Search

The purpose of this manuscript is to establish an antiracism framework for dental education. Since the accreditation process is an influential driver of institutional culture and policy in dental education, the focus of the framework is the Commission on Dental Accreditation (CODA) standards for predoctoral education.The authors of this manuscript reviewed each CODA predoctoral standard for opportunities to incorporate antiracism strategies. Eight standards were identified under themes of diversity (Standards 1-3, 1-4, 4-4), curriculum development (Standards 2-17, 2-26), and faculty recruitment and promotion (Standards 3-1, 3-4, 3-5). Guided primarily by National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care, a logic model approach was used to critically assess those standards for opportunities to establish antiracism strategies, with anticipated outcomes and impacts.Strategies highlighted a need to improve recruitment, admissions, and accountability among dental schools to address the low numbers of historically underrepresented racial and ethnic (HURE) students and faculty. They emphasized the inclusion of racism in curricula geared toward training dental students to provide care to HURE populations. Finally, there are opportunities to improve accountability that dental schools are providing equitable opportunities for career advancement among HURE faculty, with consideration of conflicting demands for scholarship with HURE student mentoring, role modeling, teaching, and/or service.The framework identifies gaps in CODA standards where racism may be allowed to fester, provides specific antiracism strategies to strengthen antiracism through the accreditation process, and offers dental education programs, a process for evaluating and establishing their own antiracism strategies.

Treating acute kidney injury (AKI) represents an important unmet medical need both in terms of the seriousness of this medical problem and the number of patients. There is also a large untapped market opportunity in treating AKI. Over the years, there has been much effort in search of therapeutics with minimal success. However, over the same time period, new understanding of the underlying pathobiology and molecular mechanisms of kidney injury have undoubtedly helped the search for new therapeutics. Along this line, carbon monoxide (CO) has emerged as a promising therapeutic agent because of its demonstrated cytoprotective, and immunomodulatory effects. CO has also been shown to sensitize cancer, but not normal cells, to chemotherapy. This is particularly important in treating cisplatin-induced AKI, a common clinical problem that develops in patients receiving cisplatin therapies for a number of different solid organ malignancies. This review will examine and make the case that CO be developed into a therapeutic agent against AKI.

The Chief Justice of the Delaware Supreme Court begins by invoking the New Deal, and expressing admiration for the way its goals and some of its social programs have been put into practice by Northern European social democracies. Most important are their protections for workers and the unemployed—protections the Judge finds deplorably absent in U.S. law and corporate labor practices. Nevertheless, when contemplating how corporate boards in the U.S. might respond to the growing demand for U.S. public companies to address social problems like the environment and economic inequality, the Delaware judge falls back on the prescription of Adolph Berle, who, though one of the framers of the New Deal, insisted that companies “stick to their knitting” by putting shareholders first as the only way of ensuring the accountability of corporate managements and boards. Harvard Law's Mark Roe responds with a defense of corporate America against the charge of corporate short‐termism by noting that, although U.S. capital expenditures have declined in the past 15–20 years, corporate investment in R&D and other intangible assets have both grown sharply. Corporate distributions in the form of dividends and stock buybacks are rising, but so have the net borrowings of the companies making the distributions, leaving the cash balances of U.S. companies also near record levels. And the remarkably high valuations of successful high tech companies are themselves forceful rebuttals of the idea that pressure from the stock market for current earnings is a serious deterrent to investment and innovation. The University of Pennsylvania's Jill Fisch follows Roe's dismissal of the short‐termism argument with even more forceful questioning of whether corporate America in fact has a major governance problem. U.S. companies have been taking voluntary measures to address environmental problems—in some cases even in the face of federal deregulatory initiatives—and many have raised their workers’ wages, without any challenges (and often with encouragement) from their shareholders. And echoing Justice Strine's concerns, Fisch also ends up questioning the premise that companies can be asked to define a single social purpose (other than maximizing shareholder value) that would be appropriate for, and end up satisfying, all their different stakeholders. Columbia Business School's Bruce Kogut closes with the suggestion that our greatest problems today may be coming not from the shortsightedness and other failings of corporations and corporate law, but from “deep distrust of the competence of the state.” Kogut's main prescription is that to take advantage of the enormous potential gains from effective arm's‐length collaboration between business and the public sector, governments at all levels should find ways to strike “Coasian bargains” with the private sector that makes the best possible uses of the core competencies and resources of each.

