VictorJuiz/thesis huggingface dataset:
Molecular Characterization of the Interaction between Bcl-2 and Nur77/Nor-1 in Apoptosis

As an essential safeguard against autoimmunity, apoptosis during negative selection of self-reactive T cell precursors is important in establishing a self-tolerant T cell repertoire capable of responding to a large array of foreign antigens. The fate of a thymocyte is imposed by signals through the T cell receptor (TCR). During T cell development, thymocytes expressing TCRs that strongly react to self-antigens in the thymus trigger apoptosis and die. The Nur77 family of orphan nuclear hormone receptors and the Bcl-2 family of proteins are important molecules implicated in thymocyte apoptosis and clonal deletion. Strong TCR signals induce the expression and translocation of Nur77 and Nor-1 from the nucleus to the mitochondria, where they bind Bcl-2 and expose Bcl-2’s pro-apoptotic, killer BH3 domain. Through extensive Bcl-2 mutagenesis and functional assays, we identify residues within Bcl-2 that are essential for Nur77/Nor-1 interaction. We find that the Bcl-2 mutants that interfere with this interaction do not affect normal Bcl-2 anti-apoptotic function, but lose the ability to mediate Nur77/Nor-1-initiated apoptosis. This study refines the molecular details of this interaction and may assist in generating a novel tool to study the significance of this interaction in vivo. The importance of the Bcl-2 BH3 domain was revealed in Bcl-2 BH3 transgenic mice (BH3* Tg) where the BH3 domain is mutated. Unlike mice with a T cell-specific transgenic expression of wild-type Bcl-2, BH3* Tg mice exhibited accelerated morbidity from multi-organ autoimmunity. To further understand what might cause autoimmunity in these mice, we identified a provisional ubiquitous autoantigen found in the antisera of BH3* Tg mice. This data provides the groundwork to further study the potential cause of autoimmune syndrome in these mice. The increase of an autoreactive T cell repertoire in BH3* Tg mice may reject tumor better since self-antigens are largely shared by tumors. However, we found that the presence of an increased autoreactive T cell repertoire in BH3* Tg mice exacerbates tumor growth and morbidity. In sum, this work advances our understanding of molecular mechanisms involved in T cell negative selection and offers insights into the etiology in autoimmunity pathology and potential use for cancer immunotherapy.

Advisor: Winoto, Astar
Poetic Versus: Conflicting Great War Poems

This dissertation is a close look at poems written during the Great War by Thomas Hardy, Edward Thomas, and Wilfred Owen. I describe how each deploys poetry’s formal resources to engage the affective, cognitive, spiritual, and political problems the war produces for them. I argue that strategies of poetic doubling allow them to address—if not quite assuage—the effects of the war that trouble them the most. Each poem manifests this doubling in different ways, but the tactic of doubling is pervasive. Ultimately, I argue that this doubling is equally an effect of the war’s incessant production of antagonistic cultural forms, and of lyric poetry’s fundamental ability to accommodate internal opposition at the formal level. The intrinsic ambivalence of poetic form makes it a particularly effective discourse for examining war’s social and political contradictions./nThis unifying theme of formal doubling or what I call the “poetic versus”—double timeframes in Hardy, double identities and locations in Thomas, and two or more opposing verbal registers in Owen—is a careful instantiation of Isobel Armstrong’s influential figure of the “double poem.” I track examples of how poems formally enact the kind of doubleness Armstrong describes—how they enact a second-order commentary on their own primary expression. Doubling is a broad but apt name for the strategies by which the war’s disturbances and antagonisms are transferred between the poem’s double levels of engagement, whether conceived as formal/social (Raymond Williams), literary/political (Caroline Levine) or expressive/epistemological (Isobel Armstrong)./nThe prominent forms of doubling I identify line up with tenets of liberal political thought threatened by the war: Hardy’s trouble with time is tied to a belief in rational human progress that the war renders increasingly difficult to maintain. Thomas’s dual identities, in light of the economic forces that ultimately forced him to abandon writing for a soldier’s salary, are traceable to a crisis of alienation underlying liberalism’s basis in the individual. Owen’s project of incorporating voices of inherited cultural tradition and authority, only to expose them as the very origins of the war’s depredations is a critique of liberalism cast as a personal betrayal. Drawing on critical work by William Empson and Paul Fussell, I identify a complex form of irony as the crucial intellectual and affective stance which poetic doubling enables, a stance that becomes an increasingly important cultural survival strategy as the war persists.

