Quantitative biomonitoring in the Detroit River using Elliptio complanata: Verification of steady state correction factors and temporal trends of PCBs in water between 1998-2015

Quantitative biomonitoring methods were applied to determine PCB concentrations in water from the Detroit River over a 17 year period. During 2014, mussels were deployed for and extended duration (21-364 d) and time dependent PCB concentrations were fit to a bioaccumulation model to estimate elimination coefficients (ktot) and provide site specific calibration of mussel toxicokinetics. The site specific calibration and different ktot versus KOW relationships from the literature were used to correct for steady state. ∑PCB concentrations in water were not significantly dependent on the ktot values used indicating that individual variation exceeds error contributed by steady state correction factors. The model was then applied to estimate ∑PCB concentrations in water using the long term (1998-2015) data. ∑PCBs concentrations in water exhibited a significant decreasing trend with a half life of 9.12 years resulting in a drop in yearly geometric mean residues from 198.1 pg/L to 43.6 pg/L

HUMAN ADIPOSE-DERIVED STEM CELLS ATTENUATE CIGARETTE SMOKE INDUCED BONE MARROW HYPOPLASIA VIA SECRETION OF ANTI-INFLAMMATORY CYTOKINE TSG-6

poster abstractIntroduction We have previously observed bone marrow (BM) hypo-plasia in a murine model of chronic smoking, which was ameliorated by mu-rine adipose-derived stromal cells (ASC). This study was designed to test the hypothesis that ASC exert their marrow protective effects through key paracrine factors. Methods Mice (NSG or C57BL/6) were exposed to ciga-rette smoke (CS) for 1 day to 6 months. Human ASC or ASC conditioned media were administered through intravenous (i.v.) or intraperitoneal (i.p.) injections. Secretion of TSG-6 from ASC in response to TNF alpha and IL-1 beta were measured by ELISA. Expression of TSG-6 in ASC was knocked down by siRNA. BM hematopoietic progenitors were quantified by colony forming-unit assays. Possible engrafted human ASC in mouse BM were ex-amined by anti-human nuclei staining. Results The myelossupressive effect of cigarette smoking occurred acutely (1 day: 65.6% of nonsmoking control, NSC, p0.05) or ASC conditioned media (105.7% NSC, p>0.05). Inflammatory cytokines (TNF alpha and IL-1 beta) elevated in smokers (Kuschner et al, 1996; de Maat et al, 2002) demonstrated strong cross-species stimulatory effects on secretions of an anti-inflammatory cytokine, TSG-6 from ASC (TNF alpha: 8.7 +/- 1.3 fold, IL-1 beta: 8.2 +/- 1.1 fold). Knocking down TSG-6 (>90%) abolished the marrow-protective effect of ASC. No human cells were detected in recipient mouse bone marrow. Conclusions The pro-tective effects of ASC against smoking-induced myelosuppression are medi-ated by trophic factors rather than cell engraftment or differentiation. TSG-6 appears to play a significant role in the modulatory pathway: smoke--inflammatory cytokine release--TSG6 secretion from ASC--bone marrow protection

Ethanol Administration Produces Divergent Changes in GABAergic Neuroactive Steroid Immunohistochemistry in the Rat Brain

The 5α-reduced pregnane neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP or allopregnanolone) is a potent positive modulator of GABAA receptors capable of modulating neuronal activity. In rats, systemic ethanol administration increases cerebral cortical and hippocampal levels of 3α,5α-THP, but the effects of ethanol on 3α,5α-THP levels in other brain regions are unknown. There is a large body of evidence suggesting that 3α,5α-THP enhances ethanol sensitivity, contributes to some behavioral effects of ethanol, and modulates ethanol reinforcement and motivation to drink. In the present study, we used immunohistochemistry (IHC) to determine ethanol-induced changes in cellular 3α,5α-THP expression in brain regions associated with ethanol actions and responses

Mucosal Perfusion Preservation by a Novel Shapeable Tissue Expander for Oral Reconstruction

