Optically trapped bacteria pairs reveal discrete motile response to control aggregation upon cell–cell approach

Aggregation of bacteria plays a key role in the formation of many biofilms. The critical first step is cell–cell approach, and yet the ability of bacteria to control the likelihood of aggregation during this primary phase is unknown. Here, we use optical tweezers to measure the force between isolated Bacillus subtilis cells during approach. As we move the bacteria towards each other, cell motility (bacterial swimming) initiates the generation of repulsive forces at bacterial separations of ~3 μm. Moreover, the motile response displays spatial sensitivity with greater cell–cell repulsion evident as inter-bacterial distances decrease. To examine the environmental influence on the inter-bacterial forces, we perform the experiment with bacteria suspended in Tryptic Soy Broth, NaCl solution and deionised water. Our experiments demonstrate that repulsive forces are strongest in systems that inhibit biofilm formation (Tryptic Soy Broth), while attractive forces are weak and rare, even in systems where biofilms develop (NaCl solution). These results reveal that bacteria are able to control the likelihood of aggregation during the approach phase through a discretely modulated motile response. Clearly, the force-generating motility we observe during approach promotes biofilm prevention, rather than biofilm formation

Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the treatment of incompletely and completely resected adenoid cystic carcinomas of the head and neck: initial clinical results and toxicity of treatment

BACKGROUND: Presenting the initial clinical results in the treatment of complex shaped adenoid cystic carcinomas (ACC) of the head and neck region by inverse planned stereotactic IMRT. MATERIALS: 25 patients with huge ACC in different areas of the head and neck were treated. At the time of radiotherapy two patients already suffered from distant metastases. A complete resection of the tumor was possible in only 4 patients. The remaining patients were incompletely resected (R2: 20; R1: 1). 21 patients received an integrated boost IMRT (IBRT), which allow the use of different single doses for different target volumes in one fraction. All patients were treated after inverse treatment planning and stereotactic target point localization. RESULTS: The mean folllow-up was 22.8 months (91 – 1490 days). According to Kaplan Meier the three year overall survival rate was 72%. 4 patients died caused by a systemic progression of the disease. The three-year recurrence free survival was according to Kaplan Meier in this group of patients 38%. 3 patients developed an in-field recurrence and 3 patient showed a metastasis in an adjacent lymph node of the head and neck region. One patient with an in-field recurrence and a patient with the lymph node recurrence could be re-treated by radiotherapy. Both patients are now controlled. Acute side effects >Grade II did only appear so far in a small number of patients. CONCLUSION: The inverse planned stereotactic IMRT is feasible in the treatment of ACC. By using IMRT, high control rates and low side effects could by achieved. Further evaluation concerning the long term follow-up is needed. Due to the technical advantage of IMRT this treatment modality should be used if a particle therapy is not available

Small molecule receptor tyrosine kinase inhibitor of platelet-derived growth factor signaling (SU9518) modifies radiation response in fibroblasts and endothelial cells

BACKGROUND: Several small receptor tyrosine kinase inhibitors (RTKI) have entered clinical cancer trials alone and in combination with radiotherapy or chemotherapy. The inhibitory spectrum of these compounds is often not restricted to a single target. For example Imatinib/Gleevec (primarily a bcr/abl kinase inhibitor) or SU11248 (mainly a VEGFR inhibitor) are also potent inhibitors of PDGFR and other kinases. We showed previously that PDGF signaling inhibition attenuates radiation-induced lung fibrosis in a mouse model. Here we investigate effects of SU9518, a PDGFR inhibitor combined with ionizing radiation in human primary fibroblasts and endothelial cells in vitro, with a view on utilizing RTKI for antifibrotic therapy. METHODS: Protein levels of PDGFR-α/-β and phosphorylated PDGFR in fibroblasts were analyzed using western and immunocytochemistry assays. Functional proliferation and clonogenic assays were performed (i) to assess PDGFR-mediated survival and proliferation in fibroblasts and endothelial cells after SU9518 (small molecule inhibitor of PDGF receptor tyrosine kinase); (ii) to test the potency und selectivity of the PDGF RTK inhibitor after stimulation with PDGF isoforms (-AB, -AA, -BB) and VEGF+bFGF. In order to simulate in vivo conditions and to understand the role of radiation-induced paracrine PDGF secretion, co-culture models consisting of fibroblasts and endothelial cells were employed. RESULTS: In fibroblasts, radiation markedly activated PDGF signaling as detected by enhanced PDGFR phosphorylation which was potently inhibited by SU9518. In fibroblast clonogenic assay, SU9518 reduced PDGF stimulated fibroblast survival by 57%. Likewise, SU9518 potently inhibited fibroblast and endothelial cell proliferation. In the co-culture model, radiation of endothelial cells and fibroblast cells substantially stimulated proliferation of non irradiated fibroblasts and vice versa. Importantly, the RTK inhibitor significantly inhibited this paracrine radiation-induced fibroblast and endothelial cell activation. CONCLUSION: Radiation-induced autocrine and paracrine PDGF signaling plays an important role in fibroblast and endothelial cell proliferation. SU9518, a PDGFR tyrosine kinase inhibitor, reduces radiation-induced fibroblast and endothelial cell activation. This may explain therapeutic anticancer effects of Imatinib/Gleevec, and at the same time it could open a way of attenuating radiation-induced fibrosis

