Identifizierung VHL-assoziierter Veränderungen im klarzelligen Nierenzellkarzinom: Anwendung von kombinierten Genom- und Expressionsanalysen

Zusammenfassung: Das sporadische Nierenzellkarzinom (NZK) ist ein heterogener solider Tumor, der traditionell basierend auf morphologischen Kriterien in weitere Subtypen unterteilt wird. In den letzten Jahren konnten unter Anwendung molekularer Hochdurchsatzanalysen genetische, transkriptionelle und translationale Alterationen identifiziert werden. Diese Marker eignen sich zum einen für die molekulare Klassifizierung des NZK und haben zum anderen prognostische Wertigkeit. Die isolierte Betrachtung genetischer, transkriptioneller und translationaler Veränderungen verhindert jedoch ein tieferes Verständnis für die komplexen Vorgänge der Karzinogenese. Wir fassen hier aktuelle Forschungsergebnisse zur molekularen Charakterisierung des NZK zusammen und stellen ein systembiologisches Konzept zur Identifizierung neuer Tumormarker vor. Diese könnten zukünftig Einsatz in der Diagnostik und Therapie des sporadischen NZK finde

Von-Hippel-Lindau-Gen-Mutationstypen: Assoziation mit Genexpressionssignaturen in klarzelligen Nierenzellkarzinomen

Zusammenfassung: Fragestellung: Der Von-Hippel-Lindau- (VHL-)Tumorsuppressor ist ein multifunktionelles Protein. VHL-Mutationen treten häufig auf im klarzelligen Nierenzellkarzinom (kNZK). Verschiedene Mutationstypen führen vermutlich zu spezifischen pVHL-Funktionsveränderungen, die wiederum einen signifikanten Einfluss auf die Genexpression und schließlich auf den Krankheitsverlauf haben dürften. Ziel der vorliegenden Studie ist die Korrelation von Genexpressionssignaturen mit spezifischen VHL-Mutationstypen im kNZK. Methodik: Transkriptomanalyse wurde für 94 kNZK und 21 papilläre NZK (pNZK) mittels Affymetrix HG U133A Genchips durchgeführt. Alle 94 kNZK wurden auf VHL-Mutationen analysiert. Ergebnisse: Ein "hierarchical clustering" anhand der zwischen kNZK und pNZK differenziell regulierten Gene zeigt eine deutliche Stratifizierung der beiden histologischen Subtypen. 186 Gene wurden zwischen VHL-Wildtyp kNZK und kNZK mit mutiertem VHL-Gen differenziell exprimiert. Schlussfolgerung: Unsere Resultate weisen auf eine signifikante Auswirkung von VHL-Mutationen auf die Genexpression im NZK hi

WAO guideline for the management of hereditary angioedema

Hereditary Angioedema (HAE) is a rare disease and for this reason proper diagnosis and appropriate therapy are often unknown or not available for physicians and other health care providers. For this reason we convened a group of specialists that focus upon HAE from around the world to develop not only a consensus on diagnosis and management of HAE, but to also provide evidence based grades, strength of evidence and classification for the consensus. Since both consensus and evidence grading were adhered to the document meets criteria as a guideline. The outcome of the guideline is to improve diagnosis and management of patients with HAE throughout the world and to help initiate uniform care and availability of therapies to all with the diagnosis no matter where the residence of the individual with HAE exists

Condensation of a tetrahedra rigid-body libration mode in HoBaCo4O7 : the origin of phase transition at 355 K

Rietveld profiles, Moessbauer spectra and x-ray absorption fine structure (XAFS) were analyzed through the structural phase transition at Ts = 355 K in HoBaCo4O7. Excess of the oxygen content over O7 was avoided via annealing the samples in argon flow at 600 degree C. Space groups (S.G.) Pbn21c and P63mc were used to refine the structure parameters in the low- and high-temperature phases, respectively. Additionally, the Cmc21 symmetry was considered as a concurrent model of structure of the low-temperature phase. In the high-temperature phase, severe anisotropy of thermal motion of the major part of the oxygen atoms was observed. This anisotropic motion turns to be quenched as the sample is cooled below Ts. The variation of quadrupole splitting near Ts is not similar to a steplike anomaly frequently seen at the charge-ordering transition. We observe instead a dip-like anomaly of the average quadrupole splitting near Ts. Narrow distribution of the electric field gradient (EFG) over different cobalt sites is observed and explained on the basis of point-charge model. XAFS spectra show no evidence of significant difference between YBaCo4O7 (T > Ts) and HoBaCo4O7 (T < Ts). The origin of the transition at Ts is ascribed to the condensation of the libration phonon mode associated with the rigid-body rotational movements of the starlike tetrahedral units, the building blocks of kagome network. It is shown that the condensation of the libration mode is not compatible with translation symmetry for the hexagonal S.G., but compatible for the orthorhombic S.G. The orthorhombic lattice parameters and EFG components (Vxx, Vyy, Vzz) vary smoothly with temperature at approaching Ts and closely follow each other.Comment: 13 figure

