VictorJuiz/thesis huggingface dataset:
Molecular logic of adult stem cell self-renewal and the commitment to differentiation in the Drosophila testis stem cell niche [electronic resource]

Adult stem cells both self-renew and give rise to differentiating progeny that maintain and repair tissues throughout an individual's lifetime. Adult stem cells reside in specialized microenvironments, or niches, that regulate stem cell behavior in vivo. The Drosophila testis contains a complex niche that maintains two adult stem cell populations, germline stem cells (GSCs) and somatic cyst stem cells (CySCs), which are directly anchored to a plug of post-mitotic support cells called the hub. A short-range, cytokine-like signal from the hub, the ligand Unpaired (Upd), activates the JAK-STAT pathway in adjacent GSCs and CySCs to promote stem cell maintenance. To map the regulatory circuitry downstream of Upd signaling from the hub, I identified genomic sites of STAT binding in GSCs and CySCs by performing chromatin immunoprecipitation with antibodies against activated STAT, followed by high throughput Solexa sequencing (ChIP-Seq). My analysis suggests that forked regulatory circuits lay downstream of activated STAT in GSCs and CySCs, with different tines containing target gene(s) that regulate unique aspects of stem cell identity and behavior, including sustained receptivity to niche signals, expression of transcriptional regulators required for stem cell fate, and cell-cell communication between germline and soma. Adult stem cell behavior is also influenced by cell-intrinsic factors, including transcription and chromatin remodeling factors, which enable stem cells to interpret and execute appropriate responses to niche signals. I discovered that the transcriptional regulator longitudinals lacking (lola) is required cell autonomously for GSC and CySC maintenance: stem cells homozygous mutant for lola detach from the hub and differentiate. In addition, I found that activity of lola is also required for proper execution of key developmental transitions during germ cell differentiation, including the timely switch from the transit amplification divisions to the spermatocyte growth and gene expression program, and subsequently for the meiosis and spermatid differentiation.

Keywords: Developmental Biology.
Advisor: Fuller Margaret
Baker Julie (Professor of genetics) advisor. Thesis advisor
Kingsley David M. (David Mark) advisor. Thesis advisor
Nusse Roel
Villeneuve Anne
Molecular mechanisms of the innate immune response to Francisella tularensis [electronic resource]

Francisella tularensis is a facultative intracellular pathogen that causes the disease tularemia. The ability of F. tularensis to escape phagosomal degradation and replicate in the macrophage cytosol is central to its pathogenesis. The macrophage responds to the presence of cytosolic F. tularensis with the production of type-I interferons (IFN) and subsequent activation of the inflammasome. We conducted a forward genetic screen of a F. novicida transposon library to identify mutants that resulted in an increased or decreased cytosolic response in macrophages. We identified 164 F. novicida mutants that lead to increased type-I IFN production and inflammasome activation in macrophages. We also identified 74 mutants that resulted in decreased type-I IFN and inflammasome responses in macrophages. Finally, we identified AIM2 as the host receptor responsible for inflammasome activation in response to cytosolic F. novicida. We showed that lysing cytosolic F. novicida leads to release of bacterial DNA that triggers type-IFN through a pathway involving the adaptor STING. STING-dependent type-I IFN production increases the expression of AIM2, which complexes with the bacterial DNA and initiates inflammasome activation. We further demonstrate that AIM2 is critical for innate immunity to F. novicida infection in vivo. Thus we identified a novel bacterial ligand and novel cytosolic sensing components that play a role in the host defense to bacterial infections.

Keywords: Microbiology and Immunology
Advisor: Monack Denise M. primary advisor. Thesis advisor
Amieva Manuel advisor. Thesis advisor
Falkow Stanley advisor. Thesis advisor
Nelson W. J. (W. James) advisor. Thesis advisor
Schneider David (David Samuel)
Molecular origins of mechanical properties in hybrid glasses [electronic resource]

Hybrid organic-inorganic glasses are materials wherein organic and inorganic chemical components are intermixed and covalently bound at the molecular scale. This class of materials has great potential to enable and enhance a range of new technologies given their unique properties. To date, hybrid glasses have been used in a diverse range of applications including protective coatings, adhesion promoting films, ultra-low-k dielectrics, and optical waveguides. The successful integration of hybrid glasses requires that they possess sufficient mechanical properties to withstand often harsh processing and operating conditions. This dissertation presents results from several investigations of how molecular structure controls elastic and fracture properties of hybrid glasses. Two major sol-gel derived hybrid glass systems are discussed. The first is oxycarbosilane (OCS) glasses processed from small organosilane precursors. The second system is ZrOx/epoxysilane hybrids. For the OCS glasses, the primary focus of this work was to develop the capability to generate accurate molecular models of these materials and to simulate their mechanical properties using molecular dynamics as well as a novel fracture model that uses the mathematics of graph theory to predict the 3-D cohesive fracture path at the atomic scale. Using these computational tools, the impact of network connectivity on elastic stiffness and cohesive fracture energy has been elucidated. Also, the exceptionally high stiffness of OCS materials processed from 1,3,5-benzene precursors predicted by computational modeling is discussed. For the ZrOx/epoxysilane materials, linear elastic fracture mechanics experiments were done to characterize the fracture resistance of these glasses under monotonic, static, and cyclic loading conditions. The effects of glass composition, substrate composition, and silane crosslinking on the critical fracture energy were investigated. Additionally, plasticity-driven cyclic mechanical fatigue was observed, providing the first evidence of the importance of fatigue phenomena to hybrid glasses.