Induction of mammalian heme oxygenase (HO)-1 and exposure of animals to carbon monoxide (CO) ameliorates experimental colitis. When enteric bacteria, including Escherichia coli, are exposed to low iron conditions, they express an HO-like enzyme, chuS, and metabolize heme into iron, biliverdin and CO. Given the abundance of enteric bacteria residing in the intestinal lumen, our postulate was that commensal intestinal bacteria may be a significant source of CO and those that express chuS and other Ho-like molecules suppress inflammatory immune responses through release of CO. According to real-time PCR, exposure of mice to CO results in changes in enteric bacterial composition and increases E. coli 16S and chuS DNA. Moreover, the severity of experimental colitis correlates positively with E. coli chuS expression in IL-10 deficient mice. To explore functional roles, E. coli were genetically modified to overexpress chuS or the chuS gene was deleted. Co-culture of chuS-overexpressing E. coli with bone marrow-derived macrophages resulted in less IL-12p40 and greater IL-10 secretion than in wild-type or chuS-deficient E. coli. Mice infected with chuS-overexpressing E. coli have more hepatic CO and less serum IL-12 p40 than mice infected with chuS-deficient E. coli. Thus, CO alters the composition of the commensal intestinal microbiota and expands populations of E. coli that harbor the chuS gene. These bacteria are capable of attenuating innate immune responses through expression of chuS. Bacterial HO-like molecules and bacteria-derived CO may represent novel targets for therapeutic intervention in inflammatory conditions.

Imitating nature's approach in nucleophile-activated formaldehyde dehydrogenation, air-stable ruthenium complexes proved to be exquisite catalysts for the dehydrogenation of formaldehyde hydrate as well as for the transfer hydrogenation to unsaturated organic substrates at loadings as low as 0.5 mol %. Concatenation of the chemical hydrogen-fixation route with an oxidase-mediated activation of methanol gives an artificial methylotrophic in vitro metabolism providing methanol-derived reduction equivalents for synthetic hydrogenation purposes. Moreover, for the first time methanol reforming at room temperature was achieved on the basis of this bioinduced dehydrogenation path delivering hydrogen gas from aqueous methanol.

BACKGROUND: Excluding disinfectants, pyrethrins and pyrethroids are the pesticides used most commonly in and around homes. Respiratory effects and paresthesia are among the concerns about pyrethrin/pyrethroid exposures. METHODS: Acute pesticide-related illness/injury cases were identified from the Sentinel Event Notification System for Occupational Risks-Pesticides Program and the California Department of Pesticide Regulation from 2000-2008. Characteristics and incidence rates were determined for acute pyrethrin/pyrethroid-related illness/injury cases. Logistic regression analyses were performed to determine odds of respiratory and dermal symptoms in persons with illness/injury following pyrethrin/pyrethroid exposure compared to persons with illness/injury following exposure to other pesticides. RESULTS: A total of 4,974 cases of acute pyrethrin/pyrethroid-related illness were identified. Incidence rates increased over time, reaching 8 cases/million population in 2008. The majority of cases were low severity (85%) and 34% were work-related. Respiratory effects were the most common symptoms reported (48%). Risk of acute respiratory effects were significantly elevated among persons exposed only to pyrethrins (adjusted odds ratio [aOR] 1.79; 95% confidence interval [95% CI]: 1.49-2.16), only to pyrethroids (aOR 1.99 95% CI: 1.77-2.24), to a mixture of pyrethroids (aOR 2.36; 95% CI: 1.99-2.81) or to a mixture containing both pyrethrins and pyrethroids (aOR 2.99; 95% CI: 2.33-3.84) compared to those with illness arising from exposure to other pesticides. The most common factors contributing to pyrethrin/pyrethroid-related illness included exposure from spills/splashes, improper storage, and failure to evacuate during pesticide application. CONCLUSIONS: The magnitude of acute pyrethrin/pyrethroid-related illness/injury is relatively low but is increasing. As such, additional measures to prevent them are needed. Am. J. Ind. Med. 9999:1-16, 2013. © 2013 Wiley Periodicals, Inc. Language: en

