Characteristics of near-fault earthquakes (NFE) are particularly different from that of the far-field ones. Far-field ground motions are characterized by low peak ground acceleration (PGA) and high frequency, whereas near-fault ground motions have a high peak ground velocity (PGV) and long period pulse. Several recent earthquakes, e.g. 1992 Landers, 1994 Northridge, 1995 Kobe, and 1999 Chichi earthquake events, have caused substantial damage to near-fault flexible structures. The nonlinear dynamic behaviour of tall reinforced concrete (RC) frame structures subjected to NFE records is influenced by the characteristics of the foundation soil. The assumption of a fixed-base model for this type of structure might not adequately represent their seismic response. Therefore, the seismic performance evaluation analysis should take into account the soil-structure interaction (SSI). In this study, the seismic performance of a 20-storey and a 6-storey RC frame structures with fixed-base and flexible-base conditions is evaluated. The characteristics of the flexible-base models cover four types of soils, namely, soft soil, medium soil, stiff soil and a rock soil, as classified by the International Building Code. A set of 13 near-fault acceleration time histories recorded on the four types of soil from major earthquake events is selected for the analysis. Three criteria for scaling the records were considered, namely, same maximum spectral acceleration, same spectral acceleration at fundamental period of fixed-base model, and same spectral acceleration at fundamental period of flexible-base model. The analysis evaluates the effect of SSI on the dynamic behaviour by comparing the response of the flexible-base model to the fixed-base model of the structure when subjected to different earthquake records on a specific soil type. It is concluded that SSI effects could vary significantly according to the characteristics of the NFE record, the scaling criterion and the seismic performance indicator representing the SSI. This observation is valid for tall and low-rise structures. 13 near-fault acceleration time histories recorded on the four types of soil from major earthquake events is selected for the analysis. Three criteria for scaling the records were considered, namely, same maximum spectral acceleration, same spectral acceleration at fundamental period of fixed-base model, and same spectral acceleration at fundamental period of flexible-base model. The analysis evaluates the effect of SSI on the dynamic behaviour by comparing the response of the flexible-base model to the fixed-base model of the structure when subjected to different earthquakes records on a specific soil type. DESIGN CONSIDERATION OF THE REINFORCED CONCRETE BUILDINGSTwo RC moment-resisting frame (MRF) buildings are used in this study; a 20-storey building to represent tall structures and a 6-storey building to represent low-rise structures. The structures were designed according to the National Building Code of Canada (NBCC, 1995) and CSA (1994) using 542 K. G...

ANT1, TWINKLE and POLG genes affect mtDNA stability and are involved in autosomal dominant PEO, while mutations in POLG are responsible for numerous clinical presentations, including autosomal recessive PEO, sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO), spino-cerebellar ataxia and epilepsy (SCAE) or Alpers syndrome. In this study, we report on the mutational analysis of ANT1, TWINKLE and POLG genes in 15 unrelated patients, using a dHPLC-based protocol. This series of patients illustrates the large array of clinical presentations associated with mtDNA stability defects, ranging from isolated benign PEO to fatal Alpers syndrome. A total of seven different mutations were identified in six of 15 patients (40%). Six different recessive mutations were found in POLG, one in TWINKLE while no mutation was identified in ANT1. Among the POLG mutations, three are novel and include two missense and one frameshift changes. Seventeen neutral changes and polymorphisms were also identified, including four novel neutral polymorphisms. Overall, this study illustrates the variability of phenotypes associated with mtDNA stability defects, increases the mutational spectrum of POLG variants and provides an efficient and reliable detection protocol for ANT1, TWINKLE and POLG mutational screening.

