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Selected Abstracts


Antibody response to influenza infection of mice: different patterns for glycoprotein and nucleocapsid antigens

IMMUNOLOGY, Issue 4 2003
Robert Sealy
Summary Our previous studies of C57BL/6 mice intranasally infected with influenza virus (A/PR8) revealed a spike of virus-specific immunoglobulin A (IgA)-secreting antibody-forming cells (AFC) in the mediastinal lymph node (MLN) 7 days post-infection. Here we show that these AFC are directed only against viral glycoprotein, and not nucleocapsid antigens. The early IgA spike associates with a decline in glycoprotein-specific AFC during week 2 post-infection. In contrast to the glycoprotein-specific AFC, nucleocapsid-specific, IgA-secreting AFC develop gradually in the MLN and persist for more than 3 weeks post-infection. As peripheral lymph node reactions wane, the nucleocapsid-specific AFC appear as long-sustained populations in the bone marrow. Microanatomical examination of the respiratory tract in infected mice shows foci of infection established in the lung 2 days post-infection, from which virus spreads to infect the entire lining of the trachea by day 3. At this time, viral haemagglutinin can be seen within the MLN, probably on projections from infected dendritic cells. This feature disappears within a day, though viral antigen expression continues to spread throughout the respiratory tract. Total IgA- and IgG-secreting AFC appear histologically in large numbers during the first week post-infection, significantly preceding the appearance of germinal centres (revealed by peanut agglutinin staining in week 2). To explain these results, we suggest that the initial immunogenic encounter of B cells with viral antigens occurs about 3 days post-infection in the MLN, with antigens transported by dendritic cells from airway mucosa, the only site of viral replication. Viral glycoproteins expressed as integral membrane components on the surface of infected dendritic cells [probably in the absence of cognate T helper (Th) cells] promote members of expanding relevant B-cell clones to undergo an IgA switch and terminal local plasmacytoid differentiation. Anti-glycoprotein specificities are thus selectively depleted from progeny of activated B-cell clones which are channelled to participate in germinal centre formation (perhaps by cognate T helper cells when they become sufficiently frequent). One product of the germinal centre reaction is the long-sustained, bone marrow-resident population, which is accordingly rich in anti-nucleoprotein, but not anti-glycoprotein specificities. Of note, we find that AFC responses toward influenza virus and Sendai virus differ, even though viral replication is limited to the airway mucosa in each case. The response towards Sendai virus exhibits neither the early appearance of anti-glycoprotein AFC expressing IgA in draining lymph nodes, nor the subsequent relative deficit of this specificity from bone marrow AFC populations. [source]


Synthesis and chemical stability of a disulfide bond in a model cyclic pentapeptide: Cyclo(1,4)-Cys-Gly-Phe-Cys-Gly-OH

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2006
Henry T. He
Abstract Many cyclic peptides are formed using a disulfide bond to increase their conformational rigidity; this provides receptor selectivity and increased potency. However, degradation of the disulfide bond in formulation can lead to a loss of structural stability and biological activity of the peptide. Therefore, the objective of this study was to study the stability of peptide 1 (cyclo(1,4)-Cys-Gly-Phe-Cys-Gly-OH). This cyclic peptide was synthesized using Boc strategy via solution-phase peptide synthesis and purified using semi-preparative HPLC. The accelerated stability studies of the cyclic peptide were conducted in buffer solutions at pH 1.0,11.0 with controlled ionic strengths at 70°C. The pH-rate profile shows that the peptide has an optimal stability around pH 3.0 with a V-shape between pH 1.0 and 5.0. Two small plateaus are observed at pH 5.0,7.0 and pH 8.0,10.0, indicating hydrolysis on different ionized forms of the cyclic peptide. One product was observed at acidic pH due to peptide bond hydrolysis at Gly2-Phe3. The number of degradation products increases as the pH increases from neutral to basic, and most of the degradation products at neutral and basic pH are derived from the degradation at the disulfide bond. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2222,2234, 2006 [source]


Biosynthesis of New Indigoid Inhibitors of Protein Kinases Using Recombinant Cytochrome P450 2A6

