Enhancement of L-Dopa Incorporation into Melanoma by Dopa Decarboxylase Inhibition

Melanoma cells possess a special biochemical pathway for the conversion of L-dopa to melanin. Selective incorporation of exogenous L-dopa into melanoma cells in vivo has been limited by extensive decarboxylation to dopamine. Pretreatment of animals bearing the S-91 Cloudman or ACI melanomas with Ro4-4602, a potent dopa decarboxylase inhibitor limited incorporation of label into adrenal tissue and enhanced entry of label into tumor. Six hours following pretreatment, the ratio of tumor to adrenal specific activities was altered from 0.25 to 1.5 for the S-91 melanoma and 0.68 to 1.99 for the ACI melanoma indicating diversion of metabolism away from catecholamine formation. The possibility of a selective diagnostic and/or therapeutic approach is proposed

Ice Regimes Encountered during the Transit of the USCGC Healy: 2 April to 25 April 2000.

This report presents a synopsis of the ice conditions encountered by the United States Coast Guard Cutter Healy during Phase III of the Ice Trials. Phase III was conducted from 31 March to 25 April 2000 in the in the Eastern Canadian Arctic. During that voyage, 118 Ice Regimes were traversed. This report includes a detailed description of 20 of those Ice Regimes. Particulars about the ice conditions, vessel routing, ship operations and climatic conditions are given. An Ice Numeral is calculated for each Ice Regime using the methodology outlined in the Arctic Ice Regime Shipping System (AIRSS) Regulations. A brief evaluation of AIRSS is given, whereby the calculated Ice Numeral is correlated with the relative ease or difficulty experienced by the Healy in each Regime.NRC publication: Ye

Axial Vibrations of Brass Wind Instrument Bells and Their Acoustical Influence: Theory and Simulations

Previous work has demonstrated that structural vibrations of brass wind instruments can audibly affect the radiated sound. Furthermore, these broadband effects are not explainable by assuming perfect coincidence of the frequency of elliptical structural modes with air column resonances. In this work a mechanism is proposed that has the potential to explain the broadband influences of structural vibrations on acoustical characteristics such as input impedance, transfer function, and radiated sound. The proposed mechanism involves the coupling of axial bell vibrations to the internal air column. The acoustical effects of such axial bell vibrations have been studied by extending an existing transmission line model to include the effects of a parasitic flow into vibrating walls, as well as distributed sound pressure sources due to periodic volume fluctuations in a duct with oscillating boundaries. The magnitude of these influences in typical trumpet bells, as well as in a complete instrument with an unbraced loop, has been studied theoretically. The model results in predictions of input impedance and acoustical transfer function differences that are approximately 1 dB for straight instruments and significantly higher when coiled tubes are involved or when very thin brass is used

Axial vibrations of brass wind instrument bells and their acoustical influence: Experiments

It has recently been proposed that the effects of structural vibrations on the radiated sound ofbrass wind instruments may be attributable to axial modes of vibration with mode shapes that contain no radial nodes [Kausel, Chatziioannou, Moore, Gorman, and Rokni, J. Acoust. Soc. Am.137, 3149–3162 (2015)]. Results of experiments are reported that support this theory. Mechanical measurements of a trumpet bell demonstrate that these axial modes do exist inbrass wind instruments. The quality factor of the mechanical resonances can be on the order of 10 or less, making them broad enough to encompass the frequency range of previously reported effects attributed to bell vibrations. Measurements of the input impedance show that damping bell vibrations can result in impedance changes of up to 5%, in agreement with theory.Measurements of the acoustic transfer function demonstrate that the axial vibrations couple to the internal sound field as proposed, resulting in changes in the transfer function of approximately 1 dB. In agreement with theory, a change in the sign of the effect is observed at the frequency of the structural resonance

An Integrated Oncology Data Warehouse for Clinical Decision Support and Complex Patient Cohort Identification in a Hybrid Cancer Center

BACKGROUND: A data warehouse is a repository that centralizes and integrates data from disparate systems to provide the ability to easily access historical, consistent data. Integration of disparate source systems into one centralized location can enable rapid identification of more robust research cohorts and enable data-driven decision making. The objective of the Miami Cancer Institute (MCI) Oncology Data Warehouse (ODW) is to collect and organize data from clinical records, research, and administrative systems to support information retrieval, business intelligence, and analytics for high-level decision making for oncology patients. The design, architecture, and implementation aligns with industry best practices which includes Data Governance, Enterprise Data Modeling, and Metadata Management. METHODS: We integrated structured and unstructured data from disparate sources into one centralized data model optimized for querying known as the ODW. The ODW is modeled as a star schema, with fact tables and conformed dimension tables, and expands to a galaxy schema with constellation facts and dimensions that can snowflake to other data models as needed. Each fact table represents a subject area (i.e. pathology), that is directly related to the conformed dimension tables using surrogate and foreign keys. Conformed dimensions represent the attributes associated to the subject area (i.e. date of encounter). The source data is extracted, transformed and loaded (ETL) automatically from different databases into a set of tables. The ETL code performs incremental loads at regular prescribed intervals into two parallel storage areas, a relational database management system (RDMS) as well as a Big Data file storage system. RESULTS: An interdisciplinary team of physicians, engineers, scientists, and subject matter experts at the Miami Cancer Institute of Baptist Health South Florida, has designed, developed, and implemented the ODW with information originating from different data sources which include: Electronic Medical Record (EMR) systems, Financial Systems, Clinical Trial Management Systems, Tumor Registries, Biospecimen Repositories, Pathology synoptic reports and archives, and Next Generation Sequencing services. Structurally it is a subject-oriented, integrated collection of data leveraging conformed dimensions. The ODW is capable of connecting most business intelligence (i.e. Tableau) or statistical (i.e. SAS) tools for automated or static report development. CONCLUSION: The growing ODW enables physicians, clinical management teams, and medical analysts to systematically mine and review the molecular, genomic, and associated clinical or administrative information of patients, and identify patterns that may influence treatment decisions and potential outcomes. By implementing an innovative combination of technology tools and methods, we were able to organize enterprise information about oncology patients which can be utilized for clinical decision support and precision medicine use cases

Buddy-to-Buddy, a citizen soldier peer support program to counteract stigma, PTSD, depression, and suicide

Citizen soldiers (National Guard and Reserves) represent approximately 40% of the two million armed forces deployed to Afghanistan and Iraq. Twenty-five to forty percent of them develop PTSD, clinical depression, sleep disturbances, or suicidal thoughts. Upon returning home, many encounter additional stresses and hurdles to obtaining care: specifically, many civilian communities lack military medical/psychiatric facilities; financial, job, home, and relationship stresses have evolved or have been exacerbated during deployment; uncertainty has increased related to future deployment; there is loss of contact with military peers; and there is reluctance to recognize and acknowledge mental health needs that interfere with treatment entry and adherence. Approximately half of those needing help are not receiving it. To address this constellation of issues, a private–public partnership was formed under the auspices of the Welcome Back Veterans Initiative. In Michigan, the Army National Guard teamed with the University of Michigan and Michigan State University to develop innovative peer-to-peer programs for soldiers (Buddy-to-Buddy) and augmented programs for military families. Goals are to improve treatment entry, adherence, clinical outcomes, and to reduce suicides. This manuscript describes training approaches, preliminary results, and explores future national dissemination.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79148/1/j.1749-6632.2010.05719.x.pd

Couples Coping Through Deployment: Findings From a Sample of National Guard Families

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140037/1/jclp22487.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140037/2/jclp22487_am.pd

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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)