Fostering Equitable Foreclosure Recovery

This report provides essential information to inform policy discussions about foreclosure recovery. It presents information about the foreclosure crisis and its consequences, describes the federal program created to help communities recover from the impacts of foreclosures, shares case studies of foreclosure recovery efforts in three regions in the Northwest -- Minneapolis-St. Paul, Portland, and Seattle -- and suggests policy recommendations for ensuring equitable recovery

Biking in Hartford

The city of Hartford lags behind other mid-sized, post-industrial, Northeast cities in the U.S. in biking infrastructure and demand for biking. Since many low-income people without cars must rely on the inefficient bus system and walking, biking can become an alternative option that better mobilizes them to access key institutions such as jobs, education, and healthcare. With a high number of low-income peoples and immigrant groups, Hartford has the potential to expand its demand for biking past many cities. The city of Hartford faces major obstacles that prevents it from developing the most comprehensive biking infrastructure, but with partnerships with the biking community and the use of different strategies to incorporate bike lanes, the city of Hartford can overcome the obstacles. In order to alleviate financial costs, the city of Hartford should aim to focus on the bike lanes that currently exist in the city and develop bike lanes on less busy streets as supposed to main streets. The city of Hartford can consolidate and share resources by partnering with biking community organizations such as individual bike advocates and bicycle co-ops. These individuals and groups have already established programs that connect low-income peoples and immigrants to biking and would highly benefit from the exposure of a partnership with the city of Hartford

The Economic Benefits of Immigrant Authorization in California

The USC Center for the Study of Immigrant Integration (CSII) estimates that California would eventually benefit from Latino immigrant legalization by $16 billion annually. This would work towards fixing our budget crisis and restoring our safety net programs cut by the state last August. During this period of economic struggle and budget woes, California has a lot to gain from a national legalization policy. The report entitled "The Economic Benefits of Immigrant Authorization in California" measures the benefits that would accrue to the state and the nation if the currently unauthorized Latino workforce in California were legalized. CSII researchers used a conservative economic model that accounts for the wage "penalty" incurred by the undocumented, assumes a very slow increase in English skills and educational levels, and does not account for gains from future migration. Despite this conservative modeling, the report finds that significant immediate and long-term benefits would accrue not only to affected workers, but to the state and nation overall

Characterization of ecosystem services associated with deep-sea habitats and natural stormwater treatment systems and their incorporation into environmental management

We, as a society, are notoriously bad at finding balance between extraction of natural resources and environmental protection. The concept of ecosystem services, the direct and indirect benefits derived from the environment, attempts to ameliorate these failures by linking natural processes to human well-being. The goal of this dissertation was to explore approaches for characterizing ecosystem services and to identify how they can be incorporated into environmental management. To do this, I used two groups of systems subject to human impact, deep-sea habitats and natural stormwater treatment systems (NTS), that provided a suite of characteristics with which to compare and contrast (e.g. marine versus terrestrial, level of human impact, ease of access). While deep-sea habitats and NTS provide some of the same ecosystem services, the structures and functions that support them can differ. Mechanisms for incorporating this information into environmental decision-making differ among systems as well. As interest in deep-sea natural resources continues to grow, environmental decision-makers have the novel opportunity to employ an ecosystem services approach, prior to commercial exploitation in cases such as mining. In comparing molecular and morphology-based methods for assessment and monitoring of deep-sea biodiversity, I examined scientific and economic tradeoffs between the two to suggest a combined approach as most cost-effective when considering future environmental requirements. I also leveraged existing deep-sea imagery and biological trait analysis to evaluate fisheries services and climate-regulating services related to carbon at methane seeps off southern California, identifying the Del Mar seep as the largest contributor to ecosystem services. In contrast to the seemingly untouched deep sea, NTS are human-designed to mimic physical and biological processes, which can generate ecosystem services such as climate-regulating services related to carbon. I found that, although urban greenspaces are not carbon sinks, NTS and natural areas are more carbon-efficient than grass lawns and horticultural gardens. NTS present a unique opportunity to manipulate natural structures and functions for targeted benefits, such as carbon sequestration and storage. Together, this body of work serves to operationalize ecosystem services in a multitude of contexts with practical applications

