Integrated piezoresistive sensors for atomic force-guided scanning Hall probe microscopy

We report the development of an advanced sensor for atomic force-guided scanning Hall probe microscopy whereby both a high mobility heterostructure Hall effect magnetic sensor and an n-Al0.4Ga0.6As piezoresistive displacement sensor have been integrated in a single III-V semiconductor cantilever. This allows simple operation in high-vacuum/variable-temperature environments and enables very high magnetic and topographic resolution to be achieved simultaneously. Scans of magnetic induction and topography of a number of samples are presented to illustrate the sensor performance at 300 and 77 K. (C) 2003 American Institute of Physics

Micromachined III-V cantilevers for AFM-tracking scanning Hall probe microscopy

In this paper we report the development of a new III-V cantilever-based atomic force sensor with piezoresistive detection and an integrated Hall probe for scanning Hall probe microscopy. We give detailed descriptions of the fabrication process and characterization of the new integrated sensor, which will allow the investigation of magnetic samples with no sample preparation at both room and cryogenic temperatures. We also introduce a novel piezoresistive material based on the ternary alloy n+-Al0.4Ga0.6As which allows us to achieve a cantilever deflection sensitivity ΔR/(RΔz) = 2 × 10-6 Å-1 at room temperature

A Tale of Three Species: Adaptation of Sodalis glossinidius to Tsetse Biology, Wigglesworthia Metabolism, and Host Diet.

The tsetse fly is the insect vector for the Trypanosoma brucei parasite, the causative agent of human African trypanosomiasis. The colonization and spread of the trypanosome correlate positively with the presence of a secondary symbiotic bacterium, Sodalis glossinidius The metabolic requirements and interactions of the bacterium with its host are poorly understood, and herein we describe a metabolic model of S. glossinidius metabolism. The model enabled the design and experimental verification of a defined medium that supports S. glossinidius growth ex vivo This has been used subsequently to analyze in vitro aspects of S. glossinidius metabolism, revealing multiple unique adaptations of the symbiont to its environment. Continued dependence on a sugar, and the importance of the chitin monomer N-acetyl-d-glucosamine as a carbon and energy source, suggests adaptation to host-derived molecules. Adaptation to the amino acid-rich blood diet is revealed by a strong dependence on l-glutamate as a source of carbon and nitrogen and by the ability to rescue a predicted l-arginine auxotrophy. Finally, the selective loss of thiamine biosynthesis, a vitamin provided to the host by the primary symbiont Wigglesworthia glossinidia, reveals an intersymbiont dependence. The reductive evolution of S. glossinidius to exploit environmentally derived metabolites has resulted in multiple weaknesses in the metabolic network. These weaknesses may become targets for reagents that inhibit S. glossinidius growth and aid the reduction of trypanosomal transmission.IMPORTANCE Human African trypanosomiasis is caused by the Trypanosoma brucei parasite. The tsetse fly vector is of interest for its potential to prevent disease spread, as it is essential for T. brucei life cycle progression and transmission. The tsetse's mutualistic endosymbiont Sodalis glossinidius has a link to trypanosome establishment, providing a disease control target. Here, we describe a new, experimentally verified model of S. glossinidius metabolism. This model has enabled the development of a defined growth medium that was used successfully to test aspects of S. glossinidius metabolism. We present S. glossinidius as uniquely adapted to life in the tsetse, through its reliance on the blood diet and host-derived sugars. Additionally, S. glossinidius has adapted to the tsetse's obligate symbiont Wigglesworthia glossinidia by scavenging a vitamin it produces for the insect. This work highlights the use of metabolic modeling to design defined growth media for symbiotic bacteria and may provide novel inhibitory targets to block trypanosome transmission

A Tale of Three Species: Adaptation of Sodalis glossinidius to Tsetse Biology, Wigglesworthia Metabolism, and Host Diet.

