A geothermal aquifer in the dilation zones on the southern margin of the Dublin Basin

This is the author accepted manuscript. the final version is available from Oxford University Press via the DOI in this recordWe present modelling of the geophysical data from the Newcastle area, west of Dublin, Ireland within the framework of the IRETHERM project. IRETHERM's overarching objective was to facilitate a more thorough strategic understanding of Ireland's geothermal energy potential through integrated modelling of new and existing geophysical, geochemical and geological data. The Newcastle area, one of the target localities, is situated at the southern margin of the Dublin Basin, close to the largest conurbation on the island of Ireland in the City of Dublin and surrounds. As part of IRETHERM, magnetotelluric (MT) soundings were carried out in the highly urbanized Dublin suburb in 2011 and 2012, and a description of MT data acquisition, processing methods, multi-dimensional geoelectrical models and porosity modelling with other geophysical data are presented. The MT time series were heavily noise-contaminated and distorted due to electromagnetic noise from nearby industry and Dublin City tram/railway systems. Time series processing was performed using several modern robust codes to obtain reasonably reliable and interpretable MT impedance and geomagnetic transfer function ‘tipper’ estimates at most of the survey locations. The most ‘quiet’ 3-hour subsets of data during the night time, when the DC ‘LUAS’ tram system was not operating, were used in multi-site and multivariate processing. The final 2-D models underwent examination using a stability technique, and the final two 2-D profiles, with reliability estimations expressed through conductance and resistivity, were derived. In the final stage of this study, 3-D modelling of all magnetotelluric data in the Newcastle area was also undertaken. Comparison of the MT models and their interpretation with existing seismic profiles in the area reveals that the Blackrock to Newcastle Fault (BNF) zone is visible in the models as a conductive feature down to depths of 4 km. The investigated area below Newcastle can be divided into two domains of different depths, formed as depth zones. The first zone, from the surface down to 1–2 km, is dominated by NE-SW oriented conductors connected with shallow faults or folds probably filled with less saline waters. The conductors are also crossing the surface trace of the BNF. The second depth domain can be identified from depths of 2 km to 4 km, where structures are oriented along the BNF and the observed conductivity is lower. The deeper conductive layers are interpreted as geothermal-fluid-bearing rocks. Porosity and permeability estimations from the lithological borehole logs indicate the geothermal potential of the bedrock, to deliver warm water to the surface. The fluid permeability estimation, based on Archie's law for porous structures and synthetic studies of fractured zones, suggests a permeability in the range 100 mD–100 D in the study area, which is prospective for geothermal energy exploitation.Science Foundation Ireland (SFI)Slovak Academy of Sciences (SAS)European Union FP7APVVSlovak Grant Agency VEG

Formulation of resveratrol into PGA-co-PDL nanoparticles increases its cytotoxic potency against lung cancer cells

Lung cancer is the commonest cause of cancer-related deaths, and current treatment involves the use of cytotoxic drugs which have many unwanted side-effects. Resveratrol, a natural polyphenol, has promising anticancer efficacy, but its therapeutic application is hindered by low bioavailability, which this study sought to improve through encapsulation into nanoparticles (NPs).Resveratrol was loaded into poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL; MWt 16.5 KDa) NPs with sizes between 220-230 nm, and tested against Calu-3 human lung cancer cells. Key findings 5% and 10% resveratrol nanoparticles (RNPs) had a high encapsulation efficiency of 78 ± 0.24% and 70 ± 0.89% and a drug loading of 39 ± 0.12 µg and 70 ± 0.89 µg (w/w), respectively. The PGA-co-PDL blank NP (BNP) at 1 mg/mL had good cytocompatibility when Calu-3 cells were exposed to it for 24 h (cell viability of 87.5±4.7%). Remarkably, the 5% RNP and 10% RNP lowered, up to 80%, the IC50 for 24 h cytotoxicity of resveratrol against the cells, from 158 ± 16 µM to 32 ± 10 µM and 70 ± 13 µM, respectively. Conclusions Loading of resveratrol into PGA-co-PDL NPs increases its anticancer potency, thus enhancing its prospect for treating lung cancer

Delivery of natural phenolic compounds for the potential treatment of lung cancer.

