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Stanford University Department of Applied Physics

Works: 169 works in 169 publications in 1 language and 182 library holdings
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Laser-tissue interactions in retinal photo-thermal therapy : mechanisms and applications by Christopher Koerner Sramek( file )
1 edition published in 2010 in English and held by 2 libraries worldwide
Since its introduction nearly 40 years ago, laser photocoagulation has been the standard of care for treatment of numerous retinal pathologies. Recently, new approaches have been introduced for more selective targeting of various retinal layers, including patterned scanning photocoagulation, selective retinal therapy, and sub-lethal treatment. Despite its broad use in clinical practice, there remains a need for the quantitative description of laser-tissue interactions involved in retinal phototherapy. A unified description of various treatment regimes and associated mechanisms of tissue damage would allow for optimization of laser parameters to improve selectivity and safety of retinal photocoagulation, and for avoidance of undesirable collateral damage. The presented work describes an investigation into the dynamics of the retinal response to hyperthermia and vaporization. A finite-element computational model of photocoagulation and rupture was constructed based on experimental measurements of laser interactions with tissue, and verified in vivo in the millisecond time domain. Two approaches towards improvement of tissue heating uniformity were studied: spatial and temporal modulation of the treatment beam. After optimization using the computational model, beam shaping and pulse modulation systems were constructed. Experimental studies in vivo confirmed improvements in safety of the retinal treatment, potentially allowing for reductions in treatment time, thermal damage extent, and perceived pain. In addition, tissue response to sub-lethal thermal stress in the retina was explored using expression of heat shock protein in an animal model. Computational modeling of the corresponding treatment regime demonstrated that a similar response is likely to occur in clinical application of sub-lethal exposures. Photo-mechanical interactions in the retina were investigated in model systems and in vivo with microsecond-range exposures. The dominant mechanisms of tissue damage were identified and the corresponding limits of the safe therapeutic window were computed over a broad range of pulse durations - from microseconds to seconds. An understanding of the thermal and mechanical interactions involved in laser heating of the retina allows for the realization of safer and more selective treatment regimes. All three mechanisms investigated in the current study -- photocoagulation, photomechanical interactions and sub-lethal hyperthermia -- play a role in clinical treatment. The developed quantitative models of these interactions have immediate applicability to clinical practice, providing guidance towards optimization of retinal phototherapy, evaluation of retinal safety, and development of new clinical applications
Nonreciprocal photonic crystal circuits by Zheng Wang( Archival Material )
1 edition published in 2006 in English and held by 2 libraries worldwide
Bose-einstein condensation in spin dimer compounds by Suchitra E Sebastian( Archival Material )
1 edition published in 2006 in English and held by 2 libraries worldwide
Optical sensor design for advanced drag-free satellites by Graham Scott Allen( Book )
1 edition published in 2009 in English and held by 2 libraries worldwide
Understanding and predicting RNA structure by Yen Ling Adelene Sim( file )
1 edition published in 2012 in English and held by 2 libraries worldwide
RNA is an important biological macromolecule that carries out a variety of roles in the cell. To function, RNA needs to fold into precise three-dimensional structures. Different physical forces like entropy, base-pairing and stacking interactions, tertiary contacts and electrostatics affect this folding process. In the first part of this thesis, we focus on nucleic acid electrostatics; RNA molecules have negatively charged backbones that require counterions to neutralize charge-repulsion and facilitate folding. We discuss the ion conditions necessary for a riboswitch (gene-regulating RNA found on 5' or 3' ends of messenger RNA) folding, studied how the flexibility of single stranded DNA is affected by the presence of different amounts of counterions and present a benchmark experimental dataset that can be used for direct comparison to electrostatic theories. The second part of the thesis deals with computational and analysis tools developed to model and understand nucleic acid systems with the ultimate goal of being able to predict RNA structure. Since RNA typically folds hierarchically, we devised a general hierarchical sampling protocol that naturally explores RNA three-dimensional conformational space efficiently and can be used in concert with any force field, such as an RNA knowledgebased potential that we also discuss in this thesis. Additionally, we examined a clustering method that can assist analysis of structural models. Lastly, we applied our modeling techniques to study simple two-way RNA junctions with all-atom representation, and probed the modeled effects of sterics, chain connectivity and sequence on dynamic RNA behavior
