Early stages of phase selection in MOF formation observed in molecular Monte Carlo simulations

Metal-organic frameworks (MOF) comprising metal nodes bridged by organic linkers show great promise because of their guest-specific gas sorption, separation, drug-delivery, and catalytic properties. The selection of metal node, organic linker, and synthesis conditions in principle offers engineered control over both structure and function. For MOFs to realise their potential and to become more than just promising materials, a degree of predictability in the synthesis and a better understanding of the self-assembly or initial growth processes is of paramount importance. Using cobalt succinate, a MOF that exhibits a variety of phases depending on synthesis temperature and ligand to metal ratio, as proof of concept, we present a molecular Monte Carlo approach that allows us to simulate the early stage of MOF assembly. We introduce a new Contact Cluster Monte Carlo (CCMC) algorithm which uses a system of overlapping "virtual sites" to represent the coordination environment of the cobalt and both metal-metal and metal-ligand associations. Our simulations capture the experimentally observed synthesis phase distinction in cobalt succinate at 348 K. To the best of our knowledge this is the first case in which the formation of different MOF phases as a function of composition is captured by unbiased molecular simulations. The CCMC algorithm is equally applicable to any system in which short-range attractive interactions are a dominant feature, including hydrogen-bonding networks, metal-ligand coordination networks, or the assembly of particles with "sticky" patches, such as colloidal systems or the formation of protein complexes.</p

Can sector specific REIT strategies outperform a diversified benchmark?

Purpose: We investigate the performance of different portfolios of REITs which specialise by property type compared to the performance of a diversified free-float market capitalisation weighted benchmark index to determine whether superior risk-adjusted returns can be achieved.. Design/methodology/approach: Firstly we examine the performance of portfolios constructed using the criteria of Equal Weight, Minimum Variance, Maximum Sharpe and Risk Parity rather than free-float market capitalisation. Secondly we apply an automated trading strategy of Trend Following to see if this filter will improve risk-adjusted returns. Findings: The two step process of forming combinations of REIT sectors with the subsequent addition of a trend following overlay can offer clear benefits relative to a passive benchmark investment. Research limitations/implications: Although three of the four strategies were shown to outperform the benchmark index on a risk-adjusted basis, one issue was that the efficient portfolios tended to have large weightings to relatively few sectors. We also found that maximum drawdowns (losses) of the strategies tended to be rather high, as was the benchmark Practical implications: The methods outlined in this paper can be applied to construct superior risk-adjusted REIT portfolios globally. Originality/value: Although studies have been undertaken separately on REIT specialisation, and Trend Following in equity and commodity markets this paper is the first to combines the two topics, and therefore has particular value for real estate fund managers globally

Poly(acrylic acid) interpolymer complexes

YesInterpolymer complex formation of poly(acrylic acid) with other macromolecules can occur via several mechanisms that vary depending on the pH. At low pH the protonated acid functional group can form bonds with both donor and acceptor moieties, resulting in desolvated structures consisting of two polymers. Complexes were formed in dilute solutions of PAA, functionalised with acenaphthylene, with a range of other polymers including: poly(NIPAM); poly(ethylene oxide) (PEO); poly(dimethylacrylamide) (PDMA); poly(diethyl acrylamide) (PDEAM) poly(vinyl alcohol) (PVA) and poly(vinyl pyrolidinone) (PVP). Fluorescence anisotropy was used to demonstrate complex formation in each case by monitoring the reductions in segmental motion of the chain as the complexes formed. Considerations of the molecular structures of the complexing moieties suggest that solvation energies and pKas play an important role in complex formation

Differences in access to Emergency Paediatric Intensive Care and care during Transport (DEPICT): study protocol for a mixed methods study.

