Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer.

BackgroundHyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA).Methods and findingsMutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression. mRNA expression levels of 1279 genes were found to be associated with pSTAT3(705) expression. Association of pSTAT3(Y705) expression with caspase-8 mRNA expression was validated by immunoblot analysis in HNSCC cells. Mutation, promoter hypermethylation, and copy number alteration of any gene were not significantly associated with increased pSTAT3(Y705) protein expression.ConclusionsThese cumulative results suggest that unbiased approaches may be useful in identifying the molecular underpinnings of oncogenic signaling, including STAT3 activation, in HNSCC. Larger datasets will likely be necessary to elucidate signaling consequences of infrequent alterations

Validation of Floating Node Method Using Three-Point Bend Doubler Under Quasi-Static Loading

The NASA Advanced Composite Project (ACP), an industry/government/university partnership, has embarked upon the task of developing technology that can aid in reducing the time line for structural certification of aircraft composite parts using a combination of technologies, one of which is high fidelity damage progression computational methods. Phase II of this project included a task for validating an approach based on the Floating Node Method combined with Directional Cohesive Elements (FNM-DCZE). This paper discusses predicted damage onset and growth in a three-point bend doubler specimen compared to experimental results. Sensitivity of the simulations to mesh refinement as well as key material properties and thermal effects are studied and reported. Overall, qualitative results suggest the main aspects of the damage progression have been captured, with the simulated damage morphology and sequence of events resembling closely what was observed experimentally. Quantitatively, the first load-peak is predicted. However, the re-loading observed in the experiments, after the first load peak, is not captured numerically, suggesting further investigation may be worth pursuing

Frequent mutation of receptor protein tyrosine phosphatases provides a mechanism for STAT3 hyperactivation in head and neck cancer

The underpinnings of STAT3 hyperphosphorylation resulting in enhanced signaling and cancer progression are incompletely understood. Loss-of-function mutations of enzymes that dephosphorylate STAT3, such as receptor protein tyrosine phosphatases, which are encoded by the PTPR gene family, represent a plausible mechanism of STAT3 hyperactivation. We analyzed whole exome sequencing (n = 374) and reverse-phase protein array data (n = 212) from head and neck squamous cell carcinomas (HNSCCs). PTPR mutations are most common and are associated with significantly increased phospho-STAT3 expression in HNSCC tumors. Expression of receptor-like protein tyrosine phosphatase T (PTPRT) mutant proteins induces STAT3 phosphorylation and cell survival, consistent with a “driver” phenotype. Computational modeling reveals functional consequences of PTPRT mutations on phospho-tyrosine–substrate interactions. A high mutation rate (30%) of PTPRs was found in HNSCC and 14 other solid tumors, suggesting that PTPR alterations, in particular PTPRT mutations, may define a subset of patients where STAT3 pathway inhibitors hold particular promise as effective therapeutic agents.Fil: Lui, Vivian Wai Yan. University of Pittsburgh; Estados UnidosFil: Peyser, Noah D.. University of Pittsburgh; Estados UnidosFil: Ng, Patrick Kwok-Shing. University Of Texas Md Anderson Cancer Center;Fil: Hritz, Jozef. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados Unidos. Masaryk University; República ChecaFil: Zeng, Yan. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Lu, Yiling. University Of Texas Md Anderson Cancer Center;Fil: Li, Hua. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Wang, Lin. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Gilbert, Breean R.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: General, Ignacio. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Bahar, Ivet. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Ju, Zhenlin. University Of Texas Md Anderson Cancer Center;Fil: Wang, Zhenghe. Case Western Reserve University; Estados UnidosFil: Pendleton, Kelsey P.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Xiao, Xiao. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Du, Yu. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Vries, John K.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados UnidosFil: Hammerman, Peter S.. Harvard Medical School; Estados UnidosFil: Garraway, Levi A.. Harvard Medical School; Estados UnidosFil: Mills, Gordon B.. University Of Texas Md Anderson Cancer Center;Fil: Johnson, Daniel E.. University of Pittsburgh at Johnstown; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Grandis, Jennifer R.. University of Pittsburgh; Estados Unidos. University of Pittsburgh at Johnstown; Estados Unido

Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells

Cells must duplicate their mass in order to proliferate. Glucose and glutamine are the major nutrients consumed by proliferating mammalian cells, but the extent to which these and other nutrients contribute to cell mass is unknown. We quantified the fraction of cell mass derived from different nutrients and found that the majority of carbon mass in cells is derived from other amino acids, which are consumed at much lower rates than glucose and glutamine. While glucose carbon has diverse fates, glutamine contributes most to protein, suggesting that glutamine's ability to replenish tricarboxylic acid cycle intermediates (anaplerosis) is primarily used for amino acid biosynthesis. These findings demonstrate that rates of nutrient consumption are indirectly associated with mass accumulation and suggest that high rates of glucose and glutamine consumption support rapid cell proliferation beyond providing carbon for biosynthesis.National Institutes of Health (U.S.) (Grant U54CA143874

Sleipner CO₂ securely stored deep beneath seabed, in spite of unexpected Hugin fracture discovery

General readers of Nature may now think that the proposition to store carbon dioxide in deep geological strata is doomed to fail (Monastersky 2013). This is far from the case, as a more balanced review could easily have pointed out. It is now important to provide an alternative perspective, based on published information, that geological storage of CO2 by deep injection for CCS is both sufficiently secure, and knowable in its environmental impacts. Furthermore, research has shown that there is good support from many parts of the public, although qualified, for CCS as an essential part of a response to the threat of global climate change and ocean acidification.General readers of Nature may now think that the proposition to store carbon dioxide in deep geological strata is doomed to fail (Monastersky 2013). This is far from the case, as a more balanced review could easily have pointed out. It is now important to provide an alternative perspective, based on published information, that geological storage of CO2 by deep injection for CCS is both sufficiently secure, and knowable in its environmental impacts. Furthermore, research has shown that there is good support from many parts of the public, although qualified, for CCS as an essential part of a response to the threat of global climate change and ocean acidification

Crossing boundaries with action research: A multinational study of school-family-community collaboration

When it began in 1990 with funds from the US Department of Education, the Center on Families, Communities, Schools, and Children's Learning established an International Network of Scholars as a forum of researchers around the world who were studying various aspects of the topic. The Center sponsored an informal journal, Unidad, and International Roundtables in the USA and Europe to promote exchange of ideas and research plans. Out of these exchanges, the idea for a multinational action research project grew. The multinational study, which began in 1992 and involved more than 40 researchers in eight projects in five countries (Australia, Chile, The Czech Republic, Portugal, and Spain), is based on the conceptual framework of the Center which views the inter-institutional connections of the school, family, and community as a set of overlapping spheres of influence on children's learning and …info:eu-repo/semantics/publishedVersio

Carbon capture and storage at the end of a lost decade

Following the landmark 2015 United Nations Paris Agreement, a growing number of countries are committing to the transition to net-zero emissions. Carbon capture and storage (CCS) has been consistently heralded to directly address emissions from the energy and industrial sectors and forms a significant component of plans to reach net-zero. However, despite the critical importance of the technology and substantial research and development to date, CCS deployment has been slow. This review examines deployment efforts over the last decade. We reveal that facility deployment must increase dramatically from current levels, and much work remains to maximize storage of CO2 in vast subsurface reserves. Using current rates of deployment, CO2 storage capacity by 2050 is projected to be around 700 million tons per year, just 10% of what is required. Meeting the net-zero targets via CCS ambitions seems unlikely unless worldwide coordinated efforts and rapid changes in policy take place

