Project description:SignificanceMultiphoton microscopy is a powerful imaging tool for biomedical applications. A variety of techniques and respective benefits exist for multiphoton microscopy, but an enhanced resolution is especially desired. Additionally multiphoton microscopy requires ultrafast pulses for excitation, so optimization of the pulse duration at the sample is critical for strong signals.AimWe aim to perform enhanced resolution imaging that is robust to scattering using a structured illumination technique while also providing a rapid and easily repeatable means to optimize group delay dispersion (GDD) compensation through to the sample.ApproachSpatial frequency modulation imaging (SPIFI) is used in two domains: the spatial domain (SD) and the wavelength domain (WD). The WD-SPIFI system is an in-line tool enabling GDD optimization that considers all material through to the sample. The SD-SPIFI system follows and enables enhanced resolution imaging.ResultsThe WD-SPIFI dispersion optimization performance is confirmed with independent pulse characterization, enabling rapid optimization of pulses for imaging with the SD-SPIFI system. The SD-SPIFI system demonstrates enhanced resolution imaging without the use of photon counting enabled by signal to noise improvements due to the WD-SPIFI system.ConclusionsImplementing SPIFI in-line in two domains enables full-path dispersion compensation optimization through to the sample for enhanced resolution multiphoton microscopy.
Project description:Controller motifs are simple biomolecular reaction networks with negative feedback. They can explain how regulatory function is achieved and are often used as building blocks in mathematical models of biological systems. In this paper we perform an extensive investigation into structural identifiability of controller motifs, specifically the so-called basic and antithetic controller motifs. Structural identifiability analysis is a useful tool in the creation and evaluation of mathematical models: it can be used to ensure that model parameters can be determined uniquely and to examine which measurements are necessary for this purpose. This is especially useful for biological models where parameter estimation can be difficult due to limited availability of measureable outputs. Our aim with this work is to investigate how structural identifiability is affected by controller motif complexity and choice of measurements. To increase the number of potential outputs we propose two methods for including flow measurements and show how this affects structural identifiability in combination with, or in the absence of, concentration measurements. In our investigation, we analyze 128 different controller motif structures using a combination of flow and/or concentration measurements, giving a total of 3648 instances. Among all instances, 34% of the measurement combinations provided structural identifiability. Our main findings for the controller motifs include: i) a single measurement is insufficient for structural identifiability, ii) measurements related to different chemical species are necessary for structural identifiability. Applying these findings result in a reduced subset of 1568 instances, where 80% are structurally identifiable, and more complex/interconnected motifs appear easier to structurally identify. The model structures we have investigated are commonly used in models of biological systems, and our results demonstrate how different model structures and measurement combinations affect structural identifiability of controller motifs.
Project description:BACKGROUND: Flow cytometry is a widely used analytical technique for examining microscopic particles, such as cells. The Flow Cytometry Standard (FCS) was developed in 1984 for storing flow data and it is supported by all instrument and third party software vendors. However, FCS does not capture the full scope of flow cytometry (FCM)-related data and metadata, and data standards have recently been developed to address this shortcoming. FINDINGS: The Data Standards Task Force (DSTF) of the International Society for the Advancement of Cytometry (ISAC) has developed several data standards to complement the raw data encoded in FCS files. Efforts started with the Minimum Information about a Flow Cytometry Experiment, a minimal data reporting standard of details necessary to include when publishing FCM experiments to facilitate third party understanding. MIFlowCyt is now being recommended to authors by publishers as part of manuscript submission, and manuscripts are being checked by reviewers and editors for compliance. Gating-ML was then introduced to capture gating descriptions - an essential part of FCM data analysis describing the selection of cell populations of interest. The Classification Results File Format was developed to accommodate results of the gating process, mostly within the context of automated clustering. Additionally, the Archival Cytometry Standard bundles data with all the other components describing experiments. Here, we introduce these recent standards and provide the very first example of how they can be used to report FCM data including analysis and results in a standardized, computationally exchangeable form. CONCLUSIONS: Reporting standards and open file formats are essential for scientific collaboration and independent validation. The recently developed FCM data standards are now being incorporated into third party software tools and data repositories, which will ultimately facilitate understanding and data reuse.
Project description:Model-based drug development (MBDD) is accepted as a vital approach in understanding patients' drug-related benefit and risk by integrating quantitative information integration from diverse sources collected throughout drug development.(1) This perspective introduces the activities of the Drug and Disease Model Resources (DDMoRe) consortium, founded in 2011 through the Innovative Medicines Initiative Joint Undertaking (IMI-JU)(2) as a European public-private partnership to address a lack of common tools, languages, and standards for modeling and simulation (M&S) to improve model-based knowledge integration.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e34; doi:10.1038/psp.2013.10; advance online publication 20 March 2013.
