Rapid analysis of titer,aggregate, and intact mass of antibody therapeutics using automated multi-dimensional liquid chromatography coupled with native mass spectroscopy

Monoclonal antibodies are tetrameric complex proteins, primarily produced using mammalian cell culture. Attributes such as titer, aggregates, and intact mass analysis are monitored during process development/optimization. In the present study, a novel workflow such that the Protein-A affinity chromatography is performed in the first dimension for purification and titer estimation, whereas size exclusion chromatography is employed in the second dimension to characterize size variants using native mass spectrometry. The present workflow offers a significant advantage over the traditionally used standalone Protein-A affinity chromatography followed by size exclusion chromatography analysis in that it can monitor these four attributes in 8 min while requiring a minimal sample size (10–15 μg) and not requiring any manual peak collection. In contrast, the traditional standalone approach requires manual collection of eluted peaks in Protein-A affinity chromatography followed by buffer exchange to a mass-compatible buffer, which can take up to 2–3 h with considerable risk of sample loss, degradation, and induced modifications. As the biopharma industry moves to make analytical testing efficient, we believe that the approach proposed here would be of significant interest due to its ability to monitor multiple process and product quality attributes in a single workflow and via rapid analysis.     

Sorption of anti-infective organic molecules from aqueous solutions onto zirconium phosphate

Amorphous zirconium phosphate (ZP), an inorganic ion exchange material of tetravalent metal acid (tma) salt, is synthesized by the sol-gel method and characterized by elemental analysis (ICP-AES), thermal analysis (TGA, DSC), FT-IR and X-ray diffraction studies. The resistivity of the material to acids, bases and organic solvents is assessed. The sorption behavior of the dyes acriflavin (AF) and brilliant green (BG) toward ZP was studied at 313, 323 and 333 K and the kinetic and thermodynamic parameters evaluated. Adsorption isotherms [Langmuir and Fruendlich], breakthrough capacity and elution behavior of these dyes are also studied. The sorption affinity of dyes towards ZP is BG > AF.     

Binding Interactions in Copper,Silver and Gold π-Complexes

The copper(I), silver(I), and gold(I) metals bind π-ligands by σ-bonding and π-back bonding interactions. These interactions were investigated using bidentate ancillary ligands with electron donating and withdrawing substituents. The π-ligands span from ethylene to larger terminal and internal alkenes and alkynes. Results of X-ray crystallography, NMR, and IR spectroscopy and gas phase experiments show that the binding energies increase in the order Ag<Cu<Au and the binding energies are slightly higher for alkynes than for alkenes. Modulation of the electron density at the metal using substituents on the ancillary ligands shows that the π-back bonding interaction plays a dominant role for the binding in the copper and gold complexes.     

Pressure-induced phase transition and electronic properties of AlN nanowires: an ab initio study

The structural stability of AlN nanowires have been analyzed in wurtzite (B4), zincblende (B3), rocksalt (B1) and CsCl (B2) type phases using density functional theory based ab initio approach. The total energy calculations have been performed in a self-consistent manner using local density approximation as exchange correlation functional. The analysis finds the B4 type phase as most stable amongst the other phases taken into consideration and observes the structural phase transition from B4?→?B3, B4?→?B1, B4?→?B2, B3?→?B1 and B3?→?B2 at 42.7, 76.54, 142, 30.4 and 108.9?GPa respectively. Lattice parameter, bulk modulus and pressure derivatives of AlN nanowires have also been calculated for all the stable phases. The electronic band structure analysis of AlN nanowires shows a semiconducting nature in its B4, B3 and B1 type phases, whereas the B2 type phase is found to be metallic.     

