What is the role of design-led innovation and design-led prototyping in developing novel business models?

Recently, ‘business model’ and ‘business model innovation’ have gained substantial attention in management literature and practice. However, many firms lack the capability to develop a novel business model to capture the value from new technologies. Existing literature on business model innovation highlights the central role of ‘customer value’. Further, it suggests that firms need to experiment with different business models and engage in ‘trail-and-error’ learning when participating in business model innovation. Trial-and error processes and prototyping with tangible artifacts are a fundamental characteristic of design. This conceptual paper explores the role of design-led innovation in facilitating firms to conceive and prototype novel and meaningful business models. It provides a brief review of the conceptual discussion on business model innovation and highlights the opportunities for linking it with the research stream of design-led innovation. We propose design-led business model innovation as a future research area and highlight the role of design-led prototyping and new types of artifacts and prototypes play within it. We present six propositions in order to outline future research avenues.

Detection of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2(PAI-2) in gingival crevicular fluid from healthy, gingivitis and periodontitis patients

Background: The regulation of plasminogen activation is a key element in controlling proteolytic events in the extracellular matrix. Our previous studies had demonstrated that in inflamed gingival tissues, tissue-type plasminogen activator (t-PA) is significantly increased in the extracellular matrix of the connective tissue and that interleukin 1β (IL-1β) can up regulate the level of t-PA and plasminogen activator inhibitor-2 (PAI-2) synthesis by human gingival fibroblasts. Method: In the present study, the levels of t-PA and PAI-2 in gingival crevicular fluid (GCF) were measured from healthy, gingivitis and periodontitis sites and compared before and after periodontal treatment. Crevicular fluid from106 periodontal sites in 33 patients were collected. 24 sites from 11 periodontitis patients received periodontal treatment after the first sample collection and post-treatment samples were collected 14 days after treatment. All samples were analyzed by enzyme-linked immunosorbent assay (ELISA) for t-PA and PAI-2. Results: The results showed that significantly high levels of t-PA and PAI-2 in GCF were found in the gingivitis and periodontitis sites. Periodontal treatment led to significant decreases of PAI-2, but not t-PA, after 14 days. A significant positive linear correlation was found between t-PA and PAI-2 in GCF (r=0.80, p<0.01). In the healthy group, different sites from within the same subject showed little variation of t-PA and PAI-2 in GCF. However, the gingivitis and periodontitis sites showed large variation. These results suggest a good correlation between t-PA and PAI-2 with the severity of periodontal conditions. Conclusion: This study indicates that t-PA and PAI-2 may play a significant rôle in the periodontal tissue destruction and tissue remodeling and that t-PA and PAI-2 in GCF may be used as clinical markers to evaluate the periodontal diseases and assess treatment.

Effect of lipopolysaccharide from periodontal pathogens on the production of tissue plasminogen activator and plasminogen activator inhibitor 2 by human gingival fibroblasts.

Both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2 (PAI-2) are important proteolysis factors present in inflamed human periodontal tissues. The aim of the present study was to investigate the effect of lipopolysaccharide (LPS) on the synthesis of t-PA and PAI-2 by human gingival fibroblasts (HGF). LPS from different periodontal pathogens including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum were extracted by the hot phenol water method. The levels of t-PA and PAI-2 secreted into the cell culture media were measured by enzyme-linked immunosorbent assays (ELISA). The mRNA for t-PA and PAI-2 were measured by RT-PCR. The results showed t-PA synthesis was increased in response to all types of LPS studied and PAI-2 level was increased by LPS from A. actinomycetemcomitans and F. nucleatum, but not P. gingivalis. When comparing the effects of LPS from non-periodontal bacteria (Escherichia coli and Salmonella enteritidis) with the LPS from periodontal pathogens, we found that the ratio of t-PA to PAI-2 was greater following exposure of the cells to LPS from periodontal pathogens. The highest ratio of t-PA to PAI-2 was found in those cells exposed to LPS from P. gingivalis. These results indicate that LPS derived from periodontal pathogens may cause unbalanced regulation of plasminogen activator and plasminogen activator inhibitor by HGF and such an effect may, in part, contribute to the destruction of periodontal connective tissue through dysregulated pericellular proteolysis.

