10,818 research outputs found
Indium adhesion provides quantitative measure of surface cleanliness
Indium tipped probe measures hydrophobic and hydrophilic contaminants on rough and smooth surfaces. The force needed to pull the indium tip, which adheres to a clean surface, away from the surface provides a quantitative measure of cleanliness
Gathering and Transporting Marcellus and Utica Shale Natural Gas to the Market and the Regulation of Midstream Pipeline Companies - The Case for a Uniform Federal and State Definition of Gathering in the Context of Economic and Siting Regulation
Much has been written about the major natural gas reserves in the Marcellus and even Utica Shale formations located in West Virginia, Pennsylvania, and Ohio. But much of the focus has been on the law and regulation around producing the gas-drilling and getting it out of the ground. Related, but serving a very different function, is the role of pipeline companies in their various business models to transport that gas to market. This is a different and equally robust and growing segment of the natural gas industry where large amounts of shale exploration take place. In fact, without pipelines and regulatory certainty for those constructing pipelines, natural gas has no value as it cannot be transported to the market place in any practical manner without pipelines. When planning to construct or acquire natural gas pipelines, a major question to consider is, Will the pipelines be regulated? For purposes of this Article, regulated refers to regulation of the siting and construction of pipeline facilities as well as economic regulation of the prices (or rates) charged and the terms and conditions (or tariffs) for services offered to customers (or shippers) transporting on those pipelines. Depending upon the physical configuration of the pipelines, the manner in which they are used to transport natural gas, and the type of customer transporting the gas on the pipeline, the correct answer could be (1) no regulation, (2) regulation by a state or commonwealth public service or utility commission, or (3) possible regulation by the Federal Energy Regulatory Commission ( FERC ). Moreo- ver, with respect to state or commonwealth regulation, as one might imagine, the extent of that regulation varies by state or commonwealth
BRCA1 & CTDP1 BRCT Domainomics in the DNA Damage Response
Genomic instability is one of the enabling characteristics of cancer. DNA damage response pathways are important for genomic integrity and cell cycle progression. Defects in DNA damage repair can often lead to cell cycle arrest, cell death, or tumorigenesis. The activation of the DNA damage response includes tightly regulated signaling cascades that involve kinase phosphorylation and modular domains that scaffold phosphorylated motifs to coordinate recruitment of DNA repair proteins. Modular domains are conserved tertiary structures of a protein that can fold, function, and evolve independently from an intact protein. One of the most common modular domains involved in DNA damage repair is the BRCA1 C-Terminal (BRCT) domain. The BRCT domain is approximately 90-100 amino acids long and functions as a scaffolding domain to help recruit DNA damage-related proteins for DNA repair. Mechanisms in which BRCT domains regulate DNA repair have yet to be fully elucidated. Studying protein-protein interactions mediated by these domains can improve our understanding of how BRCT domains function in DNA repair. The goal of this dissertation is to characterize the scaffolding functions of BRCT domains and how their interactions contribute to DNA damage repair pathways dysregulated in cancer.
BRCA1, the protein in which the BRCT domain was first identified, is the most well-known cancer susceptibility gene, often mutated in cases of breast and ovarian cancers. Our research has identified that BRCA1 BRCT domain-mediated interactions with the mTORC2 complex disrupt the complex and impair Akt activation, which is critical for cancer cell growth, proliferation, and survival. We have sought to identify how mTORC2 activity may regulate BRCA1 function as a DNA damage regulator and a transcriptional co-activator and contribute to the DNA damage response. We have found that rapamycin treatment increases BRCA1 transcriptional coactivation activity. Also, mTORC2 activity prevents cisplatin-induced cell death. Repression of mTOR signaling reduces gH2AX-BRCA1 foci formation. More importantly, this dissertation work highlights a novel chemotherapeutic strategy of targeting the mTOR pathway for breast cancers with BRCA1 mutations or loss of BRCA1 function. BRCA1 loss sensitizes breast cancer cells to mTOR inhibition. Since the PI3K-mTOR-Akt pathway is upregulated in over 70% of breast cancer cases, breast cancer patients with defective BRCA1 may be ideal candidates for mTOR inhibitor therapeutics.
While BRCT domains are largely associated with DNA repair proteins, there are some BRCT domain-containing proteins for which their DNA repair roles are not fully characterized, such as RNA Polymerase II Subunit A C-Terminal Domain Phosphatase 1 (CTDP1). Our research has revealed CTDP1 as a regulator of FANCI in the Fanconi anemia pathway, a pathway important for the repair of interstrand crosslinks (ICLs). CTDP1 influences FANCI chromatin localization, FANDC2 foci formation, sensitivity to ICL-inducing drugs, and homologous recombination repair. In addition, CTDP1 has also been found to be highly expressed in breast cancer cell lines. CTDP1 knockdown in murine mammary orthotopic models prevents tumor formation, thus rendering CTDP1 as a potential target for breast cancer therapeutics.
The findings in this dissertation work contribute to our overall understanding of how BRCT domains use their scaffolding function to regulate the DNA damage response. Elucidating the biological importance of these domains can improve our understanding of cancer susceptibilities, tailor chemotherapeutic strategies, and make better informed decisions in cancer therapies
A new code for Fourier-Legendre analysis of large datasets: first results and a comparison with ring-diagram analysis
Fourier-Legendre decomposition (FLD) of solar Doppler imaging data is a
promising method to estimate the sub-surface solar meridional flow. FLD is
sensible to low-degree oscillation modes and thus has the potential to probe
the deep meridional flow. We present a newly developed code to be used for
large scale FLD analysis of helioseismic data as provided by the Global
Oscillation Network Group (GONG), the Michelson Doppler Imager (MDI)
instrument, and the upcoming Helioseismic and Magnetic Imager (HMI) instrument.
First results obtained with the new code are qualitatively comparable to those
obtained from ring-diagram analyis of the same time series.Comment: 4 pages, 2 figures, 4th HELAS International Conference "Seismological
Challenges for Stellar Structure", 1-5 February 2010, Arrecife, Lanzarote
(Canary Islands
Impact of Daily Arctic Sea Ice Variability in CAM3.0 during Fall and Winter
Climate projections suggest that an ice-free summer Arctic Ocean is possible within several decades and with this comes the prospect of increased ship traffic and safety concerns. The daily sea ice concentration tendency in five Coupled Model Intercomparison Project phase 5 (CMIP5) simulations is compared with observations to reveal that many models underestimate this quantity that describes high-frequency ice movements, particularly in the marginal ice zone. To investigate whether high-frequency ice variability impacts the atmosphere, the Community Atmosphere Model, version 3.0 (CAM3.0), is forced by sea ice with and without daily fluctuations. Two 100-member ensemble experiments with daily varying (DAILY) and smoothly varying (SMTH) sea ice are conducted, along with a climatological control, for an anoma- lously low ice period (August 2006–November 2007). Results are presented for three periods: September 2006, October 2006, and December–February (DJF) 2006/07. The atmospheric response differs between DAILY and SMTH. In September, sea ice differences lead to an anomalous high and weaker storm activity over northern Europe. During October, the ice expands equatorward faster in DAILY than SMTH in the Siberian seas and leads to a local response of near-surface cooling. In DJF, there is a 1.5-hPa positive sea level pressure anomaly over North America, leading to anomalous northerly flow and anomalously cool continental U.S. temperatures. While the atmospheric responses are modest, the differences arising from high temporal frequency ice variability cannot be ignored. Increasing the accuracy of coupled model sea ice variations on short time scales is needed to improve short-term coupled model forecasts
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