Design Experience: ein holistischer, multisensorischer und multidimensionaler Ansatz

While product design has sparked a stream of research, practitioners and academics alike are still uncertain as how to more fully capture consumer reactions and how to measure the effective functioning of design. Integrating research on consumer experience with studies of design, this work introduces design experience (DX) as a novel concept, shows how DX affects consumer behavior and develops a DX measurement scale. Four studies and four expert evaluations explore the construct with design professionals and consumers, develop a quantitative measure, and show how DX affects directly and indirextly consumer behavioral outcomes. Using a mixed methods approach Study 1 explores the concept with design professionals, generates items, and tests content validity. Study 2 and the expert evaluations (1-3) develop the DX scale and test content and face validity. Study 3 validates the scale with a consumer sample, corroborates the scale's reliability, establishes its five-dimensional structure, and provides evidence for convergent validity. Study 4 then tests the scale's discriminant and predictive validity and provides evidence for the process mechanism underlying DX's predictive power by testing direct effects, by identifying pleasure as a mediator and by highlighting individual differences as a boundary condition. Finally, the fourth expert evaluation revisits the industry professionals to further validate the scale.Trotz der hohen Popularität von Produktdesign in der Forschung, sind sich Wirtschaft und Wissenschaft immer noch unklar darüber, wie Konsumentenreaktion erfasst und deren tatsächlicher Ablauf und Mechanismus gemessen werden können. Basierend auf einer Kombination von Forschungsergebnissen aus den Bereichen Consumer Experience und Design, entwickelt die vorliegende Arbeit das neuartige Konzept Design Experience (DX), zeigt wie DX Konsumentenverhalten beeinflusst und entwickelt die DX Messskala. Vier Studien und vier Expertenbewertungen erkunden in einem mixed-method Ansatz das Konstrukt mit professionellen Designern und Konsumenten, entwickeln ein quantitatives Messinstrument und zeigen den direkten und indirekten Einfluss von DX auf das Konsumentenverhalten. Studie 1 untersucht in Experteninterviews das Konzept mit professionellen Designern, generiert Items und testet Inhalts- und Augenscheinvalidität. Studie 2 und die Expertenbewertungen (1-3) entwickeln die Skala und testen deren Inhalts- und Augenscheinvalidität. Studie 3 validiert die Skala mit einem Konsumentensample, bestätigt ihre Reliabilität und manifestiert die 5-dimensionale Struktur von DX und liefert Beweise für die Konvergenzvalidität. Studie 4 testet die Diskriminanzvalidität sowie die Vorhersagekraft, liefert Indizien für die Funktionsweise der Vorhersagekraft von DX, indem direkte Effekte getestet werden, Affekt als Mediator identifiziert wird und individuelle Unterschiede als einschränkende Faktoren hervorgehoben werden. Die 4. Expertenbewertung vervollständigt das Vorgehen mittels abschließender Validierung durch aktive professionelle Designer

Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine and Vaccinia Virus

Colorectal carcinoma (CRC) is today’s third most common cause of cancer related death worldwide. Even though considerable advances in prevention, early detection and treatment options have been obtained in the last decades, metastatic CRC still implies very poor prognosis. Starvation (Fasting) has been shown to sensitize tumor cells to chemotherapy whilst protecting normal cells at the same time [Differential Stress Resistance, (DSR)]. Upregulation of pro-survival and proliferation pathways due to various mutations prevents cancer cells from responding to external growth factors. Consequently, malignant cells, unable to adapt to extreme environmental conditions such as absence of nutrients, are becoming more vulnerable to stress. Normal cells, in contrast, enter a standby mode in response to starvation and are getting more protected. The ability of oncolytic virotherapeutics (OVs) to selectively infect, replicate in and lyse cancer cells outlines a promising approach in cancer therapy. However, combinatorial concepts seem to be needed to achieve sustained anti-cancer effects, such as combination of OVs with chemotherapy or new immunomodulatory drugs. We hypothesized that starvation would increase the oncolytic potential of OVs in CRC cell lines and protect normal colon cells against virus-mediated cell lysis. Three different human colon carcinoma cell lines (HT-29, HCT-15 and HCT-116) as well as two human normal colon cell lines (CCD-18 Co and CCD-841 CoN) were subjected to various starvation regimes in glucose and/or serum restricted cell culture medium and infected with two state-of-the-art OVs [i.e., measles vaccine virus (MeV) and vaccinia virus (GLV-1h68)]. Fasting regimes applied were either short-term starvation (24 h pre-infection) or long-term starvation (24 h pre- and 96 h post-infection). We used cell viability assays to determine the cell killing capabilities of i) virotherapy, ii) starvation, and iii) the combination of these two. Virus growth curves were generated to assess the replication of MeV in starved and non-starved HT29 cells. As a result, starvation retarded cell growth in all cell lines in a time and concentration dependent manner. Infection of starved cancer cells exhibited additional oncolytic potential of virotherapy plus starvation for most combinations, indicating that virus-mediated oncolysis is sufficiently working under starvation conditions. Remarkably, long-term standard glucose, low-serum starvation potentiated the efficacy of MeV-mediated cell killing in HT-29 cancer cells, whereas it was decreased in normal colon cells CCD-18 Co and CCD-841 CoN. Interestingly, viral replication of MeV in HT-29 was decreased in long-term starved cells, but was increased after short-term low-glucose, low-serum starvation. We speculate that particular nutrient signaling pathways such as the PI3K/ Akt/ mTOR pathway are modified upon fasting depending on specific mutations in cancer cells resulting in a differential response of distinct CRC cells to OVs. In conclusion, starvation based virotherapy could enhance the oncolytic effect on CRC in future anti-cancer therapy while protecting normal tissues from side effects

Beiträge zur strukturchemischen Untersuchung von Wasserstoffbrückenbindungen in ammoniakhaltigen Aziden, Amiden und Ammoniumsalzen

Im Rahmen dieser Arbeit wurden aus flüssigem Ammoniak folgende Verbindungen isoliert und strukturchemisch charakterisiert: Rubidiumamid-Ammoniakat (3/2) Natriumazid-Ammoniakat (1/5) Kalium(18-krone-6)azid-Ammoniakat (1/1) Rubidium(18-krone-6)azid-Ammoniakat (1/3) Hexaamminkupfer(II)-azid-Ammoniakat (1/4) Hexaamminnickel(II)-azid-Ammoniakat (1/4) Hexaammincobalt(II)-azid-Ammoniakat (1/4) Hexaammincadmium(II)-azid-Ammoniakat (1/4) Hexaamminkupfer(II)-dicyanamid-Ammoniakat (1/2) Hexaammincadmium(II)-dicyanamid-Ammoniakat (1/2) Bis(ammonium)acetylendicarboxylat-Ammoniakat (1/6) Ammoniumpentanoat-Ammoniakat (1/1) Ammoniumhexanoat-Ammoniakat (1/1) Ammoniumbenzoat-Ammoniakat (1/3) Ammoniumphthalat-Ammoniakat (1/2) Ammoniumisophthalat-Ammoniakat (1/6) Ammoniumterephthalat- Ammoniakat (1/4) Dabei wurden die enthaltenen Wasserstoffbrückenbindungen, insbesondere N-H...N-Wasserstoffbrückenbindungen statistisch erfasst und diskutiert

Clinical outcome of Mantle Cell Lymphoma patients with high-risk disease (high-risk MIPI-c or high p53 expression)

Currently, treatment allocation of patients with Mantle Cell Lymphoma (MCL) is mainly based on age and medical fitness. The combined MCL International Prognostic Index (MIPI-c) allows to predict prognosis using clinical factors (MIPI) and the Ki-67 index. However, high p53 expression as surrogate for TP53 alterations has demonstrated to be an independent predictor for poor outcome. We aimed to define a clear high-risk group based on the combination of MIPI, Ki-67 and p53 expression/TP53 alteration. A total of 684 patients from the prospective European MCL-Younger and MCL-Elderly trials were evaluable. The classification of high-risk disease (HRD) as high-risk MIPI-c or p53 expression &gt;50% versus low-risk disease (LRD) as low, low-intermediate or high-intermediate MIPI-c and p53 expression ≤50% allowed to characterize two distinct groups with highly divergent outcome. Patients with HRD had significantly shorter median failure-free survival (FFS) (1.1 vs. 5.6 years, p &lt; 0.0001) and overall survival (OS) (2.2 vs. 13.2 years, p &lt; 0.0001) compared to those with LRD. These major differences were confirmed in two validation cohorts from the Italian MCL0208 and the Nordic-MCL4 trials. The results suggest that this subset of HRD patients is not sufficiently managed with the current standard treatment and is asking for novel treatment strategies.</p

