A Compact Fiber Optic Eye Diagnostic System

A new fiber optic probe developed for determining transport properties of sub-micron particles in fluid experiments in a microgravity environment has been applied to study different parts of an eye. The probe positioned in front of an eye, delivers a low power (approximately few microW) light from a laser diode into the eye and guides the light which is back scattered by different components (aqueous humor, lens, and vitreous humor) of the eye through a receiving optical fiber to a photo detector. The probe provides rapid determination of macromolecular diffusivities and their respective size distributions in the eye lens and the gel-like materials in the vitreous humor. In a clinical setting, the probe can be mounted on a standard slit-lamp apparatus simply using a Hruby lens holder. The capability of detecting cataracts, both nuclear and cortical, in their early stages of formation, in a non invasive and quantitative fashion, has the potential in patient monitoring and in developing and testing new drugs or diet therapies to 'dissolve' or slow down the cataract formation before the surgery becomes necessary. The ability to detect biochemical and macromolecular changes in the vitreous structure can be very useful in identifying certain diseases of the posterior chamber and their complications, e.g., posterior vitreous detachment and diabetic retinopathy

A Compact Fiber Optic Eye Diagnostics System

A new fiber optic probe development for determining transport properties of sub-micron particles in fluids experiments in a microgravity environment has been applied to study different parts of the eye. The probe positioned in front of an eye, delivers a low power (approximately a few mu W) light from a laser diode into the eye and guides the light which is back scattered by different components (aqueous humor, lens, and vitreous humor) of the eye through a receiving optical fiber to a photo detector. The probe provides rapid determination of macromolecular diffusivities and their respective size distributions in the eye lens and the gel-like material in the vitreous humor. For a clinical use, the probe is mounted on a standard slit-lamp apparatus simply using Hruby lens holder. The capability of detecting cataracts, both nuclear and cortical, in their early stages of formation, in a non invasive and quantitative fashion, has the potential in patient monitoring and in developing and testing new drugs or diet therapies to 'dissolve' or slow down the cataract formation before the surgery becomes necessary. The ability to detect biochemical and macromolecular changes in the vitreous structure can be very useful in identifying certain diseases of the posterior chamber and their complications, e.g., posterior vitreous detachment and diabetic retinopathy

Ph-positive CML in blastic phase with monosomy 7 in a Down syndrome patient. Monitoring by interphase cytogenetics and demonstration of maternal allelic loss

We report a case of Ph-positive chronic myelocytic leukemia in blastic phase in an 11-year-old boy with Down syndrome. Monosomy 7 was the only additional chromosomal anomaly in the blastic clone. Fluorescence in situ hybridization analysis on interphase nuclei with a centromeric probe specific to chromosome 7 proved to be efficient in disease monitoring; and showed, together with the results of chromosome analysis on metaphases, that B- lymphocytes at the origin of an EBV-established line were not part of the leukemic clone. The study of DNA polymorphisms showed that the origin of the constitutional trisomy 21 was a maternal anaphase I nondisjunction, that the chromosome 7 lost in the blastic marrow clone was the maternal one, and led us to postulate that the mother's chromosomes are prone to impairment of normal disjunction. The study of allelic losses of chromosome 7 loci proved to be a further possibility for disease monitoring

Constitutional trisomy 8 as first mutation in multistep carcinogenesis: clinical, cytogenetic, and molecular data on three cases.

Three patients, with constitutional trisomy 8 mosaicism (CT8M), who developed a malignancy are reported. The diagnoses were refractory anaemia, acute lymphoblastic leukaemia, and idiopathic myelofibrosis. In the child with acute leukaemia, the CT8M was diagnosed at birth due to severe dysmorphisms and malformations; the other two patients showed a milder phenotype, and the CT8M was diagnosed only after the finding of trisomy 8 in neoplastic cells. The review of eight similar, previously reported cases and the clinical, cytogenetic, and molecular studies performed in our patients led us to make the following observations: (1) CT8M predisposes to neoplasms, preferentially to myelo- or lymphoproliferative diseases; (2) a gene dosage effect for glutathione reductase in red blood cells was seen in two of our patients; (3) the wide phenotypic variation of CT8M was confirmed: trisomy 8 in neoplastic cells of phenotypically near-normal cases may be misinterpreted as acquired; and (4) molecular studies suggested a postzygotic origin of the trisomy in our three cases, with the supernumerary chromosome being of paternal origin in one case and of maternal origin in the other two. We postulate that the trisomy 8 in neoplasms may often occur by mitotic nondisjunction in an early embryonic multipotent cell and that what is usually interpreted as an acquired trisomy 8 may in fact be CT8M. The constitutional trisomy 8 would act as a pathogenetically important first mutation in multistep carcinogenesis. Whenever trisomy 8 is found in malignancies, the patient should be reevaluated clinically to exclude CT8M, and CT8M patients should be monitored for the possible development of malignancies

