Argonne National Laboratory Report ANL-80-94

The Physics Division's program in nuclear physics covers a broad span of activities within that discipline. The object of this research is to understand the properties of atomic nuclei, their structure and the mechanisms of nuclear reactions. Work is carried out under a variety of subprograis: theory, heavy-ion physics, medium-energy physics and nuclear research

Changes in Hepatic Blood Flow and Liver Function during Closed Abdominal Hyperthermic Intraperitoneal Chemotherapy following Cytoreduction Surgery

Background. The increase in intra-abdominal pressure (IAP) during closed abdominal hyperthermic intraperitoneal chemotherapy (HIPEC) leads to major haemodynamic changes and potential organ dysfunction. We investigated these effects on hepatic blood flow (HBF) and liver function in patients undergoing HIPEC following cytoreductive surgery and fluid management guided by dynamic preload indices. Methods. In this prospective observational clinical study including 15 consecutive patients, we evaluated HBF by transesophageal echocardiography and liver function by determination of the indocyanine green plasma disappearance rate (ICG-PDR). Friedman’s two-way analysis of variance by ranks and Wilcoxon signed-rank test were performed for statistical analysis. Results. During HIPEC, HBF was markedly reduced, resulting in the loss of any pulsatile Doppler flow signal in all but one patient. The ICG-PDR, expressed as median (interquartile 25–75), decreased from 23 (20–30) %/min to 18 (12.5–19) %/min (p<0.001). Despite a generous crystalloid infusion rate (27 (22–35) ml/kg/h), cardiac index decreased during the increased IAP period, inferior vena cava diameter decreased, stroke volume variation and pulse pressure variation increased, lung compliance dropped, and there was an augmentation in plateau pressure. All changes were significant (p<0.001) and reversed to baseline values post HIPEC. Conclusion. Despite optimizing intravenous fluids during closed abdominal HIPEC, we observed a marked decrease in HBF and liver function. Both effects were transient and limited to the period of HIPEC but could influence the choice between closed or open abdominal cavity procedure for HIPEC and should be considered in similar clinical situations of increased IAP

Safe Diagram - A Design And Reliability Tool For Turbine Blading.

LecturePg. 93-102The complex field of turbine blade vibration has long been in need of improved tools to help predict the reliability of blading. The SAFE interference diagram is presented as such a tool. It presents much more information than the widely used Campbell diagram. In evaluating interferences, the SAFE diagram compares not only the frequencies of exciting harmonics with natural frequencies of blades, but also the shape of these harmonics with the normal mode shapes of a completely bladed disc including packeted blading. Examples are given of cases where the Campbell diagram predicts a dangerous resonance while the SAFE diagram shows that no resonances exist which are supported by experience. Examples are also provided to show when the SAFE diagram can pinpoint what interference is likely to cause the largest blade vibration. Finally, it is shown how a simple change in packeting can be used to change the blade interference and to avoid dangerous operation

Structural basis for mutation-induced destabilization of profilin 1 in ALS

Mutations in profilin 1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS); however, the pathological mechanism of PFN1 in this fatal disease is unknown. We demonstrate that ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported loss-of-function phenotypes in cell-based assays. The source of this destabilization is illuminated by the X-ray crystal structures of several PFN1 proteins, revealing an expanded cavity near the protein core of the destabilized M114T variant. In contrast, the E117G mutation only modestly perturbs the structure and stability of PFN1, an observation that reconciles the occurrence of this mutation in the control population. These findings suggest that a destabilized form of PFN1 underlies PFN1-mediated ALS pathogenesis

Pulmonary Arterial Hypertension Related to HIV Infection: Improved Hemodynamics and Survival Associated with Antiretroviral Therapy

