A spectral collocation technique based on integrated Chebyshev polynomials for biharmonic problems in irregular domains

In this paper, an integral collocation approach based on Chebyshev polynomials for numerically solving biharmonic equations [N. Mai-Duy, R.I. Tanner, A spectral collocation method based on integrated Chebyshev polynomials for biharmonic boundary-value problems, J. Comput. Appl. Math. 201 (1) (2007) 30–47] is further developed for the case of irregularly shaped domains. The problem domain is embedded in a domain of regular shape, which facilitates the use of tensor product grids. Two relevant important issues, namely the description of the boundary of the domain on a tensor product grid and the imposition of double boundary conditions, are handled effectively by means of integration constants. Several schemes of the integral collocation formulation are proposed, and their performances are numerically investigated through the interpolation of a function and the solution of 1D and 2D biharmonic problems. Results obtained show that they yield spectral accuracy

The Future of Aging in the Town of Brewster: Brewster Council on Aging Needs Assessment Study

This report describes efforts undertaken by the Town of Brewster Council on Aging, in partnership with the Center for Social and Demographic Research on Aging within the Gerontology Institute at the University of Massachusetts Boston, to investigate the needs, interests, preferences, and opinions of Brewster’s older population. The focus of this report is on two cohorts of Brewster’s residents — those aged 45 to 59, and the cohort of individuals who are currently aged 60 and over (“seniors”). The content of this report is intended to inform the Town of Brewster, the Brewster Council on Aging, and organizations that provide services to older residents, as well as those who advocate for older people, and community members at large

Aging in Barnstable: Striving for High Livability in a Cape Cod Community

This report describes collaborative efforts undertaken by the Town of Barnstable Senior Services Division and the Center for Social and Demographic Research on Aging, within the Gerontology Institute at the McCormack Graduate School, University of Massachusetts Boston. Beginning in Fall 2014, these organizations partnered to conduct a study to investigate the needs, interests, preferences, and opinions of the Town’s older resident population, with respect to living and aging in Barnstable. The focus of this report was on two cohorts of Barnstable residents — those aged 50 to 59 (referred to as “Boomers”), and the cohort of individuals who are currently aged 60 and over (“Seniors”)

Needs Assessment for Littleton Elder and Human Services and the Council on Aging

This report describes efforts undertaken by the Town of Littleton Council on Aging, in partnership with the Center for Social and Demographic Research on Aging within the Gerontology Institute at the University of Massachusetts Boston, to investigate the needs, interests, preferences, and opinions of Littleton’s older population. The focus of this report was on two cohorts of Littleton residents—those aged 50 to 59 (referred to as “Boomers”), and the cohort of individuals who are currently aged 60 and over (“Seniors”). The content of this report is intended to inform the Town of Littleton, the Littleton Council on Aging and Senior Center, and organizations that provide services to older residents, as well as those who advocate for older people, and community members at large

Mass Azithromycin Distribution and Community Microbiome: A Cluster-Randomized Trial.

BackgroundMass distributions of oral azithromycin have long been used to eliminate trachoma, and they are now being proposed to reduce childhood mortality. The observed benefit appears to be augmented with each additional treatment, suggesting a possible community-level effect. Here, we assess whether 2 biannual mass treatments of preschool children affect the community's gut microbiome at 6 months after the last distribution.MethodsIn this cluster-randomized controlled trial, children aged 1-60 months in the Dossa region of Niger were randomized at the village level to receive a single dose of azithromycin or placebo every 6 months. Fecal samples were collected 6 months after the second treatment for metagenomic deep sequencing. The prespecified primary outcome was the Euclidean PERMANOVA of the gut microbiome, or effectively the distance between the genus-level centroid at the community level, with the secondary outcome being the Simpson's α diversity.ResultsIn the azithromycin arm, the gut microbial structures were significantly different than in the placebo arm (Euclidean PERMANOVA, P < .001). Further, the diversity of the gut microbiome in the azithromycin arm was significantly lower than in the placebo arm (inverse Simpson's index, P = .005).ConclusionsTwo mass azithromycin administrations, 6 months apart, in preschool children led to long-term alterations of the gut microbiome structure and community diversity. Here, long-term microbial alterations in the community did not imply disease but were associated with an improvement in childhood mortality.Clinical trials registrationNCT02048007

