Automated DBS Extraction Prior to Hilic/RP LC-MS/MS Target Screening of Drugs

This article describes a rapid LC-MS/MS target screening method based on an automated extraction of 5 mu L dried blood spots (DBS), two 5 min chromatographic runs on orthogonal phase columns (RP and Hilic) and a data dependent acquisition (DDA) of product ions spectra for the reliable identification of the detected compounds. The extraction step was performed in 2 min by using the LC autosampler itself in 96-well plates. This procedure was evaluated using 22 model compounds frequently encountered in forensic investigations, i.e., cocaine, benzodiazepines, amphetamines, opioids, antidepressants and antipsychotics. These investigations showed that even if the extraction step was reduced to a minimum, the extraction recoveries were satisfactory (median value of 40 %) and allowed for the detection of the model compounds in their therapeutic ranges, with the exception of morphine. Moreover, the use of two different chromatographic columns broadened the number of screening targets to those that behaved poorly under RP conditions, such as amphetamines or glucuronides, while keeping chromatographic gradients very short. This procedure was applied to 34 authentic post-mortem cases. It allowed the detection of 89 % of the compounds that were quantified in the routine procedures and the formal identification of 77 % of the compounds using their product ions spectra. These results were considered more than satisfactory compared to routine screening alone (GC-MS and LC-DAD, 55 % compound identification). The method described in this article is therefore a powerful approach for a fast, reliable and efficient target screening of drugs in forensic and clinical investigations

Dysfunction of homeostatic control of dopamine by astrocytes in the developing prefrontal cortex leads to cognitive impairments

Astrocytes orchestrate neural development by powerfully coordinating synapse formation and function and, as such, may be critically involved in the pathogenesis of neurodevelopmental abnormalities and cognitive deficits commonly observed in psychiatric disorders. Here, we report the identification of a subset of cortical astrocytes that are competent for regulating dopamine (DA) homeostasis during postnatal development of the prefrontal cortex (PFC), allowing for optimal DA-mediated maturation of excitatory circuits. Such control of DA homeostasis occurs through the coordinated activity of astroglial vesicular monoamine transporter 2 (VMAT2) together with organic cation transporter 3 and monoamine oxidase type B, two key proteins for DA uptake and metabolism. Conditional deletion of VMAT2 in astrocytes postnatally produces loss of PFC DA homeostasis, leading to defective synaptic transmission and plasticity as well as impaired executive functions. Our findings show a novel role for PFC astrocytes in the DA modulation of cognitive performances with relevance to psychiatric disorders

Search for Branons at LEP

We search, in the context of extra-dimension scenarios, for the possible existence of brane fluctuations, called branons. Events with a single photon or a single Z-boson and missing energy and momentum collected with the L3 detector in e^+ e^- collisions at centre-of-mass energies sqrt{s}=189-209$ GeV are analysed. No excess over the Standard Model expectations is found and a lower limit at 95% confidence level of 103 GeV is derived for the mass of branons, for a scenario with small brane tensions. Alternatively, under the assumption of a light branon, brane tensions below 180 GeV are excluded

Study of Z Boson Pair Production in e+e- Collisions at LEP at \sqrt{s}=189 GeV

The pair production of Z bosons is studied using the data collected by the L3 detector at LEP in 1998 in e+e- collisions at a centre-of-mass energy of 189 GeV. All the visible final states are considered and the cross section of this process is measured to be 0.74 +0.15 -0.14 (stat.) +/- 0.04 (syst.) pb. Final states containing b quarks are enhanced by a dedicated selection and their production cross section is found to be 0.18 +0.09 -0.07 (stat.) +/- 0.02 (syst.) pb. Both results are in agreement with the Standard Model predictions. Limits on anomalous couplings between neutral gauge bosons are derived from these measurements

Measurement of Exclusive rho^0 rho^0 Production in Two-Photon Collisions at High Q^2 at LEP

Exclusive rho rho production in two-photon collisions involving a single highly virtual photon is studied with data collected at LEP at centre-of-mass energies 89GeV < \sqrt{s} < 209GeV with a total integrated luminosity of 854.7pb^-1 The cross section of the process gamma gamma^* -> rho rho is determined as a function of the photon virtuality, Q^2 and the two-photon centre-of-mass energy, Wgg, in the kinematic region: 1.2GeV^2 < Q^2 < 30GeV^2 and 1.1GeV < Wgg < 3GeV

