Socio-technical paths and crossings in business development

In this paper an evolutionary model of business development is proposed, which links cooperationbetween organizations and their exchanges to path dependence and crossings.While the concept of path dependence restricts action to the exploitation of the existing path, theconcept of crossings emphasizes that within existing structures there are opportunities to take an otherpath. In a case study, over a period of twelve years the business development of a firm and itsevolving network relations are described. To find out if a firm can change is taken path, the conceptsof path dependence and crossings are explored along the cycle of development

How do relationships begin?

In this paper we address the issue ‘How do relationships begin?’ Based on a review of work within theIMP Approach on stage and state models of relationship evolution, we conclude that very littleattention has been paid to beginnings of relationships. We discuss why this might be so, and why theissue deserves more consideration. Based on a case study, we make a first start at discussing how wemay conceptualise and discuss relationship beginnings. Furthermore, we depict a firm’s ‘relationshipinitiation profile’ and suggest that a firm may benefit from examining its profile and the costs andbenefits associated with it. Lastly, we propose issues which may be pursued in further research.Keywords: relationship evolution, stage model, state model, beginning, relationship initiation profile

Simulating a base population in honey bee for molecular genetic studies

<p>Abstract</p> <p>Background</p> <p>Over the past years, reports have indicated that honey bee populations are declining and that infestation by an ecto-parasitic mite (<it>Varroa destructor</it>) is one of the main causes. Selective breeding of resistant bees can help to prevent losses due to the parasite, but it requires that a robust breeding program and genetic evaluation are implemented. Genomic selection has emerged as an important tool in animal breeding programs and simulation studies have shown that it yields more accurate breeding value estimates, higher genetic gain and low rates of inbreeding. Since genomic selection relies on marker data, simulations conducted on a genomic dataset are a pre-requisite before selection can be implemented. Although genomic datasets have been simulated in other species undergoing genetic evaluation, simulation of a genomic dataset specific to the honey bee is required since this species has a distinct genetic and reproductive biology. Our software program was aimed at constructing a base population by simulating a random mating honey bee population. A forward-time population simulation approach was applied since it allows modeling of genetic characteristics and reproductive behavior specific to the honey bee.</p> <p>Results</p> <p>Our software program yielded a genomic dataset for a base population in linkage disequilibrium. In addition, information was obtained on (1) the position of markers on each chromosome, (2) allele frequency, (3) χ² statistics for Hardy-Weinberg equilibrium, (4) a sorted list of markers with a minor allele frequency less than or equal to the input value, (5) average r² values of linkage disequilibrium between all simulated marker loci pair for all generations and (6) average r² value of linkage disequilibrium in the last generation for selected markers with the highest minor allele frequency.</p> <p>Conclusion</p> <p>We developed a software program that takes into account the genetic and reproductive biology specific to the honey bee and that can be used to constitute a genomic dataset compatible with the simulation studies necessary to optimize breeding programs. The source code together with an instruction file is freely accessible at <url>http://msproteomics.org/Research/Misc/honeybeepopulationsimulator.html</url></p

Transient Alteration of Cellular Redox Buffering before Irradiation Triggers Apoptosis in Head and Neck Carcinoma Stem and Non-Stem Cells

Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy owing to intrinsic radioresistance and lack of induction of apoptosis. The major focus of this work was to design a transient glutathione depleting strategy during the course of irradiation of HNSCC in order to overcome their radioresistance associated with redox adaptation. Methodology/Principal Findings: Treatment of SQ20B cells with dimethylfumarate (DMF), a GSH-depleting agent, and L-Buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis 4 h before a 10 Gy irradiation led to the lowering of the endogenous GSH content to less than 10 % of that in control cells and to the triggering of radiation-induced apoptotic cell death. The sequence of biochemical events after GSH depletion and irradiation included ASK-1 followed by JNK activation which resulted in the triggering of the intrinsic apoptotic pathway through Bax translocation to mitochondria. Conclusions: This transient GSH depletion also triggered radiation-induced cell death in SQ20B stem cells, a key event to overcome locoregional recurrence of HNSCC. Finally, our in vivo data highlight the relevance for further clinical trials o

How Should a Small Company Interact in Its Business Network to Sustain Its Exchange Effectiveness?

In this paper we followed the dynamic alignment between networking approaches and business development of a small firm in the printing industry, with the aim of investigating how a small firm embedded in its network can deal with networking paradoxes when developing its business, such that it efficiently maintains its existing business and keeps its flexibility to develop new business. The empirical contribution of this paper lies in the use of a longitudinal case study that enables us to show the intermediary functions of counterparts along the path of a small firm's business and network development. Three mediating functions of counterparts are introduced: the relating, joining and insulating functions. In the study we saw that joining functions of intermediaries were especially used in opportunity creation, while insulating functions of intermediaries were especially used in opportunity exploitation. The case study indicates an evolution into an efficient sales network with an important partner who is not willing to develop new business with Atlas. An explanation for the unwillingness to see the focal firm as a development partner might be found in its network position, reflected in the moderate technological and business integration of their product in customer applications, the weak contact of focal firm with end users, and the insulating function of distributors and original equipment manufacturers, who isolated the focal firm from end users. Managerial implications are drawn and will be investigated in further research

