Decays of Non-strange Negative Parity Baryons in the 1/Nc Expansion

The decays of non-strange negative parity baryons via the emission of single $\pi$ and $\eta$ mesons are analyzed in the framework of the $1/N_c$ expansion. A basis of spin-flavor operators for the partial wave amplitudes is established to order $1/N_c$ and the unknown effective coefficients are determined by fitting to the S- and D-wave partial widths as provided by the Particle Data Group. A set of relations between widths that result at the leading order, i.e. order $N_c^0$, is given and tested with the available data. Up to a few exceptions, a good description of the partial decays widths is already obtained at that order. Because of the rather large errors in the empirical input data the next to leading order fit fails to pin down with satisfactory accuracy the subleading effective coefficients. The hierarchy expected from the $1/N_c$ expansion is reflected in the results.Comment: 24 pages, 8 table

LC–MS/MS determination of carbamathione in microdialysis samples from rat brain and plasma

A selective liquid chromatography–tandem mass spectrometric (LC–MS/MS) method was developed for the determination of S-(N, N-diethylcarbamoyl) glutathione (carbamathione) in microdialysis samples from rat brain and plasma. S-(N, N-Diethylcarbamoyl) glutathione (carbamathione) is a metabolite of disulfiram. This metabolite may be responsible for disulfiram’s effectiveness in the treatment of cocaine dependence. An analytical method using liquid chromatography–tandem mass spectrometric (LC–MS/MS) was developed to determine carbamathione in vivo using microdialysis sampling from rat brain and plasma. Chromatographic separations were carried out on an Alltech Altima C-18 (50 mm long × 2.1 mm i.d., 3 μm particles) analytical column at a flow rate of 0.3 ml/min. Solvent A consisted of 10 mM ammonium formate, methanol, and formic acid (99:1:0.06, v/v/v). Solvent B consisted of methanol, 10 mM ammonium formate and formic acid (99:1:0.06, v/v/v). A 20 min linear gradient from 95% aqueous to 95% organic was used. Tandem mass spectra were acquired on a Micromass Quattro Ultima “triple” quadrupole mass spectrometer equipped with an ESI interface. Quantitative mass spectrometric analysis was conducted in positive ion mode selected reaction monitoring (SRM) mode looking at the transition of m/z 407–100 and 175 for carbamathione and m/z 392–263 for the internal standard S-hexyl glutathione. The simultaneous collection of microdialysate from blood and brain was used to monitor carbamathione concentrations centrally and peripherally. Good linearity was obtained over a concentration range of 0.25–10,000 nM. The lowest limit of quantification (LLOQ) was determined to be 1 nM and the lowest limit of detection (LLOD) was calculated to be 0.25 nM. Intra- and inter-day accuracy and precision were determined and for all the samples evaluated, the variability was less that 10% (R.S.D.)

Resting-state functional connectivity predicts the ability to adapt to robot-mediated force fields

Motor deficits are common outcomes of neurological conditions such as stroke. In order to design personalised motor rehabilitation programmes such as robot-assisted therapy, it would be advantageous to predict how a patient might respond to such treatment. Spontaneous neural activity has been observed to predict differences in the ability to learn a new motor behaviour in both healthy and stroke populations. This study investigated whether spontaneous resting-state functional connectivity could predict the degree of motor adaptation of right (dominant) upper limb reaching in response to a robot-mediated force field. Spontaneous neural activity was measured using resting-state electroencephalography (EEG) in healthy adults before a single session of motor adaptation. The degree of beta frequency (β; 15–25 Hz) resting-state functional connectivity between contralateral electrodes overlying the left primary motor cortex (M1) and the anterior prefrontal cortex (aPFC) could predict the subsequent degree of motor adaptation. This result provides novel evidence for the functional significance of resting-state synchronization dynamics in predicting the degree of motor adaptation in a healthy sample. This study constitutes a promising first step towards the identification of patients who will likely gain most from using robot-mediated upper limb rehabilitation training based on simple measures of spontaneous neural activity

S-(N, N-diethylcarbamoyl)glutathione (carbamathione), a disulfiram metabolite and its effect on nucleus accumbens and prefrontal cortex dopamine, GABA, and glutamate: A microdialysis study