Inhibitory projection neurons in olfactory information processing by Liang Liang( file )
1 edition published in 2013 in English and held by 2 libraries worldwide
Inhibition occurs throughout the nervous system and impacts diverse neuronal processes. In this dissertation, I focus on an inhibitory circuit motif in the Drosophila olfactory system, parallel inhibition, which differs from the classical feed-forward or feedback inhibition. The Drosophila excitatory and GABAergic inhibitory projection neurons (ePNs and iPNs) each receive input from antennal lobe glomeruli and send parallel output to the lateral horn, a higher-order brain center implicated in regulating innate olfactory behavior. By incorporating in vivo two-photon calcium imaging, advanced fly genetics and optogenetic methods to manipulate and record neuronal activity, we find that iPNs selectively suppress food-related odorant responses but spare signals from pheromone channel stimulation when using specific lateral horn neurons as an olfactory readout. Co-applying food odorant does not affect pheromone signal transmission, suggesting that the differential effects likely result from connection specificity of iPNs, rather than a generalized inhibitory tone. Calcium responses in the ePN axon terminals show no detectable suppression by iPNs, arguing against presynaptic inhibition as a primary mechanism. The parallel inhibition motif may provide specificity in inhibition to funnel specific olfactory information, such as food and pheromone, into distinct downstream circuits
Multiphoton interactions with transparent tissues : applications to imaging and surgery by Ilya Toytman( file )
1 edition published in 2010 in English and held by 2 libraries worldwide
Ultrafast lasers offer an advantage of highly localized interactions with transparent materials due to non-linearity of multiphoton processes with laser intensity. Biological and medical applications of these interactions can be nominally divided into two classes: (1) diagnostic imaging and spectroscopy and (2) plasma-mediated surgery. Imaging techniques, such as multiphoton fluorescence, harmonic generation, and stimulated Raman scattering typically employ relatively low power laser sources to avoid damage to the specimens. Surgical applications, on the other hand, rely on formation of plasma at the focus of high peak power laser beam. Current paradigm in applications of multiphoton interactions is based on scanning of a focused beam within the sample in order to image extended areas or produce long cuts point-by-point. We demonstrate several optical systems based on a new paradigm -- distributed multiphoton interactions, where the scanning is reduced or even not required at all. In the area of diagnostic imaging, we have developed and successfully tested a wide-field Coherent Anti-Stokes Raman Scattering (CARS) microscopy technique, which is based on simultaneous imaging of the extended area of the sample. The signal generation relies on the non-phase-matching illumination, and the image acquisition is performed from the entire illuminated area without scanning, using an array detector. We have characterized the spatial and spectral resolution of the method, and demonstrated its chemical selectivity. Optimization of the illumination geometry and proper selection of the wavelengths of the pump and Stokes beams allowed acquisition of the myelin-specific images of nerve tissue with diffraction-limited spatial resolution of 0.5[mu]m. Single-shot imaging capability has been demonstrated on a test sample of polystyrene beads. In surgical applications of ultrafast lasers the extent of the rupture zone in tissue is often determined by dynamics of cavitation bubble resulting from the optical breakdown. Typically tissue cutting is performed point-by-point using a scanning laser. We have studied the possibilities of enhancing the cutting efficiency using two methods. First approach is based on hydrodynamic interactions between two simultaneously created bubbles. A theoretical model of the flow induced by the cavitation bubbles was developed and experimentally verified. Based on experimentally measured rupture threshold strain of a material we derived the shape of the rupture zone for a given distance between the focal spots. We have found that for the threshold strain of 0.7, a continuous cut is 1.35 longer than the one produced by two bubbles applied sequentially. This ratio increases up to 1.7 if a linear series of multiple bubbles is applied simultaneously. Counter-propagating liquid jets forming during collapse of two bubbles in inviscid liquid can increase the rupture zone up to a factor of 2.5. Alternative approach to extending the cutting zone in transparent tissue is based on generation of optical breakdown in a highly elongated zone. By focusing a picosecond laser pulse with a combination of a lens and an axicon we have obtained breakdown zone with aspect ratio of 250:1. The axial intensity distribution was analyzed based on the shape of the resulting cavitation bubble, and was further confirmed by numerical evaluation of a Fresnel diffraction integral. We have optimized the incident laser beam profile to obtain uniform intensity along the breakdown region and to minimize the amount of energy deposited into the sample. We also demonstrate dielectric breakdown and associated cavitation with adjustable length and axial position controlled by modulation of the laser beam profile using an amplitude mask