This study aimed to assess the long-term course of pulmonary arterial hypertension related to infection with human immunodeficiency virus (PAHRH) and the influence of antiretroviral therapy (ART) on its characteristics. We retrospectively analyzed all 47 patients in the Swiss HIV Cohort Study in whom PAHRH was diagnosed. Among 35 patients who underwent follow-up Doppler echocardiography, the right ventricular systolic pressure over right atrial pressure gradient increased by a median of 25 mm Hg in 9 patients who had not received ART, decreased by a median of 3 mm Hg in 12 patients who had received nucleoside analogs, and decreased by a median of 21 mm Hg in 14 patients who had received highly active ART (HAART) (P < .005). Among all 47 patients, median duration of survival after PAHRH diagnosis was 2.7 years. HAART significantly decreased mortality due to PAHRH as well as other causes. This study suggests a beneficial effect of combination ART in patients with PAHR

Climate stress resistance in male Queensland fruit fly varies among populations of diverse geographic origins and changes during domestication

Background: The highly polyphagous Queensland fruit fly (Bactrocera tryoni Froggatt) expanded its range substantially during the twentieth century and is now the most economically important insect pest of Australian horticulture, prompting intensive efforts to develop a Sterile Insect Technique (SIT) control program. Using a “common garden” approach, we have screened for natural genetic variation in key environmental fitness traits among populations from across the geographic range of this species and monitored changes in those traits induced during domestication. Results: Significant variation was detected between the populations for heat, desiccation and starvation resistance and wing length (as a measure of body size). Desiccation resistance was correlated with both starvation resistance and wing length. Bioassay data for three resampled populations indicate that much of the variation in desiccation resistance reflects persistent, inherited differences among the populations. No latitudinal cline was detected for any of the traits and only weak correlations were found with climatic variables for heat resistance and wing length. All three stress resistance phenotypes and wing length changed significantly in certain populations with ongoing domestication but there was also a strong population by domestication interaction effect for each trait. Conclusions: Ecotypic variation in heat, starvation and desiccation resistance was detected in Australian Qfly populations, and these stress resistances diminished rapidly during domestication. Our results indicate a need to select source populations for SIT strains which have relatively high climatic stress resistance and to minimise loss of that resistance during domestication

Ancient and novel small RNA pathways compensate for the loss of piRNAs in multiple independent nematode lineages.

Small RNA pathways act at the front line of defence against transposable elements across the Eukaryota. In animals, Piwi interacting small RNAs (piRNAs) are a crucial arm of this defence. However, the evolutionary relationships among piRNAs and other small RNA pathways targeting transposable elements are poorly resolved. To address this question we sequenced small RNAs from multiple, diverse nematode species, producing the first phylum-wide analysis of how small RNA pathways evolve. Surprisingly, despite their prominence in Caenorhabditis elegans and closely related nematodes, piRNAs are absent in all other nematode lineages. We found that there are at least two evolutionarily distinct mechanisms that compensate for the absence of piRNAs, both involving RNA-dependent RNA polymerases (RdRPs). Whilst one pathway is unique to nematodes, the second involves Dicer-dependent RNA-directed DNA methylation, hitherto unknown in animals, and bears striking similarity to transposon-control mechanisms in fungi and plants. Our results highlight the rapid, context-dependent evolution of small RNA pathways and suggest piRNAs in animals may have replaced an ancient eukaryotic RNA-dependent RNA polymerase pathway to control transposable elements.We thank Sylviane Moss for high-throughput sequencing support. We thank Charles Bradshaw for help with computation and IT. We thank Marie-Anne Felix and Frank Jiggins for critical comments on the manuscript. We thank Matt Berriman (Wellcome Trust Sanger Centre, Hinxton, Cambridge, UK) for allowing us to use unpublished genomic sequencing data for N. brasiliensis. We thank Einhardt Schierenberg (University of Cologne, Germany) and Werner Armonies (Alfred Wegener Institute, Sylt, Germany) for help with collection of E. brevis.This is the final version of the article, originally published in PLoS Biology, 2015, 13(2): e1002061. doi:10.1371/journal.pbio.100206