From alpha-cedrene to crinipellin B and onward: 25 years of the alkene-arene meta-photocycloaddition reaction in natural product synthesis

Wender and Howbert's remarkable synthesis of alpha-cedrene in 1981 brought the attention of the synthetic community to the alkene - arene meta-photocycloaddition reaction. Here we review the natural product syntheses that have been achieved, over the last 25 years, utilising this strategic level reaction.

Relation between the fatty acid composition of peripheral blood mononuclear cells and measures of immune cell function in health free-living subjects aged 25-72 y

Background: There is little information about the relation between the fatty acid composition of human immune cells and the function of those cells over the habitual range of fatty acid intakes. Objective: The objective of the study was to determine the relation between the fatty acid composition of human peripheral blood mononuclear cell (PBMC) phospholipids and the functions of human immune cells. Design: One hundred fifty healthy adult subjects provided a fasting blood sample. The phagocytic and oxidative burst activities of monocytes and neutrophils were measured in whole blood. PBMCs were isolated and used to measure lymphocyte proliferation in response to the T cell mitogen concanavalin A and the production of cytokines in response to concanavalin A or bacterial lipopolysaccharide. The fatty acid composition of plasma and PBMC phospholipids was determined. Results: Wide variations in fatty acid composition of PBMC phospholipids and immune cell functions were identified among the subjects. The proportions of total Polyunsaturated fatty acids (PUFAs), of total n-6 and n-3 PUFAs, and of several individual PUFAs in PBMC phospholipids were positively correlated with phagocytosis by neutrophils and monocytes, neutrophil oxidative burst, lymphocyte proliferation, and interferon gamma production. The ratios of saturated fatty acids to PUFAs and of n-6 to n-3 PUFAs were negatively correlated with these same immune functions. The relation of PBMC fatty acid composition to monocyte oxidative burst was the reverse of its relation to monocyte phagocytosis and neutrophil oxidative burst. Conclusion: Variations in the fatty acid composition of PBMC phospholipids account for some of the variability in immune cell functions among healthy adults.

A comparison of extra-tropical cyclones in recent re-analyses; ERA-Interim, NASA MERRA, NCEP CFSR and JRA-25

Extra-tropical cyclones are identified and compared using data from four recent re-analyses for the winter periods in both hemispheres. Results show the largest differences occur between the older lower resolution JRA25 re-analysis when compared with the newer high resolution re-analyses, in particular in the Southern Hemisphere (SH). Spatial differences between the newest re-analyses are small in both hemispheres and generally not significant except some common regions associated with cyclogenesis close to orography. Intensities are generally related to spatial resolution except NASA-MERRA which has larger intensities for several different measures. Matching storms between re-analyses shows the number matched between ERA-Interim and the other re-analyses are similar in the Northern Hemisphere (NH). In the SH the number matched between JRA25 and ERA-Interim is lower than in the NH, but for NASA-MERRA and NCEP-CFSR the number matched is similar to the NH. The mean separation of the identically same cyclones is typically less than 20 geodesic in both hemispheres for the latest re-analyses, whereas JRA25 compared with the other re-analyses has a broader distribution in the SH indicating greater uncertainty. The instantaneous intensity differences for matched storms shows narrow distributions for pressure while for winds and vorticity the distributions are much broader indicating larger uncertainty typical of smaller scale fields. Composite cyclone diagnostics show that cyclones are very similar between the re-analyses, with differences being related to the intensities, consistent with the intensity results. Overall, results show NH cyclones correspond well between re-analyses, with a significant improvement in the SH for the latest re-analyses, indicating a convergence between re-analyses for cyclone properties.

