Some topics in the kinetics of protein aggregation

Preliminary results are presented for the kinetics of phase separation in three distinct models of protein aggregation. The first is a model of the formation of spherical microcrystals of insulin via an initial formation of fractal clusters of insulin. The results of our Brownian dynamics study of this model are in qualitative agreement with a recent experimental study (Biophys. Jour. 89 (2005) 3424-3433) of microcrystal formation from aqueous mixtures of insulin. A second work involves a theory for the formation of metastable bundles of sickle hemoglobin from fibers, based on a recent generic theory of bundle formation (Phy. Rev. Lett. 99 (2007) 098101). We also discuss a model for the microscopic formation of these fibers. Finally, we discuss preliminary results for the kinetics of cluster formation for a six patch model of protein crystallization

Treatment outcomes of various types of tuberculosis in Pakistan, 2006 and 2007

Measuring treatment outcome is important for successful tuberculosis (TB) control programmes. The purpose of this study was to examine the outcomes of various types of TB cases registered in Pakistan over a 2-year period and compare those outcomes among the different provinces and regions of the country. A retrospective, cohort study was conducted in which TB treatment outcome reports were reviewed. Of the 349 694 pulmonary TB cases registered in Pakistan during 2006 and 2007, 309 154 (88.4%) were treated successfully. Treatment success was significantly higher in new smear-positive cases and lower in retreatment cases. Among the provinces and regions, treatment success was significantly higher in 4 out of 8 provinces. Treatment success needs to be improved, particularly in retreatment cases. The national TB control programme should review the provincial and regional programmes and learn lessons from well-performing programmes. Patient factors that may affect the treatment outcome should be also studied

Analysis of Crocetins and Safranal variations in Saffron (Crocus sativus) Stigma Samples and Dietary Supplements using HPLC/UHPLC-PDA-MS: Chemical Profiling and Chemometric Analysis using LC-QToF

Saffron, the most expensive spice in the world, is comprised of dried and dark red stigma of Crocus sativus L. flowers of the Iridaceae family. It is mainly used as a spice for imparting color, fragrance, and flavor to food, but its medicinal and dyeing properties are also well known. In the United States, saffron products are used as dietary supplements for mood elevation, relaxation, weight loss, and to increase metabolism. This paper describes two analytical methods for the determination of crocetin esters, picrocrocin, and safranal in saffron samples and dietary supplements for inclusion in a monograph under development by the American Herbal Pharmacopoeia. Method validation showed satisfactory results in linearity, precision and recovery. The content of picrocrocin, safranal and crocetin esters ranged from 0.6-10.2%, 0.02-0.22%, and 2.8- 25.6%, respectively for thirty-seven stigma samples. Twenty-nine dietary supplements were analyzed. No saffron compounds were found in 16 (55%) of these products. Flower of Carthamus tinctorius and fruit of Gardenia jasminoides were the main adulterants detected in dietary supplements. Summarily, 60 compounds, including five standards were tentatively identified from saffron stigma, style, and petal samples using high resolution mass spectrometry. Principle component analysis was used to discriminate between saffron stigma samples and dietary supplements. The results indicated that commercial products are of variable quality and that this analytical method is suitable for quality assessment of a variety of both raw material and finished dietary supplements.https://egrove.olemiss.edu/pharm_annual_posters_2024/1015/thumbnail.jp

Space of State Vectors in PT Symmetrical Quantum Mechanics

Space of states of PT symmetrical quantum mechanics is examined. Requirement that eigenstates with different eigenvalues must be orthogonal leads to the conclusion that eigenfunctions belong to the space with an indefinite metric. The self consistent expressions for the probability amplitude and average value of operator are suggested. Further specification of space of state vectors yield the superselection rule, redefining notion of the superposition principle. The expression for the probability current density, satisfying equation of continuity and vanishing for the bound state, is proposed.Comment: Revised version, explicit expressions for average values and probability amplitude adde

Spots structure and stratification of helium and silicon in the atmosphere of He-weak star HD 21699

