Naar een verklaring van R&D organisatievormen

Inleiding. Het onderzoek naar de diverse vormen van samenwerking tussen organisaties, bijvoorbeeld joint ventures en strategische allianties, speelt zich doorgaans af op het analyseniveau van de organisaties zelf. Aan samenwerkingsverbanden tussen organisaties op een functioneel managementgebied, bijvoorbeeld produktie, Research & Development (R&D) en marketing, wordt in de literatuur minder aandacht besteed. Terwijl produktie en met name R&D voor veel ondernemingen in de jaren negentig tot de belangrijkste functionele managementgebieden zullen gaan behoren (Porter, 1990). Levenscycli van diverse produkten zullen verkorten door versnelde technologische ontwikkeling, zich snel wijzigende consumentenvoorkeuren en hogere kwaliteitseisen. Hierdoor zullen veel ondernemingen gedwongen zijn tot het opvoeren van hun R&D inspanning, zelf of in samenwerking met anderen, en flexibilisering van de organisatiestructuur...

Make, buy or cooperate decisions with respect to research and development in international business networks

Introduction. Research and Development (R&D) is one of the most important business activities of the next decade (Porter, 1990). Commercialization of technological know how is essential for survival of firms (Teece, 1987). Organizational forms of R&D are one of the main competitive advantages of firms. The importance of cooperative agreements and networks as an alternative for in-house R&D is increasing (E.C., 1991; OTA, 1990). Collaborative agreements are of strategic importance for a firm (Hakansson, 1990). The number of international cooperative agreements has increased. For example, more than 30% of cooperative agreements in biotechnology are between companies from different parts of the world (Hagedoorn & Schakenraad, 1990)...

Functional analysis of novel androgen receptor mutations in a unique cohort of Indonesian patients with a disorder of sex development

Mutations in the androgen receptor (AR) gene, rendering the AR protein partially or completely inactive, cause androgen insensitivity syndrome, which is a form of a 46,XY disorder of sex development (DSD). We present 3 novel AR variants found in a cohort of Indonesian DSD patients: p.I603N, p.P671S, and p.Q738R. The aim of this study was to determine the possible pathogenic nature of these newly found unclassified variants. To investigate the effect of these variants on AR function, we studied their impact on transcription activation, AR ligand-binding domain interaction with an FxxLF motif containing peptide, AR subcellular localization, and AR nuclear dynamics and DNA-binding. AR-I603N had completely lost its transcriptional activity due to disturbed DNA-binding capacity and did not show the 114-kDa hyperphosphorylated AR protein band normally detectable after hormone binding. The patient with AR-I603N displays a partial androgen insensitivity syndrome phenotype, which is explained by somatic mosaicism. A strongly reduced transcriptional activity was observed for AR-Q738R, together with diminished interaction with an FxxLF motif containing peptide. AR-P671S also showed reduced transactivation ability, but no change in DNA- or FxxLF-binding capacity and interferes with transcriptional activity for as yet unclear reasons

Organisatievormen van Research en Development als Managementvraagstuk

keywords: worden binnen ondememingen organisatievormen wordt tussen hebben ondememing aantal verklarende model project hoofdstuk paragraaf technologische kunnen welke management kenni ontwikkelingstermij

Variable loss of functional activities of androgen receptor mutants in patients with androgen insensitivity syndrome