Advisor: Puckett, Kent
Interrogation of Neural Circuits of the Basal Forebrain and Midbrain for Sleep-Wake Regulation

In mammals, sleep is comprised of two distinct stages, rapid eye movement (REM) and non-REM (NREM) sleep. The regulation of the sleep-wake cycle involves many brains regions that influence the probability of each state. Since many brain regions contain a mixed population of wake-promoting and sleep-promoting neurons, it remains a challenge to dissect and interrogate the neural circuits of sleep-wake regulation./nIn Chapter 2, I describe the mapping of neural circuits of the basal forebrain (BF) known to regulate wake and NREM sleep. The BF contains a spatially intermingled diverse population of neurons that plays key roles in multiple brain functions, including sleep-wake regulation, attention, and learning/memory. For sleep-wake regulation, the cholinergic, glutamatergic, and parvalbumin-expressing (PV) GABAergic neurons have been shown to promote wakefulness, whereas the somatostatin-expressing (SOM) GABAergic neurons promote NREM sleep. To better understand the functional specialization of these cell types, we performed whole-brain mapping of both inputs and outputs of these four BF cell types in the mouse brain. Using rabies virus-mediated monosynaptic retrograde tracing to label the inputs and adeno-associated virus to trace axonal projections, we identified numerous brain areas connected to the BF. The inputs to different cell types were qualitatively similar, but the output projections showed marked differences. The connections to glutamatergic and SOM+ neurons were strongly reciprocal, while those to cholinergic and PV+ neurons were more unidirectional. These results reveal the long-range wiring diagram of the BF circuit with highly convergent inputs and divergent outputs and point to both functional commonality and specialization of different BF cell types./nIn Chapter 3, I describe the interrogation of the midbrain ventrolateral periaqueductal gray (vlPAG), known to be important for gating REM sleep. We demonstrated that activating vlPAG GABAergic neurons in mice suppressed the initiation and maintenance of REM sleep while consolidating NREM sleep, partly through their projection to the dorsolateral pons. Cell-type-specific recording and calcium imaging showed that most vlPAG GABAergic neurons are strongly suppressed at REM sleep onset and activated at its termination. In addition to the rapid changes at brain state transitions, their activity decreases gradually between REM sleep and is reset by each REM episode in a duration-dependent manner, mirroring the accumulation and dissipation of REM sleep pressure. Thus, vlPAG GABAergic neurons powerfully gate REM sleep, and their firing rate modulation may contribute to the ultradian rhythm of REM/NREM alternation.

Advisor: Dan, Yang
Integrating Technology into Literacy Instruction for Students with Disabilities: Perspectives of Teachers and Students

Abstract/nIntegrating Technology into Literacy Instruction for Students with Disabilities:/nPerspectives of Teachers and Students/nby/nCatherine Lipson/nDoctor of Philosophy in Special Education/nUniversity of California, Berkeley and San Francisco State University/nProfessor P. David Pearson, Chair/nAs students with disabilities increase their participation in the general education curriculum, special education service providers must ensure equitable access to technology based learning resources (Edyburn, 2009; Leeman, 2013; Ottenbreit-Leftwich et al., 2015). While there are many opportunities to make content accessible to students through technology, the proliferation of choices in the technology marketplace makes it more difficult to select the appropriate resources. Many service providers lack experience and expertise with integrating technology into literacy instruction for secondary and postsecondary students with disabilities (Holmes & Silvestri, 2012; Burgos, 2015). This study used a three-tiered cascade sampling method to identify teachers who have demonstrated expertise with technology integration and literacy instruction. The purposes of the study included identifying, analyzing, and interpreting best practices for teachers and other professionals who provide technology services to students with disabilities. Interviews with teachers and observations of their classroom practices revealed how they adapted instruction and included accommodations to improve accessibility, as well as their beliefs and expectations about using technology in the classroom./nFindings from teacher interviews and classroom observations showed substantial differences between the secondary and postsecondary environments. Secondary teachers reported a lack of technology resources in afterschool or tutoring programs outside the classroom to help their students with homework assignments. In contrast, community college instructors described opportunities for students to get support from academic coaches or tutors in assistive technology labs or learning centers. These results suggested that teachers’ beliefs and expectations about student learning characteristics and the need for individual assistance were important factors underlying the differences seen in technology use in their classrooms./nAmong the postsecondary students who agreed to be interviewed, two students held positive views about alternative formats for reading, writing, or note-taking while one student was slightly positive to neutral about the benefits of recorded notes. Findings suggested the need for an education plan that stretches across multiple semesters or school years and specifies technology supports for secondary and postsecondary students, along with any training and support needed. Future research could trace the short-term and long-term effects of the shift away from print textbooks to electronic texts to determine how digital media influence student learning outcomes.

Advisor: Pearson, P. D.
Increasing Freeway Capacity by Efficiently Timing its Nearby Arterial Traffic Signals

On-ramp metering at freeway bottlenecks is an effective method of reducing a freeway system’s delay because empirical studies have previously shown that metering can prevent capacity drop, or reduction of outflow as a result of queue formation. However, arterial traffic signals that facilitate access to freeway on-ramps operate independent of the traffic conditions on the freeway on-ramp. Consequently, the traffic signals employ long signal cycle lengths and thus long green durations to maximize capacity at the arterial signalized intersections, which result in long platoons of freeway-bound traffic advancing toward the on-ramps. This often causes queue spillback on the freeway on-ramps and the surface street network. Queue override, a function that terminates or significantly relaxes the on-ramp metering rate whenever a sensor placed at the entrance of the on-ramp detects a potential queue spillover of the on-ramp vehicles on the adjacent surface streets, has become a widely accepted method of resolving queue spillback on the freeway on-ramps and nearby surface streets. Unfortunately, queue override releases the queue into the freeway and negates the benefit of ramp metering during the peak hours with recurrent freeway congestion. Video data collected downstream of freeway/on-ramp merge in San Jose, California show that the bottleneck discharge flow diminishes when queue override is activated for a sustained period of time. Observations over a two-week period suggest that queue override reduces the bottleneck discharge flow by an average of 10%./nRecently, there has been significant interest in integrated corridor management (ICM) of facilities comprised of freeways and adjacent arterial streets. Significant benefits can be realized by preventing queue override and effectively storing the queued vehicles on the nearby arterial surface streets if the arterial traffic signals can account for traffic conditions on freeway on-ramps and avoid sending long platoons to the freeway on-ramp. A signal control strategy was developed and evaluated in this study. The algorithm takes available on-ramp storage and freeway ramp metering rate into account and dynamically reduces the cycle length and adjusts the green durations to prevent on-ramp queue spillback and mitigate unnecessary delay in the conflicting arterial directions. The proposed algorithm was tested through simulation and the results show that the proposed strategy reduces the freeway and system-wide delay even under fluctuations in traffic demand, at a modest penalty on the on-ramp bound traffic.

Advisor: Skabardonis, Alexander
A Second-Order Møller–Plesset Perturbation Theory Energy Decomposition Analysis for Intermolecular Interactions: Design, Implementation, and Application

This thesis is concerned with the development an analysis for decomposing the binding energy of second-order Møller–Plesset perturbation theory into physically meaningful components. This can be defined as an extension to the previous work on an absolutely localized molecular orbitals based EDA for Hartree–Fock. The decomposition of the correlation energy proceeds though physically motivated constrained intermediate wave functions and corrects the HF description of frozen interaction, polarization, and charge transfer, while adding a description of dispersion that is only possible at the correlated level. This method is implemented efficiently and the performance of the implementation is tested. The EDA is then applied to systems of chemical interest to help resolve questions related to intermolecular interactions.

Advisor: Head-Gordon, Martin P
A Hypothalamic Switch for REM and Non-REM Sleep

Rapid eye movement (REM) and non-REM (NREM) sleep are controlled by specific neuronal circuits. In this thesis, I show that galanin-expressing GABAergic neurons in the dorsomedial hypothalamus (DMH) comprise separate subpopulations with opposing effects on REM versus NREM sleep. Microendoscopic calcium imaging revealed diverse sleep-wake activity of DMH GABAergic neurons, but the galanin-expressing subset falls into two distinct groups, either selectively activated (REM-on) or suppressed (REM-off) during REM sleep. Retrogradely labeled, preoptic area (POA)-projecting galaninergic neurons are REM-off, whereas the raphe pallidus (RPA)-projecting neurons are primarily REM-on. Bidirectional optogenetic manipulations showed that the POA projectors promote NREM sleep and suppress REM sleep, while the RPA projectors have the opposite effects. Thus, REM/NREM switch is regulated antagonistically by galaninergic neurons with intermingled cell bodies but distinct axon projections.

Advisor: Dan, Yang
Developing experimental and computational tools for sequence-census assays

Genomic data has revolutionized biology. The related development of high-throughput DNA sequencers has had a major impact on this, as the DNA sequencing platforms are widely adaptable to a number of assays that measure aspects of biology that are increasingly unrelated to the problem for which they were built: to understand the content of a genome. Such experiments, termed sequence-census assays, leverage the power of these machines to yield high throughput digital information about a molecular sample. Although there is large variability within these assays, there are main themes to the structure of these experiments: they encode molecular information into a sequencable format by performing a limited set of molecular biology operations on a pool of nucleic acids, then they read out this information by sequencing, and finally decode the sequenced message computationally. Importantly, during this process the computational decoding and experimental encoding of this information are coupled, and as such both ’wet’ and ’dry’ parts of an assay must be designed and treated together. In this thesis I explore these aspects of sequence-census assays, and their application to biologically unrelated, but computationally similar problems, ranging from CRISPR biology to single-cell sequencing.

