Software to convert terrestrial LiDAR scans of natural environments into photorealistic meshes

The introduction of 3D scanning has strongly influenced environmental sciences. If the resulting point clouds can be transformed into polygon meshes, a vast range of visualisation and analysis tools can be applied. But extracting accurate meshes from large point clouds gathered in natural environments is not trivial, requiring a suite of customisable processing steps. We present Habitat3D, an open source software tool to generate photorealistic meshes from registered point clouds of natural outdoor scenes. We demonstrate its capability by extracting meshes of different environments: 8,800 m2 grassland featuring several Eucalyptus trees (combining 9 scans and 41,989,885 data points); 1,018 m2 desert densely covered by vegetation (combining 56 scans and 192,223,621 data points); a well-structured garden; and a rough, volcanic surface. The resultant reconstructions accurately preserve all spatial features with millimetre accuracy whilst reducing the memory load by up to 98.5%. This enables rapid visualisation of the environments using off-the-shelf game engines and graphics hardware

Molecularly Characterised Xenograft Tumour Mouse Models: Valuable Tools for Evaluation of New Therapeutic Strategies for Secondary Liver Cancers

To develop and evaluate new therapeutic strategies for the treatment of human cancers, well-characterised preclinical model systems are a prerequisite. To this aim, we have established xenotransplantation mouse models and corresponding cell cultures from surgically obtained secondary human liver tumours. Established xenograft tumours were patho- and immunohistologically characterised, and expression levels of cancer-relevant genes were quantified in paired original and xenograft tumours and the derivative cell cultures applying RT-PCR-based array technology. Most of the characteristic morphological and immunohistochemical features of the original tumours were shown to be maintained. No differences were found concerning expression of genes involved in cell cycle regulation and oncogenesis. Interestingly, cytokine and matrix metalloproteinase encoding genes appeared to be expressed differentially. Thus, the established models are closely reflecting pathohistological and molecular characteristics of the selected human tumours and may therefore provide useful tools for preclinical analyses of new antitumour strategies in vivo

Electroluminescence from chirality-sorted (9,7)-semiconducting carbon nanotube devices

We have measured the electroluminescence and photoluminescence of (9,7) semiconducting carbon nanotube devices and demonstrate that the electroluminescence wavelength is determined by the nanotube's chiral index (n,m). The devices were fabricated on Si3N4 membranes by dielectrophoretic assembly of tubes from monochiral dispersion. Electrically driven (9,7) devices exhibit a single Lorentzian shaped emission peak at 825 nm in the visible part of the spectrum. The emission could be assigned to the excitonic E22 interband transition by comparison of the electroluminescence spectra with corresponding photoluminescence excitation maps. We show a linear dependence of the EL peak width on the electrical current, and provide evidence for the inertness of Si3N4 surfaces with respect to the nanotubes optical properties.Comment: 6 pages, 3 figures, submitted to Optics Expres

Chirurgische Therapie des Adenokarzinoms des ösophagogastralen Übergangs Typ II : Vergleich zwischen transhiatal erweiterter Gastrektomie und thorakoabdomineller Ösophagektomie

Hintergrund Trotz steigender Inzidenz ist die optimale chirurgische Versorgung des Adenokarzinoms des ösophagogastralen Übergangs (AEG) Typ II weiterhin Gegenstand aktueller Forschung. Ziel dieser Untersuchung ist es, Überlebens- und Rezidivraten von Patienten zu vergleichen, die sich entweder einer transhiatal erweiterten Gastrektomie (TEG) oder einer thorakoabdominellen Ösophagektomie (TAE) unterzogen. Material und Methoden Es handelt es sich um eine retrospektive populationsbasierte Kohortenstudie (n = 272) auf der Basis von Krebsregisterdaten. Berücksichtigt wurden alle Patienten, die zwischen 2002 und 2020 an einem AEG Typ II erkrankten. Während 63 Patienten mittels TAE operiert wurden, gehören der Gruppe der TEG 209 Patienten an. Um das Gesamtüberleben, Rezidivraten und rezidivfreies Überleben zu untersuchen, wurden die Kaplan-Meier-Methode sowie uni- und multivariable Cox-Regressionen angewendet. Ergebnisse Zwischen beiden Operationsgruppen gab es bezüglich des Gesamtüberlebens keinen signifikanten Unterschied (p = 0,333). Allerdings ließ die Richtung der HR im Zeitraum von 2016 bis 2020 eine mögliche Tendenz in Richtung der TAE erkennen (p = 0,058). Im Gegensatz dazu ergab der Kaplan-Meier-Schätzer ein signifikant höheres Risiko, nach einer TAE an einem Rezidiv zu erkranken (p = 0,049). Dies konnte nicht im Zeitraum 2016 bis 2020, der mehr als die Hälfte der TAE-Patienten umfasst, beobachtet werden (p = 0,993). Hinsichtlich des rezidivfreien Überlebens wurden keine signifikanten Unterschiede detektiert (p = 0,772). Diskussion Die Ergebnisse dieser verhältnismäßig kleinen Kohorte decken sich mit den meisten Studien, die hinsichtlich des Gesamtüberlebens entweder keine Unterschiede oder eine Tendenz in Richtung der TAE fanden. Weitere Arbeiten kamen ebenfalls zu dem Ergebnis, dass es keine signifikanten Unterschiede zwischen den beiden Operationsgruppen bezüglich des rezidivfreien Überlebens gibt. Zusammenfassend lässt sich festhalten, dass es keine signifikanten Unterschiede zwischen TEG und TAE in der Therapie des AEG Typ II gibt