Age-Friendly Yarmouth Needs Assessment Report

Communities throughout the nation are pursuing new strategies to promote health and quality of life among their residents. In 2014, the Town of Yarmouth joined the Age-Friendly Network through the World Health Organization and embarked on a five-year process to evaluate the community’s age-friendly features, plan for improvements, and implement change. The primary purpose of this report is to describe findings developed as part of the initial needs assessment phase of Yarmouth’s age-friendly initiative

Assessing Current and Future Needs of Residents Aging in the Town of Andover

This report describes the collaborative efforts undertaken by the Town of Andover Division of Elder Services and the Center for Social and Demographic Research on Aging, within the McCormack Graduate School at the University of Massachusetts Boston. Beginning in Fall 2014, these organizations joined to conduct a needs assessment to investigate the needs, interests, preferences and opinions of the Town’s older resident population, with respect to aging in Andover. The focus of this report is on two cohorts of Andover residents—those who are age 50 to 59 (referred to as “Boomers”) and the cohort of individuals who are currently age 60 and older (“Seniors”). Within the older cohort of Seniors, we also conducted selected analyses on subgroups (e.g., ages 60 to 79; 60 to 69; 70 to 79; and 80 and older) to highlight important differences by age group. During this assessment, several research methods were utilized in order to sketch a multidimensional image of the Town’s older residents that could be used to plan and implement current and future services for older residents in Andover. We began the process by examining public data from the U.S. Census Bureau to describe basic demographic characteristics, as well as economic characteristics, disability status, and living situations of older people in the Town. Early in the project we invited Town residents to attend a community forum, to better understand how residents perceive current and future aging-related needs of the Town. We used information gathered at this meeting to develop a survey instrument to be administered to a randomly selected sample of residents from both age cohorts. We conducted two focus groups to obtain feedback from various stakeholders who regularly interact with older residents, regarding issues and concerns about aging in Andover. We conducted interviews with four key stakeholders to acquire input from local experts on the implications of the aging population, and the functioning of the Center at Punchard. We produced three maps depicting town resources that are perceived as assets to aging in place in Andover by older adult residents. Finally, we conducted a comparison of Senior Centers in three towns that are similar to Andover to assess how needs of older adults are met in other nearby communities. Collectively, the content of this report is intended to inform the Andover Division of Elder Services and the Center at Punchard, along with other offices within the Town with a stake in the aging of Andover, and organizations that provide services to older residents, as well as those who advocate for older people, and community members at large

Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1)

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization

Cudraflavone C induces tumor-specific apoptosis in colorectal cancer cells through inhibition of the phosphoinositide 3-kinase (PI3K)-AKT pathway

Cudraflavone C (Cud C) is a naturally-occurring flavonol with reported anti-proliferative activities. However, the mechanisms by which Cud C induced cytotoxicity have yet to be fully elucidated. Here, we investigated the effects of Cud C on cell proliferation, caspase activation andapoptosis induction in colorectal cancer cells (CRC). We show that Cud C inhibits cell proliferation in KM12, Caco-2, HT29, HCC2998, HCT116 and SW48 CRC but not in the non-transformed colorectal epithelial cells, CCD CoN 841. Cud C induces tumorselective apoptosis via mitochondrial depolarization and activation of the intrinsic caspase pathway. Gene expression profiling by microarray analyses revealed that tumor suppressor genes EGR1, HUWE1 and SMG1 were significantly up-regulated while oncogenes such as MYB1, CCNB1 and GPX2 were down-regulated following treatment with Cud C. Further analyses using Connectivity Map revealed that Cud C induced a gene signature highly similar to that of protein synthesis inhibitors and phosphoinositide 3-kinase (PI3K)-AKT inhibitors, suggesting that Cud C might inhibit PI3K-AKT signaling. A luminescent cell free PI3K lipid kinase assay revealed that Cud C significantly inhibited p110?/p85? PI3K activity, followed by p120?, p110?/p85?, and p110?/p85? PI3K activities. The inhibition by Cud C on p110?/p85? PI3K activity was comparable to LY-294002, a known PI3K inhibitor. Cud C also inhibited phosphorylation of AKT independent of NF?B activity in CRC cells, while ectopic expression of myristoylated AKT completely abrogated the anti-proliferative effects, and apoptosis induced by Cud C in CRC. These findings demonstrate that Cud C induces tumor-selective cytotoxicity by targeting the PI3K-AKT pathway. These findings provide novel insights into the mechanism of action of Cud C, and indicate that Cud C further development of Cud C derivatives as potential therapeutic agents is warranted