The (2,3)-generation of the special unitary groups of dimension 6

In this paper we give explicit (2,3)-generators of the unitary groups SU_6(q^ 2), for all q. They fit into a uniform sequence of likely (2,3)-generators for all n>= 6

Notch ligand Delta-like 1 as a novel molecular target in childhood neuroblastoma

Abstract Background Neuroblastoma is the most common extracranial solid malignancy in childhood, responsible for 15% of all pediatric cancer deaths. It is an heterogeneous disease that does not always respond to classical therapy; so the identification of new and specific molecular targets to improve existing therapy is needed. We have previously demonstrated the involvement of the Notch pathway in the onset and progression of neuroblastoma. In this study we further investigated the role of Notch signaling and identified Delta-like 1 (DLL1) as a novel molecular target in neuroblastoma cells with a high degree of MYCN amplification, which is a major oncogenic driver in neuroblastoma. The possibility to act on DLL1 expression levels by using microRNAs (miRNAs) was assessed. Methods DLL1 mRNA and protein expression levels were measured in three different neuroblastoma cell lines using quantitative real-time PCR and Western Blot analysis, respectively. Activation of the Notch pathway as a result of increased levels of DLL1 was analyzed by Immunofluorescence and Western Blot methods. In silico tools revealed the possibility to act on DLL1 expression levels with miRNAs, in particular with the miRNA-34 family. Neuroblastoma cells were transfected with miRNA-34 family members, and the effect of miRNAs transfection on DLL1 mRNA expression levels, on cell differentiation, proliferation and apoptosis was measured. Results In this study, the DLL1 ligand was identified as the Notch pathway component highly expressed in neuroblastoma cells with MYCN amplification. In silico analysis demonstrated that DLL1 is one of the targets of miRNA-34 family members that maps on chromosome regions that are frequently deregulated or deleted in neuroblastoma. We studied the possibility to use miRNAs to target DLL1. Among all miRNA-34 family members, miRNA-34b is able to significantly downregulate DLL1 mRNA expression levels, to arrest cell proliferation and to induce neuronal differentiation in malignant neuroblastoma cells. Conclusions Targeted therapies have emerged as new strategies for cancer treatment. This study identified the Notch ligand DLL1 as a novel and attractive molecular target in childhood neuroblastoma and its results could help to devise a targeted therapy using miRNAs

Changing Style in Style-Changing Industries: The Role of Critics as Gatekeepers in High-End Fashion

Mastering aesthetics is a precious source of competitive advantage in creative industries. In fashion, innovation is reflected by how and how much styles change. Elite designers claim to be the only endogenous force shaping fashion innovation season by season. Yet, each season, fashion critics vet the new collections these designers introduce, assessing what is original as opposed toreworked and uninspired, in this way playing a fundamental role as gatekeepers in setting taste within the industry. In this research, we document how stylistic innovation, vis-`a-vis the styles premier design houses introduced each season, is impacted, among the others, by the specific exogenous force of critics’ assessments of designers’ past work. Our data, which include 61 measures detailing the styles introduced by 38 prestigious Italian and French design houses over a nine-year period, suggest designers move further away from styles reviewed less favourably while adhering more closely to styles reviewed more positively. Additionally, the styles a designer introduces are shown to depend on critical assessments of competing designers’ styles, revealing how design houses attend to each other’s work. This work documents the strong correlation between style dynamics and critics’ feedback. It also has important implications for any company trying to find a balance between independence and conformity in setting its own unique positioning into the market

Conformational altered p53 affects neuronal function: relevance for the response to toxic insult and growth-associated protein 43 expression

The role of p53 in neurodegenerative diseases is essentially associated with neuronal death. Recently an alternative point of view is emerging, as altered p53 conformation and impaired protein function have been found in fibroblasts and blood cells derived from Alzheimer's disease patients. Here, using stable transfected SH-SY5Y cells overexpressing APP751wt (SY5Y-APP) we demonstrated that the expression of an unfolded p53 conformation compromised neuronal functionality. In particular, these cells showed (i) augmented expression of amyloid precursor protein (APP) and its metabolites, including the C-terminal fragments C99 and C83 and β-amyloid peptide (ii) high levels of oxidative markers, such as 4-hydroxy-2-nonenal Michael-adducts and 3-nitro-tyrosine and (iii) altered p53 conformation, mainly due to nitration of its tyrosine residues. The consequences of high-unfolded p53 expression resulted in loss of p53 pro-apoptotic activity, and reduction of growth-associated protein 43 (GAP-43) mRNA and protein levels. The role of unfolded p53 in cell death resistance and lack of GAP-43 transcription was demonstrated by ZnCl(2) treatment. Zinc supplementation reverted p53 wild-type tertiary structure, increased cells sensitivity to acute cytotoxic injury and GAP-43 levels in SY5Y-APP clone

