939 resultados para Concept development


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We propose a slow-wave MEMS phase shifter that can be fabricated using the CMOS back-end and an additional maskless post-process etch. The tunable phase shifter concept is formed by a conventional slow-wave transmission line. The metallic ribbons that form the patterned floating shield of this type of structure are released to allow motion when a control voltage is applied, which changes the characteristic impedance and the phase velocity. For this device a quality factor greater than 40 can be maintained, resulting in a figure of merit on the order of 0.7 dB/360 degrees and a total area smaller than 0.14 mm(2) for a 60-GHz working frequency. (C) 2011 Elsevier B.V. All rights reserved.

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Abstract Background From shotgun libraries used for the genomic sequencing of the phytopathogenic bacterium Xanthomonas axonopodis pv. citri (XAC), clones that were representative of the largest possible number of coding sequences (CDSs) were selected to create a DNA microarray platform on glass slides (XACarray). The creation of the XACarray allowed for the establishment of a tool that is capable of providing data for the analysis of global genome expression in this organism. Findings The inserts from the selected clones were amplified by PCR with the universal oligonucleotide primers M13R and M13F. The obtained products were purified and fixed in duplicate on glass slides specific for use in DNA microarrays. The number of spots on the microarray totaled 6,144 and included 768 positive controls and 624 negative controls per slide. Validation of the platform was performed through hybridization of total DNA probes from XAC labeled with different fluorophores, Cy3 and Cy5. In this validation assay, 86% of all PCR products fixed on the glass slides were confirmed to present a hybridization signal greater than twice the standard deviation of the deviation of the global median signal-to-noise ration. Conclusions Our validation of the XACArray platform using DNA-DNA hybridization revealed that it can be used to evaluate the expression of 2,365 individual CDSs from all major functional categories, which corresponds to 52.7% of the annotated CDSs of the XAC genome. As a proof of concept, we used this platform in a previously work to verify the absence of genomic regions that could not be detected by sequencing in related strains of Xanthomonas.

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Abstract Background Tobacco and cannabis use are strongly interrelated, but current national and international cessation programs typically focus on one substance, and address the other substance either only marginally or not at all. This study aimed to identify the demand for, and describe the development and content of, the first integrative group cessation program for co-smokers of cigarettes and cannabis. Methods First, a preliminary study using expert interviews, user focus groups with (ex-)smokers, and an online survey was conducted to investigate the demand for, and potential content of, an integrative smoking cessation program (ISCP) for tobacco and cannabis co-smokers. This study revealed that both experts and co-smokers considered an ISCP to be useful but expected only modest levels of readiness for participation.Based on the findings of the preliminary study, an interdisciplinary expert team developed a course concept and a recruitment strategy. The developed group cessation program is based on current treatment techniques (such as motivational interviewing, cognitive behavioural therapy, and self-control training) and structured into six course sessions.The program was evaluated regarding its acceptability among participants and course instructors. Results Both the participants and course instructors evaluated the course positively. Participants and instructors especially appreciated the group discussions and the modules that were aimed at developing personal strategies that could be applied during simultaneous cessation of tobacco and cannabis, such as dealing with craving, withdrawal, and high-risk situations. Conclusions There is a clear demand for a double cessation program for co-users of cigarettes and cannabis, and the first group cessation program tailored for these users has been developed and evaluated for acceptability. In the near future, the feasibility of the program will be evaluated. Trial registration Current Controlled Trials ISRCTN15248397

