Wheels When Who Wants Them: Assessing Social Equity and Access Implications of Carsharing in NYC

Carsharing operations such as Zipcar have grown in popularity in the last two decades, and provide a case study for examining transportation equity. These programs provide a vehicle to rent by the hour or day usually based on an hourly fee and an annual membership fee. The service provides a transportation alternative that could reduce economic and environmental costs of car use, and increase access -- ultimately creating a more sustainable transportation network. However, as with many transportation investments, it is unclear whether these benefits are actually accruing to those with the most limited transport options. Governments subsidize carsharing operations through free parking for shared vehicles; New York City has even altered its zoning code to promote carsharing and encourages the system through PlaNYC 2030. Public subsidization provides the impetus for analyzing private carshare providers through a social justice framework. This thesis will examine whether the distribution of Zipcars (the largest carsharing operator in NYC) is socially equitable, and whether carsharing could potentially increase transport equity through alternative carshare models. The study uses mixed methods including spatial and statistical analysis of carshare density to determine if shared vehicles are correlated with equity variables, controlling for feasibility indicators. This research also includes an intercept survey to determine the barriers and potential of carsharing for non-work trips. The results indicate that shared vehicle density is most closely related to low car ownership, high level of alternative commuters, and high level of education; and that both spatial and corporate barriers exclude segments of the public from participating in the service. Expanding the opportunity to access carsharing through community-based innovations and government intervention could create a more equitable and sustainable transportation system

Exploration of a Novel Approach to Measure Brain Smudging in Dancers

Objective Obtain baseline accuracy measurements of right/left discrimination in actively performing dancers without performance-inhibiting injuries. Purpose Gather data that can be used in future studies to expand understanding of brain smudging in dancers. Methods This study is a prognostic cohort study. This study will involve participant use of a simple iPad application to do the left and right discrimination test that is suggested to give information on brain reorganization, or brain smudging Research Problem The specific physical, mental, and emotional demands of dancers’ careers put constant strain on their bodies to perform at the level required and can lead to injury or a higher risk for reinjury. 1,2,3,4Traditional interventions often do not address central consequences of injury on the body, such as motor cortex reorganization, or brain smudging. 5,6The degree of brain smudging that occurs in injured dancers is currently unknown. Ability to discriminate between right and left sides of the body has been proposed as a means of measuring this smudging.7,8,9,1 Results Mean accuracies out of 100 were as follows: right hand was 62.73 (n=22, SD=23.53), left hand was 61.36 (n=22, SD=16.99), right foot was 94.09 (n=22,SD=11.41), and left foot was 91.82 (n=22, SD=14.02). Conclusions The heavier workload that is typically placed on the lower extremities relative to the upper extremities may explain some of the lower accuracy in the hands in this population. 1,2 Further research is needed to establish scores in those with current injuries and determine whether those scores are predictive of future injury

A strategy for constructing aneuploid yeast strains by transient nondisjunction of a target chromosome

<p>Abstract</p> <p>Background</p> <p>Most methods for constructing aneuploid yeast strains that have gained a specific chromosome rely on spontaneous failures of cell division fidelity. In <it>Saccharomyces cerevisiae</it>, extra chromosomes can be obtained when errors in meiosis or mitosis lead to nondisjunction, or when nuclear breakdown occurs in heterokaryons. We describe a strategy for constructing N+1 disomes that does not require such spontaneous failures. The method combines two well-characterized genetic tools: a conditional centromere that transiently blocks disjunction of one specific chromosome, and a duplication marker assay that identifies disomes among daughter cells. To test the strategy, we targeted chromosomes III, IV, and VI for duplication.</p> <p>Results</p> <p>The centromere of each chromosome was replaced by a centromere that can be blocked by growth in galactose, and <it>ura3::HIS3</it>, a duplication marker. Transient exposure to galactose induced the appearance of colonies carrying duplicated markers for chromosomes III or IV, but not VI. Microarray-based comparative genomic hybridization (CGH) confirmed that disomic strains carrying extra chromosome III or IV were generated. Chromosome VI contains several genes that are known to be deleterious when overexpressed, including the beta-tubulin gene <it>TUB2</it>. To test whether a tubulin stoichiometry imbalance is necessary for the apparent lethality caused by an extra chromosome VI, we supplied the parent strain with extra copies of the alpha-tubulin gene <it>TUB1</it>, then induced nondisjunction. Galactose-dependent chromosome VI disomes were produced, as revealed by CGH. Some chromosome VI disomes also carried extra, unselected copies of additional chromosomes.</p> <p>Conclusion</p> <p>This method causes efficient nondisjunction of a targeted chromosome and allows resulting disomic cells to be identified and maintained. We used the method to test the role of tubulin imbalance in the apparent lethality of disomic chromosome VI. Our results indicate that a tubulin imbalance is necessary for disomic VI lethality, but it may not be the only dosage-dependent effect.</p

Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance

The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging

Characterizing and Overriding the Structural Mechanism of the Quizartinib-Resistant FLT3 “Gatekeeper” F691L Mutation with PLX3397

Tyrosine kinase domain mutations are a common cause of acquired clinical resistance to tyrosine kinase inhibitors (TKIs) used to treat cancer, including the FLT3 inhibitor quizartinib. Mutation of kinase “gatekeeper” residues, which control access to an allosteric pocket adjacent to the ATP-binding site, have been frequently implicated in TKI resistance. The molecular underpinnings of gatekeeper mutation-mediated resistance are incompletely understood. We report the first co-crystal structure of FLT3 with the TKI quizartinib, which demonstrates that quizartinib binding relies on essential edge-to-face aromatic interactions with the gatekeeper F691 residue, and F830 within the highly conserved DFG motif in the activation loop. This reliance makes quizartinib critically vulnerable to gatekeeper and activation loop substitutions while minimizing the impact of mutations elsewhere. Moreover, we identify PLX3397, a novel FLT3 inhibitor that retains activity against the F691L mutant due to a binding mode that depends less vitally on specific interactions with the gatekeeper position