Amenity or Necessity? Street Standards as Parking Policy, Research Report 11-23

This paper explores the rationales underlying the use of minimum street width requirements to mandate street parking. A survey of 97 cities reveals that this mandate is not a technical necessity based on safety concerns or an amenity reflecting market demand, two common beliefs held by decision-makers. Many residents are likely unwilling to pay for street parking if it is unbundled from housing. The hidden parking policies should be made transparent and subject to public oversight, the double standard between private and public streets should be eliminated, and parking on residential streets should be optional

Residential On-Site Carsharing and Off-Street Parking Policy in the San Francisco Bay Area, Research Report 11-28

In light of rising motorization, transportation planners have increasingly supported alternatives to the indiscriminate use of the car. Off-street parking policy and carsharing have emerged as credible alternatives for discouraging car ownership. This report explores an initiative that could connect these policy fields and build on their synergy: the provision of on-site carsharing service in residential developments. It evaluates the performance of on-site carsharing programs in the San Francisco Bay Area by interviewing developers, planners, and carsharing service providers. Interviews were conducted in four Bay Area cities that support the provision of carsharing as an alternative to the private automobile. Based on these interviews, this report identifies the principal factors contributing to the success or failure of on-site carsharing: the unbundling status of off-street parking in residential developments; ties to off-street parking standards; financial constraints; and the level of coordination among stakeholders. The interviews revealed that on-site carsharing has been accepted by developers, planners, and service providers, particularly in densely-populated, transit-rich communities. Nevertheless, there appears to be a gap between on-site carsharing programs and off-street parking standards, and between carsharing programs and carsharing business operations. The authors recommend that a few models for establishing carsharing policy be tested: a model designed to serve high-density cities with traditional carsharing; and another designed to serve moderately-dense communities, with new carsharing options (e.g., peer-to-peer). In the case of the latter, trip reduction can be achieved through the promotion of alternative modes along major corridors

An Invariant Learning Characterization of Controlled Text Generation

Controlled generation refers to the problem of creating text that contains stylistic or semantic attributes of interest. Many approaches reduce this problem to training a predictor of the desired attribute. For example, researchers hoping to deploy a large language model to produce non-toxic content may use a toxicity classifier to filter generated text. In practice, the generated text to classify, which is determined by user prompts, may come from a wide range of distributions. In this paper, we show that the performance of controlled generation may be poor if the distributions of text in response to user prompts differ from the distribution the predictor was trained on. To address this problem, we cast controlled generation under distribution shift as an invariant learning problem: the most effective predictor should be invariant across multiple text environments. We then discuss a natural solution that arises from this characterization and propose heuristics for selecting natural environments. We study this characterization and the proposed method empirically using both synthetic and real data. Experiments demonstrate both the challenge of distribution shift in controlled generation and the potential of invariance methods in this setting.Comment: To appear in the 2023 Conference of the Association for Computational Linguistics (ACL 2023

Transcriptional landscape of epithelial and immune cell populations revealed through FACS-seq of healthy human skin.

Human skin consists of multiple cell types, including epithelial, immune, and stromal cells. Transcriptomic analyses have previously been performed from bulk skin samples or from epithelial and immune cells expanded in cell culture. However, transcriptomic analysis of bulk skin tends to drown out expression signals from relatively rare cells while cell culture methods may significantly alter cellular phenotypes and gene expression profiles. To identify distinct transcriptomic profiles of multiple cell populations without substantially altering cell phenotypes, we employed a fluorescence activated cell sorting method to isolate keratinocytes, dendritic cells, CD4+ T effector cells, and CD8+ T effector cells from healthy skin samples, followed by RNA-seq of each cell population. Principal components analysis revealed distinct clustering of cell types across samples, while differential expression and coexpression network analyses revealed transcriptional profiles of individual cell populations distinct from bulk skin, most strikingly in the least abundant CD8+ T effector population. Our work provides a high resolution view of cutaneous cellular gene expression and suggests that transcriptomic profiling of bulk skin may inadequately capture the contribution of less abundant cell types

Adoptive Treg Cell Therapy in a Patient With Systemic Lupus Erythematosus.

ObjectiveAdoptive Treg cell therapy has great potential to treat autoimmune disease. Currently, very little is known about how these cells impact inflamed tissues. This study was undertaken to elucidate how autologous Treg cell therapy influences tissue inflammation in human autoimmune disease.MethodsWe describe a systemic lupus erythematosus (SLE) patient with active skin disease who received adoptive Treg therapy. We comprehensively quantified Treg cells and immune activation in peripheral blood and skin, with data obtained at multiple time points posttreatment.ResultsDeuterium tracking of infused Treg cells revealed the transient presence of cells in peripheral blood, accompanied by increased percentages of highly activated Treg cells in diseased skin. Flow cytometric analysis and whole transcriptome RNA sequencing revealed that Treg cell accumulation in skin was associated with a marked attenuation of the interferon-γ pathway and a reciprocal augmentation of the interleukin-17 (IL-17) pathway. This phenomenon was more pronounced in skin relative to peripheral blood. To validate these findings, we investigated Treg cell adoptive transfer of skin inflammation in a murine model and found that it also resulted in a pronounced skewing away from Th1 immunity and toward IL-17 production.ConclusionWe report the first case of a patient with SLE treated with autologous adoptive Treg cell therapy. Taken together, our results suggest that this treatment leads to increased activated Treg cells in inflamed skin, with a dynamic shift from Th1 to Th17 responses

Regulatory T cells use arginase 2 to enhance their metabolic fitness in tissues

Distinct subsets of Tregs reside in nonlymphoid tissues where they mediate unique functions. To interrogate the biology of tissue Tregs in human health and disease, we phenotypically and functionally compared healthy skin Tregs with those in peripheral blood, inflamed psoriatic skin, and metastatic melanoma. The mitochondrial enzyme, arginase 2 (ARG2), was preferentially expressed in Tregs in healthy skin, increased in Tregs in metastatic melanoma, and reduced in Tregs from psoriatic skin. ARG2 enhanced Treg suppressive capacity in vitro and conferred a selective advantage for accumulation in inflamed tissues in vivo. CRISPR-mediated deletion of this gene in primary human Tregs was sufficient to skew away from a tissue Treg transcriptional signature. Notably, the inhibition of ARG2 increased mTOR signaling, whereas the overexpression of this enzyme suppressed it. Taken together, our results suggest that Tregs express ARG2 in human tissues to both regulate inflammation and enhance their metabolic fitness