216 research outputs found
Quasicircles and bounded turning circles modulo bi-Lipschitz maps
30 pages, 3 figures, to appear in Rev. Mat. IberoamericanaWe construct a catalog, of snowflake type metric circles, that describes allmetric quasicircles up to \bl\ equivalence. This is a metric space analog of aresult due to Rohde. Our construction also works for all bounded turning metriccircles; these need not be doubling. As a byproduct, we show that a metricquasicircle with Assouad dimension strictly less than two is bi-Lipschitzequivalent to a planar quasicircle.Peer reviewe
Quasicircles and Bounded Turning Circles Modulo bi-Lipschitz Maps
We construct a catalog, of snowflake type metric circles, that describes all metric quasicircles up to \bl\ equivalence. This is a metric space analog of a result due to Rohde. Our construction also works for all bounded turning metric circles; these need not be doubling. As a byproduct, we show that a metric quasicircle with Assouad dimension strictly less than two is bi-Lipschitz equivalent to a planar quasicircle
Tumor site immune markers associated with risk for subsequent basal cell carcinomas.
BackgroundBasal cell carcinoma (BCC) tumors are the most common skin cancer and are highly immunogenic.ObjectiveThe goal of this study was to assess how immune-cell related gene expression in an initial BCC tumor biopsy was related to the appearance of subsequent BCC tumors.Materials and methodsLevels of mRNA for CD3Ξ΅ (a T-cell receptor marker), CD25 (the alpha chain of the interleukin (IL)-2 receptor expressed on activated T-cells and B-cells), CD68 (a marker for monocytes/macrophages), the cell surface glycoprotein intercellular adhesion molecule-1 (ICAM-1), the cytokine interferon-Ξ³ (IFN-Ξ³) and the anti-inflammatory cytokine IL-10 were measured in BCC tumor biopsies from 138 patients using real-time PCR.ResultsThe median follow-up was 26.6 months, and 61% of subjects were free of new BCCs two years post-initial biopsy. Patients with low CD3Ξ΅ CD25, CD68, and ICAM-1 mRNA levels had significantly shorter times before new tumors were detected (pβ=β0.03, pβ=β0.02, pβ=β0.003, and pβ=β0.08, respectively). Furthermore, older age diminished the association of mRNA levels with the appearance of subsequent tumors.ConclusionsOur results show that levels of CD3Ξ΅, CD25, CD68, and ICAM-1 mRNA in BCC biopsies may predict risk for new BCC tumors
OMNI: Open Mind Neuromodulation Interface for accelerated research and discovery
Electrical neuromodulation is an approved therapy for a number of neurologic disease states, including Parkinson's disease (PD), Obsessive Compulsive Disorder, Essential Tremor, epilepsy and neuropathic pain. Neuromodulatory strategies are also being piloted for an increasing number of additional indications, including Major Depressive Disorder, Dystonia, and addiction. The development of implantable devices capable of both neural sensing and adaptive stimulation may prove essential for both improving therapeutic outcomes and expanding the neuromodulation indication space. Nevertheless, an increasingly fragmented device ecosystem forces researchers and therapy developers to customize and reinvent data visualization, clinician engagement, and device control software to support individual clinical studies. Each hardware platform provides a unique software interface to the implanted neurostimulator, making pre-existing code from prior studies difficult to leverage for future work - a hindrance that will expand as device technology diversifies. Here, we envision, detail, and demonstrate the use of a novel software architecture, OMNI, that accelerates neuromodulation research by providing a flexible, platform- and device-agnostic interface for clinical research and therapy development
Comparative mitochondrial genomics of snakes: extraordinary substitution rate dynamics and functionality of the duplicate control region
<p>Abstract</p> <p>Background</p> <p>The mitochondrial genomes of snakes are characterized by an overall evolutionary rate that appears to be one of the most accelerated among vertebrates. They also possess other unusual features, including short tRNAs and other genes, and a duplicated control region that has been stably maintained since it originated more than 70 million years ago. Here, we provide a detailed analysis of evolutionary dynamics in snake mitochondrial genomes to better understand the basis of these extreme characteristics, and to explore the relationship between mitochondrial genome molecular evolution, genome architecture, and molecular function. We sequenced complete mitochondrial genomes from Slowinski's corn snake (<it>Pantherophis slowinskii</it>) and two cottonmouths (<it>Agkistrodon piscivorus</it>) to complement previously existing mitochondrial genomes, and to provide an improved comparative view of how genome architecture affects molecular evolution at contrasting levels of divergence.