A perspective on using experiment and theory to identify design principles in dye-sensitized solar cells

Dye-sensitized solar cells (DSCs) have been the subject of wide-ranging studies for many years because of their potential for large-scale manufacturing using roll-to-roll processing allied to their use of earth abundant raw materials. Two main challenges exist for DSC devices to achieve this goal; uplifting device efficiency from the 12 to 14% currently achieved for laboratory-scale ‘hero’ cells and replacement of the widely-used liquid electrolytes which can limit device lifetimes. To increase device efficiency requires optimized dye injection and regeneration, most likely from multiple dyes while replacement of liquid electrolytes requires solid charge transporters (most likely hole transport materials – HTMs). While theoretical and experimental work have both been widely applied to different aspects of DSC research, these approaches are most effective when working in tandem. In this context, this perspective paper considers the key parameters which influence electron transfer processes in DSC devices using one or more dye molecules and how modelling and experimental approaches can work together to optimize electron injection and dye regeneration. This paper provides a perspective that theory and experiment are best used in tandem to study DSC device

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Pharmacokinetic Study of Rucaparib in Patients With Advanced Solid Tumors

The phase 1‐2 study CO‐338‐010 (Study 10; NCT01482715) is evaluating single‐agent rucaparib, a poly(ADP‐ribose) polymerase inhibitor, administered orally to patients with an advanced solid tumor. In the dose escalation phase (Part 1), we characterized the single‐dose and steady‐state pharmacokinetic profiles of rucaparib administered once daily (QD; dose range, 40‐500 mg; n = 16) or twice daily (BID; dose range, 240‐840 mg; n = 30). Across all dosing schedules examined, the plasma exposure of rucaparib was approximately dose proportional; half‐life was approximately 17 hours, and median time to maximum concentration (t_max) ranged from 1.5 to 6.0 hours after a single dose and 1.5 to 4.0 hours following repeated dosing. The steady‐state accumulation ratio ranged from 1.60 to 2.33 following QD dosing and 1.47 to 5.44 following BID dosing. No effect of food on rucaparib pharmacokinetics was observed with a single dose of 40 mg (n = 3) or 300 mg (n = 6). In a phase 2 portion of the study (Part 3), the pharmacokinetic profile of rucaparib was further evaluated at the recommended phase 2 dose of 600 mg BID (n = 26). The mean (coefficient of variation) steady‐state maximum concentration (C_max) and area under the concentration‐time curve from time zero to 12 hours (AUC_0-12h) were 1940 ng/mL (54%) and 16 900 ng ⋅ h/mL (54%), respectively. A high‐fat meal moderately increased rucaparib exposure. The fed‐to‐fasted geometric mean ratios (90% confidence interval [CI]) for AUC_0-24h and C_max were 138% (117%‐162%) and 120% (99.1%‐146%); the median (90%CI) t_max delay was 2.5 (0.5‐4.4) hours

Assessing the efficacy of the healthy eating and lifestyle programme (HELP) compared with enhanced standard care of the obese adolescent in the community: study protocol for a randomized controlled trial

Background: The childhood obesity epidemic is one of the foremost UK health priorities. Childhood obesity tracks into adult life and places individuals at considerable risk for diabetes, cardiovascular disease, liver disease and other morbidities. There is widespread need for paediatric lifestyle programmes as change may be easier to accomplish in childhood than later in life. Study Design/Method: The study will evaluate the management of adolescent obesity by conducting a Medical Research Council complex intervention phase III efficacy randomised clinical trial of the Healthy Eating Lifestyle Programme within primary care. The study tests a community delivered multi-component intervention designed for adolescents developed from best practice as identified by National Institute for Health and Clinical Excellence. The hospital based pilot reduced body mass index and improved health-related quality of life. Subjects will be individually randomised to receiving either the Healthy Eating Lifestyle Programme (12 fortnightly family sessions) or enhanced standard care. Baseline and follow up assessments will be undertaken blind to allocation status. A health economic evaluation is also being conducted. 200 obese young people (13-17 years, body mass index > 98th centile for age and sex) will be recruited from primary care within the greater London area. The primary hypothesis is that a motivational and solution-focused family-based weight management programme delivered over 6 months is more efficacious in reducing body mass index in obese adolescents identified in the community than enhanced standard care. The primary outcome will be body mass index at the end of the intervention, adjusted for baseline body mass index, age and sex. The secondary hypothesis is that the Healthy Eating Lifestyle Programme is more efficacious in improving quality of life and psychological function and reducing waist circumference and cardiovascular risk factors in obese adolescents than enhanced standard care assessed at 6 and 12 months post baseline assessment. Improvement in quality of life predicts on-going lifestyle change and maximises the chances of long-term weight reduction. We will explore whether improvement in QOL may be intermediate on the pathway between the intervention and body mass index change

18F-fluoro-deoxy-glucose focal uptake in very small pulmonary nodules: fact or artifact? Case reports

ABSTRACT: BACKGROUND: F-fluoro-deoxy-glucose (18F-FDG) positron emission tomography integrated/combined with computed tomography (PET-CT) provides the best diagnostic results in the metabolic characterization of undetermined solid pulmonary nodules. The diagnostic performance of 18F-FDG is similar for nodules measuring at least 1 cm and for larger masses, but few data exist for nodules smaller than 1 cm. CASE PRESENTATION: We report five cases of oncologic patients showing focal lung 18F-FDG uptake on PET-CT in nodules smaller than 1 cm. We also discuss the most common causes of 18F-FDG false-positive and false-negative results in the pulmonary parenchyma. In patient 1, contrast-enhanced CT performed 10 days before PET-CT did not show any abnormality in the site of uptake; in patient 2, high-resolution CT performed 1 month after PET showed a bronchiole filled with dense material interpreted as a mucoid impaction; in patient 3, contrast-enhanced CT performed 15 days before PET-CT did not identify any nodules; in patients 4 and 5, contrast-enhanced CT revealed a nodule smaller than 1 cm which could not be characterized. The 18F-FDG uptake at follow-up confirmed the malignant nature of pulmonary nodules smaller than 1 cm which were undetectable, misinterpreted, not recognized or undetermined at contrast-enhanced CT. CONCLUSION: In all five oncologic patients, 18F-FDG was able to metabolically characterize as malignant those nodules smaller than 1 cm, underlining that: 18F-FDG uptake is not only a function of tumor size but it is strongly related to the tumor biology; functional alterations may precede morphologic abnormalities. In the oncologic population, especially in higher-risk patients, PET can be performed even when the nodules are smaller than 1 cm, because it might give an earlier characterization and, sometimes, could guide in the identification of alterations missed on CT

Combinatorial targeting and discovery of ligand-receptors in organelles of mammalian cells

Phage display screening allows the study of functional protein–protein interactions at the cell surface, but investigating intracellular organelles remains a challenge. Here we introduce internalizing-phage libraries to identify clones that enter mammalian cells through a receptor-independent mechanism and target-specific organelles as a tool to select ligand peptides and identify their intracellular receptors. We demonstrate that penetratin, an antennapedia-derived peptide, can be displayed on the phage envelope and mediate receptor-independent uptake of internalizing phage into cells. We also show that an internalizing-phage construct displaying an established mitochondria-specific localization signal targets mitochondria, and that an internalizing-phage random peptide library selects for peptide motifs that localize to different intracellular compartments. As a proof-of-concept, we demonstrate that one such peptide, if chemically fused to penetratin, is internalized receptor-independently, localizes to mitochondria, and promotes cell death. This combinatorial platform technology has potential applications in cell biology and drug development

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO