Evidence for synchronous cleavage of N-H and C-C bonds: bis(2,2￠-bipyridyl)copper(II) permanganate oxidation of cobalt(III) bound and unbound α-amino acids

Summary Oxidation of pentaamminecobalt(III) complexes of α-aminoacids by bis(2,2¢-bipyridyl) copper(II) permanganate in 50% HOAc-50% H₂O (v/v) aqueous acetic acid medium. This oxidation as a diagnostic tool to find out the fraction proceeding by synchronous cleavages of N-H and C-C bonds.     

Mass Spectrometry Based Mechanistic Insights into Formation of Tris Conjugates: Implications on Protein Biopharmaceutics

We present here extensive mass spectrometric studies on the formation of a Tris conjugate with a therapeutic monoclonal antibody. The results not only demonstrate the reactive nature of the Tris molecule but also the sequence and reaction conditions that trigger this reactivity. The results corroborate the fact that proteins are, in general, prone to conjugation and/or adduct formation reactions and any modification due to this essentially leads to formation of impurities in a protein sample. Further, the results demonstrate that the conjugation reaction happens via a succinimide intermediate and has sequence specificity. Additionally, the data presented in this study also shows that the Tris formation is produced in-solution and is not an in-source phenomenon. We believe that the facts given here will open further avenues on exploration of Tris as a conjugating agent as well as ensure that the use of Tris or any ionic buffer in the process of producing a biopharmaceutical drug is monitored closely for the presence of such conjugate formation.

Open image in new window

Graphical Abstract ?

     

On degrees of maps between Grassmannians

Let G_n,k denote the oriented grassmann manifold of orientedk-planes in ℝⁿ. It is shown that for any continuous mapf: G_n,k → G_n,k, dim G_n,k = dim G_m,l = l(m −l), the Brouwer’s degree is zero, providedl > 1,n ≠ m. Similar results for continuous mapsg: ℂG_m,l → ℂG_n,k,h: ℍG_m,l → ℍG_n,k, 1 ≤ l < k ≤ n/2, k(n — k) = l(m — l) are also obtained.     

A modified evidential methodology of identifying influential nodes in weighted networks

How to identify influential nodes in complex networks is still an open hot issue. In the existing evidential centrality (EVC), node degree distribution in complex networks is not taken into consideration. In addition, the global structure information has also been neglected. In this paper, a new Evidential Semi-local Centrality (ESC) is proposed by modifying EVC in two aspects. Firstly, the Basic Probability Assignment (BPA) of degree generated by EVC is modified according to the actual degree distribution, rather than just following uniform distribution. BPA is the generation of probability in order to model uncertainty. Secondly, semi-local centrality combined with modified EVC is extended to be applied in weighted networks. Numerical examples are used to illustrate the efficiency of the proposed method.     

Spinodal decomposition in a model colloid-polymer mixture in microgravity

We study phase separation in a deeply quenched colloid-polymer mixture in microgravity on the International Space Station using small-angle light scattering and direct imaging. We observe a clear crossover from early-stage spinodal decomposition to late-stage, interfacial-tension-driven coarsening. Data acquired over 5 orders of magnitude in time show more than 3 orders of magnitude increase in domain size, following nearly the same evolution as that in binary liquid mixtures. The late-stage growth approaches the expected linear growth rate quite slowly.     

A method for stochastic constrained optimization using derivative-free surrogate pattern search and collocation

Recent advances in coupling novel optimization methods to large-scale computing problems have opened the door to tackling a diverse set of physically realistic engineering design problems. A large computational overhead is associated with computing the cost function for most practical problems involving complex physical phenomena. Such problems are also plagued with uncertainties in a diverse set of parameters. We present a novel stochastic derivative-free optimization approach for tackling such problems. Our method extends the previously developed surrogate management framework (SMF) to allow for uncertainties in both simulation parameters and design variables. The stochastic collocation scheme is employed for stochastic variables whereas Kriging based surrogate functions are employed for the cost function. This approach is tested on four numerical optimization problems and is shown to have significant improvement in efficiency over traditional Monte-Carlo schemes. Problems with multiple probabilistic constraints are also discussed.     

Unsteady deflagration speed of an auto-ignitive dimethyl-ether (DME)/air mixture at stratified conditions

The propagation speed of an auto-ignitive dimethyl-ether (DME)/air mixture at elevated pressures and subjected to monochromatic temperature oscillations is numerically evaluated in a one-dimensional statistically stationary configuration using fully resolved numerical simulations with reduced kinetics and transport. Two sets of conditions with temperatures within and slightly above the negative temperature coefficient (NTC) regime are simulated to investigate the fundamental aspects of auto-ignition and flame propagation along with the transition from auto-ignitive deflagration to spontaneous propagation regimes under thermal stratification. Contrary to the standard laminar flame speed, the steady propagation speed of an auto-ignitive front is observed to scale proportionally to its level of upstream reactivity. It is shown that this interdependence is primarily influenced by the characteristic residence time and the homogeneous auto-ignition delay. Furthermore, the unsteady reaction front in either of the two cases responds distinctly to the imposed stratification. Specifically, the results in both cases show that the dynamic flame response depends on the mean temperature at the flame base T_b and the time-scale of thermal stratification. It is also found that, based on T_b and the propensity of the mixture to two-stage chemistry, the instantaneous peak propagation speed and the overall time taken to achieve that speed differs considerably. A displacement speed analysis is carried out to elucidate the underlying combustion modes that are responsible for such a variation in flame response.     

Monitoring redox-sensitive paramagnetic contrast agent by EPRI, OMRI and MRI

A comparative study of tissue redox-status imaging using commonly used redox sensitive nitroxides has been carried out using electron paramagnetic resonance imaging (EPRI), Overhauser magnetic resonance imaging (OMRI) and conventional T(1)-weighted magnetic resonance imaging, MRI. Imaging studies using phantoms of different nitroxides at different concentration levels showed that EPRI and OMRI sensitivities were found to be linearly dependent on line width of nitroxides up to 2 mM, and the enhancement in MRI intensity was linear up to 5 mM. The sensitivity and resolution of EPRI and OMRI images depended significantly on the line width of the nitroxides whereas the MRI images were almost independent of EPR line width. Reduction of the paramagnetic 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3CP) by ascorbic acid (AsA) to the diamagnetic by hydroxylamine was monitored from a sequence of temporal images, acquired using the three imaging modalities. The decay rates determined by all the three modalities were found to be similar. However the results suggest that T(1)-weighted MRI can monitor the redox status, in addition to providing detailed anatomical structure in a short time. Therefore, a combination of MRI with nitroxides as metabolically responsive contrast agents can be a useful technique for the in vivo imaging probing tissue redox status.