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Insulin inhibits forkhead O class (FoxO) transcription factors, which down-regulate the expression of genes involved in metabolism, cell cycle arrest, and apoptosis. After being phosphorylated by protein kinase B (PKB) on S253 in its DNA-binding domain, Foxo1 is phosphorylated on T24 and additional sites, which overall triggers its nuclear exclusion. During this process, Foxo1 is thought to retain some transcriptional activity and signaling potential. To evaluate this Foxo1 action, we used a Foxo1-ADA mutant that is constitutively nuclear due to mutation of T24 and S316 to A and harbors a mutation of S253 to D. Adenoviral-mediated expression of Foxo1-ADA in hepatocytes activates PKB and MAPK pathways more than expression of wild-type or of a transactivation domain-deleted mutant (Delta256). PKB activation cannot be accounted for by a Foxo1-mediated increase in upstream signaling components such as insulin receptor substrate 1 or 2 or by Foxo1-mediated down-regulation of Tribbles homolog 3. In contrast, Foxo1-ADA increases p38 activity, and p38 is required for effects of Foxo1 on PKB, at least in part. We propose that Foxo1 turns on a feed-forward loop, relayed by p38 and acting to amplify both PKB activation and Foxo1 inhibition. To conclude, key signaling pathways are activated in hepatocytes through nuclear Foxo1.

Soil analysis for small-scale farms in developing countries is often inconvenient and prohibitively expensive using currently available procedures, yet the information gained from these soil tests could result in economical and environmental benefits. The pressurized hot water (PHW) extraction coupled with colorimetric or turbidimetric analysis shows promise as a viable alternative based on tests done on a limited range of soils. Before this extraction and analysis can be used in developing countries, testing is needed across the range of soils found in these countries. At Brigham Young University (BYU), 228 soils from different areas of Guatemala and Morocco were analyzed for NO 3 -N, phosphorus (P), and potassium (K) using standard methods (water -CTA, Olsen -molybdic acid, and ammonium acetateatomic absorption, respectively). Results were correlated to values obtained from the PHW extraction coupled with colorimetric or turbidimetric analytical procedures. The relationships between the values for these tests were good (r 2 of 0.96, 0.71, and 0.52 for NO 3 -N, P, and K, respectively). Soils from each country were concurrently analyzed for NO 3 -N and P in laboratories in Guatemala and Morocco, and these results were correlated with those from BYU. Positive correlations between BYU values and those from other laboratories were obtained, with the data from the 993 Guatemalan laboratory showing overall closer correlation than the Moroccan laboratory. In an additional study comparing several P extraction methods for Guatemalan soils, relationships between PHW-extracted P and Olsen-, Bray I-, and Mehlich I-extracted P and measured at BYU (r 2 of 0.75, 0.67, and 0.46, respectively) indicate that PHW is a promising alternative P extraction for use even with the highly variable soils of Guatemala. Overall, the data support PHW extraction and accompanying analyses as a less expensive alternative to current soil nutrient extraction and analysis procedures for the soils of Morocco and Guatemala.

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Aims/hypothesis A high-fat diet and obesity are associated with increased risk of liver cancer. Because increased delivery of NEFA to the liver occurs in these conditions, we investigated the involvement of the unsaturated fatty acid oleate in hepatocarcinoma cell proliferation using humanderived hepatocarcinoma cell lines as model systems. Methods Western blotting, FACS analysis and [ 3 H]thymidine incorporation were used to study the signalling pathways and the proliferation of cells cultured for up to 72 h with or without a concentration of oleate considered to be relevant to human pathophysiology (50 μmol/l) or a concentration considered elevated (1 mmol/l). Results In HepG2 cells, proliferation was increased in the presence of 50 μmol/l oleate, but was decreased at 1 mmol/ l. This differential effect was correlated with the activation of the mammalian target of rapamycin complex 1 (mTORC1) and with increased translation of cell cycle regulators. Oleate-mediated mTORC1 activation required phospholipase D activation, which produces phosphatidic acid and is known to render mTORC1 rapamycin resistant.Remarkably, rapamycin resistance was found to affect specifically the mTORC1/eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) branch of the mTORC1 pathway in the presence of 50 μmol/l oleate. Furthermore, inhibition of phosphatidic acid production abolished oleateinduced increases in mTORC1 activity and cyclin A production. Importantly, the same differential effects of oleate on mTORC1 activation, cell cycle regulators and rapamycin resistance were found in SK-Hep1 cells. Conclusions/interpretation Oleate stimulates mTORC1 activation and rapamycin resistance. We propose that rapamycin-derived mTOR inhibitors are likely to be of limited therapeutic use to restrain hepatic tumour growth, particularly in the context of associated obesity.

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