A policy critique of Stansted Airport's expansion to 25 million passengers per annum (MPPA)

In this paper we undertake a preliminary assessment of the regional planning and development implications of BAA Stansted Airport’s planning permission to grow to 25 million passengers per annum (mppa) by 2010. Our concern is not simply to consider the overall growth of the airport on the airport site itself but the nature and type of growth both on- and off-site. In this document we focus on the submitted planning permission documents and test them. The methodology we employed was to draw on published and unpublished numerical estimates of the airport’s growth – particularly including estimates produced by the airport owner, BAA, and their economic and planning consultants DTZ Pieda - and critically, and systematically analyse their figures. We adopted this approach because unless the figures which were employed in the initial calculations were correct then all of the subsequent projections which flow from them - and the polices which could then be based on them – could be flawed. The analysis is divided into two parts – firstly, are the growth forecasts correct?; and secondly, what do these forecasts actually mean in developmental terms? In effect, what we have done is to produce a critique of the existing body of evidence by questioning underpinning assumptions and then draw some preliminary conclusions for the region based on this analysis. A major focus of this report has been analyse the figures involved in the planning application to expand Stansted to 25mppa. Ironically, one of our key findings, that the local impact of Stansted’s proposed expansion in employment terms might well be less than was originally thought, might make it easier to gain the acceptance of the relevant local authorities involved to allow the development to take place. Our main overall findings are that the BAA projections over-estimate the local employment impact of the airport’s proposed growth and under-estimate its potential regional ‘transportation’ employment effect. These two findings are, of course, related to each other in important ways, and we also feel that they have potentially significant medium and long-term economic, competitiveness and planning policy implications for the East of England region

APOA5 genotype influences the association between 25-hydroxyvitamin D and high density lipoprotein cholesterol

OBJECTIVE: Circulating levels of 25-hydroxyvitamin D (25OHD) are positively associated with high density lipoprotein (HDL) cholesterol. We sought to replicate a previously reported interaction between APOA5 genotype and vitamin D, and to examine whether HDL-associated genetic loci modify the association between serum 25OHD and HDL cholesterol. METHODS: We examined whether 42 single nucleotide polymorphisms (SNPs) modify the association between serum 25OHD and HDL cholesterol in the 1958 British Birth cohort (aged 45 years, n = 4978). RESULTS: We identified a borderline interaction between the SNP rs12272004 (near the APOA5) and serum 25OHD on HDL cholesterol (P(interaction) = 0.05). The interaction was particularly prominent among the samples collected during winter (P(interaction) = 0.001). None of the other loci showed an interaction with serum 25OHD concentrations on HDL cholesterol. CONCLUSIONS: Our study in 4978 British Whites provides further support that APOA5 genotype modifies the association between vitamin D metabolites and HDL cholesterol.

Measurements of stratospheric ozone at a mid-latitude observing station Valentia, Ireland (51.94° N, 10.25° W), using ground-based and ozonesonde observations from 1994 to 2009

Sixteen years (1994 – 2009) of ozone profiling by ozonesondes at Valentia Meteorological and Geophysical Observatory, Ireland (51.94° N, 10.23° W) along with a co-located MkIV Brewer spectrophotometer for the period 1993–2009 are analyzed. Simple and multiple linear regression methods are used to infer the recent trend, if any, in stratospheric column ozone over the station. The decadal trend from 1994 to 2010 is also calculated from the monthly mean data of Brewer and column ozone data derived from satellite observations. Both of these show a 1.5 % increase per decade during this period with an uncertainty of about ±0.25 %. Monthly mean data for March show a much stronger trend of ~ 4.8 % increase per decade for both ozonesonde and Brewer data. The ozone profile is divided between three vertical slots of 0–15 km, 15–26 km, and 26 km to the top of the atmosphere and a 11-year running average is calculated. Ozone values for the month of March only are observed to increase at each level with a maximum change of +9.2 ± 3.2 % per decade (between years 1994 and 2009) being observed in the vertical region from 15 to 26 km. In the tropospheric region from 0 to 15 km, the trend is positive but with a poor statistical significance. However, for the top level of above 26 km the trend is significantly positive at about 4 % per decade. The March integrated ozonesonde column ozone during this period is found to increase at a rate of ~6.6 % per decade compared with the Brewer and satellite positive trends of ~5 % per decade.

