136 research outputs found
Daily Dying: The Gateway to Living Well
No full textDr. Ravi Ravindra marries deep studies in both science and comparative religions to explore important questions of our age. In this community conversation, he will help us explore how holding an understanding of our own mortality can enrich our living.
Dr. Ravindra’s spiritual search has led him to the teachings of J. Krishnamurti, G. I. Gurdjieff, Zen, Yoga, and a deep immersion in the mystical teachings of the Indian and Christian classical traditions. He is the author of several books on religion, science, mysticism, and spirituality, including Whispers from the Other Shore: Spiritual Search--East and West, and Science and the Sacred: Eternal Wisdom in a Changing World.
Using these lenses, Dr. Ravindra will help us explore the questions that facing our own mortality brings to the surface, both personally and culturally. Mainstream American culture has a paradoxical relationship with dying. On the one hand, our media focuses on death through violence and war, and on the other hand, although we are all moving toward death from the moment of our birth, we turn away from the intimacy of considering our own dying or the death of those we love
Validation of Dosimetric Leaf Gap (DLG) prior to its implementation in Treatment Planning System (TPS): TrueBeam™ millennium 120 leaf MLC
No full textMicroRNAs Function as Cis- and Trans- Acting Modulators of Clock Gene Expression in SCN and Peripheral Circadian Oscillators
Get PDFThe circadian system in mammals is arranged as a hierarchical network of oscillators, with the master pacemaker of circadian rhythms located in the suprachiasmatic nuclei (SCN) of the hypothalamus and peripheral oscillators in most other organ and tissue systems of the body. The molecular machinery responsible for generating circadian rhythms is composed of interlocked transcriptional-translational feedback loops with the gene Brain Muscle Arnt-like 1 (Bmal1) functioning as a core positive regulator. Using the mouse, Mus musculus as a model system, we studied the post-transcriptional mechanisms regulating Bmal1 expression in the SCN pacemaker and in peripheral oscillators.
Target prediction algorithms were used to identify microRNAs (miRNAs) predicted to target Bmal1. We profiled the temporal expression of miR-142-3p in the mouse SCN in vivo and in an immortalized SCN cell line and observed robust circadian rhythms in its expression in the SCN. Following luciferase-reporter and site-directed mutagenesis analyses, we identified miR-142-3p as a bona-fide post-transcriptional repressor of Bmal1. The temporal expression of potential Bmal1-targeting miRNAs was also examined in the circulation in mouse serum. In mice housed in a light-dark cycle, diurnal oscillations were observed in serum levels of miR-152 and miR-494, but not miR-142-3p expression. Luciferase reporter studies indicated that miR-494, both independently and synergistically with miR-142-3p, repressed the Bmal1 3��� UTR. Overexpression of these miRNAs disrupted ensemble circadian rhythms of PER2::LUCIFERASE activity in cultured fibroblasts. Overexpression of the miRNAs also increased their extracellular levels and their intracellular accumulation in recipient cultures exposed to conditioned medium. Furthermore, inhibition of exocytosis and endocytosis affected ensemble circadian rhythms in cultured fibroblasts.
