Balancing Access to Data And Privacy. A review of the issues and approaches for the future

Access to sensitive micro data should be provided using remote access data enclaves. These enclaves should be built to facilitate the productive, high-quality usage of microdata. In other words, they should support a collaborative environment that facilitates the development and exchange of knowledge about data among data producers and consumers. The experience of the physical and life sciences has shown that it is possible to develop a research community and a knowledge infrastructure around both research questions and the different types of data necessary to answer policy questions. In sum, establishing a virtual organization approach would provided the research community with the ability to move away from individual, or artisan, science, towards the more generally accepted community based approach. Enclave should include a number of features: metadata documentation capacity so that knowledge about data can be shared; capacity to add data so that the data infrastructure can be augmented; communication capacity, such as wikis, blogs and discussion groups so that knowledge about the data can be deepened and incentives for information sharing so that a community of practice can be built. The opportunity to transform micro-data based research through such a organizational infrastructure could potentially be as far-reaching as the changes that have taken place in the biological and astronomical sciences. It is, however, an open research question how such an organization should be established: whether the approach should be centralized or decentralized. Similarly, it is an open research question as to the appropriate metrics of success, and the best incentives to put in place to achieve success.Methodology for Collecting, Estimating, Organizing Microeconomic Data

Balancing Access to Data and Privacy: a review of the issues and approaches for the future

"Access to sensitive micro data should be provided using remote access data enclaves. These enclaves should be built to facilitate the productive, high-quality usage of microdata. In other words, they should support a collaborative environment that facilitates the development and exchange of knowledge about data among data producers and consumers. The experience of the physical and life sciences has shown that it is possible to develop a research community and a knowledge infrastructure around both research questions and the different types of data necessary to answer policy questions. In sum, establishing a virtual organization approach would provided the research community with the ability to move away from individual, or artisan, science, towards the more generally accepted community based approach. Enclave should include a number of features: metadata documentation capacity so that knowledge about data can be shared; capacity to add data so that the data infrastructure can be augmented; communication capacity, such as wikis, blogs and discussion groups so that knowledge about the data can be deepened and incentives for information sharing so that a community of practice can be built. The opportunity to transform micro-data based research through such a organizational infrastructure could potentially be as far-reaching as the changes that have taken place in the biological and astronomical sciences. It is, however, an open research question how such an organization should be established: whether the approach should be centralized or decentralized. Similarly, it is an open research question as to the appropriate metrics of success, and the best incentives to put in place to achieve success." (author's abstract

On satellites in semi-abelian categories: Homology without projectives

Working in a semi-abelian context, we use Janelidze's theory of generalised satellites to study universal properties of the Everaert long exact homology sequence. This results in a new definition of homology which does not depend on the existence of projective objects. We explore the relations with other notions of homology, and thus prove a version of the higher Hopf formulae. We also work out some examples.Comment: 29 pages; major changes in Example 4.15, minor changes throughout the tex

Analytical and Biological Investigation of Novel Titanium(IV) and Platinum(II) Complexes as Potential Anticancer Agents