Genetic Characterization of Single-Stranded RNA Phage Lysis Genes

With an ever-increasing incidence of antibiotic resistance in clinical settings, bacterial viruses, or “phages”, are being considered as alternatives to chemical antibiotics. One type of phage in particular, single-stranded RNA (ssRNA) phages, are of interest because they have single gene lysis systems, meaning they employ one gene that, when expressed, causes the host cell to lyse. There are four paradigm single gene lysis systems: L from ssRNA phage MS2, A2 from ssRNA phage Qβ, E from single-stranded DNA phage ϕX174, and Lys from ssRNA phage M. While the mechanism of L is still unknown, lysis proteins A2, E, and Lys have been shown to inhibit steps in peptidoglycan biosynthesis. It is highly likely that lysis proteins from other ssRNA phages also target this pathway. Previously, however, only fourteen single-stranded RNA phages were known. Two separate papers published within the past year have identified over 150 novel ssRNA phage genomes by mining transcriptome and microbiome data (2, 3). The goal of this project is to identify and test potential lysis genes from these genomes and determine the targets of their lysis proteins. Understanding the mechanisms of these novel lysis proteins would potentially allow us to find new antibiotic targets or even develop new antibiotic strategies

Cofactor Selectivity in Methylmalonyl Coenzyme A Mutase, a Model Cobamide-Dependent Enzyme.

Cobamides, a uniquely diverse family of enzyme cofactors related to vitamin B12, are produced exclusively by bacteria and archaea but used in all domains of life. While it is widely accepted that cobamide-dependent organisms require specific cobamides for their metabolism, the biochemical mechanisms that make cobamides functionally distinct are largely unknown. Here, we examine the effects of cobamide structural variation on a model cobamide-dependent enzyme, methylmalonyl coenzyme A (CoA) mutase (MCM). The in vitro binding affinity of MCM for cobamides can be dramatically influenced by small changes in the structure of the lower ligand of the cobamide, and binding selectivity differs between bacterial orthologs of MCM. In contrast, variations in the lower ligand have minor effects on MCM catalysis. Bacterial growth assays demonstrate that cobamide requirements of MCM in vitro largely correlate with in vivo cobamide dependence. This result underscores the importance of enzyme selectivity in the cobamide-dependent physiology of bacteria.IMPORTANCE Cobamides, including vitamin B12, are enzyme cofactors used by organisms in all domains of life. Cobamides are structurally diverse, and microbial growth and metabolism vary based on cobamide structure. Understanding cobamide preference in microorganisms is important given that cobamides are widely used and appear to mediate microbial interactions in host-associated and aquatic environments. Until now, the biochemical basis for cobamide preferences was largely unknown. In this study, we analyzed the effects of the structural diversity of cobamides on a model cobamide-dependent enzyme, methylmalonyl-CoA mutase (MCM). We found that very small changes in cobamide structure could dramatically affect the binding affinity of cobamides to MCM. Strikingly, cobamide-dependent growth of a model bacterium, Sinorhizobium meliloti, largely correlated with the cofactor binding selectivity of S. meliloti MCM, emphasizing the importance of cobamide-dependent enzyme selectivity in bacterial growth and cobamide-mediated microbial interactions

A Quantum Yield Map for Synthetic Eumelanin

The quantum yield of synthetic eumelanin is known to be extremely low and it has recently been reported to be dependent on excitation wavelength. In this paper, we present quantum yield as a function of excitation wavelength between 250 and 500 nm, showing it to be a factor of 4 higher at 250 nm than at 500 nm. In addition, we present a definitive map of the steady-state fluorescence as a function of excitation and emission wavelengths, and significantly, a three-dimensional map of the specific quantum yield: the fraction of photons absorbed at each wavelength that are subsequently radiated at each emission wavelength. This map contains clear features, which we attribute to certain structural models, and shows that radiative emission and specific quantum yield are negligible at emission wavelengths outside the range of 585 and 385 nm (2.2 and 3.2 eV), regardless of excitation wavelength. This information is important in the context of understanding melanin biofunctionality, and the quantum molecular biophysics therein.Comment: 10 pages, 6 figure

