Metaphysische Maschinen

Heiko Schmid beschäftigt sich mit so unterschiedlichen und gleichzeitig faszinierenden Phänomenen wie der populären Astronomie, der Künstlerbewegung der Futuristen, dem Science-Fiction-Genre, den Entstehungszusammenhängen der Raketentechnologien und dem Theorem der vierten Dimension. All diese vielfältigen Themenfelder verbindet er hierbei mit einer Annäherung an das Konzept der Maschine. Das zentrale Anliegen der Studie ist es, den Maschinenbegriff kultur- und kunsthistorisch in einen komplexen Rahmen technoimaginativer Entwicklungen einzubetten

A Dynamical Model of Binding in Visual Cortex During Incremental Grouping and Search

Binding of visual information is crucial for several perceptual tasks. To incrementally group an object, elements in a space-feature neighborhood need to be bound together starting from an attended location (Roelfsema, TICS, 2005). To perform visual search, candidate locations and cued features must be evaluated conjunctively to retrieve a target (Treisman&Gormican, Psychol Rev, 1988). Despite different requirements on binding, both tasks are solved by the same neural substrate. In a model of perceptual decision-making, we give a mechanistic explanation for how this can be achieved. The architecture consists of a visual cortex module and a higher-order thalamic module. While the cortical module extracts stimulus features across a hierarchy of spatial scales, the thalamic module provides a purely spatial relevance map. Both modules interact bidirectionally to enter locations of task-relevance into thalamus, while allowing integration of context with local features within cortical maps. This integration realizes the model\u27s binding mechanism. It is implemented by pyramidal neurons with dynamical basal and apical compartments performing coincidence detection (Larkum, TINS, 2013). The basal compartment is driven by bottom-up feature information and produces the neuron\u27s output, the apical compartment computes top-down contextual information akin to an interaction skeleton (Roelfsema&Singer, Cereb Cortex, 1998). Apical-basal integration yields an up-modulation in neuron activity binding it to the attended configuration. Gating information from thalamus restricts this integration to task-relevant locations (Saalman&Kastner, Curr Op Neurobiol, 2009). By model simulations, we show how altering the apical compartment\u27s operation regime steers binding to either perform search or incremental grouping

Emphysema and secondary pneumothorax in young adults smoking cannabis

Background: We observed a remarkable increase in the number of young patients who presented with lung emphysema and secondary spontaneous pneumothorax (SSP) at our institution for over a period of 30 months; most of them have a common history of marijuana abuse. Study design: Retrospective case series. Methods: Seventeen young patients presented with spontaneous pneumothorax with bullous lung emphysema were systematically evaluated over a period of 30 months. All were regular marijuana smokers. Clinical history, chest X-ray, CT-scan, lung function test, and laboratory and histological examinations were assessed. We compared the findings of this group (group I) with the findings of non-marijuana smoking patients (group II) in the same period. The findings of this series were also compared with the findings of 75 patients presented with pneumothorax in a previous period from January 2000 till March 2002 (group III). Results: In group I, there were 17 patients: the median age of the patients was 27 years (range 19-43 years), 16 males and 1 female. All were living in Switzerland. All but one smoked marijuana daily for a mean of 8.8 years and tobacco for 11.8 years. CT-scan showed multiple bullae at the apex or significant bullous emphysema with predominance in the upper lobes only in two patients. Only two patients had reduced forced first second expiratory volume (FEV1) and one reduced vital capacity (VC) below the predicted 50%. This correlated with the subjectively asymptomatic condition of the patients. All but two patients were treated by video-assisted thoracoscopic surgery (VATS) for prevention of relapsing pneumothorax. Histology showed severe lung emphysema, inflammation, and heavily pigmented macrophages. In group II, there were 85 patients: there were 78 males, the median age was 24 years (range 17-40 years), 74 patients smoked tobacco for 13.4 years but no marijuana. CT-scan in 72 patients showed only small bullae at the apex but no significant emphysema; other clinical, laboratory, and histopathological findings showed no significant difference in group I. In group III, there were 75 patients: there were 71 males and 4 females. Mean age was 25 years (range 16-46 years). Six smoked marijuana daily for a mean of 3.2 years, and 62 smoked tobacco for 14 years. CT-scan done in 59 patients showed few small bullae at the apex but no significant lung emphysema. The presence of lung emphysema on CT-scan in group I was significantly different than in groups II and III (p = 0.14). No significant difference was found among all groups in the form of clinical, laboratory, and histopathological findings. Conclusions: In case of emphysema in young individuals, marijuana abuse has to be considered in the differential diagnosis. The period of marijuana smoking seems to play an important role in the development of lung emphysema. This obviously quite frequent condition in young and so far asymptomatic patients will have medical, financial, and ethical impact, as some of these patients may be severely handicapped or even become lung transplant candidates in the futur

Study Protocol for a Randomised Controlled Trial on Pulmonary Metastasectomy vs. Standard of Care in Colorectal Cancer Patients With ≥ 3 Lung Metastases (PUCC-Trial)