Nach Herz-Kreislauferkrankungen sind Krebserkankungen die zweithäufigste Todesursache in Deutschland. Trotz der guten medikamentösen Behandlungsmöglichkeit, besteht nach wie vor ein hoher Bedarf nach der Entwicklung alternativer Arzneistoffe mit einem andersartigen Wirkmechanismus. Eine vielversprechende Alternative stellen antitumoraktive Titan(IV)-Komplexe mit Cyclopentadienyl- bzw. Salan-Liganden sowie neuartige Platin(II)-Komplexe mit Phenacetylid-Liganden dar. Über die biologischen Eigenschaften und das Target dieser neuen Substanzfamilien ist nur wenig bekannt, was im Hinblick auf deren möglichen Einsatz in der Tumortherapie zwingend notwendig ist. Deshalb wurden biochemische Untersuchungen zur Aufklärung des bisher unbekannten Wirkmechanismus der neuen Substanzfamilien durchgeführt. Dazu wurde eine auf der hochauflösenden Atomabsorptionsspektrometrie beruhende Analysemethode zur sensitiven Metallquantifizierung in biologischem Material entwickelt. Die Titan(IV)-Komplexe zeigten abhängig vom gewählten Liganden ein unterschiedliches Verhalten bezüglich ihrer Toxizität, Affinität zu Biomolekülen (DNA, Serumalbumin) und intrazellulären Bioverteilung. Eine besonders hohe serumabhängige Zellaufnahme und eine Akkumulation in den Mitochondrien konnte für den Titankomplex mit Salan-Ligand beobachtet werden. Der Titankomplex mit Cyclopentadienyl-Ligand wies eine nur geringe Zellaufnahme, aber hohe Affinität zu Biomolekülen sowie eine Lokalisation in den Zellkernen auf. Die erstmalige biologische Charakterisierung der neu synthetisierten Platin(II)-Alkinyl-Komplexe lieferte eine hohe antiproliferative Potenz gegen Tumorzellen. Im Hinblick auf eine Targetidentifizierung konnte die DNA als ein mögliches Zielmolekül identifiziert werden. Besonders vielversprechend ist außerdem die für Platinkomplexe bisher unbekannte hohe inhibitorische Aktivität der Platin(II)-Alkinyl-Komplexe gegen das Selenoenzym Thioredoxinreduktase, die einen andersartigen Wirkmechanismus vermuten lässt.After cardiovascular diseases the second leading cause of death in Germany is cancer. Despite there are several therapeutic options available, there is still a strong need to develop new pharmaceuticals that overcome the severe side effects and resistance phenomena of nowadays used anticancer drugs. Titanium(IV) complexes with salan or cyclopentadienyl ligands and platinum(II) compounds with alkynyl ligands have shown a promising potential. For further development of these novel compound classes a chemical-biological evaluation was strongly needed. Therefore, their reactivity against biomolecules and enzymes, their cellular accumulation and distribution as well as their in vitro- and in vivo-toxicity was studied. In addition, a method to quantify metals in biological material using high-resolution continuum-source atomic absorption spectroscopy was developed. The investigation of cytotoxic titanium(IV) complexes with a salan or cyclopentadienyl ligand indicated a very different biological behavior. The titanium compound with salan ligand showed low binding affinities to DNA and albumin but a high and serum dependent cellular accumulation as well as high titanium levels in mitochondria. In contrast, the titanium complex with cyclopentadienyl ligand afforded a generally lower cellular uptake with increased binding efficacy to biomolecules and a nuclear accumulation. The biological investigation of platinum(II) complexes with alkynyl ligands revealed a high antiproliferative potency of this novel compound class against cancer cells. Furthermore, the DNA was identified as potential target. With respect to their properties as selective thioredoxin reductase inhibitors a different mode of action in comparison to known platinum based drugs was found. Overall these results clearly demonstrate the high potential of novel titanium(IV) complexes with salan or cyclopentadienyl ligands and platinum(II) complexes with alkynyl ligands as potential anticancer agents

Study of the effect of the chromophore and nuclearity on the aggregation and potential biological activity of gold(I) alkynyl complexes

The synthesis and characterization of four organometallic gold(I) complexes containing different water soluble phosphanes (TPPTS, PTA and DAPTA) and chromophoric units (4-pyridylethynyl and propargyloxycoumarin) is here reported. The analysis of their absorption and emission spectra led us to attribute their luminescent behavior to the chromophoric organic ligands. Moreover, the presence of the gold(I) metal atom has been observed to be the responsible of an efficient intersystem crossing process responsible for the observed phosphorescence emission. Broad emission bands are observed in most cases due to the formation of organized aggregates in solution in agreement with microscopic characterization.; Biological activity of the complexes showed very low effects against tumor cell growth but an inhibitory potency against thioredoxin reductase (TrxR). The missing/low cytotoxic effects could be related to a low bioavailability as determined by atomic absorption spectroscopy. (C) 2016 Elsevier B.V. All rights reserved.Postprint (author's final draft

The plant decapeptide OSIP108 can alleviate mitochondrial dysfunction induced by cisplatin in human cells

We investigated the effect of the Arabidopsis thaliana-derived decapeptide OSIP108 on human cell tolerance to the chemotherapeutic agent cisplatin (Cp), which induces apoptosis and mitochondrial dysfunction. We found that OSIP108 increases the tolerance of HepG2 cells to Cp and prevents Cp-induced changes in basic cellular metabolism. More specifically, we demonstrate that OSIP108 reduces Cp-induced inhibition of respiration, decreases glycolysis and prevents Cp-uptake in HepG2 cells. Apart from its protective action against Cp in human cells, OSIP108 also increases the yeast Saccharomyces cerevisiae tolerance to Cp. A limited yeast-based study of OSIP108 analogs showed that cyclization does not severely affect its activity, which was further confirmed in HepG2 cells. Furthermore, the similarity in the activity of the D-stereoisomer (mirror image) form of OSIP108 with the L stereoisomer suggests that its mode of action does not involve binding to a stereospecific receptor. In addition, as OSIP108 decreases Cp uptake in HepG2 cells and the anti-Cp activity of OSIP108 analogs without free cysteine is reduced, OSIP108 seems to protect against Cp-induced toxicity only partly via complexation. Taken together, our data indicate that OSIP108 and its cyclic derivatives can protect against Cp-induced toxicity and, thus, show potential as treatment options for mitochondrial dysfunction- and apoptosis-related conditions

