We investigated synthesis and electrocatalytic performance of metal-free, nitrogen-doped carbon nano-onions (N-CNOs) for oxygen reduction reactions in alkaline electrolyte. N-CNOs were prepared by ...chemical oxidation of nanodiamond-derived carbon nano-onions (ox-CNOs), followed by thermal annealing with urea under the flow of argon gas. The chemical oxidation step was critical to successfully internalize nitrogen atoms into carbon network. Morphology, microstructure, and chemical states of carbon nano-onions (CNOs), ox-CNOs, and N-CNOs were characterized by transmission electron microscopy (TEM), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS). Electrocatalytic activity of pristine and modified CNOs was characterized by a series of electrochemical measurements. Electrochemical characterizations were done with thin film electrodes of CNOs mounted on a glassy carbon disk. Compared to CNOs and ox-CNOs, N-CNOs showed remarkably enhanced electron-transfer kinetics with the 4-electron transfer as a dominant reaction pathway. Overall, N-CNOs exhibited electrochemical characteristics comparable to commercial Pt/C catalysts.
There are an ever‐increasing number of biopharmaceutical candidates in clinical trials fueling an urgent need to streamline the cell line development process. A critical part of the process is the ...methodology used to generate and screen candidate cell lines compatible with GMP manufacturing processes. The relatively large amount of clone phenotypic variation observed from conventional “random integration” (RI)‐based cell line construction is thought to be the result of a combination of the position variegation effect, genome plasticity and clonal variation. Site‐specific integration (SSI) has been used by several groups to temper the influence of the position variegation effect and thus reduce variability in expression of biopharmaceutical candidates. Following on from our previous reports on the application of the Fer1L4 locus for SSI in CHOK1SV (10E9), we have combined this locus and a CHOK1SV glutamine synthetase knockout (GS‐KO) host to create an improved expression system. The host, CHOK1SV GS‐KO SSI (HD7876), was created by homology directed integration of a targetable landing pad flanked with incompatible Frt sequences in the Fer1L4 gene. The targeting vector contains a promoterless GS expression cassette and monoclonal antibody (mAb) expression cassettes, flanked by Frt sites compatible with equivalent sites flanking the landing pad in the host cell line. SSI clones expressing four antibody candidates, selected in a streamlined cell line development process, have mAb titers which rival RI (1.0–4.5 g/L) and robust expression stability (100% of clones stable through the 50 generation “manufacturing window” which supports commercial manufacturing at 12,000 L bioreactor scale).
Accretion onto the Supermassive Black Hole in M87 Di Matteo, Tiziana; Allen, Steven W; Fabian, Andrew C ...
Astrophysical journal/The Astrophysical journal,
01/2003, Letnik:
582, Številka:
1
Journal Article
The emergence of spatial organisation in biofilm growth is one of the most fundamental topics in biofilm biophysics and microbiology. It has long been known that growing biofilms can adopt smooth or ...rough interface morphologies, depending on the balance between nutrient supply and microbial growth; this 'fingering' transition has been linked with the average width of the 'active layer' of growing cells at the biofilm interface. Here we use long-time individual-based simulations of growing biofilms to investigate in detail the driving factors behind the biofilm-fingering transition. We show that the transition is associated with dynamical changes in the active layer. Fingering happens when gaps form in the active layer, which can cause local parts of the biofilm interface to pin, or become stationary relative to the moving front. Pinning can be transient or permanent, leading to different biofilm morphologies. By constructing a phase diagram for the transition, we show that the controlling factor is the magnitude of the relative fluctuations in the active layer thickness, rather than the active layer thickness per se. Taken together, our work suggests a central role for active layer dynamics in controlling the pinning of the biofilm interface and hence biofilm morphology.
