The organisational decomposition of the innovation process : what does it mean for the global distribution of innovation activities?

The starting point for this paper is a fundamental change currently occurring in the way innovation is organised in the developed countries: it tended to be centralised at or near headquarters but is now much more decentralised within the company. Equally if not more significant, innovation activities that used to be carried out inhouse by innovating firms themselves are carried out by independent suppliers of knowledge intensive business services, or are transferred to key suppliers. The question driving this paper is how this ‘organisational decomposition of the innovation process’ changes the global distribution of innovation of activities. Does it contribute to their global dispersal to the developing world or does it strengthen the existing concentration? Since this is uncharted territory the paper seeks guidance from theory and lays out an agenda for empirical research. Keywords: innovation; outsourcing; global; knowledge; innovation system; global value chain

Has NANOGrav found first evidence for cosmic strings?

The North American Nanohertz Observatory for Gravitational Waves (NANOGrav) has recently reported strong evidence for a stochastic common-spectrum process affecting the pulsar timing residuals in its 12.5-year data set. We demonstrate that this process admits an interpretation in terms of a stochastic gravitational-wave background emitted by a cosmic-string network in the early Universe. We study stable Nambu-Goto strings in dependence of their tension $G\mu$ and loop size $\alpha$ and show that the entire viable parameter space will be probed by an array of future experiments.Comment: 7 pages, 3 figures. v2: revised treatment of the higher cosmic-string modes [see Eq. (6)], resulting in a few numerical but no qualitative changes. v3: matches version published in PR

A Data Quality Metrics Hierarchy for Reliability Data

In this paper, we describe an approach to understanding data quality issues in field data used for the calculation of reliability metrics such as availability, reliability over time, or MTBF. The focus lies on data from sources such as maintenance management systems or warranty databases which contain information on failure times, failure modes for all units. We propose a hierarchy of data quality metrics which identify and assess key problems in the input data. The metrics are organized in such a way that they guide the data analyst to those problems with the most impact on the calculation and provide a prioritised action plan for the improvement of data quality. The metrics cover issues such as missing, wrong, implausible and inaccurate data. We use examples with real-world data to showcase our software prototype and to illustrate how the metrics have helped with data preparation. Using this way, analysts can reduce the amount of wrong conclusions drawn from the data to mistakes in the input values

Genome scale model reconstruction of the methylotrophic yeast Ogataea polymorpha

Ogataea polymorpha is a thermotolerant, methylotrophic yeast with significant industrial applications. It is a promising host to generate platform chemicals from methanol, derived e.g. from carbon capture and utilization streams. Full development of the organism into a production strain requires additional strain design, supported by metabolic modeling on the basis of a genome-scale metabolic model. However, to date, no genome-scale metabolic model is available for O. polymorpha. To overcome this limitation, we used a published reconstruction of the closely related yeast Pichia pastoris as reference and corrected reactions based on KEGG annotations. Additionally, we conducted phenotype microarray experiments to test O. polymorpha’s metabolic capabilities to grown on or respire 192 different carbon sources. Over three-quarter of the substrate usage was correctly reproduced by the model. However, O. polymorpha failed to metabolize eight substrates and gained 38 new substrates compared to the P. pastoris reference model. To enable the usage of these compounds, metabolic pathways were inferred from literature and database searches and potential enzymes and genes assigned by conducting BLAST searches. To facilitate strain engineering and identify beneficial mutants, gene-protein-reaction relationships need to be included in the model. Again, we used the P. pastoris model as reference to extend the O. polymorpha model with this relevant information. The final metabolic model of O. polymorpha supports the engineering of synthetic metabolic capabilities and enabling the optimization of production processes, thereby supporting a sustainable future methanol econom

