Combinatorial Mutasynthesis of Scrambled Beauvericins,Cyclooligomer Depsipeptide Cell Migration Inhibitors from Beauveria bassiana

Fungal cyclooligomer depsipeptides such as beauvericin, bassianolide, and enniatins display antibiotic, antifungal, insecticidal, broad‐spectrum cancer cell antiproliferative, and cell migration inhibitory activities. We have identified a gene encoding a novel enzyme, ketoisovalerate reductase (KIVR), which is the sole provider of D ‐hydroxyisovalerate (D ‐Hiv), a common precursor for cyclooligomer depsipeptide biosynthesis in Beauveria bassiana. KIVR and related hypothetical oxidoreductases encoded in fungal genomes are similar to ketopantoate reductases but not to D ‐hydroxycarboxylate dehydrogenases. We demonstrate that a KIVR knockout B. bassiana strain can be used for the efficient mutasynthesis of unnatural beauvericin congeners. Simultaneous feeding of precursor analogues enabled the combinatorial mutasynthesis of scrambled beauvericins, some assembled entirely from unnatural precursors. The effects of the introduced structural changes on the antiproliferative and cell migration inhibitory activities of these analogues were evaluated.     

Functional Chromatography Reveals Three Natural Products that Target the Same Protein with Distinct Mechanisms of Action

Access to lead compounds with defined molecular targets continues to be a barrier to the translation of natural product resources. As a solution, we developed a system that uses discrete, recombinant proteins as the vehicles for natural product isolation. Here, we describe the use of this functional chromatographic method to identify natural products that bind to the AAA+ chaperone, p97, a promising cancer target. Application of this method to a panel of fungal and plant extracts identified rheoemodin, 1‐hydroxydehydroherbarin, and phomapyrrolidone A as distinct p97 modulators. Excitingly, each of these molecules displayed a unique mechanism of p97 modulation. This discovery provides strong support for the application of functional chromatography to the discovery of protein modulators that would likely escape traditional high‐throughput or phenotypic screening platforms.     

Two-Phase Flow and Heat Transfer During Chilldown of a Simulated Flexible Metal Hose Using Liquid Nitrogen

For many industrial, medical and space technologies, cryogenic fluids play irreplaceable roles. When any cryogenic system is initially started, it must go through a transient chill down period prior to normal operation. Chilldown is the process of introducing the cryogenic liquid into the system, and allowing the system components to cool down to several hundred degrees below the ambient temperature. The chilldown process is an important initial stage before a system begins functioning. The objective of this paper is to investigate the chilldown process associated with a flexible hose that was simulated by a channel with saw-teeth inner wall surface structure in the current study. We have investigated the fundamental physics of the two-phase flow and quenching heat transfer during cryogenic chilldown inside the simulated flexible hose through flow visualization, data measurement and analysis. The flow pattern developed inside the channel was recorded by a high speed camera for flow pattern investigation. The experimental results indicate that the chilldown process that is composed of unsteady vapor-liquid two-phase flow and phase-change heat transfer is modified by the inner wall surface wavy structure. Based on the measurement of the channel wall temperature, the teeth structure and the associated cavities generally reduce the heat transfer efficiency compared to the straight hose. Furthermore, based on the measured data, a complete series of correlations on the heat transfer coefficient for each heat transfer regime was developed and reported.     

Effect of areal density and fiber orientation on the deformation of thermomechanical bonds in a nonwoven fabric

This study proposes a novel method to mechanically characterize the performance of individual bonds in low‐density, thermomechanically bonded nonwoven fabrics. Commercial bicomponent, polyethylene/polypropylene (PE/PP), nonwoven fabric was laser cut into bowtie‐shaped specimens for uniaxial tensile testing so that the central region of each specimen contained an individual bond. Three groups, each composed of 20 specimens, were tested with their longitudinal axes oriented along the machine direction (MD), the cross direction (CD), and at 45° between these two directions (DD). Prior to testing, the intrinsic variation in areal density and fiber orientation in the region surrounding the individual bond were quantified via orientation and relative basis weight parameters. During testing, images of the specimens were acquired to determine the occurrence of fiber breakage, bond deformation, and bond cohesive failure. Maximum force, stiffness, and orientation parameters were found to be significantly different among the three specimen groups (p < 0.01) but the relative basis weight was not (p > 0.01). The stiffness and maximum load were linearly correlated with both the areal density and fiber orientation. Pre‐existing voids or windows within the bond lowered the maximum force for specimens with the longitudinal axes aligned with the MD. These voids had no influence on the maximum force achieved by the specimens aligned with the CD and DD. The bonds in these specimens were observed to deform less than the bonds in the specimens with the longitudinal axes aligned with the MD. The results indicate the importance of the fiber structure surrounding the bond on the tensile properties, deformation and failure mode of individual bonds within the nonwoven fabric. POLYM. ENG. SCI., 59:311–322, 2019. © 2018 Society of Plastics Engineers     

Effect of sodium metabisulphide on ethanol production in coconut inflorescence sap

The addition of up to 200 mg l^?1 of sodium metabisulphite to coconut inflorescence sap was found to suppress the non-ethanol producing micro-organisms and permit ethanol production by pure yeast cultures to different extents. At metabisulphite concentrations higher than 150 mg l^?1 the ethanol yields from sap fermented with a natural inoculum increased under laboratory conditions. In the field, introduction of sodium metabisulphite to sap collecting pots gave maximum ethanol yield at a concentration of 188 mg l^?1 and on fermenting for 36 days. A response function was derived, based on field observations, to predict the ethanol yields at different sodium metabisulphite concentrations up to 325 mg l^?1 and durations of fermentation 1 to 5 days.     

