Performance management in Thai R&D organizations : exploring the interplay between R&D institutions and R&D contexts

Measuring research and development (R&D) performance has become a fundamental concern for R&D organisations. However, the complexity of measurement problems in R&D organisations has resulted in a situation where there is an excess of literature around the areas of R&D measurement, and yet a scarcity of generally accepted measurement approaches (Brown & Gobeli, 1992). This might be because the design of performance measurement (PM) for an R&D organisation combines several interrelated contexts that make each R&D measurement unique. This thesis, therefore, reviews several major R&D distinctions which should be taken into account when the R&D PM design is considered. These considerations are R&D measurement levels and perspectives, R&D key measures, R&D key drivers, and types of R&D institutions.;Taking a quality-based approach, the thesis combines several techniques, i.e. in-depth interviews, cognitive mapping interviews, document analysis, multiple case studies, and cross-case analysis. The interviews involve 30 respondents who are all experienced in R&D management in four different Thai R&D institutes, under the Ministry of Science and Technology.;The results indicate issues in three areas of investigation. First, the four cases studied measure R&D performance at different levels, for different purposes, and applying different measures and techniques. At a corporate level, instead of emphasising financial areas, the output measurement seems to be significant, as well as deliberative to quantitative methods. Meanwhile, at a team level, the measures highlight both quantitative and qualitative measures, for the purpose of monitoring the process and progress of research.;Second, the output mixes, stage of R&D, and sources of research questions could lead to the identification of three major types of R&D organisations: discipline-based, profession-based, and domain-based. The R&D measures that a firm applies seem to be interrelated with the type of R&D institution that firm represents.;Finally, the main key driver in this study is R&D collaboration. However, collaboration functions differ according to the different types of R&D organisations. A discipline-based organisation tends to use collaboration as a tool to explore new knowledge and to strengthen the firm's competency, whereas a profession-based organisation tends to use collaboration to gain market information and increase its ability to utilise R&D.;The study developed implications of both theoretical and managerial importance, identifying patterns of interrelationship between R&D institutions and key performance measures, and between R&D institutions and their collaboration mechanisms. Additionally, the main managerial implication could benefit R&D management practitioners, R&D managers, and R&D policymakers. Overall, the study's results demonstrate the importance of understanding the constraints of each R&D measurement context, i.e. levels of measurement, areas of measurement, and stages of R&D, for the performance measurement system.;Also, this study shows that each type of R&D institute may significantly be interrelated with other features, i.e. with key measures, and with key driver's mechanisms. Conducive to measuring and managing R&D performance efficiently, managers may realise the unique role of each type of R&D organisation (as well as its key measures and performance drivers) and design their performance measurement accordingly. Therefore, the benefits of this study may be seen as practical knowledge which could be employed to design R&D PM and, ultimately, to complement a strategic formulation to improve a firm's R&D performance.Measuring research and development (R&D) performance has become a fundamental concern for R&D organisations. However, the complexity of measurement problems in R&D organisations has resulted in a situation where there is an excess of literature around the areas of R&D measurement, and yet a scarcity of generally accepted measurement approaches (Brown & Gobeli, 1992). This might be because the design of performance measurement (PM) for an R&D organisation combines several interrelated contexts that make each R&D measurement unique. This thesis, therefore, reviews several major R&D distinctions which should be taken into account when the R&D PM design is considered. These considerations are R&D measurement levels and perspectives, R&D key measures, R&D key drivers, and types of R&D institutions.;Taking a quality-based approach, the thesis combines several techniques, i.e. in-depth interviews, cognitive mapping interviews, document analysis, multiple case studies, and cross-case analysis. The interviews involve 30 respondents who are all experienced in R&D management in four different Thai R&D institutes, under the Ministry of Science and Technology.;The results indicate issues in three areas of investigation. First, the four cases studied measure R&D performance at different levels, for different purposes, and applying different measures and techniques. At a corporate level, instead of emphasising financial areas, the output measurement seems to be significant, as well as deliberative to quantitative methods. Meanwhile, at a team level, the measures highlight both quantitative and qualitative measures, for the purpose of monitoring the process and progress of research.;Second, the output mixes, stage of R&D, and sources of research questions could lead to the identification of three major types of R&D organisations: discipline-based, profession-based, and domain-based. The R&D measures that a firm applies seem to be interrelated with the type of R&D institution that firm represents.;Finally, the main key driver in this study is R&D collaboration. However, collaboration functions differ according to the different types of R&D organisations. A discipline-based organisation tends to use collaboration as a tool to explore new knowledge and to strengthen the firm's competency, whereas a profession-based organisation tends to use collaboration to gain market information and increase its ability to utilise R&D.;The study developed implications of both theoretical and managerial importance, identifying patterns of interrelationship between R&D institutions and key performance measures, and between R&D institutions and their collaboration mechanisms. Additionally, the main managerial implication could benefit R&D management practitioners, R&D managers, and R&D policymakers. Overall, the study's results demonstrate the importance of understanding the constraints of each R&D measurement context, i.e. levels of measurement, areas of measurement, and stages of R&D, for the performance measurement system.;Also, this study shows that each type of R&D institute may significantly be interrelated with other features, i.e. with key measures, and with key driver's mechanisms. Conducive to measuring and managing R&D performance efficiently, managers may realise the unique role of each type of R&D organisation (as well as its key measures and performance drivers) and design their performance measurement accordingly. Therefore, the benefits of this study may be seen as practical knowledge which could be employed to design R&D PM and, ultimately, to complement a strategic formulation to improve a firm's R&D performance

