Hippocampal capillary pericytes in post-stroke and vascular dementias and Alzheimer’s disease and experimental chronic cerebral hypoperfusion

\ua9 The Author(s) 2024. Neurovascular unit mural cells called ‘pericytes’ maintain the blood-brain barrier and local cerebral blood flow. Pathological changes in the hippocampus predispose to cognitive impairment and dementia. The role of hippocampal pericytes in dementia is largely unknown. We investigated hippocampal pericytes in 90 post-mortem brains from post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer’s disease (AD), and AD-VaD (Mixed) subjects, and post-stroke non-demented survivors as well as similar age controls. We used collagen IV immunohistochemistry to determine pericyte densities and a mouse model of VaD to validate the effects of chronic cerebral hypoperfusion. Despite increased trends in hippocampal microvascular densities across all dementias, mean pericyte densities were reduced by ~25–40% in PSD, VaD and AD subjects compared to those in controls, which calculated to 14.1 \ub1 0.7 per mm capillary length, specifically in the cornu ammonis (CA) 1 region (P = 0.01). In mice with chronic bilateral carotid artery occlusion, hippocampal pericyte loss was ~60% relative to controls (P < 0.001). Pericyte densities were correlated with CA1 volumes (r = 0.54, P = 0.006) but not in any other sub-region. However, mice subjected to the full-time environmental enrichment (EE) paradigm showed remarkable attenuation of hippocampal CA1 pericyte loss in tandem with CA1 atrophy. Our results suggest loss of hippocampal microvascular pericytes across common dementias is explained by a vascular aetiology, whilst the EE paradigm offers significant protection

Comparison of aromatic hydrocarbon measurements made by PTR-MS, DOAS and GC-FID during the MCMA 2003 Field Experiment

A comparison of aromatic hydrocarbon measurements is reported for the CENICA supersite in the district of Iztapalapa during the Mexico City Metropolitan Area field experiment in April 2003 (MCMA 2003). Data from three different measurement methods were compared: a Proton Transfer Reaction Mass Spectrometer (PTR-MS), long path measurements using a UV Differential Optical Absorption Spectrometer (DOAS), and Gas Chromatography-Flame Ionization analysis (GC-FID) of canister samples. The principle focus was on the comparison between PTR-MS and DOAS data. Lab tests established that the PTR-MS and DOAS calibrations were consistent for a suite of aromatic compounds including benzene, toluene, p-xylene, ethylbenzene, 1,2,4-trimethylbenzene, phenol and styrene. The point sampling measurements by the PTR-MS and GC-FID showed good correlations (r=0.6), and were in reasonable agreement for toluene, C2-alkylbenzenes and C3-alkylbenzenes. The PTR-MS benzene data were consistently high, indicating interference from ethylbenzene fragmentation for the 145 Td drift field intensity used in the experiment. Correlations between the open-path data measured at 16-m height over a 860-m path length (retroreflector in 430 m distance), and the point measurements collected at 37-m sampling height were best for benzene (r=0.61), and reasonably good for toluene, C2-alkylbenzenes, naphthalene, styrene, cresols and phenol (r>0.5). There was good agreement between DOAS and PTR-MS measurements of benzene after correction for the PTR-MS ethylbenzene interference. Mixing ratios measured by DOAS were on average a factor of 1.7 times greater than the PTR-MS data for toluene, C2-alkylbenzenes, naphthalene and styrene. The level of agreement for the toluene data displayed a modest dependence on wind direction, establishing that spatial gradients – horizontal, vertical, or both – in toluene mixing ratios were significant, and up to a factor of 2 despite the fact that all measurements were conducted above roof level. Our analysis highlights a potential problem in defining a VOC sampling strategy that is meaningful for the comparison with photochemical transport models: meaningful measurements require a spatial fetch that is comparable to the grid cell size of models, which is typically a few 10 km2. Long-path DOAS measurements inherently average over a larger spatial scale than point measurements. The spatial representativeness can be further increased if observations are conducted outside the surface roughness sublayer, which might require measurements at altitudes as high as 10 s of metres above roof level.Alexander von Humboldt-Stiftung (Feodor Lynen fellowship)Henry & Camille Dreyfus Foundation (Postdoctral Fellowship in Environmental Chemistry

Establishing Lagrangian connections between observations within air masses crossing the Atlantic during the International Consortium for Atmospheric Research on Transport and Transformation experiment

The ITCT-Lagrangian-2K4 (Intercontinental Transport and Chemical Transformation) experiment was conceived with an aim to quantify the effects of photochemistry and mixing on the transformation of air masses in the free troposphere away from emissions. To this end, attempts were made to intercept and sample air masses several times during their journey across the North Atlantic using four aircraft based in New Hampshire (USA), Faial (Azores) and Creil (France). This article begins by describing forecasts from two Lagrangian models that were used to direct the aircraft into target air masses. A novel technique then identifies Lagrangian matches between flight segments. Two independent searches are conducted: for Lagrangian model matches and for pairs of whole air samples with matching hydrocarbon fingerprints. The information is filtered further by searching for matching hydrocarbon samples that are linked by matching trajectories. The quality of these "coincident matches'' is assessed using temperature, humidity and tracer observations. The technique pulls out five clear Lagrangian cases covering a variety of situations and these are examined in detail. The matching trajectories and hydrocarbon fingerprints are shown, and the downwind minus upwind differences in tracers are discussed