Background: There are few methods for expanding oral mucosa, and these often cause complications such as tissue necrosis and expander eruption. This study examines mucosal blood perfusion following insertion of a novel shapeable hydrogel tissue expander (HTE). The canine model used subgingival insertion of HTE following tooth extraction and alveolar bone reduction. The primary goal of this study was to gain understanding of epithelial perfusion and reparative responses of gingival mucosa during HTE expansion. Methods: Nine Beagle dogs underwent bilateral premolar maxillary and mandibular tooth extraction. Three to four months later, HTE-contoured inserts were implanted submucosally under the buccal surface of the alveolar ridge. After removal and following a 6- to 7-month period of healing, new HTE implants were inserted at the same sites. The area was assessed weekly for tissue perfusion and volume of expansion. Biopsies for histological analysis were performed at the time of expander removal. Results: Within 2 weeks following the second insertion, blood flow returned to baseline (defined as the values of perfusion measurements at the presurgery assessment) and remained normal until hydrogel full expansion and removal. Volume expansion analysis revealed that the hydrogel doubled in volume. Histological assessment showed no macrophage or inflammatory infiltration of the mucosa. No superficial fibrosis, decreased vascularity, or mucosal change was seen. Conclusion: Maintenance of adequate tissue perfusion is a clinically important aspect of tissue expander performance to reduce risk of device loss or injury to the patient, particularly for areas with a history of previous surgeries

Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion Through Paracrine Factors

Abdominal aortic aneurysm (AAA) is a potentially lethal disease associated with immune activation-induced aortic degradation. We hypothesized that xenotransplantation of human adipose-derived stem cells (hADSCs) would reduce aortic inflammation and attenuate expansion in a murine AAA model. Modulatory effects of ADSCs on immune cell subtypes associated with AAA progression were investigated using human peripheral blood mononuclear cells (hPBMNCs) cocultured with ADSCs. Murine AAA was induced through elastase application to the abdominal aorta in C57BL/6 mice. ADSCs were administered intravenously, and aortic changes were determined by ultrasonography and videomicrometry. Circulating monocytes, aortic neutrophils, CD28− T cells, FoxP3+ regulatory T cells (Tregs), and CD206+ M2 macrophages were assessed at multiple terminal time points. In vitro, ADSCs induced M2 macrophage and Treg phenotypes while inhibiting neutrophil transmigration and lymphocyte activation without cellular contact. Intravenous ADSC delivery reduced aneurysmal expansion starting from day 4 [from baseline: 54.8% (saline) vs. 16.9% (ADSCs), n = 10 at baseline, n = 4 at day 4, p < 0.001], and the therapeutic effect persists through day 14 (from baseline: 64.1% saline vs. 24.6% ADSCs, n = 4, p < 0.01). ADSC administration increased aortic Tregs by 20-fold (n = 5, p < 0.01), while decreasing CD4+CD28− (-28%), CD8+CD28− T cells (-61%), and Ly6G/C+ neutrophils (-43%, n = 5, p < 0.05). Circulating CD115+CXCR1−LY6C+-activated monocytes decreased in the ADSC-treated group by day 7 (-60%, n = 10, p < 0.05), paralleled by an increase in aortic CD206+ M2 macrophages by 2.4-fold (n = 5, p < 0.05). Intravenously injected ADSCs transiently engrafted in the lung on day 1 without aortic engraftment at any time point. In conclusion, ADSCs exhibit pleiotropic immunomodulatory effects in vitro as well as in vivo during the development of AAA. The temporal evolution of these effects systemically as well as in aortic tissue suggests that ADSCs induce a sequence of anti-inflammatory cellular events mediated by paracrine factors, which leads to amelioration of AAA progression

Perfect state distinguishability and computational speedups with postselected closed timelike curves

Bennett and Schumacher's postselected quantum teleportation is a model of closed timelike curves (CTCs) that leads to results physically different from Deutsch's model. We show that even a single qubit passing through a postselected CTC (P-CTC) is sufficient to do any postselected quantum measurement, and we discuss an important difference between "Deutschian" CTCs (D-CTCs) and P-CTCs in which the future existence of a P-CTC might affect the present outcome of an experiment. Then, based on a suggestion of Bennett and Smith, we explicitly show how a party assisted by P-CTCs can distinguish a set of linearly independent quantum states, and we prove that it is not possible for such a party to distinguish a set of linearly dependent states. The power of P-CTCs is thus weaker than that of D-CTCs because the Holevo bound still applies to circuits using them regardless of their ability to conspire in violating the uncertainty principle. We then discuss how different notions of a quantum mixture that are indistinguishable in linear quantum mechanics lead to dramatically differing conclusions in a nonlinear quantum mechanics involving P-CTCs. Finally, we give explicit circuit constructions that can efficiently factor integers, efficiently solve any decision problem in the intersection of NP and coNP, and probabilistically solve any decision problem in NP. These circuits accomplish these tasks with just one qubit traveling back in time, and they exploit the ability of postselected closed timelike curves to create grandfather paradoxes for invalid answers.Comment: 15 pages, 4 figures; Foundations of Physics (2011

Complementary Embryonic and Adult Cell Populations Enhance Myocardial Repair in Rat Myocardial Injury Model