The magnetic star HD 21699 possesses a unique magnetic field structure where the magnetic dipole is displaced from the centre by 0.4 +/- 0.1 of the stellar radius (perpendicularly to the magnetic axis), as a result, the magnetic poles are situated close to one another on the stellar surface with an angular separation of 55$^o$ and not 180$^o$ as seen in the case of a centred dipole. Respectively, the two magnetic poles form a large "magnetic spot". High-resolution spectra were obtained allowing He I and Si II abundance variations to be studied as a function of rotational phase. The results show that the helium abundance is concentrated in one hemisphere of the star, near the magnetic poles and it is comparatively weaker in another hemisphere, where magnetic field lines are horizontal with respect to the stellar surface. At the same time, the silicon abundance is greatest between longitudes of 180 - 320$^o$, the same place where the helium abundance is the weakest. These abundance variations (with rotational phase) support predictions made by the theory of atomic diffusion in the presence of a magnetic field. Simultaneously, these result support the possibility of the formation of unusual structures in stellar magnetic fields. Analysis of vertical stratification of the silicon and helium abundances shows that the boundaries of an abundance jump (in the two step model) are similar for each element; $\tau_{5000}$ = 0.8-1.2 for helium and 0.5-1.3 for silicon. The elemental abundances in the layers of effective formation of selected absorption lines for various phases are also correlated with the excitation energies of low transition levels: abundances are enhanced for higher excitation energy and higher optical depth within the applied model atmosphere.Comment: accepted by MN, 7 pagers, 10 figs, 3 table

Glycosylation characterization of therapeutic mAbs by top- and middle-down mass spectrometry

A reference monoclonal antibody IgG1 and a fusion IgG protein were analyzed by top- and middle-down mass spectrometry with multiple fragmentation techniques including electron transfer dissociation (ETD) and matrix-assisted laser desorption ionization in-source decay (MALDI-ISD) to investigate heterogeneity of glycosylated protein species. Specifically, glycan structure, sites, relative abundance levels, and termini structural conformation were investigated by use of Fourier transform ion cyclotron resonance (FT-ICR) or high performance liquid chromatography electrospray ionization (HPLC-ESI) linked to an Orbitrap. Incorporating a limited enzymatic digestion by immunoglobulin G-degrading enzyme Streptococcus pyogenes (IdeS) with MALDI-ISD analysis extended sequence coverage of the internal region of the proteins without pre-fractionation. The data in this article is associated with the research article published in Journal of Proteomics (Tran et al., 2015)

Utility of the CHA2DS2-VASc score for predicting ischaemic stroke in patients with or without atrial fibrillation: a systematic review and meta-analysis

AIMS: Anticoagulants are the mainstay treatment for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), and the CHA2DS2-VASc score is widely used to guide anticoagulation therapy in this cohort. However, utility of CHA2DS2-VASc in NVAF patients is debated, primarily because it is a vascular scoring system, which does not incorporate atrial fibrillation related parameters. Therefore, we conducted a meta-analysis to estimate the discrimination ability of CHA2DS2-VASc in predicting ischaemic stroke overall, and in subgroups of patients with or without NVAF. METHODS AND RESULTS: PubMed and Embase databases were searched till June 2020 for published articles that assessed the discrimination ability of CHA2DS2-VASc, as measured by C-statistics, during mid-term (2-5 years) and long-term (\u3e5 years) follow-up. Summary estimates were reported as random effects C-statistics with 95% confidence intervals (CIs). Seventeen articles were included in the analysis. Nine studies (n = 453 747 patients) reported the discrimination ability of CHA2DS2-VASc in NVAF patients, and 10 studies (n = 138 262 patients) in patients without NVAF. During mid-term follow-up, CHA2DS2-VASc predicted stroke with modest discrimination in the overall cohort [0.67 (0.65-0.69)], with similar discrimination ability in patients with NVAF [0.65 (0.63-0.68)] and in those without NVAF [0.69 (0.68-0.71)] (P-interaction = 0.08). Similarly, at long-term follow-up, CHA2DS2-VASc had modest discrimination [0.66 (0.63-0.69)], which was consistent among patients with NVAF [0.63 (0.54-0.71)] and those without NVAF [0.67 (0.64-0.70)] (P-interaction = 0.39). CONCLUSION: This meta-analysis suggests that the discrimination power of the CHA2DS2-VASc score in predicting ischaemic stroke is modest, and is similar in the presence or absence of NVAF. More accurate stroke prediction models are thus needed for the NVAF population