2,627 research outputs found
Ernst Weiss
No full textDigital ImageThe Austrian author Ernst Weiss was born in 1882 in Brno. He died 1940 in Paris
Harvey Weiss Correspondence
No full textEntries include a typed letter from the Maine State Library to New York children\u27s book author Harvey Weiss introducing the Maine Author Collection and notice that a description of his book would appear in Maine Library Association Bulletin, a typed letter from Weiss on personal stationery presenting a copy of Twenty-Four And Stanley, and a typed letter from the Maine State Library concerning the irrepressible Stanley and on receipt of the book for the Maine Author collection
Malcolm E. and Ann E. Weiss Correspondence
No full textEntry is a typed letter of reply from math and science children\u27s book author Malcolm E. Weiss on his personal stationery concerning a request for a copy of his book 666 Jellybeans! All That? for the Maine Author Collection and additionally the attempt of Weiss to send a copy of a Young Math Series book Solomon Grundy, Born on Oneday from the publisher, a defense for an overdue book, and a list of books written by his wife, history and social studies children\u27s author Ann E. Weiss as well as a list of his own titles at this time
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Single Molecule Spectroscopy for Studying Conformational Dynamics of Short Oligonucleotides
No full textUnderstanding biology at the molecular level has been driving technological advances in biological and medical science for many years. Methods for probing molecular systems are often dependent on sampling the concerted actions of large assemblies of molecules rather than for studying individual molecules operating in isolation. Most methods used in experimental biology are largely insensitive to the activity of a single molecule. Over the past twenty five years, advances in a variety of disciplines have been employed which allow researchers to use single molecule approaches to for examining biomolecules, a development which has had remarkable implications for advancing the understanding of cellular processes. Single molecule techniques have been used to resolve questions about everything from replication, recombination, transcription and translation and protein folding, among other subjects.The structure-function relationship in biology is central to the understanding of cellular processes, and has provided one of the most significant intellectual frameworks for understanding molecular pathways. Its success is validated by numerous studies using X-ray crystallography that now routinely allow researchers to make rational predictions explaining why and how biomolecules interact. The famous "lock and key" model for enzymatic function perhaps best exemplifies this framework. Despite their predictive power, structure-functional relationships often gloss over a basic fact of biological systems--both structure and function may in fact possess a remarkable degree of dynamism. This dissertation summarizes my efforts to develop and refine methods for interrogating the dynamical properties of single molecules, with a particular emphasis on studying structural properties of DNA and examining protein-DNA interactions. I provide an overview of fluorescence, FRET and fluorescence lifetime spectroscopy in Chapter 1, and discuss the methods I developed using fluorescence lifetime to examine conformational fluctuations of sub-persistence length segments of DNA. In Chapter 2, I describe a microfluidic-based platform developed in the Shimon Weiss Lab for conducting single molecule FRET assays, which was used to exploit persistence length changes in DNA upon hybridization to screen context-dependent RNA polymerase transcription. Finally, in Chapter 3, I describe a new detector with improved red spectrum sensitivity, which provides a foundation for further work applying fluorescence lifetime analysis to studying structural perturbations in DNA on nanosecond timescales
Scattering-based super-resolution optical fluctuation imaging
No full textSuper-resolution optical imaging has become a prominent tool in life and material sciences, allowing one to decipher structures at increasingly greater spatial detail. Among the utilized techniques in this field, super-resolution optical fluctuation imaging (SOFI) has proved to be a valuable approach. A major advantage of SOFI is its less restrictive requirements for generating super-resolved images of neighboring nano-structures or molecules, as it only assumes that the detected fluctuating light from neighboring emitters is statistically uncorrelated, but not necessarily separated in time. While most optical super-resolution microscopies depend on signals obtained from fluorescence, they are limited by photobleaching and phototoxicity. An alternative source for optical signals can be acquired by detecting the light scattered from molecules or nanoparticles. However, the