Chromatin remodelers in the DNA double strand break response

During my PhD project, I studied the role of several chromatin remodelers in the DNA double strand break (DSB) response. We discovered that both CHD4 and SMARCA5 are required for ubiquitin signaling through the E3 ubiquitin ligases RNF8 and RNF168, which is a central signaling event in the response to DSBs. Furthermore, we found that SMARCA5 actually interacts with RNF168. Both CHD4 and SMARCA5 act at the break site itself and modulate DSB repair. Additionally we found that the DSB repair protein Rad51 is essential for mouse development since Rad51C knock out mice were embryonic lethal.J.E. Jurriaanse Stichting Sectra.UBL - phd migration 2018UBL - phd migration 201

Investigation of an integrated switchgrass gasification/fuel cell power plant. Final report for Phase 1 of the Chariton Valley Biomass Power Project

The Chariton Valley Biomass Power Project, sponsored by the US Department of Energy Biomass Power Program, has the goal of converting switchgrass grown on marginal farmland in southern Iowa into electric power. Two energy conversion options are under evaluation: co-firing switchgrass with coal in an existing utility boiler and gasification of switchgrass for use in a carbonate fuel cell. This paper describes the second option under investigation. The gasification study includes both experimental testing in a pilot-scale gasifier and computer simulation of carbonate fuel cell performance when operated on gas derived from switchgrass. Options for comprehensive system integration between a carbonate fuel cell and the gasification system are being evaluated. Use of waste heat from the carbonate fuel cell to maximize overall integrated plant efficiency is being examined. Existing fuel cell power plant design elements will be used, as appropriate, in the integration of the gasifier and fuel cell power plant to minimize cost complexity and risk. The gasification experiments are being performed by Iowa State University and the fuel cell evaluations are being performed by Energy Research Corporation

Role of p53 Serine 46 in p53 Target Gene Regulation

The tumor suppressor p53 plays a crucial role in cellular growth control inducing a plethora of different response pathways. The molecular mechanisms that discriminate between the distinct p53-responses have remained largely elusive. Here, we have analyzed the p53-regulated pathways induced by Actinomycin D and Etoposide treatment resulting in more growth arrested versus apoptotic cells respectively. We found that the genome-wide p53 DNA-binding patterns are almost identical upon both treatments notwithstanding transcriptional differences that we observed in global transcriptome analysis. To assess the role of post-translational modifications in target gene choice and activation we investigated the genome-wide level of phosphorylation of Serine 46 of p53 bound to DNA (p53-pS46) and of Serine 15 (p53-pS15). Interestingly, the extent of S46 phosphorylation of p53 bound to DNA is considerably higher in cells directed towards apoptosis while the degree of phosphorylation at S15 remains highly similar. Moreover, our data suggest that following different chemotherapeutical treatments, the amount of chromatin-associated p53 phosphorylated at S46 but not at pS15 is higher on certain apoptosis related target genes. Our data provide evidence that cell fate decisions are not made primarily on the level of general p53 DNA-binding and that post-translationally modified p53 can have distinct DNA-binding characteristics

Controlled Assembly of Macromolecular β-Sheet Fibrils

Construction of functional molecular devices by directed assembly processes is one of the main challenges in the field of nanotechnology. Many approaches to this challenge use biological assembly as a source of inspiration for the build up of new materials with controlled organization at the nanoscale. In particular, the self-assembly properties of β-sheet peptides have been used in the design of supramolecular materials, such as tapes, nanotubes, and fibrils

Post-operative critical care management of patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC)

<p>Abstract</p> <p>Background</p> <p>Cytoreductive surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC) results in a number of physiological changes with effects on the cardiovascular system, oxygen consumption and coagulation. The Critical Care interventions required by this cohort of patients have not yet been quantified.</p> <p>Methods</p> <p>This retrospective audit examines the experience of a Specialist Tertiary Centre in England over an 18 month period (January 2009-June 2010) during which 69 patients underwent CRS and HIPEC. All patients were extubated in the operating theatre and transferred to the Critical Care Unit (CCU) for initial post-operative management.</p> <p>Results</p> <p>Patients needed to remain on the CCU for 2.4 days (0.8-7.8). There were no 30 day mortalities. The majority of patients (70.1%) did not require post-operative organ support. 2 patients who developed pneumonia post-operatively required respiratory support. 18 (26.1%) patients required vasopressor support with norepinephrine with a mean duration of 13.94 hours (5-51 hours) and mean dose of 0.04 mcg/kg/min. Post-operative coagulopathy peaked at 24 hours. A significant drop in serum albumin was observed.</p> <p>Conclusion</p> <p>The degree of organ support required post-operatively is minimal. Early extubation is efficacious with the aid of epidural analgesia. Critical Care monitoring for 48 hours is desirable in view of the post-operative challenges.</p

