Rapid response to pandemic threats: immunogenic epitope detection of pandemic pathogens for diagnostics and vaccine development using peptide microarrays

Emergence and re-emergence of pathogens bearing the risk of becoming a pandemic threat are on the rise. Increased travel and trade, growing population density, changes in urbanization, and climate have a critical impact on infectious disease spread. Currently, the world is confronted with the emergence of a novel coronavirus SARS-CoV-$_{2}$, responsible for yet more than 800 000 deaths globally. Outbreaks caused by viruses, such as SARS-CoV-$_{2}$, HIV, Ebola, influenza, and Zika, have increased over the past decade, underlining the need for a rapid development of diagnostics and vaccines. Hence, the rational identification of biomarkers for diagnostic measures on the one hand, and antigenic targets for vaccine development on the other, are of utmost importance. Peptide microarrays can display large numbers of putative target proteins translated into overlapping linear (and cyclic) peptides for a multiplexed, high-throughput antibody analysis. This enabled for example the identification of discriminant/diagnostic epitopes in Zika or influenza and mapping epitope evolution in natural infections versus vaccinations. In this review, we highlight synthesis platforms that facilitate fast and flexible generation of high-density peptide microarrays. We further outline the multifaceted applications of these peptide array platforms for the development of serological tests and vaccines to quickly encounter pandemic threats

Mobility choices - an instrument for precise automatized travel behavior detection & analysis

Within the Mobility Choices (MC) project we have developed an app that allows users to record their travel behavior and encourages them to try out new means of transportation that may better fit their preferences. Tracks explicitly released by the users are anonymized and can be analyzed by authorized institutions. For recorded tracks, the freely available app automatically determines the segments with their transportation mode; analyzes the track according to the criteria environment, health, costs, and time; and indicates alternative connections that better fit the criteria, which can individually be configured by the user. In the second step, the users can edit their tracks and release them for further analysis by authorized institutions. The system is complemented by a Web-based analysis program that helps authorized institutions carry out specific evaluations of traffic flows based on the released tracks of the app users. The automatic transportation mode detection of the system reaches an accuracy of 97%. This requires only minimal corrections by the user, which can easily be done directly in the app before releasing a track. All this enables significantly more accurate surveys of transport behavior than the usual time-consuming manual (non-automated) approaches, based on questionnaires

Computational Modeling Reveals Distinct Effects of HIV and History of Drug Use on Decision-Making Processes in Women

Objective: Drug users and HIV-seropositive individuals often show deficits in decision-making; however the nature of these deficits is not well understood. Recent studies have employed computational modeling approaches to disentangle the psychological processes involved in decision-making. Although such approaches have been used successfully with a number of clinical groups including drug users, no study to date has used computational modeling to examine the effects of HIV on decision-making. In this study, we use this approach to investigate the effects of HIV and drug use on decision making processes in women, who remain a relatively understudied population. Method: Fifty-seven women enrolled in the Women’s Interagency HIV Study (WIHS) were classified into one of four groups based on their HIV status and history of crack cocaine and/or heroin drug use (DU): HIV+/DU+ (n = 14); HIV+/DU2 (n = 17); HIV2/DU+ (n = 14); and HIV2/DU2 (n = 12). We measured decision-making with the Iowa Gambling Task (IGT) and examined behavioral performance and model parameters derived from the best-fitting computational model of the IGT. Results: Although groups showed similar behavioral performance, HIV and DU exhibited differential relationship to model parameters. Specifically, DU was associated with compromised learning/memory and reduced loss aversion, whereas HIV was associated with reduced loss aversion, but was not related to other model parameters. Conclusions: Results reveal that HIV and DU have differential associations with distinct decision-making processes in women. This study contributes to a growing line of literature which shows that different psychological processes may underlie similar behavioral performance in various clinical groups and may be associated with distinct functional outcomes

