La loza dorada medieval en la Península Ibérica. Aportaciones recientes a su evolución y nuevos datos para su cronología

Las producciones doradas de la Península Ibérica significan para la investigación cerámica una mercancía poco frecuente, susceptible de proporcionar, no obstante, abundante información tanto de tipo comercial como técnica y estilística. Son, a su vez, testimonios de un intercambio regular en el ámbito mediterráneo, que ya en el siglo X incluía con frecuencia productos cerámicos, tradicionalmente infravalorados por la investigación. En el marco del presente trabajo, junto a una más fácil sistematización de los diferentes grupos de importaciones, se ha pretendido esbozar, por primera vez y a través de un detallado estudio, la compleja evolución de la loza dorada. Se hace notar cuan sorprendentemente lejos llegaron los influjos de los centros de producción cerámica de máxima calidad entre el ámbito islámico oriental, el occidental y los territorios cristianos y cómo también en esta área la nueva “naciente” cultura cerámica –así como la correspondiente cultura material– sobrevivió a pesar incluso de los fundamentales cambios políticos.Zusammenfassend sei folgendes festgehalten: Die Lüsterwaren von der Iberischen Halbinsel bedeuten für die Keramikforschung ein fast einzigartiges Handwerksprodukt, an dem sich über die Jahrhunderte merkantile, technische und stilistische Informationen übermitteln. Sie sind Zeugnis eines regen Mittelmeerhandels, der bereits im 10. Jh. auch den oft unterbewerteten Werkstoff Keramik einschloss. Neben den einfacher zu formulierenden Importgruppen lässt sich die komplexe Entwicklung der Goldlüstertöpferei im Untersuchungsraum durch einen detaillierteren Ansatz nun erstmals skizzieren. Deutlich kann nachgewiesen werden, wie überraschend weit die Einfl üsse innerhalb des hochstehenden Töpfereihandwerks zwischen dem Ostislam, dem Westislam und dem Christentum reichen und wie eine im Gebiet neu entstandene Keramikkultur – wie auch die sonstige Sachkultur – sogar fundamentale politische Umbrüche überlebte

Taking the transformation pathway : food waste prevention measures in day-care centres in Copenhagen

We are currently using the planet’s limited resources in a very unsustainable way: around one-third of all food produced for human consumption is wasted each year, which has immense environmental, social and economic consequences. Even though ranked as one of the most sustainable countries in the world, Denmark still wastes annually food worth €1.1billion. To reduce the amount of food waste and all its consequences, preventing avoidable food waste is the most preferred option. With the help of the transition theory as well as the theory of the diffusion of innovations, this thesis explores how innovations to prevent food waste can lead to a more sustainable food waste regime. The thesis contributes therefore to sustainability science through linking research on problem structures with a solution-oriented approach that seeks to understand, diffuse and scale up food waste prevention measures. Destructive landscape changes, such as the financial crisis, global population growth, climate change and the ambitious future food waste reduction targets of the EU, cause an emerging visibility of food waste in all areas of society and put immense pressure on the underlying regime level. As suggested by the concept of transition pathways, regime actors, such as the government of Denmark and the city of Copenhagen, have started to react and adjust to the described landscape pressures. The identified innovation of food waste prevention measures in the case of day-care kitchens in Copenhagen tackles all main causes of food waste in the food service sector. If those innovations are stable and diffused to a certain extent, they might be adopted as add-ons by regime-actors. This can lead to a change of practices, an overall reduction of food waste and consequently to a transformation towards a more sustainable food waste regime. Regime actors could enhance the diffusion of the measures for example through the use of homophilous change agents, the promotion of perceived characteristics of the measures and the effective use of different communication channels

Neue mittelalterliche Erdstollen westlich von Sevilla. Südliche Beispiele für das mitteleuropäische Phänomen des Erdstalls

