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Functionalized S,N-heteropentacenes SN5’ were used as central donor unit in molecular donor-acceptor dyads and covalently linked to fullerenic acceptor units via flexible linker. Systematically varied structural motifs and characterization of...

A novel and versatile method for the N‐arylation of dithieno[3,2‐b:2′,3′‐d]pyrrole (DTP) is presented. By Pd‐ or Cu‐catalyzed coupling a variety of arenes and acenes were directly attached at the DTP−nitrogen yielding a variety of functionalized DTPs. Investigations on optical and redox properties led to valuable structure‐property relationships, which were corroborated by quantum chemical calculations. Further functionalization and elongation of the conjugation of an acceptor‐substituted DTP was elaborated to result in complex cruciform‐type donor−acceptor oligomers, which were investigated and implemented in single material organic solar cells., A versatile method is presented for the direct N‐arylation of dithieno[3,2‐b:2′,3′‐d]pyrrole (DTP) providing a variety of functionalized derivatives. Three catalyst systems were explored, whereby Pd2dba3/tBu3P showed broad applicability with good yields throughout. Investigations on optical and redox properties led to valuable structure‐property relationships. Further functionalization of an acceptor‐substituted DTP yielded cruciform‐type donor−acceptor oligomers, which were implemented into single material organic solar cells.

Ambifunctional heterpentacenes with the heteroatom sequence SSNSS in the ladder‐type backbone were used either as donor or as nonfullerenic acceptor in solution‐processed bulk‐heterojunction solar cells. Different acceptor moieties and side chains were inserted. Synthesis and characterization of the systematically varied structural motifs provided insight in structure‐property relationships. Moreover, a dimeric heteroacene was synthesized, and the optoelectronic properties were compared to those of its monomeric counterpart., Functionalized S,N‐heteropentacenes SN5’ comprising annulated thiophene and pyrrole rings with the heteroatom sequence SSNSS in the ladder‐type backbone were developed with systematically varied structural motifs. Tunable frontier orbital energies allowed their application either as donor or as nonfullerenic acceptor in solution‐processed bulk‐heterojunction solar cells.

Digitalisation in agriculture is considered the fourth revolution in farming, which is expressed by a broad range of available digital technologies and data applications. Politicians and experts assume that smart farming technologies (SFT) have a strong potential to enhance economic performance of farming and will contribute to agricultural sustainability as they may increase precision of inputs to crops and soils based on site-specific needs, and link these aspects to farm management systems. This paper explores farmers' and other stakeholders’ perceptions and attitudes towards SFT in Germany with a multi-actor approach. Quantitative and qualitative data show that while there are generally positive attitudes, farmers are less enthusiastic with regard to expected positive effects of SFT for the environment. Also, there is still a number of adoption barriers on the technology level as well as due to an unfavorable institutional and infrastructural environment. Although a multi-actor approach was practiced, close cooperation of practitioners with developers were not frequently observed nor could they be easily supported through action-research. Notwithstanding, through the multi-actor approach, a comprehensive situational picture of SFT appraisal was composed and, a general raise of awareness among the respective AKIS actors generated.

Technological innovations are changing mechanisation in agriculture. The most recent wave of innovations referred to as smart farming technologies (SFT), promise to improve farming by responding to economic, ecological, and social challenges and thereby sustainably develop agriculture throughout Europe. To better understand the relevance of ongoing technological progress for farming systems across Europe, 287 farmers were surveyed in 7 EU countries and in 4 cropping systems, alongside 22 in-depth semi-structured interviews with experts from the agricultural knowledge and innovation system. Of the surveyed farmers, about 50% were SFT adopters and 50% were non-adopters. The number of adopters increased with farm size, and there were more adopters among arable cropping systems than in tree crops. Although all farmers broadly perceive SFT as useful to farming and generally expect SFT to continue to be so, when it comes to specific on-farm challenges, farmers are less convinced of SFT potential. Moreover, farmers’ perceptions of SFT vary according to SFT characteristics and farming context. Interestingly, both adopter and non-adopter groups are hesitant regarding SFT adoption, such that adopters are somewhat disillusioned about the SFT that they have experience with, and non-adopters because they are not convinced that the appropriate technologies are available and accessible. About 60% of all farmers surveyed have a number of suggestions for SFT to become more relevant to a broader range of farms. Both farmers and experts generally consider peer-to-peer communication as important sources of information and deplore a lack of impartial advice. Experts are generally more convinced of SFT advantages, and are positive regarding the long-term trends of technological development. The findings support previous findings on using farmers’ perceptions in innovation processes, and provide insight to the recent trends regarding SFT application to diverse cropping systems across Europe. This suggests that differences related to agricultural structures and farming systems across Europe have to be considered if SFT development and dissemination should be improved.

