Some Understanding of Fischer-Tropsch Synthesis from Density Functional Theory Calculations

The combination of density functional theory (DFT) calculations and kinetic analyses is a very useful approach to study surface reactions in heterogeneous catalysis. The present paper reviews some recent work applying this approach to Fischer-Tropsch (FT) synthesis. Emphasis is placed on the following fundamental issues in FT synthesis: (i) reactive sites for both hydrogenation and C-C coupling reactions; (ii) reaction mechanisms including carbene mechanism, CO-insertion mechanism and hydroxyl-carbene mechanism; (iii) selectivity with a focus on CH(4) selectivity, alpha-olefin selectivity and chain growth probability; and (iv) activity.

A Temperature-Monitoring Vaginal Ring for Measuring Adherence

Background

Product adherence is a pivotal issue in the development of effective vaginal microbicides to reduce sexual transmission of HIV. To date, the six Phase III studies of vaginal gel products have relied primarily on self-reporting of adherence. Accurate and reliable methods for monitoring user adherence to microbicide-releasing vaginal rings have yet to be established.

Methods

A silicone elastomer vaginal ring prototype containing an embedded, miniature temperature logger has been developed and tested in vitro and in cynomolgus macaques for its potential to continuously monitor environmental temperature and accurately determine episodes of ring insertion and removal.

Results

In vitro studies demonstrated that DST nano-T temperature loggers encapsulated in medical grade silicone elastomer were able to accurately and continuously measure environmental temperature. The devices responded quickly to temperature changes despite being embedded in different thickness of silicone elastomer. Prototype vaginal rings measured higher temperatures compared with a subcutaneously implanted device, showed high sensitivity to diurnal fluctuations in vaginal temperature, and accurately detected periods of ring removal when tested in macaques.

Conclusions

Vaginal rings containing embedded temperature loggers may be useful in the assessment of product adherence in late-stage clinical trials.

Microneedle characterisation: the need for universal acceptance criteria and GMP specifications when moving towards commercialisation

With interest in microneedles as a novel drug transdermal delivery system increasing rapidly since the late 1990s (Margetts and Sawyer Contin Educ Anaesthesia Crit Care Pain. 7(5):171-76, 2007), a diverse range of microneedle systems have been fabricated with varying designs and dimensions. However, there are still very few commercially available microneedle products. One major issue regarding microneedle manufacture on an industrial scale is the lack of specific quality standards for this novel dosage form in the context of Good Manufacturing Practice (GMP). A range of mechanical characterisation tests and microneedle insertion analysis techniques are used by researchers working on microneedle systems to assess the safety and performance profiles of their various designs. The lack of standardised tests and equipment used to demonstrate microneedle mechanical properties and insertion capability makes it difficult to directly compare the in use performance of candidate systems. This review highlights the mechanical tests and insertion analytical techniques used by various groups to characterise microneedles. This in turn exposes the urgent need for consistency across the range of microneedle systems in order to promote innovation and the successful commercialisation of microneedle products.

Comparative analysis of Klebsiella pneumoniae genomes identifies a phospholipase D family protein as a novel virulence factor

BACKGROUND: Klebsiella pneumoniae strains are pathogenic to animals and humans, in which they are both a frequent cause of nosocomial infections and a re-emerging cause of severe community-acquired infections. K. pneumoniae isolates of the capsular serotype K2 are among the most virulent. In order to identify novel putative virulence factors that may account for the severity of K2 infections, the genome sequence of the K2 reference strain Kp52.145 was determined and compared to two K1 and K2 strains of low virulence and to the reference strains MGH 78578 and NTUH-K2044.

RESULTS: In addition to diverse functions related to host colonization and virulence encoded in genomic regions common to the four strains, four genomic islands specific for Kp52.145 were identified. These regions encoded genes for the synthesis of colibactin toxin, a putative cytotoxin outer membrane protein, secretion systems, nucleases and eukaryotic-like proteins. In addition, an insertion within a type VI secretion system locus included sel1 domain containing proteins and a phospholipase D family protein (PLD1). The pld1 mutant was avirulent in a pneumonia model in mouse. The pld1 mRNA was expressed in vivo and the pld1 gene was associated with K. pneumoniae isolates from severe infections. Analysis of lipid composition of a defective E. coli strain complemented with pld1 suggests an involvement of PLD1 in cardiolipin metabolism.

CONCLUSIONS: Determination of the complete genome of the K2 reference strain identified several genomic islands comprising putative elements of pathogenicity. The role of PLD1 in pathogenesis was demonstrated for the first time and suggests that lipid metabolism is a novel virulence mechanism of K. pneumoniae.