Keywords: Materials Science and Engineering
Advisor: Dauskardt R. H. (Reinhold H.) primary advisor. Thesis advisor
Cai Wei
Dubois Geraud advisor. Thesis advisor
Molecular signatures of virome-host interactions [electronic resource]

Small RNAs that are 19-30 nucleotides in length use the genetic information encoded in their sequence to effect gene regulation in a sequence-directed manner. Infections with RNA viruses in plants, worms and flies generate short viral-derived RNAs ("vsRNAs") that map to the genome of the infecting virus. The regulated production of these vsRNAs and their engagement by the immune apparatus is essential for inhibiting viral growth, making vsRNAs important components of antiviral immunity in these organisms. RNA virus-derived vsRNA-mediated gene silencing is yet to be demonstrated in mammalian systems. We investigated diverse RNA virus-mammalian systems, and characterized changes in small RNA populations that occur during viral infection in animal cells using high-throughput sequencing. Due to the large number of samples to be analyzed, we designed DNA barcodes to 'tag' RNA samples from individual experiments, which facilitated sequencing in parallel from multiple samples. Our work demonstrated the generality of RNA virus-derived vsRNA production, and the ability of the cellular short RNA apparatus to engage these vsRNAs in worms during Flock House Virus replication, and in mammalian cells during infections with Hepatitis C, Polio, Dengue, Vesicular Stomatitis or West Nile virus. In addition to the appearance of vsRNAs during infection, we saw a number of specific changes in host-encoded small RNA (miRNA) profiles. For several infection models investigated in more detail, the RNAi and Interferon pathways modulated the abundance of vsRNAs. We found evidence for populations of vsRNAs that exist as duplexed small interfering RNAs ("siRNAs; " effectors of gene silencing) with zero to three nucleotide 3' overhangs. We also observed strand-selective loading of siRNAs onto Argonaute complexes, which are mediators of gene silencing. We quantitated the capacity of these HCVrep-derived vsRNAs to down-regulate target mRNAs in a sequence-specific manner in mammalian systems. We found that abundant HCVrep vsRNAs are not capable of mediating robust silencing (i.e. 2-fold or higher) of Luciferase reporters that have been engineered with vsRNA targets. Additionally, over-expression of siRNAs corresponding to five abundant vsRNAs failed to enhance silencing of Hepatitis C Virus mRNA. These results complement each other and suggest that in mammalian hosts, the virus may coexist with an abundant population of vsRNAs. Questions still remain as to whether robust gene silencing may be achieved by the cooperative action of abundant vsRNAs, or if abundant vsRNAs specifically inhibited from functioning in gene silencing, or alternatively, if they have novel roles in pathways distinct from gene silencing.

Keywords: Microbiology and Immunology
Advisor: Fire Andrew Zachary primary advisor. Thesis advisor
Glenn Jeffrey S.
Kay Mark Allan advisor. Thesis advisor
Kirkegaard Karla advisor. Thesis advisor
Singh Upinder (Physician) advisor. Thesis advisor
Monolingual and bilingual children's integration of multiple cues to understand a speaker's referential intent [electronic resource] : the role of experience in cognitive development

Children growing up in a dual-language environment have to constantly monitor the dynamic communicative context to determine what the speaker is trying to say and how to respond appropriately. Such self-generated efforts to monitor speakers' communicative needs may heighten children's sensitivity to and allow them to make better use of communicative cues to figure out a speaker's referential intent. Chapter 1 of this paper reviews the current models of bilingualism and literature on the impact of growing up bilingual, including benefits to the cognitive and communicative development of children. Chapter 2 presents a series of studies to examine how the experience of growing up bilingual may foster children's ability to integrate multiple cues to understand a speaker's referential intent, and how the experience of a communication breakdown of a bilingual nature may increase children's sensitivity to communicative cues. Overall, results provide evidence that growing up in a bilingual environment facilitates a more sophisticated understanding of the demands in a communicative context and support the hypothesis that children's self-generated efforts to cope with communicative challenges heighten their sensitivity to a speaker's communicative intent and foster their cognitive and linguistic development.

