Identifying Senescence as a Mode of Chemo Resistance in Ovarian Cancer

Current treatments of ovarian and breast cancer result in chemo resistance all too often. It has been hypothesized that senescence-a dormant condition associated with increased age and apoptosis- may play a role in the development of chemo resistance. We performed an in-vitro study with HOSE (carboplatin-sensitive), SKOV3 (chemo resistant ovarian cancer), and CAMA1 (chemo resistant breast cancer) cell lines, which were exposed to a variety of platinum-based treatments meant to model current cover clinically relevant scenarios in terms of tumor hypoxia. They were then stained for senescence in-vitro using B-gal, and analyzed for proliferation using the Cell Counting Kit 8, trypan blue dye exclusion, and survival plating, among other methods. Real-time quantitative PCR was used to determine relative levels of gene expression for classical apoptotic and senescent markers. Our results indicate that proliferation was temporarily halted in SKOV3 and CAMA1 after treatment. Cell proliferation later resumed in these cell lines while HOSE cell underwent apoptosis. Analysis of genetic tests (such as qPCR) also revealed that SKOV3 and CAMA1 had decreased gene expression of key genes that regulate apoptosis and senescence (such as p53 and CDK2). It can be concluded from this data that senescence was in fact a mode of chemoresistance and that future treatments may want to focus on disabling cancerous cells’ senescent stage

Tapping Environmental History to Recreate America’s Colonial Hydrology

To properly remediate, improve, or predict how hydrological systems behave, it is vital to establish their histories. However, modern-style records, assembled from instrumental data and remote sensing platforms, hardly exist back more than a few decades. As centuries of data is preferable given multidecadal fluxes of both meteorology/climatology and demographics, building such a history requires resources traditionally considered only useful in the social sciences and humanities. In this Feature, Pastore et al. discuss how they have undertaken the synthesis of historical records and modern techniques to understand the hydrology of the Northeastern U.S. from Colonial times to modern day. Such approaches could aid studies in other regions that may require heavier reliance on qualitative narratives. Further, a better insight as to how historical changes unfolded could provide a “past is prologue” methodology to increase the accuracy of predictive environmental models

The AllWISE Motion Survey, Part 2

We use the AllWISE Data Release to continue our search for WISE-detected motions. In this paper, we publish another 27,846 motion objects, bringing the total number to 48,000 when objects found during our original AllWISE motion survey are included. We use this list, along with the lists of confirmed WISE-based motion objects from the recent papers by Luhman and by Schneider et al. and candidate motion objects from the recent paper by Gagne et al. to search for widely separated, common-proper-motion systems. We identify 1,039 such candidate systems. All 48,000 objects are further analyzed using color-color and color-mag plots to provide possible characterizations prior to spectroscopic follow-up. We present spectra of 172 of these, supplemented with new spectra of 23 comparison objects from the literature, and provide classifications and physical interpretations of interesting sources. Highlights include: (1) the identification of three G/K dwarfs that can be used as standard candles to study clumpiness and grain size in nearby molecular clouds because these objects are currently moving behind the clouds, (2) the confirmation/discovery of several M, L, and T dwarfs and one white dwarf whose spectrophotometric distance estimates place them 5-20 pc from the Sun, (3) the suggestion that the Na 'D' line be used as a diagnostic tool for interpreting and classifying metal-poor late-M and L dwarfs, (4) the recognition of a triple system including a carbon dwarf and late-M subdwarf, for which model fits of the late-M subdwarf (giving [Fe/H] ~ -1.0) provide a measured metallicity for the carbon star, and (5) a possible 24-pc-distant K5 dwarf + peculiar red L5 system with an apparent physical separation of 0.1 pc.Comment: 62 pages with 80 figures, accepted for publication in The Astrophysical Journal Supplement Series, 23 Mar 2016; second version fixes a few small typos and corrects the footnotes for Table

A description of a tailored knowledge translation intervention delivered by knowledge brokers within public health departments in Canada

BACKGROUND:While there is an expectation to demonstrate evidence-informed public health there is an ongoing need for capacity development. The purpose of this paper is to provide a description of a tailored knowledge translation intervention implemented by knowledge brokers (KBs), and reflections on the factors that facilitated or hindered its implementation. METHODS:The 22-month knowledge translation intervention, implemented by two KBs, sought to facilitate evidence-informed public health decision-making. Data on outcomes were collected using a knowledge, skills and behavioural assessment survey. In addition, the KBs maintained reflective journals noting which activities appeared successful or not, as well as factors related to the individual or the organisation that facilitated or hindered evidence-informed decision-making. RESULTS:Tailoring of the knowledge translation intervention to address the needs, preferences and structure of each organisation resulted in three unique interventions being implemented. A consistent finding across organisations was that each site needed to determine where evidence-informed decision-making 'fit' within pre-existing organisational processes. Components of the intervention consistent across the three organisations included one-to-one mentoring of teams through rapid evidence reviews, large group workshops and regular meetings with senior management. Components that varied included the frequency of the KB being physically onsite, the amount of time staff spent with the KB and proportion of time spent one-to-one with a KB versus in workshops. Key facilitating factors for implementation included strong leadership, influential power of champions, supportive infrastructure, committed resources and staff enthusiasm. CONCLUSIONS:The results of this study illustrate the importance of working collaboratively with organisations to tailor knowledge translation interventions to best meet unique needs, preferences, organisational structures and contexts. Organisational factors such as leadership, champions and supportive infrastructure play a key role in determining the impact of the knowledge translation interventions. Future studies should explore how these factors can be fostered and/or developed within organisations. While KBs implemented the knowledge translation intervention in this study, more research is needed to understand the impact of all change agent roles including KBs, as well as how these roles can be maintained in the long-term if proven effective.Funder: Institute of Population and Public Health; Grant(s): 10186717pubpu