Der Beitrag behandelt neu aufgefundene Erdstollen, die durch ein Forschungsprojekt der Universitäten Bamberg und Sevilla in der almohadenzeitlichen Dorfwüstung von Cuatrovitas entdeckt worden sind. Noch während der Projektlaufzeit kamen weitere Beispiele durch Straßenbaumaßnahmen im näheren Umkreis hinzu. Eine wissenschaftliche Behandlung der Thematik ist von großem Interesse, blieb doch das Phänomen dieser einfachen Systeme aus Kriechgängen in Spanien bisher auf weite Sicht unberücksichtigt, obwohl diese offensichtlich zahlreicher waren als derzeit bekannt. Mit diesen neuen Beispielen aus dem Raum des sog. Aljarafe-Gebiets bei Sevilla lässt sich länderübergreifend eine Verbindung zum Typ des mitteleuropäischen Erdstalls herstellen, dessen Auftreten und Herausbildung in der intensiv betriebenen deutschsprachigen Erdstallforschung seit über 150 Jahren gesammelt und diskutiert wird. Seine Funktion als Zufluchtsstätte in hochmittelalterlichen Krisenzeiten kann inzwischen plausibel belegt werden.The paper concerns newly discovered underground galleries which were discovered during a research project of the universities of Bamberg and Sevilla in the Almohad period abandoned settlement of Cuatrovitas. While the project was still ongoing further examples in the region were discovered during road maintenance projects. A scientific study of the subject is of great importance, as the overview study of the phenomenon of a simple system of crawlspaces has up to now been neglected in Spain, even though they appear more numerous than believed. With these new examples from the area of the so-called Aljarafe region near Sevilla we can connect them to the type of central European souterrains, the appearance and genesis of which is being vigorously collected and discussed in the German language »Erdstall« research. Their fucntion as refuges during High Medieval crisis periods has been plausibly established

Bandwidth selection for kernel density estimation: a review of fully automatic selectors

On the one hand, kernel density estimation has become a common tool for empirical studies in any research area. This goes hand in hand with the fact that this kind of estimator is now provided by many software packages. On the other hand, since about three decades the discussion on bandwidth selection has been going on. Although a good part of the discussion is about nonparametric regression, this parameter choice is by no means less problematic for density estimation. This becomes obvious when reading empirical studies in which practitioners have made use of kernel densities. New contributions typically provide simulations only to show that the own selector outperforms some of the existing methods. We review existing methods and compare them on a set of designs that exhibit few bumps and exponentially falling tails. We concentrate on small and moderate sample sizes because for large ones the differences between consistent methods are often negligible, at least for practitioners. As a byproduct we find that a mixture of simple plug-in and cross-validation methods produces bandwidths with a quite stable performanc

The MLL-Menin Interaction is a Therapeutic Vulnerability in NUP98 -rearranged AML

Chromosomal translocations involving the NUP98 locus are among the most prevalent rearrangements in pediatric acute myeloid leukemia (AML). AML with NUP98 fusions is characterized by high expression of HOXA and MEIS1 genes and is associated with poor clinical outcome. NUP98 fusion proteins are recruited to their target genes by the mixed lineage leukemia (MLL) complex, which involves a direct interaction between MLL and Menin. Here, we show that therapeutic targeting of the Menin-MLL interaction inhibits the propagation of NUP98-rearrranged AML both ex vivo and in vivo. Treatment of primary AML cells with the Menin inhibitor revumenib (SNDX-5613) impairs proliferation and clonogenicity ex vivo in long-term coculture and drives myeloid differentiation. These phenotypic effects are associated with global gene expression changes in primary AML samples that involve the downregulation of many critical NUP98 fusion protein-target genes, such as MEIS1 and CDK6. In addition, Menin inhibition reduces the expression of both wild-type FLT3 and mutated FLT3-ITD, and in combination with FLT3 inhibitor, suppresses patient-derived NUP98-r AML cells in a synergistic manner. Revumenib treatment blocks leukemic engraftment and prevents leukemia-associated death of immunodeficient mice transplanted with NUP98::NSD1 FLT3-ITD-positive patient-derived AML cells. These results demonstrate that NUP98-rearranged AMLs are highly susceptible to inhibition of the MLL-Menin interaction and suggest the inclusion of AML patients harboring NUP98 fusions into the clinical evaluation of Menin inhibitors.</p

The MLL-Menin Interaction is a Therapeutic Vulnerability in NUP98 -rearranged AML

Chromosomal translocations involving the NUP98 locus are among the most prevalent rearrangements in pediatric acute myeloid leukemia (AML). AML with NUP98 fusions is characterized by high expression of HOXA and MEIS1 genes and is associated with poor clinical outcome. NUP98 fusion proteins are recruited to their target genes by the mixed lineage leukemia (MLL) complex, which involves a direct interaction between MLL and Menin. Here, we show that therapeutic targeting of the Menin–MLL interaction inhibits the propagation of NUP98-rearrranged AML both ex vivo and in vivo. Treatment of primary AML cells with the Menin inhibitor revumenib (SNDX-5613) impairs proliferation and clonogenicity ex vivo in long-term coculture and drives myeloid differentiation. These phenotypic effects are associated with global gene expression changes in primary AML samples that involve the downregulation of many critical NUP98 fusion protein-target genes, such as MEIS1 and CDK6. In addition, Menin inhibition reduces the expression of both wild-type FLT3 and mutated FLT3-ITD, and in combination with FLT3 inhibitor, suppresses patient-derived NUP98-r AML cells in a synergistic manner. Revumenib treatment blocks leukemic engraftment and prevents leukemia-associated death of immunodeficient mice transplanted with NUP98::NSD1 FLT3-ITD-positive patient-derived AML cells. These results demonstrate that NUP98-rearranged AMLs are highly susceptible to inhibition of the MLL–Menin interaction and suggest the inclusion of AML patients harboring NUP98 fusions into the clinical evaluation of Menin inhibitors

