Aromatic compounds such as toluene and xylene are major components of many fuels. Accurate kinetic mechanisms for the combustion of toluene are, however, incomplete, as they do not accurately model experimental results such as strain rates and ignition times and consistently underpredict conversion. Current kinetic mechanisms for toluene combustion neglect the reactions of the methylphenyl radicals, and we believe that this is responsible, in part, for the shortcomings of these models. We also demonstrate how methylphenyl radical formation is important in the combustion and pyrolysis of other alkyl-substituted aromatic compounds such as xylene and trimethylbenzene. We have studied the oxidation reactions of the methylphenyl radicals with O2 using computational ab initio and density functional theory methods. A detailed reaction submechanism is presented for the 2-methylphenyl radical + O2 system, with 16 intermediates and products. For each species, enthalpies of formation are calculated using the computational methods G3 and G3B3, with isodesmic work reactions used to minimize computational errors. Transition states are calculated at the G3B3 level, yielding high-pressure limit elementary rate constants as a function of temperature. For the barrierless methylphenyl + O2 and methylphenoxy + O association reactions, rate constants are determined from variational transition state theory. Multichannel, multifrequency quantum Rice-Ramsperger-Kassel (qRRK) theory, with master equation analysis for falloff, provides rate constants as a function of temperature and pressure from 800 to 2400 K and 1 x 10(-4) to 1 x 10(3) atm. Analysis of our results shows that the dominant pathways for reaction of the three isomeric methylphenyl radicals is formation of methyloxepinoxy radicals and subsequent ring opening to methyl-dioxo-hexadienyl radicals. The next most important reaction pathway involves formation of methylphenoxy radicals + O in a chain branching process. At lower temperatures, the formation of stabilized methylphenylperoxy radicals becomes significant. A further important reaction channel is available only to the 2-methylphenyl isomer, where 6-methylene-2,4-cyclohexadiene-1-one (ortho-quinone methide, o-QM) is produced via an intramolecular hydrogen transfer from the methyl group to the peroxy radical in 2-methylphenylperoxy, with subsequent loss of OH. The decomposition of o-QM to benzene + CO reveals a potentially important new pathway for the conversion of toluene to benzene during combustion. A number of the important products of toluene combustion proposed in this study are known to be precursors of polyaromatic hydrocarbons that are involved in soot formation. Reactions leading to the important unsaturated oxygenated intermediates identified in this study, and the further reactions of these intermediates, are not included in current aromatic oxidation mechanisms.

Kinetics for the chemical activation reaction of the OH radical with benzene and unimolecular dissociation of the adduct are analyzed using quantum Rice-Ramsperger-Kassel (QRRK) theory for k(E) and master equation analysis for pressure falloff. Thermochemical properties and reaction path parameters are determined by ab initio and density functional calculations. Molecular structures and vibration frequencies are determined at the B3LYP/6-31G(d,p) and MP2(full)/6-31G(d) levels, with single point calculations for the energy at the B3LYP/6-311++G(2df,p)//B3LYP/6-31G(d,p), composite methods of CBS-Q, CBS-QB3 and G3(MP2) and the G3 methods. The OH addition to benzene forms a chemically activated prereactive complex with a shallow well (ca. 3 kcal mol -1 ), which predominantly dissociates back to reactants. Additional reactions of the energized precomplex include stabilization, or forward reaction to form hydroxycyclohexadienyl radical, C • HDOH, which has a well depth of 16 kcal mol -1 . This C • HDOH adduct can either eliminate H atom to form phenol, undergo intramolecular addition of the radical to an unsaturated carbon site to form bicyclo[3.1.0]hexan-6-ol radical (I in Figure 2), or react back through the prereactive complex. The radical (I) can cleave a strained exocyclic, cyclopropane bond forming cyclopenta-2,4-dienylmethan-1-ol radical (II in Figure 2). Rate coefficients for reactions of the energized complex are obtained from canonical transition state theory. The high-pressure addition rate constant for OH + benzene f prereactive complex is calculated from variational transition state theory with a center-of-mass reaction coordinate approximation. A detailed mechanism with mass conservation and microscopic reversibility is assembled and used to identify the intermediates and products of the benzene + OH reaction for comparison with experiment. The prereactive complex has a small effect on the overall kinetics and can be considered negligible over the temperature and pressure range investigated. The most important product formation channel in the OH + benzene addition reaction system is formation of phenol plus H atom. Comparisons of our calculated rate constants with experimental data that exhibit complex temperature and pressure dependence of [OH] vs time shows very good agreement and illustrate that microscopic reversibility needs to be included in analysis of experimental data on this reaction system. The important products for benzene + OH addition are predicted to be C • HDOH and phenol + H. At 800 K, product formation from cyclopentadiene intermediates is at least 3 orders of magnitude lower than phenol + H.