Identification of Predictive Markers for Response to Neoadjuvant Chemoradiation in Rectal Carcinomas by Proteomic Isotope Coded Protein Label (ICPL) Analysis

Neoadjuvant chemoradiation (nCRT) is an established procedure in stage union internationale contre le cancer (UICC) II/III rectal carcinomas. Around 53% of the tumours present with good tumor regression after nCRT, and 8%-15% are complete responders. Reliable selection markers would allow the identification of poor or non-responders prior to therapy. Tumor biopsies were harvested from 20 patients with rectal carcinomas, and stored in liquid nitrogen prior to therapy after obtaining patients’ informed consent (Erlangen-No.3784). Patients received standardized nCRT with 5-Fluoruracil (nCRT I) or 5-Fluoruracil ± Oxaliplatin (nCRT II) according to the CAO/ARO/AIO-04 protocol. After surgery, regression grading (Dworak) of the tumors was performed during histopathological examination of the specimens. Tumors were classified as poor (Dworak 1 + 2) or good (Dworak 3 + 4) responders. Laser capture microdissection (LCM) for tumor enrichment was performed on preoperative biopsies. Differences in expressed proteins between poor and good responders to nCRT I and II were identified by proteomic analysis (Isotope Coded Protein Label, ICPL™) and selected markers were validated by immunohistochemistry. Tumors of 10 patients were classified as histopathologically poor (Dworak 1 or 2) and the other 10 tumor samples as histopathologically good (Dworak 3 or 4) responders to nCRT after surgery. Sufficient material in good quality was harvested for ICPL analysis by LCM from all biopsies. We identified 140 differentially regulated proteins regarding the selection criteria and the response to nCRT. Fourteen of these proteins were synchronously up-regulated at least 1.5-fold after nCRT I or nCRT II (e.g., FLNB, TKT, PKM2, SERINB1, IGHG2). Thirty-five proteins showed a complete reciprocal regulation (up or down) after nCRT I or nCRT II and the rest was regulated either according to nCRT I or II. The protein expression of regulated proteins such as PLEC1, TKT, HADHA and TAGLN was validated successfully by immunohistochemistry. ICPL is a valid method to identify differentially expressed proteins in rectal carcinoma tissue between poor vs. good responders to nCRT. The identified protein markers may act as selection criteria for nCRT in the future, but our preliminary findings must be reproduced and validated in a prospective cohort

Inhibition of integrin αvβ6 sparks T-cell antitumor response and enhances immune checkpoint blockade therapy in colorectal cancer

