Technologies to address antimicrobial resistance Baker, Stephen J.; Payne, David J.; Rappuoli, Rino ...
Proceedings of the National Academy of Sciences - PNAS,
12/2018, Letnik:
115, Številka:
51
Journal Article
Recenzirano
Odprti dostop
Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that ...the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition.
High-Power Fiber Lasers Nilsson, Johan; Payne, David N.
Science (American Association for the Advancement of Science),
05/2011, Letnik:
332, Številka:
6032
Journal Article
Recenzirano
The brightness, robustness, and flexibility of high-power fiber laser sources provide an enabling technology for science and industry.
Lasers are used in a wide range of applications that benefit ...from the pinsharp (spatially coherent) beam and immense pulse peak power they can provide. In many cases, notably manufacturing, high average power is essential for cutting, welding, and drilling. The low-power optical fiber amplifier (
1
), acclaimed as the mainstay of the fiber-based Internet, can be massively scaled to emerge as an industrial laser frontrunner, reaching an output power of >1 kW (
2
) and, more recently, an astounding 10 kW (
3
). These results were obtained with (nearly) diffraction-limited beam quality, which determines the ability to focus to a tight spot. Together with the power and wavelength, it determines the spatial brightness, or radiance. The brightness is exceptionally high for these fiber lasers, and this, rather than the power itself, determines the power density achievable on a target.
While progress has been made in understanding the behaviour of the recently identified carrier-induced degradation mechanism in p-type multicrystalline silicon solar cells, little is currently known ...about the root cause of the defect or its possible existence in other materials. In this work, we present evidence suggesting that the defect also exists in Czochralski grown monocrystalline silicon wafers. For both mono- and multicrystalline silicon we demonstrate: 1) the presence of a degradation and recovery of bulk minority carrier lifetime induced by either illuminated or dark annealing; 2) a modulation in the magnitude of degradation by varying the firing conditions; and 3) capture cross-section ratios of 39.4 ± 4.9 and 33.4 ± 1.5 in monocrystalline and multicrystalline silicon, respectively. The results indicate that the recently identified degradation mechanism does not only occur in multicrystalline silicon from illuminated annealing at elevated temperatures, but it is also induced by dark annealing at elevated temperatures, and that the degradation can occur in Czochralski grown silicon.
•Identical carrier-induced degradation in mono- and multi-crystalline silicon materials.•Degradation and recovery cycle induced via a purely thermal route.•Defect activation and degradation mechanics have a dependency on firing conditions.•Shockley-Read-Hall statistics show similarities to defects formed under illumination.
The sequencing of the first complete bacterial genome in 1995 heralded a new era of hope for antibacterial drug discoverers, who now had the tools to search entire genomes for new antibacterial ...targets. Several companies, including GlaxoSmithKline, moved back into the antibacterials area and embraced a genomics-derived, target-based approach to screen for new classes of drugs with novel modes of action. Here, we share our experience of evaluating more than 300 genes and 70 high-throughput screening campaigns over a period of 7 years, and look at what we learned and how that has influenced GlaxoSmithKline's antibacterials strategy going forward.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The chemistry of post transition metals is dominated by the group oxidation state N and a lower N-2 oxidation state, which is associated with occupation of a metal s(2) lone pair, as found in ...compounds of Tl(I), Pb(II) and Bi(III). The preference of these cations for non-centrosymmetric coordination environments has previously been rationalised in terms of direct hybridisation of metal s and p valence orbitals, thus lowering the internal electronic energy of the N-2 ion. This explanation in terms of an on-site second-order Jahn-Teller effect remains the contemporary textbook explanation. In this tutorial review, we review recent progress in this area, based on quantum chemical calculations and X-ray spectroscopic measurements. This recent work has led to a revised model, which highlights the important role of covalent interaction with oxygen in mediating lone pair formation for metal oxides. The role of the anion p atomic orbital in chemical bonding is key to explaining why chalcogenides display a weaker preference for structural distortions in comparison to oxides and halides. The underlying chemical interactions are responsible for the unique physicochemical properties of oxides containing lone pairs and, in particular, to their application as photocatalysts (BiVO(4)), ferroelectrics (PbTiO(3)), multi-ferroics (BiFeO(3)) and p-type semiconductors (SnO). The exploration of lone pair systems remains a viable a venue for the design of functional multi-component oxide compounds.
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•Pd(0), In2O3 and PdIn intermetallic nanoparticles prepared and assessed.•PdIn intermetallic compound is highly active and selective for the liquid phase methanol synthesis from ...CO2.•70% higher methanol production rate than the reference Cu/ZnO/Al2O3 catalyst.•Surface In-enriched intermetallic PdIn nanoparticles (ca. 8nm) identified.•PdIn intermetallic compound shows improved stability.
