Threats and Changes Affecting Human Relationships with Wilderness: Implications for Management

For wilderness managers, the ability to recognize threats and changing conditions is vital. While these threats are typically associated with resource and social conditions, they can also be investigated relative to wilderness relationships. This paper explores how threats and changes may be affecting human relationships with wilderness and the possible implications for management. Previously, threats have been conceptualized as affecting ecosystem integrity or stakeholder values. This paper suggests these conceptualizations should be expanded to also consider the meanings and relationships attributed to wilderness. From such a lens, threats such as global climate change, wildland fire, and invasive species can dramatically influence both the wilderness landscape and the meanings associated with its character. They fundamentally alter the place in ways that conflict with personal histories and previous experiences. Thus, managers must be charged with finding ways to protect and foster these human relationships. Addressing threats to these relationships may also require managers to develop approaches that mitigate or adapt to these relationships over time. These approaches need to proactively define and protect a diversity of meanings and values to ensure ongoing human relationships with wilderness

A model-based approach to wind turbine condition monitoring using SCADA data

Modern wind turbines are complex aerodynamic, mechanical and electrical machines incorporating sophisticated control systems. Their design continues to increase in size and they are increasingly being positioned offshore where the environment is hostile and where there are limited windows of opportunity for repair and maintenance activities. Condition monitoring is essential offshore if Wind Turbines (WTs) are to achieve the high reliability necessary for sustained operation. Contemporary WT monitoring systems already provide vast amounts of data, the essential basis of condition monitoring, much of which is ignored until a fault or breakdown occurs. This paper presents a model-based approach to condition monitoring of WT bearings. The backbone of the approach is the use of a least squares algorithm for estimating the parameters of a discrete time transfer function (TF) model relating WT generator temperature to bearing temperature. The model is first fitted to data where it is known no problems exist. It is then used in predictive mode and the estimates of the bearing temperature are compared with the real measurements. The authors propose that significant discrepancies between the two are indicative of a developing problem with the bearings. The promising experimental results achieved so far indicate that the approach is viable

Effects of cIAP-1, cIAP-2 and XIAP triple knockdown on prostate cancer cell susceptibility to apoptosis, cell survival and proliferation

<p>Abstract</p> <p>Background</p> <p>Manipulating apoptotic resistance represents an important strategy for the treatment of hormone refractory prostate cancer. We hypothesised that the Inhibitor of Apoptosis (IAP) Proteins may be mediating this resistance and knockdown of cIAP-1, cIAP-2 and XIAP would increase sensitivity to apoptosis.</p> <p>Methods</p> <p>cIAP-1, cIAP-2 and XIAP where knocked down either individually or in combination using siRNA in androgen independent prostate cancer PC-3 cells as confirmed by real-time PCR and western blotting. Cells were then treated with TRAIL, Etoposide, or Tunicamycin, and apoptosis assessed by PI DNA staining. Apoptosis was confirmed with Annexin V labelling and measurement of PARP cleavage, and was inhibited using the pan-caspase inhibitor, zVAD.fmk. Clonogenic assays and assessment of ID-1 expression by western blotting were used to measure recovery and proliferation.</p> <p>Results</p> <p>PC-3 are resistant to TRAIL induced apoptosis and have elevated expression of cIAP-1, cIAP-2 and XIAP. Combined knockdown sensitised PC-3 to TRAIL induced apoptosis, but not to Etoposide or Tunicmycin, with corresponding increases in caspase activity and PARP cleavage which was inhibited by ZVAD.fmk. Triple knock down decreased proliferation which was confirmed by decreased ID-1 expression.</p> <p>Conclusion</p> <p>Simultaneous knock down of the IAPs not only sensitised the PC-3 to TRAIL but also inhibited their proliferation rates and clonogenic survival. The inability to alter sensitivity to other triggers of apoptosis suggests that this effect is specific for death receptor pathways and knock down might facilitate immune-surveillance mechanisms to counter cancer progression and, in combination with therapeutic approaches using TRAIL, could represent an important treatment strategy.</p

Temperate propolis has anti-inflammatory effects and is a potent inhibitor of nitric oxide formation in macrophages

Previous research has shown that propolis has immunomodulatory activity. Extracts from two UK propolis samples were assessed for their anti-inflammatory activities by investigating their ability to alter the production of the cytokines: tumour necrosis factor-ff (TNF-ff), interleukin-1 (IL-1), IL-6, and IL-10 from mouse bone marrow-derived macrophages co-stimulated with lipopolysaccharide (LPS). The propolis extracts suppressed the secretion of IL-1 and IL-6 with less effect on TNFff. In addition, propolis reduced the levels of nitric oxide formed by LPS-stimulated macrophages. Metabolomic profiling was carried out by liquid chromatography (LC) coupled with mass spectrometry (MS) on a ZIC-pHILIC column. LPS increased the levels of intermediates involved in nitric oxide biosynthesis; propolis lowered many of these. In addition, LPS produced an increase in itaconate and citrate, and propolis treatment increased itaconate still further while greatly reducing citrate levels. Moreover, LPS treatment increased levels of glutathione (GSH) and intermediates in its biosynthesis, while propolis treatment boosted these still further. In addition, propolis treatment greatly increased levels of uridine diphosphate (UDP)-sugar conjugates. Overall, the results showed that propolis extracts exert an anti-inflammatory effect by the inhibition of pro-inflammatory cytokines and by the metabolic reprogramming of LPS activity in macrophages

