284 research outputs found

    Analysis and Recommendations to Improve Traffic Safety & Flow for Pedestrians Bicyclists and Motorists Along Franklin Street

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    Franklin Street is a minor arterial servicing Portland, Maine that connects Commercial Street and Route 1 to I-295 and has been a target for redevelopment for some time. Franklin is the epitome of traffic congestion, and has unsafe conditions for pedestrians, bicyclists and motorists alike. Portland is the biggest city in Maine and is an important hub for employment, housing and tourism throughout the year. As the city grows, there is a greater demand to build more sustainable, multi-use streets to service all modes of transportation that supports business development, open space and growth. This new vision is being applied to all sectors of the city from pedestrian and bicycle considerations, to neighborhoods, housing, the waterfront and beyond. The key issue is how do you apply these concepts to improve pedestrian, bicycle and traffic safety and flow along Franklin Street in Portland, Maine. The main goal of this research is to see if previous reports and analysis, done by outside consultants and city planners, fit the city’s vision and effectively improve the corridor. One of the concerns being that the city may be focusing too much on the idea and not on how to implement the ideas in a practical way. Namely, will the designs and suggestions properly reduce traffic congestion while improving pedestrian and bicycle safety? The approach used in this thesis is to look at this problem by understanding the history and current conditions, what sectors of Portland affect Franklin Street the most and how they tie into the vision, analyzing future traffic models and data at a worst case scenario and making suggestions to improve pedestrian and bicycle safety based on that scenario. Based on the research and analysis, the city does a good job of making suggestions to improve Franklin Street to coincide with the their vision. However, it seems that the City planners have been more focused on the idea of creating a multi-use, sustainable corridor rather than making sure they effectively mitigate conditions for future traffic growth of all road-user categories. Their suggestions could help improve traffic now as well as support business growth, open space and safety improvements, but what will it do for the future? Would we be back to similar conditions with congestion and safety issues as we see today? This thesis looks to help answer these questions and make suggestion to properly improve Franklin Street. I propose and recommend improvements based on three geometric layouts for Franklin Street combined with analysis from this thesis to provide the best solution

    Co-movement of astral microtubules, organelles and F-actin by dynein and actomyosin forces in frog egg cytoplasm

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    © The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Pelletier, J. F., Field, C. M., Furthauer, S., Sonnett, M., & Mitchison, T. J. Co-movement of astral microtubules, organelles and F-actin by dynein and actomyosin forces in frog egg cytoplasm. Elife, 9, (2020): e60047, https://doi.org/10.7554/eLife.60047.How bulk cytoplasm generates forces to separate post-anaphase microtubule (MT) asters in Xenopus laevis and other large eggs remains unclear. Previous models proposed that dynein-based, inward organelle transport generates length-dependent pulling forces that move centrosomes and MTs outwards, while other components of cytoplasm are static. We imaged aster movement by dynein and actomyosin forces in Xenopus egg extracts and observed outward co-movement of MTs, endoplasmic reticulum (ER), mitochondria, acidic organelles, F-actin, keratin, and soluble fluorescein. Organelles exhibited a burst of dynein-dependent inward movement at the growing aster periphery, then mostly halted inside the aster, while dynein-coated beads moved to the aster center at a constant rate, suggesting organelle movement is limited by brake proteins or other sources of drag. These observations call for new models in which all components of the cytoplasm comprise a mechanically integrated aster gel that moves collectively in response to dynein and actomyosin forces.This work was supported by NIH grant R35GM131753 (TJM) and MBL fellowships from the Evans Foundation, MBL Associates, and the Colwin Fund (TJM and CMF). JFP was supported by the Fannie and John Hertz Foundation, the Fakhri lab at MIT, the MIT Department of Physics, and the MIT Center for Bits and Atoms

    Biomechanical evaluation of shape-memory alloy staples for internal fixation—an in vitro study

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    Background: The field of orthopaedics is a constantly evolving discipline. Despite the historical success of plates, pins and screws in fracture reduction and stabilisation, there is a continuing search for more efficient and improved methods of fracture fixation. The aim of this study was to evaluate shape-memory staples and to compare them to a currently used implant for internal fracture fixation. Multi-plane bending stability and interfragmentary compression were assessed across a simulated osteotomy using single and double-staple fixation and compared to a bridging plate. Methods: Transverse osteotomies were made in polyurethane blocks (20 × 20 × 120 mm) and repairs were performed with one (n = 6), or two (n = 6) 20 mm nitinol staples, or an eight-hole 2.7 mm quarter-tubular plate (n = 6). A pressure film was placed between fragments to determine contact area and compressive forces before and after loading. Loading consisted of multi-planar four-point bending with an actuator displacement of 3 mm. Gapping between segments was recorded to determine loads corresponding to a 2 mm gap and residual post-load gap. Results: Staple fixations showed statistically significant higher mean compressive loads and contact areas across the osteotomy compared to plate fixations. Double-staple constructs were superior to single-staple constructs for both parameters (p < 0.001). Double-staple constructs were significantly stiffer and endured significantly larger loads before 2 mm gap formation compared to other constructs in the dorsoventral plane (p < 0.001). However, both staple constructs were significantly less stiff and tolerated considerably lower loads before 2 mm gap formation when compared to plate constructs in the ventrodorsal and right-to-left lateral loading planes. Loading of staple constructs showed significantly reduced permanent gap formation in all planes except ventrodorsally when compared to plate constructs. Conclusions: Although staple fixations were not as stable as plate fixations in particular loading planes, double-staple constructs demonstrated the most consistent bending stiffness in all planes. Placing two perpendicular staples is suggested instead of single-staples whenever possible, with at least one staple applied on the compression side of the anticipated loading to improve construct stability