Development of physical fitness performance in young Swiss men from 2006 to 2015

From 1980 to 2000, physical fitness decreased and body mass index (BMI) increased in the population of many industrialised countries. Little is known about these trends after the year 2000. The present study aimed to investigate physical fitness performance, physical activity (PA) behaviour and BMI of young, male Swiss adults between 2006 and 2015. For this purpose, results from the Swiss Armed Forces mandatory recruitment were used. 306,746 male conscripts provided complete fitness test data, mean±SD (range from 5th to 95th‐percentile): 20±1 (18‐21)yrs., 178±7 (168‐189)cm; 74±13 (58‐97)kg, predicted maximal oxygen consumption of 49.9±4.6 (41.8‐56.9)ml*kg−1*min−1 (Conconi test), 125±58 (43‐232)s in trunk muscle strength test (prone bridge), 2.31±0.24 (1.90‐2.66)m in standing long jump, 6.46±0.73 (5.30‐7.70)m in seated shot put (2kg medical‐ball shot) and 45.6±12.2 (29.9‐66.7)s in one‐leg standing test (sum of both legs; eyes closed after 10s and head tilted back after 20s). In the investigated population, 73.8% fulfilled basic PA recommendations, 46.2% were classified as regularly vigorously active. Performances in aerobic endurance and muscle power did not show secular changes over time. However, core stability performance and PA behaviour increased, while balance ability decreased over this ten‐year period. Average BMI increased by 2.0% between 2006 and 2010 and did not change thereafter. Male Swiss adults are at least as physically fit as they were a decade ago. The secular trends of decreasing physical performances and increasing BMI have stopped, self reported sport participation and leisure time PA have been increased in the observed population over the last ten years

Mutations in glycyl-tRNA synthetase impair mitochondrial metabolism in neurons

The nuclear-encoded glycyl-tRNA synthetase gene (GARS) is essential for protein translation in both cytoplasm and mitochondria. In contrast, different genes encode the mitochondrial and cytosolic forms of most other tRNA synthetases. Dominant GARS mutations were described in inherited neuropathies, while recessive mutations cause severe childhoodonset disorders affecting skeletal muscle and heart. The downstream events explaining tissue-specific phenotype-genotype relations remained unclear. We investigated the mitochondrial function of GARS in human cell lines and in the Gars C210R mouse model. Human-induced neuronal progenitor cells (iNPCs) carrying dominant and recessive GARS mutations showed alterations of mitochondrial proteins, which were more prominent in iNPCs with dominant, neuropathy-causing mutations. Although comparative proteomic analysis of iNPCs showed significant changes in mitochondrial respiratory chain complex subunits, assembly genes, Krebs cycle enzymes and transport proteins in both recessive and dominant mutations, proteins involved in fatty acid oxidation were only altered by recessive mutations causing mitochondrial cardiomyopathy. In contrast, significant alterations of the vesicle-associated membrane protein-associated protein B (VAPB) and its downstream pathways such as mitochondrial calciumuptake and autophagy were detected in dominant GARS mutations. The role of VAPB has been supported by similar results in the Gars C210R mice. Our data suggest that altered mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) may be important disease mechanisms leading to neuropathy in this condition

Mutations in glycyl-tRNA synthetase impair mitochondrial metabolism in neurons

The nuclear-encoded glycyl-tRNA synthetase gene (GARS) is essential for protein translation in both cytoplasm and mitochondria. In contrast, different genes encode the mitochondrial and cytosolic forms of most other tRNA synthetases. Dominant GARS mutations were described in inherited neuropathies, while recessive mutations cause severe childhoodonset disorders affecting skeletal muscle and heart. The downstream events explaining tissue-specific phenotype-genotype relations remained unclear. We investigated the mitochondrial function of GARS in human cell lines and in the Gars C210R mouse model. Human-induced neuronal progenitor cells (iNPCs) carrying dominant and recessive GARS mutations showed alterations of mitochondrial proteins, which were more prominent in iNPCs with dominant, neuropathy-causing mutations. Although comparative proteomic analysis of iNPCs showed significant changes in mitochondrial respiratory chain complex subunits, assembly genes, Krebs cycle enzymes and transport proteins in both recessive and dominant mutations, proteins involved in fatty acid oxidation were only altered by recessive mutations causing mitochondrial cardiomyopathy. In contrast, significant alterations of the vesicle-associated membrane protein-associated protein B (VAPB) and its downstream pathways such as mitochondrial calciumuptake and autophagy were detected in dominant GARS mutations. The role of VAPB has been supported by similar results in the Gars C210R mice. Our data suggest that altered mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) may be important disease mechanisms leading to neuropathy in this condition

Mutations in glycyl-tRNA synthetase impair mitochondrial metabolism in neurons.

The nuclear-encoded glycyl-tRNA synthetase gene (GARS) is essential for protein translation in both cytoplasm and mitochondria. In contrast, different genes encode the mitochondrial and cytosolic forms of most other tRNA synthetases. Dominant GARS mutations were described in inherited neuropathies, while recessive mutations cause severe childhood-onset disorders affecting skeletal muscle and heart. The downstream events explaining tissue-specific phenotype-genotype relations remained unclear. We investigated the mitochondrial function of GARS in human cell lines and in the GarsC210R mouse model. Human-induced neuronal progenitor cells (iNPCs) carrying dominant and recessive GARS mutations showed alterations of mitochondrial proteins, which were more prominent in iNPCs with dominant, neuropathy-causing mutations. Although comparative proteomic analysis of iNPCs showed significant changes in mitochondrial respiratory chain complex subunits, assembly genes, Krebs cycle enzymes and transport proteins in both recessive and dominant mutations, proteins involved in fatty acid oxidation were only altered by recessive mutations causing mitochondrial cardiomyopathy. In contrast, significant alterations of the vesicle-associated membrane protein-associated protein B (VAPB) and its downstream pathways such as mitochondrial calcium uptake and autophagy were detected in dominant GARS mutations. The role of VAPB has been supported by similar results in the GarsC210R mice. Our data suggest that altered mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) may be important disease mechanisms leading to neuropathy in this condition