Augmented intracellular glutathione inhibits fas-triggered apoptosis of activated human neutrophils

Q1Q1Agonist signals delivered through cell surface Fas induce apoptosis. However, the apoptotic program can be modulated by signals from the environment, and in particular, by signals delivered through adhesion molecules. Because neutrophil functional activity in inflammation is contingent on cell survival, and because circulating neutrophils normally die rapidly through a constitutively expressed apoptotic program, we evaluated Fas-mediated apoptosis in resting and inflammatory human neutrophils. We show that normal neutrophils respond to Fas engagement with accelerated rates of apoptosis, but cross-linking of β2 integrins or priming with bacterial lipopolysaccharide (LPS) prevents this increase. Adhesion molecule cross-linking results in increased intracellular glutathione (GSH). Augmentation of intracellular GSH with exogenous GSH or N-acetylcysteine is sufficient to reduce the Fas-triggered increase in apoptotic rates. Prevention of the activation induced GSH increase by buthionine sulfoximine, a cell permeable inhibitor of GSH biosynthesis, restored Fas responsiveness in activated neutrophils, an effect that could be blocked with exogenous GSH. Taken together, these data show that Fas-induced signaling for neutrophil apoptosis is blocked in a redox sensitive manner by costimulatory signals delivered through β2 integrins or activation by LPS, and provide a biologic explanation for sustained neutrophil survival in the inflammatory environment.Revista Nacional - Indexad

The discovery of 2.78 hour periodic modulation of the X-ray flux from globular cluster source Bo 158 in M31

We report the discovery of periodic intensity dips in the X-ray source XMMU J004314.1+410724, in the globular cluster Bo158 in M31. The X-ray flux was modulated by ~83% at a period of 2.78 hr (10017 s) in an XMM-Newton observation taken 2002 Jan 6-7. The X-ray intensity dips show no energy dependence. We detected weaker dips with the same period in observations taken 2000 June 25 (XMM-Newton) and 1991 June 26 (ROSAT/PSPC). The amplitude of the modulation has been found to be anticorrelated with source X-ray flux: it becomes lower when the source intensity rises. The energy spectrum of Bo158 was stable from observation to observation, with a characteristic cutoff at ~4-6 keV. The photo-electric absorption was consistent with the Galactic foreground value. No significant spectral changes were seen in the course of the dips. If the 2.78 hr cycle is the binary period of Bo158 the system is highly compact, with a binary separation of ~10e11 cm. The association of the source with a globular cluster, together with spectral parameters consistent with Galactic neutron star sources, suggests that X-rays are emitted by an accreting neutron star. The properties of Bo 158 are somewhat reminiscent of the Galactic X-ray sources exhibiting a dip-like modulations. We discuss two possible mechanisms explaining the energy-independent modulation observed in Bo 158: i) the obscuration of the central source by highly ionized material that scatters X-rays out of the line of sight; ii) partial covering of an extended source by an opaque absorber which occults varying fractions of the source.Comment: 10 pages, 4 figures, ApJ, submitted, uses emulateapj styl

The Apoptosome Pathway to Caspase Activation in Primary Human Neutrophils Exhibits Dramatically Reduced Requirements for Cytochrome c

Caspase activation is a central event in numerous forms of apoptosis and results in the proteolytic degradation of multiple substrate proteins that contribute to the apoptotic phenotype. An important route to caspase activation proceeds via assembly of the “apoptosome” as a result of the cell stress–associated release of mitochondrial cytochrome c. Previous studies have shown that primary neutrophils are largely incapable of mitochondrial respiration, suggesting that these cells either lack functional mitochondria or possess a defective respiratory chain. This prompted us to examine whether neutrophils retain an intact cytochrome c/apoptotic protease-activating factor 1 (Apaf-1) pathway to caspase activation and apoptosis. We show that primary human neutrophils contain barely detectable levels of cytochrome c as well as other mitochondrial proteins. Surprisingly, neutrophil cell–free extracts readily supported Apaf-1–dependent caspase activation, suggesting that these cells may assemble cytochrome c–independent apoptosomes. However, further analysis revealed that the trace amount of cytochrome c present in neutrophils is both necessary and sufficient for Apaf-1–dependent caspase activation in these cells. Thus, neutrophils have a lowered threshold requirement for cytochrome c in the Apaf-1–dependent cell death pathway. These observations suggest that neutrophils retain cytochrome c for the purpose of assembling functional apoptosomes rather than for oxidative phosphorylation