Comparative analysis of 8-oxo-2' -deoxyguanosine in DNA by 32P- and 33P-postlabeling and electrochemical detection

8-Oxo-2'-deoxyguanosine (8-oxo-dG) is emerging as a useful marker for oxidative DNA damage. Reported basal levels determined by 32P-postlabeling (PPL) method were 10-fold or more higher than those obtained with HPLC/electrochemical detection (ECD). This discrepancy was investigated. In commercial calf thymus DNA, levels of 4 +/- 1 and 64 +/- 14 8-oxo-dG per 10(6) 2'-deoxynucleosides (dN) were measured by the standard HPLC/ECD and PPL methods, respectively. DNA digestion by micrococcal nuclease/spleen phosphodiesterase and nuclease P1 (as used in the standard PPL method), followed by ECD analysis resulted in a level of 8 +/- 3. In calf thymus DNA spiked with chemically synthesized 8-oxo-dGp to give an increment of 9 8-oxo-dG/10(6) dN, the added standard produced a significant increase with HPLC/ECD but not PPL. After spiking the DNA with 90 8-oxo-dG/10(6) dN, the added 8-oxo-dGp was detectable also with PPL, with a labeling efficiency of 65%. In order to investigate the role of ionizing radiation from 32P for the higher 8-oxo-dG levels in PPL, incubation times and amounts of radioactivity in the phosphorylation reaction with commercial dGp were increased, and external irradiation of commercial dG with 32P was investigated. All modifications resulted in higher values of 8-oxo-dG measured, but the effect was not large enough to fully explain the discrepancy between PPL and HPLC/ECD. Using [gamma-33P]ATP instead of [gamma-32P]ATP or adding [33P]phosphate to a 32P-PPL assay resulted in even higher levels of 8-oxo-dG measured. The increase in 8-oxo-dG levels during the PPL workup is attributed to the presence and oxidation of unmodified dGp in the reaction mixture. For a determination of true basal levels, the PPL method will have to be modified, including the removal of dGp prior to the phosphorylation reaction.     

Reference publication year spectroscopy (RPYS) of Eugene Garfield’s publications

Which studies, theories, and ideas have influenced Eugene Garfield’s scientific work? Recently, the method reference publication year spectroscopy (RPYS) has been introduced, which can be used to answer this and related questions. Since then, several studies have been published dealing with the historical roots of research fields and scientists. The program CRExplorer (http://www.crexplorer.net) was specifically developed for RPYS. In this study, we use this program to investigate the historical roots of Eugene Garfield’s oeuvre.     

JavAdaptor—Flexible runtime updates of Java applications

Software is changed frequently during its life cycle. New requirements come, and bugs must be fixed. To update an application, it usually must be stopped, patched, and restarted. This causes time periods of unavailability, which is always a problem for highly available applications. Even for the development of complex applications, restarts to test new program parts can be time consuming and annoying. Thus, we aim at dynamic software updates to update programs at runtime. There is a large body of research on dynamic software updates, but so far, existing approaches have shortcomings either in terms of flexibility or performance. In addition, some of them depend on specific runtime environments and dictate the program's architecture. We present JavAdaptor , the first runtime update approach based on Java that (a) offers flexible dynamic software updates, (b) is platform independent, (c) introduces only minimal performance overhead, and (d) does not dictate the program architecture. JavAdaptor combines schema changing class replacements by class renaming and caller updates with Java HotSwap using containers and proxies. It runs on top of all major standard Java virtual machines. We evaluate our approach's applicability and performance in non‐trivial case studies and compare it with existing dynamic software update approaches. Copyright © 2012 John Wiley & Sons, Ltd.     

A Material Model for TRIP‐Steels and its Application to a CrMnNi Cast Alloy

A material model is presented that accounts for strain rate dependent inelastic deformation and strain‐induced phase transformation in TRIP‐steels. Modifications for the kinetics equations of the strain‐induced phase transformation, introduced by Stringfellow, are proposed to overcome a drawback of Stringfellow's model. A parameter identification strategy that relies on Gauss‐Markov estimates is used to determine the model parameters from experimental data of a recently developed cast TRIP‐steel. Good agreement is observed between experimental results of the compression test and the corresponding finite element simulation employing the proposed model. This forms the basis for future applications of the material model in the design of composites and structures.     

Absorption of acrylates and polysilazanes in the far UVC and the VUV regions

A simple but reliable method was developed for the determination of wavelength-dependent absorption coefficients in the vacuum-UV (VUV) spectral range 160 nm < λ < 195 nm.     

The Deubiquitinase OTUB1 Is a Key Regulator of Energy Metabolism

Dysregulated energy metabolism is a major contributor to a multitude of pathologies, including obesity and diabetes. Understanding the regulation of metabolic homeostasis is of utmost importance for the identification of therapeutic targets for the treatment of metabolically driven diseases. We previously identified the deubiquitinase OTUB1 as substrate for the cellular oxygen sensor factor-inhibiting HIF (FIH) with regulatory effects on cellular energy metabolism, but the physiological relevance of OTUB1 is unclear. Here, we report that the induced global deletion of OTUB1 in adult mice (Otub1 iKO) elevated energy expenditure, reduced age-dependent body weight gain, facilitated blood glucose clearance and lowered basal plasma insulin levels. The respiratory exchange ratio was maintained, indicating an unaltered nutrient oxidation. In addition, Otub1 deletion in cells enhanced AKT activity, leading to a larger cell size, higher ATP levels and reduced AMPK phosphorylation. AKT is an integral part of insulin-mediated signaling and Otub1 iKO mice presented with increased AKT phosphorylation following acute insulin administration combined with insulin hypersensitivity. We conclude that OTUB1 is an important regulator of metabolic homeostasis.     

Field classification of publications in Dimensions: a first case study testing its reliability and validity

Dimensions is a research data infrastructure and tool, including grants, publications, citations, clinical trials, and patents in one place. An interesting feature of Dimensions is its field classification scheme, which is not based on journal classification systems, as in the Web of Science or Scopus, but on machine learning. Each publication is assigned to at least one field. Using the set of my own publications, I investigated whether they were reliably and validly assigned to fields. The results put in question the reliability and validity of the scheme. Large scale studies seem necessary to investigate the scheme in more detail.

     

Discontinuities in citation relations among journals: self-organized criticality as a model of scientific revolutions and change

Scientometrics - Using 3-year moving averages of the complete Journal Citation Reports 1994–2016 of the Science Citation Index and the Social Sciences Citation Index (combined), we analyze...