Androgen receptor (AR) mutations in androgen insensitivity syndrome (AIS) are associated with a variety of clinical phenotypes. The aim of the present study was to compare the molecular properties and potential pathogenic nature of 8 novel and 3 recurrent AR variants with a broad variety of functional assays. Eleven AR variants (p.Cys177Gly, p.Arg609Met, p.Asp691del, p.Leu701Phe, p.Leu723Phe, p.Ser741Tyr, p.Ala766Ser, p.Arg775Leu, p.Phe814Cys, p.Lys913X, p.Ile915Thr) were analyzed for hormone binding, transcriptional activation, cofactor binding, translocation to the nucleus, nuclear dynamics, and structural conformation. Ligand-binding domain variants with low to intermediate transcriptional activation displayed aberrant Kd values for hormone binding and decreased nuclear translocation. Transcriptional activation data, FxxFF-like peptide binding and DNA binding correlated well for all variants, except for p.Arg609Met, p.Leu723Phe and p.Arg775Leu, which displayed a relatively higher peptide binding activity. Variants p.Cys177Gly, p.Asp691del, p.Ala766Ser, p.Phe814Cys, and p.Ile915Thr had intermediate or wild type values in all assays and showed a predominantly nuclear localization in living cells. All transcriptionally inactive variants (p.Arg609Met, p.Leu701Phe, p.Ser741Tyr, p.Arg775Leu, p.Lys913X) were unable to bind to DNA and were associated with complete AIS. Three variants (p.Asp691del, p.Arg775Leu, p.Ile915Thr) still displayed significant functional activities in in vitro assays, although the clinical phenotype was associated with complete AIS. The data show that molecular phenotyping based on 5 different functional assays matched in most (70%) but not all cases. Copyrigh

Organisatievormen van research en development als managementvraagstuk

keywords: worden binnen ondememingen organisatievormen wordt tussen hebben ondememing aantal verklarende model project hoofdstuk paragraaf technologische kunnen welke management kenni ontwikkelingstermij

Complete APTX deletion in a patient with ataxia with oculomotor apraxia type 1

Background: Ataxia with oculomotor apraxia type 1 is an autosomal-recessive neurodegenerative disorder characterized by a childhood onset of slowly progressive cerebellar ataxia, followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy. Ataxia with oculomotor apraxia type 1 is caused by bi-allelic mutations in APTX (chromosome 9p21.1). Case presentation: Our patient has a clinical presentation that is typical for ataxia with oculomotor apraxia type 1 with no particularly severe phenotype. Multiplex Ligation-dependent Probe Amplification analysis resulted in the identification of a homozygous deletion of all coding APTX exons (3 to 9). SNP array analysis using the Illumina Infinium CytoSNP-850 K microarray indicated that the deletion was about 62 kb. Based on the SNP array results, the breakpoints were found using direct sequence analysis: c.-5 + 1225_*44991del67512, p.0?. Both parents were heterozygous for the deletion. Homozygous complete APTX deletions have been described in literature for two other patients. We obtained a sample from one of these two patients and characterized the deletion (156 kb) as c.-23729_*115366del155489, p.0?, including the non-coding exons 1A and 2 of APTX. The more severe phenotype reported for this patient is not observed in our patient. It remains unclear whether the larger size of the deletion (156 kb vs 62 kb) plays a role in the phenotype (no extra genes are deleted). Conclusion: Here we described an ataxia with oculomotor apraxia type 1 patient who has a homozygous deletion of the complete coding region of APTX. In contrast to the patient with the large deletion, our patient does not have a severe phenotype. More patients with deletions of APTX are required to investigate a genotype-phenotype effect

Optimising water quality monitoring to understand biogeochemical processes in UK rivers and reservoirs

