LEVERAGING IN-MEMORY TECHNOLOGY TO IMPROVE THE ACCEPTANCE OF MSS - A MANAGERS´ PERSPECTIVE

Management support systems (MSS) help managers to perform their jobs more efficiently. With in-memory technology, a new IT enabler promises to support managers by benefits ranging from reducing time for MSS data entry and analysis to completing even new topics of analysis. Hence, the present situation is favorable for an MSS redesign applying in-memory apps. Such apps are field-tested and ready-to-use, but from a business perspective they lack impact. Based on findings from a literature review and results from a workshop with an expert focus group validated with one-on-one manager interviews, we propose four initial use situations in which in-memory apps contribute to greater MSS acceptance: (1) In-memory apps should accelerate the MSS response time for both check status and receive an alert. In doing so, they should focus on information from management accounting. (2) By delivering information more timely, in-memory apps should contribute to MSS standard reports and financial closing. (3) In-memory apps should accelerate MSS response time for both ad-hoc analysis and drill-down/drill-through analysis. (4) Leveraging in-memory apps, MSS ad-hoc analysis and drill down/drill-through analysis should become more flexible.

The Sodium/Proline Transporter PutP of Helicobacter pylori

Helicobacter pylori is cause of chronic gastritis, duodenal ulcer and gastric carcinoma in humans. L-proline is a preferred energy source of the microaerophilic bacterium. Previous analyses revealed that HpputP and HpputA, the genes that are predicted to play a central role in proline metabolism as they encode for the proline transporter and proline dehydrogenase, respectively, are essential for stomach colonization. Here, the molecular basis of proline transport in H. pylori by HpPutP was investigated experimentally for the first time. Measuring radiolabeled substrate transport in H. pylori and E. coli heterologously expressing HpputP as well as in proteoliposomes reconstituted with HpPutP, we demonstrate that the observed proline transport in H. pylori is mediated by HpPutP. HpPutP is specific and exhibits a high affinity for L-proline. Notably, L-proline transport is exclusively dependent on Na+ as coupling ion, i.e., Na+/L-proline symport, reminiscent to the properties of PutP of E. coli even though H. pylori lives in a more acidic environment. Homology model-based structural comparisons and substitution analyses identified amino acids crucial for function. HpPutP-catalyzed proline uptake was efficiently inhibited by the known proline analogs 3,4-dehydro-D,L-proline and L-azetidine-2-carboxylic acid

Clinical Application of fluorescence lifetime imaging at the eye

Publikation entstand im Rahmen der Veranstaltung: 4th Workshop on advanced microscopic imaging methods, Shenzhen(China), 201

The TANAMI Program

TANAMI (Tracking Active Galactic Nuclei with Austral Milliarcsecond Interferometry) is a monitoring program to study the parsec-scale structures and dynamics of relativistic jets in active galactic nuclei (AGN) of the Southern Hemisphere with the Long Baseline Array and associated telescopes. Extragalactic jets south of -30 degrees declination are observed at 8.4 GHz and 22 GHz every two months at milliarcsecond resolution. The initial TANAMI sample is a hybrid radio and gamma-ray selected sample since the combination of VLBI and gamma-ray observations is crucial to understand the broadband emission characteristics of AGN.Comment: Confernce Proceedings for "X-ray Astronomy 2009" (Bologna), 3 pages, 3 figures, needs cls-fil

TANAMI monitoring of Centaurus A: The complex dynamics in the inner parsec of an extragalactic jet

Context. Centaurus A (Cen A) is the closest radio-loud active galactic nucleus. Very Long Baseline Interferometry (VLBI) enables us to study the spectral and kinematic behavior of the radio jet¿counterjet system on milliarcsecond scales, providing essential information for jet emission and propagation models. Aims. In the framework of the TANAMI monitoring, we investigate the kinematics and complex structure of Cen A on subparsec scales. We have been studying the evolution of the central parsec jet structure of Cen A for over 3.5 years. The proper motion analysis of individual jet components allows us to constrain jet formation and propagation and to test the proposed correlation of increased high-energy flux with jet ejection events. Cen A is an exceptional laboratory for such a detailed study because its proximity translates to unrivaled linear resolution, where one milliarcsecond corresponds to 0.018 pc. Methods. As a target of the southern-hemisphere VLBI monitoring program TANAMI, observations of Cen A are done approximately every six months at 8.4 GHz with the Australian Long Baseline Array (LBA) and associated telescopes in Antarctica, Chile, New Zealand, and South Africa, complemented by quasi-simultaneous 22.3 GHz observations. Results. The first seven epochs of high-resolution TANAMI VLBI observations at 8.4 GHz of Cen A are presented, resolving the jet on (sub-)milliarcsecond scales. They show a differential motion of the subparsec scale jet with significantly higher component speeds farther downstream where the jet becomes optically thin. We determined apparent component speeds within a range of 0.1c to 0.3c and identified long-term stable features. In combination with the jet-to-counterjet ratio, we can constrain the angle to the line of sight to theta approx 12deg-45deg. Conclusions. The high-resolution kinematics are best explained by a spine-sheath structure supported by the downstream acceleration occurring where the jet becomes optically thin. On top of the underlying, continuous flow, TANAMI observations clearly resolve individual jet features. The flow appears to be interrupted by an obstacle causing a local decrease in surface brightness and circumfluent jet behavior. We propose a jet-star interaction scenario to explain this appearance. The comparison of jet ejection times to high X-ray flux phases yields a partial overlap of the onset of the X-ray emission and increasing jet activity, but the limited data do not support a robust correlation

Structure-based analysis of CysZ-mediated cellular uptake of sulfate

Sulfur, most abundantly found in the environment as sulfate (SO42-), is an essential element in metabolites required by all living cells, including amino acids, co-factors and vitamins. However, current understanding of the cellular delivery of SO42- at the molecular level is limited. CysZ has been described as a SO42- permease, but its sequence family is without known structural precedent. Based on crystallographic structure information, SO42- binding and flux experiments, we provide insight into the molecular mechanism of CysZ-mediated translocation of SO42- across membranes. CysZ structures from three different bacterial species display a hitherto unknown fold and have subunits organized with inverted transmembrane topology. CysZ from Pseudomonas denitrificans assembles as a trimer of antiparallel dimers and the CysZ structures from two other species recapitulate dimers from this assembly. Mutational studies highlight the functional relevance of conserved CysZ residues

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival