VictorJuiz/thesis huggingface dataset:
Synaptic Plasticity Induced Through CP-AMPARs is Dependent on the ERK/MAPK Signalling Cascade
Keywords: Synaptic plasticity
AMPA receptors
Calcium signalling
ERK/MAPK
LTP
CaMKII
GluR2
PI3K
Ras
L-LTP
protein synthesis
hippocampus
CA1
memory
ischemia
addiction
seizure
PAK1
ROCK2
calcium pemeable AMPA receptors
NMDA receptors
electrophysiology
knockout mice
Western Blot

Recent literature has shown that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors lacking the GluR2 subunit (thus calcium permeable) are widely expressed in the CNS, especially in interneurons and glia, where they contribute to synaptic transmission and plasticity. Studies have also indicated that calcium permeable AMPARs (CP-AMPARs) are expressed and participate in synaptic regulation in principal neurons, including hippocampal pyramidal neurons. Furthermore, CP-AMPARs and their resultant calcium influx are implicated in various pathophysiological conditions such as ischemia and seizures. However, the synaptic events activated by calcium influx through CP-AMPARs remain unknown. I took advantage of genetically altered mice without (GluR2-/-) or with reduced GluR2 (GluR2+/-), thus allowing the expression and detailed analysis of synaptic CP-AMPARs in hippocampal pyramidal neurons. Utilizing electrophysiological techniques, I demonstrated that these receptors were capable of inducing numerous forms of long-term potentiation (referred to as CP-AMPAR-dependent LTP) through a number of different induction protocols, including high-frequency stimulation (HFS) and theta-burst stimulation (TBS). This included a previously undemonstrated form of protein-synthesis dependent late-LTP (L-LTP) at CA1 synapses that is NMDA-receptor (NMDAR) independent. This form of plasticity was completely blocked by the selective CP-AMPAR inhibitor IEM-1460. Surprisingly, calcium/calmodulin-dependent kinase II (CaMKII), the key protein kinase that is indispensable for NMDAR-dependent LTP at CA1 synapses appeared to be not required for the induction of CP-AMPAR-dependent LTP due to the lack of effect of two separate pharmacological inhibitors (KN-62 and staurosporine) on this form of potentiation. Both KN-62 and staurosporine strongly inhibited NMDAR dependent LTP in control studies. In contrast, inhibitors for the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) cascade (PD98059 and U0126) significantly attenuated this CP-AMPAR-dependent LTP. Additional studies with knockout mice revealed that the ERK/MAPK signalling cascade is likely acting through p-21 activated kinase 1 (or PAK1, a Rho-GTPase associated kinase) dependent mechanisms. These results suggest that distinct synaptic signalling underlies GluR2-lacking CP-AMPAR-dependent LTP, and reinforces the recent notions that CP-AMPARs are important facilitators of synaptic plasticity in the brain.
The Aging Workforce: Addressing its Challenges Through Development of a Dignified Lives Approach to Equality
Keywords: Law
Labour Law
Employment Law
Labour Policy
Discrimination Law
aging workforce
senior workers
accommodation
mandatory retirement
age discrimination
theories of equality
equality sssessment

Against the background of the global demographic shift towards an aging workforce and its impacts on the labour market and the economy in industrialized societies, this dissertation pinpoints six salient challenges for future litigation and policy-making in the area of labour and employment discrimination law. These include the global tendency towards abolishing mandatory retirement and increasing the eligibility age for pension benefits; legislative age-based distinctions; cost as a justification for age discrimination; performance appraisals of senior workers; and the duty to accommodate senior workers. At the core of each challenge lies a normative question regarding our conception of senior workers’ right to age equality, its importance and relative weight compared with other rights and interests. The aim of this dissertation is therefore to critically review the current understanding of this right and its moral and economic underpinning. Most notably, the dissertation contends that the prevailing conception of equality assessment (the Complete Lives Approach to equality), according to which equality should be assessed based on a comparison of the total share of resources obtained by individuals over a lifetime, has substantial implications for age discrimination discourse. As it uncovers the numerous difficulties with the complete lives approach, the dissertation develops an alternative: the Dignified Lives Approach to equality, according to which an individual should be treated with equal concern and respect, at any particular time and regardless of any comparison. The dissertation then articulates five essential principles founded in Dworkin’s notion of equal concern and respect: the principle of individual assessment, the principle of equal influence, the principle of sufficiency, the principle of social inclusion, and the principle of autonomy. When one of these principles is not respected at any particular time, a wrong is done, and the right to equality is violated. Next, the dissertation elucidates when and why unequal treatment of senior workers based on age does not respect each of these five principles and therefore constitutes unjust age discrimination. It demonstrates that senior workers’ right to age equality is a fundamental human right. Finally, it examines the above-mentioned challenges through the lens of the new Dignified Lives approach.
Taking a Risk: Does Human Capital Investment Pay Off for Educationally Disadvantaged Adults?
Keywords: adult education
labour markets
returns to education
participation

