First Passage Time in a Two-Layer System

As a first step in the first passage problem for passive tracer in stratified porous media, we consider the case of a two-dimensional system consisting of two layers with different convection velocities. Using a lattice generating function formalism and a variety of analytic and numerical techniques, we calculate the asymptotic behavior of the first passage time probability distribution. We show analytically that the asymptotic distribution is a simple exponential in time for any choice of the velocities. The decay constant is given in terms of the largest eigenvalue of an operator related to a half-space Green's function. For the anti-symmetric case of opposite velocities in the layers, we show that the decay constant for system length $L$ crosses over from $L^{-2}$ behavior in diffusive limit to $L^{-1}$ behavior in the convective regime, where the crossover length $L^*$ is given in terms of the velocities. We also have formulated a general self-consistency relation, from which we have developed a recursive approach which is useful for studying the short time behavior.Comment: LaTeX, 28 pages, 7 figures not include

C-axis Penetration Depth and Inter-layer Conductivity in the Thallium Based Cuprate Superconductors

The c-axis Josephson plasmon in optimally doped single-layer and bi-layer high Tc cuprates Tl2201 and Tl2212 have been investigated using infrared spectroscopy. We observed the plasma frequencies for these two compounds at 27.8 and 25.6 cm-1 respectively, which we interpret as a Josephson resonance across the TlO blocking layers. No maximum in the temperature dependence of the c-axis conductivity was observed below Tc, indicating that even in the superconducting state a coherent quasi-particle contribution to the c-axis conductivity is absent or very weak, in contrast to the behaviour of the ab-plane conductivity.Comment: 4 pages, 3 figure

Illicit purchasing and use of flavour accessories after the European Union menthol cigarette ban: Findings from the 2020-2021 ITC Netherlands Surveys

Background The 2020 European Union (EU) menthol cigarette ban increased quitting among pre-ban menthol smokers in the Netherlands, but some reported continuing to smoke menthol cigarettes. This study examined three possible explanations for post-ban menthol use—(i) illicit purchasing, (ii) use of flavour accessories and (iii) use of non-menthol replacement brands marketed for menthol smokers. Methods Data were from the ITC Netherlands Cohort Surveys among adult smokers before the menthol ban (Wave 1: February–March 2020, N = 2067) and after the ban (Wave 2: September–November 2020, N = 1752; Wave 3: June–July 2021, N = 1721). Bivariate, logistic regression and generalized estimating equation model analyses were conducted on weighted data. Results Illicit purchasing remained low from pre-ban (2.4%, 95% CI: 1.8–3.2, Wave 1) to post-ban (1.7%, 1.2–2.5%, Wave 3), with no difference between menthol and non-menthol smokers from Wave 1 to Wave 3. About 4.4% of post-ban menthol smokers last purchased their usual brand outside of the EU and 3.6% from the internet; 42.5% of post-ban menthol smokers and 4.4% of smokers overall reported using flavour accessories, with greater odds among those aged 25–39 years vs. 55+ (aOR = 3.16, P = 0.002). Approximately 70% of post-ban smokers who reported using a menthol brand were actually using a non-menthol replacement brand. Conclusions There was no increase in illicit purchasing or of smuggling outside the EU among menthol and non-menthol smokers in the Netherlands 1 year after the EU menthol cigarette ban. Use of flavour accessories and non-menthol replacement brands best explain post-ban menthol use, suggesting the need to ban accessories and ensure industry compliance

In vivo evaluation of [F-18]FEAnGA-Me:a PET tracer for imaging beta-glucuronidase (beta-GUS) activity in a tumor/inflammation rodent model