Conformational Altered p53 as an Early Marker of Oxidative Stress in Alzheimer's Disease

In order to study oxidative stress in peripheral cells of Alzheimer's disease (AD) patients, immortalized lymphocytes derived from two peculiar cohorts of patients, referring to early onset AD (EOSAD) and subjects harboured AD related mutation (ADmut), were used. Oxidative stress was evaluated measuring i) the typical oxidative markers, such as HNE Michel adducts, 3 Nitro-Tyrosine residues and protein carbonyl on protein extracts, ii) and the antioxidant capacity, following the enzymatic kinetic of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GRD). We found that the signs of oxidative stress, measured as oxidative marker levels, were evident only in ADmut but not in EOSAD patients. However, oxidative imbalance in EOSAD as well as ADmut lymphocytes was underlined by a reduced SOD activity and GRD activity in both pathological groups in comparison with cells derived from healthy subjects. Furthermore, a redox modulated p53 protein was found conformational altered in both EOSAD and ADmut B lymphocytes in comparison with control cells. This conformational altered p53 isoform, named “unfolded p53”, was recognized by the use of two specific conformational anti-p53 antibodies. Immunoprecipitation experiments, performed with the monoclonal antibodies PAb1620 (that recognizes p53wt) and PAb240 (that is direct towards unfolded p53), and followed by the immunoblotting with anti-4-hydroxynonenal (HNE) and anti- 3-nitrotyrosine (3NT) antibodies, showed a preferential increase of nitrated tyrosine residues in unfolded p53 isoform comparing to p53 wt protein, in both ADmut and EOSAD. In addition, a correlation between unfolded p53 and SOD activity was further found. Thus this study suggests that ROS/RNS contributed to change of p53 tertiary structure and that unfolded p53 can be considered as an early marker of oxidative imbalance in these patients

Keep them alive! Design and Evaluation of the “Community Fostering Reference Model”

Firms host online communities for commercial purposes, for example in order to integrate customers into ideation for new product development. The success of these firm-hosted online communities depends entirely on the cooperation of a high number of customers that constantly produce valuable knowledge for firms. However, in practice, the majority of successfully implemented communities suffers from stagnation and even a decrease of member activities over time. Literature provides numerous guidelines on how to build and launch these online communities. While these models describe the initial steps of acquiring and activating a community base from scratch very well and explicitly, they neglect continuous member activation and acquistion after a successful launch. Against this background, the authors propose the Community Fostering Reference Model (CoFoRM), which represents a set of general procedures and instruments to continuously foster member activity. In this paper, the authors present the theory-driven design as well as the evaluation of the CoFoRM in a practical use setting. The evaluation results reveal that the CoFoRM represents a valuable instrument in the daily working routine of community managers, since it efficiently helps activating community members especially in the late phases of a community’s LifeCycle

Customization in luxury brands: can Valentino get personal?

Luxury brands have started to offer consumers the opportunity to customize their exclusive products by making certain aesthetic decisions, such as the color, fabric, or cut of their products. A robust finding in the marketing literature is that consumers place a greater value on customized than on standard products because these unique products better fit and communicate their tastes, preferences, and identity. However, the majority of focal products in these studies fall outside the luxury segment. The authors demonstrate that consumers’ customization preferences differ between mainstream and luxury brands. In the luxury segment, consumers pay a premium for the designer’s expertise and the status that it can convey. As such, the consumers’ desire for self-expression can potentially erode the product’s signaling value. Through a series of four experiments, the authors demonstrate that luxury brands can benefit from customization but they can also take customization too far. Their findings suggest that brand managers should allow consumers to make fewer design decisions for luxury versus mainstream brands to preserve the signal value created by the designer

The effect of critical evaluation on stylistic innovation: debunking the myth of designer as dictator

Mastering aesthetics is a precious source of competitive advantage in creative industries. In fashion, innovation is reflected by how and how much styles change. Elite designers claim to be the only endogenous force shaping fashion innovation season by season. Yet, each season, fashion critics vet the new collections these designers introduce, assessing what is original as opposed to reworked and uninspired, in this way playing a fundamental role as gatekeepers in setting taste within the industry. In this research, we document how stylistic innovation, vis-à-vis the styles premier design houses introduced each season, is impacted, among the others, by the specific exogenous force of critics’ assessments of designers’ past work. Our data, which include 61 measures detailing the styles introduced by 38 prestigious Italian and French design houses over a nine-year period, suggest designers move further away from styles reviewed less favorably while adhering more closely to styles reviewed more positively. Additionally, the styles a designer introduces are shown to depend on critical assessments of competing designers’ styles, revealing how design houses attend to each other’s work. This work documents the strong correlation between style dynamics and critics’ feedback. It also has important implications for any company trying to find a balance between independence and conformity in setting its own unique positioning into the market