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in the tryptophan catabolism, has recently emerged as an important immunosuppressive enzyme involved in the regulation of both physiologic (maternal tolerance), as well as pathologic (neoplasia, autoimmune diseases, asthma) processes. Accumulating evidence points to a role for IDO in suppressing T-cell responses, thereby promoting tolerance. In the present study, we investigate the effects of adenovirus-mediated gene therapy with IDO on the acute rejection of the transplanted kidneys. METHODS: The experiments were performed in a rat Fisher to Lewis acute renal rejection model. RGD modified adenovirus carrying IDO gene (RGD-AdTIDO, n = 9) or RGD modified adenovirus carrying green fluorescent protein gene (RGD-AdTL, n = 8) were injected into the renal artery of the donor kidney before transplantation. A group receiving saline (n = 8) served as control. Rats were sacrificed after 7 days. RESULTS: Successful gene delivery was confirmed with real-time polymerase chain reaction and immunohistochemistry. RGD-AdTIDO significantly decreased elevated plasma creatinine (93.7 ± 18.9 µmol/l) compared to the RGD-AdTL (248.2 ± 43.6 µmol/l) and saline (228.3 ± 46.4 µmol/l) treated rats. Moreover, RGD-AdTIDO therapy diminished the infiltration of CD8+ T cells and macrophages into the graft and reduced renal interstitial pre-fibrosis. Also, it limited the up-regulation of kidney injury molecule-1, interleukin (IL)-2, IL-17 and transforming growth factor-β mRNA expression, and increased foxp3 mRNA expression compared to controls. CONCLUSIONS: RGD-AdTIDO therapy improves renal function and morphology in a clinically relevant model of acute rejection.

Here, we quantify relationships between wind farm efficiency and wind speed, direction, turbulence and atmospheric stability using power output from the large offshore wind farm at Nysted in Denmark. Wake losses are, as expected, most strongly related to wind speed variations through the turbine thrust coefficient; with direction, atmospheric stability and turbulence as important second order effects. While the wind farm efficiency is highly dependent on the distribution of wind speeds and wind direction, it is shown that the impact of turbine spacing on wake losses and turbine efficiency can be quantified, albeit with relatively large uncertainty due to stochastic effects in the data. There is evidence of the ‘deep array effect’ in that wake losses in the centre of the wind farm are under-estimated by the wind farm model WAsP, although overall efficiency of the wind farm is well predicted due to compensating edge effects. Copyright © 2010 John Wiley & Sons, Ltd.