EquiFACS: the Equine Facial Action Coding System

Although previous studies of horses have investigated their facial expressions in specific contexts, e.g. pain, until now there has been no methodology available that documents all the possible facial movements of the horse and provides a way to record all potential facial configurations. This is essential for an objective description of horse facial expressions across a range of contexts that reflect different emotional states. Facial Action Coding Systems (FACS) provide a systematic methodology of identifying and coding facial expressions on the basis of underlying facial musculature and muscle movement. FACS are anatomically based and document all possible facial movements rather than a configuration of movements associated with a particular situation. Consequently, FACS can be applied as a tool for a wide range of research questions. We developed FACS for the domestic horse (Equus caballus) through anatomical investigation of the underlying musculature and subsequent analysis of naturally occurring behaviour captured on high quality video. Discrete facial movements were identified and described in terms of the underlying muscle contractions, in correspondence with previous FACS systems. The reliability of others to be able to learn this system (EquiFACS) and consistently code behavioural sequences was high—and this included people with no previous experience of horses. A wide range of facial movements were identified, including many that are also seen in primates and other domestic animals (dogs and cats). EquiFACS provides a method that can now be used to document the facial movements associated with different social contexts and thus to address questions relevant to understanding social cognition and comparative psychology, as well as informing current veterinary and animal welfare practices

Chromosomal radiosensitivity and acute radiation side effects after radiotherapy in tumour patients - a follow-up study

Radiotherapists are highly interested in optimizing doses especially for patients who tend to suffer from side effects of radiotherapy (RT). It seems to be helpful to identify radiosensitive individuals before RT. Thus we examined aberrations in FISH painted chromosomes in in vitro irradiated blood samples of a group of patients suffering from breast cancer. In parallel, a follow-up of side effects in these patients was registered and compared to detected chromosome aberrations. METHODS: Blood samples (taken before radiotherapy) were irradiated in vitro with 3 Gy X-rays and analysed by FISH-painting to obtain aberration frequencies of first cycle metaphases for each patient. Aberration frequencies were analysed statistically to identify individuals with an elevated or reduced radiation response. Clinical data of patients have been recorded in parallel to gain knowledge on acute side effects of radiotherapy. RESULTS: Eight patients with a significantly elevated or reduced aberration yield were identified by use of a t-test criterion. A comparison with clinical side effects revealed that among patients with elevated aberration yields one exhibited a higher degree of acute toxicity and two patients a premature onset of skin reaction already after a cumulative dose of only 10 Gy. A significant relationship existed between translocations in vitro and the time dependent occurrence of side effects of the skin during the therapy period. CONCLUSIONS: The results suggest that translocations can be used as a test to identify individuals with a potentially elevated radiosensitivity

Characterization of dark current signal measurements of the ACCDs used on-board the Aeolus satellite

