The Break-in parties in Latin America: success or failure?

En esta nota de pesquisa se da cuenta del desarrollo teórico y el diseño metodológico del proyecto de investigación “Los Break-in parties en América Latina: ¿éxito o fracaso?”. La propuesta general del proyecto es: analizar las características de estos partidos capaces de “irrumpir” en el sistema de partidos; revelar cómo las condiciones estructurales del momento de la génesis inciden en el desarrollo del partido “hacia adentro” y “hacia afuera”; y establecer una explicación que vincule estos tipos de partidos, su origen y desarrollo, con su éxito o su fracaso posterior. Con base en estos objetivos, en esta nota de pesquisa se llevará a cabo: primero, una revisión bibliográfica sobre el surgimiento de nuevos partidos; segundo, una problematización sobre qué es lo “novedoso” de estas organizaciones; y tercero, una exposición de las principales decisiones teórico y metodológicas para analizar los Break-in parties.This research note outlines the theoretical development and methodological design of the research project “Break-in parties in Latin America: Success or Failure?”. The aim of the project is to analyze the characteristics of parties that manage to break into the party system – to clarify how structural conditions at the moment of genesis affect the “inward” and “outward” development of these parties and to explain how its origin and development are linked to their subsequent success or failure. To expose these objectives, in this research-note we procede as follows: first, we offer a literature review on the emergence of new parties; second, we discuss what is “new” in these kinds of organizations; and third, we explain our theoretical and methodological approach to analyze the break-in parties in Latin America.Fil: Kestler, Thomas. Universitat Wurzburg; AlemaniaFil: Krause, Silvana. Universidade Federal do Rio Grande do Sul; BrasilFil: Lucca, Juan Bautista. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

NF-κB controls the global pro-inflammatory response in endothelial cells: evidence for the regulation of a pro-atherogenic program

Activation of the transcription factor NF-κB is critical for the tumor necrosis factor-α (TNF-α)-induced inflammatory response. Here we report the complete gene expression profile from activated microvascular endothelial cells emphasizing the direct contribution of the NF-κB pathway. Human microvascular endothelial cell line-1 (HMEC-1) cells were modified to express dominant interfering mutants of the IKK/NF-κB signaling module and expression profiles were determined. Our results provide compelling evidence for the virtually absolute dependence of TNF-α-regulated genes on NF-κB. A constitutively active IKK2 was sufficient for maximal induction of most target genes, whereas a transdominant IκBα suppressed gene expression. Several genes with a critical role in atherogenesis were identified. The endothelial lipase (EL) gene, a key enzyme involved in lipoprotein metabolism, was investigated more in detail. Binding sites interacting with NF-κB in vitro and in vivo were identified and co-transfection experiments demonstrated the direct regulation of the EL promoter by NF-κB. We conclude that targeting the IKK/NF-κB pathway or specific genes downstream may be effective for the control or prevention of chronic inflammatory diseases such as atherosclerosis

Los Break-in parties en América Latina: éxito o fracaso?

This research note outlines the theoretical development and methodological design of the research project “Break-in parties in Latin America: Success or Failure?”. The aim of the project is to analyze the characteristics of parties that manage to break into the party system – to clarify how structural conditions at the moment of genesis affect the “inward” and “outward” development of these parties and to explain how its origin and development are linked to their subsequent success or failure. To expose these objectives, in this research-note we procede as follows: first, we offer a literature review on the emergence of new parties; second, we discuss what is “new” in these kinds of organizations; and third, we explain our theoretical and methodological approach to analyze the break-in parties in Latin America.En esta nota de pesquisa se da cuenta del desarrollo teórico y el diseño metodológico del proyecto de investigación “Los Break-in parties en América Latina: ¿éxito o fracaso?”. La propuesta general del proyecto es: analizar las características de estos partidos capaces de “irrumpir” en el sistema de partidos; revelar cómo las condiciones estructurales del momento de la génesis inciden en el desarrollo del partido “hacia adentro” y “hacia afuera”; y establecer una explicación que vincule estos tipos de partidos, su origen y desarrollo, con su éxito o su fracaso posterior. Con base en estos objetivos, en esta nota de pesquisa se llevará a cabo: primero, una revisión bibliográfica sobre el surgimiento de nuevos partidos; segundo, una problematización sobre qué es lo “novedoso” de estas organizaciones; y tercero, una exposición de las principales decisiones teórico y metodológicas para analizar los Break-in parties