Fruit crops, 1982: a summary of research

Influence of six rootstocks and herbicides on growth, cropping, and fruit quality of Blaxtayman apple trees / David C. Ferree and Robert G. Hill, Jr. -- Tree performance and yield efficiency of several apple cultivars on M9 and M9 interstems / D. C. Ferree -- Chemical induction of lateral shoots on young apple trees / S. C. Myers and D. C. Ferree -- The influence of urea sprays, mulch, and pruning on apple tree decline / G. A. Cahoon and C. W. Donoho, Jr. -- Influence of fireblight and ambrosia beetle on several apple cultivars on M9 and M9 interstems / F. R. Hall, M. A. Ellis, and D. C. Ferree -- A model study of the effect of wind on air sprayer jets / R. D. Fox, D. L. Reichard, and R. D. Brazee -- A comparative study of selected vineyard training and pruning systems for 'Concord' grapevines / G. A. Cahoon -- Effects of selected soil applied herbicides on grapes / Jomo MacDermot and Garth A. Cahoon -- Evaluation of aromatic compounds and virgin females as attractants for rose chafer / Roger N. Williams, Terrence P. McGovern, and Michael Klein -- Botrytis cinerea "gray mold" isolates from strawberry resistant to benlate in Ohio / P. Tanboon-Ek and M. A. Elli

The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation

Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases to PI3K inhibitors, resulting in marked tumor growth delay and improvement in mouse survival. These data provide a mechanistic basis for therapeutic resistance in the brain microenvironment and identify translatable treatment strategies for HER2-amplified and/or PIK3CA-mutant breast cancer brain metastases

Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores

The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization

Biallelic variants in LIG3 cause a novel mitochondrial neurogastrointestinal encephalomyopathy

