Pile Design Procedure for Stabilizing Channel Slopes

A case history is presented for slope stabilization of channels using piles. The Kansas City District, Corps of Engineers has used various pile designs and types of piles for projects along the Blue River Channel in Kansas City Missouri to stabilize sections of unstable channel slopes in previous slide areas, since June of 1986. Low existing soil shear strengths and limited rights-of-way precluded use of more conventional stabilizing methods. Although a pile analysis method had been used for initial projects, with several piles instrumented with slope indicator devices, an improved analysis method was needed. In July of 1994, through a design analysis, the Kansas City District, Corps of Engineers developed a pile design procedure for the stabilization of a failed slope, along the Blue River Channel, known as the Gregory Blvd Project. The method utilizes both Limit Equilibrium slope stability methods and P-Y curve methods for pile analysis, and takes into account earth pressure theory. The method includes a trial and error procedure for determining the driving forces from a sliding mass of soil. The driving forces were then calculated at a concentrated point on the slide plane, coincident with the location of the piles, or where the piles intersect the slide surface, using limit equilibrium procedures with the most critical slide surface and at the desired factor of safety for the stabilized slope. For projects discussed, shear strengths, were determined from a back analysis of the existing slopes at failure using F=1.0. Laboratory test results generally did not yield usable values. The slope stability computer programs UTEXAS2 and UTEXAS3, using Spencer\u27s Procedure was used in all analyses. The driving forces, thus determined, are then input into the pile analysis (LPILE) program, using both a triangular and a uniform load distribution along with the appropriate soil strength parameters for generating the P-Y curves within the program. Depth of pile embedment below the slip surface, size of the piles, position of the piles in the slope and the required spacing are then determined. Actual instrumented field data located on piles are presented as well as comparisons with predicted results, using the pile procedure analysis technique. The case studies demonstrate the importance of proper formulation of the analysis and of modeling the soil using the correct P-Y soil parameters for the pile

Neonatal Maternal Deprivation Response and Developmental Changes in Gene Expression Revealed by Hypothalamic Gene Expression Profiling in Mice

Neonatal feeding problems are observed in several genetic diseases including Prader-Willi syndrome (PWS). Later in life, individuals with PWS develop hyperphagia and obesity due to lack of appetite control. We hypothesized that failure to thrive in infancy and later-onset hyperphagia are related and could be due to a defect in the hypothalamus. In this study, we performed gene expression microarray analysis of the hypothalamic response to maternal deprivation in neonatal wild-type and Snord116del mice, a mouse model for PWS in which a cluster of imprinted C/D box snoRNAs is deleted. The neonatal starvation response in both strains was dramatically different from that reported in adult rodents. Genes that are affected by adult starvation showed no expression change in the hypothalamus of 5 day-old pups after 6 hours of maternal deprivation. Unlike in adult rodents, expression levels of Nanos2 and Pdk4 were increased, and those of Pgpep1, Ndp, Brms1l, Mett10d, and Snx1 were decreased after neonatal deprivation. In addition, we compared hypothalamic gene expression profiles at postnatal days 5 and 13 and observed significant developmental changes. Notably, the gene expression profiles of Snord116del deletion mice and wild-type littermates were very similar at all time points and conditions, arguing against a role of Snord116 in feeding regulation in the neonatal period

Accelerating the reconstruction of genome-scale metabolic networks

BACKGROUND: The genomic information of a species allows for the genome-scale reconstruction of its metabolic capacity. Such a metabolic reconstruction gives support to metabolic engineering, but also to integrative bioinformatics and visualization. Sequence-based automatic reconstructions require extensive manual curation, which can be very time-consuming. Therefore, we present a method to accelerate the time-consuming process of network reconstruction for a query species. The method exploits the availability of well-curated metabolic networks and uses high-resolution predictions of gene equivalency between species, allowing the transfer of gene-reaction associations from curated networks. RESULTS: We have evaluated the method using Lactococcus lactis IL1403, for which a genome-scale metabolic network was published recently. We recovered most of the gene-reaction associations (i.e. 74 – 85%) which are incorporated in the published network. Moreover, we predicted over 200 additional genes to be associated to reactions, including genes with unknown function, genes for transporters and genes with specific metabolic reactions, which are good candidates for an extension to the previously published network. In a comparison of our developed method with the well-established approach Pathologic, we predicted 186 additional genes to be associated to reactions. We also predicted a relatively high number of complete conserved protein complexes, which are derived from curated metabolic networks, illustrating the potential predictive power of our method for protein complexes. CONCLUSION: We show that our methodology can be applied to accelerate the reconstruction of genome-scale metabolic networks by taking optimal advantage of existing, manually curated networks. As orthology detection is the first step in the method, only the translated open reading frames (ORFs) of a newly sequenced genome are necessary to reconstruct a metabolic network. When more manually curated metabolic networks will become available in the near future, the usefulness of our method in network prediction is likely to increase