Natural killer cells in afferent lymph express an activated phenotype and readily produce IFN-γ

Natural killer (NK) cells are motile cells that migrate between peripheral blood (PB), lymph nodes (LNs) and various organs. Domestic animals have frequently been used to study cellular migration, and offer unique opportunities for such studies. The aim of this study was to characterize the phenotype and cytokine producing capacity of NK cells in bovine skin-draining lymph. NKp46/NCR1+ CD3- cells constituted 2-11 % of mononuclear cells in afferent lymph (AL), a majority of cells were CD16+, CD8α+ and CD2-/low, and elevated CD25 and CD44 expression indicated an activated phenotype. Interestingly, significantly fewer AL NK cells expressed the early activation marker CD69 compared to PB NK cells. A large proportion of lymph and blood NK cells produced interferon (IFN)-γ following stimulation with IL-2 and IL-12. Notably, in AL, but not blood, a similar amount of IFN-γ+ NK cells was observed when cells were stimulated with IL-12 alone. Overall, AL NK cells were more similar to LN-residing NK cells than those circulating in PB. We conclude that AL appears to be an important migration route for tissue-activated NK cells, and may represent an alternative route for NK cell traffic to LNs. These findings may have important implications in the development of adjuvant strategies that aim to target NK cells in a vaccine response

A Mixed-Integer Linear Programming Model for Transportation Planning in the Full Truck Load Strategy to Supply Products with Unbalanced Demand in the Just in Time Context: A Case Study

[EN] Growing awareness in cutting transport costs and minimizing the environmental impact means that companies are increasingly interested in using the full truck load strategy in their supply tasks. This strategy consists of filling trucks completely with one product type or a mixture of products from the same supplier. This paper aims to propose a mixed-integer linear programming model and procedure to fill trucks which considers limitations of stocks, stock levels and unbalanced demand and minimization of the total number of trucks used in the full truck load strategy. The results obtained from a case study are presented and are exported in a conventional spreadsheet available for a company in the automotive industry.Maheut ., JP.; García Sabater, JP. (2013). A Mixed-Integer Linear Programming Model for Transportation Planning in the Full Truck Load Strategy to Supply Products with Unbalanced Demand in the Just in Time Context: A Case Study. IFIP Advances in Information and Communication Technology. 397:576-583. doi:10.1007/978-3-642-40361-3_73S576583397Bitran, G.R., Haas, E.A., Hax, A.C.: Hierarchical production planning: a single stage system. Operations Research 29, 717–743 (1981)Sun, H., Ding, F.Y.: Extended data envelopment models and a practical tool to analyse product complexity related to product variety for an automobile assembly plant. International Journal of Logistics Systems and Management 6, 99–112 (2010)Boysen, N., Fliedner, M.: Cross dock scheduling: Classification, literature review and research agenda. Omega 38, 413–422 (2010)Garcia-Sabater, J.P., Maheut, J., Garcia-Sabater, J.J.: A two-stage sequential planning scheme for integrated operations planning and scheduling system using MILP: the case of an engine assembler. Flexible Services and Manufacturing Journal 24, 171–209 (2012)Ben-Khedher, N., Yano, C.A.: The Multi-Item Replenishment Problem with Transportation and Container Effects. Transportation Science 28, 37–54 (1994)Cousins, P.D.: Supply base rationalisation: myth or reality? European Journal of Purchasing Supply Management 5, 143–155 (1999)Kiesmüller, G.P.: A multi-item periodic replenishment policy with full truckloads. International Journal of Production Economics 118, 275–281 (2009)Goetschalckx, M.: Transportation Systems Supply Chain Engineering, vol. 161, pp. 127–154. Springer, US (2011)Liu, R., Jiang, Z., Fung, R.Y.K., Chen, F., Liu, X.: Two-phase heuristic algorithms for full truckloads multi-depot capacitated vehicle routing problem in carrier collaboration. Computers Operations Research 37, 950–959 (2010)Arunapuram, S., Mathur, K., Solow, D.: Vehicle Routing and Scheduling with Full Truckloads. Transportation Science 37, 170–182 (2003