Screening for UBE3A gene mutations in a group of Angelman syndrome patients selected according to non-stringent clinical criteria

Abstract.: The Angelman syndrome (AS) is caused by genetic abnormalities affecting the maternal copy of chromosome region 15q12. Until recently, the molecular diagnosis of AS relied on the detection of either a deletion at 15q11-13, a paternal uniparental disomy (UPD) for chromosome 15 or imprinting mutations. A fourth class of genetic defects underlying AS was recently described and consists of mutations of the UBE3A gene. The vast majority of mutations reported so far are predicted to cause major disruptions at the protein level. It is unclear whether mutations with less drastic consequences for the gene product could lead to milder forms of AS. We report on our results obtained by screening 101 clinically diagnosed AS patients for mutations in the UBE3A gene. Non-stringent clinical criteria were purposely applied for inclusion of AS patients in this study. The mutation search was carried out by single-strand conformation polymorphism (SSCP), and SSCP/restriction fragment length polymorphism (RFLP) analyses and revealed five novel UBE3A gene mutations as well as three different polymorphisms. All five mutations were detected in patients with typical features of AS and are predicted to cause frameshifts in four cases and the substitution of a highly conserved residue in the fifth. The results we obtained add to the as yet limited number of reports concerning UBE3A gene mutations. Important aspects that emerge from the data available to date is that the four classes of genetic defects known to underlie AS do not appear to cover all cases. The genetic defect underlying approximately 10% of AS cases, including some familial cases, remains unknow

Sympathetic cooling in a mixture of diamagnetic and paramagnetic atoms

We have experimentally realized a hybrid trap for ultracold paramagnetic rubidium and diamagnetic ytterbium atoms by combining a bichromatic optical dipole trap for ytterbium with a Ioffe-Pritchard-type magnetic trap for rubidium. In this hybrid trap, sympathetic cooling of five different ytterbium isotopes through elastic collisions with rubidium was achieved. A strong dependence of the interspecies collisional cross section on the mass of the ytterbium isotope was observed.Comment: 4 pages, 4 figure

Spatial separation in a thermal mixture of ultracold 174^{174}Yb and 87^{87}Rb atoms

We report on the observation of unusually strong interactions in a thermal mixture of ultracold atoms which cause a significant modification of the spatial distribution. A mixture of $^{87}$Rb and $^{174}$Yb with a temperature of a few $\mu$K is prepared in a hybrid trap consisting of a bichromatic optical potential superimposed on a magnetic trap. For suitable trap parameters and temperatures, a spatial separation of the two species is observed. We infer that the separation is driven by a large interaction strength between $^{174}$Yb and $^{87}$Rb accompanied by a large three-body recombination rate. Based on this assumption we have developed a diffusion model which reproduces our observations

Lifetime Measurement of the 6s Level of Rubidium

We present a lifetime measurements of the 6s level of rubidium. We use a time-correlated single-photon counting technique on two different samples of rubidium atoms. A vapor cell with variable rubidium density and a sample of atoms confined and cooled in a magneto-optical trap. The 5P_{1/2} level serves as the resonant intermediate step for the two step excitation to the 6s level. We detect the decay of the 6s level through the cascade fluorescence of the 5P_{3/2} level at 780 nm. The two samples have different systematic effects, but we obtain consistent results that averaged give a lifetime of 45.57 +- 0.17 ns.Comment: 10 pages, 9 figure

R Markdown: Integrating A Reproducible Analysis Tool into Introductory Statistics

Nolan and Temple Lang argue that “the ability to express statistical computations is an es- sential skill.” A key related capacity is the ability to conduct and present data analysis in a way that another person can understand and replicate. The copy-and-paste workflow that is an artifact of antiquated user-interface design makes reproducibility of statistical analysis more difficult, especially as data become increasingly complex and statistical methods become increasingly sophisticated. R Markdown is a new technology that makes creating fully-reproducible statistical analysis simple and painless. It provides a solution suitable not only for cutting edge research, but also for use in an introductory statistics course. We present experiential and statistical evidence that R Markdown can be used effectively in introductory statistics courses, and discuss its role in the rapidly-changing world of statistical computation

Sphingosine 1-phosphate modulates antigen capture by murine langerhans cells via the S1P2 receptor subtype

Dendritic cells (DCs) play a pivotal role in the development of cutaneous contact hypersensitivity (CHS) and atopic dermatitis as they capture and process antigen and present it to T lymphocytes in the lymphoid organs. Recently, it has been indicated that a topical application of the sphingolipid sphingosine 1-phosphate (S1P) prevents the inflammatory response in CHS, but the molecular mechanism is not fully elucidated. Here we indicate that treatment of mice with S1P is connected with an impaired antigen uptake by Langerhans cells (LCs), the initial step of CHS. Most of the known actions of S1P are mediated by a family of five specific G protein-coupled receptors. Our results indicate that S1P inhibits macropinocytosis of the murine LC line XS52 via S1P2 receptor stimulation followed by a reduced phosphatidylinositol 3-kinase (PI3K) activity. As down-regulation of S1P2 not only diminished S1P-mediated action but also enhanced the basal activity of LCs on antigen capture, an autocrine action of S1P has been assumed. Actually, S1P is continuously produced by LCs and secreted via the ATP binding cassette transporter ABCC1 to the extracellular environment. Consequently, inhibition of ABCC1, which decreased extracellular S1P levels, markedly increased the antigen uptake by LCs. Moreover, stimulation of sphingosine kinase activity, the crucial enzyme for S1P formation, is connected not only with enhanced S1P levels but also with diminished antigen capture. These results indicate that S1P is essential in LC homeostasis and influences skin immunity. This is of importance as previous reports suggested an alteration of S1P levels in atopic skin lesions

Effect of the unpolarized spin state in spin-correlation measurement of two protons produced in the 12C(d,2He) reaction

In this note we discuss the effect of the unpolarized state in the spin-correlation measurement of the $^1S_0$ two-proton state produced in 12C(d,2He) reaction at the KVI, Groningen. We show that in the presence of the unpolarized state the maximal violation of the CHSH-Bell inequality is lower than the classical limit if the purity of the state is less than $\sim \verb+70$. In particular, for the KVI experiment the violation of the CHSH-Bell inequality should be corrected by a factor $\sim\verb+10$ from the pure $^1S_0$ state.Comment: 6 pages, to appear in J. Phys.

The analysis of European lacquer : optimization of thermochemolysis temperature of natural resins

In order to optimize chromatographic analysis of European lacquer, thermochemolysis temperature was evaluated for the analysis of natural resins. Five main ingredients of lacquer were studied: sandarac, mastic, colophony, Manila copal and Congo copal. For each, five temperature programs were tested: four fixed temperatures (350, 480, 550, 650 degrees C) and one ultrafast thermal desorption (UFD), in which the temperature rises from 350 to 660 degrees C in 1 min. In total, the integrated signals of 27 molecules, partially characterizing the five resins, were monitored to compare the different methods. A compromise between detection of compounds released at low temperatures and compounds formed at high temperatures was searched. 650 degrees C is too high for both groups, 350 degrees C is best for the first, and 550 degrees C for the second. Fixed temperatures of 480 degrees C or UFD proved to be a consensus in order to detect most marker molecules. UFD was slightly better for the molecules released at low temperatures, while 480 degrees C showed best compounds formed at high temperatures