Modeling and solving line planning with integrated mode choice

We present a mixed-integer linear program (MILP) for line planning with integrated mode and route choice. In contrast to existing approaches, the mode and route decisions are modeled according to the passengers' preferences while commercial solvers can be applied to solve the corresponding MILP. The model aims at finding line plans that maximize the profit for the public transport operator while estimating the corresponding passenger demand with choice models. Both components of profit, revenue and cost, are influenced by the line plan. Hence, the resulting line plans are not only profitable for operators but also attractive to passengers. By suitable preprocessing of the passengers' utilities, we are able to apply any choice model for mode choices using linear constraints. We provide and test means to improve the computational performance. In experiments on the Intercity network of the Randstad, a metropolitan area in the Netherlands, we show the benefits of our model compared to a standard line planning model with fixed passenger demand. Furthermore, we demonstrate with the help of our model the possibilities and limitations for operators when reacting to changes in demand in an optimal way. The results suggest that operators should regularly update their line plan in response to changes in travel demand and estimate the passenger demand during optimization

A good or a bad timetable: Do different evaluation functions agree?

Abstract We compare different evaluation functions that are all designed to mea- sure the quality of a timetable from passengers’ perspective. Already in small examples fundamentally different timetables can be preferred by evaluation functions that seem to be similar. To investigate this effect in practice, we design a set of evaluation functions as representatives for a wide range of commonly used evaluation functions in optimization models, evaluation applications, or choice models. These functions are compared by analyzing their evaluation values of multiple timetables in three case studies. To investigate to what extent these evaluation functions agree on a good or a bad timetable, we apply cluster analysis as well as a novel methodology to quantify the similarity of pairs of evaluation functions based on the values they yield on different timetables. We empirically show that the choice of the evaluation function can have a significant impact on the assessed quality of timetables, and thus also on which timetable is considered optimal, even though all evaluation functions are meant to evaluate the same - the quality of a timetable from passengers’ perspective. Due to the structure of the designed evaluation functions, it is further possible to identify which components of the func- tions influence the results of an evaluation and under which conditions they this is most pronounced. This can be very beneficial when designing timetable evaluation functions for passengers

Molecular insights into antibiotic resistance - how a binding protein traps albicidin

The worldwide emergence of antibiotic resistance poses a serious threat to human health. A molecular understanding of resistance strategies employed by bacteria is obligatory to generate less-susceptible antibiotics. Albicidin is a highly potent antibacterial compound synthesized by the plant-pathogenic bacterium Xanthomonas albilineans. The drug-binding protein AlbA confers albicidin resistance to Klebsiella oxytoca. Here we show that AlbA binds albicidin with low nanomolar affinity resulting in full inhibition of its antibacterial activity. We report on the crystal structure of the drug-binding domain of AlbA (AlbAS) in complex with albicidin. Both α-helical repeat domains of AlbAS are required to cooperatively clamp albicidin, which is unusual for drug-binding proteins of the MerR family. Structure-guided NMR binding studies employing synthetic albicidin derivatives give valuable information about ligand promiscuity of AlbAS. Our findings thus expand the general understanding of antibiotic resistance mechanisms and support current drug-design efforts directed at more effective albicidin analogs

The unexpected resurgence of Weyl geometry in late 20-th century physics

Weyl's original scale geometry of 1918 ("purely infinitesimal geometry") was withdrawn by its author from physical theorizing in the early 1920s. It had a comeback in the last third of the 20th century in different contexts: scalar tensor theories of gravity, foundations of gravity, foundations of quantum mechanics, elementary particle physics, and cosmology. It seems that Weyl geometry continues to offer an open research potential for the foundations of physics even after the turn to the new millennium.Comment: Completely rewritten conference paper 'Beyond Einstein', Mainz Sep 2008. Preprint ELHC (Epistemology of the LHC) 2017-02, 92 pages, 1 figur

Strain-dependent host transcriptional responses to toxoplasma infection are largely conserved in mammalian and avian hosts

Toxoplasma gondii has a remarkable ability to infect an enormous variety of mammalian and avian species. Given this, it is surprising that three strains (Types I/II/III) account for the majority of isolates from Europe/North America. The selective pressures that have driven the emergence of these particular strains, however, remain enigmatic. We hypothesized that strain selection might be partially driven by adaptation of strains for mammalian versus avian hosts. To test this, we examine in vitro, strain-dependent host responses in fibroblasts of a representative avian host, the chicken (Gallus gallus). Using gene expression profiling of infected chicken embryonic fibroblasts and pathway analysis to assess host response, we show here that chicken cells respond with distinct transcriptional profiles upon infection with Type II versus III strains that are reminiscent of profiles observed in mammalian cells. To identify the parasite drivers of these differences, chicken fibroblasts were infected with individual F1 progeny of a Type II x III cross and host gene expression was assessed for each by microarray. QTL mapping of transcriptional differences suggested, and deletion strains confirmed, that, as in mammalian cells, the polymorphic rhoptry kinase ROP16 is the major driver of strain-specific responses. We originally hypothesized that comparing avian versus mammalian host response might reveal an inversion in parasite strain-dependent phenotypes; specifically, for polymorphic effectors like ROP16, we hypothesized that the allele with most activity in mammalian cells might be less active in avian cells. Instead, we found that activity of ROP16 alleles appears to be conserved across host species; moreover, additional parasite loci that were previously mapped for strain-specific effects on mammalian response showed similar strain-specific effects in chicken cells. These results indicate that if different hosts select for different parasite genotypes, the selection operates downstream of the signaling occurring during the beginning of the host's immune response. © 2011 Ong et al

