Protein Docking by the Underestimation of Free Energy Funnels in the Space of Encounter Complexes

Similarly to protein folding, the association of two proteins is driven by a free energy funnel, determined by favorable interactions in some neighborhood of the native state. We describe a docking method based on stochastic global minimization of funnel-shaped energy functions in the space of rigid body motions (SE(3)) while accounting for flexibility of the interface side chains. The method, called semi-definite programming-based underestimation (SDU), employs a general quadratic function to underestimate a set of local energy minima and uses the resulting underestimator to bias further sampling. While SDU effectively minimizes functions with funnel-shaped basins, its application to docking in the rotational and translational space SE(3) is not straightforward due to the geometry of that space. We introduce a strategy that uses separate independent variables for side-chain optimization, center-to-center distance of the two proteins, and five angular descriptors of the relative orientations of the molecules. The removal of the center-to-center distance turns out to vastly improve the efficiency of the search, because the five-dimensional space now exhibits a well-behaved energy surface suitable for underestimation. This algorithm explores the free energy surface spanned by encounter complexes that correspond to local free energy minima and shows similarity to the model of macromolecular association that proceeds through a series of collisions. Results for standard protein docking benchmarks establish that in this space the free energy landscape is a funnel in a reasonably broad neighborhood of the native state and that the SDU strategy can generate docking predictions with less than 5 � ligand interface Ca root-mean-square deviation while achieving an approximately 20-fold efficiency gain compared to Monte Carlo methods.

Singing Through Struggle: Music as a Mode of Cultural Exchange in African American Border City Churches After Emancipation, 1862-1890

This project investigates how religious music, invested with symbolic and cultural meaning, provided African Americans in border city churches with a way to negotiate conflict, assert individual values, and establish a collective identity in the post- emancipation era. In order to focus on the encounter between former slaves and free Blacks, the dissertation examines black churches that received large numbers of southern migrants during and after the Civil War. Primarily a work of history, the study also employs insights and conceptual frameworks from other disciplines including anthropology and ritual studies, African American studies, aesthetic theory, and musicology. It is a work of historical reconstruction in the tradition of scholarship that some have called "lived religion." Chapter 1 introduces the dissertation topic and explains how it contributes to scholarship. Chapter 2 examines social and religious conditions African Americans faced in Baltimore, MD, Philadelphia, PA, and Washington, DC to show why the Black Church played a key role in African Americans' adjustment to post-emancipation life. Chapter 3 compares religious slave music and free black church music to identify differences and continuities between them, as well as their functions in religious settings. Chapters 4, 5, and 6 present case studies on Bethel African Methodist Episcopal Church (Baltimore), Zoar Methodist Episcopal Church (Philadelphia), and St. Luke’s Protestant Episcopal Church (Washington, DC), respectively. Informed by fresh archival materials, the dissertation shows how each congregation used its musical life to uphold values like education and community, to come to terms with a shared experience, and to confront or avert authority when cultural priorities were threatened. By arguing over musical choices or performance practices, or agreeing on mutually appealing musical forms like the gospel songs of the Sunday school movement, African Americans forged lively faith communities and distinctive cultures in otherwise adverse environments. The study concludes that religious music was a crucial form of African American discourse and expression in the post-emancipation era. In the Black Church, it nurtured an atmosphere of exchange, gave structure and voice to conflict, helped create a public sphere, and upheld the values of black people.

Peace and Peacemaking in Paul Against the Backdrop of Greco-Roman Conceptions of Peace