CHEMISTRY & BIODIVERSITY, Issue 1 2005
Zhongliu-Liu Wu
Glycogen synthase kinase-3 (GSK-3) is a potential drug target for a number of human diseases. Some indigoids have been found to be potent inhibitors of GSK-3, and individual compounds with better activity, specificity, and solubility are desired. In this work, a new disubstituted indigoid generation system was developed with a tryptophanase-deficient Escherichia coli strain as a host to express the human cytochrome P450 2A6 mutant L240C/N297Q, which catalyzes the oxidation of indole to isatin and indoxyl, which in turn react to generate indigoids. Forty-five substituted 1H -indoles from commercial sources were used as substrates in the system, and indigoid mixtures were tested as potential inhibitors of GSK-3. After preliminary screening, cell extracts with high inhibitory activity towards GSK-3,/, were fractionated, and the IC50 values of twelve individual indigoids were measured for GSK-3,/, as well as the protein kinases CDK1/cyclinB and CDK5/p25. Several indigoids, including an indigo, showed stronger inhibition than found in previous work. The most potent towards GSK-3,/,, dimethyl indirubin 5,5,-dicarboxylate (IC50 of 51,nM), was modified by chemical reactions. One product, indirubin 5,5,-dicarboxylic acid 5-methyl ester, inhibited GSK-3,/, with an IC50 of 14,nM and selectivity nearly 40-fold over CDK1 and CDK5. Indirubin-5-5,-dicarbonitrile was also modified to the corresponding 3,-oxime, which had low specificity but showed very high inhibition of all three kinases with IC50 values of 5, 13, and 10,nM towards GSK-3,/,, CDK1, and CDK5, respectively. Thus, this system has the potential to generate new indigoids with therapeutic potential. [source]


Novel Enantioselective Synthesis of Functionalized Pyridylarsanes by a Chiral Palladium Template Promoted Asymmetric Hydroarsanation Reaction

EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 27 2009
Fengli Liu
Abstract The asymmetric hydroarsanation reactions between diphenylarsane and (E)-1-phenyl-3-(pyridin-2-yl)-2-propenone and (E)-1-methyl-3-(pyridin-2-yl)-2-propenoate have been achieved by use of the organopalladium complex containing ortho -metalated (R)-[1-(dimethylamino)ethyl]naphthalene as the chiral reaction template in high regio- and stereoselectivities under mild conditions. Hydroarsanation of (E)-1-phenyl-3-(pyridin-2-yl)-2-propenone with diphenylarsane generated two stereoisomeric products in the ratio of 3:1 as five-membered As,N bidentate chelates on the chiral naphthylamine palladium template. Using the same chiral metal template, the corresponding hydroarsanation reaction with (E)-1-methyl-3-(pyridin-2-yl)-2-propenoate gave only one product as a six-membered As,N bidentate chelate. The naphthylamine auxiliary could be removed chemoselectively by treatment with concentrated hydrochloric acid to form the corresponding optically pure neutral complexes. Subsequent ligands displacement from the palladium using aqueous potassium cyanide generated the optically pure keto- and ester-functionalized chiral pyridylarsane ligands. The absolute configuration and the coordination properties of the pyridylarsanes have been established by single-crystal X-ray analysis.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]


A New Approach to Pyrrolocoumarin Derivatives by Palladium-Catalyzed Reactions: Expedient Construction of Polycyclic Lamellarin Scaffold

ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 11-12 2009
Lei Chen
Abstract A new and efficient protocol for straightforward synthesis of chromeno[3,4- b]pyrrol-4(3H)-one derivatives by palladium-catalyzed sequential coupling/cyclization reactions has been developed. The key strategy relies on creation of pyrrole ring through palladium-catalyzed intramolecular hydroamination of related acetylenic aminocoumarins. The synthetic utility of the obtained chromeno[3,4- b]pyrrol-4(3H)-one product has been demonstrated by the expedient synthesis of polycyclic lamellarin scaffold in four steps. It provides a new entry to synthesis of potentially valuable lamellarin analogues. [source]


Corrosion of Dental Magnet Attachments for Removable Prostheses on Teeth and Implants