Real-time single-molecule imaging reveals a direct interaction between UvrC and UvrB on DNA tightropes

Nucleotide excision DNA repair is mechanistically conserved across all kingdoms of life. In prokaryotes, this multi-enzyme process requires six proteins: UvrA?D, DNA polymerase I and DNA ligase. To examine how UvrC locates the UvrB? DNA pre-incision complex at a site of damage, we have labeled UvrB and UvrC with different colored quantum dots and quantitatively observed their interactions with DNA tightropes under a variety of solution conditions using oblique angle fluorescence imaging. Alone, UvrC predominantly interacts statically with DNA at low salt. Surprisingly, however, UvrC and UvrB together in solution bind to form the previously unseen UvrBC complex on duplex DNA. This UvrBC complex is highly motile and engages in unbiased one-dimensional diffusion. To test whether UvrB makes direct contact with the DNA in the UvrBC?DNA complex, we investigated three UvrB mutants: Y96A, a b-hairpin deletion and D338N. These mutants affected the motile properties of the UvrBC complex, indicating that UvrB is in intimate contact with the DNA when bound to UvrC. Given the in vivo excess of UvrB and the abundance of UvrBC in our experiments, this newly identified complex is likely to be the predominant form of UvrC in the cell. © 2013 The Author(s)

Crystal structure of the UvrB dimer: insights into the nature and functioning of the UvrAB damage engagement and UvrB-DNA complexes

UvrB has a central role in the highly conserved UvrABC pathway functioning not only as a damage recognition element but also as an essential component of the lesion tracking machinery. While it has been recently confirmed that the tracking assembly comprises a UvrA2B2 heterotetramer, the configurations of the damage engagement and UvrB-DNA handover complexes remain obscure. Here, we present the first crystal structure of a UvrB dimer whose biological significance has been verified using both chemical cross-linking and electron paramagnetic resonance spectroscopy. We demonstrate that this dimeric species stably associates with UvrA and forms a UvrA2B2-DNA complex. Our studies also illustrate how signals are transduced between the ATP and DNA binding sites to generate the helicase activity pivotal to handover and formation of the UvrB2-DNA complex, providing key insights into the configurations of these important repair intermediates

Navigating Open-Ended Spaces: Writing, Representing, and Speaking in a Fifth-Grade Science and Engineering Unit

Recent reforms in elementary science and engineering standards present intriguing new opportunities for the development of project-based interdisciplinary curricula. Although project-based learning has a long research tradition, the field could benefit from more observations and analyses of classroom-level lesson enactments to provide support for the notion that a project-based integrated science and engineering unit may provide a fertile context for students to be supported to engage in sense-making and communicate their thinking through disciplinary literacy practices that are novel to elementary instruction. Therefore, I studied the enactment of a fifth-grade unit on Polynesian wayfinding that I developed in collaboration with my advisor. I collected the data for this study during 2019-20 in a single classroom at a public school in the Midwest. This dissertation is comprised of two manuscripts that explore different aspects of the project-based integrated unit. In the first study, I explored the practice of scientific modeling and how students, with the support of peer feedback, transformed observations of a physical investigation into a drawn/written model. Through a conceptual analysis of student artifacts, classroom videos and field notes, and student interviews, I constructed explanations of students’ sense-making, and changes in their thinking, while engaged in the practice of modeling and peer review. The findings highlight that students created models that addressed spatial, temporal, and conceptual features of the phenomenon. Even as novice writer-designers, students used sophisticated techniques like multiple views and multiple timepoints. Students included invisible elements, such as evaporation and heat transfer, but they were not always successful in making clear connections among the components. Students improved the accuracy and completeness of their models by engaging in a one-on-one feedback process using a structured protocol. Findings from this study indicate that modeling, especially when supported by peer feedback, is an interdisciplinary practice wherein elementary students can bring to bear written and drawn elements to communicate sophisticated ideas in science. In the second study, I explored the practice of engineering design and how students used drawn/written plans to create physical models. Through a careful review of recordings from multiple cameras, supplemented with student artifacts, interviews, and surveys, I analyzed the enactment of a project to plan, build, and test physical models of long-distance voyaging canoes. The findings highlight that the use of a written design planner with embedded guiding questions supported students with many aspects of design, including discussing and providing reasoning for decisions about materials. Working with university mentors allowed students to receive focused attention from adults with specific disciplinary knowledge. Findings from this study indicate that the use of written design planners and the participation of university mentors supported students in successfully constructing canoe models and in deepening their conceptual understandings of the physics concepts related to sailing. Together, these studies provide illustrative examples of disciplinary literacy within the enactment of a fifth-grade project-based science and engineering unit. The findings add to existing research focused on the science practice of the development and use of models, and the engineering practice of design, at the elementary level. Overall, these studies offer ideas and inspiration for future educators, researchers, and curriculum designers.PhDEducational StudiesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169716/1/dellaveg_1.pd