The role of glutaredoxin-1 on B16F0 melanoma growth and angiogenesis in diet-induced diabetic mice

OBJECTIVES: Recent studies have elucidated that diabetes mellitus (DM) patients exhibit an accelerated tumor progression, but the mechanism of its regulation is not yet fully understood. The following study seeks to examine the role of angiogenic factors in the growth of subcutaneously injected melanoma cancer using a diet-induced type II diabetic mouse model. METHODS: C57BL/6 mice were fed either a regular or high-fat, high-sucrose (HFHS) diet for 2 months (T2DM model; confirmed through a GTT) and subcutaneously injected with B16F0 melanoma cells. After a 1-week or 2-week incubation period, the tumor was extracted to examine its size, weight, vascularity, and gene/protein expression. In vitro studies were performed using endothelial cells to assess the effects of high-glucose on endothelial cell proliferation, migration, and tube formation. GLRX expression was examined in both tumor samples and endothelial cells. RESULTS: The results of the study showed that T2DM induced by a HFHS diet is able to promote tumor growth in both weight (2-week, p = 0.0070) and volume (1-week, p = 0.0351; 2-week, p = 0.0002). Tumors extracted from the HFHS diet group showed reduced expressions of angiogenic markers (ACTA2 (1-week, p = 0.0239; 2-week, p = 0.0123), KDR (1-week, p = 0.0091)) by western blot and a slightly reduced trend of angiogenesis (PECAM1) in histological analyses. GLRX expression was reduced in HFHS tumor samples (1-week, p = 0.0090) and, interestingly, lower amounts of GSH adducts (2-week, p = 0.0317) could be seen in 2-week tumors as well. In vitro studies of endothelial cells showed reduced trends of endothelial cell function (proliferation, migration, and tube formation) in high glucose medium. Also, it has been observed that high glucose may be able to stimulate GLRX expression in endothelial cells. CONCLUSION: The results of the following study have confirmed that B16F0 melanoma growth is, in fact, augmented in diet-induced diabetic mice; however, the vascularity and levels of angiogenic markers from the tumor tissues did not parallel the growth in its size. In vitro studies suggested that high glucose can impair EC function (i.e. proliferation, migration, and tube formation capabilities) as well as promote GLRX expression, which may be related to this discrepancy. Glutaredoxin-1 (GLRX), an enzyme which controls redox signaling, is upregulated in DM. Endothelial cell-specific GLRX overexpression in transgenic mice was found to stimulate subcutaneously injected melanoma (B16F0) growth, despite hindering limb revascularization after hind limb ischemia. The augmented tumor progression in DM may be associated with GLRX upregulation, alongside impaired ischemic limb revascularization and tumor angiogenesis; however, the mechanism of tumor growth in diabetes still lies inconclusive and further studies need to be examined to elucidate this phenomenon

Multilevel functional principal component analysis

The Sleep Heart Health Study (SHHS) is a comprehensive landmark study of sleep and its impacts on health outcomes. A primary metric of the SHHS is the in-home polysomnogram, which includes two electroencephalographic (EEG) channels for each subject, at two visits. The volume and importance of this data presents enormous challenges for analysis. To address these challenges, we introduce multilevel functional principal component analysis (MFPCA), a novel statistical methodology designed to extract core intra- and inter-subject geometric components of multilevel functional data. Though motivated by the SHHS, the proposed methodology is generally applicable, with potential relevance to many modern scientific studies of hierarchical or longitudinal functional outcomes. Notably, using MFPCA, we identify and quantify associations between EEG activity during sleep and adverse cardiovascular outcomes.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS206 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

A savings subsidization system in a model of endogenous fertility and endogenous growth: an extension of Wigger (1999)

Population ageing is now an established demographic characteristic of many economies. Economists working in the endogenous growth theory tradition have sought to model the relationship between public pensions, financed on a 'Pay-As-You-Go' basis, and the growth in per capita incomes. The resultant intergenerational wealth redistribution from young to older people seems to decrease private savings, diminish capital accumulation, and lower the growth of per capita incomes. The underlying transmission mechanism appears to be a crowding out effect in private capital markets contingent upon the introduction of public pension systems. A growing literature exists on the interrelationships between public pension schemes, fertility rates and endogenous growth. Following Wigger's (1999) pioneering overlapping generations endogenous growth model, we extend this model to examine the effects of a savings subsidisation system on the rate of per capita income growth, fertility and voluntary intrafamily wealth transfers, where parents view children both as an insurance good and a consumption good. Moreover, children care about the consumption levels of their parents. An increase in contributions to a savings subsidised public pension scheme will crowd out private intergenerational transfers from the young to the old and thereby negate the usefulness of children as an insurance good