Wide-field assessment of the human corneal subbasal nerve plexus in diabetic neuropathy using a novel mapping technique

To develop a rapid optimized technique of wide-field imaging of the human corneal subbasal nerve plexus. A dynamic fixation target was developed and, coupled with semiautomated tiling software, a rapid method of capturing and montaging multiple corneal confocal microscopy images was created. To illustrate the utility of this technique, wide-field maps of the subbasal nerve plexus were produced in 2 participants with diabetes, 1 with and 1 without neuropathy. The technique produced montages of the central 3 mm of the subbasal corneal nerve plexus. The maps seem to show a general reduction in the number of nerve fibers and branches in the diabetic participant with neuropathy compared with the individual without neuropathy. This novel technique will allow more routine and widespread use of subbasal nerve plexus mapping in clinical and research situations. The significant reduction in the time to image the corneal subbasal nerve plexus should expedite studies of larger groups of diabetic patients and those with other conditions affecting nerve fibers. The inferior whorl and the surrounding areas may show the greatest loss of nerve fibers in individuals with diabetic neuropathy, but this should be further investigated in a larger cohort.

Evaluation of screening tests for predicting older driver performance and safety assessed by an on-road test

A number of tests and test batteries are available for the prediction of older driver safety, but many of these have not been validated against standardized driving outcome measures. The aim of this study was to evaluate a series of previously described screening tests in terms of their ability to predict the potential for safe and unsafe driving. Participants included 79 community-dwelling older drivers (M=72.16 years, SD=5.46; range 65-88 years; 57 males and 22 females) who completed a previously validated multi-disciplinary driving assessment, a hazard perception test, a hazard change detection test and a battery of vision and cognitive tests. Participants also completed a standardized on-road driving assessment. The multi-disciplinary test battery had the highest predictive ability with a sensitivity of 80% and a specificity of 73%, followed by the hazard perception test which demonstrated a sensitivity of 75% and a specificity of 61%. These findings suggest that a relatively simple and practical battery of tests from a range of domains has the capacity to predict safe and unsafe driving in older adults.

High level protein expression in plants through the use of a novel autonomously replicating geminivirus shuttle vector

We constructed a novel autonomously replicating gene expression shuttle vector, with the aim of developing a system for transiently expressing proteins at levels useful for commercial production of vaccines and other proteins in plants. The vector, pRIC, is based on the mild strain of the geminivirus Bean yellow dwarf virus (BeYDV-m) and is replicationally released into plant cells from a recombinant Agrobacterium tumefaciens Ti plasmid. pRIC differs from most other geminivirus-based vectors in that the BeYDV replication-associated elements were included in cis rather than from a co-transfected plasmid, while the BeYDV capsid protein (CP) and movement protein (MP) genes were replaced by an antigen encoding transgene expression cassette derived from the non-replicating A. tumefaciens vector, pTRAc. We tested vector efficacy in Nicotiana benthamiana by comparing transient cytoplasmic expression between pRIC and pTRAc constructs encoding either enhanced green fluorescent protein (EGFP) or the subunit vaccine antigens, human papillomavirus subtype 16 (HPV-16) major CP L1 and human immunodeficiency virus subtype C p24 antigen. The pRIC constructs were amplified in planta by up to two orders of magnitude by replication, while 50% more HPV-16 L1 and three- to seven-fold more EGFP and HIV-1 p24 were expressed from pRIC than from pTRAc. Vector replication was shown to be correlated with increased protein expression. We anticipate that this new high-yielding plant expression vector will contribute towards the development of a viable plant production platform for vaccine candidates and other pharmaceuticals. © 2009 Blackwell Publishing Ltd.

