Copper-based Dye-sensitized Solar Cells with Quasi-Solid Nano Cellulose Composite Electrolytes

The study presented describes the preparation of solvent-free nano composite gel electrolytes in combination with  copper(I)-based dye-sensitized solar cells (DSSCs). The electrolytes comprise poly(ethylene oxide) (PEO) and cellulose nano crystals (CNCs) and an I 3 – /I – redox shuttle. The quasi-solid-state DSSCs show increased photoconversion performance with increased amount of CNC in the electrolyte. DSSC performances measured on the day that the devices are fabricated show that when the electrolyte is composed of 80% CNC, a cell efficiency of 1.09% is reached compared to 1.16% using a standard liquid I 3 – /I – electrolyte. DSSCs containing the nano composites and the copper(I)-based dye show robust stability over time, and after 60 days, DSSCs with the PEO/CNC/I 3 – /I – electrolyte outperform those containing the liquid electrolyt

Quality and efficiency of statin prescribing across countries with a special focus on South Africa : findings and future implications

Statins are recommended first-line treatment for hyperlipidemia, with published studies suggesting limited differences between them. However, there are reports of under-dosing. South Africa has introduced measures to enhance generic utilization. Part one documents prescribed doses of statins in 2011. Part two determines the extent of generics versus originator and single-sourced statins in 2011 and their costs. Results: Underdosing of simvastatin in 2011 with average prescribed dose of 23.7 mg; however, not for atorvastatin (20.91 mg) or rosuvastatin (15.02 mg). High utilization of generics versus originators at 93–99% for atorvastatin and simvastatin, with limited utilization of single-sourced statins (22% of total statins – defined daily dose basis), mirroring Netherlands, Sweden and UK. Generics priced 33–51% below originator prices. Discussion: Opportunity to increase simvastatin dosing through education, prescribing targets and incentives. Opportunity to lower generic prices with generic simvastatin 96–98% below single-sourced prices in some European countries

It is important that the process goes quickly, isn't it?” A qualitative multi-country study of colorectal or lung cancer patients’ narratives of the timeliness of diagnosis and quality of care

Purpose: The emphasis on early diagnosis to improve cancer survival has been a key factor in the development of cancer pathways across Europe. The aim of this analysis was to explore how the emphasis on early diagnosis and timely treatment is reflected in patient's accounts of care, from the first suspicion of colorectal or lung cancer to their treatment in Denmark, England and Sweden. Method: We recruited 155 patients in Denmark, England and Sweden who were within six months of being diagnosed with lung or colorectal cancer. Data were collected via semi-structured narrative interviews and analysed using a thematic approach. Results: Participants’ accounts of quality of care were closely related to how quickly (or not) diagnosis, treatment and/or healthcare processes went. Kinetic metaphors as a description of care (such as treadmill) could be interpreted positively as participants were willing to forgo some degree of control and accept disruption to their lives to ensure more timely care. Drawing on wider cultural expectations of the benefits of diagnosing and treating cancer quickly, some participants were concerned that the waiting times between interventions might allow time for the cancer to grow. Conclusions: Initiatives emphasising the timeliness of diagnosis and treatment are reflected in the ways some patients experience their care. However, these accounts were open to further contextualisation about what speed of healthcare processes meant for evaluating the quality of their care. Healthcare professionals could therefore be an important patient resource in providing reassurance and support about the timeliness of diagnosis or treatment

mRNA expression and localization of bNOS, eNOS and iNOS in human cervix at preterm and term labour