Patient-centered practice in elderly myeloma patients: an overview and consensus from the European Myeloma Network (EMN)

Multiple myeloma is a disease typical of the elderly, and, because of the increase in life expectancy of the general population, its incidence is expected to grow in the future. Elderly patients represent a particular challenge due to their marked hete rogeneity. Many new and highly effective drugs have been introduced in the last few years, and resu lts from clinical trials are promising. Besides the availability of novel agents, a careful evaluation of elderly patients showed to be a key factor for the success of therapy. A geriatric assessment is a valid strategy to better stratify patients. In particular, different scores are available today to appropriately assess elderly patients and define their fitness/frailty status. The choice of treatm ent – transplantation, triplets, doublets, or reduced- dose therapies including novel agents – should depend on the patient’s fitness status (fit, intermediate-fit or frail). Second-generation no vel agents have also been evaluated as salvage therapy in the elderly, and these new agents certai nly represent a further step forward in the treatment armamentarium for elderly patients with multiple myeloma

Molecular Cytogenetic Profiling Reveals Similarities and Differences Between Localized Nodal and Systemic Follicular Lymphomas

Recently, we have developed novel highly promising gene expression (GE) classifiers discriminating localized nodal (LFL) from systemic follicular lymphoma (SFL) with prognostic impact. However, few data are available in LFL especially concerning hotspot genetic alterations that are associated with the pathogenesis and prognosis of SFL. A total of 144 LFL and 527 SFL, enrolled in prospective clinical trials of the German Low Grade Lymphoma Study Group, were analyzed by fluorescence in situ hybridization to detect deletions in chromosomes 1p, 6q, and 17p as well as BCL2 translocations to determine their impact on clinical outcome of LFL patients. The frequency of chromosomal deletions in 1p and 17p was comparable between LFL and SFL, while 6q deletions and BCL2 translocations more frequently occurred in SFL. A higher proportion of 1p deletions was seen in BCL2-translocation–positive LFL, compared with BCL2-translocation–negative LFL. Deletions in chromosomes 1p, 6q, and 17p predicted clinical outcome of patients with SFL in the entire cohort, while only deletions in chromosome 1p retained its negative prognostic impact in R-CHOP–treated SFL. In contrast, no deletions in one of the investigated genetic loci predicted clinical outcome in LFL. Likewise, the presence or absence of BCL2 translocations had no prognostic impact in LFL. Despite representing a genetic portfolio closely resembling SFL, LFL showed some differences in deletion frequencies. BCL2 translocation and 6q deletion frequency differs between LFL and SFL and might contribute to distinct genetic profiles in LFL and SFL

Zu jeder Aufgabe die richtige Strategie? Zum Stellenwert literarischer Strategien für Aufgaben im kompetenzorientierten Literaturunterricht

Im folgenden Text sollen diese zwei grundlegenden Herausforderungen für den Literaturunterricht fokussiert werden: Einerseits geht es um eine höhere Zielbewusstheit, also darum, dass die Lernenden wissen, welche Ziele sie im Literaturunterricht erreichen sollen und welche Kriterien für das Erreichen dieser Ziele erfüllt werden müssen. Auf der anderen Seite werden Strategien beschrieben, die für die Zielerreichung angewendet werden können und mit denen ein Fortschritt im Lernprozess erreicht werden kann. Theoretische Grundlage für diese Strategien bildet das semiotische Modell literarischer Kompetenz von Schilcher/Pissarek (Hgg.)