A new instrument to measure high value, cost-conscious care attitudes among healthcare stakeholders: Development of the MHAQ

Background: Residents have to learn to provide high value, cost-conscious care (HVCCC) to counter the trend of excessive healthcare costs. Their learning is impacted by individuals from different stakeholder groups within the workplace environment. These individuals' attitudes toward HVCCC may influence how and what residents learn. This study was carried out to develop an instrument to reliably measure HVCCC attitudes among residents, staff physicians, administrators, and patients. The instrument can be used to assess the residency-training environment. Method: The Maastricht HVCCC Attitude Questionnaire (MHAQ) was developed in four phases. First, we conducted exploratory factor analyses using original data from a previously published survey. Next, we added nine items to strengthen subscales and tested the new questionnaire among the four stakeholder groups. We used exploratory factor analysis and Cronbach's alphas to define subscales, after which the final version of the MHAQ was constructed. Finally, we used generalizability theory to determine the number of respondents (residents or staff physicians) needed to reliably measure a specialty attitude score. Results: Initial factor analysis identified three subscales. Thereafter, 301 residents, 297 staff physicians, 53 administrators and 792 patients completed the new questionnaire between June 2017 and July 2018. The best fitting subscale composition was a three-factor model. Subscales were defined as high-value care, cost incorporation, and perceived drawbacks. Cronbach's alphas were between 0.61 and 0.82 for all stakeholders on all subscales. Sufficient reliability for assessing national specialty attitude (G-coefficient > 0.6) could be achieved from 14 respondents. Conclusions: The MHAQ reliably measures individual attitudes toward HVCCC in different stakeholders in health care contexts. It addresses key dimensions of HVCCC, providing content validity evidence. The MHAQ can be used to identify frontrunners of HVCCC, pinpoint aspects of residency training that need improvement, and benchmark and compare across specialties, hospitals and regions

Reconstruction and subsurface lattice distortions in the (2 × 1)O-Ni(110) structure: A LEED analysis

LEED analysis of the reconstructed (2 × 1)O-Ni(110) system clearly favors the “missing row” structure over the “saw-tooth” and “buckled row” models. By using a novel computational procedure 8 structural parameters could be refined simultaneously, leading to excellent R-factors (RZJ = 0.09, RP = 0.18). The adsorbed O atoms are located 0.2 Å above the long bridge sites in [001] direction, presumably with a slight displacement ( 0.1 Å) in [1 0] direction to an asymmetric adsorption site. The nearest-neighbor Ni---O bond lengths (1.77 Å) are rather short. The separation between the topmost two Ni layers is expanded to 1.30 Å (bulk value 1.25 Å), while that between the second and third layer is slightly contracted to 1.23 Å. The third layer is, in addition, slightly buckled (±0.05 Å). The results are discussed on the basis of our present general knowledge about the structure of adsorbate covered metallic surfaces

Managing soil carbon and nitrogen for productivity and environmental quality

Includes bibliographical references (pages 774-775).In this study, we investigated the impact of cropping system management on C and N pools, crop yield, and N leaching in a long-term agronomic experiment in Southwest Michigan. Four management types, conventional (CO), integrated fertilizer (IF), integrated compost (IC), and transitional organic (TO) were applied to two crop sequences, a corn (Zea mays L.)–corn–soybean [Glycine max (L.) Merr.]–wheat (Triticum aestivum L.) rotation and continuous corn, which were grown with and without cover crops in the IF, IC, and TO managements. Using compost as a fertility source and reducing the use of herbicides and other chemicals resulted in long-term changes in soil organic matter pools such TO ≥ IC > IF ≥ CO for total C and N and for the labile C and N measured through aerobic incubations at 70 and 150 d. Mineralizable N varied within the rotation, tending to increase after soybean and decrease after corn production in all systems. Corn yield was closely associated with 70-d N mineralization potential, being greatest for first-year corn with cover and least for continuous corn without cover under all management types. Although the TO and IC systems produced the lowest yield for second-year or continuous corn, the combination of soybean and wheat plus red clover (Trifolium pratense L.) always supported high yield for first-year corn. Fall nitrate level and nitrate leaching were higher for commercially fertilized corn than for any other crop or for compost-amended corn