Direct hydrogenation of CO2 to methanol could offer significant environmental benefits, if efficient catalysts can be developed. Here, bimetallic Pd-In nanoparticles show good performance as catalysts for this reaction. Unsupported nanoparticles are synthesised by the thermal decomposition of Pd(acetate)2 and In(acetate)3 precursors in a high boiling point solvent (squalane), followed by reduction using dilute H2 gas (210°C). Adjusting the ratio of the two metallic precursors allow access to 5–10nm nanoparticles with different phase compositions, including metallic Pd(0), In2O3 and intermetallic PdIn. Liquid phase methanol synthesis experiments (50bar, 210°C, H2:CO2=3:1) identify the intermetallic PdIn nanoparticles as the most efficient. The catalysts exhibit around 70% higher methanol rates (normalised to the overall molar metal content) compared to the conventional heterogeneous Cu/ZnO/Al2O3 catalyst (900 and 540μmolmmolPdInorCuZnAl−1h−1, respectively). In addition, the optimum Pd/In catalyst shows an improved methanol selectivity over the whole temperature range studied (190–270°C), reaching >80% selectivity at 270°C, compared to only 45% for the reference Cu/ZnO/Al2O3 catalyst. Experiments showed an improvement in stability; the methanol production rate declined by 20% after 120h run for the optimum PdIn-based compared with 30% for the Cu/ZnO/Al2O3 catalyst (after 25h). The optimum catalyst consists of ∼8nm nanoparticles comprising a surface In-enriched PdIn intermetallic phase as characterised by XRD, HR-TEM, STEM-EDX and XPS. Post-catalysis analysis of the optimum catalyst shows that the same PdIn bimetallic phase is retained with only a slight increase in the nanoparticle size.
Bimetallic catalysts combining precious and earth-abundant metals in well designed nanoparticle architectures can enable cost efficient and stable heterogeneous catalysis. Here, we present an ...interaction-driven in-situ approach to engineer finely dispersed Ni decorated Pt nanoparticles (1-6 nm) on perovskite nanofibres via reduction at high temperatures (600-800
C). Deposition of Pt (0.5 wt%) enhances the reducibility of the perovskite support and promotes the nucleation of Ni cations via metal-support interaction, thereafter the Ni species react with Pt forming alloy nanoparticles, with the combined processes yielding smaller nanoparticles that either of the contributing processes. Tuneable uniform Pt-Ni nanoparticles are produced on the perovskite surface, yielding reactivity and stability surpassing 1 wt.% Pt/γ-Al
O
catalysts for CO oxidation. This approach heralds the possibility of in-situ fabrication of supported bimetallic nanoparticles with engineered compositional distributions and performance.
In the past decade nanowires have attracted an increase interest because of their extraordinary mechanical strength. In fact, material properties in the nanoregime are extremely different from those ...found in macroscopic samples: few crystalline materials have shown a tensile strength in excess of 10 GPa in the form of nanowires. Still the length of defect-free crystalline nanowires is limited to a few millimeters and the strength of long nanowires is compromised by defects. The strength of glass nanowires is less affected by single defects. In this paper we present the ultimate strength of glass silica nanowires manufactured by a top-down fabrication technique; this is the highest value reported for glass materials. The measured ultimate strength is in excess of 10 GPa and increases for decreasing nanowire diameters. Scanning electron micrographs of the broken fragments showed a fragile rupture.
Summary
Persistent staphylococcal infections often involve surface‐associated communities called biofilms. Staphylococcus aureus biofilm development is mediated by the co‐ordinated production of the ...biofilm matrix, which can be composed of polysaccharides, extracellular DNA (eDNA) and proteins including amyloid fibers. The nature of the interactions between matrix components, and how these interactions contribute to the formation of matrix, remain unclear. Here we show that the presence of eDNA in S. aureus biofilms promotes the formation of amyloid fibers. Conditions or mutants that do not generate eDNA result in lack of amyloids during biofilm growth despite the amyloidogeneic subunits, phenol soluble modulin peptides, being produced. In vitro studies revealed that the presence of DNA promotes amyloid formation by PSM peptides. Thus, this work exposes a previously unacknowledged interaction between biofilm matrix components that furthers our understanding of functional amyloid formation and S. aureus biofilm biology.
Amyloids are remarkably stable protein polymers that form β‐sheet rich fibers. In the past amyloids were considered solely the result of protein misfolding and associated with many human diseases. However, recent research has revealed many microbes have capitalized on the amyloid fold and utilize amyloids for such functions as reinforcing biofilms and storing toxins. This work reveals how S. aureus controls the formation of amyloids and how these fibers interact with other biofilm matrix components.
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