Peace in the ancient world has been studied primarily from the perspective of pacifism and questions related to war and peace. This study employs a socio-historical method to determine how peace was understood in itself, not just with respect to war. It demonstrates that the Greco-Roman world viewed peace as brief periods of tranquility in an existence where conflict was the norm, while Paul regarded peace as the norm and conflict as an intrusive aberration. Through a historical and literary survey of Greco-Roman thought and culture, this study shows that myth, legend, religion, education, philosophy, and science created and perpetuated the idea that conflict was necessary for existence. Wars were fought to attain peace, which meant periods of calm, quiet, and security with respect to the gods, one's inner self, nature, others who are insiders, and others who are outsiders. Despite the desirability of peace, genuine peace was seldom experienced, and even then, only briefly, as underlying enmity persisted without resolution. While Paul supports the prevailing conception of peace as tranquility and felicity in relation to God, self, nature, and others, he differs as to the origin, attainment, and maintenance of peace. In Paul, peace originates in God and is graciously given to those who are justified and reconciled to God through Jesus Christ. God removes the enmity caused by sin and provides the indwelling Spirit to empower believers to think and behave in ways that promote and maintain peace. This study also examines how three social dynamics (honor-shame, patron-client, friendship-enmity) affect Paul's approach to conflict resolution with Philemon and Onesimus, Euodia and Syntyche, believers who are prosecuting one another in civil courts, and Peter. Rather than giving specific procedures for resolving conflict, Paul reinforces the believer's new identity in Christ and the implications of God's grace, love, and peace upon their thoughts, words, and behavior toward one another. Paul uses these three social dynamics to encourage believers in the right direction, but their ultimate accountability is to God. The study concludes with four strategic principles for educating the church and developing an atmosphere and attitude within the church for peacemaking.

APPLICATION OF THE KHOKHLOV-ZABOLOTSKAYA-KUZNETSOV EQUATION TO MODELING HIGH-INTENSITY FOCUSED ULTRASOUND BEAMS

High-intensity focused ultrasound is a form of therapeutic ultrasound which uses high amplitude acoustic waves to heat and ablate tissue. HIFU employs acoustic amplitudes that are high enough that nonlinear propagation effects are important in the evolution of the sound field. A common model for HIFU beams is the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation which accounts for nonlinearity, diffraction, and absorption. The KZK equation models diffraction using the parabolic or paraxial approximation. Many HIFU sources have an aperture diameter similar to the focal length and the paraxial approximation may not be appropriate. Here, results obtained using the “Texas code,” a time-domain numerical solution to the KZK equation, were used to assess when the KZK equation can be employed. In a linear water case comparison with the O’Neil solution, the KZK equation accurately predicts the pressure field in the focal region. The KZK equation was also compared to simulations of the exact fluid dynamics equations (no paraxial approximation). The exact equations were solved using the Fourier-Continuation (FC) method to approximate derivatives in the equations. Results have been obtained for a focused HIFU source in tissue. For a low focusing gain transducer (focal length 50λ and radius 10λ), the KZK and FC models showed excellent agreement, however, as the source radius was increased to 30λ, discrepancies started to appear. Modeling was extended to the case of tissue with the appropriate power law using a relaxation model. The relaxation model resulted in a higher peak pressure and a shift in the location of the peak pressure, highlighting the importance of employing the correct attenuation model. Simulations from the code that were compared to experimental data in water showed good agreement through the focal plane.

PHOTOREFRACTIVE CRYSTAL-BASED ACOUSTO-OPTIC IMAGING IN THE NEAR-INFRARED AND ITS APPLICATIONS

Acousto-optic (AO) sensing and imaging (AOI) is a dual-wave modality that combines ultrasound with diffusive light to measure and/or image the optical properties of optically diffusive media, including biological tissues such as breast and brain. The light passing through a focused ultrasound beam undergoes a phase modulation at the ultrasound frequency that is detected using an adaptive interferometer scheme employing a GaAs photorefractive crystal (PRC). The PRC-based AO system operating at 1064 nm is described, along with the underlying theory, validating experiments, characterization, and optimization of this sensing and imaging apparatus. The spatial resolution of AO sensing, which is determined by spatial dimensions of the ultrasound beam or pulse, can be sub-millimeter for megahertz-frequency sound waves.A modified approach for quantifying the optical properties of diffuse media with AO sensing employs the ratio of AO signals generated at two different ultrasound focal pressures. The resulting “pressure contrast signal” (PCS), once calibrated for a particular set of pressure pulses, yields a direct measure of the spatially averaged optical transport attenuation coefficient within the interaction volume between light and sound. This is a significant improvement over current AO sensing methods since it produces a quantitative measure of the optical properties of optically diffuse media without a priori knowledge of the background illumination. It can also be used to generate images based on spatial variations in both optical scattering and absorption. Finally, the AO sensing system is modified to monitor the irreversible optical changes associated with the tissue heating from high intensity focused ultrasound (HIFU) therapy, providing a powerful method for noninvasively sensing the onset and growth of thermal lesions in soft tissues. A single HIFU transducer is used to simultaneously generate tissue damage and pump the AO interaction. Experimental results performed in excised chicken breast demonstrate that AO sensing can identify the onset and growth of lesion formation in real time and, when used as feedback to guide exposure parameters, results in more predictable lesion formation.