</p> <p>Results</p> <p>We present a Bayesian genetic approach that suggests that the duplicated control region can function as an additional origin of heavy strand replication. The two control regions also appear to have different intra-specific versus inter-specific evolutionary dynamics that may be associated with complex modes of concerted evolution. We find that different genomic regions have experienced substantial accelerated evolution along early branches in snakes, with different genes having experienced dramatic accelerations along specific branches. Some of these accelerations appear to coincide with, or subsequent to, the shortening of various mitochondrial genes and the duplication of the control region and flanking tRNAs.</p> <p>Conclusion</p> <p>Fluctuations in the strength and pattern of selection during snake evolution have had widely varying gene-specific effects on substitution rates, and these rate accelerations may have been functionally related to unusual changes in genomic architecture. The among-lineage and among-gene variation in rate dynamics observed in snakes is the most extreme thus far observed in animal genomes, and provides an important study system for further evaluating the biochemical and physiological basis of evolutionary pressures in vertebrate mitochondria.</p
Variations in Mesospheric Neutral Densities from Rayleigh Lidar Observations at Utah State University
A Rayleigh lidar was operated from 1993 to 2004, at the Atmospheric Lidar Observatory (ALO; 41.7Β°N, 111.8Β°W) at the Center for Atmospheric and Space Sciences (CASS) on the campus of Utah State University (USU). Observations were carried out on over 900 nights, 729 of which had good data starting at 45 km and going upward toward 90 km. They were reduced for absolute temperatures and relative neutral number densities. The latter at 45 km can be put on an absolute basis by using atmospheric models that go up to at least 45 km. The modelsβ absolute number densities at 45 km are used to normalize the lidar observations, thereby providing absolute densities from 45 to 90 km. We examine these absolute density profiles for differences from the overall mean density profile to show altitudinal structure and seasonal variations
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Fog2 is required for normal diaphragm and lung development in mice and humans
Congenital diaphragmatic hernia and other congenital diaphragmatic defects are associated with significant mortality and morbidity in neonates; however, the molecular basis of these developmental anomalies is unknown. In an analysis of E18.5 embryos derived from mice treated with N-ethyl-N-nitrosourea, we identified a mutation that causes pulmonary hypoplasia and abnormal diaphragmatic development. Fog2 (Zfpm2) maps within the recombinant interval carrying the N-ethyl-N-nitrosourea-induced mutation, and DNA sequencing of Fog2 identified a mutation in a splice donor site that generates an abnormal transcript encoding a truncated protein. Human autopsy cases with diaphragmatic defect and pulmonary hypoplasia were evaluated for mutations in FOG2. Sequence analysis revealed a de novo mutation resulting in a premature stop codon in a child who died on the first day of life secondary to severe bilateral pulmonary hypoplasia and an abnormally muscularized diaphragm. Using a phenotype-driven approach, we have established that Fog2 is required for normal diaphragm and lung development, a role that has not been previously appreciated. FOG2 is the first gene implicated in the pathogenesis of nonsyndromic human congenital diaphragmatic defects, and its necessity for pulmonary development validates the hypothesis that neonates with congenital diaphragmatic hernia may also have primary pulmonary developmental abnormalities
A Transient Transgenic RNAi Strategy for Rapid Characterization of Gene Function during Embryonic Development
RNA interference (RNAi) is a powerful strategy for studying the phenotypic consequences of reduced gene expression levels in model systems. To develop a method for the rapid characterization of the developmental consequences of gene dysregulation, we tested the use of RNAi for βtransient transgenicβ knockdown of mRNA in mouse embryos. These methods included lentiviral infection as well as transposition using the Sleeping Beauty (SB) and PiggyBac (PB) transposable element systems. This approach can be useful for phenotypic validation of putative mutant loci, as we demonstrate by confirming that knockdown of Prdm16 phenocopies the ENU-induced cleft palate (CP) mutant, csp1. This strategy is attractive as an alternative to gene targeting in embryonic stem cells, as it is simple and yields phenotypic information in a matter of weeks. Of the three methodologies tested, the PB transposon system produced high numbers of transgenic embryos with the expected phenotype, demonstrating its utility as a screening method
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