Increased expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product P16INK4A in ovarian cancer is associated with progression and unfavourable prognosis

Paraffin sections from 190 epithelial ovarian tumours, including 159 malignant and 31 benign epithelial tumours, were analysed immunohistochemically for expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product p16INK4A (p16). Most benign tumours showed no p16 expression in the tumour cells, whereas only 11% of malignant cancers were p16 negative. A high proportion of p16-positive tumour cells was associated with advanced stage and grade, and with poor prognosis in cancer patients. For FIGO stage 1 tumours, a high proportion of p16-positive tumour cells was associated with poorer survival, suggesting that accumulation of p16 is an early event of ovarian tumorigenesis. In contrast to tumour cells, high expression of p16 in the surrounding stromal cells was not associated with the stage and grade, but was associated with longer survival. When all parameters were combined in multivariate analysis, high p16 expression in stromal cells was not an independent predictor for survival, indicating that low p16 expression in stromal cells is associated with other markers of tumour progression. High expression of p16 survival in the stromal cells of tumours from long-term survivors suggests that tumour growth is limited to some extent by factors associated with p16 expression in the matrix.

Effect of a novel compound from Lycopodium obscurum L. on osteogenic activity of osteoblasts in vitro

We investigated the potential of an extract of Lycopodium obscurum L.; stigmastane-3-oxo-21-oic acid (SA), to enhance osteogensis of mouse osteoblastic MC3T3-E1 cells. SA at a concentration of 16 µM was found to have no significant effect upon the viability of the cells, thus concentrations of 8 µM and 16 µM of SA were used in all further experiments. Both concentrations of SA had an inhibitory affect upon alkaline phosphatase activity (ALP) after 8 days incubation, however, after 16 days activity was restored to control levels. However Alizarin red S staining showed increased levels of mineralization for both concentrations after 16 days culture. Real time PCR showed inhibition of genes Runx2 and Osterix genes responsible for the up-regulation of ALP. However early time point (8 days) up-regulation of bone matrix mineralization genes OPN and OCN, and late time point (16 days) up-regulation of both Jun-D and Fra-2 mRNA expression was significantly enhanced. These results suggest a potential me-chanism of SA in enhancing bone fracture healing is through the up-regulating bone matrix minera-lization.

Bodyweight and other correlates of symptom detected breast cancers in a population offered screening

Objective: To determine factors associated with symptom detected breast cancers in a population offered screening. Methods We interviewed 1,459 Australian women aged 40–69, 946 with symptom detected and 513 with mammogram detected invasive breast cancers ≥1.1 cm in diameter, about their personal, mammogram and breast histories before diagnosis and reviewed medical records for tumour characteristics and mammogram dates, calculating ORs and 95% confidence intervals (CIs) for symptom- vs mammogram-detected cancers in logistic regression models. Results: Lack of regular mammograms (<2 mammograms in the 4.5 years before diagnosis) was the strongest correlate of symptom detected breast cancer (OR=3.04 for irregular or no mammograms). In women who had regular mammograms (≥2 mammograms in the 4.5 years before diagnosis), the independent correlates of symptom detected cancers were low BMI (OR <25kg/m2 vs ≥30kg/m2=2.18, 95% CI 1.23-3.84; p=0.008), increased breast density (available in 498 women) (OR highest quarter vs lowest =3.50, 95% CI 1.76-6.97; ptrend=0.004), high grade cancer and a larger cancer (each p<0.01). In women who did not have regular mammograms, the independent correlates were age <50 years, a first cancer and a ≥2cm cancer. Smoking appeared to modify the association of symptom detected cancer with low BMI (higher ORs for low BMI in current smokers) and estrogen receptor (ER) status (higher ORs for low BMI in ER− cancers). Conclusion: Women with low BMI may benefit from a tailored approach to breast cancer detection, particularly if they smoke.

Lineage-specific biomarkers predict response to FGFR inhibition

In this issue of Cancer Discovery, Guagnano and colleagues use a large and diverse annotated collection of cancer cell lines, the Cancer Cell Line Encyclopedia, to correlate whole-genome expression and genomic alteration datasets with cell line sensitivity data to the novel pan-fibroblast growth factor receptor (FGFR) inhibitor NVP-BGJ398. Their findings underscore not only the preclinical use of such cell line panels in identifying predictive biomarkers, but also the emergence of the FGFRs as valid therapeutic targets, across an increasingly broad range of malignancies.