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Introduction: Endometrial decidualization and associated extracellular matrix (ECM) remodeling are critical events to the establishment of the maternal-fetal interface and successful pregnancy. Here, we investigated the impact of type 1 diabetes on these processes during early embryonic development, in order to contribute to the understanding of the maternal factors associated to diabetic embryopathies. Methods: Alloxan-induced diabetic Swiss female mice were bred after different periods of time to determine the effects of diabetes progression on the development of gestational complications. Furthermore, the analyses focused on decidual development as well as mRNA expression, protein deposition and ultrastructural organization of decidual ECM. Results: Decreased number of implantation sites and decidual dimensions were observed in the group mated 90-110 days after diabetes induction (D), but not in the 50-70D group. Picrosirius staining showed augmentation in the fibrillar collagen network in the 90e110D group and, following immunohistochemical examination, that this was associated with increase in types I and V collagens and decrease in type III collagen and collagen-associated proteoglycans biglycan and lumican. qPCR, however, demonstrated that only type I collagen mRNA levels were increased in the diabetic group. Alterations in the molecular ratio among distinct collagen types and proteoglycans were associated with abnormal collagen fibrillogenesis, analyzed by transmission electron microscopy. Conclusions: Our results support the concept that the development of pregnancy complications is directly related with duration of diabetes (progression of the disease), and that this is a consequence of both systemic factors (i.e. disturbed maternal endocrine-metabolic profile) and uterine factors, including impaired decidualization and ECM remodeling

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The present thesis treats the issue of gender equality in Macedonia during the period of transition from the socialist system to the one of parliamentary democracy. The main aim is to mainstream the gender perspective in the analysis of the transitional policies through the examination of the basic citizenship rights to which citizens are entitled and by the means of the evaluation of their capabilities to exercise these rights. Gender equality, as one of the main strongholds of the concept of human development is measured through the application of nine gender relevant capabilities in a Case study conducted within selected municipalities in the country. Through the analysis of the Macedonian constitutional and legal framework and the assessment of gender based inequalities, the research questions the need for the enactment of a process of engendering of citizenship, which would integrate gender based differences, contemplate the private sphere of citizens lives and pledge participation in the political life of the country. The thesis, finally, analyses the gender equality strategy of the Macedonian government with the purpose to evaluate whether it is context based, i.e. it tackles the main fields where inequalities emerge and in this context whether it envisages a process of engendering of citizenship.

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The research activity carried out during the PhD course in Electrical Engineering belongs to the branch of electric and electronic measurements. The main subject of the present thesis is a distributed measurement system to be installed in Medium Voltage power networks, as well as the method developed to analyze data acquired by the measurement system itself and to monitor power quality. In chapter 2 the increasing interest towards power quality in electrical systems is illustrated, by reporting the international research activity inherent to the problem and the relevant standards and guidelines emitted. The aspect of the quality of voltage provided by utilities and influenced by customers in the various points of a network came out only in recent years, in particular as a consequence of the energy market liberalization. Usually, the concept of quality of the delivered energy has been associated mostly to its continuity. Hence the reliability was the main characteristic to be ensured for power systems. Nowadays, the number and duration of interruptions are the “quality indicators” commonly perceived by most customers; for this reason, a short section is dedicated also to network reliability and its regulation. In this contest it should be noted that although the measurement system developed during the research activity belongs to the field of power quality evaluation systems, the information registered in real time by its remote stations can be used to improve the system reliability too. Given the vast scenario of power quality degrading phenomena that usually can occur in distribution networks, the study has been focused on electromagnetic transients affecting line voltages. The outcome of such a study has been the design and realization of a distributed measurement system which continuously monitor the phase signals in different points of a network, detect the occurrence of transients superposed to the fundamental steady state component and register the time of occurrence of such events. The data set is finally used to locate the source of the transient disturbance propagating along the network lines. Most of the oscillatory transients affecting line voltages are due to faults occurring in any point of the distribution system and have to be seen before protection equipment intervention. An important conclusion is that the method can improve the monitored network reliability, since the knowledge of the location of a fault allows the energy manager to reduce as much as possible both the area of the network to be disconnected for protection purposes and the time spent by technical staff to recover the abnormal condition and/or the damage. The part of the thesis presenting the results of such a study and activity is structured as follows: chapter 3 deals with the propagation of electromagnetic transients in power systems by defining characteristics and causes of the phenomena and briefly reporting the theory and approaches used to study transients propagation. Then the state of the art concerning methods to detect and locate faults in distribution networks is presented. Finally the attention is paid on the particular technique adopted for the same purpose during the thesis, and the methods developed on the basis of such approach. Chapter 4 reports the configuration of the distribution networks on which the fault location method has been applied by means of simulations as well as the results obtained case by case. In this way the performance featured by the location procedure firstly in ideal then in realistic operating conditions are tested. In chapter 5 the measurement system designed to implement the transients detection and fault location method is presented. The hardware belonging to the measurement chain of every acquisition channel in remote stations is described. Then, the global measurement system is characterized by considering the non ideal aspects of each device that can concur to the final combined uncertainty on the estimated position of the fault in the network under test. Finally, such parameter is computed according to the Guide to the Expression of Uncertainty in Measurements, by means of a numeric procedure. In the last chapter a device is described that has been designed and realized during the PhD activity aiming at substituting the commercial capacitive voltage divider belonging to the conditioning block of the measurement chain. Such a study has been carried out aiming at providing an alternative to the used transducer that could feature equivalent performance and lower cost. In this way, the economical impact of the investment associated to the whole measurement system would be significantly reduced, making the method application much more feasible.