Keywords: Psychology
Advisor: Markman Ellen M.
Boroditsky Lera advisor. Thesis advisor
Dweck Carol S.
Monte Carlo simulation of particle production and decay at high-energy colliders [electronic resource]

Detecting and understanding new physics at the LHC and other future colliders depends on having an understanding of what kinds of signals to look for above the Standard Model background. Event generators are used to simulate the physics events we can expect to see at these colliders and facilitate the search for and analysis of interesting signals. In this thesis we discuss the pandora event generator and its use for generating collider events with Beyond the Standard Model particles and their decays. First we will describe the physics fundamental to event generators, the particular philosophy behind the pandora generator, and how it compares to other available tools. Second, we will discuss how that particular philosophy was implemented and how the implementation facilitates incorporating new BSM physics. Finally we will discuss several physics results generated using pandora, displaying its various features.

Keywords: Physics
Advisor: Peskin Michael Edward
Hewett JoAnne L. advisor. Thesis advisor
Kachru Shamit
Multiple-rank updates to matrix factorizations for nonlinear analysis and circuit design [electronic resource]

For the numerical solution of ODE/PDEs that describe the basic laws of science, such as Kirchhoff's laws in circuit analysis, or nonlinear deformation equations in structural analysis, a series of linear equations Ax=b are generated to represent the basic laws. The size of A could reach 10 billion in full-chip verification, or 1 billion in structure-foundation seismic simulation. The traditional method is to solve these linear equations independently, which leads to a computational bottleneck when we simulate large and complicated objects because more than 95 percent of the simulation time lies in solving the equations. This thesis addresses the computational bottleneck by modifying the matrix A's factorization at each simulation step based on the similarities between two consecutive linear systems. To achieve this aim, we define the similarities as an initial matrix A with multiple-rank corrections. Then we design algorithms to solve the linear systems based on updating concepts. The basic algorithm is a rank-1 update of the factors of an unsymmetric matrix. To maintain stability, new algorithms are designed to implement partial or full pivoting strategies for the update procedure. To improve performance and overcome parallelization difficulties during traditional factorization, a pipeline is designed to do multiple-rank updates of the matrix factors. We prove two theorems for this parallel computing. One states that the multiple-rank update sequences are independent. The other, called the Base-camp theorem, describes a multiple-rank merge rule to reduce the computing effort. A divide-and-conquer algorithm for sparse matrix factorization is also described. Finally, we apply the multiple-rank modification of matrix factors to nonlinear analysis in structural engineering and functionality verification in circuit design. The same process can be applied in other time-domain problems and nonlinear systems, including fluid dynamics, aerospace, chemical processing, structure analysis, graphics rendering, MEMS, seismic, biotech, and electromagnetic field analyses.

Advisor: Saunders Michael A. primary advisor. Thesis advisor
Liu Zhihong (Computational engineer)
Murray Walter advisor. Thesis advisor
Multiscale distributed estimation with applications to GPS augmentation and network spectra [electronic resource]

Distributed estimation uses a network of sensors to measure a set of variables. The computation tasks required for finding the optimal estimate can be divided among the sensor nodes in a way that can be implemented as an iterative process using nodes with little computational power. Most algorithms for distributed estimation work for small networks, but convergence rates decrease with network size, making them impractical for use in large networks. We present a consensus algorithm with a convergence rate that scales logarithmically with network size by arranging nodes in a multigrid network structure. The algorithm can adapt to changes in the network structure and allows for selection of several parameters, representing a trade-off between performance and robustness of the network. We also describe how the algorithm is adapted to account for time-varying measurements and measurement weights. We present two applications of these methods. Our first application is an algorithm that allows us to determine the spectral properties of a state transition matrix on the network. Since the convergence rate of a consensus algorithm is related to the spectral properties of the state transition matrix, we can use this information to evaluate the effects of changes to the network structure. Our second application is a distributed GPS augmentation system. Traditional GPS augmentation systems use reference receivers to find a set of error correction values, which is broadcast to surrounding mobile receivers. Our distributed augmentation system uses only mobile receivers with unknown locations, which are able to obtain a set of correction values by sharing and processing data in a distributed network. The resulting method can be used to improve GPS point positioning accuracy in areas where fixed augmentation systems are not available.