Resumo Enquadramento: As diferenças paradoxais identificadas entre a forma como as pessoas experienciam a dor, independente da sua intensidade, e o sofrimento a ela associado, relacionam-se com os sistemas de crenças e valores. Objetivos: Validar o Meaning in Suffering Test (MIST) para a população portuguesa e determinar as suas características psicométricas. Metodologia: Este estudo apresenta o processo de adaptação transcultural, realizado numa amostra de 187 pessoas com doença reumática músculo-esquelética (DRM), com recurso a questionário sociodemográfico, clínico e o MIST-P. Resultados: A amostra, maioritariamente do sexo feminino, tinha 49,9±12,1 anos. O MIST-P apresenta bons valores de fidelidade (alfa de Cronbach de 0,833). A análise fatorial determinou a organização dos 12 itens em 2 fatores: Sentido e respostas face ao sofrimento e Características subjetivas face ao sofrimento. A escala é estável no tempo (r = 0,844). Conclusão: O MIST-P é válido e fiável para a população portuguesa com DRM, tendo potencial para ser aplicado na investigação e na prática clínica de prevenção, controlo e integração do sofrimento inevitável.

Objective To assess the academic and professional background of school personnel; to assess the impact of the Diabetes + Support given by School Personnel to Children with Type 1 Diabetes Program on the school personnel’s knowledge and confidence to support students with type 1 diabetes; to compare their level of knowledge with the academic and professional variables of the school personnel. Methods A quasi-experimental pre-test/post-test study design without a Control Group. Study with a sample of 129 (before intervention – T0) and 113 (after intervention – T1) pre-school to secondary school personnel from participating schools, with at least one student with type 1 diabetes. The project was approved by the Ethics Committee of the Portuguese Ministry of Education. Results Most school personnel included in the study were teachers (51.2%). After training, they were more confident than before to support children with type 1 diabetes (p

New folic acid (FA) coupled three layered micelles (3LM) were designed to encapsulate DNA, and their application as delivery system that specifically targets activated macrophages was investigated for new treatment options in rheumatoid arthritis (RA). FA coupled poly(l-lactide)-b-poly(ethylene glycol) (FA-PEG-PLLA) was synthesized via the NHS-ester activated/amine coupling method. Fluorescein labeled folic acid was used for flow cytometric detection of the expression of functional folic receptor β in LPS-activated and resting macrophages. FA coupled 3LM were formulated in a two-step procedure and characterized regarding hydrodynamic diameters and zeta potentials. The presence of the targeting ligand was shown not to increase the size of the 3LM compared to their non-targeted counterparts. Targeted and non-targeted 3LM were used in vitro to optimize uptake conditions in the RAW 264.7 macrophage cell line. The amount of FA coupled polymer in the final formulation was found to be optimal at 75% FA-PEG-PLLA and 25% PLLA-PEG-PLLA. Subsequently, transgene expression in vitro in RAW 264.7 cells and ex vivo in primary activated and resting mouse macrophages was determined as a function of FR-mediated internalization of 3LM encapsulating GFP expressing plasmid. FR-overexpressing activated cells, as successfully identified by internalization of FA-fluorescein, showed significantly higher GFP expression in vitro and ex vivo than resting macrophages with only a basal level of FR expression. Lastly, injectable hydrogels as depot formulation were formed by stereocomplexation, and their degradation, DNA release profiles, and dissociation into intact 3LM were found to be beneficial for potential in vivo application. Our findings confirm that FA-3LM are taken up by activated macrophages via folate receptor mediated endocytosis and that their hydrogels release intact 3LM for efficient transfection of primary macrophages. Therefore, FA-3LM could become a promising delivery system for receptor-mediated drug or gene delivery and novel therapy for rheumatoid arthritis in an in situ forming gel formulation.

Protein aggregates have been discussed for a long time as a potential risk factor for immunogenicity in patients. Meanwhile, many research groups have investigated the immunogenicity of differently produced aggregates using in vitro or in vivo models. Despite all knowledge gained in these studies still little is known about the mechanisms of immunogenicity and the kind of protein aggregates bearing the greatest risk for immunogenicity. The choice of a suitable test model regarding the predictability of immunogenicity of protein aggregates in humans plays a major role and influences results and conclusions substantially. In this review we will provide an overview of the test models recently used for the evaluation of immunogenicity of protein aggregates; we will discuss advantages and drawbacks regarding their usability and predictive power for immunogenicity in humans.