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The research undertaken for this doctoral thesis explores the issue of teachers professionalism within pre-school institutions. The issue of early childhood professionalism has become increasingly important in the academic debate over the last decade as it is documented by a growing body of research published on the topic both nationally (Contini & Manini, 2007; Bondioli & Ferrari, 2004) and internationally (Peeters, 2008; Urban & Dalli, 2008; Urban, 2010). The study presented in this thesis aims at investigating teachers’ conceptualisations of professionalism by focusing on their understandings of educational work. The idea standing at the core of this research is that exploring the concept of professionalism from a ground-up perspective could lead to important reflections for a re-conceptualisation of professional development as a space for change directed from within institutions. The study is framed within a broadly sociological concern that inform the data analysis by contextualising the issue of early childhood professionalism in the contemporary socio-political arena. The research involves sixty teachers operating in state, municipal and private pre-school institutions located in Bologna province that took part to focus groups and interviews. The empirical materials, consisting of oral and written statements, are interpreted through phenomenographical analysis that gives account of how features of professionalism vary across the different institutional settings in which they are played out. This thesis, written in English and informed by an European research background, offers a contribution to the furthering of systemic approaches to the investigation of early childhood education professionalism in the context of the national and international academic debate.

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In the frame of EU rural policy, always more oriented towards environmental concerns and green livelihoods, Romania stands out for the predominance of rural areas and high nature value farming. The country has to face the challenge of joining the modernization process of rural farming systems with the valorization of local assets. Tourism has emerged as one of the main drivers of change and contributors for a sustainable exploitation of local resources. Rural tourism (RT) can foster the enhancement of the territorial capital (TC), the preservation of public goods (PGs) and the promotion of a more environmental oriented livelihood. The research focuses on a case study area, two valleys from Maramureş, where environmental approaches as diversification strategies are partially explored. The work investigates the role of tourism initiatives for the promotion of green oriented practices. The first part of the work is based on a literature review and interdisciplinary analysis of secondary data to identify the key issues: from rural development policy, to the concept of TC, of PGs and RT. The Romanian development programmes and related strategies are investigated; afterwards the characteristics of the County and the role of RT as diversification and valorisation policies is considered. The second part is based on the collection of primary data through interviews to different local stakeholders (farmers owners of rural guesthouses, local administrators, networks and artisans). The main frequencies are analyzed, a cluster analysis is computed to evaluate the similarities within the most representative groups and a comparative analysis is carried out between the two Valleys. The frame of the analysis is based on a set of indicators following the dimensions of the TC, to assess the characteristics of the local stakeholders and to outline the perception about the local PGs and on the adopted strategies to manage the territory. Final considerations are elaborated and few scenarios are outlined, giving relevance to the importance of improving awareness and creating embeddedness among public-private local stakeholders and resources as a tool for a socio-economic and environmental development of the area.

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This collection of essays examines various aspects of regional development and the issues of internationalization. The first essay investigates the implications of the impressive growth of China from a rural-urban perspective and addresses the topic of convergence in China by employing a non-parametrical approach to study the distribution dynamics of per capita income at province, rural and urban levels. To better understand the degree of inequality characterizing China and the long-term predictions of convergence or divergence of its different territorial aggregations, the second essay formulates a composite indicator of Regional Development (RDI) to benchmark development at province and sub-province level. The RDI goes beyond the uni-dimensional concept of development, generally proxied by the GDP per capita, and gives attention to the rural-urban dimension. The third essay “Internationalization and Trade Specialization in Italy. The role of China in the international intra-firm trade of the Italian regions” - deals with another aspect of regional economic development: the progressive de-industrialisation and de-localization of the local production. This essay looks at the trade specialization of selected Italian regions (those regions specialized in manufacturing) and the fragmentation of the local production on a global scale. China represents in this context an important stakeholder and the paper documents the importance of this country in the regional intra-firm trade.