Design, fabrication and applications of mems tunable blazed gratings by Xiang Li( Archival Material )
1 edition published in 2006 in English and held by 2 libraries worldwide
Detection and quantitative characterization of biomolecular interactions with microfluidic mechanical trapping by Steven Bates( file )
1 edition published in 2010 in English and held by 2 libraries worldwide
In the era of rapid high-throughput DNA sequencing and increasing bioinformatic capabilities to analyze large amounts of biological data, it is especially important to continue to develop high-throughput experimental proteomic methods. Probing physical interactions among proteins and nucleic acids is a powerful approach to gain insight into their functional relationships. Microfluidic tools are of great potential value to this field because they make it possible to run hundreds or thousands of independent experiments in parallel and at a high spatial density. Here I present and explain MITOMI (mechanically induced trapping of molecular interactions), an in vitro method that was initially created to measure the affinities of transcription factors binding to DNA. I contributed to the development of the system so it could be applied to mapping protein-protein interaction networks, and used it to study the interactions of E. coli RNA polymerase in order to better understand the regulation of bacterial transcription. I also extended the utility of MITOMI by adapting it to be able to measure interaction kinetics and to more efficiently measure affinities. With the ability to discover interactions at a large scale and to quantitatively characterize them on the same platform, MITOMI constitutes a valuable contribution to proteomic methodology
Microfluidic and optofluidic investigation of biological macromolecule phase transistions by Aaron Michael Streets( file )
1 edition published in 2012 in English and held by 2 libraries worldwide
Phase transitions are ubiquitous in nature. Fundamental study of phase transition phenomena is a cornerstone of condensed matter physics, and theoretical results in this area guide technology development in material science. Phase transitions also play an important role in biology. Biological macromolecule phase transitions occur in many biological processes, for example the gel-liquid transition in lipid bilayers and amyloid formation in protein aggregation disease. From a technological standpoint, the ability to crystallize proteins has enabled one of the most important advances in biology of the last century: protein structure determination with X-ray crystallography. However, biological macromolecule phase transitions often display stark phenomenological differences from their inorganic analogs. This owes to the sheer size and complexity of proteins and nucleic acid complexes. Macromolecular phase transition theory is rich in subtleties, anecdotal & counter-intuitive results, and often diverges from predictions of classical theory. In addition to developing theory, fundamental study in this area is also critical for improvements in high-throughput crystallography efforts and in understanding mechanisms of devastating neurodegenerative diseases. This thesis approaches the study of macromolecule phase transitions through the development of new measurement technology. In this work, spectroscopic and imaging techniques are combined with microfluidic systems to provide insight into three areas of macromolecule phase transitions. First, dynamic light scattering and microscopy are integrated onto a microfluidic platform to study and optimize protein crystallization. Additionally dynamic light scattering is combined with fluorescence spectroscopy to investigate amyloid fibril aggregation. Finally, a new technology is presented that demonstrates high-throughput mapping of macromolecule structure by integrating single-molecule fluorescence resonance energy transfer spectroscopy with a microfluidic mixing platform. This lab-on-a-chip platform enables examination of conformational transitions in nucleic acids in response to changes in the chemical and molecular environment in order to create a conformational "phase diagram". In addition to presenting new insight into the mechanism of protein crystallization and protein aggregation, this thesis introduces new technologies for studying biological macromolecule phase transitions
Learning networks in biological systems by Bokyung Choi( file )
1 edition published in 2013 in English and held by 2 libraries worldwide
