Characterisation of Human Embryonic Stem Cells Conditioning Media by 1H-Nuclear Magnetic Resonance Spectroscopy

BACKGROUND: Cell culture media conditioned by human foreskin fibroblasts (HFFs) provide a complex supplement of protein and metabolic factors that support in vitro proliferation of human embryonic stem cells (hESCs). However, the conditioning process is variable with different media batches often exhibiting differing capacities to maintain hESCs in culture. While recent studies have examined the protein complement of conditioned culture media, detailed information regarding the metabolic component of this media is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Using a (1)H-Nuclear Magnetic Resonance ((1)H-NMR) metabonomics approach, 32 metabolites and small compounds were identified and quantified in media conditioned by passage 11 HFFs (CMp11). A number of metabolites were secreted by HFFs with significantly higher concentration of lactate, alanine, and formate detected in CMp11 compared to non-conditioned media. In contrast, levels of tryptophan, folate and niacinamide were depleted in CMp11 indicating the utilisation of these metabolites by HFFs. Multivariate statistical analysis of the (1)H-NMR data revealed marked age-related differences in the metabolic profile of CMp11 collected from HFFs every 24 h over 72 h. Additionally, the metabolic profile of CMp11 was altered following freezing at -20°C for 2 weeks. CM derived from passage 18 HFFs (CMp18) was found to be ineffective at supporting hESCs in an undifferentiated state beyond 5 days culture. Multivariate statistical comparison of CMp11 and CMp18 metabolic profiles enabled rapid and clear discrimination between the two media with CMp18 containing lower concentrations of lactate and alanine as well as higher concentrations of glucose and glutamine. CONCLUSIONS/SIGNIFICANCE: (1)H-NMR-based metabonomics offers a rapid and accurate method of characterising hESC conditioning media and is a valuable tool for monitoring, controlling and optimising hESC culture media preparation

In Search of the Optimal Surgical Treatment for Velopharyngeal Dysfunction in 22q11.2 Deletion Syndrome: A Systematic Review

<div><h3>Background</h3><p>Patients with the 22q11.2 deletion syndrome (22qDS) and velopharyngeal dysfunction (VPD) tend to have residual VPD following surgery. This systematic review seeks to determine whether a particular surgical procedure results in superior speech outcome or less morbidity.</p> <h3>Methodology/ Principal Findings</h3><p>A combined computerized and hand-search yielded 70 studies, of which 27 were deemed relevant for this review, reporting on a total of 525 patients with 22qDS and VPD undergoing surgery for VPD. All studies were levels 2c or 4 evidence. The methodological quality of these studies was assessed using criteria based on the Cochrane Collaboration's tool for assessing risk of bias. Heterogeneous groups of patients were reported on in the studies. The surgical procedure was often tailored to findings on preoperative imaging. Overall, 50% of patients attained normal resonance, 48% attained normal nasal emissions scores, and 83% had understandable speech postoperatively. However, 5% became hyponasal, 1% had obstructive sleep apnea (OSA), and 17% required further surgery. There were no significant differences in speech outcome between patients who underwent a fat injection, Furlow or intravelar veloplasty, pharyngeal flap pharyngoplasty, Honig pharyngoplasty, or sphincter pharyngoplasty or Hynes procedures. There was a trend that a lower percentage of patients attained normal resonance after a fat injection or palatoplasty than after the more obstructive pharyngoplasties (11–18% versus 44–62%, p = 0.08). Only patients who underwent pharyngeal flaps or sphincter pharyngoplasties incurred OSA, yet this was not statistically significantly more often than after other procedures (p = 0.25). More patients who underwent a palatoplasty needed further surgery than those who underwent a pharyngoplasty (50% versus 7–13%, p = 0.03).</p> <h3>Conclusions/ Significance</h3><p>In the heterogeneous group of patients with 22qDS and VPD, a grade C recommendation can be made to minimize the morbidity of further surgery by choosing to perform a pharyngoplasty directly instead of only a palatoplasty.</p> </div

Direct measurement of thermal conductivity in solid iron at planetary core conditions