INTRODUCTION: Following centralisation of UK paediatric intensive care, specialist retrieval teams were established who travel to general hospitals to stabilise and transport sick children to regional paediatric intensive care units (PICUs). There is national variation among these PICU retrieval teams (PICRTs) in terms of how quickly they reach the patient's bedside and in the care provided during transport. The impact of these variations on clinical outcomes and the experience of stakeholders (patients, families and healthcare staff) is however unknown. The primary objective of this study is to address this evidence gap. METHODS AND ANALYSIS: This mixed-methods project involves the following: (1) retrospective analysis of linked data from routine clinical audits (2014-2016) to assess the impact of service variations on 30-day mortality and other secondary clinical outcomes; (2) a prospective questionnaire study conducted at 24 PICUs and 9 associated PICRTs in England and Wales over a 12-month period in 2018 to collect experience data from parents of transported children as well as qualitative analysis of in-depth interviews with a purposive sample of patients, parents and staff to assess the impact of service variations on patient/family experience; (3) health economic evaluation analysing transport service costs (and other associated costs) against lives saved and longer term measurements of quality of life at 12 months in transported children and (4) mathematical modelling evaluating the costs and potential impact of different service configurations. A final work stream involves a series of stakeholder workshops to synthesise study findings and generate recommendations. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Health Research Authority, ref: 2 18 569. Study results will be actively disseminated through peer-reviewed journals, conference presentations, social media, print and broadcast media, the internet and stakeholder workshops

Studying the Galactic Bulge Through Spectroscopy of Microlensed Sources: I. Theoretical Considerations

The observed spectra of the microlensed sources towards the Galactic bulge may be used as a tool for studying the kinematics and extinction effects in the Galactic bulge. In this paper, we first investigate the expected distribution of the microlensed sources as a function of depth within the Galactic bulge. Our analysis takes a magnitude limited microlensing survey into account, and includes the effects of extinction. We show that, in the current magnitude limited surveys, the probability that the source lies at the far side of the bulge is larger than the probability that the source lies at the near side. We then investigate the effects of extinction on the observed spectra of microlensed sources. Kurucz model spectra and the observed extinctions towards the Galactic bulge have been used to demonstrate that the microlensed sources should clearly show the effects of extinction which, in turn, can be used as a statistical measure of the contribution of the disk lenses and bulge lenses at different depths. The spectra of the microlensed sources provide a unique probe to derive the radial velocities of a sample which lies preferentially at the far side of the Galactic bulge. The radial velocities, coupled with the microlensing time scales, can thus be useful in studying the 3-dimensional kinematics of the Galactic bulge.Comment: 35 pages, 12 figures, Major revisions, Accepted for publication in Ap

Epidemiology of Cryptococcus gattii, British Columbia, Canada, 1999–2007

Incidence is high, but the predominant strain does not seem to cause greater illness or death than do other strains

HST-COS Observations of Hydrogen, Helium, Carbon and Nitrogen Emission from the SN 1987A Reverse Shock

We present the most sensitive ultraviolet observations of Supernova 1987A to date. Imaging spectroscopy from the Hubble Space Telescope-Cosmic Origins Spectrograph shows many narrow (dv \sim 300 km/s) emission lines from the circumstellar ring, broad (dv \sim 10 -- 20 x 10^3 km/s) emission lines from the reverse shock, and ultraviolet continuum emission. The high signal-to-noise (> 40 per resolution element) broad LyA emission is excited by soft X-ray and EUV heating of mostly neutral gas in the circumstellar ring and outer supernova debris. The ultraviolet continuum at \lambda > 1350A can be explained by HI 2-photon emission from the same region. We confirm our earlier, tentative detection of NV \lambda 1240 emission from the reverse shock and we present the first detections of broad HeII \lambda1640, CIV \lambda1550, and NIV] \lambda1486 emission lines from the reverse shock. The helium abundance in the high-velocity material is He/H = 0.14 +/- 0.06. The NV/H-alpha line ratio requires partial ion-electron equilibration (T_{e}/T_{p} \approx 0.14 - 0.35). We find that the N/C abundance ratio in the gas crossing the reverse shock is significantly higher than that in the circumstellar ring, a result that may be attributed to chemical stratification in the outer envelope of the supernova progenitor. The N/C abundance ratio may have been stratified prior to the ring expulsion, or this result may indicate continued CNO processing in the progenitor subsequent to the expulsion of the circumstellar ring.Comment: 12 pages, 8 figures. ApJ - accepte

