Simultaneously measuring two ultrashort laser pulses on a single-shot using double-blind frequency-resolved optical gating

We demonstrate a simple self-referenced single-shot method for simultaneously measuring two different arbitrary pulses, which can potentially be complex and also have very different wavelengths. The method is a variation of cross-correlation frequency-resolved optical gating (XFROG) that we call double-blind (DB) FROG. It involves measuring two spectrograms, both of which are obtained simultaneously in a single apparatus. DB FROG retrieves both pulses robustly by using the standard XFROG algorithm, implemented alternately on each of the traces, taking one pulse to be ?known? and solving for the other. We show both numerically and experimentally that DB FROG using a polarization-gating beam geometry works reliably and appears to have no nontrivial ambiguities.

Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood–cerebrospinal-fluid drug-permeability barrier

The blood–brain barrier and a blood–cerebrospinal-fluid (CSF) barrier function together to isolate the brain from circulating drugs, toxins, and xenobiotics. The blood–CSF drug-permeability barrier is localized to the epithelium of the choroid plexus (CP). However, the molecular mechanisms regulating drug permeability across the CP epithelium are defined poorly. Herein, we describe a drug-permeability barrier in human and rodent CP mediated by epithelial-specific expression of the MDR1 (multidrug resistance) P glycoprotein (Pgp) and the multidrug resistance-associated protein (MRP). Noninvasive single-photon-emission computed tomography with 99mTc-sestamibi, a membrane-permeant radiopharmaceutical whose transport is mediated by both Pgp and MRP, shows a large blood-to-CSF concentration gradient across intact CP epithelium in humans in vivo. In rats, pharmacokinetic analysis with 99mTc-sestamibi determined the concentration gradient to be greater than 100-fold. In membrane fractions of isolated native CP from rat, mouse, and human, the 170-kDa Pgp and 190-kDa MRP are identified readily. Furthermore, the murine proteins are absent in CP isolated from their respective mdr1a/1b(−/−) and mrp(−/−) gene knockout littermates. As determined by immunohistochemical and drug-transport analysis of native CP and polarized epithelial cell cultures derived from neonatal rat CP, Pgp localizes subapically, conferring an apical-to-basal transepithelial permeation barrier to radiolabeled drugs. Conversely, MRP localizes basolaterally, conferring an opposing basal-to-apical drug-permeation barrier. Together, these transporters may coordinate secretion and reabsorption of natural product substrates and therapeutic drugs, including chemotherapeutic agents, antipsychotics, and HIV protease inhibitors, into and out of the central nervous system.

Cladistic association analysis of Y chromosome effects on alcohol dependence and related personality traits

Association between Y chromosome haplotype variation and alcohol dependence and related personality traits was investigated in a large sample of psychiatrically diagnosed Finnish males. Haplotypes were constructed for 359 individuals using alleles at eight loci (seven microsatellite loci and a nucleotide substitution in the DYZ3 alphoid satellite locus). A cladogram linking the 102 observed haplotype configurations was constructed by using parsimony with a single-step mutation model. Then, a series of contingency tables nested according to the cladogram hierarchy were used to test for association between Y haplotype and alcohol dependence. Finally, using only alcohol-dependent subjects, we tested for association between Y haplotype and personality variables postulated to define subtypes of alcoholism—antisocial personality disorder, novelty seeking, harm avoidance, and reward dependence. Significant association with alcohol dependence was observed at three Y haplotype clades, with significance levels of P = 0.002, P = 0.020, and P = 0.010. Within alcohol-dependent subjects, no relationship was revealed between Y haplotype and antisocial personality disorder, novelty seeking, harm avoidance, or reward dependence. These results demonstrate, by using a fully objective association design, that differences among Y chromosomes contribute to variation in vulnerability to alcohol dependence. However, they do not demonstrate an association between Y haplotype and the personality variables thought to underlie the subtypes of alcoholism.

Stable carbon, nitrogen and sulphur isotope analysis of permafrost preserved human hair from rescue excavations (2009, 2010) at the precontact site of Nunalleq, Alaska

Acknowledgments This work was funded by an Arts and Humanities Research Council (AH/K006029/1) grant awarded to Rick Knecht, Kate Britton and Charlotta Hillerdal (Aberdeen); an AHRC-LabEx award (AH/N504543/1) to KB, RK, Keith Dobney (Liverpool) and Isabelle Sidéra (Nanterre); the Carnegie Trust to the Universities of Scotland (travel grant to KB); and the Max Planck Institute for Evolutionary Anthropology. The onsite collection of samples was carried out by staff and students from the University of Aberdeen, volunteer excavators and the residents of Quinhagak. We had logistical and planning support for fieldwork by the Qanirtuuq Incorporated, Quinhagak, Alaska, and the people of Quinhagak, who we also thank for sampling permissions. Special thanks to Warren Jones and Qanirtuuq Incorporated (especially Michael Smith and Lynn Church), and to all Nunalleq project team members, in Aberdeen and at other institutions, particularly Charlotta Hillerdal and Edouard Masson-Maclean (Aberdeen) for comments on earlier versions of this manuscript, and also to Véronique Forbes, Ana Jorge, Carly Ameen and Ciara Mannion (Aberdeen) for their inputs. Thanks also to Michelle Alexander (York). Finally, thank you to Ian Scharlotta (Alberta) for inviting us to contribute to this special issue, to the Editor, and to three anonymous reviewers, whose suggestions and recommended changes to an earlier version of this manuscript greatly improved the paper.