We compared the functional outcome of Isl-1+ cardiac progenitors, CD90+ bone marrow-derived progenitor cells, and the combination of the two in a rat myocardial infarction (MI) model. Isl-1+ cells were isolated from embryonic day 12.5 (E12.5) rat hearts and expanded in vitro. Thy-1+/CD90+ cells were isolated from the bone marrow of adult Sprague-Dawley rats by immunomagnetic cell sorting. Six-week-old female Sprague-Dawley rats underwent permanent left anterior descending (LAD) coronary artery ligation and received intramyocardial injection of either saline, Isl-1+ cells, CD90+ cells, or a combination of Isl-1+ and CD90+ cells, at the time of infarction. Cells were delivered transepicardially to the peri-infarct zone. Left ventricular function was assessed by transthoracic echocardiography at 1- and 4-week post-MI and by Millar catheterization (-dP/dt and +dP/dt) at 4-week post-MI. Fluorescence in situ hybridization (Isl-1+cells) and monochrystalline iron oxide nanoparticles labeling (MION; CD90+ cells) were performed to assess biodistribution of transplanted cells. Only the combination of cells demonstrated a significant improvement of cardiac function as assessed by anterior wall contractility, dP/dt (max), and dP/dt (min), compared to Isl-1+ or CD90+ cell monotherapies. In the combination cell group, viable cells were detected at week 4 when anterior wall motion was completely restored. In conclusion, the combination of Isl-1+ cardiac progenitors and adult bone marrow-derived CD90+ cells shows prolonged and robust myocardial tissue repair and provides support for the use of complementary cell populations to enhance myocardial repair

Enhancing Perception of Complex Sculptural Forms using Interactive Real-time Ray tracing

This paper looks at experiments into using real-time ray tracing to significantly enhance shape perception of complex three-dimensional digitally created structures. The author is a computational artist whose artistic practice explores the creation of intricate organic three-dimensional forms using simulation of morphogenesis. The generated forms are often extremely detailed, comprising tens of millions of cellular primitives. This often makes depth perception of the resulting structures difficult. His practice has explored various techniques to create presentable artefacts from the data, including high resolution prints, animated videos, stereoscopic installations, 3D printing and virtual reality. The author uses ray tracing techniques to turn the 3D data created from his morphogenetic simulations into visible artefacts. This is typically a time-consuming process, taking from seconds to minutes to create a single frame. The latest generation of graphics processing units offer dedicated hardware to accelerate ray tracing calculations. This potentially allows the generation of ray traced images, including self-shadowed complex structures and multiple levels of transparency, from new viewpoints at frame rates capable of real-time interaction. The author presents the results of his experiments using this technology with the aim of providing significantly enhanced perception of his generated three-dimensional structures by allowing user-initiated interaction to generate novel views, and utilizing depth cues such as stereopsis, depth from motion and defocus blurring. The intention is for these techniques to be usable to present new exhibitable works in a gallery context

Randomized Trial on the Effect of an Oral Spleen Tyrosine Kinase Inhibitor in the Treatment of IgA Nephropathy

Introduction: We reported increased spleen tyrosine kinase (SYK) expression in kidney biopsies of patients with IgA nephropathy (IgAN) and that inhibition of SYK reduces inflammatory cytokines production from IgA stimulated mesangial cells. / Methods: This study was a double-blind, randomized, placebo-controlled phase 2 trial of fostamatinib (an oral SYK inhibitor) in 76 patients with IgAN. Patients were randomized to receive placebo, fostamatinib at 100 mg or 150 mg twice daily for 24 weeks on top of maximum tolerated dose of renin-angiotensin system inhibitors. The primary end point was reduction of proteinuria. Secondary end points included change from baseline in estimated glomerular filtration rate (eGFR) and kidney histology. / Results: Although we could not detect significant reduction in proteinuria with fostamatinib overall, in a predetermined subgroup analysis, there was a trend for dose-dependent reduction in median proteinuria (from baseline to 24 weeks by 14%, 27%, and 36% in the placebo, fostamatinib 100 mg, and 150 mg groups, respectively) in patients with baseline urinary protein-to-creatinine ratios (UPCR) more than 1000 mg/g. Kidney function (eGFR) remained stable in all groups. Fostamatinib was well-tolerated. Side effects included diarrhea, hypertension, and increased liver enzymes. Thirty-nine patients underwent repeat biopsy showing reductions in SYK staining associated with therapy at low dose (−1.5 vs. 1.7 SYK+ cells/glomerulus in the placebo group, P < 0.05). / Conclusions: There was a trend toward reduction in proteinuria with fostamatinib in a predefined analysis of high risk patients with IgAN despite maximal care, as defined by baseline UPCR greater than 1000 mg/g. Further study may be warranted