A novel scalable manufacturing process for the production of hydrogel-forming microneedle arrays

A novel manufacturing process for fabricating microneedle arrays (MN) has been designed and evaluated. The prototype is able to successfully produce 14 × 14 MN arrays and is easily capable of scale-up, enabling the transition from laboratory to industry and subsequent commercialisation. The method requires the custom design of metal MN master templates to produce silicone MN moulds using an injection moulding process. The MN arrays produced using this novel method was compared with centrifugation, the traditional method of producing aqueous hydrogel-forming MN arrays. The results proved that there was negligible difference between either methods, with each producing MN arrays with comparable quality. Both types of MN arrays can be successfully inserted in a skin simulant. In both cases the insertion depth was approximately 60% of the needle length and the height reduction after insertion was in both cases approximately 3%.

A design strategy of large grain lithium-rich layered oxides for lithium-ion batteries cathode

Li-rich materials are considered the most promising for Li-ion battery cathodes, as high capacity can be achieved. However, poor cycling stability is a critical drawback that leads to poor capacity retention. Here a strategy is used to synthesize a large-grain lithium-rich layered oxides to overcome this difficulty without sacrificing rate capability. This material is designed with micron scale grain with a width of about 300 nm and length of 1-3 μm. This unique structure has a better ability to overcome stress-induced structural collapse caused by Li-ion insertion/extraction and reduce the dissolution of Mn ions, which enable a reversible and stable capacity. As a result, this cathode material delivered a highest discharge capacity of around 308 mAh g^-1 at a current density of 30 mA g^-1 with retention of 88.3% (according to the highest discharge capacity) after 100 cycles, 190 mAh g^-1 at a current density of 300 mA g^-1 and almost no capacity fading after 100 cycles. Therefore, Lithium-rich material of large-grain structure is a promising cathode candidate in Lithium-ion batteries with high capacity and high cycle stability for application. This strategy of large grain may furthermore open the door to synthesize the other complex architectures for various applications.

Toxicity of chlorobenzenes to a lux-marked terrestrial bacterium, Pseudomonas fluorescens

Insertion of lux genes, encoding for bioluminescence in naturally bioluminescent marine bacteria, into the genome of Pseudomonas fluorescens resulted in a bioluminescent strain of this terrestrial bacterium. The lux- marked bacterium was used to toxicity test the chlorobenzene series. By correlating chlorobenzenes 50% effective concentration (EC50) values against physiochemical parameters, the physiochemical properties of chlorobenzenes that elicit toxic responses were investigated. The results showed that the more chlorinated the compounds, the more toxic they were to lux-marked P. fluorescens. Furthermore, it was shown that the more symmetrical the compound, the greater its toxicity to P. fluorescens. In general, the toxicity of a chlorobenzene was inversely proportional to its solubility (S) and directly proportional to its lipophilicity (K(ow). By correlating lux- marked P. fluorescens EC50 values, determined for chlorobenzenes, with toxicity values determined using Pimephales promelas (fathead minnow), Cyclotella meneghiniana (diatom), and Vibrio fischeri (marine bacterium), it was apparent that lux-marked P. fluorescens correlated well with freshwater species such as the diatoms and fathead minnow but not with the bioluminescent marine bacterium V. fischeri. The implications of these findings are that a terrestrial bacterium such as P. fluorescens should be used for toxicity testing of soils and freshwaters rather than the marine bacterium V. fischeri.

Super suburbia: developing resilience by closing resource cycles in North Belfast

Sustainability can be described as having three interlinked strands, known as the ‘trias energetica’, without which resilience is difficult to achieve. These strands are environmental, social and economic: and if taken as indicators, the suburbs of North Belfast are very poorly performing indeed. Places such as Ligoneal and Glen Cairn have poor housing stock energetically, and also little economic activity. This paper describes propositional work completed by Queens University and Belfast City Council as part of the UK’s Technology Strategy Board’s Future Cities Programme, which aimed to develop new synergies in these neighbourhoods by the insertion of closed cycle economies.

By utilising a research by design methodology, the paper develops a process-based and phased design to develop a new emergent form to these neighbourhoods, one in which new productive systems are embedded into the city, at a small-scales. These include a peak-load hydro-electric project in Ligoneal; a productive landscape in Glen Cairn and a city-wide energy refurbishment utilising neighbourhood waste streams.

These designs allow for a roadmap for development to be created that could change the modus operandi of an area over a relatively short period of time, and show that even modest investments of productive technologies at a local scale could fundamentally change the form and the economic and environmental operation of the city in the future, and create a new resilient city, one that can be less externally dependent and more socially just.