Modular cytosine base editing promotes epigenomic and genomic modifications

Prokaryotic and eukaryotic adaptive immunity differ considerably. Yet, their fundamental mechanisms of gene editing via Cas9 and activation-induced deaminase (AID), respectively, can be conveniently complimentary. Cas9 is an RNA targeted dual nuclease expressed in several bacterial species. AID is a cytosine deaminase expressed in germinal centre B cells to mediate genomic antibody diversification. AID can also mediate epigenomic reprogramming via active DNA demethylation. It is known that sequence motifs, nucleic acid structures, and associated co-factors affect AID activity. But despite repeated attempts, deciphering AID’s intrinsic catalytic activities and harnessing its targeted recruitment to DNA is still intractable. Even recent cytosine base editors are unable to fully recapitulate AID’s genomic and epigenomic editing properties. Here, we describe the first instance of a modular AID-based editor that recapitulates the full spectrum of genomic and epigenomic editing activity. Our ‘Swiss army knife’ toolbox will help better understand AID biology per se as well as improve targeted genomic and epigenomic editing

O FENÔMENO EVASÃO NOS CURSOS SUPERIORES DE TECNOLOGIA: UM ESTUDO DE CASO EM UMA UNIVERSIDADE PÚBLICA NO SUL DO BRASIL

A pesquisa teceu o perfil do evadido dos cursos superiores de tecnologia, em uma instituição de ensino superior no sul do Brasil. Relacionou-se os motivos da desistência do curso, assim como elucidou alternativas de permanência na universidade para conter a evasão. Fez-se revisão bibliográfica em artigos publicados em periódicos Qualis, e após entrevista com evadidos deu via contato telefônico, e-mail e questionário por meio do software Lime Survey. Os resultados revelam que homens evadem mais que mulheres. A evasão ocorre no intervalo de idade entre 20 e 29 anos. O motivo mais frequente é a troca de curso na IES seguido de ingresso em outra IES. A sensação de abandono infere sentimentos de perda, de fracasso. Tais sensações remetem a um compromisso maior nos projetos pedagógicos em curso, à reações que otimizem o diálogo e talvez a permanência desse aluno na universidade, à criação de uma rede de relacionamentos dos ingressos e egressos. Ações psicopedagógicas prospectivas e maior flexibilidade curricular podem conter a evasão, assim como uma política institucional que considere um número significativo de bolsas de permanência. A educação isolada não muda as pessoas, mas sem educação não há rupturas. O sentimento de pertencimento parece ser o desafio para conter-se a evasão no ensino superior brasileiro

Heparin-guided binding of vascular endothelial growth factor to supramolecular biomaterial surfaces

Growth factors can steer the biological response to a biomaterial post implantation. Heparin is a growth factor binding molecule that can coordinate growth factor presentation to cells and therefore is able to regulate many biological processes. One way to functionalize biomaterials with heparin and growth factors is via a supramolecular approach. Here, we show a proof-of-concept study in which a supramolecular approach based on ureido-pyrimidinone (UPy) was used, which allows for modular functionalization. PCLdiUPy was functionalized with a UPy-modified heparin binding peptide (UPy-HBP) to facilitates binding of heparin, which in turn can bind vascular endothelial growth factor (VEGF) via its heparin binding domain. The adsorption of both heparin and VEGF were studied in two different functionalization approaches (pre-complex and two-step) and at different molecular ratios. Quartz crystal microbalance with dissipation energy adsorption data showed that VEGF and pre-complexed heparin:VEGF adsorbed non-specifically, with no distinguish between non-specific adsorption and heparin guided-adsorption. On the biological side, heparin guided-adsorption of Heparin:VEGF enhanced HUVECs surface coverage as compared to non-specific adsorption. These results provide a detailed insight on the molecular sandwich which is useful for new design strategies of supramolecular biomaterials with well-controlled immobilization of different growth factors.</p

A systematic review of home-based dietary interventions during radiation therapy for cancer.

