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

Topoclimate effect on treeline elevation depends on the regional framework: A contrast between Southern Alps (New Zealand) and Apennines (Italy) forests

Deciphering the spatial patterns of alpine treelines is critical for understanding the ecosystem processes involved in the persistence of tree species and their altitudinal limit. Treelines are thought to be controlled by temperature, and other environmental variables but they have rarely been investigated in regions with different land-use change legacies. Here, we systematically investigated treeline elevation in the Apennines (Italy) and Southern Alps (New Zealand) with contrasting human history but similar biogeographic trajectories, intending to identify distinct drivers that affect their current elevation and highlight their respective peculiarities. Over 3622 km of Apennines, treeline elevation was assessed in 302 mountain peaks and in 294 peaks along 4504 km of Southern Alps. The major difference between the Southern Alps and Apennines treeline limit is associated with their mountain aspects. In the Southern Alps, the scarcely anthropized Nothofagus treeline elevation was higher on the warmer equator-facing slopes than on the pole-facing ones. Contrary to what would be expected based on temperature limitation, the elevation of Fagus sylvatica treelines in the Apennines was higher on colder, pole-facing slopes than on human-shaped equator-facing, warmer mountainsides. Pervasive positive correlations were found between treeline elevation and temperature in the Southern Alps but not in the Apennines. While the position of the Fagus and Nothofagus treelines converge on similar isotherms of annual average temperature, a striking isothermal difference between the temperatures of the hottest month on which the two taxonomic groups grow exists. We conclude that actual treeline elevation reflects the ecological processes driven by a combination of local-scale topoclimatic conditions, and human disturbance legacy. Predicting dynamic processes affecting current and future alpine treeline position requires further insight into the modulating influences that are currently understood at a regional scale

Mismatch Repair Proteins Initiate Epigenetic Alterations during Inflammation-Driven Tumorigenesis

Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model of inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment of epigenetic proteins to chromatin, initiating methylation and gene silencing in tumors. Compared with normal epithelium and noninflammation-induced tumors, inflammation-induced tumors gained DNA methylation at CpG islands, some of which are associated with putative tumor suppressor genes. Hypermethylated genes exhibited enrichment of repressive chromatin marks and reduced expression prior to tumorigenesis, at a time point coinciding with peak levels of inflammation-associated DNA damage. Loss of MutS homolog 2 (MSH2), a mismatch repair (MMR) protein, abrogated early inflammation-induced epigenetic alterations and DNA hypermethylation alterations observed in inflammation-induced tumors. These results indicate that early epigenetic alterations initiated by inflammation and MMR proteins lead to gene silencing during tumorigenesis, revealing a novel mechanism of epigenetic alterations in inflammation-driven cancer. Understanding such mechanisms will inform development of pharmacotherapies to reduce carcinogenesis

Reduction of Murine Colon Tumorigenesis Driven by Enterotoxigenic Bacteroides fragilis Using Cefoxitin Treatment

BACKGROUND: Chronic inflammation and composition of the colon microbiota have been associated with colorectal cancer in humans. The human commensal enterotoxigenic Bacteroides fragilis (ETBF) is linked to both inflammatory bowel disease and colorectal cancer and, in our murine model, causes interleukin 17A (IL-17A)-dependent colon tumors. In these studies, we hypothesized that persistent colonization by ETBF is required for tumorigenesis. METHODS: We established a method for clearing ETBF in mice, using the antibiotic cefoxitin. Multiple intestinal neoplasia mice were colonized with ETBF for the experiment duration or were cleared of infection after 5 or 14 days. Gross tumors and/or microadenomas were then evaluated. In parallel, IL-17A expression was evaluated in wild-type littermates. RESULTS: Cefoxitin treatment resulted in complete and durable clearance of ETBF colonization. We observed a stepwise increase in median colon tumor numbers as the duration of ETBF colonization increased before cefoxitin treatment. ETBF eradication also significantly decreased mucosal IL-17A expression. CONCLUSIONS: The timing of ETBF clearance profoundly influences colon adenoma formation, defining a period during which the colon is susceptible to IL-17A-dependent tumorigenesis in this murine model. This model system can be used to study the microbiota-dependent and molecular mechanisms contributing to IL-17A-dependent colon tumor initiation

Regression, developmental trajectory and associated problems in disorders in the autism spectrum: the SNAP study

We report rates of regression and associated findings in a population derived group of 255 children aged 9-14 years, participating in a prevalence study of autism spectrum disorders (ASD); 53 with narrowly defined autism, 105 with broader ASD and 97 with non-ASD neurodevelopmental problems, drawn from those with special educational needs within a population of 56,946 children. Language regression was reported in 30% with narrowly defined autism, 8% with broader ASD and less than 3% with developmental problems without ASD. A smaller group of children were identified who underwent a less clear setback. Regression was associated with higher rates of autistic symptoms and a deviation in developmental trajectory. Regression was not associated with epilepsy or gastrointestinal problems

Interactivity Mitigates the Impact of Working Memory Depletion on Mental Arithmetic Performance

Doing long sums in the absence of complementary actions or artefacts is a multi-step procedure that quickly taxes working memory; congesting the phonological loop further handicaps performance. In the experiment reported here, participants completed long sums either with hands down?the low interactivity condition?or by moving numbered tokens?the high interactivity condition?while they repeated ?the? continuously, loading the phonological loop, or not. As expected, interactivity and articulatory suppression substantially affected performance; critically, the effect of articulatory suppression was stronger in the low than in the high interactivity condition. In addition, independent measure of mathematics anxiety predicted the impact of articulatory suppression on performance only in the low (not high) interactivity condition. These findings suggest that interactivity augmented overall or systemic working memory resources and diminished the effect of mathematics anxiety, underscoring the importance of characterizing the properties of the system as it is configured by the dynamic agent-environment coupling

Key Variants via the Alzheimer\u27s Disease Sequencing Project Whole Genome Sequence Data

INTRODUCTION: Genome-wide association studies (GWAS) have identified loci associated with Alzheimer\u27s disease (AD) but did not identify specific causal genes or variants within those loci. Analysis of whole genome sequence (WGS) data, which interrogates the entire genome and captures rare variations, may identify causal variants within GWAS loci. METHODS: We performed single common variant association analysis and rare variant aggregate analyses in the pooled population (N cases = 2184, N controls = 2383) and targeted analyses in subpopulations using WGS data from the Alzheimer\u27s Disease Sequencing Project (ADSP). The analyses were restricted to variants within 100 kb of 83 previously identified GWAS lead variants. RESULTS: Seventeen variants were significantly associated with AD within five genomic regions implicating the genes OARD1/NFYA/TREML1, JAZF1, FERMT2, and SLC24A4. KAT8 was implicated by both single variant and rare variant aggregate analyses. DISCUSSION: This study demonstrates the utility of leveraging WGS to gain insights into AD loci identified via GWAS