DEX: self-healing expanders

Improving composite damage modelling through automatic placement of cohesive elements

Numerous experimental studies of damage in composite laminates have shown that intralaminar (in-plane) matrix cracks lead to interlaminar delamination (out-of-plane) at ply interfaces. The smearing of in-plane cracks over a volume, as a consequence of the use of continuum damage mechanics, does not always effectively capture the full extent of the interaction between the two failure mechanisms. A more accurate representation is obtained by adopting a discrete crack approach via the use of cohesive elements, for both in-plane and out-of-plane damage. The difficulty with cohesive elements is that their location must be determined a priori in order to generate the model; while ideally the position of the crack migration, and more generally the propagation path, should be obtained as part of the problem’s solution. With the aim of enhancing current modelling capabilities with truly predictive capabilities, a concept of automatic insertion of interface elements is utilized. The consideration of a simple traction criterion in relation to material strength, evaluated at each node of the model (or of the regions of the model where it is estimated cracks might form), allows for the determination of initial crack location and subsequent propagation by the insertion of cohesive elements during the course of the analysis. Several experimental results are modelled using the commercial package ABAQUS/Standard with an automatic insertion subroutine developed in this work, and the results are presented to demonstrate the capabilities of this technique.

A facile system to evaluate in vitro drug release from dissolving microneedle arrays

The use of biological tissues in the in vitro assessments of dissolving (?) microneedle (MN) array mechanical strength and subsequent drug release profiles presents some fundamental difficulties, in part due to inherent variability of the biological tissues employed. As a result, these biological materials are not appropriate for routine used in industrial formulation development or quality control (QC) tests. In the present work a facile system using Parafilm M® (PF) to test drug permeation performance using dissolving MN arrays is proposed. Dissolving MN arrays containing 196 needles (600 μm needle height) were inserted into a single layer of PF and a hermetic “pouch” was created including the array inside. The resulting system was placed in a dissolution bath and the release of model molecules was evaluated. Different MN formulations were tested using this novel setup, releasing between 40 and 180 µg of their cargos after 6 hours. The proposed system is a more realistic approach for MN testing than the typical performance test described in the literature for conventional transdermal patches. Additionally, the use of PF membrane was tested either in the hermetic “pouch” and using Franz Cell methodology yielding comparable release curves. Microscopy was used in order to ascertain the insertion of the different MN arrays in the PF layer. The proposed system appears to be a good alternative to the use of Franz cells in order to compare different MN formulations. Given the increasing industrial interest in MN technology, the proposed system has potential as a standardised drug/active agent release test for quality control purposes.

Cement As a Waste Form for Nuclear Fission Products: The Case of 90Sr and Its Daughters

One of the main challenges faced by the nuclear industry is the long-term confinement of nuclear waste. Because it is inexpensive and easy to manufacture, cement is the material of choice to store large volumes of radioactive materials, in particular the low-level medium-lived fission products. It is therefore of utmost importance to assess the chemical and structural stability of cement containing radioactive species. Here, we use ab initio calculations based on density functional theory (DFT) to study the effects of ⁹⁰Sr insertion and decay in C-S-H (calcium-silicate-hydrate) in order to test the ability of cement to trap and hold this radioactive fission product and to investigate the consequences of its β-decay on the cement paste structure. We show that ⁹⁰Sr is stable when it substitutes the Ca²⁺ ions in C-S-H, and so is its daughter nucleus ⁹⁰Y after β-decay. Interestingly, ⁹⁰Zr, daughter of ⁹⁰Y and final product in the decay sequence, is found to be unstable compared to the bulk phase of the element at zero K but stable when compared to the solvated ion in water. Therefore, cement appears as a suitable waste form for ⁹⁰Sr storage.

Methylene Blue-Loaded Dissolving Microneedles: Potential Use in Photodynamic Antimicrobial Chemotherapy of Infected Wounds