Narratives of Holiness Identity: The "Sanctified Person" in the Church of the Nazarene

This dissertation is an exercise in practical theology, which investigates and responds to the problem of changing holiness identity in the Church of the Nazarene. The first part of the study is an empirical investigation into the social context of contemporary Nazarene holiness identity and practices among Nazarenes in three congregations located in the Northeast United States. Previous research relied too heavily on secularization and sect-church theory to understand the dynamics of religious identity change among Nazarenes. The theological result was a pessimistic appraisal of the future possibilities of holiness identity and practice in the Church of the Nazarene. This study employs an alternative theory—Nancy T. Ammerman's theory of narrative religious identity—to understand the dynamics of lived religious life within these congregations and to identify the various holiness narratives at play. Ammerman's theory facilitates an empirical description of the multiple holiness identities emerging out of the social contexts of these Nazarene congregations and offers a way to account for identity change. At the heart of this research is the theoretical notion that a particular religious identity, in the case of the Church of the Nazarene, the "sanctified person," emerges out of a particular ecclesial context characterized by religious narratives and practices that shape this identity. Chapter one reviews the problem of holiness identity in the Church of the Nazarene and offers an analysis of recent sociological attempts to understand the changing identity among Nazarenes. Chapter two draws on sociological research to describe and depict the range of views of holiness held by some contemporary Nazarenes. Chapter three identifies the varieties of holiness identity within the three Nazarene congregations that are part of the study. Chapter four investigates the social sources that shape the various holiness identities discovered in these congregations. Chapter five is a description of the many ways religious narratives are enacted and engaged within these congregations. The second part of the study is a theological critique of contemporary Nazarene holiness identity. Chapter six draws on the theory of narrative identity proposed by Nancy Ammerman and outlines a theoretical model which describes the social conditions necessary to shape holiness identity, "the sanctified person," within the context of the local congregation. Finally, chapter seven draws on the theological resources of Mennonite scholar and historian John Howard Yoder to propose a way of construing and facilitating holiness identity formation that takes the ecclesiality of hoilness more seriously, emphasizes a clearer relationship between Jesus and the "Christlikeness" that is central to holiness, and highlights the importance of religious practices in the formation of a holiness identity.

Reading Between the Lines: The Potential of Popular Young Adult Fiction in Adolescent Spiritual Formation

Popular culture is a powerful, shaping force in the lives of teenagers between the ages of fourteen through eighteen in the United States today. This dissertation argues the importance of popular fiction for adolescent spiritual formation and it investigates that importance by exploring the significance of narrative for theology and moral formation. The dissertation employs mythic and archetypal criticism as a tool for informing the selection and critique of narratives for use in adolescent spiritual development and it also incorporates insights gained from developmental psychology to lay the groundwork for the development of a curriculum that uses young adult fiction in a program of spiritual formation for teenagers in a local church setting. The dissertation defends the power of narrative in Christian theology and concludes that narrative shapes the imagination in ways that alter perception and are important for the faith life of teenagers in particular. I go on to argue that not all narratives are created equal. In using literary myth criticism in concert with theology, I use the two disciplines’ different aims and methods to fully flesh out the potential of theologies intrinsic to works meant for a largely secular audience. The dissertation compares various works of young adult fiction (M.T. Anderson’s Feed and Terry Pratchett’s Nation in dialogue with a theology of creation; Marcus Zusak’s I am the Messenger and Jerry Spinelli’s Stargirl in dialogue with salvation and saviors; and the four novels of Stephanie Meyer’s Twilight saga in dialogue with a theology of hope (eschatology). The dissertation explores how each theme surfaces (even if only implicitly) from both literary and theological standpoints. The dissertation concludes with a sample four-week lesson plan that demonstrates one way the theological and literary critique can be formed into a practical curriculum for use in an adolescent spiritual development setting. Ultimately, this dissertation provides a framework for how practitioners of young adult formation can select, analyze, and develop materials for their teenagers using new works of popular young adult fiction. The dissertation comes to the conclusion that popular fiction contains a wealth of material that can challenge and shape young readers’ own emerging theology.