JOURNAL OF PROSTHODONTICS, Issue 4 2009
Arne F. Boeckler DMD, Dr Med Dent
Abstract Purpose: For a long time, the use of magnets for the anchorage of dental prostheses failed due to lack of biocompatibility and the magnets' high susceptibility to corrosion in the mouth. These facts make encapsulation of the magnetic alloy with a corrosion-resistant, tight, and functionally firm sealing necessary. Due to different products and analysis methods, it is not feasible to compare the findings for contemporary products with the sparse and rather old test results in the literature. Therefore, the aim of this study was the standardized control and the comparison of the corrosion behavior of modern magnetic attachments for use on teeth and dental implants. Materials and Methods: Thirty-seven components of magnetic attachments on implants and natural teeth from different alloys (NdFeB, SmCo, Ti, CrMoMnTiFe, etc.) as delivered by the manufacturers or fabricated according to their instructions were examined for their corrosion behavior using the statical immersion analysis (ISO 10271:2001). Four specimens of every product with the same design were used. An uncased SmCo magnet served as control. Analyses after 1, 4, 7, and 28 days of the storage in corrosion solution were made. The eluate was examined quantitatively on the alloy components of the respective component with the help of optical emission spectrometry (,g/cm2). The results were compared to the requirements of ISO standard 22674:2006. In addition, existing corrosion products were also defined in the solution after 28 days. The results were analyzed descriptively and statistically to determine possible significant differences (t -test and Mann-Whitney-Wilcoxon rank-sums test; p < 0.05). Results: Dissolved metal ions could be found on all tested products. The release after 1 and 4 days was different for all specimens. In the group of implant abutments, the highest ion release after 7 days was found (all measurements ,g/cm2): Fe (13.94, Magfit-IP-IDN dome type), Pd (1.53, Medical-anchor), Cr (1.32, Magfit-IP-IDN dome type), Ti (1.09, Magfit-IP-IDN abutment), Co (0.81, Medical-anchor), and B (0.6, Magfit-IP-IDN dome type). After 28 days, the analyzed ion release increased irregularly: Fe (173.58, Magfit-IP-IDN dome type), Pd (44.17, Medical-anchor), Cr (2.02, Magfit-IP-IDN dome type), Ti (2.11, Magfit-IP-IDN abutment), Co (26.13, Medical-anchor), B (1.77, Magfit-IP-IDN dome type), and Nd (79.18, Magfit-IP-IDN dome type). In the group of magnetic systems on natural teeth, the highest ion release after 7 days was found for Fe (4.81, Magfit DX 800 keeper), Cr (1.18, Magfit DX 800 keeper), Pd (0.21, Direct System Keeper), Ni (0.18, WR-Magnet S3 small), Co (0.12, Direct System Keeper), and Ti (0.09, Magna Cap , Mini). After 28 days, the analyzed ion release increased non-uniformly: Fe (31.92, Magfit DX 800 Keeper), Cr (6.65, Magfit DX 800 Keeper), Pd (18.19, Direct System Keeper), Ni (0.61, WR-Magnet S3 small), Co (10.94, Direct System Keeper), Ti (0.83, Magna Cap , Mini), and Pd (2.78, EFM Alloy). In contrast, the uncased control magnet showed an exponential release after 7 days of Sm ions (55.06) and Co-ions (86.83), after 28 days of Sm ions (603.91) and Co ions (950.56). The release of corrosion products of all tested products stayed significantly under the limit of 200 ,g/cm2 (ISO 22674:2006). In contrast, the non-encapsulated control magnet exceeded that limit significantly. Conclusion: The analysis of the corrosion behavior of modern magnetic attachments for use on teeth and dental implants according to ISO 10271:2001 showed that metal ions had dissolved on all specimens. In the case of one product, the magnet corroded. For this product, an improvement of the capsulation would be desirable. None of the products reached the limit specified in ISO 22674:2006. All products seem to be suitable for dental application. Further studies in regard to the specific biocompatibility and possible cytotoxic effects on mucosa and tissue would be desirable. [source]


Latest news and product developments

PRESCRIBER, Issue 8 2008
Article first published online: 12 MAY 200
Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source]


The Estimation of a Cusp Model to Describe the Adoption of Word for Windows,

THE JOURNAL OF PRODUCT INNOVATION MANAGEMENT, Issue 1 2004
Rense Lange
This article revisits earlier work in this journal by Paul Herbig (1991) that proposed a catastrophe model of industrial product adoption under certain conditions. Catastrophe models are useful for modeling situations where organizations can exhibit both smooth and abrupt adoption behavior. It extends Herbig's work by focusing on organizations' adoption of new products when network externalities are an important part of the decision process, and it presents an empirical estimation of the model. Network externalities occur when firms do not want to adopt a new innovation or product unless other firms do. The reason is that they do not want to end up with an innovation that ends up not being a standard of some sort. Mistakes of this nature can be costly as the firm must invest twice and loses time relative to competitors who have not made such a mistake. However, when such externalities exist, for example with regard to technological adoptions, then normal diffusion gives way to sudden discontinuous shifts as all firms seemingly act together an move to a new technology. Since, technology is an area where the authors expect network externalities to exist, that is the focus of this article. The specific application is developed from two sets of panel data on the organizational adoptions of Microsoft's (MS) Word for Windows software by organizations that previously were using either Word for DOS or Word for Macintosh (Mac). The theoretical framework for the analysis is based on work in the economics literature on network externalities. However, the organization and new product development catastrophe model comes primarily from Herbig (1991). The article focuses on an area of organizational adoption where relatively little empirical research has been done, namely organizational adoption "for use." Longitudinal data provided by Techtel Corporation is used to develop the estimations. Results of the empirical analysis are consistent with the theoretical framework suggested in Herbig's article and in those found in economics and catastrophe theory literatures. This lends clear support to the idea that organizations will adopt a bandwagon-type behavior when network externalities are present. It further suggests that in such markets, the standard S-shaped diffusion curve is not an appropriate model for examining organizational behavior. From a managerial perspective, it means that buyers and sellers may face nonstandard diffusion curves. Instead of S-shaped curves, the actual curves have a break or rift where sales end, and there is a sudden shift to a new product that is relatively high very early on. Clearly, for new product development (NPD), it suggest that organizations' "for-use" purchases may be similar to regular consumers and may change rapidly from one product to another almost instantly, as in the case of the switch from vinyl records to compact discs (CDs). From an old product seller's viewpoint, the market is here today and gone tomorrow, while for the new seller it is a sudden deluge of sales requests. To put it in more everyday terms, sudden changes in adoption behavior are a September 11-type experience for the market. It is the day the world changes. [source]


