Protease Catalyzed In Situ C-Terminal Modification of Oligoglutamate

One-pot biotransformations gave oligo(γ-l-Et-Glu) decorated with selected amine-functionalized end-groups at C-termini. Motivations for this work were to (i) control the end group structure of peptides synthesized by protease-catalyzed peptide synthesis and (ii) incorporate end-groups that can be used directly or after further modification as polymerizable entities. Papain, bromelain, α-chymotrypsin, Multifect P-3000, and Purafect prime 4000 L were used as catalysts for oligomerization of γ-l-(Et)2-Glu in the presence of monofunctional amines. The series of amine nucleophiles (NH2-R, acyl acceptors) studied mimic phenylalanine in that they possess aromatic rings linked to amine groups by one or more methylenes. Generally, addition of increased quantities of NH2-R from 0 to 30, 50, and 70 mol % with respect to γ-l-(Et)2-Glu results in decreased % yield, but increased mol % of NH2-R end-capped oligo(γ-l-Et-Glu)-NH-R (determined by NMR). Irrespective of the protease used, 2-thiophene methyl amine (TPMA) gave the highest fraction of oligo(γ-l-Et-Glu)-NH-R chains. For example, using Multifect P-3000 and a feed ratio of TPMA-to γ-l-(Et)2-Glu of 7:3, >90 mol % of oligopeptides formed had TPMA C-terminal groups. With all five proteases studied herein, l-phenylalanine and l-histidine did not produce end-capped oligo(γ-l-Et-Glu). In contrast, l-phenylalanine analogs benzylamine (BzA) and l-phenylalaninol (F-OH), both of which lack the α-carboxyl group, gave substantial quantities of oligo(γ-l-Et-Glu)-F-OH or -BzA chains. Hence, the results of this study prove that the promiscuity of proteases used herein can be exploited to create a diverse family of desired end-functionalized oligopeptides. MALDI-TOF spectra recorded of oligo(γ-l-Et-Glu) with amine nucleophiles showed molecular ions that affirmed the formation of corresponding NH2-R functionalized oligo(γ-l-Et-Glu)

Process Simulation of Sulfuric Acid Recovery by Azeotropic Distillation: Vapor–Liquid Equilibria and Thermodynamic Modeling

For development of the new process for the recovery of dilute sulfuric acid by azeotropic distillation proposed in our earlier publication [Li et al., <i>Ind. Eng. Chem. Res.</i>, <b>2013</b>, <i>52</i>, 3481–3489], in this paper, the vapor–liquid equilibria (VLE) for the FeSO₄ + H₂O and H₂SO₄ + FeSO₄ + H₂O systems were first determined by the quasi-static ebulliometric method. The azeotropic temperatures of the H₂SO₄ + H₂O + entrainer (cyclohexane and octane) systems were also measured. The corresponding electrolyte nonrandom two-liquid interaction parameters were obtained by regressing the experimental data with a maximum average absolute deviation of boiling points of 0.83 K. The model with newly obtained parameters was verified by comparing its prediction with the experimental azeotropic temperature for the H₂SO₄ + FeSO₄ + H₂O + C₆H₁₂ quaternary system. The temperature and sulfuric acid concentration ranges of the study were 305.9–396.9 K and 0–86.1 wt %, respectively. Following from the experimental results, semicontinuous distillation experiments for the sulfuric acid recovery were performed with cyclohexane as the entrainer. Equipped with the new parameters, Aspen Plus was adopted to carry out the process simulation for the recovery of dilute sulfuric acid by azeotropic distillation. The simulation results show that when cyclohexane was employed as the entrainer, the dilute sulfuric acid can be concentrated to 68% by a packed column containing 4 theoretical stages and with a reboiler temperature of only 361 K

Protease-Catalyzed Oligomerization of Hydrophobic Amino Acid Ethyl Esters in Homogeneous Reaction Media Using l-Phenylalanine as a Model System