Making Sadza with Deaf Zimbabwean Women: A Missiological Reorientation of Practical Theological Method toward Self-Theologizing Agency among Subaltern Communities

Missiological calls for self-theologizing among faith communities present the field of practical theology with a challenge to develop methodological approaches that address the complexities of cross-cultural, practical theological research. Although a variety of approaches can be considered critical correlative practical theology, existing methods are often built on assumptions that limit their use in subaltern contexts. This study seeks to address these concerns by analyzing existing theological methodologies with sustained attention to a community of Deaf Zimbabwean women struggling to develop their own agency in relation to child rearing practices. This dilemma serves as an entry point to an examination of the limitations of existing methodologies and a constructive, interdisciplinary theological exploration. The use of theological modeling methodology employs my experience of learning to cook sadza, a staple dish of Zimbabwe, as a guide for analyzing and reorienting practical theological methodology. The study explores a variety of theological approaches from practical theology, mission oriented theologians, theology among Deaf communities, and African women’s theology in relationship to the challenges presented by subaltern communities such as Deaf Zimbabwean women. Analysis reveals that although there is much to commend in these existing methodologies, questions about who does the critical correlation, whose interests are guiding the study, and consideration for the cross-cultural and power dynamics between researchers and faith communities remain problematic for developing self-theologizing agency. Rather than frame a comprehensive methodology, this study proposes three attitudes and guideposts to reorient practical theological researchers who wish to engender self-theologizing agency in subaltern communities. The creativity of enacted theology, the humility of using checks and balances in research methods, and the grace of finding strategies to build bridges of commonality and community offer ways to reorient practical theological methodologies toward the development of self-theologizing agency among subaltern people. This study concludes with discussion of how these guideposts can not only benefit particular work with a community of Deaf Zimbabwean women, but also provide research and theological reflection in other subaltern contexts.

Search by Shape Examples: Modeling Nonrigid Deformation

We describe our work on shape-based image database search using the technique of modal matching. Modal matching employs a deformable shape decomposition that allows users to select example objects and have the computer efficiently sort the set of objects based on the similarity of their shape. Shapes are compared in terms of the types of nonrigid deformations (differences) that relate them. The modal decomposition provides deformation "control knobs" for flexible matching and thus allows for selecting weighted subsets of shape parameters that are deemed significant for a particular category or context. We demonstrate the utility of this approach for shape comparison in 2-D image databases; however, the general formulation is applicable to signals of any dimensionality.

The Specialized Mappings Architecture

A probabilistic, nonlinear supervised learning model is proposed: the Specialized Mappings Architecture (SMA). The SMA employs a set of several forward mapping functions that are estimated automatically from training data. Each specialized function maps certain domains of the input space (e.g., image features) onto the output space (e.g., articulated body parameters). The SMA can model ambiguous, one-to-many mappings that may yield multiple valid output hypotheses. Once learned, the mapping functions generate a set of output hypotheses for a given input via a statistical inference procedure. The SMA inference procedure incorporates an inverse mapping or feedback function in evaluating the likelihood of each of the hypothesis. Possible feedback functions include computer graphics rendering routines that can generate images for given hypotheses. The SMA employs a variant of the Expectation-Maximization algorithm for simultaneous learning of the specialized domains along with the mapping functions, and approximate strategies for inference. The framework is demonstrated in a computer vision system that can estimate the articulated pose parameters of a human’s body or hands, given silhouettes from a single image. The accuracy and stability of the SMA are also tested using synthetic images of human bodies and hands, where ground truth is known.

StaXML: Static Typing of XML Document Fragments for Imperative Web Scripting Languages

We present a type system, StaXML, which employs the stacked type syntax to represent essential aspects of the potential roles of XML fragments to the structure of complete XML documents. The simplest application of this system is to enforce well-formedness upon the construction of XML documents without requiring the use of templates or balanced "gap plugging" operators; this allows it to be applied to programs written according to common imperative web scripting idioms, particularly the echoing of unbalanced XML fragments to an output buffer. The system can be extended to verify particular XML applications such as XHTML and identifying individual XML tags constructed from their lexical components. We also present StaXML for PHP, a prototype precompiler for the PHP4 scripting language which infers StaXML types for expressions without assistance from the programmer.

