473 research outputs found
Ariel - Volume 11 Number 3
Executive Editors
Ellen Feldman
Leonardo S. Nasca, Jr.
Business Managers
Barbara L. Davies
Martin B. Getzow
News Editor
Hugh A. Gelabert
Features Editor
Aaron D. Bleznak
CAHS Editor
Joan M. Greco
Editorial Page Editor
Samuel Markind
Photography Editor
Todd Demmy
Sports Editor
Paul F. Mansfiel
Ariel - Volume 11 Number 2
Executive Editors
Ellen Feldman
Leonardo S. Nasca, Jr.
Business .Managers
Barbara L. Davies
Martin B. Getzow
News Editor
Aaron D. Bleznak
Features Editor
Hugh A. Gelabert
CAHS Editor
Joan M. Greco
Editorial Page Editor
Samuel Markind
Photography Editor
Leonardo S. Nasca, Jr.
Sports Editor
Paul F. Mansfiel
Ariel - Volume 11 Number 1
Executive Editors
Ellen Feldman
Leonardo S. Nasca, Jr.
Business Managers
Barbara L. Davies
Martin B. Getzow
News Editor
Aaron D. Bleznak
Features Editor
Dave Van Wagoner
CAHS Editor
Joan M. Greco
Editorial Page Editor
Samuel Markind
Photography Editor
Leonardo S. Nasca, Jr.
Sports Editor
Paul F. Mansfiel
Validation of a Multivariate Serum Profile for Epithelial Ovarian Cancer Using a Prospective Multi-Site Collection
In previous studies we described the use of a retrospective collection of ovarian cancer and benign disease samples, in combination with a large set of multiplexed immunoassays and a multivariate pattern recognition algorithm, to develop an 11-biomarker classification profile that is predictive for the presence of epithelial ovarian cancer. In this study, customized, Luminex-based multiplexed immunoassay kits were GMP-manufactured and the classification profile was refined from 11 to 8 biomarkers (CA-125, epidermal growth factor receptor, CA 19-9, C-reactive protein, tenascin C, apolipoprotein AI, apolipoprotein CIII, and myoglobin). The customized kits and the 8-biomarker profile were then validated in a double-blinded manner using prospective samples collected from women scheduled for surgery, with a gynecologic oncologist, for suspicion of having ovarian cancer. The performance observed in model development held in validation, demonstrating 81.1% sensitivity (95% CI 72.6 – 87.9%) for invasive epithelial ovarian cancer and 85.4% specificity (95% CI 81.1 – 88.9%) for benign ovarian conditions. The specificity for normal healthy women was 95.6% (95% CI 83.6 – 99.2%). These results have encouraged us to undertake a second validation study arm, currently in progress, to examine the performance of the 8-biomarker profile on the population of women not under the surgical care of a gynecologic oncologist
Eupatilin Improves Cilia Defects in Human CEP290 Ciliopathy Models
The photoreceptor outer segment is a highly specialized primary cilium that is essential for phototransduction and vision. Biallelic pathogenic variants in the cilia-associated gene CEP290 cause non-syndromic Leber congenital amaurosis 10 (LCA10) and syndromic diseases, where the retina is also affected. While RNA antisense oligonucleotides and gene editing are potential treatment options for the common deep intronic variant c.2991+1655A>G in CEP290, there is a need for variant-independent approaches that could be applied to a broader spectrum of ciliopathies. Here, we generated several distinct human models of CEP290-related retinal disease and investigated the effects of the flavonoid eupatilin as a potential treatment. Eupatilin improved cilium formation and length in CEP290 LCA10 patient-derived fibroblasts, in gene-edited CEP290 knockout (CEP290 KO) RPE1 cells, and in both CEP290 LCA10 and CEP290 KO iPSCs-derived retinal organoids. Furthermore, eupatilin reduced rhodopsin retention in the outer nuclear layer of CEP290 LCA10 retinal organoids. Eupatilin altered gene transcription in retinal organoids by modulating the expression of rhodopsin and by targeting cilia and synaptic plasticity pathways. This work sheds light on the mechanism of action of eupatilin and supports its potential as a variant-independent approach for CEP290-associated ciliopathies
Influence of a knot on the strength of a polymer strand
Many experiments have been done to determine the relative strength of
different knots, and these show that the break in a knotted rope almost
invariably occurs at a point just outside the `entrance' to the knot. The
influence of knots on the properties of polymers has become of great interest,
in part because of their effect on mechanical properties. Knot theory applied
to the topology of macromolecules indicates that the simple trefoil or
`overhand' knot is likely to be present with high probability in any long
polymer strand. Fragments of DNA have been observed to contain such knots in
experiments and computer simulations. Here we use {\it ab initio} computational
methods to investigate the effect of a trefoil knot on the breaking strength of
a polymer strand. We find that the knot weakens the strand significantly, and
that, like a knotted rope, it breaks under tension at the entrance to the knot.Comment: 3 pages, 4 figure
Tightness of slip-linked polymer chains
We study the interplay between entropy and topological constraints for a
polymer chain in which sliding rings (slip-links) enforce pair contacts between
monomers. These slip-links divide a closed ring polymer into a number of
sub-loops which can exchange length between each other. In the ideal chain
limit, we find the joint probability density function for the sizes of segments
within such a slip-linked polymer chain (paraknot). A particular segment is
tight (small in size) or loose (of the order of the overall size of the
paraknot) depending on both the number of slip-links it incorporates and its
competition with other segments. When self-avoiding interactions are included,
scaling arguments can be used to predict the statistics of segment sizes for
certain paraknot configurations.Comment: 10 pages, 6 figures, REVTeX
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