High-resolution imaging of ultracold fermions in microscopically tailored optical potentials

We report on the local probing and preparation of an ultracold Fermi gas on the length scale of one micrometer, i.e. of the order of the Fermi wavelength. The essential tool of our experimental setup is a pair of identical, high-resolution microscope objectives. One of the microscope objectives allows local imaging of the trapped Fermi gas of 6Li atoms with a maximum resolution of 660 nm, while the other enables the generation of arbitrary optical dipole potentials on the same length scale. Employing a 2D acousto-optical deflector, we demonstrate the formation of several trapping geometries including a tightly focussed single optical dipole trap, a 4x4-site two-dimensional optical lattice and a 8-site ring lattice configuration. Furthermore, we show the ability to load and detect a small number of atoms in these trapping potentials. A site separation of down to one micrometer in combination with the low mass of 6Li results in tunneling rates which are sufficiently large for the implementation of Hubbard-models with the designed geometries.Comment: 15 pages, 6 figure

Conduction of Ultracold Fermions Through a Mesoscopic Channel

In a mesoscopic conductor electric resistance is detected even if the device is defect-free. We engineer and study a cold-atom analog of a mesoscopic conductor. It consists of a narrow channel connecting two macroscopic reservoirs of fermions that can be switched from ballistic to diffusive. We induce a current through the channel and find ohmic conduction, even for a ballistic channel. An analysis of in-situ density distributions shows that in the ballistic case the chemical potential drop occurs at the entrance and exit of the channel, revealing the presence of contact resistance. In contrast, a diffusive channel with disorder displays a chemical potential drop spread over the whole channel. Our approach opens the way towards quantum simulation of mesoscopic devices with quantum gases

Mathematical modeling of cell population dynamics in the colonic crypt and in colorectal cancer

Colorectal cancer is initiated in colonic crypts. A succession of genetic mutations or epigenetic changes can lead to homeostasis in the crypt being overcome, and subsequent unbounded growth. We consider the dynamics of a single colorectal crypt by using a compartmental approach [Tomlinson IPM, Bodmer WF (1995) Proc Natl Acad Sci USA 92: 11130-11134], which accounts for populations of stem cells, differential cells, and transit cells. That original model made the simplifying assumptions that each cell popuation divides synchronously, but we relax these assumptions by adopting an age-structured approach that models asynchronous cell division, and by using a continuum model. We discuss two mechanims that could regulate the growth of cell numbers and maintain the equilibrium that is normally observed in the crypt. The first will always maintain an equilibrium for all parameter values, whereas the second can allow unbounded proliferation if the net per capita growth rates are large enough. Results show that an increase in cell renewal, which is equivalent to a failure of programmed cell death or of differentiation, can lead to the growth of cancers. The second model can be used to explain the long lag phases in tumor growth, during which news, higher equilibria are reached, before unlimited growth in cell number ensues

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

Quantum flutter of supersonic particles in one-dimensional quantum liquids

The non-equilibrium dynamics of strongly correlated many-body systems exhibits some of the most puzzling phenomena and challenging problems in condensed matter physics. Here we report on essentially exact results on the time evolution of an impurity injected at a finite velocity into a one-dimensional quantum liquid. We provide the first quantitative study of the formation of the correlation hole around a particle in a strongly coupled many-body quantum system, and find that the resulting correlated state does not come to a complete stop but reaches a steady state which propagates at a finite velocity. We also uncover a novel physical phenomenon when the impurity is injected at supersonic velocities: the correlation hole undergoes long-lived coherent oscillations around the impurity, an effect we call quantum flutter. We provide a detailed understanding and an intuitive physical picture of these intriguing discoveries, and propose an experimental setup where this physics can be realized and probed directly.Comment: 13 pages, 9 figure

Motion artifacts in standard clinical setting obscure disease-specific differences in quantitative susceptibility mapping

PURPOSE: As Quantitative Susceptibility Mapping (QSM) is maturing, more clinical applications are being explored. With this comes the question whether QSM is sufficiently robust and reproducible to be directly used in a clinical setting where patients are possibly not cooperative and/or unable to suppress involuntary movements sufficiently.
 Subjects and Methods: Twenty-nine patients with Alzheimer's Disease (AD), 31 patients with Mild Cognitive Impairment (MCI) and 41 healthy controls (HC) were scanned on a 3T scanner, including a multi-echo gradient-echo sequence for QSM and an inversion-prepared segmented gradient-echo sequence (T1-TFE, MPRAGE). The severity of motion artifacts (excessive/strong /noticeable/invisible) was categorized via visual inspection by two independent raters. Quantitative susceptibility was reconstructed using "Joint background-field removal and segmentation-Enhanced Dipole Inversion" (JEDI), based on segmented subcortical gray-matter regions, as well as using "Morphology Enabled Dipole Inversion" (MEDI). Statistical analysis of the susceptibility maps was performed per region.
 Results: A large fraction of the data showed motion artifacts, visible in both magnitude images and susceptibility maps. No statistically significant susceptibility differences were found between groups including motion-affected data. Considering only subjects without visible motion, a significant susceptibility differences were observed in caudate nucleus as well as in putamen.
 Conclusion: Motion-effects can obscure statistically significant differences in QSM between patients and controls. Additional measures to restrict and/or compensate for subject motion should be taken for QSM in standard clinical settings to avoid risk of false findings.&#13

Machine learning using digitized herbarium specimens to advance phenological research

Machine learning (ML) has great potential to drive scientific discovery by harvesting data from images of herbarium specimens—preserved plant material curated in natural history collections—but ML techniques have only recently been applied to this rich resource. ML has particularly strong prospects for the study of plant phenological events such as growth and reproduction. As a major indicator of climate change, driver of ecological processes, and critical determinant of plant fitness, plant phenology is an important frontier for the application of ML techniques for science and society. In the present article, we describe a generalized, modular ML workflow for extracting phenological data from images of herbarium specimens, and we discuss the advantages, limitations, and potential future improvements of this workflow. Strategic research and investment in specimen-based ML methods, along with the aggregation of herbarium specimen data, may give rise to a better understanding of life on Earth

Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation

Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum

A novel technique for an alignment-insensitive density calibration of Thomson scattering diagnostics developed at W7-X

In most laboratory setups in plasma physics, including magnetic-confinement experiments for fusion research, laser-based Thomson scattering allows for absolutely calibrated density measurements without input from other diagnostics and with high spatial resolution. A common issue is the alignment stability of either the laser beam or the observation optics. Frequent recalibrations are typically required. This is a challenge in particular for larger fusion experiments; while beam paths tend to get longer, the access for alignment and calibration gets more restricted. Therefore, simple, fast and robust calibration methods are required. A novel calibration technique has been developed at W7-X to account for alignment variations in the calibration procedure. This will decrease the pulse-to-pulse variations significantly and allow for a longer time duration before a recalibration becomes necessary. By monitoring the beam position accurately, it could be shown that misalignment leads to deterministic and reproducible changes in the measured density. The introduced density errors can be corrected for by monitoring the laser beam for every individual laser pulse. In the last experimental campaign, this has been done retrospectively by introducing parallel shifts to the laser beam path in order to show the feasibility of this method. It could be demonstrated that the impact of introduced shifts on the electron density can be successfully corrected for. For future campaigns, the beam alignment will intentionally be varied during the absolute calibration in order to cover the full range of expected beam positions. During the actual experiments, the beam positions will be monitored likewise and each density profile will be evaluated with the most suitable calibration factor. While probably not needed for W7-X, vibrations of the observation optics could be included in the same way.EC/H2020/633053/EU/Implementation of activities described in the Roadmap to Fusion during Horizon 2020 through a Joint programme of the members of the EUROfusion consortium/Eurato