Crystallisation of Aspirin via Simulated Pulmonary Surfactant Monolayers and Lung-Specific Additives

Pain is a prevalent condition that can have a serious impact upon the socioeconomic function of a population. Numerous methods exist to administer analgesic medication (e.g. aspirin) to the body however inherent drawbacks limit patient acceptability. The inhaled route offers promise to facilitate the administration of medication to the body. Here, we consider the crystallisation behaviour of aspirin, our model therapeutic agent, when in contact with material of relevance to the lung. Thus, our approach aims to better understand the interaction between drug substances and the respiratory tract. Langmuir monolayers composed of a mixed surfactant system were supported on an aqueous subphase containing aspirin (7.5mg/ml). The surfactant film was compressed to either 5mN/m (i.e. inhalation end point) or 50mN/m (i.e. exhalation end point), whilst located within a humid environment for 16 hours. Standard cooling crystallisation procedures were employed to produce control samples. Antisolvent crystallisation in the presence or absence of lung-specific additives was conducted. All samples were analysed via scanning electron microscopy (SEM) and X-ray diffraction (XRD). Drug-surfactant interactions were confirmed via condensed Langmuir isotherms. SEM analysis revealed plate-like morphology. The crystallisation route dictated both the crystal habit and particle size distribution. Dominant reflections were the (100) and (200) aspects. The main modes of interaction were hydrogen bonding, hydrophobic associations and van der Waals forces. Here, we have demonstrated the potential of antisolvent crystallisation with lung-specific additives to achieve control over drug crystal morphology. The approach taken can be applied in respirable formulation engineering

On drug-base incompatibilities during extrudate manufacture and fused deposition 3D printing

Aim: 3D printing can be applied for point-of-care personalized treatment. This study aimed to determine the manufacturability and characteristics of 3D printed, drug loaded implants for alcohol misuse. Materials & methods: Disulfiram was the drug substance used and polylactic acid (PLA) the base material. Implantable devices were designed in silico. Drug and PLA were placed into the extruder to produce a 5% blend at 1.75-mm diameter. Material characterization included differential scanning calorimetry, thermogravimetric analysis plus inverse GC-surface energy analyzer. Results: Implantable constructs from the PLA feedstock were acquired. The extrusion processes had a detrimental effect on the active pharmaceutical ingredient-base blend. differential scanning calorimetry and thermogravimetric analysis analysis indicated drug–base interactions. Thermal history was found to influence inverse GC probe interaction. Conclusion: Drug-base incompatibilities must be considered during 3D printing

Nanoscale phase-engineering of thermal transport with a Josephson heat modulator

Macroscopic quantum phase coherence has one of its pivotal expressions in the Josephson effect [1], which manifests itself both in charge [2] and energy transport [3-5]. The ability to master the amount of heat transferred through two tunnel-coupled superconductors by tuning their phase difference is the core of coherent caloritronics [4-6], and is expected to be a key tool in a number of nanoscience fields, including solid state cooling [7], thermal isolation [8, 9], radiation detection [7], quantum information [10, 11] and thermal logic [12]. Here we show the realization of the first balanced Josephson heat modulator [13] designed to offer full control at the nanoscale over the phase-coherent component of thermal currents. Our device provides magnetic-flux-dependent temperature modulations up to 40 mK in amplitude with a maximum of the flux-to-temperature transfer coefficient reaching 200 mK per flux quantum at a bath temperature of 25 mK. Foremost, it demonstrates the exact correspondence in the phase-engineering of charge and heat currents, breaking ground for advanced caloritronic nanodevices such as thermal splitters [14], heat pumps [15] and time-dependent electronic engines [16-19].Comment: 6+ pages, 4 color figure

Analysis of defect-related inhomogeneous electroluminescence in InGaN/GaN QW LEDs

