661 research outputs found

    Design and fabrication of a system for the additive manufacturing of transparent glass

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    Despite glass\u27 prevalence in the scientific and engineering community, very little research has been conducted attempting to additively manufacture (AM) glass. Even less research has been done on optically transparent glass. Glass’ material properties make it ineligible for most AM processes if the end result is to be transparent. Even small gas inclusions can cause large amounts of scattering. Additively manufacturing transparent glass brings the advantages found in other AM processes with the added benefit of having optical properties better than those found in polymers. Additively manufacturing glass also allows the optical properties of transparent parts to vary arbitrarily. This thesis presents the design, manufacture, and control of a system to AM transparent glass. The system feeds glass wires, which are opaque in the near infrared, into a melt pool maintained by a CO₂ laser (10.6μm). The laser beam and melt pool remained fixed as the AM part is moved using a motion stage as the glass is deposited layer-by-layer. The stages are controlled using a PID controller, and the wire feeders are controlled using a PD controller. A spring damper model is also presented to model the deposition process along the feed direction, and perpendicular to the feed direction for control purposes. The Glass AM process is able to create morphologically accurate glass pieces more efficiently, and with fewer filament breakages than the prototype system. The glass produced with this system has optical properties as good as cast glass. The Glass AM system is also expandable and interchangeable so that more subsystems can be added and changed with minimal redesign --Abstract, page iii

    Advancement in maritime technology and its impact on safety

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    This paper is entitled Advancement in Maritime Technology and its impact on safety . In 1964 Diebold stated THE EFFECTS OF THE TECHNICAL REVOLUTION WE ARE NOW LIVING THROUGH WILL BE DEEPER THAN ANY SOCIAL CHANGE WE HAVE EXPERIENCED BEFORE “ It is twenty three years now since Diebold gave the statement and he surely could not be more right if a close look is conducted on what is happening today. This paper is written with the aim of bringing to the people\u27s awareness,the current level of advanced maritime technology and its impact on safety. The methodology used has been collection of data from books, international and national organizations and firms through correspondence, proceedings from seminars, lectures given in class, individuals, colleagues, etc. This data was then processed and compiled to form the paper. The paper starts with an overview of the different transportation modes before going into the maritime industry. The paper covers a wide range of the maritime industry but emphasis is given to what is happening at sea especially in the nautical field where the author spent thirteen years of his working life before embarking into teaching. Effects of advanced maritime technology towards safety are covered throughout the paper and examples have been given where more emphasis was deemed necessary. The paper is slightly technical but very much within the scope of understanding of many people connected with the shipping industry. The paper winds up with the following recommendations:- 1. Shipping should be given due consideration in all countries. 2. Governments should continue delegating responsibilities to non- government institutions where it is in the interest of all parties. 3. Technology based training should be used where appropriate. 4. The implications of purchasing highly sophisticated second hand vessels should be considered before doing it. 5. Technology must be allowed to advance. 6. A deep desire to prevent accidents must be cultivated to ail people involved with maritime affairs

    Chemotherapeutic Resistance: Surviving Stressful Situations

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    Chemotherapeutic regimens involve the systemic administration of genotoxic compounds that induce cancer cell death via well-established DNA damage response signaling networks. Less understood is how the treatment of other cell types within the tumor microenvironment affects the therapeutic response. Here we discuss recent work that shows that tumor-adjacent cells can respond to genotoxic stress by activating a paracrine secretory program. Although this secretory response serves to protect progenitor cells and promote tissue regeneration in conditions of cellular stress, it can also be coopted by tumor cells to survive frontline chemotherapy. Thus, local prosurvival signaling may present a fundamental barrier to tumor clearance by genotoxic agents, suggesting that effective treatments need to target both cancer cells and the tumor microenvironment. Cancer Res; 71(15); 5062–6.National Institutes of Health (U.S.) (RO1 CA128803)Massachusetts Institute of Technology. Ludwig Center for Molecular Oncology (Ludwig Graduate Fellowship

    Context-specific roles for paracrine IL-6 in lymphomagenesis

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    A basic requirement for the development of complex organ systems is that the cellular response to identical environmental cues can vary significantly between distinct cell types and developmental stages. While it is well established that paracrine signaling can similarly elicit diverse responses in distinct tumor types, the relevance of developmental stage-specific signaling responses to tumor development remains unclear. Here, we show that the same microenvironmental factor, IL-6, can both promote and prevent lymphoma development by acting on cells at distinct stages of hematopoietic development. Specifically, paracrine IL-6 signaling promotes the survival of transplanted hematopoietic stem cells following lethal irradiation, allowing for the persistence and expansion of progenitor cells bearing a cancer-promoting alteration. Conversely, IL-6 signaling also initiates a paracrine secretory program in the bone marrow that promotes B-cell differentiation and inhibits the development of B-cell malignancies. Thus, stage-specific responses to cytokines may promote progenitor cell expansion while also inhibiting neoplastic development within a single developmental lineage. Once transformed, the resulting B-cell lymphomas again use paracrine IL-6 signaling as a survival signal, highlighting the ability of tumor cells to co-opt pathways used for stem cell protection. These data not only suggest a complex regulation of tumor development by the preneoplastic microenvironment, but also that this regulation can decisively impact the outcome of well-established tumor modeling approaches.National Institutes of Health (U.S.) (RO1 CA128803)Massachusetts Institute of Technology. Ludwig Center for Molecular OncologyVirginia and Daniel K. Ludwig Graduate Fellowshi