Theoretical investigation of high-pressure phase transitions in Mg1-xSrxO

The stability of Mg_1-xSr_xO solid solution has been analyzed using charge transfer interaction potential (CTIP) model as well as density functional theory-based ab initio approach with Perdew–Burke–Ernzerhof (PBE) type parameterized generalized gradient approximation. The present CTIP model consists of long-range part as modified coulomb interactions and charge transfer forces whereas short-range part includes the van der Waals as well as Hafemeister Flygare type overlap repulsive interactions effective up to next nearest neighbor ions. The present study finds that under the influence of pressure host binary oxides as well as their solid solutions undergo B1→B2 structural phase transition in the pressure range of 54–495 GPa. The variation of ground state properties and transition pressures have also been analyzed as a function of Sr composition. The observed results for the end point members are in agreement to their experimental counterparts and the deviations have been discussed in terms of interactions taken into consideration in two approaches.     

Luminescence study of cerium-doped La2Hf2O7: Effects due to trivalent and tetravalent cerium and oxygen vacancies

X-ray excited emission spectra, photoluminescence excitation and emission spectra, optical reflectivity spectra, and pulsed X-ray and optical excited luminescence decay measurements are reported for cerium-doped La₂Hf₂O₇ powders prepared by solid state synthesis. A broad luminescence associated with oxygen vacancies is observed in the region 350–750 nm with a peak around 460 nm. The photoluminescence spectra and the number of oxygen vacancies vary for samples annealed in oxidizing or reducing atmospheres and with the temperature of the synthesis process. Increasing the cerium concentration reduces the oxygen-vacancy-related emission due to the presence of Ce⁴⁺. First principles calculations predict that Ce⁴⁺ can substitute in Hf sites; this is confirmed from the optical reflectivity spectrum of cerium-doped La₂Hf₂O₇. Photoluminescence excitation and emission spectra characteristic of Ce⁴⁺ charge transfer transitions and possibly Ce³⁺ are also observed. Although trivalent cerium may be present, no emission observed from cerium-doped La₂Hf₂O₇ can be attributed to Ce³⁺ in La sites.     

Investigation of phase segregation in Zn1−xMgxO systems

The present work reports on the synthesis of the Zn_1?xMg_xO (x = 0, 0.02, 0.05, 0.10, 0.15 and 0.20) samples by sol–gel method and the investigations on their structural, morphological and optical properties. X-ray diffraction (XRD) data analysis confirms the formation of pure ZnO phase below 10% Mg doping and MgO related phases appears in 10% doped sample indicating that phase segregation of MgO starts at x ≥ 0.10 samples. The phase segregation observed through XRD analysis is also supported by results from Scanning Electron Microscopy (SEM), Raman spectroscopy and photoluminescence studies. Furthermore, the enhancement in optical band gap, with Mg doping, from 3.1 ± 0.1 eV to 3.5 ± 0.1 eV has been observed through UV–Vis spectroscopic analysis. Above results have been discussed on the basis of defects level observed through Raman and photoluminscence studies.     

On the optimal control of arrivals to a single queue with arbitrary feedback delay

We consider a problem of admission control to a single queue in discrete time. The controller has access to k step old queue lengths only, where k can be arbitrary. The problem is motivated, in particular, by recent advances in high-speed networking where information delays have become prominent. We formulate the problem in the framework of Completely Observable Controlled Markov Chains, in terms of a multi-dimensional state variable. Exploiting the structure of the problem, we show that under appropriate conditions, the multi-dimensional Dynamic Programming Equation (DPE) can be reduced to a unidimensional one. We then provide simple computable upper and lower bounds to the optimal value function corresponding to the reduced unidimensional DPE. These upper and lower bounds, along with a certain relationship among the parameters of the problem, enable us to deduce partially the structural features of the optimal policy. Our approach enables us to recover simply, in part, the recent results of Altman and Stidham, who have shown that a multiple-threshold-type policy is optimal for this problem. Further, under the same relationship among the parameters of the problem, we provide easily computable upper bounds to the multiple thresholds and show the existence of simple relationships among these upper bounds. These relationships allow us to gain very useful insights into the nature of the optimal policy. In particular, the insights obtained are of great importance for the problem of actually computing an optimal policy because they reduce the search space enormously. This revised version was published online in June 2006 with corrections to the Cover Date.