An Architecture for Scaling NVO Services to TeraGrid

The term "cyberinfrastructure" has been adopted by the US National Science Foundation to mean "advanced computing engines, data archives and digital libraries, observation and sensor systems, and other research and education instrumentation [linked] into a common framework". One of the largest awards in this program is the TeraGrid, a linkage of large supercomputer centers based on the Globus software. Another cyberinfrastructure program is the National Virtual Observatory, a linkage of astronomical data publishers into a service-oriented framework. There are different philosophies behind the TeraGrid and the NVO architecture. This note explains a proposed service-oriented architecture for TeraGrid nodes that is an attempt to bridge these ways of working, and a prototype instantiation at Caltech

Missouri crop-share leasing patterns (1999)

This guide focuses on one specific rental agreement, the crop-share lease. This guide uses producer survey information to determine how tenants and landowners share the costs of production under 50-50 and 2/3- 1/3 lease agreements. A 2/3- 1/3 crop-share arrangement apportions two-thirds of the crop to the tenant and one-third to the landowner.New 7/99/5M

Livestock gross margin (LGM) insurance in Missouri (2014)

In livestock production, gross margin is the difference between revenue from livestock or milk sales and feed costs. It is an indicator of profitability. Livestock gross margin (LGM) insurance offers livestock producers a way to manage gross margin risk by guaranteeing a minimum gross margin. If the gross margin guarantee at the beginning of the contract period is higher than the actual gross margin at the end of the contract period, the policyholder earns an indemnity. LGM insurance protects expected gross margin rather than a selling price, which is what livestock risk protection (LRP) insurance is for. It does not protect against risks such as disease or death.New 6/14/Web

Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration.

Nematode EAK-7 (enhancer-of-akt-1-7) regulates dauer formation and controls life span; however, the function of the human ortholog mammalian EAK-7 (mEAK-7) is unknown. We report that mEAK-7 activates an alternative mechanistic/mammalian target of rapamycin (mTOR) signaling pathway in human cells, in which mEAK-7 interacts with mTOR at the lysosome to facilitate S6K2 activation and 4E-BP1 repression. Despite interacting with mTOR and mammalian lethal with SEC13 protein 8 (mLST8), mEAK-7 does not interact with other mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2) components; however, it is essential for mTOR signaling at the lysosome. This phenomenon is distinguished by S6 and 4E-BP1 activity in response to nutrient stimulation. Conventional S6K1 phosphorylation is uncoupled from S6 phosphorylation in response to mEAK-7 knockdown. mEAK-7 recruits mTOR to the lysosome, a crucial compartment for mTOR activation. Loss of mEAK-7 results in a marked decrease in lysosomal localization of mTOR, whereas overexpression of mEAK-7 results in enhanced lysosomal localization of mTOR. Deletion of the carboxyl terminus of mEAK-7 significantly decreases mTOR interaction. mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration

mEAK-7 Forms an Alternative mTOR Complex with DNA-PKcs in Human Cancer.

MTOR associated protein, eak-7 homolog (mEAK-7), activates mechanistic target of rapamycin (mTOR) signaling in human cells through an alternative mTOR complex to regulate S6K2 and 4E-BP1. However, the role of mEAK-7 in human cancer has not yet been identified. We demonstrate that mEAK-7 and mTOR signaling are strongly elevated in tumor and metastatic lymph nodes of patients with non-small-cell lung carcinoma compared with those of patients with normal lung or lymph tissue. Cancer stem cells, CD44+/CD90+ cells, yield elevated mEAK-7 and activated mTOR signaling. mEAK-7 is required for clonogenic potential and spheroid formation. mEAK-7 associates with DNA-dependent protein kinase catalytic subunit isoform 1 (DNA-PKcs), and this interaction is increased in response to X-ray irradiation to regulate S6K2 signaling. DNA-PKcs pharmacologic inhibition or genetic knockout reduced S6K2, mEAK-7, and mTOR binding with DNA-PKcs, resulting in loss of S6K2 activity and mTOR signaling. Therefore, mEAK-7 forms an alternative mTOR complex with DNA-PKcs to regulate S6K2 in human cancer cells

Forage crop irrigation systems and economics (2013)

"Agriculture."Irrigation presents an opportunity for Missouri forage producers to mitigate production risk from drought. This guide explores three areas to consider before choosing a forage irrigation system: expected forage response, equipment options and the economics of irrigating forage.New 11/13/Web

Initial experience of dedicated breast PET imaging of ER+ breast cancers using [F-18]fluoroestradiol.