Advisor: Doudna, Jennifer A
Pachter, Lior
Socialization Circles – Using Site-Based Teacher Leaders to Provide Meaningful Socialization Support to New Staff in Urban Schools

Overall, the evidence consistently paints a bleak picture of the socializing experiences new teachers typically face when entering into urban schools, resulting in higher levels of turnover and lower levels of professional efficacy for teachers new to their urban school settings. The study seeks to improve the socialization experience of new teachers at a large urban high school in Southern California, where norms of isolation, lack of trust, and problematic induction experiences prevail. Consequently, the school has struggled to retain new staff and lift the academic performance of students. The study utilizes a design development methodology that draws on teacher socialization research to inform the design of an intervention that can ameliorate the contextual challenges new teachers are facing at the school. Specifically, the intervention seeks to broker relationships of trust, develop conversational norms focused on instructional practice, and encourage more frequent informal interactions amongst new and experienced teachers. To accomplish this, the intervention engages new and experienced teachers together in bi-weekly instructional support sessions over the course of the first semester of school that use a consultancy model to focus conversations on classroom-based problems of practice. Experienced teachers also participate in a series of reorientation sessions designed to familiarize experienced teachers with the conceptual definitions of supportive professional cultures and high quality informal interactions, and to support participants as they attempt to engage new staff in more informal interactions. While these intervention efforts fell short in some respect, they also registered measurable impact in important ways, including the willingness of new teachers to seek out additional help and engage in conversations about specific challenges they are facing in the classroom.

Advisor: Mintrop, Heinrich
Generation, Characterization, and Migration Behavior of Vesicle Suspensions

This dissertation is an attempt to address open questions in the area of suspension migration behaviors that have been observed. Different flow regimes and their corresponding migration behaviors are introduced, and the lack of experiments investigating the collective migration behavior of deformable particle or vesicle suspensions is discussed. One of the reasons for this gap in the literature is the absence of readily available, well-controlled vesicle suspensions (or another model deformable particle suspension). Vesicles are attractive to study because their dynamic behavior in flow is similar to that observed for cells of interest (e.g. red blood cells), but most vesicle generation methods produce very polydisperse vesicle suspensions – or suspensions with a broad distribution of vesicle diameters. The development of a protocol for reduced-polydispersity vesicle suspensions involves a parametric study of electroformation as a vesicle generation method, as well as the application of microfluidic separation technologies, originally developed for suspensions of particles and cells. Because the resulting vesicle suspensions still exhibit some polydispersity, migration experiments are performed with a bidisperse suspension of rigid spherical particles to gain insight into the effect of polydispersity on migration behavior. Initial results indicate that even in dilute conditions, particles in mixed suspensions exert some influence over each other. Differences are observed when comparing migration lengths of particles in bidisperse suspensions to migration lengths of particles in monodisperse suspensions. Potential next steps and challenges to conducting migration experiments with vesicle suspensions are discussed.

Advisor: Muller, Susan J
The Desired Unsung: Black Middle-Class Men and Intimate Relationships

Popular discourses about the crises of Black family, marriage, and economic stability are refracted through the failure of low-income Black men. But, the academic discussion is also tinged by the “taint of the ghetto,” in which sociologists have tended to analyze the diverse experiences of Black relationships through a reductionist frame based on poverty and family disorganization. Black middle-class (BMC) men also carry the weight of these class-specific narratives (e.g., the absentee father, philanderer, drug dealer, or gang member)—not just because there is a dearth of knowledge about BMC heterosexual relationships but because everyone else—from single mothers, never married women, social commentators, and pundits—are speaking for Black men, except themselves./nBased on in-depth interviews, this dissertation seeks to enrich the debate surrounding Black relationships by including the perspectives of BMC men. It asks one overarching question that is often debated, yet never directly asked of the BMC men in question: How do heterosexual BMC men perceive and negotiate their relationships against the backdrop of dominant narratives that foreground their alleged failure? I find that within-class differences, specifically, the trajectory of BMC men’s social mobility patterns, timing of exposure to predominately white social environments, and racialized dating experiences are the three factors necessary to understand how BMC men experience intimate relationships.

Advisor: Ray, Raka