Interaction between vitamin D receptor gene polymorphisms and 25-hydroxyvitamin D concentrations on metabolic and cardiovascular disease outcomes

AIM: 25-hydroxyvitamin D (25OHD) concentrations have been shown to be associated with major clinical outcomes, with a suggestion that individual risk may vary according to common genetic differences in the vitamin D receptor (VDR) gene. Hence, we tested for the interactions between two previously studied VDR polymorphisms and 25OHD on metabolic and cardiovascular disease-related outcomes in a large population-based study. METHODS: Interactions between two previously studied VDR polymorphisms (rs7968585 and rs2239179) and 25OHD concentrations on metabolic and cardiovascular disease-related outcomes such as obesity- (body mass index, waist circumference, waist-hip ratio (WHR)), cardiovascular- (systolic and diastolic blood pressure), lipid- (high- and low-density lipoprotein, triglycerides, total cholesterol), inflammatory- (C-reactive protein, fibrinogen, insulin growth factor-1, tissue plasminogen activator) and diabetes- (glycated haemoglobin) related markers were examined in the 1958 British Birth cohort (n up to 5160). Interactions between each SNP and 25OHD concentrations were assessed using linear regression and the likelihood ratio test. RESULTS: After Bonferroni correction, none of the interactions reached statistical significance except for the interaction between the VDR SNP rs2239179 and 25OHD concentrations on waist-hip ratio (WHR) (P=0.03). For every 1nmol/L higher 25OHD concentrations, the association with WHR was stronger among those with two major alleles (-4.0%, P=6.26e-24) compared to those with either one or no major alleles (-2.3%, P≤8.201e-07, for both) of the VDR SNP rs2239179. CONCLUSION: We found no evidence for VDR polymorphisms acting as major modifiers of the association between 25OHD concentrations and cardio-metabolic risk. Interaction between VDR SNP rs2239179 and 25OHD on WHR warrants further confirmation.

Response to comment on “The response of vegetation on the Andean flank in western Amazonia to Pleistocene climate change” – M.L. Cárdenas et al., Science 331, 1055 (25 February 2011)”.

Puyasena et al. question our interpretation of climate-driven vegetation change on the Andean flank in western Amazonia during the middle Pleistocene and suggest that the use of Podocarpus spp. as a proxy of past climate change should be reassessed. We defend our assertion that vegetation change at the Erazo study site was predominantly driven by climate change due to concomitant changes recorded by multiple taxa in the fossil record.

Hydrology and climatology at Laguna La Gaiba, lowland Bolivia: complex responses to climatic forcings over the last 25,000 years

Diatom, geochemical and isotopic data provide a record of environmental change in Laguna La Gaiba, lowland Bolivia (17°450S, 57°350W), over the last ca. 25 000 years. High-resolution diatom analysis around the Last Glacial–Interglacial Transition provides new insights into this period of change. The full and late glacial lake was generally quite shallow, but with evidence of periodic flooding. At about 13 100 cal a BP, just before the start of the Younger Dryas chronozone, the diatoms indicate shallower water conditions, but there is a marked change at about 12 200 cal a BP indicating the onset of a period of high variability, with rising water levels punctuated by periodic drying. From ca. 11 800 to 10 000 cal a BP, stable, deeper water conditions persisted. There is evidence for drying in the early to middle Holocene, but not as pronounced as that reported from elsewhere in the southern hemisphere tropics of South America. This was followed by the onset of wetter conditions in the late Holocene consistent with insolation forcing. Conditions very similar to present were established about 2100 cal a BP. A complex response to both insolation forcing and millennial-scale events originating in the North Atlantic is noted.