Control of Leukocyte Trafficking by Stress-Associated Hormones

Leukocyte migration is a crucial process in both homeostatic and inflammatory conditions. The spatiotemporal distribution of immune cells is balanced between processes of cellular mobilization into the bloodstream, their adhesion to vascular beds and trafficking into tissues. Systemic regulation of leukocyte mobility is achieved by different signals including neuronal and hormonal cues, of which the catecholamines and glucocorticoids have been most extensively studied. These hormones are often associated with a stress response, however they regulate immune cell trafficking also in steady state, with effects dependent upon cell type, location, time-of-day, concentration, and duration of signal. Systemic administration of catecholamines, such as the sympathetic neurotransmitters adrenaline and noradrenaline, increases neutrophil numbers in the bloodstream but has different effects on other leukocyte populations. In contrast, local, endogenous sympathetic tone has been shown to be crucial for dynamic daily changes in adhesion molecule expression in the bone marrow and skeletal muscle, acting as a key signal to the endothelium and stromal cells to regulate immune cell trafficking. Conversely, glucocorticoids are often reported as anti-inflammatory, although recent data shows a more complex role, particularly under steady-state conditions. Endogenous changes in circulating glucocorticoid concentration induce redistribution of cells and potentiate inflammatory responses, and in many paradigms glucocorticoid action is strongly influenced by time of day. In this review, we discuss the current knowledge of catecholamine and glucocorticoid regulation of leukocyte migration under homeostatic and stimulated conditions

Dimensionen digitaler Mündigkeit und politische Beteiligung im Netz

Die Forschung zur digitalen Spaltung (Digital Divide) oder auch Beteiligungsspaltung (Participation Divide) hat diverse Voraussetzungen einer partizipativen Internetnutzung untersucht. Im Mittelpunkt steht dabei eine immer größere Vielzahl förderlicher "Literacies" oder Kompetenzen. Um einer zunehmenden Unübersichtlichkeit dieses Forschungsfelds entgegenzutreten, haben erste konzeptionelle Studien das umfassendere Konzept der "digitalen Mündigkeit" vorgeschlagen. Basierend auf einer interdisziplinären Literaturanalyse erarbeitet der vorliegende Beitrag eine Definition der "digitalen Mündigkeit", und führt das Konzept durch eine entsprechende Operationalisierung erstmals einer empirischen Analyse zu. Basierend auf einer Befragung von 1.044 deutschen Internetnutzenden wird der Einfluss der digitalen Mündigkeit - neben soziodemographischen Faktoren, politischer Orientierung und Regierungsvertrauen - auf die politische Online-Beteiligung untersucht

LIGHTNING IMPULSE MODELING AND SIMULATION OF DRY-TYPE AND OIL-IMMERSED POWER- AND DISTRIBUTION TRANSFORMERS

This paper presents in detail numerical methods and techniques for lightning impulse (LI) modeling and simulation of power and distribution transformers. The modeling methods are based on equivalent circuits of transformer winding entities resulting from the initial winding discretization determined by the required accuracy. The parameters of the equivalent circuit such as resistances and self- and mutual capacitances and inductances are obtained from field simulations (FEM). The circuit equations of the transformer’s equivalent circuit written in the state space form yield a large system of differential equations that is solved in time-domain by using the standard Runge-Kutta numerical integration technique. The obtained solution represents the voltage distribution over the winding in each moment of the LI-time (50μs). The results verification by comparison against measurements is presented in detail

Taste-immune associative learning amplifies immunopharmacological effects and attenuates disease progression in a rat glioblastoma model

Mechanistic target of rapamycin (mTOR)-signaling is one key driver of glioblastoma (GBM), facilitating tumor growth by promoting the shift to an anti-inflammatory, pro-cancerogenic microenvironment. Even though mTOR inhibitors such as rapamycin (RAPA) have been shown to interfere with GBM disease progression, frequently chaperoned toxic drug side effects urge the need for developing alternative or supportive treatment strategies. Importantly, previous work document that taste-immune associative learning with RAPA may be utilized to induce learned pharmacological placebo responses in the immune system. Against this background, the current study aimed at investigating the potential efficacy of a taste-immune associative learning protocol with RAPA in a syngeneic GBM rat model. Following repeated pairings of a novel gustatory stimulus with injections of RAPA, learned immune-pharmacological effects could be retrieved in GBM-bearing animals when re-exposed to the gustatory stimulus together with administering 10 % amount of the initial drug dose (0.5 mg/kg). These inhibitory effects on tumor growth were accompanied by an up-regulation of central and peripheral pro-inflammatory markers, suggesting that taste-immune associative learning with RAPA promoted the development of a pro-inflammatory anti-tumor microenvironment that attenuated GBM tumor growth to an almost identical outcome as obtained after 100 % (5 mg/kg) RAPA treatment. Together, our results confirm the applicability of taste-immune associative learning with RAPA in animal disease models where mTOR overactivation is one key driver. This proof-of-concept study may also be taken as a role model for implementing learning protocols as alternative or supportive treatment strategy in clinical settings, allowing the reduction of required drug doses and side effects without losing treatment efficacy