none67si: Abnormal gut motility is a feature of several mitochondrial encephalomyopathies, and mutations in genes such as TYMP and POLG, have been linked to these rare diseases. The human genome encodes three DNA ligases, of which only one, ligase III (LIG3), has a mitochondrial splice variant and is crucial for mitochondrial health. We investigated the effect of reduced LIG3 activity and resulting mitochondrial dysfunction in seven patients from three independent families, who showed the common occurrence of gut dysmotility and neurological manifestations reminiscent of mitochondrial neurogastrointestinal encephalomyopathy. DNA from these patients was subjected to whole exome sequencing. In all patients, compound heterozygous variants in a new disease gene, LIG3, were identified. All variants were predicted to have a damaging effect on the protein. The LIG3 gene encodes the only mitochondrial DNA (mtDNA) ligase and therefore plays a pivotal role in mtDNA repair and replication. In vitro assays in patient-derived cells showed a decrease in LIG3 protein levels and ligase activity. We demonstrated that the LIG3 gene defects affect mtDNA maintenance, leading to mtDNA depletion without the accumulation of multiple deletions as observed in other mitochondrial disorders. This mitochondrial dysfunction is likely to cause the phenotypes observed in these patients. The most prominent and consistent clinical signs were severe gut dysmotility and neurological abnormalities, including leukoencephalopathy, epilepsy, migraine, stroke-like episodes, and neurogenic bladder. A decrease in the number of myenteric neurons, and increased fibrosis and elastin levels were the most prominent changes in the gut. Cytochrome c oxidase (COX) deficient fibres in skeletal muscle were also observed. Disruption of lig3 in zebrafish reproduced the brain alterations and impaired gut transit in vivo. In conclusion, we identified variants in the LIG3 gene that result in a mitochondrial disease characterized by predominant gut dysmotility, encephalopathy, and neuromuscular abnormalities.This work was supported by Telethon Grant GGP15171 to E.B. and R.D.G. and by a donation from Kobe city to the Department of General Pediatrics, Kobe University Graduate School of Medicine (K550003302). S.C. was supported by a Dutch Cancer Foundation grant (KWF11011). V.C. and A.M. were supported by the Italian Ministry of Health (“Ricerca Corrente” funding). R.D.G. is the recipient of grants from University of Ferrara (FAR and FIR funds).openBonora, Elena; Chakrabarty, Sanjiban; Kellaris, Georgios; Tsutsumi, Makiko; Bianco, Francesca; Bergamini, Christian; Ullah, Farid; Isidori, Federica; Liparulo, Irene; Diquigiovanni, Chiara; Masin, Luca; Rizzardi, Nicola; Cratere, Mariapia Giuditta; Boschetti, Elisa; Papa, Valentina; Maresca, Alessandra; Cenacchi, Giovanna; Casadio, Rita; Martelli, Pierluigi; Matera, Ivana; Ceccherini, Isabella; Fato, Romana; Raiola, Giuseppe; Arrigo, Serena; Signa, Sara; Sementa, Angela Rita; Severino, Mariasavina; Striano, Pasquale; Fiorillo, Chiara; Goto, Tsuyoshi; Uchino, Shumpei; Oyazato, Yoshinobu; Nakamura, Hisayoshi; Mishra, Sushil K; Yeh, Yu-Sheng; Kato, Takema; Nozu, Kandai; Tanboon, Jantima; Morioka, Ichiro; Nishino, Ichizo; Toda, Tatsushi; Goto, Yu-Ichi; Ohtake, Akira; Kosaki, Kenjiro; Yamaguchi, Yoshiki; Nonaka, Ikuya; Iijima, Kazumoto; Mimaki, Masakazu; Kurahashi, Hiroki; Raams, Anja; MacInnes, Alyson; Alders, Mariel; Engelen, Marc; Linthorst, Gabor; de Koning, Tom; den Dunnen, Wilfred; Dijkstra, Gerard; van Spaendonck, Karin; van Gent, Dik C; Aronica, Eleonora M; Picco, Paolo; Carelli, Valerio; Seri, Marco; Katsanis, Nicholas; Duijkers, Floor A M; Taniguchi-Ikeda, Mariko; De Giorgio, RobertoBonora, Elena; Chakrabarty, Sanjiban; Kellaris, Georgios; Tsutsumi, Makiko; Bianco, Francesca; Bergamini, Christian; Ullah, Farid; Isidori, Federica; Liparulo, Irene; Diquigiovanni, Chiara; Masin, Luca; Rizzardi, Nicola; Cratere, Mariapia Giuditta; Boschetti, Elisa; Papa, Valentina; Maresca, Alessandra; Cenacchi, Giovanna; Casadio, Rita; Martelli, Pierluigi; Matera, Ivana; Ceccherini, Isabella; Fato, Romana; Raiola, Giuseppe; Arrigo, Serena; Signa, Sara; Sementa, Angela Rita; Severino, Mariasavina; Striano, Pasquale; Fiorillo, Chiara; Goto, Tsuyoshi; Uchino, Shumpei; Oyazato, Yoshinobu; Nakamura, Hisayoshi; Mishra, Sushil K; Yeh, Yu-Sheng; Kato, Takema; Nozu, Kandai; Tanboon, Jantima; Morioka, Ichiro; Nishino, Ichizo; Toda, Tatsushi; Goto, Yu-Ichi; Ohtake, Akira; Kosaki, Kenjiro; Yamaguchi, Yoshiki; Nonaka, Ikuya; Iijima, Kazumoto; Mimaki, Masakazu; Kurahashi, Hiroki; Raams, Anja; MacInnes, Alyson; Alders, Mariel; Engelen, Marc; Linthorst, Gabor; de Koning, Tom; den Dunnen, Wilfred; Dijkstra, Gerard; van Spaendonck, Karin; van Gent, Dik C; Aronica, Eleonora M; Picco, Paolo; Carelli, Valerio; Seri, Marco; Katsanis, Nicholas; Duijkers, Floor A M; Taniguchi-Ikeda, Mariko; De Giorgio, Robert

Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores.

The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization

Physiological and Expression Analyses of Agrobacterium tumefaciens trxA, Encoding Thioredoxin▿

Exposure of Agrobacterium tumefaciens to menadione, cumene hydroperoxide, and diamide strongly induced trxA expression. The trxA mutant showed a reduction in the aerobic growth rate and plating efficiency and was cytochrome c oxidase negative. Atypically, the mutant has decreased resistance to menadione but an increased H2O2 resistance phenotype