The inhomogeneous electroluminescence (EL) of InGaN/GaN quantum well light emitting diode structures was investigated in this study. Electroluminescence hyperspectral images showed that inhomogeneities in the form of bright spots exhibited spectrally blue-shifted and broadened emission. Scanning electron microscopy combined with cathodoluminescence (SEM-CL) was used to identify hexagonal pits at the centre of approximately 20% of these features. Scanning transmission electron microscopy imaging with energy dispersive X-ray spectroscopy (STEM-EDX) indicated there may be p-doped AlGaN within the active region caused by the presence of the pit. Weak beam dark-field TEM (WBDF-TEM) revealed the presence of bundles of dislocations associated with the pit, suggesting the surface features which cause the inhomogeneous EL may occur at coalescence boundaries, supported by trends in the number of features observed across the wafer.The European Research Council has provided financial support under the European Community’s Seventh Framework Programme/ ERC grant agreement no. 279361 (MACONS).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.spmi.2016.03.03

A novel missense mutation of bovine lipase maturation factor 1 (LMF1) gene and its association with growth traits

Lipase maturation factor 1 (LMF1) gene is a novel candidate gene in severe hypertriglyceridemia. To detect the polymorphism in LMF1 gene in 804 Chinese cattle, we firstly described the polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP), DNA sequence and PCR-RFLP methods for detecting mutations of LMF1 gene, which affected growth and development in animal. The results showed a novel mutation in exon 4: NC_007326.3: g.27154 T>C, which resulted in a missense mutation within LMF1 protein (p.197 Trp>Arg). Genotype TT was dominant in four breeds, and genotypic frequencies of LMF1 exon 4 AvaI locus were calculated in four populations which agreed with Hardy- Weinberg equilibrium (p > 0.05). The association analysis showed that individuals with genotype TC had greater body weight than those with genotype TT at 12, 18 and 24 months of age in Nanyang cattle (P < 0.05).Key words: Bovine, polymorphism, growth traits, LMF1 gene

Giant energy storage density in PVDF with internal stress engineered polar nanostructures

High power dielectric capacitors with high energy density are needed in order to develop modern electronic and electrical systems, including hybrid vehicles, telecommunication infrastructures and portable electronic devices. Relaxor ferroelectric polymers (RFP) are considered to be the most promising candidates for the next generation of capacitors owing to their relatively high energy storage density. However, the commercialization of RFP capacitors in power systems is hindered by their high cost and low dielectric breakdown strength. In this study, inexpensive, free-standing nano-crystalline (~3.3 nm) poly (vinylidene fluoride) (PVDF) films with high β phase content (~98%), “relaxor-like” ferroelectric behaviour and high breakdown strength (880 kV/mm) were fabricated using the facile Press & Folding (P&F) technique. An internal stress dominated polarization switching model is proposed to explain the origin of the relaxor-like ferroelectric behaviour. The internal stress generated during pressing alters the intermolecular chain distance of the (200) plane of β-PVDF from 4.24 Å in internal stress free films to 4.54 Å in P&F films, corresponding to a tensile strain and residual stress of 7.11% and 142 MPa, respectively. The internal stress acts to partially reverse the polarization on reversal of the applied electric field. This, combined with preferred in-plane orientation of the crystallites, results in a polar nanostructure with high polarization reversibility at high electric fields. A giant discharged energy storage density of 39.8 J/cm3 at 880 kV/mm was achieved for P&F films, which surpasses all previously reported polymer-based materials

Steady-state and equilibrium vortex configurations, transitions, and evolution in a mesoscopic superconducting cylinder

Journals published by the American Physical Society can be found at http://journals.aps.org/A numerical scheme to study the mixed states in a mesoscopic type-II superconducting cylinder is described. Steady-state configurations and transient behavior of the magnetic vortices for various values of the applied magnetic field H are presented. Transitions between different multivortex states as H is changed is demonstrated by contour plots and jumps in the B vs H plot. We evolve a uniformly superconducting initial state using the simplest set of relaxation equations. The results reveal that the system passes through nearly metastable intermediate configurations while seeking the final minimum-energy steady state consistent with the square symmetry of the sample. An efficient scheme to determine the equilibrium vortex configuration in a mesoscopic system at any given applied field, not limited to the symmetry of the system, is devised and demonstrated

Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy

BACKGROUND: Autoimmune retinal degeneration may occur in patients who present with sudden or, less commonly, subacute loss of vision of retinal origin, associated with an abnormal ERG, through the action of autoantibodies against retinal proteins. Often the patients are initially diagnosed with or suspected of having a paraneoplastic retinopathy (PR), such as cancer-associated retinopathy (CAR). However, there is limited information on the occurrence, the specificity of autoantibodies in these patients, and their association with clinical symptoms. METHODS: Sera were obtained from 193 retinopathy patients who presented with clinical symptoms resembling PR or autoimmune retinopathy (AR), including sudden painless loss of vision, typically associated with visual field defects and photopsias, and abnormal rod and/or cone responses on the electroretinogram (ERG). Sera were tested for the presence of anti-retinal autoantibodies by Western blot analysis using proteins extracted from human retina and by immunohistochemistry. Autoantibody titers against recoverin and enolase were measured by ELISA. RESULTS: We identified a higher prevalence of anti-retinal autoantibodies in retinopathy patients. Ninety-one patients' sera (47.1%) showed autoantibodies of various specificities with a higher incidence of antibodies present in retinopathy patients diagnosed with cancer (33/52; 63.5%; p = 0.009) than in retinopathy patients without cancer (58/141; 41.1%). The average age of PR patients was 62.0 years, and that of AR patients was 55.9 years. Autoantibodies against recoverin (p23) were only present in the sera of PR patients, autoantibodies against unknown p35 were more common in patients with AR, while anti-enolase (anti-p46) autoantibodies were nearly equally distributed in the sera of patients with PR and those with AR. In the seropositive patients, the autoantibodies persisted over a long period of time – from months to years. A rebound in anti-recoverin autoantibody titer was found to be associated with exacerbations in visual symptoms but not in the recurrence of cancer. When compared to sera from healthy subjects, autoantibodies against retinal proteins from both groups of patients were cytotoxic to retinal cells, indicating their pathogenic potential. CONCLUSIONS: These studies showed that patients with sudden or subacute, unexplained loss of vision of retinal origin have anti-retinal antibodies in a broad range of specificity and indicate the need for autoantibody screening. Follow-up tests of antibody levels may be useful as a biomarker of disease activity associated with worsening of vision. Moreover, the heterogeneity in autoantibody specificity may explain the variation and complexity of clinical symptoms in retinopathy patients

Increased NBCn1 expression, Na+/HCO3- co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension.

Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na+/HCO3- co-transporter NBCn1 which regulates intracellular pH (pHi). We conducted a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allele is associated with increased SLC4A7 expression level, NBCn1 availability and function as reflected in elevated steady-state pHi and accelerated recovery from intracellular acidosis. However, in the presence of Na+/H+ exchange activity, the SLC4A7 genotypic effect on net base uptake and steady-state pHi persisted only in vascular smooth muscle cells but not endothelial cells. We found no discernable effect of the missense polymorphism resulting in the amino acid substitution Glu326Lys. The finding of a genotypic influence on SLC4A7 expression and pHi regulation in vascular smooth muscle cells provides an insight into the molecular mechanism underlying the association of variation at the SLC4A7 locus with blood pressure

Sequence variation in TgROP7 gene among Toxoplasma gondii isolates from different hosts and geographical regions

Toxoplasma gondii can infect a wide range of hosts including mammals and birds, causing toxoplasmosis which is one of the most common parasitic zoonoses worldwide. The present study examined sequence variation in rhoptry 7 (ROP7) gene among different T. gondii isolates from different hosts and geographical localities. Phylogenetic analysis of the examined T. gondii isolates was conducted using the maximum likelihood (ML) method. Sequence analysis revealed that 60 nucleotide positions were variable in the ROP7 gene sequences among the 19 examined T. gondii isolates, corresponding to sequence variations of 0 to 1.7%, which occurred at the first, second and third codons. Phylogenetic analysis indicated that sequence variation in ROP7 gene was low among the examined T. gondii isolates from different hosts and geographical localities, and that the ROP7 sequence was not suitable as genetic marker for the differentiation of T. gondii isolates. The results of the present study suggest that ROP7 gene may be a suitable vaccine candidate.Key words: Sequence variation, rhoptry 7 (ROP7) gene, Toxoplasma gondii, toxoplasmosis, phylogenetic analysis