2006 A Spotlight on San Diego\u27s Third Sector

In conjunction with the University of San Francisco\u27s Institute for Nonprofit Organization Management, the Center produced a report focused on the contributions of the San Diego nonprofit sector to the local economy. This report\u27s intent is to create an understanding of the nonprofit sector, measure its capacity & economic contributions, and chart its future. This project was presented November 13, 2006.https://digital.sandiego.edu/npi-stateofnp/1011/thumbnail.jp

A Spotlight on San Diego's Third Sector

In conjunction with the University of San Francisco's Institute for Nonprofit Organization Management, the Center produced a report focused on the contributions of the San Diego nonprofit sector to the local economy. This report's intent is to create an understanding of the nonprofit sector, measure its capacity and economic contributions, and chart its future. This project was presented November 13, 2006

Event detection using roles and relationships of entities

A method, system, and computer program product for event detection using roles and relationships of entities are provided in the illustrative embodiments. A training event and a set of entities participating in the training event are identified in a training data. For a first entity in the set of entities, a first role occupied by the entity in the event is determined. A behavior attribute is assigned to the first role. A relationship of the first role with a second role corresponding to a second entity in the set of entities is determined. An event rule is constructed to detect an event corresponding to the training event in new data and comprising a plurality of roles, behavior attributes, and the relationship. The plurality of roles includes the first role and the second role, and the plurality of behavior attributes includes the behavior attribute assigned to the first role.Board of Regents, University of Texas Syste

Cancer-Associated Fibroblasts Neutralize the Anti-tumor Effect of CSF1 Receptor Blockade by Inducing PMN-MDSC Infiltration of Tumors.

Tumor-associated macrophages (TAM) contribute to all aspects of tumor progression. Use of CSF1R inhibitors to target TAM is therapeutically appealing, but has had very limited anti-tumor effects. Here, we have identified the mechanism that limited the effect of CSF1R targeted therapy. We demonstrated that carcinoma-associated fibroblasts (CAF) are major sources of chemokines that recruit granulocytes to tumors. CSF1 produced by tumor cells caused HDAC2-mediated downregulation of granulocyte-specific chemokine expression in CAF, which limited migration of these cells to tumors. Treatment with CSF1R inhibitors disrupted this crosstalk and triggered a profound increase in granulocyte recruitment to tumors. Combining CSF1R inhibitor with a CXCR2 antagonist blocked granulocyte infiltration of tumors and showed strong anti-tumor effects

Recruitment and follow-up of adolescent and young adult cancer survivors: the AYA HOPE Study

IntroductionCancer is rare in adolescents and young adults (AYA), but these patients have seen little improvement in survival in contrast to most other age groups. Furthermore, participation in research by AYAs is typically low. We conducted a study to examine the feasibility of recruiting a population-based sample of AYA survivors to examine issues of treatment and health outcomes.MethodsIndividuals diagnosed in 2007-08 and age 15-39 at the time of diagnosis with acute lymphocytic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, germ cell cancer or sarcoma were identified by 7 Surveillance, Epidemiology, and End-Results (SEER) cancer registries, mailed surveys within 14 months after diagnosis and again a year later, and had medical records reviewed.Results525 (43%) of the eligible patients responded, 39% refused and 17% were lost to follow-up. Extensive efforts were required for most potential respondents (87%). 76% of respondents completed the paper rather than online survey version. In a multivariate model, age, cancer site, education and months from diagnosis to the first mailing of the survey were not associated with participation, although males (p  <  0.01), Hispanics and non-Hispanic blacks (p  <  0.001) were less likely to participate. 91% of survivors completing the initial survey completed the subsequent survey.DiscussionDespite the response rate, those who participated adequately reflected the population of AYA cancer survivors. The study demonstrates that cancer registries are valuable foundations for conducting observational, longitudinal population-based research on AYA cancer survivors.Implications for cancer survivorsAchieving a reasonable response rate in this population is possible, but requires extensive resources

All-codon scanning identifies p53 cancer rescue mutations

In vitro scanning mutagenesis strategies are valuable tools to identify critical residues in proteins and to generate proteins with modified properties. We describe the fast and simple All-Codon Scanning (ACS) strategy that creates a defined gene library wherein each individual codon within a specific target region is changed into all possible codons with only a single codon change per mutagenesis product. ACS is based on a multiplexed overlapping mutagenesis primer design that saturates only the targeted gene region with single codon changes. We have used ACS to produce single amino-acid changes in small and large regions of the human tumor suppressor protein p53 to identify single amino-acid substitutions that can restore activity to inactive p53 found in human cancers. Single-tube reactions were used to saturate defined 30-nt regions with all possible codon changes. The same technique was used in 20 parallel reactions to scan the 600-bp fragment encoding the entire p53 core domain. Identification of several novel p53 cancer rescue mutations demonstrated the utility of the ACS approach. ACS is a fast, simple and versatile method, which is useful for protein structure–function analyses and protein design or evolution problems

