Imaging of Neurotransmitters and Small Molecules in Brain Tissues Using Laser Desorption/Ionization Mass Spectrometry Assisted with Zinc Oxide Nanoparticles.

Inorganic nanostructured materials such as silicon, carbon, metals, and metal oxides have been explored as matrices of low-background signals to assist the laser desorption/ionization (LDI) mass spectrometric (MS) analysis of small molecules, but their applications for imaging of small molecules in biological tissues remain limited in the literature. Titanium dioxide is one of the known nanoparticles (NP) that can effectively assist LDI MS imaging of low molecular weight molecules (LMWM). TiO2 NP is commercially available as dispersions, which can be applied using a chemical solution sprayer. However, aggregation of NP can occur in the dispersions and the aggregated NP can slowly clog the sprayer nozzle. In this work, the use of zinc oxide (ZnO) NP for LDI MS imaging is investigated as a superior alternative due to its dissolution in acidic pH. ZnO NP was found to deliver similar or better results in the imaging of LMWM in comparison to TiO2 NP. The regular acid washes were effective in minimizing clogging and maintaining high reproducibility. High-quality images of mouse sagittal and rat coronal tissue sections were obtained. Ions were detected predominately as Na+ or K+ adducts in the positive ion mode. The number of LMWM detected with ZnO NP was similar to that obtained with TiO2 NP, and only a small degree of specificity was observed

Human-ecodynamics and the intertidal zones of the Zanzibar Archipelago

The intertidal zone, covering the nearshore fringe of coasts and islands and extending from the high-water mark to areas that remain fully submerged, encompasses a range of habitats containing resources that are as important to modern populations as they were to humans in prehistory. Effectively bridging land and sea, intertidal environments are extremely dynamic, requiring complexity and variability in how people engaged with them in the past, much as they do in the present. Here we review and reconsider environmental, archaeological, and modern socio-ecological evidence from the Zanzibar Archipelago on eastern Africa’s Swahili coast, focusing on marine molluscs to gain insight into the trajectories of human engagement with nearshore habitats and resources. We highlight the potential drivers of change and/or stability in human-intertidal interactions through time and space, set against a backdrop of the significant socio-economic and socio-ecological changes apparent in the archipelago, and along the Swahili coast, during the late Holocene.1 Introduction 2 Background 2.1 Unguja and Pemba Islands, Zanzibar Archipelago 2.2 Archaeological and historical overview 2.3 Study site locations, descriptions and chronology 2.3.1 Northern Pemba: Pango la Watoro and Msuka Mjini 2.3.2 Southern Pemba: Ras Mkumbuu 2.3.3 Northern Unguja: Fukuchani and Mvuleni 2.3.4 Southern Unguja: Unguja Ukuu, Kuumbi Cave and Mifupani 2.4 Palaeoenvironmental context 3 Materials and methods 3.1 Identification and abundance 3.2 Richness, nestedness and taxonomic composition 3.3 Diversity indices 3.4 Molluscan zonation and benthic habitat attribution 4 Results 4.1 Assemblage characteristics 4.2 Richness and nestedness 4.3 Taxonomic composition 4.4 Assemblage diversity 4.5 Zonation and benthic habitat analysis 5 Discussion 6 Conclusio

Windsurfing : an extreme form of material and embodied interaction?

This paper makes reference to the development of water based board sports in the world of adventure or action games. With a specific focus on windsurfing, we use Parlebas (1999) and Warnier's (2001) theoretical interests in the praxaeology of physical learning as well as Mauss' (1935) work on techniques of the body. We also consider the implications of Csikzentimihalyi's notion of flow (1975). We argue that windsurfing equipment should not merely be seen as protection but rather as status objects through which extreme lifestyles are embodied and embodying

Δ9-tetrahydrocannabinol exposure during rat pregnancy leads to symmetrical fetal growth restriction and labyrinth-specific vascular defects in the placenta.

1 in 5 women report cannabis use during pregnancy, with nausea cited as their primary motivation. Studies show that (-)-△9-tetrahydrocannabinol (Δ9-THC), the major psychoactive ingredient in cannabis, causes fetal growth restriction, though the mechanisms are not well understood. Given the critical role of the placenta to transfer oxygen and nutrients from mother, to the fetus, any compromise in the development of fetal-placental circulation significantly affects maternal-fetal exchange and thereby, fetal growth. The goal of this study was to examine, in rats, the impact of maternal Δ9-THC exposure on fetal development, neonatal outcomes, and placental development. Dams received a daily intraperitoneal injection (i.p.) of vehicle control or Δ9-THC (3 mg/kg) from embryonic (E)6.5 through 22. Dams were allowed to deliver normally to measure pregnancy and neonatal outcomes, with a subset sacrificed at E19.5 for placenta assessment via immunohistochemistry and qPCR. Gestational Δ9-THC exposure resulted in pups born with symmetrical fetal growth restriction, with catch up growth by post-natal day (PND)21. During pregnancy there were no changes to maternal food intake, maternal weight gain, litter size, or gestational length. E19.5 placentas from Δ9-THC-exposed pregnancies exhibited a phenotype characterized by increased labyrinth area, reduced Epcam expression (marker of labyrinth trophoblast progenitors), altered maternal blood space, decreased fetal capillary area and an increased recruitment of pericytes with greater collagen deposition, when compared to vehicle controls. Further, at E19.5 labyrinth trophoblast had reduced glucose transporter 1 (GLUT1) and glucocorticoid receptor (GR) expression in response to Δ9-THC exposure. In conclusion, maternal exposure to Δ9-THC effectively compromised fetal growth, which may be a result of the adversely affected labyrinth zone development. These findings implicate GLUT1 as a Δ9-THC target and provide a potential mechanism for the fetal growth restriction observed in women who use cannabis during pregnancy

