Type S Non-Ribosomal Peptide Synthetases for the Rapid Generation of Tailormade Peptide Libraries**

Bacterial natural products in general, and non-ribosomally synthesized peptides in particular, are structurally diverse and provide us with a broad range of pharmaceutically relevant bioactivities. Yet, traditional natural product research suffers from rediscovering the same scaffolds and has been stigmatized as inefficient, time-, labour- and cost-intensive. Combinatorial chemistry, on the other hand, can produce new molecules in greater numbers, cheaper and in less time than traditional natural product discovery, but also fails to meet current medical needs due to the limited biologically relevant chemical space that can be addressed. Consequently, methods for the high throughput generation of new natural products would offer a new approach to identifying novel bioactive chemical entities for the hit to lead phase of drug discovery programs. As a follow-up to our previously published proof-of-principle study on generating bipartite type S non-ribosomal peptide synthetases (NRPSs), we now envisaged the de novo generation of non-ribosomal peptides (NRPs) on an unreached scale. Using synthetic zippers, we split NRPSs in up to three subunits and rapidly generated different bi- and tripartite NRPS libraries to produce 49 peptides, peptide derivatives, and de novo peptides at good titres up to 145 mg L⁻¹. A further advantage of type S NRPSs not only is the possibility to easily expand the created libraries by re-using previously created type S NRPS, but that functions of individual domains as well as domain-domain interactions can be studied and assigned rapidly.     

Two new cycloartanes from the leaves of Combretum quadrangulare growing in Vietnam and their biological activities

Two new cycloartanes, combretanones G and H (1 and 2), were isolated from the leaves of Combretum quadrangulare. Their structures were elucidated by applying a set of spectroscopic methods, while their relative configurations were determined using DFT-NMR chemical shift calculations and subsequent assignment of DP4 probabilities. Compounds 1 and 2 are C-23/C-24 stereoisomers of the previously-reported euphonerin E. Both exhibited moderate cytotoxicity against three human cancer cell lines. Compound 2 was shown to be a potent antiparasitic. Our results confirm the traditional medicinal uses of Combretum quadrangulare in Vietnam.     

On the eddy diffusivities for momentum and heat

Summary From a simple consideration, the eddy diffusivities for momentum and heat are shown to be equal in terms of statistical properties of turbulence. A universal semi-empirical expression for the eddy diffusivities in a turbulent shear flow is obtained in terms of the distance from the solid boundary and flow properties.     

Laminar natural convection heat transfer from vertical plate to power-law fluid

Summary Approximate solutions for laminar natural convection heat transfer between a vertical plate and a power-law fluid with high Prandtl number were obtained using an integral method for cases with various types of boundary conditions. The results were found in good agreement with available experimental evidence.Nomenclature a exponent defined by equations (28) and (29) - A, B, C, D, E constants defined by equations (15) to (19) - C ₁, C ₂, M ₁, M ₂ coefficients for Nusselt number expression defined by (32b), (33b) - f temperature difference, equal to T _s–T - f ⁺ dimensionless temperature difference - g gravitational acceleration - Gr Grashof number defined by (25), (50) and (66), respectively - H heat flux at plate surface - h _x local heat transfer coefficient - K consistency index for Power-law fluid - k thermal conductivity of fluid - K ₁, K ₂ constants defined by (50) and (51) - L height of plate - n flow behavior index for Power-law fluid - P a quantity defined by (54a) - T temperature - T _s plate temperature - T temperature of the bulk of fluid - s constant given by (35) - u velocity component along x-direction - u _x maximum velocity induced by natural convection current, (10) - v velocity component along y-direction - x distance measured along direction parallel to that of gravitational force - x ⁺ dimensionless quantity, defined as x/L - y distance measured away from plate - Nu _x local Nusselt number - Nu _av average Nusselt number - Pr Prandtl number defined by (24) - T temperature difference according to boundary conditions - thermal diffusivity of fluid - coefficient of thermal expression of fluid - boundary layer thickness - ⁺ dimensionless boundary layer thickness - dimensionless velocity profile - dimensionless variable, defined as y/ - dimensionless temperature difference     