Even just shortly after the successful launch of the European Space Agency satellite Aeolus in August 2018, it turned out that dark current signal anomalies of single pixels (so-called “hot pixels”) on the accumulation charge-coupled devices (ACCDs) of the Aeolus detectors detrimentally impact the quality of the aerosol and wind products, potentially leading to wind errors of up to several meters per second. This paper provides a detailed characterization of the hot pixels that occurred during the first 1.5 years in orbit. The hot pixels are classified according to their characteristics to discuss their impact on wind measurements. Furthermore, mitigation approaches for the wind retrieval are presented and potential root causes for hot pixel occurrence are discussed. The analysis of the dark current signal anomalies reveals a large variety of anomalies ranging from pixels with random telegraph signal (RTS)-like characteristics to pixels with sporadic shifts in the median dark current signal. Moreover, the results indicate that the number of hot pixels almost linearly increased during the observing period between 2 September 2018 and 20 May 2020 with 6 % of the ACCD pixels affected in total at the end of the period leading to 9.5 % at the end of the mission lifetime. This work introduces dedicated instrument calibration modes and ground processors, which allowed for a correction shortly after a hot pixel occurrence. The achieved performance with this approach avoids risky adjustments to the in-flight hardware operation. It is demonstrated that the success of the correction scheme varies depending on the characteristics of each hot pixel itself. With the herein presented categorization, it is shown that multi-level RTS pixels with high fluctuation are the biggest challenge for the hot pixel correction scheme. Despite a detailed analysis in this framework, no conclusion could be drawn about the root cause of the hot pixel issue

Imbibition in Disordered Media

The physics of liquids in porous media gives rise to many interesting phenomena, including imbibition where a viscous fluid displaces a less viscous one. Here we discuss the theoretical and experimental progress made in recent years in this field. The emphasis is on an interfacial description, akin to the focus of a statistical physics approach. Coarse-grained equations of motion have been recently presented in the literature. These contain terms that take into account the pertinent features of imbibition: non-locality and the quenched noise that arises from the random environment, fluctuations of the fluid flow and capillary forces. The theoretical progress has highlighted the presence of intrinsic length-scales that invalidate scale invariance often assumed to be present in kinetic roughening processes such as that of a two-phase boundary in liquid penetration. Another important fact is that the macroscopic fluid flow, the kinetic roughening properties, and the effective noise in the problem are all coupled. Many possible deviations from simple scaling behaviour exist, and we outline the experimental evidence. Finally, prospects for further work, both theoretical and experimental, are discussed.Comment: Review article, to appear in Advances in Physics, 53 pages LaTe

Confirming chemical clocks: asteroseismic age dissection of the Milky Way disc(s)

Investigations of the origin and evolution of the Milky Way disc have long relied on chemical and kinematic identifications of its components to reconstruct our Galactic past. Difficulties in determining precise stellar ages have restricted most studies to small samples, normally confined to the solar neighbourhood. Here, we break this impasse with the help of asteroseismic inference and perform a chronology of the evolution of the disc throughout the age of the Galaxy. We chemically dissect the Milky Way disc population using a sample of red giant stars spanning out to 2 kpc in the solar annulus observed by the Kepler satellite, with the added dimension of asteroseismic ages. Our results reveal a clear difference in age between the low- and high-α populations, which also show distinct velocity dispersions in the V and W components. We find no tight correlation between age and metallicity nor [α/Fe] for the high-α disc stars. Our results indicate that this component formed over a period of more than 2 Gyr with a wide range of [M/H] and [α/Fe] independent of time. Our findings show that the kinematic properties of young α-rich stars are consistent with the rest of the high-α population and different from the low-α stars of similar age, rendering support to their origin being old stars that went through a mass transfer or stellar merger event, making them appear younger, instead of migration of truly young stars formed close to the Galactic bar

Confirming chemical clocks: asteroseismic age dissection of the Milky Way disk(s)

Investigations of the origin and evolution of the Milky Way disk have long relied on chemical and kinematic identification of its components to reconstruct our Galactic past. Difficulties in determining precise stellar ages have restricted most studies to small samples, normally confined to the solar neighbourhood. Here we break this impasse with the help of asteroseismic inference and perform a chronology of the evolution of the disk throughout the age of the Galaxy. We chemically dissect the Milky Way disk population using a sample of red giant stars spanning out to 2~kpc in the solar annulus observed by the {\it Kepler} satellite, with the added dimension of asteroseismic ages. Our results reveal a clear difference in age between the low- and high-$\alpha$ populations, which also show distinct velocity dispersions in the $V$ and $W$ components. We find no tight correlation between age and metallicity nor [$\alpha$/Fe] for the high-$\alpha$ disk stars. Our results indicate that this component formed over a period of more than 2~Gyr with a wide range of [M/H] and [$\alpha$/Fe] independent of time. Our findings show that the kinematic properties of young $\alpha$-rich stars are consistent with the rest of the high-$\alpha$ population and different from the low-$\alpha$ stars of similar age, rendering support to their origin being old stars that went through a mass transfer or stellar merger event, making them appear younger, instead of migration of truly young stars formed close to the Galactic bar