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We present a model for the autonomous and simultaneous learning of active binocular and motion vision. The model is based on the Active Efficient Coding (AEC) framework, a recent generalization of classic efficient coding theories to active perception. The model learns how to efficiently encode the incoming visual signals generated by an object moving in 3-D through sparse coding. Simultaneously, it learns how to produce eye movements that further improve the efficiency of the sensory coding. This learning is driven by an intrinsic motivation to maximize the system's coding efficiency. We test our approach on the humanoid robot iCub using simulations. The model demonstrates self-calibration of accurate object fixation and tracking of moving objects. Our results show that the model keeps improving until it hits physical constraints such as camera or motor resolution, or limits on its internal coding capacity. Furthermore, we show that the emerging sensory tuning properties are in line with results on disparity, motion, and motion-in-depth tuning in the visual cortex of mammals. The model suggests that vergence and tracking eye movements can be viewed as fundamentally having the same objective of maximizing the coding efficiency of the visual system and that they can be learned and calibrated jointly through AEC.
Small-scale phenotypic differentiation along complex stream gradients in a non-native amphipod
(2019)
Background: Selective landscapes in rivers are made up by an array of selective forces that vary from source to downstream regions or between seasons, and local/temporal variation in fitness maxima can result in gradual spatio-temporal variation of phenotypic traits. This study aimed at establishing freshwater amphipods as future model organisms to study adaptive phenotypic diversification (evolutionary divergence and/or adaptive plasticity) along stream gradients.
Methods: We collected Gammarus roeselii from 16 sampling sites in the Rhine catchment during two consecutive seasons (summer and winter). Altogether, we dissected n = 1648 individuals and quantified key parameters related to morphological and life-history diversification, including naturally selected (e.g., gill surface areas) as well as primarily sexually selected traits (e.g., male antennae). Acknowledging the complexity of selective regimes in streams and the interrelated nature of selection factors, we assessed several abiotic (e.g., temperature, flow velocity) and biotic ecological parameters (e.g., conspecific densities, sex ratios) and condensed them into four principal components (PCs).
Results: Generalized least squares models revealed pronounced phenotypic differentiation in most of the traits investigated herein, and components of the stream gradient (PCs) explained parts of the observed differences. Depending on the trait under investigation, phenotypic differentiation could be ascribed to variation in abiotic conditions, anthropogenic disturbance (influx of thermally polluted water), or population parameters. For example, female fecundity showed altitudinal variation and decreased with increasing conspecific densities, while sexual dimorphism in the length of male antennae—used for mate finding and assessment—increased with increasing population densities and towards female-biased sex ratios.
Conclusions: We provide a comprehensive protocol for comparative analyses of intraspecific variation in life history traits in amphipods. Whether the observed phenotypic differentiation over small geographical distances reflects evolutionary divergence or plasticity (or both) remains to be investigated in future studies. Independent of the mechanisms involved, variation in several traits is likely to have consequences for ecosystem functions. For example, leaf-shredding in G. roeselii strongly depends on body size, which varied in dependence of several ecological parameters.
Chirality is omnipresent in living nature. On the single molecule level, the response of a chiral species to a chiral probe depends on their respective handedness. A prominent example is the difference in the interaction of a chiral molecule with left or right circularly polarized light. In the present study, we show by Coulomb explosion imaging that circularly polarized light can also induce a chiral fragmentation of a planar and thus achiral molecule. The observed enantiomer strongly depends on the orientation of the molecule with respect to the light propagation direction and the helicity of the ionizing light. This finding might trigger new approaches to improve laser-driven enantioselective chemical synthesis.
Adhesion molecules of the integrin beta1 family are thought to be involved in the malignant progression renal cell carcinoma (RCC). Still, it is not clear how they contribute to this process. Since the hematogenous phase of tumour dissemination is the rate-limiting step in the metastatic process, we explored beta1 integrin alterations on several RCC cell lines (A498, Caki1, KTC26) before and after contacting vascular endothelium in a tumour-endothelium (HUVEC) co-culture assay. Notably, alpha2, alpha3 and alpha5 integrins became down-regulated immediately after the tumour cells attached to HUVEC, followed by re-expression shortly thereafter. Integrin down-regulation on RCC cells was caused by direct contact with endothelial cells, since the isolated endothelial membrane fragments but not the cell culture supernatant contributed to the observed effects. Integrin loss was accompanied by a reduced focal adhesion kinase (FAK) expression, FAK activity and diminished binding of tumour cells to matrix proteins. Furthermore, intracellular signalling proteins RCC cells were altered in the presence of HUVEC membrane fragments, in particular 14-3-3 epsilon, ERK2, PKCdelta, PKCepsilon and RACK1, which are involved in regulating tumour cell motility. We, therefore, speculate that contact of RCC cells with the vascular endothelium converts integrin-dependent adhesion to integrin-independent cell movement. The process of dynamic integrin regulation may be an important part in tumour cell migration strategy, switching the cells from being adhesive to becoming motile and invasive.
