LARGE PARTICLES IN ACTIVE ASTEROID P/2010 A2

Jewitt, David,Ishiguro, Masateru,Agarwal, Jessica IOP Publishing 2013 ASTROPHYSICAL JOURNAL LETTERS - Vol.764 No.1

<P>The previously unknown asteroid P/2010 A2 rose to prominence in 2010 by forming a transient, comet-like tail consisting of ejected dust. The observed dust production was interpreted as the result of either a hypervelocity impact with a smaller body or a rotational disruption. We have re-observed this object, finding that large particles remain a full orbital period after the initial outburst. In the intervening years, particles smaller than similar to 3 mm in radius have been dispersed by radiation pressure, leaving only larger particles in the trail. Since the total mass is dominated by the largest particles, the radiation pressure filtering allows us to obtain a more reliable estimate of the debris mass than was previously possible. We find that the mass contained in the debris is similar to 5 x 10(8) kg (assumed density 3000 kg m(-3)), the ratio of the total debris mass to the nucleus mass is similar to 0.1, and that events like P/2010 A2 contribute <3% to the Zodiacal dust production rate. Physical properties of the nucleus and debris are also determined.</P>

FRAGMENTATION KINEMATICS IN COMET 332P/IKEYA-MURAKAMI

Jewitt, David,Mutchler, Max,Weaver, Harold,Hui, Man-To,Agarwal, Jessica,Ishiguro, Masateru,Kleyna, Jan,Li, Jing,Meech, Karen,Micheli, Marco,Wainscoat, Richard,Weryk, Robert American Astronomical Society 2016 ASTROPHYSICAL JOURNAL LETTERS - Vol.829 No.1

<P>We present initial time-resolved observations of the split comet 332P/Ikeya-Murakami taken using the Hubble Space Telescope. Our images reveal a dust-bathed cluster of fragments receding from their parent nucleus at projected speeds in the range 0.06-3.5 m s(-1) from which we estimate ejection times from 2015 October to December. The number of fragments with effective radii greater than or similar to 20 m follows a differential power law with index gamma = -3.6 +/- 0.6, while smaller fragments are less abundant than expected from an extrapolation of this power law. We argue that, in addition to losses due to observational selection, torques from anisotropic outgassing are capable of destroying the small fragments by driving them quickly to rotational instability. Specifically, the spin-up times of fragments. 20 m in radius are shorter than the time elapsed since ejection from the parent nucleus. The effective radius of the parent nucleus is re <= 275 m (geometric albedo 0.04 assumed). This is about seven times smaller than previous estimates and results in a nucleus mass at least 300 times smaller than previously thought. The mass in solid pieces, 2 x 10(9) kg, is about 4% of the mass of the parent nucleus. As a result of its small size, the parent nucleus also has a short spin-up time. Brightness variations in time-resolved nucleus photometry are consistent with rotational instability playing a role in the release of fragments.</P>

HUBBLE SPACE TELESCOPE INVESTIGATION OF MAIN-BELT COMET 133P/ELST-PIZARRO

Jewitt, David,Ishiguro, Masateru,Weaver, Harold,Agarwal, Jessica,Mutchler, Max,Larson, Steven American Institute of Physics 2014 The Astronomical journal Vol.147 No.5

<P>We report new observations of the prototype main-belt comet (active asteroid) 133P/Elst-Pizarro taken at high angular resolution using the Hubble Space Telescope. The object has three main components: (1) a point-like nucleus; (2) a long, narrow antisolar dust tail; and (3) a short, sunward anti-tail. There is no resolved coma. The nucleus has a mean absolute magnitude H<SUB>V</SUB> = 15.70 ± 0.10 and a light curve range ΔV = 0.42 mag, the latter corresponding to projected dimensions 3.6 × 5.4 km (axis ratio 1.5:1) at the previously measured geometric albedo of 0.05 ± 0.02. We explored a range of continuous and impulsive emission models to simultaneously fit the measured surface brightness profile, width, and position angle of the antisolar tail. Preferred fits invoke protracted emission, over a period of 150 days or less, of dust grains following a differential power-law size distribution with index 3.25 ≤q ≤ 3.5 and with a wide range of sizes. Ultra-low surface brightness dust projected in the sunward direction is a remnant from emission activity occurring in previous orbits, and consists of the largest (≥cm-sized) particles. Ejection velocities of one-micron-sized particles are comparable to the ~1.8 m s<SUP>–1</SUP> gravitational escape speed of the nucleus, while larger particles are released at speeds less than the gravitational escape velocity. The observations are consistent with, but do not prove, a hybrid hypothesis in which mass loss is driven by gas drag from the sublimation of near-surface water ice, but escape is aided by centripetal acceleration from the rotation of the elongated nucleus. No plausible alternative hypothesis has been identified.</P>