Photodynamic therapy involves delivery of a photosensitising drug that is activated by light of a specific wavelength, resulting in generation of highly reactive radicals. This activated species can cause destruction of targeted cells. Application of this process for treatment of microbial infections has been termed "photodynamic antimicrobial chemotherapy" (PACT). In the treatment of chronic wounds, the delivery of photosensitising agents is often impeded by the presence of a thick hyperkeratotic/necrotic tissue layer, reducing their therapeutic efficacy. Microneedles (MNs) are an emerging drug delivery technology that have been demonstrated to successfully penetrate the outer layers of the skin, whilst minimising damage to skin barrier function. Delivering photosensitising drugs using this platform has been demonstrated to have several advantages over conventional photodynamic therapy, such as, painless application, reduced erythema, enhanced cosmetic results and improved intradermal delivery. The aim of this study was to physically characterise dissolving MNs loaded with the photosensitising agent, methylene blue and assess their photodynamic antimicrobial activity. Dissolving MNs were fabricated from aqueous blends of Gantrez(®) AN-139 co-polymer containing varying loadings of methylene blue. A height reduction of 29.8% was observed for MNs prepared from blends containing 0.5% w/w methylene blue following application of a total force of 70.56 N/array. A previously validated insertion test was used to assess the effect of drug loading on MN insertion into a wound model. Staphylococcus aureus, Escherichia coli and Candida albicans biofilms were incubated with various methylene blue concentrations within the range delivered by MNs in vitro (0.1-2.5 mg/mL) and either irradiated at 635 nm using a Paterson Lamp or subjected to a dark period. Microbial susceptibility to PACT was determined by assessing the total viable count. Kill rates of >96%, were achieved for S. aureus and >99% for E. coli and C. albicans with the combination of PACT and methylene blue concentrations between 0.1 and 2.5 mg/mL. A reduction in the colony count was also observed when incorporating the photosensitiser without irradiation, this reduction was more notable in S. aureus and E. coli strains than in C. albicans.

Hydrogel-Forming Microneedle Arrays Allow Detection of Drugs and Glucose In Vivo: Potential for Use in Diagnosis and Therapeutic Drug Monitoring

We describe, for the first time the use of hydrogel-forming microneedle (MN) arrays for minimally-invasive extraction and quantification of drug substances and glucose from skin in vitro and in vivo. MN prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) (11.1% w/w) and poly(ethyleneglycol) 10,000 daltons (5.6% w/w) and crosslinked by esterification swelled upon skin insertion by uptake of fluid. Post-removal, theophylline and caffeine were extracted from MN and determined using HPLC, with glucose quantified using a proprietary kit. In vitro studies using excised neonatal porcine skin bathed on the underside by physiologically-relevant analyte concentrations showed rapid (5 min) analyte uptake. For example, mean concentrations of 0.16 μg/mL and 0.85 μg/mL, respectively, were detected for the lowest (5 μg/mL) and highest (35 μg/mL) Franz cell concentrations of theophylline after 5 min insertion. A mean concentration of 0.10 μg/mL was obtained by extraction of MN inserted for 5 min into skin bathed with 5 μg/mL caffeine, while the mean concentration obtained by extraction of MN inserted into skin bathed with 15 μg/mL caffeine was 0.33 μg/mL. The mean detected glucose concentration after 5 min insertion into skin bathed with 4 mmol/L was 19.46 nmol/L. The highest theophylline concentration detected following extraction from a hydrogel-forming MN inserted for 1 h into the skin of a rat dosed orally with 10 mg/kg was of 0.363 μg/mL, whilst a maximum concentration of 0.063 μg/mL was detected following extraction from a MN inserted for 1 h into the skin of a rat dosed with 5 mg/kg theophylline. In human volunteers, the highest mean concentration of caffeine detected using MN was 91.31 μg/mL over the period from 1 to 2 h post-consumption of 100 mg Proplus® tablets. The highest mean blood glucose level was 7.89 nmol/L detected 1 h following ingestion of 75 g of glucose, while the highest mean glucose concentration extracted from MN was 4.29 nmol/L, detected after 3 hours skin insertion in human volunteers. Whilst not directly correlated, concentrations extracted from MN were clearly indicative of trends in blood in both rats and human volunteers. This work strongly illustrates the potential of hydrogel-forming MN in minimally-invasive patient monitoring and diagnosis. Further studies are now ongoing to reduce clinical insertion times and develop mathematical algorithms enabling determination of blood levels directly from MN measurements.

Fermi level de-pinning of aluminium contacts to n-type germanium using thin atomic layer deposited layers

Fermi-level pinning of aluminium on n-type germanium (n-Ge) was reduced by insertion of a thin interfacial dielectric by atomic layer deposition. The barrier height for aluminium contacts on n-Ge was reduced from 0.7 eV to a value of 0.28 eV for a thin Al2O3 interfacial layer (∼2.8 nm). For diodes with an Al2O3 interfacial layer, the contact resistance started to increase for layer thicknesses above 2.8 nm. For diodes with a HfO2 interfacial layer, the barrier height was also reduced but the contact resistance increased dramatically for layer thicknesses above 1.5 nm.