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The main concern of the A4 parity violation experiment at the Mainzer Microtron accelerator facility is to study the electric and magnetic contributions of strange quarks to the charge and magnetism of the nucleons at the low momentum transfer region. More precisely, the A4 collaboration investigates the strange quarks' contribution to the electric and magnetic vector form factors of the nucleons. Thus, it is important that the A4 experiment uses an adequate and precise non-destructive online monitoring tool for the electron beam polarization when measuring single spin asymmetries in elastic scattering of polarized electrons from unpolarized nucleons. As a consequence, the A4 Compton backscattering polarimeter was designed and installed such that we can take the absolute measurement of the electron beam polarization without interruption to the parity violation experiment. The present study shows the development of an electron beam line that is called the chicane for the A4 Compton backscattering polarimeter. The chicane is an electron beam transport line and provides an interaction region where the electron beam and the laser beam overlap. After studying the properties of beam line components carefully, we developed an electron beam control system that makes a beam overlap between the electron beam and the laser beam. Using the system, we can easily achieve the beam overlap in a short time. The electron control system, of which the performance is outstanding, is being used in production beam times. And the study presents the development of a scintillating fiber electron detector that reduces the statistical error in the electron polarization measurement. We totally redesigned the scintillating fiber detector. The data that were taken during a 2008 beam time shows a huge background suppression, approximately 80 percent, while leaving the Compton spectra almost unchanged when a coincidence between the fiber detector and the photon detector is used. Thus, the statistical error of the polarization measurement is reduced by about 40 percent in the preliminary result. They are the significant progress in measuring a degree of polarization of the electron beam.

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The present thesis is concerned with the development of novel cocaine-derived dopamine transporter ligands for the non-invasive exploration of the striatal and extra-striatal dopamine transporter (DAT) in living systems. The presynaptic dopamine transporter acquires an important function within the mediation of dopaminergic signal transduction. Its availability can serve as a measure for the overall integrity of the dopaminergic system. The DAT is upregulated in early Parkinson’s disease (PD), resulting in an increased availability of DAT-binding sites in the striatal DAT domains. Thereby, DAT imaging has become an important routine diagnostic tool for the early diagnosis of PD in patients, as well as for the differentiation of PD from symptomatically similar medical conditions. Furthermore, the dopaminergic system is involved in a variety of psychiatric diseases. In this regard, DAT-selective imaging agents may provide detailed insights into the scientific understanding of the biochemical background of both, the progress as well as the origins of the symptoms. DAT-imaging may also contribute to the determination of the dopaminergic therapeutic response for a given medication and thereby contribute to more convenient conditions for the patient. From an imaging point of view, the former demands a high availability of the radioactive probe to facilitate broad application of the modality, whereas the latter profits from short-lived probes, suitable for multi-injection studies. Therefore, labelling with longer-lived 18F-fluoride and in particular the generator nuclide 68Ga is worthwhile for clinical routine imaging. In contrast, the introduction of a 11C-label is a prerequisite for detailed scientific studies of neuronal interactions. The development of suitable DAT-ligands for medical imaging has often been complicated by the mixed binding profile of many compounds that that interact with the DAT. Other drawbacks have included high non-specific binding, extensive metabolism and slow accumulation in the DAT-rich brain areas. However, some recent examples have partially overcome the mentioned complications. Based on the structural speciality of these leads, novel ligand structures were designed and successfully synthesised in the present work. A structure activity relationship (SAR) study was conducted wherein the new structural modifications were examined for their influence on DAT-affinity and selectivity. Two of the compounds showed improvements in in vitro affinity for the DAT as well as selectivity versus the serotonin transporter (SERT) and norepinephrine transporter (NET). The main effort was focussed on the high-affinity candidate PR04.MZ, which was subsequently labelled with 18F and 11C in high yield. An initial pharmacological characterisation of PR04.MZ in rodents revealed highly specific binding to the target brain structures. As a result of low non-specific binding, the DAT-rich striatal area was clearly visualised by autoradiography and µPET. Furthermore, the radioactivity uptake into the DAT-rich brain regions was rapid and indicated fast binding equilibrium. No radioactive metabolite was found in the rat brain. [18F]PR04.MZ and [11C]PR04.MZ were compared in the primate brain and the plasma metabolism was studied. It was found that the ligands specifically visualise the DAT in high and low density in the primate brain. The activity uptake was rapid and quantitative evaluation by Logan graphical analysis and simplified reference tissue model was possible after a scanning time of 30 min. These results further reflect the good characteristics of PR04.MZ as a selective ligand of the neuronal DAT. To pursue 68Ga-labelling of the DAT, initial synthetic studies were performed as part of the present thesis. Thereby, a concept for the convenient preparation of novel bifunctional chelators (BFCs) was developed. Furthermore, the suitability of novel 1,4,7-triazacyclononane based N3S3-type BFCs for biomolecule-chelator conjugates of sufficient lipophilicity for the penetration of the blood-brain-barrier was elucidated.