Managing platform architectures and manufacturing processes for nonassembled products

THE JOURNAL OF PRODUCT INNOVATION MANAGEMENT, Issue 4 2002
Marc H. Meyer
The article presents methods for defining product platforms and measuring business performance in process intensive industries. We first show how process intensive product platforms can be defined using the products and processes of a film manufacturer. We then present an empirical method for understanding the dynamics of process intensive platform innovation, allocating engineering and sales data to specific platform and product development efforts within a product family. We applied this method to a major product line of a materials manufacturer. We gathered ten years of engineering and manufacturing cost data and allocated these to successive platforms and products, and then generated R&D performance measures. These data show the dynamic of heavy capital spending relative to product engineering as one might expect in a process intensive industries. The data also show how derivative products can be leveraged from underlying product platforms and processes for nonassembled products. Embedded within these data are strategies for creating reusable subsystems (comprising components, materials, etc.) and common production processes. Hard data on the degree to which subsystems and processes are shared across different products frequently are typically not maintained by corporations for the duration needed to understand the dynamics of evolving product families. For this reason, we developed and applied a second method to assess the degree of reuse of subsystems and processes. This method asks engineering managers to provide subjective ratings on an ordinal scale regarding the use of technology and processes from one product to the next in a cumulative manner. We find that high levels of reuse generally indicate that a product family was developed with a platform discipline. We applied this measure of platform intensity to two product lines of integrated circuits from another large manufacturer. We used this method to gather approximately ten years of information for each product family. Upon analysis, one product family showed substantial platform discipline, emphasizing a common architecture and processes across specific products within the product line. The other product family was developed with significantly less sharing and reuse of architecture, components, and processes. We then found that the platform centric product family outperformed the latter along a number of performance dimensions over the course of the decade under examination. [source]


Biorefinery systems , potential contributors to sustainable innovation

BIOFUELS, BIOPRODUCTS AND BIOREFINING, Issue 3 2010
Maria Wellisch
Abstract Sustainable biorefineries have a critical role to play in our common future. The need to provide more goods using renewable resources, combined with advances in science and technology, has provided a receptive environment for biorefinery systems development. Biorefineries offer the promise of using fewer non-renewable resources, reducing CO2 emissions, creating new employment, and spurring innovation using clean and efficient technologies. Lessons are being learned from the establishment of first-generation biofuel operations. The factors that are key to answering the question of biorefinery sustainability include: the type of feedstock, the conversion technologies and their respective conversion and energy efficiencies, the types of products (including coproducts) that are manufactured, and what products are substituted by the bioproducts. The BIOPOL review of eight existing biorefineries indicates that new efficient biorefineries can revitalize existing industries and promote regional development, especially in the R&D area. Establishment can be facilitated if existing facilities are used, if there is at least one product which is immediately marketable, and if supportive policies are in place. Economic, environmental, and social dimensions need to be evaluated in an integrated sustainability assessment. Sustainability principles, criteria, and indicators are emerging for bioenergy, biofuels, and bioproducts. Practical assessment methodologies, including data systems, are critical for both sustainable design and to assure consumers, investors, and governments that they are doing the ,right thing' by purchasing a certain bioproduct. If designed using lifecycle thinking, biorefineries can be profitable, socially responsible, and produce goods with less environmental impact than conventional products , and potentially even be restorative!. Copyright © 2010 Society of Chemical Industry and John Wiley & Sons, Ltd [source]


Who Owns the Product?

THE PHILOSOPHICAL QUARTERLY, Issue 217 2004
Daniel Attas
If persons fully own themselves and can acquire, by unilateral acts, unconditional full property rights to previously unowned natural resources, then by these same principles of property they also own the products of their property and of their labour. But (a) the principles of property are silent on the question of the division of joint products; (b) the market is a form of cooperation in production which makes the total social product a joint product. In the circumstances of an unrestrained fully developed market, therefore, it is not fully determinate what one's product is. Thus the holdings that each person ends up with cannot be justified merely in terms of ownership of products. I offer an explanation of why some may resist this view of the market. [source]