Rapid On-Resin N-Formylation of Peptides as One-Pot Reaction

N-formylation is a common pre- and post-translational modification of the N-terminus or the lysine side chain of peptides and proteins that plays a role in the initiation of immune responses, gene expression, or epigenetics. Despite its high biological relevance, protocols for the chemical N-formylation of synthetic peptides are scarce. The few available methods are elaborate in their execution and the yields are highly sequence-dependent. We present a rapid, easy-to-use one-pot procedure that runs at room temperature and can be used to formylate protected peptides at both the N-terminus and the lysine side chain on the resin in near-quantitative yields. Only insensitive, storage-stable standard chemicals – formic acid, acetic anhydride, pyridine and DMF – are used. Formylation works for both short and long peptides of up to 34 amino acids and over the spectrum of canonical amino acids.     

Preparation of DOPO-derived magnesium phosphate whisker and its synergistic effect with ammonium polyphosphate on the flame retardancy and mechanical property of epoxy resin

In this study, a magnesium phosphate whisker (DPM-H) was synthesized by the acid–base neutralization reaction between magnesium hydroxide and 10-hydroxy-9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO-OH) at 120°C. A new synergistic intumescent flame retardant (IFR) for epoxy resin (EP), which was composed of DPM-H and ammonium polyphosphate (APP) was thoroughly studied. When the IFR loading was 8%, with the DPM-H to APP weight ratio at 1:7, the prepared flame-retardant EP (EPDA-2) passed the vertical burning tests (UL-94) V-0 rating and obtained the limiting oxygen index (LOI) value of 29.3%. Microscale combustion calorimetry (MCC) results showed that the total heat release (THR) of EPDA-2 reduced by 32.1% compared with pure EP. Meanwhile, the addition of DPM-H can partially solve the problem of the decrease of the EP mechanical property caused by the addition of APP. Compared with the flame-retardant EP with the 8% loading of APP, the impact strength of EPDA-2 increased 152.3%.     

Serendipitous Identification of a Covalent Activator of Liver Pyruvate Kinase

Enzymes are effective biological catalysts that accelerate almost all metabolic reactions in living organisms. Synthetic modulators of enzymes are useful tools for the study of enzymatic reactions and can provide starting points for the design of new drugs. Here, we report on the discovery of a class of biologically active compounds that covalently modifies lysine residues in human liver pyruvate kinase (PKL), leading to allosteric activation of the enzyme (EC₅₀=0.29 μM). Surprisingly, the allosteric activation control point resides on the lysine residue K282 present in the catalytic site of PKL. These findings were confirmed by structural data, MS/MS experiments, and molecular modelling studies. Altogether, our study provides a molecular basis for the activation mechanism and establishes a framework for further development of human liver pyruvate kinase covalent activators.     

Leakage of Metallic Ball Seat Valves with Anisotropic Surfaces

Metallic ball seat valves are an essential component of many hydraulic systems. They are used for many different purposes such as pressure relief valves or check valves. Despite their universal usage, their sealing mechanism is not yet fully understood. In previous works, a successful method for the simulation of the fluid leakage of metallic ball seat valves has been developed and confirmed experimentally. The method is based on Persson's contact mechanics theory, which is based on surface roughness power spectrum C(q). This theory takes a wide range of roughness values at different length scales into account. The previous method has been restricted to isotropic surfaces, but most surfaces of practical interest are highly anisotropic. A method for the calculation of pressure flow factors using Persson's method is presented. Based on these, a model for the leakage calculation can be developed. The simulation results are validated using an experiment.     

Lipase-catalyzed transesterification of phosphatidylcholine at controlled water activity

The incorporation of a free fatty acid into thesn-1 position of phosphatidylcholine by lipase-catalyzed transesterification was investigated. The thermodynamic water activity of both the enzyme preparation and the substrate solution was adjusted to the same value prior to the reaction. The reaction rate increased with increasing water activity but the yield of modified phosphatidylcholine decreased due to hydrolysis. By using a large excess of the free fatty acid (heptadecanoic acid), the hydrolysis reaction was slowed down, so a higher yield was obtained at a given degree of incorporation. The best results were obtained withRhizopus arrhizus lipase immobilized by adsorption on a polypropylene support. With this preparation, a yield of 60% and nearly 50% incorporation of heptadecanoic acid (100% incorporation in thesn-1 position) was obtained at a water activity of 0.064. The enzyme preparation had good operational stability and position specificity. Little incorporation (<1%) was observed in thesn-2 position, when almost all the fatty acid in thesn-1 position was exchanged.     