Although human capital investment is often proposed as a solution to improve the labour market prospects of individuals who reach adulthood without obtaining a post-secondary credential, little is known about whether skills upgrading actually pays off. Using three national cross-sectional surveys on adult education as well as longitudinal data from the Panel Survey of Income Dynamics (1992-2005), I analyze how returning to school affects the earnings trajectories of men and women who enter the labour force with low levels of initial education. There are two major findings related to the earnings and advancement question. First, although both Canadian and American adults with low levels of initial education are significantly less likely than their more educated counterparts to participate in education and training, when they do participate, they are more likely to report it helped them increase their earnings. Second, these perceived gains are matched by substantial gains in actual earning growth. While the opportunity cost of returning to school is quite high – returnees experience a sharp drop in annual earnings during the years while they are in school – for both women and men, this investment yields a significant increase in earnings in the post schooling period. In addition, I address the question of why – if the earnings gains are so substantial – do so few less educated adults return to school? There are three key findings related to the participation question. First, even after accounting for a rich set of covariates, the effects of family of origin socio-economic status on educational attainment persist over the life course. Second, despite these enduring effects, current family and labour market dynamics matter as well. Consistent with the human capital model, I find evidence that, educationally disadvantaged individuals return to school to improve their labour market prospects. Taken together these results demonstrate that at least for some educationally disadvantaged adults, human capital investment is an effective strategy for labour market advancement. This conclusion challenges the standard ‘cumulative disadvantage’ view of adult education as simply another mechanism that serves to reproduce inequality.
L2 Learners’ Difficulties in the Interpretation of the Spanish Subjunctive: L1 Influence and Misanalysis of the Input
Keywords: L2 Acquisition
Spanish Subjunctive

This study examines L2 learners’ difficulties in the acquisition of the Spanish subjunctive. In particular, it investigates the interpretations English-speaking L2 learners of Spanish assign to the subjunctive in temporal, concessive, and conditional clauses, where mood choice involves the interaction of morpho-syntactic, semantic, and pragmatic knowledge. In contrast to previous research that has given little attention to the difficulties L2 learners experience, this study hypothesizes they might be attributed to “input traps” resulting from L1 transfer of syntactic and semantic properties of the subjunctive adjuncts and misanalysis of the input due to the lack of integration of different types of information. This study tests this claim by comparing the grammars of English-speaking L2 learners of Spanish with those of native Spanish speakers. If L2 learners share similar patterns with L1 speakers in contexts where both languages behave similarly, and exhibit different patterns from L1 speakers in contexts where both languages behave differently, difficulties should be attributed to L1 influence on the L2. On the other hand, if L2 learners exhibit different patterns from L1 speakers in contexts where semantic or pragmatic features determine the use of the subjunctive, difficulties should be attributed to failures in form-meaning mappings. Data collection involved a Preference Task with three possible options: a sentence with the indicative, with the subjunctive, or no preference. Subjects were asked to select which of the three choices they preferred according to the context presented in the story. Twenty advanced English-speaking L2 learners of Spanish and twenty native speakers from different Spanish-speaking countries, who served as the control group, took part in this study. Results indicate that subjunctive adjuncts present difficulties in L2 acquisition even for advanced L2 learners. Although they exhibit sensitivity to certain subjunctive features and contextual meanings, data reveal that convergence and non-convergence were primarily determined by L1 influence on L2. Crucially, those features absent from the L1 give rise to greater efforts and difficulties in L2 form-meaning mappings of mood selection.
A Perturbation-inspired Method of Generating Exact Solutions in General Relativity
Keywords: General Relativity
Exact solution
Cosmology
Perturbation
Astrophysics
Relativity

General relativity has a small number of known, exact solutions which model astronomically relevant systems. These models are highly idealized situations. Either perturbation theory or numerical simulations are typically needed to produce more realistic models. Numerical simulations are time-consuming and suffer from a difficulty in interpreting the results. In addition, global properties of numerical solutions are nearly impossible to uncover. On the other hand, standard perturbation methods are very difficult to implement beyond the second order, which means they barely scratch the surface of non-linear phenomena which distinguishes general relativity from Newtonian gravity. This work develops a method of finding exact solutions, inspired by perturbation theory, which have energy-momentum tensor components that approximately satisfy desired relationships. We find a spherical lump of matter which has a density profile μ ∝ r–2 in a Robertson-Walker background; it looks like a galaxy in an expanding universe. We also find a plane-symmetric perturbation of a Bianchi type I metric with a density profile μ ∝ z–2; it models a jet impacting a sheet-like structure. The former solution involves a wormhole while the latter involves a two dimensional singularity. These are both nonlinear structures which perturbation theory can never produce.
Abstraction for Verification and Refutation in Model Checking
Keywords: Model Checking
Abstraction
Verification
Temporal Logic