Introduction: The PET tracer, 1-O-(4-(2-fluoroethyl-carbamoyloxymethyl)-2-nitrophenyl)-O-beta-D-glucopyronuronate ([F-18]FEAnGA), was recently developed for PET imaging of extracellularl beta-glucuronidase (beta-GUS). However,[F-18]FEAnGA exhibited rapid renal clearance, which resulted in a relatively low tracer uptake in the tumor. To improve the pharmacokinetics of [F-18]FEAnGA, we developed its more lipophilic methyl ester analog, [F-18]FEAnGA-Me. Methods: [F-18]FEAnGA-Me was obtained by alkylation of the O-protected glucuronide methyl ester precursor with [F-18]-fluoroethylamine ([F-18]FEA), followed by removal of the acetate protecting groups with NaOMe/MeOH. The PET tracer was evaluated by in vitro and in vivo studies. Results: [F-18]FEAnGA-Me was obtained in 5%-10% overall radiochemical yield. It is 10-fold less hydrophilic than [F-18]FEAnGA and it is stable in PBS and in the presence of beta-GUS for 1 h. However, in the presence of esterase or plasma [F-18]FEAnGA-Me is converted to [F-18]FEAnGA, and subsequently converted to [F-18]FEA by beta-GUS. MicroPET studies in Wistar rats bearing a C6 glioma and a sterile inflammation showed similar uptake in tumors after injection of either [F-18]FEAnGA-Me or [F-18]FEAnGA. Both tracers had a rapid two-phase clearance of total plasma radioactivity with a half-life of 1 and 8 min. The [F-18]FEAnGA fraction generated from [F-18]FEAnGA-Me by in vivo hydrolysis had a circulation half-life of 1 and 11 min in plasma. Similar distribution volume in the viable part of the tumor was found after injection of either [F-18]FEAnGA-Me or [F-18]FEAnGA. Conclusion: The imaging properties of [F-18]FEAnGA-Me were not significantly better than those of [F-18]FEAnGA. Therefore, other strategies should be applied in order to improve the kinetics of these tracers. (C) 2012 Elsevier Inc. All rights reserved

Generation and Characterization of Fmr1 Knockout Zebrafish

Fragile X syndrome (FXS) is one of the most common known causes of inherited mental retardation. The gene mutated in FXS is named FMR1, and is well conserved from human to Drosophila. In order to generate a genetic tool to study FMR1 function during vertebrate development, we generated two mutant alleles of the fmr1 gene in zebrafish. Both alleles produce no detectable Fmr protein, and produce viable and fertile progeny with lack of obvious phenotypic features. This is in sharp contrast to published results based on morpholino mediated knock-down of fmr1, reporting defects in craniofacial development and neuronal branching in embryos. These phenotypes we specifically addressed in our knock-out animals, revealing no significant deviations from wild-type animals, suggesting that the published morpholino based fmr1 phenotypes are potential experimental artifacts. Therefore, their relation to fmr1 biology is questionable and morpholino induced fmr1 phenotypes should be avoided in screens for potential drugs suitable for the treatment of FXS. Importantly, a true genetic zebrafish model is now available which can be used to study FXS and to derive potential drugs for FXS treatment

Thin superconducting disk with B-dependent Jc: Flux and current distributions

The critical state in a superconducting thin circular disk with an arbitrary magnetic field dependence of the critical sheet current, Jc(B), is analyzed. With an applied field Ba perpendicular to the disk, a set of coupled integral equations for the flux and current distributions is derived. The equations are solved numerically, and flux and current profiles are presented graphically for several commonly used Jc(B) dependences. It is shown that for small Ba the flux penetration depth can be described by an effective Bean model with a renormalized Jc entering the leading term. We argue that these results are qualitatively correct for thin superconductors of any shape. The results contrast the parallel geometry behavior, where at small Ba the B-dependence of the critical current can be ignored.Comment: RevTeX, 7 pages including 8 figure

Heritability of Body Mass Index: A comparison between the Netherlands and Spain.