Multicast in wireless erasure networks with feedback

This paper studies the lossy, wireless packet network of [1], in the case of a multicast requirement and the availability of feedback. In the unicast case, feedback is sufficient to allow a strategy which achieves the throughput-optimal cut-set capacity without requiring network coding [3]. We provide a counter-example to show that source coding and feedback, without network coding, is insufficient to achieve the cut-set capacity for the multicast wireless erasure network. In particular, we examine a network with one source, one relay, and two destinations. We show that even with the highly optimistic assumption of feedback which provides global packet state awareness, this network still fails to reach capacity. This bridges the gap between two previously known results; one, that network coding can achieve the capacity of the wireless erasure network, and two, that feedback allows a capacity achieving scheme which does not require network coding in the unicast wireless erasure network

Expression of axonal protein degradation machinery in sympathetic neurons is regulated by nerve growth factor

Deficiencies in protein degradation and proteolytic function within neurons are linked to a number of neurodegenerative diseases and developmental disorders. Compartmentalized cultures of peripheral neurons were used to investigate the properties and relative abundance of the proteolytic machinery in the axons and cell bodies of sympathetic and sensory neurons. Immunoblotting of axonal proteins demonstrated that LAMP2, LC3, and PSMA2 were abundant in axons, suggesting that lysosomes, autophagosomes and proteasomes were located in axons. Interestingly, the expression of proteins associated with lysosomes and proteasomes were upregulated selectively in axons by NGF stimulation of the distal axons of sympathetic neurons, suggesting that axonal growth and maintenance requires local protein turnover. The regulation of the abundance of both proteasomes and lysosomes in axons by NGF provides a link between protein degradation and the trophic status of peripheral neurons. Inhibition of proteasomes located in axons resulted in an accumulation of ubiquitinated proteins in these axons. In contrast, lysosome inhibition in axons did not result in an accumulation of ubiquitinated proteins or the transferrin receptor, a transmembrane protein degraded by lysosomes. Interestingly, lysosomes were transported both retrogradely and anterogradely, so it is likely that ubiquitinated proteins that are normally destined for degradation by lysosomes in axons can be transported to the cellbodies for degradation. In summary, proteasomal degradation occurs locally, whereas proteins degraded by lysosomes can most likely either be degraded locally in axons or be transported to cell bodies for degradation. © 2012 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91359/1/23041_ftp.pd

Dechlorination Apparatus For Treating Chloride Salt Wastes: System Evaluation And Scale-Up

This paper describes an apparatus used to remove chlorine from chloride salt-based nuclear wastes from electrochemical reprocessing and/or chloride-based molten salt reactors (MSRs) through dechlorination by reacting the salts with ammonium dihydrogen phosphate (NH4H2PO4 or ADP) at temperatures up to 600 °C to produce NH4Cl as a byproduct. The benefits of removing the Cl from these salts include 37Cl recovery from Cl-based MSR salts, formation of UCl3 from the NH4Cl, as well as removal of Cl from the salts and conversion of the salt cations to oxides to allow for immobilization in a chemically durable iron phosphate waste form. This generation-2 system is an improvement over the generation-1 system and provides a means for scaling up salt throughput as well as NH4Cl recovery. The generation-2 system includes a five-zone furnace so the temperature of the four-zone gradient furnace can be tailored to control the location of NH4Cl condensation on a four-piece fused quartz off-gas system. Both ADP and NH4Cl decomposition reactions include the production of NH3 and acids (i.e., H3PO4 and HCl, respectively), so careful temperature control is needed during the ADP-salt reactions to maximize the NH4Cl production and minimize NH4Cl decomposition. In two sets of experiments run in the generation-1 and generation-2 apparatuses, NH4Cl yields were ≥5.5-fold higher for the new system compared to the original prototype system and the batch sizes can be ≥2.5-fold higher. In addition, some thermodynamic experiments evaluating the reactions of ADP + KCl as well as decomposition of pure NH4Cl were performed to assess the temperatures of the reactions and identify off-gas products

