The division continued its transformation programme during the period under review, which has been both costly and challenging for the business but I am pleased to see the progress that has been achieved to date. One of the key initiatives being undertaken has been outsourcing our custody and operational functions and, as previously reported, this complex project has run over budget and taken longer to implement. However, looking forward, it has resulted in a more robust and scalable operating platform from which to build the division.

QoI fungicides, which interfere with the pathogen’s respiratory chain by binding to the ubiquinol oxidation center (Qo) site of the cytochrome bc1 enzyme complex (complex III)8, have activity against virtually all oomycetes and fungal phytopathogens9. However, because QoIs affect a specific, single site, resistance to QoIs has rapidly developed in many pathogens. QoI resistance is largely due to a single amino acid substitution in the target cytochrome b protein (CYTB) of the pathogen. The main substitutions or changes are: glycine (G) to alanine (A) at position 143 (G143A), phenylalanine (F) to leucine (L) at position 129 (F129L), and glycine (G) to arginine (R) at position 137 (G137R)8,10. In most cases, the G143A mutation leads to high resistance11,12, while the F129L and the G137R mutations lead to moderate resistance9,13,14. Esser L et al.15 used crystallographic data of CYTB from bovin heart that was bound with different QoI inhibitors to explain how mutations in CYTB can reduce binding of QoI inhibitors and thereby result in resistance. In spite of this, how the shape of the QoI fungicide molecules conforms to the binding site on the mutants and how the point mutations affect fungicide binding are incompletely understood.

It is the RSE that indicates whether any point has a high deviation from the curve. It was observed that the %RSE and %RSD were quite similar for quantitation using linear and average response. The MDLs and IDOCs were processed using average response since the %RSD criteria were met for both Method 624.1 and 8260B/C. The DOC recovery and RPD limits were met for the compounds listed in Table 6 of Method 624.1, while for the remainder of the compounds the interim criteria of 30% RPD and 60-140% recovery were easily met. The MDLs also met 40 CFR Part 136 rules for acceptance. The MDL spike level was found to be greater than the quantified MDL, and the ratio of spiked amount to the quantified MDL was observed to be less than 10. Refer Table 2 for results.

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We fabricated polyacrylamide (PA) hydrogels and modified the hydrogel surface chemistry by treatment with hydrazine hydrate, and soft lithography was used to conjugate matrix proteins in various patterns on the surface (fig. S1) (36). Because we have previously shown that the effect of matrix stiffness on the MIC phenotype was negligible compared to interfacial effects (15), the Young’s modulus of gels was fixed at 10 kPa. As a model system, we selected the murine B16 melanoma cells (B16F0s) and used a representative putative MIC molecular marker, CD271. To assess whether MIC phenotypes enriched at perimeter features might influence the process of vessel formation of endothelial cells, we selected a spiral pattern with evolving perimeter curvatures that we showed previously would enrich a putative CD271+ MIC (15). B16F0s were grown on spiral-patterned PA gels, nonpatterned PA gels, and glass substrates for 5 days. Following culture, conditioned medium from B16F0s in different conditions was collected and added to human microvascular endothelial cells (hMVECs) in three-dimensional (3D) Matrigel culture. After 8 hours, hMVECs were fixed and the degree of tubulogenesis was imaged, and the tube areas were analyzed after normalizing cell number across conditions. Relative cell numbers were obtained after culturing B16F0s for 5 days in different geometries, nonpatterned substrates, or glass controls by counting cells in each condition from 12 identical substrates (fig. S2). First, we compared the tube formation of hMVECs with conditioned medium from spiral-patterned B16F0s or control medium, such as positive control containing an empirically derived cocktail of angiogenic growth factors, negative control containing regular endothelial cell growth medium (EGM), or normal B16F0 medium. Unlike the tube formation of hMVECs cultured in regular EGM (negative control), those cultured in the same medium with supplemented growth factors (positive control) had significantly higher (approximately twofold) tube formation (fig. S3). Tubulogenesis with conditioned medium collected from B16F0s cultured on spiral-patterned gels exhibited a more elongated morphology and higher hMVEC tube area relative to that with conditioned medium collected from B16F0s cultured on nonpatterned gels and glass substrates. Conditions that promoted the highest expression of CD271 in tumor cells also led to the highest degree of hMVEC tubulogenesis (R2 = 0.99; Fig. 1A). Because the conditioned medium from the B16F0s promoted endothelial tube formation in Matrigel, we next cocultured B16F0s and hMVECs in Matrigel to investigate direct heterotypic interactions between the cell populations. B16F0s cultured on spiral-patterned or nonpatterned PA gels for 5 days were trypsinized, and the same number of cells was recultured with hMVECs in Matrigel for 8 hours without conditioned medium. A similar trend was observed in the degree of tubulogenesis to that observed with conditioned medium (Fig. 1B). To deconstruct the effect of interfacial geometry on this enhancement of tubulogenesis, we used straight-line and ring geometries, where the curvature and perimeter/area ratio can be systematically varied. Curvature is inversely associated with the radius of shapes [line: infinite, large: 300 μm, medium: 150 μm, and small: 75 μm (radius of ring shapes was determined by outer circles)], and thus, curvatures of each shape are 0.0033, 0.0066, and 0.013 μm−1, respectively. Three different widths (20, 40, and 60 μm) represent different perimeter/area ratios (0.100, 0.050, and 0.033 μm−1, respectively). Curvature and perimeter/area terms are independent and increase with decreasing radius and width of shapes, respectively. B16F0s cultured in microconfinement with higher perimeter curvature and smaller width displayed higher expression of CD271 (Fig. 1C and fig. S4A). The degree of tubulogenesis with conditioned medium collected from B16F0s cultured on these straight-line and ring geometries (Fig. 1D and fig. S4B) corresponds to the expression of the CD271 marker. To investigate the relation between the degree of tubulogenesis and the expression of the MIC marker CD271, we obtained the Pearson correlation coefficient, which is the covariance of the two variables divided by the value of their SDs. When the correlation between tubulogenesis and expression of CD271 is analyzed with shape widths, cells cultured in 20-μm-wide shapes show the highest correlation (~0.94) relative to those cultured on wider shapes (40 μm, 0.77; 60 μm, 0.91) (Fig. 1E). In addition, when cocultured with hMVECs in Matrigel, B16F0s cultured on small (20-μm-wide) ring shapes displayed higher tubulogenesis than those cultured on 60-μm-wide ring shapes (fig. S5).