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The times following international or civil conflicts but also violent revolutions often come with unequal share of the peace dividend for men and women. Delusions for women who gained freedom of movement and of roles during conflict but had to step back during reconstruction and peace have been recorded in all regions of the world. The emergence of peacebuilding as a modality for the international community to ensure peace and security has slowly incorporated gender sensitivity at the level of legal and policy instruments. Focusing on Rwanda, a country that has obtained significant gender advancement in the years after the genocide while also obtaining to not relapse into conflict, this research explores to what extent the international community has contributed to this transformation. From a review of evaluations, findings are that many of the interventions did not purse gender equality, and overall the majority understood gender and designed actions is a quite superficial way which would hardly account for the significative advancement in combating gender discrimination that the Government, for its inner political will, is conducting. Then, after a critique from a feminist standpoint to the concept of human security, departing from the assumption (sustained by the Governemnt of Rwanda as well) that domestic violence is a variable influencing level of security relevant at the national level, a review of available secondary data on GBV is conducted an trends over the years analysed. The emerging trends signal a steep increase in prevalence of GBV and in domestic violence in particular. Although no conclusive interpretation can be formulated on these data, there are elements suggesting the increase might be due to augmented reporting. The research concludes outlining possible further research pathways to better understand the link in Rwanda between the changing gender norms and the GBV.

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Beside the traditional paradigm of "centralized" power generation, a new concept of "distributed" generation is emerging, in which the same user becomes pro-sumer. During this transition, the Energy Storage Systems (ESS) can provide multiple services and features, which are necessary for a higher quality of the electrical system and for the optimization of non-programmable Renewable Energy Source (RES) power plants. A ESS prototype was designed, developed and integrated into a renewable energy production system in order to create a smart microgrid and consequently manage in an efficient and intelligent way the energy flow as a function of the power demand. The produced energy can be introduced into the grid, supplied to the load directly or stored in batteries. The microgrid is composed by a 7 kW wind turbine (WT) and a 17 kW photovoltaic (PV) plant are part of. The load is given by electrical utilities of a cheese factory. The ESS is composed by the following two subsystems, a Battery Energy Storage System (BESS) and a Power Control System (PCS). With the aim of sizing the ESS, a Remote Grid Analyzer (RGA) was designed, realized and connected to the wind turbine, photovoltaic plant and the switchboard. Afterwards, different electrochemical storage technologies were studied, and taking into account the load requirements present in the cheese factory, the most suitable solution was identified in the high temperatures salt Na-NiCl2 battery technology. The data acquisition from all electrical utilities provided a detailed load analysis, indicating the optimal storage size equal to a 30 kW battery system. Moreover a container was designed and realized to locate the BESS and PCS, meeting all the requirements and safety conditions. Furthermore, a smart control system was implemented in order to handle the different applications of the ESS, such as peak shaving or load levelling.

