Spatial and temporal variations in earthquake stress drop on Gofar Transform Fault, East Pacific Rise : implications for fault strength

Author Posting. © American Geophysical Union, 2018. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 123 (2018): 7722-7740, doi:10.1029/2018JB015942.On Gofar Transform Fault on the East Pacific Rise, the largest earthquakes (6.0 ≤ MW ≤ 6.2) have repeatedly ruptured the same portion of the fault, while intervening fault segments host swarms of microearthquakes. These long‐term patterns in earthquake occurrence suggest that heterogeneous fault zone properties control earthquake behavior. Using waveforms from ocean bottom seismometers that recorded seismicity before and after an anticipated 2008 MW 6.0 mainshock, we investigate the role that differences in material properties have on earthquake rupture at Gofar. We determine stress drop for 138 earthquakes (2.3 ≤ MW ≤ 4.0) that occurred within and between the rupture areas of large earthquakes. Stress drops are calculated from corner frequencies derived using an empirical Green's function spectral ratio method, and seismic moments are obtained by fitting the omega‐square source model to the low frequency amplitude of the displacement spectrum. Our analysis yields stress drops from 0.04 to 3.2 MPa with statistically significant spatial variation, including ~2 times higher average stress drop in fault segments where large earthquakes also occur compared to fault segments that host earthquake swarms. We find an inverse correlation between stress drop and P wave velocity reduction, which we interpret as the effect of fault zone damage on the ability of the fault to store strain energy that leads to our spatial variations in stress drop. Additionally, we observe lower stress drops following the MW 6.0 mainshock, consistent with increased damage and decreased fault strength after a large earthquake.W. M. Keck Foundation; National Science Foundation Division of Ocean Sciences (OCE) Grant Number: 13525652019-03-0

Budesonide Oral Suspension Improves Symptomatic, Endoscopic, and Histologic Parameters Compared With Placebo in Patients With Eosinophilic Esophagitis

Background & Aims Pharmacologic treatment of eosinophilic esophagitis (EoE) is limited to off-label use of corticosteroids not optimized for esophageal delivery. We performed a randomized, controlled phase 2 trial to assess the ability of budesonide oral suspension (BOS), a novel muco-adherent topical steroid formulation, to reduce symptoms and esophageal eosinophilia in adolescents and adults with EoE. Methods In this multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 93 EoE patients between the ages of 11 and 40 years with dysphagia and active esophageal eosinophilia were randomized to receive either BOS 2 mg or placebo twice daily for 12 weeks. Co-primary outcomes were change in Dysphagia Symptom Questionnaire (DSQ) score from baseline, and proportion of patients with a histologic response (≤6 eosinophils/high-power field) after treatment. Endoscopic severity scores and safety parameters were assessed. Results At baseline, mean DSQ scores were 29.3 and 29.0, and mean peak eosinophil counts were 156 and 130 per hpf in the BOS and placebo groups, respectively. After treatment, DSQ scores were 15.0 and 21.5, and mean peak eosinophil counts were 39 and 113 per high-power field, respectively (P < .05 for all). For BOS vs placebo, change in DSQ score was −14.3 vs −7.5 (P = .0096), histologic response rates were 39% vs 3% (P < .0001), and change in endoscopic severity score was −3.8 vs 0.4 (P < .0001). Adverse events were similar between groups. Conclusions Treatment with BOS was well tolerated in adolescent and young adult patients with EoE and resulted in improvement in symptomatic, endoscopic, and histologic parameters using validated outcome instruments

Chloroquine Analogues as Leads against Pneumocystis Lung Pathogens

The impact of Pneumocystis pneumonia (PcP) on morbidity and mortality remains substantial for immunocompromised individuals, including those afflicted by HIV infection, organ transplantation, cancer, autoimmune diseases, or subject to chemotherapy or corticosteroid-based therapies. Previous work from our group has shown that repurposing antimalarial compounds for PcP holds promise for treatment of this opportunistic infection. Following our previous discovery of chloroquine analogues with dual-stage antimalarial action both in vitro and in vivo, we now report the potent action of these compounds on Pneumocystis carinii in vitro Identification of chloroquine analogues as anti-PcP leads is an unprecedented finding.info:eu-repo/semantics/publishedVersio

