1,071 research outputs found

    How the Demographic Composition of Academic Science and Engineering Departments Influences Workplace Culture, Faculty Experience, and Retention Risk

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    Although on average women are underrepresented in academic science, technology, engineering, and mathematics (STEM) departments at universities, an underappreciated fact is that women’s representation varies widely across STEM disciplines. Past research is fairly silent on how local variations in gender composition impact faculty experiences. This study fills that gap. A survey of STEM departments at a large research university finds that women faculty in STEM are less professionally satisfied than male colleagues only if they are housed in departments where women are a small numeric minority. Gender differences in satisfaction are largest in departments with less than 25% women, smaller in departments with 25–35% women, and nonexistent in departments approaching 50% women. Gender differences in professional satisfaction in gender-unbalanced departments are mediated by women’s perception that their department’s climate is uncollegial, faculty governance is non-transparent, and gender relations are inequitable. Unfavorable department climates also predict retention risk for women in departments with few women, but not in departments closer to gender parity. Finally, faculty who find within-department mentors to be useful are more likely to have a favorable view of their department’s climate, which consequently predicts more professional satisfaction. Faculty gender and gender composition does not moderate these findings, suggesting that mentoring is equally effective for all faculty

    A common founding clone with TP53 and PTEN mutations gives rise to a concurrent germ cell tumor and acute megakaryoblastic leukemia

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    We report the findings from a patient who presented with a concurrent mediastinal germ cell tumor (GCT) and acute myeloid leukemia (AML). Bone marrow pathology was consistent with a diagnosis of acute megakaryoblastic leukemia (AML M7), and biopsy of an anterior mediastinal mass was consistent with a nonseminomatous GCT. Prior studies have described associations between hematological malignancies, including AML M7 and nonseminomatous GCTs, and it was recently suggested that a common founding clone initiated both cancers. We performed enhanced exome sequencing on the GCT and the AML M7 from our patient to define the clonal relationship between the two cancers. We found that both samples contained somatic mutations in PTEN (C136R missense) and TP53 (R213 frameshift). The mutations in PTEN and TP53 were present at ∼100% variant allele frequency (VAF) in both tumors. In addition, we detected and validated five other shared somatic mutations. The copy-number analysis of the AML exome data revealed an amplification of Chromosome 12p. We also identified a heterozygous germline variant in FANCA (S858R), which is known to be associated with Fanconi anemia but is of uncertain significance here. In summary, our data not only support a common founding clone for these cancers but also suggest that a specific set of distinct genomic alterations (in PTEN and TP53) underlies the rare association between GCT and AML. This association is likely linked to the treatment resistance and extremely poor outcome of these patients. We cannot resolve the clonal evolution of these tumors given limitations of our data

    A case of acute myeloid leukemia with promyelocytic features characterized by expression of a novel RARG-CPSF6 fusion

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    Key Points Novel RARG-CPSF6 fusion in an AML case with promyelocytic features and no evidence of PML-RARA or X-RARA fusion. Gene fusions involving RARG can initiate AML with promyelocytic morphological features.</jats:p

    Injectable Self-Healing Glucose-Responsive Hydrogels with pH-Regulated Mechanical Properties

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    Dynamically restructuring pH-responsive hydrogels are synthesized, employing dynamic covalent chemistry between phenylboronic acid and cis-diol modified poly(ethylene glycol) macromonomers. These gels display shear-thinning behavior, followed by a rapid structural recovery (self-healing). Size-dependent in vitro controlled and glucose-responsive release of proteins from the hydrogel network, as well as the biocompatibility of the gels, are evaluated both in vitro and in vivo.Leona M. and Harry B. Helmsley Charitable Trust (Award 2014PG-T1D002)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award F32DK101335)Wellcome Trust-MIT Postdoctoral Fellowshi

    Telomere Recognition and Assembly Mechanism of Mammalian Shelterin

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    Shelterin is a six-subunit protein complex that plays crucial roles in telomere length regulation, protection, and maintenance. Although several shelterin subunits have been studied in vitro, the biochemical properties of the fully assembled shelterin complex are not well defined. Here, we characterize shelterin using ensemble biochemical methods, electron microscopy, and single-molecule imaging to determine how shelterin recognizes and assembles onto telomeric repeats. We show that shelterin complexes can exist in solution and primarily locate telomeric DNA through a three-dimensional diffusive search. Shelterin can diffuse along non-telomeric DNA but is impeded by nucleosomes, arguing against extensive one-dimensional diffusion as a viable assembly mechanism. Our work supports a model in which individual shelterin complexes rapidly bind to telomeric repeats as independent functional units, which do not alter the DNA-binding mode of neighboring complexes but, rather, occupy telomeric DNA in a "beads on a string" configuration

    A multimerizing transcription factor of sea urchin embryos capable of looping DNA

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    SpGCF1 is a recently cloned sea urchin transcription factor that recognizes target sites in several different sea urchin genes. We find that in gel-shift experiments this factor is able to multimerize. A quantitative simulation of the gel-shift results suggests that SpGCF1 molecules that are bound to DNA target sites may also bind to one another, thus associating several DNA probe molecules. SpGCF1 might therefore be able to loop DNA molecules bearing its target sites at distant locations. We demonstrate this prediction by electron microscopy, and using the well-characterized cis-regulatory domain of the CyIIIa cytoskeletal actin gene, we show that the loop conformations predicted from the known SpGCF1 target site locations are actually formed in vitro. We speculate that the multimerization of this factor in vivo may function to bring distant regions of extended regulatory domains into immediate proximity so that they can interact with one another

    Multi-Material Processing By Lens

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    During the past few years, solid freeform fabrication has evolved into direct fabrication of metallic components using computer aided design (CAD) solid models. [1-4] Laser Engineered Net Shaping (LENSâ„¢) is one such technique [5-7] being developed at Sandia to fabricate high strength, near net shape metallic components. In the past two years a variety of components have been fabricated using LENSâ„¢ for applications ranging from prototype parts to injection mold tooling. [8] To advance direct fabrication capabilities, a process must be able to accommodate a wide range ofmaterials, including alloys and composites. This is important for tailoring certain physical properties critical to component performance. Examples include graded deposition for matching coefficient ofthermal expansion between dissimilar materials, layered fabrication for novel mechanical properties, and new alloy design where elemental constituents and/or alloys are blended to create new materials. In this paper, we will discuss the development ofprecise powder feeding capabilities for the LENSTM process to fabricate graded or layered material parts. We also present preliminary results from chemical and microstructural analysis.Mechanical Engineerin
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