Harvard College OSO-IV pointed experiment - An analysis of the malfunction during orbit 637

Telemetered malfunction data analysis from orbiting OSO- 4 implicating transforme

Reconstruction of environmental histories to investigate patterns of larval radiated shanny (Ulvaria subbifurcata) growth and selective survival in a large bay of Newfoundland

We used otolith microstructure analysis to reconstruct the growth histories of larval radiated shanny ( Ulvaria subbifurcata ) collected over a 2-week period in Trinity Bay, Newfoundland. A dynamic 3-dimensional, eddy-resolving circulation model of the region provided larval drift patterns, which were combined with measurements of temperature and zooplankton abundance to assess the environmental history of the larvae. The abundance of juvenile and adult capelin ( Mallotus villosus ), the dominant planktivorous fish in this area, was monitored using five hydroacoustic surveys. The goal was to determine whether environmental histories are helpful in explaining spatial and temporal differences in larval shanny growth, measured as cumulative distribution functions (CDF) of growth rates. We found evidence for a selective loss of slower growing individuals and recognized considerable spatial differences in the CDF of larval growth rates. Consistent patterns in capelin abundance suggested that faster growing survivors, sampled at the end of the 2-week period, developed in areas of low predator densities. A dome-shaped relationship between temperature and larval growth was observed, explaining a significant but small amount of the overall variability (14%). Effects of experienced prey concentrations on larval growth rates could not be demonstrated

RasGRP1 Transduces Low-Grade TCR Signals which Are Critical for T Cell Development, Homeostasis, and Differentiation

AbstractTwo important Ras-guanyl nucleotide exchange factors, Sos and RasGRP1, control Ras activation in thymocytes. However, the relative contribution of these two exchange factors to Ras/ERK activation and their resulting impact on positive and negative selection is unclear. We have produced two lines of RasGRP1−/− TCR transgenic mice to determine the effect of RasGRP1 in T cell development under conditions of defined TCR signaling. Our results demonstrate that RasGRP1 is crucial for thymocytes expressing weakly selecting TCRs whereas those that express stronger selecting TCRs are more effective at utilizing RasGRP1-independent mechanisms for ERK activation and positive selection. Analysis of RasGRP1−/− peripheral T cells also revealed hitherto unidentified functions of RasGRP1 in regulating T cell homeostasis and sustaining antigen-induced developmental programming

Stimulation of TLR4 by recombinant HSP70 requires structural integrity of the HSP70 protein itself

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor 4 (TLR4) is activated by bacterial endotoxin, a prototypical pathogen-associated molecular pattern (PAMP). It has been suggested that TLR4 can also be activated by damage-associated molecular pattern (DAMP) proteins such as HSP70. It remains a challenge to provide unequivocal evidence that DAMP proteins themselves play a role in TLR4 activation, as the DAMP proteins used are often contaminated with endotoxin and other TLR ligands introduced during protein expression and/or purification.</p> <p>Results</p> <p>Here we report that the activation of TLR4 on primary human macrophage cultures by recombinant HSP70 is not solely due to contaminating endotoxin. Polymyxin B pretreatment of HSP70 preparations to neutralize contaminating endotoxin caused significant reductions in the amount of TNF-α induced by the recombinant protein as determined by ELISA. However, digestion of HSP70 with Proteinase K-agarose beads also dramatically reduced the TNF-α response of macrophages to HSP70, while leaving levels of contaminating endotoxin largely unchanged relative to controls.</p> <p>Conclusions</p> <p>These results indicate that the stimulatory effect of recombinant HSP70 requires both the presence of endotoxin and structural integrity of the heat shock protein itself.</p

Familial Recurrence of Cerebral Palsy with Multiple Risk Factors

The recurrence of cerebral palsy in the same family is uncommon. We, however, report on two families with two or more affected siblings. In both families, numerous potential risk factors were identified including environmental, obstetric, and possible maternal effects. We hypothesize that multiple risk factors may lead to the increased risk of recurrence of cerebral palsy in families. Intrinsic and maternal risk factors should be investigated in all cases of cerebral palsy to properly counsel families on the risk of recurrence. Recent studies of genetic polymorphisms associated with cerebral palsy are considered with reference to our observations in these two families

