262 research outputs found
SYNTHESIS OF C-GLYCOSYL AMINO ACIDS AS STABLE BUILDING BLOCKS FOR MODIFIED GLYCOPEPTIDE SYNTHESIS
No full textIn this thesis, we have studied and synthesized new class of C-glycosly amino acids whose structure features a
hetrocycle ring holding the carbohydrate and the amino acid fragments. Pyridine and tetrazole rings were used as
hetrocycle linkers in this project. This class of C-glycosyl amino acids is of interest as new chealtors and as building
building blocks for cotranslational glycopeptides synthesis. In the first part, C-Glycosylmethyl pyridylalanines were
synthesized via thermally induced Hantzsch-type cyclocondensation using an aldehyde-ketoester-enamino ester system.
To one of these reagents was attached a C-glycosyl residue, while to another was bound an amino acid fragment. In a
one-pot optimized methodology, the dihydropyridine was not isolated while its purification was carried out by removal
of unreacted material and side products using polymer-supported scavengers. Then the dihydropyridine (mixture of
diastereoisomers) was oxidized by a polymer-bound oxidant to give the target pyridine bearing the two bioactive
residues. In this way, a range of eight compounds (58-68% yield) was prepared in which the elements of diversity were
(i) the gluco and galacto configurations of the pyranose ring, (ii) the α- and β-configurations at the anomeric center, and
(iii) the positions of the carbohydrate and amino acid sectors in the pyridine ring. The orthogonal functional group
protection in these amino acids allowed their easy incorporation into oligopeptides via sequential amino and carboxylic
group coupling.
In the second part, tetrazole moiety was constructed via Huisgen 1,3-dipolar cycloaddition between nitriles and organic
azides. Two sets of compounds have been prepared, one being constituted of C-galactosyl and C-ribosyl O-tetrazolyl
serines, while the other contains S-tetrazolyl cysteine derivatives. In both cases, the synthetic scheme involved a twostep
route: the first one being the thermal cycloaddition of a sugar azide with p-toluensulfonyl cyanide (TsCN) to give a
1-substituted 5-sulfonyl tetrazole and the second the replacement of the tosyl group with a serine or cysteine residue.
For the high efficiency and operational simplicity, the azide-TsCN cycloaddition appears to be a true click process.
Finally, one of the amino acids prepared was incorporated into a tripeptid
Development of a Computational Model of Respiratory Mechanics in Mechanical Ventilation
No full textTechnical Medicine | Sensing and Stimulatio
Quick and Sensitive UPLC-ESI-MS/MS Method for Simultaneous Estimation of Sofosbuvir and Its Metabolite in Human Plasma
No full textA simple, fast and highly sensitive RP-UPLC-MS/MS method was developed and validated for the simultaneous determination of sofosbuvir (SR) and its metabolite GS331007 in human plasma using ketotifen as an internal standard (IS). The separation was achieved on Acquity UPLC BEH C18 (50 × 2.1 mm, i.d. 1.7 µm, Waters, USA) column using acetonitrile:5 mM ammonium formate:0.1% formic acid (85:15:0.1% v/v/v) as a mobile phase at a flow rate of 0.35 mL/min in an isocratic elution. The Xevo TQD UPLC-MS/MS was operated under the multiple-reaction monitoring mode using positive electrospray ionization. Extraction with dichloromethane was used in the sample preparation. Method validation was performed as per the Food and Drug Administration (FDA) guidelines and the calibration curves of the proposed method were found to be linear in the range of 1–1000 ng/mL for SR and in the range of 10–1500 ng/mL for its metabolite (GS331007) with an elution time of 1.83 min. All validation parameters were within the acceptable range according to the bioanalytical methods validation guidelines. Furthermore, the obtained results of matrix effects indicate that ion suppression or enhancement from human plasma components was negligible under the optimized conditions. The proposed method can be applied in high-throughput analysis required for pharmacokinetic and bioequivalence studies in human samples
Measurement of the CP-violating phase phi(s) in the B-s(0) -> J/psi phi(1020) -> mu(+)mu-K+K- channel in proton-proton collisions at root s=13 TeV
No full textThe CP-violating weak phase ?s and the decay width difference ??s between the light and heavy B0s mass eigenstates are measured with the CMS detector at the LHC in a sample of 48 500 reconstructed B0s? J/I) d (1020) ?11+11? K+K? events. The measurement is based on a data sample corresponding to an integrated luminosity of 96.4 fb?1, collected in proton-proton collisions at ?s = 13 TeV in 2017?2018. To extract the values of ?s and ??s, a time-dependent and flavor-tagged angular analysis of the 11+11?K+K? final state is performed. The analysis employs a dedicated tagging trigger and a novel opposite-side muon flavor tagger based on machine learning techniques. The measurement yields ?s = ?11 ?50 (stat) ? 10 (syst) mrad and ??s = 0.114 ? 0.014 (stat)? 0.007 (syst) ps?1, in agreement with the standard model predictions. When combined with the previous CMS measurement at ?s = 8 TeV, the following values are obtained: ?s = ?21 ? 44 (stat) ? 10 (syst) mrad, ??s = 0.1032 ? 0.0095 (stat) ? 0.0048 (syst) ps?1, a significant improvement over the 8 TeV result. ? 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY licens
Alkaline Phosphatases: Biochemistry, Functions, and Measurement
No full textAlkaline phosphatases (ALPs) are a group of isoenzymes, situated on the external layer of the cell membrane; they catalyze the hydrolysis of organic phosphate esters present in the extracellular space. Zinc and magnesium are significant co-factors for the biological activity of these enzymes. Although ALPs are available in various body tissues and have distinct physiochemical properties, they are true isoenzymes since they catalyze a similar reaction. In the liver, ALP is cytosolic and present in the canalicular membrane of the hepatocytes. ALPs are available in placenta, ileal mucosa, kidney, bone, and liver. However, most of the ALPs in serum (over 80%) are delivered from liver and bone and in more modest quantities from the intestines. Despite the fact that alkaline phosphatases are found in numerous tissues all through the body, their exact physiological function remains largely unknown. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature
Prevalence, incidence and risk factors of epilepsy in older children in rural Kenya.
