Improvement of α-amino Ester Hydrolase Stability via Computational Protein Design.

Amino ester hydrolases (AEHs) are capable of rapid synthesis of cephalexin but suffer from rapid deactivation even at low temperatures. Previous efforts to engineer AEH have generated several improved variants but have been limited in scope in part due to limitations in activity assay throughput for ß-lactam synthesis reactions. Rational design of 'whole variants' was explored to rapidly improve AEH thermostability by mutating between 3-15% of residues. Most variants were found to be inactive due to a mutated calcium binding site, the function of which has not previously been described. Four active variants, all with improved melting temperatures, were characterized in terms of synthesis and hydrolysis activity, melting temperature, and deactivation at 25°C. Two variants were found to have improved total turnover numbers relative to the initial AEH variant; however, a clear tradeoff exists between improved stability and overall activity of each variant.

Quantifying Dense Multicomponent Slurries with In-Line ATR-FTIR and Raman Spectroscopies: A Hanford Case Study.

The multiphase nature of slurries can make them difficult to process and monitor in real time. For example, the nuclear waste slurries present at the Hanford site in Washington State are multicomponent, multiphase, and inhomogeneous. Current analytical techniques for analyzing radioactive waste at Hanford rely on laboratory results from an on-site analytical laboratory, which can delay processing speed and create exposure risks for workers. However, in-line probes can provide an alternative route to collect the necessary composition information. In the present work, Raman spectroscopy and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy are tested on simulants of nuclear waste slurries containing up to 23.2 wt % solids. We observe ATR-FTIR spectroscopy to be effective in measuring the solution phase of the studied slurry systems (3.52% mean percent error), while Raman spectroscopy provides information about the suspended solids in the slurry system (18.21% mean percent error). In-line measurement of multicomponent solids typical of nuclear waste processing has been previously unreported. The composition of both the solution and solid phases is vital in ensuring stable glass formulation and effective disposal of nuclear waste at Hanford. Raman and ATR-FTIR spectroscopies can provide a safer and faster alternative for acquiring compositional information on nuclear waste slurries.

Using the weighted Lorenz curve to represent balance in collaborations: the BIC indicator.

This article aims to add to the body of indicators used to study collaboration in science. We propose a new indicator to measure balance in collaboration (BIC) which is based on the Gini evenness index for a weighted Lorenz curve. The new indicator of balance builds upon and extends the use of, our previously introduced indicator of relative intensity of collaboration (RIC). We present examples based on the collaboration network between the twenty largest countries contributing to science during 2000-2020.

Selectivity and kinetic modeling of penicillin G acylase variants for the synthesis of cephalexin under a broad range of substrate concentrations.

The kinetics of cephalexin synthesis and hydrolysis of the activated acyl-donor precursor phenylglycine methyl ester (PGME) were characterized under a broad range of substrate concentrations. A previously developed model by Youshko-Svedas involving the formation of the acyl-enzyme complex followed by binding of the nucleophilic ß-lactam donor does not fully estimate the maximum reaction yields for cephalexin synthesis at different concentrations using initial-rate data. 7-aminodesacetoxycephalosporanic acid (7-ADCA) was discovered to be a potent inhibitor of cephalexin hydrolysis, which may account for the deviation from model predictions. Three kinetic models were compared for cephalexin synthesis, with the model incorporating competitive inhibition due to 7-ADCA yielding the best fit. Additionally, the ßF24A variant and Assemblase® did not exhibit significantly different kinetics for the synthesis of cephalexin compared to the wild-type, for the concentration range evaluated and for both initial-rate experiments and time-course synthesis experiments. Lastly, a continuous stirred-tank reactor for cephalexin synthesis was simulated using the model incorporating competitive inhibition by 7-ADCA, with clear tradeoffs observed between productivity, fractional yield, and PGME conversion.

Reactor Design and Optimization of α-Amino Ester Hydrolase- Catalyzed Synthesis of Cephalexin.

Pharmaceutical production quality has recently been a focus for improvement through incorporation of end-to-end continuous processing. Enzymatic ß-lactam antibiotic synthesis has been one focus for continuous manufacturing, and α-amino ester hydrolases (AEHs) are currently being explored for use in the synthesis of cephalexin due to their high reactivity and selectivity. In this study, several reactors were simulated to determine how reactor type and configuration impacts reactant conversion, fractional yield toward cephalexin, and volumetric productivity for AEH-catalyzed cephalexin synthesis. The primary reactor configurations studied are single reactors including a continuous stirred-tank reactor (CSTR) and plug flow reactor (PFR) as well as two CSTRS and a CSTR + PFR in series. Substrate concentrations fed to the reactors as well as enzyme concentration in the reactor were varied. The presence of substrate inhibition was found to have a negative impact on all reactor configurations studied. No reactor configuration simultaneously allowed high substrate conversion, high fractional yield, and high productivity; however, a single PFR was found to enable the highest substrate conversion with higher fractional yields than all other reactor configurations, by minimizing substrate inhibition. Finally, to further demonstrate the impact of substrate inhibition, an AEH engineered to improve substrate inhibition was simulated and Pareto optimal fronts for a CSTR catalyzed with the current AEH were compared to Pareto fronts for the improved AEH. Overall, reduced substrate inhibition would allow for high substrate conversion, fractional yield, and productivity with only a single CSTR.

COVID-19, the Yule-Simpson paradox and research evaluation.

The Yule-Simpson paradox refers to the fact that outcomes of comparisons between groups are reversed when groups are combined. Using Essential Sciences Indicators, a part of InCites (Clarivate), data for countries, it is shown that although the Yule-Simpson phenomenon in citation analysis and research evaluation is not common, it isn't extremely rare either. The Yule-Simpson paradox is a phenomenon one should be aware of, otherwise one may encounter unforeseen surprises in scientometric studies.