BACKGROUND Integrin αvβ6 is a heterodimeric cell surface protein whose cellular expression is determined by the availability of the integrin β6 subunit (ITGB6). It is expressed at very low levels in most organs during tissue homeostasis but shows highly upregulated expression during the process of tumorigenesis in many cancers of epithelial origin. Notably, enhanced expression of integrin αvβ6 is associated with aggressive disease and poor prognosis in numerous carcinoma entities. Integrin αvβ6 is one of the major physiological activators of transforming growth factor-β (TGF-β), which has been shown to inhibit the antitumor T-cell response and cause resistance to immunotherapy in mouse models of colorectal and mammary cancer. In this study, we investigated the effect of ITGB6 expression and antibody-mediated integrin αvβ6 inhibition on the tumor immune response in colorectal cancer. METHODS Using orthotopic and heterotopic tumor cell injection, we assessed the effect of ITGB6 on tumor growth and tumor immune response in wild type mice, mice with defective TGF-β signaling, and mice treated with anti-integrin αvβ6 antibodies. To examine the effect of ITGB6 in human colorectal cancer, we analyzed RNAseq data from the colon adenocarcinoma dataset of The Cancer Genome Atlas (TCGA-COAD). RESULTS We demonstrate that expression of ITGB6 is an immune evasion strategy in colorectal cancer, causing inhibition of the antitumor immune response and resistance to immune checkpoint blockade therapy by activating latent TGF-β. Antibody-mediated inhibition of integrin αvβ6 sparked a potent cytotoxic T-cell response and overcame resistance to programmed cell death protein 1 (PD-1) blockade therapy in ITGB6 expressing tumors, provoking a drastic increase in anti-PD-1 treatment efficacy. Further, we show that the majority of tumors in patients with colorectal cancer express sufficient ITGB6 to provoke inhibition of the cytotoxic T-cell response, indicating that most patients could benefit from integrin αvβ6 blockade therapy. CONCLUSIONS These findings propose inhibition of integrin αvβ6 as a promising new therapy for colorectal cancer, which blocks tumor-promoting TGF-β activation, prevents tumor exclusion of cytotoxic T-cells and enhances the efficacy of immune checkpoint blockade therapy

KETOS: Clinical decision support and machine learning as a service – A training and deployment platform based on Docker, OMOP-CDM, and FHIR Web Services

Background and objective To take full advantage of decision support, machine learning, and patient-level prediction models, it is important that models are not only created, but also deployed in a clinical setting. The KETOS platform demonstrated in this work implements a tool for researchers allowing them to perform statistical analyses and deploy resulting models in a secure environment. Methods The proposed system uses Docker virtualization to provide researchers with reproducible data analysis and development environments, accessible via Jupyter Notebook, to perform statistical analysis and develop, train and deploy models based on standardized input data. The platform is built in a modular fashion and interfaces with web services using the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) standard to access patient data. In our prototypical implementation we use an OMOP common data model (OMOP-CDM) database. The architecture supports the entire research lifecycle from creating a data analysis environment, retrieving data, and training to final deployment in a hospital setting. Results We evaluated the platform by establishing and deploying an analysis and end user application for hemoglobin reference intervals within the University Hospital Erlangen. To demonstrate the potential of the system to deploy arbitrary models, we loaded a colorectal cancer dataset into an OMOP database and built machine learning models to predict patient outcomes and made them available via a web service. We demonstrated both the integration with FHIR as well as an example end user application. Finally, we integrated the platform with the open source DataSHIELD architecture to allow for distributed privacy preserving data analysis and training across networks of hospitals. Conclusion The KETOS platform takes a novel approach to data analysis, training and deploying decision support models in a hospital or healthcare setting. It does so in a secure and privacy-preserving manner, combining the flexibility of Docker virtualization with the advantages of standardized vocabularies, a widely applied database schema (OMOP-CDM), and a standardized way to exchange medical data (FHIR)

PU.1 controls fibroblast polarization and tissue fibrosis

Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs

Ant homing ability is not diminished when traveling backwards

Ants are known to be capable of homing to their nest after displacement to a novel location. This is widely assumed to involve some form of retinotopic matching between their current view and previously experienced views. One simple algorithm proposed to explain this behavior is continuous retinotopic alignment, in which the ant constantly adjusts its heading by rotating to minimize the pixel-wise difference of its current view from all views stored while facing the nest. However, ants with large prey items will often drag them home while facing backwards. We tested whether displaced ants (Myrmecia croslandi) dragging prey could still home despite experiencing an inverted view of their surroundings under these conditions. Ants moving backwards with food took similarly direct paths to the nest as ants moving forward without food, demonstrating that continuous retinotopic alignment is not a critical component of homing. It is possible that ants use initial or intermittent retinotopic alignment, coupled with some other direction stabilizing cue that they can utilize when moving backward. However, though most ants dragging prey would occasionally look toward the nest, we observed that their heading direction was not noticeably improved afterwards. We assume ants must use comparison of current and stored images for corrections of their path, but suggest they are either able to chose the appropriate visual memory for comparison using an additional mechanism; or can make such comparisons without retinotopic alignment