The conduction of heat through minerals and melts at extreme pressures and temperatures is of central importance to the evolution and dynamics of planets. In the cooling Earth’s core, the thermal conductivity of iron alloys defines the adiabatic heat flux and therefore the thermal and compositional energy available to support the production of Earth’s magnetic field via dynamo action1, 2, 3. Attempts to describe thermal transport in Earth’s core have been problematic, with predictions of high thermal conductivity4, 5, 6, 7 at odds with traditional geophysical models and direct evidence for a primordial magnetic field in the rock record8, 9, 10. Measurements of core heat transport are needed to resolve this difference. Here we present direct measurements of the thermal conductivity of solid iron at pressure and temperature conditions relevant to the cores of Mercury-sized to Earth-sized planets, using a dynamically laser-heated diamond-anvil cell11, 12. Our measurements place the thermal conductivity of Earth’s core near the low end of previous estimates, at 18–44 watts per metre per kelvin. The result is in agreement with palaeomagnetic measurements10 indicating that Earth’s geodynamo has persisted since the beginning of Earth’s history, and allows for a solid inner core as old as the dynamo

States of being: art and identity in digital space and time

This one-day Symposium explored themes of personhood, modernity and digital art, bringing together speakers from a range of disciplines to consider technology, artistic practice and society. It seeks a renewed consideration of the role of art in illuminating human identity in a positive relation with technology, and its transformative effects upon space and time. The concerns for the role of art amidst the forces of a post-modern world are influenced by important legacies of the past, by which ideas about human identity and difference have been made meaningful in the relation of history and technology. In the frequently transient and conflicting forces of humanness and forces of modernity, the digital world of the arts emerges as a means by which new ideas of space and time can be considered, with new perspectives of human identity seen as states of being, towards the possibilities of experience, technology, individuality and society

Computing Teachers' Perspectives on Threshold Concepts: Functions and Procedural Abstraction

With the introduction of the new computing curriculum in England, teachers are facing many challenges, among them the teaching of computer programming. Literature suggests that the conceptual understanding of this subject contributes to its difficulty and that threshold concepts, as a source of troublesome knowledge, have a significant role in this. This paper explores computing teachers' perspectives on the Threshold Concept framework and suggests potential threshold concepts in the area of Functions and, more generally, in Procedural Abstraction. A study was conducted, using the Delphi method, including both computing teachers with experience teaching at upper secondary/high school and computing teachers with experience practicing programming in a professional environment for more than 7 years. The results indicate that the majority of the participants support that the Threshold Concept framework can explain students' difficulties in programming and agreed on 11 potential threshold concepts in the area of Functions and Procedural Abstraction. The participants focused more on the troublesome characteristic of threshold concepts and less on the transformative and integrative. Most of the participants also specified that they would change the way they teach a concept if they knew that this is a threshold one. Finally, the paper discusses the findings and how these will shape our future research

Pulsed power accelerator for material physics experiments

We have developed the design of Thor: a pulsed power accelerator that delivers a precisely shaped current pulse with a peak value as high as 7 MA to a strip-line load. The peak magnetic pressure achieved within a 1-cm-wide load is as high as 100 GPa. Thor is powered by as many as 288 decoupled and transit-time isolated bricks. Each brick consists of a single switch and two capacitors connected electrically in series. The bricks can be individually triggered to achieve a high degree of current pulse tailoring. Because the accelerator is impedance matched throughout, capacitor energy is delivered to the strip-line load with an efficiency as high as 50%. We used an iterative finite element method (FEM), circuit, and magnetohydrodynamic simulations to develop an optimized accelerator design. When powered by 96 bricks, Thor delivers as much as 4.1 MA to a load, and achieves peak magnetic pressures as high as 65 GPa. When powered by 288 bricks, Thor delivers as much as 6.9 MA to a load, and achieves magnetic pressures as high as 170 GPa. We have developed an algebraic calculational procedure that uses the single brick basis function to determine the brick-triggering sequence necessary to generate a highly tailored current pulse time history for shockless loading of samples. Thor will drive a wide variety of magnetically driven shockless ramp compression, shockless flyer plate, shock-ramp, equation of state, material strength, phase transition, and other advanced material physics experiments