Item does not contain fulltext Caveolae are a subtype of cholesterol-enriched lipid microdomains/rafts that are routinely detected as vesicles pinching off from the plasma membrane. Caveolin-1 is an essential component of caveolae. Hepatic caveolin-1 plays an important role in liver regeneration and lipid metabolism. Expression of caveolin-1 in hepatocytes is relatively low, and it has been suggested to also reside at other subcellular locations than the plasma membrane. Recently, we found that the peroxisomal membrane contains lipid microdomains. Like caveolin-1, hepatic peroxisomes are involved in lipid metabolism. Here, we analyzed the subcellular location of caveolin-1 in rat hepatocytes. The subcellular location of rat hepatocyte caveolin-1 was analyzed by cell fractionation procedures, immunofluorescence, and immuno-electron microscopy. Green fluorescent protein (GFP)-tagged caveolin-1 was expressed in rat hepatocytes. Lipid rafts were characterized after Triton X-100 or Lubrol WX extraction of purified peroxisomes. Fenofibric acid-dependent regulation of caveolin-1 was analyzed. Peroxisome biogenesis was studied in rat hepatocytes after RNA interference-mediated silencing of caveolin-1 and caveolin-1 knockout mice. Cell fractionation and microscopic analyses reveal that caveolin-1 colocalizes with peroxisomal marker proteins (catalase, the 70 kDa peroxisomal membrane protein PMP70, the adrenoleukodystrophy protein ALDP, Pex14p, and the bile acid-coenzyme A:amino acid N-acyltransferase BAAT) in rat hepatocytes. Artificially expressed GFP-caveolin-1 accumulated in catalase-positive organelles. Peroxisomal caveolin-1 is associated with detergent-resistant microdomains. Caveolin-1 expression is strongly repressed by the peroxisome proliferator-activated receptor-alpha agonist fenofibric acid. Targeting of peroxisomal matrix proteins and peroxisome number and shape were not altered in rat hepatocytes with 70%-80% reduced caveolin-1 levels and in livers of caveolin-1 knockout mice. CONCLUSION: Caveolin-1 is enriched in peroxisomes of hepatocytes. Caveolin-1 is not required for peroxisome biogenesis, but this unique subcellular location may determine its important role in hepatocyte proliferation and lipid metabolism. 01 mei 2010

The paper presents research to develop a model complex that takes into account the interaction between the wind farm and the atmosphere, and between closely spaced wind farms. Six models have been reviewed and developed/adapted for use in wind farm modelling, covering scales from several hundred kilometres down to the size of the individual wind turbine. Flow within wind farms is difficult to predict. The analytical and modified WAsP/park models show promise; however, these require further development/evaluation. For the flow downwind of the wind farm, several intermediate-scale models fit the available data rather well, and may be candidates for the other half of the two-model complex which we aim at building. Copyright © 2009 John Wiley & Sons, Ltd.

This paper deals with modelling of power fluctuations from large wind farms. The modelling is supported and validated using wind speed and power measurements from the two large offshore wind farms in Denmark. The time scale in focus is from 1 min to a couple of hours, where significant power fluctuations have been observed from these wind farms. Power and wind speed are measured with 1 s sampling time in all individual wind turbines in almost 1 year, which provides a substantial database for the analyses. The paper deals with diversified models representing each wind turbine individually and with aggregation of a wind farm to be represented by a single large wind turbine model. Copyright © 2007 John Wiley & Sons, Ltd.

Carbon monoxide (CO), which is produced endogenously in the breakdown of heme, has been recognized as an important physiological second messenger similar to NO. Additionally, pharmacological delivery of CO is protective in numerous models of injury, including ischemia/reperfusion, transplantation, hemorrhagic shock, and endotoxemia. However, the mechanism of action of CO is only partially elucidated focused primarily on how it modulates the cellular response to stress. The purpose of these investigations is to test the hypothesis that CO acts via inhibition of cytochrome c oxidase leading to the generation of low levels of reactive oxygen species (ROS) that in turn mediate subsequent adaptive signaling. We show here that CO increases ROS generation in RAW 264.7 cells, which is inhibited by antimycin A and is absent in respiration-deficient rho0 cells. CO inhibits cytochrome c oxidase, while maintaining cellular ATP levels and increasing mitochondrial membrane potential. The addition of antioxidants or inhibition of complex III of the electron transport chain by antimycin A attenuates the inhibitory effects of CO on lipopolysaccharide (LPS)-induced TNF-alpha and blocked CO-induced p38 MAPK phosphorylation, which we previously have shown to be important in the anti-inflammatory effects of CO.

The glycoproteome is a major subproteome present in human plasma. In this study, we isolated and characterized approximately 150 glycoproteins from the human plasma and serum samples provided by HUPO using a multilectin affinity column. The corresponding tryptic digest was separated by RP-HPLC coupled to an IT mass spectrometer (3-D LCQ). Also in this study, a new system, namely an Ettan MDLC system coupled to a linear ITLTQ, was compared with the previous LCQ platform and gave a greater number of protein identifications, as well as better quality. When we compared the composition of the glycoproteomes for the plasma and serum samples there was a close correlation between the samples, except for the absence of fibrinogen from the identified-protein list in the latter sample, which was presumably as a result of the clotting process. In addition, the analysis of the samples from three ethnic specimens, Caucasian American, Asian American, and African American, were very similar but showed a higher angiotensinogen plasma level and a lower histidine-rich glycoprotein level in Caucasian American samples, and a lower vitronectin level in African American blood samples.