A scalable and cost‐effective synthetic polymer substrate that supports robust expansion and subsequent multilineage differentiation of human pluripotent stem cells (hPSCs) with defined commercial ...media is presented. This substrate can be applied to common cultureware and used off‐the‐shelf after long‐term storage. Expansion and differentiation of hPSCs are performed entirely on the polymeric surface, enabling the clinical potential of hPSC‐derived cells to be realized.
Increasing diversity amongst surgeons results in a wide range of sizes and strengths. There are many types of biases affecting women surgeons. This study evaluates what challenges women surgeons may ...have with surgical equipment.
An online survey was distributed to Women in Surgery social media groups in North America and Australasia between April 2022-July 2022.
There were 480 respondents across the range of specialties. 453 surgeons were included. Median glove size was 6.5. Difficulty with use of surgical instruments due to size was reported by 89% of surgeons and 71% reported difficulty due to the required grip strength. One hundred and twelve different tools were reported to be problematic.
This study highlights a potential source of androcentric bias which could be addressed to improve equity for women surgeons.
This study considers optimizing the planform of wind turbine blades to ultimately enhance wind plant controls, namely, wake steering strategies. Adjoint‐enabled unsteady actuator line simulations are ...carried out to obtain gradients for optimization of several different performance objectives with respect to blade chord length at 10 locations along blade span. We demonstrate different blade design optimizations that can maximize time‐averaged lateral wake deflection, entrainment of kinetic energy, or total power of multiple turbines. Our optimized designs can produce a 4+% increase in wake deflection, a 4× increase in vertical kinetic energy entrainment, or a 3.6% increase in power when compared with the baseline case. While lateral wake deflection is only modestly sensitive to chord changes, we find that increasing the outboard chord length can dramatically increase kinetic energy entrainment, resulting in faster wake recovery and gains in net power. While this work develops only a few case studies emphasizing relative performance improvements and general trends, these results show the promise of a framework that combines mid‐fidelity computation with adjoint‐based optimization for control and design problems.
X-ray crystallography at X-ray free-electron laser sources is a powerful method for studying macromolecules at biologically relevant temperatures. Moreover, when combined with complementary ...techniques like X-ray emission spectroscopy, both global structures and chemical properties of metalloenzymes can be obtained concurrently, providing insights into the interplay between the protein structure and dynamics and the chemistry at an active site. The implementation of such a multimodal approach can be compromised by conflicting requirements to optimize each individual method. In particular, the method used for sample delivery greatly affects the data quality. We present here a robust way of delivering controlled sample amounts on demand using acoustic droplet ejection coupled with a conveyor belt drive that is optimized for crystallography and spectroscopy measurements of photochemical and chemical reactions over a wide range of time scales. Studies with photosystem II, the phytochrome photoreceptor, and ribonucleotide reductase R2 illustrate the power and versatility of this method.
Inhibition of proliferation in estrogen receptor-positive (ER
) breast cancers after short-term antiestrogen therapy correlates with long-term patient outcome. We profiled 155 ER
/human epidermal ...growth factor receptor 2-negative (HER2
) early breast cancers from 143 patients treated with the aromatase inhibitor letrozole for 10 to 21 days before surgery. Twenty-one percent of tumors remained highly proliferative, suggesting that these tumors harbor alterations associated with intrinsic endocrine therapy resistance. Whole-exome sequencing revealed a correlation between 8p11-12 and 11q13 gene amplifications, including
and
, respectively, and high Ki67. We corroborated these findings in a separate cohort of serial pretreatment, postneoadjuvant chemotherapy, and recurrent ER
tumors. Combined inhibition of FGFR1 and CDK4/6 reversed antiestrogen resistance in ER
/
coamplified CAMA1 breast cancer cells. RNA sequencing of letrozole-treated tumors revealed the existence of intrachromosomal
fusion transcripts and increased expression of gene signatures indicative of enhanced E2F-mediated transcription and cell cycle processes in cancers with high Ki67. These data suggest that short-term preoperative estrogen deprivation followed by genomic profiling can be used to identify druggable alterations that may cause intrinsic endocrine therapy resistance.
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