Achieving a low-carbon society: CCS expertise and opportunity in the UK

The outcome of the Paris climate talks in late 2015 was hailed as a “turning point” for international action on climate change, with 195 countries agreeing to limit the increase in average global temperatures to 1.5oC by the end of this century. It is an ambitious and necessary goal, but is it achievable? An increasing emphasis on clean, renewable energy is essential, as are more efficient ways of using energy. However, the best of intentions will hit an insurmountable roadblock if we continue to burn fossil fuels without deploying Carbon Capture and Storage (CCS). CCS is a chain of proven technologies that can take us all the way to a zero-carbon future. For many economies that will be reliant on fossil fuels for several decades, CCS can support a gradual phasing in of renewable energy. CCS remains the only path to deep cuts in carbon emissions from products such as cement, steel and fertiliser - even whisky - and will effectively decarbonise power and heat generation. Deployed on gas or sustainable biomass power, it can plug the gaps in the intermittency of power supply from renewables. And there are many studies that show that the UK and its assets are best placed to deliver CCS for the whole of Europe. Although CCS is already operating in other parts of the world, this climate change technology has had a tough time making progress in the UK. The latest blow came in the last quarter of 2015, within days of the Paris talks. Two major UK CCS projects were poised to begin construction after completing front-end engineering and design (FEED) studies. Without warning, anticipated funding from the UK Government's £1 billion CCS Commercialisation Competition was withdrawn before these studies had been submitted. The Peterhead CCS Project, set to become the world's first CCS project on gas power, and White Rose, which would demonstrate oxyfuel with CCS technology on coal power, have had little choice but to consider closure. In the aftermath of the COP21 climate deal, and with the UK's own climate change advisers restating the importance of the technology in meeting the UK's Fifth Carbon Budget, the case for CCS remains as cogent as ever. In the UK, we have access to an immense CO2 storage asset beneath the North Sea, which could contain a century of Europe's carbon emissions. Added to that is an impressive track record of world-leading research and development (R&D), decades of oil and gas industry knowledge and skills and an infrastructure facing decommissioning that can be repurposed to put carbon back below ground. The progress and potential of CCS in the UK is much more than a government competition. This report describes why we need to get one of the most obvious and effective climate change tools back on track and highlights the strengths of and opportunities for the UK - and Scotland, in particular.The outcome of the Paris climate talks in late 2015 was hailed as a “turning point” for international action on climate change, with 195 countries agreeing to limit the increase in average global temperatures to 1.5oC by the end of this century. It is an ambitious and necessary goal, but is it achievable? An increasing emphasis on clean, renewable energy is essential, as are more efficient ways of using energy. However, the best of intentions will hit an insurmountable roadblock if we continue to burn fossil fuels without deploying Carbon Capture and Storage (CCS). CCS is a chain of proven technologies that can take us all the way to a zero-carbon future. For many economies that will be reliant on fossil fuels for several decades, CCS can support a gradual phasing in of renewable energy. CCS remains the only path to deep cuts in carbon emissions from products such as cement, steel and fertiliser - even whisky - and will effectively decarbonise power and heat generation. Deployed on gas or sustainable biomass power, it can plug the gaps in the intermittency of power supply from renewables. And there are many studies that show that the UK and its assets are best placed to deliver CCS for the whole of Europe. Although CCS is already operating in other parts of the world, this climate change technology has had a tough time making progress in the UK. The latest blow came in the last quarter of 2015, within days of the Paris talks. Two major UK CCS projects were poised to begin construction after completing front-end engineering and design (FEED) studies. Without warning, anticipated funding from the UK Government's £1 billion CCS Commercialisation Competition was withdrawn before these studies had been submitted. The Peterhead CCS Project, set to become the world's first CCS project on gas power, and White Rose, which would demonstrate oxyfuel with CCS technology on coal power, have had little choice but to consider closure. In the aftermath of the COP21 climate deal, and with the UK's own climate change advisers restating the importance of the technology in meeting the UK's Fifth Carbon Budget, the case for CCS remains as cogent as ever. In the UK, we have access to an immense CO2 storage asset beneath the North Sea, which could contain a century of Europe's carbon emissions. Added to that is an impressive track record of world-leading research and development (R&D), decades of oil and gas industry knowledge and skills and an infrastructure facing decommissioning that can be repurposed to put carbon back below ground. The progress and potential of CCS in the UK is much more than a government competition. This report describes why we need to get one of the most obvious and effective climate change tools back on track and highlights the strengths of and opportunities for the UK - and Scotland, in particular

Otoferlin is a calcium sensor that directly regulates SNARE-mediated membrane fusion

Mutations in otoferlin are linked to human hearing loss. New research defines a function for this C2 domain–containing protein in synaptic vesicle exocytosis in cochlear hair cells

International home economics

The conference was planned to serve the interests of those who wish to work in home economics programs abroad and those who are concerned with the education of international students in the universities and colleges of the United States. Approximately 165 home economists from other states and from foreign countries I including the African and Latin American countries I participated in the conference.https://lib.dr.iastate.edu/card_reports/1026/thumbnail.jp