Effective interventions: 25 years outside the mainstream

25 years ago when the Durham conferences were in full swing, I presented results of investigations on language and behaviour in autism. I tentatively proposed that early language in autism might tell us about the cognitive skills of people with ASD and the behaviour might lead to greater understanding of which brain systems might be affected. In this presentation, I will update these topics and present a summary of other work I have been involved with in attempting to improve the lives of people with autism and their families. Data on three people with autism at the early stages of speech development showed an unusual pattern of learning colour and number names early. One possibility was that this skill represented a sign of weak central coherence – they only attended to one dimension. Colleagues of mine were equally puzzled so we tried to find out if my results could be replicated – they were not (see Schafer, Williams & Smith, 2014). Instead we found this pattern was also seen in Down Syndrome, but that early vocabulary in autism was associated with low Colorado Meaningfulness at least in comprehension. The Colorado Meaningfulness of a word is a measure of how many words can be associated with it and often involve extensive use of context. Our data suggest that the number of contexts in which a particular word can appear has a role in determining vocabulary in ASD which is consistent with the weak central coherence theory of autism. In the course of this work I also came across a group of young people with autism who appeared to have a written vocabulary but not a spoken one. It seems possible that print might be a medium of communication when speech is not. Repetitive behaviour in autism remains a mystery. We can use functional analysis to determine why the behaviour occurs, but a worryingly large percentage of behaviours are described as being internally driven or sensory reinforced. What does that mean in terms of brain activity – could it be system analogous to epilepsy, where brain activity becomes inappropriately synchronised? At the moment I cannot claim to have solved this problem, but if sensation is a driver then sensory interventions should make a difference. Data from a recent study will be presented to suggest that for some individuals this is the case. Social behaviour remains the key however, and it remains to be seen whether it is possible for social behaviour to be aided. One route that has potential is direct teaching of skills through drama and working with others who do not have social difficulties of the same type. The picture is complicated by changes in social skills with age and experience, but the failure of people with ASD to interact when in settings of social contact is little researched.

The Cold War in retrospect : 25 years after its end

This special issue of Cold War History offers a retrospective on the end of the Cold War, 25 years after its peaceful conclusion. This peaceful conclusion is an achievement that cannot be celebrated enough, and we must continue to build international relations in conflict and co-operation on this awareness of our common humanity and our common human fallibility.

Orbital and millenial-scale environmental changes between 64 and 25 ka BP recorded in Black Sea sediments

High-resolution pollen and dinoflagellate cyst records from sediment core M72/5-25-GC1 were used to reconstruct vegetation dynamics in northern Anatolia and surface conditions of the Black Sea between 64 and 20 ka BP. During this period, the dominance of Artemisia in the pollen record indicates a steppe landscape and arid climate conditions. However, the concomitant presence of temperate arboreal pollen suggests the existence of glacial refugia in northern Anatolia. Long-term glacial vegetation dynamics reveal two major arid phases ~64–55 and 40–32 ka BP, and two major humid phases ~54–45 and 28–20 ka BP, correlating with higher and lower summer insolation, respectively. Dansgaard–Oeschger (D–O) cycles are clearly indicated by the 25-GC1 pollen record. Greenland interstadials are characterized by a marked increase in temperate tree pollen, indicating a spread of forests due to warm/wet conditions in northern Anatolia, whereas Greenland stadials reveal cold and arid conditions as indicated by spread of xerophytic biomes. There is evidence for a phase lag of ~500 to 1500 yr between initial warming and forest expansion, possibly due to successive changes in atmospheric circulation in the North Atlantic sector. The dominance of Pyxidinopsis psilata and Spiniferites cruciformis in the dinocyst record indicates brackish Black Sea conditions during the entire glacial period. The decrease of marine indicators (marine dinocysts, acritarchs) at ~54 ka BP and increase of freshwater algae (Pediastrum, Botryococcus) from 32 to 25 ka BP reveals freshening of the Black Sea surface water. This freshening is possibly related to humid phases in the region, to connection between Caspian Sea and Black Sea, to seasonal freshening by floating ice, and/or to closer position of river mouths due to low sea level. In the southern Black Sea, Greenland interstadials are clearly indicated by high dinocyst concentrations and calcium carbonate content, as a result of an increase in primary productivity. Heinrich events show a similar impact on the environment in the northern Anatolia/Black Sea region as Greenland stadials.