Precision Measurement of the Weak Mixing Angle in Moller Scattering

We report on a precision measurement of the parity-violating asymmetry in fixed target electron-electron (Moller) scattering: A_PV = -131 +/- 14 (stat.) +/- 10 (syst.) parts per billion, leading to the determination of the weak mixing angle \sin^2\theta_W^eff = 0.2397 +/- 0.0010 (stat.) +/- 0.0008 (syst.), evaluated at Q^2 = 0.026 GeV^2. Combining this result with the measurements of \sin^2\theta_W^eff at the Z^0 pole, the running of the weak mixing angle is observed with over 6 sigma significance. The measurement sets constraints on new physics effects at the TeV scale.Comment: 4 pages, 2 postscript figues, submitted to Physical Review Letter

Curvature fluctuations and Lyapunov exponent at Melting

We calculate the maximal Lyapunov exponent in constant-energy molecular dynamics simulations at the melting transition for finite clusters of 6 to 13 particles (model rare-gas and metallic systems) as well as for bulk rare-gas solid. For clusters, the Lyapunov exponent generally varies linearly with the total energy, but the slope changes sharply at the melting transition. In the bulk system, melting corresponds to a jump in the Lyapunov exponent, and this corresponds to a singularity in the variance of the curvature of the potential energy surface. In these systems there are two mechanisms of chaos -- local instability and parametric instability. We calculate the contribution of the parametric instability towards the chaoticity of these systems using a recently proposed formalism. The contribution of parametric instability is a continuous function of energy in small clusters but not in the bulk where the melting corresponds to a decrease in this quantity. This implies that the melting in small clusters does not lead to enhanced local instability.Comment: Revtex with 7 PS figures. To appear in Phys Rev

Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study

BACKGROUND: Asthma is a biologically heterogeneous disease and development of novel therapeutics requires understanding of pathophysiologic phenotypes. There is uncertainty regarding the stability of clinical characteristics and biomarkers in asthma over time. This report presents the longitudinal stability over 12 months of clinical characteristics and clinically accessible biomarkers from ADEPT. METHODS: Mild, moderate, and severe asthma subjects were assessed at 5 visits over 12 months. Assessments included patient questionnaires, spirometry, bronchodilator reversibility, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum. RESULTS: Mild (n = 52), moderate (n = 55), and severe (n = 51) asthma cohorts were enrolled from North America and Western Europe. For all clinical characteristics and biomarkers, group mean data showed no significant change from visit to visit. However, individual data showed considerable variability. FEV1/FVC ratio showed excellent reproducibility while pre-bronchodilator FEV1 and FVC were only moderately reproducible. Of note bronchodilator FEV1 reversibility showed low reproducibility, with the nonreversible phenotype much more reproducible than the reversible phenotype. The 7-item asthma control questionnaire (ACQ7) demonstrated moderate reproducibility for the combined asthma cohorts, but the uncontrolled asthma phenotype (ACQ7 > 1.5) was inconstant in mild and moderate asthma but stable in severe asthma. FENO demonstrated good reproducibility, with the FENO-low phenotype (FENO < 35 ppb) more stable than the FENO-high phenotype (FENO ≥ 35 ppb). Induced sputum inflammatory phenotypes showed marked variability across the 3 sputum samples taken over 6 months. CONCLUSIONS: The ADEPT cohort showed group stability, individual stability in some parameters e.g. low FEV1/FVC ratio, and low FENO, but marked individual variability in other clinical characteristics and biomarkers e.g. type-2 biomarkers over 12 months. This variability is possibly related to seasonal variations in climate and allergen exposure, medication changes and acute exacerbations. The implications for patient selection strategies based on clinical biomarkers may be considerable

Defect-unbinding transitions and inherent structures in two dimensions

We present a large-scale (36000-particle) computational study of the "inherent structures" (IS) associated with equilibrium, two-dimensional, one-component Lennard-Jones systems. Our results provide strong support both for the inherent-structures theory of classical fluids, and for the KTHNY theory of two-stage melting in two dimensions. This support comes from the observation of three qualitatively distinct "phases" of inherent structures: a crystal, a "hexatic glass", and a "liquid glass". We also directly observe, in the IS, analogs of the two defect-unbinding transitions (respectively, of dislocations, and disclinations) believed to mediate the two equilibrium phase transitions. Each transition shows up in the inherent structures---although the free disclinations in the "liquid glass" are embedded in a percolating network of grain boundaries. The bond-orientational correlation functions of the inherent structures show the same progressive loss of order as do the three equilibrium phases: long-range to quasi-long-range to short-range.Comment: RevTeX, 8 pages, 15 figure