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Insights on geochemical cycling of U, Re and Mo from seasonal sampling in Boston Harbor, Massachusetts, USA

Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 71 (2007): 895-917, doi:10.1016/j.gca.2006.10.016.This study examined the removal of U, Mo, and Re from seawater by sedimentary processes at a shallow-water site with near-saturation bottom water O2 levels (240-380 μmol O2/L), very high organic matter oxidation rates (annually averaged rate is 870 μmol C/cm2/y), and shallow oxygen penetration depths (4 mm or less throughout the year). Under these conditions, U, Mo, and Re were removed rapidly to asymptotic pore water concentrations of 2.2–3.3 nmol/kg (U), 7–13 nmol/kg (Mo), and 11–14 pmol/kg (Re). The order in which the three metals were removed, determined by fitting a diffusion-reaction model to measured profiles, was Re < U < Mo. Model fits also suggest that the Mo profiles clearly showed the presence of a near-interface layer in which Mo was added to pore waters by remineralization of a solid phase. The importance of this solid phase source of pore water Mo increased from January to October as the organic matter oxidation rate increased, bottom water O2 decreased, and the O2 penetration depth decreased. Experiments with in situ benthic flux chambers generally showed fluxes of U and Mo into the sediments. However, when the overlying water O2 concentration in the chambers was allowed to drop to very low levels, Mn and Fe were released to the overlying water along with the simultaneous release of Mo and U. These experiments suggest that remineralization of Mn and/or Fe oxides may be a source of Mo and perhaps U to pore waters, and may complicate the accumulation of U and Mo in bioturbated sediments with high organic matter oxidation rates and shallow O2 penetration depths. Benthic chamber experiments including the nonreactive solute tracer, Br-, indicated that sediment irrigation was very important to solute exchange at the study site. The enhancement of sediment-seawater exchange due to irrigation was determined for the nonreactive tracer (Br-), TCO2, NH4 +, U and Mo. The comparisons between these solutes showed that reactions within and around the burrows were very important for modulating the Mo flux, but less important for U. The effect of these reactions on Mo exchange was highly variable, enhancing Mo (and, to a lesser extent, U) uptake at times of relatively modest irrigation, but inhibiting exchange when irrigation rates were faster. These results reinforce the observation that Mo can be released to and removed from pore waters via sedimentary reactions. The removal rate of U and Mo from seawater by sedimentary reactions was found to agree with the rate of accumulation of authigenic U and Mo in the solid phase. The fluxes of U and Mo determined by in situ benthic flux chamber measurements were the largest that have been measured to date. These results confirm that removal of redoxsensitive metals from continental margin sediments underlying oxic bottom water is important, and suggest that continental margin sediments play a key role in the marine budgets of these metals.We appreciate the financial support from the National Science Foundation (OCE-0220892). Funding for this work was also provided to JLM by the Postdoctoral Scholar Program at WHOI courtesy of the Cabot Marine Environmental Science Fund and the J. Seward Johnson Fund. Financial support to IMK was given by The Swedish Foundation for International Cooperation in Research and Higher Education

Predicting Positive p53 Cancer Rescue Regions Using Most Informative Positive (MIP) Active Learning

Many protein engineering problems involve finding mutations that produce proteins with a particular function. Computational active learning is an attractive approach to discover desired biological activities. Traditional active learning techniques have been optimized to iteratively improve classifier accuracy, not to quickly discover biologically significant results. We report here a novel active learning technique, Most Informative Positive (MIP), which is tailored to biological problems because it seeks novel and informative positive results. MIP active learning differs from traditional active learning methods in two ways: (1) it preferentially seeks Positive (functionally active) examples; and (2) it may be effectively extended to select gene regions suitable for high throughput combinatorial mutagenesis. We applied MIP to discover mutations in the tumor suppressor protein p53 that reactivate mutated p53 found in human cancers. This is an important biomedical goal because p53 mutants have been implicated in half of all human cancers, and restoring active p53 in tumors leads to tumor regression. MIP found Positive (cancer rescue) p53 mutants in silico using 33% fewer experiments than traditional non-MIP active learning, with only a minor decrease in classifier accuracy. Applying MIP to in vivo experimentation yielded immediate Positive results. Ten different p53 mutations found in human cancers were paired in silico with all possible single amino acid rescue mutations, from which MIP was used to select a Positive Region predicted to be enriched for p53 cancer rescue mutants. In vivo assays showed that the predicted Positive Region: (1) had significantly more (p<0.01) new strong cancer rescue mutants than control regions (Negative, and non-MIP active learning); (2) had slightly more new strong cancer rescue mutants than an Expert region selected for purely biological considerations; and (3) rescued for the first time the previously unrescuable p53 cancer mutant P152L