The Distribution of plasma and other cells containing immunoglobin in the respiratory tract of normal man, and the alterations found in subjects with chronic bronchitis

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A pollen/dinoflagellate chronology for DSDP Site 480, Gulf of California

DSDP Site 480 in the Gulf of California represents a paleoclimatic record of great potential significance. Much of the 152-meter section is varved, which means that proxy records of climatic change can be analyzed with unusual precision on a variety of time scales. In this paper we present pollen and dinoflagellate evidence that suggests that the base of the section is much older than was previously thought. We propose a basal date of between 300,000 and 350,000 YBP

High-resolution natural recording systems: intercomparisons of the response to interannual climatic variability [abstract]

The goal of this work is to examine the properties of recording mechanisms which are common to continuously recording high-resolution natural systems in which climatic signals are imprinted and preserved as proxy records. These systems produce seasonal structures as an indirect response to climatic variability over the annual cycle. We compare the proxy records from four different high-resolution systems: the Quelccaya ice cap of the Peruvian Andes; composite tree ring growth from southern California and the southwestern United States; and the marine varve sedimentation systems in the Santa Barbara basin (off California, United States) and in the Gulf of California, Mexico. An important focus of this work is to indicate how the interannual climatic signal is recorded in a variety of different natural systems with vastly different recording mechanisms and widely separated in space. These high-resolution records are the products of natural processes which should be comparable, to some degree, to human-engineered systems developed to transmit and record physical quantities. We therefore present a simple analogy of a data recording system as a heuristic model to provide some unifying concepts with which we may better understand the formation of the records. This analogy assumes special significance when we consider that natural proxy records are the principal means to extend our knowledge of climatic variability into the past, beyond the limits of instrumentally recorded data

Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

Background<p></p> Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.<p></p> Methods<p></p> We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.<p></p> Results<p></p> Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.<p></p> Conclusions<p></p> We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis

Middle Neolithic pits and a burial at West Amesbury, Wiltshire

Excavations on the south-eastern slopes of King Barrow Ridge, 1.5 km east of Stonehenge, revealed five pits, a grave and other features of Middle Neolithic date. Analysis of the pit assemblages and the partial inhumation interred in the grave has provided insights into lifeways in this landscape in the late fourth millennium cal BC. Evidence suggests that the area was visited by a pastoralist, mobile community on a semi-regular basis for a significant period, in late autumn or winter. Selected remnants of craft-working and consumption were deposited in pits, before deliberate infilling. These depositions repeatedly memorialised activity on the hillside at a time of contemporary activity elsewhere on King Barrow Ridge and at the future site of Stonehenge. Middle Neolithic pits are present in significant numbers across King Barrow Ridge, and alongside pits in the Durrington area, form one of the densest concentrations of such activity in the region. Long distance mobility is suggested by the possible Irish origins of the inhumation, the first Middle Neolithic individual excavated in the environs of Stonehenge. Whilst of significance for understanding the Middle Neolithic in the WHS and the region, this research also hints at the roots of Late Neolithic monumentalisation of this landscape

Electrochromic cell with UV-curable electrolyte polymer for cohesion and strength

Electrically colourable (“electrochromic”) windows, hitherto confined to small areas, have recently been much expanded in area in new aircraft windows. Reviews indicate that to extend such high-tech applications to more everyday uses requires enhanced robustness, as in a new Prussian-Blue/polymer(Li+)/WO3 electrochromic device reported here. The new polymer electrolyte is UV-curable within the cell, obviating the need and risk of thermal polymerization while conferring mechanical robustness. Prussian Blue, (in reduced form the clear Prussian white “PW”, that is turned blue on electro-oxidation) and WO3 (showing a complementary clear-to-blue on electron uptake) are known to reliably undergo these established colourations as electrochromic anode and cathode, respectively

Application of the Wittig rearrangement of <i>N</i>-butyl-2-benzyloxybenzamides to synthesis of phthalide natural products and 3-aryl-3-benzyloxyisoindolinone anticancer agents

Application of the [1,2]-Wittig rearrangement and cyclisation approach to 3-arylphthalides has been evaluated for the synthesis of three bioactive natural products. While this is successful in the case of crycolide, providing the second synthesis of this compound, the more sterically demanding targets isopestacin and cryphonectric acid prove not to be amenable to this approach, with the 2,6-disubstituted aryl groups causing the failure of the rearrangement and alkylation steps, respectively. Direct oxidation of the substituted benzhydrols resulting from [1,2]-Wittig rearrangement using MnO2 provides a new route to 3-aryl-3-hydroxyisoindolinones, and this method has been used in the synthesis of two 3-aryl-3-benzyloxyisoindolinone anticancer agents