The Air Littoral: Another Look

Assessing threats to the air littoral, the airspace between ground forces and high-end fighters and bombers, requires a paradigm change in American military thinking about verticality. This article explores the consequences of domain convergence, specifically for the Army and Air Force’s different concepts of control. It will assist US military and policy practitioners in conceptualizing the air littoral and in thinking more vertically about the air and land domains and the challenges of domain convergence

Somatostatin Is Expressed in FRTL-5 Thyroid Cells and Prevents Thyrotropin-Mediated Down-Regulation of the Cyclin-Dependent Kinase Inhibitor p27kip11

9 pages, 8 figures, 3 tables.Using RT and amplification, we have detected specific RNA transcripts encoding somatostatin in FRTL-5 thyroid cells. This observation indicates that within the thyroid context, expression of somatostatin is not restricted to the parafollicular C cells. Transfection of FRTL-5 cells with constructs containing either the complete somatostatin gene promoter or deletions carrying the cAMP response element-binding site allowed us to demonstrate that transcription of the somatostatin gene is hormonally regulated by TSH. Blockage of somatostatin by specific antibodies resulted in an increased capacity of TSH-induced FRTL-5 cell-conditioned medium to promote cell proliferation, demonstrating that under physiological conditions, somatostatin exerts a cytostatic effect on FRTL-5 cells growth. Somatostatin treatment of FRTL-5 cells resulted in a growth retardation, caused by a dose-response delay in the G1 phase of the cell cycle. This effect appears to be mediated by the cyclin-dependent kinase inhibitor p27kip1, which is clearly down-regulated in FRTL-5 cells treated with TSH and whose expression is reestablished by somatostatin in a dose-dependent manner. Participation of somatostatin in the control of FRTL-5 cell proliferation is in agreement with the detection of specific somatostatin receptor type 2. Flow cytometric assays reveal that FRTL-5 cells transformed with the K-ras oncogene are still sensitive to somatostatin treatment, whereas fully neoplastic FRT cells no longer respond to this peptide. Taking together, the results demonstrate the participation of an autocrine loop in the control of thyroid cell proliferation, and the possibility that this mechanism could be altered in the process of thyroid carcinogenesis.This work was supported by Grants DGICYT (PM97–0065), CAM (08.1/0025/1997), and Fundación Salud 2000 (Spain).Peer reviewe

Environmental Risk Factors for Pneumocystis Pneumonia Hospitalizations in HIV Patients

Background. Pneumocystis pneumonia (PcP) is the second leading cause of morbidity and mortality in human immunodeficiency virus (HIV)–infected patients in the United States. Although the host risk factors for the development of PcP are well established, the environmental (climatological, air pollution) risk factors are poorly understood. The major goal of this study was to determine the environmental risk factors for admissions of HIV-positive patients with PcP to a single medical center. / Methods. Between 1997 and 2008, 457 HIV-positive patients with microscopically confirmed PcP were admitted to the San Francisco General Hospital. A case-crossover design was applied to identify environmental risk factors for PcP hospitalizations. Climatological and air pollution data were collected from the Environmental Protection Agency and Weather Warehouse databases. Conditional logistic regression was used to evaluate the association of each environmental factor and PcP hospital admission. / Results. Hospital admissions were significantly more common in the summer than in the other seasons. Increases in temperature and sulfur dioxide levels were independently associated with hospital admissions for PcP, but the effects of sulfur dioxide were modified by increasing carbon monoxide levels. / Conclusions. This study identifies both climatological and air pollution constituents as independent risk factors for hospitalization of HIV-positive patients with PcP in San Francisco. Thus, the environmental effects on PcP are more likely complex than previously thought. Further studies are needed to understand how these factors exert their effects and to determine if these factors are associated with PcP in other geographic locations