The tsetse fly is the insect vector for the Trypanosoma brucei parasite, the causative agent of human African trypanosomiasis. The colonization and spread of the trypanosome correlate positively with the presence of a secondary symbiotic bacterium, Sodalis glossinidius The metabolic requirements and interactions of the bacterium with its host are poorly understood, and herein we describe a metabolic model of S. glossinidius metabolism. The model enabled the design and experimental verification of a defined medium that supports S. glossinidius growth ex vivo This has been used subsequently to analyze in vitro aspects of S. glossinidius metabolism, revealing multiple unique adaptations of the symbiont to its environment. Continued dependence on a sugar, and the importance of the chitin monomer N-acetyl-d-glucosamine as a carbon and energy source, suggests adaptation to host-derived molecules. Adaptation to the amino acid-rich blood diet is revealed by a strong dependence on l-glutamate as a source of carbon and nitrogen and by the ability to rescue a predicted l-arginine auxotrophy. Finally, the selective loss of thiamine biosynthesis, a vitamin provided to the host by the primary symbiont Wigglesworthia glossinidia, reveals an intersymbiont dependence. The reductive evolution of S. glossinidius to exploit environmentally derived metabolites has resulted in multiple weaknesses in the metabolic network. These weaknesses may become targets for reagents that inhibit S. glossinidius growth and aid the reduction of trypanosomal transmission.IMPORTANCE Human African trypanosomiasis is caused by the Trypanosoma brucei parasite. The tsetse fly vector is of interest for its potential to prevent disease spread, as it is essential for T. brucei life cycle progression and transmission. The tsetse's mutualistic endosymbiont Sodalis glossinidius has a link to trypanosome establishment, providing a disease control target. Here, we describe a new, experimentally verified model of S. glossinidius metabolism. This model has enabled the development of a defined growth medium that was used successfully to test aspects of S. glossinidius metabolism. We present S. glossinidius as uniquely adapted to life in the tsetse, through its reliance on the blood diet and host-derived sugars. Additionally, S. glossinidius has adapted to the tsetse's obligate symbiont Wigglesworthia glossinidia by scavenging a vitamin it produces for the insect. This work highlights the use of metabolic modeling to design defined growth media for symbiotic bacteria and may provide novel inhibitory targets to block trypanosome transmission

Effect of nano-Al2O3 addition on the microstructure and erosion wear of HVOF sprayed NiCrSiB coatings

Development of nanostructured high velocity oxy-fuel (HVOF) coatings with low porosity, high strength and increased wear resistance is still in its infancy. Combining nanoparticles with conventional microscale powders are increasingly being investigated to use with feedstock materials for thermal spray processes. Accordingly, this work investigates the addition of nano-Al2O3 particles on the microstructure and erosion wear of NiCrSiB HVOF coating in a stainless steel (AISI 304) substrate. Particle analysis of the NiCrSiB feedstock was conducted and the maximum allowable addition of Al2O3 nanoparticles have been identified using the 'mass mixture ratio' model considering both the particle size and density. Consequently, two cases are considered and their performance analysed: a maximum allowable case of 1.4 wt%, followed by a 0.17 wt% addition of nano-Al2O3 with NiCrSiB. Scanning Electron Microscope (SEM), Energy Dispersive Spectroscopy (EDS) and x-ray Diffraction (XRD) analysis were employed to inform the microstructure, material composition and phase spectrum of the resulting coatings. Subsequently, the nanostructured coating was exposed to both a pull-off adhesion strength test and hot air jet (450 °C) hard particle erosion to characterise its performance. It was found that the microhardness of the HVOF NiCrSiB coating improved from 576 HV0.3 to 748 HV0.3 with the addition of 1.4 wt% nano-Al2O3. Furthermore, the nanostructured coating also exhibited high erosion resistance at a 90° erodent impact angle. The increase in erosion wear resistance was due to the increase in the hardness as a result of the nano-Al2O3 addition.Published onlin

The MBE growth and optimization of high performance terahertz frequency quantum cascade lasers

The technique of molecular beam epitaxy has recently been used to demonstrate the growth of terahertz frequency GaAs/AlGaAs quantum cascade lasers (QCL) with Watt-level optical output powers. In this paper, we discuss the critical importance of achieving accurate layer thicknesses and alloy compositions during growth, and demonstrate that precise growth control as well as run-to-run growth reproducibility is possible. We also discuss the importance of minimizing background doping level in maximizing QCL performance. By selecting high-performance active region designs, and optimizing the injection doping level and device fabrication, we demonstrate total optical (two-facet) output powers as high as 1.56 W