Learning networks from experimental evidence is an important problem to understand many biological systems. With the help of recent technological developments, such as high dimensional flow cytometry and gene expression arrays, a large amount of quality data are available for the task. Many different approaches exist, to model and learn biological networks from such data. Among those, we have developed methods for probabilistic models and differential equation models. The first part of this paper will cover our research on the Gaussian network model learning and its application to recover signal transduction networks. We develop a fast algorithm to learn Gaussian networks from data, based on a novel heuristic. We show that this algorithm can be extended to handle difficult situations such as non-Gaussian noise as well as limited number of simultaneous measurements. The performance of the algorithm against the standard alarm network is showed. Finally we apply the method to learn signal transduction networks from single cell level multi- channel flow cytometry data. We show that the method can recover networks with limited number of channels and non-Gaussian measurement noise. The second part will cover our research on the dynamical model of gene regulation. In this model, gene regulation is represented with differential equations in rational forms. We show that this type of model is able to reflect complex behaviors of gene regulation, compared to other existing models. Reconstucting the structure and parameters of such dynamical model is not triv- ial, given that limited measurability of gene expression. We develop a novel method to recover networks from measurements at so-called perturbed equilibrium. We show that this method can reconstruct gene regulatory networks with well-established ex- perimental designs. Model benchmark based on simulation data will be presented
Probing RNA folding through electrostatic and coarse-grained simulations by Vincent Bangping Chu( file )
1 edition published in 2009 in English and held by 2 libraries worldwide
The discovery by Cech and coworkers that structured RNA molecules could catalyze specific reactions has revolutionized our understanding of RNA's role and place in the biological machinery of life. The notion of understanding RNA folding from a biophysical perspective means understanding the formation of RNA structure in terms of the basic physical forces at play. This thesis describes the the use of electrostatic and coarse grain simulations and associated experiments to investigate different features of RNA folding. Chapter 1 gives an brief introduction to RNA folding, the primary physical forces that influence its formation, and a review of recent advances in our understanding of structure formation in RNA. Chapters 2 and 3 comprise the next section of the thesis and detail advances in our understanding of electrostatic effects around nucleic acids, a topic of great importance in RNA folding. Specifically, chapter 2 presents the development of a size-modified Poisson-Boltzmann theory to help account for the effects of ionic size while chapter 3 presents a critical assessment of the Poisson-Boltzmann description of electrostatic relaxation in tethered duplex model systems. Chapter 4 highlights a general theoretical framework for understanding the combined effects of electrostatics and junction topology on RNA folding stability and specificity. The last section focuses on the use of coarse grained simulation to understand the role of junction topology in shaping the allowed conformational space of the Transactivation Response (TAR) element from the genome of the Human Immunodeficiency Virus (HIV). Though the last section is not, strictly speaking, a study of RNA folding, understanding RNA conformational motion is of critical importance to the question of structure acquisition in RNAs
Virtual scanning tunneling microscopy : a local spectroscopic probe of two-dimensional electron systems by Adam Richard Sciambi( file )
1 edition published in 2012 in English and held by 2 libraries worldwide
Two dimensional electron systems (2DESs) at semiconductor interfaces are a useful medium for studying complex physics due to their very low disorder and relative simplicity. Many interesting effects, such as the quantum Hall effect, have been discovered through transport measurements in such systems. Unfortunately, the interfacial nature of 2DESs and the related surface energy barrier means that directly accessing them from the surface is difficult. This has limited our understanding of theoretically-predicted, spatially-organized effects such Wigner-crystal microemulsions and quantum Hall stripes, which have been probed only indirectly. In this dissertation, we develop a new type of local probe that circumvents the surface barrier by tunneling into a 2DES from a second 2DES grown nearby. The interlayer tunneling happens directly below a scanned metal tip outside the sample, behaving as a virtual tip in a system we call Virtual Scanning Tunneling Microscopy (VSTM). In the first half of the dissertation, we discuss a novel mechanism for tuning tunneling locally between two 2DESs. Its premise is that raising a quantum potential well next to an adjacent barrier is energetically similar to lowering the barrier relative to a fixed well. A lower barrier leads to the quantum well wave function extending into it and to increased tunneling into a second quantum well on the opposite side. We characterize this mechanism in a GaAs-AlGaAs heterostructure as a new type of transistor. In the second half of the dissertation, results from a working VSTM system are presented, with local interlayer tunneling revealing hidden features in the interfaces below the surface