Synthetic Compound Libraries Displayed on the Surface of Encoded Bacteriophage

AbstractWe describe a technology for attaching libraries of synthetic compounds to coat proteins of bacteriophage particles such that the identity of the chemical structure is encoded in the genome of the phage, analogous to peptides displayed on phage surfaces by conventional phage-display techniques. This format allows a library of synthetic compounds to be screened very efficiently as a single pool. Encoded phage serve as extremely robust reporters of the presence of each compound, providing exquisite sensitivity for identification of active compounds engaged in complex biological processes such as receptor-mediated endocytosis and transcytosis. To evaluate this approach, we constructed a library of 980 analogs of folic acid displayed on T7 phage, and demonstrated rapid identification of compounds that bind to folate receptor and direct endocytosis of associated phage particles into cells that express the targeted receptor

Global citizenship as the completion of cosmopolitanism

A conception of global citizenship should not be viewed as separate from, or synonymous with, the cosmopolitan moral orientation, but as a primary component of it. Global citizenship is fundamentally concerned with individual moral requirements in the global frame. Such requirements, framed here as belonging to the category of individual cosmopolitanism, offer guidelines on right action in the context of global human community. They are complementary to the principles of moral cosmopolitanism – those to be used in assessing the justice of global institutions and practices – that have been emphasised by cosmopolitan political theorists. Considering principles of individual and moral cosmopolitanism together can help to provide greater clarity concerning individual duties in the absence of fully global institutions, as well as clarity on individual obligations of justice in relation to emerging and still-developing trans-state institutions

Interleukin-1 regulates multiple atherogenic mechanisms in response to fat feeding

Background: Atherosclerosis is an inflammatory process that develops in individuals with known risk factors that include hypertension and hyperlipidaemia, influenced by diet. However, the interplay between diet, inflammatory mechanisms and vascular risk factors requires further research. We hypothesised that interleukin-1 (IL-1) signaling in the vessel wall would raise arterial blood pressure and promote atheroma. Methodology/Principal Findings: Apoe(-/-) and Apoe(-/-)/IL-1R1(-/-) mice were fed high fat diets for 8 weeks, and their blood pressure and atherosclerosis development measured. Apoe(-/-)/IL-R1(-/-) mice had a reduced blood pressure and significantly less atheroma than Apoe(-/-) mice. Selective loss of IL-1 signaling in the vessel wall by bone marrow transplantation also reduced plaque burden (p<0.05). This was associated with an IL-1 mediated loss of endothelium-dependent relaxation and an increase in vessel wall Nox 4. Inhibition of IL-1 restored endothelium-dependent vasodilatation and reduced levels of arterial oxidative stress. Conclusions/Significance: The IL-1 cytokine system links atherogenic environmental stimuli with arterial inflammation, oxidative stress, increased blood pressure and atherosclerosis. This is the first demonstration that inhibition of a single cytokine can block the rise in blood pressure in response to an environmental stimulus. IL-1 inhibition may have profound beneficial effects on atherogenesis in man

The ethical challenge of Touraine's 'living together'

In Can We Live Together? Alain Touraine combines a consummate analysis of crucial social tensions in contemporary societies with a strong normative appeal for a new emancipatory 'Subject' capable of overcoming the twin threats of atomisation or authoritarianism. He calls for a move from 'politics to ethics' and then from ethics back to politics to enable the new Subject to make a reality out of the goals of democracy and solidarity. However, he has little to say about the nature of such an ethics. This article argues that this lacuna could usefully be filled by adopting a form of radical humanism found in the work of Erich Fromm. It defies convention in the social sciences by operating from an explicit view of the 'is' and the 'ought' of common human nature, specifying reason, love and productive work as the qualities to be realised if we are to move closer to human solidarity. Although there remain significant philosophical and political differences between the two positions, particularly on the role to be played by 'the nation', their juxtaposition opens new lines of inquiry in the field of cosmopolitan ethics