Explosivity : an unusual challenge in drug development

There remains an urgent global need for new drugs to combat diseases such as malaria, tuberculosis and cancer, as well as overcoming increasing antibiotic resistance. Chemists are moving into ‘new chemical space’ for drug design (1,2) and with this comes the possibility of traditional (and stable) ‘carbon-carbon’ bond structures being replaced by more ‘exotic’ bonding arrangements. While the implication of this on pharmaceutical stability can often be mitigated by suitable formulation and storage strategies, we came across an unusual case of chemical stability: the possibility that the drug was an explosive! By pushing drug designing into uncharted chemical space it could be argued that the possibility of finding explosive molecules of pharmaceutical interest will increase

Bypassing the proline/thiazoline requirement of the macrocyclase PatG

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Developing sexual competence? Exploring strategies for the provision of effective sexualities and relationships education

School-based sexualities and relationships education (SRE) offers one of the most promising means of improving young people's sexual health through developing 'sexual competence'. In the absence of evidence on whether the term holds the same meanings for young people and adults (e.g. teachers, researchers, policy-makers), the paper explores 'adult' notions of sexual competence as construed in research data and alluded to in UK Government guidance on SRE, then draws on empirical research with young people on factors that affect the contexts, motivations and outcomes of sexual encounters, and therefore have implications for sexual competence. These data from young people also challenge more traditional approaches to sexualities education in highlighting disjunctions between the content of school-based input and their reported sexual experience. The paper concludes by considering the implications of these insights for developing a shared notion of what SRE is trying to achieve and suggestions for recognition in the content and approaches to SRE.</p

Integrated processing of sugarcane bagasse : arabinoxylan extraction integrated with ethanol production.

The authors gratefully acknowledge the funding for “Project POC02_NOV 14 Campbell” from the Lignocellulosic Biorefinery Network (LBNet), funded by the Biotechnology and Biological Sciences Research Council (BBSRC).A proof-of-concept project compared extraction of arabinoxylans (AX) from sugarcane bagasse and wheat bran via alkaline hydrogen peroxide followed by enzyme-assisted extraction with combinations of feruloyl esterases and a xylanase. Bagasse contains comparable amounts of AX to wheat bran, but with a much lower arabinoxylan substitution on the xylan backbone (A:X ratio of around 0.2 compared with 0.6 for wheat bran), hence offering AX products with distinctive functionality and potential end uses. In the current work, bagasse released its AX more readily than wheat bran, and released a wider range of molecular weights. Use of feruloyl esterase and xylanase enzymes on their own or following alkaline peroxide extraction did not enhance AX release substantially; however, the xylanase appeared to be effective at reducing the size of AX molecules, and there is scope to optimise the effects of enzymes to produce specific AX product fractions. As bagasse frequently arises within the context of bioethanol production, integration of AX extraction with ethanol production could allow economic production of a portfolio of AX products, as has been demonstrated in principle for AX co-production in a wheat ethanol plant.PostprintPeer reviewe

\u3ci\u3eMedicine Meets Virtual Reality 15\u3c/i\u3e

Chapter, Virtual Reality for Robotic Laparoscopic Surgical Training, co-authored by Nicholas Stergiou, UNO faculty member. Our culture is obsessed with design. Sometimes designers can fuse utility and fantasy to make the mundane appear fresh—a cosmetic repackaging of the same old thing. Because of this, medicine—grounded in the unforgiving realities of the scientific method and peer review, and of flesh, blood, and pain—can sometimes confuse “design” with mere “prettifying.” Design solves real problems, however. This collection of papers underwrites the importance of design for the MMVR community, within three different environments: in vivo, in vitro and in silico. in vivo: we design machines to explore our living bodies. Imaging devices, robots, and sensors move constantly inward, operating within smaller dimensions: system, organ, cell, DNA. in vitro: Using test tubes and Petri dishes, we isolate in vivo to better manipulate and measure biological conditions and reactions. in silico: We step out of the controlled in vitro environment and into a virtual reality. The silica mini-worlds of test tubes and Petri dishes are translated into mini-worlds contained within silicon chips. The future of medicine remains within all three environments: in vivo, in vitro, and in silico. Design is what makes these pieces fit together—the biological, the informational, the physical/material—into something new and more useful.https://digitalcommons.unomaha.edu/facultybooks/1235/thumbnail.jp

