Corticotropin-releasing hormone interacts with interleukin-1 to regulate prostaglandin H synthase-2 expression in human myometrium during pregnancy and labor

Context: The onset of labor appears to involve the activation of myometrial inflammatory pathways, and transcription factors such as nuclear factor-κB (NF-κB) control expression of the contraction-associated proteins required to induce a procontractile phenotype. These responses might involve CRH, which integrates immune and neuroendocrine systems. Objectives: In human myometrium we investigated cyclooxygenase 2 (PGHS2) expression and regulation by CRH and the proinflammatory cytokine IL-1β before and after labor. Design: Myometrial tissues obtained from pregnant women at term before (n = 12) or during labor (n = 10) and pathological cases of choriamnionitis-associated term labor (n = 5) were used to isolate primary myocytes and investigate in vitro, CRH effects on basal and IL-1β regulated p65 activation and PGHS2 expression. Results: In nonlaboring myometrial cells, CRH was unable to induce NF-κB nuclear translocation; however, it altered the temporal dynamics of IL-1β-driven NF-κB nuclear entry by initially delaying entry and subsequently prolonging retention. These CRH-R1-driven effects were associated with a modest inhibitory action in the early phase (within 2 hours) of IL-1β stimulated PGHS2 mRNA expression, whereas prolonged stimulation for 6–18 hours augmented the IL-1β effects. The early-phase effect required intact protein kinase A activity and was diminished after the onset of labor. The presence of chorioamnionitis led to exaggerated PGHS2 mRNA responses to IL-1β but diminished effects of CRH. Conclusions: CRH is involved in the inflammatory regulation of PGHS2 expression before and during labor; these actions might be important in priming and preparing the myometrium for labor and cellular adaptive responses to inflammatory mediator

Achieving Optimal Throughput and Near-Optimal Asymptotic Delay Performance in Multi-Channel Wireless Networks with Low Complexity: A Practical Greedy Scheduling Policy

In this paper, we focus on the scheduling problem in multi-channel wireless networks, e.g., the downlink of a single cell in fourth generation (4G) OFDM-based cellular networks. Our goal is to design practical scheduling policies that can achieve provably good performance in terms of both throughput and delay, at a low complexity. While a class of $O(n^{2.5} \log n)$-complexity hybrid scheduling policies are recently developed to guarantee both rate-function delay optimality (in the many-channel many-user asymptotic regime) and throughput optimality (in the general non-asymptotic setting), their practical complexity is typically high. To address this issue, we develop a simple greedy policy called Delay-based Server-Side-Greedy (D-SSG) with a \lower complexity $2n^2+2n$, and rigorously prove that D-SSG not only achieves throughput optimality, but also guarantees near-optimal asymptotic delay performance. Specifically, we show that the rate-function attained by D-SSG for any delay-violation threshold $b$, is no smaller than the maximum achievable rate-function by any scheduling policy for threshold $b-1$. Thus, we are able to achieve a reduction in complexity (from $O(n^{2.5} \log n)$ of the hybrid policies to $2n^2 + 2n$) with a minimal drop in the delay performance. More importantly, in practice, D-SSG generally has a substantially lower complexity than the hybrid policies that typically have a large constant factor hidden in the $O(\cdot)$ notation. Finally, we conduct numerical simulations to validate our theoretical results in various scenarios. The simulation results show that D-SSG not only guarantees a near-optimal rate-function, but also empirically is virtually indistinguishable from delay-optimal policies.Comment: Accepted for publication by the IEEE/ACM Transactions on Networking, February 2014. A preliminary version of this work was presented at IEEE INFOCOM 2013, Turin, Italy, April 201

From GRID to gridlock: the relationship between scientific biomedical breakthroughs and HIV/AIDS policy in the US Congress

Introduction: From the travel ban on people living with HIV (PLHIV) to resistance to needle exchange programmes, there are many examples where policy responses to HIV/AIDS in the United States seem divorced from behavioural, public health and sociological evidence. At its root, however, the unknowns about HIV/AIDS lie at biomedical science, and scientific researchers have made tremendous progress over the past 30 years of the epidemic by using antiretroviral therapy to increase the life expectancy of PLHIV almost to the same level as non-infected individuals; but a relationship between biomedical science discoveries and congressional responses to HIV/AIDS has not been studied. Using quantitative approaches, we directly examine the hypothesis that progress in HIV/AIDS biomedical science discoveries would have a correlative relationship with congressional response to HIV/AIDS from 1981 to 2010. Methods: This study used original data on every bill introduced, hearing held and law passed by the US Congress relating to HIV/AIDS over 30 years (1981–2010). We combined congressional data with the most cited and impactful biomedical research scientific publications over the same time period as a metric of biomedical science breakthroughs. Correlations between congressional policy and biomedical research were then analyzed at the aggregate and individual levels. Results: Biomedical research advancements helped shape both the level and content of bill sponsorship on HIV/AIDS, but they had no effect on other stages of the legislative process. Examination of the content of bills and biomedical research indicated that science helped transform HIV/AIDS bill sponsorship from a niche concern of liberal Democrats to a bipartisan coalition when Republicans became the majority party. The trade-off for that expansion has been an emphasis on the global epidemic to the detriment of domestic policies and programmes. Conclusions: Breakthroughs in biomedical science did associate with the number and types of HIV/AIDS bills introduced in Congress, but that relationship did not extend to the passage of laws or to hearings. When science matters, it cannot be separated from political considerations. An important implication of our work has been the depoliticizing role that science can play. Scientific breakthroughs helped to transform HIV/AIDS policy from a niche of liberal Democrats into bipartisan support for the global fight against the disease

