Ab initio RNA folding

RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, experimental determination of RNA structures through X-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding.Comment: 28 pages, 18 figure

A micromirror array with annular partitioning for high-speed random-access axial focusing

Dynamic axial focusing functionality has recently experienced widespread incorporation in microscopy, augmented/virtual reality (AR/VR), adaptive optics, and material processing. However, the limitations of existing varifocal tools continue to beset the performance capabilities and operating overhead of the optical systems that mobilize such functionality. The varifocal tools that are the least burdensome to drive (ex: liquid crystal, elastomeric or optofluidic lenses) suffer from low (~ 100 Hz) refresh rates. Conversely, the fastest devices sacrifice either critical capabilities such as their dwelling capacity (ex: acoustic gradient lenses or monolithic micromechanical mirrors) or low operating overhead (e.g., deformable mirrors). Here, we present a general-purpose random-access axial focusing device that bridges these previously conflicting features of high speed, dwelling capacity and lightweight drive by employing low-rigidity micromirrors that exploit the robustness of defocusing phase profiles. Geometrically, the device consists of an 8.2 mm diameter array of piston-motion and 48 um-pitch micromirror pixels that provide 2pi phase shifting for wavelengths shorter than 1 100 nm with 10-90 % settling in 64.8 us (i.e., 15.44 kHz refresh rate). The pixels are electrically partitioned into 32 rings for a driving scheme that enables phase-wrapped operation with circular symmetry and requires less than 30 V per channel. Optical experiments demonstrated the array's wide focusing range with a measured ability to target 29 distinct, resolvable depth planes. Overall, the features of the proposed array offer the potential for compact, straightforward methods of tackling bottlenecked applications including high-throughput single-cell targeting in neurobiology and the delivery of dense 3D visual information in AR/VR.Comment: 38 pages, 8 figure

Systems modeling of white matter microstructural abnormalities in Alzheimer's disease

INTRODUCTION: Microstructural abnormalities in white matter (WM) are often reported in Alzheimer's disease (AD). However, it is unclear which brain regions have the strongest WM changes in presymptomatic AD and what biological processes underlie WM abnormality during disease progression. METHODS: We developed a systems biology framework to integrate matched diffusion tensor imaging (DTI), genetic and transcriptomic data to investigate regional vulnerability to AD and identify genetic risk factors and gene subnetworks underlying WM abnormality in AD. RESULTS: We quantified regional WM abnormality and identified most vulnerable brain regions. A SNP rs2203712 in CELF1 was most significantly associated with several DTI-derived features in the hippocampus, the top ranked brain region. An immune response gene subnetwork in the blood was most correlated with DTI features across all the brain regions. DISCUSSION: Incorporation of image analysis with gene network analysis enhances our understanding of disease progression and facilitates identification of novel therapeutic strategies for AD

Deployable reflector antenna performance optimization using automated surface correction and array-feed compensation

Methods for increasing the electromagnetic (EM) performance of reflectors with rough surfaces were tested and evaluated. First, one quadrant of the 15-meter hoop-column antenna was retrofitted with computer-driven and controlled motors to allow automated adjustment of the reflector surface. The surface errors, measured with metric photogrammetry, were used in a previously verified computer code to calculate control motor adjustments. With this system, a rough antenna surface (rms of approximately 0.180 inch) was corrected in two iterations to approximately the structural surface smoothness limit of 0.060 inch rms. The antenna pattern and gain improved significantly as a result of these surface adjustments. The EM performance was evaluated with a computer program for distorted reflector antennas which had been previously verified with experimental data. Next, the effects of the surface distortions were compensated for in computer simulations by superimposing excitation from an array feed to maximize antenna performance relative to an undistorted reflector. Results showed that a 61-element array could produce EM performance improvements equal to surface adjustments. When both mechanical surface adjustment and feed compensation techniques were applied, the equivalent operating frequency increased from approximately 6 to 18 GHz

Design of LCOS microdisplay backplanes for projection applications

De evolutie van licht emitterende diodes (LED) heeft ervoor gezorgd dat het op dit moment interessant wordt om deze componenten als lichtbron te gebruiken in projectiesystemen. LED’s hebben belangrijke voordelen vergeleken met klassieke booglampen. Ze zijn compact, ze hebben een veel grotere levensduur en ogenblikkelijke schakeltijden, ze werken op lage spanningen, etc. LED’s zijn smalbandig en kunnen een groterekleurenbereik realiseren. Ze hebben momenteel echter een beperkte helderheid. Naast de lichtbron is het type van de lichtklep ook bepalend voor de kwaliteit van een projectiesysteem. Er bestaan verschillende lichtkleptechnologieën waaronder die van de reflectieve LCOS-panelen. Deze lichtkleppen kunnen zeer hoge resoluties hebben en wordenvaak gebruikt in kwalitatieve, professionele projectiesystemen. LED’s zijn echter totaal verschillend van booglampen. Ze hebben een andere vorm, package, stralingspatroon, aansturing, fysische en thermische eigenschappen, etc. Hoewel er een twintigtal optische architecturen bekend zijn voor reflectieve beeldschermen (met een booglamp als lichtbron), zijn ze niet geschikt voor LED-projectoren en moeten nieuwe optische architecturen en een elektronische aansturing ontwikkeld worden. In dit doctoraat werd er hieromtrent onderzoek gedaan. Er werd uiteindelijk een driekleurenprojector (R, G, B) met een efficiënt LED-belichtingssysteem gebouwd met twee LCOS-lichtkleppen. Deze LEDprojector heeft superieure eigenschappen (zeer lange levensduur, beeldkwaliteit, etc.) en een matige lichtopbrengst