Characterization of dihydrostreptomycin‐related substances by liquid chromatography coupled to ion trap mass spectrometry

Dihydrostreptomycin sulphate (DHS) is a water‐soluble, broad‐spectrum aminoglycoside antibiotic. For quantitative analysis, the European Pharmacopoeia (Ph. Eur.) prescribes an ion‐pairing liquid chromatography/ultraviolet (LC/UV) method using a C18 stationary phase. Several unknown compounds were detected in commercial samples. Hence, for characterization of these unknown peaks in a commercial DHS sample, the Ph. Eur. method was coupled to mass spectrometry (MS). However, since the Ph. Eur. method uses a non‐volatile mobile phase, each peak eluted was collected and desalted before introduction into the mass spectrometer. The desalting procedure was applied to remove the non volatile salt, buffer and ion‐pairing reagent in the collected fraction. In total, 20 impurities were studied and 14 of them were newly characterized. Five impurities which are already reported in the literature were also traced in this LC/UV method. Copyright © 2009 John Wiley & Sons, Ltd.     

Versatile and controlled synthesis of resorbable star‐shaped polymers using a spirocyclic tin initiator—Reaction optimization and kinetics

A spirocyclic tin initiator was synthesized from pentaerythritol ethoxylate and dibutyltin oxide and used to polymerize L ‐lactide with dichloromethane, chloroform, toluene, and chlorobenzene as solvents. The reactions were performed at different temperatures and it is concluded that neither the temperature nor the solvent affects the molecular weight or the molecular weight distribution of the star‐shaped polymers. The reaction rate was significantly increased by raising the reaction temperature or choosing a solvent with a low dielectric constant. All polymers showed a molecular‐weight distribution below 1.19 and a molecular‐weight determined by the initial monomer to initiator concentration ([M]₀/[I]). No induction period was seen for the polymerizations. They were all first order in initiator and the degree of aggregation in toluene at 110 °C was found to be 4/5. The glass transition temperature and the melting temperature of the star‐shaped polymers increase with increasing arm length. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 596–605, 2006     

Diagnostic Robust Generalized Potential Based on Index Set Equality (DRGP (ISE)) for the identification of high leverage points in linear model

High leverage points have tremendous effect in linear regression analysis. When a group of high leverage points is present in a dataset, the existing detection methods fail to detect them correctly. This problem is due to the masking and swamping effects. We propose the Diagnostic Robust Generalized Potentials Based on Index Set Equality (DRGP(ISE)) in this regard. The DRGP(ISE) takes off from the Diagnostic Robust Generalized Potential Based on Minimum Volume Ellipsoid (DRGP(MVE)). However, the running time of ISE is much faster than MVE. Monte Carlo simulation study and numerical data indicate that DRGP(ISE) works excellently to detect the actual high leverage points and reduce masking and swamping effects in a linear model.     

7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir

Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5 h in sequential flow operations from commercially available materials. Key features of the synthesis include rapid manufacturing time for pyridone formation, one‐step direct amidation of a functionalized pyridone, and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput.     

Unit Interval Orders of Open and Closed Intervals

A poset P = (X, ?) is a unit OC interval order if there exists a representation that assigns an open or closed real interval I(x) of unit length to each x ∈ P so that x ? y in P precisely when each point of I (x) is less than each point in I (y). In this paper we give a forbidden poset characterization of the class of unit OC interval orders and an efficient algorithm for recognizing the class. The algorithm takes a poset P as input and either produces a representation or returns a forbidden poset induced in P.     

Absorption time of the Moran process

The Moran process models the spread of mutations in populations on graphs. We investigate the absorption time of the process, which is the time taken for a mutation introduced at a randomly chosen vertex to either spread to the whole population, or to become extinct. It is known that the expected absorption time for an advantageous mutation is on an n‐vertex undirected graph, which allows the behaviour of the process on undirected graphs to be analysed using the Markov chain Monte Carlo method. We show that this does not extend to directed graphs by exhibiting an infinite family of directed graphs for which the expected absorption time is exponential in the number of vertices. However, for regular directed graphs, we show that the expected absorption time is and . We exhibit families of graphs matching these bounds and give improved bounds for other families of graphs, based on isoperimetric number. Our results are obtained via stochastic dominations which we demonstrate by establishing a coupling in a related continuous‐time model. The coupling also implies several natural domination results regarding the fixation probability of the original (discrete‐time) process, resolving a conjecture of Shakarian, Roos and Johnson. © 2016 Wiley Periodicals, Inc. Random Struct. Alg., 49, 137–159, 2016     

Elementary Teachers: Concerns About Implementing a Science Program

The purpose of this study was to examine elementary teachers’ science teaching concerns after participating in a two‐year extensive and sustained science professional development intervention. The intervention consisted of two types of teacher professional development across two years including: (a) summer institutes (60 hours across two years) which provided training on curriculum units, inquiry‐based instructional strategies, problem‐based learning, classroom management, and technology use in the classroom; and (b) coaching (60 hours across two years) which provided teachers support in establishing an investigative classroom and assistance in the implementation of inquiry/problem‐based science units. Teacher data were collected across four different time points: prior to the intervention, after one year of intervention, after two years of intervention, and one year after completion of the intervention. Results from quantitative data supported with qualitative interviews indicated concerns among teachers changed but they were not eliminated. The findings of this study provide evidence that teachers’ concerns may not be eliminated, but with extensive support––concerns become less focused on self and more focused on students.