Systems analyses reveal the resilience of Escherichia coli physiology during accumulation and export of the nonnative organic acid citramalate

© 2019 Webb et al. Productivity of bacterial cell factories is frequently compromised by stresses imposed by recombinant protein synthesis and carbon-to-product conversion, but little is known about these bioprocesses at a systems level. Production of the unnatural metabolite citramalate in Escherichia coli requires the expression of a single gene coding for citramalate synthase. Multiomic analyses of a fermentation producing 25 g liter1 citramalate were undertaken to uncover the reasons for its productivity. Metabolite, transcript, protein, and lipid profiles of high-cell-density, fed-batch fermentations of E. coli expressing either citramalate synthase or an inactivated enzyme were similar. Both fermentations showed downregulation of flagellar genes and upregulation of chaperones IbpA and IbpB, indicating that these responses were due to recombinant protein synthesis and not citramalate production. Citramalate production did not perturb metabolite pools, except for an increased intracellular pyruvate pool. Gene expression changes in response to citramalate were limited; none of the general stress response regulons were activated. Modeling of transcription factor activities suggested that citramalate invoked a GadW-mediated acid response, and changes in GadY and RprA regulatory small RNA (sRNA) expression supported this. Although changes in membrane lipid composition were observed, none were unique to citramalate production. This systems analysis of the citramalate fermentation shows that E. coli has capacity to readily adjust to the redirection of resources toward recombinant protein and citramalate production, suggesting that it is an excellent chassis choice for manufacturing organic acids. IMPORTANCE Citramalate is an attractive biotechnology target because it is a precursor of methylmethacrylate, which is used to manufacture Perspex and other high-value products. Engineered E. coli strains are able to produce high titers of citramalate, despite having to express a foreign enzyme and tolerate the presence of a nonnative biochemical. A systems analysis of the citramalate fermentation was undertaken to uncover the reasons underpinning its productivity. This showed that E. coli readily adjusts to the redirection of metabolic resources toward recombinant protein and citramalate production and suggests that E. coli is an excellent chassis for manufacturing similar small, polar, foreign molecules.We thank the Biotechnology and Biological Sciences Research Council UK and InnovateUK for funding (Industrial Biotechnology Catalyst BB/N01040X/1) and the Centre of Excellence in Mass Spectrometry funded by Science City York (Yorkshire Forward, EP/K039660/1, EP/M028127/1)

Development of selective agonists and antagonists of P2Y receptors

Although elucidation of the medicinal chemistry of agonists and antagonists of the P2Y receptors has lagged behind that of many other members of group A G protein-coupled receptors, detailed qualitative and quantitative structure–activity relationships (SARs) were recently constructed for several of the subtypes. Agonists selective for P2Y1, P2Y2, and P2Y6 receptors and nucleotide antagonists selective for P2Y1 and P2Y12 receptors are now known. Selective nonnucleotide antagonists were reported for P2Y1, P2Y2, P2Y6, P2Y11, P2Y12, and P2Y13 receptors. At the P2Y1 and P2Y12 receptors, nucleotide agonists (5′-diphosphate derivatives) were converted into antagonists of nanomolar affinity by altering the phosphate moieties, with a focus particularly on the ribose conformation and substitution pattern. Nucleotide analogues with conformationally constrained ribose-like rings were introduced as selective receptor probes for P2Y1 and P2Y6 receptors. Screening chemically diverse compound libraries has begun to yield new lead compounds for the development of P2Y receptor antagonists, such as competitive P2Y12 receptor antagonists with antithrombotic activity. Selective agonists for the P2Y4, P2Y11, and P2Y13 receptors and selective antagonists for P2Y4 and P2Y14 receptors have not yet been identified. The P2Y14 receptor appears to be the most restrictive of the class with respect to modification of the nucleobase, ribose, and phosphate moieties. The continuing process of ligand design for the P2Y receptors will aid in the identification of new clinical targets