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With this dissertation research we investigate intersections between design and marketing and in this respect, which factors do contribute that a product design becomes brand formative. We have developed a Brand Formative Design (BFD) framework, which investigates individual design features in a holistic, comparable, brand relevant, and consumer specific context. We discuss what kinds of characteristics contribute to BFD but also illuminate how they should be applied and examine: rnA holistic framework leading to Brand Formative Design. Identification and assessment of BFD Drivers. The dissection of products into three Distinctive Design Levels. The detection of surprising design preferences. The appropriate degree of scheme deviation with evolutionary design. Simulated BFD development processes with three different products and the integration of consumers. Future oriented objectification, comparability and assessment of design. Recommendations for the management of design in a brand specific context. Design is a product feature, which contributes significantly to the success of products. However, the development of new design contains challenges. Design can hardly be objectified; many people have an opinion concerning the attractiveness of new products but cannot formulate their future preferences. Product design is widely developed based on intuition, which can be difficult for the management of design. Here the concept of Brand Formative Design can provide a framework which contributes to structure, objectify, develop and assess new evolutionary design in brand and future relevant contexts, but also integrates consumers and their preferences without restricting creativity too much.

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Due to multiple immune evasion mechanisms of cancer cells, novel therapy approaches are required to overcome the limitations of existing immunotherapies. Bispecific antibodies are potent anti-cancer drugs, which redirect effector T cells for specific tumor cell lysis, thus enabling the patient’s immune system to fight cancer cells. The antibody format used in this proof of concept study–bispecific ideal monoclonal antibodies termed BiMAB–is a tailor-made recombinant protein, which consists of two fused scFv antibodies recognizing different antigens. Both are arranged in tandem on a single peptide chain and the individual variable binding domains are separated by special non-immunogenic linkers. The format is comprised of a scFv targeting CLDN18.2–a gastric cancer tumor associated antigen (TAA) –while the second specificity binds the CD3 epsilon (CD3ε) subunit of the T cell receptor (TCR) on T cells. For the first time, we compared in our IMAB362-based BiMAB setting, four different anti-CD3-scFvs, respectively derived from the mAbs TR66, CLB-T3, as well as the humanized and the murine variant of UCHT1. In addition, we investigated the impact of an N- versus a C-terminal location of the IMAB362-derived scFv and the anti-CD3-scFvs. Thus, nine CLDN18.2 specific BiMAB proteins were generated, of which all showed a remarkably high cytotoxicity towards CLDN18.2-positive tumor cells. Because of its promising effectiveness, 1BiMAB emerged as the BiMAB prototype. The selectivity of 1BiMAB for its TAA and CD3ε, with affinities in the nanomolar range, has been confirmed by in vitro assays. Its dual binding depends on the design of an N-terminally positioned IMAB362 scFv and the consecutive C-terminally positioned TR66 scFv. 1BiMAB provoked a concentration and target cell dependent T cell activation, proliferation, and upregulation of the cytolytic protein Granzyme B, as well as the consequent elimination of target cells. Our results demonstrate that 1BiMAB is able to activate T cells independent of elements that are usually involved in the T cell recognition program, like antigen presentation, MHC restriction, and co-stimulatory effector molecules. In the first in vivo studies using a subcutaneous xenogeneic tumor mouse model in immune incompetent NSG mice, we could prove a significant therapeutic effect of 1BiMAB with partial or complete tumor elimination. The initial in vitro RIBOMAB experiments correspondingly showed encouraging results. The electroporation of 1BiMAB IVT-RNA into target or effector cells was feasible, while the functionality of translated 1BiMAB was proven by induced T cell activation and target cell lysis. Accordingly, we could show that the in vitro RIBOMAB approach was applicable for all nine BiMABs, which proves the RIBOMAB concept. Thus, the CLDN18.2-BiMAB strategy offers great potential for the treatment of cancer. In the future, administered either as protein or as IVT-RNA, the BiMAB format will contribute towards finding solutions to raise and sustain tumor-specific cellular responses elicited by engaged and activated endogenous T cells. This will potentially enable us to overcome immune evasion mechanisms of tumor cells, consequently supporting current solid gastric cancer therapies.