Formation of the ηc\eta_c in Two-Photon Collisions at LEP

The two-photon width $\Gamma_{\gamma\gamma}$ of the $\eta_c$ meson has been measured with the L3 detector at LEP. The $\eta_c$ is studied in the decay modes $\pi^+\pi^-\pi^+\pi^-$, $\pi^+\pi^-$K$^+$K$^-$, K$_s^0$K$^\pm\pi^\mp$, K$^+$K$^-\pi^{0}$, $\pi^+\pi^-\eta$, $\pi^+\pi^-\eta'$, and $\rho^+\rho^-$ using an integrated luminosity of 140 pb$^{-1}$ at $\sqrt{s} \simeq 91$ GeV and of 52 pb$^{-1}$ at $\sqrt{s} \simeq 183$ GeV. The result is $\Gamma_{\gamma\gamma}(\eta_c) = 6.9 \pm 1.7 (stat.) \pm 0.8 (sys.) \pm 2.0$(BR) keV. The $Q^2$ dependence of the $\eta_c$ cross section is studied for $Q^2 < 9$ GeV$^{2}$. It is found to be better described by a Vector Meson Dominance model form factor with a J-pole than with a $\rho$-pole. In addition, a signal of $29 \pm 11$ events is observed at the $\chi_c0$ mass. Upper limits for the two-photon widths of the $\chi_c0$, $\chi_c2$, and $\eta_c'$ are also given

Search for Scalar Leptons in e+e- collisions at \sqrt{s}=189 GeV

We report the result of a search for scalar leptons in e+e- collisions at 189 GeV centre-of-mass energy at LEP. No evidence for such particles is found in a data sample of 176 pb^{-1}. Improved upper limits are set on the production cross sections for these new particles. New exclusion contours in the parameter space of the Minimal Supersymmetric Standard Model are derived, as well as new lower limits on the masses of these supersymmetric particles. Under the assumptions of common gaugino and scalar masses at the GUT scale, we set an absolute lower limit on the mass of the lightest scalar electron of 65.5 Ge

Direct Observation of Longitudinally Polarised W Bosons

The three different helicity states of W bosons, produced in the reaction e+e- -> W+W- -> l nu q q~ are studied using leptonic and hadronic W decays at sqrt{s}=183GeV and 189GeV. The W polarisation is also measured as a function of the scattering angle between the W- and the direction of the e- beam. The analysis demonstrates that W bosons are produced with all three helicities, the longitudinal and the two transverse states. Combining the results from the two center-of-mass energies and with leptonic and hadronic W decays, the fraction of longitudinally polarised W bosons is measured to be 0.261 +/- 0.051(stat.) +/- 0.016(syst.) in agreement with the expectation from the Standard Model

Search for Low Scale Gravity Effects in e+e- Collisions at LEP

Recent theories propose that quantum gravity effects may be observable at LEP energies via gravitons that couple to Standard Model particles and propagate into extra spatial dimensions. The associated production of a graviton and a photon is searched for as well as the effects of virtual graviton exchange in the processes: e+e- -> gamma gamma, ZZ, WW, mu mu, tau tau, qq and ee No evidence for this new interaction is found in the data sample collected by the L3 detector at LEP at centre-of-mass energies up to 183 GeV. Limits close to 1 TeV on the scale of this new scenario of quantum gravity are set

Search for Charginos with a Small Mass Difference with the Lightest Supersymmetric Particle at \sqrt{s} = 189 GeV

A search for charginos nearly mass-degenerate with the lightest supersymmetric particle is performed using the 176 pb^-1 of data collected at 189 GeV in 1998 with the L3 detector. Mass differences between the chargino and the lightest supersymmetric particle below 4 GeV are considered. The presence of a high transverse momentum photon is required to single out the signal from the photon-photon interaction background. No evidence for charginos is found and upper limits on the cross section for chargino pair production are set. For the first time, in the case of heavy scalar leptons, chargino mass limits are obtained for any \tilde{\chi}^{+-}_1 - \tilde{\chi}^0_1 mass difference