Keywords: Aeronautics and Astronautics
Advisor: Lall Sanjay primary advisor. Thesis advisor
West Matthew
Enge Per advisor. Thesis advisor
Nano C-apertures applied to near-field inspection and data storage [electronic resource]

The restriction of optical spot sizes to the diffraction limit of ~lambda/2 is a long standing problem in optical imaging and optical data storage. As the length scales of interest to scientists and engineers have decreased, the need for a way to efficiently focus light to spot sizes of < lambda/10 has become more pressing. Near-field optical techniques are the only solution to optical probing at the deeply sub-wavelength scale, but the existing methods of solid immersion lenses, sharp probe tips and sub-wavelength apertures (NSOM) are all hampered by significant deficiencies. The nano C-aperture is a superior near-field optical source and FDTD simulations have shown that it is able to produce very small and intense near-field optical spots. Unfortunately, conventional fabrication methods are incapable of producing C-apertures that fully realize the high, absolute field intensities promised by simulations. Using a new silicon nitride membrane based fabrication method, the performance of the C-aperture can be greatly enhanced both in the near and far-field. In this dissertation, I present data demonstrating the improvements in transmitted power and near-field spot size offered by this new fabrication technique and I apply the improved apertures to near-field inspection and optical data storage. I show that the near-field spot can be used for optical imaging at a resolution of lambda/10 with an optical intensity ~10x higher than conventionally-fabricated C-apertures. Finally, I show that the improved C-aperture can be used to record and read data bits in a phase change recording medium (Ge2Sb2Te5) with minimum bit sizes of 53.5x50.2 nm or ~lambda/20.

Keywords: Applied Physics
Advisor: Hesselink Lambertus primary advisor. Thesis advisor
Miller D. A. B. advisor. Thesis advisor
Pease R. (R. Fabian W.) advisor. Thesis advisor
Nanoelectronics [electronic resource] : technology assessment and projection at the device, circuit, and system level

Nowadays, physical gate length can no longer be effectively scaled down and traditional boosters (e.g., strain, high-k/metal gate) are having diminishing return. Continued progress in nanoelectronics necessitates a holistic view across the boundaries of device, circuit and system. The best devices are those that are optimized for the circuits and systems of the target application. Device design and engineering must aim at improvement at circuit and system level, while the new applications in various areas, such as life-science, are enabled by emerging technology. In this dissertation, the design space is explored for future Si CMOS technology, and several promising technologies in the post-Si era. Compact models of transport properties and capacitive components of different device structures have been developed to facilitate circuit-level analysis and system-level optimization. Possible ways of extending technology roadmap are proposed. We propose scenarios of selective device structure scaling that will enable Si CMOS technology scaling for several generations beyond the currently perceived limits. Beyond Si CMOS scaling, carbon nanotube field effect transistors (CNFETs) are optimized and projected to achieve 5x chip-level speed up over PDSOI with the same power constraints at 11 nm technology node for a high-performance four-core processor with 1.5M logic gates and 5MB SRAM per core. A new simple device technology assessment methodology based on energy-delay optimization is also introduced and applied on emerging devices including CNFETs, III-V field effect transistors (IIIV), and tunneling field effect transistors (TFET). In conclusion, this thesis addresses the significance of a holistic view across the traditional boundaries of device, circuit, and system in technology assessment and projection. Guided by this concept, we chart a new path for Si CMOS technology scaling for future technology generations. We also accomplish for the first time chip-level performance assessment and optimization of new emerging transistors such as CNFETs. This establishes a new benchmark and design methodology for emerging nanoelectronics.

Keywords: Electrical Engineering
Advisor: Wong Hon-Sum Philip
Mitra Subhasish advisor. Thesis advisor
Saraswat Krishna advisor. Thesis advisor
Network analysis and drug target identification in mast cells [electronic resource]

Target identification is both a critical and difficult step in the drug discovery process. A novel approach is presented here that utilizes flow cytometry to: 1) identify small molecule signaling network probes, and 2) characterize the diverse network activation states they induce. Signaling events across the network are compared to functional responses to determine the way in which each signaling node influences a given function. Nodes that accurately predict cellular functions that drive disease are promising drug targets. The approach was applied to mast cells to determine which signaling molecules best predicted the degranulation, eicosanoid release, and cytokine secretion induced by stimulation of the cells with IgE and specific antigen crosslinking. Erk and Akt phosphorylation best predicted degranulation; Erk and cJun phosphorylation best predicted eicosanoid release; and Akt phosphorylation alone best predicted cytokine secretion. The results confirmed several known aspects of mast cell IgE-dependent signaling and revealed unknown associations to be tested in future work -- notably, that the cJun pathway plays a role in eicosanoid production and that the Akt pathway is a critical integration point for transcription of most or all cytokine genes. Overall, the results suggest that Erk and Akt are the most promising targets in the IgE signaling network for development of mast cell stabilizing drugs.

Keywords: Immunology.
Advisor: Nolan Garry P. primary advisor. Thesis advisor
Chen James Kenneth advisor. Thesis advisor
Davis Mark M. advisor. Thesis advisor
Galli Stephen J. advisor. Thesis advisor