Critical temperature oscillations in superconductor-ferromagnet trilayers by Leonid Litvak( Archival Material )
1 edition published in 2006 in English and held by 2 libraries worldwide
Mechanochemical coupling and structural dynamics in DNA gyrase by Aakash Basu( file )
1 edition published in 2013 in English and held by 2 libraries worldwide
DNA gyrase is a molecular motor that directionally introduces negative supercoils into DNA, serving a function that is critical to most bacterial life. This thesis addresses the question of how gyrase transduces chemical energy stored in ATP into mechanical energy stored in supercoiled DNA. I have investigated how substeps in the ATPase cycle -- ATP binding, hydrolysis and product release -- coordinate structural transitions of the nucleoprotein complex during the course of the supercoiling reaction. Using single-molecule real-time tracking of DNA compaction and rotation, I have characterized the geometry and interconversion dynamics of DNA configurations under different nucleotide conditions. A critical step in the reaction cycle of DNA gyrase involves the formation and manipulation of a chiral wrap in the path of DNA on a scale of ~ 150 base pairs. I show that chiral wrapping is a multistep process that dominates the overall kinetics and is modulated by ATP. My results identify new roles for ATP binding, hydrolysis and product release, and show that nucleotide states in gyrase cannot be uniquely identified with structural intermediates. The work reveals a sophisticated molecular motor in which a conformational landscape of loosely coupled transitions funnels the enzyme toward productive energy transduction
The large hadron collider and models of new physics by Anson Zhao Yu Hook( file )
1 edition published in 2012 in English and held by 1 library worldwide
The Large Hadron Collider (LHC) is pushing the boundaries of the Standard Model of particle physics. Quantum corrections push the mass of the Higgs to be very heavy; If the hints of the Higgs boson now seen at the LHC are in fact the Higgs, the lightness of the Higgs boson must be explained. Supersymmetry provides a natural explanation for the Higgs mass. This thesis discusses two aspects in Supersymmetric theories, how to build them and how to see them
Towards high efficiency and low cost nano-structured III-V solar cells by Gu Anjia( file )
1 edition published in 2011 in English and held by 1 library worldwide
State-of-the-art III-V multijunction solar cells have achieved a record efficiency of 42%, the highest solar-electric conversion efficiency achieved by any technology. This has fueled great interest in the utility sector for large-scale deployment of solar cells. However, III-V solar cells have thus far proven too expensive for widespread terrestrial applications due to the combined cost of substrates, growth processes and materials. Here, we propose a novel III-V solar cell design based on the epitaxial growth of AlGaAs/GaAs on pre-patterned low-cost substrates to provide a path to cost-effective, large-scale deployment. This approach is based on our discovery that the surface kinetics of epitaxial growth by MBE is significantly altered when growing on three dimensional nanostructures instead of planar surfaces. Based on our exploratory results, we present the device design, electrical and optical simulation, and materials growth and device fabrication and characterization of core-shell nanostructured III-V solar cells. We use both bottom-up and top-down approaches to prepare the nanostructured templates in shape of nanowires and nanopyramids. Finite-difference time-domain (FDTD) and Rigorous Coupled Wave Analysis (RCWA) simulation show that the nanostructures have enhanced absorption and much wider incident acceptance angles than their planar counterpart, and outperform planar three-layer anti-reflective coatings. We first demonstrated high quality, single crystal III-V (GaAs and AlGaAs) polar material conformally epi grown on group IV (nanostructured Ge on Si substrate) nonpolar material via MBE and MOVPE (also known as MOCVD) with largely reduced anti-phase domains. We developed complete and mature routines to fabricate a working, single crystalline III-V solar cell on a nanostructured template. The I-V characterization of the fabricated nanostructured GaAs solar cell proves the concept and shows the great potential of making high-efficiency nano-structured III-V solar cells on low-cost substrates
Characterization of a multimode CQED system by Alexander Themis Papageorge( file )
1 edition published in 2016 in English and held by 1 library worldwide