Dedicated breast positron emission tomography (dbPET) is an emerging technology with high sensitivity and spatial resolution that enables detection of sub-centimeter lesions and depiction of intratumoral heterogeneity. In this study, we report our initial experience with dbPET using [F-18]fluoroestradiol (FES) in assessing ER+ primary breast cancers. Six patients with >90% ER+ and HER2- breast cancers were imaged with dbPET and breast MRI. Two patients had ILC, three had IDC, and one had an unknown primary tumor. One ILC patient was treated with letrozole, and another patient with IDC was treated with neoadjuvant chemotherapy without endocrine treatment. In this small cohort, we observed FES uptake in ER+ primary breast tumors with specificity to ER demonstrated in a case with tamoxifen blockade. FES uptake in ILC had a diffused pattern compared to the distinct circumscribed pattern in IDC. In evaluating treatment response, the reduction of SUVmax was observed with residual disease in an ILC patient treated with letrozole, and an IDC patient treated with chemotherapy. Future study is critical to understand the change in FES SUVmax after endocrine therapy and to consider other tracer uptake metrics with SUVmax to describe ER-rich breast cancer. Limitations include variations of FES uptake in different ER+ breast cancer diseases and exclusion of posterior tissues and axillary regions. However, FES-dbPET has a high potential for clinical utility, especially in measuring response to neoadjuvant endocrine treatment. Further development to improve the field of view and studies with a larger cohort of ER+ breast cancer patients are warranted

The prevalence of hepatitis C virus among people of South Asian origin in Glasgow: results from a community based survey and laboratory surveillance

Background South Asians often present late with HCV or HBV related liver disease which could have been avoided with early diagnosis and subsequent treatment; however the prevalence of HCV/HBV among South Asians in Glasgow is not known. Accordingly, to inform the need for case finding among this group we aimed to examine the prevalence of Hepatitis C virus (HCV) among South Asians living in Glasgow. Methods A community-based survey recruited individuals at six mosques and four community centres serving the South Asian community during 2009-2010; participants had predominantly never been HCV tested. Laboratory surveillance data involving all individuals tested for HCV during 1993-2009 were examined and South Asians were identified using Nam Pehchan software. Results In the community-based survey, 2.6% of 1288 participants tested HCV-antibody positive; the prevalence ranged from 0.6% among those born in the UK to 3.1% among those born in Pakistan. The odds of testing HCV-antibody positive were significantly raised among those who had surgery in South Asia (aOR: 5.0, 95% CI: 2.0-12.3) and had either medical/dental treatment or an injection in South Asia (aOR: 2.2, 95% CI: 1.0-5.0). Of 6404 South Asians identified from laboratory surveillance data, 9.3% tested HCV positive. An estimated 38% (330/870) of HCV-infected South Asians living in Glasgow remain undiagnosed. Conclusions South Asians living in Glasgow, particularly those born outside the UK are at greater risk of HCV infection than the general population. Efforts to increase awareness and testing in this population are warranted.</p

User preferences and willingness to pay for safe drinking water: Experimental evidence from rural Tanzania.

Almost half of all deaths from drinking microbiologically unsafe water occur in Sub-Saharan Africa. Household water treatment and safe storage (HWTS) systems, when consistently used, can provide safer drinking water and improve health. Social marketing to increase adoption and use of HWTS depends both on the prices of and preferences for these systems. This study included 556 households from rural Tanzania across two low-income districts with low-quality water sources. Over 9 months in 2012 and 2013, we experimentally evaluated consumer preferences for six "low-cost" HWTS options, including boiling, through an ordinal ranking protocol. We estimated consumers' willingness to pay (WTP) for these options, using a modified auction. We allowed respondents to pay for the durable HWTS systems with cash, chickens or mobile money; a significant minority chose chickens as payment. Overall, our participants favored boiling, the ceramic pot filter and, where water was turbid, PuR™ (a combined flocculant-disinfectant). The revealed WTP for all products was far below retail prices, indicating that significant scale-up may need significant subsidies. Our work will inform programs and policies aimed at scaling up HWTS to improve the health of resource-constrained communities that must rely on poor-quality, and sometimes turbid, drinking water sources