Male Oxidative Stress Infertility (MOSI): Proposed Terminology and Clinical Practice Guidelines for Management of Idiopathic Male Infertility

Ashok Agarwal,Neel Parekh,Manesh Kumar Panner Selvam,Ralf Henkel,Rupin Shah,Sheryl T. Homa,Ranjith Ramasamy,Edmund Ko,Kelton Tremellen,Sandro Esteves,Ahmad Majzoub,Juan G. Alvarez,David K. Gardner,Cha 대한남성과학회 2019 The World Journal of Men's Health Vol.37 No.3

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm’s potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.

A population-based study of breast implant illness

Magno-Padron, David A.,Luo, Jessica,Jessop, Terry C.,Garlick, Jared W.,Manum, Joanna S.,Carter, Gentry C.,Agarwal, Jayant P.,Kwok, Alvin C. Korean Society of Plastic and Reconstructive Surge 2021 Archives of Plastic Surgery Vol.48 No.4

Background Despite evidence supporting the safety of breast implants, some women associate their implants with adverse health effects and have called this syndrome "breast implant illness." We sought to characterize breast implant illness symptoms and to report how implant removal affects their symptoms. Methods An anonymous 20 question survey was administered to the Facebook group: "UTAH Breast Implant Illness" to characterize the symptoms these women attributed to their breast implants. Several questions allowed us to evaluate how implant removal affected women's symptoms. Results Of the 182 respondents, 97% report that implants negatively affect their health and 95% identify these symptoms with breast implant illness. Ninety-six percent of respondents had implants placed for cosmetic reasons and 51% had silicone implants. The most common symptoms associated with breast implant illness are brain fog (95%), fatigue (92%), joint pain (80%), and hair loss (74%). Sixty percent of respondents learned about breast implant illness from family/friends and/or social media platforms (56%), 40% of respondents had their implants removed, and 97% report relief of their symptoms post-removal (23% complete, 74% partial). Following explantation, there was a significant improvement in all but one reported symptom. An association was found between the number of symptoms reported prior to explantation and the number of symptoms resolving following explantation. Conclusions Breast implant illness is a syndrome characterized by fatigue, decreased focus, hair loss, and joint pain after the placement of breast implants. Nearly all patients report improvement of symptoms after implant removal. Significant efforts should be made to better understand breast implant illness and its etiology.

Comparison of hepatic MDCT, MRI, and DSA to explant pathology for the detection and treatment planning of hepatocellular carcinoma

( Lauren M. Ladd ),( Temel Tirkes ),( Mark Tann ),( David M Agarwal ),( Matthew S Johnson ),( Bilal Tahir ),( Kumaresan Sandrasegaran ) 대한간학회 2016 Clinical and Molecular Hepatology(대한간학회지) Vol.22 No.4

Background/Aims: The diagnosis and treatment plan for hepatocellular carcinoma (HCC) can be made from radiologic imaging. However, lesion detection may vary depending on the imaging modality. This study aims to evaluate the sensitivities of hepatic multidetector computed tomography (MDCT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) in the detection of HCC and the consequent management impact on potential liver transplant patients. Methods: One hundred and sixteen HCC lesions were analyzed in 41 patients who received an orthotopic liver transplant (OLT). All of the patients underwent pretransplantation hepatic DSA, MDCT, and/or MRI. The imaging results were independently reviewed retrospectively in a blinded fashion by two interventional and two abdominal radiologists. The liver explant pathology was used as the gold standard for assessing each imaging modality. Results: The sensitivity for overall HCC detection was higher for cross-sectional imaging using MRI (51.5%, 95% confidence interval [CI]=36.2-58.4%) and MDCT (49.8%, 95% CI=43.7-55.9%) than for DSA (41.7%, 95% CI=36.2-47.3%) (P=0.05). The difference in false-positive rate was not statistically significant between MRI (22%), MDCT (29%), and DSA (29%) (P=0.67). The sensitivity was significantly higher for detecting right lobe lesions than left lobe lesions for all modalities (MRI: 56.1% vs. 43.1%, MDCT: 55.0% vs. 42.0%, and DSA: 46.9% vs. 33.9%; all P<0.01). The sensitivities of the three imaging modalities were also higher for lesions ≥2 cm vs. <2 cm (MRI: 73.4% vs. 32.7%, MDCT: 66.9% vs. 33.8%, and DSA: 62.2% vs. 24.1%; all P<0.01). The interobserver correlation was rated as very good to excellent. Conclusions: The sensitivity for detecting HCC is higher for MRI and MDCT than for DSA, and so cross-sectional imaging modalities should be used to evaluate OLT candidacy. (Clin Mol Hepatol 2016;22:450-457)