A high body mass index (BMI) is commonly used as an index of overweight and obesity. There is persistent evidence of high heritability for variation in BMI, but the effects of common environment appear inconsistent across different European countries. Our objective was to compare genetic and environmental effects on BMI in a sample of twins from two different European countries with distinct population and cultural backgrounds. We analysed data of adult female twins from the Netherlands Twin Register (222 monozygotic [MZ] and 103 dizygotic [DZ] pairs) and the Murcia Twin Register (Spain; 202 MZ and 235 DZ pairs). BMI was based on self-reported weight and height. Dutch women were taller and heavier, but Spanish women had a significantly higher mean BMI. The age related weight increase was significantly stronger in the Spanish sample. Genetic analyses showed that genetic factors are the main contributors to variation in height, weight, and BMI, within both countries. For height and weight, estimates of genetic variances did not differ, but for height, the estimate for the environmental variance was significantly larger in Spanish women. For BMI, both the genetic and the environmental variance components were larger in Spanish than in Dutch women

Owning an overweight or underweight body: distinguishing the physical, experienced and virtual body

Our bodies are the most intimately familiar objects we encounter in our perceptual environment. Virtual reality provides a unique method to allow us to experience having a very different body from our own, thereby providing a valuable method to explore the plasticity of body representation. In this paper, we show that women can experience ownership over a whole virtual body that is considerably smaller or larger than their physical body. In order to gain a better understanding of the mechanisms underlying body ownership, we use an embodiment questionnaire, and introduce two new behavioral response measures: an affordance estimation task (indirect measure of body size) and a body size estimation task (direct measure of body size). Interestingly, after viewing the virtual body from first person perspective, both the affordance and the body size estimation tasks indicate a change in the perception of the size of the participant’s experienced body. The change is biased by the size of the virtual body (overweight or underweight). Another novel aspect of our study is that we distinguish between the physical, experienced and virtual bodies, by asking participants to provide affordance and body size estimations for each of the three bodies separately. This methodological point is important for virtual reality experiments investigating body ownership of a virtual body, because it offers a better understanding of which cues (e.g. visual, proprioceptive, memory, or a combination thereof) influence body perception, and whether the impact of these cues can vary between different setups

Effect of Hyperglycemia on Gene Expression during Early Organogenesis in Mice

BACKGROUND: Cardiovascular and neural malformations are common sequels of diabetic pregnancies, but the underlying molecular mechanisms remain unknown. We hypothesized that maternal hyperglycemia would affect the embryos most shortly after the glucose-sensitive time window at embryonic day (ED) 7.5 in mice. METHODS: Mice were made diabetic with streptozotocin, treated with slow-release insulin implants and mated. Pregnancy aggravated hyperglycemia. Gene expression profiles were determined in ED8.5 and ED9.5 embryos from diabetic and control mice using Serial Analysis of Gene Expression and deep sequencing. RESULTS: Maternal hyperglycemia induced differential regulation of 1,024 and 2,148 unique functional genes on ED8.5 and ED9.5, respectively, mostly in downward direction. Pathway analysis showed that ED8.5 embryos suffered mainly from impaired cell proliferation, and ED9.5 embryos from impaired cytoskeletal remodeling and oxidative phosphorylation (all P ≤ E-5). A query of the Mouse Genome Database showed that 20-25% of the differentially expressed genes were caused by cardiovascular and/or neural malformations, if deficient. Despite high glucose levels in embryos with maternal hyperglycemia and a ~150-fold higher rate of ATP production from glycolysis than from oxidative phosphorylation on ED9.5, ATP production from both glycolysis and oxidative phosphorylation was reduced to ~70% of controls, implying a shortage of energy production in hyperglycemic embryos. CONCLUSION: Maternal hyperglycemia suppressed cell proliferation during gastrulation and cytoskeletal remodeling during early organogenesis. 20-25% of the genes that were differentially regulated by hyperglycemia were associated with relevant congenital malformations. Unexpectedly, maternal hyperglycemia also endangered the energy supply of the embryo by suppressing its glycolytic capacity