Disulfiram (DSF), used for the treatment of alcohol use disorders (AUDs) for over six decades, most recently has shown promise for treating cocaine dependence. Although DSF’s mechanism of action in alcohol abuse is due to the inhibition of liver mitochondrial aldehyde dehydrogenase (ALDH2), its mechanism of action in the treatment of cocaine dependence is unknown. DSF is a pro-drug, forming a number of metabolites each with discrete pharmacological actions. One metabolite formed during DSF bioactivation is S-(N, N-diethylcarbamoyl) glutathione (carbamathione) (carb). We previously showed that carb affects glutamate binding. In the present studies, we employed microdialysis techniques to investigate the effect of carb administration on dopamine (DA), GABA, and glutamate (Glu) in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), two brain regions implicated in substance abuse dependence. The effect of DSF on DA, GABA, and Glu in the NAc also was determined. Both studies were carried out in male rats. Carb (20, 50, 200 mg/kg i v) in a dose-dependent manner increased DA, decreased GABA, and had a biphasic effect on Glu, first increasing and then decreasing Glu in both the NAc and mPFC. These changes all occurred concurrently. After carb administration, NAc and mPFC carb, as well as carb in plasma, were rapidly eliminated with a half-life for each approximately 4 min, while the changes in DA, GABA, and GLu in the NAc and mPFC persisted for approximately two hours. The maximal increase in carb (Cmax) in the NAc and mPFC after carb administration was dose-dependent, as was the area under the curve (AUC). DSF (200 mg/kg i p) also increased DA, decreased GABA, and had a biphasic effect on Glu in the NAc similar to that observed in the NAc after carb administration. When the cytochrome P450 inhibitor N-benzylimidazole (NBI) (20 mg/kg i p) was administered before DSF dosing, no carb could be detected in the NAc and plasma and also no changes in NAc DA, GABA, and GLu occurred. Changes in these neurotransmitters occurred only if carb was formed from DSF. When NBI was administered prior to dosing with carb, the increase in DA, decrease in GABA, and biphasic effect on GLu was similar to that seen after dosing with carb only. The i p or i v administration of carb showed similar changes in DA, GABA, and GLu, except the time to reach Cmax for DA as well as the changes in GABA, and GLu after i p administration occurred later. The elimination half-life of carb and the area under the curve (AUC) were similar after both routes of administration. It is concluded that carb must be formed from DSF before any changes in DA, GABA, and GLu in the NAc and mPFC are observed. DSF and carb, when administered to rats, co-release DA, GABA, and GLu. Carb, once formed can cross the blood brain barrier and enter the brain. Although inhibition of liver ALDH2 is the accepted mechanism for DSF’s action in treating AUDs, the concurrent changes in DA, GABA, and GLu in the NAc and mPFC after DSF administration suggest that changes in these neurotransmitters as a potential mechanism of action not only for AUDs, but also for cocaine dependence cannot be excluded

LC-MS/MS Method for the determination of carbamathione in human plasma

Liquid chromatography-tandem mass spectrometry methodology is described for the determination of S-(N,N-diethylcarbamoyl)glutathione (carbamathione) in human plasma samples. Sample preparation consisted of a straightforward perchloric acid medicated protein precipitation, with the resulting supernatant containing the carbamathione (recovery ∼98%). For optimized chromatography/mass spec detection a carbamathione analog, S-(N,N-di-i-propylcarbamoyl)glutathione, was synthesized and used as the internal standard. Carbamathione was found to be stable over the pH 1-8 region over the timeframe necessary for the various operations of the analytical method. Separation was accomplished via reversed-phase gradient elution chromatography with analyte elution and re-equilibration accomplished within 8 minutes. Calibration was established and validated over the concentration range of 0.5-50 nM, which is adequate to support clinical investigations. Intra- and inter-day accuracy and precision determined and found to be < 4% and < 10%, respectively. The methodology was utilized to demonstrate the carbamathione plasma-time profile of a human volunteer dosed with disulfiram (250 mg/d). Interestingly, an unknown but apparently related metabolite was observed with each human plasma sample analyzed

Masses of the 70- Baryons in Large Nc QCD

The masses of the negative parity 70-plet baryons are analyzed in large N_c QCD to order 1/N_c and to first order in SU(3) symmetry breaking. The existing experimental data are well reproduced and twenty new observables are predicted. The leading order SU(6) spin-flavor symmetry breaking is small and, as it occurs in the quark model, the subleading in 1/N_c hyperfine interaction is the dominant source of the breaking. It is found that the Lambda(1405) and Lambda(1520) are well described as three-quark states and spin-orbit partners. New relations between splittings in different SU(3) multiplets are found.Comment: 11 pages; references were added and a couple of improvements to the text were mad