Enzymatic synthesis of oligopeptides from l-phenylalanine ethyl ester hydrochloride (l-Phe-Et·HCl) and other l-form hydrophobic amino acid ester hydrochlorides in water miscible organic cosolvents was studied. Different proteases, water miscible cosolvents, and effect of different ratios of water miscible cosolvents for protease-catalyzed oligo-phenylalanine [oligo(l-Phe)] were compared. The importance of the use of water miscible cosolvents in transforming reactions from heterogeneous to homogeneous conditions as a potent medium engineering tool for protease-catalyzed oligopeptide synthesis is highlighted. For example, at 0.125 M l-Phe-Et·HCl, 20% (v/v) methanol, 18.6 mg/mL bromelain, in phosphate buffer (0.25M, pH 8), 40 °C, for 3 h, oligo(l-Phe) precipitated from the solution to yield 45 ± 5%, in contrast, in the absence of cosolvent oligo(l-Phe) yield of 29 ± 5% was obtained. The following reaction conditions were optimized for bromelain catalyzed oligo(l-Phe) synthesis: pH, temperature, substrate, enzyme, and cosolvent concentrations. DPavg and chain length distribution in the product peptides were investigated by 1H NMR and MALDI-TOF

Multilayer Graphene Terahertz Plasmonic Structures for Enhanced Frequency Tuning Range

Graphene plasmonics has recently found a variety of applications in terahertz photonic devices. High spatial confinement and large frequency tunability are two key advantages of graphene plasmonics. Nevertheless, the frequency tuning range of plasmonic devices employing single-layer graphene is ultimately limited by its carrier density tuning range. Here, we demonstrate that the frequency tuning range of graphene-based plasmonic devices can be further extended by employing multilayer graphene structures. Both our experimental investigations and theoretical calculations show that the frequency tuning range of gate-controlled graphene plasmonic resonators can be significantly enhanced by employing two or three layers of stacked graphene, which is a result of the carrier distributions in multiple layers leading to higher total optical conductivity. However, contrary to the previous prediction, stacking even more graphene layers yields little additional benefit, as the interlayer charge screening effect leads to insignificant gate-induced carrier density in additional graphene layers. Our findings provide new insights for designing and optimizing graphene-based plasmonic structures for various photonic device applications, such as modulators, sensors, and detectors

Machine Learning-Aided Design of Materials with Target Elastic Properties

A set of universal descriptors which combines atomic properties with crystal fingerprint are presented to build interpretable models for elastic property prediction. Using the well-performed model, 100 materials with large predicted elastic moduli are screened out and then validated by the first-principles calculations. When performing projection analysis, we find that compounds with large and small elastic moduli are clearly divided into two parts by the average value of volume and atomization enthalpy (ΔHatomic), and the relation between them is given by two discriminant equations, suggesting that compounds composed of elements with large ΔHatomic are potential large elastic moduli materials. Following this rule, we design several new stable materials like ReTcB4 and ReB which have high elastic moduli. This method is valuable for high-throughput screening and material design

Tunable Conductivity and Half Metallic Ferromagnetism in Monolayer Platinum Diselenide: A First-Principles Study

On basis of the first-principles calculations, we have studied the effects of hole doping and biaxial tensile strain on the electronic and magnetic properties of monolayer of platinum diselenide (PtSe2). Due to the large density of states near the valence band edge, this nonmagnetic monolayer semiconductor switches to a ferromagnetic half metal within a small range of hole doping. With an increase of hole density, average magnetic moment per carrier also increases and reaches at its maximum value over a specific range of carrier density, while the system remains in a half metal state before the magnetic moment abruptly begins to fall. We also predict a critical value of biaxial tensile strain (5%) for doped monolayer PtSe2, after which the optimal carrier density becomes constant, while the magnetic moment/carrier gradually increases and the ferromagnetic state of the system becomes more stable with increasing values of strain. This work paves a possible way to engineer the magnetic properties of the two-dimensional nanomaterials

Table2_Developing a Core Outcome Set for Clinical Trials of Chinese Medicine for Hyperlipidemia.docx