Carbon monoxide (CO), a product of organic oxidation processes, arises in vivo during cellular metabolism, most notably heme degradation. CO binds to the heme iron of most hemoproteins. Tissue hypoxia following hemoglobin saturation represents a principle cause of CO-induced mortality in higher organisms, though cellular targets cannot be excluded. Despite extreme toxicity at high concentrations, low concentrations of CO can confer cytoprotection during ischemia/reperfusion or inflammation-induced tissue injury. Likewise, heme oxygenase, an enzyme that produces CO, biliverdin and iron, as well as a secondary increase in ferritin synthesis, from the oxidation of heme, can confer protection in vivo and in vitro. CO has been shown to affect several intracellular signaling pathways, including guanylate cyclase, which generates guanosine 3':5' cyclic monophosphate and the mitogen-activated protein kinases (MAPK). Such pathways mediate, in part, the known vasoregulatory, anti-inflammatory, anti-apoptotic and anti-proliferative effects of this gas. Exogenous CO delivered at low concentrations is showing therapeutic potential as an anti-inflammatory agent and as such can modulate numerous pathophysiological states. This review will delve into the biological significance and medical applications of this gas molecule.

Objective : Inflammation is clearly implicated in the pathogenesis of cardiovascular disease, sepsis and respiratory disorders. The present study aimed to reveal the effect of biliverdin (BV) on the expression of pro/anti-inflammatory cytokines in whole human blood. Methods : Eight healthy males were recruited and 50 mLs of blood was collected into EDTA vacutainers. Whole blood was supplemented with BV (10 or 50 μM) in the presence or absence of 3 μg/mL lipopolysaccride for 4, 8 and 24 hours. Total RNA was purified at 4 h and plasma was collected at 4, 8 and 24 hours. Gene and protein expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-1Ra and IL-10) were analyzed using qRT-PCR and multiplex Luminex analysis. Results : Biliverdin inhibited LPS-mediated expression of IL-1 β and IL-1Ra in a dose dependent manner, showing a 50% decrease at 4 h (50 μM, P Conclusion : Biliverdin reduces LPS-induced expression of IL-1 β and IL-1Ra in whole human blood. This study is the first translational evidence to support BV’s use as anti-inflammatory agent in humans against LPS/sepsis.

Transplants of a spontaneous murine fibrosarcoma (FSaII) treated with intraperitoneal (i.p.) adenosine 5′-triphosphate (ATP) were studied in vitro, and in vivo in both C3H and nu/nu mice. In vivo daily ATP treatments caused a small dose-dependent reduction in the total neovascular lumen area and thallium washout. There was an associated reduction in tumor volume doubling time but a similar growth rate reduction was also seen in vitro where flow has no impact. Daily ATP treatments at the maximally tolerated dose (2 mmol/kg i.p.) did not significantly affect the pH nuclear magnetic resonance or the phosphocreatine/inorganic phosphate (PCr/Pi), βATP/Pi, or phosphomonoester (PME)/ βATP ratios. The acute systemic physiological effects of i.p. ATP were mild, consisting of a transient reduction in skin laser Doppler flow and mean arterial pressure. Systemic toxicities of ATP given as daily boluses at doses capable of producing significant growth retardation of FSaII tumors were transient. Our results are most consistent with the hypothesis that the growth retarding effects of ATP are primarily a result of a decreased proliferation rather than tumor cytotoxicity or systemic pathophysiology. The main toxicity of ATP at active dose levels is cardiovascular. ATP might be useful as a biological modifier of chemotherapy or radiation. © 1994 Wiley-Liss, Inc1 .