An Autobiography of Ronald W. Rousseau.

This article provides a synopsis of my professional career, from the decision to study chemical engineering to leadership of one of the top academic programs in that field. I describe how I chose to devote my research to phenomena associated with crystallization as practiced for separation and purification and then made the transition to leader of an academic program. Embedded in the coverage are descriptions of research advances coming from exploration of secondary nucleation, especially how collisions of crystals in supersaturated environments dominate the behavior of industrially relevant crystallization processes. I recount some of the challenges associated with becoming a school chair and how the program I led grew. The story illuminates the contributions of my many mentors, colleagues, and students.

A warning for Chinese academic evaluation systems: short-term bibliometric measures misjudge the value of pioneering contributions.

Publication citation-based research evaluation, even if only in support of peer review, is not everywhere, on every level, or for everyone suitable, because of differences in scientific research, patterns of research output, stages of scientific evolution, and merits-scientific or societal-of scientific results.

Science deserves to be judged by its contents, not by its wrapping: Revisiting Seglen's work on journal impact and research evaluation.

The scientific foundation for the criticism on the use of the Journal Impact Factor (JIF) in evaluations of individual researchers and their publications was laid between 1989 and 1997 in a series of articles by Per O. Seglen. His basic work has since influenced initiatives such as the San Francisco Declaration on Research Assessment (DORA), the Leiden Manifesto for research metrics, and The Metric Tide review on the role of metrics in research assessment and management. Seglen studied the publications of only 16 senior biomedical scientists. We investigate whether Seglen's main findings still hold when using the same methods for a much larger group of Norwegian biomedical scientists with more than 18,000 publications. Our results support and add new insights to Seglen's basic work.

From a word to a world: the current situation in the interdisciplinary field of synthetic biology.

Using a carefully designed search query, we describe the field of synthetic biology in terms of leading countries, organizations and funding sources. Besides articles we also paid some attention to patents. The USA is the leading country in this field, followed by China. There is a clear exponential growth in the field of synthetic biology over the latest 14 years. Keywords were analyzed using the notion of year-based h-indices, core gap and relative core gap. We conclude that the term "synthetic biology" hides a large world ready to be explored by interdisciplinary research.

Pretreatment of Hanford medium-curie wastes by fractional crystallization.

Acceleration of the schedule for decontamination of the Hanford site using bulk vitrification requires implementation of a pretreatment operation. Medium-curie waste must be separated into two fractions: one is to go to a waste treatment and immobilization plant and a second, which is low-activity waste, is to be processed by bulk vitrification. The work described here reports research on using fractional crystallization for that pretreatment. Sodium salts are crystallized by evaporation of water from solutions simulating those removed from single-shell tanks, while leaving cesium in solution. The crystalline products are then recovered and qualified as low-activity waste, which is suitable upon redissolution for processing by bulk vitrification. The experimental program used semibatch operation in which a feed solution was continuously added to maintain a constant level in the crystallizer while evaporating water. The slurry recovered at the end of a run was filtered to recover product crystals, which were then analyzed to determine their composition. The results demonstrated that targets on cesium separation from the solids, fractional recovery of sodium salts, and sulfate content of the recovered salts can be achieved by the process tested.

On indexing in the Web of Science and predicting journal impact factor.

We discuss what document types account for the calculation of the journal impact factor (JIF) as published in the Journal Citation Reports (JCR). Based on a brief review of articles discussing how to predict JIFs and taking data differences between the Web of Science (WoS) and the JCR into account, we make our own predictions. Using data by cited-reference searching for Thomson Scientific's WoS, we predict 2007 impact factors (IFs) for several journals, such as Nature, Science, Learned Publishing and some Library and Information Sciences journals. Based on our colleagues' experiences we expect our predictions to be lower bounds for the official journal impact factors. We explain why it is useful to derive one's own journal impact factor.

Solubility and prediction of the heat of solution of sodium naproxen in aqueous solutions.

The solubility of sodium naproxen was determined over a range of temperatures from 15.2 degrees C to 39.7 degrees C by two methods: analyses of samples from equilibrated solutions and a recently developed procedure utilizing a focused-beam reflectance method (FBRM). The results demonstrate the utility of the newer and, in some cases, simpler method. A discontinuity in the solubility was observed at 29.8 degrees C, identifying the temperature as which the dihydrate and anhydrous forms of sodium naproxen trade places as being the more stable of the two forms. The heats of solution for the two pseudopolymorphs were obtained from van't Hoff plots of the solubility data. These results were used to demonstrate how the heat of solution of one form can be estimated using the heat of dehydration obtained from differential scanning calorimetry (DSC) and the heat of solution from another form.

Indicadores bibliométricos y econométricos en la evaluación de instituciones científicas

Este artículo consta de 2 partes. La primera describe la evaluación de una pequeña universidad a partir de datos cienciométricos, con el objetivo principal de analizar la investigación con visibilidad internacional. La segunda parte muestra cómo un método econométrico (DEA: data enveloping analysis) puede aplicarse entre otros aspectos como medio de evaluación para determinar los recursos disponibles. Asimismo se demuestra cómo un cuerpo teórico que combina la bibliometría, la cienciometría y la econometría puede aplicarse a problemas concretos.

This article consists of two parts: the first part describes the evaluation of a small university it is based on scientometric data and aims mainly at the evaluation of internationally visible research. The second part shows how an econometric method (DEA: data enveloping analysis) can be used to include teaching and other aspects, e.g. fund raising, into the evaluation. Both approaches show how a body of bibliometric, scientometric and econometric theory can be applied to real world problems.