The application of natural products to treat various diseases, such as cancer, has been an important area of research for many years. Several phytochemicals have demonstrated anticarcinogenic activity to prevent or reduce the progression of cancer by modulating various cellular mechanisms. However, poor bioavailability has hindered clinical success and the incorporation of these drugs into efficient drug delivery systems would be beneficial. For lung cancer, local delivery via the pulmonary route would also be more effective. In this article, recent in vitro scientific literature on phenolic compounds with anticancer activity towards lung cancer cell lines is reviewed and nanoparticulate delivery is mentioned as a possible solution to the problem of bioavailability. The first part of the review will explore the different classes of natural phenolic compounds and discuss recent reports on their activity on lung cancer cells. Then, the problem of the poor bioavailability of phenolic compounds will be explored, followed by a summary of recent advances in improving the efficacy of these phenolic compounds using nanoparticulate drug delivery systems. Graphical abstract The rationale for direct delivery of phenolic compounds loaded in microparticles to the lungs

Considering the Case for Biodiversity Cycles: Reexamining the Evidence for Periodicity in the Fossil Record

Medvedev and Melott (2007) have suggested that periodicity in fossil biodiversity may be induced by cosmic rays which vary as the Solar System oscillates normal to the galactic disk. We re-examine the evidence for a 62 million year (Myr) periodicity in biodiversity throughout the Phanerozoic history of animal life reported by Rohde & Mueller (2005), as well as related questions of periodicity in origination and extinction. We find that the signal is robust against variations in methods of analysis, and is based on fluctuations in the Paleozoic and a substantial part of the Mesozoic. Examination of origination and extinction is somewhat ambiguous, with results depending upon procedure. Origination and extinction intensity as defined by RM may be affected by an artifact at 27 Myr in the duration of stratigraphic intervals. Nevertheless, when a procedure free of this artifact is implemented, the 27 Myr periodicity appears in origination, suggesting that the artifact may ultimately be based on a signal in the data. A 62 Myr feature appears in extinction, when this same procedure is used. We conclude that evidence for a periodicity at 62 Myr is robust, and evidence for periodicity at approximately 27 Myr is also present, albeit more ambiguous.Comment: Minor modifications to reflect final published versio

Bim and Bmf synergize to induce apoptosis in Neisseria gonorrhoeae infection

Abstract: Bcl-2 family proteins including the pro-apoptotic BH3-only proteins are central regulators of apoptotic cell death. Here we show by a focused siRNA miniscreen that the synergistic action of the BH3-only proteins Bim and Bmf is required for apoptosis induced by infection with Neisseria gonorrhoeae (Ngo). While Bim and Bmf were associated with the cytoskeleton of healthy cells, they both were released upon Ngo infection. Loss of Bim and Bmf from the cytoskeleton fraction required the activation of Jun-N-terminal kinase-1 (JNK-1), which in turn depended on Rac-1. Depletion and inhibition of Rac-1, JNK-1, Bim, or Bmf prevented the activation of Bak and Bax and the subsequent activation of caspases. Apoptosis could be reconstituted in Bim-depleted and Bmf-depleted cells by additional silencing of antiapoptotic Mcl-1 and Bcl-XL, respectively. Our data indicate a synergistic role for both cytoskeletal-associated BH3-only proteins, Bim, and Bmf, in an apoptotic pathway leading to the clearance of Ngo-infected cells. Author Summary: A variety of physiological death signals, as well as pathological insults, trigger apoptosis, a genetically programmed form of cell death. Pathogens often induce host cell apoptosis to establish a successful infection. Neisseria gonorrhoeae (Ngo), the etiological agent of the sexually transmitted disease gonorrhoea, is a highly adapted obligate human-specific pathogen and has been shown to induce apoptosis in infected cells. Here we unveil the molecular mechanisms leading to apoptosis of infected cells. We show that Ngo-mediated apoptosis requires a special subset of proapoptotic proteins from the group of BH3-only proteins. BH3-only proteins act as stress sensors to translate toxic environmental signals to the initiation of apoptosis. In a siRNA-based miniscreen, we found Bim and Bmf, BH3-only proteins associated with the cytoskeleton, necessary to induce host cell apoptosis upon infection. Bim and Bmf inactivated different inhibitors of apoptosis and thereby induced cell death in response to infection. Our data unveil a novel pathway of infection-induced apoptosis that enhances our understanding of the mechanism by which BH3-only proteins control apoptotic cell death