NPR: Many Apps Promise To Put You To Sleep, Some Help Curb Insomnia Paige Thesing has struggled with insomnia since high school. "It takes me a really long time to fall asleep — about four hours," she says. For years, her mornings were groggy and involved a "lot of coffee." After a year of trying sleep medication prescribed by her doctor, she turned to the internet for alternate solutions. About four months ago, she settled on a mobile phone meditation app called INSCAPE. (Chatterjee, 10/8)

By Junmin Lee, Amr A. Abdeen, Jamila Hedhli, Kathryn L. Wycislo, Iwona T. Dobrucki, Timothy M. Fan, Lawrence W. Dobrucki, Kristopher A. Kilian

Tagged with: 3d printing china • Beijing Huitianwei Technology Company Ltd • china • chinese 3d printers • Guorui Zhao • Hongqiang Zhang • HORI • HORI 3D printers

Growth factors (GFs) are powerful signaling molecules with the potential to drive regenerative strategies, including bone repair and vascularization. However, GFs are typically delivered in soluble format at supraphysiological doses because of rapid clearance and limited therapeutic impact. These high doses have serious side effects and are expensive. Although it is well established that GF interactions with extracellular matrix proteins such as fibronectin control GF presentation and activity, a translation-ready approach to unlocking GF potential has not been realized. We demonstrate a simple, robust, and controlled material-based approach to enhance the activity of GFs during tissue healing. The underlying mechanism is based on spontaneous fibrillar organization of fibronectin driven by adsorption onto the polymer poly(ethyl acrylate). Fibrillar fibronectin on this polymer, but not a globular conformation obtained on control polymers, promotes synergistic presentation of integrin-binding sites and bound bone morphogenetic protein 2 (BMP-2), which enhances mesenchymal stem cell osteogenesis in vitro and drives full regeneration of a nonhealing bone defect in vivo at low GF concentrations. This simple and translatable technology could unlock the full regenerative potential of GF therapies while improving safety and cost-effectiveness.

Just a couple of the projects under his leadership include utilising nanomaterials to convert carbon dioxide into clean fuel with only sunlight and water, value adding products through catalytic pathway, utilising nanoporous architectures for developing next generation energy storage and conversion devices, and the selective removal of cancer causing molecules.

Robust growth indicators for insecticides, pesticides, fertilizers and other agrochemicals have intensified the need to inert packaging materials. Polyvinyl alcohol films market adoption as a packaging material for agrochemicals is expected to drive growth during the forecast period.

The regulatory framework necessary to produce complex materials in this fashion will need thorough attention; indeed, our approach would require a completely new system for the regulation of API manufacture. This system would have to be developed alongside the evolution of this approach as a method for pharmaceutical synthesis, which we have presented here in proof- of-concept form; however, we can envision a situation in which regulatory agencies certify specific cartridge or module designs as soon as a digitized process is fully established (including the embedded quality-control protocols.