47 research outputs found
Organometallic ruthenium-based antitumor compounds with novel modes of action
No full text10.1016/j.jorganchem.2010.11.009Journal of Organometallic Chemistry6965989-998JORC
Lifecycle Impacts of the Financial and Economic Crisis on Household Optimal Consumption, Portfolio Choice, and Labor Supply
Full text linkThe direct financial impact of the financial crisis has been to deal a heavy blow to investment-based pensions; many workers lost a substantial portion of their retirement saving. The financial sector implosion in turn produced an economic crisis for the rest of the economy via high unemployment and reduced labor earnings, which reduced contributions to Social Security and private pensions. Our research asks which types of individuals were most affected by these dual financial and economic shocks, and it also explores how people may react by changing their consumption, saving and investment, work and retirement, and annuitization decisions. We do so with a realistically calibrated lifecycle framework allowing for time-varying investment opportunities and countercyclical risky labor income dynamics. We show that households near retirement will reduce both short- and long-term consumption, boost work effort, and defer retirement. Younger cohorts will initially reduce their work hours, consumption, saving, and equity exposure; later in life, they will have to work more, retire later, consume less, invest more in stocks, and save more.Social Security Administrationhttp://deepblue.lib.umich.edu/bitstream/2027.42/87952/1/wp246.pd
Urotensin II Stimulates Vascular Endothelial Growth Factor Secretion From Adventitial Fibroblasts in Synergy With Angiotensin II
No full textBackground: The adventitia plays an important role in and is considered to be the initiating site for vascular remodeling. Urotensin II (UII) and angiotensin II (Ang II) are the two most important vascular peptides involved in vascular remodeling in the adventitia. Nevertheless, little is known about their effect on the expression of vascular endothelial growth factor (VEGF). It was hypothesized that both UII and Ang II could induce VEGF expression in adventitial fibroblasts and VEGF may play a role in cell proliferation and collagen I synthesis induced by UII or Ang II. Methods and Results: Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII and/or Ang II and inhibitors of the mitogen-activated protein kinase (MAPK) pathway or VEGF-neutralizing antibodies. The VEGF expression was evaluated using enzyme-linked immunosorbent assay (ELISA), while the proliferation and collagen I synthesis were detected using methyl thiazol tetrazolium (MU) assay and ELISA. It was found that: (1) both UII and Ang II could stimulate VEGF expression in adventitial fibroblasts and they had a synergistic effect; (2) MAPK pathway inhibitors could inhibit VEGF secretion induced by UII and/or Ang II; and (3) VEGF-neutralizing antibodies could inhibit UII/Ang II-induced cell proliferation and collagen synthesis in adventitial fibroblasts. Conclusions: Induction of VEGF expression may be a new mechanism involved in vascular remodeling for UII and Ang II. (Circ J 2012; 76: 1267-1273)http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000303369800033&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Cardiac & Cardiovascular SystemsSCI(E)1451267-12737
Chordal-NMF with Riemannian Multiplicative Update
Full text linkNonnegative Matrix Factorization (NMF) is the problem of approximating a
given nonnegative matrix M through the conic combination of two nonnegative
low-rank matrices W and H. Traditionally NMF is tackled by optimizing a
specific objective function evaluating the quality of the approximation. This
assessment is often done based on the Frobenius norm. In this study, we argue
that the Frobenius norm as the "point-to-point" distance may not always be
appropriate. Due to the nonnegative combination resulting in a polyhedral cone,
this conic perspective of NMF may not naturally align with conventional
point-to-point distance measures. Hence, a ray-to-ray chordal distance is
proposed as an alternative way of measuring the discrepancy between M and WH.
This measure is related to the Euclidean distance on the unit sphere,
motivating us to employ nonsmooth manifold optimization approaches.
We apply Riemannian optimization technique to solve chordal-NMF by casting it
on a manifold. Unlike existing works on Riemannian optimization that require
the manifold to be smooth, the nonnegativity in chordal-NMF is a
non-differentiable manifold. We propose a Riemannian Multiplicative Update
(RMU) that preserves the convergence properties of Riemannian gradient descent
without breaking the smoothness condition on the manifold.