BACKGROUND: Preterm birth is the primary cause of the neonatal mortality and morbidity. There will be no preterm birth without a cervical softening. Nitric oxide (NO) is shown to be a mediator of term cervical ripening. The aim of this study was to investigate mRNA expression of the three isomers of NO synthases (NOS) and to identify them by immunohistochemistry in the human cervix at preterm birth compared to term. METHODS: The three isomers of NOS- inducible (iNOS), endothelial (eNOS) and neuronal (bNOS) – were investigated in the human cervix. The expression of mRNA was determined using Real-Time Multiplex RT-PCR. The localisation of synthases in the cervical tissue was analysed using immunohistochemistry. Cervical biopsies were obtained from 4 groups of women without clinical signs of infection: preterm (PTL), term labour (TL), preterm not in labour (PTnotL) and term not in labour (TnotL) patients. One-Way ANOVA, Kruskal-Wallis, Student t-test or Mann-Whitney test were applied as appropriate to determine statistically significant differences among the groups. RESULTS: Patients in preterm labour had significantly (p < 0.01) higher mRNA levels of all the three NOS isomers compared to those in term labour. Women not in labour, irrespective of gestational age, thus with unripe cervices, had significantly lower eNOS mRNA levels compared to those in labour (p < 0.01). Immunoreactivity for all three NO synthases was observed in each examined sample in all groups. The bNOS staining was the most prominent. CONCLUSION: The mRNA levels were higher in the preterm labour group compared to the women at term labour. The significant increase of the eNOS mRNA expression, from the unripe to the favourable cervical state during labour, may indicate a role of eNOS and supports the role of NO in the cervical ripening process. All the three synthases were identified by immunohistochemistry in all the groups of study

Predicting the effect of prandial stage and particle size on absorption of ODM-204.

The prediction of absorption properties plays a key role in formulation development when the compound under development shows poor solubility and its absorption is therefore presumed to be solubility limited. In our work, we combined and compared data obtained from in vitro dissolution tests, transit intestinal model studies (TIM -1) and physiologically based pharmacokinetic modelling. Our aim was to determine the ability of these methods to predict performance of poorly soluble lipophilic weak base in vivo. The validity of the predictive methods was evaluated against the in vivo clinical pharmacokinetic (PK) data obtained after administration of the first test formulation, Tl. The aim of our study was to utilize the models in evaluating absorption properties of the second test formulation, T2, which has not yet been clinically administered. The compound in the studies was ODM-204, which is a novel, orally administered, investigational, nonsteroidal dual inhibitor of CYP17A1 and androgen receptor. Owing to its physicochemical properties ODM-204 is prone to low or variable bioavailability. The models examined provided congruent data on dose dependent absorption, food effect at a dose of 200 mg and on the effect of API (active pharmaceutical ingredient) particle size on absorption. Our study shows that the predictive tools of in vitro dissolution, TIM-1 system and the PBPK (physiologically based pharmacokinetic) simulation, showed predictive power of different mechanisms of bioavailability and together provided valuable information for decision making.Peer reviewe

The structure of human dermatan sulfate epimerase 1 emphasizes the importance of C5 epimerization of glucuronic acid in higher organisms

Dermatan sulfate epimerase 1 DS epi1, EC 5.1.3.19 catalyzes the conversion of D glucuronic acid to L iduronic acid on the polymer level, a key step in the biosynthesis of the glycosaminoglycan dermatan sulfate. Here, we present the first crystal structure of the catalytic domains of DS epi1, solved at 2.4 resolution, as well as a model of the full length luminal protein obtained by a combination of macromolecular crystallography and targeted cross linking mass spectrometry. Based on docking studies and molecular dynamics simulations of the protein structure and a chondroitin substrate, we suggest a novel mechanism of DS epi1, involving a His double Tyr motif. Our work uncovers detailed information about the domain architecture, active site, metal coordinating center and pattern of N glycosylation of the protein. Additionally, the structure of DS epi1 reveals a high structural similarity to proteins from several families of bacterial polysaccharide lyases. DS epi1 is of great importance in a range of diseases, and the structure provides a necessary starting point for design of active site inhibitor

Superfamily Assignments for the Yeast Proteome through Integration of Structure Prediction with the Gene Ontology