Model checking is an automated technique for deciding whether a computer program satisfies a temporal property. Abstraction is the key to scaling model checking to industrial-sized problems, which approximates a large (or infinite) program by a smaller abstract model and lifts the model checking result over the abstract model back to the original program. In this thesis, we study abstraction in model checking based on \emph{exact-approximation}, which allows for verification and refutation of temporal properties within the same abstraction framework. Our work in this thesis is driven by problems from both practical and theoretical aspects of exact-approximation. We first address challenges of effectively applying symmetry reduction to \emph{virtually} symmetric programs. Symmetry reduction can be seen as a \emph{strong} exact-approximation technique, where a property holds on the original program if and only if it holds on the abstract model. In this thesis, we develop an efficient procedure for identifying virtual symmetry in programs. We also explore techniques for combining virtual symmetry with symbolic model checking. Our second study investigates model checking of \emph{recursive} programs. Previously, we have developed a software model checker for non-recursive programs based on exact-approximating predicate abstraction. In this thesis, we extend it to reachability and non-termination analysis of recursive programs. We propose a new program semantics that effectively removes call stacks while preserving reachability and non-termination. By doing this, we reduce recursive analysis to non-recursive one, which allows us to reuse existing abstract analysis in our software model checker to handle recursive programs. A variety of \emph{partial} transition systems have been proposed for construction of abstract models in exact-approximation. Our third study conducts a systematic analysis of them from both semantic and logical points of view. We analyze the connection between semantic and logical consistency of partial transition systems, compare the expressive power of different families of these formalisms, and discuss the precision of model checking over them. Abstraction based on exact-approximation uses a uniform framework to prove correctness and detect errors of computer programs. Our results in this thesis provide better understanding of this approach and extend its applicability in practice.
Power MOSFETs with Enhanced Electrical Characteristics
Keywords: Power MOSFETs

The integration of high voltage power transistors with control circuitry to form smart Power Integrated Circuits (PIC) has numerous applications in the areas of industrial and consumer electronics. These smart PICs must rely on the availability of high performance power transistors. In this thesis, a vertical U-shaped gate MOSFET (UMOS) and a lateral Extended Drain MOSFET (EDMOS) with enhanced electrical characteristics are proposed, developed and verified via experimental fabrication. The proposed new process and structure offers superior performance, such as low on-resistance, low gate charge and optimized high breakdown voltage. In the vertical power UMOS, a novel trenched Local Oxidation of Silicon (LOCOS) process has been applied to the vertical gate structure to reduce the gate-to-source overlap capacitance (Cgs). A 40% reduction in Cgs is achieved when compared to conventional UMOS. A specific on-resistance Ron, sp = 60m2·mm2 is observed, which is 45% better than that of the conventional UMOS. The improvement in the device’s Figure-of-Merit (FOM = Ron × Qg) is about 58%. A floating RESURF EDMOS (BV=55V, Ron,sp=36.5m2·mm2) with a 400% improvement in the Safe Operating Area (SOA) when compared to the conventional EDMOS structure is also presented. The proposed EDMOS employs both drain and iii source engineering to enhance SOA, not only via reducing the base resistance of the parasitic bipolar transistor, but also suppressing the base current of the parasitic bipolar transistor under high Vgs and high Vds conditions. A buried deep Nwell allows the device to have better trade-off between breakdown voltage and on-resistance. Finally, in order to achieve low gate charge in the EDMOS, a novel orthogonal gate electrode is proposed to reduce the gate-to-drain overlap capacitance (Cgd). The orthogonal gate has both horizontal and vertical sections for gate control. This device is implemented in a 0.18?m 30V HV-CMOS process. Compared to a conventional EDMOS with the same voltage and size, a 75% Cgd reduction is observed. The FOM is improved by 53%.
Mediated Reality and Location Awareness to Facilitate Topographical Orientation
Keywords: Localization
Navigation

