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Founded in 1970, the Harvard–MIT Division of Health science and Technology, or HST, is one of the oldest and largest biomedical engineering and physician-scientist training programs in the United States and the longest-standing functional collaboration between Harvard University and the Massachusetts Institute of Technology .HST's unique interdisciplinary educational program brings engineering as well as the physical and biological science from the scientist's bench to the patient's bedside. Conversely, it brings clinical insight from the patient's bedside to the laboratory bench. In this way, HST students are trained to have deep understanding of engineering, physical science, and the biological science, complemented with hands-on experience in the clinic or in industry; and they become conversant with the underlying quantitative and molecular aspects of medicine and biomedical science. Within the division, more than 400 graduate students work with eminent faculty and affiliated faculty members from throughout the MIT and Harvard communities. HST is also the home of the Laboratory of Computational Physiology which hosts the MIMIC II database and PhysioNet.In addition to its outstanding record of accomplishment for research in human health care, HST educational programs are distinguished by three key elements: A strong quantitative orientation Required hands-on experience in a clinical or industry setting A focused interdisciplinary research project↑ Wikipedia.

Qi H.,Harvard-MIT Division of Health Sciences and Technology
Nature communications | Year: 2013

Using DNA as programmable, sequence-specific 'glues', shape-controlled hydrogel units are self-assembled into prescribed structures. Here we report that aggregates are produced using hydrogel cubes with edge lengths ranging from 30 μm to 1 mm, demonstrating assembly across scales. In a simple one-pot agitation reaction, 25 dimers are constructed in parallel from 50 distinct hydrogel cube species, demonstrating highly multiplexed assembly. Using hydrogel cuboids displaying face-specific DNA glues, diverse structures are achieved in aqueous and in interfacial agitation systems. These include dimers, extended chains and open network structures in an aqueous system, and dimers, chains of fixed length, T-junctions and square shapes in the interfacial system, demonstrating the versatility of the assembly system. Source

Bourgeois F.T.,Childrens Hospital Boston | Murthy S.,University of Toronto | Mandl K.D.,Harvard-MIT Division of Health Sciences and Technology
Annals of Internal Medicine | Year: 2010

Background: Clinical trial registries are in widespread use to promote transparency around trials and their results. Objective: To describe characteristics of drug trials listed in ClinicalTrials. gov and examine whether the funding source of these trials is associated with favorable published outcomes. Design: An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006. Setting: ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999. Measurements: Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations. Results: Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization-funded trials (P < 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or nonfederal organization-funded trials without industry contributions (P = 0.005 across groups). Limitations: The publication status of a trial could not always be confirmed, which could result in misclassification. Additional information on study protocols and comprehensive trial results were not available to further explore underlying factors for the association between funding source and outcome reporting. Conclusion: In this sample of registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources. Primary Funding Source: National Library of Medicine and National Institute of Child Health and Human Development, National Institutes of Health. © 2010 American College of Physicians. Source

Kanasty R.,Massachusetts Institute of Technology | Dorkin J.R.,Massachusetts Institute of Technology | Vegas A.,Massachusetts Institute of Technology | Anderson D.,Massachusetts Institute of Technology | Anderson D.,Harvard-MIT Division of Health Sciences and Technology
Nature Materials | Year: 2013

RNA interference (RNAi) has broad potential as a therapeutic to reversibly silence any gene. To achieve the clinical potential of RNAi, delivery materials are required to transport short interfering RNA (siRNA) to the site of action in the cells of target tissues. This Review provides an introduction to the biological challenges that siRNA delivery materials aim to overcome, as well as a discussion of the way that the most effective and clinically advanced classes of siRNA delivery systems, including lipid nanoparticles and siRNA conjugates, are designed to surmount these challenges. The systems that we discuss are diverse in their approaches to the delivery problem, and provide valuable insight to guide the design of future siRNA delivery materials. © 2013 Macmillan Publishers Limited. All rights reserved. Source

Mirny L.A.,Harvard-MIT Division of Health Sciences and Technology
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Cooperative binding of transcription factors (TFs) to promoters and other regulatory regions is essential for precise gene expression. The classical model of cooperativity requires direct interactions between TFs, thus constraining the arrangement of TF sites in regulatory regions. Recent genomic and functional studies, however, demonstrate a great deal of flexibility in such arrangements with variable distances, numbers of sites, and identities of TF sites located in cis-regulatory regions. Such flexibility is inconsistent with cooperativity by direct interactions between TFs. Here, we demonstrate that strong cooperativity among noninteracting TFs can be achieved by their competition with nucleosomes. We find that the mechanism of nucleosome-mediated cooperativity is analogous to cooperativity in another multimolecular complex: hemoglobin. This surprising analogy provides deep insights, with parallels between the heterotropic regulation of hemoglobin (e.g., the Bohr effect) and the roles of nucleosome-positioning sequences and chromatin modifications in gene expression. Nucleosome-mediated cooperativity is consistent with several experimental studies, is equally applicable to repressors and activators, allows substantial flexibility in and modularity of regulatory regions, and provides a rationale for a broad range of genomic and evolutionary observations. Striking parallels between cooperativity in hemoglobin and in transcriptional regulation point to a general mechanism that can be used in various biological systems. Source

Greenberg S.A.,Harvard-MIT Division of Health Sciences and Technology
Muscle and Nerve | Year: 2014

Introduction: Recent studies have identified circulating immunoglobulin (Ig) G autoantibodies against cytoplasmic 5′-nucleotidase 1A (cN1A; NT5C1A) in patients with inclusion body myositis (IBM), whose detection provides for an IBM blood diagnostic test. Whether or not anti-cN1A autoantibody isotypes other than IgG are present in IBM has not previously been reported. Methods: Plasma and serum samples from 205 patients (50 with and155 without IBM) were studied for the presence of IgM and IgA, in addition to IgG, anti-cN1A autoantibodies using immunoblots and enzyme-linked immunoassays (ELISAs). Results: IgM, IgA, and IgG anti-cN1A autoantibodies were detected by ELISA with similar sensitivities (49-53%) and specificities (94-96%), but with differing patterns of autoantibody isotype presence. Combination assays of all 3 autoantibody levels improved diagnostic sensitivity to 76%. Conclusions: In addition to previously recognized IgG anti-cN1A autoantibodies, IBM patients have circulating IgM and IgA anti-cN1A autoantibodies. Differing patterns of these isotypes may be present and useful for diagnosis. © 2014 Wiley Periodicals, Inc. Source

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