Uncertainty Assessment in Multi-Criteria Sustainability Assessments

How can indicator weights for multi-criteria sustainability assessments be determined based on experts' opinions? How do different opinions affect the results of sustainability assessments

Phase II-like murine trial identifies synergy between dexamethasone and dasatinib in T-cell acute lymphoblastic leukemia

T-cell Acute Lymphoblastic Leukemia (T-ALL) is frequently characterized by glucocorticoid (GC) resistance, which is associated with inferior outcomes, thus highlighting the need for novel therapeutic approaches for GC resistant T-ALL. The pTCR/TCR signaling pathways play a critical role in cell fate decisions during physiological thymocyte development, with an interplay between TCR and glucocorticoid receptor (GR) signaling determining the T-lymphocyte selection process. We performed an shRNA screen in vitro and in vivo in T-ALL cell lines and patient derived xenograft (PDX) samples to identify vulnerabilities in the pTCR/TCR pathway and identified a critical role for the kinase LCK in cell proliferation. LCK knockdown or inhibition with dasatinib (DAS) caused cell cycle arrest. Combination of DAS with dexamethasone (DEX) resulted in significant drug synergy leading to cell death. The efficacy of this drug combination was underscored in a randomized phase II-like murine trial, recapitulating an early phase human clinical trial. T-ALL expansion in immunocompromised mice was significantly impaired using this drug combination, relative to mice receiving control vehicle or single drug treatment, highlighting the immediate clinical relevance of this drug combination for high risk T-ALL patients. Our results thus provide a strategy to improve the efficacy of current chemotherapy platforms and circumvent GC resistance

Quantitative modelling: Key aspects of models

Quantitative modelling: Key aspects of models What can models deliver? Where are their limits

Combining CRISPR-Cas9 and TCR exchange to generate a safe and efficient cord blood-derived T cell product for pediatric relapsed AML

BACKGROUND: Hematopoietic cell transplantation (HCT) is an effective treatment for pediatric patients with high-risk, refractory, or relapsed acute myeloid leukemia (AML). However, a large proportion of transplanted patients eventually die due to relapse. To improve overall survival, we propose a combined strategy based on cord blood (CB)-HCT with the application of AML-specific T cell receptor (TCR)-engineered T cell therapy derived from the same CB graft. METHODS: We produced CB-CD8 + T cells expressing a recombinant TCR (rTCR) against Wilms tumor 1 (WT1) while lacking endogenous TCR (eTCR) expression to avoid mispairing and competition. CRISPR-Cas9 multiplexing was used to target the constant region of the endogenous TCRα ( TRAC) and TCRβ ( TRBC) chains. Next, an optimized method for lentiviral transduction was used to introduce recombinant WT1-TCR. The cytotoxic and migration capacity of the product was evaluated in coculture assays for both cell lines and primary pediatric AML blasts. RESULTS: The gene editing and transduction procedures achieved high efficiency, with up to 95% of cells lacking eTCR and over 70% of T cells expressing rWT1-TCR. WT1-TCR-engineered T cells lacking the expression of their eTCR (eTCR -/- WT1-TCR) showed increased cell surface expression of the rTCR and production of cytotoxic cytokines, such as granzyme A and B, perforin, interferon-γ (IFNγ), and tumor necrosis factor-α (TNFα), on antigen recognition when compared with WT1-TCR-engineered T cells still expressing their eTCR (eTCR +/+ WT1-TCR). CRISPR-Cas9 editing did not affect immunophenotypic characteristics or T cell activation and did not induce increased expression of inhibitory molecules. eTCR -/- WT1-TCR CD8 + CB-T cells showed effective migratory and killing capacity in cocultures with neoplastic cell lines and primary AML blasts, but did not show toxicity toward healthy cells. CONCLUSIONS: In summary, we show the feasibility of developing a potent CB-derived CD8 + T cell product targeting WT1, providing an option for post-transplant allogeneic immune cell therapy or as an off-the-shelf product, to prevent relapse and improve the clinical outcome of children with AML