Extended Kramers-Moyal analysis applied to optical trapping

The Kramers-Moyal analysis is a well established approach to analyze stochastic time series from complex systems. If the sampling interval of a measured time series is too low, systematic errors occur in the analysis results. These errors are labeled as finite time effects in the literature. In the present article, we present some new insights about these effects and discuss the limitations of a previously published method to estimate Kramers-Moyal coefficients at the presence of finite time effects. To increase the reliability of this method and to avoid misinterpretations, we extend it by the computation of error estimates for estimated parameters using a Monte Carlo error propagation technique. Finally, the extended method is applied to a data set of an optical trapping experiment yielding estimations of the forces acting on a Brownian particle trapped by optical tweezers. We find an increased Markov-Einstein time scale of the order of the relaxation time of the process which can be traced back to memory effects caused by the interaction of the particle and the fluid. Above the Markov-Einstein time scale, the process can be very well described by the classical overdamped Markov model for Brownian motion.Comment: 14 pages, 18 figure

Stereotactic MRI-guided radiation therapy for localized prostate cancer (SMILE): a prospective, multicentric phase-II-trial

BACKGROUND Normofractionated radiation regimes for definitive prostate cancer treatment usually extend over 7-8 weeks. Recently, moderate hypofractionation with doses per fraction between 2.2 and 4 Gy has been shown to be safe and feasible with oncologic non-inferiority compared to normofractionation. Radiobiologic considerations lead to the assumption that prostate cancer might benefit in particular from hypofractionation in terms of tumor control and toxicity. First data related to ultrahypofractionation demonstrate that the overall treatment time can be reduced to 5-7 fractions with single doses > 6 Gy safely, even with simultaneous focal boosting of macroscopic tumor(s). With MR-guided linear accelerators (MR-linacs) entering clinical routine, invasive fiducial implantations become unnecessary. The aim of the multicentric SMILE study is to evaluate the use of MRI-guided stereotactic radiotherapy for localized prostate cancer in 5 fractions regarding safety and feasibility. METHODS The study is designed as a prospective, one-armed, two-stage, multi-center phase-II-trial with 68 patients planned. Low- and intermediate-risk localized prostate cancer patients will be eligible for the study as well as early high-risk patients (cT3a and/or Gleason Score ≤ 8 and/or PSA ≤ 20 ng/ml) according to d'Amico. All patients will receive definitive MRI-guided stereotactic radiation therapy with a total dose of 37.5 Gy in 5 fractions (single dose 7.5 Gy) on alternating days. A focal simultaneous integrated boost to MRI-defined tumor(s) up to 40 Gy can optionally be applied. The primary composite endpoint includes the assessment of urogenital or gastrointestinal toxicity ≥ grade 2 or treatment-related discontinuation of therapy. The use of MRI-guided radiotherapy enables online plan adaptation and intrafractional gating to ensure optimal target volume coverage and protection of organs at risk. DISCUSSION With moderate hypofractionation being the standard in definitive radiation therapy for localized prostate cancer at many institutions, ultrahypofractionation could be the next step towards reducing treatment time without compromising oncologic outcomes and toxicities. MRI-guided radiotherapy could qualify as an advantageous tool as no invasive procedures have to precede in therapeutic workflows. Furthermore, MRI guidance combined with gating and plan adaptation might be essential in order to increase treatment effectivity and reduce toxicity at the same time

How does cloud-radiative heating over the North Atlantic change with grid spacing, convective parameterization, and microphysics scheme in ICON version 2.1.00?

Cloud-radiative heating (CRH) within the atmosphere and its changes with warming affect the large-scale atmospheric winds in a myriad of ways, such that reliable predictions and projections of circulation require reliable calculations of CRH. In order to assess the sensitivities of upper-tropospheric midlatitude CRH to model settings, we perform a series of simulations with the ICOsahedral Nonhydrostatic Model (ICON) over the North Atlantic using six different grid spacings, parameterized and explicit convection, and one- versus two-moment cloud microphysics. While sensitivity to grid spacing is limited, CRH profiles change dramatically with microphysics and convection schemes. These dependencies are interpreted via decomposition into cloud classes and examination of cloud properties and cloud-controlling factors within these different classes. We trace the model dependencies back to differences in the mass mixing ratios and number concentrations of cloud ice and snow, as well as vertical velocities. Which frozen species are radiatively active and the broadening of the vertical velocity distribution with explicit convection turn out to be crucial factors in altering the modeled CRH profiles.</p

Phytochrome-Based Extracellular Matrix with Reversibly Tunable mechanical Properties

Interrogation and control of cellular fate and function using optogenetics is providing revolutionary insights into biology. Optogenetic control of cells is achieved by coupling genetically encoded photoreceptors to cellular effectors and enables unprecedented spatiotemporal control of signaling processes. Here, a fast and reversibly switchable photoreceptor is used to tune the mechanical properties of polymer materials in a fully reversible, wavelength‐specific, and dose‐ and space‐controlled manner. By integrating engineered cyanobacterial phytochrome 1 into a poly(ethylene glycol) matrix, hydrogel materials responsive to light in the cell‐compatible red/far‐red spectrum are synthesized. These materials are applied to study in human mesenchymal stem cells how different mechanosignaling pathways respond to changing mechanical environments and to control the migration of primary immune cells in 3D. This optogenetics‐inspired matrix allows fundamental questions of how cells react to dynamic mechanical environments to be addressed. Further, remote control of such matrices can create new opportunities for tissue engineering or provide a basis for optically stimulated drug depots

MR-guidance in clinical reality: current treatment challenges and future perspectives

Magnetic Resonance-guided radiotherapy (MRgRT) marks the beginning of a new era. MR is a versatile and suitable imaging modality for radiotherapy, as it enables direct visualization of the tumor and the surrounding organs at risk. Moreover, MRgRT provides real-time imaging to characterize and eventually track anatomical motion. Nevertheless, the successful translation of new technologies into clinical practice remains challenging. To date, the initial availability of next-generation hybrid MR-linac (MRL) systems is still limited and therefore, the focus of the present preview was on the initial applicability in current clinical practice and on future perspectives of this new technology for different treatment sites. MRgRT can be considered a groundbreaking new technology that is capable of creating new perspectives towards an individualized, patient-oriented planning and treatment approach, especially due to the ability to use daily online adaptation strategies. Furthermore, MRL systems overcome the limitations of conventional image-guided radiotherapy, especially in soft tissue, where target and organs at risk need accurate definition. Nevertheless, some concerns remain regarding the additional time needed to re-optimize dose distributions online, the reliability of the gating and tracking procedures and the interpretation of functional MR imaging markers and their potential changes during the course of treatment. Due to its continuous technological improvement and rapid clinical large-scale application in several anatomical settings, further studies may confirm the potential disruptive role of MRgRT in the evolving oncological environment