Qualitative Examination of Voting Empowerment and Participation Among People Living With Traumatic Brain Injury

Objective To examine political participation after traumatic brain injury (TBI). Design Qualitative, participatory research via interviews and observations. Each participant was interviewed to discuss their experience of voting in 2007 or 2008. Data were coded using Grounded Theory to develop themes, metacodes, and theories. Setting Community. Participants A total of 57 individuals with history of TBI and 28 family members (N=85). Main Outcome Measures Not applicable. Results Four themes emerged from the data: (1) people with TBI have barriers to voting; (2) the voting process can be improved for people with TBI; (3) voting is the responsibility of members of society; and (4) voting is one way we have a voice in society. Conclusions The data support the importance of voting as an American right regardless of the presence of disability. While persons with TBI report voting represents their freedom and voice, there may be barriers that can threaten or limit their voice

PEER Amendment to Appendix C: D3.1

This is an amendment to the deliverable D3.1 Guidelines (published in May 2009) - Appendix C: Author communication texts

Platinum alkynyl complexes: Cellular uptake, inhibition of thioredoxin reductase and toxicity in zebrafish embryos

Cytotoxic platinum(II) alkynyl complexes of the type [(COD)Pt(Me)(C CR)] and [(COD)Pt(C CR)2] were evaluated for their cellular uptake, thioredoxin reductase (TrxR) inhibition and toxicity against zebrafish embryos. Quantification of the cellular uptake confirmed lower accumulation levels for the mono-alkynyl derivatives [(COD)Pt(Me)(C CR)] in comparison to the bis-alkynyl complexes [(COD)Pt(C CR)(2)]. Importantly, the complexes were efficient inhibitors of TrxR in contrast to cisplatin, which was not active. Toxicity studies in zebrafish showed lower activity if compared with the cytotoxicity against tumor cells indicating a suitable therapeutic index for the complexes

Fe-III, Cu-II and Zn-II Complexes of the Rigid 9-Oxido-phenalenone Ligand-Spectroscopy, Electrochemistry, and Cytotoxic Properties

The three complexes [Fe(opo)(3)], [Cu(opo)(2)], and [Zn(opo)(2)] containing the non-innocent anionic ligand opo(-) (opo(-) = 9-oxido-phenalenone, Hopo = 9-hydroxyphenalonone) were synthesised from the corresponding acetylacetonates. [Zn(opo)(2)] was characterised using H-1 nuclear magnetic resonance (NMR) spectroscopy, the paramagnetic [Fe(opo)(3)] and [Cu(opo)(2)] by electron paramagnetic resonance (EPR) spectroscopy. While the EPR spectra of [Cu(opo)(2)] and [Cu(acac)(2)] in dimethylformamide (DMF) solution are very similar, a rather narrow spectrum was observed for [Fe(opo)(3)] in tetrahydrofuran (THF) solution in contrast to the very broad spectrum of [Fe(acac)(3)] in THF (Hacac = acetylacetone, 2,4-pentanedione; acac(-) = acetylacetonate). The narrow, completely isotropic signal of [Fe(opo)(3)] disagrees with a metal-centred S = 5/2 spin system that is observed in the solid state. We assume spin-delocalisation to the opo ligand in the sense of an opo(-) to Fe-III electron transfer. All compounds show several electrochemical opo-centred reduction waves in the range of -1 to -3 V vs. the ferrocene/ferrocenium couple. However, for Cu-II and Fe-III the very first one-electron reductions are metal-centred. Electronic absorption in the UV to vis range are due to pi-pi* transitions in the opo core, giving Hopo and [Zn(opo)(2)] a yellow to orange colour. The structured bands ranging from 400 to 500 for all compounds are assigned to the lowest energy pi-pi* transitions. They show markedly higher intensities and slight shifts for the Cu-II (brown) and Fe-III (red) complexes and we assume admixing metal contributions (MLCT for Cu-II, LMCT for Fe-III). For both complexes long-wavelength absorptions assignable to d-d transitions were detected. Detailed spectroelectrochemical experiments confirm both the electrochemical and the optical assignments. Hopo and the complexes [Cu(opo)(2)], [Zn(opo)(2)], and [Fe(opo)(3)] show antiproliferative activities against HT-29 (colon cancer) and MCF-7 (breast cancer) cell lines in the range of a few mu M, comparable to cisplatin under the same conditions