application of coherent scattering-based imaging modalities for super-resolution imaging has been considerably limited compared to fluorescence-based modalities. Here, we develop scattering-based super-resolution optical fluctuation imaging (sSOFI), where we utilize the rotation of anisotropic particles as a source of fluctuating optical signals. We discuss the differences in the application of SOFI algorithms for coherent and incoherent imaging modalities and utilize interference microscopy to demonstrate super-resolution imaging of rotating nanoparticle dimers. We present a theoretical analysis of the relevant model systems and discuss the possible effects of cusp artifacts and electrodynamic coupling between nearby nano-scatterers. Finally, we apply sSOFI as a label-free novelty filter that highlights regions with higher activity of biomolecules and demonstrates its use by imaging membrane protrusions of live cells. Overall, the development of optical super-resolution approaches for coherent scattering-based imaging modalities, as described here, could potentially allow for the investigation of biological processes at temporal resolutions and acquisition durations previously inaccessible in fluorescence-based imaging
Measuring diffusion with polarization-modulation dual-focus fluorescence correlation spectroscopy
No full textWe present a new technique, polarization-modulation dual-focus fluorescence correlation spectroscopy (pmFCS), based on the recently introduced dual-focus fluorescence correlation spectroscopy (2fFCS) to measure the absolute value of diffusion coefficients of fluorescent molecules at pico- to nanomolar concentrations. Analogous to 2fFCS, the new technique is robust against optical saturation in yielding correct values of the diffusion coefficient. This is in stark contrast to conventional FCS where optical saturation leads to an apparent decrease in the determined diffusion coefficient with increasing excitation power. However, compared to 2fFCS, the new technique is simpler to implement into a conventional confocal microscope setup and is compatible with cw-excitation, only needing as add-ons an electro-optical modulator and a differential interference contrast prism. With pmFCS, the measured diffusion coefficient (D) for Atto655 maleimide in water at 25oC is determined to be equal to (4.09±0.07)×10-6cm2/s, in good agreement with the value of 4.04×10-6cm2/s as measured by 2fFCS
Achieving increased resolution and more pixels with Superresolution Optical Fluctuation Imaging (SOFI)
No full textSuperresolution Optical Fluctuation Imaging (SOFI) as initially demonstrated allows for a resolution enhancement in imaging by a factor of square-root of two. Here, we demonstrate how to increase the resolution of SOFI images by re-weighting the Optical Transfer Function (OTF). Furthermore, we demonstrate how cross-cumulants can be exploited to obtain a fair approximation of the underlying Point-Spread Function. We show a two-fold increase of resolution (over the diffraction limit) of near-infrared quantum dot labeled tubulin-network of 3T3 fibroblasts
Electrically controlling and optically observing the membrane potential of supported lipid bilayers
No full textSupported lipid bilayers are a well-developed model system for the study of membranes and their associated proteins, such as membrane channels, enzymes, and receptors. These versatile model membranes can be made from various components, ranging from simple synthetic phospholipids to complex mixtures of constituents, mimicking the cell membrane with its relevant physiochemical and molecular phenomena. In addition, the high stability of supported lipid bilayers allows for their study via a wide array of experimental probes. In this work, we describe a platform for supported lipid bilayers that is accessible both electrically and optically, and demonstrate direct optical observation of the transmembrane potential of supported lipid bilayers. We show that the polarization of the supported membrane can be electrically controlled and optically probed using voltage-sensitive dyes. Membrane polarization dynamics is understood through electrochemical impedance spectroscopy and the analysis of an equivalent electrical circuit model. In addition, we describe the effect of the conducting electrode layer on the fluorescence of the optical probe through metal-induced energy transfer, and show that while this energy transfer has an adverse effect on the voltage sensitivity of the fluorescent probe, its strong distance dependency allows for axial localization of fluorescent emitters with ultrahigh accuracy. We conclude with a discussion on possible applications of this platform for the study of voltage-dependent membrane proteins and other processes in membrane biology and surface science
Electrically Controlling and Optically Observing the Membrane Potential of Supported Lipid Bilayers
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