Small Suburbs, Large Lots: How the Scale of Land-Use Regulation Affects Housing Affordability, Equity, and the Climate

Housing costs in major coastal metropolitan areas nationwide have skyrocketed, impacting people, the economy, and the environment. Landuse regulation, controlled primarily at the local level, plays a major role in determining housing production. In response to this mounting housing crisis, scholars, policymakers, and commentators are debating whether greater state involvement in local land-use decision-making is the best path forward. We argue here that there are good reasons to believe that continuing on the current path—with local control of land-use regulation as it is— will lead to persistent underproduction of housing. The benefits of housing production are primarily regional, including improved job markets, increased socioeconomic mobility, and reduced greenhouse gas emissions. But the costs associated with producing more housing are often local, felt at the neighborhood level. Local governments whose voters are impacted by the local negative impacts of housing and will usually have less incentive to consider those regional, and national, benefits and approve housing. Recent political science, planning, economics, and legal research shows that smaller local jurisdictions tend to produce less housing, and when political institutions decentralize control over housing to the sublocal (e.g., neighborhood) scale, less housing is approved. A central theory in academic research in land-use regulation and local government law has been the idea that competition among highly fragmented local governments can produce more efficient outcomes in public services and land-use regulation, even if there may be significant inequities across local jurisdictions in outcomes. Our analysis shows that this theory no longer accurately describes how fragmented local governance affects economic efficiency. Indeed, our analysis makes clear that fragmented local governance is both inequitable and inefficient, at least in the context of land-use regulation. Our analysis also raises questions about local government law scholarship contending that increased local governmental power can effectively address the dysfunctions of metropolitan areas in the United States. We present a range of policy proposals to address the problems we identify. First, greater state intervention in local land-use regulation is necessary. While a greater state role need not (and probably should not) entirely displace local control, it is essential to ensure that the larger-scale benefits of housing are appropriately considered. Second, we note that the highly fragmented local land-use regulatory system imposes challenges for housing production, in part, because variation among local regulatory practices creates barriers to entry for new housing across jurisdictions. Accordingly, we advocate for a state role to increase the standardization of local land-use regulatory tools as a key step to help advance greater housing production, even where local control is maintained

Targeting PI3K-gamma in myeloid driven tumour immune suppression: a systematic review and meta-analysis of the preclinical literature

The intricate interplay between immune and stromal cells within the tumour microenvironment (TME) significantly influences tumour progression. Myeloid cells, including tumour-associated macrophages (TAMs), neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs), contribute to immune suppression in the TME (Nakamura and Smyth in Cell Mol Immunol 17(1):1–12 (2020). https://doi.org/10.1038/s41423-019-0306-1; DeNardo and Ruffell in Nat Rev Immunol 19(6):369–382 (2019). https://doi.org/10.1038/s41577-019-0127-6). This poses a significant challenge for novel immunotherapeutics that rely on host immunity to exert their effect. This systematic review explores the preclinical evidence surrounding the inhibition of phosphoinositide 3-kinase gamma (PI3Kγ) as a strategy to reverse myeloid-driven immune suppression in solid tumours. EMBASE, MEDLINE, and PubMed databases were searched on 6 October 2022 using keyword and subject heading terms to capture relevant studies. The studies, focusing on PI3Kγ inhibition in animal models, were subjected to predefined inclusion and exclusion criteria. Extracted data included tumour growth kinetics, survival endpoints, and immunological responses which were meta-analysed. PRISMA and MOOSE guidelines were followed. A total of 36 studies covering 73 animal models were included in the review and meta-analysis. Tumour models covered breast, colorectal, lung, skin, pancreas, brain, liver, prostate, head and neck, soft tissue, gastric, and oral cancer. The predominant PI3Kγ inhibitors were IPI-549 and TG100-115, demonstrating favourable specificity for the gamma isoform. Combination therapies, often involving chemotherapy, radiotherapy, immune checkpoint inhibitors, biological agents, or vaccines, were explored in 81% of studies. Analysis of tumour growth kinetics revealed a statistically significant though heterogeneous response to PI3Kγ monotherapy, whereas the tumour growth in combination treated groups were more consistently reduced. Survival analysis showed a pronounced increase in median overall survival with combination therapy. This systematic review provides a comprehensive analysis of preclinical studies investigating PI3Kγ inhibition in myeloid-driven tumour immune suppression. The identified studies underscore the potential of PI3Kγ inhibition in reshaping the TME by modulating myeloid cell functions. The combination of PI3Kγ inhibition with other therapeutic modalities demonstrated enhanced antitumour effects, suggesting a synergistic approach to overcome immune suppression. These findings support the potential of PI3Kγ-targeted therapies, particularly in combination regimens, as a promising avenue for future clinical exploration in diverse solid tumour types

Reconsidering "the love of art" : evaluating the potential of art museum outreach

Art museums have long been identified as bastions of social and cultural exclusion. This conclusion was best evidenced by the large-scale 1967 French study by Bourdieu and Darbel demonstrating the exclusionary nature of “The Love of Art.” However, in recent years there have been increasing efforts to reach out to a broader range of visitors beyond conventional audiences. The present study investigates the impacts of an outreach program at a UK art museum, which sought to engage socially excluded young mothers. This study employs ethnographic research methods on a longitudinal basis to develop qualitative insights about the program seeking to mitigate cultural exclusion. While the study’s findings uphold many longstanding critiques of art museums’ conventional approaches, the study also indicates that carefully designed outreach activities can overcome such limitations and enhance cultural engagement. Thus, art museums’ limited appeal is tied to problematic public engagement practices that can be changed

Cryptic Diversity and Conservation of Gopher Frogs across the Southeastern United States