Chemical immobilization of crosslinked polymeric ionic liquids on nitinol wires produces highly robust sorbent coatings for solid-phase microextraction

Super elastic nitinol (NiTi) wires were exploited as highly robust supports for three distinct crosslinked polymeric ionic liquid (PIL)-based coatings in solid-phase microextraction (SPME). The oxidation of NiTi wires in a boiling (30% w/w) H₂O₂ solution and subsequent derivatization in vinyltrimethoxysilane (VTMS) allowed for vinyl moieties to be appended to the surface of the support. UV-initiated on-fiber copolymerization of the vinyl-substituted NiTi support with monocationic ionic liquid (IL) monomers and dicationic IL crosslinkers produced a crosslinked PIL-based network that was covalently attached to the NiTi wire. This alteration alleviated receding of the coating from the support, which was observed for an analogous crosslinked PIL applied on unmodified NiTi wires. A series of demanding extraction conditions, including extreme pH, pre-exposure to pure organic solvents, and high temperatures, were applied to investigate the versatility and robustness of the fibers. Acceptable precision of the model analytes was obtained for all fibers under these conditions. Method validation by examining the relative recovery of a homologous group of phthalate esters (PAEs) was performed in drip-brewed coffee (maintained at 60 °C) by direct immersion SPME. Acceptable recoveries were obtained for most PAEs in the part-per-billion level, even in this exceedingly harsh and complex matrix.     

Transient dynamic analysis of cracked structures with multiple contact pairs using generalized HSNC

Nonlinear Dynamics - The development of efficient computational methods for cracked structures is critical in the fields of civil, mechanical, and aerospace engineering since the influence of...     

Miniature Wet-Bulb Technique for Measuring Gas Concentrations in Condensing or Evaporating Systems

Abstract

An analysis is presented to show that a miniature wet-bulb/dry-bulb probe can provide easy, rapid, and accurate point measurements of noncondensable gas concentrations in condensing or evaporating systems. The probe consists of a liquid-soaked porous sphere as small as 0.5 mm in diameter with a fine-gauge thermocouple embedded at its center. Performance of the probe is shown to improve with decreasing wet-bulb size. Measurements of only the total pressure and point wet-bulb temperature are needed to determine the local gas concentration for most gas-vapor systems. The use of the technique in systems with steep concentration gradients is demonstrated by application to the well-studied problem of the gas-loaded two-phase thermosyphon. 195pt     

Enhanced lithium electrochromism of atmospheric pressure plasma jet-synthesized tungsten/molybdenum oxide films for flexible electrochromic devices

Enhanced lithium electrochromic performances of mixed organo-tungsten oxide (W _x O _y C _z )/organo-molybdenum oxide (Mo _x O _y C _z ) films by a rapid codeposition onto 40 Ω/□ flexible polyethylene terephthalate/indium tin oxide substrates at a short exposed duration of 23 s using an atmospheric pressure plasma jet (APPJ) at various mixed concentrations of hexacarbonyl precursors [W(CO)₆ and Mo(CO)₆] are investigated. The flexible organo-tungsten–molybdenum oxide (WMo _x O _y C _z ) films demonstrated noteworthy electrochromic performance for 200 cycles of reversible Li⁺ ion intercalation and deintercalation in a 1 M LiClO₄–propylene carbonate electrolyte by the switching measurements of potential sweep from ?1 to 1 V at a scan rate of 50 mV/s and the potential step at ?1 and 1 V, even after being bent 360^o around a 2.5-cm diameter rod for 1,000 cycles. The optical modulation (ΔT) of 61.3 % for MoO _y C _z films at a wavelength of 795.6 nm was significantly improved up to 72.5 % for WMo _x O _y C _z films cosynthesized with an APPJ.