Background: Chinese medicine (CM) is widely used for treating hyperlipidemias, especially in China. However, the heterogeneity of outcomes measured and reported across trials exacerbates the obstacles of evidence synthesis and effectiveness comparison. In this study, we develop a core outcome set (COS) for CM clinical trials for hyperlipidemia (COS-CM-Hyperlipidemia) to tackle the outcome issues.Methods: We generated candidate outcomes through a systematic review of interventional and observational studies of Chinese medicine for hyperlipidemias. The comprehensive search strategy was employed. Study selection and data collection were independently done by two researchers. We searched clinical trial registry platform to supplement the outcomes list extracted by systematic review. Then, we conducted a three-round Delphi survey. The stakeholders were hyperlipidemia patients, clinicians or researchers, in either CM/integrated Chinese or Western medicine, clinical pharmacy, clinical epidemiology or statisticians, or editors of important relevant journals and an ethicist. They used a 9-point Likert scale to determine how important they felt each outcome was in determining treatment success. A consensus meeting was held to confirm the final COS, based on the Delphi survey results.Results: We identified a total of 433 outcomes from 3,547 articles, and 28 outcomes from 367 registered trials. After standardization, we selected 71 outcomes to develop a preliminary outcome list for further consensus. After three Delphi survey rounds and one consensus meeting, the most important outcomes were determined for COS-CM-Hyperlipidemia. It included cardiovascular events, low-density lipoprotein cholesterol, risk of cardiovascular disease, total cholesterol, carotid intima-media thickness, high-density lipoprotein cholesterol, triglycerides, cerebrovascular events, adverse drug reactions and patient-reported symptoms.Conclusion: COS-CM-Hyperlipidemia may improve outcome reporting consistency in clinical trials. Further work is needed to explore the optimal methods for measuring these outcomes.Registration: The Core Outcome Measures in Effectiveness Trials Initiative (COMET): http://www.cometinitiative.org/studies/details/983. Registered on 25 April 2017.</p

Table1_Developing a Core Outcome Set for Clinical Trials of Chinese Medicine for Hyperlipidemia.DOCX

Background: Chinese medicine (CM) is widely used for treating hyperlipidemias, especially in China. However, the heterogeneity of outcomes measured and reported across trials exacerbates the obstacles of evidence synthesis and effectiveness comparison. In this study, we develop a core outcome set (COS) for CM clinical trials for hyperlipidemia (COS-CM-Hyperlipidemia) to tackle the outcome issues.Methods: We generated candidate outcomes through a systematic review of interventional and observational studies of Chinese medicine for hyperlipidemias. The comprehensive search strategy was employed. Study selection and data collection were independently done by two researchers. We searched clinical trial registry platform to supplement the outcomes list extracted by systematic review. Then, we conducted a three-round Delphi survey. The stakeholders were hyperlipidemia patients, clinicians or researchers, in either CM/integrated Chinese or Western medicine, clinical pharmacy, clinical epidemiology or statisticians, or editors of important relevant journals and an ethicist. They used a 9-point Likert scale to determine how important they felt each outcome was in determining treatment success. A consensus meeting was held to confirm the final COS, based on the Delphi survey results.Results: We identified a total of 433 outcomes from 3,547 articles, and 28 outcomes from 367 registered trials. After standardization, we selected 71 outcomes to develop a preliminary outcome list for further consensus. After three Delphi survey rounds and one consensus meeting, the most important outcomes were determined for COS-CM-Hyperlipidemia. It included cardiovascular events, low-density lipoprotein cholesterol, risk of cardiovascular disease, total cholesterol, carotid intima-media thickness, high-density lipoprotein cholesterol, triglycerides, cerebrovascular events, adverse drug reactions and patient-reported symptoms.Conclusion: COS-CM-Hyperlipidemia may improve outcome reporting consistency in clinical trials. Further work is needed to explore the optimal methods for measuring these outcomes.Registration: The Core Outcome Measures in Effectiveness Trials Initiative (COMET): http://www.cometinitiative.org/studies/details/983. Registered on 25 April 2017.</p