ImageRover: A Content-Based Image Browser for the World Wide Web

ImageRover is a search by image content navigation tool for the world wide web. To gather images expediently, the image collection subsystem utilizes a distributed fleet of WWW robots running on different computers. The image robots gather information about the images they find, computing the appropriate image decompositions and indices, and store this extracted information in vector form for searches based on image content. At search time, users can iteratively guide the search through the selection of relevant examples. Search performance is made efficient through the use of an approximate, optimized k-d tree algorithm. The system employs a novel relevance feedback algorithm that selects the distance metrics appropriate for a particular query.

Image Digestion and Relevance Feedback in the ImageRover WWW Search Engine

ImageRover is a search by image content navigation tool for the world wide web. The staggering size of the WWW dictates certain strategies and algorithms for image collection, digestion, indexing, and user interface. This paper describes two key components of the ImageRover strategy: image digestion and relevance feedback. Image digestion occurs during image collection; robots digest the images they find, computing image decompositions and indices, and storing this extracted information in vector form for searches based on image content. Relevance feedback occurs during index search; users can iteratively guide the search through the selection of relevant examples. ImageRover employs a novel relevance feedback algorithm to determine the weighted combination of image similarity metrics appropriate for a particular query. ImageRover is available and running on the web site.

Specialized Mappings Architecture with Applications to Vision-based Estimation of Articulated Body Pose

A fundamental task of vision systems is to infer the state of the world given some form of visual observations. From a computational perspective, this often involves facing an ill-posed problem; e.g., information is lost via projection of the 3D world into a 2D image. Solution of an ill-posed problem requires additional information, usually provided as a model of the underlying process. It is important that the model be both computationally feasible as well as theoretically well-founded. In this thesis, a probabilistic, nonlinear supervised computational learning model is proposed: the Specialized Mappings Architecture (SMA). The SMA framework is demonstrated in a computer vision system that can estimate the articulated pose parameters of a human body or human hands, given images obtained via one or more uncalibrated cameras. The SMA consists of several specialized forward mapping functions that are estimated automatically from training data, and a possibly known feedback function. Each specialized function maps certain domains of the input space (e.g., image features) onto the output space (e.g., articulated body parameters). A probabilistic model for the architecture is first formalized. Solutions to key algorithmic problems are then derived: simultaneous learning of the specialized domains along with the mapping functions, as well as performing inference given inputs and a feedback function. The SMA employs a variant of the Expectation-Maximization algorithm and approximate inference. The approach allows the use of alternative conditional independence assumptions for learning and inference, which are derived from a forward model and a feedback model. Experimental validation of the proposed approach is conducted in the task of estimating articulated body pose from image silhouettes. Accuracy and stability of the SMA framework is tested using artificial data sets, as well as synthetic and real video sequences of human bodies and hands.

Smooth Multirate Multicast Congestion Control

A significant impediment to deployment of multicast services is the daunting technical complexity of developing, testing and validating congestion control protocols fit for wide-area deployment. Protocols such as pgmcc and TFMCC have recently made considerable progress on the single rate case, i.e. where one dynamic reception rate is maintained for all receivers in the session. However, these protocols have limited applicability, since scaling to session sizes beyond tens of participants necessitates the use of multiple rate protocols. Unfortunately, while existing multiple rate protocols exhibit better scalability, they are both less mature than single rate protocols and suffer from high complexity. We propose a new approach to multiple rate congestion control that leverages proven single rate congestion control methods by orchestrating an ensemble of independently controlled single rate sessions. We describe SMCC, a new multiple rate equation-based congestion control algorithm for layered multicast sessions that employs TFMCC as the primary underlying control mechanism for each layer. SMCC combines the benefits of TFMCC (smooth rate control, equation-based TCP friendliness) with the scalability and flexibility of multiple rates to provide a sound multiple rate multicast congestion control policy.