Human spermbots for patient-representative 3D ovarian cancer cell treatment

Cellular micromotors are attractive for locally delivering high concentrations of drug, and targeting hard-to-reach disease sites such as cervical cancer and early ovarian cancer lesions by non-invasive means. Spermatozoa are highly efficient micromotors perfectly adapted to traveling up the female reproductive system. Indeed, bovine sperm-based micromotors have shown potential to carry drugs toward gynecological cancers. However, due to major differences in the molecular make-up of bovine and human sperm, a key translational bottleneck for bringing this technology closer to the clinic is to transfer this concept to human material. Here, we successfully load human sperm with Doxorubicin (DOX) and perform treatment of 3D cervical cancer and patient-representative ovarian cancer cell cultures, resulting in strong anticancer cell effects. Additionally, we define the subcellular localization of the chemotherapeutic drug within human sperm, using high-resolution optical microscopy. We also assess drug effects on sperm motility and viability over time, employing sperm samples from healthy donors as well as assisted reproduction patients. Finally, we demonstrate guidance and release of human drug-loaded sperm onto cancer tissues using magnetic microcaps, and show the sperm microcap loaded with a second anticancer drug, camptothecin (CPT), which unlike DOX is not suitable for directly loading into sperm due to its hydrophobic nature. This co-drug delivery approach opens up novel targeted combinatorial drug therapies for future applications. © 2020 The Royal Society of Chemistry

Biodistribution PET/CT study of hemoglobin-DFO-89Zr complex in healthy and lung tumor-bearing mice

Proteins, as a major component of organisms, are considered the preferred biomaterials for drug delivery vehicles. Hemoglobin (Hb) has been recently rediscovered as a potential drug carrier, but its use for biomedical applications still lacks extensive investigation. To further explore the possibility of utilizing Hb as a potential tumor targeting drug carrier, we examined and compared the biodistribution of Hb in healthy and lung tumor-bearing mice, using for the first time 89Zr labelled Hb in a positron emission tomography (PET) measurement. Hb displays a very high conjugation yield in its fast and selective reaction with the maleimide-deferoxamine (DFO) bifunctional chelator. The high-resolution X-ray structure of the Hb-DFO complex demonstrated that cysteine β93 is the sole attachment moiety to the αβ-protomer of Hb. The Hb-DFO complex shows quantitative uptake of 89Zr in solution as determined by radiochromatography. Injection of 0.03 mg of Hb-DFO-89Zr complex in healthy mice indicates very high radioactivity in liver, followed by spleen and lungs, whereas a threefold increased dosage results in intensification of PET signal in kidneys and decreased signal in liver and spleen. No difference in biodistribution pattern is observed between naïve and tumor-bearing mice. Interestingly, the liver Hb uptake did not decrease upon clodronate-mediated macrophage depletion, indicating that other immune cells contribute to Hb clearance. This finding is of particular interest for rapidly developing clinical immunology and projects aiming to target, label or specifically deliver agents to immune cells

Trend following, risk parity and momentum in commodity futures

We show that combining momentum and trend following strategies for individual commodity futures can lead to portfolios which offer attractive risk adjusted returns which are superior to simple momentum strategies; when we expose these returns to a wide array of sources of systematic risk we find that robust alpha survives. Experimenting with risk parity portfolio weightings has limited impact on our results though in particular is beneficial to long–short strategies; the marginal impact of applying trend following methods far outweighs momentum and risk parity adjustments in terms of risk-adjusted returns and limiting downside risk. Overall this leads to an attractive strategy for investing in commodity futures and emphasises the importance of trend following as an investment strategy in the commodity futures context