The immunogenicity of protein aggregates has been investigated in numerous studies. Nevertheless, it is still unknown which kind of protein aggregates enhance immunogenicity the most. The ability of the currently used in vitro and in vivo systems regarding their predictability of immunogenicity in humans is often questionable, and results are partially contradictive. In this study, we used a 2D in vitro assay and a complex 3D human artificial lymph node model to predict the immunogenicity of protein aggregates of bevacizumab and adalimumab. The monoclonal antibodies were exposed to different stress conditions such as light, heat, and mechanical stress to trigger the formation of protein aggregates and particles, and samples were analyzed thoroughly. Cells and culture supernatants were harvested and analyzed for dendritic cell marker and cytokines. Our study in the artificial lymph node model revealed that bevacizumab after exposure to heat triggered a TH1- and proinflammatory immune response, whereas no trend of immune responses was seen for adalimumab after exposure to different stress conditions. The human artificial lymph node model represents a new test model for testing the immunogenicity of protein aggregates combining the relevance of a 3D human system with the rather easy handling of an in vitro setup.

In order to develop a comprehensive understanding of SFT innovation systems and processes, we analysed successful innovations, by starting our analysis with the felt need and the origins of the innovative idea, through to its implementation and diffusion. Six examples of appropriate cases were chosen in close collaboration with the practice partners of Smart-AKIS (AUA, ACTA, INTIA, ZALF and Delphy) and interactively studied the innovation processes by closely looking at key actors and their functions, and key events. We received three case studies of innovative products (trecker.com, agrivi, and arable smart sprayer) and three case studies of innovative practices (CTF in both Spain and The UK, and section controlled spraying in The Netherlands). Collaborations between innovators and farmers were key interactions throughout all phases of all innovations, and were a key supporting factor. Other supporting factors for the success of the innovations included demonstrations and field days, motivation and positive attitudes of the innovators. Hindering factors were funding at different point, technology availability and compatibility, and infrastructure.

"Three-layered micelles" (3LM) composed of two triblock copolymers, poly(L-lactide)-b-polyethyleneimine-b-poly(L-lactide) (PLLA-PEI-PLLA) and poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) (PLLA-PEG-PLLA) are designed to combine electrostatic interaction and solvent-induced condensation of DNA. The low molecular weight PLLA-PEI-PLLA is synthesized by a facile amine-protection/deprotection approach and employed as a gene vector, compacting DNA as a polyplex core in the organo-micelles. The individual organo-micelle is further encapsulated within a PLLA-PEG-PLLA amphiphilic micelle leading to an aqueous stable colloidal dispersion. The resulting spherical 3LM possess a hydrodynamic diameter of ca. 200 nm and zeta potential close to neutral and display excellent stability to competing polyanions such as dextran sulfate in neutral pH (7.4). Such high stability is attributed to the complete shielding of the PEI/DNA polyplex core with an impermeable hydrophobic intermediate layer. However, greater than 90% of the encapsulated DNA are released within 30 min when exposed to slightly acidic pH (4.5). Based on our findings, a new class of non-viral delivery system for nucleic acids with superb stability and stealth properties is identified.

This paper shows why Kant's critique of empirical psychology should not be read as a scathing criticism of quantitative scientific psychology, but has valuable lessons to teach in support of it. By analysing Kant's alleged objections in the light of his critical theory of cognition, it provides a fresh look at the problem of quantifying first-person experiences, such as emotions and sense-perceptions. An in-depth discussion of applying the mathematical principles, which are defined in the Critique of Pure Reason as the constitutive conditions for mathematical-numerical experience in general, to inner sense will demonstrate why it is in principle possible to justify a quantitative structure of psychological judgments on the grounds of Kant's critical thinking. In conclusion, it will propose how Kant's critique could be used in a constructive way to develop first steps towards a transcendental foundation of psychological knowledge.

Polymeric micelles have found a growing interest as gene vectors due to the serious safety concerns associated with viral vectors. In particular, the cationic polymer polyethylene imine (PEI) has shown relatively high condensation and transfection efficiencies. Additionally, polyethylene glycol (PEG) modification of polymeric gene vectors has dramatically improved their biological properties, including enhanced biocompatibility, prolonged circulation time, and increased bio-distribution. However, PEG grafting of PEI for subsequent condensation of nucleic acids (NAs) does not necessarily result in the formation of a PEI/NAs core with a PEG corona. But often times, the presence of PEG interferes with PEI's electrostatic interaction with NAs. We describe here a facile method to prepare multilayered biodegradable micelles which address some of the critical drawbacks associated with current PEI-based systems. The polyplex micelles have superb stability and stealth properties. Moreover, we describe a method to prepare fully biodegradable and biocompatible injectable hydrogels for use in localized gene therapy.