Differential requirement of kindlin-3 for T cell progenitor homing to the non-vascularized and vascularized thymus

The role of integrin-mediated adhesion during T cell progenitor homing to and differentiation within the thymus is ill-defined, mainly due to functional overlap. To circumvent compensation, we disrupted the hematopoietic integrin regulator kindlin-3 in mice and found a progressive thymus atrophy that is primarily caused by an impaired homing capacity of T cell progenitors to the vascularized thymus. Notably, the low shear flow conditions in the vascular system at midgestation allow kindlin-3-deficient fetal liver-derived T cell progenitors to extravasate via pharyngeal vessels and colonize the avascular thymus primordium. Once in the thymus, kindlin-3 promotes intrathymic T cell proliferation by facilitating the integrin-dependent crosstalk with thymic antigen presenting cells, while intrathymic T cell migration, maturation into single positive CD4 and CD8 T cells and release into the circulation proceed without kindlin-3. Thus, kindlin-3 is dispensable for integrin-mediated T cell progenitor adhesion and signalling at low and indispensable at high shear forces

Comparison of the respiratory bacterial microbiome in cats with feline asthma and chronic bronchitis

ObjectivesWhile feline chronic bronchitis (CB) is known as neutrophilic bronchial inflammation (NI), feline asthma (FA) is defined as an eosinophilic airway inflammation (EI). Feline chronic bronchial disease refers to both syndromes, with similar clinical presentations and applied treatment strategies. Recent studies described alterations of the microbiota composition in cats with FA, but little is known about the comparison of the lung microbiota between different types of feline bronchial disease. The study aimed to describe the bacterial microbiota of the lower respiratory tracts of cats with FA and CB and to identify potential differences.MethodsTwenty-two client-owned cats with FA (n = 15) or CB (n = 7) confirmed via bronchoalveolar-lavage (BALF)-cytology were included. Next-generation sequencing analysis of 16S rRNA genes was performed on bacterial DNA derived from BALF samples. QIIME was used to compare microbial composition and diversity between groups.ResultsEvenness and alpha-diversity-indices did not significantly differ between cats with FA and CB (Shannon p = 0.084, Chao 1 p = 0.698, observed ASVs p = 0.944). Based on a PERMANOVA analysis, no significant differences were observed in microbial composition between animals of both groups (Bray-Curtis metric, R-value 0.086, p = 0.785; unweighted UniFrac metric, R-value −0.089, p = 0.799; weighted Unifrac metric, R-value −0.072, p = 0.823). Regarding taxonomic composition, significant differences were detected for Actinobacteria on the phylum level (p = 0.026), Mycoplasma spp. (p = 0.048), and Acinetobacteria (p = 0.049) on the genus level between cats with FA and CB, with generally strong interindividual differences seen. There was a significant difference in the duration of clinical signs before diagnosis in animals dominated by Bacteriodetes (median 12 months, range 2–58 months) compared to animals dominated by Proteobacteria (median 1 month, range 1 day to 18 months; p = 0.003).Conclusions and relevanceLung microbiota composition is very similar in cat populations with spontaneous FA and CB besides small differences in some bacterial groups. However, with disease progression, the lung microbiome of cats with both diseases appears to shift away from dominantly Proteobacteria to a pattern more dominated by Bacteriodetes. A substantial proportion of cats tested positive for Mycoplasma spp. via sequencing, while none of them tested positive using classical PCR