome 18 (GATA11A06), previously linked to dyslexia (LOD scores = 2.2 and 5.1). CONCLUSION: Our results suggest that genes associated with clinical neurological disease also have detectable effects on subclinical phenotypes. These hypothesis generating data illustrate the use of an unbiased approach to discover novel pathways that may be involved in brain aging, and could be used to replicate observations made in other studies.National Institutes of Health National Center for Research Resources Shared Instrumentation grant (ISI0RR163736-01A1); National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institute of Aging (5R01-AG08122, 5R01-AG16495); National Institute of Neurological Disorders and Stroke (5R01-NS17950

Autophagy gene haploinsufficiency drives chromosome instability, increases migration, and promotes early ovarian tumors.

Autophagy, particularly with BECN1, has paradoxically been highlighted as tumor promoting in Ras-driven cancers, but potentially tumor suppressing in breast and ovarian cancers. However, studying the specific role of BECN1 at the genetic level is complicated due to its genomic proximity to BRCA1 on both human (chromosome 17) and murine (chromosome 11) genomes. In human breast and ovarian cancers, the monoallelic deletion of these genes is often co-occurring. To investigate the potential tumor suppressor roles of two of the most commonly deleted autophagy genes in ovarian cancer, BECN1 and MAP1LC3B were knocked-down in atypical (BECN1+/+ and MAP1LC3B+/+) ovarian cancer cells. Ultra-performance liquid chromatography mass-spectrometry metabolomics revealed reduced levels of acetyl-CoA which corresponded with elevated levels of glycerophospholipids and sphingolipids. Migration rates of ovarian cancer cells were increased upon autophagy gene knockdown. Genomic instability was increased, resulting in copy-number alteration patterns which mimicked high grade serous ovarian cancer. We further investigated the causal role of Becn1 haploinsufficiency for oncogenesis in a MISIIR SV40 large T antigen driven spontaneous ovarian cancer mouse model. Tumors were evident earlier among the Becn1+/- mice, and this correlated with an increase in copy-number alterations per chromosome in the Becn1+/- tumors. The results support monoallelic loss of BECN1 as permissive for tumor initiation and potentiating for genomic instability in ovarian cancer

Optimization of Supercritical Carbon Dioxide Extraction of Rice Bran Oil and γ-Oryzanol Using Multi-Factorial Design of Experiment

After rice harvesting, the milling processes generate many by-products including husk, bran, germs, and broken rice representing around 40% of the total grain. Bran, one of the external cereal layers, contains proteins, dietary fibers, minerals, and lipids. One of the most common rice bran utilization is the extraction of rice bran oil (RBO). Among all vegetable oils, RBO presents a unique chemical composition rich in antioxidant compounds such as γ-oryzanol that provide several beneficial properties. RBO is generally extracted by exploiting hexane, a solvent toxic to the environment and human health. The growing demand for this oil has led researchers to look for more sustainable extraction techniques. Supercritical carbon dioxide (SC-CO2) has been successfully applied to extract oil and functional compounds from several matrices. In this work, the SC-CO2 extraction of RBO was optimized using a Design of Experiment (DoE) on a pilot scale. "The DoE approach involving multilinear regression allowed modelling the yield in RBO and gamma oryzanol as a function of temperature and pressure, keeping the extraction time constant, as decided by the company. This approach made it possible to optimize the extraction yield and to identify the best temperature (40 °C), while also highlighting that pressure did not play any influential role in the process, at least concerning the analyzed experimental domain on this industrial plant. A model for computing the extraction yield as a function of temperature and pressure was obtained. This study shows that it is possible to obtain good quality RBO, rich in γ-oryzanol and essential fatty acids, using low temperatures and pressures, starting from a rice milling by-product. Graphical Abstract: [Figure not available: see fulltext.

Genetic analyses of longitudinal phenotype data: a comparison of univariate methods and a multivariate approach

BACKGROUND: We explored three approaches to heritability and linkage analyses of longitudinal total cholesterol levels (CHOL) in the Genetic Analysis Workshop 13 simulated data without knowing the answers. The first two were univariate approaches and used 1) baseline measure at exam one or 2) summary measures such as mean and slope from multiple exams. The third method was a multivariate approach that directly models multiple measurements on a subject. A variance components model (SOLAR) was employed in the univariate approaches. A mixed regression model with polynomials was employed in the multivariate approach and implemented in SAS/IML. RESULTS: Using the baseline measure at exam 1, we detected all baseline or slope genes contributing a substantial amount (0.08) of variance (LOD > 3). Compared to the baseline measure, the mean measures yielded slightly higher LOD at the slope genes, and a lower LOD at the baseline genes. The slope measure produced a somewhat lower LOD for the slope gene than did the mean measure. Descriptive information on the pattern of changes in gene effects with age was estimated for three linked loci by the third approach. CONCLUSION: We found simple univariate methods may be effective to detect genes affecting longitudinal phenotypes but may not fully reveal temporal trends in gene effects. The relative efficiency of the univariate methods to detect genes depends heavily on the underlying model. Compared with the univariate approaches, the multivariate approach provided more information on temporal trends in gene effects at the cost of more complicated modelling and more intense computations

Fluorescent Detection of Bromoperoxidase Activity in Microalgae and Planktonic Microbial Communities Using Aminophenyl Fluorescein

Among planktonic communities haloperoxidase enzymes may play a role in the control of intracellular and extracellular reactive oxygen species, in the generation of halogenated organic compounds and in chemical interactions between microbes. We introduce a sensitive fluorometric assay with a large dynamic range that is based on the dearylation of aminophenyl fluorescein (APF) to fluorescein by highly reactive oxygen species. Bromoperoxidase and chloroperoxidase enzymes catalyze the reaction between hydrogen peroxide and halides to generate highly reactive hypohalite intermediates able to dearylate APF. The fundamentals and standardization of the approach are illustrated using a partially purified, vanadium-dependent bromoperoxidase from the red seaweed Corallina officinalis. Laboratory cultures of two polar diatoms, Porosira glacialis and Fragilariopsis cylindrus, are used to illustrate the sensitivity and potential applications of the approach for in vitro, in vivo and in situ measurements of bromoperoxidase activity. These two diatoms differ in biovolume-specific bromoperoxidase activity by 2-orders of magnitude, from 5.4 to 0.044 fmol fluorescein μm-3 h-1, respectively. The approach is also used to investigate the partition of haloperoxidase activity between different size fractions of summer coastal planktonic communities, illustrating that generally more than 50% of the haloperoxidase activity occurred in a &gt;10 μm size fraction that was dominated by diatoms. The assay has the potential to be of value in many aspects of haloperoxidase research, including developing an improved understanding of the roles of haloperoxidase enzymes in microbial planktonic communities

Systems of education governance and cultures of justice in Ireland, Scotland and Pakistan

This chapter compares the issue of cultures of justice in the systems of education governance in three education systems: Ireland, Scotland and Pakistan. The focus for the comparison are the current policies which shape the regulation of education. These policies were reviewed to identify key issues relating to social justice and equality, decision-making and accountability. From the analysis of each system, three central issues were identified: firstly, the improvement of a state education system; secondly, the degree of decentralisation and centralisation in governance structures and thirdly, the expectations placed on school leaders. The chapter concludes by discussing the tensions between the drive for system improvement and opportunities for school leaders to build strategies to address issues of inequality in schools