Polymeric micelles have found a growing interest as gene vectors due to the serious safety concerns associated with viral vectors. In particular, the cationic polymer polyethylene imine (PEI) has shown relatively high condensation and transfection efficiencies. Additionally, polyethylene glycol (PEG) modification of polymeric gene vectors has dramatically improved their biological properties, including enhanced biocompatibility, prolonged circulation time, and increased bio-distribution. However, PEG grafting of PEI for subsequent condensation of nucleic acids (NAs) does not necessarily result in the formation of a PEI/NAs core with a PEG corona. But often times, the presence of PEG interferes with PEI's electrostatic interaction with NAs. We describe here a facile method to prepare multilayered biodegradable micelles which address some of the critical drawbacks associated with current PEI-based systems. The polyplex micelles have superb stability and stealth properties. Moreover, we describe a method to prepare fully biodegradable and biocompatible injectable hydrogels for use in localized gene therapy.

Hooked apex stolons and initial swelling stolons of potato plants were treated with 3 3 10 ‐8 mol l ‐1 jasmonic acid (JA) to study the effect of this compound on histology, cell expansion and tissue differentiation. In hooked apex stolons, JA application increased the meristem thickness and reduced the length of the leaf primordia, whereas in initial swelling stolons narrowing of the apical region, absence of leaf primordia and swelling of the subapical meristem were evident. Early vascular tissue differentiation was observed in response to JA treatment, especially of xylem elements from regions proximal to the tunic. Protoxylem elements, such as tracheal elements, were present with thin primary cell walls. The cell area was measured in two zones: zone I, central mother cells situated immediately under the tunic; and zone II, rib meristem cells. JA caused a four- and six-fold increase in cell area in both zones in hooked apex stolons and initial swelling stolons, respectively. Thus, tuber formation is concluded to occur as a consequence of increased cell expansion, a reduction in the length of leaf primordia, enlargement of meristems, and early vascular tissue differentiation. a 2003 Annals of Botany Company

"Three-layered micelles" (3LM) composed of two triblock copolymers, poly(L-lactide)-b-polyethyleneimine-b-poly(L-lactide) (PLLA-PEI-PLLA) and poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) (PLLA-PEG-PLLA) are designed to combine electrostatic interaction and solvent-induced condensation of DNA. The low molecular weight PLLA-PEI-PLLA is synthesized by a facile amine-protection/deprotection approach and employed as a gene vector, compacting DNA as a polyplex core in the organo-micelles. The individual organo-micelle is further encapsulated within a PLLA-PEG-PLLA amphiphilic micelle leading to an aqueous stable colloidal dispersion. The resulting spherical 3LM possess a hydrodynamic diameter of ca. 200 nm and zeta potential close to neutral and display excellent stability to competing polyanions such as dextran sulfate in neutral pH (7.4). Such high stability is attributed to the complete shielding of the PEI/DNA polyplex core with an impermeable hydrophobic intermediate layer. However, greater than 90% of the encapsulated DNA are released within 30 min when exposed to slightly acidic pH (4.5). Based on our findings, a new class of non-viral delivery system for nucleic acids with superb stability and stealth properties is identified.

Expression of GATA-3 in female breast cancers has been linked to estrogen receptor (ER) expression and, in turn, to improved outcomes. However, GATA-3 has not been studied in male breast cancers. Nineteen male breast carcinomas (average age: 63 years) and 164 female breast carcinomas (average age: 57 years) were immunostained for GATA-3. Results were compared to age, tumor size, tumor grade, lymph node status, distant metastases, survival, and positivity for ER, progesterone receptor (PR), and HER2/neu. Six of 19 (31.6%) male and 135 of 164 (82.3%) female breast carcinomas were GATA-3 positive (P < .001). In women, 82.1% of GATA-3-positive cancers were grade 1 or 2, whereas 75.9% of GATA-3-negative cancers were grade 3 (P < .001); no such significant correlation was seen in men. Unlike female cancers, male cancers showed no correlation between GATA-3 positivity and ER positivity, PR positivity, or distant metastases. Nodal metastasis and HER2 status were not linked to GATA-3 in either sex. Seventeen (89.5%) men were alive at follow-up (average: 61 months); only 1 died of disease. Most women (159/164, 97.0%) were also alive at follow-up (average: 41 months), with a higher proportion of GATA-3-negative women dead than GATA-3-positive women (3/29 [10.3%] vs. 2/135 [1.5%], P = .039). GATA-3 is expressed less often in male than female breast cancers. Male cancers show no correlation between GATA-3 positivity and ER/PR positivity or distant metastases, unlike female cancers. There appears to be no link between GATA-3 positivity and survival in men, whereas in women, GATA-3-positive tumors are typically lower grade with a better prognosis.