The results thus implicate miR-142-3p and miR-494 in the regulation of Bmal1 expression in the SCN and peripheral oscillators and suggest that miRNAs may function as both, intracellular and extracellular (cis- and trans- acting) signals, modulating the core clock mechanism in the SCN and in fine-tuning the synchronization of circadian rhythmicity between cell-autonomous oscillators in the periphery
Emotion deep dive for designers: Seven propositions that operationalize emotions in design innovation
No full textThis paper presents a five-day intense course that teaches “emotion-driven design”(EDD) to graduate students with a broad variety of disciplinary backgrounds at theFaculty of Psychology, Beijing Normal University. We introduce seven principlesdrawn from design-relevant emotion knowledge that informed the design of thecourse’s overall structure, and explain how they guided the development of learningactivities and materials. We envision that this paper will interest design educatorswho aspire teaching how to operationalize emotions in creative design processes tostudents with little preexisting expertise in (or scientific knowledge about) emotionpsychology.Human-Centered DesignDesign Aesthetic
Mitigation of passenger effects of state of good repair projects using automated data sources
No full textThis electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Thesis: S.M. in Transportation, Massachusetts Institute of Technology, Department of Urban Studies and Planning, 2019Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 169-172).Legacy urban rail transit systems in North America increasingly face challenges in maintaining their infrastructure to provide reliable, effective, and safe service and absorb future growth in cities, which makes scheduled service disruptions to implement State of Good Repair (SGR) projects imminent. Mitigating the impacts of these disruptions on passengers is important in order to maintain transit ridership in the face of competing transportation network company services. Transit agencies have access to large amounts of passenger and vehicle location data, which provide valuable information regarding passenger travel patterns and service levels. This thesis presents a framework for incorporating passenger effects and their mitigation in planning for SGR project shutdowns using the data sources available to transit agencies, with relevant criteria for informing decisions proposed at each stage of the framework.The thesis focuses on passenger impact mitigation in two aspects: selection of work plan, and identification and planning of existing alternative services within the system. From passenger travel patterns, the effects of a shutdown can be gaged, and the impact can be quantified in terms of additional passenger hours. This measure would vary by time of day, day of week, and season, and can be used to determine a shutdown work plan which is less disruptive to passengers. For a particular shutdown plan, connectivity within the transit system implies that some passengers could benefit by using alternative services on existing routes instead of station-to-station bus shuttles.The proposed framework presents criteria for identifying such alternatives and passenger segments which could potentially benefit from them, assessing efficacy of the alternative service with respect to traditional bus shuttles, estimating operational requirements, and evaluating the mitigation benefit of an alternative. The implementation of the framework has been demonstrated for three case studies of recent shutdowns in the MBTA, using data sources available at the agency. Post-implementation evaluation of potential alternatives to shuttle service in two of these case studies shows substantial potential magnitudes of passenger benefit and proportion of passenger impact being mitigated.by Mihir Ravindra Bhosale.S.M. in TransportationS.M.inTransportation Massachusetts Institute of Technology, Department of Urban Studies and Plannin
Earthquake vulnerability assessment of buildings of ward no. 8 of Haldwani–Kathgodam Municipal Corporation, Uttarakhand, India
No full textHigh Concentration of an ISS-N1-Targeting Antisense Oligonucleotide Causes Massive Perturbation of the Transcriptome
Get PDFIntronic splicing silencer N1 (ISS-N1) located within Survival Motor Neuron 2 (SMN2) intron 7 is the target of a therapeutic antisense oligonucleotide (ASO), nusinersen (Spinraza), which is currently being used for the treatment of spinal muscular atrophy (SMA), a leading genetic disease associated with infant mortality. The discovery of ISS-N1 as a promising therapeutic target was enabled in part by Anti-N1, a 20-mer ASO that restored SMN2 exon 7 inclusion by annealing to ISS-N1. Here, we analyzed the transcriptome of SMA patient cells treated with 100 nM of Anti-N1 for 30 h. Such concentrations are routinely used to demonstrate the efficacy of an ASO. While 100 nM of Anti-N1 substantially stimulated SMN2 exon 7 inclusion, it also caused massive perturbations in the transcriptome and triggered widespread aberrant splicing, affecting expression of essential genes associated with multiple cellular processes such as transcription, splicing, translation, cell signaling, cell cycle, macromolecular trafficking, cytoskeletal dynamics, and innate immunity. We validated our findings with quantitative and semiquantitative PCR of 39 candidate genes associated with diverse pathways. We also showed a substantial reduction in off-target effects with shorter ISS-N1-targeting ASOs. Our findings are significant for implementing better ASO design and dosing regimens of ASO-based drugs.This article is published as Ottesen, Eric William, Diou Luo, Natalia Nikolaevna Singh, and Ravindra Narayan Singh. "High concentration of an iss-n1-targeting antisense oligonucleotide causes massive perturbation of the transcriptome." International journal of molecular sciences 22, no. 16 (2021): 8378.
DOI: 10.3390/ijms22168378.
Copyright 2021 The Author(s).
Attribution 4.0 International (CC BY 4.0).
Posted with permission
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