Validation of Different Combination of Three Reversing Half-Hitches Alternating Posts (RHAPs) Effects on Arthroscopic Knot Integrity

Introduction. With arthroscopic techniques being used, the importanceof knot tying has been examined. Previous literaturehas examined the use of reversing half-hitches on alternatingposts (RHAPs) on knot security. Separately, there has been researchregarding different suture materials commonly used inthe operating room. The specific aim of this study was to validatethe effect of different stacked half-hitch configuration anddifferent braided suture materials on arthroscopic knot integrity. Methods. Three different suture materials tied withfive different RHAPs in arthroscopic knots were compared.A single load-to-failure test was performed andthe mean ultimate clinical failure load was obtained. Results. Significant knot holding strength improvement wasfound when one half-hitch was reversed as compared to baselineknot. When two of the half-hitches were reversed, therewas a greater improvement with all knots having a mean ultimateclinical failure load greater than 150 newtons (N). Comparisonof the suture materials demonstrated a higher meanultimate clinical failure load when Force Fiber® was used andat least one half-hitch was reversed. Knots tied with eitherForce Fiber® or Orthocord® showed 0% chance of knot slippagewhile knots tied with FiberWire® or braided fishing linehad about 10 and 30% knot slippage chances, respectively. Conclusion. A significant effect was observed in regards to bothstacked half-hitch configuration and suture materials used onknot loop and knot security. Caution should be used with tyingthree RHAPs in arthroscopic surgery, particularly witha standard knot pusher and arthroscopic cannulas. The findingsof this study indicated the importance of three RHAPsin performing arthroscopic knot tying and provided evidenceregarding discrepancies of maximum clinical failure loads observedbetween orthopaedic surgeons, thereby leading to bettersurgical outcomes in the future. KS J Med 2017;10(2):35-39

Corporate Governance and Institutional Transparency in Emerging Markets

This paper posits that differences in corporate governance structure partly result from differences in institutional arrangements linked to business systems. We developed a new international triad of business systems: the Anglo-American, the Communitarian and the Emerging system, building on the frameworks of Choi et al. (British Academy of Management (Kynoch Birmingham) 1996, Management International Review 39, 257–279, 1999). A common factor determining the success of a corporate governance structure is the extent to which it is transparent to market forces. Such transparency is more than pure financial transparency; as it can also be based on factors such as governmental, banking and other types of institutional transparency mechanism. There may also be a choice for firms to adopt voluntary corporate disclosure in situations where mandatory disclosure is not established. The Asian financial crisis of 1997–1999 and the more recent corporate governance scandals such as Enron, Andersen and Worldcom in the United States and Ahold and Parmalat in Europe show that corporate governance and business ethics issues exist throughout the world. As an illustration we focus on Asia’s emerging1 markets, as, both in view of the pressure of globalization and taking into account the institutional arrangements peculiar to the emerging business system, these issues are important there. Particularly for those who have to find an accommodation between the corporate governance structures and disclosure standards of the Emerging system and those of the Anglo-American and Communitarian systems

Evaluating the sensitivity, reproducibility and flexibility of a method to test hard shell capsules intended for use in dry powder inhalers

Pharmaceutical tests for hard shell capsules are designed for orally administered capsules. The use of capsules in dry powder inhalers is widespread and increasing and therefore more appropriate tests are required to ensure quality and determine if these capsules are fit for purpose. This study aims to determine the flexibility, reproducibility and sensitivity of a quantitative method that is designed to evaluate the puncture characteristics of different capsule shell formulations under different climatic conditions. A puncture testing method was used to generate force displacement curves for five capsule formulations that were stored and tested at two different temperatures (5 °C and 19 °C). Force-displacement puncture profiles were reproducible for individual capsule shell formulations. The methodology was able to discriminate between capsules produced using different primary materials i.e. gelatin versus hypromellose, as well as more minor changes to capsule formulation i.e. different material grades and excipients. Reduced temperature increased the forces required for capsule puncture however further work is required to confirm its significance. Results indicate the method provides a reproducible and sensitive means of evaluating capsule puncture. Future studies should validate the methodology at different test sites, using different operators and with different capsule shell formulations