Saccharomyces cerevisiae is one of the best-studied model organisms, yet the three-dimensional structure and molecular function of many yeast proteins remain unknown. Yeast proteins were parsed into 14,934 domains, and those lacking sequence similarity to proteins of known structure were folded using the Rosetta de novo structure prediction method on the World Community Grid. This structural data was integrated with process, component, and function annotations from the Saccharomyces Genome Database to assign yeast protein domains to SCOP superfamilies using a simple Bayesian approach. We have predicted the structure of 3,338 putative domains and assigned SCOP superfamily annotations to 581 of them. We have also assigned structural annotations to 7,094 predicted domains based on fold recognition and homology modeling methods. The domain predictions and structural information are available in an online database at http://rd.plos.org/10.1371_journal.pbio.0050076_01

Soft and rigid core latex nanoparticles prepared by RAFT-mediated surfactant-free emulsion polymerization for cellulose modification – a comparative study

Latex nanoparticles comprising cationically charged coronas and hydrophobic cores with different glass transition temperatures (Tg) have been prepared by surfactant-free, RAFT-mediated emulsion polymerization, where the particles form through a polymerization-induced self-assembly (PISA) type mechanism. Poly(2-dimethylaminoethyl methacrylate-co-methacrylic acid) (P(DMAEMA-co-MAA)) was utilized as a hydrophilic macroRAFT agent for the polymerization of methyl methacrylate (MMA) or n-butyl methacrylate (nBMA), respectively, resulting in two different latexes, with either a core of high (PMMA) or low (PnBMA) Tg polymer. By varying the molar mass of the hydrophobic block, latexes of different sizes were obtained (DHca. 40–120 nm). The adsorption of the latexes to cellulose model surfaces and cellulose nanofibrils (CNF) was studied using quartz crystal microbalance with dissipation monitoring (QCM-D). The surfaces with adsorbed PnBMA latexes yielded hydrophobic surfaces both before and after annealing, whereas surfaces with adsorbed PMMA latex became hydrophobic only after annealing, clearly showing the influence of the Tg of the core. The latexes were also used to modify macroscopic cellulose in the form of filter papers. Similar to the CNF surfaces, no annealing was required to achieve hydrophobic surfaces with PnBMA latexes. Finally, nanocomposites of CNF and the polymer nanoparticles were prepared through a one-pot mixing procedure. It was found that the largest synthesized PMMA latex (120 nm) facilitated a more strainable CNF network at 50% relative humidity, with a nearly 200% increase in strain at break compared to the neat CNF reference film as well as to the composite films with PnBMA latexes or to the smaller sized PMMA latexes. This difference was attributed to the spherical shape and rigidity of the large PMMA latex nanoparticles during composite formation. This highly interesting result should indeed be considered in the future design of novel biocomposites.</p

Improving the managed introduction of new medicines : sharing experiences to aid authorities across Europe

The 3-day course on the managed introduction of new drugs was organised by the Piperska group together with the Agency for Health Technology Assessment and Tariff System (AOTMiT) and WHO Europe to share experiences and case histories among health authority and health insurance company personnel, academics and those from commercial organisations from across Europe on potential ways to optimise the managed entry of new medicines. This starts pre-launch with horizon scanning and budgeting, then peri-launch including critical drug evaluation, and finally post launch including monitoring prescribing of new medicines against agreed guidance and indicators. There were also discussions on issues regarding managed entry schemes and procurement strategies including biosimilars

Bias-voltage dependence of the magneto-resistance in ballistic vacuum tunneling: Theory and application to planar Co(0001) junctions

Motivated by first-principles results for jellium and by surface-barrier shapes that are typically used in electron spectroscopies, the bias voltage in ballistic vacuum tunneling is treated in a heuristic manner. The presented approach leads in particular to a parameterization of the tunnel-barrier shape, while retaining a first-principles description of the electrodes. The proposed tunnel barriers are applied to Co(0001) planar tunnel junctions. Besides discussing main aspects of the present scheme, we focus in particular on the absence of the zero-bias anomaly in vacuum tunneling.Comment: 19 pages with 8 figure