Cavity quantum electrodynamics (CQED) is a proven testbed for studies of the fundamental light- matter interaction and in recent years has become increasingly relevant in quantum simulation. By engineering the electromagnetic properties of the cavity it is possible to tailor unique interatomic interactions resulting in the possibility of observing novel phase-transitions and self-organization phenomena. These transitions distinguish themselves from existing ultra-cold atom optical lattice experiments in that the order exhibited by the atoms is not externally-imposed but emergent in the atom-cavity interaction. Increasing the variety of cavity modes available for crystallization towards a complete basis leads to the possibility of observing quantum soft-condensed matter phenomena like phonons, dislocations, and frustration in this system. This thesis introduces a novel cold-atoms apparatus designed and constructed with the aim of observing and characterizing emergent quantum phenomena. Details of the experimental setup and procedure are presented along with recent experimental and theoretical results pertaining to a novel self-organization phenomenon. Additionally, the technical aspects of an approach to couple light selectively to arbitrary cavity modes using digital holography will be presented. This tool will be useful for seeding the cavity towards, for example, the promotion of self-organization in a particular mode
Advanced single molecule fluorescence analysis and force spectroscopy to understand myosin motors by Jongmin Sung( file )
1 edition published in 2013 in English and held by 1 library worldwide
Myosins are actin-based molecular motor proteins that are associated with numerous cellular functions both in muscle and non-muscle cells. In the past decades, single molecule biophysics has provided many useful in-vitro techniques that enable one to understand detailed molecular mechanisms of myosin-actin interaction. I will describe our results and continuing efforts in (i) single-molecule fluorescence localization analysis with TIRF microscopy, and (ii) single-molecule force spectroscopy with optical traps to understand myosin motors. Our theoretical point-spread function combined with maximum-likelihood-estimation precisely extracts both positions and orientations of fixed fluorescent molecules simultaneously. This approach is now mature as a structural tool, and I have applied it to two examples: myosin V labeled with a fixed dye walking on actin filaments, and dsDNA with two differently colored probes doubly attached to its backbone. We experimentally show that our method is not only precise but also accurate. Familial hypertrophic cardiomyopathies (HCM) are common genetic heart diseases that are often caused by single point mutations, especially in human beta cardiac myosin II. Using an optical trap assay, we found that the human beta cardiac myosin with the R453C HCM-causing mutation produces significantly elevated intrinsic force. We further developed a new method called harmonic force spectroscopy that can extract a force-velocity curve from a single cardiac myosin molecule. We found that a strong-to-weak transition of a cardiac myosin bound to an actin filament is modulated by an external load, which can be explained by simple Arrhenius transition theory
The dynamics of translation initiation and elongation by Albert Tsai( file )
1 edition published in 2013 in English and held by 1 library worldwide
Translation is the final step that converts genetic information into proteins composed of amino acids using the ribosome-- a complex molecular machine that coordinates the kinetics, chemistry, and mechanics necessary to synthesize a polypeptide. Translation is highly dynamic with processes taking place on the microseconds to minutes timescales. Among the different techniques employed to probe the dynamics of translation, single-molecule fluorescence occupies a unique position, being able to track heterogeneous compositional and conformational changes occurring within tens of milliseconds to minutes. Leveraging several fluorescent signals, we probed the dynamics of translation initiation. Instead of a linear pathway, we observed several different pathways all leading to the formation of an elongation competent ribosome complex, with the flux through each modulated by initiation factors, tRNAs, and mRNA sequence. Next, we tracked how the aminoglycoside family of antibiotics inhibits ribosome and tRNA dynamics during peptide synthesis (elongation), concluding that their potency as bactericides stems from kinetically inhibiting elongation. Finally, we transitioned from model systems into observing elongation dynamics on a biologically functional protein stall sequence, SecM. Our results suggest that stalling the ribosome requires several precisely-timed peptide-ribosome interactions and that ribosomes stall in a distribution of locations on the SecM sequence. These results demonstrate the power of single-molecule fluorescence to monitor global translation dynamics, as well as highlighting the importance of the temporal dimension in forming a coherent and global mechanism for translation
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controlled identity Stanford University. School of Humanities and Sciences

Stanford University. Dept. of Applied Physics
Stanford University. School of Humanities and Sciences. Department of Applied Physics
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