This is a multicentre prospective randomised controlled trial for patients with 3 or more resectable pulmonary metastases from colorectal carcinoma. The study investigates the effects of pulmonary metastasectomy in addition to standard medical treatment in comparison to standard medical treatment plus possible local ablative measures such as SBRT. This trial is intended to demonstrate an overall survival difference in the group undergoing pulmonary metastasectomy. Further secondary and exploratory endpoints include quality of life (EORTC QLQ-C30, QLQ-CR29 and QLQ-LC29 questionnaires), progression-free survival and impact of mutational status. Due to the heterogeneity and complexity of the disease and treatment trajectories in metastasised colorectal cancer, well powered trials have been very challenging to design and execute. The goal of this study is to create a setting which allows treatment as close to the real life conditions as possible but under well standardised conditions. Based on previous trials, in which patient recruitment in the given setting hindered successful study completion, we decided to (1) restrict inclusion to patients with 3 or more metastases (since in case of lesser, surgery will probably be the preferred option) and (2) allow for real world standard of care (SOC) treatment options before and after randomisation including watchful waiting (as opposed to a predefined treatment protocol) and (3) possibility that patient can receive SOC externally (to reduce patient burden). Moreover, we chose to stipulate 12 weeks of systemic treatment prior to possible resection to further standardize treatment response and disease course over a certain period of time. Hence, included patients will be in the disease state of oligopersistence rather than primary oligometastatic. The trial was registered in the German Clinical Trials Register (DRKS-No.: DRKS00024727)

Dasatinib reverses Cancer-associated Fibroblasts (CAFs) from primary Lung Carcinomas to a Phenotype comparable to that of normal Fibroblasts

Cancer associated fibroblasts (CAFs) play a critical role for growth, invasion, and metastasis of cancer. Therefore, targeting CAFs with small molecule inhibitors may be an attractive anti-tumor strategy. The current study aims to identify small molecule kinase inhibitors affecting CAF's growth and to characterize the biological effects of active compounds on primary CAFs from lung cancer. We screened two individual CAF strains for their sensitivity to a panel of 160 kinase inhibitors. Five kinase inhibitors were identified inhibiting more than 50% of the growth of both cell lines. Three of them were inhibitors of PDGFR at nanomolar concentrations. Therefore, we further tested the FDA approved PDGFR inhibitors Dasatinib, Nilotinib, Sorafenib, and Imatinib. All 37 CAF strains investigated were highly sensitive to Dasatinib at clinically relevant concentrations. Imatinib was slightly less effective, whereas the inhibitory effects of Nilotinib and Sorafenib were significantly less pronounced

Systems analysis of cancer cell heterogeneity in caspase-dependent apoptosis subsequent to mitochondrial outer membrane permeabilization.

Deregulation of apoptosis is a hallmark of carcinogenesis. We here combine live cell imaging and systems modeling to investigate caspase-dependent apoptosis execution subsequent to mitochondrial outer membrane permeabilization (MOMP) in several cancer cell lines. We demonstrate that, although most cell lines that underwent MOMP also showed robust and fast activation of executioner caspases and apoptosis, the colorectal cancer cell lines LoVo and HCT-116 Smac(-/-), similar to X-linked inhibitor of apoptosis protein (XIAP)-overexpressing HeLa (HeLa XIAP(Adv)) cells, only showed delayed and often no caspase activation, suggesting apoptosis impairment subsequent to MOMP. Employing APOPTO-CELL, a recently established model of apoptosis subsequent to MOMP, this impairment could be understood by studying the systemic interaction of five proteins that are present in the apoptosis pathway subsequent to MOMP. Using APOPTO-CELL as a tool to study detailed molecular mechanisms during apoptosis execution in individual cell lines, we demonstrate that caspase-9 was the most important regulator in DLD-1, HCT-116, and HeLa cells and identified additional cell line-specific co-regulators. Developing and applying a computational workflow for parameter screening, systems modeling identified that apoptosis execution kinetics are more robust against changes in reaction kinetics in HCT-116 and HeLa than in DLD-1 cells. Our systems modeling study is the first to draw attention to the variability in cell specific protein levels and reaction rates and to the emergent effects of such variability on the efficiency of apoptosis execution and on apoptosis impairment subsequent to MOMP

Light-field-driven electronics in the mid-infrared regime: Schottky rectification

The speed of an active electronic semiconductor device is limited by RC timescale, i.e., the time required for its charging and discharging. To circumvent this ubiquitous limitation of conventional electronics, we investigate diodes under intense mid-infrared light-field pulses. We choose epitaxial graphene on silicon carbide as a metal/semiconductor pair, acting as an ultrarobust and almost-transparent Schottky diode. The usually dominant forward direction is suppressed, but a characteristic signal occurs in reverse bias. For its theoretical description, we consider tunneling through the light-field–modulated Schottky barrier, complemented by a dynamical accumulation correction. On the basis only of the DC parametrization of the diode, the model provides a consistent and accurate description of the experimentally observed infrared phenomena. This allows the conclusion that cycle-by-cycle dynamics determines rectification. As the chosen materials have proven capabilities for transistors, circuits, and even a full logic, we see a way to establish light-field-driven electronics with rapidly increasing functionality