Die design for rigid PVC—the effect of die land length on extrudate swell

PVC profile extrusion compounds have a unique morphology. While other polymers gradually decrease in extrusion die swell with increasing length/thickness (L/D) ratio, PVC profile extrusion compounds have a low die swell, quite independent of the die's L/D ratio in the range of 5 to 20. The fact that the die land length can be changed without changing the extrudate swell is an important consideration, which makes die design and balancing dies simpler and easier for PVC profile extrusion compounds. While other polymers substantially increase extrudate swell with increased shear rate, the swell of the PVC profile compounds is not much affected by shear or extrusion rate. This unique behavior allows wider processing latitude in profile extrusion and faster extrusion rates than with other polymers. Another unique factor in the rheology of PVC profile extrusion compounds is that extrusion die swell increases with increasing melt temperature, while other polymers have decreasing die swell with increasing melt temperature. The unusual rheology of PVC profile extrusion compounds is attributed to its unique melt morphology, where the melt flow units are 1 um bundles and molecules that have low surface to surface interaction and entanglement at low processing temperatures but increased melting and increased entanglement at higher processing temperatures. Other polymers, unlike PVC, have melt flow at the molecular level.     

正确表面预处理对涂料干膜杀菌剂抗微生物活性的影响

通过使用墙体杀菌清洁与非杀菌清洁后涂料干膜的性能比较，评价了杀菌清洗对提高涂料干膜性能的有效性，揭示了怎样用杀菌清洁提高杀菌系统的特性。同时，比较了传统杀菌剂和新式杀菌剂的性能差别。     

Antagonism of croton oil inflammation by topical emu oil in CD-1 mice

Emu oil is derived from the emu (Dromaius novaehollandiae), which originated in Australia, and has been reported to have anti-inflammatory properties. Inflammation was induced in anesthetized CD-1 mice by applying 50 μL of 2% croton oil to the inner surface of the left ear. After 2 h, the area was treated with 5μL of emu, fish, flaxseed, olive, or liquified chicken fat, or left untreated. Animals were euthanized at 6 h postapplication of different oils, and earplugs (FP) and plasma samples were collected. Inflammation was evaluated by change in earlobe thickness, increase in weight of EP tissue (compared to the untreated ear), and induction in cytokines interleukin (IL)-1α and tumor necrosis factor-α (TNF-α) in EP homogenates. Al-though reductions relative to control (croton oil) were noted for all treatments, auricular thickness and EP weights were, significantly reduced (−72 and −71%, respectively) only in the emu oil-treated group. IL-1α levels in homogenates of auricular tissue were significantly reduced in the fish oil (−57%) and emu oil (−70%) groups relative to the control group. The cytokine TNF-α from auricular homogenates was significantly reduced in the olive oil (−52%) and emu oil (−60%) treatment groups relative to the control group. Plasma cytokine levels were not changed by croton oil treatment. Although auricular thickness and weight were significantly correlated with each other (r=0.750, P<0.003), auricular thickness but not weight was significantly correlated with cytokine IL-1α (r=0.750, P<0.006) and TNF-α (r=0.690, P<0.02). These studies indicate that topical emu oil has anti-inflammatory properties in the CD-1 mouse that are associated with decreased auricular thickness and weight, and with the cytokines IL-1α and TNF-α.     

Enhancing dead end filtration throughput using a non-traditional liquid handling procedure

The dead end filtration of dilute protein solutions is normally conducted with either a constant pressure or constant rate fluid delivery system. However both approaches often fall short in using all the available capacity of the filter. A novel automated fluid handling system has been recently developed by SciLog Inc, USA, which can increase the DEF yield by up to 35%. Karl Schick, director of research & development, presents and discusses throughput data supporting this claim.     

A new ‘tailor-made’ methodology for the mechanical behaviour analysis of rubber-like materials: I. Kinematics measurements using a digital speckle extensometry

This paper is the first part of a work devoted to the setting-up of a methodology for the mechanical behaviour characterization of rubber-like materials, using a digital speckle extensometer. We present here the experimental approach, specific to large strain measurements. The proposed method is based on in-plane kinematics measurements using an optical extensometer. The whole two-dimensional field of in-plane displacements is obtained by a digital image processing. We discuss then the correlation calculations and how to achieve the optimal subset matching. Next, we specify how to derive the principal stretch ratios, and the accuracy on these components, issued from a subsequent numerical calibration.Finally, we present experimental data dealing with a carbon black, filled natural rubber, issued from uniaxial traction tests, pure shear tests, and tensile tests performed on double-edge notched tensile specimens.