Pre-Hispanic anthropogenic wetlands in the upper Ica drainage, south-central Andes: dating and context

Humans have engineered their environmentsthroughout the Holocene, especially in the constructionof hydraulic infrastructure. In many regions,however, this infrastructure is difficult to date, includingthe vestiges of water-management systems in theAndean highlands. Focusing on silt reservoirs in theupper Ica drainage, Peru, the authors use cores andradiocarbon dates to demonstrate the pre-Hispanicconstruction of walls to enhance and expand wetlandsfor camelid pasture. Interventions dated to the Incaperiod (AD 1400?1532) indicate an intensificationof investment in hydraulic infrastructure to expandproduction capacity in support of the state. Theresults are discussed in the context of the hydraulicstrategies of other states and empires.Fil: Lane, Kevin John. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto de las Culturas. Universidad de Buenos Aires. Instituto de las Culturas; ArgentinaFil: Beresford Jones, David. Universitat Bonn; AlemaniaFil: Coll, Luis Vicente Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto de las Culturas. Universidad de Buenos Aires. Instituto de las Culturas; ArgentinaFil: Marsh, Erik Johnson. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Scaife, Rob. University of Southampton; Reino UnidoFil: Greco Mainero, Mariano Catriel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales; ArgentinaFil: Oros, Oliver Huaman. Ministerio de Cultura; PerúFil: Herrera, Alexander. Universidad de Los Andes; ColombiaFil: Grant Lett Brown, Jennifer Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Secretaría de Cultura de la Nación. Dirección Nacional de Cultura y Museos. Instituto Nacional de Antropología y Pensamiento Latinoamericano; ArgentinaFil: French, Charles. University of Cambridge; Estados Unido

Co-development and piloting of a menstrual, sexual and reproductive health intervention to improve social and psychological outcomes among secondary schoolgirls in Northern Tanzania: the PASS MHW study protocol.

INTRODUCTION: Poor menstrual health negatively impacts psychosocial and physical health, and subsequently leads to poor school outcomes, but the effort to improve adolescent girls' menstrual health in Tanzania remains fragmented. This study aimed to develop and pilot a scalable, comprehensive menstrual, sexual and reproductive health (MSRH) intervention within Tanzanian government structures to improve MSRH practices and perceptions and the overall school climate to ensure the psychosocial well-being and optimal school participation and performance among secondary schoolgirls. METHODS AND ANALYSIS: This study will be conducted in three phases. Phase I will be a formative research to iteratively refine an existing puberty and menstrual health intervention, and to collaboratively design strategies to embed the intervention into government structures thereby promoting scalability. In Phase II, we will pilot and evaluate the refined intervention and implementation strategies using a mixed-methods design to assess (1) feasibility, acceptability and sustainability; and (2) effect on MSRH practices and perceptions and the overall school climate. In Phase III, we will synthesise the research findings in collaboration with the national, regional and district government and non-government stakeholders. ETHICS AND DISSEMINATION: This pilot study will provide evidence-based recommendations for a comprehensive, complex menstrual and puberty intervention within secondary schools in Tanzania that can be further tested for broader effectiveness across a larger population. Papers, policy briefs and both regional/international conference presentations are planned to reach academic and non-academic groups. Protocol, tools and consent have been reviewed and approved by the independent Tanzanian national ethics committee (NIMR/HQ/R.8a/Vol.IX/3647) and the LSHTM Observational/Interventions Research Ethics Committee (LSHTM Ethics Ref: 22854). The project will involve adolescents, and procedures will be followed to ensure that we obtain permission and consent of parents and guardians and assent from all adolescents below 18 years of age that will be enrolled in the study

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio

Unexpected Long-Term Variability in Jupiter's Tropospheric Temperatures

An essential component of planetary climatology is knowledge of the tropospheric temperature field and its variability. Previous studies of Jupiter hinted at periodic behavior that was non-seasonal, as well as dynamical relationships between tropospheric and stratospheric temperatures. However, these observations were made over time frames shorter than Jupiter's orbit or they used sparse sampling. We derived upper-tropospheric (300-mbar) temperatures over 40 years, extending those studies to cover several orbits of Jupiter, revealing unexpected results. Periodicities of 4, 7 8-9 and 10-14 years were discovered that involved different latitude bands and seem disconnected from seasonal changes in solar heating. Anti-correlations of variability in opposite hemispheres were particularly striking at 16, 22 and 30 degrees from the equator. Equatorial temperature variations are also anticorrelated with those 60-70 km above. Such behavior suggests a top-down control of equatorial tropospheric temperatures from stratospheric dynamics. Realistic future global climate models must address the origins of these variations in preparation for their extension to a wider array of gas-giant exoplanets.Comment: Primary file: 16 pages, 5 figures. Supplemental File (attached): 12 pages, 3 figures, 1 tabl