Probabilistic subgroup identification using Bayesian finite mixture modelling : a case study in Parkinson’s disease phenotype identification

This article explores the use of probabilistic classification, namely finite mixture modelling, for identification of complex disease phenotypes, given cross-sectional data. In particular, if focuses on posterior probabilities of subgroup membership, a standard output of finite mixture modelling, and how the quantification of uncertainty in these probabilities can lead to more detailed analyses. Using a Bayesian approach, we describe two practical uses of this uncertainty: (i) as a means of describing a person’s membership to a single or multiple latent subgroups and (ii) as a means of describing identified subgroups by patient-centred covariates not included in model estimation. These proposed uses are demonstrated on a case study in Parkinson’s disease (PD), where latent subgroups are identified using multiple symptoms from the Unified Parkinson’s Disease Rating Scale (UPDRS).

Profluorescent nitroxides as sensitive probes of oxidative change and free radical reactions

This paper presents a review on the use of tethered nitroxide–fluorophore molecules as probes of oxidative change and free radical generation and reaction. The proximity of the nitroxide free radical to the fluorophore suppresses the normal fluorescence emission process. Nitroxide free radical scavenging, metabolism or redox chemistry return the system to its natural fluorescent state and so these tethered nitroxide–fluorophore molecules are described as being profluorescent. A survey of profluorescent nitroxides found in the literature is provided as well as background on the mechanism of action and applications of these compounds as fluorometric probes within the fields of biological, materials and environmental sciences.

Living characteristics of the free-radical ring-closing polymerization of diallyldimethylammonium chloride

In this communication we provide the most recent results on RAFT-mediated ring-closing polymerization of diallyldimethylammonium chloride (DADMAC). The polymerization was carried out in aqueous solution employing 2,2′-azobis(2-methylpropionamidine)-dihydrochloride as the free radical initiator and trithiocarbonate RAFT agent (2-{[(dodecylsulfanyl)carbonothioyl sulfanyl]}propanoic acid, DoPAT) as the controlling RAFT agent. The results show that – while the system is not as completely controlled as previously described – it is nevertheless possible to mediate the polymerization of DADMAC and impart some living characteristics onto the system. The initial study on the RAFT-mediated polymerization of DADMAC may have overestimated the degree of livingness within this reaction. However, it is possible – at low conversions – for some living characteristics to be observed, as the evolution of molecular weight with conversion is linear. In addition, polymers with a reasonably narrow polydispersity can be isolated.

Is globalisation an enabler of radical innovation in Toyota?

Prior evidence from the fields of innovation management and supplier relations predicts that Japanese firms should be naturally disadvantaged in developing and deploying radical innovations. But this conclusion is inconsistent with recent developments in the automotive industry. This paper presents secondary case study data focusing on fuel cell powered vehicles and hybrid cars to show that Toyota, one of Japan's largest and most influential corporations, is capable of developing radically new technologies, and is in several respects better at this sort of innovation than the rest of the global automotive industry.

What the hare can teach the tortoise about make-buy strategies for radical innovations

Purpose of this paper – The purpose of this investigation is to help establish: whether or not strong relationships between suppliers and customers improve performance; and if prescriptive frameworks on outsourcing radical innovations are dependent on industry clockspeed. Design/methodology/approach – A survey of UK-based manufacturers, followed by a statistical analysis. Findings – Long-term supplier links seem not to play a role in the development of radical innovations. Moreover, industry clockspeed has no significant bearing on the success or failure of any outsourcing strategy for radically new technologies. Research limitations/implications – Literature about outsourcing in the face of radical innovation can be more confidently applied to industries of all clockspeeds. Practical implications – Prescriptions for fast clockspeed industries should be applied more broadly: all industries should maintain a high degree of vertical integration in the early days of a radical innovation. Originality/value – Prior papers had explored whether or not a company should outsource radical innovations, but none had determined if this is equally true for slow industries and fast ones. Therein lies the original contribution of this paper.