We showcase the effectiveness of the Chordal-NMF on synthetic datasets as
well as real-world multispectral images.Comment: 32 pages, 7 figures, 3 tables. arXiv admin note: text overlap with
arXiv:1907.02404 by other author
Yes/no questions in mandarin chinese revisited
No full textThis article discusses some syntactic peculiarities of Chinese yes/no questions. Starting from the observation that Standard Mandarin shares significant typological features with prototypical SOV languages, Chinese is treated as an underlyingly verb-final language. Based on this heuristic principle, A-not-AB, AB-not-A and AB-not questions are uniformly derived by means of one simple raising rule that operates within the sentence constituent V'. This novel idea is elaborated on in great detail in the first part of the article. In contrast to the prevailing trend, it is argued that the question operator contained in A-not-A and A-not sentences CANNOT be raised to "Comp". In consequence, A-not-A and A-not questions are "typed" in the head position of a sentence-internal functional phrase that we call Force2 Phrase (F2P) in the present paper. This position is not to be confused with Drubig's (1994) Polarity 1 Phrase (PollP), in the head position of which assertive negations and an abstract affirmative element are located. The existence of a head position F2° other than Poll° is supported by the fact that F2° can be occupied by certain overt question operators, such as assertive shi-bu-shi, which are compatible with negations. In contrast to the assertive question operator shi-bu-shi which is obligatorily associated with information focus, non-assertive shi-bu-shi serves as a compound focus and question operator whose focus feature is complex insofar as it is composed of two subfeatures: a contrastivity and an exhaustivity subfeature. Non-assertive shi-bu-shi is obligatorily associated with identificational focus in the sense of Kiss (1998). In accordance with some basic ideas of Chomsky's checking theory, the two subfeatures of the complex focus feature carried by the non-assertive shi-bu-shi operator check a correlating subfeature in the head position of a corresponding functional phrase (Contrastive Phrase and Focus Phrase, respectively). The question feature contained in the non-assertive shi-bu-shi operator is attracted by the head of Force1 Phrase (F1') at the level of LF. Due to the fact that F1° is sentence-final, the question feature of non-assertive shi-bu-shi must be Chomsky-adjoined to F1'. Unlike identificational focus phrases which are inherently contrastive, topics are non-contrastive in the default case. As separate speech acts, they are located in a c-commanding position outside the sentence structure. Semantically, there is a difference between Frame-Setting Topics and Aboutness Topics. As shown in the article, both A-not-A and A-not questions on the one hand and yes/no questions ending with ma on the other can be used in neutral and non-neutral contexts. The decisive advantage of mu questions, however, is that their question operator has scope over the whole sentence
Seamless pressure-deficient water distribution system model
No full textPressure-deficient conditions are a common occurrence in water distribution systems. These situations require accurate modelling for timely decision making. However, the conventional demand-driven analysis approach to network modelling is unsuitable for operating conditions with insufficient pressure. Increasing emphasis is being placed on the need for water companies to satisfy stringent performance standards for the continuous supply of water to consumers and it is those pressure-deficient operating conditions which are critical in determining whether or not adequate supplies can be provided. It is therefore very unfortunate that the demand-driven analysis method becomes invalid for use in precisely those critical conditions. The aim of this paper is to present a new pressure-dependent demand function to help improve the simulation of pressure-deficient conditions. The proposed function has better computational properties than those in the literature and has been incorporated successfully in the governing equations for water distribution networks. In particular, the proposed function and its derivative do not have the discontinuities that often cause convergence difficulties in the solution of the constitutive equations. A robust Newton–Raphson algorithm was developed to model water distribution systems under both normal and pressure-deficient conditions in a seamless way. Examples which demonstrate the methodology are included
Lack of direct evidence for a functional role of voltage-operated calcium channels in juxtaglomerular cells