Estrogen receptor-α, progesterone receptor, and c-erbB/HER-family receptor mRNA detection and phenotype analysis in spontaneous canine models of breast cancer

Farruk M. Lutful Kabir,Patricia DeInnocentes,Payal Agarwal,Christopher P. Mill,David J. Riese 2nd,R. Curtis Bird 대한수의학회 2017 Journal of Veterinary Science Vol.18 No.2

Well characterized, stable, p16-defective canine mammary cancer (CMT) cell lines and normal canine mammary epithelial cells were used to investigate expression of the major breast cancer-specific hormone receptors estrogen receptor alpha (ER1) and progesterone receptor (PR) as well as luminal epithelial-specific proto-oncogenes encoding c-erbB-1 (epidermal growth factor receptor/EGFr), c-erbB-2/HER2, c-erbB-3, and c-erbB-4 receptors. The investigation developed and validated quantitative reverse transcriptase polymerase chain reaction assays for each transcript to provide rapid assessment of breast cancer phenotypes for canine cancers, based on ER1, PR, and c-erbB-2/HER2 expressions, similar to those in human disease. Roles for relatively underexplored c-erbB-3 and c-erbB-4 receptor expressions in each of these breast cancer phenotypes were also evaluated. Each quantitative assay was validated by assessment of amplicon size and DNA sequencing following amplification. Differential expression of ER1, PR, and c-erbB-2 in CMT cell lines clearly defined distinct human-like breast cancer phenotypes for a selection of CMT-derived cell lines. Expression profiles for EGFr family genes c-erbB-3 and c-erbB-4 in CMT models also provided an enriched classification of canine breast cancer identifying new extended phenotypes beyond the conventional luminal-basal characterization used in human breast cancer.

Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting

Nam, J.W.,Rissland, Olivia S.,Koppstein, D.,Abreu-Goodger, C.,Jan, Calvin H.,Agarwal, V.,Yildirim, Muhammed A.,Rodriguez, A.,Bartel, David P. Cell Press 2014 Molecular cell Vol.53 No.6

MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development-with its resulting diversity of cellular contexts-impacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3' UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3' UTR isoforms revealed that they influence ~10% of predicted targets when comparing any two cell types. Indeed, considering alternative 3' UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3' UTR landscape helps predict targeting efficacy and explain differential regulation that is observed.

MFF Regulation of Mitochondrial Cell Death Is a Therapeutic Target in Cancer

Seo, Jae Ho,Chae, Young Chan,Kossenkov, Andrew V.,Lee, Yu Geon,Tang, Hsin-Yao,Agarwal, Ekta,Gabrilovich, Dmitry I.,Languino, Lucia R.,Speicher, David W.,Shastrula, Prashanth K.,Storaci, Alessandra Mar American Association for Cancer Research 2019 Cancer Research Vol.79 No.24

<P>These findings describe mitochondrial fission regulation using a peptidomimetic agent that disturbs the MFF-VDAC complex and displays anticancer activity in multiple tumor models.</P><P><B></B></P><P>The regulators of mitochondrial cell death in cancer have remained elusive, hampering the development of new therapies. Here, we showed that protein isoforms of mitochondrial fission factor (MFF1 and MFF2), a molecule that controls mitochondrial size and shape, that is, mitochondrial dynamics, were overexpressed in patients with non–small cell lung cancer and formed homo- and heterodimeric complexes with the voltage-dependent anion channel-1 (VDAC1), a key regulator of mitochondrial outer membrane permeability. MFF inserted into the interior hole of the VDAC1 ring using Arg225, Arg236, and Gln241 as key contact sites. A cell-permeable MFF Ser223-Leu243 <SMALL>D</SMALL>-enantiomeric peptidomimetic disrupted the MFF–VDAC1 complex, acutely depolarized mitochondria, and triggered cell death in heterogeneous tumor types, including drug-resistant melanoma, but had no effect on normal cells. In preclinical models, treatment with the MFF peptidomimetic was well-tolerated and demonstrated anticancer activity in patient-derived xenografts, primary breast and lung adenocarcinoma 3D organoids, and glioblastoma neurospheres. These data identify the MFF–VDAC1 complex as a novel regulator of mitochondrial cell death and an actionable therapeutic target in cancer.</P><P><B>Significance:</B></P><P>These findings describe mitochondrial fission regulation using a peptidomimetic agent that disturbs the MFF–VDAC complex and displays anticancer activity in multiple tumor models.</P><P><I>See related commentary by Rao, p. 6074</I></P>