Outsourcing strategies for radical innovations: does industry clockspeed make a difference?

Purpose – To determine whether or not clockspeed is an important variable in outsourcing strategies throughout the development of radical innovations. Design/methodology/approach – An internet-based survey of manufacturing firms from all over the world. Findings – An industry's clockspeed does not play a significant role in the success or failure of a particular outsourcing strategy for a radical innovation. Research limitations/implications – Conclusions from earlier research in this area are not necessarily industry-specific. Practical implications – Lessons learned via previous investigations about the computer industry need not be confined to that sector. Vertical integration may be a more robust outsourcing strategy when developing a radical innovation in industries of all clockspeeds. Originality/value – Previous research efforts in this field focused on a single technology jump, but this approach may have overlooked a potentially important variable: industry clockspeed. Thus, this investigation explores whether clockspeed is an important factor.

Designing radical business model innovation : a case study

“The process of innovation is often seen as being very linear, with research results, new technologies or user insights being channelled, often prematurely, into specific products and process” (Kyffin and Gardien 2009). It is precisely this perception of innovation-as-linear-process which this paper seeks to challenge. While there are many current theories and much contemporary literature available which discuss the management and catalysts of innovation, what is missing are examples of how innovation occurs from the application of these theories and literature (Wrigley & Bucolo 2010). This paper addresses both this gap and perceptions of the viability of linear innovation by presenting a case study for the commercialisation of a core technology (a cleantech, semi-portable mass-energy generator posited as a direct competitor to conventional energy provision systems), within an 18-month timeframe by the use of the Design-Led Innovation approach: “a process of creating a sustainable competitive advantage by radically changing the customer value proposition” (Bucolo & Matthews 2011).

Social implications of radical technology adoption within the livestock industry - a design investigation: Innovating disruptive technologies in traditional marketplaces

This thesis presents a design investigation into how traditional technology-orientated markets can use design led innovation (DLI) strategies in order to achieve better market penetration of disruptive products. In a review of the Australian livestock industry, considering historical information and present-day trends, a lack of socio-cultural consideration was identified in the design and implementation of products and systems, previously been taken to market. Hence the adoption of these novel products has been documented as extremely slow. Classical diffusion models have typically been used in order to implement these products. However, this thesis poses that it is through the strategic intent of design led innovation, where heavily technology-orientated markets (such as the Australian livestock industry), can achieve better final adoption rates. By considering a range of external factors (business models, technology and user needs), rather than focusing design efforts solely on the technology, it is argued that using DLI approach will lead to disruptive innovations being made easier to adopt in the Australian livestock industry. This thesis therefore explored two research questions: 1. What are the social inhibitors to the adoption of a new technology in the Australian livestock industry? 2. Can design be used to gain a significant feedback response to the proposed innovation? In order to answer these questions, this thesis used a design led innovation approach to investigate the livestock industry, centring on how design can be used early on in the development of disruptive products being taken to market. This thesis used a three stage data collection programme, combining methods of design thinking, co-design and participatory design. The first study found four key themes to the social barriers of technology adoption; Social attitudes to innovation, Market monitoring, Attitude to 3D imaging and Online processes. These themes were built upon through a design thinking/co-design approach to create three ‘future scenarios’ to be tested in participant workshops. The analysis of the data collection found four key socio-cultural barriers that inhibited the adoption of a disruptive innovation in the Australian livestock industry. These were found to be a lack of Education, a Culture of Innovation, a Lack of Engagement and Communication barriers. This thesis recommends five key areas to be focused upon in the subsequent design of a new product in the Australian livestock industry. These recommendations are made to business and design managers looking to introduce disruptive innovations in this industry. Moreover, the thesis presents three design implications relating to stakeholder attitudes, practical constraints and technological restrictions of innovations within the industry.