Anti-Pneumocystis carinii and antiplasmodial activities of primaquine-derived imidazolidin-4-ones

A series of primaquine-derived imidazolidin-4-ones were screened for their in vitro activity against Pneumocystis carinii and Plasmodium falciparum W2 strain. Most compounds were active against P. carinii above 10 mu g/mL and displayed slight to marked activity. The imidazolidin-4-ones most active against P. carinii were also those most active antiplasmodial agents, in the mu M range. One of the tested imidazolidin-4-ones was slightly more active than the parent primaquine and may represent a lead compound for the development of novel anti-P. carinii 8-aminoquinolines with increased stability and resistance to metabolic inactivation

PRIMACENES: novel non-cytotoxic primaquine-ferrocene conjugates with anti-Pneumocystis carinii activity

Primacenes, novel ferrocene-primaquine conjugates, were synthesized and screened for their antimalarial and anti-pneumocystis activity. Primacenes obtained by coupling primaquine amino acid derivatives to ferrocenoic acid were significantly active against Pneumocystis carinii and devoid of cytotoxicity, thus being more selective than the parent drug

Anti-pneumoscystis carinni activitiy of primaquine imidazolidin-4-ones

Pneumocystis pneumonia (PCP) is one of the most frequent causes of mortality among HIV-infected patients. Primaquine (PQ) is an antimalarial 8-aminoquinoline effective against PCP when given in combination with clindamycin. This has drawn the attention of Medicinal Chemists towards the anti-PCP activity of 8-aminoquinolines, not only confined to those exhibiting antimalarial activity [1]. It is thought that anti-PCP 8-aminoquinolines exert their anti-PCP activity by acting on the electronic transport and redox system of the P. carinii pathogen [1]. Recently, our research group has been developing imidazolidin-4-one derivatives of PQ (Scheme 1), targeting novel compounds with improved therapeutic action, namely, higher resistance to metabolic inactivation, lower toxicity and equal or higher antimalarial activity than that of the parent drug [2,3]. These imidazolidin-4-ones were seen to block the transmission of rodent malaria, caused by Plasmodium berghei on BalbC mice, to the mosquito vector Anopheles stephensi [3]. The anti-PCP activity of our PQ derivatives is now under study and preliminary in vitro assays [4] show that some of the compounds exhibit slight to moderate activity after a 72 h incubation period against P. carinii. In one case, the IC50 was comparable to that of parent PQ. Both these studies and forthcoming results from ongoing biological assays will be presented and discussed

Identification of ovarian cancer metastatic miRNAs

Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease.<br/

Localization of a human T-cell-specific gene, RANTES (D17S136E), to chromosome 17q11.2-q12

We report here the localization of the gene for a human T-cell-specific molecule, designated RANTES, to human chromosome region 17q11.2-q12 by in situ hybridization and analysis of somatic cell hybrids using a cDNA probe to the gene. We have recently shown that this gene, which encodes a small, secreted, putative lymphokine, is a member of a larger gene family some of whose members reside on chromosome 4 but most of whose members have not to date been mapped. A secondary hybridization peak was noted on the region of human chromosome 5q31-q34, which may represent the location of other members of the gene family. Interestingly, this latter region overlaps with the location of an extended linked cluster of growth factor and receptor genes, some of which may be coregulated with members of the RANTES gene family.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28717/1/0000538.pd

Instrument development, data collection, and characteristics of practices, staff, and measures in the Improving Quality of Care in Diabetes (iQuaD) Study

Peer reviewedPublisher PD