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Structures and thermochemical properties, ∆H°f 298 , S°(T), and C p (T) (50 e T/K e 5000) of three ethers and the corresponding radicals were determined by ab initio and density functional calculations. Molecular structures and vibration frequencies were determined at the B3LYP/6-31G(d,p) and MP2/6-31G(d,p) levels, with single point calculations for the energy at the B3LYP/6-311+G(3df,2p) and MP2/6-311+G(2df,2p) levels, respectively, and with composite methods CBSQ and G3(MP2) with B3LYP/6-31G(d,p) and MP2/6-31G(d,p) optimized geometries. Enthalpies of formation (∆H°f 298 ) were determined at each calculation level using the group balance isodesmic reactions. Standard entropy, S°(T), and heat capacity, C p (T), from vibrational, translational, and external rotational contributions were calculated using the rigid-rotor-harmonic-oscillator approximation based on the vibration frequencies and structures obtained from the density functional study. Potential barriers for internal rotation were calculated at the B3LYP/6-31G(d) level, and hindered internal rotational contributions to entropy and heat capacity were calculated by summation over the energy levels obtained by direct diagonalization of the Hamiltonian matrix of hindered internal rotations. Evaluations of data from the isodesmic reactions at each calculation level results in the enthalpy of formation being -52.22 ( 0.84, -60.13 ( 0.94, and -67.78 ( 1.44 kcal/mol for methyl ethyl ether (CCOC), methyl isopropyl ether (C2COC), and methyl tert-butyl ether (C3COC), respectively. Standard enthalpies are -1.67 ( 0.98, -9.31 ( 2.18, and -7.93 ( 1.81 kcal/mol for methyl ethyl ether radicals, C • H 2 CH 2 OCH 3 (C • COC), CH 3 C • HOCH 3 (CC • OC), and CH 3 CH 2 OC • H 2 (CCOC • ), respectively. Standard enthalpies are -10.06 ( 0.85, -17.33 ( 2.38, and -16.75 ( 1.71 kcal/mol for methyl isopropyl ether radicals, C •, and (CH 3 ) 2 CHOC • H 2 (C2COC • ), respectively. Methyl tert-butyl ether radicals have enthalpies of -17.74 ( 1.13 and -24.54 ( 1.97 kcal/mol for C • H 2 (CH 3 ) 2 COCH 3 (C3 • COC) and (CH 3 ) 3 COC • H 2 (C3COC • ), respectively. Bond strengths on the ethers are in order C-H bond > C-C bond > central C-O bond > terminal C-O bond, with one exception of C-C bond energy for C2COC being slightly lower than that of the C-O bond (C2C-OC) by 0.5 kcal/mol. Thermodynamic properties of the O/C2 group and the ether gauche interaction term were determined for group additivity application. The hydrogen bond increment group values for ROCJ, RJCOC, and RCJOC were also derived.

Freezing of gait (FOG) is a disabling clinical phenomenon often found in patients with advanced Parkinson's disease (PD). FOG impairs motor function, causes falls and leads to loss of independence. Whereas dual tasking that distracts patients' attention precipitates FOG, auditory or visual cues ameliorate this phenomenon. The pathophysiology of FOG remains unclear. Previous studies suggest that the basal ganglia are involved in the generation of FOG. Investigation of the modulation of neuronal activities within basal ganglia structures during walking is warranted. To this end, we recorded local field potentials (LFP) from the subthalamic nucleus (STN) while PD patients performed single-task gait (ST) or walked while dual-tasking (DT). An index of FOG (iFOG) derived from trunk accelerometry was used as an objective measure to differentiate FOG-vulnerable gait from normal gait. Two spectral activities recorded from the STN region were associated with vulnerability to freezing. Greater LFP power in the low beta (15–21 Hz) and theta (5–8 Hz) bands were noted during periods of vulnerable gait in both ST and DT states. Whereas the elevation of low beta activities was distributed across STN, the increase in theta activity was focal and found in ventral STN and/or substantia nigra (SNr) in ST. The results demonstrate that low beta and theta band oscillations within the STN area occur during gait susceptible to freezing in PD. They also add to the evidence that narrow band ~18 Hz activity may be linked to FOG.