Full text linkIn this study we have examined the role of voltage-gated calcium channels in the regulation of calcium in juxtaglomerular cells. Using a combination of patch-clamp and single-cell calcium measurement we obtained evidence neither for voltage-operated calcium currents nor for changes of the intracellular calcium concentration upon acute depolarizations of the cell membrane. Increases of the extracellular concentration of potassium to 80 mmol/l depolarized the juxtaglomerular cells close to the potassium equilibrium potential, but did not alter the intracellular calcium concentration neither in patch-clamped nor in intact Furaester-loaded cells. Moreover, basal renin secretion from a preparation enriched in mouse juxtaglomerular cells and from rat glomeruli with attached juxtaglomerular cells was not inhibited when extracellular potassium was isoosmotically increased to 56 mmol/l. In mouse kidney slices, however, depolarizing potassium concentrations caused a delayed inhibition at 56 mmol/l and a delayed stimulation of renin secretion at 110 mmol/l. Taken together, our study does not provide direct evidence for a role of voltage-activated calcium channels in the regulation of calcium and renin secretion in renal juxtaglomerular cells
Minbar al-Sharq, No.246 (vol. 22, Mar. 26, 1943)
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The development of contraceptive vaccines
No full textThe use of vaccination as a means of controlling fertility was established during the last decade with the publication of a successful Phase II trial demonstrating the efficacy of this approach to family planning. However, only this one Phase II trial has been completed despite a plethora of hormonal and gamete antigens that have been proposed as candidate vaccines. Improvements in the design and formulation of contraceptive vaccines are underway and will be a necessary prelude to further clinical trials
Translational research in rheumatoid arthritis: Exploiting melanocortin receptors
Full text linkThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the authorRheumatoid arthritis (RA) is a chronic inflammatory disease affecting 1% of the population. The aetiology of rheumatoid arthritis is unknown, although there are multiple postulated theories. In 1950, Philip Hench won the Nobel prize for treating patients with rheumatoid arthritis with cortisone. He also treated 6 patients with adrenocorticotropic hormone (ACTH) with good results. ACTH is a melanocortin. The melanocortin system describes the five melanocortin receptors, their ligands, agonists and antagonists and the accessory proteins. The aim of this study was to explore the melanocortin receptors in rheumatoid arthritis synovium.
Methods
HA-tagged stable cell lines were created for MC1R, MC3R and MC5R. Multiple antibodies were tested for their utility using Western Blot, immunohistochemistry and flow cytometry. Samples of synovium from 28 patients with RA were tested using RTPCR for the presence of MC1R and MC3R. Gene expression was correlated with clinical characteristics, cytokine (RTPCR) expression and immunohistochemical score.
Results
The stable cell lines expressed MC1R, MC3R and MC5R respectively. Of the antibodies tested none were found to be of utility in detecting MC1R or MC3R .The MC1R RQ values in rheumatoid synovium appear to split into two groups, high and low. The medians of the two groups are significantly different (p=0.0005). There is almost a 5 cycle, or 64 fold, difference in gene expression between the medians of the two groups (1.59 v 6.23). Of note no MC3R positive samples were CD138 high (i.e. no MC3R positive samples had a significant plasma cell infiltrate) (p=0.006). Categorical analysis using Fishers Exact test revealed an association between MC1R high samples and CD68 lining high scores, (i.e. MC1R high samples also had a high macrophage score in the lining of the sample) (p=0.02). MC1R low samples were associated with not being on combination therapy,
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this did not quite reach significance (p=0.07). Linear regression analysis confirmed these associations for MC1R. PCA analysis did not show any grouping of samples according to any of the variables tested, likely due to sample size.
Conclusion
MC1R and MC3R are found in human synovium. Current commercial antibodies are not of utility in detecting MC1R or MC3R. Synovial samples can be split into high and low MC1R gene expression groups. MC3R was either present or absent. High expression of MC1R was associated with a high macrophage score and MC3R expression was associated with a low plasma cell score. MC1R and MC3R expression in RA synovium could be used as biomarkers of disease state or severity as well as a target for therapy