Hypoxic Incubator Control System

This paper describes the functionality of the current Hypoxic Incubator, a project started by BMED graduate students Simone Helfrich and Makenzie Jones, with the objective being to redesign the device to address potential areas of improvement. The hypoxic incubator has been designed to allow for the control of the O2, CO2, and N2 levels such that researchers can grow and study cell culture in hypoxic conditions; however, its efficacy and efficiency are limited by the fact that it often overshoots the desired setpoints for O2 and CO2 in addition to being difficult to use due to requiring the operator to understand the basics of coding. These limitations directly translate into the governing customer requirements for our project. Firstly, to address these limitations, a conceptual model was developed to help pinpoint the root cause of overshoot which was determined to be the inability to control the excessive flowrate. Different design concepts were generated to mitigate this issue and were drafted utilizing a morphological analysis. A concept evaluation revealed that the different aspects of our individual design concepts excelled in separate functional categories. As a result, the final design was a Hypoxic Incubator equipped with a new pressure regulator and touchscreen which combined the best aspects of each individual design concept. Detailed test plans were outlined which allowed for validation and verification of our design against customer requirements and engineering specifications. While there were some complications during the test procedure, trends in the test data show that the control system is effective at maintaining the desired gas setpoints necessary to cultivate cells in a hypoxic environment. Specifically, the issue of overshoot that was prevalent in the previous design iteration is now mitigated as CO2 and O2 are kept within their acceptable ranges of +/- 0.5% and +/- 0.1% from the setpoint, respectively. The percentage of time spent outside the acceptable range per one-hour incubation time was less than 1.0% in some tests. Additionally, the newly added touchscreen received a usability score of 4.4 out of 5, indicating that it was easy to use with little to no confusion. While the most pertinent issues are addressed, this paper also highlights some future improvements for the incubation chamber such as the implementation of a PID controller to effectively reduce excess gas usage

Defective phagocytic corpse processing results in neurodegeneration and can be rescued by TORC1 activation

This work was supported by NIH Grants R01 GM094452 (K.M.) and F31 GM099425 (J.I.E.), BU Alzheimer's Disease Core Center NIH Grant P30 AG13846, Boston University Undergraduate Research Opportunities Program grants (J.A.T., V.S.), and NIH Grant R01 AG044113 to M.B.F. We thank the Bloomington Stock Center, TRiP at Harvard Medical School, the Kyoto Drosophila Genetic Resource Center, Estee Kurant, Eric Baehrecke, Marc Freeman, and Mary Logan for fly strains. We thank Todd Blute for assistance with electron microscopy and the Developmental Studies Hybridoma Bank for antibodies. (R01 GM094452 - NIH; F31 GM099425 - NIH; R01 AG044113 - NIH; P30 AG13846 - BU Alzheimer's Disease Core Center NIH Grant; Boston University Undergraduate Research Opportunities Program)https://www.jneurosci.org/content/36/11/3170.longPublished versionPublished versio

The burden of managing pleural effusions in patients with chronic myelogenous leukemia post-imatinib failure: A literature-based economic analysis

Jennifer Stephens, Kimbach Tran Carpiuc, Marc BottemanPharmerit North America LLC, Bethesda, MD, USAObjectives: To develop an economic analysis of the management of pleural effusions in patients with imatinib-resistant/intolerant chronic myelogenous leukemia (CML).Methods: A cost of treatment analysis was conducted from the US payer perspective, based on resource utilization data for 48 patients with dasatinib-related pleural effusions at a large US cancer center. Probabilities of various procedures and treatment events were derived from published resource use data, supplemented with expert opinion. Cost data was derived from median reimbursements for relevant CPT codes for outpatient services and medical literature for inpatient services. Sensitivity analyses were conducted for types of procedures used. All costs were adjusted to US dollars (2007 rates).Results: Sixty percent of pleural effusions were managed medically costing 750 per episode. Forty percent of pleural effusions were more significant (>25% of one lung volume), with half of those requiring invasive procedures. Cost of inpatient procedures was 10,616 for chest tube and $15,170 with pleural catheter. Cost of outpatient procedures was$713 for ultrasound thoracentesis and $4,598 for pleural catheter. The average cost of treating a pleural effusion was$2,062 to >$2,700 for all severity levels and ~$6,400 to >$9,000 for invasive procedures. Key cost drivers were invasive procedures and recurrence.Conclusion: This economic analysis using actually observed treatment patterns suggests that the management of pleural effusion adverse events in CML patients is costly, requires intensive resource utilization, and may be an important factor in treatment selection.Keywords: dasatinib, nilotinib, imatinib, adverse events, safety, cost, and cost analysi