Background:Lactobacillus plantarum PS128 (PS128) is a specific probiotic, known as a psychobiotic, which has been demonstrated to alleviate motor deficits and inhibit neurodegenerative processes in Parkinson's disease (PD)-model mice. We hypothesize that it may also be beneficial to patients with PD based on the possible mechanism via the microbiome-gut-brain axis.Methods: This is an open-label, single-arm, baseline-controlled trial. The eligible participants were scheduled to take 60 billion colony-forming units of PS128 once per night for 12 weeks. Clinical assessments were conducted using the Unified Parkinson's Disease Rating Scale (UPDRS), modified Hoehn and Yahr scale, and change in patient “ON-OFF” diary recording as primary outcome measures. The non-motor symptoms questionnaire, Beck depression inventory-II, patient assessment of constipation symptom, 39-item Parkinson's Disease Questionnaire (PDQ-39), and Patient Global Impression of Change (PGI-C) were assessed as secondary outcome measures.Results: Twenty-five eligible patients (32% women) completed the study. The mean age was 61.84 ± 5.74 years (range, 52–72), mean disease duration was 10.12 ± 2.3 years (range, 5–14), and levodopa equivalent daily dosage was 1063.4 ± 209.5 mg/daily (range, 675–1,560). All patients remained on the same dosage of anti-parkinsonian and other drugs throughout the study. After 12 weeks of PS128 supplementation, the UPDRS motor scores improved significantly in both the OFF and ON states (p = 0.004 and p = 0.007, respectively). In addition, PS128 intervention significantly improved the duration of the ON period and OFF period as well as PDQ-39 values. However, no obvious effect of PS128 on non-motor symptoms of patients with PD was observed. Notably, the PGI-C scores improved in 17 patients (68%). PS128 intervention was also found to significantly reduce plasma myeloperoxidase and urine creatinine levels.Conclusion: The present study demonstrated that PS128 supplementation for 12 weeks with constant anti-parkinsonian medication improved the UPDRS motor score and quality of life of PD patients. We suggest that PS128 could serve as a therapeutic adjuvant for the treatment of PD. In the future, placebo-controlled studies are needed to further support the efficacy of PS128 supplementation.Clinical Trial Registration:https://clinicaltrials.gov/, identifier: NCT04389762.

There are very few conditions that present with dopa-responsive juvenile parkinsonism. We present two such children with neuronal intranuclear inclusion disease (NIID) who had an initial good levodopa response that was soon complicated by disabling dopa-induced dyskinesia. One child was diagnosed by rectal biopsy in life, and the other diagnosis was confirmed at postmortem. In this patient, dopamine transporter imaging showed severely decreased binding of the radiotracer in the striatum on both sides. Bilateral subthalamic deep brain stimulation in this patient produced initial improvement, but this was not sustained. Both patients died within 10 years of symptom onset. As well as levodopa responsiveness with rapid onset of dyskinesia, clues to the diagnosis of NIID in patients presenting with parkinsonism include the presence of gaze-evoked nystagmus, early onset dysarthria and dysphagia and oculogyric crises. Differential diagnosis of clinical symptoms and neuropathological findings are discussed including the approach to rectal biopsy for early diagnosis.

To gain insight into the mechanisms and kinetics of 2-azido-N,N-dimethylethanamine's (DMAZ's) thermal decomposition postulated reaction paths were simulated with ab initio and density functional theory quantum chemistry models. Four reaction types were modeled: (i) spin-allowed and spin-forbidden paths involving N-N(2) bond fission and nitrene formation, (ii) HN(3) elimination with the formation of (dimethylamino)ethylene, (iii) N-N(2) bond fission with the formation of molecules with three- or four-membered heterocyclic rings, and (iv) simple scission of C-H, C-N, and C-C bonds. The geometries of stationary points of the reactions were obtained with a MPWB1K/6-31+G(d,p) model. To locate and model the geometries of minimum energy intersystem crossing points for triplet nitrene formation and isomerization, unrestricted broken spin symmetry calculations were performed. Employed to model an analogous path for methyl azide's decomposition, this approach was found to yield results similar to those obtained with a CASSCF(10,8)/aug-cc-pVDZ model. Of the four reaction types studied, N-N(2) bond fissions with singlet or triplet nitrene formation were found to have the lowest barriers. Barriers for paths to cyclic products were found to be 2-4 kcal/mol higher. Kinetic rate expressions for individual paths were derived from the quantum chemistry results, and spin-allowed nitrene formation was found to be dominant at all temperatures and pressures examined. The expression 2.69 × 10(9) (s(-1))T(1.405) exp(-39.0 (kcal/mol)/RT), which was derived from QCISD(T)/6-31++G(3df,2p)//MPWB1K/6-31+G(d,p) results, was found to be representative of this reaction's gas-phase rate. Adjusted on the basis of results from self-consistent reaction field models to account for solvation by n-dodecane, the expression became 1.11 × 10(9) (s(-1))T(1.480) exp(-37.6 (kcal/mol)/RT). Utilizing this result and others derived in the study, a model of the decomposition of n-dodecane-solvated DMAZ was constructed, and it generated simulations that well-reproduce previously published measured data for the process.