    Gaze differences in configural and elemental evaluation during multi-attribute decision-making

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    IntroductionWhile many everyday choices are between multi-attribute options, how attribute values are integrated to allow such choices remains unclear. Recent findings suggest a distinction between elemental (attribute-by-attribute) and configural (holistic) evaluation of multi-attribute options, with different neural substrates. Here, we asked if there are behavioral or gaze pattern differences between these putatively distinct modes of multi-attribute decision-making.MethodsThirty-nine healthy men and women learned the monetary values of novel multi-attribute pseudo-objects (fribbles) and then made choices between pairs of these objects while eye movements were tracked. Value was associated with individual attributes in the elemental condition, and with unique combinations of attributes in the configural condition. Choice, reaction time, gaze fixation time on options and individual attributes, and within- and between-option gaze transitions were recorded.ResultsThere were systematic behavioral differences between elemental and configural conditions. Elemental trials had longer reaction times and more between-option transitions, while configural trials had more within-option transitions. The effect of last fixation on choice was more pronounced in the configural condition.DiscussionWe observed differences in gaze patterns and the influence of last fixation location on choice in multi-attribute value-based choices depending on how value is associated with those attributes. This adds support for the claim that multi-attribute option values may emerge either elementally or holistically, reminiscent of similar distinctions in multi-attribute object recognition. This may be important to consider in neuroeconomics research that involve visually-presented complex objects

    Cosmological Studies with Radio Galaxies and Supernovae

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    Physical sizes of extended radio galaxies can be employed as a cosmological "standard ruler", using a previously developed method. Eleven new radio galaxies are added to our previous sample of nineteen sources, forming a sample of thirty objects with redshifts between 0 and 1.8. This sample of radio galaxies are used to obtain the best fit cosmological parameters in a quintessence model in a spatially flat universe, a cosmological constant model that allows for non-zero space curvature, and a rolling scalar field model in a spatially flat universe. Results obtained with radio galaxies are compared with those obtained with different supernova samples, and with combined radio galaxy and supernova samples. Results obtained with different samples are consistent, suggesting that neither method is seriously affected by systematic errors. Best fit radio galaxy and supernovae model parameters determined in the different cosmological models are nearly identical, and are used to determine dimensionless coordinate distances to supernovae and radio galaxies, and distance moduli to the radio galaxies. The distance moduli to the radio galaxies can be combined with supernovae samples to increase the number of sources, particularly high-redshift sources, in the samples. The constraints obtained here with the combined radio galaxy plus supernovae data set in the rolling scalar field model are quite strong. The best fit parameter values suggest a value of omega is less than about 0.35, and the model parameter alpha is close to zero; that is, a cosmological constant provides a good description of the data. We also obtain new constraints on the physics of engines that power the large-scale radio emission.Comment: 32 pages. Accepted for publication in the Astrophysical Journa

    Assessment of the longitudinal humoral response in non-hospitalized SARS-CoV-2-positive individuals at decentralized sites: Outcomes and concordance

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    IntroductionEarly in the COVID-19 pandemic, reagent availability was not uniform, and infrastructure had to be urgently adapted to undertake COVID-19 surveillance.MethodsBefore the validation of centralized testing, two enzyme-linked immunosorbent assays (ELISA) were established independently at two decentralized sites using different reagents and instrumentation. We compared the results of these assays to assess the longitudinal humoral response of SARS-CoV-2-positive (i.e., PCR-confirmed), non-hospitalized individuals with mild to moderate symptoms, who had contracted SARSCoV-2 prior to the appearance of variants of concern in Québec, Canada.ResultsThe two assays exhibited a high degree of concordance to identify seropositive individuals, thus validating the robustness of the methods. The results also confirmed that serum immunoglobulins persist ≥ 6 months post-infection among non-hospitalized adults and that the antibodies elicited by infection cross-reacted with the antigens from P.1 (Gamma) and B.1.617.2 (Delta) variants of concern.DiscussionTogether, these results demonstrate that immune surveillance assays can be rapidly and reliably established when centralized testing is not available or not yet validated, allowing for robust immune surveillance

    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

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    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

    Targeting oncoprotein translation with rocaglates in MYC-driven lymphoma

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    Published in final edited form as: Leukemia. 2020 January ; 34(1): 138–150. doi:10.1038/s41375-019-0503-z.MYC-driven lymphomas, especially those with concurrent MYC and BCL2 dysregulation, are currently a challenge in clinical practice due to rapid disease progression, resistance to standard chemotherapy and high risk of refractory disease. MYC plays a central role by coordinating hyperactive protein synthesis with upregulated transcription in order to support rapid proliferation of tumor cells. Translation initiation inhibitor rocaglates have been identified as the most potent drugs in MYC-driven lymphomas as they efficiently inhibit MYC expression and tumor cell viability. We found that this class of compounds can overcome eIF4A abundance by stabilizing target mRNA-eIF4A interaction that directly prevents translation. Proteome-wide quantification demonstrated selective repression of multiple critical oncoproteins in addition to MYC in B cell lymphoma including NEK2, MCL1, AURKA, PLK1, and several transcription factors that are generally considered undruggable. Finally, (−)-SDS-1–021, the most promising synthetic rocaglate, was confirmed to be highly potent as a single agent, and displayed significant synergy with the BCL2 inhibitor ABT199 in inhibiting tumor growth and survival in primary lymphoma cells in vitro and in patient-derived xenograft mouse models. Overall, our findings support the strategy of using rocaglates to target oncoprotein synthesis in MYC-driven lymphomas.Accepted manuscrip
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