Do Rankings Reflect Research Quality?

Publication and citation rankings have become major indicators of the scientific worth of universities and countries, and determine to a large extent the career of individual scholars. We argue that such rankings do not effectively measure research quality, which should be the essence of evaluation. For that reason, an alternative ranking is developed as a quality indicator, based on membership on academic editorial boards of professional journals. It turns out that especially the ranking of individual scholars is far from objective. The results differ markedly, depending on whether research quantity or research quality is considered. Even quantity rankings are not objective; two citation rankings, based on different samples, produce entirely different results. It follows that any career decisions based on rankings are dominatedby chance and do not reflect research quality. Instead of propagating a ranking based on board membership as the gold standard, we suggest that committees make use of this quality indicator to find members who, in turn, evaluate the research quality of individual scholars.rankings, universities, scholars, publications, citations

Lack of increased availability of root-derived C may explain the low N2O emission from low N-urine patches

Urine deposition on grassland causes significant N2O losses, which in some cases may result from increased denitrification stimulated by labile compounds released from scorched plant roots. Two 12-day experiments were conducted in 13C-labelled grassland monoliths to investigate the link between N2O production and carbon mineralization following application of low rates of urine-N. Measurements of N2O and CO2 emissions from the monoliths as well as δ13C signal of evolved CO2 were done on day -4, -1, 0, 1, 2, 4, 5, 6 and 7 after application of urine corresponding to 3.1 and 5.5 g N m-2 in the first and second experiment, respectively. The δ13C signal was also determined for soil organic matter, dissolved organic C and CO2 evolved by microbial respiration. In addition, denitrifying enzyme activity (DEA) and nitrifying enzyme activity (NEA) were measured on day -1, 2 and 7 after the first urine application event. Urine did not affect DEA, whereas NEA was enhanced 2 days after urine application. In the first experiment, urine had no significant effect on the N2O flux, which was generally low (-8 to 14 μg N2O-N m-2 h-1). After the second application event, the N2O emission increased significantly to 87 μg N2O-N m-2 h-1 and the N2O emission factor for the added urine-N was 0.18 %. However, the associated 13C signal of soil respiration was unaffected by urine. Consequently, the increased N2O emission from the simulated low N-urine patches was not caused by enhanced denitrification stimulated by labile compounds released from scorched plant roots

Electrochemical detection of the toxic dinoflagellate Alexandrium ostenfeldii with a DNA-biosensor

The steady rise of observations of harmful or toxic algal blooms throughout the world in the past decades constitute a menace for coastal ecosystems and human interests. As a consequence, a number of programs have been launched to monitor the occurrence of harmful and toxic algae. However, the identification is currently done by microscopic examination, which requires a broad taxonomic knowledge, expensive equipment and is very time consuming. In order to facilitate the identification of toxic algae, an inexpensive and easy-to-handle DNA-biosensor has been adapted for the electrochemical detection of the toxic dinoflagellate Alexandrium ostenfeldii. The detection of the toxic algae is based on a sandwich hybridisation, which is carried out on a disposable sensor chip. A set of two probes for the species specific identification of A. ostenfeldii was developed. The specificity of the probes could be shown in dot-blot hybridisation and with the DNA-biosensor. The sensitivity of the DNA-biosensor was optimised with respect to hybridisation temperature and NaCl-concentration and a significant increase of the sensitivity of the DNA-biosensor could be obtained by a fragmentation of the rRNA prior to the hybridisation and by adding a helper oligonucleotide, which binds in close proximity to the probes to the hybridisation

The subdiffusive target problem: Survival probability

The asymptotic survival probability of a spherical target in the presence of a single subdiffusive trap or surrounded by a sea of subdiffusive traps in a continuous Euclidean medium is calculated. In one and two dimensions the survival probability of the target in the presence of a single trap decays to zero as a power law and as a power law with logarithmic correction, respectively. The target is thus reached with certainty, but it takes the trap an infinite time on average to do so. In three dimensions a single trap may never reach the target and so the survival probability is finite and, in fact, does not depend on whether the traps move diffusively or subdiffusively. When the target is surrounded by a sea of traps, on the other hand, its survival probability decays as a stretched exponential in all dimensions (with a logarithmic correction in the exponent for $d=2$). A trap will therefore reach the target with certainty, and will do so in a finite time. These results may be directly related to enzyme binding kinetics on DNA in the crowded cellular environment.Comment: 6 pages. References added, improved account of previous results and typos correcte