Purpose: Our objectives are to assess (1) the acceptability and feasibility of dietary interventions for patients undergoing radiation therapy (RT), and (2) the impact of dietary interventions on patient reported outcomes, toxicities, and survival. Methods: A PICOS/PRISMA/MOOSE selection protocol was used to include articles that evaluate adding dietary interventions to patients receiving RT. Acceptability was defined as (# accepting/# approached); feasibility was (# completing/# approached). Patient-reported outcomes were reported based on questionnaires used in each study and survival was measured from the date of diagnosis until death in each study. Level of evidence was assessed with Center for Evidence-Based Medicine (CEBM) criteria. Results: Sixteen articles were included; among these, 2027 patients were approached regarding the intervention, and 1661 accepted (81.9%); of these, 1543 (92.9%) completed the prescribed diet + RT course. The most common cancers included were gynecological, head and neck, and gastrointestinal. For patients with pelvic cancers, a high fiber diet may improve diarrhea (CEBM level 1b). Enteral nutrition formula, including formulas with proteins such as L-arginine, lipids such as eicosapentaenoic acids, glucids, and ribonucleotides, may help prevent of malnutrition in head and neck cancer patients undergoing RT (level 2b). Vitamin C and β-carotene may reduce of xerostomia in head and neck cancer patients; however, the studies evaluating these vitamins included vitamin E, which increases all-cause mortality (level 2b). No dietary intervention for cancer patients receiving RT has been shown to improve survival. Conclusion: There are limited data to support safe and efficacious use of dietary interventions during RT

Depression mediates the association between health literacy and health-related quality of life after myocardial infarction

IntroductionSo far, health literacy (HL) and its related factors in patients with acute myocardial infarction received little attention. Thus, the objective of this study was to investigate the associations between the different dimensions of HL and disease-specific health-related quality of life (HRQOL), and factors that may affect these relations in patients after acute myocardial infarction (AMI).MethodsAll survivors of AMI between June 2020 and September 2021, from the Myocardial Infarction Registry Augsburg (n=882) received a postal questionnaire on HL [Health Literacy Questionnaire (HLQ)], HRQOL (MacNew Heart Disease HRQOL questionnaire) and depression (Patient Health Questionnaire). From the 592 respondents, 546 could be included in the analysis. Multivariable linear regression models were performed to investigate the associations between the nine subscales of the HLQ and the total score and three subscales of the MacNew questionnaire. A mediation analysis was performed to estimate direct and indirect effects of HL on HRQOL taking into account the mediating effect of depression.ResultsIn the sample of 546 patients (72.5% male, mean age 68.5 ± 12.2 years), patients with poor education showed significantly lower HLQ scores. Significant associations between the subscales of the HLQ and the MacNew were found, which remained significant after adjustment for sociodemographic variables with few exceptions. More than 50% of the association between HL and HRQOL was mediated by depression in seven HLQ subscales and a complete mediating effect was found for the HLQ subscales ‘Actively managing my health’ and ‘Appraisal of health information’.DiscussionDepression mediates the associations between HL and disease-specific HRQOL in patients with myocardial infarction

Mode of action-based risk assessment of genotoxic carcinogens

The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group. In contrast, genotoxic carcinogens, their metabolic precursors and DNA reactive metabolites are considered to represent risk factors at all concentrations since even one or a few DNA lesions may in principle result in mutations and, thus, increase tumour risk. Within the current document, an updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as “omics” approaches. Furthermore, wherever possible and appropriate, special attention is given to the integration of background levels of the same or comparable DNA lesions. Within part A, fundamental considerations highlight the terms hazard and risk with respect to DNA reactivity of genotoxic agents, as compared to non-genotoxic agents. Also, current methodologies used in genetic toxicology as well as in dosimetry of exposure are described. Special focus is given on the elucidation of modes of action (MOA) and on the relation between DNA damage and cancer risk. Part B addresses specific examples of genotoxic carcinogens, including those humans are exposed to exogenously and endogenously, such as formaldehyde, acetaldehyde and the corresponding alcohols as well as some alkylating agents, ethylene oxide, and acrylamide, but also examples resulting from exogenous sources like aflatoxin B$_{1}$, allylalkoxybenzenes, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), benzo[a]pyrene and pyrrolizidine alkaloids. Additionally, special attention is given to some carcinogenic metal compounds, which are considered indirect genotoxins, by accelerating mutagenicity via interactions with the cellular response to DNA damage even at low exposure conditions. Part C finally encompasses conclusions and perspectives, suggesting a refined strategy for the assessment of the carcinogenic risk associated with an exposure to genotoxic compounds and addressing research needs