A 9-GHz 65-nm Intel® Pentium 4 Processor Integer Execution Unit

This paper describes a fourth generation Intel Pentium 4 processor integer execution core operating at 9 GHz in a 1.3-V, 65-nm CMOS technology at 70degC. Low-voltage-swing circuits of the 90-nm design are replaced by: 1) 2times frequency fast clock (FCLK)-optimized domino clocking scheme; 2) segmented arithmetic and logic unit (ALU) front-end multiplexer; 3) sparse-tree ALU adder; 4) merged add/subtract sparse-tree address generation unit (AGU) design; 5) speculative RC-delay-optimized rotator; and 6) single-rail L0 cache and alignment multiplexer, resulting in 8.4% reduction in integer core normalized active power and 42% reduction in normalized leakage power. The use of standard domino/static tools and methodologies lowers design complexity, reducing development cost and time. The redesign also reduces integer core thermal density, resulting in an 8degC reduction in CPU operating temperature     

Preparation and characterization of electronically conducting polypyrrole-montmorillonite nanocomposite and its potential application as a cathode material for oxygen reduction

Simple wet chemical processes were deployed to prepare low-cost conducting nanocomposites based on natural clays with 2:1 layered structures such as sodium montmorillonite (MMT). Ce(IV) modified MMT was used for the spontaneous polymerization of pyrrole within clay interlayers. The resulted clay-conducting polypyrrole nanocomposites containing the reduced form of the oxidising agent, have been extensively characterized by X-ray diffraction (XRD) technique for interlayer spacing variations and by Fourier transform infra red (FT-IR) spectroscopy to study the interactions between the clay and polymer functional groups. DC polarization technique with both blocking and non-blocking electrodes was used to distinguish between the ionic and electronic transport numbers and to recognize the type of mobile ionic species. AC impedance analysis further resolved the electrical conduction of these materials. Bulk conductivity analysis implied that the polypyrrole (PPY) formed within Ce(IV) modified MMT posses dominant electronic conductivity. The low-cost, light-weight and stable polymer-clay nanocomposite prepared by Ce(IV) intercalated MMT, [Ce(III)-PPY-MMT], seems to be a promising cathode material for oxygen reduction and hence may find applications in fuel cell industries.     

New structural insight for antimony(III)-tartrate

Theoretical calculations (density functional theory and ab initio (MP2)) and nuclear magnetic resonance experiments reveal a new metal-oxygen-bridged isomeric form for antimony(III)-l-tartrate that co-exists in solution and in the gas phase with its crystallographically-determined structure.     

Low-voltage swing logic circuits for a Pentium/spl reg/ 4 processor integer core

The Pentium/spl reg/ 4 processor architecture uses a 2/spl times/ frequency core clock to implement low latency integer operations. Low-voltage-swing (LVS) logic circuits implemented in 90-nm technology meet the frequency demands of a third-generation integer-core design.     

Effects of extrusion and expelling on the nutritional quality of conventional and Kunitz trypsin inhibitor-free soybeans

Two chick growth experiments and a precision-fed cockerel digestibility assay were conducted to evaluate the effect of extrusion and expelling on the nutritive value of conventional (CSB) and Kunitz trypsin inhibitor-free (KFSB) soybeans. In the first experiment, performance of chicks fed CSB or KFSB autoclaved at 121 C was similar to that of chicks fed CSB or KFSB extruded at 138 C. The effect of extrusion temperature on protein quality of the soybeans was evaluated in the second experiment. Eleven corn-soybean diets were formulated to contain one of the following: CSB extruded at 104, 121, 138, or 154 C; KFSB extruded at 104, 121, or 138 C; CSB extruded at 121, 138, or 154 C followed by processing through an expeller; and commercial dehulled solvent-extracted soybean meal (SBM). All diets contained 20% crude protein and the same amount of soybean oil and were fed to chicks from 7 to 21 days of age. The CSB extruded at 104 or 121 C and KFSB extruded at 104 C yielded depressed growth and feed efficiency compared with SBM. Performance of chicks on the other treatments was similar to that of chicks fed SBM. Pancreas weight (as a percentage of BW) decreased as extrusion temperature increased, with the response being greater for CSB. Growth performance was greater and pancreas weights were lower for chicks fed KFSB extruded at 104 or 121 C compared with those of chicks fed CSB extruded at the same temperatures. Expelling improved weight gain and feed efficiency when CSB was extruded at 121 C. A 48-h digestibility assay with cecectomized cockerels indicated that digestibility of amino acids in CSB and KFSB increased as extrusion temperature increased and that digestibilities of amino acids in CSB extruded at 104 or 121 C were lower than those in KFSB extruded at the same temperatures. Results of this study indicated that extrusion of CSB at 138 to 154 C or extrusion of KFSB at 121 to 138 C yields protein quality similar to that of SBM.