Risk Factors for Breast Cancer and Expression of Insulin-Like Growth Factor-2 (IGF-2) in Women with Breast Cancer in Wuhan City, China

PURPOSE: The purpose of this study was to explore the risk factors for breast cancer and establish the expression rate of IGF-2 in female patients. METHODS: A case control study with 500 people in case group and 500 people in control group. A self-administered questionnaire was used to investigate risk factors for breast cancer. All cases were interviewed during a household survey. Immune-histochemical method was used to inspect the expression of IGF-2 in different tissues (benign breast lesions, breast cancer and tumor-adjacent tissue). RESULTS: Multivariate adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression. High body mass index (OR = 1.012,95%CI = 1.008-1.016), working attributes (OR = 1.004, 95%CI = 1.002 = 1.006), long menstrual period (OR = 1.007, 95%CI = 1.005-1.009), high parity OR = 1.003, 95%CI = 1.001-1.005) , frequent artificial abortion (OR = 1.004, 95%CI = 1.001-1.005), family history of cancer (OR = 1.003, 95%CI = 1.000-1.005), period of night shift (OR = 1.003, 95%CI = 1.001-1.006), live in high risk environment (OR = 1.005, 95%CI = 1.002-1.008), and family problems (OR = 1.010, 95%CI = 1.005-1.014) were associated with increased risk for breast cancer. In this study, good sleeping status, positive coping strategies, subjective support, and utility degree of social support were associated with reduced risk for breast cancer (OR = 0.998, 0.997, 0.985, 0.998 respectively; 95%CI = 0.996-1.000, 0.994-1.000, 0.980-0.989, 0.996-1.000, respectively). In benign breast lesions, breast cancer and tumor-adjacent tissue, IGF-2 was mainly expressed in the cytoplasm, but its expression rate was different (p<0.05). CONCLUSIONS: The incidence of breast cancer is a common result of multiple factors. IGF-2 is involved in the development of breast cancer, and its expression varies in different tissues (benign breast lesions, breast cancer and tumor-adjacent tissue)

Mechanical Strength of 17 134 Model Proteins and Cysteine Slipknots

A new theoretical survey of proteins' resistance to constant speed stretching is performed for a set of 17 134 proteins as described by a structure-based model. The proteins selected have no gaps in their structure determination and consist of no more than 250 amino acids. Our previous studies have dealt with 7510 proteins of no more than 150 amino acids. The proteins are ranked according to the strength of the resistance. Most of the predicted top-strength proteins have not yet been studied experimentally. Architectures and folds which are likely to yield large forces are identified. New types of potent force clamps are discovered. They involve disulphide bridges and, in particular, cysteine slipknots. An effective energy parameter of the model is estimated by comparing the theoretical data on characteristic forces to the corresponding experimental values combined with an extrapolation of the theoretical data to the experimental pulling speeds. These studies provide guidance for future experiments on single molecule manipulation and should lead to selection of proteins for applications. A new class of proteins, involving cystein slipknots, is identified as one that is expected to lead to the strongest force clamps known. This class is characterized through molecular dynamics simulations.Comment: 40 pages, 13 PostScript figure