No full textBACKGROUND: There is little data on the burden or causes of epilepsy in developing countries, particularly in children living in sub-Saharan Africa. METHODS: We conducted two surveys to estimate the prevalence, incidence and risk factors of epilepsy in children in a rural district of Kenya. All children born between 1991 and 1995 were screened with a questionnaire in 2001 and 2003, and those with a positive response were then assessed for epilepsy by a clinician. Active epilepsy was defined as two or more unprovoked seizures with one in the last year. RESULTS: In the first survey 10,218 children were identified from a census, of whom 110 had epilepsy. The adjusted prevalence estimates of lifetime and active epilepsy were 41/1000 (95% CI: 31-51) and 11/1000 (95% CI: 5-15), respectively. Overall two-thirds of children had either generalized tonic-clonic and/or secondary generalized seizures. A positive history of febrile seizures (OR=3.01; 95% CI: 1.50-6.01) and family history of epilepsy (OR=2.55; 95% CI: 1.19-5.46) were important risk factors for active epilepsy. After the second survey, 39 children from the same birth cohort with previously undiagnosed epilepsy were identified, thus the incidence rate of active epilepsy is 187 per 100,000 per year (95% CI: 133-256) in children aged 6-12 years. CONCLUSIONS: There is a considerable burden of epilepsy in older children living in this area of rural Kenya, with a family history of seizures and a history of febrile seizures identified as risk factors for developing epilepsy
Observation of the decay B+ → ψ(2S)ϕ(1020)K+ in pp collisions at s=8TeV
No full textThe decay B+→ψ(2S)ϕ(1020)K+ is observed for the first time using data collected from pp collisions at s=8TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 19.6fb−1. The branching fraction of this decay is measured, using the mode B+→ψ(2S)K+ as normalization, to be (4.0±0.4(stat)±0.6(syst)±0.2(B))×10−6, where the third uncertainty is from the measured branching fraction of the normalization channel. © 2016 The Author(s
Observation of the decay <tex>B^{+}\rightarrow\psi(2S)\phi(1020)K^{+}</tex> = 8 TeV
No full textAbstract: The decay B+ -> psi(2S) phi(1020) K+ is observed for the first time using data collected from pp collisions at root S = 8 TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 19.6 fb(-1). The branching fraction of this decay is measured, using the mode B+ -> psi(2S) K+ as normalization, to be (4.0 +/- 0.4 (stat)+/- 0.6 (syst)+/- 0.2 (B)) x 10(-6), where the third uncertainty is from the measured branching fraction of the normalization channel. (C) 2016 The Author(s). Published by Elsevier B.V
Measurement of the CP-violating phase phi(s) in the B-s(0) -> J/psi phi(1020) -> mu(+)mu-K+K- channel in proton-proton collisions at root s=13 TeV
No full textThe CP-violating weak phase ?s and the decay width difference ??s between the light and heavy B0s mass eigenstates are measured with the CMS detector at the LHC in a sample of 48 500 reconstructed B0s? J/I) d (1020) ?11+11? K+K? events. The measurement is based on a data sample corresponding to an integrated luminosity of 96.4 fb?1, collected in proton-proton collisions at ?s = 13 TeV in 2017?2018. To extract the values of ?s and ??s, a time-dependent and flavor-tagged angular analysis of the 11+11?K+K? final state is performed. The analysis employs a dedicated tagging trigger and a novel opposite-side muon flavor tagger based on machine learning techniques. The measurement yields ?s = ?11 ?50 (stat) ? 10 (syst) mrad and ??s = 0.114 ? 0.014 (stat)? 0.007 (syst) ps?1, in agreement with the standard model predictions. When combined with the previous CMS measurement at ?s = 8 TeV, the following values are obtained: ?s = ?21 ? 44 (stat) ? 10 (syst) mrad, ??s = 0.1032 ? 0.0095 (stat) ? 0.0048 (syst) ps?1, a significant improvement over the 8 TeV result. ? 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY licens
Measurement of the CP-violating phase phi s in the B0s at root s=13 TeV s -> J/psi phi(1020) -> & micro; plus & micro;& minus; K plus K & minus; channel in proton-proton collisions at & nbsp;root s=13 TeV
No full textAbstract: The CP-violating weak phase ?s and the decay width difference ??s between the light and heavy B0s mass eigenstates are measured with the CMS detector at the LHC in a sample of 48 500 reconstructed B0s? J/I) d (1020) ?11+11? K+K? events. The measurement is based on a data sample corresponding to an integrated luminosity of 96.4 fb?1, collected in proton-proton collisions at ?s = 13 TeV in 2017?2018. To extract the values of ?s and ??s, a time-dependent and flavor-tagged angular analysis of the 11+11?K+K? final state is performed. The analysis employs a dedicated tagging trigger and a novel opposite-side muon flavor tagger based on machine learning techniques. The measurement yields ?s = ?11 ?50 (stat) ? 10 (syst) mrad and ??s = 0.114 ? 0.014 (stat)? 0.007 (syst) ps?1, in agreement with the standard model predictions. When combined with the previous CMS measurement at ?s = 8 TeV, the following values are obtained: ?s = ?21 ? 44 (stat) ? 10 (syst) mrad, ??s = 0.1032 ? 0.0095 (stat) ? 0.0048 (syst) ps?1, a significant improvement over the 8 TeV result. ? 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY licens
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