    DNA Damage-Mediated Induction of a Chemoresistant Niche

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    While numerous cell-intrinsic processes are known to play decisive roles in chemotherapeutic response, relatively little is known about the impact of the tumor microenvironment on therapeutic outcome. Here, we use a well-established mouse model of Burkitt's lymphoma to show that paracrine factors in the tumor microenvironment modulate lymphoma cell survival following the administration of genotoxic chemotherapy. Specifically, IL-6 and Timp-1 are released in the thymus in response to DNA damage, creating a “chemo-resistant niche” that promotes the survival of a minimal residual tumor burden and serves as a reservoir for eventual tumor relapse. Notably, IL-6 is released acutely from thymic endothelial cells in a p38-dependent manner following genotoxic stress, and this acute secretory response precedes the gradual induction of senescence in tumor-associated stromal cells. Thus, conventional chemotherapies can induce tumor regression while simultaneously eliciting stress responses that protect subsets of tumor cells in select anatomical locations from drug action.National Institutes of Health (U.S.) (NIH RO1 CA128803)David H. Koch Institute for Integrative Cancer Research at MIT (Ludwig Center for Molecular Oncology))Massachusetts Institute of Technology. Department of Biology (Rita Allen Fellow

    Students’ Reactions to Reform Mathematics Pedagogy in a Postsecondary Remedial Mathematics Course

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    The students in this study were enrolled in a remedial mathematics course at a small 4-year university and were taught according to the reform pedagogical principles advocated by NCTM, AMATYC, and MAA. Since most of the students had not been previously exposed to these teaching methods, this study obtained students’ reactions (n = 22) to the course through an anonymous, free-response (not multiple choice) survey at the end of the course. Surveys from students in two equivalent “traditional” lecture courses (n = 44) were also analyzed and served as a baseline by which to gauge students’ responses from the reform group. The surveys asked for general likes and dislikes regarding the pedagogical practices that were employed in their respective courses. The findings from the surveys were that students in the reform course generally liked its key features (group work, student presentations, and graphing calculators), but roughly half of the class wished that the instructor spent more time doing many more example problems on the board as opposed to giving the class time to explore the mathematical principles underlying the example problems. Teachers who wish to use reform pedagogical practices need to be aware of student expectations as they plan their lessons

    Primary Hydatidosis Of The Tibia: A Tricky Diagnosis

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    Primary hydatidosis of the tibia is a rare disease. In an endemic area, it should be considered in the differential diagnosis of a hypolucent osteolytic lesion on xray. If not properly managed, anaphylactic shock may occur intraoperatively, as well as increased reccurence of the disease. This is a case report of a primary tibial hydatid cyst, treated first with curettage and phenolizaton, and then after recurrence, treated with total knee arthroplasty. We will review the literature of diagnosis and treatment of a hydatid cyst of the tibia

    Versatile in vivo regulation of tumor phenotypes by dCas9-mediated transcriptional perturbation

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    Targeted transcriptional regulation is a powerful tool to study genetic mediators of cellular behavior. Here, we show that catalytically dead Cas9 (dCas9) targeted to genomic regions upstream or downstream of the transcription start site allows for specific and sustainable gene-expression level alterations in tumor cells in vitro and in syngeneic immune-competent mouse models. We used this approach for a high-coverage pooled gene-activation screen in vivo and discovered previously unidentified modulators of tumor growth and therapeutic response. Moreover, by using dCas9 linked to an activation domain, we can either enhance or suppress target gene expression simply by changing the genetic location of dCas9 binding relative to the transcription start site. We demonstrate that these directed changes in gene-transcription levels occur with minimal off-target effects. Our findings highlight the use of dCas9-mediated transcriptional regulation as a versatile tool to reproducibly interrogate tumor phenotypes in vivo. Keywords: cancer genetics; cancer models; cancer therapeutic resistance; gene regulation; CRISPRNational Cancer Institute (U.S.) (Grant U54-CA112967-06)National Cancer Institute (U.S.) (Grant P30-CA14051

    What is primary eye health care?

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    BCL-2 family genetic profiling reveals microenvironment-specific determinants of chemotherapeutic response

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    The Bcl-2 family encompasses a diverse set of apoptotic regulators that are dynamically activated in response to various cell-intrinsic and -extrinsic stimuli. An extensive variety of cell culture experiments have identified effects of growth factors, cytokines, and drugs on Bcl-2 family functions, but in vivo studies have tended to focus on the role of one or two particular members in development and organ homeostasis. Thus, the ability of physiologically relevant contexts to modulate canonical dependencies that are likely to be more complex has yet to be investigated systematically. In this study, we report findings derived from a pool-based shRNA assay that systematically and comprehensively interrogated the functional dependence of leukemia and lymphoma cells upon various Bcl-2 family members across many diverse in vitro and in vivo settings. This approach permitted us to report the first in vivo loss of function screen for modifiers of the response to a front-line chemotherapeutic agent. Notably, our results reveal an unexpected role for the extrinsic death pathway as a tissue-specific modifier of therapeutic response. In particular, our findings show that particular tissue sites of tumor dissemination play critical roles in demarcating the nature and extent of cancer cell vulnerabilities and mechanisms of chemoresistance. Cancer Res; 71(17); 5850–8. ©2011 AACR.National Institutes of Health (U.S.) (NIH RO1 CA128803)National Cancer Institute (U.S.) (Integrated Cancer Biology Program grant NCI 1-U54-CA112967)David H. Koch Institute for Integrative Cancer Research at MIT (Ludwig Fellowship)Massachusetts Institute of Technology. Dept. of Biology (training grant
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