Topographical orientation is the ability to orient oneself within the environment and to navigate through it to specific destinations. Topographical disorientation (TD) refers to deficits in orientation and navigation in the real environment, and is a common sequela of brain injuries. People with TD often have difficulties interacting with and perceiving the surrounding environment. The literature suggests that patients with TD are likely to benefit from research leading to clinical standards of practice and technology to facilitate topographical orientation. In the light of the above, the objectives of this thesis were to investigate methods of realizing a context-aware, wearable mediated environment system for indoor navigation, and to develop a standard method of quantifying the impact of such a system on indoor navigation task performance. In realizing these objectives, we first conducted an extensive literature review of in-door localization systems. This review served to identify potential technologies for an indoor, in-situ wayfinding assistive device. Subsequently, an automated navigation algorithm was designed. Our algorithm reduced the navigational effort of simulated patients with topographical disorientation while accounting for the physical abilities of the patient, environmental barriers and dynamic building changes. We introduced and demonstrated a novel energy-based wayfinding metric, which is independent of route complexity. An experiment was conducted to identify preferred graphical navigation tools for mediated reality wayfinding guidance. Different combinations of spatial knowledge, graphical presentations and reference frames were considered in the experiment. The data suggested that the locator and minimap are the preferred navigational tools. Two unique optical-inertial localization systems for real-time indoor human tracking were created. The first localization system was oriented to pedestrians, while the second was implemented on a wheelchair. Empirical tests produced localization accuracies comparable to those reported in literature. Finally, a fully operational mediated reality location aware system for indoor navigation was realized. Tests with human participants indicated a significant reduction in physical effort in comparison to the no-tool condition, during wayfinding tasks in an unfamiliar indoor environment. Collectively, the findings and developments of this thesis lay the foundation for future research on wearable, location-based navigational assistance for individuals with wayfinding difficulties.
Modeling and Optimization of Delay and Power for Key Components of Modern High-performance Processors
Keywords: Processor design
Computer architecture
Physical-level implementation

In designing a new processor, computer architects consider a myriad of possible organizations and designs to decide which best meets the constraints on performance, power and cost for each particular processor. To identify practical designs, architects need to have insight into the physical-level characteristics (delay, power and area) of various components of modern processors implemented in recent fabrication technologies. During early stages of design exploration, however, developing physical-level implementations for various design options (often in the order of thousands) is impractical or undesirable due to time and/or cost constraints. In lieu of actual measurements, analytical and/or empirical models can offer reasonable estimates of these physical-level characteristics. However, existing models tend to be out-dated for three reasons: (i) They have been developed based on old circuits in old fabrication technologies; (ii) The high-level designs of the components have evolved and older designs may no longer be representative; and, (iii) The overall architecture of processors has changed significantly, and new components for which no models exist have been introduced or are being considered. This thesis studies three key components of modern high-performance processors: Counting Bloom Filters (CBFs), Checkpointed Register Alias Tables (RATs), and Compacted Matrix Schedulers (CMSs). CBFs optimize membership tests (e.g., whether a block is cached). RAT and CMS increase the opportunities for exploiting instruction-level parallelism; RAT is the core of the renaming stage, and CMS is an implementation for the instruction scheduler. Physical-level studies or models for these components have been limited or non-existent. In addition to investigating these components at the physical level, this thesis (i) proposes a novel speed- and energy-efficient CBF implementation; (ii) studies how the number of RAT checkpoints affects its latency and energy, and overall processor performance; and, (iii) studies the CMS and its accompanying logic at the physical level. This thesis also develops empirical and analytical latency and energy models that can be adapted for newer fabrication technologies. Additionally, this thesis proposes physical-level latency and energy optimizations for these components motivated by design inefficiencies exposed during the physical-level study phase.
Disinhibition at Feedforward Inhibitory Synapses in Hippocampal Area CA1 Induces a Form of Long-term Potentiation
Keywords: Synaptic plasticity
Hippocampus

One of the central questions of neuroscience research has been how the cellular and molecular components of the brain give rise to complex behaviours. Three major breakthroughs from the past sixty years have made the study of learning and memory central to our understanding of how the brain works. First, the psychologist Donald Hebb proposed that information storage in the brain could occur through the strengthening of the connections between neurons if the strengthening were restricted to neurons that were co-active (Hebb, 1949). Second, Milner and Scoville (1957) showed that the hippocampus is required for the acquisition of new long-term memories for consciously accessible, or declarative, information. Third, Bliss and Lømo (1973) demonstrated that the synapses between neurons in the dentate gyrus of the hippocampus could indeed be potentiated in an activity-dependent manner. Long-term potentiation (LTP) of the glutamatergic synapses in area CA1, the primary output of the hippocampus, has since become the leading model of synaptic plasticity due to its dependence on NMDA receptors (NMDARs), required for spatial and temporal learning in intact animals, and its robust pathway specificity. Using whole-cell recording in hippocampal slices from adult rats, I find that the efficacy of synaptic transmission from CA3 to CA1 can in fact be enhanced without the induction of classic LTP at the glutamatergic inputs. Taking care not to directly stimulate inhibitory fibers, I show that the induction of GABAergic plasticity at feedforward inhibitory inputs in CA1 results in the reduced shunting of excitatory currents, producing a long-term increase in the amplitude of Schaffer collateral-mediated postsynaptic potentials which is dependent on NMDAR activation and is pathway specific. The sharing of these fundamental properties with classic LTP suggests the possibility of a previously unrecognized target for therapeutic intervention in disorders linked to memory deficits, as well as a potentially overlooked site of LTP expression in other areas of the brain.