N-Acetyl-S-(N,N-diethylcarbamoyl) cysteine in rat nucleus accumbens, medial prefrontal cortex, and in RAT and human plasma after disulfiram administration

Disulfiram (DSF), a treatment for alcohol use disorders, has shown some clinical effectiveness in treating addiction to cocaine, nicotine, and pathological gambling. The mechanism of action of DSF for treating these addictions is unclear but it is unlikely to involve the inhibition of liver aldehyde dehydrogenase (ALDH2). DSF is a pro-drug and forms a number of metabolites, one of which is N-acetyl-S-(N,N-diethylcarbamoyl) cysteine (DETC-NAC). Here we describe a LCMS/MS method on a QQQ type instrument to quantify DETC-NAC in plasma and intracellular fluid from mammalian brain. An internal standard, the N,N-di-isopropylcarbamoyl homolog (MIM: 291 > 128) is easily separable from DETC-NAC (MIM: 263 > 100) on C18 RP media with a methanol gradient. The method's linear range is 0.5–500 nM from plasma and dialysate salt solution with all precisions better than 10% RSD. DETC-NAC and internal standards were recovered at better than 95% from all matrices, perchloric acid precipitation (plasma) or formic acid addition (salt) and is stable in plasma or salt at low pH for up to 24 h. Stability is observed through three freeze-thaw cycles per day for 7 days. No HPLC peak area matrix effect was greater than 10%. A human plasma sample from a prior analysis for S-(N,N-diethylcarbamoyl) glutathione (CARB) was found to have DETC NAC as well. In other human plasma samples from 62.5 mg/d and 250mg/d dosing, CARB concentration peaks at 0.3 and 4 nM at 3 h followed by DETC-NAC peaks of 11 and 70 nM 2 h later. Employing microdialysis sampling, DETC-NAC levels in the nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and plasma of rats treated with DSF reached 1.1, 2.5 and 80 nM at 6 h. The correlation between the appearance and long duration of DETC-NAC concentration in rat brain and the persistence of DSF-induced changes in neurotransmitters observed by Faiman et al. (Neuropharmacology, 2013, 75C, 95–105) is discussed

Low-lying spectrum of the Y-string three-quark potential using hyper-spherical coordinates

We calculate the energies of three-quark states with definite permutation symmetry (i.e. of SU(6) multiplets) in the N=0,1,2 shells, confined by the Y-string three-quark potential. The exact Y-string potential consists of one, so-called three-string term, and three angle-dependent two-string terms. Due to this technical complication we treat the problem at three increasingly accurate levels of approximation: 1) the (approximate) three-string potential expanded to first order in trigonometric functions of hyper-spherical angles; 2) the (approximate) three-string potential to all orders in the power expansion in hyper-spherical harmonics, but without taking into account the transition(s) to two-string potentials; 3) the exact minimal-length string potential to all orders in power expansion in hyper-spherical harmonics, and taking into account the transition(s) to two-string potentials. We show the general trend of improvement %convergence of these approximations: The exact non-perturbative corrections to the total energy are of the order of one per cent, as compared with approximation 2), yet the exact energy differences between the $[20,1^{+}], [70,2^{+}], [56,2^{+}], [70,0^{+}]$-plets are shifted to 2:2:0.9, from the Bowler and Tynemouth separation rule 2:2:1, which is obeyed by approximation 2) at the one per cent level. The precise value of the energy separation of the first radial excitation ("Roper") $[56^{\prime},0^{+}]$-plet from the $[70,1^{-}]$-plet depends on the approximation, but does not become negative, i.e. the "Roper" remains heavier than the odd-parity $[70,1^{-}]$-plet in all of our approximations.Comment: 19 pages, 6 figure

Decays of ℓ=1\ell=1 Baryons --- Quark Model versus Large-NcN_c

We study nonleptonic decays of the orbitally excited, \su6 \rep{70}-plet baryons in order to test the hypothesis that the successes of the nonrelativistic quark model have a natural explanation in the large-$N_c$ limit of QCD. By working in a Hartree approximation, we isolate a specific set of operators that contribute to the observed s- and d-wave decays in leading order in $1/N_c$. We fit our results to the current experimental decay data, and make predictions for a number of allowed but unobserved modes. Our tentative conclusion is that there is more to the nonrelativistic quark model of baryons than large-$N_c$.Comment: LaTeX 49pp. (38 pp. landscape), PicTex, PrePicTex, PostPicTex required for 3 figures, Harvard Preprint HUTP-94/A008. (Two additional operators are included, but conclusions are unchanged.