Identifying cryptic biodiversity is fundamental to evolutionary biology and to conservation efforts. This study investigated range-wide genetic diversity of Gopher Frogs, Lithobates capito, across the southeastern United States coastal plain to determine implications for taxonomy and conservation. We collected data for two mtDNA regions in 21 populations to identify genetic structure across the geographic distribution of the species. Based on population genetic, phylogenetic, and genealogical analyses, we recovered three reciprocally monophyletic mtDNA lineages corresponding to mainland coastal plain populations and two lineages within peninsular Florida. Breakpoints for these lineages did not occur in previously identified hotspots of amphibian phylogeographic breaks and did not follow currently recognized subspecies designations. We recommend these lineages be recognized as separate distinct population segments and be considered separately by the U.S. Fish and Wildlife Service for listing under the Endangered Species Act. Additionally, we propose an evolutionary hotspot for amphibians that deserves further attentio

Anticancer Properties of Carnosol: A Summary of In Vitro and In Vivo Evidence

Cancer is characterized by unrestricted cell proliferation, inhibition of apoptosis, enhanced invasion and migration, and deregulation of signalling cascades. These properties lead to uncontrolled growth, enhanced survival, and the formation of tumours. Carnosol, a naturally occurring phyto-polyphenol (diterpene) found in rosemary, has been studied for its extensive antioxidant, anti-inflammatory, and anticancer effects. In cancer cells, carnosol has been demonstrated to inhibit cell proliferation and survival, reduce migration and invasion, and significantly enhance apoptosis. These anticancer effects of carnosol are mediated by the inhibition of several signalling molecules including extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt, mechanistic target of rapamycin (mTOR) and cyclooxygenase-2 (COX-2). Additionally, carnosol prevents the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and promotes apoptosis, as indicated by increased levels of cleaved caspase-3, -8, -9, increased levels of the pro-apoptotic marker Bcl-2-associated X (BAX), and reduced levels of the anti-apoptotic marker B-cell lymphoma 2 (Bcl-2). The current review summarizes the existing in vitro and in vivo evidence examining the anticancer effects of carnosol across various tissues

Mapping evaporative water loss in desert passerines reveals an expanding threat of lethal dehydration

Extreme high environmental temperatures produce a variety of consequences for wildlife, including mass die-offs. Heat waves are increasing in frequency, intensity, and extent, and are projected to increase further under climate change. However, the spatial and temporal dynamics of die-off risk are poorly understood. Here, we examine the effects of heat waves on evaporative water loss (EWL) and survival in five desert passerine birds across the southwestern United States using a combination of physiological data, mechanistically informed models, and hourly geospatial temperature data. We ask how rates of EWL vary with temperature across species; how frequently, over what areas, and how rapidly lethal dehydration occurs; how EWL and die-off risk vary with body mass; and how die-off risk is affected by climate warming. We find that smaller-bodied passerines are subject to higher rates of mass-specific EWL than larger-bodied counterparts and thus encounter potentially lethal conditions much more frequently, over shorter daily intervals, and over larger geographic areas. Warming by 4 °C greatly expands the extent, frequency, and intensity of dehydration risk, and introduces new threats for larger passerine birds, particularly those with limited geographic ranges. Our models reveal that increasing air temperatures and heat wave occurrence will potentially have important impacts on the water balance, daily activity, and geographic distribution of arid-zone birds. Impacts may be exacerbated by chronic effects and interactions with other environmental changes. This work underscores the importance of acute risks of high temperatures, particularly for small-bodied species, and suggests conservation of thermal refugia and water sources

In Situ Transfection by Controlled Release of Lipoplexes Using Acoustic Droplet Vaporization

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133565/1/adhm201600008_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133565/2/adhm201600008.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133565/3/adhm201600008-sup-0001-S1.pd

Time course analysis of gene expression identifies multiple genes with differential expression in patients with in-stent restenosis

Abstract Background The vascular disease in-stent restenosis (ISR) is characterized by formation of neointima and adverse inward remodeling of the artery after injury by coronary stent implantation. We hypothesized that the analysis of gene expression in peripheral blood mononuclear cells (PBMCs) would demonstrate differences in transcript expression between individuals who develop ISR and those who do not. Methods and Results We determined and investigated PBMC gene expression of 358 patients undergoing an index procedure to treat in de novo coronary artery lesions with bare metallic stents, using a novel time-varying intercept model to optimally assess the time course of gene expression across a time course of blood samples. Validation analyses were conducted in an independent sample of 97 patients with similar time-course blood sampling and gene expression data. We identified 47 probesets with differential expression, of which 36 were validated upon independent replication testing. The genes identified have varied functions, including some related to cellular growth and metabolism, such as the NAB2 and LAMP genes. Conclusions In a study of patients undergoing bare metallic stent implantation, we have identified and replicated differential gene expression in peripheral blood mononuclear cells, studied across a time series of blood samples. The genes identified suggest alterations in cellular growth and metabolism pathways, and these results provide the basis for further specific functional hypothesis generation and testing of the mechanisms of ISR.http://deepblue.lib.umich.edu/bitstream/2027.42/112500/1/12920_2010_Article_214.pd

Swimming in circles: Motion of bacteria near solid boundaries

Near a solid boundary, E. coli swims in clockwise circular motion. We provide a hydrodynamic model for this behavior. We show that circular trajectories are natural consequences of force-free and torque-free swimming, and the hydrodynamic interactions with the boundary, which also leads to a hydrodynamic trapping of the cells close to the surface. We compare the results of the model with experimental data and obtain reasonable agreement. In particular, we show that the radius of curvature of the trajectory increases with the length of the bacterium body.Comment: Also available at http://people.deas.harvard.edu/~lauga