Histone deacetylase (HDAC) inhibitors represent a promising class of antineoplastic agents which affect tumour growth, differentiation and invasion. The effects of the HDAC inhibitor valproic acid (VPA) were tested in vitro and in vivo on pre-clinical renal cell carcinoma (RCC) models. Caki-1, KTC-26 or A498 cells were treated with various concentrations of VPA during in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and to evaluate cell cycle manipulation. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. The anti-tumoural potential of VPA combined with low-dosed interferon-α (IFN-α) was also investigated. VPA significantly and dose-dependently up-regulated histones H3 and H4 acetylation and caused growth arrest in RCC cells. VPA altered cell cycle regulating proteins, in particular CDK2, cyclin B, cyclin D3, p21 and Rb. In vivo, VPA significantly inhibited the growth of Caki-1 in subcutaneous xenografts, accompanied by a strong accumulation of p21 and bax in tissue specimens of VPA-treated animals. VPA–IFN-α combination markedly enhanced the effects of VPA monotherapy on RCC proliferation in vitro, but did not further enhance the anti-tumoural potential of VPA in vivo. VPA was found to have profound effects on RCC cell growth, lending support to the initiation of clinical testing of VPA for treating advanced RCC.
New histone deacetylase inhibitors as potential therapeutic tools for advanced prostate carcinoma
(2008)
The anti-epileptic drug valproic acid is also under trial as an anti-cancer agent due to its histone deacetylase (HDAC) inhibitory properties. However, the effects of valproic acid (VPA) are limited and concentrations required for exerting anti-neoplastic effects in vitro may not be reached in tumour patients. In this study, we tested in vitro and in vivo effects of two VPA-derivatives (ACS2, ACS33) on pre-clinical prostate cancer models. PC3 and DU-145 prostate tumour cell lines were treated with various concentrations of ACS2 or ACS33 to perform in vitro cell proliferation 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and to evaluate tumour cell adhesion to endothelial cell monolayers. Analysis of acetylated histones H3 and H4 protein expression was performed by western blotting. In vivo tumour growth was conducted in subcutaneous xenograft mouse models. Tumour sections were assessed by immunohistochemistry for histone H3 acetylation and proliferation. ACS2 and ACS33 significantly up-regulated histone H3 and H4 acetylation in prostate cancer cell lines. In micromolar concentrations both compounds exerted growth arrest in PC3 and DU-145 cells and prevented tumour cell attachment to endothelium. In vivo, ACS33 inhibited the growth of PC3 in subcutaneous xenografts. Immunohistochemistry and western blotting confirmed increased histone H3 acetylation and reduced proliferation. ACS2 and ACS33 represent novel VPA derivatives with superior anti-tumoural activities, compared to the mother compound. This investigation lends support to the clinical testing of ACS2 or ACS33 for the treatment of prostate cancer.
Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.
Chatbots become human(like): the influence of gender on cooperative interactions with chatbots
(2019)
CURRENT TECHNOLOGICAL ADVANCEMENTS OF CONVERSATIONAL AGENTS (CAs) PROMISE NEW POTENTIALS FOR HUMAN-COMPUTER COLLABORATIONS. YET, BOTH PRACTITIONERS AND RESEARCHERS FACE CHALLENGES IN DESIGNING THESE INFORMATION SYSTEMS, SUCH THAT CAs NOT ONLY INCREASE IN INTELLIGENCE BUT ALSO IN EFFECTIVENESS. THROUGH OUR RESEARCH ENDEAVOUR, WE PROVIDE NEW AND COUNTERINTUITIVE INSIGHTS THAT ARE CRUCIAL FOR THE EFFECTIVE DESIGN OF COOPERATIVE CAs.
Humanized mouse models have become increasingly valuable tools to study human hematopoiesis and infectious diseases. However, human T cell differentiation remains inefficient. We generated mice expressing human interleukin (IL-7), a critical growth and survival factor for T cells, under the control of murine IL-7 regulatory elements. After transfer of human cord blood-derived hematopoietic stem and progenitor cells, transgenic mice on the NSGW41 background, termed NSGW41hIL7, showed elevated and prolonged human cellularity in the thymus while maintaining physiological ratios of thymocyte subsets. As a consequence, numbers of functional human T cells in the periphery were increased without evidence for pathological lymphoproliferation or aberrant expansion of effector or memory-like T cells. We conclude that the novel NSGW41hIL7 strain represents an optimized mouse model for humanization to better understand human T cell differentiation in vivo and to generate a human immune system with a better approximation of human lymphocyte ratios.
This study describes the chemical composition and in vitro toxicity of the organic fraction of fine particulate matter (PM2.5) at an urban background site, which receives emissions either from Frankfurt international airport or the city centre, respectively. We analysed the chemical composition of filter extracts (PM2.5) using ultrahigh-performance liquid chromatography coupled to a high-resolution mass spectrometer, followed by a non-target analysis. In parallel, we applied the bulk of the filter extracts to a Microtox and acetylcholinesterase-inhibition assay for in vitro toxicity testing. We find that both the chemical composition and toxicity depend on the prevailing wind directions, and the airport operating condition, respectively. The occurrence of the airport marker compounds tricresyl phosphate and pentaerythritol esters depends on the time of the day, reflecting the night flight ban as well as an airport strike event during November 2019. We compared the organic aerosol composition and toxicity from the airport wind-sector against the city centre wind-sector. We find that urban background aerosol shows a higher baseline toxicity and acetylcholinesterase inhibition compared to rural PM2.5 that is advected over the airport. Our results indicate that the concentration and individual composition of PM2.5 influence the toxicity. Suspected drivers of the acetylcholinesterase inhibition are i.e. organophosphorus esters like triphenyl phosphate and cresyldiphenyl phosphate, and the non-ionic surfactant 4-tert-octylphenol ethoxylate. However, further research is necessary to unambiguously identify harmful organic air pollutants and their sources and quantify concentration levels at which adverse effects in humans and the environment can occur.