Project description:A light flow controller that can regulate the three-port optical power in both lossless and lossy modus is realized on a programmable multimode waveguide engine. The microheaters on the waveguide chip mimic the tunable "pixels" that can continuously adjust the local refractive index. Compared to the conventional method where the tuning takes place only on single-mode waveguides, the proposed structure is more compact and requires less electrodes. The local index changes in a multimode waveguide can alter the mode numbers, field distribution, and propagation constants of each individual mode, all of which can alter the multimode interference pattern significantly. However, these changes are mostly complex and not governed by analytical equations as in the single-mode case. Though numerical simulations can be performed to predict the device response, the thermal and electromagnetic computing involved is mostly time-consuming. Here, a multi-level search program is developed based on experiments only. It can reach a target output in real time by adjusting the microheaters collectively and iteratively. It can also jump over local optima and further improve the cost function on a global level. With only a simple waveguide structure and four microheaters, light can be routed freely into any of the three output ports with arbitrary power ratios, with and without extra attenuation. This work may trigger new ideas in developing compact and efficient photonic integrated devices for applications in optical communication and computing.
Project description:This work presents the first implementation of cascaded stages for a microfabricated free-flow isoelectric focusing (FF-IEF) device. Both analytical and computational models for IEF suggest device performance will be improved by utilizing multiple stages to reduce device residence time. These models are shown to be applicable by using focusing of small IEF markers as a demonstration. We also show focusing of fluorescently tagged proteins under different channel geometries, with the most efficient focusing occurring in the cascaded design, as predicted by theory. An additional aim of this work is to demonstrate the compatibility of cascaded FF-IEF with common bioanalytical tools. As an example, outlet fractions from cascaded FF-IEF were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Processing of whole cell lysate followed by immunoblotting for cell signaling markers demonstrates the reduction of albumin from samples, as well as the enrichment of apoptotic markers.
Project description:New experimental techniques in epigenomics allow researchers to assay a diversity of highly dynamic features such as histone marks, DNA modifications or chromatin structure. The study of their fluctuations should provide insights into gene expression regulation, cell differentiation and disease. The Ensembl project collects and maintains the Ensembl regulation data resources on epigenetic marks, transcription factor binding and DNA methylation for human and mouse, as well as microarray probe mappings and annotations for a variety of chordate genomes. From this data, we produce a functional annotation of the regulatory elements along the human and mouse genomes with plans to expand to other species as data becomes available. Starting from well-studied cell lines, we will progressively expand our library of measurements to a greater variety of samples. Ensembl's regulation resources provide a central and easy-to-query repository for reference epigenomes. As with all Ensembl data, it is freely available at http://www.ensembl.org, from the Perl and REST APIs and from the public Ensembl MySQL database server at ensembldb.ensembl.org. Database URL: http://www.ensembl.org.
Project description:Renewable energy sources (RESs) have become integral components of power grids, yet their integration presents challenges such as system inertia losses and mismatches between load demand and generation capacity. These issues jeopardize grid stability. To address this, an effective approach is proposed, combining enhanced load frequency control (LFC) (i.e., fuzzy PID- T IλDμ ) with controlled energy storage systems, specifically controlled redox flow batteries (CRFBs), to mitigate uncertainties arising from RES integration. The optimization of this strategy's parameters is achieved using the crayfish optimization algorithm (COA), known for its global optimization capabilities and balance between exploration and exploitation. Performance evaluation against conventional controllers (PID, FO-PID, FO-(PD-PI)) confirms the superiority of the proposed approach in LFC. Extensive testing under various load disturbances, high renewables penetration, and communication delays ensures its effectiveness in minimizing disruptions. Validation using a standardized IEEE 39-bus system further demonstrates its efficiency in power networks grappling with significant renewables penetration. In summary, this integrated strategy presents a robust solution for modern power systems adapting to increasing renewable energy utilization.
Project description:We describe a control algorithm that can improve accuracy and stability of flow regulation in a microfluidic network that uses a conventional pressure pump system. The algorithm enables simultaneous and independent control of fluid flows in multiple micro-channels of a microfluidic network, but does not require any model parameters or tuning process. We investigate robustness and optimality of the proposed control algorithm and those are verified by simulations and experiments. In addition, the control algorithm is compared with a conventional PID controller to show that the proposed control algorithm resolves critical problems induced by the PID control. The capability of the control algorithm can be used not only in high-precision flow regulation in the presence of disturbance, but in some useful functions for lab-on-a-chip devices such as regulation of volumetric flow rate, interface position control of two laminar flows, valveless flow switching, droplet generation and particle manipulation. We demonstrate those functions and also suggest further potential biological applications which can be accomplished by the proposed control framework.
Project description:Scavenged energy from ambient vibrations has become a promising energy supply for autonomous microsystems. However, restricted by device size, most MEMS vibration energy harvesters have much higher resonant frequencies than environmental vibrations, which reduces scavenged power and limits practical applicability. Herein, we propose a MEMS multimodal vibration energy harvester with specifically cascaded flexible PDMS and "zigzag" silicon beams to simultaneously lower the resonant frequency to the ultralow-frequency level and broaden the bandwidth. A two-stage architecture is designed, in which the primary subsystem consists of suspended PDMS beams characterized by a low Young's modulus, and the secondary system consists of zigzag silicon beams. We also propose a PDMS lift-off process to fabricate the suspended flexible beams and the compatible microfabrication method shows high yield and good repeatability. The fabricated MEMS energy harvester can operate at ultralow resonant frequencies of 3 and 23 Hz, with an NPD index of 1.73 μW/cm3/g2 @ 3 Hz. The factors underlying output power degradation in the low-frequency range and potential enhancement strategies are discussed. This work offers new insights into achieving MEMS-scale energy harvesting with ultralow frequency response.