This thesis explores how high-frequency sensor data can improve understanding of environmental and biogeochemical conditions in inland water bodies, particularly for predicting cyanobacteria-related taste and odour (T&O) compounds geosmin and 2-MIB in drinking water reservoirs. Since these compounds cannot be directly measured in situ, alternative predictors are required. High-frequency hydrochemical sensor data from six UK rivers showed that a minimum measurement frequency of four hours was required to capture the necessary variation in the parameters. For T&O prediction, key drivers need to be identified that high-frequency sensors can measure. These drivers were studied in laboratory microcosms with reservoir water, which found that nutrient ratios (N:P and NH4+:NO3-) and concentrations impacted phytoplankton productivity, community composition and the production of 2-MIB. 2-MIB production was linked to benthic cyanobacteria (Leptolyngbya spp. and Pseudanabaena spp.) and community productivity, with total nitrogen being a stronger predictor than nutrient ratios, but P-limitation also played a role. NH4+ caused rapid ‘boom-bust’ growth, while NO3- led to more balanced growth four days later. Long-term manual sampling and sensor data from 2022-2023 in the same reservoir showed that optimal weather conditions led to increased productivity and a delayed T&O response. Geosmin concentrations (likely from planktic cyanobacteria) increased 1-2 weeks after high solar energy and low rainfall, while 2-MIB (likely from benthic cyanobacteria) was linked to high temperatures and low wind gusts 2-3 weeks earlier. While N:P and NH4+:NO3- ratios were direct predictors of geosmin and 2-MIB, these are not useful for an early-warning system, because elevated NH4+ and PO43- concentrations were likely related to internal loading and T&O release after cell death. The most useful predictors were environmental parameters that support phytoplankton growth (seasonality, solar energy, air temperature, precipitation and wind speed), indirect growth indicators (dissolved oxygen, vertical mixing), and measurements of inflows to the reservoir via a tributary (NO3--N, PO43--P, NH4+-N or EC and turbidity, alongside discharge). Appropriate in situ measurement of these factors, especially when combined with weather forecasts, can provide early warnings of T&O events that can guide water treatment management

Berry Twist: a Twisting-Tube Soft Robotic Gripper for Blackberry Harvesting

As global demand for fruits and vegetables continues to rise, the agricultural industry faces challenges in securing adequate labor. Robotic harvesting devices offer a promising solution to solve this issue. However, harvesting delicate fruits, notably blackberries, poses unique challenges due to their fragility. This study introduces and evaluates a prototype robotic gripper specifically designed for blackberry harvesting. The gripper features an innovative fabric tube mechanism employing motorized twisting action to gently envelop the fruit, ensuring uniform pressure application and minimizing damage. Three types of tubes were developed, varying in elasticity and compressibility using foam padding, spandex, and food-safe cotton cheesecloth. Performance testing focused on assessing each gripper's ability to detach and release blackberries, with emphasis on quantifying damage rates. Results indicate the proposed gripper achieved an 82% success rate in detaching blackberries and a 95% success rate in releasing them, showcasing the promised potential for robotic harvesting applications

Benefit of wearing an activity tracker in sarcoidosis

Sarcoidosis causes many disabling symptoms, including fatigue and exercise limitations, which have been shown to improve by physical activity programs. The aim of this study was to estimate the effect of continuous activity monitoring using an electronic activity tracker (AT) on exercise performance and fatigue of sarcoidosis patients, compared to controls (cohort study), and the effect of additional personal coaching (randomized trial) over a period of 3 months. Fifty-four sarcoidosis patients received an AT (Group Ia: 27 with coaching and Group Ib: 27 without). A historical group of sarcoidosis patients (Group II;n= 41) who did not follow a physical activity program served as controls. Exercise performance of patients wearing an AT (Group I) improved compared with controls (Group II), including the 6MWD, % predicted ( increment 4.4 +/- 9.1 versus increment 0.7 +/- 5.0, respectively), and fatigue levels decreased ( increment -3.9 +/- 5.7 versus increment -1.8 +/- 5.3). Patients with coaching (Group Ia) showed greater improvement of exercise capacity over time than patients without coaching (Group Ib) as shown by the Steep Ramp Test results (watts: increment 20.2 +/- 33.8 versus increment 5.7 +/- 26.4; and SRT, VO(2)max, % predicted: increment 1.6 +/- 2.6 versus increment 0.7 +/- 2.3). Sarcoidosis patients wearing an AT achieved improvement of exercise performance and reduction of fatigue. We therefore recommend encouraging sarcoidosis patients to wear an AT to stimulate physical activity and reduce fatigue. The additional benefit of coaching needs to be explored in future studies