Measuring Mental Effort for Creating Mobile Data Collection Applications

To deal with drawbacks of paper-based data collection procedures, the QuestionSys approach empowers researchers with none or little programming knowledge to flexibly configure mobile data collection applications on demand. The mobile application approach of QuestionSys mainly pursues the goal to mitigate existing drawbacks of paper-based collection procedures in mHealth scenarios. Importantly, researchers shall be enabled to gather data in an efficient way. To evaluate the applicability of QuestionSys, several studies have been carried out to measure the efforts when using the framework in practice. In this work, the results of a study that investigated psychological insights on the required mental effort to configure the mobile applications are presented. Specifically, the mental effort for creating data collection instruments is validated in a study with N=80 participants across two sessions. Thereby, participants were categorized into novices and experts based on prior knowledge on process modeling, which is a fundamental pillar of the developed approach. Each participant modeled 10 instruments during the course of the study, while concurrently several performance measures are assessed (e.g., time needed or errors). The results of these measures are then compared to the self-reported mental effort with respect to the tasks that had to be modeled. On one hand, the obtained results reveal a strong correlation between mental effort and performance measures. On the other, the self-reported mental effort decreased significantly over the course of the study, and therefore had a positive impact on measured performance metrics. Altogether, this study indicates that novices with no prior knowledge gain enough experience over the short amount of time to successfully model data collection instruments on their own. Therefore, QuestionSys is a helpful instrument to properly deal with large-scale data collection scenarios like clinical trials

Significantly improved precision of cell migration analysis in time-lapse video microscopy through use of a fully automated tracking system

<p>Abstract</p> <p>Background</p> <p>Cell motility is a critical parameter in many physiological as well as pathophysiological processes. In time-lapse video microscopy, manual cell tracking remains the most common method of analyzing migratory behavior of cell populations. In addition to being labor-intensive, this method is susceptible to user-dependent errors regarding the selection of "representative" subsets of cells and manual determination of precise cell positions.</p> <p>Results</p> <p>We have quantitatively analyzed these error sources, demonstrating that manual cell tracking of pancreatic cancer cells lead to mis-calculation of migration rates of up to 410%. In order to provide for objective measurements of cell migration rates, we have employed multi-target tracking technologies commonly used in radar applications to develop fully automated cell identification and tracking system suitable for high throughput screening of video sequences of unstained living cells.</p> <p>Conclusion</p> <p>We demonstrate that our automatic multi target tracking system identifies cell objects, follows individual cells and computes migration rates with high precision, clearly outperforming manual procedures.</p

Peripheral cytokine levels differ by HPV status and change treatment-dependently in patients with head and neck squamous cell carcinoma

Cytokines and immune mediators play an important role in the communication between immune cells guiding their response to infectious diseases or cancer. In this study, a comprehensive longitudinal analysis of serum cytokines and immune mediators in head and neck squamous cell carcinoma (HNSCC) patients was performed. In a prospective, non-interventional, longitudinal study, blood samples from 22 HNSCC patients were taken at defined time points (TP) before, during, and every 3 months after completion of (chemo)radio)therapy (CRT/RT) until 12 months after treatment. Serum concentrations of 17 cytokines/immune mediators and High-Mobility-Group-Protein B1 (HMGB1) were measured by fluorescent bead array and ELISA. Concentrations of sFas were significantly elevated during and after CRT/RT, whereas perforin levels were significantly decreased after CRT/RT. Levels of MIP-1β and Granzyme B differed significantly during CRT/RT by HPV status. Increased HMGB1 levels were observed at recurrence, accompanied by high levels of IL-4 and IL-10. The sFas increase and simultaneous perforin decrease may indicate an impaired immune cell function during adjuvant radiotherapy. Increased levels of pro-inflammatory cytokines in HPV+ compared to HPV− patients seem to reflect the elevated immunogenicity of HPV-positive tumors. High levels of HMGB1 and anti-inflammatory cytokines at recurrence may be interpreted as a sign of immune evasion

Prospective longitudinal study of immune checkpoint molecule (ICM) expression in immune cell subsets during curative conventional therapy of head and neck squamous cell carcinoma (HNSCC)

Programmed-death-1 (PD1) antibodies are approved for recurrent and metastatic head and neck squamous cell carcinoma. Multiple drugs targeting costimulatory and coinhibitory immune checkpoint molecules (ICM) have been discovered. However, it remains unknown how these ICM are affected by curative conventional therapy on different immune cell subsets during the course of treatment. In the prospective noninterventional clinical study titled “Immune Response Evaluation to Curative conventional Therapy” (NCT03053661), 22 patients were prospectively enrolled. Blood samples were drawn at defined time points throughout curative conventional treatment and follow-up. Immune cells (IC) from the different time points were assessed by multicolor flow cytometry. The following ICM were measured by flow cytometry: PD1, CTLA4, BTLA, CD137, CD27, GITR, OX40, LAG3 and TIM3. Dynamics of ICM expression were assessed using nonparametric paired samples tests. Significant changes were noted for PD1, BTLA and CD27 on multiple IC types during or after radiotherapy. Nonsignificant trends for increased expression of OX40 and GITR from baseline until the end of RT were observed on CD4 T cells and CD4+ CD39+ T cells. In patients with samples at recurrence of disease, a nonsignificant increase of TIM3 and LAG3 positive CD4+ CD39+ T cells was evident, accompanied by an increase of double positive cells for TIM3/LAG3. Potential future targets to be combined with RT in the conventional treatment and anti-PD1/PD-L could be BTLA agonists, or agonistic antibodies to costimulatory ICM like CD137, OX40 or GITR. The combination of cetuximab with CD27 agonistic antibodies enhancing ADCC or the targeting of TIM3/LAG3 may be another promising strategy