South Channel Dam Rehabilitation Project - Successfully Addressing Dam Rehabilitation Challenges

The Post Falls South Channel Dam is located on the Spokane River in Post Falls, Idaho. The concrete gravity dam was constructed in 1906 and was recently rehabilitated. The rehabilitation project included several design elements; the primary objectives were the replacement of the six spillway gates and hoists and significant rehabilitation of the concrete. The South Channel Dam rehabilitation encountered several challenges due to the age and condition of the existing structure, the large scale of the rehabilitation, and the location of the project. The concrete rehabilitation addressed several challenges which are presented in detail. The existing concrete consisted of cyclopean concrete; concrete demolition and surface preparation also revealed large voids and substantial areas of low strength material. This paper presents lessons learned along with procedural methods implemented for effective change management during construction. The project was ultimately a success in a large part due to the team approach and practices implemented during construction

Stoics against stoics in Cudworth's "A Treatise of Freewill"

In his 'A Treatise of Freewill', Ralph Cudworth argues against Stoic determinism by drawing on what he takes to be other concepts found in Stoicism, notably the claim that some things are ‘up to us’ and that these things are the product of our choice. These concepts are central to the late Stoic Epictetus and it appears at first glance as if Cudworth is opposing late Stoic voluntarism against early Stoic determinism. This paper argues that in fact, despite his claim to be drawing on Stoic doctrine, Cudworth uses these terms with a meaning first articulated only later, by the Peripatetic commentator Alexander of Aphrodisias

Quantitative trait loci mapping reveals candidate pathways regulating cell cycle duration in Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Elevated parasite biomass in the human red blood cells can lead to increased malaria morbidity. The genes and mechanisms regulating growth and development of <it>Plasmodium </it><it>falciparum </it>through its erythrocytic cycle are not well understood. We previously showed that strains HB3 and Dd2 diverge in their proliferation rates, and here use quantitative trait loci mapping in 34 progeny from a cross between these parent clones along with integrative bioinformatics to identify genetic loci and candidate genes that control divergences in cell cycle duration.</p> <p>Results</p> <p>Genetic mapping of cell cycle duration revealed a four-locus genetic model, including a major genetic effect on chromosome 12, which accounts for 75% of the inherited phenotype variation. These QTL span 165 genes, the majority of which have no predicted function based on homology. We present a method to systematically prioritize candidate genes using the extensive sequence and transcriptional information available for the parent lines. Putative functions were assigned to the prioritized genes based on protein interaction networks and expression eQTL from our earlier study. DNA metabolism or antigenic variation functional categories were enriched among our prioritized candidate genes. Genes were then analyzed to determine if they interact with cyclins or other proteins known to be involved in the regulation of cell cycle.</p> <p>Conclusions</p> <p>We show that the divergent proliferation rate between a drug resistant and drug sensitive parent clone is under genetic regulation and is segregating as a complex trait in 34 progeny. We map a major locus along with additional secondary effects, and use the wealth of genome data to identify key candidate genes. Of particular interest are a nucleosome assembly protein (PFL0185c), a Zinc finger transcription factor (PFL0465c) both on chromosome 12 and a ribosomal protein L7Ae-related on chromosome 4 (PFD0960c).</p

Protocols and characterization data for 2D, 3D, and slice-based tumor models from the PREDECT project

Two-dimensional (2D) culture of cancer cells in vitro does not recapitulate the three-dimensional (3D) architecture, heterogeneity and complexity of human tumors. More representative models are required that better reflect key aspects of tumor biology. These are essential studies of cancer biology and immunology as well as for target validation and drug discovery. The Innovative Medicines Initiative (IMI) consortium PREDECT (www.predect.eu) characterized in vitro models of three solid tumor types with the goal to capture elements of tumor complexity and heterogeneity. 2D culture and 3D mono-and stromal cocultures of increasing complexity, and precision-cut tumor slice models were established. Robust protocols for the generation of these platforms are described. Tissue microarrays were prepared from all the models, permitting immunohistochemical analysis of individual cells, capturing heterogeneity. 3D cultures were also characterized using image analysis. Detailed step-by-step protocols, exemplary datasets from the 2D, 3D, and slice models, and refined analytical methods were established and are presented.Peer reviewe

Adjuvant radiotherapy for primary breast cancer in BRCA1 and BRCA2 mutation carriers and risk of contralateral breast cancer with special attention to patients irradiated at younger age

The purpose of this study was to estimate the influence of adjuvant radiotherapy for primary breast cancer (BC) on the risk of contralateral BC (CBC) in BRCA1 or BRCA2(BRCA1/2) mutation carriers, with special attention to patients irradiated at age younger than 40 years. Additionally, tendencies in locoregional treatments and rates of contralateral risk-reducing mastectomy over time were explored. In this retrospective cohort study, 691 BRCA1/2-associated BC patients treated between 1980 and 2013 were followed from diagnosis until CBC or censoring event including ipsilateral BC recurrence, distant metastasis, contralateral risk-reducing mastectomy, other invasive cancer diagnosis, death, or loss to follow up. Hazard ratios (HR) for CBC associated with radiotherapy were estimated using Cox regression. Median follow-up time was 8.6 years [range 0.3–34.3 years]. No association between radiotherapy for primary BC and risk of CBC was found, neither in the total population (HR 0.82, 95 % CI 0.45–1.49) nor in the subgroup of patients younger than 40 years at primary diagnosis (HR 1.36, 95 % CI 0.60–3.09). During follow-up, the number of patients at risk decreased substantially since a large proportion of patients were censored after contralateral risk-reducing mastectomy or BC recurrence. Over the years, increasing preference for mastectomy without radiotherapy compared to breast-conserving surgery with radiotherapy was found ranging from less than 30 % in 1995 to almost 50 % after 2010. The rate of contralateral risk-reducing mastectomy increased over the years from less than 40 % in 1995 to more than 60 % after 2010. In this cohort of BRCA1/2-associated BC patients, no association between radiotherapy for primary BC and risk of CBC was observed in the total group, nor in the patients irradiated before the age of 40 years. The number of patients at risk after 10 and 15 years of follow-up, however, was too small to definitively exclude harmful effects of adjuvant radiotherapy

Physio-chemical characterization of three-component co-amorphous systems generated by a melt-quench method

The purpose of this work was to evaluate the possibility of creating a ternary co-amorphous system and to determine how the properties of a co-amorphous material are altered by the addition of a selected third component. Piroxicam and indomethacin form a stable co-amorphous with the Tg above room temperature. The third component added was selected based on tendency to crystallise (benzamide, caffeine) or form amorphous (acetaminophen, clotrimazole) on cooling. Generated co-amorphous systems were characterised with TGA, HSM, DSC, FTIR, and XRD. Stable ternary co-amorphous systems were successfully generated, which was confirmed using XRD, DSC and FTIR analysis. In all cases, Tg of the ternary system was lower than the Tg of the binary system, although higher than that of the individual third compound. Upon storage for 4 weeks all created ternary systems showed significantly smaller variation in Tg compared to the binary system. Stable three-component co-amorphous systems can be generated via melt quench method using either a crystalline or amorphous third component. Addition of third component can alter the Tg of co-amorphous system and in all cases created more stable co-amorphous system upon storage. Physical parameters may not be sufficient in predicting the resulting Tg, therefore knowledge of chemical interaction must be brought into equation as well