When is a spinoff the best way to pursue a radical innovation? Insights from Shell technology ventures

The technology and innovation management literature offers somewhat conflicting evidence with regards to the formation of spinoff companies for radically new technologies. Sometimes spinoffs seem to be a very effective strategy—but not always. An obvious question emerges: under what conditions is a spinoff the best way to pursue a radical technology? This paper sheds light on this question by presenting case study evidence from spinoff firms within the Shell Technology Ventures portfolio. The data point to industry clockspeed as a potentially important variable in the decision to create a spinoff or not.

Alkyl radical geometry controls geminate cage recombination in alkylcobalamins

Abstract: The radical pair that results from photolysis of adenosylcob(II1)alamin (AdoCbl"') undergoes primary geminate recombination with a first-order rate constant of 1 x lo9 s-l. In contrast, methylcob(II1)alamin (CH3Cbl"') and aristeromicylcob(II1)alamin (AriCblII', the carbocyclic analogue of AdoCbl"' in which the ribofuranose ring oxygen has been replaced with a methylene group) does not undergo primary geminate recombination. The ribofwanose group enables a high rate of geminate recombination in the [Ado' Cbl"'] radical pair. This may be due to a stereoelectronic (p-anomeric) effect that maintains a pyramidal geometry at the 5'-carbon of the 5'-deoxyadenosyl radical, or it may be due to hindered rotation about the C4t-C5, bond such that /?-elimination to the olefin is prevented. Recombination in the geminate singlet radical pair is in competition with diffusive escape to form a solvent-separated radical pair. Hyperfine coupling from Co" promotes intersystem crossing to the triplet radical pair (Chagovetz, A. M.; Grissom, C. B. J. Am. Chem. SOC. 1993, 115, 12152). Recombination of the [CH3' Cbl"] radical pair is not prevented by a lack of intersystem crossing, as neither unlabeled or I3C-labeled CH3Cbl"' undergoes geminate recombination. There is only a small difference in the rate of diffusive recombination in the solvent cage for AdoCbl"', AriCbl"', and CH3Cbl"' following photolysis: 2.01 x 10" s-l, 2.20 x lo4 s-l, and 1.16 x lo4 s-l. The rate of diffusive recombination is limited by productive collisions and not by radical geometry or intersystem crossing. The CF3' radical that results from photolysis of (trifluoromethyl)cob(III)alamin (CF3Cbl"') maintains its pyramidal geometry and undergoes faster diffusive recombination in the solvent cage at 51 x lo4 s-l. The C-Co bond dissociation enthalpy in AriCbl"' is 37 f 1.4 kcaymol. The profound difference in geminate recombination rates for AdoCbl"' and CH3Cbl"' is consistent with their different biological roles as enzymatic cofactors: AdoCbl"' is an initiator of radical chain chemistry in the active site, whereas CH3Cbl"' is a methyl group donor in an S~2-type process.

A vibrational spectroscopic study of philipsbornite PbAl3(AsO4)2(OH)5⋅H2O-molecular structural implications and relationship to the crandallite subgroup arsenates

The presence of arsenic in the environment is a hazard. The accumulation of arsenate by a range of cations in the formation of minerals provides a mechanism for the remediation of arsenate contamination. The formation of the crandallite group of minerals provides a mechanism for arsenate accumulation. Among the crandallite minerals are philipsbornite, arsenocrandallite and arsenogoyazite. Raman spectroscopy complimented with infrared spectroscopy has enabled aspects of the structure of philipsbornite to be studied. The Raman spectrum of philipsbornite displays an intense band at around 840 cm−1 attributed to the overlap of the symmetric and antisymmetric stretching modes. Raman bands observed at 325, 336, 347, 357, 376 and 399 cm−1 are assigned to the ν2 (AsO4)3− symmetric bending vibration (E) and to the ν4 bending vibration (F2). The observation of multiple bending modes supports the concept of a reduction in symmetry of the arsenate anion in philipsbornite. Evidence for phosphate in the mineral is provided. By using an empirical formula, hydrogen bond distances for the OH units in philipsbornite of 2.8648 Å, 2.7864 Å, 2.6896 Å cm−1 and 2.6220 were calculated.