On the Dialectics of Charisma in Marina Abramović’s The Artist is Present

While ‘charisma’ can be found in dramatic and theatrical parlance, the term enjoys only minimal critical attention in theatre and performance studies, with scholarly work on presence and actor training methods taking the lead in defining charisma’s supposed ‘undefinable’ quality. Within this context, the article examines the appearance of the term ‘charismatic space’ in relation to Marina Abramovic’s retrospective The Artist is Present at New York’s Museum of Modern Art in 2010. Here Abramovic uses this term to describe the shared space in which performer and spectator connect bodily, psychically, and spiritually through a shared sense of presence and energy in the moment of performance. Yet this is a space arguably constituted through a number of dialectical tensions and contradictions which, in dialogue with existing theatre scholarship on charisma, can be further understood by drawing on insights into charismatic leaders and charismatic authority in leadership studies. By examining the performance and its documentary traces in terms of dialectics we consider the political and ethical implications for how we think about power relations between artist/spectator in a neoliberal, market-driven art context. Here an alternative approach to conceiving of and facilitating a charismatic space is proposed which instead foregrounds what Bracha L. Ettinger calls a ‘matrixial encounter-event’: A relation of coexistence and compassion rather than dominance of self over other; performer over spectator; leader over follower. By illustrating the dialectical tensions in The Artist is Present, we consider the potential of the charismatic space not as generated through the seductive power or charm of an individual whose authority is tied to his/her ‘presence’, but as something co-produced within an ethical and relational space of trans-subjectivity

Factors associated with worse lung function in cystic fibrosis patients with persistent staphylococcus aureus

Background Staphylococcus aureus is an important pathogen in cystic fibrosis (CF). However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures. Our main hypothesis was that patients with high S. aureus density in their respiratory specimens would more likely experience worsening of their lung disease than patients with low bacterial loads. Methods Therefore, we conducted an observational prospective longitudinal multi-center study and assessed the association between lung function and S. aureus bacterial density in respiratory samples, co-infection with other CF-pathogens, nasal S. aureus carriage, clinical status, antibiotic therapy, IL-6- and IgG-levels against S. aureus virulence factors. Results 195 patients from 17 centers were followed; each patient had an average of 7 visits. Data were analyzed using descriptive statistics and generalized linear mixed models. Our main hypothesis was only supported for patients providing throat specimens indicating that patients with higher density experienced a steeper lung function decline (p<0.001). Patients with exacerbations (n = 60), S. aureus small-colony variants (SCVs, n = 84) and co-infection with Stenotrophomonas maltophilia (n = 44) had worse lung function (p = 0.0068; p = 0.0011; p = 0.0103). Patients with SCVs were older (p = 0.0066) and more often treated with trimethoprim/sulfamethoxazole (p = 0.0078). IL-6 levels positively correlated with decreased lung function (p<0.001), S. aureus density in sputa (p = 0.0016), SCVs (p = 0.0209), exacerbations (p = 0.0041) and co-infections with S. maltophilia (p = 0.0195) or A. fumigatus (p = 0.0496). Conclusions In CF-patients with chronic S. aureus cultures, independent risk factors for worse lung function are high bacterial density in throat cultures, exacerbations, elevated IL-6 levels, presence of S. aureus SCVs and co-infection with S. maltophilia

Factors Associated with Bovine Neonatal Pancytopenia (BNP) in Calves: A Case-Control Study

Bovine neonatal pancytopenia (BNP; previously known as idiopathic haemorrhagic diathesis and commonly known as bleeding calf syndrome) is a novel haemorrhagic disease of young calves which has emerged in a number of European countries during recent years. Data were retrospectively collected during June to November 2010 for 56 case calves diagnosed with BNP between 17 March and 7 June of the same year. These were compared with 58 control calves randomly recruited from herds with no history of BNP. Multivariable logistic regression analysis showed that increased odds of a calf being a BNP case were associated with its dam having received PregSure® BVD (Pfizer Animal Health) vaccination prior to the birth of the calf (odds ratio (OR) 40.78, p<0.001) and its herd of origin being located in Scotland (OR 9.71, p = 0.006). Decreased odds of a calf being a BNP case were associated with the calf having been kept outside (OR 0.11, p = 0.006). The longer that a cattle herd had been established on the farm was also associated with decreased odds of a calf in that herd being a BNP case (OR 0.97, p = 0.011)

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin