153 research outputs found
Finite difference time domain modeling of spiral antennas
The objectives outlined in the original proposal for this project were to create a well-documented computer analysis model based on the finite-difference, time-domain (FDTD) method that would be capable of computing antenna impedance, far-zone radiation patterns, and radar cross-section (RCS). The ability to model a variety of penetrable materials in addition to conductors is also desired. The spiral antennas under study by this project meet these requirements since they are constructed of slots cut into conducting surfaces which are backed by dielectric materials
Excitatory and inhibitory amino acid binding sites in human dentate nucleus
Autoradiography of excitatory and inhibitory amino acid binding sites in human dentate nuclei indicated virtually no binding to N-methyl-d-aspartate (NMDA) or [gamma]-aminobutyric acidB (GABAB) binding sites, and a low density of kainate binding sites. [alpha]-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid, metabotropic-quisqualate, benzodiazepine, and [gamma]-aminobutyric acidA (GABAA) binding sites were present in moderate abundance. Our NMDA results differ from those found previously in rodents. GABAA receptors are probably the primary mediators of inhibitory neurotransmission and [alpha]-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and metabotropic-quisqualate receptors are probably the primary mediators of excitatory neurotransmission within the human deep cerebellar nuclei.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29126/1/0000165.pd
Large Anomalous Hall effect in a silicon-based magnetic semiconductor
Magnetic semiconductors are attracting high interest because of their
potential use for spintronics, a new technology which merges electronics and
manipulation of conduction electron spins. (GaMn)As and (GaMn)N have recently
emerged as the most popular materials for this new technology. While Curie
temperatures are rising towards room temperature, these materials can only be
fabricated in thin film form, are heavily defective, and are not obviously
compatible with Si. We show here that it is productive to consider transition
metal monosilicides as potential alternatives. In particular, we report the
discovery that the bulk metallic magnets derived from doping the narrow gap
insulator FeSi with Co share the very high anomalous Hall conductance of
(GaMn)As, while displaying Curie temperatures as high as 53 K. Our work opens
up a new arena for spintronics, involving a bulk material based only on
transition metals and Si, and which we have proven to display a variety of
large magnetic field effects on easily measured electrical properties.Comment: 19 pages with 5 figure
Patient engagement in designing, conducting, and disseminating clinical pain research : IMMPACT recommended considerations
The consensus recommendations are based on the views of IMMPACT meeting participants and do not necessarily represent the views of the organizations with which the authors are affiliated. The following individuals made important contributions to the IMMPACT meeting but were not able to participate in the preparation of this article: David Atkins, MD (Department of Veterans Affairs), Rebecca Baker, PhD (National Institutes of Health), Allan Basbaum, PhD (University of California San Francisco), Robyn Bent, RN, MS (Food and Drug Administration), Nathalie Bere, MPH (European Medicines Agency), Alysha Croker, PhD (Health Canada), Stephen Bruehl, PhD (Vanderbilt University), Michael Cobas Meyer, MD, MBS (Eli Lilly), Scott Evans, PhD (George Washington University), Gail Graham (University of Maryland), Jennifer Haythornthwaite, PhD (Johns Hopkins University), Sharon Hertz, MD (Hertz and Fields Consulting), Jonathan Jackson, PhD (Harvard Medical School), Mark Jensen, PhD (University of Washington), Francis Keefe, PhD (Duke University), Karim Khan, MD, PhD, MBA (Canadian Institutes of Health Research), Lynn Laidlaw (University of Aberdeen), Steven Lane (Patient-Centered Outcomes Research Institute), Karen Morales, BS (University of Maryland), David Leventhal, MBA (Pfizer), Jeremy Taylor, OBE (National Institute for Health Research), and Lena Sun, MD (Columbia University). The manuscript has not been submitted, presented, or published elsewhere. Parts of the manuscript have been presented in a topical workshop at IASP World Congress on Pain in Toronto, in 2022.Peer reviewedPublisher PD
Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations
In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination
Lessons learned from additional research analyses of unsolved clinical exome cases
BACKGROUND:
Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery.
METHODS:
We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent-offspring trios. Analyses performed on a research basis employed both WES from additional family members and complementary bioinformatics approaches and protocols.
RESULTS:
Analysis of all possible modes of Mendelian inheritance, focusing on both single nucleotide variants (SNV) and copy number variant (CNV) alleles, yielded a likely contributory variant in 36% (27/74) of cases. If one includes candidate genes with variants identified within a single family, a potential contributory variant was identified in a total of ~51% (38/74) of cases enrolled in this pilot study. The molecular diagnosis was achieved in 30/63 trios (47.6%). Besides this, the analysis workflow yielded evidence for pathogenic variants in disease-associated genes in 4/6 singleton cases (66.6%), 1/1 multiplex family involving three affected siblings, and 3/4 (75%) quartet families. Both the analytical pipeline and the collaborative efforts between the diagnostic and research laboratories provided insights that allowed recent disease gene discoveries (PURA, TANGO2, EMC1, GNB5, ATAD3A, and MIPEP) and increased the number of novel genes, defined in this study as genes identified in more than one family (DHX30 and EBF3).
CONCLUSION:
An efficient genomics pipeline in which clinical sequencing in a diagnostic laboratory is followed by the detailed reanalysis of unsolved cases in a research environment, supplemented with WES data from additional family members, and subject to adjuvant bioinformatics analyses including relaxed variant filtering parameters in informatics pipelines, can enhance the molecular diagnostic yield and provide mechanistic insights into Mendelian disorders. Implementing these approaches requires collaborative clinical molecular diagnostic and research efforts
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