Cooperation and Self-Regulation in a Model of Agents Playing Different Games

A simple model for cooperation between "selfish" agents, which play an extended version of the Prisoner's Dilemma(PD) game, in which they use arbitrary payoffs, is presented and studied. A continuous variable, representing the probability of cooperation, $p_k(t) \in$ [0,1], is assigned to each agent $k$ at time $t$. At each time step $t$ a pair of agents, chosen at random, interact by playing the game. The players update their $p_k(t)$ using a criteria based on the comparison of their utilities with the simplest estimate for expected income. The agents have no memory and use strategies not based on direct reciprocity nor 'tags'. Depending on the payoff matrix, the systems self-organizes - after a transient - into stationary states characterized by their average probability of cooperation $\bar{p}_{eq}$ and average equilibrium per-capita-income $\bar{p}_{eq},\bar{U}_\infty$. It turns out that the model exhibit some results that contradict the intuition. In particular, some games which - {\it a priory}- seems to favor defection most, may produce a relatively high degree of cooperation. Conversely, other games, which one would bet that lead to maximum cooperation, indeed are not the optimal for producing cooperation.Comment: 11 pages, 3 figures, keybords: Complex adaptive systems, Agent-based models, Social system

Novel anti-inflammatory and chondroprotective effects of the human melanocortin MC1 receptor agonist BMS-470539 dihydrochloride and human melanocortin MC3 receptor agonist PG-990 on lipopolysaccharide activated chondrocytes

Human melanocortin MC1 and MC3 receptors expressed on C-20/A4 chondrocytes exhibit chondroprotective and anti-inflammatory effects when activated by melanocortin peptides. Nearly 9 million people in the UK suffer from osteoarthritis, and bacterial infections play a role in its development. Here, we evaluate the effect of a panel of melanocortin peptides with different selectivity for human melanocortin MC1 (α-MSH, BMS-470539 dihydrochloride) and MC3 ([DTrp8]-γ-MSH, PG-990) receptors and C-terminal peptide α-MSH11-13(KPV), on inhibiting LPS-induced chondrocyte death, pro-inflammatory mediators and induction of anti-inflammatory proteins. C-20/A4 chondrocytes were treated with a panel of melanocortin peptides prophylactically and therapeutically in presence of LPS (0.1 μg/ml). The chondroprotective properties of these peptides determined by cell viability assay, RT-PCR, ELISA for detection of changes in inflammatory markers (IL-6, IL-8 and MMP-1, -3 and -13) and western blotting for expression of the anti-inflammatory protein heme-oxygenase-1. C-20/A4 expressed human melanocortin MC1 and MC3 receptors and melanocortin peptides elevated cAMP. LPS stimulation caused a reduction in C-20/A4 viability, attenuated by the human melanocortin MC1 receptor agonist BMS-470539 dihydrochloride, and MC3 receptor agonists PG-990 and [DTrp8]-γ-MSH. Prophylactic and therapeutic regimes of [DTrp8]-γ-MSH significantly inhibited LPS-induced modulation of cartilage-damaging IL-6, IL-8, MMPs −1,-3 and −13 mediators both prophylactically and therapeutically, whilst human melanocortin MC1 and MC3 receptor agonists promoted an increase in HO-1 production. In the presence of LPS, activation of human melanocortin MC1 and MC3 receptors provided potent chondroprotection, upregulation of anti-inflammatory proteins and downregulation of inflammatory and proteolytic mediators involved in cartilage degradation, suggesting a new avenue for osteoarthritis treatment

Spatial repellents: from discovery and development to evidence based validation

International public health workers are challenged by a burden of arthropod-borne disease that remains elevated despite best efforts in control programmes. With this challenge comes the opportunity to develop novel vector control paradigms to guide product development and programme implementation. The role of vector behaviour modification in disease control was first highlighted several decades ago but has received limited attention within the public health community. This paper presents current evidence highlighting the value of sub-lethal agents, specifically spatial repellents, and their use in global health, and identifies the primary challenges towards establishing a clearly defined and recommended role for spatial repellent products in disease control

Highly efficient synthesis of the tricyclic core of Taxol by cascade metathesis

An efficient enantioselective synthesis of the ABC tricyclic core of the anticancer drug Taxol is reported. The key step of this synthesis is a cascade metathesis reaction, which leads in one operation to the required tricycle if appropriate fine-tuning of the dienyne precursor is performed