Murine leukemia virus (MLV) replication monitored with fluorescent proteins

Background: Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV) has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results: We inserted the coding sequences for green fluorescent protein (GFP) into the proline-rich region (PRR) of the ecotropic envelope protein (Env) and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP) and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions: Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy

Universality of efficiency at maximum power

We investigate the efficiency of power generation by thermo-chemical engines. For strong coupling between the particle and heat flows and in the presence of a left-right symmetry in the system, we demonstrate that the efficiency at maximum power displays universality up to quadratic order in the deviation from equilibrium. A maser model is presented to illustrate our argument.Comment: 4 pages, 2 figure

Divergent Synthesis of Indolo[3,2- c]quinolines, Neocryptolepines and Related Tetracyclic Ring-Systems Containing Promising Biological Activities

Malaria is a devastating tropical disease, claiming approximately 627 000 lives in 2020. Due to the appearance of resistance towards artemisinin-based therapies, the discovery of novel treatments are of paramount importance. The indoloquinoline natural products cryptolepine, neocryptolepine and isocryptolepine, first discovered in the extracts of the African bush plant Cryptolepis sanguinolenta, have been found to exhibit potent antimalarial properties. More-over, several functionalized derivatives of these compounds have shown great promise as antiplasmodial agents. The indoloquinoline alkaloids have also been found to possess significant antiproliferative and antimicrobial properties, making them ideal targets for the development into novel drug candidates. The first project in this work details the application of a synthetic approach first developed by Helgeland and Sydnes to assemble various tetracyclic ring systems. The key synthetic strategies being a Suzuki-Miyaura cross-coupling reaction followed by a palladium-catalyzed intramolecular cyclization. Though the approach was unsuitable to construct all the intended target molecules, it furnished the unexpected pyridophenanthridine scaffold. By further investigating alternative protocols for the construction of indoloquinolines, a regiodivergent intermediate was discovered, which allowed for the synthesis of both novel pyridophenanthridineand pyridocarbazole scaffolds by utilizing two different reaction protocols. By subjecting this common intermediate to a diazotization-azidation-nitrene insertion approach, the novel pyrido-carbazoles could be furnished in excellent yields. The unexpected formation of a biquinoline bridged by an aniline during a Suzuki-Miyaura cross-coupling reaction, was deemed interesting for development into a transition metal complex for catalysis. Through a collaborative effort with Dr. Eugene Khaskin’s group at Okinawa Institute of Science and Technology, five quinoline/pyridine N,N,N ligands were designed and synthesized. The key synthetic tools utilized in their construction was either a sequential Suzuki-Miyaura cross-coupling reaction and Buchwald-Hartwig amination or reductive amination. A novel two-step approach for the synthesis of the natural product neocryptolepine from commercially available bromoquinolines was developed. The key transformations being regioselective N-alkylations followed by a cascade Suzuki-Miyaura cross-coupling reaction andintramolecular nucleophilic C-N bond formation. The scope and limitations for the novel protocol was evaluated through the preparation of 24 neocryptolepine derivatives, bearing a diverse range of functional groups, where electron-withdrawing group substitutions were generally superior. It became apparent that it would also be possible to prepare a library of indolo[3,2-c]quino-lines from the same starting material as the newly devised strategy to produce neocryptolepines. By utilizing a reaction sequence consisting of a Suzuki-Miyaura cross-coupling reaction, installation of an azido moiety and finally photochemical cyclization, this goal was realized, producing a total of 19 indoloquinolines. This protocol was less robost towards substrate functionalizations than the neocryptolepine approach, with no apparent trend concerning electron-withdrawing and electron-donating groups being apparent. The photochemical cyclization was hypothesized to proceed via the formation of a reactive singlet nitrene intermediate. Finally, a selection of the prepared tetracyclic compounds assembled during this work was evaluated for their antiplasmodial, antiproliferative and antimicrobial activities by the help of various external collaborators. The most successful compound was revealed to be the novel pyridophenanthridines, displaying more potent antiproliferative activities than doxoru-bicin against human prostate cancer (IC50= 24 nM). The novel pyridocarbazoles moreover showed excellent inhibition of biofilm formation, with the potential to be developed into a dualanticancer-antimicrobial agent. Of all the tested compounds, only N-methylated pyridocar-bazole was found to contain any significant activity against the evaluated Plasmodium falci-parumstrain. The antimicrobial assays revealed the importance of the inclusion of a methylgroup for activity, but not strictly in the form of an N-methyl unit, which is the general concensus in the literature thus far. Further, chlorinated indoloquinolines were revealed to contain excellent antimicrobial activity against both Gram-positive and Gram-negative bacterial celllines