Insight into the Brain-Specific Alpha Isoform of the Scaffold Protein SH2B1 and its Rare Obesity-Associated Variants

Obesity poses a major health problem since it increases the risk for type 2 diabetes, metabolic syndrome, heart disease, and cancer. Mutations in SH2B1 have been identified in patients exhibiting severe childhood obesity and insulin resistance. Mice deficient in SH2B1 exhibit a similar phenotype to the patients, suggesting an important role for SH2B1 in regulating energy homeostasis. SH2B1 is alternatively spliced, leading to four isoforms (alpha, beta, gamma, and delta) that share an N-terminal 631 amino acids but have unique C-terminal tails. The findings that all SH2B1 isoforms are expressed in the brain and neuronal expression of SH2B1 beta rescues the obese phenotype in SH2B1-deficient mice suggest that SH2B1 plays an important function in neurons. In further support of a neuronal function for SH2B1, SH2B1 enhances neurotrophic factor-induced neurite outgrowth and the human obesity-associated mutations impair the ability of SH2B1 to promote neurite outgrowth. To gain insight into critical functions of SH2B1, its isoforms, and the human obesity-associated mutations, the work in this thesis characterizes the ability of rare SH2B1 mutations associated with human obesity both shared by all isoforms and those specific to SH2B1 alpha to affect cellular actions of SH2B1. It further examines how the unique C-terminal tails of SH2B1 regulate the actions of the shared 631 N-terminal amino acids of SH2B1. Our collaborator I. S. Farooqi identified variants in SH2B1 encoding for R227C, G238C, R270W, E299G, or T546A and the SH2B1 alpha-specific mutations A663V, V695M, or A723V in individuals with severe-early onset obesity and insulin resistance. We determined that like SH2B1 beta, SH2B1 alpha enhanced growth hormone-stimulated motility of macrophages and the mutations T546A, A663V and A723V impaired that enhancement. Unlike SH2B1 beta, SH2B1 alpha was unable to enhance NGF-mediated neurite outgrowth and the mutations in SH2B1 alpha had no impact. However, mutations G238C, R270W, E299G and T546A impaired SH2B1 beta-enhancement of NGF-induced neurite outgrowth. This led us to conclude that variants can disrupt specific isoform function, suggesting novel regulatory roles in SH2B1 isoform function. The discrepancy between SH2B1 alpha and beta regulation of neurite outgrowth directed us to ask how the unique C-terminal tails of the alpha and beta isoforms affect the ability of SH2B1 to regulate NGF-induced neurite outgrowth. By comparing the actions of SH2B1 alpha and beta to those of the N-terminal 631 amino acids shared by all isoforms of SH2B1, we found that the alpha tail prevents: 1) the ability of SH2B1 to cycle through the nucleus, and 2) SH2B1 enhancement of NGF-induced neurite outgrowth, gene expression, and phosphorylation of NGF-receptor, TrkA, and downstream signaling proteins Akt and PLC gamma. These functions were restored when Tyr753 in the alpha tail was mutated to Phe, suggesting that phosphorylation of Tyr753 regulates SH2B1 alpha function. We provide evidence that TrkA phosphorylates Tyr55 and Tyr439 in both SH2B1 alpha and SH2B1 beta, and Tyr753 in SH2B1 alpha. Finally, co-expression of SH2B1 alpha inhibits the ability of SH2B1 beta to enhance NGF-induced neurite outgrowth. These results suggest that the C-terminal tails of SH2B1 isoforms are key determinants of their cellular roles and are regulated by phosphorylation. By providing valuable information about how seemingly minor differences between isoforms can have a profound impact on the function of that protein, my studies also provide important insight into the impact of differential splicing on neuron function.PHDCellular & Molecular BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/137175/1/raymjoe_1.pd