Solitons in finite droplets of noncommutative Maxwell-Chern-Simons theory

We find soliton solutions of the noncommutative Maxwell-Chern-Simons theory confined to a finite quantum Hall droplet. The solitons are exactly as hypothesized in \cite{Manu}. We also find new variations on these solitons. We compute their flux and their energies. The model we consider is directly related to the model proposed by Polychronakos\cite{Poly} and studied by Hellerman and Van Raamsdonk\cite{HvR} where it was shown that it is equivalent to the quantum Hall effect.Comment: 18 pages, 7 figures, minor corrections, version accepted for publication, this time really

Investigation of concrete produced using recycled aluminium dross for hot weather concreting conditions

Aluminium dross is a by-product obtained from the aluminium smelting process. Currently, this dross is processed in rotary kilns to recover the residual aluminium, and the resultant salt cake is sent to landfills. The present study investigates the utilization of recycled aluminium dross in producing concrete, which is suitable for hot weather concreting condition. The primary objectives of the experimental study are to examine the feasibility of using concrete blended with recycled aluminium dross under hot weather concreting situations and then to evaluate the strength and durability aspects of the produced concrete. From the experimental results it is observed that the initial setting time of the recycled aluminium dross concrete extended by about 30 minutes at 20% replacement level. This property of recycled aluminium dross concrete renders it to be suitable for hot weather concreting conditions. Based on the results obtained, the replacement of cement with 20% of Al dross yields superior mechanical and durability characteristics

Decreased soluble guanylate cyclase contributes to cardiac dysfunction induced by chronic doxorubicin treatment in mice

Aims: The use of doxorubicin, a potent chemotherapeutic agent, is limited by cardiotoxicity. We tested the hypothesis that decreased soluble guanylate cyclase (sGC) enzyme activity contributes to the development of doxorubicin-induced cardiotoxicity. Results: Doxorubicin administration (20 mg/kg, intraperitoneally [IP]) reduced cardiac sGC activity in wild-type (WT) mice. To investigate whether decreased sGC activity contributes to doxorubicin-induced cardiotoxicity, we studied mice with cardiomyocyte-specific deficiency of the sGC alpha 1-subunit (mice with cardiomyocyte-specific deletion of exon 6 of the sGC alpha 1 allele [sGC alpha 1(-/-CM)]). After 12 weeks of doxorubicin administration (2 mg/kg/week IP), left ventricular (LV) systolic dysfunction was greater in sGC alpha 1(-/-CM) than WT mice. To further assess whether reduced sGC activity plays a pathogenic role in doxorubicin-induced cardiotoxicity, we studied a mouse model in which decreased cardiac sGC activity was induced by cardiomyocyte-specific expression of a dominant negative sGC alpha 1 mutant (DNsGC alpha 1) upon doxycycline removal (Tet-off). After 8 weeks of doxorubicin administration, DNsGC alpha 1(tg/+), but not WT, mice displayed LV systolic dysfunction and dilatation. The difference in cardiac function and remodeling between DNsGC alpha 1(tg/+) and WT mice was even more pronounced after 12 weeks of treatment. Further impairment of cardiac function was attenuated when DNsGC alpha 1 gene expression was inhibited (beginning at 8 weeks of doxorubicin treatment) by administering doxycycline. Furthermore, doxorubicin-associated reactive oxygen species generation was higher in sGC alpha 1-deficient than WT hearts. Innovation and Conclusion: These data demonstrate that a reduction in cardiac sGC activity worsens doxorubicin-induced cardiotoxicity in mice and identify sGC as a potential therapeutic target. Various pharmacological sGC agonists are in clinical development or use and may represent a promising approach to limit doxorubicin-associated cardiotoxicity

The Role of Regulated mRNA Stability in Establishing Bicoid Morphogen Gradient in Drosophila Embryonic Development

The Bicoid morphogen is amongst the earliest triggers of differential spatial pattern of gene expression and subsequent cell fate determination in the embryonic development of Drosophila. This maternally deposited morphogen is thought to diffuse in the embryo, establishing a concentration gradient which is sensed by downstream genes. In most model based analyses of this process, the translation of the bicoid mRNA is thought to take place at a fixed rate from the anterior pole of the embryo and a supply of the resulting protein at a constant rate is assumed. Is this process of morphogen generation a passive one as assumed in the modelling literature so far, or would available data support an alternate hypothesis that the stability of the mRNA is regulated by active processes? We introduce a model in which the stability of the maternal mRNA is regulated by being held constant for a length of time, followed by rapid degradation. With this more realistic model of the source, we have analysed three computational models of spatial morphogen propagation along the anterior-posterior axis: (a) passive diffusion modelled as a deterministic differential equation, (b) diffusion enhanced by a cytoplasmic flow term; and (c) diffusion modelled by stochastic simulation of the corresponding chemical reactions. Parameter estimation on these models by matching to publicly available data on spatio-temporal Bicoid profiles suggests strong support for regulated stability over either a constant supply rate or one where the maternal mRNA is permitted to degrade in a passive manner

On plane wave and vortex-like solutions of noncommutative Maxwell-Chern-Simons theory

We investigate the spectrum of the gauge theory with Chern-Simons term on the noncommutative plane, a modification of the description of the Quantum Hall fluid recently proposed by Susskind. We find a series of the noncommutative massive ``plane wave'' solutions with polarization dependent on the magnitude of the wave-vector. The mass of each branch is fixed by the quantization condition imposed on the coefficient of the noncommutative Chern-Simons term. For the radially symmetric ansatz a vortex-like solution is found and investigated. We derive a nonlinear difference equation describing these solutions and we find their asymptotic form. These excitations should be relevant in describing the Quantum Hall transitions between plateaus and the end transition to the Hall Insulator.Comment: 17 pages, LaTeX (JHEP), 1 figure, added references, version accepted to JHE