Regularizing Portfolio Optimization

The optimization of large portfolios displays an inherent instability to estimation error. This poses a fundamental problem, because solutions that are not stable under sample fluctuations may look optimal for a given sample, but are, in effect, very far from optimal with respect to the average risk. In this paper, we approach the problem from the point of view of statistical learning theory. The occurrence of the instability is intimately related to over-fitting which can be avoided using known regularization methods. We show how regularized portfolio optimization with the expected shortfall as a risk measure is related to support vector regression. The budget constraint dictates a modification. We present the resulting optimization problem and discuss the solution. The L2 norm of the weight vector is used as a regularizer, which corresponds to a diversification "pressure". This means that diversification, besides counteracting downward fluctuations in some assets by upward fluctuations in others, is also crucial because it improves the stability of the solution. The approach we provide here allows for the simultaneous treatment of optimization and diversification in one framework that enables the investor to trade-off between the two, depending on the size of the available data set

‘The longest suicide vote in history’: the Labour Party leadership election of 2015

The Labour leadership contest of 2015 resulted in the election of the veteran Left-wing backbencher, Jeremy Corbyn, who clearly defeated the early favourite, Andy Burnham. Yet Corbyn enjoyed very little support among Labour MPs, and his victory plunged the PLP into turmoil, particularly as he was widely viewed as incapable of leading the Party to victory in the 2020 general election. Given that, much of the established academic literature on Party leadership contests emphasises the ability to foster unity, and thereby render a party electable, as two of the key criteria for electing a new leader, coupled with overall competence, important questions are raised about how and why the Labour Party chose someone to lead them who clearly does not meet these criteria. We will argue that whilst these are the natural priorities of MPs when electing a new leader, in Corbyn’s case, much of the extra-parliamentary Labour Party was more concerned about ideological conviction and purity of principles, regardless of how far these diverged from public opinion. This was especially true of those who signed-up to the Labour Party following the 2015 general election defeat. Indeed, many of these only did so after Corbyn had become a candidate. This clearly suggests a serious tension between maximising intra-party democracy and ensuring the electability of the parliamentary party itself

Genome Profiling (GP) Method Based Classification of Insects: Congruence with That of Classical Phenotype-Based One

Ribosomal RNAs have been widely used for identification and classification of species, and have produced data giving new insights into phylogenetic relationships. Recently, multilocus genotyping and even whole genome sequencing-based technologies have been adopted in ambitious comparative biology studies. However, such technologies are still far from routine-use in species classification studies due to their high costs in terms of labor, equipment and consumables.Here, we describe a simple and powerful approach for species classification called genome profiling (GP). The GP method composed of random PCR, temperature gradient gel electrophoresis (TGGE) and computer-aided gel image processing is highly informative and less laborious. For demonstration, we classified 26 species of insects using GP and 18S rDNA-sequencing approaches. The GP method was found to give a better correspondence to the classical phenotype-based approach than did 18S rDNA sequencing employing a congruence value. To our surprise, use of a single probe in GP was sufficient to identify the relationships between the insect species, making this approach more straightforward.The data gathered here, together with those of previous studies show that GP is a simple and powerful method that can be applied for actually universally identifying and classifying species. The current success supported our previous proposal that GP-based web database can be constructible and effective for the global identification/classification of species

Choosing party leaders: Anglophone democracies, British parties and the limits of comparative politics

Since 1965, Britain’s major political parties have radically, and repeatedly, changed the ways in which they choose their leaders. Building on a recent comparative study of party leadership selection in the five principal Anglophone (‘Westminster’) parliamentary democracies (Cross and Blais, 2012a), this article first outlines a theoretical framework that purports to explain why the major parties in three of those countries, including Britain, have adopted such reform. It then examines why five major British parties have done so since 1965. It argues that, while Cross and Blais’ study makes a significant contribution to our knowledge and understanding of processes of party leadership selection reform in Anglophone parliamentary democracies, it has limited explanatory power when applied to changes enacted by the major parties in modern and contemporary Britain. Instead, the adoption of such reform in the British context is ultimately best understood and explained by examining both the internal politics and external circumstances of individual parties

Female germ unit in Genlisea and Utricularia, with remarks about the evolution of the extra-ovular female gametophyte in members of Lentibulariaceae

Lentibulariaceae is the largest family among carnivorous plants which displays not only an unusual morphology and anatomy but also the special evolution of its embryological characteristics. It has previously been reported by authors that Utricularia species lack a filiform apparatus in the synergids. The main purposes of this study were to determine whether a filiform apparatus occurs in the synergids of Utricularia and its sister genus Genlisea, and to compare the female germ unit in these genera. The present studies clearly show that synergids in both genera possess a filiform apparatus; however, it seems that Utricularia quelchii synergids have a simpler structure compared to Genlisea aurea and other typical angiosperms. The synergids are located at the terminal position in the embryo sacs of Pinguicula, Genlisea and were probably also located in that position in common Utricularia ancestor. This ancestral characteristic still occurs in some species from the Bivalvaria subgenus. An embryo sac, which grows out beyond the limit of the integument and has contact with nutritive tissue, appeared independently in different Utricularia lineages and as a consequence of this, the egg apparatus changes position from apical to lateral