Behind the Mirror: Chirality Tunes the Reactivity and Cytotoxicity of Chloropiperidines as Potential Anticancer Agents

The pressing demand for sustainable antitumor drugs prompted us to investigate 3-chloropiperidines as potential mustard-based anticancer agents. In this study, an explorative set of variously decorated monofunctional 3-chloropiperidines (M-CePs) was efficiently synthesized through a fast and affordable route providing high yields of pure racemates and enantiomers. Consistently with their reactivity, M-CePs were demonstrated to alkylate DNA in vitro. On a panel of carcinoma cell lines, M-CePs exhibited low nanomolar cytotoxicity indexes, which showed their remarkable activity against pancreatic cancer cells and in all cases performed strikingly better than the chlorambucil control. Very interestingly, stereochemistry modulated the activity of M-CePs in unexpected ways, pointing to additional molecular mechanisms of action beyond the direct damage of genomic DNA. This encouraging combination of efficacy and sustainability suggests they are valid candidates for anticancer agent development

The sncRNA Zoo: a repository for circulating small noncoding RNAs in animals

The repertoire of small noncoding RNAs (sncRNAs), particularly miRNAs, in animals is considered to be evolutionarily conserved. Studies on sncRNAs are often largely based on homology-based information, relying on genomic sequence similarity and excluding actual expression data. To obtain information on sncRNA expression (including miRNAs, snoRNAs, YRNAs and tRNAs), we performed low-input-volume next-generation sequencing of 500 pg of RNA from 21 animals at two German zoological gardens. Notably, none of the species under investigation were previously annotated in any miRNA reference database. Sequencing was performed on blood cells as they are amongst the most accessible, stable and abundant sources of the different sncRNA classes. We evaluated and compared the composition and nature of sncRNAs across the different species by computational approaches. While the distribution of sncRNAs in the different RNA classes varied significantly, general evolutionary patterns were maintained. In particular, miRNA sequences and expression were found to be even more conserved than previously assumed. To make the results available for other researchers, all data, including expression profiles at the species and family levels, and different tools for viewing, filtering and searching the data are freely available in the online resource ASRA (Animal sncRNA Atlas) at https://www.ccb.uni-saarland.de/asra/

Are There Differences in the Prevalence of Palliative Care-Related Problems in People Living With Advanced Cancer and Eight Non-Cancer Conditions? A Systematic Review

AbstractContextIf access to effective palliative care is to extend beyond cancer patients, an understanding of the comparative prevalence of palliative care problems among cancer and non-cancer patients is necessary.ObjectivesThis systematic review aimed to describe and compare the prevalence of seventeen palliative care-related problems across the four palliative care domains among adults with advanced cancer, acquired immune deficiency syndrome, chronic heart failure, end-stage renal disease (ESRD), chronic obstructive pulmonary disease, multiple sclerosis, motor neuron disease, Parkinson's disease, and dementia.MethodsThree databases were searched using three groups of keywords. The results of the extraction of the prevalence figures were summarized.ResultsThe electronic searches yielded 4697 hits after the removal of 1784 duplicates. Of these hits, 143 met the review criteria. The greatest number of studies were found for advanced cancer (n=57) and ESRD patients (n=47), and 75 of the 143 studies used validated scales. Few data were available for people living with multiple sclerosis (n=2) and motor neuron disease (n=3). The problems with a prevalence of 50% or more found across most of the nine studied diagnostic groups were: pain, fatigue, anorexia, dyspnea, and worry.ConclusionThere are commonalities in the prevalence of problems across cancer and non-cancer patients, highlighting the need for palliative care to be provided irrespective of diagnosis. The methodological heterogeneity across the studies and the lack of non-cancer studies need to be addressed in future research

Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model—a study based on data from an international multicentre project (EPCRC-CSA)

A cancer cachexia classification into stages is warranted in order to guide treatment decisions and clinical trial inclusion. Weight loss and BMI clearly discriminate between non-cachectic and cachectic patients both with regards to all the domains (Intake, Catabolism and Function) and survival. The precachexia stage might be better defined by additional factors in order to be discriminativ

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

A worldwide survey on incidence, management, and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: the POTTER-AF study

AIMS Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management, and outcome are sparse. METHODS AND RESULTS This international multicentre registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553 729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed, at 214 centres in 35 countries. In 78 centres 138 patients [0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (P < 0.0001)] were diagnosed with an oesophageal fistula. Peri-procedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8% and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) [odds ratio 7.463 (2.414, 23.072) P < 0.001]. CONCLUSION Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high