Rotationally resolved photoelectron spectra in resonance enhanced multiphoton ionization of Rydberg states of NH

Results of combined theoretical and experimental studies of photoelectron spectra resulting from (2+1) resonance enhanced multiphoton ionization (REMPI) via the f ^1Π(3pσ), g ^1Δ(3pπ), and h ^1Σ^+(3pπ) Rydberg states of NH are reported. The overall agreement between these calculated and measured spectra is encouraging. Strong ΔN=N+−N’=even peaks, particularly for ΔN=0, are observed in these spectra. Low‐energy Cooper minima are predicted to occur in the l=2 wave of the kπ(^1Σ^+), kπ(^1Σ^−), and kπ(^1Δ) photoelectron channels for the f state, the kπ(^1Δ), kδ(^1Π), and kδ(^1Φ) channels for the g state, and the kπ(^1Σ^+) and kδ(^1Π) channels for the h state of NH. Depletion of the d wave (l=2) contributions to the photoelectron matrix element in the vicinity of these Cooper minima subsequently enhances the relative importance of the odd l  waves. The observed ΔN transitions are also affected by strong l  mixing in the electronic continuum induced by the nonspherical molecular potential. Interference of continuum waves between degenerate ionization channels also determines the spectral pattern observed for photoionization of the f ^1Π state of NH. Photoelectron angular distributions and the angular momentum compositions of photoelectron matrix elements provide further insight into the origin of these Cooper minima

Total synthesis and biological evaluation of the tetramic acid based natural product harzianic acid and its stereoisomers

Financial support for this project was provided by Cancer Research UK (Grant No. C21383/A6950)The bioactive natural product harzianic acid was prepared for the first time in just six steps (longest linear sequence) with an overall yield of 22%. The identification of conditions to telescope amide bond formation and a Lacey-Dieckmann reaction into one pot proved important. The three stereoisomers of harzianic acid were also prepared, providing material for comparison of their biological activity. While all of the isomers promoted root growth, improved antifungal activity was unexpectedly associated with isomers in the enantiomeric series opposite that of harzianic acid.Publisher PDFPeer reviewe

KRAS mutation testing of tumours in adults with metastatic colorectal cancer: a systematic review and cost-effectiveness analysis

__Abstract__ Background: Bowel cancer is the third most common cancer in the UK. Most bowel cancers are initially treated with surgery, but around 17% spread to the liver. When this happens, sometimes the liver tumour can be treated surgically, or chemotherapy may be used to shrink the tumour to make surgery possible. Kirsten rat sarcoma viral oncogene (KRAS) mutations make some tumours less responsive to treatment with biological therapies such as cetuximab. There are a variety of tests available to detect these mutations. These vary in the specific mutations that they detect, the amount of mutation they detect, the amount of tumour cells needed, the time to give a result, the error rate and cost. Objectives: To compare the performance and cost-effectiveness of KRAS mutation tests in differentiating adults with metastatic colorectal cancer whose metastases are confined to the liver and are unresectable and who may benefit from first-line treatment with cetuximab in combination with standard chemotherapy from those who should receive standard chemotherapy alone

Atomistic modelling of large-scale metal film growth fronts

We present simulations of metallization morphologies under ionized sputter deposition conditions, obtained by a new theoretical approach. By means of molecular dynamics simulations using a carefully designed interaction potential, we analyze the surface adsorption, reflection, and etching reactions taking place during Al physical vapor deposition, and calculate their relative probability. These probabilities are then employed in a feature-scale cellular-automaton simulator, which produces calculated film morphologies in excellent agreement with scanning-electron-microscopy data on ionized sputter deposition.Comment: RevTeX 4 pages, 2 figure