A novel DRD2 single-nucleotide polymorphism associated with schizophrenia predicts age of onset : HapMap tag-single-nucleotide polymorphism analysis

Background: Dopamine D2 receptor (DRD2) is thought to be critical in regulating the dopaminergic pathway in the brain which is known to be important in the aetiology of schizophrenia. It is therefore not surprising that most antipsychotic medication acts on the Dopamine D2 receptor. DRD2 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and DRD2 polymorphisms have been associated with reduced brain expression. We have previously identified a genetic variant in DRD2, rs6277 to be strongly implicated in schizophrenia susceptibility. Methods: To identity new associations in the DRD2 gene with disease status and clinical severity, we genotyped seven single nucleotide polymorphisms (SNPs) in DRD2 using a multiplex mass spectrometry method. SNPs were chosen using a haplotype block-based gene-tagging approach so the entire DRD2 gene was represented. Results: One polymorphism rs2734839 was found to be significantly associated with schizophrenia as well as late onset age. Individuals carrying the genetic variation were more than twice as likely to have schizophrenia compared to controls. Conclusions: Our results suggest that DRD2 genetic variation is a good indicator for schizophrenia risk and may also be used as a predictor age of onset.

Properties of hand-made clay balls used as a novel filter media

Filtration using granular media such as quarried sand, anthracite and granular activated carbon is a well-known technique used in both water and wastewater treatment. A relatively new prefiltration method called pebble matrix filtration (PMF) technology has been proved effective in treating high turbidity water during heavy rain periods that occur in many parts of the world. Sand and pebbles are the principal filter media used in PMF laboratory and pilot field trials conducted in the UK, Papua New Guinea and Serbia. However during first full-scale trials at a water treatment plant in Sri Lanka in 2008, problems were encountered in sourcing the required uniform size and shape of pebbles due to cost, scarcity and Government regulations on pebble dredging. As an alternative to pebbles, hand-made clay pebbles (balls) were fired in a kiln and their performance evaluated for the sustainability of the PMF system. These clay balls within a filter bed are subjected to stresses due to self-weight and overburden, therefore, it is important that clay balls should be able to withstand these stresses in water saturated conditions. In this paper, experimentally determined physical properties including compression failure load (Uniaxial Compressive Strength) and tensile strength at failure (theoretical) of hand-made clay balls are described. Hand-made clay balls fired between the kiln temperatures of 875oC to 960oC gave failure loads of between 3.0 kN and 7.1 kN. In another test when clay balls were fired to 1250oC the failure load was 35.0 kN compared to natural Scottish cobbles with an average failure load of 29.5 kN. The uniaxial compressive strength of clay balls obtained by experiment has been presented in terms of the tensile yield stress of clay balls. Based on the effective stress principle in soil mechanics, a method for the estimation of maximum theoretical load on clay balls used as filter media is proposed and compared with experimental failure loads.

Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer

Ghrelin is a multifunctional hormone, with roles in stimulating appetite and regulating energy balance, insulin secretion and glucose homeostasis. The ghrelin gene locus (GHRL) is highly complex and gives rise to a range of novel transcripts derived from alternative first exons and internally spliced exons. The wild-type transcript encodes a 117 amino acid preprohormone that is processed to yield the 28 amino acid peptide ghrelin. Here, we identified insulin-responsive transcription corresponding to cryptic exons in intron 2 of the human ghrelin gene. A transcript, termed in2c-ghrelin (intron 2-cryptic), was cloned from the testis and the LNCaP prostate cancer cell line. This transcript may encode an 83 AA preproghrelin isoform that codes for the ghrelin, but not obestatin. It is expressed in a limited number of normal tissues and in tumours of the prostate, testis, breast and ovary. Finally, we confirmed that in2c-ghrelin transcript expression, as well as the recently described in1-ghrelin transcript, is significantly upregulated by insulin in cultured prostate cancer cells. Metabolic syndrome and hyperinsulinaemia has been associated with prostate cancer risk and progression. This may be particularly significant after androgen deprivation therapy for prostate cancer, which induces hyperinsulinaemia, and this could contribute to castrate resistant prostate cancer growth. We have previously demonstrated that ghrelin stimulates prostate cancer cell